PMID- 20348220 TI - The heart rate response to spontaneous arousal from sleep is reduced in children with Down syndrome referred for evaluation of sleep-disordered breathing. AB - Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. Twenty children aged 3-17 yr referred for investigation of sleep-disordered breathing (10 DS, and 10 OSA controls) matched for age and obstructive apnea/hypopnea index underwent routine overnight polysomnography. In addition, 10 nonsnoring controls from the general community were studied. Beat-by-beat HR was analyzed from 15 s pre- to 15 s post-spontaneous arousals and compared between groups using two-way ANOVA with repeated measures. Data are presented as means + or - SE. For both rapid eye movement (REM) and non-REM (NREM), arousals were associated with a significant increase in HR in all groups (peak response NREM: DS, 118 + or - 1% at 3 s; OSA controls, 124 + or - 2% at 4 s; and healthy controls, 125 + or - 3% at 4 s; and peak response REM: DS, 116 + or - 2% at 4 s; OSA controls, 123 + or - 3% at 4 s; and healthy controls, 125 + or - 4 at 4 s; P < 0.001 for all). Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P < 0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA. PMID- 20348221 TI - Parallel resetting of arterial baroreflex control of renal and cardiac sympathetic nerve activities during upright tilt in rabbits. AB - Since humans are under ceaseless orthostatic stress, the mechanisms to maintain arterial pressure (AP) against gravitational fluid shift are important. As one mechanism, it was reported that upright tilt reset baroreflex control of renal sympathetic nerve activity (SNA) to a higher SNA in anesthetized rabbits. In the present study, we tested the hypothesis that upright tilt causes a parallel resetting of baroreflex control of renal and cardiac SNAs in anesthetized rabbits. In anesthetized rabbits (n = 8, vagotomized and aortic denervated) with 0 degrees supine and 60 degrees upright tilt postures, renal and cardiac SNAs were simultaneously recorded while isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg. Upright tilt shifted the reverse-sigmoidal curve of the CSP-SNA relationship to higher SNA similarly in renal and cardiac SNAs. Although upright tilt increased the maximal gain, the response range and the minimum value of SNA, the curves were almost superimposable in these SNAs regardless of postures. Scatter plotting of cardiac SNA over renal SNA during the stepwise changes in CSP was close to the line of identity in 0 degrees supine and 60 degrees upright tilt postures. In addition, upright tilt also shifted the reverse-sigmoidal curve of the CSP-heart rate relationship to a higher heart rate, with increases in the maximal gain and the response range. In conclusion, upright posture caused a resetting of arterial baroreflex control of SNA similarly in renal and cardiac SNAs in anesthetized rabbits. PMID- 20348222 TI - Effects of adiponectin deficiency on structural and metabolic remodeling in mice subjected to pressure overload. AB - Recent data suggest adiponectin, an adipocyte-derived hormone, affects development of heart failure in response to hypertension. Severe short-term pressure overload [1-3 wk of transverse aortic constriction (TAC)] in adiponectin(-/-) mice causes greater left ventricle (LV) hypertrophy than in wild type (WT) mice, but conflicting results are reported regarding LV remodeling, with either increased or decreased LV end diastolic volume compared with WT mice. Here we assessed the effects of prolonged TAC on LV hypertrophy and remodeling. WT and adiponectin(-/-) mice were subjected to TAC and maintained for 6 wk. Regardless of strain, TAC induced similar LV hypertrophy ( approximately 70%) and upregulation of mRNA for heart failure marker genes. However, LV chamber size was dramatically different, with classic LV dilation in WT TAC mice but concentric LV hypertrophy in adiponectin(-/-) mice. LV end diastolic and systolic volumes were lower and ejection fraction higher in adiponectin(-/-) TAC mice compared with WT, indicating that adiponectin deletion prevented LV remodeling and deterioration in systolic function. The activities of marker enzymes of mitochondrial oxidative capacity were reduced in WT TAC mice by approximately 35%, whereas enzyme activities were maintained at sham levels in adiponectin(-/-) TAC mice. In conclusion, in WT mice, long-term pressure overload caused dilated LV hypertrophy accompanied by decreased activity of mitochondrial oxidative enzymes. Although adiponectin deletion did not affect LV hypertrophy, it prevented LV chamber remodeling and preserved mitochondrial oxidative capacity, suggesting that adiponectin plays a permissive role in mediating changes in cardiac structure and metabolism in response to pressure overload. PMID- 20348223 TI - Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes. AB - Studies from animal models suggest that myocardial mitochondrial damage contributes to cardiac dysfunction after burn injury. In this report, we used an ex vivo model of primary cardiomyocyte culture to investigate the mechanisms of burn-induced mitochondrial impairment. Briefly, blood serum was collected from Sprague-Dawley (SD) rats subjected to 40% total body surface area burn and added (10% vol/vol) to primary cardiomyocytes prepared from SD rats. The effect of the burn serum on mitochondrial function and membrane integrity in the myocytes was analyzed. Exposure of myocytes to burn serum doubled the mitochondrial membrane damage measured by two independent assays. This treatment also significantly elevated mitochondrial oxidative stress, indicated by a more than 30% increase in lipid oxidation. Downregulation of mitochondrial antioxidant defense was also evident since the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced by about 30% and 50%, respectively. Burn serum also induced deficiency of mitochondrial metabolism, indicated by a 30% decrease in the activity of cytochrome c oxidase. These mitochondrial dysfunctions appear to be generated by oxidative stress because burn serum induced a significant increase of mitochondrial oxygen species (mtROS) in cardiomyocytes, and pretreatment of cardiomyocytes with the antioxidant N-acetyl cysteine prevented the mitochondrial damages induced by burn serum. Remarkably, the increase in mtROS was abolished by an antibody-mediated blockade of CD14. Furthermore, burn injury-induced mitochondrial damage in cardiomyocytes was prevented in CD14 knockout mice. Taken together, these data suggested that burn injury produces CD14-dependent mitochondrial damage via oxidative stress in myocardium. PMID- 20348224 TI - Intermittent pneumatic leg compressions acutely upregulate VEGF and MCP-1 expression in skeletal muscle. AB - Application of intermittent pneumatic compressions (IPC) is an extensively used therapeutic strategy in vascular medicine, but the mechanisms by which this method works are unclear. We tested the hypothesis that acute application (150 min) of cyclic leg compressions in a rat model signals upregulation of angiogenic factors in skeletal muscle. To explore the impact of different pressures and frequency of compressions, we divided rats into four groups as follows: 120 mmHg (2 s inflation/2 s deflation), 200 mmHg (2 s/2 s), 120 mmHg (4 s/16 s), and control (no intervention). Blood flow and leg oxygenation (study 1) and the mRNA expression of angiogenic mediators in the rat tibialis anterior muscle (study 2) were assessed after a single session of IPC. In all three groups exposed to the intervention, a modest hyperemia (approximately 37% above baseline) between compressions and a slight, nonsignificant increase in leg oxygen consumption (approximately 30%) were observed during IPC. Compared with values in the control group, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein 1 (MCP-1) mRNA increased significantly (P < 0.05) only in rats exposed to the higher frequency of compressions (2 s on/2 s off). Endothelial nitric oxide synthase, matrix metalloproteinase-2, and hypoxia-inducible factor-1alpha mRNA did not change significantly following the intervention. These findings show that IPC application augments the mRNA content of key angiogenic factors in skeletal muscle. Importantly, the magnitude of changes in mRNA expression appeared to be modulated by the frequency of compressions such that a higher frequency (15 cycles/min) evoked more robust changes in VEGF and MCP-1 compared with a lower frequency (3 cycles/min). PMID- 20348225 TI - Tafazzin knockdown causes hypertrophy of neonatal ventricular myocytes. AB - Mutation of the mitochondrial protein tafazzin causes dilated cardiomyopathy in Barth syndrome. We employed an adenovirus as a vector to transfer tafazzin small hairpin RNA (shRNA) into neonatal ventricular myocytes (NVMs) to investigate the effects of tafazzin knockdown. The tafazzin shRNA adenovirus consistently knocked down tafazzin mRNA and lowered cardiolipin while significantly decreasing the production of ATP by the mitochondria. The phosphorylation of AMP-activated protein kinase and mitochondrial density were both increased in tafazzin knockdown NVMs compared with scrambled shRNA controls. When we tested whether tafazzin knockdown causes hypertrophy in vitro, we found that the surface area of NVMs infected with tafazzin shRNA adenovirus was significantly increased, as were the protein synthesis and expression of the hypertrophic marker gene, brain natriuretic peptide. Taken together, our data support the concept that a decreased tafazzin expression causes cardiomyocyte hypertrophy in vitro. PMID- 20348226 TI - Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender. AB - The lungs are now recognized as an active metabolic organ that is a major determinant of the plasma concentrations of the vasoconstrictors endothelin (ET) and ANG II. Several studies have suggested a complex interaction between ET and ANG II in the systemic and coronary vascular beds that is different at rest and during exercise. To date, the interaction between these vasoconstrictor peptides has barely been investigated in relation to the pulmonary vascular bed. Consequently, we investigated the integrated control of pulmonary vasomotor tone by ET and ANG II in 24 chronically instrumented swine (15 female and 9 male) at rest and during graded treadmill exercise. In the systemic circulation, ANG II type 1 (AT(1)) receptor blockade with irbesartan and mixed ET(A)/ET(B) blockade with tezosentan each produced vasodilation. The systemic vasodilator effect of ET(A)/ET(B) blockade was enhanced after AT(1) blockade in female swine, whereas a trend toward an increase was observed in male swine. In the pulmonary circulation, AT(1) receptor blockade had no effect on pulmonary vascular tone in male swine, whereas it resulted in an unexpected increase in pulmonary vasomotor tone in female swine. ET(A)/ET(B) receptor blockade did not result in a decrease in pulmonary vasomotor tone at rest but produced a decrease in vasomotor tone during exercise in both genders. This pulmonary vasodilation by ET(A)/ET(B) receptor blockade was enhanced after prior AT(1) blockade in female swine but not in male swine. In conclusion, in both the systemic and pulmonary circulation of female swine, ANG II inhibits the vasoconstrictor influence of ET. This interaction is gender specific. The observation that plasma ET levels were not altered by AT(1) blockade in either gender suggests that the interaction between these vasoconstrictors occurs locally in the vasculature. PMID- 20348227 TI - Erythrocytes: surveyors as well as purveyors of oxygen? PMID- 20348228 TI - Effect of erythrocyte aggregation and flow rate on cell-free layer formation in arterioles. AB - Formation of a cell-free layer is an important dynamic feature of microcirculatory blood flow, which can be influenced by rheological parameters, such as red blood cell aggregation and flow rate. In this study, we investigate the effect of these two rheological parameters on cell-free layer characteristics in the arterioles (20-60 mum inner diameter). For the first time, we provide here the detailed temporal information of the arteriolar cell-free layer in various rheological conditions to better describe the characteristics of the layer variation. The rat cremaster muscle was used to visualize arteriolar flows, and the extent of aggregation was raised by dextran 500 infusion to levels seen in normal human blood. Our results show that cell-free layer formation in the arterioles is enhanced by a combination of flow reduction and red blood cell aggregation. A positive relation (P < 0.005) was found between mean cell-free layer widths and their corresponding SDs for all conditions. An analysis of the frequency and magnitudes of cell-free layer variation from their mean value revealed that the layer deviated with significantly larger magnitudes into the red blood cell core after flow reduction and dextran infusion (P < 0.05). In accordance, the disparity of cell-free layer width distribution found in opposite radial directions from its mean became greater with aggregation in reduced flow conditions. This study shows that the cell-free layer width in arterioles is dependent on both flow rate and red blood cell aggregability, and that the temporal variations in width are asymmetric with a greater excursion into the red blood cell core than toward the vessel wall. PMID- 20348229 TI - Circadian clock regulates response to pesticides in Drosophila via conserved Pdp1 pathway. AB - Daily rhythms generated by the circadian clock regulate many life functions, including responses to xenobiotic compounds. In Drosophila melanogaster, the circadian clock consists of positive elements encoded by cycle (cyc) and Clock (Clk) and negative elements encoded by period (per) and timeless (tim) genes. The epsilon-isoform of the PAR-domain protein 1 (Pdp1epsilon) transcription factor is controlled by positive clock elements and regulates daily locomotor activity rhythms. Pdp1 target genes have not been identified, and its involvement in other clock output pathways is not known. Mammalian orthologs of Pdp1 have been implicated in the regulation of xenobiotic metabolism; therefore, we asked whether Pdp1 has a similar role in the fly. Using pesticides as model toxicants, we determined that disruption of Pdp1epsilon increased pesticide-induced mortality in flies. Flies deficient for cyc also showed increased mortality, while disruption of per and tim had no effect. Day/night and Pdp1-dependent differences in the expression of xenobiotic-metabolizing enzymes Cyp6a2, Cyp6g1, and alpha-Esterase-7 were observed and likely contribute to impaired detoxification. DHR96, a homolog of constitutive androstane receptor and pregnane X receptor, is involved in pesticide response, and DHR96 expression decreased when Pdp1 was suppressed. Taken together, our data uncover a pathway from the positive arm of the circadian clock through Pdp1 to detoxification effector genes, demonstrating a conserved role of the circadian system in modulating xenobiotic toxicity. PMID- 20348230 TI - Lung damage in mice after inhalation of nanofilm spray products: the role of perfluorination and free hydroxyl groups. AB - Exposures to two commercial nanofilm spray products (NFPs), a floor sealant (NFP 1) and a coating product for tiles (NFP 2), were investigated for airway irritation, airway inflammation, and lung damage in a mouse inhalation model. The particle exposure was characterized by particle number, particle size distribution, and gravimetric analysis. BALB/cJ mice were exposed for 60 min to the aerosolized products at 3.3-60 mg/m(3) (10(5)-10(6) fine particles/cm(3)) measured in the breathing zone of the mice. Lung inflammation and lung damage were assessed by study of bronchoalveolar lavage fluid (BALF) cytology, protein in BALF, and histology. Mass spectral analysis showed that NFP 1 and NFP 2 contained hydrolysates and condensates of a perfluorosilane and alkylsilane, respectively. NFP 1 induced a concentration-dependent decrease of the tidal volume lasting for at least 1 day. Exposure concentrations above 16.1 mg/m(3) (2.1 x 10(6) fine particles/cm(3)) gave rise to significant increases of protein level in BALF and reduced body weight, and histological examination showed atelectasis, emphysema, and hemorrhages. A narrow interval between the no-effect level (16.1 mg/m(3)) and the lethal concentrations (18.4 mg/m(3)) was observed. The alkylsilane-based product (NFP 2) had no effect at the concentrations studied. Experiments with different types of perfluorinated silanes and alkylsiloxanes showed that the toxic effects did not arise solely from the perfluorination. The number of free hydroxyl groups in the silanes/alkylsiloxanes was also critical for the toxicity. PMID- 20348231 TI - 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated suppression of toll-like receptor stimulated B-lymphocyte activation and initiation of plasmacytic differentiation. AB - 2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent suppressor of humoral immunity, disrupting antibody production in response to both T cell-dependent and T cell-independent antigens. Among the cell types required for humoral responses, the B cell is highly, and directly, sensitive to TCDD. B cells become antibody secreting cells via plasmacytic differentiation, a process regulated by several transcription factors, including activator protein-1, B-cell CLL/lymphoma 6 (BCL 6), and B lymphocyte-induced maturation protein 1 (Blimp-1). The overarching conceptual framework guiding experimentation is that TCDD disrupts plasmacytic differentiation by altering the expression or activity for upstream regulators of Blimp-1. Multiparametric flow cytometry was used to investigate TCDD-induced alterations in both activation marker and transcription factor expression following lipopolysaccharide (LPS) activation of purified B cells. TCDD significantly impaired LPS-activated expression of major histocompatibility complex class II, cluster of differentiation (CD)69, CD80, and CD86. Immunosuppressive concentrations of TCDD also suppressed LPS-activated Blimp-1 and phosphorylated c-Jun expression, whereas elevating BCL-6 expression. Because BCL-6 and c-Jun are directly and indirectly regulated by the kinases AKT, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK), it was hypothesized that TCDD alters toll-like receptor-activated kinase phosphorylation. TCDD at 0.03 and 0.3 nM significantly impaired phosphorylation of AKT, ERK, and JNK in CH12.LX B cells activated with LPS, CpG oligonucleotides, or resiquimod (R848). In primary B cells, R848-activated phosphorylation of AKT, ERK, and JNK was also impaired by TCDD at 30 nM. These results suggest that impairment of plasmacytic differentiation by TCDD involves altered transcription factor expression, in part, by suppressed kinase phosphorylation. PMID- 20348232 TI - 3-methylcholanthrene induces differential recruitment of aryl hydrocarbon receptor to human promoters. AB - The aryl hydrocarbon receptor (AHR) is a ligand-activated protein that mediates the toxic actions of polycyclic aromatic and halogenated compounds. Identifying genes directly regulated by AHR is important in understanding the pathways regulated by this receptor. Here we used the techniques of chromatin immunoprecipitation and DNA microarrays (ChIP-chip) to detect AHR-bound genomic regions after 3-methylcholanthrene (3MC) treatment of T-47D human breast cancer cells. We identified 241 AHR-3MC-bound regions, and transcription factor-binding site analysis revealed a strong overrepresentation of the AHR-responsive element. Conventional ChIP confirmed recruitment of AHR to 26 regions with target gene responses to 3MC varying from activation to inhibition to having no effect. A comparison of identified AHR-3MC-bound regions with AHR-2,3,7,8-tetrchlorodibenzo p-dioxin (TCDD)-bound regions from our previous study (Ahmed, S., Valen, E., Sandelin, A., and Matthews, J. (2009). Toxicol. Sci. 111, 254-266) revealed that 127 regions were common between the data sets. Time course ChIPs for six of the regions showed that 3MC induced gene-specific changes in histone H3 acetylation and methylation and induced differential oscillatory binding of AHR, with a periodicity between 1.5 and 2 h. Re-treatment of cells with 3MC failed to alter the oscillatory binding profiles of AHR or aryl hydrocarbon receptor nuclear translocator. Cells became responsive to 3MC but not TCDD after 24 h of exposure to 3MC, highlighting important differences in AHR responsiveness between the two ligands. Our results reveal a number of novel AHR-bound promoter regions and target genes that exhibit differential kinetic binding profiles and regulation by AHR. PMID- 20348233 TI - Impact of cultural and linguistic factors on symptom reporting by patients with cancer. AB - BACKGROUND: Patient reporting of the severity and impact of symptoms is an essential component of cancer symptom management and cancer treatment clinical trials. In multinational clinical trials, cultural and linguistic variations in patient-reported outcomes instruments could confound the interpretation of study results. METHODS: The severity and interference of multiple symptoms in 1433 cancer patients with mixed diagnoses and treatment status from the United States, China, Japan, Russia, and Korea were measured with psychometrically validated language versions of the M. D. Anderson Symptom Inventory (MDASI). Mixed-effect ordinal probit regression models were fitted to the pooled data to compare the magnitude of the effect of "country" (nation and linguistic factors) with between subjects effects on symptom reporting, adjusted for patient and clinical factors (age, sex, performance status, and chemotherapy status). RESULTS: For the pooled sample, fatigue, disturbed sleep, distress, pain, and lack of appetite were the most severe patient-reported MDASI symptoms. The magnitude of the variance of the country random effects was only one-fourth to one-half of the interpatient variation (sigma(2) = 0.23-0.46) for all symptoms, except nausea and vomiting. CONCLUSIONS: Cultural and linguistic variations in symptom reporting among the five language versions of the validated MDASI were limited. Ordinal probit modeling provided a simple mechanism for accounting for cultural and linguistic differences in patient populations. The equivalence among MDASI translations in this study suggests that symptom ratings collected from various cultural and language groups using the MDASI can be interpreted in a similar way in oncology practice, clinical trials, and clinical research. PMID- 20348234 TI - Enhanced tyrosine nitration of prostacyclin synthase is associated with increased inflammation in atherosclerotic carotid arteries from type 2 diabetic patients. AB - Prostacyclin synthase (PGIS) is tyrosine nitrated in diseased animals. Whether PGIS nitration occurs in human diabetic atherosclerotic arteries has not been reported. The present study was designed to determine PGIS nitration and its association with the inflammatory response in atherosclerotic carotid arteries from patients with or without type 2 diabetes, and carotid plaques were obtained from patients who underwent carotid endarterectomy. PGIS nitration, nitric oxide synthases, adhesion molecules, myeloperoxidase, osteopontin, and matrix metalloproteinase (MMP) were measured by using immunohistochemistry and Western blotting. In low stenosis areas, diabetes enhanced reactive nitrogen species production, as evidenced by increases in 3-nitrotyrosine and PGIS nitration. In parallel, diabetes dramatically increased inflammatory markers including intracellular adhesion molecule-1, vascular adhesion molecule-1, and osteopontin. In both diabetic and nondiabetic patients, MMP-2 and MMP-9 protein levels were significantly increased in the arteries with high stenosis as compared with those with low stenosis. Moreover, diabetes enhanced inducible nitric oxide synthase expression in the plaques from low stenosis areas and up-regulated myeloperoxidase expression in the plaques from both high and low stenosis areas. These data demonstrate that diabetes preferentially increases PGIS nitration that is associated with excessive vascular inflammation in atherosclerotic carotid arteries from patients with type 2 diabetes, suggesting a possible role of tyrosine nitration of PGIS in the development of atherosclerosis in patients with diabetes. PMID- 20348235 TI - Human intestinal ischemia-reperfusion-induced inflammation characterized: experiences from a new translational model. AB - Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-alpha, which was accompanied by IL 6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue. PMID- 20348236 TI - Suppressor of cytokine signaling-2 gene disruption promotes Apc(Min/+) tumorigenesis and activator protein-1 activation. AB - Epigenetic in vitro and in vivo studies suggest that suppressor of cytokine signaling-2 (SOCS2) may normally limit tumorigenesis in the intestine; however, this theory has not been directly tested. We hypothesized that SOCS2 deficiency promotes spontaneous intestinal tumorigenesis in Apc(Min/+) mice. Therefore, we quantified tumor number, size, and load in the small intestine and colon using SOCS2(+/+)/Apc(Min/+), SOCS2(+/-)/Apc(Min/+), and SOCS2(-/-)/Apc(Min/+) mice and assayed hematocrit as an indirect marker of disease severity. Biochemical and histological assays were used to assess mechanisms. Heterozygous and homozygous disruption of SOCS2 alleles promoted 166 and 441% increases in tumor load in the small intestine, respectively, accelerated development of colon tumors, and caused severe anemia. SOCS2 deletion promoted significant increases in intestinal insulin-like growth factor-I mRNA but did not affect plasma insulin-like growth factor-I. Western blots and immunohistochemical analysis demonstrated that tumor and nontumor intestinal tissue of SOCS2(-/-)/Apc(Min/+) mice had increased serine 727 phosphorylation of signal transducer and activator of transcription 3 compared with SOCS2(+/+)/Apc(Min/+) mice. Moreover, electromobility shift assays showed that SOCS2 deletion did not alter signal transducer and activator of transcription 3 DNA binding. However, tumors and small intestine from SOCS2(-/ )/Apc(Min/+) showed dramatic increases in activator protein-1 (AP-1) DNA binding, and SOCS2 overexpression in vitro reduced levels of AP-1. These studies indicate that SOCS2 deletion promotes the spontaneous development of intestinal tumors driven by mutations in the adenomatous polyposis coli/beta-catenin pathway and activates AP-1. Therefore, reduced expression or epigenetic silencing of SOCS2 may serve as a useful biomarker for colorectal cancer risk. PMID- 20348237 TI - Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression. AB - The plakophilins, members of the armadillo-repeat family, consist of three different proteins (PKP1-3) that are specifically recruited to desmosomal plaques in a highly cell type-specific manner. Using immunofluorescence, immunoelectron microscopy, and immunoblot, we found that all three plakophilins occurred in luminal and basal cells of the pseudostratified prostate epithelium. The analysis of 135 cases of prostatic adenocarcinomas grouped into tumors with low (Gleason score < or = 6), intermediate (Gleason score 7), and high Gleason score (8 < or = Gleason score < or = 10) showed that the expression of PKP1 was reduced or lost in adenocarcinomas with high Gleason scores. The expression of PKP2 was unchanged in all prostatic adenocarcinomas analyzed. In contrast, PKP3 expression was increased in carcinomas with high Gleason scores in comparison with carcinomas with low Gleason scores. In DU 145 cell lines with either overexpression or knockdown of PKP3, both imbalances resulted in fewer desmosomal cell contacts. In addition, overexpression of PKP3 in DU 145 cells led to an augmentation in proliferation rate. Our data imply that both loss of PKP1 and up-regulation of PKP3 expression are biologically important events in prostate cancer and are associated with a more aggressive phenotype. PMID- 20348238 TI - Immature osteoblast lineage cells increase osteoclastogenesis in osteogenesis imperfecta murine. AB - This study addressed the role of impairment of osteoblastic differentiation as a mechanism underlying pathophysiology of the osteogenesis imperfecta (OI). We hypothesized that combination of impaired osteogenic differentiation with increased bone resorption leads to diminished bone mass. By introducing visual markers of distinct stages of osteoblast differentiation, pOBCol3.6GFP (3.6GFP; preosteoblast) and pOBCol2.3GFP (2.3GFP; osteoblast/osteocytes), into the OIM model, we assessed osteoblast maturation and the mechanism of increased osteoclastogenesis. Cultures from oim/oim;2.3GFP mice showed a marked reduction of cells expressing GFP relative to +/+;2.3GFP littermates. No significant difference in expression of 3.6GFP between the +/+ and oim/oim mice was observed. Histological analysis of the oim/oim;3.6GFP mice showed an increased area of GFP positive cells lining the endocortical surface compared with +/+;3.6GFP mice. In contrast GFP expression was similar between oim/oim;2.3GFP and +/+;2.3GFP mice. These data indicate that the osteoblastic lineage is under continuous stimulation; however, only a proportion of cells attain the mature osteoblast stage. Indeed, immature osteoblasts exhibit a stronger potential to support osteoclast formation and differentiation. We detected a higher Rankl/Opg ratio and higher expression of TNF-alpha in sorted immature osteoblasts. In addition, increased osteoclast formation was observed when osteoclast progenitors were cocultured with oim/oim-derived osteoblasts compared with osteoblasts derived from +/+ mice. Taken together, our data indicate that osteoblast lineage maturation is a critical aspect underlying the pathophysiology of OI. PMID- 20348239 TI - Pathological features of heterologous immunity are regulated by the private specificities of the immune repertoire. AB - Heterologous immunity associated with cross-reactive T-cell responses is proposed to contribute to variations among individuals in the pathogenesis of human viral infections. In genetically identical mice with similar infection histories, marked variations in the magnitude and specificities of T-cell responses under conditions of heterologous immunity occur and have been linked to the private specificity of T-cell repertoires in individual immune mice. Variations in immunopathology in the form of panniculitis are observed in lymphocytic choriomeningitis virus-immune mice after vaccinia virus infection. By adoptively transferring splenocytes from individual lymphocytic choriomeningitis virus immune donors into paired recipients, we show here that, on vaccinia virus infection, similar levels of panniculitis were generated in recipients from a single donor, but the severity of panniculitis varied among recipients receiving cells from different donors. This indicates that virus-induced immunopathology under conditions of heterologous immunity is a function of the private specificity of the immune repertoire. PMID- 20348240 TI - The tetraspanin CD37 protects against glomerular IgA deposition and renal pathology. AB - The tetraspanin protein CD37 is a leukocyte-specific transmembrane protein that is highly expressed on B cells. CD37-deficient (CD37(-/-)) mice exhibit a 15-fold increased level of immunoglobulin A (IgA) in serum and elevated numbers of IgA+ plasma cells in lymphoid organs. Here, we report that CD37(-/-) mice spontaneously develop renal pathology with characteristics of human IgA nephropathy. In young naive CD37(-/-) mice, mild IgA deposition in glomeruli was observed. However, CD37(-/-) mice developed high titers of IgA immune complexes in serum during aging, which was associated with increased glomerular IgA deposition. Severe mesangial proliferation, fibrosis, and hyalinosis were apparent in aged CD37(-/-) mice, whereas albuminuria was mild. To further evaluate the role of CD37 in glomerular disease, we induced anti-glomerular basement membrane (GBM) nephritis in mice. CD37(-/-) mice developed higher IgA serum levels and glomerular deposits of anti-GBM IgA compared with wild-type mice. Importantly, glomerular macrophage and neutrophil influx was significantly higher in CD37(-/-) mice during both the heterologous and autologous phase of anti-GBM nephritis. Taken together, tetraspanin CD37 controls the formation of IgA-containing immune complexes and glomerular IgA deposition, which induces influx of inflammatory myeloid cells. Therefore, CD37 may protect against the development of IgA nephropathy. PMID- 20348241 TI - Critical roles of lysosomal acid lipase in myelopoiesis. AB - Lysosomal acid lipase (LAL) is a key enzyme that cleaves cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. Genetic ablation of the lal gene (lal(-/-)) in mice has resulted in a systemic increase of macrophages and neutrophils, causing severe inflammation and pathogenesis in multiple organs. We hypothesized that aberrant growth and differentiation of myeloid cells in lal(-/-) mice arises from dysregulated production of progenitor cells in the bone marrow. Indeed, lal(-/-) mice displayed increased numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells and granulocyte-macrophage precursors (GMP). Increased high proliferative potential colony-forming cells (HPP-CFC) were enumerated from cultured lal(-/-) bone marrow cells, as were significantly more CFU-GM, CFU-G, and CFU-M colonies. As a consequence, lal(-/-) mice developed significant myeloid infiltration, particularly with CD11b+/Gr-1+ myeloid-derived suppressive cells in multiple organs. Both decreased apoptosis and increased proliferation contribute to the systemic increase of myeloid cells in lal(-/-) myeloid cells. These lal(-/-) CD11b(+)/Gr-1(+) cells displayed suppressive activity on T cell proliferation and function in vitro. Bone marrow chimeras confirmed that the myeloproliferative disorder in lal(-/-) mice was primarily attributable to autonomous defects in myeloid progenitor cells, although the hematopoietic microenvironment in the lal(-/-) mice did not support hematopoiesis normally. These results provide evidence that LAL is an important regulator of myelopoiesis during hematopoietic development, differentiation, and homeostasis. PMID- 20348242 TI - Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. AB - In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-alpha than MDSCs isolated from the lung of MyD88 KO mice. In vitro, addition of tumor exosomes to bone marrow-derived CD11b(+)Gr-1(+) cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-alpha, interleukin-6, and the chemokine CCL2, than CD11b(+)Gr-1(+) cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis. PMID- 20348243 TI - Estrogen receptor alpha controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs. AB - Luminal-like breast tumor cells express estrogen receptor alpha (ERalpha), a member of the nuclear receptor family of ligand-activated transcription factors that controls their proliferation, survival, and functional status. To identify the molecular determinants of this hormone-responsive tumor phenotype, a comprehensive genome-wide analysis was performed in estrogen stimulated MCF-7 and ZR-75.1 cells by integrating time-course mRNA expression profiling with global mapping of genomic ERalpha binding sites by chromatin immunoprecipitation coupled to massively parallel sequencing, microRNA expression profiling, and in silico analysis of transcription units and receptor binding regions identified. All 1270 genes that were found to respond to 17beta-estradiol in both cell lines cluster in 33 highly concordant groups, each of which showed defined kinetics of RNA changes. This hormone-responsive gene set includes several direct targets of ERalpha and is organized in a gene regulation cascade, stemming from ligand activated receptor and reaching a large number of downstream targets via AP 2gamma, B-cell activating transcription factor, E2F1 and 2, E74-like factor 3, GTF2IRD1, hairy and enhancer of split homologue-1, MYB, SMAD3, RARalpha, and RXRalpha transcription factors. MicroRNAs are also integral components of this gene regulation network because miR-107, miR-424, miR-570, miR-618, and miR-760 are regulated by 17beta-estradiol along with other microRNAs that can target a significant number of transcripts belonging to one or more estrogen-responsive gene clusters. PMID- 20348244 TI - Dimethylarginine dimethylaminohydrolase overexpression ameliorates atherosclerosis in apolipoprotein E-deficient mice by lowering asymmetric dimethylarginine. AB - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is increasingly recognized as a novel biomarker in cardiovascular disease. To date, it remains unclear whether elevated ADMA levels are merely associated with cardiovascular risk or whether this molecule is of functional relevance in the pathogenesis of atherosclerotic vascular disease. To clarify this issue, we crossed dimethylarginine dimethylaminohydrolase (DDAH) transgenic mice that overexpress the human isoform 1 of the ADMA degrading enzyme DDAH into ApoE-deficient mice to generate ApoE(-/-)/hDDAH1(+/-) mice. In these mice, as well as ApoE(-/-) wild-type littermates, atherosclerosis within the aorta as well as vascular function of aortic ring preparations was assessed. We report here that overexpression of hDDAH1 reduces plaque formation in ApoE(-/-) mice by lowering ADMA. The extent of atherosclerosis closely correlated with plasma ADMA levels in male but not female mice fed either a standard rodent chow or an atherogenic diet. Functional analysis of aortic ring preparations revealed improved endothelial function in mice overexpressing hDDAH1. Our findings provide proof-of-principle that ADMA plays a causal role as a culprit molecule in atherosclerosis and support recent evidence indicating a functional relevance of DDAH enzymes in genetic mouse models. Together, these results demonstrate that pharmacological interventions targeting the ADMA/DDAH pathway may represent a novel approach in the prevention and management of cardiovascular diseases. PMID- 20348245 TI - The critical role of AKT2 in hepatic steatosis induced by PTEN loss. AB - Insulin signaling in the liver leads to accumulation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Deletion of the phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) reduces PIP3 levels and leads to fatty liver development. The purpose of this study was to investigate the mechanisms underlying lipogenesis that result from PIP3 accumulation using liver Pten deletion mice. To explore the role of AKT2, the major liver AKT isoform in steatosis induced by deletion of Pten, we created mice lacking both Pten and Akt2 in hepatocytes and compared the effect of deleting Akt2 and Pten in the double mutants to the Pten deletion mice alone. Hepatic lipid accumulation was significantly reduced in mice lacking both PTEN and AKT2, as compared with Pten mutant mice alone. This effect was due to the role of AKT2 in maintaining expression of genes involved in de novo lipogenesis. We showed that lipid accumulation in the double mutant hepatocytes was partially reversed by expression of constitutive active FOXO1, a transcription factor downstream of AKT not dependent on inhibition of atypical protein kinase C. In summary, this study delineated regulation of lipid metabolism by PI3K signaling pathway by showing that AKT mediates PIP3 accumulation (mimicked by PTEN loss) induced lipid deposition in the liver and provided an important molecular mechanism for insulin regulated hepatic lipogenesis. PMID- 20348246 TI - Tissue distribution and functional analysis of Sushi domain-containing protein 4. AB - Sushi domain-containing protein 4 (SUSD4) was a hypothetical cell surface protein whose tissue distribution and function were completely unknown. However, recent microarray-based studies have identified deletions of SUSD4 gene in patients with autism or Fryns syndrome, both of which are genetic diseases with severe abnormal neurological development and/or functions. In this article, we described the cloning, expression, refolding, tissue distribution, and functional analysis of this novel protein. Using polyclonal antibodies generated by immunizing chickens with the recombinant SUSD4, we found that SUSD4 is detectable in murine brains, eyes, spinal cords, and testis but not other tissues. In brains, SUSD4 is highly expressed in the white matter on oligodendrocytes/axons, and in eyes, it is exclusively expressed on the photoreceptor outer segments. In in vitro complement assays, SUSD4 augments the alternative but not the classical pathway of complement activation at the C3 convertase step. In in vivo studies, knocking down SUSD4 expression in zebrafish markedly increases ratios of mortality and developmental abnormality. These results provide the first insight into the important physiological roles of SUSD4 and could help to better understand the pathogenesis of autism and Fryns syndrome. PMID- 20348247 TI - The novel association of the chemokine CCL22 with abdominal aortic aneurysm. AB - The aim of this study was to examine aortic biopsies with a cytokine array to identify new cytokines associated with abdominal aortic aneurysm (AAA). We assessed the relative expression of 79 cytokines using antibody-based cytokine arrays in a total of 12 AAA and 12 control aortic biopsies. Based on these findings we validated the findings for one cytokine by examining a further 11 AAA and 11 atherothrombosis biopsies and serum from 1028 men, 315 of whom had an AAA. Three cytokines (interleukins 1B and 8, and Chemokine CC motif ligand 22 [CCL22]) were consistently up-regulated in AAA biopsies. Since CCL22 had not previously been associated with aortic dilatation, we confirmed the upregulation of this cytokine in further tissue biopsies and serum using enzyme-linked immunosorbent assay. Median serum concentrations of CCL22 were greater in men with AAA (0.69 ng/ml) than controls (0.56 ng/ml, P < 0.01). Serum CCL22 was independently associated with both small (OR 1.51, 95% CI 1.21-1.88) and large AAA (OR 1.33, 95% CI 1.08-1.62) after adjusting for other risk factors. The association between CCL22 and AAA was also confirmed using immunohistochemistry. The results presented in this study demonstrate a novel association between CCL22 and AAA as well as illustrate how a protein array can be used to identify novel markers of potential pathogenic and diagnostic significance for AAA. PMID- 20348248 TI - Genetic and epigenetic mechanisms down-regulate FGF receptor 2 to induce melanoma associated antigen A in breast cancer. AB - Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene encoding fibroblast growth factor receptor 2 (FGFR2) as a risk factor for breast cancer. We examined the relationship between these intron 2 SNPs and gene expression in breast carcinomas. Primary breast tissue showed a common occurrence of these SNPs accompanied by FGFR2 expression in normal ductal epithelium. Unexpectedly, we found that FGFR2 mRNA and protein levels were reduced in microdissected cancer cells when compared with paired normal breast epithelium. FGFR2 down-regulation was associated with DNA methylation and loss-of-heterozygosity. Where FGFR2-IIIb was expressed in tumor cells, it was accompanied by up-regulation of the RNA-binding proteins ESRP1/2, consistent with splicing of this isoform. Reduction in FGFR2 was associated with re-expression of its putative target melanoma-associated antigen (MAGE-A) in primary carcinoma cells. Conversely, forced expression or activation of FGFR2 IIIb resulted in MAGE-A silencing. These data provide the first evidence for FGFR2 down-regulation in breast carcinomas harboring intron 2 SNPs. Our findings underscore the significance of epigenetic and somatic changes that can potentially modify the effects of germline polymorphisms in determining FGFR2 gene expression. PMID- 20348249 TI - Structure and protein-protein interaction studies on Chlamydia trachomatis protein CT670 (YscO Homolog). AB - Comparative genomic studies have identified many proteins that are found only in various Chlamydiae species and exhibit no significant sequence similarity to any protein in organisms that do not belong to this group. The CT670 protein of Chlamydia trachomatis is one of the proteins whose genes are in one of the type III secretion gene clusters but whose cellular functions are not known. CT670 shares several characteristics with the YscO protein of Yersinia pestis, including the neighboring genes, size, charge, and secondary structure, but the structures and/or functions of these proteins remain to be determined. Although a BLAST search with CT670 did not identify YscO as a related protein, our analysis indicated that these two proteins exhibit significant sequence similarity. In this paper, we report that the CT670 crystal, solved at a resolution of 2 A, consists of a single coiled coil containing just two long helices. Gel filtration and analytical ultracentrifugation studies showed that in solution CT670 exists in both monomeric and dimeric forms and that the monomer predominates at lower protein concentrations. We examined the interaction of CT670 with many type III secretion system-related proteins (viz., CT091, CT665, CT666, CT667, CT668, CT669, CT671, CT672, and CT673) by performing bacterial two-hybrid assays. In these experiments, CT670 was found to interact only with the CT671 protein (YscP homolog), whose gene is immediately downstream of ct670. A specific interaction between CT670 and CT671 was also observed when affinity chromatography pull-down experiments were performed. These results suggest that CT670 and CT671 are putative homologs of the YcoO and YscP proteins, respectively, and that they likely form a chaperone-effector pair. PMID- 20348250 TI - Identification of Chlamydia trachomatis outer membrane complex proteins by differential proteomics. AB - The extracellular chlamydial infectious particle, or elementary body (EB), is enveloped by an intra- and intermolecular cysteine cross-linked protein shell called the chlamydial outer membrane complex (COMC). A few abundant proteins, including the major outer membrane protein and cysteine-rich proteins (OmcA and OmcB), constitute the overwhelming majority of COMC proteins. The identification of less-abundant COMC proteins has been complicated by limitations of proteomic methodologies and the contamination of COMC fractions with abundant EB proteins. Here, we used parallel liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses of Chlamydia trachomatis serovar L2 434/Bu EB, COMC, and Sarkosyl-soluble EB fractions to identify proteins enriched or depleted from COMC. All well-described COMC proteins were specifically enriched in the COMC fraction. In contrast, multiple COMC-associated proteins found in previous studies were strongly enriched in the Sarkosyl-soluble fraction, suggesting that these proteins are not COMC components or are not stably associated with COMC. Importantly, we also identified novel proteins enriched in COMC. The list of COMC proteins identified in this study has provided reliable information for further understanding chlamydial protein secretion systems and modeling COMC and EB structures. PMID- 20348251 TI - Growth phase-dependent activation of the DccRS regulon of Campylobacter jejuni. AB - Two-component systems are widespread prokaryotic signal transduction devices which allow the regulation of cellular functions in response to changing environmental conditions. The two-component system DccRS (Cj1223c-Cj1222c) of Campylobacter jejuni is important for the colonization of chickens. Here, we dissect the DccRS system in more detail and provide evidence that the sensor DccS selectively phosphorylates the cognate effector, DccR. Microarray expression profiling, real-time reverse transcription-PCR (RT-PCR), electrophoretic mobility shift assay, and primer extension analyses revealed that the DccRS regulon of strain 81116 consists of five promoter elements, all containing the consensus direct repeat sequence WTTCAC-N6-TTCACW covering the putative -35 promoter regions. One of these promoters is located in front of an operon encoding a putative macrolide efflux pump while the others are in front of genes coding for putative periplasmic or membrane proteins. The DccRS-regulated genes in C. jejuni strain 81116 are needed to enhance early in vivo growth of C. jejuni in 7-day-old chickens. The DccRS system is activated in the late stationary bacterial growth phase, probably by released metabolic products. Whole-genome mRNA profiling and real-time RT-PCR analysis under these conditions demonstrated that the system has no influence on the transcription of genes outside the DccRS regulon. PMID- 20348253 TI - Genome sequence of Pantoea ananatis LMG20103, the causative agent of Eucalyptus blight and dieback. AB - Pantoea ananatis is a Gram-negative plant pathogen that causes disease on a broad range of host plants, including pineapple, maize, rice, onion, melons, and Eucalyptus, and has been implicated in several cases of human disease. Here, we report the genome sequence of P. ananatis LMG20103 isolated from diseased Eucalyptus in South Africa. PMID- 20348252 TI - The sigma factor AlgU plays a key role in formation of robust biofilms by nonmucoid Pseudomonas aeruginosa. AB - The extracytoplasmic function sigma factor AlgU of Pseudomonas aeruginosa is responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. The algU mutant of P. aeruginosa PAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing the algU mutation with a plasmid-borne algU gene restored wild-type phenotypes. Compared with that in PAO1, expression of the psl operon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of the psl operon. Furthermore, expression of the lectin-encoding lecA and lecB genes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes, but AlgU is involved in the expression of the ppyR gene, whose product was reported to positively control psl expression. Expressing the ppyR gene in PAOU partially restored the formation of robust biofilms. PMID- 20348254 TI - In vitro and in vivo characterization of the Pseudomonas aeruginosa cyclic AMP (cAMP) phosphodiesterase CpdA, required for cAMP homeostasis and virulence factor regulation. AB - Cyclic AMP (cAMP) is an important second messenger signaling molecule that controls a wide variety of eukaryotic and prokaryotic responses to extracellular cues. For cAMP-dependent signaling pathways to be effective, the intracellular cAMP concentration is tightly controlled at the level of synthesis and degradation. In the opportunistic human pathogen Pseudomonas aeruginosa, cAMP is a key regulator of virulence gene expression. To better understand the role of cAMP homeostasis in this organism, we identified and characterized the enzyme CpdA, a putative cAMP phosphodiesterase. We demonstrate that CpdA possesses 3',5' cAMP phosphodiesterase activity in vitro and that it utilizes an iron-dependent catalytic mechanism. Deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of P. aeruginosa virulence traits. Further, we demonstrate that the cAMP-dependent transcription factor Vfr directly regulates cpdA expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression. PMID- 20348255 TI - Heterogeneous rpoS and rhlR mRNA levels and 16S rRNA/rDNA (rRNA gene) ratios within Pseudomonas aeruginosa biofilms, sampled by laser capture microdissection. AB - The local environmental conditions in biofilms are dependent on the impinging aqueous solution, chemical diffusion, and the metabolic activities of cells within the biofilms. Chemical gradients established in biofilms lead to physiological heterogeneities in bacterial gene expression. Previously, we used laser capture microdissection (LCM) and quantitative reverse transcription (RT) PCR to target defined biofilm subpopulations for gene expression studies. Here, we combined this approach with quantitative PCR of bacterial DNA to normalize the amount of gene expression per cell. By comparing the ratio of 16S rRNA to 16S rDNA (rRNA gene), we demonstrated that cells at the top of thick Pseudomonas aeruginosa biofilms have 16S rRNA/genome ratios similar to those of cells in a transition from the exponential phase to the stationary phase. Cells in the middle and bottom layers of these biofilms have ratios that are not significantly different from those of stationary-phase planktonic cultures. Since much of each biofilm appeared to be in a stationary-phase-like state, we analyzed the local amounts of the stationary-phase sigma factor rpoS gene and the quorum-sensing regulator rhlR gene per cell. Surprisingly, the amount of rpoS mRNA was largest at the top of the biofilms at the air-biofilm interface. Less than one rpoS mRNA transcript per cell was observed in the middle or base of the biofilms. The rhlR mRNA content was also greatest at the top of the biofilms, and there was little detectable rhlR expression at the middle or bottom of the biofilms. While the cell density was slightly greater at the bottom of the biofilms, expression of the quorum-sensing regulator occurred primarily at the top of the biofilms, where the cell metabolic activity was greatest, as indicated by local expression of the housekeeping gene acpP and by expression from a constitutive P(trc) promoter. The results indicate that in thick P. aeruginosa biofilms, cells in the 30 microm adjacent to the air-biofilm interface actively express genes associated with stationary phase, while cells in the interior portions do not express these genes and therefore are in a late-stationary-phase-like state and may be dormant. PMID- 20348256 TI - Longus, a type IV pilus of enterotoxigenic Escherichia coli, is involved in adherence to intestinal epithelial cells. AB - Enterotoxigenic Escherichia coli (ETEC) is the leading bacterial cause of diarrhea in the developing world, as well as the most common cause of traveler's diarrhea. The main hallmarks of this type of bacteria are the expression of one or more enterotoxins and fimbriae used for attachment to host intestinal cells. Longus is a pilus produced by ETEC. These bacteria grown in pleuropneumonia-like organism (PPLO) broth at 37 degrees C and in 5% CO(2) produced longus, showing that the assembly and expression of the pili depend on growth conditions and composition of the medium. To explore the role of longus in the adherence to epithelial cells, quantitative and qualitative analyses were done, and similar levels of adherence were observed, with values of 111.44 x 10(4) CFU/ml in HT-29, 101.33 x 10(4) CFU/ml in Caco-2, and 107.11 x 10(4) CFU/ml in T84 cells. In addition, the E9034A Delta lngA strain showed a significant reduction in longus adherence of 32% in HT-29, 22.28% in Caco-2, and 21.68% in T84 cells compared to the wild-type strain. In experiments performed with nonintestinal cells (HeLa and HEp-2 cells), significant differences were not observed in adherence between E9034A and derivative strains. Interestingly, the E9034A and E9034A Delta lngA(pLngA) strains were 30 to 35% more adherent in intestinal cells than in nonintestinal cells. Twitching motility experiments were performed, showing that ETEC strains E9034A and E9034A Delta lngA(pLngA) had the capacity to form spreading zones while ETEC E9034A Delta lngA does not. In addition, our data suggest that longus from ETEC participates in the colonization of human colonic cells. PMID- 20348257 TI - Agrobacterium tumefaciens type IV secretion protein VirB3 is an inner membrane protein and requires VirB4, VirB7, and VirB8 for stabilization. AB - Agrobacterium tumefaciens VirB proteins assemble a type IV secretion apparatus and a T-pilus for secretion of DNA and proteins into plant cells. The pilin-like protein VirB3, a membrane protein of unknown topology, is required for the assembly of the T-pilus and for T-DNA secretion. Using PhoA and green fluorescent protein (GFP) as periplasmic and cytoplasmic reporters, respectively, we demonstrate that VirB3 contains two membrane-spanning domains and that both the N and C termini of the protein reside in the cytoplasm. Fusion proteins with GFP at the N or C terminus of VirB3 were fluorescent and, like VirB3, localized to a cell pole. Biochemical fractionation studies demonstrated that VirB3 proteins encoded by three Ti plasmids, the octopine Ti plasmid pTiA6NC, the supervirulent plasmid pTiBo542, and the nopaline Ti plasmid pTiC58, are inner membrane proteins and that VirB4 has no effect on membrane localization of pTiA6NC-encoded VirB3 (pTiA6NC VirB3). The pTiA6NC and pTiBo542 VirB2 pilins, like VirB3, localized to the inner membrane. The pTiC58 VirB4 protein was earlier found to be essential for stabilization of VirB3. Stabilization of pTiA6NC VirB3 requires not only VirB4 but also two additional VirB proteins, VirB7 and VirB8. A binary interaction between VirB3 and VirB4/VirB7/VirB8 is not sufficient for VirB3 stabilization. We hypothesize that bacteria use selective proteolysis as a mechanism to prevent assembly of unproductive precursor complexes under conditions that do not favor assembly of large macromolecular structures. PMID- 20348258 TI - Genome sequence of hybrid Vibrio cholerae O1 MJ-1236, B-33, and CIRS101 and comparative genomics with V. cholerae. AB - The genomes of Vibrio cholerae O1 Matlab variant MJ-1236, Mozambique O1 El Tor variant B33, and altered O1 El Tor CIRS101 were sequenced. All three strains were found to belong to the phylocore group 1 clade of V. cholerae, which includes the 7th-pandemic O1 El Tor and serogroup O139 isolates, despite displaying certain characteristics of the classical biotype. All three strains were found to harbor a hybrid variant of CTXPhi and an integrative conjugative element (ICE), leading to their establishment as successful clinical clones and the displacement of prototypical O1 El Tor. The absence of strain- and group-specific genomic islands, some of which appear to be prophages and phage-like elements, seems to be the most likely factor in the recent establishment of dominance of V. cholerae CIRS101 over the other two hybrid strains. PMID- 20348259 TI - Biochemical characterization of a novel indole prenyltransferase from Streptomyces sp. SN-593. AB - Genome sequencing of Streptomyces species has highlighted numerous potential genes of secondary metabolite biosynthesis. The mining of cryptic genes is important for exploring chemical diversity. Here we report the metabolite-guided genome mining and functional characterization of a cryptic gene by biochemical studies. Based on systematic purification of metabolites from Streptomyces sp. SN 593, we isolated a novel compound, 6-dimethylallylindole (DMAI)-3-carbaldehyde. Although many 6-DMAI compounds have been isolated from a variety of organisms, an enzyme catalyzing the transfer of a dimethylallyl group to the C-6 indole ring has not been reported so far. A homology search using known prenyltransferase sequences against the draft sequence of the Streptomyces sp. SN-593 genome revealed the iptA gene. The IptA protein showed 27% amino acid identity to cyanobacterial LtxC, which catalyzes the transfer of a geranyl group to (-) indolactam V. A BLAST search against IptA revealed much-more-similar homologs at the amino acid level than LtxC, namely, SAML0654 (60%) from Streptomyces ambofaciens ATCC 23877 and SCO7467 (58%) from S. coelicolor A3(2). Phylogenetic analysis showed that IptA was distinct from bacterial aromatic prenyltransferases and fungal indole prenyltransferases. Detailed kinetic analyses of IptA showed the highest catalytic efficiency (6.13 min(-1) microM(-1)) for L-Trp in the presence of dimethylallyl pyrophosphate (DMAPP), suggesting that the enzyme is a 6-dimethylallyl-L-Trp synthase (6-DMATS). Substrate specificity analyses of IptA revealed promiscuity for indole derivatives, and its reaction products were identified as novel 6-DMAI compounds. Moreover, DeltaiptA mutants abolished the production of 6-DMAI-3-carbaldehyde as well as 6-dimethylallyl-L-Trp, suggesting that the iptA gene is involved in the production of 6-DMAI-3-carbaldehyde. PMID- 20348260 TI - Negative regulation of expression of the nitrate assimilation nirA operon in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. AB - In the filamentous, heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120, expression of the nitrate assimilation nirA operon takes place in the absence of ammonium and the presence of nitrate or nitrite. Several positive action proteins that are required for expression of the nirA operon have been identified. Whereas NtcA and NtcB exert their action by direct binding to the nirA operon promoter, CnaT acts by an as yet unknown mechanism. In the genome of this cyanobacterium, open reading frame (ORF) all0605 (the nirB gene) is found between the nirA (encoding nitrite reductase) and ntcB genes. A nirB mutant was able to grow at the expense of nitrate as a nitrogen source and showed abnormally high levels of nirA operon mRNA both in the presence and in the absence of nitrate. This mutant showed increased nitrate reductase activity but decreased nitrite reductase activity, an imbalance that resulted in excretion of nitrite, which accumulated in the extracellular medium, when the nirB mutant was grown in the presence of nitrate. A nirA in-frame deletion mutant also showed a phenotype of increased expression of the nirA operon in the absence of ammonium, independent of the presence of nitrate in the medium. Both NirB and NirA are therefore needed to keep low levels of expression of the nirA operon in the absence of an inducer. Because NirB is also needed to attain high levels of nitrite reductase activity, NirA appears to be a negative element in the nitrate regulation of expression of the nirA operon in Anabaena sp. strain PCC 7120. PMID- 20348261 TI - Two distantly homologous DnaG primases from Thermoanaerobacter tengcongensis exhibit distinct initiation specificities and priming activities. AB - Primase, encoded by dnaG in bacteria, is a specialized DNA-dependent RNA polymerase that synthesizes RNA primers de novo for elongation by DNA polymerase. Genome sequence analysis has revealed two distantly related dnaG genes, TtdnaG and TtdnaG(2), in the thermophilic bacterium Thermoanaerobacter tengcongensis. Both TtDnaG (600 amino acids) and TtDnaG2 (358 amino acids) exhibit primase activities in vitro at a wide range of temperatures. Interestingly, the template recognition specificities of these two primases are quite distinctive. When trinucleotide-specific templates were tested, TtDnaG initiated RNA primer synthesis efficiently only on templates containing the trinucleotide 5'-CCC-3', not on the other 63 possible trinucleotides. When the 5'-CCC-3' sequence was flanked by additional cytosines or guanines, the initiation efficiency of TtDnaG increased remarkably. Significantly, TtDnaG could specifically and efficiently initiate RNA primer synthesis on a limited set of tetranucleotides composed entirely of cytosines and guanines, indicating that TtDnaG initiated RNA primer synthesis more preferably on GC-containing tetranucleotides. In contrast, it seemed that TtDnaG2 had no specific initiation nucleotides, as it could efficiently initiate RNA primer synthesis on all templates tested. The DNA binding affinity of TtDnaG2 was usually 10-fold higher than that of TtDnaG, which might correlate with its high activity but low template specificity. These distinct priming activities and specificities of TtDnaG and TtDnaG2 might shed new light on the diversity in the structure and function of the primases. PMID- 20348262 TI - Complete genome sequence of the thermophilic, obligately chemolithoautotrophic hydrogen-oxidizing bacterium Hydrogenobacter thermophilus TK-6. AB - Hydrogenobacter thermophilus is a thermophilic, obligately chemolithoautotrophic and aerobic hydrogen-oxidizing bacterium. It is unique in its ability to fix carbon dioxide via the reductive tricarboxylic acid cycle under aerobic conditions. It utilizes molecular hydrogen, elemental sulfur, or thiosulfate as the sole energy source. Here, we report the complete genome sequence of H. thermophilus TK-6. PMID- 20348263 TI - Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain. AB - In syphilis research, the Nichols strain of Treponema pallidum, isolated in 1912, has been the most widely studied. Recently, important differences among T. pallidum strains emerged; therefore, we sequenced and annotated the Chicago strain genome to facilitate and encourage the use of this strain in studying the pathogenesis of syphilis. PMID- 20348264 TI - Complete genome sequence of the probiotic Lactobacillus casei strain BL23. AB - The entire genome of Lactobacillus casei BL23, a strain with probiotic properties, has been sequenced. The genomes of BL23 and the industrially used probiotic strain Shirota YIT 9029 (Yakult) seem to be very similar. PMID- 20348265 TI - Genome sequence of naturally competent Aggregatibacter actinomycetemcomitans serotype a strain D7S-1. AB - The major clonal lineages of the Gram-negative periodontal pathogen Aggregatibacter actinomycetemcomitans include serotype a, b, and c strains. Here, we report the draft genome sequence of a naturally competent serotype a strain, D7S-1, isolated from a patient with aggressive periodontitis. PMID- 20348266 TI - Complete genome sequence of Lactococcus lactis subsp. lactis KF147, a plant associated lactic acid bacterium. AB - Lactococcus lactis is a lactic acid bacterium used in the production of many fermented dairy products. We report the complete genome sequence of L. lactis subsp. lactis KF147, a nondairy strain isolated from mung bean sprouts. The circular chromosome of 2,598,144 bp, the largest among the sequenced lactococcal strains, encodes many properties related to adaptation to the plant environment. PMID- 20348267 TI - Expanded role for the nitrogen assimilation control protein in the response of Klebsiella pneumoniae to nitrogen stress. AB - Klebsiella pneumoniae is able to utilize many nitrogen sources, and the utilization of some of these nitrogen sources is dependent on the nitrogen assimilation control (NAC) protein. Seven NAC-regulated promoters have been characterized in K. pneumoniae, and nine NAC-regulated promoters have been found by microarray analysis in Escherichia coli. So far, all characterized NAC regulated promoters have been directly related to nitrogen metabolism. We have used a genome-wide analysis of NAC binding under nitrogen limitation to identify the regions of the chromosome associated with NAC in K. pneumoniae. We found NAC associated with 99 unique regions of the chromosome under nitrogen limitation. In vitro, 84 of the 99 regions associate strongly enough with purified NAC to produce a shifted band by electrophoretic mobility shift assay. Primer extension analysis of the mRNA from genes associated with 17 of the fragments demonstrated that at least one gene associated with each fragment was NAC regulated under nitrogen limitation. The large size of the NAC regulon in K. pneumoniae indicates that NAC plays a larger role in the nitrogen stress response than it does in E. coli. Although a majority of the genes with identifiable functions that associated with NAC under nitrogen limitation are involved in nitrogen metabolism, smaller subsets are associated with carbon and energy acquisition (18 genes), and growth rate control (10 genes). This suggests an expanded role for NAC regulation during the nitrogen stress response, where NAC not only regulates genes involved in nitrogen metabolism but also regulates genes involved in balancing carbon and nitrogen pools and growth rate. PMID- 20348268 TI - Lactic acid levels in patients with chronic obstructive pulmonary disease accomplishing unsupported arm exercises. AB - Patients with chronic obstructive pulmonary disease (COPD) may suffer dyspnea when performing unsupported arm exercises (UAE). However, some factors related to the tolerance of the upper limbs during these exercises are not well understood. Our investigation was to determine if an unsupported arm exercise test in patients with COPD accomplishing diagonal movements increases lactic acid levels; also, we assessed the metabolic, ventilatory and cardiovascular responses obtained from the unsupported arm exercise test. The study used results of maximal symptom limited tests with unsupported arms and legs performed on 16 patients with COPD. In order to do the test, some metabolic, respiratory and cardiovascular parameters such as oxygen uptake (VO(2)), carbon dioxide production (VCO(2)), respiratory rate (RR), pulmonary ventilation (VE), heart rate (HR) and blood pressure (BP) were measured during the exercise tests. Furthermore, blood lactate concentration was measured during the arm test. We detected a significant increase in the mean blood lactate concentration, VO(2), VCO(2), VE and RR from the resting to the peak phase of the UAE test. The mean values of VO(2), VCO(2) and VE obtained at the peak of the UAE test corresponded to 52.5%, 50.0% and 61.2%, respectively, of the maximal values obtained at the peak of the leg exercise test. In comparison, the mean heart rate and systolic arterial blood pressure were significantly lower at the peak of the UAE test than at the peak leg exercise test and corresponded to 76.2% and 83.0%, respectively. Unsupported incremental arm exercises in patients with COPD increases blood lactic acid levels. PMID- 20348269 TI - Long-term outcome of division of the C8 nerve root for spasticity of the hand in cerebral palsy. AB - Division of the C8 nerve root results in short-term relief of spasticity in the hands of cerebral palsy patients. In the present study, we assessed the long-term outcome of C8 nerve root division. Between March 1997 and January 2002, this procedure was done in 13 patients. All received consistent postoperative functional rehabilitation training. The hands were assessed before operation and at follow-up using the Lazareff grading system. The average follow-up time was 8.6 years. Two hands showed excellent improvement, three limbs showed good improvement and eight hands showed no improvement. No long-term complications occurred in any patient. These results indicate that the long-term outcome of C8 nerve root rhizotomy for the treatment of hand spasticity in CP is generally poor. PMID- 20348270 TI - Cost variations in ambulatory and home-based palliative care. AB - Restructuring health care in Canada has emphasized the provision of ambulatory and home-based palliative care. Acquiring economic evidence is critical given this trend and its tremendous demands on family caregivers. The purposes of this study were: 1) to comprehensively assess the societal costs of home-based palliative care; and 2) to examine the socio-demographic and clinical factors that account for variations in costs over the course of the palliative trajectory. One hundred and thirty-six family caregivers were interviewed every two weeks from time of palliative referral until death. Information regarding appointments, travel and out-of-pocket expenses, time devoted to caregiving, as well as demographic and clinical characteristics were measured. The mean monthly cost of care per patient was $24,549 (2008 CDN$). Family caregivers' time costs comprised most costs (70%). Multivariable linear regression indicated that costs were greater for patients who: had lower physical functioning (p < 0.001); lived with someone (p = 0.007); and when the patients approached death (p = 0.021). Information highlighting the variation in costs across individuals may aid policy makers and mangers in deciding how to allocate resources. Greater clarity regarding costs over the course of the palliative trajectory may improve access to care. PMID- 20348271 TI - The impact of opioids, anticholinergic medications and disease progression on the prescription of laxatives in hospitalized palliative care patients: a retrospective analysis. AB - Definitive risk factors for constipation in palliative care remain poorly defined. A retrospective analysis of 211 admissions to a palliative care unit was undertaken, with the main aim being to identify some factors, which influence laxative prescription. On univariate analysis, significant unadjusted associations were found between two or more prescribed laxatives and a diagnosis of malignancy, morphine equivalent dose, type of illness phase and the subsequent phase type, length of phase, anticholinergic load imposed by medications, symptom severity and functional status. Multiple ordinal logistic regressions revealed the prescription of one laxative to be significantly associated with oral morphine-equivalent dose, total anticholinergic load (odds ratio [OR] 1.4, 95% CI = 1.0-2.0), disease progression to terminal phase and death (OR 0.1, 95% CI = 0.0 0.3), and length of phase (OR 1.1, 95% CI = 1.0-1.2). Similar results were obtained for the prescription of two or more laxatives. Two additional measures of function, toileting (OR 3.6, 95% CI = 1.6-8.2) and transfer (OR 0.4 95% CI = 0.2-0.9), also became significant. Total anticholinergic load was significantly associated with the prescription of a single laxative (OR 1.4, 95% CI = 1.0-2.0) and two or more laxatives (OR 1.8, 95% CI = 1.3-2.5) for each unit increase in anticholinergic load. Opioids and in particular opioids prescribed at higher doses, the total anticholinergic load associated with prescribed medications, the degree of impaired physical function of a person, their length of stay in a palliative care unit and their proximity to death were all strongly related to the prescription of laxatives. PMID- 20348272 TI - Current and planned palliative care service provision for chronic obstructive pulmonary disease patients in 239 UK hospital units: comparison with the gold standards framework. AB - Patients with chronic obstructive pulmonary disease report a symptom burden similar in magnitude to terminal cancer patients yet service provision and access has been reported as poor. In the absence of a specific national chronic obstructive pulmonary disease service framework the gold standards framework might support service developments. We surveyed 239 UK acute hospital units admitting chronic obstructive pulmonary disease patients, comprising 98% of all acute trusts, about their current and planned provision for palliative care services. Only 49% of units had a formal referral pathway for palliative care and only 13% had a policy of initiating end-of-life discussions with appropriate patients. Whilst 66% of units had plans to develop palliative care services, when mapped against the gold standards framework few were directly relevant and only three of the seven key standards were covered to any significant degree. We conclude that service provision remains poor and access is hindered by a lack of proactive initiation of discussion. Planned developments in chronic obstructive pulmonary disease palliative care services also lack a strategic framework that risks holistic design. PMID- 20348273 TI - Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? AB - CONTEXT: Peritoneal carcinomatosis (PC) is a rare site of distant metastases in patients with adrenocortical cancer (ACC). One preliminary study suggests an increased risk of PC after laparoscopic adrenalectomy (LA) for ACC. OBJECTIVE: The objective of the study was to search for risk factors of PC including surgical approach. DESIGN: This was a retrospective cohort study conducted in an institutional practice. PATIENTS: Sixty-four consecutive patients with ACC seen at our institution between 2003 and 2009 were included. Mean tumor size was 132 mm. Patients had stage I disease in 2 cases, stage II disease in 32 cases, stage III disease in 7 cases, stage IV disease in 21 cases, and unknown stage disease in 2 cases. Surgery was open in 58 cases and laparoscopic in 6 cases. MAIN OUTCOME: The main outcome was the risk factors of PC. RESULTS: PC occurred in 18 (28%) patients. It was present at initial diagnosis in three cases and occurred during follow-up in 15 cases. The only risk factor of PC occurring during follow up was the surgical approach with a 4-year rate of PC of 67% (95% confidence interval (CI), 30-90%) for LA and 27% (95% CI, 15-44%) for open adrenalectomy (P=0.016). Neither tumor size, stage, functional status, completeness of surgery, nor plasma level of op'DDD was associated with the occurrence of PC. CONCLUSION: We found an increased risk of PC after LA for ACC. Whether this is related to an inappropriate surgical approach or to insufficient experience in ACC surgery should be clarified by a prospective program. PMID- 20348274 TI - Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety. AB - BACKGROUND: Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits. METHODS: A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used. RESULTS: Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively. CONCLUSIONS: ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity. PMID- 20348275 TI - Motivations for sexual risk behavior across commercial and casual partners among male urban drug users: contextual features and clinical correlates. AB - The current study aimed to develop a measure for assessing the various motivations for sexual risk behavior (SRB) across commercial (involving the exchange of sex for money or drugs) and casual (nonregular) partners in a sample of inner-city, primarily African American drug users, and to examine the relationship of these motivations with a history of childhood trauma, as well as current symptoms of depression, posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). Exploratory factor analysis indicated a 5 factor solution for commercial partner type, and a 4-factor solution for casual partner type, including the motivations of sexual sensation-seeking, intimacy seeking, reassurance-seeking, emotional avoidance, and emotional expressivity. Emotional avoidance and emotional expressivity were strongly related to childhood trauma and PTSD and BPD symptoms. These results provide initial results for mechanisms underlying the relationship between SRB and a history of trauma and psychopathology. PMID- 20348276 TI - Affects of ionizing radiation on T-cell population lymphocyte: a risk factor of irritable bowel syndrome. AB - Irritable bowel syndrome is observed mostly in Ukrainian children and may be related to adverse health effects as a result of the Chernobyl disaster. The aim of this study was to determine status of T-cell population lymphocytes in children with clinical symptom of irritable bowel syndrome. The test population consisted of 95 participants: 75 rural patients aged 4 to 18 who lived in a contaminated area exposed to natural environmental radiation with clinical symptom of irritable bowel syndrome (categorized in three groups) and 20 healthy urban participants from Kiev aged 5 to 15 as control group. Internal radiation activity has been measured by gamma-ray spectrometry. Peripheral blood leukocytes were analyzed for T-lymphocytes subset such as T-lymphocytes (CD3(+)), T-helper (CD4(+)) and T-cytotoxic (CD8(+)) and then CD4/CD8 ratio was calculated. Percentage of CD3(+) and CD4(+) in all study groups decreased significantly in comparison to control group (p < 0.001). Percentage of CD8(+) increased significantly in all study groups in comparison to control group (p < 0.05). The CD4/CD8 ratio decreased significantly all study groups in comparison to control group (p < 0.001). Cellular immune status of study groups that are residing in a contaminated area has changed. Our data have demonstrated that this change may be related to a higher incidence of children with irritable bowel syndrome. PMID- 20348277 TI - Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced angiopoietin-2 and VEGF. AB - Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls. ELISA determination indicated little ANG-1 change during pregnancy and no effect of LH, whereas Tie-2 declined similarly between 9 and 37 wk in LH and controls. By contrast, ANG-2 markedly increased in LH from 24 wk, whereas it remained stable in controls. Because VEGF increased also, this was interpreted as an attempt to overcome vascular underdevelopment. Hypothesizing that its inefficiency might be due to impaired downstream mechanism, endothelial nitric oxide synthase (eNOS) was determined by semiquantitative Western blot and found to be reduced by approximately 75%, mostly in the instance of CDH. In conclusion, angiogenesis remains defective in hypoplastic lungs despite reactive enhancement of VEGF and ANG-2 production, which could be due, at least in part, to insufficient eNOS expression. PMID- 20348278 TI - Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation. AB - Inflammation is associated with various pulmonary diseases and contributes to the pathogenesis of acute lung injury. We previously identified a proinflammatory signaling pathway triggered by G protein-coupled receptors (GPCRs) in which stimulation of G(q)-coupled GPCRs results in activation of the transcription factor NF-kappaB. Because damage to the lung causes the release of multiple mediators acting through G(q)-coupled GPCRs, this signaling pathway is likely to contribute to inflammatory processes in the injured lung. In an effort to identify novel inhibitors of lung inflammation, the National Institutes of Health Clinical Collection, a library of 446 compounds, was screened for inhibitory activity toward production of IL-8 induced by stimulation of the G(q)-coupled tachykinin 1 receptor with substance P in A549 cells. Twenty-eight compounds that significantly inhibited substance P-induced IL-8 production were identified. The most potent inhibitor was triptolide, a diterpenoid compound from Tripterygium wilfordii Hook F, a vine used in traditional Chinese medicine for the treatment of autoimmune diseases. Triptolide inhibited IL-8 production induced by substance P with an IC(50) of 2.3 x 10(-8) M and inhibited NF-kappaB activation in response to an agonist of the protease-activated receptor 2 with an IC(50) of 1.4 x 10(-8) M. Anti-inflammatory effects of triptolide were assessed in vivo using a chlorine gas lung injury model in mice. Triptolide inhibited neutrophilic inflammation and the production of KC (Cxcl1) in the lungs of chlorine-exposed mice. The results demonstrate that triptolide exhibits anti-inflammatory activity in cultured lung cells and in an in vivo model of acute lung injury. PMID- 20348279 TI - Regulation of heme oxygenase-1 gene by peptidoglycan involves the interaction of Elk-1 and C/EBPalpha to increase expression. AB - Heme oxygenase (HO)-1 is a cytoprotective enzyme with anti-inflammatory properties. HO-1 is induced during a systemic inflammatory response, and expression of HO-1 is beneficial during sepsis of a Gram-positive source. Systemic infection from Gram-positive organisms has emerged as an important cause of sepsis, with Staphylococcus aureus as a common etiology. An important mediator of Gram-positive infections is peptidoglycan (PGN), a cell wall component of these organisms. Here, we demonstrate that HO-1 played an important, protective role in vivo, as mice deficient in HO-1 were very sensitive to the lethal effects of PGN derived from S. aureus. PGN induced HO-1 protein and mRNA levels, and this regulation occurred at the level of gene transcription. The PGN-responsive region of the HO-1 promoter (from -117 to -66 bp) contains a functional EBS, and Ets proteins are known to be involved in the regulation of inflammatory responses. We showed previously that Ets factors (activators Ets-2 and Ets-1 and repressor Elk 3) regulate HO-1 expression by Gram-negative endotoxin. However, during exposure to a Gram-positive stimulus in the present study, Elk-1 was a potent activator of HO-1 in conjunction with PGN. The ability of Elk-1 to induce HO-1 promoter activity was independent of direct DNA binding, but rather occurred by interacting with the CCAAT/enhancer-binding protein-alpha (C/EBPalpha), which binds to DNA. Moreover, silencing of C/EBPalpha in macrophages prevented induction of HO-1 promoter activity by either Elk-1 or PGN. These data provide further insight into the regulation and function of HO-1 by a mediator of Gram positive bacteria. PMID- 20348280 TI - Mechanotransduction by GEF-H1 as a novel mechanism of ventilator-induced vascular endothelial permeability. AB - Pathological lung overdistention associated with mechanical ventilation at high tidal volumes (ventilator-induced lung injury; VILI) compromises endothelial cell (EC) barrier leading to development of pulmonary edema and increased morbidity and mortality. We have previously shown involvement of microtubule (MT) associated Rho-specific guanine nucleotide exchange factor GEF-H1 in the agonist induced regulation of EC permeability. Using an in vitro model of human pulmonary EC exposed to VILI-relevant magnitude of cyclic stretch (18% CS) we tested a hypothesis that CS-induced alterations in MT dynamics contribute to the activation of Rho-dependent signaling via GEF-H1 and mediate early EC response to pathological mechanical stretch. Acute CS (30 min) induced disassembly of MT network, cell reorientation, and activation of Rho pathway, which was prevented by MT stabilizer taxol. siRNA-based GEF-H1 knockdown suppressed CS-induced disassembly of MT network, abolished Rho signaling, and attenuated CS-induced stress fiber formation and EC realignment compared with nonspecific RNA controls. Depletion of GEF-H1 in the murine two-hit model of VILI attenuated vascular leak induced by lung ventilation at high tidal volume and thrombin-derived peptide TRAP6. These data show for the first time the critical involvement of microtubules and microtubule-associated GEF-H1 in lung vascular endothelial barrier dysfunction induced by pathological mechanical strain. PMID- 20348281 TI - Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis. AB - Pulmonary fibroblasts regulate extracellular matrix production and degradation and are critical in maintenance of lung structure, function, and repair, but they also play a central role in lung fibrosis. cAMP-elevating agents inhibit cytokine and growth factor-stimulated myofibroblast differentiation and collagen synthesis in pulmonary fibroblasts. In the present study, we overexpressed adenylyl cyclase 6 (AC6) in pulmonary fibroblasts and measured cAMP production and collagen synthesis. AC6 overexpression enhanced cAMP production and the inhibition of collagen synthesis mediated by isoproterenol and beraprost, but not the responses to butaprost or PGE(2). To examine if increased AC6 expression would impact the development of fibrosis in an animal model, we generated transgenic mice that overexpress AC6 under a fibroblast-specific promoter, FTS1. Lung fibrosis was induced in FTS1-AC6(+/-) mice and littermate controls by intratracheal instillation of saline or bleomycin. Wild-type mice treated with bleomycin showed extensive peribronchial and interstitial fibrosis and collagen deposition. By contrast, FTS1-AC6(+/-) mice displayed decreased fibrotic development, lymphocyte infiltration (as determined by pathological scoring), and lung collagen content. Thus, AC6 overexpression inhibits fibrogenesis in the lung by reducing pulmonary fibroblast-mediated collagen synthesis and myofibroblast differentiation. Because AC6 overexpression does not lead to enhanced basal or PGE(2)-stimulated levels of cAMP, we conclude that endogenous catecholamines or prostacyclin is produced during bleomycin-induced lung fibrosis and that these signals have antifibrotic potential. PMID- 20348282 TI - Footwear traction and lower extremity joint loading. AB - BACKGROUND: Traction is influenced by the sole architecture and playing surface, with increases in traction potentially leading to injury. The mechanism as to how or why increased traction could lead to injury remains unknown. PURPOSE: This study was undertaken to determine how shoes of different sole designs and traction influence knee and ankle joint moments. STUDY DESIGN: Controlled laboratory study. METHODS: Traction testing was performed on 2 shoes of varying sole designs (tread vs smooth) using a robotic testing machine. All testing was conducted on a 60-cm x 90-cm piece of sample track surface. Kinematic and kinetic data were then collected on 13 recreational athletes performing running V-cuts in the 2 different shoe conditions. Five trials per condition were collected with reflective markers placed on the right shank and shoe of each participant. Kinematic and kinetic data were collected using an 8-high-speed camera system and force plate. RESULTS: The coefficient of translational traction and the peak moment of rotation were both significantly higher in the tread shoe compared with the smooth shoe (1.00 vs 0.87 and 23.87 N.m vs 16.12 N.m, respectively). The high traction shoe had significantly higher peak ankle external rotation moments (89.58 N.m vs 80.17 N.m), peak knee external rotation moments (36.23 N.m vs 32.02 N.m), peak knee adduction moments (224.0 N.m vs 186.8 N.m), and knee adduction angular impulse (2.10 Nms vs 1.83 Nms) compared with the low-traction shoe. CONCLUSION: Increased shoe traction significantly increased ankle and knee joint moments during a V-cut. Despite the significant difference in traction, no difference in performance was observed. These changes could have an effect on ankle and knee joint injury. CLINICAL RELEVANCE: Shoes with decreased traction could be used in sports to reduce the joint moments in the knee and ankle and potentially reduce injury without a loss in performance. PMID- 20348283 TI - Oblique femoral tunnel placement can increase risks of short femoral tunnel and cross-pin protrusion in anterior cruciate ligament reconstruction. AB - BACKGROUND: A more horizontal femoral tunnel has been emphasized for contemporary anterior cruciate ligament (ACL) reconstruction. However, lowering the femoral tunnel may result in a shorter tunnel. In addition, a more horizontally placed femoral tunnel may have inadequate bone stock at the posterior portion of the tunnel, which can lead to protrusion of the cross-pin (Rigidfix) system for femoral fixation. HYPOTHESIS: A more horizontal femoral tunnel position, particularly via the anteromedial (AM) portal technique, will reduce femoral tunnel length, and a more horizontal femoral tunnel position and anterior-to posterior pin insertion will increase the risk of Rigidfix pin protrusion. STUDY DESIGN: Controlled laboratory study. METHODS: In 10 cadaveric knees, we measured maximum lengths of the femoral tunnels at the positions of 11:30, 10:30, and 9:30 o'clock using the transtibial technique and at the 10:30 and 9:30 o'clock using the AM portal technique. Then, for each femoral tunnel via the transtibial technique at 11:30, 10:30, and 9:30 o'clock positions, tests were performed for 3 directions of Rigidfix pin insertion using the lateral epicondyle as an anatomical landmark, namely, 15 degrees anterior to posterior (A-P), neutral, and 15 degrees posterior to anterior (P-A). It was then determined whether pins protruded from the posterior cortex. RESULTS: The lengths of femoral tunnels produced using the transtibial technique became shorter as the femoral starting position became more horizontal (51.1 mm, 40.0 mm, and 34.2 mm on average at the 11:30, 10:30, and 9:30 o'clock position, respectively). Tunnels made using the AM portal technique were significantly shorter than those made using the transtibial technique: by 7.6 mm at the 10:30 o'clock and 4.5 mm at the 9:30 o'clock positions on average (P < .001). In addition, increasing obliquity increased the likelihood of Rigidfix pin protrusion, especially when pins were inserted in the A-P direction. CONCLUSION: The current effort to lower the femoral tunnel position in ACL reconstruction can shorten the tunnel length and compromise the graft fixation at the femur using the Rigidfix system. CLINICAL RELEVANCE: When an intended femoral tunnel position is more horizontal than the 10:30 o'clock position for ACL reconstruction, a surgeon needs to be cautious regarding a short femoral tunnel, particularly when using the AM portal technique, and possible protrusion of the cross-pin (Rigidfix) fixator. PMID- 20348284 TI - Single- versus double-bundle posterior cruciate ligament reconstruction: effects of femoral tunnel separation. AB - BACKGROUND: Double-bundle posterior cruciate ligament reconstructions are performed to more closely replicate the anatomy of the native posterior cruciate ligament and to better restore normal knee biomechanics and kinematics than a single graft. The femoral tunnel for the anterolateral graft is normally located near the anterior margin of the posterior cruciate ligament footprint. However, there is considerable variability with regard to placement of the posteromedial tunnel within the footprint margins. HYPOTHESIS: A double-bundle posterior cruciate ligament reconstruction will better replicate normal knee biomechanics and kinematics than a single anterolateral graft, and the separation distance between femoral tunnels will significantly affect the recorded measurements. STUDY DESIGN: Controlled laboratory study. METHODS: The posterior cruciate ligament's femoral origin was mechanically isolated using a cylindrical coring cutter, and a cap of bone containing the ligament fibers was attached to a load cell that recorded resultant force in the posterior cruciate ligament as the knee was loaded. Cast acrylic replicas of the femoral bone cap, with 9-mm and 6-mm holes for the anterolateral and posteromedial grafts, respectively, were attached to the load cell. Graft isometries, anterior-posterior laxities, graft forces, and tibial rotations were measured for an anterolateral graft alone, and for anterolateral and posteromedial grafts with narrow (0-mm) and wide (3-mm) bridges between tunnels. RESULTS: Mean laxities with an anterolateral graft alone were within 1.2 mm of normal, between 0 degrees and 90 degrees; means with double bundle grafts were 1.7 mm to 2.4 mm less than normal, between 10 degrees and 45 degrees. Relative length change of the anterolateral graft between 0 degrees and 90 degrees was within +1.3 mm, while the posteromedial graft, placed in either tunnel, tightened approximately 6 mm with knee extension from 90 degrees to 0 degrees. At 0 degrees, mean forces with a single anterolateral graft were not significantly different from posterior cruciate ligament forces for any loading mode tested; mean forces with double-bundle grafts were 74 N to 154 N higher than posterior cruciate ligament forces at 0 degrees . During passive knee extension, the double-bundle reconstruction externally rotated the tibia (relative to intact) between 0 degrees and 50 degrees. There were no significant differences in mean knee laxities, graft forces, or tibial rotations between narrow and wide tunnel separations. CONCLUSION: In contrast to the anterolateral graft, which experienced minimal length changes, the posteromedial graft tightened 3.1 mm to 4.3 mm from 30 degrees to 0 degrees. When the posteromedial graft was tensioned and fixed at 30 degrees, it developed relatively high graft forces as the knee was extended to 0 degrees ; this tended to reduce knee laxity and increase graft forces. With double-bundle grafts, tunnel separation distance was not an important variable with respect to the biomechanical and kinematic measurements recorded in this study. CLINICAL RELEVANCE: The need for a posteromedial graft during posterior cruciate ligament reconstruction is questioned, especially in view of the relatively high graft forces at full extension that could cause it to permanently elongate with time. If a double-bundle reconstruction is performed, there is no biomechanical advantage in making the bone bridge between tunnels less than 3 mm. PMID- 20348285 TI - Chondrotoxicity of low pH, epinephrine, and preservatives found in local anesthetics containing epinephrine. AB - BACKGROUND: Recent clinical and basic science investigations have revealed the chondrotoxicity of local anesthetics, especially those containing epinephrine, administered via an intra-articular pain pump. However, the exact mechanism of toxicity is unknown. This study evaluates the chondrotoxicity of low pH, epinephrine, and preservatives found in commonly used local anesthetics. HYPOTHESIS: The chondrotoxicity of local anesthetics containing epinephrine is due to low pH, epinephrine, or the preservative sodium metabisulfite. STUDY DESIGN: Controlled laboratory study. METHODS: Human chondrocytes were harvested and cultured in a custom bioreactor designed to simulate metabolism of medication. Pain pumps were used to infuse one of the following medications into the culture system: control media; media titrated to pH 4.5, 5.0, 5.5, 6.0, 6.5; media with 1:100000 or 1:200000 epinephrine only; media with 0.5 mg/mL of sodium metabisulfite preservative; media with 0.5 mg/mL of methylparaben preservative, 0.25% bupivacaine, 0.25% bupivacaine with epinephrine, 1% lidocaine, and 1% lidocaine with epinephrine. Cultures were perfused for 24 hours and then were stained with live/dead cell viability assay. The chondrocytes were then examined by fluorescence microscopy and counted, and the percentage of cell death was calculated. RESULTS: Cultures containing media titrated to pH 4.5 and 5.0 and local anesthetics containing epinephrine (pH 4.0-5.5) had high cell death rates compared with controls at all time points (P < .001), while cultures containing 1:100000 and 1:200000 epinephrine alone had no increased death rate. Also, 0.5 mg/mL sodium metabisulfite preservative had a significant effect on cell death (P < .034); however, the preservative methylparaben had no effect (P > .05). The percentage of cell death was not significant for 1% lidocaine (12.5%; P > .943) and 0.25% bupivacaine (16.5%; P > .609). CONCLUSION: The marked chondrotoxicity of local anesthetics containing epinephrine appears to be a combined effect of low pH, as these medications are titrated to pH 4.0 to 5.5 for product stability, and the preservative sodium metabisulfite. Extreme caution should be exercised when using intra-articular pain pumps with local anesthetics containing epinephrine. CLINICAL RELEVANCE: Understanding the causes of chondrotoxicity using local anesthetics containing epinephrine is critical to decrease complications associated with this class of medications. PMID- 20348286 TI - Deep venous thrombosis of the axillary and subclavian vein after osteosynthesis of a midshaft clavicular fracture: a case report. PMID- 20348287 TI - Management of the metabolic syndrome in patients with human immunodeficiency virus. AB - Patients with human immunodeficiency virus (HIV) are an increasing subpopulation of patients seen in endocrine/diabetes clinics. This article explores evidence based treatment recommendations for patients with metabolic syndrome who are also positive for HIV. Patients infected with HIV may manifest metabolic abnormalities. They often present with low high-density lipoprotein (HDL-C), hypertension, visceral adiposity, and insulin resistance, among other symptoms consistent with features of the metabolic syndrome. The etiologies of the metabolic abnormalities are not completely understood. The role of highly active antiretroviral therapy (HAART) and the separate effect of HIV on patients who are surviving longer may contribute to the increased incidence of the development of the metabolic syndrome. The role of the health care team is to provide patient education to patients with HIV concerning lifestyle modification in order to prevent complications related to the metabolic syndrome. PMID- 20348288 TI - PCR-denaturing gradient gel electrophoresis analysis to assess the effects of a genetically modified cucumber mosaic virus-resistant tomato plant on soil microbial communities. AB - The effects of a genetically modified cucumber mosaic virus (CMV)-resistant tomato on soil microbial communities were evaluated in this study. Soil position and environmental factors played more dominant roles than the tomato genotype in the variation of soil microbial communities. PMID- 20348289 TI - Relative decay of Bacteroidales microbial source tracking markers and cultivated Escherichia coli in freshwater microcosms. AB - Fecal indicator bacteria (FIB), commonly used to regulate sanitary water quality, cannot discriminate among sources of contamination. The use of alternative quantitative PCR (qPCR) methods for monitoring fecal contamination or microbial source tracking requires an understanding of relationships with cultivated FIB, as contamination ages under various conditions in the environment. In this study, the decay rates of three Bacteroidales 16S rRNA gene markers (AllBac for general contamination and qHF183 and BacHum for human-associated contamination) were compared with the decay rate of cultivated Escherichia coli in river water microcosms spiked with human wastewater. The following five sets of microcosms were monitored over 11 days: control, artificial sunlight, sediment exposure, reduced temperature, and no autochthonous predation. Decay was characterized by estimation of the time needed to produce a 2-log reduction (t(99)). No treatment associated differences in the decay of the 4 targets were evident except with reduced predation, where E. coli, qHF183, and BacHum markers had lower levels of decay by day 3. However, there were substantial target-associated differences. Decay curves for the AllBac marker indicated a larger persistent population than those of the other targets. Exposure to sunlight, sediment, and reduced predation resulted in more rapid decay of the human-associated markers relative to cultivable E. coli, but there were no differences in t(99) values among the 4 targets under control conditions or at reduced temperatures. Further evaluation of epidemiological relationships will be needed in order to relate the markers directly to health risk. These findings suggest that the tested human-associated markers can complement E. coli as indicators of the human impact on sanitary water quality under the constrained conditions described in this paper. PMID- 20348290 TI - Comparative transcriptomic and phenotypic analysis of the responses of Bacillus cereus to various disinfectant treatments. AB - Antimicrobial chemicals are widely applied to clean and disinfect food-contacting surfaces. However, the cellular response of bacteria to various disinfectants is unclear. In this study, the physiological and genome-wide transcriptional responses of Bacillus cereus ATCC 14579 exposed to four different disinfectants (benzalkonium chloride, sodium hypochlorite, hydrogen peroxide, and peracetic acid) were analyzed. For each disinfectant, concentrations leading to the attenuation of growth, growth arrest, and cell death were determined. The transcriptome analysis revealed that B. cereus, upon exposure to the selected concentrations of disinfectants, induced common and specific responses. Notably, the common response included genes involved in the general and oxidative stress responses. Exposure to benzalkonium chloride, a disinfectant known to induce membrane damage, specifically induced genes involved in fatty acid metabolism. Membrane damage induced by benzalkonium chloride was confirmed by fluorescence microscopy, and fatty acid analysis revealed modulation of the fatty acid composition of the cell membrane. Exposure to sodium hypochlorite induced genes involved in metabolism of sulfur and sulfur-containing amino acids, which correlated with the excessive oxidation of sulfhydryl groups observed in sodium hypochlorite-stressed cells. Exposures to hydrogen peroxide and peracetic acid induced highly similar responses, including the upregulation of genes involved in DNA damage repair and SOS response. Notably, hydrogen peroxide- and peracetic acid-treated cells exhibited high mutation rates correlating with the induced SOS response. PMID- 20348291 TI - Cloning of separate meilingmycin biosynthesis gene clusters by use of acyltransferase-ketoreductase didomain PCR amplification. AB - Five meilingmycins, A to E, with A as the major component, were isolated from Streptomyces nanchangensis NS3226. Through nuclear magnetic resonance (NMR) characterization, meilingmycins A to E proved to be identical to reported milbemycins alpha11, alpha13, alpha14, beta1, and beta9, respectively. Sequencing of a previously cloned 103-kb region identified three modular type I polyketide synthase genes putatively encoding the last 11 elongation steps, three modification proteins, and one transcriptional regulatory protein for meilingmycin biosynthesis. However, the expected loading module and the first two elongation modules were missing. In meilingmycin, the presence of a methyl group at C-24 and a hydroxyl group at C-25 suggests that the elongation module 1 contains a methylmalonyl-coenzyme A (CoA)-specific acyltransferase (ATp) domain and a ketoreductase (KR) domain. Based on the conserved motifs of the ATp and KR domains, a pair of primers was designed for PCR amplification, and a 1.40-kb expected fragment was amplified, whose sequence shows significant homology with the elongation module 1 of the aveA1-encoded enzyme AVES1. A polyketide synthase (PKS) gene encoding one loading and two elongation modules, with a downstream C-5 O-methyltransferase gene, meiD, was subsequently localized 55 kb apart from the previously sequenced region, and its deletion abolishes meilingmycin production. A series of deletions within the 55-kb intercluster region rules out its involvement in meilingmycin biosynthesis. Furthermore, gene deletion of meiD eliminates meilingmycins D and E, with methyls at C-5. Our work provides a more specific strategy for the cloning of modular type I PKS gene clusters. The cloning of the meilingmycin gene clusters paves the way for its pathway engineering. PMID- 20348292 TI - HypC, the anthrone oxidase involved in aflatoxin biosynthesis. AB - On the basis of gene disruption and enzyme activity, hypC, an open reading frame in the region between the pksA (aflC) and nor-1 (aflD) genes in the aflatoxin biosynthesis gene cluster, encodes a 17-kDa oxidase that converts norsolorinic acid anthrone to norsolorinic acid. PMID- 20348293 TI - Spatially resolved characterization of water and ion incorporation in Bacillus spores. AB - We present the first direct visualization and quantification of water and ion uptake into the core of individual dormant Bacillus thuringiensis subsp. israelensis (B. thuringiensis subsp. israelensis) endospores. Isotopic and elemental gradients in the B. thuringiensis subsp. israelensis spores show the permeation and incorporation of deuterium in deuterated water (D(2)O) and solvated ions throughout individual spores, including the spore core. Under hydrated conditions, incorporation into a spore occurs on a time scale of minutes, with subsequent uptake of the permeating species continuing over a period of days. The distribution of available adsorption sites is shown to vary with the permeating species. Adsorption sites for Li(+), Cs(+), and Cl(-) are more abundant within the spore outer structures (exosporium, coat, and cortex) relative to the core, while F(-) adsorption sites are more abundant in the core. The results presented here demonstrate that elemental abundance and distribution in dormant spores are influenced by the ambient environment. As such, this study highlights the importance of understanding how microbial elemental and isotopic signatures can be altered postproduction, including during sample preparation for analysis, and therefore, this study is immediately relevant to the use of elemental and isotopic markers in environmental microbiology and microbial forensics. PMID- 20348294 TI - New method for monitoring programmed cell death and differentiation in submerged Streptomyces cultures. AB - Vital stains were used in combination with fluorimetry for the elaboration of a new method to quantify Streptomyces programmed cell death, one of the key events in Streptomyces differentiation. The experimental approach described opens the possibility of designing online protocols for automatic monitoring of industrial fermentations. PMID- 20348295 TI - Efficient electrotransformation of Bacteroides fragilis. AB - This study describes refined electroporation parameters for efficient transformation of Bacteroides fragilis by plasmids prepared from laboratory strains of Escherichia coli. Development of the method used included determination of the optimal growth conditions for competent cell preparation, selectable antimicrobial resistance markers, electric field strength, and postpulse incubation time. Of the four E. coli-Bacteroides shuttle plasmids tested (pVAL-1, pVAL-2, pNLY1, and pLYL05), pLYL05 containing the cefoxitin resistance marker was found to be the most suitable for B. fragilis transformation, and it generated 2- to 900-fold more transformants (about 10(4) transformants per microg pLYL05 DNA) than the other plasmids. For the 72-h cultivation period tested, B. fragilis cells harvested at 48 h yielded the highest numbers of transformants. The transformation efficiency of pLYL05 increased linearly with the electric field strength over a range from 5.0 to 12.5 kV/cm. At least 3 h of postpulse incubation was required to maximize the transformation efficiency. For deletion of B. fragilis genes by homologous recombination, competent cells grown to early exponential phase and 12 h of postpulse incubation were required for efficient integration of the pLYL05-based suicide vector into the target site. The expected integration was obtained in B. fragilis strain NCTC9343 only when a homologously prepared (i.e., in vivo methylated) suicide vector was used. Spontaneous resolution of the diploid successfully deleted the expected genetic region. Our simple and efficient plasmid transfer method enabled disruption of a B. fragilis gene using in vivo methylated targeted vectors. Our optimized electroporation parameters provide a useful tool for genetic manipulation of Bacteroides species. PMID- 20348296 TI - Characterization of the serpin-encoding gene of Bifidobacterium breve 210B. AB - Members of the serpin (serine protease inhibitor) superfamily have been identified in higher multicellular eukaryotes, as well as in bacteria, although examination of available genome sequences has indicated that homologs of the bacterial serpin-encoding gene (ser) are not widely distributed. In members of the genus Bifidobacterium this gene appears to be present in at least 5, and perhaps up to 9, of the 30 species tested. Moreover, phylogenetic analysis using available bacterial and eukaryotic serpin sequences revealed that bifidobacteria produce serpins that form a separate clade. We characterized the ser(210B) locus of Bifidobacterium breve 210B, which encompasses a number of genes whose deduced protein products display significant similarity to proteins encoded by corresponding loci found in several other bifidobacteria. Northern hybridization, primer extension, microarray, reverse transcription-PCR (RT-PCR), and quantitative real-time PCR (qRT-PCR) analyses revealed that a 3.5-kb polycistronic mRNA encompassing the ser(210B) operon with a single transcriptional start site is strongly induced following treatment of B. breve 210B cultures with some proteases. Interestingly, transcription of other bifidobacterial ser homologs appears to be triggered by different proteases. PMID- 20348297 TI - Considerable increase in resveratrol production by recombinant industrial yeast strains with use of rich medium. AB - Resveratrol synthesis from p-coumarate was analyzed in different Saccharomyces cerevisiae strains expressing the 4-coumaroyl-coenzyme A ligase (4CL1) from Arabidopsis thaliana and the stilbene synthase (STS) from Vitis vinifera and compared between yeast cultures growing in rich or synthetic medium. The use of rich medium considerably improved resveratrol production, and resveratrol yields of up to 391 mg/liter could be achieved with an industrial Brazilian sugar cane fermenting yeast. PMID- 20348298 TI - Proteomic analyses to reveal the protective role of glutathione in resistance of Lactococcus lactis to osmotic stress. AB - Previously, we have shown that glutathione can protect Lactococcus lactis against oxidative stress and acid stress. In this study, we show that glutathione taken up by L. lactis SK11 can protect this organism against osmotic stress. When exposed to 5 M NaCl, L. lactis SK11 cells containing glutathione exhibited significantly improved survival compared to the control cells. Transmission electron microscopy showed that the integrity of L. lactis SK11 cells containing glutathione was maintained for at least 24 h, whereas autolysis of the control cells occurred within 2 h after exposure to this osmotic stress. Comparative proteomic analyses using SK11 cells containing or not containing glutathione that were exposed or not exposed to osmotic stress were performed. The results revealed that 21 of 29 differentially expressed proteins are involved in metabolic pathways, mainly sugar metabolism. Several glycolytic enzymes of L. lactis were significantly upregulated in the presence of glutathione, which might be the key for improving the general stress resistance of a strain. Together with the results of previous studies, the results of this study demonstrated that glutathione plays important roles in protecting L. lactis against multiple environmental stresses; thus, glutathione can be considered a general protectant for improving the robustness and stability of dairy starter cultures. PMID- 20348299 TI - Genetic basis of tetracycline resistance in Bifidobacterium animalis subsp. lactis. AB - All strains of Bifidobacterium animalis subsp. lactis described to date show medium level resistance to tetracycline. Screening of 26 strains from a variety of sources revealed the presence of tet(W) in all isolates. A transposase gene upstream of tet(W) was found in all strains, and both genes were cotranscribed in strain IPLAIC4. Mutants with increased tetracycline resistance as well as tetracycline-sensitive mutants of IPLAIC4 were isolated and genetically characterized. The native tet(W) gene was able to restore the resistance phenotype to a mutant with an alteration in tet(W) by functional complementation, indicating that tet(W) is necessary and sufficient for the tetracycline resistance seen in B. animalis subsp. lactis. PMID- 20348300 TI - Use of the yeast Pichia pastoris as an expression host for secretion of enterocin L50, a leaderless two-peptide (L50A and L50B) bacteriocin from Enterococcus faecium L50. AB - In this work, we report the expression and secretion of the leaderless two peptide (EntL50A and EntL50B) bacteriocin enterocin L50 from Enterococcus faecium L50 by the methylotrophic yeast Pichia pastoris X-33. The bacteriocin structural genes entL50A and entL50B were fused to the Saccharomyces cerevisiae gene region encoding the mating pheromone alpha-factor 1 secretion signal (MFalpha1(s)) and cloned, separately and together (entL50AB), into the P. pastoris expression and secretion vector pPICZalphaA, which contains the methanol-inducible alcohol oxidase promoter (P(AOX1)) to express the fusion genes. After transfer into the yeast, the recombinant plasmids were integrated into the genome, resulting in three bacteriocinogenic yeast strains able to produce and secrete the individual bacteriocin peptides EntL50A and EntL50B separately and together. The secretion was efficiently directed by MFalpha1(s) through the Sec system, and the precursor peptides were found to be correctly processed to form mature and active bacteriocin peptides. The present work describes for the first time the heterologous expression and secretion of a two-peptide non-pediocin-like bacteriocin by a yeast. PMID- 20348301 TI - Effects of environmental stress on stability of tandem repeats in Escherichia coli O157:H7. AB - Multilocus variable-number tandem-repeat analysis (MLVA) is used for source tracking Escherichia coli O157:H7 in agricultural environments. Tandem repeats were stable after limited replication but changed after exposure to irradiation, elevated temperatures, and starvation conditions. The pO157 plasmid was frequently lost under these stress conditions. Environmental stresses may increase phylogenetic diversity as measured by MLVA. PMID- 20348302 TI - Subsurface cycling of nitrogen and anaerobic aromatic hydrocarbon biodegradation revealed by nucleic Acid and metabolic biomarkers. AB - Microbial processes are crucial for ecosystem maintenance, yet documentation of these processes in complex open field sites is challenging. Here we used a multidisciplinary strategy (site geochemistry, laboratory biodegradation assays, and field extraction of molecular biomarkers) to deduce an ongoing linkage between aromatic hydrocarbon biodegradation and nitrogen cycling in a contaminated subsurface site. Three site wells were monitored over a 10-month period, which revealed fluctuating concentrations of nitrate, ammonia, sulfate, sulfide, methane, and other constituents. Biodegradation assays performed under multiple redox conditions indicated that naphthalene metabolism was favored under aerobic conditions. To explore in situ field processes, we measured metabolites of anaerobic naphthalene metabolism and expressed mRNA transcripts selected to document aerobic and anaerobic microbial transformations of ammonia, nitrate, and methylated aromatic contaminants. Gas chromatography-mass spectrometry detection of two carboxylated naphthalene metabolites and transcribed benzylsuccinate synthase, cytochrome c nitrite reductase, and ammonia monooxygenase genes indicated that anaerobic metabolism of aromatic compounds and both dissimilatory nitrate reduction to ammonia (DNRA) and nitrification occurred in situ. These data link formation (via DNRA) and destruction (via nitrification) of ammonia to in situ cycling of nitrogen in this subsurface habitat, where metabolism of aromatic pollutants has led to accumulation of reduced metabolic end products (e.g., ammonia and methane). PMID- 20348303 TI - Interplay between Clostridium thermocellum family 48 and family 9 cellulases in cellulosomal versus noncellulosomal states. AB - The anaerobic, thermophilic cellulolytic bacterium Clostridium thermocellum is known for its elaborate cellulosome complex, but it also produces a separate free cellulase system. Among the free enzymes, the noncellulosomal enzyme Cel9I is a processive endoglucanase whose sequence and architecture are very similar to those of the cellulosomal enzyme Cel9R; likewise, the noncellulosomal exoglucanase Cel48Y is analogous to the principal cellulosomal enzyme Cel48S. In this study we used the designer cellulosome approach to examine the interplay of prominent cellulosomal and noncellulosomal cellulases from C. thermocellum. Toward this end, we converted the cellulosomal enzymes to noncellulosomal chimeras by swapping the dockerin module of the cellulosomal enzymes with a carbohydrate-binding module from the free enzyme analogues and vice versa. This enabled us to study the importance of the targeting effect of the free enzymes due to their carbohydrate-binding module and the proximity effect for cellulases on the designer cellulosome. C. thermocellum is the only cellulosome-producing bacterium known to express two different glycoside hydrolase family 48 enzymes and thus the only bacterial system that can currently be used for such studies. The different activities with crystalline cellulose were examined, and the results demonstrated that the individual chimeric cellulases were essentially equivalent to the corresponding wild-type analogues. The wild-type cellulases displayed a synergism of about 1.5-fold; the cellulosomal pair acted synergistically when they were converted into free enzymes, whereas the free enzymes acted synergistically mainly in the wild-type state. The targeting effect was found to be the major factor responsible for the elevated activity observed for these specific enzyme combinations, whereas the proximity effect appeared to play a negligible role. PMID- 20348304 TI - ArcS, the cognate sensor kinase in an atypical Arc system of Shewanella oneidensis MR-1. AB - The availability of oxygen is a major environmental factor for many microbes, in particular for bacteria such as Shewanella species, which thrive in redox stratified environments. One of the best-studied systems involved in mediating the response to changes in environmental oxygen levels is the Arc two-component system of Escherichia coli, consisting of the sensor kinase ArcB and the cognate response regulator ArcA. An ArcA ortholog was previously identified in Shewanella, and as in Escherichia coli, Shewanella ArcA is involved in regulating the response to shifts in oxygen levels. Here, we identified the hybrid sensor kinase SO_0577, now designated ArcS, as the previously elusive cognate sensor kinase of the Arc system in Shewanella oneidensis MR-1. Phenotypic mutant characterization, transcriptomic analysis, protein-protein interaction, and phosphotransfer studies revealed that the Shewanella Arc system consists of the sensor kinase ArcS, the single phosphotransfer domain protein HptA, and the response regulator ArcA. Phylogenetic analyses suggest that HptA might be a relict of ArcB. Conversely, ArcS is substantially different with respect to overall sequence homologies and domain organizations. Thus, we speculate that ArcS might have adopted the role of ArcB after a loss of the original sensor kinase, perhaps as a consequence of regulatory adaptation to a redox-stratified environment. PMID- 20348305 TI - In silico identification of gene amplification targets for improvement of lycopene production. AB - The identification of genes to be deleted or amplified is an essential step in metabolic engineering for strain improvement toward the enhanced production of desired bioproducts. In the past, several methods based on flux analysis of genome-scale metabolic models have been developed for identifying gene targets for deletion. Genome-wide identification of gene targets for amplification, on the other hand, has been rather difficult. Here, we report a strategy called flux scanning based on enforced objective flux (FSEOF) to identify gene amplification targets. FSEOF scans all the metabolic fluxes in the metabolic model and selects fluxes that increase when the flux toward product formation is enforced as an additional constraint during flux analysis. This strategy was successfully employed for the identification of gene amplification targets for the enhanced production of the red-colored antioxidant lycopene. Additional metabolic engineering based on gene knockout simulation resulted in further synergistic enhancement of lycopene production. Thus, FSEOF can be used as a general strategy for selecting genome-wide gene amplification targets in silico. PMID- 20348306 TI - Effect of DNA extraction method on the apparent microbial diversity of soil. AB - Four extraction methods, including a novel one, were compared for their efficiencies in producing DNA from three contrasting agricultural soils. Molecular analyses (PCR-denaturing gradient gel electrophoresis [DGGE] and clone libraries) focusing on different microbial groups were used as assessment criteria. Per soil, the DNA yields differed between extraction methods. Clear effects of method on apparent richness and community structure were found. Actinobacterial diversity based on soil DNA produced by two divergent methods revealed that a hitherto-undescribed group was obtained by the novel method. PMID- 20348307 TI - Expression in Escherichia coli of the native cyt1Aa from Bacillus thuringiensis subsp. israelensis. AB - The gene cyt1Aa is one of the genes in the complex determining the mosquito larvicidity of Bacillus thuringiensis subsp. israelensis. Previous cloning in Escherichia coli resulted in a 48-bp addition upstream, encoding a chimera. Here, cyt1Aa was recloned without the artifact, and its toxicity against Aedes aegypti larvae and host E. coli cells was retested. PMID- 20348308 TI - The internal transcribed spacer region, a new tool for use in species differentiation and delineation of systematic relationships within the Campylobacter genus. AB - The Campylobacter genus consists of a number of important human and animal pathogens. Although the 16S rRNA gene has been used extensively for detection and identification of Campylobacter species, there is currently limited information on the 23S rRNA gene and the internal transcribed spacer (ITS) region that lies between the 16S and 23S rRNA genes. We examined the potential of the 23S rRNA gene and the ITS region to be used in species differentiation and delineation of systematic relationships for 30 taxa within the Campylobacter genus. The ITS region produced the highest mean pairwise percentage difference (35.94%) compared to the 16S (5.34%) and 23S (7.29%) rRNA genes. The discriminatory power for each region was further validated using Simpson's index of diversity (D value). The D values were 0.968, 0.995, and 0.766 for the ITS region and the 23S and 16S rRNA genes, respectively. A closer examination of the ITS region revealed that Campylobacter concisus, Campylobacter showae, and Campylobacter fetus subsp. fetus harbored tRNA configurations not previously reported for other members of the Campylobacter genus. We also observed the presence of strain-dependent intervening sequences in the 23S rRNA genes. Neighbor-joining trees using the ITS region revealed that Campylobacter jejuni and Campylobacter coli strains clustered in subgroups, which was not observed in trees derived from the 16S or 23S rRNA gene. Of the three regions examined, the ITS region is by far the most cost-effective region for the differentiation and delineation of systematic relationships within the Campylobacter genus. PMID- 20348310 TI - Risk of Listeria monocytogenes contamination of raw ready-to-eat seafood products available at retail outlets in Japan. AB - Examination of Listeria monocytogenes prevalence among ready-to-eat foods in Japan revealed frequent (5.7 to 12.1%) contamination of minced tuna and fish roe products, and the isolates had the same virulence levels as clinical isolates in terms of invasion efficiency and infectivity in cell cultures and a murine infection model, respectively. Premature stop codons in inlA were infrequent (1 out of 39 isolates). Cell numbers of L. monocytogenes in minced tuna and salmon roe increased rapidly under inappropriate storage temperatures (from a most probable number [MPN] of 10(0) to 10(1)/g to an MPN of 10(3) to 10(4)/g over the course of 2 days at 10 degrees C). Thus, regulatory guidelines are needed for acceptable levels of L. monocytogenes in these foods. PMID- 20348309 TI - Different atmospheric methane-oxidizing communities in European beech and Norway spruce soils. AB - Norway spruce (Picea abies) forests exhibit lower annual atmospheric methane consumption rates than do European beech (Fagus sylvatica) forests. In the current study, pmoA (encoding a subunit of membrane-bound CH(4) monooxygenase) genes from three temperate forest ecosystems with both beech and spruce stands were analyzed to assess the potential effect of tree species on methanotrophic communities. A pmoA sequence difference of 7% at the derived protein level correlated with the species-level distance cutoff value of 3% based on the 16S rRNA gene. Applying this distance cutoff, higher numbers of species-level pmoA genotypes were detected in beech than in spruce soil samples, all affiliating with upland soil cluster alpha (USCalpha). Additionally, two deep-branching genotypes (named 6 and 7) were present in various soil samples not affiliating with pmoA or amoA. Abundance of USCalpha pmoA genes was higher in beech soils and reached up to (1.2 +/- 0.2) x 10(8) pmoA genes per g of dry weight. Calculated atmospheric methane oxidation rates per cell yielded the same trend. However, these values were below the theoretical threshold necessary for facilitating cell maintenance, suggesting that USCalpha species might require alternative carbon or energy sources to thrive in forest soils. These collective results indicate that the methanotrophic diversity and abundance in spruce soils are lower than those of beech soils, suggesting that tree species-related factors might influence the in situ activity of methanotrophs. PMID- 20348311 TI - Development of a conditional gene expression system using a zearalenone-inducible promoter for the ascomycete fungus Gibberella zeae. AB - The ascomycete fungus Gibberella zeae is an important plant pathogen that causes fusarium head blight on small grains. Molecular studies of this fungus have been performed extensively to uncover the biological mechanisms related to pathogenicity, toxin production, and sexual reproduction. Molecular methods, such as targeted gene deletion, gene overexpression, and gene fusion to green fluorescent protein (GFP), are relatively easy to perform with this fungus; however, conditional expression systems have not been developed. The purpose of this study was to identify a promoter that could be induced by zearalenone (ZEA) for the development of a conditional expression system in G. zeae. Through microarray analysis, we isolated one zearalenone response gene (ZEAR) whose expression was increased more than 50 times after ZEA treatment. Northern blot analysis showed that the ZEAR transcript dramatically increased after 1 h of ZEA treatment. To determine the utility of the ZEAR promoter, called Pzear, in a conditional expression system, we transformed a Pzear::GFP fusion construct into G. zeae. Our data showed a ZEA concentration-dependent increase in GFP expression. We also replaced the promoter of G. zeae metE (GzmetE), an essential gene for methionine biosynthesis, with the Pzear promoter. The growth of the Pzear-GzmetE mutant on minimal medium was dependent on the ZEA concentration supplemented in the medium and showed that GzMetE expression was induced by ZEA. This study is the first report of an inducible promoter in G. zeae. Our system will be useful for the characterization of essential gene functions in this fungus through differential and ZEA-dependent gene expression. In addition, the Pzear promoter may be applicable as a biosensor for the detection of ZEA contamination in agricultural products. PMID- 20348312 TI - Construction of aminoglycoside-sensitive Burkholderia cenocepacia strains for use in studies of intracellular bacteria with the gentamicin protection assay. AB - Burkholderia cenocepacia is a multidrug-resistant opportunistic pathogen that infects the airways of patients with cystic fibrosis (CF) and can survive intracellularly in macrophages and epithelial cells. The gentamicin protection assay, which relies on the poor ability of gentamicin or other aminoglycosides to permeate eukaryotic cell membranes, is traditionally employed to quantify intracellular bacteria. However, the high resistance of these bacteria to aminoglycosides hampers the use of the gentamicin protection assay to investigate intracellular infection by B. cenocepacia. Here, we report the construction of gentamicin-sensitive strains of B. cenocepacia carrying a deletion of the BCAL1674, BCAL1675, and BCAL1676 genes that form an operon encoding an AmrAB-OprA like efflux pump. We show that bacteria carrying this deletion are hypersensitive to gentamicin and also delay phagolysosomal fusion upon infection of RAW 264.7 murine macrophages, as previously demonstrated for the parental strain. We also demonstrate for the first time that low concentrations of gentamicin can be used to effectively kill extracellular bacteria and reliably quantify the intracellular infection by B. cenocepacia, which can replicate in RAW 264.7 macrophages. PMID- 20348313 TI - Poor invasion of trophoblastic cells but normal plaque formation in fibroblastic cells despite actA deletion in a group of Listeria monocytogenes strains persisting in some food processing environments. AB - We determined mammalian cell invasion and virulence gene (inlA, inlB, and actA) sequences of Listeria monocytogenes strains belonging to a molecular subtype (RAPD 9) that often persists in Danish fish-processing plants. These strains invaded human placental trophoblasts less efficiently than other L. monocytogenes strains, including clinical strains, and they carry a premature stop codon in inlA. Eight of 15 strains, including the RAPD 9 and maternofetal strains, had a 105-nucleotide deletion in actA that did not affect cell-to-cell spread in mouse fibroblasts. The RAPD 9 strains may still be regarded as of low virulence with respect to human listeriosis. PMID- 20348314 TI - The transcriptional repressor FarR is not involved in meningococcal fatty acid resistance mediated by the FarAB efflux pump and dependent on lipopolysaccharide structure. AB - Free fatty acids are important antimicrobial substances regulating the homeostasis of colonizing bacteria on epithelial surfaces. Here, we show that meningococci express a functional farAB efflux pump, which is indispensable for fatty acid resistance. However, other than in Neisseria gonorrhoeae, the transcriptional regulator FarR is not involved in regulation of this operon in Neisseria meningitidis. We tested the susceptibility of 23 meningococcal isolates against saturated and unsaturated long-chain fatty acids, proving that meningococci are generally highly resistant, with the exception of serogroup Y strains belonging to sequence type 23. Using genetically determined lipopolysaccharide (LPS)-truncated mutant strains, we show that addition of the LPS core oligosaccharide and hexa-acylation of its membrane anchor lipid A are imperative for fatty acid resistance of meningococci. The sensitivity of the serogroup Y strains is due to naturally occurring mutations within the lpxL1 gene, which is responsible for addition of the sixth acyl chain on the LPS membrane anchor lipid A. Therefore, fatty acid resistance in meningococci is provided by both the active efflux pump FarAB and by the natural permeability barrier of the Gram-negative outer membrane. The transcriptional regulator FarR is not implicated in fatty acid resistance in meningococci, possibly giving rise to a constitutively active FarAB efflux pump system and thus revealing diverse mechanisms of niche adaptation in the two closely related Neisseria species. PMID- 20348315 TI - Nocardia niwae sp. nov., isolated from human pulmonary sources. AB - Members of the genus Nocardia are responsible for cutaneous, pulmonary and disseminated human infections. From 2003 to 2008, four nocardioform strains (W8027, W8681, W9071 and W9241(T)) were isolated from patients in the state of Florida, USA. Ribosomal gene sequencing analysis suggested that a novel species of the genus Nocardia had been isolated. These strains were subjected to a taxonomic analysis using a polyphasic approach. Phenotypic analyses included morphological examination, biochemical profiling and antimicrobial susceptibility testing. Molecular studies included 16S rRNA and DNA gyrase B subunit (gyrB) gene sequence analyses and DNA-DNA hybridization. Phylogenetic neighbours were determined through 16S rRNA and gyrB gene sequence analyses. Phenotypic characteristics that differentiated the novel isolates from phylogenetically related species were growth at 45 degrees C, and three of the four novel strains utilized l-rhamnose. The antimicrobial profiles could not reliably distinguish the novel species from related nocardiae. Analysis showed that the 16S rRNA gene sequences of the four novel isolates were identical. The blast analysis of the near full-length 16S rRNA gene showed 99.2 % sequence similarity to Nocardia araoensis DSM 44729(T), Nocardia arthritidis DSM 44731(T) and Nocardia beijingensis JCM 10666(T), 98.7 % to Nocardia amamiensis DSM 45066(T), 98.2 % to Nocardia pneumoniae JCM 12119(T) and 97.8 % to Nocardia takedensis JCM 13313(T). Analysis of partial gyrB gene sequences showed that the novel isolates had 95.4 % similarity to N. arthritidis DSM 44731(T), 95.3 % to Nocardia gamkensis DSM 44956(T), 94.4 % to N. pneumoniae JCM 12119(T), 93.8 % to Nocardia asiatica DSM 44668(T), 93.5 % to N. amamiensis DSM 45066(T), 93.4 % to N. beijingensis JCM 10666(T) and 93.2 % to N. araoensis DSM 44729(T). The DNA-DNA relatedness values between the four novel strains were 86-89 %; the relatedness value for strain W9241(T) compared with N. beijingensis JCM 10666(T) was 47 % and 46 % with N. araoensis DSM 44729(T), 44 % with N. arthritidis DSM 44731(T), 32 % with N. amamiensis DSM 45066(T) and 20 % with N. asiatica DSM 44668(T). The results of the taxonomic analysis suggested that the new isolates represent a novel species of the genus Nocardia for which the name Nocardia niwae sp. nov. is proposed. The type strain is W9241(T) (=DSM 45340(T)=CCUG 57756(T)). PMID- 20348316 TI - Sympodiomycopsis kandeliae sp. nov., a basidiomycetous anamorphic fungus from mangroves, and reclassification of Sympodiomycopsis lanaiensis as Jaminaea lanaiensis comb. nov. AB - Three ustilaginomycetous anamorphic strains were isolated from flowers of Kandelia candel in mangrove forests of Taiwan. Phylogenetic analyses based on the combined sequences of internal transcribed spacer 1 (ITS1)-5.8S-ITS2 and the D1/D2 domain of the large-subunit (LSU) rDNA indicated that the closest recognized species was Sympodiomycopsis paphiopedili. The results of a DNA-DNA hybridization experiment and the physiological characteristics showed that the three strains represent a novel species within the genus Sympodiomycopsis. The name Sympodiomycopsis kandeliae sp. nov. is proposed, with FIRDI 007(T) (=BCRC 23165(T) =CBS 11676(T)) as the type strain. In addition, based on phenotypic characteristics and the phylogenetic analyses of the combined sequences of the ITS region and D1/D2 domain of the LSU rDNA, Sympodiomycopsis lanaiensis was clustered with the genus Jaminaea. A new combination, Jaminaea lanaiensis comb. nov. (type strain LM418(T) =DSM 18755(T) =ATCC MYA-4092(T) =NRRL Y-48466(T) =CBS 10858(T) =BCRC 23177(T)), is proposed. PMID- 20348317 TI - Candida saraburiensis sp. nov. and Candida prachuapensis sp. nov., xylose utilizing yeast species isolated in Thailand. AB - Four strains of two novel xylose-utilizing yeast species were obtained from samples collected in Thailand from decaying corncobs (strains KU-Xs13(T) and KU Xs18), a decaying grass (KU-Xs20) and estuarine water from a mangrove forest (WB15(T)). On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics and sequence analysis of the D1/D2 domain of the large subunit rRNA gene, the four strains were found to represent two novel species of the genus Candida in the Candida albicans/Lodderomyces elongisporus clade. Three strains (KU-Xs13(T), KU-Xs18 and KU-Xs20) were assigned as a single novel species, which was named Candida saraburiensis sp. nov. The type strain is KU-Xs13(T) (=CBS 11696(T)=NBRC 106721(T)=BCC 39601(T)). Strain WB15(T) represented another novel species of the genus Candida that was named Candida prachuapensis sp. nov. The type strain is WB15(T) (=CBS 11024(T)=NBRC 104881(T)=BCC 29904(T)). PMID- 20348318 TI - Frateuria terrea sp. nov., isolated from forest soil, and emended description of the genus Frateuria. AB - A bacterial strain, designated VA24(T), was isolated from forest soil of the Changbai Mountains, Heilongjiang province, China. Cells of strain VA24(T) were Gram-reaction-negative, aerobic, non-spore-forming, long rods, 0.3-0.5*2.0-3.0 MUm in size and were motile by means of a subpolar flagellum. Strain VA24(T) was oxidase-positive and catalase-negative. Growth occurred at 21-36 degrees C, pH 5 10 and in 0-2 % (w/v) NaCl but did not occur at 37 degrees C. The predominant respiratory quinone was Q-8, the major polar lipids were phosphatidylethanolamine and phosphatidylmonomethylethanolamine and the major cellular fatty acids were iso-C(15 : 0) (14.9 %), iso-C(17 : 1)omega9c (14.1 %), iso-C(17 : 0) (10.8 %) and iso-C(16 : 0) (10.3 %). The DNA G+C content was 67.4 mol% (T(m)). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain VA24(T) was closely related to Frateuria aurantia IFO 13300(T) with 96.9 % sequence similarity. DNA-DNA relatedness of strain VA24(T) to F. aurantia DSM 6220(T) was 15.8 %. Based on its phenotypic and genotypic features, strain VA24(T) represents a novel species of the genus Frateuria, for which the name Frateuria terrea sp. nov. is proposed. The type strain is VA24(T) (=CGMCC 1.7053(T) =NBRC 104236(T)). PMID- 20348319 TI - Bacteroides paurosaccharolyticus sp. nov., isolated from a methanogenic reactor treating waste from cattle farms. AB - A strictly anaerobic bacterial strain (WK042(T)) was isolated from rice-straw residue in a methanogenic reactor treating waste from cattle farms in Japan. Cells were Gram-staining-negative, non-motile, non-spore-forming rods. Growth was stimulated well by haemin, and was enhanced by cobalamin (vitamin B(12)). Strain WK042(T) utilized arabinose, xylose, glucose, mannose and aesculin as preferred substrates. Maltose, dextrin, glycogen, starch and pectin were also utilized, although growth on these substrates was much slower. The strain produced acetate, propionate and succinate from these saccharides. The strain was slightly alkaliphilic, with optimum growth at pH 7.7. The temperature range for growth was 10-40 degrees C, the optimum being 35 degrees C. The strain was sensitive to bile. The major cellular fatty acids were anteiso-C(15 : 0), iso-C(17 : 0) 3-OH and C(15 : 0). Menaquinone 11 (MK-11) was the major respiratory quinone and the genomic DNA G+C content was 41.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences placed the strain in the phylum Bacteroidetes. Strain WK042(T) was related distantly to the type strains of species in the cluster including Bacteroides massiliensis, Bacteroides vulgatus and Bacteroides dorei (91-92 % 16S rRNA gene sequence similarity). Based on data from the present phylogenetic, physiological and chemotaxonomic analyses, strain WK042(T) is considered to represent a novel species of the genus Bacteroides, for which the name Bacteroides paurosaccharolyticus sp. nov. is proposed. The type strain is WK042(T) (=JCM 15092(T) =DSM 21004(T)). PMID- 20348320 TI - Lysobacter xinjiangensis sp. nov., a moderately thermotolerant and alkalitolerant bacterium isolated from a gamma-irradiated sand soil sample. AB - A yellow-pigmented bacterial strain, designated RCML-52(T), was isolated from an abandoned gold mine in the desert in Xinjiang, China. Strain RCML-52(T) was Gram negative, aerobic and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain RCML-52(T) was affiliated with the genus Lysobacter. Strain RCML-52(T) exhibited <95.6 % 16S rRNA gene sequence similarity to the type strains of all species of the genus Lysobacter. The major fatty acids were iso C(16 : 0) (27.6 %), iso-C(15 : 0) (19.1 %), iso-C(17 : 1)omega9c (16.4 %), iso C(11 : 0) 3-OH (6.5 %) and iso-C(11 : 0) (5.3 %). The DNA G+C content was 69.7 mol%. The major isoprenoid quinone was Q-8. On the basis of phylogenetic, phenotypic and chemotaxonomic analysis, strain RCML-52(T) should be assigned to a novel species of the genus Lysobacter, for which the name Lysobacter xinjiangensis sp. nov. is proposed. The type strain is RCML-52(T) (=CCTCC AB 208194(T) =KCTC 22558(T)). PMID- 20348321 TI - Kordiimonas lacus sp. nov., isolated from a ballast water tank, and emended description of the genus Kordiimonas. AB - A Gram-negative, motile, rod-shaped bacterial strain, designated S3-22(T), was isolated from a sediment sample collected from a ballast water tank of a commercial ship and subjected to a polyphasic taxonomic characterization. The isolate formed small, light-yellow, semi-translucent and circular colonies on solid complex media. The strain was oxidase- and catalase-positive and metabolized a large number of carbon sources. Chemotaxonomic analysis showed ubiquinone Q-10 as predominant respiratory quinone, phosphatidylglycerol and an unidentified glycolipid as major polar lipids and iso-C(17 : 1)omega9c, iso-C(15 : 0), C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH, C(16 : 0), iso-C(17 : 0) and C(18 : 1)omega7c as major fatty acids and the hydroxy fatty acids iso-C(17 : 0) 3 OH and C(16 : 0) 3-OH. The genomic DNA G+C content was 54.9 mol%. 16S rRNA gene sequence analysis revealed that the isolate has 96.1 % similarity to the type strain of Kordiimonas gwangyangensis, the sole described species within the order Kordiimonadales, and less than 91.0 % similarity to other recognized species. On the basis of phenotypic and genotypic data, strain S3-22(T) represents a novel species of the genus Kordiimonas, for which the name Kordiimonas lacus sp. nov. is proposed, with the type strain S3-22(T) (=CGMCC 1.9109(T) =JCM 16261(T)). An emended description of the genus Kordiimonas is also presented. PMID- 20348322 TI - Cocleimonas flava gen. nov., sp. nov., a gammaproteobacterium isolated from sand snail (Umbonium costatum). AB - A Gram-stain-negative, aerobic, yellow-pigmented, heterotrophic, sulfur oxidizing, non-motile, rod-shaped bacterium, designated KMM 3898(T), was isolated from an internal tissue of the sand snail Umbonium costatum, collected from the shallow sediments of the Sea of Japan. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain KMM 3898(T) formed a distinct phylogenetic lineage within the class Gammaproteobacteria and was most closely related to Leucothrix mucor DSM 2157(T) (89.2 % 16S rRNA gene sequence similarity) and members of the genus Thiothrix (86.7-88.5 %). Chemotaxonomically, strain KMM 3898(T) contained the isoprenoid quinone Q-8, the polar lipids phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unknown phospholipid and the fatty acids C(18 : 1)omega7c, C(16 : 1)omega7c and C(16 : 0) as predominant components (>10 %). The DNA G+C content of strain KMM 3898(T) was 43.4 mol%. On the basis of phenotypic features and phylogenetic analysis, strain KMM 3898(T) represents a novel genus and species, for which the name Cocleimonas flava gen. nov., sp. nov. is proposed. The type strain is KMM 3898(T) (=NRIC 0757(T) =JCM 16494(T)). PMID- 20348323 TI - Aquimarina spongiae sp. nov., isolated from marine sponge Halichondria oshoro. AB - A Gram-stain-negative, yellow-pigmented, rod-shaped, strictly aerobic, non flagellated, non-gliding and oxidase- and catalase-positive bacterium, designated A6(T), was isolated from a marine sponge, Halichondria oshoro, collected on the coast of Jeju Island, South Korea. Phylogenetic analysis based on the nearly complete 16S rRNA gene sequence revealed that strain A6(T) was a member of the family Flavobacteriaceae. The closest relatives were Aquimarina intermedia LMG 23204(T), A. latercula ATCC 23177(T), A. brevivitae SMK-19(T) and A. muelleri KMM 6020(T), with which strain A6(T) shared 95.7, 95.1, 94.7 and 94.6 % 16S rRNA gene sequence similarity, respectively. The dominant fatty acids of strain A6(T) were iso-C(15 : 0) (32.2 %), iso-C(17 : 0) 3-OH (20.0 %), iso-C(15 : 0) 3-OH (12.3 %), iso-C(15 : 1) G (7.2 %) and summed feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c; 6.8 %). The DNA G+C content of strain A6(T) was 36.0 mol% and the major respiratory quinone was MK-6. On the basis of combined phenotypic and phylogenetic analyses, strain A6(T) represents a novel species of the genus Aquimarina, for which the name Aquimarina spongiae sp. nov. is proposed. The type strain is A6(T) (=KCTC 22663(T) =DSM 22623(T)). PMID- 20348324 TI - Roseovarius marinus sp. nov., isolated from seawater. AB - A Gram-stain-negative, non-motile, ovoid- to rod-shaped bacterium, designated HDW 9(T), belonging to the class Alphaproteobacteria, was isolated from seawater of the Yellow Sea, Korea. Strain HDW-9(T) grew optimally at pH 7.0-8.0, at 30 degrees C and with 2-3 % (w/v) NaCl. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences showed that strain HDW-9(T) clustered with Roseovarius crassostreae CV919-312(T), with which it exhibited 95.5 % 16S rRNA gene sequence similarity. Strain HDW-9(T) exhibited 92.5-94.7 % 16S rRNA gene sequence similarity with the other type strains of species of the genus Roseovarius. Strain HDW-9(T) contained Q-10 as the predominant ubiquinone and C(18 : 1)omega7c as the major fatty acid. The DNA G+C content was 58.3 mol%. Differential phenotypic properties distinguished strain HDW-9(T) from the other members of the genus Roseovarius. Strain HDW-9(T) is considered to represent a novel species of the genus Roseovarius, for which the name Roseovarius marinus sp. nov. is proposed. The type strain is HDW-9(T) (=KCTC 22805(T) =CCUG 58403(T)). PMID- 20348325 TI - Hydrocarboniphaga daqingensis sp. nov., isolated from a freshwater lake. AB - A Gram-negative bacterium, designated B2-9(T), was isolated from water of a slightly alkaline lake, Longhu Lake in Daqing, north-east China. Strain B2-9(T) was an aerobic rod, heterotrophic, catalase- and oxidase-positive and motile by means of a single polar flflagellum. The isolate grew well on n-alkanes C(9) C(17) and weakly on C(6)-C(8), C(18) and C(19). Growth occurred at 10-37 degrees C (optimum 20-25 degrees C), at pH 5.5-9.5 (optimum pH 7.0) and with <=1.0 % (w/v) NaCl. The major fatty acids were C(18 : 1)omega7c (41.4 %), summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c; 18.5 %) and C(16 : 0) (10.9 %). Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain B2 9(T) belonged to the genus Hydrocarboniphaga of the class Gammaproteobacteria and shared 97.0 % 16S rRNA gene sequence similarity with Hydrocarboniphaga effusa AP103(T). DNA-DNA relatedness between strain B2-9(T) and H. effusa DSM 16095(T) was 24 %. The DNA G+C content of strain B2-9(T) was 66 mol%. Strain B2-9(T) is considered to represent a novel species of the genus Hydrocarboniphaga, for which the name Hydrocarboniphaga daqingensis sp. nov. is proposed. The type strain is B2-9(T) (=CGMCC 1.7049(T) =NBRC 104238(T)). PMID- 20348326 TI - Limnobacter litoralis sp. nov., a thiosulfate-oxidizing, heterotrophic bacterium isolated from a volcanic deposit, and emended description of the genus Limnobacter. AB - A Gram-negative, aerobic, heterotrophic bacterium, designated KP1-19(T), was isolated from a 22-year-old volcanic deposit at a site lacking vegetation on the island of Miyake, Japan. Strain KP1-19(T) was able to use thiosulfate (optimum concentration 10 mM) as an additional energy source. 16S rRNA gene sequence analysis indicated that strain KP1-19(T) was closely related to Limnobacter thiooxidans CS-K2(T) within the class Betaproteobacteria (97.7 % 16S rRNA gene sequence similarity). The cellular fatty acid profile was characteristic of the genus Limnobacter: the major fatty acids (>5 %) were C(16 : 0), C(16 : 1)omega7c and C(18 : 1)omega7c and minor amounts of C(10 : 0) 3-OH were also found. DNA-DNA relatedness between strain KP1-19(T) and L. thiooxidans LMG 19593(T) was 18 %. Therefore, strain KP1-19(T) represents a novel species, for which the name Limnobacter litoralis sp. nov. is proposed. The type strain is KP1-19(T) (=LMG 24869(T) =NBRC 105857(T) =CIP 109929(T)). PMID- 20348327 TI - Communicating evidence and uncertainties on health risks from regular use of mobile phones. PMID- 20348328 TI - Asian economic crises and health: population health impacts and policy responses. PMID- 20348330 TI - Research agenda for environmental reproductive health in the 21st century. PMID- 20348331 TI - Clinical and genetic correlates of circulating angiopoietin-2 and soluble Tie-2 in the community. AB - BACKGROUND: Experimental studies suggest that endothelial growth factors play an important role in angiogenesis and vascular remodeling. The clinical and genetic correlates of circulating angiopoietin-2 (Ang-2) and its soluble receptor/regulator Tie-2 (sTie-2) have not been determined in a community-based sample. METHODS AND RESULTS: Serum Ang-2 and sTie-2 were assayed in 3778 third generation cohort participants of the Framingham Heart Study (mean age, 40+/-9 years; 53% women). Clinical correlates and heritability of both biomarkers were assessed using generalized estimating equations and variance-component analyses. Ang-2 levels were higher and sTie-2 levels were lower in women than in men. Ang-2 was positively related to age, smoking, systolic blood pressure, hypertension treatment, and diabetes (P<0.05 for all) but was inversely associated with total cholesterol and diastolic blood pressure (P<0.0001 for both), and sTie-2 was positively associated with body mass index, diabetes, and triglycerides but was inversely related to age, alcohol consumption, and glomerular filtration rate (P<0.05 for all). Both Ang-2 and sTie-2 were higher in participants with metabolic syndrome (P<0.005), with stronger associations of Ang-2 with blood pressure traits and of sTie-2 with obesity-dyslipidemia components. Heritability estimates for Ang-2 and sTie-2 were 27% and 56%, respectively (P<0.0001). A region on chromosome 9 was significantly linked to circulating sTie-2 levels (logarithm of the odds score, 8.31). CONCLUSION: Circulating levels of Ang-2 and sTie-2 are heritable traits associated with cardiovascular disease risk factors, including the metabolic syndrome. These observations are consistent with the notion that angiogenesis and vascular remodeling are determined in part by genetic influences and associated with metabolic risk factors. PMID- 20348332 TI - A wake-based correlate of swimming performance and foraging behavior in seven co occurring jellyfish species. AB - It is generally accepted that animal-fluid interactions have shaped the evolution of animals that swim and fly. However, the functional ecological advantages associated with those adaptations are currently difficult to predict on the basis of measurements of the animal-fluid interactions. We report the identification of a robust, fluid dynamic correlate of distinct ecological functions in seven jellyfish species that represent a broad range of morphologies and foraging modes. Since the comparative study is based on properties of the vortex wake- specifically, a fluid dynamical concept called optimal vortex formation--and not on details of animal morphology or phylogeny, we propose that higher organisms can also be understood in terms of these fluid dynamic organizing principles. This enables a quantitative, physically based understanding of how alterations in the fluid dynamics of aquatic and aerial animals throughout their evolution can result in distinct ecological functions. PMID- 20348333 TI - High-precision tracking of sperm swimming fine structure provides strong test of resistive force theory. AB - The shape of the flagellar beat determines the path along which a sperm cell swims. If the flagellum bends periodically about a curved mean shape then the sperm will follow a path with non-zero curvature. To test a simple hydrodynamic theory of flagellar propulsion known as resistive force theory, we conducted high precision measurements of the head and flagellum motions during circular swimming of bull spermatozoa near a surface. We found that the fine structure of sperm swimming represented by the rapid wiggling of the sperm head around an averaged path is, to high accuracy, accounted for by resistive force theory and results from balancing forces and torques generated by the beating flagellum. We determined the anisotropy ratio between the normal and tangential hydrodynamic friction coefficients of the flagellum to be 1.81+/-0.07 (mean+/-s.d.). On time scales longer than the flagellar beat cycle, sperm cells followed circular paths of non-zero curvature. Our data show that path curvature is approximately equal to twice the average curvature of the flagellum, consistent with quantitative predictions of resistive force theory. Hence, this theory accurately predicts the complex trajectories of sperm cells from the detailed shape of their flagellar beat across different time scales. PMID- 20348334 TI - Deployment of hagfish slime thread skeins requires the transmission of mixing forces via mucin strands. AB - Hagfishes are benthic marine protovertebrates that secrete copious quantities of slime when threatened. The slime originates as a two-component glandular exudate comprised of coiled bundles of cytoskeletal intermediate filaments (thread skeins) and mucin vesicles. Holocrine secretion of the slime into seawater results in the rapid deployment of both fibrous and mucin components, resulting in about a liter of dilute slime. Deployment of the thread skeins involves their unraveling in a fraction of a second from a 150 microm-long ellipsoid bundle to a thread that is 100x longer. We hypothesized that thread skein deployment requires both vigorous hydrodynamic mixing and the presence of mucin vesicles, both of which are required for whole slime deployment. Here we provide evidence that mixing and mucin vesicles are indeed crucial for skein unraveling. Specifically, we show that mucin vesicles mixed into seawater swell and elongate into high aspect ratio mucin strands that attach to the thread skeins, transmit hydrodynamic forces to them and effect their unraveling by loading them in tension. Our discovery of mucin strands in hagfish slime not only provides a mechanism for the rapid deployment of thread skeins in vivo, it also helps explain how hagfish slime is able to trap such impressive volumes of seawater via viscous entrainment. We believe that the deployment of thread skeins via their interaction with shear-elongated mucins represents a unique mechanism in biology and may lead to novel technologies for transmitting hydrodynamic forces to microscale particles that would typically be immune to such forces. PMID- 20348335 TI - It's tough to be small: dependence of burrowing kinematics on body size. AB - Burrowing marine infauna are morphologically diverse and range in size over several orders of magnitude. Whilst effects of ontogenetic and morphological differences on running, flying and swimming are relatively well understood, similar analyses of burrowing mechanics and kinematics are lacking. The polychaete Nereis virens Sars extends its burrow by fracture, using an eversible pharynx to exert force on the walls of the burrow. The resulting stress is amplified at the anterior tip of the burrow, which extends when the stress exceeds the fracture toughness of the material. Here we show that the polychaete Cirriformia moorei extends its burrow by a similar mechanism, but by using its hydrostatic skeleton rather than an eversible pharynx. Based on the dimensionless wedge number, which relates work of fracture to work to maintain body shape against the elasticity of sediment, we predicted that smaller worms would exhibit behaviors characteristic of tougher sediments and that scaling of kinematics would reflect decreasing difficulty in fracturing sediment with increasing body size. We found that smaller worms were relatively blunter and thicker, and had a greater variation of thickness than larger worms as they burrowed. Although these kinematic differences increase the stress amplification at the crack tip, smaller worms still generate lower stress intensity factors. The greater relative body thickness and shape changes of smaller worms are consistent with ontogenetic changes in forces exerted by earthworms, and are likely driven by the challenge of exerting enough stress to extend a crack with a small body size. PMID- 20348336 TI - Gamma-amino butyric acid (GABA) release in the ciliated protozoon Paramecium occurs by neuronal-like exocytosis. AB - Paramecium primaurelia expresses a significant amount of gamma-amino butyric acid (GABA). Paramecia possess both glutamate decarboxylase (GAD)-like and vesicular GABA transporter (vGAT)-like proteins, indicating the ability to synthesize GABA from glutamate and to transport GABA into vesicles. Using antibodies raised against mammalian GAD and vGAT, bands with an apparent molecular weight of about 67 kDa and 57 kDa were detected. The presence of these bands indicated a similarity between the proteins in Paramecium and in mammals. VAMP, syntaxin and SNAP, putative proteins of the release machinery that form the so-called SNARE complex, are present in Paramecium. Most VAMP, syntaxin and SNAP fluorescence is localized in spots that vary in size and density and are primarily distributed near the plasma membrane. Antibodies raised against mammal VAMP-3, sintaxin-1 or SNAP-25 revealed protein immunoblot bands having molecular weights consistent with those observed in mammals. Moreover, P. primaurelia spontaneously releases GABA into the environment, and this neurotransmitter release significantly increases after membrane depolarization. The depolarization-induced GABA release was strongly reduced not only in the absence of extracellular Ca(2+) but also by pre-incubation with bafilomycin A1 or with botulinum toxin C1 serotype. It can be concluded that GABA occurs in Paramecium, where it is probably stored in vesicles capable of fusion with the cell membrane; accordingly, GABA can be released from Paramecium by stimulus-induced, neuronal-like exocytotic mechanisms. PMID- 20348337 TI - In vivo mechanical response of human Achilles tendon to a single bout of hopping exercise. AB - Stiffness of the human Achilles tendon (AT) was determined in vivo before and after a single bout of hopping exercise. It was hypothesized, based on published data using in vitro specimens, that a reduction in AT stiffness may occur after just 1000 loading cycles at physiological stress levels. Ten healthy subjects performed two-legged hopping exercise consisting of 1150-2600 high impacts. Tendon stiffness was determined in several isometric ramp contractions [20%, 40%, 60%, 80% and 100% maximum voluntary contraction (MVC)] during which tendon elongation was measured using ultrasonography and two cameras. Tendon force was calculated by dividing measured ankle torque by magnetic resonance imaging derived AT lever arm length. Tendon stiffness remained unchanged, being 430+/-200 N mm(-1) before and 390+/-190 N mm(-1) after the exercise [not significant (n.s.)]. Despite the lack of changes in stiffness, maximum tendon force during MVC was reduced from 3.5+/-0.6 kN to 2.8+/-0.7 kN (P<0.01). As the proposed decline in stiffness was not observed, it is concluded that mechanical fatigue did not take place in the AT of healthy individuals after a single bout of high impact exercise performed until exhaustion. PMID- 20348338 TI - Fuel switching and energy partitioning during the postprandial metabolic response in the ball python (Python regius). AB - Digestion, absorption and assimilation of the meal are active processes that require start-up energy before the energy contained in a meal can be utilized. The energetic costs associated with feeding (specific dynamic action, SDA) are high in sit-and-wait foraging snakes that tolerate long fasting periods. We used (13)C-labelled prey to partition between endogenous energy sources (i.e. snakes' own resources) and exogenous energy sources (i.e. prey). A linear mixing model was then applied to determine the portion of (13)C originating from the different sources. The snakes showed a normal and typical postprandial response. By four hours after feeding, the delta(13)C-values indicated fuel switching from endogenous to exogenous. From then on, fuel mixing continuously increased until, at 20 h after feeding, 75% of fuel was exogenous. Resource partitioning showed that throughout SDA, the amount of exogenous energy increased to approximately 60% of SDA, which was equivalent to approximately 4.5% of the energy contained in a meal. PMID- 20348339 TI - Male moths bearing transplanted female antennae express characteristically female behaviour and central neural activity. AB - The primary olfactory centres of the sphinx moth Manduca sexta, the antennal lobes, contain a small number of sexually dimorphic glomeruli: the male-specific macroglomerular complex and the large female glomeruli. These glomeruli play important roles in sex-specific behaviours, such as the location of conspecific females and the selection of appropriate host plants for oviposition. The development of sexually dimorphic glomeruli depends strictly on the ingrowth of sex-specific olfactory receptor cell afferents. In the present study we tested the role of female-specific olfactory receptor cells (ORCs) in mediating female specific host plant approach behaviour and in determining the response of downstream antennal lobe neurons. We generated male gynandromorphs by excising one imaginal disc from a male larva and replacing it with the antennal imaginal disc from a female donor. Most male gynandromorphs had an apparently normal female antenna and a feminised antennal lobe. These gynandromorphs were tested for flight responses in a wind tunnel towards tomato plants, a preferred host plant for oviposition in M. sexta. Male gynandromorphs landed on host plants as often as normal females, demonstrating that the presence of the induced female specific glomeruli was necessary and sufficient to produce female-like, odour oriented behaviour, i.e. orientation towards host plants. We also characterised the physiological and morphological properties of antennal lobe neurons of male gynandromorphs. We found that projection neurons with arborisations in the induced female-specific glomeruli showed physiological responses akin to those of female-specific projection neurons in normal females. These results therefore indicate that ORCs confer specific odour tuning to their glomerular targets and, furthermore, instruct odour-specific behaviour. PMID- 20348340 TI - Morphology-flow interactions lead to stage-selective vertical transport of larval sand dollars in shear flow. AB - Many larvae and other plankton have complex and variable morphologies of unknown functional significance. We experimentally and theoretically investigated the functional consequences of the complex morphologies of larval sand dollars, Dendraster excentricus (Eschscholtz), for hydrodynamic interactions between swimming and turbulent water motion. Vertical shearing flows (horizontal gradients of vertical flow) tilt organisms with simple geometries (e.g. spheres, ellipsoids), causing these organisms to move horizontally towards downwelling water and compromising their abilities to swim upwards. A biomechanical model of corresponding hydrodynamic interactions between turbulence-induced shear and the morphologically complex four-, six- and eight-armed stages of sand dollar larvae suggests that the movements of larval morphologies differ quantitatively and qualitatively across stages and shear intensities: at shear levels typical of calm conditions in estuarine and coastal environments, all modeled larval stages moved upward. However, at higher shears, modeled four- and eight-armed larvae moved towards downwelling, whereas six-armed larvae moved towards upwelling. We also experimentally quantified larval movement by tracking larvae swimming in low intensity shear while simultaneously mapping the surrounding flow fields. Four- and eight-armed larvae moved into downwelling water, but six-armed larvae did not. Both the model and experiments suggest that stage-dependent changes to larval morphology lead to differences in larval movement: four- and eight-armed stages are more prone than the six-armed stage to moving into downwelling water. Our results suggest a mechanism by which differences can arise in the vertical distribution among larval stages. The ability to mitigate or exploit hydrodynamic interactions with shear is a functional consequence that potentially shapes larval evolution and development. PMID- 20348341 TI - Life in acid: interactive effects of pH and natural organic acids on growth, development and locomotor performance of larval striped marsh frogs (Limnodynastes peronii). AB - The low pH of naturally acidic aquatic environments is the result of soft-water with low buffering capacity and high concentrations of natural organic acids. Our current understanding of the influence of pH on aquatic organisms is largely limited to laboratory studies conducted under controlled conditions with little incorporation of these organic acids. Recent studies suggest natural organic acids may influence the physiology of aquatic species independent of low pH. We examined the effects of pH and varying concentrations of natural wallum water, which is high in organic acids on the hatching success, growth and locomotor performance of larval striped marsh frogs (Limnodynastes peronii). Based on previous studies, we predicted that the detrimental effects of low pH would be further exacerbated by higher concentrations of naturally occurring organic acids (high concentrations of wallum water). In artificial soft-water, embryos experienced both reduced growth and reduced survival when exposed to low pH. However, greater concentrations of natural organic acids did not exacerbate these effects of low pH on growth and development. Instead, we found some evidence that the natural organic acids within wallum water improved growth and swimming performance across all pH treatments. Using path analyses to investigate the effects of pH and natural organic acid concentration on burst swimming performance, we found performance was directly affected by both body length and organic acid concentration. Our data further highlight our limited understanding of the importance of natural organic acids for aquatic organisms and the need to incorporate greater ecological relevance into these studies. PMID- 20348342 TI - Activity, abundance, distribution and expression of Na+/K+-ATPase in the salt glands of Crocodylus porosus following chronic saltwater acclimation. AB - Saltwater crocodiles, Crocodylus porosus, possess lingual salt glands which function to remove excess Na(+) and Cl(-) accumulated as a consequence of living in salt water. Little is known about the nature of ion transport systems in C. porosus salt glands and how these systems respond to an osmotic challenge. In the present study, we examined the distribution and regulation of the Na(+)/K(+) ATPase (NKA) pump, specifically the alpha-(catalytic) subunit in the salt glands of C. porosus chronically acclimated (6 months) to freshwater (FW) or 70% seawater (SW). We hypothesised that in the SW-acclimated C. porosus there would be an up-regulation of the abundance, activity and gene expression of the NKA transporter. NKA was immunolocalised to the lateral and basal membrane of secretory cells. As predicted, the NKA alpha-subunit was 2-fold more abundant in SW-acclimated C. porosus salt glands. NKA gene expression was also elevated in the salt glands of SW- vs FW-acclimated crocodiles. There was no increase in the specific activity of NKA in SW-acclimated animals and the in vitro rate of oxygen consumption by salt gland slices from SW-acclimated animals was not significantly different from that of FW-acclimated animals. The proportion of tissue oxygen consumption rate attributable to NKA activity was not different between SW- and FW-acclimated animals (approximately 50%). These data suggest that either chronic SW acclimation does not affect NKA in crocodile salt glands in the same manner as seen in other models or crocodiles possess the capacity to moderate NKA activity following prolonged exposure to SW. PMID- 20348343 TI - Hydrodynamic sensing does not facilitate active drag reduction in the golden shiner (Notemigonus crysoleucas). AB - The lateral line system detects water flow, which allows fish to orient their swimming with respect to hydrodynamic cues. However, it is unclear whether this sense plays a role in the control of propulsion. Hydrodynamic theory suggests that fish could reduce drag by coordinating the motion of the head relative to detected flow signals. To test this hypothesis, we performed measurements of undulatory kinematics during steady swimming in the golden shiner (Notemigonus crysoleucas) at three speeds (4.5, 11.0 and 22.0 cm s(-1)). We found that the phase shift between yaw angle and lateral velocity (20.5+/-13.1 deg., N=5) was significantly greater than the theoretical optimum (0 deg.) and the amplitude of these variables created a hydrodynamic index (H=0.05+/-0.03, N=6) that was less than an order of magnitude below the theoretical prediction. Furthermore, we repeated these measurements after pharmacologically ablating the lateral line hair cells and found that drag reduction was not adversely influenced by disabling the lateral line system. Therefore, flow sensing does not facilitate active drag reduction. However, we discovered that ablating the lateral line causes the envelope of lateral displacement to nearly double at the envelope's most narrow point for swimming at 4.5 cm s(-1). Therefore, fish may use hydrodynamic sensing to modulate the lateral amplitude of slow undulatory swimming, which could allow rapid responses to changes in environmental flow. PMID- 20348344 TI - Hindlimb interarticular coordinations in Microcebus murinus in maximal leaping. AB - The purpose of this study was to investigate the pattern of coordinations of the hindlimb joints in the world's smallest living primate (Microcebus murinus). The sequencing and timing of joint rotations have been analyzed in five adult males performing maximal leaping from a take-off immobile platform to their own wooden nest. Angular kinematics of hip, knee, angle and metatarso-phalangeal (MT) joints were deduced from high-speed X-ray films in the sagittal plane of the animals. The body mass center (BMC) of the lemurs was assimilated to their iliac crest. The maximal airborne performance of the lemurs was 0.33+/-0.04 m, which represented 2.55+/-0.36 times their snout-vent length. Take-off instant occurred 72+/-7 ms after the start of the push-off, with a BMC velocity of 3.23+/-0.48 m s(-1), oriented 55+/-14 deg. with the horizontal plane. The kinematic analysis of the joints and musculo-tendon architecture of the M. murinus plantar flexors pointed out mechanical power amplifier mechanisms (i.e. stretch-shortening cycle of hindlimb muscles and proximo-to-distal sequence). PMID- 20348345 TI - When surfacers do not dive: multiple significance of extended surface times in marine turtles. AB - Marine turtles spend more than 90% of their life underwater and have been termed surfacers as opposed to divers. Nonetheless turtles have been reported occasionally to float motionless at the surface but the reasons for this behaviour are not clear. We investigated the location, timing and duration of extended surface times (ESTs) in 10 free-ranging loggerhead turtles (Caretta caretta) and the possible relationship to water temperature and diving activity recorded via satellite relay data loggers for 101-450 days. For one turtle that dived only in offshore areas, ESTs contributed 12% of the time whereas for the other turtles ESTs contributed 0.4-1.8% of the time. ESTs lasted on average 90 min but were mostly infrequent and irregular, excluding the involvement of a fundamental regulatory function. However, 82% of the ESTs occurred during daylight, mostly around noon, suggesting a dependence on solar radiation. For three turtles, there was an appreciable (7 degrees C to 10.5 degrees C) temperature decrease with depth for dives during periods when ESTs occurred frequently, suggesting a re-warming function of EST to compensate for decreased body temperatures, possibly to enhance digestive efficiency. A positive correlation between body mass and EST duration supported this explanation. By contrast, night-active turtles that exceeded their calculated aerobic dive limits in 7.6-16% of the dives engaged in nocturnal ESTs, probably for lactate clearance. This is the first evidence that loggerhead turtles may refrain from diving for at least two reasons, either to absorb solar radiation or to recover from anaerobic activity. PMID- 20348346 TI - Short-term group fission processes in macaques: a social networking approach. AB - Living in groups necessarily involves a certain amount of within-group competition for food. Group members may have different motivations, implying the reaching of a consensus to stay cohesive. In some cases individuals fail to reach a common decision and the group splits; this can be temporary, as seen in fission fusion dynamics, or even irreversible. Most studies on fission-fusion dynamics published to date have focused on the influence of environmental constraints on sub-grouping patterns, but little is known about how social relationships affect individual choices for sub-groups. In this study, we used an agent-based model to understand the mechanisms underlying group fission in two semi-free-ranging groups of macaques: one group of Tonkean macaques (Macaca tonkeana) and one of rhesus macaques (M. mulatta). The results showed that sub-grouping patterns were mainly influenced by affiliative relationships. Moreover, the species-specific social style appeared to affect the probability of choosing a particular sub group. In the tolerant Tonkean macaques, mechanisms underlying sub-grouping patterns resembled anonymous mimetism, while in the nepotistic rhesus macaques, kinship influenced the mechanisms underlying group fissions. As previous studies have shown, fission-fusion society may be a way to avoid social conflicts induced either by food or by social competition. PMID- 20348347 TI - Ontogenetic scaling of locomotor kinetics and kinematics of the ostrich (Struthio camelus). AB - Kinematic and kinetic parameters of running gait were investigated through growth in the ostrich, from two weeks up to 10 months of age, in order to investigate the effects of increasing body size. Ontogenetic scaling relationships were compared with published scaling relationships found to exist with increasing body size between species to determine whether dynamic similarity is maintained during growth. During the study, ostrich mass (M(b)) ranged from 0.7 kg to 108.8 kg. Morphological measurements showed that lengths scaled with positive allometry during growth (hip height proportional to M(b)(0.40); foot segment length proportional to M(b)(0.40); tarsometatarsus length proportional to M(b)(0.41); tibiotarsus length proportional to M(b)(0.38); femur length proportional to M(b)(0.37)), significantly exceeding the close to geometric scaling observed between mammalian and avian species of increasing body size. Scaling of kinematic variables largely agreed with predicted scaling for increasing size and demonstrated relationships close to dynamic similarity and, as such, ontogenetic scaling of locomotor parameters was similar to that observed with increasing body mass between species. However, the ways in which these scaling trends were achieved were very different, with ontogenetic scaling of locomotor mechanics largely resulting from simple scaling of the limb segments rather than postural changes, likely to be due to developmental constraints. Small deviations from dynamic similarity of kinematic parameters and a reduction in the predicted scaling of limb stiffness (proportional to M(b)(0.59)) were found to be accounted for by the positive allometric scaling of the limb during growth. PMID- 20348348 TI - Behavioral choice across leech species: chacun a son gout. AB - At any one time, animals are simultaneously bombarded with many sensory stimuli, but they typically choose to respond to only a few of them. We used multidimensional analysis to determine the behavioral responses of six species of leeches to stimulation, as the responses are affected by species identity, diet, behavioral state and stimulus location. Our results show that each of the species tested while not feeding displayed remarkably similar behaviors in response to tactile stimulation of the surface of the body. When not feeding, stimulus location was the most reliable factor in determining behavioral response. While feeding, the three sanguivorous (bloodsucking) species tested ignored stimulation, whereas the three carnivorous leeches abandoned feeding in favor of locomotory responses, regardless of phylogenetic relationships. In the sanguivorous leeches, feeding abolished all mechanically elicited responses and mechanical stimulation in turn had no effect on feeding. We also show that the behavioral hierarchy of leeches was fixed and unchanging even in species that can consume both a carnivorous and a sanguivorous diet. PMID- 20348349 TI - Dynamics of optomotor responses in Drosophila to perturbations in optic flow. AB - For a small flying insect, correcting unplanned course perturbations is essential for navigating through the world. Visual course control relies on estimating optic flow patterns which, in flies, are encoded by interneurons of the third optic ganglion. However, the rules that translate optic flow into flight motor commands remain poorly understood. Here, we measured the temporal dynamics of optomotor responses in tethered flies to optic flow fields about three cardinal axes. For each condition, we used white noise analysis to determine the optimal linear filters linking optic flow to the sum and difference of left and right wing beat amplitudes. The estimated filters indicate that flies react very quickly to perturbations of the motion field, with pure delays in the order of approximately 20 ms and time-to-peak of approximately 100 ms. By convolution the filters also predict responses to arbitrary stimulus sequences, accounting for over half the variance in 5 of our 6 stimulus types, demonstrating the approximate linearity of the system with respect to optic flow variables. In the remaining case of yaw optic flow we improved predictability by measuring individual flies, which also allowed us to analyze the variability of optomotor responses within a population. Finally, the linear filters at least partly explain the optomotor responses to superimposed and decomposed compound flow fields. PMID- 20348350 TI - Neural responses to one- and two-tone stimuli in the hearing organ of the dengue vector mosquito. AB - Recent studies demonstrate that mosquitoes listen to each other's wing beats just prior to mating in flight. Field potentials from sound-transducing neurons in the antennae contain both sustained and oscillatory components to pure and paired tone stimuli. Described here is a direct comparison of these two types of response in the dengue vector mosquito, Aedes aegypti. Across a wide range of frequencies and intensities, sustained responses to one- and two-tone stimuli are about equal in magnitude to oscillatory responses to the beats produced by two tone stimuli. All of these responses are much larger than the oscillatory responses to one-tone stimuli. Similarly, the frequency range extends up to at least the fifth harmonic of the male flight tone for sustained responses to one- and two-tone stimuli and oscillatory responses at the beat frequency of two-tone stimuli, whereas the range of oscillatory response to a one-tone stimulus is limited to, at most, the third harmonic. Thresholds near the fundamental of the flight tone are lower for oscillatory responses than for sustained deflections, lower for males than for females, and within the behaviorally relevant range. A simple model of the transduction process can qualitatively account for both oscillatory and sustained responses to pure and paired tones. These data leave open the question as to which of several alternative strategies underlie flight tone matching behavior in mosquitoes. PMID- 20348351 TI - Is there an energetic-based trade-off between thermoregulation and the acute phase response in zebra finches? AB - There has been recent interest in understanding trade-offs between immune function and other fitness-related traits. At proximate levels, such trade-offs are presumed to result from the differential allocation of limited energy resources. Whether the costs of immunity are sufficient to necessitate such energy reallocation remains unclear. We tested the metabolic and behavioural response of male zebra finches (Taeniopygia guttata) to the combined effects of thermoregulation and generation of an acute phase response (APR). The APR is the first line of defence against pathogens, and is considered energetically costly. We predicted that at cold temperatures zebra finches would exhibit an attenuated APR when compared with individuals at thermoneutrality. We challenged individuals with bacterial lipopolysaccharide (LPS), an immunogenic compound that stimulates an APR. Following LPS injection, we measured changes in food intake, body mass, activity, and resting and total energy expenditure. When challenged with LPS under ad libitum food, individuals at both temperatures decreased food intake and activity, resulting in similar mass loss. In contrast to predicted energetic trade-offs, cold-exposed individuals injected with LPS increased their nocturnal resting energy expenditure more than did individuals held at thermoneutrality, yet paradoxically lost less mass overnight. Although responding to LPS was energetically costly, resulting in a 10% increase in resting expenditure and 16% increase in total expenditure, there were few obvious energetic trade-offs. Our data support recent suggestions that the energetic cost of an immune response may not be the primary mechanism driving trade-offs between immune system function and other fitness-related traits. PMID- 20348352 TI - Auxin polar transport is essential for the development of zygote and embryo in Nicotiana tabacum L. and correlated with ABP1 and PM H+-ATPase activities. AB - Auxin is an important plant growth regulator, and plays a key role in apical basal axis formation and embryo differentiation, but the mechanism remains unclear. The level of indole-3-acetic acid (IAA) during zygote and embryo development of Nicotiana tabacum L. is investigated here using the techniques of GC-SIM-MS analysis, immunolocalization, and the GUS activity assay of DR5::GUS transgenic plants. The distribution of ABP1 and PM H(+)-ATPase was also detected by immunolocalization, and this is the first time that integral information has been obtained about their distribution in the zygote and in embryo development. The results showed an increase in IAA content in ovules and the polar distribution of IAA, ABP1, and PM H(+)-ATPase in the zygote and embryo, specifically in the top and basal parts of the embryo proper (EP) during proembryo development. For information about the regulation mechanism of auxin, an auxin transport inhibitor TIBA (2,3,5-triiodobenzoic acid) and exogenous IAA were, respectively, added to the medium for the culture of ovules at the zygote and early proembryo stages. Treatment with a suitable IAA concentration promoted zygote division and embryo differentiation, while TIBA treatment obviously suppressed these processes and caused the formation of abnormal embryos. The distribution patterns of IAA, ABP1, and PM H(+)-ATPase were also disturbed in the abnormal embryos. These results indicate that the polar distribution and transport of IAA begins at the zygote stage, and affects zygote division and embryo differentiation in tobacco. Moreover, ABP1 and PM H(+)-ATPase may play roles in zygote and embryo development and may also be involved in IAA signalling transduction. PMID- 20348353 TI - Why should men and women marry and have children? Parenthood, marital status and self-perceived stress among Canadians. AB - Using the Canadian Community and Health Survey (2000), this study examines self perceived stress across marital and parental statuses, adjusting for age, education, work status, income and sense of community belonging. Results show that fatherhood increases perceived stress regardless of marital status, particularly among singles. Motherhood does not affect perceived stress among married or cohabitating women but single and post-married mothers endure the highest levels of stress. Interactions between working and parental or marital statuses are also observed. Community belonging acts as a coping mechanism in lowering stress levels. Results are discussed in the context of changing familial roles. PMID- 20348354 TI - Age, relative autonomy and change in health locus of control beliefs: a longitudinal study of members of a health-promotion facility. AB - Health locus of control (HLC) describes an individual's characteristic attribution of health outcomes to internal or external causes. This four-year longitudinal study examined changes in HLC beliefs among 124 members of a health promotion facility, related to their age (22-81) and relative autonomy toward health-related goals. HLC beliefs changed with age as developmental theories of control striving would predict. Holding age aside, the pursuit of health goals with more relative autonomy significantly offset the growth of external-chance HLC beliefs. Lack of autonomy thus appears to permit development of fatalistic attributions that may affect later coping with adverse health events. PMID- 20348355 TI - Living with HIV/AIDS and use of online support groups. AB - The present study explores the association between online support group use and health status, coping and social support among 640 individuals with HIV/AIDS. Results suggested that frequent users tended to be female, younger, single, and in a more advanced disease stage. After controlling for covariates, frequent users reported poorer health than non-users. In addition, both frequent and infrequent users scored higher in planning, active coping, instrumental support and emotional support coping from the brief COPE. No significant difference was found for social support. Our results suggest that online support groups may potentially offer some benefits for those living with HIV/AIDS. PMID- 20348356 TI - An investigation of victimization and the clinical course of chronic fatigue syndrome. AB - Medically unexplained syndromes, including chronic fatigue syndrome (CFS), have been associated with victimization in childhood and adulthood. The purpose of this study was to examine the associations of victimization experiences in childhood and adulthood with functional status and illness severity in a sample of patients with CFS using longitudinal data. In the sample of 93 patients with CFS, childhood abuse and neglect had greater impact than adulthood victimization. Overall, victimization experiences in childhood demonstrated modest associations with clinical outcomes in CFS, although several victimization experiences were in the opposite direction of expectations. Victimization predicted worse outcomes, but not worsening outcomes over time. PMID- 20348357 TI - Interdisciplinary physical activity counseling in primary care: a qualitative inquiry of the patient experience. AB - The Physical Activity Counseling randomized controlled trial integrated a physical activity (PA) counselor into a primary care practice to provide intensive counseling to sedentary patients following brief counseling from their regular health care provider. This article presents the voices of 15 patients, who through a series of 3 interviews, described their experience with this 3 month combined provider PA counseling intervention. Patient satisfaction was a dominant emergent theme, and the patients were particularly positive about the quality of care and educational support for lifestyle change. They favored the tailored approach and felt the strategies for overcoming PA barriers were helpful. PMID- 20348358 TI - Validation of the food thought suppression inventory. AB - The Food Thought Suppression Inventory (FTSI) was designed as a domain-specific measure of food-related thought suppression, and the FTSI has been found to be associated with eating pathology, including binge eating. Although initial research in this area is promising, as it may provide understanding of the cognitive processes related to the development of eating pathology and obesity, little is known about the psychometric properties of the FTSI. In the current study, the validity of the FTSI was examined, and the FTSI was found to be a valid, reliable, single factor measure of food thought suppression. PMID- 20348359 TI - Obesity treatment tailored for a Catholic faith community: a feasibility study. AB - Most faith-based obesity intervention research has been conducted in African American Protestant churches. However, Catholic communities might also benefit from a faith-tailored approach. Overweight Catholic individuals (n = 34, 71% female) were randomized to a Catholic-tailored or standard behavioral 16-week group weight control program. Both conditions experienced significant weight losses (Catholic-tailored: -8.1 + 4.1%, Standard: -7.9 + 4.2%); however, treatment satisfaction was significantly greater in the Catholic-tailored program. The Catholic-tailored program experienced trends for greater attendance, more completed self-monitoring journals, and smaller weight regain six months post-treatment than the standard program. Catholic-tailored programs may represent a feasible, culturally acceptable and effective approach to weight loss/maintenance in this faith community. PMID- 20348360 TI - A prospective investigation of interpersonal influences on the pursuit of muscularity in late adolescent boys and girls. AB - This project examined whether interpersonal pressure to be muscular predicted late adolescents' pursuit of muscularity. Participants were 199 adolescents (16 19 years), mothers (n = 175), and friends (n = 159), assessed at two annual times. Pressure to be muscular was assessed with adolescents', mothers', and friends' reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents', mothers', and friends' reports of pressure related to pursuit of muscularity at both times. Adolescents' perceptions and mothers' reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents. PMID- 20348361 TI - The effects of clown intervention on worries and emotional responses in children undergoing surgery. AB - This study investigated whether clown intervention could reduce preoperative worries and the affective responses of children undergoing minor surgery. Parental anxiety was also tested. Child's age, previous hospitalization, and temperament were tested as predictors of the child's responses during this preoperative phase. Seventy children were assigned to one of two groups: children accompanied by their parents and a pair of clowns or, those accompanied by the parents but without the clowns. The results emphasized the relevance of clown intervention on the reduction of preoperative worries and emotional responses, not only in children but also in their parents. PMID- 20348362 TI - Anti-fat, pro-slim, or both? Using two reaction-time based measures to assess implicit attitudes to the slim and overweight. AB - Two measures of implicit attitudes, the Implicit Relational Assessment Procedure (IRAP) and the Implicit Association Test (IAT), were compared with each other and with a measure of explicit attitudes in the assessment of implicit pro-slim/anti fat bias. Results from both implicit tests indicated higher levels of bias than revealed by the explicit measure. The IRAP data suggested that it was participants' pro-slim rather than anti-fat bias, which was driving this effect. Explicit attitudes and feelings towards the overweight were significant predictors of behavioural intentions towards the overweight with the IRAP offering a greater contribution to predictive validity than the IAT. PMID- 20348363 TI - A discourse analytic study of ME/CFS (Chronic Fatigue Syndrome) sufferers' experiences of interactions with doctors. AB - The aetiology, symptoms, diagnosis and treatment of ME/CFS are controversial. Doctors and sufferers often have opposing perspectives, leading to problematic clinical interactions. We use discourse analysis to explore ME/CFS sufferers' descriptions of interactions with medical professionals taken from an asynchronous, online sufferers' support group. Participants described themselves as experiencing limited medical care and attention but restricted criticisms to 'legitimate', pragmatic or ancillary matters such as a clinicians' unwillingness to prescribe untested treatments. Participants also described themselves as active in seeking a resolution to their problems. They thus attended to possible negative attributions of being 'complaining' or unmotivated to seek recovery. PMID- 20348364 TI - Kidney patients' intention to receive a deceased donor transplant: development of stage of change, decisional balance and self-efficacy measures. AB - In order to sustain life, patients whose kidneys fail must receive dialysis or obtain a transplant. This study reports on the development and validation of measures of Stage of Change, Decisional Balance and Self-efficacy based on the Transtheoretical Model (TTM) to assess patients' readiness to receive a deceased donor transplant. We surveyed 293 transplant-eligible kidney patients about their deceased donation readiness. Exploratory and confirmatory analyses for all measures demonstrated factor structures similar to previous application of the TTM to other health behaviors, excellent model fit and good internal and external validity. These brief, reliable instruments with good psychometric properties can guide the development of improved, individually-tailored transplant education for patients. PMID- 20348365 TI - The influence of vaccine-critical websites on perceiving vaccination risks. AB - This large-scale Internet-experiment tests whether vaccine-critical pages raise perceptions of the riskiness of vaccinations and alter vaccination intentions. We manipulated the information environment (vaccine-critical website, control, both) and the focus of search (on vaccination risks, omission risks, no focus). Our analyses reveal that accessing vaccine-critical websites for five to 10 minutes increases the perception of risk of vaccinating and decreases the perception of risk of omitting vaccinations as well as the intentions to vaccinate. In line with the 'risk-as-feelings' approach, the affect elicited by the vaccine-critical websites was positively related to changes in risk perception. PMID- 20348366 TI - 'Feelings of guilt due to self-inflicted disease': a grounded theory of suffering from chronic obstructive pulmonary disease (COPD). AB - The aim of this grounded theory study was to illuminate the main concern of people suffering from chronic obstructive pulmonary disease (COPD) and how they handle their everyday life. Data were collected through interviews with 23 people with COPD at different stages, from mild to severe. A substantive theory was generated showing that the main concern was feelings of guilt due to self inflicted disease associated with smoking habits. This core category was related to five managing strategies termed making sense of existence, adjusting to bodily restrictions, surrendering to fate, making excuses for the smoking-related cause and creating compliance with daily medication. PMID- 20348367 TI - Motives and health-related behaviours: an investigation of equipotentiality and equifinality. AB - We investigated the phenomena of equipotentiality (one dispositional motive expressed through more than one behaviour) and equifinality (one behaviour serving more than one motive). In a cross-sectional survey, 244 young adults completed measures of sun-related behaviour and risky sexual behaviour, participatory motives for the behaviours and life goals (representing dispositional motives). Equipotentiality was demonstrated, in that power and diversity life goals each predicted more than one behaviour. Equifinality was demonstrated, in that sun exposure and risky sexual behaviour were each predicted by more than one life goal. Participatory motives mediated these relationships. Equipotentiality and equifinality need to be taken into account in health promotion. PMID- 20348368 TI - Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. AB - OBJECTIVE: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has anticolorectal cancer activity in vitro and in preclinical models. The present study tested whether a novel, enteric-coated formulation of EPA, as the free fatty acid (EPA-FFA), has chemopreventative efficacy in patients with familial adenomatous polyposis (FAP), in a randomised, double-blind, placebo-controlled trial. METHODS: Patients undergoing endoscopic surveillance of their retained rectum postcolectomy were randomised to EPA-FFA (SLA Pharma) 2 g daily or placebo for 6 months. The number and size of polyps in an area of mucosa defined by a tattoo were determined before and after intervention. Global rectal polyp burden was scored (-1, 0, +1) by examination of video endoscopy records. Mucosal fatty acid content was measured by gas chromatography-mass spectrometry. RESULTS: 55 patients with FAP were evaluated by an intention-to-treat analysis (EPA-FFA 28, placebo 27). Treatment with EPA-FFA for 6 months was associated with a mean 22.4% (95% CI 5.1% to 39.6%) reduction in polyp number (p=0.012) and a 29.8% (3.6% to 56.1%) decrease in the sum of polyp diameters (p=0.027). Global polyp burden worsened over 6 months in the placebo group (-0.34) unlike the EPA-FFA group (+0.09, difference 0.42 (0.10-0.75), p=0.011). EPA-FFA treatment led to a mean 2.6-fold increase in mucosal EPA levels (p=0.018 compared with placebo). EPA-FFA was well tolerated with an incidence of adverse events similar to placebo. CONCLUSIONS: EPA-FFA has chemopreventative efficacy in FAP, to a degree similar to that previously observed with selective cyclo-oxygenase-2 inhibitors. EPA holds promise as a colorectal cancer chemoprevention agent with a favourable safety profile. PMID- 20348369 TI - Effects of oil source and fish oil addition on ruminal biohydrogenation of fatty acids and conjugated linoleic acid formation in beef steers fed finishing diets. AB - Four Hereford steers (500 +/- 4.5 kg of BW) cannulated in the proximal duodenum were used to evaluate the effects of vegetable oil source or fish oil quantity on ruminal biohydrogenation (BH) and CLA outflow. Steers were fed 1 of 4 treatment diets in a 2 x 2 factorial arrangement of treatments (oil source: canola vs. corn oil; fish oil quantity: 0 or 1%) in a 4 x 4 Latin square design. The remainder of the diet included chopped bermudagrass hay, dry-rolled corn, and protein/mineral supplement. Duodenal samples were collected for 4 d after 11-d diet adaptation periods. Data were analyzed with animal, period, oil source, fish oil, and 2-way interaction among oil source and fish oil quantity in the model. All interactions among oil source and fish oil inclusion were nonsignificant with the exception of trans-11 vaccenic acid (TVA) and trans-9 octadecenoic acid. Intake and duodenal flow of total long-chain fatty acids did not differ between treatments. Apparent ruminal DM digestibility was not altered by oil source or fish oil inclusion. Apparent ruminal digestion of fatty acids did not differ among oil sources but was increased (P = 0.03) with fish oil supplementation. Ruminal BH of oleic and linolenic acids was increased (P = 0.01) for diets containing supplemental canola oil compared with corn oil. Ruminal BH of linoleic acid was greater (P = 0.01) for diets containing supplemental corn oil compared with canola oil. Fish oil addition reduced (P = 0.01) oleic acid BH but did not alter (P > 0.26) linoleic or linolenic acid BH. Duodenal flow of palmitic acid was greater (P = 0.05) for steers supplemented with corn oil compared with canola oil. Fish oil inclusion in the diet increased (P = 0.01) flow of n-3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), trans-10 octadecenoic acid, trans 12 octadecenoic acid, and cis-9, trans-11 CLA. Trans-9 octadecenoic acid and TVA flows to the duodenum were increased (P = 0.01) when fish oil was included in the canola oil-supplemented diet; however, no changes were observed when fish oil was included in the corn oil-supplemented diet (P of interaction = 0.06 and 0.08). Fish oil inclusion increased the outflow of n-3 fatty acids, trans-10 octadecenoic acid, and the majority of CLA isomers including cis-9, trans-11. These results suggest that fish oil addition alters ruminal formation of BH intermediates that is dependent on oil source supplemented in the diet. PMID- 20348370 TI - Meta-analysis of the effect of the halothane gene on 6 variables of pig meat quality and on carcass leanness. AB - Technological meat quality is a significant economic factor in pork production, and numerous publications have shown that it is strongly influenced both by genetic status and by rearing and slaughter conditions. The quality of meat is often described by meat pH at different times postmortem, as well as by color and drip loss, whereas carcass quality is often characterized by lean percentage. A meta-analysis of findings relating to 3,530 pigs reported in 23 publications was carried out to assess the effects of the halothane gene, sex, breed, and slaughter weight of animals on 7 selected variables: pH at 45 min postmortem, ultimate pH, reflectance (L*-value), redness (a*-value), yellowness (b*-value), drip loss, and lean percentage. Two statistical methods were used in the meta analysis: the method of effect size and the better known random effects model. The method of effect size was associated with Markov chain Monte Carlo techniques for implementing Bayesian hierarchical models to avoid the problems of limited data and publication bias. The results of our meta-analysis showed that the halothane genotype had a significant effect on all analyzed pork quality variables. Between-study variance was evaluated with the Cochran (1954) Q-test of heterogeneity. Meta-regression was used to explain this variance, with covariates such as breed, sex, slaughter weight, and fasting duration being integrated into different regression models. The halothane gene effect was associated with the breed effect only for the following variables: L*-value, b*-value, and drip loss. Slaughter weight contributed significantly only to the explanation of differences in ultimate pH between homozygous genotypes. In response to inconsistencies reported in the literature regarding the difference between the genotypes NN and Nn, results of the meta-analysis showed that the difference between these 2 genotypes was significant for all the analyzed variables except the a*-value. PMID- 20348371 TI - Effect of dietary n-3 fatty acids (fish oils) on boar reproduction and semen quality. AB - The aim of this study was to evaluate the effects of dietary supplementation with different fish oils (rich in PUFA) vs. hydrogenated animal fat (SFA) on semen production and quality, fatty acid composition, and preservation properties in boars under controlled and commercial conditions. In Exp. 1 (in a research station), 44 boars, allocated to 4 dietary treatments, received daily 2.5 kg of basal diet with a supplement of 1) 62 g of hydrogenated animal fat (AF, n = 12); 2) 60 g of menhaden oil containing 18% docosahexanoic acid (DHA) and 15% eicosapentanoic acid (EPA; MO, n = 11); 3) 60 g of tuna oil containing 33% DHA and 6.5% EPA (TO, n = 11); and 4) 60 g of menhaden oil and 2 mg/kg of biotin (MO+B, n = 10). Biotin is a critical factor in the elongation of PUFA. Semen was collected according to 3 successive phases: phase 1 (twice per week for 4 wk); phase 2 (daily collection for 2 wk); and phase 3 (twice per week for 10 wk). Experiment 2 was conducted in commercial conditions; 222 boars were randomly allocated to AF, MO, and TO treatments. Semen was collected twice weekly over a 6 mo period. All diets were balanced to be iso-energetic and provided an equivalent of 989 mg of vitamin E per day. Classical measurements of sperm quantity and quality were done for both experiments. Experiment 1 showed, after 28 wk of supplementation, a massive transfer of n-3 PUFA into sperm from boars fed fish oil diets (MO and TO). No differences were observed among dietary treatments for libido (P > 0.30), sperm production (P > 0.20), or percentage of motile cell (P > 0.20). Unexpectedly, MO+B diet reduced the percentage of normal sperm compared with the other treatments (P < 0.03). In conclusion, although it modified the fatty acid composition of sperm, supplementation of boars with dietary fish oils, rich in long chain n-3 fatty acids, did not influence semen production or quality postejaculation. PMID- 20348372 TI - Application of biological simulation models in estimating feed efficiency of finishing steers. AB - Data on individual daily feed intake, BW at 28-d intervals, and carcass composition were obtained on 1,212 crossbred steers. Within-animal regressions of cumulative feed intake and BW on linear and quadratic days on feed were used to quantify initial and ending BW, average daily observed feed intake (OFI), and ADG over a 120-d finishing period. Feed intake was predicted (PFI) with 3 biological simulation models (BSM): a) Decision Evaluator for the Cattle Industry, b) Cornell Value Discovery System, and c) NRC update 2000, using observed growth and carcass data as input. Residual feed intake (RFI) was estimated using OFI (RFI(EL)) in a linear statistical model (LSM), and feed conversion ratio (FCR) was estimated as OFI/ADG (FCR(E)). Output from the BSM was used to estimate RFI by using PFI in place of OFI with the same LSM, and FCR was estimated as PFI/ADG. These estimates were evaluated against RFI(EL) and FCR(E). In a second analysis, estimates of RFI were obtained for the 3 BSM as the difference between OFI and PFI, and these estimates were evaluated against RFI(EL). The residual variation was extremely small when PFI was used in the LSM to estimate RFI, and this was mainly due to the fact that the same input variables (initial BW, days on feed, and ADG) were used in the BSM and LSM. Hence, the use of PFI obtained with BSM as a replacement for OFI in a LSM to characterize individual animals for RFI was not feasible. This conclusion was also supported by weak correlations (<0.4) between RFI(EL) and RFI obtained with PFI in the LSM, and very weak correlations (<0.13) between RFI(EL) and FCR obtained with PFI. In the second analysis, correlations (>0.89) for RFI(EL) with the other RFI estimates suggest little difference between RFI(EL) and any of these RFI estimates. In addition, results suggest that the RFI estimates calculated with PFI would be better able to identify animals with low OFI and small ADG as inefficient compared with RFI(EL). These results may be due to the fact that computer models predict performance on an individual animal basis in contrast to a LSM, which estimates a fixed relationship for all animals; hence, the BSM may provide RFI estimates that are closer to the true biological efficiency of animals. In addition, BSM may facilitate comparisons across different data sets and provide more accurate estimates of efficiency in small data sets where errors would be greater with a LSM. PMID- 20348373 TI - Beef symposium: population data analyses to evaluate trends in animal production systems. PMID- 20348374 TI - Factors affecting preovulatory follicle diameter and ovulation rate after gonadotropin-releasing hormone in postpartum beef cows. Part II: Anestrous cows. AB - There is large variation in dominant follicle diameter at the time of GnRH induced ovulation in the CO-Synch protocol [a first GnRH injection on d -9 (GnRH1), followed by PGF(2alpha) on d -2, and a second GnRH injection (GnRH2) with timed AI on d 0], and the reason for the presence of small dominant follicles at GnRH2 is not known. Our hypothesis was that ovulatory response to GnRH1 and progesterone exposure [controlled intravaginal drug-releasing insert (CIDR; EAZI-Breed, Pfizer Animal Health, New York, NY)] would affect ovulatory follicle size at GnRH2 in anestrous cows. This study used a 2 x 2 factorial arrangement of treatments in which anestrous suckled beef cows (n = 55) either ovulated (Ov1+) or failed to ovulate (Ov1-) after GnRH1 and either received (CIDR+) or did not receive (CIDR-) a 7-d CIDR treatment (from GnRH1 to PGF(2alpha)), resulting in the following treatment groups: Ov1+CIDR+, Ov1-CIDR+, Ov1+CIDR-, and Ov1-CIDR- (n = 9, 17, 11, and 18, respectively). The Ov1+ cows had larger follicles at GnRH2 (12.3 vs. 11.0 mm; P = 0.04), a decreased proportion of small follicles within cows that ovulated to GnRH2 (2/16 vs. 14/23; P = 0.003), and a similar growth rate of the ovulatory follicle from d -5 to 0 (d 0 = GnRH2; 1.1 +/- 0.06 vs. 1.1 +/- 0.07 mm/d; P = 0.99) compared with Ov1- cows. Administration of a CIDR had no effect on follicle diameter at GnRH2 (11.8 vs. 11.2 mm; P = 0.3), proportion of small ovulatory follicles at GnRH2 (7/19 vs. 9/20; P = 0.6), and follicular growth rate from d -5 to 0 (d 0 = GnRH2; 1.2 +/- 0.07 vs. 1.1 +/- 0.07 mm/d; P = 0.76). Administration of a CIDR, but not ovulation to GnRH1, increased follicle growth from d -2 to 0 (d 0 = GnRH2; P = 0.03 and 0.9, respectively). Large follicles (>11 mm) had a similar growth rate from d -5 to 0 (d 0 = GnRH2; P = 0.44) compared with small follicles (1.1 +/- 0.07 vs. 1.2 +/- 0.07 mm/d), but the large ovulatory follicles were larger at d 5 compared with small ovulatory follicles (P < 0.001). Follicle diameter was positively correlated with serum concentrations of estradiol at GnRH2 (r = 0.622; P < 0.0001). In summary, ovulation to GnRH1, but not CIDR administration, resulted in increased dominant follicle diameter at GnRH2 in anestrous suckled beef cows. Large follicles were already larger 5 d before GnRH2 but grew at a rate similar to small follicles; follicle size was positively correlated with serum concentrations of estradiol at the time of GnRH-induced ovulation. PMID- 20348375 TI - Fate and transport of zoonotic, bacterial, viral, and parasitic pathogens during swine manure treatment, storage, and land application. AB - Members of the public are always somewhat aware of foodborne and other zoonotic pathogens; however, recent illnesses traced to produce and the emergence of pandemic H1N1 influenza virus have increased the scrutiny on all areas of food production. The Council for Agricultural Science and Technology has recently published a comprehensive review of the fate and transport of zoonotic pathogens that can be associated with swine manure. The majority of microbes in swine manure are not zoonotic, but several bacterial, viral, and parasitic pathogens have been detected. Awareness of the potential zoonotic pathogens in swine manure and how treatment, storage, and handling affect their survival and their potential to persist in the environment is critical to ensure that producers and consumers are not at risk. This review discusses the primary zoonotic pathogens associated with swine manure, including bacteria, viruses, and parasites, as well as their fate and transport. Because the ecology of microbes in swine waste is still poorly described, several recommendations for future research are made to better understand and reduce human health risks. These recommendations include examination of environmental and ecological conditions that contribute to off farm transport and development of quantitative risk assessments. PMID- 20348376 TI - Establishing an appropriate mode of comparison for measuring the performance of marbling score output from video image analysis beef carcass grading systems. AB - A beef carcass instrument grading system that improves accuracy and consistency of marbling score (MS) evaluation would have the potential to advance value-based marketing efforts and reduce disparity in quality grading among USDA graders, shifts, and plants. The objectives of this study were to use output data from the Video Image Analysis-Computer Vision System (VIA-CVS, Research Management Systems Inc., Fort Collins, CO) to develop an appropriate method by which performance of video image analysis MS output could be evaluated for accuracy, precision, and repeatability for purposes of seeking official USDA approval for using an instrument in commerce to augment assessment of quality grade, and to use the developed standards to gain approval for VIA-CVS to assist USDA personnel in assigning official beef carcass MS. An initial MS output algorithm was developed (phase I) for the VIA-CVS before 2 separate preliminary instrument evaluation trials (phases II and III) were conducted. During phases II and III, a 3-member panel of USDA expert graders independently assigned MS to 1,068 and 1,242 stationary carcasses, respectively. Mean expert MS was calculated for each carcass. Additionally, a separate 3-member USDA expert panel developed a consensus MS for each carcass in phase III. In phase II, VIA-CVS stationary triple-placement and triple-trigger instrument repeatability values (n = 262 and 260, respectively), measured as the percentage of total variance explained by carcasses, were 99.9 and 99.8%, respectively. In phases II and III, 95% of carcasses were assigned expert MS for which differences between individual expert MS, and for which the consensus MS in phase III only, was < or = 96 MS units. Two differing approaches to simple regression analysis, as well as a separate method comparability analysis that accommodates error in both dependent and independent variables, were used to assess accuracy and precision of instrument MS predictions vs. mean expert MS. Method-comparability analysis was more appropriate in assessing the bias and precision of instrument MS predictions. Ether-extractable fat percentages (n = 257; phase II) differed among MS (P < 0.05) but were not suitable to predict or validate assigned MS. The performance and reproducibility of expert MS assignment in future evaluations was considered, and an official USDA performance standard was established, to which an instrument must conform to be approved for official on-line MS assessment. The VIA-CVS subsequently was approved to assign MS to carcasses on-line after completion of a 2006 USDA instrument approval trial conducted according to methods developed during completion of this study. PMID- 20348377 TI - A multivariate nonlinear mixed effects method for analyzing energy partitioning in growing pigs. AB - Simultaneous equations have become increasingly popular for describing the effects of nutrition on the utilization of ME for protein (PD) and lipid deposition (LD) in animals. The study developed a multivariate nonlinear mixed effects (MNLME) framework and compared it with an alternative method for estimating parameters in simultaneous equations that described energy metabolism in growing pigs, and then proposed new PD and LD equations. The general statistical framework was implemented in the NLMIXED procedure in SAS. Alternative PD and LD equations were also developed, which assumed that the instantaneous response curve of an animal to varying energy supply followed the law of diminishing returns behavior. The Michaelis-Menten function was adopted to represent a biological relationship in which the affinity constant (k) represented the sensitivity of PD to ME above maintenance. The approach accommodated inclusion of a PD potential (PD(Potential)) concept. This was described by a Gompertz function, which was parameterized in terms of the maximum rate of PD (PD(Max)) and corresponding BW (BW(PDMax)) at that point. Metabolizable energy for LD was equated to the difference between ME intake and the sum of ME used for maintenance and PD. Metabolizable energy designated for PD and LD was used, with efficiencies k(p) and k(f), respectively. The new equations were compared with the van Milgen and Noblet (1999) equations using 2 comprehensive data sets on energy metabolism in growing pigs. The 2 equation sets were evaluated using information criteria, which showed that the new equations performed best for data set II, whereas the reverse was true for the first. For the data set I population, estimates for k(p) and k(f) were 0.57 (SE = 0.05) and 0.84 (SE = 0.03), respectively. Maintenance was quantified as 1.10 (SE = 0.08) MJ/d*kg(0.55). The animal variation in the parameter k(p) was estimated to be 6% CV. The animal variation in PD(Max) and k(f) was estimated to be 9 and 10% of the population estimates, respectively. It was concluded that application of the MNLME framework was superior to the multivariate nonlinear regression model because the MNLME method accounted for correlated errors associated with PD and LD measurements and could also include the random effect of animal. It is recommended that multivariate models used to quantify energy metabolism in growing pigs should account for animal variability and correlated measurement errors. PMID- 20348378 TI - Technical note: Analysis of total lipid and triacylglycerol content in small liver biopsy samples in cattle. AB - A procedure is described for analyzing total lipid (TL) and triacylglycerol (TAG) in 2 sequential steps using small amounts (<100 mg) of bovine liver tissue. The TL was measured gravimetrically and TAG was measured enzymatically in the TL extract, using an automated analyzer. For gravimetric TL determination in milligrams per gram of liver fresh weight (FW), TL was extracted from homogenized tissue samples with hexane:isopropanol (at 20 degrees C, 24 h, constant agitation). The routine method was modified by adding a second hexane extraction step to optimize lipid extraction. The dry lipid extract was dissolved in hexane and aliquoted according to TL content for TAG analysis. An extra incubation period of 16 h was included for complete hydrolysis of TAG, using microbial lipase and nonaethylene glycol monododecyl ether detergent, before TAG was measured enzymatically using commercial test kits. Triolein was used as an internal standard. Repeated TL analysis (n = 3) of liver specimens from 10 cows (range, 40 to 314 mg/g of FW) yielded a mean CV of 2.2%, whereas repeated TAG analysis (range, 4 to 260 mg/g of FW) yielded a mean intraday CV of 2.5% (n = 5) and a mean interday CV of 3.4% (n = 4). Intraday (n = 5) and interday (n = 4) CV for repeated TAG analysis in triolein standards were <1 and <3%, respectively. Recovery of TAG in triolein standards varied between 99 and 103%. In part 2 of the experiment, hepatic TL and TAG were measured in 150 German Holstein cows to verify the test method in a large sample size. For repeated hepatic TL (n = 3) and TAG (n = 5) determination, mean CV of <2.8 and <1.5%, respectively, were found. The proportion of TAG relative to TL increased linearly to a breakpoint of approximately 100 mg TL/g of FW, at which point it reached a plateau at approximately 68%, indicating an accumulation of other lipid fractions in hepatic tissue with hepatic TL above the breakpoint. Calculation of hepatic TAG from TL was reasonably accurate when a 2-slope linear broken-line model (r(2) = 0.98) was used. Above a TL of approximately 40 mg/g of FW, calculated TAG values deviated by only +/-15% from measured hepatic TAG. PMID- 20348379 TI - Growth and development symposium: fetal programming in animal agriculture. PMID- 20348380 TI - Phosphorus requirement and excretion of finishing beef cattle fed different concentrations of phosphorus. AB - Phosphorus is an expensive nutrient to supplement, and excess may lead to manure P challenges. Therefore, minimizing dietary P to meet requirements is important. Two experiments were conducted to determine the P requirement of finishing cattle (Exp. 1) and to evaluate the effects of feeding different P concentrations on the quantity and route of P excretion (Exp. 2). In Exp. 1, 60 heifers (BW = 278 kg +/ 17 kg) were individually fed 1 of 5 dietary P concentrations (0.10, 0.17, 0.24, 0.31, or 0.38% P). Cattle performance, plasma P concentration, bone characteristics, and bone P concentration were used to determine the P requirement. Intake and ADG increased quadratically (P < 0.01) as dietary P increased. Plasma P in heifers receiving the 0.10% treatment was less (P < 0.01) than the other treatments and suggested that these heifers were experiencing a P deficiency. Total ash weight of the phalanx bones increased linearly (P < 0.01) as dietary P increased. In Exp. 2 using a 5 x 5 Latin square design, 5 different diets varying in P concentration (0.12, 0.27, 0.42, 0.30, and 0.36% P) were fed to steers to evaluate route and quantity of P excreted. Steers excreted little (1.78 g/d on average) P in the urine as a percentage of total P excretion. Steers on the 0.12% P diet excreted very little P in urine (0.50 g/d). Excretion of P was less (P < 0.05) for the cattle fed 0.12% P compared with all other treatments. Results from cattle performance, plasma P concentrations, and bone characteristics indicate that the heifers fed 0.10% P were experiencing a deficiency and the P requirement of finishing heifers is between 0.10 and 0.17% P. Dietary P concentrations of 0.10 to 0.17% P resulted in decreased P excretion. Supplementation of mineral P is unnecessary in grain-based feedlot diets because dietary P will greatly exceed the requirements (<0.17%). PMID- 20348381 TI - Fine-mapping quantitative trait loci for twinning rate on Bos taurus chromosome 14 in North American Holsteins. AB - A previous genome-wide search with a moderate-density 10,000-SNP set identified many marker associations with twinning rate on BTA14 through either single-marker analysis or combined linkage-linkage disequilibrium (LLD; haplotype) analysis. The objective of the current study was to fine-map putative QTL using a more densely populated marker map and both a larger and an independent set of phenotypic data. Holstein bulls (n = 921) from 100 paternal half-sib families were genotyped for 129 SNP markers that included both original and additionally selected markers for increasing marker density in the targeted 34 megabase region. Twinning rate predicted transmitting abilities were calculated using calving records from 1994 to 1998 (data I) and 1999 to 2006 (data II), and the underlying liability scores from threshold model analysis were used as the trait in marker association analyses. The previous analysis used 201 bulls with daughter records in data I. In the current analysis, this was increased to 434, providing a revised estimate of effect and significance. Bulls with daughter records in data II totaled 851, and analysis of these data provided an opportunity for an independent analysis separate from data I. Single-marker association and LLD analyses were performed. Fifteen significant single-marker associations were found (minimally exceeding P < 8.74 x 10(-3)) to concur between data sets. Three and 12 regions in data I and data II, respectively, showed positive results for the presence of QTL from LLD analysis (P < 0.001) within the respective data sets. After combining results from single-marker association, LLD analysis, and model-building strategies, 3 QTL were identified on BTA14. Based on single-marker results from data II, BTA14 harbors QTL responsible for approximately 24% of the variation in twinning rate predicted transmitting ability. PMID- 20348382 TI - Effect of thiamine concentration on animal health, feedlot performance, carcass characteristics, and ruminal hydrogen sulfide concentrations in lambs fed diets based on 60% distillers dried grains plus solubles. AB - Limited data are available regarding the influence of thiamine supplementation on the incidence of polioencephalomalacia (PEM) in lambs fed diets containing increased concentrations of S in the diet (>0.7%). Therefore, our objective was to evaluate the influence of thiamine supplementation on feedlot performance, carcass quality, ruminal hydrogen sulfide gas concentrations, and incidence of PEM in lambs fed a finishing diet containing 60% distillers dried grains with solubles (DDGS; DM basis). Two studies were conducted using completely randomized designs to evaluate the influence of concentration of thiamine supplementation. Study 1 used 240 lambs fed in 16 pens, whereas study 2 used 55 individually fed lambs. Lamb finishing diets contained 60% DDGS, which resulted in a dietary S concentration of 0.73% (DM basis). Treatments diets were based on the amount of supplemental thiamine provided: 1) no supplemental thiamine (CON), 2) 50 mg/animal per day (LO), 3) 100 mg/animal per day (MED), or 4) 150 mg/animal per day (HI). Additionally, in study 2, a fifth treatment was included, which contained 0.87% S (DM basis; increased S provided by addition of dilute sulfuric acid) and provided 150 mg of thiamine/animal per day (HI+S). In study 1, ADG decreased quadratically (P = 0.04), with lambs fed the CON, LO, and MED diets gaining BW at a greater rate than lambs fed the HI diet. In study 1, DMI responded quadratically (P < 0.01), whereas G:F tended to differ linearly (P = 0.08) to concentration of thiamine supplementation, with MED lambs having greater DMI and decreased G:F. No differences (P > or = 0.17) in lamb performance were observed in study 2. In both studies, most carcass characteristics were unaffected, with the exception of a tendency for decreased carcass conformation (study 1; P = 0.09) and greater flank streaking (study 2; P = 0.03). No differences in ruminal hydrogen sulfide concentration (P > 0.05) among treatments were apparent until d 10, at which point lambs fed the LO diet had less hydrogen sulfide concentrations than all other treatments. Lambs fed HI had the greatest concentrations of hydrogen sulfide on d 31 (1.07 g of hydrogen sulfide /m(3); P < 0.009). Ruminal pH did not differ (P = 0.13) and averaged 5.6 +/- 0.06. No clinical cases of PEM were observed during the course of either study. The use of thiamine as a dietary additive to aid in the prevention of PEM in finishing lambs does not appear to be necessary under the conditions of this study. PMID- 20348383 TI - Interaction of the Aspergillus nidulans microtubule-organizing center (MTOC) component ApsB with gamma-tubulin and evidence for a role of a subclass of peroxisomes in the formation of septal MTOCs. AB - Peroxisomes are a diverse class of organelles involved in different physiological processes in eukaryotic cells. Although proteins imported into peroxisomes carry a peroxisomal targeting sequence at the C terminus (PTS1) or an alternative one close to the N terminus (PTS2), the protein content of peroxisomes varies drastically. Here we suggest a new class of peroxisomes involved in microtubule (MT) formation. Eukaryotic cells assemble MTs from distinct points in the cell. In the fungus Aspergillus nidulans, septum-associated microtubule-organizing centers (sMTOCs) are very active in addition to the spindle pole bodies (SPBs). Previously, we identified a novel MTOC-associated protein, ApsB (Schizosaccharomyces pombe mto1), whose absence affected MT formation from sMTOCs more than from SPBs, suggesting that the two protein complexes are organized differently. We show here that sMTOCs share at least two further components, gamma-tubulin and GcpC (S. pombe Alp6) with SPBs and found that ApsB interacts with gamma-tubulin. In addition, we discovered that ApsB interacts with the Woronin body protein HexA and is targeted to a subclass of peroxisomes via a PTS2 peroxisomal targeting sequence. The PTS2 motif was necessary for function but could be replaced with a PTS1 motif at the C terminus of ApsB. These results suggest a novel function for a subclass of peroxisomes in cytoskeletal organization. PMID- 20348384 TI - Fluconazole transport into Candida albicans secretory vesicles by the membrane proteins Cdr1p, Cdr2p, and Mdr1p. AB - A major cause of azole resistance in Candida albicans is overexpression of CDR1, CDR2, and/or MDR1, which encode plasma membrane efflux pumps. To analyze the catalytic properties of these pumps, we used ACT1- and GAL1-regulated expression plasmids to overexpress CDR1, CDR2, or MDR1 in a C. albicans cdr1 cdr2 mdr1-null mutant. When the genes of interest were expressed, the resulting transformants were more resistant to multiple azole antifungals, and accumulated less [(3)H]fluconazole intracellularly, than empty-vector controls. Next, we used a GAL1-regulated dominant negative sec4 allele to cause cytoplasmic accumulation of post-Golgi secretory vesicles (PGVs), and we found that PGVs isolated from CDR1-, CDR2-, or MDR1-overexpressing cells accumulated much more [(3)H]fluconazole than did PGVs from empty-vector controls. The K(m)s (expressed in micromolar concentrations) and V(max)s (expressed in picomoles per milligram of protein per minute), respectively, for [(3)H]fluconazole transport were 0.8 and 0.91 for Cdr1p, 4.3 and 0.52 for Cdr2p, and 3.5 and 0.59 for Mdr1p. [(3)H]fluconazole transport by Cdr1p and Cdr2p required ATP and was unaffected by carbonyl cyanide 3-chlorophenylhydrazone (CCCP), whereas [(3)H]fluconazole transport by Mdr1p did not require ATP and was inhibited by CCCP. [(3)H]fluconazole uptake by all 3 pumps was inhibited by all other azoles tested, with 50% inhibitory concentrations (IC(50)s; expressed as proportions of the [(3)H]fluconazole concentration) of 0.2 to 5.6 for Cdr1p, 0.3 to 3.1 for Cdr2p, and 0.3 to 3.1 for Mdr1p. The methods used in this study may also be useful for studying other plasma membrane transporters in C. albicans and other medically important fungi. PMID- 20348385 TI - Constitutive secretion in Tetrahymena thermophila. AB - The growth, survival, and life cycle progression of the freshwater ciliated protozoan Tetrahymena thermophila are responsive to protein signals thought to be released by constitutive secretion. In addition to providing insights about ciliate communication, studies of constitutive secretion are of interest for evaluating the utility of T. thermophila as a platform for the expression of secreted protein therapeutics. For these reasons, we undertook an unbiased investigation of T. thermophila secreted proteins using wild-type and secretion mutant strains. Extensive tandem mass spectrometry analyses of secretome samples were performed. We identified a total of 207 secretome proteins, most of which were not detected in a set of abundant whole-cell protein identifications. Numerous proteases and other hydrolases were secreted from cells grown in rich medium but not cells transferred to a nutrient starvation condition. On the other hand, we detected the starvation-enhanced secretion of a small number of cytosolic proteins, suggestive of an exosome-like pathway in T. thermophila. Subsets of proteins from the T. thermophila regulated secretion pathway were detected with differential representation across strains and culture conditions. Finally, many secretome proteins had a predicted N-terminal signal sequence but no other annotated characteristic or functional classification. Our work provides the first comprehensive analysis of secreted proteins in T. thermophila and establishes the groundwork for future studies of constitutive protein secretion biology and biotechnology in ciliates. PMID- 20348386 TI - Contribution of peroxisomes to secondary metabolism and pathogenicity in the fungal plant pathogen Alternaria alternata. AB - The filamentous fungus Alternaria alternata includes seven pathogenic variants (pathotypes) which produce different host-selective toxins and cause diseases on different plants. The Japanese pear pathotype produces the host-selective AK toxin, an epoxy-decatrienoic acid ester, and causes black spot of Japanese pear. Previously, we identified four genes, AKT1, AKT2, AKT3, and AKTR, involved in AK toxin biosynthesis. AKT1, AKT2, and AKT3 encode enzyme proteins with peroxisomal targeting signal type 1 (PTS1)-like tripeptides, SKI, SKL, and PKL, respectively, at the C-terminal ends. In this study, we verified the peroxisome localization of Akt1, Akt2, and Akt3 by using strains expressing N-terminal green fluorescent protein (GFP)-tagged versions of the proteins. To assess the role of peroxisome function in AK-toxin production, we isolated AaPEX6, which encodes a peroxin protein essential for peroxisome biogenesis, from the Japanese pear pathotype and made AaPEX6 disruption-containing transformants from a GFP-Akt1-expressing strain. The DeltaAaPEX6 mutant strains did not grow on fatty acid media because of a defect in fatty acid beta oxidation. The import of GFP-Akt1 into peroxisomes was impaired in the DeltaAaPEX6 mutant strains. These strains completely lost AK toxin production and pathogenicity on susceptible pear leaves. These data show that peroxisomes are essential for AK-toxin biosynthesis. The DeltaAaPEX6 mutant strains showed a marked reduction in the ability to cause lesions on leaves of a resistant pear cultivar with defense responses compromised by heat shock. This result suggests that peroxisome function is also required for plant invasion and tissue colonization in A. alternata. We also observed that mutation of AaPEX6 caused a marked reduction of conidiation. PMID- 20348387 TI - Characterization of the Roco protein family in Dictyostelium discoideum. AB - The Roco family consists of multidomain Ras-GTPases that include LRRK2, a protein mutated in familial Parkinson's disease. The genome of the cellular slime mold Dictyostelium discoideum encodes 11 Roco proteins. To study the functions of these proteins, we systematically knocked out the roco genes. Previously described functions for GbpC, Pats1, and QkgA (Roco1 to Roco3) were confirmed, while novel developmental defects were identified in roco4- and roco11-null cells. Cells lacking Roco11 form larger fruiting bodies than wild-type cells, while roco4-null cells show strong developmental defects during the transition from mound to fruiting body; prestalk cells produce reduced levels of cellulose, leading to unstable stalks that are unable to properly lift the spore head. Detailed phylogenetic analysis of four slime mold species reveals that QkgA and Roco11 evolved relatively late by duplication of an ancestor roco4 gene (later than approximately 300 million years ago), contrary to the situation with other roco genes, which were already present before the split of the common ancestor of D. discoideum and Polysphondylium pallidum (before approximately 600 million years ago). Together, our data show that the Dictyostelium Roco proteins serve a surprisingly diverse set of functions and highlight Roco4 as a key protein for proper stalk cell formation. PMID- 20348388 TI - Conserved regulators of mating are essential for Aspergillus fumigatus cleistothecium formation. AB - Sexual reproduction of the human pathogen Aspergillus fumigatus (teleomorph: Neosartorya fumigata) was assumed to be absent or cryptic until recently, when fertile crosses among geographically restricted environmental isolates were described. Here, we provide evidence for mating, fruiting body development, and ascosporogenesis accompanied by genetic recombination between unrelated, clinical isolates of A. fumigatus, and this evidence demonstrates the generality and reproducibility of this long-time-undisclosed phase in the life cycle of this heterothallic fungus. Successful mating requires the presence of both mating-type idiomorphs MAT1-1 and MAT1-2, as does expression of genes encoding factors presumably involved in this process. Moreover, analysis of an A. fumigatus mutant deleted for the nsdD gene suggests a role of this conserved regulator of cleistothecium development in hyphal fusion and hence heterokaryon formation. PMID- 20348389 TI - Analysis of the high-affinity iron uptake system at the Chlamydomonas reinhardtii plasma membrane. AB - Multicopper ferroxidases play a vital role in iron metabolism in bacteria, fungi, algae, and mammals. Saccharomyces cerevisiae utilizes a channeling mechanism to couple the ferroxidase activity of Fet3p to Fe(3+) transport into the cell by Ftr1p. In contrast, the mechanisms by which mammals couple the ferroxidase reaction to iron trafficking is unclear. The human ferroxidases ceruloplasmin and hephaestin are twice the size of Fet3p and interact with proteins that are not expressed in fungi. Chlamydomonas FOX1 is a homolog of the human ferroxidases but likely supports iron uptake in a manner similar to that of yeast, since Chlamydomonas reinhardtii expresses a ferric iron permease homolog, FTR1. The results presented support this hypothesis. We show that FOX1 is trafficked to the plasma membrane and is oriented with its multicopper oxidase/ferroxidase domain in the exocytoplasmic space. Our analysis of FTR1 indicates its topology is similar to that of S. cerevisiae Ftr1p, with a potential exocytoplasmic iron channeling motif and two potential iron permeation motifs in membrane-spanning regions. We demonstrate that high-affinity iron uptake is dependent on FOX1 and the copper status of the cell. Kinetic inhibition of high-affinity iron uptake by a ferric iron chelator does not reflect the strength of the chelator, supporting a ferric iron channeling mechanism for high-affinity iron uptake in Chlamydomonas. Last, recombinant FOX1 (rFOX1) has been isolated in a partially holo form that exhibits the UV-visible absorbance spectrum of a multicopper oxidase and the catalytic activity of a ferroxidase. PMID- 20348390 TI - Marker fusion tagging, a new method for production of chromosomally encoded fusion proteins. AB - A new gene-tagging method (marker fusion tagging [MFT]) is demonstrated for Neurospora crassa and Magnaporthe oryzae. Translational fusions between the hygromycin B resistance gene and various markers are inserted into genes of interest by homologous recombination to produce chromosomally encoded fusion proteins. This method can produce tags at any position and create deletion alleles that maintain N- and C-terminal sequences. We show the utility of MFT by producing enhanced green fluorescent protein (EGFP) tags in proteins localized to nuclei, spindle pole bodies, septal pore plugs, Woronin bodies, developing septa, and the endoplasmic reticulum. PMID- 20348391 TI - Long-term study of indolent adult T-cell leukemia-lymphoma. AB - The long-term prognosis of indolent adult T-cell leukemia-lymphoma (ATL) is not clearly elucidated. From 1974 to 2003, newly diagnosed indolent ATL in 90 patients (65 chronic type and 25 smoldering type) was analyzed. The median survival time was 4.1 years; 12 patients remained alive for more than 10 years, 44 progressed to acute ATL, and 63 patients died. The estimated 5-, 10-, and 15 year survival rates were 47.2%, 25.4%, and 14.1%, respectively, with no plateau in the survival curve. Although most patients were treated with watchful waiting, 12 patients were treated with chemotherapy. Kaplan-Meier analyses showed that advanced performance status (PS), neutrophilia, high concentration of lactate dehydrogenase, more than 3 extranodal lesions, more than 4 total involved lesions, and receiving chemotherapy were unfavorable prognostic factors for survival. Multivariate Cox analysis showed that advanced PS was a borderline significant independent factor in poor survival (hazard ratio, 2.1, 95% confidence interval, 1.0-4.6; P = .06), but it was not a factor when analysis was limited to patients who had not received chemotherapy. The prognosis of indolent ATL in this study was poorer than expected. These findings suggest that even patients with indolent ATL should be carefully observed in clinical practice. Further studies are required to develop treatments for indolent ATL. PMID- 20348392 TI - CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells. AB - Recent studies have shown that anemia is commonly observed after exposure to pathogens or pathogen-derived products, which are recognized via Toll-like receptor 9 (TLR9). In the current study, we demonstrate that CpG oligodeoxynucleotide-2006, a TLR9 ligand with phosphodiester (PO; 2006-PO) but not with the phosphorothioate backbone, selectively inhibits the erythroid growth derived from human CD34(+) cells. The 2006-PO was internalized by the erythroid progenitors within 30 minutes; however, expression of TLR9 mRNA was not detected in these cells. The 2006-PO directly inhibited burst-forming unit-erythroid growth, resulted in the accumulation of cells in S and G(2)/M phases, and increased cell size and frequency of apoptotic cells. These features were similar to those observed in erythroid progenitors infected with human parvovirus B19 that causes pure red cell aplasia. The consensus sequence of 2006-PO was defined as 5'-GTTTTGT-3', which was located in the P6-promoter region of B19 and inhibited erythroid growth in a sequence-specific manner and down-regulated expression of erythropoietin receptor (EPOR) mRNA and EPOR. B19 genome extracted from serum also inhibited erythroid growth and down-regulated expression of EPOR on glycophorin A(+) cells. These results provide a possible insight into our understanding of the mechanisms of human parvovirus B19-mediated inhibition of erythropoiesis. PMID- 20348393 TI - Age-dependent vulnerability to endotoxemia is associated with reduction of anticoagulant factors activated protein C and thrombomodulin. AB - The protein C (PC) pathway is an important anticoagulant mechanism that prevents thrombosis during the systemic inflammatory response. Thrombomodulin (TM), an endothelial cell membrane receptor, accelerates the conversion of PC to activated protein C (APC), which leads to the down-regulation of thrombin production and fibrin formation. Induction of acute endotoxemia in young and aged mice with a low dose of bacterial endotoxin lipopolysaccharide (LPS, 2.5 mg/kg) caused a high mortality rate in aged (80%) but not young (0%) mice. After injection with this dose of LPS, fibrin formation was significantly elevated only in aged mice, plasma APC levels were increased only in young mice, and TM expression was profoundly depressed in the aged. The increased thrombosis, suppressed APC level, and decreased TM expression were not observed in young mice receiving a higher dose of LPS (20 mg/kg), which resulted in a mortality rate (78%) equivalent to that seen in aged mice with the low-dose LPS. Mutant mice with reduced TM showed significantly less plasma APC and increased fibrin formation compared with wild type mice after LPS. These results demonstrate that PC pathway activation is suppressed with aging and is partly responsible for age-associated thrombosis and high mortality during endotoxemia. PMID- 20348394 TI - The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. AB - On-patent and off-patent drugs with previously unrecognized anticancer activity could be rapidly repurposed for this new indication given their prior toxicity testing. To identify such compounds, we conducted chemical screens and identified the antihelmintic flubendazole. Flubendazole induced cell death in leukemia and myeloma cell lines and primary patient samples at nanomolar concentrations. Moreover, it delayed tumor growth in leukemia and myeloma xenografts without evidence of toxicity. Mechanistically, flubendazole inhibited tubulin polymerization by binding tubulin at a site distinct from vinblastine. In addition, cells resistant to vinblastine because of overexpression of P glycoprotein remained fully sensitive to flubendazole, indicating that flubendazole can overcome some forms of vinblastine resistance. Given the different mechanisms of action, we evaluated the combination of flubendazole and vinblastine in vitro and in vivo. Flubendazole synergized with vinblastine to reduce the viability of OCI-AML2 cells. In addition, combinations of flubendazole with vinblastine or vincristine in a leukemia xenograft model delayed tumor growth more than either drug alone. Therefore, flubendazole is a novel microtubule inhibitor that displays preclinical activity in leukemia and myeloma. PMID- 20348395 TI - Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. AB - The anticoagulant factor protein S (PS) has direct cellular activities. Lack of PS in mice causes lethal coagulopathy, ischemic/thrombotic injuries, vascular dysgenesis, and blood-brain barrier (BBB) disruption with intracerebral hemorrhages. Thus, we hypothesized that PS maintains and/or enhances the BBB integrity. Using a BBB model with human brain endothelial cells, we show PS inhibits time- and dose-dependently (half maximal effective concentration [EC(50)] = 27 +/- 3 nM) oxygen/glucose deprivation-induced BBB breakdown, as demonstrated by measurements of the transmonolayer electrical resistance, permeability of endothelial monolayers to dextran (40 kDa), and rearrangement of F-actin toward the cortical cytoskeletal ring. Using Tyro-3, Axl, and Mer (TAM) receptor, tyrosine kinase silencing through RNA interference, specific N-terminus blocking antibodies, Tyro3 phosphorylation, and Tyro3-, Axl- and Mer-deficient mouse brain endothelial cells, we show that Tyro3 mediates PS vasculoprotection. After Tyro3 ligation, PS activated sphingosine 1-phosphate receptor (S1P(1)), resulting in Rac1-dependent BBB protection. Using 2-photon in vivo imaging, we show that PS blocks postischemic BBB disruption in Tyro3(+/+), Axl(-/-), and Mer( /-) mice, but not in Tyro3(-/-) mice or Tyro3(+/+) mice receiving low-dose W146, a S1P(1)-specific antagonist. Our findings indicate that PS protects the BBB integrity via Tyro3 and S1P(1), suggesting potentially novel treatments for neurovascular dysfunction resulting from hypoxic/ischemic BBB damage. PMID- 20348396 TI - A general framework for studying genetic effects and gene-environment interactions with missing data. AB - Missing data arise in genetic association studies when genotypes are unknown or when haplotypes are of direct interest. We provide a general likelihood-based framework for making inference on genetic effects and gene-environment interactions with such missing data. We allow genetic and environmental variables to be correlated while leaving the distribution of environmental variables completely unspecified. We consider 3 major study designs-cross-sectional, case control, and cohort designs-and construct appropriate likelihood functions for all common phenotypes (e.g. case-control status, quantitative traits, and potentially censored ages at onset of disease). The likelihood functions involve both finite- and infinite-dimensional parameters. The maximum likelihood estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Expectation-Maximization (EM) algorithms are developed to implement the corresponding inference procedures. Extensive simulation studies demonstrate that the proposed inferential and numerical methods perform well in practical settings. Illustration with a genome-wide association study of lung cancer is provided. PMID- 20348397 TI - Software for fitting nonstandard proportional subdistribution hazards models. PMID- 20348398 TI - Fibrinogen assays for cardiovascular risk assessment. PMID- 20348399 TI - Identification of the hormone kisspeptin in amniotic fluid. PMID- 20348400 TI - Comparison between gradient gel electrophoresis and nuclear magnetic resonance spectroscopy in estimating coronary heart disease risk associated with LDL and HDL particle size. AB - BACKGROUND: Gradient gel electrophoresis (GGE) and nuclear magnetic resonance (NMR) spectroscopy are both widely accepted methods for measuring LDL and HDL particle size. However, whether or not GGE- or NMR-measured LDL or HDL particle size predicts coronary heart disease (CHD) risk to a similar extent is currently unknown. METHODS: We used GGE and NMR to measure LDL and HDL particle size in a nested case-control study of 1025 incident cases of CHD and 1915 controls from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. The study sample included apparently healthy men and women age 45-79 years followed for an average of 6 years. RESULTS: Pearson correlation coefficients showed that the overall agreement between NMR and GGE was better for the measurement of HDL size (r = 0.78) than for LDL size (r = 0.47). The odds ratio for future CHD among participants in the bottom tertile of LDL size (smallest LDL particles) was 1.35 (95% CI, 1.12-1.63) for GGE and 1.74 (1.41-2.15) for NMR. For HDL size, these respective odds ratios were 1.41 (1.16-1.72) and 1.85 (1.47 2.32). After adjustment for potential confounders, the relationship between small LDL or HDL particles and CHD was no longer significant, irrespective of the method. CONCLUSIONS: In this prospective population study, we found that the relationships between NMR-measured LDL and HDL sizes and CHD risk were slightly higher than those obtained with GGE. PMID- 20348401 TI - Graham Beastall. PMID- 20348402 TI - Effect of sialylated O-glycans in pro-brain natriuretic peptide stability. AB - BACKGROUND: Atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) are important in regulating a variety of cardiovascular and cellular functions. In cells, these peptides are made as proforms that are converted to mature forms. BNP and its related peptides are biomarkers for the diagnosis of heart failure. In this study, we examined glycosylation in pro-ANP, pro-BNP, and pro-CNP, which may alter their biochemical and metabolic properties. METHODS: Human pro-ANP, pro BNP, and pro-CNP were expressed in HEK 293 cells and murine HL-1 cardiomyocytes and analyzed by immunoprecipitation and Western blotting. We used deglycosylation enzymes to determine the carbohydrate content on these peptides and examined the effects of inhibiting O-glycosylation on cellular expression and stability of the peptides. RESULTS: In HEK 293 and HL-1 cells, pro-BNP, but not pro-ANP and pro CNP, from the culture medium had a greater molecular mass than that from cell lysate. Digestion with PNGase F, O-glycosidase, and sialidase A indicated that pro-BNP contained O-glycans but not N-glycans. The O-glycans on pro-BNP had sialic acids at their termini, protecting it from O-glycosidase digestion. In contrast, pro-ANP and pro-CNP contained no detectable amounts of N- or O-glycans. Inhibition of O-glycosylation on pro-BNP did not prevent its expression in the cells. However, partially O-glycosylated pro-BNP was much less stable than fully O- glycosylated pro-BNP. CONCLUSIONS: O-glycosylation is not necessary for pro BNP expression but important for its stability. PMID- 20348403 TI - Quantification of galactose-1-phosphate uridyltransferase enzyme activity by liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: The diagnosis of galactosemia usually involves the measurement of galactose-1-phosphate uridyltransferase (GALT) activity. Traditional radioactive and fluorescent GALT assays are nonspecific, laborious, and/or lack sufficient analytical sensitivity. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay for GALT enzyme activity measurement. METHOD: Our assay used stable isotope-labeled alpha- galactose-1-phosphate ([(13)C(6)] Gal-1-P) as an enzyme substrate. Sample cleanup and separation were achieved by reversed-phase ion-pair chromatography, and the enzymatic product, isotope labeled uridine diphosphate galactose ([(13)C(6)]-UDPGal), was detected by MS/MS at mass transition (571 > 323) and quantified by use of [(13)C(6)]-Glu-1-P (265 > 79) as an internal standard. RESULTS: The method yielded a mean (SD) GALT enzyme activity of 23.8 (3.8) mumol x (g Hgb)(-1) x h(-1) in erythrocyte extracts from 71 controls. The limit of quantification was 0.04 micromol x (g Hgb)(-1) x h(-1) (0.2% of normal control value). Intraassay imprecision was determined at 4 different levels (100%, 25%, 5%, and 0.2% of the normal control values), and the CVs were calculated to be 2.1%, 2.5%, 4.6%, and 9.7%, respectively (n = 3). Interassay imprecision CVs were 4.5%, 6.7%, 8.2%, and 13.2% (n = 5), respectively. The assay recoveries at the 4 levels were higher than 90%. The apparent K(m) of the 2 substrates, Gal-1-P and UDPGlc, were determined to be 0.38 mmol/L and 0.071 mmol/L, respectively. The assay in erythrocytes of 33 patients with classical galactosemia revealed no detectable activity. CONCLUSIONS: This LC MS/MS-based assay for GALT enzyme activity will be useful for the diagnosis and study of biochemically heterogeneous patients with galactosemia, especially those with uncommon genotypes and detectable but low residual activities. PMID- 20348404 TI - Diagnostic value of the hemopexin N-glycan profile in hepatocellular carcinoma patients. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common and rapidly fatal cancer. Current diagnostic methods for HCC have poor sensitivity and specificity, are invasive, and carry risk for complications. Newer markers are needed to overcome these problems and allow diagnosis of HCC at an earlier stage. In view of known associations between glycosylation changes and liver disease, we focused on the serum glycoprotein hemopexin and the specific characteristics of this liver synthesized glycoprotein. METHODS: We studied 49 healthy volunteers and 81 patients divided into the categories of fibrosis, cirrhosis, and HCC with cirrhosis. Hemopexin was purified from study participants' serum by use of heme agarose beads. The hemopexin N-glycan profile was determined by use of the DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis technique. RESULTS: We found that branching alpha-1,3-fucosylated multiantennary glycans on hemopexin were increased in the HCC group compared with the cirrhosis without HCC, fibrosis, and healthy volunteer groups, whereas nonmodified biantennary glycans decreased progressively across groups from fibrosis to the cirrhosis and HCC groups. Summarization of this information in a new marker, called the hemopexin glycan marker, enabled distinction of patients with HCC and cirrhosis from healthy volunteers and patients with fibrosis or cirrhosis with a sensitivity and specificity of 79% and 93%, respectively. CONCLUSIONS: This study demonstrated hemopexin to be a model protein for studying liver-specific N glycosylation. The hemopexin glycan marker could be a valuable complementary test to alpha-fetoprotein measurements for detection of HCC in patients with cirrhosis. Additional study of its utility for diagnosis and follow-up is recommended. PMID- 20348405 TI - The D-lemma: to screen or not to screen for 25-hydroxyvitamin D concentrations. PMID- 20348406 TI - Gamma' fibrinogen: evaluation of a new assay for study of associations with cardiovascular disease. AB - BACKGROUND: Studies of disease associations with gamma' fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay. METHODS: We developed an immunometric technique to measure gamma' fibrinogen concentrations in plasma and studied the clinical utility of this test in samples from healthy individuals enrolled in the Framingham Offspring Study and in a separate case/control study of coronary artery disease (CAD). Monoclonal antibody 2.G2.H9, specific for the unique carboxyl terminal peptide of the fibrinogen gamma' chain, was used as capture antibody. Sheep antihuman fibrinogen/horseradish peroxidase conjugate was used for detection, with 3,3',5,5'-tetramethylbenzidine as substrate. We evaluated the linearity, imprecision, analytical specificity, and lower limit of quantification of the assay. We determined the reference interval for gamma' fibrinogen in healthy individuals from the Framingham Offspring Study (n = 2879) and quantified associations between gamma' fibrinogen and cardiovascular disease risk factors. The sensitivity and specificity of gamma' fibrinogen in evaluating CAD patients (n = 133) was determined with ROC curve analysis. RESULTS: The gamma' fibrinogen ELISA had within-run CVs of 13.4% at 0.127 g/L and 4.8% at 0.416 g/L. The limit of quantification at an imprecision of 20% was 0.10 g/L. The reference interval for healthy individuals was 0.088-0.551 g/L. ROC curve analysis of results from patients with CAD yielded an area under the curve of 0.76, with a diagnostic accuracy of 0.78 at a decision threshold of 0.30 g/L. CONCLUSIONS: gamma' Fibrinogen shows excellent utility for cardiovascular risk analysis. PMID- 20348407 TI - High glucose upregulates C-reactive protein synthesis in macrophages. PMID- 20348408 TI - Nipple aspirate fluid proteome of healthy females and patients with breast cancer. AB - BACKGROUND: The ductal/alveolar system of the female breast constantly secretes and reabsorbs fluid in nonpregnant/nonlactating women. This fluid, referred to as nipple aspirate fluid (NAF), can be obtained by a noninvasive procedure and it is part of the microenvironment where more than 95% of breast cancers arise. METHODS: Using an Orbitrap mass analyzer coupled to a linear ion trap, we performed an in-depth proteomic analysis of NAF samples obtained from 3 healthy individuals and 3 patients with breast cancer. Multiple fractionation methods such as size-exclusion and anion-exchange chromatography were applied for protein separation before mass spectrometric analysis. RESULTS: We identified more than 800 unique proteins in total, generating the most extensive NAF proteome thus far. Using gene ontology, we classified the identified proteins by their subcellular localization and found that more than 50% were extracellular or plasma membrane proteins. By searching against the Plasma Proteome Database, we confirmed that 40% of the proteins were also found in the plasma. Unigene database searching for transcripts of the proteins not found in the plasma revealed that the vast majority were expressed in the mammary gland. CONCLUSIONS: Our extensive proteome database for NAF may be helpful in the identification of novel cancer biomarkers. PMID- 20348409 TI - Establishment of outcome-related analytic performance goals. AB - BACKGROUND: Accrediting organizations require laboratories to establish analytic performance criteria that ensure their tests provide results of the high quality required for patient care. However, the procedures for instituting performance criteria that are directly linked to the needs of medical practice are not well established, and therefore alternative strategies often are used to create and implement surrogate performance standards. CONTENT: We reviewed 6 approaches for establishing outcome-related analytic performance goals: (a) limits defined by regulations and external assessment programs, (b) limits based on biologic variation, (c) limits based on surveys of clinicians about their needs, (d) limits based on effects on guideline driven medical decisions, (e) limits based on analysis of patterns for ordering follow-up clinical tests, and (f) limits based on formal medical decision models. Performance criteria were tabulated for 12 common chemistry analytes and 4 routine hematology tests. CONCLUSIONS: There is no consensus currently about the preferred methods for establishing medically necessary analytic performance limits. The various methods reviewed give considerably different performance limits. The analytic performance limits claimed by a laboratory should correspond to those limits that can be reliably maintained based on validated QC monitoring systems. These limits generally are larger than the observed CVs and bias parameters collected for assay validation. There is a major need for increased communication among laboratorians and clinicians on this topic, especially when the analytic performance limits that can be consistently maintained by a laboratory are inconsistent with the expectations of health care providers. PMID- 20348410 TI - Accident or arson: is CO-oximetry reliable for carboxyhemoglobin measurement postmortem? PMID- 20348411 TI - Commentary. PMID- 20348412 TI - Commentary. PMID- 20348415 TI - Plk4 is required for cytokinesis and maintenance of chromosomal stability. AB - Aneuploidy is a characteristic feature of established cancers and can promote tumor development. Aneuploidy may arise directly, through unequal distribution of chromosomes into daughter cells, or indirectly, through a tetraploid intermediate. The polo family kinase Plk4/Sak is required for late mitotic progression and is haploinsufficient for tumor suppression in mice. Here we show that loss of heterozygosity (LOH) occurs at the Plk4 locus in 50% of human hepatocellular carcinomas (HCC) and is present even in preneoplastic cirrhotic liver nodules. LOH at Plk4 is associated with reduced Plk4 expression in HCC tumors but not with mutations in the remaining allele. Plk4(+/-) murine embryonic fibroblasts (MEFs) at early passage show a high incidence of multinucleation, supernumerary centrosomes, and a near-tetraploid karyotype. Underlying these phenotypes is a high rate of primary cytokinesis failure, associated with aberrant actomyosin ring formation, reduced RhoA activation, and failure to localize the RhoA guanine nucleotide exchange factor Ect2 to the spindle midbody. We further show that Plk4 normally localizes to the midbody and binds to and phosphorylates Ect2 in vitro. With serial passaging Plk4(+/-) MEFs rapidly immortalize, acquiring an increasing burden of nonclonal and clonal gross chromosomal irregularities, and form tumors in vivo. Our results indicate that haploid levels of Plk4 disrupt RhoGTPase function during cytokinesis, resulting in aneuploidy and tumorigenesis, thus implicating early LOH at Plk4 as one of the drivers of human hepatocellular carcinogenesis. These findings represent an advance in our understanding of genetic predisposition to HCC, which continues to increase in incidence globally and particularly in North America. PMID- 20348416 TI - Af9/Mllt3 interferes with Tbr1 expression through epigenetic modification of histone H3K79 during development of the cerebral cortex. AB - Mutations of leukemia-associated AF9/MLLT3 are implicated in neurodevelopmental diseases, such as epilepsy and ataxia, but little is known about how AF9 influences brain development and function. Analyses of mouse mutants revealed that during cortical development, AF9 is involved in the maintenance of TBR2 positive progenitors (intermediate precursor cells, IPCs) in the subventricular zone and prevents premature cell cycle exit of IPCs. Furthermore, in postmitotic neurons of the developing cortical plate, AF9 is implicated in the formation of the six-layered cerebral cortex by suppressing a TBR1-positive cell fate mainly in upper layer neurons. We show that the molecular mechanism of TBR1 suppression is based on the interaction of AF9 with DOT1L, a protein that mediates transcriptional control through methylation of histone H3 lysine 79 (H3K79). AF9 associates with the transcriptional start site of Tbr1, mediates H3K79 dimethylation of the Tbr1 gene, and interferes with the presence of RNA polymerase II at the Tbr1 transcriptional start site. AF9 expression favors cytoplasmic localization of TBR1 and its association with mitochondria. Increased expression of TBR1 in Af9 mutants is associated with increased levels of TBR1 regulated expression of NMDAR subunit Nr1. Thus, this study identified AF9 as a developmental active epigenetic modifier during the generation of cortical projection neurons. PMID- 20348417 TI - Staircase tableaux, the asymmetric exclusion process, and Askey-Wilson polynomials. AB - We introduce some combinatorial objects called staircase tableaux, which have cardinality 4(n)n!, and connect them to both the asymmetric exclusion process (ASEP) and Askey-Wilson polynomials. The ASEP is a model from statistical mechanics introduced in the late 1960s, which describes a system of interacting particles hopping left and right on a one-dimensional lattice of n sites with open boundaries. It has been cited as a model for traffic flow and translation in protein synthesis. In its most general form, particles may enter and exit at the left with probabilities alpha and gamma, and they may exit and enter at the right with probabilities beta and delta. In the bulk, the probability of hopping left is q times the probability of hopping right. Our first result is a formula for the stationary distribution of the ASEP with all parameters general, in terms of staircase tableaux. Our second result is a formula for the moments of (the weight function of) Askey-Wilson polynomials, also in terms of staircase tableaux. Since the 1980s there has been a great deal of work giving combinatorial formulas for moments of classical orthogonal polynomials (e.g. Hermite, Charlier, Laguerre); among these polynomials, the Askey-Wilson polynomials are the most important, because they are at the top of the hierarchy of classical orthogonal polynomials. PMID- 20348418 TI - Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists. AB - The C-terminal segment of the human insulin receptor alpha-chain (designated alphaCT) is critical to insulin binding as has been previously demonstrated by alanine scanning mutagenesis and photo-cross-linking. To date no information regarding the structure of this segment within the receptor has been available. We employ here the technique of thermal-factor sharpening to enhance the interpretability of the electron-density maps associated with the earlier crystal structure of the human insulin receptor ectodomain. The alphaCT segment is now resolved as being engaged with the central beta-sheet of the first leucine-rich repeat (L1) domain of the receptor. The segment is alpha-helical in conformation and extends 11 residues N-terminal of the classical alphaCT segment boundary originally defined by peptide mapping. This tandem structural element (alphaCT L1) thus defines the intact primary insulin-binding surface of the apo-receptor. The structure, together with isothermal titration calorimetry data of mutant alphaCT peptides binding to an insulin minireceptor, leads to the conclusion that putative "insulin-mimetic" peptides in the literature act at least in part as mimics of the alphaCT segment as well as of insulin. Photo-cross-linking by novel bifunctional insulin derivatives demonstrates that the interaction of insulin with the alphaCT segment and the L1 domain occurs in trans, i.e., these components of the primary binding site are contributed by alternate alpha-chains within the insulin receptor homodimer. The tandem structural element defines a new target for the design of insulin agonists for the treatment of diabetes mellitus. PMID- 20348419 TI - Identification, recombinant expression, and characterization of the 100 kDa high molecular weight Hymenoptera venom allergens Api m 5 and Ves v 3. AB - Insect stings can cause life-threatening IgE-mediated anaphylactic reactions in venom-allergic patients. Although several compounds have already been described as venom allergens, prominent allergen candidates especially in the higher m.w. range have still remained elusive. Tandem mass spectrometry-based sequencing assigned a candidate gene to the most prominent putative high m.w. allergen Api m 5 (allergen C) in honeybee (Apis mellifera) venom and also allowed identification of its homologue Ves v 3 in yellow jacket (Vespula vulgaris) venom. Both proteins exhibit a pronounced sequence identity to human dipeptidyl peptidase IV or CD26. Reactivity of a human IgE mAb verified the presence of these proteins in the venoms. Both proteins were produced in insect cells and characterized for their enzymatic activity as well as their allergenic potential using sera and basophils from insect venom-allergic patients. Both Api m 5 and Ves v 3 were recognized by specific IgE of the majority of patients even in the absence of cross-reactive carbohydrate determinants. Serologic IgE reactivity closely matched activation of human basophils by Api m 5 or Ves v 3, thus underlining their relevance in functional assays. With Api m 5 and Ves v 3, a new pair of homologous allergens becomes available for future clinical applications in diagnosis and therapy that may also contribute to the understanding of molecular mechanisms of insect venoms. Moreover, the patient IgE reactivity together with the cellular activation demonstrates for the first time the relevance of high m.w. allergens in the context of hymenoptera venom allergy. PMID- 20348420 TI - Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury. AB - Sepsis and septic acute lung injury are among the leading causes for morbidity and mortality of critical illness. Extracellular adenosine is a signaling molecule implicated in the cellular adaptation to hypoxia, ischemia, or inflammation. Therefore, we pursued the role of the A2B adenosine receptor (AR) as potential therapeutic target in endotoxin-induced acute lung injury. We gained initial insight from in vitro studies of cultured endothelia or epithelia exposed to inflammatory mediators showing time-dependent induction of the A2BAR (up to 12.9 + or - 3.4-fold, p < 0.05). Similarly, murine studies of endotoxin-induced lung injury identified an almost 4.6-fold induction of A2BAR transcript and corresponding protein induction with LPS exposure. Studies utilizing A2BAR promoter constructs and RNA protection assays indicated that A2BAR induction involved mRNA stability. Functional studies of LPS-induced lung injury revealed that pharmacological inhibition or genetic deletion of the A2BAR was associated with dramatic increases in lung inflammation and histologic tissue injury. Studies of A2BAR bone marrow chimeric mice suggested pulmonary A2BAR signaling in lung protection. Finally, studies with a specific A2BAR agonist (BAY 60-6583) demonstrated attenuation of lung inflammation and pulmonary edema in wild-type but not in gene-targeted mice for the A2BAR. These studies suggest the A2BAR as potential therapeutic target in the treatment of endotoxin-induced forms of acute lung injury. PMID- 20348421 TI - Induction of TGF-beta 1, not regulatory T cells, impairs antiviral immunity in the lung following bone marrow transplant. AB - Patients receiving hematopoietic stem cell transplantation or bone marrow transplantation (BMT) as therapy for various malignancies or autoimmune diseases have an increased risk for infectious complications posttransplant, especially in the lung. We have used BMT in mice and murine gammaherpesvirus, gammaHV-68, to study the efficacy of adaptive immune responses post-BMT. Five weeks posttransplant, mice have fully reconstituted their hematopoietic lineages in both the lung and periphery. When challenged with virus, however, BMT mice have a reduced ability to clear lytic virus from the lung. Defective viral control in BMT mice is not related to impaired leukocyte recruitment or defective APC function. Rather, BMT mice are characterized by defective CD4 cell proliferation, skewing of effector CD4 T cells from a Th1 to a Th17 phenotype, and an immunosuppressive lung environment at the time of infection that includes overexpression of TGF-beta1 and PGE(2) and increased numbers of regulatory T cells. Neither indomethacin treatment to block PG synthesis nor anti-CD25 depletion of regulatory T cells improved antiviral host defense post-BMT. Transplanting mice with transgenic bone marrow expressing a dominant-negative TGF betaRII under the permissive CD4 promoter created mice in which effector CD4 and CD8 cells were unresponsive to TGF-beta1. Mice with TGF-beta1-nonresponsive effector T cells had restored antiviral immunity and improved Th1 responses post BMT. Thus, our results indicate that overexpression of TGF-beta1 following myeloablative conditioning post-BMT results in impaired effector T cell responses to viral infection. PMID- 20348422 TI - Francisella acid phosphatases inactivate the NADPH oxidase in human phagocytes. AB - Francisella tularensis contains four putative acid phosphatases that are conserved in Francisella novicida. An F. novicida quadruple mutant (AcpA, AcpB, AcpC, and Hap [DeltaABCH]) is unable to escape the phagosome or survive in macrophages and is attenuated in the mouse model. We explored whether reduced survival of the DeltaABCH mutant within phagocytes is related to the oxidative response by human neutrophils and macrophages. F. novicida and F. tularensis subspecies failed to stimulate reactive oxygen species production in the phagocytes, whereas the F. novicida DeltaABCH strain stimulated a significant level of reactive oxygen species. The DeltaABCH mutant, but not the wild-type strain, strongly colocalized with p47(phox) and replicated in phagocytes only in the presence of an NADPH oxidase inhibitor or within macrophages isolated from p47(phox) knockout mice. Finally, purified AcpA strongly dephosphorylated p47(phox) and p40(phox), but not p67(phox), in vitro. Thus, Francisella acid phosphatases play a major role in intramacrophage survival and virulence by regulating the generation of the oxidative burst in human phagocytes. PMID- 20348423 TI - Isoallergen variations contribute to the overall complexity of effector cell degranulation: effect mediated through differentiated IgE affinity. AB - Most allergens exist in several variants (isoallergens), each of which may be recognized differently by patient IgE. We have previously shown that several properties of the IgE repertoire, including IgE affinity and IgE clonality, are important factors determining degranulation responses of effector cells involved in type I allergic reactions. However, less is known about how the repertoire of naturally occurring isoallergens may affect this response. Thus, in this study, we investigated how individual rIgE Ab clones derived from a human subject are able to distinguish among variants of Der p 2 isoallergens and assessed the impact on basophil degranulation. Biacore analyses showed that individual rIgE clones cloned from an individual allergic to house dust mites recognized Der p 2 with binding affinities varying up to 100-fold between different Der p 2 isoforms. In a well-defined biological system consisting of human basophils sensitized with low rIgE clonality, degranulation responses were directly related to rIgE affinity toward particular rDer p 2 isoallergens. However, basophils sensitized with polyclonal patients' sera showed no differences in degranulation responses toward the different rDer p 2 isoallergens. In conclusion, our study shows that individual IgE Abs are able to bind single allergens with a broad range of affinities due to natural isoallergen variations, contributing further to the overall complexity of IgE-allergen interactions at the effector cell surface, which is, however, blurred by the polyclonal nature of patients' IgE repertoires. PMID- 20348424 TI - Central nervous system destruction mediated by glutamic acid decarboxylase specific CD4+ T cells. AB - High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. Although there is a considerable amount of data focusing on the role of GAD65-specific CD4(+) T cells in type 1 diabetes, little is known about their role in SPS. In this study, we show that mice possessing a monoclonal GAD65-specific CD4(+) T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. GAD65-reactive CD4(+) T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. In the presence of B cells, high titer anti-GAD65 autoantibodies were generated, but these had no effect on the incidence or severity of disease. In addition, GAD65-specific CD4(+) T cells isolated from the brain were activated and produced IFN-gamma. These findings suggest that GAD65-reactive CD4(+) T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65 mediated diseases of the CNS. PMID- 20348425 TI - Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide binding oligomerization domain-mediated NF-kappa B signaling. AB - Vibrio vulnificus and Vibrio cholerae are Gram-negative pathogens that cause serious infectious disease in humans. The beta form of pro-IL-1 is thought to be involved in inflammatory responses and disease development during infection with these pathogens, but the mechanism of beta form of pro-IL-1 production remains poorly defined. In this study, we demonstrate that infection of mouse macrophages with two pathogenic Vibrio triggers the activation of caspase-1 via the NLRP3 inflammasome. Activation of the NLRP3 inflammasome was mediated by hemolysins and multifunctional repeat-in-toxins produced by the pathogenic bacteria. NLRP3 activation in response to V. vulnificus infection required NF-kappaB activation, which was mediated via TLR signaling. V. cholerae-induced NLRP3 activation also required NF-kappaB activation but was independent of TLR stimulation. Studies with purified V. cholerae hemolysin revealed that toxin-stimulated NLRP3 activation was induced by TLR and nucleotide-binding oligomerization domain 1/2 ligand-mediated NF-kappaB activation. Our results identify the NLRP3 inflammasome as a sensor of Vibrio infections through the action of bacterial cytotoxins and differential activation of innate signaling pathways acting upstream of NF kappaB. PMID- 20348426 TI - Caspases in virus-infected cells contribute to recognition by CD8+ T lymphocytes. AB - CD8(+) cytotoxic T lymphocytes recognize infected cells in which MHC class I molecules present pathogen-derived peptides that have been processed mainly by proteasomes. Many infections induce a set of proteases, the caspases involved in apoptosis or inflammation. In this study, we report that processing and presentation of a short vaccinia virus-encoded Ag can take place also by a nonproteasomal pathway, which was blocked in infected cells with chemical inhibitors of caspases. By cleaving at noncanonical sites, at least two caspases generated antigenic peptides recognized by T lymphocytes. The sites and the peptidic products were partially overlapping but different to those used and produced by proteasomes in vitro. Antigenic natural peptides produced in infected cells by either pathway were quantitatively and qualitatively similar. Finally, coexpression of the natural vaccinia virus protein B13, which is an inhibitor of caspases and apoptosis, impaired Ag presentation by the caspase pathway in infected cells. These data support the hypothesis that numerous cellular proteolytic systems, including those induced during infection, such as caspases involved in apoptosis or in inflammation, contribute to the repertoire of presented peptides, thereby facilitating immunosurveillance. PMID- 20348427 TI - Human TLRs 10 and 1 share common mechanisms of innate immune sensing but not signaling. AB - TLRs are central receptors of the innate immune system that drive host inflammation and adaptive immune responses in response to invading microbes. Among human TLRs, TLR10 is the only family member without a defined agonist or function. Phylogenetic analysis reveals that TLR10 is most related to TLR1 and TLR6, both of which mediate immune responses to a variety of microbial and fungal components in cooperation with TLR2. The generation and analysis of chimeric receptors containing the extracellular recognition domain of TLR10 and the intracellular signaling domain of TLR1, revealed that TLR10 senses triacylated lipopeptides and a wide variety of other microbial-derived agonists shared by TLR1, but not TLR6. TLR10 requires TLR2 for innate immune recognition, and these receptors colocalize in the phagosome and physically interact in an agonist dependent fashion. Computational modeling and mutational analysis of TLR10 showed preservation of the essential TLR2 dimer interface and lipopeptide-binding channel found in TLR1. Coimmunoprecipitation experiments indicate that, similar to TLR2/1, TLR2/10 complexes recruit the proximal adaptor MyD88 to the activated receptor complex. However, TLR10, alone or in cooperation with TLR2, fails to activate typical TLR-induced signaling, including NF-kappaB-, IL-8-, or IFN-beta driven reporters. We conclude that human TLR10 cooperates with TLR2 in the sensing of microbes and fungi but possesses a signaling function distinct from that of other TLR2 subfamily members. PMID- 20348429 TI - Genomic and coexpression analyses predict multiple genes involved in triterpene saponin biosynthesis in Medicago truncatula. AB - Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones (sapogenins). Saponins possess many biological activities, including conferring potential health benefits for humans. However, most of the steps specific for the biosynthesis of triterpene saponins remain uncharacterized at the molecular level. Here, we use comprehensive gene expression clustering analysis to identify candidate genes involved in the elaboration, hydroxylation, and glycosylation of the triterpene skeleton in the model legume Medicago truncatula. Four candidate uridine diphosphate glycosyltransferases were expressed in Escherichia coli, one of which (UGT73F3) showed specificity for multiple sapogenins and was confirmed to glucosylate hederagenin at the C28 position. Genetic loss-of-function studies in M. truncatula confirmed the in vivo function of UGT73F3 in saponin biosynthesis. This report provides a basis for future studies to define genetically the roles of multiple cytochromes P450 and glycosyltransferases in triterpene saponin biosynthesis in Medicago. PMID- 20348430 TI - Alkylresorcinol synthases expressed in Sorghum bicolor root hairs play an essential role in the biosynthesis of the allelopathic benzoquinone sorgoleone. AB - Sorghum bicolor is considered to be an allelopathic crop species, producing phytotoxins such as the lipid benzoquinone sorgoleone, which likely accounts for many of the allelopathic properties of Sorghum spp. Current evidence suggests that sorgoleone biosynthesis occurs exclusively in root hair cells and involves the production of an alkylresorcinolic intermediate (5-[(Z,Z)-8',11',14' pentadecatrienyl]resorcinol) derived from an unusual 16:3Delta(9,12,15) fatty acyl-CoA starter unit. This led to the suggestion of the involvement of one or more alkylresorcinol synthases (ARSs), type III polyketide synthases (PKSs) that produce 5-alkylresorcinols using medium to long-chain fatty acyl-CoA starter units via iterative condensations with malonyl-CoA. In an effort to characterize the enzymes responsible for the biosynthesis of the pentadecyl resorcinol intermediate, a previously described expressed sequence tag database prepared from isolated S. bicolor (genotype BTx623) root hairs was first mined for all PKS like sequences. Quantitative real-time RT-PCR analyses revealed that three of these sequences were preferentially expressed in root hairs, two of which (designated ARS1 and ARS2) were found to encode ARS enzymes capable of accepting a variety of fatty acyl-CoA starter units in recombinant enzyme studies. Furthermore, RNA interference experiments directed against ARS1 and ARS2 resulted in the generation of multiple independent transformant events exhibiting dramatically reduced sorgoleone levels. Thus, both ARS1 and ARS2 are likely to participate in the biosynthesis of sorgoleone in planta. The sequences of ARS1 and ARS2 were also used to identify several rice (Oryza sativa) genes encoding ARSs, which are likely involved in the production of defense-related alkylresorcinols. PMID- 20348431 TI - The coiled-coil protein VIG1 is essential for tethering vacuoles to mitochondria during vacuole inheritance of Cyanidioschyzon merolae. AB - Vacuoles/lysosomes function in endocytosis and in storage and digestion of metabolites. These organelles are inherited by the daughter cells in eukaryotes. However, the mechanisms of this inheritance are poorly understood because the cells contain multiple vacuoles that behave randomly. The primitive red alga Cyanidioschyzon merolae has a minimum set of organelles. Here, we show that C. merolae contains about four vacuoles that are distributed equally between the daughter cells by binding to dividing mitochondria. Binding is mediated by VIG1, a 30-kD coiled-coil protein identified by microarray analyses and immunological assays. VIG1 appears on the surface of free vacuoles in the cytosol and then tethers the vacuoles to the mitochondria. The vacuoles are released from the mitochondrion in the daughter cells following VIG1 digestion. Suppression of VIG1 by antisense RNA disrupted the migration of vacuoles. Thus, VIG1 is essential for tethering vacuoles to mitochondria during vacuole inheritance in C. merolae. PMID- 20348432 TI - Innate immune responses activated in Arabidopsis roots by microbe-associated molecular patterns. AB - Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe associated molecular patterns (MAMPs). By monitoring transcriptional activation of beta-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen encoded mechanisms to block these MAMP-elicited signaling pathways. PMID- 20348433 TI - The Arabidopsis stem cell factor POLTERGEIST is membrane localized and phospholipid stimulated. AB - Stem cell maintenance and differentiation are tightly regulated in multicellular organisms. In plants, proper control of the stem cell populations is critical for extensive postembryonic organogenesis. The Arabidopsis thaliana protein phosphatase type 2C proteins POLTERGEIST (POL) and PLL1 are essential for maintenance of both the root and shoot stem cells. Specifically, POL and PLL1 are required for proper specification of key asymmetric cell divisions during stem cell initiation and maintenance. POL and PLL1 are known to be integral components of the CLE/WOX signaling pathways, but the location and mechanisms by which POL and PLL1 are regulated within these pathways are unclear. Here, we show that POL and PLL1 are dual-acylated plasma membrane proteins whose membrane localization is required for proper function. Furthermore, this localization places POL and PLL1 in proximity of the upstream plasma membrane receptors that regulate their activity. Additionally, we find that POL and PLL1 directly bind to multiple lipids and that POL is catalytically activated by phosphatidylinositol (4) phosphate [PI(4)P] in vitro. Based on these results, we propose that the upstream receptors in the CLE/WOX signaling pathways may function to either limit PI(4)P availability or antagonize PI(4)P stimulation of POL/PLL1. Significantly, the findings presented here suggest that phospholipids play an important role in promoting stem cell specification. PMID- 20348435 TI - Social vulnerability of alcoholics and patients with alcohol-related dementia: a view from Russia. PMID- 20348434 TI - Common genetic pathways regulate organ-specific infection-related development in the rice blast fungus. AB - Magnaporthe oryzae is the most important fungal pathogen of rice (Oryza sativa). Under laboratory conditions, it is able to colonize both aerial and underground plant organs using different mechanisms. Here, we characterize an infection related development in M. oryzae produced on hydrophilic polystyrene (PHIL-PS) and on roots. We show that fungal spores develop preinvasive hyphae (pre-IH) from hyphopodia (root penetration structures) or germ tubes and that pre-IH also enter root cells. Changes in fungal cell wall structure accompanying pre-IH are seen on both artificial and root surfaces. Using characterized mutants, we show that the PMK1 (for pathogenicity mitogen-activated protein kinase 1) pathway is required for pre-IH development. Twenty mutants with altered pre-IH differentiation on PHIL-PS identified from an insertional library of 2885 M. oryzae T-DNA transformants were found to be defective in pathogenicity. The phenotypic analysis of these mutants revealed that appressorium, hyphopodium, and pre-IH formation are genetically linked fungal developmental processes. We further characterized one of these mutants, M1373, which lacked the M. oryzae ortholog of exportin-5/Msn5p (EXP5). Mutants lacking EXP5 were much less virulent on roots, suggesting an important involvement of proteins and/or RNAs transported by EXP5 during M. oryzae root infection. PMID- 20348436 TI - Why is disulfiram superior to acamprosate in the routine clinical setting? A retrospective long-term study in 353 alcohol-dependent patients. AB - AIMS: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting. METHOD: Retrospective data from 2002 to 2007 were analysed on 353 alcohol dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating. RESULTS: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan-Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence. CONCLUSIONS: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence. PMID- 20348437 TI - Patterns of alcohol consumption in the Thai population: results of the National Household Survey of 2007. AB - AIMS: The National Household Survey for Substance and Alcohol Use is a periodic survey of the Thai population with the aim of estimating the number of people who use licit and illicit substances. This paper reports the findings regarding alcohol consumption from the 2007 survey. METHODS: A multistage sampling scheme was used. Provinces, districts, sub-districts, villages and households were randomly selected in sequence. All residents aged 12-65 years who had lived in their current household for >3 months were included. Altogether, 11,348 households and 26,633 respondents from 29 provinces were selected. A structured interview questionnaire, including information on pattern of alcohol consumption, Alcohol Use Disorder Identification Test (AUDIT) and consequences of drinking, was used. RESULTS: Of Thais aged 12-65 years, 63% were abstainers (men-40.9% and women-81.5%). The prevalence of current drinkers (defined as individuals who drank at least 10 g of alcohol in 12 months before the survey) was 28.6% (men 48.4% and women-12.7%). Based on the AUDIT score, 6.7% of the Thai population could be classified as hazardous drinkers, 0.9% as harmful drinkers and 0.6% as probable alcohol dependents. The median drinking intensity was 50.8 g in men and 25.4 g in women. After adjusting for other variables, predictors of being hazardous-harmful or probably dependent drinkers included male gender, age groups of 20-24 and 25-44 years, not married and living in Bangkok. CONCLUSION: The present study highlights the gender and age differences in drinking patterns and drinking consequences in Thailand. These issues should be taken into consideration when planning preventive measures to reduce alcohol consumption and related problems. PMID- 20348438 TI - Microvascular obstruction remains a portent of adverse remodeling in optimally treated patients with left ventricular systolic dysfunction after acute myocardial infarction. AB - BACKGROUND: Microvascular obstruction (MO) is associated with large acute myocardial infarction and lower left ventricular (LV) ejection fraction and predicts greater remodeling, but whether this effect is abolished by contemporary antiremodeling therapies is subject to debate. We examined the influence of several infarct characteristics, including MO, on LV remodeling in an optimally treated post-acute myocardial infarction cohort, using contrast-enhanced cardiac magnetic resonance. METHODS AND RESULTS: One hundred patients (mean age, 58.9+/ 12 years, 77%men) underwent contrast-enhanced cardiac magnetic resonance at baseline (approximately 4 days) and at 12 and 24 weeks. The effects on LV remodeling (ie, change in LV end-systolic volume index [DeltaLVESVi]) of infarct site, transmurality, endocardial extent, and the presence of early and late MO were analyzed. Mean baseline infarct volume index decreased from 34.0 (21.2) mL/m(2) to 20.9 (12.9) mL/m(2) at 24 weeks (P<0.001). Infarct site had no influence on remodeling, but greater baseline infarct transmurality (r=0.47, P<0.001) and endocardial extent (r=0.26, P<0.01) were associated with higher DeltaLVESVi. Early MO was seen in 69 patients (69%) and persisted as late MO in 56 patients (56%). Patients with late MO underwent significantly greater remodeling than those without MO (DeltaLVESVi, +4.1 [13.4] versus -7.0 [12.7] mL/m(2), respectively, P=0.001); those with early MO only displayed an intermediate DeltaLVESVi (-4.9 [13.0] mL/m(2)). Importantly, late MO was seen frequently despite optimal coronary blood flow having been restored at angiography. CONCLUSIONS: Late MO on predischarge contrast-enhanced cardiac magnetic resonance remains an ominous predictor of adverse LV remodeling despite powerful antiremodeling therapy and may be useful in the risk stratification of survivors of acute myocardial infarction. PMID- 20348439 TI - The role of prejudice and the need for closure in religious fundamentalism. AB - Religious fundamentalism has been consistently linked to prejudice toward a variety of outgroups. This article proposes that this is partially the case because fundamentalist ideology provides a sense of consistency and closure. Outgroups that challenge the epistemic certainty that fundamentalism provides are rejected in an effort to protect this certainty. Results from two studies, including one using a nationally representative sample, found that the need for closure was related to fundamentalism and partially mediated the relationship between fundamentalism and the derogation of lesbians and gays (Study 1) and value violators in general (Study 2). Furthermore, in Study 2, it was found that only some aspects of the need for closure explain the fundamentalism-prejudice relationship. Results are discussed in relation to past need for closure and ideology research as well as what this means for the study of fundamentalism. PMID- 20348440 TI - Mothers, domestic violence, and child protection. AB - This article explores the relationship between understandings of domestic violence and the child protection response drawing on material gathered in focus groups with workers who support mothers dealing with both domestic violence and child protection issues. The interviewees expressed concern that the dynamics of domestic violence are often misunderstood and inappropriately responded to by child protection workers. This article critically examines the interviewees' concerns and concludes that to properly protect children, it is crucial that child protection workers have a clear understanding of the dynamics of and issues related to domestic violence. PMID- 20348441 TI - Role of the C-terminal tail of SmpB in the early stage of trans-translation. AB - Trans-translation relieves a stalled translation on the bacterial ribosome by transfer-messenger RNA (tmRNA) with the help of SmpB, an essential cofactor of tmRNA. Here, we examined the role of the unstructured C-terminal tail of SmpB using an in vitro trans-translation system. It was found that truncation of the C terminal tail or substitution of tryptophan residue at 147 in the middle of the C terminal tail affected the activity in the early stage of trans-translation. Our investigations also revealed that the C-terminal tail is not required for the events until GTP is hydrolyzed by EF-Tu in complex with tmRNA-SmpB. A synthetic peptide corresponding to the C-terminal tail of SmpB inhibited peptidyl-transfer of alanyl-tmRNA and A-site binding of SmpB, but not GTP hydrolysis. These results suggest that the C-terminal tail has a role in the step of accommodation of alanyl-tmRNA-SmpB into the A-site. Directed hydroxyl radical probing indicated that tryptophan residue at 147 is located just downstream of the decoding center in the mRNA path when SmpB is in the A-site. PMID- 20348442 TI - Differential regulation of microRNA stability. AB - MicroRNAs (miRNAs) are endogenous single-stranded RNA molecules of about 21 nucleotides in length that are fundamental post-transcriptional regulators of gene expression. Although the transcriptional and processing events involved in the generation of miRNAs have been extensively studied, very little is known pertaining to components that regulate the stability of individual miRNAs. All RNAs have distinct inherent half-lives that dictate their level of accumulation and miRNAs would be expected to follow a similar principle. Here we demonstrate that although most miRNA appear to be stable, like mRNAs, miRNAs possess differential stability in human cells. In particular, we found that miR-382, a miRNA that contributes to HIV-1 provirus latency, is unstable in cells. To determine the region of miR-382 responsible for its rapid decay, we developed a cell-free system that recapitulated the observed cell-based-regulated miR-382 turnover. The system utilizes in vitro-processed mature miRNA derived from pre miRNA and follows the decay of the processed miRNA. Using this system, we demonstrate that instability of miR-382 is driven by sequences outside its seed region and required the 3' terminal seven nucleotides where mutations in this region increased the stability of the RNA. Moreover, the exosome 3'-5' exoribonuclease complex was identified as the primary nuclease involved in miR 382 decay with a more modest contribution by the Xrn1 and no detectable contribution by Xrn2. These studies provide evidence for an miRNA element essential for rapid miRNA decay and implicate the exosome in this process. The development of a biochemically amendable system to analyze the mechanism of differential miRNA stability provides an important step in efforts to regulate gene expression by modulating miRNA stability. PMID- 20348443 TI - Selection of RNA aptamers imported into yeast and human mitochondria. AB - In the yeast Saccharomyces cerevisiae, nuclear DNA-encoded is partially imported into mitochondria. We previously found that the synthetic transcripts of yeast tRNA(Lys) and a number of their mutant versions could be specifically internalized by isolated yeast and human mitochondria. The mitochondrial targeting of tRNA(Lys) in yeast was shown to depend on the cytosolic precursor of mitochondrial lysyl-tRNA synthetase and the glycolytic enzyme enolase. Here we applied the approach of in vitro selection (SELEX) to broaden the spectrum of importable tRNA-derived molecules. We found that RNAs selected for their import into isolated yeast mitochondria have lost the potential to acquire a classical tRNA-shape. Analysis of conformational rearrangements in the importable RNAs by in-gel fluorescence resonance energy transfer (FRET) approach permitted us to suggest that protein factor binding and subsequent import require formation of an alternative structure, different from a classic L-form tRNA model. We show that in the complex with targeting protein factor, enolase 2, tRK1 adopts a particular conformation characterized by bringing together the 3'-end and the TPsiC loop. This is a first evidence for implication of RNA secondary structure rearrangement in the mechanism of mitochondrial import selectivity. Based on these data, a set of small RNA molecules with significantly improved efficiency of import into yeast and human mitochondria was constructed, opening the possibility of creating a new mitochondrial vector system able to target therapeutic oligoribonucleotides into deficient human mitochondria. PMID- 20348444 TI - The presence of high-molecular-weight viral RNAs interferes with the detection of viral small RNAs. AB - Viral small interfering RNA (siRNA) accumulation in plants is reported to exhibit a strong strand polarity bias, with plus (+) strand siRNAs dominating over minus (-) strand populations. This is of particular interest, as siRNAs processed from double-stranded RNA would be expected to accumulate equivalent amounts of both species. Here, we show that, as reported, (-) strand viral siRNAs are detected at much lower levels than (+) strand-derived species using standard Northern hybridization approaches. However, when total RNA is spiked with in vitro transcribed antisense viral genomic RNA, (-) strand viral siRNAs are detected at increased levels equivalent to those of (+) strand siRNA. Our results suggest that (+) and (-) strand viral siRNAs accumulate to equivalent levels; however, a proportion of the (-) strand siRNAs are sequestered from the total detectable small RNA population during gel electrophoresis by hybridizing to the high molecular-weight sense strand viral genomic RNA. Our findings provide a plausible explanation for the observed strand bias of viral siRNA accumulation, and could have wider implications in the analysis of both viral and nonviral small RNA accumulation. PMID- 20348445 TI - Reduced seed region-based off-target activity with lentivirus-mediated RNAi. AB - Along with silencing intended target genes, transfected siRNAs regulate numerous unintended transcripts through a mechanism in which the equivalent of a microRNA like seed region in the siRNA recognizes complementary sequences in transcript 3' UTRs. Amelioration of this off-target silencing would lead to more accurate interpretation of RNA interference (RNAi) experiments and thus greatly enhance their value. We tested whether lentivirus-mediated delivery of shRNA is prone to the sequence-based off-target activity prevalent in siRNA experiments. We compared target gene silencing and overall impact on global gene expression caused by multiple sequences delivered as both transfected siRNAs and lentivirus vector-expressed shRNAs. At equivalent levels of target gene silencing, signatures induced by shRNAs were significantly smaller than those induced by cognate siRNAs and arose less frequently from seed region activity. Interestingly, the low level of seed region-based off-target activity exhibited by shRNAs resulted in down-regulation of transcripts that were largely distinct from those regulated by siRNAs. On the basis of these observations, we recommend lentivirus-mediated RNAi for pathway profiling experiments that measure whole genome transcriptional readouts as well as for large-scale screens when resources for extensive follow up are limited. PMID- 20348446 TI - Hypermutation induced by APOBEC-1 overexpression can be eliminated. AB - APOBEC-1 overexpression in liver has been shown to effectively reduce apoB-100 levels. However, nonspecific hypermutation and liver tumor formation potentially related to hypermutation in transgenic animals compromise its potential use for gene therapy. In studying apoB mRNA editing regulation, we found that the core editing auxiliary factor ACF dose-dependently increases APOBEC-1 nonspecific hypermutation and specific editing with variable site sensitivity. Overexpression of APOBEC-1 together with ACF in human hepatic HepG2 cells hypermutated apoB mRNAs 20%-65% at sites 6639, 6648, 6655, 6762, 6802, and 6845, in addition to the normal 90% editing at 6666. The hypermutation activity of APOBEC-1 was decreased to background levels by a single point APOBEC-1 mutation of P29F or E181Q, while 50% of wild-type control editing at the normal site was retained. The hypermutations on both apoB and novel APOBEC-1 target 1 (NAT1) mRNA were also decreased to background levels with P29F and E181Q mutants in rat liver primary culture cells. The loss of hypermutation with the mutants was associated with significantly decreased APOBEC-1/ACF interaction. These data suggest that nonspecific hypermutation induced by overexpressing APOBEC-1 can be virtually eliminated by site-specific mutation, while maintaining specific editing activity at the normal site, reopening the potential use of APOBEC-1 gene therapy for hyperlipidemia. PMID- 20348447 TI - Regulation of pre-mRNA splicing in Xenopus oocytes by targeted 2'-O-methylation. AB - The 2'-OH group of the branch point adenosine is a key moiety to initiate pre mRNA splicing. We use RNA-guided RNA modification to target the pre-mRNA branch point adenosine for 2'-O-methylation, with the aim of blocking pre-mRNA splicing in vertebrate cells. We show that, under certain conditions, injection of a branch point-specific artificial box C/D RNA into Xenopus oocytes effectively 2' O-methylates adenovirus pre-mRNA at the target nucleotide. However, 2'-O methylation at the authentic branch point activates a host of cryptic branch points, thus allowing splicing to continue. These cryptic sites are mapped, and mutated. Upon injection, pre-mRNA free of cryptic branch points fails to splice when the branch point-specific box C/D RNA is present. However, 2'-O-methylation at the branch point does not prevent pre-mRNA from being assembled into pre catalytic spliceosome-like complexes prior to the first chemical step of splicing. Our results demonstrate that RNA-guided pre-mRNA modification can occur in the nucleoplasm of vertebrate cells, thus offering a powerful tool for molecular biology research. PMID- 20348448 TI - Residues in SRP9/14 essential for elongation arrest activity of the signal recognition particle define a positively charged functional domain on one side of the protein. AB - The signal recognition particle (SRP) is a ubiquitous cytoplasmic ribonucleoprotein complex required for the cotranslational targeting of proteins to the endoplasmic reticulum (ER). In eukaryotes, SRP has to arrest the elongation of the nascent chains during targeting to ensure efficient translocation of the preprotein, and this function of SRP is dependent on SRP9/14. Here we present the results of a mutational study on the human protein h9/14 that identified and characterized regions and single residues essential for elongation arrest activity. Effects of the mutations were assessed both in cell free translation/translocation assays and in cultured mammalian cells. We identified two patches of basic amino acid residues that are essential for activity, whereas the internal loop of SRP14 was found to be dispensable. One patch of important basic residues comprises the previously identified basic pentapetide KRDKK, which can be substituted by four lysines without loss of function. The other patch includes three lysines in the solvent-accessible alpha2 of h9. All essential residues are located in proximity in SRP9/14 and their basic character suggests that they serve as a positively charged platform for interactions with ribosomal RNA. In addition, they can all be lysines consistent with the hypothesis that they recognize their target(s) via electrostatic contacts, most likely with the phosphate backbone, as opposed to contacts with specific bases. PMID- 20348450 TI - The forgotten burden of deep venous disease. PMID- 20348449 TI - Ecm1 is a new pre-ribosomal factor involved in pre-60S particle export. AB - In eukaryotes, ribosome biogenesis is a highly conserved process that starts in the nucleus and ends in the cytoplasm. In actively growing yeast cells, it is estimated that each nuclear pore complex (NPC) contributes to the export of about 25 pre-ribosomal particles per minute. Such an extremely active process requires several redundant export receptors for the pre-60S particles. Here, we report the identification of a novel pre-60S factor, Ecm1, which partially acts like Arx1 and becomes essential when the NPC function is affected. Ecm1 depletion, combined with the deletion of NPC components led to pre-60S retention in the nucleus. Functional links that we identified between Ecm1, 60S biogenesis, pre-60S export, and the NPC were correlated with physical interactions of Ecm1 with pre-60S particles and nucleoporins. These results support that Ecm1 is an additional factor involved in pre-60S export. While Ecm1 and Arx1 have redundant functions, overproduction of either one could not complement the absence of the other, whereas overproduction of Mex67 was able to partially restore the growth defect resulting from the absence of Ecm1 or Arx1. These data highlight the involvement of many factors acting together to export pre-60S particles. PMID- 20348451 TI - The treatment of varicose veins: an investigation of patient preferences and expectations. AB - OBJECTIVES: A number of modalities are now available for the treatment of varicose veins. The aim of the study was to investigate the factors considered important by patients when contemplating treatment of their varicose veins. METHODS: Consecutive new patients referred to a vascular surgery service were invited to complete a short anonymous questionnaire prior to their consultation. The questionnaire consisted of 13 multiple choice questions relating to symptoms, potential varicose vein treatments and patient knowledge of existing therapies. RESULTS: Of 111 patients, there were 83 complete responses (75%). Symptoms of pain or aching were reported as moderate or severe by 77/103 (75%) of patients and significantly limited the activities of 47/101 (47%). Although the majority (89/103 [86%]) of patients were aware of surgery, only 52/103 (51%) knew of the existence of endothermal ablation (either laser or radiofrequency) and only 23/103 (22%) were aware of foam sclerotherapy. Some 58/92 (63%) were in favour of local anaesthetic treatment. Most patients (74/103, 72%) felt inadequately informed to express a preference regarding treatment type prior to their consultation, although 24/103 (23%) expressed a preference for endovenous treatment. Interestingly, 74/92 (80%) stated that the opinion of their vascular surgeon would be likely to or definitely influence their treatment decision and the majority of patients stated that what they had read in magazines (54/80, 64%) or on the Internet (51/85, 60%) would have no influence on their decision regarding treatment, respectively. CONCLUSION: Only a minority of patients referred with varicose veins were aware of endovenous treatments or felt adequately informed to express a treatment preference prior to consultation. Over half of patients expressed a preference for local anaesthetic therapy and a preference for a single visit treatment, although most would be strongly influenced by the opinion of their vascular surgeon and not influenced by media advertising. PMID- 20348452 TI - Calcium dobesilate and oxerutin: effectiveness of combination therapy. AB - OBJECTIVES: Chronic venous insufficiency (CVI) is an important cause of discomfort and inability to work. Hydroxyethylrutosides (Venoruton); 0-[beta hydroxyethyl]-rutosides) has been used for decades for the treatment of CVI. Studies have reported symptomatic relief and a decreased capillary filtration after the administration of the oral preparations. Calcium dobesilate is a synthetic venoactive drug acting on several levels. It inhibits capillary permeability; it has antioxidant properties; and it inhibits the synthesis of prostaglandins and thromboxanes, reducing platelet and erythrocyte aggregation, as well as blood viscosity. The aim of this study is to determine whether the combination of both drugs is more effective in decreasing patients' complaints. METHODS: One hundred and fifty patients with primary venous insufficiency were randomized into three groups: Group A receiving calcium dobesilate only, Group B receiving oxerutin only and Group C receiving both calcium dobesilate and oxerutin. Patients were evaluated with a questionnaire before and four weeks after treatment regarding following parameters: itching, fatigue, heaviness, numbness, cramp, swelling and sensitiveness. Patients rated their symptoms from 0 to 4 (0: absent; 1: mild; 2: moderate; 3: severe; 4: very severe). RESULTS: Complaints, which were scored by patients before and after treatment, decreased. Among the single-drug groups, itching score decreased more in Group B, whereas scores of fatigue, heaviness, numbness, cramp and swelling decreased more in Group A. But the difference was not significant, statistically. But all complaints decreased significantly in Group C. Difference of scores after treatment revealed no statistical significance in Group A and B, but scores of Group C produced a significant difference when compared with Group A and B. CONCLUSION: Results demonstrate that a combination of calcium dobesilate and oxerutin shows a better improvement of complaints. These observations have to be confirmed in larger series with objective tests. Changes of quality of life after a combination therapy might also be of interest. PMID- 20348453 TI - Current prescribing patterns of elastic compression stockings post-deep venous thrombosis. AB - OBJECTIVES: Post-thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT) characterized by chronic pain, swelling and heaviness, and may result in ulceration. Elastic compression stockings (ECS) worn daily after DVT appear to reduce the incidence and severity of PTS. The aims of our study were to investigate practices and perceptions of DVT patients and physicians regarding the use of ECS after DVT. METHODS: Two surveys were conducted. The first was sent to 225 staff and trainee clinicians and the second was administered to 150 DVT patients. RESULTS: The results demonstrated that the majority of senior staff (75%) believed that ECS were effective in preventing PTS and in managing venous symptoms. However, this was in contrast with junior trainees (21%) (P < 0.05). This resulted in only 63% of patients being prescribed ECS post-DVT. There was a lack of consensus as regards the optimal timing of initiation of ECS, duration of therapy and compression strength. Nearly all DVT patients who were prescribed ECS purchased them, 74% wore them daily, and most (61%) reported that ECS relieved swelling and symptoms. Physicians correctly predicted the main reasons for non compliance, but misjudged the scale of patient compliance with ECS. CONCLUSIONS: Our findings suggest that there is a lack of consensus among doctors regarding ECS use after DVT and widespread education regarding the latest evidence of the benefit of ECS after DVT. PMID- 20348454 TI - One-year outcomes of radiofrequency ablation of incompetent perforator veins using the radiofrequency stylet device. AB - OBJECTIVES: Early success treating incompetent perforator veins (IPVs) with radiofrequency ablation (RFA) and the trend to move varicose vein surgery into a walk-in walk-out service led to the design of a specific device enabling RFA of IPVs using local anaesthesia (ClosureRFS stylet). Our aim was to assess one-year outcomes of a clinical series of patients undergoing treatment with this device. Truncal reflux, where present, was treated initially, and RFA of IPVs was performed as a secondary procedure. METHOD: Duplex ultrasound examinations were performed and the presence of IPVs documented. Results were compared with preoperative scans. IPVs were classified as closed, not closed/reopened or de novo. RESULTS: Of the 75 patients invited for follow-up, 53 attended at a median time of 14 months (range 11-25). Sixty-seven limbs were analysed (M:F 1:2.1, median age 62, range 25-81). Of the 124 treated IPVs, 101 were closed (82%). Clinical, aetiological, anatomical and pathological clinical score was improved in 49.3% limbs. IPV closure was reduced in patients with recurrent varicose veins compared with primary varicose veins (72.3% versus 87%, P = 0.056). CONCLUSION: These results demonstrate the radiofrequency stylet device to be an effective treatment for IPVs. PMID- 20348455 TI - The use of prophylaxis in patients undergoing diagnostic tests for suspected venous thromboembolism. AB - OBJECTIVES: The purpose of this study was to describe the use of pharmacological and mechanical prophylaxis and clinical outcomes of patients undergoing diagnostic tests for suspected venous thromboembolism (VTE). METHODS: The medical records of 660 consecutive inpatients referred for suspected VTE at an academic medical centre were retrospectively reviewed. RESULTS: Acute VTE was diagnosed in 138 (21%) of the 660 patients; the incidence of deep vein thrombosis and pulmonary embolism was 18-25%, respectively. Only 61% of eligible patients received pharmacological prophylaxis and 43% of patients received mechanical prophylaxis. The incidence of VTE was higher in patients who did not receive pharmacological prophylaxis (30%) compared with patients who did (16%, P value <0.001). CONCLUSIONS: Preventive measures for VTE, including both pharmacological and mechanical prophylaxis, were underutilized in hospitalized patients undergoing diagnostic tests for suspected VTE. PMID- 20348456 TI - Use of durometry in assessment of venous disease. AB - OBJECTIVES: Ulceration of the lower limbs is a common debilitating complication of chronic venous hypertension. Detection of preulcerative skin changes would allow for identification of high-risk patients; early active treatment may prevent ulcer formation. METHODS: Patients with isolated venous disease and volunteers attending outpatient clinics underwent assessment of their clinical, aetiological, anatomical and pathological (CEAP) classification. We employed an industrial durometer, an instrument that measures the hardness of metals and plastic, to assess skin induration. The durometer probe was rested perpendicular on their skin 15 cm above the medial malleolus in non-ulcerated tissue, with the patient and limb in recumbency. The average of four measurements was derived. RESULTS: In 107 people, 203 lower limbs (mean age 55.6 years) were assessed. A significant difference in durometry readings was demonstrated between patients with CEAP classes 0, 1 and 2, and those with classes 4, 5 and 6 (P < 0.0005). There was statistically significant evidence that age and CEAP classification correlated with durometry (P < 0.0001). CONCLUSION: Durometry is of potential value in the assessment and monitoring of preulcerative venous disease, and could help to identify high-risk patients. This would assist in the institution of timely and appropriate treatment. PMID- 20348457 TI - Renal transplantation after excision of the inferior vena cava for residual renal cell carcinoma. AB - A rare case is reported of a 47-year-old patient who had residual tumour left in the stump of his left renal vein and inferior vena cava (IVC) after a left nephrectomy for renal cell carcinoma, having previously had a right nephrectomy for a non-malignant disease. He underwent delayed excision of the residual renal tumour after seven months with a prosthetic graft replacement of the IVC. Five years later he developed a graft infection caused by a graft-enteric duodenal fistula. The infected graft was excised and the duodenum closed. The patient has subsequently undergone a successful renal transplantation despite a lack of major venous outflow and remains alive and well eight years after initial removal of the tumour from the IVC. PMID- 20348458 TI - Effects of prd circadian clock mutations on FRQ-less rhythms in Neurospora. AB - Rhythmic conidiation (spore formation) in Neurospora crassa provides a model system for investigating the molecular mechanisms of circadian rhythmicity. A feedback loop involving the frq, wc-1, and wc-2 gene products (FRQ/ WCC) is an important component of the mechanism; however, rhythmic conidiation can still be observed when these gene products are absent. The nature of the oscillator(s) that drives this FRQ-less rhythmicity (FLO) is an important question in Neurospora circadian biology. We have looked for interactions between FRQ/WCC and FLO by assaying the effects on FRQ-less rhythms of mutations known to affect the period in the presence of FRQ. We assayed 4 prd mutations (prd-1, prd-2, prd-3, and prd-4) under 2 conditions in frq(null) strains: long-period free-running rhythms in chol-1 strains grown without choline, and heat-entrainable rhythms in choline-sufficient conditions. We found effects of all 4 mutations on both types of FRQ-less rhythms. The greatest effects were seen with prd-1 and prd-2, which abolished free-running rhythms in the chol-1; frq(10) backgrounds and significantly affected entrained peak timing under heat-entrainment conditions in frq( 10) backgrounds. The prd-3 and prd-4 mutations had more subtle effects on period and stability of free-running rhythms in the chol-1; frq(10) backgrounds and had little effect on peak timing under heat-entrainment conditions in frq(10) backgrounds. These results, along with previously published evidence for effects of prd mutations on other FRQ-less rhythms, suggest that either there are common components shared between the FRQ/WCC oscillator and several FRQ-less oscillators or that there is a single oscillator driving all conidiation rhythms. We favor a model of the Neurospora circadian system in which a single FRQ-less oscillator drives conidiation and interacts with the FRQ/WCC feedback loop; the output or amplitude of the FRQ-less oscillator can be affected by many gene products and metabolic conditions that reveal FRQ-less rhythmicity. We propose that prd-1 and prd-2 are good candidates for components of the FRQ-less oscillator and that prd 3 and prd-4 act on the system mainly through effects on FRQ/WCC. PMID- 20348459 TI - Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters. AB - In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters as compared to LD animals, 2) sex steroid treatment in SD-adapted male and female hamsters increased the number of Kiss1 neurons in the AVPV but decreased it in the ARC, 3) melatonin administration to LD-adapted hamsters decreased Kiss1 mRNA level in both the AVPV and the ARC in intact animals, whereas in castrated hamsters, melatonin rapidly inhibited Kiss1 expression in the ARC but not in the AVPV, and 4) pinealectomy of male or female SD-adapted hamsters increased the number of Kiss1 neurons in the ARC but not in the AVPV. In conclusion, our data demonstrate that Kiss1 expression in the Syrian hamster hypothalamus is down-regulated in SD via different mechanisms. In the ARC, melatonin inhibits Kiss1 via a direct effect on the hypothalamus, and this effect is probably sex steroid dependent, whereas in the AVPV, the decrease in Kiss1 expression appears to be secondary to the melatonin-driven reduction of sex steroid levels. Taken together, our data support the hypothesis that ARC Kiss1 neurons mediate melatonin effects on the gonadotropic axis of the Syrian hamster. PMID- 20348460 TI - Clock gene expression during chronic inflammation induced by infection with Trypanosoma brucei brucei in rats. AB - African sleeping sickness is characterized by alterations in rhythmic functions. It is not known if the disease affects the expression of clock genes, which are the molecular basis for rhythm generation. We used a chronic rat model of experimental sleeping sickness, caused by the extracellular parasite Trypanosoma brucei brucei (Tb brucei), to study the effects on clock gene expression. In tissue explants of pituitary glands from Period1-luciferase (Per1-luc) transgenic rats infected with Tb brucei, the period of Per1-luc expression was significantly shorter. In explants containing the suprachiasmatic nuclei (SCN), the Per1-luc rhythms were flat in 21% of the tissues. We also examined the relative expression of Per1, Clock, and Bmal1 mRNA in the SCN, pineal gland, and spleen from control and infected rats using qPCR. Both Clock and Bmal1 mRNA expression was reduced in the pineal gland and spleen following Tb brucei infection. Infected rats were periodic both in core body temperature and in locomotor activity; however, early after infection, we observed a significant decline in the amplitude of the locomotor activity rhythm. In addition, both activity and body temperature rhythms exhibited decreased regularity and "robustness." In conclusion, although experimental trypanosome infection has previously been shown to cause functional disturbances in SCN neurons, only 21% of the SCN explants had disturbed Per1-luc rhythms. However, our data show that the infection overall alters molecular clock function in peripheral clocks including the pituitary gland, pineal gland, and spleen. PMID- 20348461 TI - Time-dependent effects of dim light at night on re-entrainment and masking of hamster activity rhythms. AB - Bright light has been established as the most ubiquitous environmental cue that entrains circadian timing systems under natural conditions. Light equivalent in intensity to moonlight (<1 lux), however, also strongly modulates circadian function in a number of entrainment paradigms. For example, compared to completely dark nights, dim nighttime illumination accelerated re-entrainment of hamster activity rhythms to 4-hour phase advances and delays of an otherwise standard laboratory photocycle. The purpose of this study was to determine if a sensitive period existed in the night during which dim illumination had a robust influence on speed of re-entrainment. Male Siberian hamsters were either exposed to dim light throughout the night, for half of the night, or not at all. Compared to dark nights, dim illumination throughout the entire night decreased by 29% the time for the midpoint of the active phase to re-entrain to a 4-hour phase advance and by 26% for a 4-hour delay. Acceleration of advances and delays were also achieved with 5 hours of dim light per night, but effects depended on whether dim light was present in the first half, second half, or first and last quarters of the night. Both during phase shifting and steady-state entrainment, partially lit nights also produced strong positive and negative masking effects, as well as entrainment aftereffects in constant darkness. Thus, even in the presence of a strong zeitgeber, light that might be encountered under a natural nighttime sky potently modulates the circadian timing system of hamsters. PMID- 20348463 TI - In vivo quantification of the retinal reflectance spectral composition in elderly subjects before and after cataract surgery: Implications for the non-visual effects of light. AB - Light is the signal that entrains the biological clock in humans to the 24-hour external time. Recently, it has been shown that short wavelengths play a key role in this process. In the present study, we describe a procedure to measure, objectively and in a quick way, the spectral composition of the light reaching the retina in vivo. The instruments involved are the foveal reflection analyzer (FRA) and the macular pigment reflectometer (MPR). By making use of these reflectometers, we show quantitatively that in subjects with cataracts, the light input is especially reduced in the short wavelength range. After cataract surgery during which the crystalline lens is replaced by a transparent artificial lens, the transmittance of the short wavelengths (between 420-500 nm) improved on average by a factor of 4. We conclude that this technique holds great promises for the chronobiological field because it allows for quantification of the spectral composition and light levels reaching the retina in vivo. PMID- 20348462 TI - Light exposure patterns in healthy older and young adults. AB - Aging is associated with an earlier timing of circadian rhythms and a shorter phase angle between wake time and the timing of melatonin secretion or the core body temperature nadir. Light has a phase-dependent effect on the circadian pacemaker, and modifications of habitual light exposure in older people could contribute to a change in the timing of circadian rhythms or in the phase angle of entrainment. In this study, we compare natural light exposure of community dwelling older and young subjects studied at the same time of year, focusing on the pattern of light exposure across the waking day. We recorded light exposure data for 3 to 8 days from 22 older (aged 66.01 +/- 5.83) and 22 young subjects (aged 23.41 +/- 4.57), living at home on self-selected sleepwake schedules, and matched for time of year. All subjects were from New England (latitude 42.3 degrees N to 43 degrees N). We compared the percentage of the waking day spent by older and young subjects at 4 different light levels (from very dim to very bright). We compared hourly averaged light exposure data in each group according to clock time and with respect to each subject's daily sleepwake times. Although both age groups spent more than half of their waking hours in dim or moderate room light intensity (<100 lux), we found that the older subjects spent a significantly greater percentage of their waking day in the brighter light levels (> or =1000 lux); their hourly averaged light exposure levels were also significantly greater whether we examined the data with respect to absolute clock time, to wake time, or to bed time, and this was true across all seasons. We found that healthy older people were exposed to significantly higher levels of light throughout their waking day than young people. Differences in natural light exposure may contribute to the age-related phase advance of the circadian pacemaker and its later timing relative to the sleepwake cycle. This hypothesis should be explored further in carefully designed prospective studies. PMID- 20348464 TI - Nuclear receptor rev-erb-{alpha} circadian gene variants and lithium carbonate prophylaxis in bipolar affective disorder. AB - Rev-erb-alpha is one of the key components of the mammalian circadian mechanism; recently, it was also reported to be involved in the biological action of lithium. We investigated whether polymorphisms in the Rev-erb- alpha gene are associated with the long-term efficacy of lithium carbonate therapy in bipolar affective disorder. Seven single nucleotide polymorphisms (SNPs) were genotyped in a well-characterized sample of patients from Sardinia, Italy, who were followed prospectively for up to 27 years. Genotypic and allelic analysis did not show evidence for association between the polymorphisms and the different levels of lithium response. Further analyses grouping the different levels of response demonstrated that when the patients were separated into groups of nonresponders versus individuals who have had at least a minor or modest improvement in frequency of episodes or admissions, there was a significant increase in the frequency of the T allele in the nonresponder group (p = 0.0008). Logistic regression analyses showed that patients carrying at least one copy of the T allele for the rs2314339 marker were shown to be approximately 3.5 times more likely to have no improvement or even a worsening of the illness (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.18-10.76). The results of this study may help to identify potential biological markers that can serve to predict the response of bipolar affective disorder patients to treatment, improving treatment efficacy. PMID- 20348465 TI - Velocity response curves support the role of continuous entrainment in circadian clocks. AB - Circadian clocks drive endogenous oscillations in organisms across the tree of life. The Earth's daily light/dark cycle entrains these clocks to the environment. Two major theories of light entrainment have been presented in the literature. The discrete theory emphasizes the instantaneous phase-shifting behavior of short pulses of light, and the continuous theory emphasizes changes to the period of oscillations in constant-light conditions. Historically, the primary tool for predicting and understanding discrete entrainment has been the PRC, which measures discrete adjustments to the clock's phase. The authors present a unified theory, which relies on a velocity response curve (VRC), similar in shape to a PRC, but that describes continuous adjustments to the clock's speed. The VRC explains data from both discrete and continuous light experiments and is therefore an invaluable tool to understand entrainment. The authors relate VRC features to specific entrainment behaviors, such as seasonal adjustments to the phase of entrainment. Furthermore, they estimate a VRC from PRC data and successfully reproduce additional PRC data. Finally, they entrain a VRC-based model to natural light/dark cycles, demonstrating the unified theory's ability to predict clock behavior in the face of a fluctuating signal. The results indicate that a VRC-based model not only provides a comprehensive understanding of entrainment but also has excellent predictive capabilities. PMID- 20348466 TI - Significant losses due to fasciolosis in Scottish sheep flocks. PMID- 20348467 TI - Strengthening cooperation on vectorborne diseases in Europe. PMID- 20348468 TI - Veterinary surgeons and suicide: a structured review of possible influences on increased risk. AB - Veterinary surgeons are known to be at a higher risk of suicide compared with the general population. There has been much speculation regarding possible mechanisms underlying the increased suicide risk in the profession, but little empirical research. A computerised search of published literature on the suicide risk and influences on suicide among veterinarians, with comparison to the risk and influences in other occupational groups and in the general population, was used to develop a structured review. Veterinary surgeons have a proportional mortality ratio (PMR) for suicide approximately four times that of the general population and around twice that of other healthcare professions. A complex interaction of possible mechanisms may occur across the course of a veterinary career to increase the risk of suicide. Possible factors include the characteristics of individuals entering the profession, negative effects during undergraduate training, work-related stressors, ready access to and knowledge of means, stigma associated with mental illness, professional and social isolation, and alcohol or drug misuse (mainly prescription drugs to which the profession has ready access). Contextual effects such as attitudes to death and euthanasia, formed through the profession's routine involvement with euthanasia of companion animals and slaughter of farm animals, and suicide 'contagion' due to direct or indirect exposure to suicide of peers within this small profession are other possible influences. PMID- 20348469 TI - Effects of plastic bits on the condition and behaviour of captive-reared pheasants. AB - Between 2005 and 2007, data were collected from game farms across England and Wales to examine the effects of the use of bits on the physiological condition and behaviour of pheasants. On each site, two pheasant pens kept in the same conditions were randomly allocated to either use bits or not. The behaviour and physiological conditions of pheasants in each treatment pen were assessed on the day of bitting and weekly thereafter until release. Detailed records of feed usage, medications and mortality were also kept. Bits halved the number of acts of bird-on-bird pecking, but they doubled the incidence of headshaking and scratching. Bits caused nostril inflammation and bill deformities in some birds, particularly after seven weeks of age. In all weeks after bitting, feather condition was poorer in non-bitted pheasants than in those fitted with bits. Less than 3 per cent of bitted birds had damaged skin, but in the non-bitted pens this figure increased over time to 23 per cent four weeks later. Feed use and mortality did not differ between bitted and non-bitted birds. PMID- 20348470 TI - Mycobacterium avium subspecies paratuberculosis in free-living amoebae isolated from fields not used for grazing. PMID- 20348474 TI - Uniting research into human and animal health. PMID- 20348475 TI - Case-control study on bleeding calf syndrome. PMID- 20348476 TI - Cutaneous mast cell tumours in dogs. PMID- 20348478 TI - Taenia serialis in a domestic rabbit. PMID- 20348479 TI - Systematic review of human-directed dog aggression. PMID- 20348480 TI - Parasites in chelonians. PMID- 20348481 TI - Future of veterinary physiotherapy. PMID- 20348482 TI - Transcriptomes and proteomes of dental follicle cells. AB - Ectomesenchymal dental stem cells could be feasible tools for dental tissue engineering. Dental follicle cells are a promising example, since they are capable of differentiation into various dental tissue cells, such as osteoblasts or cementoblasts. However, cellular mechanisms of cell proliferation and differentiation are not understood in detail. Basic knowledge of these molecular processes may shorten the time before ectomesenchymal dental stem cells can be exploited for bone augmentation in regenerative medicine. Recent developments in proteomics and transcriptomics have made information about genome-wide expression profiles accessible, which can aid in clarifying molecular mechanisms of cells. This review describes the transcriptomes and proteomes of dental follicle cells before and after differentiation, and compares them with differentially expressed populations from dental tissue or bone marrow. PMID- 20348483 TI - Changes in bone mineral and matrix in response to a soft diet. AB - Alterations in the magnitude of habitual mechanical loads upon the skeleton may not only affect bone architecture, but also influence the nature of the bone matrix. We tested the hypothesis that changing the mechanical consistency of the diet affects both the mineral and non-mineralized moieties of bone matrix. Female rats were fed a soft diet (powdered chow as a paste), while control animals were fed the standard chow. After 8 or 20 wks, animals were killed. Cranial (mandible, maxilla, parietal, and frontal) bones and ulnae were analyzed for mineralization density by quantitative backscattered electron microscopy, and sulphated glycosaminoglycan levels with alcian blue staining were measured by microdensitometry. The soft diet group showed a significant increase in mineralization density distribution at almost all cranial sites and a reduction in alcian blue staining in alveolar bone. Altering the consistency of the diet significantly affects mineral concentration and glycosaminoglycan content of alveolar bone. PMID- 20348484 TI - Transcriptome remodeling in hypoxic inflammation. AB - Hypoxia is an integral component of the inflamed tissue microenvironment. Today, the influence of hypoxia on the natural evolution of inflammatory responses is widely accepted; however, many molecular and cellular mechanisms mediating this relationship remain to be clarified. Hypoxic stress affects several independent transcriptional regulators related to inflammation in which HIF-1 and NF-kappaB play central roles. Transcription factors interact with both HATs and HDACs, which are components of large multiprotein co-regulatory complexes. This review summarizes the current knowledge on hypoxia-responsive transcriptional pathways in inflammation and their importance in the etiology of chronic inflammatory diseases, with the primary focus on transcriptional co-regulators and histone modifications in defining gene-specific transcriptional responses in hypoxia, and on the recent progress in the understanding of hypoxia-mediated epigenetic reprogramming. Furthermore, this review discusses the molecular cross-talk between glucocorticoid anti-inflammatory pathways and hypoxia. PMID- 20348485 TI - Scientific ideas on muguet (thrush) in the XVIII century. PMID- 20348486 TI - Can fiber posts increase root stresses and reduce fracture? AB - The clinical success of fiber posts has been attributed to their lower elastic modulus. The tested hypothesis was that fiber posts could lead to lower risk of post debonding and lower risk of root fracture, despite an increase in root stresses. Stress analyses were carried out with a 3D finite element model of a premolar restored with a metallic or a fiber post. Bonded and non-bonded post/cement interface conditions were simulated. We calculated risk-of-fracture indices by determining the highest principal stress values divided by the tensile strength. Shear stresses along the post/cement interface were analyzed for the bonded models. Compared with the premolar restored with a metallic post, the fiber post generated lower stresses along the interface and higher stresses in the root. However, with the fiber post, fracture was less likely to occur in the root, since its core and post fracture indices were higher. PMID- 20348488 TI - Retrospective study of spontaneous osteosarcomas in the nonobese diabetic strain and nonobese diabetic-derived substrains of mice. AB - In this retrospective study, spontaneous osteosarcomas were found in 85 of 1,202 (7.1%) nonobese diabetic (NOD) and NOD-derived mice. Gross tumors were evident at an average age of 155.8 days in male mice and 151.4 days in female mice. Compared with male mice, female mice had a statistically insignificant higher incidence: 56 cases (8.3% of 672) versus 28 cases (6.1% of 458). NOD/ShiLtJ mice had the highest incidence, with 39 cases among all the strains and substrains represented (3.2% of 1,202 necropsies), whereas NOD.SCID substrains had the highest incidence, with 16 cases among the various NOD-derived substrains (1.3% of 1,202 necropsies). There was a statistically significant difference in tumor incidence between NOD/ShiLtJ and NOD.SCID mice. Tumors were more frequent in the appendicular skeleton (55.7%) than in the axial skeleton (44.3%) and most often arose from the femurs. Histologically, osteoblastic osteosarcoma was the most common tumor type, with 79 cases (94%), followed by mixed osteosarcoma, with 5 cases (6%). Metastases were rare, with only 2 cases (2.3%). PMID- 20348487 TI - Doxycycline effects on serum bone biomarkers in post-menopausal women. AB - We previously demonstrated that subantimicrobial-dose-doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs. PMID- 20348489 TI - Diagnostic exercise: generalized alopecia and mural folliculitis in a goat. AB - An 18-month-old cross-bred goat was presented with generalized erythema and thinning of the hair coat, as well as localized moderate scaling. Histopathological evaluation of skin biopsies showed hyperplasia and marked disruption of the infundibular epithelium owing to a predominant infiltrate of macrophages with multinucleated histiocytic giant cells and some lymphocytes, plasma cells, and eosinophils. Examination of peripheral blood and skin by polymerase chain reaction gave positive results for ovine herpesvirus type 2 consistent with a diagnosis of malignant catarrhal fever. PMID- 20348490 TI - Angiostrongylus cantonensis: lesions in brain and spinal cord. PMID- 20348491 TI - Hepatic visceral larva migrans of Toxocara canis. PMID- 20348492 TI - Emergence of new alleles of the MSP-3alpha gene in Plasmodium vivax isolates from Korea. AB - Nucleotide sequence analysis of the Plasmodium vivax PvMSP-3alpha gene was conducted on blood from 143 malaria patients admitted to Korea University Medical Center from 1996 to 2007 in the Republic of Korea (ROK). From 1996 to 2002, the PvMSP-3alpha alleles were of two types, SKOR-67 (2.53 kb) and SKOR-69 (1.78 kb), which differed in length and amino acid sequence. Two new variants with similar size to SKOR-67 were first observed in 2002 and in 2006-2007 accounted for nearly 50% (25/51) of the sampled isolates. The new variants had the same amino acid sequence as SKOR-69 in the N-terminal region, but in Blocks I and II and in the C terminal region, they were similar to previously reported isolates from Thailand, Papua New Guinea, India, Brazil, and Ecuador strains. PMID- 20348493 TI - Syndromic diagnosis of malaria in rural Sierra Leone and proposed additions to the national integrated management of childhood illness guidelines for fever. AB - Many countries in Africa, including Sierra Leone, have adopted artemisinin-based combination therapy as first-line therapy for treatment of patients with malaria. Because laboratory testing is often unavailable in rural areas, the cost-benefit and viability of this approach may depend on accurately diagnosing malaria by using clinical criteria. We assessed the accuracy of syndromic diagnosis for malaria in three peripheral health units in rural Sierra Leone and determined factors that were associated with an accurate malaria diagnosis. Of 175 children diagnosed with malaria on syndromic grounds, 143 (82%) were confirmed by the Paracheck-Pf test. In a multivariate analysis, splenomegaly (P = 0.04) was the only clinical sign significantly associated with laboratory-confirmed malaria, and sleeping under a bed net was protective (P = 0.05). Our findings show that clinical malaria is diagnosed relatively accurately in rural Sierra Leone. Incorporating bed net use and splenomegaly into the national Integrated Management of Childhood Illness guidelines for evaluation of fever may further enhance diagnostic accuracy for malaria. PMID- 20348494 TI - Treatment with coartem (artemether-lumefantrine) in Papua New Guinea. AB - A recent drug efficacy trial reported Coartem (artemether-lumefantrine) to be highly effective against Plasmodium falciparum in children less than 5 years of age in Papua New Guinea (PNG). In contrast, we have observed high levels of treatment failures in non-trial conditions in a longitudinal cohort study in the same age group in PNG. Recrudescences were confirmed by genotyping of three different marker genes to provide optimal discrimination power between parasite clones. After excluding genetic host factors by genotyping potentially relevant cytochrome P450 loci, the high number of treatment failures in our study is best explained by poor adherence to complex dosing regimens in combination with insufficient fat supplementation, which are both crucial parameters for the outcome of Coartem treatment. In contrast to the situation in classic drug trials with ideal treatment conditions, our field survey highlights potential problems with unsupervised usage of Coartem in routine clinical practice and under program conditions. PMID- 20348495 TI - Transmission and cross-mating of high-level resistance Plasmodium falciparum dihydrofolate reductase haplotypes in The Gambia. AB - A high-level pyrimethamine resistance Plasmodium falciparum lineage with triple dihydrofolate reductase (dhfr) mutations prevails across Africa. However, additional minority lineages were seen. We examined transmission success of mutant dhfr haplotypes among 22 children in The Gambia and 60 infected Anopheles gambiae mosquitoes fed on their blood. Additional polymorphic genes of the gametocyte-specific protein (pfg377) and merozoite surface protein-1 (MSP-1) were examined. Similarities were seen between pfg377 and MSP-1 alleles in children and mosquitoes and evidence of cross-mating between different parasite genotypes was seen in some infected mosquitoes, reflecting high transmission success of existing clones. With regard to dhfr, 16 haplotypes were seen among the children: 2 carried double mutations and 14 carried triple mutations. However, only nine haplotypes, all with triple mutations, were detected among mosquitoes. A single triple-mutant dhfr haplotype, similar to that in other countries in Africa, predominated among children (42%) and mosquitoes (60%), supporting the hypothesis of migration of this haplotype across Africa. However, evidence of cross-mating between the above haplotypes signifies the role of local evolution. PMID- 20348496 TI - A comparison of two short-course primaquine regimens for the treatment and radical cure of Plasmodium vivax malaria in Thailand. AB - Thai adult males (N = 85) with acute Plasmodium vivax malaria and normal glucose 6-phosphate dehydrogenase screening were randomized to receive 30 mg or 60 mg primaquine daily for 7 days (N = 43 and 42, respectively). The regimens were well tolerated and all patients recovered fully. Median fever clearance (47 hours; range 4 to 130 hours), mean + or - SD parasite clearance times (87.7 + or - 25.3 hours), gametocyte clearance, and adverse effects were similar in the 2 groups. Two patients, 1 from each group, had a 30% reduction in hematocrit. The cumulative 28 day relapse rate (95% confidence interval) by Kaplan Meier survival analysis was 29% (16-49%) in the 30 mg group compared with 7% (2-24%) in the 60 mg group; P = 0.027. Comparison with previous data obtained at this same site suggests that the recurrences comprised approximately 17% recrudescences and 12% relapses in the 30 mg/day group compared with 3% recrudescences and 4% relapses in the 60 mg/day group. These data suggest that the dose-response relationships for primaquine's asexual stage and hypnozoitocidal activities in-vivo are different. A 1 week course of primaquine 60 mg daily is an effective treatment of vivax malaria in this region. PMID- 20348497 TI - TLR9 polymorphisms are associated with altered IFN-gamma levels in children with cerebral malaria. AB - Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at -1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at -1237 or the G allele at 1174 had higher levels of IFN-gamma than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-gamma levels in children with UM or altered TNF-alpha levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection. PMID- 20348498 TI - Malaria parasitemia and CD4 T cell count, viral load, and adverse HIV outcomes among HIV-infected pregnant women in Tanzania. AB - We examined the cross-sectional relationships between malaria parasitemia and CD4 T cell count and viral load among human immunodeficiency virus (HIV)-infected pregnant women. We then followed women to investigate whether or not baseline parasitemia predicted CD4 T cell counts or viral loads > 90 days post-baseline or predicted time to HIV disease stage 3 or 4 or acquired immune deficiency syndrome (AIDS)-related death (ARD). Parasitemia level was nonlinearly associated with viral load at baseline and among measurements taken > 90 days post-baseline; women with low baseline parasitemia, versus none, had higher viral loads at both time points. Any baseline parasitemia predicted an increased rate of ARD among women with baseline CD4 T cell counts > or = 500 cells/microL (ratio rate [RR] = 2.6; 95% confidence interval [CI] = 1.1-6.0; P test for heterogeneity = 0.05). Further study is warranted to determine whether or not parasitemia is especially detrimental to individuals with lower levels of immunosuppression or chronic low parasitemia. PMID- 20348499 TI - Severe congenital malaria acquired in utero. AB - Vertical transmission of Plasmodium falciparum is under-recognized and usually associated with asymptomatic low-level parasitemia at birth. We report symptomatic congenital malaria presenting as a neonatal sepsis syndrome. The presence at birth of a high asexual parasitemia, gametocytemia, and splenomegaly indicated in utero rather than intrapartum transmission. The neonate was successfully treated with intravenous artesunate followed by oral dihydroartemisinin-piperaquine, without apparent adverse effects. PMID- 20348500 TI - Spatio-temporal patterns in kdr frequency in permethrin and DDT resistant Anopheles gambiae s.s. from Uganda. AB - The planned upscaling of vector control strategies requires insight into the epidemiological consequences of vector resistance. Therefore, the pyrethroid and DDT resistance status of Anopheles gambiae s.l. was assessed in Uganda from 2004 to 2006, and spatial and seasonal variations in knockdown resistance (kdr) frequencies were analyzed in terms of epidemiological significance. Anopheles gambiae s.l. was DDT and pyrethroid resistant in central and eastern Uganda. The L1014S kdr allele frequencies varied from 3% to 48% in An. gambiae s.s. Although the homozygous resistant genotype was the most prevalent genotype among survivors, the genotypes could not entirely explain the bioassay results. In the dry season, the kdr frequency was significantly higher in Plasmodium falciparum infected mosquitoes, indicating that mosquitoes bearing a kdr mutation have a better adult survival, hence a higher likelihood of becoming infectious. This study showed that kdr might have an epidemiological impact that could jeopardize the vector control strategies. PMID- 20348501 TI - First report of widespread wild populations of Triatoma infestans (Reduviidae, Triatominae) in the valleys of La Paz, Bolivia. AB - Wild populations of Triatoma infestans, the main vector of Chagas disease in the Southern Cone countries, may be involved in reinfestation of human dwellings, limiting the success of vector-control campaigns in Bolivia. Knowledge of the distribution of these populations remains incomplete. We report here the detection of T. infestans wild populations in large areas in the department of La Paz, Bolivia. Among 18 sylvatic areas investigated, 17 were positive with T. infestans specimens. The infection rate of captured T. infestans with Trypanosoma cruzi was 85.7% in adult specimens. These results expand the geographical distribution of wild populations of T. infestans; it may be distributed throughout the Inter-Andean Dry Forest eco-region of Bolivia. The current information allows us to propose the hypothesis that a sylvatic origin of the reinfestation is located in the valleys of La Paz. PMID- 20348502 TI - Human trypanosomiasis in the eastern region of the Panama Province: new endemic areas for Chagas disease. AB - The epidemiology of Chagas disease was studied in five rural communities located in the eastern region of the Panama Province. Serological tests for Trypanosoma cruzi infection revealed a prevalence of 5.88% (12/204). Hemocultures coupled with polymerase chain reaction (PCR) analysis showed a Trypanosoma rangeli infection rate of 5.88% (12/204). An overall trypanosome infection index of 11.76% (24/204) was detected in this population. A total of 121 triatomine specimens were collected in domestic and peridomestic habitats. Rhodnius pallescens was confirmed as the predominant species. Molecular analysis showed that 17.8% (13/73) of the examined insects were positive for T. cruzi, 17.8% (13/73) for T. rangeli, and 35.6% (26/73) presented mixed infections. Among 73 R. pallescens evaluated, 16.4% (12/73) contained opossum blood meals. The epidemiological implications of these findings are discussed. PMID- 20348503 TI - Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. AB - American Trypanosomiasis or Chagas disease (CD) is a neglected disease that affects Latin American people worldwide. Two old antiparasitic drugs, benznidazole and nifurtimox, are currently used for specific CD treatment with limited efficacy in chronic infections and frequent side effects. New drugs are needed for patients with chronic CD as well as for immunosuppressed patients, for whom the risk of reactivation is life-threatening. We describe a case of chronic CD and systemic lupus erythematosus (SLE) that required immunosuppression to control the autoimmune process. It was found that benznidazole induced a reduction, but not an elimination, of circulating Trypanosoma cruzi levels, whereas subsequent treatment with posaconazole led to a successful resolution of the infection, despite the maintenance of immunosuppressive therapy. PMID- 20348504 TI - First cases of cutaneous leishmaniasis caused by Leishmania (Viannia) naiffi infection in Surinam. AB - Cutaneous leishmaniasis in Surinam is generally caused by infection by Leishmania guyanensis. We report three cases of infection with Leishmania (Viannia) naiffi, a Leishmania species not described from Surinam before. Treatment with pentamidine proved to be effective. PMID- 20348505 TI - Development of a reverse transcriptase loop-mediated isothermal amplification (LAMP) assay for the sensitive detection of Leishmania parasites in clinical samples. AB - Here we describe a generic, reverse transcriptase-loop-mediated isothermal amplification (RT-LAMP) assay, for the identification of Leishmania species from clinical samples. LAMP is an isothermal reaction recently developed as a point-of care diagnostic tool. Primers were designed in the conserved region of the 18S ribosomal RNA (rRNA) gene; amplification was visualized by the pre-amplification addition of fluorescent detection reagent (FDR) and a simple UV lamp. By using a reverse-transcriptase step, the system detected infections between 10 and 100 parasites per mL. The assay was tested on a range of nucleic acid extracts from Leishmania species, visceral leishmaniasis (VL) patients from Sudan, and cutaneous leishmaniasis (CL) patients from Suriname. The sensitivity of RT-LAMP from the blood of VL patients was 83% (N = 30) compared with microscopy of bone marrow and lymph-node aspirates; for CL patients the observed sensitivity was 98% (N = 43). The potential to use LAMP as a diagnostic tool for leishmaniasis is discussed. PMID- 20348506 TI - Leishmaniasis in the tongue of an immunocompetent man. AB - A 49-year-old immunocompetent white man had a painful ulcer (1.5 cm in diameter) on the left ventrolateral surface of a grossly enlarged tongue. The ulcer was present for two months. Impaired swallowing resulted in substantial weight loss and fatigue. Histopathologic analysis of a punch biopsy specimen indicated numerous Leishman Donovan bodies within macrophages. A polymerase chain reaction confirmed the presence of L. donovani. Therapy with two cycles of liposomal amphotericin B over a three-month period was administered. Four months after discharge, the ulcer had healed completely and the tongue returned to its normal size and function. PMID- 20348507 TI - Human CD8(+) T cells clear Cryptosporidium parvum from infected intestinal epithelial cells. AB - Intracellular protozoans of the genus Cryptosporidium are a major cause of diarrheal illness worldwide, especially in immunocompromised individuals. CD4(+) T cells and interferon-gamma are key factors in the control of cryptosporidiosis in human and murine models. Previous studies led us to hypothesize that CD8(+) T cells contribute to clearance of intestinal epithelial Cryptosporidium infection in humans. We report here that antigen expanded sensitized CD8(+) T cells reduce the parasite load in infected intestinal epithelial cell cultures and lyse infected intestinal epithelial cells. These effects are most likely mediated by the release of cytotoxic granules. Elimination of parasites seems to require antigen presentation through both human leukocyte antigen (HLA)-A and HLA-B. These data suggest that cytotoxic CD8(+) T cells play a role in clearing Cryptosporidium from the intestine, a previously unrecognized feature of the human immune response against this parasite. PMID- 20348508 TI - Identification of a high diversity of Cryptosporidium species genotypes and subtypes in a pediatric population in Nigeria. AB - A longitudinal study was conducted to determine the epidemiology of Cryptosporidium in 1,636 children in Nigeria. Oocyst prevalence ranged from 15.6% to 19.6% over one year. Cryptosporidium hominis (34), C. parvum (25), C. parvum/C. hominis (4), C. meleagridis (5), Cryptosporidium rabbit genotype (5), Cryptosporidium cervine genotype (3), and C. canis (1) were identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Glycoprotein 60 subgenotyping showed that 28 amplifiable C. hominis isolates consisted of 12 subtypes that belonged to 5 subtype families (Ia, Ib, Id, Ie, and 1 novel subtype family, Ih) and 23 amplifiable C. parvum isolates consisted of 6 subtypes that belonged to 4 subtype families (IIa, IIc, Iii, and IIm). Three C. meleagridis isolates sub-genotyped by sequence analysis of the small subunit ribosomal RNA gene fragment were type 1. This study is the first one to genetically characterize Cryptosporidium species and subtypes in Nigeria and highlights the presence of a high Cryptosporidium diversity in this pediatric population. PMID- 20348509 TI - A review of the clinical presentation of dientamoebiasis. AB - Among 750 symptomatic and asymptomatic patients, Dientamoeba fragilis was detected at a prevalence of 5.2% and more common than Giardia intestinalis. Most infected patients presented with diarrhea and abdominal pain with symptoms greater than 2 weeks duration being common. Bacterial and viral causes of infection were excluded by routine microbiological techniques. Treatment of D. fragilis infection with either iodoquinol, paromomycin, or combination therapy resulted in the eradication of the parasite and complete resolution of symptoms. Treatment failure/relapses were associated only with the use of metronidazole. Nineteen patients were examined for pin worm, no Enterobius vermicularis, a proposed vector of transmission, were detected. Intermittent shedding of D. fragilis was found to be highly variable. These studies confirm the pathogenic nature of D. fragilis and we recommend laboratories routinely test for the organism. PMID- 20348510 TI - Association between TNF-alpha and Entamoeba histolytica diarrhea. AB - An association between tumor necrosis factor alpha (TNF-alpha) and Entamoeba histolytica diarrhea was assessed in a cohort of 138 non-related Bangladeshi children who have been prospectively followed since 2001. Peripheral blood mononuclear cells (PBMCs) obtained at study entry were purified, cultured, and stimulated with soluble amebic antigen before cytokine measurement from supernatant. Higher levels of TNF-alpha were associated with increased risk of first (P = 0.01) and recurrent E. histolytica-related diarrheal episodes (P = 0.005). Children who developed E. histolytica diarrhea had significantly higher TNF-alpha protein levels than those who experienced asymptomatic E. histolytica infection (P value = 0.027) or no infection (P value = 0.017). Microarray studies performed using RNA isolated from acute and convalescent whole blood and colon biopsy samples revealed higher but non-significant TNF-alpha messenger RNA (mRNA) levels in subjects with acute E. histolytica diarrhea compared with convalescence. We conclude that there is an association between higher TNF-alpha production and E. histolytica diarrhea. PMID- 20348511 TI - Toxoplasma gondii seropositivity and co-infection with TORCH pathogens in high risk patients from Qatar. AB - Testing of patients who are deemed to be at high risk for TORCH pathogens, e.g., pregnant women, their fetuses, neonates, and acquired immunodeficiency syndrome (AIDS) patients, is important so that specific treatment can be initiated. This study included 1,857 such patients between 2005 and 2008. Logistic regression was used to evaluate factors associated with Toxoplasma gondii seropositivity. Among 823 women of childbearing age, 35.1% and 5.2% tested positive for T. gondii IgG and IgM, respectively. Three infants < or = 6 months of age (0.8% of 353) were congenitally infected. Factors associated with T. gondii IgG seropositivity included older age, East Mediterranean or African nationality, positive cytomegalovirus (CMV) and herpes simplex virus (HSV)-1 serostatus, and negative rubella IgG results. The decreasing prevalence of IgM antibodies between 2005 and 2008 suggested that exposure to T. gondii from food or environmental sources declined over this period in Qatar. Population-based studies of newborns would be helpful to accurately estimate incidence of congenital toxoplasmosis. PMID- 20348512 TI - Evaluating the efficacy of teaching methods regarding prevention of human epilepsy caused by Taenia solium neurocysticercosis in Western Kenya. AB - Taenia solium neurocysticercosis is a major cause of adult-onset epilepsy in developing countries. A questionnaire was administered to 282 Kenyan farmers, followed by a workshop, a second questionnaire, one-on-one training, and a third questionnaire. People who attended workshops were more likely to know how T. solium causes epilepsy in humans in the third visit than the second (P = 0.001). The likelihood that farmers would tether their pigs 100% of the time, limiting exposure to tapeworm eggs, increased after the first (P < 0.001) and second visits (P < 0.001). Farmers were more likely to have heard of Cysticercus cellulosae in the second (P = 0.001) and third visits (P = 0.007), and to know how pigs acquire infection in the second (P = 0.03) and third visits (P = 0.003). Farmers with at least a grade 8 education were more likely to know how T. solium is transmitted to humans in the second (P = 0.001) and third visits (P = 0.009), and were more likely to understand the relationship between epilepsy and T. solium in the second (P = 0.03) and third visits (P = 0.03). Grade 8 education may enhance learning from written material. Workshops followed by individual on farm training enhanced knowledge acquisition and behavior changes. Training local government extension workers contributed to the sustainability of this project. PMID- 20348513 TI - Emergence of sylvatic Echinococcus granulosus as a parasitic zoonosis of public health concern in an indigenous community in Canada. AB - Within a remote Canadian Indigenous community, at least 11* of people had antibodies against Echinococcus granulosus and E. granulosus eggs were detected in 6* of environmentally collected canine fecal samples. Dog ownership, hunting, and trapping were not risk factors for seropositivity, suggesting that people are most likely exposed to E. granulosus through indirect contact with dog feces in the environment. In this situation, human exposure could be most effectively curtailed by preventing consumption of cervid viscera by free-roaming dogs. PMID- 20348514 TI - High prevalence of Schistosoma japonicum infection in water buffaloes in the Philippines assessed by real-time polymerase chain reaction. AB - Difficulty in controlling human Schistosoma japonicum infection is partly attributed to the presence of non-human definitive hosts. Water buffaloes are a major reservoir for transmission of S. japonicum to humans in China. However, in the Philippines, reports based on microscopic examination of buffalo stool identified a low prevalence of S. japonicum, and mathematical models using these data concluded that water buffaloes are not a major reservoir for transmission of S. japonicum to humans. We collected stool from 81 buffaloes in Macanip, Leyte, the Philippines, and assayed for S. japonicum infection by the Danish Bilharziasis Laboratory technique, the Kato-Katz technique, miracidia hatching, and a highly validated real-time polymerase chain reaction. The prevalence defined by each assay was 3.7%, 3.7%, 0%, and 51.5% respectively. Our results demonstrate that microscopic-based techniques dramatically underestimate the prevalence of S. japonicum infection in water buffaloes in the Philippines and warrant reexamination of the role of bovines in transmission of S. japonicum to humans in the Philippines. PMID- 20348515 TI - Childhood malnutrition in Egypt using geoadditive Gaussian and latent variable models. AB - Major progress has been made over the last 30 years in reducing the prevalence of malnutrition amongst children less than 5 years of age in developing countries. However, approximately 27% of children under the age of 5 in these countries are still malnourished. This work focuses on the childhood malnutrition in one of the biggest developing countries, Egypt. This study examined the association between bio-demographic and socioeconomic determinants and the malnutrition problem in children less than 5 years of age using the 2003 Demographic and Health survey data for Egypt. In the first step, we use separate geoadditive Gaussian models with the continuous response variables stunting (height-for-age), underweight (weight-for-age), and wasting (weight-for-height) as indicators of nutritional status in our case study. In a second step, based on the results of the first step, we apply the geoadditive Gaussian latent variable model for continuous indicators in which the 3 measurements of the malnutrition status of children are assumed as indicators for the latent variable "nutritional status". PMID- 20348516 TI - Evaluation of the role of school children in the promotion of point-of-use water treatment and handwashing in schools and households--Nyanza Province, Western Kenya, 2007. AB - We installed drinking water and handwashing stations in 17 rural schools and trained teachers to promote water treatment and hygiene to pupils. We gave schools flocculent-disinfectant powder and hypochlorite solution for water treatment. We conducted a baseline water handling survey of pupils' parents from 17 schools and tested stored water for chlorine. We trained teachers and students about hygiene, installed water stations, and distributed instructional comic books to students. We conducted follow-up surveys and chlorine testing at 3 and 13 months. From baseline to 3-month follow-up, parental awareness of the flocculent-disinfectant increased (49-91%, P < 0.0001), awareness of hypochlorite remained high (93-92%), and household use of flocculent-disinfectant (1-7%, P < 0.0001) and hypochlorite (6-13%, P < 0.0001) increased, and were maintained after 13 months. Pupil absentee rates decreased after implementation by 26%. This school-based program resulted in pupil-to-parent knowledge transfer and significant increases in household water treatment practices that were sustained over 1 year. PMID- 20348517 TI - Evaluating delivery systems: complex evaluations and plausibility inference. AB - Delivery system evaluation is poorly defined and therefore a barrier to achieving increased coverage of interventions. We use a pre- and post-implementation cross sectional observational study with assessment of the intermediate processes to evaluate a new delivery system for insecticide-treated nets (ITNs) in two regions of Ghana. In Volta Region, ownership of at least one net rose from 38.3% to 45.4% (P = 0.06), and 6.5% of respondents used a voucher in the purchase. In Eastern Region, ownership of a net rose from 13.7% to 26.0% (P < 0.001) and 0.5% of households used a voucher to purchase a net. Just 40.7% and 21.1% of eligible antenatal clinic (ANC) attendees were offered a voucher in Volta and Eastern Regions, respectively, and 36.0% and 30.7% used their voucher in the purchase of an ITN. Without attributing nets to the specific delivery system, in Eastern Region the success of the new system would be overestimated. PMID- 20348518 TI - Antibody response from whole-cell pertussis vaccine immunized Brazilian children against different strains of Bordetella pertussis. AB - Bordetella pertussis is a gram-negative bacillus that causes the highly contagious disease known as pertussis or whooping cough. Antibody response in children may vary depending on the vaccination schedule and the product used. In this study, we have analyzed the antibody response of cellular pertussis vaccinated children against B. pertussis strains and their virulence factors, such as pertussis toxin, pertactin, and filamentous hemagglutinin. After the completion of the immunization process, according to the Brazilian vaccination program, children serum samples were collected at different periods of time, and tested for the presence of specific antibodies and antigenic cross-reactivity. Results obtained show that children immunized with three doses of the Brazilian whole-cell pertussis vaccine present high levels of serum antibodies capable of recognizing the majority of the components present in vaccinal and non-vaccinal B. pertussis strains and their virulence factors for at least 2 years after the completion of the immunization procedure. PMID- 20348519 TI - Epidemiology of spotted fever group and typhus group rickettsial infection in the Amazon basin of Peru. AB - A seroprevalence study for IgG antibodies against spotted fever group (SFGR) and typhus group (TGR) Rickettsia among humans and domestic pets was conducted in the city of Iquitos, located in the Amazon basin of Peru. Of 1,195 human sera analyzed, 521 (43.6%) and 123 (10.3%) were positive for SFGR and TGR antibodies, respectively. District of residence and participant age were associated with antibody positivity for both groups, whereas rodent sightings in the home were associated with TGR antibody positivity. Of the 71 canines tested, 42 (59.2%) were positive for SFGR antibodies, and two (2.8%) were positive for TGR antibodies; one active SFGR infection was detected by polymerase chain reaction. An uncharacterized SFGR species was detected in 95.9% (71/74) of Ctenocephalides felis pools collected from domestic pets. These data suggest that rickettsial transmission is widespread in Iquitos. Rickettsia species should be further explored as potential causes of acute febrile illnesses in the region. PMID- 20348520 TI - A patient from Argentina infected with Rickettsia massiliae. AB - The first confirmed case of Rickettsia massiliae infection in the New World (Buenos Aires, Argentina) is described. To date, only two cases of human infection had been reported in Europe. The patient, a woman, had a fever, a palpable purpuric rash on the upper and lower extremities, and a skin lesion (eschar) on the right leg compatible with tache noire. When interviewed, she reported having had contact with dog ticks. After treatment with doxycycline for 12 days, her symptoms resolved. Rickettsia massiliae infection was diagnosed by molecular-based detection of the microorganism in a biopsy specimen of the eschar. PMID- 20348521 TI - Comparing the effectiveness of shared versus private latrines in preventing trachoma in rural Tanzania. AB - Sharing latrines is common in sub-Saharan Africa with anecdotal accounts suggesting a link between water-, sanitation-, and hygiene-related disease and poorly maintained communal latrines. This study examines this link by assessing the association between shared latrines compared with private latrines and risk of trachoma. In 2007, as part of a larger case-control study, we conducted a sub study on latrine sharing in 594 households (92 cases, 502 controls) in seven rural Tanzanian communities. Case households were defined by having a child with clinical signs of trachoma. Latrine use was associated with a decreased risk of trachoma and there was no difference in risk between households using shared compared with private latrines (adjusted odds ratio = 0.95 [95% confidence interval = 0.55-1.67]). This study emphasizes the need to promote latrine use, which can be facilitated through latrine sharing in resource scarce areas, for prevention of trachoma. PMID- 20348522 TI - Glycosylation of the West Nile Virus envelope protein increases in vivo and in vitro viral multiplication in birds. AB - Many West Nile (WN) virus isolates associated with significant outbreaks possess a glycosylation site on the envelope (E) protein. E-protein glycosylated variants of New York (NY) strains of WN virus are more neuroinvasive in mice than the non glycosylated variants. To determine how E protein glycosylation affects the interactions between WN virus and avian hosts, we inoculated young chicks with NY strains of WN virus containing either glycosylated or non-glycosylated variants of the E protein. The glycosylated variants were more virulent and had higher viremic levels than the non-glycosylated variants. The glycosylation status of the variant did not affect viral multiplication and dissemination in mosquitoes in vivo. Glycosylated variants showed more heat-stable propagation than non glycosylated variants in mammalian (BHK) and avian (QT6) cells but not in mosquito (C6/36) cells. Thus, E-protein glycosylation may be a requirement for efficient transmission of WN virus from avian hosts to mosquito vectors. PMID- 20348523 TI - Mosquitoes and mosquito-borne arboviruses in the Qinghai-Tibet Plateau--focused on the Qinghai area, China. AB - An investigation was conducted to identify the distribution of mosquitoes and mosquito-borne arboviruses in the Qinghai-Tibet Plateau, China from July to August in 2007. A total of 8,147 mosquitoes representing six species from three genera (Aedes, Culex, and Anopheles) were collected in three locations (Geermu city, altitude of 2,780 m; Xining city, 2,200 m; Minhe county, 1,700 m). Six virus isolates were obtained including Tahyna virus (TAHV), Liaoning virus, and Culex pipiens pallens Densovirus. A serosurvey showed immunoglobulin G antibodies by immunofluorescence assay (IFA) against TAHV in residents of all three locations. The IFA-positive human samples were confirmed by 90% plaque-reduction neutralization tests (PRNT(90)) against TAHV with titers ranging from 1:20 to 1:10,240. In addition, TAHV seropositive cows, sheep, and swine were found in these locations. This investigation represents the first isolation of TAHV from Ae. (Och.) detritus and the first evidence of TAHV infection in residents and livestock in the Qinghai-Tibet Plateau. PMID- 20348524 TI - Clinical assessment of self-reported acute flaccid paralysis in a population based setting in Guatemala. AB - Historically, poliovirus infection has been an important cause of acute flaccid paralysis (AFP) worldwide; however, successful elimination of wild-type poliovirus in much of the world has highlighted the importance of other causes of AFP. Despite the evolving etiology, AFP surveillance in most developing countries still focuses on poliovirus detection and fails to detect many AFP cases, particularly among adults. We assessed 41 subjects self-reporting symptoms suggestive of AFP during a population-based health survey in the Department of Santa Rosa, Guatemala. Thirty-five (85%) of the suspected cases were not hospitalized. Most subjects (37) did not have features consistent with AFP or had other diagnoses explaining weakness. We identified two adults who had not received medical attention for a clinical illness consistent with Guillain-Barre syndrome, the most important cause of non-poliovirus AFP. Usual surveillance methods for AFP, particularly in developing countries, may underestimate the true burden of non-poliovirus AFP. PMID- 20348525 TI - Identification of norovirus as the top enteric viruses detected in adult cases with acute gastroenteritis. AB - To elucidate the importance of the norovirus and other enteric viruses, and the difference of the genetic relatedness on norovirus between the outbreak and sporadic cases, a total of 557 stool samples, consisting of 503 sporadic cases and 54 samples of 4 outbreaks were collected and tested for norovirus and other enteric viruses in Beijing, China, July 2007-June 2008. The data showed norovirus, rotavirus, astrovirus, and sapovirus, were detected in 26.6%, 6.1%, 1.8%, and 0.5%, respectively. Norovirus was detected almost throughout the surveillance period, norovirus co-infecting with rotavirus, astrovirus, and sapovirus, respectively, were identified both in outbreak and the sporadic cases. GII.4/2006 was identified as the predominant strain circulating both in outbreak and sporadic cases. The results showed that norovirus was rather the important agent than other enteric viruses affected adults with acute gastroenteritis; no significant genetic relatedness of the dominant strains was found between the outbreak and sporadic cases. PMID- 20348526 TI - Assessing and maximizing the acceptability of global positioning system device use for studying the role of human movement in dengue virus transmission in Iquitos, Peru. AB - As use of global positioning system (GPS) technology to study disease transmission increases, it is important to assess possible barriers to its use from the perspective of potential study participants. Fifteen focus group discussions stratified by sex, age, and motherhood status were conducted in 2008 in Iquitos, Peru. All participants said they would accept using a GPS unit for study purposes for 2-4 weeks. Participants' main concerns included caring properly for the unit, whether the unit would audio/videotape them, health effects of prolonged use, responsibility for units, and confidentiality of information. A pilot study was then conducted in which 126 persons were asked to carry GPS units for 2-4 weeks; 98% provided consent. All persons used the units expressing minimal concerns, although 44% reported forgetting the device at least once. Our study is the first to highlight participant concerns related to use of GPS for long-term monitoring of individual behavior in a resource-limited setting. PMID- 20348527 TI - Characteristic of dengue disease in Taiwan: 2002-2007. AB - Taiwan's dengue outbreaks have a unique type of transmission: starting by import from abroad in early summer, spreading out locally, and ending in the winter. This pattern repeats every year. Most of the dengue patients are adults, with dengue fever peaking in the 50-54 year age range, and dengue hemorrhagic fever in the 60-64 year age range. Two patterns of dengue infection were found: DENV-2 in 2002 with 74% of secondary infection in contrast to non-DENV-2 (DENV-1 or DENV-3) in 2004-2007 with approximately 70% of primary infection. Secondary dengue virus infection increases disease morbidity, but not mortality in adults. The active serological surveillance shows two-thirds of the dengue-infected adults are symptomatic post infection. The Taiwanese experience of adult dengue should be valuable for countries or areas where, although dengue is not endemic, the Aedes aegypti vector exists and dengue virus can be introduced by travelers. PMID- 20348528 TI - A case of yellow fever vaccine-associated viscerotropic disease in Ecuador. AB - We report the first case of viscerotropic syndrome in Ecuador. Because of similarities between yellow fever and viscerotropic syndrome, the incidence of this recently described complication of vaccination with the 17D yellow fever vaccine is not known. There is a large population in South America that is considered at risk for possible reemergence of urban yellow fever. Knowledge of potentially fatal complications of yellow fever vaccine should temper decisions to vaccinate populations where the disease is not endemic. PMID- 20348529 TI - Novel swine-origin influenza A (H1N1) virus-associated hemophagocytic syndrome--a first case report. AB - Secondary or reactive hemophagocytic syndrome (HPS) is frequently related to viral infections. However, the novel swine-origin influenza A (H1N1) virus associated HPS has never been reported. On October 10, 2009, a 17-year-old female child with no past medical history, complaining of severe asthenia, pneumonia, myalgia, and high fever, was admitted to our department, and H1N1 DNA was detected. Five days after her hospitalization, all signs and symptoms aggravated into HPS. After treatment for H1N1 influenza, the patient had a recovery and clearance of H1N1 infection 10 days after hospitalization. Three weeks later, the patient was discharged without any complaints, indicating the etiological role of H1N1infection in HPS. PMID- 20348530 TI - A silent enzootic of an orthopoxvirus in Ghana, West Africa: evidence for multi species involvement in the absence of widespread human disease. AB - Human monkeypox has never been reported in Ghana, but rodents captured in forested areas of southern Ghana were the source of the monkeypox virus introduced into the United States in 2003. Subsequent to the outbreak in the United States, 204 animals were collected from two commercial trapping sites in Ghana. Animal tissues were examined for the presence of orthopoxvirus (OPXV) DNA using a real-time polymerase chain reaction, and sera were assayed for antibodies against OPXV. Animals from five genera (Cricetomys, Graphiurus, Funiscirus, and Heliosciurus) had antibodies against OPXV, and three genera (Cricetomys, Graphiurus, and Xerus) had evidence of OPXV DNA in tissues. Additionally, 172 persons living near the trapping sites were interviewed regarding risk factors for OPXV exposure, and their sera were analyzed. Fifty-three percent had IgG against OPXV; none had IgM. Our findings suggest that several species of forest dwelling rodents from Ghana are susceptible to naturally occurring OPXV infection, and that persons living near forests may have low-level or indirect exposure to OPXV-infected animals, possibly resulting in sub-clinical infections. PMID- 20348531 TI - Computational analysis of oxygen transport in a patient-specific model of abdominal aortic aneurysm with intraluminal thrombus. AB - Abdominal aortic aneurysm (AAA) is a degenerative disease in which the afflicted person suffers from a localised dilatation of the abdominal aorta. Intraluminal thrombus (ILT), which is present in approximately 75% of all AAAs, plays an important role in the progression of the disease. It has been suggested that ILT may attenuate oxygen diffusion to the aortic wall, resulting in further degeneration and weakening of the wall. Previous numerical studies using idealised AAA models have shown the effect of ILT thickness on oxygen diffusion, but patient-specific studies of oxygen transport incorporating convection, diffusion and reaction from the lumen to AAA wall are lacking. In the present study, a coupled fluid-thrombus-wall model was developed to simulate oxygen transport in a patient-specific AAA containing ILT. Blood flow in the lumen was governed by the Navier-Stokes equations and oxygen transfer was described by the convection-diffusion equation in the lumen, diffusion equation in the thrombus, and diffusion-reaction equation in the wall. A parametric study was performed to evaluate the sensitivity of numerical predictions to oxygen diffusivity in ILT and adventitial oxygen concentration. The results not only provide further support to previous findings that the presence of ILT may significantly impair oxygen transfer from blood to the aortic wall, but also demonstrate that adventitial oxygen concentration has a profound effect on oxygen concentration in the wall, and that the oxygen supply from the lumen to the wall can be reduced by 80% if the ILT thickness is greater than 5 mm. PMID- 20348532 TI - The effect of dynamic vessel motion on haemodynamic parameters in the right coronary artery: a combined MR and CFD study. AB - Human right coronary artery (RCA) haemodynamics is investigated using computational fluid dynamics (CFD) based on subject-specific information from magnetic resonance (MR) acquisitions. The dynamically varying vascular geometry is reconstructed from MR images, incorporated in CFD in conjunction with pulsatile flow conditions obtained from MR velocity mapping performed on the same subject. The effects of dynamic vessel motion on instantaneous and cycle-averaged haemodynamic parameters, such as wall shear stress (WSS), time-averaged WSS (TAWSS) and oscillatory shear index (OSI), are examined by comparing an RCA model with a time-varying geometry and those with a static geometry, corresponding to nine different time-points in the cardiac cycle. The results show that the TAWSS is similar for the dynamic and static wall models, both qualitatively and quantitatively (correlation coefficient 0.89-0.95). Conversely, the OSI shows much poorer correlations (correlation coefficient 0.38-0.60), with the best correspondence being observed with the static models constructed from images acquired in late diastole (at t = 0 and 800 ms, the cardiac cycle is 900 ms). These findings suggest that neglecting dynamic motion of the RCA is acceptable if TAWSS is the primary focus but may result in underestimation of haemodynamic parameters related to the oscillatory nature of the blood flow. PMID- 20348533 TI - Three-dimensional imaging and computational modelling for estimation of wall stresses in arteries. AB - The paper reviews techniques for the estimation of wall stresses in arterial disease. Wall stresses are important as arterial disease progresses through a complex interplay between local biology and local mechanical stresses. The possibility then arises of using wall stresses as new diagnostic indicators in patients with arterial disease. Estimation of wall stresses using imaging systems is problematic. Developments in the last 10 years have been aimed at providing tools for estimation of wall stresses within individual patients, using a combination of three-dimensional (3D) imaging and computational modelling. For blood flow, 3D arterial lumen information is obtained from 3D imaging. Computational fluid dynamics is then used to estimate the 3D velocity field within the lumen, from which wall shear stress may be calculated. For arterial mechanics, the 3D arterial wall geometry is integrated with solid modelling to provide estimates of the strain field and stress field within the artery wall. For intraplaque stresses, this has been achieved through the use of detailed two dimensional (2D) intraplaque geometry from MRI. Inverse techniques have been used to provide images of Young's modulus in atherosclerotic plaque using intravascular ultrasound and solid modelling. Several research centres now have processing chains to allow this technology to be used in clinical studies. In time, possibly over the next 10 years or so, robust protocols with proven clinical utility will arise which, when combined with high-performance computing, will allow image-guided modelling to be used as an adjunct to modern radiology in the same way that image-processing tools are used today. PMID- 20348534 TI - Analysis of haemodynamic factors involved in carotid atherosclerosis using computational fluid dynamics. AB - Atherosclerosis presents a massive healthcare burden in both the developing and developed world. There is mounting evidence relating to the involvement of haemodynamic factors in the pathogenesis of this process. This article aims to review the current understandings that have developed in this area, and to present a demonstrative case study obtained using state of the art computational fluid dynamics (CFD) methodology to model and analyse haemodynamic factors within the atheromatous carotid artery bifurcation. PMID- 20348535 TI - The mechanical triggers of plaque rupture: shear stress vs pressure gradient. AB - The aim of this study was to evaluate the mechanical triggers that may cause plaque rupture. Wall shear stress (WSS) and pressure gradient are the direct mechanical forces acting on the plaque in a stenotic artery. Their influence on plaque stability is thought to be controversial. This study used a physiologically realistic, pulsatile flow, two-dimensional, cine phase-contrast MRI sequence in a patient with a 70% carotid stenosis. Instead of considering the full patient-specific carotid bifurcation derived from MRI, only the plaque region has been modelled by means of the idealised flow model. WSS reached a local maximum just distal to the stenosis followed by a negative local minimum. A pressure drop across the stenosis was found which varied significantly during systole and diastole. The ratio of the relative importance of WSS and pressure was assessed and was found to be less than 0.07% for all time phases, even at the throat of the stenosis. In conclusion, although the local high WSS at the stenosis may damage the endothelium and fissure plaque, the magnitude of WSS is small compared with the overall loading on plaque. Therefore, pressure may be the main mechanical trigger for plaque rupture and risk stratification using stress analysis of plaque stability may only need to consider the pressure effect. PMID- 20348536 TI - Stress analysis of carotid atheroma in a transient ischaemic attack patient using the MRI-based fluid-structure interaction method. AB - Rupture of atherosclerotic plaque is a major cause of mortality. Plaque stress analysis, based on patient-specific multisequence in vivo MRI, can provide critical information for the understanding of plaque rupture and could eventually lead to plaque rupture prediction. However, the direct link between stress and plaque rupture is not fully understood. In the present study, the plaque from a patient who recently experienced a transient ischaemic attack (TIA) was studied using a fluid-structure interaction method to quantify stress distribution in the plaque region based on in vivo MR images. The results showed that wall shear stress is generally low in the artery with a slight increase at the plaque throat owing to minor luminal narrowing. The oscillatory shear index is much higher in the proximal part of the plaque. Both local wall stress concentrations and the relative stress variation distribution during a cardiac cycle indicate that the actual plaque rupture site is collocated with the highest rupture risk region in the studied patient. PMID- 20348537 TI - An objective approach to digital removal of saccular aneurysms: technique and applications. AB - Human studies of haemodynamic factors in the pathogenesis of cerebral aneurysms require knowledge of the pre-aneurysmal vasculature. This paper presents an objective and automated technique to digitally remove an aneurysm and reconstruct the parent artery, based on lumen geometries segmented from angiographic images. Relying on robust computational geometry concepts, notably Voronoi diagrams of the digitised lumen surface, the aneurysm attachment region is first defined objectively using lumen centrelines. Centrelines within this region are replaced by smooth interpolations, which then guide the interpolation of Voronoi points within the attachment region. Combined with Voronoi points from outside the attachment region, the parent artery lumen, without the aneurysm, can be reconstructed. Plausible reconstructions were obtained, automatically, for a set of 10 side-wall or terminal aneurysms, of various sizes and shapes, from the ANEURISK project data set. Application of image-based computational fluid dynamics analysis to a five side-wall aneurysm cases data set revealed an association between the recently proposed gradient oscillatory number (GON) and the site of aneurysm formation in four of five cases; however, elevated GON was also evident at non-aneurysmal sites. A potential application to the automated delineation of aneurysms for morphological characterisations is also suggested. The proposed approach may serve as a broad platform for investigating haemodynamic and morphological factors in aneurysm initiation, rupture and therapy in a way amenable to large-scale clinical studies or routine clinical use. Nevertheless, while the parent artery reconstructions are plausible, it remains to be proven that they are faithful representations of the pre-aneurysmal artery. PMID- 20348538 TI - Computational modelling for cerebral aneurysms: risk evaluation and interventional planning. AB - Advanced computational techniques offer a new array of capabilities in the healthcare provision for cerebral aneurysms. In this paper information is provided on specific simulation methodologies that address some of the unanswered questions about intracranial aneurysm and their treatment. These include the evaluation of rupture risk, the thrombogenic characteristics of specific lesions and the efficacy assessment of particular interventional techniques and devices (e.g. endovascular coil embolisation and flow diversion using stents). The issues connected with ease-of-use and interactivity of computed simulations is discussed, and it is concluded, that the potential of these techniques to optimise planning of complex and multifaceted interventions is very significant, in spite of the fact that most of the methodologies described are still being developed and perfected. PMID- 20348539 TI - High-level antibiotic resistance in Pseudomonas aeruginosa biofilm: the ndvB gene is involved in the production of highly glycerol-phosphorylated beta-(1->3) glucans, which bind aminoglycosides. AB - Pseudomonas aeruginosa is an opportunistic pathogen that affects immunocompromised individuals and causes life-threatening infections in cystic fibrosis (CF) patients. Colonization of CF lung by P. aeruginosa involves a biofilm mode of growth, which is promoted by the production of exopolysaccharides. These polymers are essential components of the extracellular biofilm matrix. P. aeruginosa possesses several clusters contributing to the formation of the matrix, including the pel or psl genes. In the present study, we identified anionic cyclic glucans produced by P. aeruginosa, which are associated with the matrix of strains PAKDeltaretS and PA14. Their structure has been elucidated using chemical analysis, 1- and 2D nuclear magnetic resonance techniques and mass spectrometry. They belong to a family of cyclic beta-(1-->3) linked glucans of 12-16 glucose residues with 30-50% of glucose units substituted by 1-phosphoglycerol at O-6. These glucans were also recovered in pel mutant strains, which indicated that their biosynthesis was pel independent. In an effort to understand the biogenesis of these glucans, we analyzed the matrix components of a previously characterized P. aeruginosa PA14 mutant, the PA14::ndvB mutant strain. The ndvB gene was predicted to be involved in the synthesis of perisplasmic glucans, capable of physically interacting with aminoglycoside antibiotics. We revealed that the highly glycerol-phosphorylated beta-(1-->3)-glucans are lacking in the ndvB mutant, and we showed that these glucans are capable of direct binding with the aminoglycoside antibiotic kanamycin. This observation fills a gap in our understanding of the relationship between biofilm, cyclic glucans and high-level antibiotic resistance. PMID- 20348540 TI - Genomic SELEX for Hfq-binding RNAs identifies genomic aptamers predominantly in antisense transcripts. AB - An unexpectedly high number of regulatory RNAs have been recently discovered that fine-tune the function of genes at all levels of expression. We employed Genomic SELEX, a method to identify protein-binding RNAs encoded in the genome, to search for further regulatory RNAs in Escherichia coli. We used the global regulator protein Hfq as bait, because it can interact with a large number of RNAs, promoting their interaction. The enriched SELEX pool was subjected to deep sequencing, and 8865 sequences were mapped to the E. coli genome. These short sequences represent genomic Hfq-aptamers and are part of potential regulatory elements within RNA molecules. The motif 5'-AAYAAYAA-3' was enriched in the selected RNAs and confers low-nanomolar affinity to Hfq. The motif was confirmed to bind Hfq by DMS footprinting. The Hfq aptamers are 4-fold more frequent on the antisense strand of protein coding genes than on the sense strand. They were enriched opposite to translation start sites or opposite to intervening sequences between ORFs in operons. These results expand the repertoire of Hfq targets and also suggest that Hfq might regulate the expression of a large number of genes via interaction with cis-antisense RNAs. PMID- 20348541 TI - Proteomics analysis of the estrogen receptor alpha receptosome. AB - The estrogen receptors (ERs) are ligand-dependent transcription factors that activate transcription by binding to estrogen response elements. Estrogen mediated effects are tissue- and cell type-specific, determined by the cofactor recruitment to the ERs among other factors. To understand these differences in estrogen action, it is important to identify the various compositions of the ER complexes (ER receptosomes). In this report, we describe a fast and efficient method for the isolation of the ERalpha receptosome for proteomics analysis. Using immobilized estrogen response element on a Sepharose column in combination with two-dimensional electrophoresis and MALDI-TOF MS, significant amounts of proteins could be isolated and identified. Differences in ERalpha complex composition with the ER ligands 17beta-estradiol, 4-hydroxytamoxifen, and ICI 182,780 could also be observed. Thus, this approach provides an easy and relevant way of identifying ERalpha cofactor and transcription factor recruitment under different conditions. PMID- 20348542 TI - Proteomics and peritoneal dialysis: early days but clear potential. PMID- 20348543 TI - Standard Kt/V thresholds to accurately predict single-pool Kt/V targets for children receiving thrice-weekly maintenance haemodialysis. AB - BACKGROUND: Urea standard Kt/V (stdKt/V) provides a tool to normalize weekly small solute clearance for patients dialysed at various intervals, but it has not been studied in the paediatric haemodialysis (HD) population. METHODS: Using retrospective monthly adequacy data from children with end-stage renal disease receiving chronic thrice-weekly haemodialysis (n = 30), single-pool (spKt/V), equilibrated (eKt/V) and standard Kt/V (stdKt/V) were calculated for each individual HD session. eKt/V was estimated using Goldstein's logarithmic extrapolation method. Standard Kt/V was calculated using Leypoldt's formula based on eKt/V, duration and dialysis frequency. A spKt/V vs stdKt/V dose/frequency table was then derived from our thrice-weekly data. RESULTS: Using spKt/V of >or=1.2 as the minimal acceptable HD dose, receiver operating characteristic curve analysis was used to determine the corresponding target stdKt/V across a number of potential cutoff values. Single-pool Kt/V >or=1.2 was delivered with near certainty [sensitivity: 93.5%, specificity: 96.7%, area under the curve (AUC): 0.98] when a stdKt/V >or=2.0 was targeted. For a spKt/V >or=1.4, a target of stdKt/V >or=2.2 provided sensitivity and specificity of 73.4 and 96.1%, respectively, with an AUC of 0.94. CONCLUSIONS: Our data demonstrate that one should deliver a stdKt/V >or=2.0 for thrice-weekly paediatric HD in order to achieve a spKt/V >or=1.2; and if one wishes to ensure a spKt/V >or=1.4, then the stdKt/V must be >or=2.2. For children receiving a spKt/V >or=1.6 more than thrice weekly, the currently published adult dose/frequency table will overestimate the stdKt/V dose delivered and should be replaced by paediatric derived values. PMID- 20348544 TI - Transcriptional comparisons between equine articular repair tissue, neonatal cartilage, cultured chondrocytes and mesenchymal stromal cells. AB - Human and equine cell transplant strategies for cartilage lesions usually result in scar tissue that is similar to what is produced naturally during the repair process. In this study, culture-expanded de-differentiated chondrocytes and primary bone marrow stromal cells at a pre-transplantation time-point were compared along with neonatal cartilage to repair tissue. Transcriptional profiling using a 9413-probeset equine-specific cDNA microarray and targeted real time quantitative polymerase chain reaction validation were used to characterize relationships between these cell types and repair tissue both broadly and for individual cartilage biomarkers. The greatest divergence in expression was detected for transcripts encoding matrix proteins that typically define the differentiation status of normal articular cartilage and fibrocartilage repair tissue. Expression patterns and gene ontology analyses indicated that while the repair cells were more chondrogenic than bone marrow stromal cells and de differentiated cultured chondrocytes, steady-state levels of transcripts encoding cartilage biomarkers were substantially lower than the amounts found in neonatal articular cartilage. By characterizing gene expression differences amongst these tissues, we present important targets to monitor when developing improvements to cartilage engineering therapies. PMID- 20348545 TI - Multi-threaded vectorized distance matrix computation on the CELL/BE and x86/SSE2 architectures. AB - SUMMARY: Multiple sequence alignment is an important tool in bioinformatics. Although efficient heuristic algorithms exist for this problem, the exponential growth of biological data demands an even higher throughput. The recent emergence of multi-core technologies has made it possible to achieve a highly improved execution time for many bioinformatics applications. In this article, we introduce an implementation that accelerates the distance matrix computation on x86 and Cell Broadband Engine, a homogeneous and heterogeneous multi-core system, respectively. By taking advantage of multiple processors as well as Single Instruction Multiple Data vectorization, we were able to achieve speed-ups of two orders of magnitude compared to the publicly available implementation utilized in ClustalW. AVAILABILITY AND IMPLEMENTATION: Source codes in C are publicly available at https://sourceforge.net/projects/distmatcomp/ CONTACT: adri0004@ntu.edu.sg PMID- 20348546 TI - SICAGO: Semi-supervised cluster analysis using semantic distance between gene pairs in Gene Ontology. AB - SUMMARY: Despite the importance of using the semantic distance to improve the performance of conventional expression-based clustering, there are few freely available software that provides a clustering algorithm using the ontology-based semantic distances as prior knowledge. Here, we present the SICAGO (SemI supervised Cluster Analysis using semantic distance between gene pairs in Gene Ontology) system that helps to discover the groups of genes more effectively using prior knowledge extracted from Gene Ontology. AVAILABILITY: http://ai.cau.ac.kr/sicago.html CONTACT: dwkim@cau.ac.kr PMID- 20348547 TI - Clinical and therapeutic aspects of Klinefelter's syndrome: sexual function. AB - Klinefelter's syndrome (KS) is the most common sex chromosomal aberration among men, with estimated prevalence of about 1 in 500 newborn males. The classical phenotype of KS is widely recognized, but many affected subjects present only very mild signs. While the association between KS and infertility has been well documented, few studies have investigated sexual function in the KS patients. In the present paper we reviewed studies addressed to emotional processing and sexual function in KS. We searched the following databases Medline, Pubmed, Embase, for Klinefelter's syndrome, sexuality. We focus on the peculiar contribution of genetic and hormonal background, which characterizes sexual dysfunction in KS. Abnormal structure and function of the emotional brain circuits have been described in KS. These alterations were less pronounced when the patients underwent to testosterone replacement therapy suggesting that they were mediated by testosterone deficiency. Accordingly, clinical studies indicate that sexual dysfunctions, eventually present in KS, are not specifically associated with the syndrome but are related to the underlying hypogonadism. In conclusion, androgen deficiency more than chromosomal abnormality is the major pathogenic factor of sexual dysfunction in KS. PMID- 20348548 TI - Osteoporosis in Klinefelter's syndrome. AB - Hypogonadism represents one of the most important causes of male osteoporosis. Testosterone regulates male bone metabolism both indirectly by aromatization to estrogens and directly through the androgen receptor (AR) on osteoblasts, promoting periosteal bone formation during puberty and reducing bone resorption during adult life. Early onset of testosterone deficiency, as observed in Klinefelter's syndrome (KS), is an important risk factor for precocious osteoporosis. Osteoporosis is present in up to 40% of subjects with KS and has usually been attributed to low testosterone levels. However, reduced bone mass might be present also in KS men with normal testosterone levels and testosterone replacement therapy does not always restore bone density in KS patients. Possible new determinants for osteoporosis in KS might be related to the AR function and insulin-like factor 3 (INSL3) levels. The CAG length and inactivation pattern of the AR in KS have been related to osteoporosis, but definitive proof is lacking. INSL3 has an anabolic role on bone metabolism by acting on osteoblasts and INSL3 levels are low in KS. Therefore, low INSL3 concentrations might represent a possible new pathogenic mechanism for reduced bone mass in KS. PMID- 20348549 TI - Myostatin: an overlooked player in heart failure? PMID- 20348550 TI - Myostatin activation in patients with advanced heart failure and after mechanical unloading. AB - AIMS: Myostatin inhibits myoblast differentiation/proliferation and may play a role in heart failure (HF) and reverse remodelling after left ventricular assist device (LVAD) support. This study sought to characterize myostatin expression and activation in advanced HF before and after LVAD support. METHODS AND RESULTS: Left ventricular tissue pairs were collected at LVAD implantation (core) and at cardiac transplantation/LVAD explantation in patients with advanced ischaemic (ICM-ischaemic cardiomyopathy) and non-ischaemic (DCM-dilated cardiomyopathy) HF. Normal cardiac tissue (control) was obtained from hearts not placed for transplantation. Serum was collected independently from patients with stable DCM HF and from healthy controls. Full-length and cleaved propeptide myostatin levels were quantified by western blot analysis. Dilated cardiomyopathy propeptide levels at core were significantly higher than control and significantly increased after LVAD support. Ischaemic cardiomyopathy propeptide levels were higher than control, but did not change after LVAD support. No changes in full-length levels were seen. Serum myostatin levels were significantly higher in DCM HF patients than in healthy controls. CONCLUSION: This is the first clinical evidence that myostatin activation is increased in HF. Myostatin may affect cardiac hypertrophy and may mediate regression of cellular hypertrophy after mechanical unloading. PMID- 20348551 TI - Impaired myocardial perfusion in atrial fibrillation cause or effect? PMID- 20348552 TI - Cryoablation of superoparaseptal and septal accessory pathways: a single centre experience. AB - AIMS: Radiofrequency (RF) catheter ablation in the septum close to the atrioventricular (AV) node or His bundle has an increased risk of irreversible complications. Cryothermal energy has the advantages of reversible cryomapping and increased catheter stability. This study evaluates the usefulness of cryoablation in superoparaseptal and septal accessory pathways (APs). METHODS AND RESULTS: Twenty-seven consecutive patients (16 men, 11 women, median age 29 years, range 15-65) underwent cryoablation for APs either located in the superoparaseptal (n=18) or septal (n=9) area. Cryomapping, using exclusively a 6 mm tip catheter, at -30 degrees C was performed before ablation with a goal temperature of -80 degrees C for 240 s. Acute success was achieved in 26 out of 27 patients (96%). Total procedure and fluoroscopy time was 163+/-61 and 30+/-22 min, respectively. During a follow-up for a mean of 996+/-511 days, seven patients (27%) had recurrences of arrhythmia. Five out of these seven underwent a second cryoablation with successful results, giving a total success rate of 89%. Two patients developed transient second degree AV block during cryoablation; however, no permanent AV block was observed. The recurrence rate was significantly higher in patients with procedure-related transient mechanical AP block (6/7; 86%) due to catheter trauma compared with those without mechanical block (5/20; 25%; P=0.006). CONCLUSION: Cryoablation of the superoparaseptal and septal APs is a safe and effective alternative to RF therapy. Procedure-related transient mechanical AP block predicts worse late outcome. PMID- 20348553 TI - New diagnosis of arrhythmogenic right ventricular cardiomyopathy in an octogenarian with the help of Fontaine electrocardiographic leads. AB - We report an 85-year-old man with arrhythmogenic right ventricular cardiomyopathy who presented with monomorphic ventricular tachycardia. This is the oldest patient recorded with this disease. The presence of epsilon waves by the Fontaine lead system provided a high degree of suspicion for the disease. PMID- 20348554 TI - Left ventricular sensing and pacing for sensing difficulties in internal cardioverter defibrillator therapy for arrhythmogenic right ventricular cardiomyopathy. AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease where therapy with an internal cardioverter defibrillator (ICD) is frequently indicated, but the use of these devices is often challenged because of sensing dysfunction with low right ventricular sensing amplitude. We present the case of an ARVC patient in whom ICD sensing difficulties were overcome by the implantation of a coronary sinus lead for pacing and sensing. PMID- 20348555 TI - Late failure of a single-coil transvenous implantable cardioverter-defibrillator lead associated with conductor separation. AB - Two patients with the same model of single-coil active fix implantable defibrillator lead presented with evidence of lead malfunction, in one case with an abrupt rise in pacing impedance and threshold and in the other with evidence of over-sensing. In both cases, the chest radiograph showed separation of conductors in the defibrillation lead from the main body of the lead. PMID- 20348556 TI - Comparison of ovarian function markers in users of hormonal contraceptives during the hormone-free interval and subsequent natural early follicular phases. AB - OBJECTIVE: The aim of this study was to evaluate whether values of FSH, LH, estradiol, anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume (OV) determined on day 7 of the hormone-free interval are similar to values measured on days 2-5 of two subsequent natural menstrual cycles. In addition, values measured on day 7 of the hormone-free interval were examined for the purpose of predicting values measured on days 2-5 during the second natural cycle. METHODS: In this study, 25 women using hormonal contraception provided a blood sample and underwent transvaginal ultrasound measurements on day 7 of the hormone-free interval and on cycle days 2-5 of two subsequent natural cycles. Changes were compared by repeated measures ANOVA and multivariate linear regression was used for prediction purposes. RESULTS: Mean (SD) age of the participants was 26.3 (6.2) years. Overall significant decreases in FSH and inhibin B and significant increases in AMH, AFC and ovarian volume values were measured after discontinuation of hormonal contraception (P < 0.001, P = 0.04, P = 0.01, P < 0.001 and P = 0.004, respectively). Significant changes occurred both from day 7 of the hormone-free interval to natural cycle 1 as well as from natural cycle 1 to natural cycle 2. FSH, AMH and AFC values measured during days 2-5 of natural cycle 2 could be predicted by the corresponding values measured on day 7 of the hormone-free interval. CONCLUSION: Hormonal and ultrasound markers of ovarian function in hormonal contraception users measured at the end of the hormone-free interval do not seem to represent subsequent natural early follicular phase values. However, these values can, in some cases (FSH, AMH and AFC), be used to predict early follicular phase values using calculated prediction equations, which need to be validated in future research. PMID- 20348557 TI - Automated detection of follow-up appointments using text mining of discharge records. AB - OBJECTIVE: To determine whether text mining can accurately detect specific follow up appointment criteria in free-text hospital discharge records. DESIGN: Cross sectional study. SETTING: Mayo Clinic Rochester hospitals. PARTICIPANTS: Inpatients discharged from general medicine services in 2006 (n = 6481). INTERVENTIONS: Textual hospital dismissal summaries were manually reviewed to determine whether the records contained specific follow-up appointment arrangement elements: date, time and either physician or location for an appointment. The data set was evaluated for the same criteria using SAS Text Miner software. The two assessments were compared to determine the accuracy of text mining for detecting records containing follow-up appointment arrangements. MAIN OUTCOME MEASURES: Agreement of text-mined appointment findings with gold standard (manual abstraction) including sensitivity, specificity, positive predictive and negative predictive values (PPV and NPV). RESULTS: About 55.2% (3576) of discharge records contained all criteria for follow-up appointment arrangements according to the manual review, 3.2% (113) of which were missed through text mining. Text mining incorrectly identified 3.7% (107) follow-up appointments that were not considered valid through manual review. Therefore, the text mining analysis concurred with the manual review in 96.6% of the appointment findings. Overall sensitivity and specificity were 96.8 and 96.3%, respectively; and PPV and NPV were 97.0 and 96.1%, respectively. ANALYSIS: of individual appointment criteria resulted in accuracy rates of 93.5% for date, 97.4% for time, 97.5% for physician and 82.9% for location. CONCLUSION: Text mining of unstructured hospital dismissal summaries can accurately detect documentation of follow-up appointment arrangement elements, thus saving considerable resources for performance assessment and quality-related research. PMID- 20348558 TI - A model for medication safety event detection. AB - BACKGROUND: Hospital medication safety event detection predominantly emphasizes the identification of preventable adverse drug events (ADEs) through self reports. These relatively rare events only provide insight into patient harm and self-reports identify only a small portion of ADEs. A broader system-focused approach to medication safety event detection that uses an array of event detection methods is recommended. This approach illuminates medication system deficits and supports improvement strategies that can prevent future patient risk. OBJECTIVE: To: (i) describe a system-focused approach to hospital medication safety event detection, and (ii) present a case illustration of approach application. SYSTEM-FOCUSED MODEL AND METHODOLOGY: A three-level medication safety event detection model that ranges from a narrow harm-focused to broader system-focused approach is described. A standardized cross-level methodology to detect medication safety events is presented. CASE ILLUSTRATION: A Level 3 system-focused methodology that incorporated both voluntary and non voluntary event detection strategies was used in 17 critical care (n = 4), intermediate care (n = 7) and medical-surgical units (n = 6) across two hospitals. A total of 431 events were detected: 78 (18.1%) ADEs and 353 (81.9%) potential ADEs. Of the 353 PADEs, 302 (70.0%) were non-intercepted events. Non voluntary detection methods yielded the majority of events (367, 85.1%). CONCLUSIONS: The incidence of ADEs was low when compared with non-intercepted PADEs. This was indicative of medication safety system failures that placed patients at risk for potential harm. Non-voluntary detection methods were much more effective at detecting events than traditional self-report methods. PMID- 20348559 TI - Fruit and seed heteromorphism in the cold desert annual ephemeral Diptychocarpus strictus (Brassicaceae) and possible adaptive significance. AB - BACKGROUND AND AIMS: Diptychocarpus strictus is an annual ephemeral in the cold desert of northwest China that produces heteromorphic fruits and seeds. The primary aims of this study were to characterize the morphology and anatomy of fruits and seeds of this species and compare the role of fruit and seed heteromorphism in dispersal and germination. METHODS: Shape, size, mass and dispersal of siliques and seeds and the thickness of the mucilage layer on seeds were measured, and the anatomy of siliques and seeds, the role of seed mucilage in water absorption/dehydration, germination and adherence of seeds to soil particles, the role of pericarp of lower siliques in seed dormancy and seed after ripening and germination phenology were studied using standard procedures. KEY RESULTS: Plants produce dehiscent upper siliques with a thin pericarp containing seeds with large wings and a thick mucilage layer and indehiscent lower siliques with a thick pericarp containing nearly wingless seeds with a thin mucilage layer. The dispersal ability of seeds from the upper siliques was much greater than that of intact lower siliques. Mucilage increased the amount of water absorbed by seeds and decreased the rate of dehydration. Seeds with a thick mucilage layer adhered to soil particles much better than those with a thin mucilage layer or those from which mucilage had been removed. Fresh seeds were physiologically dormant and after-ripened during summer. Non-dormant seeds germinated to high percentages in light and in darkness. Germination of seeds from upper siliques is delayed until spring primarily by drought in summer and autumn, whereas the thick, indehiscent pericarp prevents germination for >1 year of seeds retained in lower siliques. CONCLUSIONS: The life cycle of D. strictus is morphologically and physiologically adapted to the cold desert environment in time and space via a combination of characters associated with fruit and seed heteromorphism. PMID- 20348560 TI - Comment and response in Attention, Perception, & Psychophysics. PMID- 20348562 TI - Timing and time perception: a review of recent behavioral and neuroscience findings and theoretical directions. AB - The aim of the present review article is to guide the reader through portions of the human time perception, or temporal processing, literature. After distinguishing the main contemporary issues related to time perception, the article focuses on the main findings and explanations that are available in the literature on explicit judgments about temporal intervals. The review emphasizes studies that are concerned with the processing of intervals lasting a few milliseconds to several seconds and covers studies issuing from either a behavioral or a neuroscience approach. It also discusses the question of whether there is an internal clock (pacemaker counter or oscillator device) that is dedicated to temporal processing and reports the main hypotheses regarding the involvement of biological structures in time perception. PMID- 20348563 TI - The unilateral field advantage in repetition detection: effects of perceptual grouping and task demands. AB - This study examines interhemispheric interactions in detecting objects that are simultaneously repeated in an array of objects. Previous studies have shown that presenting two identical objects to a single hemifield speeds up repetition detection. This unilateral field advantage (UFA) is often attributed to the relatively low-level processing demands for detecting a perceptual repetition, and more specifically, to more efficient perceptual grouping processes within a hemisphere than between hemispheres. To directly examine the impact of perceptual grouping and task demands on interhemispheric interactions, we asked participants to judge whether four items, one presented in each visual quadrant, were all different, or whether any two were the same, along an instructed dimension. We found that in comparison with the UFA for identical objects, the UFA for repetition detection in accuracy was similar or greater when the matching objects were not perceptually identical and differed in color, size, or viewpoint. Thus, decreasing grouping strength and increasing computational complexity did not reduce the UFA. Results are interpreted in terms of the callosal degradation account of the UFA. PMID- 20348564 TI - Holistic processing underlies gender judgments of faces. AB - In three experiments, we investigated whether holistic processing underlies gender judgments about faces. Chinese participants were asked to make gender judgments for inverted, scrambled, or composite faces. Results showed that judgments were dramatically impaired by these manipulations (as compared with performance for normal upright faces), demonstrating three hallmark effects of holistic face processing that have been observed in perception of face identity. Whether the test faces were Chinese or Caucasian showed no effect on holistic processing of gender perception, in contrast to studies of identity analysis. These results suggest that holistic processing is a general mechanism for different aspects of face perception and are consistent with the idea that physiognomic properties that determine the gender of a face are universal, rather than race specific. PMID- 20348565 TI - Object-based eye movements: the eyes prefer to stay within the same object. AB - The present study addressed the question of whether we prefer to make eye movements within or between objects. More specifically, when fixating one end of an object, are we more likely to make the next saccade within that same object or to another object? Observers had to discriminate small letters placed on rectangles similar to those used by Egly, Driver, and Rafal (1994). Following an exogenous cue, observers made a saccade to one end of one of the rectangles. The small target letter, which could be discriminated only after it had been fixated, could appear either within the same or at a different object. Consistent with object-based attention, we show that observers prefer to make an eye movement to the other end of the fixated same object, rather than to the equidistant end of a different object. It is concluded that there is a preference to make eye shifts within the same object, rather than between objects. PMID- 20348566 TI - Individual differences in dispositional focus of attention predict attentional blink magnitude. AB - When identifying two targets presented in a rapid serial visual presentation stream, one's accuracy on the second target is reduced if it is presented shortly (within 500 msec) after the first target-an attentional blink (AB). Individuals differ greatly in the size of their AB. One way to learn about the AB is to understand what underlies these individual differences. Recent studies have suggested that when a broadened or diffused attentional state is induced, the AB deficit can be attenuated. The present study examined whether natural (dispositional) individual differences in focus and diffusion of attention as assessed by the global/local task could predict performance on the AB task. Performance that was consistent with diffusion correlated negatively with AB size, and performance that was consistent with focusing correlated positively with AB size, showing that dispositional focus and diffusion of attention can predict individual differences in the AB. These findings are consistent with the Olivers and Nieuwenhuis (2006) overinvestment hypothesis. PMID- 20348567 TI - Perceptual grouping operates independently of attentional selection: evidence from hemispatial neglect. AB - To what extent can human observers process visual information that is not currently the focus of attention? We evaluated the extent to which unattended visual information (i.e., that which appears on the neglected side of space in individuals with hemispatial neglect) is perceptually organized and influences the perceptual processing of information on the attended side. To examine this, patients (and matched controls) judged whether successive, complex checkerboard stimuli (targets), presented entirely to their intact side of space, were the same or different. Concurrent with this demanding task, irrelevant distractor elements appeared on the unattended side and either changed or retained their perceptual grouping on successive displays, independently of changes in the ipsilesional task-relevant target. Changes in the grouping of the unattended task irrelevant distractor elements produced congruency effects on the attended target change judgment to the same extent in the neglect patients as in the control participants, and this was true even in those patients with severe attentional deficits. These results suggest that some perceptual processes, such as grouping, can operate in the absence of attention. PMID- 20348568 TI - Comment on Shomstein, Kimchi, Hammer, and Behrmann (2010): a case study in methodological anosagnosia? AB - Shomstein, Kimchi, Hammer, and Behrmann (2010) try to capitalize on the apparent dissociation between vision and the processes that seem to mediate neglect patients' attentional selection and awareness to investigate the processing of perceptual grouping in the absence of visual attention. We argue that to assess this type of dissociation requires specific methodological adaptations to determine whether visual attention is in operation. We caution that Shomstein et al.'s article does not present convincing evidence of grouping without attentional selection because they do not directly assess attentional selection in their experimental task. PMID- 20348569 TI - Spatial updating of dynamic scenes: tracking multiple invisible objects across viewpoint changes. AB - Research on dynamic attention has shown that visual tracking is possible even if the observer's viewpoint on the scene holding the moving objects changes. In contrast to smooth viewpoint changes, abrupt changes typically impair tracking performance. The lack of continuous information about scene motion, resulting from abrupt changes, seems to be the critical variable. However, hard onsets of objects after abrupt scene motion could explain the impairment as well. We report three experiments employing object invisibility during smooth and abrupt viewpoint changes to examine the influence of scene information on visual tracking, while equalizing hard onsets of moving objects after the viewpoint change. Smooth viewpoint changes provided continuous information about scene motion, which supported the tracking of temporarily invisible objects. However, abrupt and, therefore, discontinuous viewpoint changes strongly impaired tracking performance. Object locations retained with respect to a reference frame can account for the attentional tracking that follows invisible objects through continuous scene motion. PMID- 20348570 TI - Are the effects of attention on speed judgments genuinely perceptual? AB - A number of studies in recent years have suggested that exogenous and endogenous attention might enhance the perceived magnitude of various perceptual attributes, such as contrast and motion speed. Those studies have generally used comparative judgments as a measure to assess the point of subjective equality; however, similarity judgments have been proposed as possibly less prone to decision biases (Schneider & Komlos, 2008). In three experiments, using a similarity judgment task, we did not find any evidence of motion speed enhancement by exogenous attention. We suggest that the effect revealed by comparative judgments arises at the decisional, rather than the perceptual, stage. PMID- 20348571 TI - From reorienting of attention to biased competition: evidence from hemifield effects. AB - When a distractor was presented simultaneously with or directly following a target, it produced more interference when it was presented in the same visual hemifield as the target than when it was presented in the opposite visual field. This result is interpreted in terms of biased competition; there is more competition between stimuli when they are presented in the same visual field, rather than in opposite visual fields. However, when the distractor was presented 125 msec or more prior to the target, this pattern was reversed. In those cases, there was more distractor interference when target and distractor were presented in opposite visual fields. This can be explained by assuming that attention was captured by the distractor, and that there was an additional cost of reorienting to a location in the opposite visual field. PMID- 20348572 TI - Nonspatial interdimensional attentional capture. AB - Accuracy in identifying a target is impaired by a task-irrelevant singleton distractor even when the target and distractor appear in the same location. However, whether this impairment, known as a nonspatial interdimensional attentional capture, is contingent on a top-down attentional set or determined by stimulus-driven signals from distractors is unclear. To examine whether interdimensional attentional capture is affected by a top-down attentional set, the present study explicitly manipulated observers' search strategies (the singleton detection or feature search modes) and the number of objects consisting of the search items. The results indicated that interdimensional attentional capture occurred even under the feature search mode but that the capture effect decreased under this search mode irrespective of the number of distractors, suggesting that top-down knowledge was effective in modulating nonspatial interdimensional capture. PMID- 20348573 TI - Reduced attentional capture in action video game players. AB - Recent studies indicate that playing action video games improves performance on a number of attention-based tasks. However, it remains unclear whether action video game experience primarily affects endogenous or exogenous forms of spatial orienting. To examine this issue, action video game players and non-action video game players performed an attentional capture task. The results show that action video game players responded quicker than non-action video game players, both when a target appeared in isolation and when a salient, task-irrelevant distractor was present in the display. Action video game players additionally showed a smaller capture effect than did non-action video game players. When coupled with the findings of previous studies, the collective evidence indicates that extensive experience with action video games may enhance players' top-down attentional control, which, in turn, can modulate the negative effects of bottom up attentional capture. PMID- 20348574 TI - Abrupt onsets capture attention independent of top-down control settings II: additivity is no evidence for filtering. AB - Is attentional capture contingent on top-down control settings or involuntarily driven by salient stimuli? Supporting the stimulus-driven attentional capture view, Schreij, Owens, and Theeuwes (2008) found that an onset distractor caused a response delay, in spite of participants' having adopted an attentional set for a color feature. However, Folk, Remington, and Wu (2009) claimed that this delay reflects separate, nonspatial filtering costs instead, because the onset effects were additive with color-based capture effects, and capture should have caused underadditivity. The present Experiment 1 shows that contingent capture caused by additional color cues is also additive, just like the onset effect. This makes additivity a dubious diagnostic with regard to spatial capture. Experiment 2 demonstrates that it is possible to obtain underadditivity when attention demanding distractors have sufficient capturing power. Experiment 3 shows that the abrupt onset interference turns into a benefit when the locations of the onset and the target coincide. Together, these results argue in favor of stimulus driven attentional capture by abrupt onsets. PMID- 20348575 TI - When do microsaccades follow spatial attention? AB - Following up on an exchange about the relation between microsaccades and spatial attention (Horowitz, Fencsik, Fine, Yurgenson, & Wolfe, 2007; Horowitz, Fine, Fencsik, Yurgenson, & Wolfe, 2007; Laubrock, Engbert, Rolfs, & Kliegl, 2007), we examine the effects of selection criteria and response modality. We show that for Posner cuing with saccadic responses, microsaccades go with attention in at least 75% of cases (almost 90% if probability matching is assumed) when they are first (or only) microsaccades in the cue-target interval and when they occur between 200 and 400 msec after the cue. The relation between spatial attention and the direction of microsaccades drops to chance level for unselected microsaccades collected during manual-response conditions. Analyses of data from four cross modal cuing experiments demonstrate an above-chance, intermediate link for visual cues, but no systematic relation for auditory cues. Thus, the link between spatial attention and direction of microsaccades depends on the experimental condition and time of occurrence, but it can be very strong. PMID- 20348576 TI - Mental-state attribution drives rapid, reflexive gaze following. AB - When presented with a face stimulus whose gaze is diverted, observers' attention shifts to locations fixated by the face. Such "gaze following" has been characterized by some previous studies as a consequence of sophisticated theory of mind processes, but by others (particularly those employing the "gaze-cuing" paradigm) as an involuntary response that is triggered directly and reflexively by the physical features of a face. To address this apparent contradiction, we modified the gaze-cuing paradigm using a deception procedure to convince observers that prerecorded videos of an experimenter making head turns and wearing mirrored goggles were a "live" video link to an adjacent room. In two experiments, reflexive gaze following was found when observers believed that the model was wearing transparent goggles and could see, but it was significantly reduced when they believed that the experimenter wore opaque goggles and could not see. These results indicate that the attribution of the mental state "seeing" to a face plays a role in controlling even reflexive gaze following. PMID- 20348577 TI - Examination of gaze behaviors under in situ and video simulation task constraints reveals differences in information pickup for perception and action. AB - Gaze and movement behaviors of association football goalkeepers were compared under two video simulation conditions (i.e., verbal and joystick movement responses) and three in situ conditions (i.e., verbal, simplified body movement, and interceptive response). The results showed that the goalkeepers spent more time fixating on information from the penalty kick taker's movements than ball location for all perceptual judgment conditions involving limited movement (i.e., verbal responses, joystick movement, and simplified body movement). In contrast, an equivalent amount of time was spent fixating on the penalty taker's relative motions and the ball location for the in situ interception condition, which required the goalkeepers to attempt to make penalty saves. The data suggest that gaze and movement behaviors function differently, depending on the experimental task constraints selected for empirical investigations. These findings highlight the need for research on perceptual-motor behaviors to be conducted in representative experimental conditions to allow appropriate generalization of conclusions to performance environments. PMID- 20348578 TI - Effects of intention and learning on attention to information in dynamic touch. AB - The current research distinguishes two types of attention shifts: those entailed by perceptual learning and those entailed by changing intention. In perceptual learning, participants given feedback have been shown to gradually shift attention toward the optimal (i.e., specifying) information variable for the task. A shift in variable use is also expected when intention changes, because an intention to perceive some property entails attunement to information about that property. We compared the effects of feedback and intention in a dynamic (kinesthetic) touch task by representing both as changes of locus in an information space of inertial variables. Participants wielded variously sized, unseen, rectangular parallelepipeds and made length or width judgments about them. When given feedback, participants made gradual attentional shifts toward the optimal variable, which demonstrates the education of attention. When asked to report a new property, participants made large attentional jumps to the ballpark of the optimal variable for the new property. Exploratory movements were measured on 6 participants and were found to differ as a function of intention and to change with learning. PMID- 20348579 TI - Eye-movement-driven changes in the perception of auditory space. AB - The perceptual localization of sensory stimuli often depends on body position, and, when action is required, sensory coordinates must be transformed into a motor reference frame. We investigated the role of such a reference frame change on visual and auditory spatial cognition. Participants had to make a saccade to a visual or auditory target and subsequently compare the location of a visual or auditory probe to the remembered location of the target. Neither visual nor auditory localization depended on trial-by-trial variability in saccade endpoint, suggesting that target locations are remapped across saccades in a manner allowing for oculomotor noise. We also compared visual and auditory localization performance before and after the systematic modification of saccade metrics by saccadic adaptation. Adaptation introduced systematic biases into transsaccadic visual and auditory localization behavior. These results show that information about eye movements is taken into account in both visual and auditory spatial cognition. We propose that auditory stimuli are remapped across saccades and that this eye-centered representation contributes to normal auditory localization. PMID- 20348580 TI - Effects of sign language experience on categorical perception of dynamic ASL pseudosigns. AB - We investigated effects of sign language experience on deaf and hearing participants' categorical perception of minimal manual contrast stimuli that met key criteria of speech perception research. A continuum of meaningless dynamic stimuli was created with a morphing approach, which manipulated videorecorded productions of phonotactically permissible pseudosigns differing between American Sign Language (ASL) handshapes that contrast on a single articulatory dimension (U-V: finger-spreading). AXB discrimination and AXB categorization and goodness ratings on the target items were completed by deaf early (native) signers (DE), deaf late (nonnative) signers (DL), hearing late (L2) signers (HL), and hearing nonsigners (HN). Categorization and goodness functions were less categorical and had different boundaries for DL participants than for DE and HL participants. Shape and level of discrimination functions also differed by ASL experience and hearing status, with DL signers showing better performance than DE, HL, and especially HN participants, particularly at the U end of the continuum. Although no group displayed a peak in discrimination at the category boundary, thus failing to support classic categorical perception, discrimination was consistent with categorization in other ways that differed among the groups. Thus, perception of phonetic variations underlying this minimal sign contrast is systematically affected by language experience. PMID- 20348581 TI - Abnormal pitch--time interference in congenital amusia: evidence from an implicit test. AB - Congenital amusia, characterized by a severe problem in detecting anomalies in melodies, is a lifelong disorder that has been ascribed to an acoustical pitch deficit. In the present study, we investigated how the perception of a duration is altered when it is bounded by tones varying in pitch. The results show that temporal accuracy is impaired by pitch variations as small as a quarter of a semitone in control participants, whereas it is impaired only when pitch variations are increased to 4 semitones in congenital amusics. Furthermore, control participants associate intervals bounded by low- and high-pitched tones with long and short durations, respectively. Amusic participants do not make this connection, even with large pitch differences, pointing to a deficit in pitch time integration. Thus, our results are consistent with the notion that congenital amusia is linked to a neurogenetic anomaly that impairs pitch processing, independently of task factors. PMID- 20348582 TI - An intonational cue to word segmentation in phonemically identical sequences. AB - We investigated the use of language-specific intonational cues to word segmentation in French. Participants listened to phonemically identical sequences such as /selafi/, C'est la fiche/l'affiche "It's the sheet/poster." We modified the f0 of the first vowel /a/ of the natural consonant-initial production la fiche, so that it was equal to that of the natural vowel-initial production l'affiche (resynth-consonant-equal condition), higher (resynth-consonant-higher condition), or lower (resynth-consonant-lower condition). In a two-alternative forced choice task (Experiment 1), increasing the f0 in the /a/ of la fiche increased the percentage of vowel-initial (affiche) responses. In Experiment 2, participants made visual lexical decisions to vowel-initial targets (affiche) following both the natural consonant-initial production (la fiche) and the resynth-consonant-equal version. Facilitation was found only for the resynth consonant-equal condition, suggesting that raising the f0 allowed online activation of vowel-initial targets. The recognition system seems to exploit intonational information to guide segmentation toward the beginning of content words. PMID- 20348583 TI - The effects of age on channel capacity for absolute identification of tonal duration. AB - We compared the ability of younger and older adults to identify which 2-kHz tones of eight varying durations was presented on a trial with their ability to discriminate between adjacent pairs of duration-varying tones drawn from the same set. We used signal detection analyses to construct scales of perceived duration for both tasks. Scales derived from pairwise comparisons of adjacent durations were related linearly to the logarithm of stimulus duration; these were essentially identical in younger and older adults. However, scales derived from the eight-alternative absolute identification experiments, which were also linearly related to the logarithm of duration, indicated that older adults outperformed younger adults on this task. These results suggest that the ability to process large numbers of stimuli that differ only in duration is at least as good, if not better, in older than in younger adults, relative to the ability of each group to discriminate between two stimuli differing only in duration. PMID- 20348584 TI - How big is the gap between olfactory detection and recognition of aliphatic aldehydes? AB - The aim of the present study was to determine the magnitude of the difference in concentration between olfactory detection and recognition thresholds of aliphatic aldehydes. To this end, we first determined olfactory detection thresholds for n butanal, n-pentanal, n-hexanal, n-heptanal, and n-octanal in a group of 16 subjects and then assessed their ability to discriminate between all possible binary pairs of the same odorants presented at different concentrations above their individual detection thresholds. We found that the gap between detection and recognition of aliphatic aldehydes is odorant pair dependent and, at the group level, spans at least a factor of 100. However, single subjects successfully discriminated between certain aldehyde pairs presented at a factor as low as 3 above detection threshold. Our approach to determining olfactory recognition thresholds, using a performance-based measure rather than verbal labeling, not only avoids the problem of semantic ambiguity and arguable criteria, but also is applicable to nonhuman species, allowing for interspecific comparisons of recognition thresholds and of the gap between detection and recognition of odorants. The raw discrimination data from this study are available as a supplement from http://app.psychonomic journals.org/content/supplemental. PMID- 20348585 TI - Visual and haptic influence on perception of stimulus size. AB - In six experiments, subjects judged the sizes of squares that were presented visually and/or haptically, in unimodal or bimodal conditions. We were interested in which mode most affected size judgments in the bimodal condition when the squares presented to each mode actually differed in size. Three factors varied: whether haptic exploration was passive or active, whether the choice set from which the subjects selected their responses was visual or haptic, and whether cutaneous information was provided in addition to kinesthetic information. To match the task for each mode, visual presentations consisted of a cursor that moved along a square pathway to correspond to the haptic experience of successive segments revealed during exploration. We found that the visual influence on size judgments was greater than the influence of haptics when the haptic experience involved only kinesthesis, passive movement, and a visual choice set. However, when cutaneous input was added to kinesthetic information, size judgments were most influenced by the haptic mode. The results support hypotheses of sensory integration, rather than capture of one sense by the other. PMID- 20348586 TI - Exploratory pressure influences haptic shape perception via force signals. AB - In this study of the haptic perception of small bumps, we investigated the influence of exploratory movement variation on signal integration and the percept's reliability. When sliding across a bump on a surface, the finger follows the geometry of the bump (i.e., the position signal). At the same time, patterns of forces depending on the gradient of the bump act on the finger (i.e., the force signal; Robles-de-la-Torre & Hayward, 2001). Consistent with the maximum likelihood estimation (MLE) model, haptically perceived shape can be described by a weighted average of the shapes signaled by the position and force signals (Drewing & Ernst, 2006; Ernst & Banks, 2002). Here, we found that the weights of the position and force signals and the reliability of the shape percept depend on the pressure (and velocity) of the exploratory movement (Experiment 1). These effects could not be traced back to pressure effects on the reliability of the single signals, as would be predicted from the MLE model (Experiment 2). However, we found that the signal-specific shape estimate derived from the force signal increases with increasing pressure (Experiment 3), and this bias can explain the perceptual effects of exploratory pressure. PMID- 20348587 TI - The race model inequality for censored reaction time distributions. AB - The race model inequality (RMI) introduced in Miller (1982) puts an upper limit on the amount of reaction time facilitation within the redundant-signals paradigm that is consistent with a race model. Here, it is shown through theoretical analysis and numerical simulation that inferences from the RMI test may become invalid when the experimenter misses a proportion of the responses by limiting the recording interval (right censoring) or excluding outliers from analysis (left and/or right censoring). Moreover, a correction of the inequality test for right-censored reaction time distributions is proposed. PMID- 20348588 TI - Peptide identification from mixture tandem mass spectra. AB - The success of high-throughput proteomics hinges on the ability of computational methods to identify peptides from tandem mass spectra (MS/MS). However, a common limitation of most peptide identification approaches is the nearly ubiquitous assumption that each MS/MS spectrum is generated from a single peptide. We propose a new computational approach for the identification of mixture spectra generated from more than one peptide. Capitalizing on the growing availability of large libraries of single-peptide spectra (spectral libraries), our quantitative approach is able to identify up to 98% of all mixture spectra from equally abundant peptides and automatically adjust to varying abundance ratios of up to 10:1. Furthermore, we show how theoretical bounds on spectral similarity avoid the need to compare each experimental spectrum against all possible combinations of candidate peptides (achieving speedups of over five orders of magnitude) and demonstrate that mixture-spectra can be identified in a matter of seconds against proteome-scale spectral libraries. Although our approach was developed for and is demonstrated on peptide spectra, we argue that the generality of the methods allows for their direct application to other types of spectral libraries and mixture spectra. PMID- 20348589 TI - Purification of the CaaX-modified, dynamin-related large GTPase hGBP1 by coexpression with farnesyltransferase. AB - Over a hundred proteins in eukaryotic cells carry a C-terminal CaaX box sequence, which targets them for posttranslational isoprenylation of the cysteine residue. This modification, catalyzed by either farnesyl or geranylgeranyl transferase, converts them into peripheral membrane proteins. Isoprenylation is usually followed by proteolytic cleavage of the aaX tripeptide and methylation of the carboxyl group of the newly exposed isoprenylcysteine. The C-terminal modification regulates the cellular localization and biological activity of isoprenylated proteins. We have established a strategy to produce and purify recombinant farnesylated guanylate-binding protein 1 (hGBP1), a dynamin-related large GTPase. Our system is based on the coexpression of hGBP1 with the two subunits of human farnesyltransferase in Escherichia coli and a chromatographic separation of farnesylated and unmodified protein. Farnesylated hGBP1 displays altered GTPase activity and is able to interact with liposomes in the activated state. PMID- 20348590 TI - Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles. AB - A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration. PMID- 20348591 TI - Coupling between magnetic and optical properties of stable Au-Fe solid solution nanoparticles. AB - Au-Fe nanoparticles constitute one of the simplest prototypes of a multifunctional nanomaterial that can exhibit both magnetic and optical (plasmonic) properties. This solid solution, not feasible in the bulk phase diagram in thermal equilibrium, can be formed as a nanostructure by out-of equilibrium processes. Here, the novel magnetic, optical and magneto-optical properties of ion-implanted Au-Fe solid solution nanoparticles dispersed in a SiO(2) matrix are investigated and correlated. The surface plasmon resonance of the Au-Fe nanoparticles with almost equicomposition is strongly damped when compared to pure Au and to Au-rich Au-Fe nanoparticles. In all cases, the Au atoms are magnetically polarized, as measured by x-ray magnetic circular dichroism, and ferromagnetically coupled with Fe atoms. Although the chemical stability of Au-Fe nanoparticles is larger than that of Fe nanoparticles, both the magnetic moment per Fe atom and the order temperature are smaller. These results suggest that electronic and magnetic properties are more influenced by the hybridization of the electronic bands in the Au-Fe solid solution than by size effects. On the other hand, the magneto-optical transitions allowed in the vis-nIR spectral regions are very similar. In addition, we also observe, after studying the properties of thermally treated samples, that the Au-Fe alloy is stabilized, not by surface effects, but by the combination of the out-of equilibrium nature of the ion implantation technique and by changes in the properties due to size effects. PMID- 20348592 TI - Proximity field nanopatterning of azopolymer thin films. AB - A method for inscribing surface relief gratings in azopolymer thin films via proximity field nanopatterning is reported. Azopolymers prepared by ring opening metathesis polymerization were cast as thin films and brought into conformal contact with transparent polydimethylsiloxane phase masks. Irradiation of the film surface through the phase masks induces mass transport of azopolymer that generates surface relief structures on the basis of the intensity modulation of the light by structures on the phase mask. The experimental images obtained matched well with those produced by optical simulation. A wide variety of structures could be inscribed in the film surface which depended on the molecular weight of the azopolymer and irradiation time. Control experiments conducted suggest that the process is entirely photonic and that the presence of the phase mask on the film surface did not affect the inscription process. PMID- 20348593 TI - High yield fabrication of chemically reduced graphene oxide field effect transistors by dielectrophoresis. AB - We demonstrate high yield fabrication of field effect transistors (FET) using chemically reduced graphene oxide (RGO) sheets. The RGO sheets suspended in water were assembled between prefabricated gold source and drain electrodes using ac dielectrophoresis. With the application of a backgate voltage, 60% of the devices showed p-type FET behavior, while the remaining 40% showed ambipolar behavior. After mild thermal annealing at 200 degrees C, all ambipolar RGO FET remained ambipolar with increased hole and electron mobility, while 60% of the p-type RGO devices were transformed to ambipolar. The maximum hole and electron mobilities of the devices were 4.0 and 1.5 cm(2) V( - 1) s( - 1) respectively. High yield assembly of chemically derived RGO FET will have significant impact in scaled up fabrication of graphene based nanoelectronic devices. PMID- 20348594 TI - Dependence of InGaP nanowire morphology and structure on molecular beam epitaxy growth conditions. AB - InGaP nanowires (NWs) were grown by the Au-assisted method in a gas source molecular beam epitaxy system. The dependence of InGaP composition, morphology and stacking fault density was studied with respect to group III and V impingement rate and size of the Au particle. Compositional analysis showed that the NWs had an In-rich core and a Ga-rich shell structure. The In incorporation within the NW became limited as the Au seed particle size diminished or the group III and V flux decreased. The NWs had wurtzite (WZ) crystal structure with zinc blende (ZB) segments (stacking faults). The density of the stacking faults decreased as the group III flux decreased and the group V flux increased. PMID- 20348595 TI - Self-assembled Bi interconnections produced by on-film formation of nanowires for in situ device fabrication. AB - We fabricated Bi nanowire interconnections between two pre-patterned electrodes using a combination of on-film formation of nanowires (OFF-ON) and self-assembly. Bi nanowires were found to grow laterally from a multilayer structure with a Cr (or SiO(2)) overlayer on top of a Bi thin film through thermal annealing to relieve vertically stored compressive stress. A Bi nanobridge with a diameter of 192 nm was formed between two Cr electrodes and was highly ohmic according to I-V measurements. A high transverse magnetoresistance of 123% was also observed at 300 K. Our results indicate that self-assembled lateral nanowire growth can be utilized as an easy means for fabricating a variety of nanowire devices without the use of catalysts or complex patterning processes. PMID- 20348596 TI - NC-AFM imaging of the TiO(2)(110)-(1 x 1) surface at low temperature. AB - The TiO(2)(110)-(1 x 1) surface is investigated using non-contact atomic force microscopy (nc-AFM) at 80 K. We successfully obtained a distinct type of image contrast mode which does not exhibit hydroxyl (OH) impurity defects that mostly appear in common nc-AFM images. We named the obtained distinct type of image contrast as the 'hidden mode'. The assignments of surface atomic rows in this contrast mode are not easy in the absence of defects. By recording different contrast modes in the same region of the surface, we identified the atomic rows obtained in the 'hidden mode' image contrast as bridging oxygen atoms (O(b)). The mechanism of contrast formation was attributed to tip-induced displacement of H atoms over oxygen atoms in the OH groups on the O(b) rows. This interpretation was supported by dissipation measurements. A possible candidate for the tip generating hidden-mode image contrast was interpreted to be a positively terminated tip apex with a dimer-like structure, revealing an attractive interaction with oxygen and a repulsive force on H atom sites. In addition, with a different tip state at close tip-sample distances, we were able to successfully resolve a high resolution image of the in-plane oxygen atoms. PMID- 20348597 TI - Nano-yarn carbon nanotube fiber based enzymatic glucose biosensor. AB - A novel brush-like electrode based on carbon nanotube (CNT) nano-yarn fiber has been designed for electrochemical biosensor applications and its efficacy as an enzymatic glucose biosensor demonstrated. The CNT nano-yarn fiber was spun directly from a chemical-vapor-deposition (CVD) gas flow reaction using a mixture of ethanol and acetone as the carbon source and an iron nano-catalyst. The fiber, 28 microm in diameter, was made of bundles of double walled CNTs (DWNTs) concentrically compacted into multiple layers forming a nano-porous network structure. Cyclic voltammetry study revealed a superior electrocatalytic activity for CNT fiber compared to the traditional Pt-Ir coil electrode. The electrode end tip of the CNT fiber was freeze-fractured to obtain a unique brush-like nano structure resembling a scale-down electrical 'flex', where glucose oxidase (GOx) enzyme was immobilized using glutaraldehyde crosslinking in the presence of bovine serum albumin (BSA). An outer epoxy-polyurethane (EPU) layer was used as semi-permeable membrane. The sensor function was tested against a standard reference electrode. The sensitivities, linear detection range and linearity for detecting glucose for the miniature CNT fiber electrode were better than that reported for a Pt-Ir coil electrode. Thermal annealing of the CNT fiber at 250 degrees C for 30 min prior to fabrication of the sensor resulted in a 7.5 fold increase in glucose sensitivity. The as-spun CNT fiber based glucose biosensor was shown to be stable for up to 70 days. In addition, gold coating of the electrode connecting end of the CNT fiber resulted in extending the glucose detection limit to 25 microM. To conclude, superior efficiency of CNT fiber for glucose biosensing was demonstrated compared to a traditional Pt-Ir sensor. PMID- 20348598 TI - Change in carrier type in high-k gate carbon nanotube field-effect transistors by interface fixed charges. AB - We study the phenomenon of change in carrier type in carbon nanotube field-effect transistors (CNFETs) caused by the atomic layer deposition (ALD) of a HfO(2) gate insulator. When a HfO(2) layer is deposited on a CNFET, the type of carrier changes from p-type to n-type. The so-obtained n-type device has good performance and stability in air. The conductivity of such a device with a channel length of 0.7 microm is 11% of the quantum conductance 4e(2)/h. The contact resistance for electron current is estimated to be 14 kOmega. The n-type conduction of this CNFET is maintained for more than 100 days. The change in carrier type is attributed to positive fixed charges introduced at the interface between the HfO(2) and SiO(2) layers. We also propose a novel technique to control the type of conduction by utilizing interface fixed charges; this technique is compatible with Si CMOS process technology. PMID- 20348599 TI - Hydrogen gas sensing properties of PdO thin films with nano-sized cracks. AB - We report on a novel method for the fabrication of highly sensitive hydrogen gas sensors based on palladium oxide thin films and have investigated their hydrogen sensing properties and nanostructures. To our knowledge, this is the first report on the use of palladium oxide and reduced palladium thin films as hydrogen sensors. The palladium oxide thin films were deposited on thermally oxidized Si substrates using a reactive direct current (DC) magnetron sputtering system. Considerable changes in the resistance of the palladium oxide thin films were observed when they were initially exposed to hydrogen gas, as a result of the reduction process. After the initial exposure to hydrogen gas of PdO(30%), its sensitivity increased up to approximately 4.5 x 10(3)%. The morphology of the PdO surface was analyzed using a scanning electron microscope (SEM), in order to investigate the interactions between palladium oxide and hydrogen. The SEM images showed a large number of nano-sized cracks on the surface of the palladium oxide during the reduction process, which acted to increase the effective surface-to volume ratio. The response behaviors of the reduced Pd films to hydrogen gas were reversible and had an enhanced sensing property when compared with those of the pure Pd films. In addition, their sensitivities and response times were improved due to the nano-sized cracks on the surfaces. The results demonstrate that palladium oxide and reduced palladium thin films can be applied for use in highly sensitive hydrogen sensors. PMID- 20348600 TI - Sensing individual terahertz photons. AB - One of the promising ways to perform single-photon counting of terahertz radiation consists in sensitive probing of plasma excitation in the electron gas upon photon absorption. We demonstrate the ultimate sensor operating on this principle. It is assembled from a GaAs/AlGaAs quantum dot, electron reservoir and superconducting single-electron transistor. The quantum dot is isolated from the surrounding electron reservoir in such a way that when the excited plasma wave decays, an electron could tunnel off the dot to the reservoir. The resulting charge polarization of the dot is detected with the single-electron transistor. Such a system forms an easy-to-use sensor enabling single-photon counting in a very obscure wavelength region. PMID- 20348601 TI - Tailoring two-dimensional PTCDA-melamine self-assembled architectures at room temperature by tuning molecular ratio. AB - Engineering and tuning multi-component supramolecular self-assemblies on surfaces is one of the challenges of nanotechnology. We use scanning tunneling microscopy to investigate the influence of molecular ratio on the self-assembly of PTCDA melamine structures on Au(111)-(22 x complex square root of 3). Our observations reveal that three different chiral supramolecular networks having a PTCDA:melamine ratio of 3:2, 1:2, 1:4 can be selectively created by tuning the ratio of molecules deposited on the surface. The 1:2 ratio network having melamine in excess has been observed previously but the 1:4 network has not yet been reported. In comparison, the multi-component 3:2 network having PTCDA in excess is a completely new structure. PMID- 20348602 TI - Monitoring prion protein expression in complex biological samples by SERS for diagnostic applications. AB - Surface-enhanced Raman spectroscopy (SERS) allows a new insight into the analysis of cell physiology. In this work, the difficulty of producing suitable substrates that, besides permitting the amplification of the Raman signal, do not interact with the biological material causing alteration, has been overcome by a combined method of hydrothermal green synthesis and thermal annealing. The SERS analysis of the cell membrane has been performed with special attention to the cellular prion protein PrP(C). In addition, SERS has also been used to reveal the prion protein-Cu(II) interaction in four different cell models (B104, SH-SY5Y, GN11, HeLa), expressing PrP(C) at different levels. A significant implication of the current work consists of the intriguing possibility of revealing and quantifying prion protein expression in complex biological samples by a cheap SERS-based method, replacing the expensive and time-consuming immuno-assay systems commonly employed. PMID- 20348603 TI - Titanium compacts produced by the pulvimetallurgical hydride-dehydride method for biomedical applications. AB - Titanium powder production by the hydride-dehydride method has been developed as a non-expensive process. In this work, commercially pure grade two Ti specimens were hydrogenated. The hydrided material was milled in a planetary mill. The hydrided titanium powder was dehydrided and then sieved to obtain a particle size between 37 and 125 microm in order to compare it with a commercial powder produced by chemical reduction with a particle size lower than 150 microm. Cylindrical green compacts were obtained by uniaxial pressing of the powders at 343 MPa and sintering in vacuum. The powders and the density of sintered compacts were characterized, the oxygen content was measured and in vivo tests were performed in the tibia bones of Wistar rats in order to evaluate their biocompatibility. No differences were observed between the materials which were produced either with powders obtained by the hydride-dehydride method or with commercial powders produced by chemical reduction regarding modifications in compactation, sintering and biological behaviour. PMID- 20348604 TI - Dosimetric evaluation of inspiration and expiration breath-hold for intensity modulated radiotherapy planning of non-small cell lung cancer. AB - The purpose of this study was to compare target coverage and lung tissue sparing between inspiration and expiration breath-hold intensity-modulated radiotherapy (IMRT) plans for patients with non-small cell lung cancer (NSCLC). In a prospective study, seven NSCLC patients gave written consent to undergo both moderate deep inspiration and end-expiration breath-hold computed tomography (CT), which were used to generate five-field IMRT plans. Dose was calculated with a scatter and an inhomogeneity correction algorithm. The percentage of the planning target volume (PTV) receiving 90% of the prescription dose (PTV(90)), the volume of total lung receiving >or=10 Gy (V(10)) and >or=20 Gy (V(20)) and the mean lung dose (MLD) were compared by the Student's paired t-test. Compared with the expiration plans, the mean +/- SD reductions for V(10), V(20) and MLD on the inspiration plans were 4.0 +/- 3.7% (p = 0.031), 2.5 +/- 2.3% (p = 0.028) and 1.1 +/- 0.7 Gy (p = 0.007), respectively. Conversely, a mean difference of 1.1 +/ 1.1% (p = 0.044) in PTV(90) was demonstrated in favour of expiration. When using IMRT, inspiration breath-hold can reduce the dose to normal lung tissue while expiration breath-hold can improve the target coverage. The improved lung sparing at inspiration may outweigh the modest improvements in target coverage at expiration. PMID- 20348605 TI - Time-reversal focusing in microwave hyperthermia for deep-seated tumors. AB - A fast beam-forming method for hyperthermia treatment of deep-seated tumors is described and verified. The approach is based on the time-reversal characteristics of Maxwell equations. The basic principle of the method is coupling of the electromagnetic modeling of the system with the actual application. In this modeling the wavefront of the source is propagated through a patient-specific model from a virtual antenna placed in the tumor of the model. The simulated radiated field is then captured using a computer model of the surrounding antenna system. The acquired amplitudes and phases are then used in the real antenna system. The effectiveness of this procedure is demonstrated by calculating the power absorption distribution using FDTD electromagnetic simulations of a realistic 2D breast model as well as a 2D neck model. Several design parameters, i.e. number of antennas, operating frequency and dimensions, have been evaluated by performance indicators. The promising results suggest that the development of this technique is pursued further. PMID- 20348606 TI - Investigation into the feasibility of using PRESAGE/optical-CT dosimetry for the verification of gating treatments. AB - This work presents an investigation into the use of PRESAGE dosimeters with an optical-CT scanner as a 3D dosimetry system for quantitative verification of respiratory-gated treatments. The CIRS dynamic thorax phantom was modified to incorporate a moving PRESAGE dosimeter-simulating respiration motion in the lungs. A simple AP/PA lung treatment plan was delivered three times to the phantom containing a different but geometrically identical PRESAGE insert each time. Each delivery represented a treatment scenario: static, motion (free breathing) and gated. The dose distributions, in the three dosimeters, were digitized by the optical-CT scanner. Improved optical-CT readout yielded an increased signal-to-noise ratio by a factor of 3 and decreased reconstruction artifacts compared with prior work. Independent measurements of dose distributions were obtained in the central plane using EBT film. Dose distributions were normalized to a point corresponding to the 100% isodose region prior to the measurement of dose profiles and gamma maps. These measurements were used to quantify the agreement between measured and ECLIPSE(R) dose distributions. Average gamma pass rates between PRESAGE and EBT were >99% (criteria 3% dose difference and 1.2 mm distance-to-agreement) for all three treatments. Gamma pass rates between PRESAGE and ECLIPSE(R) 3D dose distributions showed excellent agreement for the gated treatment (100% pass rate), but poor for the motion scenario (85% pass rate). This work demonstrates the feasibility of using PRESAGE/optical-CT 3D dosimetry to verify gating-enabled radiation treatments. The capability of the Varian gating system to compensate for motion in this treatment scenario was demonstrated. PMID- 20348607 TI - Delivery of two-dimensional spatially-slowly-varying intensity-modulated beams by jaws only (JO) in rotate-translate mode. AB - IMRT can be delivered by jaws only (JO) provided some compromises are accepted. In this letter it is shown how the use of a rotate-translate methodology (ROTJO), also employing only jaws, can lead to the delivery of a two-dimensional intensity modulated beam wherein the modulation is spatially slowly varying. PMID- 20348608 TI - Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns. AB - Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick et al 2008 J. Neurophysiol. 99 787-98) we investigated whether highly spatially localized stimulus-evoked cortical hemodynamics responses displayed a linear time-invariant (LTI) relationship with neural activity. Presentation of stimuli to individual whiskers of 2 s and 16 s durations produced hemodynamics and neural activity spatially localized to individual cortical columns. Two-dimensional optical imaging spectroscopy (2D-OIS) measured hemoglobin responses, while multi-laminar electrophysiology recorded neural activity. Hemoglobin responses to 2 s stimuli were deconvolved with underlying evoked neural activity to estimate impulse response functions which were then convolved with neural activity evoked by 16 s stimuli to generate predictions of hemodynamic responses. An LTI system more adequately described the temporal neuro hemodynamics coupling relationship for these spatially localized sensory stimuli than in previous studies that activated the entire whisker cortex. An inability to predict the magnitude of an initial 'peak' in the total and oxy- hemoglobin responses was alleviated when excluding responses influenced by overlying arterial components. However, this did not improve estimation of the hemodynamic responses return to baseline post-stimulus cessation. PMID- 20348609 TI - Linking computer-aided design (CAD) to Geant4-based Monte Carlo simulations for precise implementation of complex treatment head geometries. AB - Most of the treatment head components of medical linear accelerators used in radiation therapy have complex geometrical shapes. They are typically designed using computer-aided design (CAD) applications. In Monte Carlo simulations of radiotherapy beam transport through the treatment head components, the relevant beam-generating and beam-modifying devices are inserted in the simulation toolkit using geometrical approximations of these components. Depending on their complexity, such approximations may introduce errors that can be propagated throughout the simulation. This drawback can be minimized by exporting a more precise geometry of the linac components from CAD and importing it into the Monte Carlo simulation environment. We present a technique that links three-dimensional CAD drawings of the treatment head components to Geant4 Monte Carlo simulations of dose deposition. PMID- 20348610 TI - Gating characteristics of an Elekta radiotherapy treatment unit measured with three types of detector. AB - The characteristics of an Elekta Precise treatment machine with a gating interface were investigated. Three detectors were used: a Farmer ionization chamber, a MatriXX ionization chamber array and an in-house, single pulse measurement ionization chamber (IVC). Measurements were made of dosimetric accuracy, flatness and symmetry characteristics and duty cycle for a range of beam-on times and gating periods. Results were compared with a standard ungated delivery as a reference. For all beam-on times, down to 0.5 s, dosimetric differences were below +/-1% and flatness and symmetry parameter variations were below +/-1.5%. For the shorter beam-on times the in-house detector deviated from the other two detectors, suggesting that this device should be used in conjunction with other detectors for absolute dosimetry purposes. However, it was found to be useful for studying gated beam characteristics pulse by pulse. PMID- 20348611 TI - Intracranial pressure pulse morphological features improved detection of decreased cerebral blood flow. AB - We investigated whether intracranial pressure (ICP) pulse morphological metrics could be used to realize continuous detection of low cerebral blood flow. Sixty three acutely brain injured patients with ICP monitoring, daily (133)Xenon cerebral blood flow (CBF) and daily transcranial Doppler (TCD) assessments were studied. Their ICP recordings were time-aligned with the CBF and TCD measurements so that a 1 h ICP segment near the CBF and TCD measurements was obtained. Each of these recordings was processed by the Morphological Cluster and Analysis of Intracranial Pressure (MOCAIP) algorithm to extract pulse morphological metrics. Then the differential evolution algorithm was used to find the optimal combination of the metrics that provided, using the regularized linear discriminant analysis, the largest combined positive predictivity and sensitivity. At a CBF threshold of 20 ml/min/100 g, a sensitivity of 81.8 +/- 0.9% and a specificity of 50.1 +/- 0.2% were obtained using the optimal combination of conventional TCD and blood analysis metrics as input to a regularized linear classifier. However, using the optimal combination of the MOCAIP metrics alone we were able to achieve a sensitivity of 92.5 +/- 0.7% and a specificity of 84.8 +/- 0.8%. Searching the optimal combination of all available metrics, we achieved the best result that was marginally better than those from using MOCAIP alone. This study demonstrated that the potential role of ICP monitoring may be extended to provide an indicator of low global cerebral blood perfusion. PMID- 20348612 TI - The validity of tympanic and exhaled breath temperatures for core temperature measurement. AB - We examined the efficacy of tympanic (T(ty)) and exhaled breath (T(X)) temperatures as indices of rectal temperature (T(re)) by applying heat (condition A) and cold (condition B) in a dynamic A-B-A-B sequence. Fifteen healthy adults (8 men; 7 women; 24.9 +/- 4.6 years) volunteered. Following a 15 min baseline period, participants entered a water tank maintained at 42 degrees C water temperature and passively rested until their T(re) increased by 0.5 degrees C above baseline. Thereafter, they entered a different water tank maintained at 12 degrees C water temperature until their T(re) decreased by 0.5 degrees C below baseline. This procedure was repeated twice (i.e. A-B-A-B). T(ty) demonstrated moderate response delays to the repetitive changes in thermal balance, whereas T(X) and T(re) responded relatively fast. Both T(ty) and T(X) correlated significantly with T(re) (P < 0.05). Linear regression models were used to predict T(re) based on T(ty) and T(X). The predicted values from both models correlated significantly with T(re) (P < 0.05) and followed the changes in T(re) during the A-B-A-B thermal protocol. While some mean differences with T(re) were observed (P < 0.05), the 95% limits of agreement were acceptable for both models. It is concluded that the calculated models based on tympanic and exhaled breath temperature are valid indicators of core temperature. PMID- 20348613 TI - Laboratory diagnosis of HIV infection and access to HIV testing in Italy. Preface. PMID- 20348614 TI - HIV virology and pathogenetic mechanisms of infection: a brief overview. AB - Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays. PMID- 20348615 TI - The epidemic of HIV infection and AIDS, promotion of testing, and innovative strategies. AB - In Europe, the incidence of new diagnoses of HIV infection in 2008 was 86.7 cases per one million population, and most cases were attributable to sexual transmission. In Italy, in 2007, the incidence was 60.0 cases per one million population (in the areas in which surveillance exists), and 73.7% of the cases were attributable to sexual transmission. At present, there are an estimated 170,000-180,000 persons living with HIV/AIDS in Italy, some of whom are unaware of being infected. Based on available epidemiological data and taking into consideration the level of risk of exposure to HIV, we describe several proposals for promoting access to HIV testing in diverse population groups and contexts, including some innovative approaches. The promotion of HIV testing is fundamental for public health and human rights and must be associated with treatment, care and prevention activities, which must be guaranteed for the entire population. PMID- 20348616 TI - Laboratory diagnostics for HIV infection. AB - Laboratory diagnosis of human immunodeficiency virus (HIV) infection is fundamental for detecting and monitoring infection. Many diagnostic tools are available that are based on both detection of HIV-specific antibodies and virus antigen, or nucleic acid. As technology evolves, HIV testing assays are being improved providing better sensitivity and specificity. In this short review, we summarize the common and new methodologies that are being used in laboratories, from the HIV antibody-based assays to the new tests for the detection of HIV nucleic acids. PMID- 20348617 TI - Suggested strategies for the laboratory diagnosis of HIV infection in Italy. AB - HIV/AIDS surveillance data indicate that, in 2008, approximately one-fourth of all HIV infections in adults remain undiagnosed in Italy and that close to 60% of AIDS diagnosed individuals discovered their seropositivity at the diagnosis of AIDS. Late diagnosis of HIV infection is associated with increased mortality and morbidity and increased cost to healthcare services. From a public health perspective, knowledge of HIV status is associated with a reduction in risk behaviour. Thus, a routine screening for HIV infection is important for both a better prognostic outcome, and control of HIV spreading in the population. In Italy there are not shared guidelines for the laboratory diagnosis. In this paper, we suggest two algorithms that can be adopted for the diagnosis of HIV infection in individuals undergoing HIV testing. PMID- 20348618 TI - Criteria for standardising counselling for HIV testing. AB - In the present work, we outline basic health counselling skills, specifically, those for performing pre-test and post-test counselling for HIV infection. The ultimate goal is to propose that counselling be performed in facilities that carry out screening for anti-HIV antibodies, following standardised (and thus replicable) criteria, with consistent focus on the quality of the relationship between the healthcare professional and the individual undergoing testing and on the individual's specific needs. PMID- 20348619 TI - Aspects of the Italian legislation related to HIV testing. AB - Italy has adhered to international declarations regarding the prevention, care, and treatment of HIV/AIDS and has adopted the fundamental interventions for surveillance and control; access to testing is defined by Law 135 of 5 June 1990. At the time, the Ministry of Health issued decrees to define national epidemiological surveillance systems for new HIV infections. The decree provides indications on the data to be collected, data flow, the modes of data transmission respecting security measures and some recommendations regarding access to HIV testing. It is thus necessary to develop national recommendations on appropriate methods for considering the diverse phases of access to testing in relation to the level of awareness of the minor, the outcome and divulging of the test. PMID- 20348620 TI - Continued high prevalence of HIV, HBV and HCV among injecting and noninjecting drug users in Italy. AB - We estimated the prevalence of HIV, HBV and HCV infections among injecting and noninjecting drug users treated within public drug-treatment centres in Italy to determine the correlates of infection. In the sample of 1330 drug users, the prevalence of HIV was 14.4% among drug injectors and 1.6% among non-injectors; the prevalence of HBV was 70.4% among injecting drug users and 22.8% among non injectors and of HCV was 83.2% among injecting drug users and 22.0% among non injectors. Old age, unemployment, and intravenous drug use were significantly correlated with each of the infections, as well as a longer history of injecting drug use. The results indicate that these infections continue to circulate among drug users, highlighting the need for monitoring of this group in Italy. PMID- 20348621 TI - Molecular aspects of tumor cell migration and invasion. AB - Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper. PMID- 20348622 TI - Bird populations as sentinels of endocrine disrupting chemicals. AB - Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment. PMID- 20348623 TI - Application of the dangerous Preparation Directive: consequences on plant protection products in the internal market. AB - Legislative Decree March 2003, n. 65 brought about implementation of Directive 1999/45/ EC of the European Parliament and of the Council dated 31 May 1999 and Directive 2001/60/EC of the Commission dated 7 August 2001 concerning laws, regulations and administrative provisions of the Member States relating to the classification, packaging and labelling of dangerous preparations come into force. Directive 1999/45/EC brought about a series of modifications representing the new regulatory framework for dangerous preparations. The above-mentioned Decree supplies the criteria for the evaluation of hazardous preparations, regardless of their intended use, and completes previously undertaken steps, in strict connection with the analogous Directives of the EU, for the problematic complexity of the classification, packaging and labelling of dangerous substances and preparations. The applicative importance of Directive 99/45/EC derives directly from these innovations. Among these, for the first time, the category of "dangerous for the environment" has been extended also to preparations. Moreover, also for the first time, the scope of the Directive is extended to plant protection products and biocides. This paper provides an overview on the results of the hazard classification procedure carried out at national level for plant protection products in light of the new rules and the outcomes in terms of variations of the labels through comparison between previous and new classification. Furthermore the most significant issue which come up during the classification process and the criteria applied for their solution are also reported. PMID- 20348624 TI - Brief note about plasma catecholamines kinetics and submaximal exercise in untrained standardbreds. AB - Four untrained standardbred horses performed a standardized exercise test on the treadmill and an automated blood collection system programmed to obtain blood samples every 15 s was used for blood collection in order to evaluate the kinetics of adrenaline and noradrenaline. The highest average values obtained for adrenaline and noradrenaline were 15.0 +/- 3.0 and 15.8 +/- 2.8 nmol/l respectively, with exponential accumulation of adrenaline (r = 0.977) and noradrenaline (r = 0.976) during the test. Analysis of the correlation between noradrenaline and adrenaline for each phase of the test shows that correlation coefficient decreases as the intensity of exercise increases (from r = 0.909 to r = 0.788). This suggests that during submaximal exercise, the process for release, distribution and clearance of adrenaline into blood circulation differs from that of noradrenaline. PMID- 20348835 TI - The impact of a diagnosis of couple subfertility on male sexual function. AB - AIM: The aim was to study: a) the prevalence of sexual dysfunction in male partners of subfertile couples; b) the possible correlation between sexual dysfunction and seminal profile. SUBJECTS AND METHODS: Male partners (no.=171) of subfertile couples were studied, aged between 25 and 40 yr, attending the Andrology Unit of Sant'Andrea Hospital. All the subjects responded to a modified International Index of Erectile Function (IIEF) questionnaire, made up of 5 questions: 2 regarding erectile function, 1 concerning orgasmic function, 1 question on sexual desire, and 1 on satisfaction with intercourse. The questionnaire investigated both spontaneous sex for pleasure and sex intended to lead to pregnancy. The subjects underwent standard semen analysis, according to World Health Organization guidelines. RESULTS: The data showed a disorder in sexual intercourse for reproductive purposes in 37 subjects (23.7%). Of these, only 14 (8.9%) also had problems with sex for pleasure. On the other hand, there was no significant variation in the prevalence of sexual dysfunction related to seminal profile. CONCLUSIONS: A diagnosis of subfertility represents a stressful situation which can reduce the pleasure of sex, especially in intercourse intended for reproductive purposes; this disorder in sexual activity does not seem to be directly correlated with awareness of the severity of the semen alterations. PMID- 20348836 TI - Effects of somatostatin analogues on acromegalic cardiomyopathy: results from a prospective study using cardiac magnetic resonance. AB - OBJECTIVE: Left ventricular (LV) hypertrophy is the main finding of patients with active acromegaly at cardiac magnetic resonance (CMR). The aim of the study was to evaluate heart changes in acromegalic patients treated with somatostatin analogues (SMSA) using CMR. DESIGN AND PATIENTS: This was a prospective study. Fourteen consecutive patients (8 women, mean age 46+/-10 yr) with untreated active acromegaly were submitted to CMR and 2D-color Doppler echocardiography before and after a 6-month SMSA course. MEASUREMENTS: LV volume, mass (LVM) and wall thickness. RESULTS: CMR: Mean LVM and LVM index (i) decreased from 151+/-17 g and 77+/-9 g/m2, to 144+/-24 g and 70+/-12 g/m2, respectively (p=0.047 and p<0.0001, respectively); LV hypertrophy reverted in 6 out of 10 patients (p=0.016). Systolic function, evaluated by measuring LV ejection fraction remained normal in all patients (67+/-11%). There was not a correlation between changes in LVMi and changes in serum IGF-I concentrations. However, patients with controlled disease had higher reduction of LVMi than those with uncontrolled acromegaly (DeltaLVMi, -8.2+/-4.2 vs 4.0+/-5.3 p<0.05). 2D-echo cardiography: Mean LVMi decreased from 110+/-24 g/m2 to 100+/-20 g/m2 (p=0.026); hypertrophy, revealed in 5 patients (36%) at baseline, reversed in 2 patients (p=0.500) after SMSA; abnormal diastolic function [evaluated by isovolumic relaxation time or early (E) to late of atrial (A) peak velocities ratio] found in 4 patients (29%) at the study entry, improved in a patient. Systolic function remained within the normal range in all patients during the study period. CONCLUSIONS: CMR detects changes in LVMi in most patients with acromegaly treated with SMSA, which are more evident if the disease is controlled. PMID- 20348837 TI - The effect of estrogens on plasma ghrelin concentrations in women. AB - BACKGROUND: Data regarding the possible effects of estrogen on ghrelin secretion in humans are limited and contradictory. AIM: To investigate the effect of estradiol (E2) on ghrelin levels in normal pre- and post-menopausal women. SUBJECTS AND METHODS: A total of 21 women divided into 3 groups, i.e.13 normally cycling women (no.=7, group 1 and no.=6, group 2) and 8 post-menopausal women (group 3). Women of group 1 received increasing doses of E2 through skin patches from cycle days 3 to 5. Women of group 2, underwent total abdominal hysterectomy plus bilateral salpingo-oophorectomy (TAH+BSO) on cycle day 3. Women of group 3 received po increasing doses of E2 valerate for 15 days. Acylated ghrelin and E2 were measured in all blood samples. RESULTS: In group 1, plasma ghrelin levels did not show any significant changes for the week following cycle day 3. In group 2, ghrelin levels were similar before and after TAH+BSO and remained stable during the first 7 post-operative days. In group 3, no significant changes in plasma ghrelin levels were seen during the 15 days of E2 administration. CONCLUSIONS: The present study demonstrates for the first time that ghrelin values were not affected either by exogenous short-term estrogen administration to pre- and post-menopausal women or following ovariectomy in pre-menopausal women. It is suggested that ovarian hormones are not involved in the regulation of ghrelin secretion in women. PMID- 20348838 TI - Dose optimization of somatostatin analogues for acromegaly patients. PMID- 20348839 TI - Endocrinology and art. David returning triumphant with the head of Goliath. Antiveduto Grammatica (1571-1626) Rome, Italy. PMID- 20348840 TI - HIF-2alpha: many cancers, one engine? PMID- 20348841 TI - Fine-tuning the DNA damage response: protein phosphatase 2A checks on CHK2. PMID- 20348842 TI - Protein phosphatases and the dynamics of the DNA damage response. PMID- 20348843 TI - Freezing Polo in its sleep: targeting the inactive conformation of Polo-like kinase 1 in cancer cells. PMID- 20348844 TI - Mitochondrial targeting signals: another barcode in p14ARF? PMID- 20348845 TI - p53 and Mdm2: an auld alliance. PMID- 20348846 TI - Cryptic mitochondrial targeting signals in human ARF: clues to controlling cancer? PMID- 20348847 TI - The archaeal cell cycle: clues from comparative genomics. PMID- 20348848 TI - Cell cycle regulated genes in the three domains of life. PMID- 20348850 TI - Skip the nucleus, AKT drives Skp2 and FOXO1 to the same place? PMID- 20348849 TI - mTOR goes to the nucleus. PMID- 20348851 TI - Biologic and experimental variation of measured cancer stem cells. AB - Whereas it has become clear that measured stem cell frequencies in tumors greatly depend on the assay system used, the research focus now shifts towards identification of the biologic variability of cancer stem cells in different disease subsets. In a recent study we quantified the frequency and in vitro expansion potential of leukemia initiating cells in a murine model of acute myeloid leukemia driven either by retroviral overexpression of MN1 and a control vector, or by MN1 and a HOX gene through limiting dilution transplantation assays in syngeneic mice. Both leukemia-initiating cell frequency and expansion potential were increased by over two orders of magnitude in the two-oncogene compared to the one-oncogene model, documenting the functional heterogeneity of leukemia-initiating cells. Loss-of-function studies showed that STAT5b and STAT1 are critical for the enhanced self-renewal activity. Here we discuss implications of our findings and potential sources of experimental variability of measured leukemia or cancer stem cell frequencies. PMID- 20348853 TI - Skin cancers affecting the eyelids, periocular, and periorbital areas of the face. Preface. PMID- 20348854 TI - Eyelid and periorbital skin basal cell carcinoma: oculoplastic management and surgery. PMID- 20348855 TI - Squamous cell carcinoma of eyelid, periocular, and periorbital skin. PMID- 20348856 TI - Eyelid and periorbital cutaneous malignant melanoma. PMID- 20348857 TI - Sebaceous adenocarcinoma of the eyelid. PMID- 20348858 TI - Eyelid and periocular cutaneous Merkel cell carcinoma (aka. neuroendocrine or trabecular carcinoma). PMID- 20348859 TI - Unusual eyelid, periocular, and periorbital cutaneous malignancies. PMID- 20348860 TI - Outcomes of excision of 1750 eyelid and periocular skin basal cell and squamous cell carcinomas by modified en face frozen section margin-controlled technique. PMID- 20348861 TI - Mohs micrographic surgery for eyelid and periorbital skin cancer. PMID- 20348862 TI - Oculoplastic surgery for lower eyelid reconstruction after periocular cutaneous carcinoma. PMID- 20348863 TI - Oculoplastic surgery for upper eyelid reconstruction after cutaneous carcinoma. PMID- 20348864 TI - A systematic approach to the oculoplastic reconstruction of the eyelid medial canthal region after cancer excision. PMID- 20348865 TI - Lateral canthal reconstruction after head-neck or periocular cutaneous malignancy: oculoplastic and facial plastic surgery techniques. PMID- 20348866 TI - Lacrimal reconstruction after removal of eyelid or periocular cutaneous cancer. PMID- 20348867 TI - Orbital spread of eyelid and periocular cutaneous cancer. PMID- 20348868 TI - Reconstruction of large and complex periorbital defects from cutaneous cancer. PMID- 20348870 TI - Primary human bronchial epithelial cells grown from explants. AB - Human bronchial epithelial cells are needed for cell models of disease and to investigate the effect of excipients and pharmacologic agents on the function and structure of human epithelial cells. Here we describe in detail the method of growing bronchial epithelial cells from bronchial airway tissue that is harvested by the surgeon at the times of lung surgery (e.g. lung cancer or lung volume reduction surgery). With ethics approval and informed consent, the surgeon takes what is needed for pathology and provides us with a bronchial portion that is remote from the diseased areas. The tissue is then used as a source of explants that can be used for growing primary bronchial epithelial cells in culture. Bronchial segments about 0.5-1cm long and < or =1cm in diameter are rinsed with cold EBSS and excess parenchymal tissue is removed. Segments are cut open and minced into 2-3mm(3) pieces of tissue. The pieces are used as a source of primary cells. After coating 100mm culture plates for 1-2 hr with a combination of collagen (30 microg/ml), fibronectin (10 microg/ml), and BSA (10 microg/ml), the plates are scratched in 4-5 areas and tissue pieces are placed in the scratched areas, then culture medium (DMEM/Ham F-12 with additives) suitable for epithelial cell growth is added and plates are placed in an incubator at 37 degrees C in 5% CO(2) humidified air. The culture medium is changed every 3-4 days. The epithelial cells grow from the pieces forming about 1.5 cm diameter rings in 3-4 weeks. Explants can be re-used up to 6 times by moving them into new pre-coated plates. Cells are lifted using trypsin/EDTA, pooled, counted, and re-plated in T75 Cell Bind flasks to increase their numbers. T75 flasks seeded with 2-3 million cells grow to 80% confluence in 4 weeks. Expanded primary human epithelial cells can be cultured and allowed to differentiate on air-liquid interface. Methods described here provide an abundant source of human bronchial epithelial cells from freshly isolated tissues and allow for studying these cells as models of disease and for pharmacology and toxicology screening. PMID- 20348871 TI - Digital technology in cardiac care. PMID- 20348873 TI - Arrhythmias: Catheter ablation for prevention of ventricular tachycardia. PMID- 20348874 TI - Heart failure: Telephone monitoring improves outcomes in patients with CHF. PMID- 20348875 TI - Heart failure: Continuous-flow LVADs improve clinical outcomes. PMID- 20348876 TI - Antisense HIF-1alpha prevents acquired tumor resistance to angiostatin gene therapy. AB - Angiostatin is a naturally occurring inhibitor of angiogenesis that is being developed as a drug to fight cancer. In this study we reveal that EL-4 tumors established in mice rapidly develop resistance to angiostatin gene therapy by upregulating hypoxia-inducible pathways. Angiostatin initially delayed tumor growth for 6 days by reducing blood vessel density. However, tumors quickly responded by upregulating the production of hypoxia-inducible factor-1alpha (HIF 1alpha) and its effector vascular endothelial growth factor (VEGF) in response to increasing tumor hypoxia, leading to restored angiogenesis and rapid tumor growth. Theoretically, blockade of HIF-1 should prevent resistance to anti angiogenic therapy by preventing a tumor from responding to induced hypoxia. Antisense HIF-1alpha inhibited the expression of HIF-1alpha and of the HIF-1 effectors VEGF, glucose transporter-1 and lactate dehydrogenase. As a monotherapy, it was effective in eradicating small 0.1 cm diameter tumors, but only delayed the growth of large 0.4 cm diameter tumors. In contrast, timed injection of a combination of angiostatin and antisense HIF-1alpha plasmids completely eradicated large EL-4 tumors within 2 weeks, and prevented upregulation of hypoxia-inducible pathways induced by angiostatin. The data indicate that blocking hypoxia-inducible pathways by antisense HIF-1alpha can circumvent hypoxia-induced drug resistance and thereby augment the efficacy of anti-angiogenic therapies. PMID- 20348877 TI - Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. AB - Multilocular cystic renal cell carcinoma is an uncommon low grade renal cell carcinoma with unique morphologic features. Its cytogenetic characteristics have not been fully investigated. Its relationship to typical clear cell renal cell carcinoma is uncertain. We evaluated 19 cases of multilocular cystic renal cell carcinoma diagnosed by strict morphologic criteria using the 2004 WHO classification system. The control group consisted of 19 low grade (Fuhrman grades 1 or 2) clear cell renal cell carcinomas. Chromosome 3p deletion status was determined by dual color interphase fluorescence in situ hybridization analysis. Chromosome 3p deletion was identified in 17 out of 19 (89%) of the clear cell renal cell carcinoma cases and 14 out of 19 (74%) of the multilocular cystic renal cell carcinoma cases, respectively. There was no difference in the status of chromosome 3p deletion between clear cell renal cell carcinoma and multilocular cystic renal cell carcinoma (P=0.40). These results support the concept that multilocular cystic renal cell carcinoma as a subtype of clear cell renal cell carcinoma. PMID- 20348878 TI - Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas. AB - Rearrangement of MYC with immunoglobulin genes is a hallmark of Burkitt lymphoma. However, this rearrangement is not entirely specific and is often accompanied by varying numbers of additional cytogenetic abnormalities. This study aimed to assess the impact of karyotypic complexity, in correlation with comprehensive immunophenotypic analyses on the diagnosis and clinical outcomes of 34 cases of MYC-IG rearranged lymphomas that included Burkitt lymphoma (twenty-two cases), diffuse large B-cell lymphoma (three cases), unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (six cases), and plasmablastic lymphoma (three cases). Additional cytogenetic abnormalities were observed in 26 of 34 cases (76%), including four cases (12%) that harbored dual translocations involving BCL-2 or BCl-6. Burkitt lymphoma cases had a significantly lower number of additional abnormalities (mean of 1.7), compared with unclassified B-cell lymphoma (3.3), diffuse large B-cell lymphoma (21.7), and plasmablastic lymphoma (6.7). Cases with simple karyotype (< or =2 additional abnormalities) were more likely to have a diagnosis of Burkitt lymphoma (89 versus 33% in patients with >2 additional abnormalities, P<0.01) and express bcl-6 (95 versus 47%, P<0.01). In addition, Burkitt lymphoma, bcl-6 expression, and simple karyotype were individual predictors of better overall survival. However, in multivariate analyses, only bcl-6 expression remained an independent predictor, although survival could be further stratified by karyotypic complexity in bcl-6(+) patients. We conclude that simple karyotype and bcl-6 expression suggest a diagnosis of Burkitt lymphoma and may portend better overall survival. These results may be very useful in the diagnosis and stratification of MYC-IG rearranged high-grade B-cell lymphomas. PMID- 20348879 TI - Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin. AB - Identification of the tissue of origin of a tumor is vital to its management. Previous studies showed tissue-specific expression patterns of microRNA and suggested that microRNA profiling would be useful in addressing this diagnostic challenge. MicroRNAs are well preserved in formalin-fixed, paraffin-embedded (FFPE) samples, further supporting this approach. To develop a standardized assay for identification of the tissue origin of FFPE tumor samples, we used microarray data from 504 tumor samples to select a shortlist of 104 microRNA biomarker candidates. These 104 microRNAs were profiled by proprietary quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on 356 FFPE tumor samples. A total of 48 microRNAs were chosen from this list of candidates and used to train a classifier. We developed a clinical test for the identification of the tumor tissue of origin based on a standardized protocol and defined the classification criteria. The test measures expression levels of 48 microRNAs by qRT-PCR, and predicts the tissue of origin among 25 possible classes, corresponding to 17 distinct tissues and organs. The biologically motivated classifier combines the predictions generated by a binary decision tree and K-nearest neighbors (KNN). The classifier was validated on an independent, blinded set of 204 FFPE tumor samples, including nearly 100 metastatic tumor samples. The test predictions correctly identified the reference diagnosis in 85% of the cases. In 66% of the cases the two algorithm predictions (tree and KNN) agreed on a single-tissue origin, which was identical to the reference diagnosis in 90% of cases. Thus, a qRT-PCR test based on the expression profile of 48 tissue-specific microRNAs allows accurate identification of the tumor tissue of origin. PMID- 20348880 TI - Notch1 in primary effusion lymphoma: a clinicopathological study. AB - Primary effusion lymphoma is a human herpes virus 8 (HHV-8)-associated large cell lymphoma of body cavities. Detailed large-scale clinicopathological studies are rarely reported, and the underlying mechanism of lymphomagenesis remains elusive. In the present report, we studied the clinicodemographic, immunophenotypic, and cytomorphological features on a cohort of 12 cases of primary effusion lymphoma. In contrast to HHV-8, which was positive in all nine cases tested (100%), HIV was found in 75% (9/12) of cases, whereas the three HIV-negative cases were either in elderly patients (one with hepatitis C virus infection and one with asbestoses exposure) or in a heart transplantation recipient. By flow cytometry, the antigens expressed in descending order were CD38, CD71, HLA-DR, CD30, and CD45RO. B-cell markers were largely negative. Cytomorphologically, all cases showed atypical to anaplastic morphology. Notch1, a member of transmembrane signal transduction family, was found in six of seven HHV-8-positive cases (86%). In agreement with in vitro studies using human primary effusion lymphoma cell lines, we have found that Notch1 was expressed in the majority of HHV-8-positive primary effusion lymphoma cases, corroborating the notion that Notch1 may have an important role in HHV-8-mediated lymphomagenesis of primary effusion lymphoma. PMID- 20348881 TI - Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell. AB - The survival of osteosarcoma patients is connected to metastasis. The ezrin expression is associated with the development of metastasis and poor outcome in osteosarcoma. Ezrin is present in the cytoplasm and after phosphorylation assumes an active form and links F-actin to the cell membrane. This study evaluated ezrin and phosphorylated ezrin at site Tyr354 and Thr567 expression and its subcellular localization in osteosarcoma. We studied 50 osteosarcoma patients (mean follow-up 9.8 years). Ezrin expression was assessed using immunohistochemical and immunofluorescence analysis on tissue microarray and cultured cells of human osteosarcoma 143B. The western blot analysis was carried out on cultured cells. The majority of osteosarcomas, showing cytoplasmic positivity for ezrin, phosphorylated and unphosphorylated, were associated with membranous and nuclear positivity for phosphorylated ezrin Thr567 and phosphorylated ezrin Tyr354, respectively. Ezrin expression was associated with high-grade osteosarcoma (P=0.04), with metastasis (P=0.04) and with tumors that developed metastasis (P=0.04); phosphorylated ezrin Thr567 expression was present mostly in tumors with metastasis (P=0.01) and in osteosarcomas that did not develop metastasis (P=0.002). The osteosarcoma patients with ezrin expression have a short survival. The cytoplasmic ezrin expression in osteosarcoma matches its role of membrane cytoskeleton linker protein. The subcellular trafficking of ezrin is not blocked and it is linked to ezrin phosphorylation, also in cancer. The phosphorylated ezrin Tyr354 nuclear localization suggests its possible role as a nuclear factor in osteosarcoma. The phosphorylated ezrin Thr567 phosphorylation may not be necessary in osteosarcoma metastatic progression but it was modulated. The ezrin expression is associated with more aggressive osteosarcomas and with metastasis. PMID- 20348882 TI - Plasmablastic lymphoma with MYC translocation: evidence for a common pathway in the generation of plasmablastic features. AB - Plasmablastic lymphoma, which is considered a subtype of diffuse large B-cell lymphoma, shares many similar morphological and immunophenotypic features with plasmablastic transformation of plasma cell myeloma. In the setting of human immunodeficiency virus (HIV) infection, both types of neoplasms can be associated with Epstein-Barr virus (EBV), thus making their distinction challenging. Moreover, the biological relationship between these entities remains unclear. We report four unique cases of plasmablastic lymphoma occurring in the setting of HIV infection that had overlapping clinical and genetic features with plasma cell myeloma. We reviewed the clinical, morphological, and cytogenetic findings and performed immunohistochemistry, in situ hybridization for EBV, chromosome analysis, and fluorescent in situ hybridization (FISH) using the MYC break-apart rearrangement probe. All patients were males with a median age of 45 years. In addition to extra-nodal disease, plasmablastic morphology, and phenotype typical of plasmablastic lymphoma, three of the four cases also showed clinical findings overlapping with plasma cell myeloma, that is, monoclonal serum immunoglobulin and lytic bone lesions. Furthermore, these cases showed complex cytogenetic changes that are more commonly observed in plasma cell myeloma. A unique feature was the presence of MYC (8q24.1) rearrangement confirmed by FISH in all four cases. MYC translocation has been associated with tumor progression in multiple myeloma but has only rarely been previously reported in plasmablastic lymphoma. These cases show a clinical and biological relationship between plasmablastic lymphoma and the plasmablastic variant of plasma cell myeloma. Dysregulation of MYC may be a common genetic mechanism that imparts plasmablastic morphology and aggressive clinical course to B-cell neoplasms at a later stage of differentiation. PMID- 20348883 TI - Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements. AB - Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy. Improved treatments, including targeted therapy, require understanding the biology of these neoplasms. We therefore analyzed the morphologic, immunohistochemical and molecular biologic features of 14 PNETs from 14 patients with concurrent or previous testicular germ cell tumors; 12 tumors were from metastatic sites and 2 were primary in the testis. Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like). Immunostains directed against INI1, CD57, S-100 protein, NeuN, WT1, neurofilament, CD99, GFAP, synaptophysin, chromogranin, AE1/AE3 cytokeratin, Fli-1 and collagen IV were performed for each case. INI1 was diffusely and strongly positive in all tumors whereas the other stains, except for cytoplasmic WT1 (which showed substantial reactivity in most tumors), were mostly focal to negative, including CD99 (eight negative, six focal) and Fli-1 (all negative). The most consistently reactive 'neuroendocrine' marker was CD57. Each case was also analyzed for chromosome 22 rearrangements using a FISH-based break-apart probe method. Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET. We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs. Future treatment strategies should take these findings into account. PMID- 20348884 TI - The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. AB - Acute chorioamnionitis is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathological significance of chronic chorioamnionitis is unclear. This study was conducted to determine the frequency and severity of chronic chorioamnionitis in normal pregnancy and in various pregnancy complications. Placentas from the following patient groups were studied: (1) term not in labor (n=100), (2) term in labor (n=100), (3) preterm labor (n=100), (4) preterm prelabor rupture of membranes (n=100), (5) preeclampsia at term (n=100), (6) preterm preeclampsia (n=100), and (7) small-for gestational-age at term (n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed using real-time quantitative reverse transcription-PCR. The frequency of chronic chorioamnionitis in the preterm labor group and the preterm prelabor rupture of membranes group was 34 and 39%, respectively, which was higher than that of normal-term placentas (term not in labor, 19%; term in labor, 8%; P<0.05 each). The frequency of chronic chorioamnionitis in the preeclampsia at term group, preterm preeclampsia group, and small-for-gestational age group was 23, 16, and 13%, respectively. Concomitant villitis of unknown etiology was found in 38 and 36% of preterm labor cases and preterm prelabor rupture of membranes cases with chronic chorioamnionitis, respectively. Interestingly, the median gestational age of preterm chronic chorioamnionitis cases was higher than that of acute chorioamnionitis cases (P<0.05). The median amniotic fluid CXCL10 concentration was higher in cases with chronic chorioamnionitis than in those without, in both the preterm labor group and preterm prelabor rupture of membranes group (P<0.05 and P<0.01, respectively). CXCL9, CXCL10, and CXCL11 mRNA expression in the chorioamniotic membranes was also higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis (P<0.05). We propose that chronic chorioamnionitis defines a common placental pathological lesion among the preterm labor and preterm prelabor rupture of membranes groups, especially in cases of late preterm birth. Its association with villitis of unknown etiology and the chemokine profile in amniotic fluid suggests an immunological origin, akin to transplantation rejection and graft-versus-host disease in the chorioamniotic membranes. PMID- 20348885 TI - Risk-benefit of fluoride toothpaste. PMID- 20348886 TI - Which filling material is best in the primary dentition? AB - DATA SOURCES: The Cochrane Oral Health Group's specialised trial register (Cochrane Central Register of Controlled Trials) was searched along with Medline, Embase and the System for Information on Grey Literature in Europe, along with proceedings from conferences on early childhood caries, restorative materials for paediatric dentistry, and material sciences conferences for dental materials used for children's dentistry. There were no language restrictions. Additionally, the reference lists from articles of eligible papers were searched, and handsearches made of the journals Operative Dentistry, Journal of Restorative Dentistry, Pediatric Dentistry, Journal of Clinical Pediatric Dentistry, and the International Journal of Paediatric Dentistry. Authors and manufacturers of dental materials were individually contacted. STUDY SELECTION: Randomised controlled trials (RCT) or quasi-RCT with a minimum period of 6 months' followup were included. Both parallel group and split-mouth study designs were considered. The unit of randomisation could be the individual, group (school, school class, etc), tooth or tooth pair. Included studies had a dropout rate of less than 30%. The eligible trials consisted of young children (children aged less than 12 years) with tooth decay involving at least one tooth in the primary dentition which was symptomatic or symptom-free at the start of the study. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted, in duplicate, by two review authors. Disagreements were resolved by consultation with a third review author. Authors were contacted for missing or unclear information regarding randomisation, allocation sequence, presentation of data, etc. A quality assessment of included trials was undertaken. The Cochrane Collaboration statistical guidelines were followed for data analysis. RESULTS: Only three studies were included in this review. One study assessed the clinical performance of aesthetic crowns versus conventional stainless steel crowns in 11 children who had at least two mandibular primary molars that required a crown restoration. The outcomes assessed at 6 months included gingival health restoration failure occlusion, proximal contact and marginal integrity. The second (split-mouth) study compared a resin-modified glass ionomer with amalgam over a 36-month period. Forty pairs of Class II restorations were placed in 40 patients (21 males and 19 females; mean age 8 years +/-1.17 years). Although the study period was 36 months, only the 6- and 12-month results are reported because of the loss to followup of patients being greater than 30% for the 24- and 36-month data. The third study recruited 30 patients (age range, 4-9 years) with one pair of primary molars that required a Class II restoration. The materials tested were a compomer and amalgam. Loss to followup at 24 and 36 months was 20% and 43% respectively. This meant that only the 24-month data were usable. For all of the outcomes compared in all three studies, there were no significant differences in clinical performance between the materials tested. No studies were found that compared restorations with extractions or with no treatment as an intervention in children with childhood caries. CONCLUSIONS: It was disappointing that only three trials that compared three different types of materials were suitable for inclusion into this review. There were no significant differences found in all three trials for all of the outcomes assessed. Well-designed RCT comparing the different types of filling materials for similar outcomes are urgently needed in dentistry. There was insufficient evidence from the three included trials to make any recommendations about which filling material to use. PMID- 20348887 TI - Fluoride toothpaste prevents caries in children and adolescents at fluoride concentrations of 1000 ppm and above. AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases were searched. Previously published systematic reviews of fluoride toothpastes were also screened to identify any reports that met the inclusion criteria. In addition, the trials database at www.controlled-trials.com/ and the meta Register of Controlled Trials (www.controlledtrials.com) were searched to identify any ongoing studies of relevance. STUDY SELECTION: Randomised controlled trials (RCT) and cluster-RCT that compared fluoride toothpaste with placebo or fluoride toothpaste of a different concentration in children of up to 16 years of age, with a followup period of at least 1 year, were included. DATA EXTRACTION AND SYNTHESIS: Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were resolved by discussion and consensus or by a third party. The primary effect measure was the prevented fraction (PF, the caries increment of the control group minus the caries increment of the treatment group, expressed as a proportion of the caries increment in the control group). Where it was appropriate to pool data, network meta-analysis, network meta-regression or meta analysis models were used. Potential sources of heterogeneity were specified a priori and examined through random-effects metaregression analysis where appropriate. RESULTS: From 535 studies found, 75 were included. From these, 71 studies (79 trials) contributed data to the network meta-analysis, network metaregression or meta-analysis. For the 66 studies (74 trials) that contributed to the network meta-analysis of decayed, missing or filled surfaces [D(M)FS] in the mixed or permanent dentition, the caries preventive effect of fluoride toothpaste increased significantly with higher fluoride concentrations, with a D(M)FS PF compared with placebo of 23% [95% credible interval (CrI), 19-27%] for 1000/ 1055/ 1100/ 1250 ppm concentrations, rising to 36% (95% CrI, 27-44%) for toothpastes with a concentration of 2400/ 2500/ 2800 ppm. Concentrations of 440/ 500/ 550 ppm and below showed no statistically significant effect when compared to placebo.There is some evidence of a dose-response relationship in that the PF increased as the fluoride concentration increased from the baseline although this was not always statistically significant. The effect of fluoride toothpaste also increased with baseline level of D(M)FS and supervised brushing, though this did not reach statistical significance. Six studies assessed the effects of fluoride concentrations on the deciduous dentition with equivocal results dependent upon the fluoride concentrations compared and the outcome measure. Compliance with treatment regimen and unwanted effects was assessed in only a minority of studies. When reported, no differential compliance was observed and unwanted effects such as soft tissue damage and tooth staining were minimal. CONCLUSIONS: This review confirms the benefits of using fluoride toothpaste in preventing caries in children and adolescents compared with placebo, but only statistically significantly at fluoride concentrations of 1000 ppm and above. The relative caries preventive effects of fluoride toothpastes of different concentrations increase with higher fluoride concentration. The decision of what fluoride levels to use for children aged under 6 years should be balanced with the risk of fluorosis. PMID- 20348888 TI - Using a fluoridated supplement with a high fluoride concentration in children aged under 6 years may increase the risk of fluorosis. AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, BIOSIS, Dissertation Abstracts and LILACS/BBO databases were searched. Also, reference lists from relevant articles and five journals (Community Dentistry and Oral Epidemiology, Caries Research, Journal of Dental Research, British Dental Journal, Journal of Public Health Dentistry) were searched by hand, and experts in the field of preventive dentistry and oral epidemiology contacted. STUDY SELECTION: Studies [randomised controlled trials (RCT), quasi-RCT, cohort studies, case-control studies and cross-sectional surveys] were selected if they had included children under the age of 6 years when topical fluorides were administered, and in which fluoride toothpastes, mouthrinses, gels, foams, paint-on solutions and varnishes were compared with an alternative fluoride treatment, placebo or no intervention group. DATA EXTRACTION AND SYNTHESIS: Data from all selected studies were extracted by two review authors. Risk ratios (RR) for controlled, prospective studies and odds ratios (OR) for case-control studies or cross-sectional surveys were extracted or calculated. Where both adjusted and unadjusted risk ratios or OR were presented, the adjusted value was included in the meta-analysis. RESULTS: From 3573 identified papers, 25 studies were included: two RCT, one cohort study, six case-control studies and 16 cross-sectional surveys. Only one RCT was judged to be at low risk of bias. The other RCT and all observational studies were judged to be at moderate to high risk of bias. Studies were included in four intervention/ exposure comparisons. A statistically significant reduction in fluorosis was found if brushing of a child's teeth with fluoride toothpaste commenced after the age of 12 months [OR, 0.70; random-effects 95% confidence interval (CI) for topical fluoride, 0.57-0.88; data from observational studies]. Inconsistent but statistically significant associations were found between occurrence of fluorosis and starting use of fluoride toothpaste/ toothbrushing before or after the age of 24 months (data from observational studies). From the RCT, use of higher concentrations of fluoride was associated with an increased risk of fluorosis. No significant association between the frequency of toothbrushing or the amount of fluoride toothpaste used and fluorosis was found. CONCLUSIONS: There should be a balanced consideration of the benefits of topical fluorides in caries prevention and the risk of the development of fluorosis. Most of the available evidence focuses on mild fluorosis. There is weak unreliable evidence that starting the use of fluoride toothpaste in children aged <12 months may be associated with an increased risk of fluorosis. The evidence if use begins between the age of 12 and 24 months is equivocal. If the risk of fluorosis is of concern, the fluoride level of toothpaste for young children (under 6 years of age) is recommended to be lower than 1000 parts per million (ppm). More evidence from studies with low risk of bias is needed. Future trials assessing the effectiveness of different types of topical fluorides (including toothpastes, gels, varnishes and mouthrinses) or different concentrations or both should ensure that they include an adequate followup period in order to collect data on potential fluorosis. As it is unethical to propose RCT to assess fluorosis itself, further observational studies will necessarily be undertaken in this area. Attention does, however, need to be given to the choice of study design, bearing in mind that prospective, controlled studies will be less susceptible to bias than retrospective and/ or uncontrolled studies. PMID- 20348889 TI - Glass ionomer and resin-based fissure sealants - equally effective? AB - DATA SOURCES: Studies were sourced using Biomed Central, Cochrane Oral Health Reviews, the Cochrane Library, Directory of Open Access Journals, Expanded ASAP Plus, the MetaRegister of Controlled Trials (www.controlled-trials.com/), Medline (PubMed) Science-Direct, Research Findings Electronic Register, and BBO/LILACS. STUDY SELECTION: Clinical trials and systematic reviews relevant to the review objective published in English, German, Portuguese or Spanish were included after independent review by two reviewers; disagreements were resolved by discussion and consensus. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment was undertaken independently in duplicate by two reviewers. The outcome measure for the caries preventive effect was caries-absence on sealed teeth. A meta-analysis was conducted. RESULTS: Out of 25 selected studies, 11 met the inclusion criteria (eight were trials and three were systematic reviews) with six of these being included in a meta-analysis. The pooled odds ratio was 0.96 (95% confidence interval, 0.62-1.49), indicating no difference in the caries preventive effect of glass ionomer cements (GIC) and resin-based fissure sealant material. CONCLUSIONS: GIC and resin-based sealants exhibited significant caries preventive effects. This review found no evidence that either material was superior to the other in the prevention of caries. Therefore both materials appear to be equally suitable as fissure sealant materials. PMID- 20348890 TI - Casein phosphopeptide-amorphous calcium phosphate shows promise for preventing caries. AB - DATA SOURCES: To find studies to include in the review, searches were made using Biomed Central, Cochrane Oral Health Reviews, Cochrane Library, the Directory of Open Access Journals, PubMed, Science Direct and the Research Findings Electronic Register. STUDY SELECTION: English language clinical trials [randomised clinical trials (RCT) or quasi-RCT; in situ or in vivo] or systematic reviews (with or without meta-analysis) of published trials were selected that reported on the efficacy of phosphopeptide-amorphous calcium phosphate (CPP-ACP) using any mode of delivery. Studies were reviewed and their quality assessed independently. DATA EXTRACTION AND SYNTHESIS: Data was extracted by two reviewers independently. Trials that were considered clinically and methodologically homogenous and that reported on similar outcomes were pooled for meta-analyses. RESULTS: Twelve articles were included of which five in-situ RCT could be pooled for meta analyses. The pooled in-situ results showed a weighted mean difference (WMD) of the percentage remineralisation scores in favour of chewing gum with 18.8 mg CPP ACP, compared with chewing gum without CPP-ACP of -8.01 [95% confidence interval (CI), -10.54- -5.48; P 0.00001], and compared with no intervention of -13.56 (95% CI, -16.49- -10.62; P 0.00001). A significantly higher remineralisation effect was also observed after exposure to 10.0 mg CPP-ACP (WMD, -7.75; 95% CI, -9.84- 5.66; P 0.00001). One long-term in vivo RCT (24 months) with a large sample size (N = 2720) found that the odds of a tooth surface's progressing to caries was 18% less in subjects who chewed sugar-free gum containing 54 mg CPP-ACP than in control subjects who chewed gum without CPP-ACP (P 0.03). CONCLUSIONS: Within the limitations of this systematic review with meta-analysis, the results of the clinical in-situ trials indicate a short-term remineralisation effect of CPP-ACP. Additionally, the promising in-vivo RCT results suggest a caries-preventing effect for long-term clinical CPP-ACP use. Further RCT are needed in order to confirm these initial results in vivo. PMID- 20348891 TI - Motivational interviewing may be effective in dental setting. AB - DATA SOURCES: Medline, PsychInfo, Cinahl, ERIC and the Cochrane Library were searched to identify relevant studies. STUDY SELECTION: Study quality was assessed using a scheme combining the Type of Evidence Schema, the Health Gains Notation framework and the Cochrane Health Promotion and Public Health Field quality assessment screening questions for qualitative studies, quantitative studies and systematic reviews. DATA EXTRACTION AND SYNTHESIS: A qualitative synthesis was presented. RESULTS: Thirty-two studies were identified, nine of clinical prevention and health education, three of counselling, nine of models based interventions and 11 of motivational interviewing. Motivational interviewing interventions were found to be the most effective method for altering health behaviours in a clinical setting. CONCLUSIONS: There is a need to develop an effective model for chairside oral health promotion that incorporates this evidence and allows oral health professionals to focus more on the underlying social determinants of oral disease during the clinical encounter. There is potential to further develop the motivational interviewing approach within the oral health field. PMID- 20348892 TI - Motivational interviewing in an oral health promotion programme. AB - DESIGN: This was a randomised controlled trial (RCT). INTERVENTION: From a group of patients with mental health problems participants in the motivational interviewing (MI) arm received a brief MI session (15-20 min) conducted by a doctoral psychology student trained in MI, prior to an oral health education session which was focused on exploring advantages and disadvantages, motivation and confidence, and personal values related to daily toothbrushing and oral health. All participants received two pamphlets summarising the information from the education session, instruction in using a mechanical toothbrush, a reminder system, and weekly telephone calls (for 4 weeks). OUTCOME MEASURE: Plaque scores, oral health knowledge and self-regulation were assessed at baseline and at 4 and 8 weeks. RESULTS: Sixty participants consented, and 56 (93%) completed the study. Those who did not complete the study discontinued for personal reasons (eg, moving, hospitalisation). Repeated-measures analysis of variance showed improvement (P <0.05) in plaque levels, autonomous regulation and oral health knowledge over time for both groups. Individuals receiving MI improved significantly more, however, compared with people receiving oral health education alone. CONCLUSIONS: Results suggest that MI is effective at enhancing short-term oral health behaviour change for people with severe mental illness and may be useful for the general population. PMID- 20348893 TI - Is routine dental prophylaxis effective? AB - DATA SOURCES: Searches were made for relevant papers using Medline, CINHAL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic reviews, Database of Abstracts of Reviews of Effects, Embase, Health and Psychosocial Instruments, HealthSTAR, International Pharmaceutical Abstracts, and ACP (American College of Physicians) Journal Club. Further articles were identified by reviewing the references and bibliographies of the retrieved articles. STUDY SELECTION: Articles were limited to original human studies assessing rubber cup dental prophylaxis. All other studies, including in vitro studies, reviews and case series, were excluded. Only studies in English with prophylaxis given at a recall appointment at intervals of 4 months were included. DATA EXTRACTION AND SYNTHESIS: The quality of articles was assessed independently and evidence levels rated. A qualitative synthesis is presented. RESULTS: Four articles relating to dental prophylaxis and caries prevention and two articles relating to dental prophylaxis and gingivitis prevention were included. Four studies found that a dental prophylaxis was not warranted before professionally applied topical fluoride (PATF) for caries prevention in children. A generalisation about dental prophylaxis before PATF cannot be applied to adolescents and adults. Available evidence from two other studies fails to demonstrate any benefit in the prevention of gingivitis from further dental prophylaxis at the interval used here for recall examinations. CONCLUSIONS: To prevent caries in children, dental prophylaxis need not be provided either at a recall visit or before PATF. Dental prophylaxis at intervals of 4 months or more is not justified for the prevention of gingivitis in the general population. PMID- 20348894 TI - Periodontal treatment did not prevent complications of pregnancy. AB - DESIGN: A randomised controlled trial (RCT) was conducted. INTERVENTION: Women found to have a periodontal disease were randomly allocated to receive periodontal treatment in midpregnancy (this was the treatment group; n = 542) or after the pregnancy was concluded (the control group; n = 540). Periodontal disease was defined as presence of periodontal pockets of 4 mm or greater in depth at 12 or more probing sites in fully erupted teeth (typically excluding wisdom teeth). Treatments were conducted either by the hygienists or periodontists and included nonsurgical debridement of the subgingival and supragingival plaque, removal of local predisposing factors such as calculus, root planing, and adjustment of overhanging restorations. Comprehensive oral hygiene instructions and motivation were provided at each visit at a minimum of three weekly visits, with further visits if required. OUTCOME MEASURE: The primary outcomes were preterm birth or other major complications of pregnancy. RESULTS: There were no differences between the control and treatment groups in terms of: preterm birth [9.3% compared with 9.7%; odds ratio (OR), 1.05; 95% confidence interval (CI), 0.7-1.58; P 0.81); birthweight (3450 g versus 3410 g; P 0.12); pre-eclampsia (4.1% versus 3.4%; OR, 0.82; 95% CI, 0.44-1.56; P 0.55); or other obstetric endpoints. There were four unexplained stillbirths in the control group and no pregnancy losses in the treated group (P 0.12). Measures of foetal and neonatal wellbeing were similar in the two groups, including abnormalities in foetal heart rate recordings (P 0.26), umbilical artery flow studies (P 0.96), and umbilical artery blood gas values (P 0.37). The periodontal treatment was highly successful in improving health of the gums (P<0.01). CONCLUSIONS: The evidence provided by the present study does not support the hypothesis that treatment of periodontal disease during pregnancy in this population prevents preterm birth, foetal growth restriction, or pre-eclampsia. Periodontal treatment was not hazardous to the women or their pregnancies. PMID- 20348895 TI - No association between ischemic heart disease and periodontitis in women. AB - DESIGN: A cross-sectional study was conducted. SAMPLE: A random sample of women was used from the participants in a Prospective Population Study of women in Gothenburg that had been initiated in 1968. DATA SOURCES: Dental examinations were conducted by dentists and included panoramic radiography; a clinical inspection of the teeth, gums and oral mucosa; colour photography of the dentition, and a questionnaire. Myocardial infarction was diagnosed if at least two of the following criteria were present: 1) central chest pain >30 min; 2) transient rise of transaminase activities; and 3) typical electrocardiogram changes of recent onset. Angina pectoris was diagnosed using a questionnaire. The other independent variables were obtained from the medical part of the study and constituted other well-known risk factors for IHD. RESULTS: Among the dentate women in this study (N = 847), 74 had ischemic heart disease (IHD) and 773 did not. There was no statistically significant difference between numbers of pathological gingival pockets between these groups (58.1% had one or more pathological pockets in the IHD group versus 57.6% in the non-IHD group). Bivariate analysis of dentate individuals showed significant associations between IHD and number of missing teeth, age, body mass index, waist/ hip ratio, life satisfaction, hypertension, and levels of cholesterol and triglycerides. In the final multivariate logistic regression model, however, with the exception of age, only number of teeth [B17 teeth; odds ratio, 2.13; 95% confidence interval (CI), 1.20-3.77] was found to be significantly associated with IHD. Moreover, edentulous women had an odds ratio of 1.94 (95% CI, 1.05-3.60) in relation to IHD (age-adjusted model). CONCLUSIONS: In the present study, periodontitis did not seem to have a statistically significant relationship with IHD. The number of missing teeth showed a strong association with IHD, and this may act as a proxy variable tapping an array of different risk factors and behaviours. PMID- 20348896 TI - Patients undergoing craniofacial tumour ablation surgery may benefit from having the implants placed simultaneously instead of waiting. AB - DATA SOURCES: Medline, Embase and the Cochrane Library were searched for studies and the reference lists of the full-text articles were checked for any additional studies. STUDY SELECTION: Included studies were randomised clinical trials (RCT) and non-RCT, cohort studies, case-control studies, case reports, or reviews that addressed the placement of dental implants at the same time as primary oncological resection in people suffering from cancer of the head and neck (primary implant insertion); or addressed benign or malignant tumours and the placement of implants into the native maxilla, mandible and zygoma, and grafted tissue. Articles were restricted to those written in English. The title and abstracts were reviewed independently by two reviewers. DATA EXTRACTION AND SYNTHESIS: Data extraction was conducted independently and a qualitative synthesis of the data presented. RESULTS: Three case reports, 13 reviews, and 25 clinical studies were selected. Eight of the clinical studies referred solely to the insertion of dental implants at the time of primary oncological resection, and only two were of a prospective design. CONCLUSIONS: Published studies concerning primary dental implants were concisely summarised, so that the collected evidence base surrounding this approach to oral rehabilitation could inform head and neck cancer teams, particularly oncological surgeons, restorative dentists, and maxillofacial prosthodontists. PMID- 20348897 TI - Diagnostic delay broadly associated with more advanced stage oral cancer. AB - DATA SOURCES: Medline, Embase, ISI Proceedings and the reference lists of relevant articles were used to find relevant studies. STUDY SELECTION: Studies were included if: they presented original data from observational studies; included patients with a confirmed pathological diagnosis of oral or oropharyngeal squamous cell carcinoma; the outcome of interest was clearly defined as disease stage (TNM classification); the exposure of interest was total diagnostic delay, defined as the period between the patient noticing either the first sign or symptom and definitive diagnosis (data were collected from interviews using a standardised questionnaire and medical records); provided relative risks (RR) and 95% confidence intervals (CI) or provided enough data to allow calculation of these figures. DATA EXTRACTION AND SYNTHESIS: Quality assessment was undertaken independently by two reviewers and followed the recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). Meta-analysis was conducted using fixed and random-effects models. RESULTS: Nine studies carried out in nine different countries met the inclusion criteria and were included in the analysis. The fixed-effects pooled relative risk (RR) of advanced stages of oropharyngeal cancer when diagnostic delay is present was 1.32 (95% CI, 1.07-1.62). This association was stronger when the analysis was restricted to oral cancer (pooled RR, 1.47; 95% CI, 1.09-1.99) and when the delay was longer than 1 month (pooled RR, 1.69; 95% CI, 1.26-2.77). CONCLUSIONS: The probability for people with delayed diagnosis to present with an advanced-stage tumour at diagnosis was significantly higher than that of individuals with no delay in diagnosis. New prospective studies with strict methodology are needed, however, to shed more light on this association. PMID- 20348898 TI - Computer-aided design/ computer-aided manufacturing crown survival rates. AB - DESIGN: A randomised controlled trial (RCT) was conducted in a dental school. INTERVENTION: A total of 224 patients were randomised into two treatment groups, with 123 patients having teeth restored with KaVo Everest high-performance ceramic (HPC) crowns, fabricated by a computer-aided manufacturing procedure (KaVo Dental GmbH, Biberach an der Riss, Germany) and 101 patients receiving gold crowns. All crowns were conventionally cemented with glass-ionomer cement. OUTCOME MEASURE: Crowns were assessed for loss of vitality, surface roughness, fractures, marginal integrity, secondary caries at the crown margin, margin discolouration, marginal gap and crown loss at set time intervals of 6 and 12 months. The cumulative incidence of clinical complications was used as the criterion for failure. Time-to-event (failure) analysis was used for survival data. The incidence-free survival probabilities were then assessed using Kaplan Meier analysis. A proportional hazard model (Cox) was used to test the treatment effect. RESULTS: After an observation period of 6, 12 and 24 months, the prospective survival rates (Kaplan-Meier) for the KaVo Everest HPC crowns were 97.9%, 95.1% and 89.8%, and for the gold crowns were 100%, 94.8% and 92.7%, respectively. There were no significant differences between the two groups (P 0.2). The 1-year failure rates were 4.9% for the KaVo Everest HPC crowns and 5.2% for the gold crowns. The 1-year cumulative risks for loss of vitality, secondary caries, fractures, loss of crown and extraction of abutment of the analysed abutments (88) were 8.9%, 0%, 0%, 1.1% and 1.1%, respectively, for the gold crowns and 2.8%, 0%, 4.7%, 0% and 0.9%, respectively, for the ceramic crowns (107 analysed abutments). No perfect marginal fit was shown by 49.5% of the evaluated ceramic crowns and 26.1% of the gold crowns. CONCLUSIONS: The 12-month results indicate that Everest HPC crowns are suitable for posterior restorations, provided that an adequate tooth reduction is possible. The marginal fit shows potential for improvement. PMID- 20348899 TI - Critically appraising systematic reviews. AB - Critical appraisal is one of the key skills of evidence-based practice and is now increasingly being taught in dental schools. Here we outline the key principles of appraising systematic reviews. PMID- 20348901 TI - There's more than one way to skin a cat: response to "Reporting weight loss: is simple better?". PMID- 20348902 TI - Correction to: Self-reported stigmatization among candidates for bariatric surgery. PMID- 20348903 TI - Response to "The way we report weight loss". PMID- 20348905 TI - Double Holliday junctions are intermediates of DNA break repair. AB - Repair of DNA double-strand breaks (DSBs) by homologous recombination is crucial for cell proliferation and tumour suppression. However, despite its importance, the molecular intermediates of mitotic DSB repair remain undefined. The double Holliday junction (DHJ), presupposed to be the central intermediate for more than 25 years, has only been identified during meiotic recombination. Moreover, evidence has accumulated for alternative, DHJ-independent mechanisms, raising the possibility that DHJs are not formed during DSB repair in mitotically cycling cells. Here we identify intermediates of DSB repair by using a budding-yeast assay system designed to mimic physiological DSB repair. This system uses diploid cells and provides the possibility for allelic recombination either between sister chromatids or between homologues, as well as direct comparison with meiotic recombination at the same locus. In mitotically cycling cells, we detect inter-homologue joint molecule (JM) intermediates whose strand composition and size are identical to those of the canonical DHJ structures observed in meiosis. However, in contrast to meiosis, JMs between sister chromatids form in preference to those between homologues. Moreover, JMs seem to represent a minor pathway of DSB repair in mitotic cells, being detected at about tenfold lower levels (per DSB) than during meiotic recombination. Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs. PMID- 20348906 TI - Fructose 1,6-bisphosphate aldolase/phosphatase may be an ancestral gluconeogenic enzyme. AB - Most archaeal groups and deeply branching bacterial lineages harbour thermophilic organisms with a chemolithoautotrophic metabolism. They live at high temperatures in volcanic habitats at the expense of inorganic substances, often under anoxic conditions. These autotrophic organisms use diverse carbon dioxide fixation mechanisms generating acetyl-coenzyme A, from which gluconeogenesis must start. Here we show that virtually all archaeal groups as well as the deeply branching bacterial lineages contain a bifunctional fructose 1,6-bisphosphate (FBP) aldolase/phosphatase with both FBP aldolase and FBP phosphatase activity. This enzyme is missing in most other Bacteria and in Eukaryota, and is heat-stabile even in mesophilic marine Crenarchaeota. Its bifunctionality ensures that heat labile triosephosphates are quickly removed and trapped in stabile fructose 6 phosphate, rendering gluconeogenesis unidirectional. We propose that this highly conserved, heat-stabile and bifunctional FBP aldolase/phosphatase represents the pace-making ancestral gluconeogenic enzyme, and that in evolution gluconeogenesis preceded glycolysis. PMID- 20348907 TI - Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis. AB - Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis. PMID- 20348909 TI - Uni-directional liquid spreading on asymmetric nanostructured surfaces. AB - Controlling surface wettability and liquid spreading on patterned surfaces is of significant interest for a broad range of applications, including DNA microarrays, digital lab-on-a-chip, anti-fogging and fog-harvesting, inkjet printing and thin-film lubrication. Advancements in surface engineering, with the fabrication of various micro/nanoscale topographic features, and selective chemical patterning on surfaces, have enhanced surface wettability and enabled control of the liquid film thickness and final wetted shape. In addition, groove geometries and patterned surface chemistries have produced anisotropic wetting, where contact-angle variations in different directions resulted in elongated droplet shapes. In all of these studies, however, the wetting behaviour preserves left-right symmetry. Here, we demonstrate that we can harness the design of asymmetric nanostructured surfaces to achieve uni-directional liquid spreading, where the liquid propagates in a single preferred direction and pins in all others. Through experiments and modelling, we determined that the spreading characteristic is dependent on the degree of nanostructure asymmetry, the height to-spacing ratio of the nanostructures and the intrinsic contact angle. The theory, based on an energy argument, provides excellent agreement with experimental data. The insights gained from this work offer new opportunities to tailor advanced nanostructures to achieve active control of complex flow patterns and wetting on demand. PMID- 20348910 TI - Organic conductors: A dash of salt is superconducting. PMID- 20348908 TI - Perigord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis. AB - The Perigord black truffle (Tuber melanosporum Vittad.) and the Piedmont white truffle dominate today's truffle market. The hypogeous fruiting body of T. melanosporum is a gastronomic delicacy produced by an ectomycorrhizal symbiont endemic to calcareous soils in southern Europe. The worldwide demand for this truffle has fuelled intense efforts at cultivation. Identification of processes that condition and trigger fruit body and symbiosis formation, ultimately leading to efficient crop production, will be facilitated by a thorough analysis of truffle genomic traits. In the ectomycorrhizal Laccaria bicolor, the expansion of gene families may have acted as a 'symbiosis toolbox'. This feature may however reflect evolution of this particular taxon and not a general trait shared by all ectomycorrhizal species. To get a better understanding of the biology and evolution of the ectomycorrhizal symbiosis, we report here the sequence of the haploid genome of T. melanosporum, which at approximately 125 megabases is the largest and most complex fungal genome sequenced so far. This expansion results from a proliferation of transposable elements accounting for approximately 58% of the genome. In contrast, this genome only contains approximately 7,500 protein coding genes with very rare multigene families. It lacks large sets of carbohydrate cleaving enzymes, but a few of them involved in degradation of plant cell walls are induced in symbiotic tissues. The latter feature and the upregulation of genes encoding for lipases and multicopper oxidases suggest that T. melanosporum degrades its host cell walls during colonization. Symbiosis induces an increased expression of carbohydrate and amino acid transporters in both L. bicolor and T. melanosporum, but the comparison of genomic traits in the two ectomycorrhizal fungi showed that genetic predispositions for symbiosis-'the symbiosis toolbox'-evolved along different ways in ascomycetes and basidiomycetes. PMID- 20348911 TI - 35 atoms that changed the nanoworld. PMID- 20348912 TI - An extended defect in graphene as a metallic wire. AB - Many proposed applications of graphene require the ability to tune its electronic structure at the nanoscale. Although charge transfer and field-effect doping can be applied to manipulate charge carrier concentrations, using them to achieve nanoscale control remains a challenge. An alternative approach is 'self-doping', in which extended defects are introduced into the graphene lattice. The controlled engineering of these defects represents a viable approach to creation and nanoscale control of one-dimensional charge distributions with widths of several atoms. However, the only experimentally realized extended defects so far have been the edges of graphene nanoribbons, which show dangling bonds that make them chemically unstable. Here, we report the realization of a one-dimensional topological defect in graphene, containing octagonal and pentagonal sp(2) hybridized carbon rings embedded in a perfect graphene sheet. By doping the surrounding graphene lattice, the defect acts as a quasi-one-dimensional metallic wire. Such wires may form building blocks for atomic-scale, all-carbon electronics. PMID- 20348913 TI - Self-powered nanowire devices. AB - The harvesting of mechanical energy from ambient sources could power electrical devices without the need for batteries. However, although the efficiency and durability of harvesting materials such as piezoelectric nanowires have steadily improved, the voltage and power produced by a single nanowire are insufficient for real devices. The integration of large numbers of nanowire energy harvesters into a single power source is therefore necessary, requiring alignment of the nanowires as well as synchronization of their charging and discharging processes. Here, we demonstrate the vertical and lateral integration of ZnO nanowires into arrays that are capable of producing sufficient power to operate real devices. A lateral integration of 700 rows of ZnO nanowires produces a peak voltage of 1.26 V at a low strain of 0.19%, which is potentially sufficient to recharge an AA battery. In a separate device, a vertical integration of three layers of ZnO nanowire arrays produces a peak power density of 2.7 mW cm(-3). We use the vertically integrated nanogenerator to power a nanowire pH sensor and a nanowire UV sensor, thus demonstrating a self-powered system composed entirely of nanowires. PMID- 20348914 TI - Superconductivity in just four pairs of (BETS)2GaCl4 molecules. AB - How small can a sample of superconducting material be and still display superconductivity? This question is relevant to our fundamental understanding of superconductivity, and also to applications in nanoscale electronics, because Joule heating of interconnecting wires is a major problem in nanoscale devices. It has been shown that ultrathin layers of metal can display superconductivity, but any limits on the size of superconducting systems remain a mystery. (BETS)2GaCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene, is an organic superconductor, and in bulk it has a superconducting transition temperature Tc of approximately 8 K and a two-dimensional layered structure that is reminiscent of the high-Tc cuprate superconductors. Here, we use scanning tunnelling spectroscopy to show that a single layer of (BETS)2GaCl4 molecules on an Ag(111) surface displays a superconducting gap that increases exponentially with the length of the molecular chain. Moreover, we show that a superconducting gap can still be detected for just four pairs of (BETS)2GaCl4 molecules. Real space spectroscopic images directly visualize the chains of BETS molecules as the origin of the superconductivity. PMID- 20348915 TI - Asymmetric rostro-caudal inhibition in the primary olfactory cortex. AB - The importance of intracortical inhibitory circuits in setting the feature selective spatial organization of primary sensory cortices remains controversial. To address this issue, we examined the strength of interneuron-to-pyramidal cell connections across the rat anterior piriform cortex (aPC) and found a pronounced gradient of increasing pyramidal cell inhibition along the aPC rostro-caudal axis. This functional heterogeneity could govern aPC spatial activation in response to varying odor identities and features. PMID- 20348916 TI - The amygdala encodes specific sensory features of an aversive reinforcer. AB - Studies of reconsolidation, in which retrieved memories are altered and restored, offer an approach for exploring the associative structure of fear memory. We found that exposure to the unconditioned stimulus initiates an unconditioned stimulus-specific reconsolidation of learned fear in rats that depended on the amygdala. Thus, specific features of the unconditioned stimulus appear to be encoded in the amygdala as part of fear memories stored there. PMID- 20348917 TI - Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. AB - We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction. PMID- 20348918 TI - Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses. AB - When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks. PMID- 20348919 TI - Lateral prefrontal cortex and self-control in intertemporal choice. AB - Disruption of function of left, but not right, lateral prefrontal cortex (LPFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) increased choices of immediate rewards over larger delayed rewards. rTMS did not change choices involving only delayed rewards or valuation judgments of immediate and delayed rewards, providing causal evidence for a neural lateral-prefrontal cortex based self-control mechanism in intertemporal choice. PMID- 20348920 TI - p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain. AB - Axonal degeneration is important during development but has not been thought to function in the intact mature nervous system. Here, we provide evidence that degeneration of adult axons occurs in the intact rodent brain through a p75 neurotrophin receptor (p75NTR)- and myelin-dependent mechanism. Specifically, we show that p75NTR-mediated axonal degeneration prevents septal cholinergic axons from aberrantly growing onto myelinated tracts in vivo or on a myelin substrate in culture. Myelin also triggers local degeneration of p75NTR-expressing sympathetic axons that is rescued by increasing TrkA signaling or elevating intracellular cyclic AMP. Myelin-mediated degeneration occurs when neurotrophins bind to p75NTR, and involves p75NTR-dependent sequestration of Rho guanine nucleotide dissociation inhibitor (Rho-GDI). Moreover, degeneration, but not growth inhibition, requires downstream activation of Rho and caspase-6. These data indicate that p75NTR maintains the specificity of neural connectivity by preventing inappropriate sprouting onto myelinated tracts and provide a physiological explanation for myelin inhibition after neural injury. PMID- 20348921 TI - Atomic mutagenesis reveals A2660 of 23S ribosomal RNA as key to EF-G GTPase activation. AB - Following ribosomal peptide bond formation, the reaction products, peptidyl-tRNA and deacylated tRNA, need to be translocated from the A- and P-sites to the P- and E-sites, respectively. This process is facilitated by the GTPase elongation factor G (EF-G). The mechanism describing how the ribosome activates GTP hydrolysis is poorly understood in molecular terms. By using an 'atomic mutagenesis' approach, which allows the manipulation of specific functional groups on 23S rRNA nucleotides in the context of the entire ribosome, we disclose the adenine exocyclic N6 amino group at A2660 of the sarcin-ricin loop as a key determinant for triggering GTP hydrolysis on EF-G. We show that the purine pi system-expanding characteristics of the exocyclic functional group at the C6 position of A2660 are essential. We propose that stacking interactions of A2660 with EF-G may act as a molecular trigger to induce repositioning of suspected functional amino acids in EF-G that in turn promote GTP hydrolysis. PMID- 20348922 TI - Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. AB - Brain inflammation is a major factor in epilepsy, but the impact of specific inflammatory mediators on neuronal excitability is incompletely understood. Using models of acute and chronic seizures in C57BL/6 mice, we discovered a proconvulsant pathway involving high-mobility group box-1 (HMGB1) release from neurons and glia and its interaction with Toll-like receptor 4 (TLR4), a key receptor of innate immunity. Antagonists of HMGB1 and TLR4 retard seizure precipitation and decrease acute and chronic seizure recurrence. TLR4-defective C3H/HeJ mice are resistant to kainate-induced seizures. The proconvulsant effects of HMGB1, like those of interleukin-1beta (IL-1beta), are partly mediated by ifenprodil-sensitive N-methyl-d-aspartate (NMDA) receptors. Increased expression of HMGB1 and TLR4 in human epileptogenic tissue, like that observed in the mouse model of chronic seizures, suggests a role for the HMGB1-TLR4 axis in human epilepsy. Thus, HMGB1-TLR4 signaling may contribute to generating and perpetuating seizures in humans and might be targeted to attain anticonvulsant effects in epilepsies that are currently resistant to drugs. PMID- 20348923 TI - A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response. AB - Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit. Here we show that p85alphaalpha interacts with X-box-binding protein-1 (XBP-1), a transcriptional mediator of the unfolded protein response (UPR), in an endoplasmic reticulum (ER) stress-dependent manner. Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. This is associated with a decreased activation of inositol-requiring protein-1alpha (IRE1alpha) and activating transcription factor 6alphaalpha (ATF6alpha). Mice with deletion of p85alpha in liver (L-Pik3r1(-/-)) show a similar attenuated UPR after tunicamycin administration, leading to an increased inflammatory response. Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance. PMID- 20348924 TI - Pomc-expressing progenitors give rise to antagonistic neuronal populations in hypothalamic feeding circuits. AB - Hypothalamic neuron circuits regulating energy balance are highly plastic and develop in response to nutrient and hormonal cues. To identify processes that might be susceptible to gestational influences in mice, we characterized the ontogeny of proopiomelanocortin (POMC) and neuropeptide Y (NPY) cell populations, which exert opposing influences on food intake and body weight. These analyses revealed that Pomc is broadly expressed in immature hypothalamic neurons and that half of embryonic Pomc-expressing precursors subsequently adopt a non-POMC fate in adult mice. Moreover, nearly one quarter of the mature NPY+ cell population shares a common progenitor with POMC+ cells. PMID- 20348925 TI - T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. AB - Interferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN beta was effective in reducing EAE symptoms induced by T helper type 1 (T(H)1) cells but exacerbated disease induced by T(H)17 cells. Effective treatment in T(H)1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In T(H)17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-beta treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-gamma. In the absence of IFN-gamma signaling, IFN-beta therapy was ineffective in EAE. In RRMS patients, IFN-beta nonresponders had higher IL 17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta. PMID- 20348927 TI - Does 'asymptomatic hyponatremia' exist? PMID- 20348926 TI - The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. AB - Despite the fact that X-box binding protein-1 (XBP-1) is one of the main regulators of the unfolded protein response (UPR), the modulators of XBP-1 are poorly understood. Here, we show that the regulatory subunits of phosphotidyl inositol 3-kinase (PI3K), p85alpha (encoded by Pik3r1) and p85beta (encoded by Pik3r2) form heterodimers that are disrupted by insulin treatment. This disruption of heterodimerization allows the resulting monomers of p85 to interact with, and increase the nuclear translocation of, the spliced form of XBP-1 (XBP 1s). The interaction between p85 and XBP-1s is lost in ob/ob mice, resulting in a severe defect in XBP-1s translocation to the nucleus and thus in the resolution of endoplasmic reticulum (ER) stress. These defects are ameliorated when p85alpha and p85beta are overexpressed in the liver of ob/ob mice. Our results define a previously unknown insulin receptor signaling pathway and provide new mechanistic insight into the development of ER stress during obesity. PMID- 20348928 TI - Dialysis: Results of RENAL--what is the optimal CRRT target dose? PMID- 20348929 TI - Hypertension: Endothelin-receptor antagonists for treating hypertension. PMID- 20348930 TI - Diabetic nephropathy: Aldosterone breakthrough in patients on an ACEI. PMID- 20348931 TI - A case of lactic acidosis induced by linezolid. AB - BACKGROUND: A 36-year-old African American man with end-stage renal disease on chronic maintenance hemodialysis was transferred first from a hospital to a long term acute care facility for advanced care then to the intensive care unit of our university hospital with unexplained abdominal pain, nausea, hypotension, altered mental status and anion gap metabolic acidosis. Subsequent review of the patient's medication list revealed that the he had been on linezolid for 6 weeks for the treatment of vancomycin-resistant Enterococcus fecalis bacteremia. INVESTIGATIONS: Medical history, physical examination, laboratory tests, CT imaging of the thorax, abdomen and pelvis and PCR-based tests to determine the presence of polymorphisms in the 16S ribosomal RNA gene. DIAGNOSIS: Lactic acidosis associated with prolonged exposure to linezolid. MANAGEMENT: Discontinuation of linezolid. PMID- 20348934 TI - Science on the go. AB - Mobile devices are emerging as a viable way to maximize time to read and search our ever-expanding body of scientific information. We encourage our readers to download and use our new nature.com app and to provide us with feedback. PMID- 20348932 TI - Bacteriophage resistance mechanisms. AB - Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems. PMID- 20348935 TI - Preventing dehydration during sleep. PMID- 20348933 TI - Medically important bacterial-fungal interactions. AB - Whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. The interactions between these taxonomically diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. Human disease can develop from an imbalance between commensal bacteria and fungi or from invasion of particular host niches by opportunistic bacterial and fungal pathogens. This Review describes the clinical and molecular characteristics of bacterial-fungal interactions that are relevant to human disease. PMID- 20348936 TI - Manipulating the brain with epigenetics. PMID- 20348937 TI - Mouse brains wired for empathy? PMID- 20348938 TI - Protecting endangered memories. PMID- 20348939 TI - Speedy rod signaling. PMID- 20348941 TI - Sperm banking for male reproductive preservation: a 6-year retrospective multi centre study in China. AB - Sperm banking can preserve male fertility effectively, but the current conditions of sperm cryopreservation in China have not been investigated. This retrospective investigation was based on data collected at multiple centres in China from January 2003 to December 2008. The collected data included urogenital history, indication for cryopreservation, semen parameters, use rate, type of assisted reproductive technique (ART) treatment and pregnancy outcome. The study population included 1 548 males who had banked their semen during the study period at one of the clinics indicated above. Approximately 1.9% (30/1 548) of the cryopreserved semen samples were collected from cancer patients; about 88.8% (1 374/1 548) of the patients had banked their semen for ART and 8.6% (134/1 548) had a male infertility disease (such as anejaculation, severe oligozoospermia and obstructive azoospermia). The total use rate of cryopreserved semen was 22.7% (352/1 548), with 119 live births. The cancer group use rate was 6.7% (2/30), with one live birth by intracytoplasmic single sperm injection (ICSI). The ART group use rate was 23.2% (319/1 374), with 106 live births. The reproductive disease group use rate was 23.1% (31/134), with 12 live births. The semen parameters in each category varied; the cancer patient and infertility disease groups had poor semen quality. In vitro fertilization (IVF) and ICSI were the most common ART treatments for cryopreserved sperm. Semen cryopreservation as a salvage method is effective, but in many conditions it is underutilized, especially in cancer patients. Lack of awareness, urgency of cancer treatment and financial constraints are the main causes of the low access rate. The concept of fertility preservation should be popularized to make better use of this medical service in China. PMID- 20348940 TI - Gene-environment interaction and male reproductive function. AB - As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring. PMID- 20348942 TI - Eurycoma longifolia Jack in managing idiopathic male infertility. AB - This study investigated the effect of treatment with the proprietary standardized, water-soluble extract of the root of the Malaysian plant, Eurycoma longifolia Jack, which is thought to enhance male fertility with regard to higher semen volumes, sperm concentrations, the percentage of normal sperm morphology and sperm motility in male partners of sub-fertile couples with idiopathic infertility. A total of 350 patients were given 200 mg of the extract daily and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses in these patients showed significant improvement in all semen parameters. The proprietary extract of Eurycoma longifolia Jack significantly improved the sperm quality in these patients, allowing for 11 (14.7%) spontaneous pregnancies. PMID- 20348943 TI - Vascular gene transfer and drug delivery in vitro using low-frequency ultrasound and microbubbles. AB - AIM: To determine the effects of ultrasound exposure in combination with a microbubble contrast agent (SonoVue) on the cellular uptake and delivery of drugs/genes into human umbilical vein endothelial cells (HUVECs) as well as their biological effects on migration. METHODS: HUVECs in suspension were exposed to pulsed ultrasound with a 10% duty cycle in combination with various concentrations of a microbubble contrast agent (SonoVue) using a digital sonifier at a frequency of 20 kHz and an intensity of 3.77 W/cm(2) on the surface of a horn tip. Cell culture inserts were used to determine the cell migration ability. RESULTS: Exposure to pulsed ultrasound resulted in enhanced green fluorescent protein (EGFP) gene transfection efficiencies ranging from 0.2% to 2%. The transfection efficiency of HUVECs was approximately 3-fold higher in the presence of SonoVue than in its absence at the effective exposure time of 6 s. For drug delivery to HUVECs using ultrasound, the delivery efficiencies of a low-molecular weight model drug (TO-PRO-1, M(W) 645.38) were significantly higher when compared to drug delivery without ultrasound, with a maximum efficiency of approximately 34%. However, the delivery efficiencies of a high-molecular-weight model drug (Dextran-Rhodamine B, M(W) 70,000) were low, with a maximum delivery efficiency of nearly 0.5%, and gene transfection results were similarly poor. The migration ability of HUVECs exposed to ultrasound was also lower than that of the control (no exposure). CONCLUSION: The use of low-frequency and low-energy ultrasound in combination with microbubbles could be a potent physical method of increasing drug/gene delivery efficiency. This technique is a promising nonviral approach that can be used in cardiovascular disease therapy. PMID- 20348944 TI - A novel polymer-lipid hybrid nanoparticle for efficient nonviral gene delivery. AB - AIM: To develop a novel non-viral vector with high transfection efficiency and low cytotoxicity. METHODS: Poly (ethylene glycol) distearoylphosphatidylethanolamine (PEG-DSPE) was incorporated into polymer-lipid hybrid nanoparticles (PLN) to construct a PEG-DSPE modified long circulating PLN (L-PLN). The L-PLN was prepared by the emulsifying-solvent evaporation method, L PLN and L-PLN/DNA complexes were characterized. Both HEK293 and MDA-MB-231 cells transfected by L-PLN/DNA complexes were observed under a fluorescence microscope. The transfection efficiency of the complexes to HEK293 cells was further evaluated by flow cytometry. RESULTS: The GFP fluorescence intensity in HEK293 cells transfected by the L-PLN/DNA complexes (N/P=10) was about 37.2%, which was higher than those transfected by PLN alone or commercial Lipofectamine 2000. The L-PLN exhibited minimal toxicity at a low N/P ratio compared with other vectors. CONCLUSION: L-PLN as a novel gene delivery system, has higher transfection efficiency and acceptable cytotoxicity compared to the corresponding PLN, which is beneficial for the development of non-viral gene transfer vectors and may offer an alternative strategy for the future gene therapy. PMID- 20348945 TI - Stimulation of the adenosine A3 receptor reverses vascular hyporeactivity after hemorrhagic shock in rats. AB - AIM: To investigate whether adenosine A(3) receptors (A(3)AR) stimulation restore vascular reactivity after hemorrhagic shock through a ryanodine receptor (RyR) mediated and large conductance calcium-activated potassium (BK(Ca)) channel dependent pathway. METHODS: Rat hemorrhagic shock model (40 mmHg) and vascular smooth muscle cell (VSMC) hypoxic model were used. The expression of A(3)AR was determined by Western blot and RT-PCR. The effect of A(3)AR stimulation on RyR mediated Ca(2+) release in VSMCs was analyzed by the Fura-3/AM loading Ca(2+) imaging. The modulation of vascular reactivity to norepinephrine (NE) by A(3)AR stimulation was monitored by an isolated organ tension instrument. RESULTS: Decrease of A(3)AR expression is consistent with the loss of vasoreactivity to NE in hemorrhagic shock rats. The stimulation of A(3)AR with a selective agonist, IB MECA, could partly but significantly restore the vasoreactivity in the rats, and this restorative effect could be counteracted by MRS1523, a selective A(3)AR antagonist. In hypoxic VSMCs, RyR activation by caffeine significantly evoked the rise of [Ca(2+)] compared with the control cells, a phenomenon closely associated with the development of vascular hyporeactivity in hemorrhagic shock rats. The stimulation of A(3)AR with IB-MECA significantly blocked this over activation of RyR-mediated Ca(2+) release. RyR activation by caffeine and BK(Ca) channel activation by NS1619 attenuated the restoration of vasoreactivity to NE resulting from A(3)AR stimulation by IB-MECA after hemorrhagic shock; this attenuation effect could be antagonized by a selective BK(Ca) channel blocker. CONCLUSION: These findings suggest that A(3)AR is involved in the modulation of vasoreactivity after hemorrhagic shock and that stimulation of A(3)AR can restore the decreased vasoreactivity to NE through a RyR-mediated, BK(Ca) channel dependent signal pathway. PMID- 20348946 TI - Casein kinase 1 functions as both penultimate and ultimate kinase in regulating Cdc25A destruction. AB - The Cdc25A protein phosphatase drives cell-cycle transitions by activating cyclin dependent protein kinases. Failure to regulate Cdc25A leads to deregulated cell cycle progression, bypass of cell-cycle checkpoints and genome instability. Ubiquitin-mediated proteolysis has an important role in balancing Cdc25A levels. Cdc25A contains a DS(82)G motif whose phosphorylation is targeted by beta-TrCP E3 ligase during interphase. Targeting beta-TrCP to Cdc25A requires phosphorylation of serines 79 (S79) and 82 (S82). Here, we report that casein kinase 1 alpha (CK1alpha) phosphorylates Cdc25A on both S79 and S82 in a hierarchical manner requiring prior phosphorylation of S76 by Chk1 or GSK-3beta. This facilitates beta-TrCP binding and ubiquitin-mediated proteolysis of Cdc25A throughout interphase and after exposure to genotoxic stress. The priming of Cdc25A by at least three kinases (Chk1, GSK-3beta, CK1alpha), some of which also require priming, ensures diverse extra- and intracellular signals interface with Cdc25A to precisely control cell division. PMID- 20348947 TI - The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. AB - Overexpression of cyclooxygenase-2 (COX-2) and elevated levels of its enzymatic product prostaglandin E2 (PGE(2)) occur in the majority of colorectal cancers and have important roles in colorectal tumorigenesis. However, despite the established prosurvival role of PGE(2) in cancer, the underlying mechanisms are not fully understood. Here, we have shown that PGE(2) suppresses apoptosis via repression of the proapoptotic BH3-only protein Bim in human colorectal adenoma cells. Repression of Bim expression was dependent upon PGE(2)-mediated activation of the Raf-MEK-ERK1/2 pathway, which promoted Bim phosphorylation and proteasomal degradation. Reduction of Bim expression using RNA interference reduced spontaneous apoptosis in adenoma cells and abrogated PGE(2)-dependent apoptosis suppression. Treatment of COX-2-expressing colorectal carcinoma cells with COX-2 selective NSAIDs-induced Bim expression, suggesting that Bim repression via PGE(2) signalling may be opposed by COX-2 inhibition. Examination of Bim expression in two established in vitro models of the adenoma-carcinoma sequence revealed that downregulation of Bim expression was associated with tumour progression towards an anchorage-independent phenotype. Finally, immunohistochemical analyses revealed that Bim expression is markedly reduced in approximately 40% of human colorectal carcinomas in vivo. These observations highlight the COX-2/PGE(2) pathway as an important negative regulator of Bim expression in colorectal tumours and suggest that Bim repression may be an important step during colorectal cancer tumorigenesis. PMID- 20348948 TI - T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells. AB - T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14(ARF) and p21(WAF1/cip1). In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue. PMID- 20348949 TI - Membrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cells. AB - Mucins (MUC) are high molecular weight O-linked glycoproteins whose primary functions are to hydrate, protect, and lubricate the epithelial luminal surfaces of the ducts within the human body. The MUC family is comprised of large secreted gel forming and transmembrane (TM) mucins. MUC1, MUC4, and MUC16 are the well characterized TM mucins and have been shown to be aberrantly overexpressed in various malignancies including cystic fibrosis, asthma, and cancer. Recent studies have uncovered the unique roles of these mucins in the pathogenesis of cancer. These mucins possess specific domains that can make complex associations with various signaling pathways, impacting cell survival through alterations of cell growth, proliferation, death, and autophagy. The cytoplasmic domain of MUC1 serves as a scaffold for interaction with various signaling proteins. On the other hand, MUC4 mediates its effect by stabilizing and enhancing the activity of growth factor receptor ErbB2. MUC16, previously known as CA125, is a well-known serum marker for the diagnosis of ovarian cancer and has a key role in stimulation and dissemination of ovarian cancer cells by interacting with mesothelin and galectin. Therefore, herein we discuss the function and divergent mechanisms of MUC1, MUC4, and MUC16 in carcinogenesis in the context of alteration in cell growth and survival. PMID- 20348950 TI - Endoplasmic reticulum stress mediates radiation-induced autophagy by perk eIF2alpha in caspase-3/7-deficient cells. AB - As apoptosis defects limit efficacy of anticancer agents, autophagy has been proposed as a novel strategy for radiotherapy enhancement. We previously showed that caspase-3/7 inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the mechanism by which radiation triggers autophagy in caspase-3/7-deficient cells, and found the involvement of endoplasmic reticulum (ER) stress. The ER activates a survival pathway, the unfolded protein response, which involves ER-localized transmembrane proteins such as protein kinase-like ER kinase (PERK), inositol-requiring enzyme 1 and activating transcription factor-6. In this study, we found that PERK is essential for radiation-induced autophagy and radiosensitivity in caspase-3/7 double-knockout cells. Irradiation of these cells increased expression of phosphorylated-eIF2alpha. Similar results were seen after administration of tunicamycin (TM), a well-known ER stressor. Importantly, we found that the administration of TM with radiation in MCF-7 breast cancer cells, which are lacking functional caspase-3 and relatively resistant to many anticancer agents, enhances radiation sensitivity. Our findings reveal ER stress as a novel potential mechanism of radiation-induced autophagy in caspase-3/7-deficient cells and as a potential strategy to maximize efficiency of radiation therapy in breast cancer. PMID- 20348951 TI - PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. AB - Activation of cGMP-dependent protein kinase (PKG) has anti-tumor effects in colon cancer cells but the mechanisms are not fully understood. This study has examined the regulation of beta-catenin/TCF signaling, as this pathway has been highlighted as central to the anti-tumor effects of PKG. We show that PKG activation in SW620 cells results in reduced beta-catenin expression and a dramatic inhibition of TCF-dependent transcription. PKG did not affect protein stability, nor did it increase phosphorylation of the amino-terminal Ser33/37/Thr41 residues that are known to target beta-catenin for degradation. However, we found that PKG potently inhibited transcription from a luciferase reporter driven by the human CTNNB1 promoter, and this corresponded to reduced beta-catenin mRNA levels. Although PKG was able to inhibit transcription from both the CTNNB1 and TCF reporters, the effect on protein levels was less consistent. Ectopic PKG had a marginal effect on beta-catenin protein levels in SW480 and HCT116 but was able to inhibit TCF-reporter activity by over 80%. Investigation of alternative mechanisms revealed that cJun-N-terminal kinase (JNK) activation was required for the PKG-dependent regulation of TCF activity. PKG activation caused beta-catenin to bind to FOXO4 in colon cancer cells, and this required JNK. Activation of PKG was also found to increase the nuclear content of FOXO4 and increase the expression of the FOXO target genes MnSOD and catalase. FOXO4 activation was required for the inhibition of TCF activity as FOXO4-specific short-interfering RNA completely blocked the inhibitory effect of PKG. These data illustrate a dual-inhibitory effect of PKG on TCF activity in colon cancer cells that involves reduced expression of beta-catenin at the transcriptional level, and also beta-catenin sequestration by FOXO4 activation. PMID- 20348952 TI - EWS/ETS proteins promote expression and regulate function of the homeodomain transcription factor BRN3A. AB - Ewing's sarcoma family tumors (ESFTs or EFTs) express neuronal markers, which indicates they may originate from cells at least partly committed to neuronal lineage. However, recent publications suggest EFT originates in mesenchymal stem cells, and EWS/ETS fusion proteins characteristic of EFT activate neuronal marker expression to confer a neural phenotype on EFT. Here we show that the neuronal marker BRN3A/POU4F1 is expressed abundantly at the protein level in primary EFT but not in rhabdomyosarcoma and neuroblastoma, and EFT cells exhibit high activity of the BRN3A proximal autoregulatory region. EWS/FLI-1 siRNA reduces BRN3A expression and promoter activity and EWS/ETS proteins are bound to the BRN3A locus, suggesting a direct function for EWS/ETS proteins in control of BRN3A expression. Differentiation-associated and autoregulatory activities of BRN3A are respectively impaired and altered in EFT cells, and EWS/FLI-1 siRNA can restore some BRN3A function. A potentially novel function for BRN3A in EFT cells is identified. These results extend the hypothesis that EWS/ETS proteins induce expression of neuronal markers such as BRN3A in EFT by showing that the function of those same markers may be restricted or controlled in an EWS/ETS-dependent manner. PMID- 20348953 TI - Transcription factor regulatory networks in mammary epithelial development and tumorigenesis. AB - The mouse mammary gland is composed of three epithelial cell types, which include ductal, alveolar and myoepithelial cells. A hierarchy in which the mammary stem cell compartment gives rise to progressively restricted progenitors that ultimately form the luminal (ductal and alveolar) and myoepithelial lineages is now emerging. Although very little is known about the mechanisms controlling the differentiation of the myoepithelial cell lineage, a growing body of work reveals that the luminal cell fate is specified by a network of transcription factors. The precise roles of specific transcription factors in promoting differentiation of luminal progenitors into ductal or alveolar cells are now being elucidated. This review will discuss the importance of these recent observations and place them within the context of other transcription factor networks involved in mammary gland development and tumorigenesis. PMID- 20348954 TI - RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. AB - The study of RUNX3 in tumor pathogenesis is a rapidly expanding area of cancer research. Functional inactivation of RUNX3-through mutation, epigenetic silencing, or cytoplasmic mislocalization-is frequently observed in solid tumors of diverse origins. This alone indicates that RUNX3 inactivation is a major risk factor in tumorigenesis and that it occurs early during progression to malignancy. Conversely, RUNX3 has also been described to have an oncogenic function in a subset of tumors. Although the mechanism of how RUNX3 switches from tumor suppressive to oncogenic activity is unclear, this is of clinical relevance with implications for cancer detection and prognosis. Recent developments have significantly contributed to our understanding of the pleiotropic tumor suppressive properties of RUNX3 that regulate major signaling pathways. This review summarizes the important findings that link RUNX3 to tumor suppression. PMID- 20348955 TI - SSBP2 is an in vivo tumor suppressor and regulator of LDB1 stability. AB - SSBP proteins bind and stabilize transcriptional cofactor LIM domain-binding protein1 (LDB1) from proteosomal degradation to promote tissue-specific transcription through an evolutionarily conserved pathway. The human SSBP2 gene was isolated as a candidate tumor suppressor from a critical region of loss in chromosome 5q14.1. By gene targeting, we show increased predisposition to B-cell lymphomas and carcinomas in Ssbp2(-/-) mice. Remarkably, loss of Ssbp2 causes increased LDB1 turnover in the thymus, a pathway exploited in Trp53(-/-)Ssbp2(-/ ) mice to develop highly aggressive, immature thymic lymphomas. Using T-cell differentiation as a model, we report a stage-specific upregulation of Ssbp2 expression, which in turn regulates LDB1 turnover under physiological conditions. Furthermore, transcript levels of pTalpha, a target of LDB1-containing complex, and a critical regulator T-cell differentiation are reduced in Ssbp2(-/-) immature thymocytes. Our findings suggest that disruption of the SSBP2-regulated pathways may be an infrequent but critical step in malignant transformation of multiple tissues. PMID- 20348956 TI - A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. AB - Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. PMID- 20348957 TI - From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Using unbiased transcript profiling in an ALS mouse model, we identified a role for the co-stimulatory pathway, a key regulator of immune responses. Furthermore, we observed that this pathway is upregulated in the blood of 56% of human patients with ALS. A therapy using a monoclonal antibody to CD40L was developed that slows weight loss, delays paralysis and extends survival in an ALS mouse model. This work demonstrates that unbiased transcript profiling can identify cellular pathways responsive to therapeutic intervention in a preclinical model of human disease. PMID- 20348958 TI - The flowering gene SINGLE FLOWER TRUSS drives heterosis for yield in tomato. AB - Intercrossing different varieties of plants frequently produces hybrid offspring with superior vigor and increased yields, in a poorly understood phenomenon known as heterosis. One classical unproven model for heterosis is overdominance, which posits in its simplest form that improved vigor can result from a single heterozygous gene. Here we report that heterozygosity for tomato loss-of-function alleles of SINGLE FLOWER TRUSS (SFT), which is the genetic originator of the flowering hormone florigen, increases yield by up to 60%. Yield overdominance from SFT heterozygosity is robust, occurring in distinct genetic backgrounds and environments. We show that several traits integrate pleiotropically to drive heterosis in a multiplicative manner, and these effects derive from a suppression of growth termination mediated by SELF PRUNING (SP), an antagonist of SFT. Our findings provide the first example of a single overdominant gene for yield and suggest that single heterozygous mutations may improve productivity in other agricultural organisms. PMID- 20348959 TI - Keeping the tires warm. PMID- 20348960 TI - Genome-wide analysis of palindrome formation. PMID- 20348961 TI - Unlocking the pathogenesis of celiac disease. AB - A genome-wide association study reports more than a dozen new susceptibility loci for celiac disease. Analysis of eQTL data from these and previously established risk loci sheds light on the genetic pathways underlying this common autoimmune disease. PMID- 20348962 TI - Epigenetic marks identify functional elements. AB - Enhancers and transcription factor binding sites that control cell-specific transcription in higher eukaryotes can be found up to hundreds of kilobases from the promoters that they control, making their identification challenging. A new study uses a model based on histone modifications and chromatin dynamics to predict functional elements involved in androgen receptor response. PMID- 20348963 TI - Protective hemoglobinopathies and Plasmodium falciparum transmission. AB - Human hemoglobin variants are known to protect the host against severe malaria due to P. falciparum. A new study demonstrates that such genetic variation may also be associated with increased transmission of this pathogen from the human host to the Anopheles vector. PMID- 20348969 TI - Black hole in the lung. PMID- 20348970 TI - The EBMT activity survey 2008: impact of team size, team density and new trends. AB - Six hundred and fifteen centers from 45 countries reported a total 30,293 HSCT to this 2008 EBMT survey with 26,810 first transplants (40% allogeneic, 60% autologous). This corresponds to an increase of 7% for the allogeneic and 3% for the autologous HSCT. Main indications were leukemias (32%; 89% allogeneic); lymphomas (56%; 89% autologous); solid tumors (6%; 96% autologous); and non malignant disorders (6%; 88% allogeneic). There were more unrelated than HLA identical sibling donors (49 vs 46%). The proportion of peripheral blood transplants remained stable with 99% for autologous and 70% for allogeneic HSCT. One fifth of the teams with >80 HSCT performed more than half of all HSCT. This trend towards teams with higher numbers of HSCT was stronger for allogeneic (Gini coefficient 57%) than for autologous HSCT (Gini coefficient 38%). Transplant rates (number of transplants per 10 million inhabitants) increased in a close to linear way with increasing team density (number of transplant teams per 10 million inhabitants) and without saturation (R(2)=0.54); this connection was even stronger for allogeneic HSCT (R(2)=0.67). These data illustrate status and trends for HSCT in Europe. They provide a rational basis for planning and patient counseling. PMID- 20348971 TI - Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. AB - The efficacy and safety of CD52 antibody alemtuzumab to treat severe acute GVHD in 18 consecutive patients refractory to standard high-dose corticosteroid therapy is reported. Patients (age range 13-68 years) had developed acute GVHD grade III and IV with gut and/or liver involvement after stem cell transplantation from family donors (n= 7) or HLA-matched unrelated donors (n=11), including five donors with one or two HLA mismatches. Initially, in three patients, start doses of alemtuzumab in the range of 70-80 mg were applied and repeated after 3 to 4 weeks. Impressive responses were seen, but virus reactivation and bacterial infections were frequent. In an attempt to reduce this complication, the next nine patients received a reduced starting dose of 20-33 mg, and the last six patients received 3-13 mg repeated every 2-3 weeks. Seventeen of 18 patients responded to alemtuzumab, six patients are alive with a median follow-up of 108 weeks. Chronic GVHD was observed frequently. Although pronounced lymphocyte depletion requiring close monitoring for signs of infections seems inevitable for efficacy, alemtuzumab given in moderate doses has a substantial activity not only in intestinal but also in severe acute GVHD of the liver. PMID- 20348972 TI - An update to HLA nomenclature, 2010. AB - The WHO Nomenclature Committee for Factors of the HLA System met during the 15th International Histocompatibility and Immunogenetics Workshop in Buzios, Brazil in September 2008. This update is an extract of the main report that documents the additions and revisions to the nomenclature of human leukocyte antigen (HLA) specificities following the principles established in previous reports. PMID- 20348973 TI - Glutathione S-transferase T1-null seems to be associated with graft failure in hematopoietic SCT. AB - Hematopoietic SCT (HSCT) from HLA-matched donors is sometimes complicated by GVHD or graft rejection, because of mismatched mHA. This study presents data suggesting the involvement of glutathione S-transferase theta-1 (GSTT1), a phase II detoxifying enzyme encoded by GSTT1, in Ab-mediated rejection of HSCT in children with congenital hemoglobinopathies (CHs). Mismatch of GSTT1, which often features a deletion polymorphism variant, can have major consequences in solid organ transplantation outcome. In liver transplantation, it has been shown to lead to de novo hepatitis, whereas in kidney transplantation, chronic allograft rejection has been documented. In this study on 18 children with CH who underwent HSCT, five cases of graft rejection occurred, all in GSTT1-null patients, four of which featured anti-GSTT1 antibodies. The data suggest that when GSTT1-null patients are transplanted with a GSTT1-positive graft, rejection due to an Ab mediated immune response against GSTT1 displayed on transplanted stem cells may take place. Thus, it seems that detection of anti-GSTT1 antibodies in patients with a GSTT1-null genotype before transplantation may be predictive of graft rejection in the event of a GSTT1-positive donor. PMID- 20348974 TI - Knowledge and attitude of guardians towards eye health of primary school pupils in Ilorin, Nigeria. AB - OBJECTIVE: To determine guardians' knowledge and attitude towards pupils' eye health and draw implication for designing children-oriented ocular health messages. METHODS: A survey of 1,393 guardians selected through multistage random sampling in Ilorin, Nigeria. Using structured questionnaire, information sought included guardians' demographic characteristics, relationship to pupils, occupation, awareness of eye specialists, perception of normal vision, pupils' eye complaints, and ways of treating children eye conditions. Data analysis was done with SPSS 12.0.1. The test of significance was performed using Chi square test and significance was taken at p < 0.05. RESULTS: Guardians comprised 689 (49.4%) males and 704 (50.6%) females, mean age 43.61 SD 11.45. Most (88.54%) were pupils' parents and (11.46%) were relations (n=1,318); (55.15%) were in low paying occupations (n=1,311); (87.92%) were aware of eye specialists, (12.08%) unaware, (n=1192); (97.27%) adjudged normal vision at least important, (2.73%) not important (n=1,174). Pupils' eye complaints (n=914) included pain (26.04%), itching (24.73%), redness (21.12%), discharge (8.53%), blur vision (8.21%), photophobia (7.33%) and lacrimation (4.05%). Guardians (n=1,069) managed pupils' eye diseases using hospital treatment (61.65%), neglect (21.33%), self medication (9.26%) and traditional medication (7.76%). There were no significant associations between guardians' ways of managing pupils' eye diseases and their views on normal vision (p = 0.940); awareness of eye care specialists (p = 0.952); and economic occupational grouping (p = 0.959). CONCLUSION: The negative implications of neglecting eye diseases and use of self and harmful traditional eye-medications by some of the guardians need to be discouraged by appropriate eye health education. PMID- 20348975 TI - Facilities available for biomedical science research in the public universities in Lagos, Nigeria. AB - OBJECTIVES: Across the world, basic medical scientists and physician scientists work on common platforms in state-of-the-arts laboratories doing translational research that occasionally results in bedside application. Biotechnology industries capitalise on useful findings for colossal profit.1 In Nigeria and the rest of Africa, biomedical science has not thrived and the contribution of publications to global high impact journals is low.2 This work investigated facilities available for modern biomedical research in Lagos public universities to extract culprit factors. METHODS: The two public universities in Lagos, Nigeria were investigated by a cross sectional questionnaire survey of the technical staff manning biomedical science departments. They were asked about availability of 47 modern biomedical science research laboratory components such as cold room and microscopes and six research administration components such as director of research and grants administration. MAIN RESULTS: For convenient basic laboratory components such as autoclaves and balances, 50% responses indicated "well maintained and always functional" whereas for less convenient complex, high maintenance, state-of-the-arts equipment 19% responses indicated "well maintained and always functional." Respondents indicated that components of modern biomedical science research administration were 44% of expectation. CONCLUSIONS: The survey reveal a deficit in state-of the-arts research equipment and also a deficit in high maintenance, expensive equipment indicating that biomedical science in the investigated environment lacks the momentum of global trends and also lacks buoyant funding. In addition, administration supporting biomedical science is below expectation and may also account for the low contributions of research articles to global high impact journals. PMID- 20348976 TI - The use of drains in thyroid surgery. AB - OBJECTIVE: To evaluate the necessity and benefits of the use of drains and their limitations in thyroidectomy and assess their relationship with cost of surgery and hospital stay. METHODS: We conducted a prospective randomised study on 67 patients divided into two groups. A consisted of 35 patients with drain and B, 32 patients without drain between January 2005 and June 2007. All had subtotal thyroidectomy and the technique and method of closure were the same. No anticoagulant was used and the clotting profiles were within normal range in the two groups. RESULTS: The sixty seven patients recruited for the study were made up of 60 females (89.6%) and 7 males (10.4%). The mean age for group A was 50.14 +/- 10.7 years, group B was 51.97 +/- 9.5 years. The P value for the mean ages of the two groups is 0.464 (p=0.05,t=3.98).There was no blood transfusion. Three patients developed features of respiratory obstruction (respiratory distress and stridor) -the first 2, one from each group was as a result of laryngeal oedema from trauma of difficult intubation. The third was from group B, as a result of hemorrhage and haematoma collection (she was one of the controlled thyrotoxic patients). Two patients (5.7%) developed wound infections in group A, which increased morbidity, hospital bill and prolonged hospital stay as compared to group B. The highest volume of drainage of 35ml was from a woman with a big goiter (120g). Average drainage was 17.7 +/- 6.9ml. CONCLUSION: The use of drains is not necessary in all cases of thyroidectomy but for cases with large cavity post extraction and copious oozing in vascular glands. Some of the limitations to the use of drains are infections, this can prolong hospital stay and thereby increase hospital bill. PMID- 20348977 TI - Hypokalaemia in children hospitalised for diarrhoea and malnutrition in Calabar, Nigeria. AB - OBJECTIVE: To describe the acid base and electrolyte pattern of morbidity and mortality in children with diarrhoea and protein energy malnutrition. SETTING: The diarrhoea treatment and training unit of the university of Calabar teaching hospital was used for the study. DESIGN/METHODS: It was a prospective study in which consecutive children below the age of 15 years with protein energy malnutrition and diarrhoeal diseases admitted into the DTU were screened for acid base and serum electrolyte abnormalities. The study was carried out over a two year period from January 1997 to December 1998. RESULTS: Hypokalaemia was seen in 45 (23.4%) patients. This was second to acidosis. Metabolic acidosis was the commonest abnormality in this study and was seen in 108(56.3%) of the patients included in the study. There was hyponatraemia in 25(13%). Hypochloraemia in 8(4.2%) and hypernatraemia in 6(3.1%) of the patients respectively. CONCLUSION: This study has shown that hypokalaemia is a common electrolyte abnormality in children with severe protein energy malnutrition and diarrhoeal diseases. There is need to encourage the use of readily available interventions such as the UNICEF and WHO oral rehydration solution in patients with diarrhoea and/or severe protein energy malnutrition to reduce morbidity and mortality from acid base and electrolyte disturbances. PMID- 20348978 TI - Multicentre study of bone tumours. AB - BACKGROUND: Bone tumours are associated with high morbidity and mortality, especially in Lagos where late presentation, lack of diagnostic and therapeutic facilities as well as cultural and religious beliefs/practices constitute a formidable challenge to appropriate management. OBJECTIVE: To study the clinico pathologic pattern of primary bone tumours in Lagos. METHODS: A 2.5 decade retrospective review of cases of primary bone tumours at National Orthopaedic Hospital, Lagos (NOH), Lagos University Teaching Hospital (LUTH), and Havana Specialist Hospital (HSH) was done. Data such as age, gender, tumour type were extracted from the medical records and analysed. RESULTS: Six hundred and ninety eight (698) cases were reviewed. 364 cases were from NOH, 242 from LUTH and 92 from HSH. There were 10 cases in 1981, 13 in 1985, 19 in 1990, 30 in 1995, 38 in 2000 and 46 in 2005. The age range of cases was 6 to 85 years with a mean of 25.8 years and peak frequency in the 11-20 year age group. 423 patients (60.6%) were males and 275(39.4%) were females giving a male to female ratio of 1.5: 1. Three hundred and fifty-six (51.0%) were of benign while 342 (49.0%) were malignant. The commonest types were osteosarcoma 197 cases (28.2%), osteochondroma 106 cases (15.2%) and osteoclastoma 78 cases (11.2%) CONCLUSION: Primary bone tumours presenting to hospitals in Lagos are on the rise. They are common amongst males and teenagers. Majority are benign and comprise osteochondroma, osteosarcoma, osteoclastoma, aneurysmal bone cysts and chondrosarcoma. PMID- 20348979 TI - Clinico-pathologic patterns of extremity liposarcoma. AB - BACKGROUND: Liposarcoma is a tumour derived from primitive cells that undergo adipose differentiation. OBJECTIVE: To describe the clinico-pathological pattern of extremity liposarcoma in Lagos, Nigeria. METHODS: This is a descriptive study of patients with histologically established liposarcoma affecting the extremities seen at the Oncology unit of the National Orthopaedic Hospital, Lagos Nigeria. Demographic and clinical data ( including age, gender, presenting complaints anatomic location of lesions ), histologic type, clinical stage and treatment outcome were collected using a prepared proforma and analysed. RESULTS: Liposarcoma accounted for 6 [27.3%] of 22 cases of soft tissue sarcomas seen within the study period. All 6 were males with a M:F of 6:0. The age range was 36 59 years. Lesions were mostly located in the thigh 5/6 (83.3%). The most common histologic type was myxoid seen in 3/6 [50%]. All presented at stage T2bNoMo. Five (83.3%) had limb salvage surgery with adjuvant radiotherapy while one had ablative surgery. Survival and recurrent rates could not be determined as all patients were lost to follow-up soon after surgery. CONCLUSION: Liposarcoma is the commonest extremity soft tissue sarcoma seen in our centre, the myxoid type being the commonest histologic subtype. PMID- 20348980 TI - Birth preparedness and emergency readiness plans of antenatal clinic attendees in Ile-ife, Nigeria. AB - BACKGROUND AND OBJECTIVES: Adequate birth preparedness and emergency/complication readiness (BP/CR) planning could determine the survival of a pregnant woman and her unborn child in maternal emergency. The study assessed adequacy of BP/CR plans of antenatal clinic attendees in Ile-Ife, Osun State, Nigeria. METHODS: Pregnant women (less than 36 weeks gestation) attending antenatal clinics in selected health facilities were serially recruited into the study after they had given verbal informed consent. Data were collected with a purpose-designed questionnaire. SPSS version 11 statistical software was used for data entry and analysis. RESULTS: Four hundred pregnant women were recruited; 284 (71%) registered for antenatal care by 20 weeks of gestation. Concerning delivery planning, 350 (87.5%) had decided their place of delivery although 32 (9.1%) of these planned to deliver in mission houses or at home; 351 (87.8%) had started to purchase items needed for delivery or newborn care, 289 (71.0%) had identified someone to accompany them to health facility for delivery while 259 (64.8%) were saving money for delivery. Regarding emergency or complication readiness, knowledge of signs of severe maternal illness for which immediate care should be sought in an appropriate health facility was low, 113 (28.3%) respondents were able to mention 4 or more of such signs without prompting; 249 (62.3%) had made arrangements for transportation and 45 (11.3%) had identified potential blood donor. CONCLUSION: By the study criteria, 61% of the pregnant women studied made adequate preparations for delivery while 4.8% were ready for emergency/complication. It is recommended that greater emphasis be given to emergency/complication readiness during antenatal care sessions. PMID- 20348981 TI - Bladder cancer in Lagos: a 15 year histopathologic review. AB - OBJECTIVE: To present a 15 year retrospective pathologic study of bladder cancers. The aim is to document histologic pattern, prevalence, sex and age distribution of urinary bladder cancer. MATERIALS AND METHODS: The materials consisted of slides, paraffin embedded tissue blocks and histology request forms of all urinary bladder biopsies received at the Morbid Anatomy department of Lagos University Teaching Hospital Idi-Araba, Lagos from 1991 to 2005. Each sample represents a different patient. The study did not include information regarding the clinical or pathological stage of the tumours. RESULTS: Bladder malignancies comprised 39 (72.2 %) cases of all bladder biopsies and 0.86% of all diagnosed cancers in LUTH. The malignant lesions of the bladder showed a male preponderance with a M:F ratio of 4.6:1. The age range was 4-75 years with a mean age of 51.37 years and peak at 61-70 years age group. Transitional cell carcinoma was the commonest histological type accounting for 61.5% with a male to female ratio of 5:1 and mean age of 59 years. Squamous cell carcinoma accounted for 20.5% with a M:F ratio of 3:1 and showed a mean age of 47 years. Adenocarcinoma, anaplastic carcinoma and embryonal rhabdomyosarcoma accounted for 5.1%, 5.1% and 7.8% of cases respectively. CONCLUSION: Bladder cancer is not common in Lagos. The histopathologic pattern, prevalence, sex and age distribution of bladder cancer are similar to previous reports from schistosomiasis non endemic regions of Nigeria, Africa and the rest of the world. PMID- 20348982 TI - Macromastia: a review of presentation and management. AB - BACKGROUND: Macromastia is a condition of abnormal enlargement of the breast tissue in excess of the normal proportion. The condition may be caused by glandular hypertrophy, excessive fatty tissue or combination of both. The usual physiologic enlargement of female breast occurs over 3 to 5 years and the female breast size is related to body habitus and hereditary characteristics. METHOD: A review of the literatures of Macromastia was undertaken with emphasis on presentation and management. RESULT: The aetiology of macromastia is usually undetermined, however, hormonal excesses and hypersensitivity of the target organ have been found in some cases. Cases of hyperprolactinaemia has been reported by some workers. Immunological risk factors for development of macromastia have also been seen in some groups of patients with Myasthenia gravis, Chronic arthritis, and Hashimoto thyroiditis. Ultrasonography may show no breast parenchyma abnormalities, while mammography may be indicated in some patients who are 40 years or older. Hormonal assay can be done but its value in treatment is doubtful. Drugs are only marginally effective in reversing gigantomastia, therefore surgery remains the mainstay of treatment. CONCLUSION: Management of macromastia can be physically, socially and psychologically satisfying to both the patients and the surgeons. PMID- 20348983 TI - Review of skull base surgery in a Nigerian teaching hospital. AB - BACKGROUND AND OBJECTIVES: There is dearth of information on skull base surgery in Nigerians. This study was conducted to determine types of skull base lesions describe surgical approaches to the lesions and determine outcome of surgical management of the lesions over the study period. METHODS: We retrospectively reviewed the case notes of the patients who underwent skull base neurosurgical procedures between January 2001 and June 2007 in our centre. We obtained information on demography, clinical presentation, diagnosis, cranial computerised tomography findings, type of surgery, intraoperative findings and outcome of surgical management at the time of discharge from the hospital. RESULTS: Brain tumours were diagnosed in 28 patients, head injuries in 9 patients and one patient each had anterior encephalocele and frontal sinus mucocele. Eighteen patients had frontal craniotomy, three patients had temporal craniotomy and two patients had lateral rhinotomy in addition to bifrontal craniotomy. Two patients had frontoorbitotomy while retrosigmoid craniectomy was performed in one patient. Thirty three patients showed significant postoperative improvement at discharge. CONCLUSION: Brain tumour was the most common indication for skull base surgery in our centre. These tumours were mainly located in the anterior cranial fossa. Frontal craniotomy was the most common surgical approach. Non-availability of modern neurosurgical facilities confined us to the use of mainly traditional approaches. The availability of these facilities will assist in improving our management outcome in the future. PMID- 20348984 TI - Effectiveness of intra-operative Mitomycin-C in reducing the recurrence of pterygium in Irrua, Nigeria. AB - AIMS AND OBJECTIVES: To evaluate the effectiveness of intra-operative Mitomycin-C application after pterygium surgery in Irrua, Nigeria. MATERIALS AND METHODS: The medical records of all patients who had pterygium excision with intra-operative application of 0.4mg/ml Mitomycin C between June 2002 and May 2007 and followed up for at least a year were reviewed. RESULTS: Two hundred and forty three eyes (196 patients) had pterygium excision with intra-operative application of 0.4mg/ml Mitomycin C over this period. Male to female ratio was 2:1. The mean age of the patients was 47.1years (SD+ 15.4) Eleven eyes had recurrence after a minimum follow up period of one year. Six (54.5%) out of the eleven eyes that had recurrence had conjunctival granuloma and in such cases recurrence was early (between 2 to 3 months of surgery). Conjunctival granuloma was the main complication occurring in 35 eyes (14.4%). Occurrence of granuloma was significantly associated with recurrence (P =0.0006). Delayed wound healing occurred in 5 eyes (2.1%). There was no case of either scleral or corneal melting. CONCLUSION: Intra-operative application of 0.4mg/ml Mitomycin C is very effective in reduction of recurrence of pterygium after excision. Hence patients should be given the benefit of intra-operative use of Mitomycin C during pterygium surgery. PMID- 20348985 TI - Challenges in the organisation of a microsurgery laboratory in a low resource country. AB - OBJECTIVES: To highlight the problems encountered in the set up, organisation and operations of a microsurgery laboratory in a low resource tertiary care hospital in Lagos, Nigeria. METHODS: The basic infrastructural deficiencies of this setting were encountered. Significant administrative, logistic and technical obstacles needed to be overcome. The need for improvisation and flexibility in the organisation and operations of such a laboratory is highlighted. The use of locally available, cheaper variety of instruments and consumables in the microsurgery laboratories of developing countries with limited resources was demonstrated by our experience . CONCLUSION: We conclude that even in the setting of low resource tertiary centres found in many developing countries, challenges could be overcome and standard acceptable patency rates obtained in the microsurgery laboratory . PMID- 20348986 TI - Vesico-vaginal fistula in a patient with Meyer-Rokitansky-Kuster-Hauser syndrome. AB - This was a case of Gishiri cut in a patient with Meyer-Rokitansky-Kuster-Hauser syndrome resulting in a vesico-vaginal fistula and urethral loss. This followed an attempt to enlarge and lengthen the vagina to enhance penile penetration. Few cases of MRKH syndrome presenting with complications after an attempt at treatment by traditional birth attendants have been reported. This report is particularly of essence as most urinary fistulae in Nigeria are obstetric fistulae following prolonged obstructed labour. PMID- 20348987 TI - [The right to oneself]. PMID- 20348988 TI - [Should physicians prioritize according to costs or benefits?]. PMID- 20348989 TI - [Vaginal delivery in breech presentation]. PMID- 20348990 TI - [Close cooperation, but not oversteering]. PMID- 20348991 TI - [Pandemic preparedness seen from the district medical officer's office]. PMID- 20348992 TI - [Overdramatized pandemic]. PMID- 20348993 TI - [Misleading about leaders appointments at the Oslo University Hospital]. PMID- 20348994 TI - [Leadership and academic competence]. PMID- 20348995 TI - [Omega-3 and mortality]. PMID- 20348996 TI - [Proton pump inhibitors do not cause stomach cancer]. PMID- 20348998 TI - [Tendentious from Mysterud]. PMID- 20348999 TI - [Dangerous hospital medical records]. PMID- 20349000 TI - [Why do we still play the whisper game?]. PMID- 20349001 TI - [Few dental specialists in the districts]. PMID- 20349002 TI - [Brain drain from poor countries to rich countries]. PMID- 20349003 TI - [What do doctors think an MR examination costs?]. AB - BACKGROUND: By law, Norwegian physicians are required to evaluate costs and benefits of various medical interventions before patients are subjected to them. A prerequisite for filling this "gate-keeping" role adequately is to be informed about medical benefits and costs. This article examines physicians' knowledge of costs related to an MR (magnetic resonance) examination of a knee. MATERIAL AND METHODS: In 2006, the Research Institute of the Norwegian Medical Association sent a questionnaire to a representative sample of 1 400 Norwegian physicians. The following question was included: "What do you think is the total cost for a standard MR-examination of a knee (the sum of that paid by patients and the standard reclaimable fee [from health authorities] for this type of examination)". An unpaired t-test was used to compare answers from subgroups of doctors, and Pearson's correlation coefficient was used to establish relationships between cost estimates and other variables. RESULTS: Physicians' estimates for the costs of an MR examination showed great variation. 57 % of respondents over or underestimated the costs by 50 % or more than the actual price of 1250 NOK. The most common mistake was overestimation; 47 % estimated the cost to be above NOK 1875, while 10 % thought it was below NOK 625. INTERPRETATION: The results indicate that doctors should know more about costs, they cannot fulfil their role as gate-keepers without such knowledge. PMID- 20349004 TI - [New knowledge about Creutzfeldt-Jakob disease can yield therapeutic possibilities]. AB - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare neurological disease which is always terminal, often within months. The disease attracted attention in the 1990 s, when reports appeared about people acquiring the disease by eating meat from cattle infected with BSE (bovine spongiform encephalopathy). Recent progress within research on CJD has raised hopes about finding a treatment. The most promising results of this research are presented. MATERIAL AND METHODS: The review is based on articles (and references in them) identified through non systematic searches in PubMed. RESULTS: CJD is a disease that emerges when the cellular form of the prion protein PrPC is transformed into the disease associated PrPSc. Transgenic mice that did not express PrPC did not develop clinical signs of the disease after being exposed to prions. Both administration of antibodies towards PrPC and use of RNA interference technique to reduce PrPC gene expression increased the survival time in mice. Pentosan polysulphate (a drug against interstitial cystitis) infused intraventriculary in mice, prolonged the incubation time from 51 to 123 days. The drug has been tested in patients with CJD with promising results with respect to survival time. INTERPRETATION: New treatment modalities have shown results that raise hopes about finding curative treatment in the future. PMID- 20349005 TI - [Delivery of a breech presentation]. AB - BACKGROUND: Vaginal delivery in breech presentation is controversial, but in Norway vaginal delivery is recommended to certain groups of women. We have examined maternal and neonatal outcome at our hospital by mode of delivery to test whether our results support the recommendation. MATERIAL AND METHODS: We analyzed data from 385 women who delivered singleton breech fetuses after 34 weeks of gestation in the 10-year period 1997 - 2006 in Nordlandssykehuset, Bodo. Data were analyzed according to intended mode of delivery (caesarean section or vaginal delivery). Outcomes measured were neonatal and maternal mortality and morbidity, indication for caesarean section and use of forceps in vaginal delivery. RESULTS: 36 % of women delivered vaginally, and 39 % by planned and 25 % by acute caesarean section. Forceps were used in 16 % of vaginal deliveries. We found a higher incidence of early neonatal morbidity after vaginal delivery than after caesarean section (11/214 vs. 0/134, p < 0.008), but none of the children had any noticeable morbidity after one year. There was a higher risk of bleeding more than 1 000 ml after caesarean section (p = 0.01). INTERPRETATION: We found increased neonatal morbidity after vaginal deliveries of breech presentations, but the increase was about the same as that forming the basis for the national guidelines. We therefore choose to continue our practice with recommended vaginal delivery in breech presentation after careful selection. PMID- 20349006 TI - [Benzodiazepines to people with substance abuse problems?]. AB - Benzodiazepines are probably prescribed too often to people with substance abuse problems. The drugs often alleviate symptoms effectively on a short term, but pharmacodynamic interactions and development of dependence cause problems. Indistinct, but important side effects might be overlooked or misunderstood. Evidence-based practice should replace prescriptions based on unclear indications. PMID- 20349007 TI - [A man in his sixties with myocardial infarction, stent thrombosis and haemorrhage]. AB - A man in his sixties had acute ST-elevation myocardial infarction (treated with PCI [percutaneous coronary intervention] and antithrombotic medication) complicated by recurrent stent thrombosis. Excessive haematuria and discovery of a urinary bladder cancer complicated the antithrombotic treatment. Due to recurrent stent thrombosis the patient underwent a total of four PCIs and received the glycoprotein IIb/IIIa-inhibitor abciximab on two occasions. After the last administration of abciximab he developed excessive bleeding within an hour; a blood sample revealed severe thrombocytopenia (2 x 10(9)/l). Severe thrombocytopenia is a rare, but well-known complication to glycoprotein IIb/IIIa inhibitor treatment and is most often seen after readministration of abciximab. The problem of recurrent coronary stent thrombosis was solved by aorto-coronary bypass surgery, which should always be considered in patients with recurrent stent thrombosis and complications to anti-thrombotic treatment. When bleeding occurs in connection with abciximab treatment, especially within the first month after previous treatment, severe thrombocytopenia should always be considered as a possible cause. Abciximab should be avoided in patients with a history of severe abciximab-related thrombocytopenia. PMID- 20349008 TI - [Complications and complicated decisions]. PMID- 20349009 TI - [Anaesthesia for open-heart surgery in adults]. AB - BACKGROUND: Each year, about 5 000 adults undergo heart surgery (most of them open-heart surgery) in Norway. The purpose of this overview is to address specific problems associated with anaesthesia in these patients. MATERIAL AND METHODS: The paper is based on literature identified through a non-systematic search in PubMed and own experience with clinical work and research. RESULTS: In Norway, general anaesthesia is always used in open-heart surgery. Some patients have such severely impaired heart function that it needs to be supported by inotropic drugs or mechanical devices. The patients are given heparin during surgery, and many also receive preoperative treatment with drugs that affect haemostasis. Profuse bleeding, during or after surgery, is sometimes challenging. The brain is at risk because the blood flow generated by the heart-lung machine is unphysiological, and because air or solid particles may embolize from the heart or aorta during the intervention. Renal failure after heart surgery is a serous complication with high mortality. Some anaesthetics probably have direct cardioprotective effects. Tight control of blood glucose seems to be justified, even if the level of optimal serum blood glucose is still debated. INTERPRETATION: Several organ systems are at risk during heart surgery. In addition to providing pleasant and painless sleep for the patient and good working conditions for the surgeon, the anaesthetist cooperates with the team about securing optimal organ protection. PMID- 20349010 TI - [Non-cardiac surgery in patients with cardiac disease]. AB - BACKGROUND: Patients with cardiac disease have a higher incidence of cardiovascular events after non-cardiac surgery than those without such disease. This paper provides an overview of perioperative examinations and treatment. MATERIAL AND METHODS: Own experience and systematic literature search through work with European guidelines constitute the basis for recommendations given in this article. RESULTS: Beta-blockers should not be discontinued before surgery. High-risk patients may benefit from beta-blockers administered before major non cardiac surgery. Slow dose titration is recommended. Echocardiography should be performed before preoperative beta-blockade to exclude latent heart failure. Statins should be considered before elective surgery and coronary intervention (stenting or surgery) before high-risk surgery. Otherwise, interventions should be evaluated irrespective of planned non-cardiac surgery. Patients with unstable coronary syndrome should only undergo non-cardiac surgery on vital indications. Neuraxial techniques are optimal for postoperative pain relief and thus for postoperative mobilization. Thromboprophylaxis is important, but increases the risk of epidural haematoma and requires systematic follow-up with respect to diagnostics and treatment. INTERPRETATION: Little evidence supports the use of different anaesthetic methods in cardiac patients that undergo non-cardiac surgery than in other patients. Stable circulation, sufficient oxygenation, good pain relief, thromboprophylaxis, enteral nutrition and early mobilization are important factors for improving the perioperative course. Close cooperation between anaesthesiologist, surgeon and cardiologist improves logistics and treatment. PMID- 20349011 TI - [Modern pharmacological principles for intravenous anaesthesia]. AB - BACKGROUND: Anaesthetic pharmacology is characterized by use of drugs in high doses for a short period of time. Knowledge of pharmacokinetics is important for precise control of drug effects (onset, maintenance and offset). MATERIAL AND METHODS: The paper is based on own research, experience from clinical practice, teaching, and up-to-date knowledge of the available literature. RESULTS: Traditional pharmacokinetic terms; such as volume of distribution, clearance and elimination half-life are useful within anaesthesiology, but two other important concepts should be considered: time to effect onset (keO) and context sensitive elimination half-life. keO is dependent upon distribution of drug from plasma to site of effect and the speed of cellular effect activation. The context sensitive elimination half-life upon discontinuation of a drug depends on how long the drug has been administered, and is shorter than terminal elimination half-life for anaesthetic drugs when used shorter than 12 - 24 hrs. With short-term use of drugs there is a profound initial drug distribution into tissues in addition to elimination. With prolonged use there is more drug deposited in the tissues, lower diffusion gradient and prolonged context sensitive elimination half-time. Computerized infusion pumps (Target Control Infusion, TCI) enable dosing of opioids or propofol to a preset concentration, either in plasma or at the site of effect. INTERPRETATION: Knowledge of pharmacologic principles and modeling from studies on volunteers and patients form the basis for good clinical monitoring of anaesthetic drug effects. PMID- 20349012 TI - [Assessing the depth-of-hypnosis]. AB - BACKGROUND: There has been a breakthrough in the understanding of anaesthetic drug effects during the last two decades, and new monitors aimed at quantifying such effects have been developed. MATERIAL AND METHODS: This review is based on publications from the last 15 years, oral presentations, and rewritten parts of the author's PhD thesis. RESULTS: General anaesthesia can be regarded as a combination of hypnosis (sleep), analgesia and muscle relaxation. Modern anaesthetic drugs aim at each of these effects separately. Pharmacological variation makes it impossible to find one dose suitable for all, so tools for measuring drug effects in the individual patient are warranted. Monitors for measuring depth-of-hypnosis and partly analgesic effect are commercially available. Among these, BIS (bispectral index), based on EEG, is by far the best documented. BIS is proven useful for preventing undesired awareness and overdosing, but there are major limitations. Use of such technology in clinical practice is under constant debate. INTERPRETATION: Even though the BIS technology is promising and used widely, no health authorities have so far recommended that such monitors should be compulsory during general anaesthesia, but rather that it should be considered on an individual basis. So far, it seems like this is a sensible approach in Norway as well. PMID- 20349013 TI - [Obesity surgery in inflammatory bowel disease]. PMID- 20349014 TI - [Love, self-delusion and disease]. PMID- 20349015 TI - [Mistrust and manipulation in dr House]. PMID- 20349017 TI - [The fight against tuberculosis]. PMID- 20349018 TI - [Easter Island--early genetic traces after American Indians]. PMID- 20349020 TI - The pituitary endocrine mechanisms involved in mammalian maturation: maternal and photoperiodic influences. AB - This review is designed to describe some pituitary mechanisms indispensable for growth and sexual maturation during the neuroendocrine adaptation of the female mammal to the extrauterine environment. We define the phases of postnatal development on the basis of secretory patterns of hormones. The infantile period is characterized by accelerated growth, and elevated secretion of growth hormone (GH) and follicle-stimulating hormone (FSH) in contrast to the diminished secretion of luteinizing hormone (LH). The transition from infancy to prepuberty generates the attenuation of somatic growth in non-primate mammals and the beginning of sexual maturation. The mechanisms of this transition involve the effects of weaning, which is associated with a rupture of the young-mother bond and, if abrupt, results in the stress of maternal deprivation. Maternal deprivation involves the stress-like endocrine response of pituitary and influences the mechanisms underlying the secretion of GH and FSH. An acute decrease in the secretion of GH and FSH at the initiation of prepuberty and an increase in the storage and pulsatile release of LH according to progressive prepubertal stages are pituitary endocrine features of post-infantile maturation. There are two factors important for timing of puberty, the maturity of gonadotroph population manifested by the adequate size of LH-containing cell subpopulation and the circumstances of an external environment optimal for reproductive functions in adults. Thus, the intrapituitary endocrine mechanisms of maturation have a psychosomatic nature during weaning and histomorphological nature during the postinfantile transition to puberty. In seasonal breeders, the endocrine timing of puberty has a circumannual seasonal nature. PMID- 20349021 TI - Cryptorchidism and long-term consequences. AB - Cryptorchidism has been on the rise for several decades and can be observed with frequency of 1-2% of males within the first year of age. It may appear as an isolated disorder or can be a consequence of genetic and endocrine abnormalities connected with somatic anomalies. Its genetic background still seems to be unclear although a range of genes can be responsible for the development of this syndrome. Cryptorchidism can be associated with serum testosterone level although the often co-existing hypogonadotropic hypogonadism may also indicate the involvement of pituitary hormones. Recently, environmental factors have been blamed for cryptorchidism induction. Autoimmune reactions in conjunction with steroid hormones regulating immune response can be also partly responsible for cryptorchidism etiology. The appearance of antisperm antibodies can be considered as a marker or a serious side-effect of uncorrected cryptorchidism. If so, it could be implied that early surgery (orchidopexy) should be beneficial since it may prevent antisperm antibodies induction or at least eliminate them in the post operative period. PMID- 20349022 TI - Distribution of androgen and progesterone receptors in the spiny mouse (Acomys cahirinus) ovary during postnatal life. AB - This study describes the localization of androgen (AR) and progesterone (PR) receptors in the developing ovary in the spiny mouse. The immunohistochemical analysis showed for the first time the expression of AR and PR proteins in the ovary as early as in one day-old females. Both AR and PR were present in germinal epithelium cells, stromal cells as well as in the granulosa and theca layer of ovarian follicles. On days 7, 14, 21, 30, 60 and 90, the distribution of AR and PR depended on the stage of follicular development rather than on the animal's age. A novel observation was that PR protein was detected not only in granulosa cells of preovulatory follicles, but also in the growing and early antral follicles. It was demonstrated that there is a different pattern of AR and PR immunoexpression throughout folliculogenesis. In contrast to AR, whose expression decreased during follicular development, the PR immunostaining increased during this time. It is concluded that androgens and progesterone may play an important role in the early stage of follicular development in the spiny mouse. PMID- 20349023 TI - The distribution of corpora lutea and ovarian follicular development in pregnant goats. AB - The main objective of the study was to determine the number of growing follicles (diameter>or=4 mm) with regards to the distribution of corpora lutea (CL) on the ovaries in pregnant goats. Growing follicles with a diameter greater than 5 mm i.e. large follicles were also recorded and analyzed. Daily ultrasonography (USG) examinations of ovaries were made in six Polish White Goats starting from the day of estrus detection (December/January) until parturition (May/June). An individual profile of follicular growth during the entire pregnancy was recorded for every goat. Three goats with CL present only on one ovary were included into group CL/0, and the three other goats with CL on both ovaries were in CL/CL group. The mean numbers of growing (52.0+/-11.3) and large (21.0+/-7.1) follicles during the entire pregnancy in group CL/0 were significantly (p or = 20% indicating that no or weak relationships were identified for most individual pairs. Three traits (total tocopherol content in maize kernel, plant height and kernel length) and 1,414 SNPs with missing data < 20% were used to evaluate the performance of four models for association mapping analysis. For all traits, the model controlling relative kinship (K) performed better than the model controlling population structure (Q), and similarly to the model controlling both population structure and relative kinship (Q + K) in this panel. Our results suggest this maize panel can be used for association mapping analysis targeting multiple agronomic and quality traits with optimal association model. PMID- 20349035 TI - Analysis of TBC1D4 in patients with severe insulin resistance. PMID- 20349036 TI - Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle. AB - AIMS/HYPOTHESIS: We investigated the direct effect of a nitric oxide donor (spermine NONOate) on glucose transport in isolated human skeletal muscle and L6 skeletal muscle cells. We hypothesised that pharmacological treatment of human skeletal muscle with N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2 ethylenediamine (spermine NONOate) would increase intracellular cyclic GMP (cGMP) levels and promote glucose transport. METHODS: Skeletal muscle strips were prepared from vastus lateralis muscle biopsies obtained from seven healthy men. Muscle strips were incubated in the absence or presence of 5 mmol/l spermine NONOate or 120 nmol/l insulin. The L6 muscle cells were treated with spermine NONOate (20 micromol/l) and incubated in the absence or presence of insulin (120 nmol/l). The direct effect of spermine NONOate and insulin on glucose transport, cGMP levels and signal transduction was determined. RESULTS: In human skeletal muscle, spermine NONOate increased glucose transport 2.4-fold (p < 0.05), concomitant with increased cGMP levels (80-fold, p < 0.001). Phosphorylation of components of the canonical insulin signalling cascade was unaltered by spermine NONOate exposure, implicating an insulin-independent signalling mechanism. Consistent with this, spermine NONOate increased AMP-activated protein kinase (AMPK)-alpha1-associated activity (1.7-fold, p < 0.05). In L6 muscle cells, spermine NONOate increased glucose uptake (p < 0.01) and glycogen synthesis (p < 0.001), an effect that was in addition to that of insulin. Spermine NONOate also elicited a concomitant increase in AMPK and acetyl-CoA carboxylase phosphorylation. In the presence of the guanylate cyclase inhibitor LY-83583 (10 micromol/l), spermine NONOate had no effect on glycogen synthesis and AMPK-alpha1 phosphorylation. CONCLUSIONS/INTERPRETATION: Pharmacological treatment of skeletal muscle with spermine NONOate increases glucose transport via insulin independent signalling pathways involving increased intracellular cGMP levels and AMPK-alpha1-associated activity. PMID- 20349037 TI - Triaging for adult critical care in the event of overwhelming need. AB - INTRODUCTION: Predictions of the need for critical care within the H1N1 influenza pandemic suggested overwhelming need beyond potential resources, necessitating rationing of care via triaging. METHOD: The triage model described was derived from informed discourse within a conjoined NHS and University Clinical Ethics Committee, supplemented by specialists in intensive care and infectious diseases. THE MODEL: The triage methodology described is justified ethically primarily upon 'utilitarian' principles within an aggregate public health model, with additional reference to 'fairness'. Advantages of such a model, which partially suspends usual clinical judgment applied to individuals in favour of also utilizing organ failure scores, include minimization of aggregate influenza morbidity and mortality, and minimization of psychological stress upon staff making triaging decisions. Legally, in England and Wales, the model is uncontentious as regards rationing of admission to critical care; however, the law adopts 'futility' as the core justification for withdrawal of treatment, applied to the individual, thus failing to allow for rationing through triaging individuals out of critical care in the interest of other patients with better chances of survival. There is therefore a mismatch between a clinically and ethically acceptable model of triaging, based upon a public health approach, and the law, based upon the paradigm of the individual patient. CONCLUSION: The good fortune that the H1N1 pandemic was less severe than predicted, allowing time for calm consideration, debate and decision making about what model of triaging should be adopted whenever it might be necessary in the future. It is in the interest of the health of the nation, and government, to decide upon a critical care triaging model while there is not an imminent health service crisis. PMID- 20349038 TI - Olprinone attenuates the development of ischemia/reperfusion injury of the gut. AB - PURPOSE: Splanchnic artery occlusion (SAO) shock is a severe form of circulatory shock produced by ischemia and reperfusion of the splanchnic organs. The occlusion and reperfusion of the splanchnic arteries causes activation and adhesion of polymorphonuclear neutrophils (PMNs), release of proinflammatory substances and the formation of both species of oxygen and nitrogen derivatives free radicals. Olprinone is a specific phosphodiesterase-III inhibitor that has many properties; one of which is anti-inflammatory actions at therapeutic concentrations clinically used for heart failure. In this study, we wanted to evaluate the pharmacological action of olprinone (a PDEIII inhibitor) on SAO shock in mice. METHODS: SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Olprinone was given at a dose of 0.2 mg/kg i.p. 15 min before reperfusion. RESULTS: Our results indicated that olprinone up-regulated cAMP in injured ileum tissue, and decreased the ileum tissue damage after 1 h of reperfusion in SAO shock mice. Moreover, olprinone decreased NF-kappaB expression; the nitration of tyrosine residues; the phosphorylation of p38 MAPK and JNK; cytokine production (TNF-alpha and IL-1beta); ICAM-1 and P-selectin expression and apoptosis in the injured ileum. CONCLUSIONS: These results could imply a future use of olprinone in the therapy of ischemia and reperfusion shock. PMID- 20349039 TI - The effect of microRNA-21 on proliferation and matrix synthesis of chondrocytes embedded in atelocollagen gel. AB - The objective of this study was to investigate the effect of microRNA-21 (miR-21) on the proliferation and matrix synthesis of chondrocytes embedded in atelocollagen gel. Articular cartilage was harvested aseptically from the knee and hip joints of rats. In the experimental group, double-stranded miR-21 was transfected into the chondrocytes, and in the control group, scrambled siRNA was used. After that, chondrocytes were cultured in atelocollagen gel for 3 weeks. At 1, 2, and 3 weeks after transfection, the cell numbers were counted, and the expression levels of Col2a1 and aggrecan were measured by real-time PCR. Histological analysis by toluidine blue staining was performed at 3 weeks. The cell number in the experimental group rapidly increased compared to the control group. The expression levels of Col2a1 and aggrecan in the experimental group were higher than in the control. Histological analysis revealed that many more cells with a metachromatic stain were present in the experimental group than in the control. This study demonstrated that miR-21 promotes high proliferation and matrix synthesis of chondrocytes embedded in atelocollagen gel. PMID- 20349040 TI - Arthroscopic Bankart repair: results and risk factors of recurrence of instability. AB - The purpose of this study was to discover the recurrence rate of instability after arthroscopic Bankart repair and to assess risk factors for recurrence, with special interest in bone defects seen on preoperative plain radiographs. Consecutive unselected patients (182; 186 shoulders) with recurrent instability (redislocation or subluxation) after initial traumatic anteroinferior shoulder dislocation were operated on using arthroscopic suture-anchor repair at our institution during 2000-2005. Demographic data and details of the operation were retrospectively reviewed from case records, and glenoid and Hill-Sachs lesions were assessed from preoperative radiographs. The primary outcome measure was recurrence of instability (redislocation or subluxation). Functional results were assessed via Oxford instability scores and subjective shoulder values (SSVs), using postal questionnaires. One hundred and seventy-four shoulders (170 patients) were assessed after a median of 51 (range 24-95) months' follow-up. The recurrence rate of instability was 19% (redislocation 9% and subluxation 10%). Eighteen patients (10%) needed further surgery. The mean Oxford instability score was 21 and the mean SSV 84%. The recurrence rate among patients aged 20 or less was 44% and among patients over 20, 12%. Multivariate logistic regression analysis showed that age <=20 (OR 8.8), Hill-Sachs lesion (OR 3.3), glenoid erosion (OR 2.7) and length of follow-up (OR 1.5) were the most important risk factors for recurrence. Young age is the most important risk factor for recurrence of instability after arthroscopic suture-anchor Bankart repair. Bone defects seen in preoperative plain radiographs are less important and more accurate imaging is needed to reveal their true role for recurrence of instability. PMID- 20349041 TI - Opening-wedge high tibial osteotomy without bone graft. AB - Open wedge high tibial osteotomy has become the trend for correction of varus knee deformities. The drawbacks were the need of autogenous bone graft with its associated morbidity, and later the use of bone substitutes with their cost and delayed healing. In this study, a total of 58 consecutive patients underwent high tibial osteotomy with internal fixation by wedge (toothed) plate and screws without bone graft, from 2004 to 2008. Age of the patients ranged from 24 to 65 years. There were 37 women and 21 men. The osteotomy opening size ranged from 8 to 14 mm. The mean follow-up was 38 months. The osteotomy united in all patients. Average time to union was 12.4 weeks (range 8-16 weeks). Partial loss of correction occurred in one osteotomy. There was significant difference between the healing time and the size of the osteotomy opening. The results at the final follow-up using the HSS score were excellent in 51 knees (88%) and good in seven knees (12%). Despite the routine addition of bone graft as a part of the high tibial osteotomy procedure, this study supports medial opening-wedge high tibial osteotomy up to 14 mm without bone graft or bone substitutes, which shortens the operative time and avoids unnecessary morbidity. PMID- 20349042 TI - Standardized cartilage biopsies from the intercondylar notch for autologous chondrocyte implantation (ACI). AB - Autologous chondrocyte implantation (ACI) is an established therapy for the treatment of cartilage defects across the knee joint. Even though different techniques for initial biopsy have been described, the exact location, depth, and volume of the biopsy are chosen individually by the treating surgeon. This study evaluated 252 consecutive cartilage biopsies taken from the intercondylar notch with a standardized hollow cylinder system for the isolation and in vitro cultivation of human chondrocytes assigned to ACI. All biopsies were assessed for weight of total cartilage obtained, cartilage biopsy weight per cylinder, biopsy cylinder quality, and initial cell count after digestive cellular isolation as well as cell vitality. Parameters were correlated with individual patient parameters. Mean patient age was 35.1 years (median 35.9; range 14.7-56.4). Adequate amounts of cartilage assigned to chondrocyte in vitro cultivation could be harvested in all cases. The mean overall biopsy weight averaged 75.5 mg (SD +/ 44.9) and could be identified as main factor for initial cell number (mean 1.05E+05; SD +/- 7.44E+04). No correlation was found between the initial cell count and patient age (correlation coefficient r = 0.005) or grade of joint degeneration (r = 0.040). Concerning cell viability, a total of 4.4% (SD + 3.0) of the chondrocytes harvested were apoptotic. Cartilage biopsies from the intercondylar notch using a standardized hollow cylinder system provides a reliable, safe, and successful method to obtain articular cartilage for further in vitro cultivation of articular chondrocytes to achieve autologous chondrocyte transplantation. PMID- 20349043 TI - Structural parameters of normal and osteoporotic human trabecular bone are affected differently by microCT image resolution. AB - This study employed microCT to investigate whether image resolution affects bone structural parameters differently in healthy normal and osteoporotic trabecular bone. With increasing image voxel size, the originally detected differences between sample groups diminished. The results suggest that structural differences may not be reliably detected with clinical scanners. INTRODUCTION: Structural parameters of bone reflect its health status, but are highly dependent on the image resolution. We hypothesized that image resolution affects bone structural parameters differently in normal and osteoporotic trabecular bone. METHODS: Human trabecular bone samples from the iliac crest and the knee were analyzed (normal n = 11, osteoporotic n = 15) using a high-resolution microCT (14 or 18 um voxel sizes). Images were re-sampled to voxel sizes 1-16 times larger than the original image and thresholded with global or local adaptive algorithms. Absolute and normalized values of each structural parameter were calculated, and the effect of decreasing image resolution was compared between the normal and osteoporotic samples. RESULTS: Normal and osteoporotic samples had different (p < 0.05) absolute bone volume fractions. However, the normalized values showed that the osteoporotic samples were more prone to errors (p < 0.05) with increased voxel size. The absolute values of trabecular number, trabecular separation, degree of anisotropy, and structure model index were different between the groups at the original voxel size (p < 0.05), but at voxel sizes between 60 and 110 um, those differences were no longer significant. CONCLUSIONS: The results suggest that structural differences between osteoporotic and normal trabecular bone may not be reliably detected with clinical CT scanners providing image voxel sizes above 100 um. PMID- 20349044 TI - Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder. AB - We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg(-1)) 2-24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC(50) value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 microM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M(2) function is enhanced following streptozotocin treatment. PMID- 20349045 TI - Glycyl-glutamine (beta-endorphin(30-31)) inhibits morphine-induced dopamine efflux in the nucleus accumbens. AB - Glycyl-glutamine (Gly-Gln) is an endogenous dipeptide that is synthesized from beta-endorphin post-translationally. Previously, we showed that Gly-Gln prevents acquisition of morphine-conditioned place preference, a behavioral test of morphine reward, but does not interfere with morphine analgesia. In this study, we tested the hypothesis that Gly-Gln inhibits morphine reward by blocking morphine-induced dopamine efflux in the nucleus accumbens (NAc). Extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were sampled by microdialysis and analyzed by high-performance liquid chromatography with electrochemical detection. Guide cannulas were implanted in the right NAc and left lateral ventricle of male Sprague-Dawley rats stereotaxically. Approximately 24 h later, a microdialysis probe was inserted into the NAc and perfused at 1 microl/min. Gly Gln (1, 3, 30, or 100 nmol/5 microl) or saline was administered intracerebroventricularly, morphine (2.5 mg/kg) was injected intraperitoneally (i.p.) 2 min later, and extracellular dopamine and DOPAC were sampled at 20-min intervals. Morphine administration increased extracellular dopamine concentrations by approximately 600% within 40 min. Gly-Gln pretreatment inhibited the rise in extracellular dopamine in a dose-related manner; the lowest significantly inhibitory dose was 1 nmol. Gly-Gln also inhibited the morphine induced rise in extracellular DOPAC concentrations but did not affect extracellular dopamine or DOPAC in control animals. Gly-Gln (100 nmol/5 microl) prevented morphine-induced dopamine efflux in rats treated with morphine chronically (10 mg/kg, i.p. twice daily for 6 days), although it did not affect DOPAC concentrations significantly. These data support the hypothesis that Gly Gln abolishes the rewarding effect of morphine by inhibiting the ability of morphine to stimulate dopamine release in the NAc. PMID- 20349046 TI - NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities. AB - The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP 184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders. PMID- 20349047 TI - Atorvastatin reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation. AB - The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group II, a sham operation +10 mg/kg atorvastatin; group III, bilateral ovarian ischemia; and groups IV and V, bilateral ovarian ischemia +5 and 10 mg/kg atorvastatin before 30 min of ischemia, respectively (after a 3-h period of ischemia, the bilateral ovaries were surgically removed); group VI, 3-h period of ischemia followed by 3 h reperfusion; groups VII and VIII received 5 and 10 mg/kg atorvastatin, respectively, 2.5 h after the induction of ischemia, and at the end of a 3-h period of ischemia, bilateral vascular clips were removed and 3-h reperfusion continued. After the experiments, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity and levels of glutathione (GSH) and lipid peroxidation (LPO) were determined, and histopathological changes were examined in all rat ovarian tissue. Ischemia and I/R increased the LPO level and MPO activity while decreasing the SOD activity and GSH level significantly in comparison to the sham group. The 5- and 10-mg/kg doses of atorvastatin before ischemia and I/R reversed the trend in LPO level and MPO activity. The levels of SOD and GSH were decreased by ischemia and I/R. The administration of atorvastatin before ischemia and I/R treatments also reversed the trend in the SOD and GSH levels. In the I/R plus atorvastatin groups, although minimal vascular dilation in the ovary stoma and some degenerative cell clusters were seen, most of the cellular structures showed no pathological changes. Administration of atorvastatin is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries. PMID- 20349048 TI - Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration. AB - Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2) integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H (1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO 1/CO/guanosine 3'5'-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases. PMID- 20349049 TI - Cannabis constituents modulate delta9-tetrahydrocannabinol-induced hyperphagia in rats. AB - RATIONALE: The hyperphagic effect of Delta9-tetrahydrocannabinol (Delta9THC) in humans and rodents is well known. However, no studies have investigated the importance of Delta9THC composition and any influence other non-Delta9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified Delta9THC, synthetic Delta9THC (dronabinol), and Delta9THC botanical drug substance (Delta9THC-BDS), a Delta9THC-rich standardized extract comparable in composition to recreationally used cannabis. METHODS: Adult male rats were orally dosed with purified Delta9THC, synthetic Delta9THC, or Delta9THC BDS, matched for Delta9THC content (0.34-2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following Delta9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. RESULTS: All three Delta9THC substances tested induced significant hyperphagic effects at doses >or=0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified Delta9THC and Delta9THC-BDS. CONCLUSION: All Delta9THC compounds displayed classical Delta9THC effects on feeding, significantly increasing shortterm intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified Delta9THC and Delta9THC-BDS are due to non-Delta9THC cannabinoids present in Delta9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate Delta9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential. PMID- 20349050 TI - Dopamine D2 receptor occupancy by perospirone: a positron emission tomography study in patients with schizophrenia and healthy subjects. AB - RATIONALE: Perospirone is a novel second-generation antipsychotic drug with high affinity to dopamine D(2) receptor and short half-life of plasma concentration. There has been no investigation of dopamine D(2) receptor occupancy in patients with schizophrenia and the time course of occupancy by antipsychotics with perospirone-like properties. OBJECTIVE: We investigated dopamine D(2) receptor occupancy by perospirone in patients with schizophrenia and the time course of occupancy in healthy subjects. MATERIALS AND METHODS: Six patients with schizophrenia taking 16-48 mg/day of perospirone participated. Positron emission tomography (PET) scans using [(11)C]FLB457 were performed on each subject, and dopamine D(2) receptor occupancies were calculated. Moreover, baseline and three serial PET using [(11)C]raclopride were performed at 1.5, 8, and 25.5 h after administration of a single dose of 16 mg of perospirone on four healthy male subjects, and occupancy was calculated for each scan. RESULTS: Dopamine D(2) receptor occupancy in the temporal cortex of patients ranged from 39.6% to 83.8%. Especially, occupancy in two patients who took 16 mg of perospirone 2.5 h before PET was over 70%. Mean occupancy in the striatum of healthy subjects was 74.8% at 1.5 h, 60.1% at 8 h, and 31.9% at 25.5 h after administration. CONCLUSION: Sixteen milligrams of perospirone caused over 70% dopamine D(2) receptor occupancy near its peak level, and then occupancy dropped to about half after 22 h. The time courses of receptor occupancy and plasma concentration were quite different. This single dosage may be sufficient for the treatment of schizophrenia and might be useful as a new dosing schedule choice. PMID- 20349051 TI - Variation in the PTH gene, hip fracture, and femoral neck geometry in elderly women. AB - Parathyroid hormone (PTH) is a principal regulator of calcium homeostasis. Previously, we studied single-nucleotide polymorphisms present in the major genes in the PTH pathway (PTH, PTHrP, PTHR1, PTHR2) in relation to bone mineral density (BMD) and fracture incidence. We found that haplotypes of the PTH gene were associated with fracture risk independent of BMD. In the present study, we evaluated the relationship between PTH haplotypes and femoral neck bone size. Hip structure analysis and BMD of the femoral neck was assessed by DXA in elderly women from the Malmo Osteoporosis Prospective Risk Assessment study. Data on hip fracture, sustained as a result of low trauma, after the age of 45 years were also analyzed. Haplotypes derived from six polymorphisms in the PTH locus were analyzed in 750 women. Carriers of haplotype 9 had lower values for hip geometry parameters cross-sectional moment of inertia (P = 0.029), femoral neck width (P = 0.049), and section modulous (P = 0.06), suggestive of increased fracture risk at the hip. However, this did not translate into an increased incidence of hip fracture in the studied population. Women who suffered a hip fracture compared to those who had not had longer hip axis length (HAL) (P < 0.001). HAL was not significantly different among haplotypes. Polymorphisms in the PTH gene are associated with differences in aspects of femoral neck geometry in elderly women; however, the major predictor of hip fracture in our population was HAL, to which PTH gene variation does not contribute significantly. PMID- 20349052 TI - [13C]pantoprazole breath test as a predictor of the anti-platelet function of clopidogrel. AB - BACKGROUNDS/AIMS: Clopidogrel, a platelet inhibitor, is metabolized by cytochrome P450 2C19 (CYP2C19) to its active metabolite and, consequently, its anti-platelet efficacy is influenced by CYP2C19 activity. The aim of this study was to determine whether the [(13)C]pantoprazole breath test, a recently developed tool used to measure CYP2C19 activity, can predict the anti-platelet efficacy of clopidogrel. METHODS: Seventy healthy volunteers with different CYP2C19 genotypes received 100 mg of [(13)C]pantoprazole. Breath samples were collected at 10-min intervals for 60 min, and changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) from the baseline level were measured and expressed as a delta-over-baseline (DOB) ratio (per thousand). After a washout period of > 2 weeks, the subjects underwent a platelet aggregation test before and after dosing with 75 mg of clopidogrel for 7 days. The percentage inhibition of platelet aggregation (IPA, %) was then calculated. RESULTS: There was a statistically significant correlation between the area under the curve (AUC)(20-60 min) of the DOB and IPA at 4 h attained by clopidogrel. The mean AUC(20-60 min) of the DOB of the "low-responder" (IPA < 20%) group was significantly lower than that of the responder group (IPA > or = 20%). CONCLUSION: The results of our preliminary study suggest that the [(13)C]pantoprazole breath test can predict the anti platelet efficacy of clopidogrel. PMID- 20349053 TI - Nematode sbRNAs: homologs of vertebrate Y RNAs. AB - Stem-bulge RNAs (sbRNAs) are a group of small, functionally yet uncharacterized noncoding RNAs first described in C. elegans, with a few homologous sequences postulated in C. briggsae. In this study, we report on a comprehensive survey of this ncRNA family in the phylum Nematoda. Employing homology search strategies based on both sequence and secondary structure models and a computational promoter screen we identified a total of 240 new sbRNA homologs. For the majority of these loci we identified both promoter regions and transcription termination signals characteristic for pol-III transcripts. Sequence and structure comparison with known RNA families revealed that sbRNAs are homologs of vertebrate Y RNAs. Most of the sbRNAs show the characteristic Ro protein binding motif, and contain a region highly similar to a functionally required motif for DNA replication previously thought to be unique to vertebrate Y RNAs. The single Y RNA that was previously described in C. elegans, however, does not show this motif, and in general bears the hallmarks of a highly derived family member. PMID- 20349054 TI - Containment of extended length polymorphisms in silk proteins. AB - The spider silk gene family to the current date has been developed by gene duplication and homogenization events as well as conservation of crucial sequence parts. These evolutionary processes have created an amazing diversity of silk types each associated with specific properties and functions. In addition, they have led to allelic and gene variants within a species as exemplified by the major ampullate spidroin 1 gene of Nephila clavipes. Due to limited numbers of individuals screened to date little is known about the extent of these heterogeneities and how they are finally manifested in the proteins. Using expanded sample sizes, we show that sequence variations expressed as deletions or insertions of tri-nucleotides lead to different sized and structured repetitive units throughout a silk protein. Moreover, major ampullate spidroins 1 can quite dramatically differ in their overall lengths; however, extreme variants do not spread widely in a spider population. This suggests that a certain size range stabilized by purifying selection is important for spidroin 1 gene integrity and protein function. More than one locus for spidroin 1 genes possibly exist within one individual genome, which are homogenized in size, are differentially expressed and give a spider a certain degree of adaptation on silk's composition and properties. Such mechanisms are shared to a lesser extent by the second major ampullate spidroin gene. PMID- 20349055 TI - Lineage-specific duplication and loss of pepsinogen genes in hominoid evolution. AB - Fourteen different pepsinogen-A cDNAs and one pepsinogen-C cDNA have been cloned from gastric mucosa of the orangutan, Pongo pygmaeus. Encoded pepsinogens A were classified into two groups, i.e., types A1 and A2, which are different in acidic character. The occurrence of 9 and 5 alleles of A1 and A2 genes (at least 5 and 3 loci), respectively was anticipated. Respective orthologous genes are present in the chimpanzee genome although their copy numbers are much smaller than those of the orangutan genes. Only A1 genes are present in the human probably due to the loss of the A2 gene. Molecular phylogenetic analyses showed that A1 and A2 genes diverged before the speciation of great hominoids. Further reduplications of respective genes occurred several times in the orangutan lineage, with much higher frequencies than those occurred in the chimpanzee and human lineages. The rates of non-synonymous substitutions were higher than those of synonymous ones in the lineage of A2 genes, implying the contribution of the positive selection on the encoded enzymes. Several sites of pepsin moieties were indeed found to be under positive selection, and most of them locate on the surface of the molecule, being involved in the conformational flexibility. Deduced from the known genomic structures of pepsinogen-A genes of primates and other mammals, the duplication/loss were frequent during their evolution. The extreme multiplication in the orangutan might be advantageous for digestion of herbaceous foods due to the increase in the level of enzymes in stomach and the diversification of enzyme specificity. PMID- 20349056 TI - The 'wandering' Meckel diverticulum: an unusual scintigraphic finding. PMID- 20349057 TI - Contralateral hemimicrencephaly in neonatal hemimegalencephaly. AB - Identification of abnormalities in the contralateral hemisphere in patients with hemimegalencephaly is critical in their management. In this report, we present a 5-day-old neonate with hemimegalencephaly who demonstrated an enlarged ipsilateral cerebral hemisphere and diffuse volume loss in the contralateral hemisphere on conventional MR imaging sequences. The ipsilateral frontal white matter demonstrated relatively increased NAA, fractional anistropy, and cerebral blood volume values compared to published normative data. In addition, the white matter of the contralateral hemisphere demonstrated elevated lactate and increased mean diffusivity compared to published normative data, supporting the abnormal conventional MR findings. Advanced MR neuroimaging techniques may help further confirm and characterize abnormalities in the smaller contralateral hemisphere in neonatal hemimegalencephaly. PMID- 20349058 TI - Association between environmental microbiota and indigenous bacteria found in hemolymph, extrapallial fluid and mucus of Anodonta cygnea (Linnaeus, 1758). AB - Bivalves filter and accumulate large numbers of microorganisms present in the harvesting water. A complete understanding of the balance between Anodonta cygnea and the microbiota present in their surrounding environment remains incomplete. Therefore, the aim of this study was to quantify and identify the indigenous bacteria in the biological fluids of A. cygnea collected from Mira Lagoon in northern Portugal. The results showed Vibrio metschnikovii and Aeromonas sobria as the dominant groups. The median for total bacteria from mucus was 3.1 * 10(3) CFU g(-1), whereas the range in means from fluids was 1.5 * 10(2) to 6.5 * 10(2) CFU ml(-1). During the experimental work, Escherichia coli and enterococci were not detected in healthy A. cygnea. However, the periodic detection of E. coli and enterococci in Mira lagoon revealed its presence in the water. Our observations suggest that A. cygnea has the ability to filter and eliminate E. coli, present in the surrounding environment, through an active phagocytic process conducted by hemolymph circulating cells, the hemocytes. PMID- 20349059 TI - RNA interference targeting programmed death receptor-1 improves immune functions of tumor-specific T cells. AB - Adoptive cell transfer (ACT), either using rapidly expanded tumor infiltrating lymphocytes or T-cell receptor transduced peripheral blood lymphocytes, can be considered one of the most promising approaches in cancer immunotherapy. ACT results in the repopulation of the host with high frequencies of tumor-specific T cells; however, optimal function of these cells within the tumor micro environment is required to reach long-term tumor clearance. We and others have shown that ongoing anti-tumor immune responses can be impaired by the expression of ligands, such as PD-L1 (B7-H1) on tumor cells. Such inhibitory molecules can affect T cells at the effector phase via their receptor PD-1. PD-L1/PD-1 interaction has indeed been shown crucial in inducing T-cell anergy and maintaining peripheral tolerance. In order to maximize anti-tumor responses, antibodies that target the PD-1/PD-L1 axis are currently in phase I/II trials. Alternatively, a more refined approach could be the selective targeting of PD-1 in tumor-specific T cells to obtain long-term resistance against PD-1-mediated inhibition. We addressed whether this goal could be achieved by means of retroviral siRNA delivery. Effective siRNA sequences resulting in the reduction of surface PD-1 expression led to improved murine as well as human T-cell immune functions in response to PD-L1 expressing melanoma cells. These data suggest that blockade of PD-1-mediated T-cell inhibition through siRNA forms a promising approach to achieve long-lasting enhancement of tumor-specific T-cell function in adoptive T-cell therapy protocols. PMID- 20349060 TI - Bortezomib, doxorubicin, and dexamethasone combination therapy followed by thalidomide and dexamethasone consolidation as a salvage treatment for relapsed or refractory multiple myeloma: analysis of efficacy and safety. AB - We conducted a phase 2 study with bortezomib, doxorubicin, and dexamethasone (PAD) followed by thalidomide and dexamethasone (TD) in patients with relapsed multiple myeloma (MM). Forty patients were enrolled between November 2005 and October 2007, with follow-up continuing until January 2009. Efficacy could be assessed in 37 patients. The overall response rate to PAD followed by TD was 83.6%: complete response 51.4%, near-complete response 13.4%, very good partial remission 5.4%, and partial response 13.4%. The median follow-up was 27 months (range 13-39). The median progression-free survival (PFS) from the start of treatment was 18 months (95% CI, 9.7-26.2 months), with a 1-year PFS rate of 56.9% and 3-year PFS rate of 25.7%. Median overall survival was 35.1 months (95% CI, 18.5-51.7), with a 1-year survival rate of 75% and 3-year survival rate of 27.3%. One hundred seventy-eight PAD cycles (median 6, range 1-6) in 38 patients were assessable for safety. The most common hematologic toxicity was thrombocytopenia, with grade 3-4 in 35.8%. Sensory neuropathy occurred at grade 2 in 26.3% and grade 3 in 10.3%. Two hundred TD treatment cycles (median 4, range 0 12 cycles) were administered. Most adverse events were of mild degree and manageable. PAD followed by TD in patients with relapsed MM is very effective and tolerable. PMID- 20349061 TI - [Littoral cell angioma of the spleen. Association with colon and hepatocellular carcinoma]. AB - Littoral cell angioma is a rare vascular tumor of the spleen. An increased association with concomitant malignancies has been described. We report the case of a 67-year-old man suffering from colon carcinoma and presenting with a tumor of the spleen which could be seen using radiography. Splenectomy was performed and histology revealed a 2.1 cm vascular tumor with a characteristic immunophenotype (CD31/68+). In addition a hepatocellular carcinoma was found. Due to the relationship with malignant tumors littoral cell angioma should be considered in every case of a splenic tumoral space-occupying mass, particularly in carcinoma patients. PMID- 20349062 TI - [Gastric MALT-type lymphoma. Pathology, pathogenesis, diagnostics and therapy]. AB - Helicobacter pylori infection plays a central role in the development of gastric MALT-type (mucosa-associated lymphoid tissue) lymphoma. Infection results in chronic H. pylori gastritis and stimulates together with antigens or autoantigens proliferation of B-lymphocytes which is the basis for the neoplastic transformation. Histology of MALT-type lymphoma is architecturally similar to the physiological MALT. Invasion and destruction of the gastric epithelium with development of so-called lympho-epithelial lesions is the most important diagnostic criterion. Cytologically MALT-lymphoma resembles centrocytes and monocytes. For definitive lymphoma diagnosis and for the differential diagnosis from other small cell lymphomas in the stomach immunohistochemistry can be helpful. The phenotype of MALT-type lymphoma is identical to non-neoplastic B lymphocytes of the marginal zone (CD20+, CD5-, CD10- and CD23-). Individual therapy is strongly dependent from histological type and lymphoma stadium. Therapy modalities are H. pylori eradication, radiochemotherapy, surgery or a combination of these. Aim of the therapy is the complete lymphoma regression and cure of the disease. PMID- 20349063 TI - [Tubular adenoma of the stomach with special reference to the Japanese criteria and pyloric gland adenoma]. AB - The term gastric adenoma usually refers to a flat adenoma of the intestinal type. Adenomas of the gastric type, so-called pyloric gland adenomas (PGA), which was first characterized by German and Japanese pathologists in 1990, have been regarded as exceptional until recently. In 2003, we first reported systematic clinical pathological analyses of PGA, demonstrating its unstable and precancerous nature. American gastrointestinal pathologists have finally recognized this disease entity in 2009. In this article we introduce the Japanese criteria of the gastric adenoma and review and discuss the clinical pathological and molecular aspects of PGAs. PMID- 20349064 TI - [New and proven methods in gastric pathology]. PMID- 20349065 TI - Rituximab and leflunomide for Wegener's granulomatosis: a long-term follow-up. PMID- 20349066 TI - Patterns of preventive health services in rheumatoid arthritis patients compared to a primary care patient population. AB - To determine the proportion of rheumatoid arthritis (RA) patients receiving preventive health care according to US Preventive Services Task Force recommendations compared with a community-based population sample, with emphasis on dyslipidemia testing, given the increased risk of cardiovascular disease (CVD) in RA patients. Patients with RA (ICD-9 code 714.0 at >=2 office visits with a rheumatologist) and a primary care physician (PCP) at the Geisinger Health System (GHS) were identified through electronic health records. The records were searched back from 3/31/08 for the length of time required to satisfy each outcome measure. Percentages were compared with population testing rates using the Pearson Chi-square test. Eight hundred and thirty-one RA patients were compared to 169,476 subjects with a PCP at GHS, stratified by gender and age. Patients with RA were more likely to have had dyslipidemia and osteoporosis testing compared with the general population (86 vs. 75 and 75 vs. 55%, respectively, P < 0.0001 for both). The proportion of RA patients receiving breast and cervical cancer testing was similar to the general population. The majority (79%) of lipid testing was ordered by PCPs. Those RA patients with recommended lipid testing had more traditional CVD factors (hypertension, diabetes, coronary artery disease). RA patients are screened more than the general population for two RA-related co-morbidities, i.e. dyslipidemia and osteoporosis. The RA patients with traditional cardiovascular risk factors are more likely to be tested for dyslipidemia. Further work is warranted to improve testing for modifiable CVD risk factors in this group with multiple co morbidities. PMID- 20349067 TI - Successful treatment with very low-dose etanercept in a patient with etanercept induced liver dysfunction. PMID- 20349068 TI - Development of interstitial pneumonia in a patient with rheumatoid arthritis induced by isoniazid for tuberculosis chemoprophylaxis. AB - Here, we report a 56-year-old patient with rheumatoid arthritis (RA) who had been treated with methotrexate and sulfuasalazine, but the disease activity remained high. Therefore, we planned TNF-blocker treatment for this patient. A tuberculin skin test was positive, we started anti-tuberculosis (TB) chemoprophylaxis with isoniazid (INH). However, liver dysfunction was appeared after 2 weeks from the start of INH. Therefore, we discontinued INH transiently and tried the desensitization of INH. However, interstitial pneumonia was developed 2 weeks after the re-start of INH, we decided to stop the INH prophylaxis. Interstitial pneumonia was improved by corticosteroid treatments. This case report shows that INH-induced IP can be occurred during the course of anti-TB chemoprophylaxis in patients with RA. PMID- 20349069 TI - Systemic lupus erythematosus pregnancies: the Sarawak experience and review of lupus pregnancies in Asia. AB - We performed a cross-sessional study of all systemic lupus erythematosus (SLE) pregnancies during a 4-year period (2006-2009) to describe the clinical features, maternal and foetal outcomes in our centre. There were 48 pregnancies in 44 women with SLE. Our patients have a mean age of 30.0 years (SD 6.36) and a mean disease duration of 40.67 months (SD 48.23). Our patients have complicated pregnancies: 32.7% have SLE flares, 17.3% have preeclampsia and 48.9% needed caesarean sections. There were 20.0% foetal losses and 17.8% preterm deliveries in our patients. SLE flares contributed to 60.0% of foetal losses in our patients. Lupus pregnancies in our centre generally have a good maternal and foetal outcome comparable to developed countries in Asia. The low incidence of APS, the high usage of hydroxychloroquine and the high SLE remission rate in our patients prior to conceptions contributed to the good outcome. PMID- 20349070 TI - Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare but extremely disabling genetic disease of the skeletal system. This disease is characterized by progression of heterotopic ossification within skeletal muscles, ligaments and tendons. Most patients with FOP are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures such as biopsy that can cause lifelong disability. Almost all of the patients have some peculiar congenital anomalies, including short great toes, hallux valgus, short thumbs and hypoplasia of digital phalanges. These congenital defects support the diagnosis of FOP, but are not constantly observed in the totality of patients. If necessary, genetic studies can be performed to confirm the diagnosis. Once diagnosed, patients should be advised in order to avoid unnecessary traumas, surgical procedures, biopsies, intramuscular injections and vaccinations. Here, we describe a patient with FOP without characteristic congenital skeletal anomalies. PMID- 20349071 TI - TNF-alpha antagonist therapy modify the tuberculin skin test response. AB - Tumour necrosis factor-alpha (TNF-alpha) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-alpha antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-alpha antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5 mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0-4 mm) and 95 (52%) had a positive (>= 5 mm) TST response at initial evaluation. The TST responses were converted from negative at initial visit to positive at 1-year repeat in 26 (30%) patients. A significant increase was observed in the diameters of TST that were repeated on the first year of TNF-alpha antagonist treatment (9.15 +/- 0.55) compared to their initial diameters (6.60 +/- 0.51) (P < 0.001). Increased TST responses in patients receiving TNF-alpha antagonists may be associated with the restoration of suppressed immune reactivity against TB antigens with the decreased disease activity. The meaning of TST conversion in the definition of latent TB infection and the need for chemoprophylaxis in these patients remains to be answered by further studies. PMID- 20349072 TI - Atherosclerosis and endothelial dysfunction in patients with ankylosing spondylitis. AB - Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease characterized primarily by axial joint involvement, sacroiliitis and various extra-articular manifestations. High cardiovascular mortality in AS has led many researchers to investigate possible risk factors involved with cardiovascular disease in these patients. This review summarizes published data concerning endothelial dysfunction and atherosclerosis in patients with AS. The author discusses current limitations and problems related to a better assessment of these two possible changes in AS. PMID- 20349073 TI - Extraperitoneal laparo-endoscopic single-site radical prostatectomy: first experience. AB - OBJECTIVES: Up to now, laparo-endoscopic single-site surgery (LESS) represents the closest surgical technique to scar-free surgery. The objective of the study is to report the first clinical experience with a LESS endoscopic extraperitoneal radical prostatectomy. MATERIALS AND METHODS: A 74-year-old man presented with a clinically localized prostate cancer (PSA 9.9, Gleason score 3 + 3 = 6). Consent was obtained for LESS radical prostatectomy. After a 2-cm midline subumbilical incision, the preperitoneal space was created using a balloon trocar. Then, the TriportTM was introduced. Using straight, as well as pre-curved instruments, the radical prostatectomy was performed in accordance with the well-described technique of endoscopic extraperitoneal radical prostatectomy. RESULTS: The procedure was completed successfully. Overall operation time was 290 min. The estimated blood loss was 100 mL. There were no intra-or postoperative complications. No additional ports were required. On the 6th postoperative day, a cystogram was performed. No leak was demonstrated, enabling catheter removal. Histopathology revealed bilateral adenocarcinoma with no extracapsular extension and a Gleason sum of 3 + 4 = 7. Surgical margins were negative. Two weeks postoperatively, the patient reported the use of only one safety pad for continence. CONCLUSIONS: An extraperitoneal laparo-endoscopic single-site radical prostatectomy is technically challenging but can be accomplished. A multi instrument port and purpose-built equipment are mandatory. The oncologic outcome was not compromised. Additional short- and long-term studies are necessary to clarify the role of LESS in radical prostatectomy regarding the oncologic and functional outcome as well as the potential benefits like reduced tissue trauma and pain. PMID- 20349074 TI - Modified concept for radioisotope-guided sentinel lymph node dissection in prostate cancer. AB - PURPOSE: To present a modified concept for sentinel lymph node (SLN)-guided pelvic lymph node dissection in prostate cancer. METHODS: A total of 463 patients with histologically proven prostate cancer underwent SLN-guided lymph node dissection. The day before surgery patients received intraprostatic injection of Tc-99 m-labeled nanocolloid (Tc-NC) under transrectal ultrasound guidance. At the time of surgery, the lymph nodes of the obturator fossa were dissected routinely in all patients. After meticulous testing with a handheld gamma probe, all lymphatic tissues in predefined anatomic regions (external iliac, internal iliac, common iliacal and presacral) with Tc-NC uptake were additionally resected. RESULTS: In 146 (12.8%) patients, SLN were located exclusively in the obturator fossa, but 317 patients (87.2%) underwent resection of additional sentinel regions. In 28 (6.1%) patients, 62 lymph node metastases were detected, and 32 (51.6%) of these were located outside the obturator fossa. Eight (28.6%) patients displayed lymph node metastases exclusively outside the obturator fossa and had been resected only because of positive SLN probing. CONCLUSIONS: The obturator fossa comprises the major landing site of lymph node metastases, but more than half of the metastases are located outside this anatomic region. Routine resection of the obturator fossa with additional resection of positive sentinel regions improves staging accuracy compared to resection of the obturator fossa only. PMID- 20349075 TI - Oncological outcome after incidental perforation in radical rectal cancer surgery. AB - PURPOSE: Identification of risk factors of poor oncological outcome in rectal cancer surgery is of utmost importance. This study examines the impact of incidental perforation on the oncological outcome. METHODS: Using the Swedish Rectal Cancer Registry, patients were selected who received major abdominal surgery for rectal cancer between 1995 and 1997 with registered incidental perforation. A control group was also selected for analysis of the oncological outcome after 5-year follow-up. Multivariate analysis was performed. Registry data were validated, and additional data were supplemented from medical records. RESULTS: After validation and exclusion of non-radically operated patients, 118 patients with incidental perforation and 155 controls in TNM stages I-III were included in the analysis. The rate of local recurrence (LR) [20% (23/118) vs. 8% (12/155) (p = 0.007)] was significantly higher among patients with perforation, whereas the rates of distant metastasis [27% (32/118) vs. 21% (33/155) (p = 0.33)] and overall recurrence (OAR) [35% (41/118) vs. 25% (38/155) (p = 0.087)] were not significantly different between the groups. Overall as well as cancer specific 5-year survival rates were significantly reduced for the patients with perforation [44 vs. 64% (p = 0.002) and 66 vs. 80% (p = 0.026), respectively]. In the multivariate analysis, perforation was a significant risk factor of increased rates of LR and OAR as well as reduced 5-year overall and cancer-specific survival. CONCLUSIONS: Incidental perforation in rectal cancer surgery is an important risk factor of poor oncological outcome and should be considered in the discussion concerning postoperative adjuvant treatment as well as the follow-up regime. PMID- 20349076 TI - Office hysteroscopy: current trends and potential applications: a critical review. AB - Office hysteroscopy is an excellent method of identifying and treating intracavitary uterine lesions. It has become easy to learn and perform; as an aid of modern technological applications, it is safe, accurate, provides immediate results under direct visualisation, and offers the additional benefit of histological confirmation and the discomfort of patients is minimal. We applied an extended literature search to explore the special features and details of the technique itself, as it evolved since it first appeared 30 years back. Our initial goal was to examine potential changes/improvements of the modality, in terms of the instrumentation used and the technique itself, the indications of use, its incorporation in daily practice, and patients' and clinicians' acceptability. PMID- 20349077 TI - Axonal damage in acute cerebral infarction showing ADC reduction. PMID- 20349079 TI - Guillain-Barre syndrome after short-course efalizumab treatment. PMID- 20349080 TI - The use of silicone oil-RMN3 (Oxane HD) as heavier-than-water internal tamponade in complicated inferior retinal detachment surgery. AB - BACKGROUND: Conventional silicone oil provides suboptimal support of the inferior retina. In this study we evaluated the efficacy of Oxane HD in the management of complex retinal detachments involving lower quadrants of the retina. METHODS: A prospective, interventional, comparative study. Eighteen patients were recruited. Treatment outcomes were compared with a historical control group of 14 patients. Patients with grade C3 PVR or greater and inferior retinal breaks, recurrent inferior retinal detachments (with or without PVR) and giant retinal tears were included. In those patients who re-detached under heavy silicone oil (n = 4), retro-oil epiretinal membranes (ERMs) were obtained at the time of subsequent surgery to analyse the immunopathological response to oxane HD. Immunohistochemistry was used to detect glia, retinal pigment epithelium cells (RPE), macrophages, T lymphocytes, or neural elements in the tissue using well characterised monoclonal antibodies. RESULTS: Retinal attachment of the posterior pole following removal of silicone oil was achieved in 66.6% of the treatment group (n = 12) and 64.3% of controls (n = 9) (p = 1.0). Post-operative PVR developed in five patients in the treatment group (27.8%) and five control patients (35.8%). Following removal of silicone oil, residual oil was observed in 27.8% of the treatment group and 7.1% of controls. Median visual acuity, 3 months following removal of silicone oil, was 2.0 (IQR 0.9-2.0) in the treatment group and 1.0 (IQR 0.6-1.8) in the control group. Complications in the treatment group included, hypotony (n = 3), uveitis (n = 2), glaucoma (n = 1). All ERMs analysed demonstrated microscopic appearances typical of PVR. The membranes were fibrocellular in nature, contained RPE and glial cells, and variable amounts of intracellular and extracellular pigment. In addition, all had a dense infiltrate of vacuolated (presumed oil-filled) macrophages. CONCLUSION: We failed to observe an advantage following the use of Oxane HD in the treatment of inferior retinal detachments. Moreover, Oxane HD was difficult to remove and was associated with a higher incidence of complications. PMID- 20349081 TI - Matrix metalloprotease-3 and tissue inhibitor of metalloprotease-1 mRNA and protein levels are altered in response to traumatic skeletal muscle injury. AB - The purpose of this study was to characterize the time course of matrix metalloprotease-3 (MMP-3) and tissue inhibitor of metalloprotease-1 (TIMP-1) expression in mouse tibialis anterior (TA) muscle post-injury. Mice were anesthetized, the TA muscle exposed, and injury induced by applying a cold steel probe (-79 degrees C) to the muscle for 10 s. Muscle was collected from uninjured and injured legs at 3, 10, 24, 48, and 72 h post-injury. qRT-PCR, immunoblotting, and immunohistochemistry were used to quantify/localize MMP-3 and TIMP-1. MMP-3 transcripts increased 19- and 12-fold, 10 and 24 h post-injury (p < 0.01), respectively. TIMP-1 transcript levels increased 9-, 34-, and 60-fold, 10, 24, and 48 h post-injury (p = 0.01), respectively, with a subsequent decrease 72 h post-injury (p < 0.01). Protein levels of the pro-form of MMP-3 increased within 3 h post-injury and remained elevated (p < 0.05). Active MMP-3 decreased over time, reaching a 72% decrease 72 h post-injury (p < 0.05). TIMP-1 protein decreased 75% within 3 h post-injury, returning to baseline by 72 h post-injury. In response to injury, injured skeletal muscle preferentially produces increased levels of the latent form of the MMP-3 protein with a concomitant decrease in the active form, and a significant decrease in TIMP-1 expression. The altered pattern of MMP-3/TIMP-1 expression may be due to alterations in post-transcriptional mechanisms that are responsible for specific regulation of the MMP-3/TIMP-1 system. These data suggest that there is a disproportionate regulation of the MMP 3/TIMP-1 system following traumatic injury and this response may contribute to impaired extracellular matrix remodeling. PMID- 20349082 TI - The energetics of cycling on Earth, Moon and Mars. AB - From 1885, technological improvements, such as the use of special metal alloys and the application of aerodynamics principles, have transformed the bicycle from a human powered heavy transport system to an efficient, often expensive, object used to move not only in our crowded cities, but also in leisure activities and in sports. In this paper, the concepts of mechanical work and efficiency of cycling together with the corresponding metabolic expenditure are discussed. The effects of altitude and aerodynamic improvements on sports performances are also analysed. A section is dedicated to the analysis of the maximal cycling performances. Finally, since during the next decades the return of Man on the Moon and, why not, a mission to Mars can be realistically hypothesised, a section is dedicated to cycling-based facilities, such as man powered short radius centrifuges, to be used to prevent cardiovascular and skeletal muscle deconditioning otherwise occurring during long-term exposure to microgravity. PMID- 20349083 TI - Comparative molecular and biochemical characterization of segmentally duplicated 9-lipoxygenase genes ZmLOX4 and ZmLOX5 of maize. AB - Lipoxygenases (LOXs) catalyze hydroperoxidation of polyunsaturated fatty acids (PUFAs) to form structurally and functionally diverse oxylipins. Precise physiological and biochemical functions of individual members of plant multigene LOX families are largely unknown. Herein we report on molecular and biochemical characterization of two closely related maize 9-lipoxygenase paralogs, ZmLOX4 and ZmLOX5. Recombinant ZmLOX5 protein displayed clear 9-LOX regio-specificity at both neutral and slightly alkaline pH. The genes were differentially expressed in various maize organs and tissues as well as in response to diverse stress treatments. The transcripts of ZmLOX4 accumulated predominantly in roots and shoot apical meristem, whereas ZmLOX5 was expressed in most tested aboveground organs. Both genes were not expressed in untreated leaves, but displayed differential induction by defense-related hormones. While ZmLOX4 was only induced by jasmonic acid (JA), the transcripts of ZmLOX5 were increased in response to JA and salicylic acid treatments. ZmLOX5 was transiently induced both locally and systemically by wounding, which was accompanied by increased levels of 9 oxylipins, and fall armyworm herbivory, suggesting a putative role for this gene in defense against insects. Surprisingly, despite of moderate JA- and wound inducibility of ZmLOX4, the gene was not responsive to insect herbivory. These results suggest that the two genes may have distinct roles in maize adaptation to diverse biotic and abiotic stresses. Both paralogs were similarly induced by virulent and avirulent strains of the fungal leaf pathogen Cochliobolus carbonum. Putative physiological roles for the two genes are discussed in the context of their biochemical and molecular properties. PMID- 20349084 TI - Antitumoral and antimetastatic effects of metronomic chemotherapy with cyclophosphamide combined with celecoxib on murine mammary adenocarcinomas. AB - PURPOSE: Metronomic chemotherapy (MCT) refers to the chronic and equally spaced administration of low doses of different chemotherapy drugs, without extended interruptions. Previously, we demonstrated the antitumor effect of MCT with cyclophosphamide (Cy) in a mouse mammary adenocarcinoma model. Herein, we investigated the therapeutic efficacy of metronomic Cy combined with celecoxib (Cel) in two murine mammary adenocarcinoma models. METHODS: Mice were s.c. challenged with M-234 p or M-406 mammary tumors and from day 5 or 8 on, respectively, treated with: (I) no treatment (controls); (II) Cy in the drinking water (25-30 mg/kg body weight/day); (III) Cel (30 mg/kg p.o.), five times/week; (IV) treated as II + III. Mice challenged i.v. with M-234 p or M-406 tumor cells received, on day 3, the same treatments. RESULTS: We found that MCT with Cy plus Cel inhibited tumor growth decreased lung metastases, and increased the median survival time, in both tumor models, having very low toxicity. MCT with Cy combined with Cel was more effective than each monotherapy. CONCLUSIONS: The therapeutic benefits of combined MCT with cyclophosphamide plus celecoxib on mammary adenocarcinomas together with its very low toxicity profile warrant further study in an attempt to make the translation into the clinic. PMID- 20349085 TI - Expression of Sox2 in human ovarian epithelial carcinoma. AB - OBJECTIVES: The aim of this study was to investigate the expression of Sox2, a transcription factor, in a series of benign, borderline, and malignant ovarian tumors and to evaluate whether Sox2 expression levels correlate with clinicopathological characteristics in ovarian epithelial carcinoma. METHODS: This study investigated immunohistochemical expressions of Sox2 in 43 species of normal ovarian epithelia, 284 species of serous epithelial lesions, and 164 species of mucinous epithelial lesions to assess their clinicopathological relevance. RESULTS: Immunohistochemical results showed that the positive ratio of Sox2 expression gradually increased from benign and borderline to malignant ovarian tumors; 55.81% of normal ovarian epithelia, ~65% of serous and mucinous cystadenoma, ~70% of borderline serous and mucinous cystadenoma, and ~91% of serous and mucinous cystadenocarcinoma expressed Sox2, respectively. However, there was no significant correlation between Sox2 expression and the age and level of CA125 in patients with either serous or mucinous tumors. Positive correlations between Sox2 expression levels and FIGO stage or pathological stage were identified in both serous and mucinous cystadenocarcinoma samples. CONCLUSION: The expression level of Sox2 in human ovarian tumors was directly proportional to their degree of malignancy, implying that Sox2 overexpression may be closely related to the malignant transformation of ovarian tumors. PMID- 20349086 TI - A BOD monitoring disposable reactor with alginate-entrapped bacteria. AB - Biochemical oxygen demand (BOD) is a measure of the amount of dissolved oxygen that is required for the biochemical oxidation of the organic compounds in 5 days. New biosensor-based methods have been conducted for a faster determination of BOD. In this study, a mathematical model to evaluate the feasibility of using a BOD sensor, based on disposable alginate-entrapped bacteria, for monitoring BOD in situ was applied. The model considers the influences of alginate bead size and bacterial concentration. The disposable biosensor can be adapted according to specific requirements depending on the organic load contained in the wastewater. Using Klein and Washausen parameter in a Lineweaver-Burk plot, the glucose diffusivity was calculated in 6.4 * 10(-10) (m2/s) for beads of 1 mm in diameter and slight diffusion restrictions were observed (n = 0.85). Experimental results showed a correlation (p < 0.05) between the respirometric peak and the standard BOD test. The biosensor response was representative of BOD. PMID- 20349087 TI - Proficiency-based Fundamentals of Laparoscopic Surgery skills training results in durable performance improvement and a uniform certification pass rate. AB - BACKGROUND: The authors have previously documented a 100% certification pass rate immediately after a proficiency-based skills training curriculum for the Fundamentals of Laparoscopic Surgery (FLS) program. This study aimed to determine the durability of skills acquired after initial training. METHODS: For this study, 21 novice medical students were enrolled in institutional review board (IRB)-approved protocols at two institutions. As previously reported, all the participants successfully completed a structured proficiency-based training curriculum by practicing the five FLS tasks in a distributed fashion over a 2 month period. Pre- and posttesting was conducted, and standard testing metrics were used. The participants were recruited for repeat testing 6 months (retention 1) and 1 year (retention 2) after initial curriculum completion. Of the original 21 students, 15 (10 at University of Texas Southwestern and 5 at Uniformed Services University) were available and agreed to participate. The participants had no additional skills lab training and minimal clinical laparoscopic exposure. RESULTS: None of the 15 participants demonstrated proficiency at the initial pretest (mean score, 146 +/- 65), and performance showed significant improvement (p < 0.001) at the posttest (469 +/- 20). The participants retained a very high level of performance at retention 1 (437 +/- 39; 93% retention of the posttest score) and retention 2 (444 +/- 55; 95% retention of the posttest score). Their performance at both retention testing-intervals was sufficient for passing the certification exam (270 cutoff score for passing) with a comfortable margin. There were no significant differences in performance between the two institutions at any time points. CONCLUSION: The proficiency-based FLS skills curriculum reliably results in a high level of skill retention, even in the absence of ongoing simulator-based training or clinical experience. This curriculum is suitable for widespread implementation. PMID- 20349088 TI - Routine postoperative upper gastrointestinal fluoroscopy is unnecessary after laparoscopic adjustable gastric band placement. AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has become an accepted procedure for weight loss surgery, particularly due to fewer early complications and decreased mortality in comparison to other bariatric procedures. Many centers use postoperative upper gastrointestinal fluoroscopy (UGI) to ensure stomal patency and gastric integrity at the banding site. However, UGI increases cost and may increase length of stay due to availability. The purpose of this study is to determine whether routine UGI after LAGB is necessary for detection of early complications. METHODS: A prospective database of 200 LAGBs performed by a single surgeon over 3 years was reviewed retrospectively. All patients underwent UGI 2 24 h after surgery. RESULTS: Mean age was 43, mean BMI was 45, and mean operative time was 44 min. Forty-four percent of patients stayed overnight. All postoperative UGI results were normal. Six percent underwent intraoperative instillation of methylene blue due to procedural difficulty with no leaks identified. These patients on average were 5 years older ( p< 0.01) and had an operative time 23 min longer (p < 0.01). Differences in gender and BMI were not statistically significant. One patient (0.5%), who had a normal methylene blue test and normal UGI, returned within 2 days with a gastric perforation requiring band explant and gastric repair. CONCLUSIONS: We conclude that routine UGI after LAGB is not necessary based on a 0% stomal obstruction rate and detection of not a single gastric leak. Elimination of routine postoperative UGI will decrease cost and length of hospital stay. We suggest a selective approach for those patients at increased risk of early postoperative complications, including those having intraoperative methylene blue instillation, increased length of operation, and increased age. PMID- 20349089 TI - Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model. AB - BACKGROUND: Coating prosthetic for hernia repair with a patient's own cells could improve biocompatibility by decreasing inflammation and adhesion formation and by increasing tissue ingrowth and resistance to infection. The objective of this study was to prove the feasibility of prosthetic coating with stem cells and to assess its resistance to adhesion formation when implanted in an animal model. METHODS: Adult Lewis rat bone marrow stem cells were harvested and cultured. Stem cells were then implanted on three different prosthetics. The prosthetic with the best stem cell adherence was implanted intraperitoneally into six adult rats. Untreated prosthetic was implanted in control animals (n = 12). After 2 weeks, intra-abdominal adhesions were graded using an adhesion scoring scale by two surgeons who were blinded to the animal group. Data were analyzed using the Wilcoxon rank-sum test. RESULTS: Stem cells demonstrated the best adherence and growth on polyglactin prosthetics. After implantation, the stem cell-coated polyglactin prosthetic had <25% of its surface area covered with adhesions in five (83%) samples, whereas the control polyglactin group had only one sample (8.3%) with <25% adhesions, and seven of its samples (58.3%) had >50% surface area adhesions (p < 0.05). CONCLUSIONS: The feasibility of hernia prosthetic coating with stem cells was demonstrated. Furthermore, stem-cell coated polyglactin prosthetic exhibited improved biocompatibility by decreasing adhesion formation in an animal model. Further study is needed to determine the factors that promote stem cell adherence to prosthetics and the in vivo prosthetic biomechanics after stem cell coating. This work is underway in our laboratory. PMID- 20349090 TI - Laparoendoscopic rendezvous: an effective alternative to a failed preoperative ERCP in patients with cholecystocholedocholithiasis. AB - BACKGROUND: Although the ideal management of cholelithiasis and concomitant choledocholithiasis is controversial, the two-stage approach [endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, and common bile duct (CBD) clearance followed by laparoscopic cholecystectomy] is the most popular treatment regimen worldwide. However, sometimes ERCP fails to solve the problem of choledocholithiasis preoperatively. The aim of this study was to evaluate the use of intraoperative ERCP using the laparoendoscopic "rendezvous" technique in patients in whom preoperative ERCP has failed or was not possible to attempt. METHODS: Twenty-two patients (13 female, nine male), in whom ERCP failed or was not possible to be performed as a separate procedure before laparoscopic cholecystectomy, were treated with the one-stage approach of intraoperative ERCP during laparoscopic cholecystectomy using the so-called laparoendoscopic "rendezvous" technique. RESULTS: The one-stage approach was completed successfully in a median time of 110 min (range = 75-160 min) in 21 cases; however, in two cases the wire introduced via the cystic duct could not be advanced through Vater's ampulla into the duodenum and the CBD was cannulated from the endoscopic route, in the usual way. There was no mortality or morbidity and most patients were discharged within 48 h after the procedure. CONCLUSION: The laparoendoscopic "rendezvous" is a valuable alternative in treating patients with cholecystocholedocholithiasis. It appears to be a reliable method when preoperative ERCP fails to clear the CBD, while it also offers a one-stage solution to the problem. PMID- 20349091 TI - Learning curve of assistants in laparoscopic colorectal surgery: overcoming mirror imaging. AB - BACKGROUND: Laparoscopic colorectal resection is widely used because of its safety and effectiveness compared with conventional surgery; however, surgical assistants find it difficult to perform this surgery in mirror image. This study aimed to evaluate assistants' learning curves in laparoscopic colorectal surgery. METHODS: The subjects were three fellows who began their surgical fellowship training at the Center for Colorectal Cancer of the National Cancer Center, Korea, during 2008. We analyzed the data from 145 laparoscopic colorectal surgeries in which these assistants participated. A learning curve was generated for each assistant using the moving average method to assess the execution time and the error rate for grasping tissue. RESULTS: Assistants A, B, and C participated in 50, 45, and 50 laparoscopic colorectal surgeries, respectively. Learning curves indicated that the execution time reached a steady state after 38 cases for Assistant A, 29 cases for Assistant B, and 24 cases for Assistant C. Based on a decline in the error rate, the steady state was reached after approximately 44 cases for Assistant A, 32 cases for Assistant B, and 41 cases for Assistant C. CONCLUSION: Analysis of the assistants' learning curves suggests that under reverse alignment conditions, assistants require participation in 30 40 cases before gaining surgical competence. These results have implications for training assistants for laparoscopic colorectal surgery. PMID- 20349092 TI - Are nurses and physicians able to assess which strategies adolescents recently diagnosed with cancer use to cope with disease- and treatment-related distress? AB - PURPOSE: It was examined whether nurses and physicians are able to identify whether adolescents with cancer have used certain strategies to cope with disease and treatment-related distress. METHOD: Adolescents (N = 48) were asked whether they had used a number of strategies to cope with disease- and treatment-related distress and, if so, the extent to which they had used these. Nurses and physicians were asked to answer the same questions on behalf of a certain adolescent. RESULTS: Nurses overestimate the extent to which adolescents use strategies to cope with distress, and neither nurses nor physicians, physicians somewhat more, are successful in identifying the extent to which certain adolescents use strategies. CONCLUSION: Health-care staff's possibilities to assess how patients cope with disease- and treatment-related distress should be increased. A number of changes in education and the organization of clinical care, especially with regard to assessing patients' needs, are suggested. PMID- 20349093 TI - The AD-type ectomycorrhizas, one of the most common morphotypes present in truffle fields, result from fungi belonging to the Trichophaea woolhopeia species complex. AB - Belowground ectomycorrhizal communities are often species rich. Characterization of the ectomycorrhizas (ECMs) underneath native truffle areas and/or cultivation sites is particularly relevant to identifying fungal species that might interfere with or promote truffle propagation and fruiting. Fungal identification at the genus/species level can now be achieved by combining detailed morphological and anatomical descriptions with molecular approaches. In a survey of the mycorrhizal biodiversity of Tuber melanosporum orchards and inoculated host plants in nurseries, we repeatedly sampled ECMs with morphological features resembling those of the ECMs widely known as the AD type. Despite the fact that the AD type is regarded as one of the most competitive fungal species towards Tuber spp., its taxonomical rank has yet to be resolved. By analyzing the 28S and internal transcribed spacer (ITS) rDNA regions, here, we show that AD-type ECMs result from host plant colonization by the pyronemataceous species Trichophaea woolhopeia. Further to this, the 28S and ITS phylogenetic trees built from the AD type ECMs analyzed sustain the hypothesis that T. woolhopeia is a species complex. PMID- 20349095 TI - Multivariate analysis of the influence of patient-, tumor-, and management related factors on the outcome of surgical therapy for facial basal-cell carcinoma. AB - PURPOSE: This retrospective, case-control study aimed at evaluating the influence of patient-, tumor-, and management-related factors on the outcome of surgical therapy for facial basal-cell carcinoma (BCC) employing a multivariate analysis. METHODS: One hundred one patients who underwent ablative surgery for BCC of the face at the Department of Oral and Maxillofacial Surgery/ Plastic Surgery, University Hospital Jena, between April 2005 and January 2009, were analyzed. Patients' charts were screened for anamnestic features as well as management- and follow-up-related details. Standardized photographs were subjected to an esthetic evaluation. Logistic regression was used to identify factors associated with postsurgical wound healing disorders, recurrence, and esthetic impairment. RESULTS: Following surgical BCC treatment, age and tumor location in the area of the eyes, nose, lips, and ears were independent predictors of wound healing disorders. Tumor location in the area of the eyes, nose, lips, and ears, subtype and class were independent predictors of recurrence. Female gender and location in the area of the eyes, nose, lips, and ears were independent predictors of esthetic impairment. Micrographic surgery and distant reconstruction technique were management-related predictors of wound healing disorders and esthetic outcome, respectively. CONCLUSIONS: The identified negative predictors of treatment outcome should be included in the informed consent to objectify the patient's preoperative expectations. PMID- 20349094 TI - Effects of GDF5 overexpression on embryonic rat dopaminergic neurones in vitro and in vivo. AB - Transplantation of embryonic dopaminergic neurones has shown promise for the treatment of Parkinson's disease (PD), but this approach is limited by the poor survival of the transplanted cells. Exogenous dopaminergic neurotrophic factors such as growth/differentiation factor 5 (GDF5) have been found to enhance the survival of transplanted dopaminergic neurones. However, this approach is limited by the rapid degradation of such factors in vivo; thus, methods for long-term delivery of these factors are under investigation. The present study shows, using optimised lipid-mediated transfection procedures, that overexpression of GDF5 significantly improves the survival of dopaminergic neurones in cultures of embryonic day (E) 13 rat ventral mesencephalon (VM) and protects them against 6 hydroxydopamine (6-OHDA)-induced toxicity. In another experiment, E13 VM cells were transfected with GDF5 after 1 day in vitro (DIV), then transplanted into 6 OHDA-lesioned adult rat striata after 2 DIV. The survival of these E13 VM dopaminergic neurones after transfection and transplantation was as least as high as that of freshly dissected E14 VM dopaminergic neurones, demonstrating that transfection was not detrimental to these cells. Furthermore, GDF5-overexpressing E13 VM transplants significantly reduced amphetamine-induced rotational asymmetry in the lesioned rats. This study shows that lipid-mediated transfection in vitro prior to transplantation is a valid approach for the introduction of neurotrophic proteins such as GDF5, as well as lending further support to the potential use of GDF5 in neuroprotective therapy for PD. PMID- 20349097 TI - Hyperckemia after phenol intoxication. PMID- 20349098 TI - Evolutionary patterns in pearl oysters of the genus Pinctada (Bivalvia: Pteriidae). AB - Pearl oysters belonging to the genus Pinctada (Bivalvia: Pteriidae) are widely distributed between the Indo-Pacific and western Atlantic. The existence of both widely distributed and more restricted species makes this group a suitable model to study diversification patterns and prevailing modes of speciation. Phylogenies of eight out of the 11 currently recognised Pinctada species using mitochondrial (cox1) and nuclear (18S rRNA) data yielded two monophyletic groups that correspond to shell size and presence/absence of hinge teeth. Character trace of these morphological characters onto the molecular phylogeny revealed a strong correlation. Pinctada margaritifera appears polyphyletic with specimens from Mauritius grouping in a different clade from others of the French Polynesia and Japan. Hence, P. margaritifera might represent a species complex, and specimens from Mauritius could represent a different species. Regarding the putative species complex Pinctada fucata/Pinctada martensii/Pinctada radiata/Pinctada imbricata, our molecular analyses question the taxonomic validity of the morphological characters used to discriminate P. fucata and P. martensii that exhibited the lowest genetic divergence and are most likely conspecific as they clustered together. P. radiata and P. imbricata were recovered as monophyletic. The absence of overlapping distributions between sister lineages and the observed isolation by distance suggests that allopatry is the prevailing speciation mode in Pinctada. Bayesian dating analysis indicated a Miocene origin for the genus, which is consistent with the fossil record. The northward movement of the Australian plate throughout the Miocene played an important role in the diversification process within Pinctada. PMID- 20349099 TI - Microvascular decompression for treating hemifacial spasm: lessons learned from a prospective study of 1,174 operations. AB - The authors critically analyzed a large series of patients with hemifacial spasm (HFS) and who underwent microvascular decompression (MVD) under a prospective protocol. We describe several "lessons learned" that are required for achieving successful surgery and proper postoperative management. The purpose of this study is to report on our experience during the previous 10 years with this procedure and we also discuss various related topics. From April 1997 to June 2009, over 1,200 consecutive patients underwent MVD for HFS. Among them, 1,174 patients who underwent MVD for HFS with a minimum 1 year follow-up were enrolled in the study. The median follow-up period was 3.5 years (range, 1-9.3 years). Based on the operative and medical records, the intraoperative findings and the postoperative outcomes were obtained and then analyzed. At the 1-year follow-up examination, 1,105 (94.1%) patients of the total 1,174 patients exhibited a "cured" state, and 69 (5.9%) patients had residual spasms. In all the patients, the major postoperative complications included transient hearing loss in 31 (2.6%), permanent hearing loss in 13 (1.1%), transient facial weakness in 86 (7.3%), permanent facial weakness in 9 (0.7%), cerebrospinal fluid leak in three (0.25%) and cerebellar infarction or hemorrhage in two (0.17%). There were no operative deaths. Microvascular decompression is a very effective, safe modality of treatment for hemifacial spasm. MVD is not sophisticated surgery, but having a basic understanding of the surgical procedures is required to achieve successful surgery. PMID- 20349100 TI - D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases. AB - This study sought to describe and evaluate any relationship between D-dimer values and progressive hemorrhagic injury (PHI) after traumatic brain injury (TBI). In patients with TBI, plasma D-dimer was measured while a computed tomography (CT) scan was conducted as soon as the patient was admitted to the emergency department. A series of other clinical and laboratory parameters were also measured and recorded. A logistic multiple regression analysis was used to identify risk factors for PHI. A cohort of 194 patients with TBI was evaluated in this clinical study. Eighty-one (41.8%) patients suffered PHI as determined by a second CT scan. The plasma D-dimer level was higher in patients who demonstrated PHI compared with those who did not (P < 0.001. Using a receiver-operator characteristic curve to predict the possibility by measuring the D-dimer level, a value of 5.00 mg/L was considered the cutoff point, with a sensitivity of 72.8% and a specificity of 78.8%. Eight-four patients had D-dimer levels higher than the cut point value (5.0 mg/L); PHI was seen in 71.4% of these patients and in 19.1% of the other patients (P < 0.01). Factors with P < 0.2 on bivariate analysis were included in a stepwise logistic regression analysis to identify independent risk factors for TBI coagulopathy. Logistic regression analysis showed that the D-dimer value was a predictor of PHI, and the odds ratio (OR) was 1.341 with per milligram per liter (P = 0.020). The stepwise logistic regression also identified that time from injury to the first CT shorter than 2 h (OR = 2.118, P = 0.047), PLT counts lesser than 100 x 109/L (OR = 7.853, P = 0.018), and Fg lower than 2.0 g/L (OR = 3.001, P = 0.012) were risk factors for the development of PHI. When D-dimer values were dichotomized at 5 mg/L, time from injury to the first CT scan was no longer a risk factor statistically while the OR value of D-dimer to the occurrence of PHI elevated to 11.850(P < 0.001). The level of plasma D-dimer after TBI can be a useful prognostic factor for PHI and should be considered in the clinical management of patients in combination with neuroimaging and other data. PMID- 20349101 TI - Evaluation of the clinical cutoff level of serum (1 --> 3)-beta-D-glucan in patients with connective tissue diseases complicated by deep fungal infections. AB - Serum (1 --> 3)-beta-D-glucan levels and clinical findings were evaluated in 229 inpatients with connective tissue diseases (CTDs) during the period between June and October 2004. The mean serum (1 --> 3)-beta-D-glucan level was 129.7 +/- 207.6 pg/mL in patients with a definitive diagnosis of fungal infections and 10.5 +/- 8.6 pg/mL in patients without fungal infections. Analysis of the diagnostic sensitivity/specificity for various (1 --> 3)-beta-D-glucan cutoff levels gave the best results for a cutoff level of 15 pg/mL, with a sensitivity of 92.3% and specificity of 81.3%. This level was therefore determined to be the optimal cutoff in patients with CTDs. PMID- 20349096 TI - RNA processing pathways in amyotrophic lateral sclerosis. AB - RNA processing is a tightly regulated, highly complex pathway which includes RNA transcription, pre-mRNA splicing, editing, transportation, translation, and degradation of RNA. Over the past few years, several RNA processing genes have been shown to be mutated or genetically associated with amyotrophic lateral sclerosis (ALS), including the RNA-binding proteins TDP-43 and FUS/TLS. These findings suggest that RNA processing may represent a common pathogenic mechanism involved in development of ALS. In this review, we will discuss six ALS-related, RNA processing genes including their discovery, function, and commonalities. PMID- 20349102 TI - Risk and uncertainty in health investment. AB - Extending the Grossman (J Polit Econ 80:223-255, 1972) model of health capital into a stochastic one, we analyze how the presence of Knightian uncertainty about the efficacy of health care affects the optimal health investment behavior of individuals. Using Gilboa and Schmeidler's (J Math Econ 18:141-153, 1989) model of max/min expected utility (MMEU) with multiple priors, we show that an agent retains the initial level of health capital if the price of health care lies within a certain range. We also show that the no-investment range expands as the degree of Knightian uncertainty rises. PMID- 20349104 TI - Lactococcus lactis catheter-related bacteremia in an infant. PMID- 20349105 TI - Recent diarrhea is associated with elevated salivary IgG responses to Cryptosporidium in residents of an eastern Massachusetts community. AB - BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults. MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a time-resolved fluorometric immunoassay. Log-transformed assay results were regressed on age using penalized B-splines to account for the strong age-dependence of antibody reactions. Positive responses were defined as fluorescence values above the upper 99% prediction limit. RESULTS: Forty-seven (13.5%) individuals had diarrhea without concurrent respiratory symptoms during the 3-month-long follow-up; eight of them had these symptoms during the month prior to saliva sampling. Two individuals had positive IgG responses: an adult who had diarrhea during the prior month and a child who had episodes of diarrhea during each survey month (Fisher's exact test for an association between diarrhea and IgG response: p = 0.0005 for symptoms during the prior month and p = 0.02 for symptoms during the entire follow-up period). The child also had a positive IgA response, along with two asymptomatic individuals (an association between diarrhea and IgA was not significant). CONCLUSION: These results suggest that the salivary IgG specific to Cryptosporidium antigens warrants further evaluation as a potential indicator of recent infections. PMID- 20349106 TI - Hospital-acquired pneumonia and bacteremia caused by Legionella pneumophila in an immunocompromised patient. AB - The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully treated with ceftazidime and clindamycin initially, followed by ciprofloxacin for 14 days. The blood isolate was further confirmed by 16S rDNA sequence analysis. PMID- 20349108 TI - Butanol production by Clostridium acetobutylicum in a continuous packed bed reactor. AB - In this study, we report on a butanol production process by immobilized Clostridium acetobutylicum in a continuous packed bed reactor (PBR) using Tygon rings as a carrier. The medium was a solution of lactose (15-30 g/L) and yeast extract (3 g/L) to emulate the cheese whey, an abundant lactose-rich wastewater. The reactor was operated under controlled conditions with respect to the pH and to the dilution rate. The pH and the dilution rate ranged between 4 and 5, the dilution rate between 0.54 and 2.4 h(-1) (2.5 times the maximum specific growth rate assessed for suspended cells). The optimal performance of the reactor was recorded at a dilution rate of 0.97 h(-1): the butanol productivity was 4.4 g/Lh and the selectivity of solvent in butanol was 88%(w). PMID- 20349107 TI - The selective COX-2 inhibitor Etoricoxib reduces acute inflammatory markers in a model of neurogenic laryngitis but loses its efficacy with prolonged treatment. AB - OBJECTIVE: A randomised experimental study was used to evaluate the therapeutic effect of a selective cyclooxygenase-2 (COX-2) inhibitor in neurogenic laryngitis. MATERIALS AND METHODS: Male Wistar Han rats were subjected to the nasogastric intubation model (NGI) of laryngitis for 1 and 2 weeks. The NGI animals were divided into three groups: (1) treated with COX-2 inhibitor Etoricoxib, (2) vehicle and (3) non-intubated animals. A fourth group of animals was submitted to NGI only. Laryngeal sections were immunostained for substance P (SP) and calcitonin gene-related peptide (CGRP) fibre-immunoreactivity (IR) and quantification of COX-2 positive cells through stereological analysis. The expression of COX-2, interleukins IL-1beta, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha) was determined by quantitative real time QRT-PCR. TREATMENT: Etoricoxib (6 mg/kg/day) was prepared in 0.9% sterile saline with 5% glucose (vehicle) and administered daily during 1 or 2 weeks. RESULTS: Treatment for 1 week with Etoricoxib attenuated the CGRP-IR fibre depletion, the COX-2-IR increased cell number and the TNF-alpha and COX-2 mRNA increased levels induced by NGI. Two weeks of treatment had no beneficial effect. CONCLUSIONS: Etoricoxib is effective in neurogenic laryngitis for limited periods of administration, indicating that selective COX-2 inhibitors should be evaluated in the future. PMID- 20349110 TI - Novel Escherichia coli hybrids with enhanced butanol tolerance. AB - Hybrids between Escherichia coli and Lactobacillus brevis were generated via protoplast fusion. Growth kinetics of five hybrid strains and E. coli were used to evaluate the butanol tolerance of the novel strains under different conditions. The hybrid strains tolerated up to 2% (v/v) butanol compared to the 1% (v/v) maximum for E. coli. The growth inhibitory effects of butanol were also significantly less in several of the hybrids compared to E. coli. These results demonstrate the potential use of protoplast fusion to generate butanol-tolerant strains. PMID- 20349111 TI - Antitumor activity of methylan polysaccharide derivatives. AB - Methylan polysaccharide derivatives were prepared by dialkylaminoalkylation and reductive amination followed by quaternization. Their antitumor activity was investigated and a relationship between structure and activity is suggested. For quaternized DEAE-methylan at only 75 mug ml(-1), tumor cell proliferation was suppressed by 58-84% in three cell lines tested in the order Colo < Hela < HepG2. PMID- 20349109 TI - Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks. AB - Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies. PMID- 20349112 TI - Growth factor production from fibrin-encapsulated human keratinocytes. AB - Fibrin has been used extensively in cell encapsulation because it has important biological properties. Keratinocyte encapsulation in fibrin is a widely used technique in skin tissue engineering. The production of growth factors (EGF, TGF beta1 and PDGF-BB) was evaluated when keratinocytes are encapsulated in fibrin. Secretions of TGF-beta1 and PDGF-BB increased more than five times compared to monolayer cultures. Encapsulated cells secreted about 80% active form of TGF beta1 (monolayer cells only secreted inactive form). An enhanced secretion of TGF beta1 and PDGF-BB was found in encapsulated cells, showing that fibrin capsules are favourable for the production of these growth factors. PMID- 20349113 TI - Glutathione-mediated response to acid stress in the probiotic bacterium, Lactobacillus salivarius. AB - Lactobacillus salivarius, a probiotic bacterium, encounters acidic conditions in its passage through the gastrointestinal tract of human and animal hosts. We studied the effect of a rapid downshift in extracellular pH from 6.5 to 4 on cell growth. The maximum growth rate was higher in low pH medium with glutathione supplementation than without. Cells developed a GSH-mediated acid-tolerance response and, when grown with 0.5 mM GSH, reached a higher final density than with other conditions. These findings suggest that the increased growth rate is caused by uptake of GSH which acts as a nutrient source as well as having protective functions, allowing for continued growth. PMID- 20349114 TI - Tautomers and reference 3D-structures: the orphans of in silico drug design. AB - The importance of calculating not only the correct tautomer, but also the correct protonation state and conformation in 3D modeling applications is emphasized. Above all, identifying and characterizing the most stable form of a ligand under physiological conditions is seen to be the key to successful 3D modeling. Modeling strategies that make use of the performance of modern hardware can employ physically more appropriate models than most currently in use and still be easily applicable to large numbers of compounds. Because the performance of quantitative structure-property relationships is likely to be limited by the available training and validation data, we must either find new sources of such data or resort to explicit modeling, which can partly be parameterized using definitive ab initio calculations for reference data such as gas-phase proton affinities. PMID- 20349115 TI - Natural variation explains most transcriptomic changes among maize plants of MON810 and comparable non-GM varieties subjected to two N-fertilization farming practices. AB - The introduction of genetically modified organisms (GMO) in many countries follows strict regulations to ensure that only safety-tested products are marketed. Over the last few years, targeted approaches have been complemented by profiling methods to assess possible unintended effects of transformation. Here we used a commercial (Affymertix) microarray platform (i.e. allowing assessing the expression of approximately 1/3 of the genes of maize) to evaluate transcriptional differences between commercial MON810 GM maize and non-transgenic crops in real agricultural conditions, in a region where about 70% of the maize grown was MON810. To consider natural variation in gene expression in relation to biotech plants we took two common MON810/non-GM variety pairs as examples, and two farming practices (conventional and low-nitrogen fertilization). MON810 and comparable non-GM varieties grown in the field have very low numbers of sequences with differential expression, and their identity differs among varieties. Furthermore, we show that the differences between a given MON810 variety and the non-GM counterpart do not appear to depend to any major extent on the assayed cultural conditions, even though these differences may slightly vary between the conditions. In our study, natural variation explained most of the variability in gene expression among the samples. Up to 37.4% was dependent upon the variety (obtained by conventional breeding) and 31.9% a result of the fertilization treatment. In contrast, the MON810 GM character had a very minor effect (9.7%) on gene expression in the analyzed varieties and conditions, even though similar cryIA(b) expression levels were detected in the two MON810 varieties and nitrogen treatments. This indicates that transcriptional differences of conventionally bred varieties and under different environmental conditions should be taken into account in safety assessment studies of GM plants. PMID- 20349116 TI - Selection by socioeconomic factors into the Danish National Birth Cohort. AB - BACKGROUND: Low participation at recruitment to the Danish National Birth Cohort (DNBC) has raised concern about non-participation bias. Objective To study the socioeconomic pattern of participation to the DNBC. METHODS: Independently of the DNBC, we identified the DNBC source population in two geographical areas of Denmark by means of local birth registers with full coverage. Socioeconomic information came from national registers, and the source population consisted of 48,560 births including 15,290 participating women. For every socioeconomic characteristic, we estimated the prevalence ratio [prevalence (participants)/prevalence (source population)] which corresponds to the relative representation of the group (presented in percentages with 95% confidence intervals). RESULTS: The overall participation rate was 31%. Women outside the work force or with no further education than compulsory school were underrepresented in the DNBC by 62% (59%; 64%) and 43% (41%; 45%), respectively. Also, women were underrepresented by 18% (13%; 23%) if they were unemployed, by 22% (20%; 24%) if they were in the lowest income group, 38% (35%; 40%) if they received a high proportion of social benefits, and 28% (24%; 31%) if they were singles. Particularly women with low resources according to two socioeconomic factors were strongly underrepresented, typically by 50-67%. CONCLUSION: Groups with low socioeconomic resources in terms of education, occupation, income and civil status are underrepresented in the DNBC compared to the background population. These discrepancies must be taken into account when results from the DNBC and other cohorts of pregnant women are interpreted-especially when descriptive results are presented. PMID- 20349117 TI - Regucalcin and metabolic disorders: osteoporosis and hyperlipidemia are induced in regucalcin transgenic rats. AB - Regucalcin transgenic (TG) rat has been generated to determine the role in metabolic disorders. Regucalcin homozygote male and female rats induce a prominent increase in regucalcin protein in the various tissues. Bone loss has been found to induce in regucalcin TG rats with growing (5 weeks old) and aging (50 weeks old). Osteoclastogenesis has been shown to stimulate in culture with the bone marrow cells obtained from regucalcin TG rats. Exogenous regucalcin stimulates osteoclastogenesis in mouse marrow culture in vitro. Regucalcin has a suppressive effect on the differentiation and mineralization in osteoblastic MC3T3-E1 cells in vitro. The mechanism by which regucalcin TG rat induces bone loss may result from the enhancement of osteoclastic bone resorption and the suppression of osteoblastic bone formation. Moreover, regucalcin TG rat has been found to induce hyperlipidemia with increasing age (14-50 weeks); serum triglyceride, high-density lipoprotein (HDL)-cholesterol, free fatty acid, albumin and calcium concentrations are markedly increased in regucalcin TG male and female rats with increasing age. The decrease in lipid and glycogen contents in liver tissues is induced in regucalcin TG rats. The gene expression of leptin and adiponectin is suppressed in the TG rats. Overexpression of regucalcin has been shown to enhance glucose utilization and lipid production in the cloned rat hepatoma H4-II-E cells in vitro, and insulin resistance is seen in the cells. The expression of glucose transporter 2 mRNA is increased in the transfectants, while it has been shown to suppress insulin receptor and phosphatidylinositol 3-kinase mRNA expressions that are involved in insulin signaling. This review proposes that regucalcin relates in osteoporosis and hyperlipidemia, and that the regucalcin TG rat model may be useful in determining the pathophysiologic state and the development of therapeutic tool for osteoporosis and hyperlipidemia. PMID- 20349118 TI - Bioinformatic and biochemical studies point to AAGR-1 as the ortholog of human acid alpha-glucosidase in Caenorhabditis elegans. AB - Human acid alpha-glucosidase (GAA, EC 3.2.1.20) is a lysosomal enzyme that belongs to the glycoside hydrolase family 31 (GH31) and catalyses the hydrolysis of alpha-1,4- and alpha-1,6-glucosidic linkages at acid pH. Hereditary deficiency of GAA results in lysosomal glycogen storage disease type II (GSDII, Pompe disease). The aim of this study was to assess GH31 proteins in Caenorhabditis elegans (C. elegans) to identify the ortholog of human GAA. Bioinformatic searches for GAA ortholog in C. elegans genome revealed four acid alpha glucosidase-related (aagr-1-4) genes. Multiple sequence alignment of AAGRs with other GH31 proteins demonstrated their evolutionary conservation. Phylogenetic analyses suggested clustering of AAGR-1 and -2 with acid-active and AAGR-3 and -4 with neutral-active GH31 enzymes. In order to prove the AAGRs' predicted alpha glucosidase activity, we performed RNA interference of all four aagr genes. The impact on the alpha-glucosidase activity was evaluated at pH 4.0 (acid) and pH 6.5 (neutral), with or without the inhibitor acarbose. AAGR-1 and -2 expressed acidic alpha-glucosidase activity; on the contrary, AAGR-3 not -4 represented the predominant neutral alpha-glucosidase activity in C. elegans. Similar results were obtained in each of aagr-1 and -4 deletion mutants. Moreover, based on our structural models of AAGRs and these biochemical experiments, we hypothesize that the enzymatic sensitivity of AAGR-2 and human maltase-glucoamylase to the inhibitor acarbose is associated with a tyrosine residue in the GH31 active site, whereas acarbose resistance of AAGR-1 and human GAA is associated with the corresponding tryptophane in the active site. Acid-active AAGR-1 may thus represent the ortholog of human GAA in C. elegans. PMID- 20349119 TI - Identification, characterization, and expression of a unique secretory lipase from the human pathogen Leishmania donovani. AB - Lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. Potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. Using a molecular approach, we identified and characterized the structure of an LdLip3-lipase gene from the primitive trypanosomatid pathogen of humans, Leishmania donovani. The LdLip3 encodes a approximately 33 kDa protein, with a well-conserved substrate-binding and catalytic domains characteristic of members of the serine lipase-protein family. Further, we showed that LdLip3 mRNA is constitutively expressed by both the insect vector (i.e., promastigote) and mammalian (i.e., amastigote) life cycle developmental forms of this protozoan parasite. Moreover, a homologous episomal expression system was used to express an HA epitope-tagged LdLip3 chimeric construct (LdLip3::HA) in these parasites. Expression of the LdLip3 chimera was verified in these transfectants by Western blots and indirect immuno fluorescence analyses. Results of coupled immuno-affinity purification and enzyme activity experiments demonstrated that the LdLip3::HA chimeric protein was secreted/released by transfected L. donovani parasites and that it possessed functional lipase enzyme activity. Taken together these observations suggest that this novel secretory lipase might play essential role(s) in the survival, growth, and development of this important group of human pathogens. PMID- 20349120 TI - Building a tool to identify risk for Lynch syndrome among individuals presenting for screening colonoscopy. AB - The goal of this work was to build and pilot-test a user-friendly Lynch syndrome risk assessment tool among individuals presenting for routine screening colonoscopy. Participants included adults presenting to a private practice-based, open-access endoscopy unit. Working with health literacy experts and gastroenterologists, and based on established criteria, we developed a simplified tool to assess Lynch syndrome risk, pre-procedure. A pilot-test of the tool assessed its: 1) clinical utility; 2) patient-reported usability; and 3) feasibility. The tool, in paper format, was written at a 9th grade reading level and included instructions for use followed by seven Lynch syndrome risk-related questions, structured such that one "Yes" response signified potential risk. A pilot-test of the tool among 334 patients revealed that 29 met criteria for Lynch syndrome risk. Of these, following telephone review of their responses, risk was confirmed in 9 patients (3% of total). The tool was reported as easy-to-use and was seen as feasible for use. Limitations include: 1) the need for infrastructure to distribute and collect the tool and 2) the availability of knowledgeable staff to review tool responses, confirm risk, and facilitate appropriate referral for genetic counseling. These data suggest that the tool affects assessment of Lynch syndrome risk among the routine colon cancer screening population. PMID- 20349121 TI - Topological analysis of ATAD3A insertion in purified human mitochondria. AB - ATAD3 is a mitochondrial inner membrane-associated protein that has been predicted to be an ATPase but from which no associated function is known. The topology of ATAD3 in mitochondrial membranes is not clear and subject to controversy. A direct interaction of the N-terminal domain (amino-acids 44-247) with the mtDNA has been described, but the same domain has been reported to be sensitive to limited proteolysis in purified mitochondria. Furthermore, ATAD3 has been found in a large purified nucleoid complex but could not be cross-linked to the nucleoid. To resolve these discrepancies we used two immunological approaches to test whether the N-terminal (amino-acids 40-53) and the C-terminal (amino acids 572-586) regions of ATAD3 are accessible from the cytosol. Using N-terminal and C-terminal specific anti-peptide antibodies, we carried out back-titration ELISA measurements and immuno-fluorescence analysis on freshly purified human mitochondria. Both approaches showed that the N-terminal region of ATAD3A is accessible to antibodies in purified mitochondria. The N-terminal region of ATAD3A is thus probably in the cytoplasm or in an accessible intermembrane space. On the contrary, the C-terminal region is not accessible to the antibody and is probably located within the matrix. These results demonstrate both that the N terminal part of ATAD3A is outside the inner membrane and that the C-terminal part is inside the matrix. PMID- 20349122 TI - Innate immune detection of bacterial virulence factors via the NLRC4 inflammasome. AB - INTRODUCTION: Cytokine production by innate immune cells is initiated by signaling downstream of pattern recognition receptors, including Toll-like receptors. DISCUSSION: A subset of cytokines, including IL-1beta and IL-18, require post-translational proteolysis before secretion, which provides a second mechanism of regulation. This proteolysis is dependent upon caspase 1, which is activated by Nod-like receptor (NLR) signaling. NLRC4 (previously named Ipaf) activates caspase 1 in response to bacterial virulence factors including type III and IV secretion systems (T3SS and T4SS). NLRC4 recognizes T3SS/T4SS in two ways: indirectly by detecting flagellin, and directly by detecting the T3SS rod protein. Both flagellin and rod protein are unintentionally delivered to the mammalian cytosol by the bacterium through the T3SS. PMID- 20349124 TI - Morphological and biochemical changes during formocresol induced cell death in murine peritoneal macrophages: apoptotic and necrotic features. AB - The present study was conducted to investigate the role of Formocresol (FC) induced apoptosis and necrotic cell death in murine peritoneal macrophages (pMo). Macrophages were cultured with 1:100 FC for 2 to 24 h. The viability (trypan blue assay), cell morphology (scanning electronic microscope), and apoptotic and necrotic indexes (light and fluorescent microscopy) were determined at different scheduled times. Simultaneously, the expressions of proteins related to stress, survival, and cell death were measured by western blotting. FC-exposed macrophages exhibited maximal apoptosis from 2 to 6 h, coincident with Bax overexpression (P < 0.001). Additionally, Bcl-x(L) showed maximal expression between 12 and 24 h suggesting its survival effect in pMo. The lowest pMo viability and the increment of the necrotic rate from 4 to 12 h were observed in accordance to Fas and Hsp60 overexpressions. In summary, all the experimental data suggest that two different pathways emerge in pMo exposed to FC, one leading Bax-dependent apoptosis (2-6 h) and the other one favoring necrosis (4-18 h), related to Fas-receptor and Hsp60 stress signal. PMID- 20349123 TI - TL1A selectively enhances IL-12/IL-18-induced NK cell cytotoxicity against NK resistant tumor targets. AB - INTRODUCTION: TL1A (TNFSF15) augments IFN-gamma production by IL-12/IL-18 responsive human T cells. Its ligand, death domain receptor 3 (DR3), is induced by activation on T and NK cells. Although IL-12/IL-18 induces DR3 expression on most NK cells, addition of TL1A minimally increases IFN-gamma production. METHODS: (51)Chromium release and flow cytometric analysis were used to determine whether the TL1A-DR3 pathway is implicated in tumor cell lysis. Our aim was to determine whether the TL1A-DR3 pathway is implicated in tumor cell lysis. RESULTS: TL1A had no additional effect on IL-12/IL-18-induced cytotoxicity against an NK-susceptible tumor (K562); however, it promoted cytotoxicity against NK-resistant targets susceptible to lysis only by activated NK cells. DISCUSSION: With IL-12/IL-18 activation, TL1A increased CD107a expression on NK cells which led to enhanced lysis of Daudi by PBMC and purified NK cells. To a lesser degree, TL1A increased lysis of colorectal adenocarcinoma epithelial derived lines (WiDr and SW837) by IL-12/IL-18-activated cells. CONCLUSION: TL1A increased cytotoxicity of IL-12/IL-18-activated NK cells against target cells dependent on NK activation for lysis and could function in vivo as a key co-activator of NK cytotoxicity. PMID- 20349125 TI - Cancer risk in relationship to different indicators of adult socioeconomic position in Turin, Italy. AB - OBJECTIVE: To determine the magnitude of social inequalities in cancer incidence according to different socioeconomic indicators and to assess the independent role of each indicator. METHODS: Data from the Turin Longitudinal Study and the Piedmont Cancer Registry (1985-1999) were used to analyse the relationship of cancer incidence with three dimensions of individual socioeconomic position (education, occupation, and material living conditions) and with an area-based deprivation index. Multivariate Poisson regression models were used to estimate both relative risks and relative indexes of inequality (RIIs). RESULTS: Results showed an independent role of all the socioeconomic indicators. The overall gradients of inequalities, expressed by the RIIs for total cancer incidence, varied from 9 to 26% among men; among women, we estimated a 22% protection at the bottom of the educational hierarchy, and a 12% gradient for decreasing ease of living conditions. For most cancer sites, socioeconomic position in early adult life was as important as later socioeconomic position, while the area-based deprivation index played only an additional role. CONCLUSIONS: Different socioeconomic indicators pinpoint to a series of specific risk factors that are related to specific phases of the life course. Individual level data, rather than ecological data, is preferred to accurately monitor social inequalities in cancer risk. PMID- 20349127 TI - The p21 Ser31Arg polymorphism and breast cancer risk: a meta-analysis involving 51,236 subjects. AB - Published data on the association between p21 Ser31Arg polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between the p21 Ser31Arg polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Ser/Arg vs. Ser/Ser, Arg/Arg vs. Ser/Ser), dominant model (Arg/Arg + Ser/Arg vs. Ser/Ser), and recessive model (Arg/Arg vs. Ser/Arg + Ser/Ser). A total of 21 studies including 22,109 cases and 29,127 controls were involved in this meta analysis. Overall, no significant associations were found between p21 Ser31Arg polymorphism and breast cancer risk when all studies pooled into the meta analysis. In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (Arg/Arg vs. Ser/Ser: OR 1.496, 95% CI 1.164-1.924; and recessive model: OR 1.492, 95% CI 1.161-1.919). When stratified by study design, statistically significantly elevated risk was found for population-based studies (Ser/Arg vs. Ser/Ser: OR 1.085, 95% CI 1.019-1.156). In conclusion, this meta analysis suggests that the p21 Ser31Arg polymorphism may be associated with breast cancer development in Caucasian. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding. PMID- 20349126 TI - Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, including binge drinking: a population-based study. AB - Alcohol consumption is postulated to be a risk factor for pancreatic cancer (PCA), but clarification of degree of risk related to consumption characteristics is lacking. We examined the association between alcohol consumption and PCA in a population-based case-control study (532 cases, 1,701 controls) in the San Francisco Bay Area. Population-based controls were frequency-matched by sex, age within 5-year categories and county of residence to cases identified by the cancer registry's rapid case ascertainment. Detailed alcohol consumption data, including binge drinking (>or=5 drinks/day), were collected during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using adjusted unconditional logistic regression. Depending on dose, duration, and pattern of drinking, ORs were increased 1.5- to 6-fold among men but not women. In men, ORs increased with increasing overall alcohol consumption (22-35 drinks/week OR = 2.2, 95% CI = 1.1-4.0; >or=35 drinks/week OR = 2.6, 95% CI = 1.3 5.1, p-trend = 0.04). Most notable were effects with a history of binge drinking (OR = 3.5, 95% CI = 1.6-7.5) including increased number of drinks per day (p trend = 0.002), and increased years of binge drinking (p-trend = 0.0006). In fully adjusted models that included smoking and other confounders, ORs for binge drinking in men were somewhat higher than in age-adjusted models. Results from our detailed analyses provide support for heavy alcohol consumption (including binge drinking) as a risk factor for PCA in men. PMID- 20349128 TI - Genetic influences on mammographic density in Korean twin and family: the Healthy Twin study. AB - Higher mammographic density is a strong risk factor for breast cancer. This study was conducted to determine the role of genetic factors on mammographic density measurements in Korean women. Study subjects were 730 women (122 monozygotic (MZ) twin pairs, 28 dizygotic (DZ) twin pairs, and 430 first degree relatives) from the Healthy Twin study. Mammographic density was measured using a computer assisted method. Pairwise correlations of residual variance of each component of mammographic density were calculated within each pair of twins and family members. Quantitative genetic analysis was completed using SOLAR. Age and measured covariates accounted for 50% of the variation in dense area, 70% of non dense area, and 67% of percent dense area. Fully adjusted heritability coefficients for dense area, non-dense area, and percent dense area were 0.76 (SE = 0.04), 0.69 (SE = 0.04) and 0.68 (SE = 0.04), respectively. Pairwise correlation coefficients of the adjusted residual variance of the mammographic density measures within MZ pairs and within DZ and sibling pairs combined were, respectively, 0.70 and 0.28 for dense area, 0.52 and 0.31 for non-dense area, and 0.58 and 0.24 for percent dense area. Covariance between dense and non-dense area had a significant genetic basis (correlation coefficient = -0.25, SE = 0.06). The same high heritability of mammographic density in Korean women as found in Western women supports a significant role of genetic determinants in breast cancer development. Genes that are responsible for familial correlation in mammographic density and have opposite effects on dense and non-dense mammographic areas need to be elucidated. PMID- 20349129 TI - Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors. AB - Breast cancer progression depends upon the elaboration of a vasculature sufficient for the nourishment of the developing tumor. Breast tumor cells frequently contain a mutant form of p53 (mtp53), a protein which promotes their survival. The aim of this study was to determine whether combination therapy targeting mtp53 and anionic phospholipids (AP) on tumor blood vessels might be an effective therapeutic strategy for suppressing advanced breast cancer. We examined the therapeutic effects, singly, or in combination, of p53 reactivation and induction of massive apoptosis (PRIMA-1), which reactivates mtp53 and induces tumor cell apoptosis, and 2aG4, a monoclonal antibody that disrupts tumor vasculature by targeting AP on the surface of tumor endothelial cells and causes antibody-dependent destruction of tumor blood vessels, leading to ischemia and tumor cell death. Xenografts from two tumor cell lines containing mtp53, BT-474 and HCC-1428, were grown in nude mice to provide models of advanced breast tumors. After treatment with PRIMA-1 and/or 2aG4, regressing tumors were analyzed for vascular endothelial growth factor (VEGF) expression, blood vessel loss, and apoptotic markers. Individual drug treatment led to partial suppression of breast cancer progression. In contrast, combined treatment with PRIMA-1 and 2aG4 was extremely effective in suppressing tumor growth in both models and completely eradicated approximately 30% of tumors in the BT-474 model. Importantly, no toxic effects were observed in any treatment group. Mechanistic studies determined that PRIMA-1 reactivated mtp53 and also exposed AP on the surface of tumor cells as determined by enhanced 2aG4 binding. Combination treatment led to significant induction of tumor cell apoptosis, loss of VEGF expression, as well as destruction of tumor blood vessels. Furthermore, combination treatment severely disrupted tumor blood vessel perfusion in both tumor models. The observed in vitro PRIMA-1-induced exposure of tumor epithelial cell AP might provide a target for 2aG4 and contribute to the increased effectiveness of such combination therapy in vivo. We conclude that the combined targeting of mtp53 and the tumor vasculature is a novel effective strategy for combating advanced breast tumors. PMID- 20349130 TI - Transforming growth factorbeta1 L10P variant plays an active role on the breast cancer susceptibility in Caucasian: evidence from 10,392 cases and 11,697 controls. AB - In view of the essential role of transforming growth factorbeta1 (TGFB1) on both inhibiting the development of early benign breast tumors as well as promoting tumor invasion, the association of TGFB1 L10P polymorphism and breast cancer risk has been widely reported, but results of previous studies were somewhat contradictory and underpowered. To overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta analysis towards the association between TGFB1 L10P polymorphism and breast cancer. Through retrieving MEDLINE, PubMed, Embase, and Web of Science, a total of 16 studies with 10,392 cases and 11,697 controls were identified. The results showed that significant association was found in the recessive genetic model for Caucasian (OR = 1.152, 95% CI = 1.020-1.301). However, we did not find any associations in additive genetic model (PP vs. LL for total: OR = 1.026, 95% CI = 0.940-1.121), allele contrast (L vs. P for total: OR = 1.004, 95% CI = 0.966 1.044), and dominant genetic model (PP + LP vs. LL for total: OR = 1.001, 95% CI = 0.946-1.061). Conclusively, this meta-analysis strongly suggests that TGFB1 L10P polymorphism may play a low penetrance role in breast cancer susceptibility in Caucasian. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis. PMID- 20349131 TI - Head circumference in the clinical detection of PTEN hamartoma tumor syndrome in a clinic population at high-risk of breast cancer. AB - PTEN Hamartoma Tumor Syndrome (PHTS) is often recognized by the presence of macrocephaly and associated mucocutaneous features, and is notable for a profound predisposition to breast and thyroid cancers. Head circumference (HC) is rarely measured when evaluating women at high risk for breast cancer, but may offer insight into characterizing cancer risk. Patients enrolled in the University of Michigan Cancer Genetics registry for breast cancer evaluation were analyzed for personal and family history of cancer and features of PHTS. This group of women was compared to all women who had undergone PTEN testing and whether or not they met clinical criteria for PHTS. Among the 164 women referred for breast cancer risk evaluation, a statistically significant difference in mean HC was found between women who did (57.3 cm) and did not (55.4 cm) meet clinical criteria for PHTS with both values below the established threshold for macrocephaly (58 cm). The sensitivity and specificity of macrocephaly for the presence of a PTEN mutation were 100 and 53%, respectively, among the 28 women tested. The positive predictive value was 14%. PTEN mutation positive and PTEN mutation negative women were not well differentiated by PHTS clinical criteria (P = 0.2348). The high sensitivity of HC suggests that this simple measure can improve the detection of unrecognized patients with PHTS. Measuring HC is a useful clinical feature, but is insufficient as a singular screening tool for PHTS. Even in a high risk population, the PPV of this test is low. Diagnosis of this important genetic syndrome still relies heavily on detailed history and full physical exam. PMID- 20349132 TI - Cadmium accumulation, metallothionein and glutathione levels, and histopathological changes in the kidneys and liver of magpie (Pica pica) from a zinc smelter area. AB - The objective of this study was to examine a relationship between cadmium (Cd) accumulation and histopathological changes in the kidneys and liver of magpies (Pica pica) from a zinc smelter area. The concentrations of metallothionein (MT) and glutathione (GSH) that are linked to a protective effect against Cd toxicity were also determined. There was a positive correlation between the concentration of Cd (2.2-17.9 microg/g) and histopathological changes (interstitial inflammation and tubular cell degeneration) in the kidneys (R (s) = 0.87, P = 0.0000). The renal Cd also positively correlated with apoptosis (R (s) = 0.72, P = 0.0005) but the metal did not affect lipid peroxidation. Notably, the average concentration of Cd in the kidneys exceeded MT capacity by about 7 microg/g which is thought to produce renal injury. Importantly, GSH level in the kidneys of magpies from the polluted area dropped to 38% of that observed in the reference birds, probably potentiating Cd toxicity. On the contrary, the liver accumulation of Cd was relatively small (0.88-3.38 microg/g), the hepatic MT capacity exceeded the total concentration of Cd and no association between the hepatic Cd and histopathology was found despite the fact that GSH level was only half that observed in the reference birds. The data suggest that Cd intoxication may be responsible for histopathological changes occurring in the kidneys of free ranging magpies and that the pathology may be associated with inappropriate amount of renal MT and GSH. PMID- 20349133 TI - The influence of seasonality on biomarker responses in Mytilus edulis. AB - The utility of some biomarkers in environmental monitoring may be limited due to the lack of knowledge that exists on how they respond to extrinsic abiotic and intrinsic biotic factors. During the present study we investigated the seasonal responses of three biomarkers, Neutral Red Retention, clearance/filtration rate and heart rate in the common blue mussel Mytilus edulis located in the Exe Estuary, UK during September 2006-September 2007. During the current study, a significant decrease in feeding rate was observed in mussels during June, July and August 2007, coinciding with the period following spawning when the mussels lay down nutrient reserves. Heart rate also increased between April and September 2007 and corresponded with times when mussels were spawning and laying down nutrient reserves. By integrating the individual biomarker responses into a Biomarker Response Index (BRI) we were able to identify times of the year when environmental impact was highest and hence when the timing of monitoring programmes using biomarkers should be carried out. For many years the lack of knowledge of normal physiological ranges of biomarkers has impeded their applied use, however by integrating biomarker responses into the BRI and creating an index of health, we have shown that we can limit the natural variability of individual responses; and thus we are better able to make informed judgements on the overall health status of these populations of mussels. PMID- 20349134 TI - CORAL: QSPR models for solubility of [C60] and [C70] fullerene derivatives. AB - Quantitative structure-property relationships (QSPRs) between the molecular structure of [C(60)] and [C(70)] fullerene derivatives and their solubility in chlorobenzene (mg/mL) have been established by means of CORAL (CORrelations And Logic) freeware. The CORAL models are based on representation of the molecular structure by simplified molecular input line entry system (SMILES). Three random splits into the training and the external validation sets have been examined. The ranges of statistical characteristics of these models are as follows: n = 18, r (2) = 0.748-0.815, s = 15.1 -17.5 (mg/mL), F = 47-71 (training set); n = 9, r (2) = 0.806-0.936, s = 12.5-17.5 (mg/mL), F = 29-103 (validation set). PMID- 20349135 TI - Investigation of transferrin polymorphism in Garole sheep. AB - The aim of this study was to determine the genetics of polymorph systems of Transferrin in Garole sheep breed. The present study was conducted on 95 adult Garole sheep comprising 52 ewes and 43 rams, maintained at Sheep and Goat Breeding Farm of West Bengal University of Animal and Fishery Sciences, West Bengal, during the period from April-September, 2009. The polymorphism of transferrin was determined through SDS-Polyacrylamide gel electrophoresis technique. It was found that the transferrin type was controlled by five codominant alleles (TfA, TfB, TfC TfD and TfE) in Garole sheep. These five alleles, because of co-dominant nature of inheritance, determined the occurrence of nine transferrin genotypes in the analyzed flock. Four (TfAA, TfBB, TfCC and TfDD) of these were homozygous and the remaining five (TfAD, TfBC, TfBD, TfCD and TfDE) heterozygous. It was found that the TfDD genotype (0.263) was predominant while TfDE genotype (0.042) was least common in the analyzed flock. Frequencies of other genotypes were as: TfCD(0.242), TfBD(0.126), TfCC(0.084), TfBB(0.074), TfAA(0.063), TfAD and TfBC (0.053 for each genotype ) in whole population. From the result it was found that in whole population combined, the heterozygotic genotypic frequency (0.516) was more than that of homozygotic genotypic frequency (0.484). Considerable variations were recognized in the frequencies of transferrin alleles. In the whole population frequencies of transferrin alleles were found to be TfA = 0.089, TfB = 0.163, TfC = 0.232, TfD = 0.495 and TfE = 0.021. Transferrin system has shown an absence of genetic equilibrium among the analyzed herd (chi2 value = 51.31). In conclusion, there were polymorphism in Transferrin types and the presence of differences among the frequencies of the five alleles by categories could be a source of genetic variation in Garole sheep. PMID- 20349136 TI - Heat shock protein 70 together with its co-chaperone CHIP inhibits TNF-alpha induced apoptosis by promoting proteasomal degradation of apoptosis signal regulating kinase1. AB - Inducible heat shock protein70 (HSP70) is one of the most important HSPs for maintenance of cell integrity during normal cellular growth as well as pathophysiological conditions. Apoptosis signal-regulating kinase (ASK) 1, a mammalian MAPKKK, activates the JNK and p38 pathways. Here we report a novel function of HSP70 in regulating TNF-alpha-induced cell apoptosis. Our study demonstrated that HSP70 physically interacted with ASK1 and promoted the ubiquitin-dependent proteasomal degradation of ASK1. CHIP (carboxyl terminus of the HSC70-interacting protein) which acted as a co-chaperone of HSP70 cooperated with HSP70 in regulating ASK1. We also found that TNF-alpha stimulated HSP70/CHIP/ASK1 association and through cooperating with CHIP, HSP70 inhibits TNF alpha-induced cell apoptosis both in over-expression and RNAi conditions. Structural analysis indicated that C-terminal domain of HSP70 was necessary for ASK1 degradation, and N- terminal domain of ASK1 was essential for its binding to HSP70. All these findings indicated that HSP70 and CHIP association is important for HSP70 in interacting with ASK1. Through forming the complex of HSP70/CHIP/ASK1, HSP70 promotes ASK1 proteasomal degradation and prevents TNF alpha-induced cell apoptosis. PMID- 20349137 TI - Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo. AB - Clinical management of chondrosarcoma remains a challenging problem, largely due to the toxicity and resistance of this tumor to conventional chemotherapy. Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different cell types in response to various stimuli, and has been shown to be down-regulated in many cancer tissues. In this study, mRNA and protein levels of PDCD5 were found to be up-regulated in cisplatin-treated SW1353 chondrosarcoma cells compared with untreated cells. Recombinant human PDCD5 (rhPDCD5) was also shown to sensitize chondrosarcoma cells to cisplatin-based chemotherapy, with inhibition of cell growth and apoptosis detected both in vitro and in vivo. Increased expression of Bax and decreased expression of Bcl-2 were also observed, along with release of cytochrome c from mitochondria into the cytosol. Additionally, cleavage of caspase-9 and caspase-3, as well as the cleavage of poly (ADP-ribose) polymerase (PARP), were detected, suggesting that sensitization of chondrosarcoma cells involves the intrinsic mitochondrial apoptosis pathway. In vivo, the treatment of a xenograft model of chondrosarcoma with rhPDCD5 and cisplatin significantly inhibited tumor cell proliferation and induced apoptosis compared to treatment with cisplatin alone. Overall, these data provide a theoretical basis for the administration of rhPDCD5 and cisplatin for the treatment of patients with chondrosarcoma. PMID- 20349138 TI - Late gadolinium enhancement gray zone in patients with hypertrophic cardiomyopathy. Comparison of different gray zone definitions. AB - To quantify heterogeneous tissue at the periphery of areas of fibrosis (gray zone) in patients with hypertrophic cardiomyopathy (HCM) with the use of two different techniques. Cardiac magnetic resonance with late gadolinium enhancement analysis was performed in 33 patients with HCM. Gray zone was evaluated with the use of two different techniques previously described in patients after myocardial infarction. LGE was present in 25 (78%) patients. There was no significant difference in total LGE mass at two different cut-off values [53.8 g (interquartile range, IQR 43.5-77.8 g) vs. 53.8 g (IQR 37.8-64.5 g), respectively, P = 0.49]. Significant difference in gray zone mass assessed with the use of two techniques was demonstrated (19.1 +/- 7.3 g vs. 50.8 +/- 47.8 g; P = 0.003). There was a strong correlation between total LGE and gray zone mass (r = 0.789, P = 0.0001 for first method and r = 0.951, P < 0.0001 for the second one, respectively). However, significant variability of gray zone mass (and extent expressed as % of left ventricular mass) in patients with similar LGE size/extent was observed. Moreover, LGE mass varied greatly in patients with similar gray zone size. Neither left ventricular mass, nor with maximal wall thickness correlated with extent of gray zone assessed with both methods. The studied techniques provided similar results with regard to total LGE but significant differences were observed in gray zone mass. Two patients may have similar extent (or absolute mass) of LGE, but strikingly discrepant gray zone size. PMID- 20349139 TI - The prognostic value of multidetector coronary CT angiography for the prediction of major adverse cardiovascular events: a multicenter observational cohort study. AB - To assess the prognostic value of coronary artery stenosis identification by coronary computed tomographic angiography (CCTA) for the prediction of major adverse cardiac events (MACE) in a multicenter prospective cohort study. We performed a prospective multicenter observational cohort study of symptomatic patients with suspected or known coronary artery disease (CAD) (n = 172; 57% male) undergoing CCTA in accordance to ACC/AHA Appropriateness Criteria from 4 sites in and around Paris, France, and followed for a mean duration of 22.0 +/- 4.5 months (interquartile range 18-26 months). Coronary arteries by CCTA were interpreted by physicians blinded to the patient characteristics for the presence or absence obstructive (>or=70% luminal diameter stenosis), as well as for plaque composition categorized as non-calcified, calcified or "mixed." MACE was defined as death, non-fatal myocardial infarction, unstable angina or target vessel revascularization. MACE event rates were compared between patients with or without obstructive plaque and with differing plaque compositions. MACE event rates were significantly higher in patients with obstructive coronary artery stenosis by CCTA compared to those without (61.1% vs. 3.9%, P < 0.01). In patients with obstructive stenosis, mixed (83.3% vs. 25.3%, P < 0.01) and calcified (94.4% vs. 50.7%, P < 0.01) plaque presence was significantly higher than in patients without obstructive stenosis, with no differences in prevalence of non-calcified plaque (27.8% vs. 20.8%, P = NS). For MACE, the negative predictive value of no observed coronary artery plaque was 100% in the follow-up period. In this prospective multicenter study of symptomatic patients with suspected or known CAD undergoing CCTAs interpreted by imagers blinded to patient characteristics, CCTA presence of plaque severity and composition successfully identifies patients at risk for incident MACE events. Importantly, a negative CCTA portends an extremely low risk for incidence MACE. PMID- 20349140 TI - Single and multiple CH (calponin homology) domain containing multidomain proteins in Arabidopsis and Saccharomyces: an inventory. AB - Genes for individual domains such as CH, lim, ankyrin, PH and RhoGAP, IQ motif, Ig_FLMN, spectrin, and EF hand probably existed in early evolution before there were plants, fungi or animals so that when we examine multidomain proteins in Arabidopsis, Saccharomyces, Dictyostelium or Homo Sapiens we encounter various combinations of such domains. While all of these four species express Fimbrin and EB1, the lists of CH containing multidomain proteins, however, differ in number and in type for each of them. There was no further great increase in the number of new single domain proteins. Still many new multidomain genes evolved--but far more so in metazoans--than in plants or fungi. In both plants and fungi only singlet CH domains but no doublets (other than those forming the Fimbrin quadruplet) were incorporated. That is in these two branches one finds no alpha actinin, dystrophin or filamin even though the individual building blocks (i.e. domains such as spectrin or IG-FLMN) were available in Arabidopsis. Possibly transposons create new chimeric multidomain genes by mixing and matching genes or gene fragments. PMID- 20349141 TI - Postconditioning reduces infarct size and cardiac myocyte apoptosis via the opioid receptor and JAK-STAT signaling pathway. AB - Brief intermittent episodes of ischemia and reperfusion could reduce infarct size, a phenomenon called "postconditioning" at the onset of reperfusion after a prolonged period of ischemia. To investigate whether the opioid receptors and signaling factor JAK-STAT might be responsible for the cardioprotection in ischemic postconditioning, and the possible molecular machinery of cardioprotection. Hundred and twenty healthy New Zealand rabbits were divided into six groups. The myocardial infarct size, cardiac myocyte apoptosis, BCL-2 and P-Stat3 protein expression were tested in the current study. The results suggested that ischemic postconditioning might increase BCL-2 protein expression by activating the opioid receptors and JAK-STAT signaling pathway, and also to reduce ischemia-reperfusion-induced cardiomyocyte apoptosis and to play a key role in myocardial protection. However, further research still needs to be done to unravel the underlying mechanisms. PMID- 20349143 TI - Molecular analysis shows differential expression of R-spondin1 in zebrafish (Danio rerio) gonads. AB - R-spondin1 (RSPO1) is a potential female-determining gene in human (Homo sapiens) and mouse (Mus musculus). Its differential expression in these mammals is correlated with signaling for sex determination. As a way of studying sex determination in fish we cloned and analyzed a RSPO1 gene in zebrafish (Danio rerio). Using real-time PCR, we observed that RSPO1 is expressed more strongly in ovaries than in testes, suggesting that RSPO1 may have a role in gonad differentiation. High RSPO1 expression was detected in some non-gonadal organs like muscle and kidneys. In situ hybridization results demonstrate that RSPO1 is expressed in premature germ cells, in oogonia and primary oocytes in ovaries and in spermatogonia and spermatocytes in testes. It is also expressed in gonad somatic cells during gonadal development: in granulosa cells and theca cells of early and late cortical-alveolar stage follicles in ovaries, and in Leydig cells in testes. This differential expression may indicate that RSPO1 has a role(s) in zebrafish gonad development and differentiation. By fusing zebrafish RSPO1 with a green fluorescent protein gene, we found that RSPO1 is located in the cytosol and Golgi apparatus but not the nucleus of fish epithelioma papulosum cyprinid (EPC) cells. These preliminary findings suggest some aspects of RSPO1 like differential expression linked to sex determination may be conserved in fish while other aspects like subcellular localization differ from the mammalian RSPO1. PMID- 20349142 TI - Characterization of a wheat HSP70 gene and its expression in response to stripe rust infection and abiotic stresses. AB - Members of the family of 70-kD heat shock proteins (HSP70 s) play various stress protective roles in plants. In this study, a wheat HSP70 gene was isolated from a suppression subtractive hybridization (SSH) cDNA library of wheat leaves infected by Puccinia striiformis f. sp. tritici. The gene, that was designated as TaHSC70, was predicted to encode a protein of 690 amino acids, with a molecular mass of 73.54 KDa and a pI of 5.01. Further analysis revealed the presence of a conserved signature that is characteristic for HSP70s and phylogenetic analysis demonstrated that TaHSC70 is a homolog of chloroplast HSP70s. TaHSC70 mRNA was present in leaves of both green and etiolated wheat seedlings and in stems and roots. The transcript level in roots was approximately threefold less than in leaves but light-dark treatment did not charge TaHSC70 expression. Following heat shock of wheat seedlings at 40 degrees C, TaHSC70 expression increased in leaves of etiolated seedlings but remained stable at the same level in green seedlings. In addition, TaHSC70 was differentially expressed during an incompatible and compatible interaction with wheat-stripe rust, and there was a transient increase in expression upon treatment with methyl jasmonate (MeJA) treatment. Salicylic acid (SA), ethylene (ET) and abscisic acid (ABA) treatments had no influence on TaHSC70 expression. These results suggest that TaHSC70 plays a role in stress related responses, and in defense responses elicited by infection with stripe rust fungus and does so via a JA-dependent signal transduction pathway. PMID- 20349144 TI - Single nucleotide polymorphisms of the prolactin receptor (PRLR) gene and its association with growth traits in Chinese cattle. AB - Genetic polymorphism of the prolactin receptor (PRLR) gene was detected by PCR SSCP and DNA sequencing methods in 665 individuals from five Chinese cattle breeds. The results showed that at the P1 locus, three observed genotypes (AA, AB and BB), two linked SNPs (G1267A and T1268C), and one missense mutation (S18N) within a putative signal peptide were determined. The frequencies of haplotypes A and B in the five breeds were 0.596-0.802 and 0.198-0.404, respectively. Polymorphism of the PRLR gene was shown to be significantly associated with growth traits in the Nanyang breed. Individuals with genotype BB had greater hucklebone width, body weight and average daily gain than those with genotype AA at 6 months old (P<0.01), as well as better body height, body length and heart girth when 6 months (P<0.05). This study revealed for the first time that the PRLR gene is a promising candidate gene that affects growth traits in cattle. PMID- 20349146 TI - In vitro culture of Keratinocytes from human umbilical cord blood mesenchymal stem cells: the Saigonese culture. AB - There have been many attempts to acquire and culture human keratinocytes for clinical purposes including from keratotome slices in media with fetal calf serum (FCS) or pituitary extract (PE), from skin specimens in media with feeder layers, from suction blister epidermal roofs' in serum-free culture and from human umbilical cord blood (hUCB) mesenchymal stem cells (MSCs) in media with skin feeder layers. Conversely this study was designed to investigate whether keratinocytes could be obtained directly from hUCB MSCs in vitro. It is widely established that mesenchymal stem cells from human umbilical cord blood have multipotent capacity and the ability to differentiate into disparate cell lineages hUCB MSCs were directly induced to differentiate into keratinocytes by using a specific medium composed of primary culture medium (PCM) and serum free medium (SFM) in a ratio 1:9 for a period of 7 days and tested by immunostain p63 and K1-K10. Cells thus cultured were positive in both tests, confirming the possibility to directly obtain keratinocytes from MSCs hUCB in vitro. PMID- 20349145 TI - An automated pipeline to screen membrane protein 2D crystallization. AB - Electron crystallography relies on electron cryomicroscopy of two-dimensional (2D) crystals and is particularly well suited for studying the structure of membrane proteins in their native lipid bilayer environment. To obtain 2D crystals from purified membrane proteins, the detergent in a protein-lipid detergent ternary mixture must be removed, generally by dialysis, under conditions favoring reconstitution into proteoliposomes and formation of well ordered lattices. To identify these conditions a wide range of parameters such as pH, lipid composition, lipid-to-protein ratio, ionic strength and ligands must be screened in a procedure involving four steps: crystallization, specimen preparation for electron microscopy, image acquisition, and evaluation. Traditionally, these steps have been carried out manually and, as a result, the scope of 2D crystallization trials has been limited. We have therefore developed an automated pipeline to screen the formation of 2D crystals. We employed a 96 well dialysis block for reconstitution of the target protein over a wide range of conditions designed to promote crystallization. A 96-position magnetic platform and a liquid handling robot were used to prepare negatively stained specimens in parallel. Robotic grid insertion into the electron microscope and computerized image acquisition ensures rapid evaluation of the crystallization screen. To date, 38 2D crystallization screens have been conducted for 15 different membrane proteins, totaling over 3000 individual crystallization experiments. Three of these proteins have yielded diffracting 2D crystals. Our automated pipeline outperforms traditional 2D crystallization methods in terms of throughput and reproducibility. PMID- 20349147 TI - Germination rates of perilla (Perilla frutescens (L.) Britton) mericarps stored at 4 degrees C for 1-20 years. AB - Periodic update of stored seeds is indispensable for sustainable use and preservation of plant genetic resources, and performance of this task requires precise data on the relationship between storage period and the germination rate of seeds after long-term storage. In this study, germination rates of pure strains of perilla (Perilla frutescens (L.) Britton var. crispa) were investigated for three strains by using the mericarps stored for 1-20 years at 4 degrees C under dry conditions. The germination rates were fairly good (65-70%) for 5-8 years after harvest, but dropped to almost 0% for mericarps stored more than 9 years. Mericarps that did not germinate were analyzed for viability by using 2,3,5-triphenyltetrazolium chloride. For old mericarps (stored more than 9 years), the germination rates and seed viability did not correlate. Further study on days required for germination of mericarps harvested each year was derived from our observation record, suggesting that germination rates and longevity of mericarp life were increasingly influenced by individual difference as the storage period lengthened. PMID- 20349148 TI - The effect of isosaponarin isolated from wasabi leaf on collagen synthesis in human fibroblasts and its underlying mechanism. AB - Wasabi has been used as an important spice in Japanese foods. The wasabi leaves were used as a cosmetic material, but its biological activities have not yet been examined. We investigated the effect of isosaponarin derived from wasabi leaf on collagen synthesis in human fibroblasts. The production of type I collagen in human fibroblasts was increased with treatment of wasabi leaf extract. Isosaponarin isolated from wasabi leaves belonged to the group of flavone glycoside, and was the key compound in collagen synthesis from the wasabi leaf ingredients. Isosaponarin increased the type I collagen production at the mRNA gene level. The treatment of isosaponarin did not influence the production of transforming growth factor-beta (TGF-beta) protein, but increased the production of TGF-beta type II receptor (TbetaR-II) protein and TbetaR-II mRNA. Prolyl 4 hydroxylase (P4H) protein and P4H mRNA were increased by treatment with isosaponarin. Heat shock protein 47 (HSP47) was not increased by treatment with isosaponarin. These results suggested that isosaponarin increased collagen synthesis in human fibroblasts, caused by up-regulated TbetaR-II and P4H production. PMID- 20349149 TI - Effect of prenylated flavonoids and chalcones isolated from Artocarpus species on platelet aggregation in human whole blood. AB - Five prenylflavonoids and two prenylchalcones from Artocarpus lowii King, A. scortechinii King and A. teysmanii Miq., and acetylated derivatives of cycloheterophyllin and artonin E were investigated for their ability to inhibit arachidonic acid (AA), collagen and adenosine diphosphate (ADP)-induced platelet aggregation in human whole blood by using an electrical impedance method. Among the tested compounds, only cycloheterophyllin inhibited AA-induced platelet aggregation with an IC(50) value of 100.9 microM. It also showed strong inhibition against ADP-induced aggregation, with an IC(50) value of 57.1 microM. Isobavachalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone, cycloartobiloxanthone, artonin E and artonin E triacetate showed selective inhibition against ADP-induced aggregation, with IC(50) values ranging from 55.3 to 192.0 microM, but did not show such effect against other inducers. PMID- 20349150 TI - Constituents of the lichen Peltigera dolichorrhiza. AB - A new aromatic derivative, 5-(3,4-dihydroxyphenyl)-3-methylcyclohex-2-enone (1), and three known compounds, peltigerine, solorinine, and phenyl butanoid, were isolated from the MeOH extract of the lichen Peltigera dolichorrhiza (Peltigeraceae). Their structures were determined by 1D and 2D nuclear magnetic resonance and mass spectroscopy analysis. PMID- 20349151 TI - New flavonoids with 2BS cell proliferation promoting effect from the seeds of Trigonella foenum-graecum L. AB - Ten flavonoids were isolated from the ethyl acetate-soluble fraction of the ethanolic extract of the seeds of Trigonella foenum-graecum and their structures were elucidated on the basis of spectroscopic methods to be 5,7,3'-trihydroxy-5' methoxylisoflavone (1), biochanin A (2), formononetin (3), irilone (4), tricin (5), daidzein (6), calycosin (7), orientin-2''-O-p-trans-coumarate (8), vitexin 2''-O-p-trans-coumarate (9), and tricin-7-O-beta-D: -glucopyranoside (10). Compounds 1 and 8 are new flavonoids, and 8 and 9 strongly promoted 2BS cell proliferation induced by H(2)O(2). PMID- 20349152 TI - An age-structured model for the potential impact of generalized access to antiretrovirals on the South African HIV epidemic. AB - A simple mathematical model (Granich et al., Lancet 373:48-57, 2009) suggested recently that annual HIV testing of the population, with all detected HIV(+) individuals immediately treated with antiretrovirals, could lead to the long-term decline of HIV in South Africa and could save millions of lives in the next few years. However, the model suggested that the long-term decline of HIV could not be achieved with less frequent HIV testing. Many observers argued that an annual testing rate was very difficult in practice. Small scale trials are nevertheless in preparation. In this paper, we use a more realistic age-structured model, which suggests that the recent high levels of reported condom use could already lead to a long-term decline of HIV in South Africa. The model therefore suggests that trials with for example 20% of the population tested each year would also be interesting. They would have similar (though smaller) advantages in terms of reduction of mortality and incidence, would be much easier to generalize to larger populations, and would not lead to long term persistence of HIV. Our model simulations also suggest that the age distribution of incidence has changed considerably over the past 20 years in South Africa. This raises some concern about an assumption presently used in EPP/Spectrum, the software used by UNAIDS for its estimates. PMID- 20349153 TI - The site-frequency spectrum of linked sites. AB - The site-frequency spectrum, representing the distribution of allele frequencies at a set of polymorphic sites, is a commonly used summary statistic in population genetics. Explicit forms of the spectrum are known for both models with and without selection if independence among sites is assumed. The availability of these explicit forms has allowed for maximum likelihood estimation of selection, developed first in the Poisson random field model of Sawyer and Hartl, which is now the primary method for estimating selection directly from DNA sequence data. The independence assumption, which amounts to assume free recombination between sites, is, however, a limiting case for many population genetics models. Here, we extend the site-frequency spectrum theory to consider the case where the sites are completely linked. We use diffusion approximation to calculate the joint distribution of the allele frequencies of linked sites for models without selection and for models with equal coefficient selection. The joint distribution is derived by first constructing Green's functions corresponding to multiallele diffusion equations. We show that the site-frequency spectrum is highly correlated between frequencies that are complementary (i.e., sum to 1), and the correlation is significantly elevated by positive selection. The results presented here can be used to extend the Poisson random field to allow for estimating selection for correlated sites. More generally, the Green's function construction should be able to aid in studying the genetic drift of multiple alleles in other cases. PMID- 20349154 TI - Narrative review: should teaching of the respiratory physical examination be restricted only to signs with proven reliability and validity? AB - OBJECTIVE: To review the reported reliability (reproducibility, inter-examiner agreement) and validity (sensitivity, specificity and likelihood ratios) of respiratory physical examination (PE) signs, and suggest an approach to teaching these signs to medical students. METHODS: Review of the literature. We searched Paper Chase between 1966 and June 2009 to identify and evaluate published studies on the diagnostic accuracy of respiratory PE signs. RESULTS: Most studies have reported low to fair reliability and sensitivity values. However, some studies have found high specificites for selected PE signs. None of the studies that we reviewed adhered to all of the STARD criteria for reporting diagnostic accuracy. CONCLUSIONS: Possible flaws in study designs may have led to underestimates of the observed diagnostic accuracy of respiratory PE signs. The reported poor reliabilities may have been due to differences in the PE skills of the participating examiners, while the sensitivities may have been confounded by variations in the severity of the diseases of the participating patients. IMPLICATION FOR PRACTICE AND MEDICAL EDUCATION: Pending the results of properly controlled studies, the reported poor reliability and sensitivity of most respiratory PE signs do not necessarily detract from their clinical utility. Therefore, we believe that a meticulously performed respiratory PE, which aims to explore a diagnostic hypothesis, as opposed to a PE that aims to detect a disease in an asymptomatic person, remains a cornerstone of clinical practice. We propose teaching the respiratory PE signs according to their importance, beginning with signs of life-threatening conditions and those that have been reported to have a high specificity, and ending with signs that are "nice to know," but are no longer employed because of the availability of more easily performed tests. PMID- 20349155 TI - A randomized community-based intervention trial comparing faith community nurse referrals to telephone-assisted physician appointments for health fair participants with elevated blood pressure. AB - OBJECTIVE: To measure the effect of faith community nurse referrals versus telephone-assisted physician appointments on blood pressure control among persons with elevated blood pressure at health fairs. METHODS: Randomized community-based intervention trial conducted from October 2006 to October 2007 of 100 adults who had an average blood pressure reading equal to or above a systolic of 140 mm Hg or a diastolic of 90 mm Hg obtained at a faith community nurse-led church health event. Participants were randomized to either referral to a faith community nurse or to a telephone-assisted physician appointment. The average enrollment systolic blood pressure (SBP) was 149 +/- 14 mm Hg, diastolic blood pressure (DBP) was 87 +/- 11 mm Hg, 57% were uninsured and 25% were undiagnosed at the time of enrollment. RESULTS: The follow-up rate was 85% at 4 months. Patients in the faith community nurse referral arm had a 7 +/- 15 mm Hg drop in SBP versus a 14 +/- 15 mm Hg drop in the telephone-assisted physician appointment arm (p = 0.04). Twenty-seven percent of the patients in the faith community nurse referral arm had medication intensification compared to 32% in the telephone-assisted physician appointment arm (p = 0.98). CONCLUSIONS: Church health fairs conducted in low-income, multiethnic communities can identify many people with elevated blood pressure. Facilitating physician appointments for people with elevated blood pressure identified at health fairs confers a greater decrease in SBP than referral to a faith community nurse at four months. PMID- 20349156 TI - Defensive medicine and tort reform: a wide view. PMID- 20349157 TI - Dihydroprogesterone increases the gene expression of myelin basic protein in spinal cord of diabetic rats. AB - Alterations in myelin membranes, as well as in the expression of myelin proteins have been reported in experimental models of diabetes. Data here reported show for the first time that the mRNA levels of two isoforms of myelin basic protein (MBP), 18.5 and 21.5 kDa, are decreased in the spinal cord of streptozotocin treated rats and that treatment with a neuroactive steroid, such as progesterone (P), may counteract this effect. Interestingly, metabolism of progesterone into dihydroprogesterone (DHP) by the enzyme 5alpha-reductase seems to exert an important role in such an effect. As here demonstrated, 5alpha-reductase mRNA and DHP levels are reduced by diabetes in spinal cord, but treatment with P, is able to counteract these effects. Moreover, treatment with DHP is able to mimic the effect of P on MBP gene expression. Thus, the effects of P here observed are due to its enzymatic conversion into DHP. Because DHP, like P, interacts with P receptor (PR), the present results may suggest the importance to analyze the effects of PR modulators as tools of therapeutic strategies for diabetic complications occurring in nervous system. PMID- 20349158 TI - Primitive neuroectodermal tumor of the jejunum; a case report and literature review. AB - OBJECTIVE AND IMPORTANCE: The aim of this paper is to report an unusual presentation of extranodal follicular dendritic cell tumor of neck with spinal metastasis. Follicular dendritic cells are nonlymphoid immune accessory cells present in the germinal centers of lymphoid follicles and play a crucial role in the induction and maintenance of the humoral immune response. Tumors from these cells are rare and treatment modality poorly defined. CLINICAL PRESENTATION: A 37 year-old lady presented with recurrent neck swelling which was initially reported as malignant paraganglioma. The primary disease was treated with surgery and radiotherapy. Eleven years later, the patient presented with metastasis to the spinal cord. Subsequent immunohistochemical analysis of the primary site tumor and the metastatic deposits revealed it to be a follicular dendritic cell tumor. INTERVENTION: The patient was treated with surgery followed by radiotherapy to spine, and one and half year after treatment, the patient is doing well and has regained complete motor functions. CONCLUSION: Metastasis to spinal cord for follicular dendritic cell tumor is very rare, and to the best of our knowledge, no such case has been previously reported in the scientific literature so far. In the present case, good local control was achieved with initial surgery and radiotherapy but resulted in distant failure after 11 years. This underlines the need for adjuvant systemic therapy, and understanding the biology of the tumor may help in formulating targeted therapy in the future for this rare disorder. PMID- 20349159 TI - Activation of blood coagulation in chronic urticaria: pathophysiological and clinical implications. [corrected] PMID- 20349161 TI - Estimation of 123I-IMP arterial blood activity from dynamic planar imaging of the chest using a graph plot method for the quantification of regional cerebral blood flow. AB - PURPOSE: I-123-labeled N-isopropyl-p-iodoamphetamine ((123)I-IMP) is used for the measurement of regional cerebral blood flow (rCBF). A continuous or single arterial blood sampling (ABS) is necessary to estimate an integral of arterial input function (AIF) for the measurement of rCBF by using a microsphere model analysis. Therefore, a method of measuring rCBF without any blood sampling is desired. The aim of this study was to establish a method to estimate the AIF from the time-activity curve of the lungs after an injection of (123)I-IMP, using a regression analysis for the measurement of rCBF without any blood sampling. MATERIALS AND METHODS: Thirty-seven prospective studies in 10 consecutive patients were enrolled. A chest planar dynamic imaging for 3 min and continuous ABS for 5 min after a bolus injection of 167MBq (123)I-IMP were performed in all studies. Data from the chest imaging were analyzed in comparison with ABS data (AIF(5)) in the first 10 studies, and an equation for estimation yielding accurate AIF(5) from the total counts cleared from the lungs, during 5 min after injection of (123)I-IMP (TCL(5)), was derived. The validity of the proposed method was evaluated in the subsequent 27 studies. RESULTS: A good correlation was obtained between the AIF and TCL by regression analysis in the first 10 studies (r = 0.94, P < 0.001). An equation for the estimation of AIF by the regression analysis in the first 10 studies was defined as follows: estimated AIF = 2147 + 4.174 x TCL(5). In the subsequent 27 studies, a good linear correlation was obtained between the measured and the estimated AIF(5) by using the equation (r = 0.79, P < 0.001). CONCLUSION: AIF(5) can be accurately estimated from TCL(5). Therefore, estimated AIF(5) can be used for the measurement of rCBF instead of ABS data. PMID- 20349162 TI - Elevated osteopontin expression and proliferative/apoptotic ratio in the colorectal adenoma-dysplasia-carcinoma sequence. AB - Colorectal cancer progression is characterized by altered epithelial proliferation and apoptosis and by changed expression of tumor development regulators. Our aims were to determine the proliferative/apoptotic epithelial cell ratio (PAR) in the adenoma-dysplasia-carcinoma sequence (ADCS), and to examine its association with osteopontin (OPN), a previously identified protein product related to cancer development. One mm diameter cores from 13 healthy colons, 13 adenomas and 13 colon carcinoma samples were included into a tissue microarray (TMA) block. TUNEL reaction and Ki-67 immunohistochemistry were applied to determine the PAR. The osteopontin protein was also immunodetected. Stained slides were semiquantitatively evaluated using digital microscope and statistically analyzed with logistic regression and Fisher's exact test. The PAR continuously increased along the ADCS. It was significantly (p < 0.001) higher in cancer epithelium (8.84 +/- 7.01) than in adenomas (1.40 +/- 0.78) and in normal controls (0.89 +/- 0.21) (p < 0.001). Also, significant positive correlation was observed between elevated PAR and the expression of osteopontin. Cytoplasmic OPN expression was weak in healthy samples. In contrast, cytoplasmic immunoreaction was moderately intensive in adenomas, while in colon cancer strong, diffuse cytoplasmic immune staining was detected. Increasing PAR and OPN expression along ADCS may help monitoring colorectal cancer progression. The significantly elevated OPN protein levels we found during normal epithelium to carcinoma progression may contribute to the increased fibroblast-myofibroblast transition determining stem cell niche in colorectal cancer. PMID- 20349163 TI - Obesity, epidural analgesia, and subcostal incision are risk factors for postoperative desaturation. AB - PURPOSE: This study was designed to determine the incidence of oxygen desaturation after upper abdominal surgery during the first 48 hr on general surgical wards and also to identify risk factors for oxygen desaturation. METHODS: This descriptive study was conducted in 206 patients not expected to receive supplemental oxygen postoperatively who were undergoing upper abdominal surgery in a tertiary care university hospital. Desaturation was classified either as constant, i.e., oxygen saturation < 90% for > three minutes or < 85% once or as episodic, i.e., when oxygen saturation is decreased by > or = 5% below baseline for one to two minutes ten times or more during the night period. Possible risk factors were elderly patients (> 70 yr), obesity (body mass index [BMI] > 25 kg.m(-2)), smoking, surgical time > 180 min, postoperative pain control methods, intraoperative blood loss, and site of incision. RESULTS: Of the 206 patients enrolled, 171 were retained for analysis. Desaturation occurred in 65 patients (38%). Forty-eight of these had constant hypoxemia with nadir oxygen saturation values ranging from 71-89%. The remaining 17 patients experienced nocturnal episodic hypoxemia. After multivariate analysis, the three factors that correlated with postoperative desaturation were BMI > 25 (adjusted odds ratio [OR] 3.06; 95% confidence interval (CI) 1.38-6.79; P = 0.006), subcostal incision (OR 2.68; 95%CI 1.34-5.38; P = 0.005), and neuraxial opioids (OR 2.44; 95%CI 1.21 4.91; P = 0.013). CONCLUSION: Oxygen desaturation is common after upper abdominal surgery, and the risk factors are obesity, a subcostal incision, and neuraxial opioid administration. PMID- 20349165 TI - [Editorial on the main topic: femoroacetabular impingement]. PMID- 20349164 TI - A localizing circumferential compression device delayed death after artificial eastern diamondback rattlesnake envenomation to the torso of an animal model in a pilot study. AB - Nearly all prior studies to delay onset of systemic toxicity and death after snake bite use a model of distal extremity envenomation. In the first of a series of planned studies using snake venoms with different toxicity profiles, the application of a novel device in a new model of torso envenomation in the setting of Eastern Coral Snake (Micrurus fulvius) venom (a potent neurotoxin) envenomation showed promise by delaying systemic intoxication. In this pilot study, we investigated this novel localizing circumferential compression (LoCC) device's ability to delay onset of life threatening systemic toxicity after Eastern Diamondback Rattlesnake (Crotalus adamanteus) envenomation, a potent hemotoxic and myotoxic venom. With university approval, four juvenile female pigs (22-25 kg) were anesthetized, sedated, and intubated but not paralyzed to allow for spontaneous respirations. Each animal was injected subcutaneously with 50 mg of C. adamanteus venom in identical preselected areas of the trunk. After 1 min, two treatment animals had the LoCC device applied; two control animals had no intervention. Vital signs were recorded every 10 min for the first 2 h and every 30 min thereafter. Endpoints included cardiovascular collapse (fatal arrhythmia, loss of mean arterial pressure, or pulse) or respiratory arrest (<3 breaths/min, saturation < 80%) or survival to 7 h. The pigs in the treatment group reached an endpoint at an average time of 355 (+/-65) min compared with control 32 (+/-3.5) min (p < 0.04). In this pilot study, the LoCC device significantly delayed onset of systemic symptoms and death after torso envenomation with Eastern Diamondback Rattlesnake venom in this model. PMID- 20349166 TI - [Open therapy of femoroacetabular impingement]. AB - OBJECTIVE: Elimination of an intraarticular femoroacetabular impingement conflict. Creation of a pain-free, normal range of motion of the hip. INDICATIONS: Femoroacetabular impingement of any type (cam/pincer) and any localization (anterior/posterior). CONTRAINDICATIONS: Absolute: advanced hip osteoarthritis, local infections around the hip. Relative: excessive acetabular retroversion with deficiency of the posterior wall. SURGICAL TECHNIQUE: Lateral decubitus position. Straight lateral incision centered over the greater trochanter. Entering of the Gibson interval. Digastric trochanteric osteotomy with protection of the medial circumflex femoral artery. Opening of the interval between the piriformis and the gluteus minimus muscle. Z-shaped capsulotomy. Dislocation of the femoral head. Detachment of the labrum. Trimming of the excessive acetabular rim. Refixation of the labrum. Creation of a sufficient femoral head-neck offset. Suture of the capsule. Refixation of the trochanter. POSTOPERATIVE MANAGEMENT: During hospital stay, intensive mobilization of the hip joint using a continuous passive motion machine with a maximum flexion of 90 degrees . No active abduction and passive adduction over the body's midline. Maximum weight bearing 10-15 kg for 6 weeks. Subsequently, first clinical and radiographic follow-up. Deep venous thrombosis prophylaxis until full weight bearing. RESULTS: Short- and mid-term results showed an improvement of the postoperative clinical score (Merle d'Aubigne Score) in 95% of all patients, depending on the individual degenerative joint alterations at the time of surgery. Good to excellent results were obtained in 91% of all cases. Cumulative 5-year survival was 91% (endpoint total hip arthroplasty or poor Merle d'Aubigne Score). Long-term results are not available yet. PMID- 20349167 TI - [Treatment of femoroacetabular impingement using a minimally invasive anterior approach]. AB - OBJECTIVE: Treatment of femoracetabular impingement to prevent or delay the development of secondary osteoarthritis of the hip. Improvement of the mechanical limitation of the range of motion of the hip joint. Pain-free movement of the hip. INDICATIONS: Femoroacetabular impingement including a cam impingement, a pincer impingement, as well as mixtures of both types. Osteoarthritis of the hip joint grades 1-3 according to Kellgren induced by a femoroacetabular impingement. CONTRAINDICATIONS: Pincer impingement with the necessity of an osteotomy in acetabula malaligned in retroversion. Severe osteoarthritis grade 4 according to Kellgren. Hip infection. SURGICAL TECHNIQUE: Supine position of the patient. Longitudinal incision of 5-6 cm in line with the medial border of the anterior superior iliac spine at the level of the greater trochanter, two thirds cranially and one third distally of the tip of greater trochanter. Minimally invasive anterior approach in a modified technique of the Smith-Petersen approach with cutting of the fascia and preservation of the lateral femoral cutaneous nerve running between the two layers of the fascia. Blind preparation between the sartorius muscle and the tensor fasciae latae muscle. Preparation and T-shaped opening of the joint capsule in the direction of the capsule fibers and the anterior iliofemoral ligament. Removal of additional bone mostly in the ventral area of the femoral neck with angled and straight chisels. Using different positions of the leg helps to reach the more medial and lateral areas of the femoral neck. A trimming of the acetabulum with or without refixation of the labrum in the anterior and anterocranial acetabular rim is also possible. Documentation using fluoroscopy. Wound closure. POSTOPERATIVE MANAGEMENT: Prophylaxis of deep venous thrombosis. Early functional mobilization with unlimited range of motion of the hip joint. The amount of weight bearing is influenced by the amount of bone resection during trimming. In most cases, full weight bearing is possible. In cases of extensive bone resection (more than one fourth of the femoral neck diameter), gradual increase of weight bearing over 6 weeks. RESULTS: After a follow-up of 15.5 +/- 6.8 months, 65 patients (20 female, 45 male; 70 hip joints) aged 40.2 +/- 11.3 years showed an improvement of the Oxford Hip Score from 34.3 +/- 9.8 points preoperatively to 16.3 +/- 11.0 points and of the WOMAC (Western Ontario and McMaster Universities) Score from 60.8 +/- 23.1 points to 84.0 +/- 15.1 points at the latest follow-up examination. The impingement test was negative in all cases. In twelve cases, a temporary hypesthesia of the cranial innervation area of the lateral femoral cutaneous nerve was reported. PMID- 20349168 TI - [Arthroscopic resection of the cam deformity of femoroacetabular impingement]. AB - OBJECTIVE: Resection of the cam deformity of the femoral head-neck junction in order to avoid femoroacetabular impingement and the development of secondary damage to the anterolateral acetabular rim. INDICATIONS: Femoroacetabular cam impingement. Initial femoroacetabular pincer impingement. Advanced femoroacetabular pincer impingement with degenerative tear of the labrum. CONTRAINDICATIONS: Femoroacetabular pincer impingement with significant retroversion and intact acetabular labrum, coxa profunda or circumferential ossification of the labrum. Advanced osteoarthritis. SURGICAL TECHNIQUE: Arthroscopy of the peripheral compartment via three portals with and without traction. The proximal anterolateral portal is used for the arthroscope, instrumentation is done via the anterior and classic anterolateral portal. After resection of the zona orbicularis and the inner parts of the iliofemoral ligament, the anterolateral cam deformity is resected without traction via the anterior portal. After distraction of the head from the acetabulum, the lateral and posterolateral cam deformity is trimmed via the classic anterolateral portal. POSTOPERATIVE MANAGEMENT: Pain-controlled progression to full weight bearing over 1-4 weeks, continuous passive motion therapy and stationary bike for 6 weeks in order to avoid intraarticular adhesions. RESULTS: From 2004 through early 2007, 72 hip arthroscopies were performed for femoroacetabular impingement. So far, 48 patients (25 men, 23 women, mean age 37 years [17-65 years]) were followed up. After a mean follow-up of 18 months, the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was significantly improved from 65 +/- 21 to 82 +/- 18 and the NAHS (Non Arthritic Hip Score) from 57 +/- 19 to 78 +/- 19. COMPLICATIONS: two persistent branch lesions of the lateral femoral cutaneous nerve. One patient was surgically dislocated after 8 months for the treatment of a significant retroversion of the acetabulum; one patient underwent total hip arthroplasty after 1 year. PMID- 20349169 TI - [Intraoperative pedography]. AB - THE PROBLEM: Intraoperative assessment of the restored or maintained physiological plantar force distribution during foot and ankle corrections is very difficult. THE SOLUTION: Intraoperative assessment of the restored or maintained physiological plantar force distribution during foot and ankle corrections with intraoperative pedography (IP). SURGICAL TECHNIQUE: Bilateral pedography with the "Kraftsimulator Intraoperative Pedographie" (KIOP, R Innovation, Coburg, Germany) and a mat sensor (Pliance, custom-made, Novel, Munich, Germany) in the preparation room under anesthesia. Three measurements each side with a total force corresponding to half of the body weight are performed. Transfer of the patient to the operating room and correction including definitive internal fixation following the planning and findings. Sterile draping of the sensor mat and usage of a sterile KIOP for IP of the operated foot with three measurements, and assessment and comparison with preoperative, contralateral and physiological pedographic findings. When a correction of the force distribution is indicated, modification of the correction and internal fixation and renewed IP. POSTOPERATIVE MANAGEMENT: IP has no influence on the postoperative management. RESULTS: IP was validated in an earlier study. In a prospective, randomized, controlled clinical study, the potential clinical benefit of IP in a sufficient number of cases in comparison to cases treated without IP was analyzed. 100 cases were included until April 11, 2008. 52 patients were randomized for the use of IP. Mean interruption of the operative procedure for the IP was 321 +/- 39 s. In 24 of the 52 patients (46%), the correction was modified after IP during the same operation. The changes were done most commonly in midfoot correction arthrodeses (64%), and least commonly in subtalar joint arthrodeses (25%). PMID- 20349170 TI - [Minimally Invasive Acromioclavicular Joint Reconstruction (MINAR)]. AB - OBJECTIVE: Reduction and retention of an acromioclavicular (AC) joint dislocation with a button/suture augmentation cerclage (Flip tack, Karl Storz, Tuttlingen, Germany). INDICATIONS: Dislocation of the AC joint (Rockwood III and V). Chronic instabilities in combination with autogenous replacement of the coracoclavicular ligaments. Lateral clavicular fracture with rupture of the coracoclavicular ligaments. CONTRAINDICATIONS: Patients in poor general condition. Local soft tissue infection. Low-degree dislocation of AC joint (Rockwood I und II). Fracture of the clavicular shaft. Chronic instabilities without ligament replacement. SURGICAL TECHNIQUE: The coracoid process is exposed by a 3 cm long skin incision. A hole is drilled through the coracoid process with the help of a specific aiming device. The suture cerclage is connected to two buttons. One of the buttons is then pushed through the coracoid process. The button is flipped and the suture thereby fixed to the coracoid process. The other anchor is pulled through a hole in the clavicle and the cerclage is secured with a surgical knot after reduction of the AC joint. POSTOPERATIVE MANAGEMENT: Application of an abduction splint for 4 weeks (15 degrees). RESULTS: 23 patients with an acute luxation of the AC joint were operated with a minimally invasive coracoclavicular cerclage (five patients with Rockwood type III and 18 patients with Rockwood type V). Mean operative time was 28.6 min. Perior postoperative complications such as nerve and vascular injuries, thoracic injuries, infection, thrombosis, and embolism did not occur. The mean Constant Score was 94.1 points (73-100 points) after a mean of 23.3 months (18-28 months). In two cases, a slight loss of reposition of less than half of the clavicle width in comparison with the contralateral side was observed. PMID- 20349171 TI - [Computer-assisted total knee replacement (TKR) using Orthopilot navigation system]. AB - OBJECTIVE: Reproducible, precise implantation of a bicondylar knee prosthesis considering size of implant, axial conditions in coronal and sagittal planes, rotation, and ligament tension in extension and flexion. INDICATIONS: Progressive painful gonarthrosis, when conservative treatment is no longer an option. Revision of unicondylar prosthesis. CONTRAINDICATIONS: General contraindications to bicondylar knee replacement. Revision after bicondylar replacement. Severe limitation of hip joint mobility, e.g., after arthrodesis of the hip joint or ipsilateral hip joint ankylosis. Morbid obesity. SURGICAL TECHNIQUE: Approach to the knee joint for alloarthroplasty. Placement of the screws and fixation of the infrared reflectors at femur and tibia. After adjustment of the double camera, collection of kinematic data via standardized motion patterns and identification of predetermined anatomic landmarks at the knee and ankle joint. By means of this data, controlled resection of the tibia, determination of the ligament tension in extension and flexion, planning of the femoral osteotomies, controlled distal resection of the femur. Following intraoperative verification of the distal femur resection, navigation of the position of the femur to complete femoral resection. Placement of the trial components, determination of the tibial onlay thickness, adjustment of the rotation of the tibial component, and final preparation of the tibial shaft. Preparation of the patella by resection of osteophytes, denervation, and possibly onlay patellar resection using a saw. Finally, implantation of the tibial component (cemented or noncemented), the tibial onlay, the femoral component (cemented or noncemented), and possibly cementation of the patellar onlay. After hardening, control of knee movement in straight position and wound closure in layers. POSTOPERATIVE MANAGEMENT: Early functional treatment using continuous passive motion device. Pain-adapted increase of weight bearing. Low-molecular-weight heparin for 5-6 weeks. RESULTS: Meanwhile, several studies have demonstrated that computer navigation helps to provide more accuracy in implant positioning, compared with conventional techniques in total knee replacement. Long-term survival of the implants promises to be superior after physiological leg axis restoration. Own results: 100 consecutive implantations: average duration of surgery 80 min, blood loss 360 ml, one deep infection (healed after early revision), one arthrofibrosis requiring revision surgery, average range of motion on the day of discharge 110 degrees in flexion (90-120 degrees) and full extension, after 3 months average 125 degrees in flexion (90-140 degrees). No clinical signs of instability. Postoperative radiologic evaluation with standard radiographs of the knee joint in coronal and sagittal planes took place right after surgery and again after 3 months. PMID- 20349172 TI - [Treatment of lateral humeral condyle fractures in children]. AB - OBJECTIVE: Surgical treatment of lateral humeral condyle fractures with reduction and retention in order to prevent lasting malalignment, pseudarthrosis, and joint instability. INDICATIONS: Absolute: fractures with a complete dislocation or those in which plaster-free control X-ray on day 4 shows a gap of > 2 mm. Relative: complete fractures of the lateral humeral condyle which demonstrate a dislocation < or = 2 mm on follow-up. CONTRAINDICATIONS: Incomplete, so-called hanging fractures of the lateral humeral condyle without notable secondary dislocation on follow-up. SURGICAL TECHNIQUE: Open reduction of the lateral humeral condyle via a lateral approach to the elbow joint. In smaller children (< 5 years of age) fixation with Kirschner wires. In older children (> or = 5 years of age) or in cases requiring compression radial screw fixation is recommended. In all cases, suture repair of the periosteum is advisable. POSTOPERATIVE MANAGEMENT: Long upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3-4 weeks postoperatively. Implants are removed following consolidation (confirmed by X-ray) after approximately 2-3 months. Routine physiotherapy is normally not required. RESULTS: From January 1, 1999 to December 31, 2006, 85 children with a median age of 6.1 years had lateral condyle fracture of the humerus treated. 47 patients underwent surgery. Of these, 31 were treated with a combination of screw and Kirschner wire fixation, 13 with a single screw, and in three cases, the fracture was fixed with Kirschner wires only. After a median of 8.6 weeks (range, 5.0-17.1 weeks), implants were removed. Median follow-up time was 6 months (range, 2-50 months). There were no late complications in this series (e.g., lack of consolidation, pseudarthrosis). In five cases, hyposensitivity of the skin above the proximal aspect of the radial bone was noted postoperatively. This problem was solved in all instances within the following 6 months. A telephone survey with a response rate of 87% (74 patients) was undertaken in September 2007. Three children noted a minimal deficiency in strength of the injured arm in comparison to the contralateral extremity. One of these children additionally stated a minor flexion deficit of the elbow already present at the last follow-up in the outpatient clinic, which showed no progress. None of the patients had to be referred back to the outpatient clinic because of persistent problems and/or unacceptable results. PMID- 20349173 TI - [Replacement of the Glenoid Using a Reconstruction Socket (EPOCA RECO]. AB - OBJECTIVE: Alleviation of pain, restoration of function and active range of motion in the shoulder in case of cuff tear arthropathy. INDICATIONS: Cuff tear arthropathy with an insufficient coracoacromial arch and salvage operation of failed hemiprosthesis or reverse shoulder prosthesis. CONTRAINDICATIONS: Active or chronic infections. Lesions of the plexus. Insufficiency of deltoid muscle or subscapularis muscle. Neurologic diseases. Young active patients. SURGICAL TECHNIQUE: Deltopectoral approach. Resection of the humeral head and removal of the failed implant, respectively. Periarticular arthrolysis with preservation of neurovascular structures. Exposure of the glenoid and three-point fixation of the reconstruction socket (EPOCA RECO) at the glenoid, the acromion and the coracoid process. Cemented fixation of the polyethylene inlay. Cemented or cementless implantation of the humeral stem in 25 degrees retroversion related to the long axis of the forearm. Reconstruction of the subscapularis muscle. POSTOPERATIVE MANAGEMENT: Bedding of the arm in a Gilchrist brace. Passive and active- assisted exercises including continuous passive motion. RESULTS: From 2002 to 2007, a total of 35 reconstruction sockets (EPOCA RECO) were implanted in 34 patients (six men, 28 women - one bilateral implantation was performed at an interval of 8 months in a female patient). Five EPOCA RECO implants had to be removed due to major complications. Three patients died, another three patients refused the follow-up examination. The remaining 23 patients (three men, 20 women, average age at the time of surgery 76 years [64-88 years]) were examined 2 years (4-60 months) postoperatively. The preoperative gender-related Constant Score was 21 and improved significantly (p < 0.001) to 58 postoperatively. The pain was significantly reduced. Range of motion for active elevation, internal and external rotation was improved (preoperatively/ postoperatively): elevation 37.2 degrees/65 degrees; internal rotation 14.8%/50%; external rotation 11.3%/47.5%. All patients would undergo the operation again. Overall, there were five major and two minor complications (complication rate 20%). PMID- 20349174 TI - [A modified posterolateral approach for the treatment of tibial plateau fractures]. AB - OBJECTIVE: Open reduction and internal fixation of posterolateral tibial plateau fractures. INDICATIONS: Tibial plateau fractures involving the posterolateral quadrant. CONTRAINDICATIONS: Critical soft-tissue conditions. Tibial plateau fractures which do not involve the posterolateral quadrant. SURGICAL TECHNIQUE: 90 degrees side positioning on the contralateral side, skin incision along the fibular head, exposure of the peroneal nerve, lateral arthrotomy and exposure of the joint, dissection of the popliteal cavity between the lateral head of the gastrocnemius muscle and soleus muscle. Blunt preparation between popliteus muscle and soleus muscle under preservation of the popliteal artery and vein. Sharp dissection of the soleus muscle from the dorsal parts of fibula and tibia until the peroneal nerve at the fibular neck enters into the muscle. Exposure of the posterolateral tibial head. The dorsal joint capsule and the popliteal corner are prevented from any soft-tissue damage. Visual control of fracture reduction by viewing in the joint gap through lateral arthrotomy. Reduction of the fracture from dorsal with pointed reduction forceps. A conventional or locking radius T plate can be pinched off with lateral cutters and anatomically bent for fracture fixation and is dorsally fixed at the tibial plateau. POSTOPERATIVE MANAGEMENT: 10 kg partial weight bearing for 6-8 weeks. Limited range of motion 0-0-90 degrees for 6 weeks. RESULTS: In a period of 2 years, seven patients with posterolateral tibial plateau fractures received open reduction and internal fixation by using the modified posterolateral approach. The patients were examined at follow-up between 12 and 24 months after surgery. Six patients were free of pain with full range of motion and stable knee joints. Radiologically, a good fracture reduction was achieved in six cases. In one patient with a posterolateral comminuted dislocation fracture, a small fracture step and a gap could be observed. No approach-related complications were found. PMID- 20349176 TI - Predictors of outcomes of assertive outreach teams: a 3-year follow-up study in North East England. AB - INTRODUCTION: Assertive outreach (AO) is a required component of services for people with severe mental illness in England. However, the claims to its effectiveness have been contested and the relationships between team organisation, including model fidelity, the use of mental health interventions and outcomes for service users remain unclear. METHOD: Three-year follow up of 33 AO teams was conducted using standardised measures of model fidelity and mental health interventions, and of current location and a range of outcomes for service users (n = 628). Predictors of the number of hospital admissions, mental health and social functioning at T2, and discharge from the team as 'improved' were modelled using multivariate regression analyses. RESULTS: Teams had moderate mean ratings of fidelity to the AO model. All rated highly on the core intervention modalities of engagement, assessment and care co-ordination, but ratings for psychosocial interventions were comparatively low. Two-thirds (462) of service users were still in AO and data were returned on 400 (87%). There was evidence of small improvements in mental health and social functioning and a reduction in the mean number of hospital admissions in the previous 2 years (from 2.09 to 1.39). Poor outcomes were predicted variously by service users' characteristics, previous psychiatric history, poor collaboration with services, homelessness and dual diagnosis. Fidelity to the AO model did not emerge as a predictor of outcome, but the team working for extended hours was associated with more frequent in-patient admissions and less likelihood of discharge from AO. Supportive interventions in daily living, together with the team's use of family and psychological interventions were also associated with poorer outcomes. Possible explanations for these unexpected findings are considered. CONCLUSION: AO appears to have been quite successful in keeping users engaged over a substantial period and to have an impact in supporting many people to live in the community and to avoid the necessity of psychiatric hospital admission. However, teams should focus on those with a history of hospital admissions, who do not engage well with services and for whom outcomes are less good. Psychosocial interventions should be applied. The relationship between model fidelity, team organisation, mental health interventions and outcomes is not straightforward and deserves further study. PMID- 20349175 TI - [New trends in ultrasound diagnostics of carotid stenoses]. AB - The B-mode image quality of vessels has markedly increased with the advent of new transducer technologies. Morphological changes of the vessel wall, ulcerations, dissections or wall lesions benefit from non-Doppler dependent flow imaging methods. Two-dimensional imaging of the elasticity of the vessel wall may in future benefit from high speed imaging techniques. The biggest improvement in vessel imaging is probably the prudent use of contrast-enhanced ultrasound by which neovascularization can be visualized. Plaque vascularization is looked upon as an important risk factor in the evaluation of possible vulnerable plaques. PMID- 20349177 TI - Analytic model comparing the cost utility of TVT versus duloxetine in women with urinary stress incontinence. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to assess cost utility of duloxetine versus tension-free vaginal tape (TVT) as a second-line treatment for urinary stress incontinence. METHODS: A Markov model was used to compare the cost utility based on a 2-year follow-up period. Quality-adjusted life year (QALY) estimation was performed by assuming a disutility rate of 0.05. RESULTS: Under base-case assumptions, although duloxetine was a cheaper option, TVT gave a considerably higher QALY gain. When a longer follow-up period was considered, TVT had an incremental cost-effectiveness ratio (ICER) of pound 7,710 ($12,651) at 10 years. If the QALY gain from cure was 0.09, then the ICER for duloxetine and TVT would both fall within the indicative National Institute for Health and Clinical Excellence willingness to pay threshold at 2 years, but TVT would be the cost effective option having extended dominance over duloxetine. CONCLUSIONS: This model suggests that TVT is a cost-effective treatment for stress incontinence. PMID- 20349178 TI - Is the beneficial effect of antimuscarinics related to motor or sensory changes in the bladder? AB - INTRODUCTION AND HYPOTHESIS: The aim of the study was to assess the sensory and motor effects of antimuscarinic treatment on the bladder in women with overactive bladder, detrusor overactivity demonstrated on urodynamics and a mean bladder wall thickness (BWT) greater than 5 mm. METHODS: Fifty-eight women underwent treatment with antimuscarinics in 12 weeks. Before treatment and at 1, 2, 6 and 12 weeks of treatment, women completed the patient perception of bladder condition (PPBC) single-item global questionnaire, indicated the severity of their urgency on a visual analogue scale (VAS) and underwent transvaginal ultrasound to determine mean bladder wall thickness (BWT). RESULTS: PPBC and VAS scores for urgency declined throughout the treatment course whereas mean BWT declined during the first 6 weeks of treatment and then reached a plateau after falling to below 5 mm. CONCLUSION: The mechanism of action of antimuscarinics appears to be a complex interaction of sensory and motor components. PMID- 20349179 TI - Critical aspects of biointerface design and their impact on biosensor development. AB - The stable integration of a biological recognition element on a transducing substrate surface is the single most important step in the creation of a high functioning sensor surface. The key factors affecting biotic and abiotic functionalities at the biointerface are both chemical and physical. Understanding the interactions between biomolecules and surfaces, and their emergent complexity, is critical for biointerface implementation for sensing applications. In this overview, we highlight materials and methods typically used for biosensor development. Particular emphasis has been given to the experimental evaluation of biointerfacial properties and functionality. Promising research directions for application of biointerfaces to biosensing are suggested. PMID- 20349180 TI - Actin microfilament involved in regulation of pacemaking activity in cultured interstitial cells of Cajal from murine intestine. AB - The present study investigated the effect of actin microfilament structure on pacemaker currents and calcium oscillation in cultured murine intestinal interstitial cells of Cajal (ICCs) by whole-cell patch-clamp technique and calcium imaging technique. Cytochalasin B, a disruptor of actin microfilaments, decreased the amplitude and frequency of pacemaker currents from 491.32 +/- 160.33 pA and 11.73 +/- 0.79 cycles/min to 233.12 +/- 92.00 pA and 10.29 +/- 0.76 cycles/min. Cytochalasin B also decreased the amplitude and frequency of calcium oscillation from 0.32 +/- 0.08 (DeltaF/F0) and 2.75 +/- 0.17 cycles/min to 0.02 +/- 0.01 (DeltaF/F0) and 1.20 +/- 0.08 cycles/min. Phalloidin, a stabilizer of actin microfilaments, increased the amplitude and frequency of pacemaker currents from 751.79 +/- 282.82 pA and 13.93 +/- 1.00 cycles/min to 1234.34 +/- 607.83 pA and 14.68 +/- 1.00 cycles/min. Phalloidin also increased the amplitude and frequency of calcium oscillation from 0.26 +/- 0.01 (DeltaF/F0) and 2.27 +/- 0.18 cycles/min to 0.43 +/- 0.03 (DeltaF/F0) and 2.87 +/- 0.07 cycles/min. 2 Aminoethoxydiphenyl borane (2-APB), an IP(3) receptor blocker, suppressed both pacemaker currents and calcium oscillations. 2-APB also blocked the phalloidin induced increase in pacemaker currents and calcium oscillation. Ryanodine, an inhibitor of calcium-induced calcium release, did not affect pacemaker current but suppressed calcium oscillations. Ryanodine had no effect on altering phalloidin-induced increases in pacemaker current and calcium oscillation. These results suggest that actin microfilaments regulate pacemaker activity via the IP(3)-induced calcium release signaling pathway. PMID- 20349181 TI - Surface display of acid protease on the cells of Yarrowia lipolytica for milk clotting. AB - The acid protease structural gene was amplified from the genomic DNA of Saccharomycopsis fibuligera A11. When the gene was cloned into the multiple cloning site of the surface display vector pINA1317-YlCWP110 and expressed in the cells of Yarrowia lipolytica, the cells displaying the acid protease could form clear zone on the plate-containing milk indicating that they had extracellular acid protease activity. The cells displaying the acid protease can be used to effectively clot skimmed milk. The highest clotting milk activity (1,142.9 U/ml) was observed under the conditions of pH 3.0, 40 degrees C, 20 mM of CaCl(2), and 10% skimmed milk powder. We found that the acid protease displayed on the cells of Y. lipolytica which has generally regarded as safe status could be easily isolated and concentrated compared to the free acid protease. Therefore, the displayed acid protease may have many potential applications in food and cheese industries. This is the first report that the yeast cells displaying the acid protease were used to clot milk. PMID- 20349182 TI - Microbial community dynamics in anaerobic bioreactors and algal tanks treating piggery wastewater. AB - Integrated biosystem is becoming a major aspect of wastewater management practice. Microbial communities in piggery wastewater sampled from anaerobic (thermophilic and mesophilic) and aerobic digesters (algal tanks) during waste remediation were analyzed by culture-independent techniques based on polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). The use of Muyzer's 314F-GC, 518R bacterial primers, and archaeal A934F, 1309R primers followed by partial 16s rDNA sequence analysis of the main bands from DGGE revealed the presence of unknown and as yet uncultured microorganisms but also showed functional and ecologically significant denitrifying, acetogenic bacteria along with autotrophic, hydrogenotrophic, and acetoclastic methanogen archaea. Thermophilic digesters were dominated by gamma-Proteobacteria, Methanothermobacter sp., while mesophilic digesters showed dominance by Firmicutes, uncultured bacteria, Methanosarcina, and Methanoculleus genera. Under aerobic conditions within algal tanks, pH rose from 7.17 to 9.32, with a significant decrease in total ammonia nitrogen, chemical oxygen demand, and soluble phosphorus levels. PCR-DGGE proved a useful tool for investigating the dynamics of microbial community in the bio-processing of piggery wastewater. Knowledge of the microbial communities involved in digestion of piggery wastewater will allow optimization of integrated biosystem by removing the main pollutants like inorganic ammonium-nitrogen, phosphorus, and pathogens from intensive farming system. PMID- 20349183 TI - Biosynthesis and production of polysialic acids in bacteria. AB - Polysialic acids (PA) are protective capsular sialohomopolymers present in some bacteria which can invade the mammalian host and cause lethal bacteremia and meningitis. Biosynthesis and translocation of PA to the cell surface are equivalent in different species and bacterial strains which are produced. The diversity in PA structure is derived from the PA linkages and is a consequence of the specific sialyltransferase activities. The monomer acetylation and the polymer length could be important factors in the potential virulence. In vivo PA production is affected by different physical and chemical factors. The temperature of cellular growth strictly regulates PA genesis through a molecular complex and multifactorial mechanism that operate to transcription level. PMID- 20349184 TI - Occurrence, characteristics, and applications of fructosyl amine oxidases (amadoriases). AB - Amadori compounds, formed by the Maillard reaction between reducing sugars (e.g., glucose) and amines (e.g., lysine residues in proteins), are ubiquitous in nature and have been implicated in aging and several chronic diseases. Fructosyl amine oxidases (FAOXs) are a relatively new class of enzymes that cleave amadori compounds and have been found in fungi, yeast, and bacteria. This mini-review summarizes over a dozen of FAOXs with different substrate specificities have been isolated, characterized, and engineered to date. All known FAOX sequences except one have the consensus motif for the ADP-binding betaalphabeta-fold common to all FAD and NAD enzymes, and a recently solved crystal structure provides important clues for this class of enzymes. FAOXs have been explored for applications in diabetes diagnosis, detergents, and food processing. Given that naturally occurring FAOXs can only react directly with small glycated amino acids or short peptides, it is of great interest to engineer and expand the accessibility of the substrate binding sites of these enzymes. PMID- 20349185 TI - 18F-FDG PET/CT for monitoring induction chemotherapy in patients with primary inoperable penile carcinoma: first clinical results. AB - PURPOSE: The aim of this study was to explore the role of (18)F-FDG PET/CT for monitoring treatment response in patients with primary inoperable (i.e. advanced) penile carcinoma treated with induction chemotherapy and to compare the metabolic tumour response with the radiological evaluation provided by CT imaging. METHODS: Eight patients with advanced penile carcinoma were studied. All had undergone (18)F-FDG PET/CT imaging at baseline and after two cycles of induction chemotherapy. The metabolic tumour response was evaluated according to European Organisation for Research and Treatment of Cancer (EORTC) criteria for therapy response. The radiologic tumour response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Response evaluations were done separately and blinded for other patient data. For definition of the reference, all patients were rated as responders or non-responders by a multidisciplinary tumour board. RESULTS: PET/CT showed hypermetabolic uptake of FDG matching with malignancy in all eight patients. According to the reference, six patients were responders and two non-responders after two cycles of chemotherapy. The metabolic tumour response was considered accurate in all eight patients. In seven of the eight patients, the radiological tumour response was in agreement. In three patients correctly identified as responders, the radiological tumour response was deemed suboptimal compared with the metabolic assessment. Five of the six responders continued chemotherapy after response evaluation up to four cycles and were operated subsequently. Histopathological analysis confirmed the metabolic tumour response. CONCLUSION: (18)F-FDG PET/CT imaging is feasible for monitoring response in patients with advanced penile carcinoma treated with induction chemotherapy. Our preliminary results suggest that PET/CT is potentially more reliable than CT alone. PMID- 20349186 TI - Population-based epidemiological study of primary intracranial tumors in childhood. AB - OBJECT: Brain tumors are the most common solid tumors in children and their prognosis is poor. Epidemiologic data from a population-based cancer registry provide the information necessary to determine the incidence rate of pediatric brain tumors. The aim of this study was to determine the epidemiology of childhood primary intracranial tumors in Kumamoto Prefecture, Japan. METHODS: We surveyed 210 patients younger than 15 years who were diagnosed with primary intracranial tumors between 1989 and 2008; 159 (75.7%) of the tumors were confirmed microscopically. RESULTS: The age-adjusted annual incidence rate was 36.1 cases per million children. The boys/girls ratio was 1.31. The age-specific annual incidence rate was 28.5-, 40.9-, and 38.4 cases per million for the 0- to 4-, 5- to 9-, and 10- to 14-year age group, respectively. The incidence was highest in 10- to 14-year-old boys (53.6 per million) and lowest in 10- to 14 year-old girls (22.6 per million). The most common tumor was astrocytoma (35.7%) with an annual incidence rate of 13.2 per million, followed by germ cell tumor (14.3%, 5.0 per million), craniopharyngioma (10.5%, 3.8 per million), medulloblastoma (10.0%, 3.7 per million), and ependymoma (4.8%, 1.5 per million). The distribution of the tumor type varied with the patient age and gender. Although there were no germ cell tumors in 0- to 4-year-old boys, they were the second-most common tumor in 10- to 14-year-old boys. Conversely, while there were no medulloblastomas in 10- to 14-year-old girls, their incidence was high in 0- to 4-year-old girls. CONCLUSIONS: In this Kumamoto survey, the incidence rate of primary intracranial tumors in children was similar to that in Western countries. However, the incidence and relative frequency of particular histological types of childhood brain tumors such as germ cell tumors and craniopharyngiomas were different between Japan and Western countries. PMID- 20349187 TI - Preterm birth and neurodevelopmental outcome: a review. AB - BACKGROUND: The incidence of preterm delivery and the survival rate of preterm newborns are rising, due to the increased use of assisted reproductive technology associated with multiple gestations and improved technology in obstetrics and neonatology, which allow saving preterm infants at earlier gestational ages. As a consequence, the risk of developmental disabilities in preterm children is high, and clinical pictures need to be fully defined. METHODS: Narrative review including articles regarding neurodevelopmental disorders published in the international medical literature and reported in PubMed between the years 2000 and January 2010. RESULTS: Although survival rates of extremely low birth weight infants (ELBW) significantly increased during the last decade, the substantial stability of disability trends in this population was disappointing. Late-preterm infants, who account for about 75% of all preterm births and had not been considered at risk for adverse long-term neurodevelopmental outcomes in the past, are now reconsidered as more likely to develop such events, though their risk remains lower than in ELBW. CONCLUSIONS: The findings of the studies discussed in our article support the importance of early diagnosis in order to make decision about appropriate treatment of preterm infants. PMID- 20349188 TI - Trends in methadone-related deaths in Zurich. AB - Methadone has a long and successful history in the treatment of opioid addiction. In recent years, it has become popular again--as potent and inexpensive analgesic in patients with chronic pain. Since methadone has been used fatalities have been reported. In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of the past 10 years occurred during substitution programmes or illicit intake of methadone while only three of them could be attributed to methadone used as an analgesic. Noticeable in our study was the high percentage of cases of combined drug intoxication (76%). The most frequent co-intoxicants were alcohol and cocaine. Mortalities attributed to methadone intoxication alone were a rare finding and could only be detected in five cases of deceased who had received methadone maintenance treatment. The aim of our study is to assess the trends in the number and nature of methadone related fatalities in Zurich during the last 19 years. For this purpose a previous study from Zurich (1989-1997) was included, whereby a very long observation period and large number of cases resulted. PMID- 20349190 TI - The use of post-mortem computed tomography in the investigation of intentional neonatal upper airway obstruction: an illustrated case. AB - We present a single case report illustrating the diagnostic role of multi-slice computed tomography (MSCT) in the investigation of suspicious child death where mechanical asphyxia is suspected. The case illustrates how radiological findings that may not be observable on conventional plain X-ray were identified by post mortem MSCT. We illustrate how MSCT can illustrate the position of a foreign body within the upper airway of a neonate without the need for in situ dissection and how the combination of post-mortem MSCT with skeletal survey can provide enhanced diagnostic information in the investigation of not only whether the child was liveborn but also the consideration as to whether or not death has been caused by upper airway obstruction. PMID- 20349191 TI - Immunohistochemical expression of fibronectin in the lungs of fire victims proves intravital reaction in fatal burns. AB - Immunohistochemical studies about the presence of fibronectin in the lungs were performed in a group of 73 fire victims (63 cases of intravital and 10 cases of postmortem burn) as well as in an unselected control group of 55 individuals not exposed to fire before death. The cases of intravital burn showed a significantly stronger fibronectin expression than the control cases and the cases of postmortem burn. Fibronectin was mainly present in macrophages of the peribronchial lung parenchyma and, not associated with cells, in the matrix of peribronchial tissue. Our findings suggest that higher levels of fibronectin expression in the lung tissue of burn victims compared to fire-unrelated deaths may serve as an indicator of an early intravital inflammatory response to fire damage. PMID- 20349192 TI - Bestrophins and retinopathies. AB - Best vitelliform macular dystrophy (BVMD, also called Best's disease) is a dominantly inherited, juvenile-onset form of macular degeneration, which is characterized by abnormal accumulation of yellow pigment in the outer retina and a depressed electro-oculogram light peak (LP). Over 100 disease-causing mutations in human bestrophin-1 (hBest1) are closely linked to BVMD and several other retinopathies. However, the physiological role of hBest1 and the mechanisms of retinal pathology remain obscure partly because hBest1 has been described as a protein with multiple functions including a Ca2+-activated Cl- channel, a Ca2+ channel regulator, a volume-regulated Cl- channel, and a HCO3- channel. This review focuses on how dysfunction of hBest1 is related to the accumulation of yellow pigment and a decreased LP. The dysfunction of hBest1 as a HCO3- channel or a volume-regulated Cl- channel may be associated with defective regulation of the subretinal fluid or phagocytosis of photoreceptor outer segments by retinal pigment epithelium cells, which may lead to fluid and pigment accumulation. PMID- 20349193 TI - In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake. AB - AMP-activated protein kinase (AMPK) is expressed in the apical membrane of cortical thick ascending limb, distal, and collecting tubules as well as macula densa cells of the kidneys. AMPK is an active modulator of epithelial Na(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, and the ATP-dependent potassium channel. The present experiments explored whether AMPK participates in the regulation of tubuloglomerular feedback (TGF) and renal tubular sodium handling. To this end, renal clearance and micropuncture experiments were performed in anesthetized rats. Under normal NaCl diet, neither TGF response nor renal fluid and sodium excretion were altered by pharmacological activation of AMPK in vivo. However, under high NaCl diet, the TGF response was significantly enhanced after intravenous or intratubular application of the AMPK activator AICAR. Moreover, AICAR application significantly increased fractional delivery of fluid and sodium to the end of the proximal tubule. High dietary NaCl intake increased the renal transcript levels encoding the AMPK-alpha1 subunit, while it decreased the expression of AMPK-beta1 and AMPK-gamma2 subunits. Immunoblots revealed that high dietary NaCl intake reduced renal expression of activated AMPK by about three times compared to normal NaCl diet whereas additional AICAR application increased AMPK activity. Our results suggest that AMPK regulates tubuloglomerular balance as well as tubular transport upon change of renal work load. PMID- 20349194 TI - Effect of methanolic extract of Balanites aegyptiaca fruits on enteral and parenteral stages of Trichinella spiralis in rats. AB - There is a considerable interest in developing new anthelmintic drugs including those from medicinal plants due to increasing evidence of parasitic resistance against present anthelmintic drugs and decreasing activity against encapsulated larval stages of parasites. This study was carried out to assess, for the first time, the effectiveness of methanolic extract of Balanites aegyptiaca (BAE) fruits against different stages (pre-adult, migrating larvae, and encysted larvae) of Trichinella spiralis in rats compared with commonly used anthelmintic albendazole. Oral administration of BAE at a dose of 1,000 mg/kg b.wt. for five successive days throughout the parasite life cycle led to a marked reduction of migrating and encysted larval rate by 81.7% and 61.7%, respectively, in the muscular tissue. This treatment was less effective against adults in the gut (47.8%). Albendazole treatment at a dose of 10 mg/kg b.wt. for five successive days resulted in a marked eradication of T. spiralis adult worms (94.4%) and less reduction of migrating and encysted larval infections of skeletal muscles (62.2% and 26.4%, respectively). BAE-treated groups showed marked decreases in serum glucose levels, triglyceride concentrations, aspartate aminotransferase (AST), creatinine phosphokinase (CPK) activities, and lipid peroxide products (malondialdehyde, MDA) as well as an increase in glutathione level in both serum and muscular tissue compared to albendazole-treated- and infected-untreated groups. This result was confirmed by few numbers of living- and dead-encysted larvae and less destruction of the diaphragm and skeletal muscle tissues in BAE treated groups compared to other treated groups. It can be concluded that the methanolic extract of B. aegyptiaca fruits has high effectiveness against parenteral stages of T. spiralis than albendazole. Albendazole is more effective against enteral stage of T. spiralis than the extract. PMID- 20349195 TI - Renylaima capensis n. gen., n. sp. (Trematoda: Brachylaimidae) from the urinary system of the shrew Myosorex varius Smuts, 1832 (Insectivora: Soricidae). AB - A trematode species belonging to the family Brachylaimidae was found in the kidneys and ureters of the forest shrew Myosorex varius (Insectivora: Soricidae: Crocidosoricinae) in a restricted, very damp area of the Hottentots Holland Mountain range, near Cape Town, South Africa. The adult stage is described anatomically and histologically. The relative frequency of monotesticular forms is highlighted. A comparison is made with other brachylaimid species known to infect shrews and other peculiar brachylaimids from poikilothermic invertebrates and vertebrates with which the South African species shares several aspects. Peculiar characteristics such as absence of a cirrus pouch and cirrus and presence of a genital atrium that can be evaginated to produce a prominent ventral extention of the body, as well as the fact that the urinary system of a mammal host is an extraordinary microhabitat for a trematode, indicate that this digenean represents a new genus and species for which the name Renylaima capensis n. gen., n. sp. is proposed. PMID- 20349196 TI - Experimental infection with Ancylostoma ceylanicum in dogs and efficacy of a spot on combination containing imidacloprid 10% and moxidectin 2.5% (Advocate/Advantage Multi, Bayer Animal Health). AB - Ancylostoma ceylanicum is a common hookworm of dogs, cats and humans in Asia. More recently, this hookworm was found to infect dogs in Australia. The objective of this study was to determine the efficacy of a spot on combination product containing imidacloprid 10% and moxidectin 2.5% (Advocate/Advantage Multi, Bayer Animal Health) against A. ceylanicum in experimentally infected dogs. Twelve dogs were each subcutaneously injected with 300 infective third-stage larvae of A. ceylanicum. Pups were stratified by egg count and randomly allocated equally into control and treatment groups. The pups in the treatment group were each treated with a spot on combination of 10% (w/v) imidacloprid and 2.5% (w/v) moxidectin, administered topically at the skin surface between the shoulder blades. The dogs in the control group were not treated. Egg counts were performed daily until the end of the study period and compared for the treated and control groups. No eggs were detected in the treated group of pups within 4 days of treatment and faecal samples from this group remained negative throughout the rest of the study, resulting in a treatment efficacy (egg reduction) of 100% (P < 0.0001). The egg counts remained high (4,469 +/- 2,064 eggs per gram, epg) in the untreated control group for the rest of the study period. This study demonstrated that the spot on combination containing imidacloprid 10% and moxidectin 2.5 % (Advocate/Advantage Multi, Bayer Animal Health) given at the recommended dose is highly effective against infection with A. ceylanicum in dogs. PMID- 20349197 TI - A prospective cohort study of ALI/ARDS in the Tohoku district of Japan (second report). AB - PURPOSE: We previously reported a study of systemic inflammatory response syndrome (SIRS) cases in the Tohoku district of Japan in which the patients showed a 30-day mortality from acute lung injury/acute respiratory distress syndrome (ALI/ARDS) of about 20%. Cases in which chest X-ray findings did not meet ALI/ARDS criteria were diagnosed as acute hypoxemic respiratory failure (AHRF), but about 50% of these patients progressed to ALI/ARDS. The objective of this study was to verify the findings obtained in the earlier study and to gain further insights into the pathognomonic symptoms of AHRF associated with SIRS. METHODS: A prospective cohort study was performed in SIRS patients admitted to the intensive care unit (ICU) with PaO(2)/fractional inspired oxygen (FIO(2)) < or = 300 mmHg. Patients were assigned to ALI or ARDS groups based on symptoms at ICU entry. Cases in which chest X-ray showed no infiltration shadows in bilateral lung fields were classified as AHRF. RESULTS: A total of 240 patients were enrolled in the study. The 30-day mortalities were 21.6% and 20.0% in the ALI and ARDS groups, respectively. Of the 88 AHRF patients, 49 progressed to ALI/ARDS, with progression occurring within 3 days after ICU entry in most cases; 39 patients recovered with no progression. Chest X-ray and computed tomography (CT) showed no findings indicating ALI/ARDS in 20 AHRF patients at ICU entry, but 7 of these patients progressed to ALI/ARDS. CONCLUSION: The mortality rates of ALI and ARDS were 21.6% and 20.5%, respectively. More than half of the AHRF patients progressed to ALI or ARDS. Some AHRF patients had normal findings on chest CT, but subsequently showed a bilateral shadow on a chest X-ray. This indicates that mild pathologic lesions may not show imaging abnormalities. PMID- 20349198 TI - A case of lower-extremity deep burn wounds with periosteal necrosis successfully treated by use of allogenic cultured dermal substitute. AB - In patients with burns, bone exposure accompanies serious problems which occasionally lead to amputation. We present a case of an 82-year-old woman who sustained 22% of total body surface area flame burns on her bilateral lower extremities with bone exposure. Despite fascial excision and mesh skin graft, muscles, bones, and tendons were widely exposed on her right leg. The wound was infected by methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. To promote wound healing, we applied an allogeneic cultured dermal substitute (CDS) to the wound surface once weekly, resulting in healthy granulation except for the exposed bone area of the right anterior tibia. We then shaved the cortex of the exposed bone surface until bone marrow bleeding, and grafted mesh skin in combination with CDS. Finally, all wounds healed without osteomyelitis. The use of CDS to treat deep burns exposing bone surface may expand reconstructive options for extremities that otherwise might have been amputated. PMID- 20349199 TI - Extracorporeal membrane oxygenation as a "bridge to recovery" in a case of myotomy for myocardial bridge complicated by biventricular dysfunction. AB - The incidence of cardiac dysfunction after routine cardiac surgical procedures is quite high (3-5%), but the majority of patients improve using inotropic drugs or intraaortic balloon counterpulsation. However, approximately 1% of these patients do not benefit from using these supports, and they need more invasive strategies, such as ventricular assist devices. Extracorporeal membrane oxygenation (ECMO) is one of them, and it offers biventricular support, can be managed very easily and is one of the cheapest devices. We describe our experience with ECMO in a case of postocardiotomy failure after myotomy for myocardial bridge. Because of failure of medical therapy, we decided to perform surgical myotomy of the bridge and coronary artery bypass grafting of the LAD with the left internal mammary artery. Many episodes of ventricular fibrillation occurred with quick worsening of biventricular function requiring extracorporeal membrane oxygenation (ECMO) support. The pump flow was maintained at about 1.8-2 l/m(2) (about 80% of the ideal flow) in order to reduce cardiac work offering a more rapid recovery of cardiac function. ECMO support was slowly reduced because EKG progressively improved and the hemodynamic parameters were stable. ECMO was interrupted in the 4th postoperative day when mean pressure was >90 mmHg and organ perfusion was adequate. The particularity of our case was the complicated management of MB: it is very uncommon that myotomy of the LAD results in biventricular dysfunction. Our experience confirms that benign pathologies such as MB may hide life threatening complications and that ECMO support is the simplest solution in case of biventricular dysfunction. PMID- 20349200 TI - Performance of rapid influenza testing in hospitalized children. AB - Influenza infection is associated with high hospitalization rates among young children. Rapid diagnosis of influenza infection is particularly useful in order to prevent nosocomial infection and allows for the timely initiation of antiviral treatment. We evaluated the performance of a rapid influenza test in hospitalized children during the influenza season. All children (aged 6 months to 14 years) hospitalized with fever and/or respiratory symptoms, admitted during the 2005 influenza season, participated in the study. A multiplex reverse transcriptase polymerase chain reaction (RT-PCR), able to identify IFV-A H1N1, H3N2, and IFV-B subtypes, was performed on nasopharyngeal aspirates. The nasal swab was tested with a lateral-flow immunoassay (QuickVue Influenza Test). The performance of the rapid test was compared with the results of PCR. Influenza infection was diagnosed by PCR in 41/217 (19%) patients. Infection with influenza A virus (H3N2) was diagnosed in all cases. The performance of the QuickVue Influenza Test was estimated as follows: sensitivity 67.5%, specificity 96%, positive predictive value 79%, and negative predictive value 93%. The sensitivity of the test was higher in infants aged 6-12 months, in those with short duration of symptoms, and in the peak phase of the epidemic. The QuickVue Influenza Test is useful and reasonably accurate to detect influenza infection in hospitalized children during the influenza season. Infection with influenza virus is unlikely if the test is negative. A positive result suggests that infection is probable if influenza virus circulates in the community. PMID- 20349201 TI - Migraine treatment in developmental age: guidelines update. AB - There is a serious lack of controlled studies on the pharmacological treatment of primary migraine in the developmental age; there is, consequently, an urgent need for new, evidence-based approaches to this long-neglected field of research. Moreover, previous studies have stated that the placebo response is greater in pediatric patients than in adults and that a reduction in the attack frequency in the absence of any pharmacological treatment is observed more frequently in pediatric migraine patients than in adults. Besides these preliminary considerations, the shorter duration of migraine attacks and other characteristic semeiological features of the clinical picture in children are such that the design of randomized controlled trial (RCT) is more problematic in the developmental age than in the adult. Bearing in mind all these weak points, the aim of this review was to summarize and update recent guidelines for the treatment of primary migraine in children and adolescents. The most recent guidelines are those published by the Italian Society for the study of Headache, the French Society for the study of Migraine and Headache, and the American Academy of Neurology. We have incorporated into these guidelines the results from the few, recent RCTs, clinical controlled trials, open-label studies, meta analyses and reviews that have been published since 2004; owing to the lack of strong evidence in this field of research, we have sometimes even mentioned pilot non-controlled studies, case series and expert opinions. Lastly, evidence was classified and the recommendations were categorized according to different levels. PMID- 20349202 TI - Socio-economic differences in the use of dairy fat in Russian and Finnish Karelia, 1994-2004. AB - OBJECTIVES: To determine socio-economic differences from 1994 to 2004 in the use of butter and milk in Pitkaranta in the Republic of Karelia, Russia and North Karelia, Finland. METHODS: Health behaviour surveys in Pitkaranta (n = 3,599) and North Karelia (n = 3,652) in 1994, 1996, 1998, 2000 and 2004. RESULTS: A clear overall decrease occurred in the use of butter in cooking in Pitkaranta from 1994 to 2004. In both areas, subjects with lower education used butter in cooking and drank fat-containing milk more often. Regarding butter on bread, the educational patterns in the two areas were opposite: in Pitkaranta, subjects with lower education used butter less often but in North Karelia, they used butter on bread more often. Practically, no changes in socio-economic differences from 1994 to 2004 were observed in either area. CONCLUSIONS: The socio-economic differences in the use of dairy fat were stable in both areas but larger in North Karelia than in Pitkaranta. Our results support earlier assumptions of a weaker role of education as a determinant of health in Russia than in the western societies. PMID- 20349204 TI - Exposure to lanthanum compound diminishes LPS-induced inflammation-associated gene expression: involvements of PKC and NF-kappaB signaling pathways. AB - Lanthanum chloride, a rare earth compound, possesses antibacterial and cellular immunity regulating properties. However, the underlying molecular mechanisms remain largely unknown. In this study, we examined the effects of lanthanum chloride on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the expression of inducible NO synthase (iNOS) and TNF-alpha in RAW 264.7 cells, a mouse macrophage cell line. We found that the LPS-elicited excessive production of NO and TNF-alpha in RAW 264.7 cells was inhibited significantly in the presence of lanthanum chloride, and the attenuation of iNOS and TNF-alpha occurred at mRNA level. Furthermore, the possible signaling components affected by lanthanum chloride in the pathway that lead to LPS-induced iNOS and TNF-alpha expression were explored. The results indicated the involvements of PKC/Ca(2+) and NF-kappaB in the attenuation of NO and pro inflammatory cytokine production by lanthanum chloride. Our observations suggest a possible therapeutic application of this agent for treating inflammatory diseases. PMID- 20349203 TI - Deactivation of the rod response in retinopathy of prematurity. AB - It is known that retinopathy of prematurity (ROP) alters the activation of rod photoreceptors, but the effect of ROP on deactivation has not been investigated. We studied deactivation using an electroretinographic (ERG) paired flash procedure in 22 subjects (12 infants and 10 older subjects) with a history of preterm birth and ROP. The amplitude of the rod-isolated a-wave response to a flash presented 2-120 s after a test flash was measured, and the time at which it reached 50% of the single flash amplitude (t(50)) was determined by linear interpolation. Deactivation results were compared to those in former preterms who never had ROP (n = 6) and term-born controls. In infants, t(50) values of ROP subjects did not differ from those in subjects who never had ROP or term-born controls. Among mature ROP subjects, eight of 12 had t(50) values longer than any control subject. Prolonged deactivation in these mature ROP subjects may indicate lack of maturation of the deactivation process (t(50)) or progressive compromise of retinal function with increasing age. PMID- 20349205 TI - Purification and characterization of a liver-derived beta-N-Acetylhexosaminidase from marine mammal Sotalia fluviatilis. AB - A beta-N-Acetylhexosaminidase (EC 3.2.1.52) was purified from hepatic extracts of Sotalia fluviatilis, order Cetacea. The protein was purified by using ammonium sulfate fractionation and four subsequent chromatographies (Biogel A 1.5 m, Chitin, Deae-Biogel and hydroxyapatite resins). After these purification steps, the enzyme was purified 380.5-fold with an 8.4% yield. The molecular mass (10 kDa) was estimated by SDS-PAGE and MALDI-TOF analysis. A Km of 2.72 mM and Vmax 9.5 x 10(-6) micromol/(min x mg) were found for this enzyme, determined by p nitrophenyl-beta-D: -hexosaminide substrate digestion. Optimal pH and temperature for beta-N-Acetylhexosaminidase activity were 5.0 and 60 degrees C, respectively. Enzyme activity was inhibited by sodium selenate (Na(2)SeO(4)), mercuric chloride (HgCl(2)) and sodium dodecyl sulfate (C(12)H(25)SO(4)Na), and activated by zinc, calcium, barium and lithium ions. Characterization of the beta-N Acetylhexosaminidase in Sotalia fluviatilis can be a basis for physiological studies in this species. PMID- 20349206 TI - Inflammation and colorectal cancer: does aspirin affect the interaction between cancer and immune cells? AB - The effect of aspirin on colon-cancer-cell-induced cytokine secretion by peripheral blood mononuclear cells (PBMC) was examined. Aspirin was added to human colon cancer cells (HT-29 and RKO) or to PBMC incubated separately or jointly. The secretion of IFNgamma, IL-6, and IL-10 induced by HT-29 cells was decreased, that of IL-1beta was slightly increased, whereas IL-1ra production was not affected. With RKO cells, aspirin reduced IL-6, IL-1ra, and IL-10 synthesis and enhanced IFNgamma secretion, while IL-1beta remained unchanged. Conditioned media from colon cancer cells incubated without or with aspirin stimulated cytokine productions by PBMC similarly, suggesting that aspirin acts on the cell to-cell interaction between cancer cells and PBMC. The results indicate that aspirin alter the balance between pro- and anti-inflammatory cytokines generated by interaction between colon cancer and immune cells disclosing an additional role of the drug in affecting inflammation-induced colon cancer. PMID- 20349207 TI - Effects of gender and psychosocial factors on "friends with benefits" relationships among young adults. AB - Friends with benefits relationships (FWB) are a blend of friendship and physical intimacy outside of a committed romantic relationship. This study examined young adults' (n = 889) engagement in, and reactions to, a FWB relationship in the past year based on their gender, psychological distress, alcohol use, and relationship attitudes. Men (54.3%) were more likely than women (42.9%) to report at least one FWB relationship and both men and women reported that FWB relationships were associated with more positive emotional reactions than negative ones although this difference was larger for men. Greater alcohol use was related to engaging in a FWB relationship and this relationship was stronger for women. Further, thoughtfulness about relationship decisions moderated the relationship between alcohol use and engaging in FWB relationships, and again this moderation effect was stronger for women than men. Young adults with more psychological distress and who felt constrained in the FWB relationship were more likely to report negative emotional reactions. Implications for psychoeducational programs and future research are offered. PMID- 20349208 TI - The role of sex guilt in the relationship between culture and women's sexual desire. AB - A large body of literature demonstrates that East Asian women report lower sexual desire than Caucasian women. Although most studies have explained these differences by referring to general culture-linked differences in sexual conservatism, none have examined the potential role of specific constructs such as sex guilt. The goals of the current study were to examine the supposition that sexual conservatism mediates the relationship between culture and sexual desire, and to explore the potential mediating role of sex guilt in the link between culture and sexual desire. Caucasian (n = 105) and East Asian (n = 137) female university students completed questionnaires online. Caucasian women reported significantly higher levels of sexual desire, significantly lower levels of sexual conservatism, and significantly less sex guilt. In the entire sample, sexual conservatism and sex guilt separately mediated the relationship between ethnicity and sexual desire such that women with more sex guilt and those who were more sexually conservative reported lower sexual desire. Among the East Asian women, sex guilt, but not sexual conservatism, mediated the relationship between mainstream acculturation (degree of westernization) and sexual desire such that women with more sex guilt reported lower sexual desire. These findings suggest that sex guilt may be one mechanism by which ethnic groups differ in sexual desire. PMID- 20349209 TI - Bayesian semiparametric modeling for stochastic precedence, with applications in epidemiology and survival analysis. AB - We propose a prior probability model for two distributions that are ordered according to a stochastic precedence constraint, a weaker restriction than the more commonly utilized stochastic order constraint. The modeling approach is based on structured Dirichlet process mixtures of normal distributions. Full inference for functionals of the stochastic precedence constrained mixture distributions is obtained through a Markov chain Monte Carlo posterior simulation method. A motivating application involves study of the discriminatory ability of continuous diagnostic tests in epidemiologic research. Here, stochastic precedence provides a natural restriction for the distributions of test scores corresponding to the non-infected and infected groups. Inference under the model is illustrated with data from a diagnostic test for Johne's disease in dairy cattle. We also apply the methodology to the comparison of survival distributions associated with two distinct conditions, and illustrate with analysis of data on survival time after bone marrow transplantation for treatment of leukemia. PMID- 20349210 TI - Membrane proteome of the green sulfur bacterium Chlorobium tepidum (syn. Chlorobaculum tepidum) analyzed by gel-based and gel-free methods. AB - Chlorobium tepidum is a Gram-negative bacterium of the green sulfur phylum (Chlorobia). Chlorobia are obligate anaerobic photolithoautotrophs that are widely distributed in aquatic environments where anoxic layers containing reduced sulfur compounds are exposed to light. The envelope of C. tepidum is a complex organelle composed of the outer membrane, the periplasm-peptidoglycan layer, and the cytoplasmic membrane. In addition to the outer and plasma membranes, C. tepidum contains chlorosomes attached to the cytoplasmic side of the plasma membrane. Each cellular compartment has a unique set of proteins, called sub proteome. An important aim of proteome analysis is to study the level of the expressed genes and their response to environmental changes. Membrane protein studies are of primary importance to understand how nutrients are transported inside the cell, how toxic molecules are exported, and the mechanisms of photosynthesis and energy metabolism. PMID- 20349211 TI - Diabetes and its impact on health-related quality of life: a life table analysis. AB - PURPOSE: To investigate the health burden of diabetes and determine its impact on health-related quality of life (HRQOL) in a population with a high prevalence of chronic conditions. METHODS: A representative sample of the Canadian province of Newfoundland and Labrador (NL) was used to estimate prevalence of diabetes and mean health utility index (HUI), a utility-based measure of HRQOL. Diabetes deleted life expectancy (LE) and health-adjusted life expectancy (HALE) were derived to measure HRQOL. RESULTS: Diabetic individuals comprised 6.8% of the sample and accounted for 14% of total deaths from 2001 to 2005. Life Expectancy at age 15 was 61.3 years for men and 66.7 years for women, of which 53.0 and 57.0 years, respectively, were spent with perfect health (86.4 and 85.5%). Eliminating diabetes would extend both the overall LE and HALE for men by 1.3 and 1.4 years, and women by 2.0 and 1.7 years, respectively. People with diabetes had a significantly lower HRQOL than people without diabetes (mean HUI: 0.78 vs. 0.88, P < 0.01). CONCLUSION: The burden of illness from diabetes in NL is considerable. Using cause-eliminated LE and HALE provides a robust approach for assessing HRQOL that may have important implications for diabetes surveillance, prevention, and management strategies. PMID- 20349212 TI - Neck pain patients' preference scores for their current health. AB - PURPOSE: To elicit neck pain (NP) patients' preference scores for their current health, and investigate the association between their scores and NP disability. METHODS: Rating scale scores (RSs) and standard gamble scores (SGs) for current health were elicited from chronic NP patients (n=104) and patients with NP following a motor vehicle accident (n=116). Patients were stratified into Von Korff Pain Grades: Grade I (low-intensity pain, few activity limitations); Grade II (high-intensity pain, few activity limitations); Grade III (pain with high disability levels, moderate activity limitations); and Grade IV (pain with high disability levels, several activity limitations). Multivariable regression quantified the association between preference scores and NP disability. RESULTS: Mean SGs and RSs were as follows: Grade I patients: 0.81, 0.76; Grade II: 0.70, 0.60; Grade III: 0.64, 0.44; Grade IV: 0.57, 0.39. The association between preference scores and NP disability depended on type of NP and preference elicitation method. Chronic NP patients' scores were more strongly associated with depressive symptoms than with NP disability. In both samples, NP disability explained little more than random variance in SGs, and up to 51% of variance in RSs. CONCLUSION: Health-related quality-of-life is considerably diminished in NP patients. Depressive symptoms and preference-elicitation methods influence preference scores that NP patients assign to their health. PMID- 20349213 TI - Risk stratification for early esophageal adenocarcinoma: analysis of lymphatic spread and prognostic factors. AB - BACKGROUND: Knowledge of factors related to outcome is vital for the selection of therapeutic alternatives for patients with early (T1) esophageal adenocarcinoma. This study was undertaken to determine predictors of lymphatic spread and prognostic factors for T1 esophageal adenocarcinoma following esophagectomy. MATERIALS AND METHODS: A prospectively maintained database identified 85 patients with T1 esophageal adenocarcinoma who underwent esophagectomy without neoadjuvant therapy. Depth of tumor invasion (T stage) was subdivided into mucosal (T1a) or submucosal invasion (T1b). Median follow-up was 59 months. RESULTS: Thoracoscopically assisted 3-phase esophagectomy was performed in 73 of 85 patients (86%). Lymph node metastases (N stage) were identified in 9 of 85 patients (11%). Depth of tumor invasion (T stage), lymphovascular invasion (LVI), and poor differentiation were associated with N stage. The patients could be stratified into 4 risk groups for lymph node metastases: group I--T1a (0 of 35 patients [0%] with positive nodes); group II--T1b, well/moderate differentiation and no LVI (1 of 28 patients [4%] with positive nodes); group III--T1b, poor differentiation and no LVI (2 of 9 patients [22%] with positive nodes); and group IV--T1b any grade with LVI (6 of 13 patients [46%] with positive nodes). Survival analyses found T stage, N stage, LVI, and poor differentiation to be significant prognostic factors. CONCLUSIONS: Risk stratification is possible for patents with T1 esophageal adenocarcinoma. Local resection techniques without lymphadenectomy may be alternatives for T1a tumors. Esophagectomy should remain the standard of care for patients with T1b tumors and those with LVI or poor differentiation considered for neoadjuvant therapy. PMID- 20349214 TI - Establishment and characterization of human embryonic stem cell lines, Turkey perspectives. AB - Human embryonic stem cells (hESC), which are derived from the inner cell mass (ICM) of blastocyst stage embryos, are of great importance because of their unpredictable two unique features: their differentiation ability into all types of cells derived from three germ layers and their potentially unlimited capacity of self renewing with stable karyotype. These distinguished properties make hESC very promising cell source for regenerative medicine, tissue replacement therapies, and drug screening studies as well as genomics. However, due to the several technical problems, such as risk of teratoma formation, immune response, and unknown genetic pathways for lineage specific differentiation, and ethical drawbacks of their using in clinical treatments, hESC researches are still waiting to advance beyond to animal trials and drug studies. During the last decade, more than 300 new hESC lines have been derived and published by researchers worldwide. However, despite their similar well-known unique properties, recent studies reported that hESC lines have very individual properties and are differed from each other with regards to their differentiation ability and gene expression profiles. Therefore, all hESC lines should be characterized in detail and then registered in a stem cell bank for generating global database. In this report, the characteristic of hESC lines, which were established in Istanbul Memorial Hospital between 2003 and 2005, and derivation methods were described in detail to inform researchers and to facilitate new prospective cooperative studies. PMID- 20349215 TI - Relationships between levels of CXCR4 and VEGF and blood-borne metastasis and survival in patients with osteosarcoma. AB - The present study was designed to determine whether the expression of chemokine receptor CXCR4 and vascular endothelial growth factor (VEGF) is correlated with the extent of metastasis and the survival of patients with osteosarcoma. Using tissue microarrays, we analyzed the expression of CXCR4 and VEGF in tumor tissues collected from 56 patients with osteosarcoma. A two-year follow-up was performed to evaluate tumor metastatic behavior and the overall survival of the patients. There was a significant correlation between the expression of CXCR4 and the expression of VEGF in tumor tissues of these patients (P = 0.002). Univariate analysis revealed that expression of these proteins was correlated with clinical stage, but not age, gender, or serum alkaline phosphatase levels. The patients with tumors expressing CXCR4 and VEGF had worse overall survival rates compared with the patients with tumors that did not express CXCR4 (P = 0.03) or VEGF (P = 0.04). These data indicate that CXCR4 and VEGF expression is highly correlated with metastatic progression in patients with osteosarcoma and had predictive value for the metastasis and survival of osteosarcoma patients. PMID- 20349216 TI - Lack of significant association between TGF-beta1-590C/T polymorphism and breast cancer risk: a meta-analysis. AB - Transforming growth factor beta1 (TGF-beta1) is a cytokine that plays an important role in the control of cell proliferation and differentiation in breast cancer. The -509C/T polymorphism in the TGF-beta1 gene has been implicated in breast cancer risk. However, studies on the association between this polymorphism and breast cancer risk have produced conflicting results. To derive a more precise estimation of the relationship, a meta-analysis of the -509C/T polymorphism (5,825 cases and 7,953 controls) from seven published case-control studies was performed. Our analysis suggests that -509C/T has no association with breast cancer risk when using either dominant [odds ratio (OR) = 1.01, 95% confidence intervals (CI): 0.82-1.24], or recessive models (OR = 0.91, 95% CI: 0.66-1.27), or other genetic models to analyze the data. In ethnic subgroups analysis, -509C/T also did not appear to be a risk factor for breast cancer. However, larger scale primary studies are still required to further evaluate the interaction of TGF-beta1 -509C/T polymorphism and breast cancer risk in specific populations. PMID- 20349217 TI - Neurodynamics of mind: the arrow illusion of conscious intentionality as downward causation. AB - In cognitive neuroscience, the reissue of the notion of emergence and downward causation has been used as an interlevel model of mind-brain interactions from different perspectives. Within this perspective, intentionality has been interpreted as global to local determination (downward causation) on the neurophysiological level. Consciousness would act as the large-scale, global activity of the system that governs or constrains local interactions of neurons. This argument seems to solve several difficulties with regard to descriptions of consciousness on a neurophysiological and mental level. Nevertheless, the inconsistencies of this argument are shown, and a contextual and pragmatic explanation of the downward causation of consciousness is given. PMID- 20349218 TI - [Resurgence of yellow fever epidemics in Cote-d'Ivoire]. AB - Resurgence of yellow fever epidemics in Coted'Ivoire remains a major problem of public health. To describe this disease through the early alarm system of National Institute of Public Hygiene (NIPH) is convenient to us. This is a cross sectional study with descriptive aiming, which proceeded with epidemiological surveillance service of NIPH. The data were collected over 7 years (from 2001 to 2007), starting from the cards of notification, reports, and registers of the service. The main findings of our study are that: 1) we listed 1468 suspect cases including 41 confirmed and the lethality rate was 17.07% among the confirmed cases; 2) most cases of yellow fever were recorded between the years 2001 and 2007; 3) confirmed cases of yellow fever were above 15 years old in 83% of cases. This could be explained by absence of immunization during this age period; 4) recrudescence of cases was observed during the rainy season (June-July and September-October) and the principal vector was Aedes aegypti; 5) data analysis revealed a mean level of 79% for completude and 57%for promptitude of notification; these rates are inferior to WHO norms and; 6) average time of vaccine response post-epidemic was 31 days. Late response is due to difficulties in supplying vaccines. Reinforcement of epidemiological surveillance, prevention by mass immunization, and measurements of hygiene and cleansing are essential to slow down the evolution of this disease. PMID- 20349219 TI - Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. AB - Recently, the detection of occult cancer cells in peripheral blood has received a great deal of attention regarding the prediction of postoperative cancer recurrence and for novel strategies of adjuvant therapy. The aim of this study was to establish a new molecular diagnostic method of detecting circulating tumor cells. Gastric cancer SGC-7901 cells in 2 ml blood from healthy volunteers were serially diluted. Additional peripheral blood samples were collected from 90 patients and 27 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the levels of microRNA-106a (miR-106a) and microRNA-17 (miR-17). Receiver operating characteristics (ROC) curves were constructed. In recovery experiments, a significant correlation between the number of cancer cells and the levels of both miR-106a (r = -0.906, p = 0.037) and miR-17 (r = -0.912, p = 0.031) was found. In preoperative and postoperative patient groups, miR-106a and miR-17 levels were significantly higher than those in controls. The areas under the ROC curve for miR-106a, miR-17, and combination were 0.684 (p = 0.0066), 0.743 (p = 0.0001), and 0.741 (p = 0.0002), respectively. Our results indicate that the detection of miRNA in peripheral blood may be a novel tool for monitoring circulating tumor cells in patients with gastric cancers. PMID- 20349220 TI - Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects. AB - The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone. PMID- 20349221 TI - [Bipolar depression. Epidemiology, etiopathogenesis, and course]. AB - Bipolar disorder is one of the most frequent and severe mental disorders. A generally recurrent or chronic course is often predominated by bipolar depression. Genetic, neurobiological, and psychosocial factors are supposed to be relevant in the pathophysiology of this disorder. Current data have implicated dysfunction of neurotransmitter, neuroendocrine, and intracellular signaling networks. Neuroanatomic changes in bipolar disorder have been reported, too. In this article, we describe current knowledge regarding epidemiology, etiopathogenesis, and course of bipolar disorder with a focus on depression of bipolar disorder. PMID- 20349222 TI - Sustained production of spliced X-box binding protein 1 (XBP1) induces pancreatic beta cell dysfunction and apoptosis. AB - AIMS/HYPOTHESIS: Pro-inflammatory cytokines involved in the pathogenesis of type 1 diabetes deplete endoplasmic reticulum (ER) Ca2+ stores, leading to ER-stress and beta cell apoptosis. However, the cytokine-induced ER-stress response in beta cells is atypical and characterised by induction of the pro-apoptotic PKR-like ER kinase (PERK)-C/EBP homologous protein (CHOP) branch of the unfolded protein response, but defective X-box binding protein 1 (XBP1) splicing and activating transcription factor 6 activation. The purpose of this study was to overexpress spliced/active Xbp1 (XBP1s) to increase beta cell resistance to cytokine-induced ER-stress and apoptosis. METHODS: Xbp1s was overexpressed using adenoviruses and knocked down using small interference RNA in rat islet cells. In selected experiments, Xbp1 was also knocked down in FACS-purified rat beta cells and rat fibroblasts. Expression and production of XBP1s and key downstream genes and proteins was measured and beta cell function and viability were evaluated. RESULTS: Adenoviral-mediated overproduction of Xbp1s resulted in increased XBP1 activity and induction of several XBP1s target genes. Surprisingly, XBP1s overexpression impaired glucose-stimulated insulin secretion and increased beta cell apoptosis, whereas it protected fibroblasts against cell death induced by ER stress. mRNA expression of Pdx1 and Mafa was inhibited in cells overproducing XBP1s, leading to decreased insulin expression. XBP1s knockdown partially restored cytokine/ER-stress-driven insulin and Pdx1 inhibition but had no effect on cytokine-induced ER-stress and apoptosis. CONCLUSIONS/INTERPRETATION: XBP1 has a distinct inhibitory role in beta cell as compared with other cell types. Prolonged XBP1s production hampers beta cell function via inhibition of insulin, Pdx1 and Mafa expression, eventually leading to beta cell apoptosis. PMID- 20349223 TI - Deficiency of Atf3, an adaptive-response gene, protects islets and ameliorates inflammation in a syngeneic mouse transplantation model. AB - AIMS/HYPOTHESIS: Islet transplantation is a potential therapeutic option for type 1 diabetes. However, the need for multiple donors per patient and heavy immunosuppression of the recipients limit its use. The goal of this study was to test whether the gene encoding activating transcription factor 3 (ATF3), a stress inducible pro-apoptotic gene, plays a role in graft rejection in islet transplantation. METHODS: We compared wild-type (WT) and Atf3 knockout (KO) islets in vitro using stress paradigms relevant to islet transplantation: isolation, inflammation and hypoxia. We also compared the WT and KO islets in vivo using a syngeneic mouse transplantation model. RESULTS: ATF3 was induced in all three stress paradigms and played a deleterious role in islet survival, as evidenced by the lower viability of WT islets compared with KO islets. ATF3 upregulated various downstream target genes in a stress-dependent manner. These target genes can be classified into two functional groups: (1) apoptosis (Noxa [also known as Pmaip1] and Bnip3), and (2) immunomodulation (Tnfalpha [also known as Tnf], Il-1beta [also known as Il1b], Il-6 [also known as Il6] and Ccl2 [also known as Mcp-1]). In vivo, Atf3 KO islets performed better than WT islets after transplantation, as evidenced by better glucose homeostasis in the recipients and the reduction of the following variables in the KO grafts: caspase 3 activation, macrophage infiltration and expression of the above apoptotic and immunomodulatory genes. CONCLUSIONS/INTERPRETATION: ATF3 plays a role in islet graft rejection by contributing to islet cell death and inflammatory responses at the graft sites. Silencing the ATF3 gene may provide therapeutic benefits in islet transplantation. PMID- 20349224 TI - Engineering a subcellular targetable, red-emitting, and ratiometric fluorescent probe for Ca2+ and its bioimaging applications. AB - A new, visible-light-excited and red-emitting fluorescent Ca(2+) probe, STDBT, was synthesized, which consists of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N' tetraacetic acid as a Ca(2+)-chelating moiety and two benzothiazolium hemicyanine dyes as fluorophores. The spectral profiles of its free and Ca(2+)-bound forms were studied. Upon addition of Ca(2+), the fluorescence spectra of STDBT displayed a significant enhancement (about 48-fold) in fluorescence intensity and a 20-nm blueshift (from 600 to 580 nm) in the emission spectrum. Both the absorption and the excitation spectra of STDBT showed a very large (more than 100 nm) hypsochromic shift in the long-wavelength maxima upon binding with Ca(2+). Interestingly, in contrast with the commonly used Ca(2+) indicator Fluo-3, when the acetoxymethyl ester of STDBT enters into cells, it distributes both in the cytosol and the nucleus, but displays a very clear boundary between the two compartments. This allows STDBT to be used as a double targetable Ca(2+) probe that can be used to report cytoplasmic Ca(2+) and nuclear Ca(2+) simultaneously. PMID- 20349225 TI - Pyridinium aldoxime analysis by HPLC: the method for studies on pharmacokinetics and stability. AB - Reversed-phase separation of various pyridinium aldoximes requires a certain concentration of ion-pairing agent, as their chemical structures contain two quaternary amines in the pyridinium ring. Adequate mobile phase is scouted on the basis of retention of pyridinium aldoxime (using the graph of k' versus concentration of an ion-pairing agent) compared to the chromatogram of the background peaks originated from the homogenate. Change in the ion-pairing agent concentration was more expressed for the elution of K-203 than that of the background peaks from the serum, brain and cerebrospinal fluid. Stability of K 203 was investigated using HPLC. Determination of K-203 in tissue samples requires homogenization using either trichloroacetic acid or perchloric acid. Fast degradation takes place at acidic pH. Adjusting pH to neutral in the possible shortest time frame helps to avoid degradation. Degradation of K-203 was easily followed by HPLC separation and monitoring the elution with an ultraviolet absorbance detector at 276 nm. Amperometric detection indicates only the decrease of K-203 content. PMID- 20349226 TI - Determination of beta-glucosidase activity in soils with a bioanalytical sensor modified with multiwalled carbon nanotubes. AB - Soil microorganisms and enzymes are the primary mediators of soil biological processes, including organic matter degradation, mineralization, and nutrient recycling. They play an important role in maintaining soil ecosystem quality and functional diversity. Moreover, enzyme activities can provide an indication of quantitative changes in soil organic matter. Beta-glucosidase (beta-Glu) activity has been found to be sensitive to soil management and has been proposed as a soil quality indicator because it provides an early indication of changes in organic matter status and its turnover. The aims of the present study were to test and use a simple and convenient procedure for the assay of beta-Glu activity in agricultural soil. The method described here is based on the enzymatic degradation of cellobiose by beta-Glu present in the soil sample and the subsequent determination of glucose produced by the enzymatic reaction using screen-printed carbon electrodes modified with multiwalled carbon nanotubes (SPCE CNT) equipped with coimmobilized glucose oxidase and horseradish peroxidase enzymes. The potential applied to the SPCE-CNT detection was -0.15 V versus a Ag/AgCl pseudo-reference electrode. A linear calibration curve was obtained in the range 2.7-11.3 mM with a correlation coefficient. In the present study, an easy and effective SPCE-CNT-modified electrode allowed an improved amperometric response to be achieved and this is attributed to the increased surface area upon electrode modification. PMID- 20349227 TI - Optical recognition of salivary proteins by use of molecularly imprinted poly(ethylene-co-vinyl alcohol)/quantum dot composite nanoparticles. AB - Molecularly imprinted polymers (MIPs) have long been studied for applications in biomolecule recognition and binding; compared with natural antibodies, they may offer advantages in cost and stability. We report on the development of MIPs that "self-report" concentrations of bound analytes via fluorescence changes in embedded quantum dots (QDots). Composite QDot/MIPs were prepared using phase inversion of poly(ethylene-co-vinyl alcohol) (EVAL) solutions with various ethylene mole ratios in the presence of salivary target molecules (e.g. amylase, lipase, and lysozyme). These major protein components of saliva have been implicated as possible biomarkers for pancreatic cancer. The optimum (highest imprinting effectiveness) ethylene mole ratios of the commercially available EVALs were found to be 32, 38, and 44 mol% for the imprinting of amylase, lipase, and lysozyme, respectively. QD fluorescence quenching was observed on binding of analytes to composite MIPs in a concentration-dependent manner, and was used to construct calibration curves. Finally, the composite MIP particles were used for the quantitative detection of amylase, lipase, and lysozyme in real samples (saliva) and compared with a commercial Architect ci 8200 chemical analysis system. PMID- 20349228 TI - 3D nanoscale imaging of the yeast, Schizosaccharomyces pombe, by full-field transmission X-ray microscopy at 5.4 keV. AB - Three-dimensional (3D) nanoscale structures of the fission yeast, Schizosaccharomyces pombe, can be obtained by full-field transmission hard X-ray microscopy with 30 nm resolution using synchrotron radiation sources. Sample preparation is relatively simple and the samples are portable across various imaging environments, allowing for high-throughput sample screening. The yeast cells were fixed and double-stained with Reynold's lead citrate and uranyl acetate. We performed both absorption contrast and Zernike phase contrast imaging on these cells in order to test this method. The membranes, nucleus, and subcellular organelles of the cells were clearly visualized using absorption contrast mode. The X-ray images of the cells could be used to study the spatial distributions of the organelles in the cells. These results show unique structural information, demonstrating that hard X-ray microscopy is a complementary method for imaging and analyzing biological samples. PMID- 20349229 TI - Suppression of C-terminal telopeptide in hypovitaminosis D requires calcium as well as vitamin D. AB - We compared the effects of oral calcium and vitamin D separately and together on relevant variables in 22 postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L. Subjects were allocated randomly to two regimens: group 1 received 1 week of calcium 1,000 mg, followed by 7 weeks with additional vitamin D3 1,000 i.u. daily; group 2 received 7 weeks of D3 1,000 i.u. daily, followed by 1 week with additional calcium 1,000 mg. We measured serum calcium, phosphate, PTH, 25OHD, CTX, and ALP at baseline and after 1 and 8 weeks in group 1 and after 7 and 8 weeks in group 2. There were no significant changes in ALP from either vitamin D or calcium. Calcium caused significant elevation of serum 25OHD as well as major suppression of serum CTX, which could not easily be accounted for by suppression of PTH. Vitamin D caused no significant change in any variable except elevation of serum 25OHD. The suppressive effect of calcium (whether given first or second) on serum CTX was threefold greater than that of vitamin D (whether given first or second) (P < 0.001), although their suppressive effects on serum PTH were the same. Calcium and vitamin D yielded greater and more significant effects on all variables (except ALP) than either treatment alone. We suggest that calcium may elevate serum 25OHD by prolonging its half-life and that it may have an inhibitory effect on bone resorption independent of, or in addition to, its suppression of PTH. PMID- 20349230 TI - Diffusion tensor imaging of the cortical plate and subplate in very-low-birth weight infants. AB - BACKGROUND: Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. OBJECTIVE: Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. MATERIALS AND METHODS: As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. RESULTS: Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. CONCLUSION: Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values. PMID- 20349232 TI - Treatment of reverse oblique trochanteric femoral fractures with proximal femoral nail. AB - Treatment of reverse oblique trochanteric femoral fractures is still challenging. We present the results of our proximal nailing surgery performed for reverse obliquity intertrochanteric fractures using two lag screws and evaluated the quality of the reduction, operative time, complications and functional status of the patients. Fifteen patients with AO/OTA 31 A-A3 fractures were treated by proximal femoral nailing in our trauma centre. The mean Harris hip score was 74.66 (range 65-96) and the mean Barthel activity score was 15.71 (range 12-20). The mean duration of surgery was 48 minutes and the average consolidation time was 8.6 weeks. No intraoperative complications or postoperative technical failures and no stress shielding as evidenced by the lack of cortical hypertrophy at the level of the tip of the implant were detected. Intramedullary nailing with proximal femoral nails may be a good option in the treatment of reverse obliquity intertrochanteric fractures. PMID- 20349231 TI - Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study. AB - PURPOSE: Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. METHODS: We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using (18)F FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. RESULTS: The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. CONCLUSION: These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. PMID- 20349234 TI - Juvenile and adult-onset systemic lupus erythematosus: an ethnicity-based comparison. PMID- 20349235 TI - Monoarticular septic arthritis in a patient with juvenile rheumatoid arthritis under etanercept treatment. AB - A 7-year-old girl with polyarticular type juvenile rheumatoid arthritis (JRA) presented with acute onset of right hip pain with limited range of motion and fever within the past two days. She had received etanercept for more than one year. Percutaneous arthrocentesis was performed and showed a white blood cell count of 84150/MUL in the synovial fluid, although the culture showed negative results. The fever and right hip pain completely resolved after antibiotic treatment. Herein, we report the first case of septic monoarthritis of JRA under etanercept treatment. PMID- 20349236 TI - Programmed initiation of hemodialysis for systemic amyloidosis patients associated with rheumatoid arthritis. AB - Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a well-known complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients; however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixty-three patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future. PMID- 20349237 TI - Invasive aspergillosis related with azathioprine-induced leucopenia without mutant allele of thioprine methyltransferase in a patient with rheumatoid arthritis. PMID- 20349238 TI - Polymorphisms of tumor necrosis factor-alpha promoter region for susceptibility to HLA-B27-positive ankylosing spondylitis in Korean population. AB - This study designed to assess the relationship between tumor necrosis factor (TNF)-alpha promoter polymorphisms and disease susceptibility to human leukocyte antigen (HLA)-B27-positive ankylosing spondylitis (AS). One hundred and nineteen HLA-B27(+) AS patients, 95 HLA-B27(+) healthy controls, and 135 random healthy controls were enrolled in this study. Six single nucleotide polymorphisms (SNPs) of the TNF-alpha promoter at positions -1031T/C, -863C/A, -857C/T, -646G/A, 308G/A, and -238G/A were analyzed. Differences between groups were evaluated using the chi-square test or Fisher's exact test. Haplotypes from each SNP were constructed, and differences in haplotypic frequencies between groups were evaluated. There were significant differences in the allelic and genotypic frequencies of 1031T/C, -863C/A, and -857C/T TNF-alpha promoters polymorphisms between HLA-B27(+) AS patients and random controls, but not between patients with AS and HLA-B27(+) healthy individuals. TNF-alpha polymorphisms did not influence the extra-spinal clinical features in patients with AS. The haplotypic sequence 1031T/-863C/-857C/-308G increased the risk of susceptibility to AS compared to random controls (P (corr) < 0.001, OR = 2.756, 95% CI = 1.894-4.010), whereas the sequence -1031C/-863A/-857C/-308G appeared to be associated with decreased susceptibility to AS compared to random controls (P (corr) = 0.006, OR = 0.396, 95% CI = 0.231-0.679). This study indicates that TNF-alpha promoter polymorphism between controls and AS patients with HLA-B27(+) genetic background is not associated with susceptibility to AS. However, TNF-alpha polymorphism, irrespective of HLA-B27, increases risk of susceptibility to AS in general population. PMID- 20349239 TI - Association of cytosine-adenine repeat polymorphism of the estrogen receptor-beta gene with rheumatoid arthritis symptoms. AB - The influence of the polymorphism of the estrogen receptor-beta gene, cytosine adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established: or=22 repeats (long L); and 3 kinds of genotypes (SS, SL, LL) were found. In RA patients, the L allele frequency was higher (OR = 2.03; P 75% reduction in Bcl-2 expression in peripheral blood mononuclear leucocytes was seen more frequently in patients who achieved stable disease than in progressing patients. CONCLUSIONS: The maximal planned dose levels of oblimersen and gemcitabine in combination were well tolerated. Only one DLT (edema) occurred. There was a correlation between Bcl-2 reduction and stable disease. The recommended doses of the drugs for future studies are 7 mg/kg/day of oblimersen on days 1-5, and gemcitabine 1,500 mg/m(2) on day 5, every two weeks. PMID- 20349266 TI - Rapid recurrence of craniopharyngioma following recombinant human growth hormone replacement. PMID- 20349265 TI - The anti-invasive activity of synthetic alkaloid ethoxyfagaronine on L1210 leukemia cells is mediated by down-regulation of plasminogen activators and MT1 MMP expression and activity. AB - Quaternary benzo[c]phenanthridines such as fagaronine are natural substances which have been reported to exhibit anticancer and anti-leukemic properties. However, the therapeutic use of these molecules is limited due to the high dose required to exhibit anti-tumor activity and subsequent toxicity. In this study, we describe the therapeutic potential of a new derivative of fagaronine, Ethoxyfagaronine (N-methyl-12-ethoxy-2hydroxy-3, 8, 9-trimethoxybenzo[c] phenanthridiniumchlorhydrate) as an anti-leukemic agent. Cytotoxic activity and cell growth inhibition of Ethoxyfagaronine (Etxfag) was tested on murine L1210 leukemia cells using trypan blue assay and MTT assay. At the concentration of 10( 7) M, Etxfag induced less than 10% of cell death. Etxfag (10(-7) M) was tested on L1210 cell invasiveness using matrigelTM precoated transwell chambers and efficiently reduces the invasive potential of L1210 cells by more than 50% as compared with untreated cells. Western blot and immunofluorescence experiments showed that Etxfag decreased both MT1-MMP expression and activation at the cell surface, decreased plasmin activity by down-regulating u-PAR and uPA expression at the cell surface and increasing PAI-1 secretion in conditioned media. The set of our findings underscore the therapeutic potential of ethoxyfagaronine as a new potential anticancer agent able to prevent leukemic cell dissemination. PMID- 20349267 TI - Seed-expressed casein kinase I acts as a positive regulator of the SeFAD2 promoter via phosphorylation of the SebHLH transcription factor. AB - Microsomal oleic acid desaturase (FAD2) catalyzes the first committed step of the biosynthesis of polyunsaturated fatty acids via extra-plastidial desaturation of oleic acid to linoleic acid. In the regulatory mechanism controlling seed specific SeFAD2 expression, trans-activation of the seed-specific SeFAD2 promoter is mediated by the SebHLH transcription factor (Kim et al. in Plant Mol Biol 64:453-466, 2007). In this study, a protein interacting with SebHLH was isolated from yeast two-hybrid analysis. The protein shares approximately 80% sequence identity with other putative casein kinases and was named SeCKI (Sesame Casein Kinase I). SeCKI transcripts were predominantly expressed in developing sesame seeds and were induced approximately threefold by exogenous application of ABA. eGFP:SeCKI fusion protein was localized to the nucleus. The SeCKI protein specifically bound to SebHLH. The SeCKI protein was autophosphorylated in a calcium-independent manner and transphosphorylated the SebHLH protein. Both the SebHLH and the SeCKI genes or both the SebHLH and mutated SemCKI (K182G) genes, under the control of CaMV 35S promoter, and the GUS reporter gene driven by SeFAD2 promoter containing E- and G-Box motifs were co-expressed in developing sesame seeds. This co-expression revealed that SeCKI enhanced the SebHLH-mediated transactivation of the SeFAD2 gene promoter via phosphorylation of the SebHLH transcription factor. PMID- 20349268 TI - Leisure time physical activity in adulthood is positively associated with bone mineral density 22 years later. The Tromso study. AB - Although the positive association between physical activity and bone mineral density (BMD) is well established, few epidemiological studies have investigated the long-term associations between physical activity during adulthood and BMD later in life. The aim of this prospective, population-based study was to examine the association between leisure time physical activity in adulthood and areal BMD (aBMD) later in life. We examined 1,766 women and 1,451 men aged 20-54 years at baseline who were followed up 22 years later, as part of a population-based study in Norway. Leisure time physical activity was assessed by questionnaire at baseline and follow-up. aBMD was measured at the hip and forearm at follow-up, using X-ray absorptiometry. The association between aBMD and physical activity was analyzed using general linear models. We observed a positive linear trend in aBMD across physical activity levels in both women and men, after adjustments for baseline age, height, weight, and smoking status (P < 0.05). The relationship between aBMD and leisure time physical activity was consistent over different sites of the hip (total hip, femoral neck and trochanter area) and forearm (distal and ultradistal area). In a subsample of 2,436 men and women under 70 years of age, those who where sedentary at both baseline and follow-up (6%) had lower aBMD than those who were moderately active or active at both baseline and follow-up (71%) (P 0.10). Analyses of 638 patients >65 years of age and 231 of southern European ethnicity produced similar results. CONCLUSIONS/INTERPRETATION: Serum uric acid was not an independent predictor of CVD or all-cause mortality in our community-based type 2 patients. Fasting serum uric acid concentrations do not appear to be prognostically useful in type 2 diabetes. PMID- 20349346 TI - Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice. AB - AIMS/HYPOTHESIS: Metformin, the major target of which is liver, is commonly used to treat type 2 diabetes. Although metformin activates AMP-activated protein kinase (AMPK) in hepatocytes, the mechanism of activation is still not well known. To investigate AMPK activation by metformin in liver, we examined the role of reactive nitrogen species (RNS) in suppression of hepatic gluconeogenesis. METHODS: To determine RNS, we performed fluorescence examination and immunocytochemical staining in mouse hepatocytes. Since metformin is a mild mitochondrial complex I inhibitor, we compared its effects on suppression of gluconeogenesis, AMPK activation and generation of the RNS peroxynitrite (ONOO( )) with those of rotenone, a representative complex I inhibitor. To determine whether endogenous nitric oxide production is required for ONOO(-) generation and metformin action, we used mice lacking endothelial nitric oxide synthase (eNOS). RESULTS: Metformin and rotenone significantly decreased gluconeogenesis and increased phosphorylation of AMPK in wild-type mouse hepatocytes. However, unlike rotenone, metformin did not increase the AMP/ATP ratio. It did, however, increase ONOO(-) generation, whereas rotenone did not. Exposure of eNOS-deficient hepatocytes to metformin did not suppress gluconeogenesis, activate AMPK or increase ONOO(-) generation. Furthermore, metformin lowered fasting blood glucose levels in wild-type diabetic mice, but not in eNOS-deficient diabetic mice. CONCLUSIONS/INTERPRETATION: Activation of AMPK by metformin is dependent on ONOO( ). For metformin action in liver, intra-hepatocellular eNOS is required. PMID- 20349348 TI - Near-infrared quantum dots for deep tissue imaging. AB - Developments in nanotechnology have paved the way for the early detection, treatment, and prevention of several tumors which affect mankind. In the past few years, near-infrared (NIR) fluorescence imaging techniques have emerged that enable the in vivo imaging of physiological, metabolic, and molecular function. The NIR window, also known as the diagnostic window (700-900 nm), can be explored for sensitive detection techniques. Nanoparticles, particularly semiconductor quantum dots (QDs), can be utilized for the purpose of optical imaging. These semiconductor QDs possess novel electronic, optical, magnetic, and structural properties which are quite different from those of bulk materials. NIR QDs with these unique properties can be utilized as contrast agents for optical imaging, particularly for deep tissue imaging. Deep tissue imaging provides more information about the pathological status of the disease, which makes the treatment more effective and efficient. In this review we highlight the importance of NIR QDs as probes for optical imaging. We describe the different types of NIR QDs, their synthesis, and their application for deep tissue imaging along with recently developed self-illuminating NIR QDs. PMID- 20349349 TI - Identification and differentiation of dragon's blood in works of art using gas chromatography/mass spectrometry. AB - Dragon's blood is a common but non-specific name for red-coloured resins that are produced by various plants, particularly exudations from plant species belonging to the genera Dracaena and Daemonorops. Although dragon's blood is mentioned in historic sources as a colourant, it has hardly ever been identified in real artworks. This paper reports the identification and discrimination of dragon's blood produced by Dracaena cinnabari, Dracaena draco as well as Daemonorops draco and Daemonorops micracantha by means of gas chromatography/mass spectrometry (GC/MS) within the context of a routine analysis of binding media used in works of art. The detection of specific flavonoid marker compounds in both underivatised and methylated methanol extracts provided the first evidence for the use of dragon's blood from all four species in various works of art from the fifteenth to nineteenth centuries. Dragon's blood was mainly used as a red colourant in gold lacquers as well as translucent glazes and paints, e.g. in reverse-glass paintings (Hinterglasmalerei). PMID- 20349347 TI - Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis. AB - Cardiac disease in diabetes mellitus and in the metabolic syndrome consists of both vascular and myocardial abnormalities. The latter are characterised predominantly by diastolic dysfunction, which has been difficult to evaluate in spite of its prevalence. While traditional Doppler echocardiographic parameters enable only semiquantitative assessment of diastolic function and cannot reliably distinguish perturbations in loading conditions from altered diastolic functions, new technologies enable detailed quantification of global and regional diastolic function. The most readily available technique for the quantification of subclinical diastolic dysfunction is tissue Doppler imaging, which has been integrated into routine contemporary clinical practice, whereas cine magnetic resonance imaging (CMR) remains a promising complementary research tool for investigating the molecular mechanisms of the disease. Diastolic function is reported to vary linearly with age in normal persons, decreasing by 0.16 cm/s each year. Diastolic function in diabetes and the metabolic syndrome is determined by cardiovascular risk factors that alter myocardial stiffness and myocardial energy availability/bioenergetics. The latter is corroborated by the improvement in diastolic function with improvement in metabolic control of diabetes by specific medical therapy or lifestyle modification. Accordingly, diastolic dysfunction reflects the structural and metabolic milieu in the myocardium, and may allow targeted therapeutic interventions to modulate cardiac metabolism to prevent heart failure in insulin resistance and diabetes. PMID- 20349350 TI - Analysis of caffeic acid derivatives in echinacea extracts by liquid chromatography particle beam mass spectrometry (LC-PB/MS) employing electron impact and glow discharge ionization sources. AB - A liquid chromatography-particle beam/mass spectrometry (LC-PB/MS) method with electron impact (EI) and glow discharge (GD) ionization sources is presented for the determination of caffeic acid derivatives in echinacea tinctures. In this work, two commercially available echinacea ethanolic extracts were used as the test samples for the separation, identification, and quantification of the caffeic acid derivatives (caffeic acid, chlorogenic acid, cichoric acid, and caftaric acid), which are suggested to have beneficial medicinal properties. Detailed evaluations of the two primary controlling parameters for EI (electron energy and source block temperature) and GD (discharge current and pressure) sources were performed to determine optimal instrument operation conditions. The mass spectra obtained from both ion sources provide clear and simple molecular fragmentation patterns for each of the target analytes. The absolute detection limits for the caffeic acid derivatives were determined to be at subnanogram levels for both the EI and GD sources. The separation of the caffeic acid derivatives in echinacea was accomplished by reversed-phase chromatography using a C(18) column and a gradient elution system of water containing 0.1% trifluoroacetic acid and methanol, with an analysis time of less than 40 min. A standard addition method was employed for the quantification of each of the caffeic acid derivatives in the tincture. PMID- 20349351 TI - Beneficial use of immunoglobulins in the treatment of Sydenham chorea. AB - This double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional lability and muscle weakness, is one of the major criteria of acute rheumatic fever. Treatment of SC is typically limited to supportive care and palliative medications. Curative treatment is still in the experimental stage. Recent research on patients with SC proved that antibodies against the group A streptococcus cross-react with epitopes of neurons in the basal ganglia, namely, intracellular tubulin and extracellular lysoganglioside. Therefore, immune modulating therapy by means of prednisone, plasma exchange and IVIG are mentioned in the literature as possible effective treatment. Beneficial effect of IVIG has been shown in several diseases with molecular mimicry as the underlying pathophysiology. In this paper, we describe two girls aged 11 and 13 years, respectively, who presented with SC having severe disabilities in their daily live. We treated both patients with IVIG 400 mg/kg/day for 5 days. Treatment was tolerated well and had a pronounced positive effect. Shortly after the drug was administered, all signs and symptoms disappeared in both patients. Based upon these patients, we highlight IVIG as a serious treatment option for SC. PMID- 20349352 TI - Crenotherapy: a neglected resource for human health now re-emerging on sound scientific concepts. AB - Recent mechanistic evidence demonstrates that spa-based therapy (or, as we propose, crenotherapy from the Greek word kapparhoepsilonnueta, spring fountain) is indeed based on solid scientific data. This mini-review highlights the latest insights into the mechanisms of crenotherapy derived from in vitro experiments, studies on animal models, and carefully designed clinical trials. Although more basic and clinical data are still needed, crenotherapy is coming of age as a modern, scientifically sound therapy. As the underlying mechanisms are uncovered, it is becoming possible to choose the most appropriate applications of this centuries-old practice, possibly reducing medical costs, thus explaining the current worldwide renewed interest in crenotherapy. PMID- 20349353 TI - Determinants of quality of life in patients with advanced cancer. AB - PURPOSE: Improving health-related quality of life (HRQL) is the main goal of palliative care and an important outcome for oncology trials. This study examines medical and sociodemographic determinants of HRQL in outpatients with advanced cancer. METHODS: Patients with metastatic gastrointestinal, genitourinary, breast, lung or gynecological cancer, ECOG 0-2, and clinical prognosis of 6 months to 2 years were recruited from outpatient medical oncology clinics. HRQL was measured using the FACT-G questionnaire and the FACIT-Sp meaning and peace (existential) subscale. The influence of demographic and medical characteristics on HRQL was determined using t tests and analysis of variance, with Tukey's correction for multiple comparisons. Multivariate linear regression was used to determine independent predictors. RESULTS: Of 285 patients, 57% were female and the median age was 61 years; 44% were alive at latest follow-up; and of those deceased, the mean survival time was 10 months. The strongest determinants of overall HRQL were increased age (p < 0.001), good performance status (PS; p < 0.001) and survival time >6 months (p = 0.001). Compared to patients receiving cancer treatment, those awaiting new treatment had worse emotional well-being (p < 0.001), while those on surveillance or whose treatment had been stopped had worse existential well-being (p = 0.03). Male gender predicted better emotional and physical well-being and lower income predicted worse social well-being. CONCLUSIONS: Age, PS, survival time, and treatment status are important determinants of HRQL in patients with advanced cancer. Decision aids, open communication, and involvement of supportive care specialists may improve emotional and existential distress associated with changing or stopping cancer treatment. PMID- 20349355 TI - A computational study of the mechanism of the unimolecular elimination of alpha,beta-unsaturated aldehydes in the gas phase. AB - The mechanism for the decarbonylation of (E)-2-butenal and (E)-2-methyl-3-phenyl 2-propenal was studied with different levels of ab initio and DFT methods. Reactants, products and transition structures were optimized for two kinds of reaction channel: a one-step reaction which involves a three-membered cyclic transition state, and a two-step reaction which involves an initial four-membered cyclic transition state. According to our calculations, these two possible mechanisms entail similar energetic costs, and there are only small differences depending on the reactant. The elimination of (E)-2-methyl-3-phenyl-2-propenal yields different products depending on the channel followed. Only one of the three possible one-step mechanisms leads directly to (E)-beta-methylstyrene (the main product according to experiment). This fact is reasonably well reproduced by our results, since the corresponding transition state gave rise to the lowest activation Gibbs free energy. PMID- 20349354 TI - Effect of office-based brief high-impact exercise on bone mineral density in healthy premenopausal women: the Sendai Bone Health Concept Study. AB - Although there is ample evidence supporting the effectiveness of physical activity in the prevention and treatment of osteoporosis, there are no previous studies to examine the effect of office-based brief high-impact exercise (HIE) on bone mineral density (BMD) in healthy premenopausal women. This study evaluated the effects of office-based HIE on BMD in healthy premenopausal Japanese women. Ninety-one healthy premenopausal women were randomized to receive stretching exercise (SE) or HIE (stretching, along with up to 5 * 10 vertical and versatile jumps) for 12 months. The BMD of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. Several cardiovascular risk factors and leg strength also were assessed. An accelerometer-based recorder was used to measure daily impact loading in four 1-week samples. The progression of the HIE program was ensured by the accelerometer. Thirty-three women (71.7%) in the SE group and 34 (75.6%) in the HIE group completed the study. There was a significant difference in the change in the femoral neck BMD between the groups in favor of the HIE group [0.6% (95% CI: -0.4, 1.7) vs. -1.0% (95% CI: -2.2, 0.2)]. Adiponectin, LDL, HDL, and the leg strength of participants in both the groups improved during the intervention. These finding suggested that office based brief HIE can be recommended for premenopausal women for preventing bone mineral loss. PMID- 20349356 TI - Surgical management of severe rigid tuberculous kyphosis of dorsolumbar spine. AB - To assess the effectiveness of deformity correction and safety of the two major corrective spinal surgical procedures, 35 patients, aged 14-47 years, were placed into two groups according to procedures performed. Sixteen patients (group A) had four-stage procedures including initial halo-pelvic distraction after anterior release and a subsequent three procedural steps plus brace. Nineteen patients (group B) had one-set two-stage procedures: wire segmental stabilisation in eight cases and rod/hook and/or pedicle screw stabilisation in 11 cases. Average preoperative kyphosis in group A was 88 degrees and postoperative at zero, three, six, and 18 months were 29, 33, 35 and 35, respectively, while those of group B were 86 preoperative and postoperative 27, 31, 33, and 33, respectively. Neural complication developed in five cases: one in group A and four in group B. It was concluded that the one-set two-stage procedure is more efficient, time saving, and cost-effective, though it is highly challenging with relatively high rates of neural complication. PMID- 20349357 TI - Arthroplasty of the lunate using bone marrow mesenchymal stromal cells. AB - Mesenchymal stromal cells have the potential to differentiate into a variety of mesenchymal tissues such as bone, cartilage and ligaments. The potential for the regeneration of bone with cartilage coverage has still not been achieved. We evaluated the ability of bone marrow mesenchymal stromal cells to regenerate osteochondral defects in the cavity of the lunate in an animal model. Autologous mesenchymal stromal cells were harvested from the iliac crest of New Zealand white rabbits and expanded in vitro. Total lunate excision was performed in 24 animals and the isolated cells were loaded onto scaffolds. Cell-free scaffolds were implanted in the lunate space of the right wrists of all animals, and the left lunate spaces were filled with predifferentiated, cell-loaded scaffolds. Radiographic and histological analyses were performed after two, six and 12 weeks. In addition, the animals were injected with a fluorescent agent every five days, starting at day 30. After two and six weeks there was no radiographic evidence of ossification, whereas after 12 weeks all animals showed radiographic evidence of ossification. Histological sections showed increasing evidence of cartilage-like cell formation at the edges and new bone tissue in the centre of the newly formed tissue in all groups. The histological examinations showed that bone tissue was located around the newly incorporated vascularisation. This study demonstrated that newly formed vascularisation is necessary for the regeneration of bone tissue with cell-loaded scaffolds. PMID- 20349358 TI - Total hip replacement in congenital high hip dislocation following iliofemoral monotube distraction. AB - The aim of this study was to prospectively evaluate our single-centre one- and five-year results of anatomically correct cementless total hip arthroplasty in unilateral and bilateral Crowe type IV high hip dislocations in ten hips following iliofemoral monotube soft tissue distraction. Six consecutive patients (five females and one male) with unilateral and two female patients with bilateral high hip dislocation with an average age of 46 years and height of dislocation up to 110 mm were treated in our institution. Limb lengthening was achieved up to 100 mm. The mean leg-length-discrepancy was -4 mm postoperatively. Harris hip score increased significantly at one year (p < 0.001) and significantly further (p < 0.05) at five years postoperative. WOMAC, VAS pain scale as well as gait and pain-free walking distance also improved significantly at follow-up. Two pin infections and one temporary peroneal nerve palsy occurred during monotube extension. Three cup protrusions that required revision surgery were observed in two patients. This study shows that iliofemoral distraction prior to total hip replacement achieves leg length equality and improved gluteal function and therefore gait in patients with Crowe type IV hip dislocation. PMID- 20349359 TI - Decompressive craniectomy for neurotrauma: the limitations of applying an outcome prediction model. AB - BACKGROUND: There is currently much interest in the use of decompressive craniectomy for patients with severe head injury. A number of studies have demonstrated that not only can the technique lower intracranial pressure but can also improve outcome. Whilst many patients who would otherwise have died or had a poor outcome now go on to make a good recovery, there is little doubt that complications can have a very significant impact on long term outcome. METHODS: By using the corticosteroid randomisation after significant head injury (CRASH) collaborators outcome prediction model, three patients were selected who had a similar outcome prediction. All three patients developed intracranial hypertension following trauma and had a decompressive craniectomy. RESULTS: Despite having a similar outcome prediction only one patient made an uneventful recovery. The remaining two patients suffered significant complications. CONCLUSIONS: This report illustrates the potential clinical applications and limitations of an outcome prediction model and demonstrates the impact that complications can have on eventual outcome. PMID- 20349360 TI - Evaluation of the protective effect of bovine lactoferrin against lipopolysaccharides in a bovine mammary epithelial cell line. AB - Lactoferrin (Lf) is a non-haem iron-binding glycoprotein with a molecular weight of about 80 kDa, synthesized by glandular epithelial cells and stored in the secondary granules of neutrophils. The physiological significance of Lf is related to non-specific immune defence against pathogens, immunomodulatory activity, iron homeostasis, antioxidant properties and regulation of cell growth. Lf is a bioactive component of the mammary secretions and its modulatory and defensive functions do affect the newborn and the mammary gland as well. In this work a bovine mammary epithelial cell line (BME-UV1) was used as an in vitro model of the bovine mammary epithelium to examine the protective role of exogenous bovine Lf (bLf) against the cytotoxic damage induced by bacterial lipopolysaccharides (LPS) and the endogenous bLf mRNA expression after LPS exposure. In the in vitro model used, exogenous bLf exerts a protective effect against endotoxin cytotoxicity, which could be mediated by the LPS-neutralizing capability of bLf. In addition, in BME-UV1 cells the response to LPS exposure does not involve bLf mRNA expression, suggesting that this cell line lack of functional LPS-responsive elements. PMID- 20349361 TI - Retrospective research: What are the ethical and legal requirements? AB - Retrospective research is conducted on already available data and/or biologic material. Whether such research requires that patients specifically consent to the use of "their" data continues to stir controversy. From a legal and ethical point of view, it depends on several factors. The main criteria to be considered are whether the data or the sample is anonymous, whether the researcher is the one who collected it and whether the patient was told of the possible research use. In Switzerland, several laws delineate the procedure to be followed. The definition of "anonymous" is open to some interpretation. In addition, it is debatable whether consent waivers that are legally admissible for data extend to research involving human biological samples. In a few years, a new Swiss federal law on human research could clarify the regulatory landscape. Meanwhile, hospital internal guidelines may impose stricter conditions than required by federal or cantonal law. Conversely, Swiss and European ethical texts may suggest greater flexibility and call for a looser interpretation of existing laws. The present article provides an overview of the issues for physicians, scientists, ethics committee members and policy makers involved in retrospective research in Switzerland. It aims at provoking more open discussions of the regulatory problems and possible future legal and ethical solutions. PMID- 20349362 TI - Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect. AB - QUESTIONS UNDER STUDY / PRINCIPLES: Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. METHODS: We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. RESULTS: The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. CONCLUSIONS: These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland. PMID- 20349363 TI - Vaccine hypersensitivity--update and overview. AB - Concerns about possible reactions to vaccines or vaccinations are frequently raised. However, the rate of reported vaccine-induced adverse events is low and ranges between 4.8-83.0 per 100,000 doses of the most frequently used vaccines. The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500,000 to 1 per 1,000,000 doses for most vaccines. When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life-threatening reactions to vaccines are still a rare event (approximately 1 per 1,500,000 doses). The variety of reported vaccine related adverse events is broad. Most frequently, reactions to vaccines are limited to the injection site and result from a non specific activation of the inflammatory system by, for example, aluminium salts or the active microbial components. If allergy is suspected, an accurate examination followed by algorithms is the key for correct diagnosis, treatment and the decision regarding revaccination in patients with immediate-type reactions to vaccines. PMID- 20349364 TI - Stabilization of the prevalence of childhood obesity in Switzerland. AB - BACKGROUND: The prevalence of childhood obesity is increasing rapidly in most industrialised countries, but several countries, including Switzerland, have recently reported a levelling off or even a reversal of this alarming trend. STUDY AIM: Our aim was to evaluate the prevalence of childhood obesity in a national sample of Swiss school children recruited to assess iodine nutrition and with this to reconfirm a recently shown stabilising trend. DESIGN: Using a probability-proportionate-to-size cluster sampling, 6 to 12 year old children (n = 907) were recruited in a study of iodine status in Switzerland. Height and weight were measured and body mass index calculated in all children. RESULTS: The prevalence of overweight detected was 12.5% (SE = 1.6) in boys and 12.8% (1.6) in girls while 6.2% (1.1) of boys and 4.2% (0.9) of girls were classified as obese. The highest prevalence of overweight and obesity were found in the Southern region and in bigger cities (>100000 inhabitants). Compared to the most recent national study in 2007, the prevalence was slightly higher, but the differences were not significant, suggesting negative sampling bias does not strongly affect surveys of paediatric adiposity in Switzerland. CONCLUSION: This present study clearly confirms the stabilisation of the prevalence of childhood overweight and obesity in Switzerland. PMID- 20349365 TI - Improving intelligence: a literature review. AB - Intelligence is associated with performance on a wide range of cognitive tasks and is a reliable predictor for educational and professional success. Therefore, the development of effective training regimens that aim to improve intelligence is of high interest. In recent years, there has been accumulating evidence that certain interventions have a positive impact on intelligence. The aim of the present paper is to provide a literature review on such studies. Despite promising results, we conclude that there are still many unknown variables and that the mechanisms that underlie improvements in intelligence are not well understood. More work is needed in order to disentangle these involved processes and to further refine existing training regimens. PMID- 20349366 TI - CT and MR imaging of chronic subdural hematomas: a comparative study. AB - QUESATIONS UNDER STUDY / PRINCIPLES: This study was designed to compare CT and MR appearances of chronic subdural haematomas as well as CT- and MR-guided measurements of haematoma thicknesses. METHODS: CT and MR images of 48 chronic subdural haematomas of 34 patients were reviewed retrospectively. The thickness measurements and imaging characteristics of haematomas were compared. RESULTS: Levelling was observed in 25% of haematomas, and most of them (60%) had intrahaematomal membranes. All membranes could be delineated by MR imaging, whereas only 27% were defined by CT. Mixed density (52%) and T1 hyperintensity (59%) were commonly observed in membraned haematomas, but the difference was not statistically significant. Haematomas were measured significantly thicker on MR images. All patients had been treated with burr-hole cranio-tomy and irrigation. CONCLUSIONS: MR imaging is more sensitive than CT in determining the size and internal structures of chronic subdural haematomas. PMID- 20349367 TI - Recent developments in occupational asthma. AB - Occupational exposures now account for 20% of adult onset asthma. Overall incidence has not declined, but recognition of the problem and substitutions have resulted in dramatic reductions in some causes of occupational asthma, particularly latex and glutaraldehyde in healthcare workers. Newer at risk workers include cleaners and those exposed to metal-working fluid. Standards of care have now been published, supported by evidence- based reviews of the literature, which are likely to require referral to centres specialising in occupational asthma for compliance. The spectrum of occupational asthma is expanding, with low-dose irritant mechanisms likely to account for some occupational asthma with latency. Eosinophilic and non-eosinophilic phenotypes are also seen, the non-eosinophilic variant having more normal non-specific responsiveness than the eosinophilic subgroup. Physiological confirmation of occupational asthma is required but remains challenging. Specific challenges may be negative in workers confirmed as having occupational asthma from workplace challenges. Serial measurements of peak expiratory flow or FEV1 are feasible in the occupational health and general respiratory clinic settings and provide a method of validation of occupational asthma in those without ready access to specific challenge testing, while minimum data quantity standards are now established which need to be achieved for optimal sensitivity/specificity. New developments in the analysis of serial mea-surements of peak expiratory flow comparing the mean hourly values on work and rest days have shown good specificity and sensitivity from shorter records (but more frequent readings) than needed for the standard Oasys score. PMID- 20349368 TI - How name descriptiveness impacts proper name learning in young and older adults. AB - To elucidate the impact of name descriptiveness and aging on learning new names, 26 young and 26 healthy older participants learned visibly-descriptive (e.g., Lengthy for a giraffe), psychologically-descriptive (e.g., Classy), and non descriptive (e.g., Sam) proper names for previously-unknown cartoon characters. More visibly-descriptive names were learned than psychologically- or non descriptive names, which did not differ from each other. There was also a differential benefit for older adults when the name was visibly-descriptive of the referent, such that older adults learned visibly-descriptive names as well as young adults but there were substantial age-related deficits in learning psychologically- and non-descriptive names. PMID- 20349369 TI - Evaluation of inner-outer space distinction and verbal hallucinations in schizophrenia. AB - INTRODUCTION: Verbal hallucinations could result from attributing one's own inner speech to another. Inner speech is usually experienced in inner space, whereas hallucinations are often experienced in outer space. To clarify this paradox, we investigated schizophrenia patients' ability to distinguish between speech experienced in inner space, and speech experienced in outer space. METHODS: 32 schizophrenia patients and 26 matched healthy controls underwent a two-stage experiment. First, they read sentences aloud or silently. Afterwards, they were required to distinguish between the sentences read aloud (experienced in outer space), the sentences read silently (experienced in inner space), and new sentences not previously read (no space coding). The sentences were in the first, second, or third person in equal proportions. Linear mixed models were used to investigate the effects of group, sentence location, pronoun, and hallucinations status. RESULTS: Schizophrenia patients were similar to controls in recognition capacity of sentences without space coding. They exhibited both inner-outer and outer-inner space confusion (they confused silently read sentences for sentences read aloud, and vice versa). Patients who experienced hallucinations inside their head were more likely to have outer-inner space bias. CONCLUSIONS: For speech generated by one's own brain, schizophrenia patients have bidirectional failure of inner-outer space distinction (inner-outer and outer-inner space biases); this might explain why hallucinations (abnormal inner speech) could be experienced in outer space. Furthermore, the direction of inner-outer space indistinction could determine the spatial location of the experienced hallucinations (inside or outside the head). PMID- 20349370 TI - Estimated intake of benzoic and sorbic acids in Denmark. AB - The monitoring of food additives and recent dietary surveys carried out in Denmark have earlier been used to estimate the intake of sweeteners and nitrite in relation to acceptable daily intakes. The ubiquitous use of the preservatives benzoic and sorbic acids raises the question of the magnitude of the intake of these preservatives in relation to acceptable daily intakes. This area is explored in this paper. The content of benzoic and sorbic acids in all food groups, where they are allowed, was monitored in Denmark 17 times between 2001 and 2006 with a total of 1526 samples. Transgressions of maximum limits, illegal use or declaration faults were found in about 3% of samples. From repeated investigations on fat-based foods (salads and dressings), marmalade and stewed fruit, it is concluded that the amounts used in industry have been relatively stable throughout the whole period, although limited data for marmalade show some variation. Most foods in the categories soft drinks, dressings, fat-based salads, pickled herrings, and marmalade contain benzoic and sorbic acid, and sliced bread also contains in some cases sorbic acid. The median daily intake and intake distribution of benzoic and sorbic acids were calculated with data from the Danish National Survey of Dietary Habits and Physical Activity (age from 4 to 75 years) conducted in 2000-2004 with 5785 participants. The median intakes of both benzoic acid and sorbic acid are well below the acceptable daily intakes of 0-5 and 0-25 mg kg(-1) body weight (bw) day(-1) for benzoic and sorbic acid, respectively. However, the 90th percentile based on the average of the samples with a content of benzoic acid is higher than the acceptable daily intake for both men and women, with the highest value of 16 mg kg(-1) bw day(-1) for both boys and girls in the 4-6-year-old age group. Based on the average of all samples, the 95th percentile is over the acceptable daily intake for men up to 34 years and for women up to 24 years, and the 90th percentile for men up to 18 years and for women up to 10 years. Soft drinks, salads and dressings are the main contributors to benzoic acid intake. The sorbic acid intake based on the average of all samples is well below the acceptable daily intake. However, for the intake based on the average of samples with content, the 95th percentile exceeds the acceptable daily intake. This is caused by the dominating contribution to the intake of sorbic acid from sliced bread, but since only seven out of 42 samples have added sorbic acid, the calculation based on the average of samples with content will exaggerate the intake. With a built-in safety factor of 100 in the acceptable daily intakes and judging from the literature, the high intakes of benzoic acid should not cause any concern for ill-effects. However, there must be a reason to reconsider the maximum limits especially for benzoic acid in soft drinks, dressings and salads and for sorbic acid in sliced bread. PMID- 20349371 TI - Contamination by moulds of grape berries in Slovakia. AB - This paper describes the first map, albeit partial, of toxigenic fungi re isolated from grape berries collected in three out of the six most important Slovakia winemaking areas in two different periods of the harvest year 2008. Low temperatures and high relative humidity during July 2008 favoured the development of grape fungal diseases that cause rots such as Plasmopara, Uncinula, Botrytis, Metasphaeria, Elsinoe, and Saccharomycetes. In the analysed samples, the following genera of toxigenic fungi were identified in the range of 1-4%: Aspergillus, Alternaria, Cladosporium, Epicoccum, Fusarium, Penicillium, Rhizopus, Ulocladium, and Trichoderma Trichothecium, while the genera Aspergillus, Alternaria, Fusarium, and Penicillium were in the range 11-29%. A. niger, A. carbonarius, some strains of A. carbonarius-with 'crystals' and strains of A. uvarum-uniseriate were identified; these species are considered ochratoxigenic (able to produce variable amounts of toxins). In addition, a non ochratoxigenic strain of A. ibericus and a Fusarium strain able to biosynthesize small amount of fumonisins, beauvericin, and enniatins were identified. P. expansum, able to produce citrinin, represents 29.7%, of the Penicillium genus together with P. verrucosum, P. glabrum, P. citrinum, and P. crustosum. An analysis for the identification and quantification of the main toxins: ochratoxin A, fumonisins, beauvericin, enniatins, and fusaproliferin was performed on grape samples; it was consistent with the results of the mycological analysis. Toxigenic fungi should be checked throughout the years and their occurrence compared with all environmental factors to avoid health risks. PMID- 20349372 TI - Reduction of Fusarium head blight and deoxynivalenol in wheat with early fungicide applications of prothioconazole. AB - Numerous studies have identified the benefit of fungicides applied at flowering (Zadoks Growth Stage (GS) 59-69) in the reduction of Fusarium head blight and the reduction of deoxynivalenol (DON) in harvested wheat grain. Two experiments were performed to identify the ability of prothioconazole (Proline) at three timings to reduce Fusarium head blight and resulting DON in harvested grain of wheat. Prothioconazole (150 g ha(-1)) was applied to plots of wheat at GS31, GS39, and GS65 in a full-factorial design. Plots were inoculated with Fusarium-infected oat grain at GS30 and mist-irrigated at GS65 to encourage head blight development. Plots were assessed for head blight symptoms at GS77 and harvested grain was analysed for yield, specific weight, thousand grain weight, and DON. Factorial analysis of variance (ANOVA) identified prothioconazole applications at each timing that resulted in significant reductions in Fusarium head blight and DON. The control achieved with combinations of spray timings was additive with no significant interactions. The control of Fusarium head blight at GS31, GS39, and GS65 was 50, 58 and 83%, respectively. The reduction in Fusarium head blight achieved by all three timings combined was 97% compared to the fully untreated control plots. The reduction of DON after application of prothioconazole at GS31, GS39, and GS65 was 27%, 49%, and 57%, respectively. The application of prothioconazole at all three timings achieved 83% reduction of DON compared with the fully untreated control plots. These experiments have determined, for the first time, significant additional head blight disease control and mycotoxin reduction with applications of a fungicide before flowering. PMID- 20349373 TI - Occurrence of polycyclic aromatic hydrocarbons throughout the processing stages of erva-mate (Ilex paraguariensis). AB - The presence of polycyclic aromatic hydrocarbons (PAHs) in mate (Ilex paraguariensis) is believed to be due to the degradation of mate compounds and the burning of wood during the "sapeco" (rapid drying process) and the final drying steps, which are the most important processing stages in mate production. Due to the high toxicity of these compounds, studies on their presence in mate are extremely important. The aim of this study was to evaluate PAH levels in mate throughout the processing stages of its production. The PAHs were measured in samples collected at different stages of mate processing. Total PAHs content ranged widely (443-9001 microg/kg) in the samples, with the highest PAHs levels recorded during the mate drying step. The results indicate that the processing method currently used in mate production may lead to an increase in PAHs levels in the final product. PMID- 20349374 TI - Descriptive modelling to predict deoxynivalenol in winter wheat in the Netherlands. AB - Predictions of deoxynivalenol (DON) content in wheat at harvest can be useful for decision-making by stakeholders of the wheat feed and food supply chain. The objective of the current research was to develop quantitative predictive models for DON in mature winter wheat in the Netherlands for two specific groups of end users. One model was developed for use by farmers in underpinning Fusarium spp. disease management, specifically the application of fungicides around wheat flowering (model A). The second model was developed for industry and food safety authorities, and considered the entire wheat cultivation period (model B). Model development was based on observational data collected from 425 fields throughout the Netherlands between 2001 and 2008. For each field, agronomical information, climatic data and DON levels in mature wheat were collected. Using multiple regression analyses, the set of biological relevant variables that provided the highest statistical performance was selected. The two final models include the following variables: region, wheat resistance level, spraying, flowering date, several climatic variables in the different stages of wheat growing, and length of the period between flowering and harvesting (model B only). The percentages of variance accounted for were 64.4% and 65.6% for models A and B, respectively. Model validation showed high correlation between the predicted and observed DON levels. The two models may be applied by various groups of end-users to reduce DON contamination in wheat-derived feed and food products and, ultimately, reduce animal and consumer health risks. PMID- 20349375 TI - Strategies to reduce mycotoxin levels in maize during storage: a review. AB - Maize (Zea mays L.) is one of the main cereals as a source of food, forage and processed products for industry. World production is around 790 million tonnes of maize because as a staple food it provides more than one-third of the calories and proteins in some countries. Stored maize is a man-made ecosystem in which quality and nutritive changes occur because of interactions between physical, chemical and biological factors. Fungal spoilage and mycotoxin contamination are of major concern. Aspergillus and Fusarium species can infect maize pre-harvest, and mycotoxin contamination can increase if storage conditions are poorly managed. Prevention strategies to reduce the impact of mycotoxin in maize food and feed chains are based on using a hazard analysis critical control point systems (HACCP) approach. To reduce or prevent production of mycotoxins, drying should take place soon after harvest and as rapidly as feasible. The critical water content for safe storage corresponds to a water activity (a(w)) of about 0.7. Problems in maintaining an adequately low a(w) often occur in the tropics where high ambient humidity make the control of commodity moisture difficult. Damage grain is more prone to fungal invasion and, therefore, mycotoxin contamination. It is important to avoid damage before and during drying, and during storage. Drying maize on the cob before shelling is a very good practice. In storage, many insect species attack grain and the moisture that can accumulate from their activities provides ideal conditions for fungal activity. To avoid moisture and fungal contamination, it is essential that the numbers of insects in stored maize should be kept to a minimum. It is possible to control fungal growth in stored commodities by controlled atmospheres, preservatives or natural inhibitors. Studies using antioxidants, essential oils under different conditions of a(w), and temperature and controlled atmospheres have been evaluated as possible strategies for the reduction of fungal growth and mycotoxin (aflatoxins and fumonisins) in stored maize, but the cost of these treatments is likely to remain prohibitive for large-scale use. PMID- 20349377 TI - An empirical case study examining effectiveness of environmental enrichment in two captive Australian Sea Lions (Neophoca cinerea). AB - This case study examined the effect of environmental enrichment on the activity budgets of a male and female Australian Sea Lion (Neophoca cinerea) housed together at Adelaide Zoo. Using non-food-related (intrinsic) and food-related (extrinsic) enrichment objects, the study conducted an ABABA (withdrawal) experimental design over a 30-day period (180 hr). The study expected extrinsically reinforcing objects to be more effective than intrinsically reinforcing objects in reducing pattern swimming. The male sea lion spent more than 45% of scans engaged in pattern swimming during the initial baseline, which was reduced by at least 25% when enrichment items were present. However, there was no evidence of stereotypic behavior in the female sea lion, indicating that individual differences may exist. When enrichment was present, the study observed more active behaviors in both nonhuman animals. They spent more time interacting with the non-food-related objects overall. Therefore, introducing simple enrichment devices offers a cheap, practical, and effective method of adding complexity to the environment, which is likely to benefit the animals' welfare and enhance the zoo-visitor experience. PMID- 20349378 TI - Noncompliance with Public Health Service (PHS) policy on humane care and use of laboratory animals: an exploratory analysis. AB - The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS's animal care and use standards must report these incidents to the NIH's OLAW. This study is an exploratory analysis of all the significant deviations reported by animal research facilities to OLAW during a 3-month period. The study identifies the most common issues reported and species involved. The study found that the majority of the incidents resulted in animal pain and distress and that 75% ended in animal death. This study offers preliminary recommendations to address the most common problems identified in this analysis. This study urges OLAW and other stakeholders to analyze larger, more recent samples of reported deviations to compare with these results and ultimately improve adherence to animal welfare standards. PMID- 20349379 TI - Aggressive behavior in two different group-housing systems for pregnant sows. AB - The study housed 120 pregnant sows from Day 29 of pregnancy to 1 week before parturition either in groups of 10 with trickle feeding (TRICKLE) or in groups of 20 with an unprotected electronic sow feeding (FITMIX). The study recorded aggressive interaction on 11 nonconsecutive days. Frequency of aggressive interactions was higher in FITMIX (p < .05); yet, intense physical contact was unusual in both systems (3% of the total interactions). Conflicts in FITMIX centered largely on the feeder (83% vs. 23% for FITMIX and TRICKLE, respectively [p < .05]); in TRICKLE, they occurred mainly in the resting area (13% vs. 48% for FITMIX and TRICKLE, respectively [p < .05]). Forty-six percent of the FITMIX sows (mostly gilts and subordinates) needed assistance to adapt to the feeding system. Eventually, 8.3% of the FITMIX sows failed to adapt and had to be removed. In conclusion, although aggressive interactions were mainly of low intensity, sequential feeding appeared to make FITMIX a more competitive feeding system. PMID- 20349380 TI - Siamangs (Hylobates syndactylus) and white-cheeked gibbons (Hylobates leucogenys) show few behavioral differences related to zoo attendance. AB - The effect of visitors on behavior and welfare of nonhuman animals in the zoo has been an active research topic during the last few decades. Although research has variously shown negative or positive impacts of zoo visitors on animals in captivity, previous primate research at Disney's Animal Kingdom suggests the importance of visual barriers in allowing animals to cope with large crowds. Examining this further, this study monitored the behavior of white-cheeked gibbons (Hylobates leucogenys) and siamangs (Hylobates syndactylus) in large, open exhibits. Behavioral data showed rates of social behavior and percentage of time engaged in solitary behavior did not differ between low and high visitor attendance days. Both gibbons and siamangs spent more time in areas away from the public on high attendance days. Supporting previous findings, results imply visual barriers and ability to retreat from crowds may have provided these animals with choice and minimized potential negative visitor impact. Future research should focus on the relationship between attendance and actual crowds at exhibits; it should utilize multi-institutional methodologies to control for variance and look for individual and demographic differences between individuals. PMID- 20349381 TI - An evaluation of exercise pen use by circus tigers (Pathera tigris tigris). AB - This study quantified the behavior of 11 tigers during periodic access to an exercise pen throughout the day and night. The study determined the amount of time spent in the pen and the percentage of time spent performing stereotypic pacing, normal locomotor behavior, and lying down while in the pen. Average access to the exercise pen was 10 hr 49 min overnight and 5 hr 30 min during the day. At night, the tigers spent 29.1% of their time in the exercise pen, during which they paced 19.6% and performed normal locomotor behavior for 23.1% of that time. By day, they spent 40.4% of their time in the exercise pen, during which they paced 10.0% and performed normal locomotor behavior 35.7% of that time. The tigers spent the rest of the time in the pen lying down. Overall, tigers will utilize an exercise pen, spending a greater percentage of time in the pen during the day than at night and also performing less stereotyped pacing than at night. PMID- 20349382 TI - Factors relevant to adoption of cats in an animal shelter. AB - This study performed a multifactor analysis of the effects of the provision of toys, cage location, and cat characteristics (activity level, age, sex, and coat color) on 111 cats available for adoption in a nonhuman animal shelter. The analysis revealed a greater adopter viewing of cats housed at eye level and of those with toys-even though the toys did not affect the cats' behavior. Adopters viewed cats who were active for longer periods of time. The active cats were more likely to be adopted during the 16-week study than cats who were less active. PMID- 20349383 TI - The legal status of cats in New Zealand: a perspective on the welfare of companion, stray, and feral domestic cats (Felis catus). AB - Pinpointing and safeguarding the welfare status of domestic cats is problematic, especially in New Zealand where cats are introduced predators with significant impact on indigenous fauna. Usually the identification of welfare status depends on conservational, legal, and public attitudes that are often contrasting. Cats may rapidly transgress definitions placed on them, confounding attempts to categorize them. In 1 generation, cats can move from a human-dependent state ("stray" or "companion") to wild ("feral"). Often this categorization uses arbitrary behavioral and or situational parameters; consequent treatment and welfare protection for these cats are similarly affected. Terminology used to describe cats is not equitable across research. However, the New Zealand Animal Welfare (Companion Cats) Code of Welfare 2007 seeks to create a new definition of the terms companion, stray, and feral. It distinguishes between cats who live within and without human social constructs. This legislation mandates that cats in human environments or indirectly dependent on humans cannot be classified as feral. Such definitions may prove vital when safeguarding the welfare of free living domestic cats and cat colonies. PMID- 20349385 TI - Age-related IQ decline is reduced markedly after adjustment for the Flynn effect. AB - Twenty-year-olds outperform 70-year-olds by as much as 2.3 standard deviations (35 IQ points) on subtests of the Wechsler Adult Intelligence Scale (WAIS). We show that most of the difference can be attributed to an intergenerational rise in IQ known as the Flynn effect. Normative data from different versions of the WAIS enabled us to estimate the degree to which the Flynn effect, rather than age related decline, contributes to differences between 20- and 70-year-olds. The Flynn effect accounted for 38-67% of the apparent age-related decline on 6 of the 11 subtests. On the other 5 subtests, all of which are categorized as verbal, the Flynn effect was larger than the age-group difference. For these verbal subtests, the Flynn effect masked a modest increase in ability as individuals grow older. Overall, the Flynn effect accounted for at least 85% of the disparity between 20- and 70-year-olds. PMID- 20349386 TI - Emotion recognition in children with profound and severe deafness: do they have a deficit in perceptual processing? AB - Findings from several studies have suggested that deaf children have difficulties with emotion identification and that these may impact upon social skills. The authors of these studies have typically attributed such problems to delayed language acquisition and/or opportunity to converse about personal experiences with other people (Peterson & Siegal, 1995, 1998). The current study aimed to investigate emotion identification in children with varying levels of deafness by specifically testing their ability to recognize perceptual aspects of emotions depicted in upright or inverted human and cartoon faces. The findings from the study showed that, in comparison with both chronological- and mental-age-matched controls, the deaf children were significantly worse at identifying emotions. However, like controls, their performance decreased when emotions were presented on the inverted faces, thus indexing a typical configural processing style. No differences were found across individuals with different levels of deafness or in those with and without signing family members. The results are supportive of poor emotional identification in hearing-impaired children and are discussed in relation to delays in language acquisition and intergroup differences in perceptual processing. PMID- 20349388 TI - Exposures and physiological responses in power tool operations: fastening vs. unfastening threaded hardware. AB - Powered hand tools have the potential to produce reaction forces that may be associated with upper extremity musculoskeletal disorders. This study examined and compared the kinetic and physiological impacts on operator upper extremities between the fastening and unfastening operations. Thirty-two healthy, right handed male operators used four tools on two joint simulators at different working heights and distances in the laboratory. Three work configurations were simulated: pistol grip tools on a vertical and horizontal surface, and right angle tools on a horizontal surface. Grip force was measured on an instrumented handle attached to each tool. Muscle activity was monitored at the wrist flexor and extensor and the upper trapezius of the right arm. Paired comparisons showed that when pistol grip tools were used, the peak torque to unfasten a joint (3.7 Nm) was significantly less than to fasten the same joint (5.7 Nm). However, the exposure time was longer for unfastening cycles (98 ms more on the horizontal surface, and 107 ms more on the vertical surface). The average grip force scaled to corresponding peak tool torque revealed that the effort to react against torque was greater in unfastening cycles than in fastening cycles for all work configurations. It also showed that as a proximal stabilizer, the upper trapezius muscle had a greater activity in unfastening cycles. The kinetic and physiological responses demonstrated that unfastening fasteners, which has been neglected in the literature, have the potential to increase risk for musculoskeletal disorders and should be considered in ergonomics assessment in the workplace. PMID- 20349389 TI - Validity assessment of self-reported construction tasks. AB - This study assessed agreement between workers' and observers' daily estimates of exposure to construction work tasks. The ultimate aim was to develop a valid method and instrument for the collection of self-reported data on duration of exposure to a priori identified work tasks for use in characterizing exposure in settings with substantial task variability. Forty-nine shop workers and 52 construction site sheet metal workers were observed for up to 3 full workdays. Observers sampled approximately 25% of each worker's day, recording the work performed from a prespecified list of tasks. Each participant completed a daily questionnaire, indicating the tasks he or she performed that day and time spent on each task. Shop workers tended to specialize in particular tasks, while at the construction site, the workers' tasks reflected substantial day-to-day variability. Agreement between worker and observer estimates was generally better for major shop tasks (with intraclass correlation coefficients [ICCs] ranging from 0.52 to 0.85), than for major construction site tasks (with ICCs ranging from 0.36 to 0.64). Workers tended to overestimate the amount of time spent at tasks of longer duration and to underestimate time spent at short-duration tasks. Rank order analysis of time spent on task revealed fairly high agreement. Agreement was acceptable for shop-based work, which has less day-to-day variability than construction site work. Overall, however, the data suggest that, for highly variable work, the use of task as the unit of exposure does not improve recall over assessment approaches focusing on questions about posture and material handling. PMID- 20349390 TI - The role of religion in shaping sexual frequency and satisfaction: evidence from married and unmarried older adults. AB - This study assesses the role of religion in influencing sexual frequency and satisfaction among older married adults and sexual activity among older unmarried adults. The study proposes and tests several hypotheses about the relationship between religion and sex among these two groups of older Americans, using nationally representative data from the National Social Life, Health, and Aging Project. Results suggest that among married older adults, religion is largely unrelated with sexual frequency and satisfaction, although religious integration in daily life shares a weak, but positive, association with pleasure from sex. For unmarried adults, such religious integration exhibits a negative association with having had sex in the last year among women, but not among men. PMID- 20349391 TI - When your errors make me lose or win: event-related potentials to observed errors of cooperators and competitors. AB - Monitoring one's own errors is a fundamental ability in terms of guiding and improving behavior, with specific neural substrates in the anterior cingulate cortex (ACC). Similarly, we can monitor others' actions and learn by observing their errors. The mirror neuron system may subserve the formation of shared representations for self-generated and observed actions, and recent research suggests that monitoring mechanisms also react to errors made by others. However, it remains unknown how these responses are modified when interpersonal context implies different goals for the actor and the observer. To investigate whether differences in social context can influence brain response to observed action errors, we manipulated competition vs. cooperation between two participants taking turns in a go/no-go task. Event-related potentials simultaneously recorded from both participants showed a typical negativity over frontocentral regions to self-generated errors, irrespective of interpersonal context, but early differential responses to other-generated errors only during cooperation, with sources in precuneus and medial premotor areas. Competition produced a distinct error-related negativity in ACC at later latencies. We conclude that error monitoring for others' actions depends on their congruence with personal goals, and recruits brain systems involved in self-referential processing specifically during cooperation. PMID- 20349392 TI - Women's retirement and self-assessed well-being: an analysis of three measures of well-being among recent and long-term retirees relative to homemakers. AB - Focusing on women from the U.S. over 60 years old in 2006, this study analyzed the relationship between retirement and three subjective measures of well-being: depressive symptoms, financial worries, and health. Drawing on the life course perspective and the heterogeneity of women's labor force experiences, this study contrasted the well-being of recent retirees with those who self-identified as homemakers (n = 1695) and long-term retirees with homemakers (n = 2012). Findings indicated that being a recent retiree was associated with more favorable reports of health and that being a long-term retiree was more favorably associated with accounts of all three outcome measures relative to homemakers. Thus, despite the major role change they experienced, findings support the notion that participating in the paid labor force may have been a protective factor with regard to self-assessed well-being. PMID- 20349393 TI - Mental health and interpersonal factors associated with HIV-related risk behaviors among non-institutionalized female injection drug users who are also sex workers in China. AB - Female injecting drug users who are sex workers (IDUFSWs) are an important bridge population in HIV transmission. Few studies have investigated the associations between mental health, interpersonal problems, and HIV-related risk behaviors among injecting drug users who are sex workers. A total of 234 non institutionalized injecting drug users who are sex workers were recruited using the snowball method. Multiple logistic regression was used for data analysis. A high prevalence of mental health (depression, hopelessness, pessimism) and interpersonal (lack of social support and submissive gender power) problems was reported. Optimism and social support were negatively associated with inconsistent condom use during sex work in the last six months (adjusted odds ratios [AOR] = 0.62-0.86); positive associations were observed for depression, hopelessness, pessimism, and gender power (AOR = 1.17 to 1.68). Injecting with others' used syringes in the last six months was negatively associated with social support (AOR = 0.75) and positively associated with hopelessness and gender power (AOR = 1.13-1.27). In two summary models using all significant independent variables as candidates, optimism was negatively (OR = 0.62) and submissive gender powers were positively (OR = 1.67) associated with inconsistent condom use during sex work; submissive gender power was positively associated with injecting with others' used syringes (OR = 1.38). HIV interventions targeting mental health and interpersonal problems are needed among injecting drug users who are sex workers. PMID- 20349394 TI - Breast cancer knowledge and screening behaviors of the female teachers. AB - Breast cancer is the most frequently occurring cancer in women. The objective of this study was to determine the level of knowledge about risk factors for breast cancer and screening behaviors among 468 female teachers who work in Sivas, Turkey. In this cross-sectional survey, a self-administered, structured questionnaire was used for data collection. Up to one-half (52.4%) of the teachers thought that they had enough knowledge about breast cancer. The sources of that information were television (59.0%), newspapers (48.9%), and health professionals (24.1%); 58.5% of the teachers had a sufficient knowledge level about breast cancer risk factors. The most frequently reported risk factor was family history of breast cancer (94.9%), followed by getting older, high fat diet and having a first child at a late age (68.6%, 51.7%, and 45.1%, respectively). No significant differences were found in knowledge by age groups, having breast related complaints, teaching experience, or marital status. Among the teachers, 43.9% had performed breast self-examination; yet only 10.5% of them performed it monthly. Only 22.3% of the teachers reported having at least one clinical breast examination. Among the 136 women over the age of forty years, only 37.5% had had at least one mammogram. A significant association was noted between level of knowledge about breast cancer risk factors and use of breast self-examination. Also, being married and having breast-related complaints were significantly related to practicing clinical breast-examination and mammography. This study revealed a relatively low awareness about the knowledge and practice of screening methods among teachers. The relatively low rates of breast self-examination, clinical breast-examination, and mammography practiced by this group of teachers are of concern and suggest that increased awareness of these methods, their value, and how they should be conducted is needed. PMID- 20349395 TI - Problematic social support, family functioning, and subjective well-being in women with rheumatoid arthritis. AB - The purpose of this study was to examine the relationship of problematic social support and family functioning to measures of subjective well-being in a sample of women with rheumatoid arthritis. Seventy-three women with rheumatoid arthritis completed questionnaires that assessed problematic support (i.e., negative support, unavailability of emotional support), family functioning, and subjective well-being (i.e., life satisfaction and the absence of negative affect or depressive symptoms). Pearson product moment correlation coefficients and hierarchical multivariable regression analyses were conducted. The latter analyses controlled for age, length of time since diagnosis, education, income, pain and fatigue-two prominent symptoms of rheumatoid arthritis. The two measures of problematic support were significantly inversely related to family functioning (p < 0.01 and p < 0.001) and life satisfaction (p = 0.02 and p < 0.001), but were not significantly related to each other. Family functioning was positively related to life satisfaction (p < 0.001) and inversely related to negative affect (p < 0.001) and depressive symptoms (p < 0.001). In multiple regression analyses higher symptom severity, greater problematic support, and lower family functioning were associated with depressive symptoms (p < 0.001) and negative affect (p < 0.001), while higher family functioning and a decrease in symptom severity were associated with life satisfaction (p < 0.001), above and beyond demographic variables and length of time since diagnosis. Subjective well-being in women with rheumatoid arthritis is related to perceptions of family functioning and the amount and type of support received from others, above and beyond the pain and fatigue that characterizes rheumatoid arthritis and is negatively associated with well-being. PMID- 20349396 TI - ADHD among a cohort of ethnic minority women. AB - Attention deficit-hyperactivity disorder has focused primarily on Caucasian boys and men and resulted in limited insight about the experiences of attention deficit-hyperactivity disorder among women from an ethnically diverse background. This descriptive qualitative study explored the experience of 16 women diagnosed with attention deficit-hyperactivity disorder who were also engaged in their academic pursuits. Three themes emerged: (i) internalized chaos, (ii) cultivation of self-understanding, and (iii) commitment to building capacity. Comorbid psychological disorders (e.g., major depression and anxiety) among women with attention deficit-hyperactivity disorder were associated with increased impairment. Broader criteria that demonstrate equitable assessment and recognition of attention deficit-hyperactivity disorder symptoms for both genders are requisite to promote effective interventions and recovery. PMID- 20349397 TI - Women bound to be active (years 3 and 4): can a book club help women overcome barriers to physical activity and improve self-worth? AB - Little progress has been made toward increasing physical activity in women. This study aimed to determine if an 8-month theory-based book club intervention (Women Bound to Be Active) was effective in increasing: (a) self-worth, (b) benefits relative to barriers to physical activity, and (c) physical activity in women (n = 51). Findings suggested a book club was effective for improving: self-worth, the benefits relative to barriers to physical activity, and possibly participation in physical activity. This is an innovative model to help women become more active and learn skills that may enable them to be active on their own long after a physical activity program has ended. PMID- 20349398 TI - [The safety of metrological control of applanation tonometers by technical investigations on transfer standards]. AB - BACKGROUND: According to the German medical devices act and German ordinance on operators of medical devices, human eye tonometers have to be retested every two years. Independent verification laboratories carry out the metrological controls for tonometers which are used by ophthalmogists. Applanation tonometers are frequently used for the accurate measurement of intraocular pressure. For metrological controls these measurement devices are retested by means of test devices (transfer standards) used by verification offices and by private test agencies. PROCEDURE AND METHOD: 25 test devices for applanation tonometers (15 cross-beam balances and 10 force transducer devices), applied for metrological controls by verification offices and by private test agencies, were checked by means of comparative measurements with regard to their quality of measurement and their handling. An applanation tonometer of the type AT 870 (manufacturer: Haag Streit, Switzerland) served as reference device. Within a measurement range from 9.81 mN to 78.45 mN, upward and downward measurements were performed for the mechanical force of applanation tonometers and for the determination of the reverse span. RESULTS: The investigations for all test devices of applanation tonometers show the compliance within permissible error limits in the observed measuring range for the reverse span with the tonometer AT 870. Some instruments exceed the permissible error limits for test devices for up- and downward force measurements. A comparison concerning the measuring accuracy of two different types of test devices (cross-beam balance and force transducer device) shows that the force transducers tend to have smaller measurement uncertainties. CONCLUSION: The high metrological demands on test devices for applanation tonometers for the measurement of mechanical force, a prerequisite for accurate calibration and adjustment of this tonometer type, require much experience and special training of the operator handling these standards, in order to minimize subjective error sources. Schoolings with practical trainings for user are recommended to minimize these errors. At least every three years the test devices have to be maintained and recalibrated, in order to guarantee proper function and accuracy of the measurement. PMID- 20349399 TI - [Photodynamic therapy with verteporfin in occult choroidal neovascularization in age-related macular degeneration]. AB - OBJECTIVE: We investigated retrospectively the clinical outcome of photodynamic therapy (PDT) with verteporfin (Visudyne) in patients with exudative age-related macular degeneration (ARMD) and subfoveal occult choroidal neovascularization (OCN). METHODS: 77 consecutive patients (90 eyes) with OCN were retrospectively analysed using a standardised protocol. It included best corrected visual acuity (BCVA) pre- and post-PDT, greatest linear dimension of OCN (GLD), ophthalmoscopic findings, optical coherence tomography (OCT), fundus photography and fluorescein angiography (FAG). The findings were descriptively analysed by Spearman rank correlation and cross-tabulation. RESULTS: Age ranged from 52 to 92 years (median: 79 years). 7 (8 %) of 90 PDT eyes gained > or = 2 lines, 67 (74 %) eyes stabilised with +/- 1 line. 17 eyes (18 %) showed a deterioration with loss of > or = 2 lines. BCVA of all cases was pre-PDT 0.33 (+/- 0.2), post-PDT 0.27 (+/- 0.2, p < 0.05), in the improvement group pre-PDT 0.4, post-PDT 0.7 in the stable cases pre-/post-PDT 0.3 and in the deterioration group pre-PDT 0.4 and post-PDT 0.2. GLD of all cases was pre-PDT 3.91 mm (minimum: 0.76 mm, maximum: 5.43 mm). From 86 eyes with OCT follow-up of at least 3 months 51 (60 %) had dry macula after last PDT and 35 (40 %) persistent macular edema (ME) in OCT. In 21 eyes (23 %) with leakage of fluorescein after last PDT, treatment was terminated. 10 eyes (47 %) had retinal angiomatous proliferation stage III, of these, 6 eyes presented with retinochoroidal anastomoses. 4 eyes (18 %) showed after PDT retinochoroidal anastomoses, 2 (10 %) vitreomacular traction in epiretinal membrane of the macula, 2 (10 %) had a tear of the retinal pigment epithelium, 1 (5 %) eye had a gain of GLD > 7200 microm, in 1 eye (5 %) BCVA was < 0.05 and in 1 eye (5 %) treatment was stopped at request of the patient. CONCLUSIONS: According to our study PDT might be helpful in the treatment of OCN in ARMD patients for stabilisation but not for improvement of BCVA. Results from large multicentre studies show that concerning BCVA ranibizumab (Lucentis) is superior to PDT in OCN. Further studies are required to investigate the outcome of combined therapy with PDT and VEGF inhibitors for reducing the number of treatments or the number of recurrences of choroidal neovascularisation. PMID- 20349400 TI - [Haemoglobin oxygenation of retinal vessels in branch retinal artery occlusions over time and correlation with clinical outcome]. AB - OBJECTIVE: Purpose of these study was the evaluation of a new method for the measurement of haemoglobin oxygenation in retinal vessels. Patients with branch retinal artery occlusion have been measured before and after a rheological therapy. METHODS: The haemoglobin oxygenation in retinal vessels was measured by the "oxygen module" (Imedos GmbH, Jena, Germany) which uses a special filter (transmission at 548 and 610 nm, band width 10 nm) in the illumination path of a fundus camera. Fundus images were acquired by a colour CCD camera and specific software was used for vessel tracking and calculation of their haemoglobin oxygen saturation. 11 patients with branch retinal artery occlusions, average age 63.4 +/- 11.7 years were investigated at time of diagnosis and at the 5th day of a rheological and intraocular pressure reduction therapy. RESULTS: 10 out of 11 patients have shown an increase of haemoglobin oxygenation over time (on average from 73 +/- 16 % to 87 +/- 11 %). This increase was statistically significant (p < 0.05, Wilcoxon test). Non-affected retinal areas have also shown an increase of haemoglobin oxygenation. The visual acuity improved by one line. This increase in visual acuity was, however, not statistically significant. CONCLUSIONS: We observed an increase of the arterial haemoglobin oxygenation. One possible reason of the improvement of the haemoglobin oxygenation by the therapy may be an increase of the rheological properties of the blood. All patients showed an increase or at least a stabilisation of their visual acuity. Retinal vessel oximetry might be used as an additional parameter in the follow-up of retinal artery occlusion. PMID- 20349401 TI - [Home mechanical ventilation]. PMID- 20349402 TI - [Stereotactic high precision body radiotherapy]. PMID- 20349403 TI - Recall and bias of retrieving gene expression microarray datasets through PubMed identifiers. AB - BACKGROUND: The ability to locate publicly available gene expression microarray datasets effectively and efficiently facilitates the reuse of these potentially valuable resources. Centralized biomedical databases allow users to query dataset metadata descriptions, but these annotations are often too sparse and diverse to allow complex and accurate queries. In this study we examined the ability of PubMed article identifiers to locate publicly available gene expression microarray datasets, and investigated whether the retrieved datasets were representative of publicly available datasets found through statements of data sharing in the associated research articles. RESULTS: In a recent article, Ochsner and colleagues identified 397 studies that had generated gene expression microarray data. Their search of the full text of each publication for statements of data sharing revealed 203 publicly available datasets, including 179 in the Gene Expression Omnibus (GEO) or ArrayExpress databases. Our scripted search of GEO and ArrayExpress for PubMed identifiers of the same 397 studies returned 160 datasets, including six not found by the original search for data sharing statements. As a proportion of datasets found by either method, the search for data sharing statements identified 91.4% of the 209 publicly available datasets, compared to only 76.6% found by our search carried out using PubMed identifiers. Searching GEO or ArrayExpress alone retrieved 63.2% and 46.9% of all available datasets, respectively. There was no difference in the type of datasets found by PubMed identifier searches in terms of research theme or the technology used. However, the studies identified were more likely to have larger sample sizes, were more frequently cited, and published in higher impact journals. CONCLUSIONS: Searching database entries using PubMed identifiers can identify the majority of publicly available datasets, but caution is required when this method is used to collect data for policy evaluation since studies in low impact journals are disproportionately excluded. We urge authors of all datasets to complete the citation fields for their dataset submissions once publication details are known, thereby ensuring their work has maximum visibility and can contribute to subsequent studies. PMID- 20349405 TI - The effect of n-3 fatty acids on levels of methylarginines in patients with end stage renal disease. AB - BACKGROUND: Patients with end-stage renal disease (ESRD) have a very high mortality mainly caused by cardiovascular disease (CVD). It has been suggested that plasma concentrations of asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor, are markedly elevated in patients with ESRD. Elevation of ADMA is linked to CVD and an adverse prognosis. Supplementation with n-3 fatty acids has previously been shown to prevent CVD, but there is very little data regarding the effect of n-3 fatty acids on levels of ADMA. METHODS: Patients with ESRD and documented CVD were randomized to treatment with 1.7 g of n-3 fatty acids (n=103, 34% women) or olive oil (n=103, 38% women) for three months. ADMA, symmetric dimethyl arginine (SDMA), L-arginine, and the relative content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in serum phospholipids were measured before and after treatment. RESULTS: ADMA was normally distributed with a mean value of 0.56+/-0.13 micromol/L (range 0.21 1.01) and only 14/206 (6.8 %) had elevated levels of ADMA. SDMA was generally elevated with a mean value of 1.88+/-0.64 micromol/L (range 0.67-4.56). Supplementation with n-3 fatty acids for three months did not change plasma levels of ADMA, SDMA or L-arginine. CONCLUSIONS: The present data do not support a beneficial effect of n-3 fatty acids on methylarginines in patients with ESRD. PMID- 20349404 TI - Biodegradation of porous calcium phosphate scaffolds in an ectopic bone formation model studied by X-ray computed microtomograph. AB - Three types of ceramic scaffolds with different composition and structure [namely synthetic 100% hydroxyapatite (HA; Engipore), synthetic calcium phosphate multiphase biomaterial containing 67% silicon stabilized tricalcium phosphate (Si TCP; Skelite) and natural bone mineral derived scaffolds (Bio-oss)] were seeded with mesenchymal stem cells (MSC) and ectopically implanted for 8 and 16 weeks in immunodeficient mice. X-ray synchrotron radiation microtomography was used to derive 3D structural information on the same scaffolds both before and after implantation. Meaningful images and morphometric parameters such as scaffold and bone volume fraction, mean thickness and thickness distribution of the different phases as a function of the implantation time, were obtained. The used imaging algorithms allowed a direct comparison and registration of the 3D structure before and after implantation of the same sub-volume of a given scaffold. In this way it was possible to directly monitor the tissue engineered bone growth and the complete or partial degradation of the scaffold. Further, the detailed kinetics studies on Skelite scaffolds implanted for different length of times from 3 days to 24 weeks, revealed in the X-ray absorption histograms two separate peaks associated to HA and TCP. It was therefore possible to observe that the progressive degradation of the Skelite scaffolds was mainly due to the resorption of TCP. The different saturation times in the tissue engineered bone growth and in the TCP resorption confirmed that the bone growth was not limited the scaffold regions that were resorbed but continued in the inward direction with respect to the pore surface. PMID- 20349406 TI - ACE2 and angiotensin 1-7 are increased in a human model of cardiovascular hyporeactivity: pathophysiological implications. AB - BACKGROUND: ACE and ACE2 produce angiotensin II (Ang II), a vasopressor that induces cardiovascular remodeling, and Ang 1-7, a vasodilator with an antiremodeling effect. While Ang 1-7 has antiarrhythmic properties, at higher concentration it may induce ventricular tachycardia and sudden death. ACE2, therefore, may play an essential role in blood pressure homeostasis, in the long term complications of hypertension (cardiovascular remodeling), and in the induction of cardiac electric abnormalities. This study evaluated the levels of ACE2 and Ang 1-7 in Bartter's/Gitelman's patients (BS/GS) who have elevated Ang II and endogenous blockade of Ang II type 1 receptor signaling compared with healthy subjects (C) and essential hypertensives (EH). BS/ GS patients were also considered because of their predisposition to cardiac arrhythmias, which has yet to be completely clarified. METHODS: Mononuclear cell ACE2 and Ang 1-7 were evaluated using western blot. RESULTS: One-way ANOVA showed that ACE2 and Ang 1-7 levels were significantly different between the three groups (p=0.0074 and p=0.0001, respectively). Post-hoc analysis (Tukey's HSD) showed that both ACE2 (1.59+/-0.63) and Ang1-7 (2.26+/-1.18) were significantly elevated in BS/GS compared with either C (0.98+/-0.45; p=0.008; 1.12+/-0.48, p=0.002, respectively) or EH (1.06+/-0.24; p=0.043; 0.72+/-0.28; p=0.0001, respectively). ACE2 and Ang 1 7 directly correlated only in BS/GS (r=0.91, p<0.0003). CONCLUSIONS: The elevated ACE2 and Ang 1-7 in BS/ GS patients mirror those in hypertensives and are in line with the clinical, hemodynamic and pathophysiological characteristics of BS/GS, likely contributing to them. In consideration of the clinical picture of these syndromes, the opposite of hypertension, the results of this study further strengthen the importance of the ACE2/Ang 1-7 system in the regulation of vascular tone and cardiovascular biology. PMID- 20349407 TI - Effect of phlorizin on SGLT2 expression in the kidney of diabetic rats. AB - BACKGROUND: The purpose of our study was to determine whether increased SGLT2 expression in the kidney of diabetic rats was associated with the development of hypertension and to investigate the effect of phlorizin (P) on blood pressure and SGLT2 expression in diabetic rats. METHODS: The animals were divided into two groups: Control (C) and streptozotocin-induced diabetic (D) rats were used to evaluate SGLT2 activity in brush border membrane vesicles (BBMV) using a rapid filtration technique. Others animals were divided into two groups: Normal (NSD) or high salt diet (4%)(HSD), and subdivided in four groups: C, C+P, D, D+P. Systolic blood pressure (SBP) was recorded for 30 days by the use of a telemetric system and at day 30 urine samples (24 h) were collected to evaluate renal function and SGLT2 expression in the renal cortex. RESULTS: At day 30, diabetic animals with NSD or HSD exhibited hyperglycemia, lower body weight, glycosuria, diuresis, decrease natriuresis, increased SBP values and SGLT2 expression. In diabetic rats, phlorizin treatment decreased hyperglycemia and prevented development of hypertension, decreased SGLT2 activity in BBMV but did not modify SGLT2 expression. CONCLUSIONS: In conclusion, SGLT2 inhibition prevented the development of hypertension in diabetic rats as well as hyperglycemia, suggesting a hypertensive mechanism associated with SGLT2 activity and the likelihood that increased SGLT2 expression may be associated with progression of diabetic renal complications. PMID- 20349408 TI - Warfarin: to use or not to use in chronic kidney disease patients? AB - Is the risk of major bleeding the only reason to be concerned about oral anticoagulant therapy in chronic kidney disease patients? We consider another potential adverse effect of long-term Coumadin use in chronic kidney disease patients as comparably devastating: the threat of inducing creeping vascular calcification. PMID- 20349409 TI - H1N1 infection and the kidney in critically ill patients. AB - BACKGROUND: Acute renal failure due to viral infections is rare. We assessed the development of acute kidney injury (AKI) in critically compromised patients due to the H1N1 influenza virus. METHODS: All patients with a PCR -confirmed diagnosis of H1N1 influenza infection admitted to the intensive care unit between May and July 2009 were retrospectively studied. Thereafter, the risk factors associated with the development of acute renal injury, the requirements of acute hemodialysis (HD) and death were analyzed. RESULTS: Twenty-two patients with H1N1 pneumonia were included: age: 52.91 +/- 18.89 years; gender: males 11 (50%); chronic airway disease: 9 (41%); oncohematological disease: 8 (36.7%); cardiovascular disease 5 (22.7%); chronic renal insufficiency: 4 (18.2%); obesity 3 (13.6%); concomitant pregnancy: 2 (9.1%); diabetes mellitus: 2 (9.1%); previous influenza A vaccination: 9 (41%). All patients received oseltamivir within 48 hours of presumed diagnosis. Seventeen patients (77.3%) developed fever initially. Six patients (27.3%) required noninvasive ventilation assistance and 15 patients (68.2%) received invasive ventilatory support. Mean days on mechanical respiratory assistance: 11 +/- 10.35. Arterial partial pressure of oxygen/fraction of inspired oxygen ratio: 140.11 +/- 83.03 mmHg. Inotropic drugs were administered to 15 patients (68.2%). Fourteen patients (63.6%) developed AKI. Mean highest creatinine levels: 2.74 +/- 2.83 mg/dl. Four patients (18.2%) needed renal replacement therapy with a mean duration of 15 +/- 12 days. Six patients (42.9%) recovered renal function. AKI was associated with pregnancy, immunosuppression, high APAC HE, SOFA and MURRA Y scores, and less time on mechanical ventilation assistance, hemodynamical instability and thrombocytopenia. HD requirements were associated with elevated SOFA scores (12.25 +/- 1.75 vs. 6.22 +/- 0.8, p<0.05), elevated creatine phosphokinase (933 +/- 436.6 vs. 189.9 +/- 79.3 U/L, p<0.05) and alanine transferase levels (843.3 +/- 778.8 vs. 85.33 +/- 17.4 U/L, p<0.05). Twelve patients died (54.6%), 10 of whom had acute renal failure (83.3%) and 3 had been on acute HD (25%). Mortality was associated with higher APACHE, SOFA and Murray scores, a higher oseltamivir dose (253.1 +/- 25.8 vs. 183.8 +/- 27.6 mg, p<0.05), lower oxygen inspired fraction/alveolar pressure ratio (99.3 +/- 12.2 vs. 196.3 +/- 33.9 mmHg, p<0.01), thrombocytopenia (88966 +/- 22977 vs. 141200 +/- 17282 mm3, p<0.05), hypoalbuminemia (1.82 +/- 0.1 vs. 2.61 +/- 0.2 g/dl, p<0.01), acute renal failure (10 vs. 4, p<0.05), oligoanuria (5 vs. 0, p<0.05) and lack of recovery of renal function (2 vs. 4, p<0.01). Three out of 4 (75%) of the hemodialyzed patients died. CONCLUSIONS: In the critically ill due to H1N1 pneumonia, renal insufficiency was a frequent complication, demanding renal replacement therapy in 18% of cases. The need for HD was associated with an elevated risk of death. Mortality was mainly associated with multiple organ failure, oligoanuria, acute renal injury and a lack of recovery of renal function. PMID- 20349410 TI - Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates. AB - BACKGROUND: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. METHODS: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. RESULTS: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). CONCLUSION: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing. PMID- 20349411 TI - Contrast-induced acute kidney injury: how should at-risk patients be identified and managed? AB - Contrast-induced acute kidney injury (CIAKI) refers to a sudden deterioration in renal function associated with the use of iodinated contrast media. CIAKI can lead to increased morbidity and mortality. Risk of CIAKI is low in the general population but increased in patients with risk factors, which include chronic kidney disease (particularly secondary to diabetes mellitus) and advanced age. Screening for risk factors and implementation of prevention practices in at-risk patients is recommended. Patients at risk of CIAKI because of chronic kidney disease can be identified by serum creatinine measurement, although, preferably, this should be applied to estimate glomerular filtration rate; screening questionnaires or risk scoring can also identify at-risk patients. Current best practice calls for intravenous periprocedural volume expansion in at-risk patients, but this is not practical in all clinical settings. No pharmacological approach has been demonstrated to offer consistent protection. Volume/dose of contrast agent should be the lowest needed to achieve a diagnostic result. The use of iso-osmolar contrast media is recommended for high-risk patients, because recent controlled clinical trials in coronary procedure settings have shown a lower nephrotoxicity of iodixanol, as compared with several low-osmolar contrast agents. However, additional studies involving a larger selection of iso- and low osmolar contrast media are needed, particularly with intravenous use for computed tomography scans, if their use in this patient population is to be optimized. PMID- 20349412 TI - Impact of calcium, phosphate, PTH abnormalities and management on mortality in hemodialysis: results from the RISCAVID study. AB - BACKGROUND: Despite substantial progress in medical care, the mortality rate remains unacceptably high in dialysis patients. Evidence suggests that bone mineral dismetabolism (CKD-MBD) might contribute to this burden of death. However, to date only a few papers have investigated the clinical relevance of serum mineral derangements and the impact of different therapeutic strategies on mortality in a homogeneous cohort of south European dialysis patients. METHODS: The RISCAVID study was a prospective, observational study in which all patients receiving hemodialysis (HD) in the north-western region of Toscany in June 2004 were enrolled (N=757) and followed up for 24 months. RESULTS: At study entry, only 71 (9%) patients of the entire study cohort exhibited an optimal control of serum phosphorous (Pi), calcium (Ca), calciumX-phosphorous product (CAXPi) and intact parathyroidhormone (iPTH) according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical guidelines. Despite a similar prevalence, the severity of CKD-MBD appeared different to the results reported in the USA. Interestingly, none of the serum biomarkers or number of serum biomarkers within KDOQI targets was independently associated with all-cause and cardiovascular (CV) mortality. Among treatments, Sevelamer was the only drug independently associated with lower all-cause and cardiovascular mortality (p<0.001). CONCLUSION: The RISCAVID study highlights the difficulty of controlling bone mineral metabolism in HD patients and lends support to the hypothesis that a carefully chosen phosphate binder might impact survival in HD patients. PMID- 20349413 TI - Renal epithelioid angiomyolipoma: a malignant disease. AB - BACKGROUND: Renal angiomyolipomas are recognized as clonal neoplasms with clonal chromosomal aberrations and a common progenitor cell, the perivascular epithelial cell (PEC). The epithelioid variant is a recently identified entity, characterized by predominance of PEC and a unique morphologic and immunohistochemical profile. There is accumulating evidence suggesting that renal epithelioid angiomyolipoma (REA) is a malignant disease. METHODS: We searched the literature for descriptions of clinical behavior of REA. A Pubmed search was performed using the following key words: angiomyolipoma, epithelioid, perivascular epithelial cell or/and renal tumors. We reviewed a case of fatal REA at our institution. A pathologist reviewed slides to confirm the diagnosis. RESULTS: Upon review of 140 articles, 37 eligible articles were found including 10 articles describing the clinical course of REA. Almost all of the patients described, for whom there was a follow-up available, died of neoplastic progression of the disease, with liver, lung and bone metastases. Four cases were reclassified after retrospective pathology review, and they were fatal. Three of these had been misdiagnosed as renal cell carcinoma (RCC), while 1 was diagnosed as classic angiomyolipoma. CONCLUSION: Unlike commonly benign classic angiomyolipoma, REA behaves aggressively. It is crucial for the clinician to be aware of and identify this epithelioid variant as a malignant disease. It should be carefully differentiated from RCC. Resection alone may not be curative, and adjuvant therapy should be considered. A multimodality treatment approach needs to be explored for this newly recognized malignant variant renal angiomyolipoma. PMID- 20349414 TI - Markers of inflammation and oxidative stress in peritoneal dialysis: a comparison between high and low peritoneal transporters. AB - INTRODUCTION: High transport status is reported to be associated with increased mortality in peritoneal dialysis (PD). It has been hypothesized that this might be a result of a state of chronic inflammation and increased oxidative stress. We performed this pilot study to explore this hypothesis. METHODS: Based on the standard peritoneal equilibration test, PD patients were divided in two transporter groups: LOW (Low + Low average) and HIGH (High + High Average). Markers of inflammation and oxidative stress were compared between the two groups, including C-reactive protein (CRP), plasma apoptogenic potential, monocyte HLA DR expression, Advanced Oxidative Protein Products (AOPP) and reactive carbonyl residues (RCO). RESULTS: Of 42 patients (34 male/8 female) studied, 8 patients were LOW and 34 were HIGH transporters. Median values of CRP (1.39 vs. 0.62 mg/L), plasma apoptogenic potential (15 vs. 14.5%), AOPP (118.36 vs. 113.86 micromol/L) and RCO (1.72 vs. 1.13 nmol/mg protein) were similar among LOW and HIGH transporters. However HIGH transporters had significantly lower monocyte HLA DR expression (mean fluorescent intensity (MFI) -197.89 vs. 124.98 units, p=0.02) compared with LOW transporters. CONCLUSIONS: Stable chronic PD patients with high peritoneal transport status have reduced monocyte HLA-DR expression, a biomarker of increased risk for infections. This could potentially contribute to a higher risk of mortality in this group. PMID- 20349415 TI - Phosphate binders, cardiovascular calcifications and mortality: do we need another survival study with sevelamer? AB - In chronic renal failure patients, hyperphosphatemia has been associated with vascular calcifications and increased cardiovascular morbidity and mortality. In vitro observations have shown that calcium and phosphate independently and synergistically induce calcifications in human vascular smooth muscle cells, suggesting an important role for both in the calcification process. Because non calcium phosphate binders reduce serum phosphate without increasing the calcium load, as is the case with calcium-based phosphate binders, it has been speculated that treatment with sevelamer leads to less vascular calcification and better survival in chronic kidney disease. Although the use of sevelamer may slow the progression of vascular calcifications compared with calcium-based phosphate binders, the relationship of this surrogate marker with patients' cardiovascular mortality and survival is far from certain. To resolve this uncertainty and to determine the most cost-effective way to treat hyperphosphatemia in patients with end-stage renal disease, another randomized study analyzing mortality comparing sevelamer with calcium phosphate binders should be undertaken. PMID- 20349416 TI - Differences in ischemia-modified albumin levels between end stage renal disease patients and the normal population. AB - INTRODUCTION: Conventional biomarkers suffer from the drawback of being elevated in chronic renal failure even in the absence of myocardial ischemia. Ischemia modified albumin (IMA) is a new biomarker proposed for the diagnosis of myocardial ischemia. This study was performed with the primary aim of determining IMA levels in patients with end stage renal disease (ESRD). The secondary aim of the study was to determine the impact of hemodialysis (HD), HD speed, and hemoglobin (Hb) levels on IMA levels. METHODS: The study was conducted with 108 ESRD patients entering HD and 30 healthy volunteers. The serum IMA levels of ESRD patients were compared with the post-HD levels and also with healthy individuals. The interaction between Hb levels and HD treatment and the IMA levels were tested by using the Generalized Linear Model for repeated measurements. RESULTS: The IMA levels of ESRD patients, both pre- and post-HD, were significantly higher than those of the control group. The baseline IMA levels of "low" and "high Hb groups" were not significantly different. Hb level modifies the effect of HD treatment on IMA concentration in ESRD patients. Furthermore, post-HD levels of IMA were increased at a lower dialysis speed. CONCLUSIONS: Both pre- and post-dialysis IMA levels are higher in ESRD patients entering HD than in healthy individuals. Anemia is an effect-modifier for the effect of HD treatment on IMA levels in ESRD patients. PMID- 20349417 TI - Urinary balantidiasis: diagnosis at a glance by urine sediment examination. AB - A 56-year-old Caucasian man with non-Hodgkin's lymphoma, who had previously been treated with prolonged intensive chemotherapy, was hospitalized for an acute and reversible kidney injury of multifactorial origin. The urinary sediment examination, performed daily, demonstrated the presence of renal tubular cells and renal tubular cell casts. Surprisingly, it also showed the presence of trophozoites of the protozoan Balantidium coli, which were identified on the basis of its characteristic morphology and rapid movements across the slide, and transient leukocyturia. The patient was asymptomatic, his medical history was negative for gastrointestinal disease, and no Balantidium coli was found in the feces. In spite of this, due to the previous chemotherapy, the patient was treated with oral metrodinazole. Only one other case with Balantidium coli in the urine sediment has been described so far and this paper stresses the importance of the examination of the urinary sediment. PMID- 20349418 TI - Chronic kidney disease and cancer: a troubling connection. AB - Chronic kidney disease (CKD) and cancer are connected in a number of ways in both directions: cancer can cause CKD either directly or indirectly through the adverse effects of therapies; CKD may, conversely, be a risk factor for cancer; and both may be associated because they share common risk factors, often toxins. In this review, we briefly address the issue of paraneoplastic nephropathies as well as that of toxin-related cancers and CKD, including analgesic and aristolochic acid nephropathies. We then focus on the links between the various stages of CKD and cancer incidence, and critically examine major epidemiologic surveys in the field. Compared with the general population, kidney transplant recipients have a threefold to fourfold increase in overall cancer risk, and relative risks higher than 3 for about 20 specific tumors, most, but not all, of which are known or suspected to be caused by viral agents. After dialysis, cancer risk increases 10% to 80% according to studies, with relative risks significantly higher than in the general population, for about 10 cancer sites. There is emerging evidence for an excess risk of cancer in patients in early CKD stages. PMID- 20349419 TI - Aging or comorbid conditions - what is the main cause of kidney damage? AB - BACKGROUND: Chronic kidney disease (CKD) is widespread in the general population. It is generally accepted that worsening renal function is common with aging. However, the question still remains whether it is caused by the natural process of aging or whether coexisting chronic diseases and comorbid conditions contribute to deteriorating renal function. METHODS: The frequency of albuminuria the marker of early kidney damage-was evaluated according to different coexisting conditions in younger (18/64 years old, n=2,074) and elderly (=65 years old, n=395) participants of the Polish study PolNef on early detection of CKD. Multivariate logistic regression was performed to identify associations between elevated levels of albuminuria, age and coexisting conditions. RESULTS: 12% of the younger group demonstrated albuminuria compared to 18% of the elderly. Independent predictors of detecting an elevated level of albuminuria for the whole examined population were male gender (2.48, 1.59-3.88), hypertension ineffectively treated (1.8, 1.34-2.4), diabetes (1.67, 1.11-2.49), and age (1.56, 0.97-2.52) at border levels of significance. Moreover, elevated levels of albuminuria occurred more frequently in the obese elderly group (1.89, 0.98-3.63, p=0.058). The following predictors were found based on gender: for men, hypertension regardless of efficacy of treatment, diabetes, smoking, and age at border level of significance, in contrast to women who had the sole predictor of ineffectively treated hypertension. CONCLUSIONS: The influence of aging alone on kidney damage is not evident. Moreover, it is different in males and females. Hypertension is the only coexisting comorbid condition contributing to kidney damage in both males and females. Advanced age together with comorbid conditions is more harmful to the kidney in males. PMID- 20349420 TI - Transplant tolerance: progress and challenges. AB - Organ transplantation has proven to be an effective therapeutic for a wide variety of disease states, but the chronic immunosuppression required for allograft survival increases the risk for infection and neoplasia. In the past 50 years, a wealth of experimental data has been accumulated relating to strategies to preserve function and prolong graft survival. These strategies operate by inducing peripheral or central tolerance to the allograft, with protocols based on regulatory T cell (Treg) induction as the most promising ones. However, as these protocols move into the clinic, there is recognition that little is known as to their efficacy when confronted with the human immune system: preexisting memory T cells and "heterologous immunity" in antigen-experienced humans but not in immunologically naive rodents, infections and early activation of innate immune response and the related inflammation-induced cytokine milieu that inhibit Treg activity while augmenting the T effector response, all pose significant barriers to tolerance induction. A better understanding of the cellular and molecular mechanisms by which memory T cells and innate immunity modulate transplant tolerance and detailed immunologic studies of the rare "spontaneously tolerant" patients may lead to development of combined strategies that target and modulate the immune system at multiple levels. PMID- 20349421 TI - The management of left ventricular systolic dysfunction in patients with advanced chronic kidney disease. AB - BACKGROUND: Left ventricular systolic dysfunction (LVSD) is frequently observed in patients with advanced chronic kidney disease (CKD) and its presence is associated with a poor prognosis. Renin-angiotensin system (RAS) inhibition and beta-adrenergic blockade are the cornerstones of medical management for LVSD. Current guidelines advocate that CKD patients with advanced LVSD should receive these therapies. The extent to which these recommendations are followed is unclear. The goal of this study was to evaluate practice patterns for LVSD management across the spectrum of patients with advanced CKD, and to determine the rate of utilization of recommended therapies for LVSD. METHODS: This cross sectional study encompassed all long-term dialysis patients (n=299) and patients with advanced pre-dialysis CKD who were followed in a multidisciplinary clinic (n=176) at a tertiary care center in Toronto, Canada. Echocardiographic and pharmacotherapy data were sought for each patient. In patients with moderate severe LVSD (ejection fraction <40%), we evaluated the extent to which optimal pharmacotherapy, defined as the receipt of a beta-adrenergic receptor blocker and a RAS inhibitor (an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker), was applied. We then sought to identify factors to explain the usage of these therapies. RESULTS: Of the 475 eligible patients, 387 had echocardiographic data available for analysis. Among these individuals, 34 (8.8%) had moderate-severe LVSD, of whom 23 (67.7%) were receiving optimal therapy. Non receipt of optimal therapy could not be explained by hypotension, hyperkalemia, known drug sensitivities, or pill burden. CONCLUSIONS: Approximately one-third of patients with advanced CKD and significant LVSD were not receiving optimal pharmacotherapy, in the absence of known contraindication or intolerance. Identifying and overcoming barriers to care will be crucial in order to enhance the management of this high-risk population. PMID- 20349422 TI - The effect of uremia and hemodialysis on caspase-1 and caspase-3 activity in neutrophils. AB - BACKGROUND: Neutrophils in uremia maintain chronic inflammation, which contributes to malnutrition and immunity disorders. The influence of hemodialysis on the life span of neutrophils is unclear, although many authors postulate its apoptotic effect. Erythropoietin (EPO) is an antiapoptotic factor for various cells. We investigated factors possibly interfering in apoptosis of neutrophils in hemodialysis (HD) patients, such as HD session, parathormone (PTH), dose of EPO, inflammation and nutrition. SUBJECTS AND METHODS: Twenty HD patients and ten healthy controls were donors of neutrophils. We evaluated caspase-1 and caspase-3 activities, related to apoptosis of neutrophils, before and after a 4-hour HD session with cuprophane or polysulphone dialyzer. We measured serum concentrations of C-reactive protein, cholesterol, albumin, prealbumin and transferrin. Time of dialysis treatment, PTH level and dose of EPO were also evaluated. RESULTS: We observed a significant increase in caspase-1 activity and decrease in caspase-3 activity in neutrophils after HD with cuprophane, but not with polysulphone. Caspase-1 activity correlated positively with EPO dose and negatively with PTH level. Caspase-3 correlated negatively with the time of dialysis treatment. No correlation between caspase activity and markers of inflammation or nutrition was noticed. CONCLUSIONS: The results suggest that HD with bioincompatible cuprophane may prolong the life span of neutrophils due to the intense inflammatory reaction and high activity of caspase-1. Time of dialysis treatment, PTH level and EPO dose potentially influence the life span of neutrophils. PTH seems to have a proapoptotic effect of neutrophils, while EPO is an antiapoptotic factor. PMID- 20349423 TI - Can omeprazole reduce the incidence of hypercalcemia in dialysis patients using calcium containing phosphate binders? AB - INTRODUCTION: Calcium absorption from the bowel is known to depend upon gastric acidity. We chose to investigate whether the use of omeprazole could reduce the incidence of hypercalcemia in dialysis patients who could not afford expensive non-calciumbased phosphate binders. METHODS: 26 hemodialysis patients at the Hypertension, Nephrology, Dialysis, and Transplantation Clinic in Opelika, Alabama (USA) with refractory hypercalcemia for at least 3 months prior to the study who were unable to afford non-calcium-based binders were treated with 20 mg of omeprazole a day for three months and then compared to 27 similar patients who were taking non-calcium-based binders. RESULTS: While there was a trend towards lower serum calcium levels and phosphate binder dosages in the omeprazole group (particularly with the calcium carbonate binders as opposed to the calcium acetate binders), there was no statistical difference in any variable in either controls or the omeprazole group from pre-study period. CONCLUSIONS: While theoretically advantageous, we found that omeprazole had little clinical benefit in reducing hypercalcemia in a population who are unable to afford non-calcium based binders; however, further studies may be warranted. PMID- 20349424 TI - Role of renal sympathetic nervous system in the control of renal potassium handling. AB - BACKGROUND: It is well established that renal sympathetic nerves are primarily involved in renal sodium and water regulation. However, the relationship between renal sympathetic nerve activity (RSNA) and renal potassium handling is not extensively known. The present study was performed to investigate the role of the renal sympathetic nervous system in the regulation of tubular potassium reabsorption and secretion. METHODS: Male Sprague Dawley (SD) rats (each group, n=6) were fasted overnight, anesthetized with pentobarbital sodium (60 mg/kg intraperitoneal), denervated by application of phenol to the left renal artery and maintained on an intravenous infusion of saline for 2 hours. During this period, 6 urine and plasma samples were collected at 20-minute intervals to study kidney function parameters. RESULTS: In denervated rats, there were significantly higher (all p<0.05 vs. innervated control) urine flow rate (UFR), glomerular filtration rate (GFR), absolute sodium excretion (U(Na)V), fractional sodium excretion (FE(N)a), absolute potassium excretion (U(K)V), fractional potassium excretion (FE(K)) and urinary sodium to urinary potassium ratio (U(Na)/U(K)). No appreciable differences were seen in the mean arterial pressure (MAP) and plasma sodium (P(Na)) between denervated and innervated SD rats. However, plasma potassium (P(K)) levels were significantly lower (p<0.05) in denervated rats as compared with innervated counterparts. CONCLUSIONS: There is a possible involvement of renal nerves in the regulation of renal potassium handling. This effect is largely attributable to a direct action of renal sympathetic nerves on the renal tubular segments. PMID- 20349425 TI - Perspectives in renal disease progression: the endothelium as a treatment target in chronic kidney disease. AB - The endothelial cell layer is the "guardian" of molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function: e.g., control of vasomotor tone and permeability. Cardiovascular risk factors such as hypertension may cause endothelial dysfunction and even disintegration, finally resulting in small vessel disappearance (vascular rarefaction) and tissue hypoxia. In patients with chronic kidney diseases (CKD), ongoing endothelial damage in the capillary system of the renal medulla and accompanying vascular rarefaction are thought to be central processes toward progressive kidney damage. In this respect, reduced nitric oxide synthesis by endothelial cells due to accumulation of endogenous inhibitors of the nitric oxide synthase such as asymmetric dimethylarginine (ADMA) has been accused of accelerating progression. Thus, reducing ADMA blood levels could be potentially beneficial in clinical trials aimed at reducing the loss of kidney function in CKD patients. Another molecule coming into the focus of cardiovascular medicine is erythropoietin (EPO). Recent experimental studies have shown that EPO - beside its effect on hematopoietic cells - protects endothelial cell function and integrity and has vasculoprotective properties. EPO could therefore prevent renal tissue injury and CKD progression due to vascular rarefaction and hypoxia. PMID- 20349426 TI - Renal beta2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection. AB - BACKGROUND: Renal infections elevate the risk of sepsis and are important causes of septic shock and multiple organ failure. The objective of the present study was to test the hypothesis that renal beta(2)-adrenoceptor (beta(2)-AR) blockade impairs the organ response to renal infection induced by Escherichia coli (E. coli) administration. METHODS: A rat model of renal infection was induced using an intraparenchymal injection of E. coli into the right kidney, either alone or in rats pre-treated with the beta(2)-AR antagonist, ICI 118,551 (3.14 microg/kg). RESULTS: The rat renal infection model significantly raised growth-related oncogene/keratinocyte-derived cytokine, granulocyte-macrophage colony-stimulating factor and cAMP levels in the right kidney and caused an elevation in serum cytokines and nitric oxide (NO), whereas creatinine clearance rate (Ccr) was maintained over the course of the infection. Conversely, treatment of the rat model with the beta(2)-AR antagonist resulted in a decrease of Ccr and serum NO, greater increases in serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6, associated with an elevation of the right renal TNF-alpha and cannabinoid-1 receptor, and a reduction of the right renal Gsalpha and cAMP levels. Moreover, the inhibition of beta(2)-AR activation impaired the clearance of endotoxins from the kidney and was associated with a raised mortality rate. CONCLUSIONS: The blockade of a renal beta(2)-AR signaling cascade aggravates inflammatory responses in the infected kidney, changes serum levels of cytokines, NO, and noradrenaline, and leads to renal dysfunction and a higher rate of mortality. PMID- 20349427 TI - New pathways to renal damage: role of ADMA in retarding renal disease progression. AB - In recent years, increasing evidence has been found that chronic kidney disease (CKD) is a strong cardiovascular risk factor, and therefore, the concept of cardiorenal association is well recognized. One possible factor that could explain this link seems to be endothelial dysfunction. It is widely recognized that endothelial dysfunction plays important roles in both the initiation and progression of atherosclerosis. In addition, we have come to understand that endothelial dysfunction may be a causative factor for proteinuria and/or progression of CKD. Asymmetric dimethylarginine (ADMA) is a naturally occurring L arginine analogue found in plasma and various types of tissues, acting as an endogenous nitric oxide synthase inhibitor in vivo. Plasma levels of ADMA are elevated in patients with CKD and have been found to be a strong biomarker or predictor for future cardiovascular disease (CVD) as well as the progression of renal injury. These findings suggest that elevation of ADMA-mediated endothelial dysfunction may be a missing link between CVD and CKD. In this review, we discuss the biology of ADMA, especially focusing on its role in the progression of CKD. PMID- 20349428 TI - Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease. AB - BACKGROUND: Mast cells (MCs) might play a pathogenetic role in renal fibrosis. Tryptase is a marker for activated MCs. Little is known about tryptase levels in the chronic renal disease population. METHODS: We examined serum MC tryptase concentrations in relation to specific laboratory abnormalities in 153 outpatients with chronic kidney disease (CKD) and in 35 hemodialysis (HD) patients. RESULTS: Here we found that tryptase mean values were higher in men than in women (12.4 +/- 7.6 microg/L vs. 10.2 +/- 8.4 microg/L; p<0.05). Tryptase levels were increased in CKD stages 4 and 5 and in HD patients, versus CKD stages 1 and 2: 12.7 +/- 7.3 microg/L, 13.8 +/- 7.8 microg/L, 15 +/- 8.9 microg/L vs. 6.7 +/- 5.1 microg/L (p<0.01). In univariate analysis, in the conservative treatment CKD population, tryptase was positively correlated with urea, creatinine, potassium, uric acid, phosphorus, parathyroid hormone, homocysteine, fibrinogen and proteinuria (p<0.01); tryptase was negatively correlated with calcium, albumin, creatinine clearance, estimated glomerular filtration rate (by abbreviated MDRD equation) and urine creatinine (p<0.01). In HD patients, the only significative correlation found was with systolic blood pressure and diastolic blood pressure (p<0.01). No significant correlations were found between tryptase and other parameters such as albumin, glucose, hemoglobin, leukocytes, immunoglobulins or C-reactive protein. Multiple regression analysis showed estimated glomerular filtration rate and proteinuria to be independent determinants of tryptase. CONCLUSIONS: This is the first study to determine that tryptase levels increase with higher degrees of kidney dysfunction. The association with markers of diminished renal function suggests impaired metabolism or a negative effect of inflammation on glomerular filtration rate. Further studies are required to ascertain the clinical implications of these findings. PMID- 20349429 TI - Multifunctional hybrid fabrics with thermally stable superhydrophobicity. PMID- 20349430 TI - Gecko-inspired surfaces: a path to strong and reversible dry adhesives. AB - The amazing adhesion of gecko pads to almost any kind of surfaces has inspired a very active research direction over the last decade: the investigation of how geckos achieve this feat and how this knowledge can be turned into new strategies to reversibly join surfaces. This article reviews the fabrication approaches used so far for the creation of micro- and nanostructured fibrillar surfaces with adhesive properties. In the light of the pertinent contact mechanics, the adhesive properties are presented and discussed. The decisive design parameters are fiber radius and aspect ratio, tilt angle, hierarchical arrangement and the effect of the backing layer. Also first responsive systems that allow thermal switching between nonadhesive and adhesive states are described. These structures show a high potential of application, providing the remaining issues of robustness, reliability, and large-area manufacture can be solved. PMID- 20349433 TI - Chemistry at play in materials science: the centennial celebration of chemistry at Peking University. PMID- 20349435 TI - Plasma-assisted approaches in inorganic nanostructure fabrication. AB - Plasma is a unique medium for chemical reactions and materials preparations, which also finds its application in the current tide of nanostructure fabrication. Although plasma-assisted approaches have been long used in thin-film deposition and the top-down scheme of micro-/nanofabrication, fabrication of zero and one-dimensional inorganic nanostructures through the bottom-up scheme is a relatively new focus of plasma application. In this article, recent plasma assisted techniques in inorganic zero- and one-dimensional nanostructure fabrication are reviewed, which includes four categories of plasma-assisted approaches: plasma-enhanced chemical vapor deposition, thermal plasma sintering with liquid/solid feeding, thermal plasma evaporation and condensation, and plasma treatment of solids. The special effects and the advantages of plasmas on nanostructure fabrication are illustrated with examples, emphasizing on the understandings and ideas for controlling the growth, structure, and properties during plasma-assisted fabrications. This Review provides insight into the utilization of the special properties of plasmas in nanostructure fabrication. PMID- 20349438 TI - Formate-based magnetic metal-organic frameworks templated by protonated amines. AB - A systematic study has been carried out on the 3d divalent metal formate 3D magnetic frameworks templated by protonated amines, and the achievements have revealed that metal formate frameworks are very malleable, and their structures depend on the size, shape, charge, and hydrogen bonding geometries of the templating cations. Six kinds of metal formate frameworks have been created. They are chiral frameworks with a (4(9) . 6(6)) topology, perovskite ones with a (4(12) . 6(3)) topology, bi-nodal frameworks of (4(12) . 6(3))(4(9) . 6(6))(n) (n = 1, 2, 3) topologies, and porous diamond frameworks with 6(6) topology. These materials display promising and abundant magnetic, dielectric, porous, and optical properties and the possible combination of them. Therefore, they are of great interest for the study of molecule-based materials. It has been demonstrated that formate, being the smallest and simplest carboxylate, cheap and with low toxicity, thus more biocompatible and environmentally friendly, and having been more or less ignored, will find an important role in the construction of molecule-based materials and provide new materials with interesting properties. PMID- 20349440 TI - Research on small genomes: implications for synthetic biology. AB - Synthetic genomics is a new field of research in which small DNA pieces are assembled in a series of steps into whole genomes. The highly reduced genomes of host-associated bacteria are now being used as models for de novo synthesis of small genomes in the laboratory. Bacteria with the smallest genomes identified in nature provide nutrients to their hosts, such as amino acids, co-factors and vitamins. Comparative genomics of these bacteria enables predictions to be made about the gene sets required for core cellular functions and the associated metabolic network for the biosynthesis of host-selected compounds. Synthetic biology may ultimately enable researchers to make customized cell-specific organelles for the production and delivery of drugs to humans and domestic animals. Synthetic genomics may also become the method of choice for functional analyses of genes and genomes from bacteria that cannot be cultivated in the laboratory. PMID- 20349441 TI - A powerful toolkit for synthetic biology: Over 3.8 billion years of evolution. AB - The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio-engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine-tuning through evolution is suggested. PMID- 20349442 TI - Numbers on the edges: a simplified and scalable method for quantifying the gene regulation function. AB - The gene regulation function (GRF) provides an operational description of a promoter behavior as a function of the concentration of one of its transcriptional regulators. Behind this apparently trivial definition lies a central concept in biological control: the GRF provides the input/output relationship of each edge in a transcriptional network, independently from the molecular interactions involved. Here we discuss how existing methods allow direct measurement of the GRF, and how several trade-offs between scalability and accuracy have hindered its application to relatively large networks. We discuss the theoretical and technical requirements for obtaining the GRF. Based on these requirements, we introduce a simplified and easily scalable method that is able to capture the significant parameters of the GRF. The GRF is able to predict the behavior of a simple genetic circuit, illustrating how addressing the quantitative nature of gene regulation substantially increases our comprehension on the mechanisms of gene control. PMID- 20349447 TI - Encoded multichromophore response for simultaneous label-free detection. AB - The self-assembly of molecularly precise nanostructures is widely expected to form the basis of future high-speed integrated circuits, but the technologies suitable for such circuits are not well understood. In this work, DNA self assembly is used to create molecular logic circuits that can selectively identify specific biomolecules in solution by encoding the optical response of near-field coupled arrangements of chromophores. The resulting circuits can detect label free, femtomole quantities of multiple proteins, DNA oligomers, and small fragments of RNA in solution via ensemble optical measurements. This method, which is capable of creating multiple logic-gate-sensor pairs on a 2 x 80 x 80-nm DNA grid, is a step toward more sophisticated nanoscale logic circuits capable of interfacing computers with biological processes. PMID- 20349448 TI - Comparison of one-step and two-step meta-analysis models using individual patient data. AB - The problem of combining information from separate trials is a key consideration when performing a meta-analysis or planning a multicentre trial. Although there is a considerable journal literature on meta-analysis based on individual patient data (IPD), i.e. a one-step IPD meta-analysis, versus analysis based on summary data, i.e. a two-step IPD meta-analysis, recent articles in the medical literature indicate that there is still confusion and uncertainty as to the validity of an analysis based on aggregate data. In this study, we address one of the central statistical issues by considering the estimation of a linear function of the mean, based on linear models for summary data and for IPD. The summary data from a trial is assumed to comprise the best linear unbiased estimator, or maximum likelihood estimator of the parameter, along with its covariance matrix. The setup, which allows for the presence of random effects and covariates in the model, is quite general and includes many of the commonly employed models, for example, linear models with fixed treatment effects and fixed or random trial effects. For this general model, we derive a condition under which the one-step and two-step IPD meta-analysis estimators coincide, extending earlier work considerably. The implications of this result for the specific models mentioned above are illustrated in detail, both theoretically and in terms of two real data sets, and the roles of balance and heterogeneity are highlighted. Our analysis also shows that when covariates are present, which is typically the case, the two estimators coincide only under extra simplifying assumptions, which are somewhat unrealistic in practice. PMID- 20349446 TI - Three-dimensional fabrication at small size scales. AB - Despite the fact that we live in a 3D world and macroscale engineering is 3D, conventional submillimeter-scale engineering is inherently 2D. New fabrication and patterning strategies are needed to enable truly 3D-engineered structures at small size scales. Here, strategies that have been developed over the past two decades that seek to enable such millimeter to nanoscale 3D fabrication and patterning are reviewed. A focus is the strategy of self-assembly, specifically in a biologically inspired, more deterministic form, known as self-folding. Self folding methods can leverage the strengths of lithography to enable the construction of precisely patterned 3D structures and "smart" components. This self-assembly approach is compared with other 3D fabrication paradigms, and its advantages and disadvantages are discussed. PMID- 20349449 TI - Pretreatment of Siam weed stem by several chemical methods for increasing the enzymatic digestibility. AB - Siam weed [Chromolaena odorata (L.) King & Robinson], an invasive exotic weed in China, was proposed as a feedstock for bioethanol production. This would be a promising way of using for an invasive weed that needs management and control. It was found that the glucan content of the weed stem was similar to that of sugarcane bagasse, but higher than those of corn stover and wheat straw. Several chemical pretreatment methods were applied to the weed stem to increase its enzymatic digestibility. Mild sulfuric acid (<120 degrees C) or alkali pretreatment did not markedly increase the enzymatic digestibility. However, peracetic acid (PAA) pretreatment dramatically enhanced the enzymatic hydrolysis of the weed stem. Compared to some other common agricultural residues, the weed stem was more difficult to pretreat and digest by cellulase. Fourier transform infrared (FTIR) spectra analysis indicated that the cellulose-related bands became more intensive after pretreatment, especially for PAA-pretreated samples. According to X-ray diffraction spectra, the biomass solids had higher crystallinity indices after pretreatment, although these indices were similar for all of the pretreated samples. PMID- 20349450 TI - Immobilization conditions of ketoreductase on enantioselective reduction in a gas solid bioreactor. AB - The immobilization conditions of commercial ketoreductase for continuous enantioselective reduction in the gas-phase reaction were investigated with respect to the immobilization efficiency (residual activity and protein loading) and the gas-phase reaction efficiency (initial reaction rate, half-life, and enantioselectivity). For the analyses, ketoreductase was first immobilized by physical deposition on glass supports and the reduction of 2-butanone to (S)-2 butanol with the concomitant regeneration of NADH by 2-propanol was used as a model reaction. The optimal conditions of enzyme immobilization were obtained using an absolute pressure of 100 hPa for drying, a pH between 6.5 and 7.0, and a buffer concentration of 50 mM. The buffer concentration in particular had a strong effect on both the enzyme activity and enantioselectivity. Under optimal immobilization conditions, the thermostability of ketoreductase in the gas-phase system was enhanced compared to the aqueous-phase system, while the enantioselectivity was successfully maintained at a level identical to that of the native enzyme. These results indicate that the gas-phase reaction has a great potential for industrial production of chiral compounds, but requires careful optimization of immobilization conditions for the reaction to progress effectively. PMID- 20349452 TI - On-chip cell culture on a microarray of extracellular matrix with surface modification of poly(dimethylsiloxane). AB - Microfluidic cell culture chips allow to perform assays of small-volume samples rapidly and reproducibly. Most of these chips are made of poly(dimethylsiloxane) (PDMS), which is a flexible, durable, transparent and inexpensive polymer that can be easily applied to fabrication of microstructures by photolithography and replica molding. However, not many cells are able to grow on unmodified PDMS because the cells need appropriate scaffolds on the surface. Here we report surface modification of a PDMS substrate with a microarray of extracellular matrix (ECM) for on-chip cell culture. The ECM proteins collagen and fibronectin were covalently immobilized on an 8 x 8 microarray format by micropatterned UV induced graft polymerization through a photomask and dehydration-condensation reaction through a microfabricated stencil. Identical spots of ECMs were successfully formed and the geometry of the spots accurately corresponded to the micropattern of the photomask and stencil. We demonstrate the culture of CHO-K1 cells on the ECM microarray chip. Cells proliferated on the fibronectin spots during the 2-day culture. PMID- 20349451 TI - Ethanol production from cellulosic materials using cellulase-expressing yeast. AB - We demonstrate direct ethanol fermentation from amorphous cellulose using cellulase-co-expressing yeast. Endoglucanases (EG) and cellobiohydrolases (CBH) from Trichoderma reesei, and beta-glucosidases (BGL) from Aspergillus aculeatus were integrated into genomes of the yeast strain Saccharomyces cerevisiae MT8-1. BGL was displayed on the yeast cell surface and both EG and CBH were secreted or displayed on the cell surface. All enzymes were successfully expressed on the cell surface or in culture supernatants in their active forms, and cellulose degradation was increased 3- to 5-fold by co-expressing EG and CBH. Direct ethanol fermentation from 10 g/L phosphoric acid swollen cellulose (PASC) was also carried out using EG-, CBH-, and BGL-co-expressing yeast. The ethanol yield was 2.1 g/L for EG-, CBH-, and BGL-displaying yeast, which was higher than that of EG- and CBH-secreting yeast (1.6 g/L ethanol). Our results show that cell surface display is more suitable for direct ethanol fermentation from cellulose. PMID- 20349455 TI - Editorial: From beta-catenin and signaling to biotech. PMID- 20349458 TI - 'Interactome' analysis: a step forward in proteomics research. PMID- 20349459 TI - Report and recommendation of a workshop on education and training for measurement, monitoring, modelling and control (M3C) in biochemical engineering. PMID- 20349460 TI - High-throughput RNAi screening to dissect cellular pathways: a how-to guide. AB - RNA interference (RNAi) has become a powerful tool to dissect cellular pathways and characterize gene functions. The availability of genome-wide RNAi libraries for various model organisms and mammalian cells has enabled high-throughput RNAi screenings. These RNAi screens successfully identified key components that had previously been missed in classical forward genetic screening approaches and allowed the assessment of combined loss-of-function phenotypes. Crucially, the quality of RNAi screening results depends on quantitative assays and the choice of the right biological context. In this review, we provide an overview on the design and application of high-throughput RNAi screens as well as data analysis and candidate validation strategies. PMID- 20349461 TI - Real-time PCR-based determination of gene copy numbers in Pichia pastoris. AB - Pichia pastoris is a preferred host for heterologous protein production. Expression cassettes are usually integrated into the genome of this methylotrophic yeast. This manuscript describes a method for fast and reliable gene copy number determinations for P. pastoris expression strains. We believe that gene copy number determinations are important for all researchers working with P. pastoris and also many other research groups using similar gene integration techniques for the transformation of other yeasts. The described method uses real-time PCR to quantify the integrated expression cassettes. Similar methods were employed previously for other host systems such as animal and plant cells but no such method comparing different detection methods and describing details for yeast analysis by quantitative PCR is known to us, especially for methylotrophic yeasts such as P. pastoris. Neglecting gene copy numbers can easily lead to false interpretations of experimental results from codon optimization or promoter studies and co-expression of helper proteins as demonstrated in an application example, which is also described here. PMID- 20349462 TI - Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: proof-of-concept of efficacy. AB - Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training). Robust hindlimb stepping with weight-bearing capabilities was induced with the tri-therapy but not with clinically relevant doses of these compounds administered separately. These results provide evidence suggesting that this drug combination may be ideally suited to constitute a first in-class therapy (CPG activator) for locomotor activity induction in chronic SCI individuals, given that efficacy was shown using commercially available brain permeable small molecules, already known as safe for the treatment of various neurological indications. PMID- 20349464 TI - Disulfide bond cleavage: a redox reaction without electron transfer. AB - By using Car-Parrinello molecular dynamics (CPMD) simulations we have simulated a mechanically induced redox reaction. Previous single-molecule atomic force microscopy (AFM) experiments demonstrated that the reduction of disulfide bonds in proteins with the weak reducing agent dithiothreitol depends on a mechanical destabilization of the breaking bond. With reactive molecular dynamics simulations the single steps of the reaction mechanism can be elucidated and the motion of the electrons can be monitored. The simulations show that the redox reaction consists of the heterolytic cleavage of the S--S bond followed by a sequence of proton transfers. PMID- 20349465 TI - A time-resolved spectroscopic study of the bichromophoric phototrigger 3',5' dimethoxybenzoin diethyl phosphate: interaction between the two chromophores determines the reaction pathway. AB - 3',5'-Dimethoxybenzoin (DMB) is a bichromophoric system that has widespread application as a highly efficient photoremovable protecting group (PRPG) for the release of diverse functional groups. The photodeprotection of DMB phototriggers is remarkably clean, and is accompanied by the formation of a biologically benign cyclization product, 3',5'-dimethoxybenzofuran (DMBF). The underlying mechanism of the DMB deprotection and cyclization has, however, until now remained unclear. Femtosecond transient absorption (fs-TA) spectroscopy and nanosecond time resolved resonance Raman (ns-TR(3)) spectroscopy were employed to detect the transient species directly, and examine the dynamic transformations involved in the primary photoreactions for DMB diethyl phosphate (DMBDP) in acetonitrile (CH(3)CN). To assess the electronic character and the role played by the individual sub-chromophore, that is, the benzoyl, and the di-meta-methoxybenzylic moieties, for the DMBDP deprotection, comparative fs-TA measurements were also carried out for the reference compounds diethyl phosphate acetophenone (DPAP), and 3',5'-dimethoxybenzylic diethyl phosphate (DMBnDP) in the same solvent. Comparison of the fs-TA spectra reveals that the photoexcited DMBDP exhibits distinctly different spectral character and dynamic evolution from those of the reference compounds. This fact, combined with the related steady-state spectral and density functional theoretical results, strongly suggests the presence in DMBDP of a significant interaction between the two sub-chromophores, and that this interaction plays a governing role in determining the nature of the photoexcitation and the reaction channel of the subsequent photophysical and photochemical transformations. The ns-TR(3) results and their correlation with the fs-TA spectra and dynamics provide evidence for a novel concerted deprotection-cyclization mechanism for DMBDP in CH(3)CN. By monitoring the direct generation of the transient DMBF product, the cyclization time constant was determined unequivocally to be approximately 1 ns. This indicates that there is little relevance for the long-lived intermediates (>10 ns) in giving the DMBF product, and excludes the stepwise mechanism proposed in the literature as the major pathway for the DMB cyclization reaction. This work provides important new insights into the origin of the 3',5'-dimethoxy substitution effect for the DMB photodeprotection. It also helps to clarify the many different views presented in previous mechanistic studies of the DMB PRPGs. In addition to this, our fs-TA results on the reference compound DMBnDP in CH(3)CN provide the first direct observation (to the best of our knowledge) showing the predominance of a prompt (approximately 2 ps) heterolytic bond cleavage after photoexcitation of meta methoxybenzylic compounds. This provides insight into the long-term controversies about the photoinitiated dissociation mode of related substituted benzylic compounds. PMID- 20349466 TI - Electron attachment to hydrated oligonucleotide dimers: guanylyl-3',5'-cytidine and cytidylyl-3',5'-guanosine. AB - The dinucleoside phosphate deoxycytidylyl-3',5'-deoxyguanosine (dCpdG) and deoxyguanylyl-3',5'-deoxycytidine (dGpdC) systems are among the largest to be studied by reliable theoretical methods. Exploring electron attachment to these subunits of DNA single strands provides significant progress toward definitive predictions of the electron affinities of DNA single strands. The adiabatic electron affinities of the oligonucleotides are found to be sequence dependent. Deoxycytidine (dC) on the 5' end, dCpdG, has larger adiabatic electron affinity (AEA, 0.90 eV) than dC on the 3' end of the oligomer (dGpdC, 0.66 eV). The geometric features, molecular orbital analyses, and charge distribution studies for the radical anions of the cytidine-containing oligonucleotides demonstrate that the excess electron in these anionic systems is dominantly located on the cytosine nucleobase moiety. The pi-stacking interaction between nucleobases G and C seems unlikely to improve the electron-capturing ability of the oligonucleotide dimers. The influence of the neighboring base on the electron-capturing ability of cytosine should be attributed to the intensified proton accepting-donating interaction between the bases. The present investigation demonstrates that the vertical detachment energies (VDEs) of the radical anions of the oligonucleotides dGpdC and dCpdG are significantly larger than those of the corresponding nucleotides. Consequently, reactions with low activation barriers, such as those for O-C sigma bond and N-glycosidic bond breakage, might be expected for the radical anions of the guanosine-cytosine mixed oligonucleotides. PMID- 20349468 TI - Structural characterisation of the Li argyrodites Li7PS6 and Li7PSe6 and their solid solutions: quantification of site preferences by MAS-NMR spectroscopy. AB - Li(7)PS(6) and Li(7)PSe(6) belong to a class of new solids that exhibit high Li(+) mobility. A series of quaternary solid solutions Li(7)PS(6-x)Se(x) (0 < or = x < or = 6) were characterised by X-ray crystallography and magic-angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. The high-temperature (HT) modifications were studied by single-crystal investigations (both F43m, Z=4, Li(7)PS(6): a=9.993(1) A, Li(7)PSe(6): a=10.475(1) A) and show the typical argyrodite structures with strongly disordered Li atoms. HT-Li(7)PS(6) and HT Li(7)PSe(6) transform reversibly into low-temperature (LT) modifications with ordered Li atoms. X-ray powder diagrams show the structures of LT-Li(7)PS(6) and LT-Li(7)PSe(6) to be closely related to orthorhombic LT-alpha-Cu(7)PSe(6). Single crystals of the LT modifications are not available due to multiple twinning and formation of antiphase domains. The gradual substitution of S by Se shows characteristic site preferences closely connected to the functionalities of the different types of chalcogen atoms (S, Se). High-resolution solid-state (31)P NMR is a powerful method to differentiate quantitatively between the distinct (PS(4 n)Se(n))(3-) local environments. Their population distribution differs significantly from a statistical scenario, revealing a pronounced preference for P-S over P-Se bonding. This preference, shown for the series of LT samples, can be quantified in terms of an equilibrium constant specifying the melt reaction Se(P)+S(2-) <==>S(P)+Se(2-), prior to crystallisation. The (77)Se MAS-NMR spectra reveal that the chalcogen distributions in the second and third coordination sphere of the P atoms are essentially statistical. The number of crystallographically independent Li atoms in both LT modifications was analysed by means of (6)Li{(7)Li} cross polarisation magic angle spinning (CPMAS). PMID- 20349467 TI - CH-directed anion-pi interactions in the crystals of pentafluorobenzyl substituted ammonium and pyridinium salts. AB - Simple pentafluorobenzyl-substituted ammonium and pyridinium salts with different anions can be easily obtained by treatment of the parent amine or pyridine with the respective pentafluorobenzyl halide. Hexafluorophosphate is introduced as the anion by salt metathesis. In the case of the ammonium salt 4, water co crystallisation seems to suppress effective anion-pi interactions of bromide with the electron-deficient aromatic system, whereas with salts 5 and 6 such interactions are observed despite the presence of water. However, due to asymmetric hydrogen-bonding interactions with ammonium side chains, the anion of 5 is located close to the rim of the pentafluorophenyl group (eta(1) interaction). In 6 the CH-anion hydrogen bonding is more symmetric and fixes the anion on top of the ring (eta(6)). A similar structure-controlling effect is observed in case of the 1,4-diazabicyclo[2.2.2]octane derivatives 7. Here the position of the anion (Cl, Br, I) is shifted according to the length of the weak CH-halide interaction. The hexafluorophosphate 7 d reveals that this "non coordinating" anion can be located on top of an aromatic pi system. In the methyl substituted pyridinium salts 9 and 10 different locations of the bromide anions with respect to the pi system are observed. This is due to different conformations of the mono- versus disubstituted pyridine, which leads to different directions of the weak, but structurally important, H(Me)-Br bonds. PMID- 20349469 TI - Lanthanide-catalyst-mediated tandem double intramolecular hydroalkoxylation/cyclization of dialkynyl dialcohols: scope and mechanism. AB - Lanthanide-organic complexes of the general type [Ln{N(SiMe(3))(2)}(3)] (Ln=La, Sm, Y, Lu) serve as effective precatalysts for the rapid, exo-selective, and highly regioselective tandem double intramolecular hydroalkoxylation/cyclization of primary and secondary dialkynyl dialcohols to yield the corresponding bi exocyclic enol ethers. Conversions are highly selective with products distinctly different from those generally produced by conventional transition metal or other catalysts, and the turnover frequencies with some substrates are too large to determine accurately. The rates of terminal alkynl alcohol hydroalkoxylation/cyclization are significantly more rapid than those of internal alkynyl alcohols, arguing that steric demands dominate the cyclization transition state. The hydroalkoxylation/cyclizations of internal dialkynyl dialcohols afford excellent E selectivity. The rate law for dialkynyl dialcohol hydroalkoxylation/cyclization is first-order in [catalyst] and zero-order in [alkynyl alcohol], as is observed for the organolanthanide-catalyzed hydroamination/cyclization of aminoalkenes, aminoalkynes, and aminoallenes, and the intramolecular single-step hydroalkoxylation/cyclization of alkynyl alcohols. An ROH/ROD kinetic isotope effect of 0.82(0.02) is observed for the tandem double hydroalkoxylation/cyclization. These mechanistic data implicate turnover-limiting insertion of C-C unsaturation into the Ln-O bond, involving a highly organized transition state, with subsequent, rapid Ln-C protonolysis. PMID- 20349471 TI - Large porphyrin squares from the self-assembly of meso-triazole-appended L-shaped meso-meso-linked Zn(II)-triporphyrins: synthesis and efficient energy transfer. AB - meso-Triazolyl-appended Zn(II)-porphyrins were readily prepared by Cu(I) catalyzed 1,3-dipolar cycloaddition of benzyl azide to meso-ethynylated Zn(II) porphyrin (click chemistry). In noncoordinating CHCl(3) solvent, spontaneous assembly occurred to form tetrameric array (3)(2) from meso-meso-linked diporphyrins 3, and dodecameric porphyrin squares (4)(4) and (5)(4) from the L shaped meso-meso-linked triporphyrins 4 and 5. The structures of these assemblies were examined by (1)H NMR spectra, absorption spectra, and their gel permeation chromatography (GPC) retention time. Furthermore, the structures of the dodecameric porphyrin squares (4)(4) and (5)(4) were probed by small- and wide angle X-ray scattering (SAXS/WAXS) measurements in solution using a synchrotron source. Excitation-energy migration processes in these assemblies were also investigated in detail by using both steady-state and time-resolved spectroscopic methods, which revealed efficient excited-energy transfer (EET) between the meso meso-linked Zn(II)-porphyrin units that occurred with time constants of 1.5 ps( 1) for (3)(2) and 8.8 ps(-1) for (5)(4). PMID- 20349470 TI - A simple assay for the fluorometric detection of lithium ions in aqueous solution. PMID- 20349472 TI - Organosilyl/-germyl polyoxotungstate hybrids for covalent grafting onto silicon surfaces: towards molecular memories. AB - Organosilyl/-germyl polyoxotungstate hybrids [PW(9)O(34)(tBuSiO)(3)Ge(CH(2))(2)CO(2)H](3-) (1a), [PW(9)O(34)(tBuSiO)(3)Ge(CH(2))(2)CONHCH(2)C[triple bond]CH](3-) (2 a), [PW(11)O(39)Ge(CH(2))(2)CO(2)H](4-) (3a), and [PW(11)O(39)Ge(CH(2))(2)CONHCH(2)C[triple bond]CH](4-) (4a) have been prepared as tetrabutylammonium salts and characterized in solution by multinuclear NMR spectroscopy. The crystal structure of (NBu(4))(3)1a.H(2)O has been determined and the electrochemical behavior of 1a and 2a has been investigated by cyclic voltammetry. Covalent grafting of 2a onto an n-type silicon wafer has been achieved and the electrochemical behavior of the grafted clusters has been investigated. This represents the first example of covalent grafting of Keggin type clusters onto a Si surface and a step towards the realization of POM-based multilevel memory devices. PMID- 20349473 TI - PdCl(2)-catalyzed domino reactions of 2-alkynylbenzaldehydes with indoles: synthesis of fluorescent 5h-benzo[b]carbazol-6-yl ketones. PMID- 20349474 TI - Redox-tuning endohedral fullerene spin states: from the dication to the trianion radical of Sc(3)N@C(80)(CF(3))(2) in five reversible single-electron steps. PMID- 20349475 TI - Rational design of fluorescent bioimaging probes by controlling the aggregation behavior of squaraines: a special effect of ionic liquid pendants. AB - We herein present an effective strategy to create water-soluble fluorescent bioimaging dyes by introducing the imidazolium-based ionic liquid (IL) pendants into a fluorescent skeleton. A new type of water-soluble imidazolium-anchored squaraine dye was synthesized accordingly. The relationship between the aggregate of squaraines and their fluorescent cell imaging application was elucidated in detail. Firstly, the aggregation behavior of squaraines in water solutions could be suppressed by varying the alkyl chain attached to the imidazolium unit. Secondly, the capability of cellular uptake and staining of dyes was also dramatically enhanced upon increasing the length of the paraffinic chain. These squaraine dyes displayed an excellent photostability that could permit real-time fluorescence bioimaging experiments to be monitored over a long time period with constant sample irradiation. Additionally, we designed for the first time an Fe(II)-ion probe on the basis of an attack of the hydroxyl radical to the four membered ring of squaraine. The results demonstrated that the imidazolium anchored squaraines could perform "naked-eye" detection of the Fe(2+) ion over a wide range of other interfering metals in aqueous media. More surprisingly, this process showed a fluorescence "turn-off" and "-on" response through the regeneration of squaraines in cells. PMID- 20349476 TI - Heteroheptacenes with fused thiophene and pyrrole rings. AB - The preparation of conjugated heteroheptacenes using an electrophilic coupling reaction induced by a super acid is reported. The new molecules containing thiophene and/or pyrrole rings are bisbenzo[b,b']thienodithieno[3,2-b:2',3' d]pyrrole, bisbenzo[b,b']thienocyclopenta[2,1-b:3,4-b']dithiophene, and bisthieno[3,2-b]thieno[2,3-f:5,4-f']carbazole. Dithieno[3,2-b:2',3'-d]pyrrole, cyclopenta[2,1-b:3,4-b']dithiophene, and carbazole are used as the aromatic cores. This versatility provides access to molecules with systematically controllable physicochemical properties. Single-crystal X-ray analyses demonstrate that the type and position of the alkyl substituents significantly changes the packing properties of the new molecules. The optical and optoelectronic properties of the heteroheptacenes vary considerably depending on the number and position of the sulfur or nitrogen linkages and reveal the improved environmental stability over their hydrocarbon counterparts. The analysis of the experimental results from UV/Vis absorption/photoluminescence (PL) spectroscopy and cyclic voltammetry were combined with DFT quantum-chemical calculations and compared with other model heteroheptacenes. The results suggest that among the acenes with the same number of fused rings, the thiophene ring fusion inside the skeleton stabilizes both HOMO and LUMO levels more effectively than pyrrole and benzene rings. The present study also shows that the new heteroheptacenes are promising candidates for the construction of electronic materials. PMID- 20349477 TI - Mechanistic exploration of the intramolecular hydroalkoxylation of allenyl alcohols mediated by organolanthanide complexes: a DFT study. PMID- 20349478 TI - Gold sulfide nanoclusters: a unique core-in-cage structure. PMID- 20349479 TI - Gold(I)-mediated silicon-silicon bond metathesis at room temperature. PMID- 20349480 TI - Layered graphene/quantum dots for photovoltaic devices. PMID- 20349481 TI - Genetic engineering of biomolecular scaffolds for the fabrication of organic and metallic nanowires. PMID- 20349482 TI - Three-component reaction using the Bestmann-Ohira reagent: a regioselective synthesis of phosphonyl pyrazole rings. PMID- 20349483 TI - Metal-to-oxide molar volume ratio: the overlooked barrier to solid-state electroreduction and a "green" bypass through recyclable NH4HCO3. PMID- 20349484 TI - Direct measurement of electrical transport through G-quadruplex DNA with mechanically controllable break junction electrodes. PMID- 20349485 TI - Label-free imaging of metal-carbonyl complexes in live cells by Raman microspectroscopy. PMID- 20349486 TI - Clustomesogens: liquid crystal materials containing transition-metal clusters. PMID- 20349488 TI - Selective preparation of 3,4,5-trinitro-1H-pyrazole: a stable all-carbon-nitrated arene. PMID- 20349493 TI - Impact of the C-terminal disulfide bond on the folding and stability of onconase. AB - The two homologous proteins ribonuclease A and onconase fold through conserved initial contacts but differ significantly in their thermodynamic stability. A disulfide bond is located in the folding initiation site of onconase (the C terminal part of the protein molecule) that is missing in ribonuclease A, whereas the other three disulfide bonds of onconase are conserved in ribonuclease A. Consequently, the deletion of this C-terminal disulfide bond (C87-C104) allows the impact of the contacts in this region on the folding of onconase to be studied. We found the C87A/C104A-onconase variant to be less active and less stable than the wild-type protein, whereas the tertiary structure, which was determined by both X-ray crystallography and NMR spectroscopy, was only marginally affected. The folding kinetics of the variant, however, were found to be changed considerably in comparison to wild-type onconase. Proton exchange experiments in combination with two-dimensional NMR spectroscopy revealed differences in the native-state dynamics of the two proteins in the folding initiation site, which are held responsible for the changed folding mechanism. Likewise, the molecular dynamics simulation of the unfolding reaction indicated disparities for both proteins. Our results show that the high stability of onconase is based on the efficient stabilization of the folding initiation site by the C-terminal disulfide bond. The formation of the on-pathway intermediate, which is detectable during the folding of the wild-type protein and promotes the fast and efficient refolding reaction, requires the presence of this covalent bond. PMID- 20349494 TI - Evolution of the channelrhodopsin photocycle model. AB - Many processes in green algae are under control of rhodopsin-type photoreceptors, but only a few have been studied at least in some detail in the past. Up to now, functionally and biochemically only the channelrhodpsins ChR1 and ChR2 are characterized. Thus, this short review reports on channelrhodopsin properties with a strong focus on the knowledge about the photoreaction cycle(s). PMID- 20349496 TI - In situ observation of the emission characteristics of zeolite-hosted silver species during heat treatment. PMID- 20349495 TI - On the compatibility criteria for protein encapsulation inside mesoporous materials. AB - The properties of the enzyme pepsin, relevant to its incorporation inside the channels of mesoporous silica materials in the preparation of bioinorganic hybrids, are highlighted by molecular dynamics simulations of aqueous solutions of the protein under conditions optimal for encapsulation in SBA-15. The protein size, shape, flexibility and surface properties are calculated with the aim of deriving general accessibility/compatibility criteria favouring encapsulation inside mesoporous systems. PMID- 20349497 TI - Direct measure of the tilt angle in de Vries-type liquid crystals through NMR spectroscopy. PMID- 20349498 TI - Prospective validation of a comprehensive in silico hERG model and its applications to commercial compound and drug databases. AB - Ligand-based in silico hERG models were generated for 2 644 compounds using linear discriminant analysis (LDA) and support vector machines (SVM). As a result, the dataset used for the model generation is the largest publicly available (see Supporting Information). Extended connectivity fingerprints (ECFPs) and functional class fingerprints (FCFPs) were used to describe chemical space. All models showed area under curve (AUC) values ranging from 0.89 to 0.94 in a fivefold cross-validation, indicating high model consistency. Models correctly predicted 80 % of an additional, external test set; Y-scrambling was also performed to rule out chance correlation. Additionally models based on patch clamp data and radioligand binding data were generated separately to analyze their predictive ability when compared to combined models. To experimentally validate the models, 50 of the predicted hERG blockers from the Chembridge database and ten of the predicted non-hERG blockers from an in-house compound library were selected for biological evaluation. Out of those 50 predicted hERG blockers, tested at a concentration of 10 microM, 18 compounds showed more than 50 % displacement of [(3)H]astemizole binding to cell membranes expressing the hERG channel. K(i) values of four of the selected binders were determined to be in the micromolar and high nanomolar range (K(i) (VH01)=2.0 microM, K(i) (VH06)=0.15 microM, K(i) (VH19)=1.1 microM and K(i) (VH47)=18 microM). Of these four compounds, VH01 and VH47 showed also a second, even higher affinity binding site with K(i) values of 7.4 nM and 36 nM, respectively. In the case of non-hERG blockers, all ten compounds tested were found to be inactive, showing less than 50 % displacement of [(3)H]astemizole binding at 10 microM. These experimentally validated models were then used to virtually screen commercial compound databases to evaluate whether they contain hERG blockers. 109 784 (23 %) of Chembridge, 133 175 (38 %) of Chemdiv, 111 737 (31 %) of Asinex and 11 116 (18 %) of the Maybridge database were predicted to be hERG blockers by at least two of the models, a prediction which could, for example, be used as a pre-filtering tool for compounds with potential hERG liabilities. PMID- 20349499 TI - Identification of potent and selective human carbonic anhydrase VII (hCA VII) inhibitors. PMID- 20349500 TI - Rh(I)-catalyzed two-component [(5+2)+1] cycloaddition approach toward [5-8-5] ring systems. PMID- 20349506 TI - Recent advances on bioorganic chemistry of plant metabolites controlling nyctinasty. AB - Leguminous plants open their leaves during the daytime and close them at night as if sleeping, a type of movement that follows circadian rhythms, and is known as nyctinastic movement. This phenomenon is controlled by two endogenous bioactive substances that exhibit opposing activities: Leaf-Opening Factor (LOF), which opens the leaves, and Leaf-Closing Factor (LCF), which closes them. The authors have carried out chemical biological research using these bioactive substances as molecular probes in order to clarify the mechanisms of nyctinastic movement. Here, we report on the detection and identification of the target proteins of these compounds using original methodology. PMID- 20349507 TI - Chemical synthesis of homogeneous glycopeptides and glycoproteins. AB - Oligosaccharides linked to proteins are known to play important roles in several biological events. However, oligosaccharides are heterogeneous, which has hindered detailed elucidation of oligosaccharide functions. In order to solve this problem, glycoproteins having homogeneous oligosaccharides have long been required. For this purpose, an efficient preparative method of complex-type oligosaccharides has been investigated from a natural source and this method was found to afford over 24 kinds of diverse complex-type oligosaccharides by use of chemical methods and branch-specific sequential glycosidase digestion. The sufficient amount of homogeneous complex type oligosaccharides obtained enabled us to examine the synthesis of homogeneous glycopeptides as well as glycoproteins by use of solid phase glycopeptide synthetic method and native chemical ligation. This review describes recent progress related to the efficient method of oligosaccharide preparation and synthesis of glycoproteins including bioactive erythropoietin. PMID- 20349508 TI - New strategy in synthetic biology: from enzyme inhibition and natural products synthesis to PET imaging by 6pi-azaelectrocyclization. AB - While elucidating the inhibitory mechanism of a hydrolytic enzyme by aldehyde containing natural products, we discovered a reaction involving a rapid 6pi azaelectrocyclization of azatrienes generated from aldehyde with lysine residues. The electrocyclic reaction of the 1-azatriene system, a cyclization precursor, exhibited a substituent effect. Structure-reactivity studies showed that azaelectrocyclization, which usually proceeds in low yield at high temperatures, produced a quantitative yield in less than 5 min at room temperature. Asymmetric chiral piperidine synthesis and a one-pot library synthesis of pyridines on solid supports were applied to synthesize pyridine/indole alkaloid-type natural products. Additionally, we developed lysine-based labeling of biomolecules based on the rapid 6pi-azaelectrocyclization. Both DOTA as a metal chelating agent (either for MRI, PET, or other radiopharmaceutical purposes, e.g., SPECT with gamma emitters) as well as fluorescent groups were introduced efficiently and selectively into lysine residues within 10 min at concentrations as low as 10(-8) m. The DOTA-labeled somatostatin and glycoproteins were then radiometallated with (68)Ga to observe the receptor-mediated accumulation of somatostatin in pancreatic tissue. Furthermore, microPET visualized the oligosaccharide dependent circulatory residence of glycoproteins for the first time. PMID- 20349509 TI - CE-MS. PMID- 20349510 TI - The first example of MEEKC-ICP-MS coupling and its application for the analysis of anticancer platinum complexes. AB - MEEKC is a powerful electrodriven separation technique with many applications in different disciplines, including medicinal chemistry; however, up to now the coupling to highly sensitive and selective MS detectors was limited due to the ion suppressive effect of the commonly used surfactant SDS. Herein, the first example of the coupling of MEEKC to ICP-MS is presented and an MEEKC method for the separation of Pt(II) and Pt(IV) anticancer drugs and drug candidates was developed. Different compositions of microemulsions were evaluated and the data were compared with those collected with standard ultraviolet/visible (UV/vis) spectroscopy detection. The MEEKC-ICP-MS system was found to be more sensitive than MEEKC-UV/vis and the analysis of UV/vis silent compounds is now achievable. The migration behavior of the Pt(II) and Pt(IV) compounds under investigation is correlated to their different chemical structures. PMID- 20349512 TI - Electrokinetic supercharging-electrospray ionisation-mass spectrometry for separation and on-line preconcentration of hypolipidaemic drugs in water samples. AB - Electrokinetic supercharging, a powerful on-line preconcentration technique in CE, was for the first time hyphenated with ESI-MS for the on-line concentration and separation of five hypolipidaemic drugs. The electrophoretic separation was performed in a co-EOF mode using the EOF reversal agent, hexadimethrine bromide, in ammonium bicarbonate electrolyte, pH 9.00. The ionic strength and the amount of methanol in the buffer were optimised in a multivariate manner using artificial neural networks, with the optimal conditions being 60 mM ammonium bicarbonate containing 60% methanol, providing baseline resolution of the five hypolipidaemics within 20 min. Using electrokinetic supercharging, the sensitivity of the method was improved 1000-fold over a conventional injection under field-amplified sample stacking conditions with LODs of 180 ng/L. This is the first report of the separation of hypolipidaemics by CE. The developed method was validated and then applied to the determination of the target drugs in water samples from Hobart city. PMID- 20349511 TI - CEC-atmospheric pressure ionization MS of pesticides using a surfactant-bound monolithic column. AB - A surfactant bound poly (11-acrylaminoundecanoic acid-ethylene dimethacrylate) monolithic column was simply prepared by in situ co-polymerization of 11 acrylaminoundecanoic acid and ethylene dimethacrylate with 1-propanol, 1,4 butanediol and water as porogens in 100 microm id fused-silica capillary in one step. This column was used in CEC-atmospheric pressure photoionization (APPI)-MS system for separation and detection of N-methylcarbamates pesticides. Numerous parameters are optimized for CEC-APPI-MS. After evaluation of the mobile phase composition, sheath liquid composition and the monolithic capillary outlet position, a fractional factorial design was selected as a screening procedure to identify factors of ionization source parameters, such as sheath liquid flow rate, drying gas flow rate, drying gas temperature, nebulizing gas pressure, vaporizer temperature and capillary voltage, which significantly influence APPI MS sensitivity. A face-centered central composite design was further utilized to optimize the most significant parameters and predict the best sensitivity. Under optimized conditions, S/Ns around 78 were achieved for an injection of 100 ng/mL of each pesticide. Finally, this CEC-APPI-MS method was successfully applied to the analysis of nine N-methylcarbamates in spiked apple juice sample after solid phase extraction with recoveries in the range of 65-109%. PMID- 20349513 TI - Determination of cinchona alkaloids by non-aqueous CE with MS detection. AB - Non-aqueous CZE was investigated for separation of cinchona alkaloids including diastereomeric pairs of analytes such as quinine/quinidine or cinchonine/cinchonidine. BGEs prepared in mixtures of methanol/ethanol/ACN containing formic acid and ammonium formate turned out to provide satisfactory separation selectivity. Resolution was mainly affected by the EOF which could be adjusted by the ratio of the three solvents in the BGE. Contrary to the previous articles, no addition of a chiral selector was necessary. Therefore, the hyphenation with MS was easily possible by means of a sheath-flow-interface. The employment of a Q-TOF MS resulted in mass accuracies typically better than 2 ppm, providing information about the elemental composition of the peaks and allowing identification. Detection limits of CZE-MS were at a level of 0.04 mg/L. The applicability to samples of cinchona bark could be demonstrated, so that this technique can be seen as an attractive alternative to HPLC methods in pharmaceutical quality control. PMID- 20349514 TI - CE-MS and related techniques as a valuable tool in tumor biomarkers research. AB - Cancer has been a disease of great concern because it is the second main cause of death in the world. Cures for most cancer pathologies have not yet been found, and an accurate and early diagnosis is essential for successful treatment. Therefore, research on tumor biomarkers has noticeably increased in recent years. The determination of such biomolecules, together with the routinely used laboratory exams for cancer diagnosis, would constitute a more reliable approach, known as systems biology. The "omics" era has corroborated in such investigations since the development of new technologies has arisen along with it. One of the techniques applied to the investigation of tumor biomarkers is CE, and the increasing applications of CE-MS in this field are also observed. This review covers the published literature on tumor biomarker investigations by CE-MS and related techniques, mostly within the last decade, but not limited to it. For didactic reasons this review is divided into the tumor biomarkers chemical classes, namely, proteins and related molecules, DNA adducts and modified nucleosides. PMID- 20349515 TI - CE-LIF-MS n profiling of oligosaccharides in human milk and feces of breast-fed babies. AB - Mixtures of the complex human milk oligosaccharides (HMOs) are difficult to analyze and gastrointestinal bioconversion products of HMOs may complicate analysis even more. Their analysis, therefore, requires the combination of a sensitive and high-resolution separation technique with a mass identification tool. This study introduces for the first time the hyphenation of CE with an electrospray mass spectrometer, capable to perform multiple MS analysis (ESI MS(n)) for the separation and characterization of HMOs in breast milk and feces of breast-fed babies. LIF was used for on- and off-line detections. From the overall 47 peaks detected in off-line CE-LIF electropherograms, 21 peaks could be unambiguously and 11 peaks could be tentatively assigned. The detailed structural characterization of a novel lacto-N-neo-tetraose isomer and a novel lacto-N fucopentaose isomer was established in baby feces and pointed to gastrointestinal hydrolysis of higher-Mw HMOs. CE-LIF-ESI-MS(n) presents, therefore, a useful tool which contributes to an advanced understanding on the fate of individual HMOs during their gastrointestinal passage. PMID- 20349516 TI - The selective determination of sulfates, sulfonates and phosphates in urine by CE MS. AB - Metabolite identification and metabolite profiling are of major importance in the pharmaceutical and clinical context. However, highly polar and ionic substances are rarely included as analytical tools are missing. In this study, we present a new method for the determination of urinary sulfates, sulfonates, phosphates and other anions of strong acids. The method comprises a CE separation using an acidic BGE (pH0.05). As expected, for a 20-min general ischemia, infarct size in heart slices determined by 2,3,5-triphenyltetrazolium chloride staining among the groups was not obvious. Sevoflurane postconditioning reduces reperfusion arrhythmias without affecting the severity of myocardial stunning. In contrast, sevoflurane preconditioning has no beneficial effects on reperfusion arrhythmias, but it is in favor of improving ventricular function and recovering myocardial stunning. Sevoflurane preconditioning and postconditioning may be useful for correcting the stunned myocardium. PMID- 20349524 TI - Spatial and seasonal characterization of net primary productivity and climate variables in southeastern China using MODIS data. AB - We developed a sophisticated method to depict the spatial and seasonal characterization of net primary productivity (NPP) and climate variables. The role of climate variability in the seasonal variation of NPP exerts delayed and continuous effects. This study expands on this by mapping the seasonal characterization of NPP and climate variables from space using geographic information system (GIS) technology at the pixel level. Our approach was developed in southeastern China using moderate-resolution imaging spectroradiometer (MODIS) data. The results showed that air temperature, precipitation and sunshine percentage contributed significantly to seasonal variation of NPP. In the northern portion of the study area, a significant positive 32-d lagged correlation was observed between seasonal variation of NPP and climate (P<0.01), and the influences of changing climate on NPP lasted for 48 d or 64 d. In central southeastern China, NPP showed 16-d, 48-d, and 96-d lagged correlation with air temperature, precipitation, and sunshine percentage, respectively (P<0.01); the influences of air temperature and precipitation on NPP lasted for 48 d or 64 d, while sunshine influence on NPP only persisted for 16 d. Due to complex topography and vegetation distribution in the southern part of the study region, the spatial patterns of vegetation-climate relationship became complicated and diversiform, especially for precipitation influences on NPP. In the northern part of the study area, all vegetation NPP had an almost similar response to seasonal variation of air temperature except for broad crops. The impacts of seasonal variation of precipitation and sunshine on broad and cereal crop NPP were slightly different from other vegetation NPP. PMID- 20349525 TI - Accumulation of 1-deoxynojirimycin in silkworm, Bombyx mori L. AB - 1-deoxynojirimycin (1-DNJ) contents in the silkworm, Bombyx mori, at different developmental stages and tissues were investigated by using reverse-phase high performance liquid chromatography. The 1-DNJ contents of silkworm larvae change significantly with their developmental stages. The male larvae showed higher accumulation efficiency of 1-DNJ than the females and also a significant variation was observed among the silkworm strains. The present results show that tissue distribution of 1-DNJ was significantly higher in blood, digestive juice, and alimentary canal, but no 1-DNJ was observed in the silkgland. Moreover, 1-DNJ was not found in silkworms fed with artificial diet that does not contain mulberry leaf powder. This proves that silkworms obtain 1-DNJ from mulberry leaves; they could not synthesize 1-DNJ by themselves. The accumulation and excretion of 1-DNJ change periodically during the larval stage. There was no 1 DNJ in the newly-hatched larvae and 1-DNJ was mainly accumulated during the early and middle stages of every instar, while excreted at later stages of larval development. Further, it is possible to extract 1-DNJ from the larval feces and it is optimal to develop the 1-DNJ related products for diabetic auxiliary therapy. PMID- 20349526 TI - A facile approach to construct hybrid multi-shell calcium phosphate gene particles. AB - The calcium phosphate (CaP) particles have attracted much attention in gene therapy. How to construct stable gene particles was the determining factor. In this study, hybrid multi-shell CaP gene particles were successfully constructed. First, CaP nanoparticles served as a core and were coated with DNA for colloidal stabilization. The xi-potential of DNA-coated CaP nanoparticles was -15 mV. Then polyethylenimine (PEI) was added and adsorbed outside of the DNA layer due to the electrostatic attraction. The xi-potential of hybrid multi-shell CaP particles was slightly positive. With addition of PEI, the hybrid multi-shell particles could condense DNA effectively, which was determined by ethidium bromide (EtBr) exclusion assay. The hybrid particles were spherical and uniform with diameters of about 150 nm at proper conditions. By simple modification of PEI, the hybrid multi-shell CaP gene particles were successfully constructed. They may have great potential in gene therapy. PMID- 20349527 TI - Neural decoding based on probabilistic neural network. AB - Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices, such as robot arms, computer cursors, and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper, two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced, the PNN decoder and the modified PNN (MPNN) decoder. In the experiment, rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity, and pressure was recorded by a pressure sensor synchronously. After training, the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their performances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder, with a CC of 0.8657 and an MSE of 0.2563, outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance, indicating that the MPNN decoder can handle different tasks in BMI system, including the detection of movement states and estimation of continuous kinematic parameters. PMID- 20349529 TI - Notes from a desert island II - we will survive. By Caveman. PMID- 20349528 TI - Novel opportunities for computational biology and sociology in drug discovery. AB - Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development,explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery.These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use.Computation can also be used to model research teams and innovative regions and to estimate the value of academy industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies. PMID- 20349531 TI - [How do you present the efficacy of a treatment to your patient?]. PMID- 20349532 TI - Click chemistry generates privileged CH hydrogen-bonding triazoles: the latest addition to anion supramolecular chemistry. AB - The supramolecular chemistry of anions provides a means to sense and manipulate anions in their many chemical and biological roles. For this purpose, Click chemistry facilitated the synthetic creation of new receptors and thus, an opportunity to aid in the recent re-examination of CH...anion hydrogen bonding. This tutorial review will focus on the privileged C-H hydrogen bond donor of the 1,2,3-triazole ring systems as elucidated from anion-binding studies with macrocyclic triazolophanes and other receptors. Triazolophanes are shape persistent and planar macrocycles that direct four triazole and four phenylene CH groups into a 3.7 A cavity. They display strong (log K(Cl(-)) = 7), size dependent halide binding (Cl(-) > Br(-) >> F(-) >> I(-)) and a rich set of binding equilibria. For instance, the too large iodide (4.4 A) can be sandwiched between two pyridyl-based triazolophanes with extreme positive cooperativity. Computational studies verify the triazole's hydrogen bond strength indicating it approaches the traditional NH donors from pyrrole. These examples, those of transport, sensing (e.g., ion-selective electrodes), templation, and versatile synthesis herald the use of triazoles in anion-receptor chemistry. PMID- 20349534 TI - Electrochemical applications. How click chemistry brought biomimetic models to the next level: electrocatalysis under controlled rate of electron transfer. AB - This tutorial review discusses the immobilization of alkyne-terminated cytochrome c oxidase models on azide-functionalized self-assembled monolayers (SAM) coated gold electrodes that was made possible by click chemistry. The rate of electron delivery from the electrode to the model could be tuned by changing the nature of the SAM. Biologically relevant electron transfer rates (2-4 s(-1)) were obtained on slow SAMs allowing the model to turn over catalytically under steady-state conditions. Hence, click chemistry was a crucial tool to demonstrate, through electrocatalytic studies: (1) the role played by several features present in the distal side of the model, such as the Cu(B)-Tyr244 pair, the distal pocket, and the stabilizing role of a distal water cluster; (2) the reversible inhibition of O(2) reduction by H(2)S. PMID- 20349533 TI - Cu-free click cycloaddition reactions in chemical biology. AB - Bioorthogonal chemical reactions are paving the way for new innovations in biology. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems--in some cases, living organisms. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. PMID- 20349536 TI - Desorption corona beam ionization source for mass spectrometry. AB - A novel Desorption Corona Beam Ionization (DCBI) source for direct analysis of samples from surface in mass spectrometry is reported. The DCBI source can work under ambient conditions without time-consuming sample pretreatments. The source shares some common features with another ionization source - Direct Analysis in Real Time (DART), developed earlier. For example, helium was used as the discharge gas (although only corona discharge is involved in the present source), and heating of the discharge gas is required for sample desorption. However, the difference between the two sources is substantial. In the present source, a visible thin corona beam extending out around 1 cm can be formed by using a hollow needle/ring electrode structure. This feature would greatly facilitate localizing sampling areas and performing imaging/profiling experiments. The DCBI source is also capable of performing progressive temperature scans between room temperature and 450 degrees C in order to sequentially desorb samples from the surface and, therefore, to achieve a rough separation of the individual components in a complex mixture, resulting in less congestion in the mass spectrum acquired. Mass spectra for a broad range of compounds (pesticides, veterinary additives, OTC drugs, explosive materials) have been acquired using the DCBI source. For most of the compounds tested, the heater temperature required for efficient desorption is at least 150 degrees C. The molecular weight of the sample that can be desorbed/ionized is normally below 600 dalton even at the highest heater temperature, which is mainly limited by the volatility of the sample. PMID- 20349535 TI - Fast transient analysis and first-stage collision-induced dissociation with the flowing atmospheric-pressure afterglow ionization source to improve analyte detection and identification. AB - The recent development of ambient desorption/ionization mass spectrometry (ADI MS) has enabled fast, simple analysis of many different sample types. The ADI-MS sources have numerous advantages, including little or no required sample pre treatment, simple mass spectra, and direct analysis of solids and liquids. However, problems of competitive ionization and limited fragmentation require sample-constituent separation, high mass accuracy, and/or tandem mass spectrometry (MS/MS) to detect, identify, and quantify unknown analytes. To maintain the inherent high throughput of ADI-MS, it is essential for the ion source/mass analyzer combination to measure fast transient signals and provide structural information. In the current study, the flowing atmospheric-pressure afterglow (FAPA) ionization source is coupled with a time-of-flight mass spectrometer (TOF-MS) to analyze fast transient signals (<500 ms FWHM). It was found that gas chromatography (GC) coupled with the FAPA source resulted in a reproducible (<5% RSD) and sensitive (detection limits of <6 fmol for a mixture of herbicides) system with analysis times of ca. 5 min. Introducing analytes to the FAPA in a transient was also shown to significantly reduce matrix effects caused by competitive ionization by minimizing the number and amount of constituents introduced into the ionization source. Additionally, MS/MS with FAPA TOF-MS, enabling analyte identification, was performed via first-stage collision induced dissociation (CID). Lastly, molecular and structural information was obtained across a fast transient peak by modulating the conditions that caused the first-stage CID. PMID- 20349537 TI - Direct analysis of dried blood spots utilizing desorption electrospray ionization (DESI) mass spectrometry. AB - A novel approach to the quantitative determination of xenobiotics in whole blood samples without sample preparation or chromatography is described. This method is based on direct analysis of microlitre volumes of blood which are spotted onto specialized paper cards and dried, with the resulting dried blood spots (DBS) analyzed directly via desorption electrospray ionization (DESI) mass spectrometry (MS). Using sitamaquine, terfenadine, and prazosin as model compounds with verapamil as a common internal standard, this methodology demonstrated detection of each compound down to 10 ng mL(-1) from DBS where standard calibration curves show linearity from 10-10,000 ng mL(-1) with r(2) > 0.99. Three (3) different untreated types of filter papers (Whatman 903 and 31ETF as well as Ahlstrom 237) and two (2) treated types of filter paper (Whatman FTA and FTA Elute) were examined and the effect of each surface on the recovery of each analyte was evaluated. The results show that the untreated papers provide the best substrates for DBS analysis by DESI. A more in depth study of the quantitation of sitamaquine on 31ETF paper stock provided bias and error measurements of less than 20%. The promising results shown in this study may have important implications in the areas of therapeutic drug monitoring (TDM), clinical and forensic toxicology, and pharmacology. PMID- 20349538 TI - The effect of electrospray solvent composition on desorption electrospray ionisation (DESI) efficiency and spatial resolution. AB - In desorption electrospray ionisation (DESI) the interaction between the electrospray and the surface is key to two important analytical parameters, the spatial resolution and the sensitivity. We evaluate the effect of the electrospray solvent type, organic solvent fraction with water, analyte solubility and substrate wettability on DESI erosion diameter and material transferral into useful ion signal. To do this five amino acids, glycine, alanine, valine, leucine and phenylalanine are prepared as thin films on three substrates, UV/ozone treated glass, glass and polytetrafluoroethylene (PTFE). Four different solvents, acetonitrile (ACN), methanol (MeOH), ethanol (EtOH) and propan-2-ol (IPA), are used with organic solvent fractions with water varying from 0.1 to 1. These model systems allow the solubility or wettability to be kept constant as other parameters are varied. Additionally, comparison with electrospray ionisation (ESI) allows effects of ionisation efficiency to be determined. It is shown that the DESI efficiency is linearly dependent on the solubility (for these materials at least) and for analytes with solubilities below 1.5 g kg(-1), additional strategies may be required for DESI to be effective. We show that the DESI erosion diameter improves linearly with organic solvent fraction, with an organic solvent fraction of 0.9 instead of 0.5 leading to a 2 fold improvement. Furthermore, this leads to a 35 fold increase in DESI efficiency, defined as the molecular ion yield per unit area. It is shown that these improvements correlate with smaller droplet sizes rather than surface wetting or ionisation. PMID- 20349539 TI - Instantaneous characterization of vegetable oils via TAG and FFA profiles by easy ambient sonic-spray ionization mass spectrometry. AB - A fast and reliable method is presented for the analysis of vegetable oils. Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) is shown to efficiently desorb and ionize the main oil constituents from an inert surface under ambient conditions and to provide comprehensive triacylglyceride (TAG) and free fatty acid (FFA) profiles detected mainly as either [TAG + Na](+) or [FFA H](-) ions. EASI(+/-)-MS analysis is simple, easily implemented, requires just a tiny droplet of the oil and is performed without any pre-separation or chemical manipulation. It also causes no fragmentation of TAG ions hence diacylglyceride (DAG) and monoacylglyceride (MAG) profiles and contents can also be measured. The EASI(+/-)-MS profiles of TAG and FFA permit authentication and quality control and can be used, for instance, to access levels of adulteration, acidity, oxidation or hydrolysis of vegetable oils in general. PMID- 20349540 TI - Direct analysis of lipids and small metabolites in mouse brain tissue by AP IR MALDI and reactive LAESI mass spectrometry. AB - Ambient analysis of metabolites and lipids from unprocessed animal tissue by mass spectrometry remains a challenge. The utility of the two novel ambient ionization techniques--atmospheric pressure infrared matrix-assisted laser desorption ionization (AP IR-MALDI) and laser ablation electrospray ionization (LAESI)--is demonstrated for the direct mass spectrometric analysis of lipids and other metabolites from mouse brain. Major brain lipids including cholesterol, various phospholipid species (glycerophosphocholines, sphingomyelin and phosphatidylethanolamines) along with numerous metabolites, for example g aminobutyric acid (GABA), creatine and choline, were identified in a typical mass spectrum. In a new ionization modality of LAESI, termed reactive LAESI, in-plume reactions with a solute of choice (lithium sulfate) enhanced structure-specific fragmentation of lipid ions for improved molecular assignment in collision activated dissociation experiments. In-plume processes in reactive LAESI provide additional structural information without contaminating the biological sample with the reactant. PMID- 20349542 TI - Geometry-independent neutral desorption device for the sensitive EESI-MS detection of explosives on various surfaces. AB - A novel geometry-independent neutral desorption (GIND) device was successfully developed, which made neutral desorption (ND) sampling easier and more robust on virtually all types of surfaces. The GIND device features a small air-tight enclosure with fixed space between the ND gas emitter, the sample surface, and the sample collector. Besides easy fabrication and convenient use, this configuration facilitates efficient neutral sample transfer and results in high sensitivity by preventing material loss during the ND process. The effects of various operating parameters of the GIND device such as desorption gas composition, surface wetness, gas flow rate, distance between the surface and the gas emitter, internal diameter of the sample outlet, and GIND device material were experimentally investigated. By using the GIND device, trace amounts of typical explosives such as TNT, RDX, HMX, TATP, etc., were successfully sampled from many different kinds of surfaces, including human skin, glove, glass, envelope, plastic, leather, glass, and clothes. GIND-sampled explosives were detected by multiple-stage extractive electrospray ionization mass spectrometry (EESI-MS). Ion/molecule reactions of explosives such as RDX and TATP were implemented in the EESI source for the rapid detection with enhanced sensitivity and specificity. The typical time for a single sample analysis was a few seconds. Successful transportation of the neutral analytes over a distance longer than 10 m was demonstrated, without either significant signal loss or serious delay of signal response. The limit of detection for these explosives in the study was in the range of ca. 59-842 fg (S/N = 3, n = 8) on various surfaces. Acceptable relative standard deviation (RSD) values (ca. 4.6-10.2%, n = 8) were obtained for all the surfaces tested, showing the successful sampling of trace non-volatile explosive compounds (sub-picogram) by the GIND device for the EESI mass spectrometric analysis. PMID- 20349543 TI - Direct analysis of sterols from dried plasma/blood spots by an atmospheric pressure thermal desorption chemical ionization mass spectrometry (APTDCI-MS) method for a rapid screening of Smith-Lemli-Opitz syndrome. AB - Here is proposed a rapid and sensitive method involving atmospheric pressure thermal desorption chemical ionization mass spectrometry (APTDCI-MS) for specific laboratory screening of the Smith-Lemli-Opitz syndrome (SLOS), an inherited defect of cholesterol biosynthesis. Biochemical findings in the blood of SLOS patients are low cholesterol (Chol), high 7- and 8-dehydrocholesterol (DHCs) levels and high DHCs/Chol ratios. The APTDCI proposed method is able to ionize sterols for qualitative and quantitative analysis directly from dried plasma/blood spots. Critical APTDCI parameters--desolvation gas flow and temperature--were optimized analyzing Chol, 7-DHC and cholesteryl stearate standards spotted onto a glass slide acquiring the full scan spectra in positive ion mode. Chol levels in dried plasma spots of unaffected controls (n = 23) obtained by the proposed method were compared with those of the enzymatic method (y = 0.9166x + 0.3811; r = 0.8831) while Chol and DHCs of SLOS patients (n = 9) were compared with the gas chromatography flame ionization detection (GC-FID) method (y = 0.8214x + 0.7388; r = 0.8288). The APTDCI-MS method is also able to differentiate normal from SLOS samples directly analyzing whole blood and washed red cells spotted on paper. In conclusion, the intrinsic analytical high throughput of APTDCI-MS method for sterol analysis could be useful to screen SLO syndrome. PMID- 20349541 TI - Electrospray-assisted laser desorption ionization mass spectrometry (ELDI-MS) with an infrared laser for characterizing peptides and proteins. AB - An electrospray-assisted laser desorption/ionization source with an infrared OPO laser (IR-ELDI) was constructed and optimized for peptide and protein mass spectrometry analysis. Similar to ELDI with an ultraviolet laser, IR-ELDI generates multiply charged molecules for peptides and proteins measured under ambient sampling conditions. Both samples in the dried state and analyte solutions can be directly measured by IR-ELDI without the presence of a conventional MALDI matrix. However, the analysis of sample solutions is shown to greatly enhance the sensitivity of the mass spectrometry measurement, as a 100 fold sensitivity gain for peptide measurements was measured. The limit of detection of IR-ELDI was determined to be 250 fmol for bradykinin (1.1 kDa), 100 fmol for ubiquitin (8.6 kDa), and 500 fmol for carbonic anhydrase (29 kDa). IR ELDI is amenable for MS and MSn analysis for proteins up to 80 kDa transferrin. IR-ELDI-MS may be a useful tool for protein sequencing analysis from complex biological matrices, with minimal sample preparation required. PMID- 20349544 TI - American Academy of Pediatric Dentistry reference manual 2005-2006. PMID- 20349545 TI - American Academy of Pediatric Dentistry reference manual 2008-2009. PMID- 20349546 TI - Cholera vaccines: WHO position paper. PMID- 20349547 TI - Meeting of the International Task Force for Disease Eradication, January 2010 - Tuberculosis: review and recommendations. PMID- 20349548 TI - Vocational Rehabilitation and Employment Program--periods of eligibility. Final rule. AB - This document adopts without change the proposed rule published in the Federal Register on March 9, 2009, amending regulations of the Department of Veterans Affairs (VA) concerning periods of eligibility applicable to VA's provision of Vocational Rehabilitation and Employment benefits and services. The amendments clarify program requirements, interpret and incorporate new statutory requirements, and make clarifying non-substantive changes. PMID- 20349549 TI - Vocational Rehabilitation and Employment program--self-employment. Final rule. AB - This document amends the vocational rehabilitation and employment regulations of the Department of Veterans Affairs (VA) concerning self-employment for individuals with qualifying disabilities. We are making changes to conform VA's regulations for self-employment programs for veterans, and for servicemembers awaiting discharge, to statutory provisions, including provisions limiting eligibility for certain supplies, equipment, stock, and license fees to individuals with the most severe service-connected disabilities. We are also making related changes in VA's regulations affecting eligibility for such assistance for certain veterans' children with birth defects in self-employment programs. In addition, we are amending our regulations regarding the approval authority for self-employment plans to make certain requirements less restrictive and less burdensome, to remove a vague and overly broad requirement, to make changes to reflect longstanding VA policy, and to make nonsubstantive clarifying changes. PMID- 20349550 TI - [Images of female slaves in Rio de Janeiro daily life, 1808-22]. PMID- 20349551 TI - Computational intelligence community. Introduction. PMID- 20349552 TI - International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice. AB - The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources. PMID- 20349553 TI - Byzantine medical manuscripts: towards a new catalogue, with a specimen for an annotated checklist of manuscripts based on an index of Diels' Catalogue. AB - Greek manuscripts containing medical texts were inventoried at the beginning of the 20th century by a team of philologists under the direction of Hermann Diels. The resulting catalogue, however useful it was when new and still is today, needs to be updated not only because some manuscripts have been destroyed, certain collections and single items have changed location, new shelfmark systems have been sometimes adopted and cataloguing has made substantial progress, but also because in Diels' time the concept of ancient medicine was limited, the method used in compiling data was not standardized and, in a time of manual recording and handling of information, mistakes could not be avoided. The present article is an introduction to a new catalogue of Greek medical manuscripts. In the first part, it surveys the history of the heuristic and cataloguing of Greek medical manuscripts from the 16th century forward; in the second part, it highlights the problems in Diels' catalogue and describes the genesis and methods of the new catalogue, together with the plan for its completion; and in the third part, it provides a sample of such a new catalogue, with a list of the Greek medical manuscripts in the libraries of the United Kingdom and Ireland. PMID- 20349554 TI - Phase relation changes between the firings of alpha and gamma-motoneurons and muscle spindle afferents in the sacral micturition centre during continence functions in brain-dead human and patients with spinal cord injury. AB - 1. Single-nerve fibre action potentials (APs) were recorded with 2 pairs of wire electrodes from lower sacral nerve roots during surgery in patients with spinal cord injury and in a brain-dead human. Conduction velocity distribution histograms were constructed for afferent and efferent fibres, nerve fibre groups were identified and simultaneous impulse patterns of alpha and gamma-motoneurons and secondary muscle spindle afferents (SP2) were constructed. Temporal relations between afferent and efferent APs were analyzed by interspike interval (II) and phase relation changes to explore the coordinated self-organization of somatic and parasympathetic neuronal networks in the sacral micturition centre during continence functions under physiologic (brain-dead) and pathophysiologic conditions (spinal cord injury). 2. In a paraplegic with hyperreflexia of the bladder, urinary bladder stretch (S1) and tension receptor afferents (ST) fired already when the bladder was empty, and showed a several times higher bladder afferent activity increase upon retrograde bladder filling than observed in the brain-dead individual. Two alpha2-motoneurons (FR) innervating the external bladder sphincter were already oscillatory firing to generate high activity levels when the bladder was empty. They showed activity levels with no bladder filling, comparable to those measured at a bladder filling of 600 ml in the brain dead individual. A bladder storage volume of 600 ml was thus lost in the paraplegic, due to a too high bladder afferent input to the sacral micturition center, secondary to inflammation and hypertrophy of the detrusor. 3. In a brain dead human, 2 phase relations existed per oscillation period of 160 ms between the APs of a sphincteric oscillatory firing alpha2-motoneuron, a dynamic fusimotor and a secondary muscle spindle afferent fibre. Following stimulation of mainly somatic afferent fibres, the phase relations changed only little. 4. In a paraplegic with dyssynergia of the urinary bladder also 2 phase relations (less stable) existed per oscillation period of 110 ms in a functional unit between the APs of a sphincteric alpha-motoneuron, a fusimotor and a secondary spindle afferent fibre. The phase relations changed with time following stimulation of mainly somatic afferents. A second functional unit organized by phase related interactions was phase related to the first functional unit. 5. Following painful bladder catheter pulling, the parasympathetic division was transiently activated several times in the paraplegic. At times of activation of the parasympathetic division, 3 broad phase relations occurred within and between the two functional units, indicating that the parasympathetic division in the sacral micturition and defecation center channeled an additional input to the somatic oscillatory firing neuronal networks driving motoneurons which innervate the external bladder and/or anal sphincters. 6. It is conceivable that the mutual inhibitory action of detrusor and external bladder sphincter has the capacity to recover, if the functional neuronal organization of the sacral micturition center is improved in the direction of more stable phase relations between the firings of neurons and neuronal ensembles by natural coordinated afferent inputs from continence organs, supraspinal neurons, and functionally connected neuronal networks. For supraspinal control and improvement of neuronal organization some kinds of bulbo spinal-bulbo pathways have to exist or to be reconstructed by regeneration. 7. It will be shown in a following article that the sacral micturition centre can be repaired after spinal cord injury by a functional reorganization and limited regeneration of the human spinal cord by administering coordination dynamics therapy. PMID- 20349555 TI - Sympathetic skin response (SSR) in Crohn disease: a pilot study. AB - Peripheral neuropathy is one of the most frequently reported neurological extra intestinal manifestations of the Crohn disease. Former studies have showed sympathetic neuropathy as early manifestation of CD by physical tests. The aim of this study is to examine sympathetic neuropathy in CD by using sympathetic skin response (SSR). We performed SSR on 6 Patients (4 male, 2 female) that were diagnosed as CD. Their age was between 26 till 68 years with the mean of (43.3 +/ 17.1) years. The duration of their disease was at least 4 years (mean: 9.0 +/- 8.4) and none of the patients had any symptoms or signs related to autonomic nervous system dysfunction. Hand and foot latencies in CD patients were prolonged relative to controls and the difference of hand latencies was statistically significant. Two patients demonstrated total abnormal results. In conclusion, there is some sub-clinical sympathetic dysfunction in CD patient. This suggests that SSR can be useful in detecting early autonomic changes in these patients. PMID- 20349556 TI - Electromyographic evaluation during masticatory function, in patients with temporomandibular disorders following interocclusal appliance treatment. AB - The aim of this study was to evaluate the electromyographic activity during masticatory function, in patients with stomatognathic system dysfunctions, treated with interocclusal splints. Electromyography was carried out through a computer diagnostic system K6-l DIAGNOSTIC SYSTEM (Myo-Tronics, Inc.; Tukwila, WA; USA). Study sample involved 20 individuals, age 18-53 years, both genders. Electromyographic activity of the masticatory muscles (masseter and anterior temporalis) was measured before and 90, 120, and 150 days after treatment with interocclusal splints, which were modified at days 90 (in canine guidance) and 120 (in group function). Data were statistically analyzed through a simple linear regression model. There was no statistically significant difference (p > 0.05) among the 3 periods assessed. Bilateral equilibrium of electromyographic activity was observed for the masseter and anterior temporalis muscles during the treatment. PMID- 20349557 TI - Leg muscles activities during hyperventilation following a cycling exercise. AB - The goal of this study was to establish how increased ventilation modifies postural stability, as characterized by body sway and leg muscle activities. Twelve healthy subjects had to perform six 30-second postural tests: one pre exercise test while breathing gently and then one test every minute for the five minutes immediately following a maximum-intensity, incremental cycling exercise test. Subjects were asked to maintain an upright stance on a force plate for 30 s, with their eyes open. Movement of the centre of pressure in the sagittal plane was monitored in the time and spectral domains. Myoelectric activities of the soleus and tibialis anterior muscles were recorded using surface electromyography. Ventilatory parameters were measured with a portable, telemetric device. Postural changes related to respiratory variations were quantified by coherence analysis. The results showed that hyperventilation induced by exercise was accompanied by a significant increase in postural parameters, indicating a reduction in postural stability following a change in ventilatory drive. Coherence analysis confirmed the ventilatory origin of the postural oscillations. The results suggest that ventilation may be an important factor in postural disturbance during physical activity. The observed increases in leg muscle activities were most likely related to musculo-articular stiffening. PMID- 20349558 TI - Neurophysiological comparison between the Sit-to-Stand test with the 6-Minute Walk test in individuals with COPD. AB - OBJECTIVES: The Sit-to-Stand test (SST) is accepted and utilized during functional assessments of COPD patients, along with the 6-Minute Walk test (6MWT). Since there is a lack of evidence in literature regarding the neurophysiological effectiveness of SST compared to 6MWT, the present study is justified with the purpose of assessing the neurophysiological effectiveness of SST in comparison to the 6MWT during the functional assessment of such patients, once it is known that both tests are good predictors of functional state. METHODS: Fourteen patients with moderate to severe COPD randomly performed the 6MWT and the SST with a 30-minute interval in between tests. Blood lactate was collected along with the median frequency (MDF), obtained with the electromyography of the muscles rectusfemoris (RF), vastus lateralis (VL), tibialis anterior (TA), and soleus (SO) for the comparison of the neurophysiological effectiveness. RESULTS: The results of the blood lactate concentration during rest and at the end of the functional tasks along with the results from the angular coefficient (AC) obtained from the median frequency were analyzed with the Student t test. The initial and final values obtained from SST and 6MWT were compared within each activity, along with the comparison between the initial and final values for each functional test. A significant difference (p = 0.0005) was only verified between the initial and final values of SST. CONCLUSION: We found neurophysiological correlation between both tests which enabled us to suggest that SST may determine functional status as easily as the 6MWT in regard to neurophysiological effectiveness. PMID- 20349559 TI - Electromyographic analysis of biceps brachii muscle following neural mobilization in patients with stroke. AB - OBJECTIVES: The proposal of the present study is based on mobilizing the nervous system of the upper hemiplegic limb of stroke victims using the Upper Limb Neurodynamic Test (ULNT 1) and electromyographic analysis of the biceps brachii muscle. METHODS: A pre-experimental study was carried out with pretest and posttest repeated measurements on five stroke victims (4 men and 1 woman; mean age: 52.8 +/- 11 years), with Grade 1 and + 1 spasticity, according to the modified Ashworth scale. Electromyographic analysis of the biceps brachii muscle was performed with the elbow flexed at 90 degrees, following by complete extension. RESULTS: The neurodynamic test led to a decrease in electromyographic activity in the biceps brachii muscle (p < or = 0.05). CONCLUSION: Neural mobilization was efficient in reducing myoelectric activity in the biceps brachii muscle in patients with stroke and may used by physiotherapists as an efficient method for treating patients with this pathology. PMID- 20349560 TI - A complementary approach for evaluating S1-root in diabetic neuropathic patients. AB - Diabetic neuropathy is one of the most common causes of peripheral neuropathy. Conventional electrodiagnostic evaluation or even magnetic resonance imaging (MRI) of lumbosacral vertebrae cannot confirm radiculopathy (e.g S1-root irritation) in diabetic neuropathic patients definitely. The purpose of the present study was to evaluate spinal nerve pathway of H-reflex in diabetic neuropathic patients by the central loop of H-reflex when its conventional pathway was impaired. No similar study, however, has been done on this subject. Forty two diabetic neuropathic patients with impaired conventional H-reflex were studied by the central loop of H-reflex bilaterally. The central loop of H-reflex was elicited by monopolar needle stimulation of S1 nerve root at the level of S1 foramen and recorded in the half way of the line from popliteal crease to the medial malleolus. In 82 out of 84 (97.6%) limbs with impaired conventional H reflex, the central loop of H-reflex was measurable with latency less than 8 ms. Therefore the central loop of H-reflex was a more reliable approach for investigating S1-root in these patients with significant statistical difference (P < 0.001). The central loop of H-reflex latency in this study was 6.34 +/- 0.96 ms with the range of 4.3-7.85 ms. In conclusion the presence of central loop of H reflex with latency less than 8 ms can be used as a complementary approach for assessment of S1-root sparing in diabetics. PMID- 20349562 TI - Problem solved, LOL. PMID- 20349561 TI - Internet ideology war. PMID- 20349563 TI - Swept away. PMID- 20349564 TI - Biofuel from bacteria. PMID- 20349565 TI - Higher watermarks. PMID- 20349566 TI - Static over statins. PMID- 20349567 TI - Making scents of sounds. PMID- 20349568 TI - Chemical controls. PMID- 20349569 TI - Expert systems fight poverty. PMID- 20349570 TI - The sensed-presence effect. PMID- 20349571 TI - Dark matters. PMID- 20349572 TI - Eight Wonders of the solar system. AB - Artist Ron Miller takes us on a journey to eight of the most breathtaking views that await intrepid explorers of our solar system. The scale of these natural wonders dwarfs anything Earth has to offer. What might we see and feel if we could travel to these distant domains? The artist's eye-interpreting data from probes such as NASA's Cassini, which is now exploring the Saturnian system, and MESSENGER, which has flown by Mercury three times and goes into permanent orbit next March-allows us an early visit to these unforgettable locales. PMID- 20349573 TI - Faulty circuits. PMID- 20349574 TI - Boundaries for a healthy planet. PMID- 20349575 TI - Solutions to environmental threats. PMID- 20349576 TI - Breaking the growth habit. PMID- 20349577 TI - Bill McKibben Challenged: is zero growth really necessary? Interview by Mark Fischetti. PMID- 20349578 TI - Regaining balance with bionic ears. PMID- 20349579 TI - The rise of instant wireless networks. PMID- 20349580 TI - The hidden life of truffles. PMID- 20349581 TI - We've entered the fourth decade in the battle against HIV/AIDS. PMID- 20349582 TI - On the scientific trail in Santa Fe. PMID- 20349583 TI - Antibodies: beyond neutralization. PMID- 20349584 TI - Prevent and conquer. PMID- 20349585 TI - Adding to the armamentarium of broadly neutralizing antibodies. PMID- 20349586 TI - Fatal outcome of spontaneous cerebral and intraventricular hemorrhage in a child with idiopathic thrombocytopenic purpura (ITP)--case report. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is the most prevalent acquired hemorrhagic diathesis in children characterised by antibody-mediated destruction of platelets. ITP is generally a self-limiting benign disorder but despite this good prognosis, ITP carries the risk of severe bleeding (mainly intracranial) that may threaten the child's life. CASE REPORT: We describe a case of a 5-year-old girl with idiopathic thrombocytopenic purpura in the course of EBV infection with massive cerebral and intraventricular hemorrhage and fatal outcome. CONCLUSION: This extremely rare case of intracranial haemorrhage in a child with ITP coexisting with EBV infection (a likely additional risk factor for hemorrhage) deserves attention considering the fatal outcome despite intensive treatment. PMID- 20349587 TI - [Intralesional corticosteroid therapy in infantile hemangiomas]. AB - INTRODUCTION: This study was undertaken to evaluate the effectiveness of intralesional corticosteroid therapy in infantile hemangiomas. MATERIAL AND METHODS: The study was done in 38 patients aged 1 month to 14 years with infants accounting for 84% of all patients. Physical investigation was carried out before and after treatment. Localization, size of tumor, pressure, and surface features were recorded. Doppler ultrasound was performed concomitantly and served to measure tumor size and blood flow in tumor vasculature. Midazolanium 1-2 mg/kg was administered intravenously without general anesthesia. Treatment consisted of 3-5 doses of Polcortolon with intervals of 5-6 weeks between doses. The corticosteroid dose was individualized and depended on tumor size and age of patient. The results were analyzed with the modified Sloan's scale. RESULTS: Hemangioma was disclosed immediately after birth in 30 patients (78%). The tumor had an intense cherry color and demonstrated increased pressure and fast enlargement during the first weeks of life. In the remaining eight patients (22%), the tumor appeared after the second month of life and failed to show features of fast growth during the first year of life. The location of hemangioma was on the head and neck in 22 children (58%) and on the chest, extremities, abdomen, or lower back (lumbar region) in the remaining children. Doppler ultrasound revealed increased vascular flow in the tumor of all patients. Intralesional corticosteroid therapy resulted in reduction of tumor volume of more than 50% in 18 (47%), less than 50% in 12 (32%), and little or no change in eight (21%) cases. A very good result in one patient was achieved with two weeks of supplemental oral Prednisolon therapy. Total or partial excision of the tumor for aesthetic reasons was done in eight patients in whom intralesional corticosteroid therapy produced substantial reduction in tumor size. CONCLUSIONS: Intralesional corticosteroid therapy is an effective and safe modality particularly suitable for the management of extensive hemangiomas of the head and neck when surgical options are limited. PMID- 20349588 TI - [Proliferation index and its prognostic value in invasive ductal breast carcinoma]. AB - BACKGROUND: Decisions in breast cancer as to treatment options supplementing surgery are based on classic prognostic factors. However, these factors are of little help when deciding against adjuvant chemo-/hormonotherapy. Therefore, there is a need to search for additional factors which modify the prognosis in breast cancer patients. The aim of this study was to determine associations of the proliferation index (PI) with some clinical and anatomical factors, as well as with the overall survival (OS) and distant metastasis-free survival (DMS) rates in invasive ductal breast cancer. The study also attempted to identify independent prognostic factors. MATERIAL AND METHODS: PI was calculated following immunohistochemistry with a monoclonal antibody against Ki-67 (MIB-1) protein in 767 invasive ductal breast cancer patients seen at the West Pomeranian Oncology Center between 1990 and 2001. The mean follow-up time in the group of surviving patients was 72.7 months. The cut-off value of 10% for high/low PI was adopted. RESULTS: The mean value of PI was 15.15% (median 11.2%). High PI correlated with young age of patient, tumor diameter, high histological malignancy score, absence of estrogen receptor in cells, and metastases to axillary lymph nodes. The frequency of distant metastases and high mortality risk correlated with high PI in the whole group and in subgroups without or with metastases to 1-3 axillary lymph nodes, with grade II cancers according to the B-R score, and with the presence of estrogen receptors in the tumor. PI proved to be an independent prognostic factor in the whole group and in the subgroup of patients with axillary node metastases. PI was the sole independent prognostic factor in patients with metastases to 1-3 axillary lymph nodes. CONCLUSIONS: PI is an independent prognostic factor in patients with invasive ductal breast carcinoma. PI can be used to identify patients with a worse prognosis among patients with metastases to 1-3 axillary lymph nodes or with grade II cancer according to the Bloom-Richardson score. PI strongly correlates with other pathological and clinical parameters. In combination with other prognostic factors, PI can be used for prediction of metastases to axillary lymph nodes. PMID- 20349589 TI - [Thermographic examination of cutaneous melanocytic nevi]. AB - STUDY OBJECTIVES: Comparative examination with dermoscopy, thermography, and histopathology of cutaneous melanocytic nevi. MATERIAL AND METHODS: The study was done in 245 patients with 735 melanocytic nevi and in 12 patients with malignant melanoma. All melanocytic lesions were studied with Heine delta 10 dermatoscope and the total dermatoscopy score (TDS) was calculated. ThermaCAM S.C.500 thermographic camera was used to measure the maximal (Tmax), minimal (Tmin), and average temperatures and to calculate the difference between maximal and minimal temperatures deltaT (degrees C) = Tmax - Tmin for all lesions. Histopathology was performed in the case of 127 melanocytic nevi and 12 malignant melanomas. Statistical analysis was done using Statistica 6.0 software. Mean values in the groups were compared with Student's t-test and Pearson's linear correlation coefficient (r) was calculated to disclose relationships between variables. RESULTS: TDS was 4.03 +/- 0.68 for all 735 melanocytic nevi, 3.89 +/- 0.30 for 554 ordinary melanocytic nevi, 5.19 +/- 0.21 for 181 atypical melanocytic nevi, and 5.96 +/- 0.25 for 12 malignant melanomas. Mean maximal temperature for all 735 melanocytic nevi was 33.5 +/- 0.3 degrees C and did not differ significantly from the control group (33.2 +/- 0.6 degrees C; p > 0.05). Mean maximal temperature was 33.1 +/- 0.7 degrees C (p > 0.05) for 554 benign melanocytic nevi, 33.7 +/- 0.4 degrees C (p < 0.05) for 181 atypical melanocytic nevi, and 34.1 degrees 0.8 degrees C (p < 0.01) for 12 malignant melanomas. Mean average temperature for all 735 melanocytic nevi was 31.9 +/- 1.0 degrees C and did not differ significantly from the control group (31.8 +/- 0.9 dgrees C; p > 0.05). Mean average temperature was 31.8 +/- 1.0 degrees C (p > 0.05) for 554 benign melanocytic nevi, 32.0 +/- 1.1 degrees C (p > 0.05) for 181 atypical melanocytic nevi, and 33.0 +/- 0.9 degrees C (p < 0.01) for 12 malignant melanomas. Mean deltaT (degrees C) for all melanocytic nevi was 1.2 +/- 0.2 and did not differ significantly from the control group (1.1 +/- 0.2; p > 0.05). Mean deltaT (degrees C) was 1.1 +/- 0.3 (p > 0.05) for 554 benign melanocytic nevi, 1.39 +/- 0.28 (p < 0.001) for 181 atypical melanocytic nevi, and 1.6 +/- 0.4 (p < 0.001) for 12 malignant melanomas. Positive correlations were found between the results of dermoscopic, thermographic, and histopathologic examination of melanocytic nevi. CONCLUSIONS: (1) Thermography may supplement dermoscopy during examination of atypical melanocytic nevi and other skin lesions suspected of neoplastic metaplasia. (2) Dermoscopic findings (including TDS) correlate with thermographic findings--including deltaT (degrees C), as well as with histopathologic findings. (3) Melanocytic nevi demonstrating delta (degrees C) > 1.4 and TDS > 4.75 require surgical intervention or follow-up for neoplastic metaplasia. (4) Average temperatures of benign and atypical melanocytic nevi do not differ significantly from the average temperature of the skin without pigmented lesions. PMID- 20349590 TI - [Comparison of two surgical methods as to early results in chronic subdural hematoma]. AB - OBJECTIVE: Despite general agreement among neurosurgeons concerning operative treatment in chronic subdural hematoma (CSDH), the optimal procedure remains controversial. Two surgical approaches are available: evacuation of hematoma fluid by trepanation; craniotomy and removal of hematoma with surrounding membranes. The main goal of this study was to compare the results of treatment in CSDH depending on the method of surgery. MATERIAL AND METHODS: This retrospective study was done basing on case histories and computed tomography findings in 433 patients with CSDH operated between 1983 and 2003 at the Department ofNeurotraumatology, Jagiellonian University. Altogether, 495 neurosurgical procedures were done. Hematoma was managed by burr hole evacuation in 333 cases and by craniotomy in 162 cases. RESULT: Neurological grading on discharge indicated that trepanation produced significantly better results than craniotomy. CONCLUSIONS: (1) In comparison with literature data and by separate evaluation, the results of treatment in CSDH at the Department of Neurotraumatology were good in trepanation and craniotomy groups alike. (2) Literature data and case histories of the present study demonstrate that burr hole evacuation is the preferred method of treatment in CSDH. (3) In the overwhelming majority of cases, computed tomography fails to identify CSDH patients necessitating craniotomy. PMID- 20349591 TI - [Measurement of anxiety with C.D. Spielberger's test in patients with cardiac arrhythmias]. AB - INTRODUCTION: Atrial fibrillation is a common supraventrical arrhythmia. The onset of fibrillation is marked by fear of loss of health or life. Symptoms of depression occur concurrently. This study was undertaken to measure anxiety in patients with atrial fibrillation grouped according to gender, age, and education. MATERIAL AND METHODS: The test anxiety inventory of C.D. Spielberger was administered to 52 patients aged 41 to 80 years, treated for atrial fibrillation at the Internal Ward of the District Hospital in Bialogard. RESULTS: Anxiety as a state was observed more frequently in males and in patients with vocational and secondary education. Anxiety was not a trait of atrial fibrillation. Psychotherapeutic interventions used in cardiac rehabilitation are not recommended in atrial fibrillation. However, relaxation techniques could be of benefit in reducing the intensity of anxiety as a state. PMID- 20349592 TI - [Surgery with neuronavigated mapping of cerebral cavernoma evoking epileptic seizures]. AB - INTRODUCTION: Cavernous hemangioma is increasingly recognized as the cause of epilepsy attributed to vasogenic foci. The clinical picture of this lesion is notable for epileptic seizures and intracerebral hemorrhage. Surgical excision of cavernoma remains the most effective antiepileptic modality. Good results of surgery are achieved with the use of modern operative procedures such as stereotaxy and neuronavigation. MATERIAL AND METHODS: Twelve patients with cavernous hemangioma were operated at the Department of Neurosurgery and Pediatric Neurosurgery, Pomeranian Medical University, Szczecin, between 1999 and 2008. This group included 10 females aged 7-54 years (mean 24.8 years) and 2 males aged 14-49 years (mean 31.5 years), 7 children (58.3%) and 5 adults (41.7%). Seven patients (58.3%) presented with generalized and the remaining 5 patients (41.7%) with secondarily generalized seizures. The mean time from onset of seizures to surgery was 2.6 months. All patients were operated using preoperative neuronavigated mapping to determine the optimal access to the lesion followed by neuronavigation-guided cavernoma excision. Postoperative neurological status was assessed with GOS scale and antiepileptic treatment outcome with Engel's scale as modified by Moran. RESULTS: The caveroma was completely removed in each case. Postoperative follow-up time was 2-59 months (mean 30.3 months). Neurological status of all patients was category 5 of the GOS scale. Engel's class I outcome was achieved in all patients. Nine patients (75%) were weaned off antiepileptic drugs following normalization of EEG. CONCLUSIONS: The following conclusions were drawn basing on the findings of this study: (1) Neuronavigation offers high precision and low traumatization which reduce the risk of neurological sequellae (neurological deficits and epilepsy) in patients operated for cavernoma; (2) Early resection of cavernoma offers the chance of curing epilepsy. PMID- 20349593 TI - [Erythematotelangiectatic skin--diagnostic difficulties]. AB - Erythematotelangiectatic skin is a common cosmetic and medical problem. Flushing or persistent erythema, teleangiectasias, and occasionally other inflammatory skin lesions can be caused by internal or environmental factors. Certain physiologic reactions and systemic or dermatologic diseases represent internal conditions leading to visible skin flushing in the blush area. Erythematotelangiectatic skin is found in body areas which are particularly exposed to various environmental factors and perform important esthetic functions at the same time. Determination of the main etiopathologic factor responsible for flushing in the blush area precedes the selection of an adequate method of care, correction or treatment of the erythematotelangiectatic skin. The main aim of this study was to analyze fundamental mechanisms of flushing or persistent erythema and their sequellae basing on the literature. Another aim was to review current diagnostic options useful in examining the etiology and severity of erythematotelangiectatic skin symptoms. PMID- 20349594 TI - [Assessment of anxiety in women during puerperium]. AB - PURPOSE: Many women experience various emotional disorders during puerperium characterized by high levels of anxiety. THE AIM OF THIS STUDY: To analyse the level of anxiety in women during puerperium depending on age, education, marital status, number of pregnancies, route of delivery, and family situation. MATERIAL AND METHODS: We enrolled 120 women between day 10 and 15 of puerperium without any previous psychiatric disorders. Pregnancy, delivery, and puerperium were without any morbidity and the newborns were healthy. The level of anxiety was measured using C. D. Spilberger's State-Trait Anxiety Inventory (STAI). RESULTS: The level of anxiety as a trait in women during puerperium was within normal limits, whereas the level of anxiety as a state was elevated. Primipara and women up to 20 years of age require special attention during psycho-preventive treatment due to increased level of anxiety as a trait during puerperium. Employment and family situation determine the level of anxiety as a state after delivery. CONCLUSIONS: Identification of women with a higher level of anxiety as a state during puerperium may provoke early medical intervention in this group of women and thus contribute to improvement in the quality of life of the woman and conditions for future development of the neonate. PMID- 20349595 TI - [Frequency and etiology of noncarious cervical lesions with pulp exposure]. AB - PURPOSE: Noncarious cervical lesions have a multifactorial etiology encompassing occlusal trauma, toothbrush abrasion, and exposure of enamel to erosive factors. The purpose of this study was to determine the frequency of cervical lesions with exposure of pulp and to analyze their etiology. MATERIAL AND METHODS: The study was done in 124 patients (59 women and 65 men) with a mean age of 44 years (15-72 years). Clinical assessment of cervical lesions was based on criteria of the universal tooth wear index for the cervical surface. Additionally, the following findings were recorded: frequency of cervical lesions depending on tooth type, pulp exposure, oral hygiene status, and type of occlusal guidance. The questionnaire consisted of detailed questions concerning toothbrushing, frequency of consumption of some foods, and parafunctional habits. The risk of cervical lesion was estimated with the logistic regression model. RESULTS: The frequency, localization, and depth of noncarious cervical lesions were related to age of the patient. Very deep defects with pulp exposure were found in 44 teeth. The effect of consumption of acid foods and drinks and of oral hygiene habits on the depth of wedge-shaped defects was corroborated. Correlations between lateral excursive tooth contact, bruxism, and formation of cervical lesions were disclosed, confirming the relationship between occlusal pathology and cervical lesions. CONCLUSIONS: Elucidation of the multifactorial etiology of cervical lesions is important for proper treatment and prevention of pulp exposure. PMID- 20349596 TI - [Response of dental pulp to self-etching adhesive systems used in indirect capping. A literature review]. AB - OBJECTIVE: To review the literature on dental pulp responses to self-etching adhesive systems used in indirect capping. MATERIAL AND METHODS: Many studies in vitro and in vivo focused on biocompatibility of the self-etching adhesive system used in deep defects. Clinical and radiographic findings from animal and human studies are compared and discussed. RESULTS: Self-etching adhesive systems may be useful when applied to dentin. The results in animal studies cannot be extrapolated directly to humans. Many studies in vitro have shown that components of self-etching adhesive systems exhibit cytotoxic effects in contact with cell cultures. CONCLUSIONS: The reaction of dental pulp to self-etching bonding agents depends on the depth of defect, type of agent, and method of application. PMID- 20349597 TI - [Solving esthetic problems of coronoradicular metal posts in anterior teeth. Case report]. AB - Interest in esthetic dentistry is growing recently. Patients visit dental offices not only to exchange fillings or perform bleaching, but often to demand replacement of unaesthetic prosthetic crowns. Problems appear when dealing with a prosthetic crown of an anterior tooth reinforced with a coronoradicular metal post. Firstly, there exists the risk of color mismatch of the all-ceramic crown due to the old coronoradicular post. Secondly, dark coloration of gum tissues may appear and prove particularly worrisome for a patient with a high lip line. In some cases, root canal retreatment may be necessary due to incomplete root canal filling, apical periodontitis, or interference between filling material and future adhesion of the fiber post to root dentin. This article is a case report describing coronoradicular metal post removal with ultrasound. Indications and contraindications for the procedure are discussed. PMID- 20349598 TI - [Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women]. AB - INTRODUCTION: The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. MATERIAL AND METHODS: Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. RESULTS: Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. CONCLUSIONS: MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas. PMID- 20349599 TI - Treatment of alcoholism in Germany. AB - Alcohol dependence is associated with a wide range of physical, mental, and social harms. The related economic and social costs can be reduced by an adequate addiction therapy. This therapy should not only focus on the psychotherapy of addiction but should also include the possibility to treat psychiatric co morbidity and take into account gender-specific aspects of addiction. The first steps of reintroducing the patient to employment are also of major importance especially in areas of high jobless rates. A highly efficient system of addiction treatment has evolved in Germany over the past decades. Ambulant treatment centers, units offering "qualified alcohol withdrawal programs", and inpatient addiction therapy programs are closely interlinked with each other. The Friedrich Petersen-Klinik in Rostock is presented as an example. The therapeutic needs of the patients and the social situation of north-eastern Germany are reflected in the concept of the Clinic. It is shown how the Friedrich-Petersen-Klinik integrates with other therapeutic modalities to ensure a continuous attendance over many months on the patient's way to stable abstinence. PMID- 20349600 TI - [Body image as a process or object and body satisfaction]. AB - INTRODUCTION: This work focused on categorization of elements of body image viewed as an object or process, as well as on the relationship between body satisfaction and manner of perceiving the body. MATERIAL AND METHODS: The study was carried out in 177 subjects aged 19 to 53 years (148 females and 29 males). Body image was measured with the Body Image Questionnaire based on the Body Cathexis Scale of P.F. Secord and S.J. Jourard. Participation was anonymous. The procedure of attributing an element of the body to the function scale or body parts scale was based on the method described by S. Franzoi. CONCLUSIONS: Elements of body image recognized as body parts were characterized in the context of appearance (static object), while elements of body image recognized as body functions were considered in the context of operation (dynamic process). This relationship, however, was not symmetrical as elements of the body not characterized as body functions could also be evaluated in the context of operation. The level of body satisfaction was associated with perception of an element of the body in the aspect of appearance or operation, whereas its perception as body part or body function was of lesser importance. PMID- 20349601 TI - Beyond purely ethical understanding of responsibility: a phenomenological approach. AB - BACKGROUND: The assumption that moral responsibility is a constitutive feature of the human person could almost be considered as the raison d'etre of ethics and consequently of bioethics. In fact, the concept of"common morality", which is becoming ever more popular within the mainstream of bioethics, assumes that certain, even if elementary, experience of moral responsibility (and understanding of it) is shared by all the people of every cultural (moral) tradition. Although the phenomenon of (moral) responsibility is seen as a moral question, its ultimate explanation needs reflection which goes beyond purely ethical considerations. MATERIAL AND METHODS: The phenomenological ontology as elaborated by R. Ingarden is accepted as the theoretical background of deliberations in this study. Methods of reasoning appropriate to this approach to phenomenology are used. RESULTS AND DISCUSSION: The phenomenon of human responsibility is analyzed--according to Ingarden's suggestion--from the point of view of the four "situations" in which responsibility appears: (I) to be responsible for something, (II) to accept responsibility for something, (III) to be called to responsibility for something, and (IV) to be acting responsibly. The ontological foundation of responsibility in each of these situations is then inquired. Ingarden's philosophical reflection leads to discovery of the ultimate ontological foundation of responsibility in: (I) objective axiology, (II) structure of an acting subject, and (III) a causality structure of reality. We discuss whether Ingarden's analyses are coherent with the concept of "common morality". CONCLUSION: Although R. Ingarden is best known, especially to English speaking readers, for his work in aesthetics, it should be emphasized that his phenomenological ontology can provide interesting insights into the understanding of the concept of responsibility which is fundamental to ethics/bioethics. PMID- 20349602 TI - [What nurses with a bachelor of nursing degree know about the classification of arterial blood pressure and sequellae of arterial hypertension]. AB - INTRODUCTION: Arterial hypertension is among the most important risk factors of atherosclerosis and associated cardiovascular pathology with a prevalence rate estimated at 20-30% of the adult population. Nowadays, it is recommended to perform an individual assessment of cardiovascular risk in a patient and to determine the threshold value for arterial hypertension, even though blood pressure classification values according to the European Society of Hypertension and the European Society of Cardiology (ESH/ESC), as well as the Polish Society of Hypertension (PTNT) have remained unchanged. AIM OF STUDY: To determine what nurses with a Bachelor of Nursing degree know about the prevalence and classification of arterial blood pressure, as well as sequellae of arterial hypertension. MATERIALS AND METHODS: This study was done in 116 qualified nurses (112 females, 4 males; age 21-50; seniority 0-29 years). The research period was from June 2007 to January 2008. The research tool was a questionnaire devised by the authors. RESULTS: We found that half (on the average) of those questioned have an up-to-date knowledge regarding classification of blood pressure and prevalence of arterial hypertension but just one out of three respondents (on the average) was able to describe its sequellae. Relatively less known among nurses with a Bachelor of Nursing degree were aspects of "white coat hypertension". Statistically significant differences regarding correct answers were noted depending on seniority (p = 0.002), place of work p < 0.001), or position (p < 0.001). There were no differences depending on age, place of residence, marital status, or form of postgraduate education of nurses with a Bachelor of Nursing degree. CONCLUSION: It is necessary to improve knowledge among students of nursing (BN degree) about current classification of blood pressure, as well as prevalence of arterial hypertension and its sequellae. PMID- 20349603 TI - [Origin and development of dental surgery and oral and maxillofacial surgery in Western Pomerania between 1951 and 2001]. AB - The aim of this thesis was to present the history of dental surgery and oral and maxillofacial surgery in Western Pomerania after World War II. It was shown that these related fields developed dynamically at the Pomeranian Medical University in Szczecin resulting in the transformation of the Chair and Department of Dental Surgery into two independent units: Chair and Department of Oral and Maxillofacial Surgery and Chair and Department of Dental Surgery. Both departments provided mainstream health care for the population of Szczecin and its suburbs in the field of dental surgery and for the whole Western Pomerania in the field of oral and maxillofacial surgery. By engaging in scientific, didactic, and social activities, these departments greatly contributed to the development of dental surgery and oral and maxillofacial surgery in Western Pomerania. The Department of Oral and Maxillofacial Surgery is among the leading institutions in Poland offering oncologic treatment encompassing the facial part of the skull. PMID- 20349604 TI - [How much good, how much bad in a small word Glossa]. PMID- 20349605 TI - [The influence of immunosuppression on vancomycin concentration in the rat allogenic lung transplant]. AB - AIM: To assess the influence of conventional immunosuppression on vancomycin concentration in the rat allogenic lung transplant basing on acute and hyperacute rejection models. MATERIAL AND METHODS: Left lung allotransplantations were performed from Brown Norway donors to Fisher F 344 recipients in the acute rejection model (animals were sacrificed 5 days after transplantation), and from Brown Norway donors to Wistar recipients in the hyperacute rejection model (animals were sacrificed 2 days after transplantation). Immunosuppression (cyclosporin A 5 mg/kg b.w., aziathioprine 4 mg/kg b.w., methylprednisolone 4 mg/kg b.w.) was administered daily. Control rats received no immunosuppression and were sacrificed on day 2 or 5, respectively. Rejection grading was done on the basis of arterial pO2 and histology of the lung graft sample obtained at autopsy. A single 30 mg/kg b.w. dose ofvancomycin was injected intraperitoneally on day 2 or 5 depending on the model. Samples of blood and grafted lung were collected 30 min, 1 h, 2 h, 4 h, and 6 h from injection. RESULTS: Arterial pO2 levels were significantly higher in the group with acute rejection and immunosuppression as compared with the control groups. Histology revealed attenuated rejection in the immunosuppression groups. Vancomycin concentration in the transplanted lung and the lung graft to plasma vancomycin concentration ratio did not differ in the immunosuppression and control groups. CONCLUSIONS: Immunosuppression has no influence on vancomycin concentration in the transplanted lung. PMID- 20349606 TI - The role of iron in metal-metal interactions in hard tissues of roe deer (Capreolus capreolus L.). AB - INTRODUCTION: The toxicity of heavy metals in humans and animals has been attributed to their potential for accumulation in solid tissues and interference with other vitally important elements present in the body. We have devised this study to determine the content of some metals in bone and to determine with the Statistica Neural Networks program whether the content of one metal has any effect on the content of other metals. MATERIAL AND METHODS: Our material consisted of mandibles obtained from deer aged 2 to 6 years. Using a dental drill, pulverized bone was obtained for measurements of calcium, copper, and zinc with atomic absorption spectrometry and magnesium, chromium, manganese, and iron with inductively coupled plasma atomic emission spectometry. Statistical analysis was performed with the Statistica software and its Statistica Neural Network program. RESULTS: We found that the concentration in bone of one metal affects the concentrations of other metals. CONCLUSIONS: Iron seems to play a special role in the accumulation of other metals by bone. The use of artificial neural networks was helpful in identifying candidate elements (like iron) which are active in controlling concentrations of other metals in bone. PMID- 20349607 TI - CD52 gene polymorphism and its potential effect on the response to alemtuzumab in renal transplant recipients. AB - CD52 is a small glycopeptide leukocyte antigen present on selected subpopulations of human cells. From the clinical point of view this protein is an important target for therapeutic interventions aimed at leukocyte depletion in hematological malignancies and post-transplant immunosuppression. Recently, two variants of CD52--rs1071849 (A119G; Asn40Ser) and rs17645 (A123G; I1e41Met)--were discovered. We now report on the distribution of these variants in kidney graft recipients and controls. Our bioinformatics findings suggest that CD52 polymorphism may affect the efficiency of GPI anchor formation and thus may indirectly alter the response to anti-CD52 agents. PMID- 20349608 TI - Arteriovenous fistula: a rare complication of nephrectomy in a child with Wilms tumour. AB - The case of a 13-year-old boy with a renal arteriovenous fistula in the left renal pedicle after nephrectomy is presented. The fistula was successfully managed by percutaneous transluminal embolization with coils sparing the patient the burden of surgery. Attention is drawn to the very rare incidence of this complication after nephrectomy in children with Wilms tumour. PMID- 20349609 TI - [Incidence and risk factors of lymphedema in women after surgery for breast cancer]. AB - INTRODUCTION: Epidemiologic data for the last decade reveal increasing incidence of female breast cancer in Poland. One of the serious therapeutic consequences in breast cancer is secondary lymphedema of the upper extremity which significantly affects the quality of life. The aim of this study was to assess the incidence and to identify risk factors of lymphedema after breast cancer surgery. MATERIAL AND METHODS: Lymphedema and its severity were studied on the basis of anamnesis, clinical examination, and optoelectronic measurement of limb volume. The study group consisted of 246 women after breast cancer surgery. CONCLUSIONS: Lymphedema was observed in 40.6% of women. The most important risk factors for lymphedema include previous infections, radiotherapy, and obesity. PMID- 20349610 TI - [Self-care and demand for social support in women with infertility]. AB - INTRODUCTION: The prevalence of infertility among married couples is growing. It is estimated that every fifth married couple in Poland is infertile. Infertility is often a source of significant stress for the spouses. It is therefore important to provide professional support, demonstrate interest, listen to the problem, and be present in difficult moments. Social support considerably reduces the feeling of abandonment, fosters self-care, accelerates recovery, strengthens coping, and helps modify views and habits or attitudes towards treatment. The aim of this study was to assess self-care in women with infertility and to identify the most common sources of social support. MATERIAL AND METHODS: The study group consisted of 100 women diagnosed or treated for infertility at the Department of Reproduction and Gynecology, Pomeranian Medical University in Szczecin. The diagnostic poll was done with the aid of a standardised research tool--the Social Support Scale Questionnaire by Danuta Zarzycka. The study protocol was approved by the Bioethics Committee of the Pomeranian Medical University. The study was performed between July 2005 and March 2007. CONCLUSIONS: (1) Self-care in women with infertility is adequate. (2) Women with infertility usually expect professional support from a physician; the role of the nurse is undervalued. Thus, the role of the nurse and midwife needs further promotion. PMID- 20349611 TI - [A comparison of the results of treatment in young and elderly patients with chronic subdural hematoma depending on the method of surgery]. AB - INTRODUCTION: Chronic subdural hematoma (CSDH) generally occurs in patients past the age of 50 years but may develop at any age, also in young persons. The aim of this study was to compare the results of treatment in young and elderly patients with CSDH depending on the method of surgery: burr hole (group A) or craniotomy (group B). MATERIAL AND METHODS: This retrospective study was based on medical histories and computed tomography findings in patients with CSDH operated at the Department of Neurotraumatology, Jagiellonian University, in 1983-2003. Altogether, 114 patients were analyzed including 35 (30.7%) patients under the age of 40 years and 79 (69.3%) patients over the age of 75 years. RESULTS: A significant correlation between the result of treatment and age of patients with CSDH was demonstrated. The best result (Glasgow Outcome Scale = 5) was achieved in 73.9% of young patients in the trepanation group and in 66.7% in the craniotomy group as opposed to just 15.5% of elderly patients in the trepanation group and 4.8% in the craniotomy group. The difference between young and elderly patients was significant (p = 0.00001 for burr hole surgery, p = 0.0006 for craniotomy). Burr hole evacuation offered better results than craniotomy. CONCLUSIONS: (1) The results of treatment were much better in young than in elderly patients. (2) Comparison of the results of treatment of chronic subdural hematoma shows that burr hole surgery is the preferable procedure. PMID- 20349612 TI - [Chronic subdural hematoma: a review of the literature. Part 1]. AB - The first part of this publication is a review of the literature on the history, etiopathogenesis, clinical signs, and diagnosis of chronic subdural hematoma (CSDH). The incidence rate of CSDH is 2-11 cases per 100000 inhabitants. In spite of many anatomopathologic and biochemical studies, the pathomechanism of CSDH has not been fully explained. Although head computed tomography is the method of choice for the diagnosis of CSDH, magnetic resonance imaging can provide much more structural information on the hematoma. The pathophysiology of mental changes and hemiparesis in CSDH remains unclear. However, disturbances of cerebral haemodynamics seem to play a major role. PMID- 20349613 TI - [Strategies for posterior teeth reconstruction after endodontic treatment: a case report]. AB - Reconstruction of hard dental tissue after endodontic treatment is a difficult and important duty of the dentist. According to the general opinion, endodontically treated teeth are inferior in quality, more brittle, predisposed to fractures and cracking. Logically, such teeth require reconstruction to prevent fractures, cracks, and bacterial microleakage leading to reinfection. The procedure of choice in the nineties of the 20th century was restoration with a metal post and prosthetic crown. Advances in materials resulting in improved adhesion to hard dental tissue have prompted a change in the reconstruction strategy for posterior teeth after endodontic treatment. In the case of molars, the crown can be restored with composite materials thanks to additional retention offered by the chamber of these teeth. The recommendation for premolars is to reinforce them with a glass fiber post. We now present a case which illustrates the actual trends in reconstruction of posterior teeth after endodontic treatment. PMID- 20349614 TI - [Lincomycin applied to the alveolus on TCP carrier and its effect on wound healing after surgical extraction of a third molar]. AB - INTRODUCTION: The dental surgeon is often confronted by complications particularly after extraction ofunerupted lower third molars. The most common complication is alveolar periostitis. The healing process after extraction is accompanied by physiologic atrophy of the alveolus involving on the average 30% of bone tissue. Beta-tricalcium phosphate (TCP) is a synthetic material used in medicine to fill up bone defects caused by pathologic processes. The properties of TCP are appropriate for the material to be used as a carrier for drugs, in particular antibiotics. This study was undertaken to determine whether lincomycin applied to the alveolus on TCP carrier can be used to accelerate wound healing and reduce inflammation after surgical extraction of a third molar. MATERIALS AND METHODS: We enrolled 80 patients (males and females between the age of 18 and 50 years) who underwent extraction of a third molar at the Department of Dental Surgery, Pomeranian Medical University in Szczecin. Surgical difficulty in the patients according to the Pederson scale corresponded to grade 2 or 3 (medium or high difficulty). The study group consisted of 40 patients who received lincomycin on TCP. Beta-tricalcium phosphate (300-700 microm pores) obtained from the Department of Technology of Ceramics and Refractories, AGH University of Science and Technology in Cracow, was soaked with 500 mg of lincomycin in solution and applied to the dental alveolus after tooth extraction. The alveolus was tightly sutured. The control group comprised 40 patients not treated with lincomycin. The patients reappeared for examination on the first, third, and seventh day after surgery. Attention during follow-up was directed to alveolar periostitis, pain, and trismus. Pain intensity was assessed with the 10-degree Visual Analog Scale (VAS). RESULTS: We analyzed the subjective pain intensity reported during follow-up by the patients. In the study group, 20 patients reported no pain 24 hours after extraction. On the third day after surgery, alveolar periostitis was present in 15% of patients in the study group and 75% of patients in the control group. On the last day of follow-up, periostitis was present in only 2.5% of patients in the study group as opposed to 45% of patients in the control group. The differences were statistically significant (chi-square 36.05, p < 0.0001). CONCLUSIONS: (1) Lincomycin on TCP can be used to prevent alveolar periostitis. (2) Lincomycin on TCP reduces complications in the form of pain and trismus. (3) Beta-tricalcium phosphate prevents atrophy of the alveolar process. PMID- 20349615 TI - [Dentinal hypersensivity after vertical stripping of enamel]. AB - INTRODUCTION: Vertical stripping of enamel in patients with minor or moderate crowding of teeth and Angle's class I is an effective method which supplements orthodontic treatment. Stripping is an alternative to tooth extraction or to extension of alveolar arches which carries the risk of recurrence of crowding and further periodontal difficulties. Stripping also shortens considerably the duration of treatment. Apart from unquestionable advantages, enamel reduction may lead to complications such as caries or hypersensitivity of interproximal surfaces of stripped teeth. The aim of this study was to determine the prevalence of hypersensitivity and to measure the intensity of pain. MATERIALS AND METHODS: We performed a verbal and visual assessment of pain in a group of 32 patients who underwent stripping during the recent few years as part of orthodontic treatment. RESULTS: According to verbal assessment, the highest percentage (46.9%) of patients rated their pain as 1 (gentle pain) which corresponded to 1-3 cm on the 10 cm Visual Analog Scale. 37.5% of patients reported no pain. CONCLUSION: None of the patients described their pain as very strong and discouraging from further treatment. All symptoms subsided without recurrence. The patients found this method to be more effective than alternative ones. PMID- 20349616 TI - Microscopic evaluation of the tooth-bond-composite interface. Images from SEM. Preliminary report. AB - INTRODUCTION: Systems that bond composite material to enamel are constantly modernized (application is simplified and the number of system components is reduced). The latest products are one-coat systems combining etchant, primer, and bond. Use of such systems is easier for the dentist and adds to patient's comfort. The aim of this work was to evaluate microscopically the composite material--bond-enamel interface in a tooth processed with an abrasive technique. MATERIAL AND METHODS: The material comprised premolar human teeth extracted for orthodontic reasons. Cavities reaching the enamel-dentin border were created on the buccal surface of the teeth with the dental-prosthetic micropreparator (MSP). A self-etching Adper Prompt L-Pop system was applied (separate use of etchant was unnecessary). Bond application was according to manufacturer's recommendations. The cavities were filled with Point composite material from Kerr. Tooth samples were placed in the chamber of JEOL JSM 5500 LV scanning electron microscope and images were obtained at 15 kV. Strong bonding at the composite material-bond interface was observed as evidenced by the melting of composite particles into the self-etching bonding system. PMID- 20349617 TI - Orthodontic treatment of a patient with severe class II malocclusion, bony fibrous dysplasia, root resorptions, and missing four premolars. AB - INTRODUCTION: A case of distal occlusion is presented with root resorptions and missing premolars, treated at the end of the growth period with Herbst appliance. Orthodontic treatment in non-progressive fibrous dysplasia is assessed. MATERIAL AND METHODS: Anamnesis, results of extraoral and intraoral examinations, typodonts, panoramic view, hand-wrist radiogram, and cephalogram were obtained in a 14-year-old boy with severe distal occlusion, root resorptions resulting from previous orthodontic treatment, fibrous dysplasia of bone, and missing four premolars. Successful treatment was achieved with Herbst appliance followed by fixed appliances. RESULTS: Bands were placed on upper second molars and lower first premolars and the Herbst appliance was positioned forcing the mandible forward. After three months the patient was unable to position the mandible backwards. Canine and Angle Class I were achieved, overjet and overbite were reduced to 2 mm. Lower face height was reduced and the upper lip was retracted, producing lip competence. At this point the fixed appliances were removed, an upper removable retention plate was made, and a lower flexible spiral wire retainer was bonded. Active retreatment lasted 15 months. No hypermobility of any teeth nor progression or neoplastic transformation of fibrous dysplasia were noted at the end of orthodontic treatment. CONCLUSIONS: (1) It is possible to treat distal occlusion with Herbst appliance at the end of the growth period. (2) Root resorptions are not a contra-indication to treatment if potential benefits outweigh risks. (3) Orthodontic tooth movement appears possible and safe in patients with non-progressive fibrous dysplasia. PMID- 20349618 TI - [What nurses with a bachelor of nursing degree know about the effects of alcohol on blood pressure and risk of arterial hypertension]. AB - INTRODUCTION: Alcohol abuse is one of the main causes of arterial hypertension. Alcohol is responsible for a few to more than ten percent of all cases of primary hypertension, particularly in persons consuming more than 20-30 g of alcohol per day. The aim of this study was to find out what Bachelor of Nursing degree holders know about alcohol consumption styles and the effects of alcohol on blood pressure, as well as on the risk of arterial hypertension in adults. MATERIAL AND METHODS: The study group comprised 116 qualified nurses (112 females, 4 males; age 21-50 years; work seniority 0-29 years). The study was done between June 2007 and January 2008 with the use of the diagnostic poll technique based on a questionnaire developed by the authors. RESULTS: We found that 8.62% of participants were informed about screening tools used for evaluating styles of alcohol consumption while 41.38% gave the correct definition of the standard portion of alcohol. The alcohol consumption threshold above which the risk of hypertension becomes significant was known to 58.62% of respondents. The influence of alcohol (drunk directly before blood pressure measurement) on blood pressure was known to 89.66% of the nurses. We observed a statistically significant effect of work experience (p = 0.002), place of work (p < 0.001), and position held (p < 0.001) on the number of correct answers. No statistically significant differences depending on age, place of residence, family status or type of postgraduate education were noted. CONCLUSION: It is necessary to increase awareness among nurses regarding the risk of arterial hypertension associated with alcohol consumption and to improve the effectiveness of undergraduate and postgraduate education aimed at early recognition of problems caused by alcohol consumption which are important for the prevention of arterial hypertension. PMID- 20349619 TI - [Length of service as a nurse: continuing to burnout?]. AB - INTRODUCTION: Medical professionals are particularly exposed to stress. It is therefore important for them to learn how to cope with work stress and prevent burnout. This study was undertaken in a group of nurses from the province of Kuyavia and Pomerania to determine the extent to which strategies and attitudes required for work effectiveness change with length of service. MATERIAL AND METHODS: Four groups were formed according to seniority: up to 15 years, 16-20 years, 21-25 years, and more than 25 years at work. The survey instrument was the AVEM questionnaire consisting of scales which cover the following personality domains: commitment to service, resistance to stress, problem-solving strategies, emotional well-being at work. The results were analyzed basing on percentile norms for hospital staff. RESULTS: It was found that career ambitions and offensive problem-solving strategies correlate with length of service. Nurses with the shortest length of service were least active in coping with problems. Competence increased with seniority. The distribution of results regarding career ambitions was greatest in group 3 (15-25 years at work). It seems plausible that on the one hand this finding can be attributed to seniority, on the other to different social roles undertaken concurrently. CONCLUSIONS: Qualitative assessment of the present results demonstrated that commitment to service is important for nurses regardless of work experience. This study did not take into account the total personality structure as a modifying variable which determines the direction of personal development, including professional development, and integrates human activities. PMID- 20349620 TI - [The physician-patient relationship in the context of the attachment theory]. AB - This work presents the application in medical practice of relationship rules derived from the theory of attachment which was first formulated in the fifties by John Bowlby, a British psychiatrist, and further developed by the American developmental psychologist Mary Ainsworth. This theory is considered to be one of the more outstanding achievements of psychology in the 20th century. Attachment types may reveal themselves in the form of specific behavior which characterizes the relationship of the patient with medical staff. The reaction to stress is shaped by the experience of childhood during which the child develops and perpetuates its own style of emotional expression and coping with stress. The child's model of coping with stress matures along with the experience of care from adult caregivers and determines the future pattern of coping with strange situations and solving problems through open communication and "accommodation" of negative or distressing emotions during therapy. PMID- 20349621 TI - [The problem of usefulness of the philosophical concept of disease in medicine]. AB - This work focuses on contemporary discussions devoted to the general concept of disease and its relevance to clinical practice. Some authors (e.g., Hesslow) argue against a key role of the general concept of disease in clinical decision making. Other authors (Pellegrino, Clouser, Culver, and Gert) emphasize the significance of the concept of disease in public health and in the methodology of medical practice. PMID- 20349623 TI - TJC report shows quality continues to improve. AB - Cardiac, pneumonia care see significant boosts in compliance rates. Highly reliable care is a major goal of The Joint Commission. When curve "flattens out," other areas of focus should be considered. PMID- 20349622 TI - Health system sets 'zero errors' as its goal for patient safety, quality. AB - Small percentage "gaps" can mask large numbers of errors. Hard wiring processes can speed up, enhance improvement. Use family members as standard for "acceptable" risks. PMID- 20349624 TI - Research looks at children in the ED. AB - Groups come together to create guidelines for pediatric population in EDs. One of the more creative proposals involves the establishment of two new positions in the ED: a physician coordinator and a nurse coordinator. The medical director, nursing director should be hospitalwide liaisons. PMID- 20349625 TI - Lack of adherence in heart failure therapy. PMID- 20349626 TI - Tips on long-term steps to improve discharge planning. PMID- 20349627 TI - [Parasite fauna and features of the parasite community structure in the minnow Phoxinus phoxinus (Linnaeus) from Yenisei and Kacha rivers]. AB - Phoxinus phoxinus is a species widely distributed throughout Palaearctic and is a good model for investigation of parasite communities. Species composition and structure of parasite communities in the minnow from the streams if different types, namely Yenisei river near Krasnoyarsk City and its left affluent Kacha River, were examined. Indices of Shannon, Simpson, and Berger-Parker were used to describe the component parasite communities. Twenty five parasite species of seven classes were revealed, and ectoparasite were found to be dominating among them. The host-specific parasite species Paratrichodina phoxini (Infusoria), Dactylogyrus borealis (Monogenea), Parahemiurus merus and Diplostomum phoxini (Digenea) constitute the peculiarity of the parasite fauna in minnow. Parasite community of minnow in the Kacha river is the most various one. It is caused by the following factors--favorable temperature conditions, composition of ichthyofauna, and a high density of fish population in the Kacha river. Metacercaria of Diplostomum phoxini, the specific parasites of minnow's brain, are dominating in both streams. PMID- 20349628 TI - [Morphogenesis of the Staphylocystis furcata cysticercoid (Cyclophyllidea, Hymenolepididae)]. AB - The morphogenesis of the Staphylocystis furcata (Stieda, 1862) cysticercoids has been studied in the experimentally infected beetles Geotrupes stercorosus and their structural and ontogenetic features have been described. At the initial stage of its development metacestode of S. furcata forms lacuna primitiva. The primordium of scolex invaginates early into the posterior part of the larva, and then the scolex develops in the cyst cavity. There is only an anterior obturator valve developing in the cyst. Posterior obturator valve is absent, that results in the cyst remaining unlocked and the cercomer does not separate from the cyst. There is no lacuna primitiva in the cercomer. The tegument of metacestode gets covered with a solid fibrous layer at the final stage of morphogenesis. It makes the cyst partly or completely pressed in the anterior part of the cercomer when it grows. The similarity between S. furcata cysticercoids and morphologically related cysticercoids Hymenolepididae has been analysed. PMID- 20349629 TI - [Helminthofauna of reptiles in the Republic of Belarus]. AB - Analysis of original long-term investigation (1980-2006) and literary data on the helminthofauna of reptiles in the Republic of Belarus is carried out. Seven species of reptiles were examined on Southern Belarus, 32 species of helminthes were found with total infestation 72.7%. It is established that the helminthofauna of reptiles in the Republic of Belarus includes 33 species (18 trematodes, two cestodes, 12 nematodes, and one acanthocephalan). The largest number of helminth species (26) was recorded in the common water snake Natrix natrix, and the least number of species (four) was recorded in the turtle Emys orbicularis and snake Coronella austriaca. PMID- 20349631 TI - [Peculiarities of the distribution of freshwater Myxosporea in the European part of palaearctic]. AB - The complete taxonomic composition (158 species of freshwater Myxosporea inhabiting European Part of Palaearctic is presented. Their distribution by faunistic complexes and groups is established. Analysis of similarity between myxosporean faunas by zoogeographical areas and districts is carried out. Historical background of the distribution and formation of the freshwater myxosporean fauna is discussed. PMID- 20349630 TI - [Distribution of Aspidogaster conchicola (Aspidogastrea, Aspidogastridae) in the organism of Colletopterum spp. (Bivalvia, Unionidae) of different age from the Chivyrkuiski Gulf of Lake Baikal]. AB - Distribution of Aspidogaster conchicola Baer, 1827 in the organisms of its hosts Colletopterum spp. from the Chivyrkuiski Gulf of Lake Baikal was investigated. The number of A. conchicola in the organism of Colletopterum spp. was found to decrease along the row pericardial cavity-mantle cavity-gills-kidney. The pericardial cavity of Colletopterum spp. is the most favorable habitat for A. conchicola with 72% of the helminthes parasitizing in it. In the pericardial cavity the largest number (61%) of A. conchicola was found in its posterior part. PMID- 20349632 TI - [Study of the monogenean family Tetraonchidae Bychowsky, 1937 by the scanning electron microscopy]. AB - Hitherto data on the morphology of Tetraonchidae and their eggs obtained with scanning electron microscopy (SEM) were absent in the literature. In the present paper results of SEM study of two genera of Tetraonchidae, Tetraonchus and Salmonchus, are given. Fine morphological traits of eggs, larvae, and definitive individuals of Tetraonchidae, as well as patterns of their attachment to host gill, were established for the first time. A deep penetration of the worms into the branchial epithelium of the host was shown. PMID- 20349633 TI - [Influence of trematode invasion and zinc ions on the histometric peculiarities of haemocytes and some hematological indices of Planorbarius purpura (Gastropoda: Pulmonata: Bulinidae)]. AB - Cellular components of the Planorbarius purpura hemolymph are represented by three phyla of haemocytes (prohemocytes, eosinophilis microgranulocytes, and basophilis granulocytes) and vesicular cells. As a result of the invasions of P. purpura with the trematode Echinoparyphium aconiatum, changes of the linear dimensions of granular hemocytes and their nuclei took place. Moreover, an increase of the hemocytes' number per l mm3 of hemolymph and change of the percentages of different hemocyte types were recorded. Under the influence of zinc ions, linear dimensions of prohemocytes and their nuclei (at 10 MPCns of the toxicant) were changed. In granular hemocytes and abnormalities of all histometrical and hematological parameters were observed. All cytometrical, karyometrical, and hematological alterations were expressed more clearly in infested mollusks than in non-infested ones, and occurred usually under lower concentrations of zinc ions. PMID- 20349634 TI - [Tarsal gland of the ticks Ixodes persulcatus and Ixodes ricinus (Ixodidae)]. AB - A complicated multicellular gland is situated in tarsi of all the legs, occupying one third to half of the segment. Glandular cells form a single-layer sack; inner surface of the sack (gland cavity) is enveloped by a multilayer membrane. Cuticular rods connecting muscles with the claw pass inside this cavity. Glandular cells are characterized by the presence of numerous apical microvilli associated with accumulations of mitochondria, and secretory vacuoles enclosed in cellular membranes. The basal part of each cell contains lipid vacuoles and glycogen granules. The possibility of the track contact pheromone's production by the tarsal gland is discussed. PMID- 20349635 TI - [Distribution of fleas in rodent colonies in the northwestern Precaspian region]. AB - Distribution of fleas by their rodents hosts was investigated by field experiments using the method of individual labeling both the parasites and the hosts. The experimental site was situated in sand landscapes of the northwestern Precaspian region. Pattern of the contacts between rodents leading to the exchange of their ectoparasites was established. Average distance of the rodent migration from the site of its previous record was 54 m, while the distance of flea transfer for the same period was 142 m. The probability of host exchange by a flea under under its periodic attacks on host amounted to the value 0.500 0.889. The parameters of flea spreading in the northwestern Precaspian region and in the sand landscapes between Volga and Ural were shown to be similar. The ability of the flea Xenopsylla conformis to parasitizing on social vole without a significant decrease of its abundance was revealed. PMID- 20349636 TI - [Knowing how to whistle]. PMID- 20349637 TI - [Malnutrition in the elderly in health care. Causes, instruments and consequences]. PMID- 20349638 TI - [Preventing progressive immobility in the elderly]. PMID- 20349639 TI - ["Nothing is self evident anymore"]. PMID- 20349640 TI - [An interdisciplinary responsibility]. PMID- 20349641 TI - [With long-term training back into life]. PMID- 20349642 TI - [The annual personnel interview]. PMID- 20349643 TI - [Learning to know, understand and value oneself]. PMID- 20349644 TI - [Survey of nurses about compression therapy of acute deep venous thrombosis. Field study in Saxony-Anhalt]. AB - BACKGROUND: In clinical practice, the compression therapy is an established method for the treatment of acute deep vein thrombosis (DVT). The aim of this study was to clarify the extent to which current guidelines and results of studies done in the field for the treatment of acute DVT--particularly compression therapy--are implemented in clinical practice. METHOD: All hospitals in Saxony-Anhalt using primary diagnosis and therapy for DVT (n = 34) were informed about a survey in 2007 and the nursing staff of angiology and internistical wards in these hospitals was asked to take part. The collection of data was done with the help of a questionnaire that had been designed and tested for its validity in a specialised hospital. 510 questionnaires were distributed. The response rate of questionnaires was 69 percent. RESULTS: 79 percent of the nursing staff of internistical wards in Saxony-Anhalt and 94 percent of the nursing staff of angiology wards said that patients with acute DVT have initially received a compression bandage. Significant deficits were visible in transferring the knowledge of evidence-based medicine and nursing regarding techniques of compression bandage. The recommended Fischer-Bandage was only put on in exceptional cases in internistical wards (3 percent) and Angiology (2 percent). Compression stockings were not a suitable method into the treatment of acute deep vein thrombosis of Angiology. 21 percent of the nursing staff of internistical wards said that they have initially applied compression stockings. CONCLUSION: The treatment of acute DVT is important in clinical practice. The compression bandage should be effectively put on the leg. The quality of care and long-term compliance of the patients could be increased this way, leading to prevention of post thrombotic syndrome (PTS) and reduction the duration of patients stay in the clinics. PMID- 20349645 TI - [The importance of nursing care instruction]. PMID- 20349646 TI - [Discussion in the psychiatric department]. PMID- 20349647 TI - [New kinds of housing and nursing care for the elderly: enforcing consumer protection]. PMID- 20349648 TI - [An appropriate scale is crucial]. PMID- 20349649 TI - [Preventive measures and professional counseling in osteoporosis]. PMID- 20349650 TI - Clostridium difficile and the surgeon. PMID- 20349651 TI - General surgery training at the University of Texas Southwestern Medical Center: a legacy of excellence. PMID- 20349652 TI - Surgical anatomy of the retroperitoneal spaces, Part IV: retroperitoneal nerves. AB - We present surgicoanatomical topographic relations of nerves and plexuses in the retroperitoneal space: 1) six named parietal nerves, branches of the lumbar plexus: iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, obturator, femoral. 2) The sacral plexus is formed by the lumbosacral trunk, ventral rami of S1-S3, and part of S4; the remainder of S4 joining the coccygeal plexus. From this plexus originate the superior gluteal nerve, which passes backward through the greater sciatic foramen above the piriformis muscle; the inferior gluteal nerve also courses through the greater sciatic foramen, but below the piriformis; 3) sympathetic trunks: right and left lumbar sympathetic trunks, which comprise four interconnected ganglia, and the pelvic chains; 4) greater, lesser, and least thoracic splanchnic nerves (sympathetic), which pass the diaphragm and join celiac ganglia; 5) four lumbar splanchnic nerves (sympathetic), which arise from lumbar sympathetic ganglia; 6) pelvic splanchnic nerves (nervi erigentes), providing parasympathetic innervation to the descending colon and pelvic splanchna; and 7) autonomic (prevertebral) plexuses, formed by the vagus nerves, splanchnic nerves, and ganglia (celiac, superior mesenteric, aorticorenal). They include sympathetic, parasympathetic, and sensory (mainly pain) fibers. The autonomic plexuses comprise named parts: aortic, superior mesenteric, inferior mesenteric, superior hypogastric, and inferior hypogastric (hypogastric nerves). PMID- 20349653 TI - Impact of hospital and surgeon volumes in the management of complicated portal hypertension: review of a statewide database in Florida. AB - Mortality after complex surgical procedures has been shown to be inversely related to hospital volume. The purpose of this study was to determine whether these findings are applicable to radiologic and surgical procedures for complicated portal hypertension. The Agency for Healthcare Administration for the State of Florida database was queried to determine outcomes after transjugular intrahepatic stent shunts (TIPS) or surgical shunts from 2000 to 2003. A total of 1486 patients underwent either TIPS (1321) or surgical shunts (165). Natural breakpoints occurred at two and six procedures per year were correlated with survival for surgical shunts but not TIPS. Overall mortality was not different between TIPS and surgical shunts (11.0 vs. 12.7%, P = 0.51); however, the cost of TIPS was significantly lower (62,000 +/- 58.5 vs. 107,000 +/- 97.8, P < 0.001) as well as the length of hospitalization (9 +/- 9.0 days vs. 15 days +/- 12.6 days, P < 0.001). Surgical procedures for complicated portal hypertension are rapidly being replaced by TIPS. Like with other complex procedures, outcomes are related to hospital volume. PMID- 20349654 TI - Surgical treatment of axillary accessory breasts. AB - Accessory breast tissue is a remnant persisting after normal embryological development of the breast. Although accessory breasts may be asymptomatic, they can cause discomfort during menstruation, anxiety, cosmetic problems, pain, or restriction of arm movement. The data of all patients who presented with axillary accessory breasts between January 2000 and September 2008 were recruited from a computer database. Medical charts, outpatient records, operative notes, and pathology reports were reviewed. A total of 29 patients underwent surgical treatment of axillary accessory breasts in the Department of Breast Surgery and Department of Plastic, Reconstructive and Aesthetic Surgery. The ages of the patients at the time of surgery ranged from 19 to 54 years. The mean age was 28.8 years. All patients were female. Sixteen patients had unilateral accessory breast and 13 patients had bilateral accessory breasts. Fourteen patients had breast hypertrophy. Twenty-one patients had excision, five patients had liposuction, and three patients had both. Axillary accessory breasts can be satisfactorily treated with excision, liposuction, or both. In patients with concomitant macromastia, reduction mammaplasty and removal of accessory breasts can be performed at the same time with no additional morbidity. PMID- 20349655 TI - Carcinoid tumors of the appendix: are these tumors identifiable prospectively on preoperative CT? AB - The purpose of this study was to determine if carcinoid tumors of the appendix were identified prospectively on preoperative CT at our institution during the last decade. A surgical database search performed using the Current Procedural Terminology codes for appendectomy and colectomy yielded 2108 patients who underwent appendectomy or colectomy with removal of the appendix from January 1998 through September 2007. Pathology reports were reviewed to identify patients in whom an appendiceal carcinoid tumor was identified. Preoperative CT reports and images were reviewed. Twenty-three carcinoid tumors (1.1%; 15 women [65.2%], eight men [34.8%]; average age 54 years [range, 23 to 86 years]) were identified. Ten patients underwent preoperative CT. No tumors were identified prospectively on CT. Images were available for rereview for eight patients. Studies were acquired with 16- (n = 7) and four- (n = 1) slice CT scanners. Average reported tumor size was 6.1 mm (range, 1.5 to 15 mm; n = 18). A tip or distal location was reported for all tumors for which a location was given (n = 15). Carcinoid tumors occurred in 1.1 per cent of appendix specimens. These tumors were all less than or 1.5 cm in size. Likely as a result of their small size, none of these tumors was identified prospectively on preoperative CT. PMID- 20349656 TI - Percutaneous versus open tracheostomy in the pediatric trauma population. AB - The purpose of this study was to determine the safety and efficacy of percutaneous versus open tracheostomy in the pediatric trauma population. A retrospective chart review was conducted of all tracheostomies performed on trauma patients younger than 18 years for an 8-year period. There was no difference in the incidence of brain, chest, or facial injury between the open and percutaneous tracheostomy groups. However, the open group had a significantly lower age (14.2 vs. 15.5 years; P < 0.01) and higher injury severity score (26 vs. 21; P = 0.015). Mean time from injury to tracheostomy was 9.1 days (range, 0 to 16 days) and was not different between the two methods. The majority of open tracheostomies were performed in the operating room and, of percutaneous tracheostomies, at the bedside. Concomitant feeding tube placement did not affect complication rates. There was not a significant difference between complication rates between the two methods of tracheostomy (percutaneous one of 29; open three of 20). Percutaneous tracheostomy can be safely performed in the injured older child. PMID- 20349657 TI - The aging road warrior: national trend toward older riders impacts outcome after motorcycle injury. AB - Industry statistics suggest that motorcycle owners in the United States are getting older. Our objective was to analyze the effect of this demographic shift on injuries and outcomes after a motorcycle crash. Injured motorcyclists aged 17 to 89 years in the National Trauma Databank were reviewed from 1996 to 2005. Age trends and injury patterns were assessed over time. Injury Severity Score (ISS), length of stay (LOS), intensive care unit (ICU) use, comorbidities, complications, mortality, injury patterns, helmet use, and alcohol use were compared for subjects 40 and older versus those younger than 40-years-old. There were 61,689 subjects included. Over the study period, the mean age increased from 33.9 to 39.1 years (P < 0.01), and the proportion of subjects 40 years of age or older increased from 27.9 to 48.3 per cent. ISS, LOS, ICU LOS, and mortality were higher in the 40 years of age or older group (P < or = 0.01). The rates of admission to the ICU (32.3 vs. 27.3%), pre-existing comorbidities (20 vs. 9.7%), and complications (7.6 vs. 5.5%) were all higher in the 40 years of age and older group (P < 0.01). The average age of the injured motorcyclist is increasing. Older riders' injuries appear more serious, and their hospital course is more likely to be challenged by comorbidities and complications contributing to poorer outcomes. Motorcycle safety education and training initiatives should be expanded to specifically target older motorcyclists. PMID- 20349658 TI - Does a surgeon as first assistant reduce the incidence of common bile duct injuries during laparoscopic cholecystectomy? AB - This retrospective review supports the hypothesis that a surgeon acting as first assistant during laparoscopic cholecystectomy will reduce the incidence of significant common bile duct (CBD) injuries (BDIs). Central Carolina Surgery, P.A., is a single-specialty general surgery group of 19 surgeons that have performed 8767 laparoscopic cholecystectomies from October 1999 to December 2007. In those cases, 89 per cent of the cases had surgeons as first assistants and 66 per cent of the cases were performed with intraoperative cholangiography. Five cases of BDI occurred during this period for an incidence of 0.0570 per cent. Only three of these injuries required bilioenteric anastomotic reconstruction. When this same group of surgeons learned to perform laparoscopic cholecystectomy in 1990, their published series (Surgical Endoscopy: [1993] 7: 300 to 303] of 762 cases had 98 per cent of cases performed with a surgeon as first assistant and no CBD injuries. Only 27 per cent of those 762 cases had intraoperative cholangiograms. This single-practice general surgery experience supports the use of a surgeon as first assistant to lower the incidence of CBD injures. PMID- 20349659 TI - Management of breast abscesses in nonlactating women. AB - Breast abscess in nonlactating women is a rare clinic-pathological entity. A retrospective analysis of all cases of breast abscesses in nonlactating women in a community teaching hospital from 2000 to 2006 was performed. We analyzed their clinical characteristics, prevalence of diabetes mellitus (DM), surgical and medical management, and clinical outcome. We identified 116 breast abscesses in 98 nonlactating women; 89 per cent of patients were black. At presentation, 63 patients (64%) had a known history of DM and eight patients (8%) had newly diagnosed DM. Patients with DM had an increased length of hospital stay than nondiabetic women (P < 0.01). Most patients (70%) were treated with incision and drainage and antibiotics with a mean time of abscess resolution of 47 +/- 54 days. There was no correlation with breast abscess and smoking history. Glycemic control was suboptimal with 46 per cent of subjects receiving insulin therapy during the hospital stay. We found a high prevalence of DM (72%) in nonlactating women presenting with breast abscess. Diabetic women had a longer hospital stay and longer duration of the abscess compared with the patients without diabetes. Diabetes screening in nonlactating women with breast abscess and intensified glycemic control might improve clinical outcome. PMID- 20349660 TI - Hematocrit, systolic blood pressure and heart rate are not accurate predictors for surgery to control hemorrhage in injured patients. AB - Hematocrit (Hct), systolic blood pressure (SBP), and heart rate (HR) are considered to closely correlate with hypovolemia in injured patients. The clinical importance of these parameters in the early recognition of occult but clinically significant hemorrhage remains to be demonstrated. We undertook this study to assess the clinical importance of these parameters in the early recognition of occult hemorrhage in injured patients. A retrospective study of 7880 patients admitted to a Level I trauma center was carried out. Patients who underwent surgery were divided into the hemorrhage (n = 160) and no-hemorrhage group (n = 228). Hematocrit, SBP, and HR were correlated and receiver operating characteristic (ROC) curves were plotted. The ROC curves for Hct, SBP, and HR showed suboptimal areas under the graph. Even for different Hct thresholds and for hypotension and tachycardia, low predictive values were found. Although Hct, SBP, and HR levels were significantly altered among patients who require surgery for hemorrhage, the low predictive values of each parameter renders them as clinically unreliable individual tools for recognition of hemorrhagic patients who need surgery. Although useful in aggregate, as a pattern, or as indications for further diagnostic studies, these common parameters have limited usefulness individually. PMID- 20349661 TI - Malignant phylloides tumor in pregnancy. AB - Malignant phylloides tumors are exceedingly rare with few cases being reported in pregnancy. We describe the first case ever reported of a malignant phylloides tumor presenting in the first trimester of pregnancy and provide insight into the complexities of management as well as a review of the known literature. An extensive PubMed literature search for "cystosarcoma," "phylloides," and "pregnancy" was performed. References of each citation were reviewed. Only six previous cases of phylloides tumor in pregnancy were found, none of which were in the first trimester. Medical records of a patient presenting to our institution at 9 weeks gestation with a malignant phylloides tumor were reviewed. We further provide a review of the current literature of the management of phylloides tumor in pregnancy. A 27-year-old white G2P0SA1 woman with no family history of breast cancer presented with a right breast mass at her first prenatal examination at 9 weeks of pregnancy. Ultrasound confirmed a solid mass measuring 24 mm. Core needle biopsy demonstrated a malignant phylloides tumor. She previously had a fibroadenoma removed from the same breast 7 years previously. The current tumor was excised to clear margins. Histopathological examination revealed a 4-cm fibroepithelial tumor with marked stromal cellularity and a high mitotic count (five to seven mitoses/high-power field), confirming the diagnosis of malignant phylloides tumor. The patient continued her pregnancy without complications. Six other cases of phylloides tumor presenting in pregnancy have been reported in the literature, one of which had bilateral disease. Of these, the average patient age was 32 years (range, 28 to 35 years). The majority of these patients presented in their third trimester (mean, 29 weeks; range, 20 to 36 weeks) and often had large tumors (mean, 15 cm; range, 5 to 21 cm). Four of the seven tumors (57%) required a mastectomy. Previous cases have shown phylloides tumors to present in the third trimester as large masses that require mastectomy. With early detection, malignant phylloides tumors can present in the first trimester of pregnancy at smaller sizes; in these patients, breast-conserving surgery is possible. PMID- 20349662 TI - Are papillary microcarcinomas of the thyroid gland revealed by cervical adenopathy more aggressive? AB - Therapeutic attitudes for papillary thyroid microcarcinoma (PTMC) range from observation alone to aggressive management. Clinicopathologic features, therapeutic options, and follow-up results are described in a series of PTMC revealed by cervical adenopathies. Twelve patients were enrolled in this retrospective study. They were all treated by total/near-total thyroidectomy with dissection of suspect cervical lymph nodes followed by radioactive iodine (RAI) and suppressive L-thyroxine therapies. Mean age at diagnosis was 32 years with a mean elapsed time to diagnosis of 45.3 months. Fine needle aspiration cytology and excisional biopsy of the lymph node led to a diagnosis in all cases. Cervical mass was ipsilateral to primary tumor in six patients (50%). Multifocality, bilaterality, and capsular invasion were encountered in 66.7, 66.7, and 41.7 per cent of patients, respectively. Lymph node involvement was bilateral in seven patients (58.3%) of whom thyroid foci were unilateral in two. No complications of thyroidectomy were encountered. At 60-month-follow up, no recurrence or metastasis was noted. PTMC revealed by cervical lymph node metastasis shows aggressive clinicopathologic features. They must be considered as papillary thyroid cancers and managed by total/near-total thyroidectomy with bilateral lymph node exploration followed by RAI therapy and suppressive L-thyroxine doses. PMID- 20349663 TI - Linea alba fasciotomy: a novel alternative in trauma patients with secondary abdominal compartment syndrome. AB - Polytrauma patients needing aggressive resuscitation can develop intra-abdominal hypertension (IAH) with subsequent secondary abdominal compartment syndrome (SACS). After patients fail medical therapy, decompressive laparotomy is the surgical last resort. In patients with severe pancreatitis SACS, the use of linea alba fasciotomy (LAF) is an effective intervention to lower IAH without the morbidity of laparotomy. A pilot study of LAF was designed to evaluate its benefit in patients with SACS polytrauma. We conducted an observational study of blunt injury polytrauma patients undergoing LAF. Variables measured before and after LAF included intra-abdominal pressure (IAP, mmHg), abdominal perfusion pressure (APP, mmHg), right ventricular end diastolic volume index (RVEDVI, mL/m2), and ejection fraction. Of the five trauma patients with SACS, the mean age was 36 +/- 17, four (80%) male with an Injury Severity Score of 27 +/- 9. Pre and post-LAF, IAP was 20.6 +/- 4.7 and 10.6 +/- 2.7 (P < 0.0001), APP 55.2 +/- 5.5 and 77.6 +/- 7.1 (P < 0.0001), RVEDVI 86.4 +/- 9.3 and 123.6 +/- 11.9 (P < 0.0001), and EF 27.6 +/- 4.2 and 40.8 +/- 5 (P < 0.0001), respectively. One patient needed full decompression for bile ascites from unrecognized liver injury. Linea alba fasciotomy, as a first-line intervention before committing to full abdominal decompression in patients with SACS trauma, improved physiological variables without mortality. Consideration for LAF as a bridge before full abdominal decompression needs further evaluation in patients with polytrauma SACS. PMID- 20349664 TI - Evaluation of a new hemostatic agent in a porcine grade V liver injury model. AB - Our objective was to evaluate the hemostatic efficacy of a newly modified chitosan in a porcine grade V liver injury model. Fifteen Yorkshire pigs underwent standardized grade V liver injuries with a specially designed liver clamp and were randomized to either modified chitosan (MC) patch treatment or standard gauze packing. Free bleeding was allowed for 30 seconds. Fluid resuscitation was infused as necessary to reestablish a mean arterial pressure (MAP) within at least 80 per cent of the preinjury MAP. Animals were observed for 90 minutes or until death. Endpoints were survival, total blood loss, time to hemostasis, and resuscitation MAP, and resuscitation volume. Total mean blood loss was less in the MC patch group (464 +/- 267 mL vs 1234 +/- 78 mL, P < 0.001). Time to hemostasis was significantly less (4.8 +/- 2.5 minutes in the MC patch group vs 9.6 +/- 2.5 minutes, P < 0.01). Fluid resuscitation was less (1098 +/- 459 mL in the MC patch group vs 1770 +/- 172 mL, P < 0.01). Survival was 100 per cent in the MC patch group and 80 per cent in the gauze packing group. MC patches demonstrate the continued hemostatic agent evolution for improved control of lethal solid organ bleeding. PMID- 20349665 TI - Laparoscopic duodenojejunostomy for superior mesenteric artery syndrome. AB - Superior mesenteric artery (SMA) syndrome is an uncommon condition of duodenal obstruction secondary to extrinsic vascular compression. With the advent of laparoscopy, an emerging option to treat SMA syndrome is laparoscopic duodenojejunostomy. Given the rarity of the condition a critical appraisal of the effectiveness and safety of this relatively new surgical option has not been performed. Here we present a case report and a critical review of all published reports of laparoscopic duodenojejunostomy. A systematic literature review of all published reports describing laparoscopic duodenojejunostomy was performed by querying the MEDLINE database using keywords: laparoscopic duodenojejunostomy and SMA syndrome. Nine articles were reviewed which were mainly case reports and case series (level 5 data), reporting on a total of 13 patients, with 32 per cent of the patients being male and 68 per cent female. The diagnosis was established preoperatively in 62 per cent of the cases, the length of stay was 4.5 days, the morbidity rate was 7 per cent, and no mortalities were reported. The operation was considered successful in 100 per cent of patients. Laparoscopic duodenojejunostomy seems to be a safe and effective treatment for patients with SMA syndrome, but more data is required to recommend this operative option as the standard of care. PMID- 20349666 TI - Post-operative nausea and vomiting (PONV) after thyroid surgery: a prospective, randomized study comparing totally intravenous versus inhalational anesthetics. AB - The incidence of postoperative nausea and vomiting (PONV) after thyroidectomy and the association of Propofol versus Sevoflurane use for anesthesia maintenance were investigated during a randomized, prospective study. One hundred and ninety eight patients underwent thyroidectomy receiving either Sevoflurane (0.5-1.3% end tidal) or Propofol (50-200 mg/kg/min) for anesthesia maintenance. All patients received Propofol for induction of anesthesia, Succinylcholine or Vecuronium, Nitrous Oxide, and Fentanyl. Prophylactic antiemetics were not administered. The combined incidence of PONV was 54.4 per cent over the 24-hour postoperative evaluation period. PONV was more common in patients receiving Sevoflurane than Propofol for maintenance of anesthesia (64.6% vs 43.8%). In women (n = 117), the incidence of PONV resulted higher when receiving inhalational Sevoflurane than Propofol for maintenance (70.6% vs 42.4%). However, in men (n = 81), there was no significant difference in PONV between anesthetic regimens (47.4% with Sevoflurane vs 49.6% with Propofol). Patients undergoing thyroid surgery are at high risk for the development of PONV. Propofol for maintenance of anesthesia, although more expensive than Sevoflurane, may reduce the rate of PONV. PMID- 20349667 TI - Blood and organ donation patterns of trauma surgeons. AB - Allogenic blood product transfusion and organ donation are critical components of modern medicine. However, only 5 per cent of the eligible population donate blood and only 53 per cent declare themselves organ donors. Trauma surgeons have an intimate exposure to these needs and their personal donation patterns may reflect this knowledge. A 14 question survey about personal blood and organ donation was sent to 635 members of the American Association for the Surgery of Trauma by e mail. Seventy-eight per cent of respondents have donated blood and 86 per cent of those donors have done so repeatedly. However, 83 per cent of respondents have not given blood in the past year. Medical reasons were the most common reason cited for inability to donate (45%). With regard to organ donation, 90 per cent of respondents have filled out the organ donation section on their driver's license and 89 per cent have discussed organ donation with their family. The rates of blood and organ donation are higher than the rates of the general population. Trauma surgeons are likely to be blood and organ donors. Their intimate knowledge of the importance of donation plays a role. Personal medical conditions that restrict donation were, among respondents, a more common cause of failure to donate than were time constraints. PMID- 20349668 TI - Factors associated with re-excision in patients with early-stage breast cancer treated with breast conservation therapy. AB - One of the risks of breast conservation surgery is local recurrence, which predominantly occurs as a result of inadequate surgical margins. The purpose of this study was to identify factors associated with close or positive surgical margins leading to reexcision (RE). The charts of 532 consecutive breast cancer patients treated at our center between September 2001 and June 2007 were reviewed to evaluate patients who opted for breast conservation surgery and needed reexcision. A total of 351 patients were treated with breast conservation, of which 118 (34%) had positive or close surgical margins and went on to RE. On univariate analysis, factors that significantly correlated with RE (P < 0.05) were preoperative diagnosis, final pathology, size of tumor, and presentation with nipple discharge. RE was necessary in 53 per cent of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS), 57 per cent of patients diagnosed by surgical excision, 86 per cent of patients presenting with nipple discharge, and 87 per cent of patients with DCIS or invasive carcinoma with extensive intraductal component in the final pathology. Additionally, 53 per cent of patients with T3 tumors required RE. Age, race, and grade of tumor had no effect on RE rates. Most (75%) patients were able to ultimately have breast conservation. PMID- 20349669 TI - Hepatocellular carcinoma arising within focal nodular hyperplasia. PMID- 20349670 TI - A rare case of a 1.5 mm papillary microcarcinoma of the thyroid presenting with pituitary metastasis. PMID- 20349671 TI - Endovascular exclusion of ruptured popliteal artery aneurysm. PMID- 20349672 TI - The sign of Leser-Trelat in colorectal adenocarcinoma. PMID- 20349673 TI - Ruptured cystadenoma of a duplicated appendix. PMID- 20349674 TI - Internal carotid artery thrombosis after blunt trauma--salvage therapy with the penumbra thrombectomy system. PMID- 20349675 TI - Rett Syndrome and gastric perforation: total or partial gastrectomy in an emergency situation? PMID- 20349676 TI - A stercoral sigmoid ulcer masquerading as perforated diverticulitis. PMID- 20349677 TI - Indoor tanning: just say no. PMID- 20349678 TI - What is your diagnosis? Metastatic adenocarcinoma. PMID- 20349679 TI - Impetigo update: new challenges in the era of methicillin resistance. AB - Impetigo is a bacterial infection of the superficial epidermis most commonly seen in infants and children. It is clinically characterized by crusted erosions or ulcers that may arise as a primary infection in which bacterial invasion occurs through minor breaks in the cutaneous surface or a secondary infection of a preexisting dermatosis or infestation. Impetigo occurs in 2 forms: bullous and nonbullous. Staphylococcus aureus currently is the most common overall cause of impetigo, but Streptococcus pyogenes remains an important cause in developing nations. Community-acquired methicillin-resistant S aureus (CA-MRSA) poses a challenge because of its enhanced virulence and increasing prevalence in children. For limited uncomplicated impetigo, either topical mupirocin or fusidic acid is as effective if not more effective than systemic antibiotics. For extensive or complicated impetigo, systemic antibiotics may be warranted, but beta-lactam antibiotics should be avoided if methicillin-resistant S aureus (MRSA) is suspected. PMID- 20349680 TI - Lymphocutaneous nocardiosis: a case report and review of the literature. AB - Nocardiosis remains a fairly uncommon disease in the United States. Cutaneous nocardiosis is one of many infections that can spread in a sporotrichoid pattern and therefore can be difficult to diagnose without a high index of suspicion. It is mainly caused by Nocardia asteroides and Nocardia brasiliensis, with N brasiliensis isolated in most cases of lymphocutaneous nocardiosis. We present a case of lymphocutaneous nocardiosis in a 65-year-old immunosuppressed man and review the literature. PMID- 20349681 TI - Notalgia paresthetica associated with cervical spinal stenosis and cervicothoracic disk disease at C4 through C7. AB - Notalgia paresthetica (NP) is a common refractory, sensory, neuropathic syndrome with the hallmark symptom of localized pruritus of the unilateral infrascapular back. It generally is a chronic noncurable condition with periodic remissions and exacerbations. While the dermatologic syndrome may be multifactorial in etiology, a possible association with underlying cervical spine disease should be evaluated for proper treatment. Collaborative multispecialty evaluation by dermatology, radiology, orthopedic surgery, and neurology may be indicated for primary management of this condition. First-line therapy for NP with associated cervical disease may include nondermatologic noninvasive treatments such as spinal manipulation, physical therapy, massage, cervical traction, cervical muscle strengthening, and oral nonsteroidal anti-inflammatory drugs and muscle relaxants. Notalgia paresthetica may in fact be a cutaneous sign of an underlying degenerative cervical spine disease. We report a case of a patient with cervical spinal stenosis that corresponded directly with the clinical findings of NP. PMID- 20349682 TI - The role of a dermatologist on military humanitarian missions. AB - The US military in conjunction with allied military services and nongovernmental organizations have embarked on various humanitarian missions to underserved areas worldwide. These missions illustrate what interoperability between nations can accomplish. Dermatologists involved with humanitarian missions encounter many conditions rarely seen in developed countries and learn to practice general dermatology with limited resources in austere environments. PMID- 20349683 TI - Gastric carcinoma of the umbilicus: case report of Sister Mary Joseph nodule. AB - Sister Mary Joseph nodule is a metastatic lesion of the umbilicus, which is an uncommon phenomenon that carries an ominous prognosis. We describe a patient with gastric cancer who presented with asymptomatic papules on the umbilicus proven to be metastatic foci by biopsy. The lesion represented spread of the malignancy despite chemotherapy; thus, treatment was initiated with second-line agents. Sister Mary Joseph nodule can be the first presenting sign of an occult malignancy, or as demonstrated in this case, a sign of disease progression. Given the variable appearance of the lesions, a high index of suspicion is necessary to make an accurate diagnosis. PMID- 20349684 TI - Effective and safe combination therapy for severe acne vulgaris: a randomized, vehicle-controlled, double-blind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel with doxycycline hyclate 100 mg. AB - There is a paucity of treatment options for severe acne vulgaris aside from oral isotretinoin. This randomized, vehicle-controlled, multicenter, double-blind study evaluated the efficacy and safety of combination therapy using adapalene 0.1%-benzoyl peroxide 2.5% (A/BPO) fixed-dose combination gel with doxycycline hyclate 100 mg in the treatment of severe acne vulgaris. A total of 459 participants were randomized in a 1:1 ratio to receive oral doxycycline hyclate 100 mg once daily and either A/BPO or vehicle once daily for 12 weeks. Efficacy in the A/BPO with doxycycline group was demonstrated as early as week 2 compared with the vehicle arm for total, inflammatory, and noninflammatory lesions (all P < .005). At week 12, this combination was superior to vehicle with doxycycline in reducing total, inflammatory, and noninflammatory lesion counts (an added incremental benefit of 23%, 24%, and 21%, respectively), as well as for global success and overall participant satisfaction (all P < .001). Digital UV fluorescence photography demonstrated a rapid reduction in Propionibacterium acnes in the A/BPO with doxycycline group, particularly within the first 4 weeks. These findings provide evidence on the efficacy of combining A/BPO and the oral antibiotic doxycycline in the treatment of severe acne vulgaris. PMID- 20349686 TI - Homicide and allied inquiries: in whose best interests? AB - Over a decade ago the present author presented some comments on homicide inquiries in this journal. Since then there have been a number of important developments, including the increase in the number of such inquiries and changes in their constitution and functions. A somewhat neglected area has been soliciting the views of those who chair such inquiries. The present contribution endeavours to remedy this deficiency. PMID- 20349685 TI - Safety and efficacy of sertaconazole nitrate cream 2% in the treatment of tinea pedis interdigitalis: a subgroup analysis. AB - Sertaconazole nitrate is a broad-spectrum antifungal agent indicated in the United States for the treatment of tinea pedis interdigitalis. The objective of this subgroup analysis was to evaluate the safety and efficacy of sertaconazole nitrate cream 2%, specifically in participants with tinea pedis interdigitalis (ie, fungal skin disease of the toe web) of dermatophyte origin. A total of 92 participants were included in this analysis. The primary end points were eradication of the pathogen (confirmed by fungal culture results) and reduction in total clinical score (TCS) of at least 2 points. Secondary end points included reducing signs and symptoms and reporting adverse events (AEs). After 4 weeks of treatment, 88.8% (79/89) of evaluable participants achieved success on the primary end points. Most participants also demonstrated substantial improvement in signs and symptoms after 4 weeks of treatment: 63.7% (58/91) were free of erythema, 33.0% (30/91) were free of desquamation, and 91.2% (83/91) were free of itch. The rate of reported AEs was low (8.7% [8/92]), and none were considered serious. These findings indicate that sertaconazole nitrate cream 2% is highly safe and effective in the treatment of tinea pedis interdigitalis. PMID- 20349687 TI - Bath-related deaths in Kagoshima, the southwest part of Japan. AB - In Japan, sudden death in the bathroom (what we call 'bath-related death') has been reported to occur particularly in the elderly population in the winter. This investigation aimed to obtain a better understanding of the factors associated with bath-related deaths. For this purpose, a retrospective review of the inquest records in Kagoshima Prefecture, the southwest part of Japan, during 2006-2007 was performed. There were 338 cases of bath-related death, which corresponds to a crude mortality rate of 9.7 per 100,000 persons per year. The occurrence of bath related death was similar to that of other prefectures in Japan, despite the warm environment in Kagoshima. The victims' ages ranged from 37 to 101 years (mean 76.6 years) and 88.8% of patients were over 65 years. The associated factors included winter season (56.2%) and a medical history of hypertension (37.3%). These demographic and circumstantial factors correlated with previous studies in Japan. These results suggest that the Japanese method of bathing, in addition to cold bathrooms in winter, contributes to the high rate of bath-related death in Japan. In addition, the mortality rate of people who lived alone was significantly higher than that of those who lived with their families. Most cases occurred in the home bathroom (84.9%) at the time when elderly people usually bathe (48.7%). Our results indicate that bath-related death occurs most often during the normal daily life of the aged. Protective activities of the Japanese government and society should aim to reduce the number of these tragic deaths in the bathroom. Further, no autopsies were performed on the cases in this study. Therefore, the rate of autopsies in bath-related death should be increased in order to accumulate data based on objective evidence. PMID- 20349688 TI - Demographic and referral patterns of people detained under Section 136 of the Mental Health Act (1983) in a south London Mental Health Trust from 2005 to 2008. AB - This study aimed to retrospectively examine demographic and referral data for all detainees under Section 136 of the Mental Health Act (1983) at a 'place of safety' in one London Mental Health Trust over a three-year period. Data were collected for 887 consecutive detentions and indicated a clear over representation of black detainees compared with their representation in the local population. A high proportion of detentions (41.2%) did not result in hospital admission. Implications for practice and service user experience should be considered as long as Section 136 remains an entry point to mental health services for many black people. There are implications for interprofessional practice where Mental Health Trust resources are expended supporting Section 136 detentions in which no hospital treatment follows. PMID- 20349689 TI - A comparison of suicide and undetermined deaths in Cornwall across national and local agencies. AB - We looked to evaluate the reporting pathways and statistics between relevant stakeholders for reporting suicides and undetermined deaths in Cornwall. We checked on the correlation of the numbers provided for suicides and open verdicts given by different national and regional agencies including the local Coroner's office, Office of National Statistics (ONS), Cornwall Partnership NHS Trust (CPT) and The National Confidential Inquiry (NCI) into suicides for Cornwall. We examined the data of suicides and open verdicts presented by these agencies between the years 2000 and 2002. Our study shows that the data transfer between the relevant agencies (local Coroner, ONS, CPT and NCI) can be inaccurate. These inaccuracies not only prevent establishment of clear records but could also impact on policy decisions. It is also important to recognize that NHS trusts involved in mental health are being evaluated on their record on suicide prevention which in some senses is the most important outcome measure, thus making it important for inspecting bodies to look out for and take account of different figures from different agencies. PMID- 20349690 TI - Fatal accidental fall from height in infants and children: a study from South Delhi. AB - One hundred and seventy-four deaths of infants and children due to accidental fall from height received from South Delhi for autopsy were studied during the 10 year period from January 1998 to December 2007 at the All India Institute of Medical Sciences, New Delhi. Data were analysed with regard to age, sex, location of fall, height of fall, pattern of injury, cause of death and seasonal variation. These cases represented approximately 22.56% of all deaths due to a fall from height and 1.31% of all medicolegal autopsies conducted during the period. There were 106 male (60.9%) and 68 female (39.1%) victims. Age-specific rate of fall showed that the highest rate was in toddlers (39.65%), followed by 26.43% each in preschool children and school-going children and the least in infants (7.47%). The head and face was the most frequently injured body region (93.67%) and the skull was the commonest bone fractured (59.19%). The most common cause of death was head injury (84.48%). Major fall sites in decreasing order of frequency were rooftop (38.50%), balcony (24.13%), household furniture (21.26%), staircase (6.89%), window (4.59%), wall (1.72%), rickshaw/bicycle (1.15%) and tree (0.57%). Most fatalities due to a fall from height were reported in the rainy season. PMID- 20349691 TI - Study of suicides reported to the Coroner in Colombo, Sri Lanka. AB - INTRODUCTION: Deaths from suicide reached a peak in Sri Lanka in 1995. Several interventions reduced the suicide rate of 48.7 per 100,000 in 1995 to 23 per 100,000 in 2006, though it is still a major socioeconomic problem. All suicides have to be reported to the Inquirer of Sudden Death (ISD) or 'Coroner', according to the Criminal Procedure Code. METHOD: All deaths where a verdict of 'suicide' was given after an inquest at the Coroner's Court, Colombo, in 2006 were studied. Close relations or friends who attended the inquest were interviewed by medically qualified research assistants. Age, sex, marital and occupational status, level of education, living circumstances and method and reasons for the suicide were studied. RESULTS: During 2006, 151 deaths from suicide were documented, of which 93 (62%) were men. The majority (47%) were aged between 20 and 29 years. One third of the victims was unemployed. At the time of committing suicide, 75% were living with family; 89 (59%) were married and 46 (31%) were single. Poisoning was the cause of death in 66 (44%), 48 (70%) of which were due to pesticides. Burns caused 51 (34%) deaths. Other common causes of death included hanging (11%), jumping in front of a train (7%) and drowning (3%). The commonest reason for suicide was dispute with the spouse/marital disharmony (30%). Other reasons were dispute with parents (8%), financial matters (7%), organic diseases (7%), alcoholism (7%), psychiatric illnesses (6%) and disputes in love affairs (5%). In 29 cases (19%), no definite reason for the suicide was evident. DISCUSSION: Self poisoning and self-immolation were the commonest methods used to commit suicide. Marital disharmony was the main reason (30%). Psychiatric illnesses were responsible for only 6%. Future interventional activities should include secure access and restriction of the availability of pesticides and drugs, empowering people to manage anger and conflicts, and recognition and treatment of alcoholism and psychiatric illnesses. The success story of the reduction in the incidence of suicides in Sri Lanka should be a lesson to many developing countries where suicide is a major socioeconomic and health issue. PMID- 20349692 TI - The use of Section 136 (Mental Health Act 1983) in Gloucestershire. AB - The small number of published studies on the use of Section 136 (S136) of the Mental Health Act 1983 may reflect neither the current situation nor the true national picture as most of the research comes from large urban centres and was published before 1997. We studied the use of S136 between 2002 and 2006 in Gloucestershire, a rural English county with a population of approximately 585,000, by analysing data held by the police and local mental health services. On average 192 subjects (range 176-203) were detained each year under S136, equating to a population rate of 32.8 S136 detentions per 100,000 per year in Gloucestershire. In contrast to other published studies, ethnic minorities, particularly Afro-Caribbean males, were overrepresented only in a minor way. Of those individuals detained, about a third were admitted, a lower rate than in other studies. Acts or threats of self-harm were common (55%), but acts or threats of violence (28%) and evidence of intoxication (16%) were present in a minority, suggesting that detainees are more likely to pose a risk to themselves than others. PMID- 20349693 TI - Section 136 of the Mental Health Act: a new literature review. AB - Section 136 of the Mental Health Act 1983 (amended) provides police officers in the United Kingdom with the authority to remove individuals who appear to be suffering from a mental illness from any public place to a designated 'place of safety' for appropriate assessment. A considerable amount of research has been dedicated to investigate who is detained under this section and how it is implemented. A review of the literature revealed a high prevalence of schizophrenia, personality disorders and mania in individuals detained under Section 136 and an over-representation of black detainees. Several studies also reported poor communication between different agencies and poor levels of knowledge regarding the implementation of the section. There is a lack of qualitative research exploring detainee and professional experience of Section 136 and in particular the patient pathway to mental health care via Section 136 experienced by black detainees. Implications for clinical practice, multi-agency collaboration and future research are discussed. PMID- 20349694 TI - Medicolegal issues arising when pacemaker and implantable cardioverter defibrillator devices are deactivated in terminally ill patients. AB - The number of patients receiving pacemakers and implantable cardioverter defibrillator (ICD) devices continues to increase dramatically. In this paper, the issue of when it is appropriate to deactivate these devices if the patient becomes terminally ill and the medicolegal implications of this action are examined. This appears to constitute a withdrawal of treatment. However, the issue has never come before the courts and therefore no medicolegal guidance exists on the point. This paper highlights a lack of knowledge among health-care staff regarding switching off electromechanical devices in terminally ill patients. We propose some guidance and recommendations for dealing with this issue when it arises in practice, and highlight some important differences between pacemakers and ICDs that will influence decision-making. Conclusions are expressed regarding how this issue should be dealt with in the postmortem setting and in the antemortem setting, where the issue of capacity and consent will influence decisions regarding deactivating these devices. PMID- 20349695 TI - Cadaver procurement for anatomy teaching: legislative challenges in a transition related environment. AB - BACKGROUND: Human gross anatomy is one of the cornerstones of a medical curriculum and cannot be performed without adequate cadaver procurement, which is a particular challenge for medical schools with a large student enrolment. The authors present the situation in a country with a low public awareness for willed body donor programmes and the prior absence of adequate legislation. AIM: Against this background, a comprehensive proposition of a whole-body procurement procedure was elaborated in the health-care law. RESOLVING THE PROBLEM: The main goals of the proposition were: (a) identification of options for cadaver procurement (body bequeathal programme, unclaimed bodies and body donated with the permission of the next-of-kin); (b) defining the chain of order and responsibility of institutions in informing the medical school of the possible candidate for body procurement; (c) body storage and related procedures; (e) confidentiality of the deceased's personal data; (f) burial procedure of the deceased's remains. CONCLUSIONS: The authors are convinced that the willed programme for whole-body donation is a definite aim of such a legislation. However, we suggest that the acquisition of unclaimed bodies is maintained as a temporary solution, until a satisfactory level of public awareness of the problem has been reached. PMID- 20349696 TI - Firearm deaths in Australia after law reform. PMID- 20349697 TI - Errors in autopsy of a patient with ventricular septal defect and tuberous sclerosis. PMID- 20349698 TI - Deployment and operation of a transportable burn intensive care unit in response to a burn multiple casualty incident. AB - In many hospitals, intensive care units (ICUs) operate at or above capacity on a daily basis. Multiple casualty incidents will create a sudden need for additional ICU beds and hospital planning for disaster response must anticipate the need for rapid ICU expansion. In this article, the authors describe the management of 6 patients who were burned in Guam and successfully transported a distance of 7,268 miles to San Antonio, TX, for tertiary burn center care. The mission required creation of a temporary burn ICU at Tripler Army Medical Center in Hawaii, approximately midway between the referring hospital and the receiving burn center. A method of creating a temporary burn center is described. Lessons learned, including the need to standardize equipment, and to cross-train and cross-credential medical personnel, are applicable to both military and civilian mass casualty management. PMID- 20349699 TI - Pandemic-related ability and willingness in home healthcare workers. AB - OBJECTIVE: To assess pandemic-related attitudes and behavioral intentions of home healthcare workers (HHCWs). DESIGN: Cross-sectional survey. SETTING: New York City. PARTICIPANTS: A convenience sample of 384 HHCWs. MAIN OUTCOME VARIABLES: Ability and willingness to report to work during a pandemic influenza outbreak. RESULTS: A large proportion of HHCWs reported that they would be either unable or unwilling (or both) to provide care to their current (83 percent) or new (91 percent) patients during a pandemic. Ability was significantly associated with not having children living at home, having alternatives to mass transportation, not having a spouse/partner employed as a first responder or healthcare worker, and having longer tenure (ie, six or more years) in homecare. During an outbreak, 43 percent of HHCWs said they would be willing to take care of current patients and only 27 percent were willing to take care of new patients. Willingness to care for both current and new patients was inversely associated with fear for personal safety (p < 0.01). Provision of key elements of a respiratory protection program was associated with decreased fear (p < 0.05). Most participants (86 percent) had not received any work-based, pandemic-related training, and only 5 percent reported that their employer had an influenza pandemic plan. CONCLUSIONS: Given that a large majority of the participating HHCWs would either be unable or unwilling to report to duty during a pandemic, potential shortfalls in this workforce may occur. To counter this, organizations should focus on strategies targeting intervenable barriers to ability and to willingness (ie, the provision of a vaccine and respiratory protection programs). PMID- 20349700 TI - Pediatric disaster preparedness of a hospital network in a large metropolitan region. AB - OBJECTIVES: We describe pediatric-related emergency experiences and responses, disaster preparation and planning, emergency plan execution and evaluation, and hospital pediatric capabilities and vulnerabilities among a disaster response network in a large urban county in the West Coast of the United States. METHODS: Using semistructured key informant interviews, the authors conducted qualitative research between March and April 2008. Eleven hospitals and a representative from the community clinic association agreed to participate (86 percent response rate) and a total of 22 key informant interviews were completed. Data were analyzed using ATLAS.ti.v.5.0, a qualitative analytical software program. RESULTS: Although hospitals have infrastructure to respond in the event of a large-scale disaster, well-established disaster preparedness plans have not fully accounted for the needs of children. The general hospitals do not anticipate a surge of pediatric victims in the event of a disaster, and they expect that children will be transported to a children's hospital as their conditions become stable. CONCLUSIONS: Even hospitals with well-established disaster preparedness plans have not fully accounted for the needs of children during a disaster. Improved communication between disaster network hospitals is necessary as incorrect information still persists. PMID- 20349701 TI - Quality control in disaster medicine training--initial regional medical command and control as an example. AB - OBJECTIVE: The aim of this study was to show the possibility to identify what decisions in the initial regional medical command and control (IRMCC) that have to be improved. DESIGN: This was a prospective, observational study conducted during nine similar educational programs for regional and hospital medical command and control in major incidents and disasters. Eighteen management groups were evaluated during 18 standardized simulation exercises. MAIN OUTCOME MEASURE: More detailed and quantitative evaluation methods for systematic evaluation within disaster medicine have been asked for. The hypothesis was that measurable performance indicators can create comparable results and identify weak and strong areas of performance in disaster management education and training. METHODS: Evaluation of each exercise was made with a set of 11 measurable performance indicators for IRMCC. The results of each indicator were scored 0, 1, or 2 according to the performance of each management group. RESULTS: The average of the total score for IRMCC was 14.05 of 22. The two best scored performance indicators, No 1 "declaring major incident" and No 2 "deciding on level of preparedness for staff" differed significantly from the two lowest scoring performance indicators, No 7 "first information to media" and No 8 "formulate general guidelines for response." CONCLUSION: The study demonstrated that decisions such as "formulating guidelines for response and "first information to media" were areas in initial medical command and control that need to be improved. This method can serve as a quality control tool in disaster management education programs. PMID- 20349702 TI - Experiences of Iraqi doctors in Jordan during conflict and factors associated with migration. AB - OBJECTIVES: To document the experiences of Iraqi doctors residing in Jordan before departure from Iraq and to assess factors associated with migration. METHODS: Respondent-driven sampling was used to obtain information from 401 Iraqi doctors arriving in Jordan after the invasion of 2003. Three seeds were used and chains were carried out to 10-11 waves of respondents; interviews were carried out either in person or by mobile phone. RESULTS: Migration of Iraqi doctors to Jordan peaked in 2006; 94 percent of doctors were from Baghdad and 25 percent had been internally displaced before migration to Jordan. Departure from Iraq was associated with a violent event in 61 percent (confidence interval [CI]: 56-65) of cases and 75 percent (CI: 70-79) of doctor households experienced a violent event before migration. Kidnappings or assassination attempts were reported by 17 percent (CI: 25-34) of doctors; male sex and older age were significantly associated with increased risk in multivariate models. Only 30 percent (CI: 25 34) of doctors reported they have plan to return to Iraq when the conflict is over and 6 percent (CI: 4-9) reported planning to return to Iraq within a year; the majority (52 percent, CI: 47-57) planned to settle in a third country. CONCLUSIONS: Iraq has lost many of its doctors as a result of the conflict, and the majority of those displaced in Jordan have no plans to return. The human capital losses associated with the large-scale displacement of Iraqi doctors are substantial and have left a critical void in human capital that will likely impact the health system for decades. PMID- 20349703 TI - Response capabilities of the National Guard: a focus on domestic disaster medical response. AB - The National Guard has a 373-year history of responding to the nation's call to duty for service both at home and abroad (The National Guard Bureau Web site: Available at http://www.ngb.army.mil/default. aspx.). The National Guard (NG) is a constitutionally unique organization (United States Constitution, US Government Printing Office Web site: Available at http://www.gpoaccess.gov/constitution/index.html.). Today's Guard conducts domestic disaster response and civilian assistance missions on a daily basis. Yet, the NG's role, mission, and capabilities are not well-known or understood. The National Response Framework (NRF) places significant responsibility on the local and state disaster planners (Department of Homeland Security: National Response Framework. US Department of Homeland Security, Washington, DC, January 2008). The public health professionals are an integral component of the disaster planning community. It is critical that the public health community be knowledgeable of types and capabilities of all the response assets at their disposal. PMID- 20349704 TI - Hurricane Katrina and the need for changes in the federal funding of disaster mental health. AB - Recent findings showing chronic post-traumatic stress disorder and other mental health symptoms in individuals exposed to Hurricane Katrina cogently argues for changes in the federal funding of mental health following disasters. This commentary discusses the evidence for protracted high rates of mental health problems in both adults and children following Katrina. The limitations to current mental health funding legislation post-disaster are noted, and initial suggestions for additional disaster-related mental health funding programs are made. PMID- 20349705 TI - Mass gathering medical care: to calculate the Medical Usage Rate of Galway Races. AB - Medical Usage Rate (MUR) of Galway Races: The Galway Races is the most popular horse-racing festival in Ireland. It takes place for a week starting from the last Monday in July. The races are held at Ballybrit race course in Galway. During the 7 days of racing, about 180,000 people attend. The average temperature in Galway around that time of the year is around 15-200C. The aim of this study is to calculate the MUR of Galway Races and to develop a model to predict the MUR for Galway Races in future. The MUR of Galway Races is calculated by looking retrospectively at the medical records of the last 11 years of Galway Races from 1997 to 2007. The Galway Races has a MUR of 3.67 patient per ten thousand. Based on the figures for last 10 years, the predictive MUR for Galway Races 2008 calculated before the races and actual figures in 2008 races is comparable. PMID- 20349706 TI - [Systems biology applications to explore secondary metabolites in medicinal plants]. AB - Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically. PMID- 20349707 TI - [Effects of culture conditions on biomass and active components of adventitious roots culture in Panax ginseng]. AB - OBJECTIVE: To optimize the culture condition of adventitious roots of Panax ginseng. METHOD: The adventitious roots were obtained through tissue culture by manipulation of inoculum, various sucrose concentrations and salt strength. The contents of ginsenosides Re, Rb1 and Rg1 were determined by HPLC while the contents of polysaccharides were determined by ultraviolet spectrophotometry. RESULT: The multiplication of adventitious roots reached the peak when the inoculum was 20 g x L(-1). The effects of sucrose concentration and salt strength on adventitious roots were observed. The contents of polysaccharides were higher when the medium contained more sucrose. 40 g x L(-1) sucrose was favorable for roots growth and biosynthesis of Re, while 30 g x L(-1) was favorable for the biosynthesis of Rb1 and Rg1. 3/4MS medium was benefit for the growth of adventitious roots and the biosynthesis of ginsenosides. The contents of polysaccharides were decreased with the increase of salt strength. CONCLUSION: The results showed that inoculum, various sucrose concentrations and salt strength have significant influences on adventitious roots growth, secondary metabolite and polysaccharide synthesis in P. ginseng. PMID- 20349708 TI - [Phylogenetic analyses of some important Paris species based on sequences of matK gene]. AB - The matK genes of 10 samples in Paris from Hunan, Yunnan and Jilin provinces were sequenced and compared. The phylogenetic tree was constructed based on the matK gene sequences and the ten pairs samples were divided into four groups. The results did not support the reality of four taxa named P. polyphylla var. pseudothibetica, P. polyphylla var. yunnanensis, P. polyphylla var. appendiculata and P. polyphylla var. chinenis. They are supposed to be treated as different forms of P. polyphylla var. polyphylla. PMID- 20349709 TI - [Nutrient uptake characteristics of nitrogen, phosphorus and potassium of Pinellia ternate from Sichuan during growth stage]. AB - OBJECTIVE: To study the absorption characteristics of nitrogen (N) , phosphorus (P) , and potassium (K) of Pinellia ternate from Sichuan under the cultivated condition. METHOD: The samples of P. ternate S-29 and S-33 from Sichuan were regularly collected randomly, the contents of nitrogen, phosphorus and potassium of each part (aerial and underground parts) were determined, and their distribution and accumulation characters of nitrogen, phosphorus, potassium were also studied. RESULT: The absorption rate of aerial and underground parts of P. ternate were different in nitrogen, phosphorus, and potassium at different growing stages. Among them, the potassium uptake was the highest, while the phosphorus uptake was the lowest. Totally, the uptakes of nitrogen, phosphorus and potassium of P. ternate from Sichuan during "sprout tumble" stage were comparatively higher than that not at "sprout tumble" stage. A significant correlation was observed between the phosphorus and potassium uptake of the aerial and underground parts, respectively (P < 0.05). And there was also significant positive correlation between the nitrogen and phosphorus uptake at underground parts (P < 0.05). During the growth stage of P. ternate, for producing 100 kg air-dried P. ternate, 5.02-5.64 kg N, 2.44-2.56 kg P205, 11.62 13.49 kg K20 were needed to be absorbed. CONCLUSION: P. ternate from Sichuan should be given enough base fertilizer in field cultivation, and then be supplied with phosphorus and potassium by combining foliar spray with field application during the middle ten days of June and last ten days of August. The ratios of potassium should be properly improved. There was promoting effect in the phosphorus and nitrogen assimilations of the underground parts of P. ternate from Sichuan. PMID- 20349710 TI - [Floral dynamic and pollination habit of Fritillaria cirrhosa]. AB - OBJECTIVE: To find the sexual reproduction characteristics and improve the seed propagation and new variety breeding of Fritillaria cirrhosa. METHOD: Flower, anther and pistil development were observed. Pollinating in different development period and bagging were used to measure stigma maturity situation and natural outcrossing rate. RESULTS AND CONCLUSION: It took 12 days from floral bud emergency to finished flowering. It was observed that anther opened in longitudinal direction and pollen was ejected for 2-4 days continuously. Pistil matured earlier, and chapiter could be fertilized from middle bud stage the third day after flowering, but the most suitable time was 2-3 day after the corolla opening. The natural outcrossing rate was 81.9%. F. cirrhosa is a typical xenial plant. PMID- 20349711 TI - [Corneal penetration of PAMAM dendrimers-coated puerarin liposomes]. AB - OBJECTIVE: To study the corneal penetration of PAMAM dendrimers-coated puerarin liposomes in rabbits. METHOD: Evaluated PAMAM (G2, G3) dendrimers-coated puerarin liposomes were prepared and the in vitro transcorneal penetration were compared to puerarin drop solution and uncoated liposomes. The effect of different proportion of PAMAM to phospholipids in formulation on corneal penetration and the penetration parameters were investigated. RESULT: The steady state fluxes and permeability coefficients of puerarin by PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated puerarin liposomes were greater than that by puerarin drop solution and uncoated liposomess (P < 0.01), meanwhile the PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated liposomes were better than other ratios of coated liposomes for improvement of corneal penetration (P < 0.01). CONCLUSION: The PAMAM coated liposomes is able to enhance the corneal penetration of puerarin and promising as an ocular drug carriers. PMID- 20349712 TI - [Pharmaceutical properties of novel liposomes containing total alkaloids from seed of Strychnos nux-vomica]. AB - OBJECTIVE: To prepare the novel liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC) and soybean phosphatidylcholine (SPC) containing the total alkaloids from seed of Strychnos nux-vomica, and to compare the pharmaceutical properties of the novel liposomes with the corresponding HSPC or SPC liposomes. METHOD: The total alkaloids were extracted from seeds of S. nux vomica. and further purified. Novel liposomes containing the total alkaloids were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique. Pharmaceutical properties such as encapsulation efficiency (EE), size, zeta potential and drug release profile of novel liposomes and corresponding HSPC or SPC liposomes were compared intensively. RESULT: For novel liposomes, HSPC-SPC (1:3) was the best ratio which has the highest EE. At the drug/lipid weight ratio of 1:6, the EE of novel, SPC and HSPC liposomes were (73.6 +/- 2.9)%, (62.9 +/- 1.8)% and (54.7 +/- 1.0)% (n = 3), respectively. Compared with the corresponding SPC or HSPC liposomes, the size of novel liposomes was obviously decreased but the zeta potential was not different. The results of drug release showed that the novel liposomes were more stable than the SPC liposomes in the presence of rat plasma CONCLUSION: Taken together, high encapsulation efficiency improved stability in blood, and relative low price of phospholipids of the novel liposomes, indicate that the novel liposomes may act as promising carriers for anti-tumor traditional Chinese medicine. PMID- 20349713 TI - [Preliminary study to investigate dynamic extract process of Huanglian Jiedu Tang and the mechanism of subsidence produce]. AB - OBJECTIVE: To study the phenomenon of subsidence emergence in the process of Huanglian Jiedu Tang decoction extraction, and the mechanism of subsidence emergence. METHOD: UV was applied to determine the concentration of total alkaloids and total flavones; Simultaneous determination of berberine, jatrorrhizine, palmatine, baicalin and geniposide were carried out by HPLC; The solid holdup and precipitation rate were calculated by the formula. The relativity among these parameters was analyzed by the SPSS software program. RESULT: The contains of berberine, jatrorrhizine, palmatine in total alkaloids showed a good correlation with total alkaloids. The correlation between baicalin and total flavones was lower than that between geniposide and total flavones. Compared to precipitation rate, solided hold up shows a larger relevance with index component CONCLUSION: With the change of time, the total alkaloids represented by berberine alkaloids and baicalin at a certain concentration can be regarded as the equilibrium point, or one generated by the critical point of precipitation, the reaction can generate "sediments"; because "precipitation objects" generated, reducing the concentration of the above-mentioned components, destroy the" balance". The relevant components of herbal medicine increased dissolution rate, at the same time might partly dissolved sediment, reaching a new equilibrium state. PMID- 20349714 TI - [Pressurized liquid extraction of Tripterygiumw wilfordii polyglycosides and optimization of extraction conditions]. AB - OBJECTIVE: To investigate the extraction method of polyglycosides from Tripterygium wilfordii. METHOD: The extraction method of pressurized liquid extraction was employed and chromogenic colorimetric technique were used for quantitative analysis. Based on the single-factor experiment, according to the center combination design this paper used three factors and three levels of response surface methodology for process optimization. RESULT: The optimized conditions were as follows: ratio of solid to liquid was 1:9.5, at the temperature of 115 degrees C for 80 minutes, the actual extract ratio and purity of polyglycosides obtained were 0.21% and 0.52%, respectively. CONCLUSION: The method of pressurized liquid extraction has obvious advantages over conventional reflux extracting. PMID- 20349715 TI - [Solubilization of O/W microemulsion for volatile oil from Houttuynia Cordra]. AB - OBJECTIVE: To study the solubilization of O/W microemulsion system for volatile oil from Houttuynia Cordra and determine the formulation of its microemulsion. METHOD: The solubilization curve was drawn from pseudo-ternary phase diagram plotted by using the method of titration. The microemulsion's effect on solubilization for volatile oil from Houttuynia Cordra was systematically studied and the difference solubilization effects between colloid fluid and microemulsion were compared. RESULT: Excipient varieties and amount of microemulsion had effects on solubilization for volatile oil from Houttuynia Cordra. The formulation of its microemulsion was determined and we chose medium-chain triglycerides as oil phase, polyoxyethylene castor oil EL-35 as surfactant, propylene glycol as cosurfactant and the surfactant to cosurfactant ratio was 2. CONCLUSION: Suitable microemulsion formulation can solubilize volatile oil from Houttuynia Cordra and it can provide research foundation for further development of microemulsion preparation for volatile oil from Houttuynia Cordra. PMID- 20349716 TI - [2-Pyridinethiolate derivatives from branches and leaves of Polyalthia nemoralis and their cytotoxic activities]. AB - OBJECTIVE: To investigate the active constituents of the branches and leaves of Polyalthia nemoralis. METHOD: The compounds were isolated and purified by silica gel, macroporous adsorption resin and Sephadex LH-20 column chromatographic methods. Their chemical structures were elucidated on the basis of physicochemical properties and spectral data. RESULT: Eight compounds were isolated and identified as: zincpolyanemin (1), nickel bis-(pyridine-N-oxide-2 thiolate) (2), cupric bis (pyridine-N-oxide-2-thiolate (3), 2-methanesulfonyl pyridine (4), 2-pyridinethiolate N-oxide (5), 2,2'-dithiodipyridine (6), 2 thiohydroxypyridin-N-oxide-2-S-beta-D-gluco pyranoside (7) and pyridine-N-oxide (8), respectively. CONCLUSION: Compounds 2, 4-6, 8 were new natural products. The bioassays in vitro against five human tumor cell lines with MTT method showed stronger cytotoxic activities (IC50 0.05-0.09 mg x L(-1)) for compounds 1-3 and 6, and weaker cytotoxic activities (IC50 5.49-7.71 mg x L(-1)) for compound 5. PMID- 20349717 TI - [Chemical constituents of Incarvillea younghusbandii]. AB - OBJECTIVE: To study the chemical constituents of Incarvillea younghusbandii. METHOD: The chemical constituents were isolated by various column chromatographic methods and structurally identified by NMR and MS evidence. RESULT: Fifteen compounds were obtained and identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), boschniakinic acid (11), tert-O-beta-D-glucopyranosyl-(R)-heraclenol (12), 5 methoxy-8-O-beta-D-glucopyranosyloxypsoralen (13), 1'-O-beta-D-glucopyranosyl-3 hydroxynodakenetin (14) and phenylethyl-O-beta-D-glucopyranosyl-(1-->2)-beta-D glucopyranoside (15). CONCLUSION: All of these compounds were isolated from this plant for the first time and most of them are furocoumarins. PMID- 20349718 TI - [Research on liposoluble ingredients of Quchiling]. AB - OBJECTIVE: To study the liposoluble ingredients of Quchiling (LQ), which enter the blood and the brain,and to confirm the active ingredients of LQ in vivo. METHOD: Serum pharmacochemistry and gas chromatography mass spectroscopy were used to analyze ingredients of LQ entering the blood and the brain. RESULT: There were eleven ingredients of LQ to enter the blood and six ingredients of LQ to enter the brain. CONCLUSION: It is confirmed that eleven ingredients of LQ entered the blood, which are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, schisantherrin A, schisantherrin B, schisantherrin C, delta-cadinene, delta-cadinol and calamendiol in the blood, and that six ingredients are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B and calamendiol in the brain. PMID- 20349719 TI - [Simultaneous determination of five nucleotides in Bulbus Fritillariae by RP HPLC]. AB - A high-performance liquid chromatography method was developed for determination of five nucleotides in Bulbus Fritillariae. The five nucleotides were uridine, adenine, guanosine, thymidine, adenosine, respectively. A Welch materials XB-C18 column (4.6 mm x 250 mm, 5 microm) was used and the chromatographic separation was achieved using 5 mmoL x L(-1) ammonium acetate-acetic acid buffer solution (pH 4.30, B) and methanol (A) as mobile phases, the gradient elution program: 0 10 min, 0%-1% A, 10-20 min, 1%-5% A, 20-25 min, 5% A, 25-35 min, 5%-30% A, 35-37 min, 30%-0% A, 37-40 min, 0% A with a flow rate of 1 mL x min(-1) and monitored at 260 nm, the injection volume was 20 microL. The peak areas of nucleotides and the concentrations showed a good linear relation ranged from 0.24 to 13.60 mg x L(-1), r > 0.9983. The intra- and inter-day pecision results were adequate with the RSDs of 2.1% or below. The repeatability was good and the RSD were smaller than 5.5%. The recoveries of nucleosides were in the range of 93.55% and 101.9%, RSD < 3.0%; The order of nucleotides contents in different Bulbus Fritillariae was F. hupehensis > F. thunberqii > F. cirrhosa approximately F. ussuriensis. The method is simple, convenient and accurate. It can be used for the determination of nucleosides and supplying evidence for exploiting and applying of Bulbus Fritillariae. PMID- 20349720 TI - [Effects of salvianolic acid B on lipid peroxidation and metalloproteinase-2 activity in fibrotic liver in rat]. AB - OBJECTIVE: To investigate the mechanism of salvianolic acid B (Sal B) action against liver fibrosis through preventing lipid peroxidation and regulating MMP-2 activity in liver. METHOD: The liver fibrotic model was induced through intraperitoneally injection of DMN at a dose of 10 microg x kg(-1) for every other day and lasting for 4 weeks. Sal B was administered (10 mg x kg(-1)), and perindopril (5 mg x kg(-1)) was used as positive control. Hepatic inflammation and collagen were observed with HE and sirius red staining. The liver function including serum ALT, AST activity, Alb and total bilirubin (T. Bil) level were determined. The hepatic lipid peroxidation including SOD and GST activities and GSH content were measured. Hepatic hydroxyproline (Hyp) content was detected with Jamall's method. The activity of metalloproteinase was assayed by gelatin zymography. The expressions of alpha-SMA, Col I in liver tissue were analyzed by Western blot. RESULT: The model rats had higher serum T. Bil content, ALT and AST activities but lower Alb content than the normal rats, also had remarkable inflammatory necrosis and collagen deposition in liver, with much higher Hyp content, protein expression of alpha-SMA and collagen I and MMP-2 activity in liver, but had a decreased GSH content, SOD and GST activities. Both Sal B and perindopril attenuated hepatic injury and collagen deposition in model rats, decreased serum ALT activity and hepatic Hyp content, down-regulated alpha-SMA and collagen I protein expressions and metalloproteinase-2 activity than those in the model group, but increased SOD activity and GSH content, and Sal B decreased serum T. Bil content and increased GST activity. Sal B had a much better comprehensive actions than perindopril. CONCLUSION: Sal B has a good preventive action against liver fibrosis, the action mechanism is related to the prevention from lipid peroxidation and down-regulation of metalloproteinase-2 activity in fibrotic liver. PMID- 20349721 TI - [Study on IgG promoter as probe to evaluate safety of injections in pre-clinic]. AB - OBJECTIVE: To construct an effective system screening and evaluating possible injections and components inducing allergy type II. METHOD: Transfect IgG promoter-regulated green fluorescent protein expressing plasmid into RPMI-8226 cell. The number of fluorescent cells after drug treatment was calculated and statistically evaluated. RESULT: Tween 80 can suppress the expression of IgG effectively, and puerarin has activity of stimulating IgG expression, and the system has no response to KCl-treatment. No effect of Yuxingcao (Herba Houttuyniae) injection on this system is observed. CONCLUSION: IgG promoter-drove green fluorescent protein expressing cell line can be used as system screening injections and components inducing allergy type II based on stimulating IgG promoter activity. Tween 80 can suppress the expression of IgG at the transcriptional level. Four batches of Yuxingcao injection cannot induce allergy type II by activating IgG expression. PMID- 20349722 TI - [Effects of methyl protodioscin on [Ca2+]i and ATPase activity in cardiomyocytes and analysis of mechanisms]. AB - OBJECTIVE: To study the effects of methyl protodioscin on the [Ca2+]i and the ATPase activity in cardiomyocytes, as well as their mechanisms. METHOD: The cardiomyocytes were randomly divided into three groups, the control group treated with no serumal DMEM, the MPD group treated with MPD and the dilthiazem group treated with dilthiazem. Fluorospectrophotometer was used to determined the level of myocardial cell intracellular Ca2+ [Ca2+]i. In the experiment of ATPase activity on cellular membrane, the cardiomyocytes were randomly divided into two groups, the control group treated with no serumal DMEM, the MPD group treated with MPD. The activity of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and Mg2+-ATP ATPase were determined. The quantitative analysis of SERCA2a mRNA expression was studied by RT-PCR that the groups and treatments in cardiomyocytes same as the experiment for ATPase activity assay. RESULT: Under the quiescent condition, compared to the control group, the level of [Ca2+]i in cardiomyocytes of the MPD group and dilthiazem group was no different. After treatment with 40 mmol x L(-1) KCl, [Ca2+] was significantly lower in the MPD group and the dilthiazem group, and the intensity of peak value in time course of 60 s, the dilthiazem group and the MPD group also were lower than the control group (P < 0.001). Ca2+-Mg2+-ATPase and Na+-K+-ATPase in cultured rat were increased after treated with MPD compared to treatment with no serumal DMEM (P < 0.05, P < 0.01), but Mg2+-ATPase in these groups had no different. The expression of SERCA2a mRNA between the MPD group and the control group was no different. MPD could not up-regulated or down-regulated SERCA2a in endocytoplasmic reticulum. CONCLUSION: Methyl protodioscin could block the volt dependent form calcium channel in cellular membrane, and up-regulate the function of sodium pump and calcium pump, so that it could remain low calcium in the internal environment in cardiomyocytes. PMID- 20349723 TI - [Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes]. AB - OBJECTIVE: To observe the effects of tetrahydropalmatine, dehydrocorydaline, berberine and palmatine on anoxia and peroxidation injuries in cardiomyocytes, and study the marterial basis of the anti-ischemia effect on myocardium of Rhizoma Corydalis. METHOD: Neonatal rat cardiomyocytes were cultured in vitro, and subjected to an anoxia-reoxia and the hydrogen peroxide injury models. The four compounds were added into the culture medium. The cell viability was measured by MTT method to determine the safe concentrations and the anti-hydrogen peroxide injury effects of the compounds. The LDH activity in culture mediums was measured with the enzyme reaction dynamics-monitoring method to value the anti anoxia injury effects of the compounds. RESULT: At most up to 500 mg x L(-1), tetrahydropalmatine showed no sinificant effect on the cell viability, while dehydrocorydaline, berberine and palmatine significantly decreased the cell viability, exceeding 6.3, 0.6 and 6.3 mg x L(-1), respectively (P < 0.05 or P < 0.01). Tetrahydropalmatine, dehydrocorydaline, berberine and palmatine significantly inhibited LDH leakage induced by anoxia-reoxia injury, at concentrations of 50-100, 1.25-5, 4 and 30 mg x L(-1), respectively (P < 0.05 or P < 0.01). None of the four compounds showed significant effect on the hydrogen peroxide injury. CONCLUSION: The anti-ischemia effect in myocardium of Rhizoma Corydalis is related to the direct protective effects on cardiomyocytes of its components, tetrahydropalmatine, dehydrocorydaline, berberine and palmatine, amomg which tetrahydropalmatine and dehydrocorydaline are the most important, the former with high safety and low efficacy, while the latter with low safety and high efficacy. And the direct protective effects on cardiomyocytes of these four components may be attained through mechanisms other than anti-peroxidation. PMID- 20349724 TI - [Impact of salvianolic acid-B on TGF-beta1-induced HK-2 epithelial-mesenchymal transition]. AB - OBJECTIVE: To investigate the effect of salvianolic-acid B (SA-B) on epithelia mesenchymal transition in human renal proximal tubular cells (HK2), induced by transforming growth factor beta1 (TGF-beta1). METHOD: Epithelia-mesenchymal transition (EMT) was induced with TGF-beta1 in HK2 cultured in vitro. Different concentrations (2, 5, 10, 20 microg x L(-1)) and stimulant periods (12, 24, 48 h) were tried to find the perfect condition for EMT. At the same time bone morphogenetic protein-7 (BMP-7, positive control) and the SA-B intervention were given to observe their effect on EMT. Western blot and immunofluorescent microscopy were used to analyze the expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA) in HK2. RESULT: BMP-7 significantly inhibited the down regulation of E-cadherin and the up-regulation of alpha-SMA induced by TGF-beta1 (P < 0.05), and SA-B significantly inhibited the up-regulation of alpha-SMA expression induced by TGF-beta1 (P < 0.05), but not the down-regulation of E cadherin induced by TGF-beta1. CONCLUSION: SA-B and BMP-7 can inhibit TGF-beta1 induced EMT in HK2. Their common role is to inhibit the up-regulation of alpha SMA, and the effect of SA-B on the regulation of E-cadherin needs further study to be confirmed. PMID- 20349725 TI - [Protective effects of resveratrol on neonatal rat cardiomyocyte lesion induced by hypoxia]. AB - OBJECTIVE: To investigate the effects of resveratrol (Res) on neonatal rat cardiomyocyte lesion induced by hypoxia. METHOD: The cardiomyocyte of neonatal rats were cultured in vitro and the model of cardiomyocyte hypoxia was established. The cardiomyocyte vitalities were determined by MTT assay, the HIF 1alpha expression levels in myocardial cells was detected by immunohistochemical, the activities of peroxidase (GSH-Px) and lactate dehydrogenase (LDH) were measured as well. RESULT: After the administration of hypoxia for 24 hours, the HIF-1alpha expression in myocardial cells was significantly increased. The LDH level in the culture medium was increased from (93.07 +/- 15.84) U x L(-1) to (750.77 +/- 181.51) U x L(-1) (P < 0.01). The intracellular GSH-Px activity was decreased from (46.96 +/- 8.36) U x mL(-1) to (27.13 +/- 4.76) U x mL(-1) (P < 0.05). Res 25, 50 and 75 micromol x L(-1) could dose-dependently inhibit the raising of the HIF-1alpha expression in myocardial cells induced by hypoxia. The LDH activities were decreased dose-dependently to (486.17 +/- 69.97), (189.43 +/- 32.07), (155.34 +/- 29.57) U x L(-1), respectively (P <0.05 or P <0.01). The GSH Px activities were increased dose-dependently (33.55 +/- 6.34), (37.67 +/- 6.73), (41.44 +/- 7.91) U x mL(-1) (P < 0.05 or P < 0.01). CONCLUSION: Res has a protective effect on neonatal rat cardiomyocyte lesion induced by hypoxia. PMID- 20349726 TI - [Preliminary study of metabonomcs on aqueous extract of Evodia rutaecarpa in sprague-dawley rats]. AB - OBJECTIVE: To study the change of endogenous metabolites of SD rats administrated of aqueous extract of Evodiae rutaecarpa. METHOD: Six SD rats had been successively administrated aqueous extract of E. rutaecarpa (0.3857 g x kg(-1)) for 33 days. An agilent 1200 6410 triplequadrupole mass spectrometer was used for the analysis of endogenous metabolites in rat urine samples. These data was analyzed by the principal component analysis (PCA) and PLS-DA using the SIMCA-P 10.0 software. RESULT: The significant difference in metabolic profiles between the control group and the dosed group was well observed by PCA of the MS data. CONCLUSION: The E. rulaecarpa has changed the endogenous metabolites of SD rats. This work can provide the base for the further research on the interpretation of drug property of E. rulaecarpa. PMID- 20349727 TI - [Effect of oxymatrine on JAK/STAT iteral in rat lung tissue with sepsis]. AB - OBJECTIVE: To explore the effects of oxymatrine (OMT) on JAK/STAT iteral in rat lung tissue with sepsis. METHOD: Fifty-six male SD rats were randomly divided into 6 groups: sham operation group, model (CLP) group, CLP + OMT high, middle, low-dose groups (52, 26, 13 mg x kg(-1), vena caudalis bolus), and positive control group (dexamethasone, 10 mg x kg(-1), vena caudalis bolus) to observe the effects of oxymatrine on the ratio between wet weight of the lung and dry weight of the lung (W/D) and pulmonary coefficient, gross changes and pathological changes examined with lightmicroscope in the pulmonary tissue. Changes in JAK2 and STAT3 activity in the pulmonary tissue were determined by immunohistochemical method. Tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in pulmonary tissue were determined by radioimmunoassay. RESULT: OMT could decrease significantly the JAK2 and STAT3 positive reaction and activity in the pulmonary tissue (P < 0.05). TNF-alpha and IL-6 levels in pulmonary tissue homogenate decreased markedly (TNF-alpha decreased 36%, 26%, 16% and IL-6 decreased 46%, 39%, 24% on CLP + OMT 52, 26 mg x kg(-1) and 13 mg x kg(-1) groups. P < 0.05 or P < 0.01). OMT could decrease the ratio between wet weight of the lung and dry weight of the lung and the pulmonary coefficient, improve the condition of pulmonary hyperemia, edema, infiltrate of heterophil granulocyte and emerge of asphyxial membrane, and alleviate the inflammatory reaction. And the results were equal to those of the positive control (CLP + dexamethasone) group. CONCLUSION: OMT can inhibit JAK/STAT iteral activity and reduce the expression of proinflammatory factor (TNF-alpha, IL-6) and antagonize the lung injury in a rat model of sepsis. PMID- 20349728 TI - [Inhibitive effect of polypeptide extract from scorpion venom on repopulation in H22 tumor cell during chemotherapy]. AB - OBJECTIVE: To observe the inhabitive effect and mechanism of polypeptide extract from scorpion venom (PESV) on repopulation in H22 tumor cell during chemotherapy. METHOD: H22 tumor cells were injected into 96 mice subcutaneously, then mice were divided into 4 groups radomly: Model, low-dose-PESV, high-dose-PESV, and control. Reppulation model was established by 5-Fu treating mice with H22. Four groups was treated differently, 6 mice of each group was sacrificed every 7 days, measured tumor volume twice one week. The expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), CD105 microvessel density (CD105-MVD) and platelet derived growth factor (PDGF) in H22 tumor issue was observed by using immunohistochemistry and grey analysis, the relation of VEGF and MVD was affirmed by correlation analysis. RESULT: In control group tumor volume of H22 increased quickly in 13-24 day, and all mice died before 27 day. In model tumor volume increased quickly before 17, in 17-22 day slowly, after 22 day quickly again, and all the mice died before 31 day. In low and high dose PESV, tumor volume added slowly, and only in 17 day there was significant difference between these two groups. Immunohistochemistry showed, PCNA expression of model group in 31 day was higher than in 21, 28 day, the expression level of high and low PESV group was lower than model group all the time, only in 17 day there was significant difference between high and low PESV group. Immunohistochemitry showed, compared with high and low dose PESV group, CD105-MVD of model group was higher in 21, 28 day (P < 0.05) and in 35 day (P < 0.01), and no difference was found between high and low dose PESV. VEGF expression of model group in 35 day was higher than in 21, 28 day (P < 0.01), and model group higher than high and low dose PESV in 21, 28, 35 day. The expression of PDGF in model decreased gradually, in high and low dose PESV, the expression was lowest in 21 day. In day 35 high dose PESV higher than low dose PESV. There was positive correlation (r = 0.669) between VEGF expression and CD105-MVD. CONCLUSION: PESV can inhabit repopulation of H22 tumor cell during chemotherapy, and the mechanism maybe is through anti-angiogenesis and nomalizing tumor vessels. PMID- 20349729 TI - [Neuroprotective effect of extract of Ginkgo biloba against excitotoxicty compared with ginkgolide B in neuron cell of rat]. AB - OBJECTIVE: To observe the effect of the extract of Ginkgo biloba (EGb761) and the components isolated from the extract named ginkgolide B (GB) against damage of glutamate in pretreatment modes so that determine their application value and approach. METHOD: Based on glutamate-induced excitotoxicity to primary cultures from neonatal Sprague-Dawley (SD) rat hippocampal neuron, our experiment utilized trypan blue, TUNEL and LDH to study the effect of EGb761 and GB on neuron in different doses pretreatment modes, as well as to compare with the NMDA receptor uncompetitive antagonist-MK-801. RESULT: EGb761 and GB can recrease cell viability, reduce apoptosis rate and decrease LDH leakage in different degree and depended on dose in certain range. The maximal protection was achieved at a concentration of 100 mg x L(-1), 100 micromol x L(-1), but inferior to MK-801 (10 micromol x L(-1)). The protective effect of GB is superior to EGb761. CONCLUSION: Treatment with EGb761 and GB could protect the neurons against glutamate-induced injury. The maximal protection of GB was achieved by pretreatment is superior to EGb761, so its precautionanary intervention to high-risk population could have more value. PMID- 20349730 TI - [Effects of cryptotanshinone on proliferation and apoptosis of Hela cell line of cervical cancer]. AB - OBJECTIVE: To investigate the proliferation effects and apoptosis induction of cryptotanshinone on Hela cell line of cervical cancer. METHOD: The MTT assay was used to detect the growth inhibition rates of Hela cells at 24, 48, 72 h which cultured with cryptotanshinone in different concentrations. The cell cycle distribution and apoptosis were measured by flow cytometry. The protein expressions of E6, p53 and p21 were studied by Western blot. RESULT: The different concentrations (0.5-16 mg x L(-1)) of cryptotanshinone had cytotoxicity on Hela cells, which were clearly dose and time-dependent. The IC50 of 24, 48, 72 h were 17.8, 8.17, 6.55 mg x L(-1), respectively. Cells were treated with cryptotanshinone which had significant effects on cell cycle of Hela cell, and induced apoptosis. Western blot showed cryptotanshinone decreased expressions of HPV E6 and increased expressions of p53 and p21 proteins. CONCLUSION: Cryptotanshinone had significant cytotoic and radiosensitization effects on cervical cancer Hela cells. One of the mechanism may be that it might make significant G0/G1 phase arrest and induced apoptosis, a decrease in S phase, and restore the function of p53 to induce apoptosis in Hela cells to kill the tumor cell. PMID- 20349732 TI - [Discuss on effect of physical environmental factors on nature of Chinese materia medica]. AB - Nature of Chinese materia medica is the nucleus in the theory of Chinese material medica, according to the recognition of Traditional Chinese Medicine, which is the character of the drug related on curative effect. Nature and efficacy of a drug is through the medical material, then, physical environment, including the temperature, humidity, atmospheric water, wind, topography, soil, micro-organism, and so on, influence the growth and development of the medical meterial. In this paper, we researched the explanation on nature of Chinese materia medica in the medical books of past dynasties, combined with the modem research, analyzed the relationship between generative reception and physical environmental factors, and discussed the effect of physical environmental factors on nature of Chinese materia medica. We indicated that the formation of Chinese materia medical nature is that the drug receptive the change of physical environmental factors, and resulted by the synthetic action of the factors, such as climate, soil, biology, topography, etc. PMID- 20349731 TI - [Epileptic seizure-like effect of Sophora alkaloid sophoridine on experimental animals]. AB - OBJECTIVE: To investigate the epileptic seizure-like effect of Sophora alkaloid sophoridine on electroencepholography (EEG) and its possible characteristic and the mechanism of the seizure-like effect. METHOD: Chronic electron implantation was employed for the intracranial electroencepholography (IEEG) recording in rat, and the traditional anti-seizure drugs were for the mechanism study in mice. RESULT: Compared with the medial perforant path (PP) area and the temporal cortex (TC), the granule cells in hippocampus dentate gyrus (DG) area is more sensitive in the kindling effect by sc sophoridine. Under-threshold hypnotic dosage of diazepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage of it can block the maximal electroconvulsive shock (MES) seizure. CONCLUSION: Sophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and the diazepam is the ideal agent for the treatment. PMID- 20349733 TI - Employers, workers, and the future of employment-based health benefits. AB - EBRI'S BIANNUAL POLICY FORUM: This Issue Brief summarizes presentations at EBRI's 65th biannual policy forum, held in Washington, DC, on Dec. 10, 2009, on the topic, "Employers, Workers, and the Future of Employment-Based Health Benefits." The forum brought together a wide range of economic, benefits, management, and labor experts to share their expertise at a time when major health reform legislation was being debated in Congress. The focus: How might this affect the way that the vast majority of Americans currently get their health insurance coverage? THE EMPLOYMENT-BASED HEALTH INSURANCE SYSTEM: Most people who have health insurance coverage in the United States get it through their job: In 2008, about 61 percent of the nonelderly population had employment-based health benefits, 19 percent were covered by public programs, 6 percent had individual coverage, and 17 percent were uninsured. DIFFERENCES, AGREEMENTS: Not surprisingly, given the deep conflicts that exist over President Obama's health reform plan and the different bills that have passed the House and Senate, benefits experts also do not agree on what "health reform" will mean for either workers or employers. Views ranged from "Will anyone notice?" to predictions of great upheaval for workers and their employers, patients and health care providers, and the entire U.S. health care system. One point of consensus among both labor and management representatives: Imposing a tax on health benefits is likely to cause major cuts in health benefits and might result in structural changes in the employment-based benefits system. A common disappointment voiced at the forum was that the initial effort to reform the delivery and cost of health care in America gradually became focused on just financing and coverage of health insurance. RECENT TRENDS: The ever-rising cost of health insurance affects different employers and workers in different ways--with small employers and low wage workers being the most disadvantaged. With health premiums having risen almost five times as much as the overall rate of inflation since 2000, employers face unsustainable cost increases in health benefits. For a minimum-wage worker, the cost of family coverage (averaging about $13,700 a year in a small firm) exceeds their total annual income (about $11,500 a year). Small employers, if they offer health benefits at all, pay proportionately more than large employers for the same health coverage. PUBLIC OPINION: As reflected by the debate in Congress, the American public has conflicted opinions on both the U.S. health care system and on reform: Surveys find that people tend to be satisfied with the quality of their own care but not with costs and access, and a majority rates the system as fair or poor. Opinions divide sharply along partisan lines. PERSPECTIVES: While large employers tend to express continued commitment to health benefits, small employers see themselves strongly disadvantaged by the current system. Consultants report many employers privately want to drop benefits to control costs, but realize there are risks to doing so and none wants to be first. Employers express strong interest in wellness and disease management programs as a way to control costs, even though some experts say there is no evidence these work. Consumer-driven health plans are expected to continue their slow rate of growth. PMID- 20349734 TI - Signing, dating, and timing your verbal orders: are you in compliance? PMID- 20349735 TI - Will EMRs help verbal order compliance? PMID- 20349736 TI - New medical staff standard still ruffling feathers. PMID- 20349737 TI - Do new nurses have QI skills, understanding? PMID- 20349738 TI - Quality improvement, orientation for new nurses. PMID- 20349739 TI - Surveyors focus on informed consent, nails. PMID- 20349740 TI - Reader's perspective. The safety and efficiency benefits of using CPOE systems are overstated. PMID- 20349741 TI - Forecasters predict spend growth. PMID- 20349742 TI - Unraveling the claims snarl. PMID- 20349743 TI - Ramping up on wireless. PMID- 20349744 TI - All systems go. PMID- 20349745 TI - Navicure grows its EDI business. PMID- 20349746 TI - Feet to the fire. PMID- 20349747 TI - Spotlight on servers. PMID- 20349748 TI - Measuring cognitive services. PMID- 20349749 TI - Blood transport method for chromosome analysis of residents living near Semipalatinsk nuclear test site. AB - A study was conducted to compare the storage conditions and transportation period for blood samples collected from residents living in areas near the Semipalatinsk nuclear test site (SNTS). Experiments were performed to simulate storage and shipping environments. Phytohaemagglutinin (PHA)-stimulated blood was stored in 15-ml tubes (condition A: current transport method) in the absence or in 50-ml flasks (condition B: previous transport method) in the presence of RPMI-1640 and 20% fetal bovine serum (FBS). Samples were kept refrigerated at 4 degrees C and cell viability was assessed after 3, 8, 12 and 14 days of storage. RPMI-1640, 20% FBS and further PHA were added to blood samples under condition A in 50-ml flasks for culture. Whole-blood samples under condition B were directly incubated without further sub-culturing process, neither media nor PHA were added, to adopt a similar protocol to that employed in the previous transport method. Samples in condition A and condition B were incubated for 48 hr at 37 degrees C and their mitotic index was determined. The results showed that viable lymphocytes were consistent in both storage conditions but the mitotic index was higher in condition A than in condition B. Although further confirmation studies have to be carried out, previous chromosomal studies and the present experiment have shown that PHA-stimulated blood could be stored without culture medium for up to 8 days under condition A. The present results will be useful for cytogenetic analysis of blood samples that have been transported long distances wherever a radiation accident has occurred. PMID- 20349750 TI - Arterial mechanical impedance is a sensitive stress response monitor during general anesthesia. AB - Arterial mechanical impedance is a characteristic of arterial dynamics that is determined by photoplethysmographic amplitude and direct arterial pressure, while mechanical impedance is indicated by stiffness, viscosity, and inertia. We compared the parameters of mechanical impedance and photoplethysmographic amplitude to estimate the magnitude of stress response in patients undergoing general anesthesia by measuring direct arterial pressure. After sedating each patient with propofol, photoplethysmographic amplitude and mechanical impedance were measured as baseline control values, then 3 min after fentanyl administration (2 microg kg(-1)), the parameters were measured again as post fentanyl values. Thereafter, a direct laryngoscopy procedure was performed and post-laryngoscopy values for the parameters were determined. The magnitudes of response to each event were compared by using the ratio of the measurements from the preceding event. Then, comparisons of the magnitudes were performed after coordinating each response in the same direction. Our results showed that both stiffness and viscosity of mechanical impedance had greater variations than photoplethysmographic amplitude. In conclusion, we propose stiffness and viscosity derived from arterial mechanical impedance as sensitive parameters to monitor stress responses during general anesthesia. PMID- 20349751 TI - Practical use of airway pressure release ventilation for severe ARDS--a preliminary report in comparison with a conventional ventilatory support. AB - Airway pressure release ventilation (APRV) is a ventilatory mode that allows unsupported spontaneous breathing at any phase of the ventilatory cycle with high mean airway pressures. We hypothesized that use of APRV might produce potential beneficial effects on oxygenation, reducing mortality in patients with severe acute respiratory distress syndrome (ARDS) in comparison with synchronized intermittent mandatory ventilation (SIMV) as a conventional mode of ventilation. We retrospectively reviewed data of 58 patients with severe ARDS (the ratios of partial arterial oxygen tension to fraction of inspired oxygen, PaO2/F(I)O2 ratio <150). The patients' data were divided into two groups: SIMV-group and APRV group. Patients' backgrounds, oxygenation on day 0, 1, 3, 5 and 7 following initiation of each mode, vasopressor dependence, duration of ventilation, duration of ICU stay, and mortality in ICU were analyzed. PaO2/F(I)O2 ratios were statistically higher in the APRV-group (APRV vs. SIMV on day 1, 3, 5, 7: 201.6 +/ 76 vs.150 +/- 59.1, 256.7 +/- 71.5 vs.182.1 +/- 65.4, 268.8 +/- 73.3 vs. 204.6 +/- 72.8, and 263 +/- 74.5 vs. 204.1 +/- 67.1, respectively, p<0.05). Vasopressors were less used (p=0.018), and mortality in ICU tended to be lower in the APRV group (31%) than in the SIMV group (59%) (p=0.050). Use of APRV in patients with severe ARDS appears to be associated with improvements in oxygenation, and a trend toward lower mortality in ICU. No significant adverse effects were observed. Prospective controlled studies are required to confirm the benefits of this ventilatory mode in comparison with conventional methods for severe ARDS. PMID- 20349752 TI - Benefits of early anti-retroviral therapy in patients with HIV-TB co-infection. PMID- 20349753 TI - Association of 22 cytokine gene polymorphisms with tuberculosis in Macedonians. AB - OBJECTIVE: To examine the possible role of 22 cytokine gene polymorphisms in host susceptibility to or protection against tuberculosis (TB) in Macedonians. METHOD: 301 healthy unrelated individuals and 75 patients with pulmonary TB were studied. Cytokine genotyping was performed by PCR with sequence-specific priming (PCR-SSP) (Heidelberg kit). RESULTS: TNF-alpha-238/G, IL-1R psti1970/C, IL-1beta + 3962/T:T, IL-4-1098/T:T, IFNgamma utr5644/A:A, IL-10-1082/G:G, IL-4-590/C:C, IL 10/ATC, IL-4/TCT, IL-4/TCC, IL-10/ATC:GCC, IL-4/TCT:TTT, IL-4/TCC:TTC, IL 10/GCC:GCC and IL-4/TCC:TCC were positively associated with TB, while protective association was identified for IL-4-098/G, IL-1beta + 3962/C, IFNgamma utr5644/T, IL-1beta + 3962/C:T, IL-4-1098/G:T, IL-4-590/C:T, IFNgamma utr5644/A:T, IL-4/GCC, IL-4/TTC and IL-4/GCC:TTC. CONCLUSION: These results suggest that some cytokine polymorphisms are significantly associated and affect host susceptibility/resistance to TB in Macedonians. PMID- 20349754 TI - Assessment of long term status of sputum positive pulmonary TB patients successfully treated with short course chemotherapy. AB - BACKGROUND: Long term status of pulmonary tuberculosis (PTB) patients treated with short course chemotherapy (SCC) regimens remains unknown. OBJECTIVE: To assess the clinical, bacteriological, radiological status and health related quality of life (HRQoL) of PTB patients 14-18 years after successful treatment with SCC. METHODOLOGY: In a cross-sectional study, cured PTB patients treated during 1986-1990 at the Tuberculosis Research Centre (TRC) were investigated for their current health status including pulmonary function tests (PFT). The St Georges respiratory questionnaire (SGRQ) was used to assess the HRQoL. RESULTS: The mean period after treatment completion for the 363 eligible participants was 16.5 yrs (range 14-18 yrs., 84% coverage); 25 (7%) had been re-treated and 52 (14%) died. Among the investigated, 58 (29%) had persistent respiratory symptoms; 170 (86%) had radiological sequelae but none had active disease. Abnormal PFT was observed in 96 (65%) with predominantly restrictive type of disease in 66 (45%). The SGRQ scores for activity and impact were high implying impairment in HRQoL. CONCLUSION: Assessment of long term status of cured PTB patients showed an impairment of lung functions and HRQoL highlighting the need to address these issues in the management of TB that may provide added value to patient care. PMID- 20349755 TI - Mycobacterial ES-31 serine protease--a biomarker for mycobacterium tuberculosis- a preliminary report. AB - There is a need for simple and reliable method to identify Mycobacterium tuberculosis from AFB smear positive cases. Utility of mycobacterial ES-31 serine protease as a marker to detect Mycobacterium tuberculosis bacilli was explored using Fluorescein isothiocyanate conjugated anti-ES-31 serine protease antibody. The presence of ES-31 serine protease in bacilli was indicated by green fluorescence on the cell surface. Green fluorescence was observed with M.tb.H37Ra bacilli and M.tb.H37Rv bacilli while no Fluorescence was observed with M. chelonae, Nocardia farcinicum as well as in E. coli showing the usefulness of ES 31 serine protease as a marker for identification of mycobacterium tubercle bacilli in cultures. PMID- 20349756 TI - Comparing outcomes in new pulmonary sputum positive and sputum negative cases under RNTCP in rural India. AB - SETTING: The study was carried out at the Bagula TU, Nadia, West Bengal, India. OBJECTIVE: To find out the treatment outcomes of new smear negative cases, in low HIV prevalence population, and to compare the results with new smear positive cases in the same population. DESIGN: It was a retrospective record based study. All patients registered between January 1999 and June 2005 were divided into new smear positive and new smear negative groups and the difference in the outcomes analysed. RESULTS: Favourable outcome was less in new smear negative cases, compared to new smear positive (84% vs. 86%, p = 0.002).Death and default were more in new smear negative cases, compared to new smear positive (death: 6.8% vs. 3.7%; DEFAULT: 6.02% vs. 4.18%), (p < 0.05). Failure and transferred out were non significantly higher in new smear positive group. CONCLUSIONS: Smear negative patients had a worse treatment outcome compared to smear positive patients including lower favourable outcomes and higher deaths and defaults. The possible reasons need to be explored and corrective actions need to be taken accordingly. PMID- 20349757 TI - Sternal tuberculous osteomyelitis presenting as a pulsatile swelling. AB - Primary sternal tuberculous osteomyelitis is a rare form of tuberculous osteomyelitis. We report a case of a young adult with primary tuberculous osteomyelitis of the sternum who presented with a pulsatile anterior chest wall swelling. Computed tomography of the thorax revealed a hypodense lytic lesion in the body of the sternum that had eroded into the anterior mediastinum where it lay in close contact with the right ventricle, resulting in the clinically evident transmitted pulsations. Among the protean manifestations of tuberculosis this case illustrates a unique presentation as a pulsatile chest wall mass. PMID- 20349758 TI - Primary multi-drug resistant tubercular lymphadenitis in an HIV infected patient. AB - Cervical lymphadenitis is a common extra-pulmonary manifestation of tuberculosis in HIV patient; nevertheless, it seems that the primary Multi Drug Resistant (MDR) involving extra-pulmonary site is uncommon. We report a case of tubercular lymphadenitis by multi-drug resistant strain of Mycobacterium tuberculosis in an HIV seropositive male, which has not been reported so far in literature. PMID- 20349759 TI - Tuberculosis of the middle ear with post auricular abscess. AB - A case of tuberculous otitis media with post auricular abscess is being described in a 14-year-old female patient in view of its rare occurrence. The diagnosis was made on demonstration of acid fast bacilli (AFB) in the ear discharge and characteristic cytological features of post auricular abscess aspirate. PMID- 20349760 TI - Thank you to our supplier colleagues. Corporate relationships benefit both ACHE affiliates and suppliers. PMID- 20349761 TI - Interview with ACHE's 2010-2011 chairman. Interview by Jessica D Squazzo. PMID- 20349762 TI - The new quality-cost imperative: systemwide improvements can yield financial gains. PMID- 20349763 TI - Lean Six Sigma and patient safety: a recipe for success. PMID- 20349764 TI - Boundary issues in rural America. Overlapping relationships create ethical challenges for rural healthcare professionals. PMID- 20349765 TI - Addressing stress and beating burnout. Engaging staff in stress reduction leads to a more productive culture, greater patient satisfaction. PMID- 20349766 TI - Bringing cancer treatment to a community near you. National Cancer Institute delivers high-quality care to rural, underserved areas. PMID- 20349767 TI - Healthcare reform and comparative effectiveness research. New approach targeted to be more efficient and cost effective. PMID- 20349768 TI - Lifelong learning. Are you really up to date? PMID- 20349769 TI - Enhancing quality oversight. Study findings show hospital boards increasingly focused on quality initiatives. PMID- 20349770 TI - Nursing's role in transforming healthcare. Nurses are crucial to closing quality of-care gaps. PMID- 20349771 TI - The CEO's role in physician recruiting. Efforts must be driven from the top. PMID- 20349772 TI - Adopting a systematic approach to bringing healthcare executives into a new position or organization. PMID- 20349773 TI - Referral and ascertainment bias in patients with synchronous and metachronous endometrial malignancy. AB - The purpose of this study was to evaluate the frequency in patients with endometrial cancer of other malignancies and the influence of referral and ascertainment biases on these associations. Analysis of 1,028 local and referred patients who had a hysterectomy for endometrial cancer was based on residence at the time of diagnosis. Altogether, 208 patients had a history of another malignancy, most frequently breast, colon, and ovary. At the time of surgery for endometrial cancer, the prevalence of lymphoma and breast and ovarian cancers was greater than expected although the higher prevalence of lymphoma was limited to referred patients. During follow-up after hysterectomy, the incidence of lung cancer was lower than expected, whereas the incidence of lymphoma was higher. Breast, colorectal, and bladder cancers were more common than expected although this finding was limited to local patients. We concluded that results of epidemiologic studies from tertiary care centers may be misleading if they do not account for referral and ascertainment biases. PMID- 20349774 TI - Impact of three-dimensional (3D) ultrasonography and power Doppler angiography in the management of cervical cancer. AB - PURPOSE: To evaluate the potential role of three-dimensional (3D) ultrasound, and to assess its diagnostic performance and ability to predict therapeutic efficacy in cervical cancer. METHODS: Thirty patients with cervical cancer and 35 normal controls were studied by transvaginal 3D power Doppler ultrasound before treatment. Eleven patients who received neoadjuvant chemotherapy (n = 6), radiation (n = 3), or chemoradiation (n = 2), had further measurements taken one month and two months after treatment. RESULTS: From the receiving operating characteristics curve analysis, the best vascularization index (VI) cutoff value of 5.24 distinguished cervical cancer from the normal cervix, with a sensitivity of 73.3% and a specificity of 94.3%. Cervical tumor volume measured by magnetic resonance imaging was positively correlated with the tumor volume measured by 3D ultrasonography (r = 0.91, p < 0.0001). In six patients who received neoadjuvant chemotherapy, the percent change in tumor volume during the second month of treatment was positively correlated with the percent change in flow index (FI) during the first month of treatment (r = 0.83, p < 0.05). CONCLUSIONS: VI may be a diagnostic marker and FI may be a predictive marker of treatment response in cervical cancer. PMID- 20349776 TI - Shoulder mobility after axillary sentinel node biopsy for early infiltrating breast cancer treatment. AB - It is known that complete axillary lymph node dissection for breast cancer treatment causes more frequent sensitive and motor alterations in the homolateral shoulder and upper limb than sentinel lymph node (SLN) biopsy. However, it is not clear how often patients treated by SLN biopsy suffer from shoulder mobility (SM) restriction, as well as its severity and duration. This study was done aiming to evaluate SM in 38 patients with early infiltrating breast cancer treated by SLN biopsy in whom shoulder movements were assessed before surgery and repeated at one, two and three months later. Shoulder-arm mobility was evaluated by goniometry considering flexion, abduction, aduction, extension, internal rotation and external rotation. An abnormal result for each movement was defined by restriction greater than ten degrees compared to preoperative findings. Significant abnormal results for flexion and abduction were found in all of the patients at the first month evaluation. At the third month assessment no women showed any kind of SM impairment. The average restriction evolution for each of the parameters is presented. It is concluded that there is frequently a slight and transient SM limitation in patients undergoing SLN biopsy. Early postoperative physiotherapeutical assistance should thus be advisable to relieve and shorten disability symptomatology. PMID- 20349775 TI - Out-of-protocol concurrent use of cisplatin and radiation therapy in locally advanced cervical cancer: feasibility and survival. AB - PURPOSE OF INVESTIGATION: We assessed the feasibility, response rates, and overall survival of patients with locally advanced cervical cancer treated with cisplatin-based chemotherapy during radiation therapy on an out-of-protocol basis. METHODS: Sixty-nine consecutive newly diagnosed untreated patients with locally advanced cervical cancer who received chemoradiation between 1999 and 2003 were retrospectively reviewed. Treatment consisted in external beam radiation followed by one 137-cessium intracavitary application. Cisplatin was administered for six weeks during external beam radiation. RESULTS: Treatment was well tolerated, although 52 patients presented some degree of acute adverse toxicity (gastrointestinal 65%, hematological 48%, genitourinary 10%). The 3-year survival rate was 61.8% (95% CI 54.5-69.0), with a mean 41.8 months (95% CI 35.7 48.3). Overall survival after adjusting by FIGO Stage IB2-IIA and IIB-IVA was 73.9% and 50%, respectively (p = 0.1839). Overall survival according to Stages IB2-IIb and III-IVA was 74.8% and 34.9%, respectively (P = 0.0376). CONCLUSION: In patients with locally advanced cervical cancer, adding a weekly regimen of cisplatin to standard pelvic radiation in an out-of-protocol basis is feasible, effective, and showed no unexpected toxicity. PMID- 20349777 TI - The significance of HPV in the follow-up period after treatment for CIN. AB - PURPOSE OF INVESTIGATION: High-risk anogenital human papillomavirus (HPV) infections are causally related to cervical cancer. Successful treatment of cervical intraepithelial neoplasia (CIN) results in complete eradication of HPV in most cases. There is an increasing interest regarding the role of HPV testing in the follow-up period after treatment for CIN. PATIENTS AND METHODS: This retrospective study includes 107 women who underwent conization for histologically verified CIN. All of them had HPV testing pre- and postoperatively. HPV testing was carried out using a hybrid capture assay (HC2). The mean follow-up period was 21.4 months (range 2-76 months). The data were analyzed with respect to success of conization, HPV persistence/recurrence and CIN recurrence. Sensitivity, specificity and negative predictive value (NPV) of HPV testing were assessed and compared to the cytological results. RESULTS: Preoperatively, 97 of 107 women were HPV positive. Ninety-seven conizations showed negative resection margins with 86 women becoming HPV negative. In the following months, nine of these HPV negative women became HPV positive again. Out of ten conizations with positive resection margins, six women became HPV negative. Recurrent CIN 2/3 lesions were observed in 11 women, nine of whom had persistent positive HPV testing throughout the entire study period. Regarding CIN recurrence HPV testing showed a sensitivity of 93%, a specificity of 85% and a NPV of 99%. CONCLUSIONS: The sensitivity of HPV testing concerning persistent or recurrent CIN as well as the NPV are high. The present data suggest that HPV testing should be integrated in a follow-up algorithm after treatment for CIN by conization. PMID- 20349778 TI - Possible role of palliative surgery for bowel obstruction in advanced ovarian cancer patients. AB - OBJECTIVES: Bowel obstruction is a relatively common event (30-40%) in advanced or recurrent ovarian cancer patients. No definitive data are available on the optimal management of this serious complication and treatment is generally limited to adoption of palliative measures. These modalities include both surgical and medical procedures. The aim of this study was to define selection criteria for subjects who would benefit from palliative surgery. STUDY DESIGN: Out of 270 epithelial ovarian cancer patients treated in the period 1984-2005, 75 (28%) developed bowel obstruction related to progression/recurrence of the disease. Palliative treatment - both medical and surgical - was applied on an individual basis. A new score developed by these authors was retrospectivelly applied to this group of patients with the aim of defining a subgroup that could benefit from surgical treatment. RESULTS: Fifty cases (66.7%) were medically treated whereas 25 patients (33.3%) underwent surgery. Mean and median survival rates were 34 and 28 weeks in the surgical group versus 12 and four weeks in the medical group. Distribution according to score showed 53 cases (71%) in the low score group (< 14) and 22 (29%) in the high score group (> 14). A significantly better survival was observed in the low-score group (p < 0.0001) and in the surgically treated patients (p < 0.001). According to the risk score variables patients treated surgically for obstruction with low scores had a longer survival (p < 0.005) compared to medical treatment but this difference was not found in the high-risk group (p < 0.05). CONCLUSIONS: The prognosis of patients with bowel obstruction in relation to advanced ovarian cancer is best determined by comprehensive assessment of all prognostic parameters to define a subgroup of patients in a low-risk group that may benefit from surgical treatment. PMID- 20349779 TI - The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4,975 cases in Japan. AB - OBJECTIVE: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. METHODS: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. RESULTS: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. CONCLUSION: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease. PMID- 20349780 TI - Prediction of suboptimal cytoreduction of epithelial ovarian carcinoma by preoperative computed tomography. AB - In an aim to evaluate the diagnostic efficacy of preoperative abdominal-pelvic CT for the prediction of suboptimal cytoreduction of epithelial ovarian carcinoma (EOC) at primary surgery, CT scans of 48 patients who underwent primary surgery for EOC were retrospectively analyzed. The presence of at least one of the following CT findings: multiple implants > 1 cm in maximum diameter in the mesenteria of the small or large intestines, porta hepatis or intersegmental fissure or on the hepatic surface, diaphragmatic peritoneum, gastrohepatic or gastrosplenic ligaments or the extension of tumor infiltration > 2 cm on the omentum towards the spleen or stomach or the intestines encased by the tumor > 2 cm, diffuse peritoneal thickening or invasion of the lateral pelvic wall > 1 cm or multiple lymph nodes > 1 cm at the cardiophrenic and suprarenal levels were accepted as the critical markers for predicting suboptimal cytoreduction. Suboptimal surgery, defined as leaving a residual tumor mass > 1 cm, was determined in 18 (37.5%) patients. CT predicted suboptimal cytoreduction with 83.3% (15/18) sensitivity, 90% (27/30) specificity and 87.5% (42/48) accuracy. PPV and NPV values were 83.3% (15/18) and 90% (27/30), respectively. These results suggested that preoperative CT could successfully predict suboptimal surgery in patients with EOC. PMID- 20349781 TI - Analysis of odds ratio of increased relative risk of developing breast cancer in different groups of women. AB - Taking into account the large number and variety of factors of breast cancer there is constant need and necessity to monitor the risk of developing the disease. It is important to take preventive actions--health education concerning lifestyle and possible ways to modify unhealthy aspects. Quantitive assessment of risk of developing invasive breast carcinoma can be performed using the Gail model (GM). This method is designed to estimate relative and cumulative risk during the entire lifetime or at a certain age of a patient, considering risk factors. It is possible to identify women with increased risk of breast carcinoma and to choose a proper diagnostic path. The purpose of this study was to estimate the relative risk (RR) and to analyze the odds ratio (OR) of increased risk of developing breast cancer. The participants in the study were healthy women with no focal changes in mammary glands and women with diagnosed malignant or benign breast neoplasms. The total number of participants was 555 females aged 35-70 years. The study was carried on in the Great Poland and Lubuskie provinces between 2005 and 2006. High 5-year relative risk of developing breast cancer assessed by the Gail method, proved that this method was a useful tool in confronting reality. In classification of women to a group of increased risk of breast carcinoma, apart from assessment by the Gail method, factors like: BMI, education, medical interventions in puerperium and number of cases of familial invasive cancers should be taken into account. PMID- 20349782 TI - Analysis of protein profiles in human epithelial ovarian cancer tissues by proteomic technology. AB - BACKGROUND: Screening in ovarian cancer is progressively finding out candidate genes and proteins which may work as screening biomarkers and play a role in tumor progression. We examined the protein expression patterns of ovarian cancer tissues using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of fight mass spectrometry (MALDI-TOF MS). METHODS: Tissues from 36 ovarian cancers and 20 normal ovaries were examined by 2 DE. The images of silver stained gels were analyzed by ImageMaster 2D Elite. The peptide mixtures, after in-gel digestion, were determined by MALDI-TOF MS for fingerprinting. The de-isotope tryptic peptide profiles were matched by using the Mascot search engine based on the entire NCBI and Swiss-Prot protein databases. Western/dot blots were then applied to verify the findings. RESULTS: In ovarian cancer, 12 proteins that showed differential expressions were identified unequivocally. Among these proteins, five proteins (galectin-1, cathepsin B, ubiquitin carboxy-terminal hydrolase L1, HLA class II antigen DRB1-11 and heat shock protein 27) were up-regulated and seven proteins (cellular retinol-binding protein, transthyretin, SH3 binding glutamic-rich-like protein, tubulin-specific chaperone A, DJ-1, gamma-actin and tropomyosin 4) were down-regulated. CONCLUSION: The present study is the first to report the up-regulation of ubiquitin carboxy-terminal hydrolase L1 and the down-regulation of SH3 binding glutamic-rich-like protein, tubulin-specific chaperone A, and tropomyosin 4 in human ovarian cancer tissues. Further cloning and functional analysis of these salient proteins will provide more information on their pathophysiologic roles in ovarian cancer. PMID- 20349783 TI - Mesothelin gene expression and promoter methylation/hypomethylation in gynecological tumors. AB - PURPOSE: Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. In this study, we investigated the methylation/hypomethylation status in the promoter region of the mesothelin gene in gynecological tumors. METHODS: Forty-four ovarian tumor specimens and 16 cases of uterine endometrial carcinoma, and normal tissue specimens were used. Monoclonal antibody (5B2) was employed for the immunohistochemical analysis. The methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) technique was used to quantify the methylation/hypomethylation status at 20 CpG sites in the mesothelin promoter region. RESULTS: Mesothelin was expressed in 100% of serous cystadenocarcinoma and 100% of serous borderline tumor of the ovary. None of the germ cell tumors and sexcord-stromal tumors was immunoreactive. Fifty percent of endometrial carcinoma was immunoreactive for mesothelin. The average methylation of CpG sites in ovarian tumors ranged from 6-56% (median: 31%) in mesothelin-positive and 13 79% (median: 43%) in mesothelin-negative samples. In endometrial tumors, the average methylation ranged from 5-52% (median: 28%) in mesothlin-positive and from 15-67% (median: 22%) in mesothlin-negative samples. A correlation was found between mesothelin expression and the average methylation/hypomethylation status as well as methylation/hypomethylation status at four of 20 CpG sites in ovarian samples. No correlation was found in endometrial samples. CONCLUSION: We detected diverse levels of methylation/hypomethylation at CpG sites in the mesothelin promoter region in ovarian and endometrial tumors. We speculate that, although methylation/hypomethylation changes may affect its transcription, other mechanisms may synergically operate in tissue-specific expression and tumor related mesothelin overexpression. PMID- 20349784 TI - Prevalence of human papilloma virus infection in pregnant Turkish women compared with non-pregnant women. AB - PURPOSE OF INVESTIGATION: We aimed to find a prevalence of human papilloma virus (HPV) in order to define the 100 genotypes and subset of 14 oncogenic genotypes in pregnant Turkish women and to compare these with non-pregnant women. METHODS: Cervical thin-prep specimens were obtained from 164 women in the first trimester pregnancy and 153 non pregnant women. RESULTS: 29.2% of pregnant versus 19.6% of non-pregnant Turkish women had at least one of the 100 types of HPV infection--a statistically significant difference. The rate of 14 high-risk HPV genotype infections was significantly higher in pregnant (14.6) compared to non-pregnant Turkish women (9.6%). CONCLUSIONS: Pregnant Turkish women are at higher risk for all HPV infections including high-risk cervical cancer genotypes. PMID- 20349785 TI - Analysis of the cytogenetic response in peripheral blood lymphocytes from breast cancer patients following chemotherapy. AB - The presence of chromosomal aberrations induced in circulating lymphocytes from breast cancer patients during chemotherapy was analyzed. Ten breast cancer patients undergoing neoadjuvant chemotherapy and ten healthy women (controls) were evaluated. Metaphases were obtained from cultures of peripheral lymphocytes stimulated with phytohemaglutinin and metaphase blockage was achieved with colchicine. One hundred metaphases were analyzed for chromosomal aberrations and 1,000 cells for the mitotic index. No significant differences were observed regarding the frequency of chromosomal aberrations, number of cells with chromosomal aberrations and mitotic index between the controls and patients before chemotherapy. However, after the first chemotherapy cycle, the numbers of chromosomal aberrations and cells with them was greater. After the third cycle, the mitotic index was lower, but the fifth cycle produced an increase in relation to the third and fourth cycles. The results suggest that chemotherapy raises the number of chromosomal aberrations and favors persistence of stable chromosomal abnormalities. PMID- 20349786 TI - Is sentinel node biopsy reliable in large breast tumors? AB - PURPOSE: The value of sentinel lymph node biopsy (SNB) in patients with larger breast tumors (diameter > 3 cm) has been questioned due to high false-negative rates reported from initial studies. The aim of this study was to analyze the safety and prognostic reliability of SNB in this group of patients. METHODS: During a 6-year period (2001-2007), 84 women with mean age 51.7 +/- 11.6 years diagnosed with a breast tumor larger than 3 cm in diameter on pathological analysis were retrospectively identified from the database of our institution. Sentinel node identification was performed after injection of blue dye subcutaneously at the subareolar area. The sentinel node specimen was sent for frozen section analysis. Regardless of the SNB results, all patients underwent completion axillary clearance. RESULTS: Breast surgery consisted of mastectomy in 62 patients (73.8%) and partial mastectomy in 22 patients (26.2%). There were 69 invasive ductal cancers (82.1%), 14 lobular cancers (16.6%) and one case of anaplastic carcinoma (1.3%). Nine tumors (10.7%) were identified to be multifocal after the histopathological report. The mean number of sentinel nodes removed was 1.5 +/- 0.7 (range 1-4) while SNB detection was not feasible in three patients (3.6%). Of 56 positive SNBs, seven (12.5%) were not identified by routine hematoxylin and eosin staining during frozen section analysis but were detected by subsequent immunohistochemistry on the final histopathological report. All patients with multifocal tumors presented nodal metastases on pathological analysis (100%), while the rate of nodal metastatic disease in patients with unifocal tumors was 16% (12 patients), although no statistical significance was documented. The overall false-negative rate, defined as the percentage of all node-positive tumors in which the SNB was negative, was 14.3%. The false-negative rate was significantly higher for the group of patients with multifocal tumors (55.5%) compared to the group with unifocal tumors (9.3%) (p < 0.001). CONCLUSIONS: The present study indicates that sentinel node biopsy is feasible in patients with larger breast tumors (max. diameter > 3 cm), with comparable false negative and sentinel detection rates (14.3% and 96.4%, respectively). Larger tumor size seems to be associated with increased incidence of nodal metastases while multifocality appears to be related to increased false-negative rates; hence completion axillary clearance should be initially considered for these cases. PMID- 20349787 TI - Laser vaporization in the management of CIN. AB - AIMS: To evaluate the effectiveness of laser CO2 vaporization in high-grade cervical intraepithelial neoplasias and to assess the diagnostic reliability of cytology, colposcopy, microbiology and HPV tests in predicting recurrence in a long-term outcome. METHODS: Forty-four patients affectd by high-grade cervical intraepithelial neoplasia (HG-CIN) were submitted to laser CO2 vaporization and followed-up a minimum of five years. Vaginal smears for microbiological examination were detected. HPV testing was performed by polymerase chain reaction (PCR). RESULTS: The average age of the patients was 19.5 years (range 15-24). The cure rate after a single treatment was 95%. Two cases (5%) revealed HG-CIN persistence after three months. The five year follow-up of all cases submitted to a second laser procedure revealed negative cytologic and colposcopic findings. CONCLUSIONS: A higher degree of expertise and experience from the colposcopist and long-term follow-up proves the effectiveness of laser vaporization in the management of CIN in young women. It has been suggested that HPV infection alone may not be sufficient to promote carcinogenesis and that other cofactors could be involved. Microbiological tests are important to identify and treat any inflammation which might represent a cofactor of HPV infection in the pathogenesis of cervical dysplasia. Cytocolposcopic long-term follow-up, microbiological and HPV tests can improve regression of disease. PMID- 20349788 TI - Sonographic value in diagnosis of hemorrhagic ovarian cysts. AB - PURPOSE: To investigate the sonographic characteristics of hemorrhagic ovarian cysts (HOC) and to avoid unnecessary surgery. METHODS: 113 cases of suspected HOC underwent sonographic and clinical follow-up for three months. RESULTS: 104 cases were clinically diagnosed with HOC as the masses disappeared naturally. The mean length of the greatest diameter was 5.12 +/- 1.33 cm, and the mean period of disappearance was 3.5 +/- 2.4 weeks. There were four patterns of the image: 21 cases (20.2%) showed a diffused dense echo pattern, 25 cases (24.0%) displayed a mixed pattern, 30 cases (28.8%) expressed a sponge-like pattern and 28 cases (27.0%) exhibited a cystic pattern. Ring blood flow with high velocity and low resistance was detected in 41 cases (40%) and there was no internal blood flow. CONCLUSION: HOC showed characteristic features on sonography, which provided useful information to differentiate HOC from ovarian tumors. PMID- 20349789 TI - E-cadherin expression in estrogen receptor-positive and negative breast carcinomas of postmenopausal women. AB - BACKGROUND: Preservation of E-cadherin expression is usually related to non invasive and well differentiated breast carcinomas. PURPOSE: The aim of this study was to evaluate E-cadherin immunohistochemical expression in estrogen receptor (ER) positive and negative infiltrating ductal breast carcinomas. METHODS: Twenty-three postmenopausal patients with Stage II, operable, infiltrating ductal breast carcinomas were divided into groups A (ER+; n = 13) and B (ER-; n = 10). E-cadherin immunohistochemical expression was assessed semiquantitatively according to membrane staining intensity and classified as negative (< 10% of cells with stained membranes), positive + (10-50% of cells stained) or positive ++ (> 50% of cells stained). Fisher's exact test was used to compare the distribution of staining intensity in the two groups (p < 0.05). RESULTS: In group A (ER+), E-cadherin staining was positive in all cases: + (n = 3; 23%) and ++ (n = 10; 77%) compared to three cases (30%) in group B (ER-), + (n = 2; 20%) and ++ (n = 1; 10%). This difference was statistically significant (p < 0.0005). CONCLUSIONS: The present results indicate that E-cadherin expression loss is significantly associated with ER-negative tumors and therefore with a more aggressive phenotype of invasive ductal breast carcinoma. PMID- 20349790 TI - Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases. AB - PURPOSE: To further study the clinicopathologic and immunohistochemical features of ovarian granulosa cell tumors (GCTs). METHODS: We retrospectively studied all cases of GCTs diagnosed in our laboratory over the last 10-year period. Immunohistochemistry for inhibin, vimentin, cytokeratin, Ki-67 and p53 was performed on archival paraffin blocks. Pathologic and immunohistochemical findings were correlated with the clinical records of the patients. RESULTS: Twenty-one cases (15 of the adult and 6 of the juvenile type) were retrieved. All patients were FIGO Stage I at the time of diagnosis. Recurrent disease was detected in four patients (19%) during a median follow-up of 36 months (range 2 26 years). Pathology revealed a concomitant theca-cell component in three cases, a Sertoli-Leydig component in one case, and a thecoma in one case. Archival tissue material was available in 12 cases. Immunohistochemistry was positive for: beta-inhibin in 12/12 cases (100%), vimentin in 11/12 cases (91.7%), cytokeratin in 3/12 cases (25%), CD34 in 0 cases (0%), and p53 in 2/12 cases (16.7%). The Ki 67 index was < 5% in 12/12 cases (100%). No significant correlations were observed between the pathologic and immunohistochemical parameters examined and the clinical outcome. CONCLUSIONS: Despite the relatively indolent nature and favorable prognosis of most GCTs, late recurrences are not a rare event even in Stage I patients, necessitating a close and long-term follow-up. The identification of novel prognostic markers, in addition to our traditional staging parameters such as clinical staging, is needed in order to more accurately predict probabilities of recurrence in these patients. PMID- 20349791 TI - Uterine involvement in advanced epithelial ovarian cancer. AB - BACKGROUND: With an increasing trend for sparing fertility in gynecologic malignancies, we tried to assess uterine involvement in all stages of epithelial ovarian cancer (EOC) in an evidence-based study. METHOD AND MATERIAL: From September 1999 to September 2005, 177 patients with epithelial ovarian cancer underwent staging laparatomy in the Gynecologic Oncology Department, Vali Asr University Hospital, Tehran, Iran. Staging data from patient files and pathologic reports were analyzed. RESULT: Of the 177 cases with EOC, 26% of patients were in Stage I, 13.6% Stage II, 53.1% Stage III and 7.3% Stage IV. Uterine Involvement was 17.9% with serosal involvement in 25 cases (78.1%) and myometrial involvement in seven cases (21.9%). Of these cases 84.4% were in Stages III or more and all had omental involvement (Stage IIIa 7.4%, Stage IIIb 14.8%, Stage IIIc 63% and Stage IV 14.8%). Only 15.6% cases of normal appearing omentum had uterine tumoral involvement. CONCLUSION: Only eight cases had myometrial involvement out of 177 cases of EOC (all in Stage III). All the eight patients had omental or gross pelvic tumoral involvement. In this study we found that in the absence of gross pelvic or omental involvement in EOC, there is really none or minimal chance of myometrial involvement. Future multicenter studies with more cases will show whether standard hysterectomy by multiple serosal biopsies could be replaced. PMID- 20349792 TI - Primary non-Hodgkins lymphoma of the ovary in the background of human immunodeficiency virus (HIV): a bold and curative approach to treatment. AB - Non-Hodgkins lymphoma of the ovary is a rare disease and there is only one previously documented case arising in a patient with human immunodeficiency virus (HIV). In this report, the authors discuss the management of a case of non Hodgkins Lymphoma of the ovary occurring in a patient with HIV and demonstrate that treatment regimens may be successfully implemented in this immunocompromised population without an increase in adverse effects. PMID- 20349793 TI - High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma--report of two cases. AB - BACKGROUND: Endometrial stromal sarcomas (ESS) are rare uterine tumors with unknown etiological risk factors, but estrogen-dependent growth promotion. CASES: We present two patients with advanced ESS, who had increased levels of p,p-DDE; hexachlorobenzene; PCB 28; PCB 52; PCB 101; PCB 138; PCB 153 and PCB 180 in abdominal adipose tissue. Other xenoestrogens were within expected limits for the non-exposed European population. CONCLUSION: Increased levels of xenoestrogens in patients with ESS may be involved in the pathogenesis of ESS. Chronic exposure to xenoestrogens may be a risk factor for tumor progression. PMID- 20349794 TI - Cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with neuroendocrine tumor of the cervix: a case report and review of the literature. AB - We present a case of the syndrome of inappropriate antidiuretic hormone (SIADH) secondary to cisplatin therapy in a patient with advanced-stage large cell neuroendocrine carcinoma of the cervix. This occurred after the first cycle of cisplatin and then again after the second cycle. Carboplatin was substituted for cisplatin, and there were no further episodes of SIADH. PMID- 20349795 TI - Choroidal melanoma metastasized to the ovary: case report and review of the literature. AB - BACKGROUND: Malignant melanoma metastases to the female genital tract in only 2.5% of cases. Melanoma is characterized by clinical variability and unpredictable biological behavior with long remissions and relapses that develop rapidly. CASE AND REVIEW: A 57-year-old woman was admitted for hypogastric pain and weight loss. She had presented enucleation of the right eye six years before for malignant choroid melanoma. Gynaecological examination revealed enlarged ovaries. Bilateral salpingo-oophorectomy, hysterectomy, and omentectomy were performed. Final pathology diagnosed a choroidal metastatic melanoma (CMM). The patient died seven months later. Only seven cases of CMM have been reported in the literature. Patients affected by CMM ranged in age from 38 to 83 years (median 51.2 years), the time to relapse ranged from 3-25 years (median 51.2 years), the size of the cysts ranged from 4-17 cm (median 9.7 cm) and the survival period ranged from 2-14 months (median 8.1 months). CONCLUSION: Malignant melanoma is misdiagnosed because of lack of discriminatory symptoms, increased tumor markers, characteristic imaging findings and the capacity to mimic other tumors. Today CMM still represents a challenge for gynecologic oncologists. PMID- 20349796 TI - Muscle metastasis of low-grade endometrial carcinoma seven years after diagnosis: a case report. AB - BACKGROUND: Early-stage low-grade endometrial carcinoma has an excellent prognosis. In few cases local relapse and/or distant metastases can occur. We report the muscle as an unusual site of metastasis. CASE: A 69-year-old woman underwent surgery for FIGO Stage IA, grade 1 endometrioid adenocarcinoma of the endometrium. After four years she had local relapse without response to chemoradiation, requiring pelvic exanteration. Three years later she was diagnosed with a deltoid muscle metastasis confirmed histologically and bone metastases. After failing hormone therapy, chemotherapy was administered. She died eight months after diagnosis of the bone and muscle metastases. CONCLUSION: Low-risk endometrial carcinoma can behave like a high-risk group. Furthermore, this report describes, to our knowledge, the first case of endometrial carcinoma muscle metastasis. PMID- 20349797 TI - Pure Sertoli cell tumor. a case report and review of the literature. AB - Pure Sertoli cell tumor (SCT) is a rare sex cord tumor and a subtype of Sertoli Leydig cell tumors according to the WHO Classification. They lack a Leydig cell component and do not contain the immature neoplastic stroma found in the neoplasms of the Sertoli-Leydig cell category. The age of the patients ranges between two and 79 years. Sertoli cell tumors occur in women of reproductive age but a few can also occur in children. The most common clinical presentation when occurring in children is isosexual pseudoprecocity. Women of reproductive age and postmenopausal women frequently present with abdominal pain, swelling and menstrual abnormalities. Occasionally SCTs occur in patients who have Peutz Jeghers syndrome. The tumors are hormone functional in 40-60% of cases. They are often estrogenic, occasionally also androgenic or rarely both. Grossly they are usually yellow to brownish, solid or with several cystic areas. Microscopically they show always almost a tubular growth pattern, but they may also have other growth patterns which can be extensive, making the correct diagnosis difficult. These histologic patterns may result in SCTs mimicking other ovarian tumors. The immunohistochemical panel which usually includes EMA, inhibin, chromogranine, CD99 and calretinin is often helpful in establishing the diagnosis. Most SCTs are Stage I, unilateral, cytologically bland, and clinically benign, but occasional examples are high stage. About 11% of Stage I tumors have worrisome histologic features that may portend an adverse outcome. PMID- 20349798 TI - Immunohistochemical findings in primary fallopian tube cancer. Case report. AB - Primary fallopian tube carcinoma is a rare malignancy, representing about 1% of female genital tract malignancies. We present a case report and compare the medical performance with accessible data from the literature as well as present immunohistochemical analysis of estrogen, progesterone, and proliferative together with basic cytokeratin reactions. We found that immunohistochemical expression of ER-beta was dominant over ER-alpha which encourages further evaluations to be performed on a larger number of samples, especially taking into account the very scant progesterone receptor expression we noted. On the basis of the course of disease under study, etiological problems and the possibility of clinical misdiagnosis have been discussed. The low prevalence rate and lack of clear symptoms of this type of carcinoma makes the final clinical diagnosis almost impossible without an intraoperative histopathological study. Multicenter studies are needed to improve the understanding of possible risk factors. PMID- 20349800 TI - Primary malignant mixed muillerian tumour of the fallopian tube. Report of a case. AB - Malignant mixed mullerian tumour of the fallopian tube is an extremely rare lesion and to date only approximately 50 cases have been reported. The tumour is seldom distinguished preoperatively from other more common lesions or ovarian cancer. We report a case of a 60-year-old woman who presented to our hospital with pelvic pain. There was no clinical evidence of ascites or adenopathy. Ultrasound and abdominal and pelvic computed tomography showed a left adnexal mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. Grossly the left side of the fallopian tube was dilated and the cut surface revealed a solid mass filling the entire lumen. Histological examinations showed a malignant mixed mullerian tumour. The tumor was an admixture of both carcinomatous and sarcomatous elements. The carcinomatous element was composed of well to moderately differentiated squamous cell carcinoma and the sarcomatous component was made up of anaplastic spindle shaped cells with hyperchromatic nuclei. An immunohistochemical study was performed. The patient was admitted to the anticancer hospital for further treatment. The prognosis of a primary malignancy of the fallopian tube is poor and depends more on staging than on histologic type and grade. PMID- 20349799 TI - Good prognosis for primary ovarian pure nongestational choriocarcinoma using the EMA/CO regime. AB - Nongestational choriocarcinoma of the ovary is a rare germ cell tumor with a worse prognosis than gestational choriocarcinoma. In this report we present a case of nongestational chroriocarcinoma where the EMA/CO regime was applied. The clinical features, management, and outcome are discussed. PMID- 20349801 TI - All the right pieces. AB - How a struggling county hospital, a for-profit buyer and a wary community came together. PMID- 20349802 TI - Reducing costs. New approaches to an old problem. AB - Current savings strategies aren't sustainable. Here are new tactics. PMID- 20349803 TI - Readmission policy and prevention. PMID- 20349804 TI - Does it all add up? AB - Flaws in Schedule H community benefit reporting will affect systems. PMID- 20349805 TI - Expanded rapid response program reduces mortality. AB - A rapid response program reduces Emergency department crowding mortality, saves money and improves should be a board priority. staff morale. Here are four reasons why. PMID- 20349806 TI - Are you ready for bundled payments? AB - Demonstration projects reveal how alternatives to today's fee-for-service system would work. PMID- 20349807 TI - Making board meetings strategic. AB - Strategic meetings keep trustees focused on annual goals. PMID- 20349808 TI - Four reasons to confront crowding in the emergency department. AB - Emergency department crowding should be a board priority. Here are four reasons why. PMID- 20349809 TI - A dashboard for medical staff goals. AB - A hospital uses a medical staff dashboard to promote quality improvement. PMID- 20349810 TI - Special issue on ultrasonic imaging and therapy. Guest editorial. PMID- 20349811 TI - A tutorial on ultrasonic physics and imaging techniques. AB - Ultrasound is a widely used modality for both therapy and diagnosis in medicine and biology. Currently, in the field of medical diagnosis, ultrasound is responsible for about one in five of all diagnostic images. The physical characteristics of medical ultrasound, along with its behaviour as it interacts with biological tissues, are described in this tutorial. The role of ultrasound in therapeutic and diagnostic applications is briefly described. In view of the importance of ultrasound as a medical imaging modality, the basic technological building blocks utilized in diagnostic ultrasound scanners are also described. Many of these topics are the subjects of other papers in this special issue where they are dealt with in more detail. PMID- 20349812 TI - Aperture-domain processing and its applications in ultrasound imaging: a review. AB - This paper provides a review of advanced algorithms for ultrasound image formation and signal processing that are based on aperture-domain data (i.e. the data recorded by individual channels prior to beam summation). First aperture domain data are defined and their properties described, then two specific examples of phase-aberration correction and vector velocity estimation are presented. For phase-aberration correction, sidelobe-reduction techniques based on the coherence of the received aperture-domain data were tested with clinical breast data; the mean improvements in the contrast and contrast-to-noise ratios were 6.9 dB and 23.2 per cent, respectively. For flow estimation, a conventional scanner can only estimate the flow velocity parallel to the beam axis. The proposed flow estimation technique uses aperture-domain data for two-dimensional flow-velocity estimation. The experimental results demonstrate that the estimation errors for the proposed technique are 2.18 per cent and 18.11 per cent in the axial and lateral velocity components, respectively. Other applications in which aperture-domain data can be used are also discussed. PMID- 20349813 TI - Tissue non-linearity. AB - The propagation of acoustic waves is a fundamentally non-linear process, and only waves with infinitesimally small amplitudes may be described by linear expressions. In practice, all ultrasound propagation is associated with a progressive distortion in the acoustic waveform and the generation of frequency harmonics. At the frequencies and amplitudes used for medical diagnostic scanning, the waveform distortion can result in the formation of acoustic shocks, excess deposition of energy, and acoustic saturation. These effects occur most strongly when ultrasound propagates within liquids with comparatively low acoustic attenuation, such as water, amniotic fluid, or urine. Attenuation by soft tissues limits but does not extinguish these non-linear effects. Harmonics may be used to create tissue harmonic images. These offer improvements over conventional B-mode images in spatial resolution and, more significantly, in the suppression of acoustic clutter and side-lobe artefacts. The quantity B/A has promise as a parameter for tissue characterization, but methods for imaging B/A have shown only limited success. Standard methods for the prediction of tissue in situ exposure from acoustic measurements in water, whether for regulatory purposes, for safety assessment, or for planning therapeutic regimes, may be in error because of unaccounted non-linear losses. Biological effects mechanisms are altered by finite-amplitude effects. PMID- 20349814 TI - Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy. AB - Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art. PMID- 20349815 TI - Three-dimensional ultrasound imaging. AB - This review is about the development of three-dimensional (3D) ultrasonic medical imaging, how it works, and where its future lies. It assumes knowledge of two dimensional (2D) ultrasound, which is covered elsewhere in this issue. The three main ways in which 3D ultrasound may be acquired are described: the mechanically swept 3D probe, the 2D transducer array that can acquire intrinsically 3D data, and the freehand 3D ultrasound. This provides an appreciation of the constraints implicit in each of these approaches together with their strengths and weaknesses. Then some of the techniques that are used for processing the 3D data and the way this can lead to information of clinical value are discussed. A table is provided to show the range of clinical applications reported in the literature. Finally, the discussion relating to the technology and its clinical applications to explain why 3D ultrasound has been relatively slow to be adopted in routine clinics is drawn together and the issues that will govern its development in the future explored. PMID- 20349816 TI - Ultrasonic microscanning. AB - A detailed review is given of the application of high-frequency ultrasound (HFUS) at frequencies of 20 MHz and above for high-resolution, cross-sectional imaging of biological soft tissue. The state of the art of HFUS imaging systems is discussed with respect to the underlying engineering concepts, system designs, and available transducer technology. Furthermore, the dependency of the spatial resolution on the system's parameters is analysed. Skin imaging, eye imaging, small animal imaging for preclinical research, and intravascular ultrasound in coronary arteries for arteriosclerotic disease diagnostics are presented as examples for the application of HFUS imaging in medical diagnostics. It is shown that, in the frame of the indicated applications, ultrasound in the frequency range 20-100MHz gives a good compromise between the contrary demands for a good spatial resolution and a sufficiently large penetration depth of ultrasound waves into the tissue. Scanning schemes for the imaging of tissue morphology are considered, including spatial compounding as a multidirectional imaging technique. PMID- 20349817 TI - Colour flow and motion imaging. AB - Colour flow imaging (CFI) is an ultrasound imaging technique whereby colour-coded maps of tissue velocity are superimposed on grey-scale pulse-echo images of tissue anatomy. The most widespread use of the method is to image the movement of blood through arteries and veins, but it may also be used to image the motion of solid tissue. The production of velocity information is technically more demanding than the production of the anatomical information, partly because the target of interest is often blood, which backscatters significantly less power than solid tissues, and partly because several transmit-receive cycles are necessary for each velocity estimate. This review first describes the various components of basic CFI systems necessary to generate the velocity information and to combine it with anatomical information. It then describes a number of variations on the basic autocorrelation technique, including cross-correlation based techniques, power Doppler, Doppler tissue imaging, and three-dimensional (3D) Doppler imaging. Finally, a number of limitations of current techniques and some potential solutions are reviewed. PMID- 20349818 TI - Haemodynamics and blood flow measured using ultrasound imaging. AB - Visualization of, and measurements related to, haemodynamic phenomena in arteries may be made using ultrasound systems. Most ultrasound technology relies on simple measurements of blood velocity taken from a single site, such as the peak systolic velocity for assessment of the degree of lumen reduction caused by an arterial stenosis. Real-time two-dimensional (2D) flow field visualization is possible using several methods, such as colour flow, blood flow imaging, and echo particle image velocimetry; these have applications in the examination of the flow field in diseased arteries and in heart chambers. Three-dimensional (3D) and four-dimensional ultrasound systems have been described. These have been used to provide 2D velocity profile data for the estimation of volumetric flow. However, they are limited for haemodynamic evaluation in that they provide only one component of the velocity. The provision of all seven components (three space, three velocity, and one time) is possible using image-guided modelling, in which 3D ultrasound is combined with computational fluid dynamics. This method also allows estimation of turbulence data and of relevant quantities such as the wall shear stress. PMID- 20349819 TI - The assessment of microvascular flow and tissue perfusion using ultrasound imaging. AB - Imaging microvascular flow is of diagnostic value for a wide range of diseases including cancer, inflammation, and cardiovascular disease. The introduction of microbubbles as ultrasound contrast agents offers significant signal enhancement to the otherwise weakly scattered signal from blood in the circulation. Microbubbles provide maximum impedance mismatch, but are not linear scatterers. Their complex response to ultrasound has generated research on both their behaviour and their scattered-signal processing. Nearly 20 years ago signal processing started with simple spectral filtering of harmonics showing contrast enhanced images. More recent pulse encoding techniques have achieved good cancellation of tissue echoes. The good quality contrast-only images enabled ultrasound contrast-imaging applications to be established in microvascular measurements in the liver and the myocardium. The field promises to advance the quantification of microvascular flow kinetics. PMID- 20349820 TI - Photoacoustics, thermoacoustics, and acousto-optics for biomedical imaging. AB - Recently there have been significant advances in developing hybrid techniques combining electromagnetic waves with ultrasound for biomedical imaging, namely photoacoustic, thermoacoustic, and acousto-optic (or ultrasound modulated optical) tomography. All three techniques take advantage of tissue contrast offered by electromagnetic (EM) waves, while achieving good spatial resolution in deeper tissue facilitated by ultrasound. In this review the principles of the three techniques are introduced. A description of existing experimental and image reconstruction techniques is provided. Some recent key developments are highlighted and current issues in each of the areas are discussed. PMID- 20349821 TI - Ultrasound image segmentation and tissue characterization. AB - Ultrasound image segmentation deals with delineating the boundaries of structures, as a step towards semi-automated or fully automated measurement of dimensions or for characterizing tissue regions. Ultrasound tissue characterization (UTC) is driven by knowledge of the physics of ultrasound and its interactions with biological tissue, and has traditionally used signal modelling and analysis to characterize and differentiate between healthy and diseased tissue. Thus, both aim to enhance the capabilities of ultrasound as a quantitative tool in clinical medicine, and the two end goals can be the same, namely to characterize the health of tissue. This article reviews both research topics, and finds that the two fields are becoming more tightly coupled, even though there are key challenges to overcome in each area, influenced by factors such as more open software-based ultrasound system architectures, increased computational power, and advances in imaging transducer design. PMID- 20349822 TI - Lithotripsy. AB - Shock wave lithotripsy (SWL) is the process of fragmentation of renal or ureteric stones by the use of repetitive shock waves generated outside the body and focused onto the stone. Following its introduction in 1980, SWL revolutionized the treatment of kidney stones by offering patients a non-invasive procedure. It is now seen as a mature technology and its use is perceived to be routine. It is noteworthy that, at the time of its introduction, there was a great effort to discover the mechanism(s) by which it works, and the type of sound field that is optimal. Although nearly three decades of subsequent research have increased the knowledge base significantly, the mechanisms are still controversial. Furthermore there is a growing body of evidence that SWL results in injury to the kidney which may have long-term side effects, such as new onset hypertension, although again there is much controversy within the field. Currently, use of lithotripsy is waning, particularly with the advent of minimally invasive ureteroscopic approaches. The goal here is to review the state of the art in SWL and to present the barriers and challenges that need to be addressed for SWL to deliver on its initial promise of a safe, effective, non-invasive treatment for kidney stones. PMID- 20349823 TI - Sonoporation, drug delivery, and gene therapy. AB - Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters such as acoustic pressure, pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles. PMID- 20349824 TI - Ultrasound bioeffects and safety. AB - The main mechanisms by which ultrasound can induce biological effects as it passes through the body are thermal and mechanical in nature. The mechanical effects are primarily related to the presence of gas, whether drawn out of solution by the negative going ultrasound pressure wave (acoustic cavitation), a naturally occurring gas body (such as lung alveoli), or deliberately introduced into the blood stream to increase imaging contrast (microbubble contrast agents). Observed biological effects are discussed in the context of these mechanisms and their relevance to ultrasound safety is discussed. PMID- 20349825 TI - Measurements, phantoms, and standardization. AB - The last 25 years has seen a number of significant developments in the establishment of a measurement infrastructure supporting medical applications of ultrasound. This has allowed manufacturers and users of medical ultrasonic equipment to undertake and compare measurements of key parameters describing the magnitude or strength of the applied ultrasonic field in a meaningful and traceable way: for equipment development, standards compliance, and quality assurance purposes. This paper describes the current state of the art for measurement techniques used to determine the key properties of an ultrasonic field, principally acoustic pressure and acoustic power. Measurement tools and methodologies are described in detail, alongside considerations of how these are likely to develop, shaped by user need. The way that these measurement methods underpin a range of international and national specification standards enabling equipment manufacturers to demonstrate that their equipment is safe and fit for purpose is covered. PMID- 20349826 TI - Perspectives on the modern nitrogen cycle. PMID- 20349827 TI - Terrestrial phosphorus limitation: mechanisms, implications, and nitrogen phosphorus interactions. AB - Nutrient limitation to primary productivity and other biological processes is widespread in terrestrial ecosystems, and nitrogen (N) and phosphorus (P) are the most common limiting elements, both individually and in combination. Mechanisms that drive P limitation, and their interactions with the N cycle, have received less attention than mechanisms causing N limitation. We identify and discuss six mechanisms that could drive P limitation in terrestrial ecosystems. The best known of these is depletion-driven limitation, in which accumulated P losses during long-term soil and ecosystem development contribute to what Walker and Syers termed a "terminal steady state" of profound P depletion and limitation. The other mechanisms are soil barriers that prevent access to P; transactional limitation, in which weathering of P-containing minerals does not keep pace with the supply of other resources; low-P parent materials; P sinks; and anthropogenic changes that increase the supply of other resources (often N) relative to P. We distinguish proximate nutrient limitation (which occurs where additions of a nutrient stimulate biological processes, especially productivity) from ultimate nutrient limitation (where additions of a nutrient can transform ecosystems). Of the mechanisms that drive P limitation, we suggest that depletion, soil barriers, and low-P parent material often cause ultimate limitation because they control the ecosystem mass balance of P. Similarly, demand-independent losses and constraints to N fixation can control the ecosystem-level mass balance of N and cause it to be an ultimate limiting nutrient. PMID- 20349829 TI - Global assessment of nitrogen deposition effects on terrestrial plant diversity: a synthesis. AB - Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions. PMID- 20349828 TI - Linking environmental nutrient enrichment and disease emergence in humans and wildlife. AB - Worldwide increases in human and wildlife diseases have challenged ecologists to understand how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth's ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Along with the obvious direct benefits of nutrient application for food production, anthropogenic inputs of N and P can indirectly affect the abundance of infectious and noninfectious pathogens. The mechanisms underpinning observed correlations, however, and how such patterns vary with disease type, have long remained conjectural. Here, we highlight recent experimental advances to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the interrelated nature of human and wildlife disease emergence, we include a broad range of human and wildlife examples from terrestrial, marine, and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases, and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem, and the degree of enrichment; some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, and the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environment rich with infectious pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles. PMID- 20349830 TI - Use of dynamic soil-vegetation models to assess impacts of nitrogen deposition on plant species composition: an overview. AB - Field observations and experimental data of effects of nitrogen (N) deposition on plant species diversity have been used to derive empirical critical N loads for various ecosystems. The great advantage of such an approach is the inclusion of field evidence, but there are also restrictions, such as the absence of explicit criteria regarding significant effects on the vegetation, and the impossibility to predict future impacts when N deposition changes. Model approaches can account for this. In this paper, we review the possibilities of static and dynamic multispecies models in combination with dynamic soil-vegetation models to (1) predict plant species composition as a function of atmospheric N deposition and (2) calculate critical N loads in relation to a prescribed protection level of the species composition. The similarities between the models are presented, but also several important differences, including the use of different indicators for N and acidity and the prediction of individual plant species vs. plant communities. A summary of the strengths and weaknesses of the various models, including their validation status, is given. Furthermore, examples are given of critical load calculations with the model chains and their comparison with empirical critical N loads. We show that linked biogeochemistry-biodiversity models for N have potential for applications to support European policy to reduce N input, but the definition of damage thresholds for terrestrial biodiversity represents a major challenge. There is also a clear need for further testing and validation of the models against long-term monitoring or long-term experimental data sets and against large-scale survey data. This requires a focused data collection in Europe, combing vegetation descriptions with variables affecting the species diversity, such as soil acidity, nutrient status and water availability. Finally, there is a need for adaptation and upscaling of the models beyond the regions for which dose-response relationships have been parameterized, to make them generally applicable. PMID- 20349831 TI - Nitrogen deposition and its contribution to nutrient inputs to intensively managed agricultural ecosystems. AB - Interest in nitrogen inputs via atmospheric deposition to agricultural ecosystems has increased recently, especially on the North China Plain because of extremely intensive agricultural systems and rapid urbanization in this region. Nitrogen deposition may make a significant contribution to crop N requirements but may also impose a considerable nutrient burden on the environment in general. We quantified total N deposition at two locations, Dongbeiwang near Beijing and Quzhou in Hebei province, over a two-year period from 2005 to 2007 using an 15N tracer method, the integrated total N input (ITNI) system. Total airborne N inputs to a maize wheat rotation system at both locations ranged from 99 to 117 kg N x ha(-1) x yr(-1), with higher N deposition during the maize season (57-66 kg N/ha) than the wheat season (42-51 kg N/ha). Plant available N from deposition for maize and wheat was about 52 kg N x ha(-1) x yr(-1), accounting for 50% of the total N deposition or 31% of total N uptake by the two crop species. In addition, a correction factor was derived for the maize season to adjust values obtained from small pots (0.057 m2) compared with field trays (0.98 m2) because of higher plant density in the pots. The results indicate that atmospheric N deposition is a very important N input and must be taken into account when calculating nutrient budgets in very intensively managed agricultural ecosystems. PMID- 20349832 TI - Narrowing the agronomic yield gap with improved nitrogen use efficiency: a modeling approach. AB - Improving nitrogen use efficiency (NUE) in the major cereals is critical for more sustainable nitrogen use in high-input agriculture, but our understanding of the potential for NUE improvement is limited by a paucity of reliable on-farm measurements. Limited on-farm data suggest that agronomic NUE (AE(N)) is lower and more variable than data from trials conducted at research stations, on which much of our understanding of AE(N) has been built. The purpose of this study was to determine the magnitude and causes of variability in AE(N) across an agricultural region, which we refer to as the achievement distribution of AE(N). The distribution of simulated AE(N) in 80 farmers' fields in an irrigated wheat system in the Yaqui Valley, Mexico, was compared with trials at a local research center (International Wheat and Maize Improvement Center; CIMMYT). An agroecosystem simulation model WNMM was used to understand factors controlling yield, AE(N), gaseous N emissions, and nitrate leaching in the region. Simulated AE(N) in the Yaqui Valley was highly variable, and mean on-farm AE(N) was 44% lower than trials with similar fertilization rates at CIMMYT. Variability in residual N supply was the most important factor determining simulated AE(N). Better split applications of N fertilizer led to almost a doubling of AE(N), increased profit, and reduced N pollution, and even larger improvements were possible with technologies that allow for direct measurement of soil N supply and plant N demand, such as site-specific nitrogen management. PMID- 20349833 TI - Consequences of the cultivation of energy crops for the global nitrogen cycle. AB - In this paper, we assess the global consequences of implementing first- and second-generation bioenergy in the coming five decades, focusing on the nitrogen cycle. We use a climate mitigation scenario from the Organization for Economic Cooperation and Development's (OECD) Environmental Outlook, in which a carbon tax is introduced to stimulate production of biofuels from energy crops. In this scenario, the area of energy crops will increase from 8 Mha in the year 2000 to 270 Mha (14% of total cropland) and producing 5.6 Pg dry matter per year (12% of energy use) in 2050. This production requires an additional annual 19 Tg of N fertilizer in 2050 (15% of total), and this causes a global emission of 0.7 Tg of N2O-N (8% of agricultural emissions), 0.2 Tg NO-N (6%), and 2.2 Tg of NH3-N (5%). In addition, we project that 2.6 Tg of NO3(-)-N will leach from fields under energy crops. The emissions of N2O may be an important term in the greenhouse gas balance of biofuels produced from energy crops. PMID- 20349834 TI - Estimating the effects of excess nutrients on stream invertebrates from observational data. AB - Increased nutrient concentrations in streams and rivers have altered biological structure and function. Manipulative studies have provided insights into different mechanisms by which changes in nutrient concentrations influence aquatic biota, but these studies are limited in spatial scope and in their quantification of nutrient effects on aggregate measures of the invertebrate assemblage. Observational data provide a complementary source of information to manipulative studies, but these data must be analyzed such that the potential effects of spurious correlations are minimized. Propensity scores, a technique developed to analyze human health observational data, are applied here to estimate the effects of increased nutrients on the total taxon richness of stream invertebrates in a large observational data set collected from the western United States. The analysis indicates that increases in nutrient concentration are strongly associated with and cause decreases in invertebrate richness in large, but wadeable, open-canopied streams. These decreases in invertebrate richness were not mediated by periphyton biomass, a commonly proposed mechanism by which nutrients influence invertebrates. In smaller, closed-canopied streams, increases in nutrients were associated with small increases in total richness that were not statistically significant. Using propensity scores can greatly improve the accuracy of insights drawn from observational data by minimizing the potential that factors other than the factor of interest may confound the results. PMID- 20349835 TI - Are forested buffers an effective conservation strategy for riparian fauna? An assessment using meta-analysis. AB - Historically, forested riparian buffers have been created to provide protection for aquatic organisms and aquatic ecosystem functions. Increasingly, new and existing riparian buffers are being used also to meet terrestrial conservation requirements. To test the effectiveness of riparian buffers for conserving terrestrial fauna, we conducted a meta-analysis using published data from 397 comparisons of species abundance in riparian buffers and unharvested (reference) riparian sites. The response of terrestrial species to riparian buffers was not consistent between taxonomic groups; bird and arthropod abundances were significantly greater in buffers relative to unharvested areas, whereas amphibian abundance decreased. Edge-preferring species were more abundant in buffer sites than reference sites, whereas species associated with interior habitat were not significantly different in abundance. The degree of buffer effect on animal abundance was unrelated to buffer width; wider buffers did not result in greater similarity between reference and buffer sites. However, responses to buffer treatment were more variable in buffers <50 m wide, a commonly prescribed width in many management plans. Our results indicate that current buffer prescriptions do not maintain most terrestrial organisms in buffer strips at levels comparable to undisturbed sites. PMID- 20349836 TI - Shifting dominance of riparian Populus and Tamarix along gradients of flow alteration in western North American rivers. AB - Tamarix ramosissima is a naturalized, nonnative plant species which has become widespread along riparian corridors throughout the western United States. We test the hypothesis that the distribution and success of Tamarix result from human modification of river-flow regimes. We conducted a natural experiment in eight ecoregions in arid and semiarid portions of the western United States, measuring Tamarix and native Populus recruitment and abundance at 64 sites along 13 perennial rivers spanning a range of altered flow regimes. We quantified biologically relevant attributes of flow alteration as an integrated measure (the index of flow modification, IFM), which was then used to explain between-site variation in abundance and recruitment of native and nonnative riparian plant species. We found the likelihood of successful recruitment of Tamarix to be highest along unregulated river reaches and to remain high across a gradient of regulated flows. Recruitment probability for Populus, in contrast, was highest under free-flowing conditions and declined abruptly under even slight flow modification (IFM > 0.1). Adult Tamarix was most abundant at intermediate levels of IFM. Populus abundance declined sharply with modest flow regulation (IFM > 0.2) and was not present at the most flow-regulated sites. Dominance of Tamarix was highest along rivers with the most altered flow regimes. At the 16 least regulated sites, Tamarix and Populus were equally abundant. Given observed patterns of Tamarix recruitment and abundance, we infer that Tamarix would likely have naturalized, spread, and established widely in riparian communities in the absence of dam construction, diversions, and flow regulation in western North America. However, Tamarix dominance over native species would likely be less extensive in the absence of human alteration of river-flow regimes. Restoration that combines active mechanical removal of established stands of Tamarix with a program of flow releases conducive to native species establishment and persistence is hypothesized to facilitate the codominance of Populus in reaches where it has become rare. Our findings have implications for planning flow related stream restoration, for developing realistic expectations for yield on investment in prescribed flow releases, and for planning flow-related interventions that might be possible if control and management of invasive plant species along rivers is a goal. PMID- 20349837 TI - Integrating environmental and genetic effects to predict responses of tree populations to climate. AB - Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate. PMID- 20349838 TI - Testing alternative models of climate-mediated extirpations. AB - Biotic responses to climate change will vary among taxa and across latitudes, elevational gradients, and degrees of insularity. However, due to factors such as phenotypic plasticity, ecotypic variation, and evolved tolerance to thermal stress, it remains poorly understood whether losses should be greatest in populations experiencing the greatest climatic change or living in places where the prevailing climate is closest to the edge of the species' bioclimatic envelope (e.g., at the hottest, driest sites). Research on American pikas (Ochotona princeps) in montane areas of the Great Basin during 1994-1999 suggested that 20th-century population extirpations were predicted by a combination of biogeographic, anthropogenic, and especially climatic factors. Surveys during 2005-2007 documented additional extirpations and within-site shifts of pika distributions at remaining sites. To evaluate the evidence in support of alternative hypotheses involving effects of thermal stress on pikas, we placed temperature sensors at 156 locations within pika habitats in the vicinity of 25 sites with historical records of pikas in the Basin. We related these time series of sensor data to data on ambient temperature from weather stations within the Historical Climate Network. We then used these highly correlated relationships, combined with long-term data from the same weather stations, to hindcast temperatures within pika habitats from 1945 through 2006. To explain patterns of loss, we posited three alternative classes of direct thermal stress: (1) acute cold stress (number of days below a threshold temperature); (2) acute heat stress (number of days above a threshold temperature); and (3) chronic heat stress (average summer temperature). Climate change was defined as change in our thermal metrics between two 31-yr periods: 1945-1975 and 1976-2006. We found that patterns of persistence were well predicted by metrics of climate. Our best models suggest some effects of climate change; however, recent and long-term metrics of chronic heat stress and acute cold stress, neither previously recognized as sources of stress for pikas, were some of the best predictors of pika persistence. Results illustrate that extremely rapid distributional shifts can be explained by climatic influences and have implications for conservation topics such as reintroductions and early warning indicators. PMID- 20349839 TI - Understanding long-term primate community dynamics: implications of forest change. AB - Understanding the causes of population declines often involves comprehending a complex set of interactions linking environmental and biotic changes, which in combination overwhelm a population's ability to persist. To understand these relationships, especially for long-lived large mammals, long-term data are required, but rarely available. Here we use 26-36 years of population and habitat data to determine the potential causes of group density changes for five species of primates in Kibale National Park, Uganda, in areas that were disturbed to varying intensities in the late 1960s. We calculated group density from line transect data and quantified changes in habitat structure (cumulative diameter at breast height [dbh] and food availability [cumulative dbh of food trees]) for each primate species, and for one species, we evaluated change in food nutritional quality. We found that mangabeys and black-and-white colobus group density increased, blue monkeys declined, and redtails and red colobus were stable in all areas. For blue monkeys and mangabeys, there were no significant changes in food availability over time, yet their group density changed. For redtails, neither group density measures nor food availability changed over time. For black-and-white colobus, a decrease in food availability over time in the unlogged forest surprisingly coincided with an increase in group density. Finally, while red colobus food availability and quality increased over time in the heavily logged area, their group density was stable in all areas. We suggest that these populations are in nonequilibrium states. If such states occur frequently, it suggests that large protected areas will be required to protect species so that declines in some areas can be compensated for by increases in adjacent areas with different histories. PMID- 20349840 TI - Predicting performance for ecological restoration: a case study using Spartina alterniflora. AB - The success of population-based ecological restoration relies on the growth and reproductive performance of selected donor materials, whether consisting of whole plants or seed. Accurately predicting performance requires an understanding of a variety of underlying processes, particularly gene flow and selection, which can be measured, at least in part, using surrogates such as neutral marker genetic distances and simple latitudinal effects. Here we apply a structural equation modeling approach to understanding and predicting performance in a widespread salt marsh grass, Spartina alterniflora, commonly used for ecological restoration throughout its native range in North America. We collected source materials from throughout this range, consisting of eight clones each from 23 populations, for transplantation to a common garden site in coastal Louisiana and monitored their performance. We modeled performance as a latent process described by multiple indicator variables (e.g., clone diameter, stem number) and estimated direct and indirect influences of geographic and genetic distances on performance. Genetic distances were determined by comparison of neutral molecular markers with those from a local population at the common garden site. Geographic distance metrics included dispersal distance (the minimum distance over water between donor and experimental sites) and latitude. Model results indicate direct effects of genetic distance and latitude on performance variation among the donor sites. Standardized effect strengths indicate that performance was roughly twice as sensitive to variation in genetic distance as to latitudinal variation. Dispersal distance had an indirect influence on performance through effects on genetic distance, indicating a typical pattern of genetic isolation by distance. Latitude also had an indirect effect on genetic distance through its linear relationship with dispersal distance. Three performance indicators had significant loadings on performance alone (mean clone diameter, mean number of stems, mean number of inflorescences), while the performance indicators mean stem height and mean stem width were also influenced by latitude. We suggest that dispersal distance and latitude should provide an adequate means of predicting performance in future S. alterniflora restorations and propose a maximum sampling distance of 300 km (holding latitude constant) to avoid the sampling of inappropriate ecotypes. PMID- 20349841 TI - Long-term recovery patterns of arctic tundra after winter seismic exploration. AB - In response to the increasing global demand for energy, oil exploration and development are expanding into frontier areas of the Arctic, where slow-growing tundra vegetation and the underlying permafrost soils are very sensitive to disturbance. The creation of vehicle trails on the tundra from seismic exploration for oil has accelerated in the past decade, and the cumulative impact represents a geographic footprint that covers a greater extent of Alaska's North Slope tundra than all other direct human impacts combined. Seismic exploration for oil and gas was conducted on the coastal plain of the Arctic National Wildlife Refuge, Alaska, USA, in the winters of 1984 and 1985. This study documents recovery of vegetation and permafrost soils over a two-decade period after vehicle traffic on snow-covered tundra. Paired permanent vegetation plots (disturbed vs. reference) were monitored six times from 1984 to 2002. Data were collected on percent vegetative cover by plant species and on soil and ground ice characteristics. We developed Bayesian hierarchical models, with temporally and spatially autocorrelated errors, to analyze the effects of vegetation type and initial disturbance levels on recovery patterns of the different plant growth forms as well as soil thaw depth. Plant community composition was altered on the trails by species-specific responses to initial disturbance and subsequent changes in substrate. Long-term changes included increased cover of graminoids and decreased cover of evergreen shrubs and mosses. Trails with low levels of initial disturbance usually improved well over time, whereas those with medium to high levels of initial disturbance recovered slowly. Trails on ice-poor, gravel substrates of riparian areas recovered better than those on ice-rich loamy soils of the uplands, even after severe initial damage. Recovery to pre-disturbance communities was not possible where trail subsidence occurred due to thawing of ground ice. Previous studies of disturbance from winter seismic vehicles in the Arctic predicted short-term and mostly aesthetic impacts, but we found that severe impacts to tundra vegetation persisted for two decades after disturbance under some conditions. We recommend management approaches that should be used to prevent persistent tundra damage. PMID- 20349842 TI - Tree cover and biomass increase in a southern African savanna despite growing elephant population. AB - The growing elephant populations in many parts of southern Africa raise concerns of a detrimental loss of trees, resulting in overall reduction of biodiversity and ecosystem functioning. Elephant distribution and density can be steered through artificial waterpoints (AWPs). However, this leaves resident vegetation no relief during dry seasons. We studied how the introduction of eight AWPs in 1996 affected the spatiotemporal tree-structure dynamics in central Chobe National Park, an unfenced savanna area in northern Botswana with a dry-season elephant density of approximately 3.34 individuals per square kilometer. We hypothesized that the impact of these AWPs amplified over time and expanded in space, resulting in a decrease in average tree density, tree height, and canopy volume. We measured height and canopy dimensions of all woody plants around eight artificial and two seasonal waterpoints for 172 plots in 1997, 2000, and 2008. Plots, consisting of 50 x 2 m transects for small trees (0.20-3.00 m tall) nested within 50 x 20 m transects for large trees (> or = 3.0 m tall), were located at 100, 500, 1000, 2000, and 5000 m distance classes. A repeated-measures mixed effect model showed that tree density, cover, and volume had increased over time throughout the area, caused by a combination of an increase of trees in lower size classes and a decrease in larger size classes. Our results indicate that the decrease of large trees can be attributed to a growing elephant population. Decrease or loss of particular tree size classes may have been caused by a loss of browser-preferred species while facilitating the competitiveness of less preferred species. In spite of 12 years of artificial water supply and an annual elephant population growth of 6%, we found no evidence that the eight AWPs had a negative effect on tree biomass or tree structure. The decreasing large-tree component could be a remainder of a depleted but currently restoring elephant population. PMID- 20349843 TI - Linking snake behavior to nest predation in a Midwestern bird community. AB - Nest predators can adversely affect the viability of songbird populations, and their impact is exacerbated in fragmented habitats. Despite substantial research on this predator-prey interaction, however, almost all of the focus has been on the birds rather than their nest predators, thereby limiting our understanding of the factors that bring predators and nests into contact. We used radiotelemetry to document the activity of two snake species (rat snakes, Elaphe obsoleta; racers, Coluber constrictor) known to prey on nests in Midwestern bird communities and simultaneously monitored 300 songbird nests and tested the hypothesis that predation risk should increase for nests when snakes were more active and in edge habitat preferred by both snake species. Predation risk increased when rat snakes were more active, for all nests combined and for two of the six bird species for which we had sufficient nests to allow separate analyses. This result is consistent with rat snakes being more important nest predators than racers. We found no evidence, however, that nests closer to forest edges were at greater risk. These results are generally consistent with the one previous study that investigated rat snakes and nest predation simultaneously. The seemingly paradoxical failure to find higher predation risk in the snakes' preferred habitat (i.e., edge) might be explained by the snakes using edges at least in part for non-foraging activities. We propose that higher nest predation in fragmented habitats (at least that attributable to snakes) results indirectly from edges promoting larger snake populations, rather than from edges directly increasing the risk of nest predation by snakes. If so, the notion of edges per se functioning as ecological "traps" merits further study. PMID- 20349844 TI - Host-adapted parasitoids in biological control: does source matter? AB - It has been hypothesized that the success of a biological control introduction is, in part, dependent on the ability of the control agent to become established in its new environment or to its new population of hosts through local adaptation. Despite this, few studies have investigated the influence of the recent coevolutionary history of pest species and natural enemies on the efficacy of biological control agents, especially for agents that are mass-reared for release in agriculture. We investigate the evolutionary potential of a biological control agent Aphidius ervi to adapt to a key pest species, the foxglove aphid Aulacorthum solani, through components essential to the evolution of parasitoid virulence. We explored (1) the influence of genetic variation from natural source populations on the ability to parasitize natal and non-natal host species; (2) the heritability of key traits related to parasitoid fitness; and (3) the efficacy of parasitoid host-selection lines in a greenhouse system. Source populations maintained genetic variation in the ability to utilize natal and non natal host species; however, only some of the traits sampled suggested local adaptation of parasitoid populations. The ability to parasitize a host was found to be genetically determined and strongly heritable, irrespective of host species. The greenhouse study demonstrated the potential of parasitoid selection lines to substantially increase performance of parasitoids for target pest species. This research provides insight into novel techniques that can be used to increase the quality of biological control agents through the development of lines of natural enemies adapted to particular pest species. PMID- 20349845 TI - Are inland wolf-ungulate systems influenced by marine subsidies of Pacific salmon? AB - Wolves (Canis lupus) in North America are considered obligate predators of ungulates with other food resources playing little role in wolf population dynamics or wolf prey relations. However, spawning Pacific salmon (Oncorhyncus spp.) are common throughout wolf range in northwestern North America and may provide a marine subsidy affecting inland wolf-ungulate food webs far from the coast. We conducted stable-isotope analyses for nitrogen and carbon to evaluate the contribution of salmon to diets of wolves in Denali National Park and Preserve, 1200 river-km from tidewater in interior Alaska, USA. We analyzed bone collagen from 73 wolves equipped with radio collars during 1986-2002 and evaluated estimates of salmon in their diets relative to the availability of salmon and ungulates within their home ranges. We compared wolf densities and ungulate:wolf ratios among regions with differing salmon and ungulate availability to assess subsidizing effects of salmon on these wolf-ungulate systems. Wolves in the northwestern flats of the study area had access to spawning salmon but low ungulate availability and consumed more salmon (17% +/- 7% [mean +/- SD]) than in upland regions, where ungulates were sixfold more abundant and wolves did or did not have salmon spawning areas within their home ranges (8% +/- 6% and 3% +/- 3%, respectively). Wolves were only 17% less abundant on the northwestern flats compared to the remainder of the study area, even though ungulate densities were 78% lower. We estimated that biomass from fall runs of chum (O. keta) and coho (O. kisutch) salmon on the northwestern flats was comparable to the ungulate biomass there, and the contribution of salmon to wolf diets was similar to estimates reported for coastal wolves in southeast Alaska. Given the ubiquitous consumption of salmon by wolves on the northwestern flats and the abundance of salmon there, we conclude that wolf numbers in this region were enhanced by the allochthonous subsidy provided by salmon and discuss implications for wolf-ungulate relations. PMID- 20349846 TI - Propagule pressure and stream characteristics influence introgression: cutthroat and rainbow trout in British Columbia. AB - Hybridization and introgression between introduced and native salmonids threaten the continued persistence of many inland cutthroat trout species. Environmental models have been developed to predict the spread of introgression, but few studies have assessed the role of propagule pressure. We used an extensive set of fish Stocking records and geographic information system (GIS) data to produce a spatially explicit index of potential propagule pressure exerted by introduced rainbow trout in the Upper Kootenay River, British Columbia, Canada. We then used logistic regression and the information-theoretic approach to test the ability of a set of environmental and spatial variables to predict the level of introgression between native westslope cutthroat trout and introduced rainbow trout. Introgression was assessed using between four and seven co-dominant, diagnostic nuclear markers at 45 sites in 31 different streams. The best model for predicting introgression included our GIS propagule pressure index and an environmental variable that accounted for the biogeoclimatic zone of the site (r2=0.62). This model was 1.4 times more likely to explain introgression than the next-best model, which consisted of only the propagule pressure index variable. We created a composite model based on the model-averaged results of the seven top models that included environmental, spatial, and propagule pressure variables. The propagule pressure index had the highest importance weight (0.995) of all variables tested and was negatively related to sites with no introgression. This study used an index of propagule pressure and demonstrated that propagule pressure had the greatest influence on the level of introgression between a native and introduced trout in a human-induced hybrid zone. PMID- 20349847 TI - Probable causes of increasing brucellosis in free-ranging elk of the Greater Yellowstone Ecosystem. AB - While many wildlife species are threatened, some populations have recovered from previous overexploitation, and data linking these population increases with disease dynamics are limited. We present data suggesting that free-ranging elk (Cervus elaphus) are a maintenance host for Brucella abortus in new areas of the Greater Yellowstone Ecosystem (GYE). Brucellosis seroprevalence in free-ranging elk increased from 0-7% in 1991-1992 to 8-20% in 2006-2007 in four of six herd units around the GYE. These levels of brucellosis are comparable to some herd units where elk are artificially aggregated on supplemental feeding grounds. There are several possible mechanisms for this increase that we evaluated using statistical and population modeling approaches. Simulations of an age-structured population model suggest that the observed levels of seroprevalence are unlikely to be sustained by dispersal from supplemental feeding areas with relatively high seroprevalence or an older age structure. Increases in brucellosis seroprevalence and the total elk population size in areas with feeding grounds have not been statistically detectable. Meanwhile, the rate of seroprevalence increase outside the feeding grounds was related to the population size and density of each herd unit. Therefore, the data suggest that enhanced elk-to-elk transmission in free ranging populations may be occurring due to larger winter elk aggregations. Elk populations inside and outside of the GYE that traditionally did not maintain brucellosis may now be at risk due to recent population increases. In particular, some neighboring populations of Montana elk were 5-9 times larger in 2007 than in the 1970s, with some aggregations comparable to the Wyoming feeding-ground populations. Addressing the unintended consequences of these increasing populations is complicated by limited hunter access to private lands, which places many ungulate populations out of administrative control. Agency-landowner hunting access partnerships and the protection of large predators are two management strategies that may be used to target high ungulate densities in private refuges and reduce the current and future burden of disease. PMID- 20349848 TI - Using occupancy models to understand the distribution of an amphibian pathogen, Batrachochytrium dendrobatidis. AB - Batrachochytrium dendrobatidis is a fungal pathogen that is receiving attention around the world for its role in amphibian declines. Study of its occurrence patterns is hampered by false negatives: the failure to detect the pathogen when it is present. Occupancy models are a useful but currently underutilized tool for analyzing detection data when the probability of detecting a species is <1. We use occupancy models to evaluate hypotheses concerning the occurrence and prevalence of B. dendrobatidis and discuss how this application differs from a conventional occupancy approach. We found that the probability of detecting the pathogen, conditional on presence of the pathogen in the anuran population, was related to amphibian development stage, day of the year, elevation, and human activities. Batrachochytrium dendrobatidis was found throughout our study area but was only estimated to occur in 53.4% of 78 populations of native amphibians and 66.4% of 40 populations of nonnative Rana catesbeiana tested. We found little evidence to support any spatial hypotheses concerning the probability that the pathogen occurs in a population, but did find evidence of some taxonomic variation. We discuss the interpretation of occupancy model parameters, when, unlike a conventional occupancy application, the number of potential samples or observations is finite. PMID- 20349850 TI - Assessment of capacity for medical decision making. AB - Determination of a patient's capacity for medical decision making can be simple or complex, depending on the issue being considered; likewise, the degree of capacity required to make decisions varies with the complexity of the situation. A capacity examination is a focused and impartial evaluation of mental status and medical, surgical, psychiatric, and psychosocial histories. The examination is composed of several basic steps, beginning with an assessment of the patient's ability to communicate, followed by determination of his or her understanding of the proposed care, followed by the patient's rationale for decisions about that care. When a patient is deemed to lack capacity, mechanisms should be in place to ensure the patient receives the care needed. This article provides an overview of the concept of capacity, how it is determined, and how to proceed when the patient is found to lack it. PMID- 20349851 TI - Meanings, functions, and experiences of living at home for individuals with dementia at the critical point of relocation. AB - The sociophysical home environment is an integral component of everyday coping, self-identity, and well-being for individuals with dementia; however, residential discontinuity is a common experience for many of these individuals. This article examined the meanings, functions, and experiences associated with living at home for individuals with dementia at the critical point of relocation to a residential care facility. Qualitative research methods were used to analyze in depth interviews with 16 individuals with dementia at their homes within 2 months prior to relocation. At the time of relocation, living at home had become a paradoxical experience for most participants. The findings inform practice and policy interventions at both individual and societal levels to help individuals with dementia age in place for as long as possible and to maximize their efforts to "place" themselves in their new living environments after relocation. PMID- 20349852 TI - Can older adults with dementia accurately report depression using brief forms? Reliability and validity of the Geriatric Depression Scale. AB - The Geriatric Depression Scale (GDS) is a commonly used screening tool, but its use in older adults with cognitive impairment has been controversial. This study compared the short forms of the GDS with clinician diagnosis of depression using standard criteria (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) in people with and without dementia. Sensitivity and specificity were acceptable for all forms of the GDS. These results build evidence for using the short GDS 5- and 15-item versions in populations that include people with mild to moderate dementia, increasing the ease of depression screening so it can be performed more frequently in clinical settings. PMID- 20349853 TI - Travel immunization update for older adults. AB - Older Americans are among the most widely traveled group in our society. Recent trends point to more international travel, more travel to Third World countries, and more travel by older adults with significant health problems. Regardless of the reason for travel, older adults need to plan for healthy travel. Primary care providers need to inquire at routine visits if patients have plans for international travel. If travel to other countries or regions is being considered, patients must be advised of the importance of early travel preparation. To begin with, older adults should be up to date on all routine immunizations. Those planning on international travel may need additional required and/or recommended immunizations, depending on the individual's health status, travel itinerary, length of stay, and health risks associated with destination sites. Primary care providers should be knowledgeable about travel medicine resources in the community to make referrals for travelers requiring additional immunizations and health information. PMID- 20349854 TI - We've got trouble: medications in assisted living. AB - The rise in assisted living facilities (ALFs), coupled with residents with increasingly complex conditions, leads to unanticipated problems linked to medication management. The purpose of this study was to describe one western state's scope of medication-related problems, the relationship of problems to facility characteristics, and the nature of the problems using state surveyors' reports from routine inspections and complaint investigations. Of the 1,335 ALFs surveyed for 2007-2008, 61.8% received a medication-related citation. Of the 1,558 allegations, 60.3% involved individual residents, with 25.2% of these being medication related. The variability in state regulations obscures an accurate understanding of the problem. Complex medication regimens delivered by unlicensed assistive personnel place residents at risk for negative health consequences. More nursing oversight is critically needed to ensure the health and safety of the new generation of ALF residents. PMID- 20349855 TI - Feasibility of Internet training for care staff of residents with dementia: the CARES program. AB - This study evaluated an Internet-based training module, CARES((r)) (Connect with the resident; Assess behavior; Respond appropriately; Evaluate what works; Share with the team), to determine its feasibility for certified nursing assistants (CNAs) in three nursing homes and one assisted living facility. Pre- and posttest questionnaires were administered to 40 CNAs to determine improvements in dementia care knowledge and perceptions of competence in dementia care. Dementia care knowledge improved significantly after CARES training. More than 85% of the sample agreed or strongly agreed that the CARES protocol improved mastery, improved care competency, and reduced stress related to care of residents with dementia. Open-ended feedback indicated that CARES provided CNAs with new information and skills pertaining to dementia care. The results suggest that Internet-based programs such as CARES represent time- and cost-efficient methods to deliver dementia care training in long-term care settings. PMID- 20349856 TI - Topography-Guided vs Wavefront-Optimized Surface Ablation for Myopia Using the WaveLight Platform: A Contralateral Eye Study. AB - PURPOSE: to compare treatments with wavefront-optimized and topography-guided ablations. METHODS: this prospective, randomized, contralateral study comprised 40 eyes (20 patients) with low to moderate myopia with or without astigmatism that underwent topography-guided photorefractive keratectomy (PRK) (ALLEGRO Topolyzer, Alcon Laboratories Inc) in one eye and wavefront-optimized PRK (ALLEGRETTO WAVE software version 2.020 default treatment, Alcon Laboratories Inc) in the fellow eye. Visual acuity, refractive error, contrast sensitivity, and Orbscan (Bausch & Lomb) 3- and 5-mm corneal irregularities were measured preoperatively and 3 and 6 months postoperatively. The results were compared between the two eyes. RESULTS: in both groups, preoperative corrected distance visual acuity (CDVA) (0.03+/-0.09 logMAR for topography-guided and 0.01 +/- 0.06 logMAR for wavefront-optimized [P=.1]), 3-month postoperative uncorrected distance visual acuity (UDVA) (-0.0 1+/- 0.03 logMAR for topography-guided and 0.01 +/- 0.03 logMAR for wavefront-optimized [P=.4]), and 6-month postoperative UDVA (0.01 +/- 0.03 logMAR for topography-guided and 0.0 +/- 0.01 logMAR for wavefront-optimized [P=.3]) were the same. All wavefront-optimized and 18 (90%) topography-guided eyes had UDVA of 20/20 or better. No significant differences were noted between groups in pre- and postoperative spherical and cylindrical refractive errors or corneal irregularity and contrast sensitivity measurements. Six months postoperatively, contrast sensitivity values at 3, 6, 12, and 18 cycles/degree were 5.7 +/- 0.7, 6.0 +/- 1.5, 6.1 +/- 1.3, and 5.5 +/- 1.5, respectively, in the topography-guided group, and 6.2 +/- 0.6, 6.4 +/-1.2, 6.4 +/ 1.1, and 5.8 +/- 1.3, respectively, in the wavefront-optimized group (P=.3, P=.5, P=.4, and P=.6, respectively). CONCLUSIONS: using the WaveLight excimer laser platform for PRK, CDVA and contrast sensitivity outcomes were statistically similar between the wavefront-optimized and topography-guided ablations in eyes with low to moderate myopia with and without astigmatism. PMID- 20349857 TI - Short-term effect of topical brimonidine tartrate on intrastromal corneal pressure in rabbits. AB - PURPOSE: Because topical brimonidine tartrate has been reported to decrease flap adherence in the early postoperative period after LASIK, its effect on the intrastromal corneal pressure (ICP) was evaluated. METHODS: An interventional, prospective, animal study was performed. Intrastromal corneal pressure was recorded for 45 minutes in eight eyes of rabbits treated with topical brimonidine tartrate three times daily for 3 consecutive days (study group); eight contralateral eyes were treated with artificial tears (control group). All measurements were performed by the same, masked investigator. RESULTS: Mean ICP was -4.00 +/- 2.90 mmHg, -6.70 +/- 3.00 mmHg, and -9.00 +/- 4.50 mmHg at 15, 30, and 45 minutes, respectively, in the control group. In the study group (brimonidine-treated eyes), the ICP readings were +2.75 +/- 2.90 mmHg, -2.50 +/- 13.00 mmHg, and -8.50 +/- 5.00 mmHg at the same time points, respectively. The differences in the ICP between both groups were statistically significant at 15 minutes (P = .01), but no significant difference was found at 30 or 45 minutes (P = .20 and P = .80, respectively). CONCLUSIONS: Topical treatment with brimonidine tartrate induces a significant decrease in ICP at 15 minutes. This effect on ICP may explain the decreased corneal flap adherence reported in eyes treated with this drug. PMID- 20349858 TI - Incidence of Nd:YAG capsulotomy after implantation of AcrySof multifocal and monofocal intraocular lenses: a case controlled study. AB - PURPOSE: To compare the frequency of posterior capsulotomies in patients receiving a multifocal or monofocal intraocular lens (IOL) of a similar design following cataract extraction. METHODS: Four hundred seventeen eyes underwent cataract extraction and IOL implantation; 275 eyes received the AcrySof SN6OWF (Alcon Laboratories Inc) one-piece monofocal lens (monofocal group) and 142 eyes received the RESTOR multifocal lens (SN60D3 or SA60D3, Alcon Laboratories Inc) (multifocal group). Surgery was performed by two surgeons at one site. Primary outcome measures were incidence, time of onset, and preoperative corrected distance visual acuity (CDVA) for those patients receiving posterior capsulotomies. RESULTS: After average 22-month postoperative follow-up (range: 2 to 41 months), 22 (15.49%) eyes in the multifocal group underwent posterior capsulotomies compared with 16 (5.82%) eyes in the monofocal group (P = .0014). The main indication for Nd:YAG laser capsulotomy in the multifocal group was complaint of poor quality of vision rather than decreased CDVA. The multifocal group underwent capsulotomies after a mean of 8.8 months (range: 1.7 to 29.2 months), whereas the monofocal group required capsulotomies after a mean of 10.4 months (range: 0.8 to 28.6 months) (P = .559). Mean logMAR CDVA before capsulotomy was 0.113 (range: 0 to 0.6) for the multifocal group and 0.244 (range: 0 to 0.48) for the monofocal group (P = .073). CONCLUSIONS: Use of the RESTOR multifocal IOL in clinical practice may result in more frequent Nd:YAG laser capsulotomies. Reasons for this may include increased visual demands of patients receiving presbyopic-correcting IOLs or complex visual phenomena associated with the interaction of multifocal optics and posterior capsule opacification. PMID- 20349859 TI - Outcome of infected total joint replacement. AB - Numerous protocols are used to treat an infected total joint arthroplasty. We evaluated survival outcomes of patients with infected total joint arthroplasties over 35 years to determine if one treatment is more effective than others.Of 17,561 total joint arthroplasties performed at our facility, 116 (0.66%) were diagnosed with deep infection, 22 of which (18.97%) were hematogenous. Success rates among resection, 1-stage, and 2-stage reimplantation arthroplasty were compared in each joint, as were organism types. After excluding 8 patients (6.9%) who died within 1 year of final treatment and 8 lost to follow-up, 30 hips and 70 knees were studied. Seventeen hips were treated with 2-stage arthroplasty; 70.6% succeeded after the first attempt, and 82.4% succeeded after the second. Fifty one 2-stage knees had 54.9% success after the first attempt and 66.7% success after the second. Five of 5 hips treated with 1-stage arthroplasty succeeded after the first attempt, while 1 of 3 one-stage knees succeeded after the first attempt; none of these 8 joints had a hematogenous infection. No joints requiring a third treatment were successful after the third attempt. There were no differences in survival between different bacteria.Treatment of deep prosthetic joint infection is difficult once the first attempt has failed and becomes more so after failure of the second attempt. Two-stage arthroplasty provides good results in most cases (82% in hips, 67% in knees), but a third attempt does not increase these percentages. The organism type does not significantly affect success in infected joint treatment. PMID- 20349860 TI - Experience with a large-frame, disposable external fixator. AB - External fixation is a temporizing measure that has a long history in the treatment of fractures. Thirty-eight newly designed large-frame external fixators were applied for acute lower-limb fractures and pelvis injuries in a level I trauma center. In 75% of cases, the frames were used for first-stage skeletal stabilization, followed by revision to plates or nails 1 to 2 weeks later. The external fixators remained in place from 4 to 28 days (median, 8 days). The fixator is composed of a low-cost plastic resin and uses modular, disposable components. The montage requires only 2 varieties of clamp, monotube rods, and fixation pins already in-house. The device is lighter than conventional fixators yet equal in rigidity. Cost analysis performed by our institution demonstrated cost savings of 20% to 25% compared to conventional external fixation. The new device is packaged sterilely and does not require autoclaving before application. Patient acceptance of the device was good. There were no complications or disadvantages associated with the use of this lower-cost device. Specifically, there were no pin tract infections, no loss of fixation, and no loosening or disassembly of the devices. PMID- 20349861 TI - The use of implantable bone stimulators in nonunion treatment. AB - Delayed or failure of bone healing in fracture, osteotomy, and arthrodesis patients continues to be a clinical dilemma. Electromagnetic stimulation is 1 modality demonstrated in many studies to aid bone healing; however, relatively few studies depict the use and complications associated with direct current implantable bone stimulators. Over a 9-year period, we studied a consecutive series of 120 adult patients who underwent implantation of a direct current bone stimulator. The goals of this study were to determine the time until healing, the presence of infection, and the need for additional nonunion surgery or salvage procedure following internal bone stimulator placement for nonunion treatment. Of the factors affecting the time until healing, tobacco smoking was a significant factor associated with increased time until healing. Tobacco smoking and duration of nonunion prior to implantable bone stimulator placement were both significant factors in the need for revision nonunion surgery or salvage procedure after implantable bone stimulator placement. Deep soft tissue infection or osteomyelitis was a significant factor predicting prolonged time to healing, subsequent infection following implantable bone stimulator placement, and the need for revision or salvage surgery. With the relative lack of complications directly attributable to electromagnetic implantable bone stimulators, their use may be an effective adjuvant to stable internal fixation and autogenous bone grafting in healing nonunions. However, the use of implantable bone stimulators in patients with nonunion prior to deep soft tissue infection or osteomyelitis exhibited an increased rate of postoperative infection in this study. PMID- 20349862 TI - The use of calcium sulfate impregnated with vancomycin in the treatment of open fractures of long bones: a preliminary study. AB - The purpose of this study was to investigate the effect of calcium sulfate impregnated with vancomycin combined with internal fixation in the treatment of open fractures of long bones. Between October 2007 and January 2008, twenty-eight patients (24 men, 4 women) who sustained open fractures of long bones were enrolled. Mean patient age was 34.5 years (range, 19-57 years). According to the classification system developed by Gustilo and Anderson, there were 15 type II open fractures, 11 type IIIa open fractures, and 2 type IIIc open fractures. All the patients were treated with vancomycin-loaded calcium sulphate and internal fixation. Clinical signs of wound infection were recorded. Postoperative radiographs were used to evaluate the bone healing and absorption process.Twenty six of 28 patients were followed-up successfully, with an average follow-up of 10.5 months (range, 6-16 months). No infection was present in the 26 patients. Exudation from the incision or the drain incision was observed in 2 patients. Bacteria culture was negative and the wound healed with dressing change within 15 days. Bone union was observed in 23 patients, with a mean bone union time of 5.8 months (range, 4-9 months). All the calcium sulfate pellets had completely resorbed in an average of 1.4 months (range, 1-2 months). Our study showed that the combination of internal fixation and calcium sulfate impregnated with vancomycin could decrease the incidence of deep infection without impairment to the bone healing process in the treatment of open fractures of long bones. PMID- 20349863 TI - No superiority of cemented metal-on-metal over metal-on-polyethylene THA in a randomized controlled trial at 10-year follow-up. AB - In a randomized controlled trial, 102 cemented Stanmore 28-mm metal-on-metal total hip arthroplasties (THAs) were compared to 98 metal-on-polyethylene THAs in 195 patients. At a mean follow-up of 10 years, 11 patients (11 hips) were lost to follow-up, 53 patients (55 hips) died, and 6 patients (6 hips) underwent revision. Average age of the surviving patients was 79 years. Harris Hip Scores and Oxford Hip Scores had increased significantly in both groups (P=.000). Ten years postoperatively, mean Harris Hip Score was 86 in the metal-on-metal patients and 87 in the metal-on-polyethylene patients (P=.441); Oxford Hip Scores were 27 and 24, respectively (P=.494). Wear was present in 30 of 52 polyethylene cups. Periprosthetic radiolucencies were seen in 57% of the metal-on-metal patients and in 52% of the metal-on-polyethylene patients (P=.680); they were mainly seen in DeLee & Charnley's zones 1 and 2. Serum cobalt and chromium concentration were higher in the metal-on-metal group (cobalt 1.1, chromium 1.0 vs 0.5 and 0.5 mug/L, respectively; P<.001). Patients with high ion levels (maximum 9.5 and 11 mug/L, respectively) all showed high Harris Hip Scores and few or no periprosthetic radiolucencies, and none were revised. Ten-year survival was 95.5% in the metal-on-metal group (4 revisions) and 96.8% in the metal-on polyethylene group (2 revisions; P=.402). All revisions were indicated for aseptic loosening. One case of aseptic lymphocytic vasculitis-associated lesions and no pseudotumors were observed. The absence of clinical superiority of the cemented metal-on-metal bearing and the concerns over their biological effects have led us to favor the cemented metal-on-polyethylene THA. PMID- 20349864 TI - Minimum five-year follow-up results of single-radius, high-flex posterior stabilized TKA. AB - We studied 75 primary total knee arthroplasties (TKAs) performed using a single radius, high-flex posterior-stabilized insert design with a minimum 5-year follow up to document its implant specific complications and clinical results. Nonprogressive osteolysis was observed at zone 4 of the femoral component in 6 knees (8%) and at zone 1 of the tibial component in 6 knees (8%). However, no complications associated with high flexion designs, such as early aseptic loosening, were observed.Preoperatively, mean Knee Society Knee Score and Knee Society Function Score were 55.1 and 45.5, respectively (range, 10-83 and 20-80, respectively). At last follow-up, mean Knee Society Knee Score and Knee Society Function Score improved to 94.9 and 85.9, respectively (range, 70-100 [P<.0001] and 45-100 [P<.0001], respectively). Mean maximal flexion was 122.1 degrees (range, 90 degrees -140 degrees ) and mean range of motion (ROM) was 110.3 degrees (range, 80 degrees -135 degrees ) preoperatively, and these values improved to 128.9 degrees (range, 110 degrees -150 degrees [P<.0001]) and 127.8 degrees (range, 110 degrees -150 degrees [P<.0001]), respectively, at last follow up. Preoperative ROM was found to be the only factor significantly correlated with postoperative ROM at last follow-up by univariate (P=.0020) and multivariate analysis (P<.0067). Accordingly, clinical results were comparable to previous reports of high-flex implants without implant-specific complications. PMID- 20349866 TI - Morphology of the tibialis anterior muscle and its implications in minimally invasive plate osteosynthesis of tibial fractures. AB - We examined the variation in the origin of the tibialis anterior muscle from the lateral aspect of the tibial shaft and interosseous membrane as well as the variation in the morphology of its musculotendinous junction. Forty cadaveric lower leg specimens (20 right and 20 left) were dissected to reveal the anterior compartment. The origin of the tibialis anterior muscle and its relation to the lateral tibial shaft and interosseous membrane were determined. The position of the musculotendinous junction relative to the medial malleolus was also measured. Tibial length ranged from 29.5 to 45 cm (mean, 36.5+/-3.1 cm). The distal limit of the muscle origin was 5.9 to 20.5 cm (mean, 12.1+/-3.3 cm) from the tip of the medial malleolus. The distance between the musculotendinous junction and the medial malleolus ranged from 1.4 to 10.8 cm (mean, 6.1+/-1.9 cm). The attachment of the muscle belly ends between 15.3 and 31.8 cm (mean, 24.4+/-4.1 cm) distally from the joint line at the knee. There was no statistical correlation between tibial length and muscle morphology.This variation warrants consideration in the percutaneous insertion of screws in the distal end of long plates, as the neurovascular bundle may be injured in patients with a shorter muscle belly. We advocate an open distal approach to protect the neurovascular bundle during insertion of the plate and distal screws. PMID- 20349865 TI - Non-drainage is better than 4-hour clamping drainage in total knee arthroplasty. AB - The role of wound drainage in total knee arthroplasty (TKA) is controversial. The use of drainage was believed to be effective in decreasing hematoma formation, but it inevitably increases bleeding because the tamponade effect of a closed and undrained wound is eliminated. Clamping the drain tube in the first 4 hours after TKA can temporarily recreate a tamponade effect for bleeding control. Previous studies compared the clamping drainage with the conventional drainage method but not with non-drainage. Some current studies have shown that drainage in TKA is not necessary. Thus, we conducted a study to compare the outcomes between the patients with temporarily clamping drainage and without drainage.One hundred consecutive patients undergoing primary TKA were included. Change of hemoglobin, blood transfusion, use of narcotics, postoperative wound dressing, length of hospital stay, and range of motion were recorded. The drain-clamping group demonstrated more postoperative hemoglobin loss and a longer hospital stay, and gained no benefit compared with the non-drain group. Therefore, we concluded that despite clamping for 4 hours after TKA, the drain was still of no use. We would not recommend using a draining system routinely after TKA. PMID- 20349867 TI - Combination of the AO-Magerl and load-sharing classifications for the management of thoracolumbar burst fractures. AB - The AO-Magerl classification is widely accepted for the appropriate management of patients with thoracolumbar burst fractures; however, it fails to assess the ability of the injured spine to withstand compressive loading and cannot predict instrumentation failure after short-segment posterior fixation. The load-sharing classification depends on the degree of comminution and apposition of bony fragments.We retrospectively classified according to both classifications 100 consecutive patients with 1-level thoracolumbar burst fractures treated nonoperatively or operatively within a 7-year period. Sixty neurologically intact patients (60%) were treated nonoperatively, 15 (15%) had short posterior instrumentation, 15 (15%) had short anterior instrumentation, and 10 (10%) had combined short posterior instrumentation and anterior strut grafting. Twenty-five of the 40 (60%) surgically treated patients had neurological impairment on admission. Clinical outcome was assessed using a pain and working ability scale. Mean follow-up was 52 months (range, 24-70 months). Function was satisfactory in 55 (92%) nonoperatively treated patients and in 33 (83%) surgically treated patients. Neurological improvement by American Spinal Injury Association (ASIA) grade was observed in patients with incomplete paraplegia (70% of neurologically impaired patients) who were treated operatively.The combination of AO-Magerl and load-sharing classifications provides for accurate selection of treatment, surgical approach, and length of instrumentation, and can guide the decision for additional anterior surgery. PMID- 20349868 TI - Comparison of radiography and computed tomography in evaluating posterior indirect reduction of spinal canal bone fragment. AB - This article describes a retrospective study of patients who underwent posterior indirect reduction procedures for thoracolumbar burst fractures. The goal of this study was to explore a simple and effective method for evaluating the reduction of spinal canal fragments during posterior indirect reduction procedures.Sixty four burst fractures with retropulsed bone fragments encroaching the spinal canal at the thoracolumbar junction were performed. C-arm fluoroscopy was used to evaluate the spinal canal fragments' reduction. A standard lateral view of the thoracolumbar spine was set up. When a continuous and smooth posterior vertebral body line of the injured vertebrae appeared, similar to below and above the vertebrae, the spinal canal bone fragment was considered to be satisfactorily reduced. The midsagittal diameter of the injured segment was measured on preoperative and postoperative computed tomography (CT) scans. Narrowing of the midsagittal diameter of the injured segment was improved from 41.4%+/-15.9% to 13.7%+/-9.7%. The correction value was 27.6%+/-15.6%. All pre- and postoperative outcome variables had statistical significance (P<.01). Forty-two patients experienced a restored posterior vertebral body line with a continuous and smooth vertical line, indicating that the fragment reduction was satisfactory. Post operative CT showed that the spinal canal compromise was <10% (range, 0%-9.8%; mean, 6.1%+/-2.9%).Continuous and smooth posterior vertebral body line imaging is a simple and effective method to judge the reduction of a bone fragment retropulsed into the spinal canal. It can provide evidence as to whether a laminotomy and pushing the bone fragment are necessary during posterior surgery. PMID- 20349869 TI - Femoral neck fractures: does age influence acute hospital stay, delay to surgery, and acute care costs? AB - The population of Western countries is aging. Previous studies have reported that advancing age does not significantly affect acute inpatient stay in femoral neck fractures. The primary goal of our study was to compare inpatient stay in acute orthopedic wards and time delay to surgery with increasing age in patients with femoral neck fractures. We then looked at the effect of covariates on our outcome measures. Our secondary goal was to identify any additional cost implications for acute care of femoral neck fractures with increasing age.This study describes 3712 patients with femoral neck fractures. The unadjusted mean stay in an acute orthopedic ward increased from 12.4 days in the patients younger than 60 years to 21.4 days in the patients 90 to 99 years (P<.0001). Similarly, unadjusted mean surgical delay increased from 20.7 hours to 39.5 hours (P<.0001). The unadjusted cost increased from $3394 in the patients younger than 60 years to $6235 in the patients 90 to 99 years.As the population ages, the number of femoral neck fractures will increase. Our study demonstrates that age is an independent predictor of increased inpatient stay and surgical delay. It also shows that we need increased resources to tackle femoral neck fractures in the aging population. PMID- 20349870 TI - Surgical treatment of developmental hip dislocation in children aged 1 to 3 years: a mean 18-year, 9-month follow-up study. AB - Forty-six consecutive patients with 57 congenitally dislocated hips were treated with open reduction and femoral or acetabular procedures as indicated. Patient age ranged from 12 to 36 months at the time of surgery. We evaluated the outcome of 38 of the 46 patients (83%) with 47 hips (83%) at a mean follow-up of 18 years, 9 months (range, 13 years, 7 months to 24 years, 7 months) after all patients had reached skeletal maturity.Using Severin's radiographic classification, 24 hips (52%) were rated as class I, 12 (26%) as class II, 8 (17%) as class III, 2 (4%) as class IV, and 0 as class V. The mean Iowa Hip Score was 92 points. One patient had significant abductor weakness and a Trendelenburg gait. The mean leg-length discrepancy was <1 cm. Disturbance in growth of the proximal aspect of the femur occurred in 10 hips (22%).In our experience, open reduction of the congenitally dislocated hip in children aged 1 to 3 years, combined with femoral or acetabular procedures, leads to successful clinical and radiographic results in most cases. These patients have an opportunity for normal hip function during childhood and the potential for a straightforward reconstructive procedure should they develop severe degenerative hip arthrosis. PMID- 20349871 TI - Sex-related outcome differences after arthroscopic shoulder stabilization. AB - Arthroscopic shoulder stabilization using Bankart's repair technique has become a standard intervention in the treatment of traumatic shoulder instability. Nevertheless, knowledge about sex-related differences postoperatively is scarce. The goal of our study was to compare the outcome of men and women after arthroscopic shoulder stabilization. All patients underwent arthroscopic shoulder stabilization due to anterior shoulder instability after traumatic shoulder dislocation. Patients received a standardized questionnaire for evaluating subjective parameters. Subsequently, patients were clinically examined by orthopedic physicians where their Constant-Murley score was raised, and apprehension and sulcus sign tests were conducted. The study included 24 men (mean age, 29.9 years; mean follow-up, 55 months) and 12 women (mean age, 31.8 years; mean follow-up, 62.3 months). Women showed a significantly decreased Constant-Murley score compared to men (P=.045). A positive apprehension test indicating decreased shoulder stability was found more often in women (P=.018). A positive sulcus sign test indicating increased joint laxity was found in 25% of women and only 12.5% of men without reaching statistical significance (P=.378). Compared to men, shoulder function as well as shoulder stability was significantly decreased in women after arthroscopic shoulder stabilization. PMID- 20349872 TI - The effect of seprafilm on adhesion formation and tendon healing after flexor tendon repair in chicken. AB - Adhesion of the tendon, which can occur during healing of tendon repair, is negatively affected by the outcome of surgery. In this experimental study, we sought to prevent adhesion of the tendon, and determined the mechanical stiffness of repair tissue by wrapping sodium hyaluronate and carboxymethylcellulose (Seprafilm; Genzyme, Cambridge, Massachusetts) around the repaired tendon segments. The study group comprised 2 groups of 20 chickens. In group I, the right gastrocnemius tendons of the chickens were cut smoothly, and after tendon and sheath repair, the skin was sutured. In group II, the right gastrocnemius tendons of the chickens were cut, the tendons were repaired, and before skin closure, Seprafilm was wrapped around the repaired tendon segments. Plastic splints were used for holding the chickens' ankles in a neutral position, and they were allowed weight bearing for 8 weeks. In group II, anatomic space between the tendon-sheath and tendon was clear and the tendon-sheath complex was sliding easily around the repaired tendon segment, and this complex was more functional both biomechanically and histologically. Also, the Seprafilm-applied tendons (group II) were observed to be biomechanically more resistant to the tensile forces in group I. Seprafilm is an easily applied interpositional material that can be used safely to prevent adhesion during the tendon healing process. PMID- 20349873 TI - Perioperative complications and prognosis for elderly patients with spinal metastases treated by surgical strategy. AB - The rapidly aging population and improved long-term survival due to advancement of cancer treatment have expanded the role of surgical treatment in elderly patients with metastatic spinal disease. The purpose of this study was to evaluate in elderly patients the perioperative complications and prognosis for metastatic spinal disease. Thirty-two elderly patients (>70 years) who underwent surgical treatment based on Tomita's surgical strategy for spinal metastasis since 1999 were retrospectively reviewed. Mean survival time of 15 patients with 2 to 4 points in surgical strategy was 23.6 months; of 10 patients with 5 to 7 points was 15.2 months; and of 7 patients with 8 to 10 points was 5.2 months. In 5 elderly patients (15.6%), the appropriate surgical choice based on the surgical strategy was not possible due to their preoperative conditions. Perioperative complications encountered were respiratory in 6 patients (18.8%), cardiovascular in 3 (9.4%), and delirium in 4 (12.5%). In the nonelderly 161 patients, respiratory complications occurred in 4 patients (2.5%), cardiovascular in 1 (0.6%), and delirium in 2 (1.2%). Respiratory complications and delirium occurred at a significantly higher frequency in the elderly group. Even for elderly patients, the postoperative prognosis could be predicted by the surgical strategy. However, the optimal surgical procedure may deviate from that predicted by the surgical strategy due to their preoperative conditions and an increased risk for perioperative complications. Despite the increased potential for complications, more radical procedures, such as total en bloc spondylectomy, should not be avoided solely due to advanced patient age. PMID- 20349874 TI - Hip resurfacing as treatment for synovial chondromatosis. AB - Synovial chondromatosis is a rare condition of metaplastic cartilage development in the synovial membrane of joints. These foci can form free bodies and lead to mechanical arthrosis. The precise etiology is unknown. All synovial joints can be affected, with the hip and knee being most common. Patients with synovial chondromatosis are usually in their fifth decade and typically present with mechanical pain and diffuse swelling. Due to its rarity and nonspecific manifestations, diagnosis of synovial chondromatosis is often delayed until significant mechanical damage and arthrosis has occurred.Controversy exists regarding surgical treatment of synovial chondromatosis, especially with regard to the hip. Localized disease can be treated with resection of affected synovium (possibly arthroscopically), whereas patients with generalized disease require complete, open synovectomy. With articular damage, total hip replacement has been advocated along with synovectomy.This article presents a case of a young man with painful hip synovial chondromatosis who was successfully treated with hip resurfacing and synovectomy after failed hip arthroscopy. Hip resurfacing provides the surgeon with the opportunity to address not only local or generalized synovial disease, but articular damage as well. Furthermore, its bone preserving properties make this option attractive in the management of this younger patient population. We feel resurfacing has a role in the surgical treatment of synovial chondromatosis. To our knowledge, this is the first case of hip resurfacing arthroplasty for the definitive treatment of synovial chondromatosis. PMID- 20349875 TI - Endoscopic pubic symphysectomy for reclacitrant osteitis pubis associated with bilateral femoroacetabular impingement. AB - This is the first reported case of the completely endoscopic management of osteitis pubis with pubic symphysectomy. A 31-year-old woman suffered from recalcitrant osteitis pubis that had progressed to an end-stage auto-fused condition. Ossified pubic symphyseal fibrocartilage and adjacent heterotopic bone were endoscopically removed as part of a comprehensive surgery that also involved bilateral arthroscopic surgery for symptomatic femoroacetabular impingement. An innovative dual-portal (anterior and supra-pubic) endoscopic technique is presented along with the rationale for the preservation of the inferior (arcuate) pubic ligament and the posterior pubic ligament. Twelve months following this single-stage surgery, the patient reported high satisfaction with decreased pain, improved function, and resolution of a classic waddling gait. The association of intra-articular hip pathology with osteitis pubis is noted. We believe that this minimally invasive bone-conserving surgery may be useful in the management of recalcitrant osteitis pubis and perhaps find broader application in the outpatient endoscopic treatment of athletes afflicted with this condition. PMID- 20349876 TI - Life-threatening posterior circumflex humeral artery injury secondary to fracture dislocation of the proximal humerus. AB - Proximal humeral fractures account for 4% to 5% of all fractures, and most of these are minimally displaced and less prone to neurovascular injuries. This article presents a case of a 65-year-old man who injured the posterior circumflex humeral artery following a fracture dislocation of the proximal humerus leading to a life-threatening hemorrhagic complication during surgical fixation of the dislocated proximal humeral fracture. Preoperative vital signs were normal. Using the deltopectoral approach, the fracture site was exposed and the dislocated head was extracted. Blood pooled and overflowed the cavity at a brisk pace. Blood pressure dropped from 130/70 mm Hg to 90/45 mm Hg, and preoperative follow-up hemoglobin dropped to 4.8 g/dL. The axillary artery was explored and a ruptured posterior humeral circumflex artery was observed that was later ligated. In view of the damage to 1 of the circumflex humeral branches, primary hemiarthroplasty was performed. This article highlights the possibility of encountering life threatening vascular injuries in highly displaced or dislocated 4-part proximal humeral fractures and the significance of obtaining the angiographic studies early in the course of management in such cases. PMID- 20349877 TI - Closed reduction of a dislocated constrained total hip arthroplasty using a novel technique with a PEG board. AB - This article describes a case of closed reduction of a dislocated total hip arthroplasty (THA) out of a constrained acetabular liner using a novel technique with a peg board secured to the operating table.A 79-year-old woman sustained multiple dislocations after a primary THA. She was converted to a constrained liner and sustained no further dislocations for 5 years. She presented after dislocating her hip while getting out of a chair. The patient was taken to the operating room, placed under general anesthesia, and laid supine on the operating table, to which a peg board had been previously securely attached. A padded perineal post was placed in the patient's groin into the peg board. Under fluoroscopy, in-line traction was applied to the right leg until the femoral head was perched on the acetabular liner. With internal rotation and pressure over the trochanter, the femoral head was reduced.This technique requires less set-up time than using a fracture table. It also securely stabilizes the patient without skilled assistants during longitudinal traction. Moreover, if closed reduction fails, the patient can be rapidly placed in the lateral decubitus position for open reduction or revision arthroplasty. Successful closed reduction of a dislocated constrained liner turns an emergent case into an elective case if revision arthroplasty is indicated. This technique can also be easily used for the more common reductions of dislocated nonconstrained THAs. PMID- 20349878 TI - Arthroscopically Assisted Two-stage Cementation Technique for a Periarticular Knee Lesion. AB - Managing skeletal metastatic disease can be a challenging task for the orthopedic surgeon. In patients who have poor survival prognoses or are poor candidates for extensive reconstructive procedures, management with intralesional curettage and stabilization with bone cement with or without internal fixation to prevent development or propagation of a pathologic fracture may be the best option. The use of bone cement is preferable over the use of bone graft, as it allows for immediate postoperative weight bearing on the affected extremity.This article describes a case where the combined use of arthroscopy and a 2-stage cementation technique may allow preservation of the articular surface and optimization of short-term functional outcome after curettage of a periarticular metastatic lesion in a patient with an end-stage malignancy. We used knee arthroscopy to identify any articular penetration or intra-articular loose bodies after curettage and initial cementation of the periarticular lesion of the distal femur. Arthroscopic evaluation was carried out again after the lesion was packed with cement to identify and remove any loose intra-articular debris. The applicability of this technique is broad, and it can be used in any procedure involving cement packing in a periarticular location. Performed with caution, this technique can be a useful adjunct to surgical management of both malignant and locally aggressive benign bone lesions in periarticular locations. PMID- 20349879 TI - Bilateral quadriceps tendon rupture: a rare finding in a healthy man after minimal trauma. AB - Quadriceps tendon rupture is an uncommon injury; the incidence of simultaneous bilateral quadriceps tendon rupture is extremely rare. Two distinct categories individuals older than 50 years and between 27 and 54 years-have been described. Bilateral quadriceps tendon rupture is more common in patients older than 50 years and is thought to be the result of tendon weakening due to obesity and arteriosclerosis-induced fibrotic changes, or previous injury.In younger individuals, bilateral simultaneous quadriceps rupture is less frequent and has been associated with anabolic steroid use, but more frequently with underlying comorbid medical conditions such as chronic renal failure, hyperparathyroidism, endocrine disorder, gout, diabetes and obesity, which predispose the patients to tendon rupture. Our case report is unique because we report the simultaneous bilateral quadriceps tendon rupture following minor trauma in an otherwise healthy 43-year-old man with no predisposing comorbidity. PMID- 20349880 TI - Distal humeral fracture with associated triceps tendon avulsion in a renal transplant recipient. AB - Although distal humeral fractures are well described in the literature, concomitant distal triceps avulsion has not previously been reported. One population that warrants a high index of suspicion for tendon injury after trauma is patients with renal disease. Clinical tests on such patients may yield equivocal results, and in that setting, magnetic resonance imaging may be useful in the diagnosis of concomitant tendon injury. Postoperative rehabilitation is a challenge considering that the old standard of care for isolated triceps avulsions is several weeks of immobilization and that early motion is recommended for open reduction and internal fixation of distal humeral fractures. More recent literature supports early active-assisted range-of-motion (ROM) elbow exercises after triceps tendon repair, and our case supports those recommendations.A 48 year-old, right-hand-dominant man, who was a living-related kidney transplant recipient 3 years previously, presented with radiographic evidence of an intra articular distal humeral fracture. The patient was rejecting his kidney at the time of injury and was receiving 50 mg of prednisone daily. The patient underwent open reduction and internal fixation of the distal humeral fracture and concomitant triceps repair. Postoperatively, active-assisted and passive ROM elbow exercises were begun. At 3-year follow-up, the patient had 10 degrees to 120 degrees of motion at the elbow, with full supination and pronation. PMID- 20349881 TI - Pediatric trigger thumb in identical twins: congenital or acquired? AB - Pediatric trigger thumb is an uncommon condition with a calculated incidence of 3 per 1000 live births or less. Some reports have suggested a congenital etiology while others could not find a single case of pediatric trigger thumb at birth. This article reports the occurrence of bilateral trigger thumbs in identical twins, age 3 years and 9 months, affecting their thumbs to similar extents, which may suggest a congenital etiology.Congenital etiology for trigger thumb has been proposed for many reasons: occurrence in infants, occurrence in twins, occasional bilaterality, possible presence of triggering at birth, and absence of history of trauma. The occurrence of pediatric trigger thumb in twins has been reported 3 times in the literature; all reported cases were bilateral, as in our case.The mean age at presentation of pediatric trigger thumb is 2 years. The thumb is usually held in a fixed flexion position (mimicking a fracture). Examination usually reveals a palpable nodule in the flexor pollicis longus tendon at the metacarpal joint. This is an important clinical sign. Triggering in children, however, is rare. Macroscopically, there is a nodular thickening of the tendon itself. Pathological changes can be found in the tendon, tendon sheath, or both. A specimen taken from one of the nodules in our case showed degenerative changes while those from both pulleys were normal.Pediatric trigger thumb responds predictably to A1 pulley release, preferably before age 4 years, although milder cases may resolve spontaneously. PMID- 20349883 TI - Nurses' and therapists experiences with occupational musculoskeletal injuries. AB - Occupational musculoskeletal injuries are costly to the health care industry. It is estimated that 12% of nurses leave the profession annually because of back injuries. With the use of grounded theory methodology, 15 nursing personnel and physical therapists were interviewed about their perceptions of occupational musculoskeletal injuries. Analysis of the data identified major themes, including feelings of fear and frustration; chronic issue and part of the job; love of the profession and concerns about continuing in the profession; increased risk of injury; compliant with treatment; negative impact on quality of life; negative feelings about the occupational health department; and educational needs. A theory began to emerge in which health care workers accepted occupational injuries as part of the job and took no action or initiated only minor interventions to prevent work-related injuries. The study indicates a need for education and better communication. PMID- 20349885 TI - Keeping in touch. Cell phone use in people with schizophrenia disorders. AB - There is limited research exploring telephone intervention for psychiatric clients; no studies specific to cell phone use have been conducted. This pilot study examined the feasibility and acceptability of cell phone use in individuals with schizophrenia spectrum disorders (SSDs). Ten outpatients with SSDs were provided with previously activated cell phones for 5 months; trained nurses contacted participants weekly. Seven participants completed the 5-month follow-up period. A minority of participants reported difficulty retrieving messages and answering or charging their phone. These preliminary findings indicate the majority of individuals with SSDs are willing to use this method of communication and are able to do so with few problems. Possible barriers to the use of cell phones with this group include lifestyle factors and poor decision making. Future investigations should examine the use of cell phone access to foster personal safety, gain a sense of connectedness to others, and enhance quality of life. PMID- 20349884 TI - Drug therapies for cognitive impairment and dementia. AB - Drugs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease include acetylcholinesterase inhibitor drugs (tacrine [Cognex(r)], donepezil [Aricept(r)], rivastigmine [Exelon(r), Exelon Patch(r)], and galantamine [Reminyl(r), Razadyne(r)]) and glutamate-modulating drugs (memantine [Namenda(r)]). They do not halt the underlying degenerative process but can slow disease progression. Piracetam is a nonprescription noot ropic drug designated by the FDA as an orphan drug for myoclonic seizures. Clinical trials in a diverse group of patients with age-related dementia or cognitive impairment demonstrated a significant benefit, but the methodology of these studies is poor, and long-term effects are unknown. Other therapies discussed in this article include Ginkgo biloba, a nonprescription natural supplement, and Axona", designated by the FDA as a medical food. PMID- 20349886 TI - Responding to command hallucinations to harm: the unpleasant voices scale and harm command safety protocol. AB - Command hallucinations are relatively common in voice hearers and are taken seriously because of the potential threat to self and others. Many variables mediate the relationship between hearing commands and acting on them. This article describes the implementation of the Harm Command Safety Protocol and the Unpleasant Voices Scale to respond to command hallucinations to harm in the context of the dissemination of a multisite, evidence-based behavioral management course for patients with auditory hallucinations. PMID- 20349887 TI - Caring with comfort rooms. Reducing seclusion and restraint use in psychiatric facilities. AB - The reduction of seclusion and restraint is a national patient safety focus in psychiatric settings. Studies have demonstrated that multisensory or comfort rooms contribute to higher consumer satisfaction and lower rates of seclusion and restraint in general hospitals. As an alternative to the traditionally uncomfortable time-out room, a comfort room was constructed on an acute adult inpatient unit. This space was designed with comfortable furniture, soothing colors, soft lighting, quiet music, and other sensory aids to help reduce unsettled patients' level of stress. The frequency and duration of seclusion and restraint use on the pilot unit was studied before and after implementation of the comfort room. The use of seclusion and restraint was also compared with a similar admission unit without a comfort room. Results supported the hypothesis that the presence of a comfort room significantly reduced seclusion and restraint, and that the use of the comfort room helped reduce patients' stress. PMID- 20349888 TI - Preventing adolescent suicide: a community takes action. AB - Suicide is the third leading cause of death for adolescents and young people in the United States. The etiology of suicide in this population has eluded policy makers, researchers, and communities. Although many suicide prevention programs have been developed and implemented, few are evidence-based in their effectiveness in decreasing suicide rates. In one northern California community, adolescent suicide has risen above the state's average. Two nurses led an effort to develop and implement an innovative grassroots community suicide prevention project targeted at eliminating any further teen suicide. The project consisted of a Teen Resource Card, a community resource brochure targeted at teens, and education for the public and school officials to raise awareness about this issue. This article describes this project for other communities to use as a model. Risk and protective factors are described, and a comprehensive background of adolescent suicide is provided. PMID- 20349889 TI - Drinking games and college students. Part 2: Nursing implications. AB - In Part 1 of this article, published in the February 2010 issue, the problem of drinking game participation by U.S. college students was described. College students may play these games for reasons of peer acceptance and social interaction. Unfortunately, approximately two thirds of U.S. college students participate in this risky binge drinking behavior, from which serious consequences and harms can result. In this article, implications for community and mental health nurses are discussed. Nurses in a variety of settings have unique opportunities to educate, counsel, treat, and refer these students regarding the risks and protections of this behavior. PMID- 20349890 TI - Profile of women in a county jail. AB - The literature about women in prison says little about characteristics of women in local jails. The goal of this study was to better understand the demographics and characteristics of these women to develop responsive programming. A cross sectional survey of 346 women in an urban jail was conducted. Descriptive statistics were generated, and a logistic regression analysis was performed to examine contributors to multiple arrests. Of the 346 women surveyed, 65.3% were incarcerated for minor charges and 58.9% had been incarcerated four or more times. Of those with children, the majority had children younger than 18, and nearly 30% had children younger than 5. Partner abuse and involvement in the juvenile justice system were significantly related to multiple arrests. These findings indicated that many women in jail are caught in a cycle of multiple arrests and violence, with many of their children likewise involved. PMID- 20349892 TI - Decompression "Iridopathy" Following Diode Laser Cycloablation. PMID- 20349891 TI - How neuroplasticity and cognitive reserve protect cognitive functioning. AB - Overall cognitive status can vary across an individual's life span in response to factors that promote either positive or negative neuroplasticity. Positive neuroplasticity refers to he physiological ability of the brain to form and strengthen dendritic connections, produce beneficial morphological changes, and increase cognitive reserve. Negative neuroplasticity refers to the same physiological ability of t he brain to atrophy and weaken dendritic connections, produce detrimental morphological changes, and decrease cognitive reserve. Factors that promote positive neuroplasticity include physical activity, education, social interaction, intellectual pursuits, and cognitive remediation. Factors that promote negative neuroplasticity include poor health, poor sleep hygiene, poor nutrition, substance abuse, and depression and anxiety. Implications for promoting positive neuroplasticity and avoiding negative neuroplasticity across the life span are emphasized to facilitate optimal cognitive health and ensure successful cognitive aging. PMID- 20349893 TI - Indirect Intraoperative Visualization of the Posterior Sclera. AB - Adequate exposure of the sclera during posterior ruptured globe repair remains challenging because the globe traction required for direct visualization of the posterior laceration may result in expulsion of intraocular contents through the scleral wound. The authors describe a new technique for indirect visualization of the posterior sclera that allows for meticulous exploration and repair of posterior globe lacerations, while minimizing the need for globe traction and risk of intraocular content loss. PMID- 20349894 TI - Computed Tomography Exophthalmometry. AB - Exophthalmometry is an important clinical tool used in evaluating many orbital diseases. The authors evaluated whether or not exophthalmometry readings obtained from computed tomography (CT) correlate with traditional Hertel measurements. Patients with orbital disease who had undergone clinical and CT examination were identified, and CT exophthalmometry readings were obtained digitally using a GE PACS radiograph viewing system in 53 orbits (44 thyroid-associated ophthalmopathy and 9 post-trauma). Exophthalmometry data obtained with CT were compared with Hertel readings obtained by an experienced examiner. CT data and clinical data were obtained by separate and masked observers. 46 of 53 CT exophthalmometry measurements were within 2 mm of the value recorded from Hertel testing. The CT metrics, on average, provided exophthalmometry that was 0.03mm shorter than Hertel (95% CI). The intraclass correlation coefficient was 0.95 (95% CI) for the two forms of measurement. The authors conclude that CT exophthalmometry correlates well with Hertel exophthalmometry. PMID- 20349895 TI - Strabismus surgery. PMID- 20349896 TI - Enlarging red swelling below the right eye. What's your diagnosis? Diagnosis: Congenital dacryocystocele with acute dacryocystitis. PMID- 20349897 TI - The management of congenital nasolacrimal duct obstruction: an international perspective. PMID- 20349898 TI - A national survey of the management of congenital nasolacrimal duct obstruction in the United kingdom. AB - PURPOSE: To survey national variation in the management of congenital nasolacrimal duct obstruction, particularly the timing of intervention and the use of nasolacrimal intubation, nasal endoscopy, and assistance from an ear, nose, and throat surgeon at different stages of management. METHODS: A telephone survey was conducted of 100 ophthalmologists in the United Kingdom who were involved in the management of congenital nasolacrimal duct obstruction. A sequential management protocol was established for each, including the nature of procedures, their timing, and the use of nasal endoscopy and ear, nose, and throat surgeons. RESULTS: Of those surveyed, 49% use the dye disappearance test for diagnosis. Eighty-four percent suggest lacrimal sac massage to parents. No surveyed ophthalmologists perform "office" probing or balloon dilation. Seventy four percent perform initial probing after 1 year, with 25% using nasal endoscopy. If symptoms persist, 64.5% (60 of 93) repeat the probing, whereas 35.5% (33 of 93) intubate the lacrimal system. The use of nasal endoscopy increases to 50.5% (47 of 93). By the third intervention, 77.6% (45 of 58) perform lacrimal intubation, with 72.4% (42 of 58) using nasal endoscopy. All opt for dacryocystorhinostomy as the fourth intervention and 28.3% (13 of 46) perform this procedure themselves, whereas 71.7% (33 of 46) refer the patient to another practitioner. In total, 65% (65 of 100) use tubes at some stage of management, 58% (58 of 100) make some use of nasal endoscopy, and 33% (33 of 100) involve ear, nose, and throat surgeons. CONCLUSION: Based on the results of this survey, huge variation exists in the management of congenital nasolacrimal duct obstruction in the United Kingdom. Most ophthalmologists intervene soon after patients reach 1 year of age. The rate of nasal endoscopy increases with successive interventions, especially to aid with nasal intubation, either alone or with the assistance of ear, nose, and throat surgeons. PMID- 20349899 TI - Confluent laser photocoagulation for the treatment of retinopathy of prematurity. AB - PURPOSE: To describe the efficacy, outcomes, and complications of confluent laser technique in a cohort of premature infants with threshold retinopathy of prematurity. Laser photocoagulation has a good treatment outcome in the management of retinopathy of prematurity; however, the number and density of laser spots remains debatable. Laser treatment can be done in a scattered pattern, a near-confluent pattern, or a confluent treatment pattern. METHODS: A retrospective chart review of patients with threshold retinopathy of prematurity treated between 2003 and 2006 was conducted. Confluent laser treatment was applied anterior to the ridge extending to the ora serrata 360 degrees . Rate of progression, frequency of retreatment, postoperative complications, structural outcomes, and refractive error were evaluated. RESULTS: A total of 100 eyes from 51 patients were included. Mean gestational age was 28 weeks (range: 23 to 32 weeks) and mean birth weight was 1,065 g (range: 477 to 1,905 g). Patients had a mean follow-up of 13 months (range: 6 to 50 months). Progression to stage 4 or 5 occurred only in a total of 6 eyes (6%). Postoperative complications included cataract, vitreous hemorrhage, corneal edema, and macular dragging. Mean spherical equivalent at the last follow-up visit was -3.80 diopters (range: 19.00 to+4.00 diopters). CONCLUSION: Patients treated with confluent laser photocoagulation had a low rate of progression to stage 4 or 5 retinopathy of prematurity. Also, the need for additional laser treatment was small, with rates of complications and structural outcomes comparable to previous reports using a nonconfluent laser pattern. PMID- 20349901 TI - Major pediatric ocular trauma in Taiwan. AB - PURPOSE: To investigate major pediatric ocular trauma in Taiwan. METHODS: Retrospective review of medical records of all patients 15 years and younger who were hospitalized with a primary diagnosis of eye injury at National Cheng Kung University Hospital, Taiwan, between June 1988 and May 2006. RESULTS: There were 156 children (156 eyes) 1.1 to 15.0 years (mean+/-standard deviation, 7.1+/-0.3 years; boy: girl ratio: 2.1:1). Objects most often causing penetrating injury were scissors (13.5%), pencils/pens (12.2%), broken eyeglasses/spectacles (7.7%), and knives (6.4%). Most blunt trauma occurred in traffic accidents (5.8%). Most injuries occurred at home, followed by on the street, at school, and at sports venues. Injuries were classified as open globe (71.2%), adnexal only (18.6%), or closed globe (10.3%), and included corneal laceration (40.4%), lens damage (27.6%), hyphema (25.6%), and eyelid laceration (23.7%). Most surgical procedures were primary repair (88.5%) or removal of a damaged lens (22.4%). Additional surgery was performed in 19.9% of cases. After treatment, 56.4% of eyes had corneal opacity/scar and 7.1% became phthitic; 52.6% had good visual outcome, whereas 23.1% had poor final vision. Compared with visual acuity measured on admission, final visual acuity was improved in 76.1%, unchanged in 19.7%, and worse in 4.3%. Predictors of worse outcome were open-globe injury and larger wound size, posterior segment involvement, and presence of an intraocular foreign body. CONCLUSIONS: Most of the children hospitalized for major ocular trauma are younger boys with penetrating injuries suffered at home. Most injuries could have been prevented by increased awareness and reduction of risk factors, and the authors urge better public education for improved safety. PMID- 20349902 TI - Vertical rectus muscle transposition for correcting abduction deficiency in Duane's syndrome type 1 and sixth nerve palsy. AB - PURPOSE: To report the clinical outcome and complications of the Scott Foster procedure for treating abduction deficiency in patients with Duane's syndrome type 1 and sixth nerve palsy. METHODS: A retrospective, interventional case series included 62 consecutive patients (62 eyes: 38 eyes with Duane's syndrome and 24 eyes with sixth nerve palsy) who underwent the Scott Foster procedure for treatment of abduction deficiency. The main outcome measures were deviation, face turn, and abduction deficiency. RESULTS: In patients with sixth nerve palsy, mean distance deviation improved from 44.7+/-7.2 prism diopters (PD) before surgery to 12.5+/-4.0 PD after surgery (P<.05), and in patients with Duane's syndrome type 1, mean distance deviation improved from 31.5+/-4.3 PD preoperatively to 9.2+/ 3.1 PD. Mean near deviation improved from 27.1+/-4.5 PD to 6.2+/-2.5 PD in patients with Duane's syndrome and from 40.3+/-6.2 PD to 13.7+/-3.4 PD in patients with sixth nerve palsy. Mean abduction deficiency improved from -4 to -2 (P<.05) in both groups. Face turn improved significantly after surgery. No patient had an overcorrection. No recurrence was detected. CONCLUSION: The Scott Foster procedure is effective for improving deviation, abduction deficiency, and face turn in patients with Duane's syndrome type 1 and especially in those with sixth nerve palsy. PMID- 20349903 TI - Congenital ptosis and amblyopia. AB - PURPOSE: To investigate the incidence and causes of amblyopia in congenital ptosis. METHODS: The frequency and causes of amblyopia were evaluated in 83 eyes of 72 patients with congenital ptosis. Patient ages ranged between 10 months and 70 years. Amblyopia was defined as best-corrected visual acuity of 0.7 or less. After a complete ophthalmologic examination, the amount of ptosis and levator function was determined and the following amblyogenic factors were identified: ametropia, anisometropia, and strabismus. In cases with no other reason for amblyopia, stimulus deprivation amblyopia due to ptosis was assumed. RESULTS: The amount of ptosis was mild in 5 (6%), moderate in 26 (31%), and severe in 52 (63%) of 83 eyes with congenital ptosis. Strabismus was present in 17 (20%) eyes. Visual acuity could not be determined in 10 of 83 eyes with ptosis in children younger than 4 years. The overall incidence of amblyopia in the remaining 73 eyes was 48%. Of those patients with amblyopia, 54% had refractive errors such as anisometropia or ametropia, 20% had strabismus with or without refractive errors, and 26% had amblyopia solely attributed to ptosis. When all eyes with ptosis were included, the rate of stimulus deprivation amblyopia was 12% and all of these eyes had severe ptosis. CONCLUSION: Early detection and treatment of amblyogenic factors such as refractive errors and strabismus is recommended and, when the pupillary axis is occluded with severe ptotic eyelids, surgery should be performed as soon as possible to prevent stimulus deprivation amblyopia. PMID- 20349904 TI - Diagnosis and pathogenesis of congenital X-linked retinoschisis with optical coherence tomography. AB - This study shows how optical coherence tomography has been valuable in the diagnosis of congenital X-linked retinoschisis. An infant with convergent strabismus underwent serial optical coherence tomography examinations that helped to make the diagnosis of congenital X-linked retinoschisis. Optical coherence tomography is useful in the diagnosis of congenital X-linked retinoschisis and adds new information about pathogenesis. The authors recommend the use of optical coherence tomography in pediatric retinal disease, even if the macula appears normal on indirect ophthalmoscopy. PMID- 20349905 TI - Severe ocular injuries from improperly disposed medical syringes in children. AB - This report describes ocular injuries caused by syringes in children. The records of 12 children injured with syringes were reviewed. There were seven cases of endophthalmitis, two cases of panophthalmitis, one case of retinal detachment, one case of endophthalmitis with retinal detachment, and one case of traumatic cataract. All patients received treatment within 24 hours of presentation. Patients presented an average of 8.4 days after injury. Final visual acuity ranged from no light perception to counting fingers at 90 cm in eight patients and could not be assessed in four patients. Improperly disposed syringes may pose a significant risk for ocular injury and visual loss in children, especially when presentation is delayed. PMID- 20349906 TI - Spontaneous bilateral anterior lens dislocation in an 8-year-old girl. AB - The authors describe recurrent lens dislocation into the anterior chamber in a young girl with homocystinuria. The patient's 12-year-old sister died after a cerebrovascular accident caused by the same disease. This report highlights the importance of early dietary restrictions and treatment. PMID- 20349907 TI - Pediatric ocular rosacea. AB - A case of severe pediatric ocular rosacea was effectively treated after 2.5 years of misdiagnosis. A high index of suspicion should be maintained in children with ocular surface disease, with or without dermatologic rosacea, to correctly diagnose ocular rosacea and avoid morbidity and complications. PMID- 20349908 TI - Bilateral juvenile choroidal neovascularization associated with Best's vitelliform dystrophy: observation versus photodynamic therapy. AB - The authors recently observed a boy with bilateral choroidal neovascularization associated with Best's disease and compared the outcome of photodynamic therapy in one eye with the natural history of the untreated fellow eye. The final outcome of photodynamic therapy was inactive choroidal neovascularization, which seemed to be enveloped by the retinal pigment epithelium. The final appearance of the treated lesion was similar to the natural evolution of choroidal neovascularization in the untreated fellow eye. PMID- 20349909 TI - Bilateral primary congenital glaucoma in monozygotic twins. AB - Primary congenital glaucoma is an uncommon pediatric ocular disease contributing to a disproportionately high percentage of childhood blindness worldwide. This case report describes bilateral primary congenital glaucoma in monozygotic twins who first presented to an ophthalmologist in Ethiopia at 6 years of age. Both had severe, protracted disease, with only moderate improvement after surgical intervention. PMID- 20349910 TI - Haab's striae with congenital glaucoma. PMID- 20349911 TI - Polyphenol-rich extracts from Solanum nigrum attenuated PKC alpha-mediated migration and invasion of hepatocellular carcinoma cells. AB - Solanum nigrum L. (SN) has exhibited multiple biological effects such as anti inflammation and antiproliferation. Protein kinase C (PKC) regulates cellular functions including proliferation, migration, and invasion. In the present investigation, we demonstrated that 12-o-tetradecanoylphobor-13-acetate (TPA) and constitutively activated PKC alpha significantly increased migration and invasion of HepG2 cells, while treatment with water or polyphenol extracts of SN (SNWE or SNPE) attenuated TPA-induced migration and invasion. SNWE and SNPE reduced TPA elicited PKC alpha expression in a dose-dependent manner and obviously inhibited TPA-induced phosphorylation of p38 and ERK, respectively. Constitutively activated PKC alpha (caPKC alpha) significantly reversed the inhibitory effects of SNWE and SNPE on ERK and p38 activation. However, the antimigration effect of SNWE and SNPE could not be abrogated by caPKC alpha. Our results revealed the antimigration and anti-invasion effects of both extracts derived from SN, which may act as a promising therapeutic agent for the treatment of hepatocellular carcinoma. PMID- 20349912 TI - Determinants of urinary deoxynivalenol and de-epoxy deoxynivalenol in male farmers from Normandy, France. AB - Dietary exposure to deoxynivalenol (DON) from contaminated cereal crops is frequent in Europe, and farm workers who handle grain or silage may be at additional risk. In this study we refined a urinary assay for DON and present a novel assay for the DON metabolite de-epoxy-deoxynivalenol (DOM-1). These were applied to a pilot survey of male French farmers (n = 76, aged 23-74). DON was detected in 75/76 samples (range 0.5-28.8 ng/mL) and DOM-1 in 26/76 samples (range 0.2-2.8 ng/mL). In multivariate analysis including creatinine as a covariate, bread consumption, other cereal consumption, and maize acreage contributed to the model, explaining the variation in urinary "DON and DOM-1" concentration combined (R(2) = 0.33). This is the first exposure biomarker survey for DON in a French population, and the first demonstration of urinary DOM-1 in humans. Further investigations into occupational activity, handling, or airborne exposures would be informative. PMID- 20349913 TI - Surface energy and wettability of spin-coated thin films of lignin isolated from wood. AB - The surface energy of lignin films spin-coated onto oxidized silicon wafer has been determined from contact angle measurements of different test liquids with varying polar and dispersive components. Three different lignin raw materials were used, a kraft lignin from softwood, along with milled wood lignin from softwood and hardwood. Infrared and (31)P NMR spectroscopy was used to identify any major functional group differences between the lignin samples. No significant difference in the total solid-vapor surface energy for the different lignin films was observed; however, the polar component for the kraft lignin was much greater than for either of the milled wood lignin samples consistent with the presence of carboxyl groups and higher proportion of phenolic hydroxyl groups as shown by quantitative (31)P NMR on the phosphitylated samples. Furthermore, the total surface energy of lignin of 53-56 mJ m(-2) is of a similar magnitude to cellulose, also found in the wood cell wall; however, cellulose has a higher polar component leading to a lower contact angle with water and greater wettability than the milled wood lignin. Although lignin is not hydrophobic according to the strictest definition of a water contact angle greater than 90 degrees, water may only be considered a partially wetting liquid on a lignin surface. This supports the long-held belief that one of the functions of lignin in the wood cell wall is to provide water-proofing to aid in water transport. Furthermore, these results on the solid-vapor surface energy of lignin will provide invaluable insight for many natural and industrial applications including in the design and manufacture of many sustainable products such as paper, fiberboard, and polymer composite blends. PMID- 20349914 TI - DNA density-dependent assembly behavior of colloidal micelles. AB - A key advantage of DNA-mediated colloidal assembly is the ability to tune the strength of adhesion between particles based on sequence characteristics. In the current study, we have investigated DNA-mediated assembly of polystyrene colloidal particles as a function of sequence length, sequence fidelity, and probe density for DNA sequences patterned from the Salmonella genome. The results of our work indicate that the density of DNA probe strands heavily influences the ability of immobilized sequences to hybridize between surfaces of bidisperse colloidal particles. Incubating suspensions at higher temperatures (to minimize secondary structures that might otherwise compromise duplex formation) was also found to have less effect than duplex density on DNA-mediated particle assembly. We believe these results may add to the understanding and design considerations of directed particle assembly using DNA hybridization, especially in the submicrometer and micrometer size regime. PMID- 20349915 TI - Room temperature light emission from the low-dimensional semiconductors AZrPS6 (A = K, Rb, Cs). AB - The new semiconducting thiophosphate compounds KZrPS(6), RbZrPS(6), and CsZrPS(6) exhibit red light emission at room temperature. The materials have longer photoluminescence lifetimes than most of the inorganic chalcogenide semiconductors. They can be solution processed into thin films for potential device fabrication. PMID- 20349917 TI - NMR-spectroscopy for nontargeted screening and simultaneous quantification of health-relevant compounds in foods: the example of melamine. AB - The recent melamine crisis in China has pointed out a serious deficiency in current food control systems, namely, they specifically focus on selected known compounds. This targeted approach allowed the presence of melamine in milk products to be overlooked for a considerable time. To avoid such crises in the future, we propose that nontargeted screening methods need to be developed and applied. To this end, NMR has an extraordinary potential that just started to be recognized and exploited. Our research shows that, from the very same set of spectra, (1)H NMR at 400 MHz can distinguish between melamine-contaminated and melamine-free infant formulas and can provide quantitative information by integration of individual lines after identification. For contaminated Chinese infant formulas or candy, identical results were obtained when comparing NMR with SPE-LC/MS/MS. NMR was found to be suitable for routine nontargeted and targeted analyses of foods, and its use will significantly increase food safety. PMID- 20349916 TI - Targeted delivery of antigen processing inhibitors to antigen presenting cells via mannose receptors. AB - Improved chemical inhibitors are required to dissect the role of specific antigen processing enzymes and to complement genetic models. In this study we explore the in vitro and in vivo properties of a novel class of targeted inhibitor of aspartic proteinases, in which pepstatin is coupled to mannosylated albumin (MPC6), creating an inhibitor with improved solubility and the potential for selective cell tropism. Using these compounds, we have demonstrated that MPC6 is taken up via mannose receptor facilitated endocytosis, leading to a slow but continuous accumulation of inhibitor within large endocytic vesicles within dendritic cells and a parallel inhibition of intracellular aspartic proteinase activity. Inhibition of intracellular proteinase activity is associated with reduction in antigen processing activity, but this is epitope-specific, preferentially inhibiting processing of T cell epitopes buried within compact proteinase-resistant protein domains. Unexpectedly, we have also demonstrated, using quenched fluorescent substrates, that little or no cleavage of the disulfide linker takes place within dendritic cells. This does not appear to affect the activity of MPC6 as an inhibitor of cathepsins D and E in vitro and in vivo. Finally, we have shown that MPC6 selectively targets dendritic cells and macrophages in spleen in vivo. Preliminary results suggest that access to nonlymphoid tissues is very limited in the steady state but is strongly enhanced at local sites of inflammation. The strategy adopted for MPC6 synthesis may therefore represent a more general way to deliver chemical inhibitors to cells of the innate immune system, especially at sites of inflammation. PMID- 20349918 TI - Biscuit melanoidins of different molecular masses protect human HepG2 cells against oxidative stress. AB - Soluble melanoidins from biscuits were enzymatically solubilized and isolated by sequential ultrafiltration and separated by molecular mass in three different fractions, below 3 kDa, between 3 and 10 kDa, and over 10 kDa; the latter was subsequently digested by simulating gastric plus pancreatic digestive conditions. The four fractions were investigated for their protective effect against an oxidative challenge in HepG2 cells. Pretreatment of cells for 20 h with 0.5-10 microg/mL of any of the four fractions prevented the increased cell damage evoked by the challenge but, except for the intermediate size fraction, did not suppress the increased reactive oxygen species. Antioxidant defenses were rapidly restored after the challenge, and the increase of the oxidative stress biomarker malondialdehyde was prevented by the pretreatment with all but the undigested high molecular mass fraction. The results show that treatment of HepG2 cells with concentrations of biscuit melanoidins within the expected physiological range confers on the cells a significant protection against an oxidative challenge. PMID- 20349919 TI - Ontogenetic changes of 2-propenyl and 3-indolylmethyl glucosinolates in Brassica carinata leaves as affected by water supply. AB - Concentrations of 2-propenyl and 3-indolylmethyl glucosinolates in two lines of Brassica carinata (Holeta-1 and 37-A) were assessed during the vegetative life cycle under optimal or drought-inducing water supply conditions. In the well watered treatment, 2-propenyl and 3-indolylmethyl glucosinolate concentrations remained almost constant from the 6-8 to the 15-16 leaf stage, whereas a drought induced water supply led to a distinct increase of these glucosinolates. Generally, the 2-propenyl concentration was higher in Holeta-1 at each leaf stage under drought stress as compared with 37-A, indicating a B. carinata line specific drought response. The drought-induced glucosinolate accumulation seems to be integrated in the plant's process of osmotic adjustment. It seems that under drought, there is a shift from primary to secondary metabolism, thereby promoting glucosinolate synthesis. Thus, by keeping the relative soil-water content below 80%, glucosinolate concentrations could be increased up to the 15 16 leaf stage, resulting in better plant nutritional quality of B. carinata. PMID- 20349920 TI - Significance of the nonvolatile minor compounds of the neutral lipid fraction as markers of the origin of dairy products. AB - In the past few years several researchers have approached the problem of traceability of dairy products mainly by examining the volatile compounds that could be transferred from forage into milk and cheese. Our research focused on the study of the composition of the nonvolatile minor components of the neutral lipid fraction in mountain dairy products, obtained from animals feeding on pasture, and in milk and cheese samples produced from cows under intensive breeding, fed with concentrates and silages. Hydrocarbons were separated by silica gel column chromatography from the whole lipid matrix and analyzed by GC/MS. Among all the compounds detected, 1-phytene, 2-phytene, neophytadiene, and to a lesser extent the esters of phytol with C16 and C18 fatty acids seem to be promising tools for the recognition of the feeding system. The value of the sum of isoprenoid hydrocarbons (summation operator-hyd) of mountain dairy products (12.3-34.0 mg/kg) was always higher than that obtained from plain samples (1.3 6.4 mg/kg). PMID- 20349921 TI - Absence of pomegranate ellagitannins in the majority of commercial Pomegranate extracts: implications for standardization and quality control. AB - The health benefits associated with pomegranate juice have led to the development of pomegranate extracts as botanical dietary supplements. Pomegranates contain hydrolyzable tannins in the form of punicalagins and punicalin as well as tannin based complex oligomers that account for much of the antioxidant activity in juice. The content of ellagic acid has been used to standardize most pomegranate extract dietary supplements marketed. However, supplements can be adulterated with ellagic acid from less expensive plant sources and undercut this method of standardization. To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity. Future research is needed to assess the health impact of substituting ellagic acid for the complex mix of phytochemicals in a pomegranate extract dietary supplement. PMID- 20349922 TI - Slow digestion properties of rice different in resistant starch. AB - The hydrolysis of starch is a key factor for controlling the glycemic index (GI). Slow digestion properties of starch lead to slower glucose release and lower glycemic response. Food with high resistant starch (RS) possesses great value for controlling the GI. To elucidate the factors that play a role in slow digestibility, seven rice mutants different in RS contents were selected for comparative studies. The degree of hydrolysis showed highly significant correlation with RS, apparent amylose content (AAC), lipid content (LC), and other starch physiochemical properties in all these materials with different RS contents. The rate of in vitro digestible starch correlated positively with RS, whereas digestibility was affected mostly by lipid content for those mutants with similar RS. Starch-lipid complexes and short chains with degrees of polymerization (DP) of 8-12 strongly influenced starch digestion. The integrity of aggregated starch and the number of round starch granules might influence the digestibility of starch directly. PMID- 20349923 TI - Sorption and interaction of the flavonoid naringenin on tomato fruit cuticles. AB - The flavonoid naringenin accumulates in tomato fruit epidermis during ripening. The sorption of this flavonoid to enzymatically isolated cuticles of Solanum lycopersicum was studied as a function of the temperature and naringenin concentration at two stages of fruit growth. The selected stages were mature green, without flavonoids in the cuticle, and ripe tomato, with significant amounts of flavonoids in the cuticle. Sorption isotherms showed different behaviors that could be explained in terms of different affinities of the sorbed flavonoid for the cuticular matrix. The partition coefficient of naringenin in the system cuticle/water solution was a function of temperature and concentration. Changes in the free energy, enthalpy, and entropy for the phase transfer of naringenin to cuticle were also calculated, indicating the existence of naringenin-naringenin interactions replacing naringenin-cuticular matrix interactions at high concentrations with the final result of solid precipitations in the form of clusters within the cutin matrix. PMID- 20349924 TI - Characterization of conjugated linoleic acid production by Bifidobacterium breve LMC 520. AB - This study was performed to characterize the CLA production ability of a bacterial strain, Bifidobacterium breve LMC 520, which can actively convert linoleic acid (LA) to cis-9,trans-11 conjugated linoleic acid (CLA), a major isomer derived from microbial enzymatic conversion. The culture conditions were optimized to improve CLA production under the aerobic conditions. B. breve LMC 520 was tested with different amounts of LA in varied culture conditions, such as air, additives, and pH. A maximal level of CLA production (up to 90% of substrate) was obtained after 24 h of incubation in culture medium containing 1 mM LA at pH 5.5 and under anaerobic conditions. There was no decline in the CLA level with prolonged incubation until 48 h. When the effect of pre-incubation with LA on CLA production was tested, there was no significant difference between the CLA-producing activity of pre-incubated and untreated bacteria at the third passage but there was a significant reduction in CLA production by the pre incubated cells after the fourth passage. These results demonstrate that the CLA producing activity of B. breve LMC 520 could be maximized by numerous environmental factors. The data also indicate its potential for increasing CLA accumulation in dairy products when B. breve LMC 520 is used as a functional starter culture. PMID- 20349925 TI - Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. AB - Several studies have shown that gallic acid (GA) induces apoptosis in different cancer cell lines, whereas the mechanism of action of GA-induced apoptosis at the molecular level in human non-small-cell lung cancer NCI-H460 cells is not well known. Here, GA decreasing the percentage of viable NCI-H460 cells was investigated; GA-induced apoptosis involved G2/M phase arrest and intracellular Ca(2+) production, the loss of mitochondrial membrane potential (DeltaPsi(m)), and caspase-3 activation. The efficacious induction of apoptosis and DNA damage was observed at 50-500 microM for 24 and/or 48 h as examined by flow cytometry, DAPI staining, and Comet assay methods. Western blotting and flow cytometric analysis also demonstrated that GA increased protein levels of GADD153 and GRP78, activation of caspase-8, -9, and -3, loss of DeltaPsi(m) and cytochrome c, and AIF release from mitochondria. Moreover, apoptosome formation and activation of caspase cascade were associated with apoptotic cell death. GA increased Bax and Bad protein levels and decreased Bcl-2 and Bcl-xL levels. GA may also induce apoptosis through a caspase-independent AIF pathway. In nude mice bearing NCI H460 xenograft tumors, GA inhibited tumor growth in vivo. The data suggest that GA induced apoptosis in NCI-H460 lung cancer cells via a caspase-3 and mitochondrion-dependent pathway and inhibited the in vivo tumor growth of NCI H460 cells in xenograft models. PMID- 20349926 TI - Surface investigation on biomimetic materials to control cell adhesion: the case of RGD conjugation on PCL. AB - The cell recognition of bioactive ligands immobilized on polymeric surfaces is strongly dependent on ligand presentation at the cell/material interface. While small peptide sequences such as Arg-Gly-Asp (RGD) are being widely used to obtain biomimetic interfaces, surface characteristics after immobilization as well as presentation of such ligands to cell receptors deserve more detailed investigation. Here, we immobilized an RGD-based sequence on poly(epsilon caprolactone) (PCL), a largely widespread polymeric material used in biomedical applications, after polymer aminolysis. The surface characteristics along with the efficacy of the functionalization was monitored by surface analysis (FTIR ATR, contact angle measurements, surface free energy determination) and spectrophotometric assays specially adapted for the analytical quantification of functional groups and/or peptides at the interface. Particular attention was paid to the evaluation of a number, morphology, and penetration depth of immobilized functional groups and/or peptides engrafted on polymeric substrates. In particular, a typical morphology in peptide distribution was evidenced on the surface raised from polymer crystallites, while a significant penetration depth of the engrafted molecules was revealed. NIH3T3 fibroblast adhesion studies verified the correct presentation of the ligand with enhanced cell attachment after peptide conjugation. Such work proposes a morphological and analytical approach in surface characterization to study the surface treatment and the distribution of ligands immobilized on polymeric substrates. PMID- 20349927 TI - Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events. AB - We report the photoinduced peptide bond (C-N) of an amide unit and S-S bond fission mechanisms of the cyclic tetrapeptide [cyclo(Boc-Cys-Pro-Aib-Cys-OMe)] in methanol solvent by using high-level CASSCF/CASPT2/Amber quantum mechanical/molecular mechanical (QM/MM) calculations. The subsequent energy transport and unfolding-refolding events are characterized by using a semiempirical QM/MM molecular dynamics (MD) simulation methodology that is developed in the present work. In the case of high-energy excitation with <193 nm light, the tetrapeptide molecule in the (1)n pi* surface overcomes two barriers with approximately 10.0 kcal/mol, respectively, and uses energy consumption for breaking the hydrogen bond as well as the N-C bond in the amide unit, ultimately leading to the ground state via a conical intersection of CI (S(NP)/S(0)) by structural changes of an increased N-C distance and a O-C-C angle in the amide unit (a two-dimensional model of the reaction coordinates). Following this point, relaxation to a hot molecule with its original structure in the ground state is the predominant decay channel. A large amount of heat (approximately 110.0 kcal/mol) is initially accumulated in the region of the targeted point of the photoexcitation, and more than 60% of the heat is rapidly dissipated into the solvent on the femtosecond time scale. The relatively slower propagation of heat along the peptide backbone reaches a phase of equilibration within 3 ps. A 300 nm photon of light initiates the relaxation along the repulsive S(sigma sigma)((1)sigma sigma*) state and this decays to the CI (S(sigma sigma)/S(0)) in concomitance with the separation of the disulfide bond. Once cysteinyl radicals are generated, the polar solvent of methanol molecules rapidly diffuses around the radicals, forming a solvent cage and reducing the possibility of close contact in a physical sense. The fast unfolding-refolding event is triggered by S S bond fission and powered by dramatic thermal motion of the methanol solvent that benefits from heat dissipation. The beta-turn opening (unfolding) can be achieved in about 120 ps without the inclusion of the time associated with the photochemical steps and eventually relaxes to a 3(10)-helix structural architecture (refolding) within 200 ps. PMID- 20349928 TI - Solubilizing carbon nanotubes through noncovalent functionalization. Insight from the reversible wrapping of alginic acid around a single-walled carbon nanotube. AB - Carbon nanotubes coated with alginic acid (AA) through noncovalent functionalization have been shown to be soluble and dispersed in water. In the present contribution, all-atom molecular dynamics simulations have been performed to probe the self-assembly mechanism that underlies the formation of complexes by AA and a single-walled carbon nanotube (SWCNT), both in the gas phase and in an aqueous solution. Results of these simulations reveal that AA can wrap around SWCNT by virtue of van der Waals attractions and organize into a compact helical structure, a process induced in the gas phase by hydrogen-bonding interactions. In contrast, in an alginate aqueous solution, a loose helical wrapping mode is found to be favored by virtue of electrostatic repulsions in conjunction with the weakening of hydrogen-bonding interactions. Documented experimentally (Liu, Y.; et al. Small 2006, 2, 874-878) and coined "Great Wall of China" motif, the typical arrangement of AA residues around the tubular structure, conducive to dissolve nanotubes, is observed in the present simulations. Investigation of metal cations binding to AA suggests that calcium ions can mediate aggregation of AA chains by interacting strongly with the carboxylate groups, thereby leading to reverse unwrapping. The results reported in this work shed meaningful light on the potential of noncovalent functionalization for solubilizing carbon nanotubes, and open exciting perspectives for the design of new wrapping agents that are envisioned to form the basis of innovative nanomaterials targeted at chemical and biomedical applications. PMID- 20349930 TI - Molecular dynamics study on glass transitions in atactic-polypropylene bulk and freestanding thin films. AB - Molecular dynamics simulation has been adopted in investigation of different glass transition behaviors of the bulk and the freestanding thin films (about 8 nm) of atactic polypropylene (a-PP). For characterization of glass transition temperature (T(g)) of above systems, both the specific volume and the local conformational transition rate of the systems were examined. The T(g) characterization from the local conformational transition rate of polymer chains was recently developed. Our simulation results show that the films have lower T(g) than the bulk, and the descent of T(g) is in a range of 30 approximately 10 K. These are consistent with experiments. a-PP chain consists of meso-dyad and racemic-dyad, the above results are obtained from both dyads. Individual contribution of the stereoregular dyads to the conformational transition rate was further studied. It was revealed that T(g) obtained singly from the meso-dyads was almost the same with T(g) individually from the racemic-dyads, although the racemic-dyads have much lower transition rate and higher transition barrier than the meso-dyads. In the present study, the reason for the thin films having lower T(g) than the bulk is attributed to the novel behavior that the films have lower transition rate and higher barrier than the bulk when it is below T(g). Such behavior was discussed according to the "coupling rotation" of the dihedrals, which depends on the increase of free volume and the inhibition of kinetic energy. PMID- 20349929 TI - A substrate selectivity and inhibitor design lesson from the PDE10-cAMP crystal structure: a computational study. AB - Phosphodiesterases (PDEs) catalyze the hydrolysis of second messengers cAMP and cGMP in regulating many important cellular signals and have been recognized as important drug targets. Experimentally, a range of specificity/selectivity toward cAMP and cGMP is well-known for the individual PDE families. The study reported here reveals that PDEs might also exhibit selectivity toward conformations of the endogenous substrates cAMP and cGMP. Molecular dynamics simulations and free energy study have been applied to study the binding of the cAMP torsional conformers about the glycosyl bond in PDE10A2. The computational results elucidated that PDE10A2 is energetically more favorable in complex with the syn cAMP conformer (as reported in the crystal structure) and the binding of anti cAMP to PDE10A2 would lead to either a nonreactive configuration or significant perturbation on the catalytic pocket of the enzyme. This experimentally inaccessible information provides important molecular insights for the development of effective PDE10 ligands. PMID- 20349931 TI - Neuromedin C: potential-dependent surface-enhanced Raman spectra in the far-red spectral region on silver, gold, and copper surfaces. AB - Neuromedin C (NMC) is a decapeptide (Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met NH(2)) that acts as a growth factor in a wide range of tumors including carcinomas of the pancreas, stomach, breast, prostate, and colon. We report surface-enhanced Raman spectra (SERS) of NMC on electrochemically roughened Ag, Au, and Cu electrode surfaces over an electrode potential range varying from +0.200 to -1.200 V (depending on the electrode material). We compared the SERS spectra to the Raman spectrum of the corresponding solid species. The SERS spectra were dominated by L-tryptophan (Trp) vibrations. This indicates that Trp interacted with the metallic surfaces of the electrodes, either by binding directly to the surface or by staying in close proximity to the surface. Characteristic SERS bands showed that, in the case of the Ag electrode, the Trp residue was almost perpendicular to the surface. In contrast, the Trp residue was slightly tilted with respect to the Au electrode surface, and Trp remained some distance from the surface of the Cu electrode. These differences were due to differences in surface rheology and in the type of metal (Ag vs Au vs Cu) responsible for the observed enhancement mechanism. On the other hand, variations in the electrode potentials only had a slight influence on the SERS patterns and the observed changes were mainly due to the reorientation of the Trp ring with respect to the electrode surface. These findings were fully supported by generalized two-dimensional correlation analysis (G2DCA). PMID- 20349932 TI - Aggregation behavior of triple helical polysaccharide with low molecular weight in diluted aqueous solution. AB - It has been proven in our previous work that the lentinan triple helical chains with high weight-average molecular weight (M(w) = 1.71 x 10(6)) formed easily a self-entangle one, and no ordered aggregates were detected. In the present work, we used the ultrasonic method to degrade the lentinan triple helical chains to obtain a sample with a mean value of M(w) approximately 5.0 x 10(5) g/mol. Subsequently, its dilute aqueous solution properties were studied by dynamic light scattering (DLS). The relaxation time distributions exhibited two modes (fast and slow) with different relaxation time scales. The fast mode was attributed to the relaxation of an individual triple helical lentinan, whereas the slow mode indicated the formation of large aggregates. On the basis of the scattering wave vector dependencies for the scattering intensity and for the amplitudes and characteristic times associated with the relaxation modes, the molecular parameters were calculated by combing static LS with DLS. The values of the radius of gyration for individuals (R(g)(indi)) and aggregates (R(g)(agg)) were 48.2 and 75.4 nm, and those of the hydrodynamic radius for individuals (R(h)(indi)) and aggregates (R(h)(agg)) were 14.9 and 98.4 nm, respectively. Furthermore, the structure-sensitive dimensionless parameter of individuals (rho(indi) = 3.23) and aggregates (rho(agg) = 0.766) indicated that the individual triple helical chains were stiff, whereas the aggregates existed as compact clusters. The aggregates consisted of short triple helical chains by packing close to form "faggot-like" assembly, and the ordered aggregates (near 10%) coexisted with the predominant triple helical chain in the aqueous solution. Atomic force microscopy provided straightforward evidence on the shape of the triple helical chains and their aggregates in water. PMID- 20349933 TI - The effect of AC frequency on the electrowetting behavior of ionic liquids. AB - This paper presents a study of electrowetting of ionic liquids (ILs) under AC voltages, where nine different ILs (including mono-, di-, and tricationic varieties) with three different AC frequencies (60 Hz, 1 kHz, 10 kHz) were experimentally investigated. The main foci of this study are (i) an investigation of AC frequency dependence on the electrowetting of ILs; (ii) obtaining theoretical relationships between the relevant factors that explain the experimentally achieved frequency dependence; and (iii) a systematic comparison of electrowetting of ILs using AC vs DC voltage fields. The frequency of the AC voltage was found to be directly related to the apparent contact angle change (Deltatheta) of the ILs. This relationship was further analyzed and explained theoretically. The electrowetting properties of ILs under AC voltages were compared to that under DC voltages. All tested ILs showed greater apparent contact angle changes with AC voltage conditions than with DC voltage conditions. The effect of structure and charge density also was examined. Electrowetting reversibility under AC voltage conditions was studied for few ILs. Finally, the physical properties and AC electrowetting properties of ILs were measured and tabulated. PMID- 20349935 TI - Revealing different bonding modes of self-assembled octadecylphosphonic acid monolayers on oxides by time-of-flight secondary ion mass spectrometry: silicon vs aluminum. AB - Condensed octadecylphosphonic acid (OPA) dimers, i.e., two OPA molecules combined with the loss of a water molecule, were detected by time-of-flight secondary ion mass spectrometry (TOF-SIMS) on OPA self-assembled monolayers (SAMs) that are only weakly bonded on the native oxide layer of a silicon wafer. In contrast, these condensed dimers were absent on OPA SAMs formed on the oxide layer of an aluminum film, where the OPA molecules are chemically bonded on the substrate through a P-O-Al linkage. These observations lead us to conclude that the OPA molecules in their SAMs have to be free from chemical bonding with the substrate in order for the primary ion beam to generate ion fragments of the condensed dimer. We demonstrate that the detection of condensed OPA dimers serves as an analytical criterion for TOF-SIMS to reveal the bonding mode of OPA molecules in their SAMs on different oxides. PMID- 20349936 TI - An experimental solution to the "missing hydrogens" question surrounding the macropolyhedral 19-vertex boron hydride monoanion [B19H22]-, a simplification of its synthesis, and its use as an intermediate in the first example of syn-B18H22 to anti-B18H22 isomer conversion. AB - The macropolyhedral [B(19)H(22)](-) monoanion 1 and the dianion [B(19)H(21)](2-) 2 are synthesized in consistent 86-92% yields by the reaction of [PSH](+)[syn B(18)H(21)](-) with BH(3)(SMe(2)) in 1,2-Cl(2)C(2)H(4) at 72 degrees C. ['PS' is an abbreviation for 'Proton Sponge', 1,8-bis-(dimethylamino)naphthalene. 'PSH' is its protonated derivative.] The molecular structures of 1 and 2 were elucidated as their [PS{BH(2)}](+) and [PS{BH(2)}](2)(+) salts 1a and 2a by single-crystal X ray diffraction studies, in which all atoms were located, and supported by mass spectrometric analyses together with calculations of the cluster molecular geometries (ab ignitio and/or DFT) and of (11)B chemical shifts based on GIAO-DFT shielding tensors. Acidification of dianion 2 with CF(3)COOH in acetonitrile, H(2)SO(4) in dichloromethane, or aqueous HCl results in the clean formation of the monoanion [B(19)H(22)](-) 1. Conversely, shaking a concentrated acetonitrile solution of 1 in 0.5 M aqueous NaOH cleanly yields the [B(19)H(21)](2-) dianion 2. Reaction of a dichloromethane solution of 1 with a 36% aqueous solution of HCHO in the presence of H(2)SO(4) quantitatively converts 1 at room temperature to a 1:1 mixture of the syn- and anti-isomers of B(18)H(22). This cluster dismantling process is the first example of a syn- to anti-B(18)H(22) isomer conversion. PMID- 20349937 TI - Structural analysis of pentacene thin film growth on polycrystalline Ox-Au surfaces using scanning tunneling microscopy. AB - In this letter, we show the feasibility to use scanning tunneling microscopy (STM) as a stand-alone technique in analyzing the structure of organic thin films grown on polycrystalline metal surfaces. At room temperature, by effectively suppressing the molecule-substrate interaction, pentacene resumes the typical quasi layer-by-layer growth with the "thin-film phase" structure due to intermolecule interaction, while substrate roughness does not play an important role. By elevating the substrate to 320 K, two different polycrystalline phases, that is, the "thin-film phase" and the "single-crystal phase" intermixed grow and form terraced and lamellar structures, respectively. Using STM distance-voltage spectroscopy, the energy level alignment of the underlying organic/metal interfaces can also be acquired. PMID- 20349938 TI - Assembling nonspherical 2D binary nanoparticle superlattices by opposite electrical charges: the role of Coulomb forces. AB - High-quality approximately 16 nm c-In2O3 nanoctahedra and approximately 6 nm Pd spherical nanoparticles were synthesized via a high-temperature wet-chemical approach, and their electrophoretic mobilities in toluene were investigated, respectively. Opposite electrical charge-induced 2D binary nanoparticle superlattice patterns containing two such nanocomponents were prepared, for the first time. Three types of c-In2O3-skeleton-structure-contained assembly patterns were identified as well. It was further observed that the vertices of c-In2O3 nanoctahedra could have higher electrical charge density than that on edge or plane and the small Pd nanoparticles were "suspended" on the middle plane of the c-In2O3 nanoctahedra, apparently well above the substrate surface (support film) rather than sitting on it. The assembly structure study indicates that Coulomb forces resulted from the opposite electrical charges are the dominative driving forces to induce the formation of such nanoctahedra-nanospheres 2D binary nanoparticle superlattices. PMID- 20349939 TI - Sensitization of nanocrystalline TiO2 anchored with pendant catechol functionality using a new tetracyanato ruthenium(II) polypyridyl complex. AB - We have synthesized a new photoactive ruthenium(II) complex having a pendant catechol functionality (K(2)[Ru(CN)(4)(L)] (1) (L is 4-[2-(4'-methyl-2,2' bipyridinyl-4-yl)vinyl]benzene-1,2-diol) for studying the dynamics of the interfacial electron transfer between nanoparticulate TiO(2) and the photoexcited states of this Ru(II) complex using femtosecond transient absorption spectroscopy. Steady-state absorption and emission studies revealed that the complex 1 showed a strong solvatochromic behavior in solvents or solvent mixtures of varying polarity. Our steady-state absorption studies further revealed that 1 is bound to TiO(2) surfaces through the catechol functionality, though 1 has two different types of functionalities (catecholate and cyanato) for binding to TiO(2) surfaces. The longer wavelength absorption band tail for 1, bound to TiO(2) through the proposed catecholate functionality, could also be explained on the basis of the DFT calculations. Dynamics of the interfacial electron transfer between 1 and TiO(2) nanoparticles was investigated by studying kinetics at various wavelengths in the visible and near-infrared region. Electron injection to the conduction band of the nanoparticulate TiO(2) was confirmed by detection of the conduction band electron in TiO(2) ([e(-)](TiO(2))(CB)) and cation radical of the adsorbed dye (1(*+)) in real time as monitored by transient absorption spectroscopy. A single exponential and pulse-width limited (<100 fs) electron injection was observed. Back electron transfer dynamics was determined by monitoring the decay kinetics of 1(*+) and [e(-)](TiO(2))(CB). This is the first report on ultrafast ET dynamics on TiO(2) nanoparticle surface using a solvatochromic sensitizer molecule. PMID- 20349940 TI - Stylissamides E and F, cyclic heptapeptides from the caribbean sponge Stylissa caribica. AB - In addition to the four known stylissamides, A (1), B (2), C, and D, two new cyclic heptapeptides, stylissamides E (3) and F (4), were isolated from the Caribbean sponge Stylissa caribica. The structures of 3 and 4 were elucidated from a combination of mass spectrometric and NMR spectroscopic data as cyclo-(cis Pro(1)-Tyr(2)-trans-Pro(3)-Ala(4)-Ile(5)-Gln(6)-Ile(7)) for stylissamide E (3) and cyclo-(trans-Pro(1)-cis-Pro(2)-Phe(3)-Asp(4)-trans-Pro(5)-Arg(6)-Phe(7)) for stylissamide F (4). PMID- 20349941 TI - Three synthetic routes to single-crystalline PbS nanowires with controlled growth direction and their electrical transport properties. AB - Single-crystalline rock-salt PbS nanowires (NWs) were synthesized using three different routes; the solvothermal, chemical vapor transport, and gas-phase substitution reaction of pregrown CdS NWs. They were uniformly grown with the [100] or [110], [112] direction in a controlled manner. In the solvothermal growth, the oriented attachment of the octylamine (OA) ligands enables the NWs to be produced with a controlled morphology and growth direction. As the concentration of OA increases, the growth direction evolves from the [100] to the higher surface-energy [110] and [112] directions under the more thermodynamically controlled growth conditions. In the synthesis involving chemical vapor transport and the substitution reaction, the use of a lower growth temperature causes the higher surface-energy growth direction to change from [100] to [110]. The high resolution X-ray diffraction pattern and X-ray photoelectron spectroscopy results revealed that a thinner oxide-layer was produced on the surface of the PbS NWs by the substitution reaction. We fabricated field effect transistors using single PbS NW, which showed intrinsic p-type semiconductor characteristics for all three routes. For the PbS NW with a thinner oxide layer, the carrier mobility was measured to be as high as 10 cm(2) V(-1) s(-1). PMID- 20349942 TI - High on-off conductance switching ratio in optically-driven self-assembled conjugated molecular systems. AB - A new azobenzene-thiophene molecular switch is designed, synthesized, and used to form self-assembled monolayers (SAM) on gold. An "on/off" conductance ratio up to 7 x 10(3) (with an average value of 1.5 x 10(3)) is reported. The "on" conductance state is clearly identified to the cis isomer of the azobenzene moiety. The high on/off ratio is explained in terms of photoinduced, configuration-related changes in the electrode-molecule interface energetics (changes in the energy position of the molecular orbitals with respect to the Fermi energy of electrodes) in addition to changes in the tunnel barrier length (length of the molecules). First principles density functional calculations demonstrate a better delocalization of the frontier orbitals as well as a stronger electronic coupling between the azobenzene moiety and the electrode for the cis configuration over the trans one. Measured photoionization cross sections for the molecules in the SAM are close to the known values for azobenzene derivatives in solution. PMID- 20349943 TI - A glass forming module for organic molecules: making tetraphenylporphyrin lose its crystallinity. AB - Formation of stable glassy phases can be induced through rational design in compounds which otherwise readily crystallize, such as tetraphenylporphyrin, by simple functionalization with moieties known to promote glass formation such as mexylaminotriazine units. PMID- 20349944 TI - Tandem oxidation/rearrangement of beta-ketoesters to tartronic esters with molecular oxygen catalyzed by calcium iodide under visible light irradiation with fluorescent lamp. AB - It was found that beta-ketoesters were directly transformed to the corresponding alpha-hydroxymalonic esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide under visible light irradiation from fluorescent lamp. This reaction includes tandem oxidation/rearrangement and has received much attention from the viewpoint of reduction of energy consumption, labor, and solvents. PMID- 20349945 TI - Highly chemo- and enantioselective synthesis of 3-allyl-3-aryl oxindoles via the direct palladium-catalyzed alpha-arylation of amides. AB - A new NHC x Pd-catalyzed asymmetric alpha-arylation of amides is reported that gives direct access to synthetically valuable, allylated oxindoles with quaternary carbon centers. The reaction is made possible by the introduction of a new chiral NHC ligand. The palladium complexes derived therefrom combine excellent reactivity with high chemo- and enantioselectivity for the title transformation. PMID- 20349946 TI - Synthesis of 2,3-dihydroselenophene and selenophene derivatives by electrophilic cyclization of homopropargyl selenides. AB - The synthesis of several highly functionalized 2,3-dihydroselenophenes from homopropargyl selenides via electrophilic cyclization is described. Electrophiles such as I(2), ICl, and PhSeBr were used in a simple process employing CH(2)Cl(2) as solvent at room temperature, which gave the cyclized products in high yields. 4-Iodo-2,3-dihydroselenophenes obtained by this methodology were submitted to a dehydrogenation reaction using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to give 3-iodoselenophenes. 4-Iodo-5-phenyl-2,3-dihydroselenophene was also submitted to the thiol copper-catalyzed and Heck-type reactions giving the desired products under mild reaction conditions. PMID- 20349947 TI - Enantioselective synthesis of planar-chiral 1,n-dioxa[n]paracyclophanes via catalytic asymmetric ortho-lithiation. AB - Highly enantioselective ortho-lithiation and dilithiation of 1,n dioxa[n]paracyclophanes were realized with the use of sec-butyllithium and a catalytic or stoichiometric amount of sparteine. Quenching with various electrophiles, such as iodine, iodomethane, and chlorodiphenylphosphine, afforded chiral mono- and disubstituted paracyclophanes with good to excellent ee. PMID- 20349949 TI - Intracellular delivery of the reactive oxygen species generating agent D penicillamine upon conjugation to poly-L-glutamic acid. AB - D-penicillamine is an aminothiol that is cytotoxic to cancer cells and generates dose dependent reactive oxygen species (ROS) via copper catalyzed oxidation. However, the delivery of D-pen to cancer cells remains a challenge due to its high hydrophilicity, highly reactive thiol group and impermeability to the cell membrane. To overcome this challenge, we investigated a novel poly-L-glutamic acid (PGA) conjugate of D-pen (PGA-D-pen) where D-pen was conjugated to PGA modified with 2-(2-pyridyldithio)-ethylamine (PDE) via disulfide bonds. Confocal microscopy and cell uptake studies showed that the fluorescently labeled PGA-D pen was taken up by human leukemia cells (HL-60) in a time dependent manner. Treatment of HL-60, murine leukemia cells (P388) and human breast cancer cells (MDA-MB-468) with PGA-D-pen resulted in dose dependent cytotoxicity and elevation of intracellular ROS levels. PGA-D-pen induced apoptosis in HL-60 cells which was verified by Annexin V binding. The in vivo evaluation of the conjugate in the P388 murine leukemia model (intraperitoneal) resulted in significant enhancement in the survival of CD2F1 mice over vehicle control. PMID- 20349948 TI - Development of a novel self-microemulsifying drug delivery system for reducing HIV protease inhibitor-induced intestinal epithelial barrier dysfunction. AB - The development of HIV protease inhibitors (PIs) has been one of the most significant advances of the past decade in controlling HIV infection. Unfortunately, the benefits of HIV PIs are compromised by serious side effects. One of the most frequent and deleterious side effects of HIV PIs is severe gastrointestinal (GI) disorders including mucosal erosions, epithelial barrier dysfunction, and leak-flux diarrhea, which occurs in 16-62% of patients on HIV PIs. Although the underlying mechanisms behind HIV PI-associated serious adverse side effects remain to be identified, our recent studies have shown that activation of endoplasmic reticulum (ER) stress response plays a critical role in HIV PI-induced GI complications. The objective of this study was to develop a novel self-microemulsifying drug delivery system (SMEDDS) using various antioxidants as surfactants and cosurfactants to reduce the GI side effects of the most commonly used HIV PI, ritonavir. The biological activities of this SMSDDS of ritonavir were compared with that of Norvir, which is currently used in the clinic. Rat normal intestinal epithelial cells (IEC-6) and mouse Raw 264.7 macrophages were used to examine the effect of new SMEDDS of ritonavir on activation of ER stress and oxidative stress. Sprague-Dawley rats and C57/BL6 mice were used for pharmacokinetic studies and in vivo studies. The intracellular and plasma drug concentrations were determined by HPLC analysis. Activation of ER stress was detected by Western blot analysis and secreted alkaline phosphatase (SEAP) reporter assay. Reactive oxygen species (ROS) was measured using dichlorodihydrofluorescein diacetate as a probe. Cell viability was determined by Roche's cell proliferation reagent WST-1. Protein levels of inflammatory cytokines (TNF-alpha and IL-6) were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal permeability was assessed by luminal enteral administration of fluorescein isothiocyanate conjugated dextran (FITC-dextran, 4 kDa). The pathologic changes in intestine were determined by histological examination. The results indicated that incorporation of antioxidants in this new SMEDDS not only significantly reduced ritonavir-induced ER stress activation, ROS production and apoptosis in intestinal epithelial cells and macrophages, but also improved the solubility, stability and bioavailability of ritonavir, and significantly reduced ritonavir-induced disruption of intestinal barrier function in vivo. In conclusion, this new SMEDDS of ritonavir has less GI side effects compared to Norvir. This new SMEDDS can be used for other HIV PIs and any insoluble antiviral drug with serious GI side effects. PMID- 20349950 TI - Anticoagulant efficacy of solid oral formulations containing a new heparin derivative. AB - The need for an efficacious and safe oral anticoagulant that does not require monitoring has been largely unmet. Many efforts have centered on preparing orally available heparin to improve patient compliance. In this study, novel orally active heparin derivatives (LHD), i.e. low molecular weight heparin (LMWH) conjugated with deoxycholic acid (DOCA), were evaluated in vitro and in vivo for their enhancement effect of oral heparin absorption. After oral administration of 10 mg/kg of water-soluble LHD, Ws-LHD1.5 showed optimum oral efficacy and its bioavailability was about 24% in rats. The oral absorption of LHD1.5 was also enhanced by several solubilizers, among which Poloxamer 407 provided the best results. When 5 mg/kg of LHD1.5 with Poloxamer 407 was orally administered to monkeys, the maximum anti-FXa activity in plasma was 0.26 +/- 0.04 IU/mL and its bioavailability was 17.4%. In a rat thrombosis model, 5 mg/kg of orally administered LHD1.5 formulated with Poloxamer reduced thrombus formation by 63.9 +/- 16.6%, which was higher than the efficacy of clinically used enoxaparin (49.4 +/- 17.8% at 100 IU/kg, sc). Considering the oral absorption efficacy and therapeutic effect, the conjugation ratio was optimized as about 1.5 molecules of DOCA per mole of heparin. Therefore, LHD1.5 with Poloxamer 407 can be further formulated as a solid oral anticoagulant drug. PMID- 20349952 TI - Topical delivery of interferon alpha by biphasic vesicles: evidence for a novel nanopathway across the stratum corneum. AB - Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN alpha), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN alpha intercellularly, to a depth of 70 microm, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN alpha by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN alpha below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN alpha. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible. PMID- 20349953 TI - Solution phase parallel synthesis of substituted 3-phenylsulfonyl [1,2,3]triazolo[1,5-a]quinazolines: selective serotonin 5-HT(6) receptor antagonists. AB - Here we present the solution phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5 a]quinazolines and a study of the relation of their structure with a 5-HT(6) receptor antagonistic activity in a functional cell (HEK 293) analysis and radioligand competitive binding. We have found highly active and selective 5 HT(6)R antagonists. The most active 5-HT(6)R antagonists have IC(50) <100 nM in a functional assay, and K(i) <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors. PMID- 20349955 TI - A microscopic-macroscopic analysis for mixed energy transfer schemes in doped amorphous solids. AB - In this study we propose a methodology to treat mixed and more complex energy transfer schemes to reach the time-dependent intensities of luminescence in doped amorphous materials. We start outlining the differential equations for the time variation of microscopic probabilities of being in the relevant states and then transforming them into equations for the variation of the relevant macroscopic states populations and solve those equations. By this method, statistical approaches to the initially excited and up-converted states transient populations for up-conversion processes in the presence of cross relaxation in lanthanide monodoped amorphous solid are calculated. The resultant formulations produce plots that show correct general tendencies and are coherent with what would be expected for systems exhibiting both mechanisms, hence they could be used in the fitting of experimental curves to calculate some important parameters. The new solution method is more convenient that the classical analysis because it permits the introduction of more realistic time dependent functions for the interacting optical centers and allows showing the time dependence of the macroscopic energy transfer rates in the equations for the dynamics of the involved populations. We apply our method to the particular case of mixing of up-conversion and cross relaxation phenomena; however, because of its general characteristics, we suggest it could be applied to other mixings or more complex schemes. PMID- 20349954 TI - Detecting cross-linked peptides by searching against a database of cross-linked peptide pairs. AB - Mass spectrometric identification of cross-linked peptides can provide valuable information about the structure of protein complexes. We describe a straightforward database search scheme that identifies and assigns statistical confidence estimates to spectra from cross-linked peptides. The method is well suited to targeted analysis of a single protein complex, without requiring an isotope labeling strategy. Our approach uses a SEQUEST-style search procedure in which the database is comprised of a mixture of single peptides with and without linkers attached and cross-linked products. In contrast to several previous approaches, we generate theoretical spectra that account for all of the expected peaks from a cross-linked product, and we employ an empirical curve-fitting procedure to estimate statistical confidence measures. We show that our fully automated procedure successfully reidentifies spectra from a previous study, and we provide evidence that our statistical confidence estimates are accurate. PMID- 20349956 TI - Solid-state 115In and 31P NMR studies of triarylphosphine indium trihalide adducts. AB - Solid-state (115)In and (31)P NMR spectroscopy, relativistic density functional theory (DFT) calculations, and single-crystal X-ray diffraction were used to investigate a series of triarylphosphine indium(III) trihalide adducts, X(3)In(PR(3)) and X(3)In(PR(3))(2) (X = Cl, Br or I; PR(3) = triarylphosphine ligand). The electric field gradient tensors at indium as well as the indium and phosphorus magnetic shielding tensors and the direct and indirect (115)In-(31)P spin-spin coupling were characterized; for complexes possessing a C(3) symmetry axis, the anisotropy in the indirect spin-spin coupling, DeltaJ((115)In,(31)P), was also determined. The (115)In quadrupolar coupling constants, C(Q)((115)In), range from +/-1.25 +/- 0.10 to -166.0 +/- 2.0 MHz. For any given phosphine ligand, the indium nuclei are most shielded for X = I and least shielded for X = Cl, a trend also observed for other group-13 nuclei in M(III) complexes. This experimental trend, attributed to spin-orbit effects of the halogen ligands, is reproduced by the DFT calculations. The spans of the indium magnetic shielding tensors for these complexes, delta(11)-delta(33), range from 40 +/- 7 to 710 +/- 60 ppm; those determined for phosphorus range from 28 +/- 1.5 to 50 +/- 3 ppm. Values of (1)J((115)In,(31)P) range from 550 +/- 20 to 2500 +/- 20 Hz. For any given halide, the (1)J((115)In,(31)P) values generally increase with increasing basicity of the PR(3) ligand. Calculated values of (1)J((115)In,(31)P) and DeltaJ((115)In,(31)P) duplicate experimental trends and indicate that both the Fermi-contact and spin-dipolar Fermi-contact mechanisms make important contributions to the (1)J((115)In,(31)P) tensors. PMID- 20349957 TI - Effect of bridging position on the two-photon polymerization initiating efficiencies of novel coumarin/benzylidene cyclopentanone dyes. AB - One- and two-photon photophysical and photochemical properties of dyes 3-DAC and 4-DAC containing coumarin and benzylidene cyclopentanone moieties were studied. Their ground state configurations were optimized using both Hartree-Fock and density functional theory (B3LYP functional) methods, and excited-state properties were calculated using time-dependent density functional theory. These two dyes share the same formula and possess similar structures, except for different bridging positions between the benzylidene cyclopentanone and coumarin moieties. The bridging position was found to have a significant effect on the electronic structure and photophysical and photochemical properties of the dyes. 3-DAC shows higher conjugation and is more planar than 4-DAC, and it exhibits a larger TPA cross section. In contrast, 4-DAC has a twisted conformation, exhibits a lower electron transfer free energy with initiator and shows higher sensitizing efficiencies in one-photon polymerization. Furthermore, the application potential of 3-DAC and 4-DAC in two-photon polymerization (TPP) was studied. Both dyes could be used directly as initiators in TPP. The TPP threshold energies of the corresponding resins were as low as the best reported results. High-resolution 2D and 3D nanopatterns containing low amounts of small molecule residue were successfully fabricated by TPP, demonstrating the extensive application prospects of these dyes in the fabrication of micromachines, microsensor arrays and biomedical devices. PMID- 20349958 TI - A thieno[3,4-c]pyrrole-4,6-dione-based copolymer for efficient solar cells. AB - A new low-band-gap thieno[3,4-c]pyrrole-4,6-dione-based copolymer, PBDTTPD, has been designed and synthesized. PBDTTPD is soluble in chloroform or o dichlorobenzene upon heating and shows a broad absorption in the visible region. The HOMO and LUMO energy levels were estimated to be at -5.56 and -3.75 eV, respectively. These electrochemical measurements fit well with an optical bandgap of 1.8 eV. When blended with PC(71)BM, this polymer demonstrated a power conversion efficiency of 5.5% in a bulk-heterojunction photovoltaic device having an active area of 1.0 cm(2). PMID- 20349959 TI - Oxetanes in drug discovery: structural and synthetic insights. AB - An oxetane can trigger profound changes in aqueous solubility, lipophilicity, metabolic stability, and conformational preference when replacing commonly employed functionalities such as gem-dimethyl or carbonyl groups. The magnitude of these changes depends on the structural context. Thus, by substitution of a gem-dimethyl group with an oxetane, aqueous solubility may increase by a factor of 4 to more than 4000 while reducing the rate of metabolic degradation in most cases. The incorporation of an oxetane into an aliphatic chain can cause conformational changes favoring synclinal rather than antiplanar arrangements of the chain. Additionally spirocyclic oxetanes (e.g., 2-oxa-6-aza spiro[3.3]heptane) bear remarkable analogies to commonly used fragments in drug discovery, such as morpholine, and are even able to supplant the latter in its solubilizing ability. A rich chemistry of oxetan-3-one and derived Michael acceptors provide venues for the preparation of a broad variety of novel oxetanes not previously documented, thus providing the foundation for their broad use in chemistry and drug discovery. PMID- 20349960 TI - Design, synthesis and insecticidal activity of novel phenylpyrazoles containing a 2,2,2-trichloro-1-alkoxyethyl moiety. AB - A series of novel phenylpyrazoles containing a 2,2,2-trichloro-1-alkoxyethyl moiety were designed and synthesized via the key intermediate 5 trichloroethylideneimino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4 alkylsulfenylpyrazole (5). The addition reaction of the imine 5 was closely related with the nature of the alcohol. The target compounds were confirmed by (1)H NMR and elemental analysis. The results of bioassays indicated that the target compounds possessed excellent activities against a broad spectrum of insects such as bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens) and diamondback moth (Plutella xylostella). Especially, the foliar contact activity against bean aphid of compound 7h at 2.5 mg kg(-1) was 89%, the larvacidal activity against mosquito of compound 6c at 2.5 microg kg(-1) was 100%, the activity against diamondback moth of compound 7a at 5 mg kg(-1) was 87%, and all of these activities were much higher than the contrast ethiprole. The results of insecticidal activities showed that the two pairs of enantiomers 7d-1 and 7d-2 gave activities without distinctive difference, and it was the similar situation for 7e-1 and 7e-2. Interestingly, the target compounds exhibited high selectivity between diamondback moth and oriental armyworm, both of which are of the order Lepidoptera. The 2,2,2-trichloro-1-alkoxyethyl moiety was essential for high insecticidal activities. PMID- 20349961 TI - Overexpression of a cell wall enzyme reduces xyloglucan depolymerization and softening of transgenic tomato fruits. AB - Xyloglucan xyloglucosyltransferase/endohydrolase (XTHs: EC 2.4.1.207 and/or EC 3.2.1.151) has been proposed to have a dual role integrating newly secreted xyloglucan chains into an existing wall-bound xyloglucan and restructuring existing cell wall material by catalyzing transglucosylation between previously wall bound xyloglucan molecules. In this work we generated transgenic tomatoes with altered levels of an XTH gene. These transgenic fruits showed significant overexpression of the XTH proteins in comparison with the wild type. Specific XET activity was approximately 4.33 fold higher in the transgenic fruits compared with the wild type fruits, although in both cases the activity decreased during fruit development. Cell wall hemicelluloses extracted with 24% KOH showed a depolymerization of total sugar and xyloglucan during ripening, although this depolymerization was much lower in the transgenic than in the wild type tomatoes. These results suggest that the increased XET activity in the transgenic plants was responsible for the lower xyloglucan depolymerization. Fruit softening, during ripening, was lower in the transgenic tomatoes, indicating that the xyloglucan structure is related with the softening mechanism and that XET is one of the enzymes involved in the process. We suggest that the role of XET during fruit growth and ripening could be related to the maintenance of the structural integrity of the cell wall and the decrease in activity during ripening might contribute to the fruit softening. PMID- 20349962 TI - Comprehensive profiling of isoflavones, phytosterols, tocopherols, minerals, crude protein, lipid, and sugar during soybean (Glycine max) germination. AB - Isoflavone, phytosterol, tocopherol, mineral, protein, lipid, and sugar contents of soybeans were analyzed during 7-day germination with or without exposure to light. The levels of phytosterols and tocopherols increased significantly during the 3 day germination. Although malonyl glycosides were the predominant forms of isoflavones in soybean seeds, 77% of malonyl daidzin and 30% of malonyl genistin were converted to corresponding daidzin, daidzein, genistin, and genistein during the germination period. Slight decreases in malonal glycidin and malonyl glycidin concentrations were also observed while the total molar concentration of isoflavones remained constant. An increase of approximately 4% in the protein level was accompanied by a 5-6% reduction in the carbohydrate and lipid contents after the 7-day germination. Mineral (Ca, Cr, Fe, Zn Cu, K, Mg, Mn) levels did not vary much during germination, and the presence of light during germination had only a little, if any, effect on the levels of the micro- and macronutrients in soybeans. PMID- 20349963 TI - Mango extracts and the mango component mangiferin promote endothelial cell migration. AB - This study tested the hypothesis that mango extracts contain bioactive molecules capable of modulating endothelial cell migration, an essential step in the formation of new blood vessels or angiogenesis. The formation of new blood vessels is an important therapeutic target for diseases such as limb ischemia, coronary infarction or stroke. We examined the effect of mango peel and flesh extracts as well as the individual polyphenolic molecules, mangiferin and quercetin, on bovine aortic cell migration using a modified Boyden chamber assay. Our results show that mangiferin, and extracts rich in mangiferin, increase endothelial cell migration. The dose-effect relationship for various extracts further suggests that this action of mangiferin is modulated by other components present in the extracts. The promigratory effect of mango extracts or mangiferin was unrelated to an effect on cell proliferation, and did not involve a change in the production of matrix metalloprotease-2 or -9 by the endothelial cells. Taken together, these results suggest that mangiferin present in mango extracts may have health promoting effects in diseases related to the impaired formation of new blood vessels. PMID- 20349964 TI - Effect of heat treatment on the quantitative detection of egg protein residues by commercial enzyme-linked immunosorbent assay test kits. AB - This study examined the changes in the solubility of egg proteins as affected by different heat treatments and compared the performances of three commercial test kits for the quantitation of protein residues in heat-treated samples. National Institute of Standards and Technology (NIST) whole egg standard reference material #8415 and Henningsen spray-dried whole egg powder were subjected to heating in the presence of water at 60 and 100 degrees C, autoclaving for 5 or 10 min, or dry heating at 60-400 degrees C for 10 min. The amount of protein in the heated samples was assayed using the bicinchoninic acid total protein assay as well as egg-specific commercial enzyme-linked immunosorbent assay (ELISA) kits. Elevated heat resulted in a lower level of proteins extracted. Neogen's Veratox kit, which is reactive to multiple proteins in egg, greatly underestimated the amount of residual proteins in the boiled or autoclaved samples. Tepnel BioSystems' Biokits assay, which employs antibodies specific to a heat-stable marker protein (ovomucoid), registered a higher level of protein in these samples. Both test kits substantially underestimated the amount of residual proteins in samples dry-heated at temperatures >176 degrees C. The Morinaga test, using an improved extraction buffer, registered the highest level of protein in the heat-treated NIST samples but not the Henningsen samples. The underestimation by the commercial test kits was attributed to changes in the immunoreactivity of residual proteins after heat treatments and not the differences in the amount of protein extracted. These results suggest that thermal processing may affect the quantitative analysis of allergens and needs to be taken into account in the validation of commercial ELISA test kits. PMID- 20349966 TI - Excited state distortion in photochromic ruthenium sulfoxide complexes. AB - A series of photochromic ruthenium sulfoxide complexes of the form [Ru(bpy)(2)(OSOR)](+), where bpy is 2,2'-bipyridine and OSOR is 2 (benzylsulfinyl)benzoate (OSOBn), 2-(napthalen-2-yl-methylsulfinyl)-benzoate (OSONap), or 2-(pentafluorophenylmethanesulfinyl)benzoate (OSOBnF(5)), have been synthesized and characterized. In aggregate, the data are consistent with phototriggered isomerization of the sulfoxide from S-bonded to O-bonded. The S bonded complexes feature (3)MLCT absorption maxima at 388 nm (R = BnF(5)), 396 nm (R = Bn), and 400 nm (R = Nap). Upon charge transfer excitation the S-bonded peak diminishes concomitant with new peaks growing in at approximately 350 and approximately 495 nm. Spectroscopic and electrochemical data suggest that the electronic character of the substituent on the sulfur affects the properties of the S-bonded complexes, but not the O-bonded complexes. The isomerization is reversible in methanol solutions and, in the absence of light, thermally reverts to the S-bonded isomer with biexponential kinetics. The quantum yields of isomerization (Phi(s-->o)) were found to be 0.32, 0.22, and 0.16 for the R = BnF(5), Bn, and Nap complexes, respectively. Kinetic analyses of femtosecond transient absorption data were consistent with a nonadiabatic mechanism in which isomerization occurs from a thermally relaxed (3)MLCT state of S-bonded (or eta(2)-sulfoxide) character directly to the singlet O-bonded ground state. The time constants of isomerization (tau(s-->o)) were found to be 84, 291, and 427 ps for the R = BnF(5), Bn, and Nap complexes, respectively. Analysis of room temperature absorption and 77 K emission spectra reveal significant distortion between the S-bonded ground state ((1)GS(S)) and singlet metal-to-ligand charge transfer state ((1)MLCT(S)) and thermally relaxed (3)MLCT, respectively. The distortion is primarily attributed to low frequency metal-ligand and S horizontal lineO vibrational modes, which are intrinsically involved in the isomerization pathway. PMID- 20349965 TI - Polycation-induced cell membrane permeability does not enhance cellular uptake or expression efficiency of delivered DNA. AB - Polycationic materials commonly used to delivery DNA to cells are known to induce cell membrane porosity in a charge-density dependent manner. It has been suggested that these pores may provide a mode of entry of the polymer-DNA complexes (polyplexes) into cells. To examine the correlation between membrane permeability and biological activity, we used two-color flow cytometry on two mammalian cell lines to simultaneously measure gene expression of a plasmid DNA delivered with four common nonviral vectors and cellular uptake of normally excluded fluorescent dye molecules of two different sizes, 668 Da and 2 MDa. We also followed gene expression in cells sorted based on the retention of endogenous fluorescein. We have found that cell membrane porosity caused by polycationic vectors does not enhance internalization or gene expression. Based on this single-cell study, membrane permeability is found to be an unwanted side effect that limits transfection efficiency, possibly through leakage of the delivered nucleic acid through the pores prior to transcription and translation and/or activation of cell defense mechanisms that restrict transgene expression. PMID- 20349967 TI - Fluorinated colloidal emulsion of photochangeable rheological behavior as a sacrificial agent to fabricate organic, three-dimensional microstructures. AB - Three-dimensional organic microfabrication, an emerging technology, faces the challenge of lacking a sacrificial agent (SA) to temporarily support the formation of microscale geometries, which can be removed after a microstructure is constructed. In this study, an ultradense oil-in-organofluorine colloidal emulsion with photopolymerizable submicrometer droplets (diameter approximately 500 nm) was prepared and used as the required SA. Upon exposure to light, the colloidal emulsion undergoes a significant rheological change, which hardens the emulsion and presents the molding/protecting function that an SA must have. Importantly, the emulsion includes a synthesized fluorophilic/fluorophobic block copolymer surfactant to stabilize the droplet compartments, facilitating the dissolution of the postexposure SA. Two successfully built, complex, organic 3D microstructures show the effectiveness of using this novel SA material. PMID- 20349968 TI - Biocompatible graphene oxide-based glucose biosensors. AB - This letter demonstrates that a novel, highly efficient enzyme electrode can be directly obtained using covalent attachment between carboxyl acid groups of graphene oxide sheets and amines of glucose oxidase. The resulting biosensor exhibits a broad linear range up to 28 mM x mm(-2) glucose with a sensitivity of 8.045 mA x cm(-2) x M(-1). The glucose oxidase-immobilized graphene oxide electrode also shows a reproducibility and a good storage stability, suggesting potentials for a wide range of practical applications. The biocompatibility of as synthesized graphene oxide nanosheets with human cells, especially retinal pigment epithelium (RPE) cells, was investigated for the first time in the present work. Microporous graphene oxide exhibits good biocompatibility and has potential advantages with respect to cell attachment and proliferation, leading to opportunities for using graphene-based biosensors for the clinical diagnosis. PMID- 20349969 TI - Fourth-order curvature energy model for the stability of bicontinuous inverted cubic phases in amphiphile-water systems. AB - The bicontinuous inverted cubic (Q(II)) phases of amphiphiles in water have many practical applications. It is necessary to understand the stability of these phases as a function of composition and ambient conditions in order to make the best use of them. Moreover, many biomembrane lipids and some biomembrane lipid extracts form Q(II) phases. The stability of Q(II) phases in a given lipid composition is closely related to the susceptibility of that composition to membrane fusion: changes in composition that stabilize Q(II) phases usually increase the rate of membrane fusion. However, the factors determining Q(II) phase stability are not fully understood. Previously, an expression was derived for the curvature free energy of Q(II) phases with respect to that of the lamellar (L(alpha)) phase using a model for the curvature energy with terms up to fourth order in curvature as formulated by Mitov. Here this model is extended to account for the effects of water content on Q(II) phase stability. It is shown that the observed L(alpha)/Q(II) phase-transition temperature, transition enthalpy, and transition kinetics are all sensitive to water content. The same observables also become sensitive to small noncurvature energy contributions to the total free-energy difference between the Q(II) and L(alpha) phases, especially the unbinding energy in the L(alpha) phase. These predictions rationalize earlier observations of Q(II) phase formation in N-monomethylated dioleoylphosphatidylethanolamine that otherwise appear to be inconsistent. The model also provides a fundamental explanation of the hysteresis typically observed in transitions between the L(alpha) and Q(II) phases. It is an accurate model of Q(II) phase stability when the ratio of the volume fraction of the lipid in the Q(II) phase unit cell is < or = 0.5. PMID- 20349970 TI - Secondary structure in de novo designed peptides induced by electrostatic interaction with a lipid bilayer membrane. AB - We show that it is possible to induce a defined secondary structure in de novo designed peptides upon electrostatic attachment to negatively charged lipid bilayer vesicles without partitioning of the peptides into the membrane, and that the secondary structure can be varied via small changes in the primary amino acid sequence of the peptides. The peptides have a random-coil conformation in solution, and results from far-UV circular dichroism spectroscopy demonstrate that the structure induced by the interaction with silica nanoparticles is solely alpha-helical and also strongly pH-dependent. The present study shows that negatively charged vesicles, to which the peptides are electrostatically adsorbed via cationic amino acid residues, induce either alpha-helices or beta-sheets and that the conformation is dependent on both lipid composition and variations in peptide primary structure. The pH-dependence of the vesicle-induced peptide secondary structure is weak, which correlates well with small differences in the vesicles' electrophoretic mobility, and thus the surface charge, as the pH is varied. PMID- 20349971 TI - Probing one antiferromagnetic antiphase boundary and single magnetite domain using nanogap contacts. AB - We have probed one antiferromagnetic (AF) antiphase boundary (APB) and a single Fe(3)O(4) domain using nanogap contacts. Our experiments directly demonstrate that, in the case of probing one AF-APB, a large magnetoresistance (MR), high resistivity, and a high saturation field are observed as compared with the case of probing a single Fe(3)O(4) domain. The shape of the temperature-dependent MR curves is also found to differ between the single domain and one of the AF-APB measurements, with a characteristic strong temperature dependence for the single domain and temperature independence for the one AF-APB case. We argue that these observations are indicative of profound changes in the electronic transport across APBs. The investigated APB defects increase the activation energy and disturb the long-range charge ordering of monodomain Fe(3)O(4). PMID- 20349973 TI - Functionalization of oxide surfaces by terpyridine phosphonate ligands: surface reactions and anchoring geometry. AB - A strategy for creating a general-purposes surface functionalization platform is reported, based on direct attachment of phosphate groups onto hydroxylated surfaces and subsequent formation of a terpyridine-based monolayer. Such a platform is suitable for the construction, onto technologically relevant oxide surfaces, of single- and multilayer structures of interest in technological applications. In particular, the paper describes the successful attachment of 4 (2,2':6',2''-terpyridine-4-yl)benzenephosphonic acid (1, PPTP) onto a SiO(2) surface previously functionalized by means of Zr-phosphate groups. Two alternative anchoring strategies of the PPTP were explored: (i) a direct one-step way, implying no protection of terpyridinic functionality, and (ii) a three-step way, implying protection and successive deprotection of this group. It was found that, in the first case, the PPTP ligand anchoring to the Zr-containing phosphate layer takes place by means of terpyridinic group. At variance of this, in the second case, due to the protection of the terpyridinic functionality, the anchoring process takes place through the phosphonic group, making the terpyridinic moiety available for further reactions, i.e., multilayer constructs. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to study the functionalized surfaces, providing information on coverage, chemical structure, and stoichiometry of the various functionalized layers and, among the others, clear evidence of the PPTP linkage and orientation. PMID- 20349972 TI - Depletion-induced shape and size selection of gold nanoparticles. AB - For nanoparticle-based technologies, efficient and rapid approaches that yield particles of high purity with a specific shape and size are critical to optimize the nanostructure-dependent optical, electrical, and magnetic properties, and not bias conclusions due to the existence of impurities. Notwithstanding the continual improvement of chemical methods for shaped nanoparticle synthesis, byproducts are inevitable. Separation of these impurities may be achieved, albeit inefficiently, through repeated centrifugation steps only when the sedimentation coefficient of the species shows sufficient contrast. We demonstrate a robust and efficient procedure of shape and size selection of Au nanoparticles (NPs) through the formation of reversible flocculates by surfactant micelle induced depletion interaction. Au NP flocculates form at a critical surfactant micelle molar concentration, C(m)* where the number of surfactant micelles is sufficient to induce an attractive potential energy between the Au NPs. Since the magnitude of this potential depends on the interparticle contact area of Au NPs, separation is achieved even for the NPs of the same mass with different shape by tuning the surfactant concentration and extracting flocculates from the sediment by centrifugation or gravitational sedimentation. The refined NPs are redispersed by subsequently decreasing the surfactant concentration to reduce the effective attractive potential. These concepts provide a robust method to improve the quality of large scale synthetic approaches of a diverse array of NPs, as well as fine-tune interparticle interactions for directed assembly, both crucial challenges to the continual realization of the broad technological potential of monodispersed NPs. PMID- 20349975 TI - Detection of TrkB receptors distributed in cultured hippocampal neurons through bioconjugation between highly luminescent (quantum dot-neutravidin) and (biotinylated anti-TrkB antibody) on neurons by combined atomic force microscope and confocal laser scanning microscope. AB - We developed highly luminescent and cost-effective quantum dot (QD)-neutravidin (NTV) bioconjugates to detect the tyrosine kinase B (TrkB) receptors distributed in the cultured hippocampus neurons. Hippocampal neurons were incubated with biotinylated anti-TrkB antibody, followed by further incubation with QD-NTV bioconjugates. QD-NTV biomarkers on the extracellular domain of TrkB receptors were imaged by the combined atomic force microscope and confocal laser scanning microscope (AFM-CLSM) providing resolved (nanometer-scale) structural and fluorescent images. We found that TrkB receptors were distributed over the neuronal cell bodies (soma) and neurites. TrkB receptors in the somata looked more concentrated, but those in the neurites appeared punctate. Thus, our QD based immunocytochemistry technique combined with an AFM-CLSM can be used for three-dimensional morphology of neurons on nanometer-scale structural resolution and their fluorescence images with QDs. Furthermore, this technique can be applied for real-time fluorescence imaging or long-term study of live neurons. PMID- 20349976 TI - Nanoscaled polyion complex micelles for targeted delivery of recombinant hirudin to platelets based on cationic copolymer. AB - Polyion complex (PIC) micelles based on methoxy poly(ethylene glycol)-grafted chitosan (mPEG-g-chitosan) and Arg-Gly-Asp conjugated poly(ethylene glycol) grafted-chitosan (RGD-PEG-g-chitosan) were designed as carriers for platelet targeted delivery of recombinant hirudin variant-2 (rHV2). The rHV2-loaded plain PIC micelles (mPIC micelles) and RGD conjugated PIC micelles (RGD-PIC micelles) were successfully prepared with mean size of 30.9 +/- 0.5 nm and 41.9 +/- 1.8 nm, and their encapsulation efficiencies were 76.90 +/- 0.84% and 81.08 +/- 0.85%, respectively. The pharmacokinetics experiments showed that the mean retention time (MRT) of rHV2 encapsulated in both kinds of micelles was significantly prolonged, especially for mPIC micelles. The confocal laser scanning microscopy intuitively proved the specific binding of RGD-PIC micelles to platelets. The efficacies of rHV2-loaded RGD-PIC micelles were greatly better than those of rHV2 loaded mPIC micelles and rHV2 solution in aspect of anticoagulation and inhibition of platelet aggregation. These results suggested platelet-targeting specificity of RGD-PIC micelles and that RGD-PIC micelles could potentially be used as a carrier for platelet-targeted delivery and long circulation of rHV2. PMID- 20349977 TI - Pharmacophore development and application toward the identification of novel, small-molecule autotaxin inhibitors. AB - Autotaxin (ATX) is a secreted glycoprotein with lysophospholipase D (LPLD) activity that generates the bioactive lipid lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Both ATX and LPA have been linked to the promotion and progression of cancer as well as cardiovascular disease and obesity. Despite the fact that ATX inhibitors have the potential to be useful chemotherapeutics for multiple indications, few examples of potent ATX inhibitors are described in the current literature. Here we describe the development of pharmacophore models for the inhibition of ATX by nonlipids and apply these tools to the discovery of additional ATX inhibitors using the NCI open chemical repository database. From this database of > 250,000 compounds, 168 candidate inhibitors were identified. Of these candidates, 106 were available for testing and 33 were identified as active (those that inhibited ATX activity by > or =50% at a single 10 microM concentration), a 31% hit rate. Five of these compounds had IC(50) < 1.5 microM and the most potent compound possessed a K(i) of 271 nM. PMID- 20349978 TI - Understanding the dynamics behind the photoisomerization of a light-driven fluorene molecular rotary motor. AB - Light-driven molecular rotary motors derived from chiral overcrowded alkenes represent a broad class of compounds for which photochemical rearrangements lead to large scale motion of one part of the molecule with respect to another. It is this motion/change in molecular shape that is employed in many of their applications. A key group in this class are the molecular rotary motors that undergo unidirectional light-driven rotation about a double bond through a series of photochemical and thermal steps. In the present contribution we report a combined quantum chemical and molecular dynamics study of the mechanism of the rotational cycle of the fluorene-based molecular rotary motor 9-(2,4,7-trimethyl 2,3-dihydro-1H-inden-1-ylidene)-9H-fluorene (1). The potential energy surfaces of the ground and excited singlet states of 1 were calculated, and it was found that conical intersections play a central role in the mechanism of photo conversion between the stable conformer of 1 and its metastable conformer. Molecular dynamics simulations indicate that the average lifetime of the fluorene motor in the excited state is 1.40 +/- 0.10 ps when starting from the stable conformer, which increases to 1.77 +/- 0.13 ps for the reverse photoisomerization. These simulations indicate that the quantum yield of photoisomerization of the stable conformer is 0.92, whereas it is only 0.40 for the reverse photoisomerization. For the first time, a theoretical understanding of the experimentally observed photostationary state of 1 is reported that provides a detailed picture of the photoisomerization dynamics in overcrowded alkene-based molecular motor 1. The analysis of the electronic structure of the fluorene molecular motor holds considerable implications for the design of molecular motors. Importantly, the role of pyramidalization and conical intersections offer new insight into the factors that dominate the photostationary state achieved in these systems. PMID- 20349979 TI - Calculating radiation exposures during use of (14)C-labeled nutrients, food components, and biopharmaceuticals to quantify metabolic behavior in humans. AB - (14)C has long been used as a tracer for quantifying the in vivo human metabolism of food components, biopharmaceuticals, and nutrients. Minute amounts (< or =1 x 10 (-18) mol) of (14)C can be measured with high-throughput (14)C-accelerator mass spectrometry (HT (14)C-AMS) in isolated chemical extracts of biological, biomedical, and environmental samples. Availability of in vivo human data sets using a (14)C tracer would enable current concepts of the metabolic behavior of food components, biopharmaceuticals, or nutrients to be organized into models suitable for quantitative hypothesis testing and determination of metabolic parameters. In vivo models are important for specification of intake levels for food components, biopharmaceuticals, and nutrients. Accurate estimation of the radiation exposure from ingested (14)C is an essential component of the experimental design. Therefore, this paper illustrates the calculation involved in determining the radiation exposure from a minute dose of orally administered (14)C-beta-carotene, (14)C-alpha-tocopherol, (14)C-lutein, and (14)C-folic acid from four prior experiments. The administered doses ranged from 36 to 100 nCi, and radiation exposure ranged from 0.12 to 5.2 microSv to whole body and from 0.2 to 3.4 microSv to liver with consideration of tissue weighting factor and fractional nutrient. In comparison, radiation exposure experienced during a 4 h airline flight across the United States at 37000 ft was 20 microSv. PMID- 20349980 TI - Carbamoylation of aryl halides by molybdenum or tungsten carbonyl amine complexes. AB - When aryl halide is treated with molybdenum carbonyl amine complex in the presence of base, carbamoylation proceeds to give amide in good yield. The proposed mechanism involves oxidative addition of aryl halide to molybdenum(0) complex, migratory insertion to carbon monoxide giving acyl(amino)molybdenum(II) or aryl(carbamoyl)molybdenum(II) intermediate, and reductive elimination of the amide. This method is simple and provides an alternative method to the conventional palladium-catalyzed amide formation using gaseous carbon monoxide. PMID- 20349981 TI - Unfolding of the [Cu2(1,3-bis(9-methyl-1,10-phenanthrolin-2-yl)propane)2]2+ helicate. Coupling of the chlorocarbon dehalogenation to the unfolding process. AB - A new helical dimeric copper(I) complex [Cu(2)(mphenpr)(2)](ClO(4))(2) where mphenpr is 1,3-bis(9-methyl-1,10-phenanthrolin-2-yl)propane has been prepared and characterized by X-ray crystallography and NMR. In the solid state, the metal centers are 6.42 A apart, and the electronic structure has been investigated with use of density functional theory (DFT) calculations. In solution the dimer equilibrates with a monomeric form [Cu(mphenpr)](ClO(4)), and the mechanism of unfolding of the dimer into monomer has been studied. In the presence of CCl(4), formation of the monomer is coupled to the reductive dehalogenation of the halocarbon. The mechanism of this process has been probed by the study of short lived potential reaction intermediates using fast kinetic pulse radiolysis techniques and comparisons with DFT calculations. The copper(II) product [Cu(mphenpr)Cl](ClO(4)) and an analogue [Cu(mphenpr)](ClO(4))(2) have been isolated and characterized by X-ray crystallography. PMID- 20349982 TI - Poly(glycoamidoamine) vehicles promote pDNA uptake through multiple routes and efficient gene expression via caveolae-mediated endocytosis. AB - The use of synthetic polymers for the delivery of nucleic acids holds considerable promise for understanding and treating disease at the molecular level. This work aims to decipher the cellular internalization mechanisms for a series of synthetic glycopolymer DNA delivery vehicles we have termed poly(glycoamidoamine)s (PGAAs). To this end, we have performed cellular delivery experiments in the presence of pharmacological endocytosis inhibitors. Confocal microscopy analysis showed colocalization of labeled pDNA in polyplexes with immunolabeled endocytic molecules to identify the cellular internalization pathways in HeLa cells. Direct membrane penetration was also investigated through various methods, including cellular energy depletion and leakage of a cytosolic enzyme from the cell. The data suggests that the cellular internalization of PGAA polyplexes occurs through a multifaceted internalization mechanism primarily involving caveolae, yet clathrin-coated vesicles and macropinosomes were also involved to a lesser degree. The primary mechanism that leads to efficient nuclear delivery and transgene expression appears to be caveolae/raft-mediated endocytosis. The cellular internalization pathways for PGAAs were not identical to those for polyethylenimine, illustrating that differences in the chemical structure of materials directly impacts the cellular internalization mechanisms. PMID- 20349983 TI - Sensitivity enhancement of separated local field experiments: application to membrane proteins. AB - Separated local field (SLF) experiments have been used for almost three decades to obtain structural information in solid-state NMR. These experiments resolve chemical shift anisotropy (CSA) from dipole-dipole interactions (dipolar couplings, DC) in isolated spin systems. Both CSA and DC data can be converted into orientational constraints to elucidate the secondary structure and topology of membrane proteins in oriented lipid bilayers. Here, we propose a new suite of sensitivity enhanced SLF pulse sequences to measure CSA and DC for aligned membrane proteins and liquid crystalline molecules that will decrease the time needed for data acquisition. We demonstrate the efficacy of these new sensitivity enhanced experiments using both a single crystal of N-acetyl leucine and a single pass membrane protein sarcolipin reconstituted in aligned lipid bicelles. These results lay the groundwork for the routine application of this methodology for studying the structure and topology of membrane proteins. PMID- 20349984 TI - Molecular basis of enrofloxacin translocation through OmpF, an outer membrane channel of Escherichia coli--when binding does not imply translocation. AB - The molecular pathway of enrofloxacin, a fluoroquinolone antibiotic, through the outer membrane channel OmpF of Escherichia coli is investigated. High-resolution ion current fluctuation analysis reveals a strong affinity for enrofloxacin to OmpF, the highest value ever recorded for an antibiotic-channel interaction. A single point mutation in the constriction zone of OmpF, replacing aspartic acid at the 113 position with asparagine (D113N), lowers the affinity to a level comparable to other antibiotics. All-atom molecular dynamics simulations allow rationalizing the translocation pathways: wild-type OmpF has two symmetric binding sites for enrofloxacin located at each channel entry separated by a large energy barrier in the center, which inhibits antibiotic translocation. In this particular case, our simulations suggest that the ion current blockages are caused by molecules occupying either one of these peripheral binding sites. Removal of the negative charge on position 113 removes the central barrier and shifts the two peripheral binding sites to a unique central site, which facilitates translocation. Fluorescence steady-state measurements agree with the different location of binding sites for wild-type OmpF and the mutant. Our results demonstrate how a single-point mutation of the porin, and the resulting intrachannel shift of the affinity site, may substantially modify translocation. PMID- 20349985 TI - Microwave spectrum, structural parameters, and quadrupole coupling for 1,2 dihydro-1,2-azaborine. AB - The first microwave spectrum for 1,2-dihydro-1,2-azaborine has been measured in the frequency range 7-18 GHz, providing accurate rotational constants and nitrogen and boron quadrupole coupling strengths for three isotopomers, H(6)C(4)(11)B(14)N, H(6)C(4)(10)B(14)N, and H(5)DC(4)(11)B(14)N. The measured rotational constants were used to accurately determine coordinates for the substituted atoms and provide sufficient data to determine most of the important structural parameters for this molecule. The spectra were obtained using a pulsed beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of (14)N, (11)B, and (10)B nuclear quadrupole hyperfine interactions. High-level ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The rotational constants for the parent compound are A = 5657.335(1), B = 5349.2807(5), and C = 2749.1281(4) MHz, yielding the inertial defect Delta(0) = 0.02 amu x A(2) for the ground-state structure. The observed near-zero and positive inertial defect clearly indicates that the molecular structure of 1,2-dihydro-1,2-azaborine is planar. The least-squares fit analysis to determine the azaborine ring structure yielded the experimental bond lengths and 2sigma errors R(B-N) = 1.45(3) A, R(B-C) = 1.51(1) A, and R(N-C) = 1.37(3) A for the ground-state structure. Interbond angles for the ring were also determined. An extended Townes-Dailey population analysis of the boron and nitrogen quadrupole coupling constants provided the valence p-electron occupancy p(c) = 0.3e for boron and p(c) = 1.3e for nitrogen. PMID- 20349986 TI - Molecular wheels as nanoporous materials: differing modes of gas diffusion through Ga10 and Ga18 wheels probed by hyperpolarized 129Xe NMR spectroscopy. AB - The study of crystals of molecular wheels as nanoporous materials is reported. Hyperpolarized (129)Xe NMR spectroscopy has been used to characterize the mode of molecular diffusion and Xe interactions within the supramolecular nanochannels formed upon crystallization of the molecular wheels [Ga(10)(OMe)(20)(O(2)CMe)(10)] and [Ga(18)(pd)(12)(pdH)(12)(O(2)CMe)(6)(NO(3))(6)](NO(3))(6). In agreement with expectations based on the collision diameter of the Xe atom relative to the differing internal diameters of the two types of gallium wheels, single-file diffusion occurs in the Ga(10) channels, whereas in the Ga(18) system the data are consistent with normal, Fickian diffusion. Information about the electronic environment inside the channels was probed by the Xe chemical shift. The interaction of the gas with the channel walls is found to be substantially stronger than the interaction in organic nanotubes and zeolites. The results establish the ability of crystals of molecular wheel compounds to function as a new class of porous nanotubular materials, and ones of a known and variable diameter, for studying the channel diameter dependence of molecular exchange and unidirectional diffusion on the micrometer length scale. PMID- 20349987 TI - Novel (glycerol)borate-based ionic liquids: an experimental and theoretical study. AB - A series of newly designed (glycerol)borate based ionic liquids were synthesized and characterized. The synthesis of these ionic liquids involves, first, the preparation of the bis(glycerol)boric acid(s) followed by neutralization with the appropriate base, [cat]OH. Ionic liquids bearing inorganic (Li(+), Na(+), K(+)) or organic cations have been prepared and characterized. The ability of the bis(glycerol)borate anions to undergo dissociation reaction in the presence of water, depending on cation nature, was investigated by NMR. Theoretical calculations were also performed to evaluate the relative stability of the possible bis(glycerol)borate isomers as nude ions or as ion pairs with Li(+), Na(+), and H(+). Important information about the structural features of H[Gly(2)B] useful to rationalize the chemical behavior have been obtained. PMID- 20349988 TI - Proteomic analysis of the oxidative stress response in Kluyveromyces lactis and effect of glutathione reductase depletion. AB - Yeasts are unicellular eukaryotes that provide useful models for studying the oxidative stress (OS) response. Most investigations to date have been performed on the fermentative Saccharomyces cerevisiae. The respiratory Kluyveromyces lactis is emerging as an alternative model. Our previous studies showed that glutathione reductase (Glr1) is an interesting point of difference in the OS response between the two yeasts. In the present study, using extensive proteomic analyses, the response to H(2)O(2) and its relationship to Glr1 were investigated in wild-type and glr1-deletion mutant K. lactis strains. We identified 46 proteins that showed modified expression after H(2)O(2) addition and 42 for which the change was Glr1-dependent. As expected, these proteins include a variety of antioxidant enzymes, chaperones, and oxidoreductases related to defense against OS and damage repair. They also include a number of proteins necessary for energy production and carbohydrate and amino acid metabolism. H(2)O(2) addition causes down-regulation of enzymes from the glycolytic pathway and Krebs cycle in wild type K. lactis, whereas glr1-deletion prevents this effect and actually causes up regulation of the glycolytic, Krebs cycle, and oxidative pentose phosphate pathways. To our knowledge, this is the first global proteomic analysis performed on K. lactis. PMID- 20349989 TI - Na(+):aspartate coupling stoichiometry in the glutamate transporter homologue Glt(Ph). AB - The Na(+) aspartate symporter Glt(Ph) from Pyrococcus horikoshii is the only member of the glutamate transporter family for which crystal structures have been determined. The cation:aspartate coupling stoichiometry is unknown, thus hampering the elucidation of the ion coupling mechanism. Here we measure transport of (22)Na(+) and [(14)C]aspartate in proteoliposomes containing purified Glt(Ph) and demonstrate that three Na(+) ions are symported with aspartate. PMID- 20349990 TI - Speciation and reactivity of Cisplatin in river water and seawater. AB - The adsorption of the cytostatic anticancer drug, cisplatin (cis PtCl(2)(NH(3))(2)), has been studied after its addition to suspensions of estuarine sediment in river water and seawater. After a 16 h reaction period, adsorption was significantly greater in river water (sediment-water distribution coefficient, K(D), of 400 mL g(-1)) than that in seawater (K(D) approximately 150 mL g(-1)) because of the ready aquation of cisplatin to the more reactive monoaquacisplatin (cis-PtCl(OH(2))(NH(3))(2)(+)) at low chloride ion concentrations. Adsorption in river water was enhanced (K(D) approximately 2000 mL g(-1)) by a 24 h period of preincubation in the aqueous phase in which aquation proceeded further. The effects of pH on adsorption were relatively small, presumably because protonation-deprotonation of the particle surface was accompanied by near-equivalent shifts in the charge of hydrolysis products of aquated cisplatin. Kinetic experiments revealed a period of slow protracted uptake (up to about 60 h), followed by gradual desorption in both river water and seawater. Results were interpreted in terms of the formation of monoaquacisplatin, its adsorption to the particle surface, and the subsequent desorption of undefined, unreactive species. Kinetic data were modeled with a sequence of pseudofirst-order reactions and fits were obtained with forward and reverse rate constants for aquation of 1.79 x 10(-5) and 1.84 x 10(-5) s(-1) in river water and 5.50 x 10(-6) and 5.84 x 10(-6) s(-1) in seawater, and adsorption and desorption rate constants of 1.75 x 10(-5) and 0.20 x 10(-5) s(-1) in river water and 0.98 x 10(-5) and 2.8 x 10(-5) s(-1) in seawater. Environmental conditions favoring the retention of cisplatin and its degradation products are low chloride ion concentrations, high turbidities, and long residence or transit times; dispersion of the drug is favored in saline, coastal waters. PMID- 20349991 TI - Si=X multiple bonding with four-coordinate silicon? Insights into the nature of the Si=O and Si=S double bonds in stable silanoic esters and related thioesters: a combined NMR spectroscopic and computational study. AB - The electronic structures and nature of silicon-chalcogen double bonds Si=X (X = O, S) with four-coordinate silicon in the unique silanoic silylester 2 and silanoic thioester 3 have been investigated for the first time, by (29)Si solid state NMR measurements and detailed DFT and ab initio calculations. (29)Si solid state NMR spectroscopy of the precursor silylene 1 was also carried out. The experimental and computational study of 2 and 3, which was also supported by a detailed computational study of smaller model systems with Si=O and Si=S bonds, provides a deeper understanding of the isotropic and tensor components of their NMR chemical shifts. The general agreement between the experimental NMR spectra and the calculations strongly support our previous NMR assignment deduced from experiment. The calculations revealed that in 2 delta((29)Si(=O))(iso) is shifted upfield relative to H(2)Si=O by as much as 175 ppm; the substituents are responsible for ca. 100 ppm of this shift, while the remaining upfield shift is caused by change in the coordination number from three to four at the Si=O moiety. The change in coordination number leads to a nearly cylindrical symmetry in the plane which is perpendicular to the Si=O molecular axis (delta(11) approximately delta(22)), in contrast to the significant anisotropy found in this plane in typical doubly bonded compounds. The change in r(Si=O) or in the degree of pyramidality at the Si=O center which accompanies the change in coordination number has practically no effect on the chemical shift. delta((29)Si(=S))(iso) in 3 is shifted downfield significantly relative to that in 2, and a similar trend is found in smaller models with Si=S vs those with Si=O subunits. This downfield shift can be explained by the smaller sigma-pi* energy difference in the Si=S bond, relative to that of the Si=O bond. The NMR measurements of 2 and 3 having a four-coordinate silicon-chalcogen moiety, and the calculations of their tensor components, their bond polarities, and their Wiberg bond indices revealed that the Si=X moieties in both 2 and 3 have a significant pi(Si=X) character; yet, in both molecules there is a substantial contribution from a zwitterionic Si(+)-X(-) resonance structure, which is more pronounced in 2. PMID- 20349992 TI - Effects of constant voltage on time evolution of propagating concentration polarization. AB - We extend the analytical theory of propagating concentration polarization (CP) to describe and compare the effects of constant-voltage versus constant-current conditions on the transient development of CP enrichment and depletion zones. We support our analysis with computational and experimental results. We find that at constant voltage, enrichment and depletion regions spread as t(1/2) as opposed to the previously observed t(1) scaling for constant current conditions. At low, constant voltages, the growth and propagation of CP zones can easily be misinterpreted as nonpropagating behavior. PMID- 20349993 TI - Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. AB - We present a liquid chromatography-mass spectrometry (LC-MS) method that capitalizes on the mass-resolving power of the orbitrap to enable sensitive and specific measurement of known and unanticipated metabolites in parallel, with a focus on water-soluble species involved in core metabolism. The reversed phase LC method, with a cycle time 25 min, involves a water-methanol gradient on a C18 column with tributylamine as the ion pairing agent. The MS portion involves full scans from 85 to 1000 m/z at 1 Hz and 100,000 resolution in negative ion mode on a stand alone orbitrap ("Exactive"). The median limit of detection, across 80 metabolite standards, was 5 ng/mL with the linear range typically >or=100-fold. For both standards and a cellular extract from Saccharomyces cerevisiae (Baker's yeast), the median inter-run relative standard deviation in peak intensity was 8%. In yeast exact, we detected 137 known compounds, whose (13)C-labeling patterns could also be tracked to probe metabolic flux. In yeast engineered to lack a gene of unknown function (YKL215C), we observed accumulation of an ion of m/z 128.0351, which we subsequently confirmed to be oxoproline, resulting in annotation of YKL215C as an oxoprolinase. These examples demonstrate the suitability of the present method for quantitative metabolomics, fluxomics, and discovery metabolite profiling. PMID- 20349994 TI - Super silyl stereo-directing groups for complete 1,5-syn and -anti stereoselectivities in the aldol reactions of beta-siloxy methyl ketones with aldehydes. AB - In this communication, we report that substrate-controlled 1,5-syn and -anti stereoinduction in the aldol reaction of beta-tris(trialkylsilyl)siloxy methyl ketones can be achieved with high diastereoselectivities. Tris(trialkylsilyl)silyl groups are easily prepared and play an important role in the selectivities of these reactions. Furthermore, all of the 1,3,5-triol stereoisomers can easily be prepared from beta-siloxy methyl ketones in no more than three steps. PMID- 20349995 TI - Electron-, proton-, and photon-induced spectroscopic changes in chromophore quencher tricarbonyl(2,2'-bipyridine)rhenium(I) complexes with 4,4' azobis(pyridine). AB - We report in this work the synthesis and characterization of new mono- and dinuclear complexes of formulas: [Re(bpy)(CO)(3)(4,4'-azpy)](CF(3)SO(3)), 1 (bpy = 2,2'-bipyridine, 4,4'-azpy = 4,4'-azobis(pyridine)); [(bpy)(CO)(3)Re(4,4' azpy)Ru(NH(3))(5)](PF(6))(3).CH(3)CN.6H(2)O, 2 and the heterodinuclear species [(bpy)(CO)(3)Re(4,4'-azpy)Ru(NH(3))(5)](4+), 3 (obtained in situ by electrochemical oxidation of 2). The molecular structure of 1 has been determined by X-ray diffraction. We also report the effect of controlled potential electrolysis, protonation, and light excitation on the absorption and emission properties of these complexes. In particular, complex 1, which is almost non emissive at room temperature, recovers luminescence either by reduction of coordinated 4,4'-azpy or by trans- to cis-photoisomerization. The detected emission of 1 at 77 K is due to decay from a Re --> bpy metal-to-ligand charge transfer excited state. Time dependent density functional theory calculations support the interpretation of the photophysical changes induced by external stimuli. PMID- 20349996 TI - A repurposing strategy identifies novel synergistic inhibitors of Plasmodium falciparum heat shock protein 90. AB - Malaria is responsible for 3 million deaths annually. Antimalarial drug resistance is widespread, and few novel, well-defined targets exist. A robotic high throughput screen (HTS) was performed using 4000 small molecules from a natural compound (Spectrum), pharmacologically active (Lopac), and Food and Drug Administration (FDA) approved drug library (Prestwick) for competitive inhibition of the ATP-binding (GHKL) domain of Plasmodium falciparum (Pf) Hsp90, a highly conserved chaperone. Hits were further screened for specificity based on differential inhibition of PfHsp90 in comparison to human (Hs) Hsp90. PfHsp90 specific inhibitors showed 50% inhibitory concentrations (IC(50)) in the nanomolar range when tested using a cell-based antimalarial validation assay. Three hits, identified as selective PfHsp90 inhibitors in the HTS, also demonstrated synergistic activity in the presence of the known antimalarial drug chloroquine. These data support PfHsp90 as a specific antimalarial target with potential for synergy with known antimalarials. PMID- 20349997 TI - Hand-held photometer based on liquid-core waveguide absorption detection for nanoliter-scale samples. AB - This paper reports a fully integrated hand-held photometer based on the liquid core waveguide (LCW) detection principle for nanoliter-scale samples. All components of the photometer including light-emitting diode (LED) light source, LCW flow cell, photodiode detector, dropper pump, electronic circuit, liquid crystal display screen, and battery were fully integrated into a small-sized (12 x 4.5 x 2.1 cm) instrument. A bent optical coupler was developed to conduct the detection light into or out of the LCW flow cell through its sidewall. This design allowed the sampling probe, input and output optical couplers, and LCW flow cell to be integrated in a single Teflon AF capillary, which significantly simplified system structure, improved working reliability, and reduced sample consumption. Two UV-LEDs were used as light source in the photometer to achieve dual wavelength detection at 260 and 280 nm, which was applied to assess on-site the quality and quantity of DNA samples. The effective optical path length of the photometer was approximately 15 mm with a sample consumption of only 350 nL. The potential of the photometer applied in point of care testing was also demonstrated in the measurement of total cholesterol in serum samples. PMID- 20349998 TI - Toward the synthetic control of the HOMO-LUMO gap in binuclear systems: insights from density functional calculations. AB - Computational methods based on density functional theory have been applied to address the design of tailored HOMO-LUMO gap bimetallic complexes. We focus our attention on the [Cp*Fe-(L)-FeCp*] system, where two ferrocenyl units are linked through the dianion of fused ring ligands such as pentalene, s-indacene, dicyclopenta-[b,g]-naphthalene, dicyclopenta-[b,i]-anthracene and dicyclopenta [b,l]-tetracene. Our DFT calculations on the title organometallic complexes suggest a controlled decrease in the HOMO-LUMO gap, which is desirable for studies on electron-transfer phenomena, as well as the design potential devices for molecular electronic purposes. PMID- 20349999 TI - Happy B-Earth day. PMID- 20350000 TI - Impact of nanoscale zero valent iron on geochemistry and microbial populations in trichloroethylene contaminated aquifer materials. AB - Nanoscale zerovalent iron (NZVI) particles are a promising technology for reducing trichloroethylene (TCE) contamination in the subsurface. Prior to injecting large quantities of nanoparticles into the groundwater it is important to understand what impact the particles will have on the geochemistry and indigenous microbial communities. Microbial populations are important not only for nutrient cycling, but also for contaminant remediation and heavy metal immobilization. Microcosms were used to determine the effects of NZVI addition on three different aquifer materials from TCE contaminated sites in Alameda Point, CA, Mancelona, MI, and Parris Island, SC. The oxidation and reduction potential of the microcosms consistently decreased by more than 400 mV when NZVI was added at 1.5 g/L concentrations. Sulfate concentrations decreased in the two coastal aquifer materials, and methane was observed in the presence of NZVI in Alameda Point microcosms, but not in the other two materials. Denaturing gradient gel electrophoresis (DGGE) showed significant shifts in Eubacterial diversity just after the Fe(0) was exhausted, and quantitative polymerase chain reaction (qPCR) analyses showed increases of the dissimilatory sulfite reductase gene (dsrA) and Archaeal 16s rRNA genes, indicating that reducing conditions and hydrogen created by NZVI stimulate both sulfate reducer and methanogen populations. Adding NZVI had no deleterious effect on total bacterial abundance in the microcosms. NZVI with a biodegradable polyaspartate coating increased bacterial populations by an order of magnitude relative to controls. The lack of broad bactericidal effect, combined with the stimulatory effect of polyaspartate coatings, has positive implications for NZVI field applications. PMID- 20350001 TI - Changes in mercury levels in Great Lakes fish between 1970s and 2007. AB - A number of initiatives have curtailed anthropogenic mercury emissions in North America over the last two decades; however, various factors, including long-range transport of global emissions, may complicate the response of fish mercury levels to remedial actions. Since the Great Lakes of North America are together the largest surface freshwater body in the world and are under the influence of many complicating factors, trends of mercury in fish from the Great Lakes can reflect the overall impact of mercury management actions at local, regional, and perhaps global scales. Here we present a comprehensive view of mercury trends in Canadian Great Lakes fish using two large (total 5807 samples), different (fillet and whole fish), and long-term (1970s-2007) monitoring data sets. The spatial differences in lake trout and walleye mercury levels during this period have generally been within a factor of 2-3 with Lakes Erie and Superior having the lowest and highest concentrations, respectively. These spatial differences have diminished in the recent years (2000-2007). The concentrations have generally declined over the three decades (mid-1970s to 2007); however, in recent years, the concentration trends are flat in Lake Ontario walleye and appear to be increasing in Lake Erie walleye. There was a mismatch in the Lake Ontario lake trout and walleye temporal trends, which shows the importance of considering more than one fish species for proper spatial/temporal trend assessments. PMID- 20350002 TI - Enzyme-based multiplexer and demultiplexer. AB - A digital 2-to-1 multiplexer and a 1-to-2 demultiplexer were mimicked by biocatalytic reactions involving concerted operation of several enzymes. Using glucose oxidase (GOx) and laccase (Lac) as the data input signals and variable pH as the addressing signal, ferrocyanide oxidation in the output channel was selectively activated by one from two inputs, thus mimicking the multiplexer operation. A demultiplexer based on the enzyme system composed of GOx, glucose dehydrogenase (GDH) and horseradish peroxidase (HRP) allowed selective activation of different output channels (oxidation of ferrocyanide or reduction of NAD(+)) by the glucose input. The selection of the output channel was controlled by the addressing input of NAD(+). The designed systems represent important novel components of future branched enzyme networks processing biochemical signals for biosensing and bioactuating. PMID- 20350003 TI - Characterizing the adsorption of peptides to TiO2 in aqueous solutions by liquid chromatography. AB - The interactions between titanium oxide (TiO(2)) and flexible peptides, decorated by amine, carboxyl, and phosphoserine functional groups, were characterized using analytical liquid chromatography with various loading and eluting solutions. This approach enabled discernment of the type of intermolecular interactions generated between the peptides and the metal oxide surfaces in addition to unraveling more subtle effects, specific ions, and oxide phase may have on the adsorption. The peptide presenting Lys residues adsorbed to the oxide surface in the presence of Tris buffer and eluted under conditions that indicated its binding via electrostatic interactions at physiological pH values. Upon adsorption to the oxide in the presence of phosphate buffer, the same peptide exhibited stronger electrostatic interactions with the surface, mediated by the buffer phosphate ions. In Tris-buffered saline (TBS), pH 7.4, as the adsorption medium, the peptide with the phosphoserine residues exhibited affinity indicative of coordinative binding to the titanium oxide, whereas a similar peptide decorated by carboxylate groups failed to adsorb. On the basis of differences in the interactions of these peptides with the TiO(2), the efficient separation of the two peptides was demonstrated. A basic amphiphilic peptide, composed mostly of Lys and Leu residues, was found to strongly adsorb to TiO(2) while in helical conformation only, demonstrating the strong impact the secondary structure may have on adsorption to the surface. The methodology presented in this study allows the elucidation of in situ binding mechanism and relative strengths to titanium oxide surfaces at conditions which resemble biologically relevant environments. PMID- 20350004 TI - Tripodal exTTF-CTV hosts for fullerenes. AB - A receptor for fullerenes featuring three exTTF units linked to a CTV scaffold is described. The exTTF-CTV host forms remarkably stable complexes with both C(60) (log K(a) = 5.3 +/- 0.2) and C(70) (log K(a) = 6.3 +/- 0.6). Light-induced ESR spectra demonstrate that intracomplex PET processes take place in solution. PMID- 20350005 TI - Identification of phenylsulfone-substituted quinoxaline (WYE-672) as a tissue selective liver X-receptor (LXR) agonist. AB - A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXRbeta in kidney HEK-293 cells but did not activate Gal4 LXRbeta fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXRbeta (IC(50) = 53 nM), it had little binding affinity for LXRalpha (IC(50) > 1.0 microM) and did not recruit any coactivator/corepressor peptides in the LXRalpha multiplex assay. However, compound 13 showed good agonism in THP-1 cells with respect to increasing ABCA1 gene expression and good potency on cholesterol efflux in THP-1 foam cells. In an eight-week lesion study in LDLR -/- mice, compound 13 showed reduction of aortic arch lesion progression and no plasma or hepatic triglyceride increase. These results suggest quinoxaline 13 may have an improved biological profile for potential use as a therapeutic agent. PMID- 20350006 TI - Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates. AB - Three conjugates based on dendrimer PAMAM generation five were synthesized and radiolabeled successfully. To investigate their tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and micro-SPECT imaging were evaluated, respectively. The conjugate of (99m)Tc labeled PEGylated dendrimer PAMAM folic acid conjugate ((99m)Tc-G5-Ac-pegFA-DTPA) shows much higher uptake in KB cancer cells and accumulated more in the tumor area than that of the other two conjugates. The uptake in KB cells depends on the incubation time. The results of in vivo biodistribution agree with the data obtained from micro-SPECT imaging. These studies show that PEGylation of PAMAM dendrimer folic acid conjugate improves the tumor targeting. Folate-conjugated dendrimer maybe developed to be potential radiopharmaceuticals and targeted drug delivery systems. PMID- 20350008 TI - Plasmon resonant enhancement of carbon monoxide catalysis. AB - Irradiating gold nanoparticles at their plasmon resonance frequency creates immense plasmonic charge and high temperatures, which can be used to drive catalytic reactions. By integrating strongly plasmonic nanoparticles with strongly catalytic metal oxides, significant enhancements in the catalytic activity can be achieved. Here, we study the plasmonically driven catalytic conversion of CO to CO(2) by irradiating Au nanoparticle/Fe(2)O(3) composites. The reaction rate of this composite greatly exceeds that of the Au nanoparticles or Fe(2)O(3) alone, indicating that this reaction is not driven solely by the thermal (plasmonic) heating of the gold nanoparticles but relies intimately on the interaction of these two materials. A comparison of the plasmonically driven catalytic reaction rate with that obtained under uniform heating shows an enhancement of at least 2 orders of magnitude. PMID- 20350007 TI - Semitransparent organic photovoltaic cells with laminated top electrode. AB - We demonstrate semitransparent small molecular weight organic photovoltaic cells using a laminated silver nanowire mesh as a transparent, conductive cathode layer. The lamination process does not damage the underlying solar cell and results in a transparent electrode with low sheet resistance and high optical transmittance without impacting photocurrent collection. The resulting semitransparent phthalocyanine/fullerene organic solar cell has a power conversion efficiency that is 57% of that of a device with a conventional metal cathode due to differences in optical absorption. PMID- 20350009 TI - Construction of metal-ligand-coordinated multilayers and their selective separation behavior. AB - In this article, a layer-by-layer (LbL)-assembled coordination multilayer on planar and 3D substrates was explored by the alternate deposition of a transition metal-containing polyelectrolyte and a ligand-containing polymer via the formation of complexes. The metal-ligand coordination between the building blocks of Co(2+)-exchanged poly(styrene sulfonate) (PSS) and poly(4-vinyl pyridine) (P4 VP) has been demonstrated using UV-vis, FTIR, and XPS. The film thickness, structure, and morphology as well as the wettability as a function of bilayer number have been systematically investigated by profilometry, SEM, AFM, and contact angle analyzers. For the purpose of separation applications, the metal ligand-coordinated multilayer was assembled on both flat sheet and hollow fiber polymeric porous substrates using a dynamic pressure-driven LbL technique. It was demonstrated that the LbL-assembled PSS(Co)(1/2)/P4 VP multilayer membrane had high dehydration performance with respect to different solvent-water mixtures; it also had aromatic compound permselectivity from aromatic-aliphatic hydrocarbons and water-softening capacity. Meanwhile, the successful assembly of multilayers on hollow fibers indicates that the dynamic pressure-driven LbL technique is a unique approach to the construction of multilayers on porous 3-D substrates. Therefore, the metal-ligand-coordinated self-assembly could emerge as a powerful technique for the preparation of a range of separation membranes in different types of modules. PMID- 20350011 TI - Macroporous polymer from core-shell particle-stabilized Pickering emulsions. AB - Poly(styrene-co-N-isopropylacrylamide) (PS-co-PNIPAM) core-shell particles were synthesized and used as particulate emulsifiers in the preparation of particle stabilized (Pickering) emulsions. Highly concentrated oil-in-water emulsions with an internal phase up to 80 vol % can be produced using PS-co-PNIPAM core-shell particles along as the emulsifiers in emulsions. The core-shell particles are adsorbed at the liquid interface, acting as a barrier against oil droplet coalescence. In addition, it is likely that excess particles simultaneously form a gel in the continuous phase to trap oil droplets in the gel matrix, in turn inhibiting creaming and phase inversion. Evaporation in air of such a core-shell particle-stabilized emulsion directly leads to porous membranes in the absence of chemical reactions. The pore walls of the final structures are densely packed with layers of the core-shell particles. This provides great flexibility to prepare functionalized porous materials for opening up new applications. PMID- 20350010 TI - Delicate modification of poly(dimethylsiloxane) ultrathin film by low-energy ion beam treatment for durable intermediate liquid crystal pretilt angles. AB - Long-term stability of intermediate liquid crystal pretilt angles on a poly(dimethylsiloxane) (PDMS) ultrathin film grafted onto a surface was realized simply and easily via low-energy ion beam (IB) treatment. The composition and surface energy of the thin film could be controlled by varying the low-energy IB treatment. This treatment results in the permanent chemical modification of the film surface, converting it from organic PDMS to a mixed layer of organic PDMS and inorganic silica. The partial transformation of a PDMS surface gives rise to the control of the pretilt angle via the formation of the inhomogeneous surface and the stabilization of the pretilt angle via the cross-linking reaction of broken chemical bonds through IB irradiation. As a result, a continuous variation of pretilt angles that maintained their initial value with long-term stability was obtained. Thus, the unique chemical transformation of the PDMS surface using IB treatment may allow for the production of durable intermediate liquid crystal pretilt angles. PMID- 20350012 TI - Pluronic block copolymer-mediated interactions of organic compounds with noble metal nanoparticles for SERS analysis. AB - The composite silver and gold nanoparticles (AgNPs and AuNPs) coated with nonionic amphiphilic block copolymers (Pluronics L121, F68, or F127) are prepared by their adsorption under critical micelle concentrations. It is found that Pluronics bind to the surface of metal NPs as a very thin film by the hydrophobic association through poly(propylene oxide) block of the copolymers. The modification increases the colloidal stability of NPs with increasing hydrophilic lipophilic balance of Pluronics in the order of L121, F127, and F68. In order to investigate the potentials of polymer coated noble metal NPs as surface-enhanced Raman spectroscopy (SERS) probes, fluorescent dyes and doxorubicin are used as model compounds. It is found that Pluronic component promotes the adsorption of these compounds on the composite NPs resulting in a considerable increase of Raman signal. This effect is attributed to increased concentration of the analyte molecules on the composite surface due to the hydrophobic and charge-charge interactions between the analytes and the Pluronic coat, and the stabilization of NPs by poly(ethylene oxide) blocks. The copolymer coated AgNPs show higher SERS activity than the counterparts prepared with AuNPs. Among the prepared composites, the AgNPs modified with Pluronic F127 containing extended poly(propylene oxide) and poly(ethylene oxide) blocks exhibit maximal Raman activity using rhodamine 6G (Rh6G) with a EF of 9.04 x 10(6). The results show that the developed Pluronic-based SERS probes can be used for sensitive and selective analysis of organic analytes. PMID- 20350013 TI - A versatile approach to fabricate ordered heterogeneous bull's-eye-like microstructure arrays. AB - In this paper, ordered heterogeneous bull's-eye-like microstructure arrays were fabricated through a simple two-step method on gold substrate with patterned self assemble monolayers (SAMs). First, we prepared ordered polymer dot arrays on the SAMs patterned gold substrate by SAMs-direct dewetting. Subsequently, by manipulating concentration-controlled dewetting process, ordered ring arrays were obtained on the dot arrays patterned surface under the protection of water droplets. Namely, ordered bull's-eye-like structure arrays were fabricated successfully. The mechanism of these two kinds of dewetting process has been investigated in detail. And due to these two steps were independent, different materials could be simply introduced to the current system. Therefore, ordered homogeneous and heterogeneous bull's-eye-like structure arrays such as poly(N vinylcarbazole) (PVK) (dot)/PVK (ring), PVK/5,12-ditetradecylquinolino[2,3 b]acridine-7,14(5H,12H)-dione (DTQA), and PVK/Fe(3)O(4) nanoparticles were obtained. This straightforward method may open up new possibilities for practical use of microchips with binary heterogeneous structure arrays. PMID- 20350014 TI - Introduction to the special issue on diversity and leadership. AB - Theories of leadership have neglected diversity issues. As the population within the United States and in countries throughout the world becomes increasingly diverse, the contexts in which leadership occurs within institutions and communities will also become increasingly diverse. Attention to diversity is not simply about representation of leaders from diverse groups in the ranks of leadership. Attention to diversity means paradigm shifts in our theories of leadership so as to make them inclusive; it means incorporating explanations of how dimensions of diversity shape our understanding of leadership. It means paying attention to the perceptions and expectations of diverse leaders by diverse followers and to how bias influences the exercise of leadership. Although leadership theories have evolved and reflect changing social contexts, they remain silent on issues of equity, diversity, and social justice. Theories of leadership need to be expanded to incorporate diversity if they are to be relevant for the 21st century amidst new social contexts, emerging global concerns, and changing population demographics. PMID- 20350015 TI - Leadership: Why gender and culture matter. AB - For decades, understanding of leadership has been largely based on the results of studies carried out on White men in the United States. We review major theories and models of leadership as they pertain to either gender or culture. We focus on 3 approaches to leadership: trait (including leadership categorization or implicit leadership theory), behavioral (including the two-factor, transformational-transactional leadership, and leader-member exchange models), and contingency (i.e., contingency model of leadership effectiveness and normative decision making). We discuss how dynamics related to either culture or gender (e.g., stereotypes and schemas, ingroup-outgroup interaction, role expectations, power and status differentials) can have an important impact on many aspects of leadership. PMID- 20350016 TI - Women and women of color in leadership: complexity, identity, and intersectionality. AB - This article describes the challenges that women and women of color face in their quest to achieve and perform in leadership roles in work settings. We discuss the barriers that women encounter and specifically address the dimensions of gender and race and their impact on leadership. We identify the factors associated with gender evaluations of leaders and the stereotypes and other challenges faced by White women and women of color. We use ideas concerning identity and the intersection of multiple identities to understand the way in which gender mediates and shapes the experience of women in the workplace. We conclude with suggestions for research and theory development that may more fully capture the complex experience of women who serve as leaders. PMID- 20350017 TI - Women at the top: powerful leaders define success as work + family in a culture of gender. AB - How do women rise to the top of their professions when they also have significant family care responsibilities? This critical question has not been addressed by existing models of leadership. In a review of recent research, we explore an alternative model to the usual notion of a Western male as the prototypical leader. The model includes (a) relationship-oriented leadership traits, (b) the importance of teamwork and consensus building, and (c) an effective work-family interface that women with family care responsibilities create and use to break through the glass ceiling. We adopted a cross-cultural perspective to highlight the importance of relational orientation and work-family integration in collectivistic cultures, which supplements models of leadership based on Western men. Our expanded model of leadership operates in the context of a "culture of gender" that defines expectations for women and men as leaders. This complex model includes women in diverse global contexts and enriches our understanding of the interplay among personal attributes, processes, and environments in leadership. PMID- 20350018 TI - A two-dimensional model of intergroup leadership: the case of national diversity. AB - The model presented argues that leadership involves bringing together not only diverse individuals but also the subgroups to which they belong. The model further argues that this does not require replacing people's subgroup identities with a superordinate group identity (turning "us" and "them" into "we"); bringing together diverse individuals and their subgroups can be accomplished by promoting positive relations among subgroups, even as their distinctive identities (their senses of "us" and "them") remain. The model conceptualizes positive and negative intergroup attitudes as two independent dimensions of intergroup relations, each with distinct antecedents and distinct associated outcomes. Leaders seeking to create a collective from diverse subgroups must therefore (a) reduce negative intergroup attitudes and (b) increase positive intergroup attitudes. The author applies the model to organizational contexts of national diversity, but it can be applied to leadership across other forms of diversity. PMID- 20350019 TI - Toward an affirmative lesbian, gay, bisexual, and transgender leadership paradigm. AB - This article presents an affirmative paradigm for understanding the leadership of sexual minorities-that is, lesbian, gay, bisexual, and transgender (LGBT) people. Although research on LGBT issues in leadership to date is almost nonexistent, there are several bodies of literature that can contribute to an understanding of the unique leadership challenges faced by sexual minority people. These include the literatures on stigma and marginalization, leadership in particular status groups (e.g., college students, women), and LGBT vocational issues (especially workplace climate and identity disclosure). We propose a new, multidimensional model of LGBT leadership enactment that incorporates sexual orientation (particularly regarding identity disclosure), gender orientation (including leader gender), and the situation (conceptualized here as group composition); the model also is embedded in context, the most relevant factors that affect the enactment of leadership being stigma and marginalization. We explicate this model with findings and concepts from relevant literatures, and we conclude the article with recommendations for building a scholarly literature in LGBT leadership. PMID- 20350020 TI - Diversity and leadership in a changing world. AB - Scholars of leadership have infrequently addressed the diversity of leaders and followers in terms of culture, gender, race and ethnicity, or sexual orientation. This omission has weakened the ability of research and theory to address some of the most provocative aspects of contemporary leadership, including (a) the limited access of individuals from diverse identity groups to leadership roles; (b) the shaping of leaders' behavior by their dual identities as leaders and members of gender, racial, ethnic, or other identity groups; and (c) the potential of individuals from groups formerly excluded from leadership roles to provide excellent leadership because of their differences from traditional leaders. In addressing such issues, we argue that the joining of the two bodies of theory and research--one pertaining to leadership and the other to diversity- enriches both domains of knowledge and provides guidelines for optimizing leadership in contemporary organizations and nations. PMID- 20350021 TI - Obituary: Jack W. Brehm (1928-2009). PMID- 20350022 TI - Obituary: A. Toy Caldwell-Colbert (1951-2008). PMID- 20350023 TI - Obituary: Robert R. Zimmermann (1930-2009). PMID- 20350024 TI - Obituary: Erasmus (Bob) Hoch (1914-2008). PMID- 20350025 TI - Long-term effects of the family bereavement program on multiple indicators of grief in parentally bereaved children and adolescents. AB - OBJECTIVES: This article reports on results from a randomized experimental trial of the effects of the Family Bereavement Program (FBP) on multiple measures of grief experienced by parentally bereaved children and adolescents over a 6-year period. METHOD: Participants were 244 youths (ages 8-16, mean age = 11.4 years) from 156 families that had experienced the death of a parent. The sample consisted of 53% boys and 47% girls; ethnicity was 67% non-Hispanic White and 33% ethnic minority. Families were randomly assigned to the FBP (N = 135) or a literature control condition (N = 109). Two grief measures, the Texas Revised Inventory of Grief and the Intrusive Grief Thoughts Scale (IGTS) were administered at 4 times over 6 years: pretest, posttest, and 11-month and 6-year follow-ups. A 3rd measure, an adaptation of the Inventory of Traumatic Grief (ITG) was administered only at the 6-year follow-up. RESULTS: Compared with the control group, the FBP group showed a greater reduction in their level of problematic grief (IGTS) at posttest and 6-year follow-up and in the percentage at clinical levels of problematic grief at the posttest. The FBP also reduced scores on a dimension of the ITG, Social Detachment/Insecurity, at 6-year follow up for 3 subgroups: those who experienced lower levels of grief at program entry, older youths, and boys. CONCLUSION: These are the first findings from a randomized trial with long-term follow-up of the effects of a program to reduce problematic levels of grief of parentally bereaved youths. PMID- 20350026 TI - Youth psychotherapy change trajectories and outcomes in usual care: Community mental health versus managed care settings. AB - OBJECTIVE: The authors compared symptom change trajectories and treatment outcome categories in children and adolescents receiving routine outpatient mental health services in a public community mental health system and a private managed care organization. METHOD: Archival longitudinal outcome data from parents completing the Youth Outcome Questionnaire (Y-OQ) were retrieved for children and adolescents (4-17 years old) served in a community mental health system (n = 936, mean age = 12 years, 40% girls or young women, 28% from families of color) and a managed care organization (n = 3,075, mean age = 13 years, 45% girls or young women, race and ethnicity not reported). The authors analyzed Y-OQ data using multilevel modeling and partial proportional odds modeling to test for differences in change trajectories and final outcomes across the 2 service settings. RESULTS: Although initial symptom level was comparable across the 2 settings, the rate of change was significantly steeper for cases in the managed care setting. In addition, 24% of cases in the community mental health setting demonstrated a significant increase in symptoms over the course of treatment, compared with 14% of cases in the managed care setting. CONCLUSIONS: These results emphasize the need for increased attention to negative outcomes in routine mental health services and provide a stronger foundation for identifying youth cases at risk for treatment failure. In addition, given the overall differences observed across treatment settings for average rate of change and deterioration rates, results suggest that setting-specific model heuristics should be used for identifying cases at risk for negative outcomes. PMID- 20350027 TI - The effects of a multiyear universal social-emotional learning program: The role of student and school characteristics. AB - OBJECTIVE: This article examines the impact of a universal social-emotional learning program, the Fast Track PATHS (Promoting Alternative Thinking Strategies) curriculum and teacher consultation, embedded within the Fast Track selective prevention model. METHOD: The longitudinal analysis involved 2,937 children of multiple ethnicities who remained in the same intervention or control schools for Grades 1, 2, and 3. The study involved a clustered randomized controlled trial involving sets of schools randomized within 3 U.S. locations. Measures assessed teacher and peer reports of aggression, hyperactive-disruptive behaviors, and social competence. Beginning in first grade and through 3 successive years, teachers received training and support and implemented the PATHS curriculum in their classrooms. RESULTS: The study examined the main effects of intervention as well as how outcomes were affected by characteristics of the child (baseline level of problem behavior, gender) and by the school environment (student poverty). Modest positive effects of sustained program exposure included reduced aggression and increased prosocial behavior (according to both teacher and peer report) and improved academic engagement (according to teacher report). Peer report effects were moderated by gender, with significant effects only for boys. Most intervention effects were moderated by school environment, with effects stronger in less disadvantaged schools, and effects on aggression were larger in students who showed higher baseline levels of aggression. CONCLUSIONS: A major implication of the findings is that well implemented multiyear social-emotional learning programs can have significant and meaningful preventive effects on the population-level rates of aggression, social competence, and academic engagement in the elementary school years. PMID- 20350029 TI - Predicting outcome in computerized cognitive behavioral therapy for depression in primary care: A randomized trial. AB - OBJECTIVE: To explore pretreatment and short-term improvement variables as potential moderators and predictors of 12-month follow-up outcome of unsupported online computerized cognitive behavioral therapy (CCBT), usual care, and CCBT combined with usual care for depression. METHOD: Three hundred and three depressed patients were randomly allocated to (a) unsupported online CCBT, (b) treatment as usual (TAU), or (c) CCBT and TAU combined (CCBT&TAU). Potential predictors and moderators were demographic, clinical, cognitive, and short-term improvement variables. Outcomes were the Beck Depression Inventory-II score at 12 months of follow-up and reliable change. RESULTS: Those with higher levels of extreme (positive) responding had a better outcome in CCBT compared with TAU, whereas those having a parental psychiatric history or a major depressive disorder diagnosis had a better outcome in CCBT&TAU compared with TAU. Predictors regardless of treatment type included current employment, low pretreatment illness severity, and short-term improvement on clinical variables. CONCLUSIONS: Optimistic patients, holding approach-oriented coping strategies, might benefit most from CCBT, whereas CCBT&TAU might be the most suitable option for those with more severe vulnerability characteristics. Those with the least impairment improve the most, regardless of treatment type. PMID- 20350028 TI - The effect of mindfulness-based therapy on anxiety and depression: A meta analytic review. AB - OBJECTIVE: Although mindfulness-based therapy has become a popular treatment, little is known about its efficacy. Therefore, our objective was to conduct an effect size analysis of this popular intervention for anxiety and mood symptoms in clinical samples. METHOD: We conducted a literature search using PubMed, PsycINFO, the Cochrane Library, and manual searches. Our meta-analysis was based on 39 studies totaling 1,140 participants receiving mindfulness-based therapy for a range of conditions, including cancer, generalized anxiety disorder, depression, and other psychiatric or medical conditions. RESULTS: Effect size estimates suggest that mindfulness-based therapy was moderately effective for improving anxiety (Hedges's g = 0.63) and mood symptoms (Hedges's g = 0.59) from pre- to posttreatment in the overall sample. In patients with anxiety and mood disorders, this intervention was associated with effect sizes (Hedges's g) of 0.97 and 0.95 for improving anxiety and mood symptoms, respectively. These effect sizes were robust, were unrelated to publication year or number of treatment sessions, and were maintained over follow-up. CONCLUSIONS: These results suggest that mindfulness-based therapy is a promising intervention for treating anxiety and mood problems in clinical populations. PMID- 20350030 TI - Optimal levels of emotional arousal in experiential therapy of depression. AB - OBJECTIVE: To determine the relationship between length of time spent expressing highly aroused emotion and therapeutic outcome. METHOD: Thirty-eight clients (14 male, 24 female) between the ages of 22 and 60 years (M = 39.5, SD = 9.71), treated for depression with experiential therapy, were rated on working alliance and expressed emotional arousal (with the Client Expressed Emotional Arousal Scale) in their three highest arousal sessions. Among the clients, 34 were of European ethnicity, 2 were of Asian ethnicity, 1 was of Latino ethnicity, and 1 was of Caribbean-Canadian ethnicity. Clients were administered the short form of the Working Alliance Inventory following their 4th therapy session and also completed, pre- and posttherapy, the Beck Depression Inventory (BDI), the Global Severity Index (GSI) of the Symptom Checklist-90-Revised (SCL-90-R), the Inventory of Interpersonal Problems, and the Rosenberg Self-Esteem Scale. RESULTS: Hierarchical regressions showed that a nonlinear pattern of expressed emotional arousal predicted outcome significantly above the alliance. This combination predicted 30% of outcome variance on the BDI and 24% on the GSI (p < .01). An optimal frequency (25%) of highly aroused emotional expression was found to relate to outcome, with deviation from this optimal frequency predicting poorer outcome. CONCLUSIONS: Too much or too little emotion was found to be not as helpful as a moderate amount. It was concluded that expressed emotional arousal in experiential therapies has a more intricate relationship with therapeutic outcome than has previously been shown and that it is moderate amounts of heightened emotional arousal that improve predictions of therapeutic outcome. PMID- 20350031 TI - Therapist adherence/competence and treatment outcome: A meta-analytic review. AB - OBJECTIVE: The authors conducted a meta-analytic review of adherence-outcome and competence-outcome findings, and examined plausible moderators of these relations. METHOD: A computerized search of the PsycINFO database was conducted. In addition, the reference sections of all obtained studies were examined for any additional relevant articles or review chapters. The literature search identified 36 studies that met the inclusion criteria. RESULTS: R-type effect size estimates were derived from 32 adherence-outcome and 17 competence-outcome findings. Neither the mean weighted adherence-outcome (r = .02) nor competence-outcome (r = .07) effect size estimates were found to be significantly different from zero. Significant heterogeneity was observed across both the adherence-outcome and competence-outcome effect size estimates, suggesting that the individual studies were not all drawn from the same population. Moderator analyses revealed that larger competence-outcome effect size estimates were associated with studies that either targeted depression or did not control for the influence of the therapeutic alliance. CONCLUSIONS: One explanation for these results is that, among the treatment modalities represented in this review, therapist adherence and competence play little role in determining symptom change. However, given the significant heterogeneity observed across findings, mean effect sizes must be interpreted with caution. Factors that may account for the nonsignificant adherence-outcome and competence-outcome findings reported within many of the studies reviewed are addressed. Finally, the implication of these results and directions for future process research are discussed. PMID- 20350032 TI - Clinical consensus strategies for interpersonal problems between young adults and their parents. AB - OBJECTIVE: Research that identifies areas of agreement among expert therapists can complement findings from clinical trials by highlighting common practices as well as innovations. The present study accessed consensus among expert therapists on the effectiveness of clinical strategies for treating young adults experiencing interpersonal problems with their parents. METHOD: This study drew on the behavioral-analytic model (Goldfried & D'Zurilla, 1969) and the methodology of the Expert Consensus Guideline Series (Frances, Kahn, Carpenter, Ross, & Docherty, 1996). In Phase I, 54 therapists (mean age = 60.32 years; 55.6% women, 44.4% men; 96.3% White/European American) provided clinical situations involving young adult clients and their parents. In Phase II, 171 therapists (mean age = 59.45 years; 47.4% women, 52.0% men; 91.8% White/European American) proposed responses to the situations, and more general clinical strategies underlying the responses were identified. In Phase III, 134 peer-nominated expert therapists (a mean of 22.33 therapists per situation; mean age = 55.46 years; 61.2% women, 34.3% men; 91.0% White/European American) rated the effectiveness of these clinical strategies. RESULTS: Results indicated that the experts reached consensus on strategies rated as highly effective; in particular, they agreed on the value of exploring clients' emotional experience and providing validation. Participants reached greater agreement on strategies for use in future sessions than strategies for immediate use. Exploratory analyses revealed correlations between experts' theoretical orientations and their ratings. CONCLUSIONS: The findings provide converging evidence of the value of exploring emotions and validating clients and, further, demonstrate the feasibility of this method for accessing clinicians' experience. PMID- 20350033 TI - Marital status and satisfaction five years following a randomized clinical trial comparing traditional versus integrative behavioral couple therapy. AB - OBJECTIVE: To follow distressed married couples for 5 years after their participation in a randomized clinical trial. METHOD: A total of 134 chronically and seriously distressed married couples were randomly assigned to approximately 8 months of either traditional behavioral couple therapy (TBCT; Jacobson & Margolin, 1979) or integrative behavioral couple therapy (IBCT; Jacobson & Christensen, 1998). Marital status and satisfaction were assessed approximately every 3 months during treatment and every 6 months for 5 years after treatment. RESULTS: Pre- to posttreatment effect sizes on marital satisfaction were d = 0.90 for IBCT and d = 0.71 for TBCT, which were not significantly different. However, data through 2-year follow-ups revealed statistically significant superiority of IBCT over TBCT in relationship satisfaction, but subsequent data showed increasing similarity and nonsignificant differences in outcome. At 5-year follow up for marital satisfaction relative to pretreatment, effect sizes were d = 1.03 for IBCT and d = 0.92 for TBCT; 50.0% of IBCT couples and 45.9% of TBCT couples showed clinically significant improvement. Relationship status, obtained on all 134 couples, revealed that 25.7% of IBCT couples and 27.9% of TBCT couples were separated or divorced. These follow-up data compared favorably to other, long term results of couple therapy. CONCLUSION: TBCT and IBCT both produced substantial effect sizes in even seriously and chronically distressed couples. IBCT produced significantly but not dramatically superior outcomes through the first 2 years after treatment termination but without further intervention; outcomes for the 2 treatments converged over longer follow-up periods. PMID- 20350034 TI - Therapy processes and outcomes of psychological interventions for women diagnosed with gynecological cancers: A test of the generic process model of psychotherapy. AB - OBJECTIVE: Little attention has been paid to the role of nonspecific therapy processes in the efficacy of psychological interventions for individuals diagnosed with cancer. The goal of the current study was to examine the three constructs from the generic model of psychotherapy (GMP): therapeutic alliance, therapeutic realizations, and therapeutic openness/involvement in the treatment outcome of women with gynecological cancers attending either a 7-session supportive counseling intervention or a coping and communication skills intervention. METHOD: Two hundred and three women completed measures of alliance, realizations, and openness after Intervention Sessions 2, 3, and 6, as well as measures of depressive symptoms after these sessions and 6 months after the pre intervention assessment (posttreatment). RESULTS: Consistent with the GMP, in early sessions, therapeutic bond predicted openness in terms of positive affect experienced during sessions, and both aspects of openness (positive and negative affect), in turn, predicted more therapeutic realizations. Therapeutic realizations predicted perceptions of greater session progress, and greater therapeutic bond predicted more therapeutic realizations. When early session GMP variables were used to predict later GMP processes and outcomes and posttreatment outcomes, early therapeutic bond predicted later session therapeutic realizations directly and indirectly via emotional arousal, emotional arousal predicted session progress, session progress predicted lower postsession depressive symptoms, and depressive symptoms as rated after Session 6 predicted depressive symptoms 3 months posttreatment. However, a number of additional associations among GMP processes were found. CONCLUSIONS: Our results suggest that therapy processes played a role in predicting both short- and long-term treatment outcomes. PMID- 20350035 TI - Alcohol and sexual risk behaviors as mediators of the sexual victimization revictimization relationship. AB - OBJECTIVE: Women who experience sexual victimization, whether in childhood, adolescence, or adulthood, are at elevated risk of sexual revictimization. The mechanism responsible for this robust association is unclear, however. The present study proposed and tested a prospective, mediated model that posited that the association between adolescent and college victimization is mediated via 2 types of risk exposure in the first semester of college: alcohol-related and sexual risk behaviors. METHOD: Female adolescents (N = 469) were recruited from the community at the time of high school graduation. They completed baseline assessments as well as follow-ups at the end of the first and second semesters of college. RESULTS: Consistent with hypotheses, adolescent sexual victimization was associated indirectly, via high school risk behaviors, with increased first semester college risk behaviors (i.e., sexual partners, hookups, heavy episodic drinking, and heavy drinking contexts), which were, in turn, strongly predictive of sexual victimization experiences in the first year of college. College risk behaviors partially mediated the significant association between adolescent and first-year college victimization; however, even women without prior victimization faced elevated risk of college victimization with higher levels of college risk behaviors. CONCLUSIONS: Women who have experienced adolescent sexual victimization engage in higher levels of risk taking in college, thereby increasing vulnerability to college victimization. Intervention to reduce these primarily alcohol-related risk-taking behaviors may reduce vulnerability to college sexual victimization. PMID- 20350036 TI - The impact of perceived interpersonal functioning on treatment for adolescent depression: IPT-A versus treatment as usual in school-based health clinics. AB - OBJECTIVE: Aspects of depressed adolescents' perceived interpersonal functioning were examined as moderators of response to treatment among adolescents treated with interpersonal psychotherapy for depressed adolescents (IPT-A; Mufson, Dorta, Moreau, & Weissman, 2004) or treatment as usual (TAU) in school-based health clinics. METHOD: Sixty-three adolescents (12-18 years of age) participated in a clinical trial examining the effectiveness of IPT-A (Mufson, Dorta, Wickramaratne, et al., 2004). The sample was 84.1% female and 15.9% male (mean age = 14.67 years). Adolescents were 74.6% Latino, 14.3% African American, 1.6% Asian American, and 9.5% other. They came primarily from low-income families. Adolescents were randomly assigned to receive IPT-A or TAU delivered by school based mental health clinicians. Assessments, completed at baseline and at Weeks 4, 8, and 12 (or at early termination), included the Hamilton Rating Scale for Depression (Hamilton, 1967), the Conflict Behavior Questionnaire (Robin & Foster, 1989), and the Social Adjustment Scale-Self-Report (Weissman & Bothwell, 1976). RESULTS: Multilevel modeling indicated that treatment condition interacted with adolescents' baseline reports of conflict with their mothers and social dysfunction with friends to predict the trajectory of adolescents' depressive symptoms over the course of treatment, controlling for baseline levels of depression. The benefits of IPT-A over TAU were particularly strong for the adolescents who reported high levels of conflict with their mothers and social dysfunction with friends. CONCLUSIONS: Replication with larger samples would suggest that IPT-A may be particularly helpful for depressed adolescents who are reporting high levels of conflict with their mothers or interpersonal difficulties with friends. PMID- 20350037 TI - Prospective reciprocal relations between physical activity and depression in female adolescents. AB - OBJECTIVE: Although an inverse correlation between physical activity and depression among adolescents has been found in research, this relation has seldom been examined prospectively. Thus, we tested whether physical activity reduces risk for future escalations in depression and whether depression decreases likelihood of future change in physical activity. METHOD: Data from a longitudinal study involving annual assessments of 496 adolescent girls (mean age = 13 years, SD = 0.73) followed over a 6-year period were analyzed to address these questions. RESULTS: Using analyses that controlled for several covariates, we found that physical activity significantly reduced risk for future increases in depressive symptoms and risk for onset of major-minor depression. Further, depressive symptoms and major-minor depression significantly reduced future physical activity. However, predictive effects were modest for both. CONCLUSIONS: Results support a bidirectional relation between exercise and depression and imply that interventions that increase physical activity may reduce risk for depression among this high-risk population. PMID- 20350038 TI - Testing mediators of intervention effects in randomized controlled trials: An evaluation of three depression prevention programs. AB - OBJECTIVE: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. METHOD: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB bibliotherapy, or assessment-only control condition. RESULTS: The group CB intervention reduced depressive symptoms and negative cognitions and increased pleasant activities. Change in these mediators predicted change in depression, and intervention effects became weaker controlling for change in the mediators; yet, change in depression appeared typically to occur before change in the mediators. The supportive expressive intervention reduced depressive symptoms but affected only 1 of 2 mediators (emotional expression but not loneliness). Change in emotional expression did not correlate with change in depression, and change in depression usually occurred before change in the mediators. Bibliotherapy did not significantly affect depressive symptoms or the ostensive mediators (negative cognitions and pleasant activities), and change in depression usually occurred before change in the mediators. CONCLUSION: Results imply that this procedure provides a sensitive test of mediation but yielded limited support for the hypothesized mediators, suggesting that nonspecific factors may play an important mediational role. PMID- 20350039 TI - Long-term effects of the strong African American families program on youths' alcohol use. AB - OBJECTIVE: This report extends earlier accounts by addressing the effects of the Strong African American Families (SAAF) program across 65 months. Two hypotheses were tested: (a) Rural African American youths randomly assigned to participate in SAAF would demonstrate lower rates of alcohol use than would control youths more than 5 years later, and (b) SAAF's effects on deterring the onset of alcohol use in early adolescence would carry forward to mediate the program's long-term effects. METHOD: African American youths in rural Georgia (mean age at pretest = 10.8 years) were assigned randomly to the SAAF group (n = 369) or to a control group (n = 298). Past-month alcohol use was assessed at pretest and at 9, 18, 29, 53, and 65 months after pretest. RESULTS: SAAF participants increased their alcohol use at a slower rate than did adolescents in the control condition across the follow-up assessments. At the 65-month assessment, SAAF participants reported having drunk alcohol half as often as did youths in the control group. Consistent with the second hypothesis, SAAF's effects on deterring initiation carried forward to account for its effects on alcohol use across time. CONCLUSIONS: Training in protective parenting processes and self-regulatory skills during preadolescence may contribute to a self-sustaining trajectory of disinterest in and avoidance of alcohol use during adolescence when peers begin to model and sanction it. PMID- 20350040 TI - User settings of cue thresholds for binary categorization decisions. AB - The output of binary cuing systems, such as alerts or alarms, depends on the threshold setting-a parameter that is often user-adjustable. However, it is unknown if users are able to adequately adjust thresholds and what information may help them to do so. Two experiments tested threshold settings for a binary classification task based on binary cues. During the task, participants decided whether a product was intact or faulty. Experimental conditions differed in the information participants received: all participants were informed about a product's fault probability and the payoffs associated with decision outcomes; one third also received information regarding conditional probabilities for a fault when the system indicated or did not indicate the existence of one (predictive values); and another third received information about conditional probabilities for the system indicating a fault, in the instance of the existence or lack thereof, of an actual fault (diagnostic values). Threshold settings in all experimental groups were nonoptimal, with settings closest to the optimum with predictive-values information. Results corresponded with a model describing threshold settings as a function of the conditional probabilities for the different outcomes. From a practical perspective, results indicate that predictive-values information best supports decisions about threshold settings. Consequently, for users to adjust thresholds, they should receive information about predictive-values, provided that such values can be computed. PMID- 20350041 TI - Listener expertise and sound identification influence the categorization of environmental sounds. AB - The influence of listener's expertise and sound identification on the categorization of environmental sounds is reported in three studies. In Study 1, the causal uncertainty of 96 sounds was measured by counting the different causes described by 29 participants. In Study 2, 15 experts and 15 nonexperts classified a selection of 60 sounds and indicated the similarities they used. In Study 3, 38 participants indicated their confidence in identifying the sounds. Participants reported using either acoustical similarities or similarities of the causes of the sounds. Experts used acoustical similarity more often than nonexperts, who used the similarity of the cause of the sounds. Sounds with a low causal uncertainty were more often grouped together because of the similarities of the cause, whereas sounds with a high causal uncertainty were grouped together more often because of the acoustical similarities. The same conclusions were reached for identification confidence. This measure allowed the sound classification to be predicted, and is a straightforward method to determine the appropriate description of a sound. PMID- 20350042 TI - The effects of visual magnification and physical movement scale on the manipulation of a tool with indirect vision. AB - Modern tools often separate the visual and physical aspects of operation, requiring users to manipulate an instrument while viewing the results indirectly on a display. This can pose usability challenges particularly in applications, such as laparoscopic surgery, that require a high degree of movement precision. Magnification used to augment the view and, theoretically, enable finer movements, may introduce other visual-motor disruptions due to the apparent speed of the visual motion on screen (i.e., motion scaling). In this research, we sought to better understand the effects of visual magnification on human movement performance and control in operating a tool via indirect vision. Ten adult participants manipulated a computer mouse to direct a pointer to targets on a display. Results (Experiment 1) showed that, despite increased motion scaling, magnification of the view on screen enabled higher precision control of the mouse pointer. However, the relative effectiveness of visual magnification ultimately depended on the scale of the physical movement, and more specifically the precision limits of the whole-hand grip afforded by the mouse. When the physical scale of the hand/mouse movement was reduced (Experiment 2), fine-precision control began to reach its limits, even at full magnification. The role of magnification can thus be understood as "amplifying" the particular skill level afforded by the effecting limb. These findings suggest a fruitful area for future research is the optimization of hand-control interfaces of tools to maximize movement precision. PMID- 20350043 TI - Visualizing 3D objects from 2D cross sectional images displayed in-situ versus ex situ. AB - The present research investigates how mental visualization of a 3D object from 2D cross sectional images is influenced by displacing the images from the source object, as is customary in medical imaging. Three experiments were conducted to assess people's ability to integrate spatial information over a series of cross sectional images in order to visualize an object posed in 3D space. Participants used a hand-held tool to reveal a virtual rod as a sequence of cross-sectional images, which were displayed either directly in the space of exploration (in situ) or displaced to a remote screen (ex-situ). They manipulated a response stylus to match the virtual rod's pitch (vertical slant), yaw (horizontal slant), or both. Consistent with the hypothesis that spatial colocation of image and source object facilitates mental visualization, we found that although single dimensions of slant were judged accurately with both displays, judging pitch and yaw simultaneously produced differences in systematic error between in-situ and ex-situ displays. Ex-situ imaging also exhibited errors such that the magnitude of the response was approximately correct but the direction was reversed. Regression analysis indicated that the in-situ judgments were primarily based on spatiotemporal visualization, while the ex-situ judgments relied on an ad hoc, screen-based heuristic. These findings suggest that in-situ displays may be useful in clinical practice by reducing error and facilitating the ability of radiologists to visualize 3D anatomy from cross sectional images. PMID- 20350044 TI - Generalized "satisfaction of search": adverse influences on dual-target search accuracy. AB - The successful detection of a target in a radiological search can reduce the detectability of a second target, a phenomenon termed satisfaction of search (SOS). Given the potential consequences, here we investigate the generality of SOS with the goal of simultaneously informing radiology, cognitive psychology, and nonmedical searches such as airport luggage screening. Ten experiments utilizing nonmedical searches and untrained searchers suggest that SOS is affected by a diverse array of factors, including (1) the relative frequency of different target types, (2) external pressures (reward and time), and (3) expectations about the number of targets present. Collectively, these experiments indicate that SOS arises when searchers have a biased expectation about the low likelihood of specific targets or events, and when they are under pressure to perform efficiently. This first demonstration of SOS outside of radiology implicates a general heuristic applicable to many kinds of searches. In an example like airport luggage screening, the current data suggest that the detection of an easy-to-spot target (e.g., a water bottle) might reduce detection of a hard-to-spot target (e.g., a box cutter). PMID- 20350045 TI - Evolving and combining facial composites: between-witness and within-witness morphs compared. AB - Student participant-witnesses produced 4 composites of unfamiliar faces with a system that uses a genetic algorithm to evolve appearance of artificial faces. Morphs of 4 composites produced by different witnesses (between-witness morphs) were judged better likenesses (Experiment 1) and were more frequently named (Experiment 2) by participants who were familiar with the target actors than were morphs of 4 composites produced by a single witness (within-witness morphs). Within-witness morphs were judged better likenesses and more frequently named than the best or the first-produced individual composites. The same results for likeness judgments were observed after possible artifacts in the comparison of between- and within-witness morphs were eliminated (Experiment 3). Experiment 4 showed that both internal and external features were better represented in morphs than in the original composites, although the representation of internal features improved more. The results suggest that morphing improves the representation of faces by reducing random error. Between-witness morphs yield more benefit than within-witness morphs by reducing consistent but idiosyncratic errors of individual witnesses. The experiments provide the first demonstration of an advantage for within-witness morphs produced using a single system. Experiment 2 provides the first demonstration of a reliable advantage for between-witness morphs in the most forensically relevant task: naming a composite of a familiar person produced by a witness who was unfamiliar with the target. Morphing would enhance the recognition of facial composites of criminals. Within-witness morphing provides a methodology for use in crimes in which the victim is the only witness. PMID- 20350046 TI - Following your heart or your head: focusing on emotions versus information differentially influences the decisions of younger and older adults. AB - Research on aging has indicated that whereas deliberative cognitive processes decline with age, emotional processes are relatively spared. To examine the implications of these divergent trajectories in the context of health care choices, we investigated whether instructional manipulations emphasizing a focus on feelings or details would have differential effects on decision quality among younger and older adults. We presented 60 younger and 60 older adults with health care choices that required them to hold in mind and consider multiple pieces of information. Instructional manipulations in the emotion-focus condition asked participants to focus on their emotional reactions to the options, report their feelings about the options, and then make a choice. In the information-focus condition, participants were instructed to focus on the specific attributes, report the details about the options, and then make a choice. In a control condition, no directives were given. Manipulation checks indicated that the instructions were successful in eliciting different modes of processing. Decision quality data indicate that younger adults performed better in the information focus than in the control condition whereas older adults performed better in the emotion-focus and control conditions than in the information-focus condition. Findings support and extend extant theorizing on aging and decision making as well as suggest that interventions to improve decision-making quality should take the age of the decision maker into account. PMID- 20350047 TI - Sponsorship, ambushing, and counter-strategy: effects upon memory for sponsor and event. AB - Corporate sponsorship of sports, causes, and the arts has become a mainstream communications tool worldwide. The unique marketing opportunities associated with major events also attract nonsponsoring companies seeking to form associations with the event (ambushing). There are strategies available to brands and events which have been ambushed; however, there is only limited information about the effects of those strategies on attainment of sponsorship objectives. In Experiment 1, university staff and students participated by studying paragraphs linking a sponsor to a novel event. Relative to each sponsor-event pair, they then studied one of three different messages about a competitor. Results find a message which linked the competitor and the event increased competitor recall given the event as a cue and event recall given the competitor as a cue. These effects were moderated if there was information about the competitor not being the sponsor. In Experiment 2 ambushing and counter-ambushing information was presented over 2 days. Both types of messages increased competitor recall given the event as a cue and event recall given the competitor as a cue. In addition, "not sponsor" information was not always used even when it should have been recallable. The results can be explained if participants are using three cues: a specific cue such as a brand name, a contextual cue, and a category cue, such as the concept of an event. Findings suggest to sponsoring firms and event properties that counter-ambushing communications may have the unintended effect of strengthening an ambusher-event relationship in memory. PMID- 20350048 TI - Therapeutic potential of IL-27 in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by a diverse array of autoantibody production, complement activation and immune complex deposition, causing tissue and organ damage. Effective medical treatment for SLE is lacking because the etiology and pathogenesis of SLE are incompletely understood. It has been confirmed that cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including SLE. Recently, IL-27 was identified, which belongs to the IL-12 cytokine family. IL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models. In particular, suppressive effects on T(H)17 cells, which are implicated in the pathogenesis of SLE. Moreover, administration of IL-27 or augmentation of IL-27 signaling suppresses some autoimmune diseases, including autoimmune diabetes and murine lupus, suggesting that IL-27 may be therapeutically relevant in SLE. In this article, we discuss the biological features of IL-27 and summarize recent advances on the role of IL 27 in the pathogenesis and treatment of SLE. Even though IL-27 has shown therapeutic potential in SLE, further research, particularly in humans, is needed in order to establish the precise role of IL-27 in SLE. PMID- 20350049 TI - Circadian rhythms, adrenergic hormones and trafficking of hematopoietic stem cells. AB - IMPORTANCE OF THE FIELD: Under homeostasis, small numbers of haematopoietic stem cells (HSCs) are detectable in the bloodstream of mammals, but the mechanisms of their trafficking are unknown. AREAS COVERED IN THIS REVIEW: It has been shown that circulating HSCs exhibit marked circadian fluctuations due to standard cycles of 12 h light/12 h darkness. Circadian HSCs oscillations are strongly altered when mice are subjected to continuous light for two weeks or to a jet lag. In addition, circulating HSCs fluctuate in antiphase with the expression of the chemokine CXCL12 in the bone marrow microenvironment. Circadian HSC trafficking and expression of CXCL12 are modulated by core genes of the central clock through rhythmic secretion of adrenergic hormones from nerve terminals of the sympathetic nervous system (SNS) in the bone marrow. WHAT THE READER WILL GAIN: This review summarizes recent findings on the circadian regulation of HSC release in the bone marrow examining the molecular mechanisms through which the central molecular clock regulates CXCL12 in bone marrow stromal cells through rhythmic secretion of adrenergic hormones locally delivered in the bone marrow by nerve terminals from the SNS. TAKE HOME MESSAGE: The circadian HSCs trafficking during steady-state conditions, may promote the maintenance of haematopoiesis through the life of individuals. PMID- 20350050 TI - The apelinergic system: a promising therapeutic target. AB - IMPORTANCE OF THE FIELD: Apelin is a bioactive peptide known as the ligand of the G-protein-coupled receptor APJ. In recent years, there has been a growing body of evidence regarding the importance of apelin and APJ in the pathophysiology of cardiovascular, metabolic and gastrointestinal diseases, brain signalling, HIV infection and tumor angiogenesis. Therefore, the apelinergic system is involved in the pathogenesis of several diseases that represent a major burden to our society. AREAS COVERED IN THIS REVIEW: The goal of this paper is to give an up-to date review of existing information on apelin/APJ since the discovery of apelin in 1998, with particular focus on their involvement in the regulation of human body systems and potential therapeutic applications. WHAT THE READER WILL GAIN: An overview of the most important physiological functions of the apelinergic system and the diseases that may benefit in the future from its modulation as a therapeutic target. TAKE HOME MESSAGE: Today, the established biological effects of apelin involve major cardiovascular actions, neoangiogenesis, immunologic modulation and insulinemia control as well as body fluid and glucose homeostasis. However, the physiological and pathophysiological role of endogenous apelin is still unsettled and a better and profound knowledge of this system in humans is necessary for the development of novel apelinergic-based therapeutic targets. PMID- 20350051 TI - Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes. AB - The objective of this study was to investigate the interaction between glycyrrhizin and omeprazole and observe the effects of glycyrrhizin on CYP2C19 and CYP3A4 activities in healthy Chinese male volunteers with different CYP2C19 genotypes. Eighteen healthy subjects (six CYP2C19*1/*1, five CYP2C19*1/*2, one CYP2C19*1/*3, five CYP2C19*2/*2 and one CYP2C19*2/*3) were enrolled in a two phase randomized crossover trial. In each phase, all subjects received placebo or glycyrrhizin salt tablet 150 mg twice daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography. After 14 day treatment of glycyrrhizin, plasma omeprazole significantly decreased, and those of omeprazole sulfone significantly increased. However, plasma concenetrations of 5-hydroxyomeprazole did not significantly change. The ratio of AUC(0-infinity) of omeprazole to omeprazole sulfone decreased by 43.93% + or - 13.56% (p = 0.009) in CYP2C19*1/*1, 44.85% + or - 14.84% (p = 0.002) in CYP2C19*1/*2 or *3 and 36.16% + or - 7.52% (p < 0.001) in CYP2C19*2/*2 or *3 while those of omeprazole to 5-hydroxyomeprazole did not change significantly in all three genotypes. No significant differences in glycyrrhizin response were found among CYP2C19 genotypes. Glycyrrhizin induces CYP3A4-catalyzed sulfoxidation of omeprazole and leads to decreased omeprazole plasma concentrations, but has no significant impact on CYP2C19-dependent hydroxylation of omeprazole. PMID- 20350052 TI - Preparation and characterization of niosomes containing ribavirin for liver targeting. AB - The objectives of this research were to prepare ribavirin niosomes and evaluate the influence of niosomal encapsulation on drug liver targeting in rats. Ribavirin niosomes were prepared by the thin film hydration method using span 60, cholesterol, and dicetyl phosphate in molar ratios of (1:1:0), (4:2:0), (1:1:0.1), and (4:2:1). The prepared niosomes were characterized in vitro for vesicle size, drug entrapment, drug release profiles, and vesicular stability at refrigerator temperature. The results indicated that niosomes of the molar ratio (4:2:1) had a significantly (p < 0.05) higher entrapment percentage of ribavirin than the other molar ratios, moreover, they revealed sustained release characteristics as well as longer release pattern than other niosomal formulations. Accordingly, niosomes of molar ratio (4:2:1) was selected for in vivo liver targeting study. Separately, niosomal ribavirin dispersion and free ribavirin solution were administered as a single dose of 30 mg/kg by intraperitoneal injection into two groups of rats to compare the liver ribavirin concentration. The obtained results show that the niosomal formulation significantly increased ribavirin liver concentration (6-fold) in comparison with ribavirin-free solution. Based on the previous results, the use of niosomes as a drug delivery system for ribavirin has significant liver targeting properties, this is expected to improve the efficacy of low doses of ribavirin and minimize its toxic side-effects at higher doses. PMID- 20350053 TI - Pharmacokinetics of liquiritigenin and its two glucuronides, M1 and M2, in rats with acute hepatitis induced by d-galactosamine/lipopolysaccharide or CCl(4). AB - Cytoprotective effects of liquiritigenin (LQ) against liver injuries have been reported, but its pharmacokinetics has not been studied in acute hepatitis. Thus, pharmacokinetics of LQ and its two conjugated glucuronide metabolites: 4'-O glucuronide (M1) and 7-O-glucuronide (M2), in rats with acute hepatitis induced by d-galactosamine/lipopolysaccharide (GalN/LPS) rats or carbon tetrachloride treated (CCl(4)-treated) rats were evaluated. LQ was administered intravenously (20 mg kg(-1)) and orally (50 mg kg(-1)) to control GalN/LPS and CCl(4)-treated rats. Expression of uridine 5'-diphospho-glucuronosyltransferases 1A (UGT1A) and in vitro metabolism of LQ in hepatic and intestinal microsomes were also measured. After intravenous administration of LQ, area under the plasma concentration-time curve (AUC) of LQ in GalN/LPS rats was significantly smaller than that in controls due to faster non-renal clearance, as a result of its greater free fraction in plasma and faster hepatic blood flow rate than the controls. In CCl(4)-treated rats, the AUC(M1, 0-8 h)/AUC(LQ) and AUC(M2, 0-8 h)/AUC(LQ) ratios were significantly greater than the controls due to decrease in biliary excretion of M1 and M2. However, no significant pharmacokinetic changes were observed in both acute hepatitis rats after oral administration due to comparable intestinal metabolism of LQ. Modification of oral dosage regimen of LQ may not be necessary in patients with acute hepatitis; but human studies are required. PMID- 20350054 TI - Tailoring of locust bean gum and development of hydrogel beads for controlled oral delivery of glipizide. AB - In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1-5% w/v) of aluminum chloride (AlCl(3)) was utilized for the development of glipizide loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl(3) concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl(3) provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide. PMID- 20350055 TI - Inhalation devices for long-acting beta2-agonists: efficiency and ease of use of dry powder formoterol inhalers for use by patients with asthma and COPD. AB - BACKGROUND: Since the long-acting beta(2)-agonist bronchodilator, formoterol, first became available for the treatment of subjects with asthma or chronic obstructive pulmonary disease (COPD), generic forms of this agent have been launched in a variety of devices. It is timely to review the characteristics of the original dry powder delivery device, the single-dose Aerolizer, its in vitro performance and its comparability with other inhaler devices that are now available for delivery of formoterol. SCOPE: This review focuses on the performance of the formoterol Aerolizer inhaler in comparison with other inhalers. Publically available data (PubMed) on the device performance characteristics of the Aerolizer were reviewed and summarized, together with the results of comparative studies performed by the authors. Published studies (PubMed) on patient handling and inhaler technique that include the Aerolizer are described and studies comparing the clinical effect of formoterol in the Aerolizer with formoterol delivered via other devices were reviewed and are summarized. FINDINGS: The Aerolizer performs consistently in dosing efficiency across a range of inspiratory flow rates, suggesting its suitability for use by patients with differing inspiratory flow abilities. The single-dose, capsule based nature of the device provides patients with obvious feedback on whether the drug has been taken successfully and the Aerolizer has been shown to be one of the more easily used devices in comparative patient handling studies. Studies comparing the clinical effect of formoterol delivered by different inhalation devices show that formoterol via Aerolizer has an equivalent therapeutic effect. CONCLUSION: Judged on the basis of dosing efficiency, ease of use and clinical equivalence, formoterol Aerolizer remains a useful option in the management of patients with asthma or COPD. PMID- 20350056 TI - An interview with Robert S. Lane, Ph.D. Interviewed by Vicki Glaser. AB - Dr. Robert Lane received a B.A. degree in psychology from the University of California at Berkeley (UCB), an M.A. degree in biology at San Francisco State College, and a Ph.D. in entomology at UCB. While employed as a California State public health biologist he began his long-standing studies of the biology of ticks and the ecology and epidemiology of tick-borne disease agents. In 1984, Dr. Lane joined the faculty of UCB as a medical entomologist, a position he has held until the present. The diseases he and his many co-workers have investigated include Colorado tick fever, human granulocytic anaplasmosis, relapsing fever, Rocky Mountain spotted fever, tularemia, and particularly Lyme disease. Findings from these studies have elucidated the basic transmission cycles of and risk factors for spotted fever-group rickettsiae and Lyme disease spirochetes in the far western United States. Bob is a Fellow of both the California Academy of Sciences and the American Association for the Advancement of Science, a recipient of a UCB Biology Faculty Research Award and the C.W. Woodworth Award from the Pacific Branch of the Entomological Society of America, and a member of the Council for the International Congresses of Entomology. Also, he has served as president of the Acarological Society of America, the International Northwestern Conference on Diseases in Nature Communicable to Man, the Northern California Parasitologists, and the Society for Vector Ecology, as well as the Chair of Section D (Medical/Veterinary Entomology), Entomological Society. PMID- 20350057 TI - Effects of aging on hippocampal and anterior temporal activations during successful retrieval of memory for face-name associations. AB - Memory for face-name associations is an important type of memory in our daily lives, and often deteriorates in older adults. Although difficulty retrieving face-name associations is often apparent in the elderly, there is little neuroscientific evidence of age-related decline in this memory. The current fMRI study investigated differences in brain activations between healthy young and older adults during the successful retrieval of people's names (N) and job titles (J) associated with faces. During encoding, participants viewed unfamiliar faces, each paired with a job title and name. During retrieval, each learned face was presented with two job titles or two names, and participants were required to choose the correct job title or name. Retrieval success activity (RSA) was identified by comparing retrieval-phase activity for hits versus misses in N and J, and the RSAs in each task were compared between young and older adults. The study yielded three main findings. First, the hippocampus showed significant RSA in both tasks of N and J, and the activity was greater for young compared to older subjects. Second, the left anterior temporal lobe (ATL) showed greater RSA in N than in J, but there was no age difference in the activity in this region. Third, functional connectivity between hippocampal and ATL activities in both retrieval tasks was higher for young than for older adults. Taken together, age related differences in hippocampal activities and hippocampus-ATL connectivity could contribute to age-related decline in relational memory and to complaints of poor retrieval of people's names by older adults. PMID- 20350058 TI - Medial prefrontal cortex predicts intertemporal choice. AB - People often make shortsighted decisions to receive small benefits in the present rather than large benefits in the future, that is, to favor their current selves over their future selves. In two studies using fMRI, we demonstrated that people make such decisions in part because they fail to engage in the same degree of self-referential processing when thinking about their future selves. When participants predicted how much they would enjoy an event in the future, they showed less activity in brain regions associated with introspective self reference--such as the ventromedial pFC (vMPFC)--than when they predicted how much they would enjoy events in the present. Moreover, the magnitude of vMPFC reduction predicted the extent to which participants made shortsighted monetary decisions several weeks later. In light of recent findings that the vMPFC contributes to the ability to simulate future events from a first-person perspective, these data suggest that shortsighted decisions result in part from a failure to fully imagine the subjective experience of one's future self. PMID- 20350059 TI - A candidate for the attentional bottleneck: set-size specific modulation of the right TPJ during attentive enumeration. AB - Several recent behavioral studies have shown that the enumeration of a small number of items (a process termed subitizing) depends on the availability of attentional resources and is not a preattentive process as previously thought. Here we studied the neural correlates of visual enumeration under different attentional loads in a dual-task paradigm using fMRI. Relatively intact subitizing under low attentional load compared to impaired subitizing under high attentional load was associated with an increase in BOLD signal in the right temporo-parietal junction (rTPJ). Crucially, attentionally modulated response in the rTPJ was specific to small set sizes (up to 3 items) and did not occur at larger set sizes (5-7 items). This result has two implications: (1) Subitizing involves part of the fronto-parietal network for stimulus-driven attention providing neural evidence against preattentive subitizing. (2) Activity in rTPJ is set-size modulated. Together with similar evidence from studies probing visual short-term memory, this result suggests that rTPJ modulation might reflect the brain's ability to attentively handle small set sizes. Thus, the rTPJ may play an important role for the emergence of a capacity limit in both enumeration and visual short-term memory. PMID- 20350066 TI - From molecular mechanisms toward the cure of systemic amyloidoses. Abstracts of the XII International Symposium on Amyloidosis. April 18-21, 2010. Rome, Italy. PMID- 20350060 TI - Perceptual fusion tendency of speech sounds. AB - To discriminate and to recognize sound sources in a noisy, reverberant environment, listeners need to perceptually integrate the direct wave with the reflections of each sound source. It has been confirmed that perceptual fusion between direct and reflected waves of a speech sound helps listeners recognize this speech sound in a simulated reverberant environment with disrupting sound sources. When the delay between a direct sound wave and its reflected wave is sufficiently short, the two waves are perceptually fused into a single sound image as coming from the source location. Interestingly, compared with nonspeech sounds such as clicks and noise bursts, speech sounds have a much larger perceptual fusion tendency. This study investigated why the fusion tendency for speech sounds is so large. Here we show that when the temporal amplitude fluctuation of speech was artificially time reversed, a large perceptual fusion tendency of speech sounds disappeared, regardless of whether the speech acoustic carrier was in normal or reversed temporal order. Moreover, perceptual fusion of normal-order speech, but not that of time-reversed speech, was accompanied by increased coactivation of the attention-control-related, spatial-processing related, and speech-processing-related cortical areas. Thus, speech-like acoustic carriers modulated by speech amplitude fluctuation selectively activate a cortical network for top-down modulations of speech processing, leading to an enhancement of perceptual fusion of speech sounds. This mechanism represents a perceptual-grouping strategy for unmasking speech under adverse conditions. PMID- 20350068 TI - A Canadian model of work integration for persons with mental illnesses. AB - PURPOSE: The many programmes, services and policy initiatives that focus on work integration for persons with mental illnesses and psychiatric disabilities reflect a multitude of beliefs and practices that lead the field to work in divergent, sometimes conflicting directions. This article presents a framework of the central constructs that dominate the field of work integration and mental illness. METHOD: Using the principles of constructivist grounded theory, an analysis of Canadian documents was conducted; the sample was comprised of 100 academic publications, 76 government documents, 138 popular press, 5 legal papers and 107 documents from work initiatives across Canada. In addition, semi structured interviews were conducted with 19 key informants from across Canada. RESULTS: Five central perspectives were identified, around which the field of work integration currently operates: a competency perspective; a citizenship perspective; a workplace health perspective; a perspective focussing on potential, growth and self-construction; a community economic development perspective. CONCLUSIONS: Uncovering the varied discourses around work integration enables an understanding of the different ways in which the problem of work integration has come to be seen in today's context; how it is understood, spoken about, dealt with and internalised by individuals and groups. The framework sheds light on the rationale for the range of solutions that have been developed to address the problem of work integration, and it is useful in the analysis of how policy, practice and research initiatives are shaped and promoted. PMID- 20350070 TI - Vocal perfection in yodelling--pitch stabilities and transition times. AB - BACKGROUND: Yodelling is a special kind of vocal performance in traditional music which consists of rapid and repeated changes in pitch. It is assumed that these pitch changes are accompanied by register changes. MATERIAL AND METHODS: We analysed, using the laryngograph, yodelling on different vowels by four professional yodelling teachers (two male, two female), four professional classically trained singers, and four untrained voices. RESULTS: Results reveal that pitch changes in yodelling are associated with decrease of electroglottograpgic (EGG) contact quotient for the upper pitch, indicating a register shift. Furthermore, in contrast to untrained voices, for the yodellers lower and upper pitches were more stable with respect to fundamental frequency and perturbation values, and the pitch transitions were faster. PMID- 20350069 TI - Self-rated health and employment status in patients with multiple sclerosis. AB - PURPOSE: The aim is to explore the association between self-rated health and employment status in patients with multiple sclerosis (MS) when controlling for age, gender, functional disability, disease duration, anxiety and depression. METHOD: One hundred eighty-four people with MS completed a sociodemographic questionnaire that included questions on employment status, the first item of the Short Form-36 Health Survey and the Hospital Anxiety and Depression Scale. Functional disability was assessed using the Expanded Disability Status Scale. The probability of good self-rated health in employed persons was investigated using stepwise logistic regression analyses. RESULTS: Patients with MS who reported good self-rated health were 2.46 times more likely to be employed (95% confidence interval [CI]: 1.08-5.59). Patients without anxiety were 2.64 times more likely to be employed (95%CI: 1.23-5.67). Patients with higher EDSS scores were 0.49 times less likely to be employed (95%CI: 0.33-0.70). Age, gender, disease duration and the presence of depression did not show an increased chance of patient employment. CONCLUSIONS: Patients with MS with good self-rated health are more likely to be employed, even after adjusting for age, gender, education, functional disability, disease duration, depression and anxiety. Dependent on the findings of longitudinal studies unravelling the relevant causal pahways, self rated health might be used as a quick and cheap prognostic marker, which could warn about the possible loss of employment, or changes in functional disability. PMID- 20350071 TI - One-year follow-up study of self-evaluated effects of voice massage, voice training, and voice hygiene lecture in female teachers. AB - This study collected data on self-reported symptoms of vocal fatigue among Finnish female primary school teachers (n = 90) before and 6 months and 12 months after three types of interventions that aimed at improving vocal well-being at work. All subjects were given a voice hygiene lecture (3 hours), and, additionally, a randomly chosen group of 30 subjects was given voice massage treatment and another group voice training (5 x 1 hour sessions) over 2 months. The subjects answered a questionnaire over the Internet concerning symptoms of vocal fatigue. The sum score of symptoms decreased significantly in all three groups through the period of investigation. All three interventions improved the teachers' vocal well-being over the long term. PMID- 20350072 TI - Developing a 3D model of the laryngeal cartilages using HRCT data and MIMICS's segmentation software. AB - Discussions relating to the biomechanics of the larynx are still generally controversial. The purpose of this study is to develop a 3D model of the larynx based on high-resolution computer tomography (HRCT) data identifying and visualizing anatomical landmarks and structures of the larynx. We examined four fresh cadaver larynges with HRCT. The DICOM (Digital Imaging and Communication in Medicine) data were post-processed with the software package MIMICS for three dimensional visualization. All relevant structures of the laryngeal cartilages could be identified on HRCT and visualized in a 3D model. We conclude that 1) HRCT provides excellent data for three-dimensional visualization of the laryngeal anatomy, and 2) the combined technology of HRCT and MIMICS is useful to study the biomechanics on 3D images and for preoperative planning of laryngeal framework surgery. PMID- 20350073 TI - Mistuning in two-part singing. AB - This research describes the strategy of singers in reacting to the pitch deviation from equally tempered (ET) value in their ensemble partner's part in singing two-part a cappella music, and the ability of professional musicians to identify such deviations. Professional singers preferred to maintain the purity of melodic intervals in their own part and to ignore the occurring harmonic mistuning with their deviating ensemble partner. In multi-part singing, the musical interval perception ability of the singers is more finely honed for production than it is for perception, which can be explained by the enhancing effect of the memory of how to vocally produce the intervals, available only in the process of singing. PMID- 20350074 TI - The relationship between subjective self-rating and objective voice assessment measures. AB - INTRODUCTION: Comprehensive protocols of voice disorders have to consist of both subjective and objective tools to study vocal performance. Comparing subjective to objective measures is essential to determine their usefulness in assessing dysphonia. AIM: The aim of the study is to study the correlation of objective voice measures and the patient's subjective self-rating assessment. SUBJECTS AND METHODOLOGY: A total of 100 patients with voice complaints due to various pathological disorders were subjected to voice assessment protocol using: auditory perceptual assessment, acoustic voice assessment, aerodynamic measures, and Voice Problem Self-Assessment Scale (VPSS). RESULTS: The results revealed a variable correlation between functional and emotional clusters of VPSS and overall grade of dysphonia. A moderate correlation between Dysphonia Severity Index (DSI) and VPSS total and emotional cluster was found. Acoustic parameters such as Shim (Shimmer Percent), APQ (Amplitude Perturbation Quotient), and NHR (Noise to Harmonic Ratio), in addition to MPT (Maximum Phonation Time), contributed to total VPSS and emotional cluster scores. The subglottic pressure was the only predictor variable for phonasthenic cluster scores. CONCLUSION: This cross-sectional study highlights that patients' self-perception of a voice problem is related to their difficulty in sustaining controlled loudness and adequate glottic closure rather than in controlling frequency irregularity. PMID- 20350075 TI - A single-centre retrospective review of unilateral and bilateral Dysport injections in adductor spasmodic dysphonia. AB - We reviewed the results and side-effect profile of the Dysport preparation of botulinum toxin A (BTA) in the management of the adductor spasmodic dysphonia. We performed 272 injection episodes in 68 patients, 42 (62%) female, 26 (38%) male. A total of 116 of these injections were unilateral, and 156 were bilateral; 94% of the injections were considered to have been successful with a voice score of 2 or higher. The mean duration of effect (injection intervals) was 128.8 days in the unilateral cohort and 118.7 days in the bilateral (P > 0.05). We injected a relatively lower dose of BTA for unilateral injection episodes in our institution compared to those reported by others to produce comparable results and side effect profiles. PMID- 20350076 TI - Experimental flow study of modeled regular and irregular glottal closure types. AB - The present study shows the results of visualization experiments of the jet formation through a dynamic model of the human vocal folds. The model consists of two counter-rotating, 3D-shaped driven cams covered with a stretched silicone membrane. The 3D contours of the cams are a result of an optimized mapping of observed characteristic clinical vocal fold motions. The experiments are performed by using cams which produce the convex, triangular, rectangular, and concave or sand-glass regular glottis closure types. Two irregular cases are investigated: one of the convex cams is statically closed or opened. These cases cause an oscillating jet which attaches to the ventricular folds and appears to change the part of the aero-acoustic sound spectrum induced by vortices. PMID- 20350077 TI - Voice characteristics of amateur female tenors are comparable with those of male tenors. AB - In order to explore the suitability of adding female voices to the tenor sections of amateur choirs, six male and six female tenors were screened for voice characteristics. Audio signals and signals from an electroglottograph were analyzed by means of VoceVista computer software. All subjects produced closed quotients of 60% or higher in singing with a loud chest voice. There was more variance between the individuals than between groups of male and female singers. Long-time average spectra showed a general trend in the presence of a high intensity peak between 4 and 5 kHz. The results revealed no significant differences in the most important voice characteristics between female and male tenor voices. PMID- 20350122 TI - The association between cognitive factors, pain and disability in patients with idiopathic chronic neck pain. AB - PURPOSE: The aim of this study was to establish the relationship between known cognitive factors and levels of pain and disability in patients with idiopathic chronic neck pain. METHOD: Ninety-four patients referred for physiotherapy because of chronic neck pain completed measures of pain, disability, catastrophising, pain-related fear, pain vigilance and awareness and self efficacy beliefs. Hierarchical multiple regression analyses were then performed to establish whether the cognitive factors were significant determinants of levels of pain and disability. RESULTS: The cognitive measures were significantly related to levels of pain and disability, explaining 23% of the variance in pain intensity and 30% of the variance in disability. Specifically, greater catastrophising (beta = 0.37, p < 0.05) and lower pain vigilance and awareness (beta = - 0.32, p < 0.05) were associated with greater pain intensity. Moreover, greater catastrophising (beta = 0.26, p < 0.05) and lower functional self-efficacy beliefs (beta = - 0.34, p < 0.001) were significantly associated with greater levels of disability. CONCLUSIONS: Cognitive factors were strongly related to levels of pain and disability in patients with chronic neck pain. In view of this, targeting the modification of these cognitive factors should be an integral part of therapy when treating patients with idiopathic chronic neck pain. PMID- 20350123 TI - Pharmacogenomics: the importance of accurate phenotypes. AB - Lack of knowledge regarding genotype-phenotype correlations is often cited as the major barrier delaying the uptake of pharmacogenomics into routine medical practice. When we look forward to genome-wide association studies as one of the most promising tools for overcoming the pharmacogenomics knowledge barrier, we must keep in mind that having large patient cohorts may not help improve our understanding of alleles implicated in drug-response phenotypes, unless we ensure that such phenotypes are precise and pertinent. It may be wiser, and far more cost effective, to invest scarce research funding in accurate patient drug response phenotyping than to genotype (or fully sequence) hundreds to thousands of study participants. Biobanks created with personalized medicine research in mind should, when possible, have access to donors' clinical data, including detailed disease- and drug-response phenotypes. PMID- 20350125 TI - Pharmacogenomics of membrane transporters: past, present and future. AB - Membrane transporters are major determinants of the absorption, distribution and elimination of many of the most commonly used drugs. In the past decade, the field of membrane transporter pharmacogenomics has undergone enormous growth. In particular, functional genomic and clinical studies have provided new information regarding the contribution of coding variants in transporters to drug disposition and response. With continuing advances in sequencing technologies and large-scale human variation studies, over the next decade, knowledge in the field will be transformed. In particular, functional variants in noncoding regions of transporters will be discovered, and large clinical studies will result in the identification of variants in multiple genes, including transporter genes, which contribute to variation in clinical drug response. PMID- 20350124 TI - Approaches to the discovery of pharmacogenomic markers in oncology: 2000-2010 2020. AB - Pharmacogenomics is emerging as an important component both in facilitating new drug development and in improving the utility of existing chemotherapeutic agents. Both candidate gene and genome-wide approaches have been used to identify genetic markers associated with chemotherapeutic response and/or toxicity. New molecular targeted agents have been designed based on a sophisticated understanding of the molecular alterations defining cancers. Over the next decade, the translation of these findings into clinical practice, as well as functional studies of genetic variants, is likely to take center stage. More comprehensive evaluation of the human genome, including the examination of rare SNPs, copy number variations, tandem repeats and epigenetic effects, will further improve our understanding of the relationship between genetics and drug response. PMID- 20350126 TI - Advances in pharmacogenomics technologies. AB - The past decade has seen major advances in our understanding of genomics, with the development of newer and refined technologies. Improvements in the sensitivity and precision of DNA microarrays coupled with the emergence of massively parallel sequencing techniques have redefined how we interrogate the human genome. These tools have facilitated rapid biomarker discovery, uncovered novel targets for therapeutic intervention and enabled mechanistic studies that have helped unravel the mode of drug action. The assessment of drug toxicity based on genomic signatures associated with disease and high-throughput screening for polymorphic interindividual variability in drug responses are procedures that have greatly aided the quality of patient care. The integration of pharmacogenetic approaches for therapeutic monitoring, and health management approaches for advance clinical treatments, will be based on unique patient phenotype profiles and aimed at minimizing adverse drug reactions. In this brief commentary, the evolution and development of key genomics technologies over the past decade is reviewed. PMID- 20350127 TI - Pharmacogenomics of antihypertensive drugs: past, present and future. AB - Hypertension pharmacogenomics holds the promise of leading to individualized drug treatment approaches for the approximately 1 billion individuals worldwide with hypertension. Prior to 2000, the literature on hypertension pharmacogenomics was quite limited. The last decade has seen a substantial growth in the literature, with several examples of genes that appear to play an important role in antihypertensive response. The last decade has also made apparent the numerous challenges in hypertension pharmacogenomics, and addressing those challenges will be important. Moving forward, it seems clear that collaboration among researchers to allow replication or joint analyses will be essential in advancing the field, as will the use of genome-wide association approaches. The next decade should clearly define the clinical potential for hypertension pharmacogenomics. PMID- 20350128 TI - Pharmacogenetics of coumarinic oral anticoagulants. AB - Coumarinic oral anticoagulants are life-saving drugs, but are also one of the leading causes of drug-induced major bleeding events. Moreover, there is substantial individual variation in response to coumarinic oral anticoagulants caused by several factors including variations in the CYP2C9 and VKORC1 genes. Several retrospective and a few small prospective clinical studies have shown that polymorphisms in CYP2C9 and VKORC1 genes together account for 35-50% of the variability in warfarin initiation and maintenance dose requirements. Large randomized clinical trials are currently underway to further solidify the safety, clinical utility and cost-effectiveness of pharmacogenetic-guided dosing algorithms for warfarin, acenocoumarol and phenprocoumon. By 2020, coumarinic oral anticoagulant pharmacogenetic testing will be part of routine clinical practice in anticoagulant therapy. PMID- 20350129 TI - Drug-induced hypersensitivity reactions and pharmacogenomics: past, present and future. AB - Drug-induced hypersensitivity reactions represent a major concern for clinicians, patients, regulators and drug developers. Severe hypersensitivity is associated with high morbidity and mortality, it cannot be predicted from the known pharmacology of the drug and it is usually detected post-marketing when a large number of patients have been exposed to a particular drug. Recent success in developing clinically useful genetic tests that have allowed us to predict the risk of abacavir-induced hypersensitivity has helped to pave the path for a pharmacogenetic approach. However, the loop from identifying a genetic association to improving clinical outcome is still lacking for many drugs. In this commentary, we discuss the progress of hypersensitivity pharmacogenomics over the last decade and point out what remains to be done in the future. The current efforts of the international community are focused on the development of consortia, which aim to standardize disease phenotypes, but also to collect larger numbers of well-phenotyped patients and to pool biological samples through these collaborations. In addition, it is necessary to advance our knowledge of hypersensitivity mechanisms through functional studies, which will lead to the development of predictive and diagnostic tests. PMID- 20350130 TI - Pharmacogenomics and bioinformatics: PharmGKB. AB - The NIH initiated the PharmGKB in April 2000. The primary mission was to create a repository of primary data, tools to track associations between genes and drugs, and to catalog the location and frequency of genetic variations known to impact drug response. Over the past 10 years, new technologies have shifted research from candidate gene pharmacogenetics to phenotype-based pharmacogenomics with a consequent explosion of data. PharmGKB has refocused on curating knowledge rather than housing primary genotype and phenotype data, and now, captures more complex relationships between genes, variants, drugs, diseases and pathways. Going forward, the challenges are to provide the tools and knowledge to plan and interpret genome-wide pharmacogenomics studies, predict gene-drug relationships based on shared mechanisms and support data-sharing consortia investigating clinical applications of pharmacogenomics. PMID- 20350131 TI - DNA, drugs and chariots: on a decade of pharmacogenomics at the US FDA. AB - Over the past 10 years, the US FDA has become a strong pharmacogenomics advocate as part of its mission to both protect and advance public health by enabling innovations that make medicines safer to use and more effective. The agency has evolved its advocacy cautiously on a foundation of science-based information from novel programs, such as the Voluntary Genomics Data Submission initiative, and on careful regulatory assessment of the extraordinary advances in clinical pharmacogenomics that have supported the update of drug labels with genetic information. This commentary goes into detail on the evolution of these achievements. However, many challenges remain for pharmacogenomics, and they will continue to evolve, and all stakeholders must work together. As the decade draws to a close, we have presented four major areas that need to be addressed collectively to assure that pharmacogenomics continues to mature over the next 10 years into a science that is essential to the practice of medicine. PMID- 20350132 TI - Teaching computers to read the pharmacogenomics literature ... so you don't have to. PMID- 20350135 TI - Prospective association of dopamine-related polymorphisms with smoking cessation in general care. AB - AIMS: Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial. MATERIALS & METHODS: We examined genotypes at two dopamine related loci, DRD2/ANKK1 (rs1800497) and DBH (rs77905), in 577 heavy smokers participating in a prospective study of smoking cessation in general care in Germany. RESULTS: Smoking status after 1 year was significantly associated with DRD2/ANKK1, odds of abstinence being 4.4-fold (95% CI: 1.5-12.9) increased in TT- versus CC-homozygous subjects (p = 0.008). No effect was observed for the DBH genotype. The smoking cessation drug bupropion appeared to be particularly effective in CC-homozygotes (among CC subjects there was a 28% higher cessation probability among those taking buproprion; among T carrier subjects there was an increase only by 12%). CONCLUSION: The large effects observed for DRD2/ANKK1 might be related to our study design, in which individual therapy was decided by the physician. Further studies are needed to clarify the genetic effects of DRD2/ANKK1 especially in 'real-life' settings outside clinical trials. PMID- 20350136 TI - Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response. AB - AIMS: The antidepressant escitalopram (S-CIT) is metabolized by the cytochrome P450 (CYP) enzymes CYP 2D6, 2C19 and 3A4. This study evaluated the impact of CYP2D6, 2C19 and 3A4 genetic polymorphisms on plasma concentrations of S-CIT and patient treatment response. MATERIALS & METHODS: A total of 100 patients diagnosed with major depressive disorder were recruited to the study and their depression symptoms were assessed using the Hamilton Depression Rating Scale. The genetic polymorphisms *4, *5 and *10 on CYP2D6, *2, *3 and *17 on CYP2C19, and *18 on CYP3A4 were selected based on their function and respective allele frequencies in Asian populations. Polymorphisms were analyzed using the SNPstream genotyping system, PCR and direct sequencing methods. The steady-state serum concentrations of S-CIT and its metabolites S-desmethylcitalopram and S didesmethylcitalopram were analyzed by HPLC. According to semiquantitative gene dose (SGD) and gene dose (GD) models for allele combinations of these polymorphisms, CYP2D6 was clustered into intermediate (0.5, 1 and 1.5 SGD) and extensive (2 SGD) metabolizers, while CYP2C19 was clustered into poor (0 GD) and extensive (1 and 2 GDs) metabolizers. RESULTS: The group of patients with intermediate CYP2D6 metabolism (0.5 SGD) had a significantly higher frequency of remitters from major depressive disorder during the 8-week treatment (p = 0.0001). Furthermore, CYP2C19 poor metabolizers had significantly higher S-CIT serum levels than did extensive metabolizers at weeks 2, 4 and 8 (p < 0.05). The allele frequencies in CYP3A4*18 and CYP2C19*17 were too low to permit further subgroup analyses. CONCLUSION: Our results suggest that the genetic polymorphisms in CYP2C19 may be influencing S-CIT serum concentrations, and that specific CYP2D6 polymorphisms may be predicting patient treatment outcomes based on gene dosage analyses. PMID- 20350137 TI - Functional analysis of the role of the TPMT gene promoter VNTR polymorphism in TPMT gene transcription. AB - AIMS: Thiopurine S-methyltransferase (TPMT) activity is polymorphic, and a trimodal distribution has been demonstrated in Caucasians (low, intermediate and high methylator groups). The TPMT gene promoter contains a variable number of three GC-rich tandem repeats, namely A, B and C, ranging from three to nine in length in a A(n)B(m)C architecture. MATERIALS & METHODS: Here, we investigated the influence of number and type of TPMT gene promoter tandem repeats on human TPMT gene transcription in K562 cells transiently transfected with reporter constructs bearing various variable number of tandem repeats (VNTR) and addressed the interaction of transcription factor binding to the VNTRs by electrophoretic mobility shift assays. RESULTS: We found that the distribution patterns of VNTR alleles do not significantly differ among acute lymphoblastic leukemia patients, acute myeloid leukemia patients and normal individuals. We also demonstrated that the A repeat has a negative effect in TPMT gene transcription and that a positive regulatory element, identified immediately upstream to the VNTR region of the TPMT gene promoter, is indispensable for TPMT gene transcription. Our electrophoretic mobility shift assay analysis indicated that the Sp1 and Sp3 transcription factors bind to the VNTR repeats. CONCLUSION: Overall, our data underline that both the number and type of VNTRs, as well as the upstream regulatory region of the TPMT gene promoter, determine the overall level of TPMT gene transcription. It remains to be seen whether these VNTRs can be employed as pharmacogenetic markers to individualize thiopurine therapy. PMID- 20350138 TI - Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry. AB - BACKGROUND: Pharmacogenetics is the study of genetic variations that cause alterations in drug level, drug response and adverse drug reactions. SNPs found in CYP450 genes have the greatest genetic influences on interindividual variability in drug bioavailability. The polymorphic nature of these genes may modulate several enzyme levels that affect individual responses to pharmacological treatment. Among them, CYP3A4, CYP3A5, CYP2C9 and CYP2C19 isoforms of CYP450 enzymes are involved in the metabolism of many commonly prescribed drugs. AIMS: In this study, we would like to develop a CYP450 genotyping platform that could lead a complete definition of a patient's metabolic genotype in order to improve the clinical outcome of some drug treatments. MATERIALS & METHODS: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Sequenom) to develop a SNP genotyping method. RESULTS: This MALDI-TOF-based multiplexing system allows the simultaneous and efficient genotyping of a set of CYP450 gene polymorphisms. CONCLUSION: The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes. PMID- 20350140 TI - Dyslipidemia in HIV-infected individuals: from pharmacogenetics to pharmacogenomics. AB - HIV-infected individuals may have accelerated atherogenesis and an increased risk for premature coronary artery disease. Dyslipidemia represents a key pro atherogenic mechanism. In HIV-infected patients, dyslipidemia is typically attributed to the adverse effects of antiretroviral therapy. Nine recent genome wide association studies have afforded a comprehensive, unbiased inventory of common SNPs at 36 genetic loci that are reproducibly associated with dyslipidemia in the general population. Genome-wide association study-validated SNPs have now been demonstrated to contribute to dyslipidemia in the setting of HIV infection and antiretroviral therapy. In a Swiss HIV-infected study population, a similar proportion of serum lipid variability was explained by antiretroviral therapy and by genetic background. In the individual patient, both antiretroviral therapy and the cumulative effect of SNPs contribute to the risk of high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol and hypertriglyceridemia. Genetic variants presumably contribute to additional major metabolic complications in HIV-infected individuals, including diabetes mellitus and coronary artery disease. In an effort to explain an increasing proportion of the heritability of complex metabolic traits, ongoing large-scale gene resequencing studies are focusing on the effects of rare SNPs and structural genetic variants. PMID- 20350142 TI - Hovering energetics and thermal balance in Anna's hummingbirds (Calypte anna). AB - We studied the energetics of hover-feeding Anna's hummingbirds, using three different simultaneous techniques: heat loss as estimated via thermal imaging, metabolic rate as measured at a feeder mask using flow-through respirometry, and aerodynamic power estimated from wingbeat kinematic data. These three methods yielded comparable estimates of power output at ambient air temperatures ranging from 18 degrees to 26 degrees C, whereas heat imbalance at higher air temperatures (up to 34 degrees C) suggested loss by mechanisms other than convection and radiation from the body, such as evaporative cooling and enthalpy rise associated with exhaled air and excreted water and convective heat loss from the patagia. Hummingbirds increased wingbeat frequency and decreased stroke amplitude as air temperature increased, but overall muscle efficiency was found to be approximately constant over the experimental range of air temperatures. PMID- 20350139 TI - Use of transcriptomics in understanding mechanisms of drug-induced toxicity. AB - Adverse drug reactions (ADRs) are an important clinical issue and a serious public health risk. Understanding the underlying mechanisms is critical for clinical diagnosis and management of different ADRs. Toxicogenomics can reveal impacts on biological pathways and processes that had not previously been considered to be involved in a drug response. Mechanistic hypotheses can be generated that can then be experimentally tested using the full arsenal of pharmacology, toxicology, molecular biology and genetics. Recent transcriptomic studies on drug-induced toxicity, which have provided valuable mechanistic insights into various ADRs, have been reviewed with a focus on nephrotoxicity and hepatotoxicity. Related issues have been discussed, including extrapolation of mechanistic findings from experimental model systems to humans using blood as a surrogate tissue for organ damage and comparative systems biology approaches. PMID- 20350145 TI - Cost-effectiveness of switching to biphasic insulin aspart from human premix insulin in a US setting. AB - OBJECTIVES: To evaluate the cost-effectiveness of switching to biphasic insulin aspart (BIAsp 30) from human premix insulin for type 2 diabetes patients in the United States (US) setting. METHODS: The previously published and validated IMS Core Diabetes Model was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over 30 years. Patient characteristics and treatment effects were based on Canadian patients included the IMPROVE observational study (n = 311). Mean glycohaemoglobin (HbA(1c)) was 8.4%, duration of diabetes 16 years and prevalence of complications high at baseline. Simulations were conducted from the perspective of a third-party payer, with costs accounted in 2008 US dollars ($). RESULTS: BIAsp 30 was projected to improve life expectancy by 0.202 years and QALE by 0.301 quality-adjusted life-years (QALYs), due to a reduced incidence of most diabetes-related complications. BIAsp 30 was associated with increased lifetime direct medical costs ($76,517 vs. 67,518) and an incremental cost-effectiveness ratio of $29,870 per QALY gained. Long-term outcomes were sensitive to the impact of BIAsp 30 on hypoglycaemia and changes in HbA(1c). CONCLUSIONS: BIAsp 30 may represent a cost-effective treatment option in the US setting for advanced type 2 diabetes patients experiencing poor glycaemic control or hypoglycaemia on human premix insulin. LIMITATIONS: The application of treatment effect data derived from a Canadian cohort to the US setting was a limitation of the cost-effectiveness analysis. The findings of this cost effectiveness analysis are not applicable to insulin-naive diabetes patients. PMID- 20350147 TI - Study of levocetirizine in seasonal allergic rhinitis. AB - OBJECTIVE: To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults. RESEARCH DESIGN AND METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: NCT00621959. MAIN OUTCOME MEASURES: Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs). RESULTS: The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 +/- 0.19; placebo, 9.04 +/- 0.19; adjusted mean difference, -0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified. CONCLUSIONS: In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality. PMID- 20350146 TI - Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension. AB - BACKGROUND: Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension. SCOPE: An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review. FINDINGS: A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years. CONCLUSION: For the first time one study could demonstrate that an improvement in ocular blood flow in the long run results in preservation of visual field in glaucoma patients. Dorzolamide, combined with the beta-blocker timolol, seems to be superior in this regard to brinzolamide plus timolol. PMID- 20350148 TI - Developing good scientific publishing practices: one pharmaceutical company's perspective. AB - BACKGROUND: The scientific publishing practices of the pharmaceutical industry have been heavily criticized in recent years due to the inherent conflict of interest that arises when a pharmaceutical company publishes findings around its own drugs. SCOPE: Eli Lilly and Company ('Lilly') strives for transparency in its day-to-day activities, and, here, shares its principles, policies and practices on publishing "Lilly-sponsored" research. FINDINGS: A conflict of interest does not necessarily equate to biased presentation of research findings, and operating a successful, for-profit business and maintaining a focus on improving the health of patients are not mutually exclusive goals. There is, however, potential for bias, and it is incumbent upon a for-profit to develop publication principles, policies and practices to address this. To this end, Lilly's Principles of Medical Research states that 'Lilly discloses publicly all medical research results that are important to patients, healthcare providers or payers--whether favorable or unfavorable to a Lilly product--in an accurate, objective, and balanced manner ...' The preparation of publications of Lilly-sponsored research involves close collaboration between external (i.e., academic or otherwise non industry employees) and Lilly scientific researchers (including scientific writers), with both serving as authors. Lilly does not support 'ghost' or 'guest' authorship. Authorship is not just recognition of contribution but also public acknowledgement of responsibility for content, and all authors are expected to take an active role in developing the manuscript in line with the International Committee of Medical Journal Editors-based authorship requirements. This is agreed to by authors before the manuscript is started. Lilly provides external authors with access to the trial data for manuscript development. Lilly does not pay external authors for their involvement in manuscript development. Scientific writers at Lilly, often with advanced scientific degrees, offer both scientific and writing expertise in manuscript development and play a project management role. Their role is transparent, and they are included as authors or appropriately acknowledged. CONCLUSION: Lilly has an ongoing commitment to appropriate publishing practices. Sharing company publication principles, policies and practices is one way to demonstrate this commitment and encourage and facilitate open dialogue among all those involved in drug development. PMID- 20350149 TI - Catheter-related polymicrobial bloodstream infections among pediatric bone marrow transplant outpatients--Atlanta, Georgia, 2007. AB - OBJECTIVE: To identify risk factors for polymicrobial bloodstream infections (BSIs) in pediatric bone marrow transplant (BMT) outpatients attending a newly constructed clinic affiliated with a children's hospital. METHODS: All 30 outpatients treated at a new BMT clinic during September 10-21, 2007, were enrolled in a cohort study. The investigation included interviews, medical records review, observations, and bacterial culture and molecular typing of patient and environmental isolates. Data were analyzed using exact conditional logistic regression. RESULTS: Thirteen patients experienced BSIs caused by 16 different, predominantly gram-negative organisms. Presence of a tunneled catheter (odds ratio [OR], 19.9 [95% confidence interval {CI}, 2.4-infinity), catheter access (OR, 13.7 [95% CI, 1.8-infinity]), and flushing of a catheter with predrawn saline (OR, 12.9 [95% CI, 1.0-766.0]) were independently associated with BSI. The odds of experiencing a BSI increased by a factor of 16.8 with each additional injection of predrawn saline (95% CI, 1.8-827.0). Although no environmental source of pathogens was identified, interviews revealed breaches in recommended infection prevention practice and medication handling. Saline flush solutions were predrawn, and multiple doses were obtained from single-dose preservative-free vials to avoid delays in patient care. CONCLUSION: We speculate that infection prevention challenges in the new clinic, combined with successive needle punctures of vials, facilitated extrinsic contamination and transmission of healthcare-associated pathogens. We recommend that preservative-free single use vials not be punctured more than once. Use of single-use prefilled saline syringes might prevent multiuse of single-use saline vials. Storage of saline outside a medication supply system might be advisable. Before opening new clinic facilities, hospitals should consider conducting a mock patient flow exercise to identify infection control challenges. PMID- 20350150 TI - Trends in Clostridium difficile infection among peripartum women. AB - With use of the Nationwide Inpatient Sample, we conducted a study to determine whether rates of Clostridium difficile infection for delivery-associated hospitalizations are increasing. From 1998 to 2006, the number and incidence of C. difficile infection among peripartum women increased significantly. These increases were comparable to those observed in the general hospitalized population. PMID- 20350151 TI - Should national standards for reporting surgical site infections distinguish between primary and revision orthopedic surgeries? AB - OBJECTIVE: To compare the surgical site infection (SSI) rate after primary total hip arthroplasty with the SSI rate after revision total hip arthroplasty. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic in Rochester, Minnesota, a referral orthopedic center. PATIENTS: All patients undergoing primary total hip arthroplasty or revision total hip arthroplasty during the period from January 1, 2002, through December 31, 2006. METHODS: We obtained data on total hip arthroplasties from a prospectively maintained institutional surgical database. We reviewed data on SSIs collected prospectively as part of routine infection control surveillance, using the criteria of the Centers for Disease Control and Prevention for the definition of an SSI. We used logistic regression analyses to evaluate differences between the SSI rate after primary total hip arthroplasty and the SSI rate after revision total hip arthroplasty. RESULTS: A total of 5,696 total hip arthroplasties (with type 1 wound classification) were analyzed, of which 1,381 (24%) were revisions. A total of 61 SSIs occurred, resulting in an overall SSI rate of 1.1% for all total hip arthroplasties. When stratified by the National Nosocomial Infection Surveillance (NNIS) risk index, SSI rates were 0.5%, 1.2%, and 1.6% in risk categories 0, 1, and 2, respectively. After controlling for the NNIS risk index, the risk of SSI after revision total hip arthroplasty was twice as high as that after primary total hip arthroplasty (odds ratio, 2.2 [95% confidence interval, 1.3-3.7]). In the analysis restricted to the development of deep incisional or organ space infections, the risk of SSI after revision total hip arthroplasty was nearly 4 times that after primary total hip arthroplasty (odds ratio, 3.9 [95% confidence interval, 2.0-7.6]). CONCLUSION: Including revision surgeries in the calculation of SSI rates can result in higher infection rates for institutions that perform a larger number of revisions. Taking NNIS risk indices into account does not eliminate this effect. Differences between primary and revision surgeries should be considered in national standards for the reporting of SSIs. PMID- 20350152 TI - Number of teeth as a predictor of cardiovascular mortality in a cohort of 7,674 subjects followed for 12 years. AB - BACKGROUND: That oral health is related to the development of different cardiovascular disorders is reported in a number of studies. This study investigates if different parameters of oral health are associated with future mortality in different cardiovascular disorders in a dose-dependent manner. METHODS: A total of 7,674 subjects (3,300 males and 4,374 females; age range 20 to 89 years) received a dental examination by specialists in periodontology between the years 1976 and 2002. Number of remaining teeth, severity of periodontal disease, number of deepened periodontal pockets, and bleeding on probing were evaluated in relation to cause of death. RESULTS: During a median follow-up period of 12 years, 629 of the subjects died. For 299 subjects the cause of mortality was cardiovascular disease (CVD); 167 of these subjects died from coronary heart disease (CHD); 83 died from stroke; and 49 died from aortic aneurysm or congestive heart failure. The causes of death for the remaining 330 subjects were other than CVD. After adjustment for age, gender, and smoking, number of remaining teeth predicted in a dose-dependent manner all-cause mortality and mortality in CVD and in CHD (P <0.0001 for all), but not mortality from stroke (P = 0.15). Cox regression analysis revealed a seven-fold increased risk for mortality from CHD in subjects with <10 teeth compared to those with >25 teeth. Severity of periodontal disease, number of deepened periodontal pockets, and bleeding on probing were not related to mortality in a dose-dependent manner after adjustment for confounders. CONCLUSION: This fairly large, prospective study with a long follow-up period presents for the first time a dose-dependent relationship between number of teeth and both all-cause and CVD mortality, indicating a link between oral health and CVD, and that the number of teeth is a proper indicator for oral health in this respect. PMID- 20350153 TI - Full-mouth antimicrobial photodynamic therapy in Fusobacterium nucleatum-infected periodontitis patients. AB - BACKGROUND: The purpose of this study is to clinically and microbiologically evaluate the effect of photodynamic therapy (PDT) as a full-mouth procedure in Fusobacterium nucleatum-infected patients with periodontitis. METHODS: In the present study, PDT is administered adjuvantly after scaling and root planing (SRP) to patients with localized chronic periodontitis (LCP). Twenty-four patients, in whom only F. nucleatum was detected by baseline polymerase chain reaction (PCR) after SRP, were randomly assigned to PDT and control groups. PDT was carried out once as a full-mouth disinfection in the test group. The control group was treated with the photosensitizer solution, but without laser irradiation. In all subjects, the clinical parameters plaque index, reddening, bleeding on probing (BOP), probing depth (PD), gingival recession, and clinical attachment level (CAL) were determined at the baseline examination and at 1, 4, and 12 weeks after PDT. Quantitative analysis of the F. nucleatum DNA concentration was performed by competitive PCR. All clinical indices were calculated for each test and control subject as were the median and interquartile range of each group. RESULTS: In patients with LCP who received PDT treatment, significant reductions in reddening, BOP, and mean PD and CAL were observed during the observation period and with respect to controls. Four and 12 weeks after PDT, the mean PD and CAL showed significant differences from baseline values and from those of the control group. In the PDT group, 12 weeks after treatment, the F. nucleatum DNA concentration was found to be significantly reduced compared to the baseline level. CONCLUSION: The results of this study show that the adjuvant application of the described PDT method is appropriate to reduce periodontal inflammatory symptoms and to successfully treat infection with F. nucleatum. PMID- 20350154 TI - Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years. AB - BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events. PMID- 20350155 TI - Smokeless tobacco use and periodontal health in a rural male population. AB - BACKGROUND: Despite the reported effects of smokeless tobacco (ST) on the periodontium and high prevalence of ST use in rural populations and in men, studies on this specific topic are limited. The purpose of this cross-sectional investigation is to evaluate the periodontal health status of male ST users from a rural population. METHODS: Adult male residents of two rural Appalachian Ohio counties and daily ST users, with a unilateral mandibular oral ST keratosis lesion, were recruited. Subjects completed a questionnaire and received oral examination. Teeth present, ST keratosis lesion, plaque and gingival index, probing depth (PD), recession depth (RD), and attachment level were recorded. Statistical analysis compared ST-site mandibular teeth (teeth adjacent to the subject's unilateral ST keratosis lesion) to NST-site teeth (contralateral corresponding teeth). RESULTS: This study includes 73 ST users. Recession prevalence is much greater in ST-site quadrants (36%) compared to NST-site quadrants (18%; P <0.001). Twice as many teeth had recession on ST-site (approximately 20%) than NST-site (approximately 10%; P = 0.0001). Average buccal RD on ST-site teeth did not differ from that on the NST-site teeth (P = 0.0875). Although average buccal attachment loss is greater on ST-site teeth (P = 0.016), the mean difference is <0.5 mm. When stratified by years of ST use, subjects using ST for 10 to 18 years exhibit the most differences between ST and NST sites, whereas subjects using ST for <10 years show no differences. CONCLUSION: The results indicate that greater gingival recession prevalence and extent are associated with ST placement site in rural male ST users. PMID- 20350156 TI - Biofilm formation enhances the oxygen tolerance and invasiveness of Fusobacterium nucleatum in an oral mucosa culture model. AB - BACKGROUND: The present study evaluates the survival capability of Fusobacterium nucleatum strains in an aerobic environment and compares the invasive capability of F. nucleatum in biofilm and planktonic forms in an organotypic cell culture (OCC) model. METHODS: Biofilms of F. nucleatum American Type Culture Collection (ATCC) 25586 or Anaerobe Helsinki Negative (AHN) 9508 were produced by culturing on semipermeable membranes on brucella agar plates. The oxygen tolerance of the F. nucleatum strains was examined by incubating 3-day-old anaerobically grown biofilms in an aerobic environment (CO(2) [5% in air] incubator) for an additional 48 hours. The OCC model was constructed by seeding keratinocytes on a fibroblast-containing collagen gel. In invasion assays, a 3-day-old anaerobically grown biofilm (and planktonic bacteria in solution as the control) was placed upside down on the top of OCC and incubated under 5% CO(2) for 24 hours. Invasion of the bacteria and morphologic changes in OCC were assessed using hematoxylin and eosin, Ki-67, and periodic acid-Schiff stainings. RESULTS: In biofilms, both F. nucleatum strains continuously increased their cell numbers in an aerobic environment for 48 hours. After incubating the bacterial biofilm in contact with the OCC model, F. nucleatum AHN 9508 was able to pass through the epithelial/basement membrane barrier and invade the collagen matrix. The invasiveness of biofilm F. nucleatum ATCC 25586 was limited to the epithelium. Cytotoxic effects and invasiveness of F. nucleatum on the OCC were much stronger when the bacteria were in biofilms than in the planktonic form. CONCLUSION: Biofilm formation regulates the survival and invasiveness of F. nucleatum in an aerobic environment. PMID- 20350157 TI - Hypertension may affect tooth-supporting alveolar bone quality: a study in rats. AB - BACKGROUND: This study evaluates the ligature-induced bone loss (BL) and quality of tooth-supporting alveolar bone in spontaneously hypertensive rats (SHRs) by histometric, histochemical, and immunohistochemical analyses and assesses the effects of lercanidipine on these parameters. METHODS: Wistar rats and SHRs were assigned to one of the following groups: normotensive rats (n = 15), untreated SHRs (n = 15), and treated SHRs (n = 15). The latter group was treated daily with lercanidipine for 45 days. Two weeks after the beginning of drug administration, the first right mandibular molar received a cotton ligature, whereas the contralateral tooth was left unligated. The following parameters were analyzed in the furcation area of decalcified histologic sections: BL, bone density (BD), number of positive cells for tartrate-resistant acid phosphatase (TRAP+), and expression of receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG). RESULTS: In ligated teeth, no significant differences among groups were found regarding BL, TRAP+ cells, and the ratio of RANKL/OPG+ cells (P >0.05), although the expression of RANKL was decreased in the treated SHR group (P <0.05). Increased BL and decreased BD were observed around unligated teeth of the untreated and treated SHR groups (P <0.05). In the furcation area of the unligated teeth, the untreated SHR group presented a higher number of TRAP+ cells and higher ratio of RANKL/OPG+ cells compared to the other groups. CONCLUSIONS: SHRs present harmful alterations in the quality of tooth-supporting bone, independently of inflammation. In addition, the administration of lercanidipine for 45 days decreased the expression of bone-resorption markers. PMID- 20350158 TI - Esthetic treatment of peripheral giant cell granuloma using a subepithelial connective tissue graft and a split-thickness pouch technique. AB - BACKGROUND: Peripheral giant cell granuloma (PGCG) is a reactive hyperplastic lesion involving the gingiva or alveolar mucosa consisting of proliferating endothelial cells, a rich capillary bed, chronic inflammatory cells, fibroblasts, and giant cells. After complete clinical removal of PGCG recurrence occurs in about 10% of cases, and may result in an esthetic and functional soft tissue defect. This report describes a surgical procedure involving complete removal of a gingival PGCG in the maxillary esthetic zone and immediate tissue restoration achieving complete gingival augmentation. METHODS: A 15-year-old female presented with a red, nodular, asymptomatic lesion, approximately 3.5 mm in diameter, located above the maxillary left lateral incisor. The lesion was excised down to the underlying root resulting in a 6 x 5-mm mucogingival dehiscence defect. Corrective surgery included a subepithelial connective tissue graft peripherally covered by the surrounding gingiva and stabilized by 5/0 resorbable sutures. RESULTS: Healing was uneventful, resulting in healthy and esthetic gingiva. Microscopic examination of the biopsy specimen was consistent with the diagnosis of PGCG. CONCLUSIONS: PGCG may follow an aggressive course, sometimes requiring preemptive surgical intervention. Grafting a subepithelial connective tissue graft peripherally covered by the surrounding gingiva, without raising a gingival flap, successfully eliminated the gingival defect. The free gingival margin of the neighboring teeth and the mucogingival junction remained unchanged. PMID- 20350159 TI - Xenogeneic collagen matrix with coronally advanced flap compared to connective tissue with coronally advanced flap for the treatment of dehiscence-type recession defects. AB - BACKGROUND: For root coverage therapy, the connective tissue graft (CTG) plus coronally advanced flap (CAF) is considered the gold standard therapy against which alternative therapies are generally compared. When evaluating these therapies, in addition to traditional measures of root coverage, subject reported, qualitative measures of esthetics, pain, and overall preferences for alternative procedures should also be considered. This study determines if a xenogeneic collagen matrix (CM) with CAF might be as effective as CTG+CAF in the treatment of recession defects. METHODS: This study was a single-masked, randomized, controlled, split-mouth study of dehiscence-type recession defects in contralateral sites; one defect received CTG+CAF and the other defect received CM+CAF. A total of 25 subjects (8 male, 17 female; mean age: 43.7 +/- 12.2 years) were evaluated at 6 months and 1 year. The primary efficacy endpoint was recession depth at 6 months. Secondary endpoints included traditional periodontal measures, such as width of keratinized tissue and percentage of root coverage. Subject-reported values of pain, discomfort, and esthetic satisfaction were also recorded. RESULTS: At 6 months, recession depth was on average 0.52 mm for test sites and 0.10 mm for control sites. Recession depth change from baseline was statistically significant between test and control, with an average of 2.62 mm gained at test sites and 3.10 mm gained at control sites for a difference of 0.4 mm (P = 0.0062). At 1 year, test percentage of root coverage averaged 88.5%, and controls averaged 99.3% (P = 0.0313). Keratinized tissue width gains were equivalent for both therapies and averaged 1.34 mm for test sites and 1.26 mm for control sites (P = 0.9061). There were no statistically significant differences between subject-reported values for esthetic satisfaction, and subjects' assessments of pain and discomfort were also equivalent. CONCLUSION: When balanced with subject-reported esthetic values and compared to historical root coverage outcomes reported by other investigators, CM+CAF presents a viable alternative to CTG+CAF, without the morbidity of soft tissue graft harvest. PMID- 20350160 TI - Reduced clearance of penile human papillomavirus infection in uncircumcised men. AB - The relationship between circumcision and the acquisition and clearance of human papillomavirus (HPV) infection was examined in a cohort of 357 men followed up at 2-month intervals for an average of 431 days. There were no differences in HPV acquisition by circumcision status. Clearance of HPV infection, including infection with oncogenic types, was slower in the glans/coronal sulcus of the penis of uncircumcised men than circumcised men. The median duration of HPV infection of the glans/coronal sulcus was significantly longer in uncircumcised men (154 days) than circumcised men (91 days) (P=.04). Circumcision may protect against HPV-associated disease by enhancing the resolution of infection. PMID- 20350161 TI - Antiretroviral drug resistance in HIV-1-infected patients with low-level viremia. AB - This study characterized the prevalence and patterns of antiretroviral-drug resistance mutations according to plasma human immunodeficiency virus type 1 (HIV 1) RNA load in a large population of patients with HIV-1 infection who underwent testing for resistance mutations in routine clinical practice. HIV-1 genotypic resistance test results with linked clinical data were obtained from national resistance and clinical databases in the United Kingdom. Among 7861 tests, detection of > or =1 resistance mutation was most frequent at viral loads of 300 10,000 copies/mL and decreased statistically significantly at viral loads of >10,000 copies/mL. Major resistance mutations were commonly detected in the subset of tests that were performed among patients with viral loads of <1000 copies/mL (1001 [12.7%] of 7861 tests). We conclude that HIV-1 genotypic resistance testing is informative for patients with low viral loads. PMID- 20350163 TI - Rapid selection of a transmissible multidrug-resistant influenza A/H3N2 virus in an immunocompromised host. AB - BACKGROUND: The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy. METHODS: Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture. RESULTS: An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed. CONCLUSIONS: An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised. PMID- 20350162 TI - Respiratory virus pneumonia after hematopoietic cell transplantation (HCT): associations between viral load in bronchoalveolar lavage samples, viral RNA detection in serum samples, and clinical outcomes of HCT. AB - BACKGROUND: Few data exist on respiratory virus quantitation in lower respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with respiratory virus-associated pneumonia. METHODS: We retrospectively identified HCT recipients with respiratory syncytial virus (RSV), parainfluenza virus, influenza virus, metapneumovirus (MPV), and coronavirus (CoV) detected in bronchoalveolar lavage (BAL) samples, and we tested stored BAL and/or serum samples by quantitative polymerase chain reaction. RESULTS: In 85 BAL samples from 82 patients, median viral loads were as follows: for RSV (n = 35), 2.6 x 10(6) copies/mL; for parainfluenza virus (n = 35), 4.9 x 10(7) copies/mL; for influenza virus (n = 9), 6.8 x 10(5) copies/mL; for MPV (n = 7), 3.9 x 10(7) copies/mL; and for CoV (n = 4), 1.8 x 10(5) copies/mL. Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum samples from 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A virus/CoV coinfection (influenza A virus and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL samples (p = .05), and viral RNA detection in serum was significantly associated with death (adjusted rate ratio, 1.8; (p = .02). CONCLUSION: Quantitative polymerase chain reaction detects high viral loads in BAL samples from HCT recipients with respiratory virus pneumonia. Viral RNA is also detectable in the serum of patients with RSV, influenza, and MPV pneumonia and may correlate with the severity of disease. PMID- 20350164 TI - Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba. AB - BACKGROUND: As part of an evaluation of strategies to make inactivated poliovirus vaccine (IPV) affordable for developing countries, we conducted a clinical trial of fractional doses of IPV in Cuba. METHODS: We compared the immunogenicity and reactogenicity of fractional-dose IPV (0.1 mL, or 1/5 of a full dose) given intradermally using a needle-free jet injector device compared with full doses given intramuscularly. Subjects were randomized at birth to receive IPV at 6, 10, and 14 weeks. RESULTS: A total of 471 subjects were randomized to the 2 study groups, and 364 subjects fulfilled the study requirements. No significant differences at baseline were detected. Thirty days after completing the 3-dose schedule of IPV, 52.9%, 85.0%, and 69.0% of subjects in the fractional-dose IPV arm seroconverted for poliovirus types 1, 2, and 3, respectively, whereas 89.3%, 95.5%, and 98.9% of subjects in the full-dose IPV arm seroconverted for poliovirus types 1, 2, and 3, respectively (all comparisons, P < .001). The median titers of each poliovirus serotype were significantly lower in the intradermal arm than in the intramuscular arm (P < .001). Only minor local adverse effects and no moderate or serious adverse events were reported. CONCLUSIONS: This large-scale evaluation demonstrates the feasibility of fractional doses of IPV given intradermally as an antigen-sparing strategy but also shows that IPV given to infants at 6, 10, and 14 weeks of age results in suboptimal immunogenicity (especially for the fractional-dose arm). PMID- 20350165 TI - Do local adaptation and the reproductive tactic of Atlantic salmon (Salmo salar L.) affect offspring metabolic capacities? AB - Atlantic salmon (Salmo salar L.) is an iteroparous, anadromous species that exhibits some of the greatest within-population variability in size and age at maturity of all vertebrates. In the conditional reproductive strategy of salmonids, the male reproductive tactic expressed is believed to depend on an individual male's status relative to others in the population and therefore depends on his capacity to attain a physiological threshold, the exact nature of which is unknown. Although the threshold is influenced by local biotic and abiotic conditions, it is likely to be under genetic control. Our study examined whether the early growth, muscle metabolic capacities, routine metabolic rate, and spontaneous swimming of salmon alevins reared in laboratory conditions varied with the population of origin, maternal investment, and the paternal reproductive tactic. Our experimental design allowed us to establish that neither the population of origin nor the paternal reproductive tactic influenced the physiological capacities of alevins. The strong influence of the mother on alevin metabolic capacities suggests that the bioenergetic differences in metabolic capacities, realized metabolic rates, and activity levels that could eventually dictate the reproductive tactic of male offspring may originate in maternal effects. PMID- 20350166 TI - Somatic mitochondrial DNA mutations in mammalian aging. AB - Mitochondrial dysfunction is heavily implicated in the multifactorial aging process. Aging humans have increased levels of somatic mtDNA mutations that tend to undergo clonal expansion to cause mosaic respiratory chain deficiency in various tissues, such as heart, brain, skeletal muscle, and gut. Genetic mouse models have shown that somatic mtDNA mutations and cell type-specific respiratory chain dysfunction can cause a variety of phenotypes associated with aging and age related disease. There is thus strong observational and experimental evidence to implicate somatic mtDNA mutations and mosaic respiratory chain dysfunction in the mammalian aging process. The hypothesis that somatic mtDNA mutations are generated by oxidative damage has not been conclusively proven. Emerging data instead suggest that the inherent error rate of mitochondrial DNA (mtDNA) polymerase gamma (Pol gamma) may be responsible for the majority of somatic mtDNA mutations. The roles for mtDNA damage and replication errors in aging need to be further experimentally addressed. PMID- 20350167 TI - The role of the human prefrontal cortex in social cognition and moral judgment. AB - Results from functional magnetic resonance imaging and lesion studies indicate that the prefrontal cortex (PFC) is essential for successful navigation through a complex social world inundated with intricate norms and moral values. This review examines regions of the PFC that are critical for implicit and explicit social cognitive and moral judgment processing. Considerable overlap between regions active when individuals engage in social cognition or assess moral appropriateness of behaviors is evident, underscoring the similarity between social cognitive and moral judgment processes in general. Findings are interpreted within the framework of structured event complex theory, providing a broad organizing perspective for how activity in PFC neural networks facilitates social cognition and moral judgment. We emphasize the dynamic flexibility in neural circuits involved in both implicit and explicit processing and discuss the likelihood that neural regions thought to uniquely underlie both processes heavily interact in response to different contextual primes. PMID- 20350168 TI - Modality-dependent "what" and "where" preparatory processes in auditory and visual systems. AB - The present study examined the modality specificity and spatio-temporal dynamics of "what" and "where" preparatory processes in anticipation of auditory and visual targets using ERPs and a cue-target paradigm. Participants were presented with an auditory (Experiment 1) or a visual (Experiment 2) cue that signaled them to attend to the identity or location of an upcoming auditory or visual target. In both experiments, participants responded faster to the location compared to the identity conditions. Multivariate spatio-temporal partial least square (ST PLS) analysis of the scalp-recorded data revealed supramodal "where" preparatory processes between 300-600 msec and 600-1200 msec at central and posterior parietal electrode sites in anticipation of both auditory and visual targets. Furthermore, preparation for pitch processing was captured at modality-specific temporal regions between 300 and 700 msec, and preparation for shape processing was detected at occipital electrode sites between 700 and 1150 msec. The spatio temporal patterns noted above were replicated when a visual cue signaled the upcoming response (Experiment 2). Pitch or shape preparation exhibited modality dependent spatio-temporal patterns, whereas preparation for target localization was associated with larger amplitude deflections at multimodal, centro-parietal sites preceding both auditory and visual targets. Using a novel paradigm, the study supports the notion of a division of labor in the auditory and visual pathways following both auditory and visual cues that signal identity or location response preparation to upcoming auditory or visual targets. PMID- 20350170 TI - General-purpose monitoring during speech production. AB - The concept of "monitoring" refers to our ability to control our actions on-line. Monitoring involved in speech production is often described in psycholinguistic models as an inherent part of the language system. We probed the specificity of speech monitoring in two psycholinguistic experiments where electroencephalographic activities were recorded. Our focus was on a component previously reported in nonlinguistic manual tasks and interpreted as a marker of monitoring processes. The error negativity (Ne, or error-related negativity), thought to originate in medial frontal areas, peaks shortly after erroneous responses. A component of seemingly comparable properties has been reported, after errors, in tasks requiring access to linguistic knowledge (e.g., speech production), compatible with a generic error-detection process. However, in contrast to its original name, advanced processing methods later revealed that this component is also present after correct responses in visuomotor tasks. Here, we reported the observation of the same negativity after correct responses across output modalities (manual and vocal responses). This indicates that, in language production too, the Ne reflects on-line response monitoring rather than error detection specifically. Furthermore, the temporal properties of the Ne suggest that this monitoring mechanism is engaged before any auditory feedback. The convergence of our findings with those obtained with nonlinguistic tasks suggests that at least part of the monitoring involved in speech production is subtended by a general-purpose mechanism. PMID- 20350169 TI - Picture superiority doubly dissociates the ERP correlates of recollection and familiarity. AB - Two experiments investigated the processes underlying the picture superiority effect on recognition memory. Studied pictures were associated with higher accuracy than studied words, regardless of whether test stimuli were words (Experiment 1) or pictures (Experiment 2). Event-related brain potentials (ERPs) recorded during test suggested that the 300-500 msec FN400 old/new effect, hypothesized to be related to familiarity-based recognition, benefited from study/test congruity, such that it was larger when study and test format remained constant than when they differed. The 500-800 msec parietal old/new effect, hypothesized to be related to recollection, benefited from studying pictures, regardless of test format. The parallel between the accuracy and parietal ERP results suggests that picture superiority may arise from encoding the distinctive attributes of pictures in a manner that enhances their later recollection. Furthermore, when words were tested, opposite effects of studying words versus studying pictures were observed on the FN400 (word > picture) versus parietal (picture > word) old/new effects--providing strong evidence for a crossover interaction between these components that is consistent with a dual-process perspective. PMID- 20350171 TI - Beyond the memory mechanism: person-selective and nonselective processes in recognition of personally familiar faces. AB - Special processes recruited during the recognition of personally familiar people have been assumed to reflect the rich episodic and semantic information that selectively represents each person. However, the processes may also include person nonselective ones, which may require interpretation in terms beyond the memory mechanism. To examine this possibility, we assessed decrease in differential activation during the second presentation of an identical face (repetition suppression) as an index of person selectivity. During fMRI, pictures of personally familiar, famous, and unfamiliar faces were presented to healthy subjects who performed a familiarity judgment. Each face was presented once in the first half of the experiment and again in the second half. The right inferior temporal and left inferior frontal gyri were activated during the recognition of both types of familiar faces initially, and this activation was suppressed with repetition. Among preferentially activated regions for personally familiar over famous faces, robust suppression in differential activation was exhibited in the bilateral medial and anterior temporal structures, left amygdala, and right posterior STS, all of which are known to process episodic and semantic information. On the other hand, suppression was minimal in the posterior cingulate, medial prefrontal, right inferior frontal, and intraparietal regions, some of which were implicated in social cognition and cognitive control. Thus, the recognition of personally familiar people is characterized not only by person selective representation but also by nonselective processes requiring a research framework beyond the memory mechanism, such as a social adaptive response. PMID- 20350172 TI - Changes in cerebello-motor connectivity during procedural learning by actual execution and observation. AB - The cerebellum is involved in motor learning of new procedures both during actual execution of a motor task and during observational training. These processes are thought to depend on the activity of a neural network that involves the lateral cerebellum and primary motor cortex (M1). In this study, we used a twin-coil TMS technique to investigate whether execution and observation of a visuomotor procedural learning task is related to modulation of cerebello-motor connectivity. We observed that, at rest, a magnetic conditioning pulse applied over the lateral cerebellum reduced the motor-evoked potentials obtained by stimulating the contralateral M1, indicating activation of a cerebello-motor connection. Furthermore, during procedural learning, cerebellar stimulation resulted in selective facilitation, not inhibition, of contralateral M1 excitability. The effects were evident when motor learning was obtained by actual execution of the task or by observation, but they disappeared if procedural learning had already been acquired by previous observational training. These results indicate that changes in cerebello-motor connectivity occur in relation to specific phases of procedural learning, demonstrating a complex pattern of excitatory and inhibitory drives modulated across time. PMID- 20350173 TI - The packet switching brain. AB - The computer metaphor has served brain science well as a tool for comprehending neural systems. Nevertheless, we propose here that this metaphor be replaced or supplemented by a new metaphor, the "Internet metaphor," to reflect dramatic new network theoretic understandings of brain structure and function. We offer a "weak" form and a "strong" form of this metaphor: The former suggests that structures and processes unique to Internet-like architectures (e.g., domains and protocols) can profitably guide our thinking about brains, whereas the latter suggests that one particular feature of the Internet-packet switching-may be instantiated in the structure of certain brain networks, particularly mammalian neocortex. PMID- 20350174 TI - Effects of anterior cingulate microstimulation on pro- and antisaccades in nonhuman primates. AB - Numerous studies have established a role for the ACC in cognitive control. Current theories are at odds as to whether ACC itself directly engages or alternatively recruits other frontal cortical areas that implement control. The antisaccade task, in which subjects are required to make a saccade to the location opposite a suddenly appearing visual stimulus, is a simple oculomotor paradigm that has been used extensively to investigate flexible oculomotor control. Here, we tested a causal role of the dorsal ACC in cognitive control by applying electrical microstimulation during a preparatory period while monkeys performed alternating blocks of pro- and antisaccade trials. Microstimulation induced significant changes in saccadic RTs (SRTs) in both tasks. On prosaccade trials, SRTs were increased for saccades contralateral to and decreased for saccades ipsilateral to the stimulated hemisphere. In contrast, SRTs were decreased for both ipsi- and contralaterally directed antisaccades. These data show that microstimulation administered during response preparation facilitated the performance of antisaccades and are suggestive of a direct role of ACC in the implementation of cognitive control. PMID- 20350175 TI - Contextual priming in grapheme-color synesthetes and yoked controls: 400 msec in the life of a synesthete. AB - Grapheme-color synesthesia is a heritable trait where graphemes ("2") elicit the concurrent perception of specific colors (red). Researchers have questioned whether synesthetic experiences are meaningful or simply arbitrary associations and whether these associations are perceptual or conceptual. To address these fundamental questions, ERPs were recorded as 12 synesthetes read statements such as "The Coca-Cola logo is white and 2," in which the final grapheme induced a color that was either contextually congruous (red) or incongruous ("...white and 7," for a synesthetes who experienced 7 as green). Grapheme congruity was found to modulate the amplitude of the N1, P2, N300, and N400 components in synesthetes, suggesting that synesthesia impacts perceptual as well as conceptual aspects of processing. To evaluate whether observed ERP effects required the experience of colored graphemes versus knowledge of grapheme-color pairings, we ran three separate groups of controls on a similar task. Controls trained to a synesthete's associations elicited N400 modulation, indicating that knowledge of grapheme-color mappings was sufficient to modulate this component. Controls trained to synesthetic associations and given explicit visualization instructions elicited both N300 and N400 modulations. Lastly, untrained controls who viewed physically colored graphemes ("2" printed in red) elicited N1 and N400 modulations. The N1 grapheme congruity effect began earlier in synesthetes than colored grapheme controls but had similar scalp topography. Data suggest that, in synesthetes, achromatic graphemes engage similar visual processing networks as colored graphemes in nonsynesthetes and are in keeping with models of synesthesia that posit early feed-forward connections between form and color processing areas in extrastriate cortex. The P2 modulation was unique to the synesthetes and may reflect neural activity that underlies the conscious experience of the synesthetic induction. PMID- 20350176 TI - Level of processing modulates the neural correlates of emotional memory formation. AB - Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information. PMID- 20350177 TI - Viewing one's own face being touched modulates tactile perception: an fMRI study. AB - The perception of tactile stimuli on the face is modulated if subjects concurrently observe a face being touched; this effect, termed visual remapping of touch (VRT), is maximum for observing one's own face. In the present fMRI study, we investigated the neural basis of the VRT effect. Participants in the scanner received tactile stimuli, near the perceptual threshold, on their right, left, or both cheeks. Concurrently, they watched movies depicting their own face, another person's face, or a ball that could be touched or only approached by human fingers. Participants were requested to distinguish between unilateral and bilateral tactile stimulation. Behaviorally, perception of tactile stimuli was modulated by viewing a tactile stimulation, with a stronger effect when viewing one's own face being touched. In terms of brain activity, viewing touch was related with an enhanced activity in the ventral intraparietal area. The specific effect of viewing touch on oneself was instead related with a reduced activity in both the ventral premotor cortex and the somatosensory cortex. The present findings suggest that VRT is supported by a network of fronto-parietal areas. The ventral intraparietal area might remap visual information about touch onto tactile processing. Ventral premotor cortex might specifically modulate multisensory interaction when sensory information is related to one's own body. Then this activity might back project to the somatosensory cortices, thus affecting tactile perception. PMID- 20350178 TI - How different types of conceptual relations modulate brain activation during semantic priming. AB - Semantic priming, a well-established technique to study conceptual representation, has thus far produced variable fMRI results, both regarding the type of priming effects and their correlation with brain activation. The aims of the current study were (a) to investigate two types of semantic relations- categorical versus associative--under controlled processing conditions and (b) to investigate whether categorical and associative relations between words are correlated with response enhancement or response suppression. We used fMRI to examine neural correlates of semantic priming as subjects performed a lexical decision task with a long SOA (800 msec). Four experimental conditions were compared: categorically related trials (couch-bed), associatively related trials (couch-pillow), unrelated trials (couch-bridge), and nonword trials (couch sibor). We found similar behavioral priming effects for both categorically and associatively related pairs. However, the neural priming effects differed: Categorically related pairs resulted in a neural suppression effect in the right MFG, whereas associatively related pairs resulted in response enhancement in the left IFG. A direct contrast between them revealed activation for categorically related trials in the right insular lobe. We conclude that perceptual and functional similarity of categorically related words may lead to response suppression within right-lateralized frontal regions that represent more retrieval effort and the recruitment of a broader semantic field. Associatively related pairs that require a different processing of the related target compared to the prime may lead to the response enhancement within left inferior frontal regions. Nevertheless, the differences between associative and categorical relations might be parametrical rather than absolutely distinct as both relationships recruit similar regions to a different degree. PMID- 20350179 TI - What does the right hemisphere know about phoneme categories? AB - Innate auditory sensitivities and familiarity with the sounds of language give rise to clear influences of phonemic categories on adult perception of speech. With few exceptions, current models endorse highly left-hemisphere-lateralized mechanisms responsible for the influence of phonemic category on speech perception, based primarily on results from functional imaging and brain-lesion studies. Here we directly test the hypothesis that the right hemisphere does not engage in phonemic analysis. By using fMRI to identify cortical sites sensitive to phonemes in both word and pronounceable nonword contexts, we find evidence that right-hemisphere phonemic sensitivity is limited to a lexical context. We extend the interpretation of these fMRI results through the study of an individual with a left-hemisphere lesion who is right-hemisphere reliant for initial acoustic and phonetic analysis of speech. This individual's performance revealed that the right hemisphere alone was insufficient to allow for typical phonemic category effects but did support the processing of gradient phonetic information in lexical contexts. Taken together, these findings confirm previous claims that the right temporal cortex does not play a primary role in phoneme processing, but they also indicate that lexical context may modulate the involvement of a right hemisphere largely tuned for less abstract dimensions of the speech signal. PMID- 20350180 TI - Multimodal imaging of incidental retrieval: the low route to memory. AB - Memories of past episodes frequently come to mind incidentally, without directed search. It has remained unclear how incidental retrieval processes are initiated in the brain. Here we used fMRI and ERP recordings to find brain activity that specifically correlates with incidental retrieval, as compared to intentional retrieval. Intentional retrieval was associated with increased activation in dorsolateral prefrontal cortex. By contrast, incidental retrieval was associated with a reduced fMRI signal in posterior brain regions, including extrastriate and parahippocampal cortex, and a modulation of a posterior ERP component 170 msec after the onset of visual retrieval cues. Successful retrieval under both intentional and incidental conditions was associated with increased activation in the hippocampus, precuneus, and ventrolateral prefrontal cortex, as well as increased amplitude of the P600 ERP component. These results demonstrate how early bottom-up signals from posterior cortex can lead to reactivation of episodic memories in the absence of strategic retrieval attempts. PMID- 20350181 TI - The neural substrates of recognition memory for verbal information: spanning the divide between short- and long-term memory. AB - One of the classic categorical divisions in the history of memory research is that between short-term and long-term memory. Indeed, because memory for the immediate past (a few seconds) and memory for the relatively more remote past (several seconds and beyond) are assumed to rely on distinct neural systems, more often than not, memory research has focused either on short- (or "working memory") or on long-term memory. Using an auditory-verbal continuous recognition paradigm designed for fMRI, we examined how the neural signatures of recognition memory change across an interval of time (from 2.5 to 30 sec) that spans this hypothetical division between short- and long-term memory. The results revealed that activity during successful auditory-verbal item recognition in inferior parietal cortex and the posterior superior temporal lobe was maximal for early lags, whereas, conversely, activity in the left inferior frontal gyrus increased as a function of lag. Taken together, the results reveal that as the interval between item repetitions increases, there is a shift in the distribution of memory-related activity that moves from posterior temporo-parietal cortex (lags 1 4) to inferior frontal regions (lags 5-10), indicating that as time advances, the burden of recognition memory is increasingly placed on top-down retrieval mechanisms that are mediated by structures in inferior frontal cortex. PMID- 20350183 TI - Task context and frontal lobe activation in the Stroop task. AB - The ability to step outside a routine--to select a new response over a habitual one--is a cardinal function of the frontal lobes. A large body of neuroimaging work now exists pointing to increased activation within the anterior cingulate when stimuli evoke competing responses (incongruent trials) relative to when responses converge (congruent trials). However, lesion evidence that the ACC is necessary in this situation is inconsistent. We hypothesized that this may be a consequence of different task procedures (context) used in lesion and neuroimaging studies. The present study attempted to reconcile the lesion and the fMRI findings by having subjects perform clinical and experimental versions of the Stroop task during BOLD fMRI acquisition. We examined the relationship of brain activation patterns, specifically within the anterior cingulate and left dorsolateral frontal regions, to congruent and incongruent trial types in different task presentations or contexts. The results confirmed our hypothesis that ACC activity is relatively specific to unblocked-uncued incongruent Stroop conditions that have not been used in large neuropsychological studies. Moreover, the size of the behavioral Stroop interference effect was significantly correlated with activity in ACC and left dorsolateral regions, although in different directions. The current results are discussed in terms of previous proposals for the functional roles of these regions in activating, monitoring, and task setting, and the relation of these findings to the disparate reports in recent case series is considered. PMID- 20350182 TI - Neural correlates of sublexical processing in phonological working memory. AB - This study investigated links between working memory and speech processing systems. We used delayed pseudoword repetition in fMRI to investigate the neural correlates of sublexical structure in phonological working memory (pWM). We orthogonally varied the number of syllables and consonant clusters in auditory pseudowords and measured the neural responses to these manipulations under conditions of covert rehearsal (Experiment 1). A left-dominant network of temporal and motor cortex showed increased activity for longer items, with motor cortex only showing greater activity concomitant with adding consonant clusters. An individual-differences analysis revealed a significant positive relationship between activity in the angular gyrus and the hippocampus, and accuracy on pseudoword repetition. As models of pWM stipulate that its neural correlates should be activated during both perception and production/rehearsal [Buchsbaum, B. R., & D'Esposito, M. The search for the phonological store: From loop to convolution. Journal of Cognitive Neuroscience, 20, 762-778, 2008; Jacquemot, C., & Scott, S. K. What is the relationship between phonological short-term memory and speech processing? Trends in Cognitive Sciences, 10, 480-486, 2006; Baddeley, A. D., & Hitch, G. Working memory. In G. H. Bower (Ed.), The psychology of learning and motivation: Advances in research and theory (Vol. 8, pp. 47-89). New York: Academic Press, 1974], we further assessed the effects of the two factors in a separate passive listening experiment (Experiment 2). In this experiment, the effect of the number of syllables was concentrated in posterior-medial regions of the supratemporal plane bilaterally, although there was no evidence of a significant response to added clusters. Taken together, the results identify the planum temporale as a key region in pWM; within this region, representations are likely to take the form of auditory or audiomotor "templates" or "chunks" at the level of the syllable [Papoutsi, M., de Zwart, J. A., Jansma, J. M., Pickering, M. J., Bednar, J. A., & Horwitz, B. From phonemes to articulatory codes: an fMRI study of the role of Broca's area in speech production. Cerebral Cortex, 19, 2156-2165, 2009; Warren, J. E., Wise, R. J. S., & Warren, J. D. Sounds do-able: auditory-motor transformations and the posterior temporal plane. Trends in Neurosciences, 28, 636-643, 2005; Griffiths, T. D., & Warren, J. D. The planum temporale as a computational hub. Trends in Neurosciences, 25, 348-353, 2002], whereas more lateral structures on the STG may deal with phonetic analysis of the auditory input [Hickok, G. The functional neuroanatomy of language. Physics of Life Reviews, 6, 121-143, 2009]. PMID- 20350184 TI - Overrecruitment in the aging brain as a function of task demands: evidence for a compensatory view. AB - This study used fMRI to investigate the neural effects of increasing cognitive demands in normal aging and their role for performance. Simple and complex go/no go tasks were used with two versus eight colored letters as go stimuli, respectively. In both tasks, no-go stimuli could produce high conflict (same letter, different color) or low conflict (colored numbers) with go stimuli. Multivariate partial least square analysis of fMRI data showed that older adults overengaged a cohesive pattern of fronto-parietal regions with no-go stimuli under the specific combination of factors which progressively amplified task demands: high conflict no-go trials in the first phase of the complex task. This early neural overrecruitment was positively correlated with a lower error rate in the older group. Thus, the present data suggest that age-related extra recruitment of neural resources can be beneficial for performance under taxing task conditions, such as when novel, weak, and complex rules have to be acquired. PMID- 20350185 TI - Phonological neighborhood effects in spoken word production: an fMRI study. AB - The current study examined the neural systems underlying lexically conditioned phonetic variation in spoken word production. Participants were asked to read aloud singly presented words, which either had a voiced minimal pair (MP) neighbor (e.g., cape) or lacked a minimal pair (NMP) neighbor (e.g., cake). The voiced neighbor never appeared in the stimulus set. Behavioral results showed longer voice-onset time for MP target words, replicating earlier behavioral results [Baese-Berk, M., & Goldrick, M. Mechanisms of interaction in speech production. Language and Cognitive Processes, 24, 527-554, 2009]. fMRI results revealed reduced activation for MP words compared to NMP words in a network including left posterior superior temporal gyrus, the supramarginal gyrus, inferior frontal gyrus, and precentral gyrus. These findings support cascade models of spoken word production and show that neural activation at the lexical level modulates activation in those brain regions involved in lexical selection, phonological planning, and, ultimately, motor plans for production. The facilitatory effects for words with MP neighbors suggest that competition effects reflect the overlap inherent in the phonological representation of the target word and its MP neighbor. PMID- 20350186 TI - Role for presupplementary motor area in inhibition of cognitive set interference. AB - Proactive interference (PI), which is formed through repetition of certain behavior and lasts for a while, needs to be inhibited in order for subsequent behavior to prevail over the antecedent one. Although the inhibitory mechanisms in the pFC have been reported that are recruited long after one behavior is updated to another, very little is known about the inhibitory mechanisms that are recruited immediately after the update. The WCST was modified in the present fMRI study such that inhibition of PI could be examined both immediately after and long after update of behavior. Use of "dual-match" stimuli allowed us to compare two types of trials where inhibition of PI was and was not required (control and release trials, respectively). Significant activation was observed in the left pre-SMA during control versus release trials. The pre-SMA activation was selective to PI inhibition required immediately after update of behavior, which exhibited marked contrast to the left anterior prefrontal activation selective to PI inhibition required long after the update. These results reveal dissociable inhibitory mechanisms in these two regions that are recruited in the different temporal contexts of the inhibitory demands imposed during performance of the task. PMID- 20350188 TI - What iconic gesture fragments reveal about gesture-speech integration: when synchrony is lost, memory can help. AB - The present series of experiments explores several issues related to gesture speech integration and synchrony during sentence processing. To be able to more precisely manipulate gesture-speech synchrony, we used gesture fragments instead of complete gestures, thereby avoiding the usual long temporal overlap of gestures with their coexpressive speech. In a pretest, the minimal duration of an iconic gesture fragment needed to disambiguate a homonym (i.e., disambiguation point) was therefore identified. In three subsequent ERP experiments, we then investigated whether the gesture information available at the disambiguation point has immediate as well as delayed consequences on the processing of a temporarily ambiguous spoken sentence, and whether these gesture-speech integration processes are susceptible to temporal synchrony. Experiment 1, which used asynchronous stimuli as well as an explicit task, showed clear N400 effects at the homonym as well as at the target word presented further downstream, suggesting that asynchrony does not prevent integration under explicit task conditions. No such effects were found when asynchronous stimuli were presented using a more shallow task (Experiment 2). Finally, when gesture fragment and homonym were synchronous, similar results as in Experiment 1 were found, even under shallow task conditions (Experiment 3). We conclude that when iconic gesture fragments and speech are in synchrony, their interaction is more or less automatic. When they are not, more controlled, active memory processes are necessary to be able to combine the gesture fragment and speech context in such a way that the homonym is disambiguated correctly. PMID- 20350187 TI - From agents to objects: sexist attitudes and neural responses to sexualized targets. AB - Agency attribution is a hallmark of mind perception; thus, diminished attributions of agency may disrupt social-cognition processes typically elicited by human targets. The current studies examine the effect of perceivers' sexist attitudes on associations of agency with, and neural responses to, images of sexualized and clothed men and women. In Study 1, male (but not female) participants with higher hostile sexism scores more quickly associated sexualized women with first-person action verbs ("handle") and clothed women with third person action verbs ("handles") than the inverse, as compared to their less sexist peers. In Study 2, hostile sexism correlated negatively with activation of regions associated with mental state attribution-medial prefrontal cortex, posterior cingulate, temporal poles-but only when viewing sexualized women. Heterosexual men best recognized images of sexualized female bodies (but not faces), as compared with other targets' bodies; however, neither face nor body recognition was related to hostile sexism, suggesting that the fMRI findings are not explained by more or less attention to sexualized female targets. Diminished mental state attribution is not unique to targets that people prefer to avoid, as in dehumanization of stigmatized people. The current studies demonstrate that appetitive social targets may elicit a similar response depending on perceivers' attitudes toward them. PMID- 20350189 TI - Antibodies to chondroitin sulfate A-binding infected erythrocytes: dynamics and protection during pregnancy in women receiving intermittent preventive treatment. AB - BACKGROUND: Plasmodium falciparum parasites that cause malaria in pregnancy express unique variant surface antigens (VSAs). Levels of immunoglobulin G (IgG) antibody to pregnancy-associated VSAs measured at delivery are gravidity dependent, and they have been associated with protection from disease. It is not known how these IgG responses develop in pregnant women receiving intermittent preventive treatment during pregnancy (IPTp) or whether IgG levels in early pregnancy predict pregnancy outcomes. METHODS: We performed longitudinal measurements of IgG antibody to VSAs by flow cytometric analysis of serum samples obtained from 549 Malawian women receiving IPTp. We examined fluctuations in IgG levels over time and associated the IgG levels noted at study enrollment with clinical outcomes. RESULTS: Levels of IgG antibody to pregnancy-associated VSAs were gravidity dependent. Overall, levels decreased while women were receiving IPTp, but the levels of the individuals were highly dynamic. Primigravidae developed low levels of pregnancy-specific IgG, which were often boosted during second pregnancies. The prevalence of parasites was low (8.4% at enrollment and 2.4% in late pregnancy). Antibody levels at enrollment did not predict birth weight, duration of gestation at delivery, or the maternal hemoglobin level in late pregnancy. CONCLUSION: Levels of IgG antibody to pregnancy-specific VSAs decrease during receipt of IPTp. Antibody levels in early pregnancy did not predict clinical outcome. IPTp and decreasing malaria prevalence pose challenges for the evaluation of novel interventions for malaria during pregnancy. PMID- 20350190 TI - Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax. AB - BACKGROUND: Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax). METHODS: Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization. Subjects were followed up for clinical take, viral shedding, and immune responses. RESULTS: MVA administration attenuated clinical takes in 21 (72%) of 29 subjects, compared with 0 of 7 placebo recipients (P = .001). Attenuation was most significant in MVA groups that received 1 x 10(7) median tissue culture infective doses (TCID(50)) intradermally (P = .001) and 1 x 10(7) TCID(50) intramuscularly (P = .001). Both duration and peak titer of viral shedding were reduced in MVA recipients. Peak neutralizing antibody responses to vaccinia virus or MVA previously induced by MVA immunization were associated with attenuated takes (P = .02) and reduced duration (P = .001) and titer (P = .005) of viral shedding. CONCLUSIONS: MVA immunization results in clinical and virologic protection against Dryvax challenge. Protection is associated with prior induction of neutralizing antibodies to MVA or vaccinia virus. MVA administered intradermally has protective and immunologic responses similar to those of a 10-fold-higher dose given subcutaneously. PMID- 20350192 TI - High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in western Cambodia. AB - In western Cambodia, malaria parasites clear slowly from the blood after treatment with artemisinin derivatives, but it is unclear whether this results from parasite, host, or other factors specific to this population. We measured heritability of clearance rate by evaluating patients infected with identical or nonidentical parasite genotypes, using methods analogous to human twin studies. A substantial proportion (56%-58%) of the variation in clearance rate is explained by parasite genetics. This has 2 important implications: (1) selection with artemisinin derivatives will tend to drive resistance spread and (2) because heritability is high, the genes underlying parasite clearance rate may be identified by genome-wide association. PMID- 20350191 TI - Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration. AB - BACKGROUND: We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration. METHODS: Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart. RESULTS: MVA was generally well tolerated at all dose levels and by all routes. More pronounced local reactogenicity was seen with the intradermal and subcutaneous routes than with intramuscular administration. Binding antibodies to whole virus and neutralizing antibodies to the intracellular mature virion and extracellular enveloped virion forms of vaccinia virus were elicited by all routes of MVA administration and were greater for the higher dose by each route. Similar levels of neutralizing antibodies were seen at a 10-fold-lower dose given intradermally (1 x 10(7) median tissue culture infective doses [TCID(50)]), compared with responses after 1 x 10(8) TCID(50) given intramuscularly or subcutaneously. T cell immune responses to vaccinia virus were detected by an interferon gamma enzyme-linked immunospot assay but had no clear relationship to dose or route. CONCLUSIONS: These data suggest that intradermal immunization with MVA provides a dose-sparing effect by eliciting antibody responses similar in magnitude and kinetics to those elicited by the intramuscular or subcutaneous routes but at a 10-fold-lower dose. PMID- 20350193 TI - Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. AB - BACKGROUND: Because of its wide spectrum of clinical manifestations and its well defined immunological complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene, for a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes. METHODS: We used a case-control study design with 933 patients in Nepal. Our study included 240 patients with type 1 (reversal) reactions and 124 patients with type 2 (erythema nodosum leprosum) reactions. We compared the frequencies of 32 common polymorphisms in the NOD2 gene region between patients with the different clinical types of leprosy as well as between the patients and 101 control participants without leprosy. RESULTS: Four polymorphisms were associated with susceptibility to leprosy when comparing allele frequencies, and 8 were associated when comparing genotype frequencies with a dominant model. Five polymorphisms were associated with protection from reversal reaction in an allelic analysis, and 7 were associated with reversal reaction with a dominant model. Four polymorphisms were associated with increased susceptibility to erythema nodosum leprosum in an allelic analysis, whereas 7 of 32 polymorphisms were associated with a dominant model. CONCLUSION: These data suggest that NOD2 genetic variants are associated with susceptibility to leprosy and the development of leprosy reactive states. PMID- 20350195 TI - Parasitic diseases: chemotherapy with a twist. PMID- 20350194 TI - Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. AB - BACKGROUND: Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed. METHODS: We conducted a randomized, exploratory open-label trial to assess the efficacy and safety of mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), mefloquine-artesunate (3 doses of 100 mg artesunate plus 250 mg mefloquine), and praziquantel (40 mg/kg) against Schistosoma haematobium. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined. RESULTS: A total of 83 S. haematobium infected schoolchildren were included in the study. Cure rates of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against S. haematobium at day 26 after treatment were 21%, 25%, 61%, and 88%, respectively. Both mefloquine artesunate and praziquantel resulted in egg reduction rates >95%. Significantly lower egg reduction rates were seen in the artesunate (85%) and mefloquine groups (74%). In children coinfected with S. mansoni, praziquantel and mefloquine artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-artesunate completely cured infections due to Plasmodium falciparum. No effects were found against soil-transmitted helminths and intestinal protozoa. Abdominal pain was the most frequent adverse event, with a higher incidence among children treated with mefloquine (89%), mefloquine-artesunate (83%), and artesunate (60%) than among children treated with praziquantel (46%). CONCLUSIONS: The high efficacy of mefloquine-artesunate against S. haematobium warrants further investigation. Individuals coinfected with Plasmodium and Schistosoma who were treated with a mefloquine-artesunate combination against malaria might have a dual benefit: clearance of malaria parasitemia and reduction of schistosomiasis-related morbidity. CLINICAL TRIALS REGISTRATION: Current Controlled Trials identifier: ISRCTN06498763. PMID- 20350196 TI - Coronavirus survival on healthcare personal protective equipment. PMID- 20350197 TI - Trial of universal gloving with emollient-impregnated gloves to promote skin health and prevent the transmission of multidrug-resistant organisms in a surgical intensive care unit. AB - OBJECTIVE: To compare the efficacy of universal gloving with emollient impregnated gloves with standard contact precautions for the control of multidrug resistant organisms (MDROs) and to measure the effect on healthcare workers' (HCWs') hand skin health. DESIGN: Prospective before-after trial. SETTING: An 18 bed surgical intensive care unit. METHODS: During phase 1 (September 2007 through March 2008) standard contact precautions were used. During phase 2 (March 2008 through September 2008) universal gloving with emollient-impregnated gloves was used, and no contact precautions. Patients were screened for vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). HCW hand hygiene compliance and hand skin health and microbial contamination were assessed. The incidences of device-associated infection and Clostridium difficile infection (CDI) were determined. RESULTS: The rate of compliance with contact precautions (phase 1) was 67%, and the rate of compliance with universal gloving (phase 2) was 78% (P = .01). Hand hygiene compliance was higher during phase 2 than during phase 1 (before patient care, 40% vs 35% of encounters; P = .001; after patient care, 63% vs 51% of encounters; P < .001). No difference was observed in MDRO acquisition. During phases 1 and 2, incidences of device-related infections, in number of infections per 1,000 device-days, were, respectively, 3.7 and 2.6 for bloodstream infection (P = .10), 8.9 and 7.8 for urinary tract infection (P = .10), and 1.0 and 1.1 for ventilator-associated pneumonia (P = .09). The CDI incidence in phase 1 and in phase 2 was, respectively, 2.0 and 1.4 cases per 1,000 patient-days (P = .53). During phase 1, 29% of HCW hand cultures were MRSA positive, compared with 13% during phase 2 (P = .17); during phase 1, 2% of hand cultures were VRE positive, compared with 0 during phase 2 (P = .16). Hand skin health improved during phase 2. CONCLUSIONS: Compared with contact precautions, universal gloving with emollient-impregnated gloves was associated with improved hand hygiene compliance and skin health. No statistically significant change in the rates of device-associated infection, CDI, or patient MDRO acquisition was observed. Universal gloving may be an alternative to contact precautions. PMID- 20350198 TI - Lack of preparation, physical health after childbirth, and early postpartum depressive symptoms. AB - BACKGROUND: Prior research has not examined the association of patient expectations or preparation by providers for the postpartum experience with depressive symptoms. We investigated whether lack of preparation for the postpartum experience and physical health after uncomplicated childbirth were associated with early postpartum depressive symptoms. METHODS: We conducted a telephone survey of 720 early postpartum mothers in New York City. Mothers reported on depressive symptoms, physical symptoms, provider preparation for the postpartum experience, and other factors. RESULTS: Nearly 39% of patients reported depressive symptoms; 24% did not feel adequately prepared by their provider for the postpartum experience. Mothers reported a range of physical symptoms: 98% reported daily vaginal bleeding, 79% reported cesarean section or episiotomy site pain, 82% reported breast pain, and 32% reported urinary incontinence. Patients who reported inadequate preparation by their provider were more likely to report depressive symptoms compared with patients who reported adequate preparation (53% vs. 35%, p < 0.001). In a multivariable model predicting postpartum depressive symptoms, adjusted odds ratios (ORs) remained elevated for perceived lack of preparation for the postpartum experience, more physical symptoms, and more physical functional limitations. CONCLUSIONS: Further research is needed to investigate whether preparing patients for expected health consequences after pregnancy may reduce the incidence of early postpartum depressive symptoms. PMID- 20350199 TI - Content analysis of continuing medical education for cervical cancer screening. AB - BACKGROUND: Since 2003, newer cervical cancer screening guidelines that include human papillomavirus (HPV) testing with cytology (HPV co-testing) call for extension of screening intervals in women who are cytology normal and HPV negative. Continuing medical education (CME) may help increase knowledge and appropriate adoption of new technologies and guidelines. However, there are concerns that industry support of CME may bias messages favoring newer technologies without emphasizing the updated guidelines, especially less frequent testing recommendations. Our objectives were to assess availability and accuracy of web-based CME activities describing cervical cancer screening guidelines, screening intervals, and HPV testing. METHODS: We identified 20 web-based CME activities available between 2006 and 2008 and evaluated the content for messages related to HPV and natural history, cervical cancer screening guidelines, management of HPV abnormalities, and counseling tips for patients. In addition to content, we noted funding source, credit offered, and dates available. RESULTS: Most activities (80%) discussed the updated screening guidelines with HPV co testing for eligible women. Twelve activities (60%) referenced professional organization support of the extended screening interval with the HPV co-test, and three (15%) discussed the justification for extension of intervals for eligible women. Eight activities (40%) were funded by industry, seven of which included accurate, updated screening guidelines about extension of screening intervals. CONCLUSIONS: Web-based CME activities generally support updated guidance for HPV co-testing and extended screening intervals but need more information on counseling patients and acceptability of extending screening intervals. PMID- 20350202 TI - Applications of robotic surgery in gynecology. AB - This article reviews the applications of robotic surgery in gynecology and presents a summary of the early studies that have been performed regarding its use for hysterectomy, myomectomy, reproductive surgery, pelvic floor reconstruction, and gynecological cancer staging. Despite significant advances in conventional laparoscopic techniques, the majority of gynecological procedures are still performed through major abdominal incisions, which are associated with higher surgical morbidity. This article addresses the potential that robotic surgery may have in converting more gynecological operations to a minimally invasive approach. PMID- 20350203 TI - Age, menopause, and cardiovascular risk factors among korean middle-aged women: the 2005 Korea National Health and Nutrition Examination Survey. AB - OBJECTIVE: This study examined the effects of menopause and age on cardiovascular disease (CVD) risk factors in a nationally representative sample of middle-aged Korean women. METHODS: This study used the data of 1169 perimenopausal Korean women (mean age 50.1 +/- 7.2 years, 44% postmenopausal) from the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). Menopausal status was confirmed by self-reports. Risk factors of CVD included reported lifestyle characteristics (smoking, physical activity level, and dietary and alcohol intake) and measured anthropometry, blood pressure, fasting glucose, and serum lipid levels. Sociodemographic characteristics and general health conditions were assessed by interviews. Descriptive statistics and multiple regression models were used to assess the effects of age and menopause on various CVD risk factors. RESULTS: The mean age of natural menopause in Korean women was 50.2 +/- 3.7 years. Lifestyle risk factors of CVD were not significantly different by menopausal status or age except the percent of energy intake from fat, which decreased by menopause and age. Waist circumference increased with both age and menopause; blood pressure was elevated only with age, and serum lipids were associated only with menopausal status. However, fasting serum glucose was not related to either age or menopausal status. CONCLUSIONS: This study showed the increasing CVD risk burdens with menopause and aging in Korean middle-aged women. More study is warranted to better understand ways to attenuate the deleterious changes. PMID- 20350200 TI - Protective effect of melatonin upon neuropathology, striatal function, and memory ability after intracerebral hemorrhage in rats. AB - Since free radicals play a role in the mechanisms of brain injury after hemorrhagic stroke, the effect of melatonin (a potent antioxidant and free radical scavenger) on outcomes was investigated after intracerebral hemorrhage (ICH) in rats. ICH was induced by clostridial collagenase infusion into the right caudate putamen, and several time points and doses of melatonin were studied. Brain edema and neurological function at 24 h were unchanged in comparison with vehicle-treated groups, in spite of oxidative stress reductions. Repeated treatment with the lower dose of melatonin (5 mg/kg) given at 1 h and every 24 h thereafter for 3 days after ICH, led to normalization of striatal function and memory ability over the course of 8 weeks, and less brain atrophy 2 weeks later. These results suggest that melatonin is safe for use after ICH, reduces oxidative stress, provides brain protection, and could be used for future investigations of free radical mechanisms after cerebral hemorrhage. PMID- 20350204 TI - Physical dating violence victimization in college women in Chile. AB - OBJECTIVES: There are no published studies on physical dating violence in college students in Chile, and campuses across the country currently lack systematized programs to prevent or respond to this public health problem. This is the first study to examine prevalence and predictors of physical dating violence victimization with a sample of female college students in Chile. METHODS: A closed-ended questionnaire was administered to students enrolled in general education courses at a major public university. The prevalence of women's physical dating violence victimization was calculated, and generalized ordered logit models were used to estimate risk factors for such victimization (n = 441). Ancillary analyses examined associations of dating violence victimization with experiences of unwanted sexual contact and forced condom nonuse. RESULTS: Approximately 21% of subjects reported one or more incidents of physical dating violence not involving physical injury since age 14, and another 5% reported at least one incident resulting in physical injury during this time period. Risk factors identified in five sequential models were sexual abuse and witnessing of domestic violence in childhood, low parental education, residence away from the parental home, urban residence, and having had sexual intercourse. Maternal employment and religious participation had protective effects. Dating violence victimization was found to be significantly associated with experiences of unwanted sexual contact and forced condom nonuse. CONCLUSIONS: The study findings show a high prevalence of physical dating violence, strong associations between several sociodemographic factors and dating violence, and links between dating violence and sexual/reproductive risk. Our results indicate a need to expand attention to this public health problem in Chile as well as other developing countries, where research and prevention/response initiatives have generally been similarly limited. The findings also have important implications for the content of dating violence, HIV/sexually transmitted infection (STI), and pregnancy prevention programs for adolescents and young adults. PMID- 20350205 TI - Oral contraceptive use among women in the military and the general U.S. population. AB - OBJECTIVE: To compare oral contraceptive (OC) use during a 12-month period among women aged 18-39 years in the U.S. military and the general U.S. population using data from the Military Health System Management Analysis and Reporting Tool (M2) and the National Health and Nutrition Examination Survey (NHANES), respectively. METHODS: OC use was age adjusted to the 2000 U.S. Census population. Comparisons between the military (n = 83,181) and the general population (unweighted n = 360), as well as between the military branches, were conducted overall and stratified by age, race/ethnicity, and marital status. RESULTS: OC use was higher in the military (34%) than in the general population (29%, p < 0.05). This difference increased with age and was most pronounced among Hispanics (military, 32.2%; general population, 19.8%). Within the military, OC use was highest in the Air Force (39%) and lowest in the Army (30%, p < 0.05). CONCLUSIONS: These findings suggest that OC use differs between the military and the general population and within the military by service branch. Further studies that assess whether OC use is related to variations in health outcomes between these two populations and within the military are warranted. PMID- 20350206 TI - Colorectal cancer screening compliance and contemplation in gynecology patients. AB - OBJECTIVE: Colorectal cancer screening (CRCS) should be a necessary part of gynecology (GYN) providers' preventive practices. The purpose of our study is to examine CRCS recommendations and adherence in this population. METHODS: A questionnaire was administered to a prospective cohort of patients awaiting health maintenance exams at six academic and private gynecology offices. Patients reported demographics, CRC/breast/cervical screening adherence, CRCS recommendations, and future likelihood of CRCS. RESULTS: A total of 461 women aged 51 years and older completed the questionnaire. Sixty-six percent of respondents were compliant with CRCS compared to 93% and 86% for breast and cervical cancer screening, respectively (p < 0.001). GYN providers recommended CRCS in 43% of patients. Sixty-three percent were planning to undergo future CRCS. On multivariable analysis, characteristics associated with CRCS adherence included (odds ratio, 95% confidence interval): older age (1.1 per year, 1.1 1.2), previous mammography (3.7, 1.4-9.7), family history (FH) of CRC/polyps (1.9, 1.0-3.4), friend with CRC (2.6, 1.5-4.7), and any doctor recommending CRCS (8.2, 4.6-14.7). CRCS rates were higher among patients who received a recommendation from a PCP (primary care provider) than from a GYN provider. Factors associated with intention to undergo CRCS include previous mammography (1.4, 4.2-12.0), any doctor recommendation (6.4, 3.7-11.0), and FH of CRC/polyps (3.5, 1.9-6.3). CRCS recommendations by both GYNs and PCPs had a greater impact on CRCS contemplation than those from a PCP or GYN alone. CONCLUSION: In gynecology patients, having multiple providers recommend CRCS increases the likelihood of patients' intentions to undergo CRCS. However, CRCS compliance is primarily driven solely by PCP recommendations. Regardless, strategies must be in place to prompt gynecologists and nurse practitioners to discuss CRCS in eligible patients. PMID- 20350207 TI - Perceived sexism as a health determinant in Spain. AB - OBJECTIVES: The goals of the present study are to explore the association between perceived sexism and self-perceived health, health-related behaviors, and unmet medical care needs among women in Spain; to analyze whether higher levels of discrimination are associated with higher prevalence of poor health indicators and to examine whether these relationships are modified by country of origin and social class. MATERIALS AND METHODS: The study is based on a cross-sectional design using data from the 2006 Spanish Health Interview Survey. We included women aged 20-64 years (n = 10,927). Six dependent variables were examined: four of health (self-perceived health, mental health, hypertension, and having had an injury during the previous year), one health behavior (smoking), and another related to the use of the health services (unmet need for medical care). Perceived sexism was the main independent variable. Social class and country of origin were considered as effect modifiers. We obtained the prevalence of perceived sexism. Logistic regression models, adjusted for potential confounders, were fitted to study the association between sexism and poor health outcomes. RESULTS: The prevalence of perceived sexism was 3.4%. Perceived sexism showed positive and consistent associations with four poor health outcomes (poor self perceived health, poor mental health, injuries in the last 12 months, and smoking). The strength of these associations increased with increased scores for perceived sexism, and the patterns were found to be modified by country of origin and social class. CONCLUSION: This study shows a consistent association between perceived sexism and poor health outcomes in a country of southern Europe with a strong patriarchal tradition. PMID- 20350208 TI - Whiplash patients' experience of a multimodal rehabilitation programme and its usefulness one year later. AB - OBJECTIVE: The study aimed to explore and analyse how, 1 year after completing a rehabilitation programme, persons with long-term pain due to whiplash-associated disorders (WAD) experienced their participation, and what knowledge and strategies they had gained from it for handling their daily occupations. METHODS: The study had an emergent design. Thematised research interviews were conducted with nine informants. The results were analysed according to the constant comparison grounded-theory method. RESULTS: Data analysis resulted in one core category, 'learning to manage WAD, a rehabilitation process', and three associated categories: 'chaos in life', 'a light in the tunnel' and 'managing long-term pain'. The core category and the categories describe the process the informants underwent from how they experienced life when starting rehabilitation to one year after completion. CONCLUSION: The informants described living with long-term whiplash-associated pain as 'chaos' before the rehabilitation programme. Participation helped them realise that there was a possible way for them to control their pain, regain their daily occupation and return to work. One year after rehabilitation the informants had started to accept their situation and regain occupations and life roles. PMID- 20350209 TI - Rehabilitation of postural stability in ataxic/hemiplegic patients after stroke. AB - PURPOSE: This study assesses the postural stability and the effect of balance training using a force platform visual biofeedback among outpatients with postural disturbances following stroke. METHOD: A tilting multiaxial force platform was used to assess bilateral postural stability in 38 outpatients (mean age 69.50 +/- 8.57 years) with hemiplegia and/or ataxia after stroke. Stability indexes were obtained. Afterwards, a subgroup of 12 patients with the poorest overall stability index (OASI) started a balance training programme in the force platform. Postural control training consisted of a 30-min training session once a week for a 15-week period. The test was then repeated. RESULTS: In the 38 outpatients sample, the mean OASI was 4.7 +/- 2.0 and 42.1% of the patients used their hands for support. In the 12 outpatients group, the initial OASI was 5.8 +/- 2.3 and half of the patients used their hands for support. The final OASI was 3.3 +/- 1.0 (p = 0.005) and only two of the patients used their hands for support (p = 0.046). CONCLUSION: Our results suggest that a training programme using force platform visual biofeedback improves objective measures of bilateral postural stability in patients with hemiplegia and/or ataxia after stroke. PMID- 20350210 TI - Objectivity in image analysis. PMID- 20350211 TI - On the concept of objectivity in digital image analysis in pathology. AB - AIMS: The term 'objective' connotes a method that is based on facts and not influenced by personal opinions, perception or emotion. One often reads in the biomedical literature claims of objectivity for methods that use digital image analysis applied to histology. Since objective assessment of histology would represent a huge leap forward in scientific measurement and clinical diagnosis, such claims should be substantiated by strong evidence. This paper takes a selective look at the literature on image analysis to assess the definition of objectivity in image analysis and asks whether such a claim is ever justified. METHODS: First, a brief background on the basic science of image analysis in histology details some of the controversies and opinions in the field. Then, a literature review of a subset of papers pertaining to image analysis in histology (with claims of objectivity) is conducted to determine what evidence exists for objectivity in these methods. RESULTS: It was found that image analysis may have many benefits (speed, indefatigability, standardisation, etc.). However, algorithms are devised and implemented by human beings who make subjective decisions at each stage of the algorithm design and implementation process. Thus, image analysis methods can be seen as deterministic processes which 'objectively' implement the subjective decisions of the programmer. This indicates that 'inter observer' variation in image analysis is equivalent to 'inter-algorithm' variation (which is rarely studied) and that a single computer algorithm's repeatability is of lesser importance than the repeatability of the image analysis method as a whole (including the block, slide and field selection and the method of tissue processing). CONCLUSION: Repeatability and automaticity must not be confused with objectivity, but a lack of objectivity does not imply a lack of utility. Unless specific evidence of objectivity is provided, editors should insist that claims of objectivity in image analysis papers be either removed or justified prior to publication. PMID- 20350212 TI - Pseudonegative BCL2 protein expression in a t(14;18) translocation positive lymphoma cell line: a need for an alternative BCL2 antibody. AB - AIM: The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein expression in most follicular lymphomas. However, a small number of cases lack BCL2 expression despite carrying the t(14;18)(q32;q21) translocation. This study aims to explore the mechanism accounting for the lack of BCL2 protein expression when the t(14;18) translocation is present. METHODS: BCL2 expression in the t(14;18) positive cell lines FL18, Karpas-422, SU-DHL-4 and SU-DHL-6, was analysed by Western blotting and by immunohistochemistry using two different antibodies. FISH analysis was performed to confirm the cytogenetic changes in the cell lines and real time quantitative PCR was used to evaluate the BCL2 mRNA level. Sequence analysis of translocated BCL2 was performed on FL18, Karpas-422, SU-DHL-4 and SU-DHL-6 cell lines. RESULTS: In FL18, Karpas-422, and SU-DHL-4, the BCL2 mRNA level correlated with the BCL2 protein expression. In contrast, BCL2 protein was not detected in SU-DHL-6 line using standard anti-BCL2 antibody (BCL2/124), despite the presence of the t(14;18) translocation and high level of mRNA. cDNA sequencing of translocated BCL2 showed three mutations in the SU-DHL-6 cell line, one of which resulted in an amino acid substitution (I48F) in the region recognised by the standard BCL2 antibody, whereas the other two were silent mutations at aa71 and aa72. Interestingly, when BCL2 expression was tested with an alternative antibody, E17, the protein was detected in SU-DHL-6, suggesting that the 'negativity' of SU-DHL-6 line for BCL2 using the standard antibody is spurious. Amino acid changes were found in Karpas-422 (G47D, P59L) and SU-DHL-4 (P59T, S117R) but these did not affect BCL2 detection. CONCLUSIONS: This study suggests that some somatic mutations of the translocated BCL2 gene may prevent epitope recognition by BCL2 antibodies, and hence cause false negative expression using the standard antibody. It is recommended that in practice all BCL2 negative cases should routinely be stained with an alternative antibody to prevent false negativity. PMID- 20350213 TI - Diagnostic value and implications of vimentin expression in normal, reactive and neoplastic endocervical epithelium. AB - AIMS: To assess vimentin immunoreactivity in normal, reactive and neoplastic endocervical epithelium, and compare the results with p16 protein, Ki-67 and bcl 2 expression. METHODS: Sixty-two cervical biopsy specimens including normal endocervical epithelium, tubo-endometrioid metaplasia, adenocarcinoma in situ, stratified mucin producing intraepithelial lesions (SMILE), and invasive adenocarcinomas were stained immunohistochemically for vimentin and for p16 protein, Ki-67 and bcl-2. Twelve cases also included areas of high grade cervical intraepithelial neoplasia (CIN). RESULTS: Normal endocervical epithelium usually showed subtle but distinct sub-nuclear and delicate lateral cell border vimentin expression while tubo-endometrioid metaplasia exhibited more diffuse cytoplasmic immunoreactivity. Usually adenocarcinoma in situ was completely negative and therefore vimentin staining sharply distinguished the benign and neoplastic epithelial elements. The SMILE lesions and high grade CIN were also vimentin negative in most cases. Most invasive adenocarcinomas were not stained but focal vimentin immunoreactivity was observed in 7/18 cases, and was restricted to small glands and infiltrating cell clusters at the deep (advancing) tumour margin. CONCLUSIONS: Normal endocervical cells often exhibit vimentin staining, and this is increased in reactive and metaplastic situations, whereas adenocarcinoma in situ is usually completely negative. Therefore vimentin is a useful additional diagnostic marker in the assessment of problematic cervical glandular lesions. The localised re-expression of vimentin at the deep margin of some endocervical adenocarcinomas may be relevant to the process of tumour progression and invasion in these cases. PMID- 20350214 TI - Diagnostic value of Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen levels in malignant pleural effusions of lung adenocarcinoma. AB - AIMS: Cytology fails to detect neoplastic cells in 40-50% of cases of malignant pleural effusion, a condition that frequently accompanies lung adenocarcinoma. Published reports of diagnostic sensitivity of various tumour markers are inconsistent, and optimal cut-off points have not been determined. This study aimed to evaluate the ability of three markers to discriminate lung adenocarcinoma-associated malignant pleural effusion (LAC-MPE) from benign effusion. METHODS: Pleural effusion samples were collected from 41 patients with LAC-MPE, and from 93 with various benign conditions. The diagnostic sensitivity and specificity for Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen (CEA) were evaluated. Cut-off points for these markers are optimally set at 3.6 microg/L, 60 microg/L, and 6.0 microg/L, respectively. RESULTS: Her-2/neu, Cyfra 21-1, and CEA vary in their diagnostic accuracy to differentiate LAC-MPE from benign pleural effusion: 79.85%, 88.81%, and 94.03%, respectively. CEA combined with Cyfra 21-1 increases diagnostic sensitivity to 97.6%, with a specificity of 91.4%. CONCLUSIONS: With appropriate cut-off points, CEA currently provides the best diagnostic accuracy. Combining CEA with Cyfra 21-1 increases diagnostic sensitivity to nearly 100%. The results of the present study may help clinicians decide whether to obtain a cytological/histological specimen by invasive means to investigate a possible diagnosis of malignancy. PMID- 20350216 TI - Primary colorectal inflammatory myofibroblastic tumour: a clinicopathological and immunohistochemical study of seven cases. AB - AIMS: Primary colorectal inflammatory myofibroblastic tumours are rare. Here we report seven such cases to demonstrate their clinicopathological features and prognosis. METHODS: Clinical and pathological data of seven cases of colorectal inflammatory myofibroblastic tumour were reviewed. Immunohistochemical staining was also performed. RESULTS: The presenting symptoms included abdominal or pelvic mass (7 patients), abdominal pain (7 patients), and lower gastrointestinal haemorrhage (2 patients). The tumour size ranged from 3.8 cm to 6.3 cm in greatest dimension. Histologically these tumours showed three patterns: myxoid hypocellular, fascicular, and hyalinised pattern. A lymphoplasmacytic infiltrate was present in all seven tumours. Mitotic figures were 0 approximately 2 per 10 high power fields (HPF) in five cases and were focally up to 4 approximately 6 per 10 HPF in two tumours. Nuclear atypia was mild in five and moderate focally in two tumours. Necrosis was absent. Anaplastic lymphoma kinase (ALK), smooth muscle actin, and vimentin staining were present in all tumours. S100, CD21, CD34, CD35, desmin, CK, CD68, and CD117 were negative in all inflammatory myofibroblastic tumours. The patients were followed up for 3-8 years (mean 4.9 years). Five patients were alive without evidence of disease after tumour resection. Two patients had a tumour recurrence 14 and 18 months after the initial surgery, respectively. A second surgical resection was performed for the recurrent tumours and the patients have been free of disease since (now 22 and 35 months after the second surgery, respectively). CONCLUSIONS: Colorectal inflammatory myofibroblastic tumours are rare, benign or low malignant tumours and ALK positivity is helpful in pathological diagnosis. PMID- 20350215 TI - Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN). AB - AIMS: Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis. METHODS: We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanIN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data. RESULTS: Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, PanIN-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanIN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 >5% correlated with reduced survival. CONCLUSIONS: In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 >5% independently predicted poor outcome. PMID- 20350217 TI - Expression of Smad and its signalling cascade in osteosarcoma. AB - AIMS: Smad signalling is important for inducing the expression of cell cycle inhibitors such as p21/WAF1, thereby facilitating transforming growth factor (TGF)-beta mediated inhibition of cell growth. The role and clinical implications of Smad signalling in osteosarcoma remain unclear. METHODS: We assessed the immunohistochemical expression profiles of Smad2, P-Smad2, Smad4, and p21/WAF1 proteins in 34 cases of osteosarcoma. We also investigated whether the expression of these proteins was correlated with clinicopathological parameters. RESULTS: The p21/WAF1 expression showed a significant relationship with tumour extension (p = 0.018). Smad4 expression was significantly correlated with Smad2 (p = 0.019) and P-Smad2 (p = 0.006) expression in osteosarcoma. Kaplan-Meier analysis showed that tumour extension (p = 0.0038), TNM stage (p = 0.0096), and p21/WAF1 expression (p = 0.0023) were significantly correlated with overall survival. Cox multivariate analysis showed that tumour extension (p = 0.048) and p21/WAF1 expression (p = 0.022) were independent poor prognostic factors. CONCLUSIONS: Smad signalling in osteosarcoma is partially operative. The high p21/WAF1 expression in osteosarcoma is significantly correlated with tumour extension. Our results suggest that overexpression of p21/WAF1 in osteosarcoma might be one of the poor prognostic factors. PMID- 20350218 TI - Expression of alpha-dystroglycan correlates with tumour grade and predicts survival in oral squamous cell carcinoma. AB - AIMS: Dystroglycan (DG) is a non-integrin adhesion molecule connecting the extracellular matrix to the actin cytoskeleton. Decreased expression of DG has been reported in several human cancers and related to tumour aggressiveness. METHODS: Expression of the alpha-DG subunit was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. RESULTS: Alpha-DG expression was easily detected in normal epithelium with a mean percentage of positive cells >80% but was undetectable in a significant fraction (59%) of OSCC. Loss of alpha-DG staining correlated with higher tumour grade (p = 0.04) and stage (p = 0.01), with nodal involvement (p = 0.001) and with an increased risk of recurrence (p = 0.002) and death (p = 0.004) in a univariate analysis, but it was not confirmed as an independent predictor of clinical outcome in a multivariate analysis. CONCLUSIONS: Loss of alpha-DG expression, which corresponds to loss of a functional DG complex, is a frequent event in human OSCC. Further studies are warranted on the role of this molecule in the entire multistep process of oral squamous tumorigenesis. PMID- 20350219 TI - The effect of feeding and fasting on fenestrations in the liver sinusoidal endothelial cell. AB - AIMS: Fenestrations are pores in the liver sinusoidal endothelial cell that facilitate the transfer of substrates between blood and hepatocytes. The aim of this study was to determine the effect of nutritional state on the morphology of fenestrations. METHODS: Scanning electron microscopy was used to investigate fenestrations in livers from fasted and fed rats. RESULTS: Fasting for 48 hours in rats was associated with an increase in the diameter of fenestrations from 90.7 +/- 11.7 nm in the fed state to 99.0 +/- 12.11 nm (p < 0.005). There was a concomitant reduction in the frequency of fenestrations from 8.45 +/- 2.43 to 7.39 +/- 2.28 fenestrations per microm(2) (p =0.05). CONCLUSIONS: Fasting was associated with increased diameter of fenestrations. The results provide evidence that fenestrations are dynamic structures that respond in vivo to physiological stimuli such as nutritional status. PMID- 20350220 TI - Role of the renal sympathetic nervous system in mediating renal ischaemic injury induced reductions in renal haemodynamic and excretory functions. AB - AIM: We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post ischaemic phase of renal ischaemia/reperfusion injury. METHODS: Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded. RESULTS: Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p < 0.05 vs innervated ARF rats). Potassium excretion was significantly lower in denervated group as per fractional (p < 0.05 vs innervated ARF rats) but not absolute potassium excretion (p > 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats). CONCLUSIONS: The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions. PMID- 20350221 TI - Three-year longitudinal study of genotypes of Mycobacterium tuberculosis in a low prevalence population. AB - OBJECTIVE: To investigate the molecular epidemiology of tuberculosis, temporal and spatial distribution of Mycobacterium tuberculosis isolates and associations between genotypes and clinical characteristics, in a low prevalence population. METHODS: A total of 930 M. tuberculosis isolates referred to the New South Wales (NSW, Australia) Mycobacterium Reference Laboratory in 2004-2006 were characterised by mycobacterial interspersed repetitive unit (MIRU) and spacer oligonucleotide (spoligo) typing. Associations between genotypes, patient age, disease site and drug resistance were explored and the predictive power of molecular typing was analysed using Bayesian Belief Networks. RESULTS: Among isolates from 855 NSW residents, there were 287 spoligotypes, 494 MIRU types and 643 unique spoligotype-MIRU type combinations. They formed 73 spoligotype, 104 MIRU type and 76 spoligo-MIRU clusters, most of which contained only two isolates. The majority (87.7%) of spoligotype clusters contained several MIRU profiles and 64.4% of MIRU clusters contained several spoligotypes. The three most common M. tuberculosis clades were Beijing (24.1%), East African Indian (11.8%) and Central Asian (6.5%); 6.9% and 0.7% isolates were resistant to isoniazid and rifampicin, respectively. There was no proof of association between genotype and drug resistance but isoniazid resistance increased independently over time. Given the low rates of genotype clustering, statistical analysis of genotype-phenotype associations was limited. Potential associations were not confirmed by Bayesian classifiers. CONCLUSIONS: Spoligo and MIRU typing demonstrated low levels of M. tuberculosis clustering in NSW; temporal and spatial changes in M. tuberculosis genotypes reflected migration patterns to Australia. No analytically significant associations between M. tuberculosis genotypes and clinical phenotypes were detected. PMID- 20350222 TI - Antimicrobial susceptibility of Moraxella catarrhalis isolated from children in Kalgoorlie-Boulder, Western Australia. AB - AIM: To investigate antimicrobial susceptibility of Moraxella catarrhalis isolated from a cohort of children being followed in a study of the natural history of otitis media in a semi-arid region of Western Australia. METHODS: In the Kalgoorlie Otitis Media Research Project nasopharyngeal aspirates were collected from children up to seven times between the age of 1 week and 2 years. A total of 261 M. catarrhalis strains from 50 Aboriginal and 50 non-Aboriginal children were tested against 14 antibiotics using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method. RESULTS: All strains were susceptible to amoxicillin/clavulanate, cefuroxime, azithromycin, ciprofloxacin, moxifloxacin, levofloxacin, erythromycin and minocycline. While no criteria exist for assessment of susceptibility to roxithromycin, minimum inhibitory concentrations (MICs) were low. Approximately 46% of strains from Aboriginal children and 27% from non-Aboriginal children appeared susceptible to ampicillin. A small number of strains was intermediately resistant to cefaclor (9/261, 3.4%), while the bulk of strains was intermediately resistant to co-trimoxazole. A low prevalence of tetracycline resistance (3/261, 1.1%) was noted. beta-lactamase production was observed in 97.7% of strains. CONCLUSIONS: While M. catarrhalis strains from children of the Kalgoorlie region were susceptible to many of the antibiotics used to treat respiratory tract infections, a large proportion of strains were resistant to ampicillin and/or co-trimoxazole. Current therapeutic guidelines, which recommend amoxicillin for treatment of otitis media, may need to be revised. PMID- 20350223 TI - A cost-effective method for the presumptive identification of Enterobacteriaceae for diagnostic microbiology laboratories. AB - AIMS: This study evaluated the use of an abbreviated algorithm for the presumptive identification of Enterobacteriaceae isolated from clinical microbiology specimens. METHODS: Identification was based on primary isolation of bacterial pathogens on blood, lactose fermentation based on colonial morphology on MacConkey agar, oxidase and indole tests, and a limited number of conventional biochemical tests. The accuracy of the study algorithm was prospectively evaluated against commercial bacterial identification kits, using clinical isolates from blood, urine and superficial wound and tissue sites. RESULTS: Of 534 isolates, 518 (97%) were accurately identified to genus level. Identification of the study isolates was achieved with a 56% reduction in technologist time and 85% reduction in reagent costs, when compared to the use of a conventional biochemical identification panel. The main limitation of the protocol in the tested bacterial population was that indole-negative Escherichia coli were likely to be misidentified as Enterobacter species. CONCLUSIONS: This protocol may be suitable for the presumptive identification of commonly isolated Enterobacteriaceae from non-sterile sites by diagnostic laboratories in resource constrained settings. PMID- 20350224 TI - Pigmented epithelioid melanocytoma: a recently described melanocytic tumour of low malignant potential. PMID- 20350225 TI - Melanotic schwannoma mimicking metastatic pigmented melanoma: a pitfall in cytological diagnosis. PMID- 20350226 TI - Xeroderma pigmentosa with basal cell carcinoma and coexistent multicentric neurofibroma on face. PMID- 20350227 TI - Cerebrospinal fluid cytology in a case of primary diffuse leptomeningeal and pineal melanocytic lesion, with histological confirmation. PMID- 20350228 TI - Composite phaeochromocytoma-ganglioneuroma, an uncommon entity: report of two cases. PMID- 20350229 TI - Undifferentiated pleomorphic sarcoma (so-called malignant fibrous histiocytoma) of the inferior vena cava with extension into the right atrium. PMID- 20350230 TI - Monotypic epithelioid angiomyolipoma of the liver with TFE3 expression. PMID- 20350231 TI - Osseous metaplasia in a traditional serrated adenoma of the rectosigmoid colon. PMID- 20350232 TI - Focal haemophagocytosis within an undifferentiated colon carcinoma: a potential for misdiagnosis. PMID- 20350233 TI - Bowel abscess with Nocardia veterana associated with colon carcinoma. PMID- 20350234 TI - Light chain deposition disease presenting as massive hepatomegaly. PMID- 20350235 TI - Haemoglobin Stanleyville II modifies sickle disease phenotype. PMID- 20350236 TI - Percutaneous laser photocoagulation of tumour vessels for the treatment of a rapidly growing sacrococcygeal teratoma in an extremely premature fetus. PMID- 20350237 TI - Gitelman syndrome-associated severe hypokalemia and hypomagnesemia: case report and review of the literature. AB - We report a case of a woman with Gitelman syndrome who presented to our hospital mainly due to hyperemesis. Following her admission, intravenous potassium and magnesium supplementation was commenced to counter the observed hypokalemia and hypomagnesemia. Hyperemesis receded and although serum potassium remained low, she became asymptomatic. Oral potassium and magnesium supplementation was administered throughout pregnancy and biweekly ion level measurements were scheduled. Despite the intensive replacement, ion levels remained constantly low. She delivered at 38 weeks with an elective caesarean section because of a breech presentation, a healthy female baby weighing 3350 g. Neonatal electrolyte profile was normal. PMID- 20350238 TI - Histologic chorioamnionitis and acute neurologic impairment in premature infants. AB - OBJECTIVE: To determine if histologic chorioamnionitis is associated with acute neurologic impairment as evaluated by auditory brainstem response in premature infants. METHODS: A prospective study was performed to compare auditory neural function at birth between premature infants with maternal histologic chorioamnionitis and infants without maternal histologic chorioamnionitis. Our inclusion criteria was 28-33 weeks gestational age (GA) infants who had maternal placental histopathology performed. Infants with toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex (TORCH) infections, chromosomal disorders, cranio-facial anomalies and/or unstable condition were excluded. Bilateral monaural auditory brainstem evoked responses were performed using 80 dB nHL click stimuli at a repetition rate of 29.9/s within 48 h after birth. RESULTS: Of 101 infants who met study criteria, 29 infants were born with history of maternal histologic chorioamnionitis. There were no significant differences between infants with histologic chorioamnionitis and infants without histologic chorioamnionitis in perinatal factors except for GA, pregnancy induced hypertension, and exposure to antenatal magnesium sulphate. After controlling for confounders, histologic chorioamnionitis was not associated with prolonged absolute wave latencies I, III, and V and/or decreased frequency of mature auditory waveform compared to infants without histologic chorioamnionitis. CONCLUSION: Histologic chorioamnionitis is not associated with neurologic impairment at birth in premature infants. PMID- 20350239 TI - Indomethacin as a diagnostic and therapeutic tool in the management of progressive cervical shortening diagnosed by trans-vaginal sonography. AB - OBJECTIVE: To evaluate the role of indomethacin in discriminating between preterm labour and cervical insufficiency-related cervical shortening. METHODS: Retrospective analysis of all cases of cervical shortening on singleton gestations. All patients were treated according to our protocol with one or more of the following three modalities: (1) bed rest only, (2) bed rest and indomethacin and (3) cervical cerclage, bed rest, and indomethacin. OUTCOMES: foetal loss <24 weeks, birth weight, delivery <34 weeks, and delivery <37 weeks. RESULTS: We treated 342 patients: 167 (48.8%) with bed rest only, 21 (6.1%) with cerclage, and 154 (45.1%) with indomethacin. By 28 weeks 56 (16.3%) remained stable or improved with bed rest only, 91 (26.6%) failed indomethacin and required cerclage, and the remaining 173 (50.6%) responded well to indomethacin and nifedipine. Birth weight was 3119 g +/- 651 (SD) and GA at delivery 37.4 weeks +/- 2.5 (SD). Of the 342 patients, 4 (1.2%) aborted <24 weeks, 1 was terminated (achondroplasia), 320 (93.6%) patients delivered >34 weeks and 301 (88.1%) >37 weeks. CONCLUSIONS: Use of indomethacin in patients with cervical shortening discriminates patients with cervical insufficiency from those in premature labour and improves outcomes in comparison to existing published reports. PMID- 20350240 TI - Manual rotation to reduce caesarean delivery in persistent occiput posterior or transverse position. AB - OBJECTIVE: To examine mode of delivery and perinatal outcomes in women with occiput posterior (OP) or transverse (OT) position in the second stage of labour with a trial of manual rotation compared to expectant management. METHODS: A retrospective cohort study was designed to examine mode of delivery and perinatal morbidity in women who underwent a trial of manual rotation (n = 731) compared to expectant management (n = 2527) during the second stage of labour with the fetus in OP/OT position. Chi-square test was used to compare categorical outcomes and multivariable logistic regression models were used to control for potential confounders. RESULTS: Compared to expectant management, women with manual rotation were less likely to have: caesarean delivery (CD) [adjusted odds ratio (aOR) 0.12; 95% confidence interval (CI) 0.09-0.16], severe perineal laceration [aOR 0.64; (0.47-0.88)], postpartum haemorrhage [aOR 0.75; (0.62-0.98)], and chorioamnionitis [aOR 0.68; (0.50-0.92)]. The number of rotations attempted to avert one CD was 4. In contrast, women who had a trial of rotation had an increased risk of cervical laceration [aOR 2.46; (1.1-5.4)]. CONCLUSIONS: Compared with expectant management, a trial of manual rotation with persistent fetal OP/OT position is associated with a reduction in CD and adverse maternal outcomes. PMID- 20350241 TI - A comparison of first trimester measurements for prediction of delivery date. AB - OBJECTIVE: We evaluated the biometric values of first trimester measurements for prediction of delivery date by computing new dating formulas and evaluating them within the same settings in a large population. METHODS: We studied unselected pregnancies undergoing first trimester ultrasound examination by a single experimented sonographer. We used 331 pregnancies conceived by assisted reproductive treatment to build a new dating formula and another 3667 normal pregnancies with spontaneous delivery to test the accuracy of these measurements and formulas. The reproducibility of the two measurements which performed best was done. RESULTS: Crown-rump length (CRL) had the lowest random and systematic errors. The mean (SD) of errors in predicting day of delivery were 0.023 (7.873), 0.092 (7.928), 0.088 (8.208) and 0.269 (8.310) for CRL, biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC) respectively. CRL and BPD proved to be highly reproducible. The percentages of deliveries within +/ 10 and +/-14 days of the predicted term were comparable for CRL and BPD but were significantly smaller when using HC, AC. CONCLUSIONS: Both CRL and BPD proved to be highly reproducible and able to predict with good precision the date of delivery. However, CRL has significantly lower random and systematic errors than all other biometric parameters. PMID- 20350242 TI - A novel 15bp micro-duplication in SF-1 gene showing diverse phenotypic spectrum in a Chinese family. AB - OBJECTIVE: To determine the genetic cause of sex reversal in a Chinese family. METHODS: Two sisters aged 21 and 20 years old were referred for primary amenorrhoea and poor secondary sexual development. They were subjected to clinical, endocrinologic and ultrasonographic investigation, and molecular analysis including cytogenetics, array CGH, SRY and SF-1 mutation screening. RESULTS: A novel 15bp micro-duplication in the SF-1 gene in patients affected by 46,XY sex-reversal phenotype without dysgenesis. CONCLUSION: The novel 15bp duplication of SF-1 gene affecting 46,XY females with diverse phenotypic spectrum. This provides new information for genetic counselling of disorders of sex development. PMID- 20350243 TI - Pattern and prenatal diagnosis of skeletal dysplasias in Qatar population. AB - OBJECTIVE: To determine the pattern of skeletal dysplasias in Qatar population and to assess the accuracy of prenatal diagnosis and prognosis. METHODS: This was a retrospective descriptive study of 30 women with high risk for skeletal dysplasias. The recruited women were submitted to clinical assessment, ultrasound scanning using 2-dimensional, 3-dimensional/4-dimensional and colour Doppler technique with possible molecular diagnosis. The findings were compared with the postnatal or postmortem assessments. Final diagnosis was based on clinical examination, skeletal survey, autopsy and molecular testing as deemed necessary. RESULTS: Thirty cases of skeletal dysplasia were antenatally diagnosed over 4 year period with family history in few cases. Among many entities thanatophoric dysplasia showed largest prevalence [7(23%)]. Prenatal diagnosis was accurate in 76% of foetuses while the first indicator of abnormality was a suspected anomaly found during routine ultrasound assessment in most cases [17(56%)]. Prediction of lethality based on ultrasound findings was 100% accurate. CONCLUSIONS: This study confirmed the possibility of good prenatal diagnosis of skeletal dysplasias present among Qatar population. Diagnosis based on ultrasound assessment will improve by adding molecular techniques with positive impact on prenatal care. PMID- 20350244 TI - Analysis of diagnostic confidence: application to data from a prospective randomized controlled trial of CT for acute abdominal pain. AB - BACKGROUND: Changes in diagnostic confidence are used as a measure of a test's efficacy. There are several methods for analyzing such data, but it is unclear which are most robust. PURPOSE: To compare analytical methods for assessing diagnostic confidence, applied to data from a prospective study of computed tomography (CT) for acute abdominal pain. MATERIAL AND METHODS: Changes in diagnostic confidence in an illustrative case study were evaluated using five methods: "Basic," "Retained diagnosis," "Omary," "Tsushima," and "Score-based." The case study was a randomized controlled trial of patients admitted to hospital for acute abdominal pain for whom immediate CT was not indicated, comparing "early" CT undertaken within 24 h of admission versus routine standard practice. Admitting surgeons recorded their diagnoses and confidences (5-point scale, 10 90%) both on admission and after 24 h. One- and two-sample t tests, and intention to-treat and as-treated analyzes, were performed using all five analytic methods. RESULTS: In the case study, 118 patients were randomized to early CT (n=55) or standard practice (n=63). Mean (SD) diagnostic confidence increased between the two time points by 20.7 (25.2)% and 13.0 (24.9)%, respectively. Early CT showed increases in diagnostic confidence by all one-sample analyzes (all P<0.055). Compared with standard practice, early CT showed significant increases in diagnostic confidence on an a) as-treated basis when using Basic, Omary and Score based analyzes (P<0.045), but not by the other two analytic methods, and b) intention-to-treat, only by Omary analysis. CONCLUSION: The method of analysis used to evaluate diagnostic confidence can influence conclusions about a test's efficacy. Methods incorporating the soundest analytical principles are recommended. PMID- 20350245 TI - Pulmonary CT findings in relapsing polychondritis. AB - BACKGROUND: Relapsing polychondritis (RPC) is a rare rheumatic disease characterized by recurrent inflammation of cartilaginous structures, with airway involvement a major cause of morbidity and mortality. PURPOSE: To retrospectively evaluate airway and lung abnormalities in RPC with computed tomography (CT). MATERIAL AND METHODS: From January 2004 to May 2009, 21 patients with RPC (12 men, 9 women; 13-65 years old) underwent chest CT examinations. Two chest radiologists evaluated the CT images retrospectively. Abnormal findings, including airway stenosis, airway malacia, air trapping, and airway wall thickening with or without calcifications, were observed and noted. RESULTS: Major abnormal CT findings were observed in eight patients (38.1%), which included airway wall thickening (n=7), airway stenosis (n=6), airway malacia (n=6), airway wall calcification (n=8), and air trapping (n=3). Mediastinal lymph nodes were found in 12 patients. Lung infection was identified in four patients and interstitial lung disease in six patients. CONCLUSION: The CT findings in patients with RPC consisted mainly of airway wall thickening, airway stenosis, airway malacia, airway wall calcification, and air trapping. PMID- 20350246 TI - MRI of the cat brain in the study of vascular permeability after intraarterial carotid injection of triolein. AB - BACKGROUND: Triolein emulsion embolization into the carotid artery depicts reversible increased vascular permeability that can promote the effect of chemotherapy or can reduce the amount of chemotherapeutic drugs for equivalent effectiveness. PURPOSE: To establish the minimum dosage of 0.5% triolein for studying vascular permeability changes in a triolein emulsion model. MATERIAL AND METHODS: Sixty-six cats were divided into six groups based on the amount of emulsified triolein (0.5%) infused into the carotid artery: group 1 (n=12, 6 ml/kg), group 2 (n=12, 4.5 ml/kg), group 3 (n=12, 3 ml/kg), group 4 (n=10, 1.5 ml/kg), group 5 (n=10, 1 ml/kg), and group 6 (n=10, 3 ml/kg of saline (control group)). T1-weighted, T2-weighted, and post-contrast T1-weighted MRI was performed 2 h after the infusion of the triolein emulsion. Contrast enhancement ratios (CERs) were obtained with pre- and post-contrast T1-weighted images in the ipsilateral and contralateral hemispheres. Signal intensity ratios (SIRs) of the ipsilateral and contralateral hemispheres were evaluated on T2-weighted images. After removal of the brain tissues, edema ratios in the ipsilateral and contralateral hemispheres were obtained from wet versus dry brain weights. Data were statistically evaluated by analysis of variance, followed by the Tukey honestly significant difference test to compare the difference in the mean CER of the ipsilateral and contralateral hemispheres, mean SIR on T2-weighted image, and mean edema ratio between each group when overall significance was attained. RESULTS: In the ipsilateral hemispheres, the difference in the CER between the control group and groups 1 (P=0.004), 2 (P=0.043), and 3 (P=0.008) were statistically significant. The difference in the CERs between the triolein emulsion groups was not statistically significant (P>0.05). The T2-weighted SIRs were significantly different between the control group and groups 1 (P=0.027) and 2 (P=0.004). However, the edema ratios of all doses in the triolein emulsion groups showed no significant differences compared with the control group. CONCLUSION: The minimum dosage of 0.5% triolein emulsion to achieve increased vascular permeability in the hemisphere in cat brains appears to be 3 ml/kg. This minimum dosage of triolein emulsion can be useful for acquiring basic data in further studies of vascular permeability changes in a triolein emulsion model. PMID- 20350247 TI - Probably benign breast lesions on ultrasonography: a retrospective review of ultrasonographic features and clinical factors affecting the BI-RADS categorization. AB - BACKGROUND: The retrospective review of probably benign lesions on mammograms is well investigated. Although suspicious malignant ultrasonography (US) features have been detected on retrospective reviews of US examinations, the review of probably benign lesions on US is rarely studied. PURPOSE: To investigate how many probably benign lesions on US fulfilled the published criteria and to evaluate how clinical and personal factors influenced the categorization of breast lesions. MATERIAL AND METHODS: A total of 920 nodules in 920 women with more than 24 months follow-up after the initial category 3 assessment on US or excision were included. We retrospectively reviewed the initial US images according to previously published criteria, and evaluated several factors that could influence the characterization of breast lesions in clinical practice such as age, multiplicity, palpability, radiologist's experience, and lesion size. RESULTS: Of 920 lesions, 906 (98.5%) were benign and 14 (1.5%) were malignant. Of 920 lesions, 376 (40.9%) including 13 malignancies were reassessed as category 4. If strict criteria had been applied at initial US examination, the positive biopsy rate would have been only 3.5% (13/376) and 96.5% (363 of 376) biopsies would have been unnecessary. Lesions in women 40 years or older and multiple lesions were more frequently reassessed as category 4 (P<0.00 and P=0.01, respectively). The presence of palpability, lesion size, and the radiologist's experience did not significantly influence the categorization of breast lesions on US. Of 920 probably benign lesions, 40.9% could be classified as category 4 lesions when strict criteria were applied in initial practice. CONCLUSION: The multiplicity of the lesion and the patient's age were found to have a significant influence on the classification of probably benign solid masses. PMID- 20350248 TI - Malignant renal cysts: diagnostic performance and strong predictors at MDCT. AB - BACKGROUND: Utilization of multidetector-row CT (MDCT) is anticipated to improve the diagnostic accuracy and reliability for determining malignant cysts. PURPOSE: To assess the diagnostic accuracy, interobserver agreement, benefit of consensus reading, and strong predictors of malignancy in determining malignant cystic renal masses at MDCT. MATERIAL AND METHODS: Two radiologists independently rated the probability of malignancy at MDCT in 72 benign and 53 malignant cysts. The accuracy and interobserver agreement for determining malignant cysts were evaluated. The strong predictors of malignancy were determined, and in patients with interobserver disagreement for determining malignant cysts, consensus readings were performed. RESULTS: Az value of the two readers was 0.905-0.936 and the sensitivity and specificity were 85-89% and 83-93%, respectively. The overall interobserver agreement for determining the malignant cyst was good as the kappa value was 0.696 (% agreement, 61% (76/125)). Thickened irregular wall, thickened irregular septa, and enhancing soft tissue component were strong predictors for malignancy with both readers. In the 17 patients with interobserver disagreement for determining malignant cysts, the sensitivity was improved from 38-63% to 89% by the consensus reading. CONCLUSION: At MDCT, some false negative decisions for determining malignant cysts can be corrected by consensus reading, and thickened irregular septa, thickened irregular wall, and enhancing soft tissue component are the strong predictors of malignant cysts. PMID- 20350249 TI - Differentiation between grade 3 and grade 4 articular cartilage defects of the knee: fat-suppressed proton density-weighted versus fat-suppressed three dimensional gradient-echo MRI. AB - BACKGROUND: Fat-suppressed (FS) proton density (PD)-weighted magnetic resonance imaging (MRI) and FS three-dimensional (3D) gradient-echo imaging such as spoiled gradient-recalled (SPGR) sequence have been established as accurate methods for detecting articular cartilage defects. PURPOSE: To retrospectively compare the diagnostic efficacy between FS PD-weighted and FS 3D gradient-echo MRI for differentiating between grade 3 and grade 4 cartilage defects of the knee with arthroscopy as the standard of reference. MATERIAL AND METHODS: Twenty-one patients who had grade 3 or 4 cartilage defects in medial femoral condyle at arthroscopy and knee MRI were included in this study: grade 3, >50% cartilage defects; grade 4, full thickness cartilage defects exposed to the bone. Sagittal FS PD-weighted MR images and FS 3D gradient-echo images with 1.5 T MR images were independently graded for the cartilage abnormalities of medial femoral condyle by two musculoskeletal radiologists. Statistical analysis was performed by Fisher's exact test. Inter-observer agreement in grading of cartilage was assessed using kappa coefficients. RESULTS: Arthroscopy revealed grade 3 defects in 17 patients and grade 4 defects in 4 patients in medial femoral condyles. For FS 3D gradient echo images grade 3 defects were graded as grade 3 (n=15) and grade 4 (n=2), and all grade 4 defects (n=4) were correctly graded. However, for FS PD-weighted MR images all grade 3 defects were misinterpreted as grade 1 (n=1) and grade 4 (n=16), whereas all grade 4 defects (n=4) were correctly graded. FS 3D gradient echo MRI could differentiate grade 3 from grade 4 defects (P=0.003), whereas FS PD-weighted imaging could not (P=1.0). Inter-observer agreement was substantial (kappa=0.70) for grading of cartilage using FS PD-weighted imaging, whereas it was moderate (kappa=0.46) using FS 3D gradient-echo imaging. CONCLUSION: FS 3D gradient-echo MRI is more helpful for differentiating between grade 3 and grade 4 cartilage defects than is FS PD-weighted imaging. PMID- 20350250 TI - Sick leave of spouses to cancer patients before and after diagnosis. AB - BACKGROUND: The impact of cancer on spouses of cancer patients may be considerable in many aspects. Our objective was to evaluate sick leave in spouses of cancer patients before and after the diagnosis. MATERIAL AND METHODS: Using Swedish population-based registries, we studied sick leave of spouses to patients with newly diagnosed colon, rectal, lung, prostate, or breast cancer. We identified the cancer patients via the Swedish Cancer Registry and obtained information of their spouse through linkage with the population register. We assessed the number of sick leave episodes and sick days one year before until one year after the spouses' cancer diagnosis by cross-referencing with Swedish Social Insurance Agency data. We also compared the number of sick days of spouses with the general population adjusted for age, sex and partner status. RESULTS: In general, spouses (N=1 923) to cancer patients had an increase in the frequency of new episodes of sick leave in the months before and after the cancer diagnosis. Spouses of lung cancer patients had most sick leave episodes, and the largest number of sick days per person. In comparison to the general population, spouses in the lung cancer group also had the highest standardised sick day ratio 1.76; 95% confidence interval 1.24, 2.40. The corresponding risk for spouses in other groups of cancer was not significantly increased. DISCUSSION: In Sweden there is often increased sick leave of spouses to cancer patients. It may be due to emotional stress and physical reactions that follow with cancer which needs to be further explored in order to provide adequate support and care. PMID- 20350251 TI - Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: results of the ATBC Study. AB - AIM: To determine whether alpha-tocopherol or beta-carotene supplementation affects diabetic macrovascular complications and total mortality. METHODS: This study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a double-blind, randomized trial with a 2x2 factorial design. A total of 29,133 middle-aged male smokers received either vitamin E 50 mg/day or beta-carotene 20 mg/day, or both, or placebo for a median of 6.1 years. At base line, 1700 men had type 2 diabetes. Of these men, 662 were diagnosed with first ever macrovascular complication, and 1142 died during the 19-year follow-up. RESULTS: Neither supplementation affected the risk of macrovascular complication or total mortality during the intervention period. For the alpha-tocopherol supplemented versus no alpha-tocopherol-supplemented, and beta-carotene supplemented versus no beta-carotene-supplemented we found relative risk (RR) 0.84 (95% confidence interval (CI) 0.65-1.10) and RR 1.15 (95% CI 0.89-1.50) for macrovascular complication, respectively, and RR 1.00 (95% CI 0.80-1.25) and RR 1.06 (95% CI 0.85-1.33) for total mortality, respectively. No essential changes were found in these effects when the follow-up was extended up to 19 years. CONCLUSION: Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers. PMID- 20350252 TI - Birthplace in area with high coronary heart disease mortality predicts the severity of coronary atherosclerosis among middle-aged Finnish men who had migrated to capital area: the Helsinki sudden death study. AB - BACKGROUND: Reasons why eastern-born male Finns have higher coronary heart disease (CHD) mortality than do western-born men are still unsettled. Recently, eastern birthplace was found to be an independent predictor of pre-hospital sudden cardiac death (SCD) in the new low-mortality area of residence. AIM: To investigate the association of birthplace with high CHD mortality attributes to more severe coronary atherosclerosis among men migrated to the low-mortality capital area. METHOD: Coronary atherosclerosis was measured in 373 western-born and 314 eastern-born out-of-hospital male deaths aged 33-70 years in Helsinki (The Helsinki Sudden Death Study), covering 24.6% of male deaths within this age group. CHD risk factors were obtained from an interview of a next of kin. RESULTS: In multivariate analysis there was a strong birthplace-by-age interaction with atherosclerosis (P = 0.0005). Eastern-born men <54 years had larger areas of fatty streaks (P = 0.0195), fibrotic plaque (P = 0.0133), calcification (P = 0.0009), total plaque area (P = 0.0011), and greater stenosis (P = 0.0004) in the left coronary compared to western-born men, independent of CHD risk factors. Amongst older men (>or=54 years) such an association no longer appeared. CONCLUSION: Higher CHD mortality among eastern-born men may be due to more severe coronary atherosclerosis independently of CHD risk factors, reflecting Finns' two-phase settlement history. PMID- 20350255 TI - Circadian clocks in mood-related behaviors. AB - The circadian clock organizes biochemical and physiological processes of an organism in a temporal fashion. This temporal organization is crucial to avoid interference of processes that have adverse effects on each other. Thus, disruption of temporal organization can lead to health problems and behavioral disorders related to mood alterations. To alleviate the consequences of a disrupted temporal organization in the body, it is of importance to understand the processes involved in the synchronization of all body clocks and their phase relationship to the environmental day/night cycle at the mechanistic level. This review will focus on internal and external factors affecting synchronization and function of the circadian system and highlight connections to mood-related behavior. PMID- 20350254 TI - Interleukin-18 gene polymorphism and markers of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study. AB - BACKGROUND AND AIM: Interleukin-18 (IL-18) is a pro-atherosclerotic cytokine. We wanted to evaluate whether IL-18 gene polymorphism associates independently of risk factors, with early subclinical markers of atherosclerosis (intima-media thickness (IMT), coronary artery compliance (CAC), and flow-mediated dilatation (FMD)) in a population of young healthy Caucasian adults. METHODS: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men). RESULTS: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the IL-18 gene. According to adjusted analysis of variance, the IL-18 gene polymorphism did not associate with subclinical atherosclerosis in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed. CONCLUSIONS: Among all study subjects, the polymorphism of the IL-18 gene is not associated with subclinical markers of atherosclerosis. However, among men one major IL-18 haplotype seemed to associate with substantially lower IMT values. PMID- 20350256 TI - The assessment of total cardiovascular risk in hypertensive subjects in primary care. AB - BACKGROUND: Recently published guidelines emphasize that detection of any subclinical target organ damage in hypertensive subjects should be regarded as a sign of high cardiovascular risk. AIM: To assess the ability of conventional multivariable cardiovascular disease risk prediction tools and high-sensitivity C reactive protein (hs-CRP) to identify hypertensive subjects with target organ damage. METHODS: Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), electrocardiographically determined left ventricular hypertrophy (ECG LVH), and base-line variables were measured in hypertensive subjects aged 45-70 years without established cardiovascular or renal disease or known diabetes. RESULTS: Of the 495 subjects, 123 (24.8% (95% CI 21.1-28.9)) had ABI <1.00, 81 (16.4% (95% CI 13.2-19.9)) had ECG-LVH, and 41 (8.3% (95% CI 6.0-11.1)) had eGFR <60 mL/min/1.73 m(2). In patients with SCORE <5% or Framingham risk <20%, any sign of target organ damage was found in 46% and 49% of patients, respectively. CONCLUSION: Assessment of ECG-LVH, ABI, and eGFR reclassifies a significant number of hypertensive patients to the high-risk category as compared to SCORE and Framingham risk prediction tools only. PMID- 20350257 TI - Characterization of colorectal tumors using narrow-band imaging magnification: combined diagnosis with both pit pattern and microvessel features. AB - OBJECTIVE: We aimed to clarify the clinical usefulness of narrow-band imaging (NBI) magnification for evaluating both pit appearances and microvessel architecture in comparison with evaluation of microvessel architecture alone in invasion depth of colorectal tumors. MATERIAL AND METHODS: A total of 189 colorectal lesions [37 adenomas, 73 intramucosal to scanty submucosal invasive carcinomas and 79 massive submucosal invasive (SM-m) carcinomas] were analyzed. All lesions showing irregular pit structure were observed by NBI magnifying endoscopy. Based on both pit appearance and microvessel features, lesions were classified into three grades (C1, C2, C3), as described previously. Also, lesions were classified as high or low by microvessel irregularity. Furthermore, the histopathological background and the inter- and intraobserver variability of C subtype were assessed. RESULTS: The SM-m rate of C1, C2 and C3 was 5.2, 60.5 and 92.7%, respectively. On the other hand, SM-m rate of lesion with mildly and highly irregular vessels was 13.3 and 55.0%, respectively. For the histopathological background, a high percentage of destruction of the glandular orifice, disappearance of the lamina muscularis mucosae and superficial exposure of desmoplastic reaction (DR) were observed in type C3. For C subtype classification of NBI magnification findings, the kappa value for interobserver variability was 0.749, and the kappa value for intraobserver variability was 0.745. CONCLUSIONS: NBI magnification findings evaluated by both pit appearances and microvessel features (C subtype) showing a good kappa value in variability are more useful in invasion depth diagnosis of colorectal tumor than those evaluated by microvessel features alone. PMID- 20350261 TI - An update on the immunopathogenesis of eosinophilic esophagitis. AB - Eosinophilic esophagitis (EoE) is a chronic clinicopathological entity characterized by large numbers of intraepithelial eosinophils infiltrating the esophageal mucosa, which is not caused by gastroesophageal reflux. This disease has become widely recognized over the past few years and new methods have been developed to reveal its underlying pathophysiological mechanisms. Owing to the high prevalence of food and/or airborne allergen sensitization in EoE patients, the allergic nature of the disease had to be defined, which has certain factors in common with other IgE-dependent entities, such as bronchial asthma or allergic rhinitis. Of these, some cytokines and chemokines previously studied in asthma have also been implicated in molecular mechanisms causing eosinophil-rich esophageal inflammation. However, the role played by IgE in relation to the esophageal eosinophilic infiltrate must be clarified, together with the possible function of mast cells in the inflammatory infiltrate and its activation stimuli. A putative role has also been recently suggested for gastroesophageal reflux in the origin of EoE that should be profoundly analyzed, together with the role of specific genes implicated in other digestive inflammatory disorders. This article reviews recent advances in the immunopathogenesis of EoE, which should also consider other pathways to activate the esophageal mucosal immune system. PMID- 20350258 TI - Possible gastrointestinal symptoms in a subset of children with autism. PMID- 20350253 TI - Impact of Xuezhikang on coronary events in hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). AB - BACKGROUND: The lowering of cholesterol concentrations in individuals at high risk for cardiovascular disease improves clinical outcome. Xuezhikang has a marked impact on lipids. METHODS: In this randomized, double-blinded, placebo controlled, parallel-group clinical trial, a total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (0.6 g twice daily, n = 1363) for an average of 4.5 years. The primary end-point was recurrent coronary events; the secondary end-point was all-cause mortality and other clinical events, including adverse effects. RESULTS: There were no differences between the Xuezhikang and placebo group in base-line characteristics. However, Xuezhikang treatment reduced the incidence of coronary events by 43.0% (P = 0.02), deaths from coronary heart disease (CHD) by 30.0% (P < 0.01), and all-cause mortality by 35.8% (P = 0.001). CONCLUSIONS: This study, for the first time, demonstrated that long-term Xuezhikang therapy resulted in significant reduction in cardiovascular events and death in Chinese hypertensive patients with previous MI in a safe manner. PMID- 20350260 TI - Disparities in organ allocation and access to liver transplantation in the USA. AB - Liver transplantation has become the standard of care for the treatment of chronic liver disease. In 1986, the United Network for Organ Sharing (UNOS) was formed to ensure the just and equitable allocation of donor livers. At the time, UNOS decided to use the Childs-Turcotte-Pugh scoring system to determine the degree of liver disease in potential transplant patients. Unfortunately, it was shown that the Childs-Turcotte-Pugh system was easily manipulated and did not provide equal access to donor organs. Owing to this fact, the Model of End Stage Liver Disease (MELD) score was instituted by UNOS in February 2002. While the institution of MELD has shown an improvement in organ allocation and outcomes, disparities still exist. This article discusses UNOS and the MELD allocation system as well as the racial, geographic and gender disparities that occur despite the institution of the MELD system. PMID- 20350263 TI - Advances in vaccination against Helicobacter pylori. AB - A vaccination against Helicobacter pylori may represent both prophylactic and therapeutic approaches to the control of H. pylori infection. Different protective H. pylori-derived antigens, such as urease, vacuolating cytotoxin A, cytotoxin-associated antigen, neutrophil-activating protein and others can be produced at low cost in prokaryote expression systems and most of these antigens have already been administered to humans and shown to be safe. The recent development by Graham et al. of the model of H. pylori challenge in humans, the recent published clinical trials and the last insight generated in animal models of H. pylori infection regarding the immune mechanisms leading to vaccine-induced Helicobacter clearance will facilitate the evaluation of immunogenicity and efficacy of H. pylori vaccine candidates in Phase II and III clinical trials. PMID- 20350262 TI - Population-based strategies for Helicobacter pylori-associated disease management: a Japanese perspective. AB - The prevalence of Helicobacter pylori infection is decreasing gradually in Japan mainly owing to an improvement in sanitary conditions. The guidelines for H. pylori management by the Japanese Society for Helicobacter Research, initially established in 2000 and revised in 2003, were revised dramatically in January 2009. The new guidelines accepted the use of new drugs and recommended trying the second-line eradication regimen. Moreover, the revised guidelines reflected the recent knowledge in Japan that metachronous gastric cancer prevalance is decreased significantly by the eradication of H. pylori infection. The Japanese Society for Helicobacter Research proposed that the cure of H. pylori infection should be presupposed to prevent gastric cancer from active gastritis universally developed in the infected subjects. Overall, the most important and dramatic revision is that all infected people are recommended to receive eradication therapy irrespective of the clinical outcomes in the Japanese population. PMID- 20350264 TI - What is the optimal therapy for Crohn's disease: step-up or top-down? AB - Crohn's disease (CD) is an idiopathic chronic inflammatory disorder of the digestive tract, which is incurable. Present therapeutic guidelines follow a sequential step-up approach that focuses on treating acute disease or 'inducing clinical remission' and subsequently aims to 'maintain clinical response'. In view of the chronic relapsing-remitting disabling disease course, new treatment approaches have been sought with the ultimate end point of disease course modification and mucosal healing. A recent preliminary study from D'Haens et al. has provided evidence suggesting that reversing the treatment paradigm from a 'step-up' to a 'top-down' approach may positively alter the natural course of this illness. Their findings indicate that early use of biologic therapy, in combination with immunomodulators, resulted in remission occuring more rapidly than the conventional 'step-up' treatment, with a longer time period to relapse, a decreased need for treatment with corticosteroids, a faster reduction in clinical symptoms, rapid decline in biochemical inflammatory markers (C-reactive protein) and improved endoscopic mucosal healing. These results, supported by previous studies on infliximab use, may hold a promising outcome of fewer stricturing complications, hospitalizations and surgeries for patients with CD. However, we need to better define the timing and candidates for the 'top-down' approach as we are still uncertain about the safety data and the long-term benefits if biologic agents are given as routine maintenance treatment, since most of the trials in CD have been short term, and approximately 30% of patients might have been overtreated. Future clinical trials will be crucial in answering these questions. PMID- 20350265 TI - Decision-making in ileocecal Crohn's disease management: surgery versus pharmacotherapy. AB - Ileocecal Crohn's disease (CD) can be treated medically as well as surgically. Both treatment modalities have been improved markedly in the last two decades, making CD more manageable. However, multidisciplinary research, addressing issues such as timing of surgery or medical treatment versus surgery, is scarce. Particularly in limited ileocecal CD, ileocolic resection might be a good alternative to long-term medical therapy. This review discusses the evidence on medical and surgical treatment options for ileocecal CD. It provides an aid in decision-making by discussing a treatment algorithm that can be used until further evidence on treatment is available. PMID- 20350266 TI - Does evidence exist to include dietary therapy in the treatment of Crohn's disease? AB - Prescription drugs and surgery are two common medical therapies for Crohn's disease (CD), an inflammatory bowel disease that affects the GI tract. Unfortunately, certain drugs can cause serious side effects, and surgeries must often be repeated. No diet has been established to alleviate the pain and suffering of CD patients. This is curious given the fact that a higher prevalence of food sensitivities exist in this population of patients, and enteral nutrition is not only the first-line of therapy in Japan, but a known research method used to place the majority of CD patients into remission. Although not all patients respond equally to diet, many simply remove symptom-provoking foods, such as dairy, wheat, corn and certain fruits and vegetables. We suggest assisting these patients in their self-assessment of irritating and symptom-provoking foods by educating them in the use of a food-symptom diary followed by a customized elimination diet trialed for 2-4 weeks to determine if there is any benefit to the individual patient. PMID- 20350267 TI - Metabolic and nutritional changes after bariatric surgery. AB - Bariatric surgery is the most durable intervention for severe obesity. Appropriate candidates for surgery include those with a body mass index over 40 kg/m(2), or those with a BMI over 35 kg/m(2) who also have weight-related comorbidities. Bariatric procedures are categorized as restrictive, where food intake is limited by a small gastric 'pouch'; malabsorptive, where the length of intestine available for nutrient absorption is decreased; or a combination of both. Although pure malabsorptive procedures, such as the now-historical jejunoileal bypass, achieve greater weight loss than restrictive procedures, they are generally associated with more postoperative metabolic problems. The Roux-en Y gastric bypass is currently considered the gold standard bariatric procedure for most patients. It results in excellent weight loss with minimal complications, but does require life-long vitamin supplementation. Compliance with vitamins and supplements is also mandatory after malabsorptive procedures. With these procedures, decreased oral intake, as well as altered absorption of nutrients from the GI tract, results in potentially low blood levels of a variety of micronutrients, especially iron, vitamin B12 and folate. Bariatric surgery also improves the comorbid conditions that are associated with obesity, such as diabetes, hypertension, dyslipidemia, obstructive sleep apnea, obesity hypoventilation, gastroesophageal reflux disease, asthma, venous stasis, polycystic ovary syndrome and pseudotumor cerebri. The resolution of diabetes is secondary to weight loss and may also be due to alteration of the enteroinsular axis. PMID- 20350268 TI - Biomarkers for drug-induced liver injury. AB - Of the estimated 10,000 documented human drugs, more than 1000 have been associated with drug-induced liver injury (DILI), although causality has not always been established clearly. Numerous biomarkers for DILI have been explored, but less than ten are adopted or qualified as valid by the US FDA. The biomarkers for DILI are individual or a panel of proteins, nucleic acids or metabolites from various sources, such as the liver, blood and urine. While most DILI biomarkers are drug independent, some possibly 'drug-specific' DILIs have been explored, but specificity and sensitivity of both types need to be improved for the diagnosis of DILI during drug development and in clinical practice. Novel approaches for DILI biomarkers have been actively investigated recently, but produced mainly animal-based biomarkers, which are possibly useful for drug development, but are not suitable or have not been validated for clinical applications. This review summarizes the current practice and future perspectives for DILI biomarkers. PMID- 20350269 TI - Endoscopic and laparoscopic treatment of gastroesophageal reflux. AB - Gastroesophageal reflux is extremely common in Western countries. For selected patients, there is an established role for the surgical treatment of reflux, and possibly an emerging role for endoscopic antireflux procedures. Randomized trials have compared medical versus surgical management, laparoscopic versus open surgery and partial versus total fundoplications. However, the evidence base for endoscopic procedures is limited to some small sham-controlled studies, and cohort studies with short-term follow-up. Laparoscopic fundoplication has been shown to be an effective antireflux operation. It facilitates quicker convalescence and is associated with fewer complications, but has a similar longer term outcome compared with open antireflux surgery. In most randomized trials, antireflux surgery achieves at least as good control of reflux as medical therapy, and these studies support a wider application of surgery for the treatment of moderate-to-severe reflux. Laparoscopic partial fundoplication is an effective surgical procedure with fewer side effects, and it may achieve high rates of patient satisfaction at late follow-up. Many of the early endoscopic antireflux procedures have failed to achieve effective reflux control, and they have been withdrawn from the market. Newer procedures have the potential to fashion a surgical fundoplication. However, at present there is insufficient evidence to establish the safety and efficacy of endoscopic procedures for the treatment of gastroesophageal reflux, and no endoscopic procedure has achieved equivalent reflux control to that achieved by surgical fundoplication. PMID- 20350271 TI - Occupational value and relationships to meaning and health: elaborations of the ValMO-model. AB - This study investigates the theoretical assumption of the Value and Meaning in Occupations model. The aim was to explore the relationship between occupational value, perceived meaning, and subjective health in a sample of individuals of working age, 50 men and 250 women. Frequency of experienced values in occupations was assessed through the Occupational Value instrument with pre-defined items. Perceived meaning was operationalized and assessed by the Sense of Coherence measure. Subjective health was estimated by two questions from the SF-36 questionnaire. The analyses implied descriptive analyses, correlations, and logistic regression analyses in which sociodemographic variables were included. The findings showed highly significant relationships between occupational value and perceived meaning and when belonging to the high group of occupational value the likelihood was tripled of belonging to the high group of perceived meaning. When married or cohabitating there was double the likelihood of belonging to the high group of perceived meaning. Although perceived meaning was found to be positively associated with subjective health, working full time was the most important factor in explaining subjective health, compared with working less than full time. The results confirm assumptions in the ValMO-model, and the importance of focusing on occupational value in clinical practice is highlighted. PMID- 20350272 TI - A prospective study of salvage high-intensity focused ultrasound for locally radiorecurrent prostate cancer: early results. AB - OBJECTIVE: After radical external beam radiation therapy (EBRT), local recurrence may benefit from definitive local therapy. The objective of this study was to evaluate the safety and short-term biochemical results and morbidity after salvage high-intensity focused ultrasound (HIFU) treatment in patients with biopsy-proven local prostate cancer recurrence after EBRT. MATERIAL AND METHODS: From October 2006 46 patients were treated with HIFU. Bone scan and abdominal CT/MRI scan were negative. Median follow-up was 9 months (range 3-24 months). RESULTS: The median prostate-specific antigen (PSA) nadir was 0.3 ng/ml (range 0 24 ng/ml). Eighteen patients (39.1%) were classified as failures. In addition, there were four patients (8.7%) with post-HIFU PSA nadir > 0.5 ng/ml. No patients died during follow-up. One patient developed urethrorectal fistulae and was successfully treated conservatively. Two patients developed urethrocutaneous fistulae. Seven patients (15.2%) and one patient (2.1%) developed grade 2 and grade 3 incontinence, respectively. Seven men (15.2%) had erectile function sufficient for intercourse pre-HIFU and only two men (4.3%) post-HIFU. CONCLUSIONS: Early results of salvage HIFU in patients with local recurrence of prostate cancer after radical EBRT indicate the procedure to be a reasonable treatment option, but better patient selection criteria are needed. The side effects are not negligible. PMID- 20350274 TI - Treatment of therapy related acute promyelocytic leukemia with the combination of all trans retinoic acid and arsenic trioxide without chemotherapy: a series of three patients. PMID- 20350273 TI - Vegetable and fruit intake and non-Hodgkin lymphoma survival in Connecticut women. AB - We investigated whether an increased intake of vegetables and fruits favors NHL survival. A cohort of 568 female cases of incident NHL diagnosed during 1996-2000 in Connecticut was followed up for a median of 7.7 years. Adjusted hazard ratios (HRs) were estimated by Cox proportional hazard models. Our results show that a pre-diagnostic high intake of vegetables appeared to favor overall survival (HR = 0.74, 95% CI 0.57-0.98) among patients with NHL who survived longer than 6 months. In particular, pre-diagnostic high intakes of green leafy vegetables and citrus fruits were associated with 29% (95% CI 0.51-0.98) and 27% (95% CI 0.54 0.99) reduced risk of death, respectively. When different types of vegetables and fruits were investigated separately, their impacts were found to vary in NHL subtypes. Our study suggests that increasing vegetable and citrus fruit consumption could be a useful strategy to improve survival in NHL patients. PMID- 20350275 TI - Infectious mononucleosis-like lesions, a rare manifestation of angioimmunoblastic T-cell lymphoma. PMID- 20350276 TI - Sequential monitoring of minimal residual disease in acute lymphoblastic leukemia: 7-year experience in a pediatric hematology/oncology unit. AB - We evaluated minimal residual disease (MRD) in 91 children with acute lymphoblastic leukemia (ALL) by PCR amplification of clonal rearrangements, immunoglobulin (IgH; VDJ rearrangement, CDR3 region) and T-cell receptor (TCRdelta). Sequential monitoring of MRD was performed at different time points during and after chemotherapy and was correlated to patient outcome. In total, 792 bone marrow samples were assessed for MRD at the end of induction, and during and after treatment completion. MRD positivity at the end of induction was detected in 12% of patients and was associated with high incidence of relapse, 54.55% (p = 0.0002), at 5 years. On the other hand, 88% of patients were MRD negative at the end of induction and the relapse rate at 5 years was very low, 5%. The frequency of MRD decreased to 16% in the first 6 months of chemotherapy; however, the incidence of relapse in MRD-positive patients remained high, 42.8%. After treatment completion (24-36 months from diagnosis), 32% patients were MRD positive and the relapse rate was 36.5% (p = 0.0009). Our results indicated that monitoring of MRD constituted an essential prognostic marker, and detection of MRD particularly at the end of induction and after treatment completion was strongly predictive for patient outcome. PMID- 20350277 TI - Gastrointestinal complications in children with acute myeloid leukemia. AB - Gastrointestinal complications in pediatric acute myeloid leukemia (AML) have not been systematically described in the literature. Our objective was to describe complications related to the small and large bowel in children with AML. Literature searches were conducted of Ovid Medline from 1950 to November 2009 and EMBASE from 1980 to November 2009. We included any study design that described gastrointestinal complications in children and/or adults with AML. Common gastrointestinal complications were typhlitis and enterocolitis. Less common complications included appendicitis, pneumatosis intestinalis, and perianal infections. Both leukemia infiltration and intensive chemotherapy likely play a role in the etiology of these conditions. There is a paucity of carefully conducted studies that describe the natural history of typhlitis and enterocolitis and evidence is needed to help guide the management of gastrointestinal complications. Gastrointestinal complications are relatively common in children with AML. Conduction of carefully performed cohort studies is needed to better understand the spectrum of symptoms and expected consequences of gastrointestinal complications. Randomized trials are required to develop evidence-based guidelines for the management of gastrointestinal complications in pediatric AML. PMID- 20350278 TI - Neutrophil function after bone marrow and hematopoietic stem cell transplant. AB - Bone marrow and hematopoietic stem cell transplants are life saving procedures for a variety of hematologic malignancies. Unfortunately, long-term survival is significantly impacted by the development of invasive fungal and bacterial infections, in part attributable to innate and adaptive immunologic defects post transplant. This review focuses specifically on neutrophil function after autologous and allogeneic bone marrow and hematopoietic stem cell transplant. PMID- 20350279 TI - Frail elderly patients with relapsed-refractory multiple myeloma: efficacy and toxicity profile of the combination of bortezomib, high-dose dexamethasone, and low-dose oral cyclophosphamide. PMID- 20350280 TI - The combination of thymosin and methylprednisolone for the treatment of a patient with colonic ulcers, subcutaneous nodules, and pleural effusion after dasatinib treatment for chronic myeloid leukemia. PMID- 20350281 TI - Therapeutic drug monitoring in highly active antiretroviral therapy. AB - IMPORTANCE OF THE FIELD: Despite the efficacy of combination antiretroviral therapy (ART), a large proportion of patients living with HIV/AIDS on ART does not achieve or maintain adequate virological suppression. Therapeutic drug monitoring (TDM) has been utilised to improve treatment outcomes of ART. AREAS COVERED IN THE REVIEW: The potential incorporation of TDM into the clinical HIV management is supported by the existing relationship between drug exposure and efficacy/toxicity, the high inter-patient variability pharmacokinetics, and the accurate, specific and rapid method for drug level determination. The current status of TDM in ART is reviewed in this article with discussions on its feasibility, potential use and limitations. WHAT THE READER WILL GAIN: Mounting evidence from clinical trials has indicated the potential use of TDM in reducing the rates of treatment failure and adverse effect, avoiding the drug interactions, and special populations, such as children, pregnant women and patients with co-infections. TDM may play an important role even in resource limited settings, to safeguard expanded use of bioequivalent generic antiretroviral drugs and avoid drug interactions with traditional Chinese medicines. TAKE HOME MESSAGE: TDM is still in the centre of controversy in that several critical issues need to be addressed, such as limited adherence assessment, inappropriate response predictors, insufficient validation of target concentration windows and lack of the quality control of assay. The utility of TDM will remain experimental until more data are obtained from large clinical trials showing the benefit of TDM. PMID- 20350282 TI - Vinorelbine for non-small cell lung cancer. AB - IMPORTANCE OF THE FIELD: Vinorelbine is a 'third-generation' vinca alkaloid approved for the treatment of NSCLC. The introduction of 'third-generation' drugs (vinorelbine, gemcitabine, taxanes) in platinum combination improved survival of patients with advanced NSCLC, with substantially similar results among the different drugs. Treatment toxicities are considerable in this setting. AREAS COVERED IN THIS REVIEW: This narrative review reports a synthesis of evidence available from published clinical trials, systematic reviews and meta-analyses on the activity and safety of vinorelbine, used as single agent or in combination chemotherapy in patients with NSCLC, from 1990 to 2009. WHAT THE READER WILL GAIN: When vinorelbine was administered in a weekly schedule without interruptions, the most common toxicity was neutropenia that often precluded administration of the drug, therefore, reducing the dose intensity. A schedule providing administration of vinorelbine on days 1 and 8 every 3 weeks seemed to improve the tolerability of the drug. Tolerability of the drug did not result lower in the elderly subset. None of the other 'third-generation' drugs were clearly better tolerated than vinorelbine. Moreover, in the adjuvant setting, vinorelbine is the only third-generation drug that demonstrated, in combination with cisplatin, a consistent improvement in survival on a long-term basis. TAKE HOME MESSAGE: Vinorelbine is an active and generally manageable therapeutic option for the treatment of both early and advanced NSCLC. PMID- 20350283 TI - Diabetes, hyperglycemia and accelerated atherosclerosis: evidence supporting a role for endoplasmic reticulum (ER) stress signaling. AB - Diabetes mellitus is associated with both micro- and macrovascular complications that can lead to significantly elevated incidence of retinopathy, nephropathy, neuropathy, myocardial infarction and stroke. The diabetic cardiovascular mortality rate exceeds 70% and individuals with diabetes are 2-3 times more likely to die from myocardial infarction and stroke than those with no history of diabetes even after controlling for other cardiovascular risk factors. Despite the profound clinical importance of vascular disease in patients with diabetes mellitus, our understanding of the molecular and cellular mechanisms by which diabetes promotes these vascular complications is incomplete. Endoplasmic reticulum (ER) stress and the unfolded protein response pathways have been previously associated with the development of several different diseases, including neurodegenerative disorders, cancer, and obesity. In addition, ER stress has been directly implicated in complications that are associated with diabetes, including pancreatic b cell dysfunction and insulin resistance. In this review we examine the potential role of endoplasmic reticulum stress in the initiation and progression of hyperglycemia-associated atherosclerosis. PMID- 20350284 TI - Evaluation of Vancoplus versus ceftriaxone against cephalosporin resistance MRSA strain in experimental meningitis model. AB - The aim of this study was to compare the efficacy of ceftriaxone plus vancomycin (Vancoplus) versus ceftriaxone alone against cephalosporin resistant methicillin resistant Staphylococcus aureus (MRSA) strain by using meningitis mice model. The MRSA strain ATCC 43300 was used to induce meningitis in mice. The mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 23 +/- 2 degrees C, humidity 65+/- 5% and with artificial fluorescent light 10-14 hrs. of light and dark, respectively. Twenty four mice were divided into four group containing six rats in each group. The ceftriaxone group received 28.57 mg/Kg body weight/day and the vancoplus group received 42.8 mg/Kg body weight/day and control as well as infected group received normal saline. The bacterial susceptibility test in CSF was performed for cephalosporin resistance MRSA strain by determining the lytic zone for the vancoplus and ceftriaxone antibiotic. The lytic zone was more in vancoplus as compared to ceftriaxone. It was also found that activities of antioxidant enzymes such as catalase were significantly increased (p<0.001) along with decreased (p<0.001) in lipid peroxidation (malonaldialdehyde) level in CSF of vancoplus treated group as compared to infected as well as ceftriaxone resistance group and come back to normal level. It was concluded that vancoplus beneficial for the patients who suffered from cephalosporin resistant MRSA bacterial strain. PMID- 20350285 TI - Discussion on pharmacogenetic interaction in G6PD deficiency and methods to identify potential hemolytic drugs. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common form of red blood cell enzymopathy. The disorder has reached polymorphic frequencies in different parts of the world due to the relative protection conferred against malaria. G6PD is a housekeeping X-linked gene encoding the first enzyme of the pentose phosphate pathway, an NADPH-producing dehydrogenase. Because erythrocytes do not generate NADPH in any other way than pentose phosphate pathway, they are more susceptible than any other cells to oxidative damages. G6PD deficiency is a prime example of a hemolytic anemia due to an interaction between an intracorpuscular cause and an extracorpuscular cause, because in the majority of cases an exogenous agent triggers hemolysis. Hemolysis, in fact, can be caused by exposure to oxidant agents. Although studies performed on epidemiology, genetics and molecular biology have broaden the information on G6pd deficiency, there are still no reliable and validated methods to test drug hemolytic potential in G6PD deficient patients. The review gives an overview of current knowledge on G6pd deficiency and on the methods that have been developed so far in order to identify drugs causing acute hemolytic anemia in G6pd deficiency. Moreover, we discuss the new potential preclinical strategies to assess, in vitro and in vivo, drug hemolytic risks. PMID- 20350286 TI - Paradoxical thrombotic effects of aspirin: experimental study on 1000 animals. AB - Aspirin administration decreases the risk of vascular ischemic problems. However, aspirin withdrawal may temporarily increase this risk. Previous studies reported that high dilutions of aspirin might cause a pro-thrombotic effect. This paper studies the effect of the lower end of the aspirin dose-response curve, its possible mechanism and clinical implications. PROTOCOL: Wistar rats were distributed into 100 groups of 10 rats each. Aspirin was injected at 100 mg/kg, 1 mg/kg and at several different aspirin dilutions along with cyclooxygenase (COX) 1 (SC-560), COX 2 (NS-398) or both selective inhibitors simultaneously using a laser-induced thrombosis model. RESULTS: The higher doses of aspirin decreased thrombosis. An opposite trend was observed with the lowest doses. SC-560 produced an anti-thrombotic effect antagonized by the highest aspirin dilutions. NS-398 created a pro-thrombotic effect that was antagonized by aspirin at higher doses. Simultaneous inhibition of COX 1 and 2 produced changes similar to COX 1 inhibition. CONCLUSION: COX 2 inhibition induced a pro-thrombotic effect that was antagonized by aspirin at 1 mg/kg or 100 mg/kg. The administration of the lowest aspirin doses induced a pro-thrombotic effect stronger than the antithrombotic effect of COX 1 selective inhibition. The mechanism of this last pro-thrombotic effect is induced by residual aspirin and is independent of COX 1 inhibition. This study may explain the cause of the paradoxical thrombo-embolic complications observed after aspirin discontinuation, an effect of residual aspirin rather than a rebound effect, and highlights the importance of low doses of substances as a barely studied source of side-effects. PMID- 20350287 TI - Bowel habit in preterm newborns: effect of new formulas. AB - Preterm infants may pass meconium only after the first 48 hours of life, even in absence of any gastrointestinal disease. The role of various factors in determining the time of meconium elimination has been recently assessed. Gestational age and start of feeding had been demonstrated to influence first meconium timing. The aim of our study was to evaluate time of first meconium passage and the time to achieve regular bowel movements (RBM), correlating these two events to different factors such as gestational age (GA), sex, type of delivery [caesarean section (CS) vs spontaneous delivery (SD)], 1' and 5' Apgar score (1'AS, 5'AS), time and type of feeding, oxygen requirement and any mode of respiratory support. PMID- 20350288 TI - WNT4 signaling in female gonadal development. AB - WNT4 signaling pathways represent an important step in the multi-faceted process of mammalian gonadal differentiation and the development of internal genitalia. WNT4 protein controls the cytoplasmatic stability of specific transcriptional coactivator beta catenin during both embriogenesis and adult homeostasis. The biological significance of WNT4 consists in determining the final female reproductive system, inhibiting Wolff ducts' differentiation, male steroidogenesis and vascular cell migration. An overview of WNT4 cellular mechanisms is given in order to understand its critical role in the genesis of various human diseases such as congenital malformations and gynecological disorders like polycystic ovary syndrome (PCOS). The final discussion focusses on several possible therapeutic uses of Wnt4 both during pregnancy in order to correct the genetic loss of function of the protein and during adulthood in order to normalize fertility in PCOS-affected females planning pregnancy. PMID- 20350289 TI - A broad variety of antigens contribute to the pathogenesis of atherosclerosis: how to neutralize noxious reactions in the host. AB - Atherosclerosis is an inflammatory disease characterized by lipid accumulation as well as vascular injury due to a massive infiltration of immune cells in the endothelial wall. Microbial and self- antigens are responsible for a persistent activation of immune and non-immune cells, thus leading to a condition of arterial chronic inflammation with plaque formation and rupture in complicated cases. In particular, the effects of bacteria, viruses and their toxic products as well as of glycated lipoproteins will be illustrated with special reference to the main inflammatory pathways triggered by a persistent antigenic load in the host. Taking into consideration this broad variety of antigens implicated in the pathogenesis of atherosclerosis, therapeutic approaches such as antibiotics, dietary intervention and immune therapies will be discussed. PMID- 20350290 TI - How close are we in achieving safe, affordable and reversible male contraceptives? AB - The world population, currently estimated to be over six billions, is expected to double in the next forty years. The projected growth will cause severe over crowding that will have an adverse effect on the ecological health of the planet. A recent survey by the United Nations found that a majority of men in many countries are willing to participate in family planning by taking full control of their fertility. However, the available contraceptives for men have either higher failure rates or they are irreversible. Thus, the contraceptive needs of tens of millions of men go unmet every day resulting in millions of unwanted pregnancies, and hundreds of thousands of abortions. Since the introduction of oral contraceptive (pill) for women over five decades ago, there have been numerous collaborative efforts by scientists and pharmaceutical companies to improve the effectiveness and delivery of contraceptives to women who wish to safely regulate their reproductive physiology. However, the contraceptive options available to men have not changed in several decades and are still limited to the use of condoms and timely withdrawal (coitus interruptus) or under going a minor surgical procedure (vasectomy) that prevents the release of spermatozoa during ejaculation. The first two methods have relatively higher typical-use failure rates, whereas the last approach is largely irreversible and not suitable for younger men. Despite non-stop efforts worldwide, we may still be several years away from providing safe, effective and affordable male contraceptives which will allow both men and women to participate fully in family planning. In this article, we will discuss various contraceptives currently available to regulate male fertility. In addition, we will summarize potentially new contraceptives for men that are at various stages of research and development. Finally, our intention is to discuss details of two safe, reversible and affordable male contraceptive approaches that are inching closure to being approved for use by the masses in India and China, the world's two most populous nations. PMID- 20350292 TI - Role of nuclear factor kappaB in liver health and disease. AB - NF-kappaB (nuclear factor kappaB) is a heterodimeric transcription factor that is constitutively expressed in all cell types and has a central role as a transcriptional regulator in response to cellular stress. In the present review, we discuss the role of NF-kappaB signalling in the maintenance of liver homoeostasis as well as in the pathogenesis of a wide variety of conditions affecting the liver, including viral hepatitis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Much of the current knowledge of NF-kappaB signalling in the liver relates to the canonical pathway, the IKK [IkappaB (inhibitor of kappaB) kinase] complex and the RelA subunit. We explore the weaknesses of the experimental approaches to date and suggest that further work is needed to investigate in detail the discreet functions of each of the Rel subunits in liver physiology and disease. PMID- 20350293 TI - T-cell-directed therapies in inflammatory bowel diseases. AB - Gut inflammation occurring in patients with IBDs (inflammatory bowel diseases) is associated with exaggerated and poorly controlled T-cell-mediated immune responses, which are directed against normal components of the gut flora. T-cells accumulate in the inflamed gut of IBD patients as a result of multiple mechanisms, including enhanced recruitment of cells from the bloodstream, sustained cell cycling and diminished susceptibility of cells to undergo apoptosis. Activated T-cells produce huge amounts of cytokines, which contribute to amplify and sustain the ongoing mucosal inflammation. Strategies aimed at interfering with T-cell accumulation and/or function in the gut have been employed with clinical success in patients with IBDs. In the present article, we review the available results showing that T-cell-directed therapies are useful to dampen the tissue-damaging immune response in IBDs. PMID- 20350291 TI - The substrates and binding partners of protein kinase Cepsilon. AB - The epsilon isoform of protein kinase C (PKCepsilon) has important roles in the function of the cardiac, immune and nervous systems. As a result of its diverse actions, PKCepsilon is the target of active drug-discovery programmes. A major research focus is to identify signalling cascades that include PKCepsilon and the substrates that PKCepsilon regulates. In the present review, we identify and discuss those proteins that have been conclusively shown to be direct substrates of PKCepsilon by the best currently available means. We will also describe binding partners that anchor PKCepsilon near its substrates. We review the consequences of substrate phosphorylation and discuss cellular mechanisms by which target specificity is achieved. We begin with a brief overview of the biology of PKCepsilon and methods for substrate identification, and proceed with a discussion of substrate categories to identify common themes that emerge and how these may be used to guide future studies. PMID- 20350294 TI - MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families. AB - BACKGROUND: Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. METHODS: Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene. RESULTS: We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4% (8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes. CONCLUSIONS: The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2. PMID- 20350295 TI - Variable-number tandem-repeat markers for typing Mycobacterium intracellulare strains isolated in humans. AB - BACKGROUND: Mycobacterium intracellulare, a species of the Mycobacterium avium complex, may be the cause of severe lung, lymphatic node, skin and bone/joint infections, as well as bacteriemia. The goal of this work was to identify Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU VNTR) markers and to study their variability in a collection of isolates of M. intracellulare collected in humans. We studied 61 isolates collected in humans between 2001 and 2008, as well as the reference strain, M. intracellulare ATCC 13950. RESULTS: We identified 45 MIRU-VNTR candidates, of which 17 corresponded to the MIRU-VNTR identified in the genome of M. intracellulare ATCC 13950. Among the 45 potential MIRU-VNTR, seven were selected for use in a MIRU-VNTR assay applied to our collection of isolates. Forty-four patterns were found by MIRU VNTR typing and the discriminatory power of the assay was high with a Hunter Gaston diversity index of 0.98. We do not have evidence of a particular distribution of MIRU-VNTR polymorphism according to clinical situation. CONCLUSIONS: Our results suggest that MIRU-VNTR typing could be used for molecular epidemiological studies applied to M. intracellulare. PMID- 20350297 TI - Antibacterial mono- and sesquiterpene esters of benzoic acids from Iranian propolis. AB - BACKGROUND: Propolis (bee glue) has been used as a remedy since ancient times. Propolis from unexplored regions attracts the attention of scientists in the search for new bioactive molecules. RESULTS: From Iranian propolis from the Isfahan province, five individual components were isolated: the prenylated coumarin suberosin 1, and four terpene esters: tschimgin (bornyl p hydroxybenzoate) 2, tschimganin (bornyl vanillate) 3, ferutinin (ferutinol p hydroxybenzoate) 4, and tefernin (ferutinol vanillate) 5. All of them were found for the first time in propolis. Compounds 2 - 5 demonstrated activity against Staphylococcus aureus. CONCLUSIONS: The results of the present study are consistent with the idea that propolis from unexplored regions is a promising source of biologically active compounds. PMID- 20350296 TI - The neuroepithelial basement membrane serves as a boundary and a substrate for neuron migration in the zebrafish hindbrain. AB - BACKGROUND: The facial branchiomotor neurons of cranial nerve VII undergo a stereotyped tangential migration in the zebrafish hindbrain that provides an ideal system for examining the complex interactions between neurons and their environment that result in directed migration. Several studies have shown the importance of the planar cell polarity pathway in facial branchiomotor neuron migration but the role of apical-basal polarity has not been determined. Here we examine the role of the PAR-aPKC complex in forming the basal structures that guide facial branchiomotor neurons on an appropriate migratory path. RESULTS: High resolution timelapse imaging reveals that facial branchiomotor neurons begin their migration by moving slowly ventrally and posteriorly with their centrosomes oriented medially and then, upon contact with the Laminin-containing basement membrane at the rhombomere 4-rhombomere 5 boundary, speed up and reorient their centrosomes on the anterior-posterior axis. Disruption of the PAR-aPKC complex members aPKClambda, aPKCzeta, and Pard6gb results in an ectopic ventral migration in which facial branchiomotor neurons escape from the hindbrain through holes in the Laminin-containing basement membrane. Mosaic analysis reveals that the requirement for aPKC is cell-nonautonomous, indicating that it is likely required in the surrounding polarized neuroepithelium rather than in facial motor neurons themselves. Ventral facial motor neuron ectopia can be phenocopied by mutation of lamininalpha1, suggesting that it is defects in maintenance of the laminin containing basement membrane that are the likely cause of ventral mismigration in aPKClambda+zeta double morphants. CONCLUSIONS: Our results suggest that the laminin-containing ventral basement membrane, dependent on the activity of the PAR-aPKC complex in the hindbrain neuroepithelium, is both a substrate for migration and a boundary that constrains facial branchiomotor neurons to the appropriate migratory path. PMID- 20350299 TI - Prognostic value of cell-free plasma DNA in patients with cardiac arrest outside the hospital: an observational cohort study. AB - INTRODUCTION: Many approaches have been examined to try to predict patient outcome after cardiopulmonary resuscitation. It has been shown that plasma DNA could predict mortality in critically ill patients but no data are available regarding its clinical value in patients after out-of-hospital cardiac arrest. In this study we investigated whether plasma DNA on arrival at the emergency room may be useful in predicting the outcome of these patients. METHODS: We performed a prospective study of out-of-hospital patients with cardiac arrest who achieved return of spontaneous circulation after successful resuscitation. Cardiovascular co-morbidities and resuscitation history were recorded according to the Utstein Style. The outcome measures were 24 h and overall in-hospital mortality. Cell free plasma DNA was measured by real-time quantitative PCR assay for the beta globin gene in blood samples drawn within two hours after the arrest. Descriptive statistics, multiple logistic regression analysis, and receiver operator characteristic (ROC) curves were calculated. RESULTS: Eighty-five consecutive patients were analyzed with a median time to return of spontaneous circulation of 27 minutes (interquartile range (IQR) 18 to 35). Thirty patients died within 24 h and 58 died during the hospital course. Plasma DNA concentrations at admission were higher in non-survivors at 24 h than in survivors (median 5,520 genome equivalents (GE)/ml, vs 2810 GE/ml, P < 0.01), and were also higher in patients who died in the hospital than in survivors to discharge (median 4,150 GE/ml vs 2,460 GE/ml, P < 0.01). Lactate clearance at six hours was significantly higher in 24 h survivors (P < 0.05). The area under the ROC curves for plasma DNA to predict 24-hour mortality and in-hospital mortality were 0.796 (95% confidence interval (CI) 0.701 to 0.890) and 0.652 (95% CI 0.533 to 0.770). The best cut-off value of plasma DNA for 24-h mortality was 4,340 GE/ml (sensitivity 76%, specificity 83%), and for in-hospital mortality was 3,485 GE/ml (sensitivity 63%, specificity 69%). Multiple logistic regression analysis showed that the risk of 24-h and of in-hospital mortality increased 1.75-fold and 1.36-fold respectively, for every 500 GE/ml increase in plasma DNA. CONCLUSIONS: Plasma DNA levels may be a useful biomarker in predicting outcome after out-of hospital cardiac arrest. PMID- 20350300 TI - Genetic population structure of sympatric and allopatric populations of Baltic ciscoes (Coregonus albula complex, Teleostei, Coregonidae). AB - BACKGROUND: Teleost fishes of the Coregonidae are good model systems for studying postglacial evolution, adaptive radiation and ecological speciation. Of particular interest is whether the repeated occurrence of sympatric species pairs results from in-situ divergence from a single lineage or from multiple invasions of one or more different lineages. Here, we analysed the genetic structure of Baltic ciscoes (Coregonus albula complex), examining 271 individuals from 8 lakes in northern Germany using 1244 polymorphic AFLP loci. Six lakes had only one population of C. albula while the remaining two lakes had C. albula as well as a sympatric species (C. lucinensis or C. fontanae). RESULTS: AFLP demonstrated a significant population structure (Bayesian thetaB = 0.22). Lower differentiation between allopatric (thetaB = 0.028) than sympatric (0.063-0.083) populations contradicts the hypothesis of a sympatric origin of taxa, and there was little evidence for stocking or ongoing hybridization. Genome scans found only three loci that appeared to be under selection in both sympatric population pairs, suggesting a low probability of similar mechanisms of ecological segregation. However, removal of all non-neutral loci decreased the genetic distance between sympatric pairs, suggesting recent adaptive divergence at a few loci. Sympatric pairs in the two lakes were genetically distinct from the six other C. albula populations, suggesting introgression from another lineage may have influenced these two lakes. This was supported by an analysis of isolation-by-distance, where the drift-gene flow equilibrium observed among allopatric populations was disrupted when the sympatric pairs were included. CONCLUSIONS: While the population genetic data alone can not unambiguously uncover the mode of speciation, our data indicate that multiple lineages may be responsible for the complex patterns typically observed in Coregonus. Relative differences within and among lakes raises the possibility that multiple lineages may be present in northern Germany, thus understanding the postglacial evolution and speciation in the C. albula complex requires a large-scale phylogenetic analysis of several potential founder lineages. PMID- 20350301 TI - Escherichia coli MW005: lambda Red-mediated recombineering and copy-number induction of oriV-equipped constructs in a single host. AB - BACKGROUND: Escherichia coli strain EL350 contains chromosomally integrated phage lambda Red recombinase genes enabling this strain to be used for modifying the sequence of resident clones via recombineering. BAC and fosmid clones are highly suitable for modification by recombineering but, because they are present at low (1-2) copies per cell, the DNA is difficult to isolate in high yield and purity. To overcome this limitation vectors, e.g. pCC1FOS, have been constructed that contain the additional replication origin, oriV, which permits copy-number to be induced transiently when propagated in a suitable host strain, e.g. EPI300, that supplies the cognate trans-replication protein TrfA. Previously, we used EL350 and EPI300 sequentially to recombineer oriV-equipped fosmid genomic clones and, subsequently, to induce copy-number of the resulting recombinant clone. To eliminate these intervening DNA isolation and transformation steps we retrofitted EL350 with a PBAD-driven trfA gene generating strain MW005 that supports, independently, both recombineering and copy-number induction. RESULTS: The PBAD driven copy of cre in EL350 was replaced seamlessly with a copy of trfA, PCR amplified from EPI300 chromosomal DNA, to generate MW005. This new strain has been used to both generate, via recombineering, a number of reporter gene fusions directly from pCC1FOS-based Caenorhabditis elegans genomic clones and to transiently induce copy-number of fosmid and BAC clones prior to DNA preparation. CONCLUSIONS: By retrofitting EL350, an established 'recombineering' E. coli strain, with a tightly regulated copy of trfA we have produced a new strain, MW005, which combines recombineering capacity with the useful ability to transiently induce copy-number of oriV-equipped clones. By coupling these two steps in a single strain, use of MW005 will enable the more rapid recombineering mediated production of recombinant clones in the yield and quality necessary for many downstream purposes. PMID- 20350302 TI - A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease. AB - INTRODUCTION: LY450139 (semagacestat) inhibits gamma-secretase, a key enzyme for generation of amyloid beta (Abeta), the peptide deposited in plaques in Alzheimer disease (AD). Previous data have shown that LY450139 lowers plasma Abeta, but has no clear effect on Abeta1-40 or Abeta1-42 levels in cerebrospinal fluid (CSF). By using targeted proteomics techniques, we recently identified several shorter Abeta isoforms, such as Abeta1-16, that in experimental settings increase during gamma-secretase inhibitor treatment, and thus may serve as sensitive biochemical indices of the treatment effect. Here, we test the hypothesis that these shorter Abeta isoforms may be biomarkers of gamma-secretase inhibitor treatment in clinical trials. METHODS: In a phase II clinical trial, 35 individuals with mild to moderate AD were randomized to placebo (n = 10) or LY450139 (100 mg (n = 15) or 140 mg (n = 10)) and underwent lumbar puncture at baseline and after 14 weeks of treatment. The CSF Abeta isoform pattern was analyzed with immunoprecipitation combined with MALDI-TOF mass spectrometry. RESULTS: The CSF levels of Abeta1-14, Abeta1-15, and Abeta1-16 showed a dose-dependent increase by 57% and 74%, 21% and 35%, and 30% and 67%, respectively in the 100-mg and 140-mg treatment groups. Abeta1-40 and Abeta1-42 were unaffected by treatment. CONCLUSIONS: CSF Abeta1-14, Abeta1-15, and Abeta1-16 increase during gamma-secretase inhibitor treatment in AD, even at doses that do not affect Abeta1-42 or Abeta1-40, probably because of increased substrate availability of the C99 APP stub (APP beta-CTF) induced by gamma-secretase inhibition. These Abeta isoforms may be novel sensitive biomarkers to monitor the biochemical effect in clinical trials. TRIAL REGISTRATION: Clinical Trials.gov NCT00244322. PMID- 20350303 TI - Origins of the amphiploid species Brassica napus L. investigated by chloroplast and nuclear molecular markers. AB - BACKGROUND: The amphiploid species Brassica napus (oilseed rape, Canola) is a globally important oil crop yielding food, biofuels and industrial compounds such as lubricants and surfactants. Identification of the likely ancestors of each of the two genomes (designated A and C) found in B. napus would facilitate incorporation of novel alleles from the wider Brassica genepool in oilseed rape crop genetic improvement programmes. Knowledge of the closest extant relatives of the genotypes involved in the initial formation of B. napus would also allow further investigation of the genetic factors required for the formation of a stable amphiploid and permit the more efficient creation of fully fertile re synthesised B. napus. We have used a combination of chloroplast and nuclear genetic markers to investigate the closest extant relatives of the original maternal progenitors of B. napus. This was based on a comprehensive sampling of the relevant genepools, including 83 accessions of A genome B. rapa L. (both wild and cultivated types), 94 accessions of B. napus and 181 accessions of C genome wild and cultivated B. oleracea L. and related species. RESULTS: Three chloroplast haplotypes occurred in B. napus. The most prevalent haplotype (found in 79% of accessions) was not present within the C genome accessions but was found at low frequencies in B. rapa. Chloroplast haplotypes characteristic of B. napus were found in a small number of wild and weedy B. rapa populations, and also in two accessions of cultivated B. rapa 'brocoletto'. Whilst introgression of the B. napus chloroplast type in the wild and weedy B. rapa populations has been proposed by other studies, the presence of this haplotype within the two brocoletto accessions is unexplained. CONCLUSIONS: The distribution of chloroplast haplotypes eliminate any of the C genome species as being the maternal ancestor of the majority of the B. napus accessions. The presence of multiple chloroplast haplotypes in B. napus and B. rapa accessions was not correlated with nuclear genetic diversity as determined by AFLPs, indicating that such accessions do not represent recent hybrids. Whilst some chloroplast diversity observed within B. napus can be explained by introgression from inter specific crosses made during crop improvement programmes, there is evidence that the original hybridisation event resulting in to B. napus occurred on more than one occasion, and involved different maternal genotypes. PMID- 20350304 TI - Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: new modeling and the role of high pKa values. AB - BACKGROUND: Unconjugated bilirubin (UCB) is an unstable substance with very low aqueous solubility. Its aqueous pKa values affect many of its interactions, particularly their pH-dependence. A companion paper shows that only our prior solvent partition studies, leading to pKa values of 8.12 and 8.44, met all essential requirements for valid pKa determinations. Other published values, generally lower, some below 5.0, were shown to be invalid. The present work was designed to derive suitable models for interpreting published data on the pH dependent binding of UCB with four agents, mentioned below, chosen because they are not, themselves, sensitive to changes in the pH range 4-10, and the data, mainly spectrometric, were of reasonable quality. RESULTS: These analyses indicated that the high pKa values, dianion dimerization constant and solubilities of UCB at various pH values, derived from our partition studies, along with literature-derived pH- and time-dependent supersaturation effects, were essential for constructing useful models that showed good qualitative, and sometimes quantitative, fits with the data. In contrast, published pKa values below 5.0 were highly incompatible with the data for all systems considered. The primary species of bound UCB in our models were: undissociated diacid for phosphatidylcholine, dianion for dodecyl maltoside micelles and cyclodextrins, and both monoanions and dianion for sodium taurocholate. The resulting binding versus pH profiles differed strikingly from each other. CONCLUSIONS: The insights derived from these analyses should be helpful to explore and interpret UCB binding to more complex, pH-sensitive, physiological moieties, such as proteins or membranes, in order to understand its functions. PMID- 20350305 TI - Review: Bilirubin pKa studies: new models and theories indicate high pKa values in water, dimethylformamide and DMSO. AB - BACKGROUND: Correct aqueous pKa values of unconjugated bilirubin (UCB), a poorly soluble, unstable substance, are essential for understanding its functions. Our prior solvent partition studies, of unlabeled and [14C] UCB, indicated pKa values above 8.0. These high values were attributed to effects of internal H-bonding in UCB. Many earlier and subsequent studies have reported lower pKa values, some even below 5.0, which are often used to describe the behavior of UCB. We here review 18 published studies that assessed aqueous pKa values of UCB, critically evaluating their methodologies in relation to essential preconditions for valid pKa measurements (short-duration experiments with purified UCB below saturation and accounting for self-association of UCB). RESULTS: These re-assessments identified major deficiencies that invalidate the results of all but our partition studies. New theoretical modeling of UCB titrations shows remarkable, unexpected effects of self-association, yielding falsely low pKa estimates, and provides some rationalization of the titration anomalies. The titration behavior reported for a soluble thioether conjugate of UCB at high aqueous concentrations is shown to be highly anomalous. Theoretical re-interpretations of data in DMSO and dimethylformamide show that those indirectly-derived aqueous pKa values are unacceptable, and indicate new, high average pKa values for UCB in non-aqueous media (>11 in DMSO and, probably, >10 in dimethylformamide). CONCLUSIONS: No reliable aqueous pKa values of UCB are available for comparison with our partition-derived results. A companion paper shows that only the high pKa values can explain the pH-dependence of UCB binding to phospholipids, cyclodextrins, and alkyl-glycoside and bile salt micelles. PMID- 20350306 TI - Bacterial diversity at different stages of the composting process. AB - BACKGROUND: Composting is an aerobic microbiological process that is facilitated by bacteria and fungi. Composting is also a method to produce fertilizer or soil conditioner. Tightened EU legislation now requires treatment of the continuously growing quantities of organic municipal waste before final disposal. However, some full-scale composting plants experience difficulties with the efficiency of biowaste degradation and with the emission of noxious odours. In this study we examine the bacterial species richness and community structure of an optimally working pilot-scale compost plant, as well as a full-scale composting plant experiencing typical problems. Bacterial species composition was determined by isolating total DNA followed by amplifying and sequencing the gene encoding the 16S ribosomal RNA. RESULTS: Over 1500 almost full-length 16S rRNA gene sequences were analysed and of these, over 500 were present only as singletons. Most of the sequences observed in either one or both of the composting processes studied here were similar to the bacterial species reported earlier in composts, including bacteria from the phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Deinococcus-Thermus. In addition, a number of previously undetected bacterial phylotypes were observed. Statistical calculations estimated a total bacterial diversity of over 2000 different phylotypes in the studied composts. CONCLUSIONS: Interestingly, locally enriched or evolved bacterial variants of familiar compost species were observed in both composts. A detailed comparison of the bacterial diversity revealed a large difference in composts at the species and strain level from the different composting plants. However, at the genus level, the difference was much smaller and illustrated a delay of the composting process in the full scale, sub-optimally performing plants. PMID- 20350307 TI - Mycobacterium avium subsp. paratuberculosis as a trigger of type-1 diabetes: destination Sardinia, or beyond? AB - Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease in which the insulin producing beta cell population is destroyed by the infiltrated T lymphocytes. Even though the exact cause of T1DM is yet to be ascertained, varying degree of genetic susceptibility and environmental factors have been linked to the disease progress and outcome. Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate zoonotic pathogen that causes chronic infection of intestines in ruminants, the Johne's disease. MAP that can even survive pasteurization and chlorination has also been implicated to cause similar type of enteritis in humans called Crohn's disease. With the increasing recognition of the link between MAP and Crohn's disease, it has been postulated that MAP is an occult antigen which besides Crohn's could as well be thought to trigger T1DM. Epitope homologies between mycobacterial proteins (Hsp 65) and pancreatic glutamic acid decarboxylase (GAD 65) and infant nutrition studies implicate MAP as one of the triggers for T1DM. PCR and ELISA analyses in diabetic patients from Sardinia suggest that MAP acts as a possible trigger for T1DM. Systematic mechanistic insights are needed to prove this link. Unfortunately, no easy animal model(s) or in-vitro systems are available to decipher the complex immunological network that is triggered in MAP infection leading to T1DM. PMID- 20350308 TI - Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags. AB - BACKGROUND: The Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genus Bungarus have been well characterized, a detailed compositional analysis of B. flaviceps is currently lacking. RESULTS: Here, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of a B. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of beta-bungarotoxin), phospholipase A2 (including chain A of beta-bungarotoxin), natriuretic peptide (NP), CRISPs, and C-type lectin. CONCLUSION: The 3FTxs were found to be the major component of the venom (39%). We found eight groups of unique 3FTxs and most of them were different from the well-characterized 3FTxs. We found three groups of Kunitz-type serine protease inhibitors (SPIs); one group was comparable to the classical SPIs and the other two groups to chain B of beta-bungarotoxins (with or without the extra cysteine) based on sequence identity. The latter group may be functional equivalents of dendrotoxins in Bungarus venoms. The natriuretic peptide (NP) found is the first NP for any Asian elapid, and distantly related to Australian elapid NPs. Our study identifies several unique toxins in B. flaviceps venom, which may help in understanding the evolution of venom toxins and the pathophysiological symptoms induced after envenomation. PMID- 20350309 TI - Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection. AB - BACKGROUND: In the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging. METHODS: Thirty seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method. RESULTS: MaR determined with T2-weighted imaging (34 +/- 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 +/- 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 +/- 12%. Myocardial salvage determined with T2-weighted imaging (58 +/- 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 +/- 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction. CONCLUSIONS: This study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial infarction. PMID- 20350310 TI - Bioprosthetic mitral valve thrombosis less than one year after replacement and an ablative MAZE procedure: a case report. AB - Occurrence of bioprosthetic valve thrombosis less than a year after replacement is very uncommon. Here, we describe a case of a 57 year old male, who presented 10 months after receiving a bioprosthetic mitral valve replacement with a two week history of dyspnea on exertion, worsening orthopnea and decreased exercise tolerance. Echocardiography revealed severe mitral regurgitation (MR), thrombosis of the posterior mitral leaflet, left atrial (LA) mural thrombus and a depressed left ventricular ejection fraction of twenty-five percent. Given severe clot burden and decompensated heart failure (New York Heart Association - NYHA class III) repeat sternotomy was done to replace the bioprosthetic mitral valve and remove LA mural thrombus. MR was resolved postoperatively. This brief report further reviews promoting factors, established guidelines and management strategies of bioprosthetic valve thrombosis. PMID- 20350311 TI - Early atherosclerosis and cardiac autonomic responses to mental stress: a population-based study of the moderating influence of impaired endothelial function. AB - BACKGROUND: Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis. METHODS: Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks. RESULTS: We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found. CONCLUSIONS: Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect. PMID- 20350312 TI - Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya. AB - BACKGROUND: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. METHODS: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. RESULTS: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). CONCLUSIONS: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients. PMID- 20350313 TI - The detection, treatment, and biology of epithelial ovarian cancer. AB - Ovarian cancer is particularly insidious in nature. Its ability to go undetected until late stages coupled with its non-descript signs and symptoms make it the seventh leading cause of cancer related deaths in women. Additionally, the lack of sensitive diagnostic tools and resistance to widely accepted chemotherapy regimens make ovarian cancer devastating to patients and families and frustrating to medical practitioners and researchers. Here, we provide an in-depth review of the theories describing the origin of ovarian cancer, molecular factors that influence its growth and development, and standard methods for detection and treatment. Special emphasis is focused on interactions between ovarian tumors and the innate and adaptive immune system and attempts that are currently underway to devise novel immunotherapeutic approaches for the treatment of ovarian tumors. PMID- 20350314 TI - Proteome analysis of soybean leaves, hypocotyls and roots under salt stress. AB - BACKGROUND: Salinity is one of the most widespread agricultural problems in arid and semi-arid regions that makes fields unproductive, and soil salinization is a serious problem in the entire world. To determine the effects of salt stress on soybean seedlings, a proteomic technique was used. RESULTS: Soybean plants were exposed to 0, 20, 40, or 80 mM NaCl for one week. The effect of treatment at 20 mM NaCl on plant growth was not severe, at 80 mM NaCl was lethal, and at 40 mM NaCl was significant but not lethal. Based on these results, proteins were extracted from the leaves, hypocotyls and roots of soybean treated with 40 mM NaCl. Nineteen, 22 and 14 proteins out of 340, 330 and 235 proteins in the leaves, hypocotyls and roots, respectively, were up- and down-regulated by NaCl treatment. In leaves, hypocotyls and roots, metabolism related proteins were mainly down-regulated with NaCl treatment. Glyceraldehyde-3-phosphate dehydrogenase was down-regulated in the leaf/hypocotyls, and fructokinase 2 was down-regulated in the hypocotyls/root with NaCl treatment. Stem 31 kDa glycoprotein precursor was up-regulated in all three organs with NaCl treatment. Glyceraldehyde-3-phosphate dehydrogenase was specifically down-regulated at the RNA and protein levels by salt stress. CONCLUSION: These results suggest that metabolism related proteins play a role in each organ in the adaptation to saline conditions. PMID- 20350315 TI - Multifactorial control and treatment intensity of type-2 diabetes in primary care settings in Catalonia. AB - BACKGROUND: Many studies on diabetes have demonstrated that an intensive control of glycaemia and the main associated risk factors (hypertension, dislipidaemia, obesity and smoking) reduce cardiovascular morbi-mortality. Different scientific societies have proposed a multifactorial approach to type 2 diabetes.The objective of this study was to identify the degree of control of glycosylated haemoglobin (HbA1c) and of cardiovascular risk factors in type 2 diabetic patients, using the GedapS 2004 guidelines, and to analyse the type and intensity of drug treatment. METHODS: This cross-sectional, multicentre, epidemiological study was conducted in a primary care setting in Valles Occidental South, Catalonia. Data were collected of 393 patients aged 18 and above who were diagnosed with diabetes mellitus type 2. Biodemographic and clinical data, cardiovascular risk factors, associated cardiovascular disease, and treatment were assessed. Descriptive and multivariable analysis with logistic regression was realized. RESULTS: A total of 392 patients with a mean age of 66.8 years (SD = 10.6) (45.4% male patients) were analyzed. The duration of diabetes was 8.4 years (SD = 7.6). The degree of multifactorial control of risk factors was only 2.6%, although in more than 50% individual cardiovascular risk factor was controlled, except for LDL cholesterol (40.6%) and systolic blood pressure (29.6%). Furthermore, only 13.0% of subjects had an optimal BMI, 27.5% an optimal waist circumference. Treatment for diabetes was prescribed in 82.7% of patients, for hypertension 70.7%, for dyslipidaemia 47.2% and 40.1% were taking antiplatelets. CONCLUSION: Over 50% of type 2 diabetic patients presented optimal control of the majority of individual cardiovascular risk factors, although the degree of multifactorial control of diabetes was insufficient (2.6%) and should be improved. Drug treatment can be intensified using a larger number of combinations, particularly in patients with target organ damage and associated clinical cardiovascular disease. PMID- 20350316 TI - Self efficacy for fruit, vegetable and water intakes: Expanded and abbreviated scales from item response modeling analyses. AB - OBJECTIVE: To improve an existing measure of fruit and vegetable intake self efficacy by including items that varied on levels of difficulty, and testing a corresponding measure of water intake self efficacy. DESIGN: Cross sectional assessment. Items were modified to have easy, moderate and difficult levels of self efficacy. Classical test theory and item response modeling were applied. SETTING: One middle school at each of seven participating sites (Houston TX, Irvine CA, Philadelphia PA, Pittsburg PA, Portland OR, rural NC, and San Antonio TX). SUBJECTS: 714 6th grade students. RESULTS: Adding items to reflect level (low, medium, high) of self efficacy for fruit and vegetable intake achieved scale reliability and validity comparable to existing scales, but the distribution of items across the latent variable did not improve. Selecting items from among clusters of items at similar levels of difficulty along the latent variable resulted in an abbreviated scale with psychometric characteristics comparable to the full scale, except for reliability. CONCLUSIONS: The abbreviated scale can reduce participant burden. Additional research is necessary to generate items that better distribute across the latent variable. Additional items may need to tap confidence in overcoming more diverse barriers to dietary intake. PMID- 20350317 TI - Peer substance use overestimation among French university students: a cross sectional survey. AB - BACKGROUND: Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use. METHODS: 12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use. RESULTS: Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline. CONCLUSIONS: Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses. PMID- 20350318 TI - Comparison of serum apolipoprotein A-I between Chinese multiple sclerosis and other related autoimmune disease. AB - BACKGROUND: Serum apolipoprotein (apo) A-I was considered to be an immune regulator and could suppress pro-inflammatory cytokines generated by activated T cell in some autoimmune diseases. However, the change of serum apoA-I levels in multiple sclerosis (MS) patients is unknown. METHODS: In the presentation we performed a study on serum apoA-I levels in the patients with MS. We enrolled some age and gender matched patients with MS, autoimmune demyelinating diseases (Guillain-Barre Syndrome and Clinically Isolated Syndrome), neuroinflammatory diseases (viral encephalitis), autoimmune connective diseases (rheumatoid arthritis and systemic lupus erythematosus) and healthy control groups, and tested their serum lipids levels: total cholesterol (TC), triglyceride (TG), high density lipoproteins (HDL), apolipoproteinB100 (apoB100), apolipoproteinA-I (apoA I). RESULTS: For all patients, age had no effect on serum apoA-I levels (P > 0.05). Meanwhile, we proved the highest serum apoA-I levels in MS patients and the lowest serum apoA-I levels in SLE patients. Serum apoA-I levels was significantly elevated in female MS patients (P = 0.033; P < 0.05). CONCLUSION: In short we believed that patients with MS and other autoimmune demyelination had significantly decreased serum levels of apo A-I. PMID- 20350319 TI - Cytogenetic contribution to uniparental disomy (UPD). AB - Uniparental disomy (UPD) is often considered as an event to be characterized exclusively by molecular genetic or epigenetic approaches. This review shows that at least one third of UPD cases emerge in connection with or due to a chromosomal rearrangement. Thus, additional (molecular) cytogenetic characterization of UPD cases is essential. Up to now > 1,100 UPD cases detected in clinical, non-tumor cases are reported in the literature. Recently, these cases were summarized in a regularly updated, freely available online database http://www.med.uni jena.de/fish/sSMC/00START-UPD.htm. Based of this, here the presently known imprinting syndromes, the chromosomal contribution to UPD phenomenon, and the cytogenetic subgroups of UPD, including cases with normal, abnormal balanced or unbalanced karyotype (like e.g. small supernumerary marker chromosomes and Robertsonian translocations) and segmental UPD are reviewed. Furthermore, chromosome fragmentation as a possible mechanism of trisomic rescue is discussed, which might help to explain the observed 1:9 rate of maternal versus paternal UPD present in cases with original trisomic karyotypes. Overall, as UPD is more but an interesting rarity, the genetic background of each "UPD-patient" needs to be characterized besides by molecular methods, also by molecular cytogenetics in detail. PMID- 20350320 TI - Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology. AB - BACKGROUND: Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV1) (criterion validity) and change of %FEV1 (responsiveness) during treatment in pediatric patients with acute asthma exacerbations. METHODS: We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV1, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests. RESULTS: We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV1 demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001). CONCLUSIONS: PEP demonstrates criterion validity and responsiveness in correlations with %FEV1. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus. PMID- 20350321 TI - Distinct genotypic profiles of the two major clades of Mycobacterium africanum. AB - BACKGROUND: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis (TB) and a member of the M. tuberculosis complex (MTC). Additional MTC species that cause TB in humans and other mammals include Mycobacterium africanum and Mycobacterium bovis. One result of studies interrogating recently identified MTC phylogenetic markers has been the recognition of at least two distinct lineages of M. africanum, known as West African-1 and West African-2. METHODS: We screened a blinded non-random set of MTC strains isolated from TB patients in Ghana (n = 47) for known chromosomal region-of-difference (RD) loci and single nucleotide polymorphisms (SNPs). A MTC PCR-typing panel, single-target standard PCR, multi-primer PCR, PCR-restriction fragment analysis, and sequence analysis of amplified products were among the methods utilized for the comparative evaluation of targets and identification systems. The MTC distributions of novel SNPs were characterized in the both the Ghana collection and two other diverse collections of MTC strains (n = 175 in total). RESULTS: The utility of various polymorphisms as species-, lineage-, and sublineage-defining phylogenetic markers for M. africanum was determined. Novel SNPs were also identified and found to be specific to either M. africanum West African-1 (Rv1332(523); n = 32) or M. africanum West African-2 (nat(751); n = 27). In the final analysis, a strain identification approach that combined multi-primer PCR targeting of the RD loci RD9, RD10, and RD702 was the most simple, straight forward, and definitive means of distinguishing the two clades of M. africanum from one another and from other MTC species. CONCLUSION: With this study, we have organized a series of consistent phylogenetically-relevant markers for each of the distinct MTC lineages that share the M. africanum designation. A differential distribution of each M. africanum clade in Western Africa is described. PMID- 20350323 TI - Cell and gene therapies: moving from research to clinic. PMID- 20350322 TI - Rationale and design: telephone-delivered behavioral skills interventions for Blacks with Type 2 diabetes. AB - BACKGROUND: African Americans with Type 2 diabetes (T2DM) have higher prevalence of diabetes, poorer metabolic control, and greater risk for complications and death compared to American Whites. Poor outcomes in African Americans with T2DM can be attributed to patient, provider, and health systems level factors. Provider and health system factors account for <10% of variance in major diabetes outcomes including hemoglobin A1c (HbA1c), lipid control, and resource use. Key differences appear to be at the patient level. Of the patient level factors, consistent differences between African Americans and American Whites with T2DM have been found in diabetes knowledge, self-management skills, empowerment, and perceived control. A variety of interventions to improve diabetes self-management have been tested including: 1) knowledge interventions; 2) lifestyle interventions; 3) skills training interventions; and 4) patient activation and empowerment interventions. Most of these interventions have been tested individually, but rarely have they been tested in combination, especially among African Americans who have the greatest burden of diabetes related complications. This study provides a unique opportunity to address this gap in the literature. METHODS/DESIGN: We describe an ongoing four-year randomized clinical trial, using a 2 x 2 factorial design, which will test the efficacy of separate and combined telephone-delivered, diabetes knowledge/information and motivation/behavioral skills training interventions in high risk African Americans with poorly controlled T2DM (HbA1c >or= 9%). Two-hundred thirty-two (232) male and female African-American participants, 18 years of age or older and with an HbA1c >or= 9%, will be randomized into one of four groups for 12-weeks of phone interventions: (1) an education group, (2) a motivation/skills group, (3) a combined group or (4) a usual care/general health education group. Participants will be followed for 12-months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that among African Americans with poorly controlled T2DM, patients randomized to the combined diabetes knowledge/information and motivation/behavioral skills training intervention will have significantly greater reduction in HbA1c at 12 months of follow-up compared to the usual care/general health education group. DISCUSSION: Results from this study will provide important insight into how best to deliver diabetes education and skills training in ethnic minorities and whether combined knowledge/information and motivation/behavioral skills training is superior to the usual method of delivering diabetes education for African Americans with poorly controlled T2DM. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00929838). PMID- 20350324 TI - Abdominal wall and labial edema presenting in a girl with Henoch-Schonlein purpura: a case report. AB - INTRODUCTION: Henoch-Schonlein purpura is a common immunoglobulin A-mediated vasculitic syndrome in children, characterized by purpuric rash, arthritis and abdominal pain. Renal involvement, manifested by the presence of hematuria and/or proteinuria, is also frequently seen. In most cases, patients with this disease achieve complete recovery, but some progress to renal impairment. Gastro intestinal manifestations are present in two-thirds of affected patients and range from vomiting, diarrhea, and peri-umbilical pain to serious complications such as intussusception and gastrointestinal hemorrhage. CASE PRESENTATION: We report the case of a 7-year-old Caucasian girl who presented with abdominal pain, labial swelling, and a large abdominal ecchymosis two weeks after having been diagnosed with Henoch-Schonlein purpura. A computed tomography scan revealed abdominal wall edema extending to the groin, without any intra-abdominal pathology. She was successfully treated with intravenous steroids. CONCLUSION: Circumferential anterior abdominal wall edema and labial edema have never been reported previously, to the best of our knowledge, as a complication of Henoch Schonlein purpura. These findings further contribute to the wide spectrum of manifestations of this disorder in the literature, aiding in its recognition and management. PMID- 20350325 TI - A 2cM genome-wide scan of European Holstein cattle affected by classical BSE. AB - BACKGROUND: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with variations in transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism (SNP) markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic. RESULTS: Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set of paired cases with controls. The family set comprises half-sibling progeny from six sires. The progeny from four of these sires had previously been scanned with microsatellite markers. The results obtained from the current analysis of the family set yielded both some supporting and new results compared with those obtained in the earlier study. The results revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease. These results confirm a region previously reported on chromosome 20, and identify additional regions on chromosomes 2, 14, 16, 21 and 28. This study did not identify a significant association near the PRNP in the family sample set. The only association found in the PRNP region was in the case-control sample set and this was not significant after multiple test correction. The genome scan of the case-control animals did not identify any associations that passed a stringent genome-wide significance threshold. CONCLUSIONS: Several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. Further investigation of loci on chromosomes 2, 14, 16, 20, 21 and 28 will be required to uncover any biological significance underlying these marker associations. PMID- 20350327 TI - Incidence of self-reported brain injury and the relationship with substance abuse: findings from a longitudinal community survey. AB - BACKGROUND: Traumatic or serious brain injury (BI) has persistent and well documented adverse outcomes, yet 'mild' or 'moderate' BI, which often does not result in hospital treatment, accounts for half the total days of disability attributed to BI. There are currently few data available from community samples on the incidence and correlates of these injuries. Therefore, the study aimed to assess the 1) incidence of self-reported mild (not requiring hospital admission) and moderate (admitted to hospital)) brain injury (BI), 2) causes of injury 3) physical health scores and 4) relationship between BI and problematic alcohol or marijuana use. METHODS: An Australian community sequential-cohort study (cohorts aged 20-24, 40-44 and 60-64 years at wave one) used a survey methodology to assess BI and substance use at baseline and four years later. RESULTS: Of the 7485 wave one participants, 89.7% were re-interviewed at wave two. There were 56 mild (230.8/100000 person-years) and 44 moderate BI (180.5/100000 person-years) reported between waves one and two. Males and those in the 20-24 year cohort had increased risk of BI. Sports injury was the most frequent cause of BI (40/100) with traffic accidents being a greater proportion of moderate (27%) than mild (7%) BI. Neither alcohol nor marijuana problems at wave one were predictors of BI. BI was not a predictor of developing substance use problems by wave two. CONCLUSIONS: BI were prevalent in this community sample, though the incidence declined with age. Factors associated with BI in community samples differ from those reported in clinical samples (e.g. typically traumatic brain injury with traffic accidents the predominate cause). Further, detailed evaluation of the health consequences of these injuries is warranted. PMID- 20350328 TI - A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study. AB - BACKGROUND: There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. METHODS: The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine oligoethylene glycol ligands. RESULTS: The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. CONCLUSIONS: These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art. PMID- 20350326 TI - Evidence for perinatal and child health care guidelines in crisis settings: can Cochrane help? AB - BACKGROUND: It is important that healthcare provided in crisis settings is based on the best available research evidence. We reviewed guidelines for child and perinatal health care in crisis situations to determine whether they were based on research evidence, whether Cochrane systematic reviews were available in the clinical areas addressed by these guidelines and whether summaries of these reviews were provided in Evidence Aid. METHODS: Broad internet searches were undertaken to identify relevant guidelines. Guidelines were appraised using AGREE and the clinical areas that were relevant to perinatal or child health were extracted. We searched The Cochrane Database of Systematic Reviews to identify potentially relevant reviews. For each review we determined how many trials were included, and how many were conducted in resource-limited settings. RESULTS: Six guidelines met selection criteria. None of the included guidelines were clearly based on research evidence. 198 Cochrane reviews were potentially relevant to the guidelines. These reviews predominantly addressed nutrient supplementation, breastfeeding, malaria, maternal hypertension, premature labour and prevention of HIV transmission. Most reviews included studies from developing settings. However for large portions of the guidelines, particularly health services delivery, there were no relevant reviews. Only 18 (9.1%) reviews have summaries in Evidence Aid. CONCLUSIONS: We did not identify any evidence-based guidelines for perinatal and child health care in disaster settings. We found many Cochrane reviews that could contribute to the evidence-base supporting future guidelines. However there are important issues to be addressed in terms of the relevance of the available reviews and increasing the number of reviews addressing health care delivery. PMID- 20350329 TI - Large-scale analysis of full-length cDNAs from the tomato (Solanum lycopersicum) cultivar Micro-Tom, a reference system for the Solanaceae genomics. AB - BACKGROUND: The Solanaceae family includes several economically important vegetable crops. The tomato (Solanum lycopersicum) is regarded as a model plant of the Solanaceae family. Recently, a number of tomato resources have been developed in parallel with the ongoing tomato genome sequencing project. In particular, a miniature cultivar, Micro-Tom, is regarded as a model system in tomato genomics, and a number of genomics resources in the Micro-Tom-background, such as ESTs and mutagenized lines, have been established by an international alliance. RESULTS: To accelerate the progress in tomato genomics, we developed a collection of fully-sequenced 13,227 Micro-Tom full-length cDNAs. By checking redundant sequences, coding sequences, and chimeric sequences, a set of 11,502 non-redundant full-length cDNAs (nrFLcDNAs) was generated. Analysis of untranslated regions demonstrated that tomato has longer 5'- and 3'-untranslated regions than most other plants but rice. Classification of functions of proteins predicted from the coding sequences demonstrated that nrFLcDNAs covered a broad range of functions. A comparison of nrFLcDNAs with genes of sixteen plants facilitated the identification of tomato genes that are not found in other plants, most of which did not have known protein domains. Mapping of the nrFLcDNAs onto currently available tomato genome sequences facilitated prediction of exon-intron structure. Introns of tomato genes were longer than those of Arabidopsis and rice. According to a comparison of exon sequences between the nrFLcDNAs and the tomato genome sequences, the frequency of nucleotide mismatch in exons between Micro-Tom and the genome-sequencing cultivar (Heinz 1706) was estimated to be 0.061%. CONCLUSION: The collection of Micro-Tom nrFLcDNAs generated in this study will serve as a valuable genomic tool for plant biologists to bridge the gap between basic and applied studies. The nrFLcDNA sequences will help annotation of the tomato whole-genome sequence and aid in tomato functional genomics and molecular breeding. Full-length cDNA sequences and their annotations are provided in the database KaFTom http://www.pgb.kazusa.or.jp/kaftom/ via the website of the National Bioresource Project Tomato http://tomato.nbrp.jp. PMID- 20350331 TI - A cross-sectional study on health and physical functioning in relation to coping strategies among community-dwelling, ethnically diverse older women. AB - BACKGROUND: Although empirical evidence is available on the coping-health link in older age, research on this topic is needed with non-clinical samples of ethnically diverse older women. To contribute to filling such a research gap, we tested whether these women's general health and functional limitations were associated with specific coping strategies (selected for their particular relevance to health issues) and with known health-related demographics, i.e., age, ethnicity, income, and married status. METHODS: In this cross-sectional study, respondents were recruited at community facilities including stores and senior centers. The sample consisted of 180 community-dwelling women (age 52-98) screened for dementia; 64% of them reported having an ethnic minority status. The assessment battery contained the Mini-Cog, a demographics list, the Brief COPE, and the Medical Outcome Study 36-Item Short-Form Health Survey. RESULTS: Hierarchical multiple regression analyses showed that older women who used behavioral disengagement and, to a smaller degree, self-distraction as a form of coping reported lower levels of general health. The opposite was the case for positive reframing and, to a lesser degree, substance use. Moreover, lower income was related to worse general health and (together with more advanced age) physical functioning. None of the coping strategies achieved significance in the physical functioning model. CONCLUSIONS: These cross-sectional findings need corroboration by longitudinal research prior to developing related clinical interventions. Based on the initial evidence provided herein, clinicians working with this population should consider establishing the therapeutic goal of increasing the use of positive reframing while diminishing behavioral disengagement. PMID- 20350330 TI - Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD. AB - BACKGROUND: Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD. METHODS: We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA. RESULTS: In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of gamma-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a gamma sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million. CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population. PMID- 20350332 TI - Magnetic resonance imaging with pathological correlation in a case of mantle cell lymphoma of the parotid gland: a case report. AB - INTRODUCTION: Mantle cell lymphoma is a rare non-Hodgkin's lymphoma. It is a subtype of B-cell lymphoma with frequent involvement of the bone marrow and the gastrointestinal tract. Isolated parotid gland involvement seldom occurs. Here we report an unusual case of isolated infiltration of the parotid gland by mantle cell lymphoma. The aim of our study is to correlate magnetic resonance imaging findings with the histological features of the disease. To the best of our knowledge, no similar radiological findings of mantle cell lymphoma have been published before. CASE PRESENTATION: A 72-year-old Caucasian woman presented with a painful left parotid enlargement. She was diagnosed with mantle cell lymphoma involving the left submandibular gland seven years prior to presentation. Her whole body CT scan showed the absence of pathologically enlarged lymph nodes. However, a magnetic resonance imaging showed enlargement of her left parotid gland and an abnormal parenchyma with mixed-type solid and cystic lesions. A biopsy of her left parotid gland and subsequent histological examination confirmed a mantle cell lymphoma (common variant) relapse. CONCLUSION: Although rare, the involvement of parotid gland with mantle cell lymphoma must be considered in the differential diagnosis of parotid tumors. PMID- 20350333 TI - A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy. AB - BACKGROUND: The endothelin system is implicated in the pathogenesis of melanoma. We evaluated the effects of bosentan - a dual endothelin receptor antagonist - in patients receiving first-line dacarbazine therapy for stage IV metastatic cutaneous melanoma in a phase 2, proof-of-concept study. RESULTS: Eligible patients had metastatic cutaneous melanoma naive to chemotherapy or immunotherapy, no central nervous system involvement, and serum lactate dehydrogenase <1.5 x upper limit of normal. Treatment comprised bosentan 500 mg twice daily or matching placebo, in addition to dacarbazine 1000 mg/m2 every three weeks. Eighty patients were randomized (double-blind) and 38 in each group received study treatment. Median time to tumor progression (primary endpoint) was not significantly different between the two groups (placebo, 2.8 months; bosentan, 1.6 months; bosentan/placebo hazard ratio, 1.144; 95% CI, 0.717-1.827; p = 0.5683). Incidences of most adverse events and clinically relevant increases in hepatic transaminases were similar between treatment groups although hemoglobin decrease to >8 and < or = 10 g/dL and < or = 8 g/dL was more common in the bosentan group. CONCLUSIONS: In patients receiving dacarbazine as first-line chemotherapy for metastatic melanoma, the addition of high-dose bosentan had no effect on time to tumor progression or other efficacy parameters. There were no unexpected safety findings. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov under the unique identifier NCT01009177. PMID- 20350335 TI - Transcatheter closure of the arterial duct without arterial access. AB - OBJECTIVE: To evaluate the safety and efficacy of transcatheter occlusion of the arterial duct without femoral arterial catheterization. BACKGROUND: Patent arterial ducts have been closed percutaneously since the 1960s. It remains standard practice to use arterial access for aortography before, during, and after implantation of the device. Femoral arterial catheterisation has well recognised complications, and should be avoided unless absolutely necessary. METHODS: We reviewed prospectively collected data relating to 389 occlusions of the arterial duct performed consecutively between 1994 and 2004. We inserted Cook detachable coils in 288 instances using the Amplatzer duct occluder in the remaining 101. Information was obtained regarding procedural success, displacement of the device, and re-intervention. We have followed out patients for a median of 1.15 years in those closed with the Amplatzer device, and 1.09 years in those closed with a coil. RESULTS: In the patients in whom we used coils, occlusion was possible in 75% using venous access alone. We reintervened in 25 patients, because of embolisation of the device in 6, haemolysis in 5, and residual shunting in 14. On follow-up, complete occlusion had been achieved in 98%. We found trivial stenosis of the left pulmonary artery in 3 patients. When using the Amplatzer device, closure using venous access alone was achieved in 82%, and 2 patients required reintervention because of embolisation of the device. Complete occlusion had been achieved in all patients as judged by follow up at 1 year, and 2 patients had trivial stenosis of the left pulmonary artery. CONCLUSION: Arterial catheterisation is unnecessary in the great majority of patients undergoing occlusion of the arterial duct. Use of venous catheterisation alone is safe, and does not appear to increase the risk of device-related complications. PMID- 20350334 TI - Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar). AB - BACKGROUND: The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult) and in the parr-smolt transformation. RESULTS: Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1), which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta globin and guanine nucleotide binding protein (G protein) beta polypeptide 2-like 1 (GNB2L1) were also examined in adult maturing testes. Down-regulation of anti Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For anti-Mullerian hormone and guanine nucleotide binding protein beta polypeptide 2-like 1 expression changes in precocious males mirrored mature adults (November) but for collagen 1A and beta-globin the pattern was more complex. CONCLUSIONS: Expression changes in the fish brain during the process of precocious sexual maturation were small compared to those in the testes. Microarray analysis suggested down-regulation of housekeeping functions and up regulation of a small number of specific processes. Transcriptional changes in the testes were much more pronounced with anti-Mullerian hormone playing a major role. Expression profiles for mature parr and maturing adult testes indicate subtle differences in gene expression between these two related groups. PMID- 20350336 TI - Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. AB - Inflammatory/immunological process and glial contribution are suggested in the pathophysiology of schizophrenia. We investigated peripheral benzodiazepine receptors in brains of patients with chronic schizophrenia, which were reported to be located on mitochondria of glial cells, using [11C]DAA1106 with positron emission tomography. Fourteen patients and 14 age- and sex-matched normal controls participated in this study. PET data were analysed by two-tissue compartment model with metabolite-corrected plasma input. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale. There was no significant difference between [11C]DAA1106 binding of the cortical regions of normal controls and patients with schizophrenia, whereas the patients showed a positive correlation between cortical [11C]DAA1106 binding and positive symptom scores. There was also a positive correlation between [11C]DAA1106 binding and duration of illness. Although the correlations need to be interpreted very cautiously, involvement of glial reaction process in the pathophysiology of positive symptoms or progressive change of schizophrenia might be suggested. PMID- 20350337 TI - Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution. PMID- 20350338 TI - Confidence bounds for the estimation of the volume phase fraction from a single image in a nickel base superalloy. AB - We propose an image-based framework to evaluate the uncertainty in the estimation of the volume fraction of specific microstructures based on the observation of a single section. These microstructures consist of cubes organized on a cubic mesh, such as monocrystalline nickel base superalloys. The framework is twofold: a model-based stereological analysis allows relating two-dimensional image observations to three-dimensional microstructure features, and a spatial statistical analysis allows computing approximate confidence bounds while assessing the representativeness of the image. The reliability of the method is assessed on synthetic models. Volume fraction estimation variances and approximate confidence intervals are computed on real superalloy images in the context of material characterization. PMID- 20350339 TI - Three-dimensional optical sectioning by scanning confocal electron microscopy with a stage-scanning system. AB - We evaluated the depth resolution of annular dark-field (ADF) scanning confocal electron microscopy (SCEM) with a stage-scanning system by observation of nanoparticles. ADF-SCEM is a three-dimensional (3D) imaging technique that we recently proposed. An ADF-SCEM instrument involves a pinhole aperture before a detector for rejecting electrons from the out-of-focal plane in a specimen and an annular aperture under the specimen for collecting only scattered electrons. The stage-scanning system enables us to directly obtain optical slice images perpendicular and parallel to an optical axis at a desired position. In particular, the parallel slices visualize the elongation of nanoparticles along the optical axis, which depends on the depth resolution. ADF-SCEM effectively reduced the elongation length of the nanoparticles sufficiently to demonstrate depth sectioning, in comparison with scanning transmission electron microscopy and bright-field SCEM. The experimentally obtained length was nearly equal to the theoretically estimated one from the probe size considering the experimental conditions. Furthermore, we applied this ADF-SCEM technique to analysis of the 3D position of catalytic nanoparticles on carbon nanostructures. PMID- 20350340 TI - Polarized-light interferometry of calcium carbonate deposition in moss from a waterfall on the niagara escarpment. AB - Deposition of calcium carbonate from groundwater was examined on a moss, Didymodon tophaceus, from a Niagara Escarpment waterfall. A spectrophotometer on a polarizing microscope was used for interferometry. A second-order blue interference with an interference minimum around 620 nm was found when moss cell spaces were fully calcified. Filled cell spaces were often surrounded by empty cell spaces. Complete calcification of whole leaflets resulted in progressively higher orders of interference colors and a positive shift in interference minima. Calcified leaflets finally became cemented together, but each retained a weak extinction when rotated. Small calcareous spherulites (mean diameter 15.7 +/- 2.1 microm) were found between leaflets. Spherulites exhibited first-order white interference with a Maltese cross that rotated when the polarizer and analyzer were rotated in tandem. A Nikitin-Berek compensator was tilted at 5.5 degrees to give an interference minimum at 600 nm in the optical axis. Quadrants of spherulites with radii more or less in line with the tilting axis of the compensator had lower (P < 0.001) interference minima (535 +/- 27 nm) than quadrants with radii more or less perpendicular to the compensator (659 +/- 15 nm), thus indicating a radial internal structure. Spherulites were tentatively identified as vaterite. PMID- 20350341 TI - Study of molecular targets influencing homocysteine and cholesterol metabolism in growing rats by manipulation of dietary selenium and methionine concentrations. AB - Inconsistent results exist from human and animal studies for Se and methionine (Met) regarding their influence on homocysteine (HCys) and cholesterol (Chol) metabolism. To elucidate these contradictions, sixty-four weanling albino rats were divided into eight groups of 8, and were fed diets containing four different Se levels (15, 50, 150 and 450 microg/kg) either in combination with the recommended Met level of 3 g/kg (C15, C50, C150 and C450) or with an increased Met concentration of 15 g/kg (M15, M50, M150 and M450) for 8 weeks. Plasma HCys was twofold higher in the Se-supplemented C groups than in group C15. Met addition also doubled plasma HCys compared with the respective C groups. In contrast, the expression of the key enzymes of glutathione biosynthesis in the liver was significantly lowered by Se and in particular by Met. Liver Chol concentration was significantly higher in all the Se-supplemented C and M groups than in groups C15 and M15. Plasma Chol was, however, lowered. The uninfluenced expression of sterol-regulatory element-binding protein 2 and of hydroxymethyl glutaryl-CoA reductase, the increased LDL receptor expression and the reduced expression of the hepatobiliary Chol exporter ATP-binding-cassette-transporter 8 (ABCG8) by Se and/or Met explain these findings. We conclude that the elevation of plasma HCys in rats by Se and Met results from a higher export into plasma. The fact that Se in particular combined with Met increases liver Chol but reduces plasma Chol should be addressed in future investigations focussing on the regulation of ABCG8, which is also selectively involved in the reverse transport of phytosterols in the small intestine. PMID- 20350342 TI - Role of induced abortion in attaining reproductive goals in Kyrgyzstan: a study based on KRDHS-1997. AB - Estimates indicate that about 42 million pregnancies are voluntarily terminated every year at the global level, of which more than 80% occur in developing countries. Abortion has been one of the major reproductive health concerns in post-Soviet nations, especially when it is commonly used as a means of fertility regulation. On average, every woman has had around 1.6 abortions in Kyrgyzstan. This paper attempts to measure the role of abortion in fertility regulation using data from the Kyrgyz Republic Demographic and Health Survey (KRDHS), 1997. The analysis reveals that Kyrgyzstan can attain replacement level fertility in the absence of induced abortion by raising the contraceptive prevalence to 70% at the current level of effectiveness. The study also shows that women's attitude towards becoming pregnant and their partner's perception about abortion are significantly associated with the propensity to opt for an induced abortion. Reproductive health programmes need to address these issues, including the enhancement of male involvement in family planning. PMID- 20350343 TI - Virgin olive oil administration improves the effect of aspirin on retinal vascular pattern in experimental diabetes mellitus. AB - The aim of the present study is to evaluate the possible influence of virgin olive oil (VOO) on the effect of acetylsalicylic acid (ASA) in platelet aggregation, prostanoid and NO production and retinal vascular pattern in rats with experimental type 1-like diabetes. We used 100 male Wistar rats that were distributed into five groups: (1) non-diabetic rats (NDR); (2) untreated diabetic rats (DR); (3) DR treated with ASA (2 mg/kg per d per os (p.o.)); (4) DR treated with VOO (0.5 ml/kg per d p.o.); (5) DR treated with ASA plus VOO. The duration of diabetes was 3 months, and each treatment was administered from the first day of diabetes. Variables that were quantified were platelet aggregation (I(max)), thromboxane B(2) (TxB(2)), aortic prostacyclin (6-keto-PGF(1alpha)) and NO, and the percentage of retina with horseradish peroxidase-permeable vessels (HRP-PV). Diabetic rats showed a higher I(max) (35 %) and TxB(2) (63 %) than NDR, and a lower 6-keto-PGF(1alpha), NO and HRP-PV than NDR ( - 74.6 %). ASA and VOO administration reduced these differences and prevented the percentage of HRP-PV ( - 59.7 % with ASA and - 46.7 % with VOO). The administration of ASA plus VOO showed a strong platelet inhibition (80.2 v. 23.4 % for VOO and 50.6 % for ASA+VOO, P < 0.0001), and reduced HRP-PV differences to - 31.6 % (P < 0.001 with respect to DR and P < 0.0001 with respect to DR treated with ASA). In conclusion, the administration of VOO to rats with type 1-like diabetes mellitus improves the pharmacodynamic profile of ASA, and increases its retinal anti-ischaemic effect. PMID- 20350345 TI - Effect of the nationwide free school fruit scheme in Norway. AB - In Norway, children and adolescents consume only about half of the national five a-day recommendation. There are also rather large social inequalities in health, and in eating behaviours. In order to increase fruit and vegetable (FV) intake, a subscription programme was initiated in 1996 and made nationwide in 2003, and a free programme (without parental payment) has been implemented nationwide from 2007. The objective of the present study is to evaluate the effect of these efforts. Pupils in the sixth and seventh grades (age 10-12 years) at twenty-seven schools responded to a questionnaire in 2001 (n 1488, 85 %) and in 2008 (n 1339, 78 %). FV intake was measured by a 24-h recall. In 2001, none of the schools had any organised school fruit programme. In 2008, five schools participated in the free school fruit programme, ten schools participated in the subscription programme and twelve schools did not participate in any official programme. The increases in fruit intake at school were 0.49, 0.29 and 0.18 portions/school day, respectively, for the Free Fruit 08, Subscription 08 and No Programme 08 schools (time x group P < 0.001), and 0.74, 0.39 and 0.16 portions/d for fruit intake all day (time x group P = 0.04). No group effect was observed for vegetable intake. There has been an increase in pupils' fruit intake from 2001 to 2008 in Norway, and the school fruit programmes seem to have been effective. A great challenge remains in increasing vegetable intake. PMID- 20350344 TI - A randomised study on the clinical progress of high-risk elective major gastrointestinal surgery patients treated with olive oil-based parenteral nutrition with or without a fish oil supplement. AB - n-3 Fatty acids have clinical benefits. The primary aim of the present study was the assessment of infection in patients who underwent major high-risk elective gastrointestinal surgery receiving postoperatively fish oil (FO)-supplemented parenteral nutrition (PN), compared with those receiving a standard olive oil (OO) emulsion. The secondary aims were the assessment of anti-inflammatory response and evaluation of tolerance and safety of these emulsions. A prospective, randomised, double-blind study was performed in patients requiring at least 5 d of PN. An isoenergetic and isoproteic formula was administered: group A received OO alone, while group B received OO that was partially replaced with FO (16.6 %, w/w). End points were outcome measures (mortality, sepsis, infection, hospitalisation days and PN duration), inflammatory response (C reactive protein (CRP), prealbumin and leucocytes) and safety (TAG and glucose metabolism, and liver and kidney function). Statistical analysis was done using Student's t test and Fisher's exact test (P < 0.05). Twenty-seven patients were evaluated, with thirteen patients receiving FO. In this group, a significantly lower incidence of infections was found (23.1 v. 78.6 %, P = 0.007). CRP, prealbumin and leucocytes were not significantly different between the groups. There were no differences in safety parameters. We conclude that high-risk surgical patients receiving FO-supplemented PN for 5 d present a lower incidence of infection. Emulsions were safe and well tolerated. PMID- 20350346 TI - Comparison of transplant efficiency between spontaneously derived and noggin primed human embryonic stem cell neural precursors in the quinolinic acid rat model of Huntington's disease. AB - Human neural precursors (hNP) derived from embryonic stem cells (hESC) may provide a viable cellular source for transplantation therapy for Huntington's disease (HD). However, developing effective transplantation therapy for the central nervous system (CNS) using hESC relies on optimizing the in vitro production of hNP to control appropriate in vivo posttransplantation neuronal differentiation. The current study provides the first direct in vivo comparison of the transplant efficiency and posttransplantation characteristics of spontaneously derived and noggin-primed hNP following transplantation into the quinolinic acid (QA) rat model of HD. We show that spontaneously derived and noggin-primed hNP both survived robustly up to 8 weeks after transplantation into the QA-lesioned striatum of the adult rat. Transplanted hNP underwent extensive migration and large-scale differentiation towards a predominantly neuronal fate by 8 weeks posttransplantation. Furthermore, in vitro noggin priming of hNP specifically increased the extent of neuronal differentiation at both 4 and 8 weeks posttransplantation when compared to spontaneously derived hNP grafts. The results of this study suggest that in vitro noggin priming provides an effective mechanism by which to enhance hNP transplant efficiency for the treatment of HD. PMID- 20350347 TI - Adenosine A(2A) agonist administration improves islet transplant outcome: Evidence for the role of innate immunity in islet graft rejection. AB - Activation of adenosine A(2A) receptors inhibits inflammation in ischemia/reperfusion injury, and protects against cell damage at the injury site. Following transplantation 50% of islets die due to inflammation and apoptosis. This study investigated the effects of adenosine A(2A) receptor agonists (ATL146e and ATL313) on glucose-stimulated insulin secretion (GSIS) in vitro and transplanted murine syngeneic islet function in vivo. Compared to vehicle controls, ATL146e (100 nM) decreased insulin stimulation index [SI, (insulin)(high glucose)/(insulin)(low glucose)] (2.36 +/- 0.22 vs. 3.75 +/- 0.45; n = 9; p < 0.05). Coculture of islets with syngeneic leukocytes reduced SI (1.41 +/- 0.17; p < 0.05), and this was restored by ATL treatment (2.57 +/- 0.18; NS). Addition of a selective A(2A)AR antagonist abrogated ATL's protective effect, reducing SI (1.11 +/- 0.42). ATL treatment of A(2A)AR(+/+) islet/A(2A)AR(-/-) leukocyte cocultures failed to protect islet function (SI), implicating leukocytes as likely targets of A(2A)AR agonists. Diabetic recipient C57BL/6 mice (streptozotocin; 250 mg/kg, IP) received islet transplants to either the renal subcapsular or hepatic-intraportal site. Recipient mice receiving ATL therapy (ATL 146e or ATL313, 60 ng/kg/min, IP) achieved normoglycemia more rapidly than untreated recipients. Histological examination of grafts suggested reduced cellular necrosis, fibrosis, and lymphocyte infiltration in agonist-treated animals. Administration of adenosine A(2A) receptor agonists (ATL146e or ATL313) improves in vitro GSIS by an effect on leukocytes, and improves survival and functional engraftment of transplanted islets by inhibiting inflammatory islet damage in the peritransplant period, suggesting a potentially significant new strategy for reducing inflammatory islet loss in clinical transplantation. PMID- 20350348 TI - Limited penetration of perfluorocarbon in porcine pancreas preserved by two-layer method with (19)fluorine magnetic resonance spectroscopy and headspace gas chromatography. AB - The mechanism of the two-layer method (TLM) of pancreas preservation is unclear. Facilitating oxygen diffusion into preserved pancreas has been suggested, but direct measurements of tissue pO(2) have yielded conflicting results. The degree of penetration of perfluorocarbon (PFC) into the pancreas during TLM storage is unknown. Segments of porcine pancreas (7.5 cm in length) were preserved either in University of Wisconsin solution (UW) alone (n = 6) or in TLM for 24 h (n = 6). Pancreatic samples were analyzed using Varian INOVA 9.4 T MR scanner. External PFC standard was introduced for quantification. Four consecutive transverse images of 4 mm thickness were obtained using a spin-echo sequence. (19)Fluorine magnetic resonance spectroscopy ((19)F MRS) was performed with the same parameters except with more averages. MR data were confirmed by headspace chromatography. PFC standard was readily detected in (19)F MR images. There was no signal from pancreas in (19)F MR images following either UW or TLM storage. (19)F MR spectra typical of PFC were not obtained from either UW- or TLM preserved pancreas with nonlocalized (19)F MRS. Mean concentration of PFC in TLM pancreas measured by head space chromatography was 0.011 nl/g (SD +/- 0.006), not significantly different from background concentration (0.012 nl/g, SD +/- 0.006) in UW pancreas (p = 0.42). There was no evidence of penetration of PFC into pancreas tissues investigated either by MR or chromatography in organs preserved at hypothermia by TLM, and mechanisms of TLM remain speculative. PMID- 20350349 TI - Human mesenchymal stromal cells and their derivative, SB623 cells, rescue neural cells via trophic support following in vitro ischemia. AB - Cell transplantation is a promising treatment strategy for many neurological disorders, including stroke, which can target multiple therapeutic mechanisms in a sustained fashion. We investigated the ability of human mesenchymal stromal cells (MSCs) and MSC-derived SB623 cells to rescue neural cells via trophic support following an in vitro stroke model. Following oxygen glucose deprivation, cortical neurons or hippocampal slices were cocultured with either MSCs or SB623 cells separated by a semiporous membrane (prohibits cell-cell contact) or with MSC- or SB623 cell-conditioned medium. MSCs, SB623 cells, MSC-conditioned media, and SB623 cell-conditioned media all significantly reduced neural cell damage/death compared to untreated conditions, and the rescue effect of the conditioned media was dose dependent. We identified 11 neurotrophic factors secreted by MSCs and/or SB623 cells. This study emphasizes the importance of trophic support provided by marrow-derived cells, which likely contributes to the efficacy of cell therapy for brain injury. PMID- 20350350 TI - Embryonic stem cell-derived glial precursors as a vehicle for sulfamidase production in the MPS-IIIA mouse brain. AB - Pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, have generated much excitement about their prospects for use in cell transplantation therapies. This is largely attributable to their virtually unlimited growth potential, their ability to be precisely genetically altered in culture, and their utility for forming differentiated cell populations with potential clinical applications. Lysosomal storage diseases such as Sanfilippo syndrome (MPS-IIIA) represent ideal candidate diseases for the evaluation of cell therapies in the central nervous system (CNS). These diseases exhibit widespread pathology yet result from a single gene deficiency, in the case of Sanfilippo syndrome the lysosomal enzyme sulfamidase. The aim of this study was to investigate mouse embryonic stem (ES) cell-derived glial precursor cells as a vehicle for sulfamidase delivery in the MPS-IIIA mouse brain. In this study we have created a mouse ES cell line genetically modified to stably express and secrete high levels of human sulfamidase and a protocol for the in vitro derivation of large numbers glial precursors from ES cells. Differentiation of sulfamidase-expressing ES cells resulted in cell populations with sustained secretion of high levels of sulfamidase, comprised primarily of glial precursor cells with minor contaminants of other neural cell phenotypes but not residual pluripotent cells. CNS implantation studies demonstrated that ES cell-derived glial precursor cells formed using this differentiation method were able to engraft and survive for at least 12 weeks following implantation. The percentage of engraftment was quantified in different regions of the brain in 2-, 4-, and 8 week-old normal and MPS-IIIA mice. No teratomas were observed in any of the cell transplanted animals. The results of this study support the further investigation of sulfamidase-expressing glial precursor cells as a vehicle for delivery of deficient enzyme into the CNS of MPS-IIIA mice. PMID- 20350351 TI - Effects of MRI contrast agents on the stem cell phenotype. AB - The ultimate therapy for ischemic stroke is restoration of blood supply in the ischemic region and regeneration of lost neural cells. This might be achieved by transplanting cells that differentiate into vascular or neuronal cell types, or secrete trophic factors that enhance self-renewal, recruitment, long-term survival, and functional integration of endogenous stem/progenitor cells. Experimental stroke models have been developed to determine potential beneficial effect of stem/progenitor cell-based therapies. To follow the fate of grafted cells in vivo, a number of noninvasive imaging approaches have been developed. Magnetic resonance imaging (MRI) is a high-resolution, clinically relevant method allowing in vivo monitoring of cells labeled with contrast agents. In this study, labeling efficiency of three different stem cell populations [mouse embryonic stem cells (mESC), rat multipotent adult progenitor cells (rMAPC), and mouse mesenchymal stem cells (mMSC)] with three different (ultra)small superparamagnetic iron oxide [(U)SPIO] particles (Resovist, Endorem, Sinerem) was compared. Labeling efficiency with Resovist and Endorem differed significantly between the different stem cells. Labeling with (U)SPIOs in the range that allows detection of cells by in vivo MRI did not affect differentiation of stem cells when labeled with concentrations of particles needed for MRI-based visualization. Finally, we demonstrated that labeled rMAPC could be detected in vivo and that labeling did not interfere with their migration. We conclude that successful use of (U)SPIOs for MRI-based visualization will require assessment of the optimal (U)SPIO for each individual (stem) cell population to ensure the most sensitive detection without associated toxicity. PMID- 20350353 TI - Transplantation of cultured autologous melanocytes: hope or danger? AB - Cultured human melanocytes are increasingly being used in the treatment of vitiligo. The growth media contain various types of mitogenic factors, both recombinant human (e.g., rhbFGF and rhSCF) and synthetic (e.g., TPA). High concentrations of mitogenic factors accelerate the cell cycle, and consequently may increase the risk of carcinogenesis of transplanted cells. Mutations of genes of the RAS/RAF/MEK/ERK signaling pathway are very often found in the early stages of the development of melanoma. TPA is considered to be an oncogenic factor, but so far there is no evidence to show that it is responsible for damage to the genetic material of cultured melanocytes. The aim of our study was to assess the risk of the development of mutations in selected genes of the RAS/RAF/MEK/ERK signaling pathway during the culturing of melanocytes in various growth media. Based on the results obtained, it can be concluded that TPA and high concentrations of other growth factors intensify the proliferation of melanocytes, without the risk of damage to the HRAS (exon 1 and 2), KRAS (exon 1 and 2), NRAS (exon 1 and 2), and BRAF (exon 11 and 15) genes. In order to assess the total safety of the transplantation of cultured melanocytes, it is necessary to carry out further studies on other signaling pathways as well as carry out biological tests on an animal model. PMID- 20350352 TI - Distribution, differentiation, and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis. AB - The transplantation of neural stem cells (NSCs) is a challenging therapeutic strategy for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). To provide insight into the potential of the intravenous delivery of NSCs, we evaluated the delivery of NSCs marked with green fluorescent protein to the central nervous system (CNS) via intravenous tail vein injections in an ALS model. The injected cell fates were followed 1, 3, and 7 days after transplantation. The highest efficiency of cell delivery to the CNS was found in symptomatic ALS (up to 13%), moderate in presymptomatic ALS (up to 6%), and the lowest in wild-type animals (up to 0.3%). NSCs injected into ALS animals preferentially colonized the motor cortex, hippocampus, and spinal cord, and their differentiation was characterized by a decrease of nestin expression and the appearance of MAP2-, GFAP-, O4-, and CD68-positive cells. Tumor necrosis factor (TNF) administration increased the CNS delivery of transplanted cells in wild-type and presymptomatic, but not ALS symptomatic animals. Moreover, a TNF related increase in NSC differentiation and survival was detected. Apoptosis was detected as the main cause of the loss of transplanted cells and it was influenced by TNF. Although 3 days after TNF treatment cell death was accelerated, TNF slowed down apoptosis after 7 days. This study provides elementary facts about the process occurring after NSCs leave the blood stream and enter the nervous tissue affected by inflammation/degeneration, which should help facilitate the planning of future bench-to-bedside translational projects. PMID- 20350354 TI - Prevascular structures promote vascularization in engineered human adipose tissue constructs upon implantation. AB - Vascularization is still one of the most important limitations for the survival of engineered tissues after implantation. In this study, we aim to improve the in vivo vascularization of engineered adipose tissue by preforming vascular structures within in vitro-engineered adipose tissue constructs that can integrate with the host vascular system upon implantation. Different cell culture media were tested and different amounts of human adipose tissue-derived mesenchymal stromal cells (ASC) and human umbilical vein endothelial cells (HUVEC) were combined in spheroid cocultures to obtain optimal conditions for the generation of prevascularized adipose tissue constructs. Immunohistochemistry revealed that prevascular structures were formed in the constructs only when 20% ASC and 80% HUVEC were combined and cultured in a 1:1 mixture of endothelial cell medium and adipogenic medium. Moreover, the ASC in these constructs accumulated lipid and expressed the adipocyte-specific gene fatty acid binding protein-4. Implantation of prevascularized ASC/HUVEC constructs in nude mice resulted in a significantly higher amount of vessels (37 +/- 17 vessels/mm(2)) within the constructs compared to non-prevascularized constructs composed only of ASC (3 +/- 4 vessels/mm(2)). Moreover, a subset of the preformed human vascular structures (3.6 +/- 4.2 structures/mm(2)) anastomosed with the mouse vasculature as indicated by the presence of intravascular red blood cells. Our results indicate that preformed vascular structures within in vitro-engineered adipose tissue constructs can integrate with the host vascular system and improve the vascularization upon implantation. PMID- 20350355 TI - Factors affecting residence time of mesenchymal stromal cells (MSC) injected into the myocardium. AB - The therapeutic mechanism of mesenchymal stromal/stem cells (MSC) for the treatment of acute myocardial infarction is not well understood. Our goal was to get insights into this mechanism by analyzing the survival kinetics of allogeneic and syngeneic cell transplants under different tissue conditions. Two MSC cell banks, stably and equally expressing the luciferase reporter construct, were developed for these studies and injected directly to the myocardium of Lewis rat recipients under syngeneic or allogeneic transplantation conditions. Cell survival was monitored by real-time fashion for up to 2 weeks, using optical imaging device (IVIS, Xenogen Corp.). We found that both syngeneic and allogeneic grafts reduced significantly in size during the first week of transplantation, either in the normal or in the late infarcted heart (5 days after MI) and allotransplants became always smaller than syngeneic grafts during this period. Low dose of cyclosporine A treatment had a benefit on both allo- and syngeneic graft sizes, suggesting that multiple mechanisms play a role in early graft reduction. The MSC characteristic factors IL-6, IL-8, MCP-1, and VEGF were well above the control level in the heart tissue at 4 days after cell injection, suggesting that the peak therapeutic effect of MSC can be expected during the first week of the administration. Although allogeneic cells induced immunoglobulin production, their biological effects (cell survival, factor productions) are very similar to the syngeneic transplants and therefore they could deliver the same therapeutic effect as the syngeneic cells. Finally, freshly infarcted tissue (30 min) supported better the survival of MSC than late postischemic tissue (5 days) but only "off the shelf" allogeneic cell transplants fits with this treatment strategy. PMID- 20350357 TI - Olfactory ensheathing glia transplantation combined with LASERPONCTURE in human spinal cord injury: Results measured by electromyography monitoring. AB - Preliminary results were measured by electromyography monitoring (electromyoscan) on three subjects suffering from spinal cord injury and who underwent a double therapy. The aim of this study was to evaluate regained voluntary activity below the injury in subjects who received a double therapy: 1) an olfactory ensheathing glia (OEG) transplantation using procedures developed by Dr. Hongyun Huang at the Xishan Hospital and Rehabilitation Centre, Beijing, China, and 2) LASERPONCTURE developed by Albert Bohbot, Laboratoire de Recherches sur le LASERPONCTURE, La Chapelle Montlinard, France. Materials uses were the LASERPONCTURE device developed by Albert Bohbot; the PROCOMP5 equipment with softwares BIOGRAPH INFINITI 5 and REHAB SUITE; the sensors MYOSCAN-PRO EMG (SA9401M-50) to record muscle activity, and FLEX/PRO-SA9309M to record skin conductance were fixed on the skin. An infrared laser, whose frequencies and power settings cannot be disclosed due to its proprietary nature, was applied after an OEG injection performed according to Dr. Hongyun Huang's procedures. Three cases, two males and one female, were selected for this study. Presentation and comments of the graphs recordings of voluntary muscle activity below the injury are provided. This preliminary study suggests that the double therapy restores some voluntary muscle activity as measured by electromyography monitoring. PMID- 20350359 TI - Purification of mouse bone marrow-derived stem cells promotes ex vivo neuronal differentiation. AB - The main objective of this study is to test the potential of specific populations of mouse bone marrow-derived stem cells (BMSCs) to differentiate into the neuronal cell lineage. Bone marrow of 33 mice was aspirated under general anesthesia. The collected marrows were analyzed for cell counts, compositions, and percentages of different stem cell types. We used the Midi MACS magnetic separator to purify specific populations of stem cells from the aspirated bone marrow. Cells were analyzed using flow cytometry. We assessed the presence of stem cell antigen-1 (Sca-1(+)) and prominin-1(+) cells in the cellular fraction that was depleted of lineage-committed cells (lineage(-)). Both purified and nonpurified cells were cultured ex vivo using specific growth media with factors that drive the cells to differentiate into the neuroglial cell types. Cells were then analyzed by flow cytometry for expression of specific neuronal markers. Our results showed that there was an increase of Sca-1(+) and prominin-1(+) cells in the lineage(-) fraction over the unpurified BM. After lineage depletion, the percentages of Sca-1(+) and prominin-1(+) cells increased from 4.9% and 2.6%, up to 76.1% and 59%, respectively. Unpurified mouse BM differentiated into fibroblasts, whereas Sca-1(+) cells were able to generate astrocytes. Interestingly, purified prominin-1(+) cells were able to generate neuronal cells. Purification of adult bone marrow-derived stem cells enhances their potentiality for differentiating into specific neuronal cell lineages. PMID- 20350358 TI - Death of axotomized retinal ganglion cells delayed after intraoptic nerve transplantation of olfactory ensheathing cells in adult rats. AB - Intraorbital transection of the optic nerve (ON) always induces ultimate apoptosis of retinal ganglion cells (RGCs) and consequently irreversible defects of vision function. It was demonstrated that transplanted olfactory ensheathing cells (OECs) in partially injured spinal cord have a distant in vivo neuroprotective effect on descending cortical and brain stem neurons. However, this study gave no answers to the question whether OECs can protect the central sensitive neurons with a closer axonal injury because different neurons respond variously to similar axonal injury and the distance between the neuronal soma and axonal injury site has a definite effect on the severity of neuronal response and apoptosis. In the present study, we investigated the effect of transplanted OECs on RGCs after intraorbital ON transection in adult rats. Green fluorescent protein (GFP)-OECs were injected into the ocular stumps of transected ON and a significantly higher number of surviving RGCs was found together with a consistent marked increase in the mRNA and protein levels of BDNF in the ON stump and retina in the OEC-treated group at 7 days, but not 2 and 14 days, time point when compared to the control group. Our findings suggest that OEC transplantation induces the expression of BDNF in the ocular ON stump and retina and delays the death of axotomized RGCs at a certain survival period. PMID- 20350360 TI - Intracranial transplant of olfactory ensheathing cells in children and adolescents with cerebral palsy: a randomized controlled clinical trial. AB - Successful repair of damage in cerebral palsy (CP) needs effective clinical interventions other than simply symptomatic treatments. To elucidate the feasibility of using olfactory ensheathing cells (OECs) to treat CP in children and adolescents, we conducted a randomized controlled clinical trial (RCT) on 33 patients. The patients were randomly assigned into two groups (treatment group, n = 18; control group, n = 15), and OECs derived from aborted fetal tissue were injected into the bilateral corona radiata in the frontal lobes (a key point for neural network restoration, KPNNR). The Gross Motor Function Measure (GMFM-66) and the Caregiver Questionnaire Scale were used to evaluate the patients' neurological function and overall health status. Among the 14 patients who completed the 6-month study, six received the cell transplantation and the other eight served as controls. In OEC treatment group, GMFM-66 scores were 26.67 +/- 25.33 compared with 19.00 +/- 20.00 for the control group. Concurrently, the Caregiver Questionnaire Scale score decreased to 77.83 +/- 15.99 in the treatment group in comparison to 138.66 +/- 64.06 of the control group. This trial, albeit small in sample size, indicates OEC KPNNR transplantation is effective for functional improvement in children and adolescents with CP, yet without obvious side effects. This small-scale study suggests that the procedure may be a plausible alternative method to treat this not yet curable disorder, and we urge further evaluation with a large-scale RCT. PMID- 20350361 TI - Effect of neurotrophin-3 genetically modified olfactory ensheathing cells transplantation on spinal cord injury. AB - Transplantation of olfactory ensheathing cells (OECs) has emerged as a very promising therapy for spinal cord injury (SCI). Also, local delivery of NT-3 can counteract pathological events and induce a regenerative response after SCI. Supplement of exogenetic NT-3 might be a new approach to SCI repair. In this study, we examined the therapeutic effect of rat NT-3 gene-modified OECs transplantation on SCI. Rat NT-3 gene was transfected into OECs using a retroviral system. The engineered NT-3-OECs were tested for their ability to express and secrete biologically active NT-3 in vitro. Then NT-3-OECs were implanted into contused T9 spinal cord of the adult rats. Their ability of survival and NT-3 production was examined. The effect of axon regeneration was evaluated at the morphological level and promotion of locomotor functional recovery were assessed. The result showed that genetically modified OECs were capable of surviving and producing NT-3 in vivo to significantly improve the recovery after SCI. PMID- 20350362 TI - Guidance of olfactory ensheathing cell growth and migration on electrospun silk fibroin scaffolds. AB - Transplantation of olfactory ensheathing cells (OECs) is a potential treatment for spinal cord injury (SCI). However, this process lacks extracellular matrix guiding cell growth, tissue morphogenesis, and remodeling. In order to solve this problem, we fabricated silk fibroin scaffolds (SFS) with different fiber diameters by electrospinning. The behaviors of OECs on 300 and 1800 nm SFS were studied by analyzing cell morphological feature, distribution, and proliferation. The results showed the 300 nm SFS with good potential to guide OECs growth. Subsequently, the properties of 300 nm SFS were further investigated along with PLL. With 300 nm SFS, the preservation of cell phenotype was confirmed by the presence of cell-specific markers, including nerve growth factor receptor p75 and glial fibrillary acidic protein. And the migration behaviors of OECs were also observed by Leica AF6000. In addition, migration tracks, turning behavior, migration distances, migration speeds, and forward migration indices were calculated. Furthermore, the expression of neurotrophic factors was assayed at transcription and protein levels using RT-PCR and ELISA. All these results indicated the diameter of the fiber played an important role in guiding cell adhesion, growth, and migration in vitro and the 300 nm SFS could be suitable to construct tissue-engineered scaffolds for SCI repair. PMID- 20350363 TI - Shotgun proteomics and network analysis between plasma membrane and extracellular matrix proteins from rat olfactory ensheathing cells. AB - Olfactory ensheathing cells (OECs) are a special type of glial cells that have characteristics of both astrocytes and Schwann cells. Evidence suggests that the regenerative capacity of OECs is induced by soluble, secreted factors that influence their microenvironment. These factors may regulate OECs self-renewal and/or induce their capacity to augment spinal cord regeneration. Profiling of plasma membrane and extracellular matrix through a high-throughput expression proteomics approach was undertaken to identify plasma membrane and extracellular matrix proteins of OECs under serum-free conditions. 1D-shotgun proteomics followed with gene ontology (GO) analysis was used to screen proteins from primary culture rat OECs. Four hundred and seventy nonredundant plasma membrane proteins and 168 extracellular matrix proteins were identified, the majority of which were never before reported to be produced by OECs. Furthermore, plasma membrane and extracellular proteins were classified based on their protein protein interaction predicted by STRING quantitatively integrates interaction data. The proteomic profiling of the OECs plasma membrane proteins and their connection with the secretome in serum-free culture conditions provides new insights into the nature of their in vivo microenvironmental niche. Proteomic analysis for the discovery of clinical biomarkers of OECs mechanism warrants further study. PMID- 20350364 TI - Neurorestoratology, a distinct discipline and a new era: A brief introduction to the first IANR section. PMID- 20350365 TI - Delayed outcome from surgically treated patients with benign nerve associated tumors of the extremities larger than 5 cm. AB - BACKGROUND: The purpose of this work was to analyse the surgical procedure used and the outcome from patients with solitary nerve associated benign tumors of the extremities (SNABTE) >5 cm. METHODS: A 15 year review was performed for all patients with SNABTE treated in our department. The surgical procedures used (complete or incomplete tumor removal, with or without nerve preservation), the needs for grafting techniques as well as the outcome were analysed. RESULTS: Nine (9.5%) of 94 patients with SNABTE met the study requirements. The histological diagnosis revealed a schwannoma in four cases, a neurofibroma in three cases, one lipoma and one lipofibroma. Seven lesions could be completely excised. Preservation of the nerve bundles with complete neurological recovery was possible in five cases. The resection of a 22 cm neurofibroma without preservation of the nerve did not add measurable residual neurological deficits. One patient with a peroneal neurofibroma required a grafting procedure. Intentional incomplete tumor excisions were performed in two patients with well preserved nerve functions where a median nerve lipofibroma and a radial nerve neurofibroma were diagnosed. All patients showed different degrees of improved outcome. CONCLUSIONS: We conclude that the complete resection of large SNABTE, excepting lipofibromas and some neurofibromas, is always possible and associated with an improved outcome. The nerve preservation should be attempted in all cases, particularly in those with conserved functionality of a major nerve trunk. PMID- 20350366 TI - Cilostazol attenuates cerebral vasospasm after experimental subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, is a peripheral vasodilator, an anti inflammatory, and causes antiplatelet aggregation. We investigated these effects on cerebral vasospasm after rat SAH. METHODS: Thirty-eight Sprague-Dawley rats were randomly divided into three groups: SAH + normal feed (SAH group; n=14), SAH + feed containing 0.1% cilostazol (cilostazol group; n=12) and sham-operated rats (sham group; n=12). The basilar arteries (BA) of all groups were analysed by measuring wall thickness, internal luminal perimeter and cross-sectional area on day 7. Immunohistochemical study with RM-4, an anti-rat macrophage/dendritic cells monoclonal antibody and ultrastructural study with transmission electron microscopy were performed. RESULTS: Although most animals in the SAH group presented with typical vasospasm, the means of inner perimeter and cross-section area of the BA in the cilostazol group were significantly greater than the SAH group (836 +/- 134 MUm versus 771 +/- 125 MUm and 39 177 +/- 15 405 MUm(2) versus 33 098 +/- 13 871 MUm(2), respectively). Wall thickness of the BA in the cilostazol group demonstrated significant decrease, compared with the SAH group (17.4 +/- 2.3 versus 21.0 +/- 2.7 MUm). In immunohistological study, SAH induced an obvious increase in mean perivascular RM-4-positive cell count, whereas cilostazol significantly reduced it by 59%. Ultrastructural study depicted cilostazol markedly attenuating structural deterioration of the vascular wall due to SAH. CONCLUSIONS: This work demonstrates that cilostazol attenuates cerebral vasospasm after SAH in rat, possibly in part due to the anti inflammatory effect. PMID- 20350367 TI - PPARgamma agonist rosiglitazone is neuroprotective after traumatic spinal cord injury via anti-inflammatory in adult rats. AB - Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARgamma which is shown to induce neuroprotection in animal models of focal ischemia and traumatic brain injury. SCI is induced by the application of vascular clips (force of 24 g) to the dura via a four-level T(5)-T(8) laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of rosiglitazone, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) apoptosis (terminal deoxynucleotidyl transferase mediated UTP end labeling staining and electron microscopy); (4) proinflammatory cytokines TNF-alpha and IL-beta; (5) PPARgamma, HSP70 and HSP27 expressions. To elucidate whether the protective effects of rosiglitazone were mediated via the estrogen receptors, we investigated the effect of a PPARgamma antagonist, GW9662, on the protective effects of rosiglitazone. GW9662 significantly antagonized the effect of the rosiglitazone and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of rosiglitazone after SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma. PMID- 20350368 TI - Diagnosis and management of Rosai-Dorfman disease involving the central nervous system. AB - INTRODUCTION: Rosai-Dorfman disease is a benign non-neoplastic proliferative disorder of histiocytes originally described in the cervical lymph nodes. Extranodal sites were later recognized, and by 1990, they were shown to represent over 40% of cases; however, central nervous system involvement is still considered rare. We review the literature, which shows a steady increase in reports of Rosai-Dorfman disease involving the brain and/or spine. METHODS: A literature search was performed for the period 1969-2008, using multiple search engines, with keywords Rosai-Dorfman disease, central nervous system Rosai Dorfman disease and sinus histiocytosis with massive lymphadenopathy. RESULTS: By December 2008, 111 cases of Rosai-Dorfman disease involving the central nervous system had been reported in the literature, including our cases. In the central nervous system, Rosai-Dorfman disease is ubiquitous. Although it is characterized by unique, indeed pathognomonic, histopathological cytoarchitecture, it may be mistaken for many other neoplastic and inflammatory histioproliferative diseases. Surgical resection with post-operative corticosteroids remains the treatment of choice. CONCLUSIONS: Rosai-Dorfman disease involving the central nervous system appears to be more common than previously thought and may well assume a more prominent place in the differential diagnoses of dural-based lesions. Expert awareness of the characteristic histopathology and immunohistochemistry of the disease is required for accurate diagnosis. PMID- 20350369 TI - Factors influencing emerging infectious diseases in the southeastern United States. PMID- 20350370 TI - Findings, gaps, and future direction for research in nonpharmaceutical interventions for pandemic influenza. PMID- 20350371 TI - Livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 in humans, Canada. AB - Rates of colonization with livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) sequence type 398 have been high for pigs and pig farmers in Canada, but prevalence rates for the general human population are unknown. In this study, 5 LA-MRSA isolates, 4 of which were obtained from skin and soft tissue infections, were identified from 3,687 tested MRSA isolates from persons in Manitoba and Saskatchewan, Canada. Further molecular characterization determined that these isolates all contained staphylococcal cassette chromosome (SCC) mecV, were negative for Panton-Valentine leukocidin, and were closely related by macrorestriction analysis with the restriction enzyme Cfr91. The complete DNA sequence of the SCCmec region from the isolate showed a novel subtype of SCCmecV harboring clustered regularly interspaced short palindromic repeats and associated genes. Although prevalence of livestock-associated MRSA seems to be low for the general population in Canada, recent emergence of infections resulting from this strain is of public health concern. PMID- 20350372 TI - Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 subtype infections of mice. AB - To determine if fatal infections caused by different highly virulent influenza A viruses share the same pathogenesis, we compared 2 different influenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathogenicity in laboratory mice, were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, each had a distinct pathologic signature and caused a different course of acute respiratory distress syndrome. In the absence of any virus labeling, a histologist could readily distinguish infections caused by these 2 viruses. The different histologic features described in this study here refute the hypothesis of a single, universal cytokine storm underlying all fatal influenza diseases. Research is thus crucially needed to identify sets of virulence markers and to examine whether treatment should be tailored to the influenza virus pathotype. PMID- 20350373 TI - Clostridium difficile infections among hospitalized children, United States, 1997 2006. AB - We evaluated the annual rate (cases/10,000 hospitalizations) of pediatric hospitalizations with Clostridium difficile infection (CDI; International Classification of Diseases, 9th revision, clinical modification code 008.45) in the United States. We performed a time-series analysis of data from the Kids' Inpatient Database within the Health Care Cost and Utilization Project during 1997-2006 and a cross-sectional analysis within the National Hospital Discharge Survey during 2006. The rate of pediatric CDI-related hospitalizations increased from 7.24 to 12.80 from 1997 through 2006; the lowest rate was for children <1 year of age. Although incidence was lowest for newborns (0.5), incidence for children <1 year of age who were not newborns (32.01) was similar to that for children 5-9 years of age (35.27), which in turn was second only to incidence for children 1-4 years of age (44.87). Pediatric CDI-related hospitalizations are increasing. A better understanding of the epidemiology and outcomes of CDI is urgently needed. PMID- 20350374 TI - Phylogenetic analysis of enterohemorrhagic Escherichia coli O157, Germany, 1987 2008. AB - Multilocus variable number tandem repeat analysis (MLVA) is a subtyping technique for characterizing human pathogenic bacteria such as enterohemorrhagic Escherichia coli (EHEC) O157. We determined the phylogeny of 202 epidemiologically unrelated EHEC O157:H7/H- clinical isolates through 8 MLVA loci obtained in Germany during 1987-2008. Biodiversity in the loci ranged from 0.66 to 0.90. Four of 8 loci showed null alleles and a frequency < or =44.1%. These loci were distributed among 48.5% of all strains. Overall, 141 MLVA profiles were identified. Phylogenetic analysis assigned 67.3% of the strains to 19 MLVA clusters. Specific MLVA profiles with an evolutionary persistence were identified, particularly within sorbitol-fermenting EHEC O157:H-.These pathogens belonged to the same MLVA cluster. Our findings indicate successful persistence of this clone. PMID- 20350375 TI - Use of norovirus genotype profiles to differentiate origins of foodborne outbreaks. AB - Because secondary transmission masks the connection between sources and outbreaks, estimating the proportion of foodborne norovirus infections is difficult. We studied whether norovirus genotype frequency distributions (genotype profiles) can enhance detection of the sources of foodborne outbreaks. Control measures differ substantially; therefore, differentiating this transmission mode from person-borne or food handler-borne outbreaks is of public health interest. Comparison of bivalve mollusks collected during monitoring (n = 295) and outbreak surveillance strains (n = 2,858) showed 2 distinguishable genotype profiles in 1) human feces and 2) source-contaminated food and bivalve mollusks; genotypes I.2 and I.4 were more frequently detected in foodborne outbreaks. Overall, approximately 21% of all outbreaks were foodborne; further analysis showed that 25% of the outbreaks reported as food handler-associated were probably caused by source contamination of the food. PMID- 20350377 TI - Household transmission of pandemic (H1N1) 2009, San Antonio, Texas, USA, April May 2009. AB - To assess household transmission of pandemic (H1N1) 2009 in San Antonio, Texas, USA, during April 15-May 8, 2009, we investigated 77 households. The index case patient was defined as the household member with the earliest onset date of symptoms of acute respiratory infection (ARI), influenza-like illness (ILI), or laboratory-confirmed pandemic (H1N1) 2009. Median interval between illness onset in index and secondary case-patients was 4 days (range 1-9 days); the index case patient was likely to be < or =18 years of age (p = 0.034). The secondary attack rate was 4% for pandemic (H1N1) 2009, 9% for ILI, and 13% for ARI. The secondary attack rate was highest for children <5 years of age (8%-19%) and lowest for adults > or =50 years of age (4%-12%). Early in the outbreak, household transmission primarily occurred from children to other household members and was lower than the transmission rate for seasonal influenza. PMID- 20350376 TI - Reassortment of human rotavirus gene segments into G11 rotavirus strains. AB - G11 rotaviruses are believed to be of porcine origin. However, a limited number of G11 rotaviruses have been recently isolated from humans in combination with P[25], P[8], P[6], and P[4]. To investigate the evolutionary relationships of these strains, we analyzed the complete genomes of 2 human G11P[25] strains, 2 human G11P[8] strains, and 3 porcine reference strains. Most of the 11 gene segments of these 7 strains belonged to genotype 1 (Wa-like). However, phylogenetic clustering patterns suggested that an unknown G11P[25] strain with a new I12 VP6 genotype was transmitted to the human population, in which it acquired human genotype 1 gene segments through reassortment, resulting in a human G11P[8] rotavirus strain with an entire human Wa-genogroup backbone. This Wa-like backbone is believed to have caused the worldwide spread of human G9 and G12 rotaviruses. G11 human rotavirus strains should be monitored because they may also become major human pathogens. PMID- 20350378 TI - Escherichia albertii in wild and domestic birds. AB - Escherichia albertii has been associated with diarrhea in humans but not with disease or infection in animals. However, in December 2004, E. albertii was found, by biochemical and genetic methods, to be the probable cause of death for redpoll finches (Carduelis flammea) in Alaska. Subsequent investigation found this organism in dead and subclinically infected birds of other species from North America and Australia. Isolates from dead finches in Scotland, previously identified as Escherichia coli O86:K61, also were shown to be E. albertii. Similar to the isolates from humans, E. albertii isolates from birds possessed intimin (eae) and cytolethal distending toxin (cdtB) genes but lacked Shiga toxin (stx) genes. Genetic analysis of eae and cdtB sequences, multilocus sequence typing, and pulsed-field gel electrophoresis patterns showed that the E. albertii strains from birds are heterogeneous but similar to isolates that cause disease in humans. PMID- 20350381 TI - Alfred Russel Wallace and the antivaccination movement in Victorian England. AB - Alfred Russel Wallace, eminent naturalist and codiscoverer of the principle of natural selection, was a major participant in the antivaccination campaigns in late 19th-century England. Wallace combined social reformism and quantitative arguments to undermine the claims of provaccinationists and had a major impact on the debate. A brief account of Wallace's background, his role in the campaign, and a summary of his quantitative arguments leads to the conclusion that it is unwarranted to portray Victorian antivaccination campaigners in general as irrational and antiscience. Public health policy can benefit from history, but the proper context of the evidence used should always be kept in mind. PMID- 20350379 TI - Community-associated methicillin-resistant Staphylococcus aureus strains in pediatric intensive care unit. AB - Virulent community-associated methicillin-resistant Staphylococcus-aureus (CA MRSA) strains have spread rapidly in the United States. To characterize the degree to which CA-MRSA strains are imported into and transmitted in pediatric intensive care units (PICU), we performed a retrospective study of children admitted to The Johns Hopkins Hospital PICU, March 1, 2007-May 31, 2008. We found that 72 (6%) of 1,674 PICU patients were colonized with MRSA. MRSA-colonized patients were more likely to be younger (median age 3 years vs. 5 years; p = 0.02) and African American (p<0.001) and to have been hospitalized within 12 months (p<0.001) than were noncolonized patients. MRSA isolates from 66 (92%) colonized patients were fingerprinted; 40 (61%) were genotypically CA-MRSA strains. CA-MRSA strains were isolated from 50% of patients who became colonized with MRSA and caused the only hospital-acquired MRSA catheter-associated bloodstream infection in the cohort. Epidemic CA-MRSA strains are becoming endemic to PICUs, can be transmitted to hospitalized children, and can cause invasive hospital-acquired infections. Further appraisal of MRSA control is needed. PMID- 20350380 TI - Contribution of Streptococcus anginosus to infections caused by groups C and G streptococci, southern India. AB - Vellore, a region in southern India, has a high incidence of severe human infections with Beta-hemolytic group C and G streptococci (GCGS). To determine the causative species in these infections, we conducted 16S rRNA gene sequencing: Streptococcus dysgalactiae subsp. equisimilis (81%) and S. anginosus (19%) were the causative organisms in the 2-year study period (2006-2007). We used PCR to detect the virulence-related emm gene; results showed that it was restricted to S. dysgalactieae subsp. equisimilis isolates of 99.2% tested positive. Due to a novel marker, S. anginosus and S. constellatus can be quickly and accurately distinguished from other members of the genus. The notable contribution of the anginosus group to human infections suggests that this group of obligate pathogens deserves more attention in healthcare and research. PMID- 20350382 TI - Innovative uses for syndromic surveillance. AB - To determine if expanded queries can be used to identify specific reportable diseases/conditions not detected by using automated syndrome categories, we developed new categories to use with the Electronic Surveillance System for the Early Notification of Community Based Epidemics. Results suggest innovative queries can enhance clinicians' compliance with reportable disease requirements. PMID- 20350383 TI - Plasmodium knowlesi in human, Indonesian Borneo. AB - Plasmodium knowlesi is now established as the fifth Plasmodium species to cause malaria in humans. We describe a case of P. knowlesi infection acquired in Indonesian Borneo that was imported into Australia. Clinicians need to consider this diagnosis in a patient who has acquired malaria in forest areas of Southeast Asia. PMID- 20350385 TI - Fluoroquinolone resistance and Clostridium difficile, Germany. AB - We characterized 670 Clostridium difficile isolates collected from patients in 84 hospitals in Germany in 2008. PCR ribotyping showed high prevalence of ribotype 001 and restricted dissemination of ribotype 027 strains. Fluoroquinolone resistance and associated gyrase mutations were frequent in various ribotypes, but no resistance to metronidazole or vancomycin was noted. PMID- 20350386 TI - Hypervirulent Clostridium difficile strains in hospitalized patients, Canada. AB - To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004 2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008. PMID- 20350387 TI - Porcine-origin gentamicin-resistant Enterococcus faecalis in humans, Denmark. AB - During 2001-2002, high-level gentamicin-resistant (HLGR) Enterococcus faecalis isolates were detected in 2 patients in Denmark who had infective endocarditis and in pigs and pork. Our results demonstrate that these isolates belong to the same clonal group, which suggests that pigs are a source of HLGR E. faecalis infection in humans. PMID- 20350388 TI - Merkel cell polyomavirus in cutaneous swabs. AB - To assess the usefulness of using cutaneous swabs to detect Merkel cell polyomavirus (MCPyV) DNA, we analyzed swabs from persons with Merkel cell carcinoma (MCC), others with skin diseases, and healthy volunteers. MCPyV was detected in at least 1 sample from virtually all participants. Viral loads were higher in samples from patients with MCC. PMID- 20350389 TI - Novel Corynebacterium diphtheriae in domestic cats. AB - Novel nontoxigenic Corynebacterium diphtheriae was isolated from a domestic cat with severe otitis. Contact investigation and carrier study of human and animal contacts yielded 3 additional, identical isolates from cats, although no evidence of zoonotic transmission was identified. Molecular methods distinguished the feline isolates from known C. diphtheriae. PMID- 20350390 TI - Sympatric occurrence of 3 arenaviruses, Tanzania. AB - To determine the specificity of Morogoro virus for its reservoir host, we studied its host range and genetic diversity in Tanzania. We found that 2 rodent species other than Mastomys natalensis mice carry arenaviruses. Analysis of 340 nt of the viral RNA polymerase gene showed sympatric occurrence of 3 distinct arenaviruses. PMID- 20350391 TI - Evolution of porcine kobuvirus infection, Hungary. AB - Porcine kobuvirus was first identified in early 2007 in Hungary. Originally thought to be confined to the intestine, almost 2 years later the virus was found in the blood of clinically healthy pigs on the same farm. Porcine kobuvirus may be widely distributed on pig farms worldwide. PMID- 20350392 TI - Influenza virus transmission from horses to dogs, Australia. AB - During the 2007 equine influenza outbreak in Australia, respiratory disease in dogs in close contact with infected horses was noted; influenza (H3N8) virus infection was confirmed. Nucleotide sequence of the virus from dogs was identical to that from horses. No evidence of dog-to-dog transmission or virus persistence in dogs was found. PMID- 20350393 TI - Limited susceptibility of chickens, turkeys, and mice to pandemic (H1N1) 2009 virus. AB - To determine susceptibility of chickens, turkeys, and mice to pandemic (H1N1) 2009 virus, we conducted contact exposure and inoculation experiments. We demonstrated that chickens were refractory to infection. However, oculo oronasally inoculated turkeys and intranasally inoculated mice seroconverted without clinical signs of infection. PMID- 20350394 TI - Pandemic (H1N1) 2009 infection in swine herds, Manitoba, Canada. AB - In Manitoba, Canada, several swine herds were infected by pandemic (H1N1) 2009 virus in the summer of 2009. Results of several investigations concluded that outbreaks of infection with this virus are similar in duration to outbreaks of infections with swine influenza viruses A (H1N1) and A (H3N2). PMID- 20350395 TI - Pandemic (H1N1) 2009 in breeding turkeys, Valparaiso, Chile. AB - Pandemic (H1N1) 2009 virus was detected in breeding turkeys on 2 farms in Valparaiso, Chile. Infection was associated with measurable declines in egg production and shell quality. Although the source of infection is not yet known, the outbreak was controlled, and the virus was eliminated from the birds. PMID- 20350396 TI - 16S rRNA methyltransferase RmtC in Salmonella enterica serovar Virchow. AB - We screened Salmonella and Escherichia coli isolates, collected 2004-2008 in the United Kingdom, for 16S rRNA methyltransferases. rmtC was identified in S. enterica serovar Virchow isolates from clinical samples and food. All isolates were clonally related and bore the rmtC gene on the bacterial chromosome. Surveillance for and research on these resistance determinants are essential. PMID- 20350397 TI - Reemergence of dengue in Mauritius. AB - Dengue reemerged in Mauritius in 2009 after an absence of >30 years, and >200 cases were confirmed serologically. Molecular studies showed that the outbreak was caused by dengue virus type 2. Phylogenetic analysis of the envelope gene identified 2 clades of the virus. No case of hemorrhagic fever was recorded. PMID- 20350398 TI - Pandemic (H1N1) 2009 risk for nurses after trivalent vaccination. PMID- 20350399 TI - One flu for One Health. PMID- 20350400 TI - Patients with pandemic (H1N1) 2009 in intensive care units, Israel. PMID- 20350401 TI - Risk for transmission of pandemic (H1N1) 2009 virus by blood transfusion. PMID- 20350402 TI - Rapid emergence of oseltamivir resistance. PMID- 20350403 TI - Dual seasonal patterns for influenza, China. PMID- 20350404 TI - Avian influenza prevalence in pigs, Egypt. PMID- 20350406 TI - Ventilator-associated pneumonia and MRSA ST398, Italy. PMID- 20350405 TI - Triple reassortant swine influenza A (H3N2) virus in waterfowl. PMID- 20350407 TI - Panton-Valentine leukocidin-positive MRSA, Shanghai. PMID- 20350408 TI - Clostridium difficile in ground meat, France. PMID- 20350409 TI - WUPyV in children with acute respiratory tract infections, China. PMID- 20350410 TI - Intestinal capillariasis, western Mindanao, the Philippines. PMID- 20350411 TI - Buruli ulcer lesions in HIV-positive patient. PMID- 20350412 TI - Hantavirus pulmonary syndrome, French Guiana. PMID- 20350413 TI - Fatal human case of West Nile disease, Mexico, 2009. PMID- 20350414 TI - Bartonella spp. infections, Thailand. PMID- 20350415 TI - Cholera outbreak, Laos, 2007. PMID- 20350416 TI - Buruli ulcer, Central African Republic. PMID- 20350420 TI - [Lipoprotein lipase gene mutations and the risk of cardiovascular diseases in children with obesity]. AB - OBJECTIVE: To inquire into the relationship between lipoprotein lipase (LPL) gene D9N, N291S and S447X polymorphisms and the development of cardiovascular diseases in children with obesity. METHODS: The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RLFP) techniques were used to detect three common mutations of LPL gene exon D9N, N291S and S447X in 157 obese children and 175 normal controls. Plasma lipid and lipoprotein levels between children with different genotypes were compared. RESULTS: The D9N and N291S gene mutations were not detected in either the obese or the control groups. There were no significant differences in the frequency of S447X gene mutation between the two groups. There were no significant differences in the levels of plasma lipid and lipoprotein between children with S447 and X447 genotypes. CONCLUSIONS: D9N and N291S gene mutations may not be risk factors associated with cardiovascular diseases in children with obesity. S447X gene mutation might not play an important role in the development of cardiovascular diseases in childhood. PMID- 20350421 TI - [Diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy in children]. AB - OBJECTIVE: To summarize the experience in diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in children. METHODS: A total of 14 children (7 females and 7 males) with ARVC were involved. The cases underwent electrocardiography, echocardiography, cardiac CT or MRI examinations. All cases were treated with sotalol or amiodarone in combination with propranolol. In 2 cases with drug-refractory ventricular extrasystoles, catheter ablation treatment was performed. In 6 cases with obvious impaired ventricular function, additional pharmacological therapy including vasodilators, diuretics, and digitalis were given. RESULTS: Ventricular extrasystoles occurred in all 14 cases and ventricular tachycardia in 8 cases. Ten cases showed Epsilon wave on electrocardiography. All 14 cases had enlarged right ventricle and reduced right ventricular ejection fraction. CT or MRI examination showed right ventricular dilatation and a thinned wall of right ventricle in 10 cases. Ventricular extrasystoles or tachycardia disappeared in 7 cases and was reduced in 4 cases after treatment. The two children receiving catheter ablation treatment did not present ventricular extrasystoles or tachycardia in a 3-month follow-up. The heart function was improved in the 6 children with obvious impaired ventricular function after pharmacological therapy. CONCLUSIONS: The clinical manifestations are diverse in children with ARVC. A definite diagnosis of ARVC should be based on a combination of electrocardiography and echocardiography examinations. Pharmacological therapy is effective partially. Catheter ablation treatment appears to be a promising option in patients with drug-refractory ventricular extrasystoles. PMID- 20350422 TI - [Levels of serum brain natriuretic peptide and the correlation to heart function in children with Kawasaki disease]. AB - OBJECTIVE: To study serum levels of brain natriuretic peptide (BNP) in children with Kawasaki disease (KD) and the correlation between BNP levels and the heart function. METHODS: Forty-three children with KD and thirty healthy children were enrolled. Serum levels of BNP were measured using ELISA. KD children received an echocardiographic examination, including measurements of left ventricular ejection fraction (LVEF), left ventricular shorten fraction (LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus. RESULTS: Mean serum level of BNP at the acute stage in children with KD was significantly higher than that at the recovery stage as well as the control group (p<0.01). The LVEF, LVSF and CI levels at the acute stage were significantly lower than those at the recovery stage in children with KD (p<0.05). The linear regression analysis showed that the BNP level was negatively correlated with the levels of LVEF, LVSF and CI (r=-0.63, -0.52, -0.53, p<0.05). CONCLUSIONS: The serum BNP levels increase significantly in KD children at the acute stage, and are negatively correlated with the levels of LVEF, LVSF and CI. Measurement of serum BNP level is useful for the early diagnosis of KD. PMID- 20350423 TI - [Clinical characteristics of children with B cell type acute lymphoblastic leukemia carrying different fusion gene]. AB - OBJECTIVE: To investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes. METHODS: The research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009. RESULTS: In the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now. CONCLUSIONS: The B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis. PMID- 20350424 TI - [Expression of CREB/Bcl-2 in bone marrow mononuclear cells of children with acute leukemia]. AB - OBJECTIVE: To study the expression and role of cyclic-AMP response binding protein (CREB) and Bcl-2 in children with acute leukemia. METHODS: Ninety-two children with acute leukemia (leukemia group) and 30 children with non hematologic malignancies (control group) were enrolled. The mRNA and protein expression of CREB and Bcl-2 in bone marrow mononuclear cells were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot. RESULTS: The mRNA and protein expression of CREB and Bcl-2 in the leukemia group was significantly higher than that in the control group (p<0.01). There were no significant differences in the expression of CREB and Bcl-2 between acute lymphoblastic leukemia and acute myeloid leukemia subgroups. At the initial diagnosis, the mRNA and protein expression of CREB and Bcl-2 in children with extramedullary infiltration was higher than that in children without (p<0.05). In the leukemia group, the mRNA and protein expression of CREB and Bcl-2 in the complete remission subgroup was significantly lower than that in the non-complete remission subgroup (p<0.01). High mRNA expression of CREB and Bcl-2 in the leukemia group was positively correlated with peripheral blood leucocyte counts (r=0.62, 0.71 respectively, p<0.05). There was a positive correlation between mRNA and protein expression of CREB and Bcl-2 (r=0.75, 0.68 respectively; p<0.05). CONCLUSIONS: The expression of CREB and Bcl-2 may be correlated with the pathogenesis and clinical prognosis of childhood leukemia, however, their expression may not be associated with the classification of acute leukemia. PMID- 20350425 TI - [Detection of ICAM-1 and RANTES in infants with bronchiolitis]. AB - OBJECTIVE: To explore the role of intercellular adhesion molecule-1 (ICAM-1) and regulated upon activation normal T cell expressed and secreted (RANTES) in bronchiolitis and their correlation in the pathogenesis of this disorder. METHODS: The expression of ICAM-1 was detected by flow cytometry on lymphocytes of peripheral blood in 28 infants with bronchiolitis, 23 infants with bronchopneumonia and 24 healthy infants. Serum level of RANTES was assayed using ELISA. The correlation between ICAM-1 and RANTES levels was evaluated using Pearson correlation coefficient. RESULTS: The ICAM-1 level in the bronchiolitis group (35.0+/-10.3%) was much higher than that in the bronchopneumonia (29.9+/ 8.6%; p<0.05) and the control groups (24.6+/-6.9%; p<0.01). The bronchopneumonia group had higher ICAM-1 level than the control group (p<0.05). The RANTES level in the bronchiolitis (32.1+/-6.0 ng/mL) and the bronchopneumonia groups (30.6+/ 6.2 ng/mL) was significantly higher than that in the control group (27.1+/-5.1 ng/mL) (p<0.01, p<0.05, respectively), however, no significant difference was found between the bronchopneumonia and bronchiolitis groups. There was a positive correlation between ICAM-1 and RANTES levels in the bronchiolitis group (r=0.675, P<0.01). CONCLUSIONS: ICAM-1 and RANTES are involved in the pathogenesis of bronchiolitis and show a synergistic effect. PMID- 20350426 TI - [Microbiological etiology in children with community acquired pneumonia]. AB - OBJECTIVE: To study the distribution of pathogenic microorganisms of community acquired pneumonia (CAP) in children. METHODS: Respiratory secretion and blood specimens were collected in 1167 children with CAP within 4 hrs of admission. Mycoplasma pneumonia and Chlamydia trachomatis were detected by RT-PCR in respiratory secretion specimens. Respiratory syncytial virus (RSV-IgM) and Adenovirus (ADV-IgM) were tested using ELISA in blood samples. RESULTS: A total of 308 strains of bacteria were isolated from the respiratory tract secretions, with gram positive strains of 53.6% and gram negative strains of 46.4%. The top five bacteria strains detected were Streptococcus pneumoniae (35.1%), Escherichia coli (11.7%), Staphylococcus aureus (8.8%), Klebsiella pneumonia (6.5%) and Moraxelle catarrhalis (5.8%) in turn. Beta-lactamase and ESBLs producing strains accounted for 30.1% in the top five bacteria strains. The non-bacteria pathogens were found in 281 specimens (24.1%). Respiratory syncytial virus accounted for the most prevalent pathogen (19.3%). The mixed infection of respiratory syncytial virus and Streptococcus pneumoniae was common (35.2%). The infection rate from most of pathogenic microorganisms among children under the age of one was higher than that in children over one year old. CONCLUSIONS: Respiratory syncytial virus and Streptococcus pneumoniae are the major pathogens of CAP in children. The risk of pathogenic microorganism infections in children under the age of one is higher than that of children over one year old. PMID- 20350427 TI - [Clinical and pathological features of Alport syndrome in children]. AB - OBJECTIVE: To study the clinical and pathological features of Alport syndrome in children. METHODS: The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. RESULTS: There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. CONCLUSIONS: The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome. PMID- 20350428 TI - [Effects of probiotics on intestinal bacterial colonization in premature infants]. AB - OBJECTIVE: To study the possible roles of probiotics in decreasing intestinal bacterial colonization rate and the incidence of enterogenic infections in premature infants. METHODS: Seventy premature infants were randomly assigned to two groups: probiotics and conventional treatment groups (control) (n=35 each). The probiotics treatment group was administered with oral Clostridium butyricum powder (250 mg, twice daily up to discharge) 24 hrs after birth except conventional treatment. Rectal swab cultures were done at admission, 5 and 12 days after admission, and before discharge. Clinical and laboratory findings were compared between the two groups. RESULTS: The intestinal bacterial colonization rate in the probiotics treatment group was lower than that in the control group 12 days after admission (60% vs 83%; p<0.05) and before discharge (51% vs 80%; p<0.05). Klebsiella pneumoniae, Escherichia coli and Enterococcus faecium were common colonization bacteria in the two groups. Diarrhea occurred in 7 cases (20%) in the probiotics treatment group compared with 16 cases (46%) in the control group (p<0.05). Two infants (6%) developed sepsis in the probiotics treatment group compared with 9 cases (26%) in the control group (p<0.05). CONCLUSIONS: Probiotics can decrease intestinal bacterial colonization rate and the incidence of diarrhea and sepsis in premature infants. PMID- 20350429 TI - [Application of endotracheal lavage in neonatal ventilator-associated pneumonia]. AB - OBJECTIVE: To study the efficacy of endotracheal lavage in neonatal ventilator associated pneumonia (VAP). METHODS: Fifty-eight neonates with VAP between January 2002 and December 2008 were randomly assigned to two groups: lavage and control (n=29 each). After withdrawal from ventilator, both groups received sensitive antibiotics therapy according to sputum culture results as well as supportive treatment. The lavage group was additionally treated with endotracheal lavage (2-3 times daily). The therapeutic effects were compared between the two groups. RESULTS: There were no significant differences in the average time of mechanical ventilation between the lavage and the control groups. The effective rate in the lavage group (93%) was significantly higher than that in the control group (69%; p<0.05). Three percent of patients in the lavage group required twice or more mechanical ventilation compared with 24% in the control group (p<0.05). Blood gas analysis results were obviously improved in the lavage group 2 hrs after treatment (p<0.01). CONCLUSIONS: Endotracheal lavage can decrease the number in mechanical ventilation and improve therapeutic effects in neonates with VAP. PMID- 20350430 TI - [Comparison of therapeutic effects in severe nocturia: gradual versus immediate drug withdrawal]. AB - OBJECTIVE: To investigate possible differences in the prognosis in children with severe nocturia who received different drug withdrawal schedules. METHODS: Ninety seven children with severe nocturia were randomly assigned to two groups: control (n=47) and observed (n=50). The control group accepted drug withdrawal immediately, while the observed group accepted dose tapering gradually after a 12 week treatment course. The frequency of enuresis was observed three months after complete drug withdrawal. RESULTS: During the treatment, the frequency of enuresis in all of children from both the control and the observed groups was reduced by over 90%. Forty-six children (92%) from the observed group showed the frequency of enuresis was reduced by over 90%, but 28 children (60%) from the control group (p<0.01) three months after the complete drug withdrawal. There were no significant differences in the adverse effect and the medication compliance between the two groups. CONCLUSIONS: The different schedules of drug withdrawal may lead to different prognosis, and the schedule of gradual drug withdrawal may be superior to the immediate one in children with nocturnal enuresis. PMID- 20350431 TI - [NMDAR expression in the cochlear nucleus and hearing damage in neonatal rats with hyperbilirubinemia]. AB - OBJECTIVE: To study the role of N-methyl-D-aspartate-receptor (NMDAR) expression in the development of hearing damage in neonatal rats with hyperbilirubinemia. METHODS: Sixty seven-day-old Sprague-Dawley rats were randomly injected with bilirubin of 100 microg/g (low-dose treatment group) or 200 microg/g (high-dose treatment group) or normal saline (control group). Auditory brainstem response (ABR) was examined. The concentrations of bilirubin in blood and brain were measured. NMDAR expression in the cochlear nucleus slices was examined by immunohistochemistry assay. RESULTS: ABR reflecting threshold obviously increased, and I, II and III wave latency as well as I-II, II-III and I-III interval were more prolonged in the two bilirubin treatment groups when compared with the control group. The NMDAR expression in the cochlear nucleuse in the two bilirubin treatment groups was obviously lower than that in the control group. The NMDAR expression in the cochlear nucleuse was negatively correlated with the brain bilirubin content and the ABR reflecting threshold in the two bilirubin treatment groups. CONCLUSIONS: An increased NMDAR activity may play an important role in hearing damage following hyperbilirubinemia. PMID- 20350432 TI - [Protection of edaravone on neurons and its effects on the expression of interleukin-lbeta in juvenile rat hippocampus following status convulsion]. AB - OBJECTIVE: To study the possible protection of edaravone on neurons of the hippocampus after status convulsion (SC) and its effects on the expression of interleukin-1beta (IL-lbeta) in juvenile rats. METHODS: One hundred and ninety five juvenile male Sprague-Dawley rats were randomly divided into three groups: SC, edaravone pretreatment and normal saline control (control group). Each group was subdivided into five groups sacrificed at 4, 12, 24, 48 and 72 hrs after SC induction. SC model was prepared using lithium-pilocarpine. The edaravone pretreatment group received edaravone by intraperitoneal injection once daily three days before convulsion induction. Histopathologic changes in the hippocampus were viewed under a light microscope and an electron microscope. Expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL). Expression of IL-lbeta protein was determined by immunohistochemistry. RESULTS: Under the electron microscrope, a small quantity of neurons showed karyopycnosis and endocytoplasmic reticulum (ER) expanded remarkably 24 hrs after SC induction; at 48 hrs the ER expanding was alleviated somewhat but mitochomdria swelling was more severe. The edaravone pretreatment group showed less severe neuronal changes compared with the SC group under the microscopes. The TUNEL positive cells in the hippocampus of the SC group were significantly more than those of the control group 12 hrs, and peaked at 48 hrs after SC induction. The edaravone pretreatment group showed decreased TUNEL positive cells in the hippocampus compared with the SC group, although the positive cells were more than those in the control group between 12 and 48 hrs after SC induction. The immunohistochemistry assay demonstrated that the expression of IL-lbeta in the hippocampus of the SC group increased significantly compared with that of the control group 12, 24, 48 and 72 hrs after SC induction. Edaravone pretreatment resulted in a significantly decreased IL-lbeta expression in the hippocampus as compared with the SC group. CONCLUSIONS: Edaravone pretreatment may decrease the IL-1beta expression and neuronal apoptosis in the hippocampus. This suggests that edaravone may have protective effects against the hippocampal damage caused by SC. PMID- 20350433 TI - [Effect of magnesium-free on glucocorticoid receptor expression in primary cultured cortical neurons of fetal rats in vitro]. AB - OBJECTIVE: To study the changes of glucocorticoid receptor (GR) expression in embryonic rat cortical neurons exposed to transient Mg(2+)-free treatment. METHODS: Six days after rat cortical neuronal cultures, two groups were created based on the medium to which were transiently exposed. The control group was exposed to a physiological solution (PS), and the Mg(2+)-free group was exposed to the same medium as the control group except for the removal of magnesium. The expression of GR mRNA and protein was determined by real-time PCR and immunocytochemistry staining 1, 7 and 12 days after transient Mg(2+)-free treatment. RESULTS: Compared to the control group, the Mg(2+)-free group displayed the significantly less accumulated optical density (AOD) of GR immunoreactivity 12 days after transient Mg(2+)-free treatment (p<0.05). On the contrary, GR mRNA expression increased significantly 1 and 7 days after transient Mg(2+)-free treatment in the Mg(2+)-free group (p<0.05). CONCLUSIONS: GR expression is modified following Mg-free-induced injury in cultured developing neurons in rats. PMID- 20350434 TI - [Expression of stromal cell derived factor-1 and CXC chemokine receptor 4 and the effects of budesonide on their expression in mice with asthma]. AB - OBJECTIVE: To study the expression of stromal cell derived factor-1(SDF-1) and CXC chemokine receptor 4 (CXCR4) in the airway and the effect of budesonide on their expression in mice with asthma. METHODS: Thirty BALB/c male mices were randomly divided into three groups: placebo control, untreated asthma, and budesonide-treated asthma. The asthma group were induced by intraperitoneal injection of 10% ovalbumin (OVA ) on days 1, 8 and 15, and then from days 22 to 34, challenged by inhalation of 2% OVA aerosol every other day. The budesonide treated asthma group received an inhalation of budesonide (1 mg ) before OVA challenge. The pathological changes of the airway were assessed by hematoxylin and eosin staining. The immunohistochemistry was used to estimate the expression of SDF-1 in the lung. RT-PCR was used to evaluate the expression of CXCR4 in the lung. RESULTS: Compared with the control group, SDF-1 and CXCR4 expression in the lung in the untreated asthma group increased significantly (p<0.05). The budesonide-treated asthma group demonstrated significantly decreased SDF-1 (0.426+/-0.052 vs 0.361+/-0.065; p<0.05) and CXCR4 (0.829+/-0.027 vs 0.723+/ 0.094; p<0.05) expression in the lung as compared with the untreated asthma group. Both SDF-1 (r=0.744, p<0.01) and CXCR4 (r=0.553, p<0.01)were positively correlated with the thickness of the airway wall. CONCLUSIONS: SDF-1 and CXCR4 may be associated with airway remodeling in mice with asthma. Budesonide can improve airway remodeling, possibly by decreasing the expression of SDF-1 and CXCR4. PMID- 20350435 TI - [Expression of high mobility group protein-B1 in mice with hyperoxia-induced bronchopulmonary dysplasia]. AB - OBJECTIVE: To study the effect of hyperoxia exposure on high mobility group protein-B1 (HMGB1) expression in neonatal mice and the role of HMGB1 in the pathogenesis of bronchopulmonary dysplasia (BPD). METHODS: C57BL/6 mice were randomly exposed to 60% O2 or air 1 day after birth. BPD was induced by 60% O2 exposure. The pulmonary tissue samples were harvested 3, 7 and 14 days after exposure. The pathologic changes of pulmonary tissues were observed by hematoxylin and eosin staining, Masson staining and radical alveolar count. The expression of HMGB1 protein in lungs was detected by immunofluorescence. The expression of HMGB1 mRNA was detected by real-time fluorescent quantitative PCR. RESULTS: In the BPD group, the lungs developed decreased alceolar septation, swollen alveolar epithelium, stroma edema, interstitial fibrosis and developmental lag when compared with the control group. These changes became more obvious with more prolonged hyperoxia exposure. The expression of HMGB1 protein and mRNA 7 and 14 days after exposure increased significantly in the BPD group compared with that in the control group. CONCLUSIONS: Hyperoxia exposure results in an increase in lung HMGB1 expression. The increased HMGB1 expression may be associated with the development of BPD. PMID- 20350436 TI - [Prevalence of anemia in children between 3 and 6 years old from Huining, Gansu]. PMID- 20350437 TI - [Nasal continuous positive airway pressure for the treatment of severe pneumonia in children from the plateau area: clinical analysis of 47 cases]. PMID- 20350439 TI - [Application of bronchoscopy in 354 children]. PMID- 20350438 TI - [Clinical characteristics of children with Kawasaki disease complicated by coronary artery lesions]. PMID- 20350440 TI - [A case report of obesity hypoventilation syndrome]. PMID- 20350441 TI - [Misdiagnosis of disseminated cryptococcosis neoformens as histoplasmosis in a child]. PMID- 20350442 TI - [Vecuronium as an adjunct treatment for neonatal tetanus: case report of 2 cases]. PMID- 20350443 TI - [Related factors of insulin sensitivity in infants]. PMID- 20350445 TI - President's message. The earthquake in Haiti. PMID- 20350446 TI - Determinants of mammography use in rural and urban regions of Canada. AB - INTRODUCTION: National guidelines advocate biennial mammography screening for asymptomatic women aged 50-69 years. Unfortunately many women do not abide by such recommendations, and evidence indicates that compliance rates are lower in rural areas. METHODS: We estimated logistic regression models using data from the Canadian Community Health Survey for 2002/03 and 2004/05. We identified the extent of regional variation within and between Canadian provinces using a new and more detailed set of rural indicators based on economic zones of influence, after accounting for a range of demographic and socio-economic factors. RESULTS: The odds of asymptomatic women aged 50-69 years having undergone mammography during the previous 2 years were significantly lower for those residing in relatively remote and rural areas than for those residing in census metropolitan areas (odds ratio [OR] 0.58, confidence interval [CI] 0.42-0.80). This was also true of women residing in certain other rural areas that had some limited labour market attachment to larger urban areas (OR 0.81, CI 0.70-0.93), but there were no significant differences between smaller and larger urban areas. We also found variation in mammography use among women living in rural and urban areas across provinces. CONCLUSION: Mammography use is significantly lower in rural and remote areas, even after a range of other demographic and socio-economic factors are accounted for. One important factor underpinning this result appears to be differences in attitude about the importance of regular mammography screening between women residing in rural and urban areas. Information campaigns raising awareness about the importance of mammography screening should be targeted, in particular, at women residing in rural and remote areas. PMID- 20350447 TI - The experience of primary health care users: a rural-urban paradox. AB - INTRODUCTION: We sought to assess the care experience of primary health care users, to determine whether users' assessments of their experience vary according to the geographical context in which services are obtained, and to determine whether the observed variations are consistent across all components of the care experience. METHODS: We examined the experience of 3389 users of primary care in 5 administrative regions in Quebec, focusing on accessibility, continuity, responsiveness and reported use of health services. RESULTS: We found significant variations in users' assessments of the specific components of the care experience. Access to primary health care received positive evaluations least frequently, and continuity of information received the approval of the highest percentage of users. We also found significant variations among geographical contexts. Positive assessments of the care experience were more frequently made by users in remote rural settings; they became progressively less frequent in near-urban rural and near-urban settings, and were found least often in urban settings. We observed these differences in almost all of the components of the care experience. CONCLUSION: Given the relatively greater supply of services in urban areas, this analysis has revealed a rural-urban paradox in the care experience of primary health care users. PMID- 20350448 TI - Country cardiograms case 36. Right ventricular myocardial infarction. PMID- 20350449 TI - The occasional management of epistaxis. PMID- 20350451 TI - "Too many doctors"? PMID- 20350454 TI - [The Neuropad test in the screening of peripheral neuropathy in diabetic patients]. AB - One of the first signs of peripheral neuropathy is the loss of perspiration of the feet. Untill now, the Semmes-Weinstein monofilament test has been considered the gold test to detect early peripheral neuropathy. Recently, the Neuropad test has become available: it is a cobalt salt plaster designed to change colour from blue to pink in contact with liquids, namely sweating. The objective of this study was to find if the Neuropad test could be considered as a test for detecting peripheral autonomic neuropathy and to compare its sensitivity and specificity to the Semmes-Weinstein monofilament test. Forty diabetic patients were studied, 22 of them presented with peripheral neuropathy. The criteria used for the definition of neuropathy was based on the Neuropathy Disability Score (NDS). Under Semmes-Weinstein monofilament test, we found a sensitivity and specificity of 82% and 94%, respectively, and with the Neuropad test, a specificity of 44%, but a sensitivity of 100%. Ten patients presented a sudomotor dysfunction of the feet in the absence of peripheral neuropathy (based on the NDS criteria), and were considered as false positives. We concluded that the Neuropad test is a simple, sensitive test to screen for diabetic neuropathy. Based on the false positive results, we may consider it as a reliable test detecting neuropathy in a earlier phase. PMID- 20350455 TI - [Beliefs and attitudes of professionals about marital violence: studies with health professionals, policemen and teachers]. AB - This article presents a set of three research projects that aimed to characterize the beliefs about marital violence of the professionals most directly implied in the response and prevention of this problem. A research questionnaire that evaluates beliefs about marital violence was administered to a sample of 226 health professionals, 85 law enforcement agents and 280 teachers. On the global results show a tendency to moderate disagreement with beliefs that legitimize this form of abuse. Some myths, however, persist in these samples, namely those related to the privacy of the problem, its rarity and attribution to external causes. Male and older subjects show, in general, higher levels of violence legitimization. PMID- 20350456 TI - [Immigrant children in a pediatric department: what social problems?]. AB - BACKGROUND: Hospital Fernando Fonseca is located in a suburban area that houses a great number of immigrants from developing countries. AIMS: To characterize and compare the immigrant and portuguese pediatric populations which have been admitted and referred to Social Service department. MATERIAL AND METHODS: Prospective study, from November 2004 to March 2005; demographic and socioeconomic data, diagnosis and social problems were analysed. RESULTS: A total of 35 children were observed, 22 (62.8%) immigrants, 42.9% of them less than 12 months old, with a predominance of female (54.5%), African origin (81.8%) and poor social-economical status (72.3%). The majority of parents (72.7%) came from a Portuguese Speaking African Country and 58.3% were illegal in our country. Most had a family doctor assigned (81.3%). Nineteen (87.5%) were admitted for organic disease and the social problem was detected later: poverty (9), negligence (7), physical aggression (3), abandon (2), psychological abuse (1), sexual abuse (1). Children were referred to Child Protection Committee (5) and Court (1); 6 children received economical support and 5 needed social support. When compared to the Portuguese population, social problems are more frequent in immigrant children (20% vs.7.5%; p =0,001), especially in African origin (81.8% vs.15.4%; p=0,00); low economic status (7.3% vs.55.6%; p =0.,423 ), poverty (37.5% vs. 26.6%; p=0.313) and physical aggression (13% vs. 8.3%; p =0.313) were more frequent in the immigrant and negligence being the most frequent social problem in the Portuguese population (33.3% vs. 29%; p =0.313). DISCUSSION: The growing number of immigrants and their social deficiencies raises important questions related to health care and social support for these families, to facilitate their social integration. PMID- 20350457 TI - [Ambulatory surgery in urology: first numbers of a successful program]. AB - The ambulatory surgery includes those surgical procedures that require a small period of post-operative recovery so that the patients will be discharged from the hospital in the same day of the surgical intervention. In Urology, the vast amount of pathology that allows the cure with medium and low complexity surgical procedures makes this specialty a privileged one in which ambulatory surgery is concerned. In this paper the authors propose to describe how their Urology group works in the ambulatory field. 472 patients where reviewed in an evaluation period from January 2006 to April 2008. The medical appointment protocol is summarized as well as the most common surgical procedures and complications. Annually we operate an average of 200 ambulatory patients and this represents about 22% of the hole surgical activity of the Urology group. The majority of the surgeries are circumcisions and vasectomies (always associated with other small procedures). There is a 5 hours weakly period where a total of 5 to 6 patients are operated. Surgical complications represented 1.6% of total procedures, all of them late ones. With this specific ambulatory program our service managed to reduce drastically the waiting time for this kind of procedures (now-a-days is about 3-4 weeks), with a satisfaction rate of about 95%. According to the great outcomes, low complications rate and great acceptance of the patients, the development of this unit is without doubt a winning project in patients care. PMID- 20350458 TI - [Tobacco and male infertility: a retrospective study in infertile couples]. AB - INTRODUCTION: Different studies have shown an association between smoking habits and the presence of abnormal spermograms. However these reports have not been consistent throw out the literature. OBJECTIVE: To analyze the effects of cigarette consumption in semen parameters from men attending our infertility outpatient clinic. METHODS: Retrospective comparative study of 327 men (417 spermograms) from an initial population of 372 men attending the infertility outpatient clinic of our institution during the year of 2007. The semen parameters were first compared between smokers and nonsmokers and then a heavy smokers/light smokers analysis took place. RESULTS: From the 327 men included in the study, 135 (41%) were smokers and 55 (40.7%) were heavy smokers. The demographic characteristics were similar between groups. The tobacco use was associated with an increased incidence of oligo/zoosperm, without difference in the other semen parameters. It was also noted a negative correlation between heavy smoking habits and semen volume abnormalities. CONCLUSIONS: The results of the present study suggest that smoking negatively affects male fertility. PMID- 20350459 TI - [Intra and extra-familiar sexual abuse]. AB - The sexual abuse of a child or young person constitutes a major social and public health problem and there is recent evidence that intra-familial (IF) sexual abuses are more serious in their consequences than extra-familial (EF). However, there are no studies on this phenomenon in Portugal. Thus, the aim of the present study is to contribute to a better characterization of these types of abuses and to identify possible differences between IF and EF cases. A retrospective study was preformed based on medico-legal reports related to victims below the age of 18, suspected of being sexually abused (n = 764), corresponding to 67% of the total of observed sexual crimes. Results revealed that 34.9% of the abuses are IF and they show statistically significant differences when compared to EF cases. These are due to the following factors found in IF situations: a) lower victim age; b) closeness between victim and abuser; c) abusers with a higher rate of previous sexual abuse; d) sexual practices of reduced physical intrusion; e) decreased physical violence but increased emotional violence; f) greater delay between last abuse and the forensic exam; g) reduced number of injuries or biological evidence (none in the great majority of the cases). Results point out the existence of several characteristics in IF abuse that have been identified as factors that influence the severity of the abuse consequences. Among them are: a) lower victim age; b) greater proximity to the abuser; c) increased amount of emotional violence. These factors account for the reduced visibility of this kind of cases and therefore explain their delayed disclosure and diagnosis. The association of this fact with the reduced intrusiveness of this sort of practice and the consequent decrease in number of injuries and other evidence leads to a marked reduction of the number of cases where evidence of the abuse can be found by physical examination alone. The above aspects underlie the need of using different strategies to diagnose and support the victims, namely, systematic denouncement by professionals who suspect this type of abuses, and systematic forensic psychological examination for better valorization of the victim's testimony as well as the veracity of its content. PMID- 20350460 TI - [Cross-cultural psychometric assessment of the Bermond-Vorst alexithymia questionnaire]. AB - The alexithymia construct was introduced by Nemiah and Sifneos in the early 70s. It is a multifaceted personality construct that has been recognized associated with various conditions of health disorders. Nonetheless, despite the abundant literature, due to methodological weaknesses, a great share of the studies has been proved of questionable validity and reliability. In recent years a new self report instrument has been developed, the Bermond-Vorst Alexithymia Questionnaire (BVAQ), meant to assess the alexithymia construct in a more comprehensive way than the more commonly used 20-item Toronto Alexithymia Scale (TAS-20). The aim was to investigate the cross-cultural psychometric properties of the Portuguese version of the BVAQ. In this study, carried out in a sample of university students (n = 369), we began testing the originally proposed 5-factor structure, by means of a factor analysis; just to proceed thereafter with the internal consistencies determination. Furthermore we investigated the stability, as well as its convergent validity with the Toronto Alexithymia Scale--20 items (TAS-20). Principal Components Analysis showed that internal structure of the 40 items acceptably fitted into the 5-factor solution. The mean total score differs about 0.6 SD from the original Dutch sample. Internal consistencies are also acceptably about the ones in the original sample: Cronbach's alpha = 0.82 for the global scale and a mean 0.77 for the subscales. Moreover the instrument is reliably stable; and the expected correlations between BVAQ and TAS-20 subscales support evidence of BVAQ's validity. The Portuguese version of the BVAQ is a highly promising new instrument to comprehensively assess alexithymia, and its use can therefore be recommended. PMID- 20350461 TI - [Streptococcal pharyngitis: clinical suspicion versus diagnosis]. AB - INTRODUCTION: Pharyngitis is a very prevalent illness in the ambulatory care setting. Its diagnosis is a challenge, especially in the differentiation between the viric and streptococcal causes. MATERIALS AND METHODS: A formulary was made to register the clinical and laboratory data; a throat swab for culture was obtained from all the children who presented to the emergency department with sore throat and/or signs of pharyngitis/tonsillitis, for a period of three months (15th of April to 15th of July of 2006). The signs and symptoms, prescribed antibiotherapy and frequency of false diagnostics were evaluated and the clinical suspicion compared with the diagnosis by culture. RESULTS: 158 children were evaluated, with a median age of four years, with a male predominance (56%). The period that showed the greatest number of cases was the first fifteen days of May. Forty-three percent of the cultures were positive for Streptococcus pyogenes. The more frequent signs and symptoms in pharyngitis were pharyngeal erythema (98%), fever (86%) and sore throat (78%). A significative statistical difference was found for cough, scarlatiniform rash, tonsillar exudate, palatal petechiae and tonsillar swelling. Of the signs and symptoms studied, only three of them presented a positive predictive value superior to 50%: scarlatiniform rash (85%), palatal petechiae (63%) and cough (57%). The presence of tonsillar exudate had a positive predictive value for non-streptococcal pharyngitis of 70%. Fifty-three percent of the doctors considered streptococcal pharyngitis highly probable, and from this, 56% had a positive culture for Streptococcus. Those who considered a low probability, the culture was positive in 28%. There were 37% of false diagnosis. DISCUSSION: The distinction between streptococcal pharyngitis and non-streptococcal pharyngitis is not always correct when based on clinical characteristics. The use of diagnostic tests is important in order to avoid unnecessary antibiotherapy as well as to allow the correct use in the positive cases. PMID- 20350462 TI - [Co-morbidity and functionality: observational study of a cohort of patients]. AB - Hypertension, Diabetes Mellitus, Cardiac Ischemic Disease and Asthma are chronic diseases that often coexist. Studies on consequences of co-morbidity conclude that the competition of illnesses can be associated with physical and social disability and a higher request of Health services. This study intends to describe the alterations in co-morbidity of a cohort of sick people between 2003 and 2007, to relate it with functionality and to characterise their impact on health resources. The study is observational. A random sample of 110 sick people, stratified by age and gender, was obtained from the database COMORB4DC. Variables were studied on specific domains: demographic, social, morbid-mortality, health resources and functionality. Health problems are classified according to ICPC2. The test of marginal homogeneity, the test of the signals, the test of Mann Whitney and the test of Kruskal-Wallis were used for statistically analysis. The majority of the sample has 65 or more years. The most frequent comorbidities between the four chronic index diseases, in the years of 2003 and 2007, are hypertension with diabetes and the hypertension with ischemic cardiac disease. In the set of the locomotion tasks, physical and instrumental autonomy, only 8% of the sick people are totally independent and 47% are autonomous, these mainly had to use ways of support. Between 2003 and 2007, it is verified a difference (p < 0.001) in the average of identified health problems and in the number of problems grouped in classes. The dependence in locomotion is only associated with a superior number of illnesses (p = 0.033), of used resources of health (p = 0.005) and prescribed drugs (p = 0.001). It is verified to exist a correlation among the number of chronic diseases and the number of contacts with the health centre (r = 0.434, p < 0.001). The collected data on co-morbidity, functionality, resource to social assistance activities and medication allow us to better know the complex network of co-morbidity. This can help us make earlier diagnosis, more accurate prognosis and creating health quality and management plans. The repetition of the study with another interval of time can give us more knowledge on this net of relations. It is essential to effectively provide population with specific health resources and to link primary, secondary and tertiary care. PMID- 20350463 TI - [The premedical syndrome: does it exist in Portugal?]. AB - INTRODUCTION: In Portugal, the medical school selection process relies exclusively on past academic results, involving the most stringent criteria of all courses, with no attention given to the personality traits of the students. In a competitive context, perfectionism dimensions may be relevant to consider. Socially Prescribed Perfectionism (SPP) has been correlated with Neuroticism, while Self-Oriented Perfectionism (SOP) is strongly associated with Conscientiousness. These domains of personality have been linked (lower levels of Neuroticism and higher levels of Conscientiousness) to academic and professional success in Medicine. The premedical syndrome describes premedical students as overachieving, excessively competitive, cynical, dehumanized, overspecialized and narrow. Our main objective was to compare SPP and SOP levels between Medical and Humanities students, as they may be possible indicators of the premedical syndrome among Portuguese medical students. MATERIAL AND METHODS: The Portuguese version of the Multidimensional Perfectionism Scale was administered to 908 undergraduate students from Medicine and Humanities courses of Coimbra University. The sample covered students from the 1st to the 5th year of the courses but most of the students were from the 1st year (n=436). RESULTS: With respect to SPP, significant statistical differences were found, with Medicine students showing lower levels (mean 48.60+/-11.02; p=0.023) than Humanities students (mean 50.00+/-9.56). No significant differences were found in SOP. DISCUSSION AND CONCLUSION: Our results are reassuring, suggesting the lack of a negative impact of the medical school selection process in the personality traits of the students and the probable absence of the premedical syndrome. PMID- 20350464 TI - [Psychopharmacology in medical illness: cardiology, nephrology, hepatology]. AB - The high prevalence of psychiatric disturbances in the context of medical illness and its association with worse prognostic of the last one, are the reasons for which it becomes essential that the doctor, not psychiatrist, has the skills in the use of psychopharmaceuticals. A systematic review of the literature published until January of 2006 was done, through MEDLINE, using as key-words psychiatric illness, renal illness, hepatic illness, cardiovascular illness, psychopharmacology. The reviewed studies include original articles, reviews and observational studies. 39 articles were selected for its adequacy and acquired for the accomplishment of this revision. The authors intend to review the use of the several classes of psychopharmaceuticals, its risks and benefits, according to the different medical illnesses. The first part of this article will have is focus in the area of cardiology, nephrology and hepatology. PMID- 20350465 TI - [Acute liver failure]. AB - Acute liver failure refers to the rapid development of severe acute liver injury with impaired synthetic function in a patient who previously had a normal liver or a well compensated liver disease. Its aetiology is diversified and it provides one of the best indicators of prognosis thus being crucial its quick identification. Because it can progress to multiple organ failure syndrome these patients should be managed in an Intensive Care Unit. The first therapeutic approach consists of intensive care support until treatment for specific aetiologies can be started. Besides encephalopathy, many other complications can develop causing the high rates of morbidity and mortality of acute liver failure and so they need tight surveillance and treatment. Liver support systems are therapeutic options still in study and without proven success in a long term period which makes hepatic transplantation the final therapeutic. Given the wide limitations of hepatic transplantation the final decision is based on a correct diagnosis and prognostic scoring systems. PMID- 20350466 TI - [Sexual activity after spinal cord injury--therapeutic help]. AB - Spinal cord injury affects man in his physical and psychic features, making him go through changes and conditioning his sexual performance. This article presents a brief review of the concept and the epidemiology of spinal cord injury, as well as erectile physiopathology. Since sexual rehabilitation considers the evaluation and the restoration of erectile dysfunction, this article reviews the therapeutic means that allow sexual life recovery, allowing a sexual life with quality, maximizing existing potentialities and promoting adaptation to limitations. PMID- 20350467 TI - [Economic evaluation of capecitabine use as first line treatment in patients with advanced gastric carcinoma in Portugal]. AB - INTRODUCTION: Gastric cancer is a highly prevalent disease in Portugal with impact on morbidity and mortality. The approach to a stomach cancer depends on the disease status and prognosis at the time of diagnosis. Surgical resection is the only potentially curative treatment. Up to now, palliative chemotherapy has been the only advantageous therapy option for patients with unresectable advanced gastric cancer or after recurrence, with a median survival of six to nine months. Among the drugs with a known antitumor activity, 5-fluorouracil (5-FU) and cisplatin have been widely used in advanced gastric cancer, either in monotherapy, or in combination. However, 5-FU is administered by intravenous infusion, which requires the insertion of a central venous catheter or the patient's hospitalization and is therefore inconvenient and uncomfortable. OBJECTIVES: Evaluation of the incremental cost in Portugal of using capecitabine as first line treatment in patients with advanced gastric carcinoma as an alternative to 5-FU, both used in association with cisplatin. METHODS: The study was carried out using the Portuguese National Health Service (NHS) perspective, through an analysis of cost minimization, considering data from a phase III clinical study (ML17032) that demonstrates the non-inferiority of capecitabine versus 5-FU, both in association with cisplatin. A Markov model was developed to evaluate the treatment costs, using a cohort of patients with advanced gastric carcinoma and a timeframe of five cycles. This analysis considered only direct costs. RESULTS: The incremental cost analysis demonstrated savings of 5,868.60 euro per patient with capecitabine therapy (base scenario). The results obtained when considering alternative scenarios (sensitivity analysis), particularly that related to the 5-FU Administration method, reinforce the base scenario savings result. CONCLUSIONS: The analysis conducted demonstrated that the use of capecitabine+cisplatin (CAP-cis) allows a cost reduction when compared to the alternative 5-FU+cisplatin (5-FU-cis). Capecitabine clinical efficacy is not inferior to 5-FU and it has a more convenient and comfortable administration method. It also eliminates the risk of complications associated with intravenous perfusion, consequently reducing the need for hospitalisation. The replacement of 5-FU with capecitabine is shown to be economically advantageous. PMID- 20350468 TI - [Ethical dilemmas in health]. AB - It is difficult to speak of ethic dilemmas in a society that has relativism as the oficial philosophical and political doctrine, i.e., stable values and behavior references, are denied, both in health care and in any other area of human knowledge. In the field of medical sciences it is even pretended to pass from the observational methodology to a field of manipulation and manipulability. It is the very Ethic that is presented as a dilemma. In these conditions one needs to know the lines of thought that are defended, to replace and make disappear the stable ethic references: ecletism, historicism, scientificism, pragmatism, and nihilism itself, that lead to the 'new ethic paradigm', that has created by itself a pseudo-spirituality. The truth is we are adrift in the 'Ethic of Convenience' which changes according to the majorities. In this setting the way to go is to rediscover the abandoned ethic values: only with an objective ethic, with sound references and foundations, it is possible to re-establish and perfect the patient-physician relationship, for a better social health. And this begins with the ethic problem of human life. PMID- 20350469 TI - [Medicine in ancient Mesopotamia--part 1]. AB - The present work summarizes the more elucidating aspects on the foundations and the practice of the medicine in Antique Mesopotamia, since the invention of the writing, more than 5000 thousand years ago, and the beginning of our era. The first part of the article includes a brief perspective about the political and social evolution that characterized those archaic civilizations, as well as the inventions and knowledge further used by the following Humanity's generations. Most of what is known on the subject, as well as the history and political-social events that occurred in the region during that remote epoch, resulted of the laborious decoding of about half a million small clay plates or fragments with text engravings in cuneiform characters that were discovered since the middle of the XIX century in the ruins of the main cities of the Babylonian and Assyrian empires. The second part embraces exclusively the main characteristics of the medicine in Ancient Mesopotamia, in its main facets: concept of disease, healers and practice. The disease was considered a divine punishment or resultant from a malign influence. In that base, the medicine began by being preventive, by the use of appropriate amulets, or by offerings or sacrifices intending to pacify those malign forces. The treatment of the generality of the diseases privileged the expulsion of those spirits and malign influences from the patient body, purifying it, which was done by the specific intervention of an ashipu (clergyman exorcist); not having results, the treatment was continued by the asu (practical healer) that appealed to a group of physical manipulations, limited surgical acts and the administration or application of prescriptions, resultants of the mixture of organic and inorganic substances. In case of failing, the patients (as well as individuals or rein leaders) could fall back upon a priest diviner (baru) who, by examination of the organs of an animal especially sacrificed for the effect, would give a final decision about the disease or the future. Separated this more occult facet, nourished in religious faiths and in the magic, the medicine of Ancient Mesopotamia included rational knowledge, certainly as the result of a systematic patients observation and semiotic interpretation. From those observations and knowledge referred to the Sumerian period, carefully logged, refined and transmitted to the following generations, a valuable collection of texts was built with the description of symptoms, signs, diagnosis and prognostic of the most common diseases, still identifiable in the present. PMID- 20350470 TI - [Sclerosing mesenteritis]. AB - The Sclerosing Mesenteritis is a rare idiopathic disease. It represents the final stadium of progression of the chronic inflammatory illnesses of the intestinal mesentery, with predominance of fibrosis. The clinical manifestations are varied and unspecific. Diagnosis, that demands high degree of suspicion, can be presumed for imaging study, that discloses heterogeneous mass with tumor-like appearance, and confirmed on the basis of anatomo-pathological examination. The treatment is empirical and the prognostic is habitually favourable, over all in initial stadiums of the illness, being in a minority fatal. The authors describe the clinical case of a 50 years-old woman, admitted in the hospital for abdominal pain, ascitis and fever and that by radiological suspicion of peritoneal carcinomatosis and negative complementary study for primitive neoplasm, was submitted to an exploring laparotomy. Observed accented thickening of the mesentery that formed an extensive adherent conglomerate of bowel loops, whose biopsy had disclosed to be a sclerosing mesenteritis. Was verified an irrelevant answer to the treatment and an unfavourable, lethal, clinical course. The authors provide a literature review concerning the most relevant aspects of this disease. PMID- 20350471 TI - [Rickets vitamin-D-dependent type 2]. AB - Rickets is a rare child disease especially in developed countries. Nutritional rickets remains the most prevalent condition, although congenital forms are well known. In the latest group, vitamin D dependent rickets type II is the rarest form and it can course with or without alopecia. There is a mutation on the receptor for vitamin D, with peripheral resistance to the vitamin D action. The authors present two clinical cases of vitamin D dependent rickets type II, in which the alopecia was a peculiar clinical sign that allowed the diagnoses. With prolonged calcium infusions, we achieved normal seric levels of calcium and correct bone disorders; alopecia persisted. This treatment is the most effective way to control the disease. PMID- 20350472 TI - [Large vessel vasculitis in a patient with fever of unknown origin]. AB - Fever of unknown origin (FUO) is a challenging diagnosis. Recently, 18F fluorodeoxyglucose positron-emission tomography (FDG-PET) has emerged as an useful exam to its diagnosis. The authors present a case of a 64-years-old woman with an aortic mechanical valve that was admitted to the internal medicine department because of fever, weakness and weight loss of 2 months duration. Her physical examination was unremarkable. Laboratory findings showed microcytic anemia, no leukocytosis, and elevated C-reactive protein and erythrocyte sedimentation rate. Microbiology, immunology and imaging studies were normal. A FDG-PET was performed, which showed 18F-FDG uptake in aorta and its branches arterial wall. Treatment with corticosteroids was started with good response. This exam, although not sensitive for temporal arteritis when only smaller vessels are involved, permits the diagnosis of large vessel vasculitis with involvement of arteries that can not be biopsied. PMID- 20350473 TI - A systematic review of outcome measures used in forensic mental health research with consensus panel opinion. AB - OBJECTIVE: To describe and assess outcome measures in forensic mental health research, through a structured review and a consensus panel. DATA SOURCES: A search of eight electronic databases, including CINAHL, EMBASE and MEDLINE, was conducted for the period 1990-2006. REVIEW METHODS: In the structured review, search and medical subject heading terms focused upon two factors: the use of a forensic participant sample and the experimental designs likely to be used for outcome measurement. Data extraction included general information about the identity of the reference, specific information regarding the study and information pertaining to the outcome measures used. The consensus exercise was implemented in two stages. At the first stage, participants were asked to complete ratings about the importance of various potential areas of outcome measurement in a written consultation. At the second stage, they were asked to attend a consensus meeting to review and agree results relating to the domains, to consider and rate specific outcome instruments identified as commonly used from the structured review and to discuss strengths, weaknesses and future priorities for outcome measurement in forensic mental health research. RESULTS: The final sample of eligible studies for inclusion in the review consisted of 308 separate studies obtained from 302 references. The consensus group agreed on 11 domains of forensic mental health outcome measurement, all of which were considered important. Nine different outcome measure instruments were used in more than four different studies. The most frequently used outcome measure was used in 15 studies. According to the consensus group, many domains beyond recidivism and mental health were important but under-represented in the review of outcomes. Current instruments that may show future promise in outcome measurement included risk assessment tools. The outcome measure of repeat offending behaviour was by far the most frequently used, occurring in 72% of the studies included in the review. Its measurement varied with position in the criminal justice system, offence specification and method of measurement. The consensus group believed that recidivism is only an indication of the amount of antisocial acts that are committed. CONCLUSIONS: A wide range of domains are relevant to assessing outcomes of interventions in forensic mental health services. Evaluations need to take account of public safety, but also clinical, rehabilitation and humanitarian outcomes. Recidivism is a very high priority; the public expects interventions that will reduce future criminal behaviour. Greater attention needs to be given to validity of measurement, given the enormous variety of approaches to measurement. More research is needed on methods to take account of the heterogeneity of seriousness of forms of recidivism in outcome measurement. Validity of self-report instruments regarding recidivism also needs examination by further research. Mental health is clearly also an important dimension of outcome. The review provides clear support for the view that domains such as quality of life, social function and psychosocial adjustment have not been extensively employed in forensic mental health research, but are relevant and important issues. The role of such instruments needs more consideration. PMID- 20350474 TI - [Treatment of paracetamol poisoning to revision]. PMID- 20350475 TI - [Intravenous or oral N acetylcysteine therapy in paracetamol poisoned patients. Should treatment guidelines be reviewed?]. AB - Danish paracetamol (PCM) poisoned patients are treated with N-acetylcysteine (NAC) intravenously for 36 hours. This probably leads to overtreatment. Today, patients with poor prognoses can be identified and, in addition, NAC may have serious side effects. We reviewed the literature (route of administration, duration and timing of treatment) and found that intravenous NAC often leads to side effects (some serious), primarily when serum paracetamol is low. These patients are often only mildly poisoned and they may therefore benefit from a shorter, orally administered regimen (equally efficient and with fewer side effects than intravenously administered NAC). PMID- 20350476 TI - [Management of hypertension in the hypertension clinic]. AB - INTRODUCTION: A recent Cochrane report concluded that an effective system for hypertension control has yet to be identified. This manuscript presents results from four years' work in a nurse-guided hypertension clinic. The aim of the hypertension clinic was to reduce the number of physician-consultations and to optimize hypertension treatment. MATERIAL AND METHODS: All patients were initially examined by physicians. All follow-up visits were performed by the nurses of the hypertension clinic. They initiated and titrated antihypertensive medication according to a treatment algorithm or the physicians' instructions. Blood pressure (BP) measurement and recording of risk profile were performed in accordance with guidelines from the Danish Hypertension Association. RESULTS: During the four years, 186 patients were treated at the Hypertension Clinic. A total of 130 were discharged to general practice. 95% of these reached their target BP. In all, 56 patients continued treatment at cardiological or nephrological out-patient clinics, or preferred to stop their treatment at the hypertension clinic and refused further referral. Most of the patients received combination therapy with 2-7 different antihypertensive drugs. The three primary antihypertensive drugs were the three first drugs to be used and they comprised the majority of the combination therapy. Many patients received betablockers either as an antihypertensive drug or because of ischemic heart disease. CONCLUSION: Despite many risk factors and severe hypertension, 95% of the patients achieved their target BP. We hope the results will inspire physicians and GP's to adapt the concept. PMID- 20350477 TI - [Percutaneous stented pulmonary valve implantation]. AB - INTRODUCTION: A number of congenital cardiac malformations involve the right ventricular outflow tract and are often treated with a biological valved conduit. The longevity of these valves is limited due to graft degeneration, which causes progressive valvular dysfunction and subsequently right ventricular failure. Due to the young age of these patients, repeat surgery can be expected and this has motivated the invention of the percutaneous stented valve implantation (PPVR). MATERIAL AND METHODS: We retrospectively examined 13 patients (mean age 26 +/- 10 years) treated with PPVR between 2006 and 2008 at our institution. Indications for PPVR were conduit dysfunction with severe stenosis and/or regurgitation, reduced exercise capacity and right ventricular dilatation. RESULTS: In all patients, immediate haemodynamic improvement occurred with full valvular competence after PPVR. The pressure gradient was reduced from 43 (+/- 15) mmHg to 12 (+/- 7) mmHg (p = 0,05) in patients with combined regurgitation and stenosis and 47 (+/- 14) mmHg to 12 (+/- 2) mmHg (p = 0,05) in patients with isolated stenosis. At mean follow-up after 141 (+/- 140) days, no reintervention had been required. CONCLUSION: Significant haemodynamic and clinical improvement occurred after PPVR in all patients and no major complications occurred. PPVR remains a safe and minimally invasive treatment modality, and our study demonstrates that PPVR can be safely performed in a low volume setting. PMID- 20350478 TI - [Laparoscopic versus right-sided hemicolectomy in cancer of colon therapy]. AB - INTRODUCTION: In Denmark, we are still debating whether a laparoscopic approach is beneficial for patients scheduled for right-sided hemicolectomy. The aim of this study was to compare the outcome of laparoscopic versus open resection for right-sided colon cancer. MATERIAL AND METHODS: Using the Danish Colorectal Cancer Group (DCCG) database, we identified two groups each with 42 patients who underwent either laparoscopic right hemicolectomy (LRH) or open right hemicolectomy (ORH). The two groups were compared with respect to demographic data, length of hospital stay, number of glands harvested, blood loss, surgical complications and mortality. RESULTS: The length of hospital stay was significantly shorter in the LRH group than in the ORH group (five vs. six, p = 0.023). Furthermore, the number of lymph nodes harvested was significantly larger in the LRH group than in the ORH group (23 vs. 15, p < 0.001). We found fewer anastomotic leaks (three vs. five), fewer patients with postoperative complications including anastomotic leaks (eight vs. 14) and lower operation related mortality (zero vs. three). None of these differences were statistically significant. CONCLUSION: LRH is comparable to ORH with regards to morbidity, mortality and blood loss. Furthermore, LRH is associated with a shorter hospital stay and a higher radical lymph node harvest than ORH. The results and the thesis that LRH will result in fewer hernias and better cosmetic outcomes makes LRH a promising surgical procedure. PMID- 20350479 TI - [22q11 deletion syndrome]. AB - 22q11 deletion syndrome (formerly named CATCH22, DiGeorge, Velo-Cardio-Facial, Caylor, Kinouchi and Shprintzen syndrome) occurs in approximately 1/2000 to 4000 children. The genetic lesion is remarkably uniform, occurring mainly as 3 or 1.5 MB deletions in the 22q11.2 region. However, the clinical manifestations are variable and manifestation in several organ systems often occur. In this review we describe the various manifestations of the syndrome. Finally, we suggest strategies for diagnosing, evaluating and organizing the treatment for Danish patients with this syndrome. PMID- 20350480 TI - [22q11 deletion syndrome: considerable phenotype variability]. AB - 22q11 deletion syndrome is one of the most frequent syndromes with an estimated prevalence of 1:2000-4000 live births. The syndrome is known to be associated with congenital cardiac malformations, hypocalcaemia and immunodeficiency. We present two cases with rhinopharyngeal insufficiency, cognitive impairment, developmental delay and behavioural problems. These symptoms are even more often associated with the syndrome than the former manifestations. Early diagnosis is important to prevent complications and provide proper support to patient and family. PMID- 20350482 TI - Therapeutic angiogenesis for ischemic disorders: what is missing for clinical benefits? AB - The idea of promoting angiogenesis in ischemic tissues remains an undisputed therapeutic approach for the treatment of myocardium and skeletal muscles that lack sufficient blood supply. However, clinical experiences from several large trials indicated that delivery of proangiogenic factors to patients suffering from myocardial infarction and leg ischemia has not shown significant benefits. Despite continuous success in various animal disease models, why has this simple principle not shown proof of concept in patients? What has been missing in the trial deign? What are the differences between animal models and patients? What are the optimal components for promoting functional collateral networks? This brief review discusses molecular mechanisms underlying arteriogenesis and proposes novel approaches for improvement of therapeutic outcomes. PMID- 20350481 TI - mTOR signaling: a central pathway to pathogenesis in systemic lupus erythematosus? AB - Systemic lupus erythematosus (SLE) is a common autoimmune disease with unclear etiology. Treatments for it often provide inadequate control of disease activity or are limited by side effects. Recent studies have shown that rapamycin can be an effective treatment in both murine lupus models and human SLE. We demonstrated that rapamycin could directly alter molecular abnormalities in SLE T cells related to calcium signaling but not mitochondrial function. However, in light of increased knowledge of the role of mammalian target of rapamycin (mTOR) signaling throughout the immune system, several other potential sites of rapamycin action have been revealed. Specifically, mTOR regulates the production of interferon alpha and the maintenance of immune tolerance at the level of the regulatory T cell and the dendritic cell, and can promote Th2 versus Th1 immune responses. Thus mTOR offers a window into diverse facets of lupus pathogenesis as well as a unifying narrative in our understanding of the therapeutic efficacy of rapamycin in SLE. PMID- 20350483 TI - HIV-1 latency and eradication of long-term viral reservoirs. AB - HIV-1 infection is characterized by a continuous viral replication throughout the illness that can be controlled to some extent by effective treatment. Early during primary infection, latent reservoirs where the virus remains hidden in metabolically inert cells are established. These reservoirs are responsible for a low-rate viral replication that can be observed even during effective treatment and are a major obstacle for the complete eradication of the infection. This low rate viral replication also comes from anatomical sites where drug penetration is limited and only a suboptimal drug concentration can be achieved. Further understanding of the mechanisms underlying HIV-1 latency is of primary importance to develop new strategies that ensure the complete destruction of reservoirs and, therefore, the eradication of the infection. PMID- 20350484 TI - Crossing the boundaries: stem cells and gene therapy. AB - Oncolytic virotherapy is an emerging therapeutic modality for the treatment of cancer. It entails construction of viruses with the ability to selectively target and lyse tumor cells. This branch of therapy has significantly advanced in the past decade, heralded by the development of several novel viruses. Despite the initial success of oncolytic virotherapy in the preclinical setting, however, this treatment modality remains hindered by several obstacles. First, failure to achieve effective viral delivery to targeted tumor beds is a well known limitation. Second, the virus-neutralizing mechanisms of the host immune system, which are in place to protect from viral pathogens, may also hinder the therapeutic potential of virotherapy. One approach to tackling these shortcomings is the use of cell-based carriers to both help with delivery of the virus and shield it from immunosurveillance. Stem cells have recently surfaced as a potential cell-based candidate for delivery of virotherapy. Their unique migratory and immunosuppressive qualities have made them an exciting area of investigation. The focus of this review is to discuss the benefits of stem-cell based delivery of oncolytic virotherapy and its role in cancer treatment. PMID- 20350485 TI - Treatment of ovarian cancer by monoclonal antibodies. AB - Despite the recent advances in its management using cytoreductive surgery and chemotherapy, ovarian cancer remains the most lethal gynecological malignancy. One possible treatment strategy that may improve patient outcome is the use of monoclonal antibodies (mAb) that selectively target tumor cells expressing tumor associated antigens, and thus offer potential benefits such as avoiding the cytotoxic side effects in normal tissue caused by traditional chemotherapeutic agents. Based on the promising results of preclinical studies, various mAb are currently being evaluated in patients with ovarian cancer. Some of them have already demonstrated favorable clinical outcomes in phase I/II studies. However, in contrast to its use for hematological malignancies and certain solid malignancies such as breast and colorectal cancer, mAb-based therapy has not been convincingly proven to be clinically effective in patients with ovarian cancer. As the preclinical results of mAb's therapeutic effects on ovarian cancer have been encouraging, further investigations are needed to establish a more effective, specific, and less toxic treatment strategy for this malignancy. PMID- 20350486 TI - Development of gene therapy for neurological disorders. AB - Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful. PMID- 20350487 TI - Emerging role of microRNAs in prostate cancer: implications for personalized medicine. AB - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. Recent findings indicate that miRNAs are dysregulated in human tumors, suggesting a potential role for these molecules in the pathogenesis of cancer. Thus far, only a limited number of studies have investigated miRNA expression in prostate cancer. Results from these studies indicate that miRNA expression profiles may distinguish carcinoma from non-neoplastic specimens and further classify tumors according to androgen dependence. In addition, a prognostic significance was attributed to specific miRNAs as predictors of clinical recurrence following radical prostatectomy. For a handful of miRNAs, for which a widespread dysregulation in prostate cancer was consistently found, functional investigation has been pursued in prostate cancer experimental models to establish the rationale for the development of miRNA-based therapies. A better understanding of the role exerted by specific miRNAs in the development and progression of prostate cancer is needed, as is a precise definition of their targets relevant to the disease. However, based on available findings, a possible role for miRNAs in the management of prostate cancer as novel biomarkers and new therapeutic targets or intervention tools can be envisioned. PMID- 20350488 TI - Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease. AB - Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi lineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. However, the current understanding from results of clinical trials is that MSC-therapy is safe but its therapeutic efficiency needs to be improved. In this article we will focus on options for genetic manipulation of MSCs and on current progress in adapting genetically-modified MSCs for clinical use in acute cardiovascular disease. PMID- 20350489 TI - The role of peptide libraries in the identification of novel autoantigen targets in autoimmune diseases. AB - Identification of pathogenetically relevant autoantigen targets is a major goal in the study of autoimmune diseases. Indeed it may allow the development of new specific diagnostic tools and facilitate the understanding of the pathogenesis of a disease in order to individualize possible novel treatments. The random peptide library is a molecular biology method that consists of the display of random peptides on live microorganisms. The screening of the library with pooled immunoglobulins obtained from patients affected by an autoimmune disease may lead to the identification of novel autoantigens and of antibodies that are able to bind such antigens with high affinity. Testing patients' sera for the presence of these antibodies may be helpful in the diagnosis of the disease. Moreover such antibodies can be investigated for their functional activity and therefore provide new insights into the pathogenesis of the disease. PMID- 20350490 TI - Cross-talk of alloimmune response and autoimmunity: role in pathogenesis of chronic rejection. AB - Chronic rejection following organ transplantation continues to be a major problem in the long-term survival of the engraftment. Recent literature points to role of both the humoral and cellular alloimmune responses in the pathogenesis of chronic rejection. Our recent studies have provided evidence for alloimmune-response induced de novo development of immune responses to self-antigens in the post transplant period in the pathogenesis of chronic rejection following lung, heart, and kidney transplantation. This review details our current understanding of two distinct yet inter-dependent immune processes in the immunopathogenesis of chronic rejection. PMID- 20350491 TI - The potential of mesenchymal stem cells for neural repair. AB - Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair. PMID- 20350492 TI - Churg-Strauss syndrome: evolving concepts. AB - Churg-Strauss syndrome is a rare, small-sized vessel systemic necrotizing vasculitis that was first described in the early 1950s. Its most typical presentation consists of the appearance, in a patient with late-onset asthma, of vasculitic manifestations, like fever, cutaneous purpura and mononeuritis multiplex. In such a setting, the combination of blood eosinophilia and inflammatory syndrome is highly suggestive of the diagnosis, which can be further supported by the detection of antineutrophil cytoplasmic autoantibodies (ANCN), especially P-ANCA with anti-myeloperoxidase specificity, in almost 40% of the patients, and the presence of eosinophilic granulomas and/or necrotizing vasculitis in an affected-tissue biopsy. Although these disease hallmarks are now well-known, its pathophysiological mechanisms remain to be fully understood. Several gene polymorphisms and immune dysregulations are surely implicated, ranging from direct eosinophil toxicity to T- or even B-cell dysfunctions and, altogether, suggesting the existence of different disease stages and subsets according to the predominantly involved pathway. Only half the patients initially have severe life-threatening manifestations, like cardiac involvement, which require prompt aggressive treatments based on combined corticosteroids and immunosuppressants (mainly cyclophosphamide). Other less severe disease forms can usually be controlled with corticosteroids alone. Even though this current standardized therapy quite effectively and safely obtains remission, more than three-quarters of all the patients will remain corticosteroid-dependent, mostly because of residual asthma and/or eosinophilia. Hence, progress is needed in Churg-Strauss syndrome's therapeutic management, and better understanding of the complex disease mechanisms may aid such a quest. PMID- 20350493 TI - Targeting ion channels for drug discovery. AB - Ion channels are important therapeutic targets which are modulated by a range of currently prescribed drugs. Most of these were developed empirically by traditional pharmacology without knowing their precise target, and the discovery of novel ion channel drugs by high-throughput molecular approaches has proven challenging. A key stumbling-block has been the development of biologically relevant assays with the capacity for randomly screening sizeable compound libraries. While various screening formats exist, e.g., using ion- or voltage sensitive fluorescent dyes, these lack the precision, temporal resolution, and voltage control normally required for monitoring channel modulation. On the other hand, traditional electrophysiology is too slow, technically demanding, and labor intensive for primary screening. Recently, these limitations have been addressed by the development of automated electrophysiology instruments. While retaining much of the fidelity and precision of electrophysiology, these systems also address the main disadvantages by using automation to increase throughput and "de skill" the process. Though the capacities currently attainable are not yet compatible with primary screening, these instruments are nevertheless having a significant impact on drug discovery. By providing high quality, information-rich assays for medium-throughput secondary screening, these instruments bridge significant gaps that, historically, have hampered the early ion channel drug discovery pipeline. PMID- 20350494 TI - Control of HIV-1 replication in elite suppressors. AB - HIV-1 infection usually results in high level of viral replication leading to a progressive decline of CD4+ T cells and eventually to full blown AIDS. Long term non-progressors (LTNPs) are patients who have stable CD4 counts for more than 5 years without antiretroviral therapy. Most of these patients have detectable levels of viremia and eventually will progress to AIDS. Elite controllers or suppressors (ES) represent a distinct subset of untreated patients who appear to be able to completely control viral replication. These patients maintain viral loads below the limit of detection of commercial assays for many years and generally do not show any clinical signs of disease progression. The mechanisms responsible for this remarkable control may lead to the design of effective HIV-1 vaccines. PMID- 20350496 TI - Risk groups and other target groups - preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010-11. AB - Providing guidance on risk and target groups for seasonal influenza immunisation is difficult for the 2010-11 season since there is no experience with the new influenza A(H1N1) virus in its seasonal form. Arguments exist for offering immunisation to people with chronic illness and older people, and also for other risk and target groups including pregnant women. A more rigorous approach is being developed to produce annual evidence-based guidance on risk and target groups for influenza vaccination. PMID- 20350497 TI - Q fever outbreak in Cheltenham, United Kingdom, in 2007 and the use of dispersion modelling to investigate the possibility of airborne spread. AB - We describe the investigation of an outbreak of Q fever in the town of Cheltenham, England. The outbreak was detected in June 2007, and prospective and retrospective case finding identified 30 confirmed or probable human cases. The investigation identified windborne spread of Coxiella burnetii from nearby sheep farms as the most likely source of infection. A telephone survey was conducted to identify risk practices at local farms. Subsequently the atmospheric dispersion model NAME was used to identify whether air from the identified farms with high risk practices had been carried into Cheltenham town centre during the risk period. Three high risk farms were identified and the modelling showed that air from all of these farms was carried over Cheltenham in the estimated risk period. The investigation resulted in an information campaign to farmers and production of improved advice for livestock farmers on reducing the risks of transmitting Q fever to humans. PMID- 20350498 TI - Substantial increase in listeriosis, Denmark 2009. AB - In 2009, 97 cases of listeriosis were reported in Denmark (1.8 per 100,000), a significant rise over the previous year. The increase was seen both in cases of bacteraemia and meningitis and affected mainly people aged 70 years and older. A foodborne outbreak of eight cases was identified by pulsed-field gel electrophoresis typing. No explanation has so far been found for the marked increase in incidence. An increasing trend has been observed since 2003 and possible explanations are discussed. PMID- 20350499 TI - Norovirus outbreaks linked to oyster consumption in the United Kingdom, Norway, France, Sweden and Denmark, 2010. AB - This paper reports on several simultaneous outbreaks of norovirus infection linked to the consumption of raw oysters. Since January 2010, 334 cases in 65 clusters were reported from five European countries: the United Kingdom, Norway, France, Sweden and Denmark. The article describes the available epidemiological and microbiological evidence of these outbreaks. PMID- 20350500 TI - Q fever in the Netherlands: an update on the epidemiology and control measures. AB - Since the steady rise in human cases which started in 2007, Q fever has become a major public health problem in the Netherlands with 2,357 human cases notified in the year 2009. Ongoing research confirms that abortion waves on dairy goat farms are the primary source of infection for humans, primarily affecting people living close (under 5 km) to such a dairy goat farm. To reverse the trend of the last three years, drastic measures have been implemented, including the large-scale culling of pregnant goats on infected farms. PMID- 20350501 TI - Query fever: an opportunity to understand the disease better. PMID- 20350502 TI - Efficacy of linear block at the left atrial roof in atrial fibrillation. AB - BACKGROUND: After extensive encircling of ipsilateral pulmonary vein isolation (EEPVI) for atrial fibrillation (AF), we sometimes observe AF recurrence, or the occurrence of atrial tachycardia originating from the left atrium. This study examined the efficacy of additional linear ablation at the left atrial (LA) roof in combination with EEPVI to prevent arrhythmia recurrences. METHODS: This study included 104 patients with drug-refractory AF (75 with paroxysmal, 29 with persistent). The patients in Group A (n=70) underwent EEPVI treatment alone, and the patients in Group B (n=34) underwent linear ablation at the LA roof in addition to EEPVI treatment. At 1, 3, 6, and 12 months after ablation, patients underwent clinical review and 24-h ambulatory electrocardiogram monitoring to identify asymptomatic arrhythmias. Follow-up included daily trans-telephonic event monitoring, transmitted irrespective of the patient's symptoms. RESULTS: At 12 months, 57% of Group A and 79% of Group B were free of arrhythmias (p<0.05). Cox regression analysis demonstrated that among the variables of age, sex, duration of AF, types of AF (paroxysmal or persistent), LA size, ejection fraction, existence of hypertension, ischemic heart disease, valvular heart disease, history of stroke, and the ablation technique, only the ablation technique of the linear block at the LA roof was the independent predictor of arrhythmia-free recovery after ablation. CONCLUSIONS: EEPVI in combination with the linear ablation at the LA roof is associated with an improved clinical outcome compared with EEPVI alone. PMID- 20350503 TI - Clinical characteristics in patients showing ischemic electrocardiographic changes during adenosine triphosphate loading single-photon emission computed tomography. AB - OBJECTIVES: Although ischemic electrocardiographic (ECG) changes during dipyridamole or adenosine infusion have been reported as a marker for severe coronary artery disease (CAD), few studies have focused on ST-segment changes with adenosine triphosphate (ATP)-loading myocardial single-photon emission computed tomography (SPECT). METHODS AND SUBJECTS: Between January 2003 and August 2008, 4650 consecutive patients underwent ATP-loading SPECT. After 1412 patients with left bundle branch block, pacemaker rhythm, or previous coronary revascularization were excluded, 16 out of 3238 patients (0.5%) showed ischemic ST-segment depression during ATP-loading myocardial SPECT. They were aged 67+/-11 years; 10 were men and 6 women. Of these patients, 8 demonstrated perfusion abnormalities, whereas the remaining 8 showed normal myocardial perfusion imaging. In 6 of the 8 patients with abnormal SPECT, coronary angiography was performed, revealing left main trunk disease in 1 patient, 3-vessel disease in 4, 1-vessel disease with proximal left ascending artery occlusion in 1, and an insignificant lesion in 1. By contrast, no major cardiac event was observed in the 8 patients with normal SPECT during follow-up for an average of 2 years. CONCLUSION: The prevalence of ischemic ST-segment changes during ATP loading is very rare. However, this finding should be taken into account since almost half of the patients, particularly those with perfusion abnormalities, may have severe CAD which requires coronary revascularization. PMID- 20350504 TI - The impact of chronic kidney disease as a predictor of major cardiac events in patients with no evidence of coronary artery disease. AB - BACKGROUND: Normal stress myocardial perfusion images (MPI) generally show good prognosis for cardiovascular events. However, chronic kidney disease (CKD) is one of the important risk factors for coronary artery disease (CAD), and the interpretation of normal stress MPI has not been well established in CKD patients with no evidence of CAD. The purpose of this study was to evaluate the long-term prognostic value of stress MPI in CKD patients with no evidence of myocardial ischemia or infarction. METHODS: Patients who had no history but were suspected of CAD and had normal stress MPI (n=307, male=208, age=67 years, CKD/non CKD=46/261) were followed-up for 4.5 years. CKD was defined as a glomerular filtration ratio of <60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiac death, non-fatal myocardial infarction, and unstable angina requiring hospitalization were defined as major cardiac events. RESULTS: Major cardiac events were observed in 3 of 261 (1.1%) non-CKD patients and 6 of 46 (13%) CKD patients (p<0.001, with log-rank test). CKD was an independent risk factor for major cardiac events (hazard ratio=13.1, p<0.001, multivariate Cox regression analysis). CONCLUSIONS: Normal stress MPI does not always promise a good prognosis for major cardiac events. Even in patients with no evidence of CAD from stress MPI, CKD can be an independent and significant risk factor for major cardiac events. PMID- 20350505 TI - Difference in risk factors between acute coronary syndrome and stable angina pectoris in the Japanese: smoking as a crucial risk factor of acute coronary syndrome. AB - BACKGROUND AND PURPOSE: Metabolic syndrome and chronic kidney disease (CKD) have received attention as new risk factors for cardiovascular disease. This study evaluated differences in key risk factors between acute coronary syndrome (ACS) and stable angina pectoris (SAP) by using traditional coronary risk factors, metabolic syndrome, and CKD. METHODS: Among 1890 consecutive patients admitted to our institution, we studied 140 patients with initially diagnosed ACS and 163 patients with initially diagnosed SAP and compared risk factors between the two groups. Next, the relationship between smoking status after the initial diagnosis of coronary artery disease (CAD) and the incidence of subsequent cardiac event was examined after discharge in 284 patients. RESULTS: Adjusted multivariate analysis showed that only current smoking was an independent predictor of ACS (odds ratio, 2.20; 95% CI, 1.28-3.78; p=0.004) among all risk factors we examined. Treatment with a calcium-channel blocker had a preventive effect on ACS (odds ratio, 0.44; 95% CI, 0.26-0.75; p=0.003), but treatment with a beta-blocker did not. Patients who continued to smoke after CAD was diagnosed had a risk of cardiac events about 5 times that of smokers who quit (adjusted hazard ratio, 5.05; 95% CI, 1.33-19.20; p=0.02). CONCLUSIONS: The risk factors were significantly different between initially diagnosed ACS and SAP. Smoking was a more important risk factor of initially diagnosed ACS. Smoking cessation might have a preventive effect on subsequent cardiac events. Also, we found that treatment with a calcium-channel blocker would help prevent ACS in Japanese patients. PMID- 20350506 TI - Coronary abnormal response has increased in Japanese patients: analysis of 17 years' spasm provocation tests in 2093 cases. AB - BACKGROUND: Abnormal coronary response on acetylcholine test is observed in patients with early coronary atherosclerosis. OBJECTIVES: We analyzed retrospectively the abnormal response rate during 17 years of spasm provocation tests in 2093 consecutive patients. METHODS: We performed 2093 spasm provocation tests, consisting of 1198 acetylcholine tests and 895 ergonovine tests, between January 1991 and December 2007. Spasm provocation test was mainly performed in patients with ischemic heart disease. Abnormal response was defined as transient >90% luminal narrowing during spasm provocation tests. We classified these 17 years into two periods: former period from January 1991 to December 2000, and the latter period from January 2001 to December 2007. In the former period, 1300 spasm provocation tests were performed and 793 spasm provocation tests were done in the latter period. RESULTS: The incidences of hypertension, dyslipidemia, and diabetes mellitus were significantly increased in the latter period. The values of total cholesterol, triglycerides, and fasting blood sugar were also significantly increased in the latter period. The frequency of abnormal response in the latter period was significantly higher than that in the former period (46.0% vs. 33.2%, p<0.05). The frequency of abnormal coronary response to acetylcholine in the latter period was significantly higher than that in the former period (60.0% vs. 34.0%, p<0.01), whereas there was no difference concerning abnormal response of ergonovine between the two periods (31.9% vs. 30.7%, ns). CONCLUSIONS: In Japanese patients, abnormal coronary response to acetylcholine has increased and coronary endothelial dysfunction is suggested to have progressed. PMID- 20350507 TI - A flow-limiting stenosis is the major determinant of exercise-induced myocardial stunning in patients with coronary artery disease. AB - BACKGROUND: Although stress-induced myocardial stunning often develops after exercise testing, determinants of this phenomenon have not been evaluated. METHODS AND RESULTS: Thirty-one patients with 1-vessel coronary artery disease, limited to the left anterior descending artery (LAD), were evaluated by quantitative coronary angiography (QCA) and intracoronary pressure measurements to calculate fractional flow reserve (FFR). In addition, electrocardiogram-gated technetium-99m sestamibi myocardial imaging was acquired >30 min after exercise and 4 h later to assess the development of stunning. Exercise-induced myocardial stunning was observed in 11 patients (35%). In patients with myocardial stunning, a summed stress score (17.3+/-7.1 vs. 8.1+/-6.2, p<0.001), summed difference score (10.3+/-4.1 vs. 2.7+/-1.9, p<0.0001), and wall motion difference score (4.8+/-2.8 vs. 0.9+/-1.1, p<0.0001) were greater than in those without, while diameter stenosis calculated by QCA (55.1+/-17.3% vs. 29.8+/-17.3%, p<0.0001) was greater and FFR reduced significantly (0.54+/-0.13 vs. 0.83+/-0.06, p<0.0001). Of note, 4 out of 21 patients (19%) with <50% LAD stenosis developed myocardial stunning, whereas only one patient with FFR of 0.64 or greater showed stunning. The best cut-off value was determined as 0.64 for FFR and 46% for QCA, providing 91% sensitivity and 100% specificity for FFR (chi-square=57.2), but 91% sensitivity and 80% specificity for diameter stenoses measured by QCA (chi square=17.8). CONCLUSIONS: The major determinant for exercise-induced myocardial stunning was a severe flow-limiting coronary stenosis, which was more important than anatomical evaluation based on luminal narrowing alone. PMID- 20350508 TI - Longitudinal Doppler strain measurement for assessment of damaged and/or hibernating myocardium by dobutamine stress echocardiography in patients with old myocardial infarction. AB - BACKGROUND: The ratio of systolic lengthening to combined late and postsystolic shortening (L/TS ratio) on longitudinal Doppler strain imaging (Doppler SI) may be an index of myocardial viability. We hypothesized that measuring the postsystolic index (PSI) and the L/TS ratio during dobutamine stress echocardiography (DSE) could quantitatively identify viable myocardium with the potential for regional functional recovery. METHODS: Thirty-eight patients with old myocardial infarction (OMI) underwent DSE with Doppler SI and coronary angiography (Group 1). To clarify the value of measuring the PSI and L/TS ratio by DSE with Doppler SI in patients with OMI, these Doppler parameters and visual analysis of wall motion abnormality (WMA) were compared on a segmental basis. To investigate the prediction of regional functional recovery, 10 patients with OMI (Group 2) and stenosis of the infarct-related coronary artery underwent DSE with Doppler SI before and after percutaneous coronary intervention. RESULTS: In Group 1, 143 out of 556 segments showed a biphasic WMA pattern during DSE. There were no segments with evidence of necrosis. The PSI at peak stress was > or =0.25 in 114 out of 143 segments and the L/TS ratio at peak stress was >0 in 82 out of 114 segments. Regarding functional recovery, 42 of the 73 segments with WMA at rest showed improvement after reperfusion. The wall motion score (WMS) showed 86% sensitivity and 71% specificity for predicting regional recovery, while PSI and L/TS ratio showed 61% vs. 84% sensitivity and 60% vs. 79% specificity, respectively. The AUC for the ROC curve of the L/TS ratio as a predictor of regional recovery was significantly larger compared with that of WMS (0.894 vs. 0.783, p<0.05). CONCLUSIONS: The peak stress L/TS ratio could be a specific and quantitative marker for identifying myocardial viability that has the potential for regional functional recovery. PMID- 20350509 TI - The impact of intermittent pneumatic compression devices on deep venous flow velocity in patients with congestive heart failure. AB - BACKGROUND: Intermittent pneumatic compression (IPC) has been used to prevent deep venous thrombosis (DVT), but the effects of IPC on the hemodynamics of popliteal and soleal veins, especially in patients with congestive heart failure (CHF) have not been evaluated. The aim of this study was to evaluate the effects of IPC on the flow velocity of deep veins in the lower extremities and to compare the efficacy of two different types of IPC in deep venous flow enhancement in patients with CHF. METHODS: Flow velocities of popliteal and soleal veins were recorded in 19 patients with CHF and in 19 control subjects using a high resolution linear probe. Peak and mean flow velocities were measured (1) at rest, (2) with sequential foot and calf IPC (SFC-IPC) which consists of an electrically driven air compressor and four air chambers, and (3) with impulse foot IPC (IF IPC) which consists of a pneumatic impulse generator operated at an applied pressure of 130 mmHg. RESULTS: In the resting condition, popliteal venous flow velocity in the CHF group was attenuated (12.8+/-4.7 cm/s vs. 21.1+/-13.5 cm/s; p<0.05). Both SFC-IPC and IF-IPC increased venous velocity, but the increase with IF-IPC in CHF patients was lower than that in control subjects. In the soleal veins, after applying SFC-IPC, the peak and mean velocity in CHF increased to the same extent as in the control group. IF-IPC increased soleal venous velocity in control subjects, but there was no increase in CHF patients. CONCLUSION: Two dimensional Doppler scanning revealed a significant increase in the mean and peak velocities in the soleal and popliteal veins with SFC-IPC but not with IF-IPC in patients with CHF. These results indicate that SFC-IPC could have favorable effects in preventing DVT in patients with CHF. PMID- 20350510 TI - Impact of anticoagulant therapy with dual antiplatelet therapy on prognosis after treatment with drug-eluting coronary stents. AB - BACKGROUND: Although combination therapy for various cardiac conditions with dual antiplatelet therapy (aspirin and thienopyridine derivatives) and warfarin sodium has become increasingly popular, the safety and effectiveness of this aggressive treatment regimen remain unknown. METHODS AND RESULTS: We retrospectively enrolled and analyzed 575 consecutive patients who had been implanted with drug eluting coronary stents. The primary and secondary endpoints were major bleeding complications and major adverse cardiovascular events (MACE), respectively. At the time of discharge, 525 patients (91.3%) were prescribed with dual antiplatelet therapy, and 50 (8.7%) of them received dual antiplatelet plus anticoagulant therapy (triple therapy). The patients treated with triple therapy had a greater prevalence of comorbid conditions, including left ventricular systolic dysfunction and multi-vessel coronary disease compared to those on the dual antiplatelet regimen. During a median follow-up of 459 days, 14 (2.7%) patients receiving dual, and 9 (18.0%) receiving triple therapy reached the primary endpoint (p<0.001). These results show that warfarin use was associated with an increased risk of subsequent major bleeding. On the other hand, the incidence of MACE did not differ between the two groups (p=0.108 by the log-rank test). Multivariate analysis showed that renal impairment was an independent predictor of the risk of subsequent major bleeding in the triple therapy group. CONCLUSIONS: Triple therapy increased the hemorrhagic complications in patients after percutaneous coronary intervention with drug-eluting stents, especially in patients with impaired renal function. Great caution should be taken with patients who necessitate the addition of anticoagulation therapy with warfarin to dual antiplatelet therapy. PMID- 20350511 TI - Predictor of subsequent target lesion revascularization in patients with drug eluting stent restenosis undergoing percutaneous coronary intervention. AB - BACKGROUND: The best way to treat in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The aim of this study was to evaluate angiographic restenosis and target lesion revascularization (TLR) at 8 months after intervention in patients with DES-ISR, and to identify predictive factors of subsequent TLR after treatment of DES-ISR. METHODS AND RESULTS: A total of 100 patients with 105 lesions underwent subsequent intervention for DES-ISR between April 2004 and January 2009. At baseline, focal and diffuse ISR were observed in 76.2% and 23.8%. DES-ISR was treated by five modalities: sirolimus-eluting stent (n=42); paclitaxel-eluting stent (n=24); balloon angioplasty (n=23); cutting balloon angioplasty (n=14); and bare-metal stent (n=2). Angiographic follow-up data were available for 95 lesions (91%). The rates of angiographic restenosis and TLR were 37.9% and 33.3%. Late loss of sirolimus-eluting stent, paclitaxel eluting stent, cutting balloon, and balloon angioplasty were 0.50 mm, 0.49 mm, 0.93 mm, and 1.10 mm. By multivariate analysis, totally occluded ISR (OR 15.43, p=0.0005), diabetes mellitus (OR 3.45, p=0.02), and re-stenting with DES (OR 0.14, p=0.0002) were identified as independent predictors of TLR. CONCLUSIONS: The restenosis rate was significant in this cohort of patients with DES-ISR. Angiographic pattern of DES-ISR and diabetes mellitus are the most important predictors of TLR, whereas re-stenting with DES is protective. PMID- 20350512 TI - Mid-term mortality of very elderly patients with acute myocardial infarction with or without coronary intervention. AB - BACKGROUND: The risk benefit of percutaneous coronary intervention (PCI) in very elderly patients with acute myocardial infarction (AMI) is currently unclear. Here, we aim to identify the characteristics of these patients and clarify their mid-term mortality rate with or without PCI. METHODS AND RESULTS: 77 patients (> or =80 years) were chosen from 506 patients with AMI, and treated with (n=32) or without (n=45) PCI. The mean age and time from onset to admission increased in patients having undergone no PCI. The reasons for PCI refusal were patient/family preference (40%), renal dysfunction (17.8%), or cognitive impairment (13.3%). Patients treated with PCI had lower mid-term mortality than those without PCI (34.4% vs 62.2%; p=0.02), while patients taking beta-blockers displayed a significantly lower mortality rate than those without (18.2% vs 63.6%; p=0.0003). Cognitively impaired patients had a higher mortality rate compared with cognitively normal patients (80.0% vs 46.3%; p=0.005). Multivariate analysis indicated that systolic blood pressure on admission, PCI, and beta-blocker therapy independently decreased mid-term mortality in these patients. CONCLUSIONS: PCI and beta-blocker therapy displayed significantly beneficial effects on mid-term mortality in very elderly AMI patients. Elderly-specific trials concerning coexisting disorders are needed to further examine the treatment-related benefits. PMID- 20350513 TI - Cardiac mortality of premature ventricular complexes in healthy people in Japan. AB - BACKGROUND AND PURPOSE: Premature ventricular complexes (PVCs) are frequently encountered in healthy people. But the association between PVCs and cardiac events is not well established in Japan. We investigated the association of PVCs and cardiac deaths in people without cardiovascular disease in the Jichi Medical School (JMS) Cohort study. METHODS AND SUBJECTS: We conducted a prospective cohort study in 12 districts in Japan as part of the JMS cohort study. Baseline data were obtained between April 1992 and July 1995. We excluded subjects who had myocardial infarction and stroke and those who had not received 12-lead electrocardiograms. Cox's proportional hazard model was used to calculate the hazard ratios (HRs) of cardiovascular mortality of subjects with PVCs, using subjects without PVCs as reference. RESULTS: A total of 11,158 participants (4333 males and 6825 females) were analyzed. Participants were followed for an average of 11.9 years. PVCs were present in 1.4% of men and 1.1% of women. There were 92 cardiac deaths (47 males and 45 females) during the follow-up period. In crude cardiovascular mortality, HRs (95% confidence interval [CI]) were 5.29 (1.64 17.0) in males and 2.14 (0.29-15.5) in females. Age-adjusted HRs were 3.73 (1.16 12.0) and 0.98 (0.13-7.21), respectively. After further adjustment for body mass index, systolic blood pressure, total cholesterol level, high-density lipoprotein cholesterol, and blood glucose, HRs were 3.98 (1.21-13.0) and 0.95 (0.13-7.11), respectively. CONCLUSIONS: We conclude that PVCs are a predictive factor for cardiac death in men without structural heart disease. PMID- 20350514 TI - What variables were associated with the inducibility of ventricular fibrillation during electrophysiologic stimulation test in patients without apparent organic heart disease? AB - OBJECTIVE: The purpose of our study was to determine what variables were associated with ventricular fibrillation (VF) induced during electrophysiological stimulation test in patients without apparent organic heart disease. METHODS: Our study evaluated 77 patients (51+/-15 years) who underwent electrophysiological stimulation test, signal averaging, and Na+ channel-blocker challenge test (pilsicainide test). The subjects were divided into two groups, the Brugada group and non-Brugada group. Further, the patients were divided into three subgroups on the base of symptoms (8, 7 symptomatic; 9, 13 syncope; 28, 12 asymptomatic group; in the Brugada and non-Brugada groups, respectively). Multivariate analyses evaluated the association between baseline clinical factors and the induction of VF. RESULTS: The inducibility of VF was significantly (p<0.0001) higher in the Brugada group (n=33, 73%) than the non-Brugada group (n=4, 13%). The multivariate analysis demonstrated that symptoms (odds ratio (OR) 31.6; 95% confidence interval (CI): 2.3-430.6; p<0.01), type 1 electrocardiogram after pilsicainide test (OR 21.3; CI: 1.7-272.2; p<0.02), and syncope (OR 13.5; CI: 1.2-158.8; p<0.05) were strongly associated with the inducibility of VF, but not with family history, type 1 electrocardiogram in control, positive in late potential, maxDeltaST elevation (>==200microV) after pilsicainide test. CONCLUSIONS: The symptoms, syncope, and type 1 electrocardiogram after pilsicainide test were independently associated with the electrophysiological substrate of VF in patients without apparent heart disease. PMID- 20350515 TI - Influence of the severity of obstructive sleep apnea on heart rate. AB - BACKGROUND: We sought to clarify the influence of the severity of obstructive sleep apnea (OSA) on heart rate (HR) in patients with OSA. METHODS: We examined 136 patients who underwent overnight polysomnography together with 24-h Holter electrocardiography and who were diagnosed as having OSA [apnea-hypopnea index (AHI) >/=5]. The patients were divided into the following 3 groups: 30 with 5/=30 (group C). Mean HRs during 24h, wakefulness, and sleep were calculated. RESULTS: Mean HRs during 24h, wakefulness, and sleep were significantly higher in group C than in groups A and B. Mean HRs during 24h, wakefulness, and sleep correlated positively with AHI (Spearman's rho=0.36, p<0.001; Spearman's rho=0.32, p<0.001; Spearman's rho=0.38, p<0.001; respectively). Multiple regression analyses revealed that lnAHI was independently associated with mean HRs during 24h, wakefulness, and sleep. In 21 OSA patients who started nasal continuous positive airway pressure (nCPAP) therapy, mean HRs during 24h, wakefulness, and sleep were significantly reduced at 6 months after the initiation of nCPAP. CONCLUSION: The severity of OSA was independently associated with mean HRs during 24h, wakefulness, and sleep, and 6-month treatment with nCPAP reduced the values. The prognostic significance of elevated mean HRs during 24h, wakefulness, and sleep is necessary to be clarified in patients with OSA. PMID- 20350516 TI - N-terminal pro-BNP is a novel biomarker for integrated cardio-renal burden and early risk stratification in patients admitted for cardiac emergency. AB - BACKGROUND: The expanding role of cardiac markers - cytosolic [heart-type fatty acid-binding protein (H-FABP) and creatine kinase MB (CK-MB)], myofibril [troponin T (TnT)], and cardio-endocrine [N-terminal pro-B-type natriuretic peptide (NT-proBNP)] - has been clarified in patients with acute coronary syndrome and those with heart failure. However, these applications for early risk stratification in the cardiac emergency, and the influence of renal function on these evaluations have not been fully investigated. PATIENTS AND METHODS: We investigated the prognostic value of these representative cardiac markers and influence of renal function on these evaluations in 165 consecutive patients who were admitted for cardiac emergency because of chest pain or dyspnea. RESULTS: There were significant correlations between TnT and CK-MB (r=0.512, p<0.001), and between H-FABP and TnT (r=0.409, p<0.001) and CK-MB (r=0.254, p<0.01); however, NT-proBNP levels did not show significant correlations with other cardiac markers. There were significant correlations between estimated glomerular filtration rate and NT-proBNP (r=-0.466, p<0.001) and H-FABP (r=-0.235, p<0.001) levels, and between left ventricular ejection fraction (LVEF) and NT-proBNP (r= 0.407, p<0.001) and H-FABP (r=-0.253, p<0.01) levels. Kaplan-Meier analysis showed that median of NT-proBNP, H-FABP, and CK-MB significantly discriminated in hospital cardiovascular death, and multivariate analysis revealed NT-proBNP and LVEF as independent prognostic predictors. CONCLUSION: NT-proBNP is a novel biomarker for integrated cardio-renal burden, and extremely useful for early risk stratification in the situation of cardiac emergency. PMID- 20350517 TI - Differences in left ventricular dyssynchrony between high septal pacing and apical pacing in patients with normal left ventricular systolic function. AB - BACKGROUND AND PURPOSE: Permanent right ventricular apical pacing can result in heart failure due to ventricular mechanical dyssynchrony. The purpose of the study was to define differences in left ventricular dyssynchrony between high septal pacing and apical pacing using tissue Doppler imaging (TDI) and two dimensional (2D) speckle-tracking echocardiography (STE). METHODS: The subjects were 60 patients with normal left ventricular systolic function who underwent implantation of a permanent pacemaker. Patients were divided into two groups with high septal pacing (n=36) and conventional right apical pacing (n=24). Left ventricular dyssynchrony was measured using TDI and 2D-STE. The time difference (TD) between the earliest and latest activated segments obtained from each systolic velocity curve by TDI was defined as TD-TDI. The time differences obtained from systolic strain curves obtained by 2D-STE were defined as TD-RS for radial strain, TD-CS for circumferential strain, and TD-LS for longitudinal strain. RESULTS: The high septal pacing group had significantly shorter TD-TDI (20.0+/-24.3ms vs. 59.7+/-43.0ms, p<0.0001), TD-RS (13.5+/-19.9ms vs. 45.8+/ 24.6ms, p<0.0001), and TD-LS (42.7+/-22.0ms vs. 66.6+/-26.8ms, p=0.001) values compared to the apical pacing group. There was no significant difference in TD-CS between the two groups. CONCLUSION: Left ventricular dyssynchrony was smaller in patients with high septal pacing. The results show that 2D-STE is useful for detection of differences in left ventricular mechanical dyssynchrony in patients with permanent pacemaker implantation, in addition to TDI. PMID- 20350518 TI - Oral sildenafil: potential role in heart transplantation. Review of the literature and personal experience. AB - Early right ventricular dysfunction after heart transplantation (HTx) is a major complication especially in patients with pre-transplant pulmonary arterial hypertension (PH). The possibility to reverse secondary PH using sodium nitroprusside (NPS) or inhaled nitric oxide has been already established and there is a well-known stratification of the incidence of early death after HTx related to the reversibility of PH. Despite this, in a group of patients with irreversible disorders of the pulmonary vascular bed, conventional therapy may not be useful. However, the decision to disqualify non-responsive HTx candidates may be inappropriate, considering that PH unresponsiveness to NPS does not exclude the possibility to decrease pulmonary pressures with other medications. In case of non-responsive patients, the debate regarding the role of new selective pulmonary vasodilators is still open and oral sildenafil use in cardiac transplant candidates and recipients is growing. Despite this, there are many reports of the use of phosphodiesterase 5 inhibitors in patients with chronic heart failure and several studies describe the positive effects of sildenafil in reducing pulmonary vascular resistance and pulmonary arterial pressure and in increasing cardiac output. Oral sildenafil use in cardiac transplant candidates or recipients is still limited. PMID- 20350519 TI - Effects of statin and lipoprotein metabolism in heart failure. AB - Statins decrease serum levels of low-density lipoprotein (LDL) cholesterol and have pleiotropic effects. Statin therapy may have beneficial effects on the clinical outcome in patients with heart failure (HF). HF is associated with lipoprotein components. A recent study suggested that lower levels of high density lipoprotein (HDL) cholesterol were the strongest predictor of worsening HF. In addition, serum total cholesterol (TC) is a prognostic factor for patients with HF. Although the levels of HDL cholesterol, apolipoprotein (Apo) A-I, triglyceride, TC, and LDL cholesterol may be associated with the onset of HF and/or an adverse prognosis in patients with HF, it is not yet clear which lipoprotein plays the most important role in this context. Among these lipoproteins, HDL protects against cardiovascular events by mediating the enhancement of reverse cholesterol transport. Moreover, HDL also has pleiotropic effects, such as anti-oxidant, anti-inflammatory, and anti-thrombotic properties. An increase in HDL cholesterol or ApoA-I, the principal Apo of HDL, may be a therapeutic target in HF. Therefore, we discuss here the usefulness of statins and lipoprotein metabolism for preventing HF. PMID- 20350520 TI - Differences in intravascular ultrasound findings in culprit lesions in infarct related arteries between ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction. AB - BACKGROUND: Previous studies have reported diffuse destabilization of atherosclerotic plaques in acute myocardial infarction (AMI). We used intravascular ultrasound (IVUS) to assess coronary culprit lesions in ST segment elevation MI (STEMI) vs. in non-ST segment elevation MI (NSTEMI). METHODS: Patient population comprised 125 STEMI and 185 NSTEMI patients. IVUS findings included ruptured plaque (a cavity that communicated with the lumen with an overlying residual fibrous cap fragment), lipid-pool like image (a pooling of hypoechoic or echolucent material covered with a hyperechoic layer), thrombus (discrete intraluminal filling defects), and plaque prolapse (tissue extrusion through the stent strut at post-stenting). RESULTS: Culprit lesions had larger external elastic membrane area (13.5+/-4.9mm(2) vs. 11.9+/-4.3mm(2), p=0.002), larger plaque plus media area (10.8+/-4.4mm(2) vs. 9.1+/-4.1mm(2), p=0.001), and greater plaque burden (78.7+/-10.1% vs. 74.8+/-12.0%, p=0.002), and smaller culprit lesion site calcium arc (96+/-90 degrees vs. 153+/-114 degrees , p=0.002) in patients with STEMI than in those with NSTEMI. Culprit lesion plaque ruptures, lipid-pool like images, and thrombus were observed more frequently in patients with STEMI than in those with NSTEMI (46% vs. 29%, p=0.002; 39% vs. 25%, p=0.010; and 34% vs. 21%, p=0.006, respectively). Culprit lesions were more predominantly hypoechoic in patients with STEMI than in those with NSTEMI (62% vs. 40%, p<0.001). There was a trend that post-stenting plaque prolapse was observed more frequently in patients with STEMI than in those with NSTEMI (33% vs. 24%, p=0.081). CONCLUSIONS: Culprit lesions in STEMI have more markers of plaque instability (more plaque rupture and thrombus, and larger plaque mass) compared with lesions in NSTEMI. PMID- 20350521 TI - A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy. AB - BACKGROUND: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) have been reported to be associated with delayed expression of hypertrophic cardiomyopathy (HCM) and a relatively good prognosis. PURPOSE: The aim of this study was to evaluate clinical manifestations in patients with familial HCM caused by a novel nonsense mutation, S297X, in MYBPC3. METHODS: We analyzed the sarcomere protein genes in 93 probands with HCM. RESULTS: The nonsense mutation S297X in MYBPC3 was present in nine subjects from two unrelated families. Eight of those nine subjects with this mutation were found to be phenotype-positive and the remaining individual was not affected phenotypically. The age range at diagnosis was 9-75 years. There was no family history of sudden death in either family. At presentation, there were various left ventricular hypertrophy (LVH) patterns, including Maron type III hypertrophy from the LV base to apex, hypertrophy confined to the anterolateral wall at the basal LV wall. Two patients showed a significant LV outflow tract gradient and one patient showed intra-right ventricular obstruction. During follow-up, one patient was repeatedly hospitalized for the treatment of heart failure after development of paroxysmal atrial fibrillation at the age of 86 years and the remaining eight subjects were in relatively stable condition and did not require hospitalization for the treatment of HCM-related events. CONCLUSION: The novel mutation S297X in MYBPC3 causes HCM in a broad range of ages and heterogeneous clinical manifestations, though the clinical course in patients with this mutation seems to be benign. PMID- 20350522 TI - Relation between functional stenosis and tissue characterization of intermediate coronary plaques in patients with stable coronary heart disease. AB - BACKGROUND: Tissue characteristics of coronary plaques can be evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), while fractional flow reserve (FFRmyo) is an index of functional coronary stenosis. We assessed the relation between functional stenosis and the characteristics of plaque tissue using FFRmyo and IB-IVUS. METHODS AND RESULTS: A total of 17 lesions with 75% stenosis assessed visually by coronary angiography from 17 stable angina patients (64.2+/-9.1 years old, 11 males) were studied. IB-IVUS was evaluated in the most stenotic cross-sectional area. Using commercially available software, coronary plaques were assessed for calcification (CA), fibrosis (F), and lipid pool (LP). Lesions were localized in the left anterior descending artery in 11 patients, the left circumflex in 3, and the right coronary artery in 3. On quantitative coronary angiography, the percent diameter stenosis (%DS) was 60.5+/-7.3%. Plaque burden was 71.4+/-9.1%, FFRmyo was 0.74+/-0.13. The tissue component of the plaques was: CA(%), 3.0+/-2.4%; F(%), 60.5+/-9.6%; LP(%), 37.2+/-11.0%. Significant correlation was not observed between %DS or plaque burden and FFRmyo, structural stenosis and plaque characterization, nor between CA(%) and FFRmyo. There was a positive correlation between F(%) and FFRmyo (r=0.62, p<0.01) and a negative correlation between LP(%) and FFRmyo (r=-0.52, p<0.05). CONCLUSION: Our findings indicate that the tissue characteristics of coronary plaques in intermediate lesion affect functional stenosis. PMID- 20350523 TI - Design and rationale of a study in Asia of atorvastatin pretreatment in patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes. AB - BACKGROUND: Studies in Western populations have shown the benefits of pretreatment with atorvastatin in preventing cardiovascular events in patients, including those with acute coronary syndromes (ACS), undergoing percutaneous coronary intervention (PCI). However, data concerning the value of such therapy in Asian patients are limited. The primary objective of the present study is to evaluate the efficacy of atorvastatin in reducing cardiovascular outcomes in Asian patients with non-ST-segment elevation (NSTE)-ACS following hospital admission for early PCI (within 72 h of the onset of symptoms). Secondary objectives are to assess the effects of atorvastatin on cardiac biomarker levels, and the safety and tolerability profile of atorvastatin. METHODS: This study is a prospective, multicenter, open-label trial designed to enroll 350 statin-naive patients with NSTE-ACS scheduled for PCI in China and the Republic of Korea. Patients are randomized to either usual care or atorvastatin treatment groups, with patients in both treatment groups receiving usual care including atorvastatin 40 mg/day for 30 days post-PCI. Patients in the atorvastatin group receive additional doses of atorvastatin 80 mg at 12 h pre-PCI and 40 mg at 2 h pre-PCI. The primary end point is the incidence of major adverse cardiac events (death, myocardial infarction, and target vessel revascularization) at 30 days post-PCI. CONCLUSIONS: The present study will provide valuable insights into whether the benefits of atorvastatin pretreatment extend to Asian patients with ACS undergoing interventions. Enhanced treatment of these patients will be an important contribution towards alleviating the increasing burden of cardiovascular disease in Asian countries. PMID- 20350524 TI - Estimated glomerular filtration rate is an independent predictor for mortality of patients with acute heart failure. AB - BACKGROUND: Heart failure is a major public health problem in developed countries including Japan, therefore it is important to estimate the future risk in patients with heart failure. Recently, it has been reported that chronic kidney disease (CKD) is an independent predictor for mortality in chronic heart failure. However, it is unknown whether CKD is an independent predictor for mortality in acute heart failure. We retrospectively investigated the relationship between estimated glomerular filtration rate (eGFR) on admission for acute heart failure and long-term mortality. METHODS: We analyzed 194 patients who were admitted for acute heart failure from January, 2002 to February, 2005. Patients were divided into two groups, high-eGFR group (eGFR <60 ml/min, n=75) and low-eGFR group (eGFR > or =60 ml/min, n=119). eGFR was calculated by equation of MDRD (modification of the diet in renal disease) study. eGFR level <60 ml/min/1.73 m(2) is impaired renal function according to the guidelines of the Japanese Society of Nephrology and of the National Kidney Foundation. Serum B-type natriuretic peptide (BNP) level and left ventricular ejection fraction (LVEF), anemia, age, gender, and etiology of heart failure were also evaluated. Median observation period was 609 days (range: 30-1627). Mean age was 69 years and 138 patients were male. RESULTS: Median eGFR on admission was 74.2 ml/min (range: 5.48-238.7), median BNP level was 840 pg/ml (range: 200-4800), and median LVEF was 36% (range: 11-81%). Forty two percent of patients had eGFR <60 ml/min of eGFR at the time of coronary care unit admission. Patients with low-eGFR had a significantly lower mortality rate by Kaplan-Meier analysis (log rank test, p=0.013). By Cox's proportional-hazard analysis, eGFR was an independent factor for long-term mortality of acute heart failure (p=0.039). CONCLUSIONS: Lower eGFR at the time of admission could be an independent predictor for mortality of acute heart failure. PMID- 20350525 TI - Vibrio harveyi hemolysin induces ultrastructural changes and apoptosis in flounder (Paralichthys olivaceus) cells. AB - Vibrio harveyi hemolysin (VHH) is considered a major pathogenic virulence factor to fish. However, the VHH active-site mutant has lost all hemolytic and phospholipase activities as well as pathogenicity. In this study, the effect of VHH on erythrocytes and a gill cell line from flounder was elucidated. Erythrocyte membranes formed thin tubular protrusions immediately after exposure to VHH, and membrane corrugations were evident after extended incubation. In contrast, the mutant VHH did not induce any gross morphological changes. With VHH treated FG-9307 cells, a cell line derived from flounder gill, destruction of organelles and formation of features resembling apoptotic bodies were observed. Immunogold staining showed that a large amount of VHH was deposited on the membranes and membrane debris of erythrocytes and FG-9307 cells after treatment with VHH. Apoptotic features, such as chromatin condensation and apoptotic bodies, were observed in VHH-treated FG-9307 cells using DAPI staining. Moreover, cell cycle analysis showed that VHH increased the proportion of cells in G1 phase. In addition, VHH significantly increased the percentage of apoptosis, the number of TUNEL positive apoptotic cells, and caspase-3 activity in FG-9307 cells when compared with the untreated controls. These data suggested that VHH killed the cells through apoptosis via the caspase activation pathway. PMID- 20350526 TI - Peptides panned from a phage-displayed random peptide library are useful for the detection of Bacillus anthracis surrogates B. cereus 4342 and B. anthracis Sterne. AB - Recent use of Bacillus anthracis as a bioweapon has highlighted the need for a sensitive monitoring system. Current bacterial detection tests use antibodies as bio-molecular recognition elements which have limitations with regard to time, specificity and sensitivity, creating the need for new and improved cost effective high-affinity detection probes. In this study, we screened a commercially available bacteriophage-displayed random peptide library using Bacillus cereus 4342 cells as bait to identify peptides that could be used for detection of Bacillus. The method enabled us to identify two 12-amino acid consensus peptide sequences that specifically bind to B. cereus 4342 and B. anthracis Sterne, the nonpathogenic surrogates of B. anthracis strain. The two Bacillus-binding peptides (named BBP-1 and BBP-2) were synthesized with biotin tag to confirm their binding by four independent detection assays. Dot-blot analysis revealed that the peptides bind specifically to B. cereus 4342 and B. anthracis Sterne. Quantitative analysis of this interaction by ELISA and fluorometry demonstrated a detection sensitivity of 10(2) colony forming U/ml (CFU/ml) by both assays. When the peptides were used in combination with Qdots, the sensitivity was enhanced further by enabling detection of even a single bacterium by fluorescence microscopy. Immunoblot analysis and protein sequencing showed that BBP-1 and BBP-2 bound to the S-layer protein of B. anthracis Sterne. Overall, our findings validate the usefulness of synthetic versions of phage derived peptides in combination with Qdot-liquid nanocrystals as high sensitivity bioprobes for various microbial detection platforms. PMID- 20350527 TI - Glucose intolerance and diabetes following antigen-specific insulitis in diabetes susceptible "humanized" transgenic mice. AB - The genetic contribution of antigen-presenting molecules and the environmental ignition of an antigen-specific immune attack to pancreatic beta-cells define autoimmune diabetes. We focused here on generating an antigen-specific model of autoimmune diabetes in humanized double-transgenic mice carrying antigen presenting HLA-DQ8 diabetes-linked haplotype and expressing human autoantigen GAD65 in pancreatic beta-cells using a relatively diabetes-susceptible strain of mice. Double transgenic (DQ8-GAD65) mice and controls were immunized with cDNA encoding human GAD65 in adenoviral vectors and monitored for glucose intolerance and diabetes. Human-GAD65 immunization induced insulitis, glucose intolerance and diabetes in double-transgenic mice, while controls were insulitis free and glucose tolerant. Glucose intolerance 10 weeks post-immunization was followed by diabetes later on in most animals. Destructive insulitis characterized by inflammation and apoptosis correlated with the diabetes outcome. Humoral immune responses to hGAD65 were sustained in mice with diabetes while transient in non responders. Insulitis was massive in mice with diabetes while mild in non responders by the end of the study. Our results show for the first time the occurrence of antigen-specific induced insulitis, impaired glucose homeostasis and diabetes after immunization with a clinically relevant, human autoantigen in the context of HLA-DQ8 diabetes-susceptibility transgenes and human GAD65 expression in beta-cells. This animal model will facilitate studies of mechanisms of disease involved in development of autoimmunity to GAD65 in the context of HLA DQ8. Furthermore, this model would be ideal for testing therapeutic strategies aimed at preventing human beta-cell loss and/or restoring function in the setting of autoimmune diabetes. PMID- 20350528 TI - Characterization of two M17 family members in Escherichia coli, Peptidase A and Peptidase B. AB - Escherichia coli encodes two aminopeptidases belonging to the M17 family: Peptidase A (PepA) and Peptidase B (PepB). To gain insights into their substrate specificities, PepA or PepB were overexpressed in Delta pepN, which shows greatly reduced activity against the majority of amino acid substrates. Overexpression of PepA or PepB increases catalytic activity of several aminopeptidase substrates and partially rescues growth of Delta pepN during nutritional downshift and high temperature stress. Purified PepA and PepB display broad substrate specificity and Leu, Lys, Met and Gly are preferred substrates. However, distinct differences are observed between these two paralogs: PepA is more stable at high temperature whereas PepB displays broader substrate specificity as it cleaves Asp and insulin B chain peptide. Importantly, this strategy, i.e. overexpression of peptidases in Delta pepN and screening a panel of substrates for cleavage, can be used to rapidly identify peptidases with novel substrate specificities encoded in genomes of different organisms. PMID- 20350529 TI - N-Formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam, KNK437 induces caspase-3 activation through inhibition of mTORC1 activity in Cos-1 cells. AB - The mammalian target of rapamycin complex 1 (mTORC1: mTOR-raptor interaction) and heat shock protein 70 (Hsp70) regulate various cellular processes and are crucial for the progression of many cancers and metabolic diseases. In the recent study, we reported that interaction of Hsp70 with tuberous sclerosis complex 1 (TSC1) regulated apoptosis. This study was designed to elucidate the underlying mechanism in Cos-1 cells. Here, we show that N-formyl-3,4-methylenedioxy benzylidene-gamma-butyrolaetam (KNK437), which inhibits the expression level of Hsp70, abrogated phosphorylation of mTOR and S6K in response to insulin, and inhibited mTORC1 activity via disruption of an interaction between mTOR and raptor. In addition, KNK437 did not alter TSC1/2 complex formation. Furthermore, KNK437 inhibited the mTOR-raptor interaction on the outer membrane of the mitochondria and triggered caspase-3 activation. A reduction in the level of Hsp70 could result in the inhibition of the mTORC1 signaling pathway, thereby inducing apoptosis. PMID- 20350530 TI - A novel fluorescent timer based on bicistronic expression strategy in Caenorhabditis elegans. AB - Fluorescent timers are useful tools for studying the spatial and temporal cellular or molecular events. Based on the trans-splicing mechanism in Caenorhabditis elegans, we constructed a "fluorescent timer" through bicistronic expression of two fluorescent proteins with different maturation times. When used in vivo, this "timer" changes its color over time and therefore can be used to monitor the activity of the targeted promoters in C. elegans. Using this "timer", we have successfully traced the time-dependent activity of myo-3 promoter which drives expression in body wall muscle and vulval muscle. We found that the myo-3 promoter started to be active about 7 h after egg-laying and sustained its activity in the following hatching process. We have also determined the myo-3 promoter activity during larval development by this "timer". We anticipate that more new "fluorescent timers" with variable time-resolution could be designed by bicistronic expression of different fluorescent protein pairs. PMID- 20350531 TI - Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. AB - Leukemia stem cells are known to exhibit multidrug resistance by expression of ATP-binding cassette (ABC) transporters which constitute transmembrane proteins capable of exporting a wide variety of chemotherapeutic drugs from the cytosol. We show here that human promyeloblastic leukemia KG-1a cells exposed to the histone deacetylase inhibitor phenylbutyrate resemble many characteristics of leukemia stem cells, including expression of functional ABC transporters such as P-glycoprotein, BCRP and MRP8. Consequently, KG-1a cells display resistance to the induction of apoptosis by various chemotherapeutic drugs. Resistance to apoptosis induction by chemotherapeutic drugs can be reversed by cyclosporine A, which effectively inhibits the activity of P-glycoprotein and BCRP, thus demonstrating ABC transporter-mediated drug resistance in KG-1a cells. However, KG-1a are highly sensitive to apoptosis induction by salinomycin, a polyether ionophore antibiotic that has recently been shown to kill human breast cancer stem cell-like cells and to induce apoptosis in human cancer cells displaying multiple mechanisms of drug and apoptosis resistance. Whereas KG-1a cells can be adapted to proliferate in the presence of apoptosis-inducing concentrations of bortezomib and doxorubicin, salinomycin does not permit long-term adaptation of the cells to apoptosis-inducing concentrations. Thus, salinomycin should be regarded as a novel and effective agent for the elimination of leukemia stem cells and other tumor cells exhibiting ABC transporter-mediated multidrug resistance. PMID- 20350532 TI - A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus. AB - Human respiratory syncytial virus (RSV), for which no clinically approved vaccine is available yet, is globally a serious pediatric pathogen of the lower respiratory tract. Several approaches have been used to develop vaccines against RSV, but none of these have been approved for use in humans. An efficient vaccine enhancing strategy for RSV is still urgently needed. We found previously that oral SL7207/pcDNA3.1/F and intranasal FGAd/F were able to induce an effective protective immune response against RSV. The heterologous prime-boost immunization regime has been reported recently to be an efficient vaccine-enhancing strategy. Therefore, we investigated the ability of an oral SL7207/pcDNA3.1/F prime and intranasal (i.n.) FGAd/F boost regimen to generate immune responses to RSV. The SL7207/pcDNA3.1/F prime-FGAd/F boost regimen generated stronger RSV-specific humoral and mucosal immune responses in BALB/c mice than the oral SL7207/pcDNA3.1/F regimen alone, and stronger specific cellular immune responses than the i.n. FGAd/F regimen alone. Histopathological analysis showed an increased efficacy against RSV challenge by the heterologous prime-boost regimen. These results suggest that such a heterologous prime-boost strategy can enhance the efficacy of either the SL7207 or the FGAd vector regimen in generating immune responses in BALB/c mice. PMID- 20350533 TI - DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma. AB - DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy. PMID- 20350534 TI - Resveratrol-mediated reversal of doxorubicin resistance in acute myeloid leukemia cells via downregulation of MRP1 expression. AB - Chemo-resistance to anti-cancer drugs is a major obstacle in efforts to develop a successful treatment of acute myeloid leukemia (AML). In this study, we investigate whether resveratrol, a common ingredient in a broad variety of fruits and vegetables, can reverse drug resistance in AML cells. Three doxorubicin resistant AML cell lines (AML-2/DX30, AML-2/DX100, AML-2/DX300) were prepared via long-term exposure to doxorubicin for more than 3 months. DNA microarray analysis demonstrated that many genes were differentially expressed in the resistant cells, as compared with the wild type AML-2/WT cells. In particular, the expression level of the MRP1 gene was significantly increased in the AML-2/DX300 cells, as compared to that detected in AML-2 cells. Importantly, the resveratrol was shown not only to induce cell growth arrest and apoptotic death in doxorubicin-resistant AML cells, but was also shown to downregulate the expression of an MRP1 gene. Furthermore, resveratrol treatment induced a significant increase in the uptake of 5(6)-carboxyfluorescein diacetate, a MRP1 substrate, into the doxorubicin-resistant AML-2/DX300 cells. The results of this study show that resveratrol may facilitate the cellular uptake of doxorubicin via an induced downregulation of MRP1 expression, and also suggest that it may prove useful in overcoming doxorubicin resistance, or in sensitizing doxorubicin resistant AML cells to anti-leukemic agents. PMID- 20350536 TI - When frequencies never synchronize: the golden mean and the resting EEG. AB - The classical frequency bands of the EEG can be described as a geometric series with a ratio (between neighbouring frequencies) of 1.618, which is the golden mean. Here we show that a synchronization of the excitatory phases of two oscillations with frequencies f1 and f2 is impossible (in a mathematical sense) when their ratio equals the golden mean, because their excitatory phases never meet. Thus, in a mathematical sense, the golden mean provides a totally uncoupled ('desynchronized') processing state which most likely reflects a 'resting' brain, which is not involved in selective information processing. However, excitatory phases of the f1- and f2-oscillations occasionally come close enough to coincide in a physiological sense. These coincidences are more frequent, the higher the frequencies f1 and f2. We demonstrate that the pattern of excitatory phase meetings provided by the golden mean as the 'most irrational' number is least frequent and most irregular. Thus, in a physiological sense, the golden mean provides (i) the highest physiologically possible desynchronized state in the resting brain, (ii) the possibility for spontaneous and most irregular (!) coupling and uncoupling between rhythms and (iii) the opportunity for a transition from resting state to activity. These characteristics have already been discussed to lay the ground for a healthy interplay between various physiological processes (Buchmann, 2002). PMID- 20350535 TI - BRAF as therapeutic target in melanoma. AB - BRAF is a member of the RAF kinase family, which acts in the ERK/MAP kinase pathway, a signalling cascade that regulates cellular proliferation, differentiation and survival. Single point mutations can turn BRAF into an oncogene, but there appears to be a cell type/tumour specific relevance for BRAF kinase-activating mutations, since they are found predominantly in cutaneous melanoma. With the success of targeting other oncogenic kinases such as BCR-ABL, KIT or members of the epidermal-growth factor receptor (EGFR) family in other cancers, the expectations were high when the first RAF kinase-targeting drug (sorafenib) reached clinical trials. However, disappointingly the first studies using sorafenib in melanoma patients did not show the anticipated single agent efficacy. More recently, the resolution of the BRAF crystal structure has led to the development of better, more specific BRAF inhibitors such as the Plexxikon compound, PLX4032, which induced a dramatic response rate in phase I trials, validating BRAF as a clinically relevant target. In addition, our understanding of melanoma biology and the role BRAF is playing therein has improved significantly. The complexity in the ERK/MAP kinase pathway including important feedback mechanisms has been dissected, and the relevance of cross-talks with other signalling pathways has been revealed, suggesting strategies for the design of improved, more efficient combinatorial therapies. This review highlights the relevance of BRAF and the ERK/MAP kinase pathway for melanoma cell biology and discusses some of the recent advances in both, the understanding of BRAF function in melanoma and the development of improved BRAF targeting inhibitors. PMID- 20350537 TI - Interaction study of two diterpenes, cryptotanshinone and dihydrotanshinone, to human acetylcholinesterase and butyrylcholinesterase by molecular docking and kinetic analysis. AB - Alzhemier's disease (AD) is a common form of dementia in the ageing population which is characterized by depositions of amyloids and a cholinergic neurotransmission deficit in the brain. Current therapeutic intervention for AD is primarily based on the inhibition of brain acetylcholinesterase (AChE) to restore the brain acetylcholine level. Cryptotanshinone (CT) and dihydrotanshinone (DT) were diterpenoids extracted from Salvia miltiorrhiza Bge. having anti-cholinesterase activity. Here we characterized the inhibition property of these two diterpenoids towards human AChE and butyrylcholinesterase (BChE). Both CT and DT were found to be mixed non-competitive inhibitors for human AChE and an uncompetitive inhibitor for human BChE. The docking analyses of CT and DT into the active sites of both cholinesterases indicate that they interact with the allosteric site inside the active-site gorge mainly by hydrophobic interactions. PMID- 20350538 TI - NT-proBNP levels in systemic sclerosis: association with clinical and laboratory abnormalities. AB - OBJECTIVE: To identify factors related to NT-proBNP levels in systemic sclerosis (SSc). DESIGN AND METHODS: NT-proBNP was measured in 119 patients with SSc and 20 controls. Patients with transtricuspid gradient (TG) > or =36 mm Hg or > or =31 mmHg plus dyspnea were considered to have suspected systemic sclerosis-associated pulmonary arterial hypertension (SScPAH). RESULTS: Increasing age, NYHA functional class, skin score, history of systemic arterial hypertension (SAH), anticentromere antibodies, diastolic dysfunction, reduced pulmonary diffusing capacity, and TG were positively associated with NT-proBNP. In multivariable linear regression, TG, age, and SAH were independently associated to NT-proBNP levels. An ROC curve analysis (with an area under the curve of 0.89, 95% CI: 0.83 0.95) suggested a cutoff of 157.8pg/mL to identify patients with suspected SScPAH, presenting a sensitivity of 100% (78.1-100) and specificity of 72.3% (62.3-80.5). CONCLUSIONS: NT-proBNP levels are related to clinical and laboratory abnormalities in SSc. The results indicate that NT-proBNP may be a useful tool in the evaluation of SScPAH. PMID- 20350539 TI - Comparing sugar type supplementation for cryopreservation of boar semen in egg yolk based extender. AB - Cryopreservation of boar semen is still considered suboptimal due to lower fertility when compared to fresh semen. The aim of this study was to evaluate the effects of the addition of different sugars (lactose, trehalose and glucose) on boar spermatozoa cryopreserved in an egg yolk based extender. Ejaculates were collected from a boar previously selected and semen samples were processed using the straw freezing procedure. In experiment 1, subsamples of semen were frozen in three different extenders: recommended lactose egg yolk extender (LEY); trehalose egg yolk extender (TEY) and glucose egg yolk extender (GEY). Sperm quality was assessed for motility, viability, acrosome integrity and hypoosmotic swelling test response upon collection, after freezing and thawing and then every hour for 3h. Results showed that total motility at 1 and 3h, progressive motility at 3h, positive hypoosmotic response at 2 and 3h and acrosome integrity at all times were significantly improved when trehalose was added to the extender. In experiment 2, sugar influence was also demonstrated in vitro fertilization. A total of 1691 oocytes were in vitro matured and inseminated with frozen-thawed sperm at 2000:1 sperm:oocyte ratio and coincubated for 6h. Presumptive zygotes were cultured in NCSU-23 medium to assess fertilization parameters and embryo development. Both penetration and monospermy rates were significantly higher for trehalose frozen semen. A significant increase was observed in efficiency and blastocyst formation rates from TEY to the other groups. Our results demonstrated that trehalose extender enhances spermatozoa viability and its in vitro fertilization parameters in boar ejaculates with good sperm freezability. Further studies are necessary to assess the impact of sugars on the entire population. PMID- 20350540 TI - Nonmuscle myosin IIB, a sarcomeric component in the extraocular muscles. AB - Extraocular muscles (EOMs) are categorized as skeletal muscles; however, emerging evidence indicates that their gene expression profile, metabolic characteristics and functional properties are significantly different from the prototypical members of this muscle class. Gene expression profiling of developing and adult EOM suggest that many myofilament and cytoskeletal proteins have unique expression patterns in EOMs, including the maintained expression of embryonic and fetal isoforms of myosin heavy chains (MyHC), the presence of a unique EOM specific MyHC and mixtures of both cardiac and skeletal muscle isoforms of thick and thin filament accessory proteins. We demonstrate that nonmuscle myosin IIB (nmMyH IIB) is a sarcomeric component in approximately 20% of the global layer fibers in adult rat EOMs. Comparisons of the myofibrillar distribution of nmMyHC IIB with sarcomeric MyHCs indicate that nmMyH IIB co-exists with slow MyHC isoforms. In longitudinal sections of adult rat EOM, nmMyHC IIB appears to be restricted to the A-bands. Although nmMyHC IIB has been previously identified as a component of skeletal and cardiac sarcomeres at the level of the Z-line, the novel distribution of this protein within the A band in EOMs is further evidence of both the EOMs complexity and unconventional phenotype. PMID- 20350541 TI - Transforming growth factor-beta in the chicken fundal layers: an immunohistochemical study. AB - In the chicken model of myopia, it has first been shown that imposing defocus to the retina results in active remodelling of the sclera which, in turn, results in axial length changes of the eye. Transforming growth factor-beta (TGF-beta) is one of the scleral growth modulators but its cellular localization in the fundal layers, colocalization and function are not well known. The aim of the current study was to investigate the cellular distribution of the three isoforms TGF beta1, 2 and 3 by immunohistochemical labelling. Furthermore, the effects of visual experience that induces refractive errors on TGF-beta2 labelling were examined. Transversal cryostat sections of the fundal layers were analyzed by indirect immunofluorescent labelling and cell counts. Visual experience was changed by having the chicks wear either diffusers, or positive or negative lenses of 7D power in front of the right eyes for various periods of time. Left eyes served as uncovered controls. All TGF-beta isoforms were localized in both scleral layers. In choroid, diffuse labelling of all isoforms was found. In retina, TGF-beta1 and 3 were detected in bipolar, amacrine and ganglion cells and TGF-beta2 in amacrine and ganglion cells. To further characterize these cells, double-labelling with known amacrine and bipolar cell markers was performed (calbindin, cellular retinoic acid binding protein (CRABP), Islet1, Lim3 and protein kinase C (PKC)). TGF-beta1, 2 and 3 could be colocalized with calbindin and CRABP in single amacrine cells. TGF-beta1-positive bipolar cells were immunoreactive to Lim3. TGF-beta1 and 3 were never colocalized with PKC in bipolar cells. Also, colocalization with peptides known to be involved in myopia development in chicks, such as glucagon, or vasointestinal polypeptide and the key enzyme for dopamine synthesis, tyrosine hydroxylase, was not observed. Lenses or diffusers, worn by the chicks for various periods of time, had no effect on TGF-beta2 immunoreactivity in choroid or sclera, or on the number of TGF-beta2 (active and latent form) expressing amacrine cells. This result did not change when the two identified populations of TGF-beta2 expressing amacrine cells (one calbindin-positive and the other CRABP-positive) were separately considered. Also no modulation was seen in choroid, although an earlier study had found changes in TGF-beta2 mRNA after lens treatment. The lack of any visually-induced changes in retina or choroid suggests that TGF-beta may not represent a key molecule in the retino-choroidal signalling cascade although it has previously been shown to have a primary role in scleral remodelling. PMID- 20350543 TI - Evolution of 11beta-hydroxysteroid dehydrogenase-type 1 and 11beta-hydroxysteroid dehydrogenase-type 3. AB - A key regulator of glucocorticoid action is 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyzes the conversion of cortisone to cortisol, the biologically active glucocorticoid. 11beta-HSD1 is a paralog of 11beta-HSD3, whose physiological function remains unclear. As reported here, 11beta-HSD3 has orthologs in sea urchin, amphioxus and Ciona, while 11beta-HSD1 first appears in sharks. Thus, 11beta-HSD3 arose before the evolution of glucocorticoid signaling, suggesting different ancestral function(s) for 11beta-HSD3. Four perplexing findings arise from this evolutionary analysis: (1) 11beta-HSD1 is not present in a ray-finned fish genome, (2) zebrafish and fathead minnow contain two isoforms of 11beta-HSD3; (3) neither rat nor mouse contain 11beta-HSD3 and (4) amphioxus contains 16 11beta-HSD3 paralogs. PMID- 20350542 TI - Entamoeba histolytica: soluble and membrane-associated neutral sphingomyelinase-C and other unidentified esterase activity. AB - Sphingomyelinase (SMase) activity was measured in Entamoeba histolytica particulate and soluble subcellular fractions. The effects on SMase of incubation time, total protein concentration, pH, and several divalent cations were determined. SMase-C and other unidentified esterase activity were detected in soluble and particulate fractions. SMase-C was 94.5-96.0% higher than the unidentified esterase activity. Soluble and insoluble SMase-C specific activities increased with protein dose and incubation time. Soluble and insoluble SMase-C activities were maximum at pH 7.5 and were dependent on Mg(2+), Mn(2+), or Co(2+), and inhibited by Zn(2+), Hg(2+), Ca(2+), and EDTA. SMase-C was active in the pH range of 3-10 and its maximum activity was at pH 7.5. The soluble and insoluble SMases have remarkably similar physicochemical properties, strongly suggesting that E. histolytica has just one isoform of neutral SMase-C that had not been described before and might be essential for E. histolytica metabolism or virulence. PMID- 20350544 TI - L-lactate generates hydrogen peroxide in purified rat liver mitochondria due to the putative L-lactate oxidase localized in the intermembrane space. AB - In order to ascertain whether and how mitochondria can produce hydrogen peroxide (H(2)O(2)) as a result of L-lactate addition, we monitored H(2)O(2) generation in rat liver mitochondria and in submitochondrial fractions free of peroxisomal and cytosolic contamination. We found that H(2)O(2) is produced independently on the respiratory chain with 1:1 stoichiometry with pyruvate, due to a putative flavine dependent L-lactate oxidase restricted to the intermembrane space. The L-lactate oxidase reaction shows a hyperbolic dependence on L-lactate concentration and is inhibited by NAD(+) in a competitive manner, being the enzyme different from the L-lactate dehydrogenase isoenzymes as shown by their pH profiles. PMID- 20350545 TI - Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max. AB - Triterpene saponins are a diverse group of compounds with a structure consisting of a triterpene aglycone and sugars. Identification of the sugar-transferase involved in triterpene saponin biosynthesis is difficult due to the structural complexity of triterpene saponin. Two glycosyltransferases from Glycine max, designated as GmSGT2 and GmSGT3, were identified and characterized. In vitro analysis revealed that GmSGT2 transfers a galactosyl group from UDP-galactose to soyasapogenol B monoglucuronide, and that GmSGT3 transfers a rhamnosyl group from UDP-rhamnose to soyasaponin III. These results suggest that soyasaponin I is biosynthesized from soyasapogenol B by successive sugar transfer reactions. PMID- 20350546 TI - Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring. AB - Endometriosis is a chronic gynecological disease characterized by the growth of endometrial tissue outside the uterine cavity. Exposure to endocrine disruptors during critical period of development causes long-lasting effects, being the genital system one of the targets. This study describes the effects on female genital system caused by developmental exposure to the endocrine-disrupting chemical bisphenol A (BPA) during pre- and peri-natal development in mice. To this end, timed pregnant Balb-C mice were treated from day 1 of gestation to 7 days after delivery with BPA (100, or 1000 microg/kg/day). After delivery, pups were held for 3 months; then, pelvic organs were analyzed in their entirety and livers of both pups and moms were studied for the presence of BPA. We found in the adipose tissue surrounding the genital tracts of a consistent number of treated animals, endometriosis-like structure with the presence of both glands and stroma and expressing both estrogen receptor and HOXA-10. Moreover, cystic ovaries, adenomatous hyperplasia with cystic endometrial hyperplasia and atypical hyperplasia were significantly more frequent in treated animals respect to the controls. Finally, BPA was found in the livers of exposed moms and female offspring. In conclusion, we describe for the first time an endometriosis-like phenotype in mice, elicited by pre-natal exposition to BPA. This observation may induce to thoroughly reconsider the pathogenesis and treatment of endometriosis, considering the high incidence of endometriosis and the problems caused by associated infertility. PMID- 20350547 TI - Changes in prolactin mRNA levels during downstream migration of the amphidromous teleost, ayu Plecoglossus altivelis. AB - Changes in mRNA levels of prolactin (PRL) during seaward migration and after experimental transfer from fresh water (FW) to seawater (SW) were examined in larvae of the amphidromous fish, ayu Plecoglossus altivelis. In the field study, ayu larvae caught in the surf zone showed lower levels of PRL mRNA than those in the river, while growth hormone (GH) levels showed no significant change. Decrease in PRL gene transcription was also observed 24h after direct transfer from FW to SW, whereas there was no significant influence of water temperature. On the other hand, there was no significant change in GH mRNA levels in relation to SW transfer or environmental temperature. In a raceway with a vertical salinity gradient, PRL mRNA levels of ayu larvae showed a significant reduction during spontaneous migration from FW to SW, which mimicked the results from the field observation and the transfer experiment, and then a gradual increase during the course of development. Whole body water and sodium contents of larvae in a salinity gradient were stable during migration to SW. Results in this study indicated the importance of regulation of PRL gene expression in the downstream migration and acclimation to SW during the early development of ayu. PMID- 20350548 TI - Activation of the chicken gonadotropin-inhibitory hormone receptor reduces gonadotropin releasing hormone receptor signaling. AB - Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic peptide from the RFamide peptide family that has been identified in multiple avian species. Although GnIH has clearly been shown to reduce LH release from the anterior pituitary gland, its mechanism of action remains to be determined. The overall objectives of this study were (1) to characterize the GnIH receptor (GnIH-R) signaling pathway, (2) to evaluate potential interactions with gonadotropin releasing hormone type III receptor (GnRH-R-III) signaling, and (3) to determine the molecular mechanisms by which GnIH and GnRH regulate pituitary gonadotrope function during a reproductive cycle in the chicken. Using real-time PCR, we showed that in the chicken pituitary gland, GnIH-R mRNA levels fluctuate in an opposite manner to GnRH-R III, with higher and lower levels observed during inactive and active reproductive stages, respectively. We demonstrated that the chicken GnIH-R signals by inhibiting adenylyl cyclase cAMP production, most likely by coupling to G(alphai). We also showed that this inhibition is sufficient to significantly reduce GnRH-induced cAMP responsive element (CRE) activation in a dose-dependent manner, and that the ratio of GnRH/GnIH receptors is a significant factor. We propose that in avian species, sexual maturation is characterized by a change in GnIH/GnRH receptor ratio, resulting in a switch in pituitary sensitivity from inhibitory (involving GnIH) to stimulatory (involving GnRH). In turn, decreasing GnIH-R signaling, combined with increasing GnRH-R-III signaling, results in significant increases in CRE activation, possibly initiating gonadotropin synthesis. PMID- 20350550 TI - Schistosoma mansoni Polo-like kinase 1: A mitotic kinase with key functions in parasite reproduction. AB - Polo-like kinases (Plks) are conserved regulators of mitosis. In mammals, Plk1 is over-expressed in a wide range of tumour cells and constitutes a valuable target for anti-cancer therapy. This work presents the characterisation of the Plk1 homologue (SmPlk1) of Schistosoma mansoni, a trematode responsible for schistosomiasis, one of the most important parasitic diseases, second only to malaria. The intense levels of disease transmission and the severity of pathologies are the consequences of the exceptional reproductive activity of schistosomes, in which Plks may play a decisive role. Structural and functional analyses of SmPlk1 have demonstrated its homology with other Plk1 members and its conserved function in mitotic processes. Activation of SmPlk1 was shown to be dependent on phosphorylation of its conserved threonine residue (T(182)) and the ability of active SmPlk1 to induce mitosis was demonstrated in the Xenopus oocyte model. SmPlk1 transcripts were detected abundantly in parasite stages containing a high amount of germinal cells. A potential role of SmPlk1 in mitosis and/or meiosis in schistosomes was supported by the in situ detection of SmPlk1 transcripts in female vitelline cells and oocytes as well as in male spermatocytes. Several Plk inhibitors were shown to inhibit SmPlk1 activity in Xenopus oocytes, and BI 2536 (the first-in-class prototype Plk1 inhibitor) induced in vitro dramatic alterations in schistosome gonads, which affected oogenesis and spermatogenesis. These results indicate a major role for SmPlk1 in parasite reproduction and suggest its importance as a potential new target against schistosomiasis. PMID- 20350551 TI - Contributions of immune responses to developmental resistance in Lymantria dispar challenged with baculovirus. AB - How the innate immune system functions to defend insects from viruses is an emerging field of study. We examined the impact of melanized encapsulation, a component of innate immunity that integrates both cellular and humoral immune responses, on the success of the baculovirus Lymantria dispar multiple nucleocapsid nucleopolyhedrovirus (LdMNPV) in its host L. dispar. L. dispar exhibits midgut-based and systemic, age-dependent resistance to LdMNPV within the fourth instar; the LD(50) in newly molted larvae is approximately 18-fold lower than in mid-instar larvae (48-72h post-molt). We examined the role of the immune system in systemic resistance by measuring differences in hemocyte immunoresponsiveness to foreign targets, hemolymph phenoloxidase (PO) and FAD glucose dehydrogenase (GLD) activities, and melanization of infected tissue culture cells. Mid-instar larvae showed a higher degree of hemocyte immunoresponsiveness, greater potential PO activity (pro-PO) at the time the virus is escaping the midgut to enter the hemocoel (72h post-inoculation), greater GLD activity, and more targeted melanization of infected tissue, which correlate with reduced viral success in the host. These findings support the hypothesis that innate immune responses can play an important role in anti-viral defenses against baculoviruses and that the success of these defenses can be age dependent. PMID- 20350549 TI - Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity. AB - Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT. PMID- 20350552 TI - Discovery and effects of Texas Solenopsis invicta virus [SINV-1 (TX5)] on red imported fire ant populations. AB - Solenopsis invicta Buren (Hymenoptera: Formicidae), the red imported fire ant is native to South America but has invaded areas of the southeastern US, and parts of Southern California. The S. invicta virus-1 (SINV-1) is a positive sense, single-stranded RNA picorna-like virus that only affects Solenopsis species. The virus can infect all caste members and developmental stages. Infection of SINV-1 can result in colony collapse in less than 3 months under laboratory conditions. This study screened S. invicta colonies from Texas for the presence of SINV through Reverse Transcriptase PCR (RT-PCR). Positive samples were genetically characterized by direct sequencing and compared with known picorna-like viruses. SINV-1 was detected in ant colonies from Smith and Henderson TX counties. Amino acid sequence comparison of SINV-1 (TX5) ORF2 region showed homologies of 96% with SINV-1, 97% with SINV-1A, 17.6% with SINV-2, and 20.7% with SINV-3. In addition, SINV-1 (TX5) was compared to 18 other Dicistroviridae viruses. Ant infecting viruses may provide new approaches to suppressing these important economic pests. PMID- 20350553 TI - Using soft X-rays for a detailed picture of divalent metal binding in the nucleosome. AB - Divalent metals associate with DNA in a site-selective manner, which can influence nucleosome positioning, mobility, compaction, and recognition by nuclear factors. We previously characterized divalent metal binding in the nucleosome core using hard (short-wavelength) X-rays allowing high-resolution crystallographic determination of the strongest affinity sites, which revealed that Mn(2+) associates with the DNA major groove in a sequence- and conformation dependent manner. In this study, we obtained diffraction data with soft X-rays at the Mn(2+) absorption edge for a core particle crystal in the presence of 10 mM MnSO(4), mimicking prevailing Mg(2+) concentration in the nucleus. This provides an exceptional view of counterion binding in the nucleosome through identification of 45 divalent metal binding sites. In addition to that at the well-characterized major interparticle interface, only one other histone-divalent metal binding site is found, which corresponds to a symmetry-related counterpart on the 'free' H2B alpha1 helix C-terminus. This emphasizes the importance of the alpha-helix dipole in ion binding and suggests that the H2B motif may serve as a nucleation site in nucleosome compaction. The 43 sites associated with the DNA are characterized by (1) high-affinity direct coordination at the most electrostatically favorable major groove locations, (2) metal hydrate binding to the major groove, (3) direct coordination to phosphate groups at sites of high charge density, (4) metal hydrate binding in the minor groove, or (5) metal hydrate-divalent anion pairing. Metal hydrates are found within the minor groove only at locations displaying a narrow range of high-intermediate width and to which histone N-terminal tails are not associated or proximal. This indicates that divalent metals and histone tails can both collaborate and compete in minor groove association, which sheds light on nucleosome solubility and chromatin compaction behavior. PMID- 20350554 TI - Edaravone directly reacts with singlet oxygen and protects cells from attack. AB - AIMS: Protective effects of edaravone, an approved medicine for acute brain infarction in Japan, on cell death induced by singlet oxygen (1O2) were examined. MAIN METHOD: The 1O2 scavenging activity was examined by direct analysis of near infrared luminescence in a cell-free system and by fluorospectrometry in the presence of cells. The protective effects of edaravone on 1O2-induced cell death were examined, using rat neuronal B50 cells. Cell death was evaluated by mitochondrial respiration (MTT assay), confocal microscopy and time-lapse imaging. The chemical reaction of edaravone with 1O2 was examined by production analysis using high performance liquid chromatography (HPLC). KEY FINDINGS: When rose Bengal (RB) in D2O was irradiated by a 514nm laser beam, the signal of 1O2 was observed. Edaravone suppressed the 1O2 signal more potently than azide, a 1O2 scavenger. When B50 cells were irradiated by 525nm green light in the RB solution, production of 1O2 and induction of cell death were observed. The fluorospectrometric study and the MTT assay revealed that 100-400microM edaravone suppressed the 1O2 production and attenuated cell death in a concentration dependent manner. Confocal microscopy and the time-lapse imaging revealed that edaravone prevented the impairment of membrane integrity and the progression of cell death induced by 1O2. The HPLC study revealed that edaravone chemically reacted with 1O2 and changed another compound. SIGNIFICANCE: Since 1O2 is possibly involved in post-ischemic neuronal damage, the clinically approved curative effects of edaravone on acute brain infarction might be attributed to its potent 1O2 scavenging activity. PMID- 20350555 TI - Asymmetric regulation by estrogen at the cholinergic gene locus in differentiated NG108-15 neuronal cells. AB - AIMS: Estrogen acts as a neurogenerative and neuroprotective factor in the cholinergic system. Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are regarded as markers of cholinergic neurons. The genes coding these proteins are located at a common locus, the cholinergic gene locus. However, few details concerning activation of the locus have been obtained. We examined the effect of estrogen on the activation pattern of the locus using a cholinergic cell line. MAIN METHODS: NG108-15 neuronal cells, as a model of cholinergic neurons, were used. Dose-dependent effects of estradiol (E2) on the gene expression of ChAT and VAChT were quantitatively determined by a real-time RT-PCR. The expression of ChAT mRNA variants was qualitatively evaluated by RT PCR using specific primers. KEY FINDINGS: The expression of ChAT and VAChT mRNA was strongly enhanced with the induction of differentiation. The enhanced expression of ChAT mRNA was further increased dose-dependently by E2 (10(-10) to 10(-7)M), while that of VAChT mRNA did not respond to E2. The up-regulation of ChAT mRNA expression by E2 was abolished by co-treatment with a pure-antagonist of estrogen receptors. A qualitative analysis of ChAT mRNA variants revealed the R types, which share a common sequence with the VAChT gene, and type M ChAT mRNA to mainly be expressed, and that the appearance of these variants was not altered by E2. SIGNIFICANCE: The cholinergic gene locus in differentiated NG108-15 neuronal cells is further activated by E2, but the effect is restricted to the transcription of ChAT gene. PMID- 20350556 TI - Altered evoked gamma-band responses reveal impaired early visual processing in ADHD children. AB - Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90ms after visual stimulation in human EEG, have been assigned a pivotal role in early visual processing. In particular, they are involved in memory matching processes and are enhanced when known stimuli are processed. The current study examined whether evoked GBR patterns during early memory matching processes could be indicative of an early visual processing deficit in ADHD patients. EEG was recorded from 13 young ADHD patients as well as 13 age-matched healthy participants. Both groups performed a simple forced choice reaction task employing line drawings of either known real-world items with representations in long-term memory or physically similar unknown items without such representations. Evoked GBRs of ADHD patients did not differentiate between known and unknown items. However, in healthy children, evoked GBRs were enhanced when stimuli matched a representation stored in memory. This finding indicates disadvantages at early visual processing stages in ADHD patients: In contrast to healthy participants, ADHD children lack an early memory based classification, possibly resulting in an impaired ability to rapidly reallocate attentional resources to relevant stimuli. These findings suggest that impaired early automatic stimulus classification in ADHD patients could be involved in deficits of selective and sustained attention. PMID- 20350558 TI - Seasonal variation in testosterone and performance in males of a non-territorial lizard species. AB - The ability to perform key behaviors, particularly those associated with reproduction, has been linked to reproductive success. However, it remains unclear as to which underlying mechanisms govern variation in the performance capacities of these behaviors. Due to its ability to mediate physiological and morphological changes, the steroid hormone testosterone has been hypothesized to influence performance. This hypothesis, however, has not been tested in a broad range of taxa or mating systems. In this study, seasonal patterns of bite force and locomotor performance were quantified concurrently with circulating testosterone levels in males of a non-territorial polygynous lizard species (Aspidoscelis sexlineata). Bite force and one measure of locomotor performance were significantly greater in the breeding season than in the post-breeding season, and this seasonal variation in performance was correlated with seasonal changes in testosterone levels. These results suggest that the performance capacities of behaviors important for acquiring mating opportunities in this species are maximized during the breeding season by elevated testosterone levels. PMID- 20350557 TI - Spatial working memory deficits in GluA1 AMPA receptor subunit knockout mice reflect impaired short-term habituation: evidence for Wagner's dual-process memory model. AB - Genetically modified mice, lacking the GluA1 AMPA receptor subunit, are impaired on spatial working memory tasks, but display normal acquisition of spatial reference memory tasks. One explanation for this dissociation is that working memory, win-shift performance engages a GluA1-dependent, non-associative, short term memory process through which animals choose relatively novel arms in preference to relatively familiar options. In contrast, spatial reference memory, as exemplified by the Morris water maze task, reflects a GluA1-independent, associative, long-term memory mechanism. These results can be accommodated by Wagner's dual-process model of memory in which short and long-term memory mechanisms exist in parallel and, under certain circumstances, compete with each other. According to our analysis, GluA1(-/-) mice lack short-term memory for recently experienced spatial stimuli. One consequence of this impairment is that these stimuli should remain surprising and thus be better able to form long-term associative representations. Consistent with this hypothesis, we have recently shown that long-term spatial memory for recently visited locations is enhanced in GluA1(-/-) mice, despite impairments in hippocampal synaptic plasticity. Taken together, these results support a role for GluA1-containing AMPA receptors in short-term habituation, and in modulating the intensity or perceived salience of stimuli. PMID- 20350559 TI - The validation of an in vitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions. AB - Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay, two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a "blinded" evaluation of nine drugs associated with or without clinically identified constipation/diarrhea type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs asssessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment. PMID- 20350560 TI - Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos. AB - Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system. PMID- 20350561 TI - Functional and phenotypic effects of AhR activation in inflammatory dendritic cells. AB - Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immune suppression. Dendritic cells (DCs) are key antigen presenting cells governing T cell activation and differentiation. However, the consequences of AhR activation in DCs are not fully defined. We hypothesized that AhR activation alters DC differentiation and generates dysfunctional DCs. To test this hypothesis, inflammatory bone marrow-derived DCs (BMDCs) from C57Bl/6 mice were generated in the presence of vehicle or TCDD. TCDD decreased CD11c expression but increased MHC class II, CD86 and CD25 expression on the BMDCs. The effects of TCDD were strictly AhR-dependent but not exclusively DRE-mediated. Similar effects were observed with two natural AhR ligands, 6-formylindolo[3,2 b]carbazole (FICZ) and 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid (ITE). TCDD increased LPS- and CpG-induced IL-6 and TNF-alpha production by BMDCs but decreased their NO production. TCDD decreased CpG-induced IL-12p70 production by BMDCs but did not affect their secretion of IL-10. TCDD downregulated LPS- and CpG-induced NF-kB p65 levels and induced a trend towards upregulation of RelB levels in the BMDCs. AhR activation by TCDD modulated BMDC uptake of both soluble and particulate antigens. Induction of indoleamine-2,3-dioxygenase (IDO) and TGF beta3 has been implicated in the generation of regulatory T cells following AhR activation. TCDD increased IDO1, IDO2 and TGF-beta3 mRNA levels in BMDCs as compared to vehicle. Despite the induction of regulatory mediators, TCDD-treated BMDCs failed to suppress antigen-specific T cell activation. Thus, AhR activation can directly alter the differentiation and innate functions of inflammatory DCs without affecting their ability to successfully interact with T cells. PMID- 20350562 TI - Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet. AB - Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstalpha1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities. PMID- 20350564 TI - Snaclecs (snake C-type lectins) that inhibit or activate platelets by binding to receptors. AB - More than 300 known species of venomous snakes are classified into five families, Hydrophidae, Elapidae, Viperidae, Crotalidae and Colubidae. Venom proteins have also been demonstrated recently in other snakes and some lizards (Fry et al., 2006). Venom components that affect hemostasis are most generally found in Viperidae, and Crotalidae snakes but the others often contain some as well. This review concentrates on structural and functional properties of venom components of the C-type lectin related class (now named snaclecs) that inhibit or activate platelets by binding to receptors. PMID- 20350565 TI - Encoding natural scenes with neural circuits with random thresholds. AB - We present a general framework for the reconstruction of natural video scenes encoded with a population of spiking neural circuits with random thresholds. The natural scenes are modeled as space-time functions that belong to a space of trigonometric polynomials. The visual encoding system consists of a bank of filters, modeling the visual receptive fields, in cascade with a population of neural circuits, modeling encoding in the early visual system. The neuron models considered include integrate-and-fire neurons and ON-OFF neuron pairs with threshold-and-fire spiking mechanisms. All thresholds are assumed to be random. We demonstrate that neural spiking is akin to taking noisy measurements on the stimulus both for time-varying and space-time-varying stimuli. We formulate the reconstruction problem as the minimization of a suitable cost functional in a finite-dimensional vector space and provide an explicit algorithm for stimulus recovery. We also present a general solution using the theory of smoothing splines in Reproducing Kernel Hilbert Spaces. We provide examples of both synthetic video as well as for natural scenes and demonstrate that the quality of the reconstruction degrades gracefully as the threshold variability of the neurons increases. PMID- 20350563 TI - Identification of small-molecule inhibitors of ricin and shiga toxin using a cell based high-throughput screen. AB - The Category B agents, ricin and shiga toxin (Stx), are RNA N-glycosidases that target a highly conserved adenine residue within the sarcin-ricin loop of eukaryotic 28S ribosomal RNA. In an effort to identify small-molecule inhibitors of these toxins that could serve as lead compounds for potential therapeutics, we have developed a simple Vero cell-based high-throughput cytotoxicity assay and have used it to screen approximately 81,300 compounds in 17 commercially available chemical libraries. This initial screen identified approximately 300 compounds with weak (>or=30 to <50%), moderate (>or=50 to <80%), or strong (>or=80%) ricin inhibitory activity. Secondary analysis of 244 of these original "hits" was performed, and 20 compounds that were capable of reducing ricin cytotoxicity by >50% were chosen for further study. Four compounds demonstrated significant dose-dependent ricin inhibitory activity in the Vero cell-based assay, with 50% effective inhibitory concentration (EC(50)) values ranging from 25 to 60microM. The same 20 compounds were tested in parallel for the ability to inhibit ricin's and Stx1's enzymatic activities in an in vitro translation reaction. Three of the 20 compounds, including the most effective compound in the cell-based assay, had discernible anti-toxin activity. One compound in particular, 4-fluorophenyl methyl 2-(furan-2-yl)quinoline-4-carboxylate ("compound 8"), had 50% inhibitory concentration (IC(50)) of 30microM, a value indicating >10-fold higher potency than is the case for previously described ricin-Stx1 inhibitors. Computer modeling predicted that compound 8 is capable of docking within the ricin active site. In conclusion, we have used a simple high throughput cell-based method to identify several new small-molecule inhibitors of ricin and Stx. PMID- 20350566 TI - Lack of association between endothelial nitric oxide synthase gene G894T polymorphism hypertension in the Tunisian population. PMID- 20350567 TI - Measuring timbre discrimination with cross-faded synthetic tones. AB - The identification and discrimination of timbre are essential features of music perception. As timbre differences appear as multidimensional cues, the spectral shape, the spectral fluctuation, and the rise time are the most dominating parameters of timbre in normal-hearing listeners. We developed a psychoacoustical test to determine the timbre discrimination abilities using only the spectral difference as a cue. Therefore, a synthetically generated tone continuum was used in an adaptive alternative forced choice paradigm. The spectral difference was modified by cross-fading the tones adaptively, depending on the listeners' response which allows very precise determinations of the just noticeable difference (JND). We measured the JND for the spectral difference with 18 normal hearing listeners. The results confirm the applicability of the test to measure timbre discrimination with the spectral difference as solely cue. Further, the portability of the test to further dimensions of timbre is discussed. PMID- 20350569 TI - Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease. AB - Deficiency in 1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) has been suggested as an important environmental factor for immuno-mediated disorders including inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, both characterized by chronic intestinal inflammation. Administration of vitamin D receptor (VDR) agonists can ameliorate spontaneous and induced animal models of colitis, but hypercalcemia is a dose-limiting adverse event. Previous work in our laboratory has identified 1alpha,25(OH)(2)-16-ene-20-cyclopropyl vitamin D(3) (BXL-62) as a potent anti-inflammatory VDR agonist with a low calcemic activity. In the present study, we confirm the marked anti-inflammatory properties of BXL-62 and show its capacity to induce VDR primary response genes, like CYP24A1 and CAMP, at lower concentrations than 1,25D(3), in PBMCs from IBD patients. Its higher anti-inflammatory potency compared to 1,25D(3) was demonstrated by the significantly more potent inhibition in PBMCs and in lymphocyte-enriched lamina propria mononuclear cells of the pro-inflammatory cytokines TNF-alpha, IL-12/23p40, IL-6 and IFN-gamma, both at mRNA and protein level. The therapeutic efficacy of intra-rectal administration of BXL-62 in experimental IBD is shown by its beneficial effects, significantly higher than 1,25D(3), to induce recovery of clinical symptoms of colitis at normocalcemic doses in mice undergoing dextran sodium sulfate-induced colitis. These results confirm the therapeutic efficacy of VDR agonists in experimental colitis, and suggest BXL-62 as a promising compound for IBD treatment. PMID- 20350568 TI - A novel behavioral paradigm for assessing the concept of nests in mice. AB - Abstract concepts in the brain enable humans to efficiently and correctly recognize and categorize a seemingly infinite number of objects and daily events. Such abstract generalization abilities are traditionally considered to be unique to humans and perhaps non-human primates. However, emerging neurophysiological recordings indicate the existence of neural correlates for the abstract concept of nests in the mouse brain. To facilitate the molecular and genetic analyses of concepts in the mouse model, we have developed a nest generalization test based on the natural behavior of mice. We show that inducible and forebrain-specific NMDA receptor knockout results in pronounced impairment in this test. Interestingly, this generalization deficit could be gradually compensated for over time by repeated experiences even in the face of a continued deficit in object recognition memory. In contrast, the forebrain-specific presenilin-1 knockout mice, which have subtle phenotypes, were normal in performing this test. Therefore, our study not only establishes a quantitative method for assessing the nest concept in mice, but also demonstrates its great potential in combining powerful mouse genetics for dissecting the molecular basis of concept formation in the brain. PMID- 20350570 TI - Rescue of the mature B cell compartment in BAFF-deficient mice by treatment with recombinant Fc-BAFF. AB - BAFF deficiency in mice impairs B cell development beyond the transitional stage 1 in the spleen and thus severely reduces the size of follicular and marginal zone B cell compartments. Moreover, humoral immune responses in these mice are dramatically impaired. We now addressed the question whether the decrease in mature B cell numbers and the reduced humoral immune responses in BAFF-deficient mice could be overcome by the injection of recombinant BAFF. We therefore engineered a recombinant protein containing the human IgG1 Fc moiety fused to receptor-binding domain of human BAFF (Fc-BAFF). At 1 week after the second injection of this fusion protein a complete rescue of the marginal zone B cell compartment and a 50% rescue of the follicular B cell compartment was observed. Moreover these mice mounted a T cell-dependent humoral immune response indistinguishable from wild-type mice. By day 14 upon arrest of Fc-BAFF treatment mature B cell numbers in the blood dropped by 50%, indicating that the life span of mature B cells in the absence of BAFF is 14 days or less. Collectively these findings demonstrate that injection of Fc-BAFF in BAFF-deficient mice results in a temporary rescue of a functional mature B cell compartment. PMID- 20350572 TI - Perspective: time scales in scientific research with an emphasis on microbial cellular and molecular research. AB - Scientists use time to describe and research the universe in which humans live. Geologists and evolutionary biologists often use time scales in the millions to billions of years while biochemists and molecular biologists use time scales in the milliseconds or less. The atom smashers use time scales that are almost the speed of light. However, in some areas of research such as molecular-based activities in cells, it is very challenging to obtain data sets in molecular time scales. This has been a challenge to obtaining accurate and precise measurements at the cell and molecular levels of organization in living organisms. Measurements of specific cellular and molecular activities are often made over time scales longer than the actual molecular events. The data sets obtained become estimates over seconds, minutes and hours and not measurements over milli- and nanoseconds. The question can then be posed - how representative and accurate are our data sets when the time scales are not synchronized with the actual living events? In this article, the role of time scales in scientific research and our understanding of living microorganisms are examined with an emphasis on cell and molecular time scales. PMID- 20350573 TI - Inter-hemispheric electroencephalography coherence analysis: assessing brain activity during monotonous driving. AB - The current study investigated the effect of monotonous driving on inter hemispheric electroencephalography (EEG) coherence. Twenty-four non-professional drivers were recruited to perform a fatigue instigating monotonous driving task while 30 channels of EEG were simultaneously recorded. The EEG recordings were then divided into 5 equal sections over the entire driving period for analysis. Inter-hemispheric coherence was computed from 5 homologous EEG electrode pairs (FP1-FP2, C3-C4, T7-T8, P7-P8, and O1-O2) for delta, theta, alpha and beta frequency bands. Results showed that frontal and occipital inter-hemispheric coherence values were significantly higher than central, parietal, and temporal sites for all four frequency bands (p<0.0001). In the alpha frequency band, significant difference was found between earlier and later driving sections (p=0.02). The coherence values in all EEG frequency bands were slightly increased at the end of the driving session, except for FP1-FP2 electrode pair, which showed no significant change in coherence in the beta frequency band at the end of the driving session. PMID- 20350574 TI - Formation of autophagosomes and redistribution of LC3 upon in vitro infection with infectious salmon anemia virus. AB - Autophagy plays an important role in both cellular homeostasis and cellular stress responses, and is also implicated in viral immunity. Here we show that infectious salmon anemia virus (ISAV) induce autophagy (double membrane autophagosomes observed by EM), in cells from Atlantic salmon. In addition, cells transfected with the standard autophagy marker, microtubule-associated protein light chain kinase 3 (LC3) fused to green fluorescent protein (LC3-GFP), displayed the redistribution of fluorescence into the typical punctate pattern seen in cells undergoing autophagy (a marker for autophagosome formation). This redistribution is caused by transformation of the LC3 protein into a membrane bound form due to lipidation of the C-terminal glycine. RT-QPCR analysis of key autophagy protein transcripts (ATG 3, 5, 6, 7, 8, 10, 12) mRNA revealed no major changes in expression of autophagy genes in the first phase of ISAV infection. Treatment of cells with an inhibitor of autophagosome formation, 3-methyladenine, both reduced LC3-GFP puncta formation and viral production, suggesting a role for autophagosomes in ISAV replication. This is the first report of virus-induced autophagy in cells from a fish species. PMID- 20350571 TI - Characterisation of the bifunctional dihydrofolate synthase-folylpolyglutamate synthase from Plasmodium falciparum; a potential novel target for antimalarial antifolate inhibition. AB - Unusually for a eukaryote, the malaria parasite Plasmodium falciparum expresses dihydrofolate synthase (DHFS) and folylpolyglutamate synthase (FPGS) as a single bifunctional protein. The two activities contribute to the essential pathway of folate biosynthesis and modification. The DHFS activity of recombinant PfDHFS FPGS exhibited non-standard kinetics at high co-substrate (glutamate and ATP) concentrations, being partially inhibited by increasing concentrations of its principal substrate, dihydropteroate (DHP). Binding of DHP to the catalytic and inhibitory sites exhibited dissociation constants of 0.50microM and 1.25microM, respectively. DHFS activity measured under lower co-substrate concentrations, where data fitted the Michaelis-Menten equation, yielded apparent K(m) values of 0.88microM for DHP, 22.8microM for ATP and 5.97microM for glutamate. Of the substrates tested in FPGS assays, only tetrahydrofolate (THF) was efficiently converted to polyglutamylated forms, exhibiting standard kinetics with an apparent K(m) of 0.96microM; dihydrofolate, folate and the folate analogue methotrexate (MTX) were negligibly processed, emphasising the importance of the oxidation state of the pterin moiety. Moreover, MTX inhibited neither DHFS nor FPGS, even at high concentrations. Conversely, two phosphinate analogues of 7,8 dihydrofolate that mimic tetrahedral intermediates formed during DHFS- and FPGS catalysed glutamylation were powerfully inhibitory. The K(i) value of an aryl phosphinate analogue against DHFS was 0.14microM and for an alkyl phosphinate against FPGS 0.091microM, with each inhibitor showing a high degree of specificity. This, combined with the absence of DHFS activity in humans, suggests PfDHFS-FPGS might represent a potential new drug target in the previously validated folate pathway of P. falciparum. PMID- 20350575 TI - Age and meloxicam attenuate the ischemia/reperfusion-induced down-regulation in the NMDA receptor genes. AB - This study describes the effect of global brain ischemia followed by 48 h reperfusion, when delayed neuronal death can be already observed. We quantified the mRNA levels of the N-methyl-D-aspartate receptor (NMDAR) subunits and those of the astroglia (glial fibrilar acidic protein, GFAP) and microglia (CD11b) markers using real time PCR on the cerebral cortex and hippocampus of 3- and 18 month-old Sprague-Dawley rats. Data show an ischemia/reperfusion-induced decrease in the mRNA levels of the NMDAR NR1, NR2A and NR2B subunits genes, which contrasts with the increase in the CD11b and GFAP mRNA levels. These effects are attenuated in all the genes studied in 18-month-old animals, suggesting that this mechanism of response is less efficient in aged animals. Western blot assays of NR1, NR2A and NR2B show parallels with the real time PCR data, indicating that the down-regulation of these genes is controlled at the transcriptional level. We suggest that a decrease in the efficiency in the control of the NMDAR transcription could account for the higher vulnerability in aged animals, but it cannot explain by itself differences in the vulnerability to ischemia in different areas of the brain. In the assays of ischemia/reperfusion followed by a treatment with the anti-inflammatory agent meloxicam, we observed that ischemic insult was unable to elicit changes in the NMDAR transcription, thus suggesting that inflammation plays a crucial role in the transcriptional control of these genes. PMID- 20350576 TI - Genome-wide microarray analysis of brain gene expression in mice on a short-term high iron diet. AB - The effects of systemic iron overload on the brain are unclear. Microarray analysis of brain gene expression in mice following short-term iron supplementation revealed altered expression of 287 genes, although most changes were small. Transcripts for the iron storage protein ferritin light chain increased 20% (p=0.002) and transcripts for iron regulatory protein 1, which negatively regulates ferritin translation, decreased 28% (p=0.048). There were expression changes for genes involved in important brain functions such as neurotransmission and nitric oxide signaling, which is dependent on iron. Few changes related to reactive oxygen species, inflammation or apoptosis, however expression changes were observed for genes causatively linked to neurological disorders, including Charcot-Marie-Tooth disease, neuronal ceroid lipofuscinosis and mucolipidosis. The latter involve intralysosomal lipofuscin build-up that may reflect lysosomal iron accumulation. The findings suggest that high iron intake may cause subtle brain effects of clinical relevance in some circumstances. PMID- 20350577 TI - Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. AB - Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of liver failure, characterized neuropathologically by astrocyte swelling, microglial activation and Alzheimer Type II astrocytosis. Molecular studies in HE brain reveal altered expression of genes coding for key astroglial proteins including early losses of expression of GFAP and the glutamate transporter EEAT-2 with concomitant increases of the astrocytic/microglial mitochondrial benzodiazepine receptor (MBR). Decreased expression of EAAT-2 results in decreased glutamate transport and impaired cycling of glutamate-glutamine between astrocytes and neurons, as well as increased extracellular glutamate, activation of the NMDA receptor-mediated cGMP-NO signal transduction pathway, and nitration of tyrosine residues on key astroglial proteins such as glutamine synthetase (GS) and the MBR. GS is uniquely responsible for the removal of excess ammonia in brain. Ammonia-induced activation of MBR in astrocytes and/or microglia results in stimulation of the synthesis of neurosteroids such as allopregnanolone with positive allosteric GABA-A receptor neuromodulatory properties. Allopregnanolone concentrations are increased up to 7-fold in HE brain. Attenuation of microglial activation by minocycline results in a delay in onset of HE and prevents brain edema in liver failure. Mild hypothermia is likewise beneficial in acute liver failure resulting in normalization of extracellular brain glutamate and prevention of oxidative/nitrosative stress in experimental animals with HE resulting from either ischemic or toxic liver injuries. PMID- 20350578 TI - Juvenile animal testing in drug development--is it useful? AB - In pharmaceutical drug development, there has been increased interest in the need to perform juvenile animal studies to support the safety of use of new medicines in the pediatric population. Although such studies are not new, the increased interest has been "formalized" in recent regulatory guidelines. As a result, companies are now performing many more studies in juvenile animals, even when there is a lack of robust knowledge of cross-species functional and kinetic differences among juveniles that means extrapolation of any toxicology study finding to an immature human may not be easy or even relevant, especially if performed in the wrong species at the wrong time. It will be shown by presentation of some basic considerations needed in order to perform such testing, that juvenile animal studies are indeed feasible. However, it will also be highlighted that (based on available knowledge) there are currently not enough clear-cut examples to answer the question of whether juvenile animal toxicology studies to support pediatric development (by affecting the performance or design of a pediatric clinical trial or identifying a potential different-from-adult safety risk in clinical use) are truly useful or necessary. PMID- 20350580 TI - A convenient and robust method for construction of combinatorial and random mutant libraries. AB - Here we describe a convenient and robust ligase-independent method for construction of combinatorial and random mutant libraries. The homologous genes flanked by plasmid-derived DNA sequences are fragmented, and the random fragments are reassembled in a self-priming polymerase reaction to obtain chimeric genes. The product is then mixed with linearized vector and two pairs of flanking primers, followed by assembly of the chimeric genes and linearized vector by PCR to introduce recombinant plasmids of a combinatorial library. Commonly, it is difficult to find proper restriction sites during the construction of recombinant plasmids after DNA shuffling with multiple homologous genes. However, this disadvantage can be overcome by using the ligase-independent method because the steps of DNA digestion and ligation can be avoided during library construction. Similarly, DNA sequences with random mutations introduced by error-prone PCR can be used to construct recombinant plasmids of a random mutant library with this method. Additionally, this method can meet the needs of large and comprehensive DNA library construction. PMID- 20350579 TI - Protective effects of silica hydride against carbon tetrachloride-induced hepatotoxicity in mice. AB - The protective effects of MegaHydrate silica hydride against liver damage were evaluated by its attenuation of carbon tetrachloride (CCl(4))-induced hepatotoxicity in mice. Male ICR mice were orally treated with silica hydride (104, 208 and 520 mg/kg) or silymarin (200 mg/kg) daily, with administration of CCl(4) (1 mL/kg, 20% CCl4 in olive oil) twice a week for eight weeks. The results showed that oral administration of silica hydride significantly reduced the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), and cholesterol and the level of malondialdehyde (MDA) in the liver that were induced by CCl(4) in mice. Moreover, the silica-hydride treatment was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px), as well as increase the GSH content, in the liver. Liver histopathology also showed that silica hydride reduced the incidence of liver lesions induced by CCl(4). The results suggest that silica hydride exhibits potent hepatoprotective effects on CCl(4)-induced liver damage in mice, likely due to both the increase of antioxidant-defense system activity and the inhibition of lipid peroxidation. PMID- 20350581 TI - Statistical evidence for ancestral correlation patterns. AB - Statistical correlations in DNA sequences are an important source of information for processes of genome evolution. As a special case of such correlations and building up on our previous work, here we study, how short-range correlations in Eukaryotic genomes change under elimination of various classes of repetitive DNA. Our main result is that a residual correlation pattern, common to most mammalian species, emerges under elimination of all repetitive DNA, suggesting features of an ancestral correlation signature. Furthermore, using this general framework, we find classes of repeats, which upon deletion move the correlation pattern towards this residual pattern (simple repeats and SINEs) or away from this residual pattern (LINEs). These findings suggest that the common correlation pattern visible in the mammalian species after repeat elimination can be associated with a common mammalian ancestor. PMID- 20350582 TI - The probable relation between Toxoplasma gondii and Parkinson's disease. AB - Parkinson's disease (PD), a chronic progressive neurodegenerative disorder, has a mainly unknown multifactorial etiology. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. Toxoplasmosis can be associated with various neuropsychiatric disorders. The most commonly affected central nervous system (CNS) region in toxoplasmosis is the cerebral hemisphere, followed by the basal ganglia, cerebellum and brain stem. Therefore, in this study, we aimed to investigate the possible association between Toxoplasma infection and PD by evaluating the serum anti-Toxoplasma gondii IgG antibodies. There were no difference between the socioeconomic status of the patients and control subjects and magnetic resonance images of the patients were normal. Serum anti-T. gondii IgG levels were measured using ELISA. There was no statistically significant differences among the patients and control subjects with respect to age (66.01+/-12.14 years, 62.42+/-5.93 years, p=0.089; respectively) and gender. The sero-positivity rate for anti-T. gondii IgG antibodies in PD patients and control groups were 42.3 and 22.5%, respectively, and they were statistically significant (p=0.006). These results suggest that Toxoplasma infection may be involved in the pathogenetic mechanisms of PD. If confirmed, this hypothesis would represent a valuable advancement in care of patients with Parkinson's disease. PMID- 20350583 TI - Increased plasma levels of brain-derived neurotrophic factor in patients with long-term bipolar disorder. AB - Recent data indicate that neurotrophins may play a role in the physiopathology of bipolar disorder (BD) and may be useful as biomarkers of the disease. The aim of this study was to evaluate the plasma concentrations of brain-derived neurotrophic factor (BDNF) in BD patients, and to correlate their levels with clinical parameters. BDNF was measured in plasma from 53 BD type I subjects (34 during mania and 19 during euthymia) and 38 healthy controls by enzyme-linked immuno-sorbent assay (ELISA). Patients were assessed by a structured clinical interview (Mini-plus), Young mania and Hamilton depression rating scales. Plasma BDNF levels were significantly increased in patients with mania (PG) in intron 8 of UBQLN 1 at the rs12344615 site (UBQ-8i) on chromosome 9q22 was associated with a higher risk of late-onset Alzheimer's disease (AD). Here, we aimed to investigate whether an association exists between the UBQ-8i polymorphism and AD in Taiwan Chinese. Initially, we included 100 late-onset AD patients and 100 gender- and age-matched non-demented (ND) control participants. The UBQ-8i polymorphism site was successfully determined in 91 AD and 96 ND individuals using the dye terminator nucleotide sequencing technique. Among the 187 participants, we did not detect any subject carrying the G allele. This finding is in agreement with the report listed in the NCBI SNP Reference Assembly, which states that <1% of Asians carry this SNP. The APOE varepsilon4 allele, an established AD genetic risk factor, was overrepresented in the AD cohort. We conclude from these results that the UBQ-8i polymorphism of the UBQLN1 gene is extremely rare in Taiwan Chinese and unlikely to play a significant role in the risk of AD in Taiwan Chinese. PMID- 20350586 TI - Effects of varying the load force range and frequency on force coordination in static manipulation. AB - A frequency associated deterioration of the hand grip (GF; normal component of force acting at the digits-object contact area) and load force (LF; the tangential component) coordination has been demonstrated in a variety of repetitive manipulation tasks. However, it remains unknown whether the effect originates from the task frequency per se, or from the rate of LF change (a prediction that could be derived from the minimum jerk hypothesis) which increases with both LF frequency and LF range. The aim of the study was to discern between the effects of LF frequency and LF range (which affects only the rate of LF) in static manipulation tasks. Subjects (N=15) exerted a sinusoidal LF pattern against an externally fixed instrumented handle at 5 different LF frequencies (0.67-3.33Hz) and ranges (6-30N). The results revealed weak and mainly non-significant effects of both LF range and frequency on GF scaling (GF/LF ratio). However, both GF-LF coupling (assessed by correlation coefficients) and GF modulation (change in GF relative to LF variation) demonstrated a prominent decrease associated with LF frequency, but not with LF range. The observed findings were interpreted by switching between hypothetical synergies of GF and LF producing muscles separately employed in the phases of the increasing and decreasing forces. From the practical aspect, however, the results suggest that the frequency, but not the LF range should be taken into account when designing rhythmic manipulation tasks, developing standard tests of hand function based on GF-LF coordination, or comparing the data from different studies. PMID- 20350587 TI - Medial temporal lobe dysfunction during encoding and retrieval of episodic memory in non-demented APOE epsilon4 carriers. AB - Presence of the apolipoprotein E (APOE) epsilon4 allele is linked to an increased risk to develop Alzheimer's dementia (AD). However, there are controversial data concerning the impact of the APOE genotype on cognitive functioning and brain activity in healthy subjects. We used event-related functional magnetic resonance imaging (fMRI) to investigate the effects of APOE genotype on spatial contextual memory encoding and retrieval success in healthy older adults. Eighteen subjects (eight APOE4 heterozygotes (epsilon4+) and 10 non-carriers (epsilon4-), mean age 60.0+/-5.0 years) were included in the present analysis. Behaviorally, epsilon4+ subjects performed significantly worse than epsilon4- subjects in item memory and spatial context retrieval. fMRI data revealed that epsilon4+ subjects, compared to epsilon4-subjects, predominantly showed an increase of neural activity specific to encoding of items and their spatial context in prefrontal, temporal and parietal regions. In contrast, epsilon4+ subjects showed activity decreases in the right amygdala during successful item recognition and in the prefrontal cortex bilaterally during spatial context retrieval when compared to epsilon4- subjects. While the activity increases during encoding may reflect compensatory activity in the attempt to maintain normal performance, the decreases during retrieval indicate incipient neural decline in epsilon4+ subjects. These data highlight that preclinical ApoE-related changes in neural activity are not unidirectional but dissociate depending on the memory phase, i.e., encoding or retrieval. PMID- 20350589 TI - Uncovering the molecular basis of positive affect using rough-and-tumble play in rats: a role for insulin-like growth factor I. AB - Positive emotional states have been shown to confer resilience to depression and anxiety in humans, but the molecular mechanisms underlying these effects have not yet been elucidated. In laboratory rats, positive emotional states can be measured by 50-kHz ultrasonic vocalizations (hedonic USVs), which are maximally elicited by juvenile rough-and-tumble play behavior. Using a focused microarray platform, insulin-like growth factor I (IGFI) extracellular signaling genes were found to be upregulated by hedonic rough-and-tumble play but not depressogenic social defeat. Administration of IGFI into the lateral ventricle increased rates of hedonic USVs in an IGFI receptor (IGFIR)-dependent manner. Lateral ventricle infusions of an siRNA specific to the IGFIR decreased rates of hedonic 50-kHz USVs. These results show that IGFI plays a functional role in the generation of positive affective states and that IGFI-dependent signaling is a potential therapeutic target for the treatment of depression and anxiety. PMID- 20350590 TI - Group cohesiveness during collective movements: travelling apart together. PMID- 20350588 TI - Selective potentiation of the metabotropic glutamate receptor subtype 2 blocks phencyclidine-induced hyperlocomotion and brain activation. AB - Previous preclinical and clinical studies have demonstrated the efficacy of group II metabotropic glutamate receptor (mGluR) agonists as potential antipsychotics. Recent studies utilizing mGluR2-, mGluR3-, and double knockout mice support that the antipsychotic effects of those compounds are mediated by mGluR2. Indeed, biphenyl indanone-A (BINA), an allosteric potentiator of mGluR2, is effective in experimental models of psychosis, blocking phencyclidine (PCP)-induced hyperlocomotion and prepulse inhibition deficits in mice. In this study, we administered the NMDA receptor antagonist PCP (5.6 mg/kg i.p.) to rats, an established animal model predictive of schizophrenia. Here, we show that BINA (32 mg/kg i.p.) attenuated PCP-induced locomotor activity in rats. Using behaviorally relevant doses of BINA and PCP, we performed pharmacological magnetic resonance imaging (phMRI) to assess the specific brain regions that underlie the psychotomimetic effects of PCP, and examined how BINA modulated the PCP-induced functional changes in vivo. In anesthetized rats, acute administration of PCP produced robust, sustained blood oxygenation level-dependent (BOLD) activation in specific cortical, limbic, thalamic, and striatal regions. Pretreatment with BINA suppressed the amplitude of the BOLD response to PCP in the prefrontal cortex, caudaute-putamen, nucleus accumbens, and mediodorsal thalamus. Our results show key brain structures underlying PCP-induced behaviors in a preclinical model of schizophrenia, and, importantly, its reversal by potentiation of mGluR2 by BINA, revealing specific brain regions functionally involved in its pharmacological action. Finally, our findings bolster the growing body of evidence that mGluR2 is a viable target for the treatment of schizophrenia. PMID- 20350591 TI - Follow me! I'm a leader if you do; I'm a failed initiator if you don't? PMID- 20350592 TI - Deciding group movements: where and when to go. AB - A group of animals can only move cohesively, if group members "somehow" reach a consensus about the timing (e.g., start) and the spatial direction/destination of the collective movement. Timing and spatial decisions usually differ with respect to the continuity of their cost/benefit distribution in such a way that, in principle, compromises are much more feasible in timing decision (e.g., median preferred time) than they are in spatial decisions. The consequence is that consensus costs connected to collective timing decisions are usually less skewed amongst group members than are consensus costs connected to spatial decisions. This, in turn, influences the evolution of decision sharing: sharing in timing decisions is most likely to evolve when conflicts are high relative to group cohesion benefits, while sharing in spatial decisions is most likely to evolve in the opposite situation. We discuss the implications of these differences for the study of collective movement decisions. PMID- 20350593 TI - Profiling of cold-stress-responsive miRNAs in rice by microarrays. AB - MicroRNAs (miRNAs) are small single-stranded RNAs with a length of about 21 nt; these non-coding RNAs regulate developmental and stress responses in plants by cleaving mRNAs. Cold stress is one of the most severe abiotic stresses and adversely affects rice yields by restraining sowing time, causing tissue damage, and stunting growth. Although many miRNAs have been identified in rice, little is known about the role of miRNAs in the response to cold stress. In this study, we identified 18 cold-responsive rice miRNAs using microarrays. Most were down regulated. Members of the miR-167 and miR-319 families showed similar profiles. Intriguingly, members of miR-171 family showed diverse expression patterns. Three miRNAs derived from transposable element sequence were clustered within an intron and proved to be co-transcribed with the host gene only under cold stress. The existence of hormone-responsive elements in the upstream regions of the cold responsive miRNAs indicates the importance of hormones in this defense system mediated by miRNAs. Two miRNA target pairs validated by 5' RACE showed opposite expression profiles under cold stress. Finally, the predicted stress-related targets of these miRNAs provided further evidence supporting our results. These findings confirm the role of miRNAs as ubiquitous regulators in rice. PMID- 20350594 TI - How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). AB - Recent evidence suggests that calorie restriction and specifically reduced glucose metabolism induces mitochondrial metabolism to extend life span in various model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and possibly mice. In conflict with Harman's free radical theory of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately cause a long-term reduction of oxidative stress. This type of retrograde response has been named mitochondrial hormesis or mitohormesis, and may in addition be applicable to the health-promoting effects of physical exercise in humans and, hypothetically, impaired insulin/IGF-1-signaling in model organisms. Consistently, abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. In summary, the findings discussed in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond. PMID- 20350595 TI - Xenobiotic metabolism gene expression in the EpiDermin vitro 3D human epidermis model compared to human skin. AB - There is an urgent need to validate in vitro human skin models for use in safety testing. An important component of validation is characterizing the metabolizing capacity of these models. We report comparison of the expression of 139 genes encoding xenobiotic metabolizing enzymes in the EpiDerm model and human skin. In microarray analysis, the expression of 87% of the genes was consistent between the EpiDerm model and human skin indicating the presence of similar metabolic pathways suggesting commonality in function. Analysis of EpiDerm models constructed from four donors showed highly comparable expression of xenobiotic metabolizing genes demonstrating reproducibility of the model. Overall, the expression of Phase II enzymes appeared to be more pronounced in human skin and the EpiDerm model than that of Phase I enzymes, consistent with the role of skin in detoxification of xenobiotics. Though the basal expression of CYPs in particular was low in EpiDerm, significant induction of CYP1A1/1B1 activity was observed following treatment with 3-methylcholanthrene. These results indicate that the xenobiotic metabolizing capacity of the EpiDerm model appears to be representative of human skin. Models such as EpiDerm provide a valuable in vitro approach for evaluation of metabolism and toxicity of cutaneous exposures to xenobiotics. PMID- 20350596 TI - A novel profluorescent nitroxide as a sensitive probe for the cellular redox environment. AB - Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders. Sensitive quantification of these changes has been developed using a novel fluorescent probe containing a redox sensitive nitroxide moiety. As well as being able to selectively detect the superoxide radical in vitro, this method can measure overall changes to the cellular redox environment using flow cytometry on the basis of nitroxide reduction. The reversible nature of the probe's detection mechanism offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. PMID- 20350598 TI - Adhesion testing of transdermal matrix patches with a probe tack test--in vitro and in vivo evaluation. AB - It was the aim of the study to evaluate the suitability of the probe tack test as a method of predicting the long-term adhesion properties of transdermal patches to human skin. Twelve different types of polyacrylate pressure sensitive adhesives have been characterized using the probe tack test. For the analysis of the obtained data a novel procedure was developed that is based on two parameters: the deformation compliance kappa and the critical return speed v(c). In addition to the in vitro characterization, the in vivo adhesive properties were investigated in a double-blinded and randomized wear study by eight volunteers for a period of 7days of wear. The adherent area and the size of the dark ring were defined in a percentage of the patch area by analysing digital photographs. The in vitro data correlate mostly with the in vivo performance of the tested adhesives after 7days. Accordingly, the probe tack test could be a helpful tool during the development of transdermal patches. PMID- 20350597 TI - Repeated exposures to low-level chlorpyrifos results in impairments in sustained attention and increased impulsivity in rats. AB - Organophosphates such as chlorpyrifos (CPF) are among the most commonly used pesticides in the world. Therefore, it is not surprising that measurable levels of organophosphates (including CPF) are found in over 50% of fresh fruits, vegetables and grains that we consume and that approximately 80% of adults in the US have detectable levels of CPF metabolites in their urine. It is well known that acute exposure to organophosphates can cause cognitive deficits; however, the effects of daily or intermittent contact with low levels of organophosphates (often reflective of environmental exposures) are not well understood. The objective of this study was to determine if repeated low-level exposures to CPF impaired the performance of the 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT, then treated with vehicle or CPF 18.0 mg/kg daily for 14 consecutive days or every other day for 30 days. Behavioral testing occurred daily during the CPF-exposure period and throughout a 30 day washout period to assess recovery. All CPF-treated animals exhibited deficits in percent correct, an increase in omissions and premature responses without signs of impaired motivation or overt toxicity. Deficits in 5C-SRTT accuracy were apparent well into the 30 day washout period despite significant recovery of cholinesterase activity. These results indicate that repeated exposures to relatively low levels of chlorpyrifos lead to protracted impairments of sustained attention and an increase in impulsive behaviors in rats. PMID- 20350599 TI - Persephin signaling through GFRalpha1: the potential for the treatment of Parkinson's disease. AB - Neurotrophic factors promote survival, proliferation and differentiation of neurons inducing intracellular signaling via specific receptors. The conventional biochemical methods often fail to reveal full repertoire of neurotrophic factor receptor interactions because of their limited sensitivity. We evaluated several approaches to study signaling of Glial cell line-Derived Neurotrophic Factor (GDNF) family ligands and found that reporter-gene systems possess exceptionally high sensitivity and a heuristic power to identify novel biologically relevant growth factor-receptor interactions. We identified persephin, a GDNF family member, as a novel ligand for GFRalpha1/RET receptor complex. We confirmed this finding by several independent methods, including neurite outgrowth assay from the explants of sympathetic ganglia expressing Gfralpha1 and Ret mRNA but not persephin's conventional receptor GFRalpha4. As the activation of GFRalpha1/RET was shown to rescue dopaminergic neurons, our results suggest the potential of persephin for the treatment of Parkinson's disease. PMID- 20350600 TI - Zernike phase contrast cryo-electron tomography. AB - Cryo-tomography in the electron microscope is unique in its ability to provide high-resolution, three-dimensional structural information about cells, organelles and macromolecules in a nearly native, frozen-hydrated state. However, the phase contrast imaging method used in conventional cryo-electron tomography fails to faithfully represent the full range of structural features in such specimens. Only certain features are recorded with adequate contrast, and overall contrast is low. The recently developed Zernike phase contrast method has the potential to solve this problem, and here we apply it for the first time to cryo-electron tomography. The new method has uniform transfer characteristics for a wide range of spatial frequencies, leading to improved overall signal-to-noise ratio and raising the prospects of higher resolution and quantitative representation of specimen densities in the reconstructed tomograms. PMID- 20350601 TI - Crystal analysis and high-resolution imaging of microfibrillar alpha-chitin from Phaeocystis. AB - The ultrastructure of alpha-chitin microfibril produced by marine alga Phaeocystis was investigated by FT-IR spectroscopy, X-ray diffraction and electron microscopy. The average size of the microfibril was 17.1+/-1.8 MUm in length and 39.8+/-8.8 nm in width. The FT-IR spectrum shows typical alpha-chitin pattern, and each band was sharper than crustacean chitin's, indicating higher crystallinity of the Phaeocystis chitin. The X-ray diffraction gave crystallite size more than twice of crustacean tendon's. The fiber diffraction pattern is consistent with previous studies with two-chains orthorhombic unit cell (Minke and Blackwell, 1978; Sikorski et al., 2009), and refined unit cell dimensions are a=4.742 A, b=18.871 A, c=10.338A. High-resolution electron microscopy of ultrathin sections gave the cross-sectional shape of microfibril as hexagon. The lattice images of (020) plane (d=0.94 nm) were frequently observed extending the entire cross-section of microfibril, indicating its single crystalline nature. These results allowed construction of a molecular packing model for alpha-chitin crystal. PMID- 20350602 TI - Solution structures of 2*6-meric and 4*6-meric hemocyanins of crustaceans Carcinus aestuarii, Squilla mantis and Upogebia pusilla. AB - Arthropod hemocyanins (Hcs) are a family of large, high molecular mass, extracellular oxygen transport proteins. They form oligomeric quaternary structures based on different arrangements of a basic 6*75 kDa hexameric unit. Their complex quaternary structures present binding sites for allosteric effectors and regulate the oxygen binding process in a cooperative manner. In order to describe the functional regulation of arthropod Hcs, a detailed description of their quaternary structure is necessary. We have utilized small angle X-ray scattering to characterize the structure of three arthropod Hcs in unperturbed conditions. Two different levels of complexity are evaluated: for the 2*6-meric case, we analyzed the Hcs of the portunid crab Carcinus aestuarii and stomatopod Squilla mantis, while in the case of 4*6-meric structures, we studied the Hc of the thalassinid shrimp Upogebia pusilla. While C. aestuarii Hc presented a structure comparable to other 2*6-meric crustacean Hcs, S. mantis Hc shows a peculiar and quite unique arrangement of its building blocks, resembling a substructure of giant Hcs found among cheliceratans. For U. pusilla, the arrangement of its subunits is described as tetrahedral, in contrast to the more common square planar 4*6-meric structure found in other arthropod Hcs. PMID- 20350603 TI - Frequency-dependent neural activity, CBF, and BOLD fMRI to somatosensory stimuli in isoflurane-anesthetized rats. AB - Inhalation anesthetics (e.g. isoflurane) are preferable for longitudinal fMRI experiments in the same animals. We previously implemented isoflurane anesthesia for rodent forepaw stimulation studies, and optimized the stimulus parameters with short stimuli (1-3-s long stimulation with ten electric pulses). These parameters, however, may not be applicable for long periods of stimulation because repetitive stimuli induce neural adaptation. Here we evaluated frequency dependent responses (pulse width of 1.0 ms and current of 1.5 mA) for 30-s long stimulation under 1.3-1.5% isoflurane anesthesia. The cerebral blood flow (CBF) response (using laser Doppler flowmetry: CBF(LDF)) and field potential (FP) changes were simultaneously measured for nine stimulus frequencies (1-24 Hz). CBF (using arterial spin labeling: CBF(ASL)) and blood oxygenation level dependent (BOLD) fMRI responses were measured at 9.4 T for four stimulus frequencies (1.5 12 Hz). Higher stimulus frequencies (12-24 Hz) produced a larger FP per unit time initially, but decreased more rapidly later due to neural adaptation effects. On the other hand, lower stimulus frequencies (1-3 Hz) induced smaller, but sustained FP activities over the entire stimulus period. Similar frequency dependencies were observed in CBF(LDF), CBF(ASL) and BOLD responses. A linear relationship between FP and CBF(LDF) was observed for all stimulus frequencies. Stimulation frequency for the maximal cumulative neural and hemodynamic changes is dependent on stimulus duration; 8-12 Hz for short stimulus durations (<10s) and 6-8 Hz for 30-s stimulation. Our findings suggest that neural adaptation should be considered in determining the somatosensory stimulation frequency and duration under isoflurane anesthesia. PMID- 20350604 TI - Quantifying axon diameter and intra-cellular volume fraction in excised mouse spinal cord with q-space imaging. AB - Q-space magnetic resonance imaging (QSI) can quantify white matter (WM) axonal architecture at the cellular level non-destructively, unlike histology, but currently has several limitations. First, current methodology does not differentiate between diffusing molecules occupying extra- or intra-cellular spaces (ECS and ICS, respectively). Second, accurate assessment of axonal architecture requires high-gradient amplitudes not clinically available. Third, the only direct QSI marker of axonal architecture has been mean axon diameter (MAD), even though other direct markers would be valuable as well. The objective was to investigate three QSI-based methods that address the above limitations. Method 1 employs a two-compartment model to account for signal from ECS and ICS. Method 2 uses data only from low q-values thereby obviating the need for high gradient amplitudes. Method 3 empirically estimates ICS volume fraction and provides an additional metric of axonal architecture. We implemented each method on data from excised healthy adult mouse spinal cords collected previously using a home-built 50T/m z-gradient yielding sub-micron displacement resolution. Through comparison with histology, each method was evaluated for accuracy in assessing axonal architecture. MAD measured with Methods 1 and 2 showed good correlation with histology (R(2)=0.99 (p<0.0001), and 0.77 (p<0.01), respectively) and Bland-Altman analysis indicates that measurements from the two methods are not significantly different from histology. The third method measured ICS volume fractions (0.64+/-0.07) that were highly correlated (R(2)=0.92, p<0.05) with measurements from histology (0.68+/-0.07). These methods may provide insight into axonal architecture in normal and abnormal WM tissue but additional validation with more samples will be needed. PMID- 20350605 TI - Vascular contributions to pattern analysis: comparing gradient and spin echo fMRI at 3T. AB - Multivariate pattern analysis is often assumed to rely on signals that directly reflect differences in the distribution of particular neural populations. The source of the signal used in these analyses remains unclear however, and an alternative model suggests that signal from larger draining veins may play a significant role. The current study was designed to investigate the vascular contribution to pattern analyses at 3T by comparing the results obtained from gradient and spin echo data. Classification analyses were carried out comparing line orientations in V1, tone frequencies in A1, and responses from different fingers in M1. In all cases, classification accuracy in the spin echo data was not significantly different from chance. In contrast, classification accuracies in the gradient echo data were significantly above chance, and significantly higher than the accuracies observed for the spin echo data. These results suggest that at the field strength and spatial resolution used for the majority of fMRI studies, a considerable proportion of the signal used by pattern analysis originates in the vasculature. PMID- 20350607 TI - Transcranial direct current stimulation (tDCS) in a realistic head model. AB - Distributions of current produced by transcranial direct current stimulation (tDCS) in humans were predicted by a finite-element model representing several individual and collective refinements over prior efforts. A model of the entire human head and brain was made using a finely meshed (1.1x1.1x1.4mm(3) voxel) tissue dataset derived from the MRI data set of a normal human brain. The conductivities of ten tissues were simulated (bone, scalp, blood, CSF, muscle, white matter, gray matter, sclera, fat, and cartilage). We then modeled the effect of placing a "stimulating" electrode with a saline-like conductivity over F3, and a similar "reference" electrode over a right supraorbital (RS) location, as well as the complements of these locations, to compare expectations derived from the simulation with experimental data also using these locations in terms of the presence or absence of subjective and objective effects. The sensitivity of the results to changes in conductivity values were examined by varying white matter conductivity over a factor of ten. Our simulations established that high current densities were found directly under the stimulating and reference electrodes, but values of the same order of magnitude occurred in other structures, and many areas of the brain that might be behaviorally active were also subjected to what may be substantial amounts of current. The modeling also suggests that more targeted stimulations might be achieved by different electrode topologies. PMID- 20350608 TI - Subcortical functional connectivity and verbal episodic memory in healthy elderly -a resting state fMRI study. AB - Imaging research into age-related changes in episodic memory has mainly focused on changes in cortical areas in the medial temporal lobe and the hippocampus. However, several lines of evidence indicate that subcortical structures such as the basal ganglia and the thalamus are also involved in episodic memory function. Recent studies have revealed age-related changes in functional connectivity between different brain areas, as measured by resting state fMRI. It remains to be shown whether functional connectivity measures in the basal ganglia and the thalamus can be associated with age-related changes in memory function. Here, we investigate this question by applying high model order spatial independent component analysis to resting state fMRI data in a cohort of 100 healthy elderly and relate connectivity features to verbal episodic memory function as assessed by the California Verbal Learning Test (CVLT). We identified five components that were located within different parts of the thalamus and the basal ganglia. Two of these components demonstrated negative correlations between their functional connectivity level and CVLT performance. We also found negative correlations between connectional strength within subcortical structures and CVLT performance. These results indicate a previously undocumented role for the putamen and the thalamus in verbal episodic memory function in aging. PMID- 20350606 TI - The effect of different anesthetics on neurovascular coupling. AB - To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used. PMID- 20350609 TI - New selective medium for selection of bifidobacteria from human feces. AB - This work reports an alternative selective medium for reliable and efficient isolation of human fecal bifidobacteria. It uses a base commercially available, does not need pH adjustment and can be autoclaved with its additives. It provides a useful alternative for fecal bifidobacteria isolation. PMID- 20350610 TI - HLA-DPB1 mismatching results in the generation of a full repertoire of HLA-DPB1 specific CD4+ T cell responses showing immunogenicity of all HLA-DPB1 alleles. AB - Clinical studies have indicated that HLA-DPB1 functions as a classical transplantation antigen in allogeneic stem cell transplantation. Mismatching for HLA-DPB1 was associated with an increased risk of graft-versus-host disease (GVHD), but also a decreased risk of disease relapse. However, specific HLA-DPB1 mismatches were associated with poor clinical outcome. It was suggested that this unfavorable effect was caused by a difference in immunogenicity between HLA-DPB1 alleles. To analyze whether immunogenicity of HLA-DPB1 mismatches could be predicted based on the presence or absence of specific amino acid sequences we developed a model to generate allo-HLA-DPB1 responses in vitro. We tested in total 48 different stimulator/responder combinations by stimulating CD4(+) T cells from 5 HLA-DPB1 homozygous individuals with the same antigen-presenting cells transduced with different allo-HLA-DPB1 molecules. HLA-DPB1 molecules used for stimulation comprised 76% to 99% of HLA-DPB1 molecules present in different ethnic populations. We show that all HLA-DPB1 mismatches as defined by allele typing resulted in high-frequency immune responses. Furthermore, we show that crossrecognition of different HLA-DPB1 molecules is a broadly observed phenomenon. We confirm previously described patterns in crossrecognition, and demonstrate that a high degree in similarity between HLA-DPB1 molecules is predictive for crossrecognition, but not for immunogenicity. PMID- 20350611 TI - Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. AB - Despite advances in graft-versus-host-disease (GVHD) treatment, it is estimated that overall survival (OS) at 2 years for hematopoietic cell transplantation (HCT) recipients who experience steroid-resistant GVHD is 10%. Among recent therapeutic approaches for GVHD treatment, mesenchymal stromal cells (MSCs) hold a key position. We describe a multicenter experience of 11 pediatric patients diagnosed with acute or chronic GVHD (aGVHD, cGVHD) treated for compassionate use with GMP-grade unrelated HLA-disparate donors' bone marrow-derived MSCs, expanded in platelet-lysate (PL)-containing medium. Eleven patients (aged 4-15 years) received intravenous (i.v.) MSCs for aGVHD or cGVHD, which was resistant to multiple lines of immunosuppression. The median dose was 1.2 x 10(6)/kg (range: 0.7-3.7 x 10(6)/kg). No acute side effects were observed, and no late side effects were reported at a median follow-up of 8 months (range: 4-18 months). Overall response was obtained in 71.4% of patients, with complete response in 23.8% of cases. None of our patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD. This study underlines the safety of PL-expanded MSC use in children. MSC efficacy seems to be greater in aGVHD than in cGVHD, even after failure of multiple lines of immunosuppression. PMID- 20350612 TI - The role of membrane proteins in mammalian autophagy. AB - Autophagy is an evolutionarily conserved degradative process that is initiated by autophagosomes, double-membrane structures that sequester cytoplasmic material and fuse with endosomes and lysosomes to become autolysosomes. Recent progress in the identification of proteins required for autophagy has led to a substantial understanding of the process involved in making an autophagosome. Mammalian Atg9, a multi-spanning transmembrane protein, is one of the possible keys to understanding how autophagosomes are formed. Current and future advances in understanding the function of mammalian Atg9 will provide a basis for further progress. In addition, the identification of so far uncharacterized transmembrane proteins which are involved in autophagy will also help to address the important questions of where, how, and why autophagosomes form. PMID- 20350613 TI - Identification of modules in Aspergillus niger by gene co-expression network analysis. AB - The fungus Aspergillus niger has been studied in considerable detail with respect to various industrial applications. Although its central metabolic pathways are established relatively well, the mechanisms that control the adaptation of its metabolism are understood rather poorly. In this study, clustering of co expressed genes has been performed on the basis of DNA microarray data sets from two experimental approaches. In one approach, low amounts of inducer caused a relatively mild perturbation, while in the other approach the imposed environmental conditions including carbon source starvation caused severe perturbed stress. A set of conserved genes was used to construct gene co expression networks for both the individual and combined data sets. Comparative analysis revealed the existence of modules, some of which are present in all three networks. In addition, experimental condition-specific modules were identified. Module-derived consensus expression profiles enabled the integration of all protein-coding A. niger genes to the co-expression analysis, including hypothetical and poorly conserved genes. Conserved sequence motifs were detected in the upstream region of genes that cluster in some modules, e.g., the binding site for the amino acid metabolism-related transcription factor CpcA as well as for the fatty acid metabolism-related transcription factors, FarA and FarB. Moreover, not previously described putative transcription factor binding sites were discovered for two modules: the motif 5'-CGACAA is overrepresented in the module containing genes encoding cytosolic ribosomal proteins, while the motif 5' GGCCGCG is overrepresented in genes related to 'gene expression', such as RNA helicases and translation initiation factors. PMID- 20350614 TI - The development-specific ssp1 and ssp2 genes of Sclerotinia sclerotiorum encode lectins with distinct yet compensatory regulation. AB - The Ssp1 development-specific protein is the most abundant soluble protein in sclerotia and apothecia of Sclerotinia sclerotiorum. Although closely associated with these developmental stages, the functions of the Ssp1 protein and its paralog, Ssp2, are not known. In this study, protein structure prediction analysis revealed that Ssp1 and Ssp2 are structurally similar to fucose-specific lectins. In an effort to understand the function of these abundant, development specific proteins, a homokaryotic ssp1 deletion mutant was generated. The resulting mutant (Deltassp1) displays a wild-type growth and development phenotype in culture but produces approximately 50% fewer sclerotia in cultures supplemented with hygromycin. Genetic complementation with a wild-type copy of ssp1 restores normal sclerotium formation in the presence of hygromycin. This suggests that Ssp1 might play a role in resistance to glycoside-containing antibiotics encountered in the environment. Although a slight delay in carpogenic germination was observed, no additional effects of ssp1 loss-of-function were found in regards to apothecial morphology or fecundity. When the expression of ssp2 was examined in the Deltassp1 mutant, it was found to be expressed earlier in sclerotial development and its encoded protein accumulated to higher levels in both sclerotia and apothecia. These findings suggest regulatory compensation for loss of Ssp1 coupled with potential functional redundancy among lectins accumulating in sclerotia and apothecia. PMID- 20350615 TI - Identification of protein carbonyls in serum of the fetal and neonatal pig. AB - Oxidation of serum proteins leads to non-reversible carbonyl formation which alters their function and is associated with stress-related disease processes. The primary objective of this study was to quantify and identify oxidized serum proteins in fetal and newborn piglets. Protein carbonyls were converted to hydrazones with dinitrophenyl hydrazine and quantified spectrophotometrically. For identification, serum protein carbonyls were derivatized with biotin hydrazide, separated by 2D PAGE and stained with FITC-avidin. Biotin-labeled proteins were excised from gels and identified by mass spectrometry. At birth, carbonyls were determined to be approximately 600 pmole/mg serum protein. Fetuses at 50 and 100 days of gestation had similar levels of protein carbonyls as newborns. Carbonyl levels were also similar for control and runt (<1 kg at birth) piglets between 1 and 21 days of age; however, distribution of many proteins varied by age and was also influenced by birth weight. Major oxidized proteins identified in fetal (f) and newborn (n) pigs included; albumin (f, n), transferrin (f, n), fetuin-A (f, n) alpha fetoprotein (f, n), plasminogen (f, n), fetuin-B (f), alpha-1-antitrypsin (f, n) alpha-1-acid glycoprotein (f) and immunoglobulins (n). While abundance and distribution of oxidized proteins changed over time, these changes appear to primarily reflect relative amounts of those proteins in serum. PMID- 20350616 TI - Molecular cloning and antimicrobial activity of bombolitin, a component of bumblebee Bombus ignitus venom. AB - Bombolitin is the most abundant component of bumblebee venom and shares structural and biological properties with melittin, a component of honeybee venom. Here, we describe the molecular cloning and antimicrobial activity of bombolitin isolated from the venom of the bumblebee Bombus ignitus. The B. ignitus bombolitin gene consists of 2 exons encoding 56-amino acid residues. The bombolitin isolated from B. ignitus venom is a 1.99 kDa mature peptide with 18 amino acid residues, and it is created by the cleavage of the probombolitin domain between Ala38 and Leu39. B. ignitus bombolitin exhibits venom gland specific expression. We also investigated the antimicrobial properties of B. ignitus bombolitin against bacteria and fungi. The B. ignitus bombolitin showed high antibacterial activity against two Gram-positive and two Gram-negative bacteria. In addition, the B. ignitus bombolitin displayed antifungal activity against the plant pathogenic fungi Fulvia fulva and Alternaria radicina. PMID- 20350617 TI - Protein interaction network underpins concordant prognosis among heterogeneous breast cancer signatures. AB - Characterizing the biomolecular systems' properties underpinning prognosis signatures derived from gene expression profiles remains a key clinical and biological challenge. In breast cancer, while different "poor-prognosis" sets of genes have predicted patient survival outcome equally well in independent cohorts, these prognostic signatures have surprisingly little genetic overlap. We examine 10 such published expression-based signatures that are predictors or distinct breast cancer phenotypes, uncover their mechanistic interconnectivity through a protein-protein interaction network, and introduce a novel cross-"gene expression signature" analysis method using (i) domain knowledge to constrain multiple comparisons in a mechanistically relevant single-gene network interactions and (ii) scale-free permutation re-sampling to statistically control for hubness (SPAN - Single Protein Analysis of Network with constant node degree per protein). At adjusted p-values<5%, 54-genes thus identified have a significantly greater connectivity than those through meticulous permutation re sampling of the context-constrained network. More importantly, eight of 10 genetically non-overlapping signatures are connected through well-established mechanisms of breast cancer oncogenesis and progression. Gene Ontology enrichment studies demonstrate common markers of cell cycle regulation. Kaplan-Meier analysis of three independent historical gene expression sets confirms this network-signature's inherent ability to identify "poor outcome" in ER(+) patients without the requirement of machine learning. We provide a novel demonstration that genetically distinct prognosis signatures, developed from independent clinical datasets, occupy overlapping prognostic space of breast cancer via shared mechanisms that are mediated by genetically different yet mechanistically comparable interactions among proteins of differentially expressed genes in the signatures. This is the first study employing a networks' approach to aggregate established gene expression signatures in order to develop a phenotype/pathway based cancer roadmap with the potential for (i) novel drug development applications and for (ii) facilitating the clinical deployment of prognostic gene signatures with improved mechanistic understanding of biological processes and functions associated with gene expression changes. http://www.lussierlab.org/publication/networksignature/. PMID- 20350618 TI - Comparable renovascular protective effects of moxonidine and simvastatin in rats exposed to cigarette smoke. AB - Renovascular impairment plays a major role in smoking-induced nephrotoxicity. This study investigated the effect of the imidazoline I(1)-receptor/alpha(2) adrenoceptor agonist moxonidine, as compared to the lipid lowering drug simvastatin, on abnormalities induced by cigarette smoke (CS) in renovascular reactivity. Six rat groups were used: control, CS (twice a day for 6weeks), simvastatin, moxonidine, CS+simvastatin, and CS+moxonidine. CS exposure increased plasma urea and creatinine and reduced plasma and renal nitrate/nitrite (NOx). In isolated perfused phenylephrine-preconstricted kidneys of CS rats, vasodilator responses to carbachol or isoprenaline, but not papaverine, were attenuated. Nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine (L-NNA) reduced carbachol vasodilations in control but not CS kidneys, suggesting the impairment of NOS activity by CS. Simultaneous administration of moxonidine or simvastatin abolished CS-induced abnormalities in indices of renal function, NOx, and vasodilations caused by carbachol or isoprenaline. The possibility whether alterations in antioxidant or lipid profiles contributed to the interaction was investigated. CS increased renal malondialdyde and decreased glutathione, and glutathione peroxidase, superoxide dismutase and catalase activities. Further, CS reduced plasma HDL and increased cholesterol, triglycerides, and LDL. Simvastatin or moxonidine abolished the deleterious CS effects on antioxidant activity; the lipid profile was normalized by simvastatin only. These findings highlight that renovascular dysfunction caused by CS and the underlying oxidative damage is evenly attenuated by moxonidine and simvastatin. PMID- 20350620 TI - Evaluation of mesoporous silicon/polycaprolactone composites as ophthalmic implants. AB - The suitability of porous silicon (pSi) encapsulated in microfibers of the biodegradable polymer polycaprolactone (PCL) for ophthalmic applications was evaluated, using both a cell attachment assay with epithelial cells and an in vivo assessment of biocompatibility in rats. Microfibers of PCL containing encapsulated pSi particles at two different concentrations (6 and 20 wt.%) were fabricated as non-woven fabrics. Given the dependence of Si particle dissolution kinetics on pSi surface chemistry, two different types of pSi particles (hydride terminated and surface-oxidized) were evaluated for each of the two particle concentrations. Significant attachment of a human lens epithelial cell line (SRA 01/04) to all four types of scaffolds within a 24h period was observed. Implantation of Si fabric samples beneath the conjunctiva of rat eyes for 8 weeks demonstrated that the composite materials did not cause visible infection or inflammation, and did not erode the ocular surface. We suggest that these novel composite materials hold considerable promise as scaffolds in tissue engineering with controlled release applications. PMID- 20350621 TI - Extracellular microbial synthesis of biocompatible CdTe quantum dots. AB - An efficient bacterial synthesis method to harvest cadmium telluride (CdTe) quantum dots (QDs) with tunable fluorescence emission using Escherichia coli is demonstrated. Ultraviolet-visible, photoluminescence, X-ray diffraction and transmission electron microscopy analysis confirmed the superior size-tunable optical properties, with fluorescence emission from 488 to 551 nm, and the good crystallinity of the as synthesized QDs. A surface protein capping layer was confirmed by hydrodynamic size, zeta potential and Fourier transform infrared spectroscopy measurements, which could maintain the viability (92.9%) of cells in an environment with a QD concentration as high as 2 microM. After functionalization with folic acid the QDs were used to image cultured cervical cancer cells in vitro. Investigations of bacterial growth and morphology and the biosynthesis of CdTe QDs in Luria-Bertani medium containing E. coli-secreted proteins showed that extracellular synthesis directly relied on the E. coli secreted proteins, and a mechanism for protein-assisted biosynthesis of QDs is proposed. This work provides an economical approach to fabricate highly fluorescent biocompatible CdTe QDs via an environmentally friendly production process. The biosynthesized QDs may have great potential in broad bio-imaging and bio-labeling applications. PMID- 20350619 TI - Integrating depression and chronic disease care among patients with diabetes and/or coronary heart disease: the design of the TEAMcare study. AB - Diabetes and coronary heart disease (CHD) are two of the most prevalent medical illnesses in the US population and comorbid depression occurs in up to 20% of these patients. Guidelines for management of diabetes and CHD overlap for healthy lifestyle and disease-control recommendations. However, the majority of patients with these medical illnesses have been shown to have inadequate control of key risk factors such as blood pressure, LDL cholesterol, or blood sugar. Comorbid depression has been shown to adversely affect self-care of diabetes and CHD, and is associated with an increased risk of complications and mortality. Interventions that have improved quality and outcomes of depression care alone in patients with diabetes and CHD have not demonstrated benefits in self-care, improved disease control or morbidity and mortality. This paper describes the design and development of a new biopsychosocial intervention (TEAMcare) aimed at improving both medical disease control and depression in patients with poor control of diabetes and/or CHD who met the criteria for comorbid depression. A team approach is used with a nurse interventionist who receives weekly psychiatric and primary care physician caseload supervision in order to enhance treatment by the primary care physician. This intervention is being tested in an NIMH-funded randomized controlled trial in a large integrated health plan. PMID- 20350622 TI - Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass addition. AB - Thermally induced phase separation (TIPS) has proven to be a suitable method for the preparation of porous structures for tissue engineering applications, and particular attention has been paid to increasing the pore size without the use of possible toxic surfactants. Within this context, an alternative method to control the porosity of polymeric scaffolds via the combination with a bioglass is proposed in this work. The addition of a bioactive glass from the 3CaO x P2O5-MgO SiO2 system enables the porous structure of high molecular weight poly(l-lactic) acid (PLLA) scaffolds prepared by TIPS to be tailored. Bioglass acts as a nucleating catalyst agent of the PLLA matrix, promoting its crystallization, and the glass solubility controls the pore size. A significant increase in the pore size is observed as the bioglass content increases and scaffolds with large pore size (approximately 150 microm) can be prepared. In addition, the bioactive character of the scaffolds is proved by in vitro tests in synthetic plasma. The importance of this approach resides on the combination of the ability to tailor the porosity of polymeric scaffolds via the tunable solubility of bioglasses, without the use of toxic surfactants, leading to a composite structure with suitable properties for bone tissue engineering applications. PMID- 20350623 TI - Non-mosaic trisomy 20 of paternal origin in chorionic villus and amniotic fluid also detected in fetal blood and other tissues. AB - Trisomy 20 mosaicism is a common abnormality found in prenatal diagnosis. Its clinical significance remains unclear since approximately 90-93% of cases result in normal phenotype. Only 5 cases of non-mosaic trisomy 20 in amniotic fluid culture surviving beyond the first trimester have been reported. Moreover, trisomic cells are generally not detectable in blood and have only been reported in three cases. We present a case of non-mosaic trisomy 20 found in chorionic villi sample and amniotic fluid culture in a fetus with minor abnormalities not detected by ultrasound examination. Pathological examination of the fetus only revealed right pulmonary isomerism and camptodactily, and no major malformations were disclosed. Trisomic lineage was also detected in fetal blood, kidney, skin and brain tissue cultures. Molecular analysis revealed that the extra chromosome 20 was originated in paternal meiosis. To our knowledge, we report the first prenatal case of non-mosaic trisomy 20 of paternal origin that has been confirmed in several fetal tissues, including blood, in a fetus with minor malformations not detected prenatally. PMID- 20350624 TI - Co-expression of Flt-3 ligand gene ablates tumor immunity elicited by HER-2/neu DNA vaccine in transgenic mice. AB - Fms-like tyrosine-kinase 3 ligand (Flt-3L), is a powerful hematopoyetic growth factor, known to modulate the immune response against delivered antigens by acting either as an adjuvant or tolerogenic stimulus. In this study we evaluated the use of murine Flt-3 ligand plasmid (pFl) in combination with a DNA vaccine encoding rat-p185 oncoprotein extra cellular domain (pECD) in the prevention of mammary carcinogenesis in rat-neu HER-2 mutated (neuT) transgenic mice. We demonstrate that intramuscular (i.m.) co-immunization of pFl inhibits the production of anti-HER-2 antibody elicited by pECD vaccine, resulting in the development of spontaneous carcinomas in all co-immunized mice. The inhibitory effect on antibody production by mFlt3 gene appeared to be: dose-dependent, linked to the injection site and timing, and transient in nature. Additionally, we show that co-administration of pFI and pECD plasmids was unable to trigger cytotoxic T-cell immune response in neuT mice. On the other hand, we found that the combination of pFl with pECD had no impact on the ability of pECD to reject HER-2+ transplantable tumors in parental mice. In summary our results demonstrate that, depending on tumor model, co-administration of pFl gene can produce untoward effects to immune response, and thus its application as a vaccine adjuvant should be carefully evaluated. PMID- 20350625 TI - Antibodies and peptides in nuclear medicine imaging and therapy. Letter from the editors. PMID- 20350626 TI - Antibody vectors for imaging. AB - Noninvasive molecular imaging approaches include nuclear, optical, magnetic resonance imaging, computed tomography, ultrasound, and photoacoustic imaging, which require accumulation of a signal delivered by a probe at the target site. Monoclonal antibodies are high affinity molecules that can be used for specific, high signal delivery to cell surface molecules. However, their long circulation time in blood makes them unsuitable as imaging probes. Efforts to improve antibodies pharmacokinetics without compromising affinity and specificity have been made through protein engineering. Antibody variants that differ in antigen binding sites and size have been generated and evaluated as imaging probes to target tissues of interest. Fast clearing fragments, such as single-chain variable fragment (scFv; 25 kDa), with 1 antigen-binding site (monovalent) demonstrated low accumulation in tumors because of the low exposure time to the target. Using scFv as building block to produce larger, bivalent fragments, such as scFv dimers (diabodies, 50 kDa) and scFv-fusion proteins (80 kDa minibodies and 105 kDa scFv-Fc), resulted in higher tumor accumulation because of their longer residence time in blood. Imaging studies with these fragments after radiolabeling have demonstrated excellent, high-contrast images in gamma cameras and positron emission tomography scanners. Several studies have also investigated antibody fragments conjugated to fluorescence (near infrared dyes), bioluminescence (luciferases), and quantum dots for optical imaging and iron oxides nanoparticles for magnetic resonance imaging. However, these studies indicate that there are several factors that influence successful targeting and imaging. These include stability of the antibody fragment, the labeling chemistry (direct or indirect), whether critical residues are modified, the number of antigen expressed on the cell, and whether the target has a rapid recycling rate or internalizes upon binding. The preclinical data presented are compelling, and it is evident that antibody-based molecular imaging tracers will play an important future role in the diagnosis and management of cancer and other diseases. PMID- 20350627 TI - Immuno-positron emission tomography in cancer models. AB - Positron emission tomography (PET) is playing an increasingly important role in the diagnosis, staging, and monitoring response to treatment in a variety of cancers. Recent efforts have focused on immuno-PET, which uses antibody-based radiotracers, to image tumors based on expression of tumor-associated antigens. It is postulated that the specificity afforded by antibody targeting should both improve tumor detection and provide phenotypic information related to primary and metastatic lesions that will guide therapy decisions. Advances in antibody engineering are providing the tools to develop antibody-based molecules with pharmacokinetic properties optimized for use as immuno-PET radiotracers. Coupled with technical advances in the design of PET scanners, immuno-PET holds promise to improve diagnostic imaging and to guide the use of targeted therapies. An overview of the preclinical immuno-PET studies in cancer models is reviewed here. PMID- 20350630 TI - Preclinical and clinical studies of peptide receptor radionuclide therapy. AB - In the 1980s, the (111)In-labeled somatostatin analog OctreoScan (Covidien, Hazelwood, MO) was developed for imaging of somatostatin receptor subtype 2 (sst(2)) overexpressing tumors. On the basis of this success, peptide receptor radionuclide therapy (PRRT) was developed using similar somatostatin analogs with different therapeutic radionuclides. Clinical application of PRRT demonstrated impressive results on tumor response, overall survival, and quality of life in patients with gastroenteropancreatic neuroendocrine tumors. The peptides 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), Tyr(3)-octreotate (DOTATATE) and DOTA, Tyr(3)-octreotide (DOTATOC) (brand name Onalta), predominantly targeting sst(2), have been granted Orphan Drug status by the European Medicines Agency and the US Food and Drug Administration for application in PRRT. Besides somatostatin receptor-targeting peptides, multiple other radiopeptide analogs were developed targeting several other receptors overexpressed on various tumors. Some of these peptide analogs, including cholecystokinin, gastrin, gastrin-releasing peptide, arginine-glycine-aspartate (RGD)-peptides, and glucagon-like peptide 1 analogs appeared very promising in preclinical and clinical imaging and PRRT studies. Although the success of PRRT with radiolabeled somatostatin analogs has been established, there is still room for improvement. The therapeutic window of PRRT could be enlarged by the use of new and improved targeting compounds, of which new antagonists with excellent tumor to background ratios are very promising. Furthermore, locoregional administration, improved healthy tissue protection, and combination treatment can be applied to increase the effectiveness of PRRT. Combination treatment might include cocktails of different peptide analogs of different therapeutic radionuclides and of radiolabeled peptides with chemotherapeutic or radiosensitizing agents. This review summarizes results of PRRT and describes clinical and preclinical studies regarding PRRT optimizing strategies. PMID- 20350629 TI - Cancer therapy with alpha-emitters labeled peptides. AB - Actively targeted alpha-particles offer specific tumor cell killing action with less collateral damage to surrounding normal tissues than beta-emitters. During the last decade, radiolabeled peptides that bind to different receptors on the tumors have been investigated as potential therapeutic agents both in the preclinical and clinical settings. Advantages of radiolabeled peptides over antibodies include relatively straightforward chemical synthesis, versatility, easier radiolabeling, rapid clearance from the circulation, faster penetration and more uniform distribution into tissues, and less immunogenicity. Rapid internalization of the radiolabeled peptides with equally rapid re-expression of the cell surface target is a highly desirable property that enhances the total delivery of these radionuclides into malignant sites. Peptides, such as octreotide, alpha-melanocyte-stimulating hormone analogues, arginine-glycine aspartic acid-containing peptides, bombesin derivatives, and others may all be feasible for use with alpha-emitters. The on-going preclinical work has primarily concentrated on octreotide and octreotate analogues labeled with Bismuth-213 and Astatine-211. In addition, alpha-melanocyte-stimulating hormone analogue has been labeled with Lead-212/Bismuth-212 in vivo generator and demonstrated the encouraging therapeutic efficacy in treatment of experimental melanoma. Obstacles that continue to obstruct widespread acceptance of alpha-emitter-labeled peptides are primarily the supply of these radionuclides and concerns about potential kidney toxicity. New sources and methods for production of these medically valuable radionuclides and better understanding of mechanisms related to the peptide renal uptake and clearance should speed up the introduction of alpha emitter-labeled peptides into the clinic. PMID- 20350631 TI - Respiratory infections in the community: evaluating current antibiotic options. Introduction. PMID- 20350628 TI - Recombinant bispecific monoclonal antibodies prepared by the dock-and-lock strategy for pretargeted radioimmunotherapy. AB - The selective delivery of therapeutic radionuclides is a promising approach for treating cancer. Antibody-targeted radionuclides are of particular interest, with 2 products approved for the treatment of certain forms of non-Hodgkin lymphoma. However, for many other cancers, radioimmunotherapy has been ineffective, being limited by prolonged exposure to the highly radiosensitive bone marrow. An alternative approach, known as pretargeting, separates radionuclide from the antibody, allowing the radiation to be delivered on a small molecule that can quickly and efficiently migrate into the tumor, and then rapidly clear from the body with minimal retention in tissues. Several pretargeting methods have been developed that differ in the way they selectively capture the radionuclide. This review focuses on the development of a novel form of bispecific monoclonal antibody (bsMAb) pretargeting that uses a unique radiolabeled hapten-peptide system that can be modified to bind numerous therapeutic and imaging radionuclides. Together with a specialized recombinant humanized bsMAb prepared with by a technique known as the Dock-and-Lock method, this pretargeting procedure has been examined in many different animal models, showing a high level of sensitivity and specificity for localizing tumors, and improved efficacy with less hematologic toxicity associated with directly radiolabeled IgG. The bsMAb is a tri-Fab structure, having 2 binding arms for the tumor antigen and 1 capable of binding a hapten-peptide. Preclinical studies were preformed to support the clinical use of a bsMAb and a hapten-peptide bearing a single DOTA moiety (IMP 288). A phase 0 trial found an (131)I-tri-Fab bsMAb, TF2, that targets carcinoembryonic antigen was stable in vivo, quickly clears from the blood, and localizes known tumors. The first-in-patient pretargeting experience with the (111)In-IMP-288 also observed rapid clearance and low tissue (kidney) retention, as well as localization of tumors, providing initial promising evidence for developing these materials for radioimmunotherapy. PMID- 20350632 TI - Upper respiratory infections. AB - It is estimated that >24 million cases of acute bacterial sinusitis occur annually in the United States. Recently, a number of medical societies have issued guidelines to aid in the management of upper respiratory tract infections (URIs). Although these guidelines serve to aid practitioners in the proper use of antibiotics, confusion remains regarding the disparity of guideline recommendations as well as some recommendations being outdated. This review presents 3 illustrative case studies designed to provide some clarity with regard to these guidelines. Case 1 is a typical presentation of a patient with worsening sinus conditions over the previous 2 weeks. Case 2 is a more challenging case of a patient with a sinus condition accompanied by a penicillin allergy that ultimately requires referral to an otolaryngologist. Case 3 is an atypical case with symptoms of a sinus infection accompanied by a normal sinus computed tomography scan. It is hoped that the presentation and discussion surrounding these cases will provide some helpful insights into the management of patients with URIs. PMID- 20350633 TI - Safety and tolerability of commonly prescribed oral antibiotics for the treatment of respiratory tract infections. AB - Recent data suggest that adverse events (AEs) associated with the use of antimicrobial drugs are a major safety concern, with antibiotics implicated in a significant proportion (approximately 20%) of all drug-related emergency department visits in the United States. Although most of these visits are attributable to allergic reactions (79%), certain commonly prescribed antibiotics are notable contributors to conditions that range in nature from gastrointestinal to neurologic and/or psychiatric--particularly after ED visits are adjusted per outpatient prescription visits. This article reviews medically significant AEs of agents included in the major antimicrobial classes--AEs that may be underappreciated by general practitioners. Considerable attention is devoted to the fluoroquinolone agents. Also discussed are the assessment procedures of regulatory agencies in Europe and the United States that are in place to evaluate antimicrobial safety more accurately. Offsetting potential risks and benefits associated with currently available antimicrobials in a climate in which new agents are desperately needed to combat continually evolving multiresistant pathogens remains an interesting dilemma in antimicrobial therapy. PMID- 20350634 TI - Health economics of use fluoroquinolones to treat patients with community acquired pneumonia. AB - Respiratory diseases account for approximately 10% of all hospital admissions in the United States. Pneumonia constitutes 35% of these cases, with an average length of stay (LOS) of 5.1 days. It is estimated that $8.4 billion to $10 billion of all annual US hospital expenditures are attributable to community acquired pneumonia (CAP). As such, medical decisions, including empiric antibiotic choice, potentially exert an impact on hospital LOS and associated costs. In this review, we focus on the empiric antibiotic choices and associated costs of treatment for hospitalized patients with CAP, focusing on the use of fluoroquinolone therapy as recommended by the CAP guidelines. PMID- 20350635 TI - Case studies of lower respiratory tract infections: community-acquired pneumonia. AB - Community-acquired pneumonia (CAP) is a common and potentially serious illness with significant human and economic costs to society. The recent collaborative statement from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) represents the most up-to-date evidence-based guidelines from North America, incorporating important advances in the management of patients with CAP. The cases presented in this review highlight many of the recent recommendations from the IDSA/ATS guidelines. PMID- 20350636 TI - Discussion: 'Abdominal sacrocolpopexy and urinary incontinence' by Elser et al. PMID- 20350637 TI - Concurrent puerperal hysterectomy with Ascaris lumbricoides infestation: coincidence or consequence? AB - The most common etiology of postpartum hemorrhage is uterine atony, although hematologic disorders may be present. A 36-year-old nulliparous woman underwent puerperal hysterectomy caused by uncontrolled postpartum hemorrhage. One day after discharge, she vomited in the emergency room a 24-cm long Ascaris lumbricoides. Infestation during gestation may cause hematologic disorders that could complicate pregnancy outcome. PMID- 20350638 TI - Psychiatric morbidity after termination of pregnancy for fetal anomaly. PMID- 20350640 TI - Pelvic floor ultrasound: a review. AB - Imaging currently plays a limited role in the investigation of pelvic floor disorders. It is obvious that magnetic resonance imaging has limitations in urogynecology and female urology at present due to cost and access limitations and due to the fact that it is generally a static, not a dynamic, method. However, none of those limitations apply to sonography, a diagnostic method that is very much part of general practice in obstetrics and gynecology. Translabial or transperineal ultrasound is helpful in determining residual urine; detrusor wall thickness; bladder neck mobility; urethral integrity; anterior, central, and posterior compartment prolapse; and levator anatomy and function. It is at least equivalent to other imaging methods in visualizing such diverse conditions as urethral diverticula, rectal intussusception, mesh dislodgment, and avulsion of the puborectalis muscle. Ultrasound is the only imaging method able to visualize modern mesh slings and implants and may predict who actually needs such implants. Delivery-related levator trauma is the most important known etiologic factor for pelvic organ prolapse and not difficult to diagnose on 3-/4-dimensional and even on 2-dimensional pelvic floor ultrasound. It is likely that this will be an important driver behind the universal use of this technology. This review gives an overview of the method and its main current uses in clinical assessment and research. PMID- 20350642 TI - Trends in postpartum hemorrhage: United States, 1994-2006. AB - OBJECTIVE: The purpose of this study was to estimate the incidence of postpartum hemorrhage (PPH) in the United States and to assess trends. STUDY DESIGN: Population-based data from the 1994-2006 National Inpatient Sample were used to identify women who were hospitalized with postpartum hemorrhage. Data for each year were plotted, and trends were assessed. Multivariable logistic regression was used in an attempt to explain the difference in PPH incidence between 1994 and 2006. RESULTS: PPH increased 26% between 1994 and 2006 from 2.3% (n = 85,954) to 2.9% (n = 124,708; P < .001). The increase primarily was due to an increase in uterine atony, from 1.6% (n = 58,597) to 2.4% (n = 99,904; P < .001). The increase in PPH could not be explained by changes in rates of cesarean delivery, vaginal birth after cesarean delivery, maternal age, multiple birth, hypertension, or diabetes mellitus. CONCLUSION: Population-based surveillance data signal an apparent increase in PPH caused by uterine atony. More nuanced clinical data are needed to understand the factors that are associated with this trend. PMID- 20350641 TI - 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. AB - OBJECTIVE: We sought to evaluate 17-alpha-hydroxyprogesterone caproate (17P) for prevention of preterm birth (PTB) in women with prior spontaneous PTB (SPTB) and cervical length (CL) <25 mm. STUDY DESIGN: We conducted planned secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-sponsored randomized trial evaluating cerclage for women with singleton gestations, prior SPTB (17-33 6/7 weeks), and CL <25 mm between 16-22 6/7 weeks. Women were stratified at randomization to intent to use or not use 17P. The effect of 17P was analyzed separately for cerclage and no-cerclage groups. Primary outcome was PTB <35 weeks. RESULTS: In 300 women, 17P had no effect on PTB <35 weeks in either cerclage (P = .64) or no-cerclage (P = .51) groups. Only PTB <24 weeks (odds ratio, 0.08) and perinatal death (odds ratio, 0.14) were significantly lower for those with 17P in the no-cerclage group. CONCLUSION: 17P had no additional benefit for prevention of PTB in women who had prior SPTB and got ultrasound-indicated cerclage for CL <25 mm. In women who did not get cerclage, 17P reduced previable birth and perinatal mortality. PMID- 20350643 TI - Frequent epidural dosing as a marker for impending uterine rupture in patients who attempt vaginal birth after cesarean delivery. AB - OBJECTIVE: The purpose of this study was to estimate the association between epidural dosing and the risk of uterine rupture in women who attempt vaginal birth after cesarean delivery (VBAC). STUDY DESIGN: A nested case-control study within a multicenter retrospective cohort of >25,000 women with previous cesarean delivery compared cases of uterine rupture with women without rupture (control subjects) while attempting VBAC with epidural anesthesia. Dose timing, frequency, and quantity were compared. Time-to-event analyses were performed to estimate the association between epidural dosing and risk for uterine rupture while accounting for labor duration. RESULTS: Of 804 women in the nested case-control study, 504 women (62.7%) had epidural anesthesia, with no statistical difference in epidural usage rates between cases and control subjects (70.4% vs 62.4%; P = .09). Cox regression analysis revealed a dose-response relationship between the number of epidural doses and uterine rupture risk: 1 dose (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.7), 2 doses (hazard ratio, 3.1; 95% CI, 2.2-6.2), 3 doses (hazard ratio, 6.7; 95% CI, 3.8-12.1), > or =4 doses (hazard ratio, 8.1; 95% CI, 5.4-18.2). CONCLUSION: Clinical suspicion for uterine rupture should be high in women who require frequent epidural dosing during a VBAC trial. PMID- 20350644 TI - Maternal and fetal oxidative stress and intrapartum term fever. AB - OBJECTIVE: The association between maternal chorioamnionitis and fetal oxidative stress has not been well established. STUDY DESIGN: A nested case control study was performed within a prospective cohort of term nulliparous women: 20 cases (intrapartum fever of >100.4 degrees F) and 20 afebrile controls. Oxidative stress was assessed using ThioGlo-1 (TG-1; Calbiochem, San Diego, CA) fluorescent sulfhydryl detection. Median levels (+/- interquartile range) of protein-thiol sulfhydryls were compared. RESULTS: In early labor, maternal oxidative stress (lower protein sulfhydryls) was significantly higher in those women who subsequently had intrapartum fever develop (79.87 +/- 22.88 vs 127.73 +/- 43.79 counts/second per microg protein; P < .001). In contrast, cord serum sulfhydryls were not different between groups (75.77 +/- 14.00 vs 75.04 +/- 17.83 counts/second per microg protein; P = .99) CONCLUSION: Our data suggest that the term human fetus is protected from maternal oxidative stress associated with intrapartum fever. However, maternal oxidative status in early labor is associated with subsequent intrapartum fever. Optimal fetal neuroprotection will require a more precise knowledge of pathogenic mechanisms. PMID- 20350645 TI - Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction. AB - OBJECTIVE: Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress. We aimed to assess telomere length in trophoblasts from pregnancies with those complications. STUDY DESIGN: Placental specimens from 4 groups of patients were studied: severe preeclampsia, intrauterine growth restriction, preeclampsia combined with intrauterine growth restriction, and uncomplicated (control). Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry. RESULTS: Telomere length was significantly lower in preeclampsia, intrauterine growth restriction, and preeclampsia plus intrauterine growth restriction placentas. More aggregates were found in preeclampsia, but not in intrauterine growth restriction placentas. Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups. CONCLUSION: Telomeres are shorter in placentas from preeclampsia and intrauterine growth restriction pregnancies. Increased telomere aggregate formation in preeclampsia but not in intrauterine growth restriction pregnancies, implies different placental stress related mechanisms in preeclampsia with or without intrauterine growth restriction. PMID- 20350646 TI - Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. AB - OBJECTIVE: Substrates of placental efflux transporters could compete for a single transporter, which could result in an increase in the transfer of each substrate to the fetal circulation. Our aim was to determine the role of placental transporters in the biodisposition of oral hypoglycemic drugs that could be used as monotherapy or in combination therapy for gestational diabetes. STUDY DESIGN: Inside-out brush border membrane vesicles from term placentas were used to determine the efflux of glyburide, rosiglitazone, and metformin by P glycoprotein, breast cancer resistance protein, and multidrug resistance protein. RESULTS: Glyburide was transported by multidrug resistance protein (43 +/- 4%); breast cancer resistance protein (25 +/- 5%); and P-glycoprotein (9 +/- 5%). Rosiglitazone was transported predominantly by P-glycoprotein (71 +/- 26%). Metformin was transported by P-glycoprotein (58 +/- 20%) and breast cancer resistance protein (25 +/- 14%). CONCLUSION: Multiple placental transporters contribute to efflux of glyburide, rosiglitazone, and metformin. Administration of drug combinations could lead to their competition for efflux transporters. PMID- 20350647 TI - Evidence of a gene-environment interaction that predisposes to spontaneous preterm birth: a role for asymptomatic bacterial vaginosis and DNA variants in genes that control the inflammatory response. AB - OBJECTIVE: We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response. STUDY DESIGN: Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536-single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth. RESULTS: For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9-4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction. CONCLUSION: These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis. PMID- 20350648 TI - Identification and characterization of proteins in amniotic fluid that are differentially expressed before and after antenatal corticosteroid administration. AB - OBJECTIVE: We sought to examine changes in the intraamniotic proteomic environment after the administration of antenatal corticosteroids to women with impending preterm delivery. STUDY DESIGN: Amniotic fluid samples were collected at the time of clinically indicated amniocentesis before and within 7 days of administration of antenatal corticosteroids for impending preterm delivery (n = 12). Proteins differentially expressed before and after corticosteroids were identified by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. They were isolated, characterized, and quantified by fast protein liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel tryptic digestion, immunodepletion assays, enzyme-linked immunosorbent assay, and electrospray ionization tandem mass spectrometry. RESULTS: Five protein peaks of interest were identified and characterized, all of which were significantly decreased after antenatal corticosteroid administration. These included 2 isoforms of transthyretin, albumin, prothrombin fragment 2, and lumican. CONCLUSION: Four proteins, identified and characterized in amniotic fluid, were differentially expressed with antenatal corticosteroid administration. These data may provide additional insight into the molecular mechanisms by which antenatal corticosteroids prevent neonatal complications. PMID- 20350649 TI - Genomic loss of imprinting in first-trimester human placenta. AB - OBJECTIVE: The purpose of this study was to investigate imprinting patterns in first-trimester human placentas. STUDY DESIGN: Using samples of 17 first trimester and 14 term placentas from uncomplicated pregnancies, we assessed loss of imprinting (LOI) at the RNA level in a panel of 14 genes that are known to be imprinted in the placenta with the use of a quantitative allele-specific reverse transcriptase polymerase chain reaction analysis of those genes that contained readout single nucleotide polymorphisms in their transcripts. RESULTS: There is significant LOI (ie, biallelic expression) in all 14 genes in first-trimester placentas. LOI was more variable and generally at lower levels at term. Although there is little difference in gene expression, the level of LOI is higher in the first-trimester placentas, compared with term placentas. CONCLUSION: Genomic imprinting appears to be a dynamic maturational process across gestation in human placenta. In contrast with prevailing theories, epigenetic imprints may continue to evolve past 12 weeks of gestation. PMID- 20350650 TI - Transfer of bisphenol A across the human placenta. AB - OBJECTIVE: The objective of the investigation was to study placental transfer and conjugation of bisphenol A (BPA) across the human placenta. STUDY DESIGN: Human placentae obtained from healthy term singleton pregnancies were utilized in a dual recirculating model of ex vivo placental perfusion. Seven placentae were perfused with BPA (10 ng/mL) added to the maternal perfusate for 180 minutes. Antipyrine and fluorescein isothiocyanate dextran were used as positive and negative controls, respectively, to validate integrity of the circuits. Concentrations of BPA and its conjugates were determined by liquid chromatography mass spectrometry. RESULTS: The transfer percentage for antipyrine and BPA were 25.5 +/- 1.13% and 27.0 +/- 1.88%, respectively, and the transfer index for BPA was 1.1 +/- 0.09 after 180 minutes of perfusion. Only 3.2 +/- 1.6% of BPA in the fetal compartment was in the conjugated form. CONCLUSION: Bisphenol A at low environmentally relevant levels can transfer across the human placenta, mainly in active unconjugated form. PMID- 20350652 TI - Topics in clinical pharmacology: renal, gastrointestinal, and pain management. PMID- 20350653 TI - Management of postoperative ileus. AB - Postoperative ileus is an abnormal pattern of gastrointestinal motility that is common after both abdominal and nonabdominal surgeries. There are many causes of ileus, including postoperative pain and the use of narcotics for analgesia, electrolyte imbalances, and manipulation of the bowel during surgery. Despite its prevalence, there is still no reliable treatment to prevent ileus or shorten its course. This article discusses the causes of postoperative ileus and the treatment options currently available. The literature on early refeeding, gum chewing, and the use of tube feeds is reviewed. In addition, new and experimental drugs currently in development are discussed. PMID- 20350654 TI - Outpatient management of chronic kidney disease: proteinuria, anemia and bone disease as therapeutic targets. AB - There is increasing emphasis on chronic kidney disease (CKD), owing to its prevalence and its association with cardiovascular risk. Important issues concerning treatment of CKD are delaying its progression, improving patients' quality of life, and decreasing related mortality. These issues can be addressed with certain therapeutic options, targeting proteinuria, anemia, and secondary hyperparathyroidism. The management options and possible benefits related to treatment of these complications of CKD are reviewed. PMID- 20350655 TI - Dilemmas in chronic/persistent pain management. AB - The burden of chronic/persistent pain is substantial for the patient and society as a whole. Although a variety of pharmacologic treatments are available, chronic/persistent pain remains inadequately treated. Many pharmacologic treatment options provide analgesic efficacy for 4 to 6 hours, requiring multiple doses for continuous pain relief. The inconvenience of multiple doses may prevent many patients from achieving adequate pain relief. Other limitations to the current pharmacologic treatment options include gastrointestinal effects, cardiovascular effects, and organ toxicity, as well as fear of abuse or addiction. The purpose of this review is to highlight the burden of chronic/persistent pain in today's society and discuss the limitations of short acting pharmacologic therapies used in the treatment of chronic/persistent pain. PMID- 20350656 TI - Rituximab: therapeutic benefit! Vitamin R? PMID- 20350657 TI - CD20 as a target for therapeutic type I and II monoclonal antibodies. AB - The last decade has seen the monoclonal antibody (mAb), rituximab, transform clinical management of many non-Hodgkin lymphomas and more recently provide new opportunities for controlling autoimmune conditions, such as rheumatoid arthritis. Although not yet fully determined, the explanation for this success appears to lie with the inherent properties of its target, CD20, which allow rituximab to recruit potent cytotoxic effectors with unusual efficiency. In this review we detail the properties of CD20 that make it such an effective therapeutic target and describe how different mAbs change the membrane distribution and internalization of CD20 and have distinct modes of cytotoxic activity. PMID- 20350658 TI - Rituximab: mechanism of action. AB - Rituximab is a mainstay in the therapy for a broad variety of B-cell malignancies. Despite its undeniable therapeutic value, we still do not fully understand the mechanisms of action responsible for rituximab's anti-tumor effects. Direct signaling, complement-mediated cytotoxicity (CMC), and antibody dependent cellular cytotoxicity (ADCC) all appear to play a role in rituximab efficacy. In vitro, animal model and clinical data addressing each of these mechanisms of action are reviewed, as are data speaking to the complexity of interactions between these mechanisms. Taken together, these data suggest different mechanisms are likely important in different scenarios. Study of the complex mechanisms of action that contribute to the clinical efficacy of rituximab have led to novel clinical trials including novel combinations, schedules, and generation of additional antibodies designed to have even greater effect. Such studies need to be accompanied by rigorous correlative analysis if we are to understand the importance of various mechanisms of action of rituximab and use that information to improve on what is already an indispensable component of therapy. PMID- 20350659 TI - Antigenic modulation and rituximab resistance. AB - Several types of B-cell lymphoma have been successfully treated with rituximab, and approval by the US Food and Drug Administration for use of rituximab in the treatment of rheumatoid arthritis has increased interest in targeting CD20 on B cells for other indications. Although large amounts of rituximab can be infused into humans with no apparent dose-limiting toxicity, recent evidence suggests that the body's effector mechanisms, including complement-mediated cytotoxicity and natural killer (NK) cell-mediated killing, can be saturated or exhausted at high burdens of rituximab-opsonized B cells. One of the consequences of this saturation phenomenon is that the opsonized B cells are instead processed by a different pathway mediated by FcgammaR on effector cells. In this alternative pathway, both rituximab and CD20 are removed ("shaved") from the B cells and are taken up by monocytes/macrophages. This process, formerly called antigenic modulation, appears to occur in several compartments in the body and may play a key role in the development of resistance to rituximab therapy. PMID- 20350661 TI - Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab. AB - Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy. PMID- 20350660 TI - Rituximab in indolent lymphomas. AB - Indolent non-Hodgkin lymphoma (NHL) comprises a group of incurable, generally slow-growing lymphomas highly responsive to initial therapy, with a relapsing and progressive course. Rituximab, an anti-CD20 antibody, has had a large impact on the treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials, as well as data from the National Cancer Institute, indicate that the overall survival (OS) of patients with indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, rituximab is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL; however, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to respond to prolonged rituximab therapy. PMID- 20350662 TI - Rituximab in high-grade lymphoma. AB - In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal dosage and schedule of rituximab has to be addressed in well-designed randomized trials. The outcome of patients relapsing after a rituximab-containing induction regimen is dismal even with high-dose therapy and autologous stem cell transplantation (ASCT). For these patients new modalities of second-line therapy are urgently warranted. PMID- 20350664 TI - Rituximab in autoimmune hematologic diseases: not just a matter of B cells. AB - Rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen, has been investigated extensively in autoimmune disorders. Following the encouraging results in immune thrombocytopenia (ITP), the use of this agent was explored in other autoimmune hematologic diseases, most notably autoimmune hemolytic anemia (AIHA) and thrombotic thrombocytopenic purpura (TTP), characterized by the presence of pathogenetic autoantibodies. Although randomized clinical trials are lacking, the cumulative data would suggest that rituximab has a beneficial role in their treatment. Response to B cell-depleting therapy is actually associated with a significant decrease of circulating autoantibodies. However, several lines of evidence indicate that the T-cell compartment may also be modulated by these interventions. The doses and the duration of rituximab treatment in patients with autoimmune diseases are still unclear. The incidence of severe side effects is low but not insignificant. In particular, the risk of systemic infections and viral reactivation is a major concern. PMID- 20350663 TI - Rituximab in chronic lymphocytic leukemia. AB - Rituximab is a class I chimeric anti-CD20 antibody that has shown efficacy in chronic lymphocytic leukemia (CLL), both as a single agent and in combination with traditional chemotherapies. The modest activity demonstrated in early studies evaluating rituximab in relapsed CLL was improved with higher doses or more dose-intensive regimens that overcame the unfavorable pharmacokinetic features commonly found in CLL. These studies led to a variety of combination trials of rituximab with chemotherapy, where both phase II and later phase III studies have shown great promise for the advancement of CLL therapy. Despite the therapeutic success of rituximab in CLL, studies demonstrating the definitive relative mechanism of tumor clearance are still lacking and this requires further investigation. In addition to being used as a therapy for CLL, rituximab is an effective treatment for autoimmune CLL complications such as hemolytic anemia and immune thrombocytopenia (ITP). Patients with CLL may experience early infusion related side effects that can be diminished with corticosteroid pretreatment and stepped-up dosing. Risk factors for infusion-related toxicity may relate to atypical CLL expressing bright CD20 antigen expression, although several different studies have not clearly implicated elevated white blood cell count as a risk factor. Other adverse events, including delayed cytopenias, reactivation of hepatitis B, and development of progressive multifocal leukoencephalopathy, are rare. Future efforts focusing on novel combination-based strategies will be required to fully appreciate the benefit of this therapy in CLL. PMID- 20350665 TI - Rituximab-associated neutropenia. AB - Several recent studies have reported the phenomenon of late-onset neutropenia occurring usually several months following the administration of rituximab or rituximab-based therapies. While it appears that late-onset neutropenia is usually not clinically significant and is self-limited, it is important to recognize its existence given the expanding use of rituximab in both hematologic and nonhematologic disorders. Late-onset neutropenia is intriguing biologically and while its pathogenesis and mechanism are not completely understood, many interesting hypotheses have been proposed to explain its occurrence. PMID- 20350666 TI - Rituximab-associated infections. AB - After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management. PMID- 20350667 TI - CD20-targeted therapy: the next generation of antibodies. AB - Targeting the CD20 antigen on B lymphocytes with the monoclonal antibody (MoAb) rituximab has greatly improved the outcome of patients with B-cell malignancies. Despite the success of rituximab, resistance occurs in about half of the patients, resulting in non-response to treatment or early relapse with the original disease. A better understanding of the mechanism of rituximab resistance has led to the development of novel, improved anti-CD20 antibodies. This review describes the development of CD20-targeted therapy from its historical background towards the next generation of anti-CD20 MoAbs and explains new strategies to overcome resistance. PMID- 20350668 TI - The association of chiropractic colleges educational conference and research agenda conference: 17 years of scholarship and collaboration. AB - This editorial presents a brief description of the Association of Chiropractic Colleges Educational Conference and Research Agenda Conference, the components of the conference, and long range goals of the peer-review committee. PMID- 20350669 TI - The effect of spinal manipulation on the efficacy of a rehabilitation protocol for patients with chronic neck pain: a pilot study. AB - OBJECTIVE: This pilot study sought to (1) determine whether a 4-week period of chiropractic care improved the ability of chronic neck pain patients to respond to an 8-week period of exercise rehabilitation and (2) determine effect sizes to use in sample size calculations for future studies. METHODS: Twenty male and female participants (age, 43 +/- 12 years; body mass index, 27 +/- 4.5 [mean +/- SD]) with chronic nonspecific neck pain were randomized into either a chiropractic care combined with exercise or an exercise only group. Group 1 received 4 weeks of chiropractic care, and group 2 waited 4 weeks before both groups participated in an 8-week exercise intervention. The following outcome measures were assessed in week 1 (baseline), week 4, and at week 12: Neck Disability Index (NDI); Visual Analogue Scale (VAS), both now and worst; neck flexion-relaxation response; and feed-forward activation (FFA) times. A repeated measures analysis of variance was used to evaluate the changes in the NDI and VAS over time. Effect sizes were calculated for changes in neuromuscular parameters. RESULTS: There were significant decreases in the NDI score (P < .001) and VAS in (P < .005) in both groups with no significant differences between the groups. Effect sizes (ESs) were as follows: NDI (.293); VAS now (.175); VAS worst (.392); flexion-relaxation (.636); FFA times: sternocleidomastoid (.1321), anterior scalene (.195). This lead to sample size estimates as follows: flexion-relaxation response, 64 subjects per group; NDI, 145 subjects per group; VAS, 166 subjects per group. CONCLUSIONS: Chiropractic care combined with exercise and exercise alone are both effective at reducing functional disability and pain in chronic nonspecific neck pain patients. Future studies will need at least 64 subjects per group to determine if there are differences between the groups and if these differences are attributable to changes in neuromuscular measures. PMID- 20350670 TI - Altered central integration of dual somatosensory input after cervical spine manipulation. AB - OBJECTIVE: The aim of the current study was to investigate changes in the intrinsic inhibitory interactions within the somatosensory system subsequent to a session of spinal manipulation of dysfunctional cervical joints. METHOD: Dual peripheral nerve stimulation somatosensory evoked potential (SEP) ratio technique was used in 13 subjects with a history of reoccurring neck stiffness and/or neck pain but no acute symptoms at the time of the study. Somatosensory evoked potentials were recorded after median and ulnar nerve stimulation at the wrist (1 millisecond square wave pulse, 2.47 Hz, 1 x motor threshold). The SEP ratios were calculated for the N9, N11, N13, P14-18, N20-P25, and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar (MU) stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median (M) and ulnar (U) nerves. RESULTS: There was a significant decrease in the MU/M + U ratio for the cortical P22-N30 SEP component after chiropractic manipulation of the cervical spine. The P22-N30 cortical ratio change appears to be due to an increased ability to suppress the dual input as there was also a significant decrease in the amplitude of the MU recordings for the same cortical SEP peak (P22-N30) after the manipulations. No changes were observed after a control intervention. CONCLUSION: This study suggests that cervical spine manipulation may alter cortical integration of dual somatosensory input. These findings may help to elucidate the mechanisms responsible for the effective relief of pain and restoration of functional ability documented after spinal manipulation treatment. PMID- 20350671 TI - Spinal manipulation impacts cervical spine movement and fitts' task performance: a single-blind randomized before-after trial. AB - OBJECTIVE: The objective of this study was to determine if active cervical range of motion (ROM) and Fitts' task movement time differences occurred after high velocity low-amplitude cervical spinal manipulation (SM) across various indexes of difficulty. METHODS: A single-blind randomized before-after trial was performed in a motor performance laboratory. Fifteen volunteers (21-42 years) with asymptomatic palpable intervertebral motion restriction at the C1-C2 level were randomly assigned to an SM group or to a no-intervention (NI) group. A single episode of upper cervical manipulation was performed on the SM group. Active cervical ROM and movement time were measured pre and posttreatment in the SM group and compared to similar measurements in the NI group. RESULTS: In the SM group, active cervical ROM into rotation increased after the intervention (pre, 74.75 degrees +/- 7.63 degrees ; post, 78.50 degrees +/- 7.23 degrees ; t (7) = 3.07; P < .02). During the second trial, significant group differences were present in the SM group for movement time in direction congruent conditions (F((8,48)) = 2.83; P < .02; eta(p)(2) = .320) and direction incongruent conditions (F((8,48)) = 2.31; P < .05; eta(p)(2) = .278) but not for the NI group. CONCLUSIONS: A linear relationship between indexes of difficulty and movement time as predicted by Fitts' law was observed. Significant group effects indicate that SM not only increases cervical active ROM but also facilitates the performance of a cervical spine Fitts' task requiring rotation. This task may be used to quantify motor performance in clinically symptomatic populations with reduced ROM who are appropriate candidates for SM. PMID- 20350672 TI - Mechanical vs manual manipulation for low back pain: an observational cohort study. AB - OBJECTIVE: This is an observational prospective cohort study to explore the treatment effect of mechanical vs manual manipulation for acute low back pain. METHODS: Ninety-two patients with a history of acute low back pain were recruited from 3 private chiropractic offices, 2 of which used manual lumbar manipulation and 1 used mechanical instrument manipulation (Activator) as their primary modes of treatment. The chiropractors used their "treatment-as-usual" protocols for a maximum of 8 visits or 4 weeks, whichever occurred first. Primary outcome measures were changes in Numeric Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI) scores from baseline to 4 weeks. The linear regression models were adjusted for baseline NPRS and ODI scores, age, and treatment expectancy. RESULTS: Comparison of baseline characteristics did not show any significant differences between the groups except for age (38.4 vs 49.7 years, P < .001) and treatment expectancy (5.7 vs 6.3, P = .003). Linear regression revealed significantly lower NPRS scores in the manual manipulation group at 4 weeks (beta = -1.2; 95% confidence interval, -2.1 to -.28) but no significant difference in ODI scores between the 2 groups at 4 weeks (beta = 1.5; 95% confidence interval, 8.3 to 2.4). Treatment expectancy, but not age, was found to have a significant main effect on both NPRS and ODI scores at 4 weeks. Exploratory analysis of the clinical patterns of care between the clinicians revealed significant differences in treatment frequency, duration, modality, and radiograph use between the 2 cohorts. CONCLUSIONS: This study highlights the challenges inherent with conducting research that allows for "treatment as usual." The data and experience derived from this investigational study will be used to design a future randomized clinical trial in which tighter controls will be imposed on the treatment protocol. PMID- 20350673 TI - Self-perceived skills confidence: an investigative study of chiropractic students in the early phases of a college's clinic program. AB - OBJECTIVE: This pilot study surveyed students at early stages of a chiropractic college's clinical curriculum, at the time when integration of patient evaluation and management begins to occur, for collecting data regarding perceived levels of confidence in their spinal analysis and adjusting (manipulation) skills. METHODS: An online, cross-sectional survey based on students' perceptions of their skills was conducted in a basic technique review class for 3 consecutive terms. Questions primarily focused on full-spine radiography (Gonstead-type) analysis, radiographic descriptive analysis, motion palpation analysis, and manual full spine and diversified spinal manipulation. RESULTS: Of 226 eligible students, 108 participated. The respondents were overall more confident with their analysis skills in full-spine radiographs and descriptive listings than they were with their motion palpation analysis. Self-confidence with spinal manipulation skills followed a general pattern from confident to unconfident to unsure. Students were most confident with prone thoracic spinal manipulation and least confident with seated cervical spinal manipulation. With lumbar and pelvic manipulation, confidence levels varied between side posture pushes, side posture pulls, and prone setups. CONCLUSIONS: Considerably more than half of the respondents were confident enough with their skills to feel comfortable beginning the clinical experience. PMID- 20350674 TI - Vertebral artery hypoplasia: prevalence and reliability of identifying and grading its severity on magnetic resonance imaging scans. AB - OBJECTIVE: The purpose of this study is to examine the inter- and intraexaminer reliability of determining the prevalence of vertebral artery hypoplasia on magnetic resonance imaging (MRI) as well as the reliability of assigning a severity grading of mild, moderate, or marked hypoplasia. METHODS: Two chiropractic radiologists independently evaluated the MR images of 131 adult patients retrospectively for visual vertebral artery hypoplasia. Severity of hypoplastic was graded. The side of hypoplasia and sex of the patient were recorded. The process was repeated after 1 month. Descriptive statistics were calculated for prevalence, severity, and sex distribution of hypoplasia. The kappa statistic was calculated for the reliability of detecting and grading the hypoplasia. RESULTS: Interexaminer reliability was substantial for both readings (kappa = 0.68, 83% agreement for the first reading; kappa = 0.75, 86% agreement for the second reading). Interexaminer reliability for grading the severity of asymmetry was substantial (kappa = 0.73, 83% agreement for the first read; kappa = 0.69, 81% agreement for the second reading). Intraexaminer reliability readings provided a kappa of 0.71 (substantial) and 83% agreement for examiner 1. Examiner 2 had a kappa of 0.85 (almost perfect) with 92% agreement. Overall, 57 (43.5%) of the 131 patients demonstrated hypoplasia. Hypoplasia was more common in women (49%) than men (35.8%). Seven arteries demonstrated severe hypoplasia. Six of these 7 patients were women. CONCLUSIONS: Vertebral artery hypoplasia is common and can be reliably diagnosed and categorized on cervical MRI scans. Vertebral artery hypoplasia was more common in women than men in this group of patients. PMID- 20350675 TI - Effects of ice massage on pressure pain thresholds and electromyography activity postexercise: a randomized controlled crossover study. AB - OBJECTIVE: The purpose of this study was to investigate the effects of ice massage postexercise on pressure pain thresholds (PPTs) over the quadriceps muscle and the electromyography (EMG) root mean square (RMS). METHODS: Fifteen athletes (female, 8; age, 19 +/- 2 years) participated. Subjects were required to visit the laboratory on 2 separate occasions with a 1-week interval between sessions. Participants performed 5 isokinetic concentric dominant knee extension contractions at 60 degrees , 120 degrees , 180 degrees , and 240 degrees /s. After exercise, they were randomly assigned to receive either an ice massage or detuned ultrasound for 15 minutes, 1 on each session. The PPT and RMS during maximal voluntary contraction were measured over the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles at baseline, postexercise, and 5 minutes postintervention. The hypothesis of interest was the intervention x time interaction. RESULTS: The analysis of covariance found a significant intervention x time interaction for PPT over the VM (F = 17.3, P < .001) and VL (F = 5.4, P = .03) muscles but not over the RF (F = 1.2, P = .3), indicating an increase in PPT after the ice massage. An intervention x time interaction was found for RMS of the VL (F = 5.8, P = .01) but not of the VM (F = 0.5, P = .5) or RF (F = 0.01, P = .9) muscles, indicating an increase in RMS after the ice massage. A significant positive correlation between PPT and RMS for the VL muscle was identified (r = 0.6, P = .03). CONCLUSION: Ice massage after isokinetic exercise produced an immediate increase of PPT over the VL and VM and EMG activity over the VL muscle in recreational athletes, suggesting that ice massage may result in a hypoalgesic effect and improvements in EMG activity. PMID- 20350677 TI - Learning spinal manipulation skills: assessment of biomechanical parameters in a 5-year longitudinal study. AB - OBJECTIVE: Teaching spinal manipulation (SM) is a fundamental aspect of chiropractic training. Recent works have identified various biomechanical variables as indicators of SM performance and learning. However, only data from cross-sectional studies are available, limiting conclusions regarding the persistence of SM performance over the years. Therefore, the main objective of this investigation was to quantify the evolution of biomechanical parameters of SM over a 5-year learning period. METHODS: Thirty-three students enrolled in a chiropractic program participated in the present study. They were tested each year at the beginning of each fall semester by performing 10 SMs on an instrumented manikin while standing on a force plate. The procedure allowed us to measure various force-time parameters. RESULTS: Overall, significant time effects were noted for most dependent variables. The results indicated rapid improvement in the peak force applied and the rate of force production during the first 2 years. Time to peak force decreased drastically during the first year, whereas preload forces reached satisfactory levels during the third year. When various force-time requirements of bimanual task components were met, learners significantly reduced trial-to-trial variability of SM peak and preload forces, indicating automaticity of performance. Although global coordination improved in all learning processes, it was only in the later phase that learners reached values approaching those of experts. CONCLUSION: Overall, these results highlighted the importance of considering learning principles in the development of didactic strategies related to SM motor skills. PMID- 20350676 TI - Reliability of zygapophysial joint space measurements made from magnetic resonance imaging scans of acute low back pain subjects: comparison of 2 statistical methods. AB - OBJECTIVE: This purpose of this study was to assess the reliability of measurements made of the zygapophysial (Z) joint space from the magnetic resonance imaging scans of subjects with acute low back pain using new equipment and 2 different methods of statistical analysis. If found to be reliable, the methods of Z joint measurement can be applied to scans taken before and after spinal manipulation in a larger study of acute low back pain subjects. METHODS: Three observers measured the central anterior-to-posterior distance of the left and right L4/L5 and L5/S1 Z joint space from 5 subject scans (20 digitizer measurements, rounded to 0.1 mm) on 2 separate occasions separated by 4 weeks. Observers were blinded to each other and their previous work. Intra- and interobserver reliability was calculated by means of intraclass correlation coefficients and also by mean differences using the methods of Bland and Altman (1986). A mean difference of less than +/-0.4 mm was considered clinically acceptable. RESULTS: Intraclass correlation coefficients showed intraobserver reliabilities of 0.95 (95% confidence interval, 0.87-0.98), 0.83 (0.62-0.92), and 0.92 (0.83-0.96) for each of the 3 observers and interobserver reliabilities of 0.90 (0.82-0.95), 0.79 (0.61-0.90), and 0.84 (0.75-0.90) for the first and second measurements and overall reliability, respectively. The mean difference between the first and second measurements was -0.04 mm (+/-1.96 SD = -0.37 to 0.29), 0.23 (-0.48 to 0.94), 0.25 (-0.24 to 0.75), and 0.15 (-0.44 to 0.74) for each of the 3 observers and the overall agreement, respectively. CONCLUSIONS: Both statistical methods were found to be useful and complementary and showed the measurements to be highly reliable. PMID- 20350678 TI - Medication prescription: a pilot survey of Bernese doctors of chiropractic practicing in Switzerland. AB - OBJECTIVE: The purpose of this survey was to assess the use of and the attitude toward prescribing medication among doctors of chiropractic in 1 of 26 Swiss cantons. METHODS: A Likert scale electronic questionnaire was sent to licensed doctors of chiropractic of the canton of Berne (n = 47). Percentages, mean values, and standard deviations were calculated. A follow-up survey was used to assess comments from the main survey. A probability value of P < .05 indicated a statistically significant difference. RESULTS: The response rate was 77%. Forty one percent of the respondents stated that medications are a necessary component of the chiropractic treatment. Although 92% actively prescribe medication at least once a week, this is significantly less than asked for by their patients (P < .01). Seventy-two percent of the doctors of chiropractic rated the present privilege to prescribe nonprescription medications as an advantage for chiropractic care. Fifty-eight percent thought that chiropractic should aim at expanding the options of nonsteroidal anti-inflammatory drugs, analgesics, and muscle relaxants that can be prescribed. Ninety-one percent agreed on continuing education in pharmacology. Despite prescribing medication at least once a week, less than half of Bernese doctors of chiropractic perceived medications as a necessary component of their treatment, mainly using them to help patients who cannot sleep because of pain and to speed up recovery. When asked if they would be allowed to prescribe medications of the "B-list," the majority would want structured continuing education. CONCLUSION: Limited medication prescription was judged as an advantage for the chiropractic profession by this group of survey participants. PMID- 20350679 TI - Consistency of cutaneous thermal scanning measures using prone and standing protocols: a pilot study. AB - OBJECTIVE: The goal of this pilot study was to measure paraspinal cutaneous temperature (PCT) in the prone vs standing position. METHODS: Ten symptom-free participants were evaluated. Paraspinal cutaneous temperature was recorded. Subjects were acclimated to the treatment room in a prone position for 8 minutes before the PCT was measured. After the prone PCT reading, patients stood. A standing PCT measurement was then taken. RESULTS: Paraspinal cutaneous temperature was marginally warmer when subjects were standing vs prone (PCT difference, 0.25 degrees C +/- 0.64 degrees C and 0.62 degrees C +/- 0.67 degrees C for left and right sides, respectively). The right and left side differential was the same in the prone and standing positions. There was a positive Pearson correlation (0.802-0.803; P < .000) between the standing and prone positions for both left and right sides. CONCLUSION: There are no differences between the prone or standing PCT measures if symptom-free subjects are given 8 minutes to acclimate before recording PCT measures. PMID- 20350680 TI - Characterization of focal liver lesions with contrast-enhanced ultrasound. AB - The introduction of second generation microbubble ultrasound (US) contrast agents, such as SonoVue (Bracco, Milan, Italy), has considerably improved the diagnostic yield of US imaging for the evaluation of focal hepatic lesions in recent years because of its ability to very sensitively depict tumoral vascularity. In addition, contrast-enhanced US (CEUS) has the advantage of the absence of ionizing radiation, the widespread availability, even at the bedside, and the possibility to characterize a lesion as soon as detected on conventional B-mode US, commonly used as the first technique for exploration of the liver. The present review focuses on the basic principles of the technique and the various patterns of benign and malignant hepatic lesions at CEUS, contributing to their characterization. Understanding of these enhancement features at CEUS according to the type of tumors enables to make more accurate characterization of focal liver lesions as well as give better advice to oncologists, hepatologists or other clinicians in case of suspected liver tumors. PMID- 20350681 TI - Malignant lesions initially categorized as probably benign breast lesions: retrospective review of ultrasonographic, clinical and pathologic characteristics. AB - The primary objective of this study was to review the ultrasonographic features of BI-RADS category 3 ("probably benign") lesions that eventually proved to be malignant. A second objective was to investigate their clinical and pathologic features according to their palpability and time of biopsy. Thirty-two (0.8%) of 4000 women with lesions that were initially classified as "probably benign" proved to be malignant and formed the study group. The most common reason for a false negative assessment on ultrasound was a failure to recognize suspicious margin characteristics (28 of 32 malignancies, 87.5%). Malignancy was more frequent in palpable (2.4%, 21 of 859) than nonpalpable lesions (0.4%, 11 of 3141, p < 0.001). There was no statistical difference in the mean age, mean size of lesions, or tumor stage between patients who underwent early biopsy (n = 19) or biopsy after 6 months (n = 13). Twenty-nine of the lesions (90.6%) were retrospectively recategorized as BI-RADS 4, which calls for early biopsy. BI-RADS 3 lesions require especially careful assessment. PMID- 20350683 TI - Common carotid artery duplex for the bubble test to detect right-to-left shunt. AB - We prospectively compared the bubble test with agitated saline for right-to-left shunt using transcranial Doppler (TCD) of the right middle cerebral artery and second harmonic imaging duplex of the right common carotid artery (CCA) in 100 consecutive patients. Microembolic signals (MES) were counted offline. MES were classified into 6 classes: absent (class 0), 1-10 MES (class 1), 11-20 MES (class 2), 21-30 MES (class 3), 31-50 MES (class 4) and >50 MES or "curtain effect" (class 5). For TCD, classes 2-5 combined (i.e., "large" shunts), the sensitivity of duplex with the Valsalva maneuver was 95.3%, the specificity was 100%, the positive predictive 100%, the negative predictive value 96.6% and accuracy 98.0%. Second harmonic imaging duplex of the CCA may substitute TCD for the bubble test when an adequate cranial bone window is not available. This technique may also greatly increase the number of facilities where the bubble test can be carried out. However, tests with few or no MES need to be confirmed by TCD or transesophageal echocardiography. PMID- 20350682 TI - Measurement of aortic intimal-medial thickness in adolescents and young adults. AB - Atherosclerosis begins in childhood in the distal abdominal aorta and later involves the carotid arteries. Noninvasive screening to detect these lesions may allow early intervention. Ultrasound images of the distal 10 mm of the aorta were obtained after an 8-h fast and were analyzed by an automated program to determine the mean far wall intimal-medial thickness (IMT). The results were compared with the mean carotid IMT obtained concurrently. The mean age of the 313 males and 322 females imaged was 20.4 years (SD 5.6) and 61 participants had a second study to assess reproducibility. The mean aortic IMT was 0.63 mm (SD 0.14) for males and 0.61 mm (SD 0.13) for females while the mean carotid IMT was 0.50 (SD 0.04) mm and 0.49 (SD 0.04) mm, respectively. Images were analyzed in 95% of participants. Intra-subject reproducibility for the mean aortic IMT had a coefficient of variation of 18% with a mean absolute difference of 0.12 mm (SD 0.10). For carotid IMT, the results were 3% and 0.02 mm (SD 0.01), respectively. Aortic IMT can be measured in normal adolescents and young adults with low rates of missing data and reasonable reproducibility. Aortic IMT increased with age at a greater rate than carotid IMT. PMID- 20350684 TI - Magnetic resonance imaging vs. transvaginal ultrasound for cervical length assessment in the second half of pregnancy. AB - The purpose of this cross-sectional study involving 42 women between 20 and 39 weeks gestation was to compare transvaginal ultrasound (TVUS) vs. magnetic resonance imaging (MRI) in the assessment of cervical length measurement during the second half of pregnancy and to evaluate the reproducibility of cervical measurements obtained through MRI. Cervical length was measured through TVUS by a single examiner. On the same day, all women also had MRI and cervical length was assessed by two independent blinded observers. There were no significant differences in the mean cervical length obtained through TVUS and MRI (paired t test, p = 0.191). The Bland-Altman test indicated concordance between measurements obtained through methods as well as good intra- and interobserver reproducibility for MRI measurements. Intraclass correlation coefficient was 0.990 (95% confidence interval [CI]: 0.982 to 0.995; p < 0.001) for measurements performed using MRI by two different observers and 0.995 (95% CI: 0.991 to 0.997; p < 0.001) for measurements performed using the same method by a single operator. Cervical length measured through TVUS and MRI does not differ significantly. There is a good reproducibility of cervical measurements obtained through MRI. PMID- 20350686 TI - Evaluation of cerebral blood flow changes in focal cerebral ischemia rats by using transcranial Doppler ultrasonography. AB - Ischemic stroke is typically characterized by the disruption of cerebral blood flow. This study aimed to consecutively evaluate the cerebral blood flow changes in a focal ischemia rat model during the occlusion-reperfusion procedure and along the recovery stage after stroke. In 12 Sprague Dawley (SD) rats, a middle cerebral artery occlusion/reperfusion (MCAo/r) surgery was conducted, which combines a permanent occlusion of the right common carotid artery (CCA), external carotid artery (ECA) and a transient occlusion of the right internal carotid artery (ICA) and middle cerebral artery (MCA) with a monofilament introduced from the proximal ICA towards the distal right ICA then removed after 90 min. Blood flow velocity (BFV) from the concerned arteries were measured using ultrasonography (13-4 MHz) at the basal stage before the surgery, after the reperfusion stage and during the post-stroke status. At reperfusion stage and after, BFV increased significantly in the left ICA and in the basilar artery (BA) (starting from post-24 h, p < 0.05 vs. basal). Moreover, BFV were reversed in the distal right ICA and reflow was recorded in the right MCA. Time-average maximum BFV in the right MCA at reperfusion and post-stroke 24-96 h was decreased significantly (p < 0.05 vs. basal). The reversed flow in the right ICA was enabled by the settlement of the collateral supply through the circle of Willis which consisted in higher BFV in the opposite ICA and in the BA still 24 h, although the proximal right ICA remain occluded. Ultrasound measurement of BFV helps to provide information on the redistribution of the blood flow supply after the onset of stroke. PMID- 20350685 TI - Acoustic radiation force impulse imaging of human prostates ex vivo. AB - It has been challenging for clinicians using current imaging modalities to visualize internal structures and detect lesions inside human prostates. Lack of contrast among prostatic tissues and high false positive or negative detection rates of prostate lesions have limited the use of current imaging modalities in the diagnosis of prostate cancer. In this study, acoustic radiation force impulse (ARFI) imaging is introduced to visualize the anatomical and abnormal structures in freshly excised human prostates. A modified Siemens Antares ultrasound scanner (Siemens Medical Solutions USA Inc., Malvern, PA) and a Siemens VF10-5 linear array were used to acquire ARFI images. The transducer was attached to a three dimensional (3-D) translation stage, which was programmed to automate volumetric data acquisition. A depth dependent gain (DDG) method was developed and applied to 3-D ARFI datasets to compensate for the displacement gradients associated with spatially varying radiation force magnitudes as a function of depth. Nine human prostate specimens were collected and imaged immediately after surgical excision. Prostate anatomical structures such as seminal vesicles, ejaculatory ducts, peripheral zone, central zone, transition zone and verumontanum were visualized with high spatial resolution and in good agreement with McNeal's zonal anatomy. The characteristic appearance of prostate pathologies, such as prostate cancerous lesions, benign prostatic hyperplasia, calcified tissues and atrophy were identified in ARFI images based upon correlation with the corresponding histologic slides. This study demonstrates that ARFI imaging can be used to visualize internal structures and detecting suspicious lesions in the prostate and appears promising for image guidance of prostate biopsy. PMID- 20350687 TI - Estimation of average speed of sound using deconvolution of medical ultrasound data. AB - In diagnostic ultrasound imaging the speed of sound is assumed to be 1540 m/s in soft tissues. When the actual speed is different, the mismatch can lead to distortions in the acquired images and so reduce their clinical value. Therefore, the estimation of the true speed has been pursued not only because it enables image correction but also as a way of tissue characterisation. In this article, we present a novel way to measure the average speed of sound concurrently with performing image enhancement by deconvolution. This simultaneous capability, based on a single acquisition of ultrasound data, has not been reported in previous publications. Our algorithm works by conducting non-blind deconvolution of the reflection data with point-spread functions based on different speeds of sound. Using a search strategy, we select the speed that produces the best possible restoration. The deconvolution operates on the beamformed uncompressed radio-frequency data, without any need to modify the hardware of the ultrasound machine. A conventional handling of the transducer array is all that is required in the data acquisition part of our proposed method: the data can be collected freehand, unlike most other estimation methods. We have tested our algorithm with simulations, in vitro phantoms with known and unknown speeds and in vivo scans. The estimation error was found to be +0.19 +/- 8.90 m/s (mean +/- standard deviation) for in vitro in-house phantoms whose speeds were also measured independently. In addition to the speed estimation, our method has also proved to be capable of simultaneously producing a better restoration of ultrasound images than deconvolution by an assumed speed of 1540 m/s, when this assumption is incorrect. PMID- 20350688 TI - Multimode ultrasound breast imaging using a new array transducer configuration. AB - This article presents a diagnostic ultrasound imaging technique that can be used in imaging protruding objects such as a human breast using two opposing array transducers. Because two B-mode images obtained from each of the two linear array transducers facing each other represent the same imaging area viewed in different directions, the image quality can be improved using a compounding technique. Using one array as a transmitter and the other as a receiver, the speed of sound distribution in a medium interposed between them is also reconstructed. In addition, because the spacing between the two arrays can be finely controlled, strain image can also be obtained. This new method can be used to produce a compound B-mode image, a speed of sound image, and a strain image of the same region-of-interest, making it possible to obtain more information leading to better diagnosis. Experimental results on a phantom containing a cylinder of different speed of sound and elasticity confirm that the proposed method is useful in obtaining compound and speed of sound images as well as strain images. PMID- 20350689 TI - The leicester Doppler phantom--a digital electronic phantom for ultrasound pulsed Doppler system testing. AB - Doppler flow and string phantoms have been used to assess the performance of ultrasound Doppler systems in terms of parameters such as sensitivity, velocity accuracy and sample volume registration. However, because of the nature of their construction, they cannot challenge the accuracy and repeatability of modern digital ultrasound systems or give objective measures of system performance. Electronic Doppler phantoms are able to make use of electronically generated test signals, which may be controlled precisely in terms of frequency, amplitude and timing. The Leicester Electronic Doppler Phantom uses modern digital signal processing methods and field programmable gate array technology to overcome some of the limitations of previously described electronic phantoms. In its present form, it is able to give quantitative graphical assessments of frequency response and range gate characteristics, as well as measures of dynamic range and velocity measurement accuracy. The use of direct acoustic coupling eliminates uncertainties caused by Doppler beam effects, such as intrinsic spectral broadening, but prevents their evaluation. PMID- 20350690 TI - Potential of first arriving signal to assess cortical bone geometry at the Hip with QUS: a model based study. AB - There is evidence that quantitative ultrasound (QUS) at the proximal femur involves waves propagating circumferentially in the cortical shell. These waves, in theory, convey information on bone geometrical and material characteristics and thus have the potential to improve fracture risk prediction. In this work, the time-of-flight (TOF) of the first arriving signal (FAS) that corresponds to waves propagating circumferentially is considered. The relationships between the TOF of the FAS and geometrical features of the femoral neck are investigated. Five neck cross-sections from 11 human femurs from females (>65y) were extracted from 3-D X-ray quantitative computed tomography (XR-QCT) datasets. Geometrical parameters including cross-sectional area (CSA), minimum moment of inertia (I(min)) and section modulus (Z) were computed from femoral neck cross-section images. Two-dimensional numerical simulation of US propagation through femoral neck was performed and TOF of the FAS was estimated. TOF was best correlated with I(min): R(2)=0.82 (p=10(-4); RMSE=1390mm(4) [13%]) in the region between proximal and mid-femoral neck and with Z: R(2)=0.55 (p<10(-2); RMSE=480mm(3) [17%]) and CSA: R(2)=0.62 (p<5.10(-3); RMSE=22mm(2) [7%]) in the mid-femoral neck. The results suggest that QUS has the potential to assess proximal femur strength based on estimates of geometrical properties of the cortical shell. PMID- 20350693 TI - Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD. AB - BACKGROUND: Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics. METHODS AND RESULTS: Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 +/- 3.1 UF, 3.6 +/- 3.5 continuous infusion, and 2.9 +/- 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 +/- 2.6 UF, 3.9 +/- 2.7 continuous infusion, and 3.1 +/- 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 +/- 1.36) than in continuous infusion (2.29 +/- 3.23; P = .016 versus UF) and bolus diuretics (1.31 +/- 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days. CONCLUSIONS: Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients. PMID- 20350691 TI - Changes in cell morphology due to plasma membrane wounding by acoustic cavitation. AB - Acoustic cavitation-mediated wounding (i.e., sonoporation) has great potential to improve medical and laboratory applications requiring intracellular uptake of exogenous molecules; however, the field lacks detailed understanding of cavitation-induced morphologic changes in cells and their relative importance. Here, we present an in-depth study of the effects of acoustic cavitation on cells using electron and confocal microscopy coupled with quantitative flow cytometry. High resolution images of treated cells show that morphologically different types of blebs can occur after wounding conditions caused by ultrasound exposure as well as by mechanical shear and strong laser ablation. In addition, these treatments caused wound-induced nonlytic necrotic death resulting in cell bodies we call wound-derived perikarya (WD-P). However, only cells exposed to acoustic cavitation experienced ejection of intact nuclei and nearly instant lytic necrosis. Quantitative analysis by flow cytometry indicates that wound-derived perikarya are the dominant morphology of nonviable cells, except at the strongest wounding conditions, where nuclear ejection accounts for a significant portion of cell death after ultrasound exposure. PMID- 20350694 TI - A multicenter randomized controlled evaluation of automated home monitoring and telephonic disease management in patients recently hospitalized for congestive heart failure: the SPAN-CHF II trial. AB - BACKGROUND: We performed a prospective, randomized investigation assessing the incremental effect of automated health monitoring (AHM) technology over and above that of a previously described nurse directed heart failure (HF) disease management program. The AHM system measured and transmitted body weight, blood pressure, and heart rate data as well as subjective patient self-assessments via a standard telephone line to a central server. METHODS AND RESULTS: A total of 188 consented and eligible patients were randomized between intervention and control groups in 1:1 ratio. Subjects randomized to the control arm received the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) heart failure disease management program. Subjects randomized to the intervention arm received the SPAN-CHF disease management program in conjunction with the AHM system. The primary end point was prespecified as the relative event rate of HF hospitalization between intervention and control groups at 90 days. The relative event rate of HF hospitalization for the intervention group compared with controls was 0.50 (95%CI [0.25-0.99], P = .05). CONCLUSIONS: Short-term reductions in the heart failure hospitalization rate were associated with the use of automated home monitoring equipment. Long-term benefits in this model remain to be studied. PMID- 20350695 TI - Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study. AB - BACKGROUND: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. METHODS AND RESULTS: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2 max)). Sixty patients were enrolled, and the mean follow up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2 max) were not significantly different. Death occurred more frequently with RVP. CONCLUSION: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode. PMID- 20350696 TI - Relationship between high circulating adiponectin with bone mineral density and bone metabolism in elderly males with chronic heart failure. AB - BACKGROUND: The aim of the study was to investigate the associations of adiponectin and leptin to bone mass and bone specific surrogates in elderly males with chronic heart failure (CHF). METHODS AND RESULTS: Seventy-three males (mean age 68 +/- 7 years) with stable mild to moderate CHF and 20 healthy individuals age- and body mass index-matching underwent dual energy x-ray absorptiometry measurements (bone mineral density (BMD) at hip and lumbar spine, total bone mineral content, and body composition); echocardiography; 6-minute walk test; grip strength; and biochemical assessment including adiponectin, leptin, bone specific surrogates (osteocalcin, beta-CrossLaps, osteoprotegerin [OPG], receptor activator of nuclear factor kappaB ligand [RANKL]), parathyroid hormone, 25 hydroxy vitamin D, testosterone, sex hormone-binding globulin, and NT-pro-BNP. Serum adiponectin, osteocalcin, beta-CrossLaps, OPG, RANKL, and parathyroid hormone were significantly increased in CHF patients, whereas 25-hydroxy vitamin D was significantly lower compared to healthy controls. The significant positive association was found between adiponectin level with osteocalcin, beta-CrossLaps, OPG, and RANKL among CHF patients. In multivariate regression analysis, adiponectin was a significant determinant of total hip BMD, although the variance was small (r(2) = 0.239), whereas leptin was determinant for total bone mineral content (r(2) = 0.469) in patients with CHF. CONCLUSIONS: Serum adiponectin is an independent predictor of BMD in elderly males with mild to moderate CHF, and showed a positive correlation to bone specific surrogates. Adiponectin, as cardioprotective hormone, seems to be able to exert a negative effect on bone mass in chronic heart failure. Further research is needed to confirm the potential for adipokines in the crosstalk between bone and energy metabolism in CHF patients. PMID- 20350697 TI - Serum midkine as a predictor of cardiac events in patients with chronic heart failure. AB - BACKGROUND: Midkine, a heparin-binding growth factor, has various functions such as migration of inflammatory cell and anti-apoptotic effect. Invasion of inflammatory cell and cardiomyocyte apoptosis are involved in development and progression of heart failure (HF). However, the relationship between midkine and HF has not been previously examined. Therefore, we examined clinical significance of serum midkine levels to determine the prognosis of HF patients. METHODS AND RESULTS: Serum levels of midkine were measured at admission in 216 consecutive patients hospitalized for HF and 60 control subjects. Patients were prospectively followed during a mean follow-up period of 653 +/- 375 days with the end points of cardiac death and progressive HF requiring rehospitalization. Serum concentrations of midkine were significantly higher in patients with HF than in controls. Patients with cardiac events had significantly higher concentrations of midkine than those without cardiac events. Kaplan-Meier analysis revealed that cardiac event rates increased markedly as midkine levels rose. Furthermore in the multivariate analysis, after adjustment for age, gender ,and complications, midkine was the independent predictor of cardiac events. CONCLUSION: Serum midkine levels are increased in HF patients, and midkine is a novel marker for risk stratifying HF patients. PMID- 20350699 TI - Concordant versus discordant left bundle branch block in heart failure patients: novel clinical value of an old electrocardiographic diagnosis. AB - BACKGROUND: Over the last 50 years left bundle branch block (LBBB) has been defined as homophasic (concordant: cLBBB) or heterophasic (discordant: dLBBB) when associated with a positive or negative T wave in leads I and V5-V6, respectively. LBBB is recognized as an adverse prognostic factor in heart failure (HF). The prevalence and clinical significance of cLBBB and dLBBB in HF patients are unknown. METHODS AND RESULTS: A total of 897 consecutive systolic HF patients (age 65 +/- 13 years, left ventricular ejection fraction [LVEF], 34 +/- 10%) underwent clinical characterization, electrocardiographic evaluation for LBBB diagnosis and classification, and follow-up for cardiac events (median 37 months, range 1-84). LBBB was diagnosed in 232 patients (26%), cLBBB in 71 (31%), and dLBBB in 161 (69%). The dLBBB patients were older than those with cLBBB, and presented with lower LVEF, greater left ventricular telediastolic diameter and left ventricular mass index, higher level of brain natriuretic peptide, N terminal pro-brain natriuretic peptide, renin activity, and norepinephrine (all P < .05). At Kaplan-Meier analysis, LBBB (P = .003) and dLBBB (P = .036) were associated with a worse prognosis when the composite end point of sudden death and implantable cardioverter defibrillator shock was considered. CONCLUSIONS: In systolic HF, dLBBB is associated with a worse clinical, neurohormonal, and prognostic profile. LBBB classification could represent a useful tool in routine clinical evaluation. PMID- 20350698 TI - A promoter polymorphism of the endothelial nitric oxide synthase gene is associated with reduced mRNA and protein expression in failing human myocardium. AB - BACKGROUND: Alterations of endothelial nitric oxide synthase (eNOS) enzyme activity via eNOS gene polymorphisms have been associated with significant cardiovascular morbidity and mortality. Both the thymidine to cytosine transition mutation (T(-786)-->C) in the promoter region and the missense mutation in the exon 7 coding region of the eNOS gene (G(894)-->T) have been associated with several cardiovascular disease states. We hypothesized that heart transplant recipients who carried at least 1 allele of either of the polymorphisms would have reduced myocardial tissue expression of eNOS measured in the explanted heart. METHODS AND RESULTS: Genomic DNA was isolated from myocardial tissue samples obtained from 43 explanted human hearts using standard methods. Regions of the eNOS gene were amplified from genomic DNA with a polymerase chain reaction using specific primers. Protein expression of eNOS was measured by Western blot analysis. There was a statistically significant decrease in mean eNOS expression in samples containing at least one allele for the T(-786)-->C promoter polymorphism (P=.04) compared with patients homozygous for the T allele. There was no change in eNOS expression associated with the G(894)-->T exonic polymorphisms. CONCLUSIONS: Our data show in failing human myocardium that the T( 786)-->C promoter polymorphism is associated with reduced eNOS expression, whereas the G(894)-->T polymorphism of exon 7 is not associated with change in either eNOS mRNA or protein expression. Reduced eNOS expression associated with the promoter polymorphism may contribute to the vascular, contractile, and autonomic responses to ventricular failure. PMID- 20350700 TI - Effect of left ventricular assist device placement on preexisting implantable cardioverter-defibrillator leads. AB - BACKGROUND: The left ventricular assist device (LVAD) is a therapy for patients with end-stage heart failure, many of whom have a preexisting implantable cardioverter-defibrillator (ICD). We investigated whether the implantation of a LVAD affects ICD function. METHODS AND RESULTS: Patients implanted with a LVAD between September 2000 and February 2009 were studied. Right ventricular (RV), right atrial, and left ventricular lead impedance, sensing, and capture thresholds were recorded before and after LVAD placement and subsequent lead related interventions were noted. Of the 61 patients receiving a LVAD, data were collected from 30 patients who had preexisting ICDs. Significant pre-post differences were noted for all RV lead parameters: sensing amplitude decreased from 9.2+/-3.1 to 5.7+/-3.6 millivolts (P < .001); impedance decreased from 479+/ 118 to 418+/-94 ohms (P=.008); and threshold increased from 4.3+/-6.7 to 11.0+/ 16.8 microjoules (P=.021). As a result of alterations in lead parameters, 4 patients (13%) required lead revisions and 6 patients (20%) required ICD testing. CONCLUSIONS: Differences in ICD lead function were observed after LVAD placement resulting in clinically significant interventions. These data suggest that ICD interrogation be performed post-LVAD placement and that patients be counseled for the potential need for lead revisions and ICD testing when consented for a LVAD. PMID- 20350702 TI - What are the thromboembolic risks of heart failure combined with chronic or paroxysmal AF? AB - BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. METHODS AND RESULTS: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. CONCLUSIONS: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF. PMID- 20350701 TI - The effects of race on peak oxygen consumption and survival in patients with systolic dysfunction. AB - BACKGROUND: The relationship of peak exercise oxygen consumption (VO(2)) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO(2) values and survival in HF patients with systolic dysfunction. METHODS AND RESULTS: This study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 +/- 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 +/- 12%; mean body mass index 28.7 +/- 5.4; 73% on beta-blocker). Black patients had a significantly lower peak VO(2) than white patients (14.2 +/- 5.2 versus 16.4 +/ 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO(2) was significantly associated with survival in both racial groups. CONCLUSIONS: Black HF patients had significantly lower peak VO(2), but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients. PMID- 20350703 TI - Interferon beta-1b therapy in chronic viral dilated cardiomyopathy--is there a role for specific therapy? AB - BACKGROUND: Myocardial biopsy can be used for the detection of viral genome in dilated cardiomyopathy (DCM). Pilot studies have previously reported beneficial effects on clinical outcome and safety of an antiviral therapy using interferon beta-1b in chronic viral DCM. METHODS AND RESULTS: Myocardial biopsies were taken from patients with DCM. Using polymerase chain reaction and Southern Blot analysis, viral genome could be detected in 49% of patients. In 42 patients with viral infection, off-label use with interferon beta-1b was initiated. A further 68 patients formed the control group. The outcome was evaluated after follow-up with echocardiography, exercise electrocardiogram, and New York Heart Association class. A total of 81 men and 29 women with a median left ventricular ejection fraction of 34% were included. The follow-up period was 36 months. In 33 (79%) patients with interferon beta-1b treatment, minor adverse reactions occurred, but no major adverse events were reported. No significant benefit for interferon beta 1b treatment on clinical outcome could be detected during follow-up. CONCLUSIONS: Off-label use with interferon beta-1b in patients with viral DCM is feasible and safe under routine clinical practice. Concerning the herein evaluated clinical outcome parameters, promising results from pilot studies could not be confirmed. High prevalence of parvovirus B19 (92%) might influence the results. PMID- 20350704 TI - Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. AB - BACKGROUND: Cell-based therapies offer a promising approach to reducing the short term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization. PMID- 20350705 TI - The hazards of war: blast injury headache. PMID- 20350706 TI - A novel method to quantify histochemical changes throughout the mediolateral axis of the substantia gelatinosa after spared nerve injury: characterization with TRPV1 and substance P. AB - Nerve injury dramatically increases or decreases protein expression in the spinal cord dorsal horn. Whether the spatial distribution of these changes is restricted to the central innervation territories of injured nerves or could spread to adjacent territories in the dorsal horn is not understood. To address this question, we developed a simple computer software-assisted method to precisely distinguish and efficiently quantify immunohistochemical staining patterns across the mediolateral axis of the dorsal horn 2 weeks after transection of either the tibial and common peroneal nerves (thus sparing the sural branch, spared nerve injury, [SNI]), the tibial nerve, or the common peroneal and sural nerves. Using thiamine monophosphatase (TMP) histochemistry, we determined that central terminals of the tibial, common peroneal, sural, and posterior cutaneous nerves occupy the medial 35%, medial-central 20%, central-lateral 20%, and lateral 25% of the substantia gelatinosa, respectively. We then used these calculations to show that SNI reduced the expression of SP and TRPV1 immunoreactivity within the tibial and peroneal innervation territories in the L4 dorsal horn, without changing expression in the uninjured, sural sector. We conclude that SNI-induced loss of SP and TRPV1 in central terminals of dorsal horn is restricted to injured fibers. Our new method enables direct comparison of injured and uninjured terminals in the dorsal horn so as to better understand their relative contributions to mechanisms of chronic pain. PERSPECTIVE: A simple computer software-assisted algorithm was developed to precisely distinguish and efficiently quantify immunohistochemical staining patterns across the mediolateral axis of the dorsal horn after distal sciatic-branch transection. This method will facilitate a better understanding of the relative contribution of injured and uninjured terminals to mechanisms of chronic pain. PMID- 20350707 TI - How neuroimaging studies have challenged us to rethink: is chronic pain a disease? PMID- 20350708 TI - The fundamentals of tooth movement. AB - Advances in the field of molecular phenomena have led to a fuller understanding of the mechanisms at work in tooth movement. The forces applied by orthodontic devices are converted into cellular signals via the deformation of the bony walls and the inflammatory reaction they trigger. In turn, the numerous cytokines, which are created by this process activate other messengers which differentiate, activate and inhibit the different cell populations involved in tooth movement. PMID- 20350710 TI - KommonBase for precise direct bonding of lingual orthodontic brackets. AB - On account of the morphological variations of lingual dental surfaces, indirect bonding systems have been used for bonding lingual orthodontic brackets. Improvements in bracket seating and bonding systems have enabled the development of KommonBase, a precise direct bonding system. KommonBase is characterized by a large bonding base, which can achieve a good bracket fit and precise bracket positioning while also enhancing bond strength. Furthermore, transfer trays are not required because of its self-positioning shape. KommonBase offers an advantageous alternative to conventional indirect bonding systems for the bonding of lingual orthodontic brackets. PMID- 20350712 TI - Caries risk and orthodontic treatment. AB - It is now established that orthodontic treatment increases the risk of carious lesions, with consequent harm to the patient and a high risk of compromising treatment outcome. This risk is related to the appliances, which increase the number of sites where plaque can accumulate as well as to changes in the bacterial flora and the age of the patient. A thorough evaluation of the risk of caries is therefore needed before any appliance is put in place and further evaluations should then be performed regularly throughout the course of treatment. In addition, preventive measures should be taken, involving first and foremost educating and motivating patients regarding the need for good oral hygiene. Prevention also implies adequate usage of the various sources of local fluoride administration, notably the application of fluoride-rich varnish. Other prophylactic measures such as using chlorhexidine varnish and sealing dental grooves are also recommended. Finally, the orthodontist can reduce to a minimum the use of items likely to retain dental plaque such as bands and elastomeric ties. The aim of this article is to suggest a specific diagnostic approach and to present the scientifically validated prevention measures, which need to be applied throughout orthodontic treatment. PMID- 20350715 TI - A shift of force vector from arm to brain: 3D computer technology in orthodontic treatment management. AB - For many years, we have been witnessing changes in what it takes to make a good orthodontist. A gradual shift has occurred from a manual to a technological approach, from professional intuition to image-based diagnosis and from craftsmanship to standardization of materials and procedures. Result-forecasting, reproducibility of outcomes, the transfer of, and agreement on, information and the delegation of functions, such are the future challenges our profession will have to meet. For many years already, information technology has been an indispensable partner of orthodontists to a point where we can now predict tooth movements in the occlusion and use this information in the complex mechanical manufacturing of the appliances required to achieve these displacements. Three dimensional Information Technology (3D IT) is opening up new frontiers in this domain allowing the ever-greater use of industrially-manufactured appliances while respecting the biomechanical field. It has provided end-results which are totally positive for orthodontic patients, as was already the case in implantology and prosthetics. PMID- 20350717 TI - Which method to measure dentomaxillary discrepancy? AB - Tooth-size assessment is a useful indicator of dental crowding which constitutes one of the main parameters in tooth-size arch-length discrepancy (TSALD). Systematic TSALD evaluation is imperative in all patients consulting for dentofacial orthopedic treatment. The present study aims to compare four measurement techniques for calibrating tooth size. It was performed on casts taken from 30 Moroccan patients consulting at the Dentofacial Orthopedics Department of the Rabat School of Dentistry. Four measurement methods were used to calculate the largest mesiodistal diameter of mandibular teeth mesial to the first molars. Statistical analysis showed that the methods using a digital caliper, the analog vernier caliper and the computerized technique are reliable, accurate, and interchangeable. In contrast, the analog caliper with no vernier is less accurate. PMID- 20350719 TI - [European College of Orthodontics: Commission on Membership and Tenure]. AB - A. PRETREATMENT RECORDS: 10/08/2004 (age of patient: 13 y 8 m). DIAGNOSIS: Hyperdivergent skeletal Cl. II, dental Cl. I with bimaxillary protrusion. TREATMENT: Multibracket appliance with extraction of 14/24/34/44. B. POSTTREATMENT RECORDS: 24/03/2007 (age of patient: 16 y 3 m). RETENTION: Maxillary Hawley plate and mandibular wire bonded from 33 to 44. C. POSTRETENTION RECORDS: 28/01/2009 (age of patient: 16 y 3 m). D. CLINICAL OBSERVATIONS: Consultation for an esthetic problem (bimaxillary protrusion). The extraoral examination revealed a convex, hyperdivergent profile and incompetent lip seal at rest. Endooral examination showed the presence of moderate anterior crowding, bimaxillary protrusion and Cl. I relationships. The status of the dentition and periodontium was satisfactory apart from the first permanent molars. PMID- 20350720 TI - Capillary pressure studies under low gravity conditions. AB - For the understanding of short-time adsorption phenomena and high-frequency relaxations at liquid interfaces particular experimental techniques are needed. The most suitable method for respective studies is the capillary pressure tensiometry. However, under gravity conditions there are rather strong limitations, in particular due to convections and interfacial deformations. This manuscript provides an overview of the state of the art of experimental tools developed for short-time and high-frequency investigations of liquid drops and bubbles under microgravity. Besides the brief description of instruments, the underlying theoretical basis will be presented and limits of the applied methods under ground and microgravity conditions will be discussed. The results on the role of surfactants under highly dynamic conditions will be demonstrated by some selected examples studied in two space shuttle missions on Discovery in 1998 and Columbia in 2003. PMID- 20350721 TI - A reaction time advantage for calculating beliefs over public representations signals domain specificity for 'theory of mind'. AB - In a task where participants' overt task was to track the location of an object across a sequence of events, reaction times to unpredictable probes requiring an inference about a social agent's beliefs about the location of that object were obtained. Reaction times to false belief situations were faster than responses about the (false) contents of a map showing the location of the object (Experiment 1) and about the (false) direction of an arrow signaling the location of the object (Experiment 2). These results are consistent with developmental, neuro-imaging and neuropsychological evidence that there exist domain specific mechanisms within human cognition for encoding and reasoning about mental states. Specialization of these mechanisms may arise from either core cognitive architecture or via the accumulation of expertise in the social domain. PMID- 20350722 TI - An experimental study of the stability of liquid bridges subject to shear-induced closed-flow. AB - This paper shows via experiments, the effect of closed-flows on the stability of a liquid bridge. Experiments were conducted with a 3M HFE-7500 liquid as the liquid bridge and a mixture of sodium polytungstate solution and glycerine as the outer liquid, which is encapsulated in a cylindrical cavity. Depending on the glycerine content, the Bond number ranged from 0.04 to 0.25. It was shown that a closed-flow in both the encapsulating liquid and the bridge would increase the stability of a non-cylindrical bridge depending on the direction of shear, the Bond number and the bridge volume. It was also shown that, for a given bridge volume and Bond number, there is a capillary number that gives the maximum percentage stabilization. Any further increase in the capillary number flips the direction of the bulge from top to bottom or vice versa thereby decreasing the stabilization and at some capillary number even destabilizing the bridge. The scaling of the problem was analyzed through experimental data. PMID- 20350723 TI - Interaction of oligonucleotide-based amphiphilic block copolymers with cell membrane models. AB - Oligonucleotides have unique molecular recognition properties, being involved in biological mechanisms such as cell-surface receptor recognition or gene silencing. For their use in human therapy for drug or gene delivery, the cell membrane remains a barrier, but this can be obviated by grafting a hydrophobic tail to the oligonucleotide. Here we demonstrate that two oligonucleotides, one consisting of 12 guanosine units (G(12)), and the other one consisting of five adenosine and seven guanosine (A(5)G(7)) units, when functionalized with poly(butadiene), namely PB-G(12) and PB-A(5)G(7), can be inserted into Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), which served as a cell membrane model. PB-G(12) and PB-A(5)G(7) were found to affect the DPPC monolayer even at high surface pressures. The effects from PB-G(12) were consistently stronger, particularly in reducing the elasticity of the DPPC monolayers, which may have important biological implications. Multilayers of DPPC and nucleotide based copolymers could be adsorbed onto solid supports, in the form of Y-type LB films, in which the molecular-level interaction led to lower energies in the vibrational spectra of the nucleotide-based copolymers. This successful deposition of solid films opens the way for devices to be produced which exploit the molecular recognition properties of the nucleotides. PMID- 20350724 TI - Monodisperse microspheres with poly(N-isopropylacrylamide) core and poly(2 hydroxyethyl methacrylate) shell. AB - Monodisperse core-shell microspheres, composed of poly(N-isopropylacrylamide) (PNIPAM) core with thermo-responsive swelling/shrinking function and biocompatible poly(2-hydroxyethyl methacrylate) (PHEMA) shell with "open/close" switching function, have been successfully prepared by microfluidic emulsification, free-radical polymerization and atom transfer radical polymerization (ATRP). The effects of grafting time for the ATRP and polyvinyl alcohol (PVA) concentration inside the core on the thermo-responsive behavior of core-shell microspheres are investigated. For the core-shell microspheres prepared with PVA concentration of 2% (w/v) and grafting time of 2 h, the PNIPAM core is in the shrunken state and the solid PHEMA shell protect the whole PNIPAM core at temperatures above the volume phase transition temperature (VPTT); as environmental temperature decreases below the VPTT, the PNIPAM core swells dramatically and the PHEMA shell ruptures a large area. The thermo-responsive function of the core-shell microspheres is reversible and the appearance/recovery of PHEMA shell crack exhibits an "open/close" switching function. Such core-shell microspheres are highly attractive for developing drug delivery systems with both biocompatible and thermo-responsive characteristics. PMID- 20350725 TI - Synthesis and characterization of beta-cyclodextrin-conjugated magnetic nanoparticles and their uses as solid-phase artificial chaperones in refolding of carbonic anhydrase bovine. AB - Surface-functionalized magnetic nanoparticles are widely used in various fields of biotechnology. In this study, beta-cyclodextrin-conjugated magnetic nanoparticles (CD-APES-MNPs) are synthesized and the use of CD-APES-MNPs as a solid-phase artificial chaperone to assist protein refolding in vitro is demonstrated using carbonic anhydrase bovine (CA) as model protein. CD-APES-MNPs are fabricated by grafting mono-tosyl-beta-cyclodextrin (Ts-beta-CD) onto 3 aminopropyltriethoxysilane (APES)-modified magnetic nanoparticles (APES-MNPs). Results obtained from transmission electron microscopy (TEM) and vibrating sample magnetometery (VSM) show that the synthesized magnetic nanoparticles are superparamagnetic with a mean diameter of 11.5 nm. The beta-CD grafting is confirmed by Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The amount of beta-CD grafted on the APES-MNPs is found to be 0.042 mmol g(-1) from elemental analysis. Our refolding results show that a maximum of 85% CA refolding yield can be achieved using these beta-CD-conjugated magnetic nanoparticles which is at the same level as that using liquid-phase artificial chaperone-assisted refolding. In addition, the secondary and tertiary structures of the refolded CA are the same as those of native protein under optimal conditions. These results indicate that CD-APES-MNPs are suitable and efficient stripping agents for solid-phase artificial chaperone-assisted refolding due to easier and faster separation of these nanoparticles from the refolded samples and also due to recycling of the stripping agents. PMID- 20350726 TI - Ligand-functionalised copper(II) hydroxide for quantum dot photoluminescence quenching. AB - The preparation of ligand-functionalised copper(II) hydroxide (Cu(OH)(2)) particles and their conjugation with hydrophobic CdSeS quantum dots (QDs) is reported. The photoluminescence of the QDs is efficiently quenched upon their conjugation with the functionalised Cu(OH)(2) particles. Cu(OH)(2) was functionalised with 2,2'-dipyridyl (2,2-bipy) and n-octanoic acid (OcA), by adsorption of the desired ligand to Cu(OH)(2) suspended in solvent. The resulting functionalised Cu(OH)(2) substrates were characterised using infrared, UV-visible diffuse reflectance, and X-ray photoelectron spectroscopic techniques, TEM imaging, and micro- and thermogravimetric analysis. The spectral data indicated that both 2,2-bipy and OcA coordinated to Cu(OH)(2) in a bidentate manner. The functionalised Cu(OH)(2) substrates were introduced to suspensions of hydrophobic CdSeS QDs, and the resulting QD-functionalised Cu(OH)(2) conjugates were also characterised using spectroscopic and electron microscopy techniques. UV-visible diffuse reflectance spectroscopy indicated the extension of the optical absorption of the Cu(OH)(2) to longer wavelengths upon conjugate formation. PMID- 20350727 TI - Initial orthostatic hypotension in the young is attenuated by static handgrip. AB - Initial orthostatic hypotension is common in children. Isometric handgrip increases arterial pressure, central blood volume, cardiac output, and total peripheral resistance. We show that in 14 subjects with initial orthostatic hypotension, isometric handgrip coupled with standing abolished symptoms of initial orthostatic hypotension and minimized decreases in blood pressure and cardiac output with standing. PMID- 20350728 TI - Primary ciliary dyskinesia in Amish communities. AB - Primary ciliary dyskinesia is an autosomal recessive multigenic disease that results in impaired mucociliary clearance. We have diagnosed 9 subjects with primary ciliary dyskinesia from geographically dispersed Amish communities, on the basis of clinical characteristics and ciliary ultrastructural defects. Despite consanguinity, affected individuals had evidence of genetic heterogeneity. PMID- 20350730 TI - Comparative characterization of Santolina insularis chemotypes by essential oil composition, 5S-rRNA-NTS sequencing and EcoRV RFLP-PCR. AB - Santolina insularis (Genn ex Fiori) Arrig. is a medicinal plant whose essential oil shows antiviral and antibacterial activities and potent and selective cytotoxic activity against the human colon carcinoma cell line. The occurrence of several chemotypes makes the taxonomic identification of S. insularis hard to achieve. GC-MS essential oil analyses of four chemotypes (SI1, SI2, SI3 and SI4) revealed the presence of different percentages of santolina triene, beta-pinene, myrcene, beta-phellandrene, artemisia ketone and cis-chrysanthemol, allowing a chemical discrimination. Single fragments of the 5S-rRNA-NTS region of approximately 150, 170, 260 and 280bp were produced by SI1, SI2, SI3 and SI4, respectively, and the sequence alignment of the 5S-rRNA spacer region flanked by the 3'-and 5'-ends of the coding region confirmed a consistent difference between chemotypes. Furthermore, a PCR-RFLP method was applied. From the identified sequences, an EcoRV site could be found in chemotypes SI1, SI2 and SI3 in the 5S rRNA spacer regions at 81 bp position; however, this site was absent in the chemotype SI4. This study, by showing remarkable chemical variation in the terpenoid profile and consistent genomic difference in the 5S-rRNA spacer regions, identified four chemotypes of S. insularis which could be grouped into two ecotypes, based on chemical and genomic analyses. The identification of specific gene sequences of the 5S-rRNA-NTS region and of a EcoRV site identified in this work can be used for a rapid and precise identification of the plant chemo-/ecotypes, complementing the essential oil chemical analysis. PMID- 20350731 TI - Phenotypic and genotypic characteristics of antimicrobial resistant Escherichia coli isolated from symbovine flies, cattle and sympatric insectivorous house martins from a farm in the Czech Republic (2006-2007). AB - The prevalence of antimicrobial resistant Escherichia coli was tested in symbovine flies and sympatric house martins (Delichon urbica) at a dairy farm. Antimicrobial resistant E. coli was detected in 89% (n=147) of isolates from flies within a calf barn. Isolates with the same antimicrobial resistance phenotypes, genes, and pulsotypes were found between both fly and calf E. coli isolates, suggesting that the calves were the initial source of the antimicrobial resistant strains in fly isolates. Symbovine flies were considered as important reservoirs of antimicrobial resistant E. coli strains at a dairy farm, due to their intensive contact with cattle feces and manure. House martin fecal samples from the same farm contained 4.5% (n=393) of antimicrobial resistant E. coli. House martin isolates displayed different macrorestriction profiles than fly isolates and the significance of house martins as a reservoir and vector of antimicrobial resistant E. coli appears low. PMID- 20350732 TI - Glycoconjugate histochemistry in the small and large intestine of normal and Solanum glaucophyllum-intoxicated rabbits. AB - Vitamin D participates in mineral homeostasis, immunomodulation, cell growth and differentiation. The leaves of Solanum glaucophyllum contain high levels of 1,25 dihydroxyvitamin D3 as glycoside derivatives and their chronic ingestion generates a hypervitaminosis D-like state. We analyzed changes on carbohydrate expression as a cell differentiation indicator on samples of the small and large intestine of S. glaucophyllum-intoxicated rabbits, using conventional and lectin histochemistry. Male New Zealand white rabbits were intoxicated with S. glaucophyllum during two or four weeks and killed the day after. A group of animals ("possibly recovered group") were intoxicated during 15 days and killed at day 45 of the beginning of the experiment. We found changes in the lectin binding pattern in the small and large intestine of the intoxicated rabbits. Some of these changes were reverted in the possibly recovered group. Vitamin D could be a new regulator factor of the intestinal glycosylation process. PMID- 20350733 TI - Effect of probiotic on growth performance and digestive enzyme activity of Arbor Acres broilers. AB - The effect of probiotic, Bacillus coagulans NJ0516, on growth performance and digestive enzyme activity of Arbor Acres (AA) broilers was investigated. Strains NJ0516 were added to commercial basal diets as probiotic at three final concentrations: T-1, 1x10(6) cfu g(-1); T-2, 2x10(6) cfu g(-1) and T-3, 4x10(6) cfu g(-1), respectively. Twelve groups, of 30 broilers, with three replicates for each treatment group (T-1, T-2 and T-3) and the control group treated without probiotic were used. After 49 days, broilers receiving the diets supplemented with probiotic showed significantly better growth performances including final weight and daily weight gain (DWG) than those fed the basal diet (control). As for feed conversion ratio (FCR), T-2 and T-3 showed lower value (P<0.05) than the control. However, there was no significant different in final weight, DWG and FCR between T-1, T-2 and T-3 and the survival rate was not affected (P>0.05) by the dietary treatments. The higher protease activities were observed in T-2 and T-3 (P<0.05) compared with the control and T-1. However, there was not significantly different (P>0.05) between T-2 and T-3 in protease activity. Amylase activity in T-1, T-2 and T-3 was remarkably higher (P<0.05) than that in the control. Significantly higher amylase activity was observed in T-2 compared with that of T 1. There was no remarkable difference (P>0.05) in amylase activity of T-2 compared with that of T-3, even though there was a tendency for increased activity. As for lipase activity of duodenum in broilers, assays showed no difference in all treatment groups. It showed that probiotic, B. coagulans NJ0516 administration in feed with a certain concentration displayed a growth promoting effect and increased the protease and amylase activities. PMID- 20350734 TI - Expression of Mycoplasma bovis variable surface membrane proteins in the respiratory tract of calves after experimental infection with a clonal variant of Mycoplasma bovis type strain PG45. AB - The pathomorphological findings and the expression and distribution of variable surface protein antigens (Vsp) of Mycoplasma (M.) bovis were characterised immunohistochemically in lungs of eight calves following inoculation with a Vsp A expressing clonal variant of M. bovis type strain PG45. Within 48 h post inoculation (p.i.) an innate immune response dominated by macrophages and neutrophils develops. The monoclonal antibodies (mAbs) 1A1 and 1E5 detected M. bovis Vsp antigens in paraffin tissue sections of seven calves. Vsp antigens were widely distributed and were already present at day two p.i. within macrophages and other lung compartments. Taken together, the results demonstrate that the bovine is unable to eliminate M. bovis during the time period examined. Based on the different immunohistochemical labelling patterns obtained with the mAbs, the results also support the speculation that the in vivo variability of Vsps together with immunological factors may contribute to the chronicity of pulmonary disease. PMID- 20350735 TI - Shear waves guided by the imperfect interface of two magnetoelectric materials. AB - In this paper, propagation of shear waves along a weak interface of two dissimilar magnetoelectric or magnetoelectroelastic materials is considered. Two exact dispersion relations are obtained for an imperfect electrode interface and an unelectroded interface, respectively. The existence condition of the interfacial waves is studied. Our results show that the interfacial imperfection strongly affects the velocity of the interfacial shear waves. In particular, for certain bi-magnetoelectric material, the interfacial shear waves may do not exist for a perfect interface and exist only for an imperfect interface. These findings are useful for the design of high-frequency wave devices. PMID- 20350736 TI - Broome virus, a new fusogenic Orthoreovirus species isolated from an Australian fruit bat. AB - This report describes the discovery and characterization of a new fusogenic orthoreovirus, Broome virus (BroV), isolated from a little red flying-fox (Pteropus scapulatus). The BroV genome consists of 10 dsRNA segments, each having a 3' terminal pentanucleotide sequence conserved amongst all members of the genus Orthoreovirus, and a unique 5' terminal pentanucleotide sequence. The smallest genome segment is bicistronic and encodes two small nonstructural proteins, one of which is a novel fusion associated small transmembrane (FAST) protein responsible for syncytium formation, but no cell attachment protein. The low amino acid sequence identity between BroV proteins and those of other orthoreoviruses (13-50%), combined with phylogenetic analyses of structural and nonstructural proteins provide evidence to support the classification of BroV in a new sixth species group within the genus Orthoreovirus. PMID- 20350737 TI - Plasmodesmal targeting and intercellular movement of potato mop-top pomovirus is mediated by a membrane anchored tyrosine-based motif on the lumenal side of the endoplasmic reticulum and the C-terminal transmembrane domain in the TGB3 movement protein. AB - Live-cell fluorescence microscopy was used to investigate the third triple gene block protein (TGB3) of potato mop-top pomovirus and its role in assisted targeting of TGB2 to plasmodesmata (PD). Wild-type and mutant TGB3 proteins were expressed under the control of the 35S promoter or from a virus reporter clone. Assisted targeting of TGB2 to PD was optimal when the proteins were expressed from a bicistronic plasmid in the relative ratios expected in a virus infection, suggesting that excess TGB3 inhibited PD localisation. Contrary to the generally accepted view, bimolecular fluorescence complementation showed that the TGB3 N terminus is located in the cytosol. Mutational analysis to dissect TGB3 sub domain functions showed that PD targeting was mediated by a composite signal comprising an ER-lumenal tyrosine-based motif and the C-terminal transmembrane domain. Mutation of either of these domains also abolished cell-to-cell movement of the virus. The results are discussed in the context of TGB3 membrane topology. PMID- 20350738 TI - Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2'-O methyltransferase activity in dengue virus. AB - Methyltransferases (MTases) from the genus Flavivirus encode both N-7 and 2'-O activities needed for type 1 (m(7)GpppNm) cap structure formation. We performed kinetic studies to understand the mechanisms of its progressive N-7 and 2'-O methylations. Sequential N-7 to 2'-O methylation occurred via a random bi bi and processive mechanism that does not involve enzyme-RNA dissociation. Analyses of steady state kinetic parameters showed that N-7 precedes 2'-O methylation as it turnovers RNA faster (k(cat)) resulting in 2.4-fold higher catalytic efficiency. Michaelis constants for S-adenosyl-methionine (AdoMet) in both reactions were about 10-fold lower than for their respective RNA substrates, suggesting that the rate-limiting steps in methylase reactions were associated with RNA templates. In the context of long viral RNA sequences, and compared to S-adenosyl-homocysteine, sinefungin was about 60- and 12-folds more potent against dengue N-7 and 2'-O MTase activity, exhibiting IC(50) values of 30 and 41nM, respectively. PMID- 20350739 TI - Physical and chemical properties of waste-activated sludge after microwave treatment. AB - In this study, we investigate the physical and chemical properties of waste activated sludge after treatment with microwave irradiation. The results indicate that microwave energy and contact time strongly influence the physical and chemical properties of sludge. According to the settling velocity and particle size measurements, the microwave energy of 900 W with a contact time of 60s may be the optimal condition for improving the ability of the sludge to settle. Results of the experiments have shown that supernatant turbidity, soluble chemical oxygen demand, volatile suspended solid solubilization, extracellular polymeric substances content, and inorganic nitrogen increase significantly with contact time. Based on these results, we find that the microwave irradiation treatment specified by the contact time not only improves settleability, but also disintegrates sludge and destroys microbial cells. Possible mechanisms of microwave treatment are also discussed. PMID- 20350740 TI - Hexavalent chromium removal from near natural water by copper-iron bimetallic particles. AB - The reduction of hexavalent chromium (Cr(VI)) by zero-valent iron (ZVI) is self inhibiting in near natural groundwater because insulating Fe(III)-Cr(III) (oxy)hydroxide film forms on the ZVI surface during the reaction. This study tries to overcome this deficiency by coating the surface of ZVI with copper to form copper-iron bimetallic particles. The Cr(VI) removal rate by ZVI rose significantly after the copper coating was applied. The copper loading needed for enhancing Cr(VI) removal was much higher than that needed for enhancing removal of chlorinated organic compounds or other oxidative contaminants, because of the higher oxidation potential of Cr(VI). The results of X-ray photoelectron spectroscopy (XPS) indicate that coating copper onto the surface of ZVI can not only increase the deepness of the oxidation film but also increase the oxidation state of iron in the film. This phenomenon means higher Cr(VI) removal capacity per unit weight of ZVI. PMID- 20350741 TI - The effect of antiscalant addition on calcium carbonate precipitation for a simplified synthetic brackish water reverse osmosis concentrate. AB - The primary limitations to inland brackish water reverse osmosis (RO) desalination are the cost and technical feasibility of concentrate disposal. To decrease concentrate volume, a side-stream process can be used to precipitate problematic scaling salts and remove the precipitate with a solid/liquid separation step. The treated concentrate can then be purified through a secondary reverse osmosis stage to increase overall recovery and decrease the volume of waste requiring disposal. Antiscalants are used in an RO system to prevent salt precipitation but might affect side-stream concentrate treatment. Precipitation experiments were performed on a synthetic RO concentrate with and without antiscalant; of particular interest was the precipitation of calcium carbonate. Particle size distributions, calcium precipitation, microfiltration flux, and scanning electron microscopy were used to evaluate the effects of antiscalant type, antiscalant concentration, and precipitation pH on calcium carbonate precipitation and filtration. Results show that antiscalants can decrease precipitate particle size and change the shape of the particles; smaller particles can cause an increase in microfiltration flux decline during the solid/liquid separation step. The presence of antiscalant during precipitation can also decrease the mass of precipitated calcium carbonate. PMID- 20350742 TI - Removal of polychlorinated biphenyls from aqueous solutions using beta cyclodextrin grafted multiwalled carbon nanotubes. AB - Cyclodextrins have excellent ability in the preconcentration of organic pollutants from aqueous solutions by forming inclusion complexes. Multiwalled carbon nanotubes (MWCNTs) possess high adsorption capacity in the removal of organic pollutants through the formation of conjugated complexes. In this paper, beta-cyclodextrin (beta-CD) was grafted on the surfaces of MWCNTs by using plasma technique. The beta-CD grafted MWCNTs (MWCNT-g-CD) were characterized by using Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, thermo gravimetric analysis-differential thermal analysis, and scanning electron microscopy in detail. The prepared MWCNT-g-CD were used to remove polychlorinated biphenyls (PCBs) from aqueous solutions under ambient conditions. The results suggest that MWCNT-g-CD have much higher adsorption capacity than MWCNTs in the removal of PCBs from aqueous solutions. MWCNT-g-CD are suitable materials in the preconcentration and immobilization of PCBs from large volumes of aqueous solutions in environmental pollution cleanup. PMID- 20350743 TI - The relative influence of diet and serum concentrations of organochlorine compounds on K-ras mutations in exocrine pancreatic cancer. AB - BACKGROUND: In exocrine pancreatic cancer (EPC) mechanistic relationships may exist among some organochlorine compounds (OCs) and mutations in the K-ras oncogene, as well as among the latter and dietary factors. OBJECTIVE: To analyze (1) the relationship between food intake and serum concentrations of OCs in EPC patients and (2) the relative influence of food and OCs on the frequency of K-ras mutations in EPC. PATIENTS AND METHODS: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission (N=135 patients with data on OCs and diet, and N=97 with additional information on K-ras status). OCs were measured by high-resolution gas chromatography with electron capture detection. RESULTS: Consumption of milk and other dairy products was positively associated with concentrations of p,p'-DDT, PCB 138 and PCB 153 (log transformed betas=0.652, 0.588 and 0.317, respectively; all p<0.05). When adjusted by OCs, dairy products were no longer associated with K-ras. By contrast, after adjusting by consumption of dairy products, patients with the highest concentrations of p,p'-DDT and some PCBs remained more likely to have a K ras-mutated EPC than patients with lower concentrations (OR for upper tertile of PCB 138=5.5, 95% CI: 1.3-23.4). CONCLUSIONS: Dairy products were a source of OCs. The association between dairy products and K-ras mutations was not independent of OCs. By contrast, the association between OCs and K-ras was not confounded by dairy products. OCs may be more likely to contribute to the occurrence of K-ras mutations than nutrients contained in dairy products. PMID- 20350744 TI - Greywater reuse for irrigation: effect on soil properties. AB - A controlled study of the effect of greywater (GW) irrigation on soil properties was conducted. Containers of sand, loam and loess soils were planted with lettuce, and irrigated with fresh water, raw artificial GW or treated artificial GW. Greywater was treated using a recirculating vertical-flow constructed wetland. Soil samples were collected every 10 days for the 40-day duration of the study, and plant growth was measured. Soils were analysed for physicochemical and biological parameters to determine changes caused by the different treatments. It was demonstrated that raw artificial GW significantly increased the development of hydrophobicity in the sand and loam soils, as determined by water droplet penetration time. No significant changes were observed for the loess soil under all treatments. Observed hydrophobicity was correlated with increased oil and grease and surfactant concentrations in the soil. Zeta (zeta) potential of the soils was measured to determine changes in the soil particle surface properties as a result of GW irrigation. A significant change in zeta-potential (less negative) was observed in the raw artificial GW-irrigated sand, whereas no difference was observed in the loam or loess. Soils irrigated with fresh water or treated GW exhibited no increase in hydrophobicity. Fecal coliform bacteria were absent or <10 CFU g(-1) in soils irrigated with fresh water or treated GW, but at least 1 order of magnitude higher in raw artificial GW irrigated soils. Only in the last sampling event and only for the loess soil was plant growth significantly higher for fresh water irrigated vs. raw or treated GW irrigated soils. This study demonstrates that treated GW can be effectively irrigated without detrimental effects on soil or plant growth; however, raw GW may significantly change soil properties that can impact the movement of water in soil and the transport of contaminants in the vadose zone. PMID- 20350745 TI - Prospective randomized evaluation of FOOT gel pads for operating room staff COMFORT during laparoscopic renal surgery. AB - OBJECTIVES: We evaluated the comfort level of our laparoscopy team during and after laparoscopic renal surgery, with or without the use of gel footpads. METHODS: Between September 2008 and April 2009 we prospectively randomized 100 consecutive laparoscopic renal procedures to examine whether the use of a foot gel pad altered the surgical team's comfort level. A questionnaire was used to measure the discomfort in 18 different subjects before and during surgery, and one day postoperatively. The procedures performed with or without the foot gel pads were compared. RESULTS: One hundred laparoscopic procedures were randomized to being performed with and without gel pads. In 50 procedures, the foot gel pad was used. The mean age of the subjects was 36 years (range 25-52). The mean surgical experience was 7 years. The characteristics of the participants in procedures with and without the gel pad were similar. In the immediate postoperative period, there were significantly more breaks taken (P = .001), number of stretches (P = .001), foot pain (P = .003), knee pain (P = .001), back discomfort (P = .001), overall discomfort (P = .001), and diminished level of energy (P = .049) in the group not using the gel pad. Of the 24-hour postoperative time point, evaluation significantly favored the gel pads regarding foot pain (P = .004), overall amount of discomfort (P = .001), and energy level of the participants (P = .044). CONCLUSIONS: The use of foot gel pads improves surgeon comfort and ergonomics during laparoscopy. The pads have been incorporated into our routine operating room set-up and may improve surgical performance by diminishing fatigue and discomfort. PMID- 20350746 TI - Influence of IGFBP3 gene polymorphisms on IGFBP3 serum levels and the risk of prostate cancer in low-risk Korean men. AB - OBJECTIVES: To understand the relationship between the -202 A/C single-nucleotide polymorphism (SNP) of the insulin-like growth factor-binding protein 3 (IGFBP3) gene, IGFBP3 serum levels, and risk of prostate cancer (PCa) in a Korean population, as a potential reason for the lower incidence of PCa in the Korean population. METHODS: The IGFBP3 levels were measured and the -202 A/C SNP of the IGFBP3 gene was typed for 225 PCa cases and the same number of matched controls. Linear regression analysis and unconditional logistic regression analysis were used to test for the associations between the genotypes and the circulating IGFBP3 levels and the risk of PCa, respectively. To adjust for the potential bias introduced by the hospital cohort, the result of the genotyping was compared with that of 683 community-indwelling healthy men. RESULTS: Significantly lower plasma levels of IGFBP3 were noted in the PCa cases. Lower IGFBP3 plasma levels were associated with an increased number of C alleles (P<.001). Compared with the PCa cases, a lower frequency of the C allele was found in the hospital and community controls (P<.05). Compared with AA genotype, logistic regression analysis revealed an increased risk of PCa in subjects who were CC genotype (odds ratio: 2.39, 95% confidence interval: 1.05-5.48). Larger odds (odds ratio: 3.37, 95% confidence interval: 1.35-8.43) for PCa were associated with CC genotype when the analysis was confined to those who had high-risk PCa. CONCLUSIONS: The results supported the protective role of -202 A/C SNP of the IGFBP3 gene against PCa in Korean men. PMID- 20350747 TI - The urologist's role in the management of spina bifida: a continuum of care. AB - Caring for the child with spina bifida necessitates lifelong care by a coordinated team of health care providers, and the urologist plays a vital role in this team. The most important management goal of the urologist is the early establishment and consistent maintenance of a lower pressure urinary reservoir. Ensuring social continence along with its attendant social independence provides some of the greatest management challenges. In those patients who fail medical therapy, surgeons, caregivers, and patients must understand the scope of lower urinary tract reconstruction, the need for strict compliance, and the possibility of future surgery. In this article, we review the recent advances in spina bifida management. PMID- 20350748 TI - Tuberculous orchiepididymitis during 1978-2003 period: review of 34 cases and role of 16S rRNA amplification. AB - Genitourinary tuberculosis was diagnosed in 543 patients in Spanish hospital from 1978 through 2003. Of the 371 male 34 (9.2%) had orchiepididymitis. Mean age was 52.7 years and the presenting symptom was scrotal swelling and/or pain. Over 50% of cases involved the right ovotestis. Associated renal tuberculosis and active disease in extraurological organs presented in 64% and 19.2% of cases, respectively. Diagnosis was established by culture of Mycobacterium tuberculosis recovery from urine and/or purulent scrotal exudate. Genomic amplification techniques aided the diagnosis in 8 patients. Treatment was rifampin, isoniazide, and pyrazinamide or ethambutol. Eight patients required combined medical and surgical treatment. PMID- 20350749 TI - Long-term survival after radical prostatectomy for men with high Gleason sum in pathologic specimen. AB - OBJECTIVES: To evaluate the long-term outcomes of patients with high Gleason sum 8-10 at radical prostatectomy (RP) and to identify the predictors of prostate cancer-specific survival (CSS) in this cohort. METHODS: The institutional RP database was queried. A total of 9381 patients with complete follow-up underwent RP from 1982 to 2008. Of these 9381 patients, 1061 had pathologic Gleason sum 8 10 cancer. The patient and prostate cancer characteristics were evaluated. Survival analyses were performed using the Kaplan-Meier method. Univariate and multivariate proportional hazard regression models were created to evaluate the pertinent predictors of CSS (death from, or attributed to, prostate cancer). RESULTS: The median preoperative prostate-specific antigen level was 7.6 ng/mL; 435 men had clinical Stage T1 tumor, 568 had Stage T2, and 36 had Stage T3. The biopsy Gleason sum was <7, 7, and >7 in 244 (22.3%), 406 (37.2%), and 425 (38.9%) patients, respectively. The median follow-up was 5 years (range 1-23). The actuarial 15-year recurrence-free survival, CSS, and overall survival rate was 20.7%, 57.4%, and 45.4%, respectively. On multivariate analysis, the predictors of poor CSS were pathologic Gleason sum 9-10 and seminal vesicle and lymph node involvement. Patients with pathologic Gleason sum 8 and organ-confined disease had a CSS rate of 89.9% at 15 years. CONCLUSIONS: The results of our study have shown that 80% of the men with Gleason sum 8-10 who undergo RP will have experienced biochemical recurrence by 15 years. However, the CSS rate approached 90% for men with pathologic organ-confined disease. Higher pathologic Gleason sum 9-10 and seminal vesicle and lymph node involvement were independent predictors of worse CSS. PMID- 20350751 TI - SIU scholar: Dr. Egi Edward Manuputty. PMID- 20350750 TI - The effect of intramuscular testosterone enanthate treatment on stretched penile length in prepubertal boys with hypospadias. AB - OBJECTIVES: To define the responses of stretched penile length (PL) to intramuscular testosterone enanthate (TE) treatment in prepubertal boys with hypospadias. METHODS: We examined 17 Japanese boys with hypospadias at 1.4 +/- 1.3 (mean +/- SD) years of age. Their PLs were 2.79 +/- 0.37 cm and -1.16 +/- 0.88 SD of the mean. The etiology of hypospadias included sex chromosome disorders of sex development in 5, mastermind-like domain-containing 1 deficiency in 1, and unknown cause in the others. No mutation was identified in the SRD5A2 or AR gene. All the boys received as many as three intramuscular injections of TE 25 mg every 4 weeks (one injection in 3 boys, two in 5, and three in 9). RESULTS: The TE treatment significantly increased PL by 1.01 +/- 0.50 cm and 2.27 +/- 0.99 SD (cm, P = .0002; SD, P = .0002). Age, body surface area (BSA), and PL before the treatment did not significantly correlate with the effect of TE treatment on PL. The effect of TE treatment on PL at the first injection in Japanese boys with hypospadias (0.35 +/- 0.20 cm and 0.91 +/- 0.62 SD) was significantly less than that in micropenis at 2.6 +/- 3.1 years of age (0.64 +/- 0.26 cm and 1.37 +/- 0.68 SD) (cm, P = .0008; SD, P = .02). CONCLUSIONS: These data indicate that (1) the intramuscular TE treatment significantly increases PL for hypospadias in prepubertal boys, with no demonstrable SRD5A2 or AR mutation; (2) age, BSA, and PL before the treatment are not significantly contributing factors to the effect of TE treatment; and (3) the effect of TE treatment for hypospadias is significantly less than that for micropenis. PMID- 20350752 TI - The value of histologic subtyping on outcomes of clear cell and papillary renal cell carcinomas: a meta-analysis. AB - OBJECTIVES: To investigate the survival differences among clear cell renal cell carcinoma (RCC) and type 1 and type 2 papillary RCCs by means of a meta-analysis. METHODS: We combined data from studies published between 1997 and 2009. The effect sizes of overall survival were estimated by unadjusted or adjusted hazard ratio. Survival rates between clear cell RCC and nonclear cell RCC were compared by uni- and multivariate analyses of 3 studies including 2169 and 2455 patients, respectively. Survival outcomes between clear cell RCC and papillary RCC were compared by uni- and multivariate analyses of 17 studies involving 21,856 patients and 3 studies involving 3112 patients, respectively. Survival rates between type 1 and type 2 papillary RCCs were compared by uni- and multivariate analyses of 8 studies involving 634 patients and 5 studies involving 438 patients, respectively. RESULTS: Patients with clear cell RCC had poorer survival than patients with nonclear cell type in univariate analysis (hazard ratio, 2.02; P < .001). The overall survival of patients with clear cell RCC was not different from that of patients with papillary RCC in uni- and multivariate analyses. Patients with type 2 papillary RCC had a poorer outcome than patients with type 1 papillary RCC in uni- and multivariate analyses (hazard ratios, 2.91 and 1.80; P < .001 and P = .044, respectively). CONCLUSIONS: Meta-analysis confirms that clear cell RCC and papillary RCC are not different in survival outcomes. In addition, type 2 papillary RCC shows poorer survival than type 1 papillary RCC. PMID- 20350753 TI - Experience with robot assisted laparoscopic surgery for upper and lower benign and malignant ureteral pathologies. AB - OBJECTIVES: To present our experience and outcomes of robot-assisted laparoscopic surgery (RALS) performed for different ureteral pathologies and to discuss the true utility of robotics in ureteral surgery. METHODS: We reviewed a total of 44 procedures performed for diverse ureteral pathologies involving the proximal and distal ureter in 2 institutions from July 2006 to July 2009. Operative time, blood loss, length of stay, complications, and subjective and objective follow-up were evaluated. RESULTS: The 44 cases included 18 distal ureteral procedures including 5 distal ureterectomy with ureteroneocystostomy; 1 ureteroneocystostomy with psoas hitch; 2 ureteroneocystostomy with vesicovaginal fistula repair; 9 megaureter repairs in 8 cases; there were 12 proximal ureteral procedures including 7 ureteroureterostomies and 4 retrocaval ureter repairs; 10 ablative procedures consisting of 5 nephroureterectomies with cuff of bladder and 5 nephroureterectomies and 4 miscellaneous procedures. The mean operative time was 137.9 minutes (range: 70-240). Mean blood loss was 98.2 mL (range: <50-400). There were no urine leaks. Mean drain tube duration was 1.4 days (range: 1-2.5) and mean hospital stay was 2.4 days (range: 1-6). Complications included 1 case of sepsis and 1 antibiotic-induced infection. Average follow-up period was 13.5 months. Operative success as defined by symptom resolution and imaging was 100%. CONCLUSIONS: RALS is feasible, safe, and an effective option for ureteral pathologies at any level of the ureter with minimal peri-operative morbidity. However, appropriate port placement, patient positioning, and versatile experience of team is critical in handling such cases for better outcomes. PMID- 20350754 TI - Intraoperative floppy iris syndrome: facts for the urologist. AB - Intraoperative floppy iris syndrome (IFIS) consists of a triad of flaccid and billowing iris, iris prolapse through the surgical incisions, and progressive pupil constriction. IFIS increases the risk for complications during cataract surgery. It was first described in patients on tamsulosin treatment but can also be seen in patients on other non-subtype specific alpha(1)-adrenergic receptor (alpha(1)AR) antagonists. Urologists who are initiating treatment with alpha(1)AR antagonists should inform their patients that these drugs may increase the difficulty of cataract surgery, but once the ophthalmologists are forewarned, necessary safety measures can be taken to achieve good surgical results. PMID- 20350755 TI - Robot assisted laparoscopic pelvic lymphadenectomy at the time of radical cystectomy rivals that of open surgery: single institution report. AB - OBJECTIVE: The purpose of this study was to analyze the pelvic lymph node dissection (PLND) and margin status using a standard technique in the first 35 patients undergoing robot-assisted radical cystectomy (RARC) at our institution while establishing a robotics program, and then to compare the results to the past 35 open radical cystectomy (ORC) performed at our institution. MATERIALS AND METHODS: After obtaining institutional review board approval, we reviewed the clinical and pathologic data from 70 consecutive patients with clinically localized bladder cancer who underwent radical cystectomy with PLND from April 2007 to June 2009. Thirty-five operations were performed open and 35 used the da Vinci robotic system. The PLND was performed in all patients using the same template. RESULTS: There was no significant difference between the ORC and RARC group in regards to patient characteristics, tumor stage (43% ORC and 40% RARC having pT3/pT4 disease), and node status (29% N+ in each group). The median total lymph node yield was similar, with 15 (interquartile range [IQR] 11, 22) in the ORC group and 16 (IQR 11, 24) in the RARC group (P = 0.5). One patient who underwent RARC had a positive margin compared with 3 patients in the ORC group. CONCLUSIONS: The initial 35 RARC with PLND performed at our institution compared with the last 35 ORC resulted in equivalent lymph node yield and similar rates of positive margins. RARC with PLND is feasible, safe, and effective when performed at a high-volume center by an experienced team. PMID- 20350757 TI - Spider-man, magnets, and urethral-cutaneous fistula. AB - Self-inserted foreign bodies in the genitourinary tract or externally attached to the male genitalia can be challenging to the urologist. These cases often necessitate urgent assessment and intervention. We present the case of a 12-year old boy who inserted 1 magnet into his urethra and placed a second on the ventral surface of the penis. This led to the development of a urethral-cutaneous fistula. To our knowledge, this is the first reported case illustrating the development of an iatrogenic fistula after self-insertion of a foreign body in the genitourinary tract. PMID- 20350756 TI - Metabolic evaluation in stone disease metabolic differences between the pediatric and adult patients with stone disease. AB - OBJECTIVE: To determine the metabolic risk factors in children and adults with stone disease and any differences between the metabolic risk factors of children and adult patients with stone disease. METHODS: Between 1999 and 2007, 285 adults with recurrent stone disease and 71 children with primary or recurrent urinary stone disease underwent metabolic evaluation in our clinic. The evaluation included blood chemistry studies and 24-hour urine collection in the pediatric and adult groups. RESULTS: The mean age of the children was 9.35 years (range: 1 14) and 42.1 years (range: 14-71) in the adult patients. Metabolic risk factors were demonstrated in 90.53% (n = 258) of the adult and 88.73% (n = 63) of the pediatric patients. Although hypercalciuria (50.5%, n = 144) was the most common metabolic risk factor in the adult group, hypocitraturia was the most common metabolic risk factor in the pediatric group (57.74%, n = 41). Furthermore, in the adult group, 136 patients had more than 1 risk factor, and in the pediatric group, 24 patients had more than 1 risk factor. CONCLUSION: Although hypocitraturia is the most common risk factor in pediatric urolithiasis patients and hypercalciuria is the most common risk factor in adult patients, all patients with stone formation should be given a limited metabolic evaluation because such patients may also have a metabolic abnormality. PMID- 20350758 TI - Characterization and management of voiding dysfunction in children with attention deficit hyperactivity disorder. AB - OBJECTIVES: To investigate whether voiding dysfunction (VD) in children with attention deficit hyperactivity disorder (ADHD) could be treated successfully using individualized therapy. We also sought to describe the spectrum of voiding symptoms experienced by children with ADHD. ADHD is diagnosed in 3-5% of children. These children have a greater incidence of VD than non-ADHD controls, and it is less amenable to treatment. METHODS: A comprehensive history assessed the nature of the voiding disorder. A physical examination, screening urologic ultrasonography, and urinalysis were routinely performed, with electromyography combined with uroflowmetry performed for certain cases. Treatment was individualized to include behavioral modification, bowel and diet management, biofeedback, pharmacotherapy, and close follow-up. RESULTS: A total of 75 children with ADHD were referred because of VD. The 75 children (39 boys and 36 girls) were 5-16 years old. Of the 75 children, 60 were taking medication for ADHD. All the children had daytime wetting (>1/d, 5-7 d/wk) and urgency. In addition, 88% had frequency and 87% had sleep enuresis. Of the 75 families, 56 proceeded with our prescribed program. Of the 56 children, 47 (83.9%) had complete resolution or improvement of the daytime symptoms. Of the 17 patients (30.4%) with complete resolution, 9 responded to behavior modification and anticholinergics and 8 needed biofeedback. Of the 30 patients with a partial response (53.6%), 9 responded to behavior modification alone, 15 to behavior modification and anticholinergics, and 6 required all 3 modalities. Of the 56 children, 9 failed to respond to any of the 3 modalities. CONCLUSIONS: Diurnal symptoms constituted the most common referred complaint in children with ADHD. VD can be successfully treated if the treatment is individualized. Multimodal treatment, including behavior modification combined with anticholinergic agents and/or biofeedback, appears to be effective in managing VD in most of these challenging cases. PMID- 20350759 TI - Hydronephrosis caused by ureterosciatic herniation. AB - A 69-year-old woman with history of operation for stress urinary incontinence presented with left flank soreness. Physical examination revealed knocking tenderness at left costal-vertebral angle. Her serum creatinine level was 1.2 mg/dL and urine analysis was negative. Ultrasonography showed left hydronephrosis, and computed tomography scan revealed ureterosciatic herniation. An antegrade placement of the indwelling ureteral stent was performed. After 3 months, the double J catheter was removed and the patient recovered without recurrent symptoms. PMID- 20350760 TI - False penile fracture: value of different diagnostic approaches and long-term outcome of conservative and surgical management. AB - OBJECTIVES: We determined the value of clinical and radiological findings in diagnosis of false penile fracture. Also, the long-term outcome of conservative and surgical treatment of such patients was evaluated. METHODS: Seventeen patients with false penile fracture were treated conservatively (3 patients) and surgically (14 patients) at our center. Medical records were retrospectively reviewed for etiology, symptoms, signs of physical examination, and information on findings of surgical exploration. Data on erectile function and penile sequelae were obtained during follow-up using the Sexual Health Inventory for Men (SHIM) questionnaire and local examination. RESULTS: The most common cause of false penile fracture is sexual intercourse (76.5%). False fracture was suspected in 3 patients who presented with small hematoma and slow post-trauma detumescence; intact tunicas were diagnosed by magnetic resonance imaging (MRI) in all of them and were managed conservatively. Surgical penile exploration was performed in 14 cases, in whom preoperative ultrasound was done in 6, and it was false positive for presence of tunical tear in 50%. Exploration revealed nonspecific dartos bleeding in 9 cases and avulsed superficial dorsal vein in 5. Long-term follow-up (mean=93 months) was available for 16 patients, among whom there was no complications. CONCLUSIONS: In most cases, false penile fracture is indistinguishable from true penile fracture either clinically or radiologically. In atypical cases, MRI seems to be a promising modality for diagnosis of such patients. The long-term outcome of conservative and surgical treatment is excellent. PMID- 20350761 TI - Successful percutaneous transperineal drainage of a large prostatic abscess. AB - We present a case of an 83-year-old man with septic shock secondary to an extremely large prostatic abscess. Antibiotics and transperineal percutaneous drainage with a suprapubic-type Malecot catheter successfully treated the abscess. Follow-up images reveal resolution of the abscess. Broad-spectrum antibiotics and drainage permitted a full recovery. PMID- 20350762 TI - Development and validation of an abbreviated version of the expanded prostate cancer index composite instrument for measuring health-related quality of life among prostate cancer survivors. AB - OBJECTIVES: Widespread implementation of health-related quality-of-life (HRQOL) measurement in prostate cancer practice and research requires concise instruments. With 50 questions, the full-length Expanded Prostate Cancer Index Composite (EPIC) is cumbersome to administer outside of studies focusing exclusively on HRQOL. To facilitate HRQOL measurement in a broad range of prostate cancer research and practice settings, we developed and validated an abbreviated version of the EPIC. METHODS: The 50 questions that constitute the full-length EPIC-50 were evaluated to identify the items suitable for elimination while retaining the ability to measure the 5 prostate cancer-specific HRQOL domains of the EPIC-50. The resulting abbreviated version (EPIC-26) was validated using question responses from 252 subjects who had undergone brachytherapy, external beam radiotherapy, or prostatectomy for prostate cancer. The EPIC-26 internal consistency was measured by Cronbach's alpha coefficient and reliability using test-retest correlation. RESULTS: Using the high item-scale correlations, clinically relevant content, and preservation of domain psychometrics, 26 items were retained in the EPIC-26 from the 50 questions in the full-length EPIC-50. A high correlation was observed between the EPIC-50 and EPIC-26 versions for the urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal domain scores (all r >= 0.96). The correlations between the different domains were low, confirming that EPIC-26 retained the ability to discern the 5 distinct HRQOL domains. The internal consistency and test-retest reliability for EPIC-26 (Cronbach's alpha >= 0.70 and r >= 0.69, respectively for all 5 HRQOL domains) supported its validity. CONCLUSIONS: EPIC-26 is a brief, valid, and reliable subjective measure of health quality among patients with prostate cancer and is suitable for measuring the HRQOL among patients undergoing treatment of early-stage prostate cancer. PMID- 20350763 TI - Laparoscopic management for fibroepithelial polyp causing ureteropelvic junction obstruction in a child. AB - An 11-year-old boy with episodes of intermittent gross hematuria and recurrent left flank pain was referred to our institute with left ureteropelvic junction (UPJ) obstruction. (99m)Tc diethylenetriamine pentaacetic acid (DTPA) renography revealed an obstructive pattern in the left kidney, and the existence of a crossing vessel at the UPJ was suspected with excretory urography. Laparoscopic surgery was performed, and intraoperatively no aberrant vessels were found. Upon opening the ureter, a solitary round polyp was found. The segment of the UPJ area containing the polyp was completely removed, followed by laparoscopic dismembered pyeloplasty. Pathologic findings demonstrated a benign fibroepithelial polyp. PMID- 20350764 TI - Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy. AB - OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that induces tolerance to host immune surveillance within the tumor microenvironment. The present study aimed to investigate IDO expression and its prognostic significance in invasive cervical cancer. METHODS: Immunohistochemical expression of IDO in tumor tissues and its association with clinicopathological factors and survival were analyzed in 112 stage IB-IIB cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy. RESULTS: IDO was diffusely expressed in tumor cells in 29 (26%) cases and focally expressed at the invasive front in 29 (26%) cases, while the other 54 (48%) cases were IDO negative. IDO expression was positively correlated with clinical stage, lymph node metastasis, and lymph-vascular space invasion, but not with histological type. Patients with diffuse IDO expression had significantly reduced overall survival (OS) and disease-free survival (DFS) compared to patients with no IDO expression. The 5-year OS/DFS rates for the IDO-negative, focally positive, and diffusely positive groups were 92.3%/84.9%, 89.5%/75.8%, and 65.5%/51.7%, respectively. When we analyzed patients with stage IB disease alone (n=67), the OS and DFS for the IDO-diffusely positive group were significantly lower than those for the IDO-negative group. In multivariate analysis, diffuse IDO expression was found to be an independent prognostic factor for impaired OS and DFS. CONCLUSIONS: Diffuse expression of IDO in the tumor obtained from Stage IB IIB cervical cancer patients who underwent radical hysterectomy was correlated with an unfavorable clinical outcome. These findings suggest that IDO may be a novel post-operative prognostic indicator for stage IB-IIB cervical cancer. PMID- 20350765 TI - Nonvolatile buffer coating of titanium to prevent its biological aging and for drug delivery. AB - The osseointegration capability of titanium decreases over time. This phenomenon, defined as biological aging of titanium, is associated with the disappearance of hydrophilicity and the progressive accumulation of hydrocarbons on titanium surfaces. The objective of this study was to examine whether coating of titanium surfaces with 4-(2-Hydroxylethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, a nonvolatile zwitterionic chemical buffering agent, could prevent the time dependent degradation of the bioactivity of titanium. Commercially pure titanium samples, prepared as disks and cylinders, were acid-etched with H(2)SO(4). A third of the samples were used for experiments immediately after processing (new surfaces), while another third were stored under dark ambient conditions for 3 months (3-month-old surfaces). The remaining third were coated with HEPES after acid-etching and were stored for 3 months (HEPES-coated 3-month-old surfaces). The 3-month-old surfaces were hydrophobic, while new and HEPES-coated 3-month-old surfaces were superhydrophilic. Protein adsorption and the number of osteoblasts attached during an initial culture period were substantially lower for 3-month old surfaces than for new and HEPES-coated 3-month-old surfaces. Alkaline phosphatase activity and calcium deposition in osteoblast cultures were reduced by more than 50% on 3-month-old surfaces compared to new surfaces, whereas such degradation was not found on HEPES-coated 3-month-old surfaces. The strength of in vivo bone-implant integration for 3-month-old implants, evaluated by the push in test, was 60% lower than that for new implants. The push-in value of HEPES coated 3-month-old implants was equivalent to that of new implants. Coating titanium surfaces with HEPES containing an antioxidant amino acid derivative, N acetyl cysteine (NAC), further enhanced osteoblast attachment to the surfaces, along with the increase level of intracellular glutathione reserves as a result of cellular uptake of NAC. These results suggest that HEPES coating of titanium surfaces maintained their superhydrophilicity for at least 3 months and resulted in a continuous retention of bioactivity and osteoconductivity similar to freshly prepared surfaces. This coating technology may be useful for preventing biological aging of titanium and delivering biological molecules for synergistic enhancement of bone-titanium integration. PMID- 20350766 TI - The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice. AB - Pharmacokinetics and therapeutic efficacy of submicron/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially implanted in BALB/c mice and the coronal brain sections were analyzed for bio-distribution of paclitaxel on 14, 28 and 42 days post-implantation. BALB/c nude mice with intracranial human glioblastoma (U87 MG-luc2) were used in the therapeutic efficacy study. Animals were randomized to intracranial implantation of F3 and H80 with paclitaxel dose of 10mg/kg, placebo F3, placebo H80, weekly intratumoral injection of Taxol (10mg/kg) or no treatment and the treatment response was analyzed by bioluminescence imaging and histological (H&E, Ki-67) examinations. Enhanced, therapeutic paclitaxel penetration (approximately 1 microm) in the mouse brain up to 5mm from the implant site even after 42 days post-implantation from F3 and H80 was confirmed and deduced to be diffusion/elimination controlled. F3 and H80 demonstrated significant (approximately 30 fold) tumor inhibition and significantly low tumor proliferation index after 41 days of treatment in comparison to sham and placebo controls. The submicron/nanoscale implants are able to demonstrate optimal paclitaxel pharmacokinetics in the brain/tumor with significant tumor inhibition in a glioblastoma xenograft model in mice and hence could be potentially useful to treat highly recurrent GBM. PMID- 20350767 TI - Effect of treatment on serum glial cell line-derived neurotrophic factor in bipolar patients. AB - OBJECTIVE: Post-mortem studies have demonstrated various glial deficits in different brain areas of patients diagnosed with bipolar disorder (BD). Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor beta family which has been implicated in the pathophysiology of BD. This study aimed to determine whether GDNF in serum was abnormal in BD, and how it responded to drug treatment of BD. METHOD: Serum GDNF concentrations were measured in BD patients before treatment, after 8 weeks of drug treatment, and in control subjects using a sandwich ELISA method. RESULTS: Before treatment, serum GDNF was significantly lower in BD patients during both manic (P<0.001) and depressive (P<0.001) episodes than in control subjects. From baseline to remission after 8 weeks of treatment, the increase in serum GDNF was statistically significant (P<0.001). CONCLUSIONS: The present study suggests that lower GDNF levels might be involved in the pathophysiology of BD and drug treatment increases the GDNF in BD. PMID- 20350768 TI - Nigral neurodegeneration triggered by striatal AdIL-1 administration can be exacerbated by systemic IL-1 expression. AB - Neuroinflammation has been proposed as an important component of Parkinson's Disease (PD) aetiology and/or progression. However, the inflammatory components and the mechanisms underlying their effects are only partially known. By injecting an adenovirus expressing IL-1 in the striatum, we provoked progressive neurodegeneration of dopaminergic cells in the substantia nigra, motor symptoms and microglial activation. All these effects were attenuated by an anti inflammatory treatment. Interestingly, peripheral inflammatory stimuli exacerbated IL-1beta induced neurodegeneration and the central inflammatory reaction. These data provide evidence that central, chronic IL-1beta expression can trigger and systemic IL-1beta exacerbate nigral neurodegeneration and highlight the functional relevance of this cytokine in PD. PMID- 20350769 TI - Long-term changes in serum cholesterol level does not influence the progression of coronary calcification. AB - BACKGROUND: A number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC. METHODS: The study population comprised 510 patients with stable angina pectoris, mean age of 63 +/- 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up. RESULTS: CL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p=0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 +/- 63 from baseline in the 1st (upper) quartile, and by 350 +/- 44, 403 +/- 41 and 480 +/- 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p=0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes. CONCLUSIONS: Longitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC. PMID- 20350770 TI - Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation. AB - BACKGROUND: This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). METHODS: 57 patients (22 men, 81 +/- 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 +/- 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve(r) aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIENTM prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. RESULTS: There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade >= 3 (5055 +/- 1753, n = 3) than in patients with AR grade < 3 (1723 +/- 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). CONCLUSION: Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures. PMID- 20350771 TI - Direct detection and genotyping of Toxoplasma gondii in meat samples using magnetic capture and PCR. AB - Different transmission routes, including the ingestion of undercooked meat, can result in Toxoplasma gondii infection in humans. The development of effective prevention strategies is hampered by a lack of quantitative information on the contamination level of different types of meat. Therefore, we developed a method for detection and quantification of T. gondii. The method involved preparation of crude DNA extract from hundred gram samples of meat, magnetic capture of T. gondii DNA and, quantitative real-time PCR targeting the T. gondii 529-bp repeat element. The detection limit of this assay was approximately 230 tachyzoites per 100 g of meat sample. There was a linear relation between the number of parasites added to the samples and Cp-values. Results obtained with the PCR method were comparable to bioassay results for experimentally infected pigs, and to serological findings for sheep. In addition, the T. gondii in 50% of the positive sheep samples could be genotyped by sequencing of the GRA6 gene, after isolation of the gene by magnetic capture. Two subtypes of GRA6 type II were identified in the 16 samples from sheep. For seven samples, the identification of T. gondii as type II was confirmed by microsatellite typing. The PCR method can be used as an alternative to bioassay for detection and genotyping of T. gondii, and to quantify the organism in meat samples of various sources. PMID- 20350772 TI - Effect of channelling on water balance, oxygen diffusion and oxidation rate in mine waste rock with an inclined multilayer soil cover. AB - Engineered soil covers provide an option to mitigate acid rock drainage through reduced water flow and gaseous oxygen influx to underlying mine waste. Channels such as fissures, cracks or fractures developed in the barrier may influence the long-term performance of the soil cover. However, limited published information is available on the extent to which soil cover performance is impacted by these fissures and cracks. This study was conducted to investigate the effect of channelling in a barrier layer on water flow and oxygen transport in a soil cover. Two inclined (a slope of 20%) multilayer soil covers were examined under laboratory conditions. One cover had a 10-cm wide sand-filled channel in a compacted barrier layer (silty clay) at the upslope section, while the other cover was a normal one without the channel pathway. The soil covers were installed in plastic boxes measuring 120 cm x 120 cm x 25 cm (width x height x thickness). The sand-filled channel was designed to represent the aggregate of fissures and cracks that may be present in the compacted barrier. The soil covers were subjected to controlled drying and wetting periods selected to simulate field situation at the Whistle mine site near Capreol, Ontario, Canada. The measured results indicated that interflow decreased from 72.8% of the total precipitation in the soil cover without channel flow to 35.3% in the cover with channel flow, and percolation increased from zero in the normal soil cover to 43.0% of the total precipitation in the cover with channel flow. Gaseous oxygen transfer into the waste rock below the cover soils was 1091 times greater in the cover with channel than in the soil cover without channel. The channel pathway present in the barrier layer acted as a major passage for water movement and gaseous oxygen diffusion into the waste rock layer, thus decreasing the performance of the soil cover. The spacing of the channel with respect to the length of the test box is similar to those found in other published fracture networks. The distribution and partitioning of the water balance components would be expected to be similar to other situations with the same cover slope. This, of course, would depend on rainfall intensity. PMID- 20350773 TI - Peak torque and rate of torque development in elderly with and without fall history. AB - BACKGROUND: Falls are one of the greatest concerns among the elderly. A number of studies have described peak torque as one of the best fall-related predictor. No studies have comprehensively focused on the rate of torque development of the lower limb muscles among elderly fallers. Then, the aim of this study was to determine the relationship between muscle peak torque and rate of torque development of the lower limb joints in elderly with and without fall history. It was also aimed to determine whether these parameters of muscle performance (i.e., peak torque and rate of torque development) are related to the number of falls. METHODS: Thirty-one women volunteered to participate in the study and were assigned in one of the groups according to the number of falls over the 12 months that preceded the present. Then, participants with no fall history (GI; n=13; 67.6[7.5] years-old), one fall (GII; n=8; 66.0[4.9] years-old) and two or more falls (GIII; n=10; 67.8[8.8] years-old) performed a number of lower limb maximal isometric voluntary contractions from which peak torque and rate of torque development were quantified. FINDINGS: Primary outcomes indicated no peak torque differences between experimental groups in any lower limb joint. The rate of torque development of the knee flexor muscles observed in the non-fallers (GI) was greater than that observed in the fallers (P<0.05) and had a significant relationship with the number of falls (P<0.05). INTERPRETATION: The greater knee flexor muscles' rate of torque development found in the non-fallers in comparison to the fallers indicated that the ability of the elderly to rapidly reorganise the arrangement of the lower limb may play a significant role in allowing the elderly to recover balance after a trip. Thus, training stimulus aimed to improve the rate of torque development may be more beneficial to prevent falls among the elderly than other training stimulus, which are not specifically designed to improve the ability to rapidly produce large amounts of torque. PMID- 20350774 TI - A meta-analytic assessment of Wechsler's P>V sign in antisocial populations. AB - The dichotomy between Verbal IQ and Performance IQ was a hallmark of the Wechsler scales for over 60 years. Wechsler noted that adolescent delinquents tend to score higher on the Performance tests than the Verbal tests (P>V). A plethora of studies have examined the clinical utility of the P>V sign in juvenile delinquents. However, there have been few attempts to systematically quantify the size of this discrepancy in antisocial children and adults. A meta-analysis of 131 studies was conducted to examine whether the PIQ-VIQ discrepancy is found across different age groups as well as sex, race, and test instrument. Results indicated that the discrepancy is characteristic of antisocial females as well as males. The discrepancy is largest in adolescents (6 points), smaller in adults (3 points), and negligible in young children. Furthermore, the effect is moderated by race and instrument, such that the PIQ-VIQ discrepancy is smallest for African Americans and for subjects administered the Wechsler Adult Intelligence Scale. Among adolescents administered the Wechsler Intelligence Scale for Children, the poorest subtests are Vocabulary and Information. It is argued that delinquency is intertwined with school failure, and that verbal-educational deficits accumulate over the course of childhood, eventually manifesting as P>V. PMID- 20350775 TI - Posttraumatic growth and adjustment among individuals with cancer or HIV/AIDS: a meta-analysis. AB - There is increasing research on posttraumatic growth after life-threatening illnesses such as cancer and HIV/AIDS, although it is unclear whether growth confers any psychological or physical benefits in such samples. Consequently, this meta-analysis explored the relationship between posttraumatic growth and psychological and physical wellbeing in adults diagnosed with cancer or HIV/AIDS and examined potential moderators of these relationships. Analysis of 38 studies (N=7927) of posttraumatic growth after cancer or HIV/AIDS revealed that growth was related to increased positive mental health, reduced negative mental health and better subjective physical health. Moderators of these relationships included time since the event, age, ethnicity, and type of negative mental health outcome. It is hoped that this synthesis will encourage further examination of the potentially complex relationship between posttraumatic growth and adjustment in individuals living with life-threatening medical conditions. PMID- 20350776 TI - Gender differences in the relationship between emotional intelligence and right hemisphere lateralization for facial processing. AB - The present study examined relationships between emotional intelligence, measured by the Mayer-Salovey-Caruso Emotional Intelligence Test, and right hemisphere dominance for a free vision chimeric face test. A sample of 122 ethnically diverse college students participated and completed online versions of the forenamed tests. A hierarchical regression was performed to test for the hypothesized interaction between gender and EI on the right hemisphere bias score. No significant main effects were found for gender or total EI score. However, when entered into the model, the interaction term contributed an additional 4.5% of the variance in right hemisphere dominance for the processing of facial emotions. Descriptively, men with greater EI were associated with higher right hemisphere dominance in the free vision test, while no association was observed for women. PMID- 20350777 TI - Real-time detection of DNA cleavage induced by [M(2,2' dipyridylamine)(2)(NO(3))(n)](x+) (M=Cd, Cu, Ni, Zn, n=1,2, x=0,1): effect of central metal ions. AB - [M(Hdpa)(2)(NO(3))(n)](x+) (M=Zn(II), Cd(II), Cu(II) and Ni(II), n=1,2, and x=0, 1) complexes were synthesized, and their activity as catalysts for DNA cleavage reactions were investigated using electrophoresis and linear dichroism technique (LD). All four metal complexes effectively cleaved pBR322 super-coiled DNA. The electrophoresis analysis showed that the [Zn(Hdpa)(2)(NO(3))](+) and [Cd(Hdpa)(2)(NO(3)) (2)] complexes most effectively cleaved the super-coiled DNA, whereas the [Ni(Hdpa)(2)(NO(3))](+) complex was least effective. The magnitude of LD in the DNA absorption region reflects the flexibility and length of DNA when the conditions for measurement are properly adjusted. The double stranded DNA cleavage increases the flexibility of DNA and reduces the length, reducing the magnitude of LD in DNA absorption region. Utilizing this LD property, the cleavage was detected in real-time by measuring the LD magnitude with respect to time. The decrease in the LD magnitude was described as the sum of two exponentials. The fast component was tentatively assigned to the cleavage of the single strand, reflecting the increase in the flexibility of DNA, and the slow component was assigned to the cut of the double strand which reduced the length of DNA. The average reaction time was the fastest for the Zn(II) complex and the slowest for the Ni(II) complex. The reaction time of the Cd(II) complex was as fast as that of the Zn(II) complex. Both the Zn(II) and Cd(II) belong to group 12, suggesting that [M(Hdpa)(2)(NO(3))(n)](x+) with central metal ions from group 12 most efficiently cleaved double stranded DNA. PMID- 20350778 TI - Interaction between ADH1C Arg(272)Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer. AB - Alcohol is a risk factor for breast cancer. We wanted to determine if ADH polymorphisms which modify the rate of ethanol oxidation to acetaldehyde, were associated with breast cancer risk. We matched 809 postmenopausal breast cancer cases with 809 controls, nested within the prospective Diet, Cancer and Health study. Among variant allele carriers of ADH1C Arg(272)Gln, alcohol intake increased the risk of breast cancer with 14% (95% CI: 1.04-1.24) per 10g alcohol/day, but not among homozygous wild type carriers (p for interaction=0.06). Thus, slow oxidation of ethanol seemed to be associated with breast cancer risk. PMID- 20350779 TI - NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells. AB - The transcription factor NF-kappaB is constitutively active in pancreatic adenocarcinoma. Here we explore the contribution of NF-kappaB to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role. Block of NF-kappaB signalling by non-destructible IkappaBalpha rendered cells resistant to TGF-beta-induced epithelial-mesenchymal transition (EMT). In contrast, NF-kappaB activation by TNF-alpha or expression of constitutively active IKK2 induced an EMT-phenotype with up-regulation of vimentin and ZEB1, and down-regulation of E-cadherin. EMT could also be induced in cells with defective TGF-beta signalling. Functional assays demonstrated reduced or strongly enhanced migration and invasion upon NF-kappaB inhibition or activation, respectively. PMID- 20350780 TI - Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells. AB - Hypoxia induces survival signals in hepatocellular carcinoma (HCC). We attempted to find a hypoxia-induced signal that could be used for modulating HCC cell death. Cellular retinoic acid binding protein-II (CRABP-II) expression was significantly increased in hypoxic HCC cells. Treatment with retinoic acid (RA), a ligand for CRABP-II, induced HCC cell apoptosis more effectively in hypoxia than in normoxia, whereas hypoxia-induced CRABP-II expression attenuated RA induced apoptosis. Inhibition of CRABP-II enhanced RA-induced apoptosis and sensitized RA-resistant HCC cells to RA cytotoxicity by attenuating p42/44 MAPK and Akt activation. Therefore, RA/CRABP-II signal modulation is therapeutically implicated in infiltrative HCCs exposed to hypoxia. PMID- 20350781 TI - p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells. AB - Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG(2), and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF kappaB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-kappaB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells. PMID- 20350784 TI - Does insular stroke disrupt the self-medication effects of nicotine? AB - This paper explores the relationship between insular stroke and the disruption of tobacco use. A functional analysis of the role of the insula in maintaining homeostasis suggests that the insula monitors hypoxia and applies dyspnea to motivate the individual to regulate breathing. From its' early usage, nicotine has been used to treat respiratory disorders. It increases respiratory drive, promoting better breathing. Insular stroke likely interferes with this self regulation. A new self-medication model is proposed for tobacco use. The effect on public policy is discussed. PMID- 20350782 TI - Treatment of murine osteoarthritis with TrkAd5 reveals a pivotal role for nerve growth factor in non-inflammatory joint pain. AB - The origin of pain in osteoarthritis is poorly understood, but it is generally thought to arise from inflammation within the innervated structures of the joint, such as the synovium, capsule and bone. We investigated the role of nerve growth factor (NGF) in pain development in murine OA, and the analgesic efficacy of the soluble NGF receptor, TrkAD5. OA was induced in mice by destabilisation of the medial meniscus and pain was assessed by measuring hind-limb weight distribution. RNA was extracted from joints, and NGF and TNF expressions were quantified. The effect of tumour necrosis factor (TNF) and neutrophil blockade on NGF expression and pain were also assessed. NGF was induced in the joints during both post operative (day 3) and OA (16weeks) pain, but not in the non-painful stage of disease (8weeks post-surgery). TrkAd5 was highly effective at suppressing pain in both phases. Induction of NGF in the post-operative phase of pain was TNF dependent as anti-TNF reduced NGF expression in the joint and abrogated pain. However, TNF was not regulated in the late OA joints, and pain was not affected by anti-TNF therapy. Fucoidan, by suppressing cellular infiltration into the joint, was able to suppress post-operative, but not late OA pain. These results indicate that NGF is an important mediator of OA pain and that TrkAd5 represents a potent novel analgesic in this condition. They also suggest that, unlike post operative pain, induction of pain in OA may not necessarily be driven by classical inflammatory processes. PMID- 20350786 TI - A comparison of the prognostic value of early PSA test-based variables following external beam radiotherapy, with or without preceding androgen deprivation: analysis of data from the TROG 96.01 randomized trial. AB - PURPOSE: We sought to compare the prognostic value of early prostate-specific antigen (PSA) test-based variables for the 802 eligible patients treated in the Trans-Tasman Radiation Oncology Group 96.01 randomized trial. METHODS AND MATERIALS: Patients in this trial had T2b, T2c, T3, and T4 N0 prostate cancer and were randomized to 0, 3, or 6 months of neoadjuvant androgen deprivation therapy (NADT) prior to and during radiation treatment at 66 Gy to the prostate and seminal vesicles. The early PSA test-based variables evaluated were the pretreatment initial PSA (iPSA) value, PSA values at 2 and 4 months into NADT, the PSA nadir (nPSA) value after radiation in all patients, and PSA response signatures in men receiving radiation. Comparisons of endpoints were made using Cox models of local progression-free survival, distant failure-free survival, biochemical failure-free survival, and prostate cancer-specific survival. RESULTS: The nPSA value was a powerful predictor of all endpoints regardless of whether NADT was given before radiation. PSA response signatures also predicted all endpoints in men treated by radiation alone. iPSA and PSA results at 2 and 4 months into NADT predicted biochemical failure-free survival but not any of the clinical endpoints. nPSA values correlated with those of iPSA, Gleason grade, and T stage and were significantly higher in men receiving radiation alone than in those receiving NADT. CONCLUSIONS: The postradiation nPSA value is the strongest prognostic indicator of all early PSA-based variables. However, its use as a surrogate endpoint needs to take into account its dependence on pretreatment variables and treatment method. PMID- 20350785 TI - A phase III randomized trial of the timing of meloxicam with iodine-125 prostate brachytherapy. AB - PURPOSE: Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. METHODS AND MATERIALS: From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. RESULTS: Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. CONCLUSIONS: Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization. PMID- 20350788 TI - Measuring interfractional and intrafractional motion with cone beam computed tomography and an optical localization system for lower extremity soft tissue sarcoma patients treated with preoperative intensity-modulated radiation therapy. AB - PURPOSE: To evaluate inter- and intrafractional motion and rotational error for lower extremity soft tissue sarcoma patients by using cone beam computed tomography (CBCT) and an optical localization system. METHODS AND MATERIALS: Thirty-one immobilized patients received CBCT image-guided intensity-modulated radiation therapy. Setup deviations of >3 mm from the planned isocenter were corrected. A second CBCT acquired before treatment delivery was registered to the planning CT to estimate interfractional setup error retrospectively. Interfractional error and rotational error were calculated in the left-right (LR), superoinferior (SI), and anteroposterior (AP) dimensions. Intrafractional motion was assessed by calculating the maximum relative displacement of optical localization system reflective markers placed on the patient's surface, combined with pre- and postfraction CBCT performed for 17 of the 31 patients once per week. The overall systematic error (SE) and random error (RE) were calculated for the interfractional and intrafractional motion for planning target volume margin calculation. RESULTS: The standard deviation (SD) of the interfractional RE was 1.9 mm LR, 2.1 mm SI, and 1.8 mm AP, and the SE SD was 0.6 mm, 1.2 mm, and 0.7 mm in each dimension, respectively. The overall rotation (inter- and intrafractional) had an RE SD of 0.8 degrees LR, 1.7 degrees SI, and 0.7 degrees AP and an SE SD of 1.1 degrees LR, 1.3 degrees SI, and 0.3 degrees AP. The SD of the overall intrafractional RE was 1.6 mm LR, 1.6 mm SI, and 1.4 mm AP, and the SE SD was 0.7 mm AP, 0.6 mm SI, and 0.6 mm AP. CONCLUSIONS: A uniform 5-mm planning target volume margin was quantified for lower extremity soft tissue sarcoma patients and has been implemented clinically for image-guided intensity modulated radiation therapy. PMID- 20350787 TI - Comparative analysis of an image-guided versus a non-image-guided setup approach in terms of delivered dose to the parotid glands in head-and-neck cancer IMRT. AB - PURPOSE: To assess the impact of interfractional variations of shape and setup uncertainties on the dose to the parotid glands (PGs) in head-and-neck cancer intensity-modulated radiotherapy and image-guided radiotherapy (IGRT). METHODS AND MATERIALS: Two scenarios were analyzed retrospectively for 10 head-and-neck cancer patients, treated with helical TomoTherapy (TomoTherapy Inc., Madison, WI): the IGRT scenario and the non-IGRT scenario. The initial dose-volume histograms derived from the planning computed tomography (PCT) scan and 120 recalculated dose-volume histograms of the PGs of each scenario and of corresponding fractions were compared. Setup errors, cumulative median doses (CMDs) for 6 fractions, overall volumes of the PGs, and volumes that received less than 1 Gy or more than 1.6 Gy per fraction were analyzed. RESULTS: The mean decrease in the PG volume was 0.13 cm(3)/d. There was a significantly higher CMD than initially predicted (mean increase for 6 fractions, 1.13 Gy for IGRT and 0.96 Gy for non-IGRT). The volume that received less than 1 Gy per fraction decreased (mean difference to PCT, 1.36 cm(3) for IGRT [p = 0.003] and 1.35 cm(3) for non-IGRT [p = 0.003]) and the volume that received more than 1.6 Gy per fraction increased with increasing fraction number (mean difference to PCT, 1.14 cm(3) for IGRT [p = 0.01] and 1.16 cm(3) for non-IGRT [p = 0.006]). There was no statistically significant difference between the two scenarios (CMD, p = 0.095; volume that received <1 Gy per fraction, p = 0.896; and volume that received >1.6 Gy per fraction, p = 0.855). CONCLUSIONS: In the analyzed group the actual delivered dose to the PGs does not differ significantly between an IGRT and a non IGRT approach. However, IGRT in head-and-neck cancer intensity-modulated radiotherapy is strongly recommended to improve patient setup. PMID- 20350789 TI - Baseline cardiopulmonary function as an independent prognostic factor for survival of inoperable non-small-cell lung cancer after concurrent chemoradiotherapy: a single-center analysis of 161 cases. AB - PURPOSE: Little is known about the effects of cardiopulmonary function on the prognosis of concurrent chemoradiotherapy in patients with inoperable non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: A retrospective analysis of the effects of tumor- and patient-related factors and parameters of cardiopulmonary function and heart morphology on the feasibility, toxicity, and prognosis was performed. RESULTS: Cardiopulmonary function had no effect on the toxicity or feasibility of treatment; effects on survival were observed in the univariate analysis. Median survival varied as follows: cardiac function: 13.0 +/- 1.6 months for left ventricular ejection fraction (LVEF) > 50% vs. 10.0 +/- 1.9 months for LVEF <= 50% (p = 0.003); pulmonary function: 16.0 +/- 0.6 months for no lung function deficits (vital capacity [VC] >= 60%, forced expiratory volume in 1 s >= 80%, and diffusing capacity of the lung for carbon monoxide (DLCO) >=60%) vs. 14.0 +/- 1.5 months for one or two function deficits vs. 8.0 +/- 1.5 months for three lung function deficits (p = 0.001); T stage: 19.0 +/- 3.1 months for rcT0/cT1/cT2 vs. 12.0 +/- 0.8 months for cT3/cT4 (p = 0.039); and age: 11.0 +/- 1.5 months for <60 years vs. 18.0 +/- 2.5 months for 60-69 years vs. 12.0 +/- 1.2 months for >=70 years (p = 0.008). Prognostic factors identified in the multivariate analysis were LVEF <=50% (p = 0.043; hazard ratio [HR], 1.74), reduced pulmonary function (p = 0.001; HR, 1.71 or 5.05) and T stage (p = 0.026; HR: 1.71). CONCLUSIONS: In addition to T-stage, cardiac and pulmonary function variables affected the survival of non-small-cell lung cancer patients after chemoradiotherapy. PMID- 20350790 TI - Phase II study of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. AB - PURPOSE: To investigate the feasibility and efficacy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. METHODS AND MATERIALS: Twenty-four patients with locally advanced esophageal carcinoma were treated with concurrent chemoradiotherapy. A daily fraction of 2.0 Gy was prescribed to a total dose of 60 Gy over 6 weeks. Concurrent paclitaxel (135 mg/m(2), d(1)) and cisplatin (20 mg/m(2), d(1-3)) were administered on Day 1 and Day 29 of the radiotherapy. Erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, was taken by every patient at the dose of 150 mg daily during the chemoradiotherapy. RESULTS: The median follow-up of the 24 patients was 18.6 months (range, 7.1-29.6 months). The 2-year overall survival, local regional control, and relapse-free survival were 70.1% (95% CI, 50.4-90%), 87.5% (95% CI, 73.5-100%), and 57.4% (95% CI, 36.3-78.7%), respectively. During the chemoradiotherapy, the incidences of acute toxicities of Grade 3 or greater, such as leucopenia and thrombocytopenia, were 16.7 % (4/24) and 8.3% (2/24). CONCLUSIONS: Application of concurrent chemoradiotherapy in combination with erlotinib for locally advanced esophageal carcinoma yielded satisfactory 2-year overall survival and local-regional control. The toxicities were well tolerated. PMID- 20350791 TI - Dose-escalation study of single-fraction stereotactic body radiotherapy for liver malignancies. AB - PURPOSE: We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Between February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions. Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas. The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy. Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing risk of death. RESULTS: All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity. Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed. After a median of 17 months follow-up (range, 2-55 months), the cumulative risk of LF at 12 months was 23%. Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died. The median survival was 28.6 months, and the 2-year actuarial overall survival was 50.4%. CONCLUSIONS: It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring <=5 cm. Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity. Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life. PMID- 20350792 TI - Cardiovascular morbidity after radiotherapy or chemoradiation in patients with cervical cancer. AB - PURPOSE: To evaluate the risk of cardiovascular events (CVE) in patients with cervical cancer treated with radiotherapy or chemoradiation. METHODS AND MATERIALS: The incidence of CVE in patients treated between 1989 and 2002 by radiotherapy or chemoradiation was compared with a Dutch reference population. Standardized incidence ratios (SIRs) were calculated for myocardial infarction (MI), angina pectoris (AP), congestive heart failure (CHF), cerebrovascular accident (CVA) separately and for any cardiac event combined (MI, AP, and CHF). RESULTS: In 277 patients with a median follow-up of 4.5 years (range, 0.1-17 years) and a median survival of 9.2 years, 27 cardiac events occurred. The 5-, 10 , and 15-year actuarial incidence of any cardiac event were 9, 14, and 16%, respectively. For the whole population, the SIR for MI was elevated (2.05, 95% CI: 1.12-3.43). The radiotherapy group (n = 132) was older and had more cardiovascular risk factors than the chemoradiation group (n = 145). The SIR for MI in the radiotherapy group was 2.88 (95% CI: 1.44-5.15) and in the chemoradiation group 1.00 (95% CI: 0.21-7.47). In multivariate analyses, there was no relation between treatment modality and the risk for MI. CONCLUSIONS: In this cohort of cervical cancer patients, an increased risk for developing a MI was observed. This increased risk of MI, in combination with the high prevalence of cardiovascular risk factors in cervical cancer patients, urges the need to explore strategies to reduce their risk for cardiovascular morbidity. PMID- 20350793 TI - Squamous cell carcinoma of the anal canal: patterns and predictors of failure and implications for intensity-modulated radiation treatment planning. AB - PURPOSE: Intensity-modulated radiation treatment (IMRT) is increasingly used in the treatment of squamous cell carcinoma of the anal canal (SCCAC). Prevention of locoregional failure (LRF) using IMRT requires appropriate clinical target volume (CTV) definition. To better define the CTV for IMRT, we evaluated patterns and predictors of LRF in SCCAC patients given conventional radiation treatment. METHODS AND MATERIALS: We reviewed records of 180 SCCAC patients treated with conventional radiation with or without chemotherapy at our institution between January 1990 and March 2007. All patients received radiation; the median primary tumor dose was 45 Gy. A total of 173 patients also received mitomycin-based chemotherapy. RESULTS: Median follow-up was 40 months. Actuarial 3-year colostomy free survival was 89% and overall survival (OS) 88%. Actuarial 3-year LRF was 23%. A total of 45 patients had LRF, with 35 (78%) occurring locally in the primary site (25 local only, 10 local and regional); however, 20 (44%) had regional components of failure within the pelvis or inguinal nodes (10 regional only, 10 local and regional). Cumulative sites of LRF (patients may have one or more site of failure) were as follows: primary, 35; inguinal, 8; external perianal, 5; common iliac, 4; presacral, 3; distal rectum, 2; external iliac, 2; and internal iliac, 2. All patients with common iliac failure had cT3 or N+ disease. CONCLUSIONS: The observed patterns of failure support inclusion of the inguinal and all pelvic nodal groups in the CTV for IMRT. In patients with advanced tumor or nodal stage, common iliac nodes should also be included in the CTV. PMID- 20350794 TI - Stability, visibility, and histologic analysis of a new implanted fiducial for use as a kilovoltage radiographic or radioactive marker for patient positioning and monitoring in radiotherapy. AB - PURPOSE: To analyze the stability, visibility, and histology of a novel implantable soft-tissue marker (nonradioactive and radioactive) implanted in dog prostate and rabbit liver. METHODS AND MATERIALS: A total of 34 nonradioactive and 35 radioactive markers were implanted in 1 dog and 16 rabbits. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs at implantation. The IMDs were measured weekly for 4 months in the dog and biweekly for 2-4 weeks in the rabbits. Ultrasound and X-ray imaging were performed on all subjects. Computed tomography and MRI were performed on the dog. Histologic analysis was performed on the rabbits after 2 or 4 months. RESULTS: A total of 139 measurements had a mean (+/- SD) absolute IMD variation of 1.1 +/- 1.1 mm. These IMD variations are consistent with those reported in the literature as due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Histologic analysis revealed that all pathologic changes were highly localized and not expected to be clinically significant. CONCLUSIONS: The markers were stable from the time of implantation. The markers were found to be compatible with all common medical imaging modalities. The markers caused no significant histologic effects. With respect to marker stability, visibility, and histologic analysis these implanted fiducials are appropriate for soft-tissue target positioning in radiotherapy. PMID- 20350796 TI - A comparison of skin and chest wall dose delivered with multicatheter, Contura multilumen balloon, and MammoSite breast brachytherapy. AB - PURPOSE: Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. METHODS AND MATERIALS: 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. RESULTS: The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). CONCLUSION: The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS. PMID- 20350795 TI - Correlation of local failure with measures of dose insufficiency in the high-dose single-fraction treatment of bony metastases. AB - PURPOSE: In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. METHODS AND MATERIALS: The minimum doses received by the hottest 100%, 98%, and 95% (D(min), D(98), and D(95)) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. RESULTS: With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D(min), D(98), and D(95) for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D(min), D(98), and D(95) were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. CONCLUSIONS: The results indicate that D(min), D(98), and D(95) may be important risk factors for local failure. No local failures in any histology were observed when D(min) was >15 Gy, suggesting that this metric may be an important predictor of local control. PMID- 20350797 TI - Increasing age and treatment modality are predictors for subsequent diagnosis of bladder cancer following prostate cancer diagnosis. AB - PURPOSE: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. RESULTS: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. CONCLUSIONS: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted. PMID- 20350798 TI - 18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiotherapy target volume definition in non-small-cell lung cancer: delineation by radiation oncologists vs. joint outlining with a PET radiologist? AB - PURPOSE: (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non-small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist. METHODS AND MATERIALS: RTP PET/CT scans were performed on 28 NSCLC patients (Stage IA-IIIB) of which 14 patients received prior induction chemotherapy. Three radiation oncologists and one PET radiologist working with a fourth radiation oncologist independently delineated the GTV on CT alone (GTV(CT)) and on fused PET/CT images (GTV(PETCT)). The mean percentage volume change (PVC) between GTV(CT) and GTV(PETCT) for the radiation oncologists and the PVC between GTV(CT) and GTV(PETCT) for the PET radiologist were compared using the Wilcoxon signed rank test. Concordance index (CI) was used to assess both positional and volume change between GTV(CT) and GTV(PETCT) in a single measurement. RESULTS: For all patients, a significant difference in PVC from GTV(CT) to GTV(PETCT) exists between the radiation oncologist (median, 5.9%), and the PET radiologist (median, -0.4%, p = 0.001). However, no significant difference in median concordance index (comparing GTV(CT) and GTV(FUSED) for individual cases) was observed (PET radiologist = 0.73; radiation oncologists = 0.66; p = 0.088). CONCLUSIONS: Percentage volume changes from GTV(CT) to GTV(PETCT) were lower for the PET radiologist than for the radiation oncologists, suggesting a lower impact of PET/CT in TV delineation for the PET radiologist than for the oncologists. Guidelines are needed to standardize the use of PET/CT for TV delineation in RTP. PMID- 20350800 TI - Incidental pancreatic lipomas: computed tomography imaging findings with emphasis on diagnostic challenges. AB - PURPOSE: The purpose of this study was to describe the computed tomography (CT) findings of pancreatic lipomas of 9 cases, with emphasis to diagnostic challenges. METHODS: Between March 2006 and April 2008, 9 patients with pancreatic lipomas that were diagnosed by CT were reviewed in the present study. Clinical data and CT features of these 9 cases were retrospectively analysed. The patient population included 5 men and 4 women, aged 42-81 years (mean age, 65.8 years). The patients were followed up for at least 2 years with control CTs. RESULTS: In all 9 cases, a well-bordered nodular fat density lesion was incidentally detected in the pancreas. Four of the lesions had a lobulated contour, and 2 of them had septations. Two of the lipomas were located in the head, 3 in the neck, 3 in the corpus, and 1 in the tail. The CT densitometric values were between -90 and -120 HU, with a mean value of -106 HU. No pancreatic or biliary dilatation or compression to the adjacent structures was seen. All the cases had control CTs, and the lipomas remained unchanged during the follow-up period. Histopathologic confirmation of the diagnosis was not planned for the cases. CONCLUSION: Lipomas are rarely encountered in the pancreas. They often are diagnosed coincidentally as small, well-circumscribed, encapsulated, homogeneous, mature adipose masses on imaging studies. Imaging follow-up strategy or histopathologic confirmation is not necessary in asymptomatic patients. PMID- 20350799 TI - Indolent infectious tenosynovitis afflicting rheumatoid patients treated with tumor necrosis factor inhibitors: case report. AB - Tumor necrosis factor (TNF) is a cytokine associated with the pathogenesis of rheumatoid arthritis. Tumor necrosis factor inhibitors have become important biological treatments that favorably alter the natural history of rheumatoid disease. Side effects include an increased risk of malignancy and infection, particularly tuberculosis. We present 2 patients with rheumatoid arthritis on TNF inhibitors in whom flares of wrist tenosynovitis, initially diagnosed as rheumatoid disease exacerbations, were caused by infections with uncommon opportunistic pathogens. Diagnostic and treatment recommendations for this subset of rheumatoid patients are discussed. PMID- 20350801 TI - Theoretical cost benefits of medical thoracoscopy (MT). PMID- 20350802 TI - Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. AB - To clarify the reciprocal interaction between human-breast cancer metastatic cells and bone microenvironment, we studied the influence of HGF/Met system on a proposed-prognostic marker of aggressiveness, the beta-catenin/Wnt pathway. For in vitro and in vivo experiments we used 1833-bone metastatic clone, derived from human-MDA-MB231 cells. In osteolytic bone metastases and in metastatic cells, Met was expressed in nuclei and at plasma membrane, and abnormally co-localised at nuclear level with beta-catenin and the tyrosine phosphorylated c-Src kinase. Thus, in 1833 cells nuclear-Met COOH-terminal fragment and beta-catenin-TCF were constitutively activated, possibly by receptor and non-receptor tyrosine kinases. The activity of the gene reporter TOPFLASH (containing multiple TCF/LEF-consensus sites) was measured, as index of beta-catenin functionality. In 1833 cells, human and mouse HGF increased Met and beta-catenin tyrosine phosphorylation and expression in nuclear and perinuclear compartments, beta-catenin nuclear translocation via Kank and TOPFLASH transactivation. Human HGF was autocrine/intracrine in bone metastasis, and mouse HGF originating from the adjacent host-bone marrow, was found inside the metastatic nuclei. Parental MDA MB231 cell nuclei did not show functional beta-catenin, for TCF-transactivating activity, and the regulation by HGF. Our study highlighted the importance of the metastasis-stroma interaction in human-breast cancer metastatisation and first identified the HGF/nuclear Met/phospho-c-Src/beta-catenin-TCF/Wnt pathway as a potential-therapeutic target to delay establishment/progression of bone metastases by affecting the aggressive phenotype. PMID- 20350803 TI - Optimization of process conditions with attention to the sludge reduction and stable immobilization in a novel Tubificidae-reactor. AB - A novel Tubificidae-reactor with special porous carrier and combined aeration system was designed to investigate the sludge reduction. The influences of change in frequency of high-intensity aeration (FHIA), dissolved oxygen (DO) content, initial sludge concentration (ISC) and sludge retention time (SRT) on the immobilization of Tubificidae and sludge reduction were evaluated. Furthermore, response surface method was applied to optimize the process conditions using the sludge reduction rate and stable immobilization of worms as the target parameters to optimize, and DO as the control factors to be optimized with the fluctuation of influent ISC, while keeping FHIA and SRT at optimum level. Attractive sludge reduction rate (470 mg L(-1)d(-1)) can be obtained using the strategies indicated by the highly correlated model. The optimum conditions were found to be DO of 1.0 1.6 mg/L and ISC of 3000-4000 mg/L respectively, while keeping FHIA at 12 times/d and SRT at 2d. PMID- 20350804 TI - Potential carbon dioxide fixation by industrially important microalgae. AB - The present study aimed at investigating the carbon metabolism in terms of carbon dioxide fixation and its destination in microalgae cultivations. To this purpose, analysis of growth parameters, media of cultivation, biomass composition and productivity and nutrients balance were performed. Four microalgae suitable for mass cultivation were evaluated: Dunaliella tertiolecta SAD-13.86, Chlorella vulgaris LEB-104, Spirulina platensis LEB-52 and Botryococcus braunii SAG-30.81. Global rates of carbon dioxide and oxygen were determinated by a system developed in our laboratory. B. braunii presented the highest CO(2) fixation rate, followed by S. platensis,D. tertiolecta and C. vulgaris (496.98, 318.61, 272.4 and 251.64 mg L(-1)day(-1), respectively). Carbon dioxide fixated was mainly used for microalgal biomass production. Nitrogen, phosphorus (calcium for D. tertiolecta), potassium and magnesium consumption rates (mg gX(-1)) were evaluated for the four microalgae. Biomass composition presented a predominance of proteins but also a high amount of lipids, especially in D. tertiolecta and B. braunii. PMID- 20350805 TI - A rapid oxime linker-based library approach to identification of bivalent inhibitors of the Yersinia pestis protein-tyrosine phosphatase, YopH. AB - A bivalent tethered approach toward YopH inhibitor development is presented that joins aldehydes with mixtures of bis-aminooxy-containing linkers using oxime coupling. The methodology is characterized by its facility and ease of use and its ability to rapidly identify low micromolar affinity inhibitors. The generality of the approach may potentially make it amenable to the development of bivalent inhibitors directed against other phosphatases. PMID- 20350806 TI - Inhibition of gamma-secretase by the CK1 inhibitor IC261 does not depend on CK1delta. AB - CK1 and gamma-secretase are interesting targets for therapeutic intervention in the treatment of cancer and Alzheimer's disease. The CK1 inhibitor IC261 was reported to inhibit gamma-secretase activity. The question is: Does CK1 inhibition directly influence gamma-secretase activity? Therefore we analyzed the SAR of 15 analogues and their impact on gamma-secretase activity. The most active compounds were investigated on CK1delta activity. These findings exclude a direct influence of CK1delta on gamma-secretase, because any change in the substitution pattern of IC261 diminished CK1 inhibition, whereas gamma-secretase inhibition is still exerted by several analogues. PMID- 20350807 TI - Molecular modelling, synthesis and acetylcholinesterase inhibition of ethyl 5 amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate. AB - In silico analysis of ethyl 5-amino-2-methyl-6,7,8,9 tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate (2) predicts that this molecule should be successfully docked in the PAS, and easily accommodated in the CAS of AChE. The synthesis and the AChE/BuChE inhibition studies are reported, confirming that compound 2 is a potent and selective AChE inhibitor, and consequently, a new lead compound for further development into new dual CAS/PAS cholinergic agents for the treatment of Alzheimer's disease. PMID- 20350808 TI - Bivalent 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolines and -isoquinolinium salts: novel heterocyclic templates for butyrylcholinesterase inhibitors. AB - Three different types of homobivalent compounds, 5,8,9,13b-tetrahydro-6H isoqino[1,2-a]isoquinolines bearing tertiary N-atoms, their quaternary ammonium salts and their dibenzazecine analogues, connected by alkylene spacers of various lengths were synthesized. Compared to the therapeutically used inhibitor galanthamine, some of the bivalent compounds showed much higher inhibitory activities at both cholinesterases in the Ellman test. Surprisingly, not only the quaternary salts, but also the uncharged tertiary compounds exhibited IC(50) values at butyrylcholinesterase in the nanomolar range. Selectivity toward BChE of up to 76-fold was observed. PMID- 20350809 TI - Progressive cerebral white matter involvement in a patient with Congenital Cataracts Facial Dysmorphisms Neuropathy (CCFDN). AB - Congenital Cataracts with Facial Dysmorphisms and Neuropathy (CCFDN) is a complex autosomal recessive disorder characterized by bilateral congenital cataracts, developmental delay, peripheral; hypo-demyelinating neuropathy, mild facial dysmorphisms, and other rare signs. Cerebral and spinal cord atrophy is the main neuroimaging finding but other less common abnormalities have been previously described. We describe progressive focal lesions of supratentorial white matter in a 10-year-old boy affected by CCFDN. Other etiologies have been excluded and these lesions can be considered a new finding of the disease. We discuss a possible demyelinating mechanism affecting both peripheral and central myelin. PMID- 20350810 TI - Alkylation of a human telomere sequence by heterotrimeric chlorambucil PI polyamide conjugates. AB - We designed and synthesized human telomere alkylating N-methylpyrrole-N methylimidazole (PI) polyamide conjugates (1-6). The C-type conjugates 1-3 possessed a chlorambucil moiety at the C terminus, whereas the N-type conjugates 4-6 had one of these moieties at the N terminus. The DNA alkylating activity of these conjugates was evaluated by high-resolution denaturing polyacrylamide gel electrophoresis using a 220bp DNA fragment containing the human telomere repeat sequence 5'-(GGGTTA)(4)-3'/5'-(TAACCC)(4)-3'. C-type conjugates are designed to alkylate the G-rich-strand-containing 5'-GGGTTA-3' and N-type conjugates were designed to alkylate the complementary C-rich strand-containing 5'-TAACCC-3' sequence. The difference between conjugates 1-3 and 4-6 lies in the linker region between the polyamide moiety and chlorambucil. Conjugates 1 and 4 efficiently alkylated the 5'-GGTTAGGGTTA-3' and 5'-CCCTAACCCTAA-3' sequences, respectively, by recognizing 11bp in the presence of distamycin A (Dist), in a heterotrimeric manner: one long alkylating polyamide conjugate (1-6) and two short partners (Dist). PMID- 20350811 TI - Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones. AB - A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33-37, 39-43, and 45 proved to be active DHFR inhibitors with IC(50) range of 0.4-1.0microM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI(50) (MG-MID) concentrations of 11.2, and 24.2microM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the pi-systems in regard to the quinazoline nucleus proved critical for biological activity. PMID- 20350812 TI - Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols. AB - Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1(NL4.3) virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC(50) value of 2.99 and 3.80microM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC(50) value of 2.35microM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC(50) values which indicate that they have better therapeutic indices. PMID- 20350813 TI - Disaccharide derived from chondroitin sulfate A suppressed CpG-induced IL-6 secretion in macrophage-like J774.1 cells. AB - Interleukin (IL)-6 secretion from macrophage cells is known to be induced by toll like receptor (TLR) 9 ligands, CpG (microbial DNA sequences containing unmethylated CpG dinucleotides). We have found, using macrophage-like J774.1 cells, that this induction was dramatically suppressed by a disaccharide derived from chondroitin sulfate A (Di-4S), but not by chondroitin sulfate A (CS-A) itself. The suppression of IL-6 secretion by Di-4S occurred at protein and mRNA expression levels. Di-4S inhibited the degradation of interleukin-1 receptor associated kinase 1 (IRAK1) in the signaling pathway mediated by myeloid differentiation primary response gene (88) (MyD88) when stimulated by TLR9 activation. In addition to suppressing IRAK1 activation, interference with CpG TLR9 interaction by Di-4S is also suggested to be one of the mechanisms. Oligosaccharides derived from chondroitin sulfates would be effective suppressing agents for the TLR9-mediated inflammation reaction. PMID- 20350814 TI - IL-17 is elevated in cerebrospinal fluids in bacterial meningitis in children. AB - Bacterial meningitis has a poor prognosis and neurologic complications. The present study aimed to investigate the cytokine/chemokine network in cerebrospinal fluid (CSF) from children with bacterial meningitis and aseptic meningitis. Interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL 12, IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta, were measured simultaneously in CSF supernatants. We found that, IL-17 was significantly elevated in CSF with bacterial meningitis. We believe that IL-17 plays a key role in neutrophil infiltration into CSF and neuronal protection in bacterial meningitis. PMID- 20350815 TI - Viral safety characteristics of Flebogamma DIF, a new pasteurized, solvent detergent treated and Planova 20 nm nanofiltered intravenous immunoglobulin. AB - A new human liquid intravenous immunoglobulin product, Flebogamma DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log(10) TCID(50)) or Plaque Forming Units assay (log(10) PFU). Validation studies demonstrated that each specific step cleared more than 4 log(10) for all viruses assayed. An overall viral clearance between > or =13.33 log(10) and > or =25.21 log(10), was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma DIF has a very high viral safety profile. PMID- 20350817 TI - HIV screening: beliefs and intentions of the homeless. AB - HIV screening is the first step in identifying HIV infection; however, the HIV screening rates remain low. Homeless people in the United States are at risk for HIV infection, yet their acceptance of HIV screening remains poorly understood. The purpose of this study was to investigate beliefs and intentions of the homeless toward HIV screening. Using a survey design, this study applied the Theory of Planned Behavior to investigate attitudes, social norms, and perceived behavioral control and their relationship to intention to screen for HIV. Homeless people (N = 323) from 12 different shelters participated in this study. The final path analysis explained 60% of homeless people's intentions to screen for HIV. Significant predictors included: attitude toward HIV screening, prior screening, age, and subjective norms. Implications include health provider recommendations for screening and increasing awareness of HIV risk behaviors for this vulnerable population. PMID- 20350816 TI - A critical review of HIV-related interventions for women prisoners in the United States. AB - This article reviews the literature on HIV-related interventions for U.S. women prisoners, with a focus on identifying strategies that enabled women to practice safer sex, reduce drug use, and to avoid recidivism. A comprehensive search indicated that only nine such interventions were evaluated in professional journals between 1994 and 2009. These interventions involved behavioral programs for women at risk for HIV and discharge planning for women releases who were either infected with or at risk for HIV. Four interventions for incarcerated women achieved successful outcomes regarding self-empowerment and safer sex skills; 3 prison-release interventions resulted in less recidivism if not reduced HIV risk. Each intervention was nominally women-centered, with prison-release programs lacking protocols that were designed specifically for women. Based on evidence that women-centered interventions were desirable for this population, such interventions should be given high priority in criminal justice policy and care provision during the HIV epidemic. PMID- 20350818 TI - Peroneal subluxation: surgical results in 31 athletic patients. AB - Few studies describe the results of surgical treatment of peroneal retinaculum in athletic populations. Thirty-one athletic patients with symptomatic subluxating peroneal tendons were treated surgically by one surgeon with isolated subluxation repair, subluxation repair plus peroneus brevis tendon repair, or subluxation repair plus lateral ankle stabilization. As a group, the average time to return to activity was 3.2 +/- 0.8 months with a postoperative AOFAS score of 97.0 +/- 5.3. Patients with tendon tears were older in age (P < .01) and took longer to return to activity than the rest of the cohort (P = .02). There were a total of 4 patients with postoperative complications, although all were able to return to sports. The patients with peroneal subluxation in this study were able to return to their sport in approximately 3 months. Those with concomitant tendon tears took longer. Further study is needed to see if this is associated with longer standing symptoms. PMID- 20350819 TI - Outcome following autogenous soft tissue interpositional arthroplasty for end stage hallux rigidus: a systematic review. AB - Autogenous soft tissue interpositional arthroplasty has been proposed as an alternative to arthrodesis and other forms of arthroplasty for treatment of end stage hallux rigidus because of the perceived safety and efficacy. The author undertook a systematic review of electronic databases and other relevant sources to identify material relating to the outcomes following autogenous soft tissue interpositional arthroplasty for end-stage hallux rigidus. Information from peer reviewed journals, as well as from non-peer-reviewed publications, abstracts and posters, textbooks, and unpublished works, were also considered. In an effort to procure the highest quality studies available, studies were eligible for inclusion only if they involved consecutively enrolled patients undergoing isolated autogenous soft tissue interpositional arthroplasty for the treatment of end-stage hallux rigidus, evaluated patients at mean follow-up of 12-months' duration or longer, included pre- and postoperative range of motion of the first metatarsal-phalangeal joint, determined pre- and postoperative outcomes using a scoring system, and documented any complications. Two studies involving a total of 28 autogenous soft tissue interpositional arthroplasties for end-stage hallux rigidus were identified that met the inclusion criteria. There were 12 men (52%) and 11 women (48%) with a mean age of 58.2 years followed for a mean of 21.6 months. Both studies used the AOFAS First Metatarsal-Phalangeal-Hallux Scoring System, which had a mean of 26.0 preoperatively rising to 89.4 postoperatively. First metatarsal-phalangeal joint dorsiflexion had a mean of 16.7 degrees preoperatively rising to 51.1 degrees postoperatively. Complications occurred in 4 (14.3%) feet and no feet required surgical revision. The results of this systematic review demonstrate improvement in patient outcomes and first metatarsal-phalangeal joint dorsiflexion, as well as few complications following autogenous soft tissue interpositional arthroplasty for end-stage hallux rigidus. However, there is still a need for methodologically sound prospective cohort studies that compare autogenous soft tissue interpositional arthroplasty with other forms of arthroplasty and arthrodesis for end-stage hallux rigidus. PMID- 20350820 TI - Arthroscopic treatment of anterolateral impingement of the ankle. AB - Anterolateral ankle impingement is due to entrapment of pathological tissues in the anterolateral aspect of the joint. The aim of this study was to evaluate the results of arthroscopic diagnosis and treatment of anterolateral ankle impingement. Twenty patients with anterolateral ankle impingement who had arthroscopic debridement were included in this prospective study, including 16 men and 4 women with a mean age of 35.8 years. Synovial hypertrophy was found in 13 patients, impinging distal fascicle of the anterior inferior tibiofibular ligament in 2 patients, torn anterior inferior tibiofibular ligament in 3 patients, and fibrofatty scar tissue in 2 patients. Seven patients had associated talar cartilage damage. Four patients had additional inversion injuries after the arthroscopic procedures. Final results were excellent in 11 patients, good in 6 patients, fair in 2 patients, and poor in 1 patient. One of the 7 patients with cartilage damage had excellent results, 5 patients had good results, and the remaining patient had fair results. Two of the 3 patients with complete tear of the anterior inferior tibiofibular ligament had fair results, and the other had a poor result. One of the 4 patients with additional inversion injuries had good results, 2 had fair results, and 1 had a poor result. In conclusion, ankle arthroscopy is useful in the diagnosis and treatment of anterolateral ankle impingement. Factors that negatively affect final outcome are associated chondral lesions of the talus, associated syndesmotic lesions, and new inversion injuries after the arthroscopic procedure. PMID- 20350821 TI - Calcaneal chondroblastoma with secondary aneurysmal bone cyst: a case report. AB - We present a case of destructive chondroblastoma associated with secondary aneurysmal bone cyst involving the left calcaneus. Because of the extensive destruction of the calcaneus, total calcanectomy was the treatment of choice. PMID- 20350822 TI - Reconstruction of massive midfoot bone and soft tissue loss as a result of blast injury. AB - Lower extremity blast injuries represent a unique challenge to surgeons and often involve complex, limb-threatening wounds with extensive soft tissue and bone loss. Surgical treatment of these injuries can be difficult because of limited autogenous resources for reconstruction of the defect. In this article, we describe a technique for medial column reconstruction using iliac crest bone graft and soft tissue coverage with an abductor hallucis rotational flap combined with a split-thickness skin graft. This method addresses the extensive bone and soft tissue defects that frequently characterize blast injuries to the foot, and may be applicable in other situations where trauma or infection has caused extensive destruction of the medial column. PMID- 20350823 TI - Time well spent. PMID- 20350824 TI - The need for surgical revision after isolated valenti arthroplasty for hallux rigidus: a systematic review. AB - Isolated Valenti arthroplasty has been proposed for treatment of moderate to severe hallux rigidus because of the perceived safety and efficacy. Furthermore, it has been proposed that undergoing isolated Valenti arthroplasty does not prevent the ability to perform revision surgery consisting of Keller resection arthroplasty, prosthetic implant arthroplasty, or arthrodesis. The author undertook a systematic review of electronic databases and other relevant sources to identify material relating to the need for surgical revision after isolated Valenti arthroplasty for hallux rigidus. Information from peer-reviewed journals as well as non-peer-reviewed publications, abstracts, and posters was also considered. In an effort to procure the highest quality studies available, studies were eligible for inclusion only if they involved consecutively enrolled patients undergoing isolated Valenti arthroplasty, if they evaluated patients in person at mean follow-up > or = 12 months' duration, and if they included details of complications after Valenti arthroplasty requiring surgical intervention. Three studies involving isolated Valenti arthroplasty were identified that met the inclusion criteria. Therefore, a total of 44 isolated Valenti arthroplasties were identified that met the inclusion criteria, with 2 (4.6%) undergoing surgical revision in the form of Keller resection arthroplasty (n = 1) and 1 plantarflexory base osteotomy (n = 1). No studies provided detailed information regarding complications specific to the exact grade of hallux rigidus in patients who underwent isolated Valenti arthroplasty. The results of this systematic review make clear the low incidence of revision surgery required after isolated Valenti arthroplasty for hallux rigidus. However, there is still a need for methodologically sound prospective cohort studies that focus on the use of isolated Valenti arthroplasty for specific grades of hallux rigidus and compare this procedure with other accepted forms of surgical treatment for moderate to severe hallux rigidus. PMID- 20350825 TI - Morphology of the adult midsagittal brainstem in relation to the reference systems MRI-based variability study. AB - RATIONALE AND OBJECTIVES: Anterior/posterior commissure reference system (AC/PC reference system) and the fastigium/ventricular floor plane reference system (FFL/VFL reference system) are two reference systems used in the stereotactic localization of the invisible nuclei of the brainstem in magnetic resonance (MR) images. This study investigated the variation of the midsagittal brainstem in relation to the AC/PC and VFL/FFL reference systems with respect to age and gender. MATERIALS AND METHODS: High-resolution T1-weighted structural MR images were acquired from 64 adults (age range 21-60 years, 32 males and 32 females). The AC/PC and VFL/FFL reference systems were identified automatically. A set of landmarks of the midsagittal brainstem were defined and localized interactively. RESULTS: Results illustrated that there was significant difference between the variance of the anteroposterior coordinate of the landmarks in relation to the AC/PC reference system and that in relation to the FFL/VFL reference system (P < .05), the former is larger than the latter. The positions of the landmarks in the females are more anterior than those in the males in relation to the AC/PC reference (P < .05); the difference in relation to the FFL/VFL reference system was not found. CONCLUSION: Either the FFL/VFL reference system or the AC/PC reference system has its own advantage in the stereotactic localization of the structure in the brainstem. PMID- 20350826 TI - Diffusion-weighed MR of the thyroid gland in Graves' disease: assessment of disease activity and prediction of outcome. AB - RATIONALE AND OBJECTIVES: To assess the activity and clinical course of Graves' disease with diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-one patients with Graves' disease and 25 volunteers underwent diffusion MR imaging of the thyroid gland using a single shot echo-planar imaging with b-factor of 0, 300 and 600 second/mm(2). The apparent diffusion coefficient (ADC) values of the thyroid gland were calculated. Patients with active Graves' disease included untreated patients at initial diagnosis (n = 12), patients under antithyroid drugs (n = 11), and patients in relapse after withdrawal of therapy (n = 13). Patients with inactive disease had a remission of hyperthyroidism (n = 15). RESULTS: The mean ADC values of thyroid gland with active Graves' disease was 0.65 +/- 0.03 x 10(-3) mm(2)/second in patients at initial diagnosis, 0.81 +/ 0.02 x 10(-3) mm(2)/second in patients undergoing antithyroid drug and 0.72 +/- 0.07 x 10(-3) mm(2)/second in patients with relapse of hyperthyroidism. The mean ADC of patients with remission was 0.94 +/- 0.03 x 10(-3) mm(2)/second and for normal volunteer was 1.06 +/- 0.08 x 10(-3) mm(2)/second. There was significant difference in the ADC value of patients with active disease and remission (P = .001). The cutoff ADC value used for differentiating patients with active disease from patients with remission was 0.82 x 10(-3) mm(2)/second. The mean ADC value of thyroid gland had positive correlation with thyroid-stimulating hormone (r = 0.87, P = .001) and negative correlation with serum T4 (r = -0.82, P = .001) and serum T3 (r = -0.71, P = .001). CONCLUSIONS: The ADC value of the thyroid gland is a promising non invasive parameter for diagnosis of different clinical stages of Graves' disease. Hence it can be used to assess the activity and predict the outcome of patients during and after medical treatment. PMID- 20350827 TI - The visiting professorship: to Fargo and beyond. PMID- 20350828 TI - Foot-and-mouth disease: the question of implementing vaccinal control during an epidemic. AB - The question of whether or not to use vaccines during an epidemic of foot-and mouth disease (FMD) has interested veterinary administrators for many decades. This review assesses the historical uses, successes and failures of vaccinal control, and addresses the questions of where, how, and when to use vaccination against FMD. Approaching the problem in this manner can aid in identifying which tools are likely to be most effective during an epidemic, and how successful a given contingency plan might be. The infection status (endemic, semi-endemic, disease-free) of a region has historically mapped where global vaccination has been implemented according to the generality: endemic>semi-endemic>disease-free. More specifically, biomodels and cost-benefit analyses can indicate when vaccination should be implemented for optimal disease control. Finally, numerous local epidemiological factors will provide useful insights into how vaccinal controls can be used effectively. PMID- 20350829 TI - Acute disseminated encephalomyelitis: a 10-year cohort study in Thai children. AB - Childhood acute disseminated encephalomyelitis (ADEM) is a demyelinating disease with variable clinical courses and outcomes. Its evolution to multiple sclerosis in Asian children is yet to be determined. Medical records, investigation results and magnetic resonance imaging of brain of Thai children aged less than 15 years with initial diagnosis of ADEM at a referral university hospital in Thailand from January 1997 to December 2006 were reviewed. Clinical course and the outcome were finalized by telephone interview, self-report questionnaire, and/or neurological examination by December 2008. Modified Rankin Score was applied for determination of disability. MRI findings were categorized along with the locations and number of areas of abnormalities shown by T2-weight and FLAIR. 16 patients consisting of 5 boys and 11 girls (age-range 1-14 years, mean 6.9 +/- 3.6 years, median 6 years) were identified. Nine patients had cranial nerve dysfunctions including one child with optic neuropathy. One patient died with confirmed pathological diagnosis of ADEM. Among the remaining 15, who were followed from 2 to 10 years (mean 5.8 years), 13 and 3 patients were classified into monophasic ADEM and multiple sclerosis, respectively. Ten of 13 with final diagnosis of ADEM had complete recovery. There was no association between number of lesions or location in the initial MRI and the outcome and final diagnosis. ADEM in Thai children had similar clinical presentation and outcome to previous studies in Western countries. ADEM can occasionally evolve to multiple sclerosis in Thai children as being shown in previous reports from other Asian countries. PMID- 20350830 TI - Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. AB - Endothelins (ETs) contribute to the sensory changes seen in animals models of inflammatory, cancer and diabetic neuropathic pain, but little is known about their nociceptive role following peripheral nerve injury. The current study evaluated mechanisms by which ETs can drive changes in nociceptive responses to thermal stimulation of the hind paw of rats induced by unilateral lumbar L5/L6 spinal nerve ligation (SNL) injury. SNL sensitizes rats to acetone-evoked cooling of and radiant heat application (Hargreaves test) to the ipsilateral hind paw (throughout 3-40 and 9-40 days after surgery, respectively). At 12 days after SNL, intraplantar (i.pl.) injection of endothelin-1 (ET-1, 10 pmol) induces greater overt nociception that was reduced only by treatment with the selective ET(A) peptidic antagonist (BQ-123, 10 nmol, i.pl), but unchanged by the selective ET(B) peptidic antagonist (BQ-788). Cold allodynia evoked by cooling the ipsilateral hind paw with acetone was reduced by i.pl. injection of both antagonists BQ-123 or BQ-788 (3 or 10 nmol). In contrast, heat hyperalgesia evaluated by Hargreaves method was reduced only by BQ-123. SNL enhanced the [Ca(+2)](i) increases induced by ET-1 (100 nM) in neurons from L5/L6 (injured) and L4 (intact) cultured dorsal root ganglion, but did not change the responses of non-neuronal cells. Furthermore, Western blot analysis revealed that SNL increased ET(A) and ET(B) receptor protein expression in spinal nerves. Thus, SNL induces marked hind paw hypersensitivity to thermal stimulation in part via up regulation of peripheral sensory nerve pronociceptive ET(A) and ET(B) receptor operated mechanisms. PMID- 20350832 TI - Amantadine-associated corneal edema. PMID- 20350831 TI - OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. AB - 3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Here we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown, but it contains a putative mitochondrial leader sequence, mitochondrial sorting signal and a peroxisomal sorting signal. Our green fluorescent protein tagged OPA3 expression studies found its localization to be predominantly mitochondrial. These findings thus place the cellular metabolic defect of 3-MGCA type III in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology. PMID- 20350834 TI - Oral healthcare in people living with cancer. PMID- 20350833 TI - A coupled deformable model for tracking myocardial borders from real-time echocardiography using an incompressibility constraint. AB - Real-time three-dimensional (RT3D) echocardiography is a new image acquisition technique that allows instantaneous acquisition of volumetric images for quantitative assessment of cardiac morphology and function. To quantify many important diagnostic parameters, such as ventricular volume, ejection fraction, and cardiac output, an automatic algorithm to delineate the left ventricle (LV) from RT3D echocardiographic images is essential. While a number of efforts have been made towards segmentation of the LV endocardial (ENDO) boundaries, the segmentation of epicardial (EPI) boundaries remains problematic. In this paper, we present a coupled deformable model that addresses this problem. The idea behind our method is that the volume of the myocardium is close to being constant during a cardiac cycle and our model uses this coupling as an important constraint. We employ two surfaces, each driven by the image-derived information that takes into account ultrasound physics by modeling the speckle statistics using the Nakagami distribution while maintaining the coupling. By simultaneously evolving two surfaces, the final segmentation of the myocardium is thus achieved. Results from 80 sets of synthetic data and 286 sets of real canine data were evaluated against the ground truth and against outlines from three independent observers, respectively. We show that results obtained with our incompressibility constraint were more accurate than those obtained without constraint or with a wall thickness constraint, and were comparable to those from manual segmentation. PMID- 20350835 TI - Overview of cancer for the healthcare team: aetiopathogenesis and early diagnosis. AB - Much cancer presents late, at a stage when not only is more radical treatment necessary, but the prognosis is also less favourable. This paper attempts to provide an overview of the aetiopathogenesis of cancer (carcinoma) for the healthcare team, a broad understanding of which is crucial for coping with issues related to prevention, diagnosis and management. Prevention of cancer involves lifestyle decisions which afford protection not only against cancers in many sites, but also against a wide range of other conditions, many of which are equally life-threatening. The paper also highlights areas of controversy in the early diagnosis of oral cancer. Earlier diagnosis is likely to be achieved reliably only with the introduction of molecular studies. PMID- 20350836 TI - Slow (1 Hz) repetitive transcranial magnetic stimulation (rTMS) induces a sustained change in cortical excitability in patients with Parkinson's disease. AB - OBJECTIVE: Low-frequency (< or =1 Hz) rTMS (LF-rTMS) can reduce excitability in the underlying cortex and/or promote inhibition. In patients with Parkinson's disease (PD) several TMS elicited features of motor corticospinal physiology suggest presence of impaired inhibitory mechanisms. These include shortened silent period (SP) and slightly steeper input-output (I-O) curve of motor evoked potential (MEP) size than in normal controls. However, studies of LF-rTMS effects on inhibitory mechanisms in PD are scarce. In this companion paper to the clinical paper describing effects of four consecutive days of LF-rTMS on dyskinesia in PD (Filipovic et al., 2009), we evaluate the delayed (24h) effects of the LF-rTMS treatment on physiological measures of excitability of the motor cortex in the same patients. There are very few studies of physiological follow up of daily rTMS treatments. METHODS: Nine patients with PD in Hoehn and Yahr stages 2 or 3 and prominent medication-induced dyskinesia were studied. This was a placebo-controlled, crossover study, with two treatment arms, "real" rTMS and "sham" rTMS (placebo). In each of the treatment arms, rTMS (1800 pulses; 1 Hz rate; intensity of the real stimuli just-below the active motor threshold) was delivered over the motor cortex for four consecutive days. Motor cortex excitability was evaluated at the beginning of the study and the next day following each of the four-day rTMS series (real and sham) with patients first in the practically defined "off" state, following 12h withdrawal of medication, and subsequently in a typical "on" state following usual morning medication dose. RESULTS: The SP was significantly longer following real rTMS in comparison to both baseline and sham rTMS. The effect was independent from the effects of dopaminergic treatment. There was no difference in MEP size, rest and active motor threshold. The I-O curve, recorded from the relaxed muscle, showed a trend towards diminished slope in comparison to baseline, but the difference was not significant. There was no consistent correlation between prolongation of SP and concomitant reduction in dyskinesia following real rTMS. CONCLUSIONS: Low frequency rTMS delivered over several consecutive days changes the excitability of motor cortex by increasing the excitability of inhibitory circuits. The effects persist for at least a day after rTMS. SIGNIFICANCE: The results confirm the existence of a residual after-effect of consecutive daily applications of rTMS that might be relevant to the clinical effect that was observed in this group of patients and could be further exploited for potential therapeutic uses. PMID- 20350837 TI - Human retinal pigment epithelium-induced CD4+CD25+ regulatory T cells suppress activation of intraocular effector T cells. AB - Murine retinal pigment epithelial (RPE) cells suppress T-cell activation by releasing soluble inhibitory factors and promote the generation of regulatory T cells in vitro. These T cells exposed to RPE supernatants (RPE-induced Treg cells) can suppress the activation of bystander effector T cells via the production of transforming growth factor-beta (TGFbeta). In the present study, we showed that human RPE-induced Treg cells are also able to acquire regulatory function when human RPE cell lines were pretreated with recombinant TGF beta 2. These RPE-induced Treg cells produced TGF beta 1 and IL-10 but not IFN gamma, and they significantly suppressed the activation of target cell lines and intraocular T-cell clones established from patients with active uveitis. Moreover, CD4(+)CD25(+) RPE-induced Treg cells expressed CTLA-4 and Foxp3 molecules, and the CD25(+) Treg cells profoundly suppressed the T-cell activation. Thus, in vitro manipulated Treg cells acquire functions that participate in the establishment of immune tolerance in the eye. PMID- 20350838 TI - Late termination of pregnancy and foetal reduction for foetal anomaly. AB - Late termination of pregnancy is a relatively rare procedure accounting for approximately 1% of all registered terminations in England and Wales; however, with improving detection rates for foetal anomalies, this number is increasing. Surgical dilation and evacuation (D&E) appears to be a safe and cost-effective procedure as long as the clinical expertise exists to provide this service. Medical termination appears equally safe and is best undertaken with the combined use of mifepristone and misoprostol. Foeticide, when required, should be performed from 22 weeks' gestation using strong KCl administered either by cardiocentesis or by cordocentesis. All women should be offered a post-mortem and any other appropriate investigation to allow accurate counselling regarding future pregnancies. The issue of late selective foetal reduction for foetal abnormality is complicated by the need to balance the risks to the healthy co twin of expectant management versus selective termination. PMID- 20350839 TI - Effects and mechanisms of acupuncture in the reproductive system. AB - The use of acupuncture to treat reproductive dysfunction has not been well investigated. Only a few clinical studies have been reported, most of which are flawed by poor design and a lack of valid outcome measures and diagnostic criteria, making the results difficult to interpret. Experimental studies, however, show that acupuncture has substantial effects on reproductive function. Here we review the possible mechanisms of action of acupuncture on the reproductive system and its effects on reproductive dysfunction, focusing in particular on polycystic ovary syndrome, the most common endocrine and metabolic disorder in women. Clinical and experimental evidence demonstrates that acupuncture is a suitable alternative or complement to pharmacological induction of ovulation, without adverse side effects. Clearly, acupuncture modulates endogenous regulatory systems, including the sympathetic nervous system, the endocrine system, and the neuroendocrine system. Randomized clinical trials are warranted to further evaluate the clinical effects of acupuncture in reproductive disorders. PMID- 20350840 TI - Spatially adaptive mixture modeling for analysis of FMRI time series. AB - Within-subject analysis in fMRI essentially addresses two problems, the detection of brain regions eliciting evoked activity and the estimation of the underlying dynamics. In Makni et aL, 2005 and Makni et aL, 2008, a detection-estimation framework has been proposed to tackle these problems jointly, since they are connected to one another. In the Bayesian formalism, detection is achieved by modeling activating and nonactivating voxels through independent mixture models (IMM) within each region while hemodynamic response estimation is performed at a regional scale in a nonparametric way. Instead of IMMs, in this paper we take advantage of spatial mixture models (SMM) for their nonlinear spatial regularizing properties. The proposed method is unsupervised and spatially adaptive in the sense that the amount of spatial correlation is automatically tuned from the data and this setting automatically varies across brain regions. In addition, the level of regularization is specific to each experimental condition since both the signal-to-noise ratio and the activation pattern may vary across stimulus types in a given brain region. These aspects require the precise estimation of multiple partition functions of underlying Ising fields. This is addressed efficiently using first path sampling for a small subset of fields and then using a recently developed fast extrapolation technique for the large remaining set. Simulation results emphasize that detection relying on supervised SMM outperforms its IMM counterpart and that unsupervised spatial mixture models achieve similar results without any hand-tuning of the correlation parameter. On real datasets, the gain is illustrated in a localizer fMRI experiment: brain activations appear more spatially resolved using SMM in comparison with classical general linear model (GLM)-based approaches, while estimating a specific parcel-based HRF shape. Our approach therefore validates the treatment of unsmoothed fMRI data without fixed GLM definition at the subject level and makes also the classical strategy of spatial Gaussian filtering deprecated. PMID- 20350841 TI - Linear and nonlinear projective nonnegative matrix factorization. AB - A variant of nonnegative matrix factorization (NMF) which was proposed earlier is analyzed here. It is called projective nonnegative matrix factorization (PNMF). The new method approximately factorizes a projection matrix, minimizing the reconstruction error, into a positive low-rank matrix and its transpose. The dissimilarity between the original data matrix and its approximation can be measured by the Frobenius matrix norm or the modified Kullback-Leibler divergence. Both measures are minimized by multiplicative update rules, whose convergence is proven for the first time. Enforcing orthonormality to the basic objective is shown to lead to an even more efficient update rule, which is also readily extended to nonlinear cases. The formulation of the PNMF objective is shown to be connected to a variety of existing NMF methods and clustering approaches. In addition, the derivation using Lagrangian multipliers reveals the relation between reconstruction and sparseness. For kernel principal component analysis (PCA) with the binary constraint, useful in graph partitioning problems, the nonlinear kernel PNMF provides a good approximation which outperforms an existing discretization approach. Empirical study on three real-world databases shows that PNMF can achieve the best or close to the best in clustering. The proposed algorithm runs more efficiently than the compared NMF methods, especially for high-dimensional data. Moreover, contrary to the basic NMF, the trained projection matrix can be readily used for newly coming samples and demonstrates good generalization. PMID- 20350842 TI - Fast cartoon + texture image filters. AB - Can images be decomposed into the sum of a geometric part and a textural part? In a theoretical breakthrough, [Y. Meyer, Oscillating Patterns in Image Processing and Nonlinear Evolution Equations. Providence, RI: American Mathematical Society, 2001] proposed variational models that force the geometric part into the space of functions with bounded variation, and the textural part into a space of oscillatory distributions. Meyer's models are simple minimization problems extending the famous total variation model. However, their numerical solution has proved challenging. It is the object of a literature rich in variants and numerical attempts. This paper starts with the linear model, which reduces to a low-pass/high-pass filter pair. A simple conversion of the linear filter pair into a nonlinear filter pair involving the total variation is introduced. This new-proposed nonlinear filter pair retains both the essential features of Meyer's models and the simplicity and rapidity of the linear model. It depends upon only one transparent parameter: the texture scale, measured in pixel mesh. Comparative experiments show a better and faster separation of cartoon from texture. One application is illustrated: edge detection. PMID- 20350843 TI - Exploring duplicated regions in natural images. AB - Duplication of image regions is a common method for manipulating original images, using typical software like Adobe Photoshop, 3DS MAX, etc. In this study, we propose a duplication detection approach that can adopt two robust features based on discrete wavelet transform (DWT) and kernel principal component analysis (KPCA). Both schemes provide excellent representations of the image data for robust block matching. Multiresolution wavelet coefficients and KPCA-based projected vectors corresponding to image-blocks are arranged into a matrix for lexicographic sorting. Sorted blocks are used for making a list of similar point pairs and for computing their offset frequencies. Duplicated regions are then segmented by an automatic technique that refines the list of corresponding point pairs and eliminates the minimum offset-frequency threshold parameter in the usual detection method. A new technique that extends the basic algorithm for detecting Flip and Rotation types of forgeries is also proposed. This method uses global geometric transformation and the labeling technique to indentify the mentioned forgeries. Experiments with a good number of natural images show very promising results, when compared with the conventional PCA-based approach. A quantitative analysis indicate that the wavelet-based feature outperforms PCA- or KPCA-based features in terms of average precision and recall in the noiseless, or uncompressed domain, while KPCA-based feature obtains excellent performance in the additive noise and lossy JPEG compression environments. PMID- 20350844 TI - Hybrid associative retrieval of three-dimensional models. AB - In this paper, we propose a novel 3-D model retrieval framework, which is referred to as hybrid 3-D model associative retrieval. Unlike the conventional 3 D model similarity retrieval approach, the query model and the models obtained by 3-D model hybrid associative retrieval have the following properties: They belong to different model classes and have different shape characteristics in general but are semantically related and preassembled in a certain associative group. For instance, given a furniture associative group { desk, chair, bed}, we may probably like to use a desk as a query model to search for a list of matching models, which belong to the chair or bed class. We consider the following possibilities: 1) there can be more than two classes in an association group and 2) different association groups might have different numbers of classes. The hybrid associative retrieval is performed in two stages: 1) to establish the relationship between different 3-D model categories with semantic associations, we propose three approaches based on neural network learning and 2) to address the aforementioned two conditions, we use a cyclic-shift scheme to partition different associative groups into two-class pairwise associative groups and then adopt two different strategies to combine the final retrieval results. Experiments by using different data sets demonstrate the effectiveness and efficiency of our proposed framework on the new hybrid associative retrieval task. PMID- 20350845 TI - Action selection for single-camera SLAM. AB - A method for evaluating, at video rate, the quality of actions for a single camera while mapping unknown indoor environments is presented. The strategy maximizes mutual information between measurements and states to help the camera avoid making ill-conditioned measurements that are appropriate to lack of depth in monocular vision systems. Our system prompts a user with the appropriate motion commands during 6-DOF visual simultaneous localization and mapping with a handheld camera. Additionally, the system has been ported to a mobile robotic platform, thus closing the control-estimation loop. To show the viability of the approach, simulations and experiments are presented for the unconstrained motion of a handheld camera and for the motion of a mobile robot with nonholonomic constraints. When combined with a path planner, the technique safely drives to a marked goal while, at the same time, producing an optimal estimated map. PMID- 20350846 TI - Noninvasive focused monitoring and irradiation of head tissue phantoms at microwave frequencies. AB - In this study, new aspects of our research regarding a novel hybrid system able to provide focused microwave radiometric temperature and/or conductivity measurements and hyperthermia treatment via microwave irradiation are presented. On one hand, it is examined whether the system is capable of sensing real-time progressive local variations of temperature and/or conductivity in customized phantom setups; on the other hand, the focusing attributes of the system are explored for different positions and types of phantoms used for hyperthermia in conjunction with dielectric matching layers surrounding the areas of interest. The main module of the system is an ellipsoidal cavity, which provides the appropriate focusing of the electromagnetic energy on the area of interest. The system has been used for the past few years in experiments with different configuration setups including phantom, animal, and human volunteer measurements yielding promising outcome. The present results show that the system is able to detect local concentrated gradual temperature and conductivity variations expressed as an increase of the output radiometric voltage. Moreover, when contactless focused hyperthermia is performed, the results show significant temperature increase at specific phantom areas. In this case, the effect of the dielectric matching layers placed around the phantoms is critical, thus resulting in the enhancement of the energy penetration depth. PMID- 20350847 TI - Local hemodynamics and intimal hyperplasia at the venous side of a porcine arteriovenous shunt. AB - Venous anastomotic intimal hyperplasia (IH) observed in the arteriovenous shunt (AVS) has been associated with disturbed hemodynamics. This study aims to correlate hemodynamics with wall histology and wall mechanics by examining the flow field in AVS with computational fluid dynamics using experimental data taken from in vivo experiments. Input data to the computational model were obtained in vivo one month after AVS creation; adjacent vessels were submitted to histological and mechanical examination. The 3-D shunt geometry was determined using biplane angiography. Ultrasound measurements of flow rates were performed with perivascular flow probes and pressures were recorded through intravascular catheters. These data were considered as boundary conditions for calculation of the unsteady flow field. Numerical findings are suggestive of strong Dean vortices toward both vein flow exits, verified by color Doppler. The high wall shear stresses (WSSs) and their gradients appear to be related to areas of IH and vessel wall stiffening, as evidenced in preliminary histological and mechanical studies of the venous wall. Additionally, suture line hyperplasia seems to be aggravated by the high WSS gradients noted at the transition line from graft to vein. PMID- 20350848 TI - A contrast function for independent component analysis without permutation ambiguity. AB - This brief deals with the problem of blind source separation (BSS) via independent component analysis (ICA). We prove that a linear combination of the separator output fourth-order marginal cumulants (kurtoses) is a valid contrast function for ICA under prewhitening if the weights have the same sign as the source kurtoses. If, in addition, the source kurtoses are different and so are the linear combination weights, the contrast eliminates the permutation ambiguity typical to ICA, as the estimated sources are sorted at the separator output according to their kurtosis values in the same order as the weights. If the weights equal the source kurtoses, the contrast is a cumulant matching criterion based on the maximum-likelihood principle. The contrast can be maximized by means of a cost-efficient Jacobi-type pairwise iteration. In the real-valued two-signal case, the asymptotic variance of the resulting Givens angle estimator is determined in closed form, leading to the contrast weights with optimal finite sample performance. A fully blind solution can be implemented by computing the optimum weights from the initial source estimates obtained by a classical ICA stage. An experimental study validates the features of the proposed technique and shows its superior performance compared to related previous methods. PMID- 20350849 TI - A convolutional learning system for object classification in 3-D Lidar data. AB - In this brief, a convolutional learning system for classification of segmented objects represented in 3-D as point clouds of laser reflections is proposed. Several novelties are discussed: (1) extension of the existing convolutional neural network (CNN) framework to direct processing of 3-D data in a multiview setting which may be helpful for rotation-invariant consideration, (2) improvement of CNN training effectiveness by employing a stochastic meta-descent (SMD) method, and (3) combination of unsupervised and supervised training for enhanced performance of CNN. CNN performance is illustrated on a two-class data set of objects in a segmented outdoor environment. PMID- 20350850 TI - A multiresolution approach to iterative reconstruction algorithms in X-ray computed tomography. AB - In computed tomography, the application of iterative reconstruction methods in practical situations is impeded by their high computational demands. Especially in high resolution X-ray computed tomography, where reconstruction volumes contain a high number of volume elements (several giga voxels), this computational burden prevents their actual breakthrough. Besides the large amount of calculations, iterative algorithms require the entire volume to be kept in memory during reconstruction, which quickly becomes cumbersome for large data sets. To overcome this obstacle, we present a novel multiresolution reconstruction, which greatly reduces the required amount of memory without significantly affecting the reconstructed image quality. It is shown that, combined with an efficient implementation on a graphical processing unit, the multiresolution approach enables the application of iterative algorithms in the reconstruction of large volumes at an acceptable speed using only limited resources. PMID- 20350852 TI - Generalized assorted pixel camera: postcapture control of resolution, dynamic range, and spectrum. AB - We propose the concept of a generalized assorted pixel (GAP) camera, which enables the user to capture a single image of a scene and, after the fact, control the tradeoff between spatial resolution, dynamic range and spectral detail. The GAP camera uses a complex array (or mosaic) of color filters. A major problem with using such an array is that the captured image is severely under sampled for at least some of the filter types. This leads to reconstructed images with strong aliasing. We make four contributions in this paper: 1) we present a comprehensive optimization method to arrive at the spatial and spectral layout of the color filter array of a GAP camera. 2) We develop a novel algorithm for reconstructing the under-sampled channels of the image while minimizing aliasing artifacts. 3) We demonstrate how the user can capture a single image and then control the tradeoff of spatial resolution to generate a variety of images, including monochrome, high dynamic range (HDR) monochrome, RGB, HDR RGB, and multispectral images. 4) Finally, the performance of our GAP camera has been verified using extensive simulations that use multispectral images of real world scenes. A large database of these multispectral images has been made available at http://www1.cs.columbia.edu/CAVE/projects/gap_camera/ for use by the research community. PMID- 20350851 TI - Fast space-variant elliptical filtering using box splines. AB - The efficient realization of linear space-variant (non-convolution) filters is a challenging computational problem in image processing. In this paper, we demonstrate that it is possible to filter an image with a Gaussian-like elliptic window of varying size, elongation and orientation using a fixed number of computations per pixel. The associated algorithm, which is based upon a family of smooth compactly supported piecewise polynomials, the radially-uniform box splines, is realized using preintegration and local finite-differences. The radially-uniform box splines are constructed through the repeated convolution of a fixed number of box distributions, which have been suitably scaled and distributed radially in an uniform fashion. The attractive features of these box splines are their asymptotic behavior, their simple covariance structure, and their quasi-separability. They converge to Gaussians with the increase of their order, and are used to approximate anisotropic Gaussians of varying covariance simply by controlling the scales of the constituent box distributions. Based upon the second feature, we develop a technique for continuously controlling the size, elongation and orientation of these Gaussian-like functions. Finally, the quasi separable structure, along with a certain scaling property of box distributions, is used to efficiently realize the associated space-variant elliptical filtering, which requires O(1) computations per pixel irrespective of the shape and size of the filter. PMID- 20350853 TI - Exploiting transitivity of correlation for fast template matching. AB - Elimination Algorithms are often used in template matching to provide a significant speed-up by skipping portions of the computation while guaranteeing the same best-match location as exhaustive search. In this work, we develop elimination algorithms for correlation-based match measures by exploiting the transitivity of correlation. We show that transitive bounds can result in a high computational speed-up if strong autocorrelation is present in the dataset. Generally strong intrareference local autocorrelation is found in natural images, strong inter-reference autocorrelation is found if objects are to be tracked across consecutive video frames and strong intertemplate autocorrelation is found if consecutive video frames are to be matched with a reference image. For each of these cases, the transitive bounds can be adapted to result in an efficient elimination algorithm. The proposed elimination algorithms are exact, that is, they guarantee to yield the same peak location as exhaustive search over the entire solution space. While the speed-up obtained is data dependent, we show empirical results of up to an order of magnitude faster computation as compared to the currently used efficient algorithms on a variety of datasets. PMID- 20350855 TI - Detection and restoration of defective lines in the SPOT 4 SWIR band. AB - This paper presents the categorization and restoration of defective lines developed in pushbroom images. About 100 of the 3000 SPOT 4 SWIR detectors malfunction, which degrades image quality. Conventional methods have difficulties in effectively detecting and restoring defective lines, because they ignore the heterogeneity of the ground surface and the presence of sporadically unstable detectors with gain and offset that vary during a scan. While all defective lines have previously been considered as a single type, here they are categorized into three types according to the variation pattern in the scanning direction: constant defective lines, irregular defective lines, and irrecoverable defective lines. The detection procedure utilizes summed data and standard deviation data that consist of abnormal peaks originating from defective lines and a slowly varying baseline reflecting the surface characteristics within the image. The defective lines are detected by finding abnormal peaks, and classified and restored by using either a moment-matching method or interpolation, depending upon their types. Three SPOT 4 images were used to test and evaluate the performance of the proposed method. From the test results, the constant defective line was the most common type, comprising about 60%, while the irregular defective lines caused serious image degradation because of the difficulty of detecting and classifying them. Commission and omission errors were less than 10% and detection accuracy was higher than 90%. The analysis of signal-to-noise ratio (SNR) showed that the low SNR created by the defective lines was effectively removed. Our method gave a significant improvement of the detection and restoration capability. PMID- 20350854 TI - On the convergence of planar curves under smoothing. AB - Curve smoothing has two important applications in computer vision and image processing: 1) the curvature scale-space (CSS) technique for shape analysis, and 2) the Gaussian filter for noise suppression. In this paper, we study how planar curves converge as they are smoothed with increasing scales. First, two types of convergence behavior are clarified. The coined term shrinkage refers to the reduction of arc-length of a smoothed planar curve, which describes the convergence of the curve latitudinally; and another coined term collapse refers to the movement of each point to its limiting position, which describes the convergence of the curve longitudinally. A systematic study on the shrinkage and collapse of three categories of curve models is then presented. The corner models helps to reveal how the local structures of planar curves collapse and what the smoothed curves may converge to. The sawtooth models allows us to gain insights regarding how noise is suppressed from noisy planar curves by the Gaussian filter. Our investigation on the closed curves shows that each curve collapses to a point at its center of mass. However, different curves may yield different limiting shapes at the infinity scale. Finally, based upon the derived results the performance of the CSS technique in corner detection and shape representation is analyzed, and a fast implementation method of the Gaussian filter for noise suppression is proposed. PMID- 20350856 TI - Orientation modulation for data hiding in clustered-dot halftone prints. AB - We present a new framework for data hiding in images printed with clustered dot halftones. Our application scenario, like other hardcopy embedding methods, encounters fundamental challenges due to extreme bilevel quantization inherent in halftoning, the stringent requirements of image fidelity, and other unavoidable printing and scanning distortions. To overcome these challenges, while still allowing for automated extraction of the embedded data and a high embedding capacity, we propose a number of innovations. First, we perform the embedding jointly with the halftoning by employing an analytical halftone threshold function that allows steering of the halftone spot orientation within each halftone cell based upon embedded data. In this process, image fidelity is emphasized and, if necessary, the capability to recover individual data values is sacrificed resulting in unavoidable erasures and errors. To overcome these and other sources of errors, we propose a suitable data detection and error control methodology based upon a statistical representation for the print-scan channel that effectively models the channel dependence upon the cover image gray-level. To combat the geometric distortion inherent in the print-scan process, we exploit the periodic halftone structure to recover from global scaling and rotation and propose a novel decision directed synchronization technique that counters locally varying printing distortion. Experimental results demonstrate the power of the proposed framework: we achieve high operational rates while preserving halftone image quality. PMID- 20350857 TI - Camera scheduling and energy allocation for lifetime maximization in user-centric visual sensor networks. AB - We explore camera scheduling and energy allocation strategies for lifetime optimization in image sensor networks. For the application scenarios that we consider, visual coverage over a monitored region is obtained by deploying wireless, battery-powered image sensors. Each sensor camera provides coverage over a part of the monitored region and a central processor coordinates the sensors in order to gather required visual data. For the purpose of maximizing the network operational lifetime, we consider two problems in this setting: a) camera scheduling, i.e., the selection, among available possibilities, of a set of cameras providing the desired coverage at each time instance, and b) energy allocation, i.e., the distribution of total available energy between the camera sensor nodes. We model the network lifetime as a stochastic random variable that depends upon the coverage geometry for the sensors and the distribution of data requests over the monitored region, two key characteristics that distinguish our problem from other wireless sensor network applications. By suitably abstracting this model of network lifetime and utilizing asymptotic analysis, we propose lifetime-maximizing camera scheduling and energy allocation strategies. The effectiveness of the proposed camera scheduling and energy allocation strategies is validated by simulations. PMID- 20350858 TI - Coding order decision of B frames for rate-distortion performance improvement in single-view video and multiview video coding. AB - The coding gain that can be achieved by improving the coding order of B frames in the H.264/AVC standard is investigated in this work. We first represent the coding order of B frames and their reference frames with a binary tree. We then formulate a recursive equation to find out the binary tree that provides a suboptimal, but very efficient, coding order. The recursive equation is efficiently solved using a dynamic programming method. Furthermore, we extend the coding order improvement technique to the case of multiview video sequences, in which the quadtree representation is used instead of the binary tree representation. Simulation results demonstrate that the proposed algorithm provides significantly better R-D performance than conventional prediction structures. PMID- 20350859 TI - Recognition of affect based on gait patterns. AB - To provide a means for recognition of affect from a distance, this paper analyzes the capability of gait to reveal a person's affective state. We address interindividual versus person-dependent recognition, recognition based on discrete affective states versus recognition based on affective dimensions, and efficient feature extraction with respect to affect. Principal component analysis (PCA), kernel PCA, linear discriminant analysis, and general discriminant analysis are compared to either reduce temporal information in gait or extract relevant features for classification. Although expression of affect in gait is covered by the primary task of locomotion, person-dependent recognition of motion capture data reaches 95% accuracy based on the observation of a single stride. In particular, different levels of arousal and dominance are suitable for being recognized in gait. It is concluded that gait can be used as an additional modality for the recognition of affect. Application scenarios include monitoring in high-security areas, human-robot interaction, and cognitive home environments. PMID- 20350860 TI - Reinforcement learning for partially observable dynamic processes: adaptive dynamic programming using measured output data. AB - Approximate dynamic programming (ADP) is a class of reinforcement learning methods that have shown their importance in a variety of applications, including feedback control of dynamical systems. ADP generally requires full information about the system internal states, which is usually not available in practical situations. In this paper, we show how to implement ADP methods using only measured input/output data from the system. Linear dynamical systems with deterministic behavior are considered herein, which are systems of great interest in the control system community. In control system theory, these types of methods are referred to as output feedback (OPFB). The stochastic equivalent of the systems dealt with in this paper is a class of partially observable Markov decision processes. We develop both policy iteration and value iteration algorithms that converge to an optimal controller that requires only OPFB. It is shown that, similar to Q -learning, the new methods have the important advantage that knowledge of the system dynamics is not needed for the implementation of these learning algorithms or for the OPFB control. Only the order of the system, as well as an upper bound on its "observability index," must be known. The learned OPFB controller is in the form of a polynomial autoregressive moving average controller that has equivalent performance with the optimal state variable feedback gain. PMID- 20350861 TI - [Relation between Shistosoma mansoni and hepatosplenomegalies]. AB - INTRODUCTION: Although they remain a neglected transmissible disease, affecting mainly people in poor countries, the combined forms of schistosomiasis are second only to malaria as a major parasitic disease. Although both urinary and intestinal schistosomiasis are endemic in Madagascar, this study focuses only on the intestinal forms. The symptoms may remain unnoticed or be ignored, for the seriousness of intestinal schistosomiasis is due mainly to its hepatosplenic complications. OBJECTIVES: To estimate the etiological fraction of Schistosoma mansoni involved in hepatomegaly (HM), splenomegaly (SM) and hepatosplenomegaly (HSM), with or without signs of portal hypertension (PHT). METHODS: This file based retrospective study includes patients admitted to the University Hospital of Antananarivo, Madagascar, between January 2005 and July 2008, who presented with HM, SM, HSM and/or PHT. The case was attributed to schistosomiasis if blood serology, tested with ELISA, was positive for this parasite. The statistical analysis used three approaches: a cross-sectional approach, a longitudinal approach (retrospective cohort), and a "case-control" approach. RESULTS: Of 7308 admissions during this period, 269 (4%) were diagnosed with a hepatosplenic complication and were retained. The average age (+/- standard deviation) was 47.8 (+/- 16.4) years. HM accounted for 55.4% of cases, SM 18.9%, HTP 18.6% and HSM 18.6%. Serology was positive for schistosomiasis in 21.6% of cases. The sex ratio (men:women) for these cases was 1.9, and 67.3% of the patients were aged 30 years or older. The main schistosomiasis complications were SM (n=22) and HTP (n=22). The age group most affected depended on the specific complication: for HM, 28.6% of patients were aged between 40 and 49 years; for HSM, 57.1% were aged between 30 and 40 years. The prevalence of SM was lower in subjects between 50 and 59 years of age (4.5%) than the other complications. Patients with positive serology results were significantly younger than those with negative results, or whose serology was not checked (37.8 years vs. 50.5 years, p < 0.001). Stratification according to complication showed that the etiological fraction of schistosomiasis was 76% for patients with SM, 79% for HTP, 58% for HSM and 4.9% for HM. The retrospective cohort and the case-control analyses both showed that a history of dysentery and frequent contact with water were the main factors associated with complicated schistosomiasis. It is important to note that urban and rural residents had the same risk of developing schistosomiasis with complications (OR: 0.9 [0.4; 1.9]). CONCLUSION: This study showed that schistosomiasis infection is strongly associated with hepatosplenic pathologies. One of the shortcomings of the study is the absence of any analysis of the course and outcome in the study patients. Nevertheless, the course of oesophageal varices, SM or HSM in patients with HTP indicates that schistosomiasis was often fatal. PMID- 20350863 TI - [Treatment possibilities in breast cancer progressing after anthracyclines and/or taxanes]. AB - The treatment of recurrent, progressing, metastatic breast cancer, which has previously been exposed to anthracyclines and/or taxanes is not only a major clinical challenge, but has a significant social impact too. In the absence of formal guidelines, this review has aimed to summarize the published evidence that is needed to guide clinical decision-making. Four new agents are approved for use in this setting: capecitabine, gemcitabine, ixabepilone, and nanoparticle albumin bound paclitaxel. Nevertheless this review summarizes the results of studies with other active agents, as liposomal doxorubicin, rotation of taxanes, larotaxel, vinorelbine, and other biological agents. PMID- 20350864 TI - [Comparison of breast cancer in young and old women based on clinicopathological features]. AB - The two far ends of the age at the diagnosis of breast cancer are the age of younger than 35, and that of older than 70. Most probably, these two groups of patients differ in many ways. The aim of our present study was to underline the fact that age at the diagnosis of breast cancer is indeed a prognostic factor. Between October 1995 and March 2009, 80 old and 51 young breast cancer patients were treated at the Department of Diagnostic Radiology and Oncotherapy, Semmelweis University, Budapest. The prognostic and predictive factors of the tumors were analysed together with the disease-free and overall survival data. There were statistically significant differences between the two groups concerning the menstrual and reproductive factors, histological characteristics and immunophenotype of the tumors. Tumor size, nodal status and the Nottingham Prognostic Index did not show statistically significant differences. A trend to a shorter disease-free survival, higher rate of distant metastases and disease specific death was seen in the group of young patients, but it was not significant. Overall survival was significantly shorter in the group of young patients. Therefore, we can state that young patients have a more aggressive disease and worse outcome. There is an increased importance of self examination in these groups, since both age groups are beyond the age limits of the screening population in Hungary. The media and primary school education as well should be involved in educating women concerning this aspect. The individual follow-up of young patients with positive family history should also be established. PMID- 20350865 TI - [Health-economics of oncology care: changes in hospital bed capacity]. AB - The aim of our study was to analyze the effect of hospital bed reforms on April 1, 2007 in Hungary, with special respect to the changes of acute care cancer beds. Data were derived from the database of the National Health Insurance Fund Administration (OEP). We identified cancer care hospital capacities (beds) with the following financial codes: code nr. 12 (oncology), code nr. 24 (radiotherapy) and code nr. 28 (hematology). We analyzed the changes of these beds before and after the reform. The total number of acute care hospital beds decreased by 25.7%, while in the field of cancer care beds we found different trends. The number of hospital beds for oncology care and hematology care decreased by 11.4% and 11.1%, respectively. The number of hospital beds for radiotherapy departments even increased by 16.3%. We did not find any changes in regional inequalities. We can conclude that during the hospital bed reform in 2007, the number of oncology and hematology care beds decreased less than the total number of acute care hospital beds, and the number of beds for radiotherapy even increased, without significantly affecting the regional inequalities. PMID- 20350866 TI - [Health economics of oncology care: financial effect of performance volume limit (PVL)]. AB - The aim of our study is to analyze the effect of performance volume limit (PVL) on the performance indicators of acute oncology care, with special respect to the health insurance reimbursement not paid to health care providers. Data were derived from the nationwide administrative dataset of the National Health Insurance Fund Administration (OEP) covering the period of 2006-2008. We analyzed the effect of PVL according to medical specialities. We calculated the average annual reimbursement rate of DRG cost-weight with and without the application of PVL. The loss due to PVL was calculated both by monetary terms and as the % of annual revenue. The loss of medical specialities measured by monetary units (Hungarian forint, HUF) and as a percent of their revenues was the following in 2008: oncology 1327 million HUF (4.7%), cardiology 791 million HUF (3.0%), gynecology and obstetrics 772 million HUF (3.0%), internal medicine 708 million HUF (3.3%), intensive care 661 million HUF (2.5%), surgery 637 million HUF (3.2%), pediatrics 614 million HUF (3.9%), traumatology 545 million HUF (2.5%), radiotherapy 438 million HUF (3.1%). The application of performance volume limit had significantly different effect on the different medical specialities. Oncology care can be considered as one of the largest losers of the application of performance volume limit. PMID- 20350867 TI - [Effect of lifestyle counseling given by health personnel on the changes in dietary habits of Hungarian women treated for cancer]. AB - The aim of this study was to investigate the changes in dietary habits in women with gynecological or breast cancer, and to analyze the role of some demographic factors, type of the malignant tumor, and the role of medical staff's advice in dietary behavior change of these women, after the diagnosis of cancer. A self administered questionnaire-based retrospective study was performed, and 155 randomly selected patients, treated for gynecological or breast cancer, were involved. A self-developed questionnaire was used to measure the socio demographic characteristics, the circumstances of visiting the physician, therapy, present health status and lifestyle before and after the diagnosis of neoplasm. More than three-fourths of the women reported changes in nutrition after the diagnosis of cancer. The consumption of fruits and vegetables increased in the highest proportion (70.3%). Women with higher education changed their diet in higher proportion (p=0.031) compared to women with lower education. Women who were advised to change their lifestyle by their therapists were about four times more likely (OR: 3.87; CI: 1.40-10.69 ) to change their nutrition. Patients with breast cancer changed three times more likely (OR: 3.21; CI: 1.05-9.84) their dietary habits than patients with gynecological cancer. The most influential proven factor to make cancer patients alter their diet was being advised for this by physicians. Thus, our study proved that physicians and nurses have a very important role in changing their cancer patients' nutritional habits into a healthier one. PMID- 20350868 TI - [Host defense peptides and peptidomimetics as new weapons for cancer treatment]. AB - Host defence peptides (HDP) produced by almost all species of living organisms and widely recognized as antimicrobial antibiotics have also proved to be capable of killing a wide variety of cancer cells. In this respect they have many advantages over conventional cytotoxic chemotherapeutic agents. They seem to kill cancer cells by effects on plasma membranes and/or the membranes of mitochondria. They are often effective against multidrug-resistant cells. They have a broad spectrum of activity in that their killing effects are not restricted to particular kinds of cancer. Above all they commonly have few side effects in that they do not have the same detrimental effects on normal cells as they do on cancer cells. It has been demonstrated that HDP can be used as effective adjuvants to conventional chemotherapeutic agents. In addition they have effects on neo-angiogenesis which is important in relation to tumour growth. HDP have been shown to be powerful immunomodulators in a number of circumstances and in this respect they are believed to be instrumental in strengthening immunological host defence against cancer cells. Importantly it has also been shown that certain HDP have the capability to alter the capacity of cells to import Ca ions by affecting the location and thus function of calreticulin. Such changes it has been argued are significant in facilitating the killing of tumour cells by immunogical means. HDP constitute a novel class of anticancer agents for which, as we develop better knowledge of their pharmacokinetic profiles and learn better how to tailor their administration, hold high promise to augment or even replace the currently available cytotoxic anticancer chemotherapeutic agents most of which owe their efficacy to their capacity to bind to and damage target cell DNA. PMID- 20350869 TI - [Molecular basis of bone metastasis formation and its targeted therapy]. AB - Formation of bone metastasis is a hallmark of the progression of several solid cancers, providing example for the organ specificity of the process. Bone metastasis may result in both venous and arterial dissemination. Though the molecular basis of the lytic and plastic bone metastasis formation is different, in reality these organ metastases represent a mixture of the two processes. The basis of bone metastasis formation is the activation of osteoclasts and the resulting bone resorption, initiating a vicious circle by activating the initiator cancer cell. The discovery of osteoclast-bone matrix interaction inhibitor bisphosphonates revolutionized the therapy of bone metastasis. Clarifying the molecular pathways involved in bone metastasis formation identified osteoclast differentiation as another feasible target. This process is under control of the TNF receptor family member RANK and its ligand RANKL. The feasibility of using this system to control bone resorption or cancer-induced skeletal events was proven clinically in trials using an anti-RANKL antibody. The clinical success of anti-RANKL antibody therapy provide further evidence that only precise identification of molecular pathways operational in cancers can lead to discovery of more effective (targeted) therapies. PMID- 20350875 TI - Pneumococcal conjugate vaccines in the prevention of childhood pneumonia. AB - Lower respiratory tract infections are among the most important causes of childhood mortality worldwide, more than 2 million children die due to pneumonia every year. A number of infections caused by the main pathogens related to pneumonia can be prevented through vaccination ( S. pneumoniae, H. influenzae type-b, morbilli, pertussis, influenza). In the last decade, after the introduction of the 7-valent pneumococcal conjugated vaccine (PCV), the epidemiological background of childhood pneumonia has changed. Recently, several studies have been performed to collect data and evidences about the efficacy of PCV against noninvasive pneumococcal diseases (e.g. pneumonia, otitis media). These investigations showed 10-50% decrease of all pneumonia cases, 10-30% decrease of radiologically diagnosed pneumonia, and 50-70% decrease of the incidence of pneumococcal pneumonia in children. The aim of this review was to determine the role of the PCV in the prevention of childhood pneumonia according to the medical literature, and to summarize the efforts of global organizations (WHO, UNICEF, GAVI) in the fight against pneumonia in children. PMID- 20350876 TI - Inhibitory effects of Fortunella japonica var. margarita and Citrus sunki essential oils on nitric oxide production and skin pathogens. AB - A number of essential oils from citrus peels are claimed to have biological activities. Citrus peel, called 'Jin-Pi', is used in traditional medicine for digestion, severe cold, and fever. However, the antibacterial activities against skin pathogens and anti-inflammatory effects of the essential oils of Citrus sunki (JinGyul) and Fortunella japonica var. margarita (GumGyul) have not yet been described. Therefore, in this study, the essential oils of the citrus species C. sunki (CSE) and F. japonica var. margarita (FJE), both native to the island of Jeju, Korea, were examined for their anti-inflammatory and antimicrobial activities against skin pathogens. Four human skin pathogenic microorganisms, Staphylococcus epidermidis CCARM 3709, Propionibacterium acnes CCARM 0081, Malassezia furfur KCCM 12679, and Candida albicans KCCM 11282, were studied. CSE and FJE exhibited strong antimicrobial activity against most of the pathogenic bacteria and yeast strains that were tested. Interestingly, CSE and FJE even showed antimicrobial activity against antibiotic-resistant S. epidermidis CCARM 3710, S. epidermidis CCARM 3711, P. acnes CCARM9009, and P. acnes CCARM9010 strains. In addition, CSE and FJE reduced the lipopolysaccharide (LPS)-induced secretion of nitric oxide (NO) in RAW 264.7 cells, indicating that they have anti-inflammatory effects. We also analysed the chemical composition of the oils by gas chromatography-mass spectrometry (GC-MS) and identified several major components, including dl-limonene (68.18%) and beta-myrcene (4.36%) for CSE, and dl-limonene (61.58%) and carvone (6.36%) for FJE. Taken together, these findings indicate that CSE and FJE have great potential to be used in human skin health applications. PMID- 20350877 TI - Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients. AB - Liver fibrosis (LF), where the chronic HCV infection is a major cause, is a characteristic of chronic liver diseases. LF results from chronic damage to the liver in conjunction with the accumulation of ECM proteins. Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are thought to play an essential role in the hepatic lesions. The available data concerning the circulating levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in chronic hepatitis C are not conclusive. Therefore, the present study was designed to seek the relationship between serum MMP-9, and TIMP-1 to liver status in chronic liver disease in fifty patients divided into three groups (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma). MMP-9 and TIMP-1 were analyzed by the enzyme linked immunosorbent assay (ELISA). The results showed that the lowest serum level of MMP-9 was found in chronic hepatitis patients compared to the control ( P < 0.05). Serum MMP-9 is decreasing during progression of chronic hepatitis to cirrhosis showing the least level in the cirrhotic group. Serum TIMP-1 was significantly higher in the cirrhotic group compared to chronic hepatitis ( P < 0.05) and controls ( P < 0.001). MMP-9 was negatively correlated to both TIMP-1 and the histological severity in chronic hepatitis. There was a positive correlation between TIMP-1 and the degree of fibrosis (r = 0.73, P < 0.001). Lastly, there was a statistically significant increase of MMP-9 ( P < 0.001) and TIMP-1 ( P < 0.05) in HCC patients compared with the other groups. In conclusion, these findings raise the possibility of using serum TIMP-1 as a non-invasive assay in liver fibrosis. Further, the altered balance between circulating MMP-9 and TIMP-1 during HCV infection may play an important role in aggravating liver injury progression in chronic liver diseases. PMID- 20350878 TI - Investigation of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae outbreaks in Hungary between 2005 and 2008. AB - Fourteen outbreaks in Hungary between 2005 and 2008 caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) were epidemiologically investigated and the isolated pathogens were characterized by molecular techniques. Ten of the fourteen outbreaks occurred in adult wards and four in neonatal units affecting a total number of 73 patients. The 54% [40] of the patients developed bloodstream infections and 21.9%-21.9% [16] pneumonia and surgical site infections, respectively. The overall rate of mortality proved high: 36.9% [27]. Outbreaks in adults affected more patients, had higher attack rates, were more prolonged in duration and had a 6.9-fold higher mortality rate than outbreaks observed in neonates. The outbreaks in neonates were caused by SHV type ESBL-producing klebsiellae, while in the "adult outbreaks" exclusively CTX-M type ESBL-KP strains were involved. While the outbreak strains isolated from neonatal units could be assigned to a variety of pulsotypes, the previously described K. pneumoniae epidemic clones, ST15 and ST147, could be identified among the pathogens causing outbreaks in adult units. PMID- 20350879 TI - Monitoring of drug resistance in therapy-naive HIV infected patients and detection of African HIV subtypes in Hungary. AB - Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naive Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). On the contrary, 25% of viruses transmitted by homosexual activity contained mutations led to resistance to NNRT. Viruses from 11 percent of cases were resistant to 2 classes of inhibitors, and 7 percent to three classes of inhibitors. Based upon sequence data non-B subtypes and CRFs were detected in more than 71% of cases. HIV-1 C (10.7%), HIV-F1 (7.2%) and HIV-1 G (3.6%) were detected as the more frequent subtypes. Among the HIV-1 recombinant viruses CRF02_AG variants were found more frequently (28.5%) followed by CRF06_cpx (17.8%) indicating penetration of non-B subtypes and recombinant African variants into Hungary, which raises serious clinical and public health consequences. PMID- 20350880 TI - Prevention of tinea pedis and onychomycosis: a view from Russia. PMID- 20350882 TI - Infusion reactions: diagnosis, assessment, and management. AB - Many cancer therapies administered by IV infusion, including monoclonal antibodies, have the potential for infusion reactions. All infusion reactions involve the immune system; however, some (anaphylactic) are allergic in nature and usually are mediated by immunoglobulin E (lgE), whereas others (anaphylactoid) are not true allergic reactions and are not mediated by lgE. Although reactions can be allergic or nonallergic, the clinical manifestations are the same and require prompt, accurate assessment and astute management to avoid severe adverse events, including fatality. Monoclonal antibodies have a unique side-effect profile that includes the potential for nonallergic infusion reactions caused by cytokine release. Understanding the pathophysiology underlying any infusion reaction will enhance decision making regarding rechallenge and thereby improve treatment outcomes. Rituximab is an example of a drug with the potential for varying types of infusion reactions. This article discusses oncology nurses' role in patient risk assessment, institution of prophylactic measures, administration monitoring, severity grading, management, and follow-up. This understanding will clarify new data regarding the safety of a rapid infusion schedule of rituximab. PMID- 20350883 TI - Mammography and the media. PMID- 20350884 TI - The window watcher. PMID- 20350885 TI - Oncology nurses must join tobacco-control efforts. PMID- 20350886 TI - Survivorship care for adult recipients of hematopoietic cell transplantations. AB - Survivors of hematopoietic cell transplantation have undergone aggressive treatments and experience significant life-altering events. Survivorship care plans can address such issues. PMID- 20350887 TI - The Coombs test. AB - The Coombs test, established as a clinical tool in 1945 by R.R. Coombs, usually is ordered when hemolytic anemia is suspected or if a transfusion reaction has occurred. An overview of the etiologies of these two conditions will increase oncology nurses' understanding of what is measured with a Coombs test and increase the understandings of why a Coombs test is ordered, what diagnosis is suspected, and what patient populations are at highest risk for transfusion reactions. PMID- 20350888 TI - Back pain caused by a solitary plasmacytoma of bone. AB - This article presents initial diagnostic workup and criteria for diagnosing solitary plasmacytoma of bone (SPB) versus multiple myeloma. The authors discuss the incorporation of current imaging technologies into the diagnosis and staging of SPB and multiple myeloma. In addition, the article addresses treatment modalities and discusses the importance of oncology nurses' awareness of this rare condition. PMID- 20350889 TI - Living and dying in East Africa: implementing the End-of-Life Nursing Education Consortium curriculum in Tanzania. AB - Education about palliative care is crucial for oncology nurses, particularly in the developing world, where most patients present with advanced disease and heavy symptom burden. The End-of-Life Nursing Education Consortium-International training program was implemented in Tanzania to provide nurses with the knowledge, expertise, and tools to better care for the dying and to educate others. The curriculum was presented to 39 participants over three days, including didactic presentations, small group discussions, and role play. None of the participants had received previous formal palliative care training. The participants rated their impression of the course as excellent. Follow-up at eight months yielded similar findings regarding the effectiveness of the curriculum. International education regarding palliative care for those with cancer requires an understanding of different disease patterns and clinical practices, along with cultural humility and empathy. These experiences are extraordinarily enriching, giving nurses a unique perspective on palliative care that ultimately informs their own practice. PMID- 20350890 TI - Providing palliative care in the ambulatory care setting. AB - Palliative care that provides specialized attention to pain and symptom management is important for patients with cancer. Palliative care aims to reduce pain and other symptoms through an interdisciplinary approach involving physicians, nurses, social workers, and other members of the healthcare team. Families are included in care planning. Patients and families benefit from the availability of palliative care services early in the disease process, particularly when symptoms impact quality of life. One way to implement early palliative interventions is the establishment of an ambulatory care clinic dedicated to palliative care. This article describes the experience of an outpatient palliative care clinic at a large teaching hospital by using case studies to highlight the benefits of ambulatory palliative care and concluding with recommendations for research. PMID- 20350891 TI - Helping patients with cancer prepare for hospice. AB - People with life-limiting cancer will make decisions about their end-of-life (EOL) care at some point during their illness. Hospice is an option of care aimed at providing optimal quality of life at EOL. Nursing plays a major role in helping people transition from curative treatments or treatments that control the disease to EOL care. Choosing hospice is difficult for many patients with cancer. In addition, healthcare providers also face challenges in discussing EOL care. This article explores issues pertaining to EOL care conversations between nurses and patients and offers strategies that can be implemented by nurses to aid patients' transition to hospice care. PMID- 20350892 TI - Androgen-deprivation bone loss in patients with prostate cancer. AB - An increasing number of men with prostate cancer being treated with androgen deprivation therapy (ADT) are at increased risk for developing osteoporosis. Osteoporosis often is overlooked in men and can have significant adverse economic effects and reduce quality of life, particularly if a fracture occurs. Nurses play a major role in identifying men who are at risk because of lifestyle factors and ADT. Men receiving ADT should undergo regular screening with bone densitometry to detect osteoporosis and monitor the effectiveness of therapy. Nurses also have a major role in administering medications to promote bone health. Many implications exist for patient education related to bone health in men. PMID- 20350893 TI - Developing a high-dose-rate prostate brachytherapy program. AB - This article provides oncology nurses with an overview of high-dose-rate brachytherapy for the treatment of prostate cancer. Many treatment options are available for men diagnosed with prostate cancer. Oncology nurses must know about this potential treatment option so they can provide appropriate education, support, and self-care management advice. Program requirements, patient eligibility, and essential planning recommendations are discussed. PMID- 20350894 TI - The impact of methods of information on chemotherapy-related side effects. AB - A systematic review of the literature regarding the effectiveness of various methods of information given to patients with cancer receiving chemotherapy education revealed that psycho-educational interventions minimized the intensity and impact of treatment-related fatigue on daily life in the short term for patients undergoing chemotherapy. Studies that investigated efficacy of interactive multimedia devices revealed no statistical improvement in information recall, quantity of self-care activities, and fatigue levels between groups. Three of the multimedia studies focused on anxiety and depression trends before and during treatment, with mixed results. Several studies revealed no significant difference in either anxiety or depression. Others concluded that patients who viewed video information in conjunction with standard care were less anxious and depressed. Combined, these studies revealed that multimedia devices did not improve recall of information and that psycho-educational interventions were able to improve the impact of treatment-related side effects, namely fatigue, in the short term. This suggests that the educational needs of patients with cancer require a complex series of factors that impact the individual's ability to understand how and when to initiate recommended self-care strategies. PMID- 20350895 TI - Mobilization of hematopoietic stem cells for use in autologous transplantation. AB - Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow. HSCs are capable of self-renewal and give rise to progenitor cells, multipotent cells that differentiate and proliferate into the mature cells of the blood and immune system. HSCs and progenitor cells are released from the bone marrow into the peripheral blood through a process called mobilization. HSCs then are collected from the blood in a process called apheresis and cryopreserved for administration following the high-dose preparative regimen. This article reviews stem cell biology, current mobilization strategies, use of novel mobilization agents, and nursing care of patients during the mobilization phase of autologous HSCT. Understanding the biology and process of HSC mobilization is critical for transplantation nurses to deliver and coordinate care during this complex phase of autologous HSCT. PMID- 20350896 TI - Lapatinib side-effect management. AB - Lapatinib is an oral dual tyrosine kinase inhibitor targeting epidermal growth factor receptor and HER2. Diarrhea and dermatologic adverse events are reported commonly by patients treated with lapatinib. Diarrhea can range from mild to severe based on the agents used in combination with lapatinib. The adverse events may diminish quality of life, reduce treatment adherence, and lead to discontinuation of therapy. Consequently, proactive management of diarrhea is crucial, especially in patients receiving lapatinib in combination with other agents that also cause diarrhea. As the utility of lapatinib expands, crucial proactive diarrhea-management and dose-reduction strategies are evolving to decrease the likelihood of grade 3 or 4 toxicity. With regard to dermatologic adverse events, most are mild to moderate in severity, are of limited duration, and frequently do not require treatment intervention. However, in some patients, management of dermatologic adverse events is of great importance. This article reviews data regarding diarrhea and dermatologic adverse events in patients treated with lapatinib and summarizes the key role that oncology nurses play in educating patients about the potential for adverse events and the importance of preventive measures, ongoing surveillance, appropriate treatment, and dose reductions. PMID- 20350897 TI - Safer vesicant administration: improving communication across provider lines. AB - The administration of vesicant drugs involves nurses and physicians as stakeholders in providing safe patient care. Improving communication often is the first step to increasing the awareness and problem-solving for the patient care team. PMID- 20350898 TI - The journey to Magnet: establishing a research infrastructure. AB - Developing and sustaining a research infrastructure that meets Magnet program requirements are daunting responsibilities. Our Lady of the Lake Regional Medical Center in Louisiana created the program director of nursing research position to coordinate the research council and ongoing projects. This article discusses the process of developing and improving a nursing research program. PMID- 20350899 TI - Fertility preservation: an option for women with cancer? AB - Many women of childbearing age are diagnosed with cancer in the United States each year. Improved survival rates can give many time to still have their own families if they choose. Although cancer treatments can dramatically increase survivorship, they also can negatively affect future fertility. Women newly diagnosed with cancer may not be aware of the possible damage to their future fertility as their main concern is survival. Women who may have their fertility compromised by cytotoxic treatments should be counseled and referred to reproductive specialists to explore their options. Although receiving a diagnosis of cancer is overwhelming, fertility counseling should be initiated as early as possible so that sufficient time exists to preserve fertility before ovarian damage occurs. Many fertility preservation options, including egg, embryo, and ovarian tissue freezing, can be done in a short period of time so as not to delay the start of cancer treatment. To educate and support women with cancer of childbearing age, oncology nurses should be aware of fertility preservation options and work closely with infertility nurses. PMID- 20350900 TI - Coding guidelines for continuous glucose monitoring. PMID- 20350901 TI - American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes. PMID- 20350902 TI - Thyroid hormone in childhood obesity--no "quick fix". PMID- 20350903 TI - Hypophysitis: it's not your mother's pituitary adenoma. PMID- 20350904 TI - W(h)ither metreleptin for lipodystrophy and the metabolic syndrome? PMID- 20350905 TI - American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Practice Guidelines--2010 update. AB - In 2004, the American Association of Clinical Endocrinologists (AACE) published the "Protocol for Standardized Production of Clinical Practice Guidelines," which was to be implemented in forthcoming clinical practice guidelines (CPG). This protocol formally incorporated subjective factors and evidence-based medicine (EBM) methods that tightly mapped evidence levels to recommendation grades. A uniform publication template and multilevel review process were also outlined. Seven CPG have been subsequently published with use of this 2004 AACE protocol. Recently, growing concerns about the usefulness of CPG have been raised. The purposes of this report are to address shortcomings of the 2004 AACE protocol and to present an updated 2010 AACE protocol for CPG development. AACE CPG are developed without any industry involvement. Multiplicities of interests among writers and reviewers that might compromise the usefulness of CPG are avoided. Three major goals are to (1) balance transparently the effect of rigid quantitative EBM methods with subjective factors, (2) create a less onerous, less time-consuming, and less costly CPG production process, and (3) introduce an electronic implementation component. The updated 2010 AACE protocol emphasizes "informed judgment" and hybridizes EBM descriptors (study design type), qualifiers (study flaws), and subjective factors (such as risk, cost, and relevance). In addition, by focusing on more specific topics and clinical questions, the expert evaluation and multilevel review process is more transparent and expeditious. Lastly, the final recommendations are linked to a new electronic implementation feature. PMID- 20350906 TI - Gastrointestinal side effects of bisphosphonates obscuring vascular disease. PMID- 20350907 TI - The glands of Owen. PMID- 20350908 TI - Saul Hertz, MD (1905-1950): a pioneer in the use of radioactive iodine. PMID- 20350912 TI - Impaired postoperative hyperglycemic stress response associated with increased mortality in patients in the cardiothoracic surgery intensive care unit. AB - OBJECTIVE: To describe the association of tight glycemic control with intensive insulin therapy and clinical outcome among patients in the cardiothoracic surgery intensive care unit. METHODS: All patients who underwent cardiothoracic surgery and were admitted to the cardiothoracic surgery intensive care unit between September 13, 2007, and November 1, 2007, were enrolled. Clinical and metabolic data were prospectively collected. All patients received intensive insulin therapy using a nurse-driven dynamic protocol targeting blood glucose values of 80 to 110 mg/dL. Four stages of critical illness were defined as follows: acute critical illness (intensive care unit days 0-2), prolonged acute critical illness (intensive care unit 3 or more days), chronic critical illness (tracheotomy performed), and recovery (liberated from ventilator). RESULTS: One hundred fourteen patients were enrolled. Seventy-three (64%) recovered during acute critical illness, 26 (23%) recovered during prolonged acute critical illness, and 15 (13%) progressed to chronic critical illness. All 6 deaths were among patients in chronic critical illness. Admission blood glucose and average blood glucose values for the first 12 hours were lower in patients who developed chronic critical illness and died and were higher in patients who developed chronic critical illness and survived (P = .007 and P = .007, respectively). Severe hypoglycemia (blood glucose <40 mg/dL) occurred once (0.03% of all measurements). Lower initial blood glucose values, which reflect an impaired stress response immediately after surgery, were associated with increased mortality, and a significant delay in achieving tight glycemic control with intensive insulin therapy was associated with prolonged intensive care unit course, but no increase in mortality. CONCLUSION: The study findings suggest that acute postoperative hyperglycemia and its prompt correction with intensive insulin therapy are associated with favorable outcomes in patients in the cardiothoracic surgery intensive care unit. PMID- 20350913 TI - A prospective trial of U500 insulin delivered by Omnipod in patients with type 2 diabetes mellitus and severe insulin resistance. AB - OBJECTIVE: To test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance. METHODS: In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod. RESULTS: Twenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P<.001) and significantly increased the percentage of time spent in the blood glucose target range (70-180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P<.001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion. CONCLUSIONS: U500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin resistant type 2 diabetic population. PMID- 20350910 TI - New treatment modalities in osteoporosis. AB - OBJECTIVE: To describe recently discovered agents for the management of osteoporosis. METHODS: A literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included. RESULTS: In menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor kappaB; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/beta-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven. CONCLUSIONS: New developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile. PMID- 20350914 TI - Survey on transition from inpatient to outpatient for patients on insulin: what really goes on at home? AB - OBJECTIVE: To identify the diabetes-specific, posthospital discharge issues that may arise for patients sent home on insulin therapy. METHODS: We designed and conducted a telephone survey covering predischarge issues such as survival skill education and insulin discharge instructions, postdischarge logistical problems such as obtaining diabetes medications and supplies, and overall glucose control. The questionnaire was administered by telephone 1 week after discharge from the hospital to adult patients sent home on long-acting insulin. RESULTS: We attempted to contact 61 patients who were eligible for the study. Eleven patients were unable to be reached by telephone despite multiple attempts. Forty-seven of 50 patients contacted agreed to be interviewed. Nearly 100% of patients received appropriate "survival skills" training, including instruction regarding self monitoring of blood glucose, insulin administration, and treatment of hypoglycemia. Once discharged, 10 patients (21%) had difficulty obtaining diabetes medications and supplies. Thirty-seven patients (79%) felt that their blood glucose control was "good" in the week after they left the hospital compared with author perception of 25 patients having good glucose control (53%) on the basis of pre-defined criteria. Although patients received instruction on insulin dosing and when and who to call for problems and questions, specific guidelines on how to manage insulin in the setting of changing glucocorticoid dosages were not communicated to patients. CONCLUSIONS: On the basis of our findings, we anticipate implementing improvements in diabetes-specific discharge prescriptions, new guidelines on when patients should call for assistance, and specific orders on how to adjust insulin for changes in glucocorticoid dosages. PMID- 20350915 TI - Treatment of thyroid-associated orbitopathy with rituximab--a novel therapy for an old disease: case report and literature review. AB - OBJECTIVE: To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder the stiff person syndrome (SPS). METHODS: We present a case report and a review of the related literature. RESULTS: A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye>right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye>right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change. CONCLUSION: Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody. PMID- 20350916 TI - Male sex, African American race or ethnicity, and triiodothyronine levels at diagnosis predict weight gain after antithyroid medication and radioiodine therapy for hyperthyroidism. AB - OBJECTIVE: To determine whether racial or ethnic differences affect weight gain after treatment of hyperthyroidism and to reassess established risk factors such as sex, age, and cause of hyperthyroidism. METHODS: We conducted a retrospective review of medical records of 111 patients treated with radioiodine (RAI) for hyperthyroidism, with or without preceding antithyroid medication, during 2002 to 2005. We ascertained age, sex, race or ethnicity, insurance status, compliance with visits, serum triiodothyronine (T3) level at diagnosis, and cause of hyperthyroidism. Weights and serum thyroidstimulating hormone levels were obtained at diagnosis, at time of RAI therapy, and at 0 to 4 months, 4 to 8 months, 8 to 12 months, and 24 months after RAI treatment. RESULTS: There was a significant weight increase after treatment of hyperthyroidism. Levels of T3 at initial diagnosis of hyperthyroidism, male sex, and black or Hispanic ethnicity were found to be independent predictors of weight gain after RAI treatment. We found a significant interaction between race or ethnicity and sex in multivariate models. There was no difference in thyroid function across racial or ethnic groups or the sexes. Age, cause of hyperthyroidism, posttreatment thyroid stimulating hormone level, compliance, and insurance status were not found to be significant predictors of weight gain. CONCLUSION: The T3 level at the time of diagnosis of hyperthyroidism is a strong predictor of weight gain after treatment of hyperthyroidism. Black race or ethnicity and male sex are also risk factors for weight gain. PMID- 20350917 TI - Effect of dexamethasone on oral glucose tolerance in healthy adults. AB - OBJECTIVE: To determine the dose-response and time course of action of a single dose of dexamethasone on plasma glucose and insulin dynamics in healthy adults. METHODS: Participants included healthy adults who met the following inclusion criteria: 18 to 65 years of age, body mass index of 18 to 25 kg/m2, no family history of diabetes mellitus, not taking any medication known to affect glucose tolerance, and nonpregnant state for female participants. Each participant underwent 3 sequential blocks of 75-g oral glucose tolerance tests (OGTTs) on days 1, 2, and 3; this sequence was repeated on 3 different occasions separated by more than 2 weeks. On the first day of each block, participants reported to the research center after a 10- to 12-hour overnight fast, and fasting baseline blood samples for glucose, insulin, and C-peptide were obtained. Baseline (0 mg) OGTT was then performed with a 75-g glucose load, and blood samples were collected at 30, 60, 90, and 120 minutes for measurements of glucose, insulin, and C-peptide. After the baseline OGTT on day 1, a single dose of either 2-, 4- or 8-mg of dexamethasone was administered orally. Twenty-four and 48 hours later, participants returned for additional OGTTs. RESULTS: Ten healthy volunteers (4 male and 6 female) were enrolled. The effect of dexamethasone was maximal 24 hours after 8-mg dexamethasone compared with the effect observed after no dexamethasone administration. At 60 minutes during the OGTT (following 8-mg dexamethasone), blood glucose increased from 127 +/- 7.1 mg/dL (6.35 +/- 0.36 mmol/L) to 176 +/- 19 mg/dL (8.8 +/- 0.95 mmol/L), insulin increased from 49.3 +/ 3.2 MUIU/mL (342 +/- 22 pmol/L) to 119.7 +/- 10.1 MUIU/mL (831 +/- 70 pmol/L), and C-peptide increased from 6376 +/- 510 pg/L (1913 +/- 153 pmol/L) to 10 143 +/ 1016 pg/L (3043 +/- 305 pmol/L); the 60-minute levels returned towards baseline at 48 hours. Smaller changes were observed with 2- and 4-mg dexamethasone. Twenty four hours after 8-mg dexamethasone, there was a 2.2- and 1.5-fold increase in homeostasis model assessment of insulin resistance and homeostasis model assessment of beta cells, respectively, and a 2.5-fold decrease in the Matsuda sensitivity index. CONCLUSIONS: A single oral dose of 8-mg dexamethasone increases blood glucose, insulin, and C-peptide levels maximally at 24 hours, 1 hour following 75-g OGTT. A dexamethasone stress test might identify persons at increased risk for type 2 diabetes. PMID- 20350918 TI - Effect of dexamethasone on insulin secretion: examination of underlying mechanisms. AB - OBJECTIVE: To study the mechanism of increased insulin secretion in response to short-term administration of dexamethasone. METHODS: Male Wistar rats were injected intraperitoneally with dexamethasone (dexamethasone; 200 mcg/kg body weight per day) or saline for 3 consecutive days. Insulin secretion in response to glucose, ionomycin, and KCl was quantified in islets isolated from the animals, and the amount of glucokinase was measured by Western blot. RESULTS: Dexamethasone-treated animals had 1.18-fold higher fasting blood glucose concentration and 6.5-fold increase in fasting serum insulin concentration compared with findings from animals injected with saline. Compared with islets isolated from control rats, islets from dexamethasone-treated rats secreted more insulin at 60 minutes in response to 5.5 mM glucose (416.4 vs 115.6 fmoles/10 islets, P = .011) and in response to 16.6 mM glucose (985.5 vs 520.6 fmoles/10 islets, P = .014); no change in insulin secretion was observed at 10 minutes. Insulin secretion from islets of dexamethasone-treated rats and control rats was not differentially augmented in response to either ionomycin or potassium chloride. Glucokinase expression was not altered by treatment with dexamethasone. CONCLUSIONS: Augmentation of insulin secretion in response to glucose in the pancreatic islets from dexamethasone-treated rats is preserved in islets studied in vitro. The increase in glucose-stimulated insulin secretion appears to be mediated by steps upstream to beta-cell membrane depolarization and the attended increase in intracellular calcium in the signaling pathway of insulin secretion. PMID- 20350919 TI - Parathyroidectomy-induced thyroiditis. AB - OBJECTIVE: To highlight the possibility of development of thyroiditis after parathyroidectomy. METHODS: Clinical and laboratory findings in 2 cases are presented, and the relevant literature is reviewed. RESULTS: In 2 women (84 years old and 55 years old) with no history of thyroid disease in one of them and a remote history of excision of a follicular adenoma in the other, thyrotoxicosis developed a few days to a week after parathyroidectomy for primary hyperparathyroidism. The first patient underwent bilateral cervical exploration with removal of a right inferior parathyroid adenoma, whereas the second patient had excision of 3 1/2 parathyroid glands for 4-gland hyperplasia and 2 benign nodules from the left thyroid lobe. Both surgical procedures were uncomplicated. Neither patient had received any iodinated contrast agents or medications such as lithium or amiodarone before presentation. Laboratory results showed elevated levels of free thyroxine, suppressed thyroid-stimulating hormone levels, very low radioiodine uptake (in the second patient), and an elevated thyroglobulin level (in the first patient). Both patients were treated symptomatically with beta adrenergic antagonists. Thyroid function normalized and symptoms diminished after 1 to 2 months. CONCLUSION: Parathyroidectomy-induced thyroiditis is underrecognized. The majority of patients are asymptomatic, although clinically significant thyrotoxicosis can also occur. Candidates for parathyroidectomy should be informed of this potential complication, and thyroid function should be assessed if clinically indicated. PMID- 20350920 TI - Improved in vitro fertilization outcomes after treatment of subclinical hypothyroidism in infertile women. AB - OBJECTIVE: To assess the effect of treatment of maternal subclinical hypothyroidism on infertility outcome. METHODS: Between April 1, 2006, and April 22, 2007, we conducted a prospective, randomized trial in infertile women with subclinical hypothyroidism who elected to undergo in vitro at the Shatby University Hospital for Women in Alexandria, Egypt. Patients were randomly assigned to 2 groups: treatment group (group A) and placebo group (group B). Male factor infertility was ruled out. One month before the assisted reproduction technology procedure, group A underwent levothyroxine treatment with a dosage of 50 to 100 mcg daily, while group B started placebo. All patients underwent controlled ovarian stimulation. Patients who achieved pregnancy were followed up throughout their pregnancy until delivery. Levothyroxine treatment and placebo were maintained throughout pregnancy in group A and group B, respectively. RESULTS: Mean thyrotropin value was significantly lower in group A than in group B (1.1 +/- 0.3 mIU/L vs 4.9 +/- 0.7 mIU/mL, respectively). Mean number of retrieved oocytes was similar in both groups (6.19 +/- 0.74 [group A] vs 6.08 +/- 0.79 [group B]). Miscarriage rate was significantly lower in group A than in group B (9% vs 13%, respectively), and the clinical pregnancy rate and delivery rate were significantly higher in group A than in group B (35% and 10% vs 26% and 3%, respectively), indicating that the quality, not the quantity, of retrieved oocytes was more important. CONCLUSION: These preliminary data suggest that levothyroxine supplementation should be recommended to achieve clinical pregnancies in women with subclinical hypothyroidism who are undergoing in vitro fertilization-intracytoplasmic sperm injection. PMID- 20350921 TI - State-of-the-art inpatient diabetes care: the evolution of an academic hospital. PMID- 20350922 TI - Comparison of type 2 diabetes care in the United States and Japan. PMID- 20350923 TI - Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. AB - OBJECTIVE: To study the effect of improvement in vitamin D status on glucose tolerance in Asian Indian patients with moderately controlled type 2 diabetes mellitus (T2DM). METHODS: This randomized, double-blind, placebo-controlled pilot study was conducted in 28 Asian Indian patients with T2DM. Study participants were randomly assigned to a vitamin D-treated group (group D) or a placebo group (group P). Serum 25-hydroxyvitamin D, hemoglobin A1c, and serum fructosamine levels were measured, and an oral glucose tolerance test (OGTT) was performed in all patients at baseline and 4 weeks after intervention. During the OGTT, plasma glucose and serum insulin levels were measured at 0, 30, 60, 90, and 120 minutes. The unpaired t test was used to compare the groups at baseline and to compare the differences in changes from baseline to 4 weeks between the 2 study groups. RESULTS: Group D and group P were similar with respect to their fasting plasma glucose and serum insulin concentrations, post-OGTT plasma glucose and serum insulin levels, and hemoglobin A1c and fructosamine values at baseline. Serum 25 hydroxyvitamin D levels increased significantly in group D at 4 weeks. No significant differences were found between the groups at baseline and 4 weeks with respect to serum fructosamine, fasting plasma glucose and serum insulin, post-OGTT plasma glucose and serum insulin levels, and homeostasis model assessment of insulin resistance. CONCLUSION: In this study, short-term improvement in vitamin D status was not associated with improvement in glucose tolerance, insulin secretion, or insulin sensitivity in Asian Indian patients with moderately controlled T2DM. PMID- 20350924 TI - Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus. AB - OBJECTIVE: To compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes. METHODS: This 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite > or =3 months of sulfonylurea or metformin monotherapy, to receive add on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels < or =7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia. RESULTS: At end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/dL; 95% confidence interval, -47.6 to -22.2; P<.0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatment-emergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose <70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P<.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups. CONCLUSION: The addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in <5% of patients in the insulin glargine treatment group. PMID- 20350925 TI - Papillary carcinoma of the thyroid with fibromatosislike stroma: case report and review of literature. AB - OBJECTIVE: To describe a case of papillary carcinoma of the thyroid with fibromatosislike stroma, emphasize the need for a diligent search for papillary thyroid cancer in the presence of a fibroproliferative lesion, highlight the peculiar hormonal response of the stromal component, and review the pertinent literature. METHODS: We present the clinical, laboratory, radiologic, and pathologic findings in a patient with papillary carcinoma of the thyroid with fibromatosislike stroma and review the related published material. RESULTS: A 29 year-old woman presented to our surgical department because of a large mediastinal mass. She underwent surgical removal of the mass by means of a median sternotomy and neck extension. Pathology examination revealed macroscopically tan scarlike tissue, which by histologic study consisted of a dominant fibroproliferative lesion overshadowing a minor component of papillary carcinoma of the thyroid. Further neck exploration with total thyroidectomy revealed multifocal papillary carcinoma of the thyroid. Postoperatively, the patient received radioiodine treatment. A local and aggressive recurrent tumor was observed during a subsequent pregnancy; the lesion was not amenable to complete resection but fascinatingly responded to antiestrogen therapy (orally administered tamoxifen). CONCLUSION: The presence of a fibroproliferative lesion could be misleading. A diligent search should be made for a papillary thyroid carcinoma component within fibromatosislike stroma. The mode of manifestation of the tumor and its response to hormonal manipulation are distinctive features of this case. PMID- 20350926 TI - Utilization patterns and user characteristics of an ad libitum Internet weight loss program. AB - BACKGROUND: The Internet holds promise for the delivery of evidence-based weight loss treatment to underserved populations. However, most studies do not reflect the more naturalistic and common ad libitum, or freely at will, use of the Internet. Randomized clinical trials, for example, typically include at least some direct contact with participants and often have restrictive selection criteria. There is a paucity of research examining utilization patterns of online weight loss programs, particularly in the rapidly expanding direct-to-consumer arena. OBJECTIVES: To examine self-reported characteristics (age, body mass index [BMI], gender), behaviors, and Internet site utilization patterns of a sample of users of a direct-to-consumer ad libitum Internet weight loss program. METHODS: This study is based on analysis of archival data from the initial 15 weeks of an ongoing, free, evidence-based, direct-to-consumer Internet weight loss program, the Healthy Weight Center, which included standard information about nutrition, fitness, and behavioral strategies; monitoring tools; and moderated support group message boards. Participants encountered the program through self-directed Internet searches and anonymously registered to utilize the site. Self-reported user characteristics and electronically tracked utilization data were extracted from existing program data, compiled, and examined. Pearson correlations were computed to examine the association of program utilization with age and BMI. One way analysis of variance (ANOVA) was used for gender comparisons. RESULTS: We examined data from the first 204 adult users of the program who were classified as either overweight (BMI 25 to < 30 kg/m(2)) or obese (BMI > or = 30 kg/m(2)). The mean age of participants was 42.0 years (SD 11.7), 81.9% (167/204) were women, and mean BMI was 32.01 kg/m(2) (SD 6.26). The percent of participants who used program tools was as follows: 13.7%, meal planner; 10.8%, nutrition lookup: 17.6%, activity log; 14.2%, journal; and 22.1%, weight tracker. Participants also used the following educational resources: nutrition, 13.2%; fitness, 6.4%; and behavioral, 7.4%. Of the personal self-assessments available through the program, 57.8% of participants assessed personal barriers, and 50.5% assessed relationship with food. Only 7.8% used the support group message boards. No significant associations between site utilization and age, gender, or BMI were found. Reasons for wanting to lose weight were: health, 87%; appearance, 74%; mobility, 44%; doctor recommendation, 23%; and spouse/friend suggested, 12%. The age participants reported first becoming overweight was young adulthood, 31%; late adulthood, 28%; childhood, 22%; adolescence, 17%; and as a toddler, 3%. Self perceived factors contributing to weight gain were lack of exercise for 70% of participants, emotions for 62%, overeating for 61%, and slow metabolism for 33%. CONCLUSIONS: Internet weight loss programs reach many people who cannot access traditional treatment. However, users appear not to be optimally utilizing key aspects of the weight loss intervention, such as education, monitoring, and support. This study provides insight into the patterns of ad libitum use of an online weight loss program across multiple treatment-related domains in a naturalistic Internet environment. PMID- 20350927 TI - Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. AB - BACKGROUND: Plasma cystatin C (pCysC) has been proposed as an alternative to plasma creatinine (pCr) as a measure of renal function. We compared the detection of functional change by both biomarkers in critically ill patients. METHODS: pCysC and pCr were measured on admission to one of two intensive care units (ICU) and then daily over 7 days. Patients were classified according to the analyte that first increased by either >=25 or >=50% above the admission value. The proportion of patients in each class was compared using McNemar's chi-square test. Sustained acute kidney injury (AKI, a >=50% increase in pCr from baseline for >=24 h), dialysis and death within 30 days were recorded. The ability of pCysC and pCr on admission to predict sustained AKI, dialysis or death was assessed from the area under the receiver operator characteristic curve (AUC). RESULTS: Of 442 patients, 83 had a >=50% increase in one analyte, 17 in both and 342 in neither. Comparable numbers for a >=25% increase were 163 in one analyte, 45 in both and 234 in neither. pCysC increased prior to pCr more frequently than vice versa in both the cohort with a >=50% increase (P < 0.0001) and with a >=25% increase (P < 0.0001). pCysC predicted sustained AKI with an AUC of 0.80 [95% confidence interval (CI) = 0.71-0.88]. pCysC and pCr were similarly moderately predictive of death or dialysis with AUCs of 0.61 [95% CI = 0.53-0.68] and 0.60 [95% CI = 0.51-0.67], respectively. CONCLUSION: pCysC was an effective and earlier surrogate marker of decreased renal function than pCr in a general ICU population. PMID- 20350928 TI - Managing hypertension using home blood pressure monitoring among haemodialysis patients--a call to action. PMID- 20350929 TI - An inducible RNA interference system for the functional dissection of mouse embryogenesis. AB - Functional analysis of multiple genes is key to understanding gene regulatory networks controlling embryonic development. We have developed an integrated vector system for inducible gene silencing by shRNAmir-mediated RNA interference in mouse embryos, as a fast method for dissecting mammalian gene function. For validation of the vector system, we generated mutant phenotypes for Brachyury, Foxa2 and Noto, transcription factors which play pivotal roles in embryonic development. Using a series of Brachyury shRNAmir vectors of various strengths we generated hypomorphic and loss of function phenotypes allowing the identification of Brachyury target genes involved in trunk development. We also demonstrate temporal control of gene silencing, thus bypassing early embryonic lethality. Importantly, off-target effects of shRNAmir expression were not detectable. Taken together, the system allows the dissection of gene function at unprecedented detail and speed, and provides tight control of the genetic background minimizing intrinsic variation. PMID- 20350930 TI - Visualizing helicases unwinding DNA at the single molecule level. AB - DNA helicases are motor proteins that catalyze the unwinding of double-stranded DNA into single-stranded DNA using the free energy from ATP hydrolysis. Single molecule approaches enable us to address detailed mechanistic questions about how such enzymes move processively along DNA. Here, an optical method has been developed to follow the unwinding of multiple DNA molecules simultaneously in real time. This was achieved by measuring the accumulation of fluorescent single stranded DNA-binding protein on the single-stranded DNA product of the helicase, using total internal reflection fluorescence microscopy. By immobilizing either the DNA or helicase, localized increase in fluorescence provides information about the rate of unwinding and the processivity of individual enzymes. In addition, it reveals details of the unwinding process, such as pauses and bursts of activity. The generic and versatile nature of the assay makes it applicable to a variety of DNA helicases and DNA templates. The method is an important addition to the single-molecule toolbox available for studying DNA processing enzymes. PMID- 20350932 TI - Alcohol policy in a Russian region: a stakeholder analysis. AB - BACKGROUND: Male life expectancy in the Russian Federation, at 60 years, is the lowest in Europe. Several factors contribute to this situation, but hazardous consumption of alcohol is especially a key factor. METHODS: We undertook a stakeholder analysis in a typical Russian region located on the western side of the Urals. Organizations with a stake in alcohol policy in the region were identified by snowball sampling and information on their position and influence on alcohol policy was elicited from interviews with key informants. Their interests and influence were mapped and their relationships plotted. RESULTS: Twenty-nine stakeholder organizations were identified and 43 interviews were conducted with their staff. The most influential actors were the Federal and regional governments, large beer producers and manufacturers of strong alcohols. However, the majority of organizations that might be expected to play a role in developing or implementing alcohol control policies were almost entirely disengaged and fragmented. No evidence was found of an existing or emerging multi sectoral coalition for developing alcohol policy to improve health. Organizations that might be expected to contribute to tackling hazardous drinking had little understanding of what might be effective. CONCLUSIONS: While stakeholders with an interest in maintaining or increasing alcohol consumption are engaged and influential, those who might seek to reduce it either take a very narrow perspective or are disengaged from the policy agenda. There is a need to mobilize actors who might contribute to effective policies while challenging those who can block them. PMID- 20350931 TI - Mechanism of sequence-specific template binding by the DNA primase of bacteriophage T7. AB - DNA primases catalyze the synthesis of the oligoribonucleotides required for the initiation of lagging strand DNA synthesis. Biochemical studies have elucidated the mechanism for the sequence-specific synthesis of primers. However, the physical interactions of the primase with the DNA template to explain the basis of specificity have not been demonstrated. Using a combination of surface plasmon resonance and biochemical assays, we show that T7 DNA primase has only a slightly higher affinity for DNA containing the primase recognition sequence (5'-TGGTC-3') than for DNA lacking the recognition site. However, this binding is drastically enhanced by the presence of the cognate Nucleoside triphosphates (NTPs), Adenosine triphosphate (ATP) and Cytosine triphosphate (CTP) that are incorporated into the primer, pppACCA. Formation of the dimer, pppAC, the initial step of sequence-specific primer synthesis, is not sufficient for the stable binding. Preformed primers exhibit significantly less selective binding than that observed with ATP and CTP. Alterations in subdomains of the primase result in loss of selective DNA binding. We present a model in which conformational changes induced during primer synthesis facilitate contact between the zinc-binding domain and the polymerase domain. PMID- 20350933 TI - Unfair? It depends: neural correlates of fairness in social context. AB - Fairness is a key concept in social interactions and is influenced by intentionality considerations. In this functional magnetic resonance imaging study, we investigated the neural correlates of fairness by focusing on responder behavior to unfair offers in an Ultimatum Game paradigm with conditions that differed in their intentionality constraints. Brain activity underlying rejection vs acceptance of unfair offers appeared highly dependent on intentionality. Rejection of unfair offers when the proposer had no-alternative as well as acceptance of offers when the proposer had a fair- or hyperfair-alternative was associated with activation in a network of regions including the insula and the dorsal medial prefrontal cortex. These activations were interpreted as neural responses to norm violations because they were mostly involved when behavior was inconsistent with socially accepted behavior patterns. Rejection of unfair offers in the no-alternative condition further resulted in activity in the anterior medial prefrontal cortex and the temporoparietal junction, which was interpreted in terms of higher moral mentalizing demands required in social decision-making when rejection could not be readily justified. Together, results highlight the significance of intentionality considerations in fairness-related social decision making processes. PMID- 20350934 TI - Utilization of inpatient care from private hospitals: trends emerging from Kerala, India. AB - BACKGROUND: There is a gap in knowledge on the overall role and characteristics of private health care providers in India. This research is aimed at understanding changes in the consumption of inpatient care services from private hospitals between 1986 and 2004, with a particular focus on equitable outreach. METHODS: Secondary analysis of National Sample Survey data on the utilization of inpatient care services in Kerala is performed for the periods 1986-87, 1995-96 and 2004. Household survey data are examined to understand the users of the private health system as there are limitations in obtaining reliable data from unregulated private health care providers. FINDING: The annual hospitalization rate increased from 69 per 1000 population in 1986-87 to 126 per 1000 population by 2004. The proportion of persons seeking care from private rather than government hospitals increased from 55% in 1986-87 to 65% by 2004. Concentration indices revealed that the year 1995-96 witnessed the highest income inequality in hospitalization rates. A decline both in hospitalization rates and in the relative preference for private hospitals over government hospitals among the poorest two quintiles between 1986-87 and 1995-96 indicates that the poor avoided inpatient treatment. The rich-poor divide in care seeking from private hospitals was moderated by 2004. CONCLUSION: Improvements in the purchasing power of the population, and the strategy of private hospitals in this highly competitive market to generate revenue from the poorer quintiles by offering different pricing options, have reduced the observed rich-poor divide in the consumption of inpatient treatment from this sector. However, while this gap in utilization has closed, the burden of out-of-pocket expenditure is higher among the poor. PMID- 20350935 TI - How psychogenic is dystonia? Views from past to present. AB - In the last few centuries, there has been a constant sway between organic and psychogenic explanations for dystonia. In the current study, we investigate this history, assuming the perspective of a spectrum from organic to psychogenic, between which ideas were moving. We have focussed on (i) primary generalized dystonia, (ii) cervical dystonia, (iii) writer's cramp and (iv) fixed dystonia related to complex regional pain syndrome. We have studied medical texts published since the 19th century and their references. Jean-Martin Charcot advocated the concept of hysteria, disorders in which, besides predisposition, environmental factors were involved in their pathogenesis. Sigmund Freud introduced psychoanalysis as an explanatory therapy for psychic disorders. Previous theories, together with the lack of an organic substrate for dystonia, made a strong case for psychogenic explanations. Consequently, many dystonia patients were told that they suffered from psychological conflicts and were treated for them. However, after the description of new hereditary cases in the 1950s, the limited efficacy of psychotherapy in torsion dystonia, the effects of surgical treatments and the lesion studies in the 1960s, more physicians became convinced of the organic nature. The culminating point was the discovery of the DYT1 gene in 1997. In the meantime, experts had already convinced the neurological community that cervical dystonia and writer's cramp were focal dystonias, i.e. minor forms of generalized dystonia, and therefore organic disorders. In contrast, the pathophysiology of fixed dystonia related to complex regional pain syndrome remained controversial. Knowledge of this history, which played on the border between neurology and psychiatry, is instructive and reflects the difficulty in discriminating between them. Today, new insights from functional imaging and neurophysiological studies again challenge the interpretation of these disorders, while the border between psychogenic and organic has become more blurred. Abnormalities of sensorimotor integration and cortical excitability that are currently supposed to be the underlying cause of dystonia bring us back to Sherringtonian physiology. We suggest that this may lead to a common explanation of the four afflictions of which we have traced the history. PMID- 20350936 TI - Evidence for gamma inhibition deficits in the dorsolateral prefrontal cortex of patients with schizophrenia. AB - Previous studies have shown that patients with schizophrenia and bipolar disorder have deficits in cortical inhibition. Through the combination of interleaved transcranial magnetic stimulation and electroencephalography, we have recently reported on methods in which cortical inhibition can be measured from the dorsolateral prefrontal cortex, a cortical region that is more closely associated with the pathophysiology of schizophrenia. Furthermore, it is possible to index cortical inhibition of specific oscillatory frequencies including the gamma band (30-50 Hz) whose modulation has been related to higher order cortical processing. In this study, we show that patients with schizophrenia have significant deficits of cortical inhibition of gamma oscillations in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder, while no deficits are demonstrated in the motor cortex. These results suggest that the lack of inhibition of gamma oscillations in the dorsolateral prefrontal cortex may represent an important frontal neurophysiological deficit, which may be responsible for the spectrum of deficits commonly found in schizophrenia. PMID- 20350937 TI - The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. AB - Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology specific genetic determinants in radiation-related PTC. PMID- 20350938 TI - What was the immediate impact on population health of the recent fall in hormone replacement therapy prescribing in England? Ecological study. AB - BACKGROUND: The publication in 2002 of the women's health initiative (WHI) trial revealed long-term risks and benefits of hormone replacement therapy (HRT). Increased cardiovascular disease, venous thromboembolism and breast cancer risks outweighed benefits on hip fracture, colorectal and endometrial cancer. We investigated whether the subsequent 50% fall in HRT use in England impacted on population rates of these outcomes. METHODS: Time-series analysis of hospital admissions, incidence and mortality amongst women aged 50-69, England 1997-2006. RESULTS: There was no relationship between reduced HRT prescribing after 2002 and trends in breast cancer, colorectal cancer or hip fracture. Amongst 50-59 year olds, the annual percentage change in venous thromboembolism hospitalizations fell from 0.0% [95% confidence interval (CI): -2.3 to 2.3%] between 1997 and 2000 to -5.7% (-7.7 to -3.6%) between 2000 and 2006 (P-value = 0.001); the annual change in endometrial cancer mortality increased from 0.7% (-3.2 to 4.8%) between 1997 and 2003 to 11.0% (0.2 to 22.9%) after 2003 (P-value = 0.07); and previously falling acute myocardial infarction hospitalizations (annual change: -6.8%) and stroke (-3.0%) stabilized (-0.4%) or increased (+0.8%), respectively, around 2001 (P < 0.0001). CONCLUSION: Although rates of venous thromboembolism (decline) and endometrial cancer mortality (increase) changed in line with WHI findings, the decline in venous thromboembolism may have started before 2002 and increased fatal endometrial cancers could be a chance finding. PMID- 20350939 TI - The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency. AB - CONTEXT: The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. OBJECTIVE: The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. DESIGN AND SETTING: This was a prospective study conducted in two Pediatric Endocrinology Centers. PATIENTS AND METHODS: Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. RESULTS: The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. CONCLUSIONS: This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency. PMID- 20350940 TI - LIN28B in constitutional delay of growth and puberty. AB - BACKGROUND: Recently variation in LIN28B, a human ortholog of the gene-regulating processing of micro-RNAs (miRNAs) controlling the timing of major developmental events in the nematode Caenorhabditis elegans, was reported to be associated with timing of puberty in humans. In C. elegans, a gain-of-function allele of lin-28 causes a retarded phenotype. OBJECTIVE: The objective of the study was to evaluate the variation in the LIN28B gene in 145 subjects with constitutional delay of growth and puberty (CDGP). PATIENTS AND METHODS: For this study, 115 males and 30 females with CDGP were included. CDGP was defined by Tanner genital or breast stage II and pubertal growth spurt taking place 2 SD later than average. The four coding exons (exons 1-4) and exon-intron boundaries, as well as the fragment of 3' untranslated region containing miRNA recognition elements A and B, of LIN28B were PCR amplified from genomic DNA obtained from peripheral blood leukocytes of the subjects and bidirectionally sequenced. RESULTS: No variation in the coding region of LIN28B in the 145 subjects with CDGP was found. However, 16 of 145 subjects carried a 2-nucleotide deletion immediately 5' from miRNA recognition element A. These patients did not differ in phenotypic features as compared with noncarriers, and this variant was present in 100 controls with the same frequency. CONCLUSIONS: Our results show that mutations in the coding region or 3' untranslated region miRNA recognition elements A and B of LIN28B do not underlie CDGP. Lack of any variation in the coding region of the gene suggests that LIN28B in developmental timing is so crucial that any changes in the conserved protein would probably be lethal. PMID- 20350941 TI - Evaluation of Etest to determine tigecycline MICs for Enterobacter species. PMID- 20350942 TI - Effect of vicriviroc on the QT/corrected QT interval and central nervous system in healthy subjects. AB - Vicriviroc is a CCR5 antagonist in clinical development for the treatment of HIV 1. Two phase I studies were conducted to assess the safety of vicriviroc. One study characterized the drug's potential to prolong the QT/corrected QT (QTc) interval and to induce arrhythmia. In this partially blind, parallel-group study, 200 healthy subjects aged 18 to 50 years were randomized in equal groups to the following regimens: (i) placebo for 9 days and a single dose of moxifloxacin at 400 mg on day 10, (ii) placebo, (iii) vicriviroc-ritonavir (30 and 100 mg), (iv) vicriviroc-ritonavir (150 and 100 mg), and (v) ritonavir (100 mg). The second study characterized the effects of a range of vicriviroc doses on the central nervous system (CNS). In this third-party-blind, parallel-group study, 30 healthy subjects aged 18 to 48 years were randomized to receive a single dose of either vicriviroc at 200, 250, or 300 mg or placebo, followed by multiple (seven) once daily doses of either vicriviroc at 150, 200, or 250 mg or placebo, respectively. In the first study, vicriviroc produced no clinically meaningful effect on the QT/QTc interval when administered at a supratherapeutic or therapeutic dose concurrently with ritonavir. In the second study, vicriviroc produced no observable seizure activity, nor was it held to be associated with any clinically relevant changes in brain waveforms in the final consensus of reviewers. These findings showed that vicriviroc produced no clinically relevant QTc prolongation cardiac or epileptogenic effects in healthy individuals at exposures as high as five times those expected for HIV-infected patients receiving therapeutic doses of vicriviroc in a ritonavir-boosted protease inhibitor-containing regimen. PMID- 20350943 TI - Emergence of ciprofloxacin-nonsusceptible Streptococcus pyogenes isolates from healthy children and pediatric patients in Portugal. AB - We describe 66 ciprofloxacin-nonsusceptible Streptococcus pyogenes isolates recovered from colonized and infected children. The ParC S79A substitution was frequent and associated with the emm6/sequence type 382 (emm6/ST382) lineage. The ParC D83G substitution was detected in two isolates (emm5/ST99 and emm28/ST52 lineages). One isolate (emm89/ST101) had no quinolone resistance-determining region codon substitutions or other resistance mechanisms. Five of 66 isolates were levofloxacin resistant. Although fluoroquinolones are not used in children, they may be putative disseminators of fluoroquinolone-nonsusceptible strains in the community. PMID- 20350944 TI - Madurella mycetomatis is not susceptible to the echinocandin class of antifungal agents. AB - Eumycetoma caused by Madurella mycetomatis is treated surgically and with high doses of ketoconazole. Therapeutic responses are poor, and recurrent infections are common. In search of therapeutic alternatives in the treatment of mycetoma, we determined the in vitro susceptibilities of M. mycetomatis isolates against caspofungin, anidulafungin, and micafungin. As a comparator fungus, Aspergillus fumigatus was used. Minimal effective concentrations (MECs) and MICs were assessed and compared to those of ketoconazole. M. mycetomatis isolates were not susceptible to the echinocandins. PMID- 20350945 TI - Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus. AB - West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1 treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30 mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 microg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 microg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted. PMID- 20350946 TI - Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. AB - Artemisinin and its derivatives are the most rapidly acting and efficacious antimalarial drugs currently available. Although resistance to these drugs has not been documented, there is growing concern about the potential for resistance to develop. In this paper we report the selection of parasite resistance to artelinic acid (AL) and artemisinin (QHS) in vitro and the molecular changes that occurred during the selection. Exposure of three Plasmodium falciparum lines (W2, D6, and TM91C235) to AL resulted in decreases in parasite susceptibilities to AL and QHS, as well as to mefloquine, quinine, halofantrine, and lumefantrine. The changes in parasite susceptibility were accompanied by increases in the copy number, mRNA expression, and protein expression of the pfmdr1 gene in the resistant progenies of W2 and TM91C235 parasites but not in those of D6 parasites. No changes were detected in the coding sequences of the pfmdr1, pfcrt, pfatp6, pftctp, and pfubcth genes or in the expression levels of pfatp6 and pftctp. Our data demonstrate that P. falciparum lines have the capacity to develop resistance to artemisinin derivatives in vitro and that this resistance is achieved by multiple mechanisms, to include amplification and increased expression of pfmdr1, a mechanism that also confers resistance to mefloquine. This observation is of practical importance, because artemisinin drugs are often used in combination with mefloquine for the treatment of malaria. PMID- 20350947 TI - ramR mutations in clinical isolates of Klebsiella pneumoniae with reduced susceptibility to tigecycline. AB - Five Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline (MIC, 2 microg/ml) were analyzed. A gene homologous to ramR of Salmonella enterica was identified in Klebsiella pneumoniae. Sequencing of ramR in the nonsusceptible Klebsiella strains revealed deletions, insertions, and point mutations. Transformation of mutants with wild-type ramR genes, but not with mutant ramR genes, restored susceptibility to tigecycline and repressed overexpression of ramA and acrB. Thus, this study reveals a molecular mechanism for tigecycline resistance in Klebsiella pneumoniae. PMID- 20350948 TI - Activity of drug combinations against dormant Mycobacterium tuberculosis. AB - Aerobic (5-day-old cultures) and nonreplicating (dormant) Mycobacterium tuberculosis (5-, 12-, and 19-day-old cultures) bacteria were treated with rifampin (R), moxifloxacin (MX), metronidazole (MZ), amikacin (AK), or capreomycin (CP) for 7, 14, and 21 days. R-MX-MZ-AK and R-MX-MZ-CP killed both aerobic and dormant bacilli in 21 days, as shown by lack of regrowth in solid and liquid media. R-MX-MZ-AK and R-MX-MZ-CP also caused a strong decrease of nonreplicating bacilli in 7 days in a cell-based dormancy model. PMID- 20350949 TI - In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses. AB - Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 muM (0.5 microg/ml) (50% effective concentrations [EC(50)s] of 0.19 to 22.48 muM and 0.03 to 3.53 microg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 muM (0.5 microg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs. PMID- 20350950 TI - Molecular epidemiology, sequence types, and plasmid analyses of KPC-producing Klebsiella pneumoniae strains in Israel. AB - Sporadic isolates of carbapenem-resistant KPC-2-producing Klebsiella pneumoniae were isolated in Tel Aviv Medical Center during 2005 and 2006, parallel to the emergence of the KPC-3-producing K. pneumoniae sequence type 258 (ST 258). We aimed to study the molecular epidemiology of these isolates and to characterize their bla(KPC)-carrying plasmids and their origin. Ten isolates (8 KPC-2 and 2 KPC-3 producing) were studied. All isolates were extremely drug resistant. They possessed the bla(KPC) gene and varied in their additional beta-lactamase contents. The KPC-2-producing strains belonged to three different sequence types: ST 340 (n = 2), ST 277 (n = 2), and a novel sequence type, ST 376 (n = 4). Among KPC-3-producing strains, a single isolate (ST 327) different from ST 258 was identified, but both strains carried the same plasmid (pKpQIL). The KPC-2 encoding plasmids varied in size (45 to 95 kb) and differed among each of the STs. Two of the Klebsiella bla(KPC-2)-carrying plasmids were identical to plasmids from Escherichia coli, suggesting a common origin of these plasmids. These data indicate that KPC evolution in K. pneumoniae is related to rare events of interspecies spread of bla(KPC-2)-carrying plasmids from E. coli followed by limited clonal spread, whereas KPC-3 carriage in this species is related almost strictly to clonal expansion of ST 258 carrying pKpQIL. PMID- 20350952 TI - Demonstration of the analgesic efficacy and dose-response of acetylsalicylic acid with pseudoephedrine. AB - To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single-dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double-blind, randomized, placebo controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well-tolerated and effective analgesic in 500- and 1000-mg doses when combined with pseudoephedrine. PMID- 20350953 TI - Opioid modulation of oxytocin release. AB - Analgesia or anesthesia is frequently used for women in labor. A wide range of opioid analgesics with vastly different pharmacokinetics, potencies, and potential side effects can be considered by physicians and midwives for laboring patients requesting pain relief other than a labor epidural. The past 50 years have seen the use of the classic mu opioid agonist morphine and other opioids diminish markedly for several reasons, including availability of epidural anesthetics, side effects, formulary restrictions, and concern for neonatal respiratory depression. Morphine is now primarily used in obstetrics to provide rest and sedation as appropriate for the stressed prodromal stages of a labor without sufficient cervical dilatation. This review discusses the scientific basis for opioid modulation of oxytocin release from the posterior pituitary and the practical implications of this relationship to explain well-known clinical observations of the effect of morphine on prodromal labor. PMID- 20350951 TI - Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate. AB - Drug resistance against dihydrofolate reductase (DHFR) inhibitors-such as pyrimethamine (PM)-has now spread to almost all regions where malaria is endemic, rendering antifolate-based malaria treatments highly ineffective. We have previously shown that the di-amino quinazoline QN254 [5-chloro-N'6'-(2,5 dimethoxy-benzyl)-quinazoline-2,4,6-triamine] is active against the highly PM resistant Plasmodium falciparum V1S strain, suggesting that QN254 could be used to treat malaria in regions with a high prevalence of antifolate resistance. Here, we further demonstrate that QN254 is highly active against Plasmodium falciparum clinical isolates, displaying various levels of antifolate drug resistance, and we provide biochemical and structural evidence that QN254 binds and inhibits the function of both the wild-type and the quadruple-mutant (V1S) forms of the DHFR enzyme. In addition, we have assessed QN254 oral bioavailability, efficacy, and safety in vivo. The compound displays favorable pharmacokinetic properties after oral administration in rodents. The drug was remarkably efficacious against Plasmodium berghei and could fully cure infected mice with three daily oral doses of 30 mg/kg. In the course of these efficacy studies, we have uncovered some dose limiting toxicity at higher doses that was confirmed in rats. Thus, despite its relative in vitro selectivity toward the Plasmodium DHFR enzyme, QN254 does not show the adequate therapeutic index to justify its further development as a single agent. PMID- 20350954 TI - Effects of multiple doses of ambrisentan on the pharmacokinetics of a single dose of digoxin in healthy volunteers. PMID- 20350955 TI - Effect of CYP2B6 genotype on the pharmacokinetics of sibutramine and active metabolites in healthy subjects. AB - Sibutramine is a pharmacologic intervention for the treatment of obesity. The effect of CYP2B6 genotypes on the pharmacokinetics of sibutramine and its active metabolites (desmethylsibutramine [M1] and didesmethylsibutramine [M2]) was evaluated in 57 healthy subjects. Each subject received a single oral dose of 10 or 15 mg sibutramine, and blood samples were collected up to 72 hours after dosing. The relationship between the genotypes and the pharmacokinetics of sibutramine, M1, and M2 was examined. A statistically significant difference in the elimination half-life (t(1/2)) of sibutramine M1 was found among the 3 genotype groups (P = .0006), between the *1/*1 and *1/*6 groups (P = .0001), and between the *1/*4 and *1/*6 groups (P = .012). The mean value of M1 t(1/2) in *1/*6 (33.3 +/- 10.5 hours) was about 58% and 61% greater than that of the *1/*1 group (21.0 +/- 7.4 hours) and the *1/*4 group (20.7 +/- 9.8 hours), respectively. No significant differences in area under the concentration-time curve or maximum plasma drug concentration were observed between the groups. The CYP2B6*6 allele may be associated with a lower metabolic clearance of the M1 metabolite of sibutramine in human subjects. PMID- 20350956 TI - Surface shape analysis with an application to brain surface asymmetry in schizophrenia. AB - Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some small but significant differences are observed between the the patient and control groups. We then investigate a particular type of asymmetry called torque. Differences in asymmetry are observed between the control and patient groups, which add strength to other observations in the literature. Further investigations of the midline plane location in the 2 groups and the fitting of nonplanar curved midlines are also considered. PMID- 20350957 TI - Bayesian profile regression with an application to the National Survey of Children's Health. AB - Standard regression analyses are often plagued with problems encountered when one tries to make inference going beyond main effects using data sets that contain dozens of variables that are potentially correlated. This situation arises, for example, in epidemiology where surveys or study questionnaires consisting of a large number of questions yield a potentially unwieldy set of interrelated data from which teasing out the effect of multiple covariates is difficult. We propose a method that addresses these problems for categorical covariates by using, as its basic unit of inference, a profile formed from a sequence of covariate values. These covariate profiles are clustered into groups and associated via a regression model to a relevant outcome. The Bayesian clustering aspect of the proposed modeling framework has a number of advantages over traditional clustering approaches in that it allows the number of groups to vary, uncovers subgroups and examines their association with an outcome of interest, and fits the model as a unit, allowing an individual's outcome potentially to influence cluster membership. The method is demonstrated with an analysis of survey data obtained from the National Survey of Children's Health. The approach has been implemented using the standard Bayesian modeling software, WinBUGS, with code provided in the supplementary material available at Biostatistics online. Further, interpretation of partitions of the data is helped by a number of postprocessing tools that we have developed. PMID- 20350958 TI - Strains of Epstein-Barr virus infecting multiple sclerosis patients. AB - Both epidemiological and experimental studies have indicated that the ubiquitous herpesvirus Epstein-Barr virus (EBV) plays a role in the pathogenesis of multiple sclerosis (MS). Some features of MS epidemiology, such as the decline in risk among migrants from high to low MS prevalence areas, suggest the presence of variant EBV strains that increase MS risk. The objective of this study was to investigate whether genetic variability in EBV is associated with MS. Genes encoding for two EBV antigens (EBNA1 and BRRF2) were sequenced in EBV isolates from 40 MS patients and a similar number of control subjects. These viral antigens were chosen for analysis because they are known to stimulate atypical immune responses in MS. Extensive sequence polymorphism was observed within the EBNA1 and BRRF2 genes in isolates from both MS patients and controls. Interestingly, several single nucleotide polymorphisms within the EBNA1 gene, and one within the BRRF2 gene, were found to occur at marginally different frequencies in EBV strains infecting MS patients versus controls. Although this study does not find a simple causal relationship between EBV strains and the occurrence of MS, the existence of haplotypes that occur at different frequencies in MS patients versus controls may provide an area for future study of the role of EBV strain variation in multiple sclerosis. PMID- 20350959 TI - Outcome of psychiatric symptoms presenting at onset of multiple sclerosis: a retrospective study. AB - Psychiatric disturbances may occur at the onset of multiple sclerosis. However, information on their outcome is lacking. Our objective was to document the characteristics of psychiatric symptoms at presentation of multiple sclerosis and to define the long-term evolution of psychiatric disturbances in these patients. Based on a clinical record analysis of patients with defined multiple sclerosis diagnosis and coming under the care of a university multiple sclerosis centre within the period 1997-2007, patients with both psychiatric and neurological symptoms at presentation were identified. Clinical data at onset and at last follow-up were considered. Among 682 evaluated patients, psychiatric disturbances were associated with multiple sclerosis onset in 16 cases (2.3%). Most patients (56%) presented with a mood disorder with clinical characteristics of a major depressive-like episode, five (32%) had psychotic symptoms. Initial psychiatric disturbances improved later than neurological symptoms, or never fully recovered, regardless of the concomitant use of psychotropic medications. In most of the subjects psychiatric disturbances tended to remain over the follow-up period and at last visit, after a mean follow-up of 7.6 years (+/-2.3), 14 subjects (87%) had a supplementary diagnosis of psychiatric illness. Psychiatric symptoms at onset of multiple sclerosis may be indicators of possible maintenance of psychiatric morbidity in a sizeable proportion of patients. PMID- 20350960 TI - Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis. AB - Magnetization transfer ratio (MTR) is a sensitive parameter to quantify the integrity of myelinated white matter in patients with multiple sclerosis. Lesional MTR decreases in the acute phase due to demyelination, and subsequently shows recovery depending on the degree of remyelination in the absence of axonal loss. Recovery of average lesion MTR therefore might prove a viable outcome measure to assess the effect of remyelinating agents. Our objective was to determine the required sample size for phase II multicentre clinical trials using the recovery of average lesion MTR as primary outcome measure. With 7-monthly MRI scans, the MTR evolution of 349 new enhancing lesions before and after enhancement was assessed in 32 MS patients from 5 centres. Multilevel models were fitted to the data yielding estimates for the variance components, which were applied in power calculations. Sample sizes were determined for placebo controlled, multicentre trials using lesional MTR recovery post-enhancement as primary outcome measure. Average lesion MTR decreased slightly in the build-up to enhancement, decreased dramatically during enhancement and showed recovery in the period after cessation. The power calculations showed that for a power of 80%, approximately 136 patients per trial (mean number of 6 lesions per patient) are required to detect a 30% increase in lesional MTR post-enhancement compared with placebo, whereas 48 subjects are required to detect a 50% increase in lesional MTR compared with placebo. Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents. PMID- 20350961 TI - Time domain and spectral domain optical coherence tomography in multiple sclerosis: a comparative cross-sectional study. AB - Conventional time domain optical coherence tomography has been established for the in vivo assessment of retinal axonal loss in multiple sclerosis. The innovative spectral domain imaging is superior to the conventional technique with respect to data acquisition speed, resolution and reproducibility. However, until now comparability of the two techniques has not been investigated in multiple sclerosis. In this study involving 55 multiple sclerosis patients, data obtained using both techniques (Stratus time domain optical coherence tomography and Cirrus spectral domain optical coherence tomography, Carl Zeiss Meditec) showed an excellent correlation (Pearson's r = 0.926, p < 0.001). However, owing to considerable differences in absolute retinal nerve fibre layer measurements (mean +/- standard deviation 8.1 microm +/- 6.2, range -12 to 23 microm), results from the two devices are not interchangeable. PMID- 20350962 TI - High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. AB - There are multiple sclerosis patients who suffer from an aggressive course of the disease with severe relapses and rapid accumulation of disability despite adequate treatment. In such cases high-dose immunoablation with autologous haematopoietic stem cell transplantation (ASCT) may be considered. Our objective was to report our experience with 26 multiple sclerosis patients treated with ASCT within the years 1998-2008. Twenty-six patients (Expanded Disability Status Scale 2.5-7.5 (median 6.0), multiple sclerosis duration 2-19 years (median 7)) with aggressive multiple sclerosis underwent autologous haematopoietic stem cell transplantation. Stem cells were mobilized by high-dose cyclophosphamide and granulocyte colony-stimulating factor, BEAM (carmustine, etoposide, cytarabine, melphalan) was used for immunoablation. Patients were evaluated at baseline and every six months post ASCT for adverse events and clinical outcome. Follow-up period was 11-132 months (median 66). Progression-free survival was calculated using the Kaplan- Meier method. At 3 and 6 years of follow-up 70.8% and 29.2% of patients respectively were free of progression. Patients with relapsing multiple sclerosis course, disease duration <5 years and age <35 years had a more favourable outcome. There was no death within 100 days after ASCT. We conclude that ASCT represents a viable and effective treatment option for aggressive multiple sclerosis. PMID- 20350963 TI - Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality. AB - BACKGROUND: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. METHODS: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor alpha (TNF-alpha) were used to evaluate inflammation. The patients were followed-up for 30 months. RESULTS: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-alpha levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) * (moderate/severe uremic pruritus) (all P < 0.05). CONCLUSION: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population. PMID- 20350964 TI - Commentary: Childhood abuse: new insights into its association with posttraumatic stress, suicidal ideation, and aggression. PMID- 20350965 TI - Sydenham chorea and Hashimoto thyroiditis: an unusual association. AB - Sydenham chorea is an immune-mediated neuropsychiatric disorder associated with group A beta-hemolytic streptococci infection. The authors present a 12-year-old female patient with Sydenham chorea and Hashimoto thyroiditis. Although Hashimoto thyroiditis has been associated with other autoimmune disorders, the association of Sydenham chorea and Hashimoto thyroiditis has not been previously reported. Immunological processes are suggested to be implicated in the pathogenesis of this association; however, the exact mechanism remains unclear. PMID- 20350966 TI - Screening of late-onset Pompe disease in a sample of Mexican patients with myopathies of unknown etiology: identification of a novel mutation in the acid alpha-glucosidase gene. AB - Pompe disease or glycogen-storage disease type 2 (GSD2, OMIM 232300) is an autosomal recessive disorder caused by mutations in the acid alpha-glucosidase gene. Late-onset GSD2 resembles some limb-girdle and Becker muscular dystrophies. The screening of GSD2 through the measurement of acid alpha-glucosidase activity in dried blood spots was applied to a selected sample of 5 Mexican patients with proximal myopathies of unknown etiology. Only 1 male patient showed a low level of acid alpha-glucosidase activity and a compound heterozygote genotype for the c.-32-13T>G splicing mutation present in most white late-onset Pompe disease cases and the novel mutation p.C558S. To our knowledge, this is the first report of a Mexican patient with late-onset GSD2. The identification of c.-32-13T>G in our patient could reflect the genetic contribution of European ancestry to the Mexican population. The enzymatic screening of GSD2 could be justified in patients with myopathies of unknown etiology. PMID- 20350967 TI - Comment on: Padmavathi et al. (2010) Chronic maternal dietary chromium restriction modulates visceral adiposity: probable underlying mechanisms. Diabetes;59:98-104. PMID- 20350972 TI - Pearls & Oy-sters: Large vessel ischemic stroke secondary to glioblastoma multiforme. PMID- 20350970 TI - Macrophage adiponectin expression improves insulin sensitivity and protects against inflammation and atherosclerosis. AB - OBJECTIVE: Adiponectin is one of several important metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice that specifically express the gene coding for human adiponectin in mouse macrophages using the human scavenger receptor A-I gene enhancer/promoter. METHODS AND RESULTS: Using this transgenic mouse model, we found that adiponectin expression was associated with reduced whole-animal body and fat-pad weight and an improved lipid accumulation in macrophages when these transgenic mice were fed with a high-fat diet. Moreover, these macrophage Ad-TG mice exhibit enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-a (both in the serum and in the metabolic active macrophage), adipose tissue, and skeletal muscle under the high fat diet condition. Additional studies demonstrated that these macrophage adiponectin transgenic animals exhibit reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with an LDL receptor deficient mouse model and were fed a high-fat diet. CONCLUSIONS: These results suggest that adiponectin expressed in macrophages can physiologically modulate metabolic activities in vivo by improving metabolism in distal tissues. The use of macrophages as carriers for adiponectin, a molecule with antidiabetes, anti inflammatory, and antiatherogenic properties, provides a novel and unique strategy for studying the mechanisms of adiponectin-mediated alterations in body metabolism in vivo. PMID- 20350973 TI - Teaching NeuroImages: neonatal intracerebral hemorrhage associated with aortic coarctation. PMID- 20350969 TI - Banting Lecture 2009: An unfinished journey: molecular pathogenesis to prevention of type 1A diabetes. PMID- 20350974 TI - Patient Page. Plasticity: teaching an old brain new tricks. PMID- 20350976 TI - Are white matter signal abnormalities clinically relevant? PMID- 20350977 TI - Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function. AB - OBJECTIVE: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). METHODS: We cross-sectionally examined 447 community dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. RESULTS: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (beta = -0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (beta = -0.237, p < 0.001), as well as regional FA scores of the frontal lobes (beta = -0.246, p < 0.001), the corona radiata (beta = -0.222, p < 0.001), and the corpus callosum (beta = -0.141, p = 0.016), in particular the genu (beta = -0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. CONCLUSION: These data suggest that low-grade inflammation as assessed by high sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function. PMID- 20350978 TI - Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. AB - BACKGROUND: Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS. METHODS: A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence. RESULTS: Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41 1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44-1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities. CONCLUSIONS: Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation. PMID- 20350979 TI - Persistent organochlorine pesticides in serum and risk of Parkinson disease. AB - BACKGROUND: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. METHODS: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. RESULTS: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97 1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. CONCLUSIONS: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings. PMID- 20350980 TI - Relationship between environmental factors and gray matter atrophy in refractory MTLE. AB - OBJECTIVE: To investigate clinical, neuropsychological, and MRI abnormalities (gray matter atrophy [GMA] and white matter atrophy [WMA]) in surgical mesial temporal lobe epilepsy (MTLE) patients with and without familial antecedent for epilepsy. METHODS: A cohort study including 69 operated patients with unilateral MTLE, divided into a group of 29 patients (mean age 35.8 +/- 10.4 years) with a negative family history (FH) of epilepsy and a group of 40 patients (32.8 +/- 10 years) with a positive FH. We performed voxel-based morphometry (VBM) on preoperative MRIs and investigated possible clinical and neuropsychological differences between the 2 groups. We also performed VBM and t tests to compare the patients' groups with normal controls. RESULTS: The negative-FH group had lower IQ scores (p = 0.004), performed poorer on the Boston Naming Test (p = 0.02) and on delayed recall (p = 0.03), and presented a more prominent asymmetry index of hippocampal volume (p = 0.04) and more frequent initial precipitating injuries (p = 0.023). VBM showed a more restricted pattern of GMA in the positive FH group and a more bilateral and widespread pattern of GMA in the negative-FH group, involving thalami, temporal, frontal, parietal, and occipital lobes. WMA was widespread and bilateral in both groups. CONCLUSIONS: The more widespread structural voxel-based morphometry abnormalities and worse IQ performance identified in the negative-family history (FH) group may result from a stronger environmental influence, including initial precipitating injuries. This is further support for the hypothesis that hippocampal sclerosis in mesial temporal lobe epilepsy with positive FH is determined by a stronger genetic predisposition with less influence of environmental factors compared with patients in the negative-FH group. PMID- 20350982 TI - Practice parameter: evaluation of the child with microcephaly (an evidence-based review): report of the quality standards subcommittee of the American Academy Of Neurology and the Practice Committee Of The Child Neurology Society. PMID- 20350981 TI - Equipoise among recanalization strategies. AB - Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach. PMID- 20350983 TI - Practice parameter: evaluation of the child with microcephaly (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. PMID- 20350984 TI - Practice parameter: evaluation of the child with microcephaly (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. PMID- 20350985 TI - Drug-eluting stents: a reappraisal. PMID- 20350986 TI - Low sex hormones in heart failure. PMID- 20350987 TI - Dynamic electrocardiographic changes in patients with arrhythmogenic right ventricular cardiomyopathy. AB - BACKGROUND AND OBJECTIVES: Electrocardiographic (ECG) abnormalities of depolarisation and repolarisation contribute to the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). The development of diagnostic ECG features were investigated in a genotyped cohort with ARVC to provide more sensitive markers of early disease. METHODS: T-wave inversion (TWI) in right precordial leads, epsilon waves, localised QRS prolongation greater than 110 ms in V1-V3 and QRS dispersion greater than 40 ms were analysed from 317 ECG from 68 genotyped patients (34 with disease-causing mutations) during follow-up of 34+/-28 months. RESULTS: 16 patients (23%) had changes during follow-up, with the appearance of new ECG abnormalities in seven (10%) and dynamic changes in nine (13%). Four developed new and persistent TWI and eight had dynamic TWI in right precordial leads. Three developed new and another three had dynamic epsilon waves. No changes were observed in 10 with and 58 patients without localised QRS prolongation and in six patients with and 61 without QRS dispersion greater than 40 ms. An additional patient with QRS dispersion at baseline had normal depolarisation dispersion during follow-up. None of the nine ARVC patients with dynamic ECG changes had major structural or functional right ventricular abnormalities, suggesting an early stage of the disease. CONCLUSIONS: New or dynamic ECG changes were observed in 23%. This underscores the importance of serial ECG in the diagnosis of individuals at risk of ARVC, in whom potentially lethal arrhythmia may develop before major abnormalities are detectable with conventional imaging. PMID- 20350988 TI - Early treatment with clarithromycin attenuates rat autoimmune myocarditis via inhibition of matrix metalloproteinase activity. AB - BACKGROUND: Matrix metalloproteinase (MMP) activity is upregulated in the hearts with myocarditis, and its activation contributes to the changes in left ventricular function. A major macrolide antibiotic, clarithromycin (CAM), has many biological functions including MMP regulation. However, little is known about the effect of CAM in myocarditis via MMPs. OBJECTIVE: To clarify the role of MMPs regulated by CAM in the progression of myocarditis. Design CAM was given to experimental rats with autoimmune myocarditis (EAM) from day -7 to day 21 (early treated group, n=6) or from day 1 to day 21 (late treated group, n=6) twice a day. RESULTS: Although the non-treated rats showed blood pressure decline and impaired cardiac function, early CAM treatment prevented this progression. Pathologically, severe myocardial cell infiltration (30.5+/-4.2%) and fibrosis (32.2+/-1.1%) were detected in the non-treated group, while early CAM treatment significantly suppressed these changes (infiltration 6.5+/-0.2%, fibrosis 5.9+/ 3.9%). Zymography showed that non-treated EAM resulted in enhanced ventricular activities of MMP-9, while early CAM treatment reduced the alteration. However, late CAM treatment was less effective than the early treatment. CONCLUSIONS: Early CAM treatment is effective to attenuate myocarditis by suppressing MMP-9. PMID- 20350989 TI - Progression of preclinical diastolic dysfunction to the development of symptoms. AB - BACKGROUND: Preclinical diastolic dysfunction (PDD) has been defined as subjects with normal systolic function, diastolic dysfunction but no symptoms of heart failure (HF). The clinical phenotype and natural history of the syndrome remains poorly defined. This study's objective was to determine the clinical phenotype and progression to HF in a group of patients with normal systolic function and moderate or severe diastolic dysfunction as determinate by Doppler criteria without any clinical diagnosis of HF according to the Framingham criteria or any symptoms of HF, specifically dyspnoea, oedema or fatigue at the time of echocardiography. METHODS: The authors used resources of the Mayo Clinic echocardiography database to consecutively select among patients who had an echocardiogram in 2005, a cohort with moderate or severe diastolic dysfunction by Doppler criteria and EF >or=50%. Patients could not have a diagnosis of HF, or any HF symptoms-specifically dyspnoea, oedema or fatigue-at the time of echocardiography; nor grade 3 or greater valvular dysfunction (except tricuspid valve). A total of 82 patients had their medical chart reviewed. Primary endpoint was the time to the development of (1) HF according to the Framingham criteria or (2) any symptoms of dyspnoea, oedema or fatigue. RESULTS: The mean age of the cohort of PDD subjects was 69+/-10 years with a female (67%) preponderance. Presence of hypertension was 76%, coronary artery disease was 29%, paroxysmal atrial fibrillation was 26%, estimated creatinine clearance <60 ml/min was 51%. The 2-year cumulative probability of development of HF according to the Framingham criteria was 1.9%; however, the 2-year cumulative probability of development of any symptoms was 31.1%. The 2-year cumulative probability for cardiac hospitalisation was 21.2%. Peripheral vascular disease and hypertension were independently associated with increased likelihood for the development of symptoms. CONCLUSION: The study demonstrates that hypertension, hyperlipidaemia, CAD and renal dysfunction are prevalent in patients with PDD. More importantly, although the progression to the development of clinical HF over 2 years was low, there was a moderate degree of progression to development of symptoms and cardiac hospitalisations over 2 years. Based on the finding that only PVD and hypertension were independently associated with the progression to the development of symptoms in subject with PDD, the authors speculate that ventricular-arterial interaction may be important to the progression of diastolic dysfunction to the development of symptoms. PMID- 20350990 TI - Potentially detrimental cardiovascular effects of oxygen in patients with chronic left ventricular systolic dysfunction. AB - BACKGROUND: Although the haemodynamic effects of oxygen in healthy subjects are well documented, there have been no well-controlled studies of the effects of oxygen in patients with heart failure (HF). AIMS: To non-invasively evaluate haemodynamic and neurohumoral effects of oxygen in patients with HF at rest. METHODS AND RESULTS: 13 men with heart failure and left ventricular systolic dysfunction (LVSD) were randomised in a double-blind, placebo-controlled, crossover trial to receive medical air or oxygen (40% and high concentration via Hudson non-rebreathing mask). Haemodynamic measurements were made with applanation tonometry, impedance cardiography and venous occlusion plethysmography. Plasma C-terminal B-type natriuretic peptide and A-type natriuretic peptide were measured. Data were analysed with paired t tests. Cardiac output fell by -0.58 (0.62) l/min on high-flow oxygen compared with -0.02 (0.58) l/min on air, p=0.031. Oxygen caused a reduction in heart rate (-4.02 (4.21) vs 0.41 (5.35) beats/min, respectively, p=0.021) and a trend towards increased systemic vascular resistance (875 (1174) vs 235 (321) dyne/s/m(5), p=0.050). Oxygen led to a paradoxical increase in forearm blood flow (0.513 (0.391) vs 0.024 (0.246) ml/min/100 ml forearm volume on air, p=0.01). Natriuretic peptides were unchanged with oxygen. CONCLUSIONS: High-concentration inhaled oxygen has significant haemodynamic effects in patients with LVSD and mild HF. Such effects may be detrimental in patients with decompensated HF. PMID- 20350991 TI - Gender differences in clinical presentation and surgical outcome of aortic stenosis. AB - BACKGROUND: Little is known about the gender differences of patients undergoing aortic valve replacement (AVR) for isolated severe aortic stenosis. METHODS AND RESULTS: 408 consecutive patients (215 women and 193 men; p=0.9) were analysed. At presentation, women were older (73.7+/-9.3 years vs men 66.5+/-11.5 years; p<0.001), more symptomatic (New York Heart Association (NYHA) class: women 2.3+/ 0.7 vs men 2.0+/-0.65; p<0.001), and presented with smaller valve areas (women 0.6+/-0.2 cm(2) vs men 0.7+/-0.2 cm(2); p<0.001) and higher mean pressure gradients (women 67.3+/-19.2 mm Hg vs men 62.2+/-20.0 mm Hg, p=0.001). Despite older age and more advanced disease in women, operative mortality did not differ. Survival after AVR by Kaplan-Meier analysis tended to be even better in women (92.8%, 89.8%, 81.4% vs men 89.1%, 86.6%, 76.3% at 1, 2 and 5 years, p=0.31). After division into age quintiles, the outcome of women was significantly better in patients older than 79 years (p=0.005). After adjustment for clinical characteristics, gender did not predict operative mortality and late outcome. Despite physical improvement in both groups after surgery, women remained more symptomatic (NYHA class: women 1.6+/-0.7 vs men 1.3+/-0.4; p=0.001). CONCLUSION: Although women referred to AVR are older and more symptomatic, operative and long term mortality are not increased. In the oldest age group of 79 years and older, women even have a better outcome, presumably due to a longer mean life expectancy. PMID- 20350992 TI - Intravenous administration of flecainide or propafenone in patients with recent onset atrial fibrillation does not predict adverse effects during 'pill-in-the pocket' treatment. AB - BACKGROUND: Pill-in-the-pocket treatment should be prescribed only if the administration of a loading oral dose of flecainide or propafenone has been proved safe in hospital, since major adverse effects have been reported in 5% of patients during in-hospital treatment. However, in emergency rooms, the oral administration of these drugs for the conversion of atrial fibrillation (AF) is very rarely used because it is time consuming. Objective To investigate whether tolerance to intravenous administration of flecainide or propafenone might predict the safety of pill-in-the-pocket treatment-the out-of-hospital self administration of these drugs after the onset of palpitations-in patients with AF of recent onset. METHODS: One hundred and twenty-two patients with AF of recent onset who were successfully treated (conversion of AF within 2 h without major adverse effects) in hospital with intravenous flecainide or propafenone were discharged on pill-in-the-pocket treatment. RESULTS: During a mean follow-up of 11+/-4 months, 79 patients self-treated 213 arrhythmic episodes; treatment was successful in 201 episodes (94%). Major adverse events occurred in five patients (6%) and in four (5%) of these during the first oral treatment (one syncope, two presyncope, one sinus arrest). No patient reported symptoms attributable to bradyarrhythmia or hypotension during the self-treatment of arrhythmic recurrences when the first oral treatment was not accompanied by any major adverse effects. The study was prematurely terminated because of the high incidence of major adverse effects during the first out-of-hospital treatment. CONCLUSION: The patient's tolerance of intravenous administration of flecainide or propafenone does not seem to predict adverse effects during out-of-hospital self-administration of these drugs. PMID- 20350993 TI - Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis. PMID- 20350994 TI - Frailty: the great confounder, the great forgotten. PMID- 20350995 TI - Daily variability in waist circumference. PMID- 20350997 TI - Pulmonary hypertension: updated classification and management of pulmonary hypertension. PMID- 20350998 TI - Non-invasive imaging: Non-invasive assessment of coronary artery disease in diabetes. PMID- 20351000 TI - Technical report--racial and ethnic disparities in the health and health care of children. AB - OBJECTIVE: This technical report reviews and synthesizes the published literature on racial/ethnic disparities in children's health and health care. METHODS: A systematic review of the literature was conducted for articles published between 1950 and March 2007. Inclusion criteria were peer-reviewed, original research articles in English on racial/ethnic disparities in the health and health care of US children. Search terms used included "child," "disparities," and the Index Medicus terms for each racial/ethnic minority group. RESULTS: Of 781 articles initially reviewed, 111 met inclusion criteria and constituted the final database. Review of the literature revealed that racial/ethnic disparities in children's health and health care are quite extensive, pervasive, and persistent. Disparities were noted across the spectrum of health and health care, including in mortality rates, access to care and use of services, prevention and population health, health status, adolescent health, chronic diseases, special health care needs, quality of care, and organ transplantation. Mortality-rate disparities were noted for children in all 4 major US racial/ethnic minority groups, including substantially greater risks than white children of all-cause mortality; death from drowning, from acute lymphoblastic leukemia, and after congenital heart defect surgery; and an earlier median age at death for those with Down syndrome and congenital heart defects. Certain methodologic flaws were commonly observed among excluded studies, including failure to evaluate children separately from adults (22%), combining all nonwhite children into 1 group (9%), and failure to provide a white comparison group (8%). Among studies in the final database, 22% did not perform multivariable or stratified analyses to ensure that disparities persisted after adjustment for potential confounders. CONCLUSIONS: Racial/ethnic disparities in children's health and health care are extensive, pervasive, and persistent, and occur across the spectrum of health and health care. Methodologic flaws were identified in how such disparities are sometimes documented and analyzed. Optimal health and health care for all children will require recognition of disparities as pervasive problems, methodologically sound disparities studies, and rigorous evaluation of disparities interventions. PMID- 20351001 TI - The experiences of children enrolled in pediatric oncology research: implications for assent. AB - BACKGROUND: Most children with cancer enroll in clinical research trials. Whenever possible, children must provide their assent before enrolling in research studies. We studied what children aged 7 to 18 with cancer understand about research, their research-related treatment, and their preferences for inclusion in decision-making. PROCEDURE: Thirty-seven face-to-face, audiorecorded interviews using a novel, semi-structured tool, the quality-of-assent instrument, were conducted. Exploratory univariate and bivariate analyses of the quantitative data elucidated patterns and trends of understanding and preferences. RESULTS: Nineteen of the 37 children (51%) did not know or recall that their treatment was considered research, and 19 of 22 (86%) did not understand their doctor when he or she discussed the trial. More children enrolled in trials to help future children with cancer (27 of 37 [73%]), than to get better personally (22 of 37 [60%]). Irrespective of age, children with Hodgkin's disease, germ-cell tumors, and leukemia had significantly greater research awareness and appreciation than children with other cancers (P = .019 and P < .001, respectively). Although all children wanted to be involved in decision-making, 18 of 37 (49%) did not have or recall having a role in deciding to enroll in their trial, and 14 of 37 (38%) did not feel free to dissent to trial enrollment. Only 4 of 37 children (11%) discussed increased decision-making roles with parents, and only 7 of 37 (19%) discussed them with their doctors. CONCLUSIONS: Most children have limited understanding of research despite physicians' explanations. Many children reported that they feel minimally involved in the decision to enroll in clinical trials. Tools to assist investigators ascertain that children understand what they are agreeing to when they assent to research and to determine their preferences for inclusion in research may help make assent more meaningful. PMID- 20350999 TI - Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. AB - The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era. PMID- 20351002 TI - Risk factors and estimation tool for death among extremely premature infants: a national study. AB - OBJECTIVES: The goals were to assess risk factors and mortality rate changes over time and to develop simple estimates of mortality rates for specific groups of infants at 23 to 26 weeks of gestation. METHODS: Data from the Israel national very low birth weight infant database on 3768 infants born in 1995-2006 with gestational ages (GAs) of 23 to 26 weeks were evaluated, and we developed a tool for estimating infants' mortality rates. RESULTS: Major factors associated with death were GA, gender-specific birth weight percentile, prenatal steroid therapy, and multiple births. There was a steady decrease in mortality rates for all GAs during the study period. In 2004-2006, mortality rates before discharge were 89%, 67%, 46%, and 26% for infants with GAs of 23, 24, 25, and 26 weeks, respectively. Estimated mortality rates were calculated as the sum of the percentages determined for each of 4 parameters, as follows: GA of 26, 25, 24, or 23 weeks, 0%, 17%, 34%, and 51%, respectively (P < .001); birth weight percentile of >75th, 25th to 75th, or <25th, 0%, 16%, and 32%, respectively (P < .001); no prenatal steroid treatment, +22% (P < .001); multiple birth, +7% (P = .1). Estimated mortality rates for the 48 subgroups of infants ranged from 0% to 100% and correlated well with observed rates (intraclass correlation coefficient: 0.89). CONCLUSION: Mortality rates for infants born at 23 to 26 weeks of gestation could be estimated simply on the basis of GA, gender-specific birth weight quartiles, prenatal corticosteroid therapy, and multiple births. PMID- 20351003 TI - Benign neonatal sleep myoclonus: a review of the literature. AB - OBJECTIVE: Neurologically normal term infants sometimes present with repetitive, rhythmic myoclonic jerks that occur during sleep. The condition, which is traditionally resolved by 3 months of age with no sequelae, is termed benign neonatal sleep myoclonus. The goal of this review was to synthesize the published literature on benign neonatal sleep myoclonus. METHODS: The US National Library of Medicine database and the Web-based search engine Google, through June 2009, were used as data sources. All articles published after the seminal description in 1982 as full-length articles or letters were collected. Reports that were published in languages other than English, French, German, Italian, Portuguese, or Spanish were not considered. RESULTS: We included 24 reports in which 164 term born (96%) or near-term-born (4%) infants were described. Neonatal sleep myoclonus occurred in all sleep stages, disappeared after arousal, and was induced by rocking the infant or repetitive sound stimuli. Furthermore, in affected infants, jerks stopped or even worsened by holding the limbs or on medication with antiepileptic drugs. Finally, benign neonatal sleep myoclonus did not resolve by 3 months of age in one-third of the infants. CONCLUSIONS: This review provides new insights into the clinical features and natural course of benign neonatal sleep myoclonus. The most significant limitation of the review comes from the small number of reported cases. PMID- 20351004 TI - Head injury depth as an indicator of causes and mechanisms. AB - OBJECTIVE: The goal was to measure differences in the causes, mechanisms, acute clinical presentations, injuries, and outcomes of children <36 months of age with varying "greatest depths" of acute cranial injury. METHODS: Children <36 months of age who were hospitalized with acute head trauma were recruited at multiple sites. Clinical and imaging data were collected, and caregivers underwent scripted interviews. Neurodevelopmental evaluations were completed 6 months after injury. Head trauma causes were categorized independently, and subject groups with varying greatest depths of injury were compared. RESULTS: Fifty-four subjects were enrolled at 9 sites. Twenty-seven subjects underwent follow-up neurodevelopmental assessments 6 months after injury. Greatest depth of visible injury was categorized as scalp, skull, or epidural for 20 subjects, subarachnoid or subdural for 13, cortical for 10, and subcortical for 11. Compared with subjects with more-superficial injuries, subjects with subcortical injuries more frequently had been abused (odds ratio [OR]: 35.6; P < .001), more frequently demonstrated inertial injuries (P < .001), more frequently manifested acute respiratory (OR: 43.9; P < .001) and/or circulatory (OR: 60.0; P < .001) compromise, acute encephalopathy (OR: 28.5; P = .003), prolonged impairments of consciousness (OR: 8.4; P = .002), interhemispheric subdural hemorrhage (OR: 10.1; P = .019), and bilateral brain hypoxia, ischemia, or swelling (OR: 241.6; P < .001), and had lower Mental Developmental Index (P = .006) and Gross Motor Quotient (P < .001) scores 6 months after injury. CONCLUSION: For children <3 years of age, head injury depth is a useful indicator of injury causes and mechanisms. PMID- 20351005 TI - Gastroesophageal reflux and asthma in children: a systematic review. AB - CONTEXT: The relationship between gastroesophageal reflux disease (GERD) and asthma in children has been investigated; however, the nature of the association (if any) between these 2 conditions is unclear. OBJECTIVE: We performed a systematic review of the literature to examine the association between GERD and asthma in children. METHODS: A search of the medical literature was conducted by using PubMed and Embase (1966 through December 2008). Full-length articles in English that described at least 20 subjects younger than 18 years were included if they reported the prevalence of GERD (symptoms, pH studies, endoscopy/histology) in individuals with asthma or the prevalence of asthma in individuals with GERD. We calculated pooled odds ratios from studies that examined control groups, and we pooled prevalence estimates from all studies. RESULTS: A total of 20 articles that described 5706 patients fulfilled the inclusion and exclusion criteria. Seventeen studies used objective methods for documenting reflux (eg, pH probe, contrast imaging, impedance, esophagogastroduodenoscopy), 2 studies relied on symptom-based questionnaires, and 1 study used diagnostic codes. Most studies (n = 19) examined the prevalence of GERD in 3726 individuals with asthma and reported highly variable estimates (19.3%-80.0%) and a pooled average of 22.8% with GERD symptoms, 62.9% of 789 patients with abnormal esophageal pH, and 34.8% of 89 patients with esophagitis. Only 5 studies included controls and enrolled 1314 case-patients with asthma and 2434 controls without asthma. The average prevalence of GERD was 22.0% in asthma cases and 4.8% in controls (pooled odds ratio: 5.6 [95% confidence interval: 4.3 6.9]). CONCLUSIONS: There is a possible association between GERD and asthma in pediatric patients seen with asthma in referral settings. However, because of methodologic limitations of existing studies, the paucity of population-based studies, and a lack of longitudinal studies, several aspects of this association are unclear. PMID- 20351006 TI - Changes in neonatal transfusion practice after dissemination of neonatal recommendations. AB - OBJECTIVE: To evaluate the change in neonatal transfusion practices after the introduction of national recommendations for transfusion of blood products to neonates in 2006. METHODS: A questionnaire-based survey on neonatal transfusion practice of 79 Italian NICUs was completed in 2008. Results were compared with those obtained from a previous national Italian neonatal transfusion-practice survey performed in 2001. RESULTS: Responses were received from 62 of 79 (78.5%) neonatal units. Prophylaxis for transfusion-transmitted cytomegalovirus infection in 2001 and 2008 had been performed in 96.8% and 98.4% of NICUs, respectively. Filter leukoreduction of red blood cell donor units was preferred over cytomegalovirus antibody testing to obtain cytomegalovirus-safe blood components. Prophylaxis for graft-versus-host disease increased from being performed at 61.3% of neonatal units in 2001 to 77.4% in 2008 (P = .08, Pearson chi(2)), whereas usage of dedicated red blood cell donor units (paedipack system), permitting multiple transfusions from the same unit, improved from 53.2% to 82.2% (P = .001, Pearson chi(2)). The 2008 survey documented a continuation of wide variability in transfusion practice for fresh-frozen plasma and platelet concentrates. CONCLUSIONS: This nation-wide Italian self-report survey highlighted improvements in NICU transfusion practice after the neonatal recommendations issued in 2006. Prophylaxis for transfusion-transmitted cytomegalovirus infection continued with nearly total adherence to national recommendations, and both prophylaxis for graft-versus-host disease and paedipack-system usage suggested a trend of improvement of adherence rates. The continuing wide diversity observed among neonatal units in fresh-frozen plasma and platelet-concentrate transfusion practice may indicate a lack of acceptable criteria for the administration of these blood products. PMID- 20351007 TI - Medicaid, underinsurance, and the dawn of an era for children's coverage. PMID- 20351009 TI - Policy statement--health equity and children's rights. AB - Many children in the United States fail to reach their full health and developmental potential. Disparities in their health and well-being result from the complex interplay of multiple social and environmental determinants that are not adequately addressed by current standards of pediatric practice or public policy. Integrating the principles and practice of child health equity-children's rights, social justice, human capital investment, and health equity ethics-into pediatrics will address the root causes of child health disparities. Promoting the principles and practice of equity-based clinical care, child advocacy, and child- and family-centered public policy will help to ensure that social and environmental determinants contribute positively to the health and well-being of children. The American Academy of Pediatrics and pediatricians can move the national focus from documenting child health disparities to advancing the principles and practice of child health equity and, in so doing, influence the worldwide practice of pediatrics and child health. All pediatricians, including primary care practitioners and medical and surgical subspecialists, can incorporate these principles into their practice of pediatrics and child health. Integration of these principles into competency-based training and board certification will secure their assimilation into all levels of pediatric practice. PMID- 20351008 TI - Policy statement--emergency information forms and emergency preparedness for children with special health care needs. AB - Children with chronic medical conditions rely on complex management plans for problems that cause them to be at increased risk for suboptimal outcomes in emergency situations. The emergency information form (EIF) is a medical summary that describes medical condition(s), medications, and special health care needs to inform health care providers of a child's special health conditions and needs so that optimal emergency medical care can be provided. This statement describes updates to EIFs, including computerization of the EIF, expanding the potential benefits of the EIF, quality-improvement programs using the EIF, the EIF as a central repository, and facilitating emergency preparedness in disaster management and drills by using the EIF. PMID- 20351010 TI - Clinical report--guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. AB - The proper ethical conduct of studies to evaluate drugs in children is of paramount importance to all those involved in these types of studies. This report is an updated revision to the previously published guidelines from the American Academy of Pediatrics in 1995. Since the previous publication, there have been great strides made in the science and ethics of studying drugs in children. There have also been numerous legislative and regulatory advancements that have promoted the study of drugs in children while simultaneously allowing for the protection of this particularly vulnerable group. This report summarizes these changes and advances and provides a framework from which to guide and monitor the ethical conduct of studies to evaluate drugs in children. PMID- 20351011 TI - Policy statement--pediatric organ donation and transplantation. AB - Pediatric organ donation and organ transplantation can have a significant life extending benefit to the young recipients of these organs and a high emotional impact on donor and recipient families. Pediatricians, pediatric medical specialists, and pediatric transplant surgeons need to be better acquainted with evolving national strategies that involve organ procurement and organ transplantation to help acquaint families with the benefits and risks of organ donation and transplantation. Efforts of pediatric professionals are needed to shape public policies to provide a system in which procurement, distribution, and cost are fair and equitable to children and adults. Major issues of concern are availability of and access to donor organs; oversight and control of the process; pediatric medical and surgical consultation and continued care throughout the organ-donation and transplantation process; ethical, social, financial, and follow-up issues; insurance-coverage issues; and public awareness of the need for organ donors of all ages. PMID- 20351012 TI - 25-hydroxyvitamin D status of healthy, low-income, minority children in Atlanta, Georgia. AB - OBJECTIVES: The goals were to determine the prevalence of vitamin D deficiency among minority children in a southern US city, to examine differences in serum 25 hydroxyvitamin D levels between non-Hispanic black and Hispanic children, and to determine dietary sources of vitamin D. METHODS: Low-income, minority children (N = 290; mean age: 2.5 +/- 1.2 years) were recruited during well-child clinic visits. Serum 25-hydroxyvitamin D and calcium levels were measured and dietary information was assessed. RESULTS: The mean 25-hydroxyvitamin D(3) level was 26.2 +/- 7.6 ng/mL, whereas 25-hydroxyvitamin D(2) was not detected. Overall, 22.3% of children had deficient serum 25-hydroxyvitamin D(3) levels (< or =20 ng/mL), 73.6% had less-than-optimal serum 25-hydroxyvitamin D levels (< or =30 ng/mL), and 1.4% had low serum calcium levels (< or =9 mg/dL). A significantly larger proportion of non-Hispanic black children, compared with Hispanic children, had vitamin D deficiency (26% vs 18%; P < .05). Age and season of recruitment were significantly associated with vitamin D deficiency and low serum calcium levels. Older children (> or =3 years) were less likely to have vitamin D deficiency (odds ratio [OR]: 0.89 [95% confidence interval [CI]: 0.81-0.96]; P < .001). Study enrollment during spring and summer reduced the likelihood of vitamin D deficiency by approximately 20% (spring, OR: 0.85 [95% CI: 0.73-0.98]; P = .03; summer, OR: 0.82 [95% CI: 0.73-0.92]; P < .01). Fortified milk provided most dietary vitamin D (62%), with Hispanic children reporting greater intake. CONCLUSIONS: Suboptimal vitamin D status was common among apparently healthy, low income, minority children. Age and season were significant predictors of vitamin D deficiency. PMID- 20351013 TI - Evidence-based treatment decisions for extremely preterm newborns. PMID- 20351014 TI - Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. AB - Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid l-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor alpha, interleukin-1beta, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain. PMID- 20351015 TI - Self-expanding mini-cannula for remote perfusion with pediatric scenarios. AB - The aim of this report is to address the benefits of the minimal invasive venous drainage in a pediatric cardio surgical scenario. Juvenile bovine experiments (67.4+/-11 kg) were performed. The right atrium was cannulated in a trans-jugular way by using the self-expandable (Smart Stat, 12/20F, 430 mm) venous cannula (Smartcannula LLC, Lausanne, Switzerland) vs. a 14F 250 mm (Polystan Lighthouse) standard pediatric venous cannula. Establishing the cardiopulmonary bypass (CPB), the blood flows were assessed for 20 mmHg, 30 mmHg and 40 mmHg of driving pressure. Venous drainage (flow in l/min) at 20 mmHg, 30 mmHg, and 40 mmHg drainage load was 0.26+/-0.1, 0.35+/-0.2 and 0.28+/-0.08 for the 14F standard vs. 1.31+/-0.22, 1.35+/-0.24 and 1.9+/-0.2 for the Smart Stat 12/20F cannula. The 43 cm self-expanding 12/20F Smartcannula outperforms the 14F standard cannula. The results described herein allow us to conclude that usage of the self-expanding Smartcannula also in the pediatric patients improves the flow and the drainage capacity, avoiding the insufficient and excessive drainage. We believe that similar results may be expected in the clinical settings. PMID- 20351016 TI - Guide wire fracture during percutaneous transluminal coronary angioplasty: possible causes and management. AB - A 46-year-old woman underwent diagnostic coronary angiography in our institution due to a myocardial ischemia following a dobutamine echo-stress test. The patient showed critical stenosis of the left anterior descending (LAD) artery involving the ostium of a large diagonal branch. The planned treatment of coronary bifurcation by percutaneous coronary intervention (PCI) was direct stenting of the main branch with 'jailed' wire technique to protect the side branch, provisional T stenting of the side branch, and final kissing balloon inflation. After successful stent implantation in the LAD, the 'jailed' wire fractured during withdrawal: the distal part of the fragment was trapped in the side branch, and the proximal one was knotted in the LAD, left main coronary and the aortic bulb. We decided not to retrieve the fragment by snare, and we planned heart surgery to safely retrieve the fragment and bypass the side branch not treated by percutaneous coronary interventions. Angiographic control nine months after surgery showed non in-stent restenosis; patient is alive and event-free at 18 months' clinical follow-up. In conclusion, percutaneous management of particularly complex bifurcational lesions may be associated with procedural risks; accordingly, it is important to consider and be ready for a rescue surgical revascularization. PMID- 20351017 TI - Definitive diagnosis of multiple myeloma from rib specimens resected at thoracotomy in a patient with lung cancer. AB - A 52-year-old man noted large amounts of bloody sputum and visited our hospital. Chest X-ray showed a mass shadow in the right upper lung field. He was diagnosed with squamous cell carcinoma (SCC). Although he was not aware of symptoms other than the bloody sputum, his blood chemistry showed a high total serum protein level of 10.6 g/dl. Further analysis of serum immunoglobulin revealed a markedly high immunoglobulin G (IgG) level, but an abnormally low level of immunoglobulin A (IgA) and immunoglobulin M (IgM). Serum immunoelectrophoresis detected IgG lambda monoclonal protein; therefore, we suspected the coexistence of multiple myeloma, amyloidosis, benign macroglobulinemia, or benign monoclonal gammopathy. Since the patient continued to expectorate large amounts of bloody sputum every day, and his anemia progressed, right upper lobectomy and lymph node dissection were performed on a semi-emergent basis without preoperative bone marrow examination. On thoracotomy at the level of the fifth intercostal space, the fifth and sixth ribs were partially resected posteriorly, and the resected ribs were submitted for pathological examination. The postoperative pathological diagnosis was SCC of the lung (p-T2N0M0, stage IB). Pathological examination of the ribs revealed IgG-lambda myeloma. Herein, we report a patient with lung cancer in whom multiple myeloma was definitively diagnosed from rib specimens resected at thoracotomy. PMID- 20351018 TI - Tricuspid valve replacement with a fresh antibiotic preserved tricuspid homograft. AB - Prosthetic replacement of valves in children is limited by size constraints of the prosthesis and lack of growth potential. In specific situations like infective endocarditis, valve preservation is near impossible and in such instances alternatives are hard to get. Furthermore, in the tricuspid position the long-term results of both mechanical and bioprosthesis are not optimal. We used an innovative method in a small boy with tricuspid valve endocarditis by using a tricuspid homograft in the tricuspid position. PMID- 20351019 TI - Temperature stress and plant sexual reproduction: uncovering the weakest links. AB - The reproductive (gametophytic) phase in flowering plants is often highly sensitive to hot or cold temperature stresses, with even a single hot day or cold night sometimes being fatal to reproductive success. This review describes studies of temperature stress on several crop plants, which suggest that pollen development and fertilization may often be the most sensitive reproductive stage. Transcriptome and proteomic studies on several plant species are beginning to identify stress response pathways that function during pollen development. An example is provided here of genotypic differences in the reproductive stress tolerance between two ecotypes of Arabidopsis thaliana Columbia (Col) and Hilversum (Hi-0), when reproducing under conditions of hot days and cold nights. Hi-0 exhibited a more severe reduction in seed set, correlated with a reduction in pollen tube growth potential and tropism defects. Hi-0 thus provides an Arabidopsis model to investigate strategies for improved stress tolerance in pollen. Understanding how different plants cope with stress during reproductive development offers the potential to identify genetic traits that could be manipulated to improve temperature tolerance in selected crop species being cultivated in marginal climates. PMID- 20351021 TI - High-level visual object representations are constrained by position. AB - It is widely assumed that high-level visual object representations are position independent (or invariant). While there is sensitivity to position in high-level object-selective cortex, position and object identity are thought to be encoded independently in the population response such that position information is available across objects and object information is available across positions. Contrary to this view, we show, with both behavior and neuroimaging, that visual object representations are position-dependent (tied to limited portions of the visual field). Behaviorally, we show that the effect of priming an object was greatly reduced with any change in position (within- or between-hemifields), indicating nonoverlapping representations of the same object across different positions. Furthermore, using neuroimaging, we show that object-selective cortex is not only highly sensitive to object position but also the ability to differentiate objects based on its response is greatly reduced across different positions, consistent with the observed behavior and the receptive field properties observed in macaque object-selective neurons. Thus, even at the population level, the object information available in response of object selective cortex is constrained by position. We conclude that even high-level visual object representations are position-dependent. PMID- 20351022 TI - Self-esteem modulates medial prefrontal cortical responses to evaluative social feedback. AB - Self-esteem is a facet of personality that influences perception of social standing and modulates the salience of social acceptance and rejection. As such, self-esteem may bias neural responses to positive and negative social feedback across individuals. During functional magnetic resonance imaging scanning, participants (n = 42) engaged in a social evaluation task whereby they ostensibly received feedback from peers indicating they were liked or disliked. Results demonstrated that individuals with low self-esteem believed that they received less positive feedback from others and showed enhanced activity to positive versus negative social feedback in the ventral anterior cingulate cortex/medial prefrontal cortex (vACC/mPFC). By contrast, vACC/mPFC activity was insensitive to positive versus negative feedback in individuals with high self-esteem, and these individuals consistently overestimated the amount of positive feedback received from peers. Voxelwise analyses supported these findings; lower self-esteem predicted a linear increase in vACC/mPFC response to positive versus negative social feedback. Taken together, the present findings propose a functional role for the vACC/mPFC in representing the salience of social feedback and shaping perceptions of relative social standing. PMID- 20351023 TI - Obesity and risk of subsequent hospitalisation with pneumonia. AB - Obesity may be associated with increased risk of pneumonia, but available data on this relationship are sparse and inconsistent. We followed a prospective cohort of 22,578 males and 25,973 females from the Danish Diet, Cancer and Health Study, aged 50-64 yrs and free from major chronic diseases at baseline (1993-1997), for first-time hospitalisation with pneumonia (median follow-up 12 yrs). Compared with males of normal weight, adjusted hazard ratios (HRs) for pneumonia were 1.4 (95% CI 1.2-1.7) for males with moderate obesity (body mass index (BMI) 30.0-34.9 kg.m-2), and 2.0 (95% CI 1.4-2.8) for males with severe obesity (BMI >= 35.0 kg.m 2), controlling for lifestyle and educational variables. Among females the associations were weaker, with adjusted HRs of 0.8 (95% CI 0.6-1.0) for moderate obesity, and 1.2 (95% CI 0.8-1.6) for severe obesity. Adjustment for major chronic diseases diagnosed during follow-up eliminated the associations between obesity and pneumonia risk. Obesity is associated with higher risk of hospitalisation with pneumonia among males but not among females, which is apparently explained by occurrence of other chronic diseases. PMID- 20351024 TI - An experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated piglets. AB - The objectives of the study were to validate a model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in ventilated piglets and to study the time-course of biological markers and histopathological changes. 12 piglets were intubated and inoculated with 15 mL of a suspension of 10(6) colony forming units of MRSA in every lobe through the bronchoscope channel. The piglets were ventilated for 12 h (n = 6) and 24 h (n = 6). Clinical parameters were assessed every 6 h and pro-inflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL) at baseline and sacrifice. Histopathology of each lobe and cultures from blood, lungs and BAL were performed. Animals developed histopathological evidence of pneumonia at necropsy. At 12 h, pneumonia was present in all animals and was severe pneumonia at 24 h. Microbiological studies confirmed the presence of MRSA. A significant increase in interleukin (IL)-6, IL 8 and tumour necrosis factor-alpha values was seen in BAL at 24 h and IL-6 at 12 h. In serum, only IL-6 levels had increased significantly at 24 h. In ventilated piglets, bronchoscopic inoculation of MRSA induces pneumonia at 12 h and severe pneumonia at 24 h. This severity was associated with a corresponding increase in systemic and local inflammatory response. PMID- 20351025 TI - Deposition and metabolism of inhaled ciclesonide in the human lung. AB - Ciclesonide is an inhaled corticosteroid, administered as a prodrug via a metered dose inhaler. Following deposition in the lung, ciclesonide is hydrolysed by esterases to form the pharmacologically active metabolite desisobutyryl ciclesonide (des-CIC). Formation of des-CIC, as well as reversible esterification of des-CIC with fatty acids, has been demonstrated in vitro. The aim of this study was to investigate the in vivo metabolism of ciclesonide in the human lung. This single-dose, open-label, nonrandomised study was performed in 20 patients undergoing planned lung surgery for treatment of malignant pulmonary lesions. Patients inhaled a single dose of 1,280 MUg ciclesonide at various time-points between 2 and 24 h prior to lung tissue resection. The concentration of ciclesonide, des-CIC and fatty acid conjugates of des-CIC in tissue samples was determined. Serum samples for pharmacokinetic analysis were taken at several time points after inhalation. The pharmacokinetics in serum indicated that the inhalation by the patients was adequate. Metabolites (des-CIC, des-CIC oleate and des-CIC palmitate) were detected in the resected central and peripheral lung tissues. A substantial portion of ciclesonide was already activated to des-CIC at the first time-point of tissue analysis. Activation of ciclesonide and formation of des-CIC fatty acid conjugates was confirmed in vivo in the human lung. PMID- 20351026 TI - Changes in the FEV1/FVC ratio during childhood and adolescence: an intercontinental study. AB - In children, the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV1/FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4-20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV1, leading to falls in FEV1/FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV1/FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV1/FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH. PMID- 20351027 TI - The role of per cent predicted 6-min walk distance in pulmonary arterial hypertension. AB - Absolute 6-min walk distance (6MWD) predicts mortality in pulmonary arterial hypertension (PAH), but varies greatly between normal individuals due to physiological factors such as age, sex, height and weight. The % predicted 6MWD adjusts for these factors and may predict mortality more reliably. The aim of the study was to compare the strength of mortality prediction by absolute and % predicted 6MWD in PAH at baseline and on treatment. % predicted 6MWD was calculated using four different reference equations in 137 PAH patients (idiopathic and connective tissue disease associated) diagnosed between November 2000 and November 2009. Cox proportional hazards and receiver-operating characteristic (ROC) analyses were used to compare the prognostic strength of absolute and % predicted 6MWD. % predicted 6MWD was predictive of all-cause mortality at baseline (hazard ratio 0.74-0.83 per 10% increase; p<0.05) and on treatment (0.67-0.75 per 10% increase; p<0.01), but each respective area under the ROC curve was not different from that of absolute 6MWD for predicting 2-yr mortality at baseline (absolute versus % predicted: 0.74 versus 0.71-0.75) or on treatment (0.77 versus 0.72-0.78). In conclusion, % predicted 6MWD may help clinicians interpret the 6-min walk test, but its prognostic value is not superior to that of absolute 6MWD. PMID- 20351028 TI - Exposure to volatile organic compounds and loss of pulmonary function in the elderly. AB - Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo 2'-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people. PMID- 20351029 TI - Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults. AB - Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947 1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22 56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect. PMID- 20351030 TI - Predicting outcomes and drug resistance with standardised treatment of active tuberculosis. AB - New World Health Organization guidelines recommend initial treatment of active tuberculosis (TB) with a 6-month regimen utilising rifampin throughout. We have modelled expected treatment outcomes, including drug resistance, with this regimen, compared to an 8-month regimen with rifampin for the first 2 months only, followed by standardised retreatment. A deterministic model was used to predict treatment outcomes in hypothetical cohorts of 1,000 new smear-positive cases from seven countries with varying prevalence of initial drug resistance. Model inputs were taken from published systematic reviews. Predicted outcomes included number of deaths, failures and relapses, plus the proportion with drug resistance. Sensitivity analyses examined different risks of acquired drug resistance. Compared to use of the standardised 8-month regimen, for every 1,000 new TB cases treated with the 6-month regimen we predict that 48-86 fewer persons will require retreatment, and 3-12 deaths would be avoided. However, the proportion failing or relapsing after retreatment is predicted to be higher, because with the 6-month regimen 50-94% of failures and 3-56% of relapses will have multidrug-resistant TB. We predict substantial public health benefits from changing from the 8-month to the 6-month regimen. However in almost all settings the current standardised retreatment regimen will no longer be adequate. PMID- 20351031 TI - Plasmacytoid dendritic cells in pulmonary lymphoid follicles of patients with COPD. AB - Plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells with antiviral and tolerogenic capabilities. Viral infections and autoimmunity are proposed to be important mechanisms in the pathogenesis of chronic obstructive pulmonary disease (COPD). The study aimed to quantify blood dendritic cell antigen 2-positive pDCs in lungs of subjects with or without COPD by immunohistochemistry and flow cytometry, combined with the investigation of the influence of cigarette smoke extract (CSE) on the function of pDCs in vitro. pDCs were mainly located in lymphoid follicles, a finding compatible with their expression of lymphoid homing chemokine receptors CXCR3 and CXCR4. pDC accumulated in the lymphoid follicles and in lung digests of patients with mild to moderate COPD, compared with smokers without airflow limitation and patients with COPD Global Initiative for Chronic Obstructive Lung disease (GOLD) stage III IV. Exposing maturing pDC of healthy subjects to CSE in vitro revealed an attenuation of the expression of co-stimulatory molecules and impaired interferon alpha production. Maturing pDC from patients with COPD produced higher levels of tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 compared to pDC from healthy subjects. CSE significantly impairs the antiviral function of pDCs. In COPD, a GOLD stage dependent accumulation of pDC in lymphoid follicles is present, combined with an enhanced production of TNF-alpha and IL-8 by maturing pDCs. PMID- 20351032 TI - Systemic sclerosis and bilateral lung transplantation: a single centre experience. AB - Lung involvement is the leading cause of death in systemic sclerosis (SSc), but lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF). We retrospectively evaluated bilateral LT recipients (LTRs) with SSc or IPF at our centre between January 1, 2003 and December 31, 2007. The primary end-point was all-cause mortality at 1 yr post-LT. Secondary end-points included assessments of acute rejection (AR), pulmonary function, infection and chronic rejection. 14 patients with SSc and 38 patients with IPF underwent LT. Apart from a younger SSc cohort (53.2 versus 58.8 yrs; p = 0.02), the two groups were well matched. 1-yr all-cause mortality was no different between SSc (6.6%) and IPF (13.1%) groups, after adjusting for age (p = 0.62). Rates of (AR) >=2 were significantly increased for the SSc compared with the IPF group (hazard ratio (HR) 2.91; p = 0.007). Other end-points, including chronic rejection, infection and pulmonary function, showed no differences. SSc LTRs experience similar survival 1 yr post-LT when compared to IPF. AR rates may be significantly higher in the SSc group. Longer follow-up is necessary to determine the effects of gastrointestinal dysfunction and AR on late allograft function in SSc LTR. PMID- 20351033 TI - The occupational contribution to severe exacerbation of asthma. AB - The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1-2.6) and high (RR 3.6, 95% CI 2.2-5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02-3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2-5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9-5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role. PMID- 20351034 TI - Fasudil reduces monocrotaline-induced pulmonary arterial hypertension: comparison with bosentan and sildenafil. AB - Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments. Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induced PAH. In addition, the effects of combining bosentan or sildenafil with fasudil were studied. MCT (40 mg.kg body weight(-1)) induced clear PAH in male Wistar rats (n = 9). After 28 days, echocardiography, RV catheterisation and histochemistry showed that cardiac frequency, stroke volume and RV contractility had deteriorated, accompanied by RV dilatation and hypertrophy, and marked pulmonary arterial wall thickening. Mean pulmonary arterial pressure and pulmonary vascular resistance increased significantly compared to healthy rats (n = 9). After 14 days, MCT-treated rats received a 14 day oral treatment with bosentan, sildenafil, fasudil or a combination of fasudil with either bosentan or sildenafil (all n = 9). All treatments preserved cardiac frequency, stroke volume and RV contractility, and reduced pulmonary vascular resistance and RV dilatation. Fasudil lowered RV systolic pressure and mean pulmonary arterial pressure significantly, by reducing pulmonary arterial remodelling, which reduced RV hypertrophy. Combining bosentan or sildenafil with fasudil had no synergistic effect. Fasudil significantly improved PAH, to a greater degree than did bosentan and sildenafil. PMID- 20351035 TI - Epidermal growth factor receptor signalling contributes to house dust mite induced epithelial barrier dysfunction. AB - Impaired airway epithelial barrier function has emerged as a key factor in the pathogenesis of allergic asthma. We aimed to discern the involvement of the epidermal growth factor receptor (EGFR) in allergen-induced epithelial barrier impairment, as we previously observed that house dust mite (HDM) signals through EGFR. We investigated the junctional integrity of human bronchial epithelial cells using electric cell-substrate impedance sensing and immunofluorescent staining. HDM induced a rapid, transient fall in epithelial resistance, concomitant with delocalisation of E-cadherin and zona occludens (ZO)-1, and proteolytic cleavage of the latter. EGFR inhibition by AG1478 reduced the HDM triggered decrease in epithelial resistance and improved restoration of epithelial junctions. Similarly, AG1478 increased epithelial barrier recovery upon electroporation-induced injury, although it delayed the migration phase of the wound healing response. HDM-promoted redistribution of E-cadherin was mediated via EGFR-dependent activation of protease-activated receptor (PAR)-2, while the concomitant ZO-1 degradation was PAR-2/EGFR-independent. Importantly, the fibrogenic cytokine transforming growth factor (TGF)-beta prolonged HDM induced EGFR phosphorylation and inhibited ligand-induced EGFR internalisation/degradation, which resulted in sustained E-cadherin and ZO-1 redistribution. Thus, allergen-induced, PAR-2/EGFR-mediated signalling decreases epithelial resistance and promotes junction disassembly. The TGF-beta-enhanced EGFR signalling may be an important contributor to barrier dysfunction and increased epithelial vulnerability in response to HDM. PMID- 20351036 TI - Long-acting {beta}2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: a study using the GPRD. AB - The objective of this study was to describe risks of death and asthma outcomes with prescription of long-acting beta(2)-agonists (LABA), short-acting beta(2) agonists (SABA) or inhaled corticosteroids (ICS) in general practice. The study population included beta(2)-agonist users aged >=18 yrs, who were in the UK General Practice Research Database (GPRD), which is linked to the national registry of hospitalisations. The study included 507,966 patients with 5.5 million SABA, 4.0 million ICS and 1.3 million LABA prescriptions. Rates of asthma outcome increased with more severe treatment steps. The mortality rate was increased with least and most severe treatment steps. Higher relative rates (RR) of outcomes were found in recent starters and heavy long-term users with LABA, SABA and ICS. The RRs in heavy long-term users were 1.9 for all-cause mortality and 3.0 for asthma death with SABA, 1.4 and 1.6, respectively, with LABA and 1.7 and 2.2, respectively, with ICS. The RR of death was statistically similar over time between LABA and ICS despite changes in exposure. Risks for death and asthma outcomes varied substantially with exposure characteristics. The statistical power for detecting increases in asthma death was low. The results of this study did not indicate that LABA exposure was associated with an increased risk for all cause mortality. PMID- 20351037 TI - Mechanisms of bradykinin-induced contraction in human fetal lung fibroblasts. AB - Bradykinin (BK) induces fibroblast contraction but the structural changes and intracellular mechanisms involved have not been completely explored. We stimulated HFL-1 fibroblasts with BK to assess: 1) fibroblast contractility; 2) the role of alpha-smooth muscle actin (SMA) in contraction by small interfering RNA (siRNA); 3) alpha-SMA protein expression; 4) alpha-SMA and F-actin structure; 5) intracellular calcium concentration ([Ca(2+)](i)); and 6) phosphorylated myosin light-chain (pMLC) and MLC kinase (MLCK) expression. BK triggered concentration- and time-dependent fibroblast gel contraction in conjunction with alpha-SMA over expression, but not in alpha-SMA-siRNA-treated cells. BK also increased alpha-SMA(+) and F-actin(+) cell number and stress fibre polymerisation (detectable at 5-60 min). These BK-induced changes were associated with an increase in [Ca(2+)](i), which peaked within 15 s, and activation of pMLC, which was detectable at 5-60 min. No MLCK content modification was observed. The different manifestations of the BK-induced fibroblast activation were downregulated at different levels (25-100%) by HOE140, a specific BK B2 receptor (B2R) antagonist and by the Ca(2+) chelator, EGTA. Thus, BK-induced fibroblast contraction, associated with differentiation into alpha-SMA(+) myofibroblasts, is mediated through the activation of the B2R and involves the Ca(2+)/calmodulin pMLC-dependent pathway. PMID- 20351038 TI - Phosphoinositide 3-kinase delta inhibitor suppresses interleukin-17 expression in a murine asthma model. AB - Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been recognised as an important cytokine involved in airway inflammation. In the present study, we investigated a role of PI3Kdelta in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma. After ovalbumin inhalation, administration of a selective p110delta inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils and eosinophils, as well as airway hyperresponsiveness, and attenuated the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, -5 and -13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor (NF)-kappaB activity. In addition, a NF kappaB inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL 17 antibody remarkably reduced airway inflammation and hyperresponsiveness. These findings suggest that inhibition of the p110delta signalling pathway suppresses IL-17 expression through regulation of NF-kappaB activity and, thus, has therapeutic potential in asthma. PMID- 20351039 TI - Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis. AB - Altered transforming growth factor (TGF)-beta expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-beta in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-beta1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-beta1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-beta1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF beta1 was overexpressed. Increased cell proliferation, particularly in alpha smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-beta1 overexpression was no longer evident. Therefore, overexpression of TGF-beta1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia. PMID- 20351040 TI - Cognitive factor structure and invariance in people with schizophrenia, their unaffected siblings, and controls. AB - INTRODUCTION: Separable, but positively correlated, factors emerge from analyses of cognitive test data in schizophrenia and control samples (eg, verbal memory and processing speed) and these factors guide data reduction. Additionally, data support a hierarchical model of cognitive performance, in which these correlations reflect the influence of a higher-order factor, referred to as "g." We tested these findings in large, carefully screened samples of people with schizophrenia (n = 496), their unaffected siblings (n = 504), and controls (n = 823). Furthermore, we tested the hypothesis that cognitive performance in schizophrenia is more generalized across domains than among siblings and controls. METHOD: A combination of exploratory and confirmatory factor analyses (EFA and CFA) and multiple groups CFA (MCFA) was used. RESULTS: EFA yielded factors for verbal memory, visual memory, processing speed, working memory span, nback performance, and card sorting. The solution was consistent across groups, in terms of the factor assignments of individual cognitive variables and the magnitude of loadings. Method variance may have contributed to the card sorting, visual memory, and nback factors. CFA indicated that the hierarchical model, incorporating a "g" factor, was a good fit for data from all groups. MCFA suggested that this hierarchical structure was fully invariant for controls and siblings. While the variable/factor loadings for the schizophrenia group also were invariant with comparison groups, factor/"g" loadings were higher in schizophrenia, as were correlations among factor-based composite scores. CONCLUSIONS: Cognitive variables sort into domains consistently in schizophrenia, unaffected siblings, and controls. However, performance in schizophrenia is more generalized and less domain specific. PMID- 20351041 TI - Direct voltage control of endogenous lysophosphatidic acid G-protein-coupled receptors in Xenopus oocytes. AB - Lysophosphatidic acid (LPA) G-protein-coupled receptors (GPCRs) play important roles in a variety of physiological and pathophysiological processes, including cell proliferation, angiogenesis, central nervous system development and carcinogenesis. Whilst many ion channels and transporters are recognized to be controlled by a change in cell membrane potential, little is known about the voltage dependence of other proteins involved in cell signalling. Here, we show that the InsP(3)-mediated Ca(2+) response stimulated by the endogenous LPA GPCR in Xenopus oocytes is potentiated by membrane depolarization. Depolarization was able to repetitively stimulate transient [Ca(2+)](i) increases after the initial agonist-evoked response. In addition, the initial rate and amplitude of the LPA dependent Ca(2+) response were significantly modulated by the steady holding potential over the physiological range, such that the response to LPA was potentiated at depolarized potentials and inhibited at hyperpolarized potentials. Enhancement of LPA receptor-evoked Ca(2+) mobilization by membrane depolarization was observed over a wide range of agonist concentrations. Importantly, the amplitude of the depolarization-evoked intracellular Ca(2+) increase displayed an inverse relationship with agonist concentration such that the greatest effect of voltage was observed at near-threshold levels of agonist. Voltage-dependent Ca(2+) release was not induced by direct elevation of InsP(3) or by activation of heterotrimeric G-proteins in the absence of agonist, indicating that the LPA GPCR itself represents the primary site of action of membrane voltage. This novel modulation of LPA signalling by membrane potential may have important consequences for control of Ca(2+) signals both in excitable and non-excitable tissues. PMID- 20351042 TI - Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. AB - The human sodium channel family includes seven neuronal channels that are essential for the initiation and propagation of action potentials in the CNS and PNS. In view of their critical role in neuronal firing and their strong sequence conservation during evolution, it is not surprising that mutations in the sodium channel genes are responsible for a growing spectrum of channelopathies. Nearly 700 mutations of the SCN1A gene have been identified in patients with Dravet's syndrome (severe myoclonic epilepsy of infancy), making this the most commonly mutated gene in human epilepsy. A small number of mutations have been found in SCN2A, SCN3A and SCN9A, and studies in the mouse suggest that SCN8A may also contribute to seizure disorders. Interactions between genetic variants of SCN2A and KCNQ2 in the mouse and variants of SCN1A and SCN9A in patients provide models of potential genetic modifier effects in the more common human polygenic epilepsies. New methods for generating induced pluripotent stem cells and neurons from patients will facilitate functional analysis of amino acid substitutions in channel proteins. Whole genome sequencing and exome sequencing in patients with epilepsy will soon make it possible to detect multiple variants and their interactions in the genomes of patients with seizure disorders. PMID- 20351043 TI - Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats. AB - Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected. PMID- 20351044 TI - AMPA receptor subunits define properties of state-dependent synaptic plasticity. AB - Many synapses undergo immediate and persistent activity-dependent changes in strength via processes that fall under the umbrella of synaptic plasticity. It is known that this type of synaptic plasticity exhibits an underlying state dependence; that is, as synapses change in strength they move into distinct 'states' that are defined by the mechanism and ability to undergo future plasticity. In this study, we have investigated the molecular mechanisms that underlie state-dependent synaptic plasticity. Using intracellular application of peptides that mimic the C-terminal tail sequences of GluR1 and GluR2 AMPA receptor subtypes, combined with paired recordings of minimal synaptic connections, we have shown that AMPA receptor subtypes present in the membrane at a given time confer some properties of plasticity states. These data show that during synaptic plasticity, AMPA receptor subtypes are differentially stabilized by postsynaptic density proteins in or out of the postsynaptic membrane, and this differential synaptic expression of different AMPA receptor subtypes defines distinct synaptic states. PMID- 20351045 TI - Adrenaline-induced colonic K+ secretion is mediated by KCa1.1 (BK) channels. AB - Colonic epithelial K(+) secretion is a two-step transport process with initial K(+) uptake over the basolateral membrane followed by K(+) channel-dependent exit into the lumen. In this process the large-conductance, Ca(2+)-activated K(Ca)1.1 (BK) channel has been identified as the only apparent secretory K(+) channel in the apical membrane of the murine distal colon. The BK channel is responsible for both resting and Ca(2+)-activated colonic K(+) secretion and is up-regulated by aldosterone. Agonists (e.g. adrenaline) that elevate cAMP are potent activators of distal colonic K(+) secretion. However, the secretory K(+) channel responsible for cAMP-induced K(+) secretion remains to be defined. In this study we used the Ussing chamber to identify adrenaline-induced electrogenic K(+) secretion. We found that the adrenaline-induced electrogenic ion secretion is a compound effect dominated by anion secretion and a smaller electrically opposing K(+) secretion. Using tissue from (i) BK wildtype (BK(+/+)) and knockout (BK(/)) and (ii) cystic fibrosis transmembrane regulator (CFTR) wildtype (CFTR(+/+)) and knockout (CFTR(/)) mice we were able to isolate the adrenaline-induced K(+) secretion. We found that adrenaline-induced K(+) secretion: (1) is absent in colonic epithelia from BK(/) mice, (2) is greatly up-regulated in mice on a high K(+) diet and (3) is present as sustained positive current in colonic epithelia from CFTR(/) mice. We identified two known C-terminal BK alpha-subunit splice variants in colonic enterocytes (STREX and ZERO). Importantly, the ZERO variant known to be activated by cAMP is differentially up-regulated in enterocytes from animals on a high K(+) diet. In summary, these results strongly suggest that the adrenaline-induced distal colonic K(+) secretion is mediated by the BK channel and probably involves aldosterone-induced ZERO splice variant up-regulation. PMID- 20351046 TI - Modulation and function of the autaptic connections of layer V fast spiking interneurons in the rat neocortex. AB - Neocortical fast-spiking (FS) basket cells form dense autaptic connections that provide inhibitory GABAergic feedback after each action potential. It has been suggested that these autaptic connections are used because synaptic communication is sensitive to neuromodulation, unlike the voltage-sensitive potassium channels in FS cells. Here we show that layer V FS interneurons form autaptic connections that are largely perisomatic, and without perturbing intracellular Cl(-) homeostasis, that perisomatic GABAergic currents have a reversal potential of 78 +/- 4 mV. Using variance-mean analysis, we demonstrate that autaptic connections have a mean of 14 release sites (range 4-26) with a quantal amplitude of 101 +/- 16 pA and a probability of release of 0.64 (V(command) = 70 mV, [Ca(2+)](o) = 2 mM, [Mg(2+)](o) = 1 mM). We found that autaptic GABA release is sensitive to GABA(B) and muscarinic acetylcholine receptors, but not a range of other classical neuromodulators. Our results indicate that GABA transporters do not regulate FS interneuron autapses, yet autaptically released GABA does not act at GABA(B) or extrasynaptic GABA(A) receptors. This research confirms that the autaptic connections of FS cells are indeed susceptible to modulation, though only via specific GABAergic and cholinergic mechanisms. PMID- 20351048 TI - Changes in human sensory axonal excitability induced by focal nerve compression. AB - The aim of the present study was to establish the changes in nerve excitability and symptom generation associated with the application of focal nerve compression (FNC). FNC was applied at the wrist by means of a custom-designed electrode in 10 healthy subjects, and was maintained for 24 min. Symptoms of paraesthesiae and signs of numbness were recorded every 30 s. Despite apparently minimal changes in axonal threshold, FNC was associated with prolongation in latency by 14.5 +/- 2.1% (P < 0.001) and reduction in compound sensory action potential (CSAP) amplitude by 34.3 +/- 5.1% (P < 0.001), with two subjects developing conduction block. The reduction in CSAP was associated with abolition of superexcitability, and an increase in refractoriness of 295.2 +/- 55.5% (P < 0.005) and strength duration time constant (SDTC) by 48.1 +/- 10.3% (P < 0.005), all consistent with axonal depolarization. With release of FNC, threshold rapidly increased above pre compression levels (P < 0.01), consistent with the development of axonal hyperpolarization. Associated with these changes in axonal excitability, paraesthesiae and numbness steadily increased throughout FNC and reached a peak at the termination of FNC, followed by a gradual recovery on release of FNC. When compared to previous studies that utilised the effects of more generalised limb ischaemia, the changes in axonal excitability recorded during FNC were qualitatively and quantitatively alike, suggesting that similar biophysical mechanisms contributed to the changes observed with both manoeuvres. PMID- 20351047 TI - Pressure-dependent contribution of Rho kinase-mediated calcium sensitization in serotonin-evoked vasoconstriction of rat cerebral arteries. AB - Our understanding of the cellular signalling mechanisms contributing to agonist induced constriction is almost exclusively based on the study of conduit arteries. Resistance arteries/arterioles have received less attention as standard biochemical approaches lack the necessary sensitivity to permit quantification of phosphoprotein levels in these small vessels. Here, we have employed a novel, highly sensitive Western blotting method to assess: (1) the contribution of Ca(2+) sensitization mediated by phosphorylation of myosin light chain phosphatase targeting subunit 1 (MYPT1) and the 17 kDa PKC-potentiated protein phosphatase 1 inhibitor protein (CPI-17) to serotonin (5-HT)-induced constriction of rat middle cerebral arteries, and (2) whether there is any interplay between pressure-induced myogenic and agonist-induced mechanisms of vasoconstriction. Arterial diameter and levels of MYPT1 (T697 and T855), CPI-17 and 20 kDa myosin light chain subunit (LC(20)) phosphorylation were determined following treatment with 5-HT (1 micromol l(1)) at 10 or 60 mmHg in the absence and presence of H1152 or GF109203X to suppress the activity of Rho-associated kinase (ROK) and protein kinase C (PKC), respectively. Although H1152 and GF109203X suppressed 5-HT induced constriction and reduced phospho-LC(20) content at 10 mmHg, we failed to detect any increase in MYPT1 or CPI-17 phosphorylation. In contrast, an increase in MYPT1-T697 and MYPT1-T855 phosphorylation, but not phospho-CPI-17 content, was apparent at 60 mmHg following exposure to 5-HT, and the phosphorylation of both MYPT1 sites was sensitive to H1152 inhibition of ROK. The involvement of MYPT1 phosphorylation in the response to 5-HT at 60 mmHg was not dependent on force generation per se, as inhibition of cross-bridge cycling with blebbistatin (10 micromol l(1)) did not affect phosphoprotein content. Taken together, the data indicate that Ca(2+) sensitization owing to ROK-mediated phosphorylation of MYPT1 contributes to 5-HT-evoked vasoconstriction only in the presence of pressure induced myogenic activation. These findings provide novel evidence of an interplay between myogenic- and agonist-induced vasoconstriction in cerebral resistance arteries. PMID- 20351049 TI - Initiation of simple and complex spikes in cerebellar Purkinje cells. AB - Cerebellar Purkinje cells produce two distinct forms of action potential output: simple and complex spikes. Simple spikes occur spontaneously or are driven by parallel fibre input, while complex spikes are activated by climbing fibre input. Previous studies indicate that both simple and complex spikes originate in the axon of Purkinje cells, but the precise location where they are initiated is unclear. Here we address where in the axon of cerebellar Purkinje cells simple and complex spikes are generated. Using extracellular recording and voltage sensitive dye imaging in rat and mouse Purkinje cells, we show that both simple and complex spikes are generated in the proximal axon, 15-20 mum from the soma. Once initiated, simple and complex spikes propagate both down the axon and back into the soma. The speed of backpropagation into the soma was significantly faster for complex compared to simple spikes, presumably due to charging of the somatodendritic membrane capacitance during the climbing fibre synaptic conductance. In conclusion, we show using two independent methods that the final integration site of simple and complex spikes is in the proximal axon of cerebellar Purkinje cells, at a location corresponding to the distal end of the axon initial segment. PMID- 20351050 TI - Firing properties and functional connectivity of substantia nigra pars compacta neurones recorded with a multi-electrode array in vitro. AB - Dopamine (DA) neurones of the substantia nigra pars compacta (SNc) are involved in a wide variety of functions, including motor control and reward-based learning. In order to gain new insights into the firing properties of neuronal ensembles in the SNc, we recorded extracellular single units from spontaneously active neurones, using a multi-electrode array (MEA) device in midbrain slices. The majority of neurones (50.21%) had a low firing frequency (1-3 Hz) and a stable pacemaker-like pattern, while others (44.84%) were irregular, but still firing at a low rate. The remaining population (4.95%) comprised neurones with a regular higher firing rate (5-10 Hz). High rate neurones, on the whole, were insensitive to DA (30 mum), while low rate neurones were mostly inhibited by DA, although responding either with a prominent or a weak inhibition. However, we recorded low rate regular neurones that were insensitive to DA, or irregular low rate neurones excited by DA. Interestingly, we found pairs of active neurones (12.10 +/- 3.14%) with a significant proportion of spikes occurring synchronously. Moreover, the crosscorrelation probability in each pair tended to increase in response to DA. In conclusion, MEA recordings in midbrain slices reveal a much more complex picture than previously reported with regard to the firing pattern and DA sensitivity of spontaneously active SNc neurones. Moreover, the study opens new prospectives for the in vitro investigation of functional connectivity in the midbrain dopaminergic system, thus proposing new targets for the pharmacological treatment of DA-dependent neurological disorders. PMID- 20351051 TI - Conserved nucleosome positioning defines replication origins. AB - The origin recognition complex (ORC) specifies replication origin location. The Saccharomyces cerevisiae ORC recognizes the ARS (autonomously replicating sequence) consensus sequence (ACS), but only a subset of potential genomic sites are bound, suggesting other chromosomal features influence ORC binding. Using high-throughput sequencing to map ORC binding and nucleosome positioning, we show that yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin. These findings identify local nucleosomes as an important determinant for origin selection and function. PMID- 20351052 TI - An epigenetic switch governing daughter cell separation in Bacillus subtilis. AB - Growing cells of Bacillus subtilis are a bistable mixture of individual motile cells in which genes for daughter cell separation and motility are ON, and chains of sessile cells in which these genes are OFF. How this ON/OFF switch is controlled has been mysterious. Here we report that a complex of the SinR and SlrR proteins binds to and represses genes involved in cell separation and motility. We also report that SinR and SlrR constitute a double-negative feedback loop in which SinR represses the gene for SlrR (slrR), and, by binding to (titrating) SinR, SlrR prevents SinR from repressing slrR. Thus, SlrR indirectly derepresses its own gene, creating a self-reinforcing loop. Finally, we show that, once activated, the loop remains locked in a high SlrR state in which cell separation and motility genes are OFF for extended periods of time. SinR and SlrR constitute an epigenetic switch for controlling genes involved in cell separation and motility. PMID- 20351053 TI - Nuclear expression of a group II intron is consistent with spliceosomal intron ancestry. AB - Group II introns are self-splicing RNAs found in eubacteria, archaea, and eukaryotic organelles. They are mechanistically similar to the metazoan nuclear spliceosomal introns; therefore, group II introns have been invoked as the progenitors of the eukaryotic pre-mRNA introns. However, the ability of group II introns to function outside of the bacteria-derived organelles is debatable, since they are not found in the nuclear genomes of eukaryotes. Here, we show that the Lactococcus lactis Ll.LtrB group II intron splices accurately and efficiently from different pre-mRNAs in a eukaryote, Saccharomyces cerevisiae. However, a pre mRNA harboring a group II intron is spliced predominantly in the cytoplasm and is subject to nonsense-mediated mRNA decay (NMD), and the mature mRNA from which the group II intron is spliced is poorly translated. In contrast, a pre-mRNA bearing the Tetrahymena group I intron or the yeast spliceosomal ACT1 intron at the same location is not subject to NMD, and the mature mRNA is translated efficiently. Thus, a group II intron can splice from a nuclear transcript, but RNA instability and translation defects would have favored intron loss or evolution into protein dependent spliceosomal introns, consistent with the bacterial group II intron ancestry hypothesis. PMID- 20351055 TI - The glutaredoxin/glutathione system modulates NF-kappaB activity by glutathionylation of p65 in cinnamaldehyde-treated endothelial cells. AB - Reversible protein glutathionylation is an important posttranslational modification that provides protection against oxidation. In endothelial cells (ECs), cinnamaldehyde is an electrophilic compound that can increase the intracellular glutathione (GSH) levels or reactive oxygen species (ROS) production depending on the treatment duration. ECs treated with GSH and H(2)O(2) show increased sulfhydryl modifications of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), which are responsible for NF-kappaB inactivation, and also a block in TNF-alpha-induced p65 nuclear translocation and inter-cellular adhesion molecule-1 (ICAM-1) expression. In our current study, we find that cinnamaldehyde induces p65 glutathionylation and inhibits TNF-alpha-induced p65 nuclear translocation and ICAM-1 expression within 12 h of treatment. Our analyses also reveal that p65 glutathionylation is suppressed by a GSH synthesis inhibitor, buthionine sulfoximine (BSO), and we further observed that the inhibitory effects of p65 nuclear translocation and ICAM-1 expression are also suppressed by BSO. NF-E2-related factor-2 small interfering RNA (siRNA) molecules not only inhibit glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) induction and increases in GSH but also abolish cinnamaldehyde-induced p65 glutathionylation and its inhibitory effects. The gene expression and activity of glutaredoxin-1 (Grx-1), which catalyzes the formation of protein-glutathione mixed disulfides (protein-SSG), were also found to be increased after cinnamaldehyde treatment. A knock down of endogenous Grx-1 by siRNA or pretreatment with an inhibitor of Grx-1 activity, CdCl(2), abolishes p65-SSG formation. In addition, Grx-1 siRNA blocks the inhibition of p65 nuclear translocation and ICAM-1 expression, suggesting that this enzyme is involved in the cinnamaldehyde-mediated NF-kappaB inhibition. Our current results thus indicate that the GSH/Grx-1-dependent glutathionylation of p65 is likely to be responsible for cinnamaldehyde-mediated NF-kappaB inactivation and for the enhanced inhibitory effects of cinnamaldehyde upon TNF-alpha-treated ECs. PMID- 20351056 TI - Risk assessment of N-nitrosodimethylamine formed endogenously after fish-with vegetable meals. AB - The consumption of fish and nitrate-rich vegetables may lead to the formation of the genotoxic carcinogen N-nitrosodimethylamine (NDMA) in the stomach. To assess human cancer risk associated with this formation, a dynamic in vitro gastrointestinal model was used to simulate NDMA formation in the stomach after a fish + vegetable meal. The experimental results were combined with statistical modeling of Dutch food consumption data resulting in predicted exposures to endogenously formed NDMA in the population. The 95th percentile of the long-term exposure distribution was around 4 ng/kg-bw in young children and 0.4 ng/kg-bw in adults. By comparing this exposure with the Benchmark Dose Lower bound (BMDL) 10 for liver cancer in a chronic carcinogenicity study, a chronic margin of exposure (MOE) was calculated of 7000 and 73,000 for young children and adults. Furthermore, the long-term exposure distribution was combined with a dose response analysis of the liver cancer incidence data to obtain a cancer risk distribution for the human population. The 95th percentile of that distribution was 6 x 10(-6) extra risk for 5-year-old children and 8 x 10(-7) for adults. The liver cancer data allowed for the analysis of the relationship between tumor incidence and time to tumor. For an extra risk of 10(-6), the decrease in time to tumor was conservatively estimated at 3.8 min in the rat, equivalent to 0.1 days in humans. We also combined acute exposure estimates with the BMDL10 from an acute carcinogenicity study for NDMA, resulting in an acute MOE of 110,000. We conclude that the combined consumption of fish and nitrate-rich vegetables appears to lead to marginal increases of additional cancer risk. PMID- 20351054 TI - Adaptive evolution of genes duplicated from the Drosophila pseudoobscura neo-X chromosome. AB - Drosophila X chromosomes are disproportionate sources of duplicated genes, and these duplications are usually the result of retrotransposition of X-linked genes to the autosomes. The excess duplication is thought to be driven by natural selection for two reasons: X chromosomes are inactivated during spermatogenesis, and the derived copies of retroposed duplications tend to be testis expressed. Therefore, autosomal derived copies of retroposed genes provide a mechanism for their X-linked paralogs to "escape" X inactivation. Once these duplications have fixed, they may then be selected for male-specific functions. Throughout the evolution of the Drosophila genus, autosomes have fused with X chromosomes along multiple lineages giving rise to neo-X chromosomes. There has also been excess duplication from the two independent neo-X chromosomes that have been examined- one that occurred prior to the common ancestor of the willistoni species group and another that occurred along the lineage leading to Drosophila pseudoobscura. To determine what role natural selection plays in the evolution of genes duplicated from the D. pseudoobscura neo-X chromosome, we analyzed DNA sequence divergence between paralogs, polymorphism within each copy, and the expression profiles of these duplicated genes. We found that the derived copies of all duplicated genes have elevated nonsynonymous polymorphism, suggesting that they are under relaxed selective constraints. The derived copies also tend to have testis- or male-biased expression profiles regardless of their chromosome of origin. Genes duplicated from the neo-X chromosome appear to be under less constraints than those duplicated from other chromosome arms. We also find more evidence for historical adaptive evolution in genes duplicated from the neo-X chromosome, suggesting that they are under a unique selection regime in which elevated nonsynonymous polymorphism provides a large reservoir of functional variants, some of which are fixed by natural selection. PMID- 20351057 TI - Synaptic plasticity and NO-cGMP-PKG signaling coordinately regulate ERK-driven gene expression in the lateral amygdala and in the auditory thalamus following Pavlovian fear conditioning. AB - We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the present series of experiments, we show that N-methyl-D aspartate receptor (NMDAR)-driven synaptic plasticity and NO-cGMP-PKG signaling in the LA regulate the training-induced expression of ERK and the ERK-driven immediate early genes (IEGs) Arc/Arg3.1, c-Fos, and EGR-1 in the LA and the MGm/PIN. Rats receiving intra-LA infusion of the NR2B selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibited significant decreases in ERK activation and in the training-induced expression of all three IEGs in the LA and MGm/PIN while intra-LA infusion of the PKG activator 8-Br-cGMP had the opposite effect. Remarkably, those rats given intra-LA infusion of the membrane impermeable NO scavenger c-PTIO exhibited significant decreases in ERK activation and ERK-driven IEG expression in the MGm/PIN, but not in the LA. Together with our previous experiments, these results suggest that synaptic plasticity and the NO-cGMP-PKG signaling pathway promote fear memory consolidation, in part, by regulating ERK-driven transcription in both the LA and the MGm/PIN. They further suggest that synaptic plasticity in the LA during fear conditioning promotes ERK-driven transcription in MGm/PIN neurons via NO-driven "retrograde signaling." PMID- 20351058 TI - Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. AB - Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(-/-) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b- DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3(-/-) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8alpha+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs. PMID- 20351059 TI - The adaptor molecule CARD9 is essential for tuberculosis control. AB - The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9(-/-) mice succumbed early after aerosol infection, with higher mycobacterial burden, pyogranulomatous pneumonia, accelerated granulocyte recruitment, and higher abundance of proinflammatory cytokines and granulocyte colony-stimulating factor (G-CSF) in serum and lung. Neutralization of G-CSF and neutrophil depletion significantly prolonged survival, indicating that an exacerbated systemic inflammatory disease triggered lethality of Card9(-/-) mice. CARD9 deficiency had no apparent effect on T cell responses, but a marked impact on the hematopoietic compartment. Card9(-/-) granulocytes failed to produce IL-10 after Mycobacterium tuberculosis infection, suggesting that an absent antiinflammatory feedback loop accounted for granulocyte-dominated pathology, uncontrolled bacterial replication, and, ultimately, death of infected Card9(-/-) mice. Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis. PMID- 20351060 TI - Energetics of gating at the apo-acetylcholine receptor transmitter binding site. AB - Acetylcholine receptor channels switch between conformations that have a low versus high affinity for the transmitter and conductance for ions (R<-->R*; gating). The forward isomerization, which begins at the transmitter binding sites and propagates approximately 50 A to the narrow region of the pore, occurs by approximately the same sequence of molecular events with or without agonists present at the binding sites. To pinpoint the forces that govern the R versus R* agonist affinity ratio, we measured single-channel activation parameters for apo receptors having combinations of mutations of 10 transmitter binding site residues in the alpha (Y93, G147, W149, G153, Y190, C192, and Y198), epsilon (W55 and P121), or delta (W57) subunit. Gating energy changes were largest for the tryptophan residues. The alphaW149 energy changes were coupled with those of the other aromatic amino acids. Mutating the aromatic residues to Phe reduces the R/R* equilibrium dissociation constant ratio, with alphaY190 and alphaW149 being the most sensitive positions. Most of the mutations eliminated long-lived spontaneous openings. The results provide a foundation for understanding how ligands trigger protein conformational change. PMID- 20351061 TI - Olfactory response termination involves Ca2+-ATPase in vertebrate olfactory receptor neuron cilia. AB - In vertebrate olfactory receptor neurons (ORNs), odorant-induced activation of the transduction cascade culminates in production of cyclic AMP, which opens cyclic nucleotide-gated channels in the ciliary membrane enabling Ca(2+) influx. The ensuing elevation of the intraciliary Ca(2+) concentration opens Ca(2+) activated Cl(-) channels, which mediate an excitatory Cl(-) efflux from the cilia. In order for the response to terminate, the Cl(-) channel must close, which requires that the intraciliary Ca(2+) concentration return to basal levels. Hitherto, the extrusion of Ca(2+) from the cilia has been thought to depend principally on a Na(+)-Ca(2+) exchanger. In this study, we show using simultaneous suction pipette recording and Ca(2+)-sensitive dye fluorescence measurements that in fire salamander ORNs, withdrawal of external Na(+) from the solution bathing the cilia, which incapacitates Na(+)-Ca(2+)exchange, has only a modest effect on the recovery of the electrical response and the accompanying decay of intraciliary Ca(2+) concentration. In contrast, exposure of the cilia to vanadate or carboxyeosin, a manipulation designed to block Ca(2+)-ATPase, has a substantial effect on response recovery kinetics. Therefore, we conclude that Ca(2+)-ATPase contributes to Ca(2+) extrusion in ORNs, and that Na(+) Ca(2+)exchange makes only a modest contribution to Ca(2+) homeostasis in this species. PMID- 20351062 TI - Carotid body chemosensory responses in mice deficient of TASK channels. AB - Background K(+) channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1( /-) or double TASK1/3(-/-) mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1(-/-) cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either TASK1(-/-) or double TASK1/3(-/-) cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-K(+) channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background K(+) current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O(2)/CO(2) sensing in mouse CB cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of TASK1/3(-/-) glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-K(+) channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the cells a high adaptability to maintain their chemosensory function. PMID- 20351063 TI - A putative role of micro RNA in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes. AB - Cholesterol 7alpha-hydroxylase (CYP7A1) plays a critical role in regulation of bile acid synthesis in the liver. CYP7A1 mRNAs have very short half-lives, and bile acids destabilize CYP7A1 mRNA via the 3'-untranslated region (3'-UTR). However, the underlying mechanism of translational regulation of CYP7A1 mRNA remains unknown. Screening of a human micro RNA (miRNA) microarray has identified five differentially expressed miRNAs in human primary hepatocytes treated with chenodeoxycholic acid, GW4064, or fibroblast growth factor (FGF)19. These compounds also significantly induced the expression of miR-122a, a liver-specific and the predominant miRNA in human hepatocytes. The putative recognition sequences for miR-122a and miR-422a were localized in the 3'-UTR of human CYP7A1 mRNA. The miR-122a and miR-422a mimics inhibited, whereas their inhibitors stimulated CYP7A1 mRNA expression. These miRNAs specifically inhibited the activity of the CYP7A1-3'-UTR reporter plasmids, and mutations of miRNA binding sites in 3'-UTR abrogated miRNA inhibition of reporter activity. These results suggest that miR-122a and miR-422a may destabilize CYP7A1 mRNA to inhibit CYP7A1 expression. However, these miRNAs did not play a role in mediating FGF19 inhibition of CYP7A1 transcription. Under certain conditions, miRNA may reduce CYP7A1 mRNA stability to inhibit bile acid synthesis, and the miR-122a antagomirs may stimulate bile acid synthesis to reduce serum cholesterol and triglycerides. PMID- 20351064 TI - MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro. AB - Smooth muscle cell (SMC) plasticity plays an important role during development and in vascular pathologies such as atherosclerosis and restenosis. It was recently shown that down-regulation of microRNA (miR)-143 and -145, which are coexpressed from a single promoter, regulates the switch from contractile to synthetic phenotype, allowing SMCs to migrate and proliferate. We show in this study that loss of miR-143/145 in vitro and in vivo results in the formation of podosomes, which are actin-rich membrane protrusions involved in the migration of several cell types, including SMCs. We further show that platelet-derived growth factor (PDGF) mediates podosome formation in SMCs through the regulation of miR 143/145 expression via a pathway involving Src and p53. Moreover, we identify key podosome regulators as targets of miR-143 (PDGF receptor alpha and protein kinase C epsilon) and miR-145 (fascin). Thus, dysregulation of the miR-143 and -145 genes is causally involved in the aberrant SMC plasticity encountered during vascular disease, in part through the up-regulation of an autoregulatory loop that promotes podosome formation. PMID- 20351065 TI - BMP-induced REST regulates the establishment and maintenance of astrocytic identity. AB - Once they have differentiated, cells retain their individual character and repress genes that are specifically expressed in other cell lineages, but how alternative fate choice is restricted during and/or after differentiation remains unclear. In the mammalian central nervous system, neurons, astrocytes, and oligodendrocytes are generated throughout life from common tripotent neural progenitor cells (NPCs). Bone morphogenetic proteins (BMPs) are well-known astrocyte-inducing cytokines. We show here that the expression of a transcriptional repressor, RE1 silencer of transcription (REST)/neuron restrictive silencer factor (NRSF), is up-regulated and sustained by BMP signal activation in the course of astrocytic differentiation of NPCs, and restricts neuronal differentiation. We further show that, in differentiated astrocytes, endogenous REST/NRSF associates with various neuronal genes and that disruption of its function resulted in their derepression, thereby explaining how ectopic neuronal gene expression is prevented in cells with astrocytic traits. Collectively, our results suggest that REST/NRSF functions as a molecular regulator of the nonneuronal phenotype in astrocytes. PMID- 20351066 TI - AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. AB - Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate-activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)-only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca(2+) deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. PMID- 20351067 TI - Philip Siekevitz: Bridging biochemistry and cell biology. AB - Philip Siekevitz, an Emeritus Professor at the Rockefeller University who made pioneering contributions to the development of modern cell biology, passed away on December 5th, 2009. He was a creative and enthusiastic scientist, as well as a great experimentalist who throughout his lifetime transmitted the joy of practicing science and the happiness that comes with the acquisition of new knowledge. He was a man of great integrity, with a thoroughly engaging personality and a humility not often found in people of his talent. PMID- 20351070 TI - Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with residual disease following cytotoxic therapy. AB - BACKGROUND: Patients with recurrent ovarian cancer often achieve partial response following chemotherapy, resulting in persistent small volume disease. After completion of treatment, the dilemma of when to initiate subsequent chemotherapy arises. Identification of biomarkers that could be used to predict when subsequent treatment is needed would be of significant benefit. DESIGN: Twenty three patients with advanced ovarian cancer and residual asymptomatic disease following chemotherapy underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at study entry, 4, 8, 12, 18 and 26 weeks or disease progression. A subgroup of patients provided plasma samples within which a panel of angiogenic biomarkers was quantified. RESULTS: By 4 weeks, significant differences in whole tumour volume, enhancing fraction and Ca125 were observed between patients whose disease progressed by 26 weeks and those who remained stable. Significant correlations between plasma soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2 concentrations, and blood volume and tumour endothelial permeability surface area product measured by DCE-MRI were observed. CONCLUSIONS: Imaging markers have a potential role in early prediction of disease progression in patients with residual ovarian cancer and may supplement current measures of progression. The correlation of DCE-MRI and serological biomarkers suggests that tumour angiogenesis affects these markers through common biological means and warrants further investigation. PMID- 20351071 TI - Docetaxel-based combination therapy for castration-resistant prostate cancer. AB - BACKGROUND: Once castration resistance is documented and secondary hormone therapy is ineffective, standard treatment of metastatic prostate cancer is docetaxel, with bisphosphonates and radiopharmaceuticals administered to treat bone symptoms. To improve outcomes, numerous studies have evaluated docetaxel in combination with other agents. Here, results for docetaxel-based combination therapy in castration-resistant prostate cancer (CRPC) are reviewed. MATERIALS AND METHODS: Relevant studies were identified in databases of published literature, clinical trials, and conference abstracts using the search terms docetaxel and prostate, with additional searches carried out for identified agents. RESULTS: Numerous classes of agents have been combined with docetaxel in phase II studies in CRPC, including tyrosine kinase inhibitors, antiangiogenic agents, bone-targeted agents, BCL-2 inhibitors, chemotherapies, immunologic agents, and vitamin D analogs. In several cases, promising rates of prostate specific antigen response, tumor response, and survival have been reported. However, some combinations have caused increased toxicity. Phase III trials with docetaxel plus GVAX or DN-101 were terminated because of lower survival; phase III trials with docetaxel plus bevacizumab, aflibercept, dasatinib, zibotentan, atrasentan, or lenalidomide are ongoing. CONCLUSIONS: Docetaxel-based doublet therapy remains an active investigational strategy in CRPC. Further phase III data are awaited to determine whether survival can be extended compared with docetaxel alone. PMID- 20351069 TI - Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. AB - Epithelial paracellular barrier function, determined primarily by tight junction permeability, is frequently disrupted in disease. In the intestine, barrier loss can be mediated by tumor necrosis factor (alpha) (TNF) signaling and epithelial myosin light chain kinase (MLCK) activation. However, TNF induces only limited alteration of tight junction morphology, and the events that couple structural reorganization to barrier regulation have not been defined. We have used in vivo imaging and transgenic mice expressing fluorescent-tagged occludin and ZO-1 fusion proteins to link occludin endocytosis to TNF-induced tight junction regulation. This endocytosis requires caveolin-1 and is essential for structural and functional tight junction regulation. These data demonstrate that MLCK activation triggers caveolin-1-dependent endocytosis of occludin to effect structural and functional tight junction regulation. PMID- 20351072 TI - Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer. AB - BACKGROUND: Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens. DESIGN: This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04]. RESULTS: The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%-35%) in the large trials. In NSABP B-31/ NCCTG N9831, 5.0%-6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9% 3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%). CONCLUSIONS: Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens. PMID- 20351073 TI - The association between noncancer pain, cognitive impairment, and functional disability: an analysis of the Canadian study of health and aging. AB - BACKGROUND: Noncancer pain and cognitive impairment affect many older adults and each is associated with functional disability, but their combined impact has yet to be rigorously studied. METHODS: This is a cross-sectional analysis of the Canadian Study of Health and Aging. Pain was collapsed from a 5-point to a dichotomous scale (no and very mild vs moderate and greater). Cognitive status was dichotomized from the Modified Mini-Mental State Examination (0-100) to no (>77) or mild-moderate (77-50) impairment. Five Instrumental Activities of Daily Living (IADL) and seven Activities of Daily Living (ADL) were self-rated as "accomplished without any help" (0), "with some help" (1), or "completely unable to do oneself" (2) and then summed to create a composite score of 0-10 and 0-14, respectively. Multivariate linear regression analysis was conducted to determine the associations between self-reported functional status with moderate or greater pain, cognitive impairment, and the interaction of the two. RESULTS: A total of 5,143 (90.2%) participants were eligible, 1,813 (35.6%) reported pain at a moderate intensity or greater and 727 (14.3%) were cognitively impaired. The median IADL and ADL summary scores increased among the pain and cognition categories in the following order: no pain and cognitively intact (0.63 SD 1.24, 0.23 SD 0.80), pain and cognitively intact (1.18 SD 1.69, 0.57 SD 1.27), no pain and cognitively impaired (1.64 SD 2.22, 0.75 SD 1.57), and pain and cognitively impaired (2.27 SD 2.47, 1.35 SD 2.09), respectively. Multivariate linear regression found IADL summary scores were associated with pain, coefficient .17 (95% confidence interval [CI] 0.07-0.26), p < .01; cognitive impairment, coefficient .67 (95% CI 0.51-0.83), p < .01; and an interaction effect of pain with cognitive impairment, coefficient .24 (95% CI 0.01-0.49), p = .05. ADL summary scores were associated with pain coefficient .10 (95% CI 0.04-0.17), p < .01 and cognitive impairment, coefficient .29 (95% CI 0.19-0.39), p < .01, but had a nonsignificant interaction term, coefficient .12 (95% CI -0.03 to 0.29), p = .12. CONCLUSIONS: Noncancer pain and cognitive impairment are independently associated with IADL and ADL impairment and IADL impairment is even greater when both conditions are present. PMID- 20351074 TI - Caregiving, metabolic syndrome indicators, and 1-year decline in walking speed: results of Caregiver-SOF. AB - BACKGROUND: Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers. METHODS: The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term ((3)4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index (3)30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews. RESULTS: Walking speed declined for the total sample (adjusted mean = -0.005 m/second, +/-0.16) over an average of 1.04 years (+/ 0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3-4 metabolic indicators (-0.10 m/second and -0.155 m/second, respectively). CONCLUSIONS: Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline. PMID- 20351076 TI - My year without drug reps. PMID- 20351077 TI - Patient safety. Wise before the event. PMID- 20351075 TI - Longevity and age-related pathology of mice deficient in pregnancy-associated plasma protein-A. AB - The pregnancy-associated plasma protein-A knockout (PAPP-A KO) mouse is a model of reduced local insulin-like growth factor (IGF)-I activity with normal circulating IGF-I levels. In this study, PAPP-A KO mice had significantly increased mean (27%), median (27%), and maximum (35%) life span compared with wild-type (WT) littermates. End-of-life pathology indicated that the incidence of neoplastic disease was not significantly different in the two groups of mice; however, it occurred in older aged PAPP-A KO compared with WT mice. Furthermore, PAPP-A KO mice were less likely to show degenerative changes of age. Scheduled pathologies at 78, 104, and 130 weeks of age indicated that WT mice, in general, had more degenerative changes and tumors earlier than PAPP-A KO mice. This was particularly true for abnormalities in heart, testes, brain, kidney, spleen, and thymus. In summary, the major contributors to the extended life span of PAPP-A KO mice are delayed occurrence of fatal neoplasias and decreased incidence of age related degenerative changes. PMID- 20351078 TI - Challenges for WHO code on international recruitment. PMID- 20351080 TI - Spanish transplant model would save 20,000 lives a year in EU. PMID- 20351081 TI - An author spurned. PMID- 20351085 TI - Human papillomavirus vaccine project stirs controversy in India. PMID- 20351091 TI - EPS8 upregulates FOXM1 expression, enhancing cell growth and motility. AB - Previous studies from our laboratory have indicated that overexpression of the epidermal growth factor receptor pathway substrate 8 (EPS8) enhances cell proliferation, migration and tumorigenicity in vivo, although the mechanisms involved remain unexplored. A microarray screen to search for potential mediators of EPS8 identified upregulation of multiple cell cycle-related targets such as the transcription factor FOXM1 and several of its reported downstream mediators, including cdc20, cyclin B1, cyclin A, aurora-B kinase and cdc25C in cells with elevated EPS8, as well as matrix metalloproteinase-9, which we reported previously to be upregulated by EPS8-dependent mechanisms. Cells engineered to overexpress FOXM1 showed increased proliferation, similar to EPS8-overexpressing cells. Conversely, targeted knockdown of FOXM1 in EPS8-overexpressing cells reduced proliferation. Cotransfection of EPS8 with a FOXM1-luciferase reporter plasmid into 293-T- or SVpgC2a-immortalized buccal keratinocytes demonstrated that EPS8 enhances FOXM1 promoter activity, whereas chromatin immunoprecipitation assays revealed elevated levels of acetylated histone H3 associated with the FOXM1 promoter in cells expressing high levels of EPS8. Treatment of EPS8 overexpressing cells with inhibitors of phosphoinositide 3-OH kinase or AKT reduced expression of FOXM1 and aurora-B kinase, a transcriptional target of FOXM1. Overexpression of EPS8 induced expression of the chemokine ligands CXCL5 and CXCL12 in a FOXM1-dependent manner, which was blocked by LY294002 or a dominant-negative form of AKT. Additionally, overexpression of FOXM1 enhanced cell migration, whereas targeted knockdown of CXCL5 or inhibition of AKT reduced migration of EPS8-expressing cells. These data suggest that EPS8 enhances cell proliferation and migration in part by deregulating FOXM1 activity and inducing CXC-chemokine expression, mediated by PI3K- and AKT-dependent mechanisms. PMID- 20351092 TI - Homologous recombination in cancer development, treatment and development of drug resistance. AB - Although DNA double-strand breaks (DSBs) are substrates for homologous recombination (HR) repair, it is becoming apparent that DNA lesions produced at replication forks, for instance by many anticancer drugs, are more significant substrates for HR repair. Cells defective in HR are hypersensitive to a wide variety of anticancer drugs, including those that do not produce DSBs. Several cancers have mutations in or epigenetically silenced HR genes, which explain the genetic instability that drives cancer development. There are an increasing number of reports suggesting that mutation or epigenetic silencing of HR genes explains the sensitivity of cancers to current chemotherapy treatments. Furthermore, there are also many examples of re-expression of HR genes in tumours to explain drug resistance. Emerging data suggest that there are several different subpathways of HR, which can compensate for each other. Unravelling the overlapping pathways in HR showed that BRCA1- and BRCA2-defective cells rely on the PARP protein for survival. This synthetic lethal interaction is now being exploited for selective treatment of BRCA1- and BRCA2-defective cancers with PARP inhibitors. Here, I discuss the diversity of HR and how it impacts on cancer with a particular focus on how HR can be exploited in future anticancer strategies. PMID- 20351093 TI - MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3' untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using gamma-secretase inhibitor (N-[N-(3,5 difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme. PMID- 20351094 TI - Sp1 regulates chromatin looping between an intronic enhancer and distal promoter of the human heme oxygenase-1 gene in renal cells. AB - HO-1 (heme oxygenase-1) is an inducible microsomal enzyme that catalyzes the degradation of pro-oxidant heme. The goal of this study was to characterize a minimal enhancer region within the human HO-1 gene and delineate its role in modulating HO-1 expression by participation with its promoter elements in renal epithelial cells. Deletion analysis and site-directed mutagenesis identified a 220-bp minimal enhancer in intron 1 of the HO-1 gene, which regulates hemin mediated HO-1 gene expression. Small interfering RNA, decoy oligonucleotides, site-directed mutagenesis, and chromatin immunoprecipitation assays confirmed the functional interaction of Sp1 with a consensus binding sequence within the 220-bp region. Mutations of regulatory elements within the -4.5 kb promoter region (a cyclic AMP response and a downstream NF-E2/AP-1 element, both located at -4.0 kb, and/or an E-box sequence located at -44 bp) resulted in the loss of enhancer activity. A chromosome conformation capture assay performed in human renal epithelial (HK-2) cells demonstrated hemin-inducible chromatin looping between the intronic enhancer and the -4.0 kb promoter region in a time-dependent manner. Restriction digestion with ApaLI (which cleaves the 220-bp enhancer) led to a loss of stimulus-dependent chromatin looping. Sp1 small interfering RNA and mithramycin A, a Sp1 binding site inhibitor, resulted in loss of the loop formation between the intronic enhancer and the distal HO-1 promoter by the chromosome conformation capture assay. These results provide novel insight into the complex molecular interactions that underlie human HO-1 regulation in renal epithelial cells. PMID- 20351095 TI - Role of direct interactions between the histone H4 Tail and the H2A core in long range nucleosome contacts. AB - In eukaryotic nuclei the majority of genomic DNA is believed to exist in higher order chromatin structures. Nonetheless, the nature of direct, long range nucleosome interactions that contribute to these structures is poorly understood. To determine whether these interactions are directly mediated by contacts between the histone H4 amino-terminal tail and the acidic patch of the H2A/H2B interface, as previously demonstrated for short range nucleosomal interactions, we have characterized the extent and effect of disulfide cross-linking between residues in histones contained in different strands of nucleosomal arrays. We show that in 208-12 5 S rDNA and 601-177-12 nucleosomal array systems, direct interactions between histones H4-V21C and H2A-E64C can be captured. This interaction depends on the extent of initial cross-strand association but does not require these specific residues, because interactions with residues flanking H4-V21C can also be captured. Additionally, we find that trapping H2A-H4 intra-array interactions antagonizes the ability of these arrays to undergo intermolecular self association. PMID- 20351096 TI - Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine. AB - The actin motor myosin VI regulates endocytosis of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestine, but the endocytic adaptor linking CFTR to myosin VI is unknown. Dab2 (Disabled 2) is the binding partner for myosin VI, clathrin, and alpha-AP-2 and directs endocytosis of low density lipoprotein receptor family members by recognizing a phosphotyrosine-binding domain. However, CFTR does not possess a phosphotyrosine-binding domain. We examined whether alpha AP-2 and/or Dab2 were binding partners for CFTR and the role of myosin VI in localizing endocytic adaptors in the intestine. CFTR co-localized with alpha-AP 2, Dab2, and myosin VI and was identified in a complex with all three endocytic proteins in the intestine. Apical CFTR was increased in the intestines of Dab-2 KO mice, suggesting its involvement in regulating surface CFTR. Glutathione S transferase pulldown assays revealed binding of CFTR to alpha-AP-2 (but not Dab2) in the intestine, whereas Dab-2 interacted with alpha-AP-2. siRNA silencing of alpha-AP-2 in cells significantly reduced CFTR endocytosis, further supporting alpha-AP-2 as the direct binding partner for CFTR. alpha-AP-2 and Dab2 localized to the terminal web regions of enterocytes, but Dab2 accumulated in this location in Snell's Waltzer myosin VI((sv/sv)) intestine. Ultrastructural examination revealed that the accumulation of Dab2 correlated with prominent involution and the loss of normal positioning of the intermicrovillar membranes that resulted in expansion of the terminal web region in myosin VI((sv/sv)) enterocytes. The findings support alpha-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes. PMID- 20351097 TI - Omp85 from the thermophilic cyanobacterium Thermosynechococcus elongatus differs from proteobacterial Omp85 in structure and domain composition. AB - Omp85 proteins are essential proteins located in the bacterial outer membrane. They are involved in outer membrane biogenesis and assist outer membrane protein insertion and folding by an unknown mechanism. Homologous proteins exist in eukaryotes, where they mediate outer membrane assembly in organelles of endosymbiotic origin, the mitochondria and chloroplasts. We set out to explore the homologous relationship between cyanobacteria and chloroplasts, studying the Omp85 protein from the thermophilic cyanobacterium Thermosynechococcus elongatus. Using state-of-the art sequence analysis and clustering methods, we show how this protein is more closely related to its chloroplast homologue Toc75 than to proteobacterial Omp85, a finding supported by single channel conductance measurements. We have solved the structure of the periplasmic part of the protein to 1.97 A resolution, and we demonstrate that in contrast to Omp85 from Escherichia coli the protein has only three, not five, polypeptide transport associated (POTRA) domains, which recognize substrates and generally interact with other proteins in bigger complexes. We model how these POTRA domains are attached to the outer membrane, based on the relationship of Omp85 to two-partner secretion system proteins, which we show and analyze. Finally, we discuss how Omp85 proteins with different numbers of POTRA domains evolved, and evolve to this day, to accomplish an increasing number of interactions with substrates and helper proteins. PMID- 20351098 TI - Cystic fibrosis transmembrane conductance regulator interacts with multiple immunoglobulin domains of filamin A. AB - Mutations of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) that impair its apical localization and function cause cystic fibrosis. A previous report has shown that filamin A (FLNa), an actin-cross linking and -scaffolding protein, interacts directly with the cytoplasmic N terminus of CFTR and that this interaction is necessary for stability and confinement of the channel to apical membranes. Here, we report that the CFTR N terminus has sequence similarity to known FLNa-binding partner-binding sites. FLNa has 24 Ig (IgFLNa) repeats, and a CFTR peptide pulled down repeats 9, 12, 17, 19, 21, and 23, which share sequence similarity yet differ from the other FLNa Ig domains. Using known structures of IgFLNa.partner complexes as templates, we generated in silico models of IgFLNa.CFTR peptide complexes. Point and deletion mutants of IgFLNa and CFTR informed by the models, including disease causing mutations L15P and W19C, disrupted the binding interaction. The model predicted that a P5L CFTR mutation should not affect binding, but a synthetic P5L mutant peptide had reduced solubility, suggesting a different disease-causing mechanism. Taken together with the fact that FLNa dimers are elongated ( approximately 160 nm) strands, whereas CFTR is compact (6 approximately 8 nm), we propose that a single FLNa molecule can scaffold multiple CFTR partners. Unlike previously defined dimeric FLNa.partner complexes, the FLNa-monomeric CFTR interaction is relatively weak, presumptively facilitating dynamic clustering of CFTR at cell membranes. Finally, we show that deletion of all CFTR interacting domains from FLNa suppresses the surface expression of CFTR on baby hamster kidney cells. PMID- 20351099 TI - Altered linkage of hydroxyacyl chains in lipid A of Campylobacter jejuni reduces TLR4 activation and antimicrobial resistance. AB - Modification of the lipid A moiety of bacterial lipopolysaccharide influences cell wall properties, endotoxic activity, and bacterial resistance to antimicrobial peptides. Known modifications are variation in the number or length of acyl chains and/or attached phosphoryl groups. Here we identified two genes (gnnA and gnnB) in the major foodborne pathogen Campylobacter jejuni that enable the synthesis of a GlcN3N precursor UDP 2-acetamido-3-amino-2,3-dideoxy-alpha-D glucopyranose (UDP-GlcNAc3N) in the lipid A backbone. Mass spectrometry of purified lipooligosaccharide verified that the gene products facilitate the formation of a 2,3-diamino-2,3-dideoxy-D-glucose (GlcN3N) disaccharide lipid A backbone when compared with the beta-1'-6-linked D-glucosamine (GlcN) disaccharide observed in Escherichia coli lipid A. Functional assays showed that inactivation of the gnnA or gnnB gene enhanced the TLR4-MD2-mediated NF-kappaB activation. The mutants also displayed increased susceptibility to killing by the antimicrobial peptides polymyxin B, colistin and the chicken cathelicidin-1. The gnnA and gnnB genes are organized in one operon with hemH, encoding a ferrochelatase catalyzing the last step in heme biosynthesis. These results indicate that lipid A modification resulting in amide-linked acyl chains in the lipid A is an effective mechanism to evade activation of the innate host defense and killing by antimicrobial peptides. PMID- 20351100 TI - A low affinity ground state conformation for the Dynein microtubule binding domain. AB - Dynein interacts with microtubules through a dedicated binding domain that is dynamically controlled to achieve high or low affinity, depending on the state of nucleotide bound in a distant catalytic pocket. The active sites for microtubule binding and ATP hydrolysis communicate via conformational changes transduced through a approximately 10-nm length antiparallel coiled-coil stalk, which connects the binding domain to the roughly 300-kDa motor core. Recently, an x-ray structure of the murine cytoplasmic dynein microtubule binding domain (MTBD) in a weak affinity conformation was published, containing a covalently constrained beta(+) registry for the coiled-coil stalk segment (Carter, A. P., Garbarino, J. E., Wilson-Kubalek, E. M., Shipley, W. E., Cho, C., Milligan, R. A., Vale, R. D., and Gibbons, I. R. (2008) Science 322, 1691-1695). We here present an NMR analysis of the isolated MTBD from Dictyostelium discoideum that demonstrates the coiled-coil beta(+) registry corresponds to the low energy conformation for this functional region of dynein. Addition of sequence encoding roughly half of the coiled-coil stalk proximal to the binding tip results in a decreased affinity of the MTBD for microtubules. In contrast, addition of the complete coiled-coil sequence drives the MTBD to the conformationally unstable, high affinity binding state. These results suggest a thermodynamic coupling between conformational free energy differences in the alpha and beta(+) registries of the coiled-coil stalk that acts as a switch between high and low affinity conformations of the MTBD. A balancing of opposing conformations in the stalk and MTBD enables potentially modest long-range interactions arising from ATP binding in the motor core to induce a relaxation of the MTBD into the stable low affinity state. PMID- 20351101 TI - Biochemical basis of the interaction between cystic fibrosis transmembrane conductance regulator and immunoglobulin-like repeats of filamin. AB - Mutations in the chloride channel cystic fibrosis transmembrane regulator (CFTR) cause cystic fibrosis, a genetic disorder characterized by defects in CFTR biosynthesis, localization to the cell surface, or activation by regulatory factors. It was discovered recently that surface localization of CFTR is stabilized by an interaction between the CFTR N terminus and the multidomain cytoskeletal protein filamin. The details of the CFTR-filamin interaction, however, are unclear. Using x-ray crystallography, we show how the CFTR N terminus binds to immunoglobulin-like repeat 21 of filamin A (FlnA-Ig21). CFTR binds to beta-strands C and D of FlnA-Ig21 using backbone-backbone hydrogen bonds, a linchpin serine residue, and hydrophobic side-chain packing. We use NMR to determine that the CFTR N terminus also binds to several other immunoglobulin like repeats from filamin A in vitro. Our structural data explain why the cystic fibrosis-causing S13F mutation disrupts CFTR-filamin interaction. We show that FlnA-Ig repeats transfected into cultured Calu-3 cells disrupt CFTR-filamin interaction and reduce surface levels of CFTR. Our findings suggest that filamin A stabilizes surface CFTR by anchoring it to the actin cytoskeleton through interactions with multiple filamin Ig repeats. Such an interaction mode may allow filamins to cluster multiple CFTR molecules and to promote colocalization of CFTR and other filamin-binding proteins in the apical plasma membrane of epithelial cells. PMID- 20351102 TI - Oral administration of a GSK3 inhibitor increases brain insulin-like growth factor I levels. AB - Reduced brain input of serum insulin-like growth factor I (IGF-I), a potent neurotrophic peptide, may be associated with neurodegenerative processes. Thus, analysis of the mechanisms involved in passage of blood-borne IGF-I into the brain may shed light onto pathological mechanisms in neurodegeneration and provide new drug targets. A site of entrance of serum IGF-I into the brain is the choroid plexus. The transport mechanism for IGF-I in this specialized epithelium involves the IGF-I receptor and the membrane multicargo transporter megalin/LRP2. We have now analyzed this process in greater detail and found that the IGF-I receptor interacts with the transmembrane region of megalin, whereas the perimembrane domain of megalin is required for IGF-I internalization. Furthermore, a GSK3 site within the Src homology 3 domain of the C-terminal region of megalin is a key regulator of IGF-I transport. Thus, inhibition of GSK3 markedly increased internalization of IGF-I, whereas mutation of this GSK3 site abrogated this increase. Notably, oral administration of a GSK3 inhibitor to adult wild-type mice or to amyloid precursor protein/presenilin 1 mice modeling Alzheimer amyloidosis significantly increased brain IGF-I content. These results indicate that pharmacological modulation of IGF-I transport by megalin may be used to increase brain availability of serum IGF-I. Interestingly, GSK3 inhibitors such as those under development to treat Alzheimer disease may show therapeutic efficacy in part by increasing brain IGF-I levels, an effect already reported for other neuroprotective compounds. PMID- 20351104 TI - The vertebrate lysozyme inhibitor Ivy functions to inhibit the activity of lytic transglycosylase. AB - The proteinaceous inhibitor of vertebrate lysozymes (Ivy) is produced by a collection of Gram-negative bacteria as a stress response to damage to their essential cell wall component peptidoglycan. A paralog of Ivy, Ivyp2 is produced exclusively by a number of pseudomonads, including Pseudomonas aeruginosa, but this protein does not inhibit the lysozymes, and its function was unknown. In this study, we demonstrate that the production of Ivy (homologs of both Ivyp1 and Ivyp2) correlates with bacteria that do not O-acetylate their peptidoglycan, a modification that controls the activity of the lytic transglycosylases. Furthermore, we show that both Ivy proteins are potent inhibitors of the lytic transglycoslyases, enzymes involved in the biosynthesis and maintenance of peptidoglycan. These data suggest that the true physiological function of the Ivy proteins is to control the autolytic activity of lytic transglycosylases within the periplasm of Gram-negative bacteria that do not produce O-acetylated peptidoglycan and that the inhibition of exogenous lysozyme by Ivy is simply a fortuitous coincidence. PMID- 20351103 TI - Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation. AB - Inactivation of the mainly endosomal 2Cl(-)/H(+)-exchanger ClC-5 severely impairs endocytosis in renal proximal tubules and underlies the human kidney stone disorder Dent's disease. In heterologous expression systems, interaction of the E3 ubiquitin ligases WWP2 and Nedd4-2 with a "PY-motif" in the cytoplasmic C terminus of ClC-5 stimulates its internalization from the plasma membrane and may influence receptor-mediated endocytosis. We asked whether this interaction is relevant in vivo and generated mice in which the PY-motif was destroyed by a point mutation. Unlike ClC-5 knock-out mice, these knock-in mice displayed neither low molecular weight proteinuria nor hyperphosphaturia, and both receptor mediated and fluid-phase endocytosis were normal. The abundances and localizations of the endocytic receptor megalin and of the Na(+)-coupled phosphate transporter NaPi-2a (Npt2) were not changed, either. To explore whether the discrepancy in results from heterologous expression studies might be due to heteromerization of ClC-5 with ClC-3 or ClC-4 in vivo, we studied knock-in mice additionally deleted for those related transporters. Disruption of neither ClC-3 nor ClC-4 led to proteinuria or impaired proximal tubular endocytosis by itself, nor in combination with the PY-mutant of ClC-5. Endocytosis of cells lacking ClC 5 was not impaired further when ClC-3 or ClC-4 was additionally deleted. We conclude that ClC-5 is unique among CLC proteins in being crucial for proximal tubular endocytosis and that PY-motif-dependent ubiquitylation of ClC-5 is dispensable for this role. PMID- 20351105 TI - Placenta growth factor (PlGF), a novel inducer of plasminogen activator inhibitor 1 (PAI-1) in sickle cell disease (SCD). AB - Sickle cell disease (SCD) is characterized by a prothrombotic state. Plasminogen activator inhibitor-1 (PAI-1) is known to modulate fibrinolysis, lung injury/fibrosis, and angiogenesis. However, its role in SCD is less understood, and the molecular mechanisms underlying increased PAI-1 are unknown. Herein, we show a novel link between PAI-1 and sickle erythropoiesis. Plasma PAI-1 levels were high in SCD patients at steady state and in two humanized sickle mouse models, with increased PAI-1 immunolabeling in sickle mouse lung, bronchial epithelial cells, alveolar macrophages, and pulmonary microvascular endothelial cells. Placenta growth factor (PlGF), released at high levels by sickle erythroblasts, induced PAI-1 expression in primary human pulmonary microvascular endothelial cells and monocytes through activation of c-Jun N-terminal kinase (JNK), NADPH oxidase, and hypoxia-inducible factor-1alpha (HIF-1alpha). Analysis of the human PAI-1 promoter revealed this induction was mediated by hypoxia response element (HRE)-1, HRE-2, and distal activator protein (AP-1) sites. We also identify the involvement of c-Jun, c-Jun/c-Fos, and JunD, but not JunB, in binding with AP-1 sites of the PAI-1 promoter upon PlGF induction. Consistent with these findings, levels of PAI-1 were low in PlGF knock-out mice and sickle PlGF knock-out mice; overexpression of PlGF in normal mice increased circulating PAI-1. In conclusion, we identify a novel mechanism of PAI-1 elevation in SCD. PMID- 20351106 TI - Separate gating mechanisms mediate the regulation of K2P potassium channel TASK-2 by intra- and extracellular pH. AB - TASK-2 (KCNK5 or K(2P)5.1) is a background K(+) channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pH(o)) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pH(i)) is independent from that under the command of pH(o). It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pH(o) had normal pH(i)-dependent gating. Increasing extracellular K(+) concentration acid shifts pH(o) activity curve of TASK-2 yet did not affect pH(i) gating of TASK-2. pH(o) modulation of TASK-2 is voltage-dependent, whereas pH(i) gating was not altered by membrane potential. These results suggest that pH(o), which controls a selectivity filter external gate, and pH(i) act at different gating processes to open and close TASK-2 channels. We speculate that pH(i) regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys(245)) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pH(i). We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pH(i) dependence curve of TASK-2 as expected from its lower pK(a). We conclude that intracellular pH, together with pH(o), is a critical determinant of TASK-2 activity and therefore of its physiological function. PMID- 20351107 TI - Differential gene expression downstream of Toll-like receptors (TLRs): role of c Src and activating transcription factor 3 (ATF3). AB - Interferon regulatory factors (IRFs) are crucial for transcription during innate immune responses. We have previously shown that the tyrosine kinase c-Src enhances IRF-3-dependent transcription in response to viral double-stranded RNA. In this study, we show that c-Src has distinct roles in Toll-like receptor (TLR) mediated activation of IRF-5 and IRF-3. Surprisingly, c-Src inhibition markedly enhanced IRF-5 activation after treatment with unmethylated CpG, while suppressing IRF-3 activation. Also, CpG-elicited interleukin-6 mRNA production was increased, whereas IP10 mRNA synthesis was reduced in cells deficient in c Src. Interestingly, c-Src regulated TLR-stimulated induction of activating transcription factor 3 (ATF3), a transcriptional repressor. Depletion of ATF3 by small interfering RNA markedly enhanced interleukin-6 production after CpG treatment, whereas IP10 production was reduced. These results demonstrate functional specificity for c-Src in TLR-stimulated responses and suggest that c Src modulation and ATF3 activity may contribute to differential regulation of IRF 3- versus IRF-5-mediated gene expression. PMID- 20351108 TI - Mechanism of intraparticle synthesis of the rotavirus double-stranded RNA genome. AB - Rotaviruses perform the remarkable tasks of transcribing and replicating 11 distinct double-stranded RNA genome segments within the confines of a subviral particle. Multiple viral polymerases are tethered to the interior of a particle, each dedicated to a solitary genome segment but acting in synchrony to synthesize RNA. Although the rotavirus polymerase specifically recognizes RNA templates in the absence of other proteins, its enzymatic activity is contingent upon interaction with the viral capsid. This intraparticle strategy of RNA synthesis helps orchestrate the concerted packaging and replication of the viral genome. Here, we review our current understanding of rotavirus RNA synthetic mechanisms. PMID- 20351109 TI - Biochemical conservation and evolution of germacrene A oxidase in asteraceae. AB - Sesquiterpene lactones are characteristic natural products in Asteraceae, which constitutes approximately 8% of all plant species. Despite their physiological and pharmaceutical importance, the biochemistry and evolution of sesquiterpene lactones remain unexplored. Here we show that germacrene A oxidase (GAO), evolutionarily conserved in all major subfamilies of Asteraceae, catalyzes three consecutive oxidations of germacrene A to yield germacrene A acid. Furthermore, it is also capable of oxidizing non-natural substrate amorphadiene. Co-expression of lettuce GAO with germacrene synthase in engineered yeast synthesized aberrant products, costic acids and ilicic acid, in an acidic condition. However, cultivation in a neutral condition allowed the de novo synthesis of a single novel compound that was identified as germacrene A acid by gas and liquid chromatography and NMR analyses. To trace the evolutionary lineage of GAO in Asteraceae, homologous genes were further isolated from the representative species of three major subfamilies of Asteraceae (sunflower, chicory, and costus from Asteroideae, Cichorioideae, and Carduoideae, respectively) and also from the phylogenetically basal species, Barnadesia spinosa, from Barnadesioideae. The recombinant GAOs from these genes clearly showed germacrene A oxidase activities, suggesting that GAO activity is widely conserved in Asteraceae including the basal lineage. All GAOs could catalyze the three-step oxidation of non-natural substrate amorphadiene to artemisinic acid, whereas amorphadiene oxidase diverged from GAO displayed negligible activity for germacrene A oxidation. The observed amorphadiene oxidase activity in GAOs suggests that the catalytic plasticity is embedded in ancestral GAO enzymes that may contribute to the chemical and catalytic diversity in nature. PMID- 20351110 TI - A new group of aromatic prenyltransferases in fungi, catalyzing a 2,7 dihydroxynaphthalene 3-dimethylallyl-transferase reaction. AB - Five fungal genomes from the Ascomycota (sac fungi) were found to contain a gene with sequence similarity to a recently discovered small group of bacterial prenyltransferases that catalyze the C-prenylation of aromatic substrates in secondary metabolism. The genes from Aspergillus terreus NIH2624, Botryotinia fuckeliana B05.10 and Sclerotinia sclerotiorum 1980 were expressed in Escherichia coli, and the resulting His(8)-tagged proteins were purified and investigated biochemically. Their substrate specificity was found to be different from that of any other prenyltransferase investigated previously. Using 2,7 dihydroxynaphthalene (2,7-DHN) and dimethylallyl diphosphate as substrates, they catalyzed a regiospecific Friedel-Crafts alkylation of 2,7-DHN at position 3. Using the enzyme of A. terreus, the K(m) values for 2,7-DHN and dimethylallyl diphosphate were determined as 324 +/- 25 microM and 325 +/- 35 microM, respectively, and k(cat) as 0.026 +/- 0.001 s(-1). A significantly lower level of prenylation activity was found using dihydrophenazine-1-carboxylic acid as aromatic substrate, and only traces of products were detected with aspulvinone E, flaviolin, or 4-hydroxybenzoic acid. No product was formed with l-tryptophan, l tyrosine, or 4-hydroxyphenylpyruvate. The genes for these fungal prenyltransferases are not located within recognizable secondary metabolic gene clusters. Their physiological function is yet unknown. PMID- 20351111 TI - Characterization of the semiquinone radical stabilized by the cytochrome aa3-600 menaquinol oxidase of Bacillus subtilis. AB - Cytochrome aa(3)-600 is one of the principle respiratory oxidases from Bacillus subtilis and is a member of the heme-copper superfamily of oxygen reductases. This enzyme catalyzes the two-electron oxidation of menaquinol and the four electron reduction of O(2) to 2H(2)O. Cytochrome aa(3)-600 is of interest because it is a very close homologue of the cytochrome bo(3) ubiquinol oxidase from Escherichia coli, except that it uses menaquinol instead of ubiquinol as a substrate. One question of interest is how the proteins differ in response to the differences in structure and electrochemical properties between ubiquinol and menaquinol. Cytochrome bo(3) has a high affinity binding site for ubiquinol that stabilizes a ubi-semiquinone. This has permitted the use of pulsed EPR techniques to investigate the protein interaction with the ubiquinone. The current work initiates studies to characterize the equivalent site in cytochrome aa(3)-600. Cytochrome aa(3)-600 has been cloned and expressed in a His-tagged form in B. subtilis. After isolation of the enzyme in dodecylmaltoside, it is shown that the pure enzyme contains 1 eq of menaquinone-7 and that the enzyme stabilizes a mena semiquinone. Pulsed EPR studies have shown that there are both similarities as well as significant differences in the interactions of the mena-semiquinone with cytochrome aa(3)-600 in comparison with the ubi-semiquinone in cytochrome bo(3). Our data indicate weaker hydrogen bonds of the menaquinone in cytochrome aa(3) 600 in comparison with ubiquinone in cytochrome bo(3). In addition, the electronic structure of the semiquinone cyt aa(3)-600 is more shifted toward the anionic form from the neutral state in cyt bo(3). PMID- 20351112 TI - Regulation of NT-PGC-1alpha subcellular localization and function by protein kinase A-dependent modulation of nuclear export by CRM1. AB - Peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) plays a central role in the regulation of cellular energy metabolism and metabolic adaptation to environmental and nutritional stimuli. We recently described a novel, biologically active splice variant of PGC-1alpha (NT-PGC 1alpha, amino acids 1-270) that retains the ability to interact with and transactivate nuclear hormone receptors through its N-terminal transactivation domain. Whereas PGC-1alpha is an unstable nuclear protein sensitive to ubiquitin mediated targeting to the proteasome, NT-PGC-1alpha is relatively stable and predominantly cytoplasmic, suggesting that its ability to interact with and activate nuclear receptors and transcription factors is dependent upon regulated access to the nucleus. We provide evidence that NT-PGC-1alpha interacts with the nuclear exportin, CRM1, through a specific leucine-rich domain (nuclear export sequence) that regulates its export to the cytoplasm. The nuclear export of NT PGC-1alpha is inhibited by protein kinase A-dependent phosphorylation of Ser-194, Ser-241, and Thr-256 on NT-PGC-1alpha, which effectively increases its nuclear concentration. Using site-directed mutagenesis to prevent or mimic phosphorylation at these sites, we show that the transcriptional activity of NT PGC-1alpha is regulated in part through regulation of its subcellular localization. These findings suggest that the function of NT-PGC-1alpha as a transcriptional co-activator is regulated by protein kinase A-dependent inhibition of CRM1-mediated export from the nucleus. PMID- 20351114 TI - The Drosophila copper transporter Ctr1C functions in male fertility. AB - Living organisms have evolved intricate systems to harvest trace elements from the environment, to control their intracellular levels, and to ensure adequate delivery to the various organs and cellular compartments. Copper is one of these trace elements. It is at the same time essential for life but also highly toxic, not least because it facilitates the generation of reactive oxygen species. In mammals, copper uptake in the intestine and copper delivery into other organs are mediated by the copper importer Ctr1. Drosophila has three Ctr1 homologs: Ctr1A, Ctr1B, and Ctr1C. Earlier work has shown that Ctr1A is an essential gene that is ubiquitously expressed throughout development, whereas Ctr1B is responsible for efficient copper uptake in the intestine. Here, we characterize the function of Ctr1C and show that it functions as a copper importer in the male germline, specifically in maturing spermatocytes and mature sperm. We further demonstrate that loss of Ctr1C in a Ctr1B mutant background results in progressive loss of male fertility that can be rescued by copper supplementation to the food. These findings hint at a link between copper and male fertility, which might also explain the high Ctr1 expression in mature mammalian spermatozoa. In both mammals and Drosophila, the X chromosome is known to be inactivated in the male germline. In accordance with such a scenario, we provide evidence that in Drosophila, the autosomal Ctr1C gene originated as a retrogene copy of the X-linked Ctr1A, thus maintaining copper delivery during male spermatogenesis. PMID- 20351113 TI - Identification of multiple rate-limiting steps during the human mitochondrial transcription cycle in vitro. AB - We have reconstituted human mitochondrial transcription in vitro on DNA oligonucleotide templates representing the light strand and heavy strand-1 promoters using protein components (RNA polymerase and transcription factors A and B2) isolated from Escherichia coli. We show that 1 eq of each transcription factor and polymerase relative to the promoter is required to assemble a functional initiation complex. The light strand promoter is at least 2-fold more efficient than the heavy strand-1 promoter, but this difference cannot be explained solely by the differences in the interaction of the transcription machinery with the different promoters. In both cases, the rate-limiting step for production of the first phosphodiester bond is open complex formation. Open complex formation requires both transcription factors; however, steps immediately thereafter only require transcription factor B2. The concentration of nucleotide required for production of the first dinucleotide product is substantially higher than that required for subsequent cycles of nucleotide addition. In vitro, promoter-specific differences in post-initiation control of transcription exist, as well as a second rate-limiting step that controls conversion of the transcription initiation complex into a transcription elongation complex. Rate limiting steps of the biochemical pathways are often those that are targeted for regulation. Like the more complex multisubunit transcription systems, multiple steps may exist for control of transcription in human mitochondria. The tools and mechanistic framework presented here will facilitate not only the discovery of mechanisms regulating human mitochondrial transcription but also interrogation of the structure, function, and mechanism of the complexes that are regulated during human mitochondrial transcription. PMID- 20351115 TI - The L-cysteine/L-cystine shuttle system provides reducing equivalents to the periplasm in Escherichia coli. AB - Intracellular thiols like L-cysteine and glutathione play a critical role in the regulation of cellular processes. Escherichia coli has multiple L-cysteine transporters, which export L-cysteine from the cytoplasm into the periplasm. However, the role of L-cysteine in the periplasm remains unknown. Here we show that an L-cysteine transporter, YdeD, is required for the tolerance of E. coli cells to hydrogen peroxide. We also present evidence that L-cystine, a product from the oxidation of L-cysteine by hydrogen peroxide, is imported back into the cytoplasm in a manner dependent on FliY, the periplasmic L-cystine-binding protein. Remarkably, this protein, which is involved in the recycling of the oxidized L-cysteine, is also found to be important for the hydrogen peroxide resistance of this organism. Furthermore, our analysis of the transcription of relevant genes revealed that the transcription of genes encoding FliY and YdeD is highly induced by hydrogen peroxide rather than by L-cysteine. These findings led us to propose that the inducible L-cysteine/L-cystine shuttle system plays an important role in oxidative stress tolerance through providing a reducing equivalent to the periplasm in E. coli. PMID- 20351116 TI - Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction. AB - Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2) adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant ( approximately 50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knock-out (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac beta adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and beta adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression. PMID- 20351117 TI - Time to move on from the euthanasia debate. PMID- 20351118 TI - Is deep vein thrombosis different during pregnancy? PMID- 20351119 TI - Stop the beef eaters, save the world. PMID- 20351120 TI - Simulation in surgical education. PMID- 20351121 TI - Anatomic distribution of deep vein thrombosis in pregnancy. AB - BACKGROUND: Prospective studies of nonpregnant patients have demonstrated that most deep vein thromboses of the lower extremity originate in the calf veins and progress proximally, but the anatomic distribution of thromboses in pregnant patients is unclear. An understanding of the anatomic distribution of deep vein thrombosis in pregnancy has important implications for optimizing diagnostic imaging protocols. We undertook this study to determine the anatomic distribution of deep vein thrombosis of the lower extremity in symptomatic pregnant patients. METHODS: We systematically searched MEDLINE (1966 to January 2009), Embase (1980 to January 2009) and the Cochrane Library using prespecified criteria to identify articles providing objective diagnostic and anatomic information for unselected or consecutive symptomatic pregnant patients with deep vein thrombosis. RESULTS: Six articles from an initial list of 1098 titles met the inclusion criteria. These articles provided information for 124 pregnant women with a diagnosis of deep vein thrombosis. Overall, involvement of the left leg was reported in 84 (88%) of the 96 patients for which the side affected was known, and 87 (71%) of 122 thromboses were restricted to the proximal veins without involvement of the calf veins. Among these cases of proximal deep vein thrombosis, 64% (56/87) were restricted to the iliac and/or femoral vein. CONCLUSION: Despite a paucity of studies in this area, the results of our review suggest that the anatomic distribution of deep vein thrombosis in pregnant women differs from that for nonpregnant patients. In addition to what was previously known--that left-sided deep vein thrombosis is more common in pregnancy--we also found that proximal deep vein thrombosis restricted to the femoral or iliac veins is also more common (> 60% of cases). If confirmed by larger studies, these findings could affect our understanding of the pathophysiology and derivation of diagnostic algorithms for examination of pregnant women with suspected deep vein thrombosis. PMID- 20351122 TI - Predicting potential survival benefit of renal transplantation in patients with chronic kidney disease. AB - BACKGROUND: To facilitate decision-making about treatment options for patients with end-stage renal disease considering kidney transplantation, we sought to develop an index for clinical prediction of risk for death. METHODS: We derived and validated a multivariable survival model predicting time to death in 169,393 patients with end-stage renal disease who were eligible for transplantation. We modified the model into a simple point-system index. RESULTS: Deaths occurred in 23.5% of the cohort. Twelve variables independently predicted death: age, race, cause of kidney failure, body mass index, comorbid disease, smoking, employment status, serum albumin level, year of first renal replacement therapy, kidney transplantation, time to transplant wait-listing and time on the wait list. The index separated patients into 26 groups having significantly unique five-year survival, ranging from 97.8% in the lowest-risk group to 24.7% in the highest risk group. The index score was discriminative, with a concordance probability of 0.746 (95% CI 0.741-0.751). Observed survival in the derivation and validation cohorts was similar for each level of index score in 93.9% of patients. INTERPRETATION: Our prognostic index uses commonly available information to predict mortality accurately in patients with end-stage renal disease. This index could provide valuable quantitative data on survival for clinicians and patients to use when deciding whether to pursue transplantation or remain on dialysis. PMID- 20351123 TI - The placement of nasogastric tubes. PMID- 20351124 TI - Collapse of a hockey player: ruptured aneurysm of the renal artery. PMID- 20351126 TI - Military ombudsman to again review mental health services. PMID- 20351127 TI - US health reform heads for legal showdown with states. PMID- 20351128 TI - Obama breaks a century's logjam. PMID- 20351129 TI - Electronic health records a "strong priority" for US government. PMID- 20351130 TI - Salves and silver bullets. PMID- 20351131 TI - Cancer symptom clusters: old concept but new data. AB - Individuals with cancer have multiple symptoms, which frequently co-occur. A nonrandom distribution of symptoms suggests a common mechanism. Symptom clusters (SCs) were considered part of various syndromes in the early years of medicine. The SC concept in clinical medicine is old. Symptom clusters were commonly described in the psychology/psychiatry and neurology literature. Symptom cluster may be defined either clinically or statistically. Statistically derived clusters can differ from clinically defined clusters. The clinical importance of statistically derived clusters is unclear. Pain-insomnia-fatigue and pain depression-fatigue are commonly recognized clinical clusters. Nausea-vomiting and anxiety-depression are also statistically observed clusters. The longitudinal stability of clusters is unknown. Certain SCs, appear to have a greater adverse influence on outcomes (such as performance status and survival) than others. Comorbidities probably influence symptoms at different levels, but their effect on cancer clusters is unknown. Comprehensive symptom assessment is crucial to cluster identification. The potential use of the cluster concept to abbreviate symptom assessment tools needs validation. Symptom cluster can be disease and/or treatment related and may change as individuals undergo antitumor therapies. Polypharmacy in symptom management is frequent but could be minimized if 1 drug could be used to treat cluster symptoms. Symptom cluster appears to vary with the assessment tool, disease stage, symptom domain used to cluster, cluster methodology, and number of symptoms assessed. The validity and reliability of SCs need universally accepted statistical methods, assessment tools, and symptom domains. For now, nausea-vomiting is recognized as a consistent cluster across multiple studies. Pain-depression-fatigue and pain-insomnia-fatigue are also well recognized. Symptom clusters may help in cancer diagnosis, symptom management, and prognostication. However, the cluster method, reliability, and validity need to be established before assessment or treatment guidelines are established. Symptom clusters require further research before becoming part of routine medical symptom assessment and management. PMID- 20351132 TI - End-of-life care when the state is the guardian. PMID- 20351133 TI - A comparative study of the modified Sauve-Kapandji procedure for rheumatoid wrist with and without stabilization of the proximal ulnar stump. AB - We compared the clinical and radiological results of the modified Sauve-Kapandji procedure for 41 of 86 operated rheumatoid wrists with (n=22) and without (n=19) stabilization of the proximal ulnar stump with a slip of half the extensor carpi ulnaris tendon. Gender, age, and follow-up period were similar in the two groups. We found no difference clinically or on radiographs between the two groups other than better early postoperative pain relief in those stabilized. Stabilization of the proximal ulnar stump may not be necessary in the modified Sauve-Kapandji procedure for rheumatoid wrists. PMID- 20351134 TI - Review: The intersection of surfactant homeostasis and innate host defense of the lung: lessons from newborn infants. AB - The study of pulmonary surfactant, directed towards prevention and treatment of respiratory distress syndrome in preterm infants, led to the identification of novel proteins/genes that determine the synthesis, packaging, secretion, function, and catabolism of alveolar surfactant. The surfactant proteins, SP-A, SP-B, SP-C, and SP-D, and the surfactant lipid associated transporter, ABCA3, play critical roles in surfactant homeostasis. The study of their structure and function provided insight into a system that integrates the biophysical need to reduce surface tension in the alveoli and the innate host defenses required to maintain pulmonary structure and function after birth. Alveolar homeostasis depends on the intrinsic, multifunctional structures of the surfactant-associated proteins and the shared transcriptional regulatory modules that determine both the expression of genes involved in surfactant production as well as those critical for host defense. Identification of the surfactant proteins and the elucidation of the genetic networks regulating alveolar homeostasis have provided the basis for understanding and diagnosing rare and common pulmonary disorders, including respiratory distress syndrome, inherited disorders of surfactant homeostasis, and pulmonary alveolar proteinosis. PMID- 20351135 TI - Sera from patients with Crohn's disease break bacterial lipopolysaccharide tolerance of human intestinal epithelial cells via MD-2 activity. AB - Myeloid differentiation (MD)-2 is linked to the cell surface as a Toll-like receptor (TLR) 4-bound protein though may also function as a soluble receptor to enable the lipopolysaccharide (LPS)-driven response. We recently demonstrated the importance of MD-2 either as a cell-associated or as a soluble receptor in the control of intestinal epithelial cell response toward LPS. High levels of circulating MD-2 were recently proposed as a risk factor for infectious/ inflammatory diseases as septic shock. We hypothesized that MD-2 might be present in sera from patients with inflammatory bowel disease and have pathogenic consequences. We analysed MD-2 activity in sera from patients with inflammatory bowel disease or from healthy subjects. We measured MD-2 activity as the capacity to mediate LPS-driven stimulation of intestinal epithelial cells (HT29). We found that sera from patients with inflammatory bowel disease, particularly Crohn's disease, endowed HT29 cells with a markedly higher LPS-dependent stimulating capacity as compared to sera from healthy subjects. The effect of sera was specific for LPS activation and was reduced in the presence of anti-MD-2, and anti-TLR4 antibodies. We conclude that sera from patients with inflammatory bowel disease might contain increased MD-2. This might result in higher local availability of the protein leading to a loss of tolerance toward gut microbiota. PMID- 20351136 TI - The Legionella pneumophila LetA/LetS two-component system exhibits rheostat-like behavior. AB - When confronted with metabolic stress, replicative Legionella pneumophila bacteria convert to resilient, infectious cells equipped for transmission. Differentiation is promoted by the LetA/LetS two-component system, which belongs to a family of signal-transducing proteins that employ a four-step phosphorelay to regulate gene expression. Histidine 307 of LetS was essential to switch on the transmission profile, but a threonine substitution at position 311 (T311M) suggested a rheostat-like function. The letS(T311M) bacteria resembled the wild type (WT) for some traits and letS null mutants for others, whereas they displayed intermediate levels of infectivity, cytotoxicity, and lysosome evasion. Although only 30 to 50% of letS(T311M) mutants became motile, flow cytometry determined that every cell eventually activated the flagellin promoter to WT levels, but expression was delayed. Likewise, letS(T311M) mutants exhibited delayed induction of RsmY and RsmZ, regulatory RNAs that relieve CsrA repression of transmission traits. Transcriptional profile analysis revealed that letS(T311M) mutants expressed the flagellar regulon and multiple other transmissive-phase loci at a higher cell density than the WT. Accordingly, we postulate that the letS(T311M) mutant may relay phosphate less efficiently than the WT LetS sensor protein, leading to sluggish gene expression and a variety of phenotypic profiles. Thus, as first described for BvgA/BvgS, rather than acting as on/off switches, this family of two-component systems exhibit rheostat activity that likely confers versatility as microbes adapt to fluctuating environments. PMID- 20351137 TI - Tetratricopeptide repeat protein-associated proteins contribute to the virulence of Porphyromonas gingivalis. AB - Porphyromonas gingivalis is one of the most etiologically important microorganisms in periodontal disease. We found in a previous study that PG1385 (TprA) protein, a tetratricopeptide repeat (TPR) protein, was upregulated in P. gingivalis wild-type cells placed in a mouse subcutaneous chamber and that a tprA mutant was clearly less virulent in the mouse subcutaneous abscess model (M. Yoshimura et al., Oral Microbiol. Immunol. 23:413-418, 2008). In the present study, we investigated the gene expression profile of tprA mutant cells placed in a mouse subcutaneous chamber and found that 9 genes, including PG2102 (tapA), PG2101 (tapB), and PG2100 (tapC) genes, were downregulated in the tprA mutant compared with those in the wild type. Expression of a cluster of tapA, tapB, and tapC genes of the mutant was also downregulated in an in vitro culture with enriched brain heart infusion medium. The TprA protein has three TPR motifs known as a protein-protein interaction module. Yeast two-hybrid system analysis and in vitro protein binding assays with immunoprecipitation and surface plasmon resonance detection revealed that the TprA protein could bind to TapA and TapB proteins. TprA and TapB proteins were located in the periplasmic space, whereas TapA, which appeared to be one of the C-terminal domain family proteins, was located at the outer membrane. We constructed tapA, tapB, and tapC single mutants and a tapA-tapB-tapC deletion mutant. In the mouse subcutaneous infection experiment, all of the mutants were less virulent than the wild type. These results suggest that TprA, TapA, TapB, and TapC are cooperatively involved in P. gingivalis virulence. PMID- 20351138 TI - Mitogen-activated protein kinase phosphatase 2 regulates the inflammatory response in sepsis. AB - Sepsis results from a dysregulation of the regulatory mechanisms of the pro- and anti-inflammatory response to invading pathogens. The mitogen-activated protein (MAP) kinase cascades are key signal transduction pathways involved in the cellular production of cytokines. The dual-specific phosphatase 1 (DUSP 1), mitogen-activated protein kinase phosphatase-1 (MKP-1), has been shown to be an important negative regulator of the inflammatory response by regulating the p38 and Jun N-terminal protein kinase (JNK) MAP kinase pathways to influence pro- and anti-inflammatory cytokine production. MKP-2, also a dual-specific phosphatase (DUSP 4), is a phosphatase highly homologous with MKP-1 and is known to regulate MAP kinase signaling; however, its role in regulating the inflammatory response is not known. We hypothesized a regulatory role for MKP-2 in the setting of sepsis. Mice lacking the MKP-2 gene had a survival advantage over wild-type mice when challenged with intraperitoneal lipopolysaccharide (LPS) or a polymicrobial infection via cecal ligation and puncture. The MKP-2(-/-) mice also exhibited decreased serum levels of both pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1beta [IL-1beta], IL-6) and anti-inflammatory cytokines (IL-10) following endotoxin challenge. Isolated bone marrow-derived macrophages (BMDMs) from MKP-2(-/-) mice showed increased phosphorylation of the extracellular signal-regulated kinase (ERK), decreased phosphorylation of JNK and p38, and increased induction of MKP-1 following LPS stimulation. The capacity for cytokine production increased in MKP-2(-/-) BMDMs following MKP-1 knockdown. These data support a mechanism by which MKP-2 targets ERK deactivation, thereby decreasing MKP-1 and thus removing the negative inhibition of MKP-1 on cytokine production. PMID- 20351139 TI - Cooperation between multiple microbial pattern recognition systems is important for host protection against the intracellular pathogen Legionella pneumophila. AB - Multiple pattern recognition systems have been shown to initiate innate immune responses to microbial pathogens. The degree to which these detection systems cooperate with each other to provide host protection is unknown. Here, we investigated the importance of several immune surveillance pathways in protecting mice against lethal infection by the intracellular pathogen Legionella pneumophila, the causative agent of a severe pneumonia called Legionnaires' disease. Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated against L. pneumophila in the lung. Elimination of Rip2 or Naip5/NLRC4 signaling in MyD88-deficient mice resulted in increased replication and dissemination of L. pneumophila and higher rates of mortality. Irradiated wild-type mice receiving bone marrow cells from pattern recognition receptor-deficient mice displayed L. pneumophila infection phenotypes similar to those of donor mice. Rip2 and Naip5/NLRC4 signaling provided additive effects in protecting MyD88-deficient mice from lethal infection by L. pneumophila, with the contribution of Naip5/NLRC4 being slightly greater than that of Rip2. Thus, activation of the Rip2, MyD88, and Naip5/NLRC4 signaling pathways triggers a coordinated and synergistic response that protects the host against lethal infection by L. pneumophila. These data provide new insight into how different pattern recognition systems interact functionally to generate innate immune responses that protect the host from lethal infection by activating cellular pathways that restrict intracellular replication of L. pneumophila and by recruiting to the site of infection additional phagocytes that eliminate extracellular bacteria. PMID- 20351140 TI - Gamma interferon produced by antigen-specific CD4+ T cells regulates the mucosal immune responses to Citrobacter rodentium infection. AB - Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4(+) T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-gamma)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4(+) T cells and macrophage phagocytosis were evaluated in the presence of IFN-gamma or IL-4 in vitro. IFN-gamma-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4(+) T cells. Furthermore, a deficiency in antigen-specific CD4(+) T-cell expressed IFN-gamma led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-gamma produced by antigen-specific CD4(+) T cells plays an important role in the defense against C. rodentium. PMID- 20351141 TI - Identification and characterization of two Bordetella avium gene products required for hemagglutination. AB - Bordetella avium causes bordetellosis in birds, a disease similar to whooping cough caused by Bordetella pertussis in children. B. avium agglutinates guinea pig erythrocytes via an unknown mechanism. Loss of hemagglutination ability results in attenuation. We report the use of transposon mutagenesis to identify two genes required for hemagglutination. The genes (hagA and hagB) were adjacent and divergently oriented and had no orthologs in the genomes of other Bordetella species. Construction of in-frame, unmarked mutations in each gene allowed examination of the role of each in conferring erythrocyte agglutination, explanted tracheal cell adherence, and turkey poult tracheal colonization. In all of the in vitro and in vivo assays, the requirement for the trans-acting products of hagA and hagB (HagA and HagB) was readily shown. Western blotting, using antibodies to purified HagA and HagB, revealed proteins of the predicted sizes of HagA and HagB in an outer membrane-enriched fraction. Antiserum to HagB, but not HagA, blocked B. avium erythrocyte agglutination and explanted turkey tracheal ring binding. Bioinformatic analysis indicated the similarity of HagA and HagB to several two-component secretory apparatuses in which one product facilitates the exposition of the other. HagB has the potential to serve as a useful immunogen to protect turkeys against colonization and subsequent disease. PMID- 20351142 TI - Genome-wide transposon mutagenesis reveals a role for pO157 genes in biofilm development in Escherichia coli O157:H7 EDL933. AB - Enterohemorrhagic Escherichia coli O157:H7, a world-wide human food-borne pathogen, causes mild to severe diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. The ability of this pathogen to persist in the environment contributes to its dissemination to a wide range of foods and food processing surfaces. Biofilms are thought to be involved in persistence, but the process of biofilm formation is complex and poorly understood in E. coli O157:H7. To better understand the genetics of this process, a mini-Tn5 transposon insertion library was constructed in strain EDL933 and screened for biofilm-negative mutants using a microtiter plate assay. Ninety-five of 11,000 independent insertions (0.86%) were biofilm negative, and transposon insertions were located in 51 distinct genes/intergenic regions that must be involved either directly or indirectly in biofilm formation. All of the 51 biofilm-negative mutants showed reduced biofilm formation on both hydrophilic and hydrophobic surfaces. Thirty-six genes were unique to this study, including genes on the virulence plasmid pO157. The type V secreted autotransporter serine protease EspP and the enterohemolysin translocator EhxD were found to be directly involved in biofilm formation. In addition, EhxD and EspP were also important for adherence to T84 intestinal epithelial cells, suggesting a role for these genes in tissue interactions in vivo. PMID- 20351143 TI - Biological characterization of Chlamydia trachomatis plasticity zone MACPF domain family protein CT153. AB - Chlamydia trachomatis strains are obligate intracellular human pathogens that share near genomic synteny but have distinct infection and disease organotropisms. The genetic basis for differences in the pathogen-host relationship among chlamydial strains is linked to a variable region of chlamydial genomes, termed the plasticity zone (PZ). Two groups of PZ-encoded proteins, the membrane attack complex/perforin (MACPF) domain protein (CT153) and members of the phospholipase D-like (PLD) family, are related to proteins that modify membranes and lipids, but the functions of CT153 and the PZ PLDs (pzPLDs) are unknown. Here, we show that full-length CT153 (p91) was present in the elementary bodies (EBs) of 15 C. trachomatis reference strains. CT153 underwent a rapid infection-dependent proteolytic cleavage into polypeptides of 57 and 41 kDa that was independent of de novo chlamydial protein synthesis. Following productive infection, p91 was expressed during the mid-developmental cycle and was similarly processed into p57 and p41 fragments. Infected-cell fractionation studies showed that insoluble fractions contained p91, p57, and p41, whereas only p91 was found in the soluble fraction, indicating that unprocessed CT153 may be secreted. Finally, CT153 localized to a distinct population of reticulate bodies, some of which were in contact with the inclusion membrane. PMID- 20351144 TI - Role of CD4+ and CD8+ T cells in clearance of primary pulmonary infection with Coxiella burnetii. AB - The mechanisms of the primary adaptive immune response to Coxiella burnetii are not well known. Following inoculation of the lungs with C. burnetii Nine Mile phase I (NMI), SCID mice developed pneumonia and splenomegaly and succumbed to infection, whereas wild-type mice cleared the infection by 24 days. SCID mice reconstituted with either CD4+ T cells or CD8+ T cells alone were able to control the infection, indicating that the presence of either type of T cells was sufficient to control infection, and B cells were not necessary for primary immunity. Similarly, wild-type mice depleted of either CD4+ T cells or CD8+ T cells controlled infections in their lungs, but these mice were highly susceptible if they were depleted of both types of T cells. However, compared to CD4+ T-cell-dependent protection, CD8+ T-cell-dependent protection resulted in less inflammation in the lungs and less growth of bacteria in the spleens. PMID- 20351145 TI - Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type 1. AB - Shiga toxins (Stxs) are bacterial cytotoxins produced by the enteric pathogens Shigella dysenteriae serotype 1 and some serotypes of Escherichia coli that cause bacillary dysentery and hemorrhagic colitis, respectively. To date, approaches to studying the capacity of Stxs to alter gene expression in intoxicated cells have been limited to individual genes. However, it is known that many of the signaling pathways activated by Stxs regulate the expression of multiple genes in mammalian cells. To expand the scope of analysis of gene expression and to better understand the underlying mechanisms for the various effects of Stxs on host cell functions, we carried out comparative microarray analyses to characterize the global transcriptional response of human macrophage-like THP-1 cells to Shiga toxin type 1 (Stx1) and lipopolysaccharides. The data were analyzed by using a rigorous combinatorial approach with three separate statistical algorithms. A total of 36 genes met the criteria of upregulated expression in response to Stx1 treatment, with 14 genes uniquely upregulated by Stx1. Microarray data were validated by real-time reverse transcriptase PCR for genes encoding early growth response 1 (Egr-1) (transcriptional regulator), cyclooxygenase 2 (COX-2; inflammation), and dual specificity phosphatase 1 (DUSP1), DUSP5, and DUSP10 (regulation of mitogen-activated protein kinase signaling). Stx1-mediated signaling through extracellular signal-regulated kinase 1/2 and Egr-1 appears to be involved in the increased expression and production of the proinflammatory mediator tumor necrosis factor alpha. Activation of COX-2 is associated with the increased production of proinflammatory and vasoactive eicosanoids. However, the capacity of Stx1 to increase the expression of genes encoding phosphatases suggests that mechanisms to dampen the macrophage proinflammatory response may be built into host response to the toxins. PMID- 20351146 TI - Alpha-galactosylceramide promotes killing of Listeria monocytogenes within the macrophage phagosome through invariant NKT-cell activation. AB - alpha-Galactosylceramide (alpha-GalCer) has been exploited for the treatment of microbial infections. Although amelioration of infection by alpha-GalCer involves invariant natural killer T (iNKT)-cell activation, it remains to be determined whether macrophages (Mphi) participate in the control of microbial pathogens. In the present study, we examined the participation of Mphi in immune intervention in infection by alpha-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal Mphi from C57BL/6 mice, but not iNKT cell deficient mice, were enhanced after intraperitoneal injection of alpha-GalCer despite the absence of iNKT cells in the peritoneal cavity. High levels of gamma interferon (IFN-gamma) and nitric oxide (NO) were detected in the peritoneal cavities of mice treated with alpha-GalCer and in culture supernatants of peritoneal Mphi from mice treated with alpha-GalCer, respectively. Although enhanced bactericidal activity of peritoneal Mphi by alpha-GalCer was abrogated by endogenous IFN-gamma neutralization, this was only marginally affected by NO inhibition. Similar results were obtained by using a listeriolysin O-deficient strain of Listeria monocytogenes. Moreover, respiratory burst in Mphi was increased after alpha-GalCer treatment. Our results suggest that amelioration of listeriosis by alpha-GalCer is, in part, caused by enhanced killing of L. monocytogenes within phagosomes of Mphi activated by IFN-gamma from iNKT cells residing in an organ(s) other than the peritoneal cavity. PMID- 20351147 TI - Chlamydia pneumoniae infection in polarized epithelial cell lines. AB - We set up a polarized cell culture model to study the pathogenicity of a common respiratory tract pathogen, Chlamydia pneumoniae. Immunofluorescence staining of ZO-1 (a tight junction protein) and Na(+)K(+) ATPase (a protein pump localized at the basolateral membrane in the polarized epithelial cells), as well as TER measurements, suggested that the filter-grown Calu-3 cells, but not the A549 cells, were polarized when grown on collagen-coated membranes. Both the flat and the filter-grown cultures were infected with C. pneumoniae. Infection in the polarized Calu-3 cultures produced more C. pneumoniae genome equivalents than infection in the flat cultures. However, this progeny was not as infective as that in the flat cultures. The maximum amount of C. pneumoniae was detected at 6 days postinfection in the filter-grown A549 cells, indicating a slower developmental cycle than that observed in the flat A549 cultures. The effect of cycloheximide on the growth of C. pneumoniae in the polarized cells was negligible. Furthermore, the infection in the polarized Calu-3 cells was resistant to doxycycline, and several cytokines were released mainly on the apical side of the polarized cells in response to C. pneumoniae infection. These findings indicate that the growth of chlamydiae was altered in the filter-grown epithelial culture system. The diminished production of infective progeny of C. pneumoniae, together with the resistance to doxycycline and polarized secretion of cytokines from the infected Calu-3 cells, suggests that this model is useful for examining epithelial cell responses to C. pneumoniae infection, and it might better resemble in vivo infection in respiratory epithelial cells. PMID- 20351149 TI - "There is nothing like looking, if you want to find something" - asking questions and searching for answers - the evidence based approach. AB - Evidence based medicine (EBM) consists of four separate processes. Asking a clinical question Locating the evidence Appraising and synthesizing the evidence Applying the evidence Most people are familiar with the third step but not so familiar with the first two. Well-designed clinical questions can help clarify in a clinicians mind exactly what information is being sought and also help with the search. This clinical question can be framed around the PICO format. With a well structured PICO information can then be located in a timely manner using the concept of Haynes's 5 S's and a range of websites including trial registers and meta-search engines. PMID- 20351150 TI - An approach to the diagnosis of inherited metabolic disease. PMID- 20351151 TI - Spine and spinal cord tumours in children: a diagnostic and therapeutic challenge to healthcare systems. AB - Only 2% of childhood tumours occur in the spine and spinal cord; yet these tumours account for a disproportionate degree of morbidity in children with cancer. Spine and spinal cord tumours frequently initially present with non specific symptoms such as back pain and clumsiness and are therefore often associated with a prolonged period between symptom onset and diagnosis. Many children present repeatedly to healthcare services before a diagnosis is made. and appropriate imaging is often only instigated once a child has developed neurological deficits. Unfortunately, despite treatment, these deficits are often only at best partially reversible. This article reviews the pathology and presentation of spine and spinal cord tumours in children and advises on the appropriate assessment of a child who may have a spine or spinal cord tumour. The principles underlying the management of these tumours are discussed and the management strategies for individual tumour types summarised. PMID- 20351152 TI - How to use: C-reactive protein. AB - C-reactive protein (CRP) is an acute-phase protein that increases 4-6 h after an inflammatory trigger and peaks at 36-50 h. Levels decrease rapidly with the resolution of inflammation. CRP is generally highly elevated in invasive bacterial infections and is often used as a marker of inflammation. A single CRP level is neither sensitive nor specific enough to identify all children with serious bacterial infection. However, a raised CRP does suggest serious bacterial infection and should suggest further assessment is needed. CRP levels that fail to decrease, or continue to rise, after 48 h of antibiotic therapy suggest treatment failure. In infants with suspected neonatal sepsis, two CRP measurements 24 h apart that are <10 mg/l are useful in excluding sepsis. PMID- 20351153 TI - A symptomatic journey to the centre of the brain. PMID- 20351154 TI - Evidence and the patient's role in safer care. PMID- 20351155 TI - Maternity care models in a remote and rural network: assessing clinical appropriateness and outcome indicators. AB - BACKGROUND: Little is known about performance of small rural maternity units, including stand-alone midwife units. AIM: To describe the proportions of women delivering locally, clinical appropriateness of model of care at delivery and outcome indicators for three rural staffing models of care. DESIGN: Case note review. SETTING: Remote and rural maternity units in NHS North of Scotland Region. SUBJECTS AND METHODS: 1400 deliveries to women from the catchments of eight rural units (stratified by staffing model) included those in local rural units and in associated distant referral units. Descriptive analysis examined women's risk, clinical appropriateness of model of care at delivery and outcomes aggregated by local catchment unit type and delivery unit type. RESULTS: Local deliveries by staffing model were 31% (214/697) in midwife stand-alone units, 70% (236/336) in midwife units alongside non-obstetric medical support and 86% (317/367) in small obstetric-led units. Model of care at delivery was generally appropriate according to risk. Judged inappropriate were 3% (22/696) of women with complications delivering in midwife stand-alone units; and of referral unit deliveries, 6% (37/632) with suspected complications unconfirmed, plus 5% (31/633) discharged undelivered by referral hospital at >36 weeks' gestation. Risk profiles of catchment samples were similar, but caesarean section rates appeared lower and neonatal unit admissions higher for women from stand-alone midwife units. CONCLUSIONS: Rural women were generally referred appropriately for specialist care. These stand-alone midwife units provided intrapartum care for approximately one-third of rural women who remained without complications. Further evidence is needed about outcomes by staffing models of care. PMID- 20351156 TI - Local guidelines for the transfer of women from midwifery unit to obstetric unit during labour in England: a systematic appraisal of their quality. AB - BACKGROUND: A proportion of women planning to give birth in a midwifery unit will experience complications during labour that necessitate transfer to an obstetric unit. Local guidelines for the transfer of women in labour have the potential to impact on quality of care and the safety of the transfer process. OBJECTIVE: To systematically appraise the quality of local NHS guidelines on the transfer of women from midwifery unit to obstetric unit during labour. METHODS: Guidelines were requested from all 52 NHS hospital trusts in England with midwifery units. The Appraisal of Guidelines for Research and Evaluation Instrument was used to evaluate the quality of the guidelines received. RESULTS: Relevant guidelines were received from 34 (65%) trusts. No guidelines scored on the 'editorial independence' domain. The mean score on 'scope and purpose' (56.2%), concerned with the aims, clinical questions and target patient population of the guideline, was higher than for other domains: 'clarity and presentation' (language and format) 45.3%, 'stakeholder involvement' (representation of users' views) 15.3%, 'rigour of development' (process used to develop guideline) 15.0%, 'applicability' (organisational, behavioural and cost implications of applying guideline) 7.1%. Only three guidelines were recommended for use in clinical practice. CONCLUSIONS: We believe this to be the first systematic appraisal of the quality of local NHS guidelines. Overall these local guidelines were of poor quality. It is not clear whether the quality of these midwifery guidelines is typical of local guidelines in other clinical areas, but this study raises fundamental questions about the appropriate development of high-quality local clinical guidelines. PMID- 20351157 TI - Real-time clinical alerting: effect of an automated paging system on response time to critical laboratory values--a randomised controlled trial. AB - BACKGROUND: Timely and reliable communication of critical laboratory values is a Joint Commission National Patient Safety Goal. The objective was to evaluate the effect of an automated system for paging critical values directly to the responsible physician. METHODS: A randomised controlled trial on the general medicine clinical teaching units at an urban academic hospital was conducted from February to May 2006; the unit of randomisation was the critical laboratory value. The intervention was an automated paging system that sent the critical value directly to the responsible physician's pager. The control arm was usual care, which was a telephone call to the patient's ward by the laboratory technician. The primary outcome was response time, defined as the interval between acceptance of the critical value into the laboratory information system to the writing of an order on the patient's chart in response to the critical value. If the time of order was not documented, the time of administration of treatment was used to calculate response time. RESULTS: For primary analysis, 165 critical values were evaluated on 108 patients with full response time data. The median response time was 16 min (IQR 2-141) for the automated paging group and 39.5 min (IQR 7-104.5) for the usual care group (p=0.33). CONCLUSIONS: The automated paging system reduced the length of time physicians took to respond to critical laboratory values, but this difference was not statistically significant. Future reseach should evaluate the effects of alerts for conditions that currently do not generate a phone call and the addition of real-time decision support to the critical value alerts. PMID- 20351158 TI - Quality assessment in surgical care departments: proposal for a scoring system in terms of structure and process. AB - OBJECTIVE: To build a score able to reflect and rank surgical departments according to a definition of "quality" in terms of structure and process. METHODS: Collaborative design of a quality score in the framework of the French clinical research project NosoQual. Feasibility and observational study in 46 surgical departments visited between November 2002 and March 2003 according to standardised procedures. A bibliographic review followed by expert consultations, a field test, analysis and a final reconsideration leading to the definition of a consensual score. RESULTS: 138 variables comprised the score. They were classified into seven dimensions, each representing a different aspect of quality of care in surgery. According to the threshold and weight attributed to every variable, scores were calculated for each department. The average level of achievement of the scores varied from 42% to 71% of theoretical maxima. The variability of the scores related to the seven dimensions was larger and more significant than the one expressed by the overall score (coefficient of variation=0.1). CONCLUSION: This analytical work contributed to the design of a quality score for surgery. However, the progress of the score should continue to take into account all the obstacles that were observed and to meet the high requirements of the actual patient safety issue. PMID- 20351159 TI - Teamwork on inpatient medical units: assessing attitudes and barriers. AB - BACKGROUND: Discrepant attitudes about teamwork among nurses and physicians exist in operating rooms and intensive care units. Little is known about teamwork attitudes on general medical services. OBJECTIVE: To assess ratings of teamwork by providers on inpatient medical units and barriers to collaboration. DESIGN AND PARTICIPANTS: Nurses, primary hospital physicians and medical subspeciality consultants on four general medical units were surveyed. MEASUREMENTS: Providers rated the quality of communication and collaboration experienced with their own and other disciplines. Providers also rated potential barriers to collaboration. Differences between providers in ratings of collaboration and barriers were tested using analysis of variance. RESULTS: Of 230 eligible providers, 159 (69%) completed the survey. Teamwork ratings of nurses were similarly high across provider types. Ratings of physicians differed considerably by provider type (pe' salt bridge with Lys268 that increases attractive electrostatic interactions between paired leucine zippers and promotes homodimerization. Mutating Ser273 to Ala or Lys268 to Glu decreased C/EBPbeta homodimer formation, whereas heterodimerization with C/EBPgamma was relatively unaffected. The S273A substitution also reduced the antiproliferative activity of C/EBPbeta in Ras(V12)-expressing fibroblasts and decreased binding to target cell cycle genes, while a phosphomimetic substitution (S273D) maintained growth arrest function. Our findings identify four novel C/EBPbeta-activating modifications, including RSK-mediated phosphorylation of a bifunctional residue in the leucine zipper that regulates DNA binding and homodimerization and thereby promotes cell cycle arrest. PMID- 20351174 TI - skn-1-Dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans. AB - Maintenance of a stable, properly folded, and catalytically active proteome is a major challenge to organisms in the face of multiple internal and external stresses which damage proteins and lead to protein misfolding. Here we show that internal metabolic stress produced by reactive intermediates resulting from tyrosine degradation triggers the expression of the aip-1 gene, which is critical in responses to the environmental toxin arsenic and the clearance of unstable polyglutamine and Abeta proteins. aip-1 acts via binding to the proteosome and enhancing proteosomal function. We find that full induction of aip-1 depends on the oxidative-stress-responsive skn-1 transcription factor but significant induction still occurs without skn-1. Importantly, activation of skn-1 with wdr 23(RNAi), which dramatically induces the expression of other skn-1 target genes, produces a minimal increase in aip-1 expression. This suggests that the previously demonstrated specificity in aip-1/AIRAP induction could reflect the actions of multiple synergistic activators, such as the heat shock factor homolog hsf-1, which we also find is required for full induction. These may be triggered by proteosome dysfunction, as we find that this event links the multiple inducers of aip-1. Together, our results show that cell stress triggers aip-1 expression by both skn-1-dependent and -independent pathways. PMID- 20351175 TI - Genetic analysis of hierarchical regulation for Gata1 and NF-E2 p45 gene expression in megakaryopoiesis. AB - GATA1 and NF-E2 p45 are two important regulators of megakaryopoiesis. Whereas GATA1 is known to regulate the p45 gene, details of the GATA1 contribution to the spatiotemporal expression of the p45 gene remain to be elucidated. To clarify the relationship between GATA1 and p45, we performed genetic complementation rescue analysis of p45 function in megakaryocytes utilizing the hematopoietic regulatory domain of the Gata1 gene (G1HRD). We established transgenic mouse lines expressing p45 under G1HRD regulation and crossed the mice with p45-null mice. Compound mutant mice displayed normal platelet counts and no sign of hemorrhage, indicating that G1HRD has the ability to express p45 in a spatiotemporally correct manner. However, deletion of 38 amino acids from the N-terminal region of p45 abrogated the p45 rescue function, suggesting the presence of an essential transactivation activity in the region. We then crossed the G1HRD-p45 transgenic mice with megakaryocyte-specific Gata1 gene knockdown (Gata1(Delta)(neo)(Delta)(HS)) mice. The G1HRD-p45 transgene was insufficient for complete rescue of the Gata1(Delta)(neo)(Delta)(HS) megakaryocytes, suggesting that GATA1 or other factors regulated by GATA1 are required to cooperate with p45 for normal megakaryopoiesis. This study thus provides a unique in vivo validation of the hierarchical relationship between GATA1 and p45 in megakaryocytes. PMID- 20351176 TI - DDB2, an essential mediator of premature senescence. AB - Reactive oxygen species (ROS) is critical for premature senescence, a process significant in tumor suppression and cancer therapy. Here, we reveal a novel function of the nucleotide excision repair protein DDB2 in the accumulation of ROS in a manner that is essential for premature senescence. DDB2-deficient cells fail to undergo premature senescence induced by culture shock, exogenous oxidative stress, oncogenic stress, or DNA damage. These cells do not accumulate ROS following DNA damage. The lack of ROS accumulation in DDB2 deficiency results from high-level expression of the antioxidant genes in vitro and in vivo. DDB2 represses antioxidant genes by recruiting Cul4A and Suv39h and by increasing histone-H3K9 trimethylation. Moreover, expression of DDB2 also is induced by ROS. Together, our results show that, upon oxidative stress, DDB2 functions in a positive feedback loop by repressing the antioxidant genes to cause persistent accumulation of ROS and induce premature senescence. PMID- 20351178 TI - Recruitment of polycomb complexes: a role for SCM. PMID- 20351177 TI - Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo. AB - The H/ACA motif of human telomerase RNA (hTR) directs specific pathways of endogenous telomerase holoenzyme assembly, function, and regulation. Similarities between hTR and other H/ACA RNAs have been established, but differences have not been explored even though unique features of hTR H/ACA RNP assembly give rise to telomerase deficiency in human disease. Here, we define hTR H/ACA RNA and RNP architecture using RNA accumulation, RNP affinity purification, and primer extension activity assays. First, we evaluate alternative folding models for the hTR H/ACA motif 5' hairpin. Second, we demonstrate an unanticipated and surprisingly general asymmetry of 5' and 3' hairpin requirements for H/ACA RNA accumulation. Third, we establish that hTR assembles not one but two sets of all four of the H/ACA RNP core proteins, dyskerin, NOP10, NHP2, and GAR1. Fourth, we address a difference in predicted specificities of hTR association with the holoenzyme subunit WDR79/TCAB1. Together, these results complete the analysis of hTR elements required for active RNP biogenesis and define the interaction specificities and stoichiometries of all functionally essential human telomerase holoenzyme subunits. This study uncovers unexpected similarities but also differences between telomerase and other H/ACA RNPs that allow a unique specificity of telomerase biogenesis and regulation. PMID- 20351179 TI - The calcium-dependent interaction between S100B and the mitochondrial AAA ATPase ATAD3A and the role of this complex in the cytoplasmic processing of ATAD3A. AB - S100 proteins comprise a multigene family of EF-hand calcium binding proteins that engage in multiple functions in response to cellular stress. In one case, the S100B protein has been implicated in oligodendrocyte progenitor cell (OPC) regeneration in response to demyelinating insult. In this example, we report that the mitochondrial ATAD3A protein is a major, high-affinity, and calcium-dependent S100B target protein in OPC. In OPC, ATAD3A is required for cell growth and differentiation. Molecular characterization of the S100B binding domain on ATAD3A by nuclear magnetic resonance (NMR) spectroscopy techniques defined a consensus calcium-dependent S100B binding motif. This S100B binding motif is conserved in several other S100B target proteins, including the p53 protein. Cellular studies using a truncated ATAD3A mutant that is deficient for mitochondrial import revealed that S100B prevents cytoplasmic ATAD3A mutant aggregation and restored its mitochondrial localization. With these results in mind, we propose that S100B could assist the newly synthesized ATAD3A protein, which harbors the consensus S100B binding domain for proper folding and subcellular localization. Such a function for S100B might also help to explain the rescue of nuclear translocation and activation of the temperature-sensitive p53val135 mutant by S100B at nonpermissive temperatures. PMID- 20351180 TI - The SANT domain of p400 ATPase represses acetyltransferase activity and coactivator function of TIP60 in basal p21 gene expression. AB - The TIP60 histone acetyltransferase plays diverse roles in DNA damage responses, DNA double-strand break repair, and transcriptional regulation. TIP60 resides within a multisubunit complex that has been shown to be targeted by transcription factors and to be involved in histone acetylation and transcriptional activation. p400, an SWI2/SNF2-related ATPase that serves as an ATP-dependent chromatin remodeling enzyme, exists as an integral subunit of a TIP60 complex but also resides within a distinct complex that presumably lacks TIP60 and appears to be involved in the transcriptional repression of basal p53 target gene expression. Here, we describe a TIP60-containing p400 complex population in which the acetyltransferase activity of TIP60 is repressed by interactions with p400. We further show that an SWI3-ADA2-N-CoR-TFIIIB (SANT) domain of p400 binds directly to the histone acetyltransferase (HAT) domain of TIP60 and blocks both its enzymatic activity and its coactivator function in regulating basal p21 gene expression. Our results thus suggest that p400 represses basal p21 gene expression through dual mechanisms that include the direct inhibition of TIP60 enzymatic activity described here and the previously described ATP-dependent positioning of H2A.Z at the promoter. PMID- 20351182 TI - Notch2 signaling is required for potent antitumor immunity in vivo. AB - CD8(+) T cells play a central role in cancer immunosurveillance, and the efficient induction of CTLs against tumor Ags is required for successful immunotherapy for cancer patients. Notch signaling directly regulates the transcription of effector molecules in CTLs. However, it remains unclear whether Notch signaling in CD8(+) T cells is required for antitumor CTL responses and whether modulation of Notch signaling can augment antitumor CTL responses. In this study, we demonstrate that signaling by Notch2 but not Notch1 in CD8(+) T cells is required for antitumor CTL responses. Notch2(flox/flox) mice crossed with E8I-cre transgenic (N2F/F-E8I) mice, in which the Notch2 gene is absent only in CD8(+) T cells, die earlier than control mice after inoculation with OVA expressing EG7 thymoma cells. In contrast, Notch1(flox/flox) mice crossed with E8I-cre transgenic mice inoculated with EG7 cells die comparable to control mice, indicating that Notch2 is crucial for exerting antitumor CTL responses. Injection of anti-Notch2 agonistic Ab or delta-like 1-overexpressing dendritic cells augmented the antitumor response in C57BL/6 mice inoculated with EG7 cells. These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses. PMID- 20351183 TI - Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice. AB - CD4(+) T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN gamma in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-gamma, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17(-/-) mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology. PMID- 20351181 TI - Comparative analysis of chromatin binding by Sex Comb on Midleg (SCM) and other polycomb group repressors at a Drosophila Hox gene. AB - Sex Comb on Midleg (SCM) is a transcriptional repressor in the Polycomb group (PcG), but its molecular role in PcG silencing is not known. Although SCM can interact with Polycomb repressive complex 1 (PRC1) in vitro, biochemical studies have indicated that SCM is not a core constituent of PRC1 or PRC2. Nevertheless, SCM is just as critical for Drosophila Hox gene silencing as canonical subunits of these well-characterized PcG complexes. To address functional relationships between SCM and other PcG components, we have performed chromatin immunoprecipitation studies using cultured Drosophila Schneider line 2 (S2) cells and larval imaginal discs. We find that SCM associates with a Polycomb response element (PRE) upstream of the Ubx gene which also binds PRC1, PRC2, and the DNA binding PcG protein Pleiohomeotic (PHO). However, SCM is retained at this Ubx PRE despite genetic disruption or knockdown of PHO, PRC1, or PRC2, suggesting that SCM chromatin targeting does not require prior association of these other PcG components. Chromatin immunoprecipitations (IPs) to test the consequences of SCM genetic disruption or knockdown revealed that PHO association is unaffected, but reduced levels of PRE-bound PRC2 and PRC1 were observed. We discuss these results in light of current models for recruitment of PcG complexes to chromatin targets. PMID- 20351184 TI - IL-17 enhancement of the IL-6 signaling cascade in astrocytes. AB - Astrocytes have important physiological roles in CNS homeostasis and serve as a bridge between the CNS and immune system. IL-17 and IL-6 are important in many CNS disorders characterized by neuroinflammation. We examined the role of IL-17 on the IL-6 signaling cascade in primary astrocytes. IL-17 functioned in a synergistic manner with IL-6 to induce IL-6 expression in astrocytes. The synergistic effect involved numerous signaling pathways including NF-kappaB, JNK MAPK, and p38 MAPK. The NF-kappaB pathway inhibitor BAY-11, JNK inhibitor JNKi II, and p38 inhibitor SB203580 suppressed the synergistic effect of IL-6 and IL 17 on IL-6 expression. IL-17 synergized with IL-6 to enhance the recruitment of activated NF-kappaB p65, c-Fos, c-Jun, and the histone acetyltransferases CREB binding protein and p300 to the IL-6 promoter in vivo to induce IL-6 transcription. This was accompanied by enhanced acetylation of histones H3 and H4 on the IL-6 promoter. Moreover, we elucidated an important role for suppressor of cytokine signaling (SOCS) 3 in IL-17 enhancement of IL-6 signaling in astrocytes. SOCS3 small interfering RNA knockdown and SOCS3 deletion in astrocytes augmented the synergistic effect of IL-6 and IL-17 due to an enhancement of activation of the NF-kappaB and MAPK pathways. These results indicate that astrocytes can serve as a target of Th17 cells and IL-17 in the CNS, and SOCS3 participates in IL-17 functions in the CNS as a negative feedback regulator. PMID- 20351186 TI - Activation of naive NK cells in response to Listeria monocytogenes requires IL-18 and contact with infected dendritic cells. AB - The mechanisms for NK cell activation during infection by intracellular bacterial pathogens are not clearly defined. To dissect how Listeria monocytogenes infection elicits NK cell activation, we evaluated the requirements for activation of naive splenic NK cells by infected bone marrow-derived dendritic cells (BMDCs). We found that NK cell activation in this setting required infection of BMDCs by live wild type bacteria. NK cells were not activated when BMDCs were infected with a live hemolysin deficient (Deltahly) strain. Neutralization of IL-12, TNF-alpha, or caspase-1 each dramatically reduced NK cell IFN-gamma production in response to live wt L. monocytogenes infection. Addition of recombinant IL-18, but not IL-1beta, reversed the effects of caspase 1 inhibition. Recombinant IL-18 also restored NK cell activation by BMDCs infected with Deltahly L. monocytogenes, which produced IL-12 but not IL-18. IL 18 acted on NK cells because MyD88 expression was required in responding NK cells, but not infected BMDC. However, secreted cytokines were not sufficient for activation of naive NK cells by infected BMDCs. Rather, NK cell activation additionally required contact between infected BMDCs and NK cells. These data suggest that the activation of NK cells during L. monocytogenes infection requires both secreted cytokines and ligation of NK activating receptors during direct contact with infected DCs. PMID- 20351185 TI - Impaired germinal center responses and suppression of local IgG production during intracellular bacterial infection. AB - Germinal centers (GCs) are specialized microenvironments in secondary lymphoid organs that facilitate the development of high-affinity, isotype-switched Abs, and immunological memory; consequently, many infections require GC-derived IgG for pathogen clearance. Although Ehrlichia muris infection elicits a robust expansion of splenic, IgM-secreting plasmablasts, we detected only very low frequencies of isotype-switched IgG-secreting cells in mouse spleens, until at least 3 wk postinfection. Instead, Ag-specific IgG was produced in lymph nodes, where it required CD4 T cell help. Consistent with these findings, organized GCs and phenotypically defined splenic GC B cells were found in lymph nodes, but not spleens. Ehrlichial infection also inhibited spleen IgG responses against a coadministered T cell-dependent Ag, hapten 4-hydroxy-3-nitrophenyl acetyl (NP) conjugated chicken gamma globulin in alum. NP-specific B cells failed to undergo expansion and differentiation into GC B cells in the spleen, Ab titers were reduced, and splenic IgG production was inhibited nearly 10-fold when the Ag was administered during infection. Our data provide a mechanism whereby an intracellular bacterial infection can compromise local immunity to coinfecting pathogens or antigenic challenge. PMID- 20351187 TI - The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. AB - Knowing the inherent stimulatory properties of the lipid moiety of bacterial lipoproteins, we first hypothesized that Brucella abortus outer membrane protein (Omp)16 lipoprotein would be able to elicit a protective immune response without the need of external adjuvants. In this study, we demonstrate that Omp16 administered by the i.p. route confers significant protection against B. abortus infection and that the protective response evoked is independent of the protein lipidation. To date, Omp16 is the first Brucella protein that without the requirement of external adjuvants is able to induce similar protection levels to the control live vaccine S19. Moreover, the protein portion of Omp16 (unlipidated Omp16 [U-Omp16]) elicits a protective response when administered by the oral route. Either systemic or oral immunization with U-Omp16 elicits a Th1-specific response. These abilities of U-Omp16 indicate that it is endowed with self adjuvanting properties. The adjuvanticity of U-Omp16 could be explained, at least in part, by its capacity to activate dendritic cells in vivo. U-Omp16 is also able to stimulate dendritic cells and macrophages in vitro. The latter property and its ability to induce a protective Th1 immune response against B. abortus infection have been found to be TLR4 dependent. The facts that U-Omp16 is an oral protective Ag and possesses a mucosal self-adjuvanting property led us to develop a plant-made vaccine expressing U-Omp16. Our results indicate that plant expressed recombinant U-Omp16 is able to confer protective immunity, when given orally, indicating that a plant-based oral vaccine expressing U-Omp16 could be a valuable approach to controlling this disease. PMID- 20351188 TI - Premature terminal exhaustion of Friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors. AB - During chronic viral infection, persistent exposure to viral Ags leads to the overexpression of multiple inhibitory cell-surface receptors that cause CD8(+) T cell exhaustion. The severity of exhaustion correlates directly with the level of infection and the number and intensity of inhibitory receptors expressed, and it correlates inversely with the ability to respond to the blockade of inhibitory pathways. Friend virus (FV) is a murine retrovirus complex that induces acute high-level viremia, followed by persistent infection and leukemia development, when inoculated into immunocompetent adult mice. In this article, we provide conclusive evidence that FV infection results in the generation of virus-specific effector CD8(+) T cells that are terminally exhausted. Acute FV-induced disease is characterized by a rapid increase in the number of virus-infected erythroblasts, leading to massive splenomegaly. Most of the expanded erythroblasts strongly express programmed death ligand-1 and MHC class I, thereby creating a highly tolerogenic environment. Consequently, FV-specific effector CD8(+) T cells uniformly express multiple inhibitory receptors, such as programmed cell death 1 (PD-1), T cell Ig domain and mucin domain 3 (Tim-3), lymphocyte activation gene-3, and CTLA-4, rapidly become nonresponsive to restimulation and are no longer reinvigorated by combined in vivo blockade of PD 1 and Tim-3 during the memory phase. However, combined blockade of PD-1 and Tim-3 during the priming/differentiation phase rescued FV-specific CD8(+) T cells from becoming terminally exhausted, resulting in improved CD8(+) T cell functionality and virus control. These results highlight FV's unique ability to evade virus specific CD8(+) T cell responses and the importance of an early prophylactic approach for preventing terminal exhaustion of CD8(+) T cells. PMID- 20351189 TI - Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation induced cell death. AB - Agonistic anti-CD137 mAbs either positively or negatively regulate T cell function. When administered at the beginning of lymphocytic choriomeningitis virus Armstrong infection anti-CD137 induced immunosuppression and T cell deletion, and in the case of influenza infection led to increased mortality. In contrast, 72 h delay in anti-CD137 treatment led to an enhanced virus-specific CD8 T cell response and rapid viral clearance. Virus-specific CD8 T cells in anti CD137-injected mice rapidly upregulate Fas expression, and although necessary, was insufficient to induce CD8 T cell deletion. Strikingly, CD137 signaling in T cells was found to be insufficient to induce suppression or deletion. Rather, immunosuppression and T cell deletion was only observed if CD137 signals were provided to T cells and dendritic cells (DCs). In vitro CD137 crosslinking in DCs led to phosphorylation of Stat3, and importantly, anti-CD137 treatment of lymphocytic choriomeningitis virus Armstrong infected Stat3 conditional knock-out mice induced neither immune suppression or T cell deletion. Taken together, these data suggest that CD137 signaling in DCs can regulate CD8 T cell survival through a Stat3 and Fas-mediated pathway. PMID- 20351190 TI - Alterations in ceramide concentration and pH determine the release of reactive oxygen species by Cftr-deficient macrophages on infection. AB - We recently demonstrated that the accumulation of ceramide in Cftr-deficient epithelial cells is important for the pathophysiology of CF. However, the role of ceramide in other lung cells, particularly lung macrophages, requires definition. In this study, we report that ceramide is accumulated in Cftr-deficient lung macrophages. Alveolar macrophages contain a vesicle population, which is stained with LysoSensor probes but not by tetramethylrhodamine dextran. These vesicles, presumably secretory lysosomes, exhibit a higher pH in Cftr-deficient macrophages than the corresponding vesicles in lung macrophages isolated from wild-type (WT) mice. Alkalinization of these vesicles in Cftr-deficient macrophages correlates with a failure of the macrophages to respond to infection with various Pseudomonas aeruginosa strains by acutely activating acid sphingomyelinase, releasing ceramide, forming ceramide-enriched membrane platforms that serve to cluster gp91(phox), and, most importantly, releasing reactive oxygen species (ROS). In contrast, these events occur rapidly in WT lung macrophages postinfection. Inhibiting ROS in WT macrophages prevents the killing of P. aeruginosa. These findings provide evidence for a novel pH-controlled pathway from acid sphingomyelinase activation via ceramide and clustering of gp91(phox) to the release of ROS in lung macrophages. PMID- 20351191 TI - Langerhans cells prime IL-17-producing T cells and dampen genital cytotoxic responses following mucosal immunization. AB - Langerhans cells (LCs) are dendritic cells (DCs) localized in stratified epithelia, such as those overlaying skin, buccal mucosa, and vagina. The contribution of LCs to the promotion or control of immunity initiated at epithelial sites remains debated. We report in this paper that an immunogen comprising OVA linked to the B subunit of cholera toxin, used as delivery vector, was efficient to generate CTLs after vaginal immunization. Using Lang-EGFP mice, we evaluated the contribution of distinct DC subsets to the generation of CD4 and CD8 T cell responses. We demonstrate that the vaginal epithelium, unlike the skin epidermis, includes a minor population of LCs and a major subset of langerin(-) DCs. Intravaginally administered Ag is taken up by LCs and langerin(-) DCs and carried up to draining lymph nodes, where both subsets prime CD8 T cells, unlike blood-derived DCs, although with distinct capabilities. LCs prime CD8 T cells with a cytokine profile dominated by IL-17, whereas Lang(-) DCs induce IFN-gamma producing T cells. Using Lang-DTR-EGFP mice to ensure a transient ablation of LCs, we found that these cells not only are dispensable for the generation of genital CTL responses but also downregulate these responses, by a mechanism that may involve IL-10 and IL-17 cytokines. This finding has implications for the development of mucosal vaccines and immunotherapeutic strategies designed for the targeting of DCs. PMID- 20351192 TI - Functional characterization of the recombinant human C1 inhibitor serpin domain: insights into heparin binding. AB - Variants of the human C1 inhibitor serpin domain containing three N-linked carbohydrates at positions 216, 231, and 330 (C1inhDelta97), a single carbohydrate at position 330 (C1inhDelta97DM), or no carbohydrate were produced in a baculovirus/insect cells system. An N-terminally His-tagged C1inhDelta97 variant was also produced. Removal of the oligosaccharide at position 330 dramatically decreased expression, precluding further analysis. All other variants were characterized chemically and shown to inhibit C1s activity and C1 activation in the same way as native C1 inhibitor. Likewise, they formed covalent complexes with C1s as shown by SDS-PAGE analysis. C1 inhibitor and its variants inhibited the ability of C1r-like protease to activate C1s, but did not form covalent complexes with this protease. The interaction of C1 inhibitor and its variants with heparin was investigated by surface plasmon resonance, yielding K(D) values of 16.7 x 10(-8) M (C1 inhibitor), 2.3 x 10(-8) M (C1inhDelta97), and 3.6 x 10(-8) M (C1inhDelta97DM). C1s also bound to heparin, with lower affinity (K(D) = 108 x 10(-8) M). Using the same technique, 50% inhibition of the binding of C1 inhibitor and C1s to heparin was achieved using heparin oligomers containing eight and six saccharide units, respectively. These values roughly correlate with the size of 10 saccharide units yielding half-maximal potentiation of the inhibition of C1s activity by C1 inhibitor, consistent with a "sandwich" mechanism. Using a thermal shift assay, heparin was shown to interact with the C1s serine protease domain and the C1 inhibitor serpin domain, increasing and decreasing their thermal stability, respectively. PMID- 20351193 TI - Estradiol suppresses NF-kappa B activation through coordinated regulation of let 7a and miR-125b in primary human macrophages. AB - Previous findings suggest that 17beta-estradiol (estradiol) has a suppressive effect on TNF-alpha, but the mechanism by which estradiol regulates TNF-alpha expression in primary human macrophages is unknown. In this article, we demonstrate that pretreatment of human macrophages with estradiol attenuates LPS induced TNF-alpha expression through the suppression of NF-kappaB activation. Furthermore, we show that activation of macrophages with LPS decreases the expression of kappaB-Ras2, an inhibitor of NF-kappaB signaling. Estradiol pretreatment abrogates this decrease, leading to the enhanced expression of kappaB-Ras2 with LPS stimulation. Additionally, we identified two microRNAs, let 7a and miR-125b, which target the kappaB-Ras2 3' untranslated region (UTR). LPS induces let-7a and inhibits miR-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 3'UTR reporter assays demonstrate that let-7a destabilizes the kappaB-Ras2 3'UTR, whereas miR-125b enhances its stability, resulting in decreased kappaB-Ras2 in response to LPS. Our data suggest that pretreatment with estradiol reverses this effect. We propose a novel mechanism for estradiol inhibition of LPS-induced NF-kappaB signaling in which kappaB-Ras2 expression is induced by estradiol via regulation of let-7a and miR-125b. These findings are significant in that they are the first to demonstrate that estradiol represses NF-kappaB activation through the induction of kappaB-Ras2, a key inhibitor of NF-kappaB signaling. PMID- 20351194 TI - Evidence for a TCR affinity threshold delimiting maximal CD8 T cell function. AB - Protective adaptive immune responses rely on TCR-mediated recognition of Ag derived peptides presented by self-MHC molecules. However, self-Ag (tumor) specific TCRs are often of too low affinity to achieve best functionality. To precisely assess the relationship between TCR-peptide-MHC binding parameters and T cell function, we tested a panel of sequence-optimized HLA-A(*)0201/NY-ESO 1(157-165)-specific TCR variants with affinities lying within physiological boundaries to preserve antigenic specificity and avoid cross-reactivity, as well as two outliers (i.e., a very high- and a low-affinity TCR). Primary human CD8 T cells transduced with these TCRs demonstrated robust correlations between binding measurements of TCR affinity and avidity and the biological response of the T cells, such as TCR cell-surface clustering, intracellular signaling, proliferation, and target cell lysis. Strikingly, above a defined TCR-peptide-MHC affinity threshold (K(D) < approximately 5 muM), T cell function could not be further enhanced, revealing a plateau of maximal T cell function, compatible with the notion that multiple TCRs with slightly different affinities participate equally (codominantly) in immune responses. We propose that rational design of improved self-specific TCRs may not need to be optimized beyond a given affinity threshold to achieve both optimal T cell function and avoidance of the unpredictable risk of cross-reactivity. PMID- 20351195 TI - Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentation. AB - Many MHC class I-binding peptides are generated as N-extended precursors during protein degradation by the proteasome. These peptides can subsequently be trimmed by aminopeptidases in the cytosol and/or the endoplasmic reticulum (ER) to produce mature epitope. However, the contribution and specificity of each of these subcellular compartments in removing N-terminal amino acids for Ag presentation is not well defined. In this study, we investigated this issue for antigenic precursors that are expressed in the cytosol. By systematically varying the N-terminal flanking sequences of peptides, we show that the amino acids upstream of an epitope precursor are a major determinant of the amount of Ag presentation. In many cases, MHC class I-binding peptides are produced through sequential trimming in the cytosol and ER. Trimming of flanking residues in the cytosol contributes most to sequences that are poorly trimmed in the ER. Because N-terminal trimming has different specificity in the cytosol and ER, the cleavage of peptides in both of these compartments serves to broaden the repertoire of sequences that are presented. PMID- 20351198 TI - Distal semitendinosus ruptures in elite-level athletes: low success rates of nonoperative treatment. AB - BACKGROUND: No case series of isolated complete rupture of the distal semitendinosus tendon have been reported previously. PURPOSE: This study was undertaken to increase awareness and report the authors' treatment experience, particularly the less than favorable results of nonoperative initial treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors identified 25 cases of distal semitendinosus tendon rupture over a 14-year period (1991 2005). All players were male professional (20), collegiate (4), or high-level amateur (1) athletes. Follow-up of 17 cases averaged 13 months (range, 4-55), and 8 patients were lost to follow-up. Eight Major League Baseball, 8 National Football League, and 1 National Hockey League athletes were included in this study. Early treatment experience always involved nonoperative treatment, including rest, modalities, and rehabilitation exercises, followed by functional progression. "Recovery" was defined by clinical criteria including clearance to return to play. Failure to improve with nonoperative treatment, and thus requiring surgical treatment, was deemed a failure of nonoperative treatment. There were 12 players who had initial nonoperative treatment. The authors had later experience with 5 players who had surgery early in the acute phase in hopes of speeding return to competition. RESULTS: In the nonoperative treatment group (12), 7 players recovered at an average of 10.4 weeks (range, 3-35). Five of these players (42%) failed initial nonoperative treatment (mean, 16.8 weeks) and subsequently had surgery to resect the torn tendon and surrounding scar tissue. These 5 players recovered at an average of 12.8 weeks postoperatively. In the acute surgery group, 5 players had surgery to resect the torn tendon and scar tissue within 4 weeks of injury. The acute-phase group had an average recovery of 6.8 weeks after surgery. CONCLUSION: Distal semitendinosus ruptures frequently (42%) do not recover after nonoperative treatment. Acute surgical resection of the completely ruptured semitendinosus tendon may speed recovery when the athlete has a tender mass and difficulty extending the knee fully in the stance phase of gate. Future investigation is warranted to compare the long-term outcome of nonoperative treatment with that after acute surgery. PMID- 20351196 TI - Estrogen receptor-related receptor alpha mediates up-regulation of aromatase expression by prostaglandin E2 in prostate stromal cells. AB - Estrogen receptor-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily of transcription factors. ERRalpha is highly expressed in the prostate, especially in prostate stromal cells. However, little is known about the regulation and function of ERRalpha, which may contribute to the progression of prostatic diseases. We previously found that prostaglandin E2 (PGE2) up-regulated the expression of aromatase in prostate stromal cells. Here we show that PGE2 also up-regulates the expression of ERRalpha, which, as a transcription factor, further mediates the regulatory effects of PGE2 on the expression of aromatase. ERRalpha expression was up-regulated by PGE2 in prostate stromal cell line WPMY-1, which was mediated mainly through the protein kinase A signaling pathway by PGE2 receptor EP2. Suppression of ERRalpha activity by chlordane (an antagonist of ERRalpha) or small interfering RNA knockdown of ERRalpha blocked the increase of expression and promoter activity of aromatase induced by PGE2. Overexpression of ERRalpha significantly increased aromatase expression and promoter activity, which were further augmented by PGE2. Chromatin immunoprecipitation assay demonstrated that ERRalpha directly bound to the aromatase promoter in vivo, and PGE2 enhanced the recruitment of ERRalpha and promoted transcriptional regulatory effects on aromatase expression in WPMY-1. 17Beta-estradiol concentration in WPMY-1 medium was up-regulated by ERRalpha expression, and that was further increased by PGE2. Our results provided evidence that ERRalpha contributed to local estrogen production by up-regulating aromatase expression in response to PGE2 and provided further insights into the potential role of ERRalpha in estrogen-related prostatic diseases. PMID- 20351199 TI - Association between mechanical axis of the leg and osteochondritis dissecans of the knee: radiographic study on 103 knees. AB - BACKGROUND: The cause of osteochondritis dissecans (OCD) is unknown, but mechanical factors seem to play a role. PURPOSE: To identify a relationship between localization of OCD and mechanical axis of the leg. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Using bilateral full-leg standing radiographs, we analyzed the position of the mechanical axis of the leg in a group of 93 adolescent and adult patients (103 knees) with OCD of the medial or lateral femoral condyle. RESULTS: The location of OCD and the position of the mechanical axis in the same knee compartment was significantly correlated for both knees with medial (P < .001) as well as lateral (P < .012) compartment OCD. In the medial OCD group, the mean mechanical axis was located in the medial knee compartment (28% medial +/- 2.8%; range, 100% medial to 14% lateral) with a statistically insignificant medial shift with respect to the unaffected side. In lateral OCD, the mean mechanical axis was located laterally (13% lateral +/- 3.9%; range, 13% medial to 60% lateral) with a significant shift from the medial into the lateral knee compartment when comparing unaffected with affected knees. No significant difference was observed between adolescents with open growth plates compared with adults with closed growth plates (P > .05). CONCLUSION: We found an association between medial condyle OCD and varus axis and between lateral condyle OCD and valgus axis. This evokes higher loading of the affected than of the unaffected knee compartment, and therefore, axial alignment may be a cofactor in OCD of the femoral condyles. PMID- 20351197 TI - Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. AB - Although rapid, membrane-activated estrogen receptor (ER) signaling is no longer controversial, the biological function of this nongenomic signaling is not fully characterized. We found that rapid signaling from membrane-associated ER regulates the histone methyltransferase enhancer of Zeste homolog 2 (EZH2). In response to both 17beta-estradiol (E2) and the xenoestrogen diethylstilbestrol, ER signaling via phosphatidylinositol 3-kinase/protein kinase B phosphorylates EZH2 at S21, reducing levels of trimethylation of lysine 27 on histone H3 in hormone-responsive cells. During windows of uterine development that are susceptible to developmental reprogramming, activation of this ER signaling pathway by diethylstilbestrol resulted in phosphorylation of EZH2 and reduced levels of trimethylation of lysine 27 on histone H3 in chromatin of the developing uterus. Furthermore, activation of nongenomic signaling reprogrammed the expression profile of estrogen-responsive genes in uterine myometrial cells, suggesting this as a potential mechanism for developmental reprogramming caused by early-life exposure to xenoestrogens. These data demonstrate that rapid ER signaling provides a direct linkage between xenoestrogen-induced nuclear hormone receptor signaling and modulation of the epigenetic machinery during tissue development. PMID- 20351200 TI - Tendon disorders of the foot and ankle, part 3: the posterior tibial tendon. AB - This article provides a review of posterior tibial tendon pathology and the authors' preferred management. The tibialis posterior musculotendinous unit is the most powerful inverter of the foot and an important dynamic stabilizer of the arch. In the stance phase of the gait cycle, it serves as an initiator of both ankle plantar flexion and subtalar inversion. This creates a rigid midfoot by stabilizing the transverse tarsal joint, and allows for increased power generation by the gastrocsoleus complex through toe-off. Injuries to the posterior tibialis tendon include traumatic laceration and dislocation, as well as tenosynovitis and tendinopathy, which can lead to attenuation and rupture. If these injuries are not addressed, significant clinical deformity and disability can result. PMID- 20351201 TI - IKDC or KOOS: which one captures symptoms and disabilities most important to patients who have undergone initial anterior cruciate ligament reconstruction? AB - BACKGROUND: Knee-specific patient-reported outcome measures are frequently used after anterior cruciate ligament reconstruction but little is known about whether they measure outcomes important to patients. PURPOSE: The aim of this study was to identify which instrument, the Knee injury and Osteoarthritis Outcome Score (KOOS) or the International Knee Documentation Committee Subjective Knee Form (IKDC), captures symptoms and disabilities most important to patients who have undergone initial anterior cruciate ligament reconstruction. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: Data were collected from 126 participants of an Internet knee forum. A self-reported online questionnaire was developed consisting of demographic and surgical data, the Tegner Activity Scale, and 49 consolidated items from the KOOS and the IKDC. Item importance, frequency, and frequency-importance product were calculated. RESULTS: Seventy-eight percent of the items from the IKDC were experienced by more than half of the patients, compared with 57% from the KOOS. Items extracted from the Function in Sports/Recreation and Quality of Life KOOS subscales were highly important to this group of patients. For patients 12 months or more after anterior cruciate ligament reconstruction, 94% of the IKDC items had a frequency-importance product of 1 or less compared with 86% of the KOOS items. CONCLUSION: Overall, the IKDC items outperformed the KOOS items on all of the 5 criteria with the exception of the frequency-importance product for patients who were 12 months after anterior cruciate ligament reconstruction. The KOOS Function in Sports/Recreation and Knee Related Quality of Life subscales outperformed the IKDC for the total cohort as well as for male and female subgroups. However, differences in individual items were not always evident from either total scale or subscale ratings. Studies should use patient-reported outcomes that reflect patients' most important concerns and further prospective longitudinal research is required in this area. PMID- 20351202 TI - Biomechanical comparison of a modified Weaver-Dunn and a free-tissue graft reconstruction of the acromioclavicular joint complex. AB - BACKGROUND: Most surgical reconstructions of the separated acromioclavicular joint do not address the injured ligaments and capsule of the acromioclavicular joint. PURPOSE: This study was undertaken to compare the biomechanical characteristics of a modified Weaver-Dunn reconstruction and an intramedullary acromioclavicular joint reconstruction that uses a free-tissue graft for reconstruction of both the coracoclavicular and acromioclavicular ligaments. STUDY DESIGN: Controlled laboratory study. METHODS: Each pair of 6 matched pairs of cadaveric shoulders was randomly selected for a modified Weaver-Dunn reconstruction on 1 side and the contralateral side was used for free-tissue graft reconstruction of the coracoclavicular and acromioclavicular ligamentous complexes. Anterior-posterior and superior-inferior acromioclavicular joint translation (in millimeters) was measured with acromioclavicular joint compressions of 10, 20, and 30 N, and with translational loads of 10 and 15 N both before and after acromioclavicular joint reconstruction. Load-to-failure testing was then performed for each construct. Repeated-measures analysis of variance (translational testing) and Wilcoxon signed rank test (load-to-failure testing), both with P = .05, were used for statistical analysis. RESULTS: Mean anterior-posterior and superior-inferior translation of the intramedullary acromioclavicular joint reconstruction was significantly less than that of the modified Weaver-Dunn under all loading conditions (P < .001 and P = .001, respectively), but was not significantly different from that of the intact state (P = .656 and P = .173, respectively). Although the mean ultimate and yield loads and linear stiffness for the intramedullary acromioclavicular reconstruction were greater than that of the modified Weaver-Dunn reconstruction, this did not reach statistical significance (P = .625, P = .625, and P = .625, respectively). CONCLUSION: Acromioclavicular joint reconstruction with free-tissue graft for both the coracoclavicular and acromioclavicular ligamentous complexes demonstrates initial stability significantly better than a modified Weaver-Dunn and similar to that of intact specimens. CLINICAL RELEVANCE: This acromioclavicular joint reconstruction provides the surgeon with a relatively nondestructive option. PMID- 20351203 TI - Clinical follow-up of professional baseball players undergoing ulnar collateral ligament reconstruction using the new Kerlan-Jobe Orthopaedic Clinic overhead athlete shoulder and elbow score (KJOC Score). AB - BACKGROUND: There are no validated outcome measures consistently used in the literature to report results of ulnar collateral ligament reconstruction in overhead athletes. HYPOTHESIS: The Kerlan-Jobe Orthopaedic Clinic Overhead Athlete Shoulder and Elbow score (KJOC score) will correlate with other validated scores for upper extremity assessment but will be more accurate in evaluating ulnar collateral ligament reconstruction outcomes in professional baseball players. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Fifty-five professional baseball players who underwent ulnar collateral ligament reconstruction were asked to complete the KJOC score, the Disabilities of the Arm, Shoulder and Hand (DASH) score, and the DASH sports module. Players were separated into 3 categories-(1) playing without pain, (2) playing with pain, and (3) not playing because of pain-and compared with 123 asymptomatic throwers. Pearson (parametric) and Spearman rank (nonparametric) correlations among the 3 systems were conducted to validate the KJOC score. Means across categories were compared using a Wilcoxon rank-sum test, and a threshold score separating categories 1 and 3 was determined using receiver operator characteristic discrimination analysis. RESULTS: Significant correlations were found between the KJOC score and the DASH (-.693, P < .0001), and the DASH sports module (-0.804, P < .0001). Only the KJOC score was able to discriminate between categories 2 and 3, as well as category 1 and the uninjured population. In addition, the KJOC score was the most sensitive and accurate method of discriminating category 1 from category 3, with a threshold score of 81.3. CONCLUSION: The results of this study validate the use of the KJOC score for evaluation of overhead athletes undergoing ulnar collateral ligament reconstruction. The KJOC score is the most sensitive score for detecting subtle changes in performance in the throwing athlete. PMID- 20351204 TI - Molecular epidemiology of Mycobacterium leprae as determined by structure neighbor clustering. AB - It has proven challenging to investigate the molecular epidemiology of Mycobacterium leprae, the causative agent of leprosy, due to difficulties with culturing of the organism and a lack of genetic heterogeneity between strains. Recently, a cost-effective panel of variable-number tandem-repeat (VNTR) markers has been developed. Use of this panel allows some of those limitations to be overcome and has allowed the genotyping of 475 M. leprae strains from six different countries. In the present report, we provide a comprehensive analysis of the relationships among the strains in order to investigate the patterns of transmission and migration of M. leprae. We find phylogenetic analysis to be inadequate and have developed an alternative method, structure-neighbor clustering, which assigns isolates with the most similar genotypes to the same groups and, subsequently, subgroups, without inferring how the strains descended from a common ancestor. We validate the approach by using simulated data and detecting expected epidemiological relationships from experimental data. Our results suggest that most M. leprae strains from a given country cluster together and that the occasional isolates assigned to different clusters are a consequence of migration. We found three genetically distinguishable populations among isolates from the Philippines, as well as evidence for the significant influx of strains to that nation from India. We also report that reference strain TN originated from the Philippines and not from India, as was previously believed. Lastly, analysis of isolates from the same families and villages suggests that most community infections originate from a common source or person-to-person transmission but that infection from independent sources does occur with measurable frequency. PMID- 20351205 TI - High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa. AB - Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections. PMID- 20351206 TI - Establishment of a novel quantitative hepatitis D virus (HDV) RNA assay using the Cobas TaqMan platform to study HDV RNA kinetics. AB - Determination of hepatitis D virus (HDV) viremia represents the "gold standard" for the diagnosis of HDV infection. Hepatitis B virus (HBV)-HDV coinfection frequently leads to end-stage liver disease and hepatocellular carcinoma. No commercial assay for HDV RNA quantification that includes automated nucleic acid extraction is available, and in-house PCR tests are not well standardized. However, knowledge of HDV RNA levels may give important information for patient management and could be a useful tool for monitoring the response to antiviral therapies. One platform that is widely used for HBV DNA or HCV RNA quantification is the Cobas Ampliprep/TaqMan system. Using the utility channel of this platform, we established a novel protocol for TaqMan-based HDV RNA quantification after automatic extraction of RNA by the Ampliprep system. The assay was specific and showed linearity over a wide range from 3 x 10(2) to 10(7) copies/ml. Reproducibility was demonstrated by determination of the interrun and intrarun variabilities, which were similar to those achieved with the commercially available Cobas TaqMan assays for HCV RNA and HBV DNA. HDV RNA levels were stable in whole blood (n = 4), plasma (n = 3), and serum (n = 3) samples at room temperature for up to 6 days. Importantly, HDV RNA viremia showed only minor fluctuations, with the log(10) coefficient of variation being between 1.3 and 11.2% for hepatitis delta patients studied every 2 weeks for up to 3 months (n = 6), while a rapid viral decline was observed early during treatment with pegylated alfa-2a interferon (n = 6). In conclusion, this novel automated HDV RNA assay is a useful tool for monitoring HDV-infected patients both before and during antiviral therapy. PMID- 20351207 TI - Development and evaluation of loop-mediated isothermal amplification assay for rapid and inexpensive detection of cytomegalovirus DNA in vitreous specimens from suspected cases of viral retinitis. AB - A loop-mediated isothermal amplification (LAMP) assay for the rapid detection of cytomegalovirus (CMV) was developed and evaluated. The LAMP assay specifically amplified only CMV DNA, and no cross-reactivity with the DNA of herpes simplex virus type 1, varicella-zoster virus, adenovirus, Aspergillus flavus, or Staphylococcus aureus was observed. The sequences of the LAMP assay-positive CMV products were perfectly (100%) matched with the CMV sequence deposited in the GenBank database. The sensitivity of the LAMP assay was found to be 10 copies/microl of CMV DNA. Vitreous samples from 40 patients with suspected retinitis were subjected to LAMP and real-time PCR for the detection of CMV. Of 40 patients with suspected viral retinitis, 10 tested positive for CMV by the real-time PCR and LAMP assays. A 100% concordance was observed between the results of the two methods. The LAMP assay is a rapid, highly specific, and sensitive method for the diagnosis of retinitis caused by CMV. PMID- 20351208 TI - Influence of media and testing methodology on susceptibility to tigecycline of Enterobacteriaceae with reported high tigecycline MIC. AB - The tigecycline susceptibility of six different Enterobacteriaceae strains with reported high tigecycline MICs was determined in quintuplicate by four methodologies using Mueller-Hinton agar and broth from six manufacturers. The MICs determined by Etest were a >or=1-fold dilution lower than those determined by broth microdilution and agar dilution, with the highest modal values given by agar dilution. The highest modal MICs were obtained using Oxoid medium, and the lowest inhibition zone values (disc diffusion) were obtained using Oxoid and bioMerieux media. The lowest MICs were obtained by Etest using Difco or Merck media. PMID- 20351209 TI - Development of a DNA microarray for detection and serotyping of enterotoxigenic Escherichia coli. AB - Enterotoxigenic Escherichia coli (ETEC) is a common pathogen worldwide causing infectious diarrhea, especially traveler's diarrhea. Traditional physiological assays, immunoassays, and PCR-based methods for the detection of ETEC target the heat-labile enterotoxin and/or the heat-stable enterotoxin. Separate serotyping methods using antisera are required to determine the ETEC serogroup. In this study, we developed a DNA microarray that can simultaneously detect enterotoxin genes and the 19 most common O serogroup genes in ETEC strains. The specificity and reproducibility of this approach were verified by hybridization to 223 strains: 50 target reference or clinical strains and 173 other strains, including those belonging to other E. coli O serogroups and closely related species. The sensitivity of detection was determined to be 50 ng of genomic DNA or 10(8) CFU per ml of organisms in pure culture. The random PCR strategy used in this study with minimal bias provides an effective alternative to multiplex PCR for the detection of pathogens using DNA microarrays. The assay holds promise for applications in the clinical diagnosis and epidemiological surveillance of pathogenic microorganisms. PMID- 20351210 TI - Improved detection of Lassa virus by reverse transcription-PCR targeting the 5' region of S RNA. AB - The method of choice for the detection of Lassa virus is reverse transcription (RT)-PCR. However, the high degree of genetic variability of the virus poses a problem with the design of RT-PCR assays that will reliably detect all strains. Recently, we encountered difficulties in detecting some strains from Liberia and Nigeria in a commonly used glycoprotein precursor (GPC) gene-specific RT-PCR assay (A. H. Demby, J. Chamberlain, D. W. Brown, and C. S. Clegg, J. Clin. Microbiol. 32:2898-2903, 1994), which prompted us to revise the protocol. The design of the new assay, the GPC RT-PCR/2007 assay, took into account 62 S RNA sequences from all countries where Lassa fever is endemic, including 40 sequences generated from the strains in our collection. The analytical sensitivity of the new assay was determined with 11 strains from Sierra Leone, Liberia, Ivory Coast, and Nigeria by probit analysis; the viral loads detectable with a probability of 95% ranged from 342 to 2,560 S RNA copies/ml serum, which corresponds to 4 to 30 S RNA copies/assay. The GPC RT-PCR/2007 assay was validated with 77 serum samples and 1 cerebrospinal fluid sample from patients with laboratory-confirmed Lassa fever. The samples mainly originated from Liberia and Nigeria and included strains difficult to detect in the assay of 1994. The GPC RT-PCR/2007 assay detected virus in all clinical specimens (100% sensitivity). In conclusion, a new RT-PCR assay, based in part on the protocol developed by Demby et al. in 1994, for the detection of Lassa virus is described. Compared to the assay developed in 1994, the GPC RT-PCR/2007 assay offers improved sensitivity for the detection of Liberian and Nigerian Lassa virus strains. PMID- 20351211 TI - Rubella virus genotypes in the People's Republic of China between 1979 and 2007: a shift in endemic viruses during the 2001 Rubella Epidemic. AB - The incidence of rubella cases in China from 1991 to 2007 was reviewed, and the nucleotide sequences from 123 rubella viruses collected during 1999 to 2007 and 4 viral sequences previously reported from 1979 to 1984 were phylogenetically analyzed. Rubella vaccination was not included in national immunization programs in China before 2007. Changes in endemic viruses were compared with incidences of rubella epidemics. The results showed that rubella epidemics occur approximately every 6 to 8 years (1993/1994, 2001, and 2007), and a shift of disease burden to susceptible young adults was observed. The Chinese rubella virus sequences were categorized into 5 of the 13 rubella virus genotypes, 1a, 1E, 1F, 2A, and 2B; cocirculations of these different genotypes were found in China. In Anhui province, a shift in the predominant genotype from 1F and 2B to 1E coincided with the 2001 rubella epidemic. This shift may have occurred throughout China during 2001 to 2007. This study investigated the genotype distribution of rubella viruses in China over a 28-year period to establish an important genetic baseline in China during its prevaccination era. PMID- 20351212 TI - Molecular characterization of methicillin-resistant Staphylococcus aureus with emergence of epidemic clones of sequence type (ST) 22 and ST 772 in Mumbai, India. AB - A total of 412 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated between October 2006 and June 2009, representing a mixed hospital- and community-associated patient population from Mumbai, India, were evaluated. MRSA was characterized by multiplex PCR amplification of the Panton-Valentine leukocidin (PVL) gene and the mecA gene, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing (MLST). PCR results were compared with patient risk factors (CDC guidelines) and antimicrobial susceptibility profiles. A total of 395 MRSA strains were mecA positive, and 224 were PVL gene positive. A total of 97 mecA-positive strains were SCCmec III (25%), 136 were SCCmec IV (34%), and 162 were SCCmec V (41%). All SCCmec III strains were multidrug resistant, and all patients had risk factors. Of the SCCmec IV and V strains, 73% were multidrug susceptible and 72% of the associated patients had no risk factors. The multidrug susceptibility and absence of patient risk factors in 72% of cases with SCCmec IV and SCCmec V MRSA demonstrate the presence of community-associated MRSA (CA-MRSA) in Mumbai. Twenty-one percent of these patients had risk factors, signifying CA-MRSA infiltration into hospitals. MLST showed clonal expansion of multidrug-susceptible sequence type (ST) 22 (SCCmec IV) and ST 772 (SCCmec V), both of which feature in Asian studies and may be slowly replacing the multidrug-resistant ST 239 (SCCmec III) in hospitals. The PVL gene-positive methicillin-sensitive S. aureus (MSSA) strains were ST 30 and were postulated to be related to the penicillin-resistant S. aureus phage type 80/81, notorious for its virulence in the 1950s. PMID- 20351213 TI - Bacterial rRNA-targeted reverse transcription-PCR used to identify pathogens responsible for fever with neutropenia. AB - The purpose of this study was to evaluate the clinical utility of bacterial rRNA targeted reverse transcription-quantitative PCR (BrRNA RT-qPCR) assays for identifying the bacterial pathogens that cause fever with neutropenia in pediatric cancer patients, by comparing the bacterial detection rate of this technique with that of blood culture. One milliliter of blood was collected from pediatric patients who developed fever with neutropenia following cancer chemotherapy. BrRNA RT-qPCR was performed using 16 primer sets, each designed for a specific type of bacteria. The entire BrRNA RT-qPCR procedure took less than 5 h. Blood culture was performed at the same time, following the standard institutional procedure. Blood from 13 patients was collected during 23 febrile neutropenic episodes. Of these samples, bacteria were identified in 16 by BrRNA RT-qPCR (69.6%) and in 4 by blood culture (17.4%, P<0.001). In all 4 blood culture-positive samples, BrRNA RT-qPCR detected the same type of bacteria as that identified by culture. In 9 samples, more than 4 types of bacteria were identified simultaneously by BrRNA RT-qPCR, most of which were anaerobic bacteria known to be part of the gut flora. We conclude that BrRNA RT-qPCR could be useful in the diagnosis of fever with neutropenia, given its high bacterial detection rate, short turnaround time, and the small blood sample required compared with the standard blood culture techniques. Our findings also indicate that anaerobic intestinal bacteria, which are difficult to detect by standard culture techniques, may be responsible for some cases of febrile neutropenia. PMID- 20351214 TI - Characterization of three Staphylococcus aureus isolates from a 17-year-old female who died of tampon-related toxic shock syndrome. AB - We report the identification and characterization of three Staphylococcus aureus isolates recovered from throat and vaginal cultures, as well as from an axillary abscess, of a 17-year-old female who died of tampon-related toxic shock syndrome. The three S. aureus isolates were unrelated as determined by pulsed-field gel electrophoresis. The vaginal isolate was mecA, Panton-Valentine leukocidin, and staphylococcal enterotoxin B and C negative, toxic shock syndrome toxin 1 positive, and staphylococcal cassette chromosome mec element (SCCmec) untypeable, which was consistent with the clinical and autopsy findings that death was due to tampon-related toxic shock syndrome. PMID- 20351215 TI - New automated hepatitis C virus (HCV) core antigen assay as an alternative to real-time PCR for HCV RNA quantification. AB - An automated hepatitis C virus (HCV) antigen (Ag) assay was evaluated with clinical samples. Determination of HCV Ag and RNA levels in 282 subjects using Abbott HCV Ag and Roche Cobas TaqMan assays revealed that these two tests were highly correlated (r = 0.9464). Thus, the HCV Ag assay could be an alternative test to quantitative reverse transcription-PCR. PMID- 20351216 TI - Critical determinants for chromatin binding by Saccharomyces cerevisiae Yng1 exist outside of the plant homeodomain finger. AB - The temporal and spatial regulation of histone post-translational modifications is essential for proper chromatin structure and function. The Saccharomyces cerevisiae NuA3 histone acetyltransferase complex modifies the amino-terminal tail of histone H3, but how NuA3 is targeted to specific regions of the genome is not fully understood. Yng1, a subunit of NuA3 and a member of the Inhibitor of Growth (ING) protein family, is required for the interaction of NuA3 with chromatin. This protein contains a C-terminal plant homeodomain (PHD) finger that specifically interacts with lysine 4-trimethylated histone H3 (H3K4me3) in vitro. This initially suggested that NuA3 is targeted to regions bearing the H3K4me3 mark; however, deletion of the Yng1 PHD finger does not disrupt the interaction of NuA3 with chromatin or result in a phenotype consistent with loss of NuA3 function in vivo. In this study, we uncovered the molecular basis for the discrepancies in these data. We present both genetic and biochemical evidence that full-length Yng1 has two independent histone-binding motifs: an amino terminal motif that binds unmodified H3 tails and a carboxyl-terminal PHD finger that specifically recognizes H3K4me3. Although these motifs can bind histones independently, together they increase the apparent association of Yng1 for the H3 tail. PMID- 20351217 TI - Degradation of the Saccharomyces cerevisiae mating-type regulator alpha1: genetic dissection of cis-determinants and trans-acting pathways. AB - Mating phenotype in the yeast Saccharomyces cerevisiae is a dynamic trait, and efficient transitions between alternate haploid cell types allow the organism to access the advantageous diploid form. Mating identity is determined by cell type specific transcriptional regulators, but these factors must be rapidly removed upon mating-type switching to allow the master regulators of the alternate state to establish a new gene expression program. Targeted proteolysis by the ubiquitin proteasome system is a commonly employed strategy to quickly disassemble regulatory networks, and yeast use this approach to evoke efficient switching from the alpha to the a phenotype by ensuring the rapid removal of the alpha2 transcriptional repressor. Transition to the a cell phenotype, however, also requires the inactivation of the alpha1 transcriptional activator, but the mechanism by which this occurs is currently unknown. Here, we report a central role for the ubiquitin-proteasome system in alpha1 inactivation. The alpha1 protein is constitutively short lived and targeted for rapid turnover by multiple ubiquitin-conjugation pathways. Intriguingly, the alpha-domain, a conserved region of unknown function, acts as a degradation signal for a pathway defined by the SUMO-targeted ligase Slx5-Slx8, which has also been implicated in the rapid destruction of alpha2. Our observations suggest coordinate regulation in the turnover of two master regulatory transcription factors ensures a rapid mating type switch. PMID- 20351218 TI - Bayesian inference of genetic parameters based on conditional decompositions of multivariate normal distributions. AB - It is widely recognized that the mixed linear model is an important tool for parameter estimation in the analysis of complex pedigrees, which includes both pedigree and genomic information, and where mutually dependent genetic factors are often assumed to follow multivariate normal distributions of high dimension. We have developed a Bayesian statistical method based on the decomposition of the multivariate normal prior distribution into products of conditional univariate distributions. This procedure permits computationally demanding genetic evaluations of complex pedigrees, within the user-friendly computer package WinBUGS. To demonstrate and evaluate the flexibility of the method, we analyzed two example pedigrees: a large noninbred pedigree of Scots pine (Pinus sylvestris L.) that includes additive and dominance polygenic relationships and a simulated pedigree where genomic relationships have been calculated on the basis of a dense marker map. The analysis showed that our method was fast and provided accurate estimates and that it should therefore be a helpful tool for estimating genetic parameters of complex pedigrees quickly and reliably. PMID- 20351220 TI - Searching for recursive causal structures in multivariate quantitative genetics mixed models. AB - Biology is characterized by complex interactions between phenotypes, such as recursive and simultaneous relationships between substrates and enzymes in biochemical systems. Structural equation models (SEMs) can be used to study such relationships in multivariate analyses, e.g., with multiple traits in a quantitative genetics context. Nonetheless, the number of different recursive causal structures that can be used for fitting a SEM to multivariate data can be huge, even when only a few traits are considered. In recent applications of SEMs in mixed-model quantitative genetics settings, causal structures were preselected on the basis of prior biological knowledge alone. Therefore, the wide range of possible causal structures has not been properly explored. Alternatively, causal structure spaces can be explored using algorithms that, using data-driven evidence, can search for structures that are compatible with the joint distribution of the variables under study. However, the search cannot be performed directly on the joint distribution of the phenotypes as it is possibly confounded by genetic covariance among traits. In this article we propose to search for recursive causal structures among phenotypes using the inductive causation (IC) algorithm after adjusting the data for genetic effects. A standard multiple-trait model is fitted using Bayesian methods to obtain a posterior covariance matrix of phenotypes conditional to unobservable additive genetic effects, which is then used as input for the IC algorithm. As an illustrative example, the proposed methodology was applied to simulated data related to multiple traits measured on a set of inbred lines. PMID- 20351219 TI - The Drosophila planar polarity proteins inturned and multiple wing hairs interact physically and function together. AB - The conserved frizzled (fz) pathway regulates planar cell polarity in both vertebrate and invertebrate animals. This pathway has been most intensively studied in the wing of Drosophila, where the proteins encoded by pathway genes all accumulate asymmetrically. Upstream members of the pathway accumulate on the proximal, distal, or both cell edges in the vicinity of the adherens junction. More downstream components including Inturned and Multiple Wing Hairs accumulate on the proximal side of wing cells prior to hair initiation. The Mwh protein differs from other members of the pathway in also accumulating in growing hairs. Here we show that the two Mwh accumulation patterns are under different genetic control with the early proximal accumulation being regulated by the fz pathway and the latter hair accumulation being largely independent of the pathway. We also establish recruitment by proximally localized Inturned to be a putative mechanism for the localization of Mwh to the proximal side of wing cells. Genetically inturned (in) acts upstream of mwh (mwh) and is required for the proximal localization of Mwh. We show that Mwh can bind to and co immunoprecipitate with Inturned. We also show that these two proteins can function in close juxtaposition in vivo. An InMwh fusion protein provided complete rescue activity for both in and mwh mutations. The fusion protein localized to the proximal side of wing cells prior to hair formation and in growing hairs as expected if protein localization is a key for the function of these proteins. PMID- 20351221 TI - Cardiovascular disease in diabetes. PMID- 20351222 TI - Association of lower plasma fetuin-a levels with peripheral arterial disease in type 2 diabetes: response to Eraso et al. PMID- 20351224 TI - Correction to the 2010 report on the diagnosis and classification of diabetes. PMID- 20351225 TI - Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes: response to Yamamoto et al. PMID- 20351227 TI - Review of adverse events associated with false glucose readings measured by GDH PQQ-based glucose test strips in the presence of interfering sugars. AB - OBJECTIVE: To assess the implications of falsely elevated glucose readings measured with glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) test strips. RESEARCH DESIGN AND METHODS: We conducted a review of the Food and Drug Administration's Manufacturer and User Facility Device Experience database and medical literature for adverse events (AEs) associated with falsely elevated glucose readings with GDH-PQQ test strips in the presence of interfering sugars. RESULTS: Eighty-two reports were identified: 16 (20%) were associated with death, 46 (56%) with severe hypoglycemia, and 12 (15%) with nonsevere hypoglycemia. In eight reports (10%), the AE was not described. Forty-two events (51%) occurred in the U.S. Although most events occurred in hospitalized patients, at least 14 (17%) occurred in outpatients. Agents most commonly associated with AEs were icodextrin-containing peritoneal dialysate and maltose-containing intravenous immune globulin. CONCLUSIONS: GDH-PQQ test strips pose a safety risk to insulin using patients treated with agents containing or metabolized to interfering sugars. PMID- 20351228 TI - Identifying psychosocial interventions that improve both physical and mental health in patients with diabetes: a systematic review and meta-analysis. AB - OBJECTIVE: Patients with diabetes suffer high rates of mental health problems, and this combination is associated with poor outcomes. Although effective treatments exist for both diabetes and mental health problems, delivering services for physical and mental health problems separately ignores their interaction and may be inefficient. This systematic review sought to identify psychosocial interventions that could improve both the physical and mental health of patients with diabetes. RESEARCH DESIGN AND METHODS: Studies were identified from the following databases: CENTRAL, MEDLINE, Excerpta Medica (EMBASE), Psychinfo, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The review included randomized controlled trials in patients with type 1 and type 2 diabetes who received psychosocial interventions and where both mental health and physical health outcomes were reported. Data were extracted on study quality, the content and process of interventions, and outcomes. RESULTS: Eighty-five eligible comparisons were identified, of which 49 reported sufficient data for analysis. Psychosocial interventions modestly improved A1C (standardized mean difference -0.29 [95% CI -0.37 to -0.21]) and mental health outcomes (-0.16 [ 0.25 to -0.07]). However, there was a limited association between the effects on A1C and mental health, and no intervention characteristics predicted benefit on both outcomes. CONCLUSIONS: Managing physical and mental health in long-term conditions are increasingly important. The review did not identify types of interventions that consistently provide benefits for both physical and mental health. Developing such interventions remains an important challenge. The findings have implications for understanding the interaction between physical and mental health problems and for the coordination of care. PMID- 20351229 TI - Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis. AB - OBJECTIVE: Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers. RESULTS: Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]). CONCLUSIONS: Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality. PMID- 20351230 TI - Health systems, patients factors, and quality of care for diabetes: a synthesis of findings from the TRIAD study. PMID- 20351231 TI - Finger-stick glucose monitoring: issues of accuracy and specificity. PMID- 20351232 TI - ACCF/AHA 2010 Position Statement on Composite Measures for Healthcare Performance Assessment: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures (Writing Committee to develop a position statement on composite measures). PMID- 20351233 TI - Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. AB - BACKGROUND: Predicting the risk of recurrent venous thromboembolism (VTE) in an individual patient is often not feasible. We aimed to develop a simple risk assessment model that improves prediction of the recurrence risk. METHODS AND RESULTS: In a prospective cohort study, 929 patients with a first unprovoked VTE were followed up for a median of 43.3 months after discontinuation of anticoagulation. We excluded patients with a strong thrombophilic defect such as a natural inhibitor deficiency, the lupus anticoagulant, and homozygous or combined defects. A total of 176 patients (18.9%) had recurrent VTE. Preselected clinical and laboratory variables (age, sex, location of VTE, body mass index, factor V Leiden, prothrombin G20210A mutation, D-dimer, and in vitro thrombin generation) were analyzed in a Cox proportional hazards model, and those variables that were significantly associated with recurrence were used to compute risk scores. Male sex (hazard ratio versus female sex 1.90, 95% confidence interval 1.31 to 2.75), proximal deep vein thrombosis (hazard ratio versus distal 2.08, 95% confidence interval 1.16 to 3.74), pulmonary embolism (hazard ratio versus distal thrombosis 2.60, 95% confidence interval 1.49 to 4.53), and elevated levels of D-dimer (hazard ratio per doubling 1.27, 95% confidence interval 1.08 to 1.51) were related to a higher recurrence risk. Using these variables, we developed a nomogram that can be used to calculate risk scores and to estimate the cumulative probability of recurrence in an individual patient. The model was cross validated, and patients were assigned to different risk categories based on their risk score. Recurrence rates corresponded well with the different risk categories. CONCLUSIONS: By use of a simple scoring system, the assessment of the recurrence risk in patients with a first unprovoked VTE and without strong thrombophilic defects can be improved. PMID- 20351234 TI - Overexpression of urokinase by plaque macrophages causes histological features of plaque rupture and increases vascular matrix metalloproteinase activity in aged apolipoprotein e-null mice. AB - BACKGROUND: The mechanisms of atherosclerotic plaque rupture are poorly understood. Urokinase-type plasminogen activator (uPA) is expressed at elevated levels by macrophages in advanced human plaques. Patients with evidence of increased plasminogen activation have an elevated risk of major cardiovascular events. We used atherosclerotic mice to test the hypothesis that increased macrophage uPA expression in advanced plaques would cause histological features similar to those in ruptured human plaques. METHODS AND RESULTS: Bone marrow from transgenic mice with increased macrophage uPA expression or nontransgenic controls (all apolipoprotein E-null [Apoe(-/-)]) was transplanted into 35-week old Apoe(-/-) recipients, and innominate lesions and aortas were examined 8 to 13 weeks later. Donor macrophages accumulated in innominate lesions adjacent to plaque caps and in aortas, increasing uPA expression at both sites. Recipients of uPA-overexpressing macrophages had an increased prevalence of intraplaque hemorrhage (61% versus 13%; P=0.002) as well as increased lesion fibrin staining and fibrous cap disruption (P=0.06 for both). Transplantation of uPA overexpressing macrophages increased aortic matrix metalloproteinase activity (40%; P=0.02). This increase was independent of matrix metalloproteinase-9. CONCLUSIONS: In advanced plaques of Apoe(-/-) mice, macrophage uPA overexpression causes intraplaque hemorrhage and fibrous cap disruption, features associated with human plaque rupture. uPA overexpression also increases vascular matrix metalloproteinase activity. These data provide a mechanism that connects macrophage uPA expression, matrix metalloproteinase activity, and plaque rupture features in mice. The data also suggest that elevated plaque plasminogen activator expression and plasminogen activation in humans may be causally linked to plaque rupture and cardiovascular events. PMID- 20351235 TI - Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. AB - BACKGROUND: Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na(+) ([Na(+)](i)) reduces mitochondrial Ca(2+) ([Ca(2+)](m)) by accelerating Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca(2+)](m), we speculated that in failing myocytes, elevated [Na(+)](i) promotes oxidative stress. METHODS AND RESULTS: We used a patch-clamp-based approach to simultaneously monitor cytosolic and mitochondrial Ca(2+) and, alternatively, mitochondrial H(2)O(2) together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by beta-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when [Ca(2+)](m) increased. The transient oxidation of NAD(P)H was closely associated with an increase in mitochondrial H(2)O(2) formation. This reactive oxygen species formation was potentiated when mitochondrial Ca(2+) uptake was blocked (by Ru360) or Ca(2+) efflux was accelerated (by elevation of [Na(+)](i)). In failing myocytes, H(2)O(2) formation was increased, which was prevented by reducing mitochondrial Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. CONCLUSIONS: Besides matching energy supply and demand, mitochondrial Ca(2+) uptake critically regulates mitochondrial reactive oxygen species production. In heart failure, elevated [Na(+)](i) promotes reactive oxygen species formation by reducing mitochondrial Ca(2+) uptake. This novel mechanism, by which defects in ion homeostasis induce oxidative stress, represents a potential drug target to reduce reactive oxygen species production in the failing heart. PMID- 20351236 TI - Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study. AB - BACKGROUND: Coronary artery disease (CAD) is a significant cause of morbidity and mortality in stroke patients. Some patients with asymptomatic CAD might benefit from specific prevention, but the prevalence of asymptomatic CAD is not well known. We assessed the prevalence of >or=50% asymptomatic CAD in patients with ischemic stroke or transient ischemic attack and whether the prevalence is related to traditional vascular risk factors and cervicocephalic atherosclerosis. METHODS AND RESULTS: From January 2006 to February 2009, consecutive patients between 45 and 75 years of age with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack and no prior history of CAD were enrolled in the study. All patients had a 64-section computed tomography coronary angiography and a detailed cervicocephalic arterial workup. Risk factors were assessed individually and through the Framingham Risk Score. Among 300 patients included in the study, 274 had computed tomography coronary angiography. The prevalence of >or=50% asymptomatic CAD was 18% (95% confidence interval [CI], 14 to 23; n=50). Asymptomatic CAD was independently associated with traditional risk factors assessed individually and through the Framingham Risk Score (odds ratio [OR], 2.6; 95% CI, 1.0 to 7.6 for a 10-year risk of coronary heart disease of 10% to 19%; and OR, 7.3; 95% CI, 2.8 to 19.1 for a 10 year-risk of coronary heart disease >or=20%), the presence of at least 1 >or=50% cervicocephalic artery stenosis (OR, 4.0; 95% CI, 1.4 to 11.2), excessive alcohol consumption (OR, 3.1; 95% CI 1.3 to 7.3), and ankle brachial index <0.9 (OR, 2.2; 95% CI, 0.9 to 5.2). The prevalence of >or=50% asymptomatic CAD was also related to the extent of cervicocephalic atherosclerosis. CONCLUSIONS: About one fifth of patients with nondisabling, noncardioembolic ischemic stroke or transient ischemic attack have >or=50% asymptomatic CAD. In addition to vascular risk factors, the presence of >or=50% cervicocephalic artery stenosis is strongly related to >or=50% asymptomatic CAD. PMID- 20351237 TI - Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. AB - BACKGROUND: Obstructive sleep apnea (OSA) and central sleep apnea are common in patients with heart failure. We hypothesized that in such patients, severity of OSA is related to overnight rostral leg fluid displacement and increase in neck circumference, severity of central sleep apnea is related to overnight rostral fluid displacement and to sleep Pco(2), and continuous positive airway pressure alleviates OSA in association with prevention of fluid accumulation in the neck. METHODS AND RESULTS: In 57 patients with heart failure (ejection fraction or=50% of apneas and hypopneas obstructive) and a central-dominant group (>50% of events central). Patients with OSA received continuous positive airway pressure. In obstructive-dominant patients, there were inverse relationships between overnight change in leg fluid volume and both the overnight change in neck circumference (r=-0.780, P<0.001) and the apnea-hypopnea index (r=-0.881, P<0.001) but not transcutaneous Pco(2). In central-dominant patients, the overnight reduction in leg fluid volume correlated inversely with the apnea hypopnea index (r=-0.919, P<0.001) and the overnight change in neck circumference (r=-0.568, P=0.013) and directly with transcutaneous Pco(2) (r=0.569, P=0.009). Continuous positive airway pressure alleviated OSA in association with prevention of the overnight increase in neck circumference (P<0.001). CONCLUSIONS: Our findings suggest that nocturnal rostral fluid shift is a unifying concept contributing to the pathogenesis of both OSA and central sleep apnea in patients with heart failure. PMID- 20351238 TI - Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults. AB - BACKGROUND: Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. METHODS AND RESULTS: In this pooled analysis of 8 prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >or=60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100,000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100,000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100,000; 90% CI, 44 to 140) adults. Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults. PMID- 20351239 TI - DEFI 2005: a randomized controlled trial of the effect of automated external defibrillator cardiopulmonary resuscitation protocol on outcome from out-of hospital cardiac arrest. AB - BACKGROUND: Using automated external defibrillators (AEDs) that implement the Guidelines 2000 resuscitation protocol constrains administration of cardiopulmonary resuscitation (CPR) to <50% of AED connection time. We tested a different AED protocol aimed at increasing the CPR administered to patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: In a randomized controlled trial, patients with out-of-hospital cardiac arrest requiring defibrillation were treated with 1 of 2 AED protocols. In the control protocol, based on Guidelines 2000, sequences of up to 3 stacked countershocks were delivered, with rhythm analyses initially and after the first and second shocks. The study protocol featured 1 minute of CPR before the first shock, shorter CPR interruptions before and after each shock, and no stacked shocks. The primary end point was survival to hospital admission. Of 5107 out-of-hospital cardiac arrest patients connected to an AED, 1238 required defibrillation, and 845 were included in the final analysis. Study patients (n=421) had shorter preshock pauses (9 versus 19 seconds; P<0.001), had shorter postshock pauses (11 versus 33 seconds; P<0.001), and received more CPR (61% versus 48%; P<0.001) and fewer shocks (2.5 versus 2.9; P<0.001) than control patients (n=424). Similar proportions survived to hospital admission (43.2% versus 42.7%; P=0.87), survived to hospital discharge (13.3% versus 10.6%; P=0.19), achieved return of spontaneous circulation before physician arrival (47.0% versus 48.6%; P=0.65), and survived to 1 year (P=0.77). CONCLUSIONS: Following prompts from AEDs programmed with a protocol similar to Guidelines 2005, firefighters shortened pauses in CPR and improved overall hands on time, but survival to hospital admission of patients with ventricular fibrillation out-of-hospital cardiac arrest did not improve. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00139542. PMID- 20351240 TI - Gravitational influences and shifting propensity for sleep apnea: another source of heterogeneity or a new intervention target? PMID- 20351241 TI - Toward definitive trials and improved outcomes of cardiac arrest. PMID- 20351242 TI - Myosin complexed with ADP and blebbistatin reversibly adopts a conformation resembling the start point of the working stroke. AB - The powerstroke of the myosin motor is the basis of cell division and bodily movement, but has eluded empirical description due to the short lifetime and low abundance of intermediates during force generation. To gain insight into this process, we used well-established single-tryptophan and pyrene fluorescent sensors and electron microscopy to characterize the structural and kinetic properties of myosin complexed with ADP and blebbistatin, a widely used inhibitor. We found that blebbistatin does not weaken the tight actin binding of myosin.ADP, but unexpectedly it induces lever priming, a process for which the gamma-phosphate of ATP (or its analog) had been thought necessary. The results indicate that a significant fraction of the myosin.ADP.blebbistatin complex populates a previously inaccessible conformation of myosin resembling the start of the powerstroke. PMID- 20351243 TI - Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB. AB - PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 A resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction. PMID- 20351244 TI - Climate as a contributing factor in the demise of Angkor, Cambodia. AB - The "hydraulic city" of Angkor, the capitol of the Khmer Empire in Cambodia, experienced decades-long drought interspersed with intense monsoons in the fourteenth and fifteenth centuries that, in combination with other factors, contributed to its eventual demise. The climatic evidence comes from a seven-and a-half century robust hydroclimate reconstruction from tropical southern Vietnamese tree rings. The Angkor droughts were of a duration and severity that would have impacted the sprawling city's water supply and agricultural productivity, while high-magnitude monsoon years damaged its water control infrastructure. Hydroclimate variability for this region is strongly and inversely correlated with tropical Pacific sea surface temperature, indicating that a warm Pacific and El Nino events induce drought at interannual and interdecadal time scales, and that low-frequency variations of tropical Pacific climate can exert significant influence over Southeast Asian climate and society. PMID- 20351245 TI - Production and secretion of fatty acids in genetically engineered cyanobacteria. AB - Our purpose is to apply a fatty acid secretion strategy in photosynthetic microbial biofuel production, which will avoid the costly biomass recovery processes currently applied in algal biofuel systems. Starting with introducing acyl-acyl carrier protein thioesterases, we made five successive generations of genetic modifications into cyanobacterium Synechocystis sp. PCC 6803. The mutant strains were able to overproduce fatty acids (C10-C18) and secrete them into the medium at an efficiency of up to 133 +/- 12 mg/L of culture per day at a cell density of 1.5 x 10(8) cells/mL (0.23 g of dry weight/liter). Fatty acid secretion yields were increased by weakening the S layer and peptidoglycan layers. Although the fatty acid secreting strains had a long lag phase with many cells having damaged cell membranes when grown at low cell densities, these strains grew more rapidly in stationary phase and exhibited less cell damage than wild-type in a stationary culture. Our results suggest that fatty acid secreting cyanobacteria are a promising technology for renewable biofuel production. PMID- 20351246 TI - Elongated oligomers in beta2-microglobulin amyloid assembly revealed by ion mobility spectrometry-mass spectrometry. AB - The key to understanding amyloid disease is the characterization of oligomeric species formed during the early stages of fibril assembly. Here we have used electrospray ionisation-ion mobility spectrometry-mass spectrometry to identify and structurally characterize the oligomers formed during amyloid assembly from beta(2)-microglobulin (beta(2)m). Beta(2)m oligomers are shown to have collision cross-sections consistent with monomeric units arranged in elongated assemblies prior to fibril formation. Direct observation, separation, and quantification of transient oligomeric species reveals that monomers to tetramers are populated through the lag phase with no evidence for the significant population of larger oligomeric species under the conditions employed. The dynamics of each oligomeric species were monitored directly within the ensemble at concentrations commensurate with amyloid formation by observing the subunit exchange of (14)N- and (15)N-labeled oligomers. Analysis of the data revealed a decrease in oligomer dynamics concomitant with increasing oligomer size and the copopulation of dynamic dimeric and trimeric species with more stable trimeric and tetrameric species. The results presented map the events occurring during the lag phase of fibril formation and give a clear insight into the structural characteristics and dynamic nature of the beta(2)m oligomers, demonstrating the existence of elongated assemblies arising from an intact amyloidogenic protein during fibril formation. PMID- 20351247 TI - Fast molecular tracking maps nanoscale dynamics of plasma membrane lipids. AB - We describe an optical method capable of tracking a single fluorescent molecule with a flexible choice of high spatial accuracy (approximately 10-20 nm standard deviation or approximately 20-40 nm full-width-at-half-maximum) and temporal resolution (< 1 ms). The fluorescence signal during individual passages of fluorescent molecules through a spot of excitation light allows the sequential localization and thus spatio-temporal tracking of the molecule if its fluorescence is collected on at least three separate point detectors arranged in close proximity. We show two-dimensional trajectories of individual, small organic dye labeled lipids diffusing in the plasma membrane of living cells and directly observe transient events of trapping on < 20 nm spatial scales. The trapping is cholesterol-assisted and much more pronounced for a sphingo- than for a phosphoglycero-lipid, with average trapping times of approximately 15 ms and < 4 ms, respectively. The results support previous STED nanoscopy measurements and suggest that, at least for nontreated cells, the transient interaction of a single lipid is confined to macromolecular dimensions. Our experimental approach demonstrates that fast molecular movements can be tracked with minimal invasion, which can reveal new important details of cellular nano-organization. PMID- 20351248 TI - Protein folding at the membrane interface, the structure of Nogo-66 requires interactions with a phosphocholine surface. AB - Repair of damage to the central nervous system (CNS) is inhibited by the presence of myelin proteins that prevent axonal regrowth. Consequently, growth inhibitors and their common receptor have been identified as targets in the treatment of injury to the CNS. Here we describe the structure of the extracellular domain of the neurite outgrowth inhibitor (Nogo) in a membrane-like environment. Isoforms of Nogo are expressed with a common C terminus containing two transmembrane (TM) helices. The ectodomain between the two TM helices, Nogo-66, is active in preventing axonal growth [GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Nature 403:439-444]. We studied the structure of Nogo-66 alone and in the presence of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles and dodecylphosphocholine (DPC) micelles as membrane mimetics. We find that Nogo-66 is largely disordered when free in solution. However, when bound to a phosphocholine surface Nogo-66 adopts a unique, stable fold, even in the absence of TM anchors. Using paramagnetic probes and protein-DPC nuclear Overhauser effects (NOEs), we define portions of the growth inhibitor likely to be accessible on the cell surface. With these data we predict that residues (28-58) are available to bind the Nogo receptor, which is entirely consistent with functional assays. Moreover, the conformations and relative positions of side chains recognized by the receptor are now defined and provide a foundation for antagonist design. PMID- 20351249 TI - Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal cell differentiation. AB - Mediator recently has emerged as a central player in the direct transduction of signals from transcription factors to the general transcriptional machinery. In the case of nuclear receptors, in vitro studies have shown that the transcriptional coactivator function of the Mediator involves direct ligand dependent interactions of the MED1 subunit, through its two classical LxxLL motifs, with the receptor AF2 domain. However, despite the strong in vitro evidence, there currently is little information regarding in vivo functions of the LxxLL motifs either in MED1 or in other coactivators. Toward this end, we have generated MED1 LxxLL motif-mutant knockin mice. Interestingly, these mice are both viable and fertile and do not exhibit any apparent gross abnormalities. However, they do exhibit severe defects in pubertal mammary gland development. Consistent with this phenotype, as well as loss of the strong ligand-dependent estrogen receptor (ER)alpha-Mediator interaction, expression of a number of known ERalpha-regulated genes was down-regulated in MED1-mutant mammary epithelial cells and could no longer respond to estrogen stimulation. Related, estrogen stimulated mammary duct growth in MED1-mutant mice was also greatly diminished. Finally, additional studies show that MED1 is differentially expressed in different types of mammary epithelial cells and that its LxxLL motifs play a role in mammary luminal epithelial cell differentiation and progenitor/stem cell determination. Our results establish a key nuclear receptor- and cell-specific in vivo role for MED1 LxxLL motifs, through Mediator-ERalpha interactions, in mammary gland development. PMID- 20351250 TI - Active galactic nucleus feedback in clusters of galaxies. AB - Observations made during the last ten years with the Chandra X-ray Observatory have shed much light on the cooling gas in the centers of clusters of galaxies and the role of active galactic nucleus (AGN) heating. Cooling of the hot intracluster medium in cluster centers can feed the supermassive black holes found in the nuclei of the dominant cluster galaxies leading to AGN outbursts which can reheat the gas, suppressing cooling and large amounts of star formation. AGN heating can come in the form of shocks, buoyantly rising bubbles that have been inflated by radio lobes, and the dissipation of sound waves. PMID- 20351251 TI - Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. AB - The polycomb repressive complex (PRC) 1 protein Ring1B is an ubiquitin ligase that modifies nucleosomal histone H2A, a modification which plays a critical role in regulation of gene expression. We have shown that self-ubiquitination of Ring1B generates multiply branched, "noncanonical" polyubiquitin chains that do not target the ligase for degradation, but rather stimulate its activity toward histone H2A. This finding implies that Ring1B is targeted by a heterologous E3. In this study, we identified E6-AP (E6-associated protein) as a ligase that targets Ring1B for "canonical" ubiquitination and subsequent degradation. We further demonstrated that both the self-ubiquitination of Ring1B and its modification by E6-AP target the same lysines, suggesting that the fate of Ring1B is tightly regulated (e.g., activation vs. degradation) by the type of chains and the ligase that catalyzes their formation. As expected, inactivation of E6-AP affects downstream effectors: Ring1B and ubiquitinated H2A levels are increased accompanied by repressed expression of HoxB9, a PRC1 target gene. Consistent with these findings, E6-AP knockout mice display an elevated level of Ring1B and ubiquitinated histone H2A in various tissues, including cerebellar Purkinje neurons, which may have implications to the pathogenesis of Angelman syndrome, a neurodevelopmental disorder caused by deficiency of E6-AP in the brain. PMID- 20351252 TI - A joint x-ray and neutron study on amicyanin reveals the role of protein dynamics in electron transfer. AB - The joint x-ray/neutron diffraction model of the Type I copper protein, amicyanin from Paracoccus denitrificans was determined at 1.8 A resolution. The protein was crystallized using reagents prepared in D(2)O. About 86% of the amide hydrogen atoms are either partially or fully exchanged, which correlates well with the atomic depth of the amide nitrogen atom and the secondary structure type, but with notable exceptions. Each of the four residues that provide copper ligands is partially deuterated. The model reveals the dynamic nature of the protein, especially around the copper-binding site. A detailed analysis of the presence of deuterated water molecules near the exchange sites indicates that amide hydrogen exchange is primarily due to the flexibility of the protein. Analysis of the electron transfer path through the protein shows that residues in that region are highly dynamic, as judged by hydrogen/deuterium exchange. This could increase the rate of electron transfer by transiently shortening through-space jumps in pathways or by increasing the atomic packing density. Analysis of C-HX bonding reveals previously undefined roles of these relatively weak H bonds, which, when present in sufficient number can collectively influence the structure, redox, and electron transfer properties of amicyanin. PMID- 20351253 TI - Vicinal dihalonium ions: diprotonated and dimethylated chlorine [H2Cl2(2+), (CH3)2Cl2(2+)] and bromine [H2Br2(2+), (CH3)2Br2(2+)] dications. AB - High level ab initio calculations at the MP2/cc-pVTZ, CCSD(T)/cc-pVTZ, and CASSCF(6,6)/cc-pVTZ levels were performed to investigate geometries and energies of superelectrophilic diprotonated, and dimethylated molecular chlorine (Cl2) and bromine (Br2) dications. Diprotonated chlorine and diprotonated bromine dications 3a and 6a, respectively, were found to be lowest energy minima. The isomeric dications, 3b and 6b, are also minima on the potential energy surfaces but they are significantly less stable than the structures 3a and 6a by 33.6 and 30.9 kcal/mol, respectively. On the basis of computed G2 energies, proton affinities and related thermodynamic parameters were also calculated. Dications 3a and 6a have substantial kinetic barriers for deprotonation. Their homolytic dissociation are however facile. Dimethylated molecular chlorine and bromine dications 3g and 6g, respectively, were also found to be global energy minima. These vicinal dihalonium or the corresponding protosolvated species are expected to form either in the superacidic media or in the gas phase. PMID- 20351254 TI - Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels. AB - Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get some intuition into their organization by arranging them into well-known hierarchical layouts. These hierarchies, in turn, can be placed between the extremes of autocracies, with well-defined levels and clear chains of command, and democracies, without such defined levels and with more co-regulatory partnerships between regulators. In general, the presence of partnerships decreases the variation in information flow amongst nodes within a level, more evenly distributing stress. Here we study various regulatory networks (transcriptional, modification, and phosphorylation) for five diverse species, Escherichia coli to human. We specify three levels of regulators--top, middle, and bottom--which collectively govern the non-regulator targets lying in the lowest fourth level. We define quantities for nodes, levels, and entire networks that measure their degree of collaboration and autocratic vs. democratic character. We show individual regulators have a range of partnership tendencies: Some regulate their targets in combination with other regulators in local instantiations of democratic structure, whereas others regulate mostly in isolation, in more autocratic fashion. Overall, we show that in all networks studied the middle level has the highest collaborative propensity and coregulatory partnerships occur most frequently amongst midlevel regulators, an observation that has parallels in corporate settings where middle managers must interact most to ensure organizational effectiveness. There is, however, one notable difference between networks in different species: The amount of collaborative regulation and democratic character increases markedly with overall genomic complexity. PMID- 20351255 TI - Residues in the central beta-hairpin of the DNA helicase of bacteriophage T7 are important in DNA unwinding. AB - The ring-shaped helicase of bacteriophage T7 (gp4), the product of gene 4, has basic beta-hairpin loops lining its central core where they are postulated to be the major sites of DNA interaction. We have altered multiple residues within the beta-hairpin loop to determine their role during dTTPase-driven DNA unwinding. Residues His-465, Leu-466, and Asn-468 are essential for both DNA unwinding and DNA synthesis mediated by T7 DNA polymerase during leading-strand DNA synthesis. Gp4-K467A, gp4-K471A, and gp4-K473A form fewer hexamers than heptamers compared to wild-type helicase and alone are deficient in DNA unwinding. However, they complement for the growth of T7 bacteriophage lacking gene 4. Single-molecule studies show that these three altered helicases support rates of leading-strand DNA synthesis comparable to that observed with wild-type gp4. Gp4-K467A, devoid of unwinding activity alone, supports leading-strand synthesis in the presence of T7 DNA polymerase. We propose that DNA polymerase limits the backward movement of the helicase during unwinding as well as assisting the forward movement necessary for strand separation. PMID- 20351256 TI - ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. AB - ErbB3/HER3 is one of four members of the human epidermal growth factor receptor (EGFR/HER) or ErbB receptor tyrosine kinase family. ErbB3 binds neuregulins via its extracellular region and signals primarily by heterodimerizing with ErbB2/HER2/Neu. A recently appreciated role for ErbB3 in resistance of tumor cells to EGFR/ErbB2-targeted therapeutics has made it a focus of attention. However, efforts to inactivate ErbB3 therapeutically in parallel with other ErbB receptors are challenging because its intracellular kinase domain is thought to be an inactive pseudokinase that lacks several key conserved (and catalytically important) residues-including the catalytic base aspartate. We report here that, despite these sequence alterations, ErbB3 retains sufficient kinase activity to robustly trans-autophosphorylate its intracellular region--although it is substantially less active than EGFR and does not phosphorylate exogenous peptides. The ErbB3 kinase domain binds ATP with a K(d) of approximately 1.1 microM. We describe a crystal structure of ErbB3 kinase bound to an ATP analogue, which resembles the inactive EGFR and ErbB4 kinase domains (but with a shortened alphaC-helix). Whereas mutations that destabilize this configuration activate EGFR and ErbB4 (and promote EGFR-dependent lung cancers), a similar mutation conversely inactivates ErbB3. Using quantum mechanics/molecular mechanics simulations, we delineate a reaction pathway for ErbB3-catalyzed phosphoryl transfer that does not require the conserved catalytic base and can be catalyzed by the "inactive-like" configuration observed crystallographically. These findings suggest that ErbB3 kinase activity within receptor dimers may be crucial for signaling and could represent an important therapeutic target. PMID- 20351257 TI - Oxidation state of the XRCC1 N-terminal domain regulates DNA polymerase beta binding affinity. AB - Formation of a complex between the XRCC1 N-terminal domain (NTD) and DNA polymerase beta (Pol beta) is central to base excision repair of damaged DNA. Two crystal forms of XRCC1-NTD complexed with Pol beta have been solved, revealing that the XRCC1-NTD is able to adopt a redox-dependent alternate fold, characterized by a disulfide bond, and substantial variations of secondary structure, folding topology, and electrostatic surface. Although most of these structural changes occur distal to the interface, the oxidized XRCC1-NTD forms additional interactions with Pol beta, enhancing affinity by an order of magnitude. Transient disulfide bond formation is increasingly recognized as an important molecular regulatory mechanism. The results presented here suggest a paradigm in DNA repair in which the redox state of a scaffolding protein plays an active role in organizing the repair complex. PMID- 20351258 TI - Assessing respondent-driven sampling. AB - Respondent-driven sampling (RDS) is a network-based technique for estimating traits in hard-to-reach populations, for example, the prevalence of HIV among drug injectors. In recent years RDS has been used in more than 120 studies in more than 20 countries and by leading public health organizations, including the Centers for Disease Control and Prevention in the United States. Despite the widespread use and growing popularity of RDS, there has been little empirical validation of the methodology. Here we investigate the performance of RDS by simulating sampling from 85 known, network populations. Across a variety of traits we find that RDS is substantially less accurate than generally acknowledged and that reported RDS confidence intervals are misleadingly narrow. Moreover, because we model a best-case scenario in which the theoretical RDS sampling assumptions hold exactly, it is unlikely that RDS performs any better in practice than in our simulations. Notably, the poor performance of RDS is driven not by the bias but by the high variance of estimates, a possibility that had been largely overlooked in the RDS literature. Given the consistency of our results across networks and our generous sampling conditions, we conclude that RDS as currently practiced may not be suitable for key aspects of public health surveillance where it is now extensively applied. PMID- 20351259 TI - Transcriptional activation in the context of repression mediated by archaeal histones. AB - Many archaea (including all the methanogens, nearly all euryarchaeotes, and some crenarchaeotes) use histones as components of the chromatin that compacts their genomes. The archaeal histones are homo- and heterodimers that pair on DNA to form tetrasomes (as the eukaryotic histones H3 and H4 do). The resulting DNA packaging is known to interfere with assembly of the archaeal transcription apparatus at promoters; the ability of transcriptional activation to function in repressive archaeal chromatin has not yet been explored in vitro. Using four of the Methanocaldococcus jannaschii (Mja) histones, we have examined activation of the model Mja rb2 transcription unit by the Mja transcriptional activator Ptr2 in this simplified-chromatin context. Using hydroxyl radical footprinting, we find that the Ptr2-specific rb2 upstream activating site is a preferred histone localizing site that nucleates histone: DNA-binding radiating from the rb2 promoter. Nevertheless, Ptr2 competes effectively with histones for access to the rb2 promoter and most potently activates transcription in vitro at histone concentrations that extensively coat DNA and essentially silence basal transcription. PMID- 20351260 TI - Structure of lactococcal phage p2 baseplate and its mechanism of activation. AB - Siphoviridae is the most abundant viral family on earth which infects bacteria as well as archaea. All known siphophages infecting gram+ Lactococcus lactis possess a baseplate at the tip of their tail involved in host recognition and attachment. Here, we report analysis of the p2 phage baseplate structure by X-ray crystallography and electron microscopy and propose a mechanism for the baseplate activation during attachment to the host cell. This approximately 1 MDa, Escherichia coli-expressed baseplate is composed of three protein species, including six trimers of the receptor-binding protein (RBP). RBPs host recognition domains point upwards, towards the capsid, in agreement with the electron-microscopy map of the free virion. In the presence of Ca(2+), a cation mandatory for infection, the RBPs rotated 200 degrees downwards, presenting their binding sites to the host, and a channel opens at the bottom of the baseplate for DNA passage. These conformational changes reveal a novel siphophage activation and host-recognition mechanism leading ultimately to DNA ejection. PMID- 20351261 TI - Measurement of red blood cell mechanics during morphological changes. AB - The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell's morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane's shear, area, and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery. PMID- 20351262 TI - Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes. AB - Episodic memory requires the hippocampus, which is thought to bind cortical inputs into conjunctive codes. Local field potentials (LFPs) reflect dendritic and synaptic oscillations whose temporal structure may coordinate cellular mechanisms of plasticity and memory. We now report that single-trial spatial memory performance in rats was predicted by the power comodulation of theta (4-10 Hz) and low gamma (30-50 Hz) rhythms in the hippocampus. Theta-gamma comodulation (TGC) was prominent during successful memory retrieval but was weak when memory failed or was unavailable during spatial exploration in sample trials. Muscimol infusion into medial septum reduced the probability of TGC and successful memory retrieval. In contrast, patterned electrical stimulation of the fimbria-fornix increased TGC in amnestic animals and partially rescued memory performance in the water maze. The results suggest that TGC accompanies memory retrieval in the hippocampus and that patterned brain stimulation may inform therapeutic strategies for cognitive disorders. PMID- 20351263 TI - A rice high-affinity potassium transporter (HKT) conceals a calcium-permeable cation channel. AB - Plant high-affinity K(+) transport (HKT) proteins are so named because of their relation to bacterial and fungal transporters that mediate high-affinity K(+) uptake. The view that HKT family members are sodium-selective uniporters or sodium-potassium symporters is widely held. We have found that one of the rice HKT proteins also functions as a Ca(2+)-permeable cation channel that conducts current carried by a wide range of monovalent and divalent cations. The HKT rice gene, named OsHKT2;4, is expressed in several cell types, including root hairs and vascular parenchyma cells. The protein is localized to the plasma membrane, thereby providing a mechanism for cation uptake and extrusion. This finding goes against firmly entrenched dogma in showing that HKT proteins can function as both ion carriers and channels. The study further extends the function of HKT proteins to Ca(2+)-linked processes and, in so doing, defines a previously undescribed type of Ca(2+)-permeable cation channels in plants. The work also raises questions about the evolutionary changes in this protein family following the divergence of monocots and dicots. PMID- 20351264 TI - Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes. AB - Cortical endoplasmic reticulum (cER) is a permanent feature of yeast cells but occurs transiently in most animal cell types. Ist2p is a transmembrane protein that permanently localizes to the cER in yeast. When Ist2 is expressed in mammalian cells, it induces abundant cER containing Ist2. Ist2 cytoplasmic C terminal peptide is necessary and sufficient to induce cER. This peptide sequence resembles classic coat protein complex I (COPI) coatomer protein-binding KKXX signals, and indeed the dimerized peptide binds COPI in vitro. Controlled dimerization of this peptide induces cER in cells. RNA interference experiments confirm that coatomer is required for cER induction in vivo, as are microtubules and the microtubule plus-end binding protein EB1. We suggest that Ist2 dimerization triggers coatomer binding and clustering of this protein into domains that traffic at the microtubule growing plus-end to generate the cER beneath the plasma membrane. Sequences similar to the Ist2 lysine-rich tail are found in mammalian STIM proteins that reversibly induce the formation of cER under calcium control. PMID- 20351265 TI - Myosin-dependent endoplasmic reticulum motility and F-actin organization in plant cells. AB - Plants exhibit an ultimate case of the intracellular motility involving rapid organelle trafficking and continuous streaming of the endoplasmic reticulum (ER). Although it was long assumed that the ER dynamics is actomyosin-driven, the responsible myosins were not identified, and the ER streaming was not characterized quantitatively. Here we developed software to generate a detailed velocity-distribution map for the GFP-labeled ER. This map revealed that the ER in the most peripheral plane was relatively static, whereas the ER in the inner plane was rapidly streaming with the velocities of up to approximately 3.5 microm/sec. Similar patterns were observed when the cytosolic GFP was used to evaluate the cytoplasmic streaming. Using gene knockouts, we demonstrate that the ER dynamics is driven primarily by the ER-associated myosin XI-K, a member of a plant-specific myosin class XI. Furthermore, we show that the myosin XI deficiency affects organization of the ER network and orientation of the actin filament bundles. Collectively, our findings suggest a model whereby dynamic three-way interactions between ER, F-actin, and myosins determine the architecture and movement patterns of the ER strands, and cause cytosol hauling traditionally defined as cytoplasmic streaming. PMID- 20351266 TI - HuR regulates the expression of stress-sensitive genes and mediates inflammatory response in human umbilical vein endothelial cells. AB - An important aspect of vascular biology is the identification of regulators of stress-sensitive genes that play critical roles in mediating inflammatory response. Here, we show that expression of HuR in human umbilical vein endothelial cells is regulated by shear stress and statin treatment; HuR, in turn, regulates other stress-sensitive genes such as Kruppel-like factor 2 (Klf2), endothelial nitric oxide synthase (eNOS), and bone morphogenic protein 4 (BMP-4). We found that siRNA knockdown of HuR-inhibited inflammatory responses in endothelial cells, including ICAM-1 and VCAM-1 up-regulation, NFkappaB phosphorylation, and adhesion of monocytes. Tissue staining of the mouse aorta revealed increased HuR expression in the lesser curvature region of the arch that is exposed to disturbed flow, consistent with our in vitro data. Taken together, these results suggest that HuR plays a critical role in inducing inflammatory response of endothelial cells under mechanical and biochemical stresses. PMID- 20351267 TI - Mig-6 controls EGFR trafficking and suppresses gliomagenesis. AB - Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer that is driven by aberrant signaling of growth factor receptors, particularly the epidermal growth factor receptor (EGFR). EGFR signaling is tightly regulated by receptor endocytosis and lysosome-mediated degradation, although the molecular mechanisms governing such regulation, particularly in the context of cancer, remain poorly delineated. Here, high-resolution genomic profiles of GBM identified a highly recurrent focal 1p36 deletion encompassing the putative tumor suppressor gene, Mig-6. We show that Mig-6 quells the malignant potential of GBM cells and dampens EGFR signaling by driving EGFR into late endosomes and lysosome mediated degradation upon ligand stimulation. Mechanistically, this effect is mediated by the binding of Mig-6 to a SNARE protein STX8, a protein known to be required for late endosome trafficking. Thus, Mig-6 functions to ensure recruitment of internalized receptor to late endosomes and subsequently the lysosomal degradation compartment through its ability to specifically link EGFR and STX8 during ligand-stimulated EGFR trafficking. In GBM, the highly frequent loss of Mig-6 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Together, these data uncover a unique tumor suppression mechanism involving the regulation of receptor trafficking. PMID- 20351268 TI - Thermosensitive TRP channel pore turret is part of the temperature activation pathway. AB - Temperature sensing is crucial for homeotherms, including human beings, to maintain a stable body core temperature and respond to the ambient environment. A group of exquisitely temperature-sensitive transient receptor potential channels, termed thermoTRPs, serve as cellular temperature sensors. How thermoTRPs convert thermal energy (heat) into protein conformational changes leading to channel opening remains unknown. Here we demonstrate that the pathway for temperature dependent activation is distinct from those for ligand- and voltage-dependent activation and involves the pore turret. We found that mutant channels with an artificial pore turret sequence lose temperature sensitivity but maintain normal ligand responses. Using site-directed fluorescence recordings we observed that temperature change induces a significant rearrangement of TRPV1 pore turret that is coupled to channel opening. This movement is specifically associated to temperature-dependent activation and is not observed during ligand- and voltage dependent channel activation. These observations suggest that the turret is part of the temperature-sensing apparatus in thermoTRP channels, and its conformational change may give rise to the large entropy that defines high temperature sensitivity. PMID- 20351269 TI - Use of multiple dispersal pathways facilitates amphibian persistence in stream networks. AB - Although populations of amphibians are declining worldwide, there is no evidence that salamanders occupying small streams are experiencing enigmatic declines, and populations of these species seem stable. Theory predicts that dispersal through multiple pathways can stabilize populations, preventing extinction in habitat networks. However, empirical data to support this prediction are absent for most species, especially those at risk of decline. Our mark-recapture study of stream salamanders reveals both a strong upstream bias in dispersal and a surprisingly high rate of overland dispersal to adjacent headwater streams. This evidence of route-dependent variation in dispersal rates suggests a spatial mechanism for population stability in headwater-stream salamanders. Our results link the movement behavior of stream salamanders to network topology, and they underscore the importance of identifying and protecting critical dispersal pathways when addressing region-wide population declines. PMID- 20351270 TI - Alternative splicing of human papillomavirus type-16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation. AB - Certain types of human papillomaviruses (HPVs) are etiologically linked to cervical cancer. Their transforming capacity is encoded by a polycistronic premRNA, where alternative splicing leads to the translation of functional distinct proteins such as E6, E6*, and E7. Here we show that splicing of HPV16 E6/E7 ORF cassette is regulated by the epidermal growth factor (EGF) pathway. The presence of EGF was coupled to preferential E6 expression, whereas depletion of EGF, or treatment with EGF receptor (EGFR) neutralizing antibodies or the EGFR inhibitor tyrphostin AG1478, resulted in E6 exon exclusion in favor of E6*. As a consequence, increased p53 levels and enhanced translation of E7 with a subsequent reduction of the retinoblastoma protein pRb could be discerned. E6 exon exclusion upon EGF depletion was independent from promoter usage, mRNA stability, or selective mRNA transport. Time-course experiments and incubation with cycloheximide demonstrated that E6 alternative splicing is a direct and reversible effect of EGF signal transduction, not depending on de novo protein synthesis. Within this process, Erk1/2-kinase activation was the critical event for E6 exon inclusion, mediated by the upstream MAP kinase MEK1/2. Moreover, siRNA knockdown experiments revealed an involvement of splicing factors hnRNPA1 and hnRNPA2 in E6 exon exclusion, whereas the splicing factors Brm and Sam68 were found to promote E6 exon inclusion. Because there is a natural gradient of EGF and EGF receptor expression in the stratified epithelium, it is reasonable to assume that EGF modulates E6/E7 splicing during the viral life cycle and transformation. PMID- 20351271 TI - Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. AB - We identified a p53 target gene, phosphate-activated mitochondrial glutaminase (GLS2), a key enzyme in conversion of glutamine to glutamate, and thereby a regulator of glutathione (GSH) synthesis and energy production. GLS2 expression is induced in response to DNA damage or oxidative stress in a p53-dependent manner, and p53 associates with the GLS2 promoter. Elevated GLS2 facilitates glutamine metabolism and lowers intracellular reactive oxygen species (ROS) levels, resulting in an overall decrease in DNA oxidation as determined by measurement of 8-OH-dG content in both normal and stressed cells. Further, siRNA down-regulation of either GLS2 or p53 compromises the GSH-dependent antioxidant system and increases intracellular ROS levels. High ROS levels following GLS2 knockdown also coincide with stimulation of p53-induced cell death. We propose that GLS2 control of intracellular ROS levels and the apoptotic response facilitates the ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress. Indeed, overexpression of GLS2 reduces the growth of tumor cells and colony formation. Further, compared with normal tissue, GLS2 expression is reduced in liver tumors. Thus, our results provide evidence for a unique metabolic role for p53, linking glutamine metabolism, energy, and ROS homeostasis, which may contribute to p53 tumor suppressor function. PMID- 20351272 TI - Ventral striatal plasticity and spatial memory. AB - Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein-induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs long-term spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation. PMID- 20351273 TI - An unconventional myosin required for cell polarization and chemotaxis. AB - MyTH/FERM (myosin tail homology 4/band 4.1, ezrin, radixin, and moesin) myosins have roles in cellular adhesion, extension of actin-filled projections such as filopodia and stereocilia, and directional migration. The amoeba Dictyostelium discoideum expresses a simple complement of MyTH/FERM myosins, a class VII (M7) myosin required for cell-substrate adhesion and a unique myosin named MyoG. Mutants lacking MyoG exhibit a wide range of normal actin-based behaviors, including chemotaxis to folic acid, but have a striking defect in polarization and chemotaxis to cAMP. Although the myoG mutants respond to cAMP stimulation by increasing persistence and weakly increasing levels of cortical F-actin, they do not polarize; instead, they maintain a round shape and move slowly and randomly when exposed to a chemotactic gradient. The mutants also fail to activate and localize PI3K to the membrane closest to the source of chemoattractant. These data reveal a role for a MyTH/FERM myosin in mediating early chemotactic signaling and suggest that MyTH/FERM proteins have conserved roles in signaling and the generation of cell polarity. PMID- 20351274 TI - Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family. AB - The Wnt pathway regulates multiple biological and pathological processes including angiogenesis and inflammation. Here we identified a unique inhibitor of the Wnt pathway, SERPINA3K, a serine proteinase inhibitor with anti-inflammatory and angiogenic activities. SERPINA3K blocked the Wnt pathway activation induced by a Wnt ligand and by diabetes. Coprecipitation and ligand binding assay showed that SERPINA3K binds to low-density lipoprotein receptor-like protein 6 (LRP6) with a K(d) of 10 nM, in the range of its physiological concentration in the retina. Under the same conditions, SERPINA3K did not bind to the frizzled (Fz) receptor or low-density lipoprotein receptor. Further, SERPINA3K bound to LRP6 at the extracellular domain and blocked its dimerization with the Fz receptor induced by a Wnt ligand. The antagonizing activity of SERPINA3K to LRP6 was further confirmed by Xenopus axis duplication assay. These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. The blockade of Wnt signaling may represent a unifying mechanism for the anti-inflammatory and anti angiogenic effects of SERPINA3K. PMID- 20351275 TI - Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. AB - To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB FFIX additionally resulted in systemic delivery of F.IX antigen. This high responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment. PMID- 20351277 TI - Modulation of mismatch repair and genomic stability by miR-155. AB - Inactivation of mismatch repair (MMR) is the cause of the common cancer predisposition disorder Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), as well as 10-40% of sporadic colorectal, endometrial, ovarian, gastric, and urothelial cancers. Elevated mutation rates (mutator phenotype), including simple repeat instability [microsatellite instability (MSI)] are a signature of MMR defects. MicroRNAs (miRs) have been implicated in the control of critical cellular pathways involved in development and cancer. Here we show that overexpression of miR-155 significantly down regulates the core MMR proteins, hMSH2, hMSH6, and hMLH1, inducing a mutator phenotype and MSI. An inverse correlation between the expression of miR-155 and the expression of MLH1 or MSH2 proteins was found in human colorectal cancer. Finally, a number of MSI tumors with unknown cause of MMR inactivation displayed miR-155 overexpression. These data provide support for miR-155 modulation of MMR as a mechanism of cancer pathogenesis. PMID- 20351276 TI - Evaluating the Farming/Language Dispersal Hypothesis with genetic variation exhibited by populations in the Southwest and Mesoamerica. AB - The Farming/Language Dispersal Hypothesis posits that prehistoric population expansions, precipitated by the innovation or early adoption of agriculture, played an important role in the uneven distribution of language families recorded across the world. In this case, the most widely spread language families today came to be distributed at the expense of those that have more restricted distributions. In the Americas, Uto-Aztecan is one such language family that may have been spread across Mesoamerica and the American Southwest by ancient farmers. We evaluated this hypothesis with a large-scale study of mitochondrial DNA (mtDNA) and Y-chromosomal DNA variation in indigenous populations from these regions. Partial correlation coefficients, determined with Mantel tests, show that Y-chromosome variation in indigenous populations from the American Southwest and Mesoamerica correlates significantly with linguistic distances (r = 0.33 0.384; P < 0.02), whereas mtDNA diversity correlates significantly with only geographic distance (r = 0.619; P = 0.002). The lack of correlation between mtDNA and Y-chromosome diversity is consistent with differing population histories of males and females in these regions. Although unlikely, if groups of Uto-Aztecan speakers were responsible for the northward spread of agriculture and their languages from Mesoamerica to the Southwest, this migration was possibly biased to males. However, a recent in situ population expansion within the American Southwest (2,105 years before present; 99.5% confidence interval = 1,273-3,773 YBP), one that probably followed the introduction and intensification of maize agriculture in the region, may have blurred ancient mtDNA patterns, which might otherwise have revealed a closer genetic relationship between females in the Southwest and Mesoamerica. PMID- 20351278 TI - Disruption of the right temporoparietal junction with transcranial magnetic stimulation reduces the role of beliefs in moral judgments. AB - When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states (e.g., beliefs, intentions). Here, we test the hypothesis that the right temporoparietal junction (RTPJ), an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation (TMS) to disrupt neural activity in the RTPJ transiently before moral judgment (experiment 1, offline stimulation) and during moral judgment (experiment 2, online stimulation). In both experiments, TMS to the RTPJ led participants to rely less on the actor's mental states. A particularly striking effect occurred for attempted harms (e.g., actors who intended but failed to do harm): Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms. PMID- 20351279 TI - A theoretical framework for gene induction and experimental comparisons. AB - Ligand-mediated gene induction by steroid receptors is a multistep process characterized by a dose-response curve for gene product that follows a first order Hill equation. This behavior has classically been explained by steroid binding to receptor being the rate-limiting step. However, this predicts a constant potency of gene induction (EC(50)) for a given receptor-steroid complex, which is challenged by the findings that various cofactors/reagents can alter this parameter in a gene-specific manner. These properties put strong constraints on the mechanisms of gene induction and raise two questions: How can a first order Hill dose-response curve (FHDC) arise from a multistep reaction sequence, and how do cofactors modify potency? Here we introduce a theoretical framework in which a sequence of steps yields an FHDC for the final product as a function of the initial agonist concentration. An exact determination of all constants is not required to describe the final FHDC. The theory predicts mechanisms for cofactor/reagent effects on gene-induction potency and maximal activity and it assigns a relative order to cofactors in the sequence of steps. The theory is supported by several observations from glucocorticoid receptor-mediated gene induction. It identifies the mechanism and matches the measured dose-response curves for different concentrations of the combination of cofactor Ubc9 and receptor. It also predicts that an FHDC cannot involve the DNA binding of preformed receptor dimers, which is validated experimentally. The theory is general and can be applied to any biochemical reaction that shows an FHDC. PMID- 20351280 TI - Epigenomic analysis of Alu repeats in human ependymomas. AB - Global loss of DNA methylation has been known for decades as an epigenomic aberration associated with carcinogenesis and cancer progression. Loss of DNA methylation affects predominantly repetitive elements, which encompass >50% of the CpG dinucleotides present in the human genome. Because of the lack of an effective approach, no studies have been conducted to reveal such genome-wide methylation changes at a single-base resolution. To precisely determine the CpG sites with methylation loss during progression of pediatric intracranial ependymomas, we exploited a high-throughput bisulfite sequencing approach that simultaneously generates methylation profiles for thousands of Alu elements and their flanking sequences. Comparison of the methylation profiles of normal and tumor tissues revealed that the methylation status of the majority of CpG sites adjacent to or within Alu repeats remain unaltered, while a small set of CpG sites gain or lose methylation in ependymomas. Compared to the CpG sites with stable methylation level between normal control and ependymomas, the differentially methylated CpG sites are enriched in the sequences with low CpG density in the flanking regions of Alu repeats, rather than within the Alu sequences themselves. In addition, the CpG sites that are hypermethylated in ependymomas are proximal to CpG islands, whereas those that are hypomethylated are overrepresented in intergenic regions. Lastly, aberrant methylation of several genomic loci was confirmed to be associated with the aggressive primary tumors and the relapsed ependymomas. PMID- 20351281 TI - Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action. AB - MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8(+) T cells. Cells typically express approximately 100,000 class I molecules, or approximately 1 per 30,000 cellular proteins. Given "one protein, one peptide" representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products. PMID- 20351282 TI - PI3 kinase signaling is involved in Abeta-induced memory loss in Drosophila. AB - Multiple intracellular signals are altered in Alzheimer's disease brain tissues, including the PI3K/Akt pathway. However, the pathological relevance of such alterations is poorly understood. In vitro studies yield results that seem to be consistent with the conventional perception in which an up-regulation of the cell survival pathway, PI3K pathway, is protective in Alzheimer's disease pathogenesis. The current in vivo genetic approach, however, reveals that inhibition of the PI3K pathway leads to rescuing of the beta-amyloid peptide (Abeta)-induced memory loss in the Drosophila brain. We began our inquiry into the molecular basis of this memory loss by studying Abeta42-induced enhancement of long-term depression. We found that long-term depression is restored to a normal level through inhibition of PI3K activity. Abeta42-induced PI3K hyperactivity is directly confirmed by immunostaining of the PI3K phosphorylation targets, phospholipids. Such observations lead to the following demonstration that Abeta42-induced memory loss can be rescued through genetic silencing or pharmacological inhibition of PI3K functions. Our data suggest that Abeta42 stimulates PI3K, which in turn causes memory loss in association with an increase in accumulation of Abeta42 aggregates. PMID- 20351283 TI - Hrp48 attenuates Sxl expression to allow for proper notch expression and signaling in wing development. AB - Different signaling pathways are deployed in specific developmental contexts to generate sexually dimorphic traits. Recently, Sex-lethal (Sxl), the female determinant in Drosophila melanogaster, was shown to down-regulate Notch (N) signaling to accomplish sex-specific patterning. Paradoxically, however, both Sxl and N are ubiquitously expressed in all of the female cells. This raises a key question as to how, during monomorphic female development, N signaling escapes the negative impact of Sxl. Here, we uncover a regulatory loop involving Hrp48, an abundant Drosophila hnRNP, Sxl and N. Phenotypic consequences of the partial loss of hrp48 resemble that of N but are more pronounced in females than in males. Likewise, N levels are drastically diminished only in females. Interestingly, monomorphic female tissues including wing, eye and antennal discs display considerable increase in Sxl amounts. Finally, female-specific attenuation of N signaling is rescued upon simultaneous removal of Sxl. Thus, our data demonstrate that in monomorphic contexts, Hrp48 functions as a moderator of Sxl expression to achieve adequate levels of N receptor production and signaling. We propose that it is critical to modulate the activities of the master determinant underling sexual dimorphism, to ensure that it does not function inappropriately in monomorphic tissues and disrupt their development. PMID- 20351284 TI - Regulators of G-protein signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity. AB - G-protein heterotrimers, composed of a guanine nucleotide-binding G alpha subunit and an obligate G betagamma dimer, regulate signal transduction pathways by cycling between GDP- and GTP-bound states. Signal deactivation is achieved by G alpha-mediated GTP hydrolysis (GTPase activity) which is enhanced by the GTPase accelerating protein (GAP) activity of "regulator of G-protein signaling" (RGS) proteins. In a cellular context, RGS proteins have also been shown to speed up the onset of signaling, and to accelerate deactivation without changing amplitude or sensitivity of the signal. This latter paradoxical activity has been variably attributed to GAP/enzymatic or non-GAP/scaffolding functions of these proteins. Here, we validated and exploited a G alpha switch-region point mutation, known to engender increased GTPase activity, to mimic in cis the GAP function of RGS proteins. While the transition-state, GDP x AlF(4)(-)-bound conformation of the G202A mutant was found to be nearly identical to wild-type, G alpha(i1)(G202A) x GDP assumed a divergent conformation more closely resembling the GDP x AlF(4)(-) bound state. When placed within Saccharomyces cerevisiae G alpha subunit Gpa1, the fast-hydrolysis mutation restored appropriate dose-response behaviors to pheromone signaling in the absence of RGS-mediated GAP activity. A bioluminescence resonance energy transfer (BRET) readout of heterotrimer activation with high temporal resolution revealed that fast intrinsic GTPase activity could recapitulate in cis the kinetic sharpening (increased onset and deactivation rates) and blunting of sensitivity also engendered by RGS protein action in trans. Thus G alpha-directed GAP activity, the first biochemical function ascribed to RGS proteins, is sufficient to explain the activation kinetics and agonist sensitivity observed from G-protein-coupled receptor (GPCR) signaling in a cellular context. PMID- 20351285 TI - Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration. AB - Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. PMID- 20351286 TI - A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. AB - Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria, the targets of protective Abs and the basis of their inefficient acquisition are unknown. Addressing these knowledge gaps could accelerate malaria vaccine development. To this end, we developed a protein microarray containing approximately 23% of the Pf 5,400-protein proteome and used this array to probe plasma from 220 individuals between the ages of 2-10 years and 18-25 years in Mali before and after the 6-month malaria season. Episodes of malaria were detected by passive surveillance over the 8-month study period. Ab reactivity to Pf proteins rose dramatically in children during the malaria season; however, most of this response appeared to be short-lived based on cross-sectional analysis before the malaria season, which revealed only modest incremental increases in Ab reactivity with age. Ab reactivities to 49 Pf proteins measured before the malaria season were significantly higher in 8-10-year-old children who were infected with Pf during the malaria season but did not experience malaria (n = 12) vs. those who experienced malaria (n = 29). This analysis also provided insight into patterns of Ab reactivity against Pf proteins based on the life cycle stage at which proteins are expressed, subcellular location, and other proteomic features. This approach, if validated in larger studies and in other epidemiological settings, could prove to be a useful strategy for better understanding fundamental properties of the human immune response to Pf and for identifying previously undescribed vaccine targets. PMID- 20351287 TI - Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. AB - The autonomic nervous system regulates fuel availability and energy storage in the liver, adipose tissue, and other organs; however, the molecular components of this neural circuit are poorly understood. We sought to identify neural populations that project from the CNS indirectly through multisynaptic pathways to liver and epididymal white fat in mice using pseudorabies virus strains expressing different reporters together with BAC transgenesis and immunohistochemistry. Neurons common to both circuits were identified in subpopulations of the paraventricular nucleus of the hypothalamus (PVH) by double labeling with markers expressed in viruses injected in both sites. The lateral hypothalamus and arcuate nucleus of the hypothalamus and brainstem regions (nucleus of the solitary tract and A5 region) also project to both tissues but are labeled at later times. Connections from these same sites to the PVH were evident after direct injection of virus into the PVH, suggesting that these regions lie upstream of the PVH in a common pathway to liver and adipose tissue (two metabolically active organs). These common populations of brainstem and hypothalamic neurons express neuropeptide Y and proopiomelanocortin in the arcuate nucleus, melanin-concentrating hormone, and orexin in the lateral hypothalamus and in the corticotrophin-releasing hormone and oxytocin in the PVH. The delineation of this circuitry will facilitate a functional analysis of the possible role of these potential command-like neurons to modulate autonomic outflow and coordinate metabolic responses in liver and adipose tissue. PMID- 20351288 TI - Endoplasmic reticulum chaperone gp96 is essential for infection with vesicular stomatitis virus. AB - The envelope glycoprotein of vesicular stomatitis virus (VSV-G) enables viral entry into hosts as distant as insects and vertebrates. Because of its ability to support infection of most, if not all, human cell types VSV-G is used in viral vectors for gene therapy. However, neither the receptor nor any specific host factor for VSV-G has been identified. Here we demonstrate that infection with VSV and innate immunity via Toll-like receptors (TLRs) require a shared component, the endoplasmic reticulum chaperone gp96. Cells without gp96 or with catalytically inactive gp96 do not bind VSV-G. The ubiquitous expression of gp96 is therefore essential for the remarkably broad tropism of VSV-G. Cells deficient in gp96 also lack functional TLRs, which suggests that pathogen-driven pressure for TLR-mediated immunity maintains the broad host range of VSV-G by positively selecting for the ubiquitous expression of gp96. PMID- 20351289 TI - Attenuation of Forkhead signaling by the retinal determination factor DACH1. AB - The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box-containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis. PMID- 20351290 TI - Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana. AB - Karrikins are a class of seed germination stimulants identified in smoke from wildfires. Microarray analysis of imbibed Arabidopsis thaliana seeds was performed to identify transcriptional responses to KAR(1) before germination. A small set of genes that are regulated by KAR(1), even when germination is prevented by the absence of gibberellin biosynthesis or light, were identified. Light-induced genes, putative HY5-binding targets, and ABRE-like promoter motifs were overrepresented among KAR(1)-up-regulated genes. KAR(1) transiently induced the light signal transduction transcription factor genes HY5 and HYH. Germination of afterripened Arabidopsis seed was triggered at lower fluences of red light when treated with KAR(1). Light-dependent cotyledon expansion and inhibition of hypocotyl elongation were enhanced in the presence of germination-active karrikins. HY5 is important for the Arabidopsis hypocotyl elongation, but not seed germination, response to karrikins. These results reveal a role for karrikins in priming light responses in the emerging seedling, and suggest that the influence of karrikins on postfire ecology may not be limited to germination recruitment. PMID- 20351291 TI - FM echolocating bats shift frequencies to avoid broadcast-echo ambiguity in clutter. AB - Sonar broadcasts are followed by echoes at different delays from objects at different distances. When broadcasts are emitted rapidly in cluttered surroundings, echo streams from successive broadcasts overlap and cause ambiguity in matching echoes to corresponding broadcasts. To identify reactions to ambiguity in clutter, echolocating bats that emit multiple-harmonic FM sounds were trained to fly into a dense, extended array of obstacles (multiple rows of vertically hanging chains) while the sonar sounds the bat emitted were recorded with a miniature radio microphone carried by the bat. Flight paths were reconstructed from thermal-infrared video recordings. Successive rows of chains extended more than 6 m in depth, so each broadcast was followed by a series of echoes from multiple rows of chains that lasted up to 40 ms. Bats emitted sounds in pairs ("strobe groups") at short (20-40 ms) interpulse intervals (IPIs) alternating with longer IPIs (>50 ms). For many short IPIs, the stream of echoes from the first broadcast was still arriving when the second broadcast was emitted. This overlap caused ambiguity about matching echoes with broadcasts. Bats shifted frequencies of the first sound in each strobe group upward and the second sound downward by 3-6 kHz. When overlap and ambiguity ceased, frequency shifts ceased also. Frequency differences were small compared with the total broadcast band, which was 75-80 kHz wide, but the harmonic structure of echoes enhances the differences in spectrograms. Bats could use time-frequency comparisons of echoes with broadcasts to assign echoes to the corresponding broadcasts and thus avoid ambiguity. PMID- 20351292 TI - Contribution of SHP-1 protein tyrosine phosphatase to osmotic regulation of the transcription factor TonEBP/OREBP. AB - Hypertonicity activates the transcription factor TonEBP/OREBP, resulting in increased expression of osmoprotective genes, including those responsible for accumulation of organic osmolytes and heat-shock proteins. Phosphorylation of TonEBP/OREBP contributes to its activation. Several of the kinases that are involved were previously identified, but the phosphatases were not. In the present studies we screened a genomewide human phosphatase siRNA library in human embryonic kidney (HEK)293 cells for effects on TonEBP/OREBP transcriptional activity. We found that siRNAs against 57 phosphatases significantly alter TonEBP/OREBP transcriptional activity during normotonicity (290 mosmol/kg) or hypertonicity (500 mosmol/kg, NaCl added) or both. Most siRNAs increase TonEBP/OREBP activity, implying that the targeted phosphatases normally reduce that activity. We further studied in detail SHP-1, whose knockdown by its specific siRNA increases TonEBP/OREBP transcriptional activity at 500 mosmol/kg. We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity. SHP-1 coimmunoprecipitates with TonEBP/OREBP and vice versa, suggesting that they are physically associated in the cell. High NaCl inhibits the effect of SHP-1 on TonEBP/OREBP by increasing phosphorylation of SHP-1 on Ser591, which reduces its phosphatase activity and localization to the nucleus. Thus, TonEBP/OREBP is extensively regulated by phosphatases, including SHP-1, whose inhibition by high NaCl increases phosphorylation of TonEBP/OREBP at Y143, contributing to the nuclear localization and activation of TonEBP/OREBP. PMID- 20351293 TI - Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis. AB - The Wnt/planar cell polarity (PCP) pathway regulates directed cell movement during development and was recently found to play a critical role in endothelial cell proliferation and angiogenesis [Zhang Y, et al. (2006) Chem Biol 13:1001 1009; Masckauchan TN, et al. (2006) Mol Biol Cell 17:5163-5172]. However, the mechanisms by which PCP signaling components regulate angiogenesis remain unknown. We report that expression of a constitutively active C-terminal domain of Dishevelled-associated activator of morphogenesis 1 (DAAM1) selectively inhibited endothelial cell proliferation. Moreover, this activated construct suppressed endothelial cell migration and the ability to form coordinated networks in vivo and in vitro. Although constitutively active DAAM1 (CDAAM1) induced both actin polymerization and microtubule (MT) stabilization, the stabilization of MTs alone was sufficient to inhibit endothelial cell growth selectively. Inhibition of actin polymerization alone by jasplakinolide treatment failed to reproduce the inhibitory effects of CDAAM1. These results indicate that DAAM1 regulates endothelial cell growth through MT stabilization in a cell type selective manner and suggest that PCP signaling plays a pivotal role in angiogenesis by regulating MT stabilization. PMID- 20351294 TI - TRPC channels are necessary mediators of pathologic cardiac hypertrophy. AB - Pathologic hypertrophy of the heart is regulated through membrane-bound receptors and intracellular signaling pathways that function, in part, by altering Ca(2+) handling and Ca(2+)-dependent signaling effectors. Transient receptor potential canonical (TRPC) channels are important mediators of Ca(2+)-dependent signal transduction that can sense stretch or activation of membrane-bound receptors. Here we generated cardiac-specific transgenic mice that express dominant-negative (dn) TRPC3, dnTRPC6, or dnTRPC4 toward blocking the activity of the TRPC3/6/7 or TRPC1/4/5 subfamily of channels in the heart. Remarkably, all three dn transgenic strategies attenuated the cardiac hypertrophic response following either neuroendocrine agonist infusion or pressure-overload stimulation. dnTRPC transgenic mice also were partially protected from loss of cardiac functional performance following long-term pressure-overload stimulation. Importantly, adult myocytes isolated from hypertrophic WT hearts showed a unique Ca(2+) influx activity under store-depleted conditions that was not observed in myocytes from hypertrophied dnTRPC3, dnTRPC6, or dnTRPC4 hearts. Moreover, dnTRPC4 inhibited the activity of the TRPC3/6/7 subfamily in the heart, suggesting that these two subfamilies function in coordinated complexes. Mechanistically, inhibition of TRPC channels in transgenic mice or in cultured neonatal myocytes significantly reduced activity in the calcineurin-nuclear factor of activated T cells (NFAT), a known Ca(2+)-dependent hypertrophy-inducing pathway. Thus, TRPC channels are necessary mediators of pathologic cardiac hypertrophy, in part through a calcineurin-NFAT signaling pathway. PMID- 20351295 TI - Cell pole-specific activation of a critical bacterial cell cycle kinase. AB - Caulobacter crescentus integrates phospho-signaling pathways and transcription factor regulatory cascades to drive the cell cycle. Despite the essential role of the CckA histidine kinase in the control of cell cycle events, the factors that signal its activation at a specific time in the cell cycle have remained elusive. A conditional genetic screen for CckA mislocalization mutants, using automated fluorescence microscopy and an image processing platform, revealed that the essential DivL protein kinase promotes CckA localization, autophosphorylation, and activity at the new cell pole. The transient accumulation of DivL at the new cell pole, but not its kinase activity, is required for the localization and activation of CckA. Because DivL and CckA accumulate at the same cell pole after the initiation of DNA replication and were found to interact in vivo, we propose that DivL recruits CckA to the pole, thereby promoting its autophosphorylation and activity. PMID- 20351296 TI - A nocturnal mammal, the greater mouse-eared bat, calibrates a magnetic compass by the sun. AB - Recent evidence suggests that bats can detect the geomagnetic field, but the way in which this is used by them for navigation to a home roost remains unresolved. The geomagnetic field may be used by animals both to indicate direction and to locate position. In birds, directional information appears to be derived from an interaction of the magnetic field with either the sun or the stars, with some evidence suggesting that sunset/sunrise provides the primary directional reference by which a magnetic compass is calibrated daily. We demonstrate that homing greater mouse-eared bats (Myotis myotis) calibrate a magnetic compass with sunset cues by testing their homing response after exposure to an altered magnetic field at and after sunset. Magnetic manipulation at sunset resulted in a counterclockwise shift in orientation compared with controls, consistent with sunset calibration of the magnetic field, whereas magnetic manipulation after sunset resulted in no change in orientation. Unlike in birds, however, the pattern of polarization was not necessary for the calibration. For animals that occupy ecological niches where the sunset is rarely observed, this is a surprising finding. Yet it may indicate the primacy of the sun as an absolute geographical reference not only for birds but also within other vertebrate taxa. PMID- 20351297 TI - Integration of biomechanical compliance, leverage, and power in elephant limbs. AB - The structure and motion of elephant limbs are unusual compared with those of other animals. Elephants stand and move with straighter limbs (at least when walking), and have limited speed and gait. We devised novel experiments to examine how the limbs of elephants support and propel their mass and to explore the factors that may constrain locomotor performance in these largest of living land animals. We demonstrate that elephant limbs are remarkably compliant even in walking, which maintains low peak forces. Dogma defines elephant limbs as extremely "columnar" for effective weight support, but we demonstrate that limb effective mechanical advantage (EMA) is roughly one-third of that predicted for their size. EMA in elephants is actually smaller than that in horses, which are only one-tenth their mass; it is comparable to human limb values. EMA drops sharply with speed in elephants, as it does in humans. Muscle forces therefore must increase as the limbs become more flexed, and we show how this flexion translates to greater volumes of muscle recruited for locomotion and hence metabolic cost. Surprisingly, elephants use their forelimbs and hindlimbs in similar braking and propulsive roles, not dividing these functions among limbs as was previously assumed or as in other quadrupeds. Thus, their limb function is analogous to four-wheel-drive vehicles. To achieve the observed limb compliance and low peak forces, elephants synchronize their limb dynamics in the vertical direction, but incur considerable mechanical costs from limbs working against each other horizontally. PMID- 20351298 TI - A minority of foci or pan-nuclear apoptotic staining of gammaH2AX in the S phase after UV damage contain DNA double-strand breaks. AB - UV irradiation induces histone variant H2AX phosphorylated on serine 139 (gammaH2AX) foci and high levels of pan-nuclear gammaH2AX staining without foci, but the significance of this finding is still uncertain. We examined the formation of gammaH2AX and 53BP1 that coincide at sites of double-strand breaks (DSBs) after ionizing radiation. We compared UV irradiation and treatment with etoposide, an agent that causes DSBs during DNA replication. We found that during DNA replication, UV irradiation induced at least three classes of gammaH2AX response: a minority of gammaH2AX foci colocalizing with 53BP1 foci that represent DSBs at replication sites, a majority of gammaH2AX foci that did not colocalize with 53BP1 foci, and cells with high levels of pan-nuclear gammaH2AX without foci of either gammaH2AX or 53BP1. Ataxia-telangiectasia mutated kinase and JNK mediated the UV-induced pan-nuclear gammaH2Ax, which preceded and paralleled UV-induced S phase apoptosis. These high levels of pan-nuclear gammaH2AX were further increased by loss of the bypass polymerase Pol eta and inhibition of ataxia-telangiectasia and Rad3-related, but the levels required the presence of the damage-binding proteins of excision repair xeroderma pigmentosum complementation group A and C proteins. DSBs, therefore, represent a small variable fraction of UV-induced gammaH2AX foci dependent on repair capacity, and they are not detected within high levels of pan-nuclear gammaH2AX, a preapoptotic signal associated with ATM- and JNK-dependent apoptosis during replication. The formation of gammaH2AX foci after treatment with DNA-damaging agents cannot, therefore, be used as a direct measure of DSBs without independent corroborating evidence. PMID- 20351299 TI - Images in cardiovascular medicine. Dynamic right ventricular outflow tract obstruction due to a swinging echolucent cyst on interventricular septum in a 4 year-old girl. PMID- 20351300 TI - Letter by Winter et al regarding article, "Children and adults with congenital heart disease lost to follow-up: who and when?". PMID- 20351303 TI - Medication adherence in cardiovascular disease. PMID- 20351302 TI - Identifying patients at high risk of a cardiovascular event in the near future: current status and future directions: report of a national heart, lung, and blood institute working group. PMID- 20351304 TI - Images in cardiovascular medicine. Wide-field scanning laser ophthalmoscope imaging and angiography of central retinal vein occlusion. PMID- 20351306 TI - Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool. AB - Although the liver is known to be the main site of factor VIII (FVIII) production, other organs are probably also important for the regulation of FVIII secretion. However, the study of the regulation of extrahepatic FVIII production has been hampered by the lack of definitive identification of human tissues able to secrete FVIII. Recent studies have shown that lung endothelial cells can synthesize FVIII. We therefore studied the production of FVIII by endothelial cells purified from other vascular beds. Because physiologic stress results in a rapid elevation of FVIII, we also investigated whether endothelial cells can store FVIII and secrete it after treatment with agonists. Microvascular endothelial cells from lung, heart, intestine, and skin as well as endothelial cells from pulmonary artery constitutively secreted FVIII and released it after treatment with phorbol-myristate acetate and epinephrine. By contrast, endothelial cells from the aorta, umbilical artery and umbilical vein did not constitutively secrete FVIII or release it after treatment with agonists, probably because of a lack of FVIII synthesis. Extrahepatic endothelial cells from certain vascular beds therefore appear to be an important FVIII production and storage site with the potential to regulate FVIII secretion in chronic and acute conditions. PMID- 20351305 TI - IL-6 increases B-cell IgG production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production. AB - Src homology 2 domain-containing inositol 5-phosphatase (SHIP(-/-)) animals display an age-related increase in interleukin-6 (IL-6), a decrease in B lymphopoiesis, and an elevation in myelopoiesis. We investigated the origin of the IL-6 production and show that it is largely produced by peritoneal and splenic macrophages. IL-6 production by these macrophages is not a direct result of the loss of SHIP: IL-6 production is not spontaneous, is absent from bone marrow-derived macrophages, declines with prolonged culture of macrophages, and requires a stimulus present in vivo. The IL-6-rich peritoneal cavity of SHIP(-/-) mice shows more than 700-fold more immunoglobulin G (IgG) than wild-type, approximately 20% of which is aggregated or in an immune complex and contains B220(+) cells that secrete IgG. The SHIP-deficient peritoneal macrophages show evidence of IgG receptor stimulation. Animals lacking both the signal-transducing gamma-chain of IgG receptors and SHIP or Ig and SHIP produce less IL-6. The data indicate a feed-forward process in which peripheral macrophages, responding through IgG receptors to secreted IgG, produce IL-6, to support further B-cell production of IgG. Because of the proinflammatory phenotype of SHIP(-/-) animals, these findings emphasize the importance of IL-6-neutralizing strategies in autoimmune and proinflammatory diseases. PMID- 20351307 TI - A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE. AB - Among the different phenotypes of von Willebrand disease (VWD) type 2A, we identified a particular subgroup with a high frequency of 29%, characterized by a relative decrease of large von Willebrand factor (VWF) multimers and decreased A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13)-mediated proteolysis previously described in a single family as VWD type IIE (VWD2A/IIE). Phenotype and genotype of 57 patients from 38 unrelated families displaying a particular multimer pattern resembling the original VWD2A/IIE were studied. Pathogenicity of candidate mutations was confirmed by expression studies and phenotypic characterization of recombinant mutants. Specific mutations were identified in all patients. Twenty-two different mutations, most of them affecting cysteine residues, 17 of them being novel, are clustering mainly in the VWF D3 domain and correlate with the VWD2A/IIE phenotype. An intracellular retention of most mutants and/or a defect of multimerization seem to be the main pathogenic molecular mechanisms. ADAMTS13 proteolysis of mutant VWF was not different from wild-type VWF in a static assay, suggesting that reduced in vivo proteolysis is not an intrinsic property of mutant VWF. Our study identified a distinct VWD subtype with a common molecular background which contributes significantly to the heterogeneous spectrum of VWD. PMID- 20351308 TI - TRAF6 inhibits Th17 differentiation and TGF-beta-mediated suppression of IL-2. AB - Transforming growth factor-beta (TGF-beta) has an essential role in the generation of inducible regulatory T (iTreg) and T helper 17 (Th17) cells. However, little is known about the TGF-beta-triggered pathways that drive the early differentiation of these cell populations. Here, we report that CD4(+) T cells lacking the molecular adaptor tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) exhibit a specific increase in Th17 differentiation in vivo and in vitro. We show that TRAF6 deficiency renders T cells more sensitive to TGF-beta-induced Smad2/3 activation and proliferation arrest. Consistent with this, in TRAF6-deficient T cells, TGF-beta more effectively down regulates interleukin-2 (IL-2), a known inhibitor of Th17 differentiation. Remarkably, TRAF6-deficient cells generate normal numbers of Foxp3-expressing cells in iTreg differentiation conditions where exogenous IL-2 is supplied. These findings show an unexpected role for the adaptor molecule TRAF6 in Smad-mediated TGF-beta signaling and Th17 differentiation. Importantly, the data also suggest that a main function of TGF-beta in early Th17 differentiation may be the inhibition of autocrine and paracrine IL-2-mediated suppression of Th17 cell generation. PMID- 20351309 TI - An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells. AB - Arteriovenous-lymphatic endothelial cell fates are specified by the master regulators, namely, Notch, COUP-TFII, and Prox1. Whereas Notch is expressed in the arteries and COUP-TFII in the veins, the lymphatics express all 3 cell fate regulators. Previous studies show that lymphatic endothelial cell (LEC) fate is highly plastic and reversible, raising a new concept that all 3 endothelial cell fates may co-reside in LECs and a subtle alteration can result in a reprogramming of LEC fate. We provide a molecular basis verifying this concept by identifying a cross-control mechanism among these cell fate regulators. We found that Notch signal down-regulates Prox1 and COUP-TFII through Hey1 and Hey2 and that activated Notch receptor suppresses the lymphatic phenotypes and induces the arterial cell fate. On the contrary, Prox1 and COUP-TFII attenuate vascular endothelial growth factor signaling, known to induce Notch, by repressing vascular endothelial growth factor receptor-2 and neuropilin-1. We show that previously reported podoplanin-based LEC heterogeneity is associated with differential expression of Notch1 in human cutaneous lymphatics. We propose that the expression of the 3 cell fate regulators is controlled by an exquisite feedback mechanism working in LECs and that LEC fate is a consequence of the Prox1-directed lymphatic equilibrium among the cell fate regulators. PMID- 20351310 TI - Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood. AB - Exposed subendothelial collagen acts as a substrate for platelet adhesion and thrombus formation after vascular injury. Synthetic collagen-derived triple helical peptides, designated collagen-related peptide (CRP), GFOGER, and VWF-III, can specifically engage the platelet collagen receptors, glycoprotein VI and integrin alpha(2)beta(1), and plasma von Willebrand factor (VWF), respectively. Hitherto, the role of these 3 collagen-binding axes has been studied indirectly. Use of these uniform peptide substrates, rather than collagen fibers, provides independent control of each axis. Here, we use confocal imaging and novel image analysis techniques to investigate the effects of receptor-ligand engagement on platelet binding and activation during thrombus formation under flow conditions. At low shear (100s(-1) and 300s(-1)), both GFOGER and CRP are required for thrombus formation. At 1000s(-1), a combination of either CRP or GFOGER with VWF III induces comparable thrombus formation, and VWF-III increases thrombus deposition at all shear rates, being indispensable at 3000s(-1). A combination of CRP and VWF-III is sufficient to support extensive platelet deposition at 3000s( 1), with slight additional effect of GFOGER. Measurement of thrombus height after specific receptor blockade or use of altered proportions of peptides indicates a signaling rather than adhesive role for glycoprotein VI, and primarily adhesive roles for both alpha(2)beta(1) and the VWF axis. PMID- 20351311 TI - Histone deacetylases are critical targets of bortezomib-induced cytotoxicity in multiple myeloma. AB - Bortezomib is now widely used for the treatment of multiple myeloma (MM); however, its action mechanisms are not fully understood. Despite the initial results, recent investigations have indicated that bortezomib does not inactivate nuclear factor-kappaB activity in MM cells, suggesting the presence of other critical pathways leading to cytotoxicity. In this study, we show that histone deacetylases (HDACs) are critical targets of bortezomib, which specifically down regulated the expression of class I HDACs (HDAC1, HDAC2, and HDAC3) in MM cell lines and primary MM cells at the transcriptional level, accompanied by reciprocal histone hyperacetylation. Transcriptional repression of HDACs was mediated by caspase-8-dependent degradation of Sp1 protein, the most potent transactivator of class I HDAC genes. Short-interfering RNA-mediated knockdown of HDAC1 enhanced bortezomib-induced apoptosis and histone hyperacetylation, whereas HDAC1 overexpression inhibited them. HDAC1 overexpression conferred resistance to bortezomib in MM cells, and administration of the HDAC inhibitor romidepsin restored sensitivity to bortezomib in HDAC1-overexpressing cells both in vitro and in vivo. These results suggest that bortezomib targets HDACs via distinct mechanisms from conventional HDAC inhibitors. Our findings provide a novel molecular basis and rationale for the use of bortezomib in MM treatment. PMID- 20351312 TI - Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. AB - Dendritic cells (DCs) are key regulators of innate and acquired immunity. The maturation of DCs is directed by signal transduction events downstream of toll like receptors (TLRs) and other pattern recognition receptors. Here, we demonstrate that, in mouse DCs, TLR agonists stimulate a profound metabolic transition to aerobic glycolysis, similar to the Warburg metabolism displayed by cancer cells. This metabolic switch depends on the phosphatidyl inositol 3' kinase/Akt pathway, is antagonized by the adenosine monophosphate (AMP)-activated protein kinase (AMPK), and is required for DC maturation. The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10. Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses. PMID- 20351313 TI - 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. AB - The HSP90 client chaperone interaction stabilizes several important enzymes and antiapoptotic proteins, and pharmacologic inhibition of HSP90 results in rapid client protein degradation. Therefore, HSP90 inhibition is an attractive therapeutic approach when this protein is active, a phenotype commonly observed in transformed but not normal cells. However, preclinical studies with HSP90 inhibitors such as 17-AAG demonstrated depletion of only a subset of client proteins and very modest tumor cytotoxicity in chronic lymphocytic leukemia (CLL) cells. Herein, we describe another HSP90 inhibitor, 17-DMAG, which is cytotoxic to CLL but not normal lymphocytes. Treatment with 17-DMAG leads to depletion of the HSP90 client protein IKK, resulting in diminished NF-kappaB p50/p65 DNA binding, decreased NF-kappaB target gene transcription, and caspase-dependent apoptosis. Furthermore, treatment with 17-DMAG significantly decreased the white blood cell count and prolonged the survival in a TCL1-SCID transplant mouse model. The ability of 17-DMAG to function as an NF-kappaB inhibitor is of great interest clinically, as few currently available CLL drugs target this transcription factor. Therefore, the effect of 17-DMAG on NF-kappaB signaling pathways represents a novel therapy warranting further clinical pursuit in this and other B-cell lymphoproliferative disorders. PMID- 20351314 TI - Growth hormone (GH)-releasing hormone increases the expression of the dominant negative GH isoform in cases of isolated GH deficiency due to GH splice-site mutations. AB - An autosomal dominant form of isolated GH deficiency (IGHD II) can result from heterozygous splice site mutations that weaken recognition of exon 3 leading to aberrant splicing of GH-1 transcripts and production of a dominant-negative 17.5 kDa GH isoform. Previous studies suggested that the extent of missplicing varies with different mutations and the level of GH expression and/or secretion. To study this, wt-hGH and/or different hGH-splice site mutants (GH-IVS+2, GH-IVS+6, GH-ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GC-GHRHR). Upon GHRH stimulation, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed reduced hGH secretion and intracellular GH content when compared with cells expressing only wt-hGH, confirming the dominant-negative effect of 17.5-kDa isoform on the secretion of 22-kDa GH. Furthermore, increased amount of 17.5-kDa isoform produced after GHRH stimulation in cells expressing GH splice site mutants reduced production of endogenous rat GH, which was not observed after GHRH-induced increase in wt-hGH. In conclusion, our results support the hypothesis that after GHRH stimulation, the severity of IGHD II depends on the position of splice site mutation leading to the production of increasing amounts of 17.5-kDa protein, which reduces the storage and secretion of wt-GH in the most severely affected cases. Due to the absence of GH and IGF-I negative feedback in IGHD II, a chronic up-regulation of GHRH would lead to an increased stimulatory drive to somatotrophs to produce more 17.5-kDa GH from the severest mutant alleles, thereby accelerating autodestruction of somatotrophs in a vicious cycle. PMID- 20351315 TI - Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD 1 mice. AB - Bisphenol-A (BPA) is an endocrine-disrupting chemical used in the production of plastic food and beverage containers, leading to ubiquitous low-dose human exposure. It has been suggested that exposure to even low doses of BPA during development may be associated with increased susceptibility to obesity and diabetes later in life. Despite growing public concern, the existing empirical data are equivocal, prompting The Endocrine Society, the National Institute of Environmental Health Sciences, and others to call for further research. In this study, we tested the hypothesis that perinatal exposure to an ecologically relevant dose of BPA (1 part per billion via the diet) results in increased susceptibility to high-fat diet-induced obesity and glucose intolerance in adult CD-1 mice. The data did not support this hypothesis. In agreement with previous reports, we find that weanling mice exposed to BPA during gestation and lactation are heavier compared with control mice. We also find that BPA mice are longer than controls at 4 wk of age, but these differences are no longer apparent when the mice reach adulthood, even when tested on a high-fat diet. We conclude that this larger size-for-age represents a faster rate of growth early in development rather than an obese, diabetic phenotype in adulthood. PMID- 20351316 TI - Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin-releasing hormone-1 neurons via Y1 receptors. AB - Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH 1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH 1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R. PMID- 20351319 TI - Concurrent chemoradiotherapy for limited-stage extranodal natural killer/t-cell lymphoma, nasal type. PMID- 20351317 TI - Luteinizing hormone stimulates mammalian target of rapamycin signaling in bovine luteal cells via pathways independent of AKT and mitogen-activated protein kinase: modulation of glycogen synthase kinase 3 and AMP-activated protein kinase. AB - LH stimulates the production of cAMP in luteal cells, which leads to the production of progesterone, a hormone critical for the maintenance of pregnancy. The mammalian target of rapamycin (MTOR) signaling cascade has recently been examined in ovarian follicles where it regulates granulosa cell proliferation and differentiation. This study examined the actions of LH on the regulation and possible role of the MTOR signaling pathway in primary cultures of bovine corpus luteum cells. Herein, we demonstrate that activation of the LH receptor stimulates the phosphorylation of the MTOR substrates ribosomal protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1. The actions of LH were mimicked by forskolin and 8-bromo-cAMP. LH did not increase AKT or MAPK1/3 phosphorylation. Studies with pathway-specific inhibitors demonstrated that the MAPK kinase 1 (MAP2K1)/MAPK or phosphatidylinositol 3 kinase/AKT signaling pathways were not required for LH-stimulated MTOR/S6K1 activity. However, LH decreased the activity of glycogen synthase kinase 3Beta (GSK3B) and AMP-activated protein kinase (AMPK). The actions of LH on MTOR/S6K1 were mimicked by agents that modulated GSK3B and AMPK activity. The ability of LH to stimulate progesterone secretion was not prevented by rapamycin, a MTOR inhibitor. In contrast, activation of AMPK inhibited LH-stimulated MTOR/S6K1 signaling and progesterone secretion. In summary, the LH receptor stimulates a unique series of intracellular signals to activate MTOR/S6K1 signaling. Furthermore, LH-directed changes in AMPK and GSK3B phosphorylation appear to exert a greater impact on progesterone synthesis in the corpus luteum than rapamycin-sensitive MTOR-mediated events. PMID- 20351321 TI - Diagnosing alveolar rhabdomyosarcoma: morphology must be coupled with fusion confirmation. PMID- 20351322 TI - Impact of cytidine deaminase polymorphisms on toxicity after gemcitabine: the question is still ongoing. PMID- 20351323 TI - Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. AB - PURPOSE: Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib. PATIENTS AND METHODS: PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS: A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed. CONCLUSION: Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs. PMID- 20351324 TI - Patterns and correlates of adjuvant radiotherapy receipt after lumpectomy and after mastectomy for breast cancer. AB - PURPOSE: To use patient self-report to provide more valid estimates of whether radiotherapy (RT) is underutilized than possible with registry data, as well as to evaluate for disparities and the influence of preferences and provider interactions. METHODS: We considered 2,260 survey respondents who had nonmetastatic breast cancer, were age 20 to 79 years, were diagnosed between July 2005 and February 2007 in Detroit and Los Angeles, and reported to Surveillance, Epidemiology and End Results (SEER) registries (72% response rate). Survey responses were merged with SEER data. We assessed rates and correlates of RT receipt among all patients with invasive cancer receiving breast-conserving surgery (BCS) and among patients undergoing mastectomy with indications for RT (ie, positive lymph nodes or T3-4 tumors). RESULTS: Among 904 patients undergoing BCS with strong indications for RT, 95.4% received RT, and 77.6% received RT among the 135 patients undergoing mastectomy with strong indications (P < .001). Among 114 patients undergoing BCS with weaker indications (ie, elderly) for RT, 80.0% received treatment, and 47.5% received RT among the 164 patients undergoing mastectomy with weaker indications (T1N1, T2N1, or T3N0 disease; P < .001). On multivariate analysis, surgery type (P < .001), indication strength (P < .001), age (P = .005), comorbidity (P < .001), income (P = .03), patient desire to avoid RT (P < .001), level of surgeon involvement in decision to have radiation (P < .001), and SEER site (P < .001) were significantly associated with likelihood of RT receipt. CONCLUSION: RT receipt was consistently high across sociodemographic subgroups after BCS but was lower after mastectomy, even among patients with strong indications for treatment, in whom clinical benefit is similar. Surgeon involvement had a strong influence on RT receipt. PMID- 20351325 TI - Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. AB - PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC. PMID- 20351326 TI - Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. AB - PURPOSE: To determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the presence or absence of the PAX/FOXO1 fusion gene. PATIENTS AND METHODS: The fusion gene status of 210 histopathologically reviewed, clinically annotated rhabdomyosarcoma samples was determined by reverse transcriptase polymerase chain reaction. Kaplan-Meier analysis was used to assess event-free survival and overall survival in fusion gene-negative ARMS (ARMSn; n = 39), fusion gene-positive ARMS (ARMSp; n = 94), and ERMS (n = 77). A total of 101 RMS samples were also profiled for whole-genome expression, and 128 were profiled for genomic copy number imbalances. Profiling data were analyzed by supervised and unsupervised methods to compare features related to histopathology and fusion gene status. Results were also projected by meta-analysis techniques across three separate publically available data sets. RESULTS: Overall and event-free survival, frequency of metastases, and distribution of site at initial presentation were not significantly different between ARMSn and ERMS. Consistent with this, analysis of gene expression signatures could not reproducibly distinguish ARMSn from ERMS whereas fusion gene positive cases were distinct. ARMSn and ERMS frequently show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome. CONCLUSION: The clinical behavior and molecular characteristics of alveolar cases without a fusion gene are indistinguishable from embryonal cases and significantly different from fusion positive alveolar cases. This implies that fusion gene status irrespective of histology is a critical factor in risk stratification of RMS. PMID- 20351327 TI - Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. AB - PURPOSE: The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy. METHODS: Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity. RESULTS: Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity. CONCLUSION: Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity. PMID- 20351328 TI - Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome. AB - PURPOSE: Transformed mycosis fungoides (MF) and Sezary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)) plus thymoglobulin (for mismatched donors). Graft-versus host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate. RESULTS: Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached. CONCLUSION: Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect. PMID- 20351329 TI - Chemotherapy and survival benefit in elderly patients with advanced non-small cell lung cancer. AB - PURPOSE: Platinum-doublet chemotherapy regimens have been shown to extend survival in fit patients with advanced non-small-cell lung cancer (AdvNSCLC). This study extends recent population-based analyses focusing on treatment and survival benefit from use of platinum-doublet therapy, and addressing the role of performance status (PS). PATIENTS AND METHODS: Patients >or= 66 years with AdvNSCLC incident from 1997 to 2002 were identified in SEER-Medicare. Multivariate models examined tumor and patient characteristics associated with receipt of any chemotherapy and receipt of platinum-doublet compared with single agent therapy. Nonparametric models estimated treatment effects on survival. Models controlled for patient characteristics, including a novel method to use claims-based indicators to characterize PS. Propensity score analysis adjusted for confounding. RESULTS: Of the 21,285 patients, 25.8% received first-line chemotherapy. Multivariate analyses indicate lower use of any chemotherapy and platinum-based doublet regimens with increasing age, comorbidity, and poor PS. Receipt of any chemotherapy was associated with reduction in the adjusted hazard of death (0.558; 95% CI, 0.547 to 0.569) and an increase in adjusted 1-year survival from 11.6% (95% CI, 11.1 to 12.0) to 27.0% (95% CI, 26.4 to 27.6). Platinum-doublet receipt increased adjusted 1-year survival over single agents, from 19.4% (95% CI, 18.3 to 20.4) to 30.1% (95% CI, 28.9 to 31.4). CONCLUSION: Most elderly patients with AdvNSCLC do not receive chemotherapy, yet there are clear survival benefits, even with controls for age, comorbidity, and PS. The benefit of platinum-based doublet regimens is greater than single-agent chemotherapy. Claims-based proxy indicators of poor PS were independent predictors of treatment and merit further exploration. PMID- 20351330 TI - Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. AB - PURPOSE: Preoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT). PATIENTS AND METHODS: The primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m(2), docetaxel 20 mg/m(2) (intravenous, weekly x 5); capecitabine 1,000 mg/m(2) orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II. RESULTS: Fifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (>or= 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (< 5%). CONCLUSION: Preoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents. PMID- 20351331 TI - Improved survival of children with neuroblastoma between 1979 and 2005: a report of the Italian Neuroblastoma Registry. AB - PURPOSE: To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. PATIENTS AND METHODS: The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. RESULTS: Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward. CONCLUSION: The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN. PMID- 20351332 TI - Insulin-like growth factor receptor 1 (IGF1R) gene copy number is associated with survival in operable non-small-cell lung cancer: a comparison between IGF1R fluorescent in situ hybridization, protein expression, and mRNA expression. AB - PURPOSE: The purpose of this study was to characterize insulin-like growth factor 1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non-small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis. PATIENTS AND METHODS: One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181). RESULTS: IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis. CONCLUSION: IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value. PMID- 20351333 TI - Transition of care for young adult survivors of childhood and adolescent cancer: rationale and approaches. AB - PURPOSE: Young adult survivors of childhood and adolescent cancer are an ever growing population of patients, many of whom remain at lifelong risk for potentially serious complications of their cancer therapy. Yet research shows that many of these older survivors have deficient health-related knowledge and are not engaging in recommended health promotion and screening practices that could improve their long-term outcomes. The purpose of this review is to address these disparities by discussing how formal transition of care from pediatric to adult-focused survivorship services may help meet the unique medical, developmental, and psychosocial challenges of these young adults. DESIGN: Literature review and discussion. RESULTS: This article summarizes current research documenting the medical needs of young adult survivors, their suboptimal compliance with recommended follow-up, and the rationale, essential functions, current models, and innovative approaches for transition of follow-up care. CONCLUSION: Systematic health care transition constitutes the standard of care for young adult survivors of childhood cancer. In developing a transitional care program, it is necessary to consider the scope of services to be provided, available resources, and other local exigencies that help determine the optimal model for use. Additional research is needed to improve health services delivery to this population. Effective advocacy is needed, particularly in the United States, to ensure the availability of uninterrupted health insurance coverage for survivorship services in young adulthood. PMID- 20351334 TI - Phase III trial comparing vinflunine with docetaxel in second-line advanced non small-cell lung cancer previously treated with platinum-containing chemotherapy. AB - PURPOSE: To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m(2) or docetaxel 75 mg/m(2) every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety. RESULTS: Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed. CONCLUSION: This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC. PMID- 20351335 TI - Association between mammographic density and age-related lobular involution of the breast. AB - PURPOSE: Mammographic density and lobular involution are both significant risk factors for breast cancer, but whether these reflect the same biology is unknown. We examined the involution and density association in a large benign breast disease (BBD) cohort. PATIENTS AND METHODS: Women in the Mayo Clinic BBD cohort who had a mammogram within 6 months of BBD diagnosis were eligible. The proportion of normal lobules that were involuted was categorized by an expert pathologist as no (0%), partial (1% to 74%), or complete involution (>or= 75%). Mammographic density was estimated as the four-category parenchymal pattern. Statistical analyses adjusted for potential confounders and evaluated modification by parity and age. We corroborated findings in a sample of women with BBD from the Mayo Mammography Health Study (MMHS) with quantitative percent density (PD) and absolute dense and nondense area estimates. RESULTS: Women in the Mayo BBD cohort (n = 2,667) with no (odds ratio, 1.7; 95% CI, 1.2 to 2.3) or partial (odds ratio, 1.3; 95% CI, 1.0 to 1.6) involution had greater odds of high density (DY pattern) than those with complete involution (P trend < .01). There was no evidence for effect modification by age or parity. Among 317 women with BBD in the MMHS study, there was an inverse association between involution and PD (mean PD, 22.4%, 21.6%, 17.2%, for no, partial, and complete, respectively; P trend = .04) and a strong positive association of involution with nondense area (P trend < .01). No association was seen between involution and dense area (P trend = .56). CONCLUSION: We present evidence of an inverse association between involution and mammographic density. PMID- 20351336 TI - Which patients with cancer die at home? A study of six European countries using death certificate data. AB - PURPOSE: This study examines the proportion of cancer deaths occurring at home in six European countries in relation to illness and to demographic and health care factors. METHODS: Death certificate data of all cancer-related deaths in 2002 in Italy and 2003 in Belgium, the Netherlands, Norway, England, and Wales (N = 238,216) were linked with regional health care and area statistics. Multivariate binomial logistic regressions were performed to examine factors associated with dying at home. RESULTS: The percentage of all cancer deaths occurring at home was 12.8 in Norway, 22.1 in England, 22.7 in Wales, 27.9 in Belgium, 35.8 in Italy, and 45.4 in the Netherlands. Having solid cancers and being married increased the chances of dying at home in all countries. Being older and being a woman decreased the chances of dying at home, except in Italy where the opposite was the case. A higher educational attainment was associated with better chances of dying at home in Belgium, Italy, and Norway (countries where information on educational attainment was available). Better chances of dying at home were also associated with living in less urbanized areas in all countries but England. The number of hospital and care home beds seemed not to be universally strong predictors of dying at home. CONCLUSION: There are large country differences in the proportion of patients with cancer dying at home, and these seem influenced by country-specific cultural, social, and health care factors. Alongside cross national differences, country-specific aspects need to be considered in the development of policy strategies facilitating home death. PMID- 20351337 TI - Been there, done that, wrote the blog: the choices and challenges of supporting adolescents and young adults with cancer. AB - The purpose of this article is to review the current literature on the provision of support groups for adolescent and young adult (AYA) patients with cancer with a focus on the challenges that are faced by these initiatives. The value of group support to patients with cancer and particularly to this age group has been well documented. However, with the advent and increase in popularity of online support options, it is an opportune time to examine the options available to the AYA group and highlight areas that would benefit from further investigation. This article will review the literature on the need to provide support groups to this age group, the available options, and the challenges they face. PMID- 20351338 TI - Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. AB - Hypertension is a mechanism-based toxic effect of drugs that inhibit the vascular endothelial growth factor signaling pathway (VSP). Substantial evidence exists for managing hypertension as a chronic condition, but there are few prospectively collected data on managing acute hypertension caused by VSP inhibitors. The Investigational Drug Steering Committee of the National Cancer Institute convened an interdisciplinary cardiovascular toxicities expert panel to evaluate this problem, to make recommendations to the Cancer Therapy Evaluation Program on further study, and to structure an approach for safe management by treating physicians. The panel reviewed: the published literature on blood pressure (BP), hypertension, and specific VSP inhibitors; abstracts from major meetings; shared experience with the development of VSP inhibitors; and established principles of hypertension care. The panel generated a consensus report including the recommendations on clinical concerns summarized here. To support the greatest possible number of patients to receive VSP inhibitors safely and effectively, the panel had four recommendations: 1) conduct and document a formal risk assessment for potential cardiovascular complications, 2) recognize that preexisting hypertension will be common in cancer patients and should be identified and addressed before initiation of VSP inhibitor therapy, 3) actively monitor BP throughout treatment with more frequent assessments during the first cycle of treatment, and 4) manage BP with a goal of less than 140/90 mmHg for most patients (and to lower, prespecified goals in patients with specific preexisting cardiovascular risk factors). Proper agent selection, dosing, and scheduling of follow-up should enable maintaining VSP inhibition while avoiding the complications associated with excessive or prolonged elevation in BP. PMID- 20351339 TI - Targeting arterial remodeling: a key tile in the mosaic of the therapeutic effects of relaxin in cardiovascular disease. PMID- 20351340 TI - Ultrasound assessment of flow-mediated dilation. AB - Developed in 1992, the flow-mediated dilation test is now the most commonly used noninvasive assessment of vascular endothelial function in humans. Since its inception, scientists have refined their understanding of the physiology, analysis, and interpretation of this measurement. Recently, a significant growth of knowledge has added to our understanding and implementation of this clinically relevant research methodology. Therefore, this tutorial provides timely insight into recent advances and practical information related to the ultrasonic assessment of vascular endothelial function in humans. PMID- 20351342 TI - Aortic pulse wave velocity may have prognostic value not just for hypertension but also for abdominal aortic aneurysms. PMID- 20351341 TI - Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through tumor necrosis factor-alpha signaling. AB - Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy for which the pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I (AT(1)) receptor agonistic autoantibody (AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor alpha (TNF-alpha) is also associated with the disease; however, it is unknown whether this factor directly contributes to preeclamptic symptoms. Here we report that this autoantibody increases the proinflammatory cytokine TNF-alpha in the circulation of AT(1)-AA-injected pregnant mice but not in nonpregnant mice. Coinjection of AT(1)-AA with a TNF alpha neutralizing antibody reduced cytokine availability in AT(1)-AA-injected pregnant mice. Moreover, TNF-alpha blockade in AT(1)-AA-injected pregnant mice significantly attenuated the key features of preeclampsia. Autoantibody-induced hypertension was reduced from 131+/-4 to 110+/-4 mm Hg, and proteinuria was reduced from 212+/-25 to 155+/-23 microg of albumin per milligram of creatinine (both P<0.05). Injection of AT(1)-AA increased the serum levels of circulating soluble fms-like tyrosine kinase 1 and soluble endoglin (34.1+/-5.1, 2.4+/-0.3 ng/mL, respectively) and coinjection with the TNF-alpha blocker significantly reduced their levels (21.7+/-3.4 and 1.2+/-0.4 ng/mL, respectively). Renal damage and placental abnormalities were also decreased by TNF-alpha blockade. Lastly, the elevated circulating TNF-alpha in preeclamptic patients is significantly correlated with the AT(1)-AA bioactivity in our patient cohort. Similarly, the autoantibody, through AT(1) receptor-mediated TNF-alpha induction, contributed to increased soluble fms-like tyrosine kinase 1, soluble endoglin secretion, and increased apoptosis in cultured human villous explants. Overall, AT(1)-AA is a novel candidate that induces TNF-alpha, a cytokine that may play an important pathogenic role in preeclampsia. PMID- 20351343 TI - Relaxin therapy reverses large artery remodeling and improves arterial compliance in senescent spontaneously hypertensive rats. AB - Hypertension and aging are associated with large artery structural remodeling and stiffening, which are known to increase cardiovascular risk. Relaxin is a peptide hormone with potent antifibrotic action in multiple organs. Although relaxin is able to reduce peripheral vascular resistance and improve arterial compliance in rats, it remains unclear whether the improvement in compliance is indirectly attributed to a vasodilatory action or whether relaxin is able to reverse arterial remodeling and stiffening directly in aged hypertensive animals. Senescent spontaneously hypertensive rats (17 months old) were treated with relaxin for 2 weeks (0.5 mg/kg per day) followed by a 1-week washout period. We determined large artery compliance using in vivo and in vitro techniques and quantified arterial remodeling by morphological and chemical means. Relaxin therapy significantly reversed aortic remodeling (ie, increases in vessel size, wall thickness, and collagen content) and improved arterial compliance, effects independent of its vasodilatory action. In relaxin-treated spontaneously hypertensive rats, arterial collagen content showed a greater reduction (-31%; P<0.05) than that of elastin (-8%), resulting in an increased elastin:collagen ratio (0.63+/-0.03 versus 0.47+/-0.02; P<0.05). In conclusion, our results demonstrated that relaxin is potent in mediating reversal of arterial remodeling and improving arterial structural compliance in aged hypertensive rats. PMID- 20351344 TI - Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. AB - Vitamin D regulates the renin-angiotensin system (RAS) in experimental animals, but corresponding human data are limited. We examined the relation between plasma 25-hydroxyvitamin D and elements of the RAS in 184 normotensive individuals in high sodium balance; these included circulating levels of plasma renin activity and angiotensin II (Ang II) and the renal plasma flow response to infused Ang II, which is an indirect measure of the intrinsic RAS activity in the kidney. Compared with individuals with sufficient 25-hydroxyvitamin D levels (> or = 30.0 ng/mL), those with insufficiency (15.0 to 29.9 ng/mL) and deficiency (<15.0 ng/mL) had higher circulating Ang II levels (P for trend=0.03). Moreover, those with vitamin D deficiency had significantly blunted renal plasma flow responses to infused Ang II (mean decrease of 115 mL/min per 1.73 m(2) in renal plasma flow versus 145 mL/min per 1.73 m(2) among those with sufficient vitamin D levels; P for trend=0.009). Although plasma renin activity was higher among individuals with insufficient levels of vitamin D, the result was not statistically significant. These data suggest that low plasma 25-hydroxyvitamin D levels may result in upregulation of the RAS in otherwise healthy humans. PMID- 20351346 TI - Cyclotron production of 99mTc: an approach to the medical isotope crisis. PMID- 20351345 TI - Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. AB - We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone > or = 12 microg/24 hours and plasma renin activity < or = 1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects (P<0.05). Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide. Hyperaldosteronism causes intracardiac volume overload in patients with resistant hypertension in spite of conventional thiazide diuretic use. Mineralocorticoid receptor blockade induces rapid regression of left ventricular hypertrophy irrespective of aldosterone status. In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status. PMID- 20351351 TI - Imaging approaches to Parkinson disease. AB - Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusion-weighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas (18)F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with (18)F-dopamine PET or (123)I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes. PMID- 20351350 TI - Impact of dynamic 18F-FDG PET on the early prediction of therapy outcome in patients with high-risk soft-tissue sarcomas after neoadjuvant chemotherapy: a feasibility study. AB - Dynamic PET (dPET) studies with (18)F-FDG were performed in patients with soft tissue sarcomas who received neoadjuvant chemotherapy early in the course of therapy. The goal of the study was to evaluate the impact of early dPET studies and assess their value with regard to the therapy outcome using histopathologic data. METHODS: The evaluation included 31 patients with nonmetastatic soft-tissue sarcomas, who were treated with neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin. Patients were examined before the onset of therapy and after the completion of the second cycle. Histopathologic response served for reference and was available for 25 of 31 patients. Response was defined as less than 10% viable tumor tissue in the resected tumor tissue. The following parameters were retrieved from dPET studies: standardized uptake value (SUV); fractal dimension; 2-compartment model with computation of K(1), k(2), k(3), and k(4) (unit, 1/min); fractional blood volume; and influx according to Patlak. RESULTS: The mean SUV was 4.6 before therapy and 2.8 after 2 cycles. The mean influx was 0.059 before therapy and 0.043 after 2 cycles. The mean SUV was 3.9 in the responders and 5.5 in the nonresponders before therapy. After therapy, responders revealed a mean SUV of 2.5, whereas nonresponders had a mean SUV of 3.5. We used linear discriminant analysis to categorize the patients into 2 groups: response (n = 12) and nonresponse (n = 13). The correct classification rate of the responders (positive predictive value) was generally higher (>67%) than that for the nonresponders. Finally, the combined use of the 2 predictor variables, namely SUV and influx, of each study led to the highest accuracy of 83%. This combination was particularly useful for the prediction of responders (positive predictive value, 92%). The use of the percentage change in maximum SUV led to an accuracy of 58%. CONCLUSION: On the basis of these results, only a multiparameter analysis based on kinetic (18)F-FDG data of a baseline study and after 2 cycles is helpful for the early prediction of chemosensitivity in patients with soft-tissue sarcomas receiving neoadjuvant chemotherapy. PMID- 20351352 TI - Comparative toxicity and efficacy of combined radioimmunotherapy and antiangiogenic therapy in carcinoembryonic antigen-expressing medullary thyroid cancer xenograft. AB - A significant antitumor effect was previously observed with radioimmunotherapy using anti-carcinoembryonic antigen (131)I-F6 monoclonal antibody in medullary thyroid cancer-bearing nude mice. Nevertheless, no complete response was observed. As seen with chemotherapy, drugs targeting the tumor microenvironment might improve radioimmunotherapy efficacy. This study evaluated the toxicity and efficacy of combining radioimmunotherapy with thalidomide or a cyclopeptidic vascular endothelial growth inhibitor (CBOP11) in mice grafted with the TT human medullary thyroid cancer cell line. METHODS: Six to 10 nude mice treated with 92.5 MBq of (131)I-F6 in association with 200 mg/kg/d of oral thalidomide during 20 d by force-feeding or 0.45 mg/kg/d of CBOP11 during 25 d using subcutaneous minipumps were compared with control mice receiving either treatment or naked F6 or nonspecific (131)I-734. Combined therapies included (131)I-F6 at day 0 followed by thalidomide between days 20 and 40, thalidomide between days 0 and 20 followed by (131)I-F6 at day 25, (131)I-F6 at day 0 and CBOP11 between days 0 and 25, CBOP11 between days 0 and 25 followed by (131)I-F6 at day 25, and (131)I-F6 at day 0 followed by CBOP11 between days 20 and 45. Animal weight, hematologic toxicity, tumor volume, and serum calcitonin were monitored for the following 3 mo. Improvement of (125)I-F6 tumor biodistribution by antiangiogenic drug was studied after pretreatment by thalidomide. Follow-up of the tumor after combined antiangiogenic and radioimmunotherapy therapies was performed by histology studies. RESULTS: Combined associations, as compared with radioimmunotherapy alone, increased leukopenia but not thrombocytopenia. Tumor volume-quadrupling time (TVQT) was 22.8 +/- 3.3 d in the control group, 29.9 +/- 3.6 d in the group treated with thalidomide, 34.6 +/- 4.4 d in the group treated with CBOP11, and 51.0 +/- 2.8 d after radioimmunotherapy alone. As compared with radioimmunotherapy, TVQT was significantly longer (P < 0.01) after thalidomide followed by radioimmunotherapy (69.83 +/- 3.9), CBOP11 followed by radioimmunotherapy (71.3 +/- 6.1), and CBOP11-radioimmunotherapy in concomitance (64.2 +/- 6.1). Nevertheless, TVQT was not increased after radioimmunotherapy followed by thalidomide (48.8 +/- 4) and radioimmunotherapy followed by CBOP11 (56.8 +/- 4.8). Surprisingly, pretreatment by CBOP11 or thalidomide sensitized larger tumors (>300 mm(3)) to radioimmunotherapy. Change in calcitonin levels confirmed morphologic tumor response. Tumor uptake 24 h after injection of (125)I F6 was 4.5 +/- 0.6 percentage injected dose per gram (%ID/g) without pretreatment and 8.7 +/- 1.3 %ID/g with pretreatment by thalidomide. An increase of the antitumor effect observed using the antiangiogenic drug combined with radioimmunotherapy was correlated with a decrease of blood vessels shown by von Willebrand immunostaining. CONCLUSION: Pretreatment with antiangiogenic therapies improved radioimmunotherapy efficacy, with acceptable toxicity. Future investigations will be performed to understand how antiangiogenic agents sensitize large tumors to radioimmunotherapy. PMID- 20351353 TI - High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia. AB - The objective of this study was to examine (18)F-FDG uptake in microscopic tumors grown intraperitoneally in nude mice and to relate this to physiologic hypoxia and glucose transporter-1 (GLUT-1) expression. METHODS: Human colon cancer HT29 and HCT-8 cells were injected intraperitoneally into nude mice to generate disseminated tumors of varying sizes. After overnight fasting, animals, breathing either air or carbogen (95% O(2) + 5% CO(2)), were intravenously administered (18)F-FDG together with the hypoxia marker pimonidazole and cellular proliferation marker bromodeoxyuridine 1 h before sacrifice. Hoechst 33342, a perfusion marker, was administered 1 min before sacrifice. After sacrifice, the intratumoral distribution of (18)F-FDG was assessed by digital autoradiography of frozen tissue sections. Intratumoral distribution was compared with the distributions of pimonidazole, GLUT-1 expression, bromodeoxyuridine, and Hoechst 33342 as visualized by immunofluorescent microscopy. RESULTS: Small tumors (diameter, <1 mm) had high (18)F-FDG accumulation and were severely hypoxic, with high GLUT-1 expression. Larger tumors (diameter, 1-4 mm) generally had low (18)F FDG accumulation and were not significantly hypoxic, with low GLUT-1 expression. Carbogen breathing significantly decreased (18)F-FDG accumulation and tumor hypoxia in microscopic tumors but had little effect on GLUT-1 expression. CONCLUSION: There was high (18)F-FDG uptake in microscopic tumors that was spatially associated with physiologic hypoxia and high GLUT-1 expression. This enhanced uptake was abrogated by carbogen breathing, indicating that in the absence of physiologic hypoxia, high GLUT-1 expression, by itself, was insufficient to ensure high (18)F-FDG uptake. PMID- 20351354 TI - 68Ga-siderophores for PET imaging of invasive pulmonary aspergillosis: proof of principle. AB - The diagnosis of invasive pulmonary aspergillosis (IPA) is difficult and lacks specificity and sensitivity. In the pathophysiology of Aspergillus fumigatus, iron plays an essential role as a nutrient during infection. A. fumigatus uses a specific and highly efficient iron uptake mechanism based on iron-complexing ferric ion Fe(III) siderophores, which are a requirement for A. fumigatus virulence. We aimed to evaluate the potential of siderophores radiolabeled with (68)Ga, a positron emitter with complexing properties comparable to those of Fe(III), as a radiopharmaceutical for imaging IPA. METHODS: (68)Ga radiolabeling of the A. fumigatus siderophores desferri-triacetylfusarinine C (TAFC) and desferri-ferricrocin (FC) was performed at high specific activity. Stability, protein binding, and log P values were determined. In vitro uptake in A. fumigatus cultures was tested under varying conditions. Biodistribution was studied in healthy noninfected BALB/c mice, and uptake was studied in a model of A. fumigatus infection using immunosuppressed Lewis rats. RESULTS: High-specific activity (68)Ga labeling could be achieved, and resulting complexes were stable in serum, toward diethylenetriaminepentaacetic acid and Fe(III) challenge. Both siderophores showed hydrophilic properties ((68)Ga-TAFC, log P = -2.59; (68)Ga FC, log P = -3.17) with low values of protein binding for (68)Ga-TAFC (<2%). Uptake of both siderophores was highly dependent on the mycelial iron load and could be blocked with an excess (10 microM) of siderophore or NaN(3), indicating specific, energy-dependent uptake. In noninfected mice, (68)Ga-TAFC showed rapid renal excretion and low blood values (1.6 +/- 0.37 percentage injected dose per gram [%ID/g] at 30 min); in urine only intact (68)Ga-TAFC was detected. In contrast, (68)Ga-FC revealed high retention in blood (16.1 +/- 1.07 %ID/g at 90 min) and rapid metabolism. In the rat IPA model, lung uptake of (68)Ga-TAFC was dependent on the severity of infection, with less than 0.04 %ID/g in control rats (n = 5) and 0.29 +/- 0.11 %ID/g in mildly infected (n = 3) and 0.95 +/- 0.37 %ID/g in severely infected (n = 4) rats. PET showed focal accumulation in infected lung tissue. CONCLUSION: Both siderophores bound (68)Ga with high affinity, and (68)Ga-TAFC, especially, showed high stability. (68)Ga-TAFC displayed highly selective accumulation by A. fumigatus subspecies in vitro and in vivo. The high and specific uptake by A. fumigatus proves the potential of (68)Ga-labeled siderophores for the specific detection of A. fumigatus during infection. They hold promise as new PET agents for IPA. PMID- 20351355 TI - Dentin-derived BMP-2 and odontoblast differentiation. AB - It is known that stem cells from exfoliated deciduous teeth (SHED) can be induced to differentiate into odontoblasts. However, the nature of dentin-derived morphogenic signals required for dental pulp stem cell differentiation remains unclear. The hypothesis underlying this work is that dentin-derived Bone Morphogenetic Proteins (BMP) are necessary for the differentiation of SHED into odontoblasts. We observed that SHED express markers of odontoblastic differentiation (DSPP, DMP-1, MEPE) when seeded in human tooth slice/scaffolds and cultured in vitro, or implanted subcutaneously into immunodeficient mice. In contrast, SHED cultured in deproteinized tooth slice/scaffolds, or scaffolds without a tooth slice, do not express these markers. SHED express the BMP receptors BMPR-IA, BMPR-IB, and BMPR-II. Notably, blockade of BMP-2 signaling inhibited the expression of markers of odontoblastic differentiation by SHED cultured in tooth slice/scaffolds. Collectively, this work demonstrates that dentin-derived BMP-2 is required to induce the differentiation of SHED into odontoblasts. PMID- 20351356 TI - Evidence of intact histatins in the in vivo acquired enamel pellicle. AB - Understanding the composition and function of the acquired enamel pellicle (AEP) has been a major goal in oral biology. The aim of this study was to test the hypothesis that intact histatins are part of the in vivo AEP and that histatins after adsorption to HA have effects on in vitro enamel demineralization. This is the first study demonstrating the presence of intact histatins in vivo in the AEP. The in vitro experiments show that all naturally occurring histatins in the AEP have the potential to provide some level of protection against acid injury. PMID- 20351357 TI - Canine H3N8 influenza virus infection in dogs and mice. AB - An H3N8 influenza virus closely related to equine influenza virus was identified in racing greyhound dogs with respiratory disease in 2004 and subsequently identified in shelter and pet dogs. Pathologic findings in dogs spontaneously infected with canine influenza virus were compared with lesions induced in beagle and mongrel dogs following experimental inoculation with influenza A/canine/Florida/43/2004. BALB/c mice were inoculated with canine influenza virus to assess their suitability as an experimental model for viral pathogenesis studies. All dogs inoculated with virus developed necrotizing and hyperplastic tracheitis and bronchitis with involvement of submucosal glands as well as mild bronchiolitis and pneumonia. Viral antigen was identified in bronchial and tracheal epithelial cells of all dogs and in alveolar macrophages of several dogs. Many dogs that were spontaneously infected with virus also developed bacterial pneumonia, and greyhound dogs with fatal spontaneous infection developed severe pulmonary hemorrhage with hemothorax. Virus-inoculated BALB/c mice developed tracheitis, bronchitis, bronchiolitis, and mild pneumonia in association with viral antigen in airway epithelial cells and in type 2 alveolar epithelial cells. Virus was not detected in extrarespiratory sites in any animals. The results indicate that canine influenza virus infection consistently induces acute tracheitis and bronchitis in dogs. Mice may be a useful model for some pathogenesis studies on canine influenza virus infection. PMID- 20351358 TI - Neurologic disease in a pig. AB - Three 4-week-old Yorkshire-Hampshire cross piglets from a litter of 9 (7 liveborn) developed convulsions the day of weaning. They were subsequently obtunded, ataxic, and hypermetric and had intention tremors. An affected male pig was presented live for necropsy on day 5 postweaning. This animal was euthanatized and necropsied. No significant grossly visible postmortem lesions were found. Histologic examination of the brain disclosed laminar necrosis of the submeningeal cerebral and cerebellar cortices with replacement by broad sheets of gitter cells. Occasional cerebral and cerebellar leptomeningeal and parenchymal vessels were surrounded by lymphocytes with fewer eosinophils. The morphologic diagnosis was severe multifocal subcortical cerebral and cerebellar laminar necrosis with moderate multifocal lymphocytic and eosinophilic cerebral and cerebellar leptomeningeal and parenchymal perivasculitis. The history and histologic findings are consistent with an etiologic diagnosis of sodium ion intoxication. PMID- 20351360 TI - Neuronal embryonal tumors in fish. AB - This article describes 11 cases of neuronal embryonal neoplasia in captive adult teleost fish. Neoplasms were located within 1 or both eyes of 8 fish and the skin of 3 other fish. Ocular neoplasms most often presented as unilateral or bilateral exophthalmia. Seven ocular and 1 cutaneous mass were composed of small triangular (carrot-shaped) neoplastic cells with Flexner-Wintersteiner-type rosette formation. Mass location and histologic and ultrastructural features were suggestive of retinoblastomas. One ocular mass was composed of ribbons and rosettes of neoplastic cells with multiple areas of neuronal differentiation and was diagnosed as a teratoid medulloepithelioma. A cutaneous mass from an electric eel (Electrophorus electricus) consisted of rosettes and streams of elongate neoplastic cells. The epidermal electroreceptor (ampullary) organ was considered as an origin. Although distant metastases were not observed, neoplasms were generally locally aggressive with postexcision recurrence. There was occasional spread to or de novo occurrence within the contralateral eye. PMID- 20351359 TI - Systemic spironucleosis in 2 immunodeficient rhesus macaques (Macaca mulatta). AB - Spironucleus spp are parasites of fish and terrestrial vertebrates, including mice and turkeys, that rarely cause extraintestinal disease. Two rhesus macaques (Macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251. Both progressed to simian acquired immune deficiency syndrome within 1 year of inoculation and developed systemic protozoal infections in addition to common opportunistic infections, including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhesus adenovirus. In the first case, the protozoa were associated with colitis, multifocal abdominal abscessation, and lymphadenitis. In the second case, they were one of a number of organisms associated with extensive pyogranulomatous pneumonia and colitis. Ultrastructural, molecular, and phylogenetic analysis revealed the causative organism to be a species of Spironucleus closely related to Spironucleus meleagridis of turkeys. This report is the first of extraintestinal infection with Spironucleus sp in higher mammals and expands the list of opportunistic infections found in immunocompromised rhesus macaques. PMID- 20351361 TI - Reproductive and gender health. PMID- 20351368 TI - Acupuncture in the management of anxiety related to dental treatment: a case series. AB - BACKGROUND: Anxiety related to dental treatment is a common phenomenon that has a significant impact on the provision of appropriate dental care. The aim of this case series was to examine the effect of acupuncture given prior to dental treatment on the level of anxiety. METHODS: Eight dentists submitted 21 case reports regarding the treatment of dental anxiety. The level of anxiety was assessed by the Beck Anxiety Inventory (BAI). Only patients with moderate to severe anxiety (BAI score > or =16) were included. The remaining 20 patients, 16 women and 4 men, with a mean age of 40.3 years, had a median BAI score of 26.5 at baseline. The BAI score was assessed before and after the acupuncture treatment. All patients received acupuncture treatment for 5 min prior to the planned dental treatment using the points GV20 and EX6. RESULTS: There was a significant reduction in median value of BAI scores after treatment with acupuncture (26.5 reduced to 11.5; p<0.01), and it was possible to carry out the planned dental treatment in all 20 cases after acupuncture treatment. Previously this had only been possible in six cases. CONCLUSION: Acupuncture prior to dental treatment has a beneficial effect on the level of anxiety in patients with dental anxiety and may offer a simple and inexpensive method of treatment. However, the present results need to be tested in a larger randomised clinical trial in order to evaluate the effectiveness of the acupuncture treatment in patients with dental anxiety. PMID- 20351369 TI - The influence of baseline characteristics on response to a laser acupuncture intervention: an exploratory analysis. AB - OBJECTIVES: In clinical practice it is known that subjects vary in their response to acupuncture, but there is little data on what predicts the outcome. The aim of this study was to identify such predictors. METHOD: A secondary analysis was performed on data from 100 participants in a trial of laser and sham laser acupuncture for chronic non-specific low back pain. Multiple regression analysis was used to identify which baseline characteristics predicted pain change in the immediate, short and intermediate term. An analysis of covariance was performed based on these results to re-examine the primary result of the trial. RESULTS: Strong predictors of poor response were receipt of disability support pension, headache, the regular use of analgesics or previous failed back surgery. Higher pain scores or exacerbation of pain at baseline predicted a greater proportionate pain relief after the intervention. Adjusted analysis suggested a clinically important effect of laser compared to sham (p<0.05), at short term follow-up only. CONCLUSION: The findings of this study suggest which characteristics of patients with chronic low back pain are more likely to respond to laser acupuncture treatment, but require replication in other studies. The findings may not apply in other acupuncture interventions and treatment of different conditions. They may also be used to set selection criteria for future studies, and to aid interpreting the effect of baseline imbalances on trial results. PMID- 20351370 TI - Medical students and acupuncture: a short sharp placement experience! AB - BACKGROUND: Acupuncture and other complementary therapies (CTs) have become increasingly popular, with patients calling for more integrated care. It is questionable whether doctors know enough about these therapies to provide balanced and informed advice to patients and, given that most will come across patients accessing CTs, this is an area of concern. METHOD: This was an exploratory study of 40 students attending a placement at a CT service within an acute hospital trust in the UK. A questionnaire was given at the start of placement to record their scepticism towards CTs on a 0-10 scale and again, on placement completion. RESULT: Of the students attending, 73% (n=29) completed the questionnaire. There was a statistically significant reduction in scepticism scores assessed before and after placement (p<0.001). Of the respondents, 90% (n=26) were shown or attempted acupuncture. 76% of students reported that the placement would definitely influence the rate of CT referrals in their future practice. CONCLUSION: The placement experience provided students an opportunity to reconsider their attitudes towards CTs. The study was limited to one site and students independently elected to participate in the experience. Similar exposure could be of value to the wider medical student population, ultimately leading to more informed advice available to patients. Future research should include greater numbers, which could include a multi-site study. PMID- 20351371 TI - An experimental study on the self-report of acupuncture needle sensation during deep needling with bi-directional rotation. AB - BACKGROUND: Traditionally, acupuncturists manipulate needles to enhance sensations referred to as de qi or 'acupuncture needle sensation'. Acupuncture needle sensations are complex and quantifying the experience has been difficult. The aim of this crossover study was to measure self-reported needle sensation during deep and bi-directional rotated needling in 15 healthy volunteers. METHODS: Each participant received an experimental intervention consisting of superficial needling followed by deep needling and then deep needling with bi directional rotation. The control intervention consisted of superficial needling, followed by mock deep needling and then mock bi-directional rotation of the needle. The intensity of overall needle sensation was measured using a visual analogue scale (VAS). The subjective acupuncture sensation scale was used to capture component sensations. RESULTS: VAS scores were higher during 'deep' needle penetration when compared to superficial needling with mock deep insertion (p=0.0002). VAS scores were also higher during deep needling with bi-directional rotation compared to superficial needling with mock bi-directional rotation (p<0.0001). There were higher scores for total component sensation scores and for the sensation of throbbing during the deep needling with bi-directional rotation (p=0.001) when compared to superficial needling with mock bi-directional rotation. Tentative evidence that bi-directional needle rotation generated stabbing, tingling, heaviness, soreness and aching was also found. CONCLUSION: Bi directional rotation of a needle inserted into deep soft tissue produced higher acupuncture needle sensation intensities when compared to superficial needle insertion with mock deep penetration and bi-directional rotation. PMID- 20351372 TI - Is there any difference in human pupillary reaction when different acupuncture points are stimulated? AB - OBJECTIVES: To determine if there is any difference in pupillary response among different acupuncture stimulation sites. METHODS: The subjects were 14 healthy males who had no known eye diseases or abnormality in their pupils. They received five different interventions: no acupuncture stimulation (hereinafter 'no stimulation') and acupuncture stimulation at four sites (TE5, ST7, CV12 and ST36). The Latin square design was used to allocate stimulation order. For all acupuncture stimulation interventions, a disposable acupuncture needle was inserted superficially at the acupuncture point. Gentle repetitive tapping stimulation was applied manually during the subject's exhalation phase of respiration, for 90 s. The pupil diameter was continuously measured for 2 min before stimulation, during stimulation and for 2 min after stimulation. Statistical analysis was conducted on serial changes in pupil diameter during acupuncture stimulation on each respective site and during non-stimulation session by analysis of variance and Fisher (least significant difference) multiple comparison, with linear analysis using a mixed model. RESULTS: Pupil diameter reduction occurred at 30 s after stimulation on ST7 (p=0.008) and 60 s after stimulation (p=0.014) compared with pre-stimulation. The decrease of pupillary diameter occurred 60 s after stimulation on TE5 (p=0.028) compared with pre-stimulation. On ST36, CV12 and during the non-stimulation intervention, no significant change in the pupil diameter was observed. CONCLUSIONS: Pupillary reaction varies depending on the different stimulation sites. PMID- 20351373 TI - Short-term effect of acupuncture on intraocular pressure in healthy subjects. AB - PURPOSE: To evaluate the short-term effect of acupuncture on the intraocular pressure (IOP) in healthy subjects. METHODS: A randomised controlled double blinded trial was performed. 48 healthy volunteers (94 eyes) were randomly allocated to three groups: acupuncture group-19 subjects (38 eyes) were submitted to a 20 min session of acupuncture (GB1, GB14 and BL1); sham group-14 subjects (27 eyes) were submitted to a 20 min session of acupuncture with needles inserted in false points; and control group-15 subjects (29 eyes) who underwent no intervention. All subjects had the IOP measured by a masked investigator using Goldmann applanation tonometry immediately before intervention, as well as 20 min and 24 h after. RESULTS: The mean (SD) IOP in the acupuncture group was 17.9 (3.3) mm Hg at baseline, 16.4 (3.9) mm Hg at 20 min and 16.3 (3.3) mm Hg at 24 h. The mean (SD) IOP in the sham group was 18.6 (3.3) mm Hg at baseline, 17.7 (2.6) mm Hg at 20 min and 15.9 (3.6) mm Hg at 24 h. The mean (SD) IOP in the control group was 16.9 (3.5) mm Hg at baseline, 16.5 (3.8) mm Hg at 20 min and 15.8 (3.3) mm Hg at 24 h. There was no statistically significant difference in the IOP variation (post-intervention minus baseline measurements) between groups after 20 min (p=0.13) and 24 h (p=0.21). CONCLUSION: Acupuncture in the studied points did not produce significant short-term effect on the IOP of healthy individuals in comparison with control groups. PMID- 20351374 TI - Effect of acupuncture on salivary immunoglobulin A after a bout of intense exercise. AB - In the field of athletics, acupuncture has been used for treatment of injury, reduction of fatigue and management of physical condition. However, there is little information on the effect of acupuncture on the immune function in response to exercise. PURPOSE: The aim of this study was to examine the effect of acupuncture treatment on the mucosal immune function after a single period of intense exercise by measuring salivary immunoglobulin A (SIgA). METHODS: 12 healthy men (23.6+/-SEv 0.3 years) participated in this study with a crossover design. The subjects exercised on a bicycle equipped with an ergometer at 75% VO(2)max for 60 min. Acupuncture treatment was applied at LU6, LI4, ST36 and ST6, for 30 min after the exercise. The control treatment was rest without acupuncture and that the order of the treatment was randomised. We measured parameters including saliva flow rate, SIgA concentration, SIgA secretion rate, heart rate and plasma catecholamine concentration all before the exercise and at 1 h, 2 h, 3 h, 4 h and 24 h after the exercise. The visual analogue scale for self-perceived tiredness and the profile of mood states questionnaires were recorded before the exercise and at 24 h after the exercise. RESULT: Intense exercise-induced decrease of SIgA levels was attenuated by the acupuncture treatment. In contrast, the subjective fatigue score and psychological measurement were not affected by the acupuncture. CONCLUSION: Acupuncture treatment may attenuate the decrease in SIgA level induced by intense exercise. PMID- 20351375 TI - Validation of a simplified sham acupuncture technique for its use in clinical research: a randomised, single blind, crossover study. AB - OBJECTIVES: The validity of a new sham acupuncture technique was tested on acupuncture naive healthy subjects. METHODS: The procedure was tested in accupoints LI4 and ST6 in a randomised, single blind and crossover study. The participants were blind to which technique they received. 32 healthy volunteers (15 men, 17 women, aged between 20 and 62 years, mean age 34 years) were recruited at the Universidad de la Republica, Uruguay. Interventions Participants were randomly assigned to one of two groups: (1) real acupuncture or (2) sham acupuncture. After 30 min, the patients were 'needled' again in a crossover design. Main outcome measures A yes/no questionnaire was used to assess the credibility and characteristics of the procedure. RESULTS: For the credibility question (do you think you received real acupuncture?) no statistically significant group differences were evident before or after the crossover. Subjects who answered yes to this question ranged from 14/16 (87.5%) before crossover to 10/16 (62.5%) after crossover for the sham and 12/16 (75%) before crossover to 15/16 (93.8%) after crossover for the real acupuncture. The question that showed a significant difference (only after crossover) was the question, "did you feel the needle penetrating the skin?"; after crossover 12/16 (75%) subjects in the real acupuncture group said yes and 2/16 (12%) subjects in the sham group said yes to this question (p<0.01). CONCLUSIONS: These data suggests that this method is credible and constitutes a simple and inexpensive technique for use as a control in clinical research in acupuncture naive subjects. PMID- 20351376 TI - The Mae On Project: using acupuncture for symptom relief and improved quality of life for people living with HIV and AIDS in rural Thailand. AB - Acupuncture in combination with antiretroviral therapies is a potentially useful treatment for HIV-related symptom relief in resource-poor settings. Traditional Chinese medicine has a long history of being used to enhance immune function. In the setting of HIV, Chinese traditional medicine allows for symptom treatment without adding extra medications to a complex drug regime. This paper provides details of a project at Mae On Hospital in rural northern Thailand where allopathic/conventional treatments are used in tandem with acupuncture. A preliminary evaluation of the project suggests that an integrated approach to symptom relief is viewed positively by respondents receiving acupuncture, though further studies are required to confirm the association between acupuncture and symptom relief. The project also demonstrates the feasibility of developing a cost-effective acupuncture programme using local healthcare staff. PMID- 20351377 TI - Management of shoulder injuries using dry needling in elite volleyball players. AB - These case reports describe the short-term benefits of dry needling in shoulder injuries in four international female volleyball athletes during a month-long intense competitive phase, using both replicable subjective and objective measures. Dry needling of scapulohumeral muscles was carried out. Range of movement, strength and pain were assessed before and after treatment, with a functional assessment of pain immediately after playing and overhead activity, using the short form McGill Pain Questionnaire. All scores were improved post treatment and athletes were able to continue overhead activities. Previous studies have suggested that myofascial trigger points may cause significant functional weakness and reduced range of motion, with referred pain. Trigger point dry needling has been successful in treating athletes with myofascial pain and impingement symptoms but with only subjective improvement and not during a competitive phase. These cases support the use of dry needling in elite athletes during a competitive phase with short-term pain relief and improved function in shoulder injuries. It may help maintain rotator cuff balance and strength, reducing further pain and injury. PMID- 20351378 TI - A 54-year-old woman with degenerative back pain. AB - Back pain is a common symptom: up to 70% of UK adults experience this symptom by the age of 60 and most have moderate to severe pain. Back pain accounted for 12% of consultations to traditional acupuncturists in 2001 and is one of the most common reasons for consultation with an acupuncturist. This case report concerns a 54-year-old woman with metastatic breast cancer and degenerative lower back pain, which remained painful despite intensive pharmaceutical management and facet joint injection and was ultimately successfully managed with two 30 min acupuncture treatments 2 weeks apart, using eight points on the BL meridians. Acupuncture treatment using tender points was later trialled for neuropathic pain secondary to local recurrence in her mastectomy scar, however this was unsuccessful and inpatient hospice admission for further intensive pharmaceutical management was required. PMID- 20351379 TI - Electroacupuncture therapy for arthralgia and Raynaud's phenomenon in a patient with systemic lupus erythematosus. AB - A 45-year-old woman with systemic lupus erythematosus presented with multiple arthralgia, coldness in fingers and toes, and Raynaud's phenomenon. Electroacupuncture (EA) therapy was performed in two courses (14 treatment sessions) 1 month apart. A needle was inserted in the proximal (or medial) side of the painful joint and another needle was inserted in the distal (or lateral) side of the same joint and a 50 Hz stimulus was applied (3 s bursts with 1 s gaps) for 15 min. A visual analogue scale was used to evaluate pain intensity. Cold provocation testing was conducted before and after EA sessions to determine the vasomotor response. Visual analogue scale scores were lower after EA sessions than before. Before starting EA, the skin temperature of the right mid fingertip was 27.9 degrees C and that of the left mid fingertip was 28.3 degrees C. In contrast, after the EA sessions, the skin temperature of the right mid fingertip was 34.8 degrees C and that of the left mid fingertip was 34.7 degrees C. In the last EA session, the patient reported that the cold in her fingers and toes had eased and Raynaud's phenomenon, in which nail colour tone changed from white to red, had disappeared. In the cold-provocation test, before EA, the temperature recovery rates of mid fingertips after cold exposure reached over 80% in 20 min. In contrast, after EA had been completed, the temperature recovery rate exceeded 80% in 10 min, thus the delay of temperature recovery was alleviated. PMID- 20351381 TI - Efficacy of steroids or acupuncture for Bell's palsy. PMID- 20351384 TI - Drug-eluting stents versus bare-metal stents in acute ST-segment elevation myocardial infarction. a single-center experience with long-term follow up. AB - OBJECTIVES: To compare the efficacy and safety of drugeluting stents (DES) vs. bare-metal stents (BMS) in patients with acute ST-segment-elevation myocardial infarction (STEMI). BACKGROUND: DES effectively reduce restenosis in elective percutaneous coronary intervention. Limited data are available about the use of DES in patients with STEMI. METHODS: 453 consecutive patients who presented with STEMI between July 2003 and May 2006 were studied. The procedural characteristics, 30-day, 12-, 18- and 26-month outcomes of 277 patients treated with DES were compared with 176 patients treated with BMS. RESULTS: At 26-month follow up, DES therapy was associated with a significant decrease in major adverse cardiac events (MACE) (relative risk [RR] -35%; p = 0.01) and target lesion revascularization [TLR], RR -64%; p = 0.009). The DES group included more diabetic patients (20% vs. 9%; p < 0.001), and the stents were longer (22 +/- 0.28 mm vs. 19.4 +/- 0.36 mm; p < 0.001) and smaller (diameter: 2.9 +/- 0.02 mm vs. 3.1 +/- 0.02 mm; p < 0.001). The rate of stent thrombosis was similar and the prolonged combined antiplatelet therapy was an independent factor predicting a protective effect on MACE. CONCLUSIONS: DES reduce the incidence of TLR and MACE in patients with STEMI without evidence of additional risks at 2-year follow up. DES therapy was associated with more complex interventional techniques, which yielded similar procedural results and clinical outcomes that may be influenced by prolonged combined antiplatelet therapy. PMID- 20351385 TI - Drug-eluting stent versus bare-metal stent in acute ST-segment elevation myocardial infarction: a word of caution. PMID- 20351386 TI - Balloon aortic valvuloplasty for severe aortic stenosis as a bridge to high-risk transcatheter aortic valve implantation. AB - OBJECTIVES: To provide data on feasibility, safety and efficacy of balloon aortic valvuloplasty (BAV) as a bridge to transcatheter aortic valve implantation (TAVI). Background. There are no data on BAV use as a bridge to TAVI in patients at high risk of periprocedural complications. METHODS: Between June 2007 to May 2009, 83 consecutive patients with symptomatic severe aortic stenosis (48 female, 35 male) aged from 65 to 88 years (mean age 81 +/- 5 years) were treated with TAVI. Early hemodynamic and clinical outcomes of patients undergoing palliative BAV before TAVI (BAV Group, n = 43) were compared with those of patients who directly underwent TAVI (no-BAV Group, n = 40). RESULTS: Patients in the BAV group had worse baseline clinical characteristics than those in the no-BAV group, with higher rates of congestive heart failure, New York Heart Association (NYHA) functional class III or IV and a higher EuroSCORE. In the BAV group, significant changes were found after valvuloplasty with regard to NYHA functional class, mean pressure gradient and aortic valve area. Peak-to-peak transvalvular pressure gradient and left ventricular systolic pressure also decreased immediately after BAV. Before TAVI, no differences in either clinical status or hemodynamic data were observed between patients who underwent BAV and those who did not. CONCLUSIONS: Bridging to TAVI with BAV is a feasible and reasonably safe approach to offer temporary relief in selected high-risk patients with symptomatic severe aortic stenosis and a high chance of periprocedural complications. PMID- 20351387 TI - Racial difference in cardiovascular outcomes following percutaneous coronary intervention in a public health service patient population. AB - BACKGROUND: Prior studies have reported conflicting findings regarding racial disparities in long-term cardiovascular outcomes after percutaneous coronary intervention (PCI). Our aim was to compare major adverse cardiac events (MACE) following PCI in black versus non-black patients in a Public Health Service (PHS) setting. METHODS: A cohort of 1,438 consecutive patients undergoing intended PCI at a large public teaching hospital between April 2002 and September 2006 were followed for the development of MACE, defined as a composite of death, myocardial infarction (MI) and urgent target vessel revascularization. RESULTS: The study population consisted of 47.4% blacks, 21.3% whites, 15.2% Hispanics and 16.1% Asians. Overall, 17.4% of patients developed MACE over the mean followup period of 2.9 years. The rate of MACE was significantly higher in blacks compared with non-blacks (21.7% vs. 13.6%, log-rank p < 0.001). After adjusting for age, gender, cardiovascular risk factors, socioeconomic status (SES) and potential confounding factors, black race remained a strong and independent predictor of MACE (adjusted HR, 1.52; CI, 1.18-1.96; p = 0.001). Blacks had higher rates of death (12.3% vs. 5.2%, log-rank p < 0.001) and MI (8.7% vs. 4.4%, log rank p = 0.002). There were no racial differences in in-hospital mortality and 3-month and 6-month MACE. CONCLUSIONS: In this PHS population, blacks were found to have worse long-term cardiovascular outcomes and mortality following PCI, irrespective of differences in baseline cardiovascular risk factors, SES and health-care access. PMID- 20351388 TI - Vascular complications after percutaneous coronary intervention following hemostasis with the Mynx vascular closure device versus the AngioSeal vascular closure device. AB - We investigated the prevalence of vascular complications after PCI following hemostasis in 190 patients (67% men and 33% women, mean age 64 years) treated with the AngioSeal vascular closure device (St. Jude Medical, Austin, Texas) versus 238 patients (67% men and 33% women, mean age 64 years) treated with the Mynx vascular closure device (AccessClosure, Mountain View, California). RESULTS: Death, myocardial infarction or stroke occurred in none of the 190 patients (0%) treated with the AngioSeal versus none of 238 patients (0%) treated with the Mynx. Major vascular complications occurred in 4 of 190 patients (2.1%) treated with the AngioSeal versus 5 of 238 patients (2.1%) treated with the Mynx (p not significant). Major vascular complications in patients treated with the AngioSeal included removal of a malfunctioning device (1.1%), hemorrhage requiring intervention (0.5%) and hemorrhage with a loss of > 3g Hgb (0.5%). The major vascular complications in patients treated with the Mynx included retroperitoneal bleeding requiring surgical intervention (0.8%), pseudoaneurysm with surgical repair (0.8%) and hemorrhage with a loss of > 3g Hgb (0.4%). These complications were not significantly different between the two vascular closure devices (p = 0.77). Minor complications included hematoma > 5 cm (0.5%, n = 1) within the AngioSeal group, as well as procedure failure requiring > 30 minutes of manual compression after device deployment, which occurred in 7 out of 190 patients (3.7%) treated with the AngioSeal versus 22 of 238 patients with the Mynx (9.2%) (p = 0.033). CONCLUSIONS: Major vascular complications after PCI following hemostasis with vascular closure devices occurred in 2.1% of 190 patients treated with the AngioSeal vascular closure device versus 2.1% of 238 patients treated with the Mynx vascular closure device (p not significant). The Mynx vascular closure device appears to have a higher rate of device failure. PMID- 20351389 TI - Vascular closure devices--the other side of hemostasis. PMID- 20351390 TI - The Occlutech Figulla PFO and ASD occluder: a new nitinol wire mesh device for closure of atrial septal defects. AB - BACKGROUND: We investigated the safety, feasibility and efficacy of the Occlutech devices for patent foramen ovale (PFO) and atrial septal defect (ASD) closure in a prospective trial. METHODS: The retention discs of the PFO device (23 x 25 mm, 27 x 30 mm) are connected by a 3 mm waist in the center with only one right atrial side central pin. The left atrial disc is produced either with a single or double flat layer, which allows a significant reduction of meshwork material. The ASD occluder (6-40 mm, 3 mm increments) has only one central pin on the right atrial side. Indications for closure included cryptogenic stroke with evidence of a PFO on transesophageal echocardiography (TEE) or an ASD II. The devices were implanted in 29 patients with PFO and in 12 patients with ASD II (fluoroscopy and TEE). An echocardiographic follow-up examination was performed after 1, 2 and 6 months. RESULTS: The devices were successfully implanted in all 41 patients. There were no periprocedural complications. One patient with ASD II died of recurrent myocardial infarction without evidence of cardioembolic origin. TEE studies showed a residual shunt in 11.2% after 60 days in patients with PFO and a left-to-right shunt in 9.1% of the remaining patients with ASD II. After 180 days only 1 patient with PFO had a right-to-left shunt (3.7%). A residual shunt in the patients with ASD was not observed. CONCLUSIONS: The novel Occlutech devices appear to be safe, feasible and effective for PFO and ASD closure, with a significant reduction of the meshwork and absence of left atrial central pin. PMID- 20351391 TI - Quest for the ideal ASD/PFO closure device continues. PMID- 20351392 TI - Initial experience and sizing considerations using the three lobed amplatzer ductal occluder. AB - BACKGROUND: The recently released Amplatzer Ductal Occluder 2 (ADO2) was designed specifically for use in small children with moderate-sized shunts and larger children with small patent ductus arterioses (PDA). We report our initial experience with this device. METHODS: Patients referred with PDA underwent occlusion using the ADO2. This is a fabric-free nitinol wire 3-lobed device. All cases underwent pre-, intra- and post-procedural echocardiography, with follow up at 1 day and one month. Device sizing for device waist diameter and width was based on aortography. RESULTS: Seven patients with a median age of 3 years and 4 months (range 7 months-23 years) and a median weight of 12 kg (range 7-56 kg) underwent successful PDA closure. The median ductal diameter was 1.5 mm (range 0.4-4 mm). Both transpulmonary (6/7) and transaortic approaches (1/7) were used. Recurrent patency at 24 hours with complete occlusion at 1 month was noted in a single case. A specific device-based length assessment applied resulted in shorter than recommended device selection. CONCLUSION: The ADO2 broadens the spectrum of PDAs that can be simply and safely treated with devices. The flexibility of the articulations, coupled with the alternative deployment techniques, allow for increased ease of treatment in a range of small patients and specific ductal anatomies. An alternative device-specific length measurement of the duct length may result in less retaining disc protrusion. Broader experience is required to further delineate device and patient selection as well as to document its long-term efficacy and safety. PMID- 20351393 TI - Sinus of valsalva pseudoaneurysm and mechanical aortic valve endocarditis. AB - We present the case of a 54-year-old male with a St. Jude aortic valve replacement who presented with fever and a new diastolic murmur. An echocardiogram identified a pseudoaneurysm that appeared to originate from the left sinus of Valsalva. In anticipation of open valve surgery, a 64-slice computed tomographic (CT) angiogram was performed to characterize the size and location of the pseudoaneurysm. In addition, the CT scan was able to rule out significant coronary artery disease and obviate the need to perform a potentially high-risk catheterdirected angiogram in the setting of an infected pseudoaneurysm. PMID- 20351394 TI - Anomalous origin of right coronary artery from pulmonary artery and severe mitral regurgitation due to myxomatous mitral valve disease: a case report and literature review. AB - Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is an uncommon congenital coronary artery anomaly. In contrast to anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), most of the patients with ARCAPA remain asymptomatic. However, few cases of angina, heart failure and sudden cardiac death depicting the malignant nature of the disease are described in the literature. We report an unusual case of ARCAPA with severe mitral valve regurgitation and pulmonary hypertension. Echocardiography and angiography were utilized for the diagnosis. Surgical correction was provided to our patient and should be considered for all patients with this potentially fatal disease. PMID- 20351395 TI - Endoarterial scoring--a novel treatment for resistant pulmonary arterial lesions associated with Williams-Beuren syndrome. AB - A 7-year-old girl with Williams-Beuren syndrome had undergone multiple percutaneous interventions for resistant peripheral pulmonary arterial stenoses with primarily conventional high-pressure balloon dilatation, but also with use of a cutting balloon. On this occasion, we used the AngioSculpt (AngioScore, Alameda, California) to remodel her distal vessels bilaterally with good effect. We believe this to be the first report of its use in the pulmonary arterial circulation of man. PMID- 20351396 TI - Correction of CoreValve position using snare traction from a right brachial artery access. AB - Significant paravalvular aortic regurgitation is among the most important limitations of the interventional revalving techniques for the treatment of severe aortic stenosis. We report on the treatment of a patient with severe paravalvular regurgitation following CoreValve implantation by prolonged snare traction from the right brachial artery. Snare traction resulted in upward motion of the valve with subsequent reduction of aortic regurgitation from grades III/IV to grade I. PMID- 20351397 TI - Successful percutaneous endovascular management of acute post-traumatic superior mesenteric artery dissection using a transradial approach. AB - Acute aortic dissection extending into the superior mesenteric artery (SMA) following a blunt trauma is an extremely rare complication. We report a case of acute post-traumatic SMA dissection presented with an acute abdominal syndrome. Computed tomographic angiography and arteriography allowed a rapid diagnosis and urgent percutaneous endovascular intervention through transradial route. This approach saved a major surgical intervention and related morbidity. PMID- 20351398 TI - Retrograde approach to a totally occluded right coronary artery via a septal perforator artery: the tale of a long and winding wire. AB - Retrograde recannalization of chronic total occlusions has developed as a viable alternative to restore coronary patency. Techniques continue to evolve and complications described. We present a new complication related to equipment developed to improve outcomes via a retrograde approach. PMID- 20351399 TI - Coronary artery occlusion and myocardial infarction caused by vasospasm within a myocardial bridge. AB - Myocardial bridging is a common congenital coronary anomaly that is clinically silent in the majority of cases. Case reports suggest myocardial ischemia and infarction can be caused by myocardial bridging. The proposed mechanisms by which myocardial bridging causes myocardial ischemia include compromised coronary blood flow, endothelial dysfunction, thrombus formation and a strong association with coronary vasospasm. We reported a case of myocardial infarction caused by both myocardial bridging and coronary vasospasm. We reviewed the literature and suggest that coronary stenting may have a role in treating myocardial ischemia due to myocardial bridging and coronary spasm that is refractory to medical management. PMID- 20351402 TI - Theoretical study of physisorption of nucleobases on boron nitride nanotubes: a new class of hybrid nano-biomaterials. AB - We investigate the adsorption of the nucleic acid bases-adenine (A), guanine (G), cytosine (C), thymine (T) and uracil (U)-on the outer wall of a high curvature semiconducting single-walled boron nitride nanotube (BNNT) by first-principles density functional theory calculations. The calculated binding energy shows the order: G > A approximately C approximately T approximately U, implying that the interaction strength of the high curvature BNNT with the nucleobases, G being an exception, is nearly the same. A higher binding energy for the G-BNNT conjugate appears to result from hybridization of the molecular orbitals of G and the BNNT. A smaller energy gap predicted for the G-BNNT conjugate relative to that of the pristine BNNT may be useful in the application of this class of biofunctional materials to the design of next-generation sensing devices. PMID- 20351401 TI - Comment on' Superconducting transition in Nb nanowires fabricated using a focused ion beam'. AB - In a recent paper Tettamanzi et al (2009 Nanotechnology 20 465302) describe the fabrication of superconducting Nb nanowires using a focused-ion beam. They interpret their conductivity data in the framework of thermal and quantum phase slips below T(c). In the following we will argue that their analysis is inappropriate and incomplete, leading to contradictory results. Instead, we propose an interpretation of the data within an SN proximity model. PMID- 20351403 TI - Tin-oxide-coated single-walled carbon nanotube bundles supporting platinum electrocatalysts for direct ethanol fuel cells. AB - Novel tin-oxide (SnO(2))-coated single-walled carbon nanotube (SWNT) bundles supporting platinum (Pt) electrocatalysts for ethanol oxidation were developed for direct ethanol fuel cells. SnO(2)-coated SWNT (SnO(2)-SWNT) bundles were synthesized by a simple chemical-solution route. SnO(2)-SWNT bundles supporting Pt (Pt/SnO(2)-SWNTs) electrocatalysts and SWNT-supported Pt (Pt/SWNT) electrocatalysts were prepared by an ethylene glycol reduction method. The catalysts were physically characterized using TGA, XRD and TEM and electrochemically evaluated through cyclic voltammetry experiments. The Pt/SnO(2) SWNTs showed greatly enhanced electrocatalytic activity for ethanol oxidation in acid medium, compared to the Pt/SWNT. The optimal SnO(2) loading of Pt/SnO(2) SWNT catalysts with respect to specific catalytic activity for ethanol oxidation was also investigated. PMID- 20351400 TI - Impact papers on aging in 2009. AB - The Editorial Board of Aging reviews research papers published in 2009, which they believe have or will have significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacological interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically. PMID- 20351404 TI - Probing thermal expansion of graphene and modal dispersion at low-temperature using graphene nanoelectromechanical systems resonators. AB - We use suspended graphene electromechanical resonators to study the variation of resonant frequency as a function of temperature. Measuring the change in frequency resulting from a change in tension, from 300 to 30 K, allows us to extract information about the thermal expansion of monolayer graphene as a function of temperature, which is critical for strain engineering applications. We find that thermal expansion of graphene is negative for all temperatures between 300 and 30 K. We also study the dispersion, the variation of resonant frequency with DC gate voltage, of the electromechanical modes and find considerable tunability of resonant frequency, desirable for applications like mass sensing and RF signal processing at room temperature. With a lowering of temperature, we find that the positively dispersing electromechanical modes evolve into negatively dispersing ones. We quantitatively explain this crossover and discuss optimal electromechanical properties that are desirable for temperature-compensated sensors. PMID- 20351405 TI - Effects of transport gradients in a chemical vapor deposition reactor employing vapor-liquid-solid growth of ternary chalcogenide phase-change materials. AB - Chemical vapor deposition (CVD) with vapor-liquid-solid (VLS) growth is employed to synthesize individual Ge(2)Sb(2)Te(5) nanowires with the ultimate goal of synthesizing a large scale nanowire array for universal memory storage. A consistent challenge encountered during the synthesis is a lack of control over the composition and morphology across the growth substrate. To better understand the challenges associated with the CVD synthesis of the ternary chalcogenide, computational fluid dynamics simulations are performed to quantify 3D thermal and momentum transients in the growth conditions. While these gradients are qualitatively known to exist, they have not been adequately quantified in both the axial and radial directions when under pressure and flow conditions indicative of VLS growth. These data are not easily acquired by conventional means for the axial direction under vacuum and are a considerable challenge to accurately measure radially. The simulation data shown here provide 3D insights into the gradients which ultimately dictate the region of controllable stoichiometry and morphology. These results help explain the observed inhomogeneity of the characterized ternary chalcogenide growth products at various growth substrate locations. PMID- 20351407 TI - Nanowire transformation and annealing by Joule heating. AB - Joule heating of bundles of Mo(6)S(3)I(6) nanowires, in real time, was studied using in situ TEM probing. TEM imaging, electron diffraction, and conductivity measurements showed a complete transformation of Mo(6)S(3)I(6) into Mo via thermal decomposition. The resulting Mo nanowires had a conductivity that was 2-3 orders higher than the starting material. The conductivity increased even further, up to 1.8 x 10(6) S m( - 1), when the Mo nanowires went through annealing phases. These results suggest that Joule heating might be a general way to transform or anneal nanowires, pointing to applications such as metal nanowire fabrication, novel memory elements based on material transformation, or in situ improvement of field emitters. PMID- 20351408 TI - Microheater based on magnetic nanoparticle embedded PDMS. AB - A microheater was established by embedding magnetic nanoparticles into PDMS (MNP PDMS). MNP-PDMS generated heat under an AC magnetic field and the temperature was controlled by varying the magnetic particle content and the magnetic field intensity. In this study, the MNP-PDMS chip was demonstrated to amplify the target DNA (732 bp) with > 90% efficiency compared to the conventional PCR thermocycler, and exhibited good performance in regards to temperature control. This system holds great promise for reliably controlling the temperature of thermal processes on an integrated microchip platform for biochemical applications. PMID- 20351409 TI - Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials. AB - Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements. PMID- 20351410 TI - Nanoconfined surfactant templated electrodeposition to porous hierarchical nanowires and nanotubes. AB - Porous metal (Pd and Co) and semiconductor (ZnO) nanowires, porous metal (Pt and Ni) nanotubes, and unique multiple Pt nanowires are prepared from a novel nanoconfined surfactant templated electrodeposition approach. More specifically, the overall diameter of nanowires or nanotubes is defined by the pore channels of membranes. Surfactant assembled structure nanoconfined within the pores of membranes is used to generate the porosity and to control the texture of the nanowires or nanotubes. As compared to solid nanowires and nanotubes, the porous nanowires and nanotubes exhibit unique properties. For example, porous cobalt nanowires show higher coercivity. PMID- 20351411 TI - In-plane nanoelectromechanical resonators based on silicon nanowire piezoresistive detection. AB - We report an actuation/detection scheme with a top-down nanoelectromechanical system (NEMS) for frequency shift based sensing applications with outstanding performance. It relies on electrostatic actuation and piezoresistive nanowire gauges for in-plane motion transduction. The process fabrication is fully CMOS (complementary metal-oxide-semiconductor) compatible. The results show a very large dynamic range of more than 100 dB and an unprecedented signal to background ratio of 69 dB providing an improvement of two orders of magnitude in the detection efficiency presented in the state of the art in NEMS fields. Such a dynamic range results from both negligible 1/f noise and very low Johnson noise compared to the thermomechanical noise. This simple low power detection scheme paves the way for new class of robust mass resonant sensors. PMID- 20351412 TI - An optimized nanoparticle separator enabled by electron beam induced deposition. AB - Size-based separations technologies will inevitably benefit from advances in nanotechnology. Direct-write nanofabrication provides a useful mechanism for depositing/etching nanoscale elements in environments otherwise inaccessible to conventional nanofabrication techniques. Here, electron beam induced deposition was used to deposit an array of nanoscale features in a 3D environment with minimal material proximity effects outside the beam-interaction region. Specifically, the membrane component of a nanoparticle separator was fabricated by depositing a linear array of sharply tipped nanopillars, with a singular pitch, designed for sub-50 nm nanoparticle permeability. The nanopillar membrane was used in a dual capacity to control the flow of nanoparticles in the transaxial direction of the array while facilitating the sealing of the cellular sized compartment in the paraxial direction. An optimized growth recipe resulted which (1) maximized the growth efficiency of the membrane (which minimizes proximity effects) and (2) preserved the fidelity of the spacing between nanopillars (which maximizes the size-based gating quality of the membrane) while (3) maintaining sharp nanopillar apexes for impaling an optically transparent polymeric lid critical for device sealing. PMID- 20351413 TI - Position controlled nanowire growth through Au nanoparticles synthesized by galvanic reaction. AB - Semiconductor nanowires have emerged as promising materials for fundamental studies in quantum-confined systems and applications in nanophotonics and electronics, but major challenges remain in controlling nanowire properties, including their position and size. Here, we report a simple and efficient electrochemical process that combines galvanic reaction and electron-beam lithography to selectively synthesize gold nanoparticles that are consequently used for the growth of ordered GaAs nanowire arrays with pre-defined diameter and position. Size and density control of gold nanoparticles is achieved on non patterned GaAs substrates by changing the reaction time and concentration of Au(3 + ) ions during the galvanic reaction. Spontaneous formation of localized etch pits is observed when the galvanic reaction is constrained to lithography-defined substrate regions, which confines small-diameter Au nanoparticles during the high temperature growth of GaAs nanowire arrays and enables epitaxial growth of well ordered nanowire structures. PMID- 20351414 TI - Full-stream and part-stream ultrasound treatment effect on sludge anaerobic digestion. AB - The use of ultrasound as pre-treatment to improve anaerobic digestion of secondary sludge has been established as a promising technology. There are great differences between lab scale and full-scale devices, regarding the relationship between the disintegration achieved and the energy supplied. Based on economic aspects, most of the full-scale plants use partial-stream instead of the full stream sonication, which affects biogas production and digestate dewatering characteristics. A laboratory scale operation combining ultrasound and anaerobic digestion (batch tests) has been performed, determining the relationship between the ratio of sonicated sludge fed and the methane production, SCOD removal and capillary suction time after 20-day anaerobic biodegradation, in order to check the possible benefits of part-stream versus full-stream sonication. Additional incubation was also evaluated, searching for an optimum process combining ultrasound and 24-h incubation pretreatment. Results showed that by sonicating fresh WAS at 25,700 kJ/kg TS biogas yield increased linearly with the percentage of sonicated WAS in the substrate, from 248 (control reactor) to 349 mL CH(4)/g VS (41% increase in full-stream sonication). By incubation (24 h, 55 degrees C), 325 mL CH(4)/g VS were obtained (31% increase), but the digestion of the soluble compounds generated during incubation of sonicated sludge appeared to be less degradable compared to those solubilised by ultrasound or incubation alone, which showed no benefit in combining both treatments. Post-digestion dewatering deteriorated for both part-stream and full-stream sonication, and CST values were constant (74% higher than the control digestate) from 30% to 100% sonicated sludge. PMID- 20351415 TI - Pesticide runoff from greenhouse production. AB - A research has been undertaken studying pesticide residues in water from greenhouses and the use of soils and filter materials to reduce such losses. The pesticides detected in water samples collected downstream greenhouses include 9 fungicides, 5 herbicides and 4 insecticides. 10 compounds from flower and vegetable productions were frequently found to exceed environmental risk levels, and with a few exceptions the compounds were found in higher concentrations than those typically found in agricultural runoff. Some compounds were found in high concentrations (>1 microg/l) in undiluted runoff from greenhouses producing vegetables. Nutrient concentrations in the runoff were also sporadically very high, with phosphorous values varying between 0.85 and 7.4 mg P/l, and nitrogen values between 7.5 and 41.4 mg N/l. Undiluted runoff from the productions showed values of 60 mg P/l and 300 mg N/l. High values of pesticides correlated with high values of nutrients, especially P. Column experiments using a sandy agricultural soil and stock solutions of non-polar and slightly polar pesticides mixed with a complex binder and nutrients showed a significant reduction for nearly all of the compounds used, indicating that transport through soil will reduce the concentrations of the studied pesticides. The pesticide adsorption capacity of the filter materials pine bark, peat, Sphagnum moss, compost, oat straw, ferrous sand and clay soil were tested in batch and column experiments. Adsorption were studied contacting the filter materials with aqueous solutions containing greenhouse production pesticides. The batch experiments showed that pine bark and peat, both combining a high content of organic matter with a low ph, provided the highest adsorption for most of the tested pesticides. Sphagnum moss, compost and oat straw also showed high adsorption for most of the pesticides, while the mineral filters provided the lowest adsorption (30-55%). Further column experiments confirmed these results, displaying the best removal efficiency in the organic materials, varying from 200 microg/g in compost, to 500 microg/g in moss, straw and pine bark. PMID- 20351416 TI - Diversity of fecal coliforms and their antimicrobial resistance patterns in wastewater treatment model plant. AB - The occurrence of resistance patterns among wastewater fecal coliforms was determined in the study. Susceptibility of the isolates was tested against 19 antimicrobial agents: aminoglycosides, aztreonam, carbapenems, cephalosporines, beta-lactam/beta-lactamase inhibitors, penicillines, tetracycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. Additionally the removal of resistant isolates was evaluated in the laboratory-scale wastewater treatment model plant (M-WWTP), continuously supplied with the wastewater obtained from the full-scale WWTP. Number of fecal coliforms in raw (after mechanical treatment) and treated wastewater, as well as in aerobic chamber effluent was determined using selective medium. The selected strains were identified and examined for antibiotic resistance using Phoenix Automated Microbiology System (BD Biosciences, USA). The strains were identified as Escherichia coli (n=222), Klebsiella pneumoniae ssp. ozaenae (n=9), and Pantoea agglomerans (n=1). The isolate of P. agglomerans as well as 48% of E. coli isolates were sensitive to all antimicrobials tested. The most frequent resistance patterns were found for ampicillin: 100% of K. pneumoniae ssp. ozaenae and 41% of E. coli isolates. Among E. coli isolates 12% was regarded as multiple antimicrobial resistant (MAR). In the studied M-WWTP, the applied activated sludge processes reduced considerably the number of fecal coliforms, but increased the ratio of antimicrobial-resistant E. coli isolates to sensitive ones, especially among strains with MAR patterns. PMID- 20351417 TI - Fast start-up of a pilot-scale deammonification sequencing batch reactor from an activated sludge inoculum. AB - Deammonification involves the combined application of aerobic and anoxic ammonium oxidizing bacteria (AerAOB & AnAOB) and allows to treat wastewaters with a high ammonium concentration in a sustainable and cost-efficient way. So far, it could take more than one year to start up the process, even with the addition of AnAOB enriched inocula. In contrast, we started up a deammonifying reactor for the treatment of sludge digestate in less than four months without any AnAOB enriched inoculum. In a single sequencing batch reactor (SBR) of 3 m(3), nitritation and anammox were performed without nitrite accumulation. Larger biomass aggregates (>1.0 mm) had a typical reddish colour, but FISH also showed that small aggregates (<0.25 mm) contained a considerable amount of AnAOB. The AerAOB were related to Nitrosomonas halophila, N. eutropha and N. halophila, and the AnAOB to "Candidatus Kuenenia & Brocadia", as shown by FISH. Our results show that the deammonification inoculum does not play an important role, and that the AnAOB can quickly develop under the proper aerational conditions. Nitrogen was removed stably at high nitrogen loading rates (740 mg N/L/d) and removal efficiency (90%). PMID- 20351418 TI - Application of library-independent microbial source tracking methods for identifying the sources of faecal contamination in coastal areas. AB - Faecal contamination sources were identified in coastal areas around the Guerande Atlantique peninsula using two microbial source tracking (MST) methods: (i) Bacteroidales host-specific 16S rRNA gene markers measured by real-time PCR and (ii) F-specific bacteriophage (FRNAPH) genotyping. Both methods were used on 63 water samples from 7 water courses. HF183 marker and bacteriophage genogroup II (FRNAPH II) were detected in all water samples and in the majority of water samples, respectively, from La Torre stream (W5), Piriac (W2), R2000 (W3) and Mazy (W7) rain water drains, and also detected, less frequently, in Le Nau drain (W4), suggesting contamination by human faecal sources at these sites. These human markers were weakly detected in Pouliguen channel (W6). Furthermore, BacR and bacteriophage genogroup I (FRNAPH I) were also detected, but at lower concentration and frequency. So, site W6 seems to be contaminated by multiple sources, though mainly human. Finally, BacR was detected twice in Pont d'Armes channel (W1), whereas HF183 was not detected. FRNAPH I and II were detected in only 3 out of 12 water samples. Site W1 seems mainly contaminated by animal sources. As a result of our findings, actions were taken to remediate water and shellfish quality. PMID- 20351419 TI - Removal of arsenate from aqueous solution by nanocrystalline Mg/Al layered double hydroxide: sorption characteristics, prospects, and challenges. AB - Removal of arsenate (As(V)) from aqueous solution using both nanocrystalline and coprecipitated Mg/Al layered double hydroxides (LDHs) was examined under different sorption/desorption conditions. The surface area, pore volume, and pore size of the nanocrystalline LDH were significantly higher than those of the coprecipitated LDH, thus resulting in a higher As(V) sorption maximum than the coprecipitated LDH. The calculated activation energy (E(a)) value was 24.7 kJ/mol, suggesting the occurrence of anion exchange process for As(V) removal by the nanocrystalline LDH. The predominance of anion exchange process was further supported by the investigation of ionic strength effect, and XRD and FTIR analyses. The effect of aqueous matrix on As(V) sorption by the nanocrystalline LDH was found to increase in the order of nitrate < silica < sulfate < carbonate < phosphate. Regeneration study showed that a secondary sorption mechanism might occur concurrently for the As(V) sorption by nanocrystalline LDH besides the predominant anion exchange process. Prospects and challenges for practical application of the nanocrystalline LDH were also discussed in the latter part of this study. PMID- 20351420 TI - Modelling and experimental verification of a solar reactor for photo-Fenton treatment. AB - In the present work, a novel design of a solar reactor is presented. This pilot plant scale reactor uses the UV-Visible and Near-Infrared solar radiation to promote the photo-Fenton treatment. A theoretical study and experimental verification were performed using formic acid as a model pollutant. The radiative transfer, thermal energy and mass balances equations were solved to compute the formic acid (F) and hydrogen peroxide (P) concentrations as a function of time. The spectral and broadband solar radiation incident on the reactor window was calculated from a computational code: the SMARTS2 program. Statistical estimators have been used to measure the departure of theoretical model from experimental data. A good agreement for formic acid and hydrogen peroxide concentrations, temperature and total and UV broadband solar radiation was obtained. The normalized root mean square errors (NRMSE) of the model for predicted variables were lower than 11%. PMID- 20351421 TI - Regeneration of carbon nanotube and nanofibre composite film electrode for electrical removal of cupric ions. AB - Low cost and large scale carbon nanotube and nanofibre (CNT-CNF) composite films have been fabricated and employed as electrodes for electrosorption of cupric ions. The regeneration of the saturated CNT-CNF film electrode has been investigated. Three methods (short-circuiting, short-circuiting and then reversing voltage, reversing voltage and then short-circuiting) are used for regeneration. The results show that low regeneration efficiency of CNT-CNF film electrode due to electrodeposition of Cu on the electrode surface can be highly improved by regeneration applying reverse voltage combined with short circuit. 93% regeneration efficiency can be achieved when 0.8 V reverse voltage is applied before short-circuiting during regeneration of CNT-CNF film electrode. PMID- 20351422 TI - Feasibility of bioflocculation in a high-loaded membrane bioreactor for improved energy recovery from sewage. AB - The feasibility of a high-loaded membrane bioreactor to improve methane recovery from sewage was investigated. Although the process needs further optimization, it already is feasible to recover at least 35% of the sewage COD. Important aspects for further research are the occurrence of membrane fouling, and the optimum process conditions for bioflocculation, i.e. the proper SRT/HRT ratio, dissolved oxygen concentration and shear and overall energy production and consumption under optimised conditions. PMID- 20351423 TI - Evaluation of a hybrid upflow anaerobic sludge-filter bed reactor: effect of the proportion of packing medium on performance. AB - The aim of this study was to determine the effects of the volume occupied by the filter bed zone on the behavior of an anaerobic hybrid UASFB reactor. This configuration contains a sludge bed in the lower part of the reactor and a filter bed in the upper part. Three such reactors, each with a working volume of 9.8-L, were studied; these differed in proportion of packing medium occupying 50, 35 and 20% of the working volume of the reactors, respectively. All the reactors were fed with wine distillery vinasse and were operated for a period of 232 days at 33+/-1 degrees C with increasing OLRs. No significant differences were observed between the reactors for the range of OLRs studied. Indeed, relatively high OLRs could be reached for all the three reactors with an average OLR of about 18 g COD/L d towards the end of the experiment, while maintaining a constant HRT of 26 h. COD(t) and COD(s) removal efficiencies were always more than 80 and 86%, respectively, even for the highest OLR. High quantities of VS were accumulated in the reactors with an average value of 438+/-17 g per reactor. Most of the biomass was in the sludge bed zone suggesting that this part was playing a major role in COD removal. The internal packing medium on the top of the reactor had a key role in retaining the small flocculated particles inside the reactor, while minimizing the escape of solids in the effluent. This study suggests that low packing volume ratios can be used in the design of UASFB reactors, which allows a reduction in the costs of packing medium required as the supports are expensive. PMID- 20351424 TI - A pilot study of anaerobic membrane digesters for concurrent thickening and digestion of waste activated sludge (WAS). AB - The increased interest in biomass energy provides incentive for the development of efficient and high throughput digesters such as anaerobic membrane bioreactors (AnMBRs) to stabilize waste activated sludge (WAS). This paper presents the results of a pilot and short term filtration study that was conducted to assess the performance of AnMBRs when treating WAS at a 15 day hydraulic retention time (HRT) and 30 day sludge retention time (SRT) in comparison to two conventional digesters running at 15 (BSR-15) and 30 days (BSR-30) HRT/SRT. At steady state, the AnMBR digester showed a slightly higher volatile solids (VS) destruction of 48% in comparison to 44% and 35.3% for BSR-30 and BSR-15, respectively. The corresponding values of specific methane production were 0.32, 0.28 and 0.21 m(3) CH(4)/kg of VS fed. Stable membrane operation at an average flux of 40+/-3.6 LM( 2 )H(-1) (LMH) was observed when the digester was fed with a polymer-dosed thickened waste activated sludge (TWAS) and digester total suspended solids (TSS) concentrations were less than 15 gL(-1). Above this solids concentration a flux decline to 24.1+/-2.0 LM(-2) H(-1) was observed. Short term filtration tests conducted using sludge fractions of a 9.7 and 17.1 gL(-1) TSS sludge indicated 84 and 70% decline in filtration performance to be associated with the supernatant fraction of the sludge. At a higher sludge concentration, the introduction of unique fouling control strategy to tubular membranes, a relaxed mode of operation (i.e. 5 minutes permeation and 1 minute relaxation by) significantly increased the flux from 23.8+/-1.1 to 37.8+/-2.3 LMH for a neutral membrane and from 25.7+/ 1.1 to 44.9+/-2.9 LMH for a negatively charged membrane. The study clearly indicates that it is technically feasible to employ AnMBRs to achieve a substantial reduction in digester volumes. PMID- 20351425 TI - Modelling and simulation revealing mechanisms likely responsible for achieving the nitrite pathway through aeration control. AB - Nitrogen removal via nitrite has recently gained a lot of interest because it results in significant savings in both aeration costs and COD (chemical oxygen demand) requirements for denitrification, when compared to the conventional biological nitrogen removal via nitrate. The effectiveness of two different control strategies to achieve the nitrite pathway in systems with sludge retention has been experimentally demonstrated: (i) control of aerobic phase length, with which aeration is terminated as soon as ammonia is completely oxidised; (ii) operation at low DO setpoints in the aerobic phase. These strategies have been extensively studied in nitrifying reactors and are currently applied in real systems achieving biological carbon, nitrogen and phosphorus removal. In this work, we aim to demonstrate, through modelling and simulation, that the competition between nitrite reducers and nitrite oxidisers for nitrite, rather than kinetic selection plays a major role in NOB washout. Moreover, the results show that the occurrence of simultaneous nitrification and denitrification under "aerobic" conditions is very helpful for the nitrite pathway obtainment and for a more efficient COD utilisation. PMID- 20351426 TI - Water quality characteristics of Densu River basin in south-east Ghana. AB - Water quality of the Densu River was studied by determining the levels of various physico-chemical parameters including trace metals for planning of the basin. The pH range (7.40-8.22) fell within the natural background level 6.5-8.5. The river was moderately hard with high turbidity due to poor farming practices, which result in large quantities of topsoil ending up in the river after rains. The river waters were well oxygenated with a mean DO concentration of 6.3 mg/l. Nitrogen and phosphorus levels were below their natural background values. The Densu River showed an overall ionic dominance pattern of Na > Ca > K > Mg and Cl > HCO(3) > SO(4), a pattern which is an intermediate between fresh and sea water systems. The mean concentrations of metals for the basin followed the order: Fe > Mn > Zn > Pb > Cu > Cd. 84.6% of the sampling sites exceeded the background values of 0.3 mg/l and 0.1 mg/l for Fe and Mn respectively. Other metals Zn, Pb, Cu and Cd were all below their background levels indicating the river is unpolluted with respect to these metals. Water Quality index performed on the data depicted that River Densu is of poor to fairly good water quality. Regular water quality monitoring is recommended. PMID- 20351427 TI - Applying solubilization treatment to reverse clogging in laboratory-scale vertical flow constructed wetlands. AB - Substrate clogging is characterized as a frequently occurring operational problem for subsurface-flow constructed wetlands. The application of solubilization treatment to reduce clogging was tested in lab-scaled setups to provide a promising solution. The performance of solubilization treatment on reducing clogging and the related effects on plants and biofilms in the wetland system were investigated in this paper. The results showed that the infiltration rate and available porosity of wetland substrate increased as a function of increased dosage of NaOH, HCl, NaClO, and detergent, respectively. Among the four solvents, it appeared that NaClO had the most obvious effects on reducing clogging and the infiltration rate and effective porosity recovered to 69% of the original condition. The two possible reasons for solubilization were the flocculents' structure of the clogs was broken up or parts of the organic clogs were dissolved. The function of adding NaOH and NaClO was to dissolve the protein and polysaccharides of the organic clogs; the function of adding HCl was to release the anaerobic gas wrapped in the organic clogs. Furthermore, experiments results also showed that the solubilized solvents did not demonstrate a long-term negative effect on plants and biofilms. PMID- 20351428 TI - Wet hydrogen peroxide catalytic oxidation of phenol with FeAC (iron-embedded activated carbon) catalysts. AB - This investigation aims at exploring the catalytic oxidation activity of iron embedded activated carbon (FeAC) and the application for the degradation of phenol in the wet hydrogen peroxide catalytic oxidation (WHPCO). FeAC catalysts were prepared by pre-impregnating iron in coconut shell with various iron loadings in the range of 27.5 to 46.5% before they were activated. The FeAC catalysts were characterised by measuring their surface area, pore distribution, functional groups on the surface, and X-ray diffraction patterns. The effects of iron loading strongly inhibited the pore development of the catalyst but benefited the oxidation activity in WHPCO. It was found that the complete conversion of phenol was observed with all FeAC catalysts in oxidation. High level of chemical oxygen demand (COD) abatement can be achieved within the first 30 minutes of oxidation. The iron embedded in the activated carbon showed good performance in the degradation and mineralisation of phenol during the oxidation due to the active sites as iron oxides formed on the surface of the activated carbon. It was found that the embedding irons were presented in gamma-Fe(2)O(3), alpha-Fe(2)O(3), and alpha-FeCOOH forms on the activated carbon. The aging tests on FeAC catalysts showed less activity loss, and less iron leaching was found after four oxidation runs. PMID- 20351429 TI - A study on the relationship between BOD(5) and COD in a coastal seawater environment with a rapid BOD measurement system. AB - The dual objectives of this study are to: (1) examine the relationship between COD and BOD in seawater environment with a rapid but reliable method for the measurement of BOD in seawater, and (2) establish the relationship model between BOD(5) and COD in the firth of Dongbao River to predict the values of BOD(5). The first objective is met by the successful development of a technique utilizing bacteria-immobilized membrane flow cell for biodegradation process, coupled with fibre optic fluorescence detection for oxygen depletion quantitation. The technique has been applied to coastal seawater samples collected in the coastal area of Shenzhen, China. The BOD(5) and COD values for the samples are acquired and the results show that there is no apparent linear relationship existing between BOD(5) and COD in relatively clean seawater samples away from the shore. However, in estuary water samples containing relatively high concentration of sewage contamination, a linear correlation does exist between BOD(5) and COD. The linear relationship between the two parameters allows for the calculation of BOD(5) values based on COD data which can be measured more readily and precisely. PMID- 20351430 TI - Seasonal variations in the water quality, diversity and population ecology of intertidal macrofauna at an industrially influenced coast. AB - Present communication reports the physico-chemical and biological quality of seawater and status of benthos of a highly industrialized shore of the north western coastline of India. The coastal area considered for the present study, encircled by a variety of industries, was divided into two sampling sites and monitored for two consecutive years. Results of the water quality suggest that the obtained values of the physical and chemical parameters of seawater were comparable with data reported earlier. However, data obtained in the biological parameters of the seawater showed a declining trend. Results of the intertidal macrofaunal diversity studies revealed that the muddy upper littoral zones were represented by few species of coelenterata, porifera, arthropoda and mollusca. In the rocky-muddy middle littoral zones, gastropods, stars fishes, corallites, crabs, polychetes and tubeworms were present, whereas, predominantly rocky lower littoral zones were comparatively rich in macrofaunal diversity with small patches of coral colonies. However, when the results obtained in the present study was compared with that of earlier reported data, it was clear that the macrofaunal diversity indeed declined considerably over the years. This may be due to habitat destruction and habitat alteration in the coastline caused by increased anthropogenic activities in the area. Seasonal variations in the population density and abundance were observed in most of the faunal groups except in sessile corals and sponges. This may be due to local migration of the faunal groups towards deeper regions of the Gulf, as supported by the analysis of similarity, to avoid influx of freshwater during monsoon, and high temperature during summer and post monsoon seasons. The overall assessment of different parameters of this study revealed that though the physico- chemical characteristics of the seawater did not varied much from the earlier reported status, the biological characteristics of the seawater and intertidal zone was affected possibly by a high degree of anthropogenic pressure. PMID- 20351431 TI - Acceptability of the rainwater harvesting system to the slum dwellers of Dhaka City. AB - Urban area like Dhaka City, in Bangladesh, has scarcity of safe drinking water which is one of the prominent basic needs for human kind. This study explored the acceptability of harvested rainwater in a densely populated city like Dhaka, using a simple and low cost technology. A total of 200 random people from four slums of water-scarce Dhaka City were surveyed to determine the dwellers' perception on rainwater and its acceptability as a source of drinking water. The questionnaire was aimed at finding the socio-economic condition and the information on family housing, sanitation, health, existing water supply condition, knowledge about rainwater, willingness to accept rainwater as a drinking source etc. A Yield before Spillage (YBS) model was developed to know the actual rainwater availability and storage conditions which were used to justify the effective tank size. Cost-benefit analysis and feasibility analysis were performed using the survey results and the research findings. The survey result and overall study found that the low cost rainwater harvesting technique was acceptable to the slum dwellers as only the potential alternative source of safe drinking water. PMID- 20351432 TI - Vulnerability of freshwater resources in large and medium Nepalese river basins to environmental change. AB - This paper discusses vulnerability of freshwater resources in large and medium Nepalese river basins to environmental change based on evaluation of water resource availability and variation, resource development and use, ecological health and management capacity; and compares the situation with selected sub basins of the Ganges and the Mekong basins in Asia. Results suggest that water resources in the medium river basins are more vulnerable than in the large basins; and Nepalese basins, in general, are more vulnerable than other selected basins in the Asian region. The vulnerability in the Nepalese basins is more related to poor management capacity followed by resources variation and the least to development pressure. The poor management capacity is mainly related to low productivity of water use and the resources stress is related mainly to variation of the resource. PMID- 20351433 TI - Characteristics of nutrient retention in a stormwater wetland during dry and wet days. AB - A 0.23-ha pilot wetland was constructed to examine its effectiveness for the control of nonpoint source pollution (NPS) from a 7.42-ha agricultural watershed in Korea. The wetland was operated during base flow and storm flow conditions and monitored for four years (2006-2009). The wetland was operated under high hydraulic loading rates (HLRs, 0.78 m/day on average) during rainy days. The average influent nitrogen concentration was 9.8 mg/L during wet days, but around 11.6 mg/L during dry days. Due to the short hydraulic retention time (HRT) on wet days, nitrogen retention at the wetland was poor, only 6.1%; whereas, during dry days the efficiency was higher, around 17.9%. On rainy days, the wetland presented high retention for total phosphorus (TP), with an average efficiency of 68.3%, accompanied with a total suspended solids (TSS) removal of 84.7%. However, on dry days, the wetland showed positive soluble reactive phosphorus (SRP) retention other than TP. The interior of the wetland was observed to have different nutrients levels. Furthermore, suggestions are addressed in terms of improved design for better performance. PMID- 20351434 TI - Kinetic modelling of the photocatalytic inactivation of bacteria. AB - This work analyzes the kinetic modelling of the photocatalytic inactivation of E. coli in water using different types of kinetic models; from an empirical equation to an intrinsic kinetic model including explicit radiation absorption effects. Simple empirical equations lead to lower fitting errors, but require a total of 12 parameters to reproduce the results of four inactivation curves when the catalyst concentration was increased. Moreover, these parameters have no physical meaning and cannot be extrapolated to different experimental conditions. The use of a pseudo-mechanistic model based on a simplified reaction mechanism reduces the number of required kinetic parameters to 6, being the kinetic constant the only parameter that depends on the catalyst concentration. Finally, a simple modification of a kinetic model based on the intrinsic mechanism of photocatalytic reactions including explicit radiation absorption effects achieved the fitting of all the experiments with only three parameters. The main advantage of this approach is that the kinetic parameters estimated for the model become independent of the irradiation form, as well as the reactor size and its geometrical configuration, providing the necessary information for scaling-up and design of commercial-scale photoreactors for water disinfection. PMID- 20351435 TI - The effectiveness of humic acid coagulation with the use of cationic polyacrylamides. AB - The chemical coagulation process is a popular method for eliminating the precursors of disinfection by-products. This study presents the results of a laboratory experiment which investigates the use of cationic polyacrylamide copolymers (CPAMs) as primary coagulants in the purification of solutions containing humic acids (HA). A number of polymers with various molecular weight and charge density were tested. The optimal doses were determined by colloidal titration. The effectiveness of coagulation-flocculation was determined by jar test method. The post-coagulation suspension was separated by filtration through cellulose filter paper. The experiment showed that charge neutralization destabilizes organic colloidal particles. An inversely proportional relationship was observed between the optimal dose and polymer charge density. The effectiveness of UV(254) reduction (52-81%) and colour removal (51-88%) was determined by the effectiveness of filtration in removing post-coagulation turbidity, as well as by the type of applied polymer. The results of the study suggest that the use of CPAMs with high charge density and low molecular weight enables effective removal of humic acids from water in the coagulation and filtration process. PMID- 20351436 TI - Practical applications of quantitative microbial risk assessment (QMRA) for water safety plans. AB - The absence of indicator organisms in drinking water does not provide sufficient guarantee for microbial safety. Therefore the water utilities are implementing water safety plans (WSP) to safeguard drinking water quality. Quantitative microbial risk assessment (QMRA) can be used to provide objective quantitative input for the WSP. This study presents several applications of treatment modelling in QMRA to answer the risk managers questions raised in the WSP. QMRA can estimate how safe the water is, how much the safety varies and how certain the estimate of safety is. This can be used in the WSP system assessment to determine whether treatment is meeting health-based targets with the required level of certainty. Quantitative data analysis showed that short events of only 8 hours per year can dominate the yearly average health risk for the consumer. QMRA also helps the design of physical and microbial monitoring. The study showed that the required monitoring frequency increases with increasing treatment efficacy. Daily monitoring can be sufficient to verify a treatment process achieving 2 log reduction of pathogens, but a process achieving 4 log reduction needs to be monitored every 15 minutes. Similarly, QMRA helps to prepare adequate corrective actions by determining the acceptable 'down time' of a process. For example, for a process achieving 2.5 log reduction a down time of maximum 6 hours per year is acceptable. These applications illustrate how QMRA can contribute to efficient and effective management of microbial drinking water safety. PMID- 20351437 TI - A survey of the characteristics and maintenance of rainwater tanks in urban areas of South Australia. AB - Households resident in metropolitan Adelaide and surrounding areas in South Australia were recruited into a randomised controlled trial. A total of 630 rainwater tanks with a total tank capacity of 14.5 ML were installed at the 325 households surveyed. The majority of the tanks were plumbed into the kitchen (64.6%), over 10 years in age (45.5%), over 15,000 L in capacity (42.5%) and composed of galvanised steel (36.9%). Over 90% of the households undertook one or more prevention and maintenance strategies for reducing contamination of collected rainwater. The use of first flush diverters was reported by 30.8% households, the presence of leaf control devices on the tank by 57.2%, and the presence of leaf control screens on gutters by 25.5% households. Most households reported that the rainwater tank was cleaned at some time, with 50.4% of these households stating that tank cleaning occurred 1 to 5 years previously, and 31.9% more than 5 years prior to enrolment Rainwater from the main drinking tank was sampled from a subset of households for turbidity and metals (Al, Ca, Cu, Fe, Mg, Pb, Zn). This information regarding tank characteristics and degree of adherence to recommended maintenance procedures may assist understanding of variability in rainwater quality data and may help determine whether untreated rainwater can be considered a safe water supply for household purposes including drinking. PMID- 20351438 TI - Towards a low complexity carbon removal model for the optimal design of compact decentralised wastewater treatment systems. AB - On-site decentralised wastewater treatment systems can provide a financially attractive alternative to a sewer connection in locations far from existing sewer networks. Operational problems and shortcomings in the design of these systems still occur frequently. The aim of this paper is to provide a low complexity (i.e. easy to calibrate) but still accurate mathematical model that can be used to optimise the operational design of compact individual wastewater treatment systems. An integrated hydraulic and biological carbon removal model of a biofilm based compact decentralised treatment system is developed. The procedure for drafting the model is generic and can be used for similar types of wastewater treatment systems since (i) the hydraulic model is based on an N-tanks-in-series model inferred from tracer test experiments and (ii) (biofilm) respirometry experiments are exploited to determine the biodegradation kinetics of the biomass. Based on the preliminary validation results of the integrated model, the carbon removal in the system can be predicted quite accurately. While some adjustments could further improve the modelling strategy, the here presented results can already assist the manufacturers of compact treatment systems in efficiently (re)designing their systems. PMID- 20351439 TI - Monitoring and evaluation of removal of pathogens at municipal wastewater treatment plants. AB - The concentrations and removal of Cryptosporidium, Giardia, and microbial indicators, including somatic coliphages and fecal coliforms were investigated through the wastewater treatment processes at three municipal wastewater treatment plants in Beijing, China. The experimental results showed that the concentrations of Cryptosporidium in untreated wastewater, primary treatment effluent, secondary treatment effluent, tertiary treatment effluent were 33-600, 67-333, 0-9 and 0-0.4 oocysts L(-1), and that of Giardia were 130-3,600, 533 2,033, 0-32 and 0-2.1 cysts L(-1), respectively. The reduction ratios of Cryptosporidium and Giardia by the primary treatment process were 0.12 log and 0.18 log, respectively. Oxidation ditch process had higher reduction efficiency to Cryptosporidium and Giardia than anaerobic-anoxic-oxic process and conventional activated sludge process, probably because of longer retention time and higher sludge concentration. Membrane ultrafiltration had a notably better efficiency to reduce microorganisms, especially Cryptosporidium and Giardia, than conventional flocculation sedimentation and sand filtration process, as the tertiary treatment. Comparing with total coliforms, fecal coliforms and heterotrophic bacteria, concentration of somatic coliphages was correlated better with that of Cryptosporidium and Giardia in untreated wastewater and secondary treatment effluent. PMID- 20351440 TI - The simulation research of dissolved nitrogen and phosphorus non-point source pollution in Xiao-Jiang watershed of Three Gorges Reservoir area. AB - Xiao-jiang, with a basin area of almost 5,276 km(2) and a length of 182.4 km, is located in the center of the Three Gorges Reservoir Area, and is the largest tributary of the central section in Three Gorges Reservoir Area, farmland accounts for a large proportion of Xiao-jiang watershed, and the hilly cropland of purple soil is much of the farmland of the watershed. After the second phase of water storage in the Three Gorges Reservoir, the majority of sub-rivers in the reservoir area experienced eutrophication phenomenon frequently, and non-point source (NPS) pollution has become an important source of pollution in Xiao-jiang Watershed. Because dissolved nitrogen and phosphorus non-point source pollution are related to surface runoff and interflow, using climatic, topographic and land cover data from the internet and research institutes, the Semi-Distributed Land use Runoff Process (SLURP) hydrological model was introduced to simulate the complete hydrological cycle of the Xiao-jiang Watershed. Based on the SLURP distributed hydrological model, non-point source pollution annual output load models of land use and rural residents were respectively established. Therefore, using GIS technology, considering the losses of dissolved nitrogen and phosphorus in the course of transport, a dissolved non-point source pollution load dynamic model was established by the organic coupling of the SLURP hydrological model and land-use output model. Through the above dynamic model, the annual dissolved non point source nitrogen and phosphorus pollution output as well as the load in different types were simulated and quantitatively estimated from 2001 to 2008, furthermore, the loads of Xiao-jiang Watershed were calculated and expressed by temporal and spatial distribution in the Three Gorges Reservoir Area. The simulation results show that: the temporal changes of dissolved nitrogen and phosphorus load in the watershed are close to the inter-annual changes of rainfall runoff, and the different land-use type distribution has great impacts on the spatial changes of dissolved nitrogen and phosphorus load in the watershed; The nitrogen and phosphorus load of different land-use types in size with descending order is, glebe and mixed land, paddy, grassland, urban land, forestland; however, for the phosphorus load, the unit area output load of glebe and mixed land is almost the same as for paddy fields; The output contribution of nitrogen and phosphorus pollution load from land-use accounts for 78%-85%, while the output contribution from livestock and poultry occupies 13%-20%. The established load model was verified by observation data, simulation results show that the established model is reasonable, simulation accuracy is higher. PMID- 20351441 TI - Emission standards versus immission standards for assessing the impact of urban drainage on ephemeral receiving water bodies. AB - In the past, emission standard indicators have been adopted by environmental regulation authorities in order to preserve the quality of a receiving water body. Such indicators are based on the frequency or magnitude of a polluted discharge that may be continuous or intermittent. In order to properly maintain the quality of receiving waters, the Water Framework Directive, following the basic ideas of British Urban Pollution Manual, has been established. The Directive has overtaken the emission-standard concept, substituting it with the stream-standard concept that fixes discharge limits for each polluting substance depending on the self-depurative characteristics of receiving waters. Stream standard assessment requires the deployment of measurement campaigns that can be very expensive; furthermore, the measurement campaigns are usually not able to provide a link between the receiving water quality and the polluting sources. Therefore, it would be very useful to find a correlation between the quality status of the natural waters and the emission-based indicators. Thus, this study is aimed to finding a possible connection between the receiving water quality indicators drawn by environmental regulation authorities and emission-based indicators while considering both continuous (i.e. from the wastewater treatment plants) and intermittent pollution discharges (mainly from combined sewer overflows). Such research has been carried out by means of long-term analysis adopting a holistic modelling approach. The different parts of the integrated urban drainage system were modelled by a parsimonious integrated model. The analysis was applied to an ephemeral river bounding Bologna (Italy). The study concluded that the correlation between receiving water quality and polluting emissions cannot be generally stated. Nevertheless, specific analyses on polluting emissions were pointed out in the study highlighting cause-effect link between polluting sources and receiving water quality. PMID- 20351442 TI - Oxidation of cosmetic wastewaters with H(2)O(2) using a Fe/gamma-Al(2)O(3) catalyst. AB - A catalyst based on Fe supported on gamma-Al(2)O(3) has been prepared and tested for catalytic wet peroxide oxidation (CWPO) of cosmetic wastewaters. The influence of the main operating conditions (space-time, temperature, and H(2)O(2) dose) have been investigated. Working with this self-made Fe/gamma-Al(2)O(3) catalyst at 85 degrees C, with a space-time of 9.4 kg(cat) h/kg(COD) and a dose of H(2)O(2), corresponding to 0.5 times the theoretical stoichiometric H(2)O(2)/COD ratio, a substantial COD reduction (around 80%) has been reached with a complete consumption of H(2)O(2). The locally allowable limit of COD for industrial wastewaters discharge to the municipal sewer system can be achieved at lower temperature and space-time. The catalyst showed a high stability in 100 h time on stream tests, where COD and TOC reductions around 82 and 60%, respectively, were maintained working at 85 degrees C and 9.4 kg(cat) h/kg(COD) space-time. Fe leaching from the catalyst upon that time on stream was lower than 3% of the initial load. PMID- 20351443 TI - The use of qualitative system dynamics to identify sustainability characteristics of decentralized wastewater management alternatives. AB - In order to pursue more sustainable alternatives in wastewater management, it is vital that we understand how a given infrastructure alternative will impact the various aspects of sustainability. A set of qualitative tools (force field diagrams and causal loop diagrams (CLDs)) for the assessment of wastewater management alternatives is proposed and demonstrated in the context of a decentralized wastewater infrastructure upgrade. The objective for the application of these tools is to improve decision makers' understanding of how a given alternative will impact the economic, environmental/ecological, social, and functional aspects of sustainability. In the proposed method, each aspect of sustainability is treated as a stock, and its movement (up or down) can be inferred using both qualitative and quantitative data. By incorporating these tools into a participatory planning process, project-specific CLDs can be developed and loops of interest can be identified to help elucidate stakeholder values. The ultimate goal of this methodology is to facilitate the pursuit of sustainability in wastewater management by allowing decision makers to address specific sustainability challenges without creating new ones. PMID- 20351444 TI - Predicting responses from Rasch measures. AB - There is a growing family of Rasch models for polytomous observations. Selecting a suitable model for an existing dataset, estimating its parameters and evaluating its fit is now routine. Problems arise when the model parameters are to be estimated from the current data, but used to predict future data. In particular, ambiguities in the nature of the current data, or overfit of the model to the current dataset, may mean that better fit to the current data may lead to worse fit to future data. The predictive power of several Rasch and Rasch related models are discussed in the context of the Netflix Prize. Rasch-related models are proposed based on Singular Value Decomposition (SVD) and Boltzmann Machines. PMID- 20351445 TI - Concrete, abstract, formal, and systematic operations as observed in a "Piagetian" balance-beam task series. AB - We performed a Rasch analysis of cross-sectional developmental data gathered from children and adults who were presented with a task series derived from Inhelder's and Piaget's balance beam. The partial credit model situates both participants and items along a single hierarchically ordered dimension. As the Model of Hierarchical Complexity predicted, order of hierarchical complexity accurately predicted item difficulty, with notable exceptions at the formal and systematic levels. Gappiness between items was examined using the saltus model. A two level saltus model, which examined the gap between the concrete/abstract and formal/systematic items, was a better predictor of performance than the Rasch analysis (chi square = 71.91, df = 4, p < .01). PMID- 20351446 TI - Sources of self-efficacy belief: development and validation of two scales. AB - Self-efficacy belief has been an instrumental affective factor in predicting student behavior and achievement in academic settings. Although there is abundant literature on efficacy belief per se, the sources of efficacy belief have not been fully researched. Very few instruments exist to quantify the sources of efficacy-beliefs. To fill this void, we developed two scales for the two main sources of self-efficacy belief: past performance and social persuasion. Pilot test data were collected from 255 middle school students. A self-efficacy measure was also administered to the students as a criterion measure. The Rasch rating scale model was used to analyze the data. Information on item fit, item design, content validity, external validity, internal consistency, and person separation reliability was examined. The two scales displayed satisfactory psychometric properties. Applications and limitations of these two scales are also discussed. PMID- 20351447 TI - Reducible or irreducible? Mathematical reasoning and the ontological method. AB - Science is often described as nothing but the practice of measurement. This perspective follows from longstanding respect for the roles mathematics and quantification have played as media through which alternative hypotheses are evaluated and experience becomes better managed. Many figures in the history of science and psychology have contributed to what has been called the "quantitative imperative," the demand that fields of study employ number and mathematics even when they do not constitute the language in which investigators think together. But what makes an area of study scientific is, of course, not the mere use of number, but communities of investigators who share common mathematical languages for exchanging quantitative and quantitative value. Such languages require rigorous theoretical underpinning, a basis in data sufficient to the task, and instruments traceable to reference standard quantitative metrics. The values shared and exchanged by such communities typically involve the application of mathematical models that specify the sufficient and invariant relationships necessary for rigorous theorizing and instrument equating. The mathematical metaphysics of science are explored with the aim of connecting principles of quantitative measurement with the structures of sufficient reason. PMID- 20351448 TI - Children's understanding of area concepts: development, curriculum and educational achievement. AB - As one part of a series of studies undertaken to investigate the contribution of developmental attributes of learners to school learning, a representative sample of forty-two students (age from 5 years and 3 months to 13 years and 1 month) was randomly selected from a total student population of 142 students at a small private primary school in northern Australia. Those children's understandings of area concepts taught during the primary school years were assessed by their performance in two testing situations. The first consisted of a written classroom test of ability to solve area problems with items drawn directly from school texts, school examinations and other relevant curriculum documents. The second, which focused more directly on each child's cognitive development, was an individual interview for each child in which four "area" tasks such as the Meadows and Farmhouse Experiment taken from Chapter 11 of The Child's Conception of Geometry (Piaget, Inhelder and Szeminska, 1960, pp. 261-301) were administered. Analysis using the Rasch Partial Credit Model provided a finely detailed quantitative description of the developmental and learning progressions revealed in the data. It is evident that the school mathematics curriculum does not satisfactorily match the learner's developmental sequence at some key points. Moreover, the children's ability to conserve area on the Piagetian tasks, rather than other learner characteristics, such as age and school grade seems to be a precursor for complete success on the mathematical test of area. The discussion focuses on the assessment of developmental (and other) characteristics of school aged learners and suggests how curriculum and school organization might better capitalize on such information in the design and sequencing of learning experiences for school children. Some features unique to the Rasch family of measurement models are held to have special significance in elucidating the development/attainment nexus. PMID- 20351449 TI - Thinking about thinking - thinking about measurement: a Rasch analysis of recursive thinking. AB - Two studies were conducted to examine the dimensionality and hierarchical organization of a measure of recursive thinking. In Study 1, Rasch analysis supported the claim that the recursive thinking task measures a single underlying dimension. Item difficulty, however, appeared to be influenced not only by level of embeddedness but also by syntactic features. In Study 2, this hypothesis was tested by adding new items to the recursive thinking measure. Rasch analysis of the modified recursive thinking task produced evidence for the undimensionality and segmentation. However, Study 2 did not support the idea that syntactic features influence item difficulty. PMID- 20351450 TI - Psychometric aspects of item mapping for criterion-referenced interpretation and bookmark standard setting. AB - Locating an item on an achievement continuum (item mapping) is well-established in technical work for educational/psychological assessment. Applications of item mapping may be found in criterion-referenced (CR) testing (or scale anchoring, Beaton and Allen, 1992; Huynh, 1994, 1998a, 2000a, 2000b, 2006), computer assisted testing, test form assembly, and in standard setting methods based on ordered test booklets. These methods include the bookmark standard setting originally used for the CTB/TerraNova tests (Lewis, Mitzel, Green, and Patz, 1999), the item descriptor process (Ferrara, Perie, and Johnson, 2002) and a similar process described by Wang (2003) for multiple-choice licensure and certification examinations. While item response theory (IRT) models such as the Rasch and two-parameter logistic (2PL) models traditionally place a binary item at its location, Huynh has argued in the cited papers that such mapping may not be appropriate in selecting items for CR interpretation and scale anchoring. PMID- 20351451 TI - Antibiotic resistance in Mexico: a brief overview of the current status and its causes. AB - As in many other developing countries, conditions that may foster antibiotic resistance in Mexico differ from developed countries, and so resistance prevalence. Fecal pollution and other traits of overcrowded, poor cities, might create ideal settings for selecting, exchanging and maintaining resistance traits. Medical abuse of antibiotics, along with low-quality drugs, are also present as in many developing countries. Self-prescription, a common yet unmeasured practice among Mexican population, may also contribute to increased resistance rates. Pneumococcal resistance towards penicillin and macrolides are the highest in Latin American countries, as is resistance of Salmonella and uropathogenic Escherichia coli towards ampicillin and sulfamethoxazole trimethoprim; about one tenth of isolates of these gram-negative pathogens seem to produce extended-spectrum beta-lactamases (ESBL). High rates of multiple-drug resistant Mycobacterium tuberculosis are also found in Mexico, although there is no report of extensively drug-resistant strains. As to hospital-acquired pathogens, about a third of E. coli and Klebsiella isolates are ESBL-producers, and half of Staphylococcus aureus isolates are resistant to oxacillin (MRSA). Around 40% Pseudomonas aeruginosa isolates are resistant to ceftazidime, imipenem or levofloxacin. Although community-acquired MRSA, vancomycin-resistant enterococci, and other resistance problems found in developed countries, are not as common in Mexico, local issues are no small concern, and are disturbingly moving towards outpatients. PMID- 20351452 TI - High prevalence of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a tertiary care hospital in Tehran, Iran. AB - BACKGROUND: Extended-spectrum beta (beta)-lactamase (ESBL)-producing enterobacteria are major emerging pathogens in nosocomial infections. METHODOLOGY: The combination disk synergy test was used to evaluate 202 consecutive non-repeated Klebsiella pneumoniae (K. pneumonia) strains for ESBL production. The strains were isolated from various clinical specimens of hospitalized patients over the period from July 2005 to March 2007. Their antibiotic susceptibility pattern was also determined by the disk diffusion method. Demographic and medical data of the patients were recorded using a questionnaire. RESULTS: One hundred and fifty-seven (77.7%) of the isolates were confirmed as ESBL-producers. By univariate analysis, young age, stay in intensive care unit (ICU)/medical wards, recent stay in ICU, and number of days of ICU stay were found to be risk factors for acquisition of resistant bacteria (chi(2) and Mann-Whitney U tests, P < 0.05). However, binary logistic multivariate regression analysis confirmed that stay in ICU [Odds ratio (OR) 6.09, 95% confidence interval (CI) 2.36-15.72; P < 0.001] or medical wards [OR 3.72, 95% CI 1.42-9.75; P = 0.007] were significantly associated with ESBL production. Imipenem, ofloxacin, cefoxitin and norfloxacin (against urinary isolates) were found to be highly active against ESBL-producing isolates in vitro (100%, 75.2%, 69.4% and 66.7% susceptibility, respectively). In addition to most beta-lactams, they showed co-resistance with other antibiotics such as ciprofloxacin, aminoglycosides, trimethoprim/sulfamethoxazole and tetracycline. CONCLUSION: Our results showed a high prevalence of ESBL-producing K. pneumoniae in our hospital setting. As the available treatment options are limited, antibiotic control policies together with the implementation of infection control measures remain of high importance. PMID- 20351453 TI - Clinical and serological evaluation of Leptospirosis in Puducherry, India. AB - BACKGROUND: Leptospirosis is a zoonotic disease with a worldwide distribution. There is a paucity of available data about prevalence of this disease in Pondicherry. Our aim was to investigate the seropositivity rate of leptospirosis in suspected cases and also to identify the predominant serogroups present by performing Microscopic Agglutination Test (MAT). The other aim of this study was to compare the results of a commercially available IgM ELISA with that of MAT. METHODOLOGY: A total of 110 blood samples from patients suspected of leptospirosis were sent for diagnosis. These samples were subjected to IgM ELISA and the microscopic agglutination test (MAT). MAT was done using a panel of 12 Leptospira serovars. RESULTS: MAT analysis of the 110 samples showed 40 (36%) to be positive. Antibodies were predominantly seen against serogroup Leptospira Icterohemorrhagiae (27%), followed by Pomona (17%), and Pyrogenes (12%). IgM ELISA done on these samples showed a positivity of 37% compared to MAT. CONCLUSION: This study reveals that the MAT test can be standardized in a diagnostic laboratory and used in conjunction with an IgM ELISA. PMID- 20351454 TI - Prevalence of antibodies to human immunodeficiency virus (HIV), hepatitis B and hepatitis C and risk factors in prisoners in Lebanon. AB - BACKGROUND: People admitted to correctional facilities often have a history of risky behaviours which frequently lead to transmission of blood-borne viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our aim was to determine the prevalence of HIV, HBV and HCV infections among prisoners in Lebanon. METHODOLOGY: Conducted between August 2007 and February 2008 in Roumieh Prison, Lebanon, the study included a total of 580 male prisoners aged 16 and above who were randomly selected from four prison blocks. Peripheral blood was collected by a finger prick, blotted onto high quality filter paper, dried and later eluted to be tested for markers of HIV, HBV and HCV infections. RESULTS: A significantly higher seroprevalence of HBV (2.4%) and HCV (3.4%) was found among prisoners compared to the seroprevalence of these virus infections reported in the general Lebanese population (< 1% for HBV and HCV). Only one of the 580 prisoners tested (0.17%) was confirmed as anti-HIV positive. The majority (89%) of anti-HCV-positive prisoners had a history of previous imprisonment and were injecting drug users (IDUs). Tattooing was also associated with HCV transmission: all nine anti-HCV-positive prisoners had tattoos compared to only 60% who were anti-HCV-negative. Only HCV genotypes 1 and 3 were detected. CONCLUSIONS: We provide evidence for an outbreak of HCV and HBV occurring in Roumieh prison. In addition to vaccinating prisoners against HBV, collaborations should develop between the prison's administration, academic institutions, and community-based organizations to provide HCV prevention services within the prisons. PMID- 20351455 TI - Assessment of World Health Organization definition of dengue hemorrhagic fever in North India. AB - BACKGROUND: Classification of symptomatic dengue according to current World Health Organization (WHO) criteria is not straightforward. In this prospective study of dengue infection during an epidemic in India in 2004, we applied the WHO classification of dengue to assess its usefulness for our patients. METHODOLOGY: The study included 145 clinically suspected cases of dengue infection of all ages. Dengue was confirmed by serological methods (IgM ELISA and HI test). WHO criteria were applied to classify dengue positive patients into Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). Clinical and laboratory parameters were compared between dengue patients with bleeding and those without bleeding. RESULTS: Out of the 50 serologically positive cases of dengue enrolled in the study, only 3 met the WHO criteria for DHF and 1 met the criteria for DSS; however, 21 (42%) cases had one or more bleeding manifestations. CONCLUSION: By using WHO criteria of DHF on Indian patients, all severe cases of dengue cannot be correctly classified. A new definition of DHF that considers geographic and age-related variations in laboratory and clinical parameters is urgently required. PMID- 20351456 TI - Correlation of Trichomonas vaginalis to bacterial vaginosis: a laboratory-based study. AB - BACKGROUND: This study aimed to define the occurrence of different organisms causing vulvovaginitis; to evaluate different laboratory methods used for diagnosis of Trichomonas vaginalis (T. vaginalis); and to evaluate the direct score system and clue cell method compared with culture for diagnosis of bacterial and T. vaginalis vaginosis. METHODOLOGY: Clinical and laboratory evaluations were performed for 110 patients. Laboratory methods used for bacteriological diagnosis were direct Gram staining for clue cells and scoring by Nugent score system and bacterial culture. T. vaginalis was identified by wet mount microscopic examination, culture, direct Gram, Giemsa staining and acridine orange (AO). RESULTS: The Nugent score method revealed that the sensitivity and specificity for diagnosis of vaginal discharge by direct rapid microscopic methods were 30% and 80% and for clue cells sensitivity and specificity were 37% and 75% respectively for diagnosis of bacterial vaginosis compared to culture. For diagnosis of T. vaginalis, the Nugent score method revealed that the sensitivity and specificity were 60% and 90% respectively, and for clue cells 75% and 80% respectively. For microcopic methods used for T. vaginalis only, the Gram stain and Giemsa stain sensitivities were poor (15.2% and 48.5%, respectively). Wet mount showed reasonable sensitivity of 75.8%. Acridine orange sensitivity was 93.9% and specificity was 97.5%, CONCLUSION: Prevalent pathogens associated with vaginitis were (Gardnerella vaginalis) G. vaginalis, T. vaginalis and Mycoplasma hominis (M. hominis). Wet mount microscopic examination, acridine orange, and high Nugent score were found as rapid and sensitive methods for diagnosis of T. vaginalis. PMID- 20351457 TI - In vitro antimicrobials activity against endemic Acinetobacter baumannii multiresistant clones. AB - BACKGROUND: Multidrug-resistant strains of Acinetobacter baumannii have been reported increasingly around the world. The administration of an association of antibiotics has been proposed to create an active combination and to prevent the emergence of resistance. METHODOLOGY: The activity of colistin, rifampicin, gentamicin, imipenem and their associations was evaluated by means of killing curves in fourteen isolates belonging to three endemic PFGE types, in a university hospital of Buenos Aires city. The 14 isolates were selected on the basis of different mechanisms responsible for resistance to carbapenems and different susceptibility to colistin. RESULTS: The mechanism responsible for the resistance to imipenem was the production of OXA-23 and OXA-58 carbapenemases. Heteroresistance to colistin was observed in six isolates. The associations colistin-rifampicin and colistin-imipenem were synergistic in heteroresistant isolates and prevented the development of colistin-resistant mutants. The association imipenem-gentamicin was bactericidal in gentamicin susceptible isolates, whereas the association imipenem-rifampicin was always indifferent. CONCLUSION: The antimicrobial activity and the presence of synergy are related to the antimicrobials' susceptibilities irrespective of the PFGE type or the OXA carbapenemase produced. PMID- 20351458 TI - Maternal and neonatal seroprevalence of Hepatitis B surface antigen (HBsAg) in Tripoli, Libya. AB - BACKGROUND: Pregnant women with Hepatitis B virus HBV represent a major reservoir of the virus in the community. Data regarding the prevalence of HBV in pregnant women and maternal transmission of the virus in Libya are lacking. METHODOLOGY: Hepatitis blood samples from 1,500 pregnant women and 1,500 cord blood samples of their neonates delivered at Tripoli Medical Center, Tripoli, were tested for HBsAg by ELISA technique. HBsAg-positive samples were also tested for HBeAg. RESULTS: HBsAg was detected in 1.5% (23/1,500) pregnant women and in 0.9% (14/1,500) neonates. Although HBsAg was detected at higher rate in pregnant women aged > 25 years [1.8% (22/1,235)] than in pregnant women aged < 25 years [0.4% (1/265)], the difference was not statistically significant (P > 0.05). All HBsAg positive neonates were born to HBsAg-positive mothers with a rate of maternal transmission at 60.9% (14/23). HBeAg was detected in 21.7% (5/23) and in 7.1% (1/14) of HBsAg-positive pregnant women and neonates, respectively. CONCLUSIONS: Because of the high risk of developing chronic HBV infection at birth among infants born to HBsAg-positive mothers, administration of HBIG in combination with hepatitis B vaccine as post-exposure prophylaxis for such infants is of paramount importance. In addition, universal HBsAg screening of all pregnant women will greatly assist in reducing the maternal transmission of HBV in the country. PMID- 20351459 TI - Mycotic keratitis in India: a five-year retrospective study. AB - BACKGROUND: Mycotic keratitis is a fungal infection of the cornea. This infection is difficult to treat and it can lead to severe visual impairment or blindness. It is worldwide in distribution, but is more common in the tropics and subtropical regions. Trauma is the major predisposing factor, followed by ocular and systemic defects, prior application of corticosteroids, and prolonged use of antibiotic eye-drops. The objective of this study was to determine causative agents and to identify the predisposing factors of mycotic keratitis. METHODOLOGY: Corneal scrapings from 90 corneal ulcer patients with suspected fungal etiology were subjected to direct examination by 10% KOH mount, Gram stain and culture. RESULTS: This study included 90 subjects with corneal ulcers, based on clinical suspicion, of whom 41 cases were diagnosed with mycotic keratitis in the laboratory. Among these 41 cases, culture showed fungal growth only in 36 cases whereas the remaining five cases were positive only by potassium hydroxide (KOH) preparation. Males were more commonly affected and were mostly in the age group of 31-40 years. Aspergillus flavus was the most common fungus isolated followed by fusarium solani. CONCLUSION: Rapid diagnosis and early institution of antifungal therapy is necessary to prevent ocular morbidity and blindness. Although culture helps in definite diagnosis and identification, direct microscopic detection of fungal structures in corneal scrapes or biopsies permits a rapid presumptive diagnosis. PMID- 20351461 TI - Leptospirosis presenting as acute meningoencephalitis. AB - Leptospirosis in humans is a common zoonotic disease. It is often under diagnosed, especially when associated with neurological features, resulting in significant morbidity and mortality. This subgroup of patients with neurological manifestations is often empirically treated for cerebral malaria, dengue fever, tuberculous meningitis, hepatic encephalopathy, viral encephalitis, etc. Hence it is important to be aware of uncommon manifestations of this disease. We report one such patient, which highlights the importance of considering leptospirosis as the diagnostic possibility with hepato-renal, pulmonary and nervous system involvement, particularly where diagnostic supports and resources are limited. PMID- 20351460 TI - Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome. AB - Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl diagnosed LAD-I at the age of 7 years was brought to the Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, because of a draining plaque on the left leg for 2.5 years. She had recurrent skin infections and had been treated with repeated courses of different antibiotic combinations, with temporary responses, since 5 years of age. Examination revealed a 7 x 8 cm minimally erythematous hyperpigmented plaque with multiple draining sinuses on the left leg. Tissue culture yielded Pseudomonas aeruginosa. Flow cytometry showed CD18 (18.79%), CD11a (51.59%), CD11b (18.61%) and CD11c(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is highly suggested that patients diagnosed mild to moderate LAD-1 with recurrent skin infection and simultaneous weak response to conventional therapy undergo (BMT) marrow transplant to prohibit subsequent life-threatening complications. PMID- 20351462 TI - Omental cyst presenting as tubercular ascites. AB - Cystic lymphangiomas are uncommon congenital benign tumours of vascular origin with a lymphatic differentiation originating across various anatomical locations. Large intrabdominal cysts may mimic ascites. We report the case of a one-and-a half-year-old male child with a giant cystic lymphangioma originating in the greater omentum presenting as tubercular ascites. This report aims to highlight the limitations of biochemical investigations such as ascitic adenosine deaminase (ADA) in differentiating the epidemiologically prevalent tubercular ascites from an intrabdominal cyst, especially in a resource-poor nation as ours, where invasive diagnostic procedures pose an economic burden. PMID- 20351463 TI - Tungiasis infestation in Tanzania. AB - Tungiasis is caused by the jigger flea Tunga penetrans. We describe a case of severe infestation from Kigoma region, Western Tanzania. A 19-year-old male with epilepsy and mental disability presented with ulcerated and inflamed toes. Clinical examination revealed the presence of approximately 810 embedded jigger fleas on the feet, and another 60 lesions on the hands. The patient presented with fissures on the feet, hands and soles. He had difficulty walking and erythematous, oedematous, ulcerated and inflamed skin around the feet. Living conditions were precarious. The patient was assisted to extract the embedded fleas and his feet were washed with disinfectants. Oral antibiotics were given. The case shows that the disease may reach high parasite loads in Tanzanian individuals, with consequently severe pathology. There have been single reports of returning tourists from Tanzania with tungiasis, but the epidemiological situation and the geographic occurrence of the disease in this country are not known. Systematic studies are needed to increase knowledge on the epidemiological situation of tungasis in Tanzania and to identify endemic areas. PMID- 20351464 TI - Online resources on 2009 pandemic influenza for clinicians. AB - Numerous resources relevant to the 2009 pandemic influenza are available on-line . A casual search in google using the phrase "swine flu resources" yields 9,180,000 items making a time-bound search less fruitful for an average health care professional. This review has summarized the contents useful to practicing clinician available in 12 websites which were selected based on their relevance to clinical care. PMID- 20351465 TI - Inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulatory effect of human chorionic gonadotropin (HCG) and equine chorionic gonadotropin (ECG). AB - We examined the inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulating activity of human chorionic gonadotropin (HCG) and equine CG (ECG). Five TBAb positive sera obtained from patients who had been hypothyroid but were currently on T4 treatment. The TSH binding inhibitory immunoglobulin (TBII) activities of the sera were 60-160 IU/L. Inhibition of TSH binding to the TSH receptor (TSHR) [TSH binding inhibition (TBI) activity] of HCG or ECG, and inhibition of TBAb on HCG or ECG-stimulated cAMP production were examined. Both HCG and ECG preparations showed weak TBI activity in the presence of small amounts of protein [bovine serum albumin (BSA)] but were negative in the presence of large amounts of protein [normal human serum (NHS) or BSA]. Four thousand IU/mL of HCG and ECG preparation caused cAMP production similar to 100 microU/mL of bovine (b) TSH. The inhibitory effect of TBAb on cAMP production by this amount of HCG or ECG was then examined. The inhibitory effect of TBAb on cAMP production by HCG and ECG was similar to bTSH, and TBAb positive sera with more than 40 IU/L TBII activity completely blocked cAMP production by HCG, ECG and bTSH. This suggests that common alpha -subunit of both HCG and TSH are involved in the inhibitory effect of TBAb. Previous reports demonstrated that the thyroid stimulating activity of thyroid stimulating antibody (TSAb) was blocked by deglycosylated HCG (competitive antagonist of TSH binding to TSHR). The fact and our present study suggest that TSH, HCG ECG, TSAb and TBAb have a similar binding site (alpha-subunit-mimicking binding site) on the TSH receptor. PMID- 20351466 TI - The observation that risk increases according to the number of components does not necessarily indicate that each component is a risk factor. PMID- 20351467 TI - Relationship of the polyunsaturated to saturated fatty acid ratio to cardiovascular risk factors and metabolic syndrome in Japanese: the INTERLIPID study. AB - AIM: There have been few studies on the relationships of the dietary polyunsaturated to saturated fatty acid ratio (P/S) to cardiovascular risk factors and metabolic syndrome. We hypothesized that there would be favorable relationships. METHODS: Metabolic cardiovascular risk factors from dietary nutrient intake were investigated in 1,004 men and women aged 40-59 years from 4 population samples of Japanese. Multiple linear regression analysis was used to examine the relationship of the dietary P/S ratio to the following risk factors: hemoglobin A1c, blood pressure, serum triglycerides, LDL and total cholesterol, and HDL-cholesterol. Adjusted odds ratio of having metabolic syndrome was also calculated. RESULTS: The dietary P/S ratio was significantly and inversely related to serum total and LDL cholesterol with control for possible confounding variables. We did not find any significant relationship between the P/S ratio and single metabolic risk factors or the prevalence of metabolic syndrome. CONCLUSIONS: Managing the P/S ratio is important to control serum LDL cholesterol; however, increasing the P/S ratio may not improve metabolic risk factors. Other countermeasures, such as weight control, greater physical activity, and smoking cessation should be recommended to prevent and control metabolic syndrome. PMID- 20351468 TI - Fenofibrate reduces postprandial hypertriglyceridemia in CD36 knockout mice. AB - AIM: Metabolic syndrome (MetS) and postprandial hypertriglyceridemia (PHTG) are closely related and both are associated with coronary heart disease. We have demonstrated that CD36 deficiency is prevalent in the genetic background of MetS and is accompanied by PHTG concomitantly with an increase in remnants and a decrease in high density lipoprotein cholesterol. These findings make CD36 knockout mice (CD36KO) an interesting model for evaluating PHTG in MetS. Fenofibrate was reported to reduce fasting and postprandial triglyceride (TG) levels in hypertriglyceridemic subjects with MetS. To define its mechanism, we investigated the effect of fenofibrate on PHTG in CD36KO. METHODS: Wild-type (WT) and CD36KO mice were fed chow diet and fenofibrate for two weeks. TG concentrations and lipoprotein profiles were assessed during fasting and in the postprandial state in plasma; intestinal mucosa and lymph were collected after oral fat loading for both treatment groups. RESULTS: Fenofibrate treatment markedly suppressed the postprandial TG response in CD36KO along with decreased apoB-48 levels in plasma. HPLC analysis depicted the decrease of TG content in chylomicrons (CM) and CM remnant-sized lipoproteins contributed to this suppression, suggesting that CM and CM remnant production in the intestines might be attenuated by fenofibrate. ApoB-48 and TG levels in intestinal lymph were markedly reduced after treatment. Intestinal mRNA expression of apoB was also reduced in the postprandial state after fenofibrate administration without affecting any other genes related to CM assembly and production. CONCLUSION: Fenofibrate reduces PHTG in CD36KO partially through attenuating intestinal CM production. PMID- 20351469 TI - Regions of arterial stenosis and clinical factors determining transcutaneous oxygen tension in patients with peripheral arterial disease. AB - AIMS: Despite the clinical usefulness of transcutaneous oxygen tension (TcPO(2)) to assess the severity of limb ischemia, the factors determining TcPO(2) in patients with peripheral arterial disease (PAD) have not been fully clarified. We therefore examined the regions of arterial stenosis and clinical factors affecting lower-extremity TcPO(2). METHODS: Resting TcPO(2) (REST-TcPO(2)) and postexercise TcPO(2) (Ex-TcPO(2)) in the calf region and the dorsalis pedis were measured simultaneously in 66 patients (132 limbs) with clinically suspected PAD, in whom angiography was also performed. RESULTS: The peripheral arteries of the lower extremities were divided into five segments, and the impact of significant stenosis in each segment on ipsilateral TcPO(2) was evaluated by multiple regression analysis. In the calf region, significant stenosis of the proximal arteries (common-external iliac artery) revealed stronger involvement determining Ex-TcPO(2) than the peripheral segment (posterior tibial artery). In the dorsalis pedis, the peripheral segment (anterior tibial artery) more strongly determined Ex-TcPO(2) and REST-TcPO(2) than proximal segments. Age, creatinine, and diabetes were associated with REST-TcPO(2) of the calf region independent of arterial stenoses, while those of the dorsalis pedis were independently associated with age, and creatinine. In contrast, Ex-TcPO(2) in both regions was not independently associated with clinical factors, except for stenosis of the perfusing arteries. CONCLUSION: The vascular lesions affecting TcPO(2) differ between the calf region (proximal > peripheral) and the dorsalis pedis (proximal < peripheral). In addition postexercise TcPO(2) is solely determined by stenosis of the perfusing arteries, while TcPO(2) at rest is affected by multiple clinical factors. PMID- 20351471 TI - Integration of data from NIPPON DATA80/90 and National Nutrition Survey in Japan: for cohort studies of representative Japanese on nutrition. AB - BACKGROUND: Diet is one of the most important lifestyle factors that a affect healthy life expectancy through onset of various lifestyle-related diseases. Large-scale cohort studies with sufficient baseline nutritional information are scarce. NIPPON DATA80/90 is cohort study of representative Japanese population, and the cohorts also participated in the National Nutrition Survey in Japan (NNSJ) at the baseline. The corresponding datasets could be combined. METHODS: Individual records of NIPPON DATA and NNSJ were compared and integrated. Intakes of nutrients and food groups for individual participants were calculated by distributing intakes in the each household in NNSJ, considering age and sex of the individuals. The results from an international cooperative epidemiological study (INTERMAP) were utilized to estimate intakes of 75 nutrients for NNSJ80 and 70 nutrients for NNSJ90. Nutrient intakes calculated utilizing INTERMAP data were compared with those in the NNSJ datasets. RESULTS: NIPPON DATA80/90 datasets were enhanced with detailed baseline nutrient intake data (the numbers of participants combined were 10,422 and 8342 for NIPPON DATA80 and 90, respectively). The mean nutrient intakes calculated through utilizing INTEMRAP data and those calculated from the NNSJ datasets were similar, and the calculated values were strongly correlated with those calculated from NNSJ datasets (Pearson's correlation coefficients greater than 0.8 [P < 0.001]). Detailed nutrient intakes (eg, cholesterol, fatty acids, amino acids, and dietary fiber) were complemented. CONCLUSIONS: The nutrient intakes calculated from NNSJ datasets for the participants of NIPPON DATA are appropriate as the baseline nutrient intake data. The enhanced cohort datasets are suitable for investigations of baseline dietary habits and the consequent health status. PMID- 20351472 TI - Total energy intake and intake of three major nutrients by body mass index in Japan: NIPPON DATA80 and NIPPON DATA90. AB - BACKGROUND: This paper investigated the relationship between body mass index (BMI) and total energy intake as well as intake of three major nutrients in representative Japanese populations enrolled in the National Nutrition Surveys of Japan in 1980 and 1990. METHODS: A total of 10,422 participants (4585 men and 5837 women) and 8342 participants (3488 men and 4854 women) aged 30 or older from 300 randomly selected districts participated in the National Survey of Circulatory Disorders and the National Nutrition Survey in Japan in 1980 and 1990, respectively. The nutrition surveys were performed with weighing record method for three consecutive days to each household. Individually estimated total energy intake and intakes of three major nutrients (carbohydrate, protein, and fat) were compared by the categories of BMI and by 10-year age groups. RESULTS: In men, total energy intake (kcal/day), intakes of three major nutrients (g/day) and energy intake ratio from protein and fat (%) increased as BMI increased in each age group, whereas energy intake ratio from carbohydrate (%) decreased. In women, total energy intake, intakes of three major nutrients, and energy intake ratio from protein increased as BMI increased. Energy intake ratio from carbohydrate and fat decreased as BMI increased in women in 1990. When participants were categorized into quartiles according to total energy intake in each sex group, BMI increased as total energy intake increased in men in both 1980 and 1990. CONCLUSIONS: A positive relationship was observed between body mass index and total energy intake in Japanese men. The relationship was weaker in Japanese women. PMID- 20351473 TI - Dietary salt intake and blood pressure in a representative Japanese population: baseline analyses of NIPPON DATA80. AB - BACKGROUND: The relationship between dietary salt intake and blood pressure (BP) has been rarely investigated in a large population of Japanese. The characteristics of nutrients intake and foods intake in Japanese people with high salt intake have also not investigated well. METHODS: Data of 10,422 participants (4585 men and 5837 women) aged 30 or older who participated in both the National Survey on Circulatory Disorders and National Nutrition Survey in Japan conducted in 1980 were used. The nutrition surveys were performed with weighing record method for three consecutive days to each household. BP and intakes of nutrients and foods were compared by the quintiles of estimated individual salt intake per day. Analyses of covariance were used to calculate multivariate-adjusted mean BP values by the quintiles. RESULTS: Participants with higher salt intake showed higher intakes of soy beans/legume, fruit, other vegetables, and fish/shellfish. Intakes of protein, potassium, calcium, iron, magnesium, and fiber were higher in higher quintiles of salt intake. In men, adjusted systolic BPs were higher in the higher salt intake quintiles; there was 4.3 mm Hg difference in multivariate adjusted systolic BP between the lowest quintile (mean salt intake 8.7 g/day) and the highest quintile (mean salt intake 23.5 g/day) (P < 0.001). In women, adjusted mean systolic BPs were not statistically different among the quintile of salt intake. CONCLUSIONS: A positive relationship of dietary salt intake to BP was observed, especially in men, in this large-scale representative Japanese population. PMID- 20351474 TI - Protein intakes and serum albumin levels in a Japanese general population: NIPPON DATA90. AB - BACKGROUND: It is well-known that albumin is synthesized in the liver; serum albumin is a major component of serum proteins. However, it has not been well elucidated how dietary protein intakes are associated with serum albumin levels in general populations without extreme malnutrition. We cross-sectionally investigated in the representative Japanese the association between dietary protein intake and serum albumin levels. METHODS: A total of 7715 subjects (3220 men and 4495 women, aged 30 years or more) with measurement of serum albumin who participated in both the National Survey on Circulatory Disorders in 1990 and the National Nutrition Survey in 1990 were analyzed in the present analysis. Multiple adjustments were performed with linear regression models to estimate the association between serum albumin levels and animal or vegetable protein intake adjusting for age and body mass index. RESULTS: The very weak positive association between animal protein and serum albumin levels was observed. On the other hand, there was no clear association observed between vegetable protein and serum albumin levels. Regardless of sex and models, age was inversely associated with serum albumin levels with statistically significance, and standardized coefficients of age were considerably larger in both sexes than other variables. Adjustment for body mass index hardly altered the coefficients of animal or vegetable protein intake, but adjustment for total cholesterol clearly attenuated the relationship between animal protein intake and serum albumin levels. CONCLUSIONS: Present analysis indicated the possibility that animal protein intake was related with serum albumin levels, while vegetable protein intake was not related. PMID- 20351475 TI - Relationships between protein intake and renal function in a Japanese general population: NIPPON DATA90. AB - BACKGROUND: It has been considered that reducing protein intake is one of important measures to delay the progression of chronic kidney disease (CKD). However, the relationship between protein intake and renal function is still uncertain, especially in relatively healthy general population. METHODS: 7404 individuals (3099 men and 4305 women) who participated in both National Survey on Circulatory Disorders and National Nutrition Survey in 1990 and were free from past history of renal diseases were included in the present study. We estimated sex-specific age- and multivariate-adjusted glomerular filtration rate (GFR) and odds ratios for the presence of CKD according to the quartiles of protein (total, animal, vegetable) intake per body weight (kg). RESULTS: There were significant differences in each protein intake among the age groups in both men and women. Both participants with and without CKD took more protein intake than that of each recommended level. There were positive relationships between GFR and the quartiles of each protein intake in both sexes. The odds ratios for the presence of CKD were significantly decreased in the higher quartile of protein intake in women. CONCLUSIONS: The higher protein intake was associated with higher GFR in both sexes and low prevalence of CKD in women. However, further studies are needed to conclude the relationships between protein intake and renal function. PMID- 20351476 TI - Fatty acids intakes and serum lipid profiles: NIPPON DATA90 and the national nutrition monitoring. AB - BACKGROUND: The National Nutritional Survey in Japan (NNSJ) was initiated in 1946. Using the majority of the participants for NNSJ, the National Survey on Circulatory Disorders (NSCD) has been conducted every 10 year since 1960. We compared fatty acids intakes obtained from NNSJ and serum lipid profiles from NSCD conducted in 1990. METHODS: A total of 8344 community residents (4856 women and 3488 men, age > or = 30) from 300 randomly selected districts participated in the both surveys in 1990. At baseline, history, physical, and blood biochemical measurement and a nutritional survey were performed. We estimated nutrient intakes of each household member by dividing household intake data proportionally using average intakes by sex and age groups calculated for NNSJ95. RESULTS: Total fat, saturated fatty acids (SFA), poly-unsaturated fatty acids (PUFA), dietary cholesterol, and Keys dietary lipid factor (KEYS) were inversely associated with age in both men and women (all Ps < 0.001). In women, age and body mass index (BMI) adjusted serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc) were positively associated with SFA, total fat intakes (%kcal), and with KEYS (P < 0.001). In men, age-BMI adjusted HDLc was not associated with SFA, total fat intakes, and with KEYS factors unlike in women. Other associations were similar to those in women. CONCLUSIONS: The total fatty acids, SFA intakes, and KEYS lipid factor obtained from NNSJ were significantly associated with serum total and LDL cholesterol from the National Survey on Circulatory Disorders conducted in 1990. PMID- 20351477 TI - Calcium intake and associated factors in a general Japanese population: baseline data of NIPPON DATA80/90 and the National Nutrition Survey. AB - OBJECTIVE: The purpose of this study was to investigate the dietary calcium intake and associated other dietary factors among representative sample of Japanese general men and women. METHODS: Data was obtained by linking NIPPON DATA80 and 90 with the corresponding National Nutrition Surveys held in 1980 and 1990. We analyzed data for 10,422 subjects (4585 men and 5837 women) in NIPPON DATA80 and 8342 subjects (3488 men and 4854 women) in NIPPON DATA90. Calcium intake was calculated by age groups. Dietary calcium intake was classified into quintiles and physical, life-style, and dietary parameters were examined across the quintiles. RESULTS: For both men and women, calcium intake tended to be positively associated with age in NIPPON DATA80 and 90, and there were significant differences in estimated calcium intake between age groups. Calcium intake tended to be positively associated with age, protein, fat, saturated fat, vitamins A and C, sodium, potassium, and iron for men and women. Calcium intake also tended to be positively associated with intake of nuts, potatoes, sugar and sweeteners, soybeans and legumes, fruits, green and yellow vegetables, other vegetables, mushrooms, sea algae, fish and shellfish, eggs, and milk and dairy products for men and women. CONCLUSIONS: The characteristics of calcium intake in Japanese people were able to be clarified by using the baseline data of NIPPON DATA and the National Nutrition Survey. PMID- 20351478 TI - Iron intake and associated factors in general Japanese population: NIPPON DATA80, NIPPON DATA90 and national nutrition monitoring. AB - OBJECTIVE: The purpose of this study was to investigate the dietary iron intake and associated other dietary factors and clinical characteristics among a representative sample cohort of Japanese population. METHODS: We obtained data from NIPPON DATA80 and 90 that were conducted with the National Nutrition Surveys in 1980 and in 1990. Then we estimated nutrient and food intakes of individuals in the National Nutrition Survey of 1980 and that of 1990, which were adjusted on the basis of data of the National Nutrition Survey of 1995. Finally, we analyzed data for the 10,422 participants (4585 men and 5837 women) in NIPPON DATA80 and 8342 participants (3488 men and 4854 women) in NIPPON DATA90 having dietary iron intake information. RESULTS: In NIPPON DATA80 and 90, there was a significant relationship between the dietary iron intake and age for both men and women. Dietary protein intake was associated with iron intake where as dietary fat intake did not show any association. Regarding the minerals, significant relationships were observed between the different minerals and dietary iron intake. Apart from the food group of milk and dairy products, there were significant differences in other food groups according to quintiles of iron intakes for men and women. CONCLUSIONS: We described the mean dietary iron intake and its relation with other dietary factors and clinical characteristics in Japanese adults as the baseline data in NIPPON DATA80 and in NIPPON DATA90. PMID- 20351479 TI - Dietary intake of potassium and associated dietary factors among representative samples of Japanese general population: NIPPON DATA 80/90. AB - OBJECTIVE: The purpose of this study was to investigate the dietary potassium intake and associated other dietary factors among a representative sample cohort of Japanese population. METHODS: We obtained data from NIPPON DATA80 and 90 that were conducted with the National Nutrition Surveys in 1980 and in 1990. Then we estimated nutrient and food intakes of individuals in the National Nutrition Survey of 1980 and that of 1990, which were adjusted on the basis of data of the National Nutrition Survey of 1995. We analyzed data for 10,422 participants (4585 men and 5837 women) in NIPPON DATA80 and 8342 participants (3488 men and 4854 women) in NIPPON DATA90 having dietary potassium intake information. RESULTS: In NIPPON DATA80 and 90 it was observed that there was a significant relationship between the dietary potassium intake and age for both men and women. Higher potassium intake was associated with higher age, intake of protein, iron, calcium, sodium, vitamins, and fiber. Regarding food groups, lower amount of dietary cereals, rice, flour, fats and oils were associated with higher dietary potassium for both men and women. On the other hand, higher intake of nuts, potatoes, soy beans, fruits, vegetables, mushrooms, sea algae, fish and shellfish were associated with higher dietary potassium. CONCLUSIONS: We obtained the mean dietary potassium intake and its association with other dietary nutrient intake in Japanese adults as the baseline data in NIPPON DATA80 and in NIPPON DATA90. PMID- 20351480 TI - Association between food group intake and serum total cholesterol in the Japanese population: NIPPON DATA 80/90. AB - BACKGROUND: Dietary habit is one of the important determinants of health. Investigation of the association between diet and blood lipids at the food product level is more advantageous than that at the nutrient level because the results can be applied more directly to improving dietary habits for disease prevention. METHODS: The integrated datasets of the NIPPON DATA and National Nutrition Surveys in Japan conducted in 1980 and 1990 were used for analysis. The association between serum total cholesterol concentration and food group intake was examined by multiple linear regression analysis separately for sex and survey year with data adjusted for age, body mass index and total energy intake. RESULTS: Intakes of rice, sugar, sweets and snacks, fruit and vegetables other than green and yellow ones were lower and intakes of green and yellow vegetables, mushrooms, seaweed, eggs and milk were higher in the 1990 survey than in the 1980 survey. Intakes of meat, milk and eggs showed a positive association with serum total cholesterol concentration in both sexes while intake of legumes showed a negative association only in men in both the 1980 and 1990 surveys. CONCLUSIONS: Sex- and age-specific food group intakes for 1980 and 1990 were identified, and positive and negative associations between serum total cholesterol concentration and food group intake were revealed in a representative sample of the Japanese population. The results provide some insights into the improvements in dietary habits that can be made for disease prevention in Japan. PMID- 20351481 TI - Comparison of the National Nutritional Survey in Japan estimated individual-based nutritional data and NIPPON DATA80 food frequency questionnaires. AB - BACKGROUND: The National Nutritional Survey in Japan (NNSJ) was initiated in 1946. Using the majority of the participants for NNSJ, the National Survey on Circulatory Disorders has been conducted every 10 year since 1960. We performed a comparative study of the NNSJ80 estimated individual-based nutritional data by comparing those with NIPPON DATA80 food frequency questionnaires (FFQ) data. METHODS: A total of 10 546 community residents from 300 randomly selected districts participated in the both surveys in 1980. At baseline, history, physical, and blood biochemical measurement and a nutritional survey by FFQ were performed individually. From household-based NNSJ80 data, we estimated nutrient intakes of each household member by dividing household intake data proportionally using average intakes by sex and age groups calculated for NNSJ95. We re categorized NNSJ80 estimated data to correspond to NIPPON DATA80 FFQ categories. Data were analyzed in men and women separately. RESULTS: Cross tables showed fairly good agreement of the two categories. The majorities of participants situated on the diagonally aligned cells or the next to them. Weighted kappa ranged from 0.152 to 0.241. Spearman's rank correlation coefficients between the two categories ranged from 0.224 to 0.338, and those between NNSJ80 continuous data and NIPPON DATA80 categorical data ranged from 0.237 to 0.354. All these values have P < 0.001. CONCLUSIONS: These results may indicate that the present nutritional estimation method is applicable to, further studies. PMID- 20351483 TI - Some embryological aspects of cholinergic innervation in the cardiovascular system--a close association with the subintestinal circulatory channel. AB - A series of our studies on the dog venous system revealed that cholinergic excitatory innervation was localized in a group of veins: the portal, mesenteric, and hepatic veins and the middle segment of the inferior vena cava. Our studies on pharmacological responsiveness of dog veins also revealed that they could be divided into two groups: the visceral and somatic parts, and the cholinergic excitatory innervation localized to the visceral part. Considering these results and some relevant literature, a hypothesis is proposed on the classification of muscles of the cardiovascular system and some embryological aspects of the parasympathetic cholinergic innervation in the circulatory system are discussed. The embryonic circulatory system of vertebrates can be divided into two parts: somatic and visceral. The body of an embryo is regarded as a double tube and vessels of the visceral part and the heart belong to the inner tube. The muscle of these vessels and the heart are derived from visceral mesoderm, either the coelomic epithelium or mesenchymal cells, in common with muscle of the digestive tube; and thus the parasympathetic cholinergic nerves innervating the muscle of the digestive tube also distribute to these vessels and the heart. The heart and vascular muscles in the visceral part are structures developed early in the course of evolution in invertebrates. Their primary function is to propel the body fluid, and the chief structure containing them is the subintestinal circulatory channel (ventral aorta - heart - subintestinal vein). They exhibit spontaneous, rhythmic activity, showing characteristics of a single unit muscle, and receive parasympathetic cholinergic innervation. On the other hand, the vascular muscles in the somatic part are endothelium-associated muscles developed anew in the vertebrate; do not contract spontaneously, being classified as a multiunit muscle; and lack parasympathetic cholinergic innervation. PMID- 20351484 TI - Tarantula toxin ProTx-I differentiates between human T-type voltage-gated Ca2+ Channels Cav3.1 and Cav3.2. AB - ProTx-I peptide, a venom toxin of the tarantula Thrixopelma pruriens, has been reported to interact with voltage-gated ion channels. ProTx-I reduced Ba(2+) currents through recombinant human T-type voltage-gated Ca(2+) channels, Ca(v)3.1 (hCa(v)3.1), with roughly 160-fold more potency than through hCa(v)3.2 channels. Chimeric channel proteins (hCa(v)3.1/S3S4 and hCa(v)3.2/S3S4) were produced by exchanging fourteen amino acids in the hCa(v)3.1 domain IV S3-S4 linker region and the corresponding region of hCa(v)3.2 between each other. The ProTx-I sensitivity was markedly reduced in the hCa(v)3.1/S3S4 chimera as compared to the original hCa(v)3.1 channel, while the hCa(v)3.2/S3S4 chimera exhibited greater ProTx-I sensitivity than the original hCa(v)3.2 channel. These results suggest that the domain IV S3-S4 linker in the hCa(v)3.1 channel may contain residues involved in the interaction of ProTx-I with T-type Ca(2+) channels. PMID- 20351485 TI - Local administration of a synthetic cell-penetrating peptide antagonizing TrkA function suppresses inflammatory pain in rats. AB - Novel agents that inhibit nerve growth factor signaling are required for the treatment of inflammatory pain. The present study investigated the effect of local administration of inhibitory peptide of TrkA (IPTRK3), a synthetic cell penetrating peptide that antagonizes TrkA function, in complete Freund's adjuvant (CFA)-induced hyperalgesia in rats. Three hours after subcutaneous injection of CFA into the plantar surface of the rat's left hind paw, 10 mM IPTRK3 was injected at the same site. Thermal and mechanical hyperalgesia were tested in the ipsilateral hind paw until 7 days after CFA injection. The ipsilateral dorsal root ganglion (DRG) was dissected out for immunohistochemical analysis of transient receptor potential vanilloid subfamily member 1 (TRPV1) channels and TrkA. Local injection of this peptide significantly suppressed both thermal and mechanical hyperalgesia produced by CFA and also significantly reduced TRPV1 expression at the DRG. These results suggest that local administration of IPTRK3 is likely effective in the treatment of inflammatory pain in rats. PMID- 20351486 TI - Effects of SA13353, a transient receptor potential vanilloid 1 agonist, on leukocyte infiltration in lipopolysaccharide-induced acute lung injury and ovalbumin-induced allergic airway inflammation. AB - We recently demonstrated that SA13353, a transient receptor potential vanilloid 1 (TRPV1) agonist, reduced the severity of the symptoms of kidney injury, arthritis, and encephalomyelitis in disease models. Here, we investigated the effects of orally administered SA13353 on leukocyte infiltration in lipopolysaccharide (LPS)-induced acute lung injury and ovalbumin-induced allergic airway inflammation. In LPS-induced lung injury, SA13353 attenuated neutrophil infiltration and the increase of TNF-alpha and CINC-1 levels. In allergic airway inflammation, SA13353 tended to inhibit leukocyte infiltration and attenuated the increase of IL-4 and IL-12p40. These results suggest that somatosensory TRPV1 may play an anti-inflammatory role in lung inflammation. PMID- 20351487 TI - Sclerosing mesenteritis involving the pancreas: a mimicker of pancreatic cancer. AB - Sclerosing mesenteritis (SM), also known as mesenteric lipodystrophy, rarely involves the parenchyma of the pancreas. When SM does involve the pancreas, it can mimic pancreatic carcinoma both clinically and radiographically with pain, obstructive jaundice, a mass lesion, and even the appearance of vascular invasion. We report 6 patients with SM involving the pancreas (mean age 43.2 y, 5 female), and review their clinical presentation, radiographic findings, pathology, and outcome. Five of these 6 patients were originally thought to have a primary pancreatic neoplasm. Initial presenting clinical information was available for each patient: all 6 reported abdominal or epigastric pain, 3 reported weight loss, and 2 reported one or more of the following: back pain, fever, abdominal bloating/distention, nausea with/without vomiting, and anorexia. The lesions formed masses with an infiltrative pattern and all had 3 key histologic features: fibrosis, chronic inflammation, and fat necrosis-without a known etiology. The inflammatory infiltrate was composed of a mixture of lymphocytes, plasma cells, and scattered eosinophils. Of the 5 patients with post treatment clinical information available, 4 had at least a partial response to treatment with steroids, tamoxifen, azathioprine, resection, or a combination of these, and 1 did not respond. A dramatic response to immunosuppressive therapy is illustrated by the case of a 46-year-old woman who presented with the presumptive diagnosis of an unresectable pancreatic cancer. Distinguishing SM from pancreatic carcinoma is crucial to appropriate management, as patients with SM may benefit from immunosuppressive therapy. PMID- 20351488 TI - CD61, CD31, and CD34 improve diagnostic accuracy in gastric antral vascular ectasia and portal hypertensive gastropathy: An immunohistochemical and digital morphometric study. AB - Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are unusual but important causes of gastrointestinal bleeding with characteristic endoscopic appearances and critically different therapies. However, overlapping features and poor endoscopic-histologic correlation make their distinction challenging. We sought to determine whether CD31, CD34 (vascular markers), and CD61 (platelet marker) could aid in their differentiation. Cases included 11 antral specimens with histologic diagnoses of GAVE, 11 histologically diagnosed as PHG, and biopsies of GAVE (15) or PHG (12) suspected on endoscopy but without histologic agreement. Controls consisted of endoscopically and histologically normal antrum. Image analysis of CD31 and CD34-stained sections was performed to determine mucosal microvessel density (MVD). CD61 revealed thrombi in 100% of histologically confirmed cases of GAVE and 60% of cases suspected of GAVE on endoscopy alone; control biopsies were negative. CD61 was also positive in 26% of cases originally signed out as PHG. Review of hematoxylin and eosin slides from these CD61-positive PHG cases showed other features allowing their correct reclassification as GAVE. MVD was significantly higher in GAVE than PHG. MVD in histologically confirmed PHG did not differ significantly from endoscopically suspected PHG. Review of hematoxylin and eosin slides from the latter showed active gastritis obscuring recognition of ectatic vessels. In conclusion, CD61 reliably differentiates GAVE from PHG. MVD analysis can also assist in their distinction. In PHG, the increased vascularity may be subtle in an inflammatory background; vascular markers may serve as adjunct markers for identifying the aberrant vessels. PMID- 20351489 TI - Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases. AB - Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or histologically mature teratoma. However, lesions with the morphology of atypical carcinoid can occasionally exhibit metastatic spread. PMID- 20351490 TI - Biopsy findings in acute pulmonary histoplasmosis: unusual histologic features in 4 cases mimicking lymphomatoid granulomatosis. AB - Most examples of pulmonary histoplasmosis, including histoplasmoma and chronic histoplasmosis, are characterized by typical necrotizing granulomatous inflammation. Only disseminated histoplasmosis is recognized as causing a different reaction which consists of ingestion of organisms by macrophages without granuloma formation. The histologic features of acute pulmonary histoplasmosis are not well described as this form of the disease is rarely biopsied. We report the biopsy findings in 4 cases of acute pulmonary histoplasmosis, which seem to be unique to this form of Histoplasma infection. There were 3 men and 1 woman who ranged in age from 40 to 68 years. All presented acutely with fever and other flu-like symptoms. Radiographically, a solitary nodular infiltrate was present in 3 and bilateral reticulonodular infiltrates in one. Histologically, all 4 biopsies showed a nodular parenchymal inflammatory infiltrate composed of lymphocytes and histiocytes filling alveolar spaces and expanding the adjacent interstitium. Areas of parenchymal necrosis were additionally present in 3 cases. Vasculitis composed of lymphocytes and histiocytes was present in all, and was striking in 3, resulting in a resemblance to grade 1 lymphomatoid granulomatosis (LYG). Tip-offs to the correct diagnosis were small necrotizing granulomas scattered within the lymphohistiocytic infiltrate (3 cases), scattered histiocyte aggregates, and a few multinucleated giant cells. The diagnosis was confirmed in all by the presence of Histoplasma yeasts in Grocott methenamine silver-stained slides. Acute pulmonary histoplasmosis may cause a lymphohistiocytic infiltrate with necrosis and vasculitis that is suggestive of LYG. This observation emphasizes the importance of examining special stains for organisms before diagnosing grade 1 LYG. PMID- 20351491 TI - Familial micronodular adrenocortical disease, Cushing syndrome, and mutations of the gene encoding phosphodiesterase 11A4 (PDE11A). AB - We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat. PMID- 20351494 TI - Expanding possibilities in the treatment of patient groups with previously difficult-to-treat patients. PMID- 20351495 TI - Current world literature. PMID- 20351496 TI - Parasystole: automaticity or re-entry? PMID- 20351498 TI - Diffusion-weighted magnetic resonance imaging of ovarian tumors: differentiation of benign and malignant solid components of ovarian masses. AB - OBJECTIVE: We evaluated the feasibility of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement in differentiating benign and malignant ovarian tumors. METHODS: Surgically proven 49 ovarian tumors (39 malignant/borderline malignant and 10 benign) were examined. RESULTS: The solid portion of all 39 malignant tumors showed homogeneous or heterogeneous high intensity on DWI, whereas only 3 of the 10 benign tumors (3 thecomas) showed high intensity. The mean (SD) ADC value in the 39 malignant tumors (1.03 [0.19]) was significantly lower than that in 10 benign tumors (1.38 [0.30]). A relatively low ADC (1.08-1.20) in the 3 thecomas may reflect their abundant cellular nature, and the presence of low intensity on T2-weighted images was suggestive for benign fibrous tumor. CONCLUSIONS: Low intensity on DWI with high ADC may suggest benign lesions; however, it may be occasionally difficult to differentiate benign and malignant lesions only on the basis of DWI. PMID- 20351497 TI - Improved characterization of focal liver lesions with liver-specific gadoxetic acid disodium-enhanced magnetic resonance imaging: a multicenter phase 3 clinical trial. AB - OBJECTIVES: To evaluate the safety of gadoxetic acid disodium (Gd-EOB-DTPA) magnetic resonance imaging (MRI) and its efficacy in characterizing liver lesions. METHODS: Lesion characterization and classification using combined (unenhanced and Gd-EOB-DTPA-enhanced) MRI were compared with those using unenhanced MRI and contrast-enhanced spiral computed tomography (CT) using on site clinical and off-site blinded evaluations for patients with focal liver lesions. RESULTS: Gadoxetic acid disodium was well tolerated in this study. For the clinical evaluation, more lesions were correctly characterized using combined (unenhanced and Gd-EOB-DTPA-enhanced) MRI than using unenhanced MRI and spiral CT (96% vs 84% and 85%, respectively; P < or = 0.0008). For the blinded evaluation, more lesions were correctly characterized using combined MRI compared with using unenhanced MRI (61%-76% vs 48%-65%, respectively; P < or = 0.0012 for 2/3 readers); when compared with spiral CT, a similar proportion of lesions were correctly characterized. CONCLUSIONS: Gadoxetic acid disodium-enhanced MRI is of clinical benefit relative to unenhanced MRI and spiral CT for a radiological diagnosis of liver lesions. PMID- 20351499 TI - Mixed epithelial and stromal tumor of the kidney: an analysis of multidetector computed tomography manifestations and clinicopathologic findings. AB - OBJECTIVES: To explore the features of mixed epithelial and stromal tumor of kidney (MESTK) on the images of multidetector computed tomography with clinical manifestations and pathological findings as a reference. METHODS: On the basis of a blind retrospective review, we analyzed the images of 6 cases of MESTK on multidetector computed tomography and compared them with pathological results postoperatively. Two reviewers were asked to classify the tumors according to the Bosniak classification. We also combined them with clinical data, pathological findings, and reviewed literatures. RESULTS: All tumors were single, unilateral, and well circumscribed with a clear delineation from renal parenchyma. Five were round or oval, whereas 1 was irregularly shaped. One tumor processed to renal pelvis, 1 protruded from the cortex, and 4 large masses processed to both the cortex and the pelvis. In 6 cases, all MESTKs consisted of an irregular mixture of solid and cystic areas. The cysts were multilocular with smooth walls and low density cystic liquid. No mural nodules were observed. Five tumors were diagnosed as Bosniak III, and 1 as Bosniak IV. Solid parts presented a mild-to-moderate enhancement and delayed enhancement without any enhancement of the cystic ones. CONCLUSIONS: Radiologists should consider the possibility of MESTK when they find that the tumor is a single solid or a cystic solid mass, especially in a female patient, and that the solid components present a mild-to-moderate enhancement during the corticomedullary phase and delayed enhancement, but the definite diagnosis depends on pathology. PMID- 20351500 TI - T2-weighted magnetic resonance imaging of the liver: evaluation of the effect in signal intensity after Gd-EOB-DTPA enhancement. AB - OBJECTIVE: To evaluate the effect of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) on T2-weighted magnetic resonance imaging of liver parenchyma. METHODS: Forty-six patients with suspected hepatic tumors (group 1) underwent breath-hold T2-weighted fast spin echo imaging before and after 4 minutes of Gd-EOB-DTPA enhancement. Visual assessment and signal intensity (SI) measurements were performed to evaluate the effects of Gd EOB-DTPA on the T2-weighted images of the liver. Thirteen healthy volunteers (Group 2) who underwent magnetic resonance imaging before and after 35 minutes of Gd-EOB-DTPA enhancement were also evaluated. RESULTS: In the qualitative analysis, visual SI of hepatic vessels after enhancement was significantly higher than that before enhancement (P < 0.001) in group 1, although there was no significant difference in the visual SI of liver parenchyma between before and after enhancement. In the quantitative analysis, SI ratio of liver parenchyma on enhanced images was significantly higher than that on unenhanced images (P < 0.001) in group 1. Conversely, the SI ratio (P < 0.001) and the visual SI (P = 0.008) in group 2 were significantly lower on the enhanced images than on the unenhanced images. CONCLUSIONS: The T2-weighted images obtained during the early phase after enhancement will appear similar to those of the unenhanced T2 weighted images, whereas later images will show a reduced signal of the liver parenchyma. PMID- 20351501 TI - Gastrointestinal dissemination of mucosa-associated lymphoid tissue lymphoma: computed tomographic findings. AB - OBJECTIVE: To describe the computed tomographic findings of mucosa-associated lymphoid tissue (MALT) lymphoma with gastrointestinal (GI) tract dissemination. METHODS: We retrospectively reviewed the computed tomographic findings for the location, morphology, contrast enhancement, and continuity of the involved bowel segment with ancillary findings in 10 patients with MALT lymphoma involving multiple GI tracts. RESULTS: MALT lymphoma involved a total of 31 bowel segments. The gastric lesions appeared as segmental (n = 4) or diffuse (n = 1) wall thickening and the small- or large-intestinal lesions as circumferential wall thickening (n = 11) or localized polypoid mass (n = 8) with homogeneous and isoattenuating or hypoattenuating enhancement. Continuity of the involved bowel segment was present in 6 patients, bowel perforation in 1, lymphadenopathy in 8, and hepatosplenomegaly in 4. CONCLUSIONS: Despite its rarity, MALT lymphoma can disseminate into the GI tract in the form of circumferential bowel wall thickening or localized polypoid mass with or without gastric involvement. PMID- 20351502 TI - Communication between spaces formed by fasciae of male external genitalia and perineum: computed tomographic cadaveric study and clinical significance. AB - OBJECTIVE: The purposes were to evaluate the communication and the extent of the spaces formed by fasciae of the male external genitalia and the perineum and to correlate the spaces with clinical observations regarding anatomic progression of diseases. MATERIALS AND METHODS: Multi-detector row computed tomography (CT) was performed through the perineum and the pelvis of 5 fresh cadavers injected with contrast material in the space between dartos and Buck fasciae of the penis. Two of the 5 cadavers, injected with the contrast material mixed with blue ink, were dissected to confirm the observations made on multi-detector row computed tomography. Computed tomographic images of 11 patients with diseases involving the potential spaces formed by the fasciae of the male genitalia and the perineum were correlated with observations made on CT of the cadavers. RESULTS: The contrast material filling the scrotal cavity extended posteriorly in the perineum, remained far below the urogenital diaphragm, and reached superiorly to the potential space along Scarpa fascia in all cadavers. At cadaveric dissection, the ink-stained spaces were confined by the fascial planes involving Colles, Buck, dartos, and Scarpa fasciae. Spread of disease in the 11 patients (6 patients with localized genital edema, 4 with Fournier gangrene, and 1 with bulbous urethral rupture) was confined in the spaces demonstrated on CT images of the cadavers. CONCLUSIONS: Free communication and disease spread occur within the confines of the superficial perineal, scrotal, penile, and abdominal wall spaces formed by Colles, Buck, dartos, and Scarpa fasciae. PMID- 20351503 TI - Computed tomographic diagnosis of appendicitis within a spigelian hernia. AB - A Spigelian hernia is a rare abdominal wall hernia diagnosed with ultrasonography or computed tomography. We report the first case of acute appendicitis within a Spigelian hernia diagnosed by computed tomography. PMID- 20351504 TI - Imaging appearance of solitary fibrous tumor of the abdominopelvic cavity. AB - The computed tomographic or magnetic resonance imaging appearance of solitary fibrous tumors of the abdominopelvic cavity has previously only been presented in the English literature as individual case reports. In this article, we present the cross-sectional imaging appearance of 5 such cases, all of which exhibited highly similar imaging features, including well-circumscribed margins, lack of invasion of adjacent structures, and avid enhancement. In view of these shared imaging features, it may be possible to suggest the diagnosis preoperatively. Given their unpredictable biologic behavior with infrequent reports of recurrent or metastatic disease, complete surgical excision and long-term follow-up for these lesions is recommended. PMID- 20351505 TI - Sclerosing angiomatoid nodular transformation of the spleen: multimodality imaging findings and pathologic correlate. AB - Sclerosing angiomatoid nodular transformation of the spleen is a recently recognized benign vascular lesion, characterized microscopically by multiple angiomatoid nodules embedded within a fibrosclerotic stroma. Although its imaging manifestations have been limited in the radiologic literature, features such as low-level increased fluorodeoxyglucose activity on a positron emission tomographic scan, near-complete blending in with normal splenic parenchyma on a delayed-phase image, and the presence of radiating scarring on a magnetic resonance image may suggest the diagnosis. We report here the computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of sclerosing angiomatoid nodular transformation, along with gross and microscopic pathological correlation. PMID- 20351506 TI - Chyluria associated with radiofrequency ablation of renal cell carcinoma. AB - Chyluria is a rare condition resulting from an abnormal connection between the lymphatic and urinary collecting system and is known to occur after partial nephrectomy. We report 2 cases of chyluria in patients after radiofrequency ablation of renal cell carcinoma diagnosed on surveillance computed tomography. PMID- 20351507 TI - Gadoxetate disodium-enhanced magnetic resonance cholangiography for the noninvasive detection of an active bile duct leak after laparoscopic cholecystectomy. AB - We report a case of an endoscopically confirmed biliary leak of the common hepatic duct after laparoscopic cholecystectomy that was prospectively diagnosed on gadoxetate disodium-enhanced magnetic resonance cholangiography. Whereas dynamic contrast-enhanced magnetic resonance images during the early vascular phases helped to rule out the causes of possible complications such as seroma, hematoma, or abdominal abscess, delayed hepatobiliary phase imaging was crucial for unequivocal diagnosis and location of the biliary leak. The diagnosis prompted therapeutic endoscopic retrograde cholangiography whereby a polytetrafluoroethylene-covered nitinol stent graft was successfully placed to repair the biliary injury. PMID- 20351508 TI - Epidermoid cyst in intrapancreatic accessory spleen: radiological findings including superparamagnetic iron oxide-enhanced magnetic resonance imaging. AB - It is crucial to differentiate between nonneoplastic and neoplastic cysts of the pancreas by images. An epidermoid cyst in intrapancreatic accessory spleen (IPAS) is a rare pancreatic cyst that should be managed nonsurgically as well as other nonneoplastic cyst. However, the imaging features of an epidermoid cyst in IPAS have not been organized. We therefore reviewed articles describing cases of epidermoid cyst in IPAS, with 6 additional cases to explore the imaging findings. PMID- 20351509 TI - Intracellular lipid in ovarian thecomas detected by dual-echo chemical shift magnetic resonance imaging: report of 2 cases. AB - Thecoma of the ovary is a stromal tumor composed of lipid-containing cells with a variable component of fibroblasts. To our knowledge, there have been no reports in the English literature describing detection of intracellular lipid in thecomas by preoperative imaging. We present 2 cases of thecomas of the ovary, in which intratumoral lipid was detected using dual-echo chemical shift magnetic resonance imaging. PMID- 20351510 TI - Image fusion as a new postprocessing method to evaluate the radiofrequency ablation zone after treatment of malignant liver tumors. AB - OBJECTIVE: We describe a manual segmentation and image fusion method to assess the relationship between liver tumors and the radiofrequency ablation zone depicted on cross-sectional imaging. CONCLUSIONS: Manual fusion of segmented images of hepatic tumors from a preprocedural scan with the ablation zone depicted on the postinterventional imaging examination may be used to create a composite image demonstrating the ablation margin. This technique may improve evaluation of the size of the ablation margin around the circumference of the tumor, thereby predicting which patients are more likely to incur local tumor recurrence. PMID- 20351511 TI - Impact of hindsight bias on interpretation of nonenhanced computed tomographic head scans for acute stroke. AB - OBJECTIVE: To determine whether knowledge of the presence or the absence of acute stroke from review of follow-up studies, including diffusion-weighted magnetic resonance imaging (DW-MRI) head scans, biases the retrospective review of a radiologist's detection of acute stroke on nonenhanced computed tomographic (CT) scans of the head. METHODS: Forty-four consecutive patients with acute cerebral infarction as defined by positive DW-MRI and a CT scan within 48 hours before the MRI were identified. In addition, 30 control patients with negative DW-MRI results and a head CT scan within 48 hours before the MRI were chosen. Medical records were examined, and the time from onset of symptoms was recorded when this was available. The CT examinations were shown to 6 board-certified radiologists (of which 4 were certificate of added qualification neuroradiologists). The radiologists were asked to provide a probability estimate on whether an acute stroke is present or absent, the location of the stroke if present, and the presence of early ischemic signs including parenchymal hypoattenuation, sulcal effacement, and loss of gray-white matter differentiation. The radiologists had access to the patients' age, sex, and date of study but were not provided with the presenting history. After a minimum 10-day washout period and after reshuffling the cases, the radiologists were asked to reinterpret the examination results after first being shown the DW-MRI of the study in question and allowed access to reports and other follow-up studies. Receiver operating characteristic analysis was performed. RESULTS: For infarctions in the middle cerebral artery, the posterior fossa, and anterior cerebral artery territories, there was a significant increase in performance with knowledge of DW-MRI results than without prior knowledge of the DW-MRI findings. When the basal nuclei and the posterior cerebral artery were included, the difference in performance of the readers without and those with DW-MRI approached significance (t = 2.35, P = 0.0571). CONCLUSIONS: Knowledge of the presence or the absence of an acute infarct influences a radiologist's ability to detect the lesion on CT. The presence of hindsight bias may influence the testimony of expert witnesses in legal cases and have an impact on quality assurance procedures on a hospital level. PMID- 20351512 TI - Clinical significance of magnetization transfer contrast imaging for edematous changes in masticatory muscle. AB - OBJECTIVE: To evaluate inflammatory changes in masticatory muscles by magnetization transfer contrast (MTC) imaging. METHODS: Gradient-recalled echo (GRE) and MTC-GRE images of relaxed masticatory muscles in 28 healthy volunteers were obtained before and after exercise. At the same time, muscle stiffness and pain in the masseter muscles were also measured. Magnetization transfer ratios (MTRs) of the muscles were calculated from the GRE and MTC-GRE images. The MTRs of the masticatory muscles in 50 patients with temporomandibular disorder were compared with those in the volunteers. RESULTS: Immediately after the exercise, the MTRs of the masseter muscles significantly decreased (P < 0.05), whereas muscle stiffness and pain increased in the healthy volunteers. In patients with masseter muscle pain, the MTRs of the masseter muscles were significantly lower than in the healthy volunteers (P < 0.05). CONCLUSIONS: Magnetization transfer contrast imaging strongly reflects the masticatory muscle edematous changes, possibly leading to masseter muscle pain. PMID- 20351513 TI - Hybrid of opposite-contrast magnetic resonance angiography of the brain by combining time-of-flight and black blood sequences: its value in moyamoya disease. AB - OBJECTIVE: We assessed the value of a new magnetic resonance angiography (MRA) technique named hybrid of opposite-contrast (HOP) MRA in the diagnosis of moyamoya disease. METHODS: Using a dual-echo sequence, we obtained the first echo for time-of-flight (TOF) MRA followed by the second echo for black blood MRA. We then subtracted the black blood MRA data set from that of the TOF MRA followed by maximum-intensity projection. In 14 patients, we performed HOP MRA and compared the findings with those on 3-dimensional TOF MRA and MR images. The HOP MRA was also compared with a radionuclide perfusion study (7 patients). RESULTS: The HOP MRA technique improved the demonstration of distal arteries in 13 patients. The findings in HOP MRA correlated with MR images in 9 patients as well as with the perfusion study in 6 patients. CONCLUSIONS: The HOP MRA technique demonstrated the distal arterial branches in moyamoya disease well and facilitated the perfusion assessment with MR imaging. PMID- 20351514 TI - Multiple cranial nerve enhancement in mitochondrial neurogastrointestinal encephalomyopathy. AB - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease that often presents with nonspecific white matter abnormalities on magnetic resonance imaging. Ptosis and ophthalmoparesis are a part of its clinical features. We report multiple cranial nerve contrast enhancement on magnetic resonance imaging in a patient with MNGIE and postulate that demyelination may be the responsible substrate for this previously unreported finding. This finding may also explain the cranial neuropathies that patients with MNGIE have. PMID- 20351515 TI - Large subdural effusions after angiography mimicking acute subdural hematoma. AB - Contrast enhancement of the brain parenchyma and ventricular and subarachnoidal contrast extravasation are known to be rare complications after intra-arterial angiography. We here describe the first case of extensive contrast extravasation into the subdural space after percutaneous coronary intervention. PMID- 20351516 TI - Magnetic resonance imaging demonstration of a single lesion causing Wallerian degeneration in ascending and descending tracts in the spinal cord. AB - A magnetic resonance image of a 50-year-old man with a remote history of cervical spine injury showed focal myelomalacia at C5 and hyperintense areas on T2 weighted images laterally and posteriorly in the cord above and below C5. We believe these lesions to be due to Wallerian degeneration, with the cephalocaudal level of the Wallerian degeneration lesions dependant on the direction of the tracts relative to the C5 lesion. PMID- 20351517 TI - Computed tomographic angiography and digital subtraction angiography findings in popliteal artery entrapment syndrome. AB - OBJECTIVE: To evaluate computed tomographic angiography (CTA) and digital subtraction angiography (DSA) findings in popliteal artery entrapment syndrome (PAES). METHODS: Nine patients (13 limbs) who underwent surgical treatment for PAES were evaluated retrospectively. All cases showed various anomalous relationships between the popliteal artery and the neighboring muscular structures. Both CTA and DSA were performed on each affected limb. RESULTS: Computed tomographic angiography showed the detailed anatomy of the region well enough and established the diagnosis of PAES in all of the cases. Characterization and classification based on CTA imaging were consistent with surgical photography. Deviation, occlusion, aneurysm, and stenosis of popliteal artery can be demonstrated by CTA and DSA. Digital subtraction angiography was diagnostic in 6 limbs in 5 patients. CONCLUSION: Computed tomographic angiography can demonstrate both the vascular changes and the anatomic variations in the popliteal fossa and may be valuable in the diagnosis of PAES. PMID- 20351518 TI - Isotropic 3-dimensional fast spin echo imaging versus standard 2-dimensional imaging at 3.0 T of the knee: artificial cartilage and meniscal lesions in a porcine model. AB - PURPOSE: To compare different fat-saturated (FS) 3-dimensional (3D) intermediate weighted (IM-w) fast spin echo (FSE) sequences with a standard FS 2-dimensional (2D) IM-w FSE sequence using a porcine in vitro model with artificially created cartilage and meniscus lesions. METHODS: Using a ceramic scalpel, cartilage lesions with different depths and sizes were created in porcine knee specimens at the patella as well as the medial and lateral femoral and tibial cartilage. In addition, lateral and medial meniscal lesions were produced. Magnetic resonance imaging was performed at 3.0 T in sagittal plane using an 8-channel knee coil. A standard FS 2D IM-w FSE sequence and 3 newly developed isotropic 3D FSE sequences: (i) non-FS echo train length (ETL): 78, (ii) FS ETL: 44, and (iii) FS ETL: 44, were used. The images were independently analyzed by 4 radiologists concerning image quality (1 = optimal image quality, 4 = substantially limited quality) and absence or presence of lesions using a 5-level confidence score (1 = definite no presence of abnormality, 5 = definite presence of abnormality). Radiologists were also asked to measure diameter and categorize the depth of cartilage lesions using a modified Noyes classification. Average scores for image quality, confidence of diagnosis, and sensitivity, specificity, and accuracy were calculated. In addition, contrast-to-noise ratios were calculated. RESULTS: Image quality was significantly (P < 0.05) lower on the 3D FSE images than on the 2D FSE images [3D (i): 1.6 (SD, 0.43); 3D (ii): 2.35 (SD, 0.7); 3D (iii): 2.35 (SD, 0.5); 2D: 1.3 (SD, 0.35)]. No significant differences in diagnostic performance were found between 3D (i) and 2D FSE sequences. However, 16% fewer lesions were correctly detected with the 3D (ii) and (iii) sequences. Sensitivity was highest for the 2D sequence, and specificity was highest for the 3D (i) sequence. Confidence scores were higher for the 3D (i) sequence than for the 2D sequence. A significant increase (P < 0.05) in correctly measured cartilage lesions size and depth was found for the 3D (i) sequence over the standard 2D FSE sequence. CONCLUSIONS: Although the 3D FSE sequence performed better in depiction and characterization of cartilage abnormalities than the standard 2D FSE sequence, we currently do not recommend to use it as substitute. For the diagnosis of meniscal defects, however, no significant improvement was found. PMID- 20351519 TI - Magnetic resonance diagnosis of tarsal tunnel syndrome due to flexor digitorum accessorius longus and peroneocalcaneus internus muscles. AB - Anomalous muscles of the ankle are common. Although they are often asymptomatic, they can sometimes cause tarsal tunnel syndrome. We report a case of tarsal tunnel syndrome due to flexor digitorum accessorius longus and peroneocalcaneus internus muscles diagnosed on magnetic resonance imaging. Recognition of the most common accessory muscles of the ankle on magnetic resonance imaging and tarsal tunnel syndrome are also reviewed. PMID- 20351520 TI - Quantification of vasa vasorum density in multi-slice computed tomographic coronary angiograms: role of computed tomographic image voxel size. AB - OBJECTIVE: This study is motivated by the possibility of using computed tomography (CT) to detect early coronary atherosclerosis by the increased CT values within the arterial wall resulting from vasa vasorum proliferation. METHODS: Coronary arteries (n = 5) with early atherosclerotic changes were injected with Microfil and scanned (micro-CT). Noise was added to the CT projection data sets (to represent the radiation exposure of current clinical CT scanners) and then reconstructed to generate 3-dimensional images at different voxel sizes. RESULTS: Higher CT values were detected because of contrast agent in vasa vasorum if voxel size was less than (150 microm)(3). Contrast in the main lumen increased the CT values dramatically at voxels greater than (100 microm)(3), whereas CT values of the same specimen without contrast in the main lumen remained constant. CONCLUSIONS: Voxel sizes less than (200 microm)(3) are needed to quantitate arterial wall opacification due to vasa vasorum proliferation. PMID- 20351521 TI - Semiquantitative assessment of cardiovascular disease markers in multislice computed tomography of the chest: interobserver and intraobserver agreements. AB - OBJECTIVE: To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings. METHODS: Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients. RESULTS: Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement. CONCLUSIONS: Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT. PMID- 20351522 TI - Alterations of anatomic relationships on chest computed tomography as a function of arm position. AB - PURPOSE: To determine the effects of arm position on the appearance of structures in the upper chest as seen on computed tomography (CT), such as clavicular angle, course of axillary vessels, pectoralis major muscle, and bicipital groove. MATERIALS AND METHODS: The study consisted of 52 chest CT examinations (32 from men and 20 from women; mean [SD] age, 64 [20] years) performed with 1 or both arms at or above the shoulder (n = 44 arms) or by the side of the body (n = 60 arms). Three chest radiologists assessed randomized CT examinations for specific anatomical structures including orientation of the bicipital groove of the humerus, appearance of the pectoralis major muscle, and the course of the axillary vessels. Orientation of the clavicle and the scapula were assessed by measuring their angles with the mid-sagittal plane. Data were analyzed using the Student t test. RESULTS: There was a significant difference in the mean angle of the clavicles with the mid-sagittal plane in arms at or above the shoulder level (41.3 +/- 11.7 degrees) compared with arms-by-side position (54.8 +/- 14.7 degrees; P < 0.0001), but no significant difference was found in scapular angles (P = 0.4). All 3 radiologists found anteriorly directed bicipital groove, flat pectoralis major, and straight course of the axillary vessels from the chest to the axilla when arms were by the side. With arms at or above the level of the shoulder, however, the bicipital groove was directed posteromedially, the pectoralis major was buckled, and the axillary vessels had an angulated course. CONCLUSION: The bicipital groove, the pectoralis muscles, the axillary vessels, or the angle of the clavicle with the mid-sagittal plane on transverse CT images can help predict the position of the arms in patients undergoing chest CT. PMID- 20351523 TI - Computed tomographic fluoroscopy-guided needle aspiration biopsy as a second biopsy technique after indeterminate transbronchial biopsy results for pulmonary lesions: comparison with second transbronchial biopsy. AB - OBJECTIVE: The purpose of this study was to compare the diagnostic performance of computed tomographic (CT) fluoroscopy-guided percutaneous transthoracic needle aspiration biopsy (NAB) and transbronchial lung biopsy (TBLB) after indeterminate bronchoscopy in patients with suspected malignant pulmonary lesions. METHODS: We included 77 patients who underwent CTF-NAB (n = 53) or TBLB (n = 24) as a second biopsy for pulmonary lesions because of inconclusive pathologic results on initial TBLB. Sensitivity, specificity, and diagnostic accuracy were calculated and compared between the 2 groups using the Fisher exact test. Sensitivity and diagnostic accuracy were also compared according to lesion depth (central vs peripheral), lesion location (upper vs lower), and lesion size (<2 vs 2-3 vs >3 cm). RESULTS: There were 50 (65%) malignant and 27 (35%) benign lesions. The overall sensitivity, specificity, and accuracy for diagnosing pulmonary lesions were 84%, 100%, and 91% for NAB and 50%, 100%, and 63% for TBLB. The sensitivity and accuracy for diagnosing pulmonary lesions were significantly different between the 2 groups (P = 0.019, and P = 0.008). The sensitivity and accuracy of TBLB for diagnosing lesions was significantly different according to the lesion size (P = 0.025, and P = 0.048). CONCLUSION: A second biopsy using CT fluoroscopy guided NAB is a useful diagnostic modality for exact diagnosis of pulmonary lesions in cases of inconclusive pathologic results on initial TBLB. PMID- 20351524 TI - Prevalence of incidental pulmonary findings and early follow-up results in patients undergoing dual-source 64-slice computed tomography coronary angiography. AB - BACKGROUND: In this study, we aimed to evaluate the incidence of pulmonary abnormalities and document early follow-up results in subjects undergoing multislice computed tomography coronary angiography for the assessment of coronary artery disease. METHODS: In this retrospective analysis, 1206 patients including 701 men (58.1%) with a mean age of 58.75 (SD, 11.4) years were involved in the study who underwent coronary multislice computed tomography imaging with a 64-slice dual-source scanner. Pulmonary abnormalities were reported as nodules, pulmonary mass, emphysema, bullae, atelectasia, bronchiectasia, pleural effusion, pulmonary fibrosis, and other findings. RESULTS: In total, 186 pulmonary abnormalities were detected in 171 patients (14.1%). Of those, 90 (48.4%) were pulmonary nodules, and 30 (16.1%) were emphysema. Also, we report 3 cases of lung cancer, and 1 case of breast cancer. Early follow-up results revealed stable pulmonary findings. CONCLUSIONS: Multislice computed tomography can give important clues including diseases regarding the pulmonary system. It is essential for the reporting practitioner to review the entire scan for pulmonary pathological findings. PMID- 20351525 TI - Simulated low-dose computed tomography in oncological patients: a feasibility study. AB - OBJECTIVE: Image quality of chest and abdominal computed tomographic (CT) scans was evaluated at different doses to assess the lowest value of x-ray dose at which the image quality was not being affected. MATERIALS AND METHODS: Using multislice CT (MSCT), 29 patients who submitted to follow-up examinations were examined using a combined MSCT protocol of the chest and the abdomen on 4-raw MSCT (Siemens, Erlangen, Germany). For each examination, approximately 120 mL of contrast agent (Bracco-Altana, Konstanz, Germany) was applied intravenously. The raw data were transferred to an external personal computer equipped with an image reconstruction software (CardioRecon 6; Siemens, Forchheim, Germany) to simulate 5 different dose levels. To simulate them correctly, a milliampere second dependent noise was added to every image, so that the changes in a current-time product could be imitated. The images were compared in consensus by 2 radiologists who were not informed about the technical scanning parameters, that is, dose parameters, and were graded in 4 different subcategories on a 1-to-5 point scale. For statistical analysis, the Friedman test was used. Additional evaluations for lesions smaller than 1.0 cm were performed and analyzed separately. RESULTS: For image noise, there was a significant change between 40 and 60 mA s. For lesion detection, there was no significant change. The contour of the small objects did not differ between 90, 60, and 40 mA s. However, a dose reduction to 30 mA s had a significant effect. The contrast did not differ between 90, 60, 40, and even down to 30 mA s. Only a maximal dose reduction to 20 mA s had a significant effect on the contrast. The level of noise was most sensitive to the current. Whereas a dose reduction to 60 mA s did not yet have a significant effect, there was a significant increase of noise at 40 mA s. CONCLUSIONS: The MSCT can be applied with a lower dose than that usually selected in examinations at present to follow-up and stage the oncological patients adequately. PMID- 20351526 TI - Dual-energy computed tomography: is there a penalty in image quality and radiation dose compared with single-energy computed tomography? AB - OBJECTIVE: To assess dose and image quality of dual-energy (DE) mixed images in comparison to single-energy (SE) images. METHODS: A phantom containing iodine contrast inserts was scanned using SE and DE protocols. Dual-energy mixed images were reconstructed with varying composition ratios (ratio describing the contribution of 80 and 140 data in the mixed images). Image noise, iodine contrast, and contrast-to-noise ratios (CNRs) were assessed inside and outside the central field of view (FoV). RESULTS: With the default composition ratio (0.3), noise and contrast were comparable between both protocols in the central FoV. Peripherally, DE image noise exceeded noise in SE images; CNR in the periphery was lower in the DE images. The highest CNR was found for a composition ratio of 0.5 to 0.9, exceeding the CNR of SE images. CONCLUSIONS: Dual-energy mixed images offer an image quality comparable to SE images within the central FoV at comparable dose levels. In the peripheral FoV, image quality is decreased. By optimizing the composition ratio in the DE mixed images, higher CNRs than in the SE images can be achieved, leading to a dose reduction potential. PMID- 20351527 TI - Re: Phospho-soda-induced symptomatic hypocalcemia in a patient with cystic fibrosis and vitamin D malabsorption. PMID- 20351529 TI - Circulating viruses associated with severe complicated enterovirus infection in Taiwan: a multi-year analysis. AB - BACKGROUND: Few studies have investigated the viral isolation characteristics for severe complicated enterovirus infection (SCEI). This study evaluated the seasonality and contribution of circulated viruses to the chronologic trend and weekly reported SCEI epidemic. METHODS: Enterovirus infection surveillance and virology laboratory data in 2000 to 2008 obtained from the Centers for Disease Control in Taiwan were analyzed. We measured the monthly and weekly virology isolation rates by viral types. The virus-specific and the season-specific relative risks for SCEI and 95% confidence intervals (CI) associated with the isolated circulating viruses and weather status was evaluated. RESULTS: Among 1539 virology confirmed SCEI cases, the mean annual incidence rates ranged from 0.72/100,000 to 32.5/100,000 in children aged 5 years and less; rates were higher in warm months with cases peaking in June (12.6%). The untypeable nonpolio enterovirus was the most frequently isolated type among the monitored specimens (6.07%), followed by coxsackievirus A (3.99%), EV71 (1.77%), coxsackievirus B (1.56%), and echovirus (1.23%). However, these SCEI cases had very strong associations with the isolation of EV71 and coxsackievirus A and B. The corresponding relative risks were 1.14 (95% CI, 1.11-1.17), 1.03 (95% CI, 1.01 1.04), and 1.09 (95% CI, 1.07-1.12), respectively, for 1% increase in weekly isolation rate. CONCLUSIONS: Isolation rates for EV71 and coxsackieviruses A and B can predict the development of SCEI cases, particularly in warm months. PMID- 20351530 TI - Antiretroviral therapy in HIV-infected infants and children. PMID- 20351531 TI - First isolation of a oseltamivir-resistant influenza A (H1N1) strain in Argentina. PMID- 20351532 TI - The "starry-sky" appearance of tubercular meningitis. PMID- 20351533 TI - Development of oseltamivir resistance during oseltamivir therapy in a child with severe 2009 H1N1 influenza. PMID- 20351534 TI - Surfactant replacement therapy in influenza A H1N1. PMID- 20351535 TI - Serologic diagnosis of human bocavirus infection in children. PMID- 20351536 TI - From the editor. Quality management for health care. PMID- 20351537 TI - Utilizing DMAIC six sigma and evidence-based medicine to streamline diagnosis in chest pain. AB - AIM: The purpose of this study was to quantify the difference between the current process flow model for a typical patient workup for chest pain and development of a new process flow model that incorporates DMAIC (define, measure, analyze, improve, control) Six Sigma and evidence-based medicine in a best practices model for diagnosis and treatment. METHODS: The first stage, DMAIC Six Sigma, is used to highlight areas of variability and unnecessary tests in the current process flow for a patient presenting to the emergency department or physician's clinic with chest pain (also known as angina). The next stage, patient process flow, utilizes DMAIC results in the development of a simulated model that represents real-world variability in the diagnosis and treatment of a patient presenting with angina. The third and final stage is used to analyze the evidence-based output and quantify the factors that drive physician diagnosis accuracy and treatment, as well as review the potential for a broad national evidence-based database. RESULTS: Because of the collective expertise captured within the computer-oriented evidence-based model, the study has introduced an innovative approach to health care delivery by bringing expert-level care to any physician triaging a patient for chest pain anywhere in the world. Similar models can be created for other ailments as well, such as headache, gastrointestinal upset, and back pain. CONCLUSIONS: This updated way of looking at diagnosing patients stemming from an evidence-based best practice decision support model may improve workflow processes and cost savings across the health care continuum. PMID- 20351538 TI - Decreasing extremes in patient waiting time. AB - INTRODUCTION: We present a conceptual framework for approaching reducing excessive patient wait time in an outpatient setting. We hypothesized that statistical process control techniques can be used to identify extremes in waiting time; root cause analysis can be used to identify specific delay causes; and minimizing the contribution of the root causes will lead to an improvement in system performance. SUBJECT AND METHOD: We conducted a prospective study of waiting times in a private outpatient clinic providing high-risk obstetrical care. The baseline period consisted of 55 clinic sessions, and the intervention period consisted of 101 clinic sessions. RESULTS: Mean waiting time was prolonged during 9 (16.4%) baseline clinic sessions. The root cause analysis determined that appointment schedule, physician tardiness, and patient complexity contributed to clinic delays. After making changes to minimize root causes, there was a significant reduction in prolonged waiting times (16.4% vs 4.9%, Yates chi(2) = 4.37, P = .037); a significant decrease in mean waiting time (32.7 +/- 23.6 minutes vs 29.3 +/- 21.2 minutes, t = 3.42, P < .001); and a significant improvement in the waiting time distribution (Kruskal-Wallis test of homogeneity, P = .003). CONCLUSIONS: Our methodology was successful in identifying and reducing factors associated with prolonged wait times. However, although system operation was improved, as defined by a decrease in the occurrence of excessive clinic delays, effecting a large and sustained decrease in patient waiting times was challenging. PMID- 20351539 TI - Measurement of substance abuse treatment outcomes over time. AB - There are many different ways of calculating the impact of treatment on drug use; percentage of positive drug tests, probability of drug use, percentage of patients abstaining from any use, total number of days of use, daily probability of use and average days till next use, are some examples reported in the literature. We prefer average days till next use because (1) it allows intermittent drug use and relapse; (2) it fits the client's count of drug-free days, and (3) it simultaneously accounts for both tests results and time between tests. We show by way of an example, how conclusions arrived at using average days till next use are likely to be different from other measures in analysis of recent data from impact of online treatment on drug use. PMID- 20351540 TI - Perioperative nurses' ability to think critically. AB - AIMS: The purpose of this quantitative descriptive correlational study was to assess for presence and degree of critical thinking skills among perioperative (OR) nurses. BACKGROUND: Critical thinking has become a multidisciplinary "buzz phrase"; however, critical thinking, reflective thinking, or mental discipline was discussed among educators, as early as 1912. As nurses' roles change in response to the dynamics of managed care and an increase in use of biotechnology in health care, more is expected of nurses in terms of both psychomotor and cognitive skills. Thus, critical thinking may be central to nurses' ability to meet the care expectations of patients and the skill expectations of managers, peers, and themselves. SETTING: Data collected from 1 university-affiliated medical center, 1 non-university-affiliated medical center, and 3 ambulatory surgicenters. Data were collected over a 12-month period from 2008 to 2009. SAMPLE: Convenience sample of 92 OR nurses. The sample comprised nurses with various educational levels for entry into practice: diploma, associate, and bachelor of science in nursing degrees. Subjects' clinical experience ranged from 1 month to 40 years. INSTRUMENTS: Administered California Critical Thinking Disposition Inventory; Assessment of Critical Thinking Skills of Perioperative Nurses, an investigator-developed tool; and a demographic survey. ANALYSES: Descriptive statistics, multiple regression, and step-wise regression were performed; power of 80% with a medium effect size was calculated. RESULTS: Aggregate (N = 92) for the dependent variable (level of critical thinking)and predictor variables (dispositions) were not significant. The group (medical center 1) indicated that as the level of critical thinking increased, the level of truth increased. Also, as the level of critical thinking increased, the level of open-mindedness decreased. In groups 2, 4, and 5 (surgicenters) coefficient indicated that none of the predictors were significant. A stepwise regression was calculated for group 3 (medical center 2) to find the best predictor model. As the level of critical thinking decreased, open-mindedness increased. CONCLUSIONS: Critical thinking skill may be related to organizational culture, geography, and/or specialization. Specialization competencies may act as barriers to the development of critical thinking skills. This could be highly detrimental to the anticipation of significant negative patient outcomes within an OR setting. PMID- 20351541 TI - Effects of nurse staffing on hospital-acquired conditions and length of stay in community hospitals. AB - BACKGROUND: Error-free care is the goal of health care professionals, consumers, and public policy makers. Because nurses can be the last barrier between a patient and an error, there is a need to examine this pressing nursing issue nurse staffing. PURPOSE: This research examined the predictive relationships between nurse staffing and patient outcomes in hospitals. METHOD: A quantitative, cross-sectional design was used to examine data on nearly 35,000 patients from 11 medical-surgical units in 4 hospitals. Data were extracted from administrative databases over a 2-year period and were analyzed using hierarchical linear modeling. DISCUSSION: Findings from the study indicated that higher registered nurse (RN) and licensed practical nurse hours per equivalent patient day and higher percentages of RNs in the skill mix predicted a lower number of adverse events and shorter lengths of stay, controlling for patient age and complications. CONCLUSION: This study, with its improved methodology, supports previous findings and should be used as evidence for changes to nurse staffing. PMID- 20351542 TI - The integration of quality management into chronic disease health services. AB - Quality management strategies can be integrated into health services and processes to evaluate, measure, and improve the health services delivered to patients. Over a 6-month period, Living Well with a Chronic Condition program, a chronic disease management health service, had its support services evaluated and significantly improved, reducing the delays that participants experienced trying to access education and exercise classes. Through the use of quality management tools, including process mapping, performance data collection and evaluation, and participant feedback, the program intake process was improved significantly. Wait times of up to 90 days, with an average of 45 days, were reduced to less than 1 week. Postimprovement measures continued to demonstrate improved service, indicating that involving the staff and participants in quality management strategies can lead to significant optimization of services to participants. PMID- 20351543 TI - The relationship between incident reporting by nurses and safety management in hospitals. AB - AIM: This study examines the relationship between nurses' perceptions of incident reporting, the frequency of incident reporting on wards, and safety management in hospitals. METHODS: A self-administered survey was conducted on 528 nurses in 8 hospitals that provide core medical care in rural areas of Japan. Each of these hospitals is equipped with more than 90 beds. The relationship among perceptions of incident reporting, the frequency of incident reporting on wards, and safety management was examined using Pearson correlation coefficients calculated using ward scores. RESULTS: Safety managers' attitudes and safety management at the ward level were found to have significant correlation with fear of reprisal caused by incident reporting, willingness to carry out incident reporting, and recognition of the importance of incident reporting. CONCLUSIONS: On wards where staff and safety managers discuss incidents and their root causes, staff are less fearful of incident reporting, understand the significance of incident reporting, and report incidents more willingly. There is a need for ward managers not only to demonstrate leadership in terms of safety management but also to discuss incidents with staff. PMID- 20351544 TI - Understanding quality perception gaps among executives, frontline employees, and patients: the outpatient services in Taiwan hospitals. AB - The purpose of this study was to identify and evaluate service quality gaps among 3 roles (ie, hospital executives, frontline employees, and outpatients). A modified Chinese SERVQUAL scale was used to pinpoint dimension-specific quality gaps. A total of 1556 subjects (including 685 outpatients, 787 frontline employees, and 84 executives) were randomly selected from 12 middle-sized hospitals across Taiwan. Significant quality gaps among the 3 roles for 5 dimensions were found. Accordingly, strategies and tactics for improving service quality of hospitals are discussed. PMID- 20351547 TI - Association between polymorphisms of ERCC1 and XPD and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer. AB - BACKGROUND AND OBJECTIVE: DNA repair capacity is correlated with sensitivity of cancer cells toward platinum-based chemotherapy. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in polymorphisms of DNA repair gene ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) were associated with the tumor response in advanced non-small-cell lung cancer (NSCLC) patients received platinum-based chemotherapy in Chinese population. METHODS: Totally 115 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 cycles. Three dimensions (3-D) polyacrylamide gel-based DNA microarray method was used to evaluate the genotypes of ERCC1 Asn118Asn (354 CT), Gln504Lys (8092 CA) and XPD Lys751Gln (35931 AC). RESULTS: The C->T change of ERCC1 Asn118Asn polymorphism and the C->A change of ERCC1 Gln504Lys polymorphism have statistically significant association with elevated or descendent platinum-based chemotherapy response respectively. CONCLUSION: The polymorphic status of ERCC1 might be the promising ancillary marker for predicting treatment response of advanced stage NSCLC patients. The DNA microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals. PMID- 20351548 TI - Antitumor effects by Wilfoside C3N treatment in ECA109 cells. AB - C21 steroidal glycoside (C21) is one of the most bioactive compounds of Cynanchum auriculatum Royle, known as Baishouwu, and possesses potent antitumor activity. Wilfoside C3N is one of the two most abundant and active C21 in it. The aim of this study was to further investigate the antitumor activity of C3N and to clarify its signaling pathway. The growth inhibition ofECA109 cells induced by C3N was assessed. Western blot analysis, reverse-transcription PCR, caspase-2 and Fas activity assay, and knockdown of caspase-2 with siRNA were used to study the apoptotic mechanisms. We showed that C3N inhibited the proliferation of ECA109 cells moderately in a dose and time-dependent manner and induced apoptosis in the ECA109 cell line through a mitochondrial pathway by triggered cytochrome c release from the mitochondria, with caspase-2 functioning upstream of caspase-9 rather than association with Fas and caspase-8. Furthermore, C3N-driven apoptotic events were associated with downregulation of Bcl-2. These results suggest that C3N-induced apoptosis of ECA109 cells in vitro was dependent on caspase-2 or mitochondria or caspase-9 and independent of the Fas-FasL or caspase-8 pathway. PMID- 20351549 TI - Cardiac biomarkers - the old and the new: a review. AB - Biomarkers are biological parameters that can be objectively measured and quantified as indicators of normal biologic processes, pathogenic processes, or responses to a therapeutic intervention. Typically thought of as disease process screening, diagnosing, or monitoring tools, biomarkers may also be used to determine disease susceptibility and eligibility for specific therapies. Cardiac biomarkers are protein components of cell structures that are released into circulation when myocardial injury occurs. They play a pivotal role in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndrome and those with acute exacerbations of heart failure. Cardiac markers are central to the new definition of acute myocardial infarction put forward by the American College of Cardiology and the European Society of Cardiology. Active investigation has brought forward an increasingly large number of novel candidate markers but few have withstood the test of time and become integrated into contemporary clinical care because of their readily apparent diagnostic, prognostic, or therapeutic utility. PMID- 20351550 TI - Guideline-recommended secondary prevention drug therapy after acute myocardial infarction: predictors and outcomes of nonadherence. AB - BACKGROUND: Guideline-recommended pharmacotherapy after myocardial infarction (MI) has been shown to reduce cardiovascular morbidity and mortality. Our objectives were to determine factors of, and to measure outcomes associated with nonadherence after MI. DESIGN: Multicentre, prospective, observational study (Acute Coronary Syndromes Registry). METHODS: We analyzed data of 11,823 consecutive hospital survivors of acute MI and evaluated their discharge medication with the five following drugs: acetyl salicylic acid, clopidogrel, beta-blocker, angiotensin-converting enzyme inhibitor/sartan and statin. Patients receiving less than four drugs (group 1, n=3439, 29.1%) were compared with those receiving 4-5 drugs (group 2, n=8384, 70.9%). The impact of clinical, demographic and treatment factors on not prescribing each of these five drugs at discharge was investigated by using multiple logistic regression models. RESULTS: Patients of group 1 were older, had more comorbidities, more frequently suffered a nonST elevation MI and less often received reperfusion therapy. In the multivariate analysis, group 1 was associated with an increased risk for death at 1-year follow-up [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.4-1.9]. After adjustment for confounding variables chronic oral anticoagulation was the strongest predictor for not receiving acetyl salicylic acid (OR: 19.6, 95% CI: 15.9-24.0) at discharge, no percutaneous coronary intervention within 48 h for not receiving statin (OR: 2.1, 95% CI: 1.9-2.4) and clopidogrel (OR: 10.4, 95% CI: 9.4-11.5), chronic obstructive lung disease for not receiving beta-blocker (OR: 4.2, 95% CI: 3.6-4.9) and chronic renal insufficiency for not receiving angiotensin-converting enzyme inhibitor/sartan (OR: 2.8, 95% CI: 2.2-3.5). CONCLUSION: In clinical practice guideline-adherent secondary prevention drug therapy is linked with an improved 1-year survival. Comorbidities and no interventional treatment were strong negative predictors for guideline-adherent discharge medication. PMID- 20351551 TI - Asymptomatic carotid lesions add to cardiovascular risk prediction. AB - AIM: To show that subclinical atherosclerosis (subclinical-ATS) of carotid arteries [intima-media thickness (IMT) or asymptomatic carotid plaque (ACP)], may provide additional information for risk stratification, in asymptomatic patients, aged greater than 45 years, with a cluster of risk factors (RFs). METHODS AND RESULTS: We studied 558 asymptomatic patients (235 males). RFs for atherosclerosis were assessed and the 10-year-risk was calculated according to the Italian risk score. Doppler ultrasound of carotid arteries identified the presence of IMT greater than 0.9 mm in 183 patients and ACP in 147 patients. One hundred and fifty-three patients developed cerebrovascular or cardiovascular (CV) events in the follow-up: 67 developed acute myocardial infarction, 39 developed angina, 25 had a stroke or transient ischemic attack, six died for CV events, and 16 underwent percutaneous or surgical revascularization. The incidence reflected the different risk profiles (4, 14, and 20%, respectively). However, in patients with baseline subclinical-ATS the incidence of events increased to 35, 46, and 63%, respectively. In the multivariate analysis the incidence of events was significantly influenced by the presence of asymptomatic carotid lesions in each risk category. CONCLUSION: In our experience, the incidence of CV events is enhanced in patients with subclinical-ATS. Increased IMT and ACP predict CV events and improve the risk stratification of asymptomatic patients aged greater than 45 years and with a cluster of RFs, in a long-term follow-up. PMID- 20351552 TI - Italian cardiovascular mortality charts of the CUORE project: are they comparable with the SCORE charts? AB - BACKGROUND: The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries. DESIGN: Random population samples enrolled in the 1980s and 1990s in Italy were included in the analysis: 7,520 men and 13,127 women aged 35-69 years without previous cardiovascular events and with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE project were considered when they appear as first cause of death. METHODS: Sex-stratified Cox proportional hazard model including age, systolic blood pressure, ratio between total and HDL cholesterol, and smoking habit as risk factors was used to assess cardiovascular mortality. RESULTS: Analysis showed that all risk factors included in the model were statistically significant. The corresponding area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.803-0.846) for men and 0.850 (0.823-0.877) for women. The CUORE project charts yielded similar results to the corresponding charts of the SCORE project: Lin's coefficient was 0.929 for men and 0.935 for women. CONCLUSION: The comparison between CUORE and SCORE mortality risk charts shows that SCORE charts reflect quite well the Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE project are quite representative of European countries at low risk for cardiovascular mortality. PMID- 20351553 TI - Aspirin and risk of renal cell cancer in Italy. AB - Aspirin and nonsteroidal anti-inflammatory drugs have been related to decreased risk of several cancers, but studies on the relation with the risk of renal cell cancer (RCC) are inconsistent. A case-control study of RCC was conducted in Italy between 1992 and 2004. Cases were 755 patients with incident, histologically confirmed RCC, and controls were 1297 patients in hospital for acute non neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were conditioned on center, sex, age, and year of interview, and adjusted for education, smoking, alcohol consumption, diabetes, and hypertension. Regular use of aspirin for at least 6 months was reported by 67 cases and 99 controls, corresponding to an OR of 0.98 (95% CI 0.69-1.38). The ORs were 0.91 (95% CI 0.55 1.50) in regular users for less than 3 years, and 1.04 (95% CI 0.67-1.63) in users for 3 years or longer; 0.47 (95% CI 0.20-1.12) when aspirin was used as analgesic and 1.10 (95% CI 0.75-1.62) when it was used for cardiovascular disease prevention. No significant heterogeneity was found for regular use of aspirin across strata of age and sex. This study, based on a large dataset, suggests that regular use of aspirin did not increase RCC risk. PMID- 20351556 TI - Marx's line of the upper lid is visible in upgaze without lid eversion. AB - OBJECTIVE: To determine whether Marx's line of the upper lid is visible in upgaze without lid eversion, thus raising the possibility that the line may not be the contact area for the upper lid wiping of the ocular surfaces. METHODS: Consecutive patients in a broad-spectrum practice were enrolled. Exclusion criteria included patients of Asian descent, active anterior segment pathology, obvious lid alterations or deformities, strabismus more than 20Delta. A 20-microL drop of 2% fluorescein was instilled into the lower eyelid conjunctival sac. The complete length of the upper lid margin, in upward fixation (approximately 45 degrees , with the eyes open), was examined for Marx's line. RESULTS: Sixty-eight males and 131 females were enrolled. The age range was 18 to 80 years; mean age = 51.7 +/- 14.3 years. Before eyelid eversion, Marx's line was visible in 99.0% of eyes and was visibly continuous for the entire eyelid margin length in 93.2% of eyes. CONCLUSIONS: Marx's line of the upper lid is visible in upgaze, without lid eversion, suggesting that is not the contact area for the upper lid wiping of the ocular surfaces in that position of gaze. Further research is required to determine the position and visibility of the line through all other lid positions during blinking. PMID- 20351557 TI - Lid-wiper epitheliopathy in contact lens users and patients with dry eye. AB - OBJECTIVE: To evaluate lid-wiper epitheliopathy (LWE) in contact lens users and in patients with symptoms characteristic of dry eye but with normal dry-eye tests and to compare the results with those of controls. METHODS: One hundred fifty five patients were enrolled in the study and were divided into three groups. The first group included 69 contact lens users, the second group included 46 patients with dry eye, and the third group included 40 controls. The contact lens users were also divided as symptomatic and asymptomatic according to the Standard Patient Evaluation of Eye Dryness questionnaire and Ocular Surface Disease Index. The patients were examined for LWE with three different dyes (fluorescein, rose bengal, and lissamine green). The results were compared using chi-square and T tests. RESULTS: More LWEs were detected in the contact lens and dry-eye groups compared with controls. In the contact lens group, 67% of the symptomatic patients and 32% of the asymptomatic patients showed LWE. The difference was statistically significant (P = 0.001). No significant correlation was found between LWE and the dry-eye tests (fluorescein breakup time and Schirmer test). CONCLUSIONS: LWE should be investigated in symptomatic contact lens users and in patients with symptoms characteristic of dry eye but with normal dry-eye tests. Lid wiper may traumatize the corneal epithelium and increase the sensitivity of the cornea. This could be the main cause of the symptoms in patients without any significant dry-eye test findings. PMID- 20351555 TI - Improved signs, symptoms, and quality of life associated with dry eye syndrome: hydroxypropyl cellulose ophthalmic insert patient registry. AB - OBJECTIVES: To evaluate the acceptability, ease of use, and efficacy of hydroxypropyl cellulose ophthalmic inserts in reducing signs and symptoms of moderate-to-severe dry eye syndrome (DES), and improving quality of life (QoL) and activities of daily living (ADL). METHODS: The multicenter, prospective, open label, 4-week registry comprised 520 patients with bilateral DES and a history of artificial tear use, or a desire to use artificial tears within the previous week. Visit 1 encompassed a clinical evaluation and symptom and QoL questionnaires, including the Ocular Surface Disease Index. Patients were trained to use inserts, which were used once daily, thereafter, as monotherapy or with existing therapy. At visit 2, clinical evaluation and questionnaires evaluated changes in signs, symptoms, ADL, and QoL. Adverse events were monitored throughout the registry. RESULTS: There were 418 (80.4%) completers. Statistically significant improvements in discomfort, burning, dryness, grittiness, stinging, and light sensitivity, as well as clinical signs of keratitis, conjunctival staining, and tear volume were seen (P<0.05). Mean Ocular Surface Disease Index total scores improved by 21.3% (P<0.05). Blurred vision, affecting 8.7% of patients, was the most commonly reported adverse event leading to discontinuation. CONCLUSIONS: Hydroxypropyl cellulose ophthalmic inserts significantly improved signs and symptoms of moderate-to-severe DES, as well as ADL and QoL. Benefits were additive to those seen with patients' existing care. PMID- 20351554 TI - Effectiveness of chronic hepatitis C treatment in drug users in routine clinical practice: results of a prospective cohort study. AB - OBJECTIVE: Injection drug users are often excluded from hepatitis C virus (HCV) treatment. This study compares sustained virological response, adherence, and quality of life in patients with or without a history of illicit drug use in routine clinical practice. METHODS: This is a post-hoc analysis of a prospective, observational study conducted in 1860 patients who received peginterferon alpha 2b/ribavirin combination therapy. Nondrug users (NDUs) were defined as patients without a history of drug addiction; former drug users (FDUs) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users (ADUs) as patients using illicit drugs or on opioid maintenance therapy. Virological response, adherence, and the health-related quality of life were assessed by the measure of HCV RNA in the serum, self-report and 36-item short form health survey Questionnaire, respectively. RESULTS: The analyzed population included 1038 (56%) NDUs, 578 (31%) FDUs, and 244 (13%) ADUs. About 85% of ADUs were on opioid maintenance therapy and 25% used illicit drugs. Although ADUs had a more chaotic lifestyle and more psychiatric disorders, sustained virological response of ADUs (58%) did not differ from that of NDUs (49%) and FDUs (51%) (P=0.133). Adherence rates were 39% in NDUs and FDUs, and 37% in ADUs (P=0.883). Health-related quality of life was improved in the three groups after the end of treatment. CONCLUSION: Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients. The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies. PMID- 20351559 TI - Trends in retention on antiretroviral therapy in national programs in low-income and middle-income countries. AB - OBJECTIVES: To document regional and global trends for patients retained on antiretroviral therapy (ART) 12-48 months after treatment initiation, in low income and middle-income countries. METHODS: Data reported by national programs to WHO/UNICEF/UNAIDS in 2008 were aggregated to produce regional and global estimates. The proportion of patients on ART at 12, 24, 36, and 48 months is derived from cohort monitoring systems in ART dispensing facilities. RESULTS: Of 149 countries, 70 (47%) reported on retention at 12 months, 54 (36%) at 24 months, 38 (26%) at 36 months, and 30 (20%) at 48 months. Regional and global trends showed that the majority of attrition from ART programs occurred within the first year and declined thereafter. Among countries in sub-Saharan Africa, retention on ART was estimated at 75.2% at 12 months, 66.8% at 24 months, and remained at a similar level up to 48 months. CONCLUSIONS: After high attrition in the first year, retention on ART tends to stabilize. In the literature, attrition in the first year was related to early mortality. Earlier presentation for diagnosis of HIV infection, timely screening, and access to ART are fundamental to reduce it. Countries need support in reporting on outcomes on ART. PMID- 20351558 TI - Effect of highly active antiretroviral therapy on homocysteine plasma concentrations in HIV-1-infected patients. AB - OBJECTIVE: To analyze the effect of antiretroviral therapy on homocysteine levels in HIV-1-infected patients. DESIGN: Observational, prospective study of patients with AIDS. METHODS: We included patients with HIV-1 infection naive for antiretroviral drugs. Before and after 6 months of treatment, we evaluated fasting and postoral methionine load plasma homocysteine, serum vitamins B6 and B12, and intraerythrocyte folate levels. RESULTS: We studied 69 patients who began therapy for a 6-month period. Fasting and postoral methionine load plasma homocysteine levels increased significantly after 6 months of antiretroviral therapy with respect to basal values (P < 0.001). Fasting hyperhomocysteinemia was present in 7.3% of patients before treatment and in 89.9% after 6 months of therapy (P = 0.0001). Postoral methionine load hyperhomocysteinemia was found in 4.5% of subjects before therapy vs. 98.5% at the end of study period (P = 0.001). These results were not associated with folate or vitamins B6 or B12 levels. CONCLUSIONS: In patients with HIV-1 infection, fasting and postoral methionine load plasma homocysteine levels increased after 6 months of antiretroviral treatment. Nutritional abnormalities were not responsible for hyperhomocysteinemia, suggesting that enzymatic disturbances in the metabolic pathways of homocysteine may occur. PMID- 20351560 TI - Ameliorative role of rosiglitazone in hyperhomocysteinemia-induced experimental cardiac hypertrophy. AB - The present study has been designed to explore the beneficial effect of rosiglitazone, a peroxisome proliferator activated receptor-gamma agonist, in hyperhomocysteinemia-induced cardiac hypertrophy in rats. The hyperhomocysteinemia was induced in rats by feeding L-methionine (1.7 g/kg per day orally) for 8 weeks. The development of cardiac hypertrophy was assessed by measuring ratio of left ventricular weight to body weight, left ventricular wall thickness, cardiomyocyte diameter, and mean arterial blood pressure. The extent of fibrosis was checked by biochemical and histological assessment of collagen deposition. Moreover, the oxidative stress in heart was measured in terms of an increase in thiobarbituric acid reactive substances, superoxide anion generation, and decrease in reduced glutathione levels. The treatment with rosiglitazone (5 and 10 mg/kg per day orally) started from the first day of administration of L methionine significantly abolished hyperhomocysteinemia-induced increase in left ventricular weight to body weight ratio, left ventricular wall thickness, cardiomyocyte diameter, collagen deposition, and oxidative stress without affecting serum homocysteine levels in rats. At high dose, rosiglitazone markedly reduced mean arterial blood pressure but at low dose, a significant reduction in mean arterial blood pressure was not observed in hyperhomocysteinemic rats. Hence, our results suggest that rosiglitazone provides benefit in hyperhomocysteinemia-induced cardiac hypertrophy and fibrosis in a dose-dependent manner and its protective action is independent of change in mean arterial blood pressure and serum homocysteine levels in rats. PMID- 20351561 TI - Effect of intermedin1-53 on angiotensin II-induced hypertrophy in neonatal rat ventricular myocytes. AB - OBJECTIVES: Intermedin (IMD) is coexpressed in the heart with its receptor, which suggests that it may have localized actions as a modulator of cardiac function. The present study was designed to observe the interaction between IMD and cardiac hypertrophy and the possible mechanism involved in the antihypertrophic effects of IMD1-53 in cultured neonatal ventricular myocytes. METHODS: Myocyte hypertrophy was induced by treating the cells with angiotensin II, and the hypertrophic response was characterized by a significant increase in cell surface area, protein synthesis, and BNP mRNA expression. RESULTS: Our results showed that angiotensin II led to an obvious decrease in the production, secretion, and mRNA expression of IMD and increase receptor activity modifying proteins 1, 3 mRNA expression. Moreover, IMD1-53 inhibited the angiotensin II-induced hypertrophic response and the effects of IMD1-53 were similar to those of equivalent-dose adrenomedullin and could been blocked by H89. Otherwise, in our study, IMD1-53 resulted in dose-dependent increases of cAMP production in cardiomyocytes. CONCLUSIONS: Thus, IMD and its receptor system are involved in cardiac hypertrophy, and like adrenomedullin, IMD1-53 exerts an antihypertrophic effect on neonatal cardiomyocytes and the effect can be mediated by the cAMP/PKA pathway. PMID- 20351562 TI - Comparison of thiopental, urethane, and pentobarbital in the study of experimental cardiology in rats in vivo. AB - BACKGROUND: Despite earlier research studying the influence of anesthetics in arrhythmia models, a lot of controversy remains. The aim was to compare the influence of three anesthetics (60 mg/kg thiopental, 1200 mg/kg urethane, 60 mg/kg pentobarbital intraperitoneally) on ventricular arrhythmias and to combine it with measured hemodynamic parameters to find the most suitable agent for such experiments. METHOD: In the model of ischemia- and reperfusion-induced arrhythmias in Sprague-Dawley rats, after left anterior descending coronary artery occlusion (7 minutes) and reperfusion (15 minutes), the following parameters have been measured or calculated: mortality index; ventricular fibrillation and tachycardia incidence and duration; systolic, diastolic, and mean arterial blood pressure; heart rate; myocardial index of oxygen consumption; and plasma creatine kinase concentration. RESULTS: Evident depressive action of urethane on heart rate, blood pressures, and myocardial index of oxygen consumption should be reason enough to exclude it from use in such studies. Pentobarbital had no effect on arrhythmias, whereas thiopental was antiarrhythmic. CONCLUSIONS: Pentobarbital is the most suitable anesthetic offering stable hemodynamic values during arrhythmia studies. These hemodynamic values, which were similar to physiological values in awake rats, the long arrhythmia duration during reperfusion and approximately 50% mortality index are crucial parameters for evaluating antiarrhythmic drugs. PMID- 20351564 TI - Antidiabetic drug voglibose is protective against ischemia-reperfusion injury through glucagon-like peptide 1 receptors and the phosphoinositide 3-kinase-Akt endothelial nitric oxide synthase pathway in rabbits. AB - Glucagon-like peptide 1 (GLP-1) reportedly exerts a protective effect against cardiac ischemia. We hypothesized that the alpha-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act through stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates cardiac dysfunction in rabbits after 30 minutes of coronary occlusion and 48 hours of reperfusion. Voglibose increased basal and postprandial plasma GLP-1 levels and reduced postprandial plasma glucose levels. The infarct size-reducing effect of voglibose was abolished by treatment with exendin(9-39), wortmannin, Nomega-nitro L-arginine methylester, or 5-hydroxydecanoate), which inhibit GLP-1 receptors, phosphoinositide 3-kinase, nitric oxide synthase, and K(ATP) channels, respectively. Western blot analysis showed that treatment with voglibose upregulated myocardial levels of phospho-Akt, phosphoendothelial nitric oxide synthase after myocardial infarction. The upregulation of phospho-Akt was inhibited by exendin(9-39) and wortmannin. These findings suggest that voglibose reduces myocardial infarct size through stimulation of GLP-1 receptors, activation of the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathways, and the opening of mitochondrial K(ATP) channels. These findings may provide new insight into therapeutic strategies for the treatment of patients with coronary artery disease. PMID- 20351565 TI - Effects of clopidogrel on vascular proliferation and apoptosis in an atherosclerotic rabbit model. AB - Inflammation, vascular proliferation. and apoptosis contribute to the process of atherosclerosis. Clopidogrel has been used to treat atherosclerosis; however, the mechanism is not entirely known. Compared with those of atorvastatin, we determined effects of clopidogrel on inflammatory factors, vascular proliferation, and apoptosis in an atherosclerosis rabbit model. New Zealand white rabbits were fed a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except those in the negative control group were balloon-injured 1 week after initiation of the diet, and groups of animals were treated with clopidogrel (4 mg/kg per day), atorvastatin (2.5 mg/kg per day), or placebo (positive control group) for 6 weeks. We found that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, clopidogrel- or atorvastatin-treated rabbits showed a significant reduction in progression of atherosclerosis, including a low expression of high sensitivity C-reactive protein and platelet-derived growth factor, a reduced intima thickness, and reduced ratio of bcl-2/bax in the vascular wall. These results suggest that clopidogrel can retard the progression of established lesions that is related to inhibiting inflammation, cell proliferation, and promotion of cell apoptosis. PMID- 20351566 TI - Cholesteryl ester transfer protein inhibition: a dysfunctional endothelium. PMID- 20351567 TI - Submucosal injection of 0.4% hydroxypropyl methylcellulose facilitates endoscopic mucosal resection of early gastrointestinal tumors. AB - BACKGROUND AND AIMS: Submucosal injection of a viscoelastic solution prolongs submucosal lift, thus, facilitating endoscopic mucosal resection. Our objective was to assess the safety and clinical effectiveness of 0.4% hydroxypropyl methylcellulose (HPMC) as a submucosal injectant for endoscopic mucosal resection. PATIENTS AND METHODS: A prospective, open-label, multicenter, phase 2 study was conducted at 2 academic institutions in Brazil. Eligible participants included patients with early gastrointestinal tumors larger than 10 mm. Outcomes evaluated included complete resection rates, volume of HPMC injected, duration of the submucosal cushion as assessed visually, histology of the resected leisons, and complication rates. RESULTS: Over a 12-month period, 36 eligible patients with superficial neoplastic lesions (stomach 14, colon 11, rectum 5, esophagus 3, duodenum 3) were prospectively enrolled in the study. The mean size of the resected specimen was 20.4 mm (10 to 60 mm). The mean volume of 0.4% HPMC injected was 10.7 mL (range 4 to 35 mL). The mean duration of the submucosal fluid cushion was 27 minutes (range 9 to 70 min). Complete resection was successfully completed in 89%. Five patients (14%) developed immediate bleeding requiring endoclip and APC application. Esophageal perforation occurred in 1 patient requiring surgical intervention. There were no local or systemic adverse events related to HPMC use over the follow-up period (mean 2.2 mo). CONCLUSION: HPMC solution (0.4%) provides an effective submucosal fluid cushion and is safe for endoscopic resection of early gastrointestinal neoplastic lesions. PMID- 20351568 TI - Advanced synchronous adenoma but not simple adenoma predicts the future development of metachronous neoplasia in patients with resected colorectal cancer. AB - BACKGROUND: Patients with resected colorectal cancer remain at a high risk for developing metachronous neoplasia in the remnant colorectum. The aim of this study was to identify baseline clinical and colonoscopic features predictive of metachronous neoplasia after curative resection of colorectal cancer. METHODS: The baseline clinical and colonoscopic data and follow-up details of 503 patients who had colonoscopic surveillance after curative colorectal resection between January 2000 and October 2005 in a single tertiary institution were analyzed. Univariate and multivariate analyses were done to identify risk factors for metachronous adenoma. RESULTS: Metachronous adenomas were diagnosed in 176 patients (35.0%) and advanced adenomas in 39 (7.8%) during the follow-up period (35.7+/-20.9 mo). Among the clinical and colonoscopic factors at baseline, advanced age (> or = 60 y) (odds ratio (OR)=3.64; 95% confidence intervals (CI), 1.55-8.52), the presence of advanced synchronous adenoma (OR=4.38; 95% CI, 1.77 10.85), and longer total follow-up period (OR=1.03; 95% CI, 1.01-1.04) were independently correlated with developing advanced metachronous adenoma. Patients who had synchronous tubular adenoma without advanced features at baseline were not found to have an increased risk for future development of advanced metachronous adenoma compared with those in the synchronous adenoma-free group (OR=1.75; 95% CI, 0.69-4.43, P=0.650). CONCLUSIONS: Our data showed that patients with advanced synchronous adenoma at baseline were identified to have an increased risk of advanced metachronous neoplasia during a longer follow-up period but those with tubular adenoma without advanced features at baseline were not. PMID- 20351569 TI - The thyroid and the gut. AB - Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease. PMID- 20351570 TI - Low-frequency repetitive transcranial magnetic stimulation inferior to electroconvulsive therapy in treating depression. AB - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a potential new antidepressant method and alternative to electroconvulsive therapy (ECT). The efficacy of right prefrontal low-frequency rTMS was shown in a previous placebo controlled, randomized study but has never been compared with ECT. The aim of this study was to compare the antidepressant efficacy and adverse effects of right prefrontal low-frequency rTMS with that of ECT. METHODS: Sixty inpatients with major depression were randomized to 15 days of 1-Hz right prefrontal rTMS or 9 unilateral ECTs. Depressive symptoms and adverse effects were recorded using the Hamilton Scale for Depression and the Udvalg for Kliniske Undersogelser side effect scale, supplied by neuropsychological assessment of cognitive functions. RESULTS: Repetitive transcranial magnetic stimulation was significantly less effective than ECT. The intention-to-treat analysis revealed a 26% (confidence interval, 3%-51%) higher rate of partial remission (P = 0.035) by the end of week 3. There was no difference found between the 2 methods on the Udvalg for Kliniske Undersogelser rating scale. However, psychological examination revealed ECT to have more adverse effects on cognitive functions, whereas the rTMS group improved particularly with respect to visual memory. CONCLUSIONS: Repetitive transcranial magnetic stimulation was significantly less effective than ECT, but ECT had more adverse effects on cognitive function. The outcome does not point to right frontal low-frequency rTMS using the present stimulus design as a first-line substitute for ECT, but rather as a treatment option for patients with depression who are intolerant to other types of treatment or not accepting ECT. PMID- 20351571 TI - Seizure in a nonpredisposed individual induced by single-pulse transcranial magnetic stimulation. AB - Seizure induction is a rare, but serious adverse effect of the otherwise very safe method of transcranial magnetic stimulation (TMS). There are only very few single case reports concerning seizure in single-pulse TMS. All of these reports describe individuals with neurological disorders or epileptogenic medication. To our knowledge, we are the first to describe a healthy subject who developed symptoms of a seizure after single-pulse TMS during motor threshold estimation. This case report provides evidence that single-pulse TMS may provoke a seizure even in the absence of neurological risk factors. Differential diagnoses of a classic neurological seizure, that is, convulsive syncope and psychogenic seizure, are discussed. Neurogenic seizure after TMS and convulsive syncope are the most probable hypotheses, although clear specification of this singular incident remains impossible. Therefore, to minimize the risk for such rare adverse effects, existing and new suggestions are combined to provide reasonable precautions to be taken before and during TMS application. PMID- 20351573 TI - Cavernous malformation of the optic nerve mimicking optic neuritis. AB - A 30-year-old woman developed acute visual loss and optic disc elevation in the left eye after breastfeeding her second son. The initial diagnosis was optic neuritis. However, MRI showed a lesion in left intraorbital and intracanalicular optic nerve and several cerebral lesions with imaging features of cerebral cavernous malformations (CCMs). Genetic testing was positive for abnormalities known to predispose to CCMs in the patient and her father, who also showed MRI evidence of CCMs. During a 44-month follow-up period in which no intervention took place, the patient's vision in the affected eye fluctuated but eventually became extinguished. Serial MRIs did not always show lesion changes that explained the visual deterioration. In familial CCM, pregnancy might be a "second hit" to genetically predisposed tissue. PMID- 20351572 TI - Pegylated interferon alpha-associated optic neuropathy. AB - A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha 2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1-40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits. PMID- 20351574 TI - A longitudinal analysis on the validity and reliability of ratings of perceived exertion for elite swimmers. AB - The purpose of this study was to examine longitudinally the reliability and validity of ratings of perceived exertion (RPE) for monitoring exercise intensity in elite swimmers, with the percentage of maximum heart rate (%HRmax) and the blood lactate concentration (La) being the criterion measures. Moreover, the purpose was to examine whether an adjustment of HRmax, as previously suggested for recreational/university swimmers, is required for subsequent calculations of %HRmax for elite swimmers. Seventeen swimmers competing at international level performed a 7 x 200 m incremental swim test at their specialty stroke 4 times during a period of 6 months. The RPE validity was examined with the use of correlation and with repeated measures analysis of variance (ANOVA) of the z transformed values. The RPE reliability was examined with a factorial ANOVA, with %HRmax and La being the dependent variables and test (4 levels) and RPE stage (7 levels) the fixed factors. The RPE was found to be a valid method for monitoring exercise intensity, with the correlation coefficients with %HRmax and La being 0.85 and 0.82, respectively. There was a strong correspondence between RPE and %HRmax scores and a weaker correspondence between RPE and La scores, suggesting that that RPE reflects accurately the HR levels of elite swimmers. The longitudinal intertest reliability was high as no significant differences were found in the values of %HRmax or La between the 4 tests. The good validity and reliability of RPE suggest that it can be used in elite swimmers' training for the purpose of monitoring exercise intensity. Contrary to previous recommendations for recreational/university swimmers, when prescribing intensity for elite swimmers, the predicted HRmax value used for subsequent calculations should not be adjusted because such an adjustment would appear to underestimate HRmax. PMID- 20351575 TI - Effects of lifting tempo on one repetition maximum and hormonal responses to a bench press protocol. AB - This study was carried out in 2 parts: part 1 was designed to measure the 1 repetition maximum (1RM) bench press with 2 different moderate-velocity tempos (2/0/2) vs. (2/0/4) in male lifters while part 2 compared the hormonal responses at the same tempos as described in part 1. In both parts 1 and 2, the 1RMs (lbs) were higher on the 2/0/2 tempo than on the 2/0/4 tempo. The change in plasma volume (PV) was greater after the 2/0/4 tempo (-5.7 +/- 1.7% vs. 0.96 +/- 1.2%, p < 0.05). All blood parameters were significantly (p < 0.05) higher post-exercise compared with baseline. With PV corrected, insulin-like growth factor 1 (IGF-1) (ng.mL-1) was higher with the 2/0/2 tempo only (pre-exercise: 277.4 +/- 21.8, post-exercise: 308.1 +/- 22.9; 2/0/4 tempo pre-exercise: 277.2 +/- 17.6, post exercise: 284.8 +/- 21.2). In conclusion, heavier loads can be lifted and more total work can be performed using a (2/0/2) tempo compared with a slower (2/0/4) tempo, but with the exception of IGF-1, the hormonal responses are similar. Individuals may get the same metabolic responses to training by using different tempos, but they will need to use less weight at a slower tempo. PMID- 20351576 TI - Chronic and acute inspiratory muscle loading augment the effect of a 6-week interval program on tolerance of high-intensity intermittent bouts of running. AB - This study examined the hypothesis that chronic (training) and acute (warm-up) loaded ventilatory activities applied to the inspiratory muscles (IM) in an integrated manner would augment the training volume of an interval running program. This in turn would result in additional improvement in the maximum performance of the Yo-Yo intermittent recovery test in comparison with interval training alone. Eighteen male nonprofessional athletes were allocated to either an inspiratory muscle loading (IML) group or control group. Both groups participated in a 6-week interval running program consisting of 3-4 workouts (1-3 sets of various repetitions of selected distance [100-2,400 m] per workout) per week. For the IML group, 4-week IM training (30 inspiratory efforts at 50% maximal static inspiratory pressure [P0] per set, 2 sets.d-1, 6 d.wk-1) was applied before the interval program. Specific IM warm-up (2 sets of 30 inspiratory efforts at 40% P0) was performed before each workout of the program. For the control group, neither IML was applied. In comparison with the control group, the interval training volume as indicated by the repeatability of running bouts at high intensity was approximately 27% greater in the IML group. Greater increase in the maximum performance of the Yo-Yo test (control: 16.9 +/- 5.5%; IML: 30.7 +/- 4.7% baseline value) was also observed after training. The enhanced exercise performance was partly attributable to the greater reductions in the sensation of breathlessness and whole-body metabolic stress during the Yo-Yo test. These findings show that the combination of chronic and acute IML into a high-intensity interval running program is a beneficial training strategy for enhancing the tolerance to high-intensity intermittent bouts of running. PMID- 20351577 TI - Velocity at lactate threshold and running economy must also be considered along with maximal oxygen uptake when testing elite soccer players during preseason. AB - Maximal oxygen uptake (VO2max) has been traditionally used to explain physiologic differences among soccer teams of different ranking. However, other endurance markers may have greater discriminatory ability. The purpose of this study was to examine whether velocity at lactate threshold and running economy can be used to better discriminate endurance characteristics of soccer teams of different levels along with VO2max during preseason testing. One hundred twenty-nine professional Greek soccer players participating in the top 3 divisions underwent an incremental treadmill test to exhaustion using expired gas analysis and simultaneous blood lactate measurements. Velocity at lactate threshold was determined using the Dmax method, and running economy was measured at 12 km.h-1. Analyses of variation were used to compare for differences between divisions. Velocity at lactate threshold was the only variable that was statistically different between any 2 divisions. In every comparison, the higher division had the higher velocity at lactate threshold. The VO2 was statistically different only between the top 2 divisions. Running economy was statistically different between divisions with similar VO2, with better running economy for the higher division in each comparison. These results indicate that velocity at lactate threshold can be used to better discriminate endurance characteristics of soccer teams of different level along with VO2max during preseason testing. Running economy may reveal differences between teams with similar VO2max. PMID- 20351578 TI - Rosai-Dorfman disease manifesting as a mediastinal mass with calcifications. AB - Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare entity predominantly affecting children and young adults, characterized in 95% of patients by painless bilateral cervical limphadenopathy. We report the case of a 30-year-old female with an anterior mediastinal mass due to lymph node enlargement, which showed calcifications on computed tomography. To our knowledge, calcification in lymphadenopathy, as is present in this case, has never been described in Rosai-Dorfman disease. PMID- 20351579 TI - Computed tomography findings of spontaneous porto-pulmonary shunts in 3 patients with portal hypertension. AB - Spontaneous portopulmonary shunts in the setting of cirrhosis have been associated with the embolization of gelfoam during the treatment of esophageal varices, resulting in strokes. Currently there is minimal data describing the prevalence of spontaneous portopulmonary shunts. Our aim is to demonstrate computed tomography (CT) imaging findings of spontaneous portopulmonary venous anastomoses in patients with underlying portal hypertension. Clinical cases with accompanying CT images are presented and described. A review of the literature is discussed. CT is a useful method for identifying shunting, both spontaneous and surgical, of the portal circulation secondary to hypertension. A less known type of anastomosis involves the pulmonary circulation, specifically the pulmonary veins and left atrium, that can also be recognized with CT. PMID- 20351580 TI - Pulmonary hyalinizing granuloma mimicking multiple lung metastases: report of fluorodeoxyglucose positron emission findings. AB - Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search. PMID- 20351581 TI - High-resolution computed tomography findings in hantavirus pulmonary syndrome. AB - The hantavirus pulmonary syndrome (HPS) is an acute, rapidly progressive disease transmitted by rodent excreta, with endothelial damage playing a central role in the pathophysiology. It usually affects rural workers. The lung itself is the target organ and reflects all the patterns of endothelial involvement of this disease. The radiologic findings of HPS are vast and range from a mild interstitial involvement to total obliteration of the airspaces with or without pleural effusion. There are no specific findings on high-resolution computed tomography in HPS; nevertheless, findings of thickening of interlobular septa, ground-glass opacities, and occasionally small ill-defined nodular opacities have been described. The authors report a fulminant case of HPS and discuss its varied high-resolution computed tomography findings. To our knowledge, the "crazy paving" pattern has not been seen previously in such cases. PMID- 20351582 TI - Metal fume-induced diffuse alveolar damage. AB - Metal fume fever is a well-defined clinical entity characterized by a self limited influenza-like illness. Severe and protracted illness related to metal fume exposure is rare. We describe 2 related cases of serious metal fume fever in a 29- and a 51-year-old male precipitated by the use of an acetylene torch to dismantle galvanized steel in a poorly ventilated area. Each case was unusual in both severity and duration of symptoms for metal fume exposure. High-resolution computed tomography scans revealed diffuse alveolar damage in both patients. The 29-year-old male was started on steroids 1-day after exposure and experienced a significantly attenuated course of symptoms compared with the 58-year-old male, who received treatment 3 days after exposure. PMID- 20351583 TI - Primary tracheal non-Hodgkin lymphoma: case report with an emphasis on computed tomography findings. AB - A 24-year-old male presented with productive cough associated with fever, dyspnea, and hoarseness. A chest radiograph showed nonhomogeneous air-space consolidations, mainly in the middle and inferior zones of both lungs, with cavitations and peribronchial thickening. The computed tomography scan demonstrated irregular, lobulated narrowing of the trachea, and parenchymal consolidations containing air bronchogram, peribronchial thickening, and cavitations. Afterward, the patient was referred for a bronchoscopy with a biopsy of the tracheal mucosa. The samples were submitted to immunohistochemical analysis and revealed a diagnosis of diffuse large B-cell non-Hodgkin lymphoma of the trachea. A culture of bronchoalveolar lavage fluid revealed Pseudomonas aeruginosa. Antibiotic treatment was proposed as a first treatment. The patient did not receive intensive chemotherapy because of his comorbid conditions and died 2 months later. PMID- 20351584 TI - CMS changes in reimbursement for HAIs: setting a research agenda. AB - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) promulgated regulations commencing October 1, 2008, which deny payment for selected conditions occurring during the hospital stay and are not present on admission. Three of the 10 hospital-acquired conditions covered by the new CMS policy involve healthcare-associated infections, which are a common, expensive, and often preventable cause of inpatient morbidity and mortality. OBJECTIVE: To outline a research agenda on the impact of CMS's payment policy on the healthcare system and the prevention of healthcare-associated infections. METHODS: An invitational day-long conference was convened in April 2009. Including the planning committee and speakers there were 41 conference participants who were national experts and senior researchers. RESULTS: Building upon a behavioral model and organizational theory and management research a conceptual framework was applied to organize the wide range of issues that arose. A broad array of research topics was identified. Thirty-two research agenda items were organized in the areas of incentives, environmental factors, organizational factors, clinical outcomes, staff outcomes, and financial outcomes. Methodological challenges are also discussed. CONCLUSIONS: This policy is a first significant step to move output-based inpatient funding to outcome-based funding, and this agenda is applicable to all hospital-acquired conditions. Studies beginning soon will have the best hope of capturing data for the years preceding the policy change, a key element in non-experimental research. The CMS payment policy offers an excellent opportunity to understand and influence the use of financial incentives for improving patient safety. PMID- 20351585 TI - How well do hospital mortality rates reported in the New York State CABG report card predict subsequent hospital performance? AB - BACKGROUND: The use of mortality report cards as the basis for hospital choice assumes that a hospital's current performance is predicted by its past performance. OBJECTIVE: To assess the accuracy of hospital risk-adjusted mortality rates reported in the New York State (NYS) coronary artery bypass graft (CABG) report card for predicting subsequent hospital mortality. METHODS: We performed a retrospective study based on hospital mortality measures for CABG surgery (n = 37 hospitals) in NYS, which are publicly reported by the NYS Department of Health. Feasible generalized least squares was used to examine the association between a hospital's past quality ranking (high-quality, intermediate quality, low-quality) and its subsequent performance, as measured using the ratio of the observed-to-expected mortality rate (O-to-E ratio). RESULTS: Hospitals identified as low-mortality hospitals using 2-year-old data had subsequent O-to-E ratios that were 16.8% lower (95% confidence interval, 8.9-24.8; P < 0.001) than average-mortality hospitals, whereas hospitals identified as high-mortality hospitals had subsequent O-to-E ratios that were 31.8% higher (95% confidence interval, 3.69-59.9; P < 0.05) compared with average-mortality hospitals. Hospitals identified as high-mortality hospitals using 3-year-old data were indistinguishable from average-mortality hospitals. CONCLUSION: Hospital ranking based on 2-year-old data is a strong predictor of future performance. Report cards based on 3-year-old data may not be useful for identifying low-performance hospitals. We recommend that the CABG report cards in NYS should be based on 2 year-old data, as opposed to the current practice of basing them on either 2- or 3-year-old data. PMID- 20351586 TI - Medicaid prescription cost containment and schizophrenia: a retrospective examination. AB - OBJECTIVES: In 2002, the Mississippi Division of Medicaid enacted several policies to curb prescription spending including increasing prescription copayments from $1 to $3 per brand, a cap of 7 prescriptions per month, a 34-day supply limitation, and a 5% reduction in dispensing fees. The objectives of this study were to examine the influence of these policies on (1) compliance to antipsychotic medications and (2) mental health care utilization and payments among patients with schizophrenia. METHODS: This study used a 12-month pretest and 12-month posttest longitudinal design to compare the effect of these policies among patients with schizophrenia in Minnesota and Indiana, who had less restrictive cost-containment using administrative claims data. Generalized estimating equations were used to run difference in difference models to compare medication compliance (proportion of days covered) and health care utilization in Mississippi to the control states. RESULTS: After policy adoption, patients in Mississippi were 4.87% less compliant with antipsychotic treatments and experienced 20.5% more 90 day antipsychotic treatment gaps than patients in the control states. Although these policies did not affect inpatient or emergency department care among patients with schizophrenia, there was a 3.7% reduction in outpatient mental health visits and a 4.2% reduction in mental health care payments. CONCLUSIONS: Despite the potential for savings, policy makers should consider carefully the potential adverse consequences that may arise from implementing aggressive cost-containment policies among patient with severe mental illness. PMID- 20351588 TI - Cardiorespiratory fitness, adiposity, and all-cause mortality in women. AB - PURPOSE: To determine the prospective associations among cardiorespiratory fitness (CRF), different measures of adiposity, and all-cause mortality in women. METHODS: A total of 11,335 women completed a comprehensive baseline examination between 1970 and 2005. Clinical measures included body mass index (BMI), waist circumference (WC), waist-to-height ratio (W/HT), waist-to-hip ratio (W/Hip), percent body fat (%BF), and CRF quantified as duration of a maximal exercise test. Participants were classified by CRF as low (lowest 20%), moderate (middle 40%), and high (highest 40%) as well as by standard clinical cut points for adiposity measures. Hazard ratios (HR) were computed using Cox regression analysis. RESULTS: During a mean follow-up of 12.3 +/- 8.2 yr, 292 deaths occurred. HR for all-cause mortality were 1.0, 0.60, and 0.54 for low, moderate, and high fit groups, respectively (P for trend G0.01). Adjusted death rates of overweight/obese women within each adiposity exposure were somewhat higher compared with normal-weight women and approached statistical significance for BMI, %BF, and W/HT (P = 0.08, P = 0.08, and P = 0.07, respectively). When grouped for joint analyses into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), HR were significantly higher in unfit women within each stratum of BMI compared with fit-normal BMI women. Fit women with high %BF (HR = 1.0), high WC (HR = 0.9), and high W/HT (HR = 1.2) had no greater risk of death compared with fit-normal-weight women (referent). CONCLUSIONS: Low CRF in women was a significant independent predictor of all-cause mortality. Higher CRF was associated with lower mortality within each category of each adiposity exposure. Using adiposity measures as predictors of all-cause mortality in women may be misleading unless CRF is also considered. PMID- 20351587 TI - Strength exercise improves muscle mass and hepatic insulin sensitivity in obese youth. AB - INTRODUCTION: Data on the metabolic effects of resistance exercise (strength training) in adolescents are limited. PURPOSE: The objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss reduces body fat accumulation, increases lean body mass, and improves insulin sensitivity and glucose metabolism in sedentary obese Hispanic adolescents. METHODS: Twelve obese adolescents (age = 15.5 +/- 0.5 yr, body mass index = 35.3 +/- 0.8 kg.m; 40.8% +/- 1.5% body fat) completed a 12-wk resistance exercise program (two times 1 h.wk, exercising all major muscle groups). At baseline and on completion of the program, body composition was measured by dual-energy x-ray absorptiometry, abdominal fat distribution was measured by magnetic resonance imaging, hepatic and intramyocellular fat was measured by magnetic resonance spectroscopy, peripheral insulin sensitivity was measured by the stable-label intravenous glucose tolerance test, and hepatic insulin sensitivity was measured by the hepatic insulin sensitivity index = 1000/(GPR * fasting insulin). Glucose production rate (GPR), gluconeogenesis, and glycogenolysis were quantified using stable isotope gas chromatography/mass spectrometry techniques. RESULTS: All participants were normoglycemic. The exercise program resulted in significant strength gain in both upper and lower body muscle groups. Body weight increased from 97.0 +/- 3.8 to 99.6 +/- 4.2 kg (P < 0.01). The major part (~80%) was accounted for by increased lean body mass (55.7 +/- 2.8 to 57.9 +/- 3.0 kg, P <= 0.01). Total, visceral, hepatic, and intramyocellular fat contents remained unchanged. Hepatic insulin sensitivity increased by 24% +/- 9% (P < 0.05), whereas peripheral insulin sensitivity did not change significantly. GPR decreased by 8% +/- 1% (P < 0.01) because of a 12% +/- 5% decrease in glycogenolysis (P < 0.05). CONCLUSIONS: We conclude that a controlled resistance exercise program without weight loss increases strength and lean body mass, improves hepatic insulin sensitivity, and decreases GPR without affecting total fat mass or visceral, hepatic, and intramyocellular fat contents. PMID- 20351589 TI - Efficacy of exercise in reducing depressive symptoms across 5-HTTLPR genotypes. AB - INTRODUCTION: Exercise is effective in the alleviation of depressive symptoms and may have physiological effects similar to those of selective serotonin reuptake inhibitors (SSRI). Recent research has identified the difference in treatment effects across genetic polymorphisms of the serotonin transporter polymorphic region (5-HTTLPR), in which the l allele has been associated with a better response to SSRI compared with the s allele. The purpose of the current research was to examine the antidepressant effects of exercise across 5-HTTLPR genotypes. METHODS: Participants, ages 18-23 yr, were randomly assigned to a 5-wk exercise intervention or a no-treatment control group. Participants completed the Beck Depression Inventory before and after the intervention and provided a saliva sample for DNA analysis. RESULTS: Exercise resulted in a significant reduction in depressive symptoms compared with the control group. In addition, individuals with at least one l allele demonstrated greater reductions in depressive symptoms compared with ss individuals. CONCLUSIONS: The effects of exercise on depressive symptoms appear to be moderated by 5-HTTLPR genotype, suggesting that the mechanisms responsible for the alleviation of depressive symptoms are similar for exercise and SSRI treatment. Furthermore, these findings suggest that 5-HTTLPR genotype should be a factor in determining the proper line of treatment for depression. PMID- 20351590 TI - Inclusion criteria when investigating insufficiencies in chronic ankle instability. AB - INTRODUCTION: The development of chronic ankle instability (CAI) is the primary residual deficit after ankle joint sprain. It has been proposed that CAI is characterized by two entities, namely, mechanical instability and functional instability. Each of these entities in turn is composed of various insufficiencies. Research of functional insufficiencies to date has shown large variances in results. One particular reason for this could be discrepancies in inclusion criteria and definitions between CAI, mechanical instability, and functional instability used in the literature. Thus, we endeavored to undertake a systematic investigation of those studies published in the area of CAI to identify if there is a large discrepancy in inclusion criteria across studies. METHODS: A systematic search of the following databases was undertaken to identify relevant studies: Cochrane Central Register of Controlled Trials, PubMed, CINAHL, SportDiscus, PEDro, and AMED. RESULTS: The results of this study indicate that there is a lack of consensus across studies regarding what actually constitutes ankle instability. Furthermore, it is evident that the majority of studies use very different inclusion criteria, which leads to a nonhomogenous population and to difficulties when comparing results across studies. CONCLUSIONS: Future studies should endeavor to be specific with regard to the exact inclusion criteria being used. Particular emphasis should be given to issues such as the number of previous ankle sprains reported by each subject and how often and during which activities episodes of "giving way" occur as well as the presence of concomitant symptoms such as pain and weakness. We recommend that authors use one of the validated tools for discriminating the severity of CAI. Furthermore, we have provided a list of operational definitions and key criteria to be specified when reporting on studies with CAI subjects. PMID- 20351591 TI - Effect of ankle taping on knee and ankle joint biomechanics in sporting tasks. AB - INTRODUCTION: Prophylactic taping is commonly used to prevent ankle injuries during sports. However, unnatural constraint of the ankle joint may increase the risk of injury to proximal joints such as the knee. The association between ankle taping and knee joint loading during open sporting tasks has not been quantified. This research aimed to measure changes in knee and ankle kinetics and kinematics during dynamic athletic activities undertaken with and without ankle taping. METHODS: A kinematic and inverse dynamics model was used to determine ankle and knee joint motion and loading in 22 healthy male participants undertaking running and sidestepping tasks. Both tasks were randomized to planned and unplanned conditions and undertaken with and without the use of ankle tape. RESULTS: At the knee, peak internal rotation moments (P < 0.001) and peak varus moments (P < 0.05) were significantly reduced during all running and sidestepping trials (planned and unplanned) when undertaken with ankle tape. Internal rotation impulse (P < 0.001) was reduced for sidestepping tasks. Varus impulse during unplanned sidestepping maneuvers (P = 0.04) was reduced with the use of ankle tape. However, there was a trend toward increased valgus moments and impulse for planned sidestepping trials undertaken with ankle tape(P = 0.056). Taping reduced the range of motion at the ankle in all three planes (P < 0.05). Peak inversion (P < 0.001) was reduced for running trials only. Average eversion and peak dorsiflexion moments were significantly reduced in sidestepping tasks by use of taping. CONCLUSIONS: By limiting motion at the ankle, taping increased mechanical stability at this joint. Ankle taping also provided protective benefits to the knee via reduced internal rotation moments and varus impulses during both planned and unplanned maneuvers. Medial collateral and anterior cruciate ligament injuries may, however, occur through increased valgus impulse during sidestepping undertaken with ankle tape. PMID- 20351592 TI - Walking and running economy: inverse association with peak oxygen uptake. AB - PURPOSE: The purpose of this study was to test the hypothesis that VO2peak is positively correlated with the regression coefficients of the curve-linear relationship between VO2 and speed during a protocol consisting of submaximal walking and running. METHODS: Nineteen healthy men (mean +/- SD: age = 26.4 +/- 6.4 yr, height = 179.9 +/- 7.2 cm, weight = 77.7 +/- 8.7 kg, % fat = 16.3 +/- 7.3) and 21 healthy women (age = 25.6 +/- 4.9 yr, height = 167.2 +/- 5.4 cm, weight = 61.6 +/- 7.7 kg, % fat = 24.0 +/- 6.8) underwent an incremental treadmill test to determine VO2peak and on two separate days performed an exercise protocol consisting of treadmill walking on a level grade at 2.0 mph (54 m.min-1), 3.0 mph (80 m.min-1), and 4.0 mph (107 m.min-1) and running at 6.0 mph (161 m.min-1). Subjects exercised for 5 min at each velocity, with 3 min of rest in between each exercise bout. Pulmonary ventilation (VE) and gas exchange were measured breath-by-breath each minute. The average of VO2 values obtained during the last 2 min of exercise for both exercise sessions was used in polynomial random coefficient regression analysis. RESULTS: In the polynomial random coefficient regression analysis for walking speeds only, both linear (r = 0.31, P = 0.053) and quadratic (r = 0.35, P = 0.029) coefficients were modestly correlated with VO2peak. Steady-state VO2 during walking at 3.0 and 4.0 mph and running at 6.0 mph was also modestly correlated with VO2peak (r = 0.30-0.48). CONCLUSIONS: The results confirm our hypothesis and suggest that, as walking speed increases, the increase in VO2 is positively correlated with the VO2peak. Our findings are consistent with the notion that cardiorespiratory fitness and exercise economy are inversely related. PMID- 20351593 TI - Biomechanical properties of concussions in high school football. AB - INTRODUCTION: Sport concussion represents the majority of brain injuries occurring in the United States with 1.6-3.8 million cases annually. Understanding the biomechanical properties of this injury will support the development of better diagnostics and preventative techniques. METHODS: We monitored all football related head impacts in 78 high school athletes (mean age = 16.7 yr) from 2005 to 2008 to better understand the biomechanical characteristics of concussive impacts. RESULTS: Using the Head Impact Telemetry System, a total of 54,247 impacts were recorded, and 13 concussive episodes were captured for analysis. A classification and regression tree analysis of impacts indicated that rotational acceleration (95582.3 rad.s-2), linear acceleration (996.1g), and impact location (front, top, and back) yielded the highest predictive value of concussion. CONCLUSIONS: These threshold values are nearly identical with those reported at the collegiate and professional level. If the Head Impact Telemetry System were implemented for medical use, sideline personnel can expect to diagnose one of every five athletes with a concussion when the impact exceeds these tolerance levels. Why all athletes did not sustain a concussion when the impacts generated variables in excess of our threshold criteria is not entirely clear, although individual differences between participants may play a role. A similar threshold to concussion in adolescent athletes compared with their collegiate and professional counterparts suggests an equal concussion risk at all levels of play. PMID- 20351595 TI - Three percent hypohydration does not affect threshold frequency of electrically induced cramps. AB - PURPOSE: Dehydration is hypothesized to cause exercise-associated muscle cramps. The theory states that dehydration contracts the interstitial space, thereby increasing the pressure on nerve terminals and cramps ensue. Research supporting this theory is often observational, and fatigue is rarely controlled. Inducing cramps with electrical stimulation minimizes many of the confounding factors associated with exercise-induced cramps (e.g., fatigue, metabolites). Thus, our goal was to minimize fatigue and determine whether hypohydration decreases the electrical stimuli required to elicit cramping (termed "threshold frequency"). METHODS: Ten males cycled for 30-min bouts with their nondominant leg at 41 degrees C and 15% relative humidity until they lost ~3% of their body mass (~2 h). Dominant leg flexor hallucis brevis muscle cramps were induced before and after hypohydration, and threshold frequency was recorded. Plasma osmolality (OSMp) characterized hydration status. Total sweat electrolytes (Na+, K+, Mg2+, and Ca2+) lost during exercise was calculated. Subjects repeated the protocol 1 wk later. RESULTS: Subjects were hypohydrated after exercise (preexercise OSMp = 282.5 T 1 mOsm.kg-1 H2O, postexercise OSMp = 295.1 +/- 1 mOsm.kg-1 H2O, P < 0.001). Subjects lost 3.0% +/- 0.1% of their body mass, 144.9 +/- 9.8 mmol of Na+, 11.2 +/- 0.4 mmol of K+, 3.3 +/- 0.3 mmol of Mg2+, and 3.1 +/- 0.1 mmol of Ca2+. Mild hypohydration with minimal neuromuscular fatigue did not affect threshold frequency (euhydrated = 23.7 +/- 1.5 Hz, hypohydrated = 21.3 +/- 1.4 Hz; F1,9 = 2.81, P = 0.12). CONCLUSIONS: Mild hypohydration with minimal neuromuscular fatigue does not seem to predispose individuals to cramping. Thus, cramps may be more associated with neuromuscular fatigue than dehydration/electrolyte losses. Health care professionals may have more success preventing exercise-associated muscle cramp by focusing on strategies that minimize neuromuscular fatigue rather than dehydration. However, the effect of greater fluid losses on cramp threshold frequency is unknown and merits further research. PMID- 20351594 TI - Effect of quadriceps strength and proprioception on risk for knee osteoarthritis. AB - PURPOSE: Impaired quadriceps strength and joint position sense (JPS) have been linked with knee osteoarthritis (OA) cross-sectionally. Although neither has been independently associated with incident radiographic OA, their combination may mediate risk. The purpose of this study was to determine whether better sensorimotor function protects against the development of incident radiographic or symptomatic knee OA. METHODS: The Multicenter Osteoarthritis study is a longitudinal study of adults aged 50-79 yr at high risk for knee OA. Participants underwent bilateral, weight-bearing, fixed-flexion radiographs, JPS acuity tests, and isokinetic quadriceps strength tests. The relationships between combinations of the tertiles of sex-specific baseline peak strength and mean JPS and development of incident radiographic (Kellgren-Lawrence (KL) grade Q2) or symptomatic knee OA (KL grade Q2 and frequent knee pain or stiffness) at a 30 month follow-up were evaluated. Secondary analyses defined JPS as the variance during the 10 JPS trials and also assessed the interaction of strength and JPS in predicting each outcome. RESULTS: The study of incident radiographic knee OA included 1390 participants (age = 61.2 +/- 7 .9 yr and body mass index = 29.4 +/- 5.1 kg.m-2), and the study of incident symptomatic knee OA included 1829 participants (age = 62.2 +/- 8.0 yr and body mass index = 30.0 +/- 5.4 kg.m-2). Greater strength at baseline protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile. There was no significant relationship between the strength-JPS interaction and the development of radiographic or symptomatic knee OA. CONCLUSIONS: The finding that quadriceps strength protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile suggests that strength may be more important than JPS in mediating risk for knee OA. PMID- 20351596 TI - Training with low muscle glycogen enhances fat metabolism in well-trained cyclists. AB - PURPOSE: To determine the effects of training with low muscle glycogen on exercise performance, substrate metabolism, and skeletal muscle adaptation. METHODS: Fourteen well-trained cyclists were pair-matched and randomly assigned to HIGH- or LOW-glycogen training groups. Subjects performed nine aerobic training (AT; 90 min at 70% VO2max) and nine high-intensity interval training sessions (HIT; 8 * 5-min efforts, 1-min recovery) during a 3-wk period. HIGH trained once daily, alternating between AT on day 1 and HIT the following day, whereas LOW trained twice every second day, first performing AT and then, 1 h later, performing HIT. Pretraining and posttraining measures were a resting muscle biopsy, metabolic measures during steady-state cycling, and a time trial. RESULTS: Power output during HIT was 297 +/- 8 W in LOW compared with 323 +/- 9 W in HIGH (P < 0.05); however, time trial performance improved by ~10% in both groups (P < 0.05). Fat oxidation during steady-state cycling increased after training in LOW (from 26 +/- 2 to 34 +/- 2 MUmol.kg-1.min-1, P < 0.01). Plasma free fatty acid oxidation was similar before and after training in both groups, but muscle-derived triacylglycerol oxidation increased after training in LOW (from 16 +/- 1 to 23 +/- 1 MUmol.kg-1.min-1, P < 0.05). Training with low muscle glycogen also increased beta-hydroxyacyl-CoA-dehydrogenase protein content (P < 0.01). CONCLUSIONS: Training with low muscle glycogen reduced training intensity and, in performance, was no more effective than training with high muscle glycogen. However, fat oxidation was increased after training with low muscle glycogen, which may have been due to the enhanced metabolic adaptations in skeletal muscle. PMID- 20351597 TI - Polysialic acid affects pathophysiological consequences of status epilepticus. AB - Modulation of the neural cell adhesion molecule by the attachment of polysialic acid residues through the polysialyl-transferase, ST8SiaIV, regulates neuronal plasticity and affects cellular alterations in the epileptic brain. Here, we determined the impact of ST8SiaIV deficiency on the pathophysiological consequences of status epilepticus (SE). ST8SiaIV deficiency reduced the latency to SE induction and increased SE-mediated mortality. Analysis of the doublecortin expression showed a reduced number of neuroblasts as a long-term consequence of SE in ST8SiaIV knockouts. Testing in a battery of different behavioral paradigms indicated that loss of ST8SiaIV affects the long-term behavioral consequences. In summary, the data suggest that the polysialic acid-neural cell adhesion molecule system is a putative target for the modulation of pathophysiological events and affects psychiatric comorbidities in epilepsies. PMID- 20351598 TI - Development and evaluation of QSPECT open-source software for the iterative reconstruction of SPECT images. AB - OBJECTIVE: In this study open-source software (QSPECT) suitable for the iterative reconstruction of single-photon emission computed tomography (SPECT) data is presented. QSPECT implements maximum likelihood expectation maximization and ordered subsets expectation maximization algorithms in a user-friendly graphical interface. The software functionality is described and validation results are presented. METHODS: Maximum likelihood expectation maximization and ordered subsets expectation maximization algorithms are implemented in C++. The Qt toolkit, a standard C++ framework for developing high-performance cross-platform applications, has been used for the graphical user interface development. QSPECT is tested using original projection data from two clinical SPECT systems: (i) APEX SPX-6/6HR and (ii) Millennium MG. Phantom experiments were carried out to evaluate the quality of reconstructed images in terms of (i) spatial resolution, (ii) sensitivity to activity variations, and (iii) the presence of scatter media. A cardiac phantom was used to simulate a normal and abnormal scenario. Finally, clinical cardiac SPECT images were reconstructed. In all cases, QSPECT results were compared with the clinical systems reconstruction software that uses the standard filtered backprojection algorithm. RESULTS: The reconstructed images show that QSPECT, when compared with standard clinical reconstruction, provides images with higher contrast, reduced background, and better separation of small sources located in small distances. In addition, reconstruction with QSPECT provides more quantitative images, and reduces the background created by scatter media. Finally, the phantom and clinical cardiac images are reconstructed with similar quality. CONCLUSION: QSPECT is a freely distributed, open-source standalone application that provides real-time, high-quality SPECT images. The software can be further modified to improve reconstruction algorithms, and include more correction techniques, such as, scatter and attenuation correction. PMID- 20351599 TI - Can 18F-FDG-PET response during radiotherapy be used as a predictive factor for the outcome of head and neck cancer patients? AB - OBJECTIVES: We investigated if (18F) fluoro-2-deoxy-D-glucose positron emission tomography (F-FDG-PET) during radiotherapy or concurrent chemoradiotherapy adds information about the treatment outcome compared with an FDG-PET study before treatment. METHODS: Forty-three patients with head and neck cancer were treated with helical tomotherapy. F-FDG-PET was performed at baseline and during the treatment after 47 Gy. Tracer accumulation at the tumor site was assessed visually and semiquantitatively using the maximal standardized uptake values (SUV(max)). With median SUV(max) of both the studies as cutoff, patients were categorized into low and high SUV(max) groups. For visual analysis, two independent observers classified patients as complete metabolic responders (CMR) or noncomplete metabolic responders (NCMR). RESULTS: At baseline the median SUV(max) was 8.11 (2.41-15.13). The overall survival (OS) and disease-free survival (DFS) were 81 and 67% versus 50 and 40% for the low and high SUV(max), respectively. OS was significantly different (P=0.027). During therapy, median SUV(max) was 4.03 (1.94-7.58). OS and DFS were 82 and 63%, versus 47 and 42% for the low and high SUV(max) group, respectively. OS was significantly different (P=0.026). No significant differences between CMR versus NCMR in OS (72 vs. 60%), and DFS (56 vs. 49%) were found. CONCLUSION: Categorizing patients on the basis of a semiquantitative approach resulted in significant differences in OS for both the scans before and during therapy. Future work on a larger number of patients is warranted to determine SUV(max) cutoff values which could be used for the early identification of patients with poor treatment outcome or perhaps other therapeutic approaches. PMID- 20351601 TI - Effect of contact lens wear and a near task on tear film break-up. AB - PURPOSE: To study the effect of extrinsic controls on blinking by examining blink parameters and tear stability among adapted soft contact lens (CL) wearers performing tasks that require varying amounts of visual concentration. METHODS: The Demographic Questionnaire, Contact Lens Dry Eye Questionnaire, and Current Symptoms Questionnaire were completed by 15 adapted soft CL wearers (nine females). Three 55 s simultaneous measurements of tear film stability via retroillumination and blinking were obtained with a slit-lamp biomicroscope and 200 Hz video camera while subjects listened to music and played a video game with and without their habitual CLs. Interblink interval (IBI) and blink amplitude (BA) were calculated. The area of break-up (AB) was calculated for the retroillumination image before each blink. The Current Symptoms Questionnaire was completed four times throughout testing. RESULTS: With the game compared to music, IBI was significantly longer and BA significantly decreased without CLs (p < or = 0.001). With CLs, the IBI did not significantly change between tasks but the BA significantly decreased (p = 0.100). The AB significantly increased with CL and the game (paired t-test, p < or = 0.001). The BA was significantly correlated with self-reported severity of dry eye for all testing scenarios (Spearman r > or = 0.5579, p < 0.0001) and several symptom measures (Spearman r > or = 0.6262, p < 0.0001). The AB was significantly correlated with symptom measures including bothersome discomfort for the game with and without CLs (Spearman r > or = 0.5064, p < 0.0001). CONCLUSIONS: During tasks requiring concentration, the IBI increased (blink rate decreased) and many blinks were incomplete without CLs. With CLs, tear film instability increased. Blinking frequency also increased, but it remained high when subjects played the game, and symptoms of ocular irritation increased. This suggests that wearing soft CLs, even when fully adapted, provides enough extrinsic ocular surface stimulation to override internal controls and affect blink parameters. PMID- 20351600 TI - Visual impact of Zernike and Seidel forms of monochromatic aberrations. AB - PURPOSE: The aim of this study was to examine the impact of different aberrations modes (e.g., coma, astigmatism, spherical aberration [SA]) and different aberration basis functions (Zernike or Seidel) on visual acuity (VA). METHODS: Computational optics was used to generate retinal images degraded by either the Zernike or Seidel forms of second through fourth-order aberrations for an eye with a 5-mm pupil diameter. High contrast, photopic VA was measured using method of constant stimuli for letters displayed on a computer-controlled, linearized, quasimonochromatic (lambda = 556 nm) display. RESULTS: Minimum angle of resolution (MAR) varied linearly with the magnitude (root mean square error) of all modes of aberration. The impact of individual Zernike lower- and higher-order aberrations (HOAs) varied significantly with mode, e.g., arc minutes of MAR per micrometer of root mean square slopes varied from 7 (spherical defocus) to 0.5 (quadrafoil). Seidel forms of these aberrations always had a smaller visual impact. Notably, Seidel SA had 1/17th the impact of Zernike SA with the same wavefront variance, and about 1/4th the impact of Zernike SA with matching levels of r wavefront error. With lower-order components removed, HOAs near the center of the Zernike pyramid do not have a large visual impact. CONCLUSIONS: The majority of the visual impact of high levels of fourth-order Zernike aberrations can be attributed to the second-order terms within these polynomials. Therefore, the impact of SA can be minimized by balancing it with a defocus term that flattens the central wavefront (paraxial focus) or maximizes the area of the pupil with a flat wavefront. Over this wide range of aberration types and levels, image quality metrics based on the Point Spread Function (PSF) and Optical Transfer Function (OTF) can predict VA as reliably as VA measures can predict retests of VA, and, thus, such metrics may become valuable predictors of both VA and, via optimization, refractions. PMID- 20351602 TI - Amblyopia in astigmatic infants and toddlers. AB - PURPOSE: To determine whether reduced astigmatism-corrected acuity for vertical (V) and/or horizontal (H) gratings and/or meridional amblyopia (MA) are present before 3 years of age in children who have with-the-rule astigmatism. METHODS: Subjects were 448 children, 6 months through 2 years of age with no known ocular abnormalities other than with-the-rule astigmatism, who were recruited through Women, Infants and Children clinics on the Tohono O'odham reservation. Children were classified as non-astigmats (< or =2.00 diopters) or astigmats (>2.00 diopters) based on right eye non-cycloplegic autorefraction measurements (Welch Allyn SureSight). Right eye astigmatism-corrected grating acuity for V and H stimuli was measured using the Teller Acuity Card procedure while children wore cross-cylinder lenses to correct their astigmatism or plano lenses if they had no astigmatism. RESULTS: Astigmatism-corrected acuity for both V and H gratings was significantly poorer in the astigmats than in the non-astigmats, and the reduction in acuity for astigmats was present for children in all three age groups examined (6 months to <1 year, 1 to <2 years, and 2 to <3 years). There was no significant difference in V-H grating acuity (no evidence of MA) for the astigmatic group as a whole, or when data were analyzed for each age group. CONCLUSIONS: Even in the youngest age group, astigmats tested with astigmatism correction showed reduced acuity for both V and H gratings, which suggests that astigmatism is having a negative influence on visual development. We found no evidence of orientation-related differences in astigmatism-corrected grating acuity, indicating either that MA does not develop before 3 years of age, or that most of the astigmatic children had a type of astigmatism, i.e., hyperopic, that has proven to be less likely than myopic or mixed astigmatism to result in MA. PMID- 20351604 TI - Vascular pulsations on impedance audiometry as a sign of a third-mobile window lesion. AB - OBJECTIVE: Description of a new audiometric sign of a third-mobile window lesion. PATIENTS: Subject with known superior canal dehiscence. INTERVENTION(S): Diagnostic. MAIN OUTCOME MEASURE(S): Results of impedance audiometry testing. RESULTS: Vascular pulsations seen on impedance audiometry on dehiscent side. CONCLUSION: Vascular pulsations seen on impedance audiometry may indicate a third mobile window lesion in the inner ear. PMID- 20351603 TI - Passive cigarette smoke exposure and soft contact lens wear. AB - PURPOSE: To prospectively investigate the effects of passive cigarette smoke exposure on the ocular surface and tear film in soft contact lens (SCL) wearers. METHODS: Twelve right eyes of 12 SCL wearers without any ocular or systemic diseases and 10 right eyes of 10 subjects who never wore CLs were examined before and 2 h after 5 min of passive cigarette smoke exposure in a controlled smoke chamber. Tear evaporation rate measurement, tear film break-up time (TBUT) examination, ocular surface fluorescein, rose bengal stainings, and Schirmer I test were performed at each visit. RESULTS: The mean tear evaporation rates, TBUTs, and vital staining scores were significantly worse in CL wearers compared with healthy control subjects. TBUTs showed significant worsening after passive smoke exposure in both groups. The mean tear evaporation rate and vital staining scores showed a significant increase with brief passive smoke exposure in subjects not wearing CLs but not in CL wearers. CONCLUSION: Even brief passive exposure to cigarette smoke is associated with adverse effects on the ocular surface as evidenced by an increase in tear instability and damage to the ocular surface epithelia in SCL wearers and non-CL wearers. PMID- 20351605 TI - Endolymphatic sac tumors in von Hippel-Lindau disease: report of three cases. AB - OBJECTIVES: To illustrate the diagnostic and pathophysiologic issues of endolymphatic sac tumors (ELSTs) and its clinical association with von Hippel Lindau (VHL) disease and to demonstrate the interest of genetic testing in such cases. STUDY DESIGN: Retrospective analysis of 3 cases of ELST with VHL in 3 different clinical and prognostic situations. MAIN OUTCOMES: The first case was diagnosed on the concomitant finding of a central nervous system lesion. The familial genetic testing revealed the presence of the VHL mutation in an asymptomatic daughter, which justified regular follow-up. In the second case of known VHL syndromic disease, the pathophysiologic role of the endolymphatic sac was questioned, with vertigo as the initial, unique symptom of ELST. In the third case, a giant hypervascularized ELST, initially diagnosed as jugular paraganglioma, was the unique manifestation of VHL disease. The young age of the patient could explain the absence of other tumors. CONCLUSION: Diagnosis of ELSTs may be difficult especially when the original site of the lesion cannot be clearly identified. Such tumors may be revealed or may develop with VHL disease. On presentation of a lytic, vascularized tumor of the posterior face of the petrous bone, clinicians should systematically search for other manifestations of VHL disease and propose a VHL genetic testing for patients, and relatives in case of a positive test, to detect early asymptomatic other tumors. The type of VHL mutation might predict the aggressiveness. PMID- 20351606 TI - Frequency and location of synkineses in patients with peripheral facial nerve paresis. AB - BACKGROUND: Synkinesis is an involuntary movement accompanying a voluntary one. These unintentional movements are caused by an undifferentiated regeneration of the facial nerve that occurs after being compressed or partially damaged. Synkinesis can affect eating, drinking, and speaking and can be socially distressing because of facial asymmetry and disruption of intended emotional expressions. OBJECTIVE: This study aims to describe the frequency and location of synkinesis in patients with peripheral facial nerve paresis. METHODS: Patients were observed on video and analyzed using a standardized Synkinesis Scoring Form. Five voluntary expressions, derived from the Sunnybrook Facial Grading Scale, were tested: brow lift, eye closure, smile, snarl, and lip pucker. The Kruskal Wallis test, 95% confidence intervals, and analysis of variance were used to analyze data. RESULTS: Patients with a facial nerve paresis (n = 103) were observed, and all showed synkineses. Lifting-mouth-corner-synkinesis coupled to voluntary brow lift movements (89%) or eye closure (85%) occurred most frequently. The voluntary movement lip puckering evoked the most synkineses of the eye (narrowing, 82%). During all voluntary expressions lifting-brow synkineses occurred the least (17%). A significant effect for sex and age (p < 0.05) was found but not for side and duration of the paresis (p > 0.05). CONCLUSION: Mouth-corner-synkinesis is most common in brow lift and eye movements, whereas eye synkinesis is coupled to mouth movements. These are important facts for rehabilitation of facial nerve pareses, to refine and intensify the inhibition and control of synkineses so that facial symmetry and expressions may improve. PMID- 20351607 TI - Is electric acoustic stimulation better than conventional cochlear implantation for speech perception in quiet? AB - OBJECTIVE: To assess whether combined electric acoustic stimulation (EAS) provides a significant hearing-in-quiet advantage over ipsilateral electrical stimulation alone, ipsilateral acoustic stimulation alone, or full-length cochlear implantation without preserved hearing. SETTING: Tertiary care academic referral center. PATIENTS: Two matched groups of cochlear implant (CI) patients that were implanted with either an EAS or full-length device and use similar speech processing strategies. INTERVENTION: EAS cochlear implantation and hearing preservation (n = 10, EAS group) or conventional CI (n = 10, conventional CI group) without hearing preservation. MAIN OUTCOME MEASURES: Status of residual hearing and speech perception data in quiet at 3 and 6 months after fitting. RESULTS: Preoperatively, the mean aided Consonant Nucleus Consonant Word Test word score was 24.2 +/- 8.3% for the EAS group and 20.7 +/- 11.36% for the conventional CI group (p = 0.14). In the conventional CI group, hearing was not preserved after surgery in any subject, whereas 9 of the 10 subjects in the EAS group had hearing preservation. Mean CNC word scores at 6 months after activation using electrical stimulation alone were 50.3 +/- 11.53% in the EAS group and 53.8 +/- 17.32% in the conventional CI group (p = 0.81). Between-condition comparisons among the EAS subjects revealed that combined stimulation was significantly better than either the electrical or acoustic stimulation condition alone (p < 0.05). When compared with the conventional CI group, combined stimulation in EAS subjects was again superior (p < 0.05). CONCLUSION: Limited length CI with ipsilateral hearing preservation provides comparable speech perception performance results to conventional CI when electric stimulation alone is used. The addition of ipsilateral acoustic stimulation in ears with preserved residual hearing provides an additional benefit over electrical stimulation alone. PMID- 20351608 TI - Functional study of mucus secretion of the eustachian tube in Guinea pigs. AB - OBJECTIVES: Our aim was to verify neural regulation of submucous gland mucus secretions in the Eustachian tubes of guinea pigs. STUDY DESIGN: Prospective animal study. METHODS: Eustachian tubes harvested from 12 guinea pigs were used for this study. For real-time resolution of pure glandular secretion, we used a modified method of single-gland optical measurement. Secretory monitoring was undertaken after each preparation with phenylephrine, isoproterenol, forskolin, and substance P. To confirm the viability of each tissue, we examined glandular secretion after treatment with carbachol. Secretory effects of each agonist were evaluated by comparing with basal secretion using a Student's t test (p < 0.01). RESULTS: The Ca-elevating agonists carbachol and substance P showed greater effects on submucous gland secretions of the Eustachian tube than the cyclic adenosine monophosphate (cAMP)-elevating agonists forskolin and isoproterenol. However, phenylephrine, although it belongs to the Ca-elevating agonist group, did not show any significant secretory effect. CONCLUSION: The optical measurement method used in this study had the merit of real-time resolution of submucous glandular secretion. Submucous glandular secretion in the Eustachian tube was regulated by both Ca- and cAMP-elevating agonists, and Ca-elevating agonists seemed to be more potent than cAMP-elevating agonists except phenylephrine. Our results suggest that not only the autonomic nerve system but also the neuropeptides such as substance P are closely related to glandular secretion in the Eustachian tube, and beta-adrenergic receptors seem to be more related to submucous glandular secretion of the Eustachian tube in guinea pig than alpha-adrenergic receptors. PMID- 20351609 TI - Craniometaphyseal dysplasia-induced hearing loss. PMID- 20351610 TI - Inverted papilloma of the middle ear. PMID- 20351611 TI - Geniculate ganglion hemangiomas: clinical results and long-term follow-up. AB - OBJECTIVE: To review the clinical presentation, evaluation, and management of 18 patients with geniculate ganglion hemangiomas seen at the House Clinic. STUDY DESIGN: Retrospective case review. SETTING: Private neurotological tertiary referral center. PATIENTS: Eighteen patients with geniculate ganglion hemangiomas treated at the House Clinic between 1986 and 2008. INTERVENTION: Observation or surgical intervention using the middle fossa or translabyrinthine craniotomy for decompression or excision of the hemangioma with or without facial nerve resection and grafting. MAIN OUTCOME MEASURES: Postoperative facial function using the House-Brackmann grading system, postoperative audiograms and postoperative follow-up magnetic resonance imaging or computed tomographic scan of the temporal bone. RESULTS: Approximately 13 patients (72%) were female subjects, and 5 (28%) were male subjects. Mean age was 54 years, and follow-up was 73 months. 17 (94%) of 18 patients presented with facial paresis or paralysis. Facial twitching was present in 10 (56%) of 18 cases. Four patients (22%) presented with hearing loss. Facial nerve function was House-Brackmann grade I/II in 7(38%), III/IV in 5 (28%), and V/VI in 6 (34%) patients, respectively. Approximately 13 patients (72%) underwent middle fossa craniotomy for excision or decompression of their hemangiomas, and 2 (11%) underwent translabyrinthine removal. The facial nerve was preserved in 11 (73%) of 15 patients and was excised and grafted in 4 (27%) of 15. Recovery to a House Brackmann grade I/II was seen in 8 (72%) of 11 patients in whom the integrity of the facial nerve was preserved. In the surgical group, hearing remained stable in 64% of hearing preservation cases and worsened in 38%. Facial function remained stable in the nonsurgical group. CONCLUSION: Geniculate ganglion hemangiomas are rare vascular malformations that produce facial paralysis despite their relative small size at presentation. When possible, excision with neural preservation yields better long-term facial function. Recurrences are rare. PMID- 20351612 TI - Cholesterol granuloma of the petrous apex. PMID- 20351613 TI - Secretory phospholipase A2 pathway during pediatric acute respiratory distress syndrome: a preliminary study. AB - OBJECTIVE: To verify if secretory phospholipase A2 (sPLA2) is increased in pediatric acute respiratory distress syndrome (ARDS) triggered or not by respiratory syncytial virus infection and to clarify how the enzyme may influence the disease severity and the degree of ventilatory support. DESIGN: Prospective pilot study. SETTING: Two academic pediatric intensive care units. PATIENTS: All infants < 6 months old hospitalized for severe respiratory syncytial virus bronchiolitis, who developed ARDS (respiratory syncytial virus-ARDS group); all infants < 6 months old diagnosed with ARDS secondary to other causes (ARDS group); and infants < 6 months old who needed ventilation for reasons other than any lung disease (control group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled six respiratory syncytial virus -ARDS babies, five ARDS babies, and six control infants. The sPLA2 activity and tumor necrosis factor (TNF)-alpha were significantly higher in the bronchoalveolar lavage of ARDS infants. Worst oxygenation, ventilation, and longer pediatric intensive care unit stay and ventilation time were present in ARDS babies. No differences were found in Clara cell secretory protein and in serum cytokines levels. Because there is no correlation between bronchoalveolar lavage protein content (a marker of permeability) and sPLA2, the enzyme seems mainly produced in the alveoli. TNF alpha, the main inductor of sPLA2 expression, significantly correlates with the enzyme level in the bronchoalveolar lavage. Significant positive correlations exist between sPLA2, TNF-alpha and oxygen need, mean airway pressure, ventilatory index, and the Murray's lung injury score. Negative correlations were also found between sPLA2, TNF-alpha, and Pao2/Fio2 ratio. CONCLUSIONS: The sPLA2 and TNF alpha are increased in ARDS and seem correlated with clinical severity, higher oxygen requirement, and more aggressive ventilation. This correlation confirms findings from adult experience and should guide further investigations on pediatric ARDS pathophysiology. PMID- 20351614 TI - Variation in duration of respiratory support among Australian and New Zealand pediatric intensive care units. AB - OBJECTIVE: To test if there was significant variation of mean adjusted duration of respiratory support (RS) at the site level among Australian and New Zealand pediatric intensive care units (PICUs) and to determine whether the pattern of variation differed from the site-level pattern of variation in length of stay (LoS). DESIGN: Separate outcome prediction models for estimating PICU LoS and duration of RS were constructed, using patient data collected between 2002 and 2007. Gamma regression was used to model LoS for all admissions included in the study population, and log normal regression was used to model duration of RS for the subset of patients receiving RS. For both models, case-mix adjustment was achieved by entering patient risk factors as fixed effects, and the PICU or site of care was entered as a random effect. SETTING: Data for 31,358 admissions were collected from nine specialist PICUs in Australia and New Zealand. MEASUREMENTS AND MAIN RESULTS: Average risk-adjusted duration of RS and LoS for each PICU. There was significant unit-level variation in the adjusted mean LoS and duration of RS among PICUs in Australia and New Zealand. One site had a mean duration of RS that was significantly longer than expected, whereas two sites had a mean duration of RS that was significantly shorter than expected at the 95% level. Unit-level variation in duration of RS is consistent with unit-level variation in LoS for six PICUs and significantly different in two units. CONCLUSION: There is unit-level variation in LoS and duration of RS, not accounted for by case-mix. Concurrent analysis of unit-level variation in LoS and duration of RS can help to identify differences in discharge practice and provide direction for improvements in clinical or administrative efficiency. PMID- 20351616 TI - Genetic variability in complement activation modulates the systemic inflammatory response syndrome in children. AB - OBJECTIVE: To determine the impact of genetic variability in complement activation on early development of the systemic inflammatory response syndrome (SIRS) in general pediatric critical care. DESIGN: Prospective, observational, cohort study. SETTING: A tertiary pediatric intensive care unit in the United Kingdom. PATIENTS: Children with at least one organ failure expected to stay in the intensive care unit >12 hrs, or an expected death within 12 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 299 children were genotyped for functional polymorphisms in the complement activation cascade. We identified complement factor H as an important independent genetic modifier of SIRS/sepsis. Homozygosity for the complement factor H Y402H polymorphism, which is thought to reduce complement inhibition, was associated with less frequent SIRS/sepsis (the adjusted odds ratio for the homozygous variant complement factor H Y402H [CC] carriers was 0.3, 95% confidence interval, 0.1-0.7, p = .005). We also confirmed that structural and promoter variant mannose-binding lectin genotypes are a risk factor for SIRS/sepsis in pediatric critical care (adjusted odds ratio, 2.5; 95% confidence interval, 1.3-5.0, p = .008). Both findings were independent of clinical characteristics and other potentially confounding genetic polymorphisms in the innate immune system. CONCLUSIONS: Functional polymorphisms in the complement activation cascade modify the risk for early SIRS/sepsis in general pediatric critical care. The complement factor H Y402H variant allele is protective, whereas the mannose-binding lectin variant polymorphisms increase risk. A genotype that permits vigorous complement activation to an infectious or inflammatory insult may offer protection from development of systemic inflammation. PMID- 20351615 TI - Daily practice of mechanical ventilation in Italian pediatric intensive care units: a prospective survey. AB - OBJECTIVES: To assess how children requiring endotracheal intubation are mechanically ventilated in Italian pediatric intensive care units (PICUs). DESIGN: A prospective, national, observational, multicenter, 6-month study. SETTING: Eighteen medical-surgical PICUs. PATIENTS: A total of 1943 consecutive children, aged 0-16 yrs, admitted between November 1, 2006 and April 30, 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on cause of respiratory failure, length of mechanical ventilation (MV), mode of ventilation, use of specific interventions were recorded for all children requiring endotracheal intubation for >24 hrs. Children were stratified for age, type of patient, and cause of respiratory failure. A total of 956 (49.2%) patients required MV via an endotracheal tube; 673 (34.6%) were ventilated for >24 hrs. The median length of MV was 4.5 days for all patients. If postoperative patients were excluded, the median time was 5 days. Bronchiolitis (6.7%), pneumonia (6.7%), and upper airway obstruction (5.3%) were the most frequent causes of acute respiratory failure, and altered mental status (9.2%) was the most frequent reason for MV. The overall mortality was 6.7% with highest rates for heart disease (nonoperative), sepsis, and acute respiratory distress syndrome (26.1%, 22.2%, and 16.7% respectively). Length of stay, associated chronic disease, severity score on admission, and PICU mortality were significantly higher in children who received MV (p < .05) than in children who did not. Controlled MV and pressure support ventilation + synchronized intermittent mandatory ventilation were the most frequently used modes of ventilatory assistance during PICU stay. CONCLUSIONS: Mechanical ventilation is frequently used in Italian PICUs with almost one child of two requiring endotracheal intubation. Children treated with MV represent a more severe category of patients than children who are breathing spontaneously. Describing the standard care and how MV is performed in children can be useful for future clinical studies. PMID- 20351617 TI - Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. AB - OBJECTIVE: To determine the independent impact of acute kidney injury (AKI) and renal replacement therapy (RRT) in infants and children who receive extracorporeal membrane oxygenation. Despite continued expertise/technological advancement, patients who receive extracorporeal membrane oxygenation have high mortality. AKI and RRT portend poor outcomes independent of comorbidities and illness severity in several critically ill populations. DESIGN: Retrospective cohort study. The primary variables explored are AKI (categorical complication code for serum creatinine > 1.5 mg/dL or International Statistical Classification of Diseases and Related Health Problems, Revision 9 for acute renal failure), and RRT (complication/Current Procedural Terminology code for dialysis or hemofiltration). Multiple variables previously associated with mortality in this population were controlled, using logistic stepwise regression. Decision tree modeling was performed to determine optimal variables and cut points to predict mortality. PATIENTS: Critically ill neonates (0-30 days old) and children (> 30 days but < 18 yrs old) in the Extracorporeal Life Support Organization registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neonatal mortality was 2175 (27.4%) of 7941. Nonsurvivors experienced more AKI (413 [19%] of 2175 vs. 225 [3.9%] of 5766, p < .0001), and more received RRT (863 [39.7%] of 2175 vs. 923 [16.0%] of 5766, p < .0001) than survivors. Pediatric mortality was 816 (41.6%) of 1962. Pediatric nonsurvivors similarly experienced more AKI (264 [32.3%] of 816 vs. 138 [12.0%] of 1146, p < .0001) and RRT (487 [58.9%] of 816 vs. 353 [30.8%] of 1146, p < .0001) than survivors. After adjusting for confounding variables, the adjusted odds ratio for neonatal group was 3.2 (p < .0001) post AKI and 1.9 (p < .0001) given RRT. Similarly, the pediatric adjusted odds ratio for mortality was 1.7 (p < .001) post AKI and 2.5 (p < .0001) given RRT. AKI and RRT were essential in the neonatal and pediatric mortality decision trees. CONCLUSIONS: After adjusting for known predictors of mortality, AKI and RRT independently predict mortality in neonates and children, who receive extracorporeal membrane oxygenation. Ascertainment of AKI risk factors, testing novel therapies, and optimizing the timing/delivery of RRT may positively impact survival. PMID- 20351618 TI - Respiratory viruses in nepalese children with and without pneumonia: a case control study. AB - BACKGROUND: The causative role of respiratory viruses detected in upper airway secretions in childhood pneumonia needs further investigation. OBJECTIVE: To measure the association between infection with respiratory RNA viruses and pneumonia in children. METHODS: From March 2006 to July 2007, we conducted a case control study of 680 pneumonia cases (WHO criteria) and 680 randomly selected, concurrently sampled age-matched controls among children aged 2-35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each child was examined for 7 respiratory viruses using reverse transcription polymerase chain reaction. We calculated the matched odds ratios (MORs) for the detection of the individual viruses from a case compared with a control as measures of pathogenicity using conditional logistic regression. RESULTS: At least 1 virus was recovered in 248 (36.5%) cases and 48 (7.1%) controls. The MOR varied from 2.0 to 13.0; the highest associations were observed for parainfluenza virus type 3 (MOR 13.0; 95% confidence interval [CI] 6.0-28.0), respiratory syncytial virus (MOR 10.7; CI 4.6 24.6), and influenza A (MOR 6.3; CI 1.9-21.4). We observed that the association was lower for children age 2-5 months compared with older children for parainfluenza virus type 3 (P value for interaction 0.002). CONCLUSIONS: All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia. PMID- 20351619 TI - Optical coherence tomography after pars plana vitrectomy for retinal detachment related to choroidal coloboma. AB - PURPOSE: The purpose was to study the anatomical outcome of choroidal coloboma with retinal detachment managed by pars plana vitrectomy with silicone oil tamponade using optical coherence tomography. METHODS: Six eyes of six patients with retinal detachment related to choroidal coloboma underwent pars plana vitrectomy with internal tamponade using silicone oil. Pre- and postoperative best-corrected visual acuities, intraocular pressure measurements, and intra- and postoperative complications were obtained. Color fundus photographs and optical coherence tomography images were taken at each follow-up. RESULTS: Patients were observed up to a mean of 14 months (range, 8-18 months). Silicone oil was removed in all eyes. In all patients who had undergone vitrectomy, the retina was completely reattached before and after silicone oil extraction. Postoperatively, best-corrected visual acuities improved in 5 patients and remained unchanged in 1 patient ranging from 20/200 to 20/40 at the last follow-up. Although the retina was reattached in all patients, the optical coherence tomography showed a persistent intercalary membrane detachment in 4 patients (67%). In 1 patient (16%), subclinical retinal detachment that did not increase during the follow-up after silicone oil removal was detected just beyond the margin of the coloboma. CONCLUSION: After vitrectomy and silicone oil removal, optical coherence tomography showed persistent detachment of the intercalary membrane in most patients. These findings emphasize the importance of sealing the junction between the intercalary membrane and extracolobomatous retina with a laser barrier. PMID- 20351620 TI - Hepatitis B virus, hepatitis C virus and HIV coinfection among people living with HIV/AIDS in Buenos Aires, Argentina. PMID- 20351621 TI - Let Them Know: evaluation of an online partner notification service for chlamydia that offers E-mail and SMS messaging. AB - This study evaluated Let Them Know (http://www.letthemknow.org.au), an online partner notification website offering e-mail and text message notification services to individuals diagnosed with chlamydia. A substantial and increasing number of text messages were sent, pointing to the potential for improved partner notification rates. PMID- 20351623 TI - Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic resistance in an adolescent population. AB - OBJECTIVE: To determine the prevalence and incidence of trichomoniasis, risk factors for infection, and the prevalence of metronidazole and tinidazole resistant Trichomonas vaginalis (T. vaginalis) in female adolescents. METHODS: Nonpregnant, HIV-seronegative, sexually active females (13-19 years) visiting an inner city public primary care clinic were tested for T. vaginalis by wet mount and culture, and interviewed about risk-taking behavior every 6 months. Infected patients were treated with a 2 g oral dose of metronidazole. Isolates from positive T. vaginalis cultures were tested for in vitro resistance to metronidazole and tinidazole. RESULTS: Among 467 study participants, 67 (14.4%; 95% confidence interval, 11.3-17.5) were diagnosed with trichomoniasis at first T. vaginalis culture. Significant risk factors for T. vaginalis infection were having an older sex partner and concurrent Neisseria gonorrhoeae infection. The incidence was 22.1 cases per 100 person-years. Among 42 participants who had a prevalent infection and returned for followup, 13 (31.0%) had at least 1 more episode of trichomoniasis. Resistance testing was completed for 78 isolates: 37 at first visit and 41 during follow-up. One (2.7%; 95% confidence interval, 0.07 14.2) of the 37 first-visit isolates was moderately resistant to metronidazole (minimal lethal concentration = 200 microg/mL). Of the 41 follow-up visit isolates, 1 was moderately resistant to metronidazole and 2 had borderline resistance (minimal lethal concentration = 50 microg/mL). The prevalence of tinidazole resistance was 0% (0.0%-9.5%). CONCLUSION: The study population had high prevalence and incidence of trichomoniasis. The prevalence of antibiotic resistant T. vaginalis among female adolescents was low. PMID- 20351622 TI - Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2. AB - BACKGROUND: The continuation of developing Herpes simplex virus type-2 (HSV-2) prophylactic vaccines requires parallel mathematical modeling to quantify the effect on the population of these vaccines. METHODS: Using mathematical modeling we derived 3 summary measures for the population effect of imperfect HSV-2 vaccines as a function of their efficacies in reducing susceptibility (VES), genital shedding (VEP), and infectivity during shedding (VEI). In addition, we studied the population level effect of vaccine intervention using representative vaccine efficacies. RESULTS: A vaccine with limited efficacy of reducing shedding frequency (VEP = 10%) and infectivity (VEI = 0%) would need to reduce susceptibility by 75% (VES = 75%) to substantially reduce the sustainability of HSV-2 infection in a population. No reduction in susceptibility would be required to reach this target in a vaccine that decreased shedding by 75% (VES = 0%, VEP = 75%, VEI = 0%). Mass vaccination using a vaccine with imperfect efficacies (VES = 30%, VEP = 75%, and VEI = 0%) in Kisumu, Kenya, in 2010 would decrease prevalence and incidence in 2020 by 7% and 30%, respectively. For lower prevalence settings, vaccination is predicted to have a lower effect on prevalence. CONCLUSION: A vaccine with substantially high efficacy of reducing HSV-2 shedding frequency would have a desirable effect at the population level. The vaccine's short-term impact in a high prevalence setting in Africa would be a substantial decrease in incidence, whereas its immediate impact on prevalence would be small and would increase slowly over time. PMID- 20351624 TI - Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. AB - High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. d-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the d-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of d galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury. PMID- 20351625 TI - Liver volume, as assessed by four ultrasonic crystals arranged to form a tetrahedron, decreases during anaphylactic shock in anesthetized rats. AB - We determined the hepatic volume change in anaphylactic hypotension by using four ultrasonic crystals in anesthetized rats. The hepatic volume was measured with four ultrasonic crystals arranged to form a tetrahedron on the liver surface. Before in vivo experiments, using isolated perfused rat liver preparations, we compared the measured liver volume changes with the whole-liver weight changes during hepatic blood flow rate changes and venoconstriction induced by norepinephrine. The measured relative change of the tetrahedron volume (V[utc]; percentage changes of the initial volume) was closely correlated with the liver weight change (W; percentage changes of the initial liver weight): V(utc) = 0.85W - 4.11 (r2 = 0.67). Then, we measured the liver weight and the tetrahedron volume during hepatic anaphylaxis in isolated perfused liver excised from the rats sensitized with ovalbumin. An injection of the antigen into the perfusate caused anaphylactic venoconstriction, liver weight loss (1.1 +/- 0.3 g; 9% +/- 1%), and the tetrahedron volume reduction (12% +/- 4%). Finally, we measured the liver volume change during anaphylactic hypotension in anesthetized ovalbumin sensitized rats. When the antigen was i.v. injected into anesthetized rats, along with systemic hypotension and hepatic venoconstriction, the liver tetrahedron volume decreased by 6% +/- 2% from baseline. In conclusion, we established a method to measure the hepatic volume by using four ultrasonic crystals forming a tetrahedron. Using this ultrasonic crystal method, we demonstrated that liver volume decreases during anaphylactic hypotension in anesthetized rats. PMID- 20351626 TI - The indazole derivative YD-3 specifically inhibits thrombin-induced angiogenesis in vitro and in vivo. AB - Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and the inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to examine the antiangiogenic efficacy of YD-3 [1-benzyl 3(ethoxycarbonylphenyl)-indazole], a selective thrombin inhibitor, on thrombin induced endothelial cell proliferation and neoangiogenesis in a murine Matrigel model. First, the effect of YD-3 on angiogenesis was evaluated in vivo using the mouse Matrigel implant model. Plugs treated with 1 and 10 MUM of YD-3 inhibited neovascularization induced by thrombin, protease-activated receptor (PAR) 1, and PAR-4, but not by vascular endothelial growth factor, in a concentration dependent manner over 7 days. These results indicate that YD-3 has specific antiangiogenic activity on thrombin. YD-3 also inhibited (in a concentration dependent manner) the ability of thrombin, PAR-1, and PAR-4, but not PAR-2, to induce the proliferation of human umbilical vascular endothelial cells, using a [3H]thymidine incorporation assay. YD-3 predominantly inhibited thrombin-induced vascular endothelial growth factor receptor 2 (Flk-1) expression, but not extracellular signal-regulated kinase 1/2 phosphorylation, using Western blot analysis. YD-3 may have benefit in elucidating pathophysiology induced by thrombin-induced angiogenesis. PMID- 20351627 TI - Mechanisms of the beneficial effect of hypertonic saline solution in acute pancreatitis. AB - Administration of hypertonic saline (HS) solution to rats with acute pancreatitis (AP) decreases mortality and systemic inflammation. We hypothesized that these effects are related not only to systemic inflammatory reduction, but also to a reduction of the pancreatic lesion. Acute pancreatitis was induced in Wistar rats by injection of 2.5% sodium taurocholate. Animals were divided in groups: without AP, not treated AP, AP treated with NaCl 0.9%, and AP treated with NaCl 7.5%. Trypsinogen activation peptides and amylase activity were increased in ascitic fluid and serum and were not affected by treatment with HS. Pancreatic inflammation was evaluated by increased myeloperoxidase activity, malondialdehyde formation, and histopathology for severity of pancreatic lesions. The HS did not affect these parameters. Expression of cyclooxygenase 2 and inducible nitric oxide synthase was markedly increased in the pancreas of the AP group and was reduced by treatment with HS. This treatment also reduced the levels of TNF-alpha and IL-6 but not of IL-10 in the pancreatic tissue. These results show that HS modulates cytokine production and expression of enzymes responsible for inflammatory mediator production in the pancreas without affecting the severity of the pancreatic lesions. PMID- 20351628 TI - Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model. AB - Sepsis/multiple organ dysfunction syndrome is the leading cause of death in critically ill patients. Recently, it has been suggested that hydrogen gas (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical (*OH, the most cytotoxic reactive oxygen species). We have found that H2 inhalation significantly improved the survival rate and organ damage of septic mice with moderate or severe cecal ligation and puncture. In the present study, we investigated the effects of 2% H2 treatment on survival rate and organ damage in zymosan (ZY)-induced generalized inflammation model. Here, we found that 2% H2 inhalation for 60 min starting at 1 and 6 h after ZY injection, respectively, significantly improved the 14-day survival rate of ZY-challenged mice from 10% to 70%. Furthermore, ZY-challenged mice showed significant multiple organ damage characterized by the increase in serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine), as well as lung, liver, and kidney histopathological scores at 24 h after ZY injection, which was significantly attenuated by 2% H2 treatment. In addition, we found that the beneficial effects of H2 treatment on ZY-induced organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzyme, and reduced levels of early and late proinflammatory cytokines in serum and tissues. In conclusion, this study provides evidence that H2 treatment protects against multiple organ damages in ZY-induced generalized inflammation model, suggesting the potential use of H2 as a therapeutic agent in the therapy of conditions associated with inflammation-related multiple organ dysfunction syndrome. PMID- 20351643 TI - Association of factor VII gene polymorphisms with Budd Chiari syndrome. PMID- 20351629 TI - Pilot study of a (213)bismuth-labeled anti-CD45 mAb as a novel nonmyeloablative conditioning for DLA-haploidentical littermate hematopoietic transplantation. AB - BACKGROUND: A pilot study was conducted to determine whether conditioning using selective targeting of hematopoietic cells with an alpha-particle emitter, bismuth-213 ((213)Bi)-labeled anti-CD45 monoclonal antibody (mAb) is sufficient to overcome the major histocompatibility barrier in a canine model of dog leukocyte antigen-haploidentical hematopoietic cell transplantation (HCT). METHODS: Six dogs were administered 0.5 mg/kg (213)Bi-labeled anti-CD45 mAb (dose (213)Bi=2.26-4.9 mCi/kg) in six to eight injections. For postgrafting immunosuppression, all dogs received cyclosporine and mycophenolate mofetil. RESULTS: All dogs had initial donor engraftment, with three of six dogs having sustained engraftment to last point of follow-up. Two dogs receiving 2.26 and 3.25 mCi/kg of (213)Bi rejected their grafts at day +127 and +125, respectively, whereas dogs receiving (213)Bi doses of 3.3 mCi/kg or greater achieved high level donor chimerism. CONCLUSION: The results suggest that nonmyeloablative conditioning with (213)Bi-labeled anti-CD45 mAb could be applicable to major histocompatibility haploidentical HCT without excessive nonhematologic regimen related toxicity. PMID- 20351644 TI - Spectrum of inherited bleeding disorders in southern Iran, before and after the establishment of comprehensive coagulation laboratory. PMID- 20351645 TI - Carbon monoxide releasing molecule-2 enhances coagulation in rat and rabbit plasma. PMID- 20351650 TI - A comparison of the performance of the EQ-5D and the EQ-5D-Y health-related quality of life instruments in South African children. AB - The aim of this study was to investigate the performance of the recent EQ-5D-Y instrument compared with the standard EQ-5D in assessing the health-related quality of life of high school children in Cape Town. Either the EQ-5D or the EQ 5D-Y was given to high school children. The sample consisted of 521 respondents. The EQ-5D-Y was found to be superior in that there were statistically significant fewer missed item responses, both in the domains and the health status Visual Analogue Scale (VAS). A grade differential was noted with more missing responses in the lower grades, particularly with the EQ-5D. More children reported problems with the mobility, self-care and anxiety and depression domains when responding to the EQ-5D-Y. In addition, the mean VAS score was marginally greater using the EQ-5D-Y. The EQ-5D-Y performed better than the EQ-5D, particularly in the younger children, and should be used in early secondary school. The EQ-5D-Y generated a wider range of responses in both the domains and the VAS, and may be more responsive than the Adult version. The two seem to give different results and consequently should be considered two related but separate instruments. PMID- 20351651 TI - Diffusion tensor imaging in a human PET/MR hybrid system. AB - PURPOSE: The aim of this study was to test and demonstrate the feasibility of diffusion tensor imaging (DTI) with a hybrid positron emission tomography (PET)/magnetic resonance imaging system for simultaneous PET and magnetic resonance (MR) data acquisition. MATERIALS AND METHODS: All measurements were performed with a prototype hybrid PET/MR scanner dedicated for brain and head imaging. The PET scanner, which is inserted into a conventional 3.0-Tesla high field MR imager equipped with a transmit/receive birdcage head coil, consists of 192 block detectors with a matrix of 12 x 12 lutetium oxyorthosilicate scintillation crystals combined with MR-compatible 3 x 3 avalanche photodiode arrays. In 7 volunteers and 4 patients with brain tumors, DTI was performed during simultaneous PET data readout applying a diffusion weighted echo planar sequence (12 noncollinear directions, echo time (TE)/repetition time (TR) 98 ms/5300 ms, b-value 800 s/mm). Image quality and accuracy of DTI were assessed in comparison with DTI images acquired after removal of the PET insert. RESULTS: The diffusion images showed good image quality in all volunteers regardless of simultaneous PET data readout or after removal of the PET scanner; however, significantly (P < 0.01) stronger rim artifacts were found in fractional anisotropy images computed from DTI images recorded during simultaneous PET acquisition, demonstrating higher eddy-current effects. In region of interest analysis, no notable differences were found in the computation of the direction of the principal eigenvector (P > 0.05) and fractional anisotropy values (P > 0.05). In the assessment of pathologies, in all 4 patients PET and DTI provided important clinical information in addition to conventional magnetic resonance imaging. CONCLUSION: Diffusion tensor imaging may be combined with simultaneous PET data acquisition, offering additional important morphologic and functional information for treatment planning in patients with brain tumors. PMID- 20351652 TI - Gadofosveset-enhanced magnetic resonance imaging of human carotid atherosclerotic plaques: a proof-of-concept study. AB - OBJECTIVE: To investigate the potential of gadofosveset-enhanced MR imaging for the characterization of human carotid atherosclerotic plaques. MATERIALS AND METHODS: Sixteen (9 symptomatic, 7 asymptomatic) patients with 70% to 99% carotid stenosis (according to NASCET criteria) were included (13 men, 3 women, mean age 67.6 years). All patients underwent baseline precontrast MR imaging of the carotid plaque. Immediately after completion of the baseline examination, 0.03 mmol/kg gadofosveset was administered. At 24 hours postinjection, the acquisition was repeated. Twelve patients were scheduled for carotid endarterectomy. Carotid endarterectomy specimens were HE-, CD31-, CD68-, and albumin-stained to correlate signal enhancement with plaque composition, intraplaque microvessel density, and macrophage and albumin content. A random intercept model was used to compare signal enhancement between symptomatic and asymptomatic patients, adjusting for size of various plaque components. This study was approved by the institutional medical ethics committee. All participants gave written informed consent. RESULTS: Signal enhancement (SE) of the plaque was significantly higher in symptomatic patients compared with asymptomatic patients (median log SE 0.182 vs. -0.109, respectively, P < 0.001). A positive association (as expressed by a regression coefficient beta = 0.0035) was found between signal enhancement on the log scale and intraplaque albumin content (P = 0.038). There was no association between signal enhancement and various other plaque components. CONCLUSION: In this study, the potential of gadofosveset-enhanced human carotid plaque MR imaging for identification of high-risk plaques was demonstrated. Signal enhancement of the plaque after administration of gadofosveset was associated with differences in intraplaque albumin content. Although promising, we emphasize that these results are based on a small patient population. Larger prospective studies are warranted. PMID- 20351653 TI - Intraindividual in vivo comparison of gadolinium contrast agents for pharmacokinetic analysis using dynamic contrast enhanced magnetic resonance imaging. AB - PURPOSE: To compare the intraindividual differences of dynamic signal characteristics for 3 gadolinium chelates (gadopentetate dimeglumine [Gd-DTPA], gadodiamide [Gd-DTPA-BMA], and gadobenate dimeglumine [Gd-BOPTA]) using dynamic contrast enhanced magnetic resonance (MR) imaging (DCE-MRI) with a preclinical beagle model at 7 Tesla. METHOD AND MATERIALS: Seven beagles were scanned 3 times each with a 7-day interval between the scans on a 7T whole body MRI system (Achieva, Philips) using a T/R head coil. Three different Gd contrast agents including Gd-DTPA, Gd-DTPABMA, and Gd-BOPTA were injected in a randomized order with a power injector (Spectris, MedRad, Indianola, PA) using dose of 0.1 mmol/kg body weight and flow rate of 0.06 mL/s. During image acquisition and data analysis, the identity of the specific contrast agent used for each examination was blinded. A 3D RF-spoiled fast field echo sequence was used for dynamic scans with in-plane spatial resolution 0.47 x 0.47 mm(2), temporal resolution of 9.5 seconds, and a total of 60 time points. Regions of interest were drawn within the carotid arteries and muscle tissue to determine semiquantitative parameters including maximum enhancement ratio, area under the signal enhancement curve over 90 seconds after contrast injection (AUC_90), time to maximum signal enhancement (T(max)), and washout_score. Additionally, quantitative pharmacokinetic parameters were measured in muscle tissues by applying 3 separate 2-compartment models; (1) artery input function (AIF) based Tofts model, (2) Brix model without AIF, and (3) AIF decomposed refined Brix model. RESULTS: Gd-BOPTA produced higher signal to noise ratio on postcontrast T1- weighted images than the other 2 Gd based contrast agents at 7T. Quantitatively, Gd-BOPTA provided a significantly higher maximum enhancement ratio (P < 0.01), AUC_90 (P < 0.01) and washout_score (P < 0.01) in beagle musculature and cranial vasculature compared with both Gd DTPA and Gd-DTPA-BMA. Among all the quantitative pharmacokinetic parameters, only the exchange rate constants (kep) calculated from these 3 models did not show a significant difference among the various contrast agents. CONCLUSIONS: Gd chelate containing MR contrast agents can be used at 7T for DCEMRI. Gd-BOPTA demonstrates stronger signal enhancement than standard Gd chelates, in concordance with the results of studies at lower fields. The observed enhancement characteristics for the 3 contrast agents demonstrate that the pharmacokinetic parameter kep is more robust in various models using DCE-MRI than the other pharmacokinetic parameters. This information is important relative to multisite clinical trials and long-term clinical studies that often use several different contrast agents and different models. PMID- 20351654 TI - Using standard nonenhanced axial scans for cerebral CT angiography bone elimination: feasibility study. AB - OBJECTIVE: To investigate the feasibility of using standard nonenhanced axial mode scans as precontrast scans for bone elimination in cerebral CT angiography (CTA). MATERIALS AND METHODS: A consecutive dataset of 32 patients who had both cerebral nonenhanced CT (NECT) (scanned in axial mode) and subtraction CTA (scanned in helical mode) examinations between April and August 2008 were retrospectively analyzed. For each patient, both axial- and helical-mode, NECT scans were processed by using the matched mask bone elimination (MMBE) method. Bone masks generated from axial- and helical-mode NECT scans were quantitatively compared by using overlapping analyses. The diagnostic quality and noise level of the resultant, maximum intensity projection, images by using 2 different bone masks were visually evaluated by 2 neuroradiologists independently using a 5 point scale (inferior, 1; worse, 2; equivalent, 3; better, 4; superior, 5). The effective doses to patients were estimated by using a dose-length product method. RESULTS: Of the 28 (87.5%) patients without intrascan movements, overlap rates between axial- and helical-mode bone masks ranged from 99.2% to 99.9% (mean, 99.7% +/- 0.2%). The mean diagnostic quality and noise level scores of resultant maximum intensity projection images given by 2 neuroradiologists were 3.0 +/- 0.3 and 2.5 +/- 0.5, respectively. The effective dose to patients with a routine brain CTA examination can be reduced from 1.16 to 0.78 mSv (16 cm, field-of-view) by using the proposed method if standard axial-mode NECT scans of the head are readily available. CONCLUSION: We found that using standard axial-mode NECT scans for bone elimination in helical-mode CTA is feasible. This method can further lower radiation dose without compromising the diagnostic quality. PMID- 20351656 TI - Body composition from birth to 4.5 months in infants born to non-obese women. AB - Infant body composition is affected by maternal obesity, which results in increased % body fat in the infant. With the rapidly increasing incidence of obesity, it is important that normative data are available for infant body composition that is not affected by this trend in maternal obesity. This study assessed body composition in infants born at term to women with a BMI between 18.5 and 25. Infant % body fat, fat mass (FM), and fat free mass (FFM) were assessed at birth, 6 wk, 3 mo, and 4.5 mo of age by air displacement plethysmography, using the PEA POD body composition system. The effects of age, gender, GA, and feeding mode on these parameters were assessed. The % body fat doubled between birth and 6 wk of age and then increased at a slower rate. FFM was higher in male infants at all ages, whereas % body fat was higher in female infants at 4.5 mo. There was a trend to increased % fat and decreased FFM in breastfed (BF) infants. The study provides unique data regarding changes in infant body composition and growth in infants born to women in the healthy weight range. PMID- 20351655 TI - Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain. AB - Little is known about roles of inflammation and hypoxic ischemia (HI) in the generation of neuroinflammation and damage of blood-brain barrier (BBB) in the white matter (WM) that displays regional vulnerability in preterm infants. We investigated whether low-dose lipopolysaccharide (LPS) sensitizes HI-induced WM injury in postpartum (P) day 2 rat pups by selectively increasing neuroinflammation and BBB damage in the WM. Pups received LPS (0.05 mg/kg) (LPS + HI) or normal saline (NS + HI) followed by 90-min HI. LPS and NS group were the pups that had LPS or NS only. Myelin basic protein immunohistochemistry on P11 showed WM injury in LPS + HI group, but not in NS + HI, LPS, and NS groups. In contrast, no gray matter injury was found in the four groups. LPS + HI group also showed decreased number of oligodendrocytes in the WM 72-h postinsult. In the same brain region, increases of activated microglia, TNF-alpha expression, BBB leakage, and cleaved caspase-3 positive cells were much more prominent in LPS + HI group than in the other three groups 24-h postinsult. The oligodendrocytes were the major cells with cleaved caspase-3 expression. We concluded that low dose LPS sensitized HI-induced WM injury in the immature brain by selectively up regulating neuroinflammation and BBB damage in the WM. PMID- 20351658 TI - Metabolomics of volatile organic compounds in cystic fibrosis patients and controls. AB - In cystic fibrosis (CF), airway inflammation causes an increased production of reactive oxygen species, responsible for degradation of cell membranes. During this process, volatile organic compounds (VOCs) are formed. Measurement of VOCs in exhaled breath of CF patients may be useful for the assessment of airway inflammation. This study investigates whether "metabolomics' of VOCs could discriminate between CF and controls, and between CF patients with and without Pseudomonas colonization. One hundred five children (48 with CF, 57 controls) were included in this study. After exhaled breath collection, samples were transferred onto tubes containing active carbon to adsorb and stabilize VOCs. Samples were analyzed by gas chromatography-time of flight-mass spectrometry to assess VOC profiles. Analysis showed that 1099 VOCs had a prevalence of at least 7%. By using 22 VOCs, a 100% correct identification of CF patients and controls was possible. With 10 VOCs, 92% of the subjects were correctly classified. The reproducibility of VOC measurements with a 1-h interval was very good (match factor 0.90 +/- 0.038). We conclude that metabolomics of VOCs in exhaled breath was possible in a reproducible way. This new technique was able to discriminate not only between CF patients and controls but also between CF patients with or without Pseudomonas colonization. PMID- 20351659 TI - Aquaporin-4 gene variation and sudden infant death syndrome. AB - The purpose of this study was to investigate the aquaporin-4 (AQP4) gene in cases of sudden infant death syndrome (SIDS) and controls and to elucidate the hypothesis that a genetically determined disturbed water homeostasis in the brain is involved as a predisposing factor in SIDS. The single nucleotide polymorphisms (SNPs) rs2075575, rs4800773, rs162004, and rs3763043 in the AQP4 gene were investigated in 141 SIDS cases and 179 controls. For each SIDS case, a brain/body weight ratio was calculated. The study revealed an association between the T allele and the CT/TT genotypes of rs2075575 and SIDS (C versus T, p < 0.01; CC versus CT/TT, p = 0.03). For the other three investigated SNPs, there were no differences in genotype frequencies between SIDS cases and controls. For the SNP rs2075575, it was also found an association between brain/body weight ratio and genotype in the SIDS cases aged 0.3-12 wk (p = 0.014, median ratio CC 10.6, CT/TT 12.1). In conclusion, this study indicates that rs2075575 may be of significance as a predisposing factor for SIDS, and that the CT/TT genotypes are associated with an increased brain/body weight ratio in infants dying from SIDS during the vulnerable period from birth up to 3 mo of age. PMID- 20351661 TI - Time to think out of the (ice) box. PMID- 20351657 TI - New approaches to neuroprotection in infant heart surgery. AB - Advances in surgical techniques and perioperative management have led to dramatic improvements in outcomes for children with complex congenital heart disease (CHD). As the number of survivors continues to grow, clinicians are becoming increasingly aware that adverse neurodevelopmental outcomes after surgical repair of CHD represent a significant cause of morbidity, with widespread neuropsychologic deficits in as many as 50% of these children by the time they reach school age. Modifications of intraoperative management have yet to measurably impact long-term neurologic outcomes. However, exciting advances in our understanding of the underlying mechanisms of cellular injury and of the events that mediate endogenous cellular protection have provided a variety of new potential targets for the assessment, prevention, and treatment of neurologic injury in patients with CHD. In this review, we will discuss the unique challenges to developing neuroprotective strategies in children with CHD and consider how multisystem approaches to neuroprotection, such as ischemic preconditioning, will be the focus of ongoing efforts to develop new diagnostic tools and therapies. Although significant challenges remain, tremendous opportunity exists for the development of diagnostic and therapeutic interventions that can serve to limit neurologic injury and ultimately improve outcomes for infants and children with CHD. PMID- 20351662 TI - Current world literature. PMID- 20351663 TI - Chronic cerebrospinal venous insufficiency. PMID- 20351664 TI - Integrating CCSVI and CNS autoimmunity in a disease model for MS. PMID- 20351665 TI - Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebro spinal venous insufficiency. AB - The truncular venous malformation (VM) represents an embryologically defective vein where developmental arrest has occurred during the vascular trunk formation period in the 'later stage' of the embryonic development. A relatively simple truncular VM lesion such as a venous web at the hepatic venous outlet causes portal hypertension giving a profound damage/impact to the liver. A similar condition involving the head and neck venous system may cause chronic cerebro spinal venous insufficiency (CCSVI) and may be involved in the development or exacerbation of multiple sclerosis. PMID- 20351666 TI - Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis. AB - AIM: The aim of this open-label study was to assess extracranial Doppler criteria of chronic cerebrospinal venous insufficiency in multiple sclerosis patients. METHODS: Seventy patients were assessed: 49 with relapsing-remitting, 5 with primary progressive and 16 with secondary progressive multiple sclerosis. The patients were aged 15-58 years and they suffered from multiple sclerosis for 0.5 40 years. Sonographic signs of abnormal venous outflow were detected in 64 patients (91.4%). RESULTS: We found at least two of four extracranial criteria in 63 patients (90.0%), confirming that multiple sclerosis is stronghly associated with chronic cerebrospinal venous insufficiency. Additional transcranial investigations may increase the rate of patients found positive in our survey. Reflux in internal jugular and/or vertebral veins was present in 31 cases (42.8%), stenosis of internal jugular veins in 61 cases (87.1%), not detectable flow in internal jugular and/or vertebral veins in 37 cases (52.9%) and negative difference in cross-sectional area of the internal jugular vein assessed in the supine vs. sitting position in 28 cases (40.0%). Flow abnormalities in the vertebral veins were found in 8 patients (11.4%). Pathologic structures (membranaceous or netlike septa, or inverted valves) in the junction of internal jugular vein with brachiocephalic vein were found in 41 patients (58.6%), in 15 patients (21.4%) on one side only and in 26 patients (37.1%) bilaterally. CONCLUSION: Multiple sclerosis is highly correlated with chronic cerebrospinal venous insufficiency. These abnormalities in the extracranial veins draining the central nervous system can exist in various combinations. The most common pathology in our patients was the presence of an inverted valve or another pathologic structure (like membranaceous or netlike septum) in the area of junction of the IJV with the brachiocephalic vein. PMID- 20351667 TI - Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. AB - AIM: The aim of this study is to compare the hemodynamics and the morphology of the internal jugular veins using colour-Doppler and B-mode sonongraphy in multiple sclerosis patients (MS) and in controls. METHODS: The internal jugular veins of 25 MS patients and 25 controls were examined using colour Doppler and B mode ultrasound in sitting and supine positions, recording the changes in hemodynamics and the presence or absence of morphological changes. The presence of at least two of the extracranial Zamboni criteria in the same individual was considered positive for evidence of chronic cerebrospinal venous insufficiency (CCSVI). RESULTS: According to the described criteria, 92% of the MS patients showed abnormal findings and 84% of them showed evidence of CCSVI, however; only 24% of controls showed abnormal findings, but none of them showed evidence of CCSVI (OR=7.25, 95% CI 2.92-18.01, P<0.0001). CONCLUSION: Hemodynamic abnormalities and morphological changes involving the internal jugular vein are strongly associated with MS. These findings can be demonstrated by a non invasive, cost effective Doppler ultrasound criteria. PMID- 20351668 TI - The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis. AB - AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome described in multiple sclerosis (MS) patients, characterized by stenosis of the main extracranial veins with hampered cerebral venous outflow. In the original description echo-colour Doppler demonstrated to be an ideal non invasive tool for screening CCSVI patients, but the reproducibility was not assessed. Aim of this study is to assess the variability coefficient between trained and in not trained echo-colour Doppler operators. METHODS: Thirty-six (36) subjects, matched for age and gender, were subset in 3 groups (group A, 12 healthy controls, HC; group B, 12 multiple sclerosis patients, MS; group C, 12 patients with other neurological disease, OND) underwent echo-colour Doppler screening for CCSVI according to an original protocol previously described. The inter observer variability rate was assessed by comparing respectively trained vs not trained operators, and trained vs trained operators, by using the same echo-colour Doppler equipment. In addition, by scanning 15 subjects after one month from the first session, intra observer coefficient was also assessed in trained operator. RESULTS: The inter observer variability rate between trained and not trained echo-colour Doppler operators, were not completely satisfactory (K coefficient 0.47 95% CI 0.27 0.68). To the contrary the inter observer agreement between trained operators was much more reliable (K coefficient 0.80 95% CI 0.59-1.01). Finally, the intra observer variability rate in trained operators was 0.93, (95% CI 0.80-1.06) confirming a highly satisfactory agreement. CONCLUSION: Echo-colour Doppler is a powerful, non-invasive and reproducible tool for screening CCSVI-MS but it needs special training. PMID- 20351669 TI - Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls. AB - AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of primary veins outside the skull that restrict normal outflow of blood from the brain. CCSVI was recently described as highly prevalent in patients with multiple sclerosis (MS), and can be non-invasively diagnosed by Doppler sonography (DS) and invasively by selective venography (SV). The aim of this paper was to investigate the value of neck magnetic resonance venography (MRV) for the diagnosis of CCSVI compared to DS and SV in patients with MS and in healthy controls (HC). METHODS: Ten MS patients and 7 HC underwent DS, 2D-Time-Of-Flight venography (TOF) and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). MS patients also underwent SV. The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS. SV has been considered the diagnostic gold standard for MS patients. RESULTS: All MS patients and none of the HC presented CCSVI, according to the DS criteria. This was confirmed by SV. For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, whereas the figures were 40%, 85%, 58%, 80% and 50% for 3D-TRICKS, and 30%, 85%, 52%, 75% and 46% for 2D-TOF in the IJVs. In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, 75%, 95%, 94% and 100%, whereas the figures were 31%, 100%, 45%, 100% and 26% for 3D-TRICKS and 25%, 100%, 40%, 100% and 25% for 2D-TOF in the IJVs. CONCLUSION: The use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV. PMID- 20351670 TI - CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study. AB - AIM: We previously reported unexpectedly robust associations between vascular haemodynamic (VH) anomalies in the principal extracranial cerebral veins, causing chronic cerebrospinal venous insufficiency (CCSVI), and multiple sclerosis (MS). Aim of this study was to investigate the relationship between the VH changes and MRI measures of MS disease severity in a cross sectional survey. METHODS: The number of anomalous VH criteria were measured using an echo-color Doppler, whereas CSF flow, atrophy and lesion measures were obtained from quantitative magnetic resonance imaging (MRI) analysis in sixteen consecutive relapsing remitting MS patients, (mean age: 36.1+/-SD 7.3 years, disease duration: 7.5+/ 1.9 years and median EDSS: 2.5) and in 8 healthy controls (HC) with similar age and sex distributions. RESULTS: All 16 MS patients investigated and none of the HCs met the VH criteria for CCSVI (P<0.0001). MS patients showed significantly lower net CSF flow compared to the HC (P=0.038) that was associated with number of anomalous VH criteria present (r=0.79, P<0.001). Moreover, increases in the number of anomalous VH criteria present were negatively associated with lower whole brain volume (Spearman R=-0.5, P=0.05). CONCLUSION: VH changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume. PMID- 20351671 TI - Iron stores and cerebral veins in MS studied by susceptibility weighted imaging. AB - AIM: In this paper, we seek to determine whether the iron deposition as seen by susceptibility weighted imaging (SWI) in the basal ganglia and thalamus of patients with multiple sclerosis is greater than the iron content measured in normal subjects (individuals unaffected by multiple sclerosis). As increased iron content may result from increased venous pressure, such information would add credence to the concept of Zamboni et al (1) that MS is caused by chronic cerebrospinal venous insufficiency. METHODS: Fourteen MS patients were recruited for this study with a mean age of 38 years ranging from 19 to 66 year-old. A velocity compensated 3D gradient echo sequence was used to generate SW images with a high sensitivity to iron content. We evaluated iron in the following structures: substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus and pulvinar thalamus. Each structure was broken into two parts, a high iron content region and a low iron content region. The measured values were compared to previously established baseline iron content in these structures as a function of age. RESULTS: Twelve of fourteen patients had an increase in iron above normal levels and with a particular pattern of iron deposition in the medial venous drainage system that was associated with the confluence of the veins draining that structure. CONCLUSION: Iron may serve as a biomarker of venous vascular damage in multiple sclerosis. The backward iron accumulation pattern seen in the basal ganglia and thalamus of most MS patients is consistent with the hypothesis of venous hypertension. PMID- 20351672 TI - Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility weighted imaging in patients with multiple sclerosis: a pilot case-control study. AB - AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. Aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes. METHODS: Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI. RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume. CONCLUSION: The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS. PMID- 20351673 TI - Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study. AB - AIM: Chronic fatigue (CF) severely affects patients with multiple sclerosis (MS), but its pathogenesis remains elusive and the effectiveness of available treatments is modest. We aimed to evaluate the effect on CF of the balloon dilatation of stenosing lesions affecting the main extracranial veins configuring the chronic cerebrospinal venous insufficiency (CCSVI), a condition strongly associated with MS. METHODS: Thirty-one MS consecutive patients (16 males, age 46.2+/-9.4 years) with associated CCSVI and CF underwent the endovascular procedure. Fatigue was assessed using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) at baseline (T0) and one (T1), six (T6) and twelve (T12) months after the procedure. In ambulatory patients (N.=28), mobility was evaluated using the 6-min walking test at T0 and T1. RESULTS: and MFIS scores significantly improved from preoperative values, and the positive trend was maintained at one year (FSS: T0=5.1+/-1.0 to T12=3.5+/-1.8, P<0.001; MFIS-total score: T0=34.9+/-14.8 to T12=22.5+/-13.7, P<0.001; MFIS-Physical subscale: T0=21.2+/-8.0 to T12=13.5+/-9.7 P<0.001; MFIS-Cognitive subscale: T0=9.2+/-9.5 to T12=6.0+/-6.3, P=0.03; MFIS-Psychosocial subscale: T0=4.5+/-2.1 to T12=2.5+/-2.1, P<0.001). Six-min walking distance (6MWD) at T1 improved significantly (332+/ 190m to 378+/-200m, P=0.0002). In addition, an inverted correlation between 6MWD and MFIS-physical subscale variations was found in the subgroup of patients (N.=8) with no lower limb motor impairment (r=-0.74, P=0.035). CONCLUSION: The reestablishment of cerebral venous return dramatically reduced CF perception in a group of MS patients with associated CCSVI, suggesting that CF is likely the symptom of CCSVI. PMID- 20351674 TI - Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course. AB - AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). CCSVI is detected by transcranial and extracranial color Doppler high-resolution examination (TCCS-ECD) and venography that permit to identify five types of venous malformations and four major (A-D) hemodynamic patterns of anomalous extracranial-extravertebral venous outflow. We investigated possible correlation between such hemodynamic patterns and both the symptoms at onset and clinical course in patients with MS and CCSVI. METHODS: TCCS-ECD, selective venography and clinical records of 65 patients affected by definite MS and CCSVI were reviewed. RESULTS: The four hemodynamic patterns of CCSVI were unevenly (P<0.0001) distributed with respect to the types of clinical presentation and course. In particular the Type A or B patterns were common in patients with onset of optic neuritis, but rare in patients presenting with spinal cord symptoms who typically showed a type D pattern. As well, the type A or type B hemodynamic were more common in patients with relapsing remitting course than in patients with secondary progressive course and rare in patients with primary progressive course. The C hemodynamic pattern was not observed in patients with primary progressive course who showed a remarkable prevalence of the type D pattern. CONCLUSION: The distribution of venous malformations and the resulting hemodynamic pattern show correlation with symptoms at onset and clinical course in patients with MS and CCSVI. PMID- 20351675 TI - Chronic cerebro-spinal venous insufficiency: report of transcranial magnetic stimulation follow-up study in a patient with multiple sclerosis. AB - The pyramidal pathway is frequently affected early on in multiple sclerosis (MS) and impaired motor performance is a major cause of disability. Pyramidal tract function can be assessed using transcranial magnetic stimulation (TMS). TMS supports the diagnosis of MS, detecting corticospinal tract involvement and monitoring its course with or without treatment. It has been never investigated whether any relationship exists between the TMS outcome measure and minimally invasive treatment of multiple severe extracranial stenosis, affecting the principal ce rebrospinal venous segments in MS patients. We report the clinical and transcranial magnetic stimulation follow-up of a patient during a relapse in relapsing-remitting MS. She underwent percutaneous balloon angioplasty of the associated chronic cerebrospinal venous insufficiency (CCSVI), due to membranous obstruction of the proximal azygous vein, with severe stenosis of the left internal jugular vein. Treatment of the associated CCSVI made a parallel improvement in both clinical and neurophysiological parameters, allowing us to avoid high dose steroid therapy. The relationship between the clinical and neurophysiological course on the one hand, and haemodynamic correction of the associated CCSVI on the other, calls for further exploration on a wider number of patients. The impact of CCSVI on the different neuro-physiological parameters has not been fully estimated, but the intriguing case here reported suggests that it may be greater than previously assumed. The demonstration of a modification of the cerebrovenous function with both clinical manifestation and via TMS suggests that the hampered cerebral venous return may contribute to the clinical course of MS. PMID- 20351676 TI - A consensus conference on complex biologics and low molecular weight heparins. PMID- 20351678 TI - Advances in hematology. Etiology and diagnosis of acquired von Willebrand syndrome. PMID- 20351679 TI - Advances in LLM. Ofatumumab: a new agent for chronic lymphocytic leukemia. PMID- 20351680 TI - Advances in drug development. BRAF validation in melanoma. PMID- 20351681 TI - Advances in oncology. Panitumumab and combination chemotherapy in first- and second-line therapy for colorectal cancer. PMID- 20351682 TI - Hypomethylating agent induction therapy followed by hematopoietic cell transplantation is feasible in patients with myelodysplastic syndromes. AB - Disease remission in patients with myelodysplastic syndromes can be achieved with azanucleosides, which act as pyrimidine analogs and hypomethylating agents. However, despite treatment with azanucleoside induction, patients with myelodysplastic syndromes nearly always relapse. Allogeneic hematopoietic cell transplantation (HCT) can be curative, but it is risky. Given that azanucleosides affect human leukocyte antigen expression and lymphocyte reactivity, we conducted a retrospective study to define the impact of pre-HCT azanucleoside therapy on post-HCT donor chimerism. Patients receiving azanucleoside induction therapy achieved rapid and high levels of donor chimerism post-transplant. Lineage analysis also found rapid donor chimerism of lymphocyte and granulocyte subsets. These data indicate the feasibility of pretransplant azanucleoside therapy in patients who subsequently receive an HCT. PMID- 20351683 TI - Rare AIDS-associated plasmablastic lymphoma as the initial presentation of AIDS. PMID- 20351684 TI - Plasmablastic lymphoma of the oral cavity type as the presenting manifestation of HIV infection. PMID- 20351685 TI - Heparin-induced thrombocytopenia in a patient treated with fondaparinux. PMID- 20351686 TI - Heparin-induced thrombocytopenia associated with fondaparinux. PMID- 20351687 TI - Measuring the 50% haemolytic complement (CH50) activity of serum. AB - The complement system is a group of proteins that when activated lead to target cell lysis and facilitates phagocytosis through opsonisation. Individual complement components can be quantified however this does not provide any information as to the activity of the pathway. The CH50 is a screening assay for the activation of the classical complement pathway (Fig 1) and it is sensitive to the reduction, absence and/or inactivity of any component of the pathway. The CH50 tests the functional capability of serum complement components of the classical pathway to lyse sheep red blood cells (SRBC) pre-coated with rabbit anti-sheep red blood cell antibody (haemolysin). When antibody-coated SRBC are incubated with test serum, the classical pathway of complement is activated and haemolysis results. If a complement component is absent, the CH50 level will be zero; if one or more components of the classical pathway are decreased, the CH50 will be decreased. A fixed volume of optimally sensitised SRBC is added to each serum dilution. After incubation, the mixture is centrifuged and the degree of haemolysis is quantified by measuring the absorbance of the haemoglobin released into the supernatant at 540 nm. The amount of complement activity is determined by examining the capacity of various dilutions of test serum to lyse antibody coated SRBC. This video outlines the experimental steps involved in analysing the level of complement activity of the classical complement pathway. PMID- 20351688 TI - Self-sufficient control of urate homeostasis in mice by a synthetic circuit. AB - Synthetic biology has shown that the metabolic behavior of mammalian cells can be altered by genetic devices such as epigenetic and hysteretic switches, timers and oscillators, biocomputers, hormone systems and heterologous metabolic shunts. To explore the potential of such devices for therapeutic strategies, we designed a synthetic mammalian circuit to maintain uric acid homeostasis in the bloodstream, disturbance of which is associated with tumor lysis syndrome and gout. This synthetic device consists of a modified Deinococcus radiodurans-derived protein that senses uric acids levels and triggers dose-dependent derepression of a secretion-engineered Aspergillus flavus urate oxidase that eliminates uric acid. In urate oxidase-deficient mice, which develop acute hyperuricemia, the synthetic circuit decreased blood urate concentration to stable sub-pathologic levels in a dose-dependent manner and reduced uric acid crystal deposits in the kidney. Synthetic gene-network devices providing self-sufficient control of pathologic metabolites represent molecular prostheses, which may foster advances in future gene- and cell-based therapies. PMID- 20351689 TI - High-resolution DNA analysis of human embryonic stem cell lines reveals culture induced copy number changes and loss of heterozygosity. AB - Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected. PMID- 20351690 TI - Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. AB - MicroRNAs (miRNAs) are increasingly implicated in the regulation of metastasis. Despite their potential as targets for anti-metastatic therapy, miRNAs have only been silenced in normal tissues of rodents and nonhuman primates. Therefore, the development of effective approaches for sequence-specific inhibition of miRNAs in tumors remains a scientific and clinical challenge. Here we show that systemic treatment of tumor-bearing mice with miR-10b antagomirs-a class of chemically modified anti-miRNA oligonucleotide-suppresses breast cancer metastasis. Both in vitro and in vivo, silencing of miR-10b with antagomirs significantly decreases miR-10b levels and increases the levels of a functionally important miR-10b target, Hoxd10. Administration of miR-10b antagomirs to mice bearing highly metastatic cells does not reduce primary mammary tumor growth but markedly suppresses formation of lung metastases in a sequence-specific manner. The miR 10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate for the development of new anti-metastasis agents. PMID- 20351691 TI - Derivation, propagation and controlled differentiation of human embryonic stem cells in suspension. AB - Undifferentiated human embryonic stem cells (hESCs) are currently propagated on a relatively small scale as monolayer colonies. Culture of hESCs as floating aggregates is widely used for induction of differentiation into embryoid bodies. Here we show that hESC lines can be derived from floating inner cell masses in suspension culture conditions that do not involve feeder cells or microcarriers. This culture system supports prolonged propagation of the pluripotent stem cells as floating clusters without their differentiation into embryoid bodies. HESCs cultivated as aggregates in suspension maintain the expression of pluripotency markers and can differentiate into progeny of the three germ layers both in vitro and in vivo. We further show the controlled differentiation of hESC clusters in suspension into neural spheres. These results pave the way for large-scale expansion and controlled differentiation of hESCs in suspension, which would be valuable in basic and applied research. PMID- 20351692 TI - The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. AB - Inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1beta (IL-1beta) and IL-18. AIM2 has been shown to bind DNA and engage the caspase-1-activating adaptor protein ASC to form a caspase-1 activating inflammasome. Using Aim2-deficient mice, we identify a central role for AIM2 in regulating caspase-1-dependent maturation of IL-1beta and IL-18, as well as pyroptosis, in response to synthetic double-stranded DNA. AIM2 was essential for inflammasome activation in response to Francisella tularensis, vaccinia virus and mouse cytomegalovirus and had a partial role in the sensing of Listeria monocytogenes. Moreover, production of IL-18 and natural killer cell dependent production of interferon-gamma, events critical in the early control of virus replication, were dependent on AIM2 during mouse cytomegalovirus infection in vivo. Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity. PMID- 20351693 TI - The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. AB - Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens. PMID- 20351695 TI - Molecular and clinical dissection of CD24 antibody specificity by a comprehensive comparative analysis. AB - CD24 is a small, highly glycosylated cell surface protein that is linked to the membrane through a glycosyl-phosphatidylinositol anchor. It is overexpressed in many human carcinomas and its expression is linked to bad prognosis. Lately, lack or low expression of CD24 was used to identify tumor stem cells resulting in conflicting data on the usefulness of this marker. In many immunohistochemical studies, the mAb SN3b was used but the epitope and specificity of this antibody have never been thoroughly investigated. In other studies based mainly on cytofluorographic analysis, the mAb ML-5 was applied. In this study, we compared the epitope of mAb SN3b to the CD24 mAbs SWA-11 and ML-5 that both bind to the core protein of CD24. Using tissue microarrays and affinity-purified CD24 glycoforms, we observed only a partial overlap of SN3b and SWA11 reactivity. The mAb SN3b recognizes sialic acid most likely on O-linked glycans that can occur independently of the CD24 protein backbone. The SN3b epitope was not related to common sialylated cancer-associated glycan structures. Both SN3b epitope positive or negative CD24 glycoforms supported the binding of P-selectin and Siglec-5. In breast cancer, the SN3b reactivity was associated with bad prognosis, whereas SWA11 was not. In renal cell cancer, the SN3b epitope was completely absent but SWA11 reactivity was a prognostic factor. Our results shed new light on the tumorbiological role of CD24 and resolve discrepancies in the literature related to the use of different CD24 mAbs. PMID- 20351696 TI - Fibroblast-derived HB-EGF promotes Cdx2 expression in esophageal squamous cells. AB - The molecular basis of attaining columnar phenotype in Barrett's esophagus is poorly understood. One hypothesis states that factors locally produced by cells of mesenchymal origin in chronic reflux esophagitis induce metaplastic transformation. This study was performed to elucidate the factors secreted from fibroblasts that cause columnar phenotype in adjacent squamous epithelium. Human fibroblast cells were exposed to acidified medium for 20 min, followed by medium neutralization for 2 h, and then total RNA was hybridized to Sentrix Human-6 Expression BeadChips. Furthermore, esophageal mucosal biopsy specimens from reflux esophagitis patients were examined for HB-EGF expression using immunohistochemistry. In addition, cells from the human esophageal squamous epithelial cell line HET1A were treated with recombinant HB-EGF, and changes in expressions of Cdx2 and columnar markers were analyzed. The gene expression profile revealed significant upregulation of a variety of growth factors and inflammatory chemokines in response to acid exposure. Among them, HB-EGF was upregulated more than 10-fold. Biopsy specimens from reflux esophagitis patients showed a strong expression of HB-EGF in fibroblast cells underlying the damaged epithelium. Furthermore, in vitro stimulation of HET1A cells with HB-EGF increased Cdx2 in dose-dependent manners. Functional analysis of human Cdx2 promoter also revealed its upregulation by HB-EGF stimulation, showing the role of potential responsive elements (AP-1 and NF-kappaB) for its transcriptional activation. Moreover, the columnar markers cytokeratin 7 and villin were also upregulated by HB-EGF stimulation. HB-EGF induces several genes characteristics of columnar phenotypes of esophageal squamous epithelium in a paracrine manner. PMID- 20351694 TI - TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. AB - Sensors of pathogens, such as Toll-like receptors (TLRs), detect microbes to activate transcriptional programs that orchestrate adaptive responses to specific insults. Here we report that TLR4 and TLR2 specifically activated the endoplasmic reticulum (ER) stress sensor kinase IRE1alpha and its downstream target, the transcription factor XBP1. Previously described ER-stress target genes of XBP1 were not induced by TLR signaling. Instead, TLR-activated XBP1 was required for optimal and sustained production of proinflammatory cytokines in macrophages. Consistent with that finding, activation of IRE1alpha by ER stress acted in synergy with TLR activation for cytokine production. Moreover, XBP1 deficiency resulted in a much greater bacterial burden in mice infected with the TLR2 activating human intracellular pathogen Francisella tularensis. Our findings identify an unsuspected critical function for XBP1 in mammalian host defenses. PMID- 20351697 TI - Slow food, fast food and the control of food intake. AB - This Perspective focuses on two elements of our food supply and eating environment that facilitate high energy intake: a high eating rate and distraction of attention from eating. These two elements are believed to undermine our body's capacity to regulate its energy intake at healthy levels because they impair the congruent association between sensory signals and metabolic consequences. The findings of a number of studies show that foods that can be eaten quickly lead to high food intake and low satiating effects-the reason being that these foods only provide brief periods of sensory exposure, which give the human body insufficient cues for satiation. Future research should focus on the underlying physiological, neurological and molecular mechanisms through which our current eating environment affects our control of food intake. PMID- 20351698 TI - Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. AB - Enteroviruses are believed to contribute to the pathogenesis of type 1 diabetes mellitus (T1DM). In this Review, the interplay between infection with enteroviruses, the immune system and host genes is discussed. Data from retrospective and prospective epidemiological studies strongly suggest the involvement of enteroviruses, such as coxsackievirus B, in the development of T1DM. Enteroviral RNA and/or proteins can be detected in tissues of patients with T1DM. Isolation of coxsackievirus B4 from the pancreas of patients with T1DM or the presence of enteroviral components in their islets strengthens the hypothesis of a relationship between the virus and the disease. Enteroviruses can play a part in the early phase of T1DM through the infection of beta cells and the activation of innate immunity and inflammation. In contrast with its antiviral role, virus-induced interferon alpha can be deleterious, acting as an initiator of the autoimmunity directed against beta cells. Enteroviruses, through persistent and/or successive infections, can interact with the adaptive immune system. Host genes, such as IFIH1, that influence susceptibility to T1DM are associated with antiviral activities. An increased activity of the IFIH1 protein may promote the development of T1DM. An improved knowledge of the pathogenic mechanisms of enterovirus infections should help to uncover preventive strategies for T1DM. PMID- 20351699 TI - The molecular pathology of cancer. AB - Rapid technical advances in DNA sequencing and genome-wide association studies are driving the discovery of the germline and somatic mutations that are present in different cancers. Mutations in genes involved in cellular signaling are common, and often shared by tumors that arise in distinct anatomical locations. Here we review the most important molecular changes in different cancers from the perspective of what should be analyzed on a routine basis in the clinic. The paradigms are EGFR mutations in adenocarcinoma of the lung that can be treated with gefitinib, KRAS mutations in colon cancer with respect to treatment with EGFR antibodies, and the use of gene-expression analysis for ER-positive, node negative breast cancer patients with respect to chemotherapy options. Several other examples in both solid and hematological cancers are also provided. We focus on how disease subtypes can influence therapy and discuss the implications of the impending molecular diagnostic revolution from the point of view of the patients, clinicians, and the diagnostic and pharmaceutical companies. This paradigm shift is occurring first in cancer patient management and is likely to promote the application of these technologies to other diseases. PMID- 20351701 TI - Renal recovery with lenalidomide in a patient with bortezomib-resistant multiple myeloma. AB - BACKGROUND: A 51-year-old man presented with an 8 month history of migratory pain and weakness. INVESTIGATIONS: Conventional X-ray, MRI, laboratory investigations including serum electropheresis and immunofixation, measurement of the glomerular filtration rate and levels of serum creatinine and lactate dehydrogenase, and 24 h urine analysis for proteinuria. DIAGNOSIS: Durie-Salmon stage IIIB multiple myeloma with IgG lambda gammopathy and renal impairment associated with urinary excretion of free lambda light chains. MANAGEMENT: Initially, the patient received supportive analgesia with metamizol and opioids, erythropoiesis stimulating agents and monthly administration of bisphosphonates. A standard regimen of bortezomib, doxorubicin and dexamethasone was started, but the patient did not respond and developed severe renal failure. Treatment was switched to low dose lenalidomide and high-dose dexamethasone. The lenalidomide dose was gradually increased up to 15 mg daily and the dexamethasone dose reduced to 40 mg once a week. Therapy was well tolerated, and the patient underwent autologous stem-cell transplantation around 16 months after start of induction treatment and 12 months after the start of lenalidomide-based therapy. At 2 years after initiation of lenalidomide-based therapy, the patient remains in partial remission with stable renal function and excellent performance status. PMID- 20351700 TI - Conscripts of the infinite armada: systemic cancer therapy using nanomaterials. AB - The field of clinical nanomaterials is enlarging steadily, with more than a billion US dollars of funding allocated to research by US government agencies in the past decade. The first generation of anti-cancer agents using novel nanomaterials has successfully entered widespread use. Newer nanomaterials are garnering increasing interest as potential multifunctional therapeutic agents; these drugs are conferred novel properties, by virtue of their size and shape. The new features of these agents could potentially allow increased cancer selectivity, changes in pharmacokinetics, amplification of cytotoxic effects, and simultaneous imaging capabilities. After attachment to cancer target reactive ligands, which interact with cell-surface antigens or receptors, these new constructs can deliver cytolytic and imaging payloads. The molecules also introduce new challenges for drug development. While nanoscale molecules are of a similar size to proteins, the paradigms for how cells, tissues and organs of the body react to the non-biological materials are not well understood, because most cellular and metabolic processes have evolved to deal with globular, enzyme degradable molecules. We discuss examples of different materials to illustrate interesting principles for development and future applications of these nanomaterial medicines with emphasis on the possible pharmacologic and safety hurdles for accomplishing therapeutic goals. PMID- 20351702 TI - Marfan syndrome. Part 2: treatment and management of patients. AB - Aortic disease is the main cause of death among patients with Marfan syndrome. Before the development of open surgery, most patients died in the fourth decade of life. Improvements in surgical techniques have facilitated prophylactic surgery and have dramatically changed the life expectancy of patients with Marfan syndrome. Valve-sparing techniques are becoming the standard surgical treatment for these patients, since the operative and long-term results are comparable with those obtained with the Bentall and De Bono procedure and their theoretical advantages over the Bentall and De Bono procedure are attractive for young patients. Distal aortic complications still cause substantial morbidity in patients who have undergone surgery. On the other hand, several medical approaches have appeared as alternatives or adjuncts to the standard treatment with beta-blockers. Mouse models of the disease have shown that the angiotensin II receptor blocker losartan can rescue the phenotype. Among female patients, pregnancy deserves special consideration. Aortic dissection occurs mainly in the third trimester of gestation and in patients with dilated aortas. As aortic dissection carries a high risk of maternal mortality and fetal demise, prophylactic aortic surgery is recommended before attempting pregnancy for those women with an aortic diameter exceeding 40 mm. PMID- 20351703 TI - Marfan syndrome. Part 1: pathophysiology and diagnosis. AB - Marfan syndrome is a connective-tissue disease inherited in an autosomal dominant manner and caused mainly by mutations in the gene FBN1. This gene encodes fibrillin-1, a glycoprotein that is the main constituent of the microfibrils of the extracellular matrix. Most mutations are unique and affect a single amino acid of the protein. Reduced or abnormal fibrillin-1 leads to tissue weakness, increased transforming growth factor beta signaling, loss of cell-matrix interactions, and, finally, to the different phenotypic manifestations of Marfan syndrome. Since the description of FBN1 as the gene affected in patients with this disorder, great advances have been made in the understanding of its pathogenesis. The development of several mouse models has also been crucial to our increased understanding of this disease, which is likely to change the treatment and the prognosis of patients in the coming years. Among the many different clinical manifestations of Marfan syndrome, cardiovascular involvement deserves special consideration, owing to its impact on prognosis. However, the diagnosis of patients with Marfan syndrome should be made according to Ghent criteria and requires a comprehensive clinical assessment of multiple organ systems. Genetic testing can be useful in the diagnosis of selected cases. PMID- 20351704 TI - Renal glucose transporters: novel targets for hyperglycemia management. AB - The naturally occurring substance phlorizin has long been recognized to block the reabsorption of glucose from the glomerular ultrafiltrate into the systemic circulation. The poor oral bioavailability and adverse effects associated with this agent, however, have prevented its use in clinical practice and restricted its use to that of a physiological tool. The development of novel agents that are able to block the principal glucose transporter in the kidney has allowed the inhibition of renal glucose reabsorption to be re-evaluated as a therapeutic tool in patients with diabetes mellitus. This Perspectives article summarizes current knowledge pertaining to glucose transport in the kidney and describes the evidence regarding glucose transport blockade as a novel target for the management of hyperglycemia in the context of existing treatment strategies. PMID- 20351707 TI - State of the journal-2010. PMID- 20351709 TI - Early and severe indirect hyperbilirubinemia as a manifestation of galactosemia. AB - Classic galactosemia results from mutations in the galactose-1-phosphate uridyl transferase gene and causes infants to present with jaundice after initiation of lactose containing formulas. Jaundice associated with galactosemia is often thought to have a prominent direct fraction. We report an infant with galactosemia who presented with severe jaundice from indirect hyperbilirubinemia and met criteria for an exchange transfusion within 48 h after milk ingestion. PMID- 20351708 TI - Prenatal closure of the ductus arteriosus and maternal ingestion of anthocyanins. AB - Prenatal closure of the ductus arteriosus (DA) is associated with maternal ingestion of cyclooxygenase inhibitors during pregnancy. We report a case of prenatal DA closure after maternal ingestion of MonaVie, a juice blend containing the cyclooxygenase and nitric oxide synthase inhibitors anthocyanins and proanthocyanidins. A G(2)P(0)Ab(1) woman had an uncomplicated first and second trimester and normal 20-week fetal ultrasound. At 37 weeks, she developed polyhydramnios; a fetal echocardiogram showed right atrial and ventricular (RV) enlargement with RV dysfunction. Immediately after birth, there was pulmonary hypertension by echocardiogram with DA closure, severe RV hypertrophy and dysfunction, and marked right-to-left atrial shunting. Improvement occurred over 3 weeks with the neonate tolerating room air and a follow-up echocardiogram showing minimal atrial shunting and improved RV function. This report shows an association between MonaVie ingestion throughout pregnancy and prenatal DA closure resulting in cardiac dysfunction and pulmonary hypertension at birth. PMID- 20351710 TI - Cantrell syndrome. PMID- 20351711 TI - Regional care model enables rapid response to adverse drug events. PMID- 20351705 TI - The role of endothelial function and its assessment in rheumatoid arthritis. AB - Patients with rheumatoid arthritis (RA) have a reduced life expectancy when compared with the general population, largely attributable to cardiovascular disease. Factors that contribute to this increased cardiovascular risk include traditional risk factors, which account for only part of the excess, along with manifestations of the disease itself. RA is characterized by inflammation, which also is a key component in the development of atherosclerosis. Inflammation leads to the activation of endothelial cells, which, through an increase in the expression of leukocyte adhesion molecules, promotes a pro-atherosclerotic environment. Endothelial dysfunction is an early preclinical marker of atherosclerosis, and is commonly found in patients with RA. Several methods are available for the assessment of endothelial function, such as flow-mediated dilatation and laser Doppler flowmetry combined with iontophoresis, each with its own advantages and limitations. Studies have shown that endothelial dysfunction in RA is closely associated with inflammation, and therapeutic reduction of inflammation leads to improvements in endothelial function. As such, assessments of endothelial function could prove to be useful tools in the identification and monitoring of cardiovascular risk in patients with RA. Given the increase in cardiovascular mortality associated with RA, effective management must involve prevention of cardiovascular risk, in addition to control of disease activity and inflammation. PMID- 20351712 TI - Re: Maternal consumption of polyphenol-rich foods in late pregnancy and fetal ductus arteriosus flow dynamics. PMID- 20351714 TI - Poor replication of candidate genes for major depressive disorder using genome wide association data. AB - Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case-control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P=0.038; odds ratio (OR) AT=1.10, 95% CI 0.95-1.29; OR TT=1.21, 95% confidence interval (CI) 1.01-1.47) and NPY (rs16139; P=0.034; OR C allele=0.73, 95% CI 0.55-0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13-1.63; P=0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P=0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors. PMID- 20351715 TI - Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. PMID- 20351716 TI - Convergence of linkage, association and GWAS findings for a candidate region for bipolar disorder and schizophrenia on chromosome 4p. PMID- 20351717 TI - A systemic toxicity index developed to assess peripheral changes in mood episodes. PMID- 20351718 TI - Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish? AB - While the research community has accepted the value of rodent models as informative research platforms, there is less awareness of the utility of other small vertebrate and invertebrate animal models. Neuroscience is increasingly turning to smaller, non-rodent models to understand mechanisms related to neuropsychiatric disorders. Although they can never replace clinical research, there is much to be learnt from 'small brains'. In particular, these species can offer flexible genetic 'tool kits' that can be used to explore the expression and function of candidate genes in different brain regions. Very small animals also offer efficiencies with respect to high-throughput screening programs. This review provides a concise overview of the utility of models based on worm, fruit fly, honeybee and zebrafish. Although these species may have small brains, they offer the neuropsychiatric research community opportunities to explore some of the most important research questions in our field. PMID- 20351720 TI - A risk marker for alcohol dependence on chromosome 2q35 is related to neuroticism in the general population. PMID- 20351721 TI - The CACNA1C risk variant for bipolar disorder influences limbic activity. PMID- 20351719 TI - Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder. AB - Genetic variation in the cholinergic muscarinic-2 (M(2)) receptor gene (CHRM2) has been associated with the risk for developing depression. We previously reported that M(2)-receptor distribution volume (V(T)) was reduced in depressed subjects with bipolar disorder (BD) relative to depressed subjects with major depressive disorder (MDD) and healthy controls (HCs). In this study, we investigated the effects of six single-nucleotide polymorphisms (SNPs) for CHRM2 on M(2)-receptor binding to test the hypotheses that genetic variation in CHRM2 influences M(2)-receptor binding and that a CHRM2 polymorphism underlies the deficits in M(2)-receptor V(T) observed in BD. The M(2)-receptor V(T) was measured using positron emission tomography and [(18)F]FP-TZTP in unmedicated, depressed subjects with BD (n=16) or MDD (n=24) and HCs (n=25), and the effect of genotype on V(T) was assessed. In the controls, one SNP (with identifier rs324650, in which the ancestral allele adenine (A) is replaced with one or two copies of thymine (T), showed a significant allelic effect on V(T) in the pregenual and subgenual anterior cingulate cortices in the direction AAor=40 years with a mean BMI of 29.6(+/- 6.6) kg m(-2). Pathological, clinical and demographic data were retrieved from electronic medical records. Multinomial logistic regression analysis was preformed to estimate the risk of more advanced stages and poorly differentiated grade of cancer, adjusting for covariates. RESULTS: Obese compared with normal weight women had an 80% increased risk of cancer with more advanced stages (III/IV) and poorly differentiated grade (odds ratio = 1.80, 95% confidence interval 1.13-2.86, P = 0.014). No significant increase in risk was observed for overweight women. CONCLUSION: Obesity at the time of diagnosis of breast cancer is associated with more advanced stages and poorly differentiated grade of cancers. PMID- 20351737 TI - No evidence of large differences in mother-daughter and father-son body mass index concordance in a large UK birth cohort. AB - It has recently been suggested that there are substantial differences in mother daughter and father-son associations of body mass index and obesity among contemporary UK children, but much larger studies of older cohorts have failed to find evidence of substantial sex-specific effects. We have tested this hypothesis using the Avon Longitudinal Study of Parents and Children, a large contemporary cohort. Our analyses are based on 4654 complete parent-offspring trios (2323 with male offspring and 2331 with female offspring, all aged approximately 7.5 years). We found maternal body mass index to be a little more strongly associated with female than with male offspring body mass index (beta=0.18 (95% confidence interval 0.16-0.20) for females vs 0.13 (0.12, 0.15) for males). However, associations between paternal body mass index and male compared with female offspring were very similar (beta=0.16 (0.14, 0.19) for females vs 0.15 (0.12, 0.17) for males). Hence, our study suggests that there is no compelling reason to integrate the belief that there are large differences in parent-offspring body mass index associations with obesity prevention strategies. PMID- 20351739 TI - Can Elvis Pretzley and the Fitwits improve knowledge of obesity, nutrition, exercise, and portions in fifth graders? AB - OBJECTIVE: To determine the effectiveness of an educational intervention, created with a human-centered design approach, on children's knowledge and beliefs related to obesity and nutrition. DESIGN: Pre-post intervention: we evaluated fifth graders (aged 9-12) from five urban schools using a survey instrument at 1 week before intervention, immediately after intervention, and 1 week later after intervention. SUBJECTS: Of 189 fifth graders enrolled in the schools, 165 consented students (87.3%) completed baseline data. We obtained immediate post intervention data from 94% of them and 1-week post-intervention data from 88%. RESULTS: Of the 14 instrument questions that covered items under obesity, disease, nutrition, portion sizes, and exercise, 11 showed significant improvements in the percentage of correct answers. The children's knowledge in specific areas, including the meaning of the term 'obesity' and portion sizes, increased dramatically. Participatory design, child-inspired characters, hand based portions, traditional games, and attention to reception by the students resulted in an engaging presentation. CONCLUSION: Simplified health vocabulary and multiple modes of presentation resulted in accessible and understandable health education regarding obesity, nutrition, exercise, and portion size. This study yields compelling evidence that the Fitwits tools are an effective method to promote knowledge about obesity. Future studies are needed to determine whether this knowledge can affect health outcomes. PMID- 20351740 TI - Placental FTO expression relates to fetal growth. AB - OBJECTIVE: The fat mass and obesity-associated gene (FTO) participates in the control of postnatal weight gain. We assessed whether FTO is expressed in human placenta and whether such expression relates to prenatal weight gain and to the rs9939609 single nucleotide polymorphism (SNP) in FTO. DESIGN AND SUBJECTS: In a birth cohort study, placentas from women (n = 147) with an uncomplicated, singleton, term pregnancy were weighed at delivery. Real-time PCR was used to study, in placental tissue, the expression of FTO and of housekeeping genes (TATA box binding protein and succinate dehydrogenase complex, subunit A) and to genotype the rs9939609 SNP in FTO. Weights and lengths of the newborns were measured; circulating insulin and insulin-like growth factor-I (IGF-I) were quantified in cord blood. RESULTS: FTO was highly expressed in placenta and was associated with increased fetal weight and length (P<0.001 to P<0.0001). Maternal parity showed an interaction (P<0.001) in the association between placental FTO expression and placental weight. Placental FTO mRNA expression was associated with increased fetal-to-placental weight ratio (P<0.005) in infants from primiparous women, and was associated with increased fetal weight and length and placental weight (P<0.001 to P<0.0001) in infants from nonprimiparous women. These associations were not explained by either cord insulin or IGF-I. Placental FTO expression was unrelated to placental FTO rs9939609 SNP. CONCLUSION: FTO is expressed in the human placenta. In a maternal parity-dependent manner, placental FTO may participate either in the control of fetal weight gain or in the partitioning between placental and fetal growth. PMID- 20351741 TI - Effect of weight loss by a low-fat diet and a low-carbohydrate diet on peptide YY levels. AB - OBJECTIVE: To compare the effects of weight loss by an energy-restricted low-fat diet vs low-carbohydrate diet on serum peptide YY (PYY) levels. DESIGN: 8-Week prospective study of 30 obese adults (mean age: 42.8+/-2.0 years, mean body mass index 35.5+/-0.6 kg m(-2)). RESULTS: After 8 weeks, subjects on the low carbohydrate diet lost substantially more weight than those on the low-fat diet (5.8 vs 0.99 kg, P<0.001). Weight loss by either diet resulted in a 9% reduction in both mean fasting serum PYY levels (baseline: 103.5+/-8.8 pg ml(-1), after weight loss: 94.1+/-6.5 pg ml(-1), P<0.01) and postprandial area under the curve (AUC) PYY (baseline: (20.5+/-1.5) x 10(3) pg h(-1) ml(-1), after weight loss: mean AUC PYY (18.8+/-1.4) x 10(3) pg h(-1) ml(-1), P<0.001). There was a trend towards lower levels of PYY with greater degrees of weight loss. CONCLUSIONS: Reduced PYY levels after weight loss by an energy-restricted low-fat or low carbohydrate diet likely represents a compensatory response to maintain energy homeostasis and contributes to difficulty in weight loss during energy-restricted diets. PMID- 20351742 TI - The IL-23/IL-17 axis may be important in obesity-associated cancer by way of the activation of multiple signal pathways. PMID- 20351743 TI - Superior mesenteric artery syndrome in a tetraplegic patient, 11 years after a spinal cord injury: a case report. AB - STUDY DESIGN: Case report. OBJECTIVE: To report on the need to consider the possibility of the superior mesenteric artery syndrome (SMAS) even after a long time from the initial spinal cord injury. SETTING: Ulsan, South Korea. METHODS: A 41-year-old man with complete tetraplegia was evaluated for nausea and vomiting. He had a cervical cord injury 11 years previously and his body mass index was 18.6 on admission. The contrast-enhanced abdominal computed tomography (CT) showed intestinal obstruction at the third-portion of the duodenum. With frequent position change and intravenous electrolyte support, the symptoms resolved. There was no relapse of the symptoms with some lifestyle modifications. CONCLUSION: Patients with spinal cord injury may develop SMAS even long after their initial injury. PMID- 20351744 TI - Editorial note on: Impaired immune response to voluntary arm crank ergometer exercise in patients with spinal cord injury. PMID- 20351745 TI - Evaluation of the influence of different types of seats on postural control in individuals with paraplegia. AB - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To assess the importance of proprioceptive and vision information on different types of wheelchair seats with regard to postural control in paraplegic individuals during static posture. SETTING: Centre of Rehabilitation at the University Hospital/FMRP-USP and Rehabilitation Outpatient Clinic at University Hospital/UNICAMP, Brazil. METHODS: This study involved 11 individuals with paraplegia. All individuals were submitted to an evaluation of static balance with their eyes open and closed in three different types of seats: wheelchair seat, foam seat and gel seat. Balance evaluation was performed by using the Polhemus system, in which body displacements and anteroposterior and mediolateral speeds were assessed in a static seated position in the different types of seats. Data were analyzed using analysis of variance. The differences were considered at P<0.05. RESULTS: No statistical differences were found between the three types of seats in terms of displacements and anteroposterior and mediolateral speeds, or between seats with individuals keeping their eyes open or closed (P>0.05). However, it was observed that body displacements were more prominent toward an anteroposterior than a mediolateral direction. CONCLUSION: This study suggests that individuals with paraplegia tend to exhibit a more anteroposterior body displacement than a mediolateral one, with no significant differences between the types of seats in both situations of eyes open and closed. PMID- 20351747 TI - Langerhans cells: critical regulators of skin immunity? AB - Langerhans cells (LC) are members of the heterogenous family of professional antigen presenting dendritic cells (DC). They are identified by the C-type lectin receptor Langerin and form a contiguous network in the epidermis. Consequently, LC are an integral part of the skin barrier to the environment and were considered to be critical inducers of skin immunity, whereas dermal DC were largely overlooked. However, with the identification of a distinct subset of Langerin expressing dermal DC, the situation in the skin has become more complex and the relative contribution of the different cutaneous DC populations in balancing immunity and tolerance has become a matter of active debate. Here, we briefly review the classical paradigm and recent challenges of LC function, before focusing on advances concerning their role in contact hypersensitivity and ultraviolet radiation-induced immunosuppression obtained with in vivo LC ablation models. We then discuss novel LC/DC-specific gene targeting approaches currently used to dissect the role of the regulatory cytokines transforming growth factor beta and interleukin-10 to govern LC and DC function in vivo. This second generation of LC-specific genetically engineered mice will considerably extend our understanding of the molecular control of LC function in regulating skin immunity and tolerance in the near future. PMID- 20351748 TI - Association of the 19S proteasomal ATPases with the ATPase-binding domain of CIITA is essential for CIITA stability and MHC class II expression. AB - Major histocompatibility class II (MHC class II) molecules are glycoproteins that present extracellular antigens to CD4(+) T cells and are essential for initiation of adaptive immune responses. MHC class II expression requires recruitment of a master regulator, the class II transactivator (CIITA), to the MHC class II promoter. Others and we have earlier linked CIITA to the ubiquitin-proteasome system by showing that mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation. We have further shown that the 26S proteasome also has non-proteolytic functions in MHC class II transcription, as 19S ATPase subunits of the 26S proteasome positively regulate MHC class II transcription and are necessary for stable promoter binding of CIITA. Although these basic requirements of the proteasome to initiate MHC class II transcription are known, how CIITA is recruited, stabilized, and degraded remains unclear. Here, we identify a novel N-terminal 19S ATPase-binding domain of CIITA. The ATPase-binding domain lies within the proline/serine/threonine-rich region of CIITA and encompasses a majority of the CIITA degron sequence. Absence of the ATPase-binding domain increases the half-life of CIITA, but blocks MHC class II surface expression, indicating that CIITA requires interaction with the 19S ATPases for both appropriate deployment and destruction. PMID- 20351746 TI - Langerhans cells as targets for immunotherapy against skin cancer. AB - Cancer is the second most common cause of death in the world. Treatment of cancer is very challenging and immunotherapy has been developed as a potential way to fight cancer. The main obstacle with immunotherapy is that cancer cells evolve from healthy body cells in response to an accumulation of genetic mutations. As a consequence, the immune system struggles to detect the abnormal cells as they are mainly recognized as self. This implies that equipping the immune system to eliminate cancer cells is tricky, yet represents a very efficient way to constrain the growth of tumors. We became interested in developing immunotherapeutical strategies against skin cancer in the context of our observations that Langerhans cells (LC) are very potent antigen presenting cells and are able to incorporate protein antigens and present them to CD4(+) and CD8(+) T cells in the skin-draining lymph nodes. As a consequence, we developed an immunization strategy through the skin, termed epicutaneous immunization. Protein antigen applied onto barrier-disrupted skin induces long-lasting cytotoxic T-cell responses, potent enough to control and inhibit tumor growth. In this review, we suggest that immunization strategies through the skin could be a promising new approach for the treatment of skin cancer. PMID- 20351749 TI - Atopic dermatitis: the role of Langerhans cells in disease pathogenesis. AB - The manifestation of atopic dermatitis (AD) results from a complex interaction of environmental factors, skin barrier defects and immunological phenomena. The initial events in AD remain unclear while much progress has been made in identifying the mechanisms leading to the manifestation and maintenance of allergic inflammation. AD pathogenesis can be approached from many different points of view. In this review, we describe findings in mouse models and in humans separately. We focus on recent findings that underscore the importance of Langerhans cells in initial mechanisms of skin inflammation in AD. PMID- 20351750 TI - Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. AB - Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19(*)2 (or 681 G > A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the (*)2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19(*)2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14-3.37); P = 0.02). When studies evaluating stent thrombosis (n = 4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23-6.54); P = 0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19(*)2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis. PMID- 20351751 TI - Impact of ABCC2 haplotypes on transcriptional and posttranscriptional gene regulation and function. AB - ABCC2 (MRP2) is an important export pump, expressed at tissue barriers. The genetic variants -24C>T, 1249G>A and 3972C>T are leading to inter-individual differences of bioavailability of various endogenous and exogenous compounds. Considering ABCC2 haplotypes, we investigated DNA-protein binding properties, mRNA secondary structure, mRNA stability, protein expression and transport activity in various cell lines and analyzed the bioavailability of talinolol in 24 healthy Caucasian volunteers; -24C>T had no clear influence on DNA-protein binding and the mRNA stability did not differ significantly. In transfected HEK293T/17 cells, haplotypes H9 (CGT), H10 (TGC) and H12 (TGT) had significantly lower protein expression, whereas H2 (CAC) exhibited significantly increased protein expression compared to the wild type (H1, CGC): 32.7 +/- 8.8, 73.1 +/- 6.3; 44.0 +/- 15.5 and 115.2 +/- 8.2%, respectively. This corresponded with efflux rates of the fluorescent dye glutathione-methylfluorescein in vitro and by trend with talinolol bioavailability in vivo. In conclusion our results show a haplotype-dependent influence on transport capacity of ABCC2, which seems to be mainly based on posttranscriptional modification of protein expression rather than transport rates. PMID- 20351752 TI - A polymorphism of the GTP-cyclohydrolase I feedback regulator gene alters transcriptional activity and may affect response to SSRI antidepressants. AB - Tetrahydrobiopterin (BH(4)) is an essential cofactor for synthesis of many neurotransmitters including serotonin. In serotonergic neurons, BH(4) is tightly regulated by GTP-cyclohydrolase I feedback regulator (GFRP). Given the pivotal role of the serotonergic system in mood disorders and selective serotonin reuptake inhibitors (SSRIs) antidepressant function, we tested the hypothesis that GFRP gene (GCHFR) variants would modify response to antidepressants in subjects with major depression. Two single nucleotide polymorphisms (rs7164342 and rs7163862) in the GCHFR promoter were identified and occurred as two haplotypes (GA or TT). A multiple regression analysis revealed that homozygous individuals for the TT haplotype were less likely to respond to the SSRI fluoxetine than to the tricyclic antidepressant nortriptyline (P = 0.037). Moreover, the TT haplotype showed a reduced transcription rate in luciferase reporter gene assays, which may impact on BH(4)-mediated neurotransmitter production, thus suggesting a biological process through which GCHFR promoter variants might influence antidepressant response. PMID- 20351754 TI - Einstein's grandchildren. PMID- 20351753 TI - A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion. AB - SLC30A8 encodes the beta-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT 8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM. PMID- 20351755 TI - Speaking truth to power? PMID- 20351756 TI - Of guerillas and cafes. PMID- 20351757 TI - Can bacteria save the planet? PMID- 20351758 TI - Prostate biopsy in Western Australia 1998-2004. AB - We reviewed the status of prostate cancer diagnosis in Western Australia (WA) with the aim of improving decision-making about PSA testing and prostate biopsy. Our patient cohort was 5145 men undergoing an initial biopsy for prostate cancer diagnosis in WA between 1998 and 2004. Transrectal ultrasound-guided biopsies were performed by one of 18 clinicians whereas all pathology was assessed by one urological pathologist. Cancer detection rates were 59% for initial biopsies and 32% for repeat biopsies. High-grade cancer (Gleason sum > or =7) accounted for 69 and 38% of tumours diagnosed on initial and repeat biopsy, respectively. The rates of cancer diagnosis and detection of high-grade tumours were both 1.6-fold higher in WA patients compared with those obtained at baseline screening of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial of US men (P<0.001). These higher than expected rates of cancer detection and high histological grade indicate that urological practice in WA between 1998 and 2004 was significantly more conservative than US practice over this time period, probably leading to underdiagnosis of prostate cancer. Our findings may be relevant to other countries where urological practice differs from that in the United States. PMID- 20351760 TI - Genotypic Diversity of Streptococcus mutans in Caries-Free and Caries-Active Preschool Children. AB - Aim. The aim of the present paper was to evaluate the genotypic diversity of S. mutans in caries-free and caries-active preschool children in Brazil. Design. Twenty-eight preschool children were examined regarding caries experience by the dmft index. DNA from 280 isolates of S. mutans was extracted. S. mutans evaluated using to the PCR method, with primers for the glucosyltransferase gene. The genetic diversity of S. mutans isolates was analyzed by arbitrary primed-PCR (AP PCR) reactions. The differences between the diversity genotypic and dmft/caries experience were evaluated by chi2 test and Spearman's correlation. Results. The Spearman correlation test showed a strong association between genotypic diversity and caries experience (r = 0.72; P < .001). There were more S. mutans genotypes in the group of preschool children with dental caries, compared with the caries free group. Among the children with more than 1 genotype, 13 had dental caries (2 to 5 genotypes) and 4 were caries-free (only 2 genotypes). Conclusion. Our results support the previous findings of genetic diversity of S. mutans in preschool children being associated with dental caries. The investigation of such populations may be important for directing the development of programs for caries prevention worldwide. PMID- 20351761 TI - Spatial effects, sampling errors, and task specialization in the honey bee. AB - Task allocation patterns should depend on the spatial distribution of work within the nest, variation in task demand, and the movement patterns of workers, however, relatively little research has focused on these topics. This study uses a spatially explicit agent based model to determine whether such factors alone can generate biases in task performance at the individual level in the honey bees, Apis mellifera. Specialization (bias in task performance) is shown to result from strong sampling error due to localized task demand, relatively slow moving workers relative to nest size, and strong spatial variation in task demand. To date, specialization has been primarily interpreted with the response threshold concept, which is focused on intrinsic (typically genotypic) differences between workers. Response threshold variation and sampling error due to spatial effects are not mutually exclusive, however, and this study suggests that both contribute to patterns of task bias at the individual level. While spatial effects are strong enough to explain some documented cases of specialization; they are relatively short term and not explanatory for long term cases of specialization. In general, this study suggests that the spatial layout of tasks and fluctuations in their demand must be explicitly controlled for in studies focused on identifying genotypic specialists. PMID- 20351759 TI - Occult and obscure gastrointestinal bleeding: causes and clinical management. AB - Occult gastrointestinal bleeding, defined as bleeding that is unknown to the patient, is the most common form of gastrointestinal bleeding and can be caused by virtually any lesion in the gastrointestinal tract. Patients with occult gastrointestinal bleeding include those with fecal occult blood and iron deficiency anemia (IDA). In men and postmenopausal women, IDA should be considered to be the result of gastrointestinal bleeding until proven otherwise. Indeed, the possibility of gastrointestinal tract malignancy in these patients means that gastrointestinal evaluation is nearly always indicated. Obscure gastrointestinal bleeding is defined as obvious bleeding from a difficult to identify source and is always recurrent. This form of bleeding accounts for approximately 5% of all cases of clinically evident gastrointestinal bleeding and is most commonly caused by bleeding from the small intestine. Capsule endoscopy and deep enteroscopy have had a major impact on the way that patients with occult and, in particular, obscure bleeding are managed. In this Review the causes, diagnostic evaluation and treatment of occult and obscure gastrointestinal bleeding are discussed. PMID- 20351762 TI - Boldness by habituation and social interactions: a model. AB - Most studies of animal personality attribute personality to genetic traits. But a recent study by Magnhagen and Staffan (Behav Ecol Sociobiol 57:295-303, 2005) on young perch in small groups showed that boldness, a central personality trait, is also shaped by social interactions and by previous experience. The authors measured boldness by recording the duration that an individual spent near a predator and the speed with which it fed there. They found that duration near the predator increased over time and was higher the higher the average boldness of other group members. In addition, the feeding rate of shy individuals was reduced if other members of the same group were bold. The authors supposed that these behavioral dynamics were caused by genetic differences, social interactions, and habituation to the predator. However, they did not quantify exactly how this could happen. In the present study, we therefore use an agent-based model to investigate whether these three factors may explain the empirical findings. We choose an agent-based model because this type of model is especially suited to study the relation between behavior at an individual level and behavioral dynamics at a group level. In our model, individuals were either hiding in vegetation or feeding near a predator, whereby their behavior was affected by habituation and by two social mechanisms: social facilitation to approach the predator and competition over food. We show that even if we start the model with identical individuals, these three mechanisms were sufficient to reproduce the behavioral dynamics of the empirical study, including the consistent differences among individuals. Moreover, if we start the model with individuals that already differ in boldness, the behavioral dynamics produced remained the same. Our results indicate the importance of previous experience and social interactions when studying animal personality empirically. PMID- 20351763 TI - Detection of viable but non cultivable Escherichia coli after UV irradiation using a lytic Qbeta phage. AB - In order to qualify the germicidal efficacy of ultraviolet (UV) disinfection system, we generally determine the reduction of viable bacteria after UV-C irradiation. However, the simple count of viable and cultivable bacteria in usual media cannot reflect whether or not the UV dose applied to disinfect water is sufficient to inactivate bacteria. Indeed, there is a bacterial mix in the UV treated water: dead bacteria, viable and cultivable bacteria and viable but noncultivable bacteria (VBNC). The third type of bacteria can constitute a potential risk for public health. In fact, VBNC bacteria can be active and cause diseases. Consequently, the combination of a conventional method used to measure colony-forming ability after UV disinfection and the determination of adsorption constants of a lytic Qbeta phage in relation to irradiated host cells by an increased UV dose (Escherichia coli ATCC 13965) allows the detection of active bacteria, which lose their cultivability in usual growth media, but keep the phage susceptibility. PMID- 20351764 TI - Learning Abilities and Disabilities: Generalist Genes, Specialist Environments. AB - Twin studies comparing identical and fraternal twins consistently show substantial genetic influence on individual differences in learning abilities such as reading and mathematics, as well as in other cognitive abilities such as spatial ability and memory. Multivariate genetic research has shown that the same set of genes is largely responsible for genetic influence on these diverse cognitive areas. We call these "generalist genes." What differentiates these abilities is largely the environment, especially nonshared environments that make children growing up in the same family different from one another. These multivariate genetic findings of generalist genes and specialist environments have far-reaching implications for diagnosis and treatment of learning disabilities and for understanding the brain mechanisms that mediate these effects. PMID- 20351765 TI - The Post-Communist Fertility Puzzle. AB - Fertility has unanimously declined across the entire post-communist region. This study explores the variation in fertility trends over time among these countries and assesses to what degree three explanations are applicable: second demographic transition (SDT), postponement transition (PPT) or reaction to the economic crisis. Moreover, on the basis of SDT and PPT theoretical tenets, as well as descriptive evidence, the economic context is hypothesized to be linked to two processes of fertility decline conversely. The results show that no one theoretical explanation is sufficient to explain the complex fertility declines across the entire post-communist region from 1990 to 2003. In some countries, a great part of the decline in fertility occurred before significant postponement of childbearing began, which indicates that the dramatic decline was due to stopping behavior or postponement of higher order births. Postponement of first births, either through PPT or SDT processes, greatly contributed to fertility decline in a small number of countries. Pooled cross-sectional time-series analyses of age-specific birthrates confirm that these two distinct processes are present and show that the economic crisis explanation has explanatory power for declining birth rates. In contrast, logistic regressions show that the likelihood of postponing childbirth increases with improved economic conditions. These results confirm the importance of taking the economic context into account when discussing explanations for fertility decline. More specifically, the results indicate that the severity and duration of economic crisis, or absence thereof, influenced the extent and manner in which fertility declined. PMID- 20351766 TI - A Simple & Convenient Solid Phase Synthesis of Bacterial Origin Octapeptide Sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH. AB - The repeating octapeptide sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH derived from the glycoprotein found in Staphylococcus aureus cell wall is assembled by simple solid phase peptide synthesis methodology using a base labile linker. PMID- 20351767 TI - Inflammation, thrombosis and vascular biology: translating ideas into cardiovascular research and therapy. PMID- 20351768 TI - Reinforcing reinforcement. PMID- 20351769 TI - Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. AB - Lantibiotic synthetases are remarkable biocatalysts generating conformationally constrained peptides with a variety of biological activities by repeatedly utilizing two simple posttranslational modification reactions: dehydration of Ser/Thr residues and intramolecular addition of Cys thiols to the resulting dehydro amino acids. Since previously reported lantibiotic synthetases show no apparent homology with any other known protein families, the molecular mechanisms and evolutionary origin of these enzymes are unknown. In this study, we present a novel class of lanthionine synthetases, termed LanL, that consist of three distinct catalytic domains and demonstrate in vitro enzyme activity of a family member from Streptomyces venezuelae. Analysis of individually expressed and purified domains shows that LanL enzymes install dehydroamino acids via phosphorylation of Ser/Thr residues by a protein kinase domain and subsequent elimination of the phosphate by a phosphoSer/Thr lyase domain. The latter has sequence homology with the phosphothreonine lyases found in various pathogenic bacteria that inactivate host mitogen activated protein kinases. A LanC-like cyclase domain then catalyzes the addition of Cys residues to the dehydro amino acids to form the characteristic thioether rings. We propose that LanL enzymes have evolved from stand-alone protein Ser/Thr kinases, phosphoSer/Thr lyases, and enzymes catalyzing thiol alkylation. We also demonstrate that the genes for all three pathways to lanthionine-containing peptides are widespread in Nature. Given the remarkable efficiency of formation of lanthionine-containing polycyclic peptides and the latter's high degree of specificity for their cognate cellular targets, it is perhaps not surprising that (at least) three distinct families of polypeptide sequences have evolved to access this structurally and functionally diverse class of compounds. PMID- 20351770 TI - Variable transcription factor binding: a mechanism of evolutionary change. AB - This primer discusses a study from Bradley et al. in which changes in transcription factor binding between two Drosophila species are revealed by chromatin immunoprecipitation and high-throughput sequencing. PMID- 20351771 TI - Reinforcement of gametic isolation in Drosophila. AB - Reinforcement, a process by which natural selection increases reproductive isolation between populations, has been suggested to be an important force in the formation of new species. However, all existing cases of reinforcement involve an increase in mate discrimination between species. Here, I report the first case of reinforcement of postmating prezygotic isolation (i.e., barriers that act after mating but before fertilization) in animals. On the slopes of the African island of Sao Tome, Drosophila yakuba and its endemic sister species D. santomea hybridize within a well-demarcated hybrid zone. I find that D. yakuba females from within this zone, but not from outside it, show an increase in gametic isolation from males of D. santomea, an apparent result of natural selection acting to reduce maladaptive hybridization between species. To determine whether such a barrier could evolve under laboratory conditions, I exposed D. yakuba lines derived from allopatric populations to experimental sympatry with D. santomea, and found that both behavioral and gametic isolation become stronger after only four generations. Reinforcement thus appears to be the best explanation for the heightened gametic isolation seen in sympatry. This appears to be the first example in animals in which natural selection has promoted the evolution of stronger interspecific genetic barriers that act after mating but before fertilization. This suggests that many other genetic barriers between species have been increased by natural selection but have been overlooked because they are difficult to study. PMID- 20351772 TI - The promise of prevention: the effects of four preventable risk factors on national life expectancy and life expectancy disparities by race and county in the United States. AB - BACKGROUND: There has been substantial research on psychosocial and health care determinants of health disparities in the United States (US) but less on the role of modifiable risk factors. We estimated the effects of smoking, high blood pressure, elevated blood glucose, and adiposity on national life expectancy and on disparities in life expectancy and disease-specific mortality among eight subgroups of the US population (the "Eight Americas") defined on the basis of race and the location and socioeconomic characteristics of county of residence, in 2005. METHODS AND FINDINGS: We combined data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to estimate unbiased risk factor levels for the Eight Americas. We used data from the National Center for Health Statistics to estimate age-sex-disease-specific number of deaths in 2005. We used systematic reviews and meta-analyses of epidemiologic studies to obtain risk factor effect sizes for disease-specific mortality. We used epidemiologic methods for multiple risk factors to estimate the effects of current exposure to these risk factors on death rates, and life table methods to estimate effects on life expectancy. Asians had the lowest mean body mass index, fasting plasma glucose, and smoking; whites had the lowest systolic blood pressure (SBP). SBP was highest in blacks, especially in the rural South--5-7 mmHg higher than whites. The other three risk factors were highest in Western Native Americans, Southern low-income rural blacks, and/or low-income whites in Appalachia and the Mississippi Valley. Nationally, these four risk factors reduced life expectancy at birth in 2005 by an estimated 4.9 y in men and 4.1 y in women. Life expectancy effects were smallest in Asians (M, 4.1 y; F, 3.6 y) and largest in Southern rural blacks (M, 6.7 y; F, 5.7 y). Standard deviation of life expectancies in the Eight Americas would decline by 0.50 y (18%) in men and 0.45 y (21%) in women if these risks had been reduced to optimal levels. Disparities in the probabilities of dying from cardiovascular diseases and diabetes at different ages would decline by 69%-80%; the corresponding reduction for probabilities of dying from cancers would be 29%-50%. Individually, smoking and high blood pressure had the largest effect on life expectancy disparities. CONCLUSIONS: Disparities in smoking, blood pressure, blood glucose, and adiposity explain a significant proportion of disparities in mortality from cardiovascular diseases and cancers, and some of the life expectancy disparities in the US. Please see later in the article for the Editors' Summary. PMID- 20351773 TI - Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species. AB - Changes in gene expression play an important role in evolution, yet the molecular mechanisms underlying regulatory evolution are poorly understood. Here we compare genome-wide binding of the six transcription factors that initiate segmentation along the anterior-posterior axis in embryos of two closely related species: Drosophila melanogaster and Drosophila yakuba. Where we observe binding by a factor in one species, we almost always observe binding by that factor to the orthologous sequence in the other species. Levels of binding, however, vary considerably. The magnitude and direction of the interspecies differences in binding levels of all six factors are strongly correlated, suggesting a role for chromatin or other factor-independent forces in mediating the divergence of transcription factor binding. Nonetheless, factor-specific quantitative variation in binding is common, and we show that it is driven to a large extent by the gain and loss of cognate recognition sequences for the given factor. We find only a weak correlation between binding variation and regulatory function. These data provide the first genome-wide picture of how modest levels of sequence divergence between highly morphologically similar species affect a system of coordinately acting transcription factors during animal development, and highlight the dominant role of quantitative variation in transcription factor binding over short evolutionary distances. PMID- 20351775 TI - Bayesian geostatistical modeling of Malaria Indicator Survey data in Angola. AB - The 2006-2007 Angola Malaria Indicator Survey (AMIS) is the first nationally representative household survey in the country assessing coverage of the key malaria control interventions and measuring malaria-related burden among children under 5 years of age. In this paper, the Angolan MIS data were analyzed to produce the first smooth map of parasitaemia prevalence based on contemporary nationwide empirical data in the country. Bayesian geostatistical models were fitted to assess the effect of interventions after adjusting for environmental, climatic and socio-economic factors. Non-linear relationships between parasitaemia risk and environmental predictors were modeled by categorizing the covariates and by employing two non-parametric approaches, the B-splines and the P-splines. The results of the model validation showed that the categorical model was able to better capture the relationship between parasitaemia prevalence and the environmental factors. Model fit and prediction were handled within a Bayesian framework using Markov chain Monte Carlo (MCMC) simulations. Combining estimates of parasitaemia prevalence with the number of children under we obtained estimates of the number of infected children in the country. The population-adjusted prevalence ranges from in Namibe province to in Malanje province. The odds of parasitaemia in children living in a household with at least ITNs per person was by 41% lower (CI: 14%, 60%) than in those with fewer ITNs. The estimates of the number of parasitaemic children produced in this paper are important for planning and implementing malaria control interventions and for monitoring the impact of prevention and control activities. PMID- 20351774 TI - Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Reduced saturated fat (SFA) consumption is recommended to reduce coronary heart disease (CHD), but there is an absence of strong supporting evidence from randomized controlled trials (RCTs) of clinical CHD events and few guidelines focus on any specific replacement nutrient. Additionally, some public health groups recommend lowering or limiting polyunsaturated fat (PUFA) consumption, a major potential replacement for SFA. METHODS AND FINDINGS: We systematically investigated and quantified the effects of increased PUFA consumption, as a replacement for SFA, on CHD endpoints in RCTs. RCTs were identified by systematic searches of multiple online databases through June 2009, grey literature sources, hand-searching related articles and citations, and direct contacts with experts to identify potentially unpublished trials. Studies were included if they randomized participants to increased PUFA for at least 1 year without major concomitant interventions, had an appropriate control group, and reported incidence of CHD (myocardial infarction and/or cardiac death). Inclusions/exclusions were adjudicated and data were extracted independently and in duplicate by two investigators and included population characteristics, control and intervention diets, follow-up duration, types of events, risk ratios, and SEs. Pooled effects were calculated using inverse-variance-weighted random effects meta-analysis. From 346 identified abstracts, eight trials met inclusion criteria, totaling 13,614 participants with 1,042 CHD events. Average weighted PUFA consumption was 14.9% energy (range 8.0%-20.7%) in intervention groups versus 5.0% energy (range 4.0%-6.4%) in controls. The overall pooled risk reduction was 19% (RR = 0.81, 95% confidence interval [CI] 0.70-0.95, p = 0.008), corresponding to 10% reduced CHD risk (RR = 0.90, 95% CI = 0.83-0.97) for each 5% energy of increased PUFA, without evidence for statistical heterogeneity (Q statistic p = 0.13; I(2) = 37%). Meta-regression identified study duration as an independent determinant of risk reduction (p = 0.017), with studies of longer duration showing greater benefits. CONCLUSIONS: These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD. Please see later in the article for the Editors' Summary. PMID- 20351776 TI - A community-based study of factors associated with continuing transmission of lymphatic filariasis in Leogane, Haiti. AB - Seven rounds of mass drug administration (MDA) have been administered in Leogane, Haiti, an area hyperendemic for lymphatic filariasis (LF). Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15.5%, suggesting that transmission had been reduced. A separate 30 cluster survey of 2- to 4-year-old children was conducted to determine if MDA interrupted transmission. Antigen and antifilarial antibody prevalence were 14.3% and 19.7%, respectively. Follow-up surveys were done in 6 villages, including those selected for the cluster survey, to assess risk factors related to continued LF transmission and to pinpoint hotspots of transmission. One hundred houses were mapped in each village using GPS-enabled PDAs, and then 30 houses and 10 alternates were chosen for testing. All individuals in selected houses were asked to participate in a short survey about participation in MDA, history of residence in Leogane and general knowledge of LF. Survey teams returned to the houses at night to collect blood for antigen testing, microfilaremia and Bm14 antibody testing and collected mosquitoes from these communities in parallel. Antigen prevalence was highly variable among the 6 villages, with the highest being 38.2% (Dampus) and the lowest being 2.9% (Corail Lemaire); overall antigen prevalence was 18.5%. Initial cluster surveys of 2- to 4-year-old children were not related to community antigen prevalence. Nearest neighbor analysis found evidence of clustering of infection suggesting that LF infection was focal in distribution. Antigen prevalence among individuals who were systematically noncompliant with the MDAs, i.e. they had never participated, was significantly higher than among compliant individuals (p<0.05). A logistic regression model found that of the factors examined for association with infection, only noncompliance was significantly associated with infection. Thus, continuing transmission of LF seems to be linked to rates of systematic noncompliance. PMID- 20351777 TI - Hepatitis B virus X protein impairs hepatic insulin signaling through degradation of IRS1 and induction of SOCS3. AB - BACKGROUND: Hepatitis B virus (HBV) is a major cause of chronic liver diseases, and frequently results in hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The role of HCV in associations with insulin signaling has been elucidated. However, the pathogenesis of HBV-associated insulin signaling remains to be clearly characterized. Therefore, we have attempted to determine the mechanisms underlying the HBV-associated impairment of insulin signaling. METHODOLOGY: The expressions of insulin signaling components were investigated in HBx-transgenic mice, HBx-constitutive expressing cells, and transiently HBx transfected cells. Protein and gene expression was examined by Western blot, immunohistochemistry, RT-PCR, and promoter assay. Protein-protein interaction was detected by coimmunoprecipitation. PRINCIPAL FINDINGS: HBx induced a reduction in the expression of IRS1, and a potent proteasomal inhibitor blocked the downregulation of IRS1. Additionally, HBx enhanced the expression of SOCS3 and induced IRS1 ubiquitination. Also, C/EBPalpha and STAT3 were involved in the HBx induced expression of SOCS3. HBx interfered with insulin signaling activation and recovered the insulin-mediated downregulation of gluconeogenic genes. CONCLUSIONS/SIGNIFICANCE: These results provide direct experimental evidences for the contribution of HBx in the impairment of insulin signaling. PMID- 20351778 TI - Development of low-cost inverted microscope to detect early growth of Mycobacterium tuberculosis in MODS culture. AB - BACKGROUND: The microscopic observation drug susceptibility (MODS) assay for rapid, low-cost detection of tuberculosis and multidrug resistant tuberculosis depends upon visualization of the characteristic cording colonies of Mycobacterium tuberculosis in liquid media. This has conventionally required an inverted light microscope in order to inspect the MODS culture plates from below. Few tuberculosis laboratories have this item and the capital cost of $5,000 for a high-end microscope could be a significant obstacle to MODS roll-out. METHODOLOGY: We hypothesized that the precise definition provided by costly high specification inverted light microscopes might not be necessary for pattern recognition. SIGNIFICANCE: In this work we describe the development of a low-cost artesenal inverted microscope that can operate in both a standard or digital mode to effectively replace the expensive commercial inverted light microscope, and an integrated system that could permit a local and remote diagnosis of tuberculosis. PMID- 20351779 TI - Genotyping of human lice suggests multiple emergencies of body lice from local head louse populations. AB - BACKGROUND: Genetic analyses of human lice have shown that the current taxonomic classification of head lice (Pediculus humanus capitis) and body lice (Pediculus humanus humanus) does not reflect their phylogenetic organization. Three phylotypes of head lice A, B and C exist but body lice have been observed only in phylotype A. Head and body lice have different behaviours and only the latter have been involved in outbreaks of infectious diseases including epidemic typhus, trench fever and louse borne recurrent fever. Recent studies suggest that body lice arose several times from head louse populations. METHODS AND FINDINGS: By introducing a new genotyping technique, sequencing variable intergenic spacers which were selected from louse genomic sequence, we were able to evaluate the genotypic distribution of 207 human lice. Sequence variation of two intergenic spacers, S2 and S5, discriminated the 207 lice into 148 genotypes and sequence variation of another two intergenic spacers, PM1 and PM2, discriminated 174 lice into 77 genotypes. Concatenation of the four intergenic spacers discriminated a panel of 97 lice into 96 genotypes. These intergenic spacer sequence types were relatively specific geographically, and enabled us to identify two clusters in France, one cluster in Central Africa (where a large body louse outbreak has been observed) and one cluster in Russia. Interestingly, head and body lice were not genetically differentiated. CONCLUSIONS: We propose a hypothesis for the emergence of body lice, and suggest that humans with both low hygiene and head louse infestations provide an opportunity for head louse variants, able to ingest a larger blood meal (a required characteristic of body lice), to colonize clothing. If this hypothesis is ultimately supported, it would help to explain why poor human hygiene often coincides with outbreaks of body lice. Additionally, if head lice act as a reservoir for body lice, and that any social degradation in human populations may allow the formation of new populations of body lice, then head louse populations are potentially a greater threat to humans than previously assumed. PMID- 20351780 TI - Cytosolic Hsp60 is involved in the NF-kappaB-dependent survival of cancer cells via IKK regulation. AB - Cytoplasmic presence of Hsp60, which is principally a nuclear gene-encoded mitochondrial chaperonin, has frequently been stated, but its role in intracellular signaling is largely unknown. In this study, we demonstrate that the cytosolic Hsp60 promotes the TNF-alpha-mediated activation of the IKK/NF kappaB survival pathway via direct interaction with IKKalpha/beta in the cytoplasm. Selective loss or blockade of cytosolic Hsp60 by specific antisense oligonucleotide or neutralizing antibody diminished the IKK/NF-kappaB activation and the expression of NF-kappaB target genes, such as Bfl-1/A1 and MnSOD, which thus augmented intracellular ROS production and ASK1-dependent cell death, in response to TNF-alpha. Conversely, the ectopic expression of cytosol-targeted Hsp60 enhanced IKK/NF-kappaB activation. Mechanistically, the cytosolic Hsp60 enhanced IKK activation via upregulating the activation-dependent serine phosphorylation in a chaperone-independent manner. Furthermore, transgenic mouse study showed that the cytosolic Hsp60 suppressed hepatic cell death induced by diethylnitrosamine in vivo. The cytosolic Hsp60 is likely to be a regulatory component of IKK complex and it implicates the first mitochondrial factor that regulates cell survival via NF-kappaB pathway. PMID- 20351781 TI - Dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape. AB - BACKGROUND: Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano-topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D) cell cultures. Cells anchored in a three-dimensional (3-D) microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D). METHODOLOGY/PRINCIPAL FINDINGS: Arrays of 5 or 10 microm deep microwells were fabricated in polydimethylsiloxane (PDMS). The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D) or trapped in microwells (3-D) of controlled size, shape, and wall rigidity. On rigid substrates (Young's Modulus = 1 MPa), cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area) and total surface areas of adhesion (microwell bottom plus wall surface area) that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detectable actin cytoskeleton in soft 3-D microwells (20 kPa), regardless of their shapes, but did so on flat, 2-D substrates. The dependency on environmental dimensionality was also reflected by cell viability and metabolism as probed by mitochondrial activities. Both were upregulated in 3-D cultured cells versus cells on 2-D patterns when surface area of adhesion and rigidity were held constant. CONCLUSION/SIGNIFICANCE: These data indicate that cell shape and rigidity are not orthogonal parameters directing cell fate. The sensory toolbox of cells integrates mechanical (rigidity) and topographical (shape and dimensionality) information differently when cell adhesions are confined to 2-D or occur in a 3-D space. PMID- 20351782 TI - Identification of a tsetse fly salivary protein with dual inhibitory action on human platelet aggregation. AB - BACKGROUND: Tsetse flies (Glossina sp.), the African trypanosome vectors, rely on anti-hemostatic compounds for efficient blood feeding. Despite their medical importance, very few salivary proteins have been characterized and functionally annotated. METHODOLOGY/PRINCIPAL FINDINGS: Here we report on the functional characterisation of a 5'nucleotidase-related (5'Nuc) saliva protein of the tsetse fly Glossina morsitans morsitans. This protein is encoded by a 1668 bp cDNA corresponding at the genomic level with a single-copy 4 kb gene that is exclusively transcribed in the tsetse salivary gland tissue. The encoded 5'Nuc protein is a soluble 65 kDa glycosylated compound of tsetse saliva with a dual anti-hemostatic action that relies on its combined apyrase activity and fibrinogen receptor (GPIIb/IIIa) antagonistic properties. Experimental evidence is based on the biochemical and functional characterization of recombinant protein and on the successful silencing of the 5'nuc translation in the salivary gland by RNA interference (RNAi). Refolding of a 5'Nuc/SUMO-fusion protein yielded an active apyrase enzyme with K(m) and V(max) values of 43+/-4 microM and 684+/-49 nmol Pi/min xmg for ATPase and 49+/-11 microM and 177+/-37 nmol Pi/min xmg for the ADPase activity. In addition, recombinant 5'Nuc was found to bind to GPIIb/IIIa with an apparent K(D) of 92+/-25 nM. Consistent with these features, 5'Nuc potently inhibited ADP-induced thrombocyte aggregation and even caused disaggregation of ADP-triggered human platelets. The importance of 5'Nuc for the tsetse fly hematophagy was further illustrated by specific RNAi that reduced the anti-thrombotic activities in saliva by approximately 50% resulting in a disturbed blood feeding process. CONCLUSIONS/SIGNIFICANCE: These data show that this 5'nucleotidase-related apyrase exhibits GPIIb/IIIa antagonistic properties and represents a key thromboregulatory compound of tsetse fly saliva. PMID- 20351783 TI - Strict de novo methylation of the 35S enhancer sequence in gentian. AB - A novel transgene silencing phenomenon was found in the ornamental plant, gentian (Gentiana triflora x G. scabra), in which the introduced Cauliflower mosaic virus (CaMV) 35S promoter region was strictly methylated, irrespective of the transgene copy number and integrated loci. Transgenic tobacco having the same vector did not show the silencing behavior. Not only unmodified, but also modified 35S promoters containing a 35S enhancer sequence were found to be highly methylated in the single copy transgenic gentian lines. The 35S core promoter (-90) introduced transgenic lines showed a small degree of methylation, implying that the 35S enhancer sequence was involved in the methylation machinery. The rigorous silencing phenomenon enabled us to analyze methylation in a number of the transgenic lines in parallel, which led to the discovery of a consensus target region for de novo methylation, which comprised an asymmetric cytosine (CpHpH; H is A, C or T) sequence. Consequently, distinct footprints of de novo methylation were detected in each (modified) 35S promoter sequence, and the enhancer region ( 148 to -85) was identified as a crucial target for de novo methylation. Electrophoretic mobility shift assay (EMSA) showed that complexes formed in gentian nuclear extract with the -149 to -124 and -107 to -83 region probes were distinct from those of tobacco nuclear extracts, suggesting that the complexes might contribute to de novo methylation. Our results provide insights into the phenomenon of sequence- and species- specific gene silencing in higher plants. PMID- 20351784 TI - Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni. AB - BACKGROUND: Previous studies suggest that humans can acquire immunity to reinfection with schistosomes, most probably due to immunologic mechanisms acquired after exposure to dying schistosome worms. METHODOLOGY/PRINCIPAL FINDINGS: We followed longitudinally two cohorts of adult males occupationally exposed to Schistosoma mansoni by washing cars (120 men) or harvesting sand (53 men) in Lake Victoria. Men were treated with praziquantel each time S. mansoni infection was detected. In car washers, a significant increase in resistance to reinfection, as measured by the number of cars washed between cure and reinfection, was observed after the car washers had experienced, on average, seven cures. In the car washers who developed resistance, the level of schistosome-specific IgE increased between baseline and the time at which development of resistance was first evidenced. In the sand harvesters, a significant increase in resistance, as measured by the number of days worked in the lake between cure and reinfection, was observed after only two cures. History of exposure to S. mansoni differed between the two cohorts, with the majority of sand harvesters being lifelong residents of a village endemic for S. mansoni and the majority of car washers having little exposure to the lake before they began washing cars. Immune responses at study entry were indicative of more recent infections in car washers and more chronic infections in sand harvesters. CONCLUSIONS/SIGNIFICANCE: Resistance to reinfection with S. mansoni can be acquired or augmented by adults after multiple rounds of reinfection and cure, but the rate at which resistance is acquired by this means depends on immunologic status and history of exposure to S. mansoni infection. PMID- 20351785 TI - Using recombinant proteins from Lutzomyia longipalpis saliva to estimate human vector exposure in visceral Leishmaniasis endemic areas. AB - BACKGROUND: Leishmania is transmitted by female sand flies and deposited together with saliva, which contains a vast repertoire of pharmacologically active molecules that contribute to the establishment of the infection. The exposure to vector saliva induces an immune response against its components that can be used as a marker of exposure to the vector. Performing large-scale serological studies to detect vector exposure has been limited by the difficulty in obtaining sand fly saliva. Here, we validate the use of two sand fly salivary recombinant proteins as markers for vector exposure. METHODOLOGY/PRINCIPAL FINDINGS: ELISA was used to screen human sera, collected in an area endemic for visceral leishmaniasis, against the salivary gland sonicate (SGS) or two recombinant proteins (rLJM11 and rLJM17) from Lutzomyia longipalpis saliva. Antibody levels before and after SGS seroconversion (n = 26) were compared using the Wilcoxon signed rank paired test. Human sera from an area endemic for VL which recognize Lu. longipalpis saliva in ELISA also recognize a combination of rLJM17 and rLJM11. We then extended the analysis to include 40 sera from individuals who were seropositive and 40 seronegative to Lu. longipalpis SGS. Each recombinant protein was able to detect anti-saliva seroconversion, whereas the two proteins combined increased the detection significantly. Additionally, we evaluated the specificity of the anti-Lu. longipalpis response by testing 40 sera positive to Lutzomyia intermedia SGS, and very limited (2/40) cross-reactivity was observed. Receiver-operator characteristics (ROC) curve analysis was used to identify the effectiveness of these proteins for the prediction of anti-SGS positivity. These ROC curves evidenced the superior performance of rLJM17+rLJM11. Predicted threshold levels were confirmed for rLJM17+rLJM11 using a large panel of 1,077 serum samples. CONCLUSION: Our results show the possibility of substituting Lu. longipalpis SGS for two recombinant proteins, LJM17 and LJM11, in order to probe for vector exposure in individuals residing in endemic areas. PMID- 20351786 TI - Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America. AB - BACKGROUND: Sand flies deliver Leishmania parasites to a host alongside salivary molecules that affect infection outcomes. Though some proteins are immunogenic and have potential as markers of vector exposure, their identity and vector specificity remain elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened human, dog, and fox sera from endemic areas of visceral leishmaniasis to identify potential markers of specific exposure to saliva of Lutzomyia longipalpis. Human and dog sera were further tested against additional sand fly species. Recombinant proteins of nine transcripts encoding secreted salivary molecules of Lu. longipalpis were produced, purified, and tested for antigenicity and specificity. Use of recombinant proteins corresponding to immunogenic molecules in Lu. longipalpis saliva identified LJM17 and LJM11 as potential markers of exposure. LJM17 was recognized by human, dog, and fox sera; LJM11 by humans and dogs. Notably, LJM17 and LJM11 were specifically recognized by humans exposed to Lu. longipalpis but not by individuals exposed to Lu. intermedia. CONCLUSIONS/SIGNIFICANCE: Salivary recombinant proteins are of value as markers of vector exposure. In humans, LJM17 and LJM11 emerged as potential markers of specific exposure to Lu. longipalpis, the vector of Leishmania infantum chagasi in Latin America. In dogs, LJM17, LJM11, LJL13, LJL23, and LJL143 emerged as potential markers of sand fly exposure. Testing these recombinant proteins in large scale studies will validate their usefulness as specific markers of Lu. longipalpis exposure in humans and of sand fly exposure in dogs. PMID- 20351787 TI - Risk factors for anthroponotic cutaneous Leishmaniasis at the household level in Kabul, Afghanistan. AB - BACKGROUND: Kabul, Afghanistan, is the largest focus of anthroponotic cutaneous leishmaniasis (ACL) in the world. ACL is a protozoan disease transmitted to humans by the bite of phlebotomine sand flies. Although not fatal, ACL can lead to considerable stigmatization of affected populations. METHODS: Using data from a standardized survey of 872 households in 4 wards of Kabul, Afghanistan, univariate and multivariate logistic regression analyses tested associations between presence of active ACL and ACL scars with 15 household-level variables. FINDINGS: Univariate analyses showed that active ACL was positively associated with household member's age, ACL prevalence, and brick wall type, but negatively associated with household number of rooms, bednet use, and proportion of windows with screens. Multivariate analysis showed a positive association between active ACL and household member's age, ACL prevalence, and brick wall type, and a negative association with household proportion of windows with screens. CONCLUSION: Household-level characteristics were shown to be risk factors for ACL. Monitoring a selected number of household characteristics could assist in rapid assessments of household-level variation in risk of ACL. ACL prevention and control programs should consider improving house construction, including smoothing of walls and screening of windows. PMID- 20351789 TI - The Ethics of the Treatment of Spinal Cord Injury: Stem Cell Transplants, Motor Neuroprosthetics, and Social Equity. AB - The intense desire for a "cure" in individuals with spinal cord injury (SCI) has resulted in the transplantation of stem cells and embryonic and other cell types into the injured spinal cord to enable limb function. We review the ethical issues concerning the procurement and use of embryonic stem cells. A brief survey of the current state of human SCI transplantation is presented. We explore the interface between basic science and the clinical management of SCI and discuss the ethical issues of therapy. At what point is it ethical to conduct human experiments when the experimental data is still at an early stage of development? Is it ethical to perform these operations on a vulnerable group of patients without adequate scientific controls and analysis of the results? Motor neuroprosthetics is developing rapidly and will enable limb movement controlled by the paralyzed patient and other device control such as wheelchairs and communication boards. How can there be a more equitable distribution of such expensive technology and other treatments of SCI? Both clinicians and scientists should be mindful of these complex ethical issues when undertaking pioneering therapies for patients with SCI. PMID- 20351788 TI - Routes to lenition: an acoustic study. AB - BACKGROUND: Vowel lenition and its link with coarticulation have been the subject of extensive debate in the literature. The aims of the present paper are to demonstrate how vowel lenition and coarticulation are linked in Cypriot Greek (henceforth CG), to determine the nature of vowel lenition, and to illustrate how vowel lenition and coarticulation result from aerodynamic phenomena. METHODOLOGY/PRINCIPAL FINDINGS: Eight speakers were recorded producing utterances ending in either /i/ or /u/. Acoustic measures such as V(1)F2 and stop duration were employed to determine whether lenition of the vowels results in coarticulation with the preceding consonant. Results show that there is extensive stop-vowel coarticulation in CG and that stop production is as variable as vowel production, with full vowels never co-occurring with canonical consonants, indicating the existence of two routes to lenition in CG. CONCLUSIONS/SIGNIFICANCE: These findings suggest that lenition in the final syllable is a consequence of the supralaryngeal articulation coupled with a marginal glottal setting. PMID- 20351790 TI - Determinants of primary care physicians' referral pattern: a structural equation model approach. AB - This study examines patient referrals by primary care physicians (PCP) with nurse practitioners and physician assistants (NP-PA) in their medical practices as compared to practices without them. The study uses data from the Robert Wood Johnson Foundation community tracking study (CTS) Physician Survey, Round I (1996 97) and II (1998-99). Structural equations with binary dependent variables were used to examine the links among managed care, the use of NP-PA, the complexity of patient's conditions, and the number of referrals. PCP's with NP-PA were found to have a greater likelihood of treating patients with complex conditions instead of referring them to specialists. Managed care related variables (i.e., large group practice/HMO, the percentage of patients for whom PCPs acted as gatekeepers, and the percentage of managed care revenue from capitated/prepaid contracts) affected PCP' patient referrals, but only through the increased use of NP-PA. PCP's with NP-PA were also found to provide appropriate care to the complex patients. These findings indicate that NP-PA enable PCP to concentrate on patients with more complex conditions thus reducing the number of referrals. In addition, NP-PA is found to affect the gatekeeper role of PCPs. PMID- 20351791 TI - An Enantioselective Synthesis of the ABD Tricycle for (-)-Phomactin A Featuring Rawal's Asymmetric Diels-Alder Cycloaddition. AB - An enantioselective synthesis of the ABD-ring of (-)-phomactin A is described here. The sequence features Rawal's asymmetric Diels-Alder cycloaddition. The overall length is significantly reduced from our previous attempt. PMID- 20351793 TI - Learning accurate and concise naive Bayes classifiers from attribute value taxonomies and data. AB - In many application domains, there is a need for learning algorithms that can effectively exploit attribute value taxonomies (AVT)-hierarchical groupings of attribute values-to learn compact, comprehensible and accurate classifiers from data-including data that are partially specified. This paper describes AVT-NBL, a natural generalization of the naive Bayes learner (NBL), for learning classifiers from AVT and data. Our experimental results show that AVT-NBL is able to generate classifiers that are substantially more compact and more accurate than those produced by NBL on a broad range of data sets with different percentages of partially specified values. We also show that AVT-NBL is more efficient in its use of training data: AVT-NBL produces classifiers that outperform those produced by NBL using substantially fewer training examples. PMID- 20351792 TI - Effects of Delta-THC on Working Memory: Implications for Schizophrenia? AB - This article reviews the literature on the acute effects of Delta 9 tetrahydrocannabinol, the primary psychoactive component of marijuana, on working memory, and the implications for schizophrenia. Working memory deficits are a hallmark feature of schizophrenia, and have been implicated as an etiologic mechanism contributing to the onset of the disorder. Regular marijuana smokers may also exhibit subtle working memory impairment relative to healthy controls, and an association between marijuana abuse and subsequent development of schizophrenia, though controversial, has been reported in the literature. The causal role that marijuana plays in working memory impairment related to schizophrenia, however, remains unclear. Thus, this article specifically considers the acute effects of marijuana on working memory performance. The ecologic relevance and clinical significance of these findings will be examined, and directions for future research will be recommended. PMID- 20351794 TI - The Effect of Alcohol Consumption on Mortality: Regression Discontinuity Evidence from the Minimum Drinking Age. AB - We estimate the effect of alcohol consumption on mortality using the minimum drinking age in a regression discontinuity design. We find large and immediate increases in drinking at age 21, including a 21 percent increase in recent drinking days. We also find a discrete 9 percent increase in the mortality rate at age 21, primarily due to motor vehicle accidents, alcohol-related deaths, and suicides. We estimate a 10 percent increase in the number of drinking days for young adults results in a 4.3 percent increase in mortality. Our results suggest policies that reduce drinking among young adults can have substantial public health benefits. (JEL I12, I18). PMID- 20351795 TI - TRAINING OLDER WORKERS FOR TECHNOLOGY-BASED EMPLOYMENT. AB - An increasingly aging workforce and advances in technology are changing work environments and structures. The continued employability of older adults, particularly those of lower socioeconomic status (SES), requires them to participate in training programs to ensure their competence in today's workplace. Focus groups with 37 unemployed adults (51-76 years old) were conducted to gather information about barriers and obstacles for returning to work, training needs and formats, work experiences, and perceptions of the characteristics of an ideal job. Overall, results indicated that participants experienced age discrimination and lack of technology skills. They also expressed a desire to receive additional training on technology and a preference for classroom training. PMID- 20351796 TI - Homeless Women's Personal Networks: Implications for Understanding Risk Behavior. AB - The goal of this exploratory study was to examine the composition of homeless women's personal networks in order to better understand the social context of risk behavior in this vulnerable population. Twenty-eight homeless women residing in temporary shelters in Los Angeles County provided detailed information about their extended personal networks. Women named 25 people with whom they had contact during the past year, and then were asked a series of questions about each one of these named network members. Results indicate that the personal networks of homeless women are larger and more diverse than suggested by previous research. About one-third of women's relationships were with high-risk individuals (i.e., people perceived to drink heavily, use drugs, or engage in risky sex). However, most women also reported having relationships that could be characterized as both "low risk" (e.g., involving individuals perceived as not drinking heavily, using drugs, or engaging in risky sex) and "high quality" (e.g., long-term, emotionally close, or supportive), although these relationships tended to be rather tenuous. Our results suggest a need to assist homeless women in strengthening these existing low-risk/high-quality relationships, and extending the diversity of their networks, in order to increase women's exposure to positive role models and access to tangible support and other needed resources. PMID- 20351797 TI - Protrusion of a Virtual Model Lamellipodium by Actin Polymerization: A Coarse grained Langevin Dynamics Model. AB - We report the development of a coarse-grained Langevin dynamics model of a lamellipodium featuring growing F-actin filaments in order to study the effect of stiffness of the F-actin filament, the G-actin monomer concentration, and the number of polymerization sites on lamellipodium protrusion. The virtual lamellipodium is modeled as a low-aspect-ratio doubly capped cylinder formed by triangulated particles on its surface. It is assumed that F-actin filaments are firmly attached to a lamellipodium surface where polymerization sites are located, and actin polymerization takes place by connecting a G-actin particle to a polymerization site and to the first particle of a growing F-actin filament. It is found that there is an optimal number of polymerization sites for rapid lamellipodium protrusion. The maximum speed of lamellipodium protrusion is related to competition between the number of polymerization sites and the number of available G-actin particles, and the degree of pulling and holding of the lamellipodium surface by non-polymerizing actin filaments. The lamellipodium protrusion by actin polymerization displays saltatory motion exhibiting pseudo thermal equilibrium: the lamellipodium speed distribution is Maxwellian in two dimensions but the lamellipodium motion is biased so that the lamellipodium speed in the direction of the lamellipodium motion is much larger than that normal to the lamellipodium motion. PMID- 20351798 TI - A Framework for Learning from Distributed Data Using Sufficient Statistics and its Application to Learning Decision Trees. AB - This paper motivates and precisely formulates the problem of learning from distributed data; describes a general strategy for transforming traditional machine learning algorithms into algorithms for learning from distributed data; demonstrates the application of this strategy to devise algorithms for decision tree induction from distributed data; and identifies the conditions under which the algorithms in the distributed setting are superior to their centralized counterparts in terms of time and communication complexity; The resulting algorithms are provably exact in that the decision tree constructed from distributed data is identical to that obtained in the centralized setting. Some natural extensions leading to algorithms for learning from heterogeneous distributed data and learning under privacy constraints are outlined. PMID- 20351799 TI - THE TRANSMISSION AND PERSISTENCE OF 'URBAN LEGENDS': SOCIOLOGICAL APPLICATION OF AGE-STRUCTURED EPIDEMIC MODELS. AB - This paper describes two related epidemic models of rumor transmission in an age structured population. Rumors share with communicable disease certain basic aspects, which means that formal models of epidemics may be applied to the transmission of rumors. The results show that rumors may become entrenched very quickly and persist for a long time, even when skeptics are modeled to take an active role in trying to convince others that the rumor is false. This is a macrophenomeon, because individuals eventually cease to believe the rumor, but are replaced by new recruits. This replacement of former believers by new ones is an aspect of all the models, but the approach to stability is quicker, and involves smaller chance of extinction, in the model where skeptics actively try to counter the rumor, as opposed to the model where interest is naturally lost by believers. Skeptics hurt their own cause. The result shows that including age, or a variable for which age is a proxy (e.g., experience), can improve model fidelity and yield important insights. PMID- 20351800 TI - A Design-Adaptive Local Polynomial Estimator for the Errors-in-Variables Problem. AB - Local polynomial estimators are popular techniques for nonparametric regression estimation and have received great attention in the literature. Their simplest version, the local constant estimator, can be easily extended to the errors-in variables context by exploiting its similarity with the deconvolution kernel density estimator. The generalization of the higher order versions of the estimator, however, is not straightforward and has remained an open problem for the last 15 years. We propose an innovative local polynomial estimator of any order in the errors-in-variables context, derive its design-adaptive asymptotic properties and study its finite sample performance on simulated examples. We provide not only a solution to a long-standing open problem, but also provide methodological contributions to error-invariable regression, including local polynomial estimation of derivative functions. PMID- 20351801 TI - APPLICATION OF PREPARATIVE HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY FOR SEPARATION OF ELATINE FROM DELPHINIUM SHAWURENSE. AB - Preparative separation of elatine in Delphinium shawurense was achieved for the first time using high-speed countercurrent chromatography (HSCCC). The separation was performed with a solvent system composed of ethyl acetate-chloroform-methanol water (3:0.1:2:3, v/v) using the lower organic phase as a mobile phase under a revolution speed of 800 rpm. This yielded 72 mg of elatine at over 97% purity with an approximately 95% recovery. The chemical structure was identified by MS and NMR. PMID- 20351802 TI - ISOLATION AND PUNRIFICATION OF PSORALEN AND BERGAPTEN FROM FICUS CARICA L LEAVES BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY. AB - High-speed countercurrent chromatography was successfully applied for the first time for the separation of psoralen and bergapten from Ficus carica L leaves. The crudeextract obtained by light petroleum (b.p.: 60 degrees C-90 degrees C) from the dried leaves of Ficus carica L. was separated with a two-phase solvent system of n-Hexane-ethyl acetate-methanol-water (1:1:1:1, v/v). Each peak fraction was analyzed by high-performance liquid chromatography. The method yielded 4.4 mg of psoralen at 99.1% purity and 2.1 mg of bergapten at 98.2% purity from 400 mg of the crude extract in a single run. The two compounds were identified by (1)H-NMR, (13)C-NMR and MS. PMID- 20351803 TI - Hemolytic uremic syndrome after renal transplantation. AB - Hemolytic Uremic Syndrome after kidney transplantation affects an increasing number of patients. It is characterized as recurrent and de novo. Older age at onset of HUS, shorter mean interval between HUS and transplantation or ESRD, living related donor and treatment with CNI have been associated with an increased risk of recurrence. Patients who lost the first transplant because of HUS recurrence should not receive a second transplant. The outcome of recurring HUS after transplantation is worse in familial forms leading invariably to graft loss and for this reason doctors should discourage the use of living related donors in this setting. De novo HUS is not a rare complication after kidney transplantation and may be associated with infection, CNI or mTOR inhibitor toxicity, antibody use (OKT3), or acute vascular rejection. The clinical picture is obscure and treatment rests on removal of inciting factor with or without plasma exchange/FFP infusion. PMID- 20351804 TI - Late pregnancy complications in polycystic ovarian syndrome. AB - Gestational diabetes mellitus and new-onset hypertension, which includes gestational hypertension and pre-eclampsia, are common complications of pregnancy. Many features of the insulin resistance syndrome have been associated with these conditions. These include glucose intolerance, hyperinsulinemia, hypertension, obesity, and lipid abnormalities. Other accompanying abnormalities may include elevated serum levels of leptin, TNFalpha, plasminogen activator inhibitor-1 and testosterone. The establishment of these features before the onset of gestational diabetes mellitus and hypertension in pregnancy suggests that insulin resistance or associated abnormalities may play a role in these disorders. These observations suggest that therapeutic interventions to reduce insulin resistance may lower the risk of both gestational diabetes mellitus and hypertension in pregnancy. PMID- 20351805 TI - RNA Intereference: a powerful laboratory tool and its therapeutic implications. AB - Ever since RNA interference (RNAi) was discovered in the early 1990s, a number of scientists from the academic and biotechnology world have continued to view it as the revolutionary discovery of the century. Unequivocally, RNAi can be considered as an important regulator of gene expression in many eukaryotic cells. The term RNAi describes a natural process by which a double-stranded RNA molecule, when introduced into the cell is processed into short RNA duplexes and drives gene silencing by specific and distinct mechanisms. Many of the players involved in this cellular defense network have been elucidated but a more complete understanding of the process is essential. Worldwide interest on RNAi in the last decade is mainly attributed to its power as a laboratory tool for the experimental manipulation of gene expression. RNAi assisted already in the dissection of numerous cellular pathways and revealed the role of many proteins in an approach aimed to drug discovery. This new technology has the potential to improve our understanding of physiologic and pathologic processes and lead to the discovery of new drugs. More importantly, there is growing interest among the scientific community for the potential therapeutic applications of RNAi. PMID- 20351806 TI - What's new in p53? AB - p53 is the main intrinsic factor inducing apoptosis by recognizing the external stimuli and activating the p53 responsive genes to an irreversible series of events. P53 activates the transcription of specific proapoptotic genes called p53 target genes. A growing number of p53 responsive genes have been identified and numerous studies have demonstrated that p53 proapoptotic factors such as Noxa, Puma and Perp play cell type specific roles in p53's mediated response to certain stimuli. Perp (p53 apoptosis effector related to PMP-22) is a direct proapoptotic target gene encoding a tetraspan protein. Perp is highly expressed in cells undergoing apoptosis compared to cells under G1 arrest and its overexpression is sufficient to cause cell death in fibroblasts. Noxa is another member of the preapoptotic p53 genes family. When expressed Noxa acts in a BH3 motif-dependent localization to mitochondria, causing structural changes, activation of caspase 9 and release of cytochrome c from mitochondria to cytosol. Puma (p53 mutant of apoptosis) is another critical mediator of p53-dependent apoptosis. P53 binds to Puma-promoter gene sites, leading to puma production. The mtCLIC, a member of intracellular chloride channels, is a cytoplasmic and mitochondrial protein positively regulated by p53. Caspase 10 is induced in p53-dependent manner leading to cellular apoptosis. Other newly announced factors are also involved in p53-regulated apoptosis such as brain-specific angiogenesis inhibitor-1 (BSAI1), MSOD and GPX genes. A global discussion on this topic is attempted in the present review article. PMID- 20351808 TI - Regulation of the FOXM1 transcription factor by the estrogen receptor alpha at the protein level, in breast cancer. AB - Breast cancer is the most frequent type of cancer of women in the western world. Antiestrogens, including Tamoxifen (OHT) and Faslodex (ICI), are widely used in the endocrine treatment of breast cancer. However, the majority of breast cancers are either resistant to endocrine therapy or eventually become unresponsive to antiestrogen therapy. Better understanding of the molecular mechanisms that govern tumour proliferation, is therefore needed to develop new therapies for the disease. The Forkhead family of transcription factors plays an important role in regulating cell proliferation, cell death and differentiation.The estrogen receptor (ER) a positive breast carcinoma cell line MCF-7 and the ERa negative line MDA-MB-231 was used to study the potential regulation of the Forkhead member FOXM1 by ER. It was indicated that estrogen and ER regulate the expression of FOXM1 at the protein level. Since Forkhead proteins play an important role in regulating cell proliferation, cell death and differentiation, this study helps to explain some of the functions of ER in tumourigenesis, and the way these Forkhead proteins could be crucial targets for therapeutic strategies and/or markers for diagnosis and prognosis. PMID- 20351807 TI - Anovulation and ovulation induction. AB - Conventional treatment of normogonadotropic anovulatory infertility is ovulation induction using the antiestrogen clomiphene citrate, followed by follicle stimulating hormone. Multiple follicle development, associated with ovarian hyperstimulation, and multiple pregnancy remain the major complications. Cumulative singleton and multiple pregnancy rate data after different induction treatments are needed. Newer ovulation induction interventions, such as insulin sensitizing drugs, aromatase inhibitors and laparoscopic ovarian electrocoagulation, should be compared with conventional treatments. Ovulation induction efficiency might improve if patient subgroups with altered chances for success or complications with new or conventional techniques could be identified, using multivariate prediction models based on initial screening characteristics. This would make ovulation induction more cost-effective, safe and convenient, enabling doctors to advise patients on the most effective and patient-tailored treatment strategy. PMID- 20351809 TI - Diagnostic value of the Conventional and Doppler ultrasound in pregnancy complicated with preeclampsia. AB - BACKGROUND: Preeclampsia (PE) is a pregnancy complication usually of the third trimester. The clinical manifestations are hypertension and proteinuria with or without edema. Its pathogenesis is characterized by generalized vasoconstriction and endothelial dysfunction. The aim of this study was to evaluate the diagnostic value of the Doppler ultrasound examination of the renal interlobar vessels in pregnancy complicated with preeclampsia in the context of the theory about the increased vessel resistance in this pregnancy disorder. METHODS: Fifty two women aged 16-38, (mean age 23+/-9.54) streamed into three groups were examined by abdominal ultrasound in Triplex regime. The first group included 18 pregnant with PE, the second 21 women in the third trimester of normal pregnancy, and the third group 13 non-pregnant women. In all 3 groups the renal volume (RV) and parenchyma volume (PV) were determined by conventional ultrasound (CU). The doppler waveform analysis (DWA) of the interlobar renal arteries (IRA) gave the following indices: resistance index (RI), pulsatility index (PI), peak systolic velocity (Vmax) and end diastolic velocity (Vmin). RESULTS. RV and PV in the PE group were significantly higher then those of the healthy pregnant women: RV: 231.4+/-58 to 187+/-45, p<0.05 and for PV: 200+/-11 to 130+/-6.78, p<0.05. Such a difference was not found out for the healthy pregnant women compared to the non-pregnant ones. No significant differences of the examined doppler indices were found in the three groups. CONCLUSION: Although the arteriolar vasoconstriction and the tissue hypoxia are leading in the PE pathogenesis, the DWA of the IRA in PE pregnancy does not differ from those of the healthy pregnant and nonpregnant women. As one of the most frequently used imaging technique Doppler Ultrasound (DU) of the renal IRA and DWA of these vessels shows no diagnostic advantage as compared to the renal CU in pregnancy complicated with PE. PMID- 20351810 TI - Pulmonary embolism: CT findings with the use of helical computed tomography. AB - AIM: The aim of this study is the presentation of the imaging findings in patients with pulmonary embolism, the diagnosis of which was made with the use of helical computed tomography. MATERIAL AND METHODS: The lung CT scans of 14 patients were retrospectively studied. The presence of hypoattenuating thrombus within the lumen of one or more pulmonary arterial branches was considered as the imaging criterion for the diagnosis of pulmonary embolism. RESULTS: Emboli within the lumen of 1st order branches were found in 2 patients, within the lumen of 2nd order branches in 8 patients, into the lumen of 3rd order branches (lobar) in 10 patients and into the lumen of 4th order branches (segmental) in 6 patients. No emboli were detected in subsegmental or more peripheral branches. Concomitant, secondary findings were the presence of unilateral pleural effusion, areas of pulmonary oligaemia and the presence of a wedge-shaped, pleural-based opacity, indicative of a pulmonary infarct. CONCLUSION: In conclusion, we were able to make the diagnosis of pulmonary embolism through the direct visualization of intraluminal emboli up until the segmental level, as well as of concomitant, accessory findings of pulmonary embolism. PMID- 20351811 TI - Peripheral activities during EMR use in emergency care: a case study. AB - We report on how the use of electronic medical record (EMR) systems in an emergency department (ED) contributes to peripheral physician activities and in turn, how these peripheral activities can lead to challenges in the patient care process. Through a qualitative research study, we identify three prominent peripheral activities that affect the continuity of care: (1) transition between multiple artifacts, (2) movement between multiple locations and (3) transition of information between multiple care providers. We discuss how the peripheral activities can introduce new errors and create bottlenecks in patient flow, consequently affecting both clinical and organizational goals. We highlight the importance of integrating EMR applications with the model of practice in the ED. PMID- 20351812 TI - FigSum: automatically generating structured text summaries for figures in biomedical literature. AB - Figures are frequently used in biomedical articles to support research findings; however, they are often difficult to comprehend based on their legends alone and information from the full-text articles is required to fully understand them. Previously, we found that the information associated with a single figure is distributed throughout the full-text article the figure appears in. Here, we develop and evaluate a figure summarization system - FigSum, which aggregates this scattered information to improve figure comprehension. For each figure in an article, FigSum generates a structured text summary comprising one sentence from each of the four rhetorical categories - Introduction, Methods, Results and Discussion (IMRaD). The IMRaD category of sentences is predicted by an automated machine learning classifier. Our evaluation shows that FigSum captures 53% of the sentences in the gold standard summaries annotated by biomedical scientists and achieves an average ROUGE-1 score of 0.70, which is higher than a baseline system. PMID- 20351813 TI - Using electronic data sources to understand the determinants of psychiatric visit non-adherence. AB - Technology cannot be effectively used to drive improvements in health care quality and health care cost reduction until significantly more healthcare visits are attended. Visit attendance is often perceived as an intractable problem. This formative study identified and analyzed a set of visit adherence determinants to delineate a structure of adherence. The study is distinguished from previous work because it employs three types of determinants (socio-economic, diagnosis, and logistical), captured from an ADT system and an EMR, to predict visit non adherence. PMID- 20351814 TI - Opportunities for informatics to improve discharge planning: a systematic review of the literature. AB - The discharge planning process can be successful when information is shared among the patient, caregiver, and provider from admission through post discharge. The objective of this paper was to evaluate the association of information sharing among patients, caregivers, and health care providers and the impact on the discharge process. The authors identified reports of the discharge planning process through systematic electronic database searches. The eligibility criteria were 1) usual discharge planning process, and 2) patient, caregiver, or provider perception or feedback. Of the eligible articles, all voiced concern about a broken discharge planning process that affected the information exchanged among all involved in patient care. Outcomes related to satisfaction, knowledge transfer, and communication were identified. The initial evidence suggests information sharing through interdisciplinary patient care can play a significant role in the future. PMID- 20351815 TI - Heralding new ringtones of patient safety: Blackberry-based clinical communication and telementoring in laparoscopic surgery. PMID- 20351816 TI - Evaluation of a prototype search and visualization system for exploring scientific communities. AB - Searches of bibliographic databases generate lists of articles but do little to reveal connections between authors, institutions, and grants. As a result, search results cannot be fully leveraged. To address this problem we developed Sciologer, a prototype search and visualization system. Sciologer presents the results of any PubMed query as an interactive network diagram of the above elements. We conducted a cognitive evaluation with six neuroscience and six obesity researchers. Researchers used the system effectively. They used geographic, color, and shape metaphors to describe community structure and made accurate inferences pertaining to a) collaboration among research groups; b) prominence of individual researchers; and c) differentiation of expertise. The tool confirmed certain beliefs, disconfirmed others, and extended their understanding of their own discipline. The majority indicated the system offered information of value beyond a traditional PubMed search and that they would use the tool if available. PMID- 20351817 TI - A temporal abstraction framework for classifying clinical temporal data. AB - The increasing availability of complex temporal clinical records collected today has prompted the development of new methods that extend classical machine learning and data mining approaches to time series data. In this work, we develop a new framework for classifying the patient's time-series data based on temporal abstractions. The proposed STF-Mine algorithm automatically mines discriminative temporal abstraction patterns from the data and uses them to learn a classification model. We apply our approach to predict HPF4 test orders from electronic patient health records. This test is often prescribed when the patient is at the risk of Heparin induced thrombocytopenia (HIT). Our results demonstrate the benefit of our approach in learning accurate time series classifiers, a key step in the development of intelligent clinical monitoring systems. PMID- 20351818 TI - A multi-lingual web service for drug side-effect data. AB - In this paper, we describe a system that provides drug side-effect data for use as a component in service-oriented architectures. Our system uses "Web 2.0" techniques to collect data from a variety of public sources, and can provide its output in a variety of human languages (e.g. Spanish and Arabic). To demonstrate our tool's versatility and the ease with which it may be integrated into larger systems, we present several front-ends that use our system, including SMS ("text message"), "instant messenger", and iPhone interfaces. We enlisted a panel of Argentinean clinicians to review and rate the quality of our system's Spanish language output in order to investigate whether freely-available general-purpose machine translation technology (Google's translation API) is adequate for consumer medical applications. Our raters found that Google's translation quality varied greatly among drugs, and we conclude that it is better used as a starting point than as a complete translation solution. PMID- 20351819 TI - User centered design in complex healthcare workflows: the case of care coordination and care management redesign. AB - We present the User Need Analysis process for the Integrated Care Coordination Information System (ICCIS) research project at Oregon Health & Science University (OHSU). The primary goal of the process was to select a mix of methodologies to perform user need analysis which would lead to generation of system requirements. The ICCIS Team developers would use these prioritized requirements to build the next generation of the ICCIS software that would help meet the overall goals of the care model. First, semi-structured User Discussion Guides and structured questioners were used to collect raw needs from Physicians, Nurses, IT and Administrative personal. Later Conjoint Analysis (CA) and Dimensional Analysis (DA) were used to generate emerging concepts and priorities from the discussions with the end-user community. PMID- 20351821 TI - Quantifying temporal documentation patterns in clinician use of AHLTA-the DoD's ambulatory electronic health record. AB - In this paper, we analyzed computer-recorded user interactions with AHLTA, the electronic health record (EHR) used by the Department of Defense, to study clinicians' temporal documentation behavior in their use of the system in their daily clinical practice. We collected one week of AHLTA usage data via a monitoring software program installed in 35,570 clinical workstations across 138 military treatment facilities. The data allowed us to quantify the temporal relations among sentinel events that represent two distinct phases of clinical documentation: initiating a patient encounter and finalizing the patient note. The results suggest that alternative EHR documentation strategies such as deferred documentation were commonly employed by clinicians. The incidence rates of encounter initiation and finalization were significantly disproportional across time of day. Lunchtime and late afternoon catch-up activities were clearly delineated. While alternative documentation is a known tactic employed by clinicians, it has not been rigorously quantified in previous research. PMID- 20351820 TI - Using SNOMED CT in combination with MedDRA for reporting signal detection and adverse drug reactions reporting. AB - OBJECTIVE: To investigate the feasibility of using SNOMED CT as an entry point for coding adverse drug reactions and map them automatically to MedDRA for reporting purposes and interoperability with legacy repositories. METHODS: On the one hand, we attempt to map SNOMED CT concepts to MedDRA concepts through the UMLS, using synonymy and explicit mapping relations. On the other, we compute the set of all fine-grained concepts that can be reached from concepts having a mapping to MedDRA. RESULTS: 58% of the Preferred Terms in MedDRA have a mapping to SNOMED CT. Through the descendants in SNOMED CT, 108,305 additional SNOMED CT concepts can be linked to MedDRA. CONCLUSIONS: Fine-grained SNOMED CT concepts can be mapped automatically to MedDRA. This approach has the potential to enable the collection of adverse events related to drugs directly from clinical repositories. The quality of the mapping needs to be evaluated. PMID- 20351822 TI - From prototype to production: lessons learned from the evolution of an EHR educational portal. AB - The use of electronic health records is rapidly increasing. However, the integration of this technology into the education of health professionals and health informaticians has largely remained to be explored. In this paper we describe an approach to providing remote access to electronic health records for use in health professional and health informatics education at the undergraduate and graduate levels. The University of Victoria EHR Educational Portal was designed by the authors to allow for remote Web-based access by students to a range of systems hosted on the portal. Architectural considerations and the evolution of the portal structure from prototype to production system are described. The paper also describes our initial applications of the approach in integrating EHRs into nursing, medical and health informatics educational programs. PMID- 20351823 TI - Consequences of the verification of completeness in clinical practice guideline modeling: a theoretical and empirical study with hypertension. AB - Building clinical decision support systems requires a formalization of clinical practice guidelines (CPGs) including the verification of completeness to ensure all medically relevant situations are addressed. Recommendations that rely on completed knowledge cannot be but expert-based. Using French hypertension management guidelines, we characterized the status of a patient profile as evidence-based (EB), consensus-based (CB), or expert-based (XB). The distribution of these status on the formal patient profiles of ASTIGM knowledge base showed that 12.6% (0.5% EB and 12.1% CB) lead to explicit CPG recommendations. The same analysis on a sample of 435 actual patients medical records showed that 55% were covered by CPGs. The characterization of guideline-based CDSSs should be based on empirical data estimated from the target population of CPGs. PMID- 20351824 TI - Mychildren's: integration of a personally controlled health record with a tethered patient portal for a pediatric and adolescent population. AB - Personally controlled health records (PCHRs) and patient portals are increasingly being offered by healthcare institutions, employers, insurance companies and commercial entities to allow patients access to their health information. Both applications offer unique services to provide patients with tools to manage their health. While PCHRs allow users ubiquitous, portable, patient controlled access to their health information, traditional patient portals provide provider tethered applications allowing patients access, but not control of, certain healthcare information, as well as communication and administrative functions, such as secure messaging, appointment management and prescription refill requests, facilitating care at a specific healthcare facility.We describe our approach for the design, content creation, policy development, and implementation of MyChildren's, a unique web-based application leveraging the advantages of both a provider-tethered patient portal and a PCHR to allow patients and their guardians access to the functionality and convenience of a traditional patient portal, as well as the portability and flexibility of a PCHR. PMID- 20351825 TI - Architecture of a federated query engine for heterogeneous resources. AB - The Federated Utah Research and Translational Health e-Repository (FURTHeR) is a Utah statewide informatics platform for the new Center for Clinical and Translational Science at the University of Utah. We have been working on one of FURTHeR's key components, a federated query engine for heterogeneous resources, that we believe has the potential to meet some of the fundamental needs of translational science to access and integrate diverse biomedical data and promote discovery of new knowledge. The architecture of the federated query engine for heterogeneous resources is described and demonstrated. PMID- 20351826 TI - Two approaches to integrating phenotype and clinical information. AB - Linkages between animal models of diseases and human data enable the development of translational research hypotheses. The objective of this study is to investigate two approaches to integrating phenotype and clinical information. On the one hand, we develop a terminology mapping between phenotypes from the Mammalian Phenotype Ontology (MPO) and Online Mendelian Inheritance in Man (OMIM) through the Unified Medical Language System (UMLS). On the other, we associate MPO phenotypes with OMIM manifestations through annotations made to orthologous genes. 1,469 MPO concepts (22%) were mapped successfully to some disease concept in the UMLS, of which 869 were present in OMIM. Among the 16,764 distinct MGI genes associated with human orthologs, 1,968 distinct genes were associated with both MPO and OMIM annotations. The UMLS is a valuable resource for linking phenotype terms to clinical terminologies, and these mappings between terminologies can help enrich gene annotation databases and unify phenotype representation. PMID- 20351827 TI - Development and evaluation of a study design typology for human research. AB - A systematic classification of study designs would be useful for researchers, systematic reviewers, readers, and research administrators, among others. As part of the Human Studies Database Project, we developed the Study Design Typology to standardize the classification of study designs in human research. We then performed a multiple observer masked evaluation of active research protocols in four institutions according to a standardized protocol. Thirty-five protocols were classified by three reviewers each into one of nine high-level study designs for interventional and observational research (e.g., N-of-1, Parallel Group, Case Crossover). Rater classification agreement was moderately high for the 35 protocols (Fleiss' kappa = 0.442) and higher still for the 23 quantitative studies (Fleiss' kappa = 0.463). We conclude that our typology shows initial promise for reliably distinguishing study design types for quantitative human research. PMID- 20351828 TI - A taxonomy characterizing complexity of consumer eHealth Literacy. AB - There are a range of barriers precluding patients from fully engaging in and benefiting from the spectrum of eHealth interventions developed to support patient access to health information, disease self-management efforts, and patient-provider communication. Consumers with low eHealth literacy skills often stand to gain the greatest benefit from the use of eHealth tools. eHealth skills are comprised of reading/writing/numeracy skills, health literacy, computer literacy, information literacy, media literacy, and scientific literacy [1]. We aim to develop an approach to characterize dimensions of complexity and to reveal knowledge and skill-related barriers to eHealth engagement. We use Bloom's Taxonomy to guide development of an eHealth literacy taxonomy that categorizes and describes each type of literacy by complexity level. Illustrative examples demonstrate the utility of the taxonomy in characterizing dimensions of complexity of eHealth skills used and associated with each step in completing an eHealth task. PMID- 20351829 TI - Measuring population health using personal health messages. AB - Personal health messages - inter patient communications within online communities; represent a new path towards providing continuous information about patient derived health status. We apply natural language processing techniques to personal health messages from online message boards to demonstrate the ability to track trends in people's positive or negative opinion (sentiment) regarding particular drugs over time. The significant changes in sentiment correspond to FDA announcements and other publicity. We envision such analysis as a scalable tool for pharmacovigilance hypothesis generation for possible adverse drug reactions. PMID- 20351830 TI - Laying the groundwork for enterprise-wide medical language processing services: architecture and process. AB - A systematic and standard process for capturing information within free-text clinical documents could facilitate opportunities for improving quality and safety of patient care, enhancing decision support, and advancing data warehousing across an enterprise setting. At Partners HealthCare System, the Medical Language Processing (MLP) services project was initiated to establish a component-based architectural model and processes to facilitate putting MLP functionality into production for enterprise consumption, promote sharing of components, and encourage reuse. Key objectives included exploring the use of an open-source framework called the Unstructured Information Management Architecture (UIMA) and leveraging existing MLP-related efforts, terminology, and document standards. This paper describes early experiences in defining the infrastructure and standards for extracting, encoding, and structuring clinical observations from a variety of clinical documents to serve enterprise-wide needs. PMID- 20351831 TI - Reliable real-time clinical monitoring using sensor network technology. AB - We propose wireless sensor networks composed of nodes using low-power 802.15.4 radios as an enabling technology for patient monitoring in general hospital wards. A key challenge for such applications is to reliably deliver sensor data from mobile patients. We propose a monitoring system with two types of nodes: patient nodes equipped with wireless pulse oximeters and relays nodes used to route data to a base station. A reliability analysis of data collection from mobile users shows that mobility leads to packet losses exceeding 30%. The majority of packet losses occur between the mobile subjects and the first-hop relays. Based on this insight we developed the Dynamic Relay Association Protocol (DRAP), an effective mechanism for discovering the right relays for patient nodes. DRAP enables highly reliable data collection from mobile subjects. Empirical evaluation showed that DRAP delivered at least 96% of data from multiple users. Our results demonstrate the feasibility of wireless sensor networks for real-time clinical monitoring. PMID- 20351832 TI - The contribution of observational studies and clinical context information for guiding the integration of infobuttons into clinical information systems. AB - The integration of information resources into clinical information systems may be based on a variety of approaches, including what is practical to provide, what is hypothetically useful, and (based on user studies) what is empirically useful. Resource selection may also be based on the user's context (role, task, patient demographics, concept of interest, etc.). METHODS: Two years of log files showing the context-specific use of information resources, especially via use of an infobutton manager (IM), were examined for patterns of usage. RESULTS: 3483 known unique users (and an unknown number of anonymous users) accessed information resources 65,128 times, including the use of the IM 21,907 times by at least 2367 unique users. Links provided in response to empirical information needs accounted for 16% of the total links and 32% of the accesses to information resources. Links that were provided based on patient demographics accounted for 29% of the total links and 13% of the accesses to information resources. Links that were provided based on the users concept of interest accounted for 21% of the total links and 13% of the accesses to information resources. CONCLUSION: Knowledge of observed information needs and of context attributes is useful for guiding automated selection of resource links by an Infobutton Manager. PMID- 20351833 TI - Predication-based semantic indexing: permutations as a means to encode predications in semantic space. AB - Corpus-derived distributional models of semantic distance between terms have proved useful in a number of applications. For both theoretical and practical reasons, it is desirable to extend these models to encode discrete concepts and the ways in which they are related to one another. In this paper, we present a novel vector space model that encodes semantic predications derived from MEDLINE by the SemRep system into a compact spatial representation. The associations captured by this method are of a different and complementary nature to those derived by traditional vector space models, and the encoding of predication types presents new possibilities for knowledge discovery and information retrieval. PMID- 20351834 TI - Temporal data mining for the assessment of the costs related to diabetes mellitus pharmacological treatment. AB - Diabetes care and chronic disease management represent data-intensive contexts which allow Local Healthcare Agencies (ASL) to collect a huge amount of information. Time is often an essential component of such information, given the strong importance of the temporal evolution of the considered disease and of its treatment. In this paper we show the application of a temporal data mining technique to extract temporal association rules over an integrated repository including both administrative and clinical data related to a sample of diabetic patients. We will show how the method can be used to highlight cases and conditions which lead to the highest pharmaceutical costs. Considering the perspective of a Regional Healthcare Agency, this method could be properly exploited to assess the overall standards and quality of care, while lowering costs. PMID- 20351835 TI - Using Bayesian networks and rule-based trending to predict patient status in the intensive care unit. AB - Multivariate Bayesian models trained with machine learning, in conjunction with rule-based time-series statistical techniques, are explored for the purpose of improving patient monitoring. Three vital sign data streams and known outcomes for 36 intensive care unit (ICU) patients were captured retrospectively and used to train a set of Bayesian net models and to construct time-series models. Models were validated on a reserved dataset from 16 additional patients. Receiver operating characteristic (ROC) curves were calculated. Area under the curve (AUC) was 91% for predicting improving outcome. The model's AUC for predicting declining outcome increased from 70% to 85% when the model was indexed to personalized baselines for each patient. The rule-based trending and alerting system was accurate 100% of the time in alerting a subsequent decline in condition. These techniques promise to improve the monitoring of ICU patients with high-sensitivity alerts, fewer false alarms, and earlier intervention. PMID- 20351836 TI - Video-mediated communication in hospice interdisciplinary team meetings: examining technical quality and content. AB - This study aims to determine how videoconferencing quality impacts the style and content of communication between members of hospice interdisciplinary teams and patients and their families. We videotaped video-calls between hospice teams and family caregivers based on the use of low-cost videophones. We assessed their audio and video quality using both a form that was filled out on site and a protocol for retrospective analysis. The tapes were transcribed and a content analysis was performed to assess the themes of interaction. A total of 70 video calls were analyzed. The time spent on general informal talk was significantly correlated to the video and audio quality of the session (r=0.43 and 0.41 respectively, p<0.001). The time spent addressing psychosocial issues and on caregiver education correlated significantly to video and audio quality. This study demonstrates the potential of video-mediated communication that supports shared decision making in hospice. PMID- 20351837 TI - Development of a natural language processing system to identify timing and status of colonoscopy testing in electronic medical records. AB - Colorectal cancer (CRC) screening rates are low despite proven benefits. We developed natural language processing (NLP) algorithms to identify temporal expressions and status indicators, such as "patient refused" or "test scheduled." The authors incorporated the algorithms into the KnowledgeMap Concept Identifier system in order to detect references to completed colonoscopies within electronic text. The modified NLP system was evaluated using 200 randomly selected electronic medical records (EMRs) from a primary care population aged >/=50 years. The system detected completed colonoscopies with recall and precision of 0.93 and 0.92. The system was superior to a query of colonoscopy billing codes to determine screening status. PMID- 20351838 TI - Development of an asthma management system in a pediatric emergency department. AB - Asthma is the leading chronic childhood disease with exacerbations resulting in urgent and emergency care visits. Guidelines adherence improves patient care but is suboptimal. A computerized guideline system can help improve compliance through automatic initiation and reminders to increase adherence. We designed a computerized management system for asthma care in the pediatric emergency department (ED). The system will be evaluated in two phases. The first phase evaluates a computerized diagnostic prompt using the ED's existing asthma protocol. The second phase evaluates a computerized asthma management system including temporal reminder elements for scoring and medication orders. The system was developed in conjunction with the pediatric ED multidisciplinary care team. The computerized system is entirely automatic and a prospective evaluation of the diagnostic component is ongoing. PMID- 20351839 TI - Enhancing the informatics evaluation toolkit with remote usability testing. AB - Developing functional clinical informatics products that are also usable remains a challenge. Despite evidence that usability testing should be incorporated into the lifecycle of health information technologies, rarely does this occur. Challenges include poor standards, a lack of knowledge around usability practices, and the expense involved in rigorous testing with a large number of users. Remote usability testing may be a solution for many of these challenges. Remotely testing an application can greatly enhance the number of users who can iteratively interact with a product, and it can reduce the costs associated with usability testing. A case study presents the experiences with remote usability testing when evaluating a Web site designed for health informatics knowledge dissemination. The lessons can inform others seeking to enhance their evaluation toolkits for clinical informatics products. PMID- 20351841 TI - Persistent paper: the myth of "going paperless". AB - How does paper usage change following the introduction of Computerized Physician Order Entry and the Electronic Medical Record (EMR/CPOE)? To answer that question we analyzed data collected from fourteen sites across the U.S. We found paper in widespread use in all institutions we studied. Analysis revealed psychological, ergonomic, technological, and regulatory reasons for the persistence of paper in an electronic environment. Paper has unique attributes allowing it to fill gaps in information timeliness, availability, and reliability in pursuit of improved patient care. Creative uses have led to "better paper." PMID- 20351840 TI - Fall TIPS: strategies to promote adoption and use of a fall prevention toolkit. AB - Patient falls are serious problems in hospitals. Risk factors for falls are well understood and nurses routinely assess for fall risk on all hospitalized patients. However, the link from nursing assessment of fall risk, to identification and communication of tailored interventions to prevent falls is yet to be established. The Fall TIPS (Tailoring Interventions for Patient Safety) Toolkit was developed to leverage existing practices and workflows and to employ information technology to improve fall prevention practices. The purpose of this paper is to describe the Fall TIPS Toolkit and to report on strategies used to drive adoption of the Toolkit in four acute care hospitals. Using the IHI "Framework for Spread" as a conceptual model, the research team describes the "spread" of the Fall TIPS Toolkit as means to integrate effective fall prevention practices into the workflow of interdisciplinary caregivers, patients and family members. PMID- 20351842 TI - Impact of precautionary behaviors during outbreaks of pandemic influenza: modeling of regional differences. AB - Using time geographic theory for representation of population mixing, we set out to analyze the relative impact from precautionary behaviors on outbreaks of pandemic influenza in Europe and Asia. We extended an existing simulator environment with behavioral parameters from a population survey to model different behaviors. We found that precautionary behaviors even among a minority of the population can have a decisive effect on the probability of the outbreak to propagate. The results also display that assumptions strongly influences the outcome. Depending on the interpretation of how many "children" are kept from "school", R(0) changes from a range where outbreak progression is possible to a range where it is improbable in both European (R(0)=1.77/1.23) and Asian (R(0)=1.70/1.05) conditions. We conclude that unprompted distancing can have a decisive effect on pandemic propagation. An important response strategy can be to promote voluntary precautionary behavior shown to reduce disease transmission. PMID- 20351843 TI - Clinician adoption of genetic testing for drug metabolizing enzymes: is patient safety the low-hanging fruit of personalized medicine? AB - With the advent of low cost genotyping, personalized medicine (PGx) has entered the clinical realm. PGx assesses inter-individual variability of drug metabolizing enzymes prior to drug therapy. Consequently, toxicity based adverse events stemming from patient metabolism may be avoided. This paper considers two applications: a genetic test of the CYP 2C9 enzyme prior to administration of the anticoagulant warfarin, and a test of the thiopurine methyltransferase gene prior to initiating therapy with mercaptopurine drugs. Clinician experience has been limited and the biomedical literature suggests that is due to barriers to PGx. These include a perceived lack of efficacy from an absence of prospective clinical trials, legacy pharmaceutical industry and physician business models, inadequate regulatory oversight, payer reimbursement practices, and physician habits. Until these are addressed, it is unlikely that PGx will achieve wide usage. Unproven utility and entrenched business models are the most significant impediments to clinician adoption. PMID- 20351844 TI - Assumptions management in simulation of infectious disease outbreaks. AB - Simulation of outbreaks of infectious disease is an important tool for understanding the dynamics of the outbreak process, the impact of disease and population properties, and the potential effect of interventions. However, the interpretation of the simulation results requires a clear understanding of the assumptions made in the underlying model. Typical simulation tasks, such as exploring the space of different scenarios for population and disease properties, require multiple runs with varying model parameters. For such complex tasks, the management of the assumptions made becomes a daunting and potentially error-prone undertaking. We report explicit assumptions management as an approach to capture, model, and document the assumptions for simulator runs. It was found possible to extend ontology-based simulation, which uses an ontological model to parameterize the simulator, to incorporate an assumptions model in the ontology. We conclude that explicit assumptions modeling should be part of any infectious disease simulation architecture from start. PMID- 20351845 TI - Computer surveillance of hospital-acquired infections: a 25 year update. AB - Hospital-acquired infections (HAIs) are a significant cause of patient harm and increased healthcare cost. Many states have instituted mandatory hospital-wide reporting of HAIs which will increase the workload of infection preventionists and the Center for Medicare and Medicaid Services is no longer paying hospitals to treat certain HAIs. These competing priorities for increased reporting and prevention have many hospitals worried. Manual surveillance of HAIs cannot provide the speed, accuracy and consistency of computerized surveillance. Computer tools can also improve the speed and accuracy of HAI analysis and reporting. Computerized surveillance for HAIs was implemented at LDS Hospital in 1984, but that system required manual entry of data for analysis and reporting. This paper reports on the current functionality and status of the updated computer system for HAI surveillance, analysis and reporting used at LDS Hospital and the 21 other Intermountain Healthcare hospitals. PMID- 20351846 TI - Generating quality word sense disambiguation test sets based on MeSH indexing. AB - Word sense disambiguation (WSD) determines the correct meaning of a word that has more than one meaning, and is a critical step in biomedical natural language processing, as interpretation of information in text can be correct only if the meanings of their component terms are correctly identified first. Quality evaluation sets are important to WSD because they can be used as representative samples for developing automatic programs and as referees for comparing different WSD programs. To help create quality test sets for WSD, we developed a MeSH-based automatic sense-tagging method that preferentially annotates terms being topical of the text. Preliminary results were promising and revealed important issues to be addressed in biomedical WSD research. We also suggest that, by cross validating with 2 or 3 annotators, the method should be able to efficiently generate quality WSD test sets. Online supplement is available at: http://www.dbmi.columbia.edu/~juf7002/AMIA09. PMID- 20351847 TI - Tailoring vocabularies for NLP in sub-domains: a method to detect unused word sense. AB - We developed a method to help tailor a comprehensive vocabulary system (e.g. the UMLS) for a sub-domain (e.g. clinical reports) in support of natural language processing (NLP). The method detects unused sense in a sub-domain by comparing the relational neighborhood of a word/term in the vocabulary with the semantic neighborhood of the word/term in the sub-domain. The semantic neighborhood of the word/term in the sub-domain is determined using latent semantic analysis (LSA). We trained and tested the unused sense detection on two clinical text corpora: one contains discharge summaries and the other outpatient visit notes. We were able to detect unused senses with precision from 79% to 87%, recall from 48% to 74%, and an area under receiver operation curve (AUC) of 72% to 87%. PMID- 20351848 TI - Comparing inconsistent relationship configurations indicating UMLS errors. AB - The goal of this paper is to audit null-annotated parent-child pairs in the UMLS Metathesaurus. We have developed techniques for identifying suspicious pairs with high likelihood of errors by using inconsistencies between the hierarchical relationships of the Metathesaurus and the Semantic Network. Two formal conditions, called semantic inversion and lack of ancestry are investigated. Analyzing two corresponding samples shows that semantic inversion is significantly more likely to indicate an error than lack of ancestry, which in turn is more likely to indicate errors than a consistent configuration. We also discuss cases of parent-child pairs with semantic inversion that may be corrected by disambiguating the child. PMID- 20351849 TI - Creating mappings for ontologies in biomedicine: simple methods work. AB - Creating mappings between concepts in different ontologies is a critical step in facilitating data integration. In recent years, researchers have developed many elaborate algorithms that use graph structure, background knowledge, machine learning and other techniques to generate mappings between ontologies. We compared the performance of these advanced algorithms on creating mappings for biomedical ontologies with the performance of a simple mapping algorithm that relies on lexical matching. Our evaluation has shown that (1) most of the advanced algorithms are either not publicly available or do not scale to the size of biomedical ontologies today, and (2) for many biomedical ontologies, simple lexical matching methods outperform most of the advanced algorithms in both precision and recall. Our results have practical implications for biomedical researchers who need to create alignments for their ontologies. PMID- 20351850 TI - Exploitation of speculation markers to identify the structure of biomedical scientific writing. AB - The motivation of this work is to study the use of speculation markers within scientific writing: this may be useful for discovering whether these markers are regularly spread across biomedical articles and then for establishing the logical structure of articles. To achieve these objectives, we compute associations between article sections and speculation markers. We use machine learning algorithms to show that there are strong and interesting associations between speculation markers and article structure. For instance, strong markers, which strongly influence the presentation of knowledge, are specific to Results, Discussion and Abstract; while non strong markers appear with higher regularity within Material and Methods. Our results indicate that speculation is governed by observable usage rules within scientific articles and can help their structuring. PMID- 20351851 TI - Care coordination and electronic health records: connecting clinicians. AB - OBJECTIVE: To examine the association between use of electronic health records (EHR) and care coordination. STUDY DESIGN: Two surveys, in 2005 and again in 2006, of primary care clinicians working in a prepaid integrated delivery system during the staggered implementation of an EHR system. Using multivariate logistic regression to adjust for clinician characteristics, we examined the association between EHR use and clinicians' perceptions of three dimensions of care coordination: timely access to complete information; treatment goal agreement; and role/responsibility agreement. RESULTS: Compared to clinicians without EHR, clinicians with 6+ months of EHR use more frequently reported timely access to complete information, and being in agreement on treatment goals with other involved clinicians. There was no significant association between EHR use and being in agreement on roles and responsibilities with other clinicians. CONCLUSIONS: EHR use is associated with aspects of care coordination involving information transfer and communication of treatment goals. PMID- 20351852 TI - Social network analyses of patient-healthcare worker interactions: implications for disease transmission. AB - Patients and healthcare workers (HCW) in healthcare settings represent a unique social network in which the risk of transmission of an infection is considered to be higher for both HCW and patients. Using data from existing clinical informatics resources, we constructed social networks of patient-HCW interactions in the emergency department of a tertiary care pediatric hospital. The structural properties of these networks were analyzed and compared to other well known networks. Patient-HCW networks do not demonstrate the classical power-law distribution of scale-free networks, thus indicating that they are different from social networks of individuals in a community. The clustering coefficient is larger as compared to a random network, indicating small world properties. The eigenvector centrality, used to identify the most important nodes, reveals HCW to be more connected than patients. These properties imply differences that must be taken into account when analyzing patient-HCW networks and planning interventions and mitigation strategies to prevent the spread of infectious diseases in healthcare settings. PMID- 20351853 TI - Use of clinical alerting to improve the collection of clinical research data. AB - Data errors in electronic health records have been shown to have the potential to adversely impact the conclusions drawn from clinical research. We prospectively studied the efficacy of a new alert to infer errors in previously stored data and to decrease the frequency of data entry errors, in an attempt to improve the quality of data for clinical trials. For the purpose of this study, we monitored data entry errors in height or weight measurements. We predetermined the criteria for probable error as a ten percent variance from a patient's reference value. The care provider entering a value satisfying our error criteria received a disruptive pop-up alert message. The study revealed a significant decrease in the frequency of data errors stored in the EHR, from 2.4% before the alert to 0.9% after the alert. These findings have implications for the development of clinical research trial data collection support tools. PMID- 20351854 TI - Examining the relationship between clinical decision support and performance measurement. AB - In concept and practice, clinical decision support (CDS) and performance measurement represent distinct approaches to organizational change, yet these two organizational processes are interrelated. We set out to better understand how the relationship between the two is perceived, as well as how they jointly influence clinical practice. To understand the use of CDS at benchmark institutions, we conducted semistructured interviews with key managers, information technology personnel, and clinical leaders during a qualitative field study. Improved performance was frequently cited as a rationale for the use of clinical reminders. Pay-for-performance efforts also appeared to provide motivation for the use of clinical reminders. Shared performance measures were associated with shared clinical reminders. The close link between clinical reminders and performance measurement causes these tools to have many of the same implementation challenges. PMID- 20351855 TI - Automating quality measurement: a system for scalable, comprehensive, and routine care quality assessment. AB - Electronic medical records (EMRs) hold the promise of making routine comprehensive measurement of care quality a reality. However, there are many informatics challenges that stand in the way of this goal. Guidelines are rarely stated in precise enough language for automated measurement of clinical practices and the data necessary for that measurement often reside in the text notes of EMRs. We designed a technology platform for scalable and routine measurement of care quality using comprehensive EMR data, including providers' freetext notes documenting clinical encounters. We are in the process of implementing this system to assess the quality of ambulatory asthma care in two diverse healthcare systems: a mid-size HMO and a consortium of Federally Qualified Healthcare Center (FQHC) clinics on the west coast of the United States. PMID- 20351856 TI - Collaborative authoring of biomedical terminologies using a semantic Wiki. AB - To be broadly useful, biomedical terminologies need to capture the knowledge and expertise of multiple experts, research groups and end users. Consequently, the construction of such a terminology requires collaboration among multiple participants. This paper summarizes several terminology projects which employ a collaborative authoring mode in development, along with the various tools used by these projects to support collaboration, such as mailing list, issue tracking system, client-side GUI software and Wiki system. We then discuss the essential functional requirements for a collaborative authoring tool in the context of terminology development, and analyze the inherent features of Semantic Wiki that enable it to be a competent tool used in this type of effort. To demonstrate, we describe a prototype system of collaborative authoring for health care terminologies built upon the Semantic Wiki technology. Finally, we discuss the potential issues that might be associated with this open Semantic Wiki platform. PMID- 20351857 TI - Evaluation of LOINC for representing constitutional cytogenetic test result reports. AB - Genetic testing is becoming increasingly important to medical practice. Integrating genetics and genomics data into electronic medical records is crucial in translating genetic discoveries into improved patient care. Information technology, especially Clinical Decision Support Systems, holds great potential to help clinical professionals take full advantage of genomic advances in their daily medical practice. However, issues relating to standard terminology and information models for exchanging genetic testing results remain relatively unexplored. This study evaluates whether the current LOINC standard is adequate to represent constitutional cytogenetic test result reports using sample result reports from ARUP Laboratories. The results demonstrate that current standard terminology is insufficient to support the needs of coding cytogenetic test results. The terminology infrastructure must be developed before clinical information systems will be able to handle the high volumes of genetic data expected in the near future. PMID- 20351858 TI - Automated mapping of pharmacy orders from two electronic health record systems to RxNorm within the STRIDE clinical data warehouse. AB - The Stanford Translational Research Integrated Database Environment (STRIDE) clinical data warehouse integrates medication information from two Stanford hospitals that use different drug representation systems. To merge this pharmacy data into a single, standards-based model supporting research we developed an algorithm to map HL7 pharmacy orders to RxNorm concepts. A formal evaluation of this algorithm on 1.5 million pharmacy orders showed that the system could accurately assign pharmacy orders in over 96% of cases. This paper describes the algorithm and discusses some of the causes of failures in mapping to RxNorm. PMID- 20351859 TI - The human factor in medical emergency simulation. AB - Medical errors rank high amongst leading causes of death. Especially in emergency care, when there is limited time to think, the "human factor", the interface between human action and the environmental system, has been recognized to be a critical part that determines the outcome. Recent models of human error are based on the principle that critical incidents are of multifactorial origin and reflect insufficiencies of the underlying system itself. The Human Simulation Center (HSC) was built specifically to train interaction between medical teams and to investigate the human factor in medical emergencies. In the following article we present "MevidIO", a live-monitoring and debriefing application framework. Developed for a full-scale simulation center designed to model error transduction in medical emergency care process chains, the framework integrates educational and scientific aspects. PMID- 20351860 TI - Semantic relations for interpreting DNA microarray data. AB - The results from microarray experiments, in the form of lists of over- and under expressed genes, have great potential to support progress in biomedical research. However, results are not easy to interpret. Information about the function of the genes and their relation to other genes is needed, and this information is usually present in vast amounts of biomedical literature. Considerable effort is required to find, read and extract relevant information from the literature. A potential solution is to use computerized text analysis methods to extract relevant information. Our proposal enhances current methods in this regard and uses semantic relations extracted from biomedical text with the SemRep information extraction system. We describe an application that integrates microarray results with semantic relations and discuss its benefits in supporting enhanced access to the relevant literature for interpretation of results. PMID- 20351861 TI - ICU acuity: real-time models versus daily models. AB - OBJECTIVE: To explore the feasibility of real-time mortality risk assessment for ICU patients. DESIGN/METHODS: This study used retrospective analysis of mixed medical/surgical intensive care patients in a university hospital. Logistic regression was applied to 7048 development patients with several hundred candidate variables. Final models were selected by backward elimination on top cross-validated variables and validated on 3018 separate patients. RESULTS: The real-time model demonstrated strong discrimination ability (Day 3 AUC=0.878). All models had circumstances where calibration was poor (Hosmer-Lemeshow goodness of fit test p < 0.1). The final models included variables known to be associated with mortality, but also more computationally intensive variables absent in other severity scores. CONCLUSION: Real-time mortality prediction offers similar discrimination ability to daily models. Moreover, the discrimination of our real time model performed favorably to a customized SAPS II (Day 3 AUC=0.878 vs AUC=0.849, p < 0.05) but generally had worse calibration. PMID- 20351862 TI - Tracking medication information across medical records. AB - A patient's electronic medical record can consist of a large number of reports, especially for an elderly patient or for one affected by a chronic disease. It can thus be cumbersome for a physician to go through all of the reports to understand the patient's complete medical history. This paper describes work in progress towards tracking medications and their dosages through the course of a patient's medical history. 923 reports associated with 11 patients were obtained from a university hospital. Drug names were identified using a dictionary look-up approach. Dosages corresponding to these drugs were determined using regular expressions. The state of a drug (ON, OFF), which determines whether or not the drug was being taken, was identified using a support vector machine with features based on expert knowledge. Results were promising: prec. approximately recall approximately 87%. The output is a timeline display of the drugs which the patient has been taking. PMID- 20351863 TI - Methodology to develop and evaluate a semantic representation for NLP. AB - Natural language processing applications that extract information from text rely on semantic representations. The objective of this paper is to describe a methodology for creating a semantic representation for information that will be automatically extracted from textual clinical records. We illustrate two of the four steps of the methodology in this paper using the case study of encoding information from dictated dental exams: (1) develop an initial representation from a set of training documents and (2) iteratively evaluate and evolve the representation while developing annotation guidelines. Our approach for developing and evaluating a semantic representation is based on standard principles and approaches that are not dependent on any particular domain or type of semantic representation. PMID- 20351864 TI - A Bayesian network model for analysis of detection performance in surveillance systems. AB - Worldwide developments concerning infectious diseases and bioterrorism are driving forces for improving aberrancy detection in public health surveillance. The performance of an aberrancy detection algorithm can be measured in terms of sensitivity, specificity and timeliness. However, these metrics are probabilistically dependent variables and there is always a trade-off between them. This situation raises the question of how to quantify this tradeoff. The answer to this question depends on the characteristics of the specific disease under surveillance, the characteristics of data used for surveillance, and the algorithmic properties of detection methods. In practice, the evidence describing the relative performance of different algorithms remains fragmented and mainly qualitative. In this paper, we consider the development and evaluation of a Bayesian network framework for analysis of performance measures of aberrancy detection algorithms. This framework enables principled comparison of algorithms and identification of suitable algorithms for use in specific public health surveillance settings. PMID- 20351865 TI - Generalized AMOC curves for evaluation and improvement of event surveillance. AB - We introduce Generalized Activity Monitoring Operating Characteristic (G-AMOC) curves, a new framework for evaluation of outbreak detection systems. G-AMOC curves provide a new approach to evaluating and improving the timeliness of disease outbreak detection by taking the user's response protocol into account and considering when the user will initiate an investigation in response to the system's alerts. The standard AMOC curve is a special case of G-AMOC curves that assumes a trivial response protocol (initiating a new and separate investigation in response to each alert signal). Practical application of a surveillance system is often improved, however, by using more elaborate response protocols, such as grouping alerts or ignoring isolated signals. We present results of experiments demonstrating that we can use G-AMOC curves as 1) a descriptive tool, to provide a more accurate comparison of systems than the standard AMOC curve, and 2) as a prescriptive tool, to choose appropriate response protocols for a detection system, and thus improve its performance. PMID- 20351866 TI - Evaluation of risk scores derived from the health family tree program. AB - Family health history is an independent risk factor for certain diseases. The Health Family Tree (HFT) was developed and used to document and assess family health history from the families of high school students since 1980. While the risk algorithm of the HFT was initially validated, 20 years of use as a public health tool in the community provides an extremely large dataset for more rigorous validation. A retrospective cohort study was used with the events before the "cut-off" year as the baseline and the events after the "cut-off" year as the follow-up. Baseline data were used in the algorithm to calculate the Family History Score (FHS). Cox proportional hazards model was used to test the dose response nature of the FHS for predicting incident events. An FHS >/=1 was determined to be a significant predictor for future development of diabetes, myocardial infarction, and early onset of myocardial infarction. PMID- 20351867 TI - Assisting the translation of SNOMED CT into French using UMLS and four representative French-language terminologies. AB - OBJECTIVE: To provide a semantics-based method to assist the translation of SNOMED CT into French. To do so, we selected four French-language terminologies: ICD-10, SNOMED International, MedDRA, MeSH, as they are dedicated to different uses - epidemiology, clinical medicine, adverse reactions, medical literature, respectively - in order to map them to SNOMED Clinical Terms (CT), and thus associate French terms with SNOMED CT concepts. In this way, we measured the number of SNOMED CT concepts to be found in French-language terminologies. MATERIAL AND METHOD: We used the UMLS Metathesaurus. The mapping method was based on the coincidence of identifiers and on the explicit mappings present in the Metathesaurus. RESULTS: The study dealt exclusively with preferred terms (PTs) in the terminologies. The terminologies are mapped with varying success as regards PTs mapped to SNOMED terms (from 52% to 96%). Conversely, 45% of SNOMED CT terms are mapped by uniting the four terminologies. DISCUSSION: A more effective mapping technique than the current method is under consideration. CONCLUSION: The method presented will be refined. It could certainly provide useful assistance in the translation of SNOMED CT into French. Due to its general nature, it could be used to translate SNOMED CT into other languages than French. PMID- 20351868 TI - Is Web-only self-care education sufficient for heart failure patients? AB - Heart failure patients require complex, long-term care. Research shows that self care education improves health outcomes of these patients. This study reports the results of a randomized trial which compared the effects of two remote educational interventions on heart failure patients' knowledge of self-care practices. The first group reviewed self-care content on a Web site and had email access to a cardiac nurse. The second group had access to the Web site, and participated in four telephone-based sessions with the cardiac nurse. The test scores of both groups significantly improved following the intervention. However, the post-intervention test scores of the group that included telephone sessions were significantly higher than the scores for the group that had access to the Web site only. These results show a benefit to learning of a teleconferencing intervention that is over and above the benefit of an intervention based on Web information and email access alone. PMID- 20351869 TI - A systematic approach to using case studies in health informatics education. AB - The complexity of health informatics (HI) projects necessitates a solid base of skills and knowledge in a variety of different fields. Case studies are an excellent way to introduce this complexity without overwhelming students. This paper makes a contribution to HI education by presenting a systematic approach to introducing HI concepts to future health informatics professionals (HIPs) and to health care professionals and administrators who need a solid grounding to participate in HI projects. PMID- 20351870 TI - Evaluation of the PharmGKB knowledge base as a resource for efficiently assessing the clinical validity and utility of pharmacogenetic assays. AB - Prior to clinical use, pharmacogenetic tests should be systematically evaluated for their clinical validity and utility. Here, we evaluated whether the publicly available, online Pharmacogenomics Knowledge Base (PharmGKB) could facilitate such assessments by efficiently identifying relevant peer-reviewed manuscripts. The search targets were 55 manuscripts regarding clinical validity and utility included in systematic reviews of warfarin, antidepressant, and irinotecan pharmacogenetics. When direct inclusion in PharmGKB was the search criterion, recall was 33% and precision was 16%. However, recall increased to 78% when citation within a PharmGKB-identified manuscript was added as a search criterion. These recalled manuscripts accounted for 87% of the study subjects, and domain experts determined that the omission of the remaining manuscripts was unlikely to have changed the conclusions of the reviews. Thus, we conclude that PharmGKB can facilitate the systematic assessment of pharmacogenetic assays through the efficient identification of relevant peer-reviewed manuscripts. PMID- 20351871 TI - Profile-based retrieval of records in medical databases. AB - Ontologies establish relationships between different terms, yet their potential in querying has not yet been fully realized. In this paper, we study the problem of ontology-supported profile-based retrieval of medical records. We present an algorithm that provides two independent techniques (used in isolation or in unison) to address the shortcomings of existing keyword-based retrieval solutions, and provide an implementation and experiments to illustrate the merits of our approach. PMID- 20351872 TI - GetHealthyHarlem.org: developing a web platform for health promotion and wellness driven by and for the Harlem community. AB - GetHealthyHarlem.org is a community website developed on an open-source platform to facilitate collaborative development of health content through participatory action research (PAR) principles. The website was developed to enable the Harlem community to create a shared health and wellness knowledgebase, to enable discourse about local and culturally relevant health information, and to foster social connections between community members and health promotion organizations. The site is gaining active use with more than 9,500 unique site visits in the six months since going live in November, 2008. In ongoing research studies, we are using the website to explore how the PAR model can be applied to the development of a community health website. PMID- 20351874 TI - Hierarchical image classification in the bioscience literature. AB - Our previous work has shown that images appearing in bioscience articles can be classified into five types: Gel-Image, Image-of-Thing, Graph, Model, and Mix. For this paper, we explored and analyzed features strongly associated with each image type and developed a hierarchical image classification approach for classifying an image into one of the five types. First, we applied texture features to separate images into two groups: 1) a texture group comprising Gel Image, Image of-Thing, and Mix, and 2) a non-texture group comprising Graph and Model. We then applied entropy, skewness, and uniformity for the first group, and edge difference, uniformity, and smoothness for the second group to classify images into specific types. Our results show that hierarchical image classification accurately divided images into the two groups during the initial classification and that the overall accuracy of the image classification was higher than that of our previous approach. In particular, the recall of hierarchical image classification was greatly improved due to the high accuracy of the initial classification. PMID- 20351873 TI - Improving healthy behaviors in type 1 diabetic patients by interactive frameworks. AB - Patient empowerment is considered to be one of the key factors in improving and maintaining a patient's health status. Patient empowerment in chronic illnesses involves educating the patient after the initial diagnosis and then keeping the patient motivated to adhere to the treatment in the follow up period. The aim of this research is creating an interactive framework to improve adherence to treatment in type 1 diabetic (T1D) patients based on an existing theoretical behavioral change model. The proposed framework learns from the patient's situation based on the patient's adherence to treatment and the patient's personal profile; and then the framework adapts itself to the new situation and creates new strategies to motivate the patient in order to reinforce positive behavior on the part of the patient. Thus, the embedded self-care interactive framework empowers T1D patients in achieving improved health outcomes by adhering to long term treatments. PMID- 20351875 TI - A recommendation algorithm for automating corollary order generation. AB - Manual development and maintenance of decision support content is time-consuming and expensive. We explore recommendation algorithms, e-commerce data-mining tools that use collective order history to suggest purchases, to assist with this. In particular, previous work shows corollary order suggestions are amenable to automated data-mining techniques. Here, an item-based collaborative filtering algorithm augmented with association rule interestingness measures mined suggestions from 866,445 orders made in an inpatient hospital in 2007, generating 584 potential corollary orders. Our expert physician panel evaluated the top 92 and agreed 75.3% were clinically meaningful. Also, at least one felt 47.9% would be directly relevant in guideline development. This automated generation of a rough-cut of corollary orders confirms prior indications about automated tools in building decision support content. It is an important step toward computerized augmentation to decision support development, which could increase development efficiency and content quality while automatically capturing local standards. PMID- 20351876 TI - Using mobile & personal sensing technologies to support health behavior change in everyday life: lessons learned. AB - Lifestyle modification is a key facet of the prevention and management of chronic diseases. Mobile devices that people already carry provide a promising platform for facilitating these lifestyle changes. This paper describes key lessons learned from the development and evaluation of two mobile systems for encouraging physical activity. We argue that by supporting persistent cognitive activation of health goals, encouraging an extensive range of relevant healthy behaviors, focusing on long-term patterns of activity, and facilitating social support as an optional but not primary motivator, systems can be developed that effectively motivate behavior change and provide support when and where people make decisions that affect their health. PMID- 20351877 TI - An evidence-based decision aid to help patients set priorities for selecting among multiple health behaviors. AB - To explore how patients and providers respond to Tailored Lifestyle Conversations (TLC), an evidence-based decision aid to help patients set priorities for selecting among multiple health behavior change goals, we conducted a study utilizing key informant interviews. Based on patient level assessment data, TLC presents tailored outputs that include 1) behavioral and clinical risk; 2) readiness and confidence scores for changing each of four behaviors; and 3) qualitative equations to elicit patient priorities for change. Patient priorities are documented in an action plan to be discussed with their provider during a clinical encounter. Interview questions probed how patients and providers responded to this output, and how heavily they valued the chance of success versus health benefit in deciding which behavior to work on first. The interviews also revealed how TLC might mediate the conversation around behavior change between patients and providers. TLC has potential to drive a more evidence based and patient centric approach to behavioral counseling in clinical settings. PMID- 20351878 TI - Extracting cancer quality indicators from electronic medical records: evaluation of an ontology-based virtual medical record approach. AB - Measuring quality in clinical care is a time-consuming manual task. The vast amounts of clinical data collected through electronic medical records (EMRs) create an opportunity to develop tools that automatically assess quality indicators; however, the diversity of EMR implementations limits the ability to implement general, reusable methods. We evaluate an ontology-based virtual medical record (VMR) approach as a standardized, sharable methodology for defining data abstractions needed for quality of care assessment. Using a set of cancer quality indicators, we conducted a requirements analysis for modeling these abstractions with an OWL-based VMR. We found that the VMR approach needs to be extended to support population-based aggregations of clinical events, models of intended versus completed actions, and models of workflow and delivery systems. Incorporating the patient perspective on quality also requires additional extension of the VMR. We are using these results to create a virtual quality record based on EMR data. PMID- 20351879 TI - Persuading consumers to form precise search engine queries. AB - Today's search engines provide a single textbox for searching. This input method has not changed in decades and, as a result, consumer search behaviour has not changed either: few and imprecise keywords are used. Especially with health information, where incorrect information may lead to unwise decisions, it would be beneficial if consumers could search more precisely. We evaluated a new user interface that supports more precise searching by using query diagrams. In a controlled user study, using paper-based prototypes, we compared searching with a Google interface with drawing new or modifying template diagrams. We evaluated consumer willingness and ability to use diagrams and the impact on query formulation. Users had no trouble understanding the new search method. Moreover, they used more keywords and relationships between keywords with search diagrams. In comparison to drawing their own diagrams, modifying existing templates led to more searches being conducted and higher creativity in searching. PMID- 20351880 TI - Semantic reasoning with image annotations for tumor assessment. AB - Identifying, tracking and reasoning about tumor lesions is a central task in cancer research and clinical practice that could potentially be automated. However, information about tumor lesions in imaging studies is not easily accessed by machines for automated reasoning. The Annotation and Image Markup (AIM) information model recently developed for the cancer Biomedical Informatics Grid provides a method for encoding the semantic information related to imaging findings, enabling their storage and transfer. However, it is currently not possible to apply automated reasoning methods to image information encoded in AIM. We have developed a methodology and a suite of tools for transforming AIM image annotations into OWL, and an ontology for reasoning with the resulting image annotations for tumor lesion assessment. Our methods enable automated inference of semantic information about cancer lesions in images. PMID- 20351881 TI - TLC: an informatics approach to enable patients to initiate tailored lifestyle conversations with providers at the point of care. AB - Chronic illness including cardiovascular disease (CVD) is a major burden on the healthcare system. Behavioral and lifestyle changes could significantly reduce the burden of CVD, but provider counseling for behavior change is a very challenging, and often ineffective task. We have developed a patient-centric decision support tool to be incorporated into an Electronic Health Record system (EHR). The tool provides tailored feedback on behavioral risk, readiness and confidence in an effort to empower patients to make decisions about improving health behaviors. In turn, the tool will facilitate an informed and balanced discussion between patients and their providers about behavioral changes, incorporating both the clinical view and the individual's preferences for choosing among multiple behavior change goals based on their psychosocial characteristics, and evaluation of benefits and barriers. PMID- 20351882 TI - Toward a fully de-identified biomedical information warehouse. AB - The Information Warehouse at the Ohio State University Medical Center is a comprehensive repository of business, clinical, and research data from various source systems. Data collected here is a valuable resource that facilitates both translational research and personalized healthcare. The use of such data in research is governed by federal privacy regulations with oversight by the Institutional Review Board. In 2006, the Information Warehouse was recognized by the OSU IRB as an "Honest Broker" of clinical data, providing investigators with de-identified or limited datasets under stipulations contained in a signed data use agreement. In order to streamline this process even further, the Information Warehouse is developing a de-identified data warehouse that is suitable for direct user access through a controlled query tool that is aimed to support both research and education activities. In this paper we report our findings on performance evaluation of different de-identification schemes that may be used to ensure regulatory compliance while also facilitating practical database updating and querying. We also discuss how date-shifting in the de-identification process can impact other data elements such as diagnosis and procedure codes and consider a possible solution to those problems. PMID- 20351883 TI - iSMART: Ontology-based Semantic query of CDA documents. AB - The Health Level 7 Clinical Document Architecture (CDA) is widely accepted as the format for electronic clinical document. With the rich ontological references in CDA documents, the ontology-based semantic query could be performed to retrieve CDA documents. In this paper, we present iSMART (interactive Semantic MedicAl Record reTrieval), a prototype system designed for ontology-based semantic query of CDA documents. The clinical information in CDA documents will be extracted into RDF triples by a declarative XML to RDF transformer. An ontology reasoner is developed to infer additional information by combining the background knowledge from SNOMED CT ontology. Then an RDF query engine is leveraged to enable the semantic queries. This system has been evaluated using the real clinical documents collected from a large hospital in southern China. PMID- 20351884 TI - Facilitating consumer clinical information seeking by maintaining referential context: evaluation of a prototypic approach. AB - Millions of consumers seek health information on the Internet. Unfortunately, this searching often falls short because of design limitations of many consumer oriented Web sites. In this paper, we describe an approach that addresses several known barriers to consumer health information seeking. This approach primarily involves maintaining the referential context throughout a consumer's search for information. To maintain referential context, this approach uses multiple levels of hierarchical constructs to organize complex information, and data elements are toggled to minimize the need for scrolling. An information resource based on this approach was implemented for information about smoking using standard Web technologies. The resource was evaluated by 31 diverse consumers through standardized usability instruments. Consumers found the resource to be easy to navigate and to use. We conclude that the approach described in this manuscript could be applied more broadly to facilitate the organization and presentation of consumer health information. PMID- 20351885 TI - Using a statistical natural language Parser augmented with the UMLS specialist lexicon to assign SNOMED CT codes to anatomic sites and pathologic diagnoses in full text pathology reports. AB - To address the problem of extracting structured information from pathology reports for research purposes in the STRIDE Clinical Data Warehouse, we adapted the ChartIndex Medical Language Processing system to automatically identify and map anatomic and diagnostic noun phrases found in full-text pathology reports to SNOMED CT concept descriptors. An evaluation of the system's performance showed a positive predictive value for anatomic concepts of 92.3% and positive predictive value for diagnostic concepts of 84.4%. The experiment also suggested strategies for improving ChartIndex's performance coding pathology reports. PMID- 20351886 TI - STRIDE--An integrated standards-based translational research informatics platform. AB - STRIDE (Stanford Translational Research Integrated Database Environment) is a research and development project at Stanford University to create a standards based informatics platform supporting clinical and translational research. STRIDE consists of three integrated components: a clinical data warehouse, based on the HL7 Reference Information Model (RIM), containing clinical information on over 1.3 million pediatric and adult patients cared for at Stanford University Medical Center since 1995; an application development framework for building research data management applications on the STRIDE platform and a biospecimen data management system. STRIDE's semantic model uses standardized terminologies, such as SNOMED, RxNorm, ICD and CPT, to represent important biomedical concepts and their relationships. The system is in daily use at Stanford and is an important component of Stanford University's CTSA (Clinical and Translational Science Award) Informatics Program. PMID- 20351887 TI - Finding query suggestions for PubMed. AB - It is common for PubMed users to repeatedly modify their queries (search terms) before retrieving documents relevant to their information needs. To assist users in reformulating their queries, we report the implementation and usage analysis of a new component in PubMed called Related Queries, which automatically produces query suggestions in response to the original user's input. The proposed method is based on query log analysis and focuses on finding popular queries that contain the initial user search term with a goal of helping users describe their information needs in a more precise manner. This work has been integrated into PubMed since January 2009. Automatic assessment using clickthrough data show that each day, the new feature is used consistently between 6% and 10% of the time when it is shown, suggesting that it has quickly become a popular new feature in PubMed. PMID- 20351888 TI - Automatic home nursing activity recommendation. AB - The rapid deployment of Web-based, consumer-centric electronic medical records (CEMRs) is an important trend in healthcare. In this paper, we incorporate nursing knowledge into CEMR so that it can automatically recommend home nursing activities (HNAs). Those more complex HNAs are made clickable for users to find detailed implementation procedures. We demonstrate the effectiveness of our techniques using USMLE medical exam cases. PMID- 20351889 TI - Measuring stability of feature selection in biomedical datasets. AB - An important step in the analysis of high-dimensional biomedical data is feature selection. Typically, a feature subset selected by a feature selection method is evaluated for relevance towards a task such as prediction or classification. Another important property of a feature selection method is stability that refers to robustness of the selected features to perturbations in the data. In biomarker discovery, for example, domain experts prefer a parsimonious subset of features that are relatively robust to slight changes in the data. We present a stability measure called the adjusted stability measure that computes robustness of a feature selection method with respect to random feature selection. This measure is useful for comparing the robustness of feature selection methods and is superior to similar measures that do not account for random feature selection. We demonstrate the application of this measure on a biomedical dataset. PMID- 20351890 TI - Detection of blood culture bacterial contamination using natural language processing. AB - Microbiology results are reported in semi-structured formats and have a high content of useful patient information. We developed and validated a hybrid regular expression and natural language processing solution for processing blood culture microbiology reports. Multi-center Veterans Affairs training and testing data sets were randomly extracted and manually reviewed to determine the culture and sensitivity as well as contamination results. The tool was iteratively developed for both outcomes using a training dataset, and then evaluated on the test dataset to determine antibiotic susceptibility data extraction and contamination detection performance. Our algorithm had a sensitivity of 84.8% and a positive predictive value of 96.0% for mapping the antibiotics and bacteria with appropriate sensitivity findings in the test data. The bacterial contamination detection algorithm had a sensitivity of 83.3% and a positive predictive value of 81.8%. PMID- 20351891 TI - Inductive creation of an annotation schema and a reference standard for de identification of VA electronic clinical notes. AB - Accessing both structured and unstructured clinical data is a high priority for research efforts. However, HIPAA requires that data meet or exceed a deidentification standard to assure that protected health information (PHI) is removed. This is a particularly difficult problem in the case of unstructured clinical free text and natural language processing (NLP) systems can be trained to automatically de-identify clinical text. Moreover, manual human annotation of clinical note documents for the purpose of building reference standards to evaluate NLP systems is a costly and time consuming process. Annotation schema must be created that can be used to build reliable and valid reference standards to evaluate NLP systems for the deidentification task. We describe the inductive creation of an annotation schema and subsequent reference standard. We also provide estimates of the accuracy of human annotators for this particular task. PMID- 20351892 TI - Duplicate medical records: a survey of Twin Cities healthcare organizations. AB - Duplicate medical records occur when a single patient is associated with more than one medical record number. This causes a dangerous and expensive issue for hospitals and health information technology. A survey was constructed to gather qualitative information from Twin Cities healthcare organizations. The goal was to determine baseline information regarding the recognition of the problems surrounding duplicate medical record creation and organizational strategies for resolutions. The survey demonstrated that all organizations acknowledged the importance and patient safety issue regarding the creation of duplicates but the strategies and solutions are varied. As defined in the Minnesota Alliance for Patient Safety5, the ultimate goal of this survey was to favorably impact patient safety. The deidentified results were disseminated to all participating organizations along with recommendations for system improvements in order to raise awareness of the issue and promote patient safety. PMID- 20351893 TI - Perplexity analysis of obesity news coverage. AB - An important task performed during the analysis of health news coverage is the identification of news articles that are related to a specific health topic (e.g. obesity). This is often done using a combination of keyword searching and manual encoding of news content. Statistical language models and their evaluation metric, perplexity, may help to automate this task. A perplexity study of obesity news was performed to evaluate perplexity as a measure of the similarity of news corpora to obesity news content. The results of this study showed that perplexity increased as news coverage became more general relative to obesity news (obesity news approximately 187, general health news approximately 278, general news approximately 378, general news across multiple publishers approximately 382). This indicates that language model perplexity can measure the similarity news content to obesity news coverage, and could be used as the basis for an automated health news classifier. PMID- 20351894 TI - UMLS-Interface and UMLS-Similarity : open source software for measuring paths and semantic similarity. AB - A number of computational measures for determining semantic similarity between pairs of biomedical concepts have been developed using various standards and programming platforms. In this paper, we introduce two new open-source frameworks based on the Unified Medical Language System (UMLS). These frameworks consist of the UMLS-Similarity and UMLS-Interface packages. UMLS-Interface provides path information about UMLS concepts. UMLS-Similarity calculates the semantic similarity between UMLS concepts using several previously developed measures and can be extended to include new measures. We validate the functionality of these frameworks by reproducing the results from previous work. Our frameworks constitute a significant contribution to the field of biomedical Natural Language Processing by providing a common development and testing platform for semantic similarity measures based on the UMLS. PMID- 20351895 TI - Taxonomy development and knowledge representation of nurses' personal cognitive artifacts. AB - Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive artifacts of other disciplines. Understanding the development and purpose of practitioner's knowledge representations provides important direction to informaticists seeking to create information technology alternatives. The outcome of this paper is to suggest a process template for transition of cognitive artifacts to an information system. PMID- 20351896 TI - A clinical use case to evaluate the i2b2 Hive: predicting asthma exacerbations. AB - To evaluate the i2b2 Hive as a tool to query, visualize, and extract clinical data, we selected a use case from the i2b2 airways diseases driving biology project: asthma exacerbations prediction. We analyzed the cohort selection and the extraction of the clinical data used by this asthma exacerbations prediction study. The structured data included the asthma diagnosis, birthdate, age, race, sex, height, weight, and BMI. The smoking status is typically only mentioned in clinical notes, and we evaluated the Natural Language Processing (NLP) application embedded in the i2b2 NLP cell to extract the smoking status from history and physical exam reports.Querying structured data was possible with the i2b2 workbench for about half the clinical data elements. The remaining had to be queried using a commercial database management system client. The automated extraction of the smoking status reached a mean precision of 0.79 and a mean specificity of 0.90. PMID- 20351897 TI - Using a pipeline to improve de-identification performance. AB - Effective de-identification methods are needed to support reuse of electronic health record data for research and other purposes. We investigated using two different text-processing systems in tandem as a strategy for de-identification of clinical notes. We ran 100 outpatient notes through deid.pl, from MIT's PhysioToolkit, followed by MedLEE, and we manually compared the output with original notes to determine the amount of protected health information (PHI) retained. Pipelining resulted in an overall error rate of 2%, with 2 personal names retained in output: one initial and a commonly used English term used in medicine. All retained PHI was transformed into standardized medical concepts, making re-identification less likely. Pipelining using deid.pl improved performance of MedLEE in excluding PHI from output and may be a useful strategy for de-identifying clinical data while providing computer-readable output. PMID- 20351898 TI - Medical temporal-knowledge discovery via temporal abstraction. AB - Medical knowledge includes frequently occurring temporal patterns in longitudinal patient records. These patterns are not easily detectable by human clinicians. Current knowledge could be extended by automated temporal data mining. However, multivariate time-oriented data are often present at various levels of abstraction and at multiple temporal granularities, requiring a transformation into a more abstract, yet uniform dimension suitable for mining. Temporal abstraction (of both the time and value dimensions) can transform multiple types of point-based data into a meaningful, time-interval-based data representation, in which significant, interval-based temporal patterns can be discovered. We introduce a modular, fast time-interval mining method, KarmaLego, which exploits the transitivity inherent in temporal relations. We demonstrate the usefulness of KarmaLego in finding meaningful temporal patterns within a set of records of diabetic patients; several patterns seem to have a different frequency depending on gender. We also suggest additional uses of the discovered patterns for temporal clustering of the mined population and for classifying multivariate time series. PMID- 20351899 TI - The effectiveness of a secure email reminder system for colorectal cancer screening. AB - This study looks at the effectiveness of using a secure email system linked to an electronic health record to send reminders to patients in an effort to increase colorectal cancer (CRC) screening rates; 1397 subjects were randomized to receive usual care, a letter reminder or an email reminder which invited patients to pick up a fecal occult blood test at the lab for CRC screening. The number of completed CRC screenings was tallied after a 3 month study period. Rates of CRC screening in the 3 groups were 7.8% in the usual care group, 23.6% in the letter reminder group and 22.7% in the email group. Significant statistical difference was seen between usual care group and letter reminders (p<0.0005) and between usual care and email reminders (p<0.0005) but not between the letter reminders and the email reminders (p=7.11). Email reminders are as effective as letter reminders in increasing CRC screening rates. PMID- 20351900 TI - Assessment of collaboration and interoperability in an information management system to support bioscience research. AB - Biomedical researchers often have to work on massive, detailed, and heterogeneous datasets that raise new challenges of information management. This study reports an investigation into the nature of the problems faced by the researchers in two bioscience test laboratories when dealing with their data management applications. Data were collected using ethnographic observations, questionnaires, and semi-structured interviews. The major problems identified in working with these systems were related to data organization, publications, and collaboration. The interoperability standards were analyzed using a C(4)I framework at the level of connection, communication, consolidation, and collaboration. Such an analysis was found to be useful in judging the capabilities of data management systems at different levels of technological competency. While collaboration and system interoperability are the "must have" attributes of these biomedical scientific laboratory information management applications, usability and human interoperability are the other design concerns that must also be addressed for easy use and implementation. PMID- 20351901 TI - Mission-driven priorities: public health in health information exchange. AB - Developing state- and nationwide health information exchange (HIE) is one of the health priorities defined in the American Recovery and Reinvestment Act. States are expected to take leadership in statewide planning and implementation. To balance limited resources among mandated responsibilities and emerging HIE accountability, we maintain that state public health practitioners must integrate HIE into our mission-driven practice in five priority areas: 1) connecting real time disease surveillance and notifiable case reporting through HIE to better protect citizens; 2) sharing public health-managed clinical information through HIE for preventive services, 3) conduct health education for targeted populations via HIE to promote healthy lifestyles; 4) leverage public health informatics with Medicaid information system to provide quality healthcare; and 5) serve as a regulator for standardized HIT to participate in healthcare reform. We summarize public health's broad practice into "Five P's" and link each domain's historical foundation, current and proposed practices to sustain success. PMID- 20351902 TI - Enhancing an existing clinical information system to improve study recruitment and census gathering efficiency. AB - Information technology can improve healthcare efficiency. We developed and implemented a simple and inexpensive tool, the "Automated Case Finding and Alerting System" (ACAS), using data from an existing clinical information system to facilitate identification of potentially eligible patients for clinical trials and patient encounters for billing purposes. We validated the ACAS by calculating the level of agreement in patient identification with data generated from manual identification methods. There was substantial agreement between the two methods both for clinical trial (kappa:0.84) and billing (kappa:0.97). Automated identification occurred instantaneously vs. about 2 hours/day for clinical trial and 1 hour 10 minutes/day for billing, and was inexpensive ($98.95, one time fee) compared to manual identification ($1,200/month for clinical trial and $670/month for billing). Automated identification was more efficient and cost-effective than manual identification methods. Repurposing clinical information beyond their traditional use has the potential to improve efficiency and decrease healthcare cost. PMID- 20351903 TI - Using clinical questions to structure the content of a web-based information resource for primary care physicians. AB - The Medical Home Portal is a web site aimed at supporting physicians and families in improving the care and outcomes for children with special health care needs (CSHCN) in the Medical Home model. To optimize access to its information and resources, the content has been structured using XML schemas that incorporate relevant clinical questions. This approach guides authors as they develop content and informs the organization of the site, aimed at assuring that users can readily locate needed information and resources. It will also enable direct access to relevant content via "infobuttons" or a questions-based interface, and extraction of content for use in electronic health records or other electronic media. PMID- 20351904 TI - ClinRefLink: implementation of infobutton-like functionality in a commercial clinical information system incorporating concepts from textual documents. AB - Clinical information systems offer an opportunity to provide clinicians with medical reference materials during clinical encounters when the information is most beneficial. Implementation of this "Infobutton" concept has been described by a number of institutions with locally developed clinical information systems and electronic medical records. This article describes the development of an infobutton-like application called ClinRefLink embedded within a commercial clinical information system. ClinRefLink is somewhat unique in that it offers clinicians the option to perform reference searches based on clinical entities identified within narrative documents. In the first 30 days after implementation, 1018 reference searches were performed. The characteristics of the clinicians and the clinical context of the search terms are described. These data support the value of clinical term extraction from narrative documents as a component of an infobutton system. PMID- 20351905 TI - Detecting Underspecification in SNOMED CT concept definitions through natural language processing. AB - Quality assurance and audit issues play a major role in maintening large biomedical terminology, such as SNOMED CT. Several automatized techniques have been proposed to facilitate the identification of weak spots and suggest adequate improvements.In this study, we address a well-known issue within SNOMED CT: Albeit the wording of many free-text concept descriptions suggests a connection to other concepts, they are often not referred to in the logical concept definition.To detect such inconsistencies, we use a semantic indexing approach which maps free text onto a sequence of semantic identifiers. Applied to SNOMED CT concepts without attributes, our technique spots refinable concepts and suggests appropriate attributes, i.e., connections to other concepts. Based on a manual analysis of random samples, we estimate that approximately 18,000 refinable concepts can be found. PMID- 20351906 TI - A highly specific algorithm for identifying asthma cases and controls for genome wide association studies. AB - Our aim was to identify asthmatic patients as cases, and healthy patients as controls, for genome-wide association studies (GWAS), using readily available data from electronic medical records. For GWAS, high specificity is required to accurately identify genotype-phenotype correlations. We developed two algorithms using a combination of diagnoses, medications, and smoking history. By applying stringent criteria for source and specificity of the data we achieved a 95% positive predictive value and 96% negative predictive value for identification of asthma cases and controls compared against clinician review. We achieved a high specificity but at the loss of approximately 24% of the initial number of potential asthma cases we found. However, by standardizing and applying our algorithm across multiple sites, the high number of cases needed for a GWAS could be achieved. PMID- 20351907 TI - Interactive agent based modeling of public health decision-making. AB - Agent-based models have yielded important insights regarding the transmission dynamics of communicable diseases. To better understand how these models can be used to study decision making of public health officials, we developed a computer program that linked an agent-based model of pertussis with an agent-based model of public health management. The program, which we call the Public Health Interactive Model & simulation (PHIMs) encompassed the reporting of cases to public health, case investigation, and public health response. The user directly interacted with the model in the role of the public health decision-maker. In this paper we describe the design of our model, and present the results of a pilot study to assess its usability and potential for future development. Affinity for specific tools was demonstrated. Participants ranked the program high in usability and considered it useful for training. Our ultimate goal is to achieve better public health decisions and outcomes through use of public health decision support tools. PMID- 20351908 TI - QA-driven guidelines generation for bacteriotherapy. AB - PURPOSE: We propose a question-answering (QA) driven generation approach for automatic acquisition of structured rules that can be used in a knowledge authoring tool for antibiotic prescription guidelines management. METHODS: The rule generation is seen as a question-answering problem, where the parameters of the questions are known items of the rule (e.g. an infectious disease, caused by a given bacterium) and answers (e.g. some antibiotics) are obtained by a question answering engine. RESULTS: When looking for a drug given a pathogen and a disease, top-precision of 0.55 is obtained by the combination of the Boolean engine (PubMed) and the relevance-driven engine (easyIR), which means that for more than half of our evaluation benchmark at least one of the recommended antibiotics was automatically acquired by the rule generation method. CONCLUSION: These results suggest that such an automatic text mining approach could provide a useful tool for guidelines management, by improving knowledge update and discovery. PMID- 20351909 TI - Assuring the privacy and security of transmitting sensitive electronic health information. AB - The interchange of electronic health records between healthcare providers and public health organizations has become an increasingly desirable tool in reducing healthcare costs, improving healthcare quality, and protecting population health. Assuring privacy and security in nationwide sharing of Electronic Health Records (EHR) in an environment such as GRID has become a top challenge and concern. The Centers for Disease Control and Prevention's (CDC) and The Science Application International Corporation (SAIC) have jointly conducted a proof of concept study to find and build a common secure and reliable messaging platform (the SRM Platform) to handle this challenge. The SRM Platform is built on the open standards of OASIS, World Wide Web Consortium (W3C) web-services standards, and Web Services Interoperability (WS-I) specifications to provide the secure transport of sensitive EHR or electronic medical records (EMR). Transmitted data may be in any digital form including text, data, and binary files, such as images. This paper identifies the business use cases, architecture, test results, and new connectivity options for disparate health networks among PHIN, NHIN, Grid, and others. PMID- 20351911 TI - Challenges in exchanging medication information: identifying gaps in clinical document exchange and terminology standards. AB - The availability of accurate medication history information is invaluable for making sound therapeutic decisions. The Continuity of Care Document (CCD) could serve as a mechanism for exchanging interoperable medication information between EHRs. We evaluate the feasibility of representing a medication and its underlying components in a Healthcare Information Technology Standards Panel (HITSP) compliant CCD. Our evaluation resulted in successfully mapping 94% of medication entries and greater than 92% of medication component mappings to CCD constraints. We identify gaps and provide recommendations for improving the representational adequacy of the Federal Medication Terminology (FMT) to fully represent orderable medication concepts. PMID- 20351910 TI - Multi-terminology indexing for the assignment of MeSH descriptors to medical abstracts in French. AB - BACKGROUND: To facilitate information retrieval in the biomedical domain, a system for the automatic assignment of Medical Subject Headings to documents curated by an online quality-controlled health gateway was implemented. The French Multi-Terminology Indexer (F-MTI) implements a multiterminology approach using nine main medical terminologies in French and the mappings between them. OBJECTIVE: This paper presents recent efforts to assess the added value of (a) integrating four new terminologies (Orphanet, ATC, drug names, MeSH supplementary concepts) into F-MTI's knowledge sources and (b) performing the automatic indexing on the titles and abstracts (vs. title only) of the online health resources. METHODS: F-MTI was evaluated on a CISMeF corpus comprising 18,161 manually indexed resources. RESULTS: The performance of F-MTI including nine health terminologies on CISMeF resources with Title only was 27.9% precision and 19.7% recall, while the performance on CISMeF resources with Title and Abstract is 14.9 % precision (-13.0%) and 25.9% recall (+6.2%). CONCLUSION: In a few weeks, CISMeF will launch the indexing of resources based on title and abstract, using nine terminologies. PMID- 20351912 TI - Task analysis in action: the role of information systems in communicable disease reporting. AB - In order to improve the design of information systems for notifiable conditions reporting, it is essential to understand the role of such systems in public health practice. Using qualitative techniques, we performed a task analysis of the activities associated with notifiable conditions reporting at a large urban health department. We identified seventeen primary tasks associated with the use of the department's information system. The results of this investigation suggest that communicable disease information management takes place in a dynamic environment where changing needs may require new solutions for system users. Additionally, our work suggests that task analysis, when applied to document the use of a legacy information system, can provide local public health agencies with valuable information about their information management needs, and can become a part of their information management decision-making strategy. PMID- 20351913 TI - A clinical rule editor in an electronic medical record setting: development, design, and implementation. AB - Clinical decision support (CDS) implemented as part of an electronic medical record (EMR) has a well-documented history of improving patient safety and quality of care; however, the difficulties of keeping CDS up to date have also been documented. At Partners HealthCare, we initially implemented CDS reminders in our 'homegrown' EMR system as 'hardcoded' rules. The challenges of updating existing rules and implementing new rules in the hard-coded state, however, soon made this model unsustainable. After evaluating our needs and requirements for rule creation and maintenance, we designed and created a browser-based rule editor that would decrease turnaround time for logic changes, allowing us to respond to CDS requests more efficiently. We have been able to maintain the older reminder rules with the rule editor, and have added a number of new reminders. Our work to date has confirmed the strengths of the editor, but has also identified a few limitations. PMID- 20351914 TI - Residential accessibility to information technology retailers and self reported computer use among patients attending community clinics. AB - The actual mechanisms that maintain the individual disparities in home computer use and internet access that are collectively termed "the digital divide" remain unclear. We hypothesized that geographic accessibility to IT retailers would independently influence community clinic patients self reported use of computers at home thus limiting their ability to access health related information via the internet. To test this we obtained information on the locations of IT retailers in Los Angeles County, California and generated accessibility scores for the patient's home residence. Geographic measures of accessibility to IT retailers independently predicted clinic patient's self reported use of computers at home, and this effect was driven by low income individuals. Our results indicate that the causes of the digital divide are influenced by less commonly considered factors such as local IT retailer availability. PMID- 20351915 TI - A human factors investigation of medication alerts: barriers to prescriber decision-making and clinical workflow. AB - Computerized medication alerts (e.g., drug-drug interaction alerts), which are intended to protect patient safety, should also be designed to support prescriber workflow. However, relatively few studies have examined the use of medication alerts during patient care processes. To assess barriers associated with the use of medication alerts, we directly observed medication prescribing during routine patient care. Prescribers (physicians, pharmacists, and nurse practitioners) were recruited from five outpatient primary care clinics at a major Midwestern Veterans Affairs Medical Center (VAMC). A total of 199 alerts were observed across 91 patients and 20 prescribers during normal patient care tasks. Through inductive qualitative analysis, we identified 15 barriers associated with medication alerts; herein, we describe five of the key barriers in detail. Results may be used to create alert redesigns, which have the potential to more fully support clinical workflow, prescriber decision-making, and patient safety. PMID- 20351916 TI - Early warning and risk estimation methods based on unstructured text in electronic medical records to improve patient adherence and care. AB - In this paper we present risk-estimation models and methods for early detection of patient non-adherence based on unstructured text in patient records. The primary objectives are to perform early interventions on patients at risk of non adherence and improve outcomes. We analyzed over 1.1 million visit notes corresponding to 30,095 Cancer patients, spread across 12 years of Oncology practice. Our risk analysis, based on a rich risk-factor dictionary, revealed that a staggering 30% of the patients were estimated to be at a high risk of non adherence. Our risk classification showed that 2 distinct patient groups, between 26 and 38 (mean risk score, r=0.77, s=0.22), and 75 and 90 (r=0.81, s=0.19) years of age respectively, exhibited the highest risk of nonadherence when compared to the rest. The dominant risk-factors for these two groups, not surprisingly, included psychosocial (e.g. depression, lack of support), medical (e.g. side effects such as pain) and financial issues (e.g. costs of treatment). PMID- 20351917 TI - Provider perceptions of colorectal cancer screening clinical decision support at three benchmark institutions. AB - Implementation of computerized clinical decision support (CDS), and its integration into workflow has not reached its potential. To better understand the use of CDS for colorectal cancer (CRC) screening at benchmark institutions for health information technology (HIT), we conducted direct observation, including opportunistic interviews of primary care providers, as well as key informant interviews and focus groups, to document current challenges to CRC screening and follow-up at clinics affiliated with the Veterans Heath Administration, Regenstrief Institute, and Partners HealthCare System. Analysis revealed six common barriers across institutions from the primary care providers' perspective: receiving and documenting "outside" exam results, inaccuracy of the CDS, compliance issues, poor usability, lack of coordination between primary care and gastroenterology, and the need to attend to more urgent patient issues. Strategies should be developed to enhance current HIT to address these challenges and better support primary care providers and staff. PMID- 20351918 TI - LigerCat: using "MeSH Clouds" from journal, article, or gene citations to facilitate the identification of relevant biomedical literature. AB - The identification of relevant literature from within large collections is often a challenging endeavor. In the context of indexed resources, such as MEDLINE, it has been shown that keywords from a controlled vocabulary (e.g., MeSH) can be used in combination to retrieve relevant search results. One effective strategy for identifying potential search terms is to examine a collection of documents for frequently occurring terms. In this way, "Tag clouds" are a popular mechanism for ascertaining terms associated with a collection of documents. Here, we present the Literature and Genomic Electronic Resource Catalogue (LigerCat) system for exploring biomedical literature through the selection of terms within a "MeSH cloud" that is generated based on an initial query using journal, article, or gene data. The resultant interface is encapsulated within a Web interface: http://ligercat.ubio.org. The system is also available for installation under an MIT license. PMID- 20351919 TI - Towards temporal relation discovery from the clinical narrative. AB - Disease progression and understanding relies on temporal concepts. Discovery of automated temporal relations and timelines from the clinical narrative allows for mining large data sets of clinical text to uncover patterns at the disease and patient level. Our overall goal is the complex task of building a system for automated temporal relation discovery. As a first step, we evaluate enabling methods from the general natural language processing domain - deep parsing and semantic role labeling in predicate-argument structures - to explore their portability to the clinical domain. As a second step, we develop an annotation schema for temporal relations based on TimeML. In this paper we report results and findings from these first steps. Our next efforts will scale up the data collection to develop domain-specific modules for the enabling technologies within Mayo's open-source clinical Text Analysis and Knowledge Extraction System. PMID- 20351920 TI - Can de facto dosing practices bridge the knowledge gap in pediatric medication recommendations? AB - A knowledge gap exists in pediatric medication dosing recommendations due in part to the complexity of researching medication efficacy and safety in children. One possible resource resides in the electronic prescribing practices of pediatric clinicians. In this study, de facto pediatric weight-based levothyroxine dosing practices were studied as a potential source for pediatric medication clinical decision support. This was accomplished by extracting physical exam and prescription details from a well-used clinical data warehouse to calculate weight based dosing practices, and comparing the results with established medication recommendations. Of the 854 prescriptions, 85.2% were under the recommended range, 9.37% were within the range and 5.39% were over the range. Thus, real world prescribing practices may differ from recommendations. Such information may be a valuable resource in pediatric clinical decision support, particularly where practice differs from recommendations, and can help close the knowledge gap where pediatric medication dosing information is sparse or unavailable. PMID- 20351921 TI - Towards a smart object network for clinical services. AB - Radio Frequency Identification (RFID) technology has become prevalent in logistics to support and optimize processes and numerous projects investigate its opportunities and challenges in the clinical context. However, most approaches are focused on one specific application using only a few possibilities of the technology. We describe the development of a smart object network to serve as a generic platform for various clinical services. Based on two disparate scenarios tracking medical devices and transfusion safety - the architecture, implementation issues and prospects of such a platform are discussed. PMID- 20351922 TI - Cognitive analysis of decision support for antibiotic prescribing at the point of ordering in a neonatal intensive care unit. AB - Computerized decision support systems have been used to help ensure safe medication prescribing. However, the acceptance of these types of decision support has been reported to be low. It has been suggested that decreased acceptance may be due to lack of clinical relevance. Additionally, cognitive fit between the user interface and clinical task may impact the response of clinicians as they interact with the system. In order to better understand clinician responses to such decision support, we used cognitive task analysis methods to evaluate clinical alerts for antibiotic prescribing in a neonatal intensive care unit. Two methods were used: 1) a cognitive walkthrough; and 2) usability testing with a 'think-aloud' protocol. Data were analyzed for impact on cognitive effort according to categories of cognitive distance. We found that responses to alerts may be context specific and that lack of screen cues often increases cognitive effort required to use a system. PMID- 20351923 TI - Bayesian modeling of unknown diseases for biosurveillance. AB - This paper investigates Bayesian modeling of unknown causes of events in the context of disease-outbreak detection. We introduce a Bayesian approach that models and detects both (1) known diseases (e.g., influenza and anthrax) by using informative prior probabilities and (2) unknown diseases (e.g., a new, highly contagious respiratory virus that has never been seen before) by using relatively non-informative prior probabilities. We report the results of simulation experiments which support that this modeling method can improve the detection of new disease outbreaks in a population. A key contribution of this paper is that it introduces a Bayesian approach for jointly modeling both known and unknown causes of events. Such modeling has broad applicability in medical informatics, where the space of known causes of outcomes of interest is seldom complete. PMID- 20351924 TI - A comparison of automated methicillin-resistant Staphylococcus aureus identification with current infection control practice. AB - Infections with Methicillin-Resistant Staphylococcus aureus (MRSA) account for almost 20,000 deaths per year. Early identification of patients with MRSA infection or colonization aids in stopping spread. We compared automated identification of MRSA using HL7 lab result messages to current manual infection control practices at a local hospital during July-September 2008. We used data from infection control providers (ICPs), the microbiology lab, and a Regional Healthcare Information Exchange to assess the accuracy of manual and automated methods. Three hundred seventy MRSA cases were identified from July-September 2008. Manual identification recognized 314 (sensitivity 84.9%, positive predictive value 99.4%) MRSA cases and automated detection from HL7 messages identified 341 (sensitivity 92.2%, positive predictive value 98.8%). Automated processing of HL7 lab report messages is a more sensitive method of capturing MRSA cases than current standard infection control practice, with minimal loss of specificity. PMID- 20351925 TI - The cognitive basis of effective team performance: features of failure and success in simulated cardiac resuscitation. AB - Despite a body of research on teams in other fields relatively little is known about measuring teamwork in healthcare. The aim of this study is to characterize the qualitative dimensions of team performance during cardiac resuscitation that results in good and bad outcomes. We studied each team's adherence to Advanced Cardiac Life Support (ACLS) protocol for ventricular fibrillation/tachycardia and identified team behaviors during simulated critical events that affected their performance. The process was captured by a developed task checklist and a validated team work coding system. Results suggest that deviation from the sequence suggested by the ACLS protocol had no impact on the outcome as the successful team deviated more from this sequence than the unsuccessful team. It isn't the deviation from the protocol per se that appears to be important, but how the leadership flexibly adapts to the situational changes with deviations is the crucial factor in team competency. PMID- 20351926 TI - Decision making and physician prescribing characteristics: a pilot study of Japanese physicians. AB - The factors that affect physicians' prescribing remain unclear. Although previous reports suggest that prescription decisions are associated with various clinical situation, most of these studies analyzed simulated patient models rather than actual clinical practice. Here, we retrospectively analyzed actual cases of statin prescription for hyperlipidemia at Tohoku University Hospital between Apr 1, 2004 and Mar 31, 2008. Twelve physicians (6 cardiologists, 3 nephrologist, and 3 diabetologist) made decisions on whether to prescribe statins to 187 patients in 788 visits. As expected, cardiologists started prescribing statins at significantly lower serum total cholesterol levels than other specialists (221.7mg/dL vs. 244.7mg/dL, P<0.05). Interestingly, the total cholesterol levels that triggered prescribing differed significantly among cardiologists (p<0.05). These results suggested that prescription decisions differed not only among specialties but also among individuals. PMID- 20351927 TI - Building a production-ready infrastructure to enhance medication management: early lessons from the nationwide health information network. AB - Poor medication management practices can lead to serious erosion of health care quality and safety. The DHHS Medication Management Use Case outlines methods for the exchange of electronic health information to improve medication management practices. In this case report, the authors describe initial development of Nationwide Health Information Network (NHIN) services to support the Medication Management Use Case. The technical approach and core elements of medication management transactions involved in the NHIN are presented. Early lessons suggest the pathway to improvements in quality and safety are achievable, yet there are challenges for the medical informatics community to address through future research and development activities. PMID- 20351928 TI - A set of preliminary standards recommended for achieving a national repository of clinical decision support interventions. AB - We are investigating the development, implementation and evaluation of clinical decision support (CDS) projects to advance our understanding of how best to incorporate these interventions into the delivery of healthcare. Our overall goal is to explore how the translation of clinical knowledge into CDS and its incorporation into practice can be routinely achieved to improve the quality of healthcare delivered in the U.S.A. Toward this end, we have developed a 7-step model that provides a framework for clinical decision support-related standards that are necessary if we wish to achieve these goals. We believe that if all commercially available EHR systems had the features and functions described in these recommendations, many more healthcare organizations could begin to develop and implement the basic CDS features that are necessary to radically transform the quality, safety, and cost of the current healthcare system. PMID- 20351929 TI - Mayo clinic smoking status classification system: extensions and improvements. AB - This paper describes improvements of and extensions to the Mayo Clinic 2006 smoking status classification system. The new system aims at addressing some of the limitations of the previous one. The performance improvements were mainly achieved through remodeling the negation detection for non-smoker, temporal resolution to distinguish a past and current smoker, and improved detection of the smoking status category of unknown. In addition, we introduced a rule-based component for patient-level smoking status assignments in which the individual smoking statuses of all clinical documents for a given patient are aggregated and analyzed to produce the final patient smoking status. The enhanced system builds upon components from Mayo's clinical Text Analysis and Knowledge Extraction System developed within IBM's Unstructured Information Management Architecture framework. This reusability minimized the development effort. The extended system is in use to identify smoking status risk factors for a peripheral artery disease NHGRI study. PMID- 20351930 TI - What "to-do" with physician task lists: clinical task model development and electronic health record design implications. AB - Clinical task, or "to-do" lists are a common element in the physician document known as signout. Such lists are used to capture and track patient care plan items, supporting daily workflow and collaborative patient management continuity across care transitions. While physician task lists have been shown to be important to patient safety, the tasks themselves have not been systematically examined for their subject matter, structure, or components. A manual sublanguage analysis of 500 signout tasks was conducted, and a hierarchical conceptual model for clinical tasks was inductively constructed. Tasks were classified by action type (Assess, Order, Communicate, Perform) and corresponding components. The most common task action types were Assess and Order. The most common task components were "What" type components such as Tests, including subtypes Laboratory and Imaging. This study yielded several important design considerations for future electronic health record systems that support collaborative clinical task management. PMID- 20351931 TI - Intention to use and actual use of electronic information resources: further exploring Technology Acceptance Model (TAM). AB - Following up a previous study that examined public health students' intention to use e-resources for completing research paper assignments, the present study proposed two models to investigate whether or not public health students actually used the e-resources they intended to use and whether or not the determinants of intention to use predict actual use of e-resources. Focus groups and pre- and post-questionnaires were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that the determinants of intention-to-use significantly predict actual use behavior. Direct impact of perceived usefulness and indirect impact of perceived ease of use to both behavior intention and actual behavior indicated the importance of ease of use at the early stage of technology acceptance. Non-significant intention-behavior relationship prompted thoughts on the measurement of actual behavior and multidimensional characteristics of the intention construct. PMID- 20351932 TI - Impact of prior clinical information in an EHR on care outcomes of emergency patients. AB - A patient's prior clinical information available electronically can be helpful during the care process, particularly in the emergency department (ED). The effect of such information on quality and efficiency of ED patient care has not been adequately studied. This study uses secondary data to investigate its impact on surrogate measures of care quality and efficiency among 6,143 congestive heart failure, diabetic, and asthmatic patients in 3 EDs. Results show that in some subgroups of chronic patients in some EDs, availability of prior clinical information in the electronic health records was associated with significantly lower hospitalization rates, shorter inpatient length of stay, and reduction in the numbers of laboratory tests and diagnostic procedures ordered during the ED visit. However, there were also contradictory effects and lack of significance in other subgroups. The effects vary by ED and disease, highlighting the possibility of contextual differences influencing the effects of such clinical information. PMID- 20351933 TI - Support vector machine-based mucin-type o-linked glycosylation site prediction using enhanced sequence feature encoding. AB - Glycosylation is a common and complex protein post-translational modification (PTM). In particular, mucin-type O-linked glycosylation is abundant and plays important biological functions. The number of determined glycosylation sites is still small and there remains the need of accurate computational prediction for annotation and functional understanding of proteins. PTM site prediction can be formulated as a machine learning task. An important step in applying machine learning to this task is encoding protein fragments as feature vectors. Here we assess existing encoding methods as well as an enhanced encoding method named composition of monomer spectrum (CMS) using support vector machines (SVMs). SVMs employing the existing encoding methods achieved AUC (area under ROC curve) of 90.3-91.3%, and ones employing CMS achieved AUC of 92.4%. Analysis of different encoding methods suggests the potential in further improving the prediction. PMID- 20351934 TI - Embedding the guideline elements model in web ontology language. AB - The Guideline Elements Model (GEM) uses XML to represent the heterogeneous knowledge contained in clinical practice guidelines. GEM has important applications in computer aided guideline authoring and clinical decision support systems. However, its XML representation format could limit its potential impact, as semantic web ontology languages, such as OWL, are becoming major knowledge representation frameworks in medical informatics. In this work, we present a faithful translation of GEM from XML into OWL. This translation is intended to keep the knowledge model of GEM intact, as this knowledge model has been carefully designed and has become a recognized standard. An OWL representation would make GEM more applicable in medical informatics systems that rely on semantic web. This work will also be the initial step in making GEM a guideline recommendation ontology. PMID- 20351935 TI - Enriching PubMed related article search with sentence level co-citations. AB - PubMed related article links identify closely related articles and enhance our ability to navigate the biomedical literature. They are derived by calculating the word similarity between two articles, relating articles with overlapping word content. In this paper, we propose to enrich PubMed with a new type of related article link based on citations within a single sentence (i.e. sentence level co citations or SLCs). Using different similarity metrics, we demonstrated that articles linked by SLCs are highly related. We also showed that only half of SLCs are found among PubMed related article links. Additionally, we discuss how the citing sentence of an SLC explains the connection between two articles. PMID- 20351936 TI - A general framework for dose optimization. AB - Dose optimization is a ubiquitous challenge in clinical practice and includes both pharmacologic and non-pharmacologic interventions. Methods for the statistical assessment of optimum dosing are lacking. We developed a generic framework for dose titration and demonstrated its application in two domains. Optimum warfarin dose was estimated from clinical titration data. In addition, cardiac pacemaker interval optimization was conducted using three conventional techniques. For both data types, optima were obtained from mathematical functions fit to the raw data. The precision of the estimated optima was quantified using bootstrapping. In pacing optimization, the observed precision varied significantly among the techniques, suggesting that impedance cardiography is superior to commonly used echocardiographic methods. The average 95% confidence interval of the estimated optimum warfarin dose was +/-18%, suggesting that titration within this range is of limited utility. By identifying statistically ineffective interventions, objective analysis of optimization data may both improve outcomes and reduce healthcare costs. PMID- 20351937 TI - Visualization and analysis of activities in critical care environments. AB - Critical care environments are inherently complex and dynamic. Assessment of workflow in such environments is not trivial. While existing approaches for workflow analysis such as ethnographic observations and interviewing provide contextualized information about the overall workflow, they are limited in their ability to capture the workflow from all perspectives. This paper presents a tool for automated activity recognition that can provide an additional point of view. Using data captured by Radio Identification (RID) tags and Hidden Markov Models (HMMs), key activities in the environment can be modeled and recognized. The proposed method leverages activity recognition systems to provide a snapshot of workflow in critical care environments. The activities representing the workflow can be extracted and replayed using virtual reality environments for further analysis. PMID- 20351938 TI - Early prediction of reading disability using machine learning. AB - This paper presents application of machine learning methods on a 356 sample dataset for early prediction of reading disability among first graders. A wide array of classifiers consisting of Support Vector Machines, Decision Trees (CART and C4.5), Linear Discriminant Analysis, k Nearest Neighbor and Naive Bayes Classifiers were used in this study. Markov Blanket based feature selection algorithms (HITON-PC and HITON-MB) and wrapper based feature selection algorithms (forward, backward, forward and backward wrapping algorithm and support vector machine recursive feature elimination) were used to select the most relevant features for classification. The results indicate that an AUC score greater than 0.9 can be achieved using SVM classifiers even with a small set of demographics and screening variables. Moreover, a method for generating expert interpretable decision tree models from the high accuracy SVM models is also presented. PMID- 20351939 TI - A Bayesian method for identifying genetic interactions. AB - An important challenge in the analysis of single nucleotide polymorphism (SNP) data is the identification of SNPs that interact in a nonlinear fashion in their association with disease. Such epistatic interactions among genetic variants at multiple loci likely underlie the inheritance of common diseases. We have developed a novel method called the Bayesian combinatorial method (BCM) for detecting combination of genetic variants that are predictive of disease. When compared with the multifactor dimensionality reduction (MDR), a widely used combinatorial method, BCM has significantly greater power to detect interactions and is computationally more efficient. PMID- 20351940 TI - Survey analysis of patient experience using a practice-linked PHR for type 2 diabetes mellitus. AB - Patient experience was assessed by survey as part of a large, randomized controlled trial of a secure, practice-linked personal health record called Patient Gateway at Partners HealthCare in Boston, MA. The subjects were patients with Type 2 diabetes who prepared for their upcoming primary care visit using a previsit electronic journal. The journal generated a diabetes care plan using patient chart information and patient responses to questions in preparation for a scheduled office visit. Review of 37 surveys revealed that a diabetes care plan took 5-9 minutes (modal) to be created by the patient and helped many patients to feel more prepared for their visit (60%) and give more accurate information to their provider (53%). Study limitations included small numbers of survey participants and a bias toward white, better educated patients with better controlled diabetes. Nevertheless, the electronic journal is a promising tool for visit preparation and process improvement. PMID- 20351941 TI - Auditing SNOMED relationships using a converse abstraction network. AB - In SNOMED CT, a given kind of attribute relationship is defined between two hierarchies, a source and a target. Certain hierarchies (or subhierarchies) serve only as targets, with no outgoing relationships of their own. However, converse relationships-those pointing in a direction opposite to the defined relationships while not explicitly represented in SNOMED's inferred view, can be utilized in forming an alternative view of a source. In particular, they can help shed light on a source hierarchy's overall relationship structure. Toward this end, an abstraction network, called the converse abstraction network (CAN), derived automatically from a given SNOMED hierarchy is presented. An auditing methodology based on the CAN is formulated. The methodology is applied to SNOMED's Device subhierarchy and the related device relationships of the Procedure hierarchy. The results indicate that the CAN is useful in finding opportunities for refining and improving SNOMED. PMID- 20351942 TI - Building a shared vision for an online cancer survivorship community. AB - In order to achieve comprehensive, closed-loop care for cancer survivors, new strategies are needed to bring together patients, providers, and support services in local communities. To address this challenge, an online community for cancer survivorship was envisioned and designed collaboratively by cancer survivors, family members, community professionals, and informatics researchers in middle Tennessee. The vision developed by the community members serves as a foundation for medical informatics systems to build capacity in local communities to improve cancer care and social support. Using ecological systems theory and social capital as theoretical frameworks, key themes are identified for the future of communication and collaboration in cancer survivorship. PMID- 20351943 TI - Experiences with web search on medical concerns and self diagnosis. AB - The wealth of medical information on the Web makes it convenient for non-experts to conduct their own diagnosis and healthcare assessment based on limited knowledge of signs, symptoms, and disorders. We present the findings of a survey aimed at exploring laypeoples' activities and experiences with using Web search to pursue explanations for symptoms. Survey findings suggest that the Web may influence anxiety levels and behaviors of those searching for information on undiagnosed conditions. A better understanding of consumer experience regarding the use of the Web to interpret symptoms can assist in the refinement of healthcare content and retrieval. PMID- 20351944 TI - The evolving use of a clinical data repository: facilitating data access within an electronic medical record. AB - We demonstrate the integration of a longitudinal, internally-developed legacy clinical information system with a vendor-based electronic health record application. The expense of developing the interface across systems was minimal, and it was successfully incorporated within the vendor EHR. Users consistently used the legacy data view while using the EHR; usage reached up to 50% of accessed data. Data showing concurrent increases in the use of the legacy data view and adoption of the new EHR suggests the method may improve adoption of the new system. PMID- 20351945 TI - Unsupervised method for extracting machine understandable medical knowledge from a large free text collection. AB - Definitions of medical concepts (e.g diseases, drugs) are essential background knowledge for researchers, clinicians and health care consumers. However, the rapid growth of biomedical research requires that such knowledge continually needs updating. To address this problem, we have developed an unsupervised pattern learning approach that extracts disease and drug definitions from automatically structured randomized clinical trial (RCT) abstracts. In addition, each extracted definition is semantically classified without relying on external medical knowledge. When used to identify definitions from 100 manually annotated RCT abstracts, our medical definition knowledge base has precision of 0.97, recall of 0.93, F1 of 0.94 and semantic classification accuracy of 0.96. PMID- 20351946 TI - A comparison of usability evaluation methods: heuristic evaluation versus end user think-aloud protocol - an example from a web-based communication tool for nurse scheduling. AB - We evaluated a web-based communication tool for nurse scheduling using two common usability evaluation methods, heuristic evaluation and end-user think aloud protocol. We found that heuristic evaluation performed by human-computer interaction (HCI) experts revealed more general interface design problems, while end-users' think-aloud protocols identified more obstacles to task performance. To provide the most effective and thorough evaluation results, a combination of heuristic evaluation and end-user think-aloud protocol is recommended. PMID- 20351947 TI - Scenario-based user testing to guide consumer health informatics design. AB - For consumer health informatics (CHI) interventions to successfully aid laypeople, the interventions must fit and support their health work. This paper outlines a scenario-based human factors assessment of a disease management CHI intervention. Two student users undertook a patient use case and another user followed a nurse use case. Each user completed pre-specified tasks over a ten-day trial, recorded challenges encountered while utilizing the intervention, and logged daily time spent on each task. Results show the scenario-based user testing approach helps effectively and systematically assess potential physical, cognitive, and macroergonomic challenges for end-users, rate the severity of the challenges, and identify mediation strategies for each challenge. In particular, scenario-based user testing aids in identifying challenges that would be difficult, if not impossible, to detect in a laboratory-based usability study. With this information, CHI interventions can be re-designed and/or supplemented, making the intervention more closely fit end-users' work. PMID- 20351949 TI - Functional analysis of interfaces in U.S. military electronic health record system using UFuRT framework. AB - The overall aim of this study is to evaluate the usability of U.S. military electronic health record (EHR) system AHLTA using a systematic work-centered evaluation framework UFuRT --- User, Functional, Representational, and Task Analysis. This paper with the focus of Functional Analysis (FA) of AHLTA explores operationalizable methods to study functions supported by user interfaces. A system hierarchy was created to map and uniquely identify all items on the interfaces. These items were then classified independently by 2 evaluators as Operations or Objects. Operations were further classified as either Domain or Overhead function. With acceptable inter-rater agreement, of the 1996 items in the interfaces, 61% were operations, around one fourth of which were Overhead functions. Overhead functions are hypothesized to be targets to be redesigned for improvements in usability. PMID- 20351948 TI - Uncovering the predictive value of minimum blood glucose through statistical analysis of a large clinical dataset. AB - The clinical utility and risk of strict glycemic control during critical care have been under intense debate. This study aims to elucidate the relationship between glycemic status and patient outcome in an integrated database collected at a tertiary teaching hospital. Clinical data of 16,135 critically ill adult patients with blood glucose measurements were extracted. The lowest blood glucose levels were analyzed against patient outcome. Major findings are 1) mortality of non-diabetic patients who experience persistent hyperglycemia during intensive care rises with increasing hyperglycemia, 2) minimum blood glucose concentration within the 80-110 mg/dL range corresponds to the highest percentage of survival among patients receiving insulin, and 3) inhospital mortality among patients receiving insulin increases as blood glucose concentration falls into the hypoglycemic range. These results suggest that glycemic status and patient outcome are closely associated and the lowest blood glucose concentration that each patient experiences predicts the patient's eventual outcome. PMID- 20351950 TI - Terminology modeling for an enterprise laboratory orders catalog. AB - Laboratory test orders are used in a variety of clinical information systems at Partners HealthCare. At present, each site at Partners manages its own set of laboratory orders with locally defined codes. Our current plan is to implement an enterprise catalog, where laboratory test orders are mapped to reference terminologies and codes from different sites are mapped to each other. This paper describes the terminology modeling effort that preceded the implementation of the enterprise laboratory orders catalog. In particular, we present our experience in adapting HL7's "Common Terminology Services 2 - Upper Level Class Model" as a terminology metamodel for guiding the development of fully specified laboratory orders and related services. PMID- 20351951 TI - Hypothesis-driven story building framework: enhancing iterative process support in clinical diagnostic decision support systems. AB - Clinical diagnosis is an iterative process because of partial and ambiguous information, changing conditions, and resource constraints. Although clinical diagnostic decision support systems have been successfully used to support clinical care, they face certain limitations in supporting clinical diagnosis as an iterative process. An approach is required to enhance the iterative process support in clinical diagnostic decision support systems. We model the clinical diagnosis process as a hypothesis-driven story building, and implement a prototype clinical diagnostic decision support system that is able to generate and evaluate differential diagnoses, narrow and revise the diagnoses based on newly obtained information, and prioritize resources for information seeking. PMID- 20351952 TI - Implementing broad scale childhood immunization decision support as a web service. AB - Timely vaccinations decrease a child's risk of contracting vaccine-preventable disease and prevent disease outbreaks. Childhood immunization schedules may represent the only clinical guideline for which there is official national consensus. So an immunization clinical decision support system (CDSS) is a natural application. However, immunization schedules are complex and change frequently. Maintaining multiple CDSS's is expensive and error prone. Therefore, a practical strategy would be an immunization CDSS as a centralized web service that can be easily accessed by various electronic medical record (EMR) systems. This allows centralized maintenance of immunization guidelines. We have developed a web service, based on Miller's tabular model with modifications, which implements routine childhood immunization guidelines. This immunization web service is currently operating in the Regenstrief Institute intranet and system evaluations are ongoing. We will make this web service available on the Internet. In this paper, we describe this web service -based immunization decision support tool. PMID- 20351953 TI - Rapid response systems in acute hospital care. PMID- 20351954 TI - Portopulmonary hypertension. AB - Portopulmoanry hypertension (POPH) is a form of pulmonary arterial hypertension (PAH) associated with portal hypertension with or without underlying chronic liver disease. POPH is increasingly recognized and recent evidence suggests that it is one of the leading causes of PAH. The pathophysiology of POPH is poorly understood although the pathological changes in pulmonary vasculature in advanced POPH are similar to those seen in idiopathic pulmonary hypertension. The prognosis in patients with liver disease who also suffer from significant POPH is considered to be poor. Higher degree of pulmonary artery pressure (PAP) may preclude a patient from liver transplant as mortality in these patients is high. The treatment with vasodilator therapy has shown to improve both hemodynamics and clinical outcome in POPH in retrospective studies and in some case series. The aim of medical management is to bring PAP <35 mmHg that may make a patient with POPH and advanced liver disease eligible for liver transplant, which otherwise would have been denied because of high PAP. PMID- 20351955 TI - Obstructive sleep apnea and cardiac arrhythmias. AB - Sleep-disordered breathing (SDB), which includes obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway, leading to cessation of breathing while asleep. Cardiac arrhythmias are common problems in OSA patients, although the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined. The presence and complexity of tachyarrhythmias and bradyarrhythmias may influence morbidity, mortality and quality of life for patients with OSA. Although the exact mechanisms underlying the link between OSA and cardiac arrhythmias are not well established, they could be some of the same proposed mechanisms relating OSA to different cardiovascular diseases, such as repetitive pharyngeal collapse during sleep, which leads to markedly reduced or absent airflow, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against an occluded airway and termination by arousal from sleep. These mechanisms elicit a variety of autonomic, hemodynamic, humoral and neuroendocrine responses that evoke acute and chronic changes in cardiovascular function. However, despite substantial research effort, the goals of determining in advance which patients will respond most favorably to certain treatment options (such as continuous positive airway pressure, tracheostomy or cardioversion) and the developing alternative treatments remain largely elusive. Therefore, this literature review aims to summarize a broad array of the pathophysiological mechanisms underlying the relationship between OSA and cardiac arrhythmias and the extent of this association from an epidemiological perspective, thereby attempting to assess the effects of OSA treatment on the presence of cardiac arrhythmias. PMID- 20351956 TI - Home-based pulmonary rehabilitation program: Effect on exercise tolerance and quality of life in chronic obstructive pulmonary disease patients. AB - BACKGROUND: A key component in the management of chronic obstructive pulmonary disease (COPD) patients is pulmonary rehabilitation (PR), the corner stone of which is exercise training. AIM: This study aims to evaluate the effect of a two months, home-based PR program with outpatient supervision every two weeks, on exercise tolerance and health-related quality of life (HRQL) using Arabic translated standardized generic and specific questionnaires in COPD patients recently recovered from acute exacerbation, DESIGN: Randomized clinical trial. SETTING AND SUBJECTS: A total of 39 COPD patients who recovered from acute exacerbation were randomly allocated either a two-month home-based PR program in addition to standard medical therapy or standard medical therapy alone in the period between July 2008 and March 2009. METHODS: Pulmonary function tests (PFTs), six-minute walk distance (6-MWD) test, Arabic-translated chronic respiratory disease questionnaire-self administered standardized format (CRQ-SAS) and quality of life scale Short Form (SF-36) were compared between 25 patients with moderate to severe COPD who underwent a two-month PR program (group 1) and 14 COPD patients who did not (group 2). RESULTS: Group 1 showed significant improvement in the 6-MWD, and HRQL scores at two months compared with the usual care patients in group 2 (P less than 0.05). Improvement in both CRQ-SAS and SF 36 scores were statistically significant and comparable in group 1. CONCLUSION: The supervised, post discharge, two-month home-based PR program is an effective non pharmacological intervention in the management of stable patients with COPD. The 6-MWD is a simple, inexpensive and safe test to assess physical and functional capabilities among COPD patients. HRQL can be measured in patients with COPD either by disease-specific tools that have been specifically designed for use in patients with respiratory system disorders or by generic HRQL tools that can be used across populations with a variety of medical conditions. The Arabic-translated CRQ-SAS is a new tool for assessment of Arabic-speaking patients with chronic respiratory diseases. PMID- 20351957 TI - Percutaneous tracheostomy in critically ill patients: 24 months experience at a tertiary care hospital in United Arab Emirates. AB - OBJECTIVE: We assessed the safety and complications related to percutaneous tracheostomy (PCT) without bronchoscopic guidance in our intensive care unit (ICU). METHODS: The prospective data over a period of 24 months were collected for patients who underwent PCT. Major, minor and long-term complications were recorded. The parameters recorded were: age, gender, Glasgow Coma Scale (GCS) score on the day of tracheostomy, acute physiology and chronic health evaluation II (APACHE) score, and predicted mortality based on score on admission and on the day of procedure, number of days on ventilator before and after the procedure, total number of days in the hospital before the final outcome, number of successful decannulations and mortality. The patients were stratified in two groups of survivors and nonsurvivors. RESULTS: A total of 117 patients underwent PCT. Overall mean GCS and APACHE-II scores before PCT were 7 +/- 3 and 16 +/- 5, respectively. The only significant difference was APACHE-II score and the predicted mortality based on APACHE-II score on the day of PCT, which was higher amongst the nonsurvivors (P = 0.008 and P = 0.006). All 57 (49%) survivors were successfully decannulated with mean post tracheostomy days of 24 +/- 15. The major complication observed was three episodes of major bleeding. Only six patients had an episode of desaturation during the procedure and there were three episode of accidental puncturing of endotracheal (ET) tube pressure cuff. During subsequent follow-up in hospital, six patients developed stomal cellulitis. CONCLUSIONS: PCT without bronchoscopic guidance can be performed safely by carefully selecting patients and having an experienced team High APACHE score on the day of procedure may lead to poor outcome. PMID- 20351958 TI - Lung cancer at a University Hospital in Saudi Arabia: A four-year prospective study of clinical, pathological, radiological, bronchoscopic, and biochemical parameters. AB - OBJECTIVES AND BACKGROUND: Lung cancer accounts for 4% of all newly diagnosed cancers in Saudi Arabia. The pattern of presentation is unknown. The objectives of this study were to assess the clinical, radiological, pathological, biochemical and bronchoscopic abnormalities in lung cancer patients and to compare our findings with those reported in the literature. METHODS: A total of 114 patients with proven lung cancer were selected for the study. A questionnaire concerning patients' demographic data was obtained; the abnormalities and the cell types of lung cancer were recorded prospectively in each subject. RESULTS: A total of 114 patients with lung cancer were studied. Mean age +/- SD was (59.8 +/ 10.8) years, and (71.1%) were smokers and 95.1% of them were male, (90.1%) smoked >20 pack/yr (96.2%) for 20 years or more. Cough (76.3%) and clubbing (40.4%) were the most common symptom and physical abnormality respectively. The right lung (64.9%) was more commonly affected than the left (37.7%). Metastases were present in (49.1%) at presentation. The right and left upper bronchi (24% vs. 16%) were the mostly affected. Hypercalcemia was more common in squamous cell, while hyponatremia was more common in adenocarcinoma, and small cell. Squamous cell carcinoma was the most common cell type (51.8%) and significantly associated with smoking (P <= 0.001) CONCLUSION: Squamous cell carcinoma was the most common cell type, and significantly associated with smoking. The incidence of metastasis was high at presentation. The right lung and right upper bronchus were often affected. Hypercalcemia and hyponatremia were the most common biochemical abnormalities. PMID- 20351959 TI - Association and symptom characteristics of irritable bowel syndrome among bronchial asthma patients in Kuwait. AB - CONTEXT: Excess prevalence of irritable bowel syndrome in asthma has been reported, suggesting a link between these two conditions. AIMS: To investigate the association between irritable bowel syndrome (IBS) and asthma, and explore the symptoms of IBS among asthma patients in Kuwait. SETTINGS AND DESIGN: Case control study. METHODS: In a tertiary center, for allergy and asthma, 138 patients aged 20-65 years, with asthma, diagnosed clinically and by spirometry, were compared with 145 healthy, non-asthmatic controls matched for age, gender and nationality. Cases and controls completed a self-administered questionnaire of irritable bowel syndrome diagnosis (ROME II criteria). STATISTICAL ANALYSIS USED: The data were analyzed using SPSS software, and proportions were tested with Chi-square or Fisher's test. Odds ratio (OR) with 95% Confidence Interval (CI) were calculated to identify the associated risk factors. The demographic variables were selected for logistic regression analysis. RESULTS: A significantly large proportion (39.13%) of asthmatics had IBS as compared to 7.93% controls (P < 0.001). A higher proportion of females with IBS were observed in cases and controls (74%, 61.54%). IBS was seen in 87% cases using inhalers, and in 13% with additional oral theophylline (P < 0.001). As many as 66.6% cases, had IBS with relatively short duration of asthma (1-5 years, P < 000). Predominant symptoms of IBS in asthmatics were abdominal discomfort or distension (64.8% vs. 11.5%), (P < 0.000, OR = 14.1; 95%CI: 3.748-53.209), bloated feeling of abdomen (74.1% vs. 34.62% (P < 0.001, OR = 5.38; 95%CI:1.96-14.84)), increased frequency of stools (63%, P < 0.006). CONCLUSIONS: Irritable bowel syndrome in asthmatics was significantly high, more in the female asthmatics. Abdominal discomfort, persistent bloated feeling, increased frequency of passing stools were the most common IBS symptoms observed. PMID- 20351960 TI - Performance of QuantiFERON-TB Gold test compared to tuberculin skin test in detecting latent tuberculosis infection in HIV- positive individuals in Iran. AB - BACKGROUND: There is limited data about the performance of QuantiFERON-TB Gold (QFT-G) test in detecting latent tuberculosis infection (LTBI) in our region. We intended to determine the performance of QFT-G compared to conventional tuberculin skin test (TST) in detecting LTBI in HIV-positive individuals in Iran. METHODS: This study was conducted in a HIV clinic in Tehran, Iran in April 2007. A total of 50 consecutive HIV-positive patients, not currently affected with active tuberculosis (TB), were recruited; 43 (86%) were male. The mean age was 38 +/- 7.2 years (21-53). All had history of Bacillus Calmette Guerin (BCG) vaccination. A TST with purified protein derivative (PPD) and whole-blood interferon-gamma release assay (IGRA) in reaction to ESAT-6 and CFP-10 antigens was performed and measured by enzyme-linked immuno-sorbent assay (ELISA). The agreement between TST and QFT-G results were analyzed using Kappa test. RESULTS: A total of 36 (72%) patients had negative and 14 (28%) revealed positive TST. For QFT-G, 20 (40%) tested positive, 19 (38%) tested negative, and the results in 11 cases (22%) were indeterminate. A total of 14 (28%) patients had a CD4 count of <200. Of the 14, TST + group, 12 had QFT-G +, only one case TST+/QFT-G-, and QFT G was indeterminate in one TST positive case. Of the 36 patients with negative TST tests, 8 (22%) had positive GFT-G and 10 (28%) yielded indeterminate results. There was no association between a positive TST and receiving highly active anti retroviral therapy (HAART) or absolute CD4 counts. Similarly, the association between QFT-G results and receiving HAART or CD4 counts was not significant (P = 0.06). Although TST results were not significantly different in patients with CD4 < 200 vs. CD4 >200 (P = 0.295), association between QFT-G results and CD4 cutoff of 200 reached statistical significance (P = 0.027). Agreement Kappa coefficient between TST and QFT-G was 0.54 (Kappa = 0.54, 95% CI = 38.4-69.6,P < 0.001). CONCLUSION: Detecting LTBI in HIV-positive individuals showed moderate agreement between QFT-G and LTBI in our study. Interestingly, our findings revealed that nontuberculous mycobacteria and prior BCG vaccination have minimal influence on TST results in HIV patients in Iran. PMID- 20351961 TI - Thoracoscopic enucleation of esophageal leiomyoma in patient with MEN I syndrome. AB - Minimal invasive thoracic surgery is growing rapidly and may become the standard of care for certain diseases. Its benefits over traditional surgery, including reduced morbidities and hospital stay, have been well established in several reports. We herein report a case of midesophageal leiomyoma in a patient with MEN I syndrome successfully enucleated by thoracoscopy highlighting the technical details of the procedure. PMID- 20351962 TI - Splenic abscess as a paradoxical response to chemotherapy in tuberculous pleural effusion. AB - We report a rare case of tuberculous pleural effusion that developed multiple splenic abscesses after antituberculosis chemotherapy. She responded to addition of oral corticosteroid to antituberculosis regimen. The relevant literature, regarding pathogenesis and clinical importance of recognizing a paradoxical response, is discussed. PMID- 20351963 TI - Endobronchial mass in an elderly smoker. PMID- 20351964 TI - Mendelian susceptibility to mycobacterial infection should be ruled out in Mycobacterium chelonae empyema. PMID- 20351965 TI - Scale of dyspnea in COPD: User friendly? PMID- 20351966 TI - Author's reply. PMID- 20351967 TI - Bilateral sternoclavicular joint tubercular cold abscess. PMID- 20351968 TI - "Old is gold". PMID- 20351969 TI - Be original - You were born one. PMID- 20351970 TI - The chemical composition of mineral trioxide aggregate. AB - Mineral trioxide aggregate (MTA) is composed of Portland cement, with 4:1 addition of bismuth oxide added so that the material can be detected on a radiograph. The cement is made up of calcium, silicon and aluminium. The main constituent phases are tricalcium and dicalcium silicate and tricalcium aluminate. There are two commercial forms of MTA, namely the grey and the white. The difference between the grey and the white materials is the presence of iron in the grey material, which makes up the phase tetracalcium alumino-ferrite. This phase is absent in white MTA. Hydration of MTA occurs in two stages. The initial reaction between tricalcium aluminate and water in the presence of calcium sulphate results in the production of ettringite. Tricalcium and dicalcium silicate react with water to produce calcium silicate hydrate and calcium hydroxide, which is leached out of the cement with time. PMID- 20351971 TI - Effect of thermocycling on the flexural strength of porcelain laminate veneers. AB - AIM: The aim of this study was to examine the impact of thermocycling on the flexural strength and development of surface flaws on the glazed surface of porcelain laminate veneer restorations with and without resin luting cement. MATERIALS AND METHODS: 80 Vitadur alpha dentin porcelain discs (10 mm diameter, 0.9 mm thickness) were glazed on one side and divided into two groups: A (porcelain laminate veneer only without resin luting cement) and B (porcelain laminate veneer luted with resin cement), each containing 40 discs. The discs in groups A and B were then thermocycled at different temperatures and were subjected to SEM analysis to evaluate the effect of thermocycling on crack propagation. Mean flexural strength was determined by using the ball-on-ring test. Student's t -test was used to find out the difference between strength values of the thermocycled porcelain discs and discs luted with resin cement. RESULTS: SEM analysis revealed crack propagation in the subgroups subjected to extremes of temperature, i.e., 4 +/- 1 degrees C, 37 +/- 1 degrees C and 4 +/- 1 degrees C, 65 +/- 1 degrees C in the porcelain laminate veneers luted with resin cement. Flexural strength analysis revealed superior flexural strength for porcelain laminate veneers: 88.58 +/- 6.94 MPa when compared to porcelain laminate veneers luted with resin cement: 8.42 +/- 2.60 MPa. Results were tabulated and statistically analyzed using Student's t -test. CONCLUSION: Laminate veneer specimens exhibited greater flexural strength than those which were luted with resin cements. Laminate veneer specimens luted with resin cement and subjected to extremes of temperature, 4 +/- 1 degrees C and 37 +/- 1 degrees C and 4 +/- 1 degrees C and 65 +/- 1 degrees C, showed a marked decrease in flexural strength. After thermocycling at extremes of temperature, laminate veneer specimens luted with resin cement showed crack propagation. Fit of laminate veneers cannot / should not be compensated by the thickness of luting agent. PMID- 20351972 TI - Assessment of antibacterial activity of self-etching dental adhesive systems: An in vitro study. AB - AIM: To evaluate and compare the antibacterial activity of polymerized, two-step, self-etching and one-step, self-etching adhesive systems by using the direct contact test after one, seven, and fourteen days. MATERIALS AND METHODS: The direct contact test was used to evaluate the antibacterial activity of Clearfil Protect Bond, Adper SE Plus, Clearfil SE Bond, and Adper Easy One on Streptococcus mutans after aging the samples in phosphate-buffered saline for one, seven, and fourteen days. Statistical analysis included the one-way Anova and Tukey's multiple comparison tests. RESULTS: Among the tested materials, Clearfil Protect Bond exhibited an antibacterial effect for seven days when in contact with S. mutans. None of the adhesive systems exhibited any antibacterial effect after 14 days. CONCLUSION: The incorporation of antibacterial agents into dentine-bonding agents may become an essential factor in inhibiting residual bacteria in the cavity following a cavity disinfection procedure, and it could be recommended in situations where total disinfection of cavity is not accomplished due to lack of accessibility. PMID- 20351973 TI - Comparative evaluation of self-etching primers with fourth and fifth generation dentin-bonding systems on carious and normal dentin substrates: An in vitro shear bond strength analysis. AB - AIM: The aim of this study was to test the hypothesis that bonding to caries affected dentin would yield strengths that are lower than bond strengths achievable when bonded to normal dentin. Dentin-bonding systems used in this study were fourth and fifth generation as well as self-etching primers. MATERIALS AND METHODS: Forty-eight freshly extracted mandibular and maxillary molars were selected of which 24 were caries-affected teeth and the remaining were noncarious teeth. Random sampling was done with eight teeth in each group based on the bonding system used. In caries-affected teeth, the soft, stainable, caries infected dentin was excavated using a caries detector dye whereas the hard, caries-affected, nonstainable dentin was retained. All the teeth were subsequently mounted in a suitable acrylic mould. Prepared teeth were restored with a single composite resin, using three different dentin bonding systems. These prepared specimens were transferred to a Hounsfield tensometer to measure the shear bond strength. The results obtained were analyzed using Anova, Student's unpaired t-test, and Student Neuman Keulis test. RESULTS: The results showed that the self-etching primer required the highest mean shear load compared to the fifth and fourth generation dentin-bonding systems in both normal dentin and caries-affected dentin. CONCLUSION: Bond strength to dentin depends on whether the dentinal tubule is open or occluded. Within the limitations of this study, it was observed that bond strength to caries-affected dentin was low compared to normal dentin. PMID- 20351974 TI - Evaluation of the effects of the oxygen-inhibited layer on shear bond strength of two resin composites. AB - AIM: The rising demand for aesthetic adhesive restorations has led to the wide use of composites. Multilayer techniques are recommended for the success of these restorations. However, this technique of layering causes the problem of interlayer adhesion, thus supporting the influence of the oxygen-inhibited layer. This study sought to test the hypothesis that the oxygen-inhibited layer increases the shear bond strength of composite resin by allowing the resins on both sides to cross the interface and form an interdiffusion zone. MATERIALS AND METHODS: A microhybrid composite resin, Charisma, and a nanofill composite resin, Solare, were used in this study. Cylindrical specimens of the composites of 5 mm diameter and 6 mm height were prepared and embedded in acrylic resin moulds after curing. Curing was done in an argon atmosphere to prevent the formation of the oxygen-inhibited layer. To clinically simulate an inert atmosphere, a cellophane matrix strip was used during the process of curing. RESULTS: Shear bond strength of the specimens was tested using a universal testing machine and the results were tabulated and statistically analyzed. PMID- 20351975 TI - Clinical evaluation of carbon fiber reinforced carbon endodontic post, glass fiber reinforced post with cast post and core: A one year comparative clinical study. AB - AIM: Restoring endodontically treated teeth is one of the major treatments provided by the dental practitioner. Selection and proper use of restorative materials continues to be a source of frustration for many clinicians. There is controversy surrounding the most suitable choice of restorative material and the placement method that will result in the highest probability of successful treatment. This clinical study compares two different varieties of fiber posts and one cast post and core in terms of mobility of crown margin under finger pressure, recurrent caries detected at the crown margin, fracture of the restoration, fracture of the root and periapical and periodontal pathology requiring crown removal over the period of 12months as evaluated by clinical and radiographical examination. MATERIALS AND METHODS: 30 root canal treated, single rooted maxillary anterior teeth of 25 patients in the age range of 18-60 years where a post retained crown was indicated were selected for the study between January 2007 and August 2007; and prepared in a standard clinical manner. It was divided into 3 groups of 10 teeth in each group. After post space preparation, the Carbon fiber and Glass fiber reinforced posts were cemented with Scotch bond multipurpose plus bonding agent and RelyX adhesive resin cement in the first and second groups respectively. The Cast post and cores were cemented with Zinc Phosphate cement in the third group. Following post- cementation, the preparation was further refined and a rubber base impression was taken for metal-ceramic crowns which was cemented with Zinc Phosphate cement. A baseline periapical radiograph was taken once each crown was cemented. All patients were evaluated after one week (baseline), 3 months, 6 months and one year for following characteristics mobility of crown margin under finger pressure, recurrent caries detected at the crown margin, fracture of the restoration, fracture of the root and periapical and periodontal pathology. RESULTS: Results after 12 months showed that none of the restorations among groups of cast post and core, carbon fiber reinforced post and glass fiber reinforced post with composite core restorations failed in terms of recurrent caries detected at the crown margin, fracture of the restoration, fracture of the root and periapical and periodontal pathology. One case of cast post and core and one case of carbon fiber reinforced post with composite core restorations showed slight mobility of crown margin under finger pressure at 12(th) month recall but all the cases of glass fiber post with composite core restorations did not show any signs of mobility of crown margin under finger pressure at all the recall periods on clinical and radiographical examination. CONCLUSION: From this 12 months clinical evaluation of all the cases in the 3 groups comprising of cast post and core; carbon fiber reinforced post with composite core and glass fiber reinforced post with composite core restored with porcelain fused to metal crowns, it is concluded that glass fiber reinforced post with composite core when used in single rooted upper anterior teeth are associated with a higher success rate in restoration of endodontically treated teeth. PMID- 20351976 TI - Endodontic management of a maxillary second premolar with an S-shaped root canal. AB - Complex and unusual root canal morphology is an often occurring phenomenon. Understanding the unusual root canal morphology contributes to success in endodontic treatment. One such variant root canal morphology is the 'S' shaped or bayonet shaped root canal. This case report discusses endodontic treatment of a maxillary second premolar with an 'S' shaped root canal. PMID- 20351977 TI - Platelet-rich plasma: support for its use in wound healing. AB - Previous topical growth factor studies have shown that recombinant human platelet derived growth factor-BB isomer (rhPDGF-BB) is an efficacious treatment of chronic diabetic foot ulceration. A newer treatment, autologous platelet-rich plasma (PRP), represents a greater similarity to the natural healing process as a composite of multiple growth factors, is safe due to its autologous nature, and is produced as needed from patient blood. A review of the literature shows few studies performed with scientific rigor, although the safety of PRP appears to be validated. As the use of PRP increases, additional studies may establish PRP as an efficacious treatment modality and guide future treatment of chronic diabetic foot ulceration. PMID- 20351978 TI - Recent advances in postoperative pain management. AB - Good pain control after surgery is important to prevent negative outcomes such as tachycardia, hypertension, myocardial ischemia, decrease in alveolar ventilation, and poor wound healing. Exacerbations of acute pain can lead to neural sensitization and release of mediators both peripherally and centrally. Clinical wind up occurs from the processes of N-Methyl D-Aspartate (NMDA) activation, wind up central sensitization, long-term potentiation of pain (LTP), and transcription dependent sensitization. Advances in the knowledge of molecular mechanisms have led to the development of multimodal analgesia and new pharmaceutical products to treat postoperative pain. The new pharmacological products to treat postoperative pain include extended-release epidural morphine and analgesic adjuvants such as capsaicin, ketamine, gabapentin, pregabalin dexmetomidine, and tapentadol. Newer postoperative patient-controlled analgesia (PCA) in modes such as intranasal, regional, transdermal, and pulmonary presents another interesting avenue of development. PMID- 20351979 TI - Amelioration of symptoms and reduction of VIP levels after hepatic artery chemoembolization in a patient with sandostatin resistant VIPoma. AB - Vasoactive intestinal polypeptide secreting islet cell tumors (VIPomas) are neuroendocrine tumors that secrete excessive amounts of vasoactive intestinal polypeptide (VIP) that cause distinct syndromes characterized by large-volume diarrhea, hypokalemia, and dehydration. The annual incidence of these tumors is estimated to be about one per 10,000,000 individuals in the general population. We report a successful treatment of VIPoma with hepatic chemoembolization of a metastatic hepatic lesion evidenced by a reduction of VIP levels and resolutions of symptoms in a patient with pancreatic VIPoma unresponsive to increased doses of an octreotide analog. PMID- 20351980 TI - From chattel to consenter: adolescents and informed consent: 2009 Grover Powers Lecture. AB - Angela Holder was to give the Grover Powers Memorial Lecture at the weekly Grand Rounds conducted by the Yale Department of Pediatrics on Wednesday, May 27, 2009, but unfortunately, she died one month earlier, on April 22, leaving behind her prepared address, "From Chattel to Consenter: Adolescents and Informed Consent," which she had regarded as the pinnacle of a remarkable career, much of it spent at Yale. As the Grover Powers honoree, the department's highest honor, Ms. Holder was only the fourth woman of 46 recipients and the first who was not a physician. On the date scheduled for her address, tributes were presented by her son, John Holder, and her longtime colleague, Dr. Robert Levine, co-founder of Yale's Interdisciplinary Bioethics Center. Their comments follow Angela Holder's completed but undelivered Grover Powers address. - Myron Genel, MD, Professor Emeritus of Pediatrics. PMID- 20351981 TI - Five classic articles in public health. AB - In this brief review, Dr. Jonathan Borak comments on five seminal papers that helped shape the fields of epidemiology and public health. These papers include Hill's criteria for inferring causality; the first proof of the multistage theory of cancer; the first evidence that subclinical lead exposures can cause neurobehavioral impairment in children; a simple yet robust study that had a major influence on setting current air pollution policies; and a landmark review of the general public's perception of risk in relation to actual public health hazard. PMID- 20351982 TI - The subspecialization conundrum. PMID- 20351983 TI - Practical issues in picture archiving and communication system and networking. AB - Picture Archiving and Communication System (PACS) is a key workflow tool in the functioning of radiology departments worldwide, today, and its utilization is rapidly growing in India. The key challenges in PACS implementation are related to vendor and feature selection, integration with the existing HIS, user training, maintenance and scalability to meet increasing demands. Additionally, the networking requirements that PACS imposes on hospital networks are not insignificant. This article attempts to review these issues from the standpoint of what a prospective or new user needs to know. PMID- 20351984 TI - Pictorial essay: Orbital tuberculosis. AB - Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment. PMID- 20351985 TI - Primary laryngeal tuberculosis mimicking laryngeal carcinoma: CT scan features. AB - Laryngeal tuberculosis is a rare disease. It is almost always associated with pulmonary tuberculosis. It occurs generally in adults without BCG vaccination or in cases of the acquired immune deficiency syndrome. On laryngoscopy and imaging, it often simulates laryngeal carcinoma, and confirmation is always histological. We report the case of a 36-year-old man who presented to our hospital with dysphonia and dysphagia. Laryngoscopy revealed a lesion of the left vocal cord and the ventricular strip. CT scan found focal, regular thickening of the left vocal cord, associated with irregular thickening of the posterior laryngeal wall. A biopsy confirmed the diagnosis of tuberculosis. PMID- 20351987 TI - Color doppler evaluation of cerebral-umbilical pulsatility ratio and its usefulness in the diagnosis of intrauterine growth retardation and prediction of adverse perinatal outcome. AB - OBJECTIVE: The aim of our study was to evaluate the usefulness of the pulsatility index (PI) of the umbilical artery (UA) and that of the fetal middle cerebral artery (MCA), as well as the ratio of the MCA PI to the UA PI (C/U ratio), in the diagnosis of small-for-gestational-age (SGA) fetuses and in the prediction of adverse perinatal outcome. MATERIALS AND METHODS: The study population comprised 90 pregnancies of 30-41 weeks gestation that had been diagnosed clinically as intrauterine growth retardation (IUGR) over a period of 1 year. The UA PI and the MCA PI as well as the C/U ratio were calculated. RESULTS: Of the 90 pregnancies in the study, 24 showed abnormal UA PI. Among these, 21 (87.5%) were SGA and 19 (79.2%) had adverse perinatal outcome. Of the four of the 90 pregnancies that showed abnormal MCA PI, all were SGA and had adverse perinatal outcome. Similarly, of the 20 out of 90 pregnancies that showed abnormal C/U ratio (<1.08), all 20 (100%) were SGA and had adverse perinatal outcome. The results were correlated with parameters of fetal outcome. CONCLUSION: INFERENCES DRAWN FROM THE STUDY WERE: (1) The C/U ratio is a better predictor of SGA fetuses and adverse perinatal outcome than the MCA PI or the UA PI used alone, (2) The UA PI can be used to identify IUGR per se and (3) The MCA PI alone is not a reliable indicator for predicting fetal distress. PMID- 20351986 TI - Forced diuresis and dual-phase F-fluorodeoxyglucose-PET/CT scan for restaging of urinary bladder cancers. AB - CONTEXT: The results of (18)F-fluorodeoxyglucose (FDG)-PET imaging carried out with the current standard techniques for assessment of urinary tract cancers have been reported to be less than satisfactory because of the urinary excretion of the tracer. AIMS: To investigate the role of dual-phase FDG-PET/CT in the restaging of invasive cancers of the urinary bladder, with delayed imaging after forced diuresis and oral hydration as the scanning protocol. SETTINGS AND DESIGN: FDG-PET has been considered to be of limited value for the detection of urinary tract cancers because of interference by the FDG excreted in urine. We investigated the efficacy of delayed FDG-PET/CT in the restaging of invasive bladder cancer, with imaging performed after intravenous (IV) administration of a potent diuretic and oral hydration. MATERIALS AND METHODS: Twenty-nine patients with invasive cancer of the urinary bladder were included in this study. Patients were divided into two groups: Group I (22 patients) included cases with invasive bladder cancer who had not undergone cystectomy and group II (seven patients) included cases with invasive bladder cancer who had undergone cystectomy and urinary diversion procedure. All patients underwent FDG-PET/CT scan from the skull base to the mid-thighs 60 min after IV injection of 370 mega-Becquerel (MBq) of FDG. Additional delayed images were acquired 60-90 min after IV furosemide and oral hydration. PET/CT data were analyzed as PET and CT images studied separately as well as fused PET/CT images and the findings were recorded. The imaging findings were confirmed by cystoscopy, biopsy or follow-up PET/CT. RESULTS: The technique was successful in achieving adequate washout of urinary FDG and overcame the problems posed by the excess FDG in the urinary tract. Hypermetabolic lesions could be easily detected by PET and precisely localized to the bladder wall, perivesical region and pelvic lymph nodes. PET/CT delayed images were able to demonstrate 16 intravesical lesions (in 13 patients), with excellent clarity. Lymph node metastases were detected in a total of six patients. Of these, in two patients, FDG-avid lymph nodes were evident only in the delayed images. The information provided by the postdiuretic delayed images changed the PET/CT interpretation in 14 patients of invasive bladder cancer: Recurrent bladder lesions were identified in 12 patients, pelvic lymph node metastasis (only) in one patient and bladder lesion as well as lymph node metastasis in one patient. Distant metastases were detected by PET/CT in two cases. CT scan was false-negative for early recurrence in the bladder wall for seven of 16 lesions. CT also showed two false-positive lesions. There were no false-positives with PET. CONCLUSIONS: Detection of recurrent disease in cases of invasive bladder cancer can be significantly improved by using FDG-PET/CT, with delayed imaging following forced diuresis and oral hydration. Composite PET/CT is superior to CT alone for the restaging of invasive bladder cancers. PMID- 20351988 TI - Embolization of cranial dural arteriovenous fistulae with ONYX: Indications, techniques, and outcomes. AB - OBJECTIVES: The purpose of this study was to establish the role of the liquid embolic agent, ONYX, in the treatment of cranial dural arteriovenous fistulae (DAVFs) and to redefine the indications, techniques and outcomes of treatment with ONYX. MATERIALS AND METHODS: This is a retrospective study of 25 DAVF patients who underwent endovascular treatment with ONYX between February 2006 and July 2008. All patients of DAVF presenting in this period were treated with ONYX. RESULTS: Anatomic cure (i.e., complete angiographic closure of the fistula) was achieved in a single session and through a single arterial pedicle injection in 21 out of 25 patients (cure rate of 84%). Out of four patients with residual fistulae, one achieved cure that was evident on a control angiogram obtained at 3 months while three had no vascular access for further embolization and so were referred for radiosurgery. There was only one recurrence seen in angiograms obtained at the end of one year and this patient was re-embolized successfully with ONYX. Complications were seen in two patients. CONCLUSION: ONYX embolization of DAVFs has revolutionized the endovascular treatment of DAVFs, achieving high cure rates in a single session with minimal complications. Transarterial ONYX embolization should be the first option for all locations, except cavernous DAVFs. PMID- 20351989 TI - Image-guided percutaneous drainage of an emphysematous bulla with a fluid level. AB - We report here a case of a large emphysematous bulla with a fluid level that was managed successfully by percutaneous catheter drainage in a 50 year-old man with chronic obstructive airway disease. PMID- 20351990 TI - Refractory post visual internal urethrotomy bleeding managed by angioembolization. AB - Post visual internal urethrotomy (VIU) bleeding is usually treated successfully with local compression. Angioembolization for post VIU bleeding has not been previously reported to the best of our knowledge. This is a case report of a 55 year-old man who was referred with persistent per urethral bleeding around a Foley catheter, three days following VIU. When standard methods of treatment were unsuccessful, the bleeding was controlled by embolizing the bulbourethral artery with polyvinyl alcohol (PVA) particles. PMID- 20351991 TI - Visualization of gastric varices using angiographic C-arm CT during retrograde transvenous sclerotherapy. AB - During retrograde transvenous sclerotherapy for gastric varices, sufficient opacification of the target varices on venography is essential for successful treatment. However, venography sometimes cannot identify target varices due to overlapping adjacent collateral vessels or leakage of contrast medium to other outflow veins. We report how C-arm CT images acquired using a flat-panel detector angiography system helped to identify target varices and predict the distribution of a sclerosant, which resulted in safer sclerotherapy and increased operator confidence. PMID- 20351992 TI - Metaphyseal bands in osteogenesis imperfecta. AB - An increasing number of patients with osteogenesis imperfecta are undergoing pamidronate therapy to prevent the incidence of fragility fractures. The authors herein report a child aged 3 years who received five cycles of pamidronate, resulting in metaphyseal bands, known as "zebra lines." PMID- 20351993 TI - Case Report: Fibromatosis colli in a neonate. AB - Fibromatosis colli or pseudotumor of infancy of the sternocleidomastoid muscle is a rare cause of a benign neck mass in neonates and infants. If diagnosed correctly, it can be managed conservatively, and unnecessary investigations can be avoided. PMID- 20351994 TI - Ribbing disease. AB - Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc. PMID- 20351995 TI - Lipoma arborescens of the elbow. AB - Lipoma arborescens (LA) is a rare non-neoplastic intra-articular lesion that most commonly affects the knee joint, especially the suprapatellar bursa. It rarely affects the elbow joint. There are a few reports of involvement of the bicipital radial bursa. We report a case of LA, with characteristic MRI features, affecting the elbow joint in a young male. PMID- 20351996 TI - MRI in perianal fistulae. AB - MRI has become the method of choice for evaluating perianal fistulae due to its ability to display the anatomy of the sphincter muscles orthogonally, with good contrast resolution. In this article we give an outline of the classification of perianal fistulae and present a pictorial assay of sphincter anatomy and the MRI findings in perianal fistulae. This study is based on a retrospective analysis of 43 patients with a clinical diagnosis of perianal fistula. MRI revealed a total of 44 fistulae in 35 patients; eight patients had only perianal sinuses. PMID- 20351997 TI - CT mimics of peritoneal carcinomatosis. AB - Peritoneal carcinomatosis is a term used to describe widespread metastases of cancerous tumors in the peritoneal cavity. It is most common in carcinomas of the gastrointestinal tract (GIT) and ovaries, and must be considered to be the main diagnosis even when the primary is not known. A wide variety of disease processes mimic peritoneal carcinomatosis. Precise diagnosis based on imaging alone is often difficult and very often the final diagnosis is only obtained after appropriate histopathology or microbiology. PMID- 20351998 TI - Mesoaortic entrapment of a left inferior vena cava. AB - A persistent left inferior vena cava (IVC) is a rare anomaly, with a reported incidence of only 0.2-0.5%. When present, it courses between the superior mesenteric artery and the aorta to continue as the right IVC, similar to the course of a left renal vein (LRV). This anomaly is usually asymptomatic, but there may be vague abdominal complaints if the IVC is compressed in the mesoaortic angle. Although symptomatic compression of the LRV (anterior nutcracker syndrome) is well recognized, there has been only one report in the literature of a similar compression of a persistent left IVC. Because of its rarity, this anomaly may be missed or mistaken for other conditions on imaging. An accurate diagnosis is crucial as the presence of this anomaly may have implications for surgical treatment of aortic lesions or placement of an IVC filter. Magnetic resonance angiography and, more recently, multidetector computed tomography scan, can provide an exquisite three-dimensional demonstration of vascular abnormalities. PMID- 20351999 TI - Cavitatory mesenteric lymph node syndrome: A rare entity. AB - Celiac disease is a gluten sensitive enteropathy that involves an abnormal immunological response to glutens in wheat, rye etc. It predominantly involves the small intestinal mucosa, though, extra luminal manifestations can also occur. One rare extraluminal manifestation is cavitatory mesenteric lymph node syndrome. It occurs in refractory celiac disease and is associated with poor prognosis due to various complications. The diagnosis is often made on imaging when cystic mesenteric lymph nodes with fat-fluid levels are seen and this can then be confirmed by histopathological examination. We recently had a typical case where we were able to make this diagnosis. PMID- 20352000 TI - Paradoxical hepatic tumor: Undifferentiated embryonal sarcoma of the liver. AB - Undifferentiated embryonal sarcoma (UES) is a rare primary malignant tumor of the liver that typically presents in late childhood. We report a case of primary UES, which had a typical paradoxical appearance on different imaging modalities. PMID- 20352001 TI - Persistent mullerian duct syndrome. AB - Persistent Mullerian duct syndrome (PMDS) is a rare form of internal male pseudohermaphroditism in which Mullerian duct derivatives are seen in a male patient. This syndrome is characterized by the persistence of Mullerian duct derivatives (i.e. uterus, cervix, fallopian tubes and upper two thirds of vagina) in a phenotypically and karyotypically male patient. In this article we present the USG and MRI features of a case of PMDS with bilateral cryptorchidism and left sided inguinal hernia, containing the uterus and fallopian tubes. PMID- 20352002 TI - The economics of dialysis in India. PMID- 20352003 TI - Stroke in chronic kidney disease. AB - Chronic kidney disease (CKD) is associated with a higher risk for stroke in studies from developed countries. This prospective study was conducted to study the clinical profile, management, and outcome of stroke in patients of chronic kidney disease who had been admitted in our institute during the period from December 2004 to December 2006. A higher incidence of stroke was found in men and in the fifth decade of life. Hypertension and diabetes were found in 88.8 and 48.1% of the patients respectively. CKD was detected for the first time during stroke evaluation in 55.5% of the patients. Stroke was due to cerebral infarction in 48.14% and due to cerebral hemorrhage in 40.7% of the patients. Surgical intervention was needed in 14.8% of all patients while stroke was managed medically in the rest. Over 70% of the patients were discharged after they showed improvement in the symptoms. PMID- 20352004 TI - Determination of oxidative stress markers and their importance in early diagnosis of uremia-related complications. AB - The existence of oxidative stress and the higher incidence of cardiovascular diseases in association with uremia is well proved. The uremic status of serum copper, ceruloplasmin (CP), protein thiols, malonyldialdehyde (MDA), and glutathione S-transferase (GST) levels was studied. The study was carried out on 51 chronic renal failure (CRF) patients who were not on hemodialysis therapy and on 42 healthy controls. Serum urea, creatinine, and MDA levels were found to be significantly increased (P < 0.001), and total protein, albumin, protein thiols, and copper levels were found to be significantly decreased in CRF patients compared to normal controls (P < 0.001). Ceruloplasmin levels were decreased significantly (P < 0.05), and there was no significant change in serum GST levels in CRF patients compared to normal controls. In conclusion, the significant increase in levels of MDA, and the decrease in levels of protein thiols, CP, and copper in uremia patients when compared to controls, reconfirms the presence of stress in this patient population. In view of the changes in other markers of oxidative stress, this absence of any significant change in the activity of GST in uremia patients compared to controls, warrants further study. PMID- 20352005 TI - Carotid intima-media thickness in patients with end-stage renal disease. AB - Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure. PMID- 20352006 TI - Is carbon dioxide a safe and good alternative for diatrizoate meglumine as a contrast in digital subtraction angiography? AB - Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO(2)) can be used as an alternative contrast agent. The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO(2) using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO(2). 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO(2). Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 +/ 5.92 vs. 26.2 +/- 15.1 (P = 0.001), NAG: 1.63 +/- 0.90 vs. 3.6 +/- 2.14 (P = 0.0001), and AAP: 1.51 +/- 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO(2) group was GGT: 15.5 +/- 4.9 vs. 21.1 +/- 9.04 (P = 0.02), NAG: 2.12 +/- 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 +/- 0.76 vs. 2.51 +/- 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO(2). Images obtained with iodinated contrast were superior to those with CO(2,) however, the quality of image with CO(2) was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO(2) cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO(2). Quality of images is better with iodinated contrast. PMID- 20352007 TI - A rare association of emphysematous pyelonephritis with unrecognized diabetes and polycystic kidney. AB - Emphysematous pyelonephritis (EPN) is a rare, severe, gas-forming infection for which the treatment of choice is often an immediate nephrectomy, although many reports exist of conservative treatment of cases with antibiotic therapy and percutaneous drainage of abscesses. It usually occurs in diabetic patients and less frequently in subjects with an obstruction of the corresponding renoureteral unit; other predisposing factors are not common. We report here the case of a 51 year-old woman with a rare association of unrecognized diabetes and bilateral polycystic kidney disease who developed monolateral EPN. She had an emergency right nephrectomy and was admitted to Intensive Care Unit (ICU) for septic shock after surgery, requiring intensive resuscitation. The patient was managed with Coupled Plasma Filtration Adsorption (CPFA). Her clinical conditions rapidly improved and the hemofiltration was soon suspended. Urine and blood cultures were positive for the same Escherichia coli, which was susceptible to all tested antibiotics. The patient was transferred to the Nephrology Division and was discharged from the hospital without further dialysis after 34 days. This case report is somewhat unique because of the unusual association between undetected diabetes and polycystic kidney as predisposing factors of a severe infection of the urinary tract. PMID- 20352008 TI - Antenatal Bartter's syndrome with sensorineural deafness. AB - Bartter's syndrome is a group of inherited, salt-losing tubulopathies presenting as metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. We report here the first case of a neonate with bilateral, sensorineural deafness, a variant of antenatal Bartter's syndrome from an Indian community. PMID- 20352009 TI - Successful pregnancy in a chronically hemodialyzed patient with end-stage renal failure. AB - A 36 year-old female with chronic kidney failure due to hypertension and who was being treated with hemodialysis for eight months, was admitted to the hospital on the suspicion of being pregnant. Gynecological examination and ultrasound scan confirmed the pregnancy. Gestation was diagnosed in the 29(th) week after the patient felt fetal movements. Intensification of the dialysis treatment was started immediately after the diagnosis was made. PMID- 20352010 TI - Zygomycosis in a renal allograft recipient. AB - Invasive fungal infections can cause considerable morbidity and mortality in immunocompromised patients. Zygomycosis is a type of invasive fungal infection with a rapid course and grave prognosis. Renal transplant recipients with concomitant diabetes mellitus are most susceptible to this infection. We report here a case of disseminated zygomycosis (Rhizopus sp.) in a renal allograft recipient with posttransplant diabetes mellitus (PTDM). This is the first reported case of zygomycosis caused by Rhizopus species. PMID- 20352011 TI - 2, 8 Dihydroxyadenine urolithiasis: A case report and review of literature. AB - Adenine phosphoribosyl transferase deficiency is a rare metabolic abnormality presenting with 2,8 dihydroxyadenine urolithiasis. The stones are characteristically radiolucent and therefore need to be differentiated from uric acid stones which are also radiolucent and have identical chemical reactivity. No cases of 2, 8- dihydroxyadenine urolithiasis have been reported from India. We report a 3 year old child with 2, 8- dihydroxyadenine urolithiasis and acute renal failure. PMID- 20352012 TI - Renal arterial branch calcification mimicking renal calculi in ultrasonography. PMID- 20352013 TI - Reinforcement Learning and Savings Behavior. AB - We show that individual investors over-extrapolate from their personal experience when making savings decisions. Investors who experience particularly rewarding outcomes from saving in their 401(k)-a high average and/or low variance return increase their 401(k) savings rate more than investors who have less rewarding experiences with saving. This finding is not driven by aggregate time-series shocks, income effects, rational learning about investing skill, investor fixed effects, or time-varying investor-level heterogeneity that is correlated with portfolio allocations to stock, bond, and cash asset classes. We discuss implications for the equity premium puzzle and interventions aimed at improving household financial outcomes. PMID- 20352014 TI - The Beta-Binomial Distribution for Estimating the Number of False Rejections in Microarray Gene Expression Studies. AB - In differential expression analysis of microarray data, it is common to assume independence among null hypotheses (and thus gene expression levels). The independence assumption implies that the number of false rejections V follows a binomial distribution and leads to an estimator of the empirical false discovery rate (eFDR). The number of false rejections V is modeled with the beta-binomial distribution. An estimator of the beta-binomial false discovery rate (bbFDR) is then derived. This approach accounts for how the correlation among non differentially expressed genes influences the distribution of V. Permutations are used to generate the observed values for V under the null hypotheses and a beta binomial distribution is fit to the values of V. The bbFDR estimator is compared to the eFDR estimator in simulation studies of correlated non-differentially expressed genes and is found to outperform the eFDR for certain scenarios. As an example, this method is also used to perform an analysis that compares the gene expression of soft tissue sarcoma samples to normal tissue samples. PMID- 20352016 TI - ? AB - This work describes the bioethics situation in Nicaragua, with information on the circumstances and the context of activities in medical education and health care providers.The development of a new model of comprehensive health care-the implementation of health care policies that guarantee Nicaraguans better access to care and services free of charge, and the changes that have occurred in medical care, due in part to the growing recognition of greater patient autonomy and the increase in the use of new medical technologies-all have contributed in some part to current obstacles and dilemmas in medical clinics and between health care personnel.Bioethics in Nicaragua is in the initial stage of development. It is neither institutionalized nor is it subject to formal mechanisms that permit the resolution of complex ethical problems, thus presenting an important challenge for institutions of higher learning and decision-makers in health. PMID- 20352015 TI - Enhancing cellular cancer vaccines. AB - Various strategies have been used to generate cellular cancer vaccines with the expectation that they will become an effective part of the overall management of cancer patients. However, with few notable exceptions, immunization has not resulted in significant long-term therapeutic benefits. Tumor growth has continued and patient survival has been at best only modestly prolonged. One possible explanation is that as only a small proportion of the constituents of malignant cells are "tumor specific" and the vast majority are the products of nonantigenic, normal "housekeeping" genes, the immune response in patients immunized with cellular cancer vaccines is not sufficient to result in tumor rejection. Here, we review and characterize various types of cellular cancer vaccines. In addition, in a mouse breast cancer model system, we describe a unique strategy designed to enrich cellular vaccines for cells that induce tumor immunity. Numerous advantages and disadvantages of cancer immunotherapy with cellular vaccines are also presented. PMID- 20352018 TI - 5-HT(1A) Receptor Null Mutant Mice Responding Under a Differential-Reinforcement of-Low-Rate 72-Second Schedule of Reinforcement. AB - Over the last two decades, our ever-increasing ability to manipulate the mouse genome has resulted in a variety of genetically defined mouse models of depression and other psychiatric and neurological disorders. However, it is still the case that some relevant rodent models for depression and antidepressant action have been validated experimentally in rats only and not in mice. An important example of such models is the operant model of antidepressant action known as differential-reinforcement-of-low-rates 72-second (DRL 72-s). A specific set of drug-induced changes on the performance of rats responding under a DRL 72 s schedule of reinforcement has been shown to be a highly reliable predictor of antidepressant activity in human depressive disorders. The aim of this study is to validate the use of the DRL 72-s schedule in mice by both genetic and pharmacological means. We have analyzed the actions of the specific serotonin reuptake inhibitor (SSRI) fluoxetine and the tricyclic agent desipramine (DMI) on wild-type and 5-hydroxytryptamine 1A receptor-null mutant (5-HT(1A)R KO) mice. In agreement with the literature on rats, we found that fluoxetine produced an acute antidepressant-like effect in 5-HT(1A)R KO mice but not in wild-type (Wt) mice. Additionally, an antidepressant-like effect was observed when DMI was administered to both 5-HT(1A)R KO and Wt mice. In conclusion: through the use of both genetic and pharmacological strategies, this study validates the extension of a protocol involving the DRL 72-s operant schedule of reinforcement as a behavioral model for the action of antidepressants in mice. PMID- 20352019 TI - 'A'ole Drugs! Cultural Practices and Drug Resistance of Rural Hawaiian Youth. AB - This qualitative study examined how Native Hawaiian youth from rural communities utilized cultural practices to promote drug resistance and/or abstinence. Forty seven students from 5 different middle schools participated in gender specific focus groups that focused on the cultural and environmental contexts of drug use for Native Hawaiian youth. The findings described culturally specific activities that participants used in drug related problem situations. The findings also suggested that those youth with higher levels of enculturation were able to resist drugs more effectively than those youth who were disconnected from their culture. The implications of these findings for social work practice are discussed. PMID- 20352017 TI - Pathological interactions between hematopoietic stem cells and their niche revealed by mouse models of primary myelofibrosis. AB - Primary myelofibrosis (PMF) belongs to the Philadelphia-negative myeloproliferative neoplasms and is a hematological disorder caused by abnormal function of the hematopoietic stem cells. The disease manifests itself with a plethora of alterations, including anemia, splenomegaly and extramedullary hematopoiesis. Its hallmarks are progressive marrow fibrosis and atypical megakaryocytic hyperplasia, two distinctive features used to clinically monitor disease progression. In an attempt to investigate the role of abnormal megakaryocytopoiesis in the pathogenesis of PMF, several transgenic mouse models have been generated. These models are based either on mutations that interfere with the extrinsic (thrombopoietin and its receptor, MPL) and intrinsic (the GATA1 transcription factor) control of normal megakaryocytopoiesis, or on known genetic lesions associated with the human disease. Here we provide an up-to-date review on the insights into the pathobiology of human PMF achieved by studying these animal models, with particular emphasis on results obtained with Gata1(low) mice. PMID- 20352021 TI - Marital Transitions, Parenting, and Schooling: Exploring the Link Between Family Structure History and Adolescents' Academic Status. AB - The linkage between family structure and adolescents' academic experiences is part of a larger, dynamic process unfolding over time. To investigate this phenomenon, this study drew on the National Longitudinal Study of Adolescent Health and the Adolescent Health and Academic Achievement Study. Logistic regressions revealed that family structure at birth predicted students' academic status in math in the ninth grade, and multinomial regressions revealed that family instability, along with curricular location in the ninth grade, parenting behaviors, and adolescents' adjustment and aspirations, distinguished those who completed higher-level math by the end of high school from those who did not but still graduated from high school and from those who dropped out of high school. PMID- 20352022 TI - Single cell trapping in larger microwells capable of supporting cell spreading and proliferation. AB - Conventional cell trapping methods using microwells with small dimensions (10-20 MUm) are useful for examining the instantaneous cell response to reagents; however, such wells have insufficient space for longer duration screening tests that require observation of cell attachment and division. Here we describe a flow method that enables single cell trapping in microwells with dimensions of 50 MUm, a size sufficient to allow attachment and division of captured cells. Among various geometries tested, triangular microwells were found to be most efficient for single cell trapping while providing ample space for cells to grow and spread. An important trapping mechanism is the formation of fluid streamlines inside, rather than over, the microwells. A strong flow recirculation occurs in the triangular microwell so that it efficiently catches cells. Once a cell is captured, the cell presence in the microwell changes the flow pattern, thereby preventing trapping of other cells. About 62% of microwells were filled with single cells after a 20 min loading procedure. Human prostate cancer cells (PC3) were used for validation of our system. PMID- 20352023 TI - Oxidative stress in lens in vivo: inhibitory effect of caffeine. A preliminary report. AB - PURPOSE: Experiments have been conducted to study the hypothesis that caffeine would inhibit reactive oxygen species induced oxidative stress in the lens in vivo, with implications of attenuating or preventing cataract formation. METHODS: Oxidative stress was directly induced by administering 24% galactose diet to young adult rats. The treated group was fed a diet containing 24% galactose + 1% caffeine. Oxidative stress inflicted to the lens was assessed by measurement of glutathione (GSH) depletion and observing the status of lens clarity. RESULTS: Caffeine administration was found to minimize the loss of GSH. This was also associated with a better maintenance of lens transparency as compared to the untreated galactosemic group. CONCLUSIONS: The studies demonstrate that caffeine could be helpful in inhibiting oxidative stress in the lens with the consequence of attenuating cataract formation. PMID- 20352024 TI - Identification of crystallin modifications in the human lens cortex and nucleus using laser capture microdissection and CyDye labeling. AB - PURPOSE: With aging, lens crystallins undergo post-translational modifications (PTMs) and these modifications are believed to play a major role in age-related cataract development. The purpose of the present study was to determine the protein profiles of crystallins and their PTMs in the cortical and nuclear regions within an aging human lens to gain a better understanding about changes in crystallins as fiber cells migrate from cortical to nuclear region. METHODS: Laser capture microdissection (LCM) was used to select and capture cells from cortical and nuclear regions of 12 mum, optimum cutting temperature (OCT) compound-embedded frozen lens sections from a 69-year-old human lens. Proteins were extracted and then analyzed by 2-D difference gel electrophoresis (2-D DIGE) with sulfonated indocyanine dye (CyDye) labeling. Crystallin identities and their PTMs were then determined by Matrix-Assisted Laser Desorption/Ionization Time-of Flight (MALDI-TOF) and Electrospray Ionization Quadripole Linear Ion-Trap Liquid Chromatography (ESI-QTRAP LC-MS/MS) mass spectrometry. RESULTS: Crystallin fragments (M(r) <20 kDa) were present in both cortical and nuclear regions, while high molecular weight (HMW) aggregates (M(r) > 35 kDa) were mostly localized in the nuclear region. HMW complexes contained a relatively large number of truncated and modified beta-crystallins, compared to alpha- and gamma crystallins, and two lens-specific intermediate filaments, CP49 (phakinin) and filensin. Modified alpha-crystallins were in low abundance in the nuclear region compared to the cortical region. Several PTMs, including deamidation, oxidation, phosphorylation, ethylation, methylation, acetylation, and carbamylation, were identified in virtually all crystallins and CP49. The data provide the first report of human lens crystallin profiling by a combination of LCM, 2D-DIGE, and mass spectrometric analysis. CONCLUSIONS: The results suggested that as the fiber cells migrate from cortical region to the nuclear region, the crystallin degradation begins in the cortical region and continues in the nuclear region. However, a greater number of the HMW complexes exist mainly in the nuclear region. PMID- 20352025 TI - Smell perception in normal tension glaucoma patients. AB - PURPOSE: The aim of this study was to quantify the ability to identify odors in normal tension glaucoma (NTG) patients and healthy subjects with and without a primary vascular dysregulation (PVD). METHODS: Both self-assessment of smell perception and evaluation of odor identification by means of the 12-item odor identification test ("Sniffin' Sticks") were performed in the following groups of subjects: 1) 18 NTG patients with PVD (G+), 2) 18 NTG patients without PVD (G-), 3) 18 healthy subjects with PVD (H(+)) and 4) 18 healthy subjects without PVD (H ). The subjects self-assessment of smell perception was evaluated before the Sniffin' Sticks test by asking them to judge their ability to identify odors as either "average," "better than average," or "worse than average." RESULTS: Subjects with a PVD (G+ and H(+)) can identify odors significantly better than those without a PVD (G- and H-; in a score scale of 1-12 the score point difference=2.64, 95% CI=1.88-3.40, p<0.001). No significant differences in odor identification was found between NTG (groups G+ and G-) and healthy subjects (groups H(+) and H-; score point difference=-0.14, 95% CI=-0.9-0.62, p=0.72). CONCLUSIONS: Subjects with a PVD can identify odors significantly better than those without a PVD. PMID- 20352020 TI - Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review. AB - PROBLEM STATEMENT: Infection with retroviruses such as human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1) have been shown to lead to neurodegenerative diseases such as HIV-associated dementia (HAD) or neuroAIDS and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), respectively. APPROACH: HIV-1-induced neurologic disease is associated with an influx of HIV-infected monocytic cells across the blood-brain barrier. Following neuroinvasion, HIV-1 and viral proteins, in addition to cellular mediators released from infected and uninfected cells participate in astrocytic and neuronal dysregulation, leading to mild to severe neurocognitive disorders. RESULTS: The molecular architecture of viral regulatory components including the Long Terminal Repeat (LTR), genes encoding the viral proteins Tat, Vpr and Nef as well as the envelope gene encoding gp120 and gp41 have been implicated in 'indirect' mechanisms of neuronal injury, mechanisms which are likely responsible for the majority of CNS damage induced by HIV-1 infection. The neuropathogenesis of HAM/TSP is linked, in part, with both intra-and extracellular effectors functions of the viral transactivator protein Tax and likely other viral proteins. Tax is traditionally known to localize in the nucleus of infected cells serving as a regulator of both viral and cellular gene expression. CONCLUSION/RECOMMENDATIONS: However, recent evidence has suggested that Tax may also accumulate in the cytoplasm and be released from the infected cell through regulated cellular secretion processes. Once in the extracellular environment, Tax may cause functional alterations in cells of the peripheral blood, lymphoid organs and the central nervous system. These extracellular biological activities of Tax are likely very relevant to the neuropathogenesis of HTLV-1 and represent attractive targets for therapeutic intervention. PMID- 20352026 TI - Sequence variants of the DFNB31 gene among Usher syndrome patients of diverse origin. AB - PURPOSE: It has been demonstrated that mutations in deafness, autosomal recessive 31 (DFNB31), the gene encoding whirlin, is responsible for nonsyndromic hearing loss (NSHL; DFNB31) and Usher syndrome type II (USH2D). We screened DFNB31 in a large cohort of patients with different clinical subtypes of Usher syndrome (USH) to determine the prevalence of DFNB31 mutations among USH patients. METHODS: DFNB31 was screened in 149 USH2, 29 USH1, six atypical USH, and 11 unclassified USH patients from diverse ethnic backgrounds. Mutation detection was performed by direct sequencing of all coding exons. RESULTS: We identified 38 different variants among 195 patients. Most variants were clearly polymorphic, but at least two out of the 15 nonsynonymous variants (p.R350W and p.R882S) are predicted to impair whirlin structure and function, suggesting eventual pathogenicity. No putatively pathogenic mutation was found in the second allele of patients with these mutations. CONCLUSIONS: DFNB31 is not a major cause of USH. PMID- 20352027 TI - Dislocation of the elbow: a retrospective multicentre study of 86 patients. AB - The objective of this retrospective multicentre cohort study was to prospectively assess the long-term functional outcomes of simple and complex elbow dislocations.We analysed the hospital and outpatient records of 86 patients between 01.03.1999 and 25.02.2009 with an elbow dislocation. After a mean follow up of 3.3 years, all patients were re-examined at the outpatient clinic for measurement of different outcomes.The mean range of motion was ROM 135.5 degrees . The Mayo elbow performance index (MEPI) scored an average of 91.9 (87.5% of the patients were rated excellent or good). The average Quick disabilities of the arm, shoulder and hand (Quick- DASH) score was 9.7, the sports/music score 11.5 and work score 6.1. The Oxford function score was 75.7, Oxford pain score 75.2 and Oxford social-psychological score 73.9.Elbow dislocation is a mild disease and generally, the outcome is excellent. Functional results might improve with early active movements. PMID- 20352028 TI - Cellular Senescence is a Common Characteristic Shared by Preneoplasic and Osteo Arthritic Tissue. AB - OBJECTIVE: This study aims at highlighting the common signature between cartilaginous tissue in osteoarthritis (OA) and preneoplasic tissues preceding neoplasia and tumour formation and, second, focusing on the molecular mechanisms at the aetiology of both pathologies. RESULTS: Because age is the highest risk factor common for both OA and cancer development, it is tempting to compare the molecular mechanisms occurring at the onset of OA and preneoplasic lesions. Indeed, cellular senescence seems to be a common characteristic. Cellular senescence represents a natural barrier to suppress the unscheduled proliferation of damaged cells acting as a strong tumour suppressor pathway and in OA, it also occurs prematurely in chondrocytes. In this study, we review a number of molecular factors associated with the senescent phenotype. CONCLUSION: Whereas accumulation of senescent cells in preneoplasic-like lesions leads to tissue degeneration and potentially tumour development; in OA, senescent cells accumulate in a slowly proliferative tissue. This is likely contributing at reducing the risk of cell transformation. PMID- 20352029 TI - Candida Arthritis after Arthroscopic Arthroplasty in a Patient without Predisposing Factors. AB - Because candidiasis is usually associated with immunosuppression, candida arthritis in an immunocompetent patient is rare. The symptoms of candidiasis are similar to bacterial infections, tuberculosis, and autoimmune diseases. In our patient with no predisposing factors, candida arthritis was initially excluded because the probability of occurrence was low. The patient had no leukocytosis, the acid-fast bacteria (AFB) stain was negative, and the autoimmune antibody screen was negative. After Candida parapsilosis was cultured in the synovial fluid, the patient was treated with amphotericin B (0.7 mg/kg/day) and oral fluconazole (400 mg/day). The treatment was successful and there were no side effects of the medications. PMID- 20352030 TI - 'The average Scottish man has a cigarette hanging out of his mouth, lying there with a portion of chips': prospects for change in Scottish men's constructions of masculinity and their health-related beliefs and behaviours. AB - Men's apparent resistance to recommended health practices and their engagement with 'high-risk' behaviours has been associated with an increased risk of morbidity or mortality. Recent work has highlighted the need to think critically about the health-promoting behaviours that men appear reluctant to engage in, as well as examining those they embrace, and explore the gendered meanings that men attribute to their beliefs and behaviours. This article presents men's discussions of the 'practices of masculinity' and examines their relation to, and implications for, men's health-related behaviours as articulated in 15 focus group discussions (59 participants in total). The data capture both the experiences of men who felt pressured to engage in behaviours that may be harmful to their health in order to appear masculine and the accounts of those who regarded themselves as freer to embrace salutogenic health practices. Less is known about the circumstances that might encourage men to re-think their engagement in performances of masculinity that have potentially detrimental effects on their health. The data presented here suggest that ageing, illness, and fatherhood were some of the experiences that prompted men to re-evaluate their health practices. PMID- 20352031 TI - The Subjective Experience of Youth Psychotropic Treatment. AB - The psychotropic treatment of youth is increasing dramatically. This article examines child and adolescent psychopharmacological research and argues that social work practice and research must examine the complex relationships, social and psychological, in youth pharmacologic treatment. Regarding identity formation, this article explores the developmental consequences when youth adopt an illness narrative to make sense of everyday medication treatment. A conceptual framework for mapping the socio-cultural context of youth medication management is outlined. In the conclusion, youth psychotropic treatment is connected to a perplexing 'interpretive gap,' which highlights the subjective quality of medication treatment. PMID- 20352032 TI - Characterization of Red Tide Aerosol on the Texas Coast. AB - The Gulf of Mexico red tide, caused by the dinoflagellate Karenia brevis (= Gymnodinium breve), occurs almost annually and has adverse economic and health effects. Exposure of people to sea spray containing aerosolized brevetoxins (PbTxs, polyether brevetoxins produced by K. brevis) causes irritation of the eyes, nose, and throat. Anecdotal reports suggest that exposed individuals can experience respiratory irritation and exacerbation of existing respiratory illnesses. There has been no systematic study of human exposure to red tide aerosols. In the fall of 2000, during a red tide episode on the Gulf Coast near Corpus Christi, Texas, we sampled at the Marine Science Institute (MSI) at Port Aransas on 25 October. Between 26-27 October we sampled at the Texas State Aquarium (TSA) near Corpus Christi. Two Hi-Vol samplers equipped with a filter and a five-stage impactor gave low concentrations of PbTxs, requiring us to develop methods to improve the minimum detection limit. An LC/MS/MS technique was used combining an HPLC and the API 365 MS/MS. PbTx-2 and PbTx-3 were detected at the TSA sampling location; however, PbTx was not detected in the samples from the MSI. The concentration of PbTx-2 was 1.5-4.9 ng m(-3) but was much lower for PbTx 3. The ratio of PbTx-2 to PbTx-3 was 8.7 +/- 5.2. During the highest exposure period (26-27 October), PbTx-6 was also detected. No one reported respiratory symptoms at the MSI, whereas at the TSA, several field study workers reported symptoms including nose and throat irritation, and itchy skin. A high-volume impactor was used to aerodynamically classify the particles into different size fractions. PbTx-2 was detected in all samples taken at the TSA; however, PbTx-3 was detected only between 26-27 October when the PbTx concentration was high. The mass median aerodynamic diameter (MMAD) was 7-9 mm with a relatively narrow size range (geometric standard deviation [GSD] about 1.6). In this study, much lower airborne concentrations of PbTx, 1.6-6.7 ng m(-3) were reported, along with a few incidents of upper respiratory symptoms. Although the number of seven workers was too small for statistical analysis, the reported symptoms were consistent with no to low exposure at the MSI and detectable exposures at the TSA. This suggests that at lower environmental concentrations of about 2-7 ng m(-3),exposure to PbTx could result in upper respiratory symptoms. This is consistent with the particle size measurement. PMID- 20352034 TI - Breast Cancer Perceptions, Knowledge and Behavioral Practices among Women Living in a Rural Community. AB - We performed this study to assess women's perceptions, knowledge and behavioral practices for breast cancer prevention in a rural setting. A 61-item questionnaire was developed based on Health Belief Model constructs and completed by 185 women age 35 and older. Results showed significant differences in several areas including perceived susceptibility and severity. Overall knowledge was poor. In logistic regression perceived barriers and yearly clinical breast examination appeared to be significant predictors for regular screening behavior (OR=0.02, CI=0.03-0.09 and OR=0.23, CI=0.05-0.99, respectively). Behavioral interventions targeting barriers for rural women need to be designed to include consideration of specific barriers and clear information on the need for regular screening. PMID- 20352033 TI - Ethnic Differences in Adolescent Suicide in the United States. AB - Suicide is the third-leading cause of death for adolescents between 15 and 24 years of age in the United States and its rate has been increasing. Factors that contribute to rate of, risks for, or protection against depression and suicide may be different for people from cultures with different values and health beliefs. Although typically seen as affecting Caucasians more than other groups in the U.S., the rates of suicide among African Americans, Latinos, and others have been increasing. 87 studies were reviewed looking at rates for suicide/suicidal ideation, risk factors for suicide, protective factors/coping mechanisms, service delivery/barriers to care, and specific treatment or management of suicidal thoughts for adolescents from different ethnic groups in the U.S. The following ethnic groups in the U.S. were compared: African American, Latino, Asian American, Native American/Alaskan Native, and Hawaiian American. Although studies report conflicting rates, most studies still show an overall higher risk for suicidal behavior among Caucasian youth than any other group. Rates for suicidal behavior are growing for African American teens (perhaps more in boys), Latino teens (especially Latina girls), Asian American youth, Native American youth, Alaskan Native youth, and Hawaiian American youth. Details about these differences are discussed along with recommendations for clinicians working with youth at risk for suicide from minority cultures in the U.S. PMID- 20352035 TI - The Role of Coping and Race in Healthy Children's Experimental Pain Responses. AB - This study examined the relationship between race, laboratory-based coping strategies and anticipatory anxiety and pain intensity for cold, thermal (heat) and pressure experimental pain tasks. Participants were 123 healthy children and adolescents, including 33 African Americans (51% female; mean age =13.9 years) and 90 Caucasians (50% female; mean age = 12.6 years). Coping in response to the cold task was assessed with the Lab Coping Style interview; based on their interview responses, participants were categorized as 'attenders' (i.e., those who focused on the task) vs. 'distractors' (i.e., those who distracted themselves during the task). Analysis of covariance (ANCOVA) revealed significant interactions between race (African-American vs. Caucasian) and lab-based coping style after controlling for sex, age and socioeconomic status. African-American children classified as attenders reported less anticipatory anxiety for the cold task and lower pain intensity for the cold, heat and pressure tasks compared to those categorized as distractors. For these pain outcomes, Caucasian children classified as distractors reported less anticipatory anxiety and lower pain intensity relative to those categorized as attenders. The findings point to the moderating effect of coping in the relationship between race and experimental pain sensitivity. PMID- 20352036 TI - Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice. AB - PURPOSE: The DBA/2J (D2) mouse carries mutations in two of its genes, Tyrp1 and Gpnmb. These alterations result in the development of an immune response in the iris, leading to iris atrophy and pigment dispersion. The development of elevated intraocular pressure (IOP) in this model of glaucoma is considered to be a significant factor leading to the death of retinal ganglion cells (RGCs). Changes in gene expression in the retina have already been correlated with the appearance of elevated IOP in the D2 mouse. The purpose of the present study was to determine if any changes in gene expression occur prior to the development of IOP. METHODS: The IOP was measured monthly using a rebound tonometer in D2 and age-matched C57/BL6 (B6) mice (normal controls). D2 animals with normal IOP at 2 and 4 M were used. In addition, mice at the age of 6-7 M were included to look for any trends in gene expression that might develop during the progression of the disease. Separate RNA samples were prepared from each of three individual retinas for each age, and gene expression profiles were determined with the aid of mouse oligonucleotide arrays (Agilent). A subset of genes was examined with the aid of real-time PCR. Immunocytochemistry was used to visualize changes in the retina for some of the gene-products. RESULTS: Four hundred and thirteen oligonucleotide probes were differentially expressed in the retinas of 4 M versus 2 M old D2 mice. The most significantly up-regulated genes (181) were associated with immune responses including interferon signaling, the complement system and the antigen presentation pathway, whereas the down-regulated genes (232) were linked to pathways related to cell death and known neurological diseases/disorders. These particular changes were not revealed in the age-matched B6 mice. By 6 M, when IOP started to increase in many of the D2 mice, more robust changes of these same genes were observed. Changes in the levels of selected genes, representative of different functions/pathways, were validated with RT PCR, and changes in glial responses were visualized in the retina with immunocytochemistry. CONCLUSIONS: The results showed that the expression of genes related to the immune response and acute stress were altered independently of the development of elevated IOP, and indicated early involvement of the immune system in the onset of the disease. The later development of elevated IOP, observed in this animal model, was coincident with continued changes in expression of genes observed at earlier time points. Further studies are warranted to identify the roles of specific genes identified here with respect to the death of the RGCs. PMID- 20352037 TI - HIERARCHICAL SPATIAL MODELS FOR PREDICTING TREE SPECIES ASSEMBLAGES ACROSS LARGE DOMAINS. AB - Spatially explicit data layers of tree species assemblages, referred to as forest types or forest type groups, are a key component in large-scale assessments of forest sustainability, biodiversity, timber biomass, carbon sinks and forest health monitoring. This paper explores the utility of coupling georeferenced national forest inventory (NFI) data with readily available and spatially complete environmental predictor variables through spatially-varying multinomial logistic regression models to predict forest type groups across large forested landscapes. These models exploit underlying spatial associations within the NFI plot array and the spatially-varying impact of predictor variables to improve the accuracy of forest type group predictions. The richness of these models incurs onerous computational burdens and we discuss dimension reducing spatial processes that retain the richness in modeling. We illustrate using NFI data from Michigan, USA, where we provide a comprehensive analysis of this large study area and demonstrate improved prediction with associated measures of uncertainty. PMID- 20352038 TI - HDL as a contrast agent for medical imaging. AB - Contrast-enhanced MRI of atherosclerosis can provide valuable additional information on a patient's disease state. As a result of the interactions of HDL with atherosclerotic plaque and the flexibility of its reconstitution, it is a versatile candidate for the delivery of contrast-generating materials to this pathogenic lesion. We herein discuss the reports of HDL modified with gadolinium to act as an MRI contrast agent for atherosclerosis. Furthermore, HDL has been modified with fluorophores and nanocrystals, allowing it to act as a contrast agent for fluorescent imaging techniques and for computed tomography. Such modified HDL has been found to be macrophage specific, and, therefore, can provide macrophage density information via noninvasive MRI. As such, modified HDL is currently a valuable contrast agent for probing preclinical atherosclerosis. Future developments may allow the application of this particle to further diseases and pathological or physiological processes in both preclinical models as well as in patients. PMID- 20352039 TI - Structure and Receptor binding properties of a pandemic H1N1 virus hemagglutinin. AB - The 3D-structure of the major surface viral antigen from the recent H1N1 pandemic influenza virus (A/Darwin/2001/2009) was determined to 2.8 A resolution. The structure was used to analyze changes in the HA that have emerged during the first 11 months of the pandemic and have raised public health concerns. Receptor binding properties of this protein reveals a strict preference for human-type receptors. PMID- 20352042 TI - Regulatory T cell suppression of Gag-specific CD8 T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ART. AB - We tested the hypothesis that therapeutic vaccination against HIV-1 can increase the frequency and suppressive function of regulatory, CD4(+) T cells (Treg), thereby masking enhancement of HIV-1-specific CD8(+) T cell response. HIV-1 infected subjects on antiretroviral therapy (N = 17) enrolled in a phase I therapeutic vaccine trial received 2 doses of autologous dendritic cells (DC) loaded with HIV-1 peptides. The frequency of CD4(+)CD25(hi)FOXP3(+) Treg in blood was determined prior to and after vaccination in subjects and normal controls. Polyfunctional CD8(+) T cell responses were determined pre- and post-vaccine (N = 7) for 5 immune mediators after in vitro stimulation with Gag peptide, staphylococcal enterotoxin B (SEB), or medium alone. Total vaccine response (post vaccine-pre-vaccine) was compared in the Treg(+) and Treg-depleted (Treg-) sets. After vaccination, 12/17 subjects showed a trend of increased Treg frequency (P = 0.06) from 0.74% to 1.2%. The increased frequency did not correlate with CD8(+) T cell vaccine response by enzyme linked immunosorbent assay for interferon gamma production. Although there was no significant change in CD8(+) T cell polyfunctional response after vaccination, Treg depletion increased the polyfunctionality of the total vaccine response (P = 0.029), with a >2-fold increase in the percentage of CD8(+) T cells producing multiple immune mediators. In contrast, depletion of Treg did not enhance polyfunctional T cell response to SEB, implying specificity of suppression to HIV-1 Gag. Therapeutic immunization with a DC-based vaccine against HIV-1 caused a modest increase in Treg frequency and a significant increase in HIV-1-specific, Treg suppressive function. The Treg suppressive effect masked an increase in the vaccine-induced anti-HIV-1-specific polyfunctional response. The role of Treg should be considered in immunotherapeutic trials of HIV-1 infection. PMID- 20352043 TI - The outcome of health anxiety in primary care. A two-year follow-up study on health care costs and self-rated health. AB - BACKGROUND: Hypochondriasis is prevalent in primary care, but the diagnosis is hampered by its stigmatizing label and lack of valid diagnostic criteria. Recently, new empirically established criteria for Health anxiety were introduced. Little is known about Health anxiety's impact on longitudinal outcome, and this study aimed to examine impact on self-rated health and health care costs. METHODOLOGY/PRINCIPAL FINDINGS: 1785 consecutive primary care patients aged 18-65 consulting their family physicians (FPs) for a new illness were followed-up for two years. A stratified subsample of 701 patients was assessed by the Schedules for Clinical Assessment in Neuropsychiatry interview. Patients with mild (N = 21) and severe Health anxiety (N = 81) and Hypochondriasis according to the DSM-IV (N = 59) were compared with a comparison group of patients who had a well-defined medical condition according to their FPs and a low score on the screening questionnaire (N = 968). Self-rated health was measured by questionnaire at index and at three, 12, and 24 months, and health care use was extracted from patient registers. Compared with the 968 patients with well-defined medical conditions, the 81 severe Health anxiety patients and the 59 DSM-IV Hypochondriasis patients continued during follow-up to manifest significantly more Health anxiety (Whiteley-7 scale). They also continued to have significantly worse self-rated functioning related to physical and mental health (component scores of the SF-36). The severe Health anxiety patients used about 41 78% more health care per year in total, both during the 3 years preceding inclusion and during follow-up, whereas the DSM-IV Hypochondriasis patients did not have statistically significantly higher total use. A poor outcome of Health anxiety was not explained by comorbid depression, anxiety disorder or well defined medical condition. Patients with mild Health anxiety did not have a worse outcome on physical health and incurred significantly less health care costs than the group of patients with a well-defined medical condition. CONCLUSIONS/SIGNIFICANCE: Severe Health anxiety was found to be a disturbing and persistent condition. It is costly for the health care system and must be taken seriously, i.e. diagnosed and treated. This study supports the validity of recently introduced new criteria for Health anxiety. PMID- 20352044 TI - Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3 10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p.Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. CONCLUSIONS/SIGNIFICANCE: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype. PMID- 20352045 TI - The MinCDJ system in Bacillus subtilis prevents minicell formation by promoting divisome disassembly. AB - BACKGROUND: Cell division in Bacillus subtilis takes place precisely at midcell, through the action of Noc, which prevents division from occurring over the nucleoids, and the Min system, which prevents cell division from taking place at the poles. Originally it was thought that the Min system acts directly on FtsZ, preventing the formation of a Z-ring and, therefore, the formation of a complete cytokinetic ring at the poles. Recently, a new component of the B. subtilis Min system was identified, MinJ, which acts as a bridge between DivIVA and MinCD. METHODOLOGY/PRINCIPAL FINDINGS: We used fluorescence microscopy and molecular genetics to examine the molecular role of MinJ. We found that in the absence of a functional Min system, FtsA, FtsL and PBP-2B remain associated with completed division sites. Evidence is provided that MinCDJ are responsible for the failure of these proteins to localize properly, indicating that MinCDJ can act on membrane integral components of the divisome. CONCLUSIONS/SIGNIFICANCE: Taken together, we postulate that the main function of the Min system is to prevent minicell formation adjacent to recently completed division sites by promoting the disassembly of the cytokinetic ring, thereby ensuring that cell division occurs only once per cell cycle. Thus, the role of the Min system in rod-shaped bacteria seems not to be restricted to an inhibitory function on FtsZ polymerization, but can act on different levels of the divisome. PMID- 20352046 TI - Distinct and histone-specific modifications mediate positive versus negative transcriptional regulation of TSHalpha promoter. AB - BACKGROUND: Hormonally-regulated histone modifications that govern positive versus negative transcription of target genes are poorly characterized despite their importance for normal and pathological endocrine function. There have been only a few studies examining chromatin modifications on target gene promoters by nuclear hormone receptors. Moreover, these studies have focused on positively regulated target genes. TSHalpha, a heterodimer partner for thyrotropin (TSH), is secreted by the pituitary gland. T(3) negatively regulates TSHalpha gene expression via thyroid hormone receptors (TRs) which belong to the nuclear hormone receptor superfamily, whereas thyrotropin releasing hormone (TRH) positively regulates via the TRH receptor, a G protein-coupled receptor. METHODOLOGY/PRINCIPAL FINDINGS: We studied regulation of the TSHalpha gene by cAMP and T(3) using chromatin immunoprecipitation (ChIP) assays in stably transfected rat pituitary cells containing the human TSHalpha promoter. Interestingly, cAMP selectively increased histone H4 acetylation whereas, as previously reported, T(3) induced histone H3 acetylation. In particular, cAMP increased H4K5 and H4K8 acetylation and decreased H4K20 trimethylation, modifications associated with transcriptional activation. T(3) increased H3K9 and H3K18 acetylation and H3K4 trimethylation; however, it also decreased H3K27 acetylation and increased H3K27 trimethylation which are associated with transcriptional repression. Of note, cAMP recruited pCREB, CBP/p300, and PCAF to the promoter whereas T(3) caused dissociation of NCoR/SMRT and HDAC3. Overexpression of a dominant negative mutant thyroid hormone receptor (TR) from a patient with resistance to thyroid hormone (RTH) led to less T(3)-dependent negative regulation and partially blocked histone H3 modifications of the TSHalpha promoter. CONCLUSIONS/SIGNIFICANCE: Our findings show that non overlapping and specific histone modifications determine positive versus negative transcriptional regulation, and integrate opposing hormonal and intracellular signals at the TSHalpha promoter. A mutant TR from a patient with RTH exerted dominant negative activity by blocking the histone modifications induced by T(3) on the TSHalpha promoter and likely contributes to the inappropriate TSH production observed in RTH. PMID- 20352047 TI - Ozz-E3 ubiquitin ligase targets sarcomeric embryonic myosin heavy chain during muscle development. AB - Muscle contractile proteins are expressed as a series of developmental isoforms that are in constant dynamic remodeling during embryogenesis, but how obsolete molecules are recognized and removed is not known. Ozz is a developmentally regulated protein that functions as the adaptor component of a RING-type ubiquitin ligase complex specific to striated muscle. Ozz(-/-) mutants exhibit defects in myofibrillogenesis and myofiber differentiation. Here we show that Ozz targets the rod portion of embryonic myosin heavy chain and preferentially recognizes the sarcomeric rather than the soluble pool of myosin. We present evidence that Ozz binding to the embryonic myosin isoform within sarcomeric thick filaments marks it for ubiquitination and proteolytic degradation, allowing its replacement with neonatal or adult isoforms. This unique function positions Ozz within a system that facilitates sarcomeric myosin remodeling during muscle maturation and regeneration. Our findings identify Ozz-E3 as the ubiquitin ligase complex that interacts with and regulates myosin within its fully assembled cytoskeletal structure. PMID- 20352048 TI - Citability of original research and reviews in journals and their sponsored supplements. AB - BACKGROUND: The contents of pharmaceutical industry sponsored supplements to medical journals are perceived to be less credible than the contents of their parent journals. It is unknown if their contents are cited as often. The objective of this study was to quantify the citability of original research and reviews contained in supplements and compare it with that for the parent journal. METHODOLOGY/PRINCIPAL FINDINGS: This was a cohort study of 446 articles published in the Journal of Clinical Psychiatry (JCP) and its supplements for calendar years 2000 and 2005. The total citation counts for each article up to October 5, 2009 were retrieved from the ISI Web of Science database. The main outcome measure was the number of citations received by an article since publication. Regular journal articles included 114 from calendar year 2000 and 190 from 2005. Articles from supplements included 90 from 2000 and 52 from 2005. The median citation counts for the 3 years post-publication were 10 (interquartile range [IQR], 4-20), 14 (IQR, 8-20), 13.5 (IQR, 8-23), and 13.5 (IQR, 8-20), for the 2000 parent journal, 2000 supplements, 2005 parent journal, and 2005 supplements, respectively. Citation counts were higher for the articles in the supplements than the parent journal for the cohorts from 2000 (p = .02), and no different for the year 2005 cohorts (p = .88). The 2005 parent journal cohort had higher citation counts than the 2000 cohort (p = .007), in contrast to the supplements where citation counts remained the same (p = .94). CONCLUSIONS/SIGNIFICANCE: Articles published in JCP supplements are robustly cited and thus can be influential in guiding clinical and research practice, as well as shaping critical thinking. Because they are printed under the sponsorship of commercial interests, they may be perceived as less than objective. A reasonable step to help improve this perception would be to ensure that supplements are peer reviewed in the same way as regular articles in the parent journal. PMID- 20352049 TI - Differential expression of the circadian clock in maternal and embryonic tissues of mice. AB - BACKGROUND: Molecular feedback loops involving transcription and translation and several key genes are at the core of circadian regulatory cycles affecting cellular pathways and metabolism. These cycles are active in most adult animal cells but little is known about their expression or influence during development. METHODOLOGY/PRINCIPAL FINDINGS: To determine if circadian cycles are active during mammalian development we measured the expression of key circadian genes during embryogenesis in mice using quantitative real-time RT-PCR. All of the genes examined were expressed in whole embryos beginning at the earliest age examined, embryonic day 10. In contrast to adult tissues, circadian variation was absent for all genes at all of the embryonic ages examined in either whole embryos or individual tissues. Using a bioluminescent fusion protein that tracks translation of the circadian gene, per2, we also analyzed protein levels. Similar to mRNA, a protein rhythm was observed in adult tissue but not in embryonic tissues collected in-vivo. In contrast, when tissues were placed in culture for the continuous assay of bioluminescence, rhythms were observed in embryonic (E18) tissues. We found that placing embryonic tissues in culture set the timing (phase) of these rhythms, suggesting the importance of a synchronizing signal for the expression of circadian cycles in developing tissues. CONCLUSIONS/SIGNIFICANCE: These results show that embryonic tissues express key circadian genes and have the capacity to express active circadian regulatory cycles. In vivo, circadian cycles are not expressed in embryonic tissues as they are in adult tissues. Individual cells might express oscillations, but are not synchronized until later in development. PMID- 20352050 TI - Gauging U.S. Emergency Medical Services workers' willingness to respond to pandemic influenza using a threat- and efficacy-based assessment framework. AB - BACKGROUND: Emergency Medical Services workers' willingness to report to duty in an influenza pandemic is essential to healthcare system surge amidst a global threat. Application of Witte's Extended Parallel Process Model (EPPM) has shown utility for revealing influences of perceived threat and efficacy on non-EMS public health providers' willingness to respond in an influenza pandemic. We thus propose using an EPPM-informed assessment of EMS workers' perspectives toward fulfilling their influenza pandemic response roles. METHODOLOGY/PRINCIPAL FINDINGS: We administered an EPPM-informed snapshot survey about attitudes and beliefs toward pandemic influenza response, to a nationally representative, stratified random sample of 1,537 U.S. EMS workers from May-June 2009 (overall response rate: 49%). Of the 586 respondents who met inclusion criteria (currently active EMS providers in primarily EMS response roles), 12% indicated they would not voluntarily report to duty in a pandemic influenza emergency if asked, 7% if required. A majority (52%) indicated their unwillingness to report to work if risk of disease transmission to family existed. Confidence in personal safety at work (OR = 3.3) and a high threat/high efficacy ("concerned and confident") EPPM profile (OR = 4.7) distinguished those who were more likely to voluntarily report to duty. Although 96% of EMS workers indicated that they would probably or definitely report to work if they were guaranteed a pandemic influenza vaccine, only 59% had received an influenza immunization in the preceding 12 months. CONCLUSIONS/SIGNIFICANCE: EMS workers' response willingness gaps pose a substantial challenge to prehospital surge capacity in an influenza pandemic. "Concerned and confident" EMS workers are more than four times as likely to fulfill pandemic influenza response expectations. Confidence in workplace safety is a positively influential modifier of their response willingness. These findings can inform insights into interventions for enhancing EMS workers' willingness to respond in the face of a global infectious disease threat. PMID- 20352051 TI - Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. AB - Duplication of the centrosome is well controlled during faithful cell division while deregulation of this process leads to supernumary centrosomes, chromosome missegregation and aneuploidy, a hallmark of many cancer cells. We previously reported that Polo-like kinase 2 (Plk2) is activated near the G1/S phase transition, and regulates the reproduction of centrosomes. In search for Plk2 interacting proteins we have identified NPM/B23 (Nucleophosmin) as a novel Plk2 binding partner. We find that Plk2 and NPM/B23 interact in vitro in a Polo-box dependent manner. An association between both proteins was also observed in vivo. Moreover, we show that Plk2 phosphorylates NPM/B23 on serine 4 in vivo in S phase. Notably, expression of a non-phosphorylatable NPM/B23 S4A mutant interferes with centriole reduplication in S-phase arrested cells and leads to a dilution of centriole numbers in unperturbed U2OS cells. The corresponding phospho-mimicking mutants have the opposite effect and their expression leads to the accumulation of centrioles. These findings suggest that NPM/B23 is a direct target of Plk2 in the regulation of centriole duplication and that phosphorylation on serine 4 can trigger this process. PMID- 20352053 TI - Fairy Tales: Attraction and Stereotypes in Same-Gender Relationships. AB - We examine the process of romantic attraction in same-gender relationships using open and closed-ended questionnaire data from a sample of 120 men and women in Northern California. Agreeableness (e.g., kind, supportive) and Extraversion (e.g., fun, sense of humor) are the two most prominent bases of attraction, followed by Physical Attractiveness (e.g., appearance, sexy). The least important attractors represent traits associated with material success (e.g., financially secure, nice house). We also find evidence of seemingly contradictory attraction processes documented previously in heterosexual romantic relationships, in which individuals become disillusioned with the qualities in a partner that were initially appealing. Our findings challenge common stereotypes of same-gender relationships. The results document broad similarities between same-gender and cross-gender couples in attraction. PMID- 20352052 TI - Cloning and characterisation of Schistosoma japonicum insulin receptors. AB - BACKGROUND: Schistosomes depend for growth and development on host hormonal signals, which may include the insulin signalling pathway. We cloned and assessed the function of two insulin receptors from Schistosoma japonicum in order to shed light on their role in schistosome biology. METHODOLOGY/PRINCIPAL FINDINGS: We isolated, from S. japonicum, insulin receptors 1 (SjIR-1) and 2 (SjIR-2) sharing close sequence identity to their S. mansoni homologues (SmIR-1 and SmIR-2). SjIR 1 is located on the tegument basal membrane and the internal epithelium of adult worms, whereas SjIR-2 is located in the parenchyma of males and the vitelline tissue of females. Phylogenetic analysis showed that SjIR-2 and SmIR-2 are close to Echinococcus multilocularis insulin receptor (EmIR), suggesting that SjIR-2, SmIR-2 and EmIR share similar roles in growth and development in the three taxa. Structure homology modelling recovered the conserved structure between the SjIRs and Homo sapiens IR (HIR) implying a common predicted binding mechanism in the ligand domain and the same downstream signal transduction processing in the tyrosine kinase domain as in HIR. Two-hybrid analysis was used to confirm that the ligand domains of SjIR-1 and SjIR-2 contain the insulin binding site. Incubation of adult worms in vitro, both with a specific insulin receptor inhibitor and anti-SjIRs antibodies, resulted in a significant decrease in worm glucose levels, suggesting again the same function for SjIRs in regulating glucose uptake as described for mammalian cells. CONCLUSIONS: Adult worms of S. japonicum possess insulin receptors that can specifically bind to insulin, indicating that the parasite can utilize host insulin for development and growth by sharing the same pathway as mammalian cells in regulating glucose uptake. A complete understanding of the role of SjIRs in the biology of S. japonicum may result in their use as new targets for drug and vaccine development against schistosomiasis. PMID- 20352054 TI - A Brief Review on How Pregnancy and Sex Hormones Interfere with Taste and Food Intake. AB - Many physiological and behavioral changes take place during pregnancy, including changes in taste and an increase in food intake. These changes are necessary to ensure growth and development of a healthy fetus. Both hyperphagia and taste changes during pregnancy may be induced by sex hormones estrogen and progesterone that are increased during pregnancy. Indeed, it has been shown that estrogen decreases food intake, while progesterone increases food intake. This is for instance apparent from the fact that food intake changes during the menstrual cycle with variation in sex hormones. This review will give a short overview of the effects of pregnancy and sex hormones on food intake and taste. PMID- 20352056 TI - Strategies in Forecasting Outcomes in Ethical Decision-making: Identifying and Analyzing the Causes of the Problem. AB - This study examined the role of key causal analysis strategies in forecasting and ethical decision-making. Undergraduate participants took on the role of the key actor in several ethical problems and were asked to identify and analyze the causes, forecast potential outcomes, and make a decision about each problem. Time pressure and analytic mindset were manipulated while participants worked through these problems. The results indicated that forecast quality was associated with decision ethicality, and the identification of the critical causes of the problem was associated with both higher quality forecasts and higher ethicality of decisions. Neither time pressure nor analytic mindset impacted forecasts or ethicality of decisions. Theoretical and practical implications of these findings are discussed. PMID- 20352055 TI - Gold-catalyzed Intermolecular [4C + 3C] Cycloaddition Reactions. AB - In the presence of the N-heterocyclic carbene gold catalyst (NHC-AuIPr, 7), propargyl esters 1a-f and 13 undergo a [4C + 3C] cycloaddition reaction with cyclopentadiene and furan under mild conditions. The evidence suggests the formation of the seven-membered ring occurs by a direct cycloaddition process, rather than a stepwise cyclopropanation/Cope rearrangement sequence. PMID- 20352057 TI - A New Crosslinkable Oxygen Sensor Covalently Bonded into Poly(2-hydroxyethyl methacrylate)-CO-Polyacrylamide Thin Film for Dissolved Oxygen Sensing. AB - A new oxygen sensor, compound 2, was synthesized through a chemical modification of a popularly used oxygen sensor of platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6 pentafluorophenyl)-porphyrin (PtTFPP). The new sensor compound 2 possesses four crosslinkable methacrylate functional moieties, enabling it to be polymerized and crosslinked with other monomers for polymer sensing film (also called membrane) preparation. Using this characteristic, compound 2 was covalently bonded to hydrophilic poly(2-hydroxyethyl methacrylate)-co-polyacrylamide (referred to as PHEMA to simplify) and hydrophobic polystyrene (PS) films. To better understand the advantages and disadvantages of chemical crosslinking approaches and the influence of polymer matrices on sensing performance, PtTFPP was physically incorporated into the same PHEMA and PS matrices to compare. Response to dissolved oxygen (DO), leaching of the sensor molecules from their matrices, photostability of the sensors, and response time to DO changes were studied. It was concluded that the chemical crosslinking of the sensor compound 2 in polymer matrices: (i) alleviated the leaching problem of sensor molecules which usually occurred in the physically doped sensing systems and (ii) significantly improved sensors' photostability. The PHEMA matrix was demonstrated to be more suitable for oxygen sensing than PS, because for the same sensor molecule, the oxygen sensitivity in PHEMA film was higher than that in PS and response time to DO change in the PHEMA film was faster than that in PS. It was the first time oxygen sensing films were successfully prepared using biocompatible hydrophilic PHEMA as a matrix, which does not allow leaching of the sensor molecules from the polymer matrix, has a faster response to DO changes than that of PS, and does not present cytotoxicity to human lung adenocarcinoma epithelial cells (A549). It is expected that the new sensor compound 2 and its similar compounds with chemically crosslinking characteristics can be widely applied to generate many interesting oxygen sensing materials for studying biological phenomena. PMID- 20352058 TI - Design of a Catheter-Based Device for Performing Percutaneous Chordal-Cutting Procedures. AB - This paper focuses on the design and implementation of a percutaneous catheter based device to provide physicians with an externally controlled tool capable of manipulating and cutting specific chordae tendinae within the hear to alleviate problems associated with some forms of mitral valve regurgitationt. In the United States alone, approximately 500,000 people develop ischemic or functional MR per year, and the chordae tendinae cutting procedure and device are needed because many patients do not have the required level of health necessary to survive open heart surgery. A deterministic design process was used to generate several design concepts and then evaluate and compare each concept based on a set of functional requirements. A final concept to be alpha prototyped was then chosen, further developed, and fabricated. Experiments showed that the design was capable of locating and grabbing a chord and that ultrasound imaging is a viable method for navigating the device inside of the human body. Once contact between the chord and an RF ablator tip was confirmed, the chord was successfully ablated. PMID- 20352059 TI - Highly aspherical silica nanoshells by templating tubular liposomes. AB - A dual-lipid liposome system consisting of a phospholipid and a skin ceramide extruded though a 100 nm membrane yields novel tubular and helical liposomes. These liposomes were used as templates to generate highly aspherical silica nanocapsules with length to diameter aspect ratios exceeding 10. Many of these nanocapsules have the morphology of a bulbous end attached to a long tip, mimicking microneedles attached to a reservoir. The fidelity of helical liposomes is transcribed to the silicas and the long tips indicate helically entwined left handed silica structures. The silica coating is expected to protect and stabilize the internal contents of the liposomes, as well as enable surface functionalization for applications in drug or targeted delivery. PMID- 20352060 TI - Akt signaling in platelets and thrombosis. AB - Akt is a Ser-Thr kinase with pleiotropic effects on cell survival, growth and metabolism. Recent evidence from gene-deletion studies in mice, and analysis of human platelets treated with Akt inhibitors, suggest that Akt regulates platelet activation, with potential consequences for thrombosis. Akt activation is regulated by the level of phosphoinositide 3-phosphates, and proteins that regulate concentrations of this lipid also regulate Akt activation and platelet function. Although the effectors through which Akt contributes to platelet activation are not definitively known, several candidates are discussed, including endothelial nitric oxide synthase, glycogen synthase kinase 3beta, phosphodiesterase 3A and the integrin beta(3) tail. Selective inhibitors of Akt isoforms or of proteins that contribute to its activation, such as individual PI3K isoforms, may make attractive targets for antithrombotic therapy. This review summarizes the current literature describing Akt activity and its regulation in platelets, including speculation regarding the future of Akt or its regulatory pathways as targets for the development of antithrombotic therapies. PMID- 20352061 TI - Fluctuations and interactions of semi-flexible polyelectrolytes in columnar assemblies. AB - We have developed a statistical theory for columnar aggregates of semi-flexible polyelectrolytes. The applicability of previous, simplified theories was limited to polyelectrolytes with unrealistically high effective charge and, hence, with strongly suppressed thermal undulations. To avoid this problem, we utilized more consistent approximations for short-range image-charge forces and steric confinement, resulting in new predictions for polyelectrolytes with more practically important, lower effective linear charge densities. In the present paper, we focus on aggregates of wormlike chains with uniform surface charge density, although the same basic ideas may also be applied to structured polyelectrolytes. We find that undulations effectively extend the range of electrostatic interactions between polyelectrolytes upon decreasing aggregate density, in qualitative agreement with previous theories. However, in contrast to previous theories, we demonstrate that steric confinement provides the dominant rather than a negligible contribution at higher aggregate densities and significant quantitative corrections at lower densities, resulting in osmotic pressure isotherms that drastically differ from previous predictions. PMID- 20352062 TI - Analytic Derivation and Monte Carlo Validation of a Sensitivity Formula for Slit Slit Collimation With Penetration. AB - A slit-slit collimator consists of two orthogonal slits and can be conceptualized as a generalized pinhole. Since the two slits are independent of each other, there can be independent axial and transaxial acceptance angles. A small axial acceptance angle may help mitigate axial blurring with circular orbits, allowing multiple copies axially. In addition, since the two slit planes can be placed at different distances with respect to the source, a better detector usage can be achieved, especially in the case of detectors and imaged objects with different aspect ratios. In this paper an analytical expression is derived for the sensitivity of slit-slit collimation including effective slit widths for photon penetration. An analytical expression for sensitivity is necessary in order to accurately model the system response. This expression could also be useful for comparing the slit-slit's sensitivity performance with others. When the effective slit width is used instead of the geometric slit width, the derived analytical expression accurately accounts for photon penetration of the aperture. The derived expression for the sensitivity was validated by Monte Carlo simulation for both geometric and penetrative cases. PMID- 20352063 TI - EXPLORATION OF BRAVERMAN REACTION CHEMISTRY. SYNTHESIS OF TRICYCLIC DIHYDROTHIOPHENE DIOXIDE DERIVATIVES FROM BISPROPARGYL SULFONES. AB - The base-mediated bicyclization of unsymmetrical bispropargyl sulfones furnishes varying yields of dihydroisobenzothiophene dioxides through a presumed diradical intermediate. Attempts to trap a putative thiophene dioxide intermediate via Diels-Alder reaction with a pendant alkyne were not successful. PMID- 20352065 TI - Equivalence of Family Functioning and Externalizing in Adolescent Substance Users of Different Race/Ethnicity. AB - Brief Strategic Family Therapy (BSFT) for Adolescent Drug Abuse clinical trial of 480 adolescents boys and girls age 12 to 17 and their parents was designed to maximize the chance that a sufficient number of Hispanic and Black adolescents would be included to allow valid subgroup comparisons. Examination of measurement invariance is an important step to ensure valid analysis. Two construct areas important to the analysis of trial results, adolescent problem behaviors and family functioning showed a high degree of measurement invariance, which allowed valid comparisons of mean baseline differences across groups. Results showed that Black families had significantly higher initial levels of family functioning and lower levels of adolescent externalizing than either Hispanic or White non Hispanic families. This pattern is consistent with an increased likelihood of referral of Black adolescents with more severe problems to restricted setting rather than to outpatient drug abuse treatment. This possibility highlights the importance of considering differing baseline characteristics of subgroups prior to assessing differential treatment effectiveness to prevent confounding. PMID- 20352064 TI - CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PMID- 20352066 TI - Biodurability of Single-Walled Carbon Nanotubes Depends on Surface Functionalization. AB - Recent research has led to increased concern about the potential adverse human health impacts of carbon nanotubes, and further work is needed to better characterize those risks and develop risk management strategies. One of the most important determinants of the chronic pathogenic potential of a respirable fiber is its biological durability, which affects the long-term dose retained in the lungs, or biopersistence. The present article characterizes the biodurability of single-walled carbon nanotubes using an in vitro assay simulating the phagolysosome. Biodurability is observed to depend on the chemistry of nanotube surface functionalization. Single-walled nanotubes with carboxylated surfaces are unique in their ability to undergo 90-day degradation in a phagolysosomal simulant leading to length reduction and accumulation of ultrafine solid carbonaceous debris. Unmodified, ozone-treated, and aryl-sulfonated tubes do not degrade under these conditions. We attribute the difference to the unique chemistry of acid carboxylation, which not only introduces COOH surface groups, but also causes collateral damage to the tubular graphenic backbone in the form of neighboring active sites that provide points of attack for further oxidative degradation. These results suggest the strategic use of surface carboxylation in nanotube applications where biodegradation may improve safety or add function. PMID- 20352067 TI - Novel Pharmacologic Approaches for the Management of Diabetic Retinopathy. AB - Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy. PMID- 20352068 TI - Cobalt - poly(amido amine) superparamagnetic nanocomposites. AB - Metallic cobalt-dendrimer nanocomposites were prepared using generation 5 Poly(amido amine) dendrimers with primary amino termini. Cobalt loading of ~38 atoms per dendrimer was determined by atomic absorption spectrophotometry. Magnetic properties of the cobalt-dendrimer nanocomposites were investigated across the temperature range from 2-300 K by SQUID magnetometry. Magnetization as a function of temperature and applied field strength was studied in zero field cooled samples. Magnetization-demagnetization curves (hysteresis loops) were also acquired at temperatures between 10 - 300 K. These results clearly indicate superparamagnetism for the nanocomposites with a characteristic blocking temperature of ~50 K. PMID- 20352069 TI - Screening for Learning and Memory Mutations: A New Approach. AB - We describe a fully automated, live-in 24/7 test environment, with experimental protocols that measure the accuracy and precision with which mice match the ratio of their expected visit durations to the ratio of the incomes obtained from two hoppers, the progress of instrumental and classical conditioning (trials-to acquisition), the accuracy and precision of interval timing, the effect of relative probability on the choice of a timed departure target, and the accuracy and precision of memory for the times of day at which food is available. The system is compact; it obviates the handling of the mice during testing; it requires negligible amounts of experimenter/technician time; and it delivers clear and extensive results from 3 protocols within a total of 7-9 days after the mice are placed in the test environment. Only a single 24-hour period is required for the completion of first protocol (the matching protocol), which is strong test of temporal and spatial estimation and memory mechanisms. Thus, the system permits the extensive screening of many mice in a short period of time and in limited space. The software is publicly available. PMID- 20352070 TI - Adjusting for Health Status in Non-Linear Models of Health Care Disparities. AB - This article compared conceptual and empirical strengths of alternative methods for estimating racial disparities using non-linear models of health care access. Three methods were presented (propensity score, rank and replace, and a combined method) that adjust for health status while allowing SES variables to mediate the relationship between race and access to care. Applying these methods to a nationally representative sample of blacks and non-Hispanic whites surveyed in the 2003 and 2004 Medical Expenditure Panel Surveys (MEPS), we assessed the concordance of each of these methods with the Institute of Medicine (IOM) definition of racial disparities, and empirically compared the methods' predicted disparity estimates, the variance of the estimates, and the sensitivity of the estimates to limitations of available data. The rank and replace and combined methods (but not the propensity score method) are concordant with the IOM definition of racial disparities in that each creates a comparison group with the appropriate marginal distributions of health status and SES variables. Predicted disparities and prediction variances were similar for the rank and replace and combined methods, but the rank and replace method was sensitive to limitations on SES information. For all methods, limiting health status information significantly reduced estimates of disparities compared to a more comprehensive dataset. We conclude that the two IOM-concordant methods were similar enough that either could be considered in disparity predictions. In datasets with limited SES information, the combined method is the better choice. PMID- 20352071 TI - Evolution of the Bifunctional Lead MU Agonist / delta Antagonist Containing the Dmt-Tic Opioid Pharmacophore. AB - Based on a renewed importance recently attributed to bi- or multifunctional opioids, we report the synthesis and pharmacological evaluation of some analogues derived from our lead MU agonist / delta antagonist, H-Dmt-Tic-Gly-NH-Bzl. Our previous studies focused on the importance of the C-teminal benzyl function in the induction of such bifunctional activity. The introduction of some substituents in the para position of the phenyl ring (-Cl, -CH(3), partially NO(2), inactive -NH(2)) was found to give a more potent MU agonist / antagonist effect associated with a relatively unmodified delta antagonist activity (pA(2) = 8.28-9.02). Increasing the steric hindrance of the benzyl group (using diphenylmethyl and tetrahydroisoquinoline functionalities) substantially maintained the MU agonist and delta antagonist activities of the lead compound. Finally and quite unexpectedly D-Tic2, considered as a wrong opioid message now; inserted into the reference compound in lieu of L-Tic, provided a MU agonist / delta agonist better than our reference ligand (H-Dmt-Tic-Gly-NH-Ph) and was endowed with the same pharmacological profile. PMID- 20352072 TI - Oral Fat Exposure Pattern and Lipid Loading Effects on the Serum Triacylglycerol Concentration of Humans. AB - Orosensory exposure to dietary fat elicits an early, transient spike (first phase; minutes 0-60) and augmented, more sustained postprandial (second phase; minutes 120-360) elevation of serum triacylglycerol (TAG) in humans. To assess the physiological significance of these effects, TAG concentrations were monitored following manipulation of the oral exposure pattern and accompanying lipid load. Fifteen healthy adults participated in a randomized, 6-arm, crossover design study. Conditions consisted of ingestion of 30-g loads of safflower oil, provided as capsules to bypass oral stimulation, followed by 15 min of oral stimulation (mastication and expectoration) with full-fat or nonfat cream cheese (conditions 1 and 2); the same oral load ingested intermittently with oral stimulation by both food forms (conditions 3 and 4); and 10-g lipid loads ingested with intermittent oral stimulation by both food forms (conditions 5 and 6). Blood was collected via an indwelling catheter and TAG was measured at minutes -15, 0, 10, 20, 30, 40, 50, 60, 120, 240, and 360 relative to the onset of sensory stimulation. Testing was conducted weekly. Sequential (lipid loading followed by oral stimulation) and intermittent (intermixed lipid loading and oral stimulation) conditions led to comparable TAG responses. Significant first- and second-phase TAG concentration increases were observed with the 30-g loads, but not the 10-g loads. TAG responses to the full-fat and nonfat stimuli were similar. These data support the veracity of the earlier literature based on sequential oral exposure regimens and indicate that TAG responses reflect an interaction between oral fat signaling and gut lipid content. The augmentation of TAG associated specifically with dietary fat exposure, as compared to a nonfat food matched on other sensory properties, may only occur with higher fat loads. PMID- 20352073 TI - Boron-Doped Diamond Microelectrodes Reveal Reduced Serotonin Uptake Rates in Lymphocytes from Adult Rhesus Monkeys Carrying the Short Allele of the 5-HTTLPR. AB - Uptake resolved by high-speed chronoamperometry on a second-by-second basis has revealed important differences in brain serotonin transporter function associated with genetic variability. Here, we use chronoamperometry to investigate variations in serotonin transport in primary lymphocytes associated with the rhesus serotonin transporter gene-linked polymorphism (rh5-HTTLPR), a promoter polymorphism whose orthologs occur only in higher order primates including humans. Serotonin clearance by lymphocytes is Na(+)-dependent and inhibited by the serotonin-selective reuptake inhibitor paroxetine (Paxil(r)), indicative of active uptake by serotonin transporters. Moreover, reductions in serotonin uptake rates are evident in lymphocytes from monkeys with one or two copies of the short 's' allele of the rh5-HTTLPR (s/s7 min, silver islands merge, exhibiting a sharp increase in electrical conductivity. It has been shown that the newly proposed SiF-Glass sample geometry exhibits higher EF values than the commonly used in MEF studies SiF-SiF sample geometry. The SiF Glass geometry demonstrates high sensitivity for surface immunoassays, a growing application of metal-enhanced fluorescence. PMID- 20352079 TI - Genomic and geographic distribution of private SNPs and pathways in human populations. AB - AIMS: Geography-based genetic differentials operating on entire biochemical pathways may reflect different adaptive evolutionary processes that separated populations may have undergone. They may also influence treatment outcome for a variety of drugs - an emerging and important area of study. This research article leverages the International HapMap Consortium data to identify pathway components that differ in genotype frequency for four populations: individuals of Northern European descent from the USA (CEU), individuals from West Africa (YRI), Japan (JPT) and China (CHB). MATERIALS #ENTITYSTARTX00026; METHODS: By identifying loci with fixed or large frequency differences (delta = 1) between paired population samples (CEU vs YRI, CEU vs CHB, CEU vs JPT, YRI vs CHB, YRI vs JPT and CHB vs JPT), and reconstructing the physiological functions of genes at these loci, we report a list of pathways affected by natural selection during human evolution. RESULTS: Of the 3.7 million HapMap SNPs, 463 loci (which mapped to 38 genes) were fixed (delta = 1) in at least one population pair. These private loci included four nonsynonymous coding SNPs: rs4536103 (NEUROG3), rs1385699 (EDA2R), rs11946338 (ARHGAP24) and rs4422842 (CACNA1B). A total of four additional genes demonstrated evidence of recent positive selection: three genes in European subjects (IER5L, NPNT and SESTD1) and a single gene in Asian subjects (EXOC6B). DISCUSSION: Gene ontology and pathway analyses suggest that cellular differentiation, apoptosis and activation of the NF-kappaB transcription factor vary between populations in genomic regions of fixed (private) SNPs identified in this study. Variability in these pathways may provide important clues into the mechanisms of human adaptation to different environments. An improved understanding of their variability may also help to explain race-specific differences in the treatment outcomes observed for a variety of modern drugs. PMID- 20352081 TI - Building National Capacity for Child and Family Disaster Mental Health Research. AB - Disaster mental health is a burgeoning field with numerous opportunities for professional involvement in preparedness, response, and recovery efforts. Research is essential to advance professional understanding of risk and protective factors associated with disaster outcomes; to develop an evidence base for acute, intermediate, and long-term mental health approaches to address child, adult, family, and community disaster-related needs; and to inform policy and guide national and local disaster preparedness, response, and recovery programs. To address the continued need for research in this field, we created the Child & Family Disaster Research Training & Education (DRT) program, which is focused specifically on enhancing national capacity to conduct disaster mental health research related to children, a population particularly vulnerable to disaster trauma. This paper describes the structure and organization of the DRT program, reviews the training curriculum, discusses implementation and evaluation of the program, and reviews obstacles encountered in establishing the program. Finally, key lessons learned are reviewed for the purpose of guiding replication of the DRT model to address other areas of community mental health. PMID- 20352082 TI - Fractionation and evaluation of radical-scavenging peptides from in vitro digests of buckwheat protein. AB - Buckwheat protein (BWP) isolate was subjected to a two-stage in vitro digestion (1 h pepsin followed by 2 h pancreatin at 37 degrees C). The antioxidant potential of the BWP digests was compared by assessing their capacity to scavenge 2,2'-azinobis (3-ethylbenzothiszoline-6-sulphonic acid) (ABTS(+*)) and hydroxyl ((*)OH) radicals. The 2-h pancreatin digest, which demonstrated the strongest activity against both radicals, was subjected to Sephadex G-25 gel filtration. Of the six fractions collected, fractions IV (456 Da) and VI (362 Da) showed the highest ABTS(+*) scavenging activity and were 23-27% superior to mixed BWP digest (P < 0.05). Fraction VI was most effective in neutralizing (*)OH and was 86 and 24% more efficient (P < 0.05) than mixed BWP digest and fraction IV, respectively. LC-MS/MS identified Trp-Pro-Leu, Val-Pro-Trp, and Val-Phe-Pro-Trp (IV), Pro-Trp (V) and tryptophan (VI) to be the prominant peptides/amino acid in these fractions. PMID- 20352077 TI - Stable-isotope dilution LC-MS for quantitative biomarker analysis. AB - The ability to conduct validated analyses of biomarkers is critically important in order to establish the sensitivity and selectivity of the biomarker in identifying a particular disease. The use of stable-isotope dilution (SID) methodology in combination with LC-MS/MS provides the highest possible analytical specificity for quantitative determinations. This methodology is now widely used in the discovery and validation of putative exposure and disease biomarkers. This review will describe the application of SID LC-MS methodology for the analysis of small-molecule and protein biomarkers. It will also discuss potential future directions for the use of this methodology for rigorous biomarker analysis. PMID- 20352084 TI - Viable Three-Dimensional Medical Microwave Tomography: Theory and Numerical Experiments. AB - Three-dimensional microwave tomography represents a potentially very important advance over 2D techniques because it eliminates associated approximations which may lead to more accurate images. However, with the significant increase in problem size, computational efficiency is critical to making 3D microwave imaging viable in practice. In this paper, we present two 3D image reconstruction methods utilizing 3D scalar and vector field modeling strategies, respectively. Finite element (FE) and finite-difference time-domain (FDTD) algorithms are used to model the electromagnetic field interactions in human tissue in 3D. Image reconstruction techniques previously developed for the 2D problem, such as the dual-mesh scheme, iterative block solver, and adjoint Jacobian method are extended directly to 3D reconstructions. Speed improvements achieved by setting an initial field distribution and utilizing an alternating-direction implicit (ADI) FDTD are explored for 3D vector field modeling. The proposed algorithms are tested with simulated data and correctly recovered the position, size and electrical properties of the target. The adjoint formulation and the FDTD method utilizing initial field estimates are found to be significantly more effective in reducing the computation time. Finally, these results also demonstrate that cross plane measurements are critical for reconstructing 3D profiles of the target. PMID- 20352083 TI - Horizontal and vertical movements of host-seeking Ixodes pacificus (Acari: Ixodidae) nymphs in a hardwood forest. AB - The nymph of the western black-legged tick (Ixodes pacificus) is an important bridging vector of the Lyme disease spirochete (Borrelia burgdorferi) to humans in the far-western United States. The previously unknown dispersal capabilities of this life stage were studied in relation to logs, tree trunks, and adjacent leaf-litter areas in a mixed hardwood forest using mark-release-recapture methods. In two spatially and temporally well-spaced trials involving logs, the estimated mean distances that nymphs dispersed ranged from approximately 0.04 to 0.20 m/day on logs vs 0.11 to 0.72 m/day in litter. Prior to recapture in either trial and within the confines of the sampling grids, the greatest estimated dispersal distances by individual nymphs released on logs, and in litter 0.5 m or 1.5 m from logs, were 2.4, 3.0, and 3.0 m, respectively. Nymphs released on logs or litter tended to remain within the same biotopes in which they were freed while host-seeking. In two simultaneous trials involving trunks spaced close-at hand, nymphs released at the trunk/litter interface on all four aspects collectively dispersed a mean of 0.353 m/day on trunks vs 0.175 m/day in litter. In either trial, the greatest distances that recaptured nymphs climbed trunks, or dispersed in litter in an encircling 3-m grid, were 1.55 m and 2.97 m, respectively. Nymphs ascending trunks did not exhibit a preference for any one aspect, and the B. burgdorferi-infection prevalences in nymphs that climbed trunks (3.2-4.0%) did not differ significantly from those that moved horizontally into litter (10.5-17.6%). We conclude that I. pacificus nymphs use an ambush host seeking strategy; that they disperse slowly in all biotopes studied; that they usually continue to host-seek in or on whatever substratum they access initially; and that B. burgdorferi-infected nymphs are as likely to move horizontally as vertically when offered a choice. PMID- 20352085 TI - Cortical thickness and subcortical gray matter reductions in neuropsychiatric systemic lupus erythematosus. AB - Within systemic lupus erythematosus (SLE) patients can be divided into groups with and without central nervous system involvement, the latter being subcategorized as neuropsychiatric systemic lupus erythematosus (NPSLE). While a number of research groups have investigated NPSLE, there remains a lack of consistent application of this diagnostic criteria within neuroimaging studies. Previous neuroimaging research suggests that SLE patients have reduced subcortical and regional gray matter volumes when compared to controls, and that these group differences may be driven by SLE patients with neuropsychiatric symptoms. The current study sought to compare measures of cortical thickness and subcortical structure volume between NPSLE, SLE, and healthy controls. We hypothesized that patients with NPSLE (N = 21) would have thinner cortex and reduced subcortical gray matter volumes when compared to SLE (N = 16) and control subjects (N = 21). All subjects underwent MRI examinations on a 1.5 Tesla Siemens Sonata scanner. Anatomical reconstruction and segmentation were performed using the FreeSurfer image analysis suite. Cortical and subcortical volumes were extracted from FreeSurfer and analyzed for group differences, controlling for age. The NPSLE group exhibited decreased cortical thickness in clusters of the left frontal and parietal lobes as well as in the right parietal and occipital lobes compared to control subjects. Compared to the SLE group, the NPSLE group exhibited comparable thinning in clusters of the frontal and temporal lobes. Controlling for age, we found that between group effects for subcortical gray matter structures were significant for the thalamus (F = 3.06, p = .04), caudate nucleus (F = 3.19, p = .03), and putamen (F = 4.82, p = .005). These results clarify previous imaging work identifying cortical atrophy in a mixed SLE and NPSLE group, and suggest that neuroanatomical abnormalities are specific to SLE patients diagnosed with neuropsychiatric symptoms. Future work should help elucidate the underlying mechanisms underlying the emerging neurobiological profile seen in NPSLE, as well as clarify the apparent lack of overlap between cortical thinning and functional activation results and other findings pointing to increased functional activation during cognitive tasks. PMID- 20352086 TI - The number of cultural traits is correlated with female group size but not with male group size in chimpanzee communities. AB - What determines the number of cultural traits present in chimpanzee (Pan troglodytes) communities is poorly understood. In humans, theoretical models suggest that the frequency of cultural traits can be predicted by population size. In chimpanzees, however, females seem to have a particularly important role as cultural carriers. Female chimpanzees use tools more frequently than males. They also spend more time with their young, skewing the infants' potential for social learning towards their mothers. In Gombe, termite fishing has been shown to be transmitted from mother to offspring. Lastly, it is female chimpanzees that transfer between communities and thus have the possibility of bringing in novel cultural traits from other communities. From these observations we predicted that females are more important cultural carriers than males. Here we show that the reported number of cultural traits in chimpanzee communities correlates with the number of females in chimpanzee communities, but not with the number of males. Hence, our results suggest that females are the carriers of chimpanzee culture. PMID- 20352087 TI - Evaluation of a cluster-randomized controlled trial of a package of community based maternal and newborn interventions in Mirzapur, Bangladesh. AB - BACKGROUND: To evaluate a delivery strategy for newborn interventions in rural Bangladesh. METHODS: A cluster-randomized controlled trial was conducted in Mirzapur, Bangladesh. Twelve unions were randomized to intervention or comparison arm. All women of reproductive age were eligible to participate. In the intervention arm, community health workers identified pregnant women; made two antenatal home visits to promote birth and newborn care preparedness; made four postnatal home visits to negotiate preventive care practices and to assess newborns for illness; and referred sick neonates to a hospital and facilitated compliance. Primary outcome measures were antenatal and immediate newborn care behaviours, knowledge of danger signs, care seeking for neonatal complications, and neonatal mortality. FINDINGS: A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm, respectively. High coverage of antenatal (91% visited twice) and postnatal (69% visited on days 0 or 1) home visitations was achieved. Indicators of care practices and knowledge of maternal and neonatal danger signs improved. Adjusted mortality hazard ratio in the intervention arm, compared to the comparison arm, was 1.02 (95% CI: 0.80-1.30) at baseline and 0.87 (95% CI: 0.68-1.12) at endline. Primary causes of death were birth asphyxia (49%) and prematurity (26%). No adverse events associated with interventions were reported. CONCLUSION: Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation, and improvements in targeted newborn care practices suggests the intervention did not adequately address risk factors for mortality. The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions. Programs must ensure skilled care during childbirth, including management of birth asphyxia and prematurity, and curative postnatal care during the first two days of life, in addition to essential newborn care and infection prevention and management. TRIAL REGISTRATION: Clinicaltrials.gov NCT00198627. PMID- 20352088 TI - Paucity of CD4+ natural killer T (NKT) lymphocytes in sooty mangabeys is associated with lack of NKT cell depletion after SIV infection. AB - Lack of chronic immune activation in the presence of persistent viremia is a key feature that distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection in natural hosts from pathogenic SIV and HIV infection. To elucidate novel mechanisms downmodulating immune activation in natural hosts of SIV infection, we investigated natural killer T (NKT) lymphocytes in sooty mangabeys. NKT lymphocytes are a potent immunoregulatory arm of the innate immune system that recognize glycolipid antigens presented on the nonpolymorphic MHC-class I like CD1d molecules. In a cross-sectional analysis of 50 SIV-negative and 50 naturally SIV-infected sooty mangabeys, ligand alpha-galactosylceramide loaded CD1d tetramers co-staining with Valpha24-positive invariant NKT lymphocytes were detected at frequencies >or=0.002% of circulating T lymphocytes in approximately half of the animals. In contrast to published reports in Asian macaques, sooty mangabey NKT lymphocytes consisted of CD8(+) and CD4/CD8 double-negative T lymphocytes that were CXCR3-positive and CCR5-negative suggesting that they trafficked to sites of inflammation without being susceptible to SIV infection. Consistent with these findings, there was no difference in the frequency or phenotype of NKT lymphocytes between SIV-negative and SIV-infected sooty mangabeys. On stimulation with alpha-galactosylceramide loaded on human CD1d molecules, sooty mangabey NKT lymphocytes underwent degranulation and secreted IFN-gamma, TNF-alpha, IL-2, IL-13, and IL-10, indicating the presence of both effector and immunoregulatory functional capabilities. The unique absence of CD4(+) NKT lymphocytes in sooty mangabeys, combined with their IL-10 cytokine secreting ability and preservation following SIV infection, raises the possibility that NKT lymphocytes might play a role in downmodulating immune activation in SIV-infected sooty mangabeys. PMID- 20352089 TI - The unbearable lightness of health science reporting: a week examining Italian print media. AB - BACKGROUND: Although being an important source of science news information to the public, print news media have often been criticized in their credibility. Health related content of press media articles has been examined by many studies underlining that information about benefits, risks and costs are often incomplete or inadequate and financial conflicts of interest are rarely reported. However, these studies have focused their analysis on very selected science articles. The present research aimed at adopting a wider explorative approach, by analysing all types of health science information appearing on the Italian national press in one-week period. Moreover, we attempted to score the balance of the articles. METHODOLOGY/PRINCIPAL FINDINGS: We collected 146 health science communication articles defined as articles aiming at improving the reader's knowledge on health from a scientific perspective. Articles were evaluated by 3 independent physicians with respect to different divulgation parameters: benefits, costs, risks, sources of information, disclosure of financial conflicts of interest and balance. Balance was evaluated with regard to exaggerated or non correct claims. The selected articles appeared on 41 Italian national daily newspapers and 41 weekly magazines, representing 89% of national circulation copies: 97 articles (66%) covered common medical treatments or basic scientific research and 49 (34%) were about new medical treatments, procedures, tests or products. We found that only 6/49 (12%) articles on new treatments, procedures, tests or products mentioned costs or risks to patients. Moreover, benefits were always maximized and in 16/49 cases (33%) they were presented in relative rather than absolute terms. The majority of stories (133/146, 91%) did not report any financial conflict of interest. Among these, 15 were shown to underreport them (15/146, 9.5%), as we demonstrated that conflicts of interest did actually exist. Unbalanced articles were 27/146 (18%). Specifically, the probability of unbalanced reporting was significantly increased in stories about a new treatment, procedure, test or product (22/49, 45%), compared to stories covering common treatments or basic scientific research (5/97, 5%) (risk ratio, 8.72). CONCLUSIONS/SIGNIFICANCE: Consistent with prior research on health science communication in other countries, we report undisclosed costs and risks, emphasized benefits, unrevealed financial conflicts of interest and exaggerated claims in Italian print media. In addition, we show that the risk for a story about a new medical approach to be unbalanced is almost 9 times higher with respect to stories about any other kind of health science-related topics. These findings raise again the fundamental issue whether popular media is detrimental rather than useful to public health. PMID- 20352090 TI - A new Basal sauropodomorph dinosaur from the Lower Jurassic Navajo sandstone of Southern Utah. AB - BACKGROUND: Basal sauropodomorphs, or 'prosauropods,' are a globally widespread paraphyletic assemblage of terrestrial herbivorous dinosaurs from the Late Triassic and Early Jurassic. In contrast to several other landmasses, the North American record of sauropodomorphs during this time interval remains sparse, limited to Early Jurassic occurrences of a single well-known taxon from eastern North America and several fragmentary specimens from western North America. METHODOLOGY/PRINCIPAL FINDINGS: On the basis of a partial skeleton, we describe here a new basal sauropodomorph dinosaur from the Lower Jurassic Navajo Sandstone of southern Utah, Seitaad ruessi gen. et sp. nov. The partially articulated skeleton of Seitaad was likely buried post-mortem in the base of a collapsed dune foreset. The new taxon is characterized by a plate-like medial process of the scapula, a prominent proximal expansion of the deltopectoral crest of the humerus, a strongly inclined distal articular surface of the radius, and a proximally and laterally hypertrophied proximal metacarpal I. CONCLUSIONS/SIGNIFICANCE: Phylogenetic analysis recovers Seitaad as a derived basal sauropodomorph closely related to plateosaurid or massospondylid 'prosauropods' and its presence in western North America is not unexpected for a member of this highly cosmopolitan clade. This occurrence represents one of the most complete vertebrate body fossil specimens yet recovered from the Navajo Sandstone and one of the few basal sauropodomorph taxa currently known from North America. PMID- 20352091 TI - Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. AB - Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance. PMID- 20352092 TI - Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria. AB - BACKGROUND/AIM: Incomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA beta-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. METHODOLOGY/PRINCIPAL FINDINGS: Large scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 microM; corresponding to low, intermediate and high oxidation rates) and 9 microM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. CONCLUSIONS/SIGNIFICANCE: This proof-of-principle study establishes that large scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle. PMID- 20352093 TI - Captive housing during water vole (Arvicola terrestris) reintroduction: does short-term social stress impact on animal welfare? AB - BACKGROUND: Animals captive bred for reintroduction are often housed under conditions which are not representative of their preferred social structure for at least part of the reintroduction process. Specifically, this is most likely to occur during the final stages of the release programme, whilst being housed during transportation to the release site. The degree of social stress experienced by individuals during this time may negatively impact upon their immunocompetence. METHODOLOGY/PRINCIPAL FINDINGS: We examined two measure of stress--body weight and Leukocyte Coping Capacity (LCC)--to investigate the effects of group size upon captive-bred water voles destined for release within a reintroduction program. Water voles were housed in laboratory cages containing between one and eight individuals. LCC scores were negatively correlated with group size, suggesting that individuals in larger groups experienced a larger degree of immuno-suppression than did individuals housed in smaller groups or individually. During the course of the study mean body weights increased, in contrast to expectations from a previous study. This was attributed to the individuals sampled being sub-adults and thus growing in length and weight during the course of the investigation. CONCLUSIONS/SIGNIFICANCE: The reintroduction process will inevitably cause some stress to the release cohort. However, for water voles we conclude that the stress experienced may be reduced by decreasing group size within captive colony and/or transportation housing practises. These findings are of significance to other species' reintroductions, in highlighting the need to consider life-history strategies when choosing housing systems for animals being maintained in captivity prior to release to the wild. A reduction in stress experienced at the pre-release stage may improve immunocompetence and thus animal welfare and initial survival post-release. PMID- 20352094 TI - Degradation of postsynaptic scaffold GKAP and regulation of dendritic spine morphology by the TRIM3 ubiquitin ligase in rat hippocampal neurons. AB - Changes in neuronal activity modify the structure of dendritic spines and alter the function and protein composition of synapses. Regulated degradation of postsynaptic density (PSD) proteins by the ubiquitin-proteasome system is believed to play an important role in activity-dependent synaptic remodeling. Stimulating neuronal activity in vitro and in vivo induces the ubiquitination and degradation of GKAP/SAPAP and Shank, major scaffold proteins of the PSD. However, the specific ubiquitin ligases that regulate postsynaptic protein composition have not been identified. Here we identify the RING finger-containing protein TRIM3 as a specific E3 ubiquitin ligase for the PSD scaffold GKAP/SAPAP1. Present in PSD fractions from rat brain, TRIM3 stimulates ubiquitination and proteasome dependent degradation of GKAP, and induces the loss of GKAP and associated scaffold Shank1 from postsynaptic sites. Suppression of endogenous TRIM3 by RNA interference (RNAi) results in increased accumulation of GKAP and Shank1 at synapses, as well as enlargement of dendritic spine heads. RNAi of TRIM3 also prevented the loss of GKAP induced by synaptic activity. Thus, TRIM3 is a novel E3 ligase that mediates activity-dependent turnover of PSD scaffold proteins and is a negative regulator of dendritic spine morphology. PMID- 20352095 TI - Long-term depression in the hippocampal CA1 area of aged rats, revisited: contribution of temporal constraints related to slice preparation. AB - BACKGROUND: The effects of low-frequency conditioning stimulation (LFS, 900 pulses at 1 Hz) of glutamatergic afferents in CA1 hippocampal area using slices from two different strains of adult (3-5 month-old) and aged (23-27 month-old) rats were reinvestigated regarding the discrepancies in the literature concerning the expression of long-term depression (LTD) in the aging brain. METHODOLOGY/PRINCIPAL FINDINGS: N-methyl-D-aspartate receptor (NMDA-R) dependent LTD was examined in both adult (n = 21) and aged (n = 22) Sprague-Dawley rats. While equivalent amounts of LTD could be obtained in both ages, there was significant variability depending upon the time between the slices were made and when they were tested. LTD was not apparent if slices were tested within 3 hours of dissection. The amount of LTD increased over the next three hours but more in adult than in aged rats. This age-related impairment was abolished by exogenous d serine, thus reflecting the reduced activation of the NMDA-R glycine-binding site by the endogenous agonist in aged rats. Then, the amount of LTD reached asymptote at 5-7 hours following dissection. Similar temporal profiles of LTD expression were seen in young and aged Wistar rats. CONCLUSIONS/SIGNIFICANCE: Taken together, these results sound a cautionary note regarding the existence of an experimental "window of opportunity" for studying the effects of aging on LTD expression in hippocampal slice preparation. PMID- 20352096 TI - Fungal-mediated multitrophic interactions--do grass endophytes in diet protect voles from predators? AB - Plant-associated micro-organisms such as mycotoxin-producing endophytes commonly have direct negative effects on herbivores. These effects may be carried over to natural enemies of the herbivores, but this has been rarely explored. We examined how feeding on Neotyphodium endophyte infected (E+) and endophyte free (E-) meadow ryegrass (Scherodonus pratensis) affects body mass, population size and mobility of sibling voles (Microtus levis), and whether the diet mediates the vulnerability of voles to least weasel (Mustela nivalis nivalis) predation. Because least weasels are known to be olfactory hunters, we also examined whether they are able to distinguish olfactory cues of voles fed on E+ and E- diets. Neither body mass of voles nor population size differed between diets. However, contrary to our prediction, least weasels preyed more often on voles fed with E- grass than on voles fed with E+ grass. The mobility of voles fed on E+ grass was reduced compared to voles fed on E- grass, but this effect was unrelated to risk of predation. Least weasels appeared unable to distinguish between excrement odours of voles between the two treatments. Our results suggest that consumption of endophytic grass is not directly deleterious to sibling voles. What's more, consumption of endophytes appears to be advantageous to voles by reducing risk of mammalian predation. Our study is thus the first to demonstrate an effect of plant-associated microbial symbionts on herbivore-predator interactions in vertebrate communities. PMID- 20352097 TI - Chromosomal manipulation by site-specific recombinases and fluorescent protein based vectors. AB - Feasibility of chromosomal manipulation in mammalian cells was first reported 15 years ago. Although this technique is useful for precise understanding of gene regulation in the chromosomal context, a limited number of laboratories have used it in actual practice because of associated technical difficulties. To overcome the practical hurdles, we developed a Cre-mediated chromosomal recombination system using fluorescent proteins and various site-specific recombinases. These techniques enabled quick construction of targeting vectors, easy identification of chromosome-rearranged cells, and rearrangement leaving minimum artificial elements at junctions. Applying this system to a human cell line, we successfully recapitulated two types of pathogenic chromosomal translocations in human diseases: MYC/IgH and BCR/ABL1. By inducing recombination between two loxP sites targeted into the same chromosome, we could mark cells harboring deletion or duplication of the inter-loxP segments with different colors of fluorescence. In addition, we demonstrated that the intrachromosomal recombination frequency is inversely proportional to the distance between two recombination sites, implicating a future application of this frequency as a proximity sensor. Our method of chromosomal manipulation can be employed for particular cell types in which gene targeting is possible (e.g. embryonic stem cells). Experimental use of this system would open up new horizons in genome biology, including the establishment of cellular and animal models of diseases caused by translocations and copy-number variations. PMID- 20352098 TI - Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. AB - BACKGROUND: The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB(R)-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated. METHODS: LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis. RESULTS: Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm(3) (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%-100%). 25% of smear negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm(3) were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species. CONCLUSIONS: These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm(3), who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection. PMID- 20352099 TI - Direct reprogramming of rat neural precursor cells and fibroblasts into pluripotent stem cells. AB - BACKGROUND: Given the usefulness of rats as an experimental system, an efficient method for generating rat induced pluripotent stem (iPS) cells would provide researchers with a powerful tool for studying human physiology and disease. Here, we report direct reprogramming of rat neural precursor (NP) cells and rat embryonic fibroblasts (REF) into iPS cells by retroviral transduction using either three (Oct3/4, Sox2, and Klf4), four (Oct3/4, Sox2, Klf4, and c-Myc), or five (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) genes. METHODOLOGY AND PRINCIPAL FINDINGS: iPS cells were generated from both NP and REF using only three (Oct3/4, Sox2, and Klf4) genes without c-Myc. Two factors were found to be critical for efficient derivation and maintenance of rat iPS cells: the use of rat instead of mouse feeders, and the use of small molecules specifically inhibiting mitogen activated protein kinase and glycogen synthase kinase 3 pathways. In contrast, introduction of embryonic stem cell (ESC) extracts induced partial reprogramming, but failed to generate iPS cells. However, when combined with retroviral transduction, this method generated iPS cells with significantly higher efficiency. Morphology, gene expression, and epigenetic status confirmed that these rat iPS cells exhibited ESC-like properties, including the ability to differentiate into all three germ layers both in vitro and in teratomas. In particular, we found that these rat iPS cells could differentiate to midbrain like dopamine neurons with a high efficiency. CONCLUSIONS/SIGNIFICANCE: Given the usefulness of rats as an experimental system, our optimized method would be useful for generating rat iPS cells from diverse tissues and provide researchers with a powerful tool for studying human physiology and disease. PMID- 20352100 TI - Discovery of Phytophthora infestans genes expressed in planta through mining of cDNA libraries. AB - BACKGROUND: Phytophthora infestans (Mont.) de Bary causes late blight of potato and tomato, and has a broad host range within the Solanaceae family. Most studies of the Phytophthora--Solanum pathosystem have focused on gene expression in the host and have not analyzed pathogen gene expression in planta. METHODOLOGY/PRINCIPAL FINDINGS: We describe in detail an in silico approach to mine ESTs from inoculated host plants deposited in a database in order to identify particular pathogen sequences associated with disease. We identified candidate effector genes through mining of 22,795 ESTs corresponding to P. infestans cDNA libraries in compatible and incompatible interactions with hosts from the Solanaceae family. CONCLUSIONS/SIGNIFICANCE: We annotated genes of P. infestans expressed in planta associated with late blight using different approaches and assigned putative functions to 373 out of the 501 sequences found in the P. infestans genome draft, including putative secreted proteins, domains associated with pathogenicity and poorly characterized proteins ideal for further experimental studies. Our study provides a methodology for analyzing cDNA libraries and provides an understanding of the plant--oomycete pathosystems that is independent of the host, condition, or type of sample by identifying genes of the pathogen expressed in planta. PMID- 20352101 TI - Parasite polymorphism and severe malaria in Dakar (Senegal): a West African urban area. AB - BACKGROUND: Transmission of malaria in West African urban areas is low and healthcare facilities are well organized. However, malaria mortality remains high. We conducted a survey in Dakar with the general objective to establish who died from severe malaria (SM) in urban areas (particularly looking at the age groups) and to compare parasite isolates associated with mild or severe malaria. METHODOLOGY/PRINCIPAL FINDINGS: The current study included mild- (MM) and severe malaria (SM) cases, treated in dispensaries (n = 2977) and hospitals (n = 104), We analysed Pfdhfr/Pfcrt-exon2 and nine microsatellite loci in 102 matched cases of SM and MM. Half of the malaria cases recorded at the dispensaries and 87% of SM cases referred to hospitals, occurred in adults, although adults only accounted for 26% of all dispensary consultations. This suggests that, in urban settings, whatever the reason for this adult over-representation, health-workers are forced to take care of increasing numbers of malaria cases among adults. Inappropriate self treatment and mutations in genes associated with drug resistance were found associated with SM in adults. SM was also associated with a specific pool of isolates highly polymorphic and different from those associated with MM. CONCLUSION: In this urban setting, adults currently represent one of the major groups of patients attending dispensaries for malaria treatment. For these patients, despite the low level of transmission, SM was associated with a specific and highly polymorphic pool of parasites which may have been selected by inappropriate treatment. PMID- 20352102 TI - Nucleocytoplasmic distribution and dynamics of the autophagosome marker EGFP-LC3. AB - The process of autophagy involves the formation of autophagosomes, double membrane structures that encapsulate cytosol. Microtubule-associated protein light chain 3 (LC3) was the first protein shown to specifically label autophagosomal membranes in mammalian cells, and subsequently EGFP-LC3 has become one of the most widely utilized reporters of autophagy. Although LC3 is currently thought to function primarily in the cytosol, the site of autophagosome formation, EGFP-LC3 often appears to be enriched in the nucleoplasm relative to the cytoplasm in published fluorescence images. However, the nuclear pool of EGFP LC3 has not been specifically studied in previous reports, and mechanisms by which LC3 shuttles between the cytoplasm and nucleoplasm are currently unknown. In this study, we therefore investigated the regulation of the nucleo-cytoplasmic distribution of EGFP-LC3 in living cells. By quantitative fluorescence microscopy analysis, we demonstrate that soluble EGFP-LC3 is indeed enriched in the nucleus relative to the cytoplasm in two commonly studied cell lines, COS-7 and HeLa. Although LC3 contains a putative nuclear export signal (NES), inhibition of active nuclear export or mutation of the NES had no effect on the nucleo cytoplasmic distribution of EGFP-LC3. Furthermore, FRAP analysis indicates that EGFP-LC3 undergoes limited passive nucleo-cytoplasmic transport under steady state conditions, and that the diffusional mobility of EGFP-LC3 was substantially slower in the nucleus and cytoplasm than predicted for a freely diffusing monomer. Induction of autophagy led to a visible decrease in levels of soluble EGFP-LC3 relative to autophagosome-bound protein, but had only modest effects on the nucleo-cytoplasmic ratio or diffusional mobility of the remaining soluble pools of EGFP-LC3. We conclude that the enrichment of soluble EGFP-LC3 in the nucleus is maintained independently of active nuclear export or induction of autophagy. Instead, incorporation of soluble EGFP-LC3 into large macromolecular complexes within both the cytoplasm and nucleus may prevent its rapid equilibrium between the two compartments. PMID- 20352103 TI - A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells. AB - BACKGROUND: Cell survival mediated by integrin engagement has been implicated in cell adhesion-mediated drug resistance. We have recently demonstrated that the activation of glycogen synthase kinase 3 beta (GSK3beta) is a new pathway supporting the chemoresistance of leukemic cells adhered to fibronectin. METHODOLOGY AND PRINCIPAL FINDINGS: We show here that in conditions of serum starvation, the fibronectin receptor alpha(5)beta(1) integrin, but not alpha(4)beta(1), induced activation of GSK3beta through Ser-9 dephosphorylation in adherent U937 cells. The GSK3beta-dependent survival pathway occurred in adherent leukemic cells from patients but not in the HL-60 and KG1 cell lines. In adhesion, activated GSK3beta was found in the cytosol/plasma membrane compartment and was co-immunoprecipitated with alpha(5) integrin, the phosphatase PP2A and the scaffolding protein RACK1. PP2A and its regulatory subunit B' regulated the Ser-9 phosphorylation of GSK3beta. In adherent leukemic cells, alpha(5)beta(1) integrin but not alpha(4)beta(1) upregulated the resistance to TNFalpha-induced apoptosis. Both extrinsic and intrinsic apoptotic pathways were under the control of alpha(5)beta(1) and GSK3beta. CONCLUSIONS AND SIGNIFICANCE: Our data show that, upon serum starvation, alpha(5)beta(1) integrin engagement could regulate specific pro-survival functions through the activation of GSK3beta. PMID- 20352104 TI - Adaptation of group A Streptococcus to human amniotic fluid. AB - BACKGROUND: For more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated. However, within the last three decades there has been an increase in severe intra- and post-partum infections attributed to GAS. METHODOLOGY: We hypothesized that GAS alters its transcriptome to survive in human amniotic fluid (AF) and cause disease. To identify genes that were up or down regulated in response to growth in AF, GAS was grown in human AF or standard laboratory media (THY) and samples for expression microarray analysis were collected during mid-logarithmic, late-logarithmic, and stationary growth phases. Microarray analysis was performed using a custom Affymetrix chip and normalized hybridization values derived from three biological replicates were collected at each growth point. Ratios of AF/THY above a 2-fold change and P value <0.05 were considered significant. PRINCIPAL FINDINGS: The majority of changes in the GAS transcriptome involved down regulation of multiple adhesins and virulence factors and activation of the stress response. We observed significant changes in genes involved in the arginine deiminase pathway and in the nucleotide de novo synthesis pathway. CONCLUSIONS/SIGNIFICANCE: Our work provides new insight into how pathogenic bacteria respond to their environment to establish infection and cause disease. PMID- 20352105 TI - In the absence of frazzled over-expression of Abelson tyrosine kinase disrupts commissure formation and causes axons to leave the embryonic CNS. AB - BACKGROUND: In the Drosophila embryonic nerve cord, the formation of commissures require both the chemoattractive Netrin receptor Frazzled (Fra) and the Abelson (Abl) cytoplasmic tyrosine kinase. Abl binds to the cytoplasmic domain of Fra and loss-of-function mutations in abl enhance fra-dependent commissural defects. To further test Abl's role in attractive signaling, we over-expressed Abl in Fra mutants anticipating rescue of commissures. METHODOLOGY/PRINCIPAL FINDINGS: The Gal4-UAS system was used to pan-neurally over-express Abl in homozygous fra embryos. Surprisingly, this led to a significant decrease in both posterior and anterior commissure formation and induced some commissural and longitudinal axons to project beyond the CNS/PNS border. Re-expressing wild-type Fra, or Fra mutants with a P-motif deleted, revert both commissural and exiting phenotypes, indicating that Fra is required but not a specific P-motif. This is supported by S2 cell experiments demonstrating that Abl binds to Fra independent of any specific P-motif and that Fra continues to be phosphorylated when individual P motifs are removed. Decreasing midline repulsion by reducing Robo signaling had no effect on the Abl phenotype and the phenotypes still occur in a Netrin mutant. Pan-neural over-expression of activated Rac or Cdc42 in a fra mutant also induced a significant loss in commissures, but axons did not exit the CNS. CONCLUSION/SIGNIFICANCE: Taken together, these data suggest that Fra activity is required to correctly regulate Abl-dependent cytoskeletal dynamics underlying commissure formation. In the absence of Fra, increased Abl activity appears to be incorrectly utilized downstream of other guidance receptors resulting in a loss of commissures and the abnormal projections of some axons beyond the CNS/PNS border. PMID- 20352107 TI - HIV-1 fusion inhibitor peptides enfuvirtide and T-1249 interact with erythrocyte and lymphocyte membranes. AB - Enfuvirtide and T-1249 are two HIV-1 fusion inhibitor peptides that bind to gp41 and prevent its fusogenic conformation, inhibiting viral entry into host cells. Previous studies established the relative preferences of these peptides for membrane model systems of defined lipid compositions. We aimed to understand the interaction of these peptides with the membranes of erythrocytes and peripheral blood mononuclear cells. The peptide behavior toward cell membranes was followed by di-8-ANEPPS fluorescence, a lipophilic probe sensitive to the changes in membrane dipole potential. We observed a fusion inhibitor concentration-dependent decrease on the membrane dipole potential. Quantitative analysis showed that T 1249 has an approximately eight-fold higher affinity towards cells, when compared with enfuvirtide. We also compared the binding towards di-8-ANEPPS labeled lipid vesicles that model cell membranes and obtained concordant results. We demonstrated the distinct enfuvirtide and T-1249 membranotropism for circulating blood cells, which can be translated to a feasible in vivo scenario. The enhanced interaction of T-1249 with cell membranes correlates with its higher efficacy, as it can increase and accelerate the drug binding to gp41 in its pre-fusion state. PMID- 20352106 TI - 4E10-resistant HIV-1 isolated from four subjects with rare membrane-proximal external region polymorphisms. AB - Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10 resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. For all three subjects with W680 polymorphisms, we observed additional residues in the MPER that co varied with position 680 and preserved charged distributions across this region. Our data provide important caveats for vaccine development targeting the MPER. Naturally occurring Env variants described in our study also represent unique tools for probing the structure-function of HIV-1 envelope. PMID- 20352109 TI - Association of the CTLA4 gene with Graves' disease in the Chinese Han population. AB - To determine whether genetic heterogeneity exists in patients with Graves' disease (GD), the cytotoxic T-lymphocyte associated 4 (CTLA-4) gene, which is implicated a susceptibility gene for GD by considerable genetic and immunological evidence, was used for association analysis in a Chinese Han cohort recruited from various geographic regions. Our association study for the SNPs in the CTLA4 gene in 2640 GD patients and 2204 control subjects confirmed that CTLA4 is the susceptibility gene for GD in the Chinese Han population. Moreover, the logistic regression analysis in the combined Chinese Han cohort revealed that SNP rs231779 (allele frequencies p = 2.81x10(-9), OR = 1.35, and genotype distributions p = 2.75x10(-9), OR = 1.42) is likely the susceptibility variant for GD. Interestingly, the logistic regression analysis revealed that SNP rs35219727 may be the susceptibility variant to GD in the Shandong population; however, SNP, rs231779 in the CTLA4 gene probably independently confers GD susceptibility in the Xuzhou and southern China populations. These data suggest that the susceptibility variants of the CTLA4 gene varied between the different geographic populations with GD. PMID- 20352108 TI - Induction of autophagy by cystatin C: a mechanism that protects murine primary cortical neurons and neuronal cell lines. AB - Cystatin C (CysC) expression in the brain is elevated in human patients with epilepsy, in animal models of neurodegenerative conditions, and in response to injury, but whether up-regulated CysC expression is a manifestation of neurodegeneration or a cellular repair response is not understood. This study demonstrates that human CysC is neuroprotective in cultures exposed to cytotoxic challenges, including nutritional-deprivation, colchicine, staurosporine, and oxidative stress. While CysC is a cysteine protease inhibitor, cathepsin B inhibition was not required for the neuroprotective action of CysC. Cells responded to CysC by inducing fully functional autophagy via the mTOR pathway, leading to enhanced proteolytic clearance of autophagy substrates by lysosomes. Neuroprotective effects of CysC were prevented by inhibiting autophagy with beclin 1 siRNA or 3-methyladenine. Our findings show that CysC plays a protective role under conditions of neuronal challenge by inducing autophagy via mTOR inhibition and are consistent with CysC being neuroprotective in neurodegenerative diseases. Thus, modulation of CysC expression has therapeutic implications for stroke, Alzheimer's disease, and other neurodegenerative disorders. PMID- 20352110 TI - Versatile virus-like particle carrier for epitope based vaccines. AB - BACKGROUND: Recombinant proteins and in particular single domains or peptides are often poorly immunogenic unless conjugated to a carrier protein. Virus-like particles are a very efficient means to confer high immunogenicity to antigens. We report here the development of virus-like-particles (VLPs) derived from the RNA bacteriophage AP205 for epitope-based vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Peptides of angiotensin II, S.typhi outer membrane protein (D2), CXCR4 receptor, HIV1 Nef, gonadotropin releasing hormone (GnRH), Influenza A M2-protein were fused to either N- or C-terminus of AP205 coat protein. The A205-peptide fusions assembled into VLPs, and peptides displayed on the VLP were highly immunogenic in mice. GnRH fused to the C-terminus of AP205 induced a strong antibody response that inhibited GnRH function in vivo. Exposure of the M2 protein peptide at the N-terminus of AP205 resulted in a strong M2-specific antibody response upon immunization, protecting 100% of mice from a lethal influenza infection. CONCLUSIONS/SIGNIFICANCE: AP205 VLPs are therefore a very efficient and new vaccine system, suitable for complex and long epitopes, of up to at least 55 amino acid residues in length. AP205 VLPs confer a high immunogenicity to displayed epitopes, as shown by inhibition of endogenous GnRH and protective immunity against influenza infection. PMID- 20352111 TI - Sensitive detection of gene expression in mycobacteria under replicating and non replicating conditions using optimized far-red reporters. AB - Fluorescent reporter proteins have proven useful for imaging techniques in many organisms. We constructed optimized expression systems for several fluorescent proteins from the far-red region of the spectrum and analyzed their utility in several mycobacterial species. Plasmids expressing variants of the Discosoma Red fluorescent protein (DsRed) from the Mycobacterium bovis hsp60 promoter were unstable; in contrast expression from the Mycobacterium smegmatis rpsA promoter was stable. In Mycobacterium tuberculosis expression of several of the far-red reporters was readily visualised by eye and three reporters (mCherry, tdTomato, and Turbo-635) fluoresced at a high intensity. Strains expressing mCherry showed no fitness defects in vitro or in macrophages. Treatment of cells with antibiotics demonstrated that mCherry could also be used as a reporter for cell death, since fluorescence decreased in the presence of a bactericidal compound, but remained stable in the presence of a bacteriostatic compound. mCherry was functional under hypoxic conditions; using mCherry we demonstrated that the P(mtbB) is expressed early in hypoxia and progressively down-regulated. mCherry and other far-red fluorescent proteins will have multiple uses in investigating the biology of mycobacteria, particularly under non-replicating, or low cell density conditions, as well as providing a novel means of detecting cell death rapidly. PMID- 20352113 TI - Sex-related differences in reproductive allocation, growth, defense and herbivory in three dioecious neotropical palms. AB - BACKGROUND: Frequently, in dioecious plants, female plants allocate more resources to reproduction than male plants. Therefore it is expected that asymmetrical allocation to reproduction may lead to a reproduction-growth tradeoff, whereby female plants grow less than male plants, but invest more in defenses and thus experience lower herbivory than male plants. METHODOLOGY/PRINCIPAL FINDINGS: We tested these expectations by comparing resource allocation to reproduction, growth and defense and its consequences on herbivory in three sympatric dioecious Chamaedorea palms (C. alternans, C. pinnatifrons and C. ernesti-augusti) using a pair-wise design (replicated male/female neighboring plants) in a Mexican tropical rain forest. Our findings support the predictions. Biomass allocation to reproduction in C. pinnatifrons was 3-times higher in female than male plants, consistent with what is known in C. alternans and C. ernesti-augusti. Growth (height and leaf production rate and biomass production) was higher in male plants of all three species. Female plants of the three species had traits that suggest greater investment in defense, as they had 4-16% tougher leaves, and 8-18% higher total phenolic compounds concentration. Accordingly, female plants sustained 53-78% lower standing herbivory and 49-87% lower herbivory rates than male plants. CONCLUSIONS/SIGNIFICANCE: Our results suggests that resource allocation to reproduction in the studied palms is more costly to female plants and this leads to predictable intersexual differences in growth, defense and herbivory. We conclude that resource allocation to reproduction in plants can have important consequences that influence their interaction with herbivores. Since herbivory is recognized as an important selective force in plants, these results are of significance to our understanding of plant defense evolution. PMID- 20352112 TI - Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene based vaccination against H5N1 influenza in mouse and ferret. AB - Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. PMID- 20352114 TI - Within and between whorls: comparative transcriptional profiling of Aquilegia and Arabidopsis. AB - BACKGROUND: The genus Aquilegia is an emerging model system in plant evolutionary biology predominantly because of its wide variation in floral traits and associated floral ecology. The anatomy of the Aquilegia flower is also very distinct. There are two whorls of petaloid organs, the outer whorl of sepals and the second whorl of petals that form nectar spurs, as well as a recently evolved fifth whorl of staminodia inserted between stamens and carpels. METHODOLOGY/PRINCIPAL FINDINGS: We designed an oligonucleotide microarray based on EST sequences from a mixed tissue, normalized cDNA library of an A. formosa x A. pubescens F2 population representing 17,246 unigenes. We then used this array to analyze floral gene expression in late pre-anthesis stage floral organs from a natural A. formosa population. In particular, we tested for gene expression patterns specific to each floral whorl and to combinations of whorls that correspond to traditional and modified ABC model groupings. Similar analyses were performed on gene expression data of Arabidopsis thaliana whorls previously obtained using the Ath1 gene chips (data available through The Arabidopsis Information Resource). CONCLUSIONS/SIGNIFICANCE: Our comparative gene expression analyses suggest that 1) petaloid sepals and petals of A. formosa share gene expression patterns more than either have organ-specific patterns, 2) petals of A. formosa and A. thaliana may be independently derived, 3) staminodia express B and C genes similar to stamens but the staminodium genetic program has also converged on aspects of the carpel program and 4) staminodia have unique up regulation of regulatory genes and genes that have been implicated with defense against microbial infection and herbivory. Our study also highlights the value of comparative gene expression profiling and the Aquilegia microarray in particular for the study of floral evolution and ecology. PMID- 20352115 TI - Associations between total cerebral blood flow and age related changes of the brain. AB - BACKGROUND AND PURPOSE: Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow. MATERIALS AND METHODS: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min. RESULTS: We found a significant correlation between tCBF in mL/min and both age (r = -.124; p = p0.05). However, histological activity, the number of reflux episodes and the number of reflux episodes lasting longer than 5 min were significantly decreased only in group D (P<0.05). The total per cent of bilirubin absorption (value of 0.14 units or greater) time was decreased in groups B, C and D, and most significantly in group D (P<0.05). CONCLUSION: Rabeprazole combined with hydrotalcite is an effective therapeutic option in the treatment of patients with bile reflux gastritis after cholecystectomy. PMID- 20352151 TI - Stem cells for myocardial repair. AB - There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myocardial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy. PMID- 20352152 TI - Association of common genetic variations and idiopathic venous thromboembolism. Results from EDITh, a hospital-based case-control study. AB - Venous thromboembolism (VTE) is a multifactorial disease, caused by interacting environmental and genetic risk factors. Gene-centric genotyping strategy is one of the approaches to explore unexplained associations between risk factors and VTE. It was the objective of this study to evaluate, using a gene-centric genotyping strategy, polymorphisms in genes involved in the following pathways: coagulation cascade process, renin-angiotensin or adrenergic systems, lipid metabolism, platelet aggregation. Allele frequency was compared between 677 cases with idiopathic VTE and their matched controls. After Bonferroni adjustment, four single nucleotide polymorphisms (SNPs) were significantly associated with VTE: Factor XI rs925451 polymorphism, factor XI rs2289252 polymorphism, factor II rs1799963 (G20210A) polymorphism and factor V Leiden rs6025. An additive mode of inheritance fitted best both factor XI polymorphisms. In this hospital-based case control study, two polymorphisms located on the factor XI gene were significantly associated with VTE. Other newly investigated polymorphisms with potentially false negatives may warrant further analyses. PMID- 20352153 TI - Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart. AB - Unexplained bleeding episodes are associated with ventricular assist devices (VAD) and can occur in part due to acquired von Willebrand syndrome (AVWS). AVWS is characterised by loss of high molecular weight (HMW) multimers of von Willebrand factor (VWF) and decreased ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. Loss of multimers can occur as VWF is subjected to increased shear stress, which occurs in presence of VADs. We studied 12 patients who required mechanical support of their native heart for terminal cardiac insufficiency. Nine patients underwent placement of a VAD, while three underwent placement of a total artificial heart (TAH), which is connected directly to heart and large cardiac vessels without cannulas. Within one day of VAD implantation, four of five patients evaluated demonstrated loss of HMW multimers and impaired VWF function. AVWS was present within two weeks of implantation in eight of nine patients, and in all seven tested patients after >/=3 months. Patients with different VAD types developed varying severities of AVWS. After VAD explantation, HMW multimers were detectable and VWF function normalised in all patients. AVWS was not observed in the TAH patients studied. Our findings demonstrate that patients with an implanted VAD experience a rapid onset of AVWS that is quickly and completely reversed after device explantation. In addition, TAH patients do not develop AVWS. These results suggest that shear stress associated with exposure of blood to VAD cannulas and tubes may contribute to the development of AVWS. PMID- 20352154 TI - The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response. AB - Clopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P glycoprotein (Pgp), which mediates clopidogrel's intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 muM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 muM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on clopidogrel platelet reactivity was significantly higher in both users of Pgp inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodipine was associated with clopidogrel poor response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs. PMID- 20352155 TI - A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease. AB - Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA 100 induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4-12%), during aspirin treatment (3-46%) and for day-to-day variability (3-37%) differed markedly between tests and were lowest for VerifyNow. The prevalence of aspirin low-responsiveness also differed between tests (0-9%) and the agreement was low: kappa 11G/l: 9.73, 95% confidence interval 1.98-47.9, p=0.005). The risk associated with leukocytosis was independent from C-reactive protein level. Thrombocyte count and type of treatment (allogeneic vs. autologous transplantation vs. chemotherapy) had no significant influence on thrombosis development. In three cohorts of patients undergoing intensive cytoreductive treatment for haematological malignancy, leukocyte count was strongly associated with development of thrombotic complications. PMID- 20352162 TI - 4G/5G polymorphism and haplotypes of SERPINE1 in atherosclerotic diseases of coronary arteries. AB - We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p 1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99-1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00-1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis. PMID- 20352163 TI - Heterozygous antithrombin deficiency improves in vivo haemostasis in factor VIII deficient mice. AB - Decreased levels of factor VIII (FVIII) limit the amount of thrombin generated at the site of injury, but not the rate that thrombin is neutralised by antithrombin (AT). We hypothesised that FVIII-deficient mice with heterozygous AT deficiency will demonstrate increased thrombin generation and therefore less in vivo bleeding compared to FVIII-deficient mice with normal AT levels. Therefore, we performed tail bleeding experiments in wild-type (WT), heterozygous AT deficient (AT(+/-)) mice, FVIII-deficient (FVIII(-/-)) mice, and FVIII-deficient mice with heterozygous AT deficiency (FVIII(-/-)/AT(+/-)). Amount of bleeding was assessed by measuring absorbance of haemoglobin released from lysed red blood cells collected after tail transection. In addition, we measured thrombin generation, activated partial thromboplastin time (aPTT), and AT activity in plasma from the different mice groups. Tail bleeding was significantly reduced in FVIII(-/ )/AT(+/-) mice compared to FVIII(-/-) mice. On the other hand, there was no difference in tail bleeding between AT(+/-) and wild-type mice. Thrombin generation was dependent on the mice genotype, and increased in the following order: FVIII(-/-) < FVIII(-/-)/AT(+/-) < WT < AT(+/-). The aPTT was not influenced by reduced AT activity (i.e. AT(+/-) genotype), but was significantly prolonged in FVIII(-/-) and FVIII(-/-)/AT(+/-) mice. Using FVIII-deficient mice as an in vivo murine model of reduced thrombin generation, we demonstrated that moderately reduced AT levels increase thrombin generation and decrease bleeding after traumatic tail vessel injury. In agreement with congenital thrombotic conditions, our data elucidate that bleeding phenotypes can be modulated by the balance between procoagulant and anticoagulant proteins. PMID- 20352164 TI - Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides. AB - We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin. PMID- 20352165 TI - Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo. AB - The endothelial protein C receptor (EPCR) plays an anticoagulant role by improving protein C activation. Although low levels of activated protein C (APC) constitute a thrombosis risk factor, the relationship between modulating EPCR function and thrombosis has not been addressed so far. Monoclonal antibodies (mAb) against murine EPCR were raised, and their ability to block protein C/APC binding was tested. The ferric chloride carotid artery injury model in mice was chosen to test the effect of anti-EPCR mAb on thrombus formation. The time to total occlusion of the vessel was analysed in three groups, given an isotype control mAb (IC), a blocking (RCR-16) or a non-blocking (RCR-20) anti-EPCR mAb. RCR-16 prevented the interaction between protein C/APC and EPCR as demonstrated by surface plasmon resonance and flow cytometry, and inhibited the activation of protein C on the endothelium. IC and RCR-20 were unable to induce such effects. In vivo , RCR-16 shortened the time to total vessel occlusion with respect to IC [13.4 +/- 1.0 (mean +/- SD) and 17.8 +/- 3.2 minutes, respectively, p<0.001]. Occlusive thrombi lasting for more than one hour were observed in all RCR-16 treated animals, but only in 43% of IC-treated ones. Results with RCR-20 were indistinguishable from those observed with IC. For the first time, a direct relationship between blocking EPCR and thrombosis is demonstrated. Blocking anti EPCR autoantibodies can predispose to thrombosis episodes and may constitute a new therapeutic target. PMID- 20352166 TI - Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. AB - Dabigatran etexilate is an oral, reversible direct thrombin inhibitor that is approved in the EU and several other countries for the prevention of venous thromboembolism after elective hip and knee replacement, and is in advanced clinical development for other thromboembolic disorders. Dabigatran has a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for routine coagulation monitoring. In certain clinical situations such as serious bleeding into critical organs (e.g. intracerebral bleeding), potential overdose and emergency surgery, clinicians will need to make an assessment of the anticoagulant status of a patient receiving dabigatran before deciding on future management strategies. If available, thrombin clotting time (TT), ecarin clotting time (ECT) and TT determined by Hemoclot thrombin inhibitor assay are sensitive tests to evaluate the anticoagulant effects of dabigatran. Prothrombin time (INR) is less sensitive than other assays and cannot be recommended. The activated partial thromboplastin time (aPTT) can provide a useful qualitative assessment of anticoagulant activity but is less sensitive at supratherapeutic dabigatran levels. There are limited data for activated clotting time (ACT). Overall, the aPTT and TT are the most accessible qualitative methods for determining the presence or absence of anticoagulant effect. Although there is no specific antidote to antagonise the anticoagulant effect of dabigatran, due to its short duration of effect drug discontinuation is usually sufficient to reverse any excessive anticoagulant activity. In case of potential overdose, the feasibility of early administration of activated charcoal and subsequent charcoal filtration are undergoing preclinical evaluation. Dabigatran can also be dialysed in patients with renal impairment. In instances of life-threatening bleeding, where conventional measures have failed or are unavailable, other non-specific prohaemostatic agents such as recombinant activated factor VII and prothrombin complex concentrates can be considered. PMID- 20352167 TI - Comorbidities, alone and in combination with D-dimer, as risk factors for recurrence after a first episode of unprovoked venous thromboembolism in the extended follow-up of the PROLONG study. AB - The PROLONG randomised clinical trial showed that an abnormal D-dimer at one month after vitamin K antagonist (VKA) suspension for a first episode of unprovoked venous thromboembolism (VTE) is associated with a higher risk of recurrence. However, other patient characteristics, such as comorbidities, in combination with D-dimer could also influence the recurrence risk. It was the objective of this study to assess the predictive value of comorbidities and D dimer in combination for recurrence after withdrawal of VKA in patients enrolled in the PROLONG study. On the day of VKA suspension, the presence of known (coronary, peripheral,cerebral) vascular disease, chronic inflammatory bowel disease, chronic obstructive pulmonary disease, autoimmune disease, diabetes, arterial hypertension, obesity and dyslipidaemias was registered. D-dimer was measured at 30 +/- 10 days afterwards. The primary outcome was recurrent objectively documented VTE. Mean follow-up was 2.55 years. An abnormal D-dimer was observed in 44% (135/309) of patients with comorbidities and in 29% (87/299) of patients without (p=0.0003). An on-treatment analysis was conducted in 483 patients in whom VKAs were not resumed. In patients with a normal D-dimer, recurrences were observed in 14.3% (24/168) of patients with comorbidities and 10.8% (22/203) of subjects without (p=ns). In patients with an abnormal D-dimer, recurrences were observed in 24.6% (16/65) patients with comorbidities and 21.3% (10/47) of patients without (p=ns). Although abnormal D-dimer levels were significantly more frequent in patients with comorbidities, D-dimer was an independent risk factor for recurrence and the presence of comorbidities did not increase the risk of recurrence associated with an abnormal post-anticoagulation D-dimer. PMID- 20352168 TI - Platelet function testing and risk of bleeding complications. AB - Antiplatelet therapy has a key role in preventing atherothrombotic events in patients with coronary artery disease, particularly in those undergoing revascularisation procedures. However, this may occur at the expense of an increase risk of bleeding. Therefore, the balance between thrombotic and bleeding events is critical in order to achieve optimal outcomes. Since there is a broad variability in individual response profiles to antiplatelet therapy, these outcomes (thrombosis vs. bleeding) may depend on the level of platelet inhibition achieved in a given subject. Platelet function assays have emerged as a useful tool for its potential to determine patients at a higher risk of ischaemic and bleeding complications. The present manuscript will review the available evidence associating platelet function testing with adverse clinical outcomes, in particular bleeding, and their potential applications in lieu of novel and more potent antithrombotic agents that will be introduced into clinical practice in the near future. PMID- 20352169 TI - Acute coronary syndrome and severe haemophilia: an unusual association with challenging treatment. PMID- 20352170 TI - Essential thrombocythaemia in a teenage girl resulting in acquired von Willebrand syndrome with joint haemorrhage and menorrhagia. PMID- 20352171 TI - Rare thromboses of cerebral, splanchnic and upper-extremity veins. A narrative review. AB - Venous thrombosis typically involves the lower extremity circulation. Rarely, it can occur in the cerebral or splanchnic veins and these are the most frightening manifestations because of their high mortality rate. A third site of rare venous thrombosis is the deep system of the upper extremities that, as for the lower extremity, can be complicated by pulmonary embolism and post-thrombotic syndrome. The authors conducted a narrative review focused on clinical manifestations, risk factors, and treatment of rare venous thromboses. Local risk factors such as infections or cancer are frequent in thrombosis of cerebral or portal veins. Upper extremity deep-vein thrombosis is mostly due to local risk factors (catheter- or effort-related). Common systemic risk factors for rare venous thromboses are inherited thrombophilia and oral contraceptive use; chronic myeloproliferative neoplasms are closely associated with splanchnic vein thrombosis. In the acute phase rare venous thromboses should be treated conventionally with low-molecular-weight heparin. Use of local or systemic fibrinolysis should be considered in the case of clinical deterioration in spite of adequate anticoagulation. Anticoagulation with vitamin K-antagonists is recommended for 3-6 months after a first episode of rare venous thrombosis. Indefinite anticoagulation is recommended for Budd-Chiari syndrome, recurrent thrombosis or unprovoked thrombosis and permanent risk factors. In conclusion, the progresses made in the last couple of decades in diagnostic imaging and the broadened knowledge of thrombophilic abnormalities improved the recognition of rare venous thromboses and the understanding of pathogenic mechanisms. However, the recommendations for treatment mainly derive from observational studies. PMID- 20352172 TI - Lessons from the major studies in COPD: problems and pitfalls in translating research evidence into practice. AB - Translating the growing evidence base on COPD management into practice can be challenging and understanding the strengths and weakness of published studies is crucial. Studies should conform to the standards of CONSORT statement; they should be sufficiently powered, participants should be randomised, there should be assignment concealment, and the outcome measures and analyses should be decided in advance. The interpretation of the results may be affected by age and severity inclusion criteria for the study and the exclusion of patients with co morbid illnesses. Whether previous medication is continued or stopped can affect the interpretation of the results. Secondary analyses in sub-groups should be viewed with caution unless pre-specified and accommodated in the trial design and power calculations. Real world observational studies may be confounded by non randomisation of participants but can sometimes yield valuable insights. The way in which the results are presented can influence their interpretation and their magnitude with respect to minimal important differences as well as statistical significance is important. Research help formulate management algorithms but often the questions they address are too specific to allow evidence-based sequencing of therapies. PMID- 20352173 TI - Fitness, work, and leisure-time physical activity and ischaemic heart disease and all-cause mortality among men with pre-existing cardiovascular disease. AB - OBJECTIVE: Our aim was to study the relative impact of physical fitness, physical demands at work, and physical activity during leisure time on ischaemic heart disease (IHD) and all-cause mortality among employed men with pre-existing cardiovascular disease (CVD). METHOD: We carried out a 30-year follow-up of the Copenhagen Male Study of 274 gainfully employed men, aged 40-59 years who had a history of CVD (ie, myocardial infarction, angina pectoris, and intermittent claudication). We estimated physical fitness [maximal oxygen consumption (VO (2)Max)] using the Astrand cycling test and determined physical work demands and leisure-time physical activity using a self-reported questionnaire. Results Among 274 men with a history of CVD, 93 men died from IHD. Using male employees with a history of CVD and a low level of fitness as the reference group, our Cox analyses - adjusted for age, blood pressure, smoking, alcohol consumption, body mass index, diabetes, hypertension, physical work demands, leisure-time physical activity, and social class - showed a substantially reduced risk for IHD mortality among employees who were intermediately fit [VO (2)Max range 25-36; hazard ratio (HR) 0.54, 95% confidence interval (95% CI) CI 0.32-0.93] and highly fit (VO (2)Max range 37-50; HR 0.28, 95% CI 0.12-0.66). We found a positive, but statistically non-significant association between physical demands at work and all-cause mortality. CONCLUSION: Among gainfully employed men with pre-existing CVD, a high physical fitness was associated with a substantially reduced risk for IHD and all-cause mortality. PMID- 20352174 TI - Physical demands at work, physical fitness, and 30-year ischaemic heart disease and all-cause mortality in the Copenhagen Male Study. AB - OBJECTIVE: No previous long-term prospective studies have examined if workers with low cardiorespiratory fitness have an increased risk of cardiovascular mortality due to high physical work demands. We tested this hypothesis. METHOD: We carried out a 30-year follow-up of the Copenhagen Male Study of 5249 employed men aged 40-59 years. We excluded from follow-up 274 men with a history of myocardial infarction, prevalent symptoms of angina pectoris, or intermittent claudication. We estimated physical fitness [maximal oxygen consumption (VO (2)Max)] using the Astrand cycling test and determined physical work demands with two self-reported questions. RESULTS: In the Copenhagen Male Study, 587 men (11.9%) died due to ischaemic heart disease (IHD). Using men with low physical work demands as the reference group, Cox analyses--adjusted for age, blood pressure, smoking, alcohol consumption, body mass index, diabetes, and hypertension--showed that high physical work demands were associated with an increased risk of IHD mortality in the least fit [VO (2)Max range 15-26, N=892, hazard ratio (HR) 2.04, 95% confidence interval (95% CI) 1.20-3.49] and moderately fit (VO (2)Max range 27-38, N=3037, HR 1.75, 95% CI 1.24-2.46), but not among the most fit men (VO (2)Max range 39-78, N=1014, HR 1.08, 95% CI 0.52 2.17). We found a similar, although slightly weaker, relationship with respect to all-cause mortality. CONCLUSIONS: The hypothesis was supported. Men with low and medium physical fitness have an increased risk of cardiovascular and all-cause mortality if exposed to high physical work demands. Ours observations suggest that, among men with high physical work demands, being physically fit protects against adverse cardiovascular effects. PMID- 20352175 TI - The natural course of carpal tunnel syndrome in a working population. AB - OBJECTIVE: The aim of this study was to assess prevalence, incidence, and persistence of carpal tunnel syndrome (CTS) and associated symptoms over a one year period in a working population. METHODS: We conducted a one-year prospective study of 418 active workers in 12 worksites. Detailed health interviews, psychosocial questionnaires, and electrophysiological studies [ie, nerve conduction velocity (NCV) tests] were conducted at baseline and one-year follow up. Individual-observed exposure assessments of wrist posture, hand activity, and hand forces were conducted. RESULTS: Prevalence of CTS cases at baseline was 10.8% [95% confidence interval (95% CI) 7.8-13.7%] on the dominant side and 6.0% (95% CI 3.7-87.3%) on the non-dominant side; CTS symptoms were 14.1% (95% CI 10.8 17.5%) and 11.0% (95% CI 8.0-14.0%), respectively. Incidence of CTS cases were 7.5% (95% CI 4.8-10.2%) and 5.6% (95% CI 3.3-7.9%), respectively. Higher proportions of subjects with current symptoms or positive electrophysiological test findings at baseline became CTS cases at one year compared to those with neither (28.6% and 13.9%, respectively, versus 0.5%). One-year persistence of CTS case status was 44.4% (95% CI 29.9-59.0%) for the dominant hand and 52.0% (95% CI 32.4-71.6) for non-dominant hand. There were significant differences at baseline between asymptomatic subjects and CTS cases with respect to higher job demands (P=0.027), lower job satisfaction (P=0.036), lower general health (P=0.0009), higher exposure to vibrating hand tool use (P=0.039), and greater time using a forceful power grip (P=0.035) among cases. CONCLUSIONS: CTS symptoms more than positive NCV test results alone appear to predict CTS at one year. Persistence of CTS at one year is high. PMID- 20352176 TI - [Intensive or conventional glucose control in critically ill patients: NICE-SUGAR (The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation Study)]. PMID- 20352177 TI - [Revascularization in patients with type 2 diabetes and coronary artery disease: BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Study Group]. PMID- 20352178 TI - The frontal gland in workers of Neotropical soldierless termites. AB - The presence of the frontal gland is well established in termite soldiers of Rhinotermitidae, Serritermitidae, and Termitidae. It is one of their main defensive adaptations or even an exclusive weapon. The gland was also occasionally reported in alate imagoes, but never in the worker caste. Here, we report the first observation of a frontal gland in workers of several Neotropical and one African species of Apicotermitinae. The ultrastructure of Aparatermes cingulatus and Anoplotermes nr. subterraneus is described in detail. In these two species, the gland is well-developed, functional and consists of class 1 secretory cells. The presence of envelope cells, wrapping the gland, is an unusual feature, as well as the presence of several zonulae adherens, connecting neighbouring glandular cells. The frontal gland of workers is homologous to this organ in soldiers and imagoes, as evidenced by the same position in the head and its connection to the same muscle. However, the defensive role of the frontal gland in workers remains to be confirmed. PMID- 20352179 TI - Field vole (Microtus agrestis) seasonal spacing behavior: the effect of predation risk by mustelids. AB - There are numerous studies showing that predation risk may change different aspects of the behavior of prey, such as habitat use, activity pattern, and foraging. Prey should exhibit the strongest antipredatory response against their most deadly predator. Small mustelids are considered the most important mammalian predators of voles. Nevertheless, there is no general agreement as to whether strong antipredatory reactions exist in natural free-living populations of voles. Here, we studied the field vole Microtus agrestis spatial reaction to high predation risk from small mustelids in the breeding (August) and nonbreeding (October) seasons under natural conditions. Voles were exposed to a caged weasel (Mustela nivalis) and a stoat (Mustela erminea), as well as to the odors of these predators. The reactions of 30 field voles were monitored with radiotelemetry. The field voles were found to display antipredator reactions that varied with season. In the breeding period, in response to predation risk, voles reduced locomotory activity and daily-range size, whereas in the nonbreeding period they did not. Changes in home range position were similar for control and treatment voles, in both the breeding and nonbreeding periods. The results indicate that mustelid predators modify the spatial behavior of small rodents in natural conditions depending on season. This might be a reflection of differences in state-dependent responses to predation from sexually active or inactive individuals. This suggests that the basic antipredatory reaction of voles under high predation risk from small mustelids limits their locomotory activity. PMID- 20352180 TI - Inferring population structure and genetic diversity of broad range of wild diploid alfalfa (Medicago sativa L.) accessions using SSR markers. AB - Diversity analyses in alfalfa have mainly evaluated genetic relationships of cultivated germplasm, with little known about variation in diploid germplasm in the M. sativa-falcata complex. A collection of 374 individual genotypes derived from 120 unimproved diploid accessions from the National Plant Germplasm System, including M. sativa subsp. caerulea, falcata, and hemicycla, were evaluated with 89 polymorphic SSR loci in order to estimate genetic diversity, infer the genetic bases of current morphology-based taxonomy, and determine population structure. Diploid alfalfa is highly variable. A model-based clustering analysis of the genomic data identified two clearly discrete subpopulations, corresponding to the morphologically defined subspecies falcata and caerulea, with evidence of the hybrid nature of the subspecies hemicycla based on genome composition. Two distinct subpopulations exist within each subsp. caerulea and subsp. falcata. The distinction of caerulea was based on geographical distribution. The two falcata groups were separated based on ecogeography. The results show that taxonomic relationships based on morphology are reflected in the genetic marker data with some exceptions, and that clear distinctions among subspecies are evident at the diploid level. This research provides a baseline from which to systematically evaluate variability in tetraploid alfalfa and serves as a starting point for exploring diploid alfalfa for genetic and breeding experiments. PMID- 20352181 TI - A single-nucleotide polymorphism that accounts for allelic variation in the Lr34 gene and leaf rust reaction in hard winter wheat. AB - Leaf rust, caused by Puccinia triticina Eriks, is one of the most common and persistent wheat diseases in the US Great Plains. We report that the Lr34 gene was mapped in the center of a QTL for leaf rust reaction and explained 18-35% of the total phenotypic variation in disease severity of adult plants in a Jagger x 2174 population of recombinant inbred lines (RILs) field-tested for 3 years. The sequence of the complete Lr34 gene was determined for the susceptible Jagger allele and for the resistant 2174 allele. The two alleles had exactly the same sequence as the resistant allele reported previously in Chinese Spring at three polymorphic sites in intron 4, exon 11, and exon 12. A G/T polymorphism was found in exon 22, where a premature stop codon was found in the susceptible Jagger allele (Lr34E22s), confirming a previous report, due to a point mutation compared with the resistant 2174 allele (Lr34E22r). We have experimentally demonstrated a tight association between the point mutation at exon 22 of Lr34 and leaf rust susceptibility in a segregating biparental population. A PCR marker was developed to distinguish between the Lr34E22r and Lr34E22s alleles. A survey of 33 local hard winter wheat cultivars indicated that 7 cultivars carry the Lr34E22s allele and 26 cultivars carry the Lr34E22r allele. This study significantly improves our genetic understanding of allelic variation in the Lr34 gene and provides a functional molecular tool to improve leaf rust resistance in a major US wheat gene pool. PMID- 20352183 TI - Arsenic in the hair of the individuals in Santana-AP-Brazil: significance of residence location. AB - The concentration of arsenic in the hair of the individuals living in Santana city was measured. 121 donors in urban and the periphery area were studied. The periphery of the city shows the highest levels of arsenic (5.94 +/- 6.54 mg kg( 1) - mean; 0.27-23.85 mg kg(-1)). 47.83% in the urban area showed arsenic concentrations of less than 1.00 mg kg(-1), while in the periphery only 11.22% had results below this value. The results showing the influence of residence location. The Principal Component Analysis showed that the variable residence location were responsible for the correct formation of the periphery group. PMID- 20352182 TI - Fine-mapping of the leaf rust Lr34 locus in Triticum aestivum (L.) and characterization of large germplasm collections support the ABC transporter as essential for gene function. AB - Leaf rust resistance gene Lr34 is likely the most important leaf rust gene characterized to date. It has been characterized as an adult plant resistance gene and is known to enhance the resistance of other leaf rust resistance genes and to condition resistance to a number of other diseases. Located on chromosome 7D, this gene was identified to be one of six co-located genes of which, an ABC transporter was shown to be the only valid candidate. Ten new molecular markers were developed spanning the Lr34 locus, including six novel microsatellite markers (cam), one insertion site-based polymorphism marker (caISBP), two single nucleotide polymorphisms (caSNP), and one gene-specific marker (caIND). Using these new markers and others that were previously published, a comparative fine map of the locus was constructed from five segregating populations representing 1,742 lines. Identification of a susceptible line with a recombination in the 4.9 kb interval between caSNP4 located in the ABC transporter gene and cam8 located just upstream of this gene provided further evidence to support the identity of the ABC transporter as Lr34 by ruling out four of the adjacent genes. Originally, three mutations forming two haplotypes had been described for the ABC transporter gene. A third combination of the three mutations and an additional rare mutation in exon 22 were subsequently described. We identified an additional novel mutation in exon 10 that would cause a frameshift and is likely non-functional. This mutation was only found in Lr34- lines and constituted a novel molecular haplotype. Characterization of two germplasm collections of 700 Triticum aestivum lines permitted us to gain an understanding of the frequency of the ABC haplotypes characterized to date and their distribution in germplasm from and around the world. In addition to the four haplotypes previously described, a fifth haplotype was found in two of the 700 lines from the germplasm collections. These lines displayed the deletion in indel 11 characteristic of Lr34+ lines, but are likely susceptible to leaf rust. Mapping and haplotyping data suggest that of all the markers described herein, marker caIND11 is the best diagnostic marker for marker-assisted selection of Lr34 because it is co-dominant, robust and with the exception of 2/700 lines, it is highly diagnostic. Other markers are also described to provide alternatives for laboratories with different technologies. PMID- 20352184 TI - Mercury and selenium bioaccumulation in the smooth hammerhead shark, Sphyrna zygaena Linnaeus, from the Mexican Pacific Ocean. AB - We analyzed total mercury and selenium bioaccumulation in muscle tissue and cartilage fibers (fins) from smooth hammerhead shark, Sphyrna zygaena, caught off Baja California Sur, Mexico. In muscle tissue, the mercury concentration ranged from 0.005 to 1.93 microg g(-1) ww (wet weight), which falls within the safety limits for food set by international agencies (Hg > 1.0 microg g(-1) ww). Only one specimen showed a mercury value that exceeded this limit. In fins, the mercury bioaccumulation was lower (<0.05). Selenium in muscle ranged from 0.11 to 1.63 microg g(-1) ww, while in fins it ranged from 0.13 to 0.56 microg g(-1) ww. PMID- 20352185 TI - Soil test phosphorus as an indicator of nitrate-nitrogen leaching risk in tile drainage water. AB - A 2 year tile drainage study of 39 fields in Nova Scotia, Canada was conducted. Weekly nitrate-nitrogen (NO(3)-N) concentrations were highest in spring and fall during high flow. Fields receiving poultry or swine manure had elevated drainage NO(3)-N and soil test phosphorus. Water quality guidelines for NO(3)-N (10 mg L( 1)) were exceeded on 90% of rotations (corn-grass or corn-grain) and 13% of long term cover fields. A significant correlation between NO(3)-N and soil test P (r (2) = 0.42; p < 0.001) was found. The 10 mg L(-1) guideline was exceeded at 100% of fields with soil test phosphorus >200 mg kg(-1) and 60% overall. PMID- 20352186 TI - Accelerated metolachlor degradation in soil by zerovalent iron and compost amendments. AB - Soil incubation and germination tests were conducted to assess zerovalent iron (ZVI), organic compost, moisture and their combinations on metolachlor degradation in soil. The ZVI alone degraded 91% of metolachlor in soil within 40 days following bi-phasic kinetics. Organic amendment alone facilitated metolachlor degradation in soil up to 60% after 40 days depending on the amendment rate. However, the combination of ZVI with compost amendment at 30 ton ha(-1) and 30% moisture content accelerated metolachlor degradation to 90% after 3 days and 98% after 40 days. The half life (t (1/2)) of metolachlor degradation with ZVI, compost at 30 ton ha(-1), and 30% moisture was about 1 day, which was faster than ZVI treatment alone and 98% faster than controls. Germination and growth of lettuce (Lactuca sativa) and crabgrass (Digitaria sanguinalis L. Scop.) were severely inhibited in unamended metolachlor-contaminated soils but when these soils were amended with ZVI, germination and growth was comparable to controls (metolachlor free soil). Metolachlor degradation was greatest when ZVI, compost and moisture were used together, suggesting that these treatments will maximize in situ remediation of metolachlor-contaminated soils in the field. PMID- 20352187 TI - Boron concentration in water, sediment and different organisms around large borate deposits of Turkey. AB - Boron is an essential nutrient for plants and an essential element for many organisms, but can be toxic to aquatic and terrestrial organisms above certain concentrations. The aim of this research was to determine boron concentrations in water, sediment and biotic samples (Gammaridae spp.-Crustacea, Helix sp. Gastropoda, Donax sp.-Bivalvia, Helobdella sp.-Hirudinae, Ephemeroptera nymph, Chrinomidae larvae, Tipulidae larvae-Insecta, Rana sp.-Amphibia, Natrix sp. Serpentes, fish sample Leiscus cephalus (Linnaeus, 1758) and leaves of Salix sp. Salicacea from Seydi Stream (Kirka-Eskisehir). Our results have shown that boron concentrations of the Seydi Stream water is higher than the Turkish Environmental Guidelines standard (>1 mg L(-1)) and in Europe (mean values typically below 0.6 mg L(-1)). PMID- 20352188 TI - Determination of endocrine disrupting chemicals in surface water and industrial wastewater from Beijing, China. AB - An analytical method was developed for determination of some endocrine-disrupting chemicals in water samples from Beijing, China. Fifty two surface water and 50 industrial wastewater samples were analyzed. The residue was detected in 26 industrial wastewater and 19 surface water samples. Atrazine was detected in 8 samples at different levels ranging from 0.12 to 5.16 microg L(-1), and phenolic compounds were detected in 19 samples ranging from 0.8 to 26.1 microg L(-1). The results show that the main pollutants of surface water samples were atrazine and octylphenol. In industrial wastewater samples, bisphenol A and octylphenol were most commonly found. PMID- 20352189 TI - Physiological comparison of three spontaneous breathing trials in difficult-to wean patients. AB - PURPOSE: To compare cardiovascular and respiratory responses to different spontaneous breathing trials (SBT) in difficult-to-wean patients using T-piece and pressure support ventilation (PSV) with or without positive end-expiratory pressure (PEEP). METHODS: Prospective physiological study. Fourteen patients who were monitored with a Swan-Ganz catheter and had failed a previous T-piece trial were studied. Three SBTs were performed in random order in all patients: PSV with PEEP (PSV-PEEP), PSV without PEEP (PSV-ZEEP), and T-piece. PSV level was 7 cmH(2)O, and PEEP was 5 cmH(2)O. Inspiratory muscle effort was calculated, and hemodynamic parameters were measured using standard methods. RESULTS [MEDIAN (AND INTERQUARTILE RANGE)]: Most patients succeeded in the PSV-PEEP (11/14) and PSV ZEEP (8/14) trials, but all failed the T-piece trial. Patient effort was significantly higher during T-piece than during PSV with or without PEEP [esophageal pressure-time product was 292 (238-512), 128 (58-299), and 148 (100 465) cmH(2)O x s/min, respectively, p < 0.05]. Left ventricular heart failure was observed in 11 of the 14 patients during the T-piece trial. Pulmonary artery occlusion pressure and respiratory rate were significantly higher during T-piece than with PSV-PEEP [21 (18-24) mmHg versus 17 (14-22) mmHg, p < 0.05 and 27 (21 35) breaths/min versus 19 (16-29) breaths/min, p < 0.05 respectively]. Tidal volume was significantly lower during the T-piece trial. CONCLUSION: In this selected population of difficult-to-wean patients, PSV and PSV plus PEEP markedly modified the breathing pattern, inspiratory muscle effort, and cardiovascular response as compared to the T-piece. Caregivers should be aware of these differences in SBT as they may play an important role in weaning decision-making. PMID- 20352190 TI - Effects of blood glucose transcription mismatches on a computer-based intensive insulin therapy protocol. AB - PURPOSE: Computerized clinical decision support systems (CDSS) for intensive insulin therapy (IIT) generate recommendations using blood glucose (BG) values manually transcribed from testing devices to computers, a potential source of error. We quantified the frequency and effect of blood glucose transcription mismatches on IIT protocol performance. METHODS: We examined 38 months of retrospective data for patients treated with CDSS IIT in two intensive care units at one teaching hospital. A manually transcribed BG value not equal to a corresponding device value was deemed mismatched. For mismatches we recalculated CDSS recommendations using device BG values. We compared matched and mismatched data in terms of CDSS alerts, blood glucose variability, and dosing. RESULTS: Of 189,499 CDSS IIT instances, 5.3% contained mismatched BG values. Mismatched data triggered 93 false alerts and failed to issue 170 alerts for nurses to notify physicians. Four of six BG variability measures differed between matched and mismatched data. Overall insulin dose was greater for matched than mismatched [matched 3.8 (1.6-6.0), median (interquartile range, IQR), versus 3.6 (1.6-5.7); p < 0.001], but recalculated and actual dose were similar. In mismatches preceding hypoglycemia, recalculated insulin dose was significantly lower than actual dose [recalculated 2.7 (0.4-5.0), median (IQR), versus 3.5 (1.4-5.6)]. In mismatches preceding hyperglycemia, recalculated insulin dose was significantly greater than actual dose [recalculated 4.7 (3.3-6.2), median (IQR), versus 3.3 (2.4-4.3); p < 0.001]. Administration of recalculated doses might have prevented blood glucose excursions. CONCLUSIONS: Mismatched blood glucose values can influence CDSS IIT protocol performance. PMID- 20352192 TI - Corticosteroids for H1N1 associated acute lung injury: is it just wishful thinking? PMID- 20352193 TI - Hydrocortisone therapy for patients with H1N1 influenza A infection. PMID- 20352194 TI - The adjustable tension-free vaginal tape--obturator. AB - A 59-year-old woman presented with stress urinary incontinence, had adjustment of tension-free vaginal tape-obturator (TVT-O) performed using a method that does not require lateral dissection, after a failed TVT-O. Despite having TVT-O tape erosion, she has remained continent for a period of 24 months. The case demonstrates an effective and simple method of TVT-O tape readjustment. PMID- 20352195 TI - Beauvericin and ochratoxin A genotoxicity evaluated using the alkaline comet assay: single and combined genotoxic action. AB - This study was aimed at investigating the genotoxic potential of single beauvericin (BEA) and ochratoxin A (OTA) as well as their interaction in porcine kidney epithelial PK15 cells and human leukocytes using the alkaline comet assay. IC(50) of BEA (5.0 +/- 0.6) and OTA (15.8 +/- 1.5) estimated by MTT reduction assay shows that BEA is three times more toxic than OTA. BEA (0.1 and 0.5 microM) and OTA (1 and 5 microM) were applied alone or in combination of these concentrations for 1 and 24 h in PK15 cells and human leukocytes. Genotoxicity of these toxins to PK15 cells was time- and concentration dependent. After 1 h, significant increase in tail length, tail intensity, tail moment, and abnormal sized tails (AST) was noted upon exposure to 1 muM of OTA alone and BEA + OTA combinations. Single BEA (0.5 microM) and OTA (1 and 5 microM) and their combinations evoked significant DNA damage in PK15 cells, considering all comet tail parameters measured after 24 h of treatment. Human leukocytes were slightly concentration but not time dependent. After 1 h of exposure, there were no significant changes in the tail length. Tail intensity, tail moment, and/or incidence of AST were significantly higher in cells treated with single OTA or BEA and their combinations than in control cells. DNA damage in leukocytes was significantly higher after 24 h of exposure to single toxins and their combinations, considering all comet tail parameters, but these changes were less pronounced than in PK15 cells. Combined toxins showed additive and synergistic effects in PK15 cells, while only additive effects were observed in human leukocytes. Combined prolonged exposure to BEA and OTA in subcytotoxic concentrations through food consumption could induce DNA damage contributing to the carcinogenicity in animals and humans. PMID- 20352197 TI - Cytometric methods for measuring bacteria in water: advantages, pitfalls and applications. AB - Rapid detection of microbial cells is a challenge in microbiology, particularly when complex indigenous communities or subpopulations varying in viability, activity and physiological state are investigated. Flow cytometry (FCM) has developed during the last 30 years into a multidisciplinary technique for analysing bacteria. When used correctly, FCM can provide a broad range of information at the single-cell level, including (but not limited to) total counts, size measurements, nucleic acid content, cell viability and activity, and detection of specific bacterial groups or species. The main advantage of FCM is that it is fast and easy to perform. It is a robust technique, which is adaptable to different types of samples and methods, and has much potential for automation. Hence, numerous FCM applications have emerged in industrial biotechnology, food and pharmaceutical quality control, routine monitoring of drinking water and wastewater systems, and microbial ecological research in soils and natural aquatic habitats. This review focuses on the information that can be gained from the analysis of bacteria in water, highlighting some of the main advantages, pitfalls and applications. PMID- 20352196 TI - Substitution of the Walker A lysine by arginine in the nucleotide-binding domains of sulphonylurea receptor SUR2B: effects on ligand binding and channel activity. AB - Sulphonylurea receptors (SURs) serve as regulatory subunits of ATP-sensitive K(+) channels. SURs are members of the ATP-binding cassette (ABC) protein superfamily and contain two conserved nucleotide-binding domains (NBDs) which bind and hydrolyse MgATP; in addition, they carry the binding sites for the sulphonylureas like glibenclamide (GBC) which close the channel and for the K(ATP) channel openers such as P1075. Here we have exchanged the conserved Lys in the Walker A motif by Arg in both NBDs of SUR2B, the regulatory subunit of the vascular K(ATP) channel. Then the effect of the mutation on the ATPase-dependent binding of GBC and P1075 to SUR2B and on the activity of the recombinant vascular (Kir6.1/SUR2B) channel was assessed. Surprisingly, in the absence of MgATP, the mutation weakened binding of P1075 and the extent of allosteric inhibition of GBC binding by P1075. The mutation abolished most, but not all, of the MgATP effects on the binding of GBC and P1075 and prevented nucleotide-induced activation of the channel which relies on SUR reaching the posthydrolytic (MgADP-bound) state; the mutant channel was, however, opened by P1075 at higher concentrations. The data provide evidence that mutant SUR2B binds MgATP but that the posthydrolytic state is insufficiently populated. This suggests that the mutation locks SUR2B in an MgATP-binding prehydrolytic-like state; binding of P1075 may induce a posthydrolytic-like conformation to open the channel. PMID- 20352198 TI - Capillary liquid chromatography with off-line mid-IR and Raman micro spectroscopic detection: analysis of chlorinated pesticides at ppb levels. AB - A flow-through microdispenser was used as a solvent elimination interface, allowing vibrational spectroscopic detection in capillary liquid chromatography in addition to standard UV detection. Using a flow-through microdispenser, robust and stable deposition of picoliter-sized droplets on a CaF(2) plate window was achieved. The CaF(2) window was placed on a thermostated sample holder (80 degrees C) mounted on a computerized x, y stage for achieving fast solvent evaporation and enabling recording of the chromatogram as a trace of deposited material. The dried residues that were formed had diameters of a few tens of micrometers and were analysed by mid-IR and Raman micro-spectroscopy. Conditions were optimized for high sensitivity of measurement and maintaining chromatographic resolution during the deposition step. Due to the destruction free character of Raman and FTIR spectroscopy, these techniques could be applied sequentially to interrogate the same deposits. To test the usefulness of the methodology for environmental analysis, the determination and unambiguous identification of chlorinated pesticides (chlortoluron, diuron, atrazine, and terbuthylazine) in river water was used as an example, obtaining limits of identification of 2 ng analyte on-column and precision of approximately 10% RSD. The application of the developed method to spiked real river samples demonstrated the identification power of the proposed method as, in addition to the four previously studied pesticides, two additional pesticides (simazine and isoproturon) could also be detected and identified. PMID- 20352199 TI - Age-related differences in force variability and visual display. AB - It is well established that older adults are more variable in their force output and that this age-related decrement is mediated by visuomotor processing. The purpose of this investigation was to examine whether the type of visual display impacts age-related differences in the control of force output. In order to address this question, young and old participants produced constant isometric force via index finger abduction to 3 force levels [5, 10, and 20% of their maximal voluntary contraction (MVC)]. Visual feedback was presented with either a compensatory or a pursuit display. A compensatory display provides visual feedback about force amplitude in relation to the criterion target whereas a pursuit display provides visual feedback about the force trajectory in relation to the criterion target and preview of the target path of the force trajectory. The magnitude of force variability was indexed with standard deviation and coefficient of variation. The structure of force output was indexed with spectral slope and approximate entropy. As expected, older adults were more variable and had more structured force output compared to younger adults. Moreover, this age related difference in force control was paramount in pursuit displays. Overall, the findings suggest that age-related differences in force control are centrally mediated. It is proposed that older adults have deficits in visuomotor processing and this may be partly related to age-related decrements in the control of eye movements. PMID- 20352200 TI - Predicting the position of moving audiovisual stimuli. AB - Predicted motion (PM) tasks test the accuracy of predicting the future position of a moving target. Previous PM studies using audiovisual stimuli have suggested that observers rely primarily on visual motion cues. To clarify the role of auditory signals in predicting future positions of bimodal targets, we designed a novel PM task where spatial coincidence of audio and visual motion signals was varied in three conditions: auditory and visual motion stimuli were spatially correlated (congruent condition), the auditory motion stimulus was moving behind the visual motion stimulus (sound-trailing condition), or the auditory motion stimulus was moving ahead the visual motion stimulus (sound-leading condition). We manipulated target speed (5.5 or 11 cm/s), the time that the moving audiovisual stimulus was presented (500 or 750 ms viewing time), and the time the visual stimulus disappeared while the auditory stimulus continued to move by itself before prompting subjects to estimate the position of the visual stimulus would have traveled if it continued along with the auditory stimulus (750, 1,000, or 1,500 ms prediction time). We also included two unimodal control conditions: visual-only and auditory-only. Subjects (n = 12) typically overestimated the target position of congruent bimodal targets. In the sound-trailing and sound leading conditions, pointing responses were biased in the direction of the auditory stimulus, showing that PM performance is not reliant solely upon visual motion cues. We conclude that putative cognitive extrapolation mechanisms assume spatial coherence of bimodal motion signals and may perform some averaging of these motion signals when they do not spatially coincide. PMID- 20352201 TI - Motion-onset auditory-evoked potentials critically depend on history. AB - The aim of the present study was to determine whether motion history affects motion-onset auditory-evoked potentials (motion-onset AEPs). AEPs were recorded from 33 EEG channels in 16 subjects to the motion onset of a sound (white noise) virtually moving in the horizontal plane at a speed of 60 deg/s from straight ahead to the left (-30 degrees ). AEPs for baseline and adaptation were compared. A stimulus trial comprised three consecutive phases: 2,000 ms adaptation phase, 1,000 ms stationary phase, and 500 ms test phase. During the adaptation phase of the adaptation condition, a sound source moved twice from +30 degrees to -30 degrees to top up preceding adaptation. In the baseline condition, neither top-up nor pre-adaptation were exerted. For both conditions, a stationary sound was presented centrally in the stationary phase, moving leftwards in the test phase. Typical motion-onset AEPs were obtained for the baseline condition, namely a fronto-central response complex dominated by a negative and a positive component, the so-called change-N1 and change-P2 after around 180 and 250 ms, respectively. For the adaptation condition, this complex was shifted significantly into the positive range, indicating that adaptation abolished a negativity within a time window of approximately 160 to 270 ms. A respective shift into the negative range was evident at occipito-parietal sites. In conclusion, while adaptation has to be taken into account as a potential confound in the design of motion-AEP studies, it might also be of benefit in order to isolate AEP correlates of motion processing. PMID- 20352202 TI - The role of phosphatidic acid and cardiolipin in stability of the tetrameric assembly of potassium channel KcsA. AB - In this study, the roles of two anionic phospholipids-phosphatidic acid (PA), which is an important signaling molecule, and cardiolipin (CL), which plays a crucial role in the bioenergetics of the cell-in stabilizing the oligomeric structure of potassium channel KcsA were determined. The stability of KcsA was drastically increased as a function of PA or CL content (mol%) in phosphatidylcholine (PC) bilayers. Deletion of the membrane-associated N terminus significantly reduced channel stability at high levels of PA content; however, the intrinsic stability of this protein was marginally affected in the presence of CL. These studies indicate that the electrostatic-hydrogen bond switch between PA and N terminus, involving basic residues, is much stronger than the stabilizing effect of CL. Furthermore, the unique properties of the PA headgroup alter protein assembly and folding properties differently from the CL headgroup, and both lipids stabilize the tetrameric assembly via their specific interaction on the extra- or the intracellular side of KcsA. PMID- 20352203 TI - Nonneuronal cholinergic system in human erythrocytes: biological role and clinical relevance. AB - Acetylcholine is well known in the medical setting as one of the most exemplary neurotransmitters. Its ubiquity in nature otherwise suggests a theoretically diverse spectrum of action and an extremely early appearance in the evolutionary process. In humans, acetylcholine and its synthesizing enzyme, choline acetyltransferase, have been found in various nonneural tissues such as the epithelium, mesothelium, endothelium, muscle, immune cells and blood cells. The widespread expression of nonneuronal acetylcholine is accompanied by the ubiquitous presence of acetylcholinesterase and nicotinic/muscarinic receptors. Structural and functional dissimilarities are evident between the nonneuronal and neuronal cholinergic systems. An increasing body of evidence throughout the last few years has placed acetylcholine as a major cellular signaling molecule in many pathways. Furthermore, numerous erythrocyte physiological events in the microcirculation are strongly regulated by acetylcholine. Thus, it is time to revise our understanding of the role of vascular acetylcholine in humans. Its biological and pathobiological roles must be evaluated in more detail to eventually achieve novel therapeutical targets. The present article reviews recent findings about nonneuronal acetylcholine in red blood cells, with special regard to (1) red cell rheology, (2) plasma ion concentrations, (3) nitric oxide intracellular translocation and metabolism and (4) band 3 protein phosphorylation. PMID- 20352204 TI - Organochlorine pesticides in consumer fish and mollusks of Liaoning province, China: distribution and human exposure implications. AB - Fish and mollusk samples were collected from markets located in 12 cities in Liaoning province, China, during August and September 2007, and 22 organochlorine pesticides (OCPs) were detected. DDT, HCH, endosulfan, chlordane, and HCB were the dominating OCPs, with mean concentrations and ranges of, respectively, 15.41 and 0.57 to 177.56 ng/g, 0.84 and below detection limit (BDL) to 22.99 ng/g, 1.31 and BDL to 13.1 ng/g, 1.05 and BDL to 15.68 ng/g, and 0.63 and BDL to 9.21 ng/g in all fish and mollusk samples. The concentrations of other OCPs generally were low and were detectable in a minority of samples, reflecting the low levels of these OCPs in the study region. In general, OCP concentrations were obviously higher in fish than in mollusks, and higher in freshwater fish than in marine fish, which indicated, first, that freshwater fish are more easily influenced than seawater fish and mollusks by OCP residues in agricultural areas and, second, that there are different biota accumulation factors for OCPs between fish and mollusk. To learn the consumption of fish and mollusk, 256 questionnaires were sent to families in 12 cities of Liaoning province. Using the contamination data, average estimated daily intakes of OCPs via fish and mollusk consumption were calculated, which were used for exposure assessment. The public health risks caused by exposure to OCPs in the course of fish and mollusk consumption were compared to noncancer benchmarks and cancer benchmarks. PMID- 20352205 TI - Genetic diversity and structure of Neotyphodium species and their host Achnatherum sibiricum in a natural grass-endophyte system. AB - Achnatherum sibiricum (Poaceae) is a perennial bunchgrass native to the Inner Mongolia Steppe of China. This grass is commonly infected by epichloe endophytes with high-infection frequencies. Previously, we identified two predominant Neotyphodium spp., N. sibiricum and N. gansuense. In the present study, genetic diversity and structure were analyzed for the two predominant Neotyphodium spp. as well as the host grass. We obtained 103 fungal isolates from five populations; 33 were identified as N. sibiricum and 61 as N. gansuense. All populations hosted both endophytic species, but genetic variation was much higher for N. gansuense than for N. sibiricum. The majority of fungal isolates were haploid, and 13% of them were heterozygous at one SSR locus, suggesting hybrid origins of those isolates. Significant linkage disequilibrium of fungal SSR loci suggested that both fungal species primarily propagate by clonal growth through plant seeds, whereas variation in genetic diversity and the presence of hybrids in both endophytic species revealed that although clonal propagation was prevalent, occasional recombination might also occur. By comparing genetic differentiation among populations, we found around 4-7-fold greater differentiation of endophyte populations than host populations, implying more restricted gene flow of endophytes than hosts. We proposed that endophyte infection of A. sibiricum might confer the host some selective advantages under certain conditions, which could help to maintain high-endophyte-infection frequencies in host populations, even when their gene flows do not match each other. Furthermore, we suggested that the same genotype of endophyte as well as host should be confirmed if the objective of the study is to know the influence of endophyte or host genotype on their symbiotic relationship, instead of just considering whether the plant is infected by an endophyte or not, since endophytes from the same host species could exhibit high levels of genetic diversity, which is likely to influence the outcome of their symbiotic relationship. PMID- 20352206 TI - In situ dynamics and spatial heterogeneity of soil bacterial communities under different crop residue management. AB - The effect of the location of wheat residues (soil surface vs. incorporated in soil) on their decomposition and on soil bacterial communities was investigated by the means of a field experiment. Bacterial-automated ribosomal intergenic spacer analysis of DNA extracts from residues, detritusphere (soil adjacent to residues), and bulk soil evidenced that residues constitute the zone of maximal changes in bacterial composition. However, the location of the residues influenced greatly their decomposition and the dynamics of the colonizing bacterial communities. Sequencing of 16S rRNA gene in DNA extracts from the residues at the early, middle, and late stages of degradation confirmed the difference of composition of the bacterial community according to the location. Bacteria belonging to the gamma-subgroup of proteobacteria were stimulated when residues were incorporated whereas the alpha-subgroup was stimulated when residues were left at the soil surface. Moreover, Actinobacteria were more represented when residues were left at the soil surface. According to the ecological attributes of the populations identified, our results suggested that climatic fluctuations at the soil surface select populations harboring enhanced catabolic and/or survival capacities whereas residues characteristics likely constitute the main determinant of the composition of the bacterial community colonizing incorporated residues. PMID- 20352207 TI - Bacterial community associated with healthy and diseased reef coral Mussismilia hispida from eastern Brazil. AB - In order to characterize the bacterial community diversity associated to mucus of the coral Mussismilia hispida, four 16S rDNA libraries were constructed and 400 clones from each library were analyzed from two healthy colonies, one diseased colony and the surrounding water. Nine bacterial phyla were identified in healthy M. hispida, with a dominance of Proteobacteria, Actinobacteria, Acidobacteria, Lentisphaerae, and Nitrospira. The most commonly found species were related to the genera Azospirillum, Hirschia, Fabibacter, Blastochloris, Stella, Vibrio, Flavobacterium, Ochrobactrum, Terasakiella, Alkalibacter, Staphylococcus, Azospirillum, Propionibacterium, Arcobacter, and Paenibacillus. In contrast, diseased M. hispida had a predominance of one single species of Bacteroidetes, corresponding to more than 70% of the sequences. Rarefaction curves using evolutionary distance of 1% showed a greater decrease in bacterial diversity in the diseased M. hispida, with a reduction of almost 85% in OTUs in comparison to healthy colonies. integral-Libshuff analyses show that significant p values obtained were <0.0001, demonstrating that the four libraries are significantly different. Furthermore, the sympatric corals M. hispida and Mussismilia braziliensis appear to have different bacterial community compositions according to Principal Component Analysis and Lineage-specific Analysis. Moreover, lineages that contribute to those differences were identified as alpha-Proteobacteria, Bacteroidetes, and Firmicutes. The results obtained in this study suggest host microbe co-evolution in Mussismilia, and it was the first study on the diversity of the microbiota of the endemic and endangered of extinction Brazilian coral M. hispida from Abrolhos bank. PMID- 20352208 TI - Is conflict of interest in our best interest? PMID- 20352209 TI - Doctor, what does my future hold? The prognostic value of FDG-PET in solid tumours. PMID- 20352210 TI - Preoperative [18F]FDG PET/CT maximum standardized uptake value predicts recurrence of uterine cervical cancer. AB - PURPOSE: To determine if preoperative [(18)F]FDG-PET/CT imaging has prognostic significance in patients with uterine cervical cancer. METHODS: Patients with FIGO stage IB to IIA cervical cancer were imaged with integrated FDG PET/CT before radical surgery. The relationship between the maximum standardized uptake value (SUV(max)) of FDG in the primary tumour during PET/CT and recurrence was examined. RESULTS: Included in the study were 75 patients. Medical records including clinical data, treatment modalities, and treatment results were retrospectively reviewed. The median duration of follow-up was 13 months (range 3 to 58 months) after treatment. Median preoperative SUV(max) values in the primary tumours were significantly higher in patients with higher FIGO stages (p = 0.0149), pelvic lymph node metastasis (p = 0.0068), parametrial involvement (p = 0.0002), large (>4 cm) tumour size (p = 0.0022), presence of lymphovascular space invasion (p = 0.0055), and deep cervical stromal invasion (p < 0.0001). In univariate analysis, lymph node metastasis, parametrial invasion, presence of lymphovascular space invasion, and preoperative SUV(max) (uncategorized values) in the primary tumour were significantly associated with recurrence. However, in multivariate analysis, preoperative SUV(max) (p = 0.014, HR 1.178, 95% CI 1.034 1.342), age (p = 0.021, HR 0.87, 95% CI 0.772-0.980), and parametrial involvement (p = 0.040, HR 27.974, 95% CI 1.156-677.043) by primary tumour were significantly associated with recurrence. CONCLUSION: Preoperative FDG uptake by the primary tumour showed a significant association with recurrence in patients with uterine cervical cancer. PMID- 20352211 TI - Infected abdominal aortic aneurysm due to Morganella morganii: CT findings. AB - An infected aortic aneurysm, or mycotic aneurysm, is a rare arterial dilatation due to destruction of the infected vessel wall. Common pathogens resulting in an infected aortic aneurysm are Salmonella and Clostridium species, as well as Staphylococcus aureus; Morganella morganii, on the other hand, is very rare. An infected abdominal aortic aneurysm has tendencies to grow rapidly and to rupture. The mortality rate is high in patients undergoing emergent surgical intervention. We report the case of a 65-year-old man who presented with an infected abdominal aortic aneurysm caused by M. morganii. A high index of suspicion and imaging tests are necessary in order to diagnose an infected aortic aneurysm. PMID- 20352212 TI - Isolates of Citrus tristeza virus that overcome Poncirus trifoliata resistance comprise a novel strain. AB - The economically important rootstock species Poncirus trifoliata is resistant to most isolates of Citrus tristeza virus (CTV), but not to members of the CTV resistance-breaking (RB) strain presently found in New Zealand. In this study, five known and suspected RB isolates were separated from field mixtures, and their genomes were sequenced in full. It was found that the RB isolates are members of a single phylogenetically distinct clade with an average of 90.3% genomic nucleotide sequence identity to the closest extant isolate, T36. These isolates also show evidence of multiple recombination events throughout their evolutionary history, with T36, T30 and VT-like isolates, and with each other. Finally, the genomic sequences of these isolates show that several genes contain unique polymorphisms that may or may not be involved in overcoming resistance. These data will aid in the understanding of host-virus interactions, and the mechanism of resistance in P. trifoliata. PMID- 20352213 TI - Adrenal injury following blunt abdominal trauma. AB - BACKGROUND: Adrenal injury secondary to abdominal trauma is quite rare because the adrenal gland is located deep in the retroperitoneum and is well cushioned by surrounding soft tissues. This report presents our experiences of managing patients with adrenal injury following abdominal blunt trauma. METHODS: The medical records of 11 patients who had been treated for adrenal gland injury between January 1998 and June 2009 were retrospectively reviewed. RESULTS: Of the 11 patients, nine were male and two were female and the mean age was 31.5 years. The causes of trauma were motor vehicle accident (8 cases) and fall (3 cases). The majority of injuries occurred on the right side (8 cases), two were on the left side, and one patient had bilateral injury. Three cases presented as isolated adrenal gland injuries, and eight were combined with other internal organ injuries. The most common coinjured organ was the liver, followed by the kidney. The most useful diagnostic modality was computed tomography (CT). Ten cases were treated successfully using conservative management, while one required a left partial adrenalectomy and splenectomy due to active bleeding. CONCLUSIONS: Adrenal injury due to blunt abdominal trauma is extremely rare. The majority of cases can be diagnosed using CT. Most cases involve the right side and can be treated successfully using conservative management. Surgery is required only in cases of active bleeding. PMID- 20352214 TI - Partial breast reconstruction for an inferomedial breast carcinoma using an omental flap. AB - BACKGROUND: Various oncoplastic techniques are used for partial reconstruction after breast-conserving surgery (BCS), but treatment of an inferomedial breast carcinoma (IMBC) can be difficult, especially in a small breast. We review our experience with immediate partial breast reconstruction after BCS for an IMBC using a laparoscopically harvested omental flap (OF). METHODS: The subjects were 24 patients with an IMBC who underwent immediate partial breast reconstruction with the OF between April 2002 and June 2009. A wide excision (>20% of the breast tissue) was performed through a skin incision along the medial inframammary fold. The pedicled OF was harvested laparoscopically and used to fill the dead space in the inferomedial quadrant. RESULTS: The mean follow-up period was 35 months. The mean tumor size was 3.2 cm. The mean volume of resected breast tissue was 180 g and the mean extent of resection was 40%. The complication rate was 12.5% and all were minor and treated conservatively. Laparoscopy-associated complications did not occur, except for one minor injury of the gastroepiploic artery. The surgical margin was positive in only 1 patient (4.2%) and neither local nor systemic recurrence has occurred to date in any patients. Cosmetic outcomes were mostly satisfactory, with minimal donor-site scars in the abdominal wall. Cosmetic failure occurred in 1 patient (4.2%) due to an inadequate OF volume. CONCLUSIONS: Laparoscopic harvesting of the OF is a safe procedure with minimal donor-site morbidities and deformities. This approach is an option for immediate partial reconstruction after BCS for an IMBC. PMID- 20352215 TI - Traditional versus three-dimensional teaching of peritoneal embryogenesis: a comparative prospective study. AB - INTRODUCTION: Anatomy teaching is newly boosted by the development of interactive three-dimensional (3D) teaching techniques. Nevertheless, their superiority as teaching aids has never been demonstrated. The aim of this study was to compare 3D and traditional chalk teaching efficiency in terms of student memorization concerning peritoneal embryogenesis. MATERIALS AND METHODS: 165 students from the Faculties of Medicine of Sfax (Tunisia) (n = 81) and of Paris-Descartes (France) (n = 84) were taught peritoneal embryogenesis either via a 3D technique (interactive DVD ROM) (3D group, n = 85) or via the traditional chalk technique (CL group, n = 80). Both groups were subjected to an evaluation test including 34 questions distributed in six chapters at the end of the course. RESULTS: The overall rate of correct answers was higher in the 3D group (65.12 +/- 14.88 vs. 49.33 +/- 16.17%, p < 0.001). It was the same for five of the six chapters of questions excluding the chapter concerning the clinical implications (p = 0.06). There was no significant difference between 3D and CL groups regarding the 20 questions focusing on static phenomena (64.52 +/- 27.10 vs. 58.87 +/- 23.67%, p = 0.24), but the rate of correct answers was higher in the 3D group for the 14 questions focusing on dynamic phenomena (65.96 +/- 20.97 vs. 28.17 +/- 24.40%, p < 0.001). CONCLUSION: The 3D technique is significantly more efficient than the traditional chalk technique for the teaching of peritoneal embryogenesis in terms of short-term memorization and particularly for the assimilation of dynamic phenomena. Medium-term and long-term studies are needed to demonstrate that this benefit has a long-lasting impact. PMID- 20352216 TI - Phase II study of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer. AB - PURPOSE: The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer. METHODS: Patients with histologically or cytologically proven, advanced pancreatic cancer who had received first-line chemotherapy with gemcitabine were eligible for this study. S-1 was administered orally at a dose of 40 mg/m(2) twice daily for 28 days, followed by 14 days' rest. Treatment was repeated every 6 weeks until disease progression. RESULTS: Twenty-one patients were enrolled in this study. Grade 3 and 4 toxicities included anorexia in 14% of the patients, abdominal pain in 4.8% and infection without neutropenia in 4.8%. S-1 was discontinued in two patients because of toxicity. Of the 21 eligible patients, 2 (9.5%) achieved a partial response and 9 (43%) had stable disease. A marked decrease (>=50%) in tumor marker (CA19-9) was observed in 5 (28%) of the 18 evaluable patients. The median progression-free survival and the median survival time from the first day of S-1 therapy were 4.1 months (95% CI, 1.3-6.9 months) and 6.3 months (95% CI, 3.6-8.9 months), respectively. CONCLUSIONS: Second-line chemotherapy with S-1 was tolerated with acceptable toxicity and resulted in a relatively high disease control rate in patients with gemcitabine-resistant advanced pancreatic cancer. As an oral agent, S-1 may be a feasible treatment option for this patient population. PMID- 20352217 TI - Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo. AB - PURPOSE: Inflammation plays a crucial role in the development of lung cancer. Accumulated studies have proved that non-steroidal anti-inflammatory drugs (NSAIDs) which block inflammation by their actions on arachidonic acid (AA) metabolism have a potential role in cancer chemotherapy and chemoprevention. The aim of our study was to investigate whether darbufelone, a novel anti inflammatory drug, has anticancer effects in lung cancer. METHODS: Human non small cell lung cancer cell lines were treated with darbufelone at various doses and time points for analysis of cell viability, cell cycle, and apoptosis in vitro. The in vivo effect of darbufelone was assessed in Lewis lung carcinoma mice model. RESULTS: Darbufelone inhibited the proliferation of non-small cell lung cancer cell lines in a dose-dependent manner, and induced cell cycle arrest at G0/G1 phase through up-regulation of p27 expression. Treatment with darbufelone also induced apoptosis by activating caspase-3 and caspase-8. Lewis lung carcinoma growth was also significantly inhibited by darbufelone treatment at daily dose of 80 mg/kg. CONCLUSIONS: Taken together, these studies suggested that darbufelone, an anti-inflammation drug, might represent a novel therapeutic approach for lung cancer treatment. PMID- 20352218 TI - Antisynthetase syndrome associated with long-standing rheumatoid arthritis. PMID- 20352219 TI - The turnover of synovial T cells is higher than in T cells in the peripheral blood in persistent oligoarticular juvenile idiopathic arthritis. AB - Juvenile idiopathic arthritis (JIA) summarizes a group of inflammatory diseases of childhood. The etiology remains still unclear. In JIA, T cells have been demonstrated to play key roles in the pathogenesis. T-cell proliferation in JIA may be different in the peripheral blood (PB) and the synovial fluid (SF). The aim of this study is to demonstrate the turnover of T cells in the PB and SF of patients with persistent oligoarticular JIA (oJIA) compared to controls. Matched pairs of samples were investigated derived from PB and SF of nine patients with persistent oJIA. The cells from PB and SF were determined by flow cytometry. The majority of the PBMC and IAMC were in phase G0/G1, with fewer than 1% in S phase. In the SF, the percentage of cells in the S phase are higher than in the PB. The percentage of cells in the S phase in SF are equal to the result in the control group. In conclusion, the turnover of synovial T cells in persistent oJIA is higher than in the PB. PMID- 20352221 TI - Serious menstrual bleeding associated with use of TNF alpha blocker: two cases. AB - Menstrual disorders associated with the use of TNF alpha blocker have been rarely reported. Herein, we reported two cases aged 31 and 41, presenting with excessive menstrual bleeding occured after adalimumab administration which was subsequently discontinued. PMID- 20352220 TI - Intracranial manifestations in SAPHO syndrome: the first case report in literature. AB - A 41-year-old woman with SAPHO syndrome presented with numbness of her left arm followed by a generalized seizure. Computed tomography and magnetic resonance imaging of the brain revealed a small ring enhancing lesion in the right parietal lobe with adjacent meningeal thickening and enhancement. Surgical removal and histopathology showed evidence of severe chronic sterile inflammation and no malignant cell. Symptoms recurred and a lesion were again detected on radiological follow-up, but improvement occurred following treatment with antibiotics and biphosphonate, achieving a low inflammatory activity, reduction in CNS lesions and relative clinical well-being. This is a first report in literature about the central nervous system involvement in a patient with SAPHO syndrome. PMID- 20352222 TI - Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus. AB - Vitamin D is a pleiotrophic hormone with immunoregulatory properties. Low levels of vitamin D have been discovered in various autoimmune diseases. Here, we investigated serum vitamin D levels in Koreans with systemic lupus erythematosus (SLE) and examined whether levels correlate with disease activity of SLE. Blood samples were prospectively collected from patients with SLE (n = 104) and normal controls (NC, n = 49) during the spring from March to May 2008. The level of serum 25-hydroxyvitamin D (25(OH)D3) was measured by radioimmunoassay. The serum 25(OH)D3 levels of patients with SLE (42.49 +/- 15.08 ng/ml) were significantly lower than NC (52.72 +/- 15.19 ng/ml, P < 0.001). Additionally, 17 patients with SLE (16.3%) had vitamin D insufficiency, while two NC had vitamin D insufficiency (4.1%). The risk of vitamin D insufficiency was 4.6-fold increased in SLE (P = 0.032). The serum 25(OH)D3 levels, adjusted with BMI, were positively correlated only with hemoglobin (beta = 0.256, P = 0.018) and serum complement 3 (beta = 0.365, P = 0.002). Serum vitamin D levels were lower, and vitamin D insufficiency was more common in Korean patients with SLE, however, our study demonstrated that vitamin D levels might not be a good marker of disease activity. PMID- 20352223 TI - Coexisting Behcet's disease and ankylosing spondylitis presented with deep venous thrombosis: a case report and review of the literature. AB - The coexistence of Behcet's disease (BD) and ankylosing spondylitis (AS) is a rare combination and described only in case reports in the literature. Although the number of reports is increasing, vascular thrombosis, which is characteristic feature of BD, was not reported in this combination until now. We present a case of a male patient with both BD and AS, presenting with deep venous thrombosis. We also reviewed the clinical features of the cases with coexistence of BD and AS. PMID- 20352224 TI - A case of Degos disease successfully treated with corticosteroid combined with cyclophosphamide. AB - Degos disease is a rare disorder characterized by systemic vasculitis involving various organs. There is no established, effective treatment for the disorder, and its prognosis is still poor. Combination therapy with corticosteroid and cyclophosphamide is considered effective for vasculitides involving the small arteries such as ANCA-associated vasculitis. We present here a 42-year-old man who developed Degos disease over several months, and was successfully treated using combined treatment with corticosteroid and cyclophosphamide. PMID- 20352225 TI - HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population. AB - The genetic components contribute to the systemic lupus erythematosus development. This study for the first time determined the distribution of the polymorphisms and linkage disequilibrium in HLA class II, MICA and PRL gene among patients suffering from SLE and healthy Czech individuals. DNA was obtained from the peripheral blood cells of 123 SLE patients and 96 healthy people. Allele variants of the HLA class II, MICA transmembrane polymorphism and PRL extrapituitary promoter -1149G/T SNP were detected using the sequence-specific primers analysis, PCR-fragment analysis and PCR-RFLP, respectively. In Czech population, only DRB1*03-DQB1*0201 haplotype is significantly associated with increased risk for SLE development: the frequency in SLE group was 44.7% in comparison with 15.2% in controls, P (c) < 0.0001; OR 4.54 CI 95% (2.36-9.09). The MICA-A5.1 allele is present significantly more often in SLE (55.7%) than controls (39.9%), P (c) = 0.005; OR 1.88 CI 95% (1.29-2.77), and the combination of HLA DRB1 *03 together with MICA-A5.1 is strongly associated with SLE [P (c) < 0.000001; OR 9.71 CI 95% (3.4-27.7)]. On the other hand, the MICA-A6 allele is less frequent in SLE patients compared to controls, 10.6% and 19.7%, respectively [P (c) = 0.035; OR 0.48 CI 95% (0.28-0.82)], and the combination of absence both alleles MICA-A6 and HLA DRB*11 seems to be risk for SLE development compared to controls, 84.6 and 70.2%, respectively, [P (c) = 0.0003 OR 2.32 CI 95% (1.47 3.70)]. We found that only G allele of the -1149 G/T SNP is associated with specific clinical manifestation of SLE, arthritis [P (c) = 0.022; OR 2.63, CI 95% (1.45-4.81)]. HLA class II-MICA combinations may increase/decrease a risk for SLE development. Multiple studies focusing on the ethnical differences as well as genetic-epigenetic relationships are necessary for better understanding SLE pathogenesis. PMID- 20352226 TI - Pneumonia in a patient with familial Mediterranean fever successfully treated with anakinra--case report and review. AB - We report the case of a 35-years-old renal transplant patient known to have familial Mediterranean fever with serum amyloid A (SAA)-amyloidosis, who presented with his second episode of bilateral pneumonia. As antimicrobials failed to control the first episode of pneumonia and all studies done were non contributory, we attributed the condition to the highly active Mediterranean fever presumably resistant to colchicine and treated the patient with the interleukin-1 receptor antagonist anakinra: the patient substantially improved by clinical symptoms, chemistry and radiological evidence within no more than 2 days and was discharged in good health after 4 days. PMID- 20352227 TI - Misdiagnosis of Behcet's disease with unknown protracted fever and chill after surgical excision of cardiac tumor. AB - Behcet's disease involving the heart is extremely rare. Sometimes it is probable to misdiagnose as infective endocarditis when protracted fever and chill occurs. We report a case of protracted pyrexia of unknown origin after surgical excision of a cardiac tumour. Clinically and pathologically a diagnosis of infective endocarditis was probable but antibiotics had no effect. After case review the diagnosis of Behcet's disease was established and the patient was treated with glucocorticoids which resulted in resolution. PMID- 20352228 TI - Bronchoalveolar lavage in systemic sclerosis with lung involvement: role and correlations with functional, radiological and scintigraphic parameters. AB - To evaluate the role and the prognostic value of bronchoalveolar lavage (BAL) in scleroderma patients with interstitial lung disease. We reviewed the records of 79 patients with systemic sclerosis (SSc) who had dyspnea and pulmonary involvement and underwent BAL study. Sixty-two patients were prospectively followed up for 12-36 months and re-evaluated by pulmonary function tests (PFTs). Seventy-nine SSc patients were enrolled (71 F and 8 M), 55 with limited and 24 with a diffuse form; mean age 55 +/- 13 years; mean disease duration 55.2 +/- 59 months. All patients were ANA positive, of these 30 were anti-topoisomerase-1 positive (anti-Topo1) and 22 were anti-centromere positive (ACA). Thirty-one patients had alveolitis (39.2%) that was neutrophilic in 12 patients, eosinophilic in 3 and mixed (neutrophilic and eosinophilic) in 16 patients. Compared to patients without alveolitis, those with alveolitis had a significant reduction of carbon monoxide diffusing capacity (DLCO), forced vital capacity (FVC) and more elevated lung high-resolution computed tomography (HRCT) scores. Furthermore, alveolar clearance was significantly accelerated. No differences were found between patients with and without alveolitis regarding disease subsets (diffuse vs limited-SSc); a significant predominance of anti-Topo1 antibodies was found in the alveolitis group and of ACA antibodies in the non-alveolitis cohort. During the follow-up, (range: 12-36 months) 62 patients, 26 with and 36 without alveolitis were re-evaluated with PFTs. In the alveolitis group, 12 patients (46.1%) showed stable lung function parameters and 14 had worsened (53.8%). In this group, 20 patients (77%) received cyclophosphamide (CYC): 11 (55%) worsened (5 of them died of cardio-pulmonary complications) and 9 (45%) remained stable. Six patients could not be treated; of these 3 remained stable and 3 worsened. Among 36 patients with normal BAL, 11 (30.5%) showed stable lung function parameters, 13 improved (36.1%) and 12 worsened (33.3%); in this last group, 2 patients died of extra-pulmonary complications. Six patients, with progression of lung fibrosis, were treated with CYC: 3 of them improved and 3 remained stable. Our study revealed a trend toward a more severe course in the SSc patients with BAL alveolitis; probably the non-significant result is related to the low number of the examined subjects and to the selection criteria. However, BAL remains the only tool to exclude lung infections and, in our experience, a useful instrument to evaluate interstitial lung disease in SSc patients. PMID- 20352229 TI - Cloning, expression and physiological analysis of broccoli catalase gene and Chinese cabbage ascorbate peroxidase gene under heat stress. AB - The objectives of this work were to clone the catalase (CAT) gene from broccoli (Brassica oleracea) and the ascorbate peroxidase (APX) gene from Chinese cabbage and measure the regulation of CAT and APX gene expressions under heat-stress conditions. Different genotypes responded differently to heat stress according to their various antioxidant enzymes and physiological parameters. CAT and APX gene expression profiles were well matched with the data for CAT and APX enzyme activities in the broccoli and Chinese cabbage plants, respectively. Full-length of the CAT and APX cDNA were 1,768 and 1,070 bp, respectively. A phylogenetic analysis of CAT and APX indicated that plant CATs and APXs diverged into two major clusters. PMID- 20352230 TI - Programmed-cell-death hallmarks in incompatible pollen and papillar stigma cells of Olea europaea L. under free pollination. AB - Programmed cell death (PCD) is a process that occurs both in animals and in plants and is an essential element in developmental processes. Pollination is a key factor in fruit production and self-incompatibility is one of the main limiting factors of this process. PCD has recently been put forward as a possible cause of pollen-growth arrest. As far as the olive is concerned, no data have been published concerning the mechanisms involved in hindering the growth of pollen tubes in incompatible pollen. Thus, we have studied olive pistils excised from freely pollinated flowers at different stages before and during the progamic phase using different cytochemical techniques, including trypan blue staining. To discover whether the elimination of incompatible pollen might be associated to PCD, we applied different tests to the excised pistils: (1) TUNEL assay; (2) DNA degradation analysis; (3) detection of caspase-3-like activity. Once we had determined that PCD was involved in pollen selection after free pollination, we conducted experiments after controlled pollination in pistils excised from flowers: (a) developing in the absence of pollen; (b) pollinated with sterile pollen that does not germinate; (c) self-pollinated; (d) pollinated with compatible pollen. Our results demonstrate that the growth of tubes in incompatible pollen is halted in the stylar area in a way that suggests the intervention of PCD. Furthermore, any pollen, even if sterile, seemed to accelerate PCD in papillar cells in the olive. PMID- 20352231 TI - Regulation of Akt during torpor in the hibernating ground squirrel, Ictidomys tridecemlineatus. AB - The 13-lined ground squirrel (Ictidomys tridecemlineatus) is capable of entering into extended periods of torpor during winter hibernation. The state of torpor represents a hypometabolic shift wherein the rate of oxygen consuming processes are strongly repressed in an effort to maintain cellular homeostasis as the availability of food energy becomes limited. We are interested in studying hibernation/torpor because of the robust state of tolerance to constrained oxygen delivery, oligemia, and hypothermia achieved by the tissues of hibernating mammals. The role of the serine/threonine kinase Akt (also known as PKB) has been examined in torpor in previous studies. However, this is the first study that examines the level of Akt phosphorylation in the liver during the two transition phases of the hibernation cycle: entrance into torpor, and the subsequent arousal from torpor. Our results indicate that Akt is activated in the squirrel liver by phosphorylation of two key residues (Thr(308) and Ser(473)) during entrance into torpor and arousal from torpor. Moreover, we observed increased phosphorylation of key substrates of Akt during the two transition stages of torpor. Finally, this study reports the novel finding that PRAS40, a component of the TORC1 multi protein complex and a potentially important modulator of metabolism, is regulated during torpor. PMID- 20352232 TI - Comparative respiratory strategies of subterranean and fossorial octodontid rodents to cope with hypoxic and hypercapnic atmospheres. AB - Subterranean rodents construct large and complex burrows and spend most of their lives underground, while fossorial species construct simpler burrows and are more active above ground. An important constraint faced by subterranean mammals is the chronic hypoxia and hypercapnia of the burrow atmosphere. The traits, regarded as "adaptations of rodents to hypoxia and hypercapnia", have been evaluated in only a few subterranean species. In addition, well-studied subterranean taxa are very divergent to their sister groups, making it difficult to assess the adaptive path leading to subterranean life. The closely related sister genera Octodon and Spalacopus of Neotropical rodents offer a unique opportunity to trace the evolution of physiological mechanisms. We studied the ventilatory responses of selected octodontid rodents to selective pressures imposed by the subterranean niche under the working hypothesis that life underground, in hypoxic and hypercapnic conditions, promotes convergent physiological changes. To perform this study we used the following species: Spalacopus cyanus (the subterranean coruros) and Octodon degus (the fossorial degus) from central Chile. Ventilatory tidal volume and respiratory frequency were measured in non-anaesthetized spontaneously breathing animals. Acute hypoxic challenges (O(2) 1-15%) and hypercapnia (CO(2) 10%) were induced to study respiratory strategies using non invasive whole body pletismography techniques. Our results show that coruros have a larger ventilatory response to acute hypoxia as than degus. On the other hand, hypercapnic respiratory responses in coruros seem to be attenuated when compared to those in degus. Our results suggest that coruros and degus have different respiratory strategies to survive in the hypoxic and hypercapnic atmospheres present in their burrows. PMID- 20352233 TI - Endoscopic third ventriculostomy in previously shunted children: a retrospective study. AB - PURPOSE: The aim of this study was to assess the mid-term results, success rates, and time-to-failure of secondary endoscopic third ventriculostomy (secondary ETV), as well as the complex management of preoperative and postoperative cares. METHODS: To this purpose, a retrospective analysis of a pediatric population of 22 children who underwent endoscopic third ventriculostomy (ETV) after shunt malfunction (secondary ETV) was performed. RESULTS: The failure rate, given by the percentage of new shunt replacement in the first 3 months after ETV, was 36%, with a mean time to failure of 14.3 days. All the failures were evident within 1 month after the ETV. Despite the small number of patients in our series, we found no significant correlation between ETV failure and both patient age and hydrocephalus etiology (p = 0.47 and p = 0.78, respectively). CONCLUSIONS: In our experience, ETV secondary to shunt malfunction in pediatric patients has a success rate of 64%. As it is a safe and rapid treatment option even in emergency conditions, it is worth performing this procedure in previously shunted children. PMID- 20352234 TI - Multidisciplinary treatment of giant invasive prolactinomas in paediatric age: long-term follow-up in two children. AB - BACKGROUND: Invasive giant prolactinomas are rare tumours, still representing a therapeutic challenge due to their characteristics of invasiveness and variable clinical course. Giant prolactinomas in childhood are extremely rare. Only single case reports have been described in the literature. CASE PRESENTATION: We report on two children who presented a progressive visual deterioration. Magnetic resonance imaging showed extensive intra-suprasellar tumour invading the anterior skull base. The laboratory investigations detected markedly elevated prolactin levels. The patients were firstly started on dopamine agonist therapy with partial reduction in size of the tumours. The debulking of the residual lesions through a transsphenoidal approach was then performed in both patients, one of whom requiring a second surgical procedure for tumour regrowth. The complete shrinkage of the residual adenomas was achieved after the treatment with conventional radiotherapy, with a follow-up of 13 and 14 years, respectively. DISCUSSION: Multidisciplinary therapeutic approach for giant prolactinomas in paediatric patients can be an effective treatment; despite the invasiveness of these tumours, the efficacy of this combined treatment can reach a satisfactory control of the disease at long term, assuring a good quality of life as well. PMID- 20352235 TI - Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. AB - Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on beta-adrenergic versus Angiotensin II (Ang II)-dependent (G(s) vs. G(alphaq) mediated) modulation of Ca(2+) (i)-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca(2+) currents and Ca(2+) (i) transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca(2+) currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca(2+)/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, beta-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca(2+)-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca(2+) (i)-dependent hypertrophic growth response to Ang II, but not to beta-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT(1) signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for beta-adrenergic Ca(2+) (i)-stimulation in adult myocytes. PMID- 20352236 TI - Balloon cells in human cortical dysplasia and tuberous sclerosis: isolation of a pathological progenitor-like cell. AB - Neural stem cells are present in the human post-natal brain and are important in the development of brain tumours. However, their contribution to non-neoplastic human disease is less clear. We have tested the hypothesis that malformations of cortical development contain abnormal (pathological) stem cells. Such malformations are a major cause of epilepsy. Two of the most common malformations [focal cortical dysplasia (FCD) and cortical tubers] are characterised by the presence of a population of abnormal cells known as balloon cells. The identity of these cells is unknown but one hypothesis is that they are an abnormal stem cell that contributes to the pathogenesis of the malformation. We have characterised in tissue, and isolated in culture, an undifferentiated population of balloon cells from surgical resections of FCD and cortical tubers. We show that beta1-integrin labels a sub-population of balloon cells with a stem cell phenotype and show for the first time that these cells can be isolated in vitro. We have characterised the immunohistochemical, morphological and ultrastructural features of these cells. This is the first isolation of an abnormal cell with features of a progenitor/stem cell from a non-neoplastic disease of the brain. PMID- 20352237 TI - Emergency peripartum hysterectomy. AB - PURPOSE: To determine the incidence, indications, risk factors and complications of peripartum hysterectomy in a tertiary teaching hospital. METHODS: The medical records of 73 patients who had undergone emergency peripartum hysterectomy between 2003 and 2008 were reviewed retrospectively. Maternal characteristics and characteristics of the present pregnancy and delivery, hysterectomy indications, operative complications, postoperative conditions and maternal outcomes were evaluated. RESULTS: There were 73 emergency peripartum hysterectomies out of 114,720 deliveries, a rate of 0.63 per 1,000 deliveries. Eleven hysterectomies were performed after vaginal delivery (0.12/1,000 vaginal deliveries) and the remaining 62 hysterectomies were performed after cesarean section (2/1,000 cesarean sections). The most common indication for hysterectomy was placenta previa and/or accreta (31 patients, 42.4%), followed by uterine atony (26 patients, 35.6%). In this study, 22 of 29 patients (75.8%) with placenta previa and 12 of 16 patients (75%) with placenta accreta had previously had cesarean sections. Cesarean section is associated with placenta previa and accreta, which are the most common causes of emergency peripartum hysterectomy. CONCLUSION: The increase in the cesarean delivery rate is leading to an increase in the rate of abnormal placentation (placenta previa and accreta), which in turn give rise to an increase in the peripartum hysterectomy rate. Cesarean section itself is also a risk factor for emergency peripartum hysterectomy. Therefore, every effort should be made to reduce the cesarean rate by performing this procedure only for valid clinical indications. The risk factors for peripartum hysterectomy should be identified antenatally. The delivery and operation should be performed in appropriate clinical settings by experienced surgeons when risk factors are identified. PMID- 20352238 TI - Should all patients referred for magnetic resonance imaging scans of their internal auditory meatus be followed up in ENT clinics? AB - Magnetic resonance imaging (MRI) is recognised as the "Gold Standard" investigation for symptoms pertaining to the inner ear and detection of retro cochlear pathology. There is still no accurate clinical predictor for cerebellopontine angle lesions and increasingly more normal scans are being performed. With constantly increasing demands on ENT outpatient clinics, our aim was to investigate whether all patients referred for MRI of their internal auditory meatus (IAM) require follow-up in ENT clinics. A retrospective study was carried out in a tertiary referral centre referring patients for MRI IAM from ENT clinics and neurotology clinics on 153 patients referred for MRI IAM performed over a 4-month period. The MRI reports and the case notes of the patients were reviewed. MRI results and patient symptoms with patient follow-up schedule and follow-up situation for at least 6 months post-scan were compared. There were two patient groups, those referred from main outpatients (81) and those referred by the audiological physicians (72). Of the total number of scans, 101 were reported as normal, 45 had incidental findings, and 7 showed pathology of the cerebellopontine angle. The presenting complaints of the patients, the scan results and the follow-up since were compared. Six months later 63% of those referred from outpatients were no longer being followed up in clinic. We suggest that 56.8% of patients referred for MRI IAM do not require ENT follow-up. Their symptoms and concerns could be dealt with at the first consultation where onward referral could be made if necessary. Once checked by the requesting clinician, uncomplicated scan results could be sent to the patients and general practitioners by post or email. This would reduce the burden on general otolaryngology outpatient clinics and improve resource utilisation. PMID- 20352239 TI - Role of narrow-band imaging and high-definition television in the surveillance of head and neck squamous cell cancer after chemo- and/or radiotherapy. AB - Narrow-band imaging (NBI) is an endoscopic technique enhancing mucosal vasculature and better identifying superficial carcinomas due to their neo angiogenic pattern. NBI accuracy is increased by combination with a high definition television (HDTV) camera. The aim of this report was to evaluate the diagnostic improvement of NBI +/- HDTV in the evaluation of head and neck squamous cell cancer (HNSCC) previously treated by chemo-radiotherapy (CHT-RT) or RT. A total of 390 patients affected by HNSCC were prospectively evaluated by NBI and white light (WL) endoscopy +/- HDTV between April 2007 and April 2009 at a single academic institution. Among them, we focused on 59 (15%) patients who received CHT-RT or RT as part of their treatment. Of 59 patients, 13 (22%) showed adjunctive preoperative NBI findings when compared to the standard WL examination. These findings were always confirmed by intraoperative HDTV NBI, while only eight (62%) were visible with HDTV WL. Of 13 lesions, 12 received histopathologic confirmation (from carcinoma in situ to invasive carcinoma). The sensitivity of flexible NBI, HDTV WL, and HDTV NBI was 100, 66 and 100%, respectively. The specificity was 98, 100, and 98%. The positive predictive value was 92, 100, and 92%. The negative predictive value was 100, 94, and 100%. The accuracy was 98, 91, and 98%. NBI +/- HDTV after CHT-RT or RT was of value in detecting tumor persistence (n = 2), early recurrences (n = 6), and metachronous tumors (n = 4). By contrast, only 1 of 59 (2%) patients was found to be false positive. PMID- 20352240 TI - Is it necessary to perform radical neck dissection as a salvage procedure for persistent or recurrent neck disease after chemoradiotherapy in patients with nasopharyngeal cancer? PMID- 20352241 TI - Exercise with visual feedback improves postural stability after vestibular schwannoma surgery. AB - We analyzed the effect of 2-week individualized visual feedback-based balance training on the postural control of patients undergoing retrosigmoid microsurgical removal of vestibular schwannoma. We performed prospective evaluation of 17 patients allocated into two groups: feedback group (9 patients, mean age 37 years) and standard physiotherapy group (8 patients, mean age 44 years). Patients in both the groups were treated once per day by intensive rehabilitation from 5th to 14th postoperative day. Rehabilitation of patients in the feedback group was performed using the visual feedback and force platform. Results were evaluated on the beginning and at the end of rehabilitation program (e.g. 5th and 14th postoperative day). Outcome measures included posturography during quiet stance under four different conditions by the modified Clinical Test for Sensory Interaction of Balance. Body sway was evaluated from center of foot pressure. Compensation of Center of pressure (CoP) parameters in stance on firm surface was similar in the control and feedback groups. However, in stance on foam surface with eyes closed the patients from the feedback group were better compensated and CoP parameters differed significantly (p < 0.05). This prospective clinical study suggests that specific exercises with visual feedback improve vestibulospinal compensation in patients after vestibular schwannoma surgery and thus can improve their quality of life. PMID- 20352242 TI - Association of tumor necrosis factor-alpha-863C/A gene polymorphism with chronic obstructive pulmonary disease. AB - The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-alpha gene promoter region at -308, -863, and 1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-alpha levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The 863 CA genotype was associated with a better FEV(1)/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m(2), p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-alpha levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-alpha -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers. PMID- 20352243 TI - Sister chromatid resolution: a cohesin releasing network and beyond. AB - When chromosomes start to assemble in mitotic prophase, duplicated chromatids are not discernible within each chromosome. As condensation proceeds, they gradually show up, culminating in two rod-shaped structures apposed along their entire length within a metaphase chromosome. This process, known as sister chromatid resolution, is thought to be a prerequisite for rapid and synchronous separation of sister chromatids in anaphase. From a mechanistic point of view, the resolution process can be dissected into three distinct steps: (1) release of cohesin from chromosome arms; (2) formation of chromatid axes mediated by condensins; and (3) untanglement of inter-sister catenation catalyzed by topoisomerase II (topo II). In this review article, we summarize recent progress in our understanding the molecular mechanisms of sister chromatid resolution with a major focus on its first step, cohesin release. An emerging idea is that this seemingly simple step is regulated by an intricate network of positive and negative factors, including cohesin-binding proteins and mitotic kinases. Interestingly, some key factors responsible for cohesin release in early mitosis also play important roles in controlling cohesin functions during interphase. Finally, we discuss how the step of cohesin release might mechanistically be coordinated with the actions of condensins and topo II. PMID- 20352244 TI - Evolution of chromosome 6 of Solanum species revealed by comparative fluorescence in situ hybridization mapping. AB - Comparative genetic linkage mapping using a common set of DNA markers in related species is an important methodology in plant genome research. Here, we demonstrate a comparative fluorescence in situ hybridization (FISH) mapping strategy in plants. A set of 13 bacterial artificial chromosome clones spanning the entire length of potato chromosome 6 was used for pachytene chromosome-based FISH mapping in seven distantly related Solanum species including potato, tomato, and eggplant. We discovered one paracentric inversion and one pericentric inversion within specific lineages of these species. The comparative FISH mapping data revealed the ancestral structure of this chromosome. We demonstrate that comparative FISH mapping is an efficient and powerful methodology to study chromosomal evolution among plant species diverged for up to 12 million years. PMID- 20352245 TI - Abnormal multifocal cerebral blood flow on Tc-99m HMPAO SPECT in a patient with anti-NMDA-receptor encephalitis. PMID- 20352246 TI - Demyelinating encephalomyeloradiculitis with Balo-like lesions. PMID- 20352247 TI - Facioscapulohumeral muscular dystrophy: a prospective study of weakness and functional impairment. AB - Only isolated prospective studies have attempted to chart the natural history of facioascapulohumeral muscular dystrophy (FSHD), a benign myopathy with notoriously variable clinical manifestations and progression. This 10-year prospective study was performed to document by simple clinical methods the natural history of 16 patients with moderately advanced FSHD. Limb strength was evaluated by the bedside manual muscle test. Global weakness was documented as a composite average muscle score (AMS). Limb function was evaluated by a non-linear grading system of important functional milestones. A scale of activities of daily living (ADL) was used to assess disability across multiple functional domains in a home environment. Six-monthly evaluations determined a linear deterioration of the mean AMS that reached statistical significance from baseline at the 5-year interval. Half of patients showed a functional decline of the arms by one grade. All patients maintained useful hand function. Three quarters of patients suffered functional decline of the legs, commonly by one grade. All patients remained ambulant. Interval analyses showed a linear deterioration of the mean ADL score that reached statistical significance from baseline at the 5-year interval. Functional deterioration was mostly due to impaired shoulder girdle activities. This study of a relatively homogeneous subgroup of FSHD patients showed a predictable rate of clinical progression in a muscle disease with a notoriously variable clinical presentation and outcome. Natural history data obtained in this study could serve as positive controls for future therapeutic trials in this patient population. The chosen clinical parameters proved useful tools for charting clinical disease progression. Functional tests proved advantageous, because decline was based partly on patient self-reports, thereby improving time and cost effectiveness. PMID- 20352248 TI - Long-lasting hemianopia due to PCA. PMID- 20352249 TI - Post-stroke pain on long-term follow-up: the Bergen stroke study. AB - The objective of this study is to evaluate characteristics and mortality related to long-term post-stroke pain (PSP). All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, between February 2006 and July 2009 received a postal questionnaire including the fatigue severity scale (FSS), the hospital anxiety and depression scale (HADSD), the Barthel index (BI), and questions regarding location of pain and pain severity at least 6 months after onset of stroke. Survival among patients returning the questionnaire was determined by November 2009. Stroke severity was defined by the modified Rankin score (mRS), 7 days after stroke onset. About 30% of the 408 patients had moderate to severe PSP. On logistic regression, PSP was associated with females (odds ratio (OR) = 2.1, p = 0.002), lower age (OR = 0.98, p = 0.04), fatigue (OR = 3.1, p < 0.001), sleep disturbances (OR = 3.3, p < 0.001), and mRS 3-5 (OR = 1.9, p = 0.03). Among patients with pareses (persistent or transient), there was no difference between paretic and non-paretic side as to frequency of limb pain on follow-up (p = 0.91). By November 2009, 26 patients had died. Cox regression analysis showed that mortality was associated with PSP (hazard ratio (HR) = 2.4, p = 0.040), high age (HR = 1.07, p = 0.001), males (HR = 2.5, p = 0.04), and low BI (HR = 0.97, p < 0.001). In conclusion, our study indicates a multifactorial basis for post-stroke pain. The main new findings were that the frequencies of pain were similar in paretic and non-paretic limbs and that long-term mortality was associated with post-stroke pain. PMID- 20352250 TI - MRI findings reveal three different types of tubers in patients with tuberous sclerosis complex. AB - Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types along a spectrum of severity, using magnetic resonance imaging (MRI) characteristics in 35 patients with TSC and history of epilepsy, and to investigate the relationship between tuber types and genetics, as well as clinical manifestations. Three types of tubers were identified based on the MRI signal intensity of their subcortical white matter component. (1) Tubers Type A are isointense on volumetric T1 images and subtly hyperintense on T2 weighted and fluid-attenuated inversion recovery (FLAIR); (2) Type B are hypointense on volumetric T1 images and homogeneously hyperintense on T2 weighted and FLAIR; (3) Type C are hypointense on volumetric T1 images, hyperintense on T2 weighted, and heterogeneous on FLAIR characterized by a hypointense central region surrounded by a hyperintense rim. Based on the dominant tuber type present, three distinct patient groups were also identified: Patients with Type A tuber dominance have a milder phenotype. Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance. PMID- 20352251 TI - Symptomatic paroxysmal dysarthria-ataxia in demyelinating diseases. AB - Paroxysmal dysarthria-ataxia syndrome (PDA) is a rare neurological disorder that can be either primary or symptomatic of acute neurological dysfunction. Episodes of symptomatic PDA are poorly documented and there are no video reports. We describe the cases of two patients with symptomatic PDA related to demyelinating diseases. Detailed studies of the patients' speech disorders showed that the dysarthria and gait disorders were of the ataxic type in both cases. Both patients had midbrain lesions at or below the level of the red nucleus, confirming that this area is critically involved in PDA. The best clinical signs for distinguishing between symptomatic and primary PDA are adult onset and short (<1 min) episodes in the former. If these signs are present, brain MRI should be used to identify a cause of symptomatic PDA. PMID- 20352252 TI - Motor cortex excitability correlates with novelty seeking in social anxiety: a transcranial magnetic stimulation investigation. AB - Social anxiety disorder (SAD) is characterised by fear of scrutiny by other people, avoidance of social situations and vegetative/motor symptomatology. The correlation between reduced striatal dopaminergic (DA) function, SAD motor symptoms and the high occurrence of SAD in patients with Parkinson's disease (PD), suggests a link between SAD and movement diseases caused by dopamine dysfunction. However, little is known about the electrophysiological aspects of SAD. We applied single- and paired-pulse transcranial magnetic stimulation (TMS) to investigate excitatory and inhibitory mechanisms of the primary motor cortex (M1) in 15 SAD patients and the relationship between these neurophysiological measures and clinical symptoms or temperamental traits. Data were compared with those obtained in 15 age- and sex-matched healthy volunteers. SAD patients showed significantly higher harm avoidance scores and lower novelty seeking scores when compared to controls. TMS measures did not significantly differ between groups. However, in SAD patients the cortical silent period (CSP) duration and the amount of long-interstimulus interval intracortical inhibition were significantly correlated with the NS score. Accordingly with NS reduction and CSP shortening reported in PD, the relationship between NS levels and the excitability of inhibitory circuits of the M1 may support the hypothesis that DA dysfunction could underlie NS deficits in SAD. Furthermore, these data suggest that "trait variables" (i.e., NS) are more closely related to neurophysiological measures than SAD symptoms, which represent "state variables" linked to social performance. PMID- 20352254 TI - Axial jerks: a clinical spectrum ranging from propriospinal to psychogenic myoclonus. AB - Propriospinal myoclonus (PSM) is a rare disorder with repetitive flexor, arrhythmic jerks of the trunk, hips and knees. Its generation is presumed to relay in the spinal cord. We report a case series of 35 consecutive patients with jerks of the trunk referred as possible PSM to a tertiary referral center for movement disorders. We review classical PSM features as well as psychogenic and tic characteristics. In our case series, secondary PSM was diagnosed in one patient only. 34 patients showed features suggestive of a psychogenic origin of axial jerks. Diagnosis of psychogenic axial jerks was based on clinical clues without additional investigations (n = 8), inconsistent findings at polymyography (n = 15), regular eye blinking preceding jerks (n = 2), or the presence of a Bereitschaftspotential (BP) (n = 9). In addition, several tic characteristics were noted. Almost all patients referred with possible PSM in our tertiary referral clinic had characteristics suggesting a psychogenic origin even in the presence of a classic polymyography pattern or in the absence of a BP. Clinical overlap with adult-onset tics seems to exist. PMID- 20352253 TI - Dissociation between time reproduction of actions and of intervals in patients with Parkinson's disease. AB - Alterations in temporal estimation have been observed in patients with Parkinson's disease (PD) and have been associated to dopaminergic dysfunction. Nevertheless, levodopa treatment and deep brain stimulation of the subthalamic nucleus (DBS-STN) have been shown to improve motor deficits and temporal estimation skills in such patients. So far, temporal estimation tasks in PD patients have evaluated the ability to reproduce intervals of time, but never the duration of an action. Here we investigated: (1) the ability of PD patients to reproduce the duration of their previous actions as compared to their ability to reproduce intervals of time and (2) the effect that DBS-STN has on both skills. Nineteen PD patients with DBS-STN and 19 controls were requested to reproduce the duration of an action and that of an interval of time. The patients were tested in the following treatment conditions: on stimulation/off medication, off stimulation/off medication and off stimulation/on medication. The results demonstrated that patients in the off stimulation/off medication condition under reproduced the duration of their actions while accurately reproducing the duration of time intervals. The accuracy of the performance improved significantly in both treatment regimens. Our results indicate that in PD patients the ability to reproduce motor acts can be dissociated from that of reproducing time intervals and that it can be improved by the administration of medical or surgical treatment. PMID- 20352255 TI - Achille Alexandre Souques (1860-1944). PMID- 20352256 TI - Analysis of long-standing nociceptive and neuropathic pain in patients with post polio syndrome. AB - The purpose of this study was to analyze pain, both nociceptive and neuropathic, in patients with post-polio syndrome (PPS) and relate the pain to age at the initial polio infection, age at examination, to gender and disability. The study was conducted in a university hospital department. Patients with PPS were interviewed at their regular visits about pain, its character, intensity and localization. A clinical examination, including a thorough neurological examination, was performed. Data included age at time of polio infection, age at time of examination and gender. Pain intensity was measured with the VAS-scale and walking capability by the WISCI-scale. One hundred sixty-three (88 women, 75 men) patients were included in the study. Pain was present in 109 (67%). Pain was more frequently reported by women (82%) than by men (49%). 96 patients experienced nociceptive pain, 10 patients both neuropathic and nociceptive pain and three experienced pure neuropathic pain. Half of the patients with pain experienced pain in more than one body region. When neuropathic pain was present, another additional neurological disorder was diagnosed. Pain was more often found in younger patients (around 70%) than in older patients (around 50%). In summary pain is common in patients with PPS and most patients experienced nociceptive pain. Women have pain more often than men. Older patients experience pain more seldom than younger patients. Age at time of primary polio infection is important for the development of pain. When neuropathic pain is present, it is important to proceed with neurological examination to find an adequate diagnosis. PMID- 20352257 TI - The validity and reliability of predicting maximal oxygen uptake from a treadmill based sub-maximal perceptually regulated exercise test. AB - The purpose of this study was to determine for the first time whether VO2max could be predicted accurately and reliably from a treadmill-based perceptually regulated exercise test (PRET) incorporating a safer and more practical upper limit of RPE 15 ("Hard") than used in previous investigations. Eighteen volunteers (21.7 +/- 2.8 years) completed three treadmill PRETs (each separated by 48 h) and one maximal graded exercise test. Participants self-regulated their exercise at RPE levels 9, 11, 13 and 15 in a continuous and incremental fashion. Oxygen uptake VO2 was recorded continuously during each 3 min bout. VO2 values for the RPE range 9-15 were extrapolated to RPE(19) and RPE(20) using regression analysis to predict individual VO2max scores. The optimal limits of agreement (LoA) between actual (48.0 +/- 6.2 ml kg(-1) min(-1)) and predicted scores were 0.6 +/- 7.1 and -2.5 +/- 9.4 ml kg(-1) min(-1) for the RPE(20) and RPE(19) models, respectively. Reliability analysis for the VO2max predictions yielded LoAs of 1.6 +/- 8.5 (RPE(20)) and 2.7 +/- 9.4 (RPE(19)) ml kg(-1) min(-1) between trials 2 and 3. These findings demonstrate that (with practice) a novel treadmill based PRET can yield predictions of VO2max that are acceptably reliable and valid amongst young, healthy, and active adults. PMID- 20352258 TI - Energy metabolism in hypoxia: reinterpreting some features of muscle physiology on molecular grounds. AB - An holistic approach for interpreting classical data on the adaptation of the animal and, particularly, of the human body to hypoxic stress was promoted by the discovery of HIF-1, the "master regulator" of cell hypoxic signaling. Mitochondrial production of ROS stabilizes the O(2)-regulated HIF-1alpha subunit of the HIF-1 dimer promoting transaction functions in a large number of potential target genes, activating transcription of sequences into RNA and, eventually, protein production. The aim of the present preliminary study is to assess whether adaptive changes in oxygen sensing and metabolic signaling, particularly in the control of energy turnover known to occur in cultured cells exposed to hypoxia, are detectable also in the muscles of animals and man. For the present analysis, data obtained from the proteome of the rat gastrocnemius and of the vastus lateralis muscle of humans together with functional measurements were compared with homologous data from hypoxic cultured cells. In particular, the following variables were assessed: (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure. Despite the limited number of observations and the differences in the experimental approach, some initial interesting results were obtained encouraging to pursue this innovative effort. PMID- 20352259 TI - Gallbladder bed irrigation with bupivacaine improves pulmonary functions after laparoscopic cholecystectomy. AB - PURPOSE: Afferent stimulus arising from gallbladder and its bed may elicit reflex inhibition of the diaphragm. Pulmonary function would be improved by blocking this stimulus after laparoscopic cholecystectomy. This randomized prospective study evaluated this hypothesis in patients who underwent laparoscopic cholecystectomy. MATERIALS AND METHODS: During the study period, 30 patients who underwent laparoscopic cholecystectomy were randomly divided into three groups. Group I: Laparoscopic cholecystectomy; Group II: Laparoscopic cholecystectomy + irrigation of gallbladder bed with 20 mL 0.5% bupivacaine solution; Group III: Laparoscopic cholecystectomy + irrigation of gallbladder bed with bupivacaine + 10 mL 0.5% bupivacaine solution was given via a catheter every 6 h. Pulmonary function tests were performed on the day before the operation and in the morning of the first postoperative day. Forced vital capacity (FVC), forced expiratory volume at 1 s (FEV-1), and forced expiratory flow at 25% to 75% (FEF 25-75%) were obtained. RESULTS: Postoperative FVC measured 53.3 +/- 4.5% of preoperative function for group I, 70.8 +/- 5.7% for group II, and 68.8 +/- 4.7% for group III (p < 0.05). Postoperative FEV-1 measured 52.8 +/- 5.3% of preoperative function for group I, 69.7 +/- 4.9% for group II, and 70.5 +/- 5% for group III (p < 0.05). Postoperative FEF 25-75% measured 61.1 +/- 4.6% of the preoperative function for group I, 73.6 +/- 3% for group II, and 72.1 +/- 6% for group III (p < 0.05). CONCLUSION: The results from this study indicated that considerable improvement of pulmonary function was acquired by gallbladder bed irrigation with bupivacaine after laparoscopic cholecystectomy. PMID- 20352260 TI - Youngest patient of the world with largest lipoma on the floor of the mouth: report from Bangladesh. PMID- 20352261 TI - Prospective randomised study to evaluate the use of DERMABOND ProPen (2 octylcyanoacrylate) in the closure of abdominal wounds versus closure with skin staples in patients undergoing elective colectomy. AB - BACKGROUND: Topical 2-octylcyanoacrylate tissue (OCA) adhesive has been used as an alternative to close wounds with a comparable cosmetic outcome. The use of 2 OCA in the closure of abdominal laparotomy wounds has not been thoroughly evaluated. Our aim was to compare 2-OCA with conventional skin stapling devices in colorectal surgery. METHODS: A prospective randomised study was conducted in which 74 consecutive patients above the age of 21 undergoing open elective colectomies for benign or malignant indications were allocated to skin closure with 2-OCA or skin staples. Cosmetic outcome as assessed with the Hollander Cosmesis Scale with a single assessor, complication rates, and patient satisfaction were recorded at discharge (4-10POD) 2 weeks after discharge and then at 3 months. RESULTS: Of the 74 patients, 38 were randomised to skin staples and 36 to 2-OCA. There was no significant difference in cosmetic outcomes between the two groups as assessed with a visual analogue scale or the Hollander Cosmesis Scale but showed a trend to better cosmetic outcomes in the 2-OCA group. Patient satisfaction scores were higher but did not reach statistical significance. The time taken to close a wound with 2-OCA was significantly longer than with skin staples. There was no statistical difference in rates of wound infection. CONCLUSION: 2-OCA is a safe and effective means of skin closure in patients undergoing elective colectomies with a good and at least equivalent outcome to traditional methods of closure. PMID- 20352262 TI - Sugarcane DIRIGENT and O-methyltransferase promoters confer stem-regulated gene expression in diverse monocots. AB - Transcription profiling analysis identified Saccharum hybrid DIRIGENT (SHDIR16) and Omicron-Methyltransferase (SHOMT), putative defense and fiber biosynthesis related genes that are highly expressed in the stem of sugarcane, a major sucrose accumulator and biomass producer. Promoters (Pro) of these genes were isolated and fused to the beta-glucuronidase (GUS) reporter gene. Transient and stable transgene expression analyses showed that both Pro( DIR16 ):GUS and Pro( OMT ):GUS retain the expression characteristics of their respective endogenous genes in sugarcane and function in orthologous monocot species, including rice, maize and sorghum. Furthermore, both promoters conferred stem-regulated expression, which was further enhanced in the stem and induced in the leaf and root by salicylic acid, jasmonic acid and methyl jasmonate, key regulators of biotic and abiotic stresses. Pro( DIR16 ) and Pro( OMT ) will enable functional gene analysis in monocots, and will facilitate engineering monocots for improved carbon metabolism, enhanced stress tolerance and bioenergy production. PMID- 20352263 TI - Identification of genes that affect sensitivity to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae. AB - Small molecules that exhibit biological effects have been successfully used to study various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analog that affects various biological processes, such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to modulate these phenomena by changing chromatin structure and gene expression, the molecular mechanisms for the action of BrdU are not understood well. To analyze the molecular mechanisms of BrdU with genetic methods, we used the yeast Saccharomyces cerevisiae as a model. Our genetic screening has revealed that a defect in MPT5/HTR1/UTH4/PUF5 led to an increased sensitivity to BrdU, and that overexpression of VHT1 or SDT1 led to resistance to BrdU. The increased sensitivity to BrdU caused by a defect in MPT5 was suppressed by a mutation in SIR2, SIR3, or SIR4, which is involved in chromatin silencing and transcriptional repression. These findings suggest that chromatin silencing proteins are involved in the modulation of the cellular phenomena by BrdU, and would provide clues to answer the old question of how BrdU affects various biological phenomena. PMID- 20352264 TI - Two-stage case-control designs for rare genetic variants. AB - The search for the association of rare genetic variants with common diseases is of high interest, yet challenging because of cost considerations. We present an efficient two-stage design that uses diseased cases to first screen for rare variants at stage-1. If too few cases are found to carry any variants, the study stops. Otherwise, the selected variants are screened at stage-2 in a larger set of cases and controls, and the frequency of variants is compared between cases and controls by an exact test that corrects for the stage-1 ascertainment. Simulations show that our new method provides conservative Type-I error rates, similar to the conservative aspect of Fisher's exact test. We show that the probability of stopping at stage-1 increases with a smaller number of cases screened at stage-1, a larger stage-1 continuation threshold, or a smaller carrier probability. Our simulations also show how these factors impact the power at stage-2. To balance stopping early when there are few variant carriers versus continuation to stage-2 when the variants have a reasonable effect size on the phenotype, we provide guidance on designing an optimal study that minimizes the expected sample size when the null hypothesis is true, yet achieves the desired power. PMID- 20352265 TI - Native species behaviour mitigates the impact of habitat-forming invasive seaweed. AB - Habitat-forming invasive species cause large, novel changes to the abiotic environment. These changes may elicit important behavioural responses in native fauna, yet little is known about mechanisms driving this behaviour and how such trait-mediated responses influence the fitness of native species. Low dissolved oxygen is a key abiotic change created by the habitat-forming invasive seaweed, Caulerpa taxifolia, which influences an important behavioural response (burrowing depth) in the native infaunal bivalve Anadara trapezia. In Caulerpa-colonised areas, Anadara often emerged completely from the sediment, and we experimentally demonstrate that water column hypoxia beneath the Caulerpa canopy is the mechanism instigating this "pop-up" behaviour. Importantly, pop-up in Caulerpa allowed similar survivorship to that in unvegetated sediment; however, when we prevented Anadara from popping-up, they suffered >50% mortality in just 1 month. Our findings not only highlight the substantial environmental alteration by Caulerpa, but also an important role for the behaviour of native species in mitigating the effects of habitat-forming invasive species. PMID- 20352267 TI - Characterization of novel porcine sapoviruses. AB - Sapoviruses are common caliciviruses known to cause enteric diseases in humans and animals. SaVs are genetically highly heterogeneous and are presently classified in five genogroups that are further subdivided in a number of genotypes. In recent years, a number of novel animal SaV strains, mostly of swine origin, have been partially characterized and proposed to represent novel genogroups or genotypes. We previously reported the detection and partial characterization of a wide range of variable and novel SaV strains of uncertain taxonomic status in Canadian swine. We now report on further genomic characterization of two novel strains to clarify their taxonomic relationship to other swine and human SaVs. Detailed analysis of different regions of their genomes, including determination of their complete capsid sequence, did not permit clear taxonomic assignment according to current criteria. This situation appears reminiscent of that of a number of SaV strains of swine origin and calls for a classification update for this calicivirus genus. We also report the detection of swine GIII SaVs for the first time in Canada. PMID- 20352266 TI - Physical activity, quality of life, and the interest in physical exercise programs in patients undergoing palliative chemotherapy. AB - PURPOSE: Quality of life is of major importance in patients with advanced cancers undergoing palliative chemotherapy. In contrast to the number of studies on physical activity in patients with curable malignancies, data on patients undergoing palliative chemotherapy are scarce. METHODS: A total of 53 patients receiving palliative chemotherapy on an outpatient basis were interviewed using three standardized questionnaires within a time period of 4 weeks (Questionnaire for Measurement of Habitual Physical Activity, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C13 questionnaire, International Physical Activity questionnaire), and a questionnaire regarding patients' acceptance of a potential physical training program. RESULTS: Thirty six percent of the patients still performed self-instructed physical activities during palliative chemotherapy. Patients showed significantly higher values in the "leisure time index" during their malignancy than before (p < 0.01). Significantly positive correlations were found between "work index" and quality of life (p = 0.004), "work index" and physical function (p = 0.02), and "hours of physical activity per week" and quality of life (p < 0.05). A negative correlation was found between "work index" and fatigue (p < 0.05). Quality of life scores were significantly higher in patients with sportive activities >= 9 metabolic equivalent (MET) h/week than in patients with <9 MET h/weeks (p < 0.01). Sixty percent of patients indicated that they would be willing to participate in an individually adapted activity training program. CONCLUSIONS: In patients undergoing palliative chemotherapy, a statistically significant positive correlation between physical activity and quality of life could be demonstrated. About two thirds of critically ill patients are interested in participating in training programs. PMID- 20352268 TI - A leucine-rich repeat assembly approach for homology modeling of the human TLR5 10 and mouse TLR11-13 ectodomains. AB - So far, 13 groups of mammalian Toll-like receptors (TLRs) have been identified. Most TLRs have been shown to recognize pathogen-associated molecular patterns from a wide range of invading agents and initiate both innate and adaptive immune responses. The TLR ectodomains are composed of varying numbers and types of leucine-rich repeats (LRRs). As the crystal structures are currently missing for most TLR ligand-binding ectodomains, homology modeling enables first predictions of their three-dimensional structures on the basis of the determined crystal structures of TLR ectodomains. However, the quality of the predicted models that are generated from full-length templates can be limited due to low sequence identity between the target and templates. To obtain better templates for modeling, we have developed an LRR template assembly approach. Individual LRR templates that are locally optimal for the target sequence are assembled into multiple templates. This method was validated through the comparison of a predicted model with the crystal structure of mouse TLR3. With this method, we also constructed ectodomain models of human TLR5, TLR6, TLR7, TLR8, TLR9, and TLR10 and mouse TLR11, TLR12, and TLR13 that can be used as first passes for a computational simulation of ligand docking or to design mutation experiments. This template assembly approach can be extended to other repetitive proteins. PMID- 20352269 TI - Blue rubber bleb nevus syndrome with late onset of central nervous system symptomatic involvement. AB - Blue rubber bleb nevus syndrome is a rare vascular disorder characterized by cavernous angiomas of skin and other organs including the gastrointestinal tract. The central nervous system involvement is seldom reported, and neurological symptoms at onset in adulthood are extremely rare. Here, we describe a case of 82 year-old patient presenting multiple skin haemangiomas for some years, who was admitted for a brain hemorrhage. The MRI demonstrated the presence of multiple cavernous angiomas within the cerebral tissue. PMID- 20352270 TI - Transcriptome profiling of embryonic development rate in rainbow trout advanced backcross introgression lines. AB - In rainbow trout (Oncorhynchus mykiss) and other fishes, embryonic development rate is an ecologically and evolutionarily important trait that is closely associated with survival and physiological performance later in life. To identify genes differentially regulated in fast and slow-developing embryos of rainbow trout, we examined gene expression across developmental time points in rainbow trout embryos possessing alleles linked to a major quantitative trait loci (QTL) for fast versus slow embryonic development rate. Whole genome expression microarray analyses were conducted using embryos from a fourth generation backcross family, whereby each backcross generation involved the introgression of the fast-developing alleles for a major development rate QTL into a slow developing clonal line of rainbow trout. Embryos were collected at 15, 19, and 28 days post-fertilization; sex and QTL genotype were determined using molecular markers, and cDNA from 48 embryos were used for microarray analysis. A total of 183 features were identified with significant differences between embryonic development rate genotypes. Genes associated with cell cycle growth, muscle contraction and protein synthesis were expressed significantly higher in embryos with the fast-developing allele (Clearwater) than those with the slow-developing allele (Oregon State University), which may associate with fast growth and early body mass construction in embryo development. Across time points, individuals with the fast-developing QTL allele appeared to have earlier onset of these developmental processes when compared to individuals with the slow development alleles, even as early as 15 days post-fertilization. Differentially expressed candidate genes chosen for linkage mapping were localized primarily to regions outside of the major embryonic development rate QTL, with the exception of a single gene (very low-density lipoprotein receptor precursor). PMID- 20352272 TI - Mapping QTL for an adaptive trait: the length of caudal fin in Lates calcarifer. AB - The caudal fin represents a fundamental design feature of fishes and plays an important role in locomotor dynamics in fishes. The shape of caudal is an important parameter in traditional systematics. However, little is known about genes involved in the development of different forms of caudal fins. This study was conducted to identify and map quantitative trait loci (QTL) affecting the length of caudal fin and the ratio between tail length and standard body length in Asian seabass (Lates calcarifer). One F1 family containing 380 offspring was generated by crossing two unrelated individuals. One hundred and seventeen microsatellites almost evenly distributed along the whole genome were genotyped. Length of caudal fin at 90 days post-hatch was measured. QTL analysis detected six significant (genome-wide significant) and two suggestive (linkage-group-wide significant) QTL on seven linkage groups. The six significant QTL explained 5.5 16.6% of the phenotypic variance, suggesting these traits were controlled by multiple genes. Comparative genomics analysis identified several potential candidate genes for the length of caudal fin. The QTL for the length of caudal fin detected for the first time in marine fish may provide a starting point for the future identification of genes involved in the development of different forms of caudal fins in fishes. PMID- 20352274 TI - A promising evaluation method for dead leaves of Posidonia oceanica (L.) in the adsorption of methyl violet. AB - Posidonia oceanica (Linnaeus) Delile is an endemic species in the Mediterranean Sea. In the present study, dead leaves of P. oceanica (L.) which are accumulated on the beach seasonally were used as an alternative low cost biosorbent to remove methyl violet (MV) from aqueous solution. In order to explain the adsorption kinetics, pseudo first-order and pseudo second-order kinetic models were investigated. It was obtained that the pseudo second-order model was well in line with our experimental results. Equilibrium data were analyzed according to Langmuir, Freundlich, and Dubinin-Radushkevich equations. Langmuir isotherm model corresponded well with equilibrium data than the others, and the maximum adsorption capacity of the biomass was found to be 119.05 mg g-1 at 45 degrees C. Thermodynamic parameters, DeltaG degrees , DeltaH degrees , and DeltaS degrees , were calculated according to van't Hoff equation. Negative values of Gibbs free energy imply that the process is spontaneous. Consequently, dried biomass of this species can be an alternative and low cost material for the removal of MV from wastewaters. Moreover, since the remarkable adsorption capacity of these dead leaves compared to other low cost adsorbents has been observed, this beach waste could provide an economic contribution to the countries in the Mediterranean region. PMID- 20352271 TI - Immunological control of fish diseases. AB - All metazoans possess innate immune defence system whereas parameters of the adaptive immune system make their first appearance in the gnathostomata, the jawed vertebrates. Fish are therefore the first animal phyla to possess both an innate and adaptive immune system making them very interesting as regards developmental studies of the immune system. The massive increase in aquaculture in recent decades has also put greater emphasis on studies of the fish immune system and defence against diseases commonly associated with intensive fish rearing. Some of the main components of the innate and adaptive immune system of fish are described. The innate parameters are at the forefront of immune defence in fish and are a crucial factor in disease resistance. The adaptive response of fish is commonly delayed but is essential for lasting immunity and a key factor in successful vaccination. Some of the inherent and external factors that can manipulate the immune system of fish are discussed, the main fish diseases are listed and the pathogenicity and host defence discussed. The main prophylactic measures are covered, including vaccination, probiotics and immunostimulation. A key element in the immunological control of fish diseases is the great variation in disease susceptibility and immune defence of different fish species, a reflection of the extended time the present day teleosts have been separated in evolution. Future research will probably make use of molecular and proteomic tools both to study important elements in immune defence and prophylactic measures and to assist with breeding programmes for disease resistance. PMID- 20352273 TI - Molecular cloning of cecropin B responsive endonucleases in Yersinia ruckeri. AB - We have previously demonstrated that Yersinia ruckeri resists cecropin B in an inducible manner. In this study, we sought to identify the molecular changes responsible for the inducible cecropin B resistance of Y. ruckeri. Differences in gene expression associated with the inducible resistance were investigated. Cultures of Y. ruckeri were exposed to a sublethal concentration of cecropin B and resultant changes in the messenger RNA population of the bacteria were assayed using the differential display reverse transcription polymerase chain reaction (DD-RT-PCR). A single band was consistently increased in intensity in all repeats of the experiment. The band was excised, cloned, sequenced, and used to screen a Y. ruckeri genomic DNA library. The DD-RT-PCR fragment shared 100% identity to the cDNA sequence of an ATP-dependent endonuclease of the overcome lysogenization defect (OLD) family of Y. ruckeri 29473. The genomic clone that was recovered was not identical to the DD-RT-PCR clone, but harbored a gene for a secreted endonuclease 1 (nucM) homologue. It was determined that transcription of the gene was upregulated following exposure to cecropin B via RT-PCR. Furthermore, an increase in the nuclease activity of culture supernatants of Y. ruckeri following exposure to cecropin B was demonstrated. These findings demonstrate that cecropin B exposure increases the expression of at least two endonucleases in Y. ruckeri. The production and secretion of an endonuclease by Y. ruckeri in response to an antimicrobial peptide indicates the involvement of both intracellular and extracellular DNA in the toxic effects of cecropin B. PMID- 20352275 TI - Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience. AB - BACKGROUND: Desmoids are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP), 70% being intra-abdominal desmoids (IAD). Since the morbidity and mortality due to desmoids is almost entirely attributable to IAD, we aimed to identify specifically risk factors predicting IAD development in FAP. METHODS: We undertook a retrospective review of our institutional database. Multivariate analysis was performed, and hazard ratios (HR) calculated for variables including female gender, 3' APC mutation, surgical intervention for FAP (colectomy with ileo-rectal anastomosis or restorative proctocolectomy), age at surgery and family history (FH) of desmoids. RESULTS: Of the 558 patients analysed, 49 (9%) developed IAD; 22 (4%) diagnosed intra-operatively and 27 (5%) developing over a median post-operative period of 34 (7-120) months. 75% of IAD had developed before age 40. A 3' APC mutation (HR 5.2, 95% CI 2.1-13.3, P = 0.001), positive FH (HR 2.5, 95% CI 1.4-4.6, P = 0.003) and female gender (HR 1.9, 95% CI 1.0-3.5, P = 0.04) were found to be predictive of IAD development. No significant difference in IAD risk was detected between the type of surgical intervention (P = 0.37) or age at surgery (P = 0.29). CONCLUSIONS: Our analysis confirms 3' APC mutation to be the most significant risk factor for IAD development. The independent association between positive FH and IAD risk suggests the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors can be meaningfully modified. Delaying prophylactic surgery may be appropriate in female patients with a 3' APC mutation and attenuated polyposis. PMID- 20352276 TI - Endoluminal vacuum therapy for anastomotic leaks after rectal surgery. AB - Anastomotic leakage after rectal surgery is a very serious complication and is the main cause of postoperative morbidity and mortality. We describe three cases of rectal leakage which we treated with endoscopic vacuum-assisted closure. We used the Endo-SPONGE (B. Braun Aesculap AG, Germany), which consists of an open cell, cylindrical polyurethane sponge connected to a drainage tube which is linked to a vacuum system to exert constant suction. The possible role of this new tool in the management of anastomotic leaks is also discussed. PMID- 20352277 TI - Genotyping of Pseudomonas aeruginosa isolated from cockroaches and human urine. AB - Molecular-epidemiological analysis of Pseudomonas aeruginosa isolated from cockroaches captured in hospitals and from patient urine was performed, employing randomly amplified polymorphic DNA (RAPD) analysis to investigate the usefulness of RAPD analysis. Four specific bands at positions of 993, 875, 521, and 402 bp were commonly detected using primer 272 in 16 of 45 cockroach-derived strains (35.6%), but not in 21 urine-derived strains. On analysis using primer 208, 4 specific bands at positions of 1,235, 1,138, 1,068, and 303 bp were commonly detected in 15 of the 45 cockroach-derived (33.3%) and 10 of the 21 patient urine derived (47.6%) strains, in a total of 25 of 66 strains (37.8%). On cluster analysis, 12 (48.5%) and 16 (66.7%) clusters were grouped based on a homology of 89% or greater, using primer 272 and primer 208, respectively, showing that primer 208 was suitable for the confirmation of diversity. Seven patterns were clustered based on 100% homology using either primer, and 6 of these consisted of only cockroach-derived strains. In the individual groups with 100% homology, all strains in the group were isolated at an identical site during the same period. P. aeruginosa isolated from cockroaches showed diverse genotypes suggesting several sources of contamination, indicating the necessity for investigating infection control targeting cockroaches inhabiting hospitals. PMID- 20352278 TI - Investigation of pneumonia-causing pathogenic organisms in children and the usefulness of tebipenem pivoxil for their treatment. AB - We investigated the usefulness of the novel oral carbapenem antibiotic tebipenem pivoxil (TBPM-PI) for treating bacterial pneumonia in children. Sputum and nasopharyngeal swabs were collected simultaneously, and causative organisms were identified by conventional bacterial culture together with exhaustive bacterial and viral identification by real-time polymerase chain reaction (PCR). The subjects were eight patients diagnosed with mild or moderate pneumonia at Sotobo Children's Clinic Outpatient Department between October 2006 and June 2007. TBPM PI was administered at the recommended clinical dose of 4 mg/kg b.i.d. to five patients and at a high dose of 6 mg/kg b.i.d. to three patients. Sputum was collected from all patients, and 11 strains were detected from washed sputum culture. Causative organisms were mainly Streptococcus pneumoniae (3 strains) and Haemophilus influenzae (6 strains), and nasopharyngeal swabs showed the same organisms as coughed-up sputum. Real-time PCR for individual viruses and Mycoplasma pneumoniae identified four cases of only bacterial infection, one case of M. pneumoniae coinfection, two cases of viral coinfection, and one case of both viral and M. pneumoniae coinfection. The clinical results indicated efficacy in all patients, and causative organisms were 100% eliminated. In the four patients with only bacterial infection, the average fever of 38.9 degrees C at the start of treatment normalized the following day, showing excellent efficacy. No clinically problematic adverse events occurred, and compliance was good. We consider that these cases provide valuable insights into the identity of pathogenic organisms of pneumonia in children and the possible role of TBPM-PI in outpatient treatment. PMID- 20352279 TI - Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype. AB - Most in vivo studies addressing the skeletal responses of mice to mechanical loading have targeted cortical bone. To investigate trabecular bone responses also we have developed a caudal vertebral axial compression device (CVAD) that transmits mechanical loads to compress the fifth caudal vertebra via stainless steel pins inserted into the forth and sixth caudal vertebral bodies. Here, we used the CVAD in C57BL/6 (B6) and C3H/Hej (C3H) female mice (15 weeks of age) to investigate whether the effect of regular bouts of mechanical stimulation on bone modeling and bone mass was dependent on dose and genotype. A combined micro computed tomographic and dynamic histomorphometric analysis was carried out at the end of a 4-week loading regimen (3,000 cycles, 10 Hz, 3 x week) for load amplitudes of 0N, 2N, 4N and 8N. Significant increases in trabecular bone mass of 9 and 21% for loads of 4N and 8N, respectively, were observed in B6 mice. A significant increase of 10% in trabecular bone mass occurred for a load of 8N in the C3H strain. For other loads, no significant increases were detected. Both mouse strains exhibited substantial increases in trabecular bone formation rates for all loads, B6: 111% (2N), 86% (4N), 164% (8N), C3H: 41% (2N), 38% (4N), 141% (8N). Significant decreases in osteoclast number of 146 and 93% for a load of 8N were detected in B6 and C3H mice, respectively. These findings demonstrate that the effect of loading on the structural and functional parameters of bone is dose and genotype dependent. The caudal vertebral loading model established here is proposed for further studies addressing the molecular processes involved in the skeletal responses to mechanical stimuli. PMID- 20352281 TI - Evaluation of objective similarity measures for selecting similar images of mammographic lesions. AB - The purpose of this study was to investigate four objective similarity measures as an image retrieval tool for selecting lesions similar to unknown lesions on mammograms. Measures A and B were based on the Euclidean distance in feature space and the psychophysical similarity measure, respectively. Measure C was the sequential combination of B and A, whereas measure D was the sequential combination of A and B. In this study, we selected 100 lesions each for masses and clustered microcalcifications randomly from our database, and we selected five pairs of lesions from 4,950 pairs based on all combinations of the 100 lesions by use of each measure. In two observer studies for 20 mass pairs and 20 calcification pairs, six radiologists compared all combinations of 20 pairs by using a two-alternative forced-choice method to determine the subjective similarity ranking score which was obtained from the frequency with which a pair was considered as more similar than the other 19 pairs. In both mass and calcification pairs, pairs selected by use of measure D had the highest mean value of the average subjective similarity ranking scores. The difference between measures D and A (P = 0.008 and 0.024), as well as that between measures D and B (P = 0.018 and 0.028) were statistically significant for masses and microcalcifications, respectively. The sequential combination of the objective similarity measure based on the Euclidean distance and the psychophysical similarity measure would be useful in the selection of images similar to those of unknown lesions. PMID- 20352280 TI - Freehand liver volumetry by using an electromagnetic pen tablet: accuracy, precision, and rapidity. AB - The purpose of this study is to assess the accuracy, precision, and rapidity of liver volumes calculated by using a freehand electromagnetic pen tablet contourtracing method as compared with the volumes calculated by using the standard optical mouse contourtracing method. The imaging data used as input for accuracy and precision testing were computed by software developed in our institution. This computer software can generate models of solid organs and allows both standard mouse-based and electromagnetic pen-driven segmentation (number of data sets, n = 70). The images used as input for rapidity testing was partly computed by modeling software (n = 70) and partly selected from contrast enhanced computed tomography (CT) examinations (n = 12). Mean volumes and time required to perform the segmentation, along with standard deviation and range values with both techniques, were calculated. Student's t test was used to assess significance regarding mean volumes and time calculated by using both segmentation techniques on phantom and CT data sets. P value was also calculated. The mean volume difference was significantly lower with the use of the freehand electromagnetic pen as compared with the optical mouse (0.2% vs. 1.8%; P < .001). The mean segmentation time per patient was significantly shorter with the use of the freehand electromagnetic pen contourtracing method (354.5 vs. 499.1 s on phantoms; 457.4 vs. 610.0 s on CT images; P < .001). Freehand electromagnetic pen based volumetric technique represents a technologic advancement over manual mouse based contourtracing because of the superior statistical accuracy and sensibly shorter time required. Further studies focused on intra- and interobserver variability of the technique need to be performed before its introduction in clinical application. PMID- 20352282 TI - Typical accuracy and quality control of a process for creating CT-based virtual bone models. AB - A pragmatic method for assessing the accuracy and precision of a given processing pipeline required for converting computed tomography (CT) image data of bones into representative three dimensional (3D) models of bone shapes is proposed. The method is based on coprocessing a control object with known geometry which enables the assessment of the quality of resulting 3D models. At three stages of the conversion process, distance measurements were obtained and statistically evaluated. For this study, 31 CT datasets were processed. The final 3D model of the control object contained an average deviation from reference values of -1.07 +/- 0.52 mm standard deviation (SD) for edge distances and -0.647 +/- 0.43 mm SD for parallel side distances of the control object. Coprocessing a reference object enables the assessment of the accuracy and precision of a given processing pipeline for creating CT-based 3D bone models and is suitable for detecting most systematic or human errors when processing a CT-scan. Typical errors have about the same size as the scan resolution. PMID- 20352283 TI - Infective endocarditis complicated by intracerebral hemorrhage due to Lactococcus lactis subsp. cremoris. PMID- 20352284 TI - Prosthetic valve/conduit infection caused by Cardiobacterium valvarum. PMID- 20352285 TI - WHO First Global Patient Safety Challenge: saving lives in healthcare through clean hands. PMID- 20352286 TI - Pulmonary toxoplasmosis, a rare but severe manifestation of a common opportunistic infection in late HIV presenters: report of two cases. AB - Pulmonary toxoplasmosis is rare, particularly in the era of highly active antiretroviral therapy (HAART). Here, we describe two severe cases in patients not known to be HIV-infected. In both patients, early diagnosis and therapy led to a favourable outcome. Pulmonary toxoplasmosis should be considered in the differential diagnosis in potentially HIV-infected patients with respiratory symptoms. PMID- 20352287 TI - Safety and efficacy of a saquinavir-containing antiretroviral regimen in previously ART-naive or pretreated but protease inhibitor-naive HIV-positive patients. AB - BACKGROUND: The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500-mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of antiretroviral therapy (ART)-naive and pretreated but protease inhibitor (PI)-naive patients. METHODS: This was a multicenter, prospective, open-label, 48-week observational cohort study. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48. Efficacy assessments included changes in the proportion of patients with HIV-1 RNA <50 and <400 copies/ml, and changes in CD4 cell count from baseline to week 48. RESULTS: The analysis included 275 ART-naive and 179 pretreated but PI-naive patients. The proportion of ART-naive patients achieving <50 copies/ml by 48 weeks was 53.1% by intent-to-treat (ITT) analysis and 67.3% using last observation carried forward (LOCF) analysis. In pretreated but PI naive patients, the proportions achieving <50 copies/ml by 48 weeks were 53.1% (ITT) and 70.4% (LOCF). The median increase in CD4 count at week 48 was +174 cells/mm3 (interquartile range [IQR] 86, 265) in the ART-naive group and +100 cells/mm3 (IQR 0, 209) in the pretreated but PI-naive group (p < 0.01 for both; LOCF). Drug-related adverse events were reported in 7.6% of ART-naive and 2.8% of pretreated but PI-naive patients. Treatment with SQV/r was stopped in 21.5% of ART-naive and 17.9% of pretreated but PI-naive patients (due to side effects in 3.3% and 2.8%, respectively). There were no clinically relevant changes in liver enzyme levels. Overall, the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels increased to week 48, although the levels remained within normal ranges in the majority of patients. CONCLUSIONS: The results of this observational cohort study of treatment with the 500-mg tablet formulation of SQV are consistent with high efficacy and tolerability results seen in controlled studies of SQV/r. This analysis confirms that SQV/r is effective and well tolerated in ART-naive and pretreated but PI naive patients in 'real-world' clinical settings. PMID- 20352288 TI - Overexpression of ribosome recycling factor causes increased production of avermectin in Streptomyces avermitilis strains. AB - Ribosome recycling factor (RRF), encoded by frr gene, is involved in the release of ribosomes from the translational post-termination complex for a new round of initiation. In this study, the frr gene with either its own promoter or with ermE p was cloned into a multi-copy vector, pKC1139, and a single-site integrative vector, pSET152, respectively. The resulting plasmids were transformed into Streptomyces avermitilis wild-type strain ATCC31267, avermectin high-producing mutant strain 76-02-e, and the engineered strain GB-165 that produces only avermectin B. The results showed that overexpression of frr increased avermectin yield (by 3- to 3.7-fold in the wild-type strain) and revealed an frr gene "copy number effect"; i.e., multiple copies of frr had a greater promoting effect on avermectin production than a single copy in each of the three transformed S. avermitilis strains. Comparison of the growth and expression of the ave genes in an frr-overexpressing strain and wild-type ATCC31267 indicated that frr overexpression promoted cell growth as well as the expression of ave genes (including pathway-specific positive regulatory gene aveR for avermectin biosynthesis and ave structural genes), leading in turn to avermectin overproduction. These findings provide an effective approach for the improvement of antibiotic production in Streptomyces. PMID- 20352289 TI - Fast reduction of undersampling artifacts in radial MR angiography with 3D total variation on graphics hardware. AB - OBJECTIVE: Subsampling of radially encoded MRI acquisitions in combination with sparsity promoting methods opened a door to significantly increased imaging speed, which is crucial for many important clinical applications. In particular, it has been shown recently that total variation (TV) regularization efficiently reduces undersampling artifacts. The drawback of the method is the long reconstruction time which makes it impossible to use in daily clinical practice, especially if the TV optimization problem has to be solved repeatedly to select a proper regularization parameter. MATERIALS AND METHODS: The goal of this work was to show that for the case of MR Angiography, TV filtering can be performed as a post-processing step, in contrast to the common approach of integrating TV penalties in the image reconstruction process. With this approach, it is possible to use TV algorithms with data fidelity terms in image space, which can be implemented very efficiently on graphic processing units (GPUs). The combination of a special radial sampling trajectory and a full 3D formulation of the TV minimization problem is crucial for the effectiveness of the artifact elimination process. RESULTS AND CONCLUSION: The computation times of GPU-TV show that interactive elimination of undersampling artifacts is possible even for large volume data sets, in particular allowing the interactive determination of the regularization parameter. Results from phantom measurements and in vivo angiography data sets show that 3D TV, together with the proposed sampling trajectory, leads to pronounced improvements in image quality. However, while artifact removal was very efficient for angiography data sets in this work, it cannot be expected that the proposed method of TV post-processing will work for arbitrary types of scans. PMID- 20352290 TI - The nuclear transport capacity of a human-pancreatic ribonuclease variant is critical for its cytotoxicity. AB - We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it with cytotoxic activity because although the variant poorly evades the ribonuclease inhibitor in vitro, it is routed to the nucleus, which is devoid of the inhibitor. In this work, we have investigated the relationship between the cytotoxicity produced by PE5 and its ability to reach the nucleus. First, we show that this enzyme, when incubated with HeLa cells, specifically cleaves nuclear RNA while it leaves cytoplasmic RNA unaffected. On the other hand, we have created new variants in which the residues of the nuclear localization signal that are important for the nuclear transport have been replaced. As expected, the individual changes produce a significant decrease in the cytotoxicity of the resulting variants. We conclude that the nuclear transport of PE5 is critical for its cytotoxicity. Therefore, routing a ribonuclease to the nucleus is an alternative strategy to endow it with cytotoxic activity. PMID- 20352291 TI - Novel combretastatin A-4 derivative XN0502 induces cell cycle arrest and apoptosis in A549 cells. AB - Combretastatin A-4 (CA-4) is a tubulin-binding compound currently in phase II trial as a tumor vascular-targeting agent. The present study evaluates the anti tumor activities and establishes the mechanism of the action of 4-(4 methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-pyrazol-3-amine(XN0502), a novel synthesized CA-4 analogue, in an effort towards finding the favorable therapeutics of CA-4 derivatives. XN0502 is characterized by its more potent anti proliferative activities against non-small cell lung cancer A549 cells (IC(50): 1.8 +/- 0.6 microM), than that on the normal human liver HL-7702 cells (IC(50): 9.1 +/- 0.4 microM). Of note, using tubulin polymerization assay, western blot and immuofluorescence analyses, XN0502 was showed to inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further studies indicated that XN0502 induced time- and dose-dependent G2/M arrest, accompanying with the reduction of CDC2/p34 expression and the downregulation of CDK7. The protein level alteration and the nuclear translocation of cyclinB1 were observed, denoting the M phase arrest in XN0502-treated cells. Moreover, XN0502 caused caspase-mediated apoptosis, as indicated by the cleavage of PARP, the reduction of procaspase-3 and procaspase-9, and the down-regulation of XIAP. Taken together, the current study demonstrates that the novel CA-4 analogue XN0502 is a promising anti-cancer agent with potent G2/M arrest- and apoptotic-inducing activities via targeting tubulin deserving further research and development, and helps provide data for exploiting new CA-4 analogues. PMID- 20352292 TI - 5k, a novel beta-O-demethyl-epipodophyllotoxin analogue, inhibits the proliferation of cancer cells in vitro and in vivo via the induction of G2 arrest and apoptosis. AB - Etoposide (VP-16), a topoisomerase II (Topo II) inhibitor, has been widely used to treat malignancies. Its clinical application, however, has been hindered by the rise of acquired multidrug resistance (MDR). Here, we report that 4beta-{[4 (pyrrolidin-1-ylmethyl)phenyl]amino}-4'-O-Demethyl-4-Epipodophyllotoxin (5k), a novel beta-O-demethyl-epipodophyllotoxin analogue, possesses higher antitumor activity than its parent compound (VP-16) in a panel of various human tumor cell lines. More importantly, it was also effective against MDR cells both in vitro and in vivo. Using a KB/VCR MDR tumor xenograft model that overexpresses P-gp, 5k (2.5 mg/kg) exhibited a 2.4-fold higher growth inhibition rate versus VP-16 (5 mg/kg). In contrast, 5k and VP-16 displayed similar antitumor activities in a KB tumor xenograft model. Molecular and cellular mechanism studies revealed that 5k targeted Topo II by trapping DNA-Topo II cleavage complexes that could directly cause DNA damage. There were two distinct cellular responses to DNA damage elicited by the treatment with 5k: at low concentrations (20-80 nM), mitotic entry was arrested through the suppression of the activity of Cyclin B1/Cdc 2 complexes via the ATM/ATR signaling pathway; at high concentrations (1.25-5.00 MUM), 5k-induced apoptotic signaling was mediated by the mitochondrial death pathways. Collectively, these data demonstrate the potential value of 5k as an antitumor drug candidate that should be further developed. PMID- 20352293 TI - A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis. AB - PURPOSE: Pancreatic cancer is the fourth leading cause of cancer death in the United States, and new drugs to treat the disease are needed. Pancreatic cancer cells are highly metastatic and exhibit resistance to apoptosis. Small molecules that can restore sensitivity to apoptosis or reduce metastasis would have therapeutic potential against this disease. Manzamine A is an alkaloid isolated from marine sponges that was suspected to have inhibitory activity against the mitogen activated kinase kinase (MEK). Because of this, the effects of Manzamine A were studied in pancreatic cancer cells. METHODS: AsPC-1 cells were treated for 48 h in the presence of various concentrations of Manzamine A and their phenotype, cytotoxicity, cell invasion and susceptibility to apoptosis were observed. RESULTS: Manzamine A decreased single cell formation, abrogated cell migration and restored the susceptibility of the cells to TRAIL-induced apoptosis in AsPC-1 cells. Its mechanism of action remains unknown, as manzamine A does not inhibit MEK. CONCLUSIONS: Manzamine A appears to have a formerly unrecognized activity in blocking tumor cell invasion as well as in restoring cancer cell susceptibility to apoptosis in vitro and therefore has the potential to be used as an adjuvant to existing cancer therapies. PMID- 20352294 TI - Phase I study of pemetrexed and pegylated liposomal doxorubicin in patients with refractory breast, ovarian, primary peritoneal, or fallopian tube cancer. AB - PURPOSE: Pemetrexed and pegylated liposomal doxorubicin (PLD) are clinically active as single agents and preclinically synergistic. This phase I, open-label trial evaluated the maximum tolerated dose (MTD) and safety of pemetrexed followed by PLD in patients with breast or gynecologic cancers. PATIENTS: Using 3 + 3 dose escalation, cohorts of 3-9 patients received escalating doses of pemetrexed 400-500 mg/m(2) on days 1 and 15 and PLD 30-45 mg/m(2) on day 1 of a 28-day cycle. All patients received folic acid and vitamin B(12) until 21 days after last pemetrexed dose. Patients continued until dose-limiting toxicity (DLT) or progression (PD). RESULTS: From 11/05 to 2/08, 29 patients entered treatment; median age: 60.6 years (range, 47.5-80.1); ECOG PS 0/1: 27.6%/72.4%; primary disease site: ovarian (55.2%), breast (34.5%), peritoneum (10.3%); prior therapies: chemotherapy (100.0%), surgery (72.4%), hormones/biologics (35%), and radiation (20.7%). Pemetrexed/PLD dose levels: L1 = 400/30 (n = 4), L2 = 400/35 (n = 6), L3 = 500/35 (n = 9), L4 = 500/40 (n = 7), and L5 = 500/45 (n = 3). Treatment-related grade 3-4 toxicities: hematologic-neutropenia (86.2%), leukopenia (58.6%), thrombocytopenia (48.3%), anemia (41.4%); nonhematologic mucosal inflammation (24.1%), febrile neutropenia (24.1%), hand-foot syndrome (13.8%), hypokalaemia (10.3%). Reasons for discontinuation: PD (48.3%), toxicity (27.6%), patient request (13.8%), and investigator request (10.3%). EFFICACY: 5 ovarian patients (20.8%) achieved partial response; median time to progression (TTP) was 6.1 months (range, 1.2-12.5). CONCLUSION: Pemetrexed plus PLD was reasonably tolerated in this heavily-pretreated population. MTD: pemetrexed 500 mg/m(2) and PLD 40 mg/m(2) may be carried forward to phase II studies in specific patient populations. TTP in platinum-refractory ovarian patients was greater than expected. PMID- 20352295 TI - The effect of CH3, F and NO2 substituents on the individual hydrogen bond energies in the adenine-thymine and guanine-cytosine base pairs. AB - The substituent effects on the geometrical parameters and the individual hydrogen bond (HB) energies of base pairs such as X-adenine-thymine (X-A-T), X-thymine adenine (X-T-A), X-guanine-cytosine (X-G-C), and X-cytosine-guanine (X-C-G) have been studied by the quantum mechanical calculations at the B3LYP and MP2 levels with the 6-311++G(d,p) basis set. The electron withdrawing (EW) substituents (F and NO(2)) increase the total binding energy (DeltaE) of X-G-C derivatives and the electron donating (ED) substituent (CH(3)) decreases it when they are introduced in the 8 and 9 positions of G. The effects of substituents are reversed when they are located in the 1, 5, and 6 positions of C, with exception of CH(3) in the 1 position and F in the 5 position, which in both cases the DeltaE value decreases negligibly small. With minor exceptions (X=8-CH(3), 8-F, and 9-NO(2)), both ED and EW substituents increase slightly the DeltaE values of X-A-T derivatives. The individual HB energies (E (HB)s) have been estimated using electron densities that calculated at the hydrogen bond critical points (HBCPs) by the atoms in molecules (AIM) method. Most of changes of individual HBs are in consistent with the ED/EW nature of substituents and the role of atoms entered H bonding. The remarkable change is observed for NO(2) substituted derivative in each case. PMID- 20352296 TI - Prediction of tautomer ratios by embedded-cluster integral equation theory. AB - The "embedded cluster reference interaction site model" (EC-RISM) approach combines statistical-mechanical integral equation theory and quantum-chemical calculations for predicting thermodynamic data for chemical reactions in solution. The electronic structure of the solute is determined self-consistently with the structure of the solvent that is described by 3D RISM integral equation theory. The continuous solvent-site distribution is mapped onto a set of discrete background charges ("embedded cluster") that represent an additional contribution to the molecular Hamiltonian. The EC-RISM analysis of the SAMPL2 challenge set of tautomers proceeds in three stages. Firstly, the group of compounds for which quantitative experimental free energy data was provided was taken to determine appropriate levels of quantum-chemical theory for geometry optimization and free energy prediction. Secondly, the resulting workflow was applied to the full set, allowing for chemical interpretations of the results. Thirdly, disclosure of experimental data for parts of the compounds facilitated a detailed analysis of methodical issues and suggestions for future improvements of the model. Without specifically adjusting parameters, the EC-RISM model yields the smallest value of the root mean square error for the first set (0.6 kcal mol(-1)) as well as for the full set of quantitative reaction data (2.0 kcal mol(-1)) among the SAMPL2 participants. PMID- 20352297 TI - Warfarin: history, tautomerism and activity. AB - The anticoagulant drug warfarin, normally administered as the racemate, can exist in solution in potentially as many as 40 topologically distinct tautomeric forms. Only 11 of these forms for each enantiomer can be distinguished by selected computational software commonly used to estimate octanol-water partition coefficients and/or ionization constants. The history of studies on warfarin tautomerism is reviewed, along with the implications of tautomerism to its biological properties (activity, protein binding and metabolism) and chemical properties (log P, log D, pK (a)). Experimental approaches to assessing warfarin tautomerism and computational results for different tautomeric forms are presented. PMID- 20352298 TI - Short-term weight change and fluctuation as risk factors for type 2 diabetes in Finnish male smokers. AB - Risk of weight change and fluctuation for type 2 diabetes was studied in a prospective study among 20,952 Finnish male smokers aged 50-69 years. Baseline data on lifestyle and medical history were collected, and height and weight measured. Weight was measured thrice after the baseline, 1 year apart. Weight change was defined as the slope of the regression line fitted to the four measurements and weight fluctuation as the root-mean-square-error deviation from this line. Incident cases of diabetes were identified from a national medication reimbursement register; 535 cases up to 9 years' follow-up. The Cox proportional hazards model served to estimate relative risk [RR, 95% confidence interval (CI)]. Weight gain and fluctuation associated with higher risk for diabetes, multivariate RR = 1.77, 95% CI 1.44-2.17, for weight gain of at least 4 kg compared with those of weight change less than 4 kg, and RR = 1.64, 95% CI 1.24 2.17 in the highest weight fluctuation quintile compared to the lowest. These RRs remained similar when weight change and fluctuation were adjusted for each other. Large weight fluctuation increased the risk of diabetes both in men who gained weight (>or=4 kg), had stable weight (+/- <4 kg), and lost weight (>or=4 kg); RR = 2.17, 95% CI 1.60-2.94, RR = 1.47, 95% CI 1.14-1.91, and RR = 2.04, 95% CI 1.47 2.83, respectively, compared to those with stable weight and moderate fluctuation. Short-term weight gain and large weight fluctuation are independent risk factors for diabetes. PMID- 20352299 TI - Microstructure and corrosion properties of as sub-rapid solidification Mg-Zn-Y-Nd alloy in dynamic simulated body fluid for vascular stent application. AB - Magnesium alloy stent has been employed in animal and clinical experiment in recent years. It has been verified to be biocompatible and degradable due to corrosion after being implanted into blood vessel. Mg-Y-Gd-Nd alloy is usually used to construct an absorbable magnesium alloy stent. However, the corrosion resistant of as cast Mg-Y-Gd-Nd alloy is poor relatively and the control of corrosion rate is difficult. Aiming at the requirement of endovascular stent in clinic, a new biomedical Mg-Zn-Y-Nd alloy with low Zn and Y content (Zn/Y atom ratio 6) was designed, which exists quasicrystals to improve its corrosion resistance. Additionally, sub-rapid solidification processing was applied for preparation of corrosion-resisting Mg-Zn-Y-Nd and Mg-Y-Gd-Nd alloys. Compared with the as cast sample, the corrosion behavior of alloys in dynamic simulated body fluid (SBF) (the speed of body fluid: 16 ml/800 ml min(-1)) was investigated. The results show that as sub-rapid solidification Mg-Zn-Y-Nd alloy has the better corrosion resistance in dynamic SBF due to grain refinement and fine dispersion distribution of the quasicrystals and intermetallic compounds in alpha-Mg matrix. In the as cast sample, both Mg-Zn-Y-Nd and Mg-Y-Gd-Nd alloys exhibit poor corrosion resistance. Mg-Zn-Y-Nd alloy by sub-rapid solidification processing provides excellent corrosion resistance in dynamic SBF, which open a new window for biomedical materials design, especially for vascular stent application. PMID- 20352300 TI - Potentiation of cell invasion and matrix metalloproteinase production by alpha3beta1 integrin-mediated adhesion of gastric carcinoma cells to laminin-5. AB - We previously reported that the adhesion of gastric carcinoma cells to the peritoneum mediated by the alpha3beta1 integrin-laminin interaction is a key step in the initial process of peritoneal metastatic dissemination. Carcinoma cells subsequently invade through the intercellular gaps of mesothelial linings. In this study, we examined the role of the interaction of carcinoma cells with laminin-5, which is a major component of submesothelial basement membranes and serves as a high-affinity ligand for alpha3beta1 integrin, in carcinoma cell invasion. Human gastric carcinoma cell lines (MKN1, GT3TKB, and NUGC-4) adhered in an alpha3beta1 integrin-dependent manner to the extracellular matrix deposited by peritoneal mesothelial cells. An in vitro invasion assay using the Boyden chamber system revealed that MKN1 cell migration through the membranes increased when the membranes were coated with matrices produced by mesothelial cells or with laminin-5-containing Matrigel as compared to Matrigel alone. The cell migration promoted by laminin-5-containing Matrigel was inhibited by the presence of anti-alpha3 integrin antibody. When MKN1 cells were cultured in a laminin-5 coated plate, these cells were promoted to produce matrix metalloproteinase (MMP) 9, as assessed by gelatin zymography, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. These results suggest that the production of MMP-9 by MKN1 cells was potentiated by the alpha3beta1 integrin laminin-5 interaction, which facilitated their invasion via degradation of the matrix. PMID- 20352301 TI - Flight initiation by male Rhodnius prolixus is promoted by female odors. AB - Several triatomine bug species utilize chemical cues for sexual communication. We tested whether female or male Rhodnius prolixus, a vector of Chagas disease, produce volatile chemicals that elicit flight responses from conspecifics, and then isolated the source of the chemical. Males confronted with an airstream containing female odors showed a significantly greater take-off frequency compared to a blank airstream or an airstream with male odors. In contrast, females exhibited similar take-off frequencies to male or female odor as to a clean airstream. Occlusion of female metasternal glands with paraffin wax resulted in a significant decrease in male take-off frequency compared to that of intact females. Additionally, excised female metasternal glands elicited a similar take-off frequency from males as did intact females, both significantly greater than the take-off frequency to clean air. These results show that R. prolixus females release a pheromone from their metasternal glands that causes upwind flight in conspecific males. PMID- 20352302 TI - Measuring clients' perception of functional limitations using the Perceived Functioning & Health questionnaire. AB - BACKGROUND: The Perceived Functioning & Health (PFH) questionnaire was developed to collect, in a standardized manner, which work activities are limited due to health conditions according to the perception of the client. In this study the questionnaire's reliability and validity are investigated. METHODS: The PFH questionnaire is comprised of 147 questions, distributed over 33 scales, pertaining to the client's psychosocial and physical work limitations. The PFH data of 800 respondents were analyzed: 254 healthy employees, 408 workers on sick leave and 138 recipients of a disability pension. Internal consistency (Cronbach's alpha) for the scales was established. The test-retest reliability was examined for the data of 52 recipients of a disability pension who filled out the PFH twice within an interval of 1 month. Validation was established by taking the nature of the limitations as a criterion: mental limitations, physical limitations or a mix of both. To this end, the respondents were divided into groups distinguished on the basis of self-classification, as well as classification on the basis of disease codes given by insurance and occupational health physicians: a "healthy" group, subjects with only physical ("physical" group) or mental limitations ("mental" group) or mixed limitations ("mixed" group). The scale scores of these groups were compared and tested using analyses of-variance and discriminant analyses. RESULTS: The scales were found to have sufficient to good internal consistency (mean Cronbach's-alpha = 0.79) and test retest reliability (mean correlation r = 0.76). Analyses-of-variance demonstrated significant differences between the scores of the mental, physical and healthy groups on most of the expected scales. These results were found both in groups defined by self-classification as well as in groups based on disease codes. Moreover, discriminant analyses revealed that the a priori classification of the respondents into three groups (mental, physical, healthy) for more than 75% of them corresponded with the classification on the basis of scale scores obtained from the questionnaire. Furthermore, limitations due to specific types of complaints (low back pain, fatigue, concentration problems) or diagnosed disorders (musculoskeletal disorders, reactive disorders, endogenous disorders) were clearly reflected in the scores of the related scales of the PFH. CONCLUSION: The psychometric properties of the PFH with respect to reliability and validity were satisfactory. The PFH would appear to be an appropriate instrument for systematically measuring functional limitations in subjects on sick leave and in those receiving disability pensions, and could be used as a starting point in a disability claim procedure. PMID- 20352303 TI - Fluorescent carbon dots capped with PEG200 and mercaptosuccinic acid. AB - The synthesis and functionalization of carbon nanoparticles with PEG(200) and mercaptosuccinic acid, rendering fluorescent carbon dots, is described. Fluorescent carbon dots (maximum excitation and emission at 320 and 430 nm, respectively) with average dimension 267 nm were obtained. The lifetime decay of the functionalized carbon dots is complex and a three component decay time model originated a good fit with the following lifetimes: tau(1) = 2.71 ns; tau(2) = 7.36 ns; tau(3) = 0.38 ns. The fluorescence intensity of the carbon dots is affected by the solvent, pH (apparent pK(a) of 7.4 +/- 0.2) and iodide (Stern Volmer constant of 78 +/- 2 M(-1)). PMID- 20352305 TI - Azo-hydrazo tautomerism and inclusion complexation of 1-phenylazo-2-naphthols with various solvents and beta-cyclodextrin. AB - Spectral characteristics of sudan I (SDI), sudan II (SDII) and mordant violet-5 (MV5) have been studied in various solvents and beta-cyclodextrin (beta-CD). The inclusion complex of the above molecules with beta-CD was analyzed by UV-visible, fluorometry, and DFT methods. The solvent study shows that azo-hydrazo tautomer is present in these molecules. The increase in the fluorescence intensity and a large bathochromic shift in the S(1) state indicate these molecules forms 1:1 inclusion complex with beta-CD. PMID- 20352304 TI - Effect of 1-aminoanthracene (1-AMA) binding on the structure of three lipocalin proteins, the dimeric beta lactoglobulin, the dimeric odorant binding protein and the monomeric alpha1-acid glycoprotein. Fluorescence spectra and lifetimes studies. AB - We studied effect of 1-aminoanthracene (1-AMA) binding on the structures of dimeric beta lactoglobulin, dimeric odorant binding protein (OBP) and monomeric alpha(1)-acid glycoprotein (lipocalin family proteins) by monitoring fluorescence excitation spectra and measuring fluorescence lifetimes of the tryptophan residues of the proteins. Results show that binding of 1-AMA to beta lactoglobulin and OBP modifies their conformation even at low probe concentration compared to that of the proteins. Structural modification induces a red shift of the fluorescence excitation spectra maximum of tryptophan residues accompanied with an increase of the third fluorescence lifetime and a decrease of its pre exponential factor. These effects were not observed for alpha(1)-acid glycoprotein, probably as the result of carbohydrate presence. These data raise doubts concerning use of 1-AMA as a probe to study biological properties of beta lactoglobulin and OBP. PMID- 20352306 TI - Intense white luminescence from combustion synthesized Ca12Al14O33:Yb(3+)/Yb(2+) single phase phosphor. AB - The Ca(12)Al(14)O(33):Yb(3+)/Yb(2+) single phase nano-phosphor has been synthesized through combustion route and its luminescence and lifetime studies have been carried out up to 20 K using 976 and 266 nm excitations. The samples heated in open atmosphere have shown the presence of Yb in Yb(3+) and Yb(2+) states. The 976 nm excitation results a cooperative upconversion emission at 486 nm due to the Yb(3+) state and a broad band in the blue region and has been assigned to arise from the defect centers. The 266 nm excitation on the other hand results a broad emission band even from as-synthesized phosphor without doping of Yb, the width of which increases in presence of Yb due to the emission from Yb(2+) ions formed in heated samples. The white emission covers almost whole visible region with bandwidth 190 nm. The ions in Yb(2+) state has been found to increase with the increase in heating temperature up to 1,273 K. A back conversion of Yb(2+) to Yb(3+) has been observed for higher temperatures. Effect of boric and phosphoric acids as flux on the emission properties of Yb(3+) and Yb(2+) states have been examined and discussed. Quantum yield of emission has also been determined for different samples. PMID- 20352307 TI - The use of DRAQ5 to monitor intracellular DNA in Escherichia coli by flow cytometry. AB - Flow cytometry provides a rapid and high-content multiparameter analysis of individual microorganisms within a population. In the past years, several fluorescent stains were developed in order to monitor DNA content distribution and cell-cycle phases, mainly in eukaryotic cells. Recently, due to its low detection limits, several of these fluorescent stains were also applied to prokaryotic cells. In this study, the ability of a novel far-red fluorescent stain DRAQ5 in assessing intracellular DNA content distribution in Escherichia coli DH5alpha was evaluated. The results showed that a DRAQ5-labelled live E. coli suspension can be obtained by incubation of 1 x 10(6) cells/mL with 5 microM DRAQ5 in PBS buffer supplemented with EDTA (pH = 7.4) during 30 min at 37 degrees C. Flow cytometric analysis of fixed E. coli cells revealed that ethanol should be used in detriment of glutaraldehyde for DRAQ5 labelling. After the analysis of RNase and DNase digested samples, DRAQ5 was proven to be a specific DNA labelling stain. The present study demonstrates that the use of DRAQ5 as a DNA-labelling stain provides an easy assessment of intracellular DNA content and cell-cycle phases in gram-negative bacteria such as E. coli. PMID- 20352308 TI - Synthesis, characterization, DNA binding properties, fluorescence studies and antioxidant activity of transition metal complexes with hesperetin-2-hydroxy benzoyl hydrazone. AB - A novel Schiff-base ligand (H(5)L), hesperetin-2-hydroxy benzoyl hydrazone, and its copper (II), zinc (II) and nickel (II) complexes (M.H(3)L) [M(II) = Cu, Zn, Ni], have been synthesized and characterized. The ligand and Zn (II) complex exhibit green and blue fluorescence under UV light and the fluorescent properties of the ligand and Zn (II) complex in solid state and different solutions were investigated. In addition, DNA binding properties of the ligand and its metal complexes have been investigated by electronic absorption spectroscopy, fluorescence spectra, ethidium bromide displacement experiments, iodide quenching experiments, salt effect and viscosity measurements. Results suggest that all the compounds bind to DNA via an intercalation binding mode. Furthermore, the antioxidant activity of the ligand and its metal complexes was determined by superoxide and hydroxyl radical scavenging methods in vitro. The metal complexes were found to possess potent antioxidant activity and be better than the free ligand alone and some standard antioxidants like vitamin C and mannitol. PMID- 20352309 TI - Considerations for the impact of personal genome information: a study of genomic profiling among genetics and genomics professionals. AB - With the expansion of genomic-based clinical applications, it is important to consider the potential impact of this information particularly in terms of how it may be interpreted and applied to personal perceptions of health. As an initial step to exploring this question, we conducted a study to gain insight into potential psychosocial and health motivations for, as well as impact associated with, undergoing testing and disclosure of individual "variomes" (catalogue of genetic variations). To enable the collection of fully informed opinions, 14 participants with advanced training in genetics underwent whole-genome profiling and received individual reports of estimated genomic ancestry, genotype data and reported disease associations. Emotional, cognitive and health behavioral impact was assessed through one-on-one interviews and questionnaires administered pre testing and 1-week and 3-months post-testing. Notwithstanding the educational and professional bias of our study population, the results identify several areas of research for consideration within additional populations. With the development of new and less costly approaches to genome risk profiling, now available for purchase direct-to-consumers, it is essential that genome science research be conducted in parallel with studies assessing the societal and policy implications of genome information for personal use. PMID- 20352310 TI - Exposure to community violence and protective and risky contexts among low income urban African American adolescents: a prospective study. AB - This study examined protective and risky companionship and locations for exposure to community violence among African American young adolescents living in high crime, urban areas. The Experience Sampling Method (ESM), an in vivo data collection method, was employed to gather information from 233 students (62% female) over 3 years, beginning in the 6th grade. Questionnaire variables of exposure to community violence were regressed onto ESM companionship and location variables, cross-sectionally and longitudinally, separately for boys and girls. At different points, time spent with parents, in school, and outside in private space was associated with less exposure to violence for boys and girls, while time spent with girls was protective for boys. In addition, time spent outside in public and with older peers was associated with increased risk for boys and girls. These findings are discussed in relation to previous and potential future research, and to strategies to prevent exposure to community violence. PMID- 20352311 TI - Relationships between level and change in family, school, and peer factors during two periods of adolescence and problem behavior at age 19. AB - While prior research has examined family, school, and peer factors as potential predictors of problem behavior, less attention has been given to studying when these factors are most predictive of problems and if and when changes in these factors signal risk. Using annual data on a community sample of 1,040 individuals (47% female; 81% White), this study models growth in risk and protective factors during two developmental periods (Grades 5-8 and Grades 9-12) in order to predict substance misuse and crime at age 19. For protective factors of positive relationships with family and positive bonds to school, both the levels of these factors at Grade 5 and change between Grade 5 and Grade 8 predicted substance misuse and crime in early adulthood. Higher likelihoods of both forms of problem behavior also were predicted by increases in the risk factor of exposure to negative peers between 5th and 8th grade. In the late adolescent period, levels at 9th grade of all risk and protective factors examined predicted both substance misuse and crime. Also, increases in exposure to negative peers in late adolescence predicted greater likelihoods of both forms of problem behavior, while greater risk of substance misuse was predicted by decreases in school bonding and academic achievement, and greater risk of crime was predicted by worsening relationships with family. The results add to prior research by indicating that in addition to the level, change in risk and protective factors during these two stages of development can be signals of risk and are promising targets for intervention. PMID- 20352312 TI - Parent and emergency physician comfort with a system of on-line emergency-focused medical summaries for infants with significant cardiac disease. AB - Surveys were developed and administered to assess parental comfort with emergency care for children with special health care needs (CSHCN) with cardiac disease and the impact of a web-based database of emergency-focused clinical summaries (emergency information forms-EIF) called Midwest Emergency Medical Services for Children Information System (MEMSCIS) on parental attitudes regarding emergency care of their CSHCN. We hypothesized that MEMSCIS would improve the parent and provider outlook regarding emergencies of young children with heart disease in a randomized controlled trial. Children under age 2 were enrolled in MEMSCIS by study nurses associated with pediatric cardiac centers in a metropolitan area. Parents were surveyed at enrollment and 1 year on a 5-Point Likert Scale. Validity and reliability of the survey were evaluated. Study nurses formulated the emergency-focused summaries with cardiologists. One-hundred-seventy parent subjects, 94 study and 76 control, were surveyed at baseline and 1 year. Parents felt that hospital personnel were well-prepared for emergencies of their children and this improved from baseline 4.07 +/- 1.03 to 1 year 4.24 +/- 1.04 in study parents who had an EIF for their child and participated in the program (p = 0.0114) but not control parents. Parents perceived an improved comfort level by pre-hospital (p = 0.0256) and hospital (p = 0.0031) emergency personnel related to the MEMSCIS program. The MEMSCIS Program with its emergency-focused web-based clinical summary improved comfort levels for study parents. We speculate that the program facilitated normalization for parents even if the EIF was not used in an emergency during the study. The MEMSCIS program helps to prepare the family and the emergency system for care of CSHCN outside of the medical home. PMID- 20352313 TI - The PACIFIC (Prevention of AtherothrombotiC Incidents Following Ischemic Coronary attack) Registry: Rationale and design of a 2-year study in patients initially hospitalised with acute coronary syndrome in Japan. AB - PURPOSE: Atherothrombotic disease is a major and increasing health problem in Japan. Effective secondary prevention of atherothrombotic events after acute coronary syndrome (ACS) is required, but clinical evidence regarding the current state of preventive treatment and the rate of subsequent atherothrombotic events after ACS in Japan is limited. Up-to-date Japanese epidemiological real world data are required to construct optimal evidence-based Japanese guidelines for the management of patients with ACS. METHODS: The PACIFIC (Prevention of AtherothrombotiC Incidents Following Ischemic Coronary attack) Registry is an ongoing, observational study of a large cohort of Japanese patients hospitalised with any manifestation of ACS (ST-segment elevation myocardial infarction, non-ST segment elevation myocardial infarction or unstable angina [UA]). Up to 4,000 patients from approximately 100 sites nationwide will be enrolled and the primary study endpoint is the incidence of any major atherothrombotic event (cardiovascular, cerebrovascular or peripheral) between the initial ACS event and 2 years of follow-up. Secondary endpoints include fatal myocardial infarction (MI), fatal stroke, other cardiovascular death, non-cardiovascular death, non fatal MI/UA, non-fatal stroke and acute peripheral arterial occlusion. Hospitalisation for vascular interventions will also be recorded, as will haemorrhage requiring hospitalisation or blood transfusion. The use of preventive treatment will also be reported and different patient subgroups (diabetes mellitus, hypertension, dyslipidaemia and metabolic syndrome) will be analysed. It is expected that the study will be completed in early to mid 2011. CONCLUSIONS: The PACIFIC Registry will give insights as to the Japanese epidemiology of ACS: recurrence of atherothrombotic events in the same or other vascular territories. PMID- 20352315 TI - Antioxidant enzyme activity and lipid peroxidation in the blood of rats co treated with vanadium (V(+5)) and chromium (Cr (+3)). AB - Selected biochemical parameters were studied in the blood of outbred, male Wistar rats which daily received to drink deionized water (Group I, control) or solutions of: sodium metavanadate (SMV; 0.100 mg V/mL)-Group II; chromium chloride (CC; 0.004 mg Cr/mL)-Group III; and SMV-CC (0.100 mg V and 0.004 mg Cr/mL)-Group IV for a 12-week period. The diet and fluid intake, body weight gain, and food efficiency ratio (FER) diminished significantly in the rats of Groups II and IV, compared with Groups I and III. The plasma total antioxidant status (TAS) as well as the MDA and the L: -ascorbic acid level in the erythrocytes (RBCs) remained unchanged in all the groups, whereas the plasma L: ascorbic acid concentration decreased markedly in Group II, compared with Group III. The activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT), cellular glutathione peroxidase (cGSH-Px), and glutathione reductase (GR) in RBCs remained unaltered in all the treated rats. However, the activity of glutathione S-transferase (GST) and the content of reduced glutathione (GSH) in RBCs decreased and increased, respectively, in Groups II, III, and IV, compared with Group I. A vanadium-chromium interaction which affected the GST activity was also found. To summarize, SMV and CC administered separately or in combination in drinking water for 12 weeks did not alter either lipid peroxidation (LPO) or the activities of Cu,Zn-SOD, CAT, cGSH-Px, and GR, which allows a conclusion that both metals in the doses ingested did not reveal their pro-oxidant potential on RBCs. PMID- 20352314 TI - Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. AB - BACKGROUND: Beta-blockers are mainstay of current treatment of heart failure (HF). Beta-adrenergic receptors (AR) single nucleotide gene polymorphisms (SNPs) may influence the sensitivity and density of beta-AR. We assessed the relation between three common beta-AR SNPs and the response to carvedilol administration. METHODS AND RESULTS: We studied 183 consecutive patients with chronic HF due to ischemic or nonischemic cardiomyopathy, a LV ejection fraction (LVEF) < or = 0.35, not previously treated with beta-blockers. Each patient underwent gated SPECT radionuclide ventriculography, cardiopulmonary exercise testing and invasive hemodynamic monitoring at baseline and after 12 months of carvedilol administration at maintenance dosages. The beta1-AR gene Arg389Gly and the beta2 AR gene Arg16Gly SNPs were not related to the response to carvedilol administration. Homozygotes for the Glu27Glu allele showed a greater increase in the LVEF, compared to the other patients (+13.0 +/- 12.2% versus +7.1 +/- 8.1% in the Gln27Gln homozygotes, and 8.3 +/- 11.4% units in the Gln27Glu heterozygotes; p = 0.022 by ANOVA). Glu27Glu homozygotes also showed a greater decline in the pulmonary wedge pressure both at rest and at peak exercise. Gln27Glu SNP was selected amongst the determinants of the LVEF response to carvedilol at multivariable analysis, in addition to the cause of cardiomyopathy, baseline systolic blood pressure and the dose of carvedilol administered. CONCLUSION: Beta1-AR Arg389Gly and beta2-AR Arg16Gly SNPs are not related to the response to carvedilol therapy. In contrast, the Gln27Glu SNP is a determinant of the LVEF response to this agent in patients with chronic HF. PMID- 20352316 TI - Self-esteem in HIV-positive and HIV-negative gay and bisexual men: implications for risk-taking behaviors with casual sex partners. AB - Research suggests that self-esteem in gay and bisexual men may be linked with sexual risk-taking behaviors. As part of a larger investigation into the sexual practices of gay and bisexual men, we assessed serostatus, self-esteem, condom use, and HIV disclosure to sexual partners. Among HIV-negative men, no relationships were found between their self-esteem and tendency to discuss their and their partners' HIV status. However, among HIV-positive men, there was a positive relationship between self-esteem and disclosure to receptive and insertive anal sex partners. These results suggest greater attention to the self esteem of HIV-positive men by attending healthcare workers and social support groups. PMID- 20352317 TI - Physiological and psychosocial factors that predict HIV-related fatigue. AB - Fatigue is one of the most common and debilitating symptoms experienced by HIV infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue. PMID- 20352318 TI - Vaginal practices and associations with barrier methods and gel use among Sub Saharan African women enrolled in an HIV prevention trial. AB - Vaginal practices may interfere with the use and/or the effectiveness of female initiated prevention methods. We investigated whether vaginal practices differed by randomization group in a phase III trial of the diaphragm with lubricant gel (MIRA) in Sub-Saharan Africa (n = 4925), and if they were associated with consistent use of study methods. At baseline, vaginal practices were commonly reported: vaginal washing (82.77%), wiping (56.47%) and insertion of dry or absorbent materials (20.58%). All three practices decreased during the trial. However, women in the intervention group were significantly more likely to report washing or wiping during follow-up compared to those in the control group. Additionally, washing, wiping, and insertion, were all independently and inversely associated with consistent diaphragm and gel use and with condom use as well, regardless of study arm. A better understanding of the socio-cultural context in which these practices are embedded could improve educational strategies to address these potentially modifiable behaviors, and may benefit future HIV prevention interventions of vaginal methods. PMID- 20352320 TI - Acceptability of a microenterprise intervention among female sex workers in Chennai, India. AB - Female sex workers have been central in India's HIV epidemic since it was first diagnosed among them in 1989. Female sex workers' risk of HIV is primarily economically motivated. The Pi pilot study examined the feasibility and association of a microenterprise intervention, the tailoring of canvas bags, on sexual risk behaviors among female sex workers (N = 100) in Chennai. Women were randomized to an intervention or control arm. Between-group comparisons at baseline and at six-month follow-up were performed. Multivariate linear regression with bootstrapping was conducted to estimate the intervention effect. At baseline, women were a median of 35 years old, 61% were married and they had an average of two children. Intervention participants reported a significantly lower number of sex partners and significant increases in income at the 6-month follow-up compared to control participants. In a multivariate model, intervention participants had a significantly lower number of paying clients per month at follow-up compared to control participants. By graduation, 75% of intervention arm participants had made at least one sellable canvas bag and 6 months after the study's end, 60% have continued involvement in bag production. The pilot study demonstrated that microenterprise interventions are successful in both providing FSWs with licit income opportunities and was associated with reductions in HIV risk behaviors. PMID- 20352319 TI - Determinants of optimal adherence over time to antiretroviral therapy amongst HIV positive adults in South Africa: a longitudinal study. AB - Highly active antiretroviral therapy (HAART) requires strict adherence to achieve optimal clinical and survival benefits. A study was done to explore the factors affecting HAART adherence among HIV positive adults by reviewing routinely collected patient information in the Centre for the AIDS Programme of Research in South Africa's (CAPRISA) AIDS Treatment Programme. Records of 688 patients enrolled between 2004 and 2006 were analysed. Patients were considered adherent if they had taken at least 95% of their prescribed drugs. Generalized estimating equations were used to analyse the data. The results showed that HAART adherence increased over time, however, the rate of increase differed by some of the socio demographic and behavioural characteristics of the patients. For instance, HAART adherence increased in both urban and rural treatment sites over time, but the rate of increase was higher in the rural site. This helped identify sub populations, such as the urban population, that required ongoing adherence counseling. PMID- 20352321 TI - Child and adolescent mental health services: issues and solutions. Introduction to special issue. PMID- 20352323 TI - The expression pattern of SEPT7 correlates with sperm morphology. AB - PURPOSE: To investigate the expression pattern of the SEPT7 protein during spermatogenesis and its potential role in sperm function. METHODS: We first investigated the expression pattern of SEPT7 during different steps of mouse spermiogenesis using an immunofluorescence assay (IFA). IFA was also applied to study the expression pattern of SEPT7 in human ejaculated spermatozoa. Nine fertile men with normal semen parameters were used as the control group, and 21 infertile men with asthenozoospermia were recruited as the patient group. We assessed the frequency of the SEPT7 signal in the various morphological subgroups. RESULTS: In humans, the frequency of a defective SEPT7 signal was significantly increased in men with asthenozoospermia. The absence of a SEPT7 signal was more prevalent in sperm containing morphological defects of various types. CONCLUSIONS: The expression pattern of SEPT7 suggested that this protein may be involved in the regulation of subcellular-compartment formation during spermiogenesis in the mouse. The absence of a SEPT7 signal correlated with multiple sperm defects. PMID- 20352324 TI - Explicit- and implicit bullying attitudes in relation to bullying behavior. AB - The main aim of this study was to examine whether an assessment of implicit bullying attitudes could add to the prediction of bullying behavior after controlling for explicit bullying attitudes. Primary school children (112 boys and 125 girls, M age = 11 years, 5 months) completed two newly developed measures of implicit bullying attitudes (a general Implicit Association Test on bullying and a movie-primed specific IAT on bullying), an explicit bullying attitude measure, and self reported, peer reported, and teacher rated bullying behavior. While explicit bullying attitudes predicted bullying behavior, implicit attitudes did not. However, a significant interaction between implicit and explicit bullying attitudes indicated that in children with relatively positive explicit attitudes, implicit bullying attitudes were important predictors of bullying behavior. Theoretical and practical implications are discussed. PMID- 20352326 TI - Getting the message across: does the use of drama aid education in palliative care? AB - Drama is a promising means of delivering educational messages in palliative care. Research studies have found drama to be an effective means of delivering educational messages in other domains of learning, such as teaching health education to children and adults and engaging the general public in health policy development. This paper discusses the potential of drama for palliative care education and provides an example of the use of a drama to deliver messages about death and dying at a conference on palliative care. The paper suggests a theoretical framework for how future drama productions could be developed to educate the community, health professionals and students about palliative care. PMID- 20352325 TI - Whole chromosome elimination and chromosome terminus elimination both contribute to somatic differentiation in Taiwanese hagfish Paramyxine sheni. AB - Chromosome elimination is a process in which some chromatins are discarded from the presumptive somatic cells during early embryogenesis. Eliminated chromatins in hagfish generally consist of repetitive sequences, and they are highly heterochromatinized in germ cells. In this study, we characterized four novel eliminated DNA families, EEPs1-4, from the Taiwanese hagfish Paramyxine sheni. Sequences of these four elements occupied 20-27% of eliminated DNA in total, and each family was arranged mainly in tandem in the germline genome with high copy numbers. Although most of these elements were eliminated, a minor fraction remained in somatic cells. Some eliminated DNA families are shared as eliminated sequences between Eptatretidae and Myxinidae. Fluorescence in situ hybridization (FISH) of these elements showed that not only heterochromatic chromosomes but also both ends of euchromatic chromosomes in germ cells are absent in somatic cells of P. sheni. It strongly suggests that chromosome terminus elimination, in addition to whole chromosome elimination, contributes to somatic chromosome differentiation. Telomere-FISH further showed that chromosome fragmentation and the subsequent de novo addition of telomeric repeats are the likely mechanisms underlying chromosome terminus elimination. These characteristics make it indispensable to study the evolution and mechanisms underlying chromosome elimination in hagfish. PMID- 20352327 TI - Response to the ration levels on growth, body composition, energy, and protein maintenance requirement of the Indian catfish (Heteropneustes fossilis-Bloch 1974). AB - An 8-week growth study was conducted to determine the effect of ration level, energy, and protein maintenance requirement of catfish, Heteropneustes fossilis Bloch, fingerling (7.90+/-0.55 cm; 3.10+/-0.28 g) by feeding casein-gelatin-based purified diet (40% CP; 3.61 kcal g-1 GE) at six ration levels 1-6% of BW/day, at 0800 and 1700 h, in triplicate, with 20 fish per trough fitted with water flow through system of volume 55 L. Maximum live weight gain, best feed conversion ratio (FCR), best specific growth rate (SGR), and highest protein efficiency ratio (PER) were evident for ration levels of 4-5% body weight. However, second degree polynomial regression analysis for weight gain, FCR, PER, protein, and energy retention data indicated that the break-points occurred at 5.08, 4.18, 4.05, 4.16, and 4.17% BW/day, respectively. Significantly (P<0.05) higher body protein content was recorded at 4 and 5% rations. While a linear increase in body fat content with inverse relationship in moisture content was evident with increasing rations. Ash content remained insignificantly (P>0.05) low at higher rations. Protein and energy retention values also produced significant (P<0.05) differences. Based on the results obtained, it is recommended that feeding in the range of 4 to 4.5% BW/day, corresponding to 1.60-1.80 g protein and 14.46-16.27 kcal energy g100 g(-1) of the diet/day is optimum for the growth and efficient feed utilization of H. fossilis, while 2-3% ration levels (0.80-1.20 g protein and 7.23-10.84 kcal energy) suggest that these amounts approximate to the maintenance requirement of this fish. PMID- 20352329 TI - Current situation and the development of the dairy industry in Jordan, Saudi Arabia, and Syria. AB - The development of the dairy industry plays an important role in the economy of Middle Eastern countries. Judged by its growth rate, the dairy industry is viewed as one of the most progressive food industries in the Middle East. During the early 1970s, countries established executive programs to promote dairy farming; the major objective was to attain self-sufficiency in milk production. A massive investment was set up for importing top class cattle, complying with top industry operating standards, and a simultaneous introduction of the latest technology in processing, packaging, and distributing. Milk production has grown tremendously at rates of 6.6% and 4.9% in Syria and Saudi Arabia, respectively, between 2002 and 2007, which resulted in these nations being almost self-sufficient. Regarding Jordan, milk production has not yet met this target. An excessive growth in the dairy industry is quite noticeable in this region with an expanding capacity for exports. The aim of this study is to show the most recent trends and future prospects of the dairy industries in Syria, Saudi Arabia, and Jordan. It also attempts to investigate the drivers for the development of milk production, consumption, and trade in the region. PMID- 20352328 TI - Efficient mammalian germline transgenesis by cis-enhanced Sleeping Beauty transposition. AB - Heightened interest in relevant models for human disease increases the need for improved methods for germline transgenesis. We describe a significant improvement in the creation of transgenic laboratory mice and rats by chemical modification of Sleeping Beauty transposons. Germline transgenesis in mice and rats was significantly enhanced by in vitro cytosine-phosphodiester-guanine methylation of transposons prior to injection. Heritability of transgene alleles was also greater from founder mice generated with methylated versus non-methylated transposon. The artificial methylation was reprogrammed in the early embryo, leading to founders that express the transgenes. We also noted differences in transgene insertion number and structure (single-insert versus concatemer) based on the influence of methylation and plasmid conformation (linear versus supercoiled), with supercoiled substrate resulting in efficient transpositional transgenesis (TnT) with near elimination of concatemer insertion. Combined, these substrate modifications resulted in increases in both the frequency of transgenic founders and the number of transgenes per founder, significantly elevating the number of potential transgenic lines. Given its simplicity, versatility and high efficiency, TnT with enhanced Sleeping Beauty components represents a compelling non-viral approach to modifying the mammalian germline. PMID- 20352330 TI - Effect of tropical browse leaves supplementation on rumen enzymes of sheep and goats fed Dichanthium annulatum grass-based diets. AB - In a switch-over experiment, eight male animals, four each of sheep and goats of local breeds with mean body weight of 26. 8 +/- 2.0 and 30.0 +/- 2.1 kg, were fed Dichanthium annulatum (DA) grass and four browse species viz. Helictris isora, Securengia virosa, Leucaena leucocephala (LL) and Hardwickia binnata (HB) in four feeding trials to assess their supplementary effect on activity of rumen enzymes. The sheep and goats were offered DA grass with individual browse in 75:25 and 50:50 proportions, respectively, for more than 3 months during each feeding trial, and rumen liquor samples were collected twice at 0 and 4 h post feeding after 60 and 90 days of feeding. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GDH) enzymes were determined in the bacteria and protozoa fractions of rumen liquor, while cellulase enzyme activity was measured in mixed rumen liquor. LL and HB had the highest and lowest contents of CP, while fibre contents were lower in early than later browse leaves. Supplementation of browse leaves significantly (P < 0.05) affect the specific activity of GDH enzyme in bacteria fraction of rumen liquor of animal species, while GDH activity was similar in protozoa fraction of rumen liquor of sheep and goats on all DA grass-browse-supplemented diets except DA-HB (42.8 units/mg protein), where activity was significantly (P < 0.05) low. Specific activities of GOT and GPT enzymes in both bacteria and protozoa fractions of rumen liquor differ significantly (P < 0.05) due to supplementation of browse leaves to DA grass. Browse leaves significantly (P < 0.05) affect the cellulase enzyme activity in animal rumen liquor, being highest on DA-LL (193.4) and lowest on DA-HB diet (144.8 microg sugar/mg protein). Goat exhibited higher activities of GOT and GPT than sheep in both bacteria and protozoa fraction of rumen liquor, while cellulase activity was similar between the animal species on the grass-browse leaves diets. Results indicate that browse leaves supplementation affect the enzyme activities of sheep and goats rumen, while the goats rumen liquor had higher activities of GOT, GPT and GDH enzyme than sheep. PMID- 20352331 TI - Individual and treatment setting predictors of HIV/AIDS knowledge among psychiatric patients and their implications in a national multisite study in Brazil. AB - The objective of this study is to measure HIV/AIDS knowledge among patients with mental illness in Brazil and to examine individual and treatment setting predictors of knowledge. We conducted a cross-sectional national multicenter study among 2,475 patients in 26 randomly selected mental health institutions throughout Brazil. We used Item Response Theory to standardize knowledge scores and multilevel multiple linear regression to determine the effect of individual and treatment setting characteristics on standardized knowledge score. Schizophrenia was the main diagnosis (48%) of participants. Mean knowledge score was 6.78 (range 1-10). Treatment setting characteristics were not associated with knowledge scores. Higher HIV/AIDS knowledge scores were significantly associated with a history of sexually transmitted disease (STD), previous HIV testing and consistent condom use; lower HIV/AIDS knowledge scores were significantly associated with specific sociodemographic, psychiatric, and HIV risk-perception factors. Psychiatric patients in Brazil lag behind the general population with knowledge scores comparable to those of nearly a decade ago. The mental health system in Brazil and elsewhere must consider strategies beyond dispensing information, for preventing HIV/AIDS transmission in the psychiatric population. PMID- 20352332 TI - Determinants of community coalition ability to support evidence-based programs. AB - This study examines how aspects of coalition functioning predict a coalition's ability to promote high-quality implementation of evidence-based programs (EBPs). The study involved 62 Communities That Care (CTC) coalitions in Pennsylvania measured annually from 2003 to 2007. Findings indicate that the communities with higher levels of poverty and longer existing coalitions are related to lower support for high-quality EBP implementation. Several aspects of coalition functioning-including higher levels of funding; leadership strength; board efficiency; strong internal and external relationships; and fidelity to the CTC model-significantly predicted support for high-quality EBP implementation. Earlier measurements of coalition functioning (2003-2004 and 2005-2006) predicted EBP implementation (2007) more strongly than concurrent coalition assessments (2007). The discussion focuses on how coalitions and technical assistance providers can improve coalition support for the implementation of EBPs. PMID- 20352333 TI - Incorporating autoregulatory mechanisms of the cardiovascular system in three dimensional finite element models of arterial blood flow. AB - The cardiovascular system is a closed-loop system in which billions of vessels interact with each other, and it enables the control of the systemic arterial pressure and varying organ flow through autoregulatory mechanisms. In this study, we describe the development of mathematical models of autoregulatory mechanisms for systemic arterial pressure and coronary flow and discuss the connection of these models to a hybrid numerical/analytic closed-loop model of the cardiovascular system. The closed-loop model consists of two lumped parameter heart models representing the left and right sides of the heart, a three dimensional finite element model of the aorta with coronary arteries, three element Windkessel models and lumped parameter coronary vascular models that represent the systemic circulation, and a three-element Windkessel model to approximate the pulmonary circulation. Using the connection between the systemic arterial pressure and coronary flow regulation systems, and the hybrid closed loop model, we studied how the heart, coronary vascular beds, and arterial system respond to physiologic changes during light exercise and showed that these models can realistically simulate temporal behaviors of the heart, coronary vascular beds, and arterial system during exercise of healthy subjects. These models can be used to study temporal changes occurring in the heart, coronary vascular beds, and arterial system during cardiovascular intervention or changes in physiological states. PMID- 20352336 TI - Shear stress variation induced by red blood cell motion in microvessel. AB - We simulated red blood cells flowing in microvessel to examine the induced wall shear stress variation. A typical peak-valley-peak structure is observed, and it is analyzed in terms of its magnitude, spatial influencing range, and temporal elapsed duration. Effects of red cell deformability, microvessel size, and flow velocity have been investigated. The corresponding variation characters have also been related to cell deformation and flow field. Simulation results show that the variation magnitude is mainly determined by the gap size between cell and vessel wall, while the spatial range of the shear stress variation depends on the cell length as well as the microvessel size. For a certain point on the vessel wall, the shear stress variation lasts a short time at a higher flow velocity, and vice versa. As the cell concentration in the microvessel increases, the shear stress variation structure changes accordingly with the two peaks from two close cells merging together, and eventually only one peak is observed at a hematocrit of 30.72%. However, the effect of hematocrit on the variation magnitude of shear stress is less obvious, and the dynamic nature of shear stress is still significant. This represents the first attempt to study the dynamic shear stress variation on microvessel as red blood cells flow by, and the information obtained in this study could be valuable to relevant research, for example, the mechanotransduction in the endothelia glycocalyx layer. PMID- 20352335 TI - Detection of food intake from swallowing sequences by supervised and unsupervised methods. AB - Studies of food intake and ingestive behavior in free-living conditions most often rely on self-reporting-based methods that can be highly inaccurate. Methods of Monitoring of Ingestive Behavior (MIB) rely on objective measures derived from chewing and swallowing sequences and thus can be used for unbiased study of food intake with free-living conditions. Our previous study demonstrated accurate detection of food intake in simple models relying on observation of both chewing and swallowing. This article investigates methods that achieve comparable accuracy of food intake detection using only the time series of swallows and thus eliminating the need for the chewing sensor. The classification is performed for each individual swallow rather than for previously used time slices and thus will lead to higher accuracy in mass prediction models relying on counts of swallows. Performance of a group model based on a supervised method (SVM) is compared to performance of individual models based on an unsupervised method (K-means) with results indicating better performance of the unsupervised, self-adapting method. Overall, the results demonstrate that highly accurate detection of intake of foods with substantially different physical properties is possible by an unsupervised system that relies on the information provided by the swallowing alone. PMID- 20352337 TI - Transport-reaction model of mural thrombogenesis: comparisons of mathematical model predictions and results from baboon models. AB - Thrombogenesis depends on biochemical reactions affected by blood flow dynamics. While mathematical models of mural thrombogenesis provide a means of understanding how blood flow affects thrombus growth, comparisons to experimental data are needed to validate the models and enable prediction of thrombus growth under diverse conditions. In this paper, we present mathematical models of mural thrombogenesis under flow and validation of the models with experimental data collected from a thrombogenic vascular graft segment. The grafts were placed in exteriorized high-flow arteriovenous (AV) shunts in baboons. Radiolabeled platelet deposition onto the thrombogenic segment, a marker of thrombus size, and plasma thrombin-antithrombin (TAT) concentration downstream of the graft, a marker of local thrombin generation, were monitored over time. The mathematical model of mural thrombogenesis consisted of transport-reaction equations in which platelets and thrombin were explicitly considered. We found that the transport reaction model captured the order of magnitude of TAT sampled levels, while calculated rates of platelet deposition agreed well with radioimaging results. Analysis of experimental and modeling data indicates that, at least during part of thrombus growth progression, thrombin generation is in excess and platelet adhesion rates would be sustained even at lower local thrombin concentrations. PMID- 20352338 TI - Tuning multidomain hemodynamic simulations to match physiological measurements. AB - In recent years, considerable progress has been made in creating more realistic models of the cardiovascular system, often based on patient-specific anatomic data, whereas comparatively little progress has been made on incorporating measured physiological data. We have developed a method to systematically adjust the parameters of three-element windkessel outlet boundary conditions of three dimensional blood flow models such that desired features of pressure and flow waveforms are achieved. This tuning method was formulated as the solution of a nonlinear system of equations and employed a quasi-Newton method that was informed by a reduced-order model. The three-dimensional hemodynamic models were solved using a stabilized finite-element method incorporating deformable vessel walls. The tuning method was applied to an idealized common carotid artery, an idealized iliac arterial bifurcation, and a patient-specific abdominal aorta. The objectives for the abdominal aortic model were values of the maximum and minimum of the pressure waveform, an indicator of the pressure waveform's shape, and the mean, amplitude, and diastolic mean of the flow waveform for an infrarenal measurement plane. The hemodynamic models were automatically generated and tuned by custom software with minimal user input. This approach enables efficient development of cardiovascular models for applications including detailed evaluation of cardiovascular mechanics, simulation-based design of medical devices, and patient-specific treatment planning. PMID- 20352340 TI - Should transcobalamin deficiency be treated aggressively? AB - Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain. PMID- 20352341 TI - Basal ganglia lesions in the early stage of Menkes disease. PMID- 20352343 TI - Characterization of coronary arterial plaque. PMID- 20352342 TI - Real-time three-dimensional transoesophageal echocardiography: a new intraoperative feasible and useful technology in cardiac surgery. AB - A new generation of transoesophageal echocardiographic probes with a novel matrix array technique has been recently introduced, allowing three-dimensional (3D) presentation of cardiac structures in real-time. This new tool may potentially provide fast and complete 3D information about cardiac structures improving spatial orientation and overcoming limitations of offline 3D technologies. The aim of this study was to demonstrate the feasibility and usefulness of real-time 3D transoesophageal echocardiography (TOE) for the intraoperative evaluation of cardiac surgery procedures. One-hundred patients underwent transoesophageal echocardiographic examination during cardiac surgery as a part of their routine clinical practice. In the intraoperative pre- and post-cardiopulmonary bypass periods complete 2D and 3D transoesophageal examinations were performed. Feasibility and duration of examinations, and immediate additional anatomical value of 3D versus 2D-TOE were annotated intraoperatively. Image quality, additional clinical value of 3D- compared to standard 2D-TOE and the accuracy in the description of mitral valve pathology by a surgeon and an echocardiographer were evaluated off-line. No complications related to transoesophageal examination occurred and successful intubation was achieved in all 100 patients. Therefore, 200 examinations were performed and analysed considering the pre- and post cardiopulmonary bypass periods. The mean number of acquisitions per patient was 16 +/- 14, including 3D real-time, zoom, full-volume and colour full volume modalities. The duration of the 3D examination was 16 +/- 10 min and the mean image quality score 2.8 +/- 0.7 (in a scale 1-4). In 36 out of 100 cases (36%) 3D TOE provided additional anatomical information. The surgeon evaluated 3D images easier and more accurately than 2D images (88% vs. 76% in the evaluation of mitral valve scallop). Real-time 3D TOE may be used routinely for the intraoperative evaluation of cardiac surgery. Imaging with this new probe facilitates intraoperative evaluation of several surgical procedures with an additional clinical value in selected cases. PMID- 20352344 TI - AtMYB12 gene: a novel visible marker for wheat transformation. AB - Efficiency of plant transformation is less than optimal for many important species, especially for monocots which are traditionally recalcitrant to transformation, such as wheat. And due to limited number of selectable marker genes, identification or selection of those cells that have integrated DNA into appropriate plant genome and to regenerate fully developed plants from the transformed cells, becomes even more difficult. Some of the widely used marker genes belong to the categories of herbicide or antibiotic resistance genes and flourescent protein genes. As they become an integral part of plant genome along with promoters prokaryotic or eukaryotic origin, there are certain health and environmental concerns about the use of these reporter genes. These marker genes are also inefficient with respect to time and space. In this study we have found a novel visible selection agent AtMYB12, to screen transgenic wheat, with in days after transformation. Transformed coleoptiles as well as cells regenerating from transformed cultured scutella, phenotypically exhibit purple pigmentation, making selection possible in limited and reasonable cost, time and space. PMID- 20352346 TI - VEGF gene polymorphism association with diabetic neuropathy. AB - Vascular factors beside metabolic problems are involved in both etiopathogenesis of diabetic neuropathy, and more remarkably, later in "repair" phase, that governs the net balance between neuro-regenerative/degenerative reactions. Regarding ischemic nature of diabetic neuropathy that highlights necessity of blood vessels re-establishment during tissue healing, VEGF (vascular endothelial growth factor) has been recently the subject of extensive investigations in diabetic neuropathy (DNU). This growth factor possesses angiogenic potentials in addition to the hemodynamic functions. The distribution of VEGF gene polymorphisms at positions -7*C/T, -1001*G/C, -1154*G/A and -2578*C/A were analysed by ARMS-PCR in 248 type 1 diabetic British-Caucasian subjects (81 DNU+, 167 DNU-). We have found that distribution of a VEGF gene polymorphism at promoter region (-7*C/T) was significantly different between diabetic subjects with vs. without neuropathy and the allele (C) conferred susceptibility to DNU (P = 0.02; OR = 1.78, 95% CI 1.0-3.1). The present study indicates that polymorphism of the VEGF gene at position -7*C/T might be implicated in the pathogenesis of diabetic neuropathy as it may harbour some functional/regulatory potential in VEGF gene expression. However, this requires further studies in order to better understand its phenotypic impact and to investigate the prognostic value of this polymorphism in diabetic neuropathy as a chronic complication of diabetes. PMID- 20352345 TI - Induction of cytotoxicity by photoexcitation of TiO2 can prolong survival in glioma-bearing mice. AB - We have investigated the possibility that photoexcited titanium dioxide (TiO2) could inhibit the growth of malignant cells. We studied the anti-glioma effects of nano-TiO2 excited with ultraviolet A (UVA) irradiation both in vitro and in vivo. Transmission electron microscopy demonstrated that glioma cells take up TiO2 by phagocytosis, and vital staining revealed that TiO2 alone has no effect on glioma cell proliferation. However, if TiO2 was combined with UVA irradiation the proliferation rate was decreased significantly compared to controls (P<0.05). RT-PCR suggested that TiO2 induction of glioma cell apoptosis is associated with changes in the expression of genes encoding Bcl-2 family members. We then investigated the in vivo antitumor effects of combined TiO2 plus UVA treatment of established glioma tumors. TiO2 plus UVA led to pronounced areas of necrosis, elevated indices of apoptosis, delayed tumor growth, and increased survival compared with the TiO2-alone control group (P<0.001). Log-rank survival analysis showed that median survival duration was prolonged (P<0.001). These findings suggest that nano-TiO2 based photodynamic therapy has potential in the treatment of glioma. PMID- 20352347 TI - Complete mitochondrial genome of the Chinese spiny lobster Panulirus stimpsoni (Crustacea: Decapoda): genome characterization and phylogenetic considerations. AB - The genetics and molecular biology of the commercially important Chinese spiny lobster, Panulirus stimpsoni are little known. Here, we present the complete mitochondrial genome sequence of P. stimpsoni, determined by the long polymerase chain reaction and primer walking sequencing method. The entire genome is 15,677 bp in length, encoding the standard set of 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. The overall A+T content of the genome is 65.6%, lower than most malacostracan species. The gene order is consistent with the pancrustacean ground pattern. Several conserved elements were identified from P. stimpsoni control region, viz. one [TA(A)]n-block, two GA-blocks and three hairpin structures. However, the position of [TA(A)]n-block and number of hairpin structure are different from those in the congeneric P. japonicus and other decapods. Phylogenetic analyses using the concatenated nucleotide and amino acid sequences of 13 protein-coding genes do not support the monophyly of suborder Pleocyemata, which is in contrast to most morphological and molecular results. However, the position of Palinura and Astacidea is unstable, as represented by the basal or sister branches to other Reptantia species. P. stimpsoni, as the second species of Palinura with complete mitochondrial genome available, will provide important information on both genomics and conservation biology of the group. PMID- 20352349 TI - Polymorphism of DLK1 and CLPG gene and their association with phenotypic traits in Chinese cattle. AB - DLK1 and CLPG were located in DLK1-GTL2 imprinted cluster. They all affected muscle growth and meat tenderness. The functional importance of DLK1 and CLPG imply that the variation of the genes could affect the growth traits of animal. PCR-SSCP and sequencing were used to analyze the four loci of DLK1 gene and CLPG gene in 1109 individuals, which belong to eight breeds/species of bovidae, including cattle, buffalo and yak. A synonymous mutation (C451T) was detected in exon 5 of DLK1 in Qinchuan cattle, but didn't change significantly with phenotypic traits. Three genotypes AA, AB and AC of CLPG were identified in Jiaxian cattle. The associations analyst of different genotypes showed that the individuals with genotypes AA and AC had a greater body weight and longer body length than those with genotype AB (P<0.05 and P<0.01, respectively); the AA individuals were different from those AB (P<0.05) in the circumference of cannon bone. No polymorphism was observed in the other populations at other loci. These results were in agreement with the homology analysis: DLK1 and CLPG genes were in a highly conserved. PMID- 20352348 TI - Protective effect of Spirulina against 4-nitroquinoline-1-oxide induced toxicity. AB - In the present study, we focused on the protective effect of Spirulina against 4 nitroquinoline-1-oxide (4NQO) induced hepato and nephrotoxicity in the experimental rats. The 4NQO administration resulted in increased levels of hepatic and renal markers [Alanine Transaminase (ALT), Aspartate Transaminase (AST), Lactate Dehydrogenase (LDH), urea, creatinine and uric acid] in the serum of experimental animals. It also increased the oxidative stress resulting in increased levels of the lipid peroxidation with a concomitant decline in the levels of non enzymic [reduced glutathione (GSH)] and enzymic antioxidants [(Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and Glutathione-S-transferase (GST)] in both liver and kidney. Oral pretreatment with aqueous extract of Spirulina prevented 4NQO induced changes in the levels of hepatic and kidney diagnostic marker enzymes in the serum of experimental rats. It counteracted the 4NQO induced lipid peroxidation and maintained the hepatic and kidney antioxidant defense system at near normal in both liver and kidney. The antioxidant responsiveness mediated by Spirulina may be anticipated to have biological significance in eliminating reactive free radicals that may otherwise affect normal cell functioning and provide a scientific rationale for the use of Spirulina. PMID- 20352355 TI - Economic dependence and unprotected sex: the role of sexual assertiveness among young urban mothers. AB - In the USA, sexual intercourse is the leading route of human immunodeficiency virus transmission among women, primarily through their main partner. Because male condom use is not directly under a woman's control, gender inequalities may help shape this sexual risk behavior. To examine this association, data came from follow-up interviews of young, primarily minority, pregnant women enrolled in a prospective, randomized controlled trial. Specifically, we aimed to determine the relationship between economic dependence on a male partner and condom use, and to establish whether this relationship was mediated by sexual assertiveness. Overall, 28% of women reported being economically dependent on a male partner. Young women dependent on a male partner were 1.6 times more likely to report not using a condom at last sex than women not dependent on their partner (95% confidence interval = 1.11-2.32; p = 0.01). Sexual assertiveness mediated the relationship between economic dependence and condom use (Sobel = 2.05, p = 0.04). Coupled with past research, this study supports the premise that sexual behaviors may be rooted in a complex web of social determinants. Addressing gender inequalities in contextual factors may promote healthier decisions within sexual relationships. PMID- 20352350 TI - White matter: organization and functional relevance. AB - Norman Geschwind's landmark paper in 1965, "Disconnexion Syndromes in Animals and Man," inspired a generation of investigators to consider the effects of focal brain lesions disrupting higher brain functions. Although Geschwind viewed disconnection as resulting from either white or gray matter lesions, his signature article drew upon the insights of 19th century neurologists and firmly established white matter within the vocabulary of behavioral neurology, neuropsychology, and cognitive neuroscience. This influence, and the advent of sensitive neuroimaging techniques later in the 20th century, led to white matter gradually gaining more attention as an essential component of distributed neural networks subserving cognition and emotion. Today, whereas focal white matter lesions remain central to the pathogenesis of classic neurobehavioral syndromes, diffuse white matter involvement is regarded as increasingly relevant to a wide variety of dementia syndromes and a host of neuropsychiatric disorders as well. In parallel, better understanding of the neurobiology of brain white matter at all ages has been achieved. While much remains to be explored, a general conceptual formulation is that white matter supports information transfer to complement the information processing carried out by gray matter. As knowledge of the organization and functional relevance of white matter continues to advance, improved understanding of the role of myelinated tracts in higher function can be anticipated, and with it many clinical benefits. PMID- 20352352 TI - Ice phase as an important factor on the seasonal variation of polycyclic aromatic hydrocarbons in the Tumen River, Northeastern of China. AB - BACKGROUND, AIM AND SCOPE: The climatic characteristic is a major parameter affecting on the distribution variation of organic pollutants such as polycyclic aromatic hydrocarbons (PAHs). The Tumen River is located in Northeastern of China. The winter era lasts for more than 5 months in a year, and the river water was frozen and covered by ice phase. Coal combustion is an essential heating source in the Tumen River Basin. The objective of this research is to study ice phase effect on the seasonal variation of PAHs in the Tumen River environment. MATERIALS AND METHODS: Samples were collected from 13 sites along the River in March, July, October, and December of 2008. In addition, the ice sample, under ice water and air particulate were also collected in winter. The samples were analyzed for 16 PAHs (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, beazo[a]anthene, chrysene, beazo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno(1,2,3 cd)pyrene, dibenz(a,h)anthracene, and benzo(ghi)perylene). The compounds were extracted from the water samples and solid samples using LLE and Soxhlet extraction technique, respectively, and it is determined by gas chromatography mass spectrometry. RESULTS AND DISCUSSION: Among 16 PAHs, fluorene, phenanthrene, and pyrene were found to be present in high concentrations and at high detection frequencies. The total concentration of PAHs in the water, particulate, sediment and ice phase ranged from 35.1-1.05 x 10(3) ng L(-1), 25.4-817 ng L(-1), 117-562 ng g(-1)and 62.8-136 ng g(-1), respectively. The levels of PAHs were generally higher in spring than other seasons. The ice phase in winter acts like a major reservoir of the pollutants and it is major contributor on the seasonal variation of PAHs in Tumen River. The PAHs found in water, particulate, and sediment in the Tumen River were possibly derived from similar pollution sources a proposition based on the compositions and isomer ratios of PAHs. CONCLUSIONS: The distribution of PAHs was showed clear seasonal variation in the Tumen River environment, the ice phase and air pollution look like an important factor affecting on the seasonal variation. RECOMMENDATIONS AND PERSPECTIVES: The ice phase as an important factor affecting on the seasonal variation of PAHs in Tumen River environment. Further studies regarding the effects of air pollution on the river and the mechanisms of migration and transformation of them in the environment are currently being conducted in our laboratory. PMID- 20352356 TI - Primary and secondary analysis of local elected officials' decisions to support or oppose pharmacy sale of syringes in California. AB - Under California law, local governments may authorize pharmacies within their jurisdictions to sell ten or fewer syringes to an adult without prescription, proof of identity, or proof of medical need. Local governments may simultaneously exempt adults from prosecution for violation of state drug paraphernalia codes for possession of ten or fewer syringes for personal use. Both of these provisions are temporary and sunset on December 31, 2010, unless subsequent state legislation amends that date. The objective of our study was to ascertain how and why local policymakers made their decisions regarding non-prescription syringe sale (NPSS). We examined influences on their decisions, including specific messengers and the arguments that were most salient to their decision making. We selected jurisdictions that were geographically representative of California counties; those with and without syringe exchange programs, and those that had passed or rejected NPSS. We conducted nine semi-structured interviews in five jurisdictions. To enrich primary data collection, we analyzed secondary data by reviewing audio, video, and written transcripts of public hearings and newspaper coverage in five jurisdictions, including three jurisdictions without primary interview data. Among proponents of NPSS, we identified common themes, including: (1) public health research provided conclusive evidence for reduction in HIV and hepatitis transmission without problems of crime, drug use, or unsafe discard of syringes; (2) the local health officer was the key to influencing local policymakers; (3) recall of prior debates over syringe exchange served to inform their decision making; and (4) a lack of local opposition or controversy. Common concerns among opponents of NPSS included: (1) that there would be an increase in unsafe discard of syringes; (2) loss of an important law enforcement tool; (3) that drug users were incapable of desired behavior change; and (4) that research was inconclusive, or proved that syringe access would not work in reducing rates of disease. Themes held in common by proponents and opponents of NPSS were identified as well. Syringe access through NPSS is in fact supported by a robust body of public health research and is considered an important component of a comprehensive strategy to reduce HIV and hepatitis transmission. Our study highlights the importance of understanding the perspectives of elected officials in order to ameliorate their concerns without undermining the public health goal of reducing death, disease, and suffering in at-risk communities. PMID- 20352357 TI - Microwave ablation therapy for treating primary and secondary lung tumours: technical note. AB - PURPOSE: The purpose of our study was to retrospectively evaluate the feasibility, safety and effectiveness of microwave ablation (MWA) in nine patients with unresectable lung tumour. MATERIALS AND METHODS: Ten lesions were treated in ten ablation sessions in nine patients. The treatments were performed with a microwave generator with 45 W and 915 MHz connected to a 14.5-gauge antenna for 10 min. Antenna placement was performed with computed tomography (CT) fluoroscopy guidance or XperGuide. All patients underwent CT follow-up at 1, 3 and 6 months from the procedure. RESULTS: Technical success was obtained in all cases; mortality at 30 days was 0%. CONCLUSIONS: This study shows that in selected patients, MWA is a valid alternative to other ablative techniques. Further studies are required to demonstrate the short- and long-term effects of this technique and to make a comparison with other available ablation systems, especially with radiofrequency. PMID- 20352358 TI - Ultrasound transmission gel as a bolus device for skin irradiation of irregular surfaces: technical note. AB - PURPOSE: This paper describes an uncommon radiation treatment of the external ear, with ultrasound (US) transmission gel used as bolus device to compensate for the irregularity of the target surface. MATERIALS AND METHODS: Postoperative radiotherapy for cutaneous carcinoma was performed with a single high-energy electron beam directed over the ear auricle. Due to the irregular surface of the target, a "missing tissue" compensator was employed. Daily, after patient positioning, the concha was filled and flattened with US gel, and a dose of 54 Gy in 27 fractions was delivered. RESULTS: Water equivalence of the gel was verified by comparing the gel's computed tomography (CT) number [Hounsfield units (HU)] and density with the corresponding values for water and another commercial bolus device. Whereas ultrasound gel and water had comparable values (HU: 0; density 1 g/cm(3) for both), the corresponding values for the commercial device were slightly higher (HU: 80; density 1.02 g/cm(3)). CONCLUSIONS: Ultrasound gel proved to be an easy, fast and cheap compensating tool. Its water equivalence allows it to be used as an alternative to water, though easier to position and with lower risk of displacement. Thus, it is recommendable as a practical tool for most irregular sites. Further investigations are warranted to validate this solution in more complex irradiation techniques. PMID- 20352359 TI - The effect of the lipid-binding site of the ankyrin-binding domain of erythroid beta-spectrin on the properties of natural membranes and skeletal structures. AB - It was previously shown that the beta-spectrin ankyrin-binding domain binds lipid domains rich in PE in an ankyrin-dependent manner, and that its N-terminal sequence is crucial in interactions with phospholipids. In this study, the effect of the full-length ankyrin-binding domain of beta-spectrin on natural erythrocyte and HeLa cell membranes was tested. It was found that, when encapsulated in resealed erythrocyte ghosts, the protein representing the full-length ankyrin binding domain strongly affected the shape and barrier properties of the erythrocyte membrane, and induced partial spectrin release from the membrane, while truncated mutants had no effect. As found previously (Bok et al. Cell Biol. Int. 31 (2007) 1482-94), overexpression of the full-length GFP-tagged ankyrin binding domain aggregated and induced aggregation of endogenous spectrin, but this was not the case with overexpression of proteins truncated at their N terminus. Here, we show that the aggregation of spectrin was accompanied by the aggregation of integral membrane proteins that are known to be connected to spectrin via ankyrin, i.e. Na(+)K(+)ATP-ase, IP3 receptor protein and L1 CAM. By contrast, the morphology of the actin cytoskeleton remained unchanged and aggregation of cadherin E or N did not occur upon the overexpression of either full-length or truncated ankyrin-binding domain proteins. The obtained results indicate a substantial role of the lipid-binding part of the beta-spectrin ankyrin-binding domain in the determination of the membrane and spectrin-based skeleton functional properties. PMID- 20352360 TI - More thoughts: on the spirit of community psychology. PMID- 20352361 TI - Investing in success: key strategies for building quality in after-school programs. AB - This paper examines the relation between the implementation quality of after school literacy activities and student reading gains. The data are from an evaluation of a multi-site after-school program in California in which continuous program quality improvement strategies were implemented to improve the delivery of a new balanced literacy program. Strategies included: (1) targeted staff training throughout the year, (2) regular observations and coaching of staff, and (3) the use of data to measure progress. Programs struggled to successfully implement these strategies early in the initiative, but gradually improved the quality and consistency of their use. Program quality, as measured through observations, also increased. Results suggested that the size of student reading gains were positively correlated with the quality of literacy programming provided by each instructor. PMID- 20352362 TI - Impact of diabetes on postoperative outcomes following colon cancer surgery. AB - BACKGROUND: Diabetes is the sixth most common cause of death in the US and causes significant postoperative mortality and morbidity. OBJECTIVE: To characterize the impact of diabetes among patients undergoing surgery for colorectal cancer. DESIGN: This is is a retrospective cohort study. PARTICIPANTS: Patients in the Nationwide Inpatient Sample (NIS) who had undergone colorectal cancer surgery between 1998 and 2005. MEASUREMENTS: Using multivariate regression, we determined the association of diabetes status with postoperative mortality, postoperative complications, and length of stay. KEY RESULTS: An estimated 218,534 patients had undergone surgery for colorectal cancer. We categorized subjects by the presence of diabetes, the prevalence of which was 15%. Crude postoperative in-hospital mortality was lower among diabetics compared to non-diabetics (2.5% vs. 3.2%, P < 0.0001). Adjusted mortality was 23% lower in those with diabetes compared to non diabetics (aOR 0.77; 95% CI: 0.71-0.84). Diabetics also had lower adjusted post operative complications compared to non-diabetics (aOR 0.82; 95% CI: 0.79-0.84). In uninsured individuals and patients <50 years of age, there was no protective association between diabetes and either in-hospital mortality or postoperative complications. CONCLUSIONS: In patients undergoing colorectal cancer surgery, those with diabetes had a 23% lower mortality and fewer postoperative complications compared to non-diabetics. The mechanisms underlying this unexpected observation warrant further investigation. PMID- 20352363 TI - A qualitative study of the meaning of physical examination teaching for patients. AB - BACKGROUND: Physical examination teaching using actual patients is an important part of medical training. The patient experience undergoing this type of teaching is not well-understood. OBJECTIVE: To understand the meaning of physical examination teaching for patients. DESIGN: Phenomenological qualitative study using semi-structured interviews. PARTICIPANTS: Patients who underwent a physical examination-based teaching session at an urban Veterans Affairs Medical Center. APPROACH: A purposive sampling strategy was used to include a diversity of patient teaching experiences. Multiple interviewers triangulated data collection. Interviews continued until new themes were no longer heard (total of 12 interviews). Interviews were recorded and transcribed verbatim. Coding was performed by two investigators and peer-checked. Themes were identified and meanings extracted from themes. KEY RESULTS: Seven themes emerged from the data: positive impression of students; participation considered part of the program; expect students to do their job: hands-on learning; interaction with students is positive; some aspects of encounter unexpected; range of benefits to participation; improve convenience and interaction. Physical examination teaching had four possible meanings for patients: Tolerance, Helping, Social, and Learning. We found it possible for a patient to move from one meaning to another, based on the teaching session experience. CONCLUSIONS: Physical examination teaching can benefit patients. Patients have the potential to gain more value from the experience based on the group interaction. PMID- 20352364 TI - Diagnosis and management of mineral metabolism in CKD. AB - BACKGROUND: Chronic kidney disease (CKD) affects over 26 million Americans and is frequently complicated early in its course by disordered mineral metabolism and metabolic bone disease. Since CKD-related bone loss is often indistinguishable from osteoporosis by standard bone densitometry, many CKD patients may be inappropriately treated with bisphosphonates rather than CKD-specific therapies. OBJECTIVE: To determine the prevalence of appropriate evaluation, diagnosis and management of metabolic bone disease among individuals with pre-dialysis CKD. DESIGN AND PARTICIPANTS: Retrospective cohort study using electronic medical records of 69,215 ambulatory patients seen in the primary care clinics of an academic medical center. MEASUREMENTS: Prevalence of CKD stages 3-4, frequency of diagnostic testing and treatment of metabolic bone disease. MAIN RESULTS: Based on current diagnostic criteria and consistent with national data, CKD was present in 12% of the population. Bisphosphonates were used in 7.2% of patients, 20% of whom met criteria for CKD. Fewer than half of CKD patients underwent testing for parathyroid hormone (PTH) or 25-hydroxyvitamin D (25D) levels. Among those tested, vitamin D deficiency (25D <30 ng/ml) and secondary hyperparathyroidism (PTH >60 pg/ml) were present in 65% and 55%, respectively. Among patients with CKD, bisphosphonate use was nearly seven times as frequent as therapy with active vitamin D (12% vs. 1.7%, p < 0.0001), a primary treatment for CKD-associated metabolic bone disease. CONCLUSIONS: Disordered mineral metabolism in CKD is common, under-diagnosed and under-treated. As a result, bisphosphonates may be prescribed inappropriately in patients with CKD. PMID- 20352366 TI - Venous thromboembolism prophylaxis among medical patients at US hospitals. AB - BACKGROUND: Chemoprophylaxis is recommended for medical patients at moderate to high risk of venous thromboembolism (VTE) and is now a requirement of the Joint Commission on Accreditation of Healthcare Organizations. To see who receives prophylaxis and how far hospitals will need to go to meet this requirement, we examined VTE prophylaxis patterns at US hospitals. METHODS: We conducted a retrospective cohort study of adult patients with seven medical diagnoses considered to carry moderate to high risk of VTE at 376 acute care facilities in 2004-2005. We excluded patients on warfarin or with hospital stays of <2 days. VTE prophylaxis was assessed by billing codes for any heparin or compression device. We classified patient risk using a VTE risk prediction model. RESULTS: Of 351,535 patients included, 36% received prophylaxis by hospital day 2. Prophylaxis rates were highest among patients with certain VTE risk factors, including mechanical ventilation (67%), restraints (57%), central lines (55%), obesity (46%), and prior VTE (44%). The median hospital rate was 31% (IQR 19% to 42%); only 3% of hospitals had rates >70%. Compared to patients at low risk of VTE (<0.05%), patients at high risk (>1.0%) were more likely to receive prophylaxis (52% vs. 34%, p < 0.001). Hospitals with high rates of prescribing for high-risk patients also had high rates for low-risk patients. CONCLUSIONS: VTE prophylaxis rates at US hospitals are substantially below Joint Commission targets, even for patients at highest risk of VTE. PMID- 20352367 TI - U.S. trends in hospitalization and generalist physician workforce and the emergence of hospitalists. AB - BACKGROUND: General internists and other generalist physicians have traditionally cared for their patients during both ambulatory visits and hospitalizations. It has been suggested that the expansion of hospitalists since the mid-1990s has "crowded out" generalists from inpatient care. However, it is also possible that declining hospital utilization relative to the size of the generalist workforce reduced the incentives for generalists to continue providing hospital care. OBJECTIVE: To examine trends in hospital utilization and the generalist workforce before and after the emergence of hospitalists in the U.S. and to investigate factors contributing to these trends. DESIGN: Using data from 1980-2005 on inpatient visits from the National Hospital Discharge Survey, and physician manpower data from the American Medical Association, we identified national trends before and after the emergence of hospitalists in the annual number of inpatient encounters relative to the number of generalists. RESULTS: Inpatient encounters relative to the number of generalists declined steadily before the emergence of hospitalists. Declines in inpatient encounters relative to the number of generalists were driven primarily by reduced hospital length of stay and increased numbers of generalists. CONCLUSIONS: Hospital utilization relative to generalist workforce declined before the emergence of hospitalists, largely due to declining length of stay and rising generalist workforce. This likely weakened generalist incentives to provide hospital care. Models of care that seek to preserve dual-setting generalist care spanning ambulatory and inpatient settings are most likely to be viable if they focus on patients at high risk of hospitalization. PMID- 20352368 TI - The incidence and risk factors of post-laparotomy adhesive small bowel obstruction. AB - INTRODUCTION: The purpose of this review was to assess the incidence and risk factors for adhesive small bowel obstruction (SBO) following laparotomy. METHODS: The PubMed database was systematically reviewed to identify studies in the English literature delineating the incidence of adhesive SBO and reporting risk factors for the development of this morbidity. RESULTS: A total of 446,331 abdominal operations were eligible for inclusion in this analysis. The overall incidence of SBO was 4.6%. The risk of SBO was highly influenced by the type of procedure, with ileal pouch-anal anastomosis being associated with the highest incidence of SBO (1,018 out of 5,268 cases or 19.3%), followed by open colectomy (11,491 out of 121,085 cases or 9.5%). Gynecological procedures were associated with an overall incidence of 11.1% (4,297 out of 38,751 cases) and ranged from 23.9% in open adnexal surgery, to 0.1% after cesarean section. The technique of the procedure (open vs. laparoscopic) also played a major role in the development of adhesive SBO. The incidence was 7.1% in open cholecystectomies vs. 0.2% in laparoscopic; 15.6% in open total abdominal hysterectomies vs. 0.0% in laparoscopic; and 23.9% in open adnexal operations vs. 0.0% in laparoscopic. There was no difference in SBO following laparoscopic or open appendectomies (1.4% vs. 1.3%). Separate closure of the peritoneum, spillage and retention of gallstones during cholecystectomy, and the use of starched gloves all increase the risk for adhesion formation. There is not enough evidence regarding the role of age, gender, and presence of cancer in adhesion formation. CONCLUSION: Adhesion-related morbidity comprises a significant burden on healthcare resources and prevention is of major importance, especially in high-risk patients. Preventive techniques and special barriers should be considered in high-risk cases. PMID- 20352369 TI - Modeling the relationship between cervical cancer mortality and trace elements based on genetic algorithm-partial least squares and support vector machines. AB - The relationship between the mortality of cervical cancer and soil trace elements of 23 regions of China was investigated. A total of 25 elements (i.e., Na, K, Mg, Ca, Sr, Hg, Pb, B, Tm, Th, U, Sn, Hf, Bi, Ta, Te, Mo, Br, I, As, Cr, Cu, Fe, Zn, and Se) were considered. First, 23 samples were split into the training set with 12 samples and the test set with 11 samples. Then, a combination strategy called genetic algorithm-partial least squares (GA-PLS) was used to pick out five important elements. i.e., Br, Ta, Pb, Cr, and As. Afterwards, the classic partial least squares (PLS) model and least square support vector machine (LSSVM) model were developed and compared. The results revealed that the SVM model significantly outperforms the PLS model, indicating that the combination of GA PLS and LSSVM can serve as a potential tool for predicting the mortality of cancer based on trace elements. PMID- 20352370 TI - Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. AB - This study was performed to assess how 4 weeks of magnesium supplementation and exercise affect the free and total plasma testosterone levels of sportsmen practicing tae kwon do and sedentary controls at rest and after exhaustion. The testosterone levels were determined at four different periods: resting before supplementation, exhaustion before supplementation, resting after supplementation, and exhaustion after supplementation in three study groups, which are as follows: Group 1-sedentary controls supplemented with 10 mg magnesium per kilogram body weight. Group 2-tae kwon do athletes practicing 90 120 min/day supplemented with 10 mg magnesium per kilogram body weight. Group 3 tae kwon do athletes practicing 90-120 min/day receiving no magnesium supplements. The free plasma testosterone levels increased at exhaustion before and after supplementation compared to resting levels. Exercise also increased testosterone levels relative to sedentary subjects. Similar increases were observed for total testosterone. Our results show that supplementation with magnesium increases free and total testosterone values in sedentary and in athletes. The increases are higher in those who exercise than in sedentary individuals. PMID- 20352371 TI - The effects of FeCl3 and Fe-EDTA on the development of psoriasis. AB - The effects of FeCl3 and Fe-EDTA on the development of psoriasis were studied in the mouse model of vaginal epithelium and tail epidermis. The mitoses of vaginal epithelial cell in female mice of their estrogenic stage and the formation of granular cell layers in male mouse tail scale were observed. Mice were randomly divided into eight groups and treated with normal saline, methotrexate, and different doses of two iron forms, FeCl3 and Fe-EDTA, respectively, for 10 days. To explore the influence of FeCl3 and Fe-EDTA on the excretion of Cu, Fe, Zn, Ca, Mg, Mn, and Se, the concentration of those elements in liver and kidney was analyzed by atomic absorption spectrometry. The different doses of FeCl3 or Fe EDTA could obviously inhibit the mitoses of vaginal epithelial cell (p< 0.05) and promote the formation of granular cell layers in mice tail scale (p < 0.05). No statistically significant results were found between the groups of FeCl3 and Fe EDTA, and between experimental groups and methotrexate group acted as the positive control (p>0.05). Compared with the negative group, the concentrations of Cu, Fe, Zn, Ca, Mg, Mn, and Se in liver and kidney of experimental groups and positive control group were not significantly changed (p > 0.05). FeCl3 and Fe EDTA are as effective as methotrexate on inhibiting hyperplasia of epidermal cells and increasing the formation of granular cell layers, and the concentrations of Cu, Fe, Zn, Ca, Mg, Mn, and Se in liver and kidney of experimental groups and positive control group were not significantly changed compared with the negative group, possibly retarding the development of psoriasis. PMID- 20352372 TI - Effects of 17beta-estradiol and vitamin E treatments on blood trace element and antioxidant enzyme levels in ovariectomized rats. AB - We investigated the effect of 17beta-estradiol (E(2)) alone and separately vitamin E treatment on trace element status of rats following an ovariectomic operation. Forty rats were equally divided into four groups: Group 1, control, non-ovariectomized rats; Group 2, (OVX) rats, ovariectomized under general anesthesia; Group 3, (OVX+E(2)) rats, the group received a 40 ug kg(-1) subcutan dose of E(2) per day after ovariectomy; and Group 4, (OVX + E(2) + vitamin E) rats, received the same E(2) treatment, but with an additional 100 mg kg(-1) intraperitoneal dose of vitamin E per day after ovariectomy. At the end of the 30 day experiment, the rats were sacrificed and their blood was collected for the measurement of zinc, copper, iron, phosphorus, selenium, magnesium, calcium, manganese, and chromium; copper-zinc superoxide dismutase (SOD); manganese superoxide dismutase (Mn-SOD); glutathione peroxidase (Se-GSH-Px); and catalase (CAT). The levels of zinc, copper, iron, phosphorus, selenium, calcium, chromium, and manganese and activities of SOD, Mn-SOD, Se-GSH-Px, and CAT were lower in the OVX than in the control group, but magnesium level was unaffected. However, zinc, copper, iron, phosphorus, selenium, calcium, chromium, and manganese levels and SOD, Mn-SOD, Se-GSH-Px, and CAT activities were higher under separate E(2) and E(2) + vitamin E treatments. The level of magnesium in the treated-OVX groups was not different than in the OVX group. In conclusion, E(2) treatment has an ameliorating effect on the trace element status in OVX, and this effect may be enhanced with the addition of vitamin E. PMID- 20352373 TI - Amiloride reduces sodium transport and accumulation in the succulent xerophyte Zygophyllum xanthoxylum under salt conditions. AB - To investigate the effects of amiloride, which is an inhibitor of Na(+)/H(+) antiporter (NHX), on Na(+) accumulation and transport at the whole plant level, in this study, 3-week-old Zygophyllum xanthoxylum plants were exposed to 25, 50 and 100 mM NaCl with or without 0.5 mM amiloride. After 72 h of treatment, dry weight, tissue water content, Na(+) and K(+) concentrations, and transcript levels of ZxNHX were determined. The results indicated that, under salt conditions, leaf Na(+) concentration, total Na(+) quantity and root net Na(+) uptake rate in plants treated with amiloride are significantly lower than those in control plants. Amiloride remarkably increased Na(+) proportion in stem and decreased Na(+) proportion in leaf of Z. xanthoxylum. Furthermore, our results showed that the transcript levels of ZxNHX are down-regulated by amiloride. It is clear that the inhibition of vacuolar Na(+)/H(+) antiporter by amiloride could disrupt Na(+) accumulation of leaf, and reduce Na(+) uptake by root and Na(+) transport from stem to leaf, thus resulting in the growth inhibition of Z. xanthoxylum exposed to salt. PMID- 20352374 TI - Digitalis does not improve left atrial mechanical dysfunction after successful electrical cardioversion of chronic atrial fibrillation. AB - This study was designed to investigate whether administration of digitalis could improve mechanical function of left atrial appendage (LAA) and left atrium prospectively in patients with atrial stunning. Fifty-four consecutive patients in whom atrial stunning was observed immediately after cardioversion of chronic atrial fibrillation (AF) were randomized into digitalis or control group for 1 week following cardioversion. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed prior to, immediately following, 1 day after and 1 week after cardioversion to measure transmitral flow velocity and LAA flow velocity. Electrical cardioversion of AF elicited significantly slower left atrial appendage peak emptying velocity (LAA-PEV) and peak filling velocity (LAA-PFV) immediately following cardioversion in both groups. 1 day post cardioversion, there were no significant differences in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or left atrial appendage ejection fraction (LAA-EF) between digitalis and control groups. 1 week post cardioversion, no significant differences were found in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or LAA-EF between the two groups. The occurrence rates of spontaneous echo contrast were not significantly different between digitalis and control groups one day and one week post cardioversion. In conclusion, digitalis did not improve left atrial and appendage mechanical dysfunction following cardioversion of chronic AF. Digitalis did not prevent the development of spontaneous echo contrast in left atrial chamber and appendage. This may be due to the fact that digitalis aggravates intracellular calcium overload induced by chronic AF and has a negative effect on ventricular rate. PMID- 20352375 TI - The effects of copper (II) ions on Enterococcus hirae cell growth and the proton translocating FoF1 ATPase activity. AB - Enterococcus hirae grow well under anaerobic conditions at alkaline pH (pH 8.0) producing acids by glucose fermentation. Bacterial growth was shown to be accompanied by decrease of redox potential from positive values (approximately +35 mV) to negative ones (approximately -220 mV). An oxidizer copper (II) ions (Cu(2+)) affected bacterial growth in a concentration-dependent manner (within the range of 0.05 mM to 1 mM) increasing lag phase duration and decreasing specific growth rate. These effects were observed with the wild-type strain ATCC9790 and the atpD mutant strain MS116 (with absent beta subunit of F(1) of the F(o)F(1) ATPase) both. Also ATPase activity and proton-potassium ions exchange were assessed with and without N,N'-dicyclohexylcarbodiimide (DCCD), inhibitor of the F(o)F(1) ATPase. In both cases (DCCD +/-), even low Cu(2+) concentrations had noticeable effect on ATPase activity, but with less visible concentration-dependent manner. Changes in the number of accessible SH-groups were observed with E. hirae ATCC9790 and MS116 membrane vesicles. In both strains Cu(2+) markedly decreased the number of SH-groups in the presence of K(+) ions. The addition of ATP increased the amount of accessible SH-groups in ATCC9790 and decreased this number in MS116; Cu(2+) blocked ATP-installed increase in SH groups number in ATCC9790. H(+)-K(+)-exchange of bacteria was markedly inhibited by Cu(2+), but stronger effects were detected together with DCCD. Moreover, discrimination between Cu(2+) and other bivalent cation--Ni(2+) was shown. It is suggested that Cu(2+) ions inhibit E. hirae cell growth by direct affect on the F(o)F(1) ATPase leading to conformational changes in this protein complex and decrease in its activity. PMID- 20352376 TI - Production and stability of protease from Candida buinensis. AB - Cow raw milk from dairy cooperatives was examined for its microbial composition. Among the isolates identified, 17.6% were yeasts. The most frequent genus was Candida, although members belonging to the genera Brettanomyces, Dekkera, and Geotricum were also identified. Although qualitative and quantitative tests for extracellular proteolytic activity were positive for all the species isolated, Candida buinensis showed the highest response (23.5 U/mg); therefore, it was selected for subsequent investigation. The results of fermentations carried out at variable temperature, pH, and soybean flour concentration, according to a 2(3) full factorial design, demonstrated that this yeast ensured the highest production of extracellular proteases (573 U/mL) when cultivated at 35 degrees C, pH 6.5, and using soybean flour concentrations in the range 0.1-0.5% (w/v). The cell-free supernatants showed the highest activity at 25 degrees C and pH 7.0, and satisfactory stability in the ranges 25-30 degrees C and pH 7-9. The first order rate constants of protease inactivation in the cell-free supernatants were calculated at different temperatures from semi-log plots of the residual activity versus time and then used in Arrhenius and Eyring plots to estimate the main thermodynamic parameters of thermoinactivation (E* = 40.0 kJ/mol; DeltaH* = 37.3 kJ/mol; DeltaS* = -197.5 J/mol K; DeltaG* = 101 kJ/mol). PMID- 20352377 TI - An uncommon clinical picture: Wellens' syndrome in a morbidly obese young man. PMID- 20352378 TI - Spelling deficits in dyslexia: evaluation of an orthographic spelling training. AB - Orthographic spelling is a major difficulty in German-speaking children with dyslexia. The aim of the present study was to evaluate the effectiveness of an orthographic spelling training in spelling-disabled students (grade 5 and 6). In study 1, ten children (treatment group) received 15 individually administered weekly intervention sessions (60 min each). A control group (n = 4) did not receive any intervention. In study 2, orthographic spelling training was provided to a larger sample consisting of a treatment group (n = 13) and a delayed treatment control group (n = 14). The main criterion of spelling improvement was analyzed using an integrated dataset from both studies. Repeated-measures analysis of variance revealed that gains in spelling were significantly greater in the treatment group than in the control group. Statistical analyses also showed significant improvements in reading (study 1) and in a measure of participants' knowledge of orthographic spelling rules (study 2). The findings indicate that an orthographic spelling training enhances reading and spelling ability as well as orthographic knowledge in spelling-disabled children learning to spell a transparent language like German. PMID- 20352379 TI - NUT gene rearrangement in a poorly-differentiated carcinoma of the submandibular gland. AB - NUT midline carcinomas (NMC) are a rare, recently described class of poorly differentiated tumors that exhibit rapid onset and highly aggressive clinicopathologic behavior. These tumors are defined by rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, most commonly in a balanced translocation with the BRD4 gene on chromosome 19p13.1, resulting in the characteristic BRD4-NUT fusion gene and protein which blocks epithelial differentiation through chromatin binding. NMC frequently involve midline structures of adolescents and young adults and affect the head and neck region in 50% of cases. To our knowledge, only one case has been previously reported involving a salivary gland. Here, we present a case of a NMC of the salivary gland in an adolescent male presenting with an intermittently painful left submandibular mass of 3 months duration. PMID- 20352380 TI - Successful treatment of Aspergillus liver abscesses in a patient with acute monoblastic leukemia using combination antifungal therapy including micafungin as a key drug. AB - While anti-cancer chemotherapy has improved the survival of patients with hematologic malignancies, it has also exposed such patients to the risk of life threatening infection due to neutropenia. In intensive chemotherapy for leukemia, invasive aspergillosis resulting in death is infrequently observed. In such cases, aggressive diagnostic and therapeutic intervention is required. Herein, we report a case of Aspergillus liver abscesses in a patient with acute monoblastic leukemia. The patient presented with febrile neutropenia and concomitantly with an elevated serum beta-D: -glucan level during chemotherapy. The abscesses were finally diagnosed by liver biopsy. Although antifungal monotherapy of voriconazole or liposomal amphotericin B, both of which are recommended for invasive aspergillosis, showed a poor response, when combined with micafungin, an echinocandin, both had a highly favorable effect against the infection. Therefore, our clinical experience suggests that the serum test is useful for the rapid diagnosis of invasive aspergillosis, especially in deep tissues, and that combination antifungal therapy with micafungin should be considered when initial monotherapy for fungal infection shows an insufficient effect. PMID- 20352381 TI - Essential roles of VLA-4 in the hematopoietic system. AB - Integrins are one of the major families of adhesion molecules and make various kinds of biological effects by mediating cell-cell and cell-matrix interactions. Among integrins, VLA-4 is expressed on many types of hematopoietic cells including stem/progenitor cells and it is considered as a critical regulator of adult hematopoiesis. Recent studies revealed that VLA-4 is not necessarily required for the development or maintenance of adult hematopoietic cells. On the other hand, it was proved that VLA-4 is essential for homeostasis of distribution of hematopoietic stem/progenitor cells (HSPCs) and mature lymphocytes in the body. The dynamic regulation of VLA-4 function is mediated by its conformational change, which is strictly linked to the interaction between alpha and beta cytoplasmic domains. The study using knockin mice showed that GFFKR sequence, a well-preserved motif in the alpha cytoplasmic domain of VLA-4, is critical for binding of alpha and beta cytoplasmic domains as well as regulation of hematopoietic cell distribution. Small molecules targeting this cytoplasmic interaction or ligand-VLA-4 interaction may become good candidates of new drugs for mobilization of hematopoietic stem cells. Several studies have suggested the impact of VLA-4 on chemotherapy sensitivity and prognosis in hematological malignancies, which awaits further investigations. PMID- 20352382 TI - Uncommon case of chronic myeloid leukemia with multiple myeloma. AB - We describe a 72-year-old woman who was diagnosed with asymptomatic multiple myeloma (MM) while being treated for Philadelphia (Ph)-positive chronic myeloid leukemia (CML) with imatinib mesylate (400 mg/day). The diagnosis of CML was based on the presence of the Ph chromosome and chimeric BCR-ABL messenger RNA. Three months after starting imatinib mesylate treatment, the patient achieved a complete cytogenetic response. However, bone marrow analysis at that time demonstrated plasmacytosis, and paraprotein (IgG, kappa-type) was also detected. Hypercalcemia, renal failure, anemia, and bone lesions were not observed, which suggested that asymptomatic MM had developed. The coexistence of CML and MM is an extremely uncommon event that has only been reported in 12 cases. We discuss the relationship between CML and MM. PMID- 20352383 TI - Minimally invasive versus classic procedures in total hip arthroplasty: a double blind randomized controlled trial. AB - BACKGROUND: For total hip arthroplasty (THA), minimally invasive surgery (MIS) uses a smaller incision and less muscle dissection than the classic approach (CLASS), and may lead to faster rehabilitation. QUESTIONS/PURPOSES: Does minimally invasive hip arthroplasty result in superior clinical outcomes? PATIENTS AND METHODS: In this double-blind randomized controlled trial, 120 consecutive primary noncemented THAs in 120 patients were assigned to one of two groups (MIS or CLASS). The randomization sequence was stratified for two groups of surgeons, ie, those using a posterolateral approach (PL-CLASS or PL-MIS) and those using an anterolateral approach (AL-CLASS or AL-MIS). Length of the incisions was 18 cm for the CLASS procedures. MIS incisions were extended at the skin level to 18 cm at the end of the procedure. The primary end point was the Harris hip score (HHS) at 6 weeks postoperatively. Patient-centered questionnaires were obtained preoperatively and after 6 weeks and 1 year. RESULTS: For the patients in the MIS group (average 7.8 cm incision length), statistically significant increased mean HHSs were seen compared with the CLASS group at 6 weeks and 1 year. This difference was small and mainly caused by the favorable results of the PL-MIS. In the MIS group, surgical time was longer. A learning curve was observed based on operation time and complication rate. Although not statistically significant, the perioperative complication rate was rather high in the (anterolateral) MIS group. CONCLUSIONS: The minimal invasive approach in THA did not show a clinically relevant superior outcome in the first postoperative year. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20352384 TI - Rotational references for total knee arthroplasty tibial components change with level of resection. AB - BACKGROUND: Various landmarks can guide tibial component rotational alignment in routine TKA, but with the deeper tibial resection levels common in complex primary and revision TKAs, it is unknown whether these landmarks remain reliable. QUESTIONS/PURPOSES: We asked whether three techniques for determining tibial component rotation based on local anatomic landmarks are reliable deeper tibial resection levels. PATIENTS AND METHODS: The femoral transepicondylar axis was identified by three independent reviewers on MR images of knees from 24 men and 24 women and transposed at a traditional tibial resection level and at the level of the proximal, middle, and distal parts of the proximal tibiofibular joint. Three axes were drawn on axial slices at these levels: the geometric center of the tibial plateau to the medial 1/3 of the tubercle, the posterior condylar line of the tibia, and the largest mediolateral dimension of the tibia. These lines were compared with the transposed femoral epicondylar axis line. RESULTS: The posterior condylar line of the tibia is the least variable local landmark for tibial component positioning at deep resection levels. CONCLUSIONS: Assuming the normal posterior condylar line of the tibia is visible at revision, setting the tibial component at 10 degrees external rotation with respect to the posterior condylar axis of the tibia gets the tibial component within 10 degrees of proper rotation in 86% to 98% of patients, even to the distal part of the proximal tibiofibular joint. The experienced surgeon then can adjust this position based on cues from an assortment of other axes. PMID- 20352385 TI - Femoral head-neck junction deformity is related to osteoarthritis of the hip. AB - BACKGROUND: Primary or idiopathic osteoarthritis (OA) of the hip has increasingly been attributed to the presence of presumably minor femoral or acetabular deformities that are not routinely identified. The alpha angle reflects one such deformity of the femoral neck and reflects a risk for femoroacetabular impingement, which in turn reportedly is associated with OA. If impingement is in fact associated with OA, then one might expect the mean alpha angle to be greater in patients with presumed idiopathic hip OA. QUESTIONS/PURPOSES: We therefore compared the alpha angle among a group of elderly patients with idiopathic OA with that in a control group of elderly individuals without OA. PATIENTS AND METHODS: We measured the alpha angles in 50 individuals (72 hips) with a mean age of 70 years (range, 60-84 years) with apparently idiopathic OA and compared their angles with those from a control group of 56 individuals without OA. The alpha angle was measured by means of radiographs of their hips using the Dunn view at 45 degrees flexion. RESULTS: The patients with OA had a greater percentage with abnormal alpha angles than did the normal subjects: 82% versus 30%, respectively. The mean alpha angle in the group with OA was larger than in the control subjects: 66.4 masculine (range, 28 degrees -108 degrees ) versus 48.1 masculine (range, 34 degrees -68 degrees ). CONCLUSIONS: Hips with presumably idiopathic OA had more abnormalities at the femoral head-neck junction than did the control hips without OA and may relate to the risk of OA developing. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20352386 TI - Do scores of the USMLE Step 1 and OITE correlate with the ABOS Part I certifying examination?: a multicenter study. AB - BACKGROUND: The US Medical Licensing Examination (USMLE) and Orthopaedic In Training Examination (OITE) are commonly used to select medical students or residents, respectively. Knowing how well these examinations predict performance on the American Board of Orthopaedic Surgery (ABOS) Part I certifying examination is important to provide evaluations for medical students and residents. Previous studies comparing the OITE scores with the ABOS Part 1 scores have been limited to one program. QUESTIONS/PURPOSES: Therefore, we compared the scores on the USMLE Step 1 and OITE examinations with those on the ABOS Part I certifying examination using data from four ACGME approved residency programs. METHODS: We reviewed 202 resident files from 1996 to 2008 from four programs in the same geographic region. Of those, 181 (90%) had complete records. De-identified data were used to compare USMLE Step 1 scores, OITE percentile rank scores, and ABOS Part I percentile rank scores. Pearson coefficients and receiver operator curves were calculated to assess the relationships between tests. RESULTS: We found a correlation of 0.53 between the USMLE Step 1 and ABOS Part I, and an average correlation of 0.50 for postgraduate years (PGY) 2 through 5 OITE scores and ABOS Part I. There was a stepwise increase in correlation from PGY 2 through PGY 5 between the OITE scores and ABOS scores. Those who averaged in the 27th percentile or lower on the OITE had a 57% chance of failing the ABOS Part I examination. CONCLUSION: USMLE Step 1 scores correlated with ABOS Part I certifying examination scores, and we therefore believe it may be used as one factor in resident selection. Use of the OITE scores in guiding education and feedback appears to be justified. PMID- 20352387 TI - In brief: classifications in brief: Mirels' classification: metastatic disease in long bones and impending pathologic fracture. PMID- 20352388 TI - Retrospective analysis of infection rate after early reoperation in total hip arthroplasty. AB - BACKGROUND: Infection is a devastating complication of total hip arthroplasty (THA). Unavoidable reoperation during the acute recovery phase of hip arthroplasty has the potential for an increased infection rate but the risk is not well established nor is the fate of these infected hips. QUESTIONS/PURPOSES: We therefore report the infection rate for patients undergoing THA who returned to the operating room within 90 days of his or her index procedure for any surgical intervention on the same hip. METHODS: We identified 60 patients undergoing THA referred to or treated at our institution who required an unplanned and unavoidable return to the operating room during the acute recovery phase. The complications of the initial surgery that resulted in reoperation included instability, periprosthetic fracture, retained hardware, and nerve exploration. We then retrospectively reviewed the medical records to determine the infection rate and implant survivorship. The minimum followup was 1 month (average, 3.7 years; range, 1 month to 7 years) and included all patients who required resection before a minimum 2-year followup. RESULTS: The infection rate for this cohort was 20 of 60 (33%). Six of these 20 retained their implants at 2 years after the reoperation and were considered infection-free. Two-stage reimplantation or resection was eventually performed in 14 of the infected patients. CONCLUSIONS: A high percentage of patients undergoing THA developed a deep infection after unavoidable reoperation during the acute recovery phase. The reasons for the reoperations were potentially modifiable complications and situations that deserve further investigation to delineate protocols to minimize the risk of infection in these patients. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 20352389 TI - Chitosan sponges to locally deliver amikacin and vancomycin: a pilot in vitro evaluation. AB - BACKGROUND: Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality. QUESTIONS/PURPOSES: We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to debridement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa? METHODS: We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin. RESULTS: Amikacin concentration was 881.5 microg/mL after 1 hour with a gradual decline to 13.9 microg/mL after 72 hours. Vancomycin concentration was 1007.4 microg/mL after 1 hour with a decrease to 48.1 microg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge. CLINICAL RELEVANCE: Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections. PMID- 20352390 TI - Strategies in biologic augmentation of rotator cuff repair: a review. AB - BACKGROUND: Degenerative rotator cuff tears are increasing with the aging population, and healing is not uniform after surgery. Rotator cuffs may show improved healing when biologic factors are added during surgery. QUESTIONS/PURPOSES: We asked: (1) What cellular processes are involved in normal bone-to-tendon healing? (2) What approaches are being developed in tendon augmentation? (3) What approaches are being developed with the addition of growth factors? METHODS: We reviewed research in relating to biologic augmentation and cellular processes involved in rotator cuff repair, focusing on animal models of rotator cuff repair and nonrandomized human trials. RESULTS: Regular bone-to tendon healing forms a fibrous junction between tendon and bone that is distinct from the original bone-to-tendon junction. Tendon augmentation with cellular components serves as scaffolding for fibroblastic cells and a possible source of growth factors and fibroblastic cells. Extracellular matrices provide a scaffold for incoming fibroblastic cells, although current research does not conclusively confirm which if any of these scaffolds enhance repair owing in part to intermanufacturer variations and the limited human research. Growth factors and platelet-rich-plasma are established in other fields of research and may enhance repair but have not been rigorously tested. CONCLUSIONS: There is potential application of biologic augmentation to improve healing after rotator cuff repair. However, research in this field is still inconclusive and has not been sufficiently demonstrated to merit regular clinical use. Future human trials can elucidate the use of biologic augmentation in rotator cuff repairs. PMID- 20352391 TI - Minimal incision surgery as a risk factor for early failure of total hip arthroplasty. AB - BACKGROUND: Minimal incision total hip arthroplasty (MI THA) techniques were developed to decrease postoperative pain and recovery time. Although these techniques have increased in popularity, the long-term survivorship of these procedures is unknown. QUESTIONS/PURPOSES: We therefore investigated whether the time to revision in our referral practice was shorter for patients who underwent primary MI THA compared to primary traditional THA. METHODS: We retrospectively reviewed 46 revision THAs performed during a 3-year period. We excluded revisions performed for infection and rerevisions. Patients with incisions less than or equal to 10 cm were defined as having had MI THA. Fifteen of the 46 patients (33%) had undergone primary MI THA. At the time of primary index THA, the mean ages of the MI and non-MI patients were 65 years and 55 years, respectively. RESULTS: The mean time to revision was 1.4 years for the MI patients compared with 14.7 years for the non-MI patients. Twelve of the 15 patients having MI THA required revision within 2 years of primary THA compared to 4 of the 31 patients without MI surgery (OR = 26.5, 95% CI 4.4-160.0). There were no differences between the groups with regard to age, gender, or body mass index. The most common reasons for revision in the MI THA group were intraoperative fracture and failure of femoral component osseointegration. CONCLUSIONS: Our data suggest MI THA may be a risk factor for early revision surgery and the long-term survival therefore may be lower than that for non-MI surgery. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20352392 TI - Assessment of adherence and healthcare costs of insulin device (FlexPen) versus conventional vial/syringe. AB - INTRODUCTION: Diabetes is difficult to manage and treatment involves significant lifestyle adjustments. Unlike the traditional method of insulin administration via the vial and syringe method, insulin pens might be perceived as less cumbersome and have potential to significantly increase patient adherence. METHODS: Using "real world" data, we examined the differences in adherence and costs between diabetic patients using an insulin FlexPen (Novo Nordisk Inc, Princeton, NJ, USA) and those using traditional vial and syringe administration. Using a retrospective analysis of health insurance claims data between the years 2003 and 2008, we examined patients in the FlexPen cohort and analog vial cohort. Propensity score matching was used to match these cohorts (n=532 in each) according to baseline characteristics. RESULTS: Adjusted mean medication possession ratio when switched to FlexPen improved by 22 percentage points versus 13 percentage points when continuing to use vials (P=0.001). Diabetes-related healthcare costs when switched to FlexPen versus continuing on to use vials ($3970 vs. $4838, respectively, P=0.9368) and total healthcare costs ($13,214 vs. $13,212, respectively, P=0.9473) were not statistically different. CONCLUSION: Without significant addition to the cost, insulin administration with FlexPen is associated with an improved adherence among patients who switched from vial-based insulin administration. PMID- 20352393 TI - Identification of microRNAs associated with hyperthermia-induced cellular stress response. AB - MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes. Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly, only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2-the core functional unit of RNA silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially express these miRNAs when exposed to hyperthermia. PMID- 20352394 TI - Evaluation of cerebellar and cerebral volume in migraine with aura: a stereological study. AB - Migraine is associated with an increased risk of deep white matter lesions and subclinical posterior circulation infarcts. A significant association between deep white matter hyperintensities and cerebral atrophy is true for various neurological diseases; it was not specifically proven in migraine. The aim of this study was to evaluate the cerebellar and cerebral volume and volume ratios for cerebellum using the Cavalieri principle. We also aimed to examine whether migraine with aura causes cerebellar and cerebral atrophy. Twenty three right handed patients with migraine with aura diagnosed by means of the International Headache Society criteria and 24 age-matched subjects whose only health problem was headache due to rhinosinusitis and tension type headache were included in the study. Measurements of the cerebellar and cerebral volumes as well as cerebellar/cerebral volume ratios were made using Cavalieri's principle by utilizing the point-counting methods. There were no significant differences between the volumes of cerebrum, cerebellum, and the ratio of cerebellum to cerebrum for males (p = 0.05, p = 0.10, and p = 0.64, respectively) and for females (p = 0.18, p = 0.89, and p = 0.24, respectively). Our results suggest that patients with migraine with aura do not have a significant difference in cerebellar and cerebral volumes and cerebellar/cerebral volume ratios compared to the non-migraine group. PMID- 20352395 TI - Balance control in sitting and standing in children and young adults with benign cerebellar tumors. AB - Children and young adolescents with chronic surgical cerebellar lesions show persistent balance control problems during standing when lesions affect the deep cerebellar fastigial and adjacent interposed nuclei. The purpose of this study is to confirm that the same lesion sites are also associated with permanent signs of trunkal ataxia during sitting. A second aim is to demonstrate that examining the postural control of patients while sitting or standing on a foam cushion may constitute a simple clinical exam yielding results commensurate to a more involved dynamic posturography exam. Balance control was assessed in 16 patients after surgery of a benign cerebellar tumor in chronic state and healthy age- and gender-matched control subjects. Using an ultrasound-based kinematic recording system, trunkal and shoulder sway was measured during sitting and standing in different conditions. High-resolution MRI scans were acquired in the cerebellar patients. Voxel-wise statistical lesion symptom mapping was performed to compare lesioned areas between affected and unaffected patients in a given condition using chi2 tests. During sitting, 56% of cerebellar patients exhibited trunkal sway outside the range of healthy controls, and 87.5% of cerebellar patients revealed abnormal sway patterns during standing. Abnormalities were most pronounced when visual information was absent, and somatosensory information became unreliable and/or when the base of support along the medio-lateral axis was minimized during tandem stance. Lesion symptom mapping revealed that pathological values in the behavior data were more likely in patients with surgical lesions involving the fastigial nuclei (NF) and adjacent interposed nuclei (NI). In patients with surgery <1-year lesions of the inferior cerebellar vermis also had an impact on balance function. Our results corroborate previous evidence that the extent of permanent damage to the deep cerebellar nuclei greatly impacts on the recovery on balance function. PMID- 20352396 TI - Progression of atrophy in Alzheimer's disease and related disorders. AB - Longitudinal MRI is a powerful tool that allows the assessment of progression of brain changes over multiple imaging time-points and has been increasingly employed in the study of neurodegenerative dementias, particularly Alzheimer's disease (AD). Early studies demonstrated that AD was associated with increased rates of whole brain loss and hippocampal atrophy. A number of sophisticated voxel-level techniques have now been developed that have provided additional information describing regional atrophy over time in the temporal, parietal, and frontal lobes in AD. Studies have also focused on subjects in the prodromal phase of AD in order to describe the earliest changes that are occurring in the brain. Atrophy has been shown to start in the medial temporal lobes and fusiform gyrus at least 3 years before subjects reach a diagnosis of AD, and then spread to the posterior temporal lobes and parietal lobes, and then eventually the frontal lobes. These patterns of atrophy correlate well with the progression of neurofibrillary tangles observed on pathology. Rates of atrophy have also been shown to accelerate over the course of the disease as a subject progresses from cognitively normal to a diagnosis of AD. Similar techniques have also been applied to other neurodegenerative diseases, such as frontotemporal dementia which show higher rates of atrophy and different patterns of progression to those observed in AD. Hence, longitudinal MRI shows promise as a biomarker of disease progression in neurodegenerative disease. PMID- 20352397 TI - Research training of students in minority and international settings: lessons learned from cancer epidemiology education in special populations. AB - This article describes the development and evaluation of an NCI-sponsored short term summer cancer research education program. The study questions examined: the feasibility of conducting a cancer education program in special populations at multiple US and international field sites for masters students; the merit and worth that students and faculty attribute to the program; and students' scholarly and cancer-related career outcomes. Developing a new curriculum, increasing the pool of mentors, utilizing and increasing the number of field sites, and program dissemination were also evaluated. Evidence of the program's success included students' completion of field experiences at multiple sites and their subsequent 70% project-related publication rate, with 79% of trainees reporting themselves as likely to pursue future cancer-related careers. Evaluation-guided future plans for the program include implementing faculty development to further enhance the program outcomes. PMID- 20352398 TI - The role of medical interpretation on breast and cervical cancer screening among Asian American and Pacific Islander women. AB - We examined whether the impact of medical interpretation services was associated with the receipt of a mammogram, clinical breast exam, and Pap smear. We conducted a large cross-sectional study involving four Asian American and Pacific Islander (AAPI) communities with high proportions of individuals with limited English proficiency (LEP). Participants were recruited from community clinics, churches and temples, supermarkets, and other community gathering sites in Northern and Southern California. Among those that responded, 98% completed the survey rendering a total of 1,708 AAPI women. In a series of multivariate logistic regression models, it was found that women who typically used a medical interpreter had a greater odds of having received a mammogram (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.21, 2.83), clinical breast exam (OR = 3.03; 95% CI = 1.82, 5.03), and a Pap smear (OR = 2.34; 95% CI = 1.38, 3.97) than those who did not usually use an interpreter. The study provides support for increasing language access in healthcare settings. In particular, medical interpreters may help increase the utilization of breast and cervical cancer screening among LEP AAPI women. PMID- 20352399 TI - Filming the family: a documentary film to educate clinicians about family caregivers of patients with brain tumors. AB - The objective of this paper is to evaluate the educational value of a documentary film about family caregiving for patients with brain tumors. The method used in this study is a pre-post survey among neurosurgeons, neuro-oncologist, and other clinician viewers. Viewers evaluated the film highly and reported an intention to change their practice as a result of watching the film. Following viewing, participants felt more strongly that "all families of patients with brain cancers should meet with a social worker" (P = 0.01) and that "family caregivers greatly impact the health of patients" (P = 0.002), and they were less likely to believe that "supporting family caregivers is primarily someone else's job" (P = 0.009). A documentary film about family caregiving is an effective educational tool to increase awareness among neurosurgery/neuro-oncology clinicians about the importance and needs of family caregivers of patients with brain tumors. PMID- 20352400 TI - The Holy Grail of anatomic and functional MR urography in children. PMID- 20352401 TI - Tracheal side effects following fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia. PMID- 20352404 TI - Effect of bacterial inoculation, plant genotype and developmental stage on root associated and endophytic bacterial communities in potato (Solanum tuberosum). AB - Beneficial bacteria interact with plants by colonizing the rhizosphere and roots followed by further spread through the inner tissues, resulting in endophytic colonization. The major factors contributing to these interactions are not always well understood for most bacterial and plant species. It is believed that specific bacterial functions are required for plant colonization, but also from the plant side specific features are needed, such as plant genotype (cultivar) and developmental stage. Via multivariate analysis we present a quantification of the roles of these components on the composition of root-associated and endophytic bacterial communities in potato plants, by weighing the effects of bacterial inoculation, plant genotype and developmental stage. Spontaneous rifampicin resistant mutants of two bacterial endophytes, Paenibacillus sp. strain E119 and Methylobacterium mesophilicum strain SR1.6/6, were introduced into potato plants of three different cultivars (Eersteling, Robijn and Karnico). Densities of both strains in, or attached to potato plants were measured by selective plating, while the effects of bacterial inoculation, plant genotype and developmental stage on the composition of bacterial, Alphaproteobacterial and Paenibacillus species were determined by PCR-denaturing gradient gel electrophoresis (DGGE). Multivariate analyses revealed that the composition of bacterial communities was mainly driven by cultivar type and plant developmental stage, while Alphaproteobacterial and Paenibacillus communities were mainly influenced by bacterial inoculation. These results are important for better understanding the effects of bacterial inoculations to plants and their possible effects on the indigenous bacterial communities in relation with other plant factors such as genotype and growth stage. PMID- 20352409 TI - A FRAX(r) model for the assessment of fracture probability in Belgium. AB - A country-specific FRAX(r) model was developed from the epidemiology of fracture and death in Belgium. Fracture probabilities were identified that corresponded to currently accepted reimbursement thresholds. INTRODUCTION: The objective of this study was to evaluate a Belgian version of the WHO fracture risk assessment (FRAX(r)) tool to compute 10-year probabilities of osteoporotic fracture in men and women. A particular aim was to determine fracture probabilities that corresponded to the reimbursement policy for the management of osteoporosis in Belgium and the clinical scenarios that gave equivalent fracture probabilities. METHODS: Fracture probabilities were computed from published data on the fracture and death hazards in Belgium. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck bone mineral density (BMD). Fracture probabilities were determined that were equivalent to intervention (reimbursement) thresholds currently used in Belgium. RESULTS: Fracture probability increased with age, lower BMI, decreasing BMD T-score and all clinical risk factors used alone or combined. The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current reimbursement guidelines ranged from approximately 7.5% at the age of 50 years to 26% at the age of 80 years where a prior fragility fracture was used as an intervention threshold. For women at the threshold of osteoporosis (femoral neck T-score = 2.5 SD), the respective probabilities ranged from 7.4% to 15%. Several combinations of risk-factor profiles were identified that gave similar or higher fracture probabilities than those currently accepted for reimbursement in Belgium. CONCLUSIONS: The FRAX(r) tool has been used to identify possible thresholds for therapeutic intervention in Belgium, based on equivalence of risk with current guidelines. The FRAX(r) model supports a shift from the current DXA based intervention strategy, towards a strategy based on fracture probability of a major osteoporotic fracture that in turn may improve identification of patients at increased fracture risk. The approach will need to be supported by health economic analyses. PMID- 20352408 TI - Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. AB - The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options. PMID- 20352410 TI - Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system. AB - The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher. INTRODUCTION: The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine. METHODS: The study cohort comprised 196 females and 163 males (age range 67-89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system. RESULTS: Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction. CONCLUSION: Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration. PMID- 20352411 TI - Alcohol expectancy increases positive responses to cigarettes in young, escalating smokers. AB - RATIONALE: A large proportion of smokers consolidate their smoking patterns during young adulthood, and it is possible that the high rates of drinking found in this age group may facilitate the transition from nondaily to daily cigarette use. OBJECTIVE: The primary aim of this study was to examine how alcohol alters the subjective effects of smoking in heavy-drinking young adults (age 21-25) who are still at an experimental stage of smoking but show recent increases in their smoking behavior. METHODS: Using a within-subject design, we examined whether alcohol or the expectation of receiving alcohol increased either subjective responses to smoking or the amount smoked. Subjects participated in three sessions, in which they received alcohol (0.08 g/dL targeted blood alcohol level), a taste-masked placebo presented as alcohol, or a mixer beverage not presented as alcohol. Measures included positive and negative subjective reactivity (e.g., satisfaction, nausea, craving relief, and enjoyment of airway sensations) associated with smoking a single cigarette and subsequent ad lib smoking behavior. RESULTS: Both conditions in which the subjects expected to receive alcohol increased positive effects of smoking (satisfaction, calm, and taste), compared to the mixer beverage. Alcohol, compared to the placebo and mixer beverages, decreased negative effects (nausea) associated with smoking a cigarette and increased subsequent smoking. CONCLUSIONS: This initial study has implications for understanding how alcohol and the expectation of alcohol improves the experience of smoking in nondaily smokers who are still at an experimental stage of smoking. PMID- 20352412 TI - Effects of alcohol preload on attentional bias towards cocaine-related cues. AB - BACKGROUND: Drug and alcohol users have an 'attentional bias' for substance related cues, which is likely to reflect the incentive-motivational properties of those cues. Furthermore, administration of an alcohol preload increases attentional bias for alcohol and tobacco-related cues in heavy drinkers and tobacco smokers, respectively. The present study investigated attentional bias for cocaine cues in cocaine users and non-users following administration of either alcohol or placebo. METHOD: Thirty-two regular cocaine users and 40 non users took part. Participants were administered alcohol or placebo, and administration was double blind. After drink administration, a Visual Probe task and Modified Stroop task were used to assess attentional bias. Subjective craving and alcohol outcome expectancies were also measured. RESULTS: There was a significant interaction between group and drink type on the visual probe task indicating that cocaine users who had received alcohol had increased attentional bias for cocaine pictures compared to non-users and cocaine users who received placebo. The cocaine Stroop revealed no differences between cocaine users and non users, and no effects of alcohol in either group. CONCLUSIONS: Alcohol preload in regular cocaine users increases attentional bias for cocaine cues. However, cocaine users who received placebo did not show attentional bias for cocaine stimuli. Future research should investigate the effects of alcohol preload on attentional bias in cocaine-dependent individuals. PMID- 20352413 TI - Modafinil effects on reinstatement of methamphetamine seeking in a rat model of relapse. AB - RATIONALE: Modafinil (Provigil) is a wake-promoting drug characterized by cognitive enhancing abilities. Recent clinical data have supported the use of modafinil for treatment of chronic psychostimulant addiction and relapse prevention. MATERIALS AND METHODS: We used an intravenous methamphetamine (meth) self-administration procedure to assess the dose-dependent effects of modafinil on reinstatement following abstinence and after extinction on conditioned-cue and meth-primed reinstatement of meth seeking. RESULTS: Modafinil attenuated active lever responding in multiple reinstatement conditions-context-induced, conditioned cue, and meth prime. The most pronounced and consistent effect was on meth-primed reinstatement, and modafinil did not reinstate meth seeking when tested alone. DISCUSSION: These findings support clinical findings in humans that modafinil may be an effective therapeutic agent for the prevention of relapse in abstinent meth users. PMID- 20352417 TI - Use of wire as a snare for endovascular retrieval of displaced or stretched coils: rescue from a technical complication. AB - INTRODUCTION: The displacement or stretching of coils during coiling of cerebral aneurysms is not an unusual technical complication, thus causing potentially disastrous consequences. Here, a simple technique using a wire as a snare for the removal of displaced and stretched coils is described. METHODS: The simple wire technique was used to remove a coil displaced in the distal M2 that a microsnare had failed to capture and another coil stretched during the coiling of cerebral aneurysms. RESULTS: The displaced coil lodged in the distal small cerebral vessel was entwined and removed using a microwire that was shaped manually as a pigtail at the tip. To retrieve the stretched coil, where a proximally stretched portion of the coil still remains in the delivery catheter with the distal portion placed in the aneurysm, a guidewire with a J-shaped tip was used. The coil was hooked and entwined by twisting this wire tip, which could be removed without difficulty. CONCLUSION: This simple technique using a wire as a snare could be a useful method for removing displaced or stretched coils in selected cases. PMID- 20352415 TI - Effects of modafinil and methylphenidate on visual attention capacity: a TVA based study. AB - INTRODUCTION: Theory of visual attention (TVA; Bundesen 1990) whole report tasks allow the independent measurement of visual perceptual processing speed and visual short-term memory (vSTM) storage capacity, unconfounded by motor speed. This study investigates how cognitive enhancing effects of psychostimulants depend on baseline performance and individual plasma levels. MATERIALS AND METHODS: Eighteen healthy volunteers (aged 20-35 years) received single oral doses of either 40 mg methylphenidate, 400 mg modafinil or placebo in a counterbalanced, double-blind crossover design. A whole report of visually presented letter arrays was performed 2.5-3.5 h after drug administration, and blood samples for plasma level analysis were taken. RESULTS: Methylphenidate and modafinil both enhanced perceptual processing speed in participants with low baseline (placebo) performance. These improvements correlated with subjective alertness. Furthermore, we observed differential plasma level-dependent effects of methylphenidate in lower and higher performing participants: higher plasma levels led to a greater improvement in low-performing participants and to decreasing improvement in high-performing participants. Modafinil enhanced visual short-term memory storage capacity in low-performing participants. CONCLUSIONS: This is the first pharmacological investigation demonstrating the usefulness of a TVA task for high-resolution and repeated cognitive parameter estimation after cognitive-enhancing medication. Our results confirm previous findings of attentional capacity improvements in low performers and extend the baseline dependency model to methylphenidate. Plasma level-dependent effects of psychostimulants can be modelled on an inverted U-shaped dose-response relationship, which is highly relevant to predict cognitive enhancing and detrimental effects of psychostimulants in patients with cognitive deficits (e.g., attention deficit hyperactivity disorder) and healthy volunteers (e.g., self-medicating academics). PMID- 20352418 TI - Intracranial stenting in atherosclerotic disease-recent results and challenges to face. AB - Intracranial stenting is increasingly used as an add-on to medical therapy despite the fact that the overall clinical benefit remains a matter of debate, since we lack results of randomized trials. Decision making on interventional treatment is made on the grounds of the anticipated risk of stroke with antiplatelet medication on one hand and on the experience with stent treatment based on data from case series and registries on the other hand. This review will summarize the current knowledge on both topics serving as the fundament of patient selection for intracranial stenting. A second objective is to highlight some specific problems that are encountered when treating patients interventionally. Procedure-related complication rates and rates of in stent stenoses are still too high to be confident that endovascular treatment is superior to medical therapy of symptomatic stenoses. Optimization of patient selection criteria, stent technology, and periprocedural management are necessary to become undoubtedly competitive with antiplatelet therapy. With the current stage of development, interventional treatment of intracranial stenoses should be confined to specialized centers with a high expertise in neurovascular procedures. PMID- 20352419 TI - Hippocampal development at gestation weeks 23 to 36. An ultrasound study on preterm neonates. AB - INTRODUCTION: During fetal development, the hippocampal structures fold around the hippocampal sulcus into the temporal lobe. According to the literature, this inversion should be completed at gestation week (GW) 21. Thereafter, the hippocampal shape should resemble the adult shape. However, incomplete hippocampal inversion (IHI) is found in 19% of the common population. The aim of this study was to study fetal hippocampal development by examining neonates born preterm. METHODS: We analyzed cranial ultrasound examinations, performed as a part of the routine assessment of all preterm infants, over a 3-year period and excluded the infants with brain pathology. The final material consisted of 158 children born <35 GW. A rounded form (the ratio between the horizontal and vertical diameters of the hippocampal body or=25 GW was statistically highly significant (p < 0.001). The frequency of bilateral IHI was highest in the youngest age group. In the other groups, the left-sided IHI was the most common. CONCLUSION: In about 50% of the neonates, hippocampal inversion is not completed up to GW 24; but from 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population. PMID- 20352414 TI - The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. AB - BACKGROUND: Initial hypotheses regarding the role of the kappa opioid system in drug addiction suggested that kappa receptor stimulation had anti-addictive effects. However, recent research suggests that kappa receptor antagonists may reverse motivational aspects of dependence. In the present review, we revisit the studies that measured the effects of kappa receptor ligands on the reinforcing and rewarding effects of drugs and postulate underlying neurobiological mechanisms for these effects to elaborate a more complex view of the role of kappa receptor ligands in drug addiction. RESULTS: The review of studies indicates that kappa receptor stimulation generally antagonizes the acute reinforcing/rewarding effects of drugs whereas kappa receptor blockade has no consistent effect. However, in a drug dependent-like state, kappa receptor blockade was effective in reducing increased drug intake. In animal models of reinstatement, kappa receptor stimulation can induce reinstatement via a stress like mechanism. Results in conditioned place preference/aversion and intracranial self-stimulation indicate that kappa receptor agonists produce, respectively, aversive-like and dysphoric-like effects. Additionally, preclinical and postmortem studies show that administration or self-administration of cocaine, ethanol, and heroin activate the kappa opioid system. CONCLUSION: kappa receptor agonists antagonize the reinforcing/rewarding effects of drugs possibly through punishing/aversive-like effects and reinstate drug seeking through stress-like effects. Evidence suggests that abused drugs activate the kappa opioid system, which may play a key role in motivational aspects of dependence. Kappa opioid systems may have an important role in driving compulsive drug intake. PMID- 20352420 TI - Iron uptake and metabolism in pseudomonads. AB - Pseudomonads are ubiquitous Gram-negative gamma proteobacteria known for their extreme versatility and adaptability. Some are plant pathogens (Pseudomonas syringae) which have to survive on the surface of leaves while others can colonize the rhizosphere or survive in soil (Pseudomonas fluorescens, Pseudomonas putida), and one species, Pseudomonas entomophila, is an insect pathogen. The most investigated species, Pseudomonas aeruginosa, is known to be an opportunistic pathogen able to infect plants, nematodes, insects, and mammals, including humans. Like for other bacteria, iron is a key nutrient for pseudomonads. The fluorescent pseudomonads produce siderophores, the best known being the fluorescent high-affinity peptidic pyoverdines. Often diverse secondary siderophores of lower affinity are produced as well (pyochelin, pseudomonin, corrugatins and ornicorrugatins, yersiniabactin, and thioquinolobactin). Reflecting their large capacity of adaptation to changing environment and niche colonization, pseudomonads are able to obtain their iron from heme or from siderophores produced by other microorganisms (xenosiderophores) via the expression of outer membrane TonB-dependent receptors. As expected, iron uptake is exquisitely and hierarchically regulated in these bacteria. In this short review, the diversity of siderophores produced, receptors, and finally the way iron homeostasis is regulated in P. aeruginosa, P. syringae, P. putida, and P. fluorescens, will be presented and, when possible, put in relation with the lifestyle and the ecological niche. PMID- 20352421 TI - The trans/cis ratio of unsaturated fatty acids is not applicable as biomarker for environmental stress in case of long-term contaminated habitats. AB - Cis-trans isomerization of unsaturated fatty acids is a crucial adaptive reaction of Pseudomonas and Vibrio species to toxic organic compounds or other environmental stress factors. In order to test the long-term performance of this adaptive mechanism as well as to assess its application as biomarker for environmental contamination studies were performed in batch cultures and in continuously running sand columns, simulating long-term contamination with bisphenol A (BPA). In short-term grown batch cultures a high correlation between trans/cis ratio and added BPA concentration and toxicity was observed. In contrary, this did not occur in the case of long-term sand columns. An increase in trans/cis ratio of unsaturated fatty acids only appeared in a limited period of time. Afterwards the trans/cis ratio reached the values measured for non stressed cultures. Cis-trans isomerization is only an urgent response mechanism that is later substituted by other adaptive mechanisms. Therefore, it can be concluded that the trans/cis ratio of unsaturated fatty acids was shown not to be an appropriate biomarker for durable stress in the environment. PMID- 20352422 TI - Properties and applications of microbial beta-D-xylosidases featuring the catalytically efficient enzyme from Selenomonas ruminantium. AB - Xylan 1,4-beta-D-xylosidase catalyzes hydrolysis of non-reducing end xylose residues from xylooligosaccharides. The enzyme is currently used in combination with beta-xylanases in several large-scale processes for improving baking properties of bread dough, improving digestibility of animal feed, production of D-xylose for xylitol manufacture, and deinking of recycled paper. On a grander scale, the enzyme could find employment alongside cellulases and other hemicellulases in hydrolyzing lignocellulosic biomass so that reaction product monosaccharides can be fermented to biofuels such as ethanol and butanol. Catalytically efficient enzyme, performing under saccharification reactor conditions, is critical to the feasibility of enzymatic saccharification processes. This is particularly important for beta-xylosidase which would catalyze breakage of more glycosidic bonds of hemicellulose than any other hemicellulase. In this paper, we review applications and properties of the enzyme with emphasis on the catalytically efficient beta-D-xylosidase from Selenomonas ruminantium and its potential use in saccharification of lignocellulosic biomass for producing biofuels. PMID- 20352423 TI - Effects of chemically and electrochemically dosed chlorine on Escherichia coli and Legionella beliardensis assessed by flow cytometry. AB - The present study reports the disinfection effects of chemically and electrochemically dosed chlorine on two models for typical water-borne bacteria (Escherichia coli and Legionella beliardensis) by plating and flow cytometry (FCM) in combination with different fluorescence dyes. The residual effect on various cell functions, including cultivability, esterase activity, membrane polarization, and integrity, was tested at different free chlorine concentrations. In comparison, chemical disinfection yielded on average 60% more E. coli cells entering the viable but nonculturable (VBNC) state than electrochemical disinfection. Here, VBNC is defined as those cells with intact cell membrane but which cannot be cultured on solid nutrient agar plates. L. beliardensis was about five times more resistant to chlorine disinfection than E. coli. The results also suggested the two methods result in different disinfection mechanisms on L. beliardensis, i.e., chemically dosed chlorine targeted cell membrane integrity before enzyme activity, while electrochemically dosed chlorine acted the other way round. In addition, both bacteria lost the integrity of their cell membranes at three times lower chlorine concentration over a longer contact time (i.e., 40 vs. 10 min) by the chemical method. Our results showed that FCM is an appropriate tool to evaluate the effects of water disinfection and the percentage of cells in VBNC in a matter of hours. Electrochemical disinfection is suggested to be a favorable alternative for chemical disinfection. PMID- 20352425 TI - Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes. AB - Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness. PMID- 20352428 TI - Th17 cells: positive or negative role in tumor? AB - Th17 cells have been recently identified as a distinct Th cell lineage and found in an experimental animal model of cancer and in human cancers, but whether these cells promote tumor growth or regulate antitumor responses remains controversial. This review provides a summary of the current literature regarding interleukin (IL)-17/IL-23 and Th17 cells in cancer and discusses their potential roles in cancer development. Finally, we note several issues in this research area that must be resolved before the design of novel therapeutic approaches specifically targeting Th17 cells in cancer become feasible. PMID- 20352427 TI - Elastography: modality-specific approaches, clinical applications, and research horizons. AB - Manual palpation has been used for centuries to provide a relative indication of tissue health and disease. Engineers have sought to make these assessments increasingly quantitative and accessible within daily clinical practice. Since many of the developed techniques involve image-based quantification of tissue deformation in response to an applied force (i.e., "elastography"), such approaches fall squarely within the domain of the radiologist. While commercial elastography analysis software is becoming increasingly available for clinical use, the internal workings of these packages often remain a "black box," with limited guidance on how to usefully apply the methods toward a meaningful diagnosis. The purpose of the present review article is to introduce some important approaches to elastography that have been developed for the most widely used clinical imaging modalities (e.g., ultrasound, MRI), to provide a basic sense of the underlying physical principles, and to discuss both current and potential (musculoskeletal) applications. The article also seeks to provide a perspective on emerging approaches that are rapidly developing in the research laboratory (e.g., optical coherence tomography, fibered confocal microscopy), and which may eventually gain a clinical foothold. PMID- 20352429 TI - Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells. AB - Peritoneal metastasis is a distinct pathologic characteristic of advanced epithelial ovarian cancer (EOC), which is the most deadly disease of the female reproductive tract. The inflammatory environment of the peritoneum in EOC contains abundant macrophages, activated thrombin, and thrombin-associated receptors. However, little is known about the mechanism by which the thrombin macrophages interaction contributes to tumor invasion and metastasis. We investigated the phenotype and cytokine/chemokine expression of thrombin-treated peripheral blood monocytes (MOs)/macrophages, it was found that the phenotype of MOs was altered toward a TAM-like macrophage CD163(high)IL-10(high)CCL18(high)IL 8(high) after thrombin stimulation. By Matrigel invasion assay, the conditioned medium of thrombin-stimulated MOs accelerated remarkable invasion of ES-2, SKOV3, and HO-8910, which was similar to invasive cell numbers of ascites stimuli (P < 0.05) and higher than MOs medium alone (P < 0.05). IL-8 was proposed as the major chemoattractant mediating EOC invasion based on MOs mRNA and protein expression profiling. It was observed that anti IL-8 monoclonal neutralizing antibody attenuated EOC cell invasion in a concentration-dependent manner. Increased transcriptional activation of NF-kappaB p50/p65 was identified in thrombin treated MOs. This study provided insight the role of thrombin in the regulation of EOC peritoneal invasion via "educating" MOs. PMID- 20352431 TI - Prognostic significance of CD95, P53, and BCL2 expression in extranodal non Hodgkin's lymphoma. AB - Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkin's lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the stomach (N = 31). Paraffin-embedded specimens were analyzed immunohistochemically for CD95, BCL2, and P53 expression. Multivariate analysis revealed that in DLBCLs, positive CD95 and negative BCL2 expression were independent prognostic factors for overall survival. We reached the same conclusion for MALTLs, with positive CD95 and negative P53 expression. In DLBCLs, the 5-year overall survival rate was 71.5% for the CD95-positive cases and 35% for the CD95-negative cases (p = 0.004) and the 5-year overall survival was significantly better in BCL2-negative cases (70.8%) when compared to BCL2-positive cases (37%; p = 0.009). In MALTLs, the 5 year overall survival rate for the CD95-positive and CD95-negative groups was 89.5% and 42.9%, respectively (p = 0.004) and the 5-year overall survival rate was 50% for the P53-positive cases and 88.9% for the P53-negative cases (p = 0.016). In conclusion, positive CD95 expression proved to be a good prognostic factor of overall survival in both extranodal DLBCLs and MALTLs. In contrast, positive expression of BCL2 and P53 was found to be unfavorably associated with survival in extranodal DLBCLs and MALTLs, respectively. PMID- 20352430 TI - Complications of definitive open reduction and internal fixation of pilon fractures of the distal tibia. AB - A series of 49 pilon fractures in a tertiary referral centre treated definitively by open reduction and internal fixation have been assessed and the complications of such injuries examined. A retrospective analysis of case notes, radiographs and computerised tomographs over a seven-year period from 1999-2006 was performed. Infection was the most common postoperative problem. There were seven cases of superficial infection. There was a single case of deep infection requiring intravenous antibiotics and removal of metalwork. Other notable complications were those of secondary osteoarthritis (three cases) and malunion (one case). The key finding of this paper is the 2% incidence of deep infection following the direct operative approach to these fractures. The traditional operative approach to such injuries (initially advocated by Ruedi and Allgower in Injury 2:92-99, 1969) consisted of extensive soft tissue dissection to gain access to the distal tibia. Our preferred method is to access the tibia via the "direct approach" which involves direct access to the fracture site with minimal disturbance of the soft tissue envelope. We therefore believe that open reduction and internal fixation of pilon fractures via the direct approach to be a safe technique in the treatment of such devastating injuries. PMID- 20352432 TI - Biliary cast syndrome and benign biliary stricture as complications of allogeneic hematopoietic stem cell transplantation. PMID- 20352433 TI - Association between acute myeloid leukemia and isochromosome 6p: a case study and review of the literature. PMID- 20352434 TI - Distinct clonal anomalies involving RUNX1 in acute myeloid leukemia at diagnosis and after bone marrow transplantation. PMID- 20352435 TI - Understanding behavioral responses of fish to pheromones in natural freshwater environments. AB - There is an abundance of experimental studies and reviews that describe odorant mediated behaviors of fish in laboratory microcosms, but research in natural field conditions has received considerably less attention. Fish pheromone studies in laboratory settings can be highly productive and allow for controlled experimental designs; however, laboratory tanks and flumes often cannot replicate all the physical, physiological and social contexts associated with natural environments. Field experiments can be a critical step in affirming and enhancing understanding of laboratory discoveries and often implicate the ecological significance of pheromones employed by fishes. When findings from laboratory experiments have been further tested in field environments, often different and sometimes contradictory conclusions are found. Examples include studies of sea lamprey (Petromyzon marinus) mating pheromones and fish alarm substances. Here, we review field research conducted on fish pheromones and alarm substances, highlighting the following topics: (1) contradictory results obtained in laboratory and field experiments, (2) how environmental context and physiological status influences behavior, (3) challenges and constraints of aquatic field research and (4) innovative techniques and experimental designs that advance understanding of fish chemical ecology through field research. PMID- 20352436 TI - Incidence and predictors of atrial fibrillation following transcatheter closure of interatrial septal communications using contemporary devices. AB - BACKGROUND: Transcatheter closure of interatrial septal communications (IASC) is being increasingly performed, while less is known about predictors and incidence of new onset atrial fibrillation (AF) after device closure. Hitherto, most studies have only analyzed some parameters potentially influencing the occurrence of AF, variously omitting others and thus limiting interpretation of results. METHODS: Descriptive, single author, observational study with 68 consecutive patients [aged 53.6 +/- 15.1 years; 32 females (47%)] undergoing IASC closure, being followed up for 16.8 (+/-9.9; 6-42) months. Two patients with AF previous to device implantation had been excluded. Parameters analyzed included age and gender as well as presence of coronary artery disease, hypertension, atrial size, body mass index, device size, and presence of residual shunt. Device size was normalized to maximal disk diameter as declared by the manufacturer. RESULTS: The incidence of new onset AF was 10.3% in the first 6 months after IASC closure. The only two predictors linked to AF were device size (P = 0.002) and, although not reaching significance level, right atrial dilatation (P = 0.08). CONCLUSION: Occluder size was the only significant predictor of post-procedural AF, especially after PFO closure. Although there may be constraints (defect size, presence of an atrial septal aneurysm) that may dictate implantation of a larger device, it is reasonable to implant them "as large as necessary, as small as possible". The influence of atrial dimensions on post-procedural onset of AF must be further investigated. PMID- 20352437 TI - Strain and strain rate echocardiography for evaluation of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. AB - Optimizing the non-invasive imaging of right ventricular (RV) function is of increasing interest for therapy monitoring and risk stratification in patients with idiopathic pulmonary hypertension (IPAH). Therefore, this study evaluated strain and strain rate echocardiography as a tool for comprehensive assessment of RV function and disease severity in IPAH patients. In 30 IPAH patients [WHO functional classes II-IV; mean pulmonary artery pressure (mPAP) 48.8 +/- 12.5 mmHg; pulmonary vascular resistance (PVR) 7.9 +/- 5.3 Wood units] and in 10 matched healthy control subjects' two-dimensional echocardiography, 6-MWD and N terminal pro-brain natriuretic peptide (NT-proBNP) levels were obtained. In IPAH patients when compared with controls, RV systolic strain (-18.8 +/- 4.3 vs. -34.5 +/- 3.8%, p = 0.0016) and strain rate (-1.6 +/- 0.6 vs. -2.7 +/- 0.5 s(-1), p = 0.018) were significantly altered and correlated significantly with elevated NT proBNP levels (r = 0.73 and r = 0.62; p < 0.001, respectively) and reduced 6-MWD (r = -0.76 and r = -0.81; p < 0.001). In IPAH patients, reduced strain correlated with both mPAP (r = 0.61, p = 0.01 for strain; and r = 0.55, p = 0.04 for strain rate, respectively), and PVR (r = 0.84, p < 0.001 for strain; and r = 0.67, p < 0.001 for strain rate, respectively). This study gives first comprehensive evidence that strain echocardiography allows accurate non-invasive assessment of RV function and disease severity in patients with IPAH. PMID- 20352438 TI - Biomechanical evaluation of the dynamic radioulnar convergence after ulnar head resection, two soft tissue stabilization methods of the distal ulna and ulnar head prosthesis implantation. AB - INTRODUCTION: The biomechanical performance of the Darrach procedure, its stabilizing methods and the effectiveness of an ulnar head prosthesis was evaluated in this experiment. PURPOSE: The purpose of this study was to: (1) analyze the dynamic effects of the resection of the distal ulna on radioulnar convergence; and (2) evaluate the mechanical performance of two soft tissue stabilizing procedures (pronator quadratus advancement flap and ECU/FCU tenodesis) for the unstable distal ulnar stump and the implantation of an ulnar head prosthesis (uHead) following a distal ulnar resection (Darrach procedure) on radioulnar convergence. METHOD: With a dynamic PC-controlled forearm simulator, cadaveric forearm rotation was actively and passively performed while simultaneously loading the relevant muscles. The resultant total forearm torque and the three-dimensional kinematics of the ulna, radius and third metacarpal were simultaneously recorded in seven fresh-frozen cadaver upper extremities. RESULTS: The resection of the distal ulna created an extreme instability of the forearm with movement of the radius toward the ulna (0.92-0.38 cm compared to the intact state) in each particular loading condition. The implantation of the ulnar head prosthesis effectively restored the stability of the DRUJ by simulating the geometry of the ulnar head. There were significantly better results after the implantation of the prosthesis compared with the Darrach and the soft tissue stabilization procedures. CONCLUSION: This study provides laboratory validity to the option of implanting an ulnar head endoprosthesis as an attempt to stabilize the distal forearm with instability after Darrach resection in lieu of performing soft tissue stabilization techniques. PMID- 20352439 TI - Real-time monitoring of the Bragg-peak position in ion therapy by means of single photon detection. AB - For real-time monitoring of the longitudinal position of the Bragg-peak during an ion therapy treatment, a novel non-invasive technique has been recently proposed that exploits the detection of prompt gamma-rays issued from nuclear fragmentation. Two series of experiments have been performed at the GANIL and GSI facilities with 95 and 305 MeV/u (12)C(6+) ion beams stopped in PMMA and water phantoms. In both experiments, a clear correlation was obtained between the carbon ion range and the prompt photon profile. Additionally, an extensive study has been performed to investigate whether a prompt neutron component may be correlated with the carbon ion range. No such correlation was found. The present paper demonstrates that a collimated set-up can be used to detect single photons by means of time-of-flight measurements, at those high energies typical for ion therapy. Moreover, the applicability of the technique both at cyclotron and at synchrotron facilities is shown. It is concluded that the detected photon count rates provide sufficiently high statistics to allow real-time control of the longitudinal position of the Bragg-peak under clinical conditions. PMID- 20352440 TI - Factors influencing visual outcome of polypoidal choroidal vasculopathy one year after photodynamic therapy. AB - BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is considered to be a good indication for photodynamic therapy (PDT). We evaluated pre-PDT factors predicting better visual acuity (VA) 1 year after PDT in patients with PCV. METHODS: We evaluated 181 eyes of 181 patients who underwent PDT and were followed up for 1 year. Additional treatments, if needed, were given every 3 months, with a maximum of four PDT sessions, for up to 9 months. We compared best corrected VA (BCVA) 1 year after PDT with that before PDT. Pre-PDT factors favoring better BCVA 1 year after PDT were evaluated using stepwise multiple regression analysis. RESULTS: Mean BCVA improved from 0.29 +/- 0.15 before PDT to 0.43 +/- 0.32 1 year after PDT (p < 0.001). BCVA improved in 55 eyes (30.4%), and was maintained in 110 (60.8%). Pre-PDT factors predicting better BCVA at 1 year were better initial BCVA (beta = 0.271, p < 0.001) within our eligibility criteria up to 0.6, a relatively small diameter of a network of vessels plus polypoidal lesions on indocyanine green angiography (beta = 0.249, p < 0.001), and the absence of a polypoidal lesion under the fovea (beta = 0.175, p = 0.011). CONCLUSION: Better BCVA can be expected 1 year after PDT in eyes with PCV showing better initial BCVA, relatively small lesions on indocyanine green angiography, and no subfoveal polypoidal lesion before PDT. PMID- 20352441 TI - Pigment epithelium derived factor as an anti-inflammatory factor against decrease of glutamine synthetase expression in retinal Muller cells under high glucose conditions. AB - BACKGROUND: The pathogenesis of diabetic retinopathy (DR) is similar to that of a chronic inflammatory disease. A predominant function of Muller cells is to regulate glutamate levels, but in DR the function is compromised. The present study was performed to investigate the role of pigment epithelial derived factor (PEDF) on the expression of glutamine synthetase (GS) in rat retinal Muller cells under high glucose conditions, and to study the possible mechanism for PEDF against decrease of GS expression in retinal Muller cells under high glucose conditions. METHODS: The role of PEDF on the expressions of GS and interleukin 1beta (IL-1beta) in retinal Muller cells under normal and high glucose conditions was measured by western blotting, real-time RT-PCR, or immunocytochemistry. In order to confirm the effect of PEDF on GS against the role of IL-1beta, the PEDF siRNA method was used. RESULTS: High glucose increased the expression of IL 1beta, but decreased the expressions of GS and PEDF in retinal Muller cells. PEDF increased the expression of GS and decreased the expression of IL-1beta in retinal Muller cells under high glucose conditions. The effect of IL-1beta on expression of GS was inhibited by PEDF. Moreover, down-regulation of PEDF expression by siRNA resulted in significantly increasing the expression of IL 1beta, but decreasing the expression of GS in retinal Muller cells. CONCLUSIONS: PEDF increases expression of GS against the effect of IL-1beta in retinal Muller cells under high glucose conditions. These findings suggested that PEDF may act as an anti-inflammatory factor against decrease of GS expression in retinal Muller cells in diabetic retinopathy. PMID- 20352442 TI - Seizures following subconjunctival 5-FU therapy. PMID- 20352443 TI - Intra-examiner repeatability and agreement of corneal pachymetry map measurement by time-domain and Fourier-domain optical coherence tomography. AB - BACKGROUND: To assess the intra-examiner repeatability and agreement of corneal pachymetry maps measured by time-domain (Visante OCT) and Fourier-domain optical coherence tomography (RTVue OCT). METHODS: This observational cross-sectional study enrolled 72 eyes from 72 volunteers. Only one eye of each patient was chosen randomly to receive repeated scanning with both devices by the same examiner, in order to test the intra-observer repeatability. The first scan by each device from all enrolled eyes was used to analyze the difference and agreement between the two devices. The agreement between the two devices was analyzed by the Bland-Altman method. Intra-observer repeatability of each OCT device was analyzed by intra-class correlation (ICC). RESULTS: The mean corneal thickness of the central 2 mm zone was 524.3 +/- 35.7 um and 525.4 +/- 35.3 um by the Visante OCT and the RTVue OCT respectively (p = 0.089). The intra-observer repeatability of the RTVue OCT (ICC = 0.994) was superior to that of the Visante OCT (ICC = 0.989) in the central 2 mm zone. However, the intra-observer repeatability of the RTVue OCT in the pericentral 2 to 5 mm zone was not superior to that of the Visante OCT. Both OCT devices had similar repeatability in the pericentral 2 to 5 mm zone [ICC of the Visante OCT = 0.991; 95% confidence interval (CI) 0.986-0.995), ICC of the RTVue OCT = 0.991; 95% CI 0.985-0.994)). CONCLUSIONS: The difference in CCT measurement by the Visante OCT and the RTVue OCT is probably too small to influence clinical decision making for refractive surgery and glaucoma management. The RTVue OCT demonstrated better intra-observer repeatability in the central 2 mm zone, which probably was related to its rapid image acquisition capability. PMID- 20352444 TI - Response to: Combined treatment of intravitreal bevacizumab and intravitreal triamcinolone in patients with retinal vein occlusion by Schroff et al.. PMID- 20352445 TI - Using multifocal electroretinography hard exudates affect macular function in eyes with diabetic retinopathy. AB - To evaluate the influence of hard exudates on macular function in patients with diabetic retinopathy. METHODS: Thirty seven eyes from 27 diabetic patients, aged 57 +/- 14 years, diabetes duration 12.5 +/- 9 years, not previously treated with photocoagulation, underwent fundus photography, multifocal electroretinography (mfERG) and optical coherence tomography (OCT). Hard exudates were graded from fundus photography with superimposed OCT and a superimposed hexagonal pattern (mfERG) by one retinal specialist, unaware of mfERG and OCT results. We defined three groups; A = eyes with exudates in the analyzed zone, B = eyes with no exudates in the analyzed zone but elsewhere, and C = eyes with no exudates. The mfERG responses and OCT values from five defined areas in the macula were compared. RESULTS: MfERG showed that the implicit time was significantly prolonged in group A compared to group C in the central, middle and outer areas and in the nasal and temporal area (p = 0.045, 0.019, 0.017 and 0.035 and 0.016 respectively), in group B compared to group C in the central area (p = 0.016), and in group A compared to group B in the outer area (p = 0.035). Amplitude differed between group A and C in the middle area and outer area (14.2 +/- 5.2 nV/deg(2) vs 21.1 +/- 8.7 nV/deg(2), p = 0.037 and 14.1 +/- 3.9 nV/deg(2) vs 17.7 +/- 7.1 nV/deg(2) , p = 0.02 respectively), and between group B and C in the temporal area 14.5 +/- 2.2 nV/deg(2) vs 20.0 +/- 8.7 nV/deg(2), p = 0.017). Macular thickness assessed with OCT was similar between the groups. CONCLUSIONS: In eyes with diabetic retinopathy, hard exudates prolong the implicit time assessed with mfERG, compared to eyes without hard exudates, and independently of macular thickness. These results indicate that the hard exudates in the macular region, even at a distance from the fovea centre, have a deleterious effect on macular function. PMID- 20352446 TI - Mutations affecting GABAergic signaling in seizures and epilepsy. AB - The causes of epilepsies and epileptic seizures are multifactorial. Genetic predisposition may contribute in certain types of epilepsies and seizures, whether idiopathic or symptomatic of genetic origin. Although these are not very common, they have offered a unique opportunity to investigate the molecular mechanisms underlying epileptogenesis and ictogenesis. Among the implicated gene mutations, a number of GABAA receptor subunit mutations have been recently identified that contribute to several idiopathic epilepsies, febrile seizures, and rarely to certain types of symptomatic epilepsies, like the severe myoclonic epilepsy of infancy. Deletion of GABAA receptor genes has also been linked to Angelman syndrome. Furthermore, mutations of proteins controlling chloride homeostasis, which indirectly defines the functional consequences of GABAA signaling, have been identified. These include the chloride channel 2 (CLCN2) and the potassium chloride cotransporter KCC3. The pathogenic role of CLCN2 mutations has not been clearly demonstrated and may represent either susceptibility genes or, in certain cases, innocuous polymorphisms. KCC3 mutations have been associated with hereditary motor and sensory polyneuropathy with corpus callosum agenesis (Andermann syndrome) that often manifests with epileptic seizures. This review summarizes the recent progress in the genetic linkages of epilepsies and seizures to the above genes and discusses potential pathogenic mechanisms that contribute to the age, sex, and conditional expression of these seizures in carriers of these mutations. PMID- 20352448 TI - Toxic effects of neem cake extracts on Aedes albopictus (Skuse) larvae. AB - In order to investigate its insecticide potential, the neem cake methanol extract was first analyzed and then separated by different solvents. The high-performance liquid chromatography analysis showed that the neem cake methanol extract still contained relevant quantities of nortriterpenes. Fractions of increasing polarity were obtained from the separation process: hexane fraction (Hp), EtOAc fraction (Ep), n-BuOH fraction (Bp), and aqueous fraction (Wp). The activity of the fractions on Aedes albopictus (Skuse) eggs and larvae was tested, and the Ep fraction exhibits the most relevant larvicide effect. The nuclear magnetic resonance fingerprint analysis of this phytocomplex isolated on EtOAc fraction was performed. The larvicidal effectiveness of the phytocomplex isolated on EtOAc, compared to that of pure and commercial azadirachtin solutions of different concentrations, was checked. The results showed that the activity of the phytocomplex, as a whole, was significantly higher than those of isolated compound solutions. As a consequence, the neem cake is a promising low-cost, easily available on the market, and natural resource to develop a new bioinsecticide, mainly in developing countries. PMID- 20352447 TI - Parasitic contamination in wastewater and sludge samples in Tunisia using three different detection techniques. AB - The limited availability of water results in the reuse of wastewater or sludge. The Tunisian wastewater regulatory guidelines have specific limits for ova of helminths (<1 egg/l) but none for protozoan parasites. We assessed the presence and loads of parasites in 20 samples of raw, treated wastewater and sludge collected from six wastewater treatment plants. Samples were tested by microscopy using the modified Bailenger method (MBM), immunomagnetic separation (IMS) followed by immunofluorescent assay microscopy, and PCR and sequence analysis for the protozoa Cryptosporidium and Giardia. The seven samples of raw wastewater had a high diversity of helminth and protozoa contamination. Giardia spp., Entamoeba histolytica/dispar, Entamoeba coli, Ascaris spp., Enterobius vermicularis, and Taenia saginata were detected by MBM, and protozoan loads were greater than helminth loads. Cryptosporidium and Giardia were also detected by IMS microscopy and PCR. Six of the eight samples of treated wastewater had parasites: helminths (n = 1), Cryptosporidium (n = 1), Giardia (n = 4), and Entamoeba (n = 4). Four of five samples of sludge had microscopically detectable parasites, and all had both Cryptosporidium and Giardia. The genotypes and subtypes of Cryptosporidium and Giardia were of both human and animal origin. These findings suggest that it may be important to monitor the presence of protozoan parasites in treated wastewater and sludge in Tunisia. PMID- 20352449 TI - Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis. AB - We hypothesized that unrecognized differences in epithelial expression of inducible nitric oxide synthase (iNOS), resulting from engineered immunodeficiency, could explain the contradictory findings of prior studies regarding the importance of nitric oxide (NO) in murine models of Cryptosporidium parvum infection. Severe combined immunodeficient mice (SCID) failed to constitutively or inducibly express epithelial iNOS or increase NO synthesis in response to C. parvum infection. In contrast, mice lacking IFN-gamma alone induced both epithelial iNOS expression and NO synthesis in response to infection. Accordingly, lymphocytes mediate epithelial expression of iNOS and NO synthesis independent of IFN-gamma in response to C. parvum infection. These findings in large part explain the contradictory conclusions of prior studies regarding the role of iNOS in C. parvum infection. PMID- 20352450 TI - Some additional data to the occurrence, morphology and validity of Myxobolus turpisrotundus Zhang, 2009 (Myxozoa: Myxosporea). AB - Myxobolus turpisrotundus Zhang, 2009, infects allogynogenetic gibel carp Carassius auratus gibelio (Bloch) and is always regarded as synonymous with Myxobolus rotundus Nemeczek, 1911, since its first report in goldfish Carassius auratus auratus (L.) in China in 1955. In this study, it was comprehensively examined by morphological and molecular biological methods. The round spores of M. turpisrotundus are similar to those of M. rotundus from common bream Abramis brama (L.) in morphology; however, we detected slight differences in morphometry. The ratios of the length and width of the spore to the length and width of the polar capsule of M. turpisrotundus are usually below 2.0 and 1.9, respectively, however these ratios are always above 2.0 and 1.9 in M. rotundus. The plasmodium size of M. turpisrotundus is 600-6,200 microm in diameter and that of M. rotundus is 60-180 microm in diameter. Scanning observation showed the spore surface of M. turpisrotundus was generally pitted. Yet the surface of M. rotundus is smooth. Sequence comparison revealed the small subunit ribosomal RNA gene sequence of M. turpisrotundus did not match any published sequences of M. rotundus (EU710583, 85% over 742 bp; FJ851447, 85% over 742 bp, FJ851448, 85% over 742 bp; FJ851449, 85% over 742 bp). Moreover, phylogenetic analysis showed M. turpisrotundus clustered with the species from allogynogenetic gibel carp with high bootstrap values (100% neighbor-joining, NJ; 100% maximum parsimony, MP) and M. rotundus from common bream composed a new cluster with high bootstrap values (100% NJ, 100% MP). From the morphological and molecular biological data, we gain enough evidences to support the validity of M. turpisrotundus. PMID- 20352451 TI - Furazolidone is a selective in vitro candidate against Leishmania (L.) chagasi: an ultrastructural study. AB - The current treatment for leishmaniasis is unsatisfactory due to toxic side effects, high cost, and problems with drug resistance. Various approaches have been used to identify novel drug candidates to treat Leishmania sp. parasites including the use of re-purposed drugs. Furazolidone is a nitrofuran derivative with antiprotozoal and antibacterial activity and is used for the treatment of giardiasis. In the present work, we determined the in vitro antileishmanial activity of furazolidone and its ability to induce ultrastructural alterations of parasites. Promastigotes of Leishmania (L.) chagasi, Leishmania (V.) braziliensis, Leishmania (L.) major, and Leishmania (L.) amazonensis were highly susceptible to furazolidone, with IC(50) values ranging between 0.47 and 0.73 microg/mL. Furazolidone was also very effective against L. chagasi intracellular amastigotes, and despite mammalian cytotoxicity, the selectivity index was 8.0 in human monocytes. The drug also had limited toxicity in mice erythrocytes. Furazolidone demonstrated specific activity against Leishmania, a potential consequence of the lack of macrophage nitric oxide activation. As determined by electron transmission microscopy, drug treatment induced severe damage to the parasite mitochondria and nucleus. This older oral drug is an effective agent for the treatment of L. (L.) chagasi in vitro and is a novel candidate for further experimental studies. PMID- 20352452 TI - Spermatological characters of the spathebothriidean tapeworm Didymobothrium rudolphii (Monticelli, 1890). AB - Spermiogenesis and the spermatozoon ultrastructure of the adult Didymobothrium rudolphii (Spathebothriidea) have been examined using transmission electron microscopy for the first time. The dense material is present in the apical region of the differentiation zone in the early stage of spermiogenesis, similarly as in other basal tapeworms examined to date. The orthogonal development of the two flagella is followed by a flagellar rotation and their proximodistal fusion with the median cytoplasmic process (MCP). The two pairs of electron-dense attachment zones in the MCP mark the lines where the proximodistal fusion of MCP with two axonemes takes place. D. rudolphii exhibits polymorphism of the intercentriolar body during spermiogenesis. The mature spermatozoon possesses the two axonemes of 9 + "1" trepaxonematan pattern, nucleus, cortical microtubules (CMs), and electron-dense granules. The anterior extremity of the gamete lacks a crested body and exhibits a centriole surrounded by a semiarc of electron-dense tubular structures. The two parallel rows of the CMs have been found in the proximal part of the two-axoneme region of the spermatozoon for the first time in the Eucestoda. The posterior extremity of the gamete exhibits pattern of the disorganized axoneme. The ultrastructural features of the sperm/spermiogenesis support a view about the close relationships of the Spathebothriidea and Diphyllobothriidea and the basal position of the Spathebothriidea within the Eucestoda. PMID- 20352453 TI - A survey of Neospora caninum-associated bovine abortion in large dairy farms of Mashhad, Iran. AB - Neospora caninum is an apicomplexan protozoon causing abortion in cattle worldwide. The present study was designed to assess the importance of this parasite for causing abortion in dairy farms in the Mashhad area of Iran. Of the aborted bovine fetuses, 151 were collected from dairy farms between 2006 and 2008. First, brain samples were examined by polymerase chain reaction (PCR) for the presence of N. caninum DNA, diagnosis was complemented with immunohistochemistry (IHC) and fetal serology (ELISA). Twenty-two (14.5%) of bovine fetuses were considered to be infected with N. caninum with at least one diagnostic technique being positive. PCR yielded 18 (11.9%) positive out of 151 brain samples. Only 52 brain samples were suitable for IHC examination, and N. caninum organism was detected in six (11.5%) of these 52 brain samples. Fetal fluids (n = 151) were assessed with a N. caninum-ELISA, resulting in 15 (9.9%) seropositive fetal fluids samples. In the present study, a good agreement was observed between PCR and ELISA, and a fair agreement between PCR and IHC. The results indicated that abortion due to N. caninum infection is prevalent among large-size dairy farms in the Mashhad area of Iran, and that different complementary diagnostic techniques should be used to increase the chance to detect N. caninum. PMID- 20352454 TI - Food-borne trematode infections of humans in the United States of America. AB - This review examines the literature on imported (allochthonous) and local (autochthonous) cases of food-borne trematode (FBT) infections in the United States of America (USA) from 1890 to 2009. Most of the literature is concerned with imported cases of the opisthorchiids Clonorchis sinensis and Opisthorchis viverrini. These flukes cause serious pathology in the liver and biliary system of humans. Chronic cases may induce liver (hepatocarcinoma) and bile duct (cholangiocarcinoma) cancers in humans. Clonorchiasis and opithorchiasis are preventable diseases that can be avoided by eating properly cooked freshwater fish products. Several species of lung flukes in the genus Paragonimus are local or imported FBT in the USA. The endemic cycle occurs in the USA with various local snails and crustaceans serving as intermediate hosts. Paragonimids are acquired when humans eat raw or improperly cooked freshwater crustaceans containing metacercarial cysts. Infection can cause severe lung disease and the symptoms of paragonimiasis often mimic those of tuberculosis and other non helminthic diseases. Paragonimiasis can be avoided by not eating raw or improperly cooked shellfish. The liver fluke Fasciola hepatica can be acquired by eating raw or uncooked vegetation. The cycle exists in the USA involving local snails and aquatic vegetation. Although some cases are local, most are imported by travelers or immigrants. Fascioliasis can cause serious liver and biliary diseases in humans and consumption of tainted vegetation should be avoided. Lesser known FBT have been reported in the USA including species of Alaria, echinostomids, heterophyids, troglotrematids, and a self-induced infection of Plagiorchis. Treatment of the FBT mentioned in this review consists of various regimens of praziquantel, except for F. hepatica where the drug of choice is triclabendazole. PMID- 20352455 TI - Aortic stiffness in ESRD children before and after renal transplantation. AB - Cardiovascular complications are the main cause of death in end-stage renal failure in adult patients, but those complications start in childhood. Renal transplantation (RT) seems to reduce or even reverse certain abnormalities seen in dialyzed patients. Since RT seems to correct metabolic abnormalities that play a role in cardiovascular disease, aortic pulse wave velocity (APWV) was used to evaluate aortic stiffness before and after RT. We included 15 children on chronic hemodialysis (HD), aged 11.1 +/- 4.8 years and dialysis duration was 12.9 +/- 7.4 months. APWV was performed every 6 months before RT and 6 months after. There was no significant difference in APWV (6.1 +/- 1.3 m/s vs 6.5 +/- 1.4 m/s) and augmentation index (AI) on HD and 6 months after RT. APWV pre-transplant was not correlated with time on HD, but increased with age (p = 0.016). No correlation between APWV pre-/post-transplant and other HD parameters or calcineurin inhibitor exposure were found. Only graft function was inversely correlated with APWV post-transplant (p = 0.02). In conclusion, aortic stiffness seems to remain stable before and 6 months after pediatric RT. Graft function was inversely correlated with APWV. Differences in vessel structure among children of the same age group and increase in aortic stiffness with age may jeopardize data interpretation. PMID- 20352456 TI - A conceptual framework for the molecular pathogenesis of progressive kidney disease. AB - The data regarding the pathogenesis of progressive kidney disease implicate cytokine effects, physiological factors, and myriad examples of relatively nonspecific cellular dysfunction. The sheer volume of information being generated on this topic threatens to overwhelm our efforts to understand progression in chronic kidney disease or to derive rational strategies to treat it. Here, a conceptual framework is offered for organizing and considering these data. Disease is initiated by an injury that evokes a tissue-specific cellular response. Subsequent structural repair may be effective, or the new structure may be sufficiently changed that it requires an adaptive physiological response. If this adaptation is not successful, subsequent cycles of misdirected repair or maladaptation may lead to progressive nephron loss. To illustrate how this framework can be used to organize our approach to disease pathogenesis, the role of cytokines in proteinuria and progressive glomerular disease is discussed. Finally, this theoretical framework is reconsidered to examine its implications for the diagnosis and treatment of clinical conditions. Application of this schema could have significant relevance to both research inquiry and clinical practice. PMID- 20352457 TI - Analysis of CTNS gene transcripts in nephropathic cystinosis. AB - Nephropathic cystinosis (NC) is an autosomal recessive disorder caused by mutations of the CTNS gene that encodes for a cystine transmembrane transporter. Several mutations have been described in the coding and promoter regions of the CTNS gene in affected individuals. We selected three patients with NC from two unrelated families, in whom sequence analysis of the CTNS gene detected only one or no mutations. Total RNA was isolated from peripheral blood mononuclear cells or fibroblasts and CTNS transcripts were analyzed. We observed a skipping of exon 5 (85 bp) in two siblings and an intron 9 retention of 75 bp associated with partial replication of exon 9 in the third patient. Genomic DNA analysis of intron regions surrounding exon 5 showed a point mutation in the hypothetical lariat branch site of intron 4 at position -24 (c.141-24 T > C) in the first two patients and a duplication of 266 bp including a part of exon and intron 9 in the third patient. Analysis of CTNS gene transcripts allowed identification of mutations in patients in whom CTNS mutations could not be detected by traditional DNA sequencing. These results support the hypothesis that cystinosis is a monogenic disorder. PMID- 20352460 TI - Mitomycin C modulates DNA-double strand break repair genes in cervical carcinoma cells. AB - In a previous study, we elucidated the apoptotic mechanism mediated via Fas/FasL dependent pathway in mitomycin C-treated cervical carcinoma cells. In this study, 2-D and MALDI-TOF analyses were performed in order to search mitomycin C-induced modulators in cervical carcinoma cells. Some protein spots down- or up-regulated by mitomycin C were separately selected from the 2-D gels. Twenty protein spots were identified from the 2-D gels. Among the 20 spots, 11 spots were down regulated, whereas 9 spots were up-regulated in SiHa/pRSV-luc cells by mitomycin C. Three spots have not been identified in the database. Ku70-binding protein (KUB3), MHC class I antigen, MHC class I chain-related protein A or multi-PDZ domain protein 1, MAGUK P55 subfamily member 3 or lamda/iota protein kinase C interacting protein, and GL014 or Sad1/unc-84 protein-like 1 were suppressed by mitomycin C treatment. Heat shock 60 kDa protein 1 (chaperonin), similar to heat shock protein 90 kDa protein alpha or nine in centrosomal protein isoform C, NADP dependent malic enzyme, mitochondrial precursor, GRB10 adaptor protein, glycogenin-interacting protein 1, cystathionine gamma-lyase, G2/mitotic-specific cyclin B2 or heat shock 90 kDa protein 1 alpha, peptidyl-prolyl cis-trans isomerase B, and PARP-2 (fragment) were induced by mitomycin C. KUB3, Brca1, and E6 gene expressions were down-regulated by mitomycin C in HPV-positive cervical cancer cells, SiHa/pRSV-luc and SiHa. In these studies, we suggest that MMC down regulated the expression levels of the upstream molecules of DNA-double strand break repair system, non-homologous end joining or homologous recombination, resulting in the suppression of cervical cancer cell growth. PMID- 20352458 TI - When to initiate ACEI/ARB therapy in patients with type 1 and 2 diabetes. AB - Angiotensin converting enzyme inhibitors (ACEI) and angiotensin 2 receptor blockers (ARB) have become a mainstay of adjunctive therapy for the prevention and amelioration of diabetic nephropathy. Although ACEI were shown over 20 years ago to slow the rate of loss of renal function in diabetic subjects with decreased renal function, the question of how early in the course of diabetes to introduce them remains unresolved. Recent studies suggest that very early initiation of ACEI/ARB therapy may not have demonstrable beneficial effects even over a period of years. PMID- 20352461 TI - Peptidomic analysis of the skin secretions of the frog Pachymedusa dacnicolor. AB - High-resolution mass spectrometry-based peptidomics has been used to characterize several components in electro-stimulated skin secretions of the endemic Mexican frog Pachymedusa dacnicolor. Peptide mass screening performed in an Orbitrap-XL mass spectrometer showed that P. dacnicolor skin secretions possess 194 different components with molecular masses ranging mainly from 500 to 6,000 Da. Dozens of molecules were partially sequenced including two novel protease inhibitors. Additionally, one posttranslationally modified bradykinin and two novel dermaseptin-like antimicrobial peptides were fully sequenced. The novel peptide named here DMS-DA5 was fully characterized and showed potent antibacterial activity against various bacteria such as Escherichia coli, Bacillus subtilis, Salmonella enterica serovar typhimurium, and Pseudomonas aeruginosa with minimal inhibitory concentrations from 3.10 to 25.0 microM. PMID- 20352459 TI - Heat shock protein 70 induction and its urinary excretion in a model of acetaminophen nephrotoxicity. AB - Acetaminophen (APAP) is an analgesic-antipyretic drug widely used in children. In the present study, we used an in vivo model of APAP-induced nephrotoxicity in male Wistar rats. We analyzed whether toxic doses of APAP could induce heat shock protein 70 (HSP70) in the kidney and whether HSP70 could be detected in urine. Renal function and histological evaluation of the kidneys were performed at different times after APAP administration (1,000 mg/kg body weight i.p.). Cellular injury was assessed by Triton X-100 solubilization of Na(+)/K(+) ATPase. Renal and hepatic glutathione levels were also measured. Urinary N-acetyl-beta-D glucosaminidase (NAG) excretion increased 4 h after intoxication. At this time, urea and creatinine were at control levels and a slight degree of histological alteration was detected. Kidney microscopic evaluation, Na(+)/K(+) ATPase solubility, creatinine, and urea levels and NAG excretion did not differ from those of controls 48 h after APAP administration. HSP70 was detected in urine obtained from 4 to 24 h after APAP administration. HSP70 abundance in renal cortex was increased at early time points and 48 h after APAP administration. Urinary HSP70 excretion would be a marker of its renal induction combined with the loss of tubule integrity. NAG would be a suitable early biomarker of APAP induced nephrotoxicity. PMID- 20352462 TI - Synthesis and characterization of novel, optically active polyamides derived from S-valine natural amino acid and bulky anthracenic side chain. AB - This is the first description of the application of molten tetrabutylammonium bromide (TBAB) in the presence of triphenyl phosphite (TPP) for the synthesis of novel polyamides (PAs). Monomer diacid, 5-[(9,10-dihydro-9,10-ethanoanthracene 11,12-dicarboximido)-3-methylbutanoylamino]isophthalic acid (4), having anthracenic and amino acid S-valine pendant group, was synthesized in four steps. Several novel, optically active PAs were prepared by the condensation of synthesized diacid monomer 4 with various aromatic diamines using two different techniques: a mixture of N-methyl-2-pyrrolidone (NMP)/TPP/pyridine/calcium chloride (method I) and combination of TPP with TBAB (method II). The main goal of the present paper was to prepare novel PAs in a green media by removal of toxic reagents. Therefore, TBAB/TPP was used as a novel, easy, safe and eco friendly method for the preparation of aromatic PAs. This method is compared with the polymerization reaction under conventional solvent and in the case of TBAB as a new method, higher yields, inherent viscosities and thermally stable of PAs are gained. The resulting polymers showed good solubility in polar aprotic solvents such as dimethyl sulfoxide, NMP, N,N-dimethylacetamide and N,N-dimethylformamide. These polymers are characterized with respect to chemical structure and purity by means of specific rotation experiments, FT-IR, 1H NMR spectroscopy techniques and elemental analysis. The obtained PAs exhibit good thermal stability up to 335 degrees C for 10% weight loss in nitrogen atmosphere and glass transition temperatures fell in the rang of 177-185 degrees C. PMID- 20352463 TI - Hydrogen sulfide protects against vascular remodeling from endothelial damage. AB - Remodeling by its very nature implied synthesis and degradation of extracellular matrix (ECM) proteins. Although oxidative stress, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) have been implicated in vascular remodeling, the differential role of MMPs versus TIMPs and oxidative stress in vascular remodeling was unclear. TIMP-3 induced vascular cell apoptosis, therefore, we hypothesized that during vascular injury TIMP-3, MMP-9 and -12 (elastin-degrading MMP) were increased, whereas MMP-2 (constitutive MMP) and TIMP 4 (cardioprotective TIMP) decreased. Because of the potent anti-oxidant, vasorelaxing, anti-hypertensive agent, hydrogen sulfide (H2S) was used to mitigate the vascular remodeling due to the differential expression of MMP and TIMP. Carotid artery injury was created by inserting a PE-10 catheter and rotating several times before pulling out. The insertion hole was sealed. Mice were grouped: wild type (WT), wild-type damaged artery (WTD), WT+NaHS (sodium hydrogen sulfide, precursor of H2S) treatment (30 umol/L in drinking water/6 weeks) and WTD+NaHS treatment. Carotid arteries were analyzed for oxidative stress and remodeling, by measuring super oxide dismutase-1 (SOD1), p47 (NADPH oxidase subunit), nitrotyrosine, MMPs and TIMPs by in situ immunolabeling and by Western blot analyses. The results suggested robust increase in p47, nitrotyrosine, MMP-9, MMP-12, TIMP-3 and decrease in SOD1 and MMP-2 levels in the injured arteries. The treatment with H2S ameliorated these effects. We concluded that p47, TIMP-3, MMP-9 and -12 were increased where as SOD-1, MMP-2 and TIMP-4 were decreased in the injured arteries. The treatment with H2S mitigated the vascular remodeling by normalizing the levels of redox stress, MMPs and TIMPs. PMID- 20352464 TI - Gemcitabine and cisplatin chemotherapy induced reversible posterior leukoencephalopathy syndrome in a bladder cancer patient. AB - Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinical entity, the common clinical symptoms of which are headache, disturbance of consciousness, altered mental status, seizures, and visual disturbance. Recently, some cases have been reported in association with the increased use of cytotoxic and immunosuppressive agents in cancer patients, and relevant reports have increased with advances in radiological examinations. We describe here the case of a 50-year-old man with advanced bladder cancer who suddenly experienced diminished spontaneity and speech, and finally became semicomatose. Two months previously, he had received gemcitabine and cisplatin chemotherapy. Computed tomography and magnetic resonance imaging revealed symmetrical edema of the posterior occipital lobe and thalamus. Based on these findings, we made a diagnosis of RPLS and treated him with supportive measures. His mental status gradually improved in 2 weeks, although slight neurological symptoms persisted. When the level of consciousness of a cancer patient worsens rapidly, this syndrome should be included in the differential diagnosis and recognized at an early stage. Early supportive management and discontinuation of the causative medication may reverse the clinical and radiological manifestations of the syndrome. PMID- 20352465 TI - Use of musculoskeletal ultrasound in Japan: a survey of practicing rheumatologists. AB - We aimed to describe how often Japanese rheumatologists currently use musculoskeletal ultrasound (MSUS), and how they are currently being trained in the use of this imaging technique. Questionnaires were sent to 200 Japanese rheumatologists: 100 to participants attending the first Scientific Meeting of the Japanese Society of Imaging in Rheumatic Diseases in 2006, and 100 to other randomly selected rheumatologists certified by the Japan College of Rheumatology. A total of 139 questionnaires (74 from meeting participants, 65 from randomly selected rheumatologists) were completed and analyzed. Twenty-four of the 74 respondents (32.4%) in the meeting participants group used MSUS imaging for patient management, while only 7 of the 65 respondents (10.8%) in the certified rheumatologists group used MSUS imaging for patient management. Sixty-five of the 74 respondents (87.8%) in the meeting participants group and 54 of the 65 respondents (83.1%) in the certified rheumatologists group considered MSUS to be a useful tool. Only a minority of respondents used MSUS in the management of their patients. Lack of training in MSUS was the principal reason for not performing MSUS. Japanese rheumatologists would prefer future training in the form of intensive courses and training sessions. PMID- 20352466 TI - Protracted febrile myalgia syndrome in familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is an autosomal, recessively inherited multisystem disease that affects various groups of people originating from the Mediterranean Sea region, most specifically those of Jewish, Turkish, Armenian, and Arabic ethnicity. Recurrent attacks of fever and sterile polyserositis of the peritoneum, synovial membranes, and pleura are the main clinical features, although the clinical features of FMF have been expanded in recent years to also include severe myalgia, scrotal swelling, cardiac involvement, and protracted febrile myalgia syndrome (PFMS). PFMS is seen in only a small percentage of FMF patients and is characterized by severe debilitating myalgia of the upper and lower extremities and high fever, occasionally accompanied by abdominal pain, diarrhea, arthritis/arthralgia, and transient vasculitic purpura mimicking Henoch Schonlein purpura (HSP). Here, we report on a patient with FMF who also presents with PFMS, which is an uncommon and severe manifestation of the disease. PMID- 20352467 TI - Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells? AB - By counteracting the shortening of chromosome telomeres, telomerase reverse transcriptase (hTERT) prevents senescence and age-related cell death. Embryonic cells display a high telomerase activity that declines rapidly with cell differentiation. Conversely, de-differentiated tumor cells tend to re-express telomerase. In view of the controversial data on the reciprocal correlation between cell proliferation and differentiation, we questioned whether telomerase overexpression and the resulting immortalization would affect the functional phenotype of human endothelial cells. Our comparative analysis addressed (1) distinct cell adhesion to different ECM-proteins analyzed on miniaturized multisubstrate arrays (MSA), (2) protein expression of diverse markers, (3) the uptake of DiI-Ac-LDL, (4) the inflammatory response based on upregulation of ICAM 1, (5) tube formation, and (6) the barrier properties of cell monolayers in transfilter cultures. Our results, based on some 40 data sets, demonstrate that immortalization of primary endothelial cells by hTERT maintains the typical endothelial characteristics without any sign of functional de-differentiation. PMID- 20352468 TI - Transcription factor-based modulation of neural stem cell differentiation using direct protein transduction. AB - In contrast to conventional gene transfer strategies, the direct introduction of recombinant proteins into cells bypasses the risk of insertional mutagenesis and offers an alternative to genetic intervention. Here, we explore whether protein transduction of the gliogenic transcription factor Nkx2.2 can be used to promote oligodendroglial differentiation of mouse embryonic stem cell (ESC)-derived neural stem cells (NSC). To that end, a recombinant cell-permeant form of Nkx2.2 protein was generated. Exposure of ESC-derived NSC to the recombinant protein and initiation of differentiation resulted in a two-fold increase in the number of oligodendrocytes. Furthermore, Nkx2.2-transduced cells exhibited a more mature oligodendroglial phenotype. Comparative viral gene transfer studies showed that the biological effect of Nkx2.2 protein transduction is comparable to that obtained by lentiviral transduction. The results of this proof-of-concept study depict direct intracellular delivery of transcription factors as alternative modality to control lineage differentiation in NSC cultures without genetic modification. PMID- 20352470 TI - Primary disseminated central neurocytoma: cytological and MRI evidence of tumor spread prior to surgery. AB - Since its description in 1982, central neurocytoma (CN) has been a relatively innocuous rare tumor of the central nervous system. Comprising of less than 0.5% of all intracranial tumors, most are reported to be slow growing, with low recurrence rates, and a favorable prognosis. Because of its rarity, its cellular biology, prognosis, and treatment strategies are difficult to ascertain. Its low grade nature allows for continued growth before signs and symptoms of increase intracranial pressures ensue. Some authors theorize CN may derive from bipotential precursor cells of the periventricular germinal matrix, which are capable of both neuronal and glial differentiation, but maintain a low proliferative potential after birth. Several retrospective studies indicate that a MIB-1 index of greater than 2-3% will show a recurrence rate of 48-63%, respectively. Of hundreds of cases reported, the incidence of recurrence is very low, which makes aggressive forms of this tumor difficult to study. There are only 12 cases of craniospinal dissemination reported since its inception. The diagnoses of dissemination in these cases are made only after surgical intervention. We report the only case of primary disseminated CN, diagnosed on radiographic studies, and confirmed by cytology of the cerebral spinal fluid, prior to any kind of intervention. These cases may represent a subgroup of a more aggressive CN, which requires more assertive surveillance including CSF sampling and routine imaging of the neuroaxis. PMID- 20352469 TI - Loss of CD24 expression promotes ductal branching in the murine mammary gland. AB - CD24 is expressed on mammary stem cells and is used as a marker for their isolation, yet its function in the mammary gland still needs to be examined. Here we show that CD24 is expressed throughout the luminal epithelial cell layer, but only weakly in myoepithelial cells. During lactation, CD24 expression was suppressed within alveoli, but upregulated post-lactation, returning to a pre pregnant spatial distribution. CD24-deficient mice exhibited an accelerated mammary gland ductal extension during puberty and an enhanced branching morphogenesis, resulting in increased furcation in the ductal structure. CD24-/- mammary epithelial cells were able to completely repopulate cleared mammary fat pads and to give rise to fully functional mammary glands. Together, these data suggest that while CD24 is expressed in mammary epithelium compartments thought to contain stem cells, CD24 is not a major regulator of mammary stem/progenitor cell function, but rather plays a role in governing branching morphogenesis. PMID- 20352471 TI - Low-dose fotemustine for recurrent malignant glioma: a multicenter phase II study. AB - Fotemustine at the conventional dose of 100 mg/m(2) is an active treatment for recurrent malignant gliomas (RMGs). However, it is associated with a relevant incidence of severe myelotoxicity, which is not justified in the palliative setting of this disease. This study was conducted to address whether administration of fotemustine at 60 mg/m(2) (induction) followed by 75 mg/m(2) (maintenance) would preserve clinical activity with the advantage of improved tolerance. Forty patients with RMGs pretreated with <=2 lines of chemotherapy were enrolled. Median age was 57 years (26-80) and median Karnofsky performance status was 80 (60-100). Thirty-one patients (77.5%) had tissue available for analysis of the O(6)-methylguanine methyltransferase (MGMT) gene promoter which was found to be methylated in 14 cases (45%). Overall, 8 partial responses (20%) and 13 disease stabilizations (32.5%) were observed for a disease-control rate of 52.5%. At 6 months, 21% of patients were free from progression. Grades 3 and 4 platelet and white blood cell toxicity occurred in <=10% of patients, and no patients discontinued treatment because of toxicity. No significant difference was observed for disease control rate between methylated and unmethylated patients, although a trend toward improved progression-free survival was reported for methylated patients. Low-dose fotemustine has activity comparable with that of the full-dose regimen, therefore it should be preferred for its greater tolerability. The role of MGMT gene promoter methylation status in relation to sensitivity to fotemustine is still unclear and needs further evaluation in future clinical trials. PMID- 20352472 TI - Treatment-induced leukoencephalopathy in primary CNS lymphoma presenting as lower body parkinsonism. PMID- 20352473 TI - Natural history and management of low-grade glioma in NF-1 children. AB - Pediatric neurofibromatosis type 1 (NF-1) patients are prone to developing low grade glioma (LGG). The HIT-LGG study 1996 aimed to observe the natural history of pediatric LGG and to postpone irradiation in younger children by using carboplatinum and vincristine in case non-surgical treatment was required. A total of 109 of 1,044 (10.4%) protocol patients had a genetic NF-1 trait [57 female patients; median age 5.1 years (range 1-15.4 years)]. Eighty-three patients (76%) suffered from an optic pathway tumor. Neuroimaging only allowed diagnosis in 67 patients. Histology revealed pilocytic astrocytoma WHO grade I in 38 of 42 biopsied patients. Sixty-five (60%) patients received non-surgical treatment, either chemotherapy (n = 55) or irradiation (n = 10). The overall survival rate of 96% after a median observation time of 5.25 years contrasts with an event free survival rate (EFS) of 0.24 at 5 years. Progressive LGG were observed even in children older than 11 years. Chiasmatic/postchiasmatic localization was a univariate risk factor for progressive disease. In the chemotherapy group, we observed a 5-year progression-free survival (PFS) rate of 0.73. Similarly, the PFS rate in the irradiation group was 0.78. Multivariate analysis revealed surgical intervention and localization within the optic pathway as factors that increased the risk of tumor progression. In this large prospective multinational study, LGG in NF-1 patients did progress in 75% of patients. Chemotherapy yielded acceptable PFS. The biological factors determining progression remain poorly understood. PMID- 20352474 TI - Spontaneous skin damage and delayed wound healing in SOD1-deficient mice. AB - Superoxide dismutase 1 (SOD1) is an important antioxidative enzyme that protects skin from oxidative stress. SOD1 (-/-) mice with a genetic background of b129Sv mice showed facial skin damage after 15 weeks of age. Eyelid swelling occurred as the initial symptom and caused impairment by triggering self-scratching. The period required for wound healing in the back was markedly delayed in 20-week SOD1 (-/-) mice. Oxidative stress markers, 4-hydroxynonenal and thiobarbituric acid-reactive substances, were unexpectedly lower in SOD1 (-/-) mice at day 1 after wounding. The decay rate of electron paramagnetic resonance signal intensity of intravenously injected nitroxide radical indicated that the half life of the signal intensity was significantly prolonged in the wounded skin of SOD1 (+/+) mice. However, while the half-life of the signal intensity in control skin was a little longer in SOD1 (-/-) mice, it did not change in wounded skin. Taken together, these data suggest that the skin of SOD1 (-/-) mice is in redox imbalance and prone to damage by wounding. PMID- 20352475 TI - Cytochrome c redox state influences the binding and release of cytochrome c in model membranes and in brain mitochondria. AB - Cytochrome c (cyt c), a component of the respiratory chain, promotes apoptosis when released into the cytosol. Cyt c anchorage within mitochondria depends on cardiolipin (CL). Detachment and release have been related to CL loss and peroxidation. We report that NaN(3)-dependent complex IV inhibition, accompanied by impairment of respiration, resulted in cyt c release. Contrarily, inhibition of respiration upstream cyt c with complex I and III inhibitors was not accompanied by the release of the protein, despite CL decrease and monolyso-CL increase. No CL changes and H(2)O(2) formation were observed by inhibiting complex IV. In cyt c-CL liposomes, breaching cyt c-CL hydrophilic interactions produced a higher release of the reduced, compared to the oxidized form, suggesting that the hydrophobic component of cyt c-CL binding is prevalent in the oxidized form. Free or liposome-reconstituted cyt c was able to form fatty acid protein complexes (palmitate < linoleate < oleate) only in its reduced form. We hypothesize that reduced cyt c-fatty acid binding favors the dislocation of the protein from anchoring CL. A mechanism for cyt c release independent of CL peroxidation by H(2)O(2) is feasible. It could weaken the hydrophobic component of cyt c-CL interactions and might function following complex IV inhibition or in oxygen lack, both conditions producing accumulation of reduced cyt c and free fatty acids. PMID- 20352476 TI - Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats. AB - In this study, we investigated the oxidative stress influence in some prosurvival and proapoptotic proteins after myocardial infarction (MI). Male Wistar rats were divided in two groups: Sham-operated (control) and MI. MI was induced by left coronary artery occlusion. 28-days after surgery, echocardiographic, morphometric, and hemodynamic parameters were evaluated. Redox status (reduced to oxidized glutathione ratio, GSH/GSSG) and hydrogen peroxide levels (H(2)O(2)) were measured in heart tissue. The p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK 3beta/GSK-3beta ratios, as well as apoptosis-inducing factor (AIF) myocardial protein expression were quantified by Western blot. MI group showed an increase in cardiac hypertrophy (23%) associated with a decrease in ejection fraction (38%) and increase in left ventricular end-diastolic pressure (82%) when compared to control, characterizing ventricular dysfunction. Redox status imbalance was seen in MI animals, as evidenced by the decrease in the GSH/GSSG ratio (30%) and increased levels of H(2)O(2) (45%). This group also showed an increase in the ERK phosphorylation and a reduction of Akt and mTOR phosphorylation when compared to control. Moreover, we showed a reduction in the GSK-3beta phosphorylation and an increase in AIF protein expression in MI group. Taken together, our results show increased H(2)O(2) levels and cellular redox imbalance associated to a higher p ERK and AIF immunocontent, which would contribute to a maladaptive hypertrophy phenotype. PMID- 20352477 TI - What variables are associated with an expressed wish to kill a doctor in community and injured patient samples? AB - Working in a health care setting has been identified as a primary risk factor for violent assault, which is often perpetrated by patients. Patient dangerousness is a multidimensional phenomenon, which may include violent ideation, homicidal planning, a history of violent acts, or overt threatening behavior. Although the verbal report of thoughts of killing a doctor is only one of many risk factors for patient dangerousness, reports of homicidal ideation are widely regarded as being sufficient to warrant concern, and to indicate a need for further assessment of the patient. In this study, 2264 subjects (1329 healthy community subjects, 158 non-healthy community subjects, and 777 rehabilitation patients) were asked if they had a desire to kill a doctor that they had seen. Subjects responding positively to this item were compared to subjects responding negatively to the item using all available demographic variables and BHI 2 scales using chi-square or t-test. Significant variables (p<.01) were then utilized in a logistic regression to generate a model for this wish. Three variables significantly predicted this wish: the Doctor Dissatisfaction (p<.001) and Borderline (p<.001) scales of the BHI 2, and injury-related litigation status (p=.002). The presence of one of these variables, especially Doctor Dissatisfaction, should prompt a more thorough assessment of potential danger to healthcare workers. PMID- 20352478 TI - Community health workers' support for cancer clinical trials: description and explanation. AB - Ethnic differences in participation in cancer clinical trials slow advances in medical knowledge that can reduce health care disparities. Community health workers (CHWs) are an increasingly important bridge between the health care system and underserved communities and could play an important role in increasing rates of clinical trial participation. We investigated community health workers' orientations to medical research and cancer clinical trials with a mixed methods design: two focus groups, 11 intensive interviews, and a structured survey of 76 CHW training workshop participants. CHWs demonstrated high levels of commitment to improving the health of community members but considerable distrust of researchers' motives, low levels of knowledge about cancer clinical trials, and frequent perceptions of bias in the health care system. Support for research is associated with more research experience, self-assessed knowledge, and Hispanic ethnicity, but with less seniority as a CHW. Neither actual knowledge of cancer clinical trials nor perceptions of bias in the health care system were related to degree of support for medical research. Community health workers perceive bias in the health care system but recognize the importance of medical research and are interested in learning more about cancer clinical trials. Research experience increases support for medical research; education increases perceptions of health care system bias. PMID- 20352479 TI - Pediatric obesity community programs: barriers & facilitators toward sustainability. AB - Our current generation of young people could become the first generation to live shorter lives than their parents. Families need resources in their community to address this issue. Identifying barriers and facilitators of community organizations to offer obesity-related services is a first step in understanding sustainable community programs. The objective of this study is to identify common barriers and facilitators in community organizational programs designed to prevent or reduce pediatric obesity. We conducted an exploratory qualitative research study based on grounded theory. Thirty-six community organizations were identified based on self-descriptions of goals involving pediatric obesity. Semi structured, systematic, face-to-face interviews among program directors (n = 24) were recorded, transcribed, and coded for recurrent themes. Relevant themes were abstracted from interviews by a standardized iterative process by two independent reviewers between December 2007 and November 2008. Theme discordance was reconciled by a third reviewer. Seventy percent of organizations indicated that obesity prevention/treatment was their explicit goal with remaining groups indicating healthy lifestyles as a more general goal. Facilitators to provision of these programs included: programmatic enhancements such as improved curriculums (73%), community involvement such as volunteers (62.5%), and partnerships with other programs (54.2%). Barriers that threatened sustainability included lack of consistent funding (43.8%), lack of consistent participation from the target population (41.7%) and lack of support staff (20.8%). New approaches in fostering partnerships between organizations need to be developed. Building coalitions and engaging community members in developing community based programs may be a helpful strategy to strengthen community-based programs to address the pediatric obesity epidemic. PMID- 20352480 TI - Media attention and public perceptions of cancer and eastern equine encephalitis. AB - Previous research has found that members of the public have a skewed sense of health risk. The purpose of this research was to investigate how mass media use influences perceptions of threat from cancer and eastern equine encephalitis (EEE). Investigators performed a media content analysis of 253 health-related articles from 11 Massachusetts newspapers, then used logistic regression to analyze responses to a health communication survey of 613 Massachusetts adults. A greater proportion of cancer articles compared to those about EEE mentioned progress in combating the disease (61.0% vs. 16.2%, P < 0.0001), while a greater proportion of EEE articles mentioned new incidents of illness (35.4%, vs. 4.6% P < 0.0001). Over half of all respondents perceived EEE as an equal or greater threat than cancer. Paying a lot of attention to health media was related to higher odds of perceiving EEE as a threat (OR 2.14; 95% CI 1.03-4.45), and of perceiving EEE as a threat compared to cancer (OR 2.18; 95% CI 1.24-3.84). Media treatment of health stories that emphasize the novelty and unpredictability of EEE compared to cancer may lead to distorted perceptions of threat among news consumers. PMID- 20352481 TI - Disease maps as context for community mapping: a methodological approach for linking confidential health information with local geographical knowledge for community health research. AB - Health is increasingly understood as a product of multiple levels of influence, from individual biological and behavioral influences to community and societal level contextual influences. In understanding these contextual influences, community health researchers have increasingly employed both geographic methodologies, including Geographic Information Systems (GIS), and community participatory approaches. However, despite growing interest in the role for community participation and local knowledge in community health investigations, and the use of geographical methods and datasets in characterizing community environments, there exist few examples of research projects that incorporate both geographical and participatory approaches in addressing health questions. This is likely due in part to concerns and restrictions regarding community access to confidential health data. In order to overcome this barrier, we present a method for linking confidential, geocoded health information with community-generated experiential geographical information in a GIS environment. We use sophisticated disease mapping methodologies to create continuously defined maps of colorectal cancer in Iowa, then incorporate these layers in an open source GIS application as the context for a participatory community mapping exercise with participants from a rural Iowa town. Our method allows participants to interact directly with health information at a fine geographical scale, facilitating hypothesis generation regarding contextual influences on health, while simultaneously protecting data confidentiality. Participants are able to use their local, geographical knowledge to generate hypotheses about factors influencing colorectal cancer risk in the community and opportunities for risk reduction. This work opens the door for future efforts to integrate empirical epidemiological data with community generated experiential information to inform community health research and practice. PMID- 20352482 TI - Norisoboldine inhibits the production of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells by down-regulating the activation of MAPKs but not NF-kappaB. AB - Norisoboldine is the main isoquinoline alkaloid occurring in Radix Linderae, the dry roots of Lindera aggregata (Lauraceae family). It has been previously implicated to be able to ameliorate the synovial inflammation and abnormal immune conditions in collagen-induced arthritis of mice. To get insight to the potential anti-inflammatory mechanisms of this alkaloid compound, the present study was undertaken to explore the effects of norisoboldine on the production of pro inflammatory cytokines from macrophages stimulated by lipopolysaccharide. In vitro, norisoboldine substantially reduced the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha as well as interleukin (IL)-1beta from RAW264.7 macrophage cells in a concentration-dependent manner, whereas it only slightly reduced the production of interleukin-6 (IL-6) at both protein and transcription levels. Of note, the preventive effects of norisoboldine on the release of pro inflammatory cytokines were correlated with the inhibitory action on the phosphorylations of mitogen-activated protein (MAP) kinases including p38, extracellular signal-regulated kinase (ERK) and c-jun NH(2)-terminal kinase (JNK), but not on the activation and translocation of nuclear factor-kappaB (NF kappaB). It can be therefore concluded that norisoboldine inhibits the macrophage activation and the resultant production of pro-inflammatory cytokines via down regulating the activation of MAPKs signaling pathways rather than NF-kappaB. PMID- 20352483 TI - Sequence analysis of VP2 gene of canine parvovirus isolates in Thailand. AB - Canine parvovirus (CPV) causes a very severe enteric disease especially in puppies. Twenty-six isolates of CPV were obtained from dogs at the Animal Hospital, Kasetsart University, Thailand. Whole VP2 gene of 26 isolates was amplified using polymerase chain reaction (PCR) and its sequences were analyzed. Nineteen out of 26 isolates were characterized as CPV type 2a variants and the rest of the isolates were characterized as CPV type 2b. These results indicated that both types are currently prevalent field CPV circulating in Thailand and type 2a is the predominant genotype. Neither CPV type 2 nor type 2c was observed in this study. PMID- 20352484 TI - Molecular characterization of two Chinese isolates of Beet western yellows virus infecting sugar beet. AB - Beet western yellows virus (BWYV) has previously been reported as an agent of sugar beet yellowing disease in China. In this article, the complete genomic RNA sequences of two Chinese BWYV isolates infecting beet from Inner Mongolia (BWYV IM) and Gansu (BWYV-GS) were determined and compared with three beet poleroviruses (BMYV, BChV and BWYV-US) and other non-beet-infecting poleroviruses. The genomes of the two isolates were 5,668 nt in length, and had almost the same genomic organization and characteristics as BWYV-US. The full length of BWYV-IM shared nucleotide sequence identities of 97.4, 86.6, 64.4 and 70.8% with BWYV-GS, BWYV-US, BChV and BMYV, respectively. Further sequence analysis indicated that the Chinese BWYV isolates were more closely related to BWYV-US; however, the identity of any gene product between the Chinese isolates and BWYV-US was <90%. Therefore, on the basis of genome sequence, we propose that these Chinese isolates are a distinct strain of BWYV that infect sugar beet. In addition, recombinant detection analysis revealed that BWYV-IM might be a recombinant virus. PMID- 20352485 TI - Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer. AB - OBJECTIVE: To investigate the relationship between antioxidant nutrients (vitamins C and E, beta-carotene, selenium) and DNA methylation-related nutrients (folate, vitamins B6 and B12) and distal colorectal cancer risk in whites and African Americans and to examine intakes from food only versus total (food plus dietary supplements) intakes. METHODS: Data are from the North Carolina Colon Cancer Study-Phase II, a case-control study of 945 distal colorectal cancer (including sigmoid, rectosigmoid, and rectum) cases and 959 controls. In-person interviews captured usual dietary intake and various covariates. Multivariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: High intakes of each antioxidant and DNA methylation related nutrient were significantly associated with lower risk in whites. In African Americans, the highest category of selenium from food only had a marginally significant inverse association with distal colorectal cancer risk (Q4 vs. Q1 OR: 0.55, 95% CI 0.29-1.02). Supplements did not provide additional risk reduction beyond intakes from food. CONCLUSIONS: Our findings provide evidence that antioxidant and DNA methylation-related nutrients may lower the risk of distal colorectal cancer in whites, and selenium may lower risk in African Americans. Optimal micronutrient intakes from food alone may be more beneficial than supplementation. PMID- 20352486 TI - Conflict of interest in economic analyses of aromatase inhibitors in breast cancer: a systematic review. AB - To determine whether authors conducting economic analyses of aromatase inhibitors in breast cancer are less likely to reach unfavorable conclusions if the economic study is sponsored by the manufacturer of the drug. Articles reporting the economic analyses of aromatase inhibitors in breast cancer were selected from PubMed in May 2009. Information was collected on the types of analysis, the qualitative conclusion, the quantitative results, and the funding sources. Fisher's exact test was conducted to compare the frequency of unfavorable conclusions based on study sponsorship. Thirty-two eligible articles were identified. Twenty-six were funded by pharmaceutical companies, and 4 were funded by non-pharmaceutical companies. Two studies did not report a funding source. Twenty-one studies evaluated aromatase inhibitors in the adjuvant setting, while 11 studies examined their use in advanced breast cancer. Twenty-two studies evaluated one type aromatase inhibitor, while 10 compared multiple types of aromatase inhibitors. Only one of the 26 (4%) pharmaceutical company-sponsored studies reported unfavorable cost-effectiveness of an aromatase inhibitor, which was a competitor's product, whereas two of four (50%) non-pharmaceutical company sponsored studies concluded aromatase inhibitors are not cost-effective in certain clinical scenarios (P < 0.05). Seven pharmaceutical company-sponsored studies conducted a comparison among several aromatase inhibitors; all 7 studies reported favorable conclusions for the sponsoring company's products. The majority of economic analyses of aromatase inhibitors in breast cancer are sponsored by pharmaceuticals. Economic evaluations of aromatase inhibitors in breast cancer that are funded by a pharmaceutical company are less likely to reach unfavorable conclusions about the sponsor's product. PMID- 20352487 TI - Mutations and polymorphic BRCA variants transmission in breast cancer familial members. AB - We previously showed that about 80% of breast cancer patients at high risk to carry mutation in BRCA genes presented at least one polymorphism in these genes which resulted potentially harmful by in silico analysis. In the present paper, the genealogic transmission of those polymorphic coding and noncoding variants of BRCA genes in family's members has been investigated. Thirty families, enrolled within the Genetic Counselling Program of our Institute, with probands and at least one-first degree relative (n = 67 family members) available, have been studied for both BRCA1 and BRCA2 pathological mutation and polymorphic variants' transmission. Ten and 6 probands carried Mendelian transmitted mutations in BRCA1 and BRCA2, respectively. Polymorphic coding and noncoding variants were transmitted in each family's relatives with a frequency ranging from 42 to 100%, with similar rate for each SNP in mutated and nonmutated families with the only exception of BRCA1 K1183R significantly more frequent in mutated families (P = 0.004); conversely, this SNP and BRCA2 N372H, were more frequently present in breast cancer relatives belonging to families in which pathological BRCA mutations were not present. Furthermore, specific haplotypes were transmitted in all relatives as BRCA1 871Leu-1038Gly, present in both BRCA mutated and nonmutated families, while BRCA2 289His-991Asp-IVS14+53 C>T present only in BRCAX families suggesting the harmful role of these SNPs. In conclusion, analysis of SNPs maps and modality of their transmission could identify further susceptibility markers and provide a basis for a better DNA-based cancer classification. PMID- 20352488 TI - Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer. AB - Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention as a prognostic factor in breast cancer. We aimed to validate the influence of Ep CAM RNA expression in untreated node-negative breast cancer. Ep-CAM RNA expression was evaluated utilizing microarray-based gene-expression profiling in 194 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. The prognostic significance of Ep-CAM RNA expression for disease-free survival (DFS), metastasis-free survival (MFS), and breast cancer-specific overall survival (OS) was evaluated in univariate and multivariate analysis adjusted for age, grading, pTstage, ER as well as PR receptor and HER-2 status. Additionally, Ep-CAM RNA expression was compared with immunohistochemistry (IHC) for Ep-CAM in 194 patients. The prognostic impact of Ep-CAM gene expression was validated in further 588 node-negative breast cancer patients. Levels of Ep-CAM RNA expression showed a significant correlation with IHC (P = 0.001) and predicted in univariate analysis DFS (P = 0.001, HR = 2.4), MFS (P = 0.003, HR = 2.5), and OS (P = 0.002, HR = 3.1) accurately. The prognostic influence of Ep-CAM RNA was significant also in multivariate analysis for DFS (P = 0.017, HR = 2.0), MFS (P = 0.049, HR = 1.9), and OS (P = 0.042, HR = 2.3), respectively. The association with MFS was confirmed in an independent validation cohort in univariate (P = 0.006, HR = 1.9) and multivariate (P = 0.035, HR = 1.7) analysis. Ep-CAM RNA correlated with the proliferation metagene (P < 0.001, R=0.425) Nevertheless, in multivariate analysis, Ep-CAM was associated with MFS independent from the proliferation metagene (P = 0.030, HR = 1.8). In conclusion, Ep-CAM RNA expression is associated with poor MFS in three cohorts of untreated node-negative breast cancer. PMID- 20352489 TI - Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. AB - Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, an understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidences for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L: -serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L: -serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L: -serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L: -serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. PMID- 20352490 TI - Protection against direct in-contact challenge following foot-and-mouth disease vaccination in sheep and goats: the effect on virus excretion and carrier status. AB - The ability of foot-and-mouth disease (FMD) vaccine to protect sheep and goats from a homologous direct in-contact challenge and the effect on virus excretion from the nasal secretions and oropharynx was examined. An experimental oil adjuvant O(1) Manisa FMD vaccine protected sheep and goats from clinical disease from 7 days post vaccination following 24 hours of direct in-contact exposure to four infected donor sheep or goats. Goats required lower antibody titres for protection when compared with sheep. Protection from clinical disease did not prevent localized viral replication in goats and at least two goats had viral RNA detected on day 28 post challenge. Quantitative reverse transcriptase polymerase chain reaction showed that the level of virus replication shortly after direct in contact challenge in oropharynx and nasal secretions of vaccinated animals was reduced by 100 and 1000 times respectively when compared with unvaccinated controls. The findings also show that after direct in-contact challenge, use of FMD vaccine will prevent or reduce local virus replication, thereby significantly reduce the amount of virus released into the environment in the all-important early post-exposure period. There is low risk of vaccinated animals transmitting disease as live virus could not be readily isolated. PMID- 20352491 TI - The metacognitive model of generalized anxiety disorder in children and adolescents. AB - Worry is a common phenomenon in children and adolescents, with some experiencing excessive worries that cause significant distress and interference. The metacognitive model of generalized anxiety disorder (Wells 1995, 2009) was developed to explain cognitive processes associated with pathological worry in adults, particularly the role of positive and negative beliefs about worry. This review evaluates the application of the model in understanding child and adolescent worry. Other key issues reviewed include the link between cognitive and metacognitive development and worry, and the measurement of worry and metacognitive worry in young people. Implications of these findings and directions for future research are discussed. PMID- 20352492 TI - Alcohol, marijuana, and tobacco use among Canadian youth: do we need more multi substance prevention programming? AB - Data from the Canadian Youth Smoking Survey (n = 27,030 in 2006; n = 16,705 in 2004; n = 11,757 in 2002) were used to examine changes in the prevalence and comorbid use of alcohol, tobacco, and marijuana over time and examine if demographic factors and binge drinking are associated with comorbid substance use among youth. Alcohol was the most prevalent substance used, and it was rare to find youth who had used tobacco or marijuana without also having tried alcohol. Youth who reported binge drinking were substantially more likely to also have tried tobacco and/or marijuana. These data suggest that multi-substance prevention programs are required for youth populations. PMID- 20352493 TI - Variability of United States isolates of Macrophomina phaseolina based on simple sequence repeats and cross genus transferability to related genera within botryosphaeriaceae. AB - Twelve simple sequence repeat (SSRs) loci were used to evaluate genetic diversity of 109 isolates of Macrophomina phaseolina collected from different geographical regions and host species throughout the United States (US). Genetic diversity was assessed using Nei's minimum genetic distance, and the usefulness of each locus was determined by calculating the polymorphism information content (PIC). A total of 98 alleles were detected and of these 31 were unique to individual genotypes. Eight of twelve loci were highly informative with PIC values greater than 0.50. The majority of pairwise comparisons of genetic distance were greater than 0.60 indicating moderate to high genetic diversity. Dendrograms based on the genetic dissimilarities were created for the 109 isolates of which 79 were from soybean. Some clustering by host and geography was noted, but, the dendrograms generally grouped isolates independent of host or geography. Additionally, sequencing of the internal transcribed spacer region (ITS) for 10 isolates revealed that all of these isolates were 99% similar. Three SSR loci from M. phaseolina were cross amplified in other genera in the Botryosphaeriaceae. This was the first study of genotyping and assessing genetic diversity of M. phaseolina isolates collected from a widespread host and geographic range across the US with SSRs. With an additional 34 loci publically available for M. phaseolina, the results indicate that previously developed SSRs from one species can be used in future population, ecological, and genetic studies of M. phaseolina and other genera within the Botryosphaeriaceae. PMID- 20352494 TI - The cell wall fraction from Fonsecaea pedrosoi stimulates production of different profiles of cytokines and nitric oxide by murine peritoneal cells in vitro. AB - Chromoblastomycosis is a chronic, suppurative and granulomatous mycosis whose main etiologic agent is the fungus Fonsecaea pedrosoi. The severity of chromoblastomycosis clinical manifestations correlates with the Th1 or Th2 immune response, and an efficient cellular immune response depends on the interaction between immune cells and the cell wall of the fungi, which is able to promote this activation. The objective of this study was to analyze the influence of cell wall fractions of Fonsecaea pedrosoi on the activation of peritoneal phagocytes obtained from mice. Our results revealed that after 4 h of inoculation with fungal cell wall components, there was a cell migration predominantly comprised of neutrophils followed, after 72 h, by migration of the macrophages. After 4 h, the F2 fraction caused increased production of nitric oxide in phagocytes, but this effect was not observed in the phagocytes after 72 h. The F1 fraction stimulated production of IL-12 in cells that migrated after 72 h, while the inactivated fungus and the F2 fraction led to production of IL-10. The F2 fraction decreased the rate of phagocytosis and increased the production of IL 10. Our results suggest that the F2 fraction and its components caused an important disruption of microbicidal mechanisms negatively modulating the immune response and favoring the persistence of the fungus. PMID- 20352496 TI - Saponified evening primrose oil reduces melanogenesis in B16 melanoma cells and reduces UV-induced skin pigmentation in humans. AB - This study was conducted to determine whether saponified evening primrose oil (sap-EPO) has the potential for use as a whitening agent and to investigate its underlying mechanisms of action. In B16 melanoma cells, sap-EPO dose-dependently inhibited isobutylmethylxanthine-induced melanogenesis with no cytotoxicity. This decrease in melanin production was correlated with reduced enzyme activity and decreased mRNA and protein levels of tyrosinase. The mRNA levels of tyrosinase related proteins 1 and 2 decreased in response to treatment with sap-EPO, indicating that it regulated tyrosinase at the transcriptional level. Expression of microphthalmia-associated transcription factor was also decreased by sap-EPO as evidenced by decreased mRNA and protein levels. Additionally, topical application of sap-EPO resulted in efficient whitening of UVB-induced hyperpigmentation of human skin. Taken together, these results suggest that sap EPO has the potential for use as a cosmetic whitening agent. PMID- 20352495 TI - Maximal sensitive dependence and the optimal path to epidemic extinction. AB - Extinction of an epidemic or a species is a rare event that occurs due to a large, rare stochastic fluctuation. Although the extinction process is dynamically unstable, it follows an optimal path that maximizes the probability of extinction. We show that the optimal path is also directly related to the finite-time Lyapunov exponents of the underlying dynamical system in that the optimal path displays maximum sensitivity to initial conditions. We consider several stochastic epidemic models, and examine the extinction process in a dynamical systems framework. Using the dynamics of the finite-time Lyapunov exponents as a constructive tool, we demonstrate that the dynamical systems viewpoint of extinction evolves naturally toward the optimal path. PMID- 20352497 TI - Disparities in health and health care across a range of populations and conditions. Introduction. PMID- 20352498 TI - Improving underrepresented minority medical student recruitment with health disparities curriculum. AB - BACKGROUND: Diversity improves all students' academic experiences and their abilities to work with patients from differing backgrounds. Little is known about what makes minority students select one medical school over another. PURPOSE: To measure the impact of the existence of a health disparities course in the medical school curriculum on recruitment of underrepresented minority (URM) college students to the University of Chicago Pritzker School of Medicine. METHODS: All medical school applicants interviewed in academic years 2007 and 2008 at the University of Chicago Pritzker School of Medicine (PSOM) attended an orientation that detailed a required health care disparities curriculum introduced in 2006. Matriculants completed a precourse survey measuring the impact of the existence of the course on their decision to attend PSOM. URM was defined by the American Association of Medical Colleges as Black, American Indian/Alaskan Native, Native Hawaiian, Mexican American, and Mainland Puerto Rican. RESULTS: Precourse survey responses were 100% and 96% for entering classes of 2007 and 2008, respectively. Among those students reporting knowledge of the course (128/210, 61%), URM students (27/37, 73%) were more likely than non-URM students (38/91, 42%) to report that knowledge of the existence of the course influenced their decision to attend PSOM (p = 0.002). Analysis of qualitative responses revealed that students felt that the curriculum gave the school a reputation for placing importance on health disparities and social justice issues. URM student enrollment at PSOM, which had remained stable from years 2005 and 2006 at 12% and 11% of the total incoming classes, respectively, increased to 22% of the total class size in 2007 (p = 0.03) and 19 percent in 2008. CONCLUSION: The required health disparities course may have contributed to the increased enrollment of URM students at PSOM in 2007 and 2008. PMID- 20352499 TI - Assessing patient-centered care: one approach to health disparities education. AB - BACKGROUND: Patient-centered care has been described as one approach to cultural competency education that could reduce racial and ethnic health disparities by preparing providers to deliver care that is respectful and responsive to the preferences of each patient. In order to evaluate the effectiveness of a curriculum in teaching patient-centered care (PCC) behaviors to medical students, we drew on the work of Kleinman, Eisenberg, and Good to develop a scale that could be embedded across cases in an objective structured clinical examination (OSCE). OBJECTIVE: To compare the reliability, validity, and feasibility of an embedded patient-centered care scale with the use of a single culturally challenging case in measuring students' use of PCC behaviors as part of a comprehensive OSCE. METHODS: A total of 322 students from two California medical schools participated in the OSCE as beginning seniors. Cronbach's alpha was used to assess the internal consistency of each approach. Construct validity was addressed by establishing convergent and divergent validity using the cultural challenge case total score and OSCE component scores. Feasibility assessment considered cost and training needs for the standardized patients (SPs). RESULTS: Medical students demonstrated a moderate level of patient-centered skill (mean = 63%, SD = 11%). The PCC Scale demonstrated an acceptable level of internal consistency (alpha = 0.68) over the single case scale (alpha = 0.60). Both convergent and divergent validities were established through low to moderate correlation coefficients. DISCUSSION: The insertion of PCC items across multiple cases in a comprehensive OSCE can provide a reliable estimate of students' use of PCC behaviors without incurring extra costs associated with implementing a special cross-cultural OSCE. This approach is particularly feasible when an OSCE is already part of the standard assessment of clinical skills. Reliability may be increased with an additional investment in SP training. PMID- 20352500 TI - Medical students' perceptions of their teachers' and their own cultural competency: implications for education. AB - BACKGROUND: Enhancing the cultural competency of students is emerging as a key issue in medical education; however, students may perceive that they are more able to function within cross-cultural situations than their teachers, reducing the effectiveness of cultural competency educational efforts. OBJECTIVE: The purpose of our study was to compare medical students' perceptions of their residents, attendings, and their own cultural competency. DESIGN: Cross-sectional study. MAIN MEASURES: A questionnaire containing previously validated instruments was administered to end-of-third-year medical students at four institutions throughout the US. Repeated measures multivariate analysis was used to determine differences in student ratings. PARTICIPANTS: Three hundred fifty-eight medical students from four schools participated, for an overall response rate of 65%. RESULTS: Analysis indicated overall statistically significant differences in students' ratings (p < 0.001, eta(2) = 0.33). Students rated their own cultural competency as statistically significantly higher than their residents, but similar to their attendings. For reference, students rated the patient care competency of themselves, their residents, and their attendings; they rated their attendings' skills as statistically significantly higher than residents, and residents as statistically significantly higher than themselves. There were differences between cultural competency and patient care ratings. CONCLUSIONS: Our results indicate that students perceive the cultural competency of their attendings and residents to be the same or lower than themselves. These findings indicate that this is an important area for future research and curricular reform, considering the vital role that attendings and residents play in the education of medical students. PMID- 20352501 TI - Teaching about health care disparities in the clinical setting. AB - Clinical teachers often observe interactions that may contribute to health care disparities, yet may hesitate to teach about them. A pedagogical model could help faculty structure teaching about health care disparities in the clinical setting, but to our knowledge, none have been adapted for this purpose. In this paper, we adapt an established model, Time-Effective Strategies for Teaching (TEST), to the teaching of health care disparities. We use several case scenarios to illustrate the core components of the model: diagnose the learner, teach rapidly to the learner's need, and provide feedback. The TEST model is straightforward, easy to use, and enables the incorporation of teaching about health care disparities into routine clinical teaching. PMID- 20352502 TI - Disparities education: what do students want? AB - BACKGROUND: Educating medical students about health disparities may be one step in diminishing the disparities in health among different populations. According to adult learning theory, learners' opinions are vital to the development of future curricula. DESIGN: Qualitative research using focus group methodology. OBJECTIVES: Our objectives were to explore the content that learners value in a health disparities curriculum and how they would want such a curriculum to be taught. PARTICIPANTS: Study participants were first year medical students with an interest in health disparities (n = 17). APPROACH: Semi-structured interviews consisting of 12 predetermined questions, with follow-up and clarifying questions arising from the discussion. Using grounded theory, codes were initially developed by the team of investigators, applied, and validated through an iterative process. MAIN RESULTS: The students perceived negative attitudes towards health disparities education as a potential barrier towards the development of a health disparities curriculum and proposed possible solutions. These solutions centered around the learning environment and skill building to combat health disparities. CONCLUSIONS: While many of the students' opinions were corroborated in the literature, the most striking differences were their opinions on how to develop good attitudes among the student body. Given the impact of the provider on health disparities, how to develop such attitudes is an important area for further research. PMID- 20352503 TI - Surmounting the unique challenges in health disparities education: a multi institution qualitative study. AB - BACKGROUND: The National Consortium for Multicultural Education for Health Professionals (Consortium) comprises educators representing 18 US medical schools, funded by the National Institutes of Health. Collective lessons learned from curriculum implementation by principal investigators (PIs) have the potential to guide similar educational endeavors. OBJECTIVE: Describe Consortium PI's self-reported challenges with curricular development, solutions and their new curricular products. METHODS: Information was collected from PIs over 2 months using a 53-question structured three-part questionnaire. The questionnaire addressed PI demographics, curriculum implementation challenges and solutions, and newly created curricular products. Study participants were 18 Consortium PIs. Descriptive analysis was used for quantitative data. Narrative responses were analyzed and interpreted using qualitative thematic coding. RESULTS: Response rate was 100%. Common barriers and challenges identified by PIs were: finding administrative and leadership support, sustaining the momentum, continued funding, finding curricular space, accessing and engaging communities, and lack of education research methodology skills. Solutions identified included engaging stakeholders, project-sharing across schools, advocacy and active participation in committees and community, and seeking sustainable funding. All Consortium PIs reported new curricular products and extensive dissemination efforts outside their own institutions. CONCLUSION: The Consortium model has added benefits for curricular innovation and dissemination for cultural competence education to address health disparities. Lessons learned may be applicable to other educational innovation efforts. PMID- 20352504 TI - When best intentions aren't enough: helping medical students develop strategies for managing bias about patients. AB - INTRODUCTION/AIMS: Implicit bias can impact physician-patient interactions, alter treatment recommendations, and perpetuate health disparities. Medical educators need methods for raising student awareness about the impact of bias on medical care. SETTING: Seventy-two third-year medical student volunteers participated in facilitated small group discussions about bias. PROGRAM DESCRIPTION: We tested an educational intervention to promote group-based reflection among medical students about implicit bias. PROGRAM EVALUATION: We assessed how the reflective discussion influenced students' identification of strategies for identifying and managing their potential biases regarding patients. 67% of the students (n = 48) identified alternate strategies at post-session. A chi-square analysis demonstrated that the distribution of these strategies changed significantly from pre-session to post-session (chi(2)(11) = 27.93, p < 0.01), including reductions in the use of internal feedback and humanism and corresponding increases in the use of reflection, debriefing and other strategies. DISCUSSION: Group-based reflection sessions, with a provocative trigger to foster engagement, may be effective educational tools for fostering shifts in student reflection about bias in encounters and willingness to discuss potential biases with colleagues, with implications for reducing health disparities. PMID- 20352505 TI - Reflective practice enriches clerkship students' cross-cultural experiences. AB - AIM: To describe a curriculum incorporating written reflection followed by reflective discussion with the goal of enhancing students' recognition and handling of cross-cultural and health disparity issues in different healthcare delivery settings. PROGRAM AND SETTING: This required curriculum was implemented within a 4-week family medicine clerkship (n = 188 students, 6 to 12 per rotation) in 23 successive rotations over 2 years. Electronic submission of a written assignment in response to structured questions was followed by in-class discussion in week 4. PROGRAM EVALUATION: Outcomes were students' session evaluations, thematic analysis of student responses, and analysis of faculty facilitators' reflections about discussion sessions. Students' cultural knowledge about their patients' health beliefs around diabetes was assessed using multiple choice questions at the beginning and end of the clerkship. RESULTS: One hundred percent of students submitted narratives. Student evaluations demonstrated high acceptance, appreciation of sessions and faculty. Analyses of written assignments and in-class discussions identified recurring themes. Students achieved greater synthesis and more nuanced understanding of cross-cultural encounters after discussion. Self-rating of confidence in addressing cultural issues after the curriculum was high at 3.17 +/- SD 0.57 (1-4). Cultural knowledge scores improved significantly. Core components for success were clerkship director support, required participation, experienced faculty facilitators without evaluative roles, a structured assignment and formal forum for trigger question discussion. DISCUSSION: Written reflection followed by facilitated peer discussion adds value to simple 'exposure' to cross-cultural clinical experiences for medical students. PMID- 20352507 TI - Community-based teaching about health disparities: combining education, scholarship, and community service. AB - The Institute of Medicine recommends that clinicians receive training to better understand and address disparities. While disparities in health status are primarily due to inequities in social determinants of health, current curricula largely focus on how to teach about disparities within the health care setting. Learners may more fully understand and appreciate how social contextual factors contribute to disparities through instruction about disparities in community settings. Community-based teaching about health disparities may be advantageous for learners, medical institutions, and participating communities. This manuscript aims to guide medical educators in teaching students and residents about health disparities through community-based activities, including service learning and research. PMID- 20352506 TI - Cancer risk communication with low health literacy patients: a continuing medical education program. AB - BACKGROUND: Low health literacy (HL) is an important risk factor for cancer health disparities. OBJECTIVE: Describe a continuing medical education (CME) program to teach primary care physicians (PCP) cancer risk communication and shared decision-making (SDM) with low HL patients and baseline skills assessment. DESIGN: Cluster randomized controlled trial in five primary care clinics in New Orleans, LA. PARTICIPANTS: Eighteen PCPs and 73 low HL patients overdue for cancer screening. INTERVENTION: Primary care physicians completed unannounced standardized patient (SP) encounters at baseline. Intervention physicians received SP verbal feedback; academic detailing to review cancer screening guidelines, red flags for identifying low HL, and strategies for effective counseling; and web-based tutorial of SP comments and checklist items hyperlinked to reference articles/websites. MAIN MEASURES: Baseline PCP self-rated proficiency, SP ratings of physician general cancer risk communication and SDM skills, patient perceived involvement in care. RESULTS: Baseline assessments show physicians rated their proficiency in discussing cancer risks and eliciting patient preference for treatment/decision-making as "very good". SPs rated physician exploration of perceived cancer susceptibility, screening barriers/motivators, checking understanding, explaining screening options and associated risks/benefits, and eliciting preferences for screening as "satisfactory". Clinic patients rated their doctor's facilitation of involvement in care and information exchange as "good". However, they rated their participation in decision-making as "poor". DISCUSSION: The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program. PMID- 20352508 TI - Medical-legal partnership: collaborating with lawyers to identify and address health disparities. AB - INTRODUCTION: Medical-legal partnerships (MLPs) bring together medical professionals and lawyers to address social causes of health disparities, including access to adequate food, housing and income. SETTING: Eighty-one MLPs offer legal services for patients whose basic needs are not being met. PROGRAM DESCRIPTION: Besides providing legal help to patients and working on policy advocacy, MLPs educate residents (29 residency programs), health care providers (160 clinics and hospitals) and medical students (25 medical schools) about how social conditions affect health and screening for unmet basic needs, and how these needs can often be impacted by enforcing federal and state laws. These curricula include medical school courses, noon conferences, advocacy electives and CME courses. PROGRAM EVALUATION: Four example programs are described in this paper. Established MLPs have changed knowledge (MLP | Boston-97% reported screening for two unmet needs), attitudes (Stanford reported reduced concern about making patients "nervous" with legal questions from 38% to 21%) and behavior (NY LegalHealth reported increasing resident referrals from 15% to 54%) after trainings. One developing MLP found doctors experienced difficulty addressing social issues (NJ LAMP-67% of residents felt uncomfortable). DISCUSSION: MLPs train residents, students and other health care providers to tackle socially caused health disparities. PMID- 20352509 TI - A model for interprofessional health disparities education: student-led curriculum on chronic hepatitis B infection. AB - BACKGROUND: Although health disparities are commonly addressed in preclinical didactic curricula, direct patient care activities with affected communities are more limited. PURPOSE: To address this problem, health professional students designed a preclinical service-learning curriculum on hepatitis B viral (HBV) infection, a major health disparity affecting the Asian/Pacific Islander (API) population, integrating lectures, skills training, and direct patient care at student-run clinics. SETTING: An urban health professions campus. METHODS: Medical and other health professional students at University of California, San Francisco, organized a preclinical didactic and experiential elective, and established two monthly clinics offering HBV screening, vaccination, and education to the community. RESULTS: Between 2004 and 2009, 477 students enrolled in the student-led HBV curriculum. Since the clinics' inception in 2007, 804 patients have been screened for chronic HBV; 87% were API immigrants, 63% had limited English proficiency, and 46% were uninsured. Serologically, 10% were found to be chronic HBV carriers, 44% were susceptible to HBV, and 46% were immune. DISCUSSION: Our student-led didactic and experiential elective can serve as an interprofessional curricular model for learning about specific health disparities while providing important services to the local community. PMID- 20352510 TI - Treating and precepting with RESPECT: a relational model addressing race, ethnicity, and culture in medical training. AB - BACKGROUND: In 2000 a diverse group of clinicians/educators at an inner-city safety-net hospital identified relational skills to reduce disparities at the point of care. DESCRIPTION: The resulting interviewing and precepting model helps build trust with patients as well as with learners. RESPECT adds attention to the relational dimension, addressing documented disparities in respect, empathy, power-sharing, and trust while incorporating prior cross-cultural models. Specific behavioral descriptions for each component make RESPECT a concrete, practical, integrated model for teaching patient care. CONCLUSIONS: Precepting with RESPECT fosters a safe climate for residents to partner with faculty, address challenges with patients at risk, and improve outcomes. PMID- 20352511 TI - Beyond knowledge, toward linguistic competency: an experiential curriculum. AB - INTRODUCTION/AIMS: Training is essential for future health care providers to effectively communicate with limited English proficient (LEP) patients during interpreted encounters. Our aim is to describe an innovative skill-based medical school linguistic competency curriculum and its impact on knowledge and skills. SETTING: At Stanford University School of Medicine, we incorporated a linguistic competency curriculum into a 2-year Practice of Medicine preclinical doctoring course and pediatrics clerkship over three cohorts. PROGRAM DESCRIPTION: First year students participated in extensive interpreter-related training including: a knowledge-based online module, interactive role-play exercises, and didactic skill-building sessions. Students in the pediatrics clerkship participated in interpreted training exercises with facilitated feedback. PROGRAM EVALUATION: Knowledge and skills were evaluated in the first and fourth years. First year students' knowledge scores increased (pre-test = 0.62, post-test = 0.89, P < 0.001), and they demonstrated good skill attainment during an end-year performance assessment. One cohort of students participated in the entire curriculum and maintained performance into the fourth year. DISCUSSION: Our curriculum increased knowledge and led to skill attainment, each of which showed good durability for a cohort of students evaluated 3 years later. With a growing LEP population, these skills are essential to foster in future health care providers to effectively communicate with LEP patients and reduce health disparities. PMID- 20352512 TI - A strategy for improving health disparities education in medicine. AB - INTRODUCTION: A health disparities curriculum that uses evidence-based knowledge rooted in pedagogic theory is needed to educate health care providers to meet the needs of an increasingly diverse U.S. population. DESCRIPTION: The Health Disparities Education: Beyond Cultural Competency Precourse, along with its accompanying Train the Trainer Guide: Health Disparities Education (2008), developed by the Society of General Internal Medicine (SGIM) Disparities Task Force (DTF), is a comprehensive tool to facilitate developing, implementing and evaluating health disparities education. The curriculum includes five modules highlighting several fundamental concepts in health disparities, suggestions for teaching about health disparities in a wide range of settings and strategies for curriculum evaluation. The modules are Disparities Foundations, Teaching Disparities in the Clinical Setting, Disparities Beyond the Clinical Setting, Teaching about Disparities Through Community Involvement, and Curriculum Evaluation. EVALUATION: All five modules were delivered as a precourse at the 31st Annual SGIM Annual Meeting in Pittsburgh, PA and received the "Best Precourse Award". This award is given to the most highly rated precourse based on participant evaluations. The modules have also been adapted into a web-based guide that has been downloaded at least 59 times. CONCLUSION: Ultimately, the modules are designed to develop a professional commitment to eliminating racial and ethnic disparities in health care quality, promote an understanding of the role of health care providers in reducing health care disparities through comprehensive education and training, and provide a framework with which providers can address the causes of disparities in various educational settings. PMID- 20352513 TI - Teaching cultural diversity: current status in U.K., U.S., and Canadian medical schools. AB - In this paper we present the current state of cultural diversity education for undergraduate medical students in three English-speaking countries: the United Kingdom (U.K.), United States (U.S.) and Canada. We review key documents that have shaped cultural diversity education in each country and compare and contrast current issues. It is beyond the scope of this paper to discuss the varied terminology that is immediately evident. Suffice it to say that there are many terms (e.g. cultural awareness, competence, sensitivity, sensibility, diversity and critical cultural diversity) used in different contexts with different meanings. The major issues that all three countries face include a lack of conceptual clarity, and fragmented and variable programs to teach cultural diversity. Faculty and staff support and development, and ambivalence from both staff and students continue to be a challenge. We suggest that greater international collaboration may help provide some solutions. PMID- 20352515 TI - The role of worldviews in health disparities education. AB - Worldviews are sets of beliefs and assumptions that express how cultures interpret and explain their experience. Worldview has been a useful explanatory construct in the social science literature, but has been used less often in the context of human health. Reducing and ultimately eliminating the negative role that health care providers play in producing health disparities will require a cultural change. Here I posit that "worldview" is a critically important concept for health disparities education that overtime will serve to transform the culture of health care professionals toward a more self-reflective, humble, and open-minded posture. PMID- 20352514 TI - Stereotype threat and health disparities: what medical educators and future physicians need to know. AB - Patients' experience of stereotype threat in clinical settings and encounters may be one contributor to health care disparities. Stereotype threat occurs when cues in the environment make negative stereotypes associated with an individual's group status salient, triggering physiological and psychological processes that have detrimental consequences for behavior. By recognizing and understanding the factors that can trigger stereotype threat and understanding its consequences in medical settings, providers can prevent it from occurring or ameliorate its consequences for patient behavior and outcomes. In this paper, we discuss the implications of stereotype threat for medical education and trainee performance and offer practical suggestions for how future providers might reduce stereotype threat in their exam rooms and clinics. PMID- 20352516 TI - Teaching about health disparities using a social determinants framework. AB - The intersection of two trends in health intervention has the potential to fundamentally change the practice of medicine. First, research into the social determinants of health is revealing the mechanisms by which living conditions cause disease. Second, the restructuring of primary care around preventive interventions represents the convergence point of medicine and public health. These trends have profound implications for medical education. Whereas traditional educational paradigms favor a "bottom-up" approach to disease focusing on molecular origins or organ systems-new paradigms must emphasize the entire causal chain of ill health to facilitate the understanding of novel interventions available to tomorrow's clinician. PMID- 20352517 TI - Fulfilling the mission of academic medicine: training residents in the health needs of prisoners. AB - The single mission of academic medicine is the pursuit of health for all. This mandate serves as a reminder to focus care on vulnerable and underserved populations. The 12 million Americans who cycle through correctional facilities each year are arguably among the most vulnerable populations in this country; predominantly black, with a high burden of disease and many barriers to care after release. Medical training programs should provide exposure to the health needs of prisoners. Residents could establish care with inmates prior to release and arrange follow-up in the community. This addition to training would not only provide care to this underserved group, but also would train residents in the myriad problems prisoners face, and foster social responsibility. PMID- 20352518 TI - Let's not contribute to disparities: the best methods for teaching clinicians how to overcome language barriers to health care. AB - Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching "Medical Spanish" or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one's own limited non-English language skills. PMID- 20352519 TI - Respect and empathy in teaching and learning cultural medicine. PMID- 20352520 TI - Teaching undergraduates about racial and ethnic disparities. PMID- 20352521 TI - What matters in health disparities education--changing hearts or minds? PMID- 20352522 TI - Medical legal partnerships: a key strategy for addressing social determinants of health. PMID- 20352523 TI - Viewing the future through the lens of the past: a personal reflection on disparities education in medicine and public health. PMID- 20352524 TI - Single vs repeated treatment with the intragastric balloon: a 5-year weight loss study. AB - BACKGROUND: Saline-filled intragastric balloons (IB) may be inserted for 6 months to promote weight loss. We aimed to assess potential benefits of repeating IB therapy. METHODS: One hundred eighteen consecutive subjects (median body mass index, 34.0 kg/m(2); interquartile range [IQR], 31.2-36.9) treated with IB were included in a prospective non-randomized multicenter study. RESULTS: Nineteen (16%) subjects had repeat IB therapy at their own request, either to prolong first treatment (n = 8) or after a IB-free interval (n = 11). Higher weight loss 3 months after first IB insertion independently predicted repeat therapy (P = 0.008). Median weight loss in subjects who had repeat therapy was lower with second vs first IB (9.0 vs 14.6 kg; 30.4% vs 49.3% excess weight [EW]; P = 0.003). Compared to subjects with single treatment (n = 99), those with repeat treatment (n = 19) had greater weight loss at first IB extraction (14.6 vs 11.0 kg; 49.3% vs 30.7% EW; P = 0.026) and 1 year later (12.0 vs 6.0 kg; 40.9% vs 20.8% EW; P = 0.008) but the difference became less than 2 kg starting at 3 years. At final follow-up (4.9 years; IQR, 3.4-6.7), the whole subject population had lost a median of 2.0 kg (IQR, -3.0 to 10.3) or 6.2% EW (IQR, -8.1 to 31.6) and identical proportions of subjects with single/repeat treatment had >or=10% baseline weight loss (26%) or bariatric surgery (32%). CONCLUSION: Higher weight loss at 3 months independently predicted repeat IB therapy; weight loss with the second IB was lower compared to first IB. Repeat treatment had no effect on proportions of subjects with >or=10% baseline weight loss or bariatric surgery at final follow-up. PMID- 20352525 TI - Obesity treatment using a Bioenterics intragastric balloon (BIB)--preliminary Croatian results. AB - AIM OF STUDY: This study aims to assess the effectiveness, tolerance, safety, and patient satisfaction of obesity treatments using the Bioenterics intragastric balloon (BIB). METHODS: Prospective controlled trial of 33 obese patients who were treated with the BIB from March 2008 to March 2009 and who completed the 6 months treatment. Patients were selected on the basis of workup by a multidisciplinary team. The 33 obese patients (26 females, seven males) had a median age of 35 years (range 20-58). Their median baseline body weight (BW) was 114 kg (range 89-197) and their median body mass index (BMI) was 41.4 kg/m(2) (range 31.2-60.8). RESULTS: Average weight reduction was 14 kg (range 2-37), loss total weight 10.1% (range 1.4-23.1), control BMI 35.6 kg/m(2) (range 29.4-50.3), delta BMI 4.5 (range 0.6-13.1), percentage excess weight loss 29.2 (range 2.8 53.6), and percent of excess BMI loss 29.3 (range 2.7-67.4). In one female patient the BIB was removed early due to intolerance. During the first week, minor side effects were noticed: nausea/vomiting occurred in 21 patients (63.6%), and abdominal cramps in 15 (45.5%). There was one balloon deflation and one impaction in the stomach. Those incidents were both successfully treated endoscopically. Patients had no major complications from mucosal lesions and no need for surgical interventions. All intragastric balloons were successfully removed endoscopically. Patients' treatment satisfaction correlated with the degree of BW loss (p = 0.0138). CONCLUSION: BIB treatment in our setting showed the best results for individuals with BMI from 35 to 40 kg/m(2). Our preliminary results showed that BIB is safe, well tolerated with minor side effects, and alters quality of life for the better. The complication rate was negligible, due to the detailed pretreatment examinations and follow-up. PMID- 20352526 TI - Estrogen receptors in immunity and autoimmunity. AB - Due to the female predominance of autoimmune diseases, the role of gender and sex hormones in the immune system is of long-term interest. Estrogen's primary effects are mediated via estrogen receptors alpha and beta (ER alpha/beta) that are expressed on most immune cells. ERs are nuclear hormone receptors that can either directly bind to estrogen response elements in gene promoters or serve as cofactors with other transcription factors (i.e., NFkB/AP1). Cytoplasmic ER and membrane associated ER impact specific kinase signaling pathways. ERs have prominent effects on immune function in both the innate and adaptive immune responses. Genetic deficiency of ERalpha in murine models of lupus resulted in significantly decreased disease and prolonged survival, while ERbeta deficiency had minimal to no effect in autoimmune models. The protective effect of ERalpha in lupus is multifactoral. In arthritis models, ERalpha agonists appears to mediate a protective effect. The modulation of ERalpha function appears to be a potential target for therapy in autoimmunity. PMID- 20352527 TI - Chemokines and their receptors in the allergic airway inflammatory process. AB - The development of the allergic airway disease conveys several cell types, such as T-cells, eosinophils, mast cells, and dendritic cells, which act in a special and temporal synchronization. Cellular mobilization and its complex interactions are coordinated by a broad range of bioactive mediators known as chemokines. These molecules are an increasing family of small proteins with common structural motifs and play an important role in the recruitment and cell activation of both leukocytes and resident cells at the allergic inflammatory site via their receptors. Trafficking and recruitment of cell populations with specific chemokines receptors assure the presence of reactive allergen-specific T-cells in the lung, and therefore the establishment of an allergic inflammatory process. Different approaches directed against chemokines receptors have been developed during the last decades with promising therapeutic results in the treatment of asthma. In this review we explore the role of the chemokines and chemokine receptors in allergy and asthma and discuss their potential as targets for therapy. PMID- 20352528 TI - The iPS technique provides hope for Parkinson's disease treatment. AB - More recently, reprogramming of somatic cells to an embryonic stem cell-like state presents a milestone in the realm of stem cells, making it possible to derive all cell types from any patients bearing specific genetic mutations. With the development of induced pluripotent stem (iPS) cells, we are now able to use the derivatives of iPS cells to study the mechanisms of disease and to perform drug screening and toxicology testing. In addition, differentiated iPS cells are now close to be used in clinical practice. Here we review the progress of iPS technique and the possible application in the area of Parkinson's disease treatment. PMID- 20352530 TI - Endoplasmic reticulum stress signals in defined human embryonic stem cell lines and culture conditions. AB - Human embryonic stem cells (hESCs) are especially resistant to several cellular stresses, but the existence and induction of Endoplasmic Reticulum (ER) stress by culture conditions are unknown. Using qPCR, here, we investigated the behavior of the principal sensors of ER stress and their relation with the feeder layer, the type of conditioned media used in feeder free systems and the upregulation of several differentiation markers. We observed the preservation of pluripotency, and detected differential expression of differentiation markers in HS181 and SHEF1 hESCs growing on Adipose-derived mesenchymal stem cells (ASCs) and feeder free system with different conditioned media (HEF-CM and ASC-CM). Taken together, these results demonstrate evidence of ER stress events that cells must resolve to survive and maintenance of markers of pluripotency. The early differentiation status defined could progress into a more differentiated state, and may be influenced by culture conditions. PMID- 20352531 TI - Solid state characterization of commercial crystalline and amorphous atorvastatin calcium samples. AB - Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot stage microscopy, scanning electron microscopy), contact angle, and intrinsic dissolution rate (IDR). All crystalline ATC samples were found to be stable form I, however one sample possessed polymorphic impurity, evidenced in XRPD and DSC analysis. Amongst the amorphous ATC samples, XRPD demonstrated five samples to be amorphous 'form 27', while, one matched amorphous 'form 23'. Thermal behavior of amorphous ATC samples was compared to amorphous ATC generated by melt quenching in DSC. ATC was found to be an excellent glass former with T(g)/T(m) of 0.95. Residual crystallinity was detected in two of the amorphous samples by complementary use of conventional and modulated DSC techniques. The wettability and IDR of all amorphous samples was found to be higher than the crystalline samples. In conclusion, commercial ATC samples exhibited diverse solid state behavior that can impact the performance and stability of the dosage forms. PMID- 20352529 TI - Quantitative neuroproteomics: classical and novel tools for studying neural differentiation and function. AB - Mechanisms underlying neural stem cell proliferation, differentiation and maturation play a critical role in the formation and wiring of neuronal connections. This process involves the activation of multiple serial events, which guide the undifferentiated cells to different lineages via distinctive developmental programs, forming neuronal circuits and thus shaping the adult nervous system. Furthermore, alterations within these strictly regulated pathways can lead to severe neurological and psychiatric diseases. In this framework, the investigation of the high dynamic protein expression changes and other factors affecting protein functions, for example post-translational modifications, the alterations of protein interaction networks, is of pivotal importance for the understanding of the molecular mechanisms responsible for cell differentiation. More recently, proteomic studies in neuroscience ("neuroproteomics") are receiving increased interest for the primary understanding of the regulatory networks underlying neuronal differentiation processes. Besides the classical two dimensional-based proteomic strategies, the emerging platforms for LC-MS shotgun proteomic analysis hold great promise in unraveling the molecular basis of neural stem cell differentiation. In this review, recent advancements in label-free LC MS quantitative neuroproteomics are highlighted as a new tool for the study of neural differentiation and functions, in comparison to mass spectrometry-based labeling approaches. The more commonly used protein profiling strategies and model systems for the analysis of neural differentiation are also discussed, along with the challenging proteomic approaches aimed to analyze the nervous system-specific organelles, the neural cells secretome and the specific protein interaction networks. PMID- 20352532 TI - Novel application of MRI technique combined with flow-through cell dissolution apparatus as supportive discriminatory test for evaluation of controlled release formulations. AB - Dissolution studies cannot distinguish phenomena occurring inside the dosage forms when studying formulation with similar dissolution profiles-such formulations can behave differently when considering their physical changes. The application of flow-through dissolution apparatus integrated with magnetic resonance imaging (MRI) system for discriminative evaluation of controlled release dosage forms with similar dissolution profiles was presented. Hydrodynamically balanced systems (HBS) containing L: -dopa and various grades hydroxypropyl methylcelluloses were prepared. The dissolution studies of L: -dopa were performed at high field (4.7 T) MR system with MR-compatible flow-through cell. MRI was done with 0.14 x 0.14 x 1-mm spatial resolution and temporal resolution of 10 min to record changes of HBS parameters during dissolution in 0.1 M HCl. Structural and geometrical changes were evaluated using the following parameters: total area of HBS cross-section, its Feret's diameter, perimeter and circularity, area of hydrogel layer, and "dry core" area. While the dissolution profiles of L: -dopa were similar, the image analysis revealed differences in the structural and geometrical changes of the HBS. The mechanism of drug release from polymeric matrices is a result of synergy of several different phenomena occurring during dissolution and may differ between formulations, yet giving similar dissolution profiles. A multivariate analysis was performed to create a model taking into account dissolution data, data from MRI, information about chemical structure, and polymer viscosity. It provided a single model for all the formulations which was confirmed to be competent. The presented method has merit as a potential Process Analytical Technology tool. PMID- 20352533 TI - Preparation and physicochemical characterization of amoxicillin beta-cyclodextrin complexes. AB - Amoxicillin (AMOX), a penicillin A, belongs to the beta-lactam family It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Its beta lactamase degradation might be prevented by using a molecular [AMOX:beta-CD] complex. The aim of this work was to prepare complexes using two methods and then characterize interactions between AMOX and the native beta-CD. The extent of complexation in solution has been evaluated by high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and 2D rotating-frame Overhauser enhancement spectroscopy (2D ROESY). Mass changes (TG), calorimetric effects (DSC), and mass spectrometry (MS) were determined on the same sample under identical conditions using the Skimmer coupling system. Skimmer and infrared spectroscopy (FT-IR) were used to characterize the solid state of the binary system. Complexation of AMOX with beta-CD was proven by FT-IR, NMR, DSC, and HPLC. The 2D ROESY spectra did not show any dipolar proton interaction of the AMOX with cyclodextrin. The 1:1 stoichiometry of the complex was obtained by HPLC. The stability constant for AMOX with beta-CD was determined to be 1,878 M( 1). In the [AMOX:beta-CD] complex, the phenyl group is included inside the beta CD, and the ionized carboxyl group on the penam ring forms hydrogen bonds with the secondary hydroxyl groups of another beta-CD to keep the complex stable. Preparation methods allowed exactly the same complex. PMID- 20352534 TI - Preparation and enhanced oral bioavailability of cryptotanshinone-loaded solid lipid nanoparticles. AB - In this study, solid lipid nanoparticles (SLNs) were successfully prepared by an ultrasonic and high-pressure homogenization method to improve the oral bioavailability of the poorly water-soluble drug cryptotanshinone (CTS). The particle size and distribution, drug loading capacity, drug entrapment efficiency, zeta potential, and long-term physical stability of the SLNs were characterized in detail. A pharmacokinetic study was conducted in rats after oral administration of CTS in different SLNs, and it was found that the relative bioavailability of CTS in the SLNs was significantly increased compared with that of a CTS-suspension. The incorporation of CTS in SLNs also markedly changes the metabolism behavior of CTS to tanshinone IIA. These results indicate that CTS absorption is enhanced significantly by employing SLN formulations, and SLNs represent a powerful approach for improving the oral absorption of poorly soluble drugs. PMID- 20352535 TI - A design and evaluation of layered matrix tablet formulations of metoprolol tartrate. AB - The aim of this paper was to evaluate the performance of different swellable polymers in the form of layered matrix tablets to provide controlled therapeutic effect of metoprolol tartrate for twice daily administration. Seven different swellable polymers (carrageenan, hydroxypropylmethyl cellulose, pectin, guar gum, xanthan gum, chitosan, and ethyl cellulose) were evaluated alone or in combination as release-retardant layer. Tablets were tested for weight variation, hardness, diameter/thickness ratio, friability, and drug content uniformity and subjected to in vitro drug-release studies. In addition, the target-release profile of metoprolol tartrate was plotted using its clinical pharmacokinetic data, and the release profiles of the tablets were evaluated in relation to the plotted target release profile. Carrageenan was determined as the best polymer in two-layered matrix tablet formulations due to its better accordance to the target release profile and was selected for preparing three-layered matrix tablets. Carrageenan formulations exhibited super case II release mechanism. Accelerated stability testing was performed on two- and three-layered matrix tablet formulations of carrageenan. The tablets were stored at 25 degrees C/60% relative humidity and 40 degrees C/75% relative humidity for 6 months and examined for physical appearance, drug content, and release characteristics. At the end of the storage time, formulations showed no change either in physical appearance, drug content, or drug-release profile. These results demonstrated the suitability of three-layered tablet formulation of carrageenan to provide controlled release and improved linearity for metoprolol tartrate in comparison to two-layered tablet formulation. PMID- 20352536 TI - Polymer percolation threshold in HPMC extended release formulation of carbamazepine and verapamil HCl. AB - The principles of the percolation theory were applied to further understand and design hydroxypropyl methylcellulose (HPMC) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the hydration and drug release of hydrophilic matrices allows describing the changes in hydration and drug release kinetics of swellable matrices. The aim of this work was to study and develop extended release matrix formulations for carbamazepine and verapamil HCl, containing hypromellose (HPMC, METHOCEL Premium K100M CR) as rate controlling polymer using the concepts of percolation theory. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, avoiding to formulate in the nearby of the percolation threshold, which will result in a lower variability. Therefore these formulations will be more robust when they are prepared at industrial scale. The HPMC percolation threshold for drugs with very different water solubilities was determined and it was shown that there was no significant influence of drug solubility on the HPMC critical concentration threshold (excipient percolation threshold). This may be related to the versatility and broad functionality of the swelling hydrophilic matrices. PMID- 20352538 TI - Online monitoring of PLGA microparticles formation using Lasentec focused beam reflectance (FBRM) and particle video microscope (PVM). AB - Knowledge of the effects of different product and process variability on microparticle characterization is essential for the successful development, optimization, and scale-up of an encapsulation process. In the current research, the qualitative application of the Lasentec focused beam reflectance (FBRM) system for online monitoring of microparticle size distribution was demonstrated. lasentec particle vision and measurement (PVM) images were also employed to follow up the steps of microparticle formation and ripening. The drug entrapment efficiency and drug release characteristics were found to be dependent on the polymer, drug, and surfactant concentrations. DSC, FTIR, and XRD data revealed that the drug was compatible with the matrix forming polymer in the solid state. As indicated from the chord count data, FBRM was sensitive to the amount of the solid materials and the number of microparticles formed. Linear relationships with good correlations were obtained between polymer, drug, and surfactant levels and the disappearance rate of 5 to 36.8, 18.4 to 135.9, and 63 to 398 microm chord length fractions. Upon organic solvent evaporation, PVM imaging detected various stages of microemulsion droplets, sheath formation, and solidification with subsequent microparticle hardening. This study illustrated the utility of FBRM and PVM in monitoring the progress of particle formation during drug encapsulation. PMID- 20352537 TI - An electronic tongue: evaluation of the masking efficacy of sweetening and/or flavoring agents on the bitter taste of epinephrine. AB - An epinephrine (E) tablet is under development for sublingual (SL) administration for the first-aid treatment of anaphylaxis; however, the inherent bitterness of E may hinder acceptability by patients, especially children. To assess the degree of E bitterness and to predict the masking effects of sweetening and/or flavoring non-medicinal ingredients (NMIs), the potential usefulness of an electronic tongue (e-Tongue) was evaluated. The e-Tongue sensors were conditioned, calibrated, and tested for taste discrimination. Six standard active pharmaceutical ingredients were used to build and validate a bitterness model which was then used to assess E bitartrate (EB) solutions from 0.3-9 mM. Taste masking efficiency of aspartame (ASP), acesulfame potassium (ASK), and citric acid (CA) each at 0.5 mM was evaluated. Using EB 9 mM, the bitterness score was 20 on a scale of 20 (unacceptable) down to 1 (not detected). When NMIs 0.5 mM were added, neither ASK (17.2, unacceptable) nor was ASP (14.0, limit acceptable) effective in masking the bitter taste. When the combination of ASK and ASP was used, the bitterness score was reduced to 9.2 (acceptable). However, the addition of CA alone resulted in the best reduction of the bitterness score to 3.3 (not detected). Using the e-Tongue, the incorporation of a variety of sweetening and/or flavoring NMIs into a SL tablet of E could be shown to mask its bitter taste by up to 80%. These results should be confirmed by in vivo studies. PMID- 20352539 TI - Hemodialysis complications of hydroxocobalamin: a case report. AB - Hydroxocobalamin is a new antidote approved by the FDA for the treatment of cyanide poisoning. Our report describes a patient with cyanide poisoning who survived after treatment with hydroxocobalamin and complications we encountered with hemodialysis. A 34-year-old female presented to the emergency department after a syncopal event and seizures. Her systolic blood pressure was 75 mmHg, her QRS complex progressively widened, and pulses were lost. She was intubated and resuscitated with fluids, sodium bicarbonate for her QRS widening and vasopressors. Venous blood gas demonstrated a pH of 6.36 with an O2 saturation of 99%. Due to the acidemia with a normal pulse oximetry, simultaneous venous and arterial blood gases were obtained. Venous gas demonstrated a pH of 6.80 with a PO2 of 222 mmHg, an O2 saturation of 99%. The arterial blood gas showed a pH of 6.82, a PO2 518 mmHg, an O2 saturation of 100%. Cyanide was suspected and hydroxocobalamin and sodium thiosulfate were given. Within 40 min of hydroxocobalamin administration, vasopressors were discontinued. Initially, nephrology attempted dialysis for metabolic acidosis; however, the dialysis machine repeatedly shut down due to a "blood leak". This was an unforeseen effect attributed to hydroxocobalamin. Cyanide level, drawn 20 min after the antidote was completed, was elevated at 22 mcg/dL. Her urinary thiocyanate level could not be analyzed due to an "interfering substance". Hydroxocobalamin is an effective antidote. However, clinicians must be aware of its effects on hemodialysis machines which could delay the initiation of this important treatment modality in the severely acidemic patient. PMID- 20352540 TI - Octreotide's role in the management of sulfonylurea-induced hypoglycemia. AB - The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia. PMID- 20352541 TI - Case files of the California poison control system, San Francisco division: blue thunder ingestion: methanol, nitromethane, and elevated creatinine. PMID- 20352542 TI - Daily fluctuations in teachers' well-being: a diary study using the Job Demands Resources model. AB - The study tests the dynamic nature of the Job Demands-Resources model with regard to both motivational and health impairment processes. It does so by examining whether daily fluctuations in co-workers' support (i.e., a typical job resource) and daily fluctuations in work/family conflict (i.e., a typical job demand) predict day-levels of job satisfaction and mental health through work engagement and exhaustion, respectively. A total of 61 schoolteachers completed a general questionnaire and a daily survey over a period of five consecutive work days. Multilevel analyses provided evidence for both the above processes. Consistently with the hypotheses, our results showed that day-level work engagement mediated the impact of day-level co-workers' support on day-level job satisfaction and day level mental health, after general levels of work engagement and outcome variables had been controlled for. Moreover, day-level exhaustion mediated the relationship between day-level work/family conflict and day-level job satisfaction and day-level mental health after general levels of exhaustion and outcome variables had been controlled for. These findings provide new insights into the dynamic psychological processes that determine daily fluctuations in employee well-being. Such insights may be transformed into job redesign strategies and other interventions designed to enhance work-related psychological well-being on a daily level. PMID- 20352543 TI - The future of behavioral sleep medicine: a report on consensus votes at the Ponte Vedra Behavioral Sleep Medicine Consensus Conference, March 27-29, 2009. AB - On March 27 through 29, 2009 a consensus conference was held to address a series of issues and propositions related to clinical practice, research, and education in behavioral sleep medicine (BSM). The conference, held in in Ponte Vedra, Florida, included presentations given by key opinion leaders regarding the past and future of BSM, discussion panels and work groups, and anonymous voting on a slate of propositions. There was broad consensus that certification in sleep medicine (i.e., American Board of Sleep Medicine or American Board of Medical Specialties) does not confer automatic expertise in BSM; clinicians without certification in BSM (CBSM) should not be able to supervise BSM cases to fulfill CBSM eligibility requirements; psychologists should pursue independent board certification in BSM by the American Board of Professional Psychology; no program should receive an American Academy of Sleep Medicine "Academic Program of Distinction" designation, unless they have a CBSM professional on staff; sleep disorder center accreditation requirements should include the availability of BSM services from a CBSM provider; an annual or biannual BSM conference should be convened; an independent Society of Behavioral Sleep Medicine should be established; and the new society's journal should be Behavioral Sleep Medicine. PMID- 20352544 TI - The future of behavioral sleep medicine: a report on the presentations given at the Ponte Vedra Behavioral Sleep Medicine Consensus Conference, March 27-29, 2009. AB - A major goal of the Behavioral Sleep Medicine Consensus Conference held in Ponte Vedra, Florida on March 27 through 29, 2009 was to have 15 key opinion leaders provide the latest information on their areas of expertise. Those leaders represented the breadth of the behavioral sleep medicine field (pediatrics, adults, insomnia, PAP adherence, and circadian rhythm disorders) and included clinicians and researchers from a variety of settings (academia, private practice, the military, and primary care). The presentations highlighted the milestones already achieved by the field (critical mass, solid empirical base, 30+ training programs, certification, dedicated journal, and dedicated textbook), as well as important future directions (more clinical research, public relations campaigns, training, and reimbursement). PMID- 20352545 TI - Subtypes of sleep disturbance: associations among symptoms, comorbidities, treatment, and medical costs. AB - Medical claims and survey data were used to evaluate patients with sleep disturbance lasting 1 year or more, and to identify subtypes of sleep disturbance using latent class analysis. Four subtypes were identified from the 1,374 patients. Subtypes differed on the number of sleep disturbance symptoms, presence of non-restorative sleep and comorbidities, degree of daytime impairment, and insomnia severity. The results from this study suggest that patient-reported symptoms of sleep disturbance, the frequency of symptoms, functional impairment, and comorbid conditions are important elements in distinguishing among groups of patients with varying degrees of sleep problems. These data provide evidence that the Insomnia Severity Index (ISI) varies accordingly with the frequency and resulting impairment of symptoms captured in the 4 clusters. PMID- 20352546 TI - Personalized feedback to improve CPAP adherence in obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is effectively treated with continuous positive airway pressure (CPAP). Low rates of CPAP adherence led to the development of a personalized feedback intervention requiring minimal provider burden. In a comparison of the intervention to standard information, group differences failed to reach significance. Explanations for the findings include low power, that machines were not provided, and an atypical sample. Effect sizes were medium to large at 2 weeks, suggesting that sufficiently powered studies may be warranted. PMID- 20352547 TI - Association between sleep hygiene and sleep quality in medical students. AB - The aim of this study was to determine whether subjective sleep quality was reduced in medical students, and whether demographics and sleep hygiene behaviors were associated with sleep quality. A Web-based survey was completed by 314 medical students, containing questions about demographics, sleep habits, exercise habits, caffeine, tobacco and alcohol use, and subjective sleep quality (using the Pittsburgh Sleep Quality Index). Correlation and regression analyses tested for associations among demographics, sleep hygiene behaviors, and sleep quality. As hypothesized, medical students' sleep quality was significantly worse than a healthy adult normative sample (t = 5.13, p < .001). Poor sleep quality in medical students was predicted by several demographic and sleep hygiene variables, and future research directions are proposed. PMID- 20352548 TI - Male and female genital cutting among Southern Thailand's Muslims: rituals, biomedical practice and local discourses. AB - This paper explores how local people in a province in southern Thailand perceive the practice of male and female genital cutting. In order to understand the importance placed on these practices, a comparison is drawn between the two and also between the male circumcision and the Buddhist ordination of monks as rites of passage. Discourses on the exposure or concealment of male and female bodies, respectively, witness to the relevance of both the local political-historical context and biomedical hegemony to gendered bodies. The comparisons evince the need to reflect upon the theoretical and ethical implications of studying genital cutting and focusing exclusively on one of the two practices rather than, as this paper claims to be necessary, considering them as inextricably connected. PMID- 20352549 TI - Identification, mycotoxin risk and pathogenicity of Fusarium species associated with fig endosepsis in Apulia, Italy. AB - In a survey carried out on 87 rotted fig fruits samples collected in the Apulia region of Italy, the authors isolated 126 Fusarium strains identified as F. ramigenum (69 strains), F. solani (49), F. proliferatum (five) and three not identified. Investigation on the fertility of the strains belonging to F. proliferatum and F. ramigenum revealed that only strains of F. proliferatum were fertile. The identity of F. ramigenum strains was confirmed by sequencing a portion of the translation elongation factor-1alpha gene. When Fusarium species were analysed for their toxigenicity, 37/69 strains of F. ramigenum produced fusaric acid (FA) up to 525 mg kg(-1); 30 strains produced beauvericin (BEA) up to 190 mg kg(-1); 60 strains produced fumonisin B(1) (FB(1)) and fumonisin B(2) (FB(2)) up to 1575 mg kg(-1) of total FBs; and two strains produced fusaproliferin (FUP) up to 345 mg kg(-1); all five strains of F. proliferatum produced FA at low levels; two strains produced BEA up to 205 mg kg(-1); one strain produced FB(1) and FB(2), 1100 and 470 mg kg(-1), respectively; and one strain produced FUP, 820 mg kg(-1); F. solani (30 strains) produced FA, 13 strains up to 215 mg kg(-1). Few fungal extracts showed high toxicity toward brine shrimp larvae and in some cases in relation to BEA and FA content. A pathogenic assay on fig fruits showed that all three species were pathogenic, with higher virulence of F. ramigenum. These data report for the first time the production of BEA and FB(1)/FB(2) by F. ramigenum and show that it is a main agent of fig endosepsis in Apulia and can contribute to fumonisin contamination of fresh and dried figs. PMID- 20352550 TI - Exposure to particulate air pollution at different living locations and respiratory symptoms in Hong Kong--an application of satellite information. AB - Respiratory ill-health effects due to particulate air exposure at different geographical locations in Hong Kong that aggregate individual living locations were estimated based on satellite information. We assessed the presence of respiratory symptoms of a frequent cough or sputum in school students aged 11-20 years old (n = 9,881). Daily particulate air pollution levels at students' living locations were derived from the surface extinction coefficients measured by satellite and measurements from the air pollutant monitoring stations at ground level. Adjusted odds ratio (OR) [95% CI] of respiratory symptoms was 1.047 [1.005, 1.091] per 10 microg m(-3) increase in PM(10) concentration. Specificity tests showed that adjusted OR of having other symptoms is not significant (p = 0.20-0.94). Exposures to PM(10) at different geographical locations is associated with increased odds of having respiratory symptoms (cough or sputum) but not with other symptoms unrelated to air pollution. PMID- 20352551 TI - Situational factors associated with road traffic crashes: a case-control study on the Yaounde-Douala road section, Cameroon. AB - Our aim was to identify situational factors associated with road traffic crash sites on a heavy traffic 243 km road section in Cameroon. We conducted a case control study on Yaounde-Douala road section. Cases were sites where an injury crash was reported to one of the 13 police stations on this road section over a period from 2004 to 2007. Control sites were randomly selected on same road section where no crash was reported. A total of 474 crash sites and 509 control sites were included. Results showed statistically significant associations with injury crash risk for flat road profile (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI) = 1.15-2.01), irregular road surface conditions (aOR = 1.43, 95% CI = 1.04-1.99), roadside obstacle situated less than 4 m from the road edge (aOR = 1.99, 95% CI = 1.09-3.63), three-legged intersections (aOR = 3.11, 95% CI = 1.15-8.39) and four-legged intersections (aOR = 3.23, 95% CI = 1.15 6.92). Built-up areas were significantly associated with injury crash sites where verge depth was 0 m (aOR = 2.33; 95% CI = 1.97-2.77). Our results suggest that traffic calming and speed enforcement measures in built-up areas, intersections and on flat sections of this road should be strongly encouraged. PMID- 20352552 TI - An integrated surveillance system of road traffic injuries in the Lazio region of Italy: results of a 5-year study (2001-2005). AB - Road traffic injuries represent a relevant public-health problem. In the Lazio region of Italy, a surveillance system was activated. The aim of this work is to describe the surveillance system and report the health information in terms of temporal trends for the 5-year period 2001-2005. We identified all emergency department (ED) visits in the emergency database and then linked them with hospital discharges and mortality registry. From the integrated database, we calculated the rates of emergency room visits, of hospital admissions, and of mortality, reporting the temporal trends. Between 2001 and 2005 the rate of ED visits was 3151 per 100,000 inhabitants. Hospitalisation rates showed a significant decreasing trend. The surveillance identified 22% more deaths in the study period than reported by the official statistics. The surveillance revealed a decreasing trend for hospital admissions and a decline in deaths in 2003 concurrent to the introduction of the driver's licence point system. PMID- 20352553 TI - Alcohol-associated injury visits to emergency departments in Pasto, Colombia in 2006. PMID- 20352554 TI - Cognitive and emotional factors associated with elective breast augmentation among young women. AB - The purpose of this research was to propose and evaluate a psychosocial model of young women's intentions to obtain breast implants and the preparatory steps taken towards having breast implant surgery. The model integrated anticipated regret, descriptive norms and image norms from the media into the theory of planned behaviour (TPB). Focus groups (n = 58) informed development of measures of outcome expectancies, preparatory steps and normative influence. The model was tested and replicated among two samples of young women who had ever considered getting breast implants (n = 200, n = 152). Intentions and preparatory steps served as outcomes. Model constructs and outcomes were initially assessed; outcomes were re-assessed 11 weeks later. Evaluative attitudes and anticipated regret predicted intentions; in turn, intentions, along with descriptive norms, predicted subsequent preparatory steps. Perceived risk (susceptibility, severity) of negative medical consequences of breast implants predicted anticipated regret, which predicted evaluative attitudes. Intentions and preparatory steps exhibited interplay over time. This research provides the first comprehensive model predicting intentions and preparatory steps towards breast augmentation surgery. It supports the addition of anticipated regret to the TPB and suggests mutual influence between intentions and preparatory steps towards a final behavioural outcome. PMID- 20352556 TI - Katharine O'Connell White, M.D., M.P.H., F.A.C.O.G. PMID- 20352557 TI - Update on contraception. PMID- 20352558 TI - Emergency contraception: update and review. AB - Emergency contraception (EC) is the postcoital method of pregnancy prevention. Three methods of EC are used in the United States: (1) levonorgestrel-only pills, Plan B (Barr Pharmaceuticals, LLC, New Jersey) (2) combined estrogen and progestin pills, and (3) the copper intrauterine device. Used within 120 hours after unprotected sexual intercourse, EC reduces the risk of pregnancy by 60 to 94%. EC is a critical component of medical care for sexual assault survivors, and several states have laws mandating this standard of care. Levonorgestrel-only EC is available to women >or=17 years of age without a prescription. Women who were counseled by their clinician about EC were 11 times more likely to use EC in the following 12 months. Advance provision of EC to women has not been found to decrease rates of unintended pregnancy compared with routine pharmacy access; however, women routinely prefer advance provision. The newly approved by the Food and Drug Administration single-dose EC, Plan B One-Step (Barr Pharmaceuticals, LLC), may affect unintended pregnancy rates among EC users by simplifying use. PMID- 20352559 TI - Transcervical sterilization. AB - Sterilization is frequently chosen as a method of permanent contraception. Traditional approaches involve surgery under anesthesia in an operating room and are associated with a recovery period and scars. Transcervical sterilization is an incision-free, minimally invasive approach to sterilization. When compared with laparoscopic surgery, transcervical hysteroscopic sterilization does not need to be performed in an operating room, requires less anesthesia, has a shorter recovery period, and is more cost effective. The Essure Permanent Birth Control System (Conceptus, Inc., Mountain View, CA) and Adiana Permanent Contraception System (Hologic, Inc., Bedford, MA) are two available hysteroscopic sterilization techniques. They cause fibrosis and tubal occlusion over a 3-month period so women must use an alternative form of contraception during the first 3 months. A 3-month hysterosalpingogram confirms successful placement and tubal occlusion. Transcervical sterilization is similarly effective to other sterilization methods and is satisfactory to women. PMID- 20352560 TI - Contraceptive implants. AB - Implantable contraception has been extensively used worldwide. Implants are one of the most effective and reversible methods of contraception available. These devices may be particularly appropriate for certain populations of women, including women who cannot use estrogen-containing contraception. Implants are safe for use by women with many chronic medical problems. The newest implant, Implanon (Organon International, Oss, The Netherlands), is the only device currently available in the United States and was approved in 2006. It is registered for 3 years of pregnancy prevention. Contraceptive implants have failure rates similar to tubal ligation, and yet they are readily reversible with a return to fertility within days of removal. Moreover, these contraceptive devices can be safely placed in the immediate postpartum period, ensuring good contraceptive coverage for women who may be at risk for an unintended pregnancy. Irregular bleeding is a common side effect for all progestin-only contraceptive implants. Preinsertion counseling should address possible side effects, and treatment may be offered to women who experience prolonged or frequent bleeding. PMID- 20352561 TI - Intrauterine contraceptives: a review of uses, side effects, and candidates. AB - This article reviews the two intrauterine devices (IUDs) available in the United States: the TCu380A, marketed as ParaGard (Duramed Pharmaceuticals, Inc. Pomona, NY), and the levonorgestrel-releasing intrauterine system (LNG-IUS), marketed as Mirena (Bayer HealthCare Pharmaceuticals, Inc., Wayne, NJ). The properties of the two devices are detailed, as well as noncontraceptive indications and appropriate candidates for use. Studies consistently demonstrate that the devices are safe, effective, and provide cost savings when compared with other reversible methods. The TCu380A may be used as postcoital contraception with close to 100% effectiveness. Menstrual blood loss is likely to increase with the TCu380A and decrease with the LNG-IUS. Reduction in menstrual blood loss and endometrial suppression make the LNG-IUS an increasingly popular treatment for menorrhagia, endometriosis, adenomyosis, and as an adjunct to estrogen therapy. IUDs may be inserted immediately after a first- or second-trimester abortion, immediately postpartum, and >or=4 weeks postpartum. Candidacy for IUDs has expanded, and includes nulliparous women, adolescents, and women with immunocompromised conditions including HIV. PMID- 20352562 TI - Injectable contraception. AB - Injectable contraception has many advantages and is a popular birth control method worldwide. Its efficacy is independent of a daily action or an intervention around the time of coitus. It is highly efficacious and well tolerated in general. In the United States, the available injectable contraceptive is depot medroxyprogesterone acetate (DMPA). Its use is associated with a decrease in bone mineral density (BMD) that is largely if not completely reversible over time and very comparable to the BMD loss associated with pregnancy and breastfeeding. The available knowledge on the impact of BMD loss on the risks of fractures later in life is incomplete, but in the light of the small magnitude of impact of DMPA on BMD and its reversibility, any increase in the risk of osteoporotic fractures is likely to be small. This article reviews the recent evidence on DMPA's efficacy, risks and benefits, and side effects with a focus on bone health issues. PMID- 20352563 TI - The contraceptive vaginal ring. AB - The contraceptive vaginal ring offers effective contraception that is self administered, requires less frequent dosing than many other forms of contraception, and provides low doses of hormones. NuvaRing (Organon, Oss, The Netherlands), the only contraceptive vaginal ring approved for use in the United States, contains etonogestrel and ethinyl estradiol. It is inserted into the vagina for 3 weeks, followed by a 1-week ring-free period, and works by inhibiting ovulation. Most women note a beneficial effect on bleeding profiles and are satisfied with NuvaRing. Commonly reported adverse events include vaginitis, leukorrhea, headaches, and device-related events such as discomfort. Serious adverse events are rare. In Chile and Peru, progesterone-only vaginal contraceptive rings are available for nursing women. Studies are ongoing examining new formulations of vaginal contraceptive rings. PMID- 20352564 TI - Obesity and contraception: emerging issues. AB - Obesity is increasing in prevalence worldwide. Obese women are at similar risk of unintended pregnancy as normal weight women, although limited data are available on the effects of obesity on the efficacy of contraception. Conflicting data exist regarding efficacy of oral contraceptives in obese women, although trends of oral contraceptive failure are no higher than compared with those of normal weight women. The risk of venous thromboembolism is increased with obesity, and this risk may be additive when using a combined hormonal method. Bariatric surgery can lead to increased fertility; postoperative recommendations include avoiding pregnancy in the first year. Contraceptive use patterns in these women are largely unknown. Surgeons need greater awareness of the need for use of effective long-acting methods, and consensus guidelines need to be established. PMID- 20352565 TI - [Simulation and air-conditioning in the nose]. AB - Heating and humidification of the respiratory air are the main functions of the nasal airways in addition to cleansing and olfaction. Optimal nasal air conditioning is mandatory for an ideal pulmonary gas exchange in order to avoid dessication and adhesion of the alveolar capillary bed. The complex three dimensional anatomical structure of the nose makes it impossible to perform detailed in vivo studies on intranasal heating and humidification within the entire nasal airways applying various technical set-ups. The main problem of in vivo temperature and humidity measurements is a poor spatial and time resolution. Therefore, in vivo measurements are feasible to a restricted extent, only providing single temperature values as the complete nose is not entirely accessible. Therefore, data on the overall performance of the nose are only based on one single measurement within each nasal segment. In vivo measurements within the entire nose are not feasible. These serious technical issues concerning in vivo measurements led to a large number of numerical simulation projects in the last few years providing novel information about the complex functions of the nasal airways. In general, numerical simulations only calculate predictions in a computational model, e. g. realistic nose model, depending on the setting of the boundary conditions. Therefore, numerical simulations achieve only approximations of a possible real situation. The aim of this report is the synopsis of the technical expertise on the field of in vivo nasal air conditioning, the novel information of numerical simulations and the current state of knowledge on the influence of nasal and sinus surgery on nasal air conditioning. PMID- 20352566 TI - [Nasal surgery in patients with systemic disorders]. AB - Systemic disorders represent a heterogenous group of diseases which can primarily manifest at the nose and sinuses as limited disease or secondarily as part of the systemic involvement. Rhinologists therefore play an important role in the diagnostic but also therapeutic process. Although therapy of systemic disorders is primary systemic, additional nasal surgery may become necessary. Surgical procedures include sinus surgery for the treatment of complications of the orbit and the lacrimal duct, septorhinoplasty due to saddle nose deformity and closure of septal perforation. Since many systemic disorders represent very rare diseases, recommendations are based on the analysis of single case reports and studies with a limited number of patients. Even though data is still limited, experiences published so far have shown that autogenous cartilage or bone transplants can be used in nasal reconstruction of deformities caused by tuberculosis, leprosy, wegener's granulomatosis, sarcoidosis and relapsing polychondritis. Experiences gained from these diseases support our observation that well-established techniques of septorhinoplasty can be used in systemic disorders as well. However, reaching a state of remission is an essential condition before considering any rhinosurgery in these patients. Under these circumstances revision surgery has to be expected more frequently compared to the typical collective of patients undergoing septorhinoplasty. These observations in part may also be useful for the treatment of nasal septal perforations since implantation of cartilage- or bone grafts represents an essential step in the closure of septal perforations. Apart from the treatment of orbital complications, sinus surgery has been proven beneficial in reducing nasal symptoms and increasing quality of life in patients refractory to systemic treatment. PMID- 20352567 TI - [Structural grafts and suture techniques in functional and aesthetic rhinoplasty surgery]. AB - Rhinoplasty has undergone important changes. With the advent of the open structure approach, requirements for structural grafting and suture techniques have increased substantially. The present review analyzes the current literature on frequently referenced structural grafts and suture techniques. Individual techniques are described and their utility is discussed and critically reviewed in light of available data. PMID- 20352568 TI - [Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses]. AB - In this review, anatomy and physiology of the respiratory mucosa of nose and paranasal sinuses are summarized under the aspect of its clinical significance. Basics of endonasal cleaning including mucociliary clearance and nasal reflexes, as well as defence mechanisms are explained. Physiological wound healing, aspects of endonasal topical medical therapy and typical diagnostic procedures to evaluate the respiratory functions are presented. Finally, the pathophysiologies of different subtypes of non-allergic rhinitis are outlined together with treatment recommendations. PMID- 20352569 TI - [Quality of life before and after septoplasty and rhinoplasty]. AB - Subjective assessment of quality of life (QOL) as an important aspect of outcomes research has received increasing importance during the past decades. QOL is measured with standardized questionnaires which had been tested with regard to reliability, validity, and sensitivity. Surgical procedures of the nasal septum (septoplasty) and the external nose (rhinoplasty) are frequently performed. Since many years subjectively assessed results of these operations have been reported in the literature. Nevertheless, validated QOL instruments were applied only for one decade. Beforehand, measurements were performed using retrospective assessment of contentment or visual analogue scales. Prospective application of validated disease-specific and general measuring instruments has to be demanded for future studies.Most of the septoplasty patients as well as most of the rhinoplasty patients evaluate the operation being successful. Nevertheless, a relevant number of patients is not satisfied with the result of surgery. In this context, QOL instruments have the potential to identify further factors influencing the outcome. Especially in rhinoplasty patients, special attention has to be drawn on potential psychosocial effects of the operation. PMID- 20352570 TI - [Rhinosurgery in children: developmental and surgical aspects of the growing nose]. AB - The anatomy of the nasal skeleton in newborns and adults are not alike. The complete cartilaginous framework of the neonatal nose becomes partly and gradually ossified during the years of growth and is more vulnerable to trauma in that period. Injury in the early youth may have large consequences for development of a nasal deformity which will increase during growth and reach its peak during and after the adolescent growth spurt. To understand more of the underlying problems of nasal malformations and their treatment (septoplasty) these items became the focus of multiple animal studies in the last 40 years. The effects of surgery on the nasal septum varied considerably, seemingly depending on which experimental animal was used. In review, however, it appeared that the very different techniques of surgery might be even more influential in this respect. Study of one of the larger series of experiments in young rabbits comprised skeletal measurements with statistical analysis and microscopic observations of the tissues. The behaviour of hyaline cartilage of the human nose appeared to be comparable to that of mammals. Cartilage, although resilient, can be easily fractured whereas its tendency to integrated healing is very low, even when the perichondrium has been saved. Also surgical procedures - like in septoplasty - may result in growth disturbances of the nasal skeleton like deviation or nasal spine. Loss of cartilage, as might occur after a septum abscess, is never completely restored despite some cartilage regeneration. In this article the many experimental studies are reviewed and compared. Still there remains a lack of real consensus in the literature concerning the developmental effects of rhinosurgry in children. Based on their observations in animals and a few clinical studies, mostly with small numbers of patients but with a long follow-up, the authors have compiled a list of guidelines to be considered before starting to perform surgery on the growing midface in children. PMID- 20352571 TI - [Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex]. AB - In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP treatment. PMID- 20352572 TI - [Surgery of the turbinates and "empty nose" syndrome]. AB - Surgical therapy of the inferior and/or middle turbinate is indicated when conservative treatment options have failed. The wanted goal is a reduction of the soft tissue volume of the turbinates regarding the individual anatomic findings and simultaneously conserving as much mucosa as possible. As the turbinates serve as a functional entity within the nose they take care of climatisation, moistening and cleaning of the inhaled air. Thus a free nasal breathing means a decent quality of life as well. Regarding the multitude of different surgical techniques we confirm that no ideal standard technique for turbinate reduction has been developed so far. Moreover there is a lack of prospective and comparable long-term studies which makes it difficult to recommend evidence-based surgical techniques. However, the anterior turbinoplasty seems to fulfil the preconditions of limited tissue reduction and mucosa-preservation and therefore it is the method of choice today. Radical resection of the turbinates may lead to severe functional disturbances developing a secondary atrophic rhinitis. The "empty nose" syndrome is a specific entity within the secondary atrophic rhinitis where intranasal changes in airflow result in disturbed climatisation and also interferes with pulmonary function. Results deriving from an actual in vivo study of climatisation and airflow in "empty nose" patients are presented. PMID- 20352573 TI - [The cartilage anchor--a helpful tool for precise control of the nasolabial fold]. AB - The cartilage anchor is a cartilagineous strip inserted subcutaneously in front of the nasolabial fold which allows precise forming and movement of the nasolabial fold in facial palsy. It is taken from ear cartilage. Static and dynamic symmetry can be improved considerably by fixing a free microvascular muscle transplant or a sling plasty to the cartilage anchor. In cases of significant laxity of the paralysed side of the face, the combination of muscle transplant and sling plasty may be helpful. PMID- 20352574 TI - [Gillies and McLaughlin's dynamic muscle support in irreversible facial palsy]. AB - The goals in surgical treatment of unilateral long-standing facial paralysis are individual concepts restoring mimetic function, aesthetic facial symmetry at rest and protection of the eye by complete eyelid closure. Facial reanimation with free neuromuscular flaps is the actual standard treatment. The reanimation of the paralysed eyelid is still a major problem. Gillies described in 1934 his technique using the transposition of the temporal muscle with two strips of its own fascia performing a dynamic support of the upper and lower eyelid. McLaughlin was using the temporal muscle in combination with fascia lata for the reanimation of the oral muscle sling (1953). There are still some indications for these procedures. The long-term follow-up of 93 patients with Gillies procedure and 180 patients with McLaughlin's muscle support gives a sound base for decision making in facial reanimation. PMID- 20352575 TI - Adipose stem cells for soft tissue regeneration. AB - Adipose-derived stem cells (ASCs) can be isolated from human adipose tissue with the exceptional potential for differentiation into mature adipocytes. Utilization of this system is very promising in developing improved techniques to repair soft tissue defects. Current reconstructive procedures, especially after trauma and oncological surgery, transfer autologous soft tissue grafts having limitations. However, ASCs offer the ability to either generate soft tissue with no donor-site morbidity (with the exception of a minor loss of adipose tissue) or enhance the viability and durability of other grafts. This review will discuss the relevant properties of human adult adipose-derived stem cells for the regeneration of adipose tissue. Discussion will focus on the biology of ASCs, cell delivery vehicles/scaffolds useful in applying ASCs as a therapy, and suitable IN VIVO animal models for studying adipose tissue engineering. Also included is a description of the current clinical studies with ASCs in Europe and Asia. PMID- 20352576 TI - [Commentary on the article of Herold et al.: The use of mamma MRI volumetry to evaluate the rates of fat survival after autologous lipotransfer]. PMID- 20352577 TI - [Current perspective and limitations of autologous fat transplantation- "consensus meeting" of the German Society of Plastic, Reconstructive and Aesthetic Surgeons at Hannover; September 2009]. AB - One hundred years after the first description of autologous fat transplantation, this technique is receiving renewed attention. Initially, critically reviewed by plastic surgery societies, particularly those in the United States, the transfer of autologous fat was recently addressed at the September 2009 annual meeting of the German Society of Plastic Reconstructive and Aesthetic Surgeons in Hannover. In this consensus meeting, the panel reviewed both the current status of autologous fat transfer as well as established data concerning this evolving practice. In Germany, autologous fat transplantation is regulated by the Law on Tissue Transfer and Processing (Gewebegesetz). In an effort to facilitate future comparisons it is mandatory to describe harvesting, processing and reinjection techniques in detail. The consensus panel concluded that fat should be harvested using low vacuum settings and then transplanted in thin layers (Evidence V). Quantification of transplanted fat can best be performed by MRI (Evidence level III). Limited clinical studies are available with only some reaching a level of evidence II. At present, risk associated with autologous fat transplantation is considered to be minor. Tumor induction by autologous fat grafting is not proven. New techniques like stem cell enriched fat grafts may offer new promise for the Plastic and Reconstructive Surgeon. PMID- 20352578 TI - [Structural fat grafting for rejuvenation of the dorsum of the hand]. AB - In parallel with aging, increasing skin laxity and subcutaneous atrophy occur in many regions of the human body. Apart from the most obvious facial region, where most aesthetic operations for rejuvenation are done, also the dorsum of the hand is continuously visible in daily life. This region exhibits skin laxity, subcutaneous atrophy and age-related pigmentations in a comparable manner to the face. Autologous transplantation of fatty tissue (structural fat grafting, lipofilling) enables subcutaneous regeneration by refilling the subcutaneous space and hence reducing some of the age-related degenerative process. This paper illustrates the special operative technique on the hand in the form of a case report. Furthermore, 3D surface laser scanning permits an objective evaluation of the permanent volume effect over time. In the presented case a volume effect of 69% of the injected volume was measured after 6 months follow-up time. This amount of injected tissue seems to be integrated as a graft and results in a reduction of subcutaneous atrophy in terms of a true regeneration. Structural fat grafting of the dorsum of the hand is thus a method of regenerative medicine. Together with other methods which reduce the age-related pigmentations, it plays a key role in our treatment concept for rejuvenation of the hand. PMID- 20352580 TI - Headache. PMID- 20352581 TI - The epidemiology of primary headache disorders. AB - Primary headache disorders encompass a heterogeneous group of neurologic disorders that cause recurrent or persistent head pain without any clear underlying cause. The epidemiology of the most common primary headache disorders, tension-type headache and migraine, the most common trigeminal autonomic cephalalgia, cluster headache, as well as chronic daily headache are addressed in this review. The incidence, prevalence, burden, and comorbidities of these disorders are discussed, and the risk factors for progression from episodic to chronic daily headache are also reviewed. PMID- 20352582 TI - Pathophysiology of migraine. AB - Our understanding of migraine pathophysiology is a work in progress. As more is learned about migraine, it seems that the probability of identifying a single unifying explanation for this common disorder becomes less and less. Although the neuroanatomy and elements of pain physiology underlying migraine attacks are probably shared pathophysiologic elements, the emerging complexity of migraine genetics suggests that the acute attack may be the final common expression of more than one type of initiating abnormality. After a brief summary of the neuroanatomic structures involved in the generation of migraine attacks and the traditional theories of migraine, the author focuses on the current understanding of migraine genetics and reviews recent data from the neuroimaging and the neurophysiology of migraine. PMID- 20352583 TI - When and how to investigate the patient with headache. AB - The common complaint of headache usually has a benign cause, most often a primary headache syndrome. The history and neurologic and general physical examinations usually permit a definitive diagnosis. When in doubt, diagnostic testing is indicated. Certain historical and examination findings increase the likelihood of a secondary headache disorder and the need for diagnostic testing. These include (1) recent head or neck injury; (2) a new, worse, worsening, or abrupt onset headache; (3) headache brought on by Valsalva maneuver or cough; (4) headache brought on by exertion; (5) headache associated with sexual activity; (6) pregnancy; (7) headache in the patient over the age of ~50; (8) neurologic findings and/or symptoms; (9) systemic signs and/or symptoms; (10) secondary risk factors, such as cancer or human immunodeficiency virus (HIV) infection. Less worrisome are headaches that wake the patient from sleep at night, always occur on the same side, or show a prominent effect of change in posture on the patient's pain. Diagnostic studies include neuroimaging, cerebrospinal fluid (CSF) examination, and blood tests, which are selected depending on the patient's history and findings. For most patients, the diagnostic test of choice is a magnetic resonance imaging (MRI) brain scan. Computed tomography (CT) of the brain is usually obtained in the setting of trauma or the abrupt onset of headache. CSF examination is useful in diagnosing subarachnoid bleeding, infection, and high and low CSF pressure syndromes. PMID- 20352584 TI - Acute treatment of migraine headaches. AB - Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. PMID- 20352585 TI - Diagnosis and management of chronic daily headache. AB - Chronic daily headache (CDH) is a descriptive term that encompasses multiple headache diagnoses and affects approximately 4% of the general adult population. Chronic daily headache results in significant pain and suffering with substantial impact on quality of life, and enormous economic costs to society. Although most patients with primary CDH suffer from chronic migraine or chronic tension-type headache, other primary and secondary headache disorders can also manifest as a CDH syndrome. For CDH management to succeed, secondary headaches need to be ruled out with proper investigations when judged necessary. If the diagnosis of primary CDH is established, diagnosis of the specific CDH subtype is imperative to institute appropriate treatment. The diagnosis and management of distinct CDH entities, chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua, are the primary forms of CDH and the emphasis of this review. Although, strictly speaking, medication overuse headache is a secondary form of CDH, it is also highlighted in this review given its frequent association with primary CDH. PMID- 20352587 TI - Cluster headache: diagnosis and treatment. AB - Cluster headache is a rare yet exquisitely painful primary headache disorder occurring in either episodic or chronic patterns. The unique feature of cluster headache is the distinctive circadian and circannual periodicity in the episodic forms. The attacks are stereotypic--they are of extreme intensity and short duration, occur unilaterally, and are associated with robust signs and symptoms of autonomic dysfunction. Although the pathophysiology of cluster headache remains to be fully understood, there have been a number of recent seminal observations. To exclude structural mimics, patients presenting with symptoms suggestive of cluster headache warrant at least a brain magnetic resonance imaging (MRI) scan in their work-up. The medical treatment of cluster headache includes acute, transitional, and maintenance prophylaxis. Agents used for acute therapy include inhalation of oxygen, triptans, such as sumatriptan, and dihydroergotamine. Transitional prophylaxis refers to the short-term use of fast acting agents. This typically involves either corticosteroids or an occipital nerve block. The mainstay of prophylactic therapy is verapamil. Yet, other medications, including lithium, divalproex sodium, topiramate, methysergide, gabapentin, and even indomethacin, may be useful when the headache fails to respond to verapamil. For medically refractory patients, surgical interventions, occipital nerve stimulation, and deep brain stimulation remain an option. As the sophistication of functional neuroimaging increases, better insight into the pathophysiological mechanisms that underlie cluster headache is expected. PMID- 20352586 TI - Migraine-associated vertigo: diagnosis and treatment. AB - Migraine-associated vertigo has become a well-recognized disease entity diagnosed based on a clinical history of recurrent vertigo attacks unexplained by other central or peripheral otologic abnormalities, which occurs in the patient with a history of migraine headaches. There is no international agreement on what spectrum of symptoms should be covered under this diagnosis, or what terminology should be used. The headaches and vestibular symptoms of migraine-associated vertigo may not be temporally associated, which often obscures the association. Diagnostic tests usually show nonspecific abnormalities that are also seen in patients with migraine who do not experience vestibular symptoms. Management generally follows the recommended treatment of migraine headaches, and includes dietary and lifestyle modifications and medical treatment with beta blockers, calcium channel blockers, and tricyclic amines. Small case series show that acetazolamide and lamotrigine appear to be more effective for the vertigo attacks than headaches. Vestibular rehabilitation has also been shown to be helpful in several studies. In this review, the epidemiologic and clinical features of the disorder, as well as the current state of knowledge on pathophysiology, diagnostic testing, and treatment are described. PMID- 20352588 TI - Trigeminal autonomic cephalalgias: paroxysmal hemicrania, SUNCT/SUNA, and hemicrania continua. AB - The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that include cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing/cranial autonomic features (SUNCT/SUNA). Hemicrania continua (HC) is often included with this group, although the second edition of The International Classification of Headache Disorders did not link the entities. Trigeminal autonomic cephalalgias are generally characterized by relatively short lasting attacks of severe pain and lateralized associated features including the pain, cranial autonomic symptoms, and where present, migrainous symptoms, such as photophobia. Paroxysmal hemicrania has intermediate duration and intermediate attack frequency. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing has the shortest attack duration and the highest attack frequency. Hemicrania continua has a continuous pain with exacerbations that can include cranial autonomic symptoms as part of the phenotype. The syndromes share much in their pathophysiology and investigation paths; however, their treatment is distinct, so that the accurate differentiation is important for optimal management. PMID- 20352590 TI - Management of migraine headache in the emergency department. AB - Headache is one of the more common reasons for adults to visit an emergency department. Most of these visits are for primary headache disorders, most commonly migraine headache. The authors discuss management options for patients presenting to the emergency department with prolonged, severe, or refractory migraine headaches. Particular attention is given to parenteral treatments and protocols that would not be options as an outpatient. The epidemiology, investigation, and outpatient management of migraine headache are discussed in other articles in this issue. PMID- 20352589 TI - Abrupt-onset severe headaches. AB - Thunderclap headache, a severe headache which is maximal in intensity at onset, is associated with numerous underlying disorders, including subarachnoid hemorrhage, unruptured intracranial aneurysm, cervical artery dissection, cerebral venous sinus thrombosis, stroke, intracranial hemorrhage, reversible cerebral vasoconstriction syndrome, and reversible posterior leukoencephalopathy. After exclusion of all possible causes, thunderclap headache may be considered a primary headache. This review summarizes the diagnostic considerations and clinical approach to thunderclap headache, with particular emphasis on the reversible cerebral vasoconstriction syndromes. PMID- 20352592 TI - [Waiting time for and length of physicianc's consultation define the patient physician interaction: results of a prospective study in 478 patients with chronic viral hepatitis]. AB - BACKGROUND: Little is known about the physician-patient interaction in hepatitis B and C. METHODS: This study by the federal competence network hepatitis analysed the physician-patient interaction using the validated FAPI questionnaire. The questionnaire also contained questions concerning demography and disease characteristics. Of the total 1500 questionnaires sent out, 478 were returned (32 %) (20 % HBV vs. 80 % HCV). RESULTS: The FAPI index of patients with HBV/HCV infection (3.10 +/- 0,99) was lower than that in patients with other internal medicine diseases (3.61 +/- 0.92; n = 148). Women had lower values than men (2.98 vs. 3.25; p = 0.005). Patients with active HBV infection showed higher values than those with HCV infection (3.27 vs. 2.97; p < 0.05). Patients with successfully treated hepatitis B/C had higher values than those with active disease (3.36 vs. 3.02; p = 0.004). The index was lower in patients who waited > 2 weeks for the consultation when compared to those with a shorter wait (2.92 vs. 3.31; p < 0.001) and was also lower in patients who waited > 30 min at the consultation day when compared to those with a shorter wait (2.81 vs. 3.39; p < 0.001). The index gradually increased with the consultation length (2.47 < 10 min vs. 2.79 10 - 15 min vs. 3.21 15 - 30 min vs. 3.82 > 30 min; p < 0.001). The index was higher in patients seen by gastroenterologists (3.43) when compared with general practioners (3.10), internists (3.02) and clinical settings (3.13) (p < 0.05). A good information status was associated with higher FAPI values when compared with a bad information status (3.43 vs. 2.76; p < 0.001). Fibrosis, health insurance and age were not associated with FAPI index (p > 0.2). By multivariate analysis a long consultation, a good information status, patients' patience, short waiting times, and providing contact to a patient support group were independently associated with a high index. CONCLUSIONS: The physician patient interaction in chronic viral hepatitis is worse than in other internal medicine diseases with problems being more pronounced in HCV infection and women when compared to men and HBV infection. Short waiting times and patients' patience ameliorated the interaction as well as the consultation length, the information status of the patient and providing contact to a patient support group. Type of health insurance did not affect either waiting times or physician patient interaction; thus there is no hint for a two-class medicine in this part of hepatology. PMID- 20352593 TI - Splenic rupture following endoscopic polypectomy. AB - A 70-year-old man presented with two medium-sized colon polyps at the office of a gastroenterologist. After endoscopic polypectomy in a hospital, the patient was admitted to another hospital because of collapse and increasing abdominal pain. CT scan revealed hematoperitoneum and splenic subcapsular hematoma. Laparotomy with splenectomy was performed because of extended splenic rupture. The postoperative course was unremarkable except late wound dehiscence. PMID- 20352594 TI - Gastrointestinal stromal tumor in a patient with undiagnosed neurofibromatosis type I: an uncommon cause of extrahepatic cholestasis. AB - In this case report we present a 61-year-old patient with obstructive jaundice. Bile duct obstruction was caused by a tumor at the duodenal papilla and bile flow was restored by a plastic stent. Using endoscopic ultrasound and computed tomography imaging two additional tumors of the same morphology were found in the stomach wall and the pelvic region suggesting a multilocular gastrointestinal stroma tumor (GIST). Diagnosis of GIST was confirmed cytologically from the gastric lesion. Based on typical cutaneous manifestations (cafe-au-lait spots, several tiny dermal neurofibromata and Lisch nodules in the iris), a thus far unidentified neurofibromatosis type I was diagnosed which is known to promote multilocular GIST formation. Tumor resection failed because of cardiac decompensation due to a Takotsubo cardiomyopathy during induction of anesthesia. The patient has been started on imatinib instead and shows so far a stable disease over 6 months. PMID- 20352595 TI - [Mesenteric inflammatory veno-occlusive disease (MIVOD)--an underdiagnosed disease?]. AB - Mesenteric, inflammatory veno-occlusive disease is an entity of unknown incidence and aetiology. Inflammation and necrosis of mesenteric veins leads to severe ischaemic damage of an intestinal segment. The clinical and endoscopic presentation can be ambiguous. However, modern multiphasic contrast-enhanced computed tomography allows early diagnosis, when characteristic features are considered. As local resection is the only known cure with minimal risk of recurrent disease, knowledge of this rare disease entity can spare our patients a risky delay of resection and erroneous therapeutic approaches. PMID- 20352596 TI - [Histopathological diagnose of non-alcoholic and alcoholic fatty liver disease]. AB - Alcoholic fatty liver (AFL) as well as non-alcoholic fatty liver (NAFL) are characterised by deposition of lipids into hepatocytes. The diagnosis of steatosis is made if lipid deposition exceeds 5 % of hepatocytes, in case of more than 50 % it is called "fatty liver". An additional inflammatory reaction, with ballooning of hepatocytes, leads to alcoholic steatohepatitis (ASH) or non alcoholic steatohepatitis (NASH). Both ASH or NASH may lead to fibrosis or cirrhosis. To date in clinical practice it is not possible to differentiate between steatosis and steatohepatitis just on the basis of non-invasive tests. Steatohepatitis is present if, along with steatosis, both inflammatory infiltrates of mixed cells in the small liver lobules and liver cell injury in terms of ballooning can be detected. Liver biopsy represents the "gold standard" for confirming the diagnosis and to determine inflammatory activity and potential fibrosis of fatty liver disease. Indications for biopsy should take into account the possible information and its consequences as compared to expense and complication rate and therefore should be assessed in the clinical context. PMID- 20352597 TI - [Radiofrequency ablation of dysplastic Barret's esophagus]. PMID- 20352598 TI - Glucokinase-activating GCKR polymorphisms increase plasma levels of triglycerides and free fatty acids, but do not elevate cardiovascular risk in the Ludwigshafen Risk and Cardiovascular Health Study. AB - Two strongly correlated polymorphisms located within the gene of the glucokinase regulator protein (GKRP), rs780094 and rs1260326, are associated with increased plasma triglyceride levels and provide a genetic model for the long-term activation of hepatic glucokinase. Because pharmacological glucokinase activators are evaluated for the treatment of diabetes, the aim of the study was to assess if these polymorphisms could provide evidence for an increased cardiovascular risk of long-term glucokinase activation. Therefore, these polymorphisms were tested in 3 500 patients of the Ludwigshafen Risk and Cardiovascular Health study, which was designed to assess cardiovascular risk factors. The two variants were associated with a significant increase of both plasma triglycerides (p<0.0001) and VLDL triglyceride levels (p<0.0001). Plasma free fatty acid concentrations were also significantly elevated (p<0.0078). LDL and HDL cholesterol levels were unchanged. No association was found with respect to coronary stenosis, myocardial infarction, left ventricular wall hypertrophy, and hypertension. In conclusion, long-term genetic glucokinase activation by the GKRP polymorphisms was not associated with an increased cardiovascular risk in the study population. PMID- 20352599 TI - Etomidate unmasks intraadrenal regulation of steroidogenesis and proliferation in adrenal cortical cell lines. AB - To characterize intraadrenal adaptations for inhibition of cortisol synthesis, we analyzed the effects of etomidate (ETO) on steroid hormone secretion and expression of key regulators of steroidogenesis and proliferation in human NCI h295 adrenocortical cancer cells. Etomidate potently blocked 11beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and side chain cleavage enzyme (CYP11A1). This inhibition of steroidogenesis was associated with increased expression of steroidogenic acute regulatory protein (StAR), and CYP11A1 and 17alpha-hydroxylase/17, 20-lyase (CYP17A1) protein levels, but not of the respective mRNA levels. Promoter activity of CYP11A1 and melanocortin 2 receptor (MC2R) was not increased by etomidate in treated cells compared to controls. The increase in protein levels was partially reversed by cycloheximide suggesting post-transcriptional mechanisms but also protein stabilization as underlying cause. Furthermore, ETO exhibited antiproliferative activity paralleled by a decrease in phosphorylation of MEK and ERK1, 2. In summary, ETO exhibits pleiotropic effects on adrenal function in vitro. Inhibition of steroidogenesis is followed by increased levels of steroidogenic key proteins and reduced proliferation. These changes reflect adaptations to maintain steroidogenesis at the cost of adrenal proliferation. PMID- 20352600 TI - Centrally administered neuromedin S inhibits feeding behavior and gastroduodenal motility in mice. AB - Neuromedin S (NMS) was recently identified as an endogenous ligand for the FM 4/TGR-1 receptor in the rat hypothalamus. No previous studies have examined the effect of NMS on gut motility. We examined the effects of intracerebroventricular administration of NMS on food intake in food-deprived and free-feeding mice, and on gastroduodenal motility by using a manometric method, and gastric emptying in mice. We found that NMS decreased food intake and the gastric emptying rate. It also disrupted the motor activity in the antrum and duodenum of conscious food deprived mice. These results suggest that NMS influences gut motility as well as feeding behavior. PMID- 20352602 TI - Interdural epidermoid of the cavernous sinus. PMID- 20352601 TI - [Brachytherapy in combination with function-preserving surgery of cancer of the paranasal sinus]. AB - BACKGROUND: Prognosis of patients with advanced/recurrent cancer of paranasal sinuses and orbit with infiltration of the skull base is very bad. Radical surgery does not improve prognosis. A disadvantage of the radical surgery is the functional loss and the residual cosmetic defect. We present the results of a function-preserving surgery in combination with interstitial, image adapted brachytherapy (IABT) for the treatment of these cancers. METHODS AND PATIENTS: Ten patients with paranasal sinus cancer and 16 patients with sarcomas (n=26) were retrospectively analysed. After a maximum tumor resection (mostly R1-R2 resections), 2-12 flexible afterloading plastic tubes were implanted. The postoperative IABT total dose was 10-25 Gy in 2.5 Gy fractions twice daily fractions for 5 days. RESULTS: In all cases the eye was obtained without functional damage. The IABT was well tolerated. The visual and cosmetic results were satisfactory. Postoperative complications occurred in 7 out of 26 cases without a serious long-term adverse event. Significant radiation-induced complications were found in patients with orbital or skull base involvement. The three years overall survival was 60% for rhabdomyosarcoma, and 33% for the paranasal sinus cancers. CONCLUSIONS: These results show that a combined treatment of function-preserving surgery and a IABT is a feasible, successful and well-tolerated option for curative, salvage and palliative therapy for selected patients with advanced or recurrent carcinoma of the paranasal sinuses and orbit. PMID- 20352603 TI - Foramen magnum meningioma: successful surgical resection in a 76-year-old Nigerian. PMID- 20352604 TI - [Country-specific differences in the utilisation profiles of cross-border health care point to differentiated degrees of interest and selective use. Results of a German-Swiss pilot project]. AB - AIM: The pilot project Lorrach-Basel was implemented in 2007 to reduce the border effect in respect to the health care services for the citizens of the region. The study deals with the questions as to which patient groups utilise cross-border health care, with special regard to the accompanying financial streams, and what implications these utilisation profiles will have for the development of a health region. METHODS: Applications for cost assumption and hospital routine data concerning cross-border care, data of legal health insurance schemes of both participating countries for the financing of border crossers' medical care, in addition, question-related contents from expert interviews with hospitals or rehabilitation facilities in both countries and a random sample from routine hospital data of treatments in Switzerland under complementary private insurance terms were analysed. RESULTS: Regarding the actual use of the pilot project by Swiss insured persons in the second project year, an exclusive utilisation appeared in the area of rehabilitation with a total of 125 cases. 73% of all treatments took place in two rehabilitation centres. Only 8 cases from the German side corresponded to the framework of the pilot project and concerned - according to contract - highly specialised in-patient care. The applications for cost assumption addressed to German legal health insurance schemes aimed at a wide spectrum which went beyond the offer within the pilot project's framework. Only one-half of the top 10 locations by number of applications are a partner in the pilot project. When looking at the whole transnational patient mobility in the border region of Basel-Lorrach, including the cases financed by complementary insurances and schemes for border crossers, but with the exception of private insured persons, a nearly well-balanced mutual use of the medical offers (scale: by 4 million Euros) is found concerning the costs. Persons insured in Basel consume more medical care within the scope of the compulsory health insurance in Lorrach than persons, insured in Lorrach, consumed in Basel; the reverse trend appears for treatment cases financed by complementary insurances. CONCLUSIONS: The differences concerning age groups, contents and kinds of treatment point in the direction of a search for complementary potentials with the aim of adapting the cross-border health care offers to the future needs of the region. PMID- 20352605 TI - [Political implementation of prevention: the discussion about the ten principles of German concerted action in the health system]. AB - The "ten principles", developed by the Federal Ministry of Labour in 1985, mark an important turning point in the government's efforts to reform the health-care system. Citizens' self-reliance became a central objective. The implementation of the idea of prevention--postulated in the principles as well--was generally welcomed, but accentuated in different ways by the various stakeholders. An extension of specific measures, for example in occupational medicine, was rejected by liberal business circles. PMID- 20352606 TI - [Erich Wulff (1926-2010)]. PMID- 20352609 TI - [Formulation of a new reimbursement system for psychiatry/psychosomatic medicine]. PMID- 20352610 TI - [A new reimbursement system for psychiatry and psychosomatic medicine]. PMID- 20352611 TI - Selective hydrogenolysis of glycerol to propylene glycol on Cu-ZnO composite catalysts: structural requirements and reaction mechanism. AB - Cu-ZnO catalysts were prepared by homogeneous coprecipitation with varying Cu/Zn atomic ratios (0.4-2:1). The catalysts were examined in selective hydrogenolysis of glycerol to propylene glycol. Although propylene glycol selectivities remained essentially constant (over 93%) on the different Cu-ZnO catalysts, the turnover frequencies changed markedly with the Cu/Zn ratio, and reached the greatest value at the ratio of 1:1. Such activity dependence on the Cu/Zn ratio was in parallel with the change in the interaction between Cu and ZnO and in the Cu microstrain, as a consequence of the effects on the crystalline phases of hydroxycarbonate precursors for the Cu-ZnO catalysts, reflecting the structural requirements for glycerol hydrogenolysis. The hydrogenolysis mechanism was also examined and apparently involves kinetically relevant glycerol dehydrogenation to glyceraldehyde on Cu-ZnO and subsequent glyceraldehyde dehydration and hydrogenation to propylene glycol. The mechanism is consistent with the observed superior activities of the more strained Cu particles, and the higher propylene glycol selectivities obtained at higher glycerol and hydrogen concentrations. These findings provide a rationale for the design of more effective Cu-based catalysts in selective hydrogenolysis of glycerol and other biomass-derived polyols, for example, by synthesis of highly strained Cu particles strongly interacting with ZnO or other oxide supports. PMID- 20352612 TI - Determination of piracetam in rat plasma by LC-MS/MS and its application to pharmacokinetics. AB - A sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of piracetam in rat plasma was developed and validated over the concentration range of 0.1-20 ug/mL. After addition of oxiracetam as internal standard, a simplified protein precipitation with trichloroacetic acid (5%) was employed for the sample preparation. Chromatographic separation was performed by a Zorbax SB-Aq column (150 * 2.1 mm, 3.5 um). The mobile phase was acetonitrile 1% formic acid in water (10:90 v/v) delivered at a flow rate of 0.3 mL/min. The MS data acquisition was accomplished in multiple reaction monitoring mode with a positive electrospray ionization interface. The lower limit of quantification was 0.1 ug/mL. For inter-day and intra-day tests, the precision (RSD) for the entire validation was less than 9%, and the accuracy was within the 94.6-103.2% range. The developed method was successfully applied to pharmacokinetic studies of piracetam in rats following single oral administration dose of 50 mg/kg. PMID- 20352613 TI - Identification of ilaprazole metabolites in human urine by HPLC-ESI-MS/MS and HPLC-NMR experiments. AB - Ilaprazole is a new proton pump inhibitor designed for the treatment of gastric ulcers, and limited data is available on the metabolism of the drug. In this article, the structural elucidation of urinary metabolites of ilaprazole in human was described by HPLC-ESI-MS/MS and stopped-flow HPLC-NMR experiments. Urinary samples were precipitated by sodium carbonate solution, and then extracted by liquid-liquid extraction after adding ammonium acetate buffer solution. The enriched sample was separated using a C(18) reversed-phase column with the mobile phase composed of acetonitrile and 0.05 mol/L ammonium acetate buffer solution in a gradient solution, and then directly coupled to ESI-MS/MS detection in an on line mode or (1)H-NMR (500 MHz) spectroscopic detection in a stopped-flow mode. As a result, four sulfide metabolites, ilaprazole sulfide (M1), 12-hydroxy ilaprazole sulfide (M2), 11,12-dihydroxy-ilaprazole sulfide (M3) and ilaprazole sulfide A (M4), were identified by comparing their MS/MS and NMR data with those of the parent drug and available standard compounds. The main biotransformation reactions of ilaprazole were reduction and the aromatic hydroxylation of the parent drug and its relative metabolites. The result testified that HPLC-ESI MS/MS and HPLC-NMR could be widely applied in detection and identification of novel metabolites. PMID- 20352614 TI - Determination of sphingosine kinase activity in biological samples by liquid chromatography-tandem mass spectrometry. AB - Sphingosine kinase (SphK) is a key enzyme in modulating the levels of sphingosine 1-phosphate (S1P) as well as an important enzyme in numerous biological responses. Using C17-sphingosine as a substrate, we established a rapid, sensitive and highly efficient method for determination of SphK activity by analyzing the product C17-sphingosine 1-phosphate (C17-S1P) using liquid chromatography-tandem mass spectrometry. The standard curve for C17-S1P was linear over a wide range (10-1000 ng/mL) with correlation coefficient (r(2)) greater than 0.999. The lower limit of quantification for C17-S1P was 10 ng/mL. The K(m) values for C17-sphingosine and ATP were determined to be 28.17 and 188.5 microM, respectively. More importantly, the SphK activity dramatically increased in cultured HEK 293 cells expressing wild-type SphK1 as well as cells treated with tumor necrosis factor-alpha, a sphingosine kinase activator. In contrast, the SphK activity decreased in cultured HEK 293 cells treated with dimethylsphngosine, a sphingosine kinase inhibitor. In conclusion, this method was sensitive and rapid in the determination of SphK acitivity, providing striking utilities in exploring the sphingosine kinase signaling pathway and screening active compounds targeting SphK activity. PMID- 20352615 TI - A highly sensitive LC-MS/MS method for the determination of S-citalopram in rat plasma: application to a pharmacokinetic study in rats. AB - A highly sensitive, rapid assay method has been developed and validated for the estimation of S-citalopram (S-CPM) in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive ion mode. The assay procedure involves a simple liquid-liquid extraction of S-CPM and phenacetin (internal standard, IS) from rat plasma with t-butyl methyl ether. Chromatographic separation was operated with 0.2% formic acid:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Symmetry Shield RP(18) column with a total run time of 3.0 min. The MS/MS ion transitions monitored were 325.26 -> 109.10 for S-CPM and 180.10 -> 110.10 for IS. Method validation and pre clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.5 ng/mL and the linearity was observed from 0.5 to 5000 ng/mL. The intra- and inter-day precisions were in the range of 1.14-5.56 and 0.25-12.3%, respectively. This novel method has been applied to a pharmacokinetic study and to estimate brain-to plasma ratio of S-CPM in rats. PMID- 20352616 TI - Sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of metoclopramide in human plasma: application to a bioequivalence study. AB - A simple, sensitive and rapid method has been developed and validated for determination of the metoclopramide (MCP) in 100 microL human plasma. The analytical procedure involves a liquid-liquid extraction method using tramadol as an internal standard (IS). Chromatographic separation was carried out on a HyPURITY ADVANCE column using a mobile phase consisting of acetonitrile and 10 mm ammonium acetate buffer in the ratio of 80:20 (v/v) at a flow rate of 0.3 mL/min. The total run time of analysis was 2.5 min and elution of MCP and IS occurred at 0.9 and 1.3 min, respectively. A linear response function was established for the range of concentrations 0.53-42.07 ng/mL (r > 0.99). The intra- and inter-day precision values for MCP met the acceptance as per FDA guidelines. MCP was stable in a battery of stability studies viz., bench-top, auto-sampler and freeze-thaw cycles. The developed assay method was successfully applied to an oral bioequivalence study in humans. PMID- 20352617 TI - Biodistribution and safety assessment of AAV2-GAD following intrasubthalamic injection in the rat. AB - BACKGROUND: The steps necessary to translate promising new biological therapies to the clinic are poorly documented. For gene therapy, there are unique aspects that need to be addressed in biodistribution studies. Notably, the spread of the vector beyond the intended target cells or tissue may result in persistent unwanted biological activity or unpredictable biological events; thus, it is critical to evaluate the risks associated with viral vector-mediated gene transfer prior to embarking on human clinical trials. METHODS: In the present study, we conducted a comprehensive assessment of vector biodistribution throughout the brain, blood and major organs of rats that had been injected via the subthalamic nucleus with recombinant adeno-associated virus (AAV) expressing glutamic acid decarboxylase (GAD). In addition, behavioral and histological analyses were also performed. RESULTS: AAV genomes were not detected in blood or cerebrospinal fluid, and did not disseminate to organs outside of the brain in the majority of animals. In the brain, an average of 97.3% of AAV2-GAD genomes were restricted to the area of the ipsilateral subthalamic nucleus (STN). There were no discernable effects of AAV2-GAD on general health, and a behavioral assessment of the animals did not reveal any alteration in general behavior, exploration, locomotion or motor symmetry. CONCLUSIONS: The present study met Food and Drug Administration requirements, in addition to efficacy and toxicity studies in rodents and nonhuman primates, to support and supplement a Phase II clinical trial invloving the gene transfer of AAV2-GAD to the human STN for the potential therapy of Parkinson's disease. PMID- 20352618 TI - A Mediterranean diet rich in virgin olive oil may reverse the effects of the 174G/C IL6 gene variant on 3-year body weight change. AB - Only a few studies have analyzed the effects of the potential interaction between the -174G/C polymorphism of IL6 gene and the adherence to the Mediterranean diet (MD) on adiposity indexes. Our aim was to investigate the interplay between the 174G/C polymorphism of the IL6 gene and a Mediterranean-style diet on body weight changes after 3 years of nutritional intervention in a high cardiovascular risk population. A total of 737 participants, aged 55-80 years were assigned to a low fat diet or to a Mediterranean-style diet group with high intake of virgin olive oil (VOO) or nuts. Anthropometric measurements were taken at baseline and after 3 year follow-up. The -174G/C polymorphism of the IL6 gene was genotyped. Minor allele frequency (C) was 0.39. At baseline, the CC genotype was associated with higher measures of adiposity. After 3 years, a significant interaction (p=0.028) was found between the polymorphism (GG+GC versus CC) and the nutritional intervention: CC subjects following the MD+VOO had the lowest body weight gain. In conclusion, at baseline, CC subjects for the -174G/C polymorphism of IL6 had the highest body weight and BMI. However, after 3 years of nutritional intervention with MD+VOO, these subjects were predicted to have the greatest reduction in body weight. PMID- 20352619 TI - Acute and chronic effects of dietary fatty acids on cholecystokinin expression, storage and secretion in enteroendocrine STC-1 cells. AB - Cholecystokinin (CCK) is a peptide hormone secreted from the I-cells of the intestine and it has important physiological actions related to appetite regulation and satiety. In this study we used STC-1 cells to investigate the effects of common dietary-derived fatty acids (FAs) on I-cell secretory function and metabolism. We extend earlier studies by measuring the acute and chronic effects of 11 FAs on CCK secretion, cellular CCK content, CCK mRNA levels, cellular DNA synthesis, cellular viability and cytotoxicity. FAs were selected in order to assess the importance of chain length, degree of saturation, and double bond position and conformation. The results demonstrate that secretory responses elicited by dietary FAs are highly selective. For example, altering the conformation of a double bond from cis to trans (i.e. oleic acid versus elaidic acid) completely abolishes CCK secretion. Lauric acid appears to adversely affect I-cell metabolism and arachidonic acid suppresses DNA synthesis. Our studies reveal for the first time that conjugated linoleic acid isoforms are particularly potent CCK secretagogues, which also boost intracellular stores of CCK. These actions of conjugated linoleic acid may explain satiating actions observed in dietary intervention studies. PMID- 20352620 TI - Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes. AB - Recent studies have shown the ability of apelin to restore glucose tolerance in obese and insulin-resistant mice. Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) from the omega-3 family that has many beneficial effects in obesity-linked disorders. The aim of this study was to examine in vitro the effects of EPA on apelin secretion and gene expression in mature 3T3-L1 adipocytes. Treatment with EPA (100 and 200 microM) significantly increased basal (p<0.01) and insulin-stimulated (p<0.001) apelin secretion and gene expression in adipocytes. EPA also stimulated Akt phosphorylation, a down stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes. Moreover, treatment with the PI3K inhibitor LY294002 completely blocked EPA stimulatory action on apelin mRNA gene expression (p<0.001), but not modified the stimulatory effect of EPA on basal apelin secretion. Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms. These findings suggest that the mechanisms mediating EPA-induced apelin synthesis and/or secretion are complex, involving steps that are PI3K dependent and steps that are PI3K independent. PMID- 20352621 TI - Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. AB - Metastasis is one of the most important factors related to breast cancer therapeutic efficacy. Ursolic acid, a naturally occurring triterpenoid, has various anticancer activities. In this study, we first observed that ursolic acid exerted a dose- and time-dependent inhibitory effect on the migration and invasion of highly metastatic breast MDAMB231 cells at non-cytotoxic concentrations. This effect was associated with reduced activities of metalloproteinase-2 (MMP-2) and u-PA, which correlated with enhanced expression of tissue inhibitor of MMP-2 and plasminogen activator inhibitor-1, respectively. Ursolic acid suppressed the phosphorylation of Jun N-terminal kinase, Akt and mammalian target of rapamycin, but had no effect on the phosphorylation of ERK and p38. Ursolic acid also strongly reduced the levels of NFkappaB p65, c-Jun and c-Fos proteins in the nucleus of MDAMB231 cells. A time-dependent inhibition of the protein levels of Rho-like GTPases, growth factor receptor-bound protein 2, Ras and vascular endothelial growth factor in cytosol by ursolic acid treatment was also observed. In conclusion, we demonstrated that the anti-invasive effects of ursolic acid on MDAMB231 cells might be through the inhibition of Jun N terminal kinase, Akt and mammalian target of rapamycin phosphorylation and a reduction of the level of NFkappaB protein in the nucleus, ultimately leading to downregulation of MMP-2 and u-PA expression. These results suggest that ursolic acid has potential as a chemopreventive agent for metastatic breast cancer. PMID- 20352622 TI - An estimate of the economic burden and premature deaths due to vitamin D deficiency in Canada. AB - The objective of this work is to estimate the economic burden and premature death rate in Canada attributable to low serum 25-hydroxyvitamin D (25(OH)D) levels. Vitamin D deficiency has been linked to many diseases and conditions in addition to bone diseases, including many types of cancer, several bacterial and viral infections, autoimmune diseases, cardiovascular diseases, and adverse pregnancy outcomes. Canadians have mean serum 25(OH)D levels averaging 67 nmol/L. The journal literature was searched for papers reporting dose-response relationships for vitamin D indices and disease outcomes. The types of studies useful in this regard include randomized controlled trials, observational, cross-sectional, and ecological studies, and meta-analyses. The mortality rates for 2005 were obtained from Statistics Canada. The economic burden data were obtained from Health Canada. The estimated benefits in disease reduction were based on increasing the mean serum 25(OH)D level to 105 nmol/L. It is estimated that the death rate could fall by 37,000 deaths (22,300-52,300 deaths), representing 16.1% (9.7-22.7%) of annuals deaths and the economic burden by 6.9% (3.8-10.0%) or $14.4 billion ($8.0 billion-$20.1 billion) less the cost of the program. It is recommended that Canadian health policy leaders consider measures to increase serum 25(OH)D levels for all Canadians. PMID- 20352623 TI - Vitamin D deficiency and myocardial diseases. AB - Vitamin D deficiency is common among patients with myocardial diseases because sun-induced vitamin D production in the skin and dietary intake of vitamin D is often insufficient. Knockout mice for the vitamin D receptor develop myocardial hypertrophy and dysfunction. It has also been shown that children with rickets who suffered from severe heart failure could be successfully treated with supplementation of vitamin D plus calcium. In adults, almost all patients with heart failure exhibit reduced 25-hydroxyvitamin D levels, which are used to classify the vitamin D status. In prospective studies, vitamin D deficiency was an independent risk factor for mortality, deaths due to heart failure and sudden cardiac death. Several vitamin D effects on the electrophysiology, contractility, and structure of the heart suggest that vitamin D deficiency might be a causal factor for myocardial diseases. Data from interventional trials, however, are rare and urgently needed to elucidate whether vitamin D supplementation is useful for the treatment of myocardial diseases. In our opinion, the current knowledge of the beneficial effects of vitamin D on myocardial and overall health strongly argue for vitamin D supplementation in all vitamin D-deficient patients with or at high risk for myocardial diseases. PMID- 20352625 TI - Balancing robust quantification and identification for iTRAQ: application of UHR ToF MS. AB - iTRAQ reagents allow the simultaneous multiplex identification and quantification of a large number of proteins. Success depends on effective peptide fragmentation in order to generate both peptide sequence ions (higher mass region, 150-2200 m/z) and reporter ions (low mass region, 113-121 m/z) for protein identification and relative quantification, respectively. After collision-induced dissociation, the key requirements to achieve a good balance between the high and low m/z ions are effective ion transmission and detection across the MS/MS mass range, since the ion transmission of the higher m/z range competes with that of the low m/z range. This study describes an analytical strategy for the implementation of iTRAQ on maXis UHR-Qq-ToF instruments, and discusses the impact of adjusting the MS/MS ion transmission parameters on the quality of the overall data sets. A technical discussion highlights a number of maXis-specific parameters, their impact of quantification and identification, and their cross-interactions. PMID- 20352624 TI - Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia. AB - Human autoimmune diseases are often characterized by a relative deficiency in CD4(+)CD25(+) regulatory T cells (Treg). We therefore hypothesized that expansion of Treg can ameliorate autoimmune pathology. We tested this hypothesis in an experimental model for autoimmune myasthenia gravis (MG), a B-cell-mediated disease characterized by auto-Ab directed against the acetylcholine receptor within neuromuscular junctions. We showed that injection of immune complexes composed of the cytokine IL-2 and anti-IL-2 mAb (JES6-1A12) induced an effective and sustained expansion of Treg, via peripheral proliferation of CD4(+)CD25(+)Foxp3(+) cells and peripheral conversion of CD4(+)CD25(-)Foxp3(-) cells. The expanded Treg potently suppressed autoreactive T- and B-cell responses to acetylcholine receptor and attenuated the muscular weakness that is characteristic of MG. Thus, IL-2/anti-IL-2 mAb complexes can expand functional Treg in vivo, providing a potential clinical application of this modality for treatment of MG and other autoimmune disorders. PMID- 20352626 TI - Quantitative milk proteomics--host responses to lipopolysaccharide-mediated inflammation of bovine mammary gland. AB - Intramammary infusion of lipopolysaccharide (LPS) in cows induces udder inflammation that partly simulates mastitis caused by infection with Gram negative bacteria. We have used this animal model to characterize the quantitiative response in the milk proteome during the time course before and immediately after the LPS challenge. Milk samples from three healthy cows collected 3 h before the LPS challenge were compared with milk samples collected 4 and 7 h after the LPS challenge, making it possible to describe the inflammatory response of individual cows. Quantitative protein profiles were obtained for 80 milk proteins, of which 49 profiles changed significantly for the three cows during LPS challenge. New information obtained in this study includes the quantified increase of apolipoproteins and other anti-inflammatory proteins in milk, which are important for the cow's ability to balance the immune response, and the upregulation of both complement C3 and C4 indicates that more than one complement pathway could be activated during LPS-induced mastitis. In the future, this analytical approach may provide valuable information about the differences in the ability of individual cows to resist and recover from mastitis. PMID- 20352627 TI - Chemical modification of hydrophobic block in poly(ethylene oxide) poly(caprolactone) based nanocarriers: effect on the solubilization and hemolytic activity of amphotericin B. AB - The aim of this study was to develop methoxy poly(ethylene oxide)-b-poly(epsilon caprolactone) (MePEO-b-PCL) containing stearyl (St) substituents on PCL, and assess the efficacy of nanocarriers formed from this structure in comparison to unmodified MePEO-b-PCL and those with carboxyl substitutes on PCL on the solubilization and delivery of Amphotericin B (AmB). Prepared block copolymers were characterized for their molecular weight by (1)H NMR and gel permeation chromatography. The self-assembly of synthesized MePEO-b-PStCL to spherical particles of nanometer size range was shown by dynamic light scattering as well as electron and atomic force microscopy. Encapsulated AmB showed a reduction in its hemolytic activity against rat red blood cells in comparison to the commercial formulation of AmB, Fungizone. PMID- 20352628 TI - 1-nanometer-sized active-channel molecular quantum-dot transistor. PMID- 20352629 TI - Peptide/graphene hybrid assembly into core/shell nanowires. PMID- 20352630 TI - Organic infrared upconversion device. PMID- 20352631 TI - Freestanding graphene by thermal splitting of silicon carbide granules. PMID- 20352632 TI - High mobility ambipolar charge transport in polyselenophene conjugated polymers. PMID- 20352633 TI - Electric-field enhancement of photovoltaic devices: a third reason for the increase in the efficiency of photovoltaic devices by carbon nanotubes. PMID- 20352634 TI - Advanced optical metamaterials. PMID- 20352635 TI - Evidence for a broad transition-state ensemble in calmodulin folding from single molecule force spectroscopy. PMID- 20352636 TI - Rh(I)-catalyzed cycloisomerization of vinyl bicyclopropyl compounds to azabicyclo[3.2.2]nona-2,8-dienes. PMID- 20352637 TI - The effect of incorporating Frechet dendrons into rotaxanes and molecular shuttles containing the 1,2-bis(pyridinium)ethane?[24]crown-8 templating motif. AB - Frechet-type dendrons (G0-G3) were added as both axle stoppering units and cyclic wheel appendages in a series of [2]rotaxanes, [3]rotaxanes, and molecular shuttles that employ 1,2-bis(pyridinium)ethane axles and 24-membered crown ethers wheels. The addition of dendrimer wedges as stoppering units dramatically increased the solubility of simple [2]rotaxanes in nonpolar solvents. The X-ray structure of a G1-stoppered [2]rotaxane shows how the dendritic units affect the structure of the interlocked components. Increased solubility allows observation of how the interaction of dendritic units on separate components in interlocked molecules influences switching properties and molecular size. In a series of [2]rotaxane molecular shuttles incorporating two recognition sites, it was demonstrated that an increase in generation on either the stoppering unit or cyclic wheel could influence both the rate of shuttling and the site preference of the wheel on the axle. PMID- 20352638 TI - Subsurface-controlled CO2 selectivity of PdZn near-surface alloys in H2 generation by methanol steam reforming. PMID- 20352639 TI - Probing the molecular recognition of a DNA.RNA hybrid duplex. PMID- 20352640 TI - Polycatenation under thermodynamic control. PMID- 20352641 TI - Diisopropylamide and TMP turbo-Grignard reagents: a structural rationale for their contrasting reactivities. PMID- 20352642 TI - Recent progress in the crystallographic studies of photosystem II. AB - The photosynthetic oxygen-evolving photosystem II (PSII) is the only known biochemical system that is able to oxidize water molecules and thereby generates almost all oxygen in the Earth's atmosphere. The elucidation of the structural and mechanistic aspects of PSII keeps scientists all over the world engaged since several decades. In this Minireview, we outline the progress in understanding PSII based on the most recent crystal structure at 2.9 A resolution. A likely position of the chloride ion, which is known to be required for the fast turnover of water oxidation, could be determined in native PSII and is compared with work on bromide and iodide substituted PSII. Moreover, eleven new integral lipids could be assigned, emphasizing the importance of lipids for the perfect function of PSII. A third plastoquinone molecule (Q(C)) and a second quinone transfer channel are revealed, making it possible to consider different mechanisms for the exchange of plastoquinone/plastoquinol molecules. In addition, possible transport channels for water, dioxygen and protons are identified. PMID- 20352643 TI - Solution-processed organic photovoltaic cells with anthracene derivatives. AB - Solution-processed small-molecule bulk heterojunction photovoltaic cells are fabricated by using [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) as electron acceptor and triisopropylsilylethynyl anthracene (TIPSAnt) derivatives substituted with naphthalene (TIPSAntNa) and bithiophene (TIPSAntBT) as electron donors. In contrast to TIPS-pentacene, the TIPSAnt derivatives are not susceptible to Diels-Alder reactions with PCBM when processed in solution, as confirmed by UV/Vis measurements. Photoluminescence quenching measurements show exciton diffusion lengths of 5 and 3 nm for TIPSAntBT and TIPSAntNa, respectively. Blending TIPSAntBT and TIPSAntNa with PCBM (1:1, 1:2, 1:3, and 1:4 weight ratios) produces films that possess adequate hole and electron mobilities. The morphological changes that result from varying the blending ratio range from obvious phase-segregated crystalline domains at a 1:1 ratio to homogeneous, nearly amorphous phases at a 1:4 ratio. Bulk heterojunction solar cells prepared by using a TIPSAntBT:PCBM blend reach power conversion efficiencies as high as 1.4 %. PMID- 20352644 TI - Near-infrared organic compounds and emerging applications. AB - This Focus Review describes the emerging class of near-infrared (NIR) organic compounds containing the conjugated polyene, polymethine, and donor-acceptor chromophores and exploration of their NIR-absorbing, NIR-fluorescence, and NIR photosensitizing properties for potential applications in heat absorbers, solar cells, and NIR light-emitting diodes. Examples of NIR organic compounds are reviewed with emphasis on the molecular design, NIR absorption, and fluorescence and particular emerging applications. The donor-acceptor type of NIR chromophores are particularly introduced owing to some unique features, including the designer made energy gaps, facile synthesis, good processability, and controllable morphology and properties in the solid state. Future directions in research and development of NIR organic materials and applications are then offered from a personal perspective. PMID- 20352645 TI - Treatment readiness, treatment engagement and behaviour change. AB - BACKGROUND: Non-completion of treatment is a common occurrence in correctional contexts. Non-completion compromises service cost-efficiency, impacts adversely on staff and service user morale and may limit the effectiveness of therapy. Attention needs to be paid to enhancing offenders' readiness for treatment, and developing and maintaining their engagement. ARGUMENT: In this paper, we state that research and practice in offender treatment readiness and engagement need to be driven in four major ways: (1) the construction of models of engagement that are theoretically based and empirically evidenced that can underpin assessments and treatments; (2) the development of psychometrically robust assessments of treatment readiness, motivation and engagement that can be used to select offenders for treatment or measure change over time; (3) the design, implementation and evaluation of pre-treatment preparation procedures that can promote treatment engagement and completion; and (4) the development of strategies that address barriers to engagement as an integral part of treatment. CONCLUSIONS: This special issue contains contributions from leading researchers on the assessment of engagement, effects of engagement and non-engagement on outcomes, offenders' reasons for non-completion of treatment programmes, and the development of a measure of offenders' current concerns and life aspirations. These studies will improve research and practice in offender treatment readiness and engagement, and this could lead to better outcomes in terms of reduced re offending. PMID- 20352646 TI - Treatment engagement as a predictor of premature treatment termination and treatment outcome in a correctional outpatient sample. AB - BACKGROUND: It is widely assumed that the outcome of correctional treatment largely depends on the patient's treatment engagement; however, evidence for this notion is scarce. AIM: In this study, the Treatment Engagement Rating scale (TER) was used to investigate the relationship of a patient's treatment engagement with premature treatment termination and treatment outcome, defined as reduction of the risk of reoffending. METHOD: Employing a prospective design, this study addressed the relationship of the behavioural treatment engagement of correctional outpatients (N = 138) with treatment non-completion and treatment outcome, respectively. RESULTS: Treatment engagement as measured by the TER emerged as an accurate predictor of treatment non-completion (area under the curve = 0.76; odds ratio = 4.1) and was also significantly correlated with treatment outcome (rho = 0.41). The prediction was more accurate for sex offenders than for violent offenders, for expulsion from the treatment than for dropout, and when treatment engagement was assessed closer to the end of the treatment. CONCLUSIONS: The study provides evidence that the outcome of correctional treatment depends to a substantial degree on the behavioural efforts that the patients make for the treatment. Periodic assessment of treatment engagement in correctional treatment facilities would be useful, and the TER seems to be a practical, reliable and valid instrument for this purpose. PMID- 20352647 TI - Do early therapeutic alliance, motivation, and stages of change predict therapy change for high-risk, psychopathic violent prisoners? AB - BACKGROUND: Examination of the extent of offenders' engagement in change, and in rehabilitation programmes, is important to understanding success or failure following rehabilitation. In treatment programmes, the alliance between therapist and offender, and the therapy process itself appear central to progress offenders make that may reduce their criminal risk. But research with offenders seldom has measured therapeutic alliance and clinical writing suggests that it is difficult to form an alliance with those not ready to change their behaviour; especially with higher risk and psychopathic offenders. AIMS AND METHODS: This study outlines the course of the therapeutic alliance in an 8-month treatment programme for high-risk, PCL-psychopathic violent prisoners. It examines relationships between early-treatment therapeutic alliance, therapists' global ratings of motivation to change, and initial stage of change on dynamic risk factors. In addition, it investigates which factors best predict who will complete treatment and change behaviourally during treatment. CONCLUSION: In this challenging, high needs client group, early-programme stage of change, therapists' perceptions of motivation, therapeutic alliance and psychopathy did not predict how much change prisoners made. Regardless of initial levels, prisoners whose alliance increased the most over the course of treatment made the most change. PMID- 20352648 TI - Engagement in a medium secure personality disorder service: a comparative study of psychological functioning and offending outcomes. AB - BACKGROUND: Specialist treatment programmes for personality disordered offenders suffer from high rates of non-completion. This has important consequences for service providers and individual patients. METHOD: Data from hospital records and the Offenders Index were compared for groups of treatment completers (n = 22) and non-completers (n = 59) discharged from a specialist treatment programme. RESULTS: Twenty-seven percent of patients completed treatment, 37% were expelled for rule breaking and 35% disengaged early from treatment. Psychometric assessments of anger expression and anxiety showed no differences between the groups, however, treatment completers showed lower levels of impulsivity and psychopathy than either of the non-completer groups. Rates of post-discharge offending for grave and standard list offences were 56.8 and 10.8%, respectively. CONCLUSIONS: Despite careful selection methods, a large proportion of personality disordered patients admitted to specialist units failed to complete treatment. Psychometric assessments of anger expression, anxiety and impulsivity showed limited utility in differentiating treatment completers and non-completers. Sample size limitations in this naturalistic follow-up impacted on the interpretation of differences observed between the groups on the primary outcome measure of re-offending after discharge. PMID- 20352649 TI - An empirical evaluation of reasons for non-completion of treatment in a dangerous and severe personality disorder unit. AB - BACKGROUND: Individuals deemed to be of high risk to others, and diagnosed with severe personality disorders have become the focus for developing clinical services in England. Such services often require highly secure accommodation and labour-intensive therapeutic interventions. There is, however, uncertainty about the capacity to engage such patients effectively in therapies. AIM: Here, we examine service evaluation monitoring data to identify the level of completion of therapeutic programmes in a high secure severe personality disordered population, and analyse reasons for failure to complete. METHOD: Guidelines for classifying reasons for non-completion were developed, based on the multifactorial offender readiness model (MORM). Electronic case notes were searched for references to non completion, and recorded reasons for non-completion were classified. RESULTS: Non completion was at a relatively modest level. The main reasons for non-completion were: (1) affective: general distress of the patient or specific emotional reactions to previous offending, e.g. shame; (2) volitional: pursuing goals other than treatment; and (3) cognitive: negative self-efficacy beliefs and negative evaluations (low trust) of staff and the programme. External factors included exclusion from treatment and transfer to another unit. CONCLUSION: This study identifies specific readiness areas that might need to be addressed in efforts to improve engagement and retention in treatment. A wider range of methodologies is required for future studies. PMID- 20352650 TI - Personal aspirations and concerns inventory for offenders: developments in the measurement of offenders' motivation. AB - BACKGROUND: It is important to attend to offenders' motivation for treatment and behaviour change, either as a treatment selection criterion or a pre-treatment need. One measure of motivation that has been used with forensic populations is the Personal Concerns Inventory (PCI) and a PCI-Offender Adaptation (PCI-OA). As well as demonstrating promise in measuring offenders' motivation, the administration of the PCI and PCI-OA shows potential as a motivation enhancer. However, a number of potentially useful changes to the PCI-OA that may maximise its potential have been identified. These are described here. METHOD: The rationale and process of abridgement and further development of the PCI-OA into the Personal Aspirations and Concerns Inventory for Offenders (PACI-O) are described. Results of a pilot study with 22 prisoners are reported. The pilot study aimed to assess the acceptability of the PACI-O with an offender population. RESULTS: Findings demonstrated that the interview took less time, although similar concerns were still identified, consistent with the previous PCI OA. CONCLUSION: Consistency with previous evidence, together with positive feedback, suggests that the PACI-O was acceptable with an offender population. Future research is required to assess the psychometric properties of the PACI-O, and to evaluate its potential as an assessment of offender motivation. PMID- 20352651 TI - Applications of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) in pharmaceutical and biological analysis. AB - Conductivity detection, which is universal in capillary electrophoresis (CE), has received considerable attention, since the introduction of the axial capacitively coupled contactless detector C(4)D in 1998. This detector is made of two electrodes which are placed cylindrically around the CE capillary and connected to the AC oscillator. The distance between the electrodes is the detection gap. In this review, applications of CE and MCE with C(4)D in pharmaceutical and biological analysis are presented. PMID- 20352652 TI - Simultaneous determination of phthalates and adipates in human serum using gas chromatography-mass spectrometry with solid-phase extraction. AB - A gas chromatography-mass spectrometry assay was developed and validated for the simultaneous determination of phthalates and adipates in human serum. The phthalates and adipates studied were dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate, di-n-octyl phthalate, diethyl adipate, dibutyl adipate, diisobutyl adipate, bis(2 butoxyethyl) adipate and di-2-ethylhexyl adipate, with diisooctyl phthalate as internal standard. The extraction and cleaning up procedure was carried out with solid-phase extraction cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 88% for each analyte and the internal standard. The calibration curves obtained were linear with correlation coefficients greater than 0.98. For all analytes, the assay gave CV% values for intra-day precision from 4.9 to 13.3% and mean accuracy values from 91.4 to 108.4%, while inter-day precision was 5.2-13.4% and mean accuracy 91.0-110.2%. The limits of detection for the assay of phthalates and adipates were in the range 0.7-4.5 ng/mL. The method is simple, sensitive and accurate, and allows for simultaneous determination of nanogram levels of phthalates and adipates in human serum. It was successfully applied to an investigation on the level of phthalates and adipates in a non-occupationally exposed population. PMID- 20352653 TI - Innovative photonic micromanipulation tools: light takes hold in Biophotonics. PMID- 20352657 TI - Rainy season could hamper Haiti's recovery. PMID- 20352658 TI - Romania mulls over fast food tax. PMID- 20352659 TI - Remaking the moral person in China: implications for health. PMID- 20352660 TI - Transcription attenuation in bacteria: theme and variations. AB - Premature termination of transcription, or attenuation, is an efficient RNA-based regulatory strategy that is commonly used in bacterial organisms. Attenuators are generally located in the 50 untranslated regions of genes or operons and combine a Rho-independent terminator, controlling transcription, with an RNA element that senses specific environmental signals. A striking diversity of sensing elements enable regulation of gene expression in response to multiple environmental conditions, including temperature changes, availability of small metabolites(such as ions, amino acids, nucleobases or vitamins), or availability of macromolecules such as tRNAs and regulatory proteins. The wide distribution of attenuators suggests an early emergence among bacteria. However, attenuators also display a great mobility and lability, illustrated by a multiplicity of recent horizontal transfers and duplications.For these reasons, attenuation systems are of high interest both from a fundamental evolutionary perspective and for possible biotechnological applications. PMID- 20352661 TI - [Positive for HIV positive mothers]. PMID- 20352662 TI - National Practitioner Data Bank for Adverse Information on Physicians and Other Health Care Practitioners: reporting on adverse and negative actions. Final rule. AB - This final rule revises existing regulations under sections 401 through 432 of the Health Care Quality Improvement Act of 1986, governing the National Practitioner Data Bank for Adverse Information on Physicians and Other Health Care Practitioners, to incorporate statutory requirements under section 1921 of the Social Security Act, as amended by section 5(b) of the Medicare and Medicaid Patient and Program Protection Act of 1987 (MMPPPA), and as amended by the Omnibus Budget Reconciliation Act of 1990 (OBRA). The MMPPPA, along with certain additional provisions in the OBRA, was designed to protect program beneficiaries from unfit health care practitioners, and otherwise improve the anti-fraud provisions of Medicare and State health care programs. Section 1921, the statutory authority upon which this regulatory action is based, requires each State to adopt a system of reporting to the Secretary of Health and Human Services (the Secretary) certain adverse licensure actions taken against health care practitioners and health care entities licensed or otherwise authorized by a State (or a political subdivision thereof) to provide health care services. It also requires each State to report any negative actions or findings that a State licensing authority, peer review organization, or private accreditation entity has concluded against a health care practitioner or health care entity. PMID- 20352663 TI - Registration requirements for importers and manufacturers of prescription drug products containing ephedrine, pseudoephedrine, or phenylpropanolamine. Final rule. AB - The Drug Enforcement Administration (DEA) is amending its registration regulations to ensure that a registration is obtained for every location where ephedrine, pseudoephedrine, or phenylpropanolamine, or drug products containing one of these chemicals, are imported or manufactured. These amendments will make it possible to establish the system of quotas and assessment of annual needs for the importation and manufacture of these chemicals that Congress mandated in the Combat Methamphetamine Epidemic Act of 2005. PMID- 20352664 TI - Javier Garau: eyeing the horizons of infectious disease. Interview by Peter Hayward. PMID- 20352665 TI - Interim final rules under the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008. Interim final rules with request for comments. AB - This document contains interim final rules implementing the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008, which requires parity between mental health or substance use disorder benefits and medical/surgical benefits with respect to financial requirements and treatment limitations under group health plans and health insurance coverage offered in connection with a group health plan. PMID- 20352666 TI - Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis. AB - In recent years, a number of gene clusters involved in the biosynthesis of polyketide compounds have been characterized and the genes have been used for designing and developing novel chemical entities by combinatorial biosynthesis. This review covers the highlights of combinatorial biosynthesis using polyketide modifying enzymes such as oxidoreductases, group transferases, halogenases, cyclases and deoxysugar biosynthesis enzymes, focusing on those from actinomycetes (with 315 references cited). PMID- 20352667 TI - [Osteochondroma of the scapula manifesting as a cyst mass]. PMID- 20352668 TI - [Insulinoma: the state of art]. PMID- 20352669 TI - [Osteomielitis of sternoclavicular junction]. PMID- 20352670 TI - Report of the poison control centre for the period 1 January - 31 December 2009. PMID- 20352671 TI - Hydration of nucleic acid bases: a Car-Parrinello molecular dynamics approach. AB - Comprehensive study on interactions between nucleic acid bases (NABs) and bulk water environment has been performed with use of Car-Parrinello molecular dynamics. Detailed analysis of average number, lifetimes and mobility of water molecules, orientation and 3D organization of hydrogen bond network in the first hydration shell of adenine, guanine, cytosine and thymine has been carried out. Effect of hydration by bulk water environment has been compared with the data from polyhydrated complexes of NABs. During bulk water hydration the presence of mixed Hw...N/Hw...pi type of bonding is detected for imino nitrogen atoms. The formation of three hydrogen bonds to carbonyl groups reflects the significance of polarizing effects of aqueous environments. Hydration of hydrophobic sites revealed the presence of extremely weak bonding. Hydration of C6-H6 site of thymine is standing significantly apart from the hydration of other hydrophobic sites. An average coordination numbers of adenine, guanine, cytosine and thymine in bulk water environment are 6.87, 8.52, 6.12 and 6.42 water molecules, correspondingly. The lifetime of water molecules in the first hydration shell varies from 1 to 3 ps. Some differences in hydration studied by CPMD (bulk water) and quantum chemical (less than 20 water molecules) methods indicate a significant effect of the second hydration shell on structure and properties of the first hydration shell for the considered compounds. PMID- 20352672 TI - Peptide fragmentation by keV ion-induced dissociation. AB - We have studied multiple ionization and dissociation of a trapped protonated peptide (leucine enkephalin) as induced by keV singly and doubly charged ions (H(+), He(+, 2+)) to demonstrate the potential of keV ions as a future tool for peptide identification. In contrast to conventional excitation techniques, the fragmentation pattern exhibits very strong peaks due to loss of sidechains in addition to those due to backbone scission. The results can be understood on the basis of the energy deposited into the peptide via electronic stopping. A pronounced dependence of the fragmentation pattern on the electronic structure of the projectile ions can be attributed to different electron capture efficiencies from localized molecular orbitals. PMID- 20352673 TI - [Transcultural psychiatry. Bibliography]. PMID- 20352674 TI - [The Fifth Romanian Congress of the Society of Endoscopic Surgery and other Interventional Techniques. The Second Romanian Conference of Surgical Nurses. Symposium of the Romanian society of Pediatric Surgery, Minimally Invasive Techniques. Bucharest, November 11-14, 2009]. PMID- 20352675 TI - Infrared multiple photon dissociation spectroscopy of cationized methionine: effects of alkali-metal cation size on gas-phase conformation. AB - The gas-phase structures of alkali-metal cation complexes of the amino acid methionine (Met) as well as protonated methionine are investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser. Spectra of Li(+)(Met) and Na(+)(Met) are similar and relatively simple, whereas the spectra of K(+)(Met), Rb(+)(Met), and Cs(+)(Met) include distinctive new bands. Measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory to identify the conformations present in the experimental studies. For Li(+) and Na(+) complexes, the only conformation present is a charge-solvated, tridentate structure that binds the metal cation to the amine and carbonyl groups of the amino acid backbone and the sulfur atom of the side chain, [N,CO,S]. In addition to the [N,CO,S] conformer, bands corresponding to alkali-metal cation binding to a bidentate zwitterionic structure, [CO(2)(-)], are clearly present for the K(+), Rb(+), and Cs(+) complexes. Theoretical calculations of the lowest energy conformations of Rb(+) and Cs(+) complexes suggest that the experimental spectra could also include contributions from two additional charge-solvated structures, tridentate [COOH,S] and bidentate [COOH]. For H(+)(Met), the IRMPD action spectrum is reproduced by multiple low-energy [N,CO,S] conformers, in which the protonated amine group hydrogen bonds to the carbonyl oxygen atom and the sulfur atom of the amino acid side chain. These [N,CO,S] conformers only differ in their side-chain orientations. PMID- 20352676 TI - [1/6. Hospital administration, confidentiality, determination of the address and district]. PMID- 20352677 TI - Photodetachment of tryptophan anion: an optical probe of remote electron. AB - The UV photoexcitation spectrum of deprotonated tryptophan anion is presented. Singly deprotonated amino-acid tryptophan has been produced in an electrospray ionization source, isolated in a quadrupole ion trap and photoexcited with a UV tunable laser, resulting in the photodetachment of the excess electron. Whereas no influence of the proton on the UV spectrum of tryptophan was previously reported (Phys. Chem. Chem. Phys., 2004, 6, 2633; J. Chem. Phys., 2005, 122, 074310), we observe a strong bathochromism due to the presence of the negatively charged group in the vicinity of the chromophore. An excellent agreement with TD DFT (time dependent density functional theory) predictions for the absorption spectrum of the lowest energy conformer is found. The sensitivity of the tryptophan chromophore to the presence of a remote negative charge offers new perspectives for charge mapping in large biomolecules. PMID- 20352678 TI - Conformations and vibrational spectra of a model tripeptide: change of secondary structure upon micro-solvation. AB - Mid-infrared (IR) hole burning spectra of the model tripeptide Z-Aib-Pro-NHMe (Z = benzyloxycarbonyl) in gas phase and its micro-clusters with one and two methanol molecules are presented. To establish a relation between experimental spectra and the underlying conformations, calculations at the DFT [B3LYP/6 311++G(d,p)] level of theory are performed. In particular, the intra-peptide and the peptide-methanol hydrogen bonds can be identified from spectral shifts in the amide I, II, and III regions. While the unsolvated tripeptide as well as its one methanol cluster prefer a gamma-turn structure, a beta-turn structure is found for the two-methanol cluster, in agreement with previous condensed phase studies. Comparison of measured and simulated spectra reveals that the favorable methanol binding sites are at the head and tail parts of the tripeptide. The interconversions between gamma-turn and beta-turn structures are governed by potential barriers below 10 kJ mol(-1) inside one of the low energy basins of the potential energy surface. PMID- 20352679 TI - [EEG spatial synchronization at different set stages in 8-year-old children with different levels of selective attention fronto-thalamic system maturity]. AB - Visual cognitive set was studied in two groups of 8-year-old children: with normal development of fronto-thalamic system (FTS) (n = 21) and with functional immaturity of this system (n = 29). In most of the children with the FTS immaturity a formed visual set was rigid. EEG was recorded from the frontal, central, temporal, parietal and occipital regions, and coherence function in theta-, alpha- and beta-bands was analyzed. The most vivid differences between two groups of children were revealed at the set actualization stage. If the set was a plastic one, the value of coherence function between frontal and dorsal areas was higher in children with FTS-immaturity, than in "normal" ones. In the group with FTS-immaturity the dependence of coherence function on the set's plasticity was more vivid, than in children without FTS-immaturity. In all children with a rigid set value of coherence function was higher during set formation, actualization and extinction, than at resting condition with eyes opened. In the group with FTS-immaturity the coherence of theta-band considerably increased at the set actualization stage, mainly in the right hemisphere. We consider this to be the evidence of a comparatively bigger role of cortico hippocampal system and implicit episodic memory the set shifting. Probably these processes compensate the FTS-dysfunction and make a set more plastic. PMID- 20352680 TI - [Initiation potential of the brain cortex before memory-guided saccades]. AB - Longer latency and duration of memory-guided saccades and their lower amplitude compared with visually-guided saccades testify to the slower programming of the former. Lateral distinctions in the latencies and durations of memory-guided and visually-guided saccades can reflect leading role of the right hemisphere in programming memory-guided saccades and leading role of the left hemisphere in programming visually-guided saccades. Topography and spatiotemporal dynamics of presaccadic potentials P-1 and N-1 within the last 100 ms of latent period suggest that the mechanisms of final stage of the programming of memory-guided and visually-guided saccades are different. Shorter latencies of the presaccadic P-1 and N-1 prior to memory-guided saccades testify to acceleration of the initiation of the memory-guided saccades. The acceleration of the initiation period of memory-guided saccades suggest that deceleration of memory-guided saccade programming occurs at the stages preceding saccade initiation. PMID- 20352681 TI - [Verbal stimuli semantics and relevance of ERPs]. AB - In 22 healthy participants EEG from 28 channels was recorded during visual presentation of a random sequence of words and pseudo-words. The experiment consisted of three parts. In the first part the subjects just passively read the stimuli, in the second part they had to click the mouse button when seeing a word and in the third part--when seeing a pseudo-word. The results show that words are more significant to subjects than pseudo-words causing higher amplitude of P100 and P300 in the first and the second parts of the experiment, evidently, due to presence of meaning. However, the lexical task may be a more significant factor of the information processing than the presence of meaning, since in the third part of the experiment, where pseudo-words were relevant, they elicited higher amplitude of P300 than words. Pseudo-words elicited also negative N400 amplitude than words, revealing incongruity effect. However, when words were task incongruent, this effect is significantly less evident. PMID- 20352682 TI - [Responses of rabbit's visual cortex neurons to changes in intensity and orientation of visual stimuli]. AB - Changes in the number of spikes in the early phasic discharge (50-90 ms from stimuli replacement) of neurons in the rabbit's primary visual cortex were studied under conditions of an instant change in a flashing-line pattern. We used three type of stimulation: lines with different orientations (0-90 degrees) but constant intensity; lines with constant orientation but different intensities; complex stimuli with different intensities and different orientations of lines. Factor analysis made it possible to reconstruct two-dimensional sensory spaces of orientations in 13 of 43 analyzed neurons (30%). In 5 of 30 analyzed neurons (16.6%), both two-dimensional spaces of orientations and two-dimensional spaces of intensities were revealed. Achromatic spaces were reconstructed during changes in the lines of varying intensities but constant orientation. In experiments with complex stimuli, the intensity of lines with orientations varying from 0 to 38.58 degree was 5 cd/m2. The intensity of lines with orientations varying from 51.44 to 90 degrees was 15 cd/m2. In the sensorial space, stimuli with different intensities were located on the plane formed by the first and second significant factors in opposite quadrants, whereas within each quadrant, the stimuli were arranged closely to their orientation from minimum to maximum. We suggest that this type of sensory space reflects the interaction between intensity and orientation attributes of visual stimuli with the factor of intensity prevailing over the factor of orientation. Only 7 (12%) neurons with such complex spaces were found. PMID- 20352683 TI - [Interaction of stationary excitation foci in the rabbit brain]. AB - Influence of "animal hypnosis" on the motor polarization dominanta created by direct anodic current applied on the left sensorimotor cortex of the rabbit ("left" dominanta) was studied in chronic experiments. Animal behavior and electrophysiological characteristics were recorded. It was impossible to elicit the "animal hypnosis" during the optimum of the "left" dominanta. The state of "animal hypnosis" could be easily elicited against the background of the latent focus of the "left" dominanta on the next day after its formation. The "animal hypnosis" restored the "left" dominanta after its extinction. It was accompanied by formation of a new pattern of the cortical EEG coherence in the delta range, which was different from the patterns characteristic of each kind of dominanta. After the "animal hypnosis" session, the formation of the "left" dominanta produced two kinds of nonstable foci. During testing, the "left" dominanta reached its optimum and then inhibited the tonic activity of the right forelimb characteristic of the "animal hypnosis". The interaction of the "animal hypnosis" and the dominant foci in the left and right sensorimotor cortex were different. PMID- 20352684 TI - [Study of impulsivity in rats under conditions of choice between food reinforcements of different values]. AB - Rat behavior was studied under conditions "with the right to choose the values of reinforcements depending on the time delay of its receipt". Rats were placed in a chamber equipped with two retractable pedals, pressing one of which provided a small portion of food (1 pellet), and pressing the second pedal was followed by the delivery of more valuable food (4 pellets), but delayed reinforcement. Rats preferring small reinforcement without the delay were considered as "impulsive" and rats choosing more valuable delayed reinforcement were considered as "self controlling". Influence of the delay duration and change in the level of motivation on the pedal pressing was studied in both groups of rats. Preference in the selection of the pedal, latency of pressing the pedal and the number of omitted reactions were estimated. It was found that "impulsive" animals more rapidly pressed the pedal and less frequently omitted trials than "self controlling" rats. After the increase in the delay duration up to 7 seconds, rats stopped choosing the pedal with the delayed reinforcement. Increased food motivation shifted the behavior of rats to "self-control", whereas rats after feeding preferred less valuable immediate reinforcement. PMID- 20352685 TI - [Sound signals of danger activate the nitrergic system of the medial nucleus accumbens]. AB - It was shown in Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis that presentations to the animals in a home cage of a tone previously paired with a footshock in an experimental chamber produced an increase in extracellular levels of citrulline (an NO co-product) in the medial n. accumbens. The increase was prevented by intraaccumbal infusions of 7 nitroindasole (0.5 mM), a neuronal NO synthase inhibitor and was not observed in rats previously exposed to unpaired tone and footshock presentations and in controls with microdialysis probes implanted into the lateral n. accumbens. The results indicate that sound signals of danger produce a neuronal NO synthase activation within the medial n. accumbens, which leads to citrulline formation and, very likely, to NO production in this brain area. PMID- 20352686 TI - [Social preference of white rats with high and low anxiety]. AB - In outbred population of white rats (Rattus norvegicus), we picked out two groups of male animals with high (HA) and low levels of anxiety (LA). Social preference for a familiar or unfamiliar conspecific were studied. The rats (n = 85) were housed five per cage for two months before the experiment. Thus, the social structures in every cage were stable. The anxiety was tested in an elevated plus maze. For social interaction test we used the box, in which two opposite corners were separated with perforated transparent Plexiglas walls. A mate of a tested subject was placed into one corner the cage, an unfamiliar animal was put into another corner. During five minutes we measured the time spent near each of the conspecifics and in neutral area. For both high- and low-anxiety groups, the time spent in the neutral area was less than 60 sec. i.e. rats in a novel environment spent much more time in social contacts than in environmental exploration. Rats with high anxiety spent 88 +/- 32 s and 155 +/- 35 s close to an unfamiliar subject and a cage mate, respectively. On the contrary, the measurements for rats with low anxiety were 200 +/- 40 s for an unfamiliar subject, and 65 +/- 32 s for a cage mate. Consequently, high-anxiety rats preferred contacts with a familiar conspecific, whereas low-anxiety rats preferred to contact with an unfamiliar conspecific. PMID- 20352687 TI - [Mechanisms of synchronization in local neural networks of neocortex. Modelling and experimental researches]. AB - We investigated parameters of excitation and inhibition in neurons of a visual cortex of a cat. On somatosensory cortex of rats temporary parameters ofepileptiform activity were investigated. The experimental results received have been used for construction of imitating model of a neural network by means of program of "Neuroimitator" for research of mechanisms of synchronization in a neural network. The neural network consisted from 30 neurons. The temporary parameters of excitation and inhibition were different. Two conditions of a neural network in the model were used. In the first case activity of every neuron was spontaneous, and in the second case the activity represented cycles of excitation--inhibition. Synchronization (simultaneous activity of the neurons) at the ordered time structure of excitation and inhibition cycles was considerably higher, than during the spontaneous activity. The results received show, that at strengthening the inhibition, the synchronization in local neural networks increases. The greater amplitude of field potential can be a direct reflection of synchronous activity of the elements of nervous system not connected with each other. PMID- 20352688 TI - [The blocade of glutamate metabotropic 5-th tipe receptors prevents the locomotor behavior changes produced by intrastriatal picrotoxin microinjections in rats]. AB - It was demonstrated in chronic experiments in Wistar rats that only the first of daily multiple microinjections of glutamate metabotropic 5-th type receptor antagonist MTEP into the rostral region of neostriatum impaired the avoidance conditioning in a shuttle box. Within the next two weeks, MTEP was ineffective but being injected into the neostriatum simultaneously with picrotoxin prevented the impairment of avoidance conditioning in a shuttle-box and decreased the hyperactivity (open-field locomotor hyperactivity and choreic hyperkinesis) produced by this GABA-A receptor antagonist. The results do not suggest the involvement of striatal glutamate metabotropic 5-th type receptors in avoidance conditioning control but demonstrate that glutamate metabotropic system is involved in behavioral disorders mediated by inhibition of GABA-A receptors. In principle, it might be possible to treat the human hyperkinetic basal ganglia dysfunction (Huntington's horea), athetosis and similar disorders with glutamate metabotropic receptor antagonists. PMID- 20352689 TI - [Effect of selective serotonin reuptake inhibitor fluoxetine on symptoms of depression-like behavior in WAG/Rij rats]. AB - A possibility to correct behavioral symptoms of depression-like behasior in WAG/Rij rats with selective serotonin reuptake inhibitor antidepressant drug fluoxetine was studied. The efficacy of fluoxetine was compared with that of tricyclic antidepressant imipramine. Vehicle-treated WAG/Rij rats compared with the corresponding group of Wistar rats exhibited symptoms of depression-like behavior: a decreased level of exploratory activity and grooming reactions in the open field test, increased immobility in the forced swimming test, and decreased sucrose intake and preference (anhedonia). Differences in anxiety level in the light-dark choice test between WAG/Rij and Wistar rats were not found. Chronic injection of fluoxetine (5 mg/kg, i.p., for 15 days) didn't exert substantial influence on the anxiety level in the light-dark choice test both in WAG/Rij and Wistar rats. In the open field test, fluoxetine didn't significantly affect behavior of "depressive" WAG/Rij rats but induced anxiogenic effect in "normal" Wistar rats (a decrease in the number of center entries and an increase in the number of grooming reactions). In the forced swimming test, fluoxetine induced antidepressant effect (a decrease in immobility time and increase in the time of swimming) statistically significant in Wistar rats and at the level of tendency in WAG/Rij rats. In the sucrose consumption test, fluoxetine enhanced sucrose intake in "depressive" WAG/Rij rats and induced a tendency to a decrease in sucrose intake in "normal" Wistar rats. Fluoxetine didn't change sucrose preference (%) both in WAG/Rij and Wistar rats. In "depressive" WAG/Rij rats, selective serotonin reuptake inhibitor antidepressant fluoxetine was less effective than tricyclic antidepressant imipramine. However, a therapeutic effect of imipramine was apparent only after the cessation of chronic treatment. During treatment, worsening ofbehavioral characteristics was seen not only in "normal" Wistar rats but to an even greater degree in "depressive" WAG/Rij rats. Fluoxetine caused worsening of some behavioral characteristics only in "normal" Wistar rats. In "depressive" WAG/Rij rats, the therapeutic effect offluoxetine developed earlier than that of imipramine and was not accompanied by an adverse side effect on behavior of animals. PMID- 20352690 TI - [Study of extracellular concentration of dopamine and its metabolites in mice striatum by a microdialysis technique at intraperitoneal administration of MPTP]. AB - In this paper a structure of a microdialytic cannula inserted into brain areas just before a microdialysis is described. The cannula used allowed to find out a correspondence of behavioral and biochemical changes in C57BL/6 mice at various time intervals after a single dose administration (20 mg/kg) of the neurotoxin, 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine, without any additional pharmacological actions enhancing an extracellular striatal dopamine concentration. Immediately after 1-methyl-4-phenyl-1.2,3.6-tetrahydropyridine administration an essential disturbance of mice behavior and a significant reduction of the extracellular concentration of dopamine and homovanillic acid were observed in striatum. A week after the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine administration neither behavior nor the extracellular dopamine and homovanillic acid striatal concentration substantially differed from those of controls. 30 days after the neurotoxin administration there was again an essential disturbance of behavior and the large reduction of dopamine and its metabolite concentration in striatum. There was suggested that a reduction of the dopamine concentration immediately after 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine injection connected with abnormalities of dopamine synthesis and metabolism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine whereas a reduction of the extracellular striatal dopamine concentration 30 days after 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration related to damage of the nigrastriatal dopaminergic system. PMID- 20352691 TI - [Is "fibroblast" a specialized cell or a functional condition of mesenchymal cells derivatives?]. AB - The debatable article is devoted to the analysis of consecutive changes of the notion about the origin, migration, morphofunctional heterogeneity, differentiation and proliferative potential of the basic cells of a connective tissue--fibroblasts. Despite of a plenty of an actual material on this section of cellular biology, till now there is no uniform concept about fibroblasts to a full degree defining their cytogenesis, features of phenotypic answers, and position in differon organization. In this article, the data available in literature are systematized and generalized. The modern outline of fibroblastic differon is offered for the subsequent determination of role and place of its various parts in normal physiological and pathological reactions of connective tissue. PMID- 20352692 TI - [Development of ovarioles and nurse cells cytoskeleton in Calliphora erythrocephala Mg. (Diptera; Calliphoridae)]. AB - We have carried out the analysis of ovariole development and morphology in Calliphora erythrocephala Mg. (Diptera: Calliphoridae). It has been shown that several regions can be distinguished in C. erythrocephala germarium. In these regions cyst morphogenesis goes on stage by stage right up to the separation of formed egg chamber. There are fusomes of different degree of branching in germarium. Two egg chambers develop in C. erythrocephala vitellarium. We have researched distribution of actin filaments and ring canals formation in the nurse cells of C. erythrocephala. Diameter of ring canals increases from 1.5 microm in germarium zone to 14.7 microm at 3 and 4 stadies oogenesis. We suggest the scheme that illustrates irregular stretching of actin rollers which are formed during middle and late oogenesis around the ring canals joining proximal, sharply increased in size nurse cells with neighboring nurse cells. PMID- 20352693 TI - [Membrane contacts of endoplasmic reticulum with plasmalemma in plant cells]. AB - Close contacts of endoplasmatic reticulum membrane with plasmalemma have been shown in common wheat root cells by means of electron microscopy. Qualitative analogy of these contacts with high-permeable intercellular contacts in animals has been preliminary established. PMID- 20352694 TI - [The influence of solcoseryl on population and cellular parameters of HeLa and RD cultures]. AB - Changes of population and cellular parameters of HeLa and RD cultures after introducing of solcoseryl in culture medium were studied by methods of scanning cytophotometry and cytomorphometry. Monolayer density, proliferation activity, the number of dead cells in a monolayer, the number of nucleoli in nuclei and distribution of cells in the populations by this parameter, RNA and DNA masses in nuclei and nucleoli, total volumes and surface areas of the nuclei and nucleoli were determined. It has been shown that solcoseryl differently affects the cultures both on population and on cellular levels of their organization. The results of multi-parametric analysis of the influence of solseryl on the cultures allow considering it as a biologically active compound with the features typical for cell and cell population growth regulating factors. PMID- 20352695 TI - [Variations in cell population size and reactive oxygen species level in the blood and the ascites liquid of tumor carrier]. AB - Using Seidel ascites hepatoma as a model, we studied in detail changes in cell population size and in the level of reactive oxygen species in the tumor growth zone and in the blood plasma of tumor carrier. It was found that reduction oxidation conditions in the blood plasma and in the tumor growth zone were different. Thus, because of hyperactivity and increase in the number of leukocytes, the blood plasma exhibited strong oxidative stress inducing damage to healthy cells, whereas the tumor growth zone showed the decrease in macrophage concentration, as well as in oxygen and ROS levels. These conditions favor intensive growth of tumor cells. PMID- 20352696 TI - [Analysis of chromosome composition in interspecific embryonic stem hybrid cells of mice]. AB - Chromosome complements of twenty hybrid clones obtained by fusion of Mus musculus embryonic stem cells (ESC) and M. caroli splenocytes were studied. Using of double-color in situ hybridization with chromosome- and species-specific probes we were able to detect the parental origin for each chromosome in hybrid cells. Based on parental chromosome ratio, all 20 hybrid clones were separated in some different groups: from the group containing practically tetraploid M. musculus genome with single M. caroli chromosomes to hybrids with dominance of M. caroli chromosome homologues. In 8 hybrid cells clones we observed prevalence of chromosomes originated from ESC in ratio from 5:1 to 3:1. Another hybrid cells clones have either equal (1:1, 1:2) ratio of M. musculus to M. caroli chromosomes or with the prevalence of ESC- (2:1) or splenocyte- (1:2) originated parental chromosome homologues. In 3 hybrid cells clones, we observed preferable segregation of ESC-originated pluripotent chromosomes. This phenomenon was found for the first time and it possibly indicates compensation of the epigenetic differences between parental chromosomes of ESC- and splenocyte-origination. PMID- 20352697 TI - [Viability and angiogenic activity of mesenchymal stromal cells from adipose tissue and bone marrow in hypoxia and inflammation in vitro]. AB - Adult progenitor stromal cells derived from adipose tissue (ADSC) and bone marrow (BMDSC) hold great promise for use in cell-based therapy of ischemic diseases. Both cell lines secrete a various number of angiogenic cytokines which are regulated by hypoxia and improve vascularization of ischemic tissues being injected in damaged muscle or intravenously. However, such factors as low oxygen level and inflammation may impair the viability and functional activity of these cells after delivery to the ischemic area. We directly compared the reactions of ADSCs and BMDSCs to hypoxic and inflammatory conditions in vitro. Cultured ADSCs and BMDSCs from Balb/c mice were cultivated for 48 h under 1% O2 (hypoxia), 20% O2 (normoxia) or in the presence of inflammatory cytokines. Cell viability analyzed by annexin V-PE binding and 7AAD storage (flow cytometry), and by quantitative TUNEL showed no decrease under hypoxic condition. But cell apoptotic rates significantly increased (up to 70 %) under inflammatory condition. Inflammatory cytokines did not stimulate gene expression of angiogenic growth factors. Otherwise, gene expression profiles of angiogenesis-related cytokines showed activation of pro-angiogenic and suppression of anti-angiogenic factors in the cells under hypoxic condition. In general this effect was higher for ADSCs than for BMDSCs. Using in vitro and in vivo models of angiogenesis we have demonstrated that incubation under hypoxic condition increases stromal cells ability to stimulate blood vessels growth. PMID- 20352698 TI - [Characteristics of chromatin structural organization in somatic nucleus of the ciliate Didinium nasutum]. AB - Structural organization of macronuclear chromatin of the ciliate Didinium nasutum was studied. Macronuclear genome of D. nasutum is represented by DNA molecules of subchromosomal size. At interphase, macronuclear chromatin is organized into chromatin clumps approximately 100-200 nm in size and some of them form short thick fibres consisting of several chromatin clumps. Using differential staining of nucleic acids on ultrathin sections we revealed perichromatin fibres and granules on the surface of many chromatin clumps. 3D models of spatial distribution of chromatin clumps in the macronucleus were reconstructed on the basis of serial ultrathin sections and peculiar features of their organization were studied. PMID- 20352699 TI - [Karyological characteristics of Abies sibirica in the Middle Siberia]. AB - Data on Abies sibirica karyotype structure have been obtained in five populations of Middle Siberia. Chromosome set (2n = 24) consists of 7 pairs of metacentric (I -VII), 4 pairs of submetacentric (VIII, X-XII) and a pair of intercentric (IX) chromosomes. Morphometric parameters of chromosome groups are similar in the populations studied. Variation of Abies sibirica chromosome characteristics is low. Intraspecific chromosome polymorphism of A. sibirica is substantially connected with variation of the number of NOR-chromosome in the karyotype and with location of NOR in chromosome arms. Mixoploidy, somatic reduction of chromosomes, and a triploid seedling of A. sibirica have been registered on the territory with antropogenic press. PMID- 20352700 TI - [Different regulation of mitochondrial apoptosis and Bcl-2 gene expression in quescent and proliferative human fibroblasts infected with cytomegalovirus]. AB - The aim of the study was to compare the dynamics ofmitochondrial apoptosis (MA) in cells at different stages of proliferation and with different susceptibility to cytomegalovirus (CMV). It has been found that in quiescent human fibroblasts (HF) CMV regulates MA at the level of bcl-2 gene transcription, exerting both pro and anti-apoptotic effects. Suppression of bcl-2 transcription is greater in HF 977 line, which is highly susceptible to CMV in comparison with HF-1068 line. The effect of proliferative activity on MA was studied using CMV-infected HF-110044 line at the G0- or S-phase. A direct correlation was established between accumulation of cytochrome c and caspase 3 (MA markers) and production of IE72, pp65 and gB (CMV proteins). In G0-fibrob-lasts, viral replication was highly productive and bcl-2 expression was 10-fold as high as in S-phase cells, in which viral protein production and cell death were much lower. The increased gene transcription and accumulation of Bcl-2 protein enhanced cell viability and provided synthesis of viral proteins. Impaired structure of actin microfilaments, a caspase 3 target, coincided with pronounced suppression of gamma-actin gene in S-phase HF-110044. Our findings provide an insight into CMV-induced mechanisms of MA which lead to rapid death of infected quiescent fibroblasts and to slow death of cells infected at the stage of DNA synthesis. PMID- 20352701 TI - [Functional state of adenylyl cyclase signaling system in reproductive tissues of rats with experimental type 1 diabetes]. AB - Diabetes mellitus (DM) of type 1 induces numerous disturbances in reproductive systems of males and females. We have shown earlier that the main cause of the complications in the case of DM is alteration of adenylyl cyclase signaling system (ACSS) sensitivity to hormones. The aim of the present work was identification of disturbances in hormone-regulated ACSS in reproductive tissues of rats with experimental type 1 DM (EDM1) induced by streptozotocin treatment. Testis of the rats with 5-days EDM1 showed significant decrease in the stimulatory effects of human chorionic gonadotropin (hCG) and PACAP-38 on adenyly] cyclase (AC) activity and G protein GTP-binding. Uterus of the rats with EDM1 exhibited decreased effects of relaxin, PACAP-38 and biogenic amines. In the ovaries, we showed the decrease in hCG effects only. Weakening of the inhibitory influence of somatostatin on ACSS activity was found in all studied tissues of rats with EDM1. Uterus displayed also decreased inhibitory effects of serotonin and adrenaline. Thus, regulatory effects of the hormones in ACSS sensitivity in reproductive tissues of the rats with EDM1 were decreased. The effects of hCG and AC inhibiting hormones were decreased to a greater extent. We suppose that the decrease in ACSS sensitivity to hormones in the case of EDM1 is responsible for pathological changes in reproductive systems of diabetic rats under condition of hyperglycemia and insulin deficiency which are typical for type 1 DM. PMID- 20352702 TI - [Specific function of STAT5 in regulation of proliferation of chronic leukemia K562 cells: inhibitory effect of WHI-P131]. AB - In this study, we examined the possible role of JAK/STAT signaling pathway in regulation of proliferation of chronic leukemia cells K562. The thyrosine phosphorylation of STAT3 and STAT5 was used as a marker of an activation status of STAT proteins. We demonstrate that in growing culture of K562 both STAT3 and STAT5 are constitutively activated. To determine the significance of STATs activity in maintaining the high level of K562 proliferation we tested two JAK inhibitors: AG-490 (JAK2 and JAK3 inhibitor) and WHI-P131 (a new specific JAK3 inhibitor). We showed that in long-tern cultures (48 h) of K562 cells with AG-490 or WHI-P132 the cells remain viable. It was found that treatment with WHI-P131 (30-100 microM) decreased the thyrosine phosphorylation of STAT5 being without effect on the high level of STAT3 phosphorylation. In proliferating K562 cells, AG-490 (25-50 microM) did not influence STAT3 and STAT5 phosphorylation. The flow cytometry analysis revealed a dose-dependent decrease in G1 and S phases and an increase in G2/M phases in WHI-P131-treated K562 cell cultures and no changes in cell cycle structure in AG-490-treated cells. Thus, our findings indicate a preferential role for STAT5 (not constitutively active STAT3) in proliferation of leukemia to other JAK drugs which stimulate apoptosis and decrease proliferation, WHI-P131 prevents K562 cells growth by arresting in G2/M phases of cell cycle. PMID- 20352703 TI - The effects of dimensionality on electrochemical sensors based on carbon nanotubes and metallic nanowires. AB - Electrochemistry based unidimensional nanoelectrodes, such as carbon nanotubes and metallic nanowires, is now a reality that is leaving the academy and reaching a broad range of high-tech companies around the world. The intrinsic properties of electron-electron interactions, sizes and geometries significantly differentiate those nanostructures from conventional macroelectrodes or electrodes with sizes in a millimetric range. The inherent properties as well as the configuration of carbon nanotubes and metallic nanowires as electrochemical sensors are the main focus of this review. Applications and some future trends on developing of a clear pathway for assembly and integration of these into functional materials, are summarized as well. PMID- 20352704 TI - Self-assembly of colloidal nanoscale particles: fabrication, properties and applications. AB - Self-assembly is a spontaneous process by which molecules to macroscopic entities assembled into one-, two- and three-dimensional ordered array. Even though, much attention has been focused on molecular self-assembly, numerous fascinating applications of self-assembling processes can be found at nanoscale to microscale level. Well-defined ordered structures prepared through the self-assembly of colloidal nanoscale to microscale particles, provide new opportunities for optimizing, tuning and/or enhancing the properties and performance of the materials. In this review, we have provided a concise and comprehensive account of the latest research and development activities in the fabrication, properties and applications of self-assembled structures from colloidal building blocks of various metals, semiconductors, oxides and polymers. The applicability, limitations and potential of different self-assembly techniques are also discussed. PMID- 20352705 TI - Model for hyperthermia with arrays of magnetic nanoparticles: spatial and time temperature distributions in tumor. AB - A square array of micron-sized needles containing magnetic nanoparticles has been studied theoretically as potential systems to deliver heat to tumor tissue for the hyperthermia treatment. The spatiotemporal distributions of temperature in a tumor were calculated for different arrays of microneedles. The resulting temperature distributions are found to be more uniform within the tumor target than those caused by other heating systems. Moreover, the temperature profiles could be tuned by a proper choice of the combination of the system parameters: the needle radius, the spatial needles period, as well as the filling fraction and parameters of magnetic nanoparticles. PMID- 20352706 TI - Chemiluminescent detect of E. coli O157:H7 using immunological method based on magnetic nanoparticles. AB - The system of chemiluminescent magnetic enzyme-linked immunoassay was developed. E. coli O157:H7 was sandwiched between rabbits anti-E. coli O157:H7 polyclonal antibody-coated magnetic nanoparticles (immunomagnetic nanoparticles or IMNPs) and mouse anti-E. coli O157:H7 monoclonal antibody. Commercial alkaline phosphatase conjugated horse anti-mouse immunoglobulin (ALP-Ab) was used to bind with the monoclonal antibody, finally the chemiluminescent signals were detected by adding 3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)phenyl-1,2 dioxetane (AMPPD) which was the substrate reagent of ALP. Different solvents of AMPPD were compared to get an optimal chemiluminescent signal. The effects of sodium borohydride and glycine on blocking the aldehyde groups of IMNPs were compared either, and the specificity and sensitivity of this system for detecting E. coli O157:H7 were researched. The results indicated that Tris buffer was the best solvent of AMPPD, sodium borohydride was better than glycine in blocking IMNPs, and this method was of good specificity when using E. coli Top 10F' and Vibrio cholera as negative controls. The detection limit was 10(3) cells mL(-1) when the antigen solution was 1 mL, and the procedure duration was about 3 h. PMID- 20352707 TI - Functionalized multi walled carbon nanotubes nano biocomposite film for the amperometric detection of L-cysteine. AB - The development of nano biocomposite film (f-MWCNTs-Au-GO(x)) for L-cysteine (LC) detection is proposed by using glassy carbon electrode (GCE). The proposed nano biocomposite film has been fabricated on ITO for scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis. Next, the f-MWCNTs-Au-GO(x) nano biocomposite film modified GCE's surface was examined by scanning electrochemical microscopy (SECM). The proposed nano biocomposite film has been successfully applied for the detection of LC using cyclic voltammetry (CV) and amperometry. The f-MWCNTs-Au-GO(x) film modified GCE exhibited a linear response for LC detection in the lower and higher concentrations ranges of 2 to 42 x 10( 6), 0.1 to 1.08 x 10(-3) mol L(-1). Also, the proposed nano biocomposite film possesses high sensitivity and good repeatability for LC detection. PMID- 20352708 TI - Preparation and characterization of n-hydroxyapatite/PCL-pluronic-PCL nanocomposites for tissue engineering. AB - In this paper, a new kind of polymeric nanocomposite materials based on nano hydroxyapatite (n-HA) and PCL-Pluronic-PCL (PCFC) copolymer were prepared by in situ combination method. Firstly, the PCFC copolymer was synthesized by ring opening polymerization of epsilon-caprolactone initiated by Pluronic (PEG-PPG PEG); Secondly, n-HA powder were combined with PCFC to form polymeric composites in the presence of hexamethylene diisocyanate (HDI). The obtained composites were characterized by 1H-NMR, FTIR, XRD, TEM, SEM, DTA/TGA, and tensile testing. The results revealed that n-HA could be dispersed into polymer matrix uniformly, and the n-HA/PCFC composite showed great mechanical properties when the content of n HA was 10 wt%. The microstructure and thermal properties of the composites were discussed in the paper too. The experimental results suggested that this polymeric nanocomposite might have great potential application in the field of tissue engineering. PMID- 20352709 TI - Nanoscale sensor design via in situ labeling of gold nanoparticles onto protein scaffolds. AB - A one-step method for synthesis of bioconjugated gold nanoparticles is reported. A non-toxic and biocompatible phosphorus based reducing agent was used for reduction of gold (III) and formation of nanoparticles. Physicochemical properties of protein-A stabilized gold nanoparticls were investigated. Result of immunoassay experiments confirmed the potential of the synthesized anti-protein-A conjugated gold nanoparticles for use as a simple and inexpensive test for quantitative screening of protein-A samples. PMID- 20352710 TI - A new isolate of Iris severe mosaic virus causing yellow mosaic in Iris ensata Thunb. AB - Severe mosaic disease was observed on Iris ensata Thunb. in Spring 2008, in Hangzhou, China and it was found to be widely distributed in that region. Detection of viruses by electron microscopy resulted in the occurrence of a potyvirus in most symptomatic seedlings. Sequencing 1745 nucleotides of the 3' terminal region of the genome of the typical viral isolate revealed that it was a new isolate of Iris severe mosaic potyvirus (ISMV), tentatively named ISMV-PHz .This strain shared high nucleotide identity with ISMV. Phylogenetic analysis also showed that this isolate clustered with iris severe mosaic potyvirus (ISMV) and onion yellow dwarf virus (OYDV) into a monophyletic group, and was closest in similarity to ISMV. The divergence of potyvirus-infecting iris species had a higher degree of relevance with natural host but not with the region from which it was isolated. This is the first report of ISMV isolated from I. ensata in China. PMID- 20352711 TI - Solvothermal synthesis and characterization of Eu3+ doped Y2O3 nanocrystals. AB - A solvothermal refluxing system containing of ethylene glycol and ethylene glycol hexane mixed organic solvents were used to prepare Eu3+ doped Y2O3 nanocrystals via solvothermal refluxing reaction-calcinations method. In the presence of ethylene glycol, the reaction temperature required for the preparation of Y(OH)3 precursor crystal is 170 degrees C but in ethylene glycol-hexane mixed organic solvents, the synthesis temperature was reduced to 70 degrees C. The Y(OH)3 precursor particles were calcinated at 600-1200 degrees C in air to prepare nanosized Eu3+ doped Y2O3 red phosphor. The as prepared particles by refluxing in ethylene glycol followed by calcination showed 20-60 nm in diameter. For the characterization, XRD, TG-DTA, EDS, FTIR, TEM and PL measurements were employed. The as prepared sample by refluxing in ethylene glycol-hexane mixed solvents exhibited strong red emission around 610 nm under 254 nm xenon light excitation and photoluminescence property was compared with reference sample (5 mol% Eu3+:Y2O3) prepared via conventional co-precipitation method followed by calcinations at 800 degrees C for 5 h in air. PMID- 20352712 TI - Effects of vacancy defects on the interfacial shear strength of carbon nanotube reinforced polymer composite. AB - We investigate the effects of the vacancy defects (i.e., missing atoms) in carbon nanotubes (CNTs) on the interfacial shear strength (ISS) of the CNT-polyethylene composite with the molecular dynamics simulation. In the simulation, the crystalline polyethylene matrix is set up in a hexagonal array with the polymer chains parallel to the CNT axis. Vacancy defects in the CNT are introduced by removing the corresponding atoms from the pristine CNT (i.e., CNT without any defect). Three patterns of vacancy defects with three different sizes are considered. Two types of interfaces, with and without cross-links between the CNT and the matrix are also considered here. Polyethylene chains are used as cross links between the CNT and the matrix. The Brenner potential is used for the carbon-carbon interaction in the CNT, while the polymer is modeled by a united atom potential. The nonbonded van der Waals interaction between the CNT and the polymer matrix and within the polymer matrix itself is modeled with the Lennard Jones potential. To determine the ISS, we conduct the CNT pull-out from the polymer matrix and the ISS has been estimated with the change of total potential energy of the CNT-polymer system. The simulation results reveal that the vacancy defects significantly influence the ISS. Moreover, the simulation clarifies that CNT breakage occurs during the pull-out process for large size vacancy defect which ultimately reduces the reinforcement. PMID- 20352713 TI - Shape-controlled synthesis of triangular gold nanoprisms using microwave irradiation. AB - In this report, we described the very fast synthesis of gold nanoprisms under microwave heating for 60-90 s in the presence of 2-naphthol (2-N) as a new reducing agent. The growth of the particles with different shapes (spherical, polygonal or triangular/prisms etc.) were found to be functions of the surfactant to-metal-ion molar ratio and the concentration of 2-N. The evolved nanoprisms were approximately 110 +/- 10 nm in diameter and the particles size and shape was successfully tuned just by varying the molar ratio of the reactants. This process can be extended to the synthesis of other nonmaterial with desired sizes and shapes. The method we generated might find variety of application in many areas such as catalysis, clinical and diagnostic medicine, and nanoelectronics. PMID- 20352714 TI - Stability of embedded indium nanoclusters in silica under thermal treatment and ion irradiation. AB - The stability of embedded Indium (In) nanoclusters (NCs) in silica under thermal annealing and ion irradiation was investigated. The In NCs were prepared by implantation of 890 keV indium ions in silica matrix at room temperature. Post implantation annealing resulted in the shifting of the size distribution to higher side. On the other hand 140 keV Nitrogen ion irradiation at elevated temperature resulted in the reduction of NCs size, with significant narrowing of the size distribution. The paper discusses the results of the study in the light of the models pertaining to the stability of NCs under ion irradiation conditions. PMID- 20352715 TI - Effect of nanocomposite gate-dielectric properties on pentacene microstructure and field-effect transistor characteristics. AB - In this study, the effect of surface energy and roughness of the nanocomposite gate dielectric on pentacene morphology and electrical properties of pentacene OTFT are reported. Nanoparticles TiO2 were added in the polyimide matrix to form a nanocomposite which has a significantly different surface characteristic from polyimide, leading to a discrepancy in the structural properties of pentacene growth. A growth mode of pentacene deposited on the nanocomposite is proposed to explain successfully the effect of surface properties of nanocomposite gate dielectric such as surface energy and roughness on the pentacene morphology and electrical properties of OTFT. To obtain the lower surface energy and smoother surface of nanocomposite gate dielectric that is responsible for the desired crystalline, microstructure of pentacene and electrical properties of device, a bottom contact OTFT-pentacene deposited on the double-layer nanocomposite gate dielectric consisting of top smoothing layer of the neat polyimide and bottom layer of (PI+ nano-TiO2 particles) nanocomposite has been successfully demonstrated to exhibit very promising performance including high current on to off ratio of about 6 x 10(5), threshold voltage of -10 V and moderately high filed mobility of 0.15 cm2V(-1)s(-1). PMID- 20352716 TI - ToF-SIMS study of carbon diffusion in Co-Pt-TiO2 composite and ruthenium films. AB - In this paper, the diffusion behavior of hydrogenated amorphous carbon into Co-Pt TiO2 and Ruthenium films was first investigated. Impact of carbon on Co-Pt-TiO2 composite film and its diffusion in Co-Pt-TiO2 and ruthenium films were studied using Time-of-Flight Secondary Ion Mass Spectroscopy. Magnetic coercivity drop was observed for Co-Pt-TiO2 films coated with ruthenium and carbon hybrid overcoat at varied thickness ratio. Co-Pt-TiO2 film is widely used in perpendicular magnetic recording. Carbon depth profile showed that carbon readily diffuses in Co-Pt-TiO2 film because of its porous structure. However, carbon diffusion in ruthenium film is limited even annealing up to 200 degrees C in argon. Carbon's diffusion length and coefficient in Co-Pt-TiO2 are much higher than that in Ru film. The activation energy was calculated for both cases. PMID- 20352717 TI - Cu-Au-Ag alloy nanoparticles incorporated silica films using a new three-layer deposition technique. AB - Formation of Au-Ag-Cu ternary alloy nanoparticles (NPs) is difficult mainly because the system Cu/Ag is immiscible. We present a new synthetic technique to generate such ternary alloy NPs in silica film matrix employing a three-layer (3L) coating design. In this methodology three successive coating layers were deposited on silica glass substrates from separately prepared Cu-, Au- and Ag-ion incorporated inorganic-organic hybrid silica sols by dipping method. The Au layer is kept in the middle because it is miscible with both the Ag and Cu. The 3L film assembly was subjected to UV- and heat-treatment at 450-750 degrees C in H2-N2 atmosphere. UV-treatment generates small Au and Ag NPs in the respective layers and Cu remains as Cu2+; subsequent heat-treatment in H2-N2 induces the formation of ternary alloy NPs by the interlayer diffusion of nanometals. The final heat treated film (750 degrees C/H2-N2) shows single and sharp plasmon band centered at 480 nm in the UV-visible spectrum indicating the formation of alloy (solid solution) NPs. GIXRD study shows one set of diffraction peaks which are shifted towards higher angle with respect to the Au or Ag diffraction peaks. FESEM, GIXRD, HRTEM, and SAED analyses reveal that the alloy has a composition close to (Au + Ag)0.88Cu0.12. The EDS analyses using the nano probe attached with TEM confirm the presence of Au, Ag and Cu in all the alloy NPs. PMID- 20352718 TI - Long nanofibers arrays through surfactant self-assembly. AB - Self assembly of molecules can be a simple and versatile approach that may lead to nanostructures. Here we report the formation of arrangements of exceptionally long nanofibers of cationic surfactant hexadecyltrimethylammonium bromide molecules with highly defined spatial and parallel ordering. Arrangements of approximately 1 microm long nanofibers were observed by non-contact atomic force microscopy. The long nanofiber patterns form structures in approximately 5 x 5 microm2 regions and consist of approximately 6 nm wide lines. The formation mechanism of the fibers is shown to be the coalescence of isolated surfactant micelles (approximately 3.2 nm diameter in solution) in the convection stream of the surfactant solution drop close to the pinned contact-line region during drying. The size of micelles formed in solution determines the diameter of the deposited fibers. New deposition schemes of micelles forming nanorods on bare silicon previous to the formation of surfactant bilayers are now being investigated based on the data obtained in this work. PMID- 20352719 TI - Effects of dipolar interaction on magnetic properties of Fe(x)(SiO2)1-x nanocomposites. AB - The effects of dipolar interaction on the magnetic properties of the Fe(x)(SiO2)1 x nanocomposites (22 wt% < or = x < or = 51 wt%) synthesized by mechanochemical reduction reaction have been studied by Mossbauer spectroscopy and magnetic measurements. As the average particle size of the Fe particles in the Fe(x)(SiO2)1-x nanocomposites changes very little with increasing Fe content x, the dipolar interaction strength can be tuned by adjusting the distance between the Fe particles through controlling the Fe content x. Thus the effects of dipolar interaction on the magnetic properties of the Fe(x)(SiO2)1-x nanocomposites can be clearly studied. Due to the dipolar interaction, the Fe particles transit from superparamagnetic state to the blocked state. With x increasing from 22 wt% to 48 wt%, due to dipolar interaction, the Fe particle moment arrangements change from random orientation to ordered arrangements, which induced an additional anisotropy, leading to the increase in the coercivity H(c) and remanence ratio M(r)/M(s). For x increasing beyond 48 wt%, the dipolar interaction strength further increases, and the Fe particle moment arrangements tend to form the flux-closure configurations in order to reduce the dipolar interaction energy among the particles, which result in the decreases of H(c) and M(r)/M(s) with increasing x. PMID- 20352720 TI - Quaternary ZnCdSeTe nanowires. AB - We report the growth of needle-like high density quaternary ZnCdSeTe nanowires on oxidized Si(100) substrate using vapor-liquid-solid mechanism by molecular beam epitaxy with an Au-based nanocatalyst. It was found that average length and average diameter of the nanowires were 1.3 microm and 91 nm, respectively. It was also found that the as-grown ZnCdSeTe nanowires exhibit mixture of cubic zinc blende and hexagonal wurtzite structures. Energy depersive results indicate that composition ratio of our nanowire should be Zn0.87Cd0.13Se0.98Te0.02, which agrees excellently with the designated composition ratio of Zn0.87Cd0.13Se0.98Te0.02. PMID- 20352721 TI - Two-dimensional organization of mono- and bisurea supramolecular polymers studied by scanning tunneling microscopy. AB - Scanning tunneling microscopy (STM) of mono- and bisurea-functionalized oligo(p phenylenevinylene)s at solid/liquid interface visualized two-dimensionally ordered double columnar structures of pi-conjugated segments scaffolded by one dimensional supramolecular polymerization of urea hydrogen-bonding units. In contrast to a persistent alignment of the bisurea compound supported by twofold intermolecular urea-urea hydrogen-bonding, the building blocks in the monourea double columns shows dynamic fluctuation and defects because of their rotational motion around urea-urea hydrogen-bonding axis and/or adsorption-desorption of the individual molecules from the surface. Self-assembled structures of mono- and bisurea compounds at solid/liquid interface revealed by STM can be related to their gelation abilities in organic solvents. PMID- 20352722 TI - DFT study on the interactions between Au(n) (n = 2...4) and adenine. AB - Binding of gold clusters with adenine was studied using density functional method (DFT). Geometries of neutral adenine with Au(n) (n = 2, 3 and 4) clusters were optimized using the B3LYP approach. The 6-31G+(d, p) basis set was used for adenine and the Stuttgart/Dresden effective core potential (ECP) basis set SDD was employed for the gold atom. Structural parameters and energy properties were discussed for the optimized complexes stabilized with the anchoring Au-N and the nonconventional Au...H-N hydrogen bond. The calculated interacting energy results show that the binding of Au(n) is the most strong at N3, whereas its binding at N6 displays relatively weaker stability. Furthermore, analysis of the charge distributions of the optimized complexes by using the natural bond orbital analysis indicates charge is transferred from the lone pair of nitrogen in adenine to the n* and sigma* orbitals of Au during the interaction between the Au(n) and adenine. The calculated second-order perturbation stabilization energies show that the interaction Au-N anchoring bond plays an important role compared with the nonconventional Au...H-N hydrogen bond. PMID- 20352723 TI - Nanoparticle induced conformational change in DNA and chirality of silver nanoclusters. AB - Nano-clusters formed on macromolecular templates carry the symmetry information of the template. Templates with broken symmetry thus lead to formation of asymmetric clusters. In response, such clusters induce a compensatory stress on the embedded template. Silver nanoparticles grown on a covalently closed negatively supercoiled plasmid DNA (pUC19) exhibit chiral behavior and as a reciprocal response, one observes alteration in DNA conformation. The inference was drawn using gel mobility-shift studies in which a silver nanoparticle (but not ions) induces a mobility shift implying a drift from supercoiled to relaxed state of the plasmid. Supporting evidences for such structural alterations were obtained from circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR). Silver ion and silver nanoparticles induce differential FT-IR signals reflected in the fingerprint regions 1720, 1666, 1611, 1529 cm(-1) that respectively corresponds to binding in GT, ATGC, C, and AC (A, T, G, and C representing the four nucleotides). Existence of CD signal in the silver plasmon region (350-550 nm) suggests formation of a chiral clustering of nanoparticles. The reciprocal effect on the covalently closed circular (CCC) pUC19 DNA, namely the transition to a relaxed state, can be regarded as a mimicry of the topological enzyme acting on such CCC DNA. PMID- 20352724 TI - Size dependent chaperon properties of gold nanoparticles. AB - Citrate synthase is a heat labile enzyme showing a loss of activity even in response to a modest shift of temperature (35 degrees-45 degrees C). Gold nanoparticle is shown to prevent the thermal aggregation of this enzyme. The chaperon like activity of the nanoparticle diminishes if the particle size is reduced from 40 nm to 20 nm keeping the atomic concentration of gold constant. This implies that the effect is not merely due to enhanced surface area offered by the nano-surfaces. The effect is reversible as the protein separated out from nanoparticles behaves similar to control. The observed coupling between chaperon activity of the nanoparticle and its cluster forming ability is illustrated in terms of a thermal cage model. PMID- 20352725 TI - Surface functionalization of carbon micro coils and their selective immobilization on surface-modified silicon substrates. AB - Surface functionalization of carbon micro coils (CMCs) was performed by acid treatment at different times. Nitric acid oxidation produced CMC with acidic functional groups, although morphology of CMCs was modified after the oxidation. The selective immobilization of as-prepared CMC from an aqueous dispersion was examined on differently surface-modified silicon substrates. It was confirmed that the acid-treated CMC was selectively immobilized on a silicon substrate by chemical bonding with amine-terminated self-assembled monolayers on a silicon substrate, while the pristine CMC was not. PMID- 20352726 TI - Structural, electronic, and magnetic properties of boron nitride nanotubes filled with iron nanowires. AB - Under GGA, the structural, electronic, and magnetic properties of Fe(n) nanowire encapsulated in BNNTs have been investigated systematically using the first principles PAW potential within DFT. We find that the initial shapes (quadratic prismatic Fe wire and cylindrical (8,8) BNNT) are preserved without any visible changes and no one relative rotation is taken place after optimization for the thin nanowires encapsulated inside BNNTs, and the formation processes of such systems are exothermic due to the weaken interactions between them. The magnetic moments analyses show that no magnetization is found on the B and N atoms, but a significant enhancement of the magnetic moments is found for Fe(n) @ (8,8) systems, especially for thin nanowires encapsulated in (8,8) BNNT due to increased ratio of the surface atoms with less coordination number compared to bulk Fe, and very weak influence of outer nanotubes leading to their magnetic moments are similar to those of the freestanding nanowires. Both the total density of states (DOS) and charge density analyses show that the spin polarization and the magnetic moment of Fe(n) @ (8,8) systems come solely from the Fe(n) nanowire, implying the Fe5 @ (8,8) and Fe9 @ (8,8) systems can be applied to the circuits that demand preferential transport of electrons with a specific spin. PMID- 20352727 TI - Layer-by-layer deposition of silver/gold nanoparticles for catalytic reduction of nitroaromatics. AB - A general method has been fabricated to achieve normal as well as inverted core shell architectures of silver/gold through a layer-by-layer deposition technique on a commercial anion exchange resin. Electrostatic field force of the charged resin beads supports immobilization of anionic metal precursors [MX(n)]-, in turn deposition of silver/gold nanoparticles onto the solid resin matrix and reduction of 2-nitrobenzoic acid to obtain the corresponding amines through effective catalysis. The shell thickness has been tailored made by exploiting a new method of cyclic and repetitive deposition of the desired metal precursors. Thermodynamic parameters for the reduction reaction have been presented. Kinetic study reveals a comparative account of rates between the mono- and bi-metallic nanoparticles where silver stands to be a better catalyst for the reduction of nitroaromatics. PMID- 20352728 TI - Construction of uric acid biosensor based on biomimetic titanate nanotubes. AB - A uric acid biosensor has been fabricated through the immobilization of uricase on glassy carbon electrode modified by biomimetic titanate nanotubes of high specific surface area synthesized by hydrothermal decomposition. The so constructed biosensor presents a high affinity to uric acid with a small apparent Michaelis-Menten constant of only 0.66 mM. The biosensor exhibits fairly good electrochemical properties such as the high sensitivity of 184.3 microAcm(-2)mM( 1), the fast response of less than 2 s, as well as the wide linear range from 1 microM to 5 mM. These performances indicate that titanate nanotubes could provide a favorable microenvironment for uricase immobilization, stabilize its biological activity, and function as an efficient electron conducting tunnel to facilitate the electron transfer. This suggests an important potential of titanate nanotubes in uric acid biosensors. PMID- 20352729 TI - Large scale NaLaMo2O8 nanospindles: synthesis, characterization, and luminescence properties. AB - Large scale tetragonal NaLaMo2O8 nanocrystallines with spindle morphology have been prepared through a facile method by low-temperature hydrothermal treatment of Na2MoO4, LaCl3, and EDTA in an ethanolamine/water mixed solution. The products were characterized by X-ray powder diffraction, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, and photoluminescence spectroscopy. Results indicate that High-quality, and uniform nanospindles with a mean length of 260 nm and a mean width of 100 nm can be easily obtained. Furthermore, EDTA and EA (ethanolamine) were found to have great influence on the formation of NaLaMo2O8 spindlelike nanostructures. The room temperature PL spectrum of the products shows a relatively strong emission peak at 365 nm. PMID- 20352730 TI - Facile synthesis of boron nitride nanotubes and improved electrical conductivity. AB - A layer of catalyst film on substrate is usually required during the vapor-liquid solid (VLS) growth of one-dimensional (1D) nanomaterials. In this work, however, a novel approach for synthesizing high-purity bamboo-like boron nitride (BN) nanotubes directly on commercial stainless steel foils was demonstrated. Synthesis was realized by heating boron and zinc oxide (ZnO) powders at 1200 degrees C under a mixture gas flow of nitrogen and hydrogen. The stainless steel foils played an additional role of catalyst besides the substrate during the VLS growth of the nanotubes. In addition, the electrical conductivity of the BN nanotubes was efficiently improved in a simple way by coating with Au and Pd nanoparticles. The decorated BN nanotubes may find potential applications in catalysts, sensors and nanoelectronics. PMID- 20352731 TI - Tumor targeting of protein through poly(ethylene glycol) conjugation with metal coordination. AB - The objective of this study is to introduce a new and simple conjugation method of protein with poly(ethylene glycol) (PEG) based on metal coordination. A chelating residue N,N-bis(carboxymethyl)-L-lysine (NTA) was chemically introduced into one terminal of PEG with another terminal of methoxy group (MeO-PEG). Cu2+ or Zn2+ ions were chelated into the NTA residue of MeO-PEG-NTA prepared. Chromatographic experiments revealed that transferrin (Tf) was conjugated to the MeO-PEG-NTA based on Cu2+ ions coordination. The amount of PEG conjugated increased with an increase in that added. Fluorescently labeled Tf was conjugated by the MeO-PEG-NTA with Cu2+ or Zn2+ coordination and injected intravenously into tumor-bearing mice. The Tf conjugated with the MeO-PEG-NTA based on Cu2+ coordination was accumulated in the tumor site to a significantly great extent compared with the free Tf and Tf conjugated with the Zn2+ coordinated MeO-PEG NTA. A body distribution assay with radiolabeled Tf demonstrated that PEG conjugation with Cu2+ coordination enabled Tf to prolong the blood circulation and enhance the tumor accumulation. When interferon (IFN) was conjugated with the Cu(2+)-coordinated MeO-PEG-NTA and subcutaneously injected into tumor-bearing mice, the in vivo tumor growth was significantly suppressed compared with the injection of free IFN and IFN conjugated by Zn(2+)-coordinated MeO-PEG-NTA. It is concluded that the Cu(2+)-coordinated PEG conjugation can modify the body distribution of protein only by simple mixing in aqueous solution. The PEG conjugation with metal coordination could increase the in vivo half-life period of proteins in the blood, and consequently enhance the accumulation amount at the tumor site. PMID- 20352732 TI - "Spontaneous electrolysis" and simultaneously assembly hierarchy nanostructures of copper tetracyanoquinodimethane. AB - A simple method was developed to generate nanolamellas of CuTCNQ based on the principle of "spontaneous electrolysis". The nanolamellas were identified to belong to phase I of CuTCNQ. Intermediate products before nanolamellas were monitored with this method and beautiful artificial flowers were assembled based on the "spontaneous electrolysis." Moreover, CuTCNQ nanocrystal arrays could be grown on TCNQ single crystal surface homogeneously, which suggested a new method to assembly nanomaterials on crystal surface. PMID- 20352733 TI - Enhanced density control of Al:ZnO nanowires via one-by-one coupling of nanowires and pyramids. AB - Al doped ZnO nanowire arrays with controlled growth densities were fabricated on silicon without using catalysts via sputtering followed by thermal chemical vapor deposition (CVD). Scanning electron microscopy and high-resolution transmission electron microscopy results show that the Al:ZnO single-crystalline nanowires synthesized by CVD prefer growing epitaxially on the tips of the ZnO pyramids pre synthesized by sputtering with the c-axis perpendicular to the substrate. Consequently, the densities of the as-grown Al:ZnO nanowires were controllable by changing the particle densities of the pre-grown ZnO seed layers. The Al concentration of the Al:ZnO nanowires were measured to be around 2.63 at.% by electron energy loss spectrum. Field-emission measurements show the turn-on fields of the Al:ZnO nanowire arrays with controllable area densities are tunable. Room-temperature cathodoluminescence spectra of the Al:ZnO nanowires show relatively strong and sharp ultraviolet emissions centered at 383 nm and broad green emissions at around 497 nm. This work provides a simple method to control the field emission and luminescence densities of Al doped ZnO nanowire arrays, which also shows good potential for developing nano-pixel optical devices. PMID- 20352734 TI - Controllable synthesis of alpha-MnO2 nanostructures and phase transformation to beta-MnO2 microcrystals by hydrothermal crystallization. AB - Single-crystalline alpha-MnO2 nanowires and beta-MnO2 microcrystals have been controllably synthesized by a common hydrothermal method based on the redox reaction between MnO4- and Cr3+. The products were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and high-resolution transmission electron microscopy (HRTEM). The effects of various experimental conditions on the morphologies and crystalline structures of the final products were investigated. It was found that alpha-MnO2 nanowires were converted to beta-MnO2 microcrystals by prolonging the hydrothermal treatment under a dissolution-recrystallization process. Higher hydrothermal temperature and lower pH value were beneficial for the phase transformation from alpha-MnO2 to beta-MnO2. PMID- 20352735 TI - Vice to virtue: intracellular biogenic nanoparticles for the generation of carbon supported catalysts. AB - Intracellular biogenic nanoparticles are considered disadvantageous as the separation of the nanoparticles from the biomass becomes intricate. However realizing the importance of carbon supported catalyst for many important organic reactions we envisaged these nanoparticles as a source for carbon supported catalyst. Herein we demonstrate the heat treatment of intracellular biogenic nanoparticles under inert atmosphere as an efficient method for the preparation of carbon supported metal oxide catalysts. Aspergillus ochraceus, a fungus isolated from foundries, on incubation with K2TiF6 led to the synthesis of intracellular titanium oxide nanoparticles. The nanoparticles embedded biomass upon heat treatment at 600 degrees C in a nitrogen environment gave titanium oxide nanoparticles implanted in a carbonaceous matrix. The material thus formed was characterized using FTIR spectroscopy, Raman spectroscopy, HRTEM and X-ray diffraction. Appreciable benzaldehyde selectivity was observed when styrene oxidation was carried out over such immobilized catalysts. The conversion rate was determined to be 76% and the benzaldehyde selectivity was greater than 80%. PMID- 20352736 TI - Microstructural properties at the interfaces of ZnO nanorods and ZnO homo-buffer layers. AB - Uniformly and vertically well-aligned ZnO nanorods were fabricated in-situ and ex situ on ZnO films using a catalyst-free metal-organic chemical vapor process. Microstructural properties of the initial growth of ZnO nanorods on ZnO films with different surface roughnesses were investigated. We observed that the ZnO nanorods grown on ZnO films with surface roughness of less than 1.0 nm were well aligned along the c-axis and in the ab-plane. When the nanorods grew on ZnO films with a large surface roughness, they had three different growth directions of 28 degrees, 62 degrees, and 90 degrees to the film surface. The slant angle of 62 degrees corresponds to the angle between the ZnO(001) and (101) planes. The initial growth direction difference caused structural disorder at the interface of the ZnO nanorod and film, and prevented epitaxial growth and the alignment of the nanorods. PMID- 20352737 TI - A facile route of gold nanoparticle synthesis and surface modification using amino-terminated poly(ethylene oxide)-poly(propylene oxide) block copolymers. AB - We report here a facile synthetic method and surface modification of gold nanoparticles using amino-terminated poly(ethylene oxide)-poly(propylene oxide) block copolymers (CH3-[OCH2CH2]x-[OCH2CH(CH3)]y-NH2; EO(x)PO(y)NH2) (SURFONAMINE) as media, reducing agents, stabilizing agents and surface-modifying agents. Gold nanoparticles were synthesized through autoreduction of hydrogen tetrachloroaureate(III) hydrate (HAuCl4 x 3H2O) by SURFONAMINE as media and reducing agents at ambient conditions (approximately 25 degrees C). The AuCl4- reduction and gold nanoparticle formation were promoted by SURFONAMINE with longer PEO segment and heating. The enhanced-activity of SURFONAMINE for AuCl4- reduction contributed to particle growth due to the AuCl4- reduction by SURFONAMINE anchored on gold nanoparticles. Furthermore, amphiphilic property of the gold nanoparticle surface was controlled in terms of EO/PO unit ratio of SURFONAMINE. For example, gold nanoparticles synthesized in SURFONAMINE L-207 (EO33PO10NH2) homogeneously mixed with water but not with cyclohexane. On the other hand, gold nanoparticles synthesized in SURFONAMINE B-200 (EO6PO29NH2) were miscible with cylcohexane while immiscible with water. PMID- 20352738 TI - Preparation and characterization of a new hydrophilic C60 derivative (OH)16C60CHCOOH. AB - C60 and its derivatives are very important nanomaterials in biological and materials science. Unfortunately, due to the high hydrophobicity of the C60 cage, most of these materials are insoluble in water and their usages are quitely restricted. Here we reported the preparation and characterization of (OH)16C60CHCOOH, a new multihydroxylated methanofullerene carboxylic acid (MMFCA) derivative with high aqueous solubility. The elementary analysis, FT-IR and 1HNMR confirmed the structure of this material. Like other C60 and its derivatives, this new derivative also contains the free radical scavenging ability, measured by electron spin resonance (ESR) test. On the other hand, the MTT assay showed it had low cytotoxicity. Therefore, this new MMFCA derivative might be a potential vehicle for the introduction of hydrophobic C60 derivatives into water or a hydrophilic environment. PMID- 20352739 TI - Fabrication of one dimensional polyaniline nanofibers by UV-assisted polymerization in the aqueous phase. AB - At the room temperature, a novel and environmental friendly approach for synthesizing polyaniline (PANI) nanofibers on a large scale is presented firstly in the aqueous phase by ultraviolet (UV)-assisted polymerization using cetyltrimethylammonium bromide (CTAB) as the "soft-template." It is obvious that the polymerization process can be accelerated under the illumination of UV light and the preliminary mechanism has been pointed out. Furthermore, it also can be noted that the lower concentrations of CTAB and HCl are helpful for the fabrication of smooth and uniform PANI nanofibers. As observed with FE-SEM and TEM, the as-synthesized PANI nanostructures under the appropriate conditions are composed of uniform nanofibers with the average diameter of about 100 nm and the length of several micrometers. Subsequently, the synthesized PANI nanostructures are characterized with UV-vis, FT-IR, XRD spectra, and the typical physical and chemical properties of PANI are displayed. In addition, the conductivity of the synthesized PANI nanofibers was also measured with the four probe method and the excellent conductivity was presented. In summary, the procedure presented here only involving exposure of an acidic aqueous solution of aniline to UV light illumination is so simple and the needed equipment is so low cost, from the viewpoint of technological applications, that the large-scale UV-assisted polymerization of PANI nanofibers from the monomer solution is feasible and promising. PMID- 20352740 TI - Carbon nanotube mat as mediator-less glucose sensor electrode. AB - In this paper, the direct electron transfer of glucose oxidase (GOx) on carbon nanotube (CNT) mat electrode is demonstrated. Because of the electrical conductivity and mechanical strength of CNT mat, it can be used as an electrode as well as a catalyst support. Therefore, the preparation process for the CNT mat based sensor electrode is simpler than that of the conventional CNT dispersed sensor electrodes. GOx was covalently immobilized on the oxidized CNT mat, which is connected to a wire by using silver paste and epoxy glue. Attenuated Total Reflectance Fourier Transform-Infrared (ATR-FTIR) result shows transmittance peaks at 1637 cm(-1) and 1525 cm(-1) which are corresponding to the band I and II of amide. Cyclic voltammetric shows a pair of well-defined redox peaks with the average formal potential of -0.425 V (vs. Ag/AgCl reference electrode) in the phosphate buffered saline solution (1 x PBS, pH 7.4). Calculated electron transfer rate constant and the surface density of GOx were 1.71 s(-1) and (3.27 +/- 0.20) x 10(-13) mol/cm2, respectively. Cyclic voltammograms of GOx-CNT mat in glucose solution show that the immobilized GOx retains its catalytic activity to glucose. The amperometric sensor response showed a linear dependence on the glucose concentration in the range of 0.2 mM to 2.18 mM with a detection sensitivity of 4.05 microA mM(-1) cm(-2). The Michaelis-Menten constant of the immobilized GOx was calculated to be 2.18 mM. PMID- 20352741 TI - Interface enhancement of glass fiber/vinyl ester composites with carbon nanotubes synthesized from ethanol flames. AB - Multi-walled carbon nanotubes synthesized from ethanol flames (F-MWCNTs) and nanotubes functionalized by n-hexadecylamine (H-MWCNTs) were applied to the preparation of glass fiber/vinyl ester composites by overcoating the original glass fiber. Scanning electron microscopy of the composites containing multi walled carbon nanotubes (MWCNTs) showed better bonding between the glass fiber and the resin matrix which may be attributed to the existence of a flexible interphase introduced by the nanotubes. It was found that the bonding in the composites treated with H-MWCNTs was much stronger. Moreover, the dynamic mechanical properties and impact strengths of the resulting composites were investigated. The results revealed that treating glass fiber with MWCNTs effectively improved the mechanical properties of the composite materials. Furthermore, the dynamic properties showed that H-MWCNTs have become integral parts of the crosslinked polymer structure, rather than acting as separate fillers. PMID- 20352742 TI - Simultaneous enhancement of tensile/compressive strength and ductility of magnesium alloy AZ31 using carbon nanotubes. AB - AZ31 nanocomposite containing carbon nanotube (CNT) reinforcement was fabricated using solidification processing followed by hot extrusion. The CNT reinforcement was integrated with AZ31 using an Al foil method. The AZ31 nanocomposite exhibited slightly smaller grain and intermetallic particle sizes than monolithic AZ31, reasonable CNT distribution, dominant (10 - 11) texture in the transverse and longitudinal directions unlike monolithic AZ31, and 48% higher hardness than monolithic AZ31. Compared to monolithic AZ31, the AZ31 nanocomposite exhibited higher 0.2%TYS, UTS, tensile failure strain and tensile work of fracture (WOF) (+10%, +17%, +68% and +92%, respectively). Similarly, compared to monolithic AZ31, the AZ31 nanocomposite exhibited higher 0.2%CYS, UCS, average compressive failure strain and compressive WOF (+58%, +3%, +5% and +17%, respectively). Inclusive of crystallographic texture changes, the effect of CNT integration on the enhancement of tensile and compressive properties of AZ31 is investigated in this paper. PMID- 20352743 TI - Biodegradable poly(butylene succinate)/multi-walled carbon nanotubes nanocomposite at low carbon nanotubes loading: morphology, crystallization and mechanical property. AB - Biodegradable nanocomposite based on poly(butylene succinate) (PBSU) and multi walled carbon nanotubes (MWNTs) was prepared by solution blending method at 1 wt% MWNTs loading. Scanning electron microscopic observation illustrates a homogeneous distribution of MWNTs in the PBSU matrix. Differential scanning calorimetry, optical microscopy, and wide angle X-ray diffraction were used to study the nonisothermal crystallization, isothermal crystallization kinetics, spherulitic morphology, and crystal structure of neat PBSU and its nanocomposite. The presence of MWNTs enhances the crystallization of PBSU in the nanocomposite due to the heterogeneous nucleation effect while the crystallization mechanism and crystal structure of PBSU do not change. Moreover, the incorporation of a small quantity of MWNTs has improved significantly the mechanical property of PBSU in the nanocomposite compared with that of neat PBSU. PMID- 20352744 TI - Controlling the morphology of nanostructured barium titanate by hydrothermal method. AB - Nanostructured BaTiO3 particles have been synthesized by hydrothermal method using a layered titania nanosheet as Ti precursor. The influence of processing parameters on the formation of BaTiO3 was investigated in this paper. The BaTiO3 particles show different shapes including irregular, sphere-like and plate-like structures by treating the titania nanosheet in different hydrothermal conditions. The dissolution-recrystallization and in situ topotactic transformation mechanisms are suggested based on observations of the factors that influence BaTiO3 formation, such as Ba(OH)2 concentration, the solvent of ethanol, and reaction temperature. PMID- 20352745 TI - Fast preparation of LiFePO4 nanoparticles for lithium batteries by microwave assisted hydrothermal method. AB - Nanomaterial for lithium batteries can decrease mechanical strain upon lithium intercalation/ deintercalation from lattice, and lead to high rate capability. The currently available microwave technology permits the development and implantation of a temperature-controlled microwave-assisted hydrothermal synthesis (TCMH) of nano-sized cathode material for lithium batteries. Unlike in previous reported traditional hydrothermal synthesis of cathode material LiFePO4, the pure phase of LiFePO4 can be simply and rapidly synthesized for 5 minutes in water under hydrothermal treatment with microwave irradiation. The homogeneous effects induced by microwave irradiation could create a uniform seeding condition. The colloid precursor Li3PO4 plays the key role to be the nucleation center for the new phase while the formation energy for LiFePO4 would be decreased during the following microwave irradiation. The as-prepared pristine LiFePO4 without carbon coating are characterized by X-ray diffraction, Raman, scanning and transmission electron microscopy, and tested as the cathode in lithium batteries. The particle sizes of pristine LiFePO4 are dependent on hydrothermal and microwave-assisted hydrothermal condition and the electrochemical performance are relatively determined. PMID- 20352746 TI - Preparation of hybrid layers consisting of copper nanoparticles and polyimide matrix via polyol in situ reducing process. AB - Hybrid layers consisting of copper nanoparticles and polyimide have been successfully fabricated using copper nitrate as the copper precursor and pyromellitic dianhydride/oxydianiline-(PMDA/ODA-) based polyimide films as the substrate. The fabrication method relies on the potassium hydroxide-induced chemical modification of the polyimide surface to introduce carboxylic acid groups, the incorporation of copper ions through subsequent ion exchange reaction, and followed by the polyol in situ reduction of copper ions contained polyimide layers in ethylene glycol solution at 197 degrees C. The amount of copper ions in the modified layer strongly depended on the ion exchange time. The copper nanoparticles size changed from 3 nm to 27 nm when the reduction time increased from 5 min to 30 min. These experiments provided an efficient route for copper metallization of polyimide substrate. The detailed reaction progress and resulted films were characterized by Attenuated total reflection-Fourier transform infrared, X-ray photoelectron spectroscopy, inductively coupled plasma atomic emission spectrometer, X-ray diffraction, transmission and scanning electron microscope. PMID- 20352747 TI - Low-temperature growth and dye-sensitized solar cells applications of flower shaped ZnO hexagonal nanorods. AB - Flower-shaped ZnO structures composed of hexagonal nanorods were grown in a large quantity via simple aqueous solution process by using zinc nitrate as a source of zinc ions at low-temperature of approximately 85 degrees C. The as-grown flower shaped ZnO structures composed of hexagonal nanorods were characterized in terms of their structural, optical and photovoltaic properties by using X-ray diffraction pattern (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) pattern, FTIR, UV-Vis and Raman-scattering spectroscopy. The detailed structural investigations confirmed that the as-synthesized products are well crystalline and possessing wurtzite hexagonal phase. For the application point of view, the as-grown flower-shaped ZnO structures composed of hexagonal nanorods were used as photo-anode materials to fabricate the dye sensitized solar cells (DSSCs). An overall light to electricity conversion efficiency of 1.1% with a short-circuit current of 4.34 mA/cm2, open-circuit voltage of 0.554 V and fill factor of 0.45, were achieved for the fabricated solar cell based on flower shaped ZnO structures composed of hexagonal nanorods. PMID- 20352748 TI - Control the diameters of mesoporous silica nanotubes by varying stirring time. AB - A chiral cationic gelator derived from L-alanine was synthesized. Sol-gel transcriptions were carried out to control mesoporous silica nanostructures using the organic self-assemblies of this gelator as templates. It was found that the morphologies of the obtained mesoporous silicas were sensitive to stirring time. With increasing the stirring time, the morphologies of mesoporous silicas changed from nanotubes constructed by double twisted nanoribbons to those constructed by single-strip coiled nanoribbons. The diameters of the nanotubes increased from 80 to 400 nm. This result indicated that the formation of the nanotubes following a dynamic templating process. For a better understanding the pore architectures, the TEM images of the mesoporous silicas were simulated using the 3D studio MAX software. PMID- 20352749 TI - Preparation of Mn, Ni, Co ferrite highly porous silica nanocomposite aerogels by an urea-assisted sol-gel procedure. AB - The preparation of highly porous MnFe2O4-SiO2 and NiFe2O4-SiO2 nanocomposite aerogels with high purity and homogeneity was successfully achieved by a sol-gel procedure involving urea-assisted co-gelation of the precursor phases firstly applied for the synthesis of CoFe2O4-SiO2. This method allows fast gelation, giving rise to aerogels with 97% porosity. The structural, morphological and textural characterization as a function of thermal treatments was carried out by a multitechnique approach confirming that, as in the case of CoFe2O4-SiO2, the formation of single nanocrystals of manganese ferrite and nickel ferrite with spinel structure occurs after heating at 750 degrees C and is complete at 900 degrees C when the high porosity typical of aerogels is still retained. Thermogravimetric analysis (TG), differential thermal analysis (DTA), N2 physisorption at 77 K, powder X-ray diffraction (XRD), and transmission electron microscopy (TEM) indicate that the compositional homogeneity, crystallite size, thermal stability, and porosity are controlled by the sol-gel parameters of the preparation. PMID- 20352750 TI - Organic-crystal light-emitting field-effect transistors driven by square-wave gate voltages. AB - We have improved the operation method of organic light-emitting field-effect transistors by applying a square wave to the gate electrode. A thiophene/phenylene co-oligomer crystal was used as the organic layer. Compared with the sinusoidal wave gate bias application, the square-wave bias produces the emission intensity ten times as large as that of the former. The effective emissions take place through electrons injection from the source contact when the gate bias traverses 0 V so as to be positive. When asymmetric electrodes were used for the source and drain contacts, the resulting emission exhibited the narrowed spectral line at 491.5 nm with its FWHM approximately 1.1 nm. The line narrowing is expected to be a consequence of the emission intensity increment caused by the enhanced electrons injection from the Ag source contact. The location of the emission line is closely related to those of the multimodes due to the laser oscillation by cavity resonance. PMID- 20352751 TI - Biomolecule-directed assembly of binary gold and titanium dioxide nanoparticles. AB - We report in this paper a novel strategy for "bottom-up" assembly of two types of metallic and semiconductor nanoparticles. By only using a small biomolecule, coenzyme A, as a "linker" to direct the assembly of metallic gold and semiconductor titanium dioxide nanoparticles, the usual biomolecule-directed system can be greatly simplified. Effects of experimental conditions on the formation of binary nanoparticles are studied. This strategy using single small biomolecule to direct assembly of nanoparticles is proven to be efficient, facile and non-toxic and should be extendable to other building blocks. PMID- 20352752 TI - Three-phase textile nanocomposites: significant improvements in strength, toughness and ductility. AB - It is well established that in-plane tensile properties of unidirectional microfiber-reinforced composites are not significantly influenced by addition of carbon nanotubes to the matrix. This is because the principal effect of the nanotubes is to enhance the matrix dominated (out-of-plane) properties. Here we report that the above situation changes when nanotubes are incorporated into woven-fabric (textile) composites. We report up to 200% increase in strain-to break and 180% increase in toughness under in-plane tensile load with approximately 0.05% weight of nanotube additives. We attribute this effect to the geometrical arrangement of the micro-fibers and the critical role of the pure matrix-block in textile composites. PMID- 20352753 TI - TiO2-based nanopowders and thin films for photocatalytical applications. AB - TiO2-based nanopowders are elaborated by flame spray synthesis, FSS from organic precursors of titanium and chromium with the Cr content changing from 0 to 15 at.%. Well-crystallized nanopowders with high specific surface area SSA reaching 107 m2/g for undoped TiO2 and 177 m2/g for TiO2 + 15 at.% Cr are obtained. Thin films are deposited by rf reactive sputtering from metallic Ti and Ti-Cr targets in Ar + O2 flow controlled atmosphere. The adjustable area of Cr/Ti allows to obtain up to 16 at.% Cr in TiO2 thin films. X-ray diffraction, transmission electron spectroscopy, TEM, atomic force microscopy, AFM and optical spectrophotometry over the ultraviolet UV and visible VIS range of the light spectrum have been performed in order to characterize the nanomaterials. The particle size of nanopowders is within the range of 5-42 nm. Anatase is the predominating polymorphic form while the amount of rutile increases with Cr content to reach of about 25 wt.% at 15 at.% Cr. The post-deposition annealing of thin films in air at temperatures from 770 K to 1280 K modifies the phase composition, leads to irreversible transformation from anatase to rutile and affects the surface roughness. Structural and optical properties of TiO2-based nanopowders and thin films are compared. The effect of grain size and the level of chromium doping on the band gap E(g) is discussed. Photocatalytic activity of the nanopowders is tested for degradation of methylene blue, MB. PMID- 20352754 TI - Nanogenerators based on ZnO or TiO2 oxides. AB - Recently, an approach for converting nanoscale mechanical energy into electrical energy has been suggested by using piezoelectric zinc oxide (ZnO) nanowire arrays. Such devices have been shown to convert ultrasonic energy into electric energy by a deflection of the nanowires via a corrugated electrode operated up and down by the ultrasound. A typical approximately 1 pW output power for a device of a approximately 1 mm2 area and a density of approximately 10(7)/mm2 nanowires can be obtained. In order to reach the approximately 10 nW power needed to operate a nanodevice, nanogenerators of this kind need to be optimized. With the aim of fabricating low cost to efficiency ratio nanogenerators, we have considered ZnO films grown by an electrochemical technique, based on the direct precipitation of Zn hydroxide on a conducting ITO/glass substrate and subsequent heat treatment, and TiO2 films deposited from a colloidal suspension of anatase/rutile commercial powders. These methods allowed us to obtain disordered but quite uniform arrays distributed on the surface of the substrate. Preliminary results on the electrical properties are presented. Under input mechanical strain we find output powers of approximately 10(-9)/cm2 W, which are comparable to those obtained with the ZnO nanoarrays. Possible interpretations of results in terms of piezoelectricity (ZnO) and incipient ferroelectricity (TiO2) are presented and improvements of the devices are discussed. PMID- 20352755 TI - Effect of the growth conditions on the optical and mechanical properties of TiO2 and Al2O3 films. AB - The mechanical and optical properties of TiO2 and Al2O3 films deposited by DC reactive magnetron sputtering were analysed as a function of the deposition conditions. Two different sputtering powers and three different voltages targets which influence the pressure and the deposition rate were studied. The voltage corresponds to two different percentages of the turn down set point of the hysteresis curve and fully poisoned condition. As their optical application is the main functionality of these coatings, the transparency and the refractive index were investigated. However, the mechanical properties are the key factors for determining the performance of these systems in use. For this, the wear resistance of these coatings was studied through the analysis of the evolution of the friction coefficient with time and the analysis of the wear track. The corrosion resistance has been also analysed through electrochemical studies. The results reveal that there is a clear influence of the studied deposition conditions on the mechanical and optical properties of these films. However, while general conclusions could be drawn for Al2O3 films, for TiO2 films the tendency is not so clear and further work needs to be performed. PMID- 20352756 TI - Photoelectrochemical properties of N/C-codoped TiO2 film electrodes prepared by reactive DC magnetron sputtering. AB - This paper aims to characterize the photoelectrochemical properties of the visible-light enabling titanium dioxide (TiO2) film electrodes prepared by codoping nitrogen (N) and a presputtered carbon film (C-film) onto indium tin oxide (ITO) glass substrates using a direct current (DC) magnetron sputtering technique. To improve its photoelectrochemical properties, different amount of C doping sources, 2 h and 4 h C-film, are chose to prepare the N/C-codoped TiO2 film electrodes. Under visible-light (420 < lambda < 610 nm) illumination, a remarkable photocurrent density of 22 microA/cm2 is obtained for the N/C-TiO2 film electrode prepared with a 4 h C-film (NC(4)-T) at an applied potential of +1.2 V versus SCE. Under ultraviolet (lambda approximately 365 nm) illumination, the NC(4)-T film electrode also exhibits the highest photocurrent density of 0.23 mA/cm2 among all samples tested. A more negative flat band potential of NC(4)-T film electrode is attributed to the synergistic effect of N/C codoping. The XRD spectrum of the NC(4)-T film electrode shows mainly the well-crystallized anatase TiO2 phase and an extremely intense (211) plane. Thus, photoelectrochemical activity of the NC(4)-T film electrode can be ascribed to the well-crystallized columnar crystals with pores at its grain boundary, open surface morphology, which are revealed by SEM and TEM images, and a more negative flat band potential. The visible-light induced activity is mostly enhanced as a result of the synergistic effects of N/C-codoping into the TiO2 crystals. A potential application to photocatalytic splitting of water for hydrogen evolution using solar light is practically possible. PMID- 20352757 TI - Biological properties of different type carbon particles in vitro study on primary culture of endothelial cells. AB - Carbon powders have extended surface of carbon layers, which is of significant biomedical importance since the powders are employed to cover implants material. Carbon Powder Particles are produced by different methods: by a detonation method, by RF PACVD (Radio Frequency Plasma Activated Chemical Vapour Deposition) or MW/RF PCVD (Microwave/Radio Frequency Plasma Activated Chemical Vapour Deposition) and others. Our previous data showed that Carbon Powder Particles may act as antioxidant and/or anti-inflammatory factor. However the mechanism of such behavior has been not fully understood. The aim of the work was tested influence carbon powders manufactured by Radio Frequency Plasma Activated Chemical Vapour Deposition RFPACVD method and detonation method on selected parameters of human endothelial cells, which play a crucial role in the regulation of the circulation and vascular wall homeostasis. Graphite powder was used as a control substance. Endothelial cells are actively involved in a wide variety of processes e.g., inflammatory responses to a different type of stimuli (ILs, TNF-alpha) or regulating vasomotor tone via production of vasorelaxants and vasocontrictors. Biological activation is dependent on the type and quantity of chemical bonds on the surface of the powders. The effect of powders on the proliferation of HUVECs (Human Umbilical Vein Endothelial Cells) was determined by MTT (3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay. We found decreased cell proliferation after 72 h treatment with graphite as well as Carbon Powder Particles. PMID- 20352758 TI - N-doped photocatalytic titania thin films on active polymer substrates. AB - Active polymer substrates have found their way in the semiconductor industry as a base layer for flexible electronics, as well as in sensor and actuator applications. The optimum performance of these systems may be affected by dirt adsorbed on its surface, which can also originate mechanisms for the degradation of the polymer. Titanium dioxide (titania) semiconductor photocatalytic thin films have been deposited by unbalanced reactive magnetron sputtering on one of the most applied and investigated electroactive polymer: poly(vinilidene fluoride), PVDF. In order to increase the photocatalytic efficiency of the titania coatings, a reduction of the semiconductor band-gap has been attempted by using a nitrogen doping. Rutherford Backscattering Spectroscopy was used in order to assess the composition of the titania thin films, whereas Heavy Ion Elastic Recoil Detection Analysis provided the evaluation of the doping level of nitrogen. X-ray Photoelectron Spectroscopy provided valuable information about the cation-anion binding within the semiconductor lattice. The photocatalytic performance of the titania films have been characterized by decomposing an organic dye illuminated with combined UV/visible light. PMID- 20352759 TI - Thin film nano solar cells--from device optimization to upscaling. AB - Stainless steel based dye solar cells have been upscaled from small, laboratory size test cells of 0.32 cm2 active area to 6 cm x 6 cm "mini-modules" with active areas ca. 15 cm2. Stainless steel works as the photoelectrode substrate whilst the counter electrode is prepared on indium-doped tin oxide coated polyethyleneterephtalate or polyethylenenaphtalate plastic foil (fluorine-doped tin oxide coated glass as a reference). Additional current collector structures were deposited on the counter electrode substrate with inkjet-printing of silver nanoparticle ink in order to reduce the lateral resistance of the plastic foil. Flexible substrates enable roll-to-roll type industrial manufacturing of the cells and the steel's superior conductivity compared to the typical substrate materials such as glass and plastic makes it possible to prepare even substantially larger modules. The best efficiencies obtained this far with the "mini-module" using a stainless steel photoelectrode are 2.5% with a platinum sputtered indium-doped tin oxide coated polyethyleneterephtalate counter electrode and 3.4% with a thermally platinized fluorine-doped tin oxide coated glass counter electrode. These efficiencies are on the same level than those measured with small cells prepared with similar methods and materials (3.4%-4.7%, depending on configuration, which are amongst the highest reported for this kind of a dye solar cell). Replacing expensive conducting glass with steel and plastic foils as the substrate materials leads also to economical savings in the cell production. PMID- 20352760 TI - Investigation of fine nanoparticles syngas catalyst (POM) considering their various morphology. AB - Ni/SiO2 fine nanoparticles were prepared by coprecipitation method using various nonionic surfactants as templates with Tylose as a binder dispersant. Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD) have been used to study the templates influence on the morphology of the produced samples. Although the phase structure remained as a tetrahedron amorphous cristobalite-sin-SiO2 (101,100), rhombohedron and cubic NiO, but samples with different morphology (homogeneous nano spherical, nano rose flower and nano cubic shapes) have been achieved. These fine nanoparticles as syngas catalysts in Partial Oxidation of Methane to Hydrogen and Carbon Monoxide (POM) have been studied. Because of high Hydrogen production, it is a candidate to be a green fuel. A fixed-bed reactor at P = 1 atm, T = 800 degrees C, H2/CO = 1.8, GHSV (CH4) = 6000/hr and BET = 25, 63.5 and 87.1 m2/gr have been used as POM catalyst. From other hand these fine compounds could be converted to metallic nanotube (nanofiber) at above 850 degrees C and also bamboo shape tip mode carbon nanotube by thermal chemical vapor deposition at 800 degrees C. Transmission Electron Microscopy confirmed the metallic nanotube or single nano crystal growth. The Raman spectroscopy of all samples has been studied to confirm the different formation of Ni-Si. Choosing different templates for production of these nanoparticles could create width range of medical and industrial applications. PMID- 20352761 TI - Self-assembly of nanohills in Si1-xGe(x)/Si hetero-epitaxial structure due to Ge redistribution induced by laser radiation. AB - The study is focused on formation and optical properties of nanostructures induced by laser radiation on the surface of Si1-xGe(x)/Si hetero-structures. Formation of self-assembling nanohills induced by irradiation of nanosecond Nd:YAG laser pulses on the Si0.7Ge0.3/Si hetero-epitaxial structures is reported. The atomic force microscope study of the irradiated surface morphology has shown a start of nanohills formation after laser irradiation of the intensity I = 7.0 MW/cm2. The huge "blue shift" of photoluminescence spectra with maximum intensity in region of 700-800 nm (1.76-1.54 eV) is explained by the quantum confinement effect in the nanohills. The maximum of this photoluminescence band slightly shifts to shorter wavelengths with the increase of the intensity of laser pulses used for sample treatment. Appearance of the 300 cm(-1) Ge-Ge vibration band in Raman scattering spectra for sample irradiated with I = 20.0 MW/cm2 is explained by Ge phase formation. Formation of the Ge-rich phase is explained by localization of Ge atoms drifting toward the irradiated surface under the thermal gradient due to strong absorption of laser radiation. Ellipsometric data confirm appearance of Ge-rich phase precipitates amounting to 7.1%, 6.4% of the total Ge content induced by laser radiation of intensities I1 = 20.0 MW/cm2, I2 = 7.0 MW/cm2 respectively. PMID- 20352762 TI - Enhanced optical properties of TiO2 nanoceramic films by oxygen atmosphere. AB - TiO2 nanoceramic films were deposited on glasses by rf magnetron sputtering and corresponded to nanocrystalline anatase. The porosity and surface roughness decreased with the oxygen pressure. The optical transmission of TiO2 nanoceramic films obviously increased with the decrease of film thickness or the increase of oxygen pressure, especially in the visible region. Moire deflectometry was used to measure the nonlinear refractive indices of TiO2 films deposited in a mixed Ar O2 atmosphere. The nonlinear refractive index was measured to be of the order of 10(-8) cm2 W(-1) and the change in refractive index was of the order of 10(-5). As the oxygen pressure increased, the transparent TiO2 film exhibited a high linear refractive index, a low stress and a low stress-optical coefficient. PMID- 20352763 TI - Influence of the cluster orientation on the epitaxy: deposition of Co nanoclusters on Cu(001) surfaces. AB - Deposition at low energy of 147-atom icosahedral Co nanoclusters on Cu(001) substrates is studied by molecular-dynamics simulations. Atomic interactions were mimicked by a many-body potential based on the tight-binding second-moment approximation. Clusters were rotated by using the two first Euler angles, in the so-called "x-convention," and subsequently, they were deposited on the substrate. The dependence of the degree of epitaxy on these angles has been obtained. Epitaxy is also related to the initial number of (001)-oriented atoms, especially for extreme values of this latter quantity. A better epitaxial matching is connected with a larger spreading index. The explanation of the epitaxial behavior of the supported clusters resides mainly in the dynamical interaction between grains during approximately the first 40 ps. Whenever the newly-formed (001)-oriented grain competes against a large number of grains after the collision, a very low epitaxial matching is obtained. PMID- 20352764 TI - Electrical properties and surface morphology of SiO(x)-Pt nano-composite thin films. AB - Recently, ceramic metals (cermets) have been widely investigated for use as embedded resistor materials. In this study, SiO-Pt nano-composite cermets were developed to control the resitivity and temperature coefficients of resistance (TCR) of embedded thin film resistors. The SiO-Pt nano-composite was prepared by the co-sputtering of a SiO(x) target and Pt chips onto glass. The experiments were conducted Pt concentrations in order to find the optimum conditions to achieve a high resistivity and low TCR. The electrical properties of the sputtered SiO-Pt thin films were investigated by probe station and their crystal structures were observed by X-Ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). The surface morphology was observed by field emission scanning electron microscopy (FE-SEM) and high resolution transmission electron microscopy (HR-TEM). It was found that the Pt particles with a size of 3 approximately 5 nm were uniformly dispersed in the SiO matrix. A stable resistivity value of 26000 approximately 57000 microomega x cm and TCR value of 197 approximately -322 ppm/K were obtained at 3.5 approximately 3.7 at.% Pt. PMID- 20352765 TI - Ordered metal nanotube arrays fabricated by PVD. AB - In this work we report a simple method to fabricate ordered arrays of metal nanotubes. This method is based on the deposition of a metal by PVD onto an anodized aluminum oxide (AAO) template. The dimensions of the synthesized nanotubes depend both on the AAO template and on the deposited metal. In fact, it is observed that the aspect ratios of the nanotubes clearly depend significantly on the metal, ranging from 0.6 (Fe) to at least 3 (Zr). PMID- 20352766 TI - Sputter deposition of nanocrystalline beta-SiC films and molecular dynamics simulations of the sputter process. AB - Thin nanocrystalline films of silicon carbide (SiC) have been deposited on Si substrates by rf magnetron sputtering in pure Ar atmosphere. Simultaneously classical molecular dynamics (MD) simulations of sputtering of beta-SiC by Ar atoms were performed using IMD and Materials Explorer software with a combination of the Tersoff and the Ziegler-Biersack-Littmark (ZBL) potential in order to get more insight into the sputter process. In experiments the bias voltage (0 to -40 V) has been varied at constant substrate temperature of 900 degrees C to investigate the influence on the composition, the constitution and the mechanical properties of crystalline beta-SiC films. At second the substrate temperature has been varied between 900 degrees C and 100 degrees C to find the minimum substrate temperature that is needed to get nanocrystalline beta-SiC under the applied sputter conditions (ceramic SiC target, 300 W rf power, 18 cm target-substrate distance, 50 sccm Ar gas flow, 0.26 Pa total gas pressure). The films have been characterized by electron probe micro-analysis (EPMA), X-ray diffraction (XRD), Raman spectroscopy and atomic force microscopy (AFM). Hardness and residual stress have been investigated by nanoindentation and wafer bending. In the MD simulations the sputter yield was determined as a function of the energy of the incident Ar atoms (in the interesting range for sputter deposition, i.e., 50-1000 eV). To our knowledge this is the first time that the sputter yield of a SiC target was determined as a function of the energy of the incident Ar atoms in the low energy range by using MD simulations and compared with experimental results. PMID- 20352767 TI - Bacteria-mediated synthesis of free-standing cobalt oxide rods. AB - We demonstrate the simple room-temperature preparation of rod-type, oxide nanostructures derived from the Bacillus subtilis templates. Specifically, free standing, cobalt oxide rods were produced via the following systematic processes: incubation of the bacteria templates in aqueous cobalt chloride solution, reduction with sodium borohydride (NaBH4), and subsequent oxidation in water at room temperature. We observed that single nanocrystals or small clusters approximately 3 to 5 nm in diameter were uniformly distributed on the as-prepared individual rods. Additionally, thermogravimetric (TG) analysis and field emission electron scanning microscopy (FESEM) observation revealed the important role played by the concentration of the reductant, NaBH4, in anchoring the cobalt oxide nanocrystals on the bacterial cell surface. Our proposed strategy facilitates the economic and easy construction of other oxide nanostructures and assemblies for applications in nanoelectronics, photonics, sensing, catalysis, and energy storages. PMID- 20352768 TI - ZnO nanowire-based UV photodetector. AB - ZnO nanowire-based ultraviolet (UV) photodetector was proposed and fabricated by depositing interdigitated Au film on vertically well aligned ZnO nanowires. It was found that the deposited Au film form good ohmic contact with the underneath ZnO nanowires. Upon UV irradiation, it was found that the detector current was increased by more than 2.5 times. It was also found that the corresponding time constant for turn-on transient was tau(on) = 3.125 ms while that for turn-off transient was tau(off) = 36.92 ms. PMID- 20352769 TI - Fabrication of functionalized nanofiber membranes containing nanoparticles. AB - The present scenario is that neutral or uncharged polymers are electrospun first followed by surface modification to introduce the functional groups onto the nanofibers surface. These groups improve the adhesion between the nanofibers and materials to be coated. The surface modification involves significant steps to get desired functional groups on the nanofibers surface and also time consuming. This paper deals with one step fabrication of nanofibers with hydroxyl functional groups. Nanofibers were fabricated by electrospinning of poly(ethylene terephthalate) (PET) with cellulose acetate (CA) or cellulose (C). Deposition of various metal oxide nanoparticles on these nanofiber surfaces was carried out using liquid phase deposition (LPD) and electrospraying techniques. Distribution of the nanoparticles and aggregation minimization were obtained by optimization of electrospraying technique. The nucleation density and the morphology of coated nanoparticles by LPD technique on PET surface were lower amount, whereas they are higher on PET/CA and PET/C blended surface, due to hydroxyl functional groups on the blended nanofiber surface, which is a novel. This study is helpful to understand about the complimentary information of the process based on the adoption of these two techniques. The characterizations of these nanofibers were carried out by using SEM, contact angle analysis, tensile, porosity measurements, and EDAX analysis. These membranes find potential applications as filter media in protective clothing and air filter applications. PMID- 20352770 TI - Quantum and nanoscale modelling of exciton dynamics in polymeric systems. AB - One of the factors that limit the efficiency of polymer-based optoelectronic devices, such as photovoltaic solar cells and light emitting diodes, is the exciton diffusion within the polymeric network. Due to the amorphous nature the of polymeric materials, the diffusion of excitons is limited by the energetic and spatial disorder in such systems, which is a consequence not only of the chemical structure of the polymer but also from its morphology at nanoscale. To get a deep understanding on how such effects influence exciton dynamics we performed a quantum molecular dynamics simulations to determine the energetic disorder within the polymer system, and Monte Carlo simulations to study exciton diffusion in three-dimensional (3D) polymer networks that present both spatial and energetic disorder at nanometre scale. Our results show clearly that exciton diffusion in poly(p-phenylenevinylene) (PPV) occurs preferentially in the direction parallel to the electrodes surface for a polymer-based optoelectronic devices with the orientation of the conjugated strands similar to those obtained by the spin coating technique and the decay of such excitons occurs preferentially in longer strands which allow us to get insight on exciton behaviour in polymeric systems that are not possible to be obtained directly from the experiments. PMID- 20352771 TI - Characterization of superparamagnetic iron oxide coated with silicone used as contrast agent for magnetic resonance image for the gastrointestinal tract. AB - The present work is a report of the characterization of superparamagnetic iron oxide nanoparticles coated with silicone used as a contrast agent in magnetic resonance imaging of the gastrointestinal tract. The hydrodynamic size of the contrast agent is 281.2 nm, where it was determined by transmission electron microscopy and a Fe3O4 crystalline structure was identified by X-ray diffraction, also confirmed by Mossbauer Spectroscopy. The blocking temperature of 190 K was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above the blocking temperature. Ferromagnetic resonance analysis indicated the superparamagnetic nature of the nanoparticles and a strong temperature dependence of the peak-to-peak linewidth deltaH(pp), giromagnetic factor g, number of spins N(s) and relaxation time T2 were observed. This behavior can be attributed to an increase in the superexchange interaction. PMID- 20352772 TI - Comparison of physicochemical properties of three nanostructure composite TiO2 films and their photocatalytic properties. AB - Three type of photocatalytic composite films, MPC500SGF-MC, ANPSGF-MC and P25SGF MC, have been synthesized by a modified sol-gel method using different particle size of TiO2 nanopowder MPC500, ANP and P25, respectively. Methyl cellulose (MC) was added as a template to the sol for stress reduction which improved not only the amount of crystalline material immobilized on the support, but also the nanosize of the films calcined at 500 degrees C. The physicochemical properties, including surface morphology, crystallinity, crystal size and adhesion on glass substrate, of the three types of films were investigated by SEM, XRD and the scratch test. The photocatalytic activities of the films were compared using methyl orange (MO) as a model organic contaminant in water. The results on photocatalytic degradation of MO showed that the increase in photocatalytic activity for P25SGF-MC, compared with that of MPC500SGF-MC and ANPSGF-MC composite films. The optimum degradation conditions of MO solution are determined. This study proves that particle size of starting TiO2 material is important for the preparation of nanostructured TiO2 composite film with enhanced photocatalytic activity and excellent adhesion on the glass substrate. PMID- 20352773 TI - Mechanism of phase separation generation in Ge-based solar cell tunnel junctions. AB - Enhanced performance, reduced cost and compact dimensions are a prerequisite for novel products in the solar industry. III-V based multi-junction heterostructures are promising devices to give an answer to make a substancial step in the photovoltaic technology. However, such heterostructures need tunnel junctions to connect the different active layers and so ternary alloys are needed to tune the energy gap. In the present contribution, artefacts generated by ternary alloying are investigated by transmission electron microscopy (TEM). Composition modulation in In0.015Ga0.985As/In0.3Ga0.7P/Al0.3Ga0.7As/In0.3Ga0.6Al0.1P/In0.3Al0.7P/In0.015Ga0 985As heterostructures grown on Ge subtrates is observed. This should affect the spectral sensitivity of the active layer. But, as a probably more important consequence, this observed modulation is shown to also generate modulation in the Al0.3Ga0.7As tunnel junction. This behaviour is anomalous in standard AIGaAs thick epilayers grown on GaAs substrates. In the present case, it could strongly affect the carrier transport imposing an important handicap to their potential application within electro-optical components. PMID- 20352774 TI - Spray plasma device, a new method to process nanostructured layers. application to deposit ZnO thin layers. AB - The aim of this paper is to present a new plasma spray device to deposit nanostructured films. In this process, aqueous droplets of a starting material, in this case, a nitrate salt, of small and uniform size produced in an aerosol generator are injected into a low pressure plasma reactor. Droplets are then submitted to the reactivity of plasma and projected against a substrate where they form the final film. The reactor is designed to reduce the turbulence that results in coalescence of the particles and affects the uniformity of the deposited films. The plasma is produced by an inductive RF generator that avoids the contamination of the layers by electrodes. The control of plasma gas composition, i.e., argon and oxygen, permits adjustment of the concentration of reactive species leading to control the stoichiometry of the deposited layers. The ability of this process to produce nano scale zinc oxide films by the use of an aqueous solution containing Zn(NO3)2 is demonstrated. The films obtained under defined experimental conditions are smooth, colorless and transparent. SEM and AFM photographs show the formation of uniform layers with 20 to 60 nm in thickness. XRD patterns of deposited films showed that preferential c-axis orientation of crystallites depends highly on the concentration of Zn(NO3)2 in the starting solution. Willamson-Hall method in accordance with AFM photographs showed that the size of crystallites ranges between 24 and 34 nm. PMID- 20352775 TI - Characterisation and tribological investigation on thermally processed nanostructured Fe-based and Cu-based cermet materials. AB - The feasibility of achieving a nanostructured material after different thermal processing of nanosized powders is presented. The thermal processing was done by either atmospheric plasma spraying, laser sintering, or extrusion followed by hot isostatic pressing. The structural characterisation of such thermally processed nanostructured Fe-based and Cu-based metallic or Al2O3 reinforced cermets, confirmed the retention of a nanostructure after each of these thermal processes. Hardness measurements confirmed an increased hardness as expected in the case that nanostructuring is achieved. The role of grain boundaries and second phase particles on the retention of the nanostructure after thermal processing is discussed. Finally, the possible benefit of nanostructuring on the friction and wear behaviour of materials in sliding tests against corundum in ambient air is reported and discussed. PMID- 20352776 TI - Hydrothermal synthesis, characterization and photocatalytic properties of Cu2PO4OH with hierarchical morphologies. AB - Cu2PO4OH with various hierarchical morphologies were synthesized using a hydrothermal method by simple adjusting the pH value and temperature. The prepared powders were characterized by X-ray diffraction (XRD), Raman spectroscopy, fourier-transform infrared spectroscopy (FT-IR), and UV-Vis diffuse reflectance spectroscopy. It was found that overall morphologies of Cu2PO4OH were varied from micro-rods to walnut-like microspheres as increasing the initial solution pH value and their size of the assembled crystallites was smaller at lower temperature. From the FT-IR and Raman analysis, the incorporation of the hydroxyl ions (OH-) into the crystal structure plays important roles to their crystallization process, and finally affects their morphologies. Moreover, the optical absorption properties of the Cu2PO4OH were strongly related to their morphologies. The photocatalytic activity of Cu2PO4OH with various morphologies was also investigated via the degradation of rhodamine B (RhB) dye solution under visible light irradiation (lambda > 410 nm). The walnut-like microsphere assembled with nanoparticles exhibited higher photocatalytic activity due to the higher optical absorption as well as a higher surface area. PMID- 20352777 TI - Nanostructured protective carbon layer on the jeweller's metallic material--in vitro verification. AB - In this paper the surface condition of jeweller's metallic material covered by nanostructured carbon layer after the in vitro model test was investigated. The phenomenon of body modification has made that the most popular and the most often applied is jewellery made of metals like stainless steel, titanium and its alloys. However these kinds of metals are not safe and can cause health complications. Biocompatible carbon coatings were used in order to exclude the side effects of metallic jewellery use. Body modification trend is popular among youth to a large degree--they who are always looking for the cheap decorations. Taking this fact into consideration the jewellery made of stainless steel, which is used the most often was exposed to modification by carbon coating. Two methods of plasma activated chemical vapour deposition (PA CVD) were used for the carbon coatings production purpose: radio frequency (RF) and microwave/radio frequency (MW/RF). In order to point the best parameters of these coatings manufacture processes, examinations of physiochemical properties and analysis of surface topography (optical microscopy, scanning electron microscopy with X-ray microanalysis) were made. So modified jewellery was investigated in in vitro model as regards resistance to the biological environment and coatings stability as well. The conducted examinations showed that modifications of decorations made of 316L stainless steel by carbon coatings allow for the creation of biocompatible, non-toxic jewellery. Tests showed that human fibroblasts grow and keep vitality in a presence of jewellery covered by carbon coating, whereas die very fast sticking the non-modified surfaces of decorations. The carbon coating constitutes a barrier which isolates jewellery from the surrounding environment and simultaneously contacts with it in a safe way. PMID- 20352778 TI - Preparation of N-doped CaNb2O6 nanoplates with ellipsoid-like morphology and their photocatalytic activities under visible-light irradiation. AB - Nitrogen-doped CaNb2O6 nanoplates with an ellipsoid-like morphology were prepared using the hydrothermal method, followed by heat treatment at various temperatures in an NH3 atmosphere. The prepared powders were characterized using X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. It was found that the nitrogen doping in the CaNb2O6 nanoplates led to the formation of nanoparticles with a size of 10 nm at the surface and the red shift of the light absorption edge into the visible light region. From the electronic band structure calculation using density functional theory (DFT), this was found to be caused by the broadening of the top of the valence band due to the hybridization of the O 2p and N 2p orbitals induced by the substitution of the nitrogen for the lattice oxygen. Compared to the un-doped powder, the N-doped CaNb2O6 nanoplate powder exhibited higher photocatalytic activities for the degradation of rhodamine B dye solution under visible light irradiation (> 420 nm). This higher photocatalytic activity was attributed to the higher optical absorption (smaller band gap) and higher surface area resulting from the nitridation process. PMID- 20352779 TI - Study on nanocomposites based on carbonate@ceria. AB - Nanocomposites based on the ceria-carbonate composite have demonstrated as electrolytes in development of successful 300-600 degrees C fuel cell technology. In this paper, the nanocomposite electrolyte based on carbonate@SDC (SDC: samarium doped ceria) was directly synthesized from the co-precipitation method and characterized by XRD, SEM, TEM, BET, etc. It was proved that the carbonate@SDC was a two-phase material with average particle size about 14.5 nm (S(BET)) and crystalline size (D(XRD)) ranged from 12 to 14 nm. When the carbonate@SDC electrolyte was used to fabricate single SOFC, the cell shows remarkable performance with maximum power density 1000-1180 mw/cm2 at low temperature (300-550 degrees C). PMID- 20352780 TI - Fullerite crystal thermodynamic characteristics and the law of corresponding states. AB - The existence of single-wall carbon nanotubes in organic solvents in the form of clusters is discussed. A theory is developed based on a bundlet model, which enables describing the cluster-size distribution function. Comparison of calculated solubilities with experiments would permit obtaining energetic parameters, characterizing the interaction of a nanotube with its surrounding. Fullerenes and nanotubes are objects whose behaviour in many physical situations is characterized by peculiarities, which show up in that these systems represent the only soluble forms of carbon, what is related to their molecular structures. The fullerene molecule is a virtually uniform closed spherical-spheroidal surface and a nanotube is a smooth cylindrical unit. Both structures give rise to weak interactions between the neighbouring units in a crystal and promote their interaction with solvent molecules. The phenomena have a unified explanation in the bundlet model, in which the free energy of a nanotube in a cluster is combined from two components: a volume one proportional to the number of molecules n in a cluster and a surface one proportional to n1/2. Growth mechanisms of fractal clusters in fullerene solutions are analyzed along with similarity laws, determining the thermodynamic characteristics of fullerite crystals. In accordance with the similarity laws, the dimensionless Debye temperatures theta0 for all crystals belonging to the considered class should be close. Temperatures theta0 are determined by a similarity relation from experimental and estimated data. Fullerite theta0 is twice that for inert-gas crystals because, near the Debye point, the fullerite crystal is orientationally ordered so that its structure is dissimilar to face-centred cubic. A fullerene molecule whose thermal rotation is frozen cannot be considered as a spherically symmetric particle. The fulfilment of the similarity laws, which are valuable for particles with spherically symmetric interaction potential, would hardly be expected. PMID- 20352781 TI - Iron oxide-based nanoparticles with different mean sizes obtained by the laser pyrolysis: structural and magnetic properties. AB - Nano-sized iron oxide-based particles have been directly synthesized by the laser induced pyrolysis of a mixture containing iron pentacarbonyl/air (as oxidizer)/ethylene (as sensitizer). In this paper we further demonstrate the possibility to vary the chemical composition and the nanoparticle dimensions of the iron oxide-based materials by handling the oxidation procedure in the frame of the laser pyrolysis process. Thus, nanoparticles with major maghemite/magnetite content may change composition into mixtures with variable amounts of three components: major gamma-Fe2O3/Fe3O4 iron oxide, metallic Fe and cementite Fe3C. By X-ray diffraction (XRD) it is found that the relative proportion of these phases differs in function of the reaction temperature (laser power). As revealed by transmission electron microscopy (TEM), mean particle sizes between about 4 nm and 6 nm and between about 9 and 11 nm may be prepared by varying the oxidation procedure and the laser power, respectively. By the controlled heating of samples (maximum temperature 185 degrees C), increased crystallinity for the gamma-Fe2O3/Fe3O4 oxide phase was found as well as an increase of the mean particle diameters. The examination of the magnetization curves for samples obtained for different laser powers indicates notable differences in the magnetic behavior and parameters. The temperature dependent Mossbauer measurements confirm the formation of larger particles at higher laser power densities as well as the presence of inter-particle magnetic interactions. On this basis, the estimation of phase composition for the different representative samples is given. PMID- 20352782 TI - Nanocarbonitride precipitation contribution to the yield stress of a V-Nb microalloyed steel. AB - Nanocarbonitride precipitation during thermomechanical processing is well known as one of the important mechanisms to increase mechanical properties of hot rolled microalloyed steels. Some studies of industrial hot rolled strips have quantified the contribution of the different ways of precipitation: in austenite, at the interface austenite/ferrite, or in supersaturated ferrite during final cooling. Thin slabs of microalloyed steels (0.07-0.08% V and 0.02-0.04% Nb) were thermomecanically processed on a laboratory-scale rolling mill. The different modes of nanocarbonitride precipitation were investigated by transmission electron microscopy. It was observed interphase precipitation with average diameter of nanocarbonitride of 4.4 nm and potential contribution to strengthening of 90 MPa, according to the Orowan-Ashby model. From the Orowan Ashby model of precipitation strengthening, strength contributions of about 50 MPa were found for nanocarbonitride particles formed in austenite. The inclusion of a holding extra period of 15 minutes just below the Finishing Rolling Initial Temperature has confirmed an important contribution to the yield stress given by the nanocarbonitride particles formed in austenite. PMID- 20352783 TI - Characterization of carbon nanofibre-reinforced polypropylene foams. AB - In this paper, carbon-nanofibre-reinforced polypropylene foams were prepared and characterized regarding their foaming behaviour, cellular structure and both thermo-mechanical as well as electrical properties. Polypropylene (PP) nanocomposites containing 5, 10 and 20 wt% of carbon nanofibres (CNF) and a chemical blowing agent were prepared by melt-mixing inside a twin-screw extruder and subsequently water-cooled and pelletized. The extruded nanocomposites were later foamed using a one-step compression-moulding process. The thermo-mechanical properties of the CNF-reinforced PP foams were studied, analyzing the influence of the carbon nanofibres on the cellular structure and subsequent thermo mechanical behaviour of the foams. Carbon nanofibres not only seemed to act as nucleating agents, reducing the average cell size of the foams and increasing their cell density for similar expansion ratios, but also helped produce mechanically-improved foams, even reaching for the 20 wt% CNF-reinforced ones a specific modulus around 1.2 GPa x cm3/g for densities as low as 300 kg/m3. An increasingly higher electrical conductivity was assessed for both the solids as well as the foams with increasing the amount of carbon nanofibres. PMID- 20352784 TI - Tailoring magnetic nanoparticle for transformers application. AB - In this study photoacoustic spectroscopy was used to investigate the effect of dilution of an oil-based magnetic fluid sample on the magnetic nanoparticle surface-coating. Changes of the photoacoustic signal intensity on the band-L region (640 to 830 nm) upon dilution of the stock magnetic fluid sample were discussed in terms of molecular surface desorption. The model proposed here assumes that the driving force taking the molecules out from the nanoparticle surface into the bulk solvent is the gradient of osmotic pressure. This gradient of osmotic pressure is established between the nanoparticle surface and the bulk suspension. It is further assumed that the photoacoustic signal intensity (area under the photoacoustic spectra) scales linearly with the number of coating molecules (surface grafting) at the nanoparticle surface. This model picture provides a non-linear analytical description for the reduction of the surface grafting coefficient upon dilution, which was successfully-used to curve-fit the photoacoustic experimental data. PMID- 20352785 TI - Biodegradable poly(L-lactic acid)-lavender nanocapsules: synthesis, controlled release, and application in remedy of sleep disorder. AB - In this study, nanocapsules of poly(L-lactic acid) (PLLA) containing lavender oil were synthesized by solvent evaporation emulsion. Poly(L-lactic acid) is a biodegradable aliphatic polyester derived from lactic acid formed by bacterial fermentation of glucose-rich substances. Lavender oil is a plant extract that finds uses in phytotherapy. It is reputed as anti-septic, anti-depressant and sleep promoter. Encapsulation is a technique used to encase tiny oil droplets with a thin and permeable coating that allows for a controlled release of the volatile oil. The size and morphology of the nanocapsules were characterized by scanning electron microscope. The particle size and distribution were measured by photon correlation spectroscopy. The time-controlled release of the lavender oil was studied and the use of the lavender capsules in the remedy of sleep disorder was investigated. PMID- 20352786 TI - Beta-PbO micro-octahedrons synthesized by electrochemical reduction. AB - We developed a simple and effective method to fabricate lead oxide micro octahedrons by electrodeposition with higher current density. The electrolyte was lead nitrate aqueous solution containing some drops of concentrated hydrochloric acid. Stainless steel plate was employed as both cathode and substrate, and graphite plate as anode. The controlled current that was supplied by a direct current power supply passed through the electrolyte to deposit lead oxide micro octahedrons on the surface of stainless steel at room temperature and was enhanced to more than 15 mA/cm2. The obtained deposits on cathodic substrate mainly are lead oxide regular octahedrons, which morphology and structure are confirmed by scanning electron microscopy, transmission electron microscopy and X ray diffraction. The formation of lead oxide micro-octahedrons was affected significantly by the reduction current density. Our results indicated that well shaped lead oxide micro-octahedrons could be formation at current densities in the range of 15-25 mA/cm2. PMID- 20352787 TI - The effect of polymer matrices in the in-situ CdS formation under UV irradiation of precursor-polymer films. AB - Polymer films embedding cadmium thiolate precursors have been irradiated with ultraviolet laser pulses resulting in the formation of cadmium sulfide crystalline nanoparticles through a macroscopically non-destructive procedure for the host matrix. Controlling the number of the incident laser pulses, the gradual increase of the size of the nanoparticles is accomplished, and consequently the progressive change of the emission characteristics of the formed nanocomposites. The X-ray diffraction and transmission electron microscopy measurements were used for the full characterization of the nanoparticles. This study compares two polymer matrices, poly(methyl methacrylate) and a cyclic olefin copolymer, and reveals the importance of each one for the emission characteristics of the formed cadmium sulfide nanocrystals. It is found that the poly(methyl methacrylate) matrix contributes to the increase of the trap states on the surface of the formed nanocrystals, causing the broadening of their emission. On the other hand the cadmium sulfide nanoparticles, grown into the cyclic olefin copolymer matrix, exhibit narrower emission spectra. PMID- 20352788 TI - Colour tuneability in sol-gel nano-glass-ceramics comprising Yb(3+)-Er(3+)-Tm3+ Co-doped NaYF4 nanocrystals. AB - White light can be obtained by up-conversion processes in a cheap and efficient way, being of great interest for lighting, displays, and photonic integrated devices. Here we report a generation of white light under 980 nm laser infrared excitation in Y(b3+)-Er(3+)-Tm3+ triply doped sol-gel derived nano-glass-ceramics containing NaYF4 nanocrystals where co-dopants ions are partitioned. Efficient simultaneous blue, green, and red up-conversion emissions give rise to a balanced white overall emission and corresponding up-conversion mechanisms have been analyzed. Changes in pump power intensity or heat treatment temperature widely vary the ratio of emission bands, resulting in a colour tuneability which has been analyzed and quantified in terms of CIE standard chromaticity diagram. PMID- 20352789 TI - The effect of magnetron pulsing on the structure and properties of tribological Cr-Al-N coatings. AB - The paper will discuss the effect of pulsing single or two unbalanced magnetrons in a closed magnetic field configuration on the structure and properties of tribological Cr-Al-N coatings. Nanocrystalline Cr-Al-N coatings were reactively deposited from Cr and Al elemental targets using two unbalanced magnetrons, which were powered in both dc, pulsing only Al target and asynchronously pulsing both Cr and Al targets at 100 kHz and 50% duty cycle conditions. The ion energy distributions of these deposition and pulsing conditions were characterized using a Hiden Electrostatic QuadruPole Plasma Analyzer. It was found that pulsing two magnetrons asynchronously at 100 kHz and 50% duty cycle produced higher ion energies and significant increased ion fluxes than pulsing none or pulsing only one (Al) target. The structure and properties of Cr-Al-N coatings synthesized under different dc and pulsing conditions were investigated using X-ray diffraction, scanning electron microscopy, nanoindentation and ball-on-disk wear test, and were correlated with the effects of ion energies and ion flux regimes observed in the plasma diagnostics. The advantages of using pulsed magnetron sputtering producing different energetic ion regimes to enhance the ion bombardment on the growing films and therefore achieving the improved density, refinement of grain size and properties are illustrated. PMID- 20352790 TI - Scaling laws for multi-walled carbon nanotube growth by catalyzed chemical vapor deposition. AB - The synthesis of C nanotubes by catalyzed chemical vapor deposition at 600 degrees C is investigated, using yield and purity degree of C deposits to monitor the reaction outcome. From the reaction, carried out in C4H10-H2-He environment over Al2O3 supported Fe catalysts, multi-walled C nanotubes are attained, which, after purification, are analyzed by routinely-used diagnostics techniques. In order to clarify the role of the growth parameters, various experiments are performed changing flow rates of reactive gases, as well as, amount, metal load and reduction temperature of Fe/Al2O3 catalysts in the ranges 15-90 cc/min, 0.25 2.00 g, 10-40 wt% and 500-700 degrees C, respectively. Correspondingly, carbon yield varies between 47 wt% and 913 wt%, while purity degree between 56 wt% and 93 wt%. Owing to the lack of any correlation between these changes, it is initially quite difficult to envisage the effect, produced by any change of the growth conditions, on the final reaction outcome. The problem is solved by applying a semi-empirical approach, through which the "original" growth variables are combined to give dimensionless arguments (scaling laws for the reaction parameters), able to account for all the variation of yield and purity in the ranges considered. As final result, the growth issue can be easily predicted because carbon yield and purity degree can be approximated through very simple functions of the "new" process variables. PMID- 20352791 TI - Thermal annealing and electrochemical purification of multi-walled carbon nanotubes produced by camphor/ferrocene mixtures. AB - Multi-walled carbon nanotubes (MWCNT) were obtained by pyrolysis of camphor/ferrocene mixtures, at different concentrations of ferrocene, on quartz, polished silicon and carbon felt substrates. A detailed study by electron microscopy, Raman spectroscopy, X-ray diffraction and thermogravimetric analysis was carried out to determine the purity degree of MWCNTs. Thermal annealing under vacuum and electrochemical purification were used for iron removal. The thermal annealing brings improvement on crystalline structure of MWCNTs, besides iron elimination from internal structure of the tubes, while the electrochemical treatments remove efficiently the iron from MWCNT surface. PMID- 20352793 TI - Plasmonic modes confined in nanoscale thin silver films deposited onto metallic substrates. AB - Collective electronic excitations in nanoscale thin Ag layers adsorbed on Cu(111) and Ni(111) at room temperature have been investigated by high-resolution electron energy loss spectroscopy. Surface plasmon was found to be confined within grains on Ag thin films on Cu(111) nanostructured in islands. Annealing removed surface plasmon confinement and induced a negative linear term of the dispersion relation. On the other hand, on flat thin films on Ni(111) the dispersion of Ag surface plasmon is fully quadratic. Landau damping processes of the plasmonic excitation were found to be dependent on the growth mode. Ag multipole surface plasmon at 7.7 eV was observed only under stringent kinematic conditions enhancing surface sensitivity. PMID- 20352792 TI - Characterization of highly oriented organoclay/ poly(methyl methacrylate) moulded nanocomposites. AB - In the present paper, the effects of nanoparticles' content and orientation were studied on the structure, phase morphology and thermo-mechanical properties of highly oriented montmorillonite/ poly(methyl methacrylate) moulded nanocomposites. The nanocomposites were compounded using a co-rotating high-shear twin-screw extruder. Square plates were prepared by a two-stage compression moulding process from the previously extruded materials, with the test specimens being directly machined in both parallel and perpendicular directions with respect to the plate's surface. Wide-angle X-ray diffraction (WAXD) revealed a highly-ordered structure of silicate platelets parallel to the plate's surface. Observations by transmission electron microscopy (TEM) supported this analysis, demonstrating the high anisotropy degree of the nanocomposites. Dynamic mechanical thermal analysis (DMTA) showed that the perpendicular specimens were stiffer than the parallel ones, with the presence of the oriented nanoparticles decreasing PMMA's mobility during the glass transition, although no significant differences were registered in the T(g) temperatures with increasing the amount of clay content or with orientation. Remarkable improvements regarding the fracture energy were observed for the perpendicular specimens, with the 20 wt% oMMT nanocomposite showing a fracture energy almost 10 times that of pure PMMA. PMID- 20352794 TI - Organic photovoltaic cells based on ZnO thin film electrodes. AB - Due to its wide band-gap (ca. 3.4 eV), ZnO is a possible candidate material to be used as transparent electrode for a new class of photovoltaic (PV) cells. Also, an increased interest for the photovoltaic properties of several organic monomers and polymers (merocyanines, phthalocyanines and porphyrins) was noticed, because of their high optical absorption in the visible region of the spectrum allowing them to be used as potential inexpensive materials for solar cells. Preparation and properties of CuPc (copper phthalocyanine) based photovoltaic cells using ZnO thin films as transparent conductor electrodes are presented in this paper. ZnO layers are grown by pulsed laser deposition, while the organic layers are obtained by thermal evaporation. Structural characterization is performed by electron microscopy. Optical and transport properties of the mutilayered structures are obtained by electrical and spectro-photometric measurements. The influence of the ZnO-polymer interface on the external quantum efficiency (EQE) of the photovoltaic cell is clearly evidenced by our measurements. PMID- 20352795 TI - Residual stress of free-standing membranes of yttria-stabilized zirconia for micro solid oxide fuel cell applications. AB - The present study is devoted to analyze the compatibility of yttria-stabilized zirconia thin films prepared by pulsed laser deposition and metalorganic chemical vapor deposition techniques, with microfabrication processes based on silicon technologies for micro solid oxide fuel cells applications. Deposition of yttria stabilized zirconia on Si/SiO2/Si3N4 substrates was optimized for both techniques in order to obtain high density and homogeneity, as well as a good crystallinity for film thicknesses ranging from 60 to 240 nm. In addition, stabilized zirconia free-standing membranes were fabricated from the deposited films with surface areas between 50 x 50 microm2 and 820 x 820 microm2. Particular emphasis was made on the analysis of the effect of the nature of the deposition technique and the different design and fabrication parameters (membrane area, thickness and substrate deposition temperature) on the residual stress of the membranes in order to control their thermomechanical stability for application as electrolyte in micro solid oxide fuel cells. PMID- 20352796 TI - Microstructural effects of Sn addition to Fe2O3 thin films. AB - The influence of Sn in Fe2O3 thin films is addressed. The presence of the tin ions decreases the Fe2O3 particle sizes and surface roughness decreasing of the films' surface is observed as a consequence. X-ray diffraction and atomic force microscopy measurements together with literature results support this phenomenon to be related to the segregation of the additive onto the surface and consequently surface energy decrease, which constitutes the driving force for the microstructure modification, similarly to results previously obtained for powders with same compositions. The effect of the anions introduced in the system as counter-ions of the precursors is also discussed. PMID- 20352797 TI - Influence of colloidal silver nanoparticles on the novel flower-like titanium dioxide oxygen sensor performances. AB - Titanium dioxide (TiO2-anatase phase) thin films, consisting of agglomerated flower-like nanoparticles, have been synthesized using an ultrasonic spray pyrolysis (USP) method in combination with titanium (IV) oxide acetylacetonate [TiO(acac)2], and methanol at 550 degrees C. These thin films were subsequently thermally treated in air, at 950 degrees C for six hours, and the flower-like particles were transformed into smooth surfaces mainly formed by the TiO2-rutile phase. In order to prepare oxygen sensors of good performance, TiO2 thin films were deposited on interdigitated gold electrodes with contacted alumina substrates. The silver colloidal solution was impregnated on the TiO2 thin film. Since the solvent in which the silver nanoparticles are suspended evaporates at 200 degrees C, the thin films were then annealed at this temperature in air for one hour. The effect of colloidal silver nanoparticles on the response of the thin films TiO2 oxygen sensors has been studied, in a mixture with zero-grade air. The gas-sensing properties of TiO2 sensors in an atmosphere of 10(4) ppm of oxygen were measured between 25 and 500 degrees C. The experimental results obtained with colloidal silver nanoparticles as surface additive show that the sensitivity to an O2 concentration of 100 ppm in zero grade air at 300 degrees C reaches a stationary value of 0.40, and 0.03, for TiO2-anatase and -rutile phase films, respectively. This values are as high as those reported for oxygen sensors prepared by more expensive techniques. PMID- 20352798 TI - The role of polyhedral oligomeric silsesquioxane on the thermo-mechanical properties of polyoxymethylene copolymer based nanocomposites. AB - Hybrid nanocomposites formed with polyoxymethylene copolymer (POM) and different types of polyhedral oligomeric silsesquioxane (POSS) nanoparticles have been investigated. Four types of POSS have been studied in contents of 2.5% and 5% wt. The POSS were incorporated by direct melt-mixing. Traditionally copolymerization has been the preferred approach used to form polymer-POSS nanocomposites because the possibility of immiscibility with the polymer matrix is reduced. However, melt-blended POSS nanoparticles can also improve the thermo-mechanical properties of some polymers. Different morphologies were obtained depending on the type of POSS used. GI-POSS and O-POSS exhibit sub-micron or micron-sized inclusions which size increased with increasing percentages of POSS added. On the other hand, both G-POSS and T-POSS appeared to be uniformly dispersed in the POM matrix probably at a molecular level. This is a clear indication of miscibility between these systems and also that POSS solubility in POM is higher than 5 wt%. G-POSS improved the thermal stability of the systems. However, the melting temperature and the modulus of elasticity were found to slightly decrease. On the other hand, the O-POSS produced the opposite effect in the matrix. Finally T-POSS filled systems do not yield important variations in regard to polymethylene oxide properties although interaction between T-POSS and the matrix was detected. PMID- 20352799 TI - Synthesis and characterization of nano-particulate BaTiO3 for ceramic/polymer composite capacitor. AB - BaTiO3 nano-particles with a size range of 20-70 nm were synthesized at 70 degrees C through a simple wet-chemical reactions between barium hydroxide octahydrate (Ba(OH)2 x 8H2O) and meta titanic acid (H2TiO3) in ethanol/water mixed solvent systems. It was found that the volume ratio of ethanol to deionized water is a key controlling parameter to determine the phase formation and particle size of BaTiO3. Single-phase cubic perovskite BaTiO3 started to be formed in solution containing above 40 volume percent of ethanol. From the field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) analysis, the as-prepared BaTiO3 exhibited the aggregated morphologies. The surface properties were characterized by the nitrogen adsorption isotherms curves. The effects of these aggregates on the electrical performance in BaTiO3/epoxy nano-composites were also examined. PMID- 20352800 TI - Thrombocompatibility of thin dielectric carbon film dependence on electron work function of metallic substrate material. AB - We demonstrate here for the first time the relationship between electron work function of metallic substrate material, used for coating with thin dielectric carbon (DC) film, and surface thrombocompatybility of this structure. Thin dielectric layers of DC, with thickness below 1 microm, were deposited on medical steel 316L, titanium alloy Ti6Al4V and titanium nitride (TiN) using the RFCVD method. The values of the DC coated metallic electrode potential in water and in serum and the number of adhered blood platelets to the DC coated metals depended on the electron work function (phiM) of the metallic substrate. As the phiM increased, the electrode potentials increased, whereas the number of adhered blood platelets decreased. This effect permits controlling the interaction between blood and the thin DC films by selecting an appropriate metallic substrate. PMID- 20352801 TI - Electrochemical deposition of ZnO nanostructures. mechanism of growth. AB - The growth kinetics of ZnO nanorods were studied by means of an electrochemical deposition process on ITO electrodes submerged in an aqueous solution of 5 mM ZCl+0.1 M KCl at 80 degrees C. The stages of the growth kinetics showed a mechanism of formation of nano-spheres which with time were transformed into hexagonal crystals of ZnO. Cathodic current densities of 0.1 to 1 mAcm2 formed hexagonal columns of 800 nm thickness while stronger currents formed a high density layer of cylindrical nanorods 80 nm in diameter. An amorphous barrier layer was found between the surface of the electrode and the base of the nano columns. The conditions assayed showed the possibility of adjusting the morphological characteristics of the layer in order to obtain different properties in different applications. PMID- 20352802 TI - Charge transport and trapping in bulk-heterojunction solar cells. AB - Charge carrier transport and trapping was investigated in organic solar cell structures consisting of poly-3-hexylthiophene blended with the fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester in 6:5 weight ratio. The analysed devices having solar efficiency of 3.7 per cent were produced in the inverted layer sequence. The fill factor of the IV characteristics was as high as 68 per cent. It was demonstrated that despite of such relatively high fill factor carrier trapping is effectively involved in the charge transport phenomena. The density of the trapping states was evaluated to be up to 10(20) division by 7 x 10(21) cm(-3) and their activation energy was about 0.18 eV. At such high densities these states may probably act as transport states, limiting carrier mobility. The results were analyzed by taking into account carrier thermal generation from traps as well their mobility variation according to the Gaussian disorder model. The mobility parameters obtained by both methods demonstrated good coincidence. PMID- 20352803 TI - Reclamation system design of nanostructured coatings of touch-panel. AB - A newly design reclamation system using an ultrasonic micro electroetching (UMECE) as a machining process for Indium-tin-oxide(ITO) nanostructured coatings dissolved from a surface of polyethyleneterephthalate (PET) of touch-panel is presented. The design features of the reclamation mechanism and a designed wedge form tool are of major interest. The low yield of ITO nanostructured coatings is an important factor in optoelectronic semiconductor production. In the current experiment, a small diameter of the anode accompanying with a small distance between the two anodes, reduced the amount of time for effective ultrasonic micro electroetching of ITO since the effect of removal is facilitated by supplying sufficient electrochemical power. The performance of ultrasonics was found to be more effective than pulsed current, requiring no increase in electric power. Additionally, electric power, when combined with a fast feed rate, provides highly effective dissolution. Higher frequency or the greater power of ultrasonics corresponds to a higher dissolution rate for ITO nanostructured coatings. A small anode of the wedge-form tool or a small size of the cathode takes less time for the same amount of ITO removal. Importantly, ultrasonic micro electroetching with the designed wedge-form tool requires only a short period of time to dissolve the ITO's nanostructured coatings easily and cleanly. PMID- 20352804 TI - Doped nanostructured zinc oxide films grown by electrodeposition. AB - ZnO thin films doped with either In or Al are n-type oxide materials of interest for application in electronic devices and thin-film solar cells. In this work, the doped ZnO films were electrodeposited at 80 degrees C from an aqueous solution on polycrystalline conductive Indium Tin Oxide covered glass substrates. The incorporation of the dopants into the ZnO film has been verified by energy dispersive X-ray spectrum, X-Ray diffraction and optical transmission analysis. The optical and surface structure properties of the ZnO doped films are strongly affected by the In and Al concentrations in the electrodeposition solution as evidenced by optical transmission and reflection measurements, and scanning electron microscopy. PMID- 20352805 TI - Synthesis and characterization of V1-xMo(x)O2 thermochromic coatings with reduced transition temperatures. AB - In this study Mo-doped VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC magnetron sputtering. Structural analyses, carried out at room temperature, revealed single-phase monoclinic VO2 with preferred crystal orientation in the (002) direction, regardless the Mo doping concentration. The surface morphology of the films revealed elongated grains dispersed randomly with decreasing sizes for higher Mo doping concentrations. The measured roughness parameters showed an opposite tendency, i.e., increased for higher Mo doping contents. The optical analyses showed films with maximum optical transparencies in the visible range from 35 to 45% and decreased IR modulation capacity from 36 to 25% with increasing Mo content from 3 to 11%. The Mo dopant concentration in the film was found to have a linear influence on the phase transition temperatures, showing a decrease of about 3 degrees C per at% of Mo. Phase transition temperatures as low as 32 degrees C were obtained. PMID- 20352806 TI - On physical nanoscale aspects of compatibility of steels with hydrogen and natural gas. AB - The possibilities of effective solutions of relevant technological problems are considered based on the analysis of fundamental physical aspects, elucidation of the nano-structural mechanisms and interrelations of aging and hydrogen embrittlement of materials (steels) in the hydrogen industry and gas-main industries. The adverse effects which these mechanisms and processes have on the service properties and technological lifetime of materials are analyzed. The concomitant fundamental process of formation of carbohydride-like and other segregation nanostructures at dislocations (with the segregation capacity 1 to 1.5 orders of magnitude greater than in the widely used Cottrell 'atmosphere' model) and grain boundaries is discussed in the context of how these nanostructures affect technological processes (aging, hydrogen embrittlement, stress corrosion damage, and failure) and the physicomechanical properties of the metallic materials (including the technological lifetimes of pipeline steels). PMID- 20352807 TI - Chemistry of porous coordination polymers having multimodal nanospace and their multimodal functionality. AB - Remarkable advances in the recent development of porous coordination polymers (PCPs) or metal organic frameworks (MOFs) have paved the way toward functional chemistry having potential application such as molecular storage, separation, and catalysis. Moreover flexible PCPs, which are structurally transformable depending upon guest molecules adsorption/desorption, have received much attention because they provide unique properties, dissimilar to those of zeolites. PCPs can be categorized into structurally monomodal and multimodal classes. Monomodal PCPs possess single uniform pores in the framework. In contrast, multimodal PCPs have more than two types of pores in the framework. Interpenetrated PCPs can possess more than two types of pores with different sizes and shapes in the same framework depending on relative position of individual motifs, resulting in multimodal PCPs. Moreover, interpenetrated PCPs have several advantages, such as high thermal stability, flexibility, and ultramicropore for effective adsorption. In this review, chemistry of PCPs based on monomodal and multimodal PCPs are summarized and discussed. PMID- 20352808 TI - Recent developments in supramolecular approach for nanocomposites. AB - One of the most efficient ways to create new materials is the fabrication of nanocomposites and/or nanohybrids. Composites adopt some characteristics from the components that compose it; synergistic effects can also produce properties not present in any of the parts. A union of the worlds of organic, biological, and inorganic materials merges the versatility, fine structural precision, and mechanical and chemical stability of these respective areas. In this short review, we introduce recent developments of supramolecular approaches for nanocomposite fabrications mainly based on LbL assembly, LB films, and mesoporous structures, as well as incorporation of various supramolecular components into composites. PMID- 20352809 TI - Pyridine-2,4-dicarboxylate: a versatile building block for the preparation of functional coordination polymers. AB - The hydrothermal reaction of the pyridine-2,4-dicarboxylate (2,4-pdc) dianion with various 3d metal(II) cations resulted in the formation of a series of one-, two- and three-dimensional coordination polymers with varied network topologies. 2,4-pdc reacted directly with MnCI2 or FeCl2 in water at 200 degrees C under mild basic conditions to give a dense three-dimensional polymer, [M(2,4-pdc)] (M = Mn, 1a; M = Fe, 1b), which supports a highly-connected three-dimensional magnetic exchange lattice. Both 1a and 1b undergo antiferromagnetic ordering and the latter Fe(II)-containing material exhibited spin-canting behavior below 6.5 K. Reaction of 2,4-pdc with CoCl2 under identical conditions gave an unusual zigzag chain polymer, [Co4(2,4-pdc)4(OH2)10] (2), that has large amounts of coordinated H2O. The magnetism of 2 based on isolated Co(II) dimers was modeled using a modified van Vleck approach. Adjustment of the reaction pH resulted in the formation of additional Co(II)-containing materials with strongly contrasting structures: at lower pH in the presence of oxalic acid, the same reaction components gave a protonated molecular species, [Co(2,4-pdcH)2(OH2)2]. 2H2O (3); at higher pH in the presence of excess hydroxide, a highly porous, three dimensional material was obtained, [Co3(micro3-OH)2(2,4-pdc)2] x 9H2O (4a). 4a contains cobalt hydroxide chains, whose magnetic behavior has been studied in detail by neutron diffraction. A Ni(II)-containing analogue was also prepared using NiCI2 (4b), which shows weak antiferromagnetic coupling. Attempts to obtain a Zn(II)-based analogue of the porous material 4 gave instead a unique coordination material, [Zn(micro2-OH)2(2,4-pdc)] (5), which contains uncommon zinc hydroxide bridging modes. PMID- 20352810 TI - Interaction of hydrogen with extraframework cations in zeolite hosts probed by inelastic neutron scattering spectroscopy. AB - The hindered rotations of molecular hydrogen adsorbed at low loadings into a number of partially ion-exchanged zeolites A, Y and X have been studied at low temperatures with the use of inelastic neutron scattering (INS) techniques. The factors that determine the sorption sites and strength of the interaction with the host material are found to be a complex combination of the type, charge and size of the cations, their coordination to the host framework, and accessibility to the hydrogen molecule as well as the relative acidity of the framework, and lead to important criteria for the development of more effective hybrid materials for hydrogen storage. The highest barriers to rotation were found for the undercoordinated, exposed Li+ cations in LiA and in LiX. Interaction with the extra framework Cu2+ and Zn2+ cations in zeolite A is found to be noticeably stronger than with the neutral Zn- or Cu- containing clusters in metal-organic framework compounds. Our observation that binding of hydrogen in these charged frameworks is strongly enhanced relative to those that are neutral suggests an important approach to improvement of porous materials as ambient temperature hydrogen storage media. PMID- 20352811 TI - Nanohybrids of ultrathin titania nanosheets and zinc oxide nanoparticles by an electrostatic interaction. AB - We synthesized ultrathin titania nanosheets and zinc oxide nanoparticles, and formed the nanohybrids of them by an electrostatic interaction. The titania nanosheets were prepared by soft chemical processes: intercalation, exfoliation, and reassembly. The zinc oxide nanoparticles were prepared by the sol-gel method. And two nano-scale inorganic materials were hybridized to form nanohybrids using an electrostatic interaction as a driving force. According to the X-ray diffraction pattern and high-resolution transmission electron microscope images, it is revealed that the nanohybrid of the titania nanosheets and zinc oxide nanoparticles has a house of cards structure in which zinc oxide nanoparticles are randomly attached to layered titania nanosheets. PMID- 20352812 TI - Effect of a sintering process on the electrical properties of SnO2 gas sensors. AB - SnO2 is a widely used sensor material that exhibits high sensitivity. It is known for its complex sensing characteristics, and its microstructure is an important parameter related to electrical properties and mechanical rigidity. Understanding of its microstructural effects is therefore essential to examine sensing mechanisms that may apply to industrial devices. In this work, the effect of a sintering process on the electrical properties is investigated. The sintering temperature and the relative density were chosen as process variables. The grain size of the specimen increased as the sintering temperature increased, whereas the relative density did not change. The apparent activation energy for conduction varied as the compacting pressure and the sintering conditions changed. Samples with a high density and large particle size showed low activation energy for conduction and low sensitivity at 375 degrees C. In an attempt to improve the properties, the powder was heat-treated at 1000 degrees C for 10 hours before compacting and sintering. The samples with heat-treated powder showed a slight decrease in the activation energy depending on the density and comparable sensitivity compared to non-treated powder at a high density. Pre treatment of powder can be a simple means of thermal stability under high operating temperatures. PMID- 20352813 TI - High frequency properties of Fe-Si nano-powder/epoxy films. AB - Composites of Fe93.5Si6.5 powder and epoxy (diglycidyl ether of bisphenol A type) were prepared using an electron beam irradiation process. Scanning electron microscope (SEM), vibrating sample magnetometer (VSM) and network analyzer were used to analyze the structure, electromagnetic properties and micro wave absorption of the composites. Results show that the saturation magnetization depends on the fraction of the Fe93.5Si6.5 powder in the composite, which affects initial permeability. It is believed that the eddy current loss is a dominant factor over 1 GHz and that the resonance frequency of the composite decreases with increasing fractions of Fe93.5Si6.5 powder. Finally, reflection loss was calculated from the permeability and permittivity of these composites. Composite with 50 wt% Fe93.5Si6.5 powder fractions and 5 mm thickness showed reflection loss below -20 dB from 3.66 GHz to 4.16 GHz. Therefore, it is believed that thin Fe-Si/epoxy composites may be a good candidate for microwave absorption application. PMID- 20352814 TI - Mechanical and electrical properties of carbon nanotube/Cu nanocomposites by molecular-level mixing and controlled oxidation process. AB - A molecular-level mixing and controlled oxidation process is proposed as a novel fabrication technique for the production of CNT/Cu nanocomposite powders. The fabricated CNT/Cu2O nanocomposite powders showed microstructures with homogeneous dispersion of implanted CNTs in a Cu2O matrix. The CNT/Cu2O nanocomposite powders were reduced to CNT/Cu nanocomposite powders with H2 gas and then the as-prepared CNT/Cu nanocomposite powders were spark plasma sintered to fabricate CNT/Cu nanocomposites. The mechanical properties of the Cu and the CNT/Cu nanocomposites were characterized by tensile testing before and after hot compression. Before hot compression, the CNT/Cu nanocomposites were brittle, but after hot compression both yield strength and elongation were increased, while the yield strength of the Cu was decreased after hot compression. Hot compression enhanced the ductility and strength of the CNT/Cu nanocomposites due to alignment of Cu grains and CNTs. Electrical conductivity was also enhanced due to a reduced scattering of electrons because of the alignment of the CNTs and Cu grains as well as the annealing effects of the Cu matrix. PMID- 20352815 TI - Surface analysis of a nano-sized oxide formed on alloy 600 in a high temperature/pressure aqueous solution. AB - Even though nickel based Alloy 600 (Ni 75 wt%, Cr 15 wt% and Fe 10 wt%) shows superior corrosion and mechanical properties, numerous corrosion problems, caused by a long time exposure of more than 30 years under a high temperature and high pressure water chemical environment have occurred. Especially, a lead induced stress corrosion cracking (SCC) has been a very important issue. A SCC is deeply related to a nano-sized oxide properties, formed on an Alloy 600 surface, because a crack initiates and propagates through a breakdown and modification of a thin surface oxide formed naturally on Alloy 600 in an aqueous solution. Therefore an investigation of an oxide properties would provide key information to elucidate the mechanism of a SCC and to establish a countermeasure. In the present work, a surface oxide film formed on Alloy 600 in an aqueous solution at 315 degrees C without/with a lead oxide and nickel boride as a SCC accelerator and an inhibitor, respectively, was analyzed by using a transmission electron microscopy, equipped with an energy dispersive X-ray spectroscopy and an X-ray photoelectron spectroscopy, equipped with an ion sputter for a depth profiling. In both the ammonia solutions without/with NiB, a duplex oxide layer was formed, i.e., a porous outer oxide mainly composed of NiO and Ni(OH)2 and a relatively dense inner Cr2O3 layer. Lead was incorporated into the oxide layer leading to a Cr depletion in the oxide layer and a passivity degradation. The passivity of the surface oxide was increased when NiB was added into a solution with PbO, which was in accordance with the increase of the SCC resistance. Passivity degradation by lead and the inhibitive mechanism of nickel boride were explained by a defect chemistry in an oxide semiconductor and an adhesion preference as a function of the wetting angle, respectively. PMID- 20352816 TI - Effect of spark plasma sintering on plasma electrolytic oxidation coatings on gas atomized Mg-Zn-Y alloy containing nano-sized powders. AB - Mg-1.0wt%Zn-2.0wt%Y alloy powders were produced by gas atomization, and subsequently sintered by spark plasma sintering (SPS). The SPSed Mg-1.0wt%Zn 2.0wt%Y alloy, which showed a microstructure of well-bonded grains containing nano-sized powders of approximately 100 nm in diameter, was coated by a plasma electrolytic oxidation (PEO) method. Microstructure, mechanical properties and corrosion properties of PEO coatings were investigated and compared to those of normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-1.0wt%Zn alloys. All coatings consisted of MgO and Mg2SiO4. The micro-hardness and friction coefficient of coatings on the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy were higher than those on normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-l.0wt%Zn alloys. However, the corrosion resistance in 3.5% NaCl solution for the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy was between that for normally sintered Mg-1.0wt%Zn-2.0wt%Y alloy and cast Mg-1.0wt%Zn alloy. PMID- 20352817 TI - Synthesis and characterization of a fluorene-quinoxaline copolymer for light emitting applications. AB - A conjugated copolymer based on 9,9-dioctyl-fluorene and 2,3-bis(4 (hexyloxy)phenyl) quinoxaline has been synthesized by the palladium-catalyzed Suzuki coupling reaction. The synthesized polymer was soluble in common organic solvents such as chloroform, THF, and toluene and had good film properties. The polymer was analyzed by 1H-NMR spectroscopy, UV-vis spectroscopy, GPC, TGA, DSC, and cyclic voltammetry. It had very good thermal properties with high decomposition and glass transition temperatures, 420 degrees C and 159 degrees C respectively, and a low band gap of 2.51 eV. The polymer LEDs (ITO/PEDOT:PSS/polymer/LiF/Ca/Al) showed pure green light emission with maximum peaks at 502 nm and CIE coordinates of x = 0.28 and y = 0.55. The turn-on voltage of the polymer device was 7 V and the maximum brightness was 10.16 cd/m2 at 14 V. The maximum luminescence efficiency of the polymer was 0.0011 cd/A at 11 V. PMID- 20352818 TI - Iron nanofibers synthesized by the electrospinning method for use as a GHz band electromagnetic wave absorber. AB - In this study, we fabricated Fe nanofibers that had a high aspect ratio and were coated by an oxidation protection layer, because electromagnetic properties are affected by the aspect ratio and oxidized layers. PVP/Fe salt nanofibers were prepared by an electrospinning method using an optimized concentration of PVP solution with Iron(lll) nitrate nonahydrate (Fe (NO3)3.9H2O) solution to apply a high voltage. Subsequently, to prepare the Fe nanofibers, the PVP/Fe salt nanofibers were heated up to 600 degrees C in air and reduced to 450 degrees C in H2. The Fe nanofibers were then coated by PVP to prevent re-oxidation. The S parameter of the prepared Fe nanofibers was measured by a network analyzer, and the power loss was calculated to estimate the EM absorption ability. PMID- 20352819 TI - Facile synthesis of VFI molecular sieve in the presence of triethylamine. AB - Aluminophosphate (AIPO) molecular sieve having extra-large pore (VFI structure with 18 membered rings) can be synthesized readily at 110 or 120 degrees C under microwave irradiation from a gel containing triethylamine (TEA) as a template or structure-directing agent. At high temperature of 130 degrees C, the VFI transforms into AFI with the increase of reaction time since the relative stability of VFI is less than that of AFI. Due to the rapid crystallization involved in the microwave method and instability of the porous material with extra-large pore (in this study, VFI structure), the material can be selectively synthesized only by microwave irradiation. The synthesized VFI from gel containing TEA is very stable that can be dried at 100-160 degrees C at atmospheric pressure without the phase-transformation into AIPO-8. PMID- 20352820 TI - Anodization of carbon fibers on interfacial mechanical properties of epoxy matrix composites. AB - The influence of anodic oxidation on the mechanical interfacial properties of carbon-fiber-reinforced epoxy resin composites was investigated. The surface properties of the anodized carbon fibers were studied through the measurement of contact angles and through SEM, XPS, and FT-IR analyses. The mechanical interfacial properties of the composites were studied through measurements of interlaminar shear strength (ILSS), critical stress intensity factor (K(IC)), and critical strain energy release rate (G(IC)). It was shown that the surface functional groups containing oxygen on the anodized carbon fibers exert great effects on the surface energetics of fibers and the mechanical interfacial properties, e.g., ILSS, of the resulting composites. Contact angle measurements based on the wicking rate of a test liquid showed that anodic oxidation lead to an increase in the surface free energy of the carbon fibers, mainly in its specific (or polar) component. In terms of surface energetics, it was found that wetting played an important role in increasing the degree of adhesion at interfaces between the fibers and the resin matrices of the composites. PMID- 20352821 TI - Synthesis of high thermally-stable mesoporous alumina particles. AB - The mesoporous undoped and Si-doped alumina were prepared with an ultrasonic spray process, and found to have well-developed mesopore structures and large surface areas. The mesoporous Si-doped alumina has a high thermal stability up to 1473 K. Its surface area and pore volume were found to slowly decrease with increasing temperature. Mesoporous undoped alumina is transformed to gamma alumina at 1073 K, whereas the amorphous nature of the pore walls of the Si-doped alumina is maintained up to 1073 K. When heat treatment was carried out at 1473 K for 2 h, the mesopore-networks of the undoped alumina collapsed, and then all the pore walls were converted into the alpha-alumina phase. In contrast, the mesoporosity of the Si-doped alumina persisted during heat treatment, and its pore walls were transformed to gamma-alumina. The decreases in the pore volume of the undoped alumina at 1073 K and 1473 K were found to be 36% and 99% respectively, but for the Si-doped alumina were only 24% and 36% respectively. The surface area of the undoped alumina at 1473 K was found to be 11 m2/g but that of the Si-doped samples at the same temperature is higher than 100 m2/g. Thus this mesoporous Si-doped alumina can be used as a catalytic support in reactions at high temperatures. PMID- 20352822 TI - Growth of nanostructured polycrystalline cerium oxide through a solvothermal precipitation using near-supercritical fluids. AB - Well-crystallized cerium dioxide with cubic phase were formed and self-assembly grown to nanofibers or nanosheets via a solvothermal precipitation from near supercritical fluids without any help of metal catalysts or capping agents. The self-assembly attachment process without any preferred or selective orientation dominated the growth of the polycrystalline nanofibers or nanosheets consisting of grains of approximately 3 nm to which are formed by the coalescence of the single crystalline cerium oxide seeds. The growth is attributed to be driven by phase separation due to partial compatibility between ethyl alcohol and supercritical carbon dioxide fluid during the precipitation reaction, not by different surface energies or defects. With increasing temperature, the nanofibers with a weblike network structure were formed and then fused to large spherical particles. As a result, the polycrystalline fibers or sheets consisting of pure cerium dioxide phase were produced by the solvothermal reaction with an aid of the supercritical carbon dioxide from the alcoholic metal salt solution. PMID- 20352823 TI - Solvothermal synthesis of Fe-MOF-74 and its catalytic properties in phenol hydroxylation. AB - A Fe-containing metal-organic framework, Fe-MOF-74, was solvothermally synthesized using FeCl2.4H2O and 2,5-di-hydroxy-1,4-benzenedicarboxylic acid. Characterization was conducted by XRD, BET surface area measurement, FT-IR spectroscopy, TGA, and elemental analysis, which confirmed successful preparation of Fe-MOF-74 having an identical framework structure to that reported for MOF-74. Fe-MOF-74 was found to be an effective heterogeneous catalyst for the hydroxylation of phenol using H2O2 as an oxidant; 60% phenol conversion was achieved at 20 degrees C in water with 68 and 32% selectivity to catechol and hydroquinone, respectively. The effect of temperature, phenol/H2O2 mole ratio, catalyst quantity, and solvent on catalytic performance was discussed, and a reaction mechanism is proposed based upon the experimental results. PMID- 20352824 TI - The phase analysis of spark plasma sintered MgB2 after ball milling. AB - Mg and amorphous B powders below 10 and 3 micro meter were used as raw materials, and mixed by planetary-mill for 9 hours at argon atmosphere. MgB2 bulk was fabricated at the various temperatures by Spark Plasma Sintering. In the sintering process, mixed powders were sintered in graphite mold, at the pressure of 55 Mpa. The fabricated MgB2 samples were evaluated with XRD, EDS, FE-SEM, PPMS. MgB2, MgO and Fe phases were observed from XRD result. In the results, MgO and Fe were impurity which may affect superconducting properties of MgB2 samples, and it's distribution could be confirmed from EDS mapping result. In order to confirm the formation of MgB2 phase, DTA was used as heating rate of 10 degrees C/min at Ar atmosphere from room temperature to 1200 degrees C. In the PPMS result, the Tc (critical temperature) was about 21 K, and the density of spark plasma sintered samples increased to 1.87 g/cm3 by increasing sintering temperature. PMID- 20352825 TI - Enhanced catalytic performance of copper-exchanged SAPO-34 molecular sieve in methanol-to-olefin reaction. AB - Methanol-to-olefin (MTO) reaction over copper-exchanged SAPO-34 catalysts was investigated in order to extend their catalyst life. The exchange of copper ions into the cages of an SAPO-34 molecular sieve was confirmed by ESR, XPS, and 129Xe NMR techniques. Copper ions located in its cages considerably reduced its deactivation rate in the MTO reaction, while those dispersed on the external surface of the SAPO-34 molecular sieve accelerated the deactivation due to the limited mass transfer through the pore entrances. The 13C NMR and UV-VIS spectroscopy investigations of the materials occluded on the copper-exchanged SAPO-34 catalysts during the MTO reaction clearly showed that the copper ions exchanged in the cages suppressed the further condensation of alkyl aromatics to large, fused polycyclic aromatic hydrocarbons (PAHs). Theoretical calculations for the SAPO-34 and copper-exchanged SAPO-34 molecular sieves supported this observation because copper ions located in the cages stabilized the alkyl aromatics. Therefore, the exchange of copper ions into the SAPO-34 molecular sieve stabilized the reactive intermediates, alkyl aromatics, of the MTO reaction and suppressed their further condensation to PAHs, thereby slowing the deactivation. PMID- 20352826 TI - Fabrication and electrochemical application of monolayers of well-ordered macroporous silica. AB - Highly ordered macroporous silica films with a monolayer thickness and regular array of spherical pores with diameters of about 305 nm are prepared using templates self-assembled by polymethylmethacrylate (PMMA) spheres on solid surfaces by spin coating. The macropores are uniform in size and completely exposed on the bottom surface of the film after the PMMA spheres are etched out. Based on electrochemical experiments, the film allows for easy mass transport of Ru(bpy)3(2+) to the ITO surface. Electrochemical detection of DNA hybridization was also carried out in model oligonucleotide hybrids immobilized on the macroporous silica film. PMID- 20352827 TI - Evolution of phase and morphology of titanium dioxide induced from peroxo titanate complex aqueous solution. AB - We demonstrate the growth of anatase TiO2 in nanospheres and rutile TiO2 in nanorods, by the hydrolysis of titanium tetraisopropoxide (TTIP) in the presence of hydrogen peroxide at 100 degrees C using sol-gel method. X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), and surface area measurement techniques are used to characterize the phase and shape developments of TiO2 obtained from peroxo titanate complex in an aqueous solution at 100 degrees C. Peroxo titanate complexes were prepared by a reaction of titanium hydroxide, formed by hydrolysis of titanium tetraisopropoxide (TTIP), and different amounts of hydrogen peroxide (H2O2). TEM and XRD investigations reveal that the size of spheres (anatase) and rods (rutile) are about 8 nm (diameter) and about 13 x 29 nm approximately 20 x 75 nm (width x length) respectively. The influence of molar ratio of H2O2/TTIP on the phase and morphology of TiO2 is presented. A mixture of anatase spheres and short rutile rods are formed at low H2O2/TTIP ratio while predominantly rutile a quit long rods are formed at higher H2O2/TTIP ratio. PMID- 20352828 TI - Potential application of fabricated sulfide-based scintillation materials for radiation detection. AB - In our laboratories, we have produced ZnS(Ag)/6Li sol-gel scintillation materials which produce an excellent light output with an alpha radiation (compared to commercial high temperature lithiated glass; KG-2 and a plastic scintillator; BC 400). However, when tested with a neutron radiation, the opacity of the ZnS(Ag)/6Li sol-gel scintillation materials, which were composed of a homogeneous micron-sized ZnS(Ag), prevented a clear neutron energy peak formation, thus making it difficult to set a threshold for neutron-gamma discrimination. In an effort to increase the transparency of the scintillation materials and to develop new technologies to fabricate sulfide-based scintillation materials for neutron detection, we turned to the methods of a chemical bath deposition (CBD) and a nano-particle synthesis for possible solutions. PMID- 20352829 TI - Application of nano-sized TiO2 as an inhibitor of stress corrosion cracking in the steam generator tube materials. AB - Several chemicals were studied to suppress the damage due to a stress corrosion cracking (SCC) of the steam generator (SG) tubes in nuclear power plants. SCC tests were carried out to investigate the performance of TiO2 on several types of SG tube materials. The SCC tests were conducted by using an m-RUB specimen in a 10% NaOH solution at a temperature of 315 degrees C. The test with the addition of TiO2 showed a decrease in the SCC rate for the SG tubing materials. In order to improve the inhibition property in a crevice of TiO2, a sonochemical technique was applied to reduce the size of the TiO2 particle. From the SCC tests with the RUB specimen, the SG tube materials showed an enhanced cracking resistance with the addition of nano-sized TiO2 and the surface property was also changed. PMID- 20352831 TI - Enhanced exchange-coupling effect in Nd-Fe-B/Fe-B nanocomposite magnet. AB - Soft phase magnetic Fe-B nanoparticles were prepared by coprecipitation and the hard phase magnetic Nd-Fe-B nanoparticles were obtained from mechanical ball mill of the bulk Nd-Fe-B with a shaker mill. Also mechanical ball mill technique was applied to the mixture of Nd-Fe-B and Fe-B nanoparticles to build up an exchange coupled nanocomposite magnet. It was loaded in electronic furnace and annealed under a flow of hydrogen at 953 K for 30 min. The exchange coupled interaction of isotropic magnets was characterized by smooth hysteresis loop with a high value of remanence (Mr/Ms > 0.5). PMID- 20352830 TI - Influence of nanopores of MCM-41 and SBA-15 confining (n-BuCp)2ZrCl2 on copolymerization of ethylene-alpha-olefin. AB - The effect of nanopore in mesoporous materials confining (n-BuCp),ZrCl2 and methylaluminoxane (MAO) on ethylene-1-hexene and ethylene-1-octene copolymerization was investigated on the basis of the copolymerization results, and the analysis of the supported catalyst and the copolymers. SBA-15 and MCM-41 together with amorphous silica were employed as supports, which are capable of confining (n-BuCp)2ZrCl2 and MAO in the nanopore. The copolymerization activities of MCM-41-supported (n-BuCp)2ZrCl2 were higher than those of SBA-15 and SiO2 although that its Zr content was quite lower than those of SBA-15 and SiO2. SBA 15 and MCM-41 showed a remarkable decrease in BET surface area after confining MAO and (n-BuCp)2ZrCl2 compared to SiO2, explaining an even adsorption of MAO and (n-BuCp)2ZrCl2 complexes on the nanopore surface. Temperature rising elution fractionation (TREF) results showed bimodal curves of MCM-41-supported (n BuCp)2ZrCl2 at the C6/C2 and C8/C2 molar ratios of 0.6 and 0.5, respectively, which was attributed to the differences in ethylene and alpha-olefin concentrations along with the cylindrical nanopore of MCM-41 due to the narrow nanospace. PMID- 20352832 TI - Linkage-nondestructive surface migration of zeolite microcrystals during monolayer assembly on glass through ionic linkages. AB - Monolayers of zeolite microcrystals were prepared on glass plates with three different types of linkage between zeolite crystals and the substrate, namely, (a) covalent, (b) ionic, and (c) poly electrolyte-mediated ionic linkages using sonication with stacking (SS) as the method. The required periods for the coverage to reach 100% were 2, 3, and 7 min, respectively, upon changing the linkage from (a) to (b) and to (c), respectively, indicating that the surface migration becomes slower as the binding strength increases. The coverage, binding strength, and degree of close packing gradually decreased with reaction time with (a) as the linkage while those with (b) and (c) as the linkages remain essentially unaltered. The results indicate that the surface migration of crystals undergo linkage-destructively when crystals were attached to the substrates through covalent linkages and linkage-nondestructively when crystals were attached to the substrates through ionic linkages. PMID- 20352833 TI - Physicochemical characteristics of SAPO-34 molecular sieves synthesized with mixed templates as MTO catalysts. AB - In the present work, a variety of SAPO-34 catalysts have been prepared using various templates such as a single or mixtures of tetraethylammonium hydroxide (TEAOH), morpholine, diethylamine (DEA), triethylamine (TEA), dipropylamine (DPA), isopropylamine (IPA) and Diethanolamine (DEtA). It is shown that crystal morphology and physicochemical properties were affected by the kinds of templates and mixture contents. Especially, inexpensive SAPO-34 catalyst with good crystal properties and catalytic performance was obtained by using mixed template of DEA and TEAOH. Through N2 isotherm, XRD, SEM, NH3 TPD and 29Si-NMR techniques, the effect of mixed template on the crystal morphology, acidity and Si distribution were investigated. Catalytic activity and life stability of SAPO-34 in MTO reaction was improved by using mixed template because of the distinction of the crystal size, acidity and Si distribution. PMID- 20352834 TI - Interactions between tetrahydrothiophene (THT) and silver species in AgNa-Y. AB - We studied the interaction between tetrahydrothiophene (THT), which is one of sulfur odorants in a pipeline natural gas, and AgNa-Y zeolites, which can be obtained via Ag+ exchange with Na+ of Na-Y and used for the adsorptive removal of THT at ambient temperature and atmospheric pressure, with a temperature programmed desorption (TPD), a temperature-programmed reduction with H2 (H2-TPR), a transmission electron microscopy (TEM) with an energy dispersive X-ray spectroscopy (EDX) and an X-ray absorption fine structure (XAFS). The presence of the metallic Ag and the Ag+ in the fresh AgNa-Y can be supported with a TEM and an XAFS analysis. The fraction of metallic Ag in silver species increased with increasing the pretreatment temperature. The formation of Ag-S bond with concomitant decreasing the interaction between Ag+ and oxygen in the lattice as well as the interaction of Ag-Ag in the metallic Ag can be observed during the adsorption of THT at ambient temperature. This can explain why there is no noticeable difference in the adsorption capacity in between Ag+ -dominant AgNa-Y and Ag0-rich AgNa-Y. This Ag-S bond was transformed into the Ag-Ag bond during the heat treatment in an inert gas above 673 K. However, the fresh chemical and electronic state of Ag can be recovered after the heat treatment in air above 673 K. PMID- 20352835 TI - Mechanical properties of IIR/OMMT nanocomposites via melt-compounding and solution process. AB - Isobutylene-isoprene rubber (IIR)/organically modified montmorillonite (OMMT) nanocomposites were prepared by both melt-compounding and solution process. Organic modifiers were synthesized by the reaction of allyl bromide and alkyl amines to modify sodium montmorillonite (Na+ -MMT). After modification of Na+ MMT with organic modifiers, the changes of d-spacing of OMMT were studied by X ray diffraction (XRD). XRD patterns revealed that the d-spacing of Na+ -MMT increase from 1.1 nm for Na+ -MMT to 2.18 nm for the OMMT, indicating intercalation of organic modifier into the interlayers of montmorillonites. Mechanical properties of IIR/OMMT nanocomposites were studied by means of tensile measurements. Tensile strengths of IIR/OMMT nanocomposites prepared from melt compounding and solution process were higher than those of IIR/Na+ -MMT nanocomposites and pristine IIR. When the solution process was used, IIR/OMMT nanocomposites provided further improvement in mechanical properties, as compared to those prepared from melt-compounding, indicating the better interaction between IIR and OMMT. PMID- 20352836 TI - Application of ordered nanoporous silica for removal of uranium ions from aqueous solutions. AB - Ordered nanoporous silica (MSU-H) with high surface area has been utilized as a solid substrate of a surface-modified hybrid sorbent for the application to the removal of U(VI). Carboxymethylated polyethyleneimine (CMPEI) with a strong complexing property has been introduced to the pore surface of MSU-H substrate. CMPEI-modified MSU-H (CMPEI/MSU-H) has been characterized by scanning electron microscopy and nitrogen sorption. In a kinetic experiment for 12.5 ppm U(VI) solution at pH 4.0, 99% U(VI) was removed from solution by the hybrid sorbent within less than 10 min, indicating that the sorption of U(VI) on the CMPEI/MSU-H proceeds very rapidly. It was evident that a U(VI) sorption capacity increased with pH in the range of 2.0 to 4.0. The CMPEI/MSU-H showed a high sorption capacity of 153 mg/g-sorbent at pH 4.0. In particular, the CMPEI/MSU-H showed a significantly high uranium loading stability. Only about 1% U(VI) was released out of CMPEI/MSU-H during 4 months, when the CMPEI/MSU-H was treated with polyacrylic acid. PMID- 20352837 TI - Direct synthesis of water-dispersible FePt nanoparticles capped with L-cysteine. AB - A direct synthetic route of FePt nanoparticles (NPs) has been developed. Reduction of platinum acethylacetonate (Pt(acac)2) and thermal decomposition of iron carbonyl (Fe(CO)5) in the presence of L-cysteine produced fcc FePt NPs with a mean diameter of 2.9 nm. Capping of the FePt NPs with L-cysteine is accomplished by a thiolate linkage between the amino acid and the NP surfaces, which renders them water-dispersible rather than in organic solvents. SQUID magnetization study demonstrated that the FePt NPs exhibited superparamagnetic behavior at 300 K. For the structural model of the FePt NPs, the Fe K-edge and Pt L(III)-edge XAFS results suggest that most of the Pt atoms are preferentially located in the core region, the Fe atoms are preferentially located in the shell region. PMID- 20352838 TI - MgO encapsulated mesoporous zeolite for the side chain alkylation of toluene with methanol. AB - Side chain alkylation of toluene with methanol was studied over mesoporous zeolite supported MgO catalysts. MgO were supported onto the carbon templated mesoporous silicalite-1 by direct synthesis route under microwave conditions. This direct synthesis route yields the majority of MgO highly dispersed into the mesopores of the silicalite-1 crystals. The vapor phase alkylation of toluene with methanol was performed over these catalysts under vapor phase conditions at atmospheric pressure. Mesoporous silicalite-1 supported MgO catalysts gave improved yields towards side chain alkylated products compared to the bulk MgO. The higher activity exhibited by 5% MgO supported on mesoporous silicalite compared to the one with 1% MgO can be attributed to the large number of weak basic sites observed from the CO2 TPD. PMID- 20352839 TI - Chemical and thermal stability of Pt nanocubes synthesized with various surface capping agents. AB - Pt nanocubes with a size of below 10 nm were synthesized by using various surface capping agents of polyvinylpyrrolidone (PVP), tetradecyltrimethylammonium bromide (TTAB), and oleylamine with high shape purity. TGA and XPS data revealed the amount and characteristics of the residual organic molecules on the surface of Pt nanocubes. Chemical and thermal stability of these nanoparticles were examined by observing the change of cubic shape upon heating under different chemical environments of N2, H2 and air. The shape change such as rounding of the vertexes or aggregation depended on the type of surface-capping agent and chemical environments. The cubic shape generally started to deform at 200 degrees C and the nanoparticles were mostly fused together at 300 degrees C. The thermal treatment under air produced more PtO layer on the surface with less shape deformation or aggregation when compared with H2 or N2 treatments. Among three surface-capping agents used in this study, oleylamine-capped Pt nanocubes show the highest shape stability with no shape change or aggregation even at 300 degrees C under air. PMID- 20352840 TI - Electronic structure and local atomic arrangement of transition metal ions in nanoporous iron-substituted nickel phosphates, VSB-1 and VSB-5. AB - The electronic structure and local atomic arrangement of transition metal ions in nanoporous iron-substituted nickel phosphates VSB-1 and VSB-5 have been investigated using X-ray absorption near-edge structure (XANES) spectroscopy at Fe K- and Ni K-edges. The Fe K-edge XANES study clearly demonstrated that substituted iron ions were stabilized in octahedral nickel sites of nanoporous nickel phosphate lattice. A comparison with several Fe-references revealed that the substituted irons have mixed Fe2+/Fe3+ oxidation state with the average valence of +2.8-3.0. According to the Ni K-edge XANES analysis, the aliovalent substitution of Ni2+ with Fe2+/Fe3+ induced a slight reduction of divalent nickel ions in VSB-5 to meet a charge balance. On the contrary, Fe substitution for the VSB-1 phase did not cause notable decrease in the oxidation state of nickel ions, which would be related either to the accompanying decrease of pentavalent phosphorus cations or to the increase of oxygen anions. In conclusion, the present findings clearly demonstrated that the nanoporous lattice of nickel phosphate can accommodate effectively iron ions in its octahedral nickel sites. PMID- 20352841 TI - Mechanism for enhancement of visible light response on nitrogen-doped TiO2 by modification with vanadium species. AB - Photocatalytic activities of nitrogen-doped TiO2 (N-TiO2) will remarkably increase by surface modification with vanadium (+V) species for the decomposition of volatile organic compounds (VOCs) in the presence of O2 under visible light irradiation. Study on the electron spin resonance (ESR) shows that the vanadium (+V) species interacted with N-TiO2 surface is photo-reduced to form vanadium (+IV) in vacuum or in the presence of hole scavengers under visible light irradiation, and subsequently, it is re-oxidized into vanadium (+V) by O2. Furthermore, the concentration of visible light induced holes (.N radicals) on V oxide/N-TiO2 is much higher than that on N-TiO2. Therefore, it is confirmed that the added vanadium species having oxidation states between +IV and +V that interact with surface N-TiO2 play significant roles as redox mediators in the effective charge separation of holes and electrons, which consequently brings about an enhancement of photocatalytic activity. PMID- 20352842 TI - Properties of Cu-based nanocomposites produced by mechanically-activated self propagating high-temperature synthesis and spark-plasma sintering. AB - One of the possible reasons for low conductivity of in-situ produced dispersion strengthened copper matrix composites may be the incompleteness of the reaction between the initial reactants that remain in a state of solid solutions in the copper matrix. We report in-situ synthesis of TiB2-Cu composites starting from the powder mixtures with the limited content of copper ensuring a high probability of contact between the particles of titanium and boron and, as a result, their full conversion into the TiB2 phase. The nanoparticles were formed in a self-propagating mode in the ball milled Ti-B-Cu powder mixture corresponding to 57 vol.% TiB2-Cu composition. Afterwards, the system was "diluted" with the required amount of the copper matrix using subsequent ball milling. Highly conductive 4.5 vol.% TiB2-Cu composites showing 82-87% IACS (International Annealed Copper Standard) conductivity were obtained by Spark Plasma Sintering (SPS) of the powders. PMID- 20352843 TI - Homogeneous dispersion of TiC nano particles in a cast carbon steel matrix. AB - Metal matrix nano-composites (MMNCs) (metal matrix with nano-sized ceramic particles) can be of great significance because of their high performance and thus it would be advantageous to produce as-cast bulk MMNCs. However, it is so difficult to disperse nano-sized ceramic particles uniformly in molten metal. In this study, carbon steel matrix composites with a homogeneous dispersion of TiC nano particles were fabricated by conventional liquid metal casting method. In order to get highly wettable nano-sized TiC ceramic particles, the micro-sized (approximately 10 m) TiC particles were first mechanically milled (MMed) by Cu in a high-energy ball mill machine (MMed TiC/Cu), and then mixed with Sn powders to obtain better wettability, as this lowered the surface tension of the carbon steel melt. According to OM images, an addition of MMed TiC/Cu-Sn mixed powders favorably disperses the TiC nano particles in the carbon steel matrix. SEM and EDS images revealed that spherical particles with several hundreds of nanometers were distributed uniformly in the carbon steel matrix. It was also found that the grain size refinement of the cast matrix is achieved remarkably when TiC nano particles were added due to the fact that TiC nano particles act as nucleation sites during the solidification process. PMID- 20352844 TI - Electrochromic properties of asymmetric 4,4'-bipyridinium nanocomposites with inorganic nanoparticles. AB - Asymmetric mono cationic 4,4'-bipyridiniums, 1-butyl-4,4'-bipyridinium bromide (BUBP) and 1-methyl-4,4'-bipyridinium iodide (MEBP) showed electrochromic properties from blue to transparent yellow. The electrochromic bipyridiniums, BUBP and MEBP, were introduced to solid state electrochromic cells by using a solution of the bipyridinium, TiO2, and polymer electrolyte composite. The 4,4' bipyridinium derivatives was attached to TiO2 nanoparticles and decreased aggregation of TiO2 to afford EC dye-TiO2 nanoparticles with average diameter smaller than 20 nm, as determined by FE-SEM. An all solid state electrochromic cells prepared from the dye-TiO2 nanoparticles showed improved electrochromic response compared to that without TiO2. Thus the cell from the BUBP- TiO2 nanoparticles responded to a step potential of +/-2 V within 7 sec with coloration efficiency of 117. The redox cyclability of the bipyridinium-TiO2 nanoparticles cell was longer than that of the TiO2 free cells. The enhanced properties were attributed to the conductivity and the large surface area of TiO2 nanoparticles. PMID- 20352846 TI - Ethylene vinyl acetate copolymer/multi-walled carbon nanotube nanocomposites. AB - In this study relatively large amount of ethylene-vinyl acetate copolymer (EVA) (130 g) was melt-mixed with multi walled carbon nanotube (MWCNT) and the effect of mixing time and rotor speed on electrical properties were investigated. Also, to investigate the relationship between the degree of dispersion of MWCNT and conductivity, the dispersion of MWCNT was examined using SEM and TEM. At shorter mixing time (15 min), increased rotor speed produces improved conductivity, whereas at longer mixing time (25 min and 35 min) increased rotor speed leads to enhanced breakage of the MWCNT and decrease of conductivity even though the dispersion of MWCNT is improved. Therefore to obtain the best conductivity, optimal shear rate and mixing time should be chosen. PMID- 20352845 TI - Preparation and characterization of Rh catalyst supported on nanoporous alumina for the ethylene hydroformylation. AB - Nanoporous gamma-aluminas were prepared by a sol-gel method with and without surfactant, and characterized by nitrogen adsorption-desorption, transmission electron microscopy (TEM), X-ray diffraction (XRD) and temperature programmed reduction (TPR). The resulting materials were applied to Rh catalyst supports for the ethylene hydroformylation. The ordered nanoporous alumina (A-1) which was prepared using surfactant, showed well-developed pore structures with high surface area. Rh catalyst supported on A-1 alumina (Rh/A-1) exhibited higher catalytic activity in the ethylene hydroformylation than other Rh catalysts. It is believed that the high catalytic performance of Rh/A-1 resulted from the well developed pore structure with high surface area of ordered nanoporous A-1 and consequently finely dispersed Rh particle on the surface of gamma-alumina support. PMID- 20352847 TI - Confinement effects of P3HT in nanochannels and their implications for bulk heterojunction solar cells. AB - We studied the properties of regioregular P3HT conducting polymers with three different molecular weights infiltrated into the pores of mesoporous titania thin films. The titania thin films, prepared by self-organization of titania species with a non-ionic triblock copolymer F127 followed by calcination to remove organics, have arrays of 7 nm vertical nanochannels. The UV-Vis spectra of the P3HT-titania nanocomposite films revealed that the interstrand interactions between P3HT chains were weakened by the infiltration. Such an effect increases as the molecular weight of P3HT increases and as the infiltration temperature increases. Consequently, the efficiency of the solar cells, assembled by using the P3HT infiltrated mesoporous titania thin films, was the highest with the smallest P3HT, contrary to the generally accepted practice of using high molecular weight P3HT for forming bulk heterojunction solar cells. PMID- 20352848 TI - Novel fabrication of polyaniline particles wrapped by exfoliated clay sheets and their electrorheology. AB - Taking into account of unique merits of conducting polymer/inorganic nanocomposites which play a positive effect in enhancing electrorheological (ER) performances, we adopted exfoliated clay sheet as a stabilizer to fabricate novel nano-scaled polyaniline (PANI) granules (PANI/clay) via pickering inverse emulsion polymerization in this study. Successfully synthesized PANI nano-spheres which were initialized by oil-soluble benzoyl peroxide possessed polydispersed size distribution. These armed PANI nanoparticles, of which the surface is compactly wrapped by clay sheets, are observed, as confirmed by SEM and TEM images. Some nano-scaled particles even possess irregular shape with sharp angle because clay plates are difficult to be bended to follow the spherical trace due to the extremely small size of PANI granules. The extent of exfoliation of Clay sheets covered on the surface of PANI particles were characterized by XRD pattern which did not indicate any obvious sharp peak, demonstrating the nearly completely exfoliated clay layers. TGA spectra also gave some additional information on thermal stability and mass composition. At last, an ER fluid was prepared by dispersing PANI/clay nanoparticles in silicone oil and the ER performances were investigated via a rotational test. PMID- 20352849 TI - Synthesis of functionalized mesoporous material with various organo-silanes. AB - Two kinds of ordered mesoporous silicas, SBA-15 and MSU-H, have been synthesized and functionalized by direct and post synthesis method to widen their various application possibilities. In this study, phenyltrimethoxysilane (PTMS), methacryloxy-methyltrimethoxysilane (MAMTMS), 2-(3,4 epoxycyclohexyl)ethyltrimethoxysilane (ECETMS), and N(beta-aminoethyl)-gamma aminopropylmethyldimethoxysilane (AEAPMDMS) were used as a silane precursor for the functionalization. The post synthesis was more effective method to sustain ordered pore structure than the direct synthesis method under our experimental conditions. The surface area and pore size of mesoporous silica SBA-15 and MSU-H decreased through the functionalization process. FT-IR and XPS results confirmed the functionalized silane existence in the SBA-15/MAMTMS. These functional groups (vinyl, epoxide, and amine group) could be useful for various applications such as a linker of functional organic materials or active metal for heterogeneous catalysts. As a practical instance, rhodium immobilized on the aminated SBA-15 was investigated as a 1-octene hydroformylation. PMID- 20352851 TI - Microwave-assisted solvothermal synthesis of CuInSe2 chalcopyrites. AB - Chalcopyrite, CuInSe2 was prepared by a fast microwave-assisted solvothermal synthesis. The influence of reaction temperature, concentrations of the constituents, types of copper salts and added solvent on the morphology and crystallinity of the chalcopyrite has been investigated and also the optimized parameters are presented. The optimum crystallinity was obtained at 180 degrees C reaction temperature with 0.02 M of copper ion concentration. Interestingly, when the copper acetate was used as a copper source, particle size of chalcopyrite was dramatically reduced. Moreover, the synthesis at 1L scale of the reactants gave the particle size of 20 nm for CuInSe2 which is smaller than that of small scale synthesis (23-35 nm). XRD, SEM and Raman Spectroscopy techniques are used for characterization and evaluation of the morphology of the chalcopyrite. PMID- 20352850 TI - Photocatalytic degradation of procion blue dye in aqueous solution by a TiO2 carbon nano-composite. AB - A nano-composite consisting of TiO2-CNT was prepared via the sol-gel technique by using titanium n-butoxide along with carbon nano-tubes (CNTs) followed by calcination at 450 degrees C. Spectral analysis reveals that the TiO2 formed was present on the carbon in anatase form. The effect of adsorption was investigated in an aqueous solution of procion blue dye in a darkroom and the photochemical reaction in aqueous suspensions of titania composite under UV illumination. The reaction was studied by monitoring the discoloration of dye via employing a UV Visible spectrophotometeric technique as a function of irradiation time. The composite catalyst was found to be efficient in the photodegradation of the dye. PMID- 20352852 TI - Synthesis of nanocrystalline bismuth and its application to the detection of trace metals. AB - Surface modified carbon strip electrode with Bi nanopowder was suggested for a simultaneous analysis of Zn, Cd, and Pb ions by a square wave anodic stripping voltammetry, and the influence of the modifying Bi mass and particle size on the trace metal response was investigated. The Bi nanopowders with various particle size distributions were synthesized by an optimization of the gas condensation condition, in which a refractory crucible was applied for the evaporation of volatile Bi, and then immobilized on the surface of a working electrode. The result of the stripping measurements shows that when the modifying mass and the particle size of the Bi powder were in the range of 2 to 5 microg/cm2 and less than 300 nm, respectively, a well-developed and reproducible stripping response was obtained. The proposed "mercury-free" carbon strip electrode, modified with Bi nanopowder, is conveniently usable and directly applicable to a trace metal analysis without a pre-deposition of Bi and complicated surface polishing steps. PMID- 20352853 TI - Incorporation of arene metal carbonyl complexes within inorganic-organic hybrid mesoporous materials by CVD method. AB - Simple chemical vapor deposition (CVD) of M(CO), (M = Cr, Mo, W) onto phenylene- and biphenylene-bridged organosilica mesoporous materials (HMM-ph, HMM-biph) led to the efficient formation of C6H4M(CO)3 and (C6H4)2M(CO)3 complexes, respectively, which are directly fixed and incorporated within the framework structure of HMM-ph and HMM-biph having molecular-scale periodicity in the pore walls. FT-IR investigations revealed that thus formed C6H4M(CO), or (C6H4)2M(CO)3 complexes are thermally stable even under thermovacuum treatment at 473 K. PMID- 20352854 TI - High temperature oxidation of a nanolayer laminated (Cr0.95Ti0.05)2AlC compound in air. AB - High-purity, dense nano-laminated (Cr0.95Ti0.05)2AlC compounds were synthesized via a powder metallurgical route. Their oxidation characteristics were investigated by exposing them to temperatures between 900 and 1200 degrees C in air. The alloying Ti in the Cr layer of Cr2AlC did not significantly change the crystal structure and microstructure of Cr2AlC. But, it increased the oxidation rate of the Cr,AlC. The scale morphology of the (Cr0.95Ti0.05)2AlC was basically similar to that of the pure Cr2AlC. The main difference was that the (Cr0.95Ti0.05)2AlC contained oxide nodules. These formed because the titanium oxidized to TiO2, making the Cr2AlC susceptible to nodular oxidation. However, alpha-Al2O3 was still the major oxidation product in both the (Cr0.95Ti0.05)2AlC and pure Cr2AlC. PMID- 20352855 TI - Electrochemical behaviors of polymer composite electrolytes containing functionalized nanosize clays. AB - Functionalized nanosize clay effect on the poly(ethylene oxide) (PEO)-based polymer composite electrolytes (PCE) were prepared and studied. In order to understand the effects of organic-functionalized montmorillonite (OMMT) on the ionic conductivity, microstructure and electrochemical property were investigated. XRD results revealed that the PCE containing MMT-20A showed interlayer spacing length, 2.55 nm, while the PCE containing Na-MMT showed the value, 1.16 nm. By changing the OMMT species, the interlayer spacings were controlled. The XRD and thermal analysis results indicated that the PCE showed the reduced crystallinity by introduction of OMMT fillers. PCE containing MMT-20A showed the triple higher conductivity, 6.1 x 10(-4) S/cm, than PCE containing Na MMT. This indicated that the improved ion conductivity was dependent on the reduced crystallinity that was correlated with the d-spacing of MMT. PMID- 20352856 TI - Fabrication of mesoporous carbons with rod and winding road like morphology using NbSBA-15 templates. AB - Here we demonstrate for the first time the fabrication hexagonally ordered mesoporous carbon materials with different morphology and pore diameters using NbSBA-15 mesoporous silica template with different niobium content. The materials were characterized by several characterization techniques such as XRD, HRSEM, HRTEM, elemental mapping, ICP-AES, and EDS analysis. We also demonstrate that the morphology of the materials can be controlled by simply tuning the morphology of the parent NbSBA-15 template, whose morphology can be tuned by adjusting the loading of niobium in the framework wall structure of SBA-15. Nitrogen adsorption results reveal that the textural parameters of the mesoporous carbon materials prepared from NbSBA-15 are much better than those prepared with pristine SBA-15 template, and vary with the amount niobium present in the template. It was also found that the pore diameter of the NbMC-X increases with decreasing the amount of niobium in the framework wall structure of the template. The morphology and the topology of the materials were observed by HRSEM and HRTEM, respectively. The materials with rod and semi-spherical or winding road like morphology can be obtained using NbSBA-15 materials with different Nb content. It was found that the usage of NbSBA-15 as templates for the fabrication of mesoporous carbon materials can also allow us to decorate the pore channels of the materials with either niobium oxide or niobium silicate nanoparticles which are expected to show high performance when used in redox catalysis, and the biomolecule adsorption as the niobium has the strong tendency to adsorb the protein molecules. PMID- 20352857 TI - Crystallization of amorphous Fe90Zr10 under ball milling. AB - The present study deals with structural transformations induced by high-energy ball-milling of an amorphous Fe90Zr10 alloy prepared by melt-spinning. The amorphous melt-spun ribbons were found to undergo crystallization into BCC alpha Fe(Zr) nanocrystallites under high-energy ball milling. The decomposition degree of the amorphous phase increased with increasing milling time and intensity. Our results suggest that the observed crystallization is a deformation-induced process rather than a thermally induced one. PMID- 20352858 TI - Improvement of photovoltaic efficiency of dye-sensitized solar cell by introducing highly transparent nanoporous TiO2 buffer layer. AB - 13 nm-sized highly-dispersible TiO2 nanoparticle was synthesized by solvothermal reaction of titanium isopropoxide in a basic condition with tetrabutylammonium hydroxide (TBAH). The prepared TiO2 nanoparticle was applied to fabrication of the transparent nanoporous TiO2 layer with 1.2 microm-thickness. By introducing this buffer layer between FTO and main TiO2 layer in the dye-sensitized solar cell (DSSC), the photovoltaic conversion efficiency was improved from 5.92% to 7.13%. Due to the excellent antireflective role of nanoporous TiO2 buffer layer, the transmittance of FTO glass was increased by 9.2%, and this seemed to be one of the major factors in enhancing photovoltaic conversion efficiency. Moreover, the presence of nanoporous TiO2 buffer layer induces excellent adhesion between FTO and main TiO2 layer, as well as it suppresses the back reaction by blocking direct contact between I3- and FTO electrode. PMID- 20352859 TI - Drug release behavior from nanoporous anodic aluminum oxide. AB - In this study, we developed a new drug delivery system using anodic oxidation. The growth of a porous oxide layer on aluminum under anodic bias in various electrolytes has been studied for more than 40 years. Anodic Aluminum Oxide (AAO) has many uniform nanopores on its surface. This nanoporous surface can be used for drug storage. The effects of the diameter and depth of the AAO on the release characteristics of a drug were investigated. Paclitaxel was used for the drug loading and release test. Paclitaxel was loaded on the inside of the AAO by ultrasonication. The amount of the drug released from the AAO was analyzed by high performance liquid chromatography (HPLC). The pore size did not affect the drug release behavior. However, the depth of the pores had a significant influence on the release rate of the drug. PMID- 20352860 TI - Synthesis and characterization of WS2 nanoparticles by chemical vapor condensation. AB - Nano-sized WS2 based powders were synthesized by chemical vapor condensation (CVC) process using tungsten carbonyl (W(CO)6) as precursor and vaporized sulphur. Prior to WS2 nanopowders synthesis, pure tungsten nanopowders were produced by chemical vapor condensation to define the optimum synthesis parameters, which were then successfully applied to synthesize tungsten disulphide. The influence of experimental parameters on phase and chemical composition as well as mean size of the particles in order to produce pure tungsten and WS2 nanopowders was studied. Structure, phase composition and particles size of WS2 nanoparticles were precisely characterized by means of XRD, FESEM and TEM. PMID- 20352862 TI - Electrochemical fabrication of Pt-Au-WO3 electrodes for direct methanol fuel cell. AB - Pt-Au-WO3 ternary electrodes with various compositions were synthesized by electrochemical method from a mixture of H2PtCl6 aqueous solution, HAuCl4 aqueous solution, and W-peroxo complex. Their electrocatalytic activities for methanol oxidation were investigated. Film composition was controlled by varying the concentration of each component in electrolytes. Morphology and compositional analyses of the synthesized films were performed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The catalytic activity and initial behavior of current density for methanol oxidation of the synthesized films were measured using cyclic voltammetry (CV) and chronoamperometry (CA) in a mixture of 0.5 M H2SO4 and 0.5 M CH3OH solution. Electrocatalytic activity for CO oxidation was also evaluated in 0.5 M H2SO4 solution. The activities of various electrodes for methanol oxidation were found to be strongly dependent on film composition. Pt-Au-WO3 electrodes exhibited higher activity for CO oxidation than pure Pt. The addition of proper amount of Au and WO3 significantly improved catalytic activity for methanol oxidation. PMID- 20352861 TI - Application of hierarchical MFI zeolite for the catalytic pyrolysis of Japanese larch. AB - The catalytic pyrolysis of Japanese larch was carried out over a hierarchical MFI zeolite (Meso MFI C16). The zeolite was synthesized using an amphiphilic organosilane as a mesopore-directing agent, and its catalytic activity was compared with that of the conventional HZSM-5 and the mesoporous material from HZSM-5 (MMZ(ZSM-5)). The effect of the hierarchical MFI zeolite on the product distribution and chemical composition of the bio-oil was also examined. The hierarchical MFI zeolite exhibited the highest activity in deoxygenation and aromatization during the catalytic pyrolysis of Japanese larch. In particular, it showed high selectivity for valuable aromatics, such as benzene, toluene, and xylenes (BTX), even though it decreased the organic fraction of bio-oil. Its higher mesoporosity resulted, however, in an increase in the coke amount and in undesirable products, such as polycyclic aromatic hydrocarbons (PAHs). PMID- 20352863 TI - Fabrication of alumina-based metal nanocomposites by pressureless sintering and their mechanical properties. AB - The processing conditions to prepare nano-sized Cu and Mo dispersed Al2O3 (Al2O3/Cu and Al2O3/Mo) composites by pressureless sintering were explored. The composite powders of Al2O3/Cu and Al2O3/Mo were obtained by the hydrogen reduction of Al2O3/CuO and Al2O3/MoO3 powder mixtures and consolidated by pressureless sintering using infrared heating furnace with a heating rate of 200 degrees C/min. SEM and TEM analyses for the composite showed that the nano-sized metal particles were well distributed and situated on the grain boundaries of the Al2O3 matrix. The nanocomposites, sintered at 1300 to 1500 degrees C for 4 min, showed the relative density of above 90%. Maximum hardness of 16.1 GPa was obtained in Al2O3/Cu nanocomposites with sintering additive of 1 wt% MgO. The sintered nanocomposites exhibited the enhanced fracture toughness of above 4.5 MPa x m(1/2), compared with monolithic Al2O3. The mechanical properties were discussed in terms of observed microstructural characteristics. PMID- 20352864 TI - Control of mode of crystal networking during monolayer assembly of microcrystals on water. AB - A series of hydrocarbon (HC)-coated cubic zeolite microcrystals (1.7 microm) was prepared. The HCs were n-octyl, n-dodecyl, methyl n-undecanoate, n-octadecyl, and n-heptadecafluorodecyl. The measured water contact angles (theta) of the corresponding HC-coated glass plates were 64, 77, 82, 102, and 105 degrees, respectively, indicating that the hydrophobicity of the surface-tethered hydrophobic chain (HC) increased in the above order. The HC-coated zeolite microcrystals readily formed closely packed monolayers at the air-water interface through interdigitation of surface-tethered HCs, and on glass plates after transferring onto glass plates by dip coating. Interestingly, while the mode of networking was face-to-face (FTF) contacting with n-octyl or n-dodecyl (theta < or =77 degrees) as HC, it changed to edge-to-edge (ETE) contacting mode with n octadecyl or n-heptadecafluorodecyl (theta > or = 102 degrees) as HC. With methyl n-undecanoate (theta = 82 degrees) as HC, both modes appeared in the monolayers, with about equal populations. The resulting monolayers of cubic zeolite microcrystals with their three-fold axes oriented perpendicular to substrates would be useful for application of the zeolite monolayers for advanced materials. PMID- 20352865 TI - CO oxidation of Pt nanostructures supported by TiO2/Ti. AB - This study examined the CO oxidation reactivity of Pt deposited on TiO2. The Pt catalysts were prepared by the evaporation of Pt on Ti foils covered with TiO2, and their surface structures were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Separate Pt nanoparticles could be observed with lower amounts of deposited Pt (<2 nm). With increasing Pt thickness, these Pt nanoparticles appeared to agglomerate into more complicated nanostructures. When approximately 5 nm of Pt was deposited, the TiO2 surface was almost completely covered by Pt. Additional deposition of Pt on these complete Pt layers resulted in the deposition of small nanoparticles (approximately 5 nm) on top of the Pt underlayer. The CO oxidation reactivity at 160 degrees C, normalized with respect to the Pt thickness, initially decreased with increasing amount of Pt. This was attributed mainly to the decrease in the surface-to-volume ratio. However, the reactivity increased when the amount of Pt exceeded 5 nm, which can be rationalized in part by the unique structural properties of Pt-films according to SEM imaging. We also suggest that a stronger influence of the metal support interactions at lower Pt coverages results in reduced catalytic activity. PMID- 20352866 TI - One-step silica coating of cetyltrimethyl ammonium bromide-stabilized alpha Fe2O3. AB - The alpha-Fe2O3 nanoparticles were coated with silica using intermediated surfactant such as cetyltrimethyl ammonium bromide (CTAB). After the formation of a thin intermediate layer in basic solution without any purification, TEOS was added directly to the solution for further silica growing. Silica thickness can be controlled through the various synthetic conditions (5 to 50 nm). The synthesized powder was characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and UV-visible spectroscopy. XRD and UV visible spectroscopy of silica coated alpha-Fe2O3 is preserved constant after coating silica, suggesting that the SiO2 layers can be regarded as protecting layers without destroying the properties of the alpha-Fe2O3 nanoparticles. PMID- 20352867 TI - Anisotropic shape evolution of large-size Cu nanocrystals prepared in nonionic microemulsion media. AB - We report the anisotropic shape evolution of colloidal copper nanocrystals (Cu NCs) in nonionic microemulsion media by adopting tetraethylammonium hydroxide as a reactant and capping agent in water phase. Relatively large-size Cu NCs were synthesized to confine the growth of Cu NCs below 100 nm. TEM images showed the triangular and hexagonal morphologies of Cu NCs ranging over 55-70 nm after 28 h, while they showed the spherical NCs dominantly under higher concentration of a reducing agent. The surface plasmon resonance (SPR) absorption band of anisotropic Cu NCs was centered at 571 nm with signal enhancement over time. The formation kinetics revealed that the gradual conversion of the Cu seeds into larger NCs during 28 h at room temperature. The NCs were characterized to be Cu rather than CuO or Cu2O by electron diffraction patterns, exhibiting relevant d spacing figures consistent with the bulk Cu crystal. PMID- 20352868 TI - Colorless polyimide/organoclay nanocomposite substrates for flexible organic light-emitting devices. AB - We report the preparation and application of indium tin oxide (ITO) coated fluorine-containing polyimide/organoclay nanocomposite substrate. Fluorine containing polyimide/organoclay nanocomposite films were prepared through thermal imidization of poly(amic acid)/organoclay mixture films, whilst on which ITO thin films were coated on the films using a radio-frequency planar magnetron sputtering by varying the substrate temperature and the ITO thickness. Finally the ITO coated fluorine-containing polyimide/organoclay nanocomposite substrate was employed to make flexible organic light-emitting devices (OLED). Results showed that the lower sheet resistance was achieved when the substrate temperature was high and the ITO film was thick even though the optical transmittance was slightly lowered as the thickness increased. approximately 10 nm width ITO nanorods were found for all samples but the size of clusters with the nanorods was generally increased with the substrate temperature and the thickness. The flexible OLED made using the present substrate was quite stable even when the device was extremely bended. PMID- 20352869 TI - Mechanism for alpha-MnO2 nanowire-induced cytotoxicity in Hela cells. AB - Alpha-Manganese dioxide (alpha-MnO2) nanowires are used as electrode materials to significantly enhance the performance of lithium batteries. In this study, we investigate the nanotoxicity of alpha-MnO2 nanowires toward Hela cells. The alpha MnO2 nanowires, which were successfully synthesized using the hydrothermal approach, can induce cytotoxicity dose-dependently in Hela cells. The accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are also observed in the nanowire-treated cells. In addition, comet assays and cell nucleus morphology show that both DNA damage and cell apoptosis occur in the nanowires exposure group. Based on these results, a mechanism for alpha-MnO2 nanowire-induced cytotoxicity in Hela cells, which involves the accumulation of ROS, formation of oxidative stress, DNA oxidative damage and cell apoptosis, is proposed. This investigation may provide a fundamental insight to understand the nanotoxicity of wire-shaped nanomaterials. PMID- 20352870 TI - Electromechanical characteristics of ZnO:Al nanorods. AB - In this study, we explore the effect of aluminum doping on the mechanical, piezoelectric, and semiconductive properties of zinc oxide (ZnO) nanorods using scanning probe microscopy. The results show that the size of ZnO:Al nanorods can be changed by tuning the dopant concentrations during nanorod growth. The average surface potentials of the samples were -42.2-34.4 mV. Single nanorod bending generation output surface potentials were 0.05-0.08 V. The power density per unit substrate area was 0.72 nW/mm(-2) for a device outputting ultrasonic wavelengths. PMID- 20352871 TI - Characterization of a self-assembled monolayer based on a calix[4]crown-5 derivate: fabrication of a chemical sensor sensitive to calcium. AB - The synthesis and self-assembled monolayer (SAM) formation of a calix[4]crown-5 derivative are reported. Several techniques, including electrochemistry, atomic force microscopy (AFM), Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and contact angle measurements have been applied to characterise the monolayer film designed for chemical sensor applications. The recognition properties of this SAM for metal cations has been investigated using impedance spectroscopy (IS) showing an electrochemical response proportional to calcium ion concentration in the range from 10(-7) M to 10(-2) M. This response is related to microscopic changes at the gold surface induced by selective binding by the immobilised calixarene. PMID- 20352872 TI - Synthesis of h-AIN nanowires via carbothermal reduction and nitridation method using acetylene black. AB - Using acetylene black as an assistant reagent in the ammonia atmosphere, one dimensional (1D) hexagonal single crystalline aluminum nitride (AIN) nanowires were successfully synthesized via carbothermal reduction and nitridation method. With smooth surface and uniform diameter, the wool-like product of AIN nanowires grow along [001] direction and are 80-120 nm in diameter and several tens micrometers in length. According to thermodynamic and kinetic analysis, AI2O3 initially was reduced to a volatile suboxide gas Al2O at 1800 degrees C. Then gaseous Al2O was transported by N2/NH3 mixtures to about 1200 degrees C, where 1D AIN nanowires formed by the reaction of Al2O gas, graphite and NH3. Due to high surface area, small particle size and amorphous structure, acetylene black maybe possess more active sites and more effective contact area, which benefits the first step reaction. The electrostatic polar charge model and crystallographic characteristics are employed to explain the growth mechanism of AIN nanowires. To our knowledge, acetylene black is the first time to be used for synthesizing 1D AIN nanostructures via carbothermal reduction and nitridation method, which would be an efficient, economical assistant reagent for fabricating nitride nanostructures. PMID- 20352873 TI - Anisotropic growth and formation mechanism investigation of 1D ZnO nanorods in spin-coating sol-gel process. AB - ZnO nanorods are fabricated on glass substrate by spin-coating sol-gel process using non-basic aged solution and annealing. Sample solutions reserved in room temperature for different time (one day, one month, two months and four months) are prepared for the experiment. The morphology study indicates that the aging time has direct influence on the final products. This is verified by the Transmission Electron Microscopy and Photon Correlation Spectroscopy study. Small crystalline nanoparticles would gradually nucleate and aggregate in the sol during the aging process. They act as nucleation site for the secondary crystal growth into nanorods during anneal. Both the size of crystalline particles in the sol and the size of nanorods will grow bigger as the aging time increases. The products' structure and optical property are further studied by X-ray diffraction spectroscopy, Photoluminescence and Raman spectroscopy. This work also helps to further clarify the formation mechanism of ZnO nanorods by solution-based method. PMID- 20352874 TI - Field effect properties of phosphorus doped CdS single-crystal nanoribbon via co thermal-evaporation. AB - High quality Phosphorus doped (P-doped) CdS nanoribbons (NRs) were synthesized with different doping levels by co-thermal-evaporation. The field-effect transistors based on as-synthesized nanoribbons were fabricated successfully too. The as-synthesized Phosphorus doped CdS nanoribbons are wurtzite structure and grow along the [110] orientation. The XRD patterns of doped CdS nanoribbons show obviously shifting to left with the increasing of a and c lattice parameters when percent of dopant is up to 3.18%. The contact of Phosphorus-doped CdS nanoribbons with the electrodes was found to be ohmic contacts, which present the approximate linear relations between source-drain current versus voltage measured by two terminal measurements. It is noted that the characterization of Vg-dependent current versus bias voltage curves demonstrates the n-type semiconductors of as prepared CdS nanoribbons due to self-compensation effects. The electron mobility of two levels P-doped CdS nanoribbons is calculated to be 175 cm2/Ns and 1.58 cm2/Vs, respectively. The conductance of the higher doping level is three magnitudes larger than that of the lower one nearly. Moreover, the increasing of electronic carriers concentration make the gap between the Fermi level and the conduction band minimum is lower comparing to the intrinsic CdS Nanoribbons. PMID- 20352875 TI - Grating-assisted spectrally-narrowed emissions from an organic slab crystal excited with a mercury lamp. AB - We report spectrally-narrowed emissions that take place from an organic semiconductor slab crystal of 2,5-bis(4-biphenylyl)thiophene (BP1T) under a low excitation-intensity regime. These emissions are caused with a mercury lamp that operates on a household power supply with an electric current approximately 1 A. The BP1T slab crystal is equipped with a distributed Bragg reflector. To complete this structure the slab crystal is attached to a diffraction grating that is engraved on a surface of a quartz glass substrate. The diffraction gratings have precisely been formed using a focused ion beam with a nanometer-defined precision. The spectral narrowing accompanied by the emission intensity increment is related to the strong mode-coupling between the forward electromagnetic wave and the backward (i.e., reflected) wave within the grating zone. Using a laser we also carried out the emission measurements on the BP1T crystals under a high excitation-intensity regime. The emissions are characterized as the longitudinal multimode laser oscillation, enabling us to determine the group refractive index of 4.56 for the BP1T slab crystal. Under both the low and high excitation intensity regimes excitons are dominant species of the emission. Their participation in the spectrally-narrowed emissions is briefly discussed. PMID- 20352876 TI - Microwave irradiation of pristine multi-walled carbon nanotubes in vacuum. AB - The goal of the present paper was to study the behavior of commercially available pristine multi-walled carbon nanotubes (MWNTs) under microwave irradiation (exposures up to 200 s) in vacuum, by means of several experimental techniques. An intense glow and heating of the nanotube samples were observed. Raman spectra, scanning electron microscopy (SEM) and scanning tunneling microscopy (STM) images of the processed nanotubes did not show considerable changes as compared to those for pristine MWNTs. Closer structural investigation by means of conventional and high-resolution transmission electron microscopy (TEM and HRTEM, respectively) revealed an increase in the occurrence of open nanotube ends, whereas the sidewalls remained generally unchanged. The possibility of increase in the number of entry ports for gases was verified by employing temperature programmed desorption experiments with mass spectrometric detection (TPD-MS) with pristine and microwave-irradiated MWNTs exposed to atmosphere. The overall adsorption capacity did not change, whereas the rate of adsorption increased roughly by twice for the nanotubes irradiated for 200 s as compared to pristine MWNTs, which is consistent with selective opening of the nanotube ends. PMID- 20352877 TI - Nanomachining of permalloy for fabricating nanoscale ferromagnetic structures using atomic force microscopy. AB - It is well-known that the tip of an Atomic Force Microscope (AFM) can act as a cutting tool for machining various types of materials. In this article, AFM machining experiments have been conducted to investigate the machining characteristics of a nickel-iron thin film material. The influences of the machining parameters on the resulting machined geometries and surfaces are specifically investigated. The machining parameters considered include the normal applied force, number of machining cycles, machining speed, and machining direction. To demonstrate its versatility, the machining technique developed has been applied for fabricating a NiFe based nanostructure required by many ferromagnetic devices. All results indicate that the machined groove size can be well correlated with and precisely controlled by the applied force and the machining cyclic number. The AFM machining technique is indeed simple and predictable for machining nanostructures with specified dimension and controllable precision. PMID- 20352878 TI - Single-photon and two-photon cellular imagings of gold nanorods and dyes. AB - A method to obtain the expressions of gold nanorods (GNRs) and dye molecules simultaneously is proposed for the single-photon and two-photon cellular imagings by using laser scanning confocal microscopy. For our experiment, GNRs with an average aspect ratio of 2.14 were synthesized using electrochemical method, and the peak of absorption spectrum of GNRs is at 600 nm. The human breast cancer cell lines (MDA-MB-435) were studied by incubating them with GNRs for 20 hours and then staining their nuclei with dye molecules-Prodium Iodide (PI). For the single-photon imaging, different CW lasers (458, 488, 514, 561, and 633 nm) were used individually to irradiate the samples. By adjusting the ranges of two bandpass filters for the detection, the scattered light from the GNRs due to surface plasmon resonance (SPR) and the fluorescence from PI can be induced simultaneously but be detected separately without crosstalk. Furthermore, the two cellular images can be merged together to become a composited cellular image. The TEM image shows that several clusters of GNRs internalized by the vesicles are distributed sparsely inside the cytoplasm, due to the endocytosis of the cells. The aggregation of GNRs causes SPR band broadened. Therefore strong scattered light from GNRs can almost be induced by different-wavelength lasers irradiating. However, the expression of PI can only be detected by the exciting lasers with a wavelength shorter than 600 nm. For the two-photon imaging of these cells internalizing GNRs, an ultrafast Ti:Sapphire IR-laser (800 nm) was used for irradiating the sample, and two bandpass filters were also adjusted to distinguish the photoluminescence of GNRs from the fluorescence of PI. PMID- 20352879 TI - The fluorinated (10, 0) boron nitride nanotube: a computational nuclear magnetic resonance and nuclear quadrupole resonance study. AB - Quantum chemical calculations at the level of density functional theory (DFT) were carried out to investigate the influence of fluorination boron and nitrogen nuclear magnetic resonance (NMR) and also nuclear quadrupole resonance (NQR) parameters in the (10, 0) single-wall boron nitride nanotube (SWBNNT). To achieve this aim three models of (10, 0) boron nitride nanotubes (BNNTs), raw and two F attached (exohedral and endohedral) derivatives were studied. The results of calculations showed that while the boron atom chemically bonded to F atom has the largest chemical shielding isotropy (CSI); it has the smallest quadrupole coupling constant (CQ) value among the other boron nuclei. PMID- 20352880 TI - Detection of multiple SNPs in numerous samples with polyacrylamide gel-based microarray. AB - Previously we have developed polyacrylamide gel-based DNA microarray to genotype single nucleotide polymorphism (SNP) in a large number of samples, which has been proved as a simple and robust platform for high-throughput SNP screening. Here we improved this method to detect multiple SNPs by introducing multiplex polymerase chain reaction (multiplex-PCR) and immobilizing the products of multiplex-PCR to fabricate gel-based microarray and applying universal dual-color detectors in hybridization. In this report, five SNPs (rs191296, rs2280073, rs17599165, rs17599416 and rs7660336) of GABRA4 gene were chosen and successfully analyzed with the improved platform. Our experiment demonstrated that 3-dimentional polyacrylamide gel-based microarray of multiplex-PCR products make the platform for multiple SNPs genotyping becoming more labor-saving and time-saving. Appling the universal dual-color fluorescent detectors can reduce the cost over two thirds for multiple SNPs analysis. It is concluded that the multiplex-PCR combined with the gel-based microarray hybridized with universal dual-color fluorescent detectors is efficient, rapid and simple for the detection of a single nucleotide mismatch, and may be very competitive in the efficiency, fidelity and cost for constructing DNA microarrays. PMID- 20352881 TI - Preparation and characterization of CdSe/ZnS quantum dots encapsulated in poly(ethylene glycol)-b-poly(D,L-lactide) micelle nanoparticles. AB - The final goal of this study is to develop multi-functional organic/inorganic hybrid nanoparticles, which can be utilized as biomedical imaging probes and drug delivery carriers. As an initial step toward this goal, we encapsulated CdSe/ZnS quantum dots (QDs) into poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) micelles using a solid dispersion method. The size and fluorescent intensity of QDs encapsulated in PEG-PLA micelles depended on the amount of incorporated QDs. For example, when the amount of QDs increased from 0.1 to 1.0 microg, the mean diameter increased from 24.2 +/- 6.0 to 211.2 +/- 6.5 nm and the fluorescent intensity changed from 10.2 +/- 1.0 to 469.9 +/- 15.6 (RFU). Stability studies showed that the size and zeta-potential (ZP) of QDs encapsulated in PEG-PLA micelles (QEMs) did not change significantly in response to a change in pH conditions or under a 10% serum condition. We also tested the cytotoxicity and cellular uptake of the QEMs. The viability of HeLa cells treated with micelles for 24 h was 80-100% in various concentration ranges of micelles. Confocal laser scanning microscopic images showed that the QEMs penetrated into the cells, particularly into the cytosolic compartments. Our results suggest that the QEMs may be a promising multi-functional nanocarrier for biomedical imaging and drug delivery. PMID- 20352882 TI - Sharp high-aspect-ratio AFM tips fabricated by a combination of deep reactive ion etching and focused ion beam techniques. AB - The shape and dimensions of an atomic force microscope tip are crucial factors to obtain high resolution images at the nanoscale. When measuring samples with narrow trenches, inclined sidewalls near 90 degrees or nanoscaled structures, standard silicon atomic force microscopy (AFM) tips do not provide satisfactory results. We have combined deep reactive ion etching (DRIE) and focused ion beam (FIB) lithography techniques in order to produce probes with sharp rocket-shaped silicon AFM tips for high resolution imaging. The cantilevers were shaped and the bulk micromachining was performed using the same DRIE equipment. To improve the tip aspect ratio we used FIB nanolithography technique. The tips were tested on narrow silicon trenches and over biological samples showing a better resolution when compared with standard AFM tips, which enables nanocharacterization and nanometrology of high-aspect-ratio structures and nanoscaled biological elements to be completed, and provides an alternative to commercial high aspect ratio AFM tips. PMID- 20352883 TI - Growth and cathodoluminescence of Eu doped ZnO nanoneedles and branched nanoneedle structures. AB - Rare-earth (RE) ions are widely investigated luminescent centers because their intraionic-4f transitions generate narrow and intense emission lines. In this work Eu doped ZnO nanoneedles have been grown, by a thermal evaporation deposition method, and structural and luminescence characterization has been carried out. Mixtures of ZnO and Eu2O3 or of ZnS and Eu2O3 powders were used as precursors. Annealing of the compacted powder mixtures leads to the growth of nanoneedles and nanoneedle networks, as well as rods. EDS and CL measurements enable to detect the incorporation of Eu in these structures. The choice of precursor, ZnO-Eu2O3 or ZnS-Eu2O3 influences the morphology as well as the luminescence properties of the obtained nanostructures. In particular, while in the samples obtained from ZnO, the defect green luminescence band is practically absent, the band is present in the ZnO nanoneedles obtained from ZnS. Besides the broad deep level band, a series of well-separated narrow-peaks characteristic of the intrinsic red luminescence of Eu+3 ions are observed in all cases, whose relative intensities vary from one set of samples to the other. The results suggest that the Eu3+ ions have at least, two possible configurations in the ZnO lattice with different symmetry in the nanoneedles. PMID- 20352884 TI - Patterned carbon nanotubes fabricated by the combination of microcontact printing and diblock copolymer micelles. AB - A convenient approach to synthesize patterned carbon nanotubes (CNTs) of three morphologies on printed substrates by combination of microcontact printing (microCP) and a plasma-enhanced chemical vapor deposition (PECVD) process is presented. Micelles of polystyrene-block-poly-(2-vinylpyridine) (PS-b-P2VP) in toluene were used as nanoreactors to fabricate FeCl3 in the core domains, and the complex solution was used as an ink to print films with polydimethylsiloxane (PDMS) stamps, different morphologies (porous, dots and stripes patterns) of the FeCl3-loaded micellar films were left onto silicon substrates after printed. After removing the polymer by thermal decomposition, the left iron oxide cluster arrays on the substrate were used as catalysts for the growth of CNTs by the process of PECVD, where the CNTs uniformly distributed on the substrates according to the morphologies of patterned catalysts arrays. PMID- 20352885 TI - The immunotherapeutic effect of Fe3O4 nanoparticles as adjuvants on mice H22 live cancer. AB - The aim of this paper is to prepare Fe3O4 nanoparticles and study its immunotherapeutic effect as adjuvants on mice H22 live cancer. The Fe3O4 nanoparticles were prepared by chemical coprecipitation route. Transmission electron microscopy (TEM), X-ray diffraction (XRD), Energy Dispersive Analysis (EDS) were used to characterize Fe3O4 nanoparticles. The Fe3O4 nanoparticles were compared with the common alum adjuvants for its ability to induce immunity to inhibit tumor growth rate by prophylactic and therapeutic studies. Results indicated that Fe3O4 nanopaticles adsorbed autovaccine took great advantages over the common alum adjuvants after subcutaneous injection, raised the mass inhibitory rate of tumor, boosted the activity of cytotoxicity and enhanced the level of IFN-gamma cytokine. Thus, we concluded that Fe3O4 nanoparticles as adjuvants had great potential for enhancing anti-tumor immune response. PMID- 20352886 TI - Preparation of photocontrollable, nontoxicity complex of phenylazophenylalanine modified CdS quantum dots with cyclodextrin. AB - A novel complex of beta-cyclodextrin with phenylazophenylalanine (PAP)-conjugated CdS quantum dot (Fazo-CdS QD) was fabricated for a photocontrollable toxicity study of CdS. Photocontrolling release of Fazo-CdS QDs from the complex was confirmed under UV irradiation by the steady state photoluminescence (PL) spectroscopy. The cytotoxicity of the surface modified CdS QDs was evaluated in vivo. The results suggest that the Fazo-CdS QDs conjugated with beta-CD could be almost nontoxicity, which may have great potential applications in biological labeling and imaging. PMID- 20352887 TI - Evolution of vibrational modes of SiO2 during the formation of Ge and Si nanocrystals by ion implantation and magnetron sputtering. AB - Structural variations of SiOx matrix have been studied with Fourier Transform Infrared Spectroscopy (FTIR) during the formation of Si and Ge nanocrystal. Two frequently used methods, magnetron sputtering and ion implantation have been employed to form SiOx matrix containing excess Si and Ge. The Si-O-Si stretching mode has been deconvoluted to monitor the evolution of SiOx films during the annealing process. The integrated area and the shift in the SiOx peak positions are found to be well correlated with the change of the film stoichiometry and nanocrystal formation. It is shown that the nonstoichiometric SiOx matrix turns into stoichiometric SiO2 as the excess Si and Ge atoms precipitate to form nanocrystals. This process takes place at much lower temperatures for Ge than Si for both ion implantation and magnetron sputtering. FTIR technique is shown to be useful to study the matrix hosting nanocrystals to monitor nanocrystal formation. PMID- 20352888 TI - Preparation and shape-control of Bi2S3 nanocrystals. AB - Stable Bi2S3 colloidal nanocrystals with sphere or rod shape were synthesized through a "hot injection" method using organic molecules and macromolecules as ligands. The morphology of Bi2S3 nanocrystals is highly dependent on the experimental parameters, including the reaction temperature, reaction time, reactant ratio and ligands. Especially, adjusting the properties of ligands can lead to an obvious shape evolution of Bi2S3 nanocrystals. When polyvinylpyrrolidone is added as ligands before the reaction, a stable nanodot colloid is formed. While using polyvinylpyrrolidone and thioglycolic acid as mixed ligands benefits for the formation of Bi2S3 nanorods. The synthesized Bi2S3 nanorods were used as seeds in the second-step growing process to achieve a stable, shape and size controlled Bi2S3 nanocrystals. The Bi2S3 nanocrystals were characterized by XRD, UV-Vis and TEM. PMID- 20352890 TI - Synthesis of conducting polyaniline nanofibers from single and binary dopant agents. AB - Conducting polyaniline nanofibers (nf-PANI) were successfully synthesized by simple polymerization of aniline in presence of single and binary dopant agents. Strong hydrochloride acid (HCl), two weak organic acids (poly acrylic acid, PAA, 2-acrylamido-2-methyl-1-propanesulfonic acid, AMPSA) and one anionic surfactant (sodium dodecyl sulfate, SDS) were used to form the binary dopant agents. The binary dopant agent PAA modified the morphology of the single doped PANI, whereas AMPSA and SDS modified the dimensions of the nanofibers: the length size single nanofibers is reduced 1.72 times with binary-doped AMPSA and increased by a factor of 0.7 with SDS. The surface roughness of the films decreases when the dimensions of the nanofibers increase: PANI-SDS film is flatter than PANI-AMPSA film. In general, the conductivity of the single-doped PANI nanofibers (nf-PANI HCl) was improved by one order of magnitude with binary dopant agents (HCI-PAA, HCl-AMPSA, HCl-SDS). The influence of the binary dopant agents in the nf-PANI-HCl properties is analyzed by Transmission Electron Microscope (TEM), Atomic Force Microscopy (AFM), UV-VIS absorption spectra, thermogravimetric analysis (TGA) and Fourier-Transform infrared spectra (FT-IR). PMID- 20352889 TI - Self-assembly of SiO2/Gd-DTPA-polyethylenimine nanocomposites as magnetic resonance imaging probes. AB - Controlled self-assembly of organic/inorganic magnetic hybrid materials have important applications in magnetic resonance imaging (MRI). In this study, a widely used polycation polyethylenimine was conjugated with gadopentetic acid (Gd DTPA) as a gadolinium bearing polyelectrolyte (Gd-DTPA-PEI). Next, multilayers of Gd-DTPA-PEI were coated on silica nanoparticles through layer-by-layer (LbL) self assembly with polyanions as monitored by dynamic light scattering, zeta potential, and scanning electron microscopy. The thickness of the multilayer film was estimated from quartz crystal microbalance based on counting frequency change of each adsorbed layer. The magnetic relaxation of SiO2/(Gd-DTPA-PEl/polyanion), core-shell nanocomposite was tested at 1.5 T magnetic field in a clinical MRI scanner, and a 3-fold increase in T1 relaxivity to 15.1 Gd mM(-1)s(-1) was noticed comparing to Gd-DTPA small molecules. Dextran sulfate was coated as the outermost layer on the nanocomposite for better biocompatibility as verified by in vitro cytotoxicity studies. This formulation provides good signal intensity enhancement of mouse liver in vivo with only 1/25 dose of clinical standard at 30 and 60 minutes after intravenous injection. This sensitive imaging probe with unique core-shell structures may find broad applications in cellular and molecular imaging. PMID- 20352891 TI - A new chemical approach to the low-temperature growth of single crystalline trigonal selenium scrolled nanotubes and nanowires. AB - In this paper, we present the formation of high quality trigonal phase selenium (t-Se) scrolled nanotubes and nanowires at 100 degrees C by a simple wet chemical method using of Na2S as new reducing agent and poly(vinylpyrolidone) (PVP) as the stabilizing agent. The Na2S used in this method is not only cheaper and easily available but also easy to handle as compared to many earlier reported inorganic reducing agents e.g., hydrazine hydrate, hydroxyl amine hydrochloride, sodium borohydride, H2O2 etc. The phase purity of the as obtained product is confirmed by X-ray diffraction (XRD), Raman spectroscopy. We have also proposed a possible growth mechanism for the formation of scroll-type nanotubes on the basis of a series of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies of the product obtained at different reaction durations. PMID- 20352892 TI - In vitro study of silica nanoparticle-induced cytotoxicity based on real-time cell electronic sensing system. AB - The biological fate and potential toxicity of nanoparticles have become hot topics since the use of nanoparticles was extended to the biomedical and biotechnological field. In this paper, an in vitro study of silica (SiO2) nanoparticle-induced cytotoxicity was presented mainly by real-time cell electronic sensing (RT-CES) system, which could be used for label-free, dynamic measurement of cell responses to cytotoxicants. The cytotoxicity of both 20-nm silica nanoparticles and microscale SiO2 powder in cultured RAW264.7 cells at dosage levels from 31.25 to 8000 microg/ml was evaluated comparatively. The experimental results showed that the cell index (CI) decrease induced by SiO2 nanoparticles appeared earlier than that by the microscale SiO2 powder at the same dose. The nanoparticles in the dose of 500 micdrog/ml had the toxic effect by the Cell Index Curves of RT-CES, while the microscale SiO2 powders in the same dose did not show obvious effect. The above experimental results were compared with the experiments of a tetrazolium compound-based colorimetric method (MTT assay) and LDH activity in medium. The results showed that the RT-CES assay displayed equal sensitivity and correlation to MTT assay. LDH activity caused by SiO2 nanoparticles at dose of 250 and 500 microg/ml was higher than that by microscale SiO2 particles, which indicated that the exposure to SiO2 nanoparticles could result in a dose-dependent cytotoxicity in cultured RAW264.7 cells due to cell membrane injury. The RT-CES system allows a realtime, continuous monitoring and quantitative recording of the whole assay process and provides a new insight into the cell-toxicant interaction. PMID- 20352893 TI - In vitro phototoxicity of liposomes and nanocapsules containing chloroaluminum phthalocyanine on human melanoma cell line. AB - In this study, the photodynamic action of liposomes (LP) and nanocapsules (NC) containing Chloroaluminum phthalocyanine (CIAIPc), on the human melanoma cell (WM 1552C), was assessed. The light source was setup at 672 nm, which corresponds to the maximum absorption wavelength of the CIAIPc. Both colloidal carriers presented size in nanometric scale as well as negative zeta potential. The cellular damage was light dose dependent ranging from 30% of cell death at 70 mJ x cm-2 to 90% of death at 700 mJ x cm(-2). However, the photocytotoxic effect of LP at 70 mJ x cm(-2) was slightly more efficient to induce cellular death than NC formulation. At 140 mJ x cm(-2), and 700 mJ x cm(-2) both nanocarriers were equally efficient to induce cellular damage. Therefore, in the present work, the maximum phototoxic effect was obtained with 700 mJ x cm(-2) of light dose, in combination with 0.29 microg x mL(-1) of CIAIPc encapsulated into LP and NC. The cells were also positive to annexin V, after the PDT treatment with LP and NC, showing that one of the mechanisms of cellular death involved is apoptosis. In summary, the potential of LP and NC as a drug delivery system, in Photodynamic Therapy (PDT) against melanoma, has been confirmed using a lower concentration of the photosensitizer and lower light doses than that applied in current protocols. This is an innovative proposal to treat melanoma cell lines that until now have not received the benefit of the PDT protocol for treatment. PMID- 20352894 TI - Synthesis and luminescence of hollow spherical Eu3+- or Tb3+ -doped MgAl2O4 phosphors. AB - Eu3+- or Tb3+ -doped MgAl2O4 hollow spheres have been successfully synthesized via facile hydrothermal method by using carbon spheres as template followed by a subsequent heat treatment. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that the hollow microspheres possessed diameters in the range of 1-2.5 microm and shell thickness of 60-80 nm. A possible formation mechanism for hollow spheres was proposed. MgAl2O4:Eu3+ show strong red emission at 619 nm corresponding to the forced electric dipole (5)D0- >(7)F2 transition of Eu3+, and MgAl2O4:Tb3+ exhibit strong green emission at 545 nm corresponding to 5D4-->(7)F5 transition of Tb3+. PMID- 20352895 TI - Development of a nanocomposite system by combining an organic dyad 1-(4-chloro phenyl)-3-(4-methoxy-naphthalen-1-yl)-Propenone with semiconductor TiO2 nanoparticles. AB - Steady state and time resolved spectroscopic measurements on an organic dyad, 1 (4-chlorophenyl)-3-(4-methoxy-naphthalen-1-yl)-propenone, where the donor 1 methoxynaphthalene is connected with the acceptor p-chloroacetophenone by an unsaturated olefinic bond, in presence of TiO2 nanoparticles were made at the ambient temperature. Time resolved fluorescence measurements reveal that the rate parameters associated with charge separation, kCS, within the dyad increases whereas charge recombination rate reduces when the surrounding medium is changed from chloroform to TiO2 nanoparticles. The observed results indicate that the dyad being combined with TiO2 nanoparticles may form organic-inorganic nanocomposite systems useful for developing light energy conversion devices. PMID- 20352896 TI - Sintering photonic beads for multiplex biosensing. AB - Monodispersed silica nanoparticles were assembled into opaline photonic crystal beads and cemented together by sintering in order to enhance the mechanical stability of the beads, which simulates the formation of nature opal. The sintering temperatures and structures of the sintered beads were investigated. The results showed that by sintering treatment at temperatures between 700 degrees C and 1000 degrees C for 2 hours the beads were more reliable for multiplex bioassay applications in mechanical robustness, fluorescent background, sensitivity and encoding ability. It is anticipated that the opal-like beads have wide applications in multiplex protein and nucleic acid analysis. PMID- 20352897 TI - Si-based light-emitting structure synthesized with low-energy ion implantation at a low dosage. AB - In this work, Si-based light-emitting structures were synthesized by Si+ implantation into 30 nm thermally grown SiO2 films with a low dosage (< or =1 x 10(16)/cm2). The emission band of electroluminescence (EL) extends from 300 nm to 700 nm with a peak at around 500 nm. The onset voltage for the EL is around 5 V for the 8 keV implanted sample which is low enough for many device applications. The light emission mechanism is studied in this work. It is believed that the defects in the Si+ implanted SiO2 films are the luminescent centers responsible for the EL. In addition, it is found the light emission intensity can be affected by charge trapping in nc-Si. PMID- 20352898 TI - Charging effect of aluminum nitride thin films containing Al nanocrystals. AB - In this work, the Al-rich AIN thin film is deposited on Si substrate by radio frequency (RF) sputtering to form a metal-insulator-semiconductor (MIS) structure. Al nanocrystals (nc-Al) are formed and embedded in the AIN thin film. Charge trapping/detrapping in the nc-Al leads to a shift in the flat-band voltage (VFB) of the MIS structure. The charge storage ability of the AIN thin films containing Al nanocrystals provides the possibility of memory applications. On the other hand, charge trapping in nc-Al reduces the current conduction because of the breaking of some tunneling paths due to Coulomb blockade effect and the current conduction evolves with a trend towards one-dimensional transport. PMID- 20352899 TI - Effects of intracerebral microinjection of hydroxylated-[60]fullerene on brain monoamine concentrations and locomotor behavior in rats. AB - Fullerenes are condensed ring aromatic compounds with extended pi systems; they have unique cage structures. Current studies suggest that several fullerene derivatives have neuroprotective effects, and it is expected that fullerenes will be useful in drug delivery system and novel medical devices targeting the brain. However, little is known about the effects of fullerenes and its derivative on brain function. We examined the effect of fullerene(OH)24 on the central nervous system in this study. In a V79 colony assay, the IC50 of fullerene(OH)24 was 1.74 microg/ml. In an MTT assay, fullerene(OH)24 reduced proliferation of normal human astrocytes obviously. In an vivo study, 0.25 mg/kg(-1) of fullerene(OH)24 was injected into the lateral ventricle of rat brains. The intracerebral injection of fullerene(OH)24 remarkably decreased body weight and locomotor behavior of rats on day 1, but drastically increased locomotor behavior on day 7. The intracerebral injection of fullerene(OH)24 changed the monoamine concentration greatly on day 1 and slightly on day 30 after the injection. These results suggest that intracerebral injection of fullerene(OH)24 had strong and acute effects on the central nervous system, but that the effects were not permanent. In conclusion, we suggest that fullerene's derivative, fullerene(OH)24 had toxic effects on brain cells and that intracerebral injection of fullerene(OH)24 had acute harmful effects on brain monoamines neurotransmission and locomotor activity. PMID- 20352900 TI - A bioinspired route to various siliceous vesicular structures. AB - Various siliceous nanostructures have been successfully synthesized through the co-organization of organic molecules and inorganic silica source under mild pH conditions (pH approximately 5). A biodegradable block copolymer P123 [EO20PO70EO20, EO is poly (ethylene oxide), PO is poly (propylene oxide)] is employed as a marcomolecular template and Na2SiO39H2O as a silica source. By changing the concentrations of the reactants and/or reaction temperature, siliceous multilamellar vesicles, unilamellar nano-foams and multilamellar vesicles with sponge-like walls have been obtained. Our work provides a convenient and bioinspired route to obtain siliceous nanostructured materials with adjustable and multi-level pore structures as well as rich morphologies, which is important to understand the biomineralization mechanism. Such artificial silica nanoporous materials may find potential applications in catalysis, separations, electronics, and photonics, etc. PMID- 20352901 TI - Drying polymeric drug-loaded nanocapsules: the wet granulation process as a promising approach. AB - The industrial development of polymeric nanoparticle suspensions is still limited due to their low physicochemical stability. In this paper, we evaluated the wet granulation process as an alternative method to dry polymeric nanocapsules using dexamethasone as drug model. Nanocapsule suspensions were used as granulating liquid as well as a drug-loaded-nanocarrier in the wet granulation process. Granules were evaluated regarding their drug content, mean particle size, yield, moisture content, flow properties, stability on storage, recovery studies after water redispersion and morphological characteristics (SEM). Granules containing dexamethasone-loaded polymeric nanocapsules presented good drug content (approximately 94%) and were stable for 6 months at room temperature. Morphological analyses showed nanostructures on their surface and the nanoparticles were recovered after redispersing the granules in water. These results suggest that wet granulation can be an interesting alternative to dry drug-loaded nanocapsule suspensions. PMID- 20352902 TI - Influence of polyethyleneglycol modification on phagocytic uptake of polymeric nanoparticles mediated by immunoglobulin G and complement activation. AB - The purpose of this study is to investigate the influence of polyethyleneglycol (PEG) modification on in vitro phagocytic uptake of polymeric nanoparticles (NPs) mediated by immunoglobulin G (IgG) and complement activation. A series of PEG modified poly (D, L-lactide-co-glycolide) nanoparticles (PEG-PLGA-NPs) were incubated in pure serum protein or whole serum, and their capacity for adsorbing albumin and the serum total proteins was measured by a bicinchoninic acid (BCA) protein assay. The adsorption of serum total IgG and complement activation was investigated by enzyme-linked immunosorbent assay (ELISA). To measure in vitro uptake, various fluorescently labeled (Nile red) PEG-PLGA-NPs were opsonized by different pre-treated sera and subsequently incubated with phagocytes. The uptake of NPs by macrophages was then measured by fluorescence spectrometry. Longer chain length and appropriate content PEG reduced the adsorption of serum proteins and complement activation by NPs via both the classical and the alternative pathways. The phagocytosis of PEG-PLGA-NPs by murine peritoneal macrophages (MPMs) involved both serum-independent and serum-dependent phagocytosis. PEG modification was shown only to reduce serum-dependent phagocytosis, mainly by inhibiting IgG adsorption and complement activation on NP surfaces, and the effect of complement activation was greater than that of IgG. The results of this study provided new information that may assist in the design of more efficient nano drug carriers for medical applications. PMID- 20352903 TI - Metallic copper nanostructures synthesized by a facile hydrothermal method. AB - A facile hydrothermal route has been developed for the synthesis of nearly spherical copper nanoparticles, copper nanocubes and ribbon-like network nanostructures. The as-prepared copper nanostructures were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and UV-vis spectrum analysis. These copper products were fabricated in the presence of surfactant sodium dodecyl benzenesulfonate (SDBS) acting not only as stabilizer but also as size and shape controller via hydrothermal reduction process. HRTEM revealed that the surface of the copper nanostructures was packed with a thin layer of impurities such as oxide combined surfactant or amorphous surfactant. The influence of surfactant concentration and temperature on the resultant copper nanostructures was investigated in details. UV-vis spectra indicated that strong red shift existed for the copper ribbon-like network nanostructures due to the novel morphology as well as the presence of impurities on the surface. PMID- 20352904 TI - Fabrication of nanochannels by anisotropic wet etching on silicon-on-insulator wafers and their application to DNA stretch. AB - We report a new approach to fabricate nanochannels on silicon-on-insulator (SOI) wafers using conventional micromachining techniques. Proper selection of the size of the photomask-window and the thickness of the top silicon layer is necessary to obtain nano-sized regions. Silicon anisotropic wet etching followed by an additional reactive-ion-etching (RIE) process and a second silicon wet etching step resulted in long channels (1 cm) of about 200 nm width and 100 nm depth. Finally, we demonstrated the ability of the nanochannels to stretch random coiled DNA by applying YOYO-1 stained lamda-DNA to the nanochannel sealed by PDMS polymer using fluorescence microscopy. This fabrication method provides a basis for simple and cost-effective mass production of nanochannels with controllable dimensions. It is therefore expected that the nanochannels fabricated have great potential for biological applications. PMID- 20352905 TI - Optical absorption spectra in finite double-walled carbon nanotubes. AB - The tight-binding model and the modified gradient approximation are, respectively, used to calculate the electronic states and optical properties of finite double-walled carbon nanotubes (DWCNTs). The optical absorption spectra allow us to decompose the total DWCNT spectral function into the contributions from the inner and outer walls. Intertube interactions can cause drastic changes in the symmetry of the electronic states, the Fermi level, the energy spacing, and the state degeneracy. Such effects are directly reflected in the joint density of states and optical absorption spectra. Thus, the first absorption peaks of the energy degeneracy (nondegeneracy) of two finite single-walled carbon nanotubes would be separated into three or four peaks in the shorter DWCNTs. For finite armchair DWCNTs, the number of the first group peaks decreases as the length increases. These results demonstrate a competition between the tube length, the intertube interactions, and the geometric structures. For finite zigzag DWCNTs however, the number of the first group peaks remains constant as the length increases. This phenomenon can be attributed to the states exclusively localized at the outermost zigzag positions. The energies of the peaks make a red shift as the tube length increases. For sufficiently long DWCNTs absorption peak energies are almost independent of length. PMID- 20352906 TI - [The design and implementation of video processing system for medical electronic endoscopy]. AB - This paper presents a medical electronic endoscopy real-time image acquisition and control system which consists of video codec chip, flash memory and FPGA. The hardware scheme and circuit design of the system is figured out, and the principle of ping-pong operation and the implementation of FPGA program is introduced. Experimental tests show that the designed system performs steadily, is easy to maintain, and reduces the cost greatly. The higher performance price ratio makes it have good application prospect in medical endoscopy. PMID- 20352907 TI - [Development of a portable dynamic state ECG based on DSP]. AB - The Portable dynamic state electrocardiogram collecting system is introduced by using TMS302VC5402, TLC320AD50C, liquid crystal display model, and so on. This dissertation describes the work principle of the system and uses the united algorithm based on wavelet to identify and locate the ECG characteristic waves. This system has as follows of advantages: big memory, low noise,high common mode rejection ratio, the low power consume,the long record time etc. PMID- 20352908 TI - [The setting up of reflectance confocal microscope and its in vivo application in skin tissue imaging]. AB - This article, introduces setting up of reflectance confocal microscope which is divided into four parts: optical system, scanning system, detecting system and software controlling system. This reflectance confocal microscope realizes in vivo epidermis tissue imaging in mouse skin as well as disease diagnosis related cell parameters measurement. PMID- 20352909 TI - [Research on modeling and simulation of the system of position transformation mechanical ventilation]. AB - The principle of Position Transformation Mechanical Ventilation (PTMV) was introduced briefly, and the mechanical structure and the intelligent control algorithm were studied. According to the principle and function requirement of PTMV, the mechanical structure of slip pole driven rocking chair(SPDRC) was proposed, the dynamics model of SPDRC was established, and the auto disturbance rejection controller was designed. The integrated model of control system was structured by using ADAMS and MATLAB, and the model validation and simulation were implemented. The simulation results indicate that the mechanical structure is feasible and the control process of ADRC is precise and steady. PMID- 20352910 TI - [The computerized clinical practical guideline's research and implementation]. AB - OBJECTIVE: To discuss the development module of ontology-based computerized clinical practical guideline, and to supply the technology support for implement of alerm/reminding, data sharing, evidence-based medicine and clinical decision making in the medical information system. METHODS: Analyse the structure and field ontology of the Guideline Interchange Format (GLIF); expand GLIF based on the Guideline of Cerebrovascular Disease Prevention and Treatment in China and Neurology Disease Ontology. RESULTS: A Chinese computerized guideline of intravenous thrombolytic therapy of acute cerebral infarction is constructed, which included metadata of edition description, list of drug data item, explanation of evidence strength, steps of indications decision, contraindication decision and drug selection. CONCLUSION: The computerized clinical practical guideline combined with clinical information system and Electronic Medical Records plays an important role in clinical pathways optimizing and decision making. PMID- 20352911 TI - [Development of a novel liquid injection system]. AB - A liquid jet injector employs compressed gas or spring to produce a high-velocity stream to deliver liquid drug into human body through skin. There are many clinical jet injection products available, none of which is domestic. A new liquid jet injector is designed based on a comprehensive analysis of the current products. The injector consists of an ejector, trigger and a re-positioning mechanism. The jets characteristics of sample injector are tested, and the results show that the maximum exit pressure is above 15 MPa, a threshold value for penetrating into the skin. PMID- 20352912 TI - [The laboratorial study about relation of balance between trestle and cervical spine of cervical type spondylosis patients]. AB - When 85 cervical type spondylosis patients randomly lay on one's back and on one's right side the 8 different tresles and pillows. We survey indexes of the cervical spine anatomy, for example cervical arcs and angles of cervical spine and level line. We appraise relation of balance between different trestle or pillow and cervical spine. liquid needle-free injection, jet power, stagnation pressure PMID- 20352913 TI - [Development of electronic clinical device for concentrated measurement of body temperature]. AB - An kind of device for concentrated measurement of body temperature which takes ATmega16 microcontroller as the core is designed according to the current situation of measuring body temperature in the hospitals of our country. Taking DS18B20 as the transducer, the device uses PTR8000 wireless communication module to realize the communication from multi-point to single-point. Meanwhile photoelectric detection and USB interfaces are added in the design. Clock chip PCF8563, voice chip ISD1820 and LCD screen I JM12864M are used to realize the functions such as timekeeping, playing voice and displaying and so on. PMID- 20352914 TI - [The design of smart data collection system for EHR]. AB - This paper presents the design of smart data collection system to deal with the drawbacks like EHR data second hand input which is time-consuming and EHR's poor usability. The system comprises security certification, information management and data transmission modules. Through WLAN, EHR data can transmit between smart terminals and server. Also it provides a real-time communication platform for both terminal users and medical care personnel. PMID- 20352915 TI - [Review of wireless energy transmission system for total artificial heart]. AB - This paper sums up the fundamental structure of wireless energy transmission system for total artificial heart, and compares the key parameters and performance of some representative systems. After that, it is discussed that the future development trend of wireless energy transmission system for total artificial heart. PMID- 20352916 TI - [Survey of coronary stents development for restenosis prevention]. AB - Coronary stents are playing an effective way of curing cardiovascular diseases while a major drawback of restenosis is in general still present. Restenosis is resulting from neointimal hyperplasia and thrombosis which induced by the vascular lesion, hemodynamic modification and the reduction or oscillation of wall shear stress (WSS). The crucial factors that would determine the restenosis were reviewed in this paper, including the material bio-compatibilities, surface treatments, stent configuration designs and hemodynamics analyses. In particular, the hemodynamics after stents implantation based on in vivo, in vitro or Computational Fluid Dynamics (CFD) methods was discussed. A novel CFD and experimental approach of dynamics in the stent-vascular coupling system was proposed. PMID- 20352917 TI - [The proposed principles by GHTF of the classification and assessment for in vitro diagnostic (IVD) medical devices]. AB - The IVD (In Vitro Diagnostic)Medical Devices are various and develop rapidly. This paper introduces briefly the principles of classification and conformity assessment for IVD medical that proposed by GHTF (Global Harmonization Task Force). PMID- 20352918 TI - [The study of efficiency and cost of research oriented CT system in Shanghai zone]. AB - The paper is about the study on efficiency and operation cost of 11 research oriented CT systems in Shanghai zone. The study result include the average volume, annual operation cost, cost per scan and break-even-point. It reveals that the research oriented CT system purchase price and operation cost is high. The suggestion is that the hospital should be cautious to select the research oriented CT system with consideration of clinical research demand to avoid unsuitable investment. PMID- 20352919 TI - [Practice and discussion on classified coding management of medical disposable materials]. AB - This paper describes the heart of class supplies involved in bidding and purchasing code library classification principles and, in the hope of medical supplies through the establishment of bidding and purchasing code library to assist the health authorities and medical institutions for effective quality control. Clinical research oriented, CT, volume, operation cost, cost per capita, BEP. PMID- 20352920 TI - [Clinical medicinal engineering support in disaster relief medicine]. AB - Disaster Relief Medicine (DRM), a newly developed science, not only crosses Emergency Service and Critical Health Care, but also relates to other various fields such as Nursing, Clinical examination and Clinical Medicinal Engineering etc, all of which require competent Clinical Medicinal Engineers. Thus, a key subject of Clinical Engineering is to provide quality support to medical equipments, and to offer engineers educational training on this diverse science, in order to improve their professional and managerial skills. Based on DRM characteristics, specifically, based on our first hand experience during disaster relief effort in Wen-Chuan Earthquake, we documents our thoughts and discussion over the issues we found in above areas as listed in the article below. PMID- 20352921 TI - [Practical experience about the compatibility of PDF converter in ECG information system]. AB - OBJECTIVE: To find a way to view ECG from different manufacturers in electrocardiogram information system. METHODS: Different format ECG data were transmitted to ECG center by different ways. Corresponding analysis software was used to make the diagnosis reports in the center. Then we use PDF convert to change all ECG reports into PDF format. The electrocardiogram information system manage these PDF format ECG data for clinic user. RESULTS: The ECG reports form several major ECG manufacturers were transformed to PDF format successfully. In the electrocardiogram information system it is freely to view the ECG figure. CONCLUSIONS: PDF format ECG report is a practicable way to solve the compatibility problem in electrocardiogram information system. PMID- 20352922 TI - [Simplified identification and filter device of carbon dioxide]. AB - This paper presents the design and implementation ways of a simplified device to identify and filter carbon dioxide. The gas went through the test interface which had wet litmus paper before entering the abdominal cavity. Carbon dioxide dissolving in water turned acidic, making litmus paper change color to identify carbon dioxide, in order to avoid malpractice by connecting the wrong gas when making Endoscopic surgery. PMID- 20352923 TI - [Research progress in supramolecular compounds-based stationary phases for capillary electrochromatography]. AB - Supramolecular chemistry is a new branch of sciences, which deals with the specific recognitions between molecules. The host-guest interactions, which exert by supramolecular compounds, can provide a promising prospect for chromatographic separations with high selectivities. Capillary electrochromatography (CEC) is defined as a very promising micro-separation technique with high efficiency and high selectivity in recent years. As the key component of CEC, the stationary phases have been the research focus of CEC development. This paper reviews the recent progress in supramolecular compounds-based stationary phases (cyclodextrin, calixarene, crown ether and macrocyclic polyamine) for CEC since 1998. PMID- 20352924 TI - Quantitative determination of steroids in the fruiting bodies and submerged cultured mycelia of Inonotus obliquus. AB - This study describes the method of quantitative determination of betulin, ergosterol, cholesterol, lanosterol, stigmasterol and sitosterol in the fruiting bodies and submerged-cultured mycelia of Inonotus obliquus. A high performance liquid chromatographic (HPLC) method was applied to separate these steroids. The procedure was carried out on a reversed-phase C, column, using a stepwise gradient of water-methanol as mobile phase with the following profile: 0-10 min, 10% water, 90% methanol; 10-40 min, 3% water, 97% methanol. The flow rate was 1.4 mL/min and the detection wavelength was 202 nm. The analysis was completed within 40 min. The results showed that this method has good reproducibility and satisfactory recoveries for the determination of steroids. The relative standard deviations of the peak areas were less than 2.94% (n = 5) for intraday assays. A good linear correlation was obtained in a range of 0.4-4.8 microg. The recoveries of betulin, ergosterol, cholesterol, lanosterol, stigmasterol, and sitosterol were 100.05%-100.72%, 99.31%-101.04%, 97.52%-101.63%, 96.61%-100.08%, 96.21% 100.76% and 100.04%-100.51%, respectively. This method can be applied to evaluate real samples, and it is rapid, accurate and suitable for the quantitative determination of steroids in the fruiting bodies and submerged-cultured mycelia of Inonotus obliquus. PMID- 20352925 TI - [Evaluation of chromatographic performance of polymerized ionic liquid stationary phase for capillary gas chromatography]. AB - The selectivity and thermal stability of ionic liquids as the stationary phases for capillary gas chromatography (CGC) have attracted much attention of researchers in recent years. In this study, 1-vinyl-3-benzyl imidazolium bis(trifluoromethane-sulphonyl)imidate (VBIm-NTf2) was synthesized and polymerized (PVBIm-NTf2) in a CGC column. In comparison with VBIm-NTf2, PVBIm NTf2 exhibits much better thermal stability and chromatographic selectivity, and achieves satisfactory resolution for Grob test mixture, alcohols mixture, esters mixture and aromatics mixture with narrow and symmetric peak shapes. The satisfactory resolution and selectivity of the polymerized column still remain after conditioned at 250 degrees C for 6 h. Additionally, the Abraham solvation parameters of PVBIm-NTf2 were determined and the interactions between the stationary phase and solutes were elucidated. The present work demonstrates that the polymerization is an effective way to improve the selectivity and thermal stability of common ionic liquids as CGC stationary phases. PMID- 20352926 TI - [Analysis of solvent residues in raw material drug of glimepiride by head-space sampling-capillary gas chromatography]. AB - An analytical method for the solvent residues in the raw material drug of glimepiride has been established by head-space sampling capillary gas chromatography. General evaluation was made for the distribution of organic residual solvents in glimepiride samples from 8 different domestic manufacturers. Based on the evaluation-test results and the information provided by manufacturers, 14 target solvents were ascertained including acetone, ethyl acetate, methanol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine, chlorobenzene, ether, dichloromethane, n-hexane and benzene. The target solvents were divided into two groups for baseline separation according to their column-retention specificity. Acetone, ethyl acetate, methanol, isopropanol, ethanol, chloroform, toluene, 1,4-dioxane, pyridine and chlorobenzene were separated on a Supelco-Wax capillary column with acetonitrile as internal standard, while ether, dichloromethane, n-hexane and benzene were determined on a Supelco OVI-G43 capillary column with butanone as internal standard. Linear responses were obtained for the 14 residual solvents in their respective concentration ranges (r = 0.99167-0.99997, n = 8), and the limits of detection were 0.2-13.5 microg/g. The inter-day reproducibilities, measured as relative standard deviations (RSDs), were 0.6%-9.2% (n = 3). The average recoveries of three concentration levels were 86.3%-104.1% with the RSD of 0.2%-5.3% (n = 16). The developed method is simple, sensitive, and accurate for the residual solvent analysis in glimepiride samples. PMID- 20352927 TI - [Determination of fenbutatin oxide residue in orange products by gas chromatography]. AB - An analytical method for the determination of fenbutatin oxide (FBT) residue in oranges by capillary gas chromatography-flame photometric detection (GC-FPD) was developed. The FBT was extracted with acetone-acetic acid (99:1, v/v) and hexane, filtered and evaporated by nitrogen evaporator in a water bath at 35 degrees C. The residue was dissolved in hexane. The FBT in the solvent was derivatized with ethyl magnesium bromide for 15 min, 1 mol/L hydrochloride was added, the supernatant was collected and the solvent was evaporated to get dry supernatants, then the supernatant was dissolved in hexane and cleaned up with a silica solid phase extraction column, eluted with 5 mL hexane-dichloromethane (4:1, v/v), determined by GC. The standard curve was linear in the range of 0.2-2.0 mg/L. The correlation coefficients (r) were more than 0. 999 5, the average recoveries were 79.6%-109.6% with the relative standard deviations (RSDs) of 3.60%-9.04% at the spiked levels of 0.1-0.4 mg/kg, and the detection limit of fenbutatin oxide was 0.1 mg/kg. This method is suitable for the analysis of fenbutatin oxide residue in orange products. PMID- 20352928 TI - [Preparation and evaluation of Sudan Red I molecularly imprinted polymer]. AB - The molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using Sudan Red I as the template. To investigate the influence of porogenic solvent and the amount of template on recognition property, selective chromatographic evaluation and frontal chromatography were performed. The results indicated that the obtained MIP had the best affinity and selectivity to the template when the molar ratio of template to functional monomer was 1:8 and a mixture of 30 mL methanol and 10 mL acetonitrile was used as the porogenic solvent. The imprinted factor of optimal MIP for Sudan Red I was 2.32, and the total amount of the immobilized ligand was 0.50 micromol/g. This MIP displayed good specific recognition property for Sudan Red I and was used as the sorbent of solid phase extraction (SPE) to determine trace Sudan Red I in chili powders. The linear range was from 10 to 500 micromol/L with a correlation coefficient of 0.999. The detection limit was 3.3 micromol/L, the spiked recovery was between 95.87% and 98.41%, and the relative standard deviation (RSD) was lower than 3.1%. The developed method can be used for the routine detection of Sudan Red I in chili powders. PMID- 20352929 TI - [Application of three-phase hollow fiber liquid-phase microextraction for analysis of hydroxybenzoic acids]. AB - Under the optimal experimental conditions of three-phase hollow fiber liquid phase microextraction (3p-HFLPME), the behaviors of hydroxybenzoic acids (HBAs) were investigated. The correlation between the enrichment factor (EF) of HBAs and their n-heptanol/water conditional distribution coefficients (log P(n-heptanol/5 mmol/L) HCl), pK(a) mmol/L HCI ), and the number of -OH (N); the extraction mechanism that polyvinylidene difluoride hollow fiber contributed to promote the extraction efficiency by forming charge transfer compound with HBAs and the organic solvents showed notable selectivity for HBAs were elucidated. The optimal 3p-HFLPME conditions were: MOF 503 polyvinylidene difluoride hollow fiber as organic solvent supporter, n-heptanol as organic phase, 5 mmol/L HCl in the donor phase and 80 mmol/L NH3 x H2O as the acceptor phase, the HBAs were extracted for 35 min under an agitation of 1 200 r/min. It was found that the relative standard deviations were lower than 3%, the detection limits were 0.09-30.00 microg/L, the average recoveries of HBAs in Calyx Kaki were 93.3%-107.1% and the EF of HBAs at 5 mg/L was up to 107.6 fold. PMID- 20352930 TI - [Discrimination of Ganoderma based on high performance liquid chromatographic fingerprints combined with chemometrics methods]. AB - High performance liquid chromatography (HPLC)-based system was utilized for generating chemical fingerprints of 11 Ganoderma strains. The data were statistically evaluated by using chemometric methods in order to classify the samples. The similarities of all the 11 samples and the relative peak areas of 13 common peaks were newly calculated separately. Then different chemometrics methods including hierarchical cluster analysis (HCA), principal component analysis (PCA) and discriminate analysis (DA) were applied to classify the G. lucidum samples. Consistent results show that the application of HPLC fingerprint coupled with powerful chemometrics analysis in the discrimination and classification of Ganoderma is a reliable and scientific approach. PMID- 20352931 TI - [High performance liquid chromatographic fingerprints of Baihe Zhimu Tang and its correlation to single herb]. AB - The high performance liquid chromatographic (HPLC) fingerprints of Baihe Zhimu Tang were established for evaluating the effective substance basis and compatibility regulation of Baihe Zhimu Tang. An Agela Venusil XBP-C18 column (250 mm x 4.6 mm, 5 microm) was employed, and the gradient elution of acetonitrile and 0. 1% formic acid was used as mobile phase with a flow rate of 1 mL/min, the detection wavelength was set at 315 nm, and the column temperature was set at 25 degrees C. By taking mangiferin as the reference substance, the fingerprints of 10 batches of Baihe Zhimu Tang prepared by Bulbus Lilii and Rhizoma Anemarrhenae from different producing areas were analyzed under the same chromatographic conditions. The results showed that there were 16 common peaks contained in the tested samples. Five constituents were identified as 5 hydroxymethyl-2-furaldehyde (5-HMF), neomangiferin, mangiferin, isomangiferin and regaloside B by comparing the retention times and ultraviolet spectra of the peaks with those of the reference substances. The HPLC fingerprints of Baihe Zhimu Tang established with the above method show good characteristic and repeatability, and the method is stable and reliable, it can be used for the quality control of Baihe Zhimu Tang. The main chromatographic peaks of the HPLC fingerprints of Baihe Zhimu Tang were identified in the experiment and also 5-HMF was identified as the main constituent which changed significantly in decocting process. PMID- 20352932 TI - [Determination of 61 central nervous system drugs in plasma by protein precipitation-high performance liquid chromatography]. AB - A method was established for the determination of 61 central nervous system drugs in plasma by using protein precipitation combined with high performance liquid chromatography-diode array detection (HPLC-DAD). A volume of 1.5 mL acetonitrile was added into 1 mL plasma, after vortex, centrifugation and filtration, the supernatant was directly injected into HPLC. The separation was performed on an Agilent TC-C18 column (250 mm x 4.6 mm, 5 microm) with acetonitrile and phosphate buffer solution as mobile phase by gradient elution at a flow rate of 1.5 mL/min. The detection wavelength was 210 nm; full spectra were recorded from 200-364 nm. The recoveries of 61 drugs were larger than 80% with the relative standard deviations (RSDs) ranged from 0.94% to 11.23%. The protein precipitation method is simple, rapid, low-cost with good recoveries, reproducibility and suitable for the general pretreatment of the systematic toxicological analysis (STA) of the 61 drugs. PMID- 20352933 TI - [Determination of netilmicin in rat plasma by reversed-phase high performance liquid chromatography with fluorescence detection and pre-column derivatization]. AB - A new, simple and sensitive method based on pre-column derivatization by reversed phase high performance liquid chromatography (HPLC) is described for the separation and quantification of netilmicin in plasma, using 9-fluorenylmethyl chloroformate (FMOC-Cl) as the derivatization reagent. Its pharmacokinetics is also presented. The derivatization modes and chromatographic conditions were optimized. The separation was performed on an Agilent ZORBAX Eclipse XDB-C8 column (150 mm x 4.6 mm, 5 microm) with a mixture of water-acetonitrile (15:85, v/v) as mobile phase and the flow rate was 1.0 mL/min. The excitation wavelength was 265 nm and the emission wavelength was 315 nm. The linear range was 0.045 8.88 mg/L and the correlation coefficient (r) was 0.9993. The limit of detection (LOD) (S/N = 3) was about 0.01 mg/L, and the limit of quantification was 0.03 mg/L (3LOD) for netilmicin. The relative standard deviation was less than 3% for intra-day assay (n = 5) and 3.5% for inter-day assay (n = 5) and the relative recovery was in the range of 96.62%-100.84% (n = 3). The plasma volume of 30 microL was sufficient for the determination of netilmicin. The method provides a reliable bioanalytical methodology to carry out netilmicin pharmacokinetics in rat plasma. PMID- 20352934 TI - [Dispersive liquid-liquid microextraction coupled with high performance liquid chromatography for the determination of polynuclear aromatic hydrocarbons in environmental water samples]. AB - A simple, rapid and effective method, the dispersive liquid-liquid microextraction coupled with high performance liquid chromatography-fluorescence detection (DLLME-HPLCFLD), has been developed for the extraction and determination of polynuclear aromatic hydrocarbons (PAHs) in environmental water samples. The factors relevant to the microextraction efficiency, such as type and volume of dispersion agent and extraction solvents and the extraction time were investigated and optimized. Under the optimized extraction conditions, the reliability of the proposed method was evaluated. The linear response of this method was in the range of 0.01-10 microg/L (r > or = 0.9913), the relative standard deviations (RSDs) of peak area for 0.05 microg/L PAHs were in the range of 2.3%-4.7% (n = 6). At room temperature, the method exhibited excellent enrichment factors and good recoveries, 674-1032 and 67.4%-103.2% respectively. The detection limits (S/N = 3) were in the range of 0. 000 3 - 0. 002 pg/L. The developed method was applied to the determination of 15 PAHs in the water from Aojiang river, the average recoveries were 79.5% -92.3% with RSD of 4.3%-6.7% (n = 5). The developed method is suitable for the analysis of trace PAHs in environmental water samples. PMID- 20352935 TI - [Determination of six p-hydroxybenzoates in fruits and jams using solid-phase extraction-high performance liquid chromatography]. AB - A method was developed for the determination of 6 p-hydroxybenzoates (methyl p hydroxybenzoate (MHB), ethyl p-hydroxybenzoate (EHB), isopropyl p-hydroxybenzoate (IPHB), propyl p-hydroxybenzoate (PHB), isobutyl p-hydroxybenzoate (IBHB) and butyl p-hydroxybenzoate (BHB)) in fruits and jams using the combination of solid phase extraction and high performance liquid chromatography (SPE-HPLC). Two different extraction solutions and three different mobile phases were tested for p-hydroxybenzoates analysis, and finally ethanol was used as the extraction solvent and methanol-citric acid buffer was selected as the mobile phase. The sample was extracted, and purified by an Oasis HLB solid-phase extraction cartridge, then separated on a Symmetry-C18 column and detected at the wave length of 258 nm. The results showed that all the calibration graphs were linear in the concentration range of 0.1 -20.0 mg/L (r = 0.9999). The detection limits and quantification limits were 0.1 mg/kg (S/N = 3) and 0.3 mg/kg (S/N = 10) respectively for MHB, EHB, IPHB and PHB, 0.2 mg/kg (S/N = 3) and 0.6 mg/kg (S/N = 10) respectively for IBHB and BHB. The average recoveries were between 82.8% and 115.5% with the relative standard deviations (RSDs) of 0.2%-6.8% (n = 6). The method is simple, rapid, sensitive and reproducible, and can be used for the routine analysis of the p-hydroxybenzoates in fruits and jams. PMID- 20352936 TI - Extraction chromatographic separation of platinum (IV) from real samples and associated elements. AB - The extraction behavior of platinum (IV) was studied with N-n-octylaniline as a function of different parameters, such as pH, concentrations of weak acids, mineral acids, reagents and elution time. A selective method was developed for the extraction chromatographic studies of platinum (IV) and its separation from several metal ions with N-n-octylaniline (liquid anion exchanger) as a stationary phase on silica gel. The quantitative extraction of platinum (IV) was observed with 0.067 mol/L N-n-octylaniline and 0.015 mol/L ascorbic acid at pH 1.0. Metal ion was stripped from the column with water and determined spectrophotometrically with stannous chloride method. The proposed method is free from the interference of a large number of cations and anions. Platinum (IV) was separated from pharmaceutical preparations, alloys and synthetic mixtures. Mutual separation scheme was developed for platinum (IV), palladium (II) and gold (III). The log log plot of N-n-octylaniline concentration versus the distribution ratio indicates that the probable extracted species is [RR'NH2+] x Pt (C6H7O6)3-. PMID- 20352937 TI - [Determination of 5 polyether antibiotics in chicken tissues by liquid chromatography-electrospray ionization tandem mass spectrometry]. AB - A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) method for the determination of 5 polyether antibiotics (lasalocid, salinomycin, monensin, narasin and maduramicin) in chicken tissues was developed. The polyether antibiotics were extracted from chicken tissues with methanol. The extract was evaporated to dry, and redissolved in hexane, then cleaned up on a Sep-Pak Silica solid-phase extraction cartridge. The target drugs were eluted with 6 mL methylene chloride-methanol (90:10, v/v), and the eluate was collected and dried under a gentle stream of nitrogen gas, then the residue was dissolved with 1 mL acetonitrile (containing 0.1% formic acid) and analyzed by LC-MS/MS. The LC separation was performed on a Symmetry Shield reversed phase C18 bonded silica column with acetonitrile (containing 0.1% formic acid)-0.1% formic acid (97:3, v/v) as mobile phase. The quantification was carried out by positive electrospray ionization and multiple reaction monitoring (MRM) mode. The validation was carried out on spiked chicken muscle (spiked at 0.1 -1500 microg/kg) and chicken liver (spiked at 0.2-4500 microg/kg), the average recoveries of target drugs ranged from 71.6%-99.1% with intra-day relative standard deviations (RSDs) of 3.2%-10.7% and inter-day RSDs of 4.6%-14.7%. The limits of quantification (LOQs) in chicken muscle and liver were 0.1-1.0 kg/kg. The results demonstrated that the sensitivity, accuracy and precision of this method meet the requirements of veterinary drug residue analysis. The method is applicable to detect 5 polyether antibiotics in chicken muscle and liver. PMID- 20352938 TI - [Separation and identification of 5 glycosidic flavor precursors in tobacco by ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry]. AB - A qualitative method for the identification of 5 main glycosidic flavor precursors in tobacco was developed by using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS) and gas chromatography-mass spectrometry (GC-MS). The glycosidic flavor precursors in tobacco were extracted with methanol, cleaned up with an XAD-2 column. The aglycones were later released by enzyme-mediated hydrolysis under the condition of pH 5. The 5 volatile aglycone moieties were identified by GC-MS standard spectra library. The precursor ions of glycosides were determined by using electrospray ionization mass spectrometry in negative ion mode, then the 5 glycosidic flavor precursors were identified by using product ion scan (MS2) finally, using UPLC-ESI MS/MS, separation and identification of 5 glycosidic flavor precursors were accomplished on an RP-C,8 column in the multiple reaction monitoring (MRM) mode by using methanol and acetic acid-ammonium acetate aqueous solution as eluent. This work lays a foundation for the analysis of glycosidic flavor precursors without the standards by using liquid chromatography-mass spectrometry. PMID- 20352939 TI - [Determination of sulfite in flue gas desulfurization with seawater by ion chromatography]. AB - The technology for flue gas desulfurization (FGD) with seawater is widely adopted by coal-fired power plants in coastal areas. SO2 in the flue gas is absorbed by alkaline seawater and transfered in aqueous phase as sulfite (SO3(2-)), and most SO3(2-) is transformed to sulfate (SO4(2-)) after an aeration process. The remaining SO3(2-) in the seawater discharged to sea area may be harmful to marine organism because of its biological toxicity, thus it is necessary to determine the concentration of SO3(2-) in the seawater for desulfurization. In this study, the method of determination of SO3(2-) in the seawater by ion chromatography was investigated. The separation was achieved on an IonPac AS14A column with 14 mmol/L NaOH-12 mmol/L Na2 CO3 solution as the mobile phase at a flow rate of 1.2 mL/min, and the detection was performed by a pulsed amperometric detector. Formaldehyde was added as a protective agent when sampling because the SO3(2-) is easy to be oxidized. To avoid the formation of Mg (OH)2 in the mobile phase with high pH value which might block the column, the Mg(2+) in seawater was precipitated by NaOH solution (pH 12.0) before sample determination. The method showed good linearity within the range of 0-100 mg/L with an average recovery of 116.8%. The method detection limit (MDL) reached as low as 0.05 mg/L. The relative standard deviations (RSD) for seawater matrix samples spiked at levels of 7.5, 25.0 and 75.0 mg/L were 2.1% 3.1% and 4.0% (n = 9) , respectively. The method has been applied for the determination of SO3(2-) in flue gas desulfurization seawater with the advantages of being fast, sensitive and selective. PMID- 20352940 TI - [Ion chromatographic analysis and mass spectrometric identification of complexes of metal and ethylenediamine disuccinic acid in plants and soils]. AB - The complexes of metal (Fe (III), Cu, Pb, Zn and Mn) and [S,S'] ethylenediaminedisuccinic acid (EDDS)in plants and soils were determined by using ion chromatography and electrospray ionization mass spectrometry. The separation of metal-EDDS complexes was carried out using the Dionex IonPac AS11-HC column (250 mm x 4.2 mm, 5 microm) with guard column. The mobile phase was 60 mmol/L ammonium nitrate solution at pH 6.5, the flow rate was 1.0 mL/min, and the detection wavelength was 260 nm. The mass spectrometry identification of metal EDDS complexes was performed by using selected ion monitoring (SIM) mode. The results showed that method can be used for Fe(III)-, Pb-, Cu-EDDS complex determination and the detection limits of Fe(III)-, Pb- and Cu-EDDS complexes were 0.38, 0.54 and 0.18 micromol/L. and the recoveries were 99.6%, 100.6% and 97.5%, respectively. The method is simple, sensitive and suitable for either single or simultaneous analysis of Fe (III)-, Cu- and Pb-EDDS complexes in plants and soils. PMID- 20352941 TI - [Fast separation and analysis of water-soluble vitamins in spinach by capillary electrophoresis with high voltage]. AB - In capillary electrophoresis, 0-40 kV (even higher) voltage can be reached by a connecting double-model high voltage power supply. In the article, water-soluble vitamins, VB1, VB2, VB6, VC, calcium D-pantothenate, D-biotin, nicotinic acid and folic acid in vegetable, were separated by using the high voltage power supply under the condition of electrolyte water solution as running buffer. The separation conditions, such as voltage, the concentration of buffer and pH value etc. , were optimized during the experiments. The results showed that eight water soluble vitamins could be baseline separated in 2.2 min at 40 kV applied voltage, 25 mmol/L sodium tetraborate buffer solution (pH 8.8). The water-soluble vitamins in spinach were quantified and the results were satisfied. The linear correlation coefficients of the water-soluble vitamins ranged from 0.9981 to 0.9999. The detection limits ranged from 0.2 to 0.3 mg/L. The average recoveries ranged from 88.0% to 100.6% with the relative standard deviations (RSD) range of 1.15%-4.13% for the spinach samples. PMID- 20352942 TI - [Determination of four amino acids in tea by capillary zone electrophoresis and direct ultraviolet detection without derivatization]. AB - Abstract: Four important amino acids, arginine (Arg), tryptophane (Trp), phenylalanine (Phe) and tyrosine (Tyr) in tea samples with different fermentation processes were simultaneously determined by capillary zone electrophoresis (CZE) using direct ultraviolet detection (UV) at 190 nm. Under the conditions of 20 kV of separation voltage and 25 degrees C of temperature, Arg, Trp, Phe and Tyr were separated successfully within 8 min in 25 mmol/L sodium borate-boric acid (pH 10.0) with the detection limits of 5.0, 1.0, 0.3 and 0.5 mg/L for Arg, Trp, Phe and Tyr, respectively. The relative standard deviations (RSDs) of migration time (n = 7) were all lower than 2.8% and the RSDs of peak electric current (n = 7) were lower than 4.0%. The method was applied in the determination of Arg, Trp, Phe and Tyr in eleven tea samples. The results were satisfactory. This method can provide beneficial reference to evaluation quality of tea. PMID- 20352943 TI - [Determination of dichloromethane and trichloromethane residues in ranitidine hydrochloride by headspace liquid phase microextraction coupled with gas chromatography]. AB - A method for the determination of residual dichloromethane and trichloromethane in ranitidine hydrochloride by headspace liquid phase microextraction coupled with gas chromatography (GC) was developed. A homemade device was used to protect the organic drop. The effects of the nature of extraction solvent, extraction time, extraction temperature and microdrop volume on the extraction efficiency were investigated separately. The optimal experimental conditions were as follows: 2 microL of n-tridecane as extraction solvent, 30 min of extraction time, 60 degrees C of extraction temperature. The correlation coefficients of linear calibration curve were 0.9733 and 0.9724 within the concentration ranges of dichloromethane (1-10 microg/g) and trichloromethane (1-10 microg/g), respectively. The detection limits of dichlormethane and trichloromethane were 0.0273 microg/g and 0.0410 microg/g, respectively, the relative standard deviations were lower than 4.36% and 5.89%, and the recoveries of the method were 93.6%-102% and 98.1% respectively. The method is simple and reliable. PMID- 20352944 TI - [Determination of fosetyl-aluminium by ion-pair reversed phase-high performance liquid chromatography with evaporative light scattering detection]. AB - Ion-pair reversed phase-high performance liquid chromatography (RP-HPLC) with evaporative light scattering detection (ELSD) has been established for the analysis of fosetyl-aluminium and relevant impurities in technical or formulated substance. The method was achieved on a Symmetry Shield RP18 column by using n butylamine as ion-pairing agent. The mobile phase was methanol-redistilled water containing 0.5% n-butylamine which was adjusted pH 5.0 with acetic acid (8:92, v/v) and the flow rate was set at 0.8 mL/min. The active ingredient fosetyl aluminium was successfully separated from relevant impurities under the conditions. The calibration curve was linear in the range of 100-1200 mg/L. The average recoveries of two fortification levels (100 mg/L and 1000 mg/L) were 100.58% and 99.53%, and the relative standard deviations (RSDs) were 0.62% and 0.49%, respectively. The method is rapid, simple and accurate which provides another new and reliable means for the analysis of fosetyl-aluminium in its technical or formulated substance. PMID- 20352945 TI - [Simultaneous determination of 9 water-soluble colorants in cosmetics by high performance liquid chromatography]. AB - An analytical method based on high performance liquid chromatography with diode array detector (HPLC-DAD) has been established for the simultaneous determination of 9 water-soluble colorants (Solvent Green 7, Food Yellow 3, Food Red 17, Acid Yellow 1, Acid Red 33, Food Red 4, Food Red 1, Orange I, Acid Orange 7) in cosmetics. The different kinds of samples were treated with different preparation methods. The obtained liquid samples were analyzed by HPLC using a Diamonsil C18 column (250 mm x 4.6 mm, 5 microm). Acetonitrile-potassium dihydrogen phosphate (KH2PO4) buffer solution (pH 6) was used as the mobile phase for gradient elution. The 9 water-soluble colorants were well separated within 15 min. The average recoveries (n = 9) were from 85.33% to 100.2% with the relative standard deviations (RSDs) between 3.68% and 8.20%. The limits of detection (LOD) were in the range of 0.01-0.1 mg/L. The method is simple, rapid, accurate and suitable for the determination of 9 water-soluble colorants in cosmetics. PMID- 20352946 TI - [Determination of acrylamide residue in cosmetics by isotope dilution-liquid chromatography-tandem mass spectrometry]. AB - Abstract: A comprehensive analytical method based on isotope dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of acrylamide residue in cosmetics. Water-soluble cosmetic sample was extracted with water, and the extract was centrifuged, then the upper solution was cleaned up by an Oasis HLB solid phase extraction cartridge. Oil soluble cosmetic sample was extracted by liquid-liquid partition with n-hexane and water. The qualitative and quantitative analyses were carried out for the analyte in the multiple reaction monitoring (MRM) mode after the chromatographic separation on a Waters Atlantis T3 column (150 mm x 2.1 mm, 3 microm). The quantification was performed with 13C3-acrylamide as internal standard. The limit of quantification (LOQ) for acrylamide was 0.1 mg/kg. The mean recoveries were 87.7%-95.8% at the spiked levels of 0.1-1.0 mg/kg with the intra-day precision less than 10% and the inter-day precision less than 12%. The method is suitable for the determination of acrylamide in cosmetics. PMID- 20352947 TI - [Determination of polymyxin E1 and polymyxin E2 in polymyxin E sulfate using micellar electrokinetic capillary chromatography]. AB - A method of micellar electrokinetic chromatography capillary (MECC) has been established for separating polymyxins E1 and E2 in polymyxin E sulfate and determining the contents of E1 and E2. Several factors including the running voltage, the type of surfactant, concentrations of Brij-35 (polyoxyethylene glycol dodecyl ether), NaCl solution and acetonitrile, pH of phosphate were investigated. Under the optimum conditions (10 kV running voltage, phosphate buffer solution (0.01 mol/L, pH 4.1) containing 30 mmol/L Brij-35, 5% (v/v) acetonitrile, 0.167 mol/L NaCl), E1 and E2 were separated with the resolution of 1.94. The contents of E1 and E2 in polymyxin E sulfate were 67% and 32%, respectively. As an example, the relative standard deviations of the intra-assay and inter-assay of polymyxin E1 on the plate number and peak area were less than 5%. The method is simple, rapid, accurate, and reproducible. PMID- 20352948 TI - [Preface for special issue on enzyme engineering]. AB - Enzyme engineering is a combined technology of enzymology and engineering, which is becoming one of the major fields of modem biotechnology. In recent years, China has made some advances in enzyme engineering research. To promote enzyme engineering research in China, invited reviews and selected research articles were published in this special issue of "Enzyme Engineering". The reviews and research articles focus on the fields of enzymatic conversion, therapeutic enzymes, enzymes as additives to animal feedstuff, enzymes for degradation of organic pollutes, and enzymes for biofuel and biorefinery. PMID- 20352949 TI - [Recent advances in enzyme assays using fluoremetry]. AB - Enzymes play such a pivotal role in cellular metabolism that enzyme assays are important for bio-engineering, disease diagnoses and drug discovery. Among the reported methods, fluoremetry has attracted more and more attention due to its high sensitivity and possibility of continuous dynamic monitoring. The recent progresses and applications in enzyme assays using fluorescent probes were reviewed. Different methods were classified into direct fluorescence detection and indirect fluorescence detection according to their labeled substrates and detection mechanisms. Our writing purpose is to provide the readers with a flavor of the kinds of tools and strategies available in enzyme assays with fluorescent probes. Also, the research situation and prospects were disucssed PMID- 20352950 TI - [Engineering the enantioselectivity of biocatalysts]. AB - Wild-type biocatalysts usually show high activity and selectivity towards their native substrates. Since non-native substrates are often used in synthetically useful biocatalytic transformations, it is necessary to engineer enzymes for improved activity, stability and selectivity (chemo-, regio- and stereoselectivity). Herein we give an overview of the recent advances in engineering the enantioselectivity of biocatalysts, with an aim to stimulate further development of this important field in China. PMID- 20352951 TI - [Recent trend of nonaqueous enzymology and biocatalysis in nonaqueous media]. AB - With the rapid development of industrial biotechnology, breakthrough in enzymology and biocatalysis has been made in recent years, especially in areas of stability and activity of enzyme in nonaqueous media, screening, construction and modification of solvent-tolerant biocatalysts, as well as the development of green solvent with excellent biological and environmental compatibility. Recent trend and future focus include: in silico virtual screening and construction of solvent-tolerant biocatalysts based on bioinformatic technology, modification and construction of native solvent-tolerant biocatalysts, the development of environmental friendly green solvent such as ionic liquids. PMID- 20352952 TI - [Yeast cell surface display and its application of enzymatic synthesis in non aqueous phase]. AB - Yeast surface display involves that the exogenous protein, which was fused with the yeast outer shell cell wall protein, was genetically anchored on the yeast cell surface. It has been widely used in expression and screening of functional protein. Here, we focused on the construction of lipase-displaying systems and its application in enzymatic biosynthesis, such as fatty acid methyl esters, short-chain flavour esters and sugar esters applications, and so on. PMID- 20352953 TI - [Enzymatic catalysis in non-aqueous solvents]. AB - It is well known that non-aqueous enzymatic catalysis has emerged as an important area of enzyme engineering with the advantages of higher substrate solubility, increased stereoselectivity, modified substrate specificity and suppression of unwanted water-dependent side reactions. As a result, non-aqueous enzymatic catalysis has been applied in the biocatalytic synthesis of important pharmaceuticals and nutriceuticals. With the advancement of non-aqueous enzymatic catalysis in recent years, the efforts have been centered on the discovery and modification of solvent-tolerant biocatalysts for non-aqueous environments. Additionally, with the inevitable trends of green chemistry and sustainable development, green solvents have been utilized for increased number of enzymatic reactions to replace conventional organic solvents. In this review, modification, immobilization and mutagenesis of various enzymes for non-aqueous catalysis are discussed. Recent progress of non-aqueous enzymatic catalysis in solvent-free environments, reverse micelles, supercritical liquid and ionic liquid are also presented. In particular, while direct evolution, high-throughput screening and site-directed mutagenesis are combined as powerful tools for protein engineering, vapor/solid/ice water mixture, sticky solid-state liquid crystal and high density salt suspension are the future directions for solvent engineering in order to broaden the utility and elevate the efficiency of non-aqueous enzymatic catalysis. PMID- 20352954 TI - [Applications of nitrile converting enzymes in the production of fine chemicals]. AB - Nitriles are an important type of synthetic intermediates in the production of fine chemicals because of their easy preparations and versatile transformations. The traditional chemical conversion of nitriles to carboxylic acids and amides is feasible but it requires relatively harsh conditions of heat, acid or alkali. Nitrile converting enzymes (nitrilase, nitrile hydratase and amidase) which are used as biocatalyst for the production of fine chemicals have attracted substantial interest because of their ability to convert readily available nitriles into the corresponding higher value amides or acids under mild conditions with excellent chemo-, regio- and stereo-selectivities. Many nitrile converting enzymes have been explored and widely used for the production of fine chemicals. In this paper, various examples of biocatalytic synthesis of pharmaceuticals and their intermediates, agrochemicals and their intermediates, food and feed additives, and other fine chemicals are presented. In the near future, an increasing number of novel nitrile converting enzymes will be screened and their potential in the production of useful fine chemicals will be further exploited. PMID- 20352955 TI - [Impact of the industrial enzyme progress on the production of chemicals]. AB - Industrial enzymes play dual roles for the production of chemicals and biochemicals, one is to act as direct catalyst for the reaction, the other is to participate in the fermentation process to convert substrates to fermentable sugars or to make it more efficient. The review briefs the applications of industrial enzymes for chemical productions, with emphasis on direct conversion of starch and their roles in bioethanol production process, also analyzes the benefits by using new enzymes and prospects for future development. PMID- 20352956 TI - [Advances in microbial production of alkaline polygalacturonate lyase and its application in clean production of textile industry]. AB - We reviewed the microbial production of alkaline polygalacturonate lyase (PGL) and its application in the clean production of textile industry. Currently PGL is mainly produced by microbial fermentation and Bacillus sp. is an ideal wild strain for PGL production. Microbial PGL production was affected by many factors including the concentration and feeding mode of substrate, cell concentration, agitation speed, aeration rate, pH and temperature. Constructing the recombinant strain provided an effective alternative for PGL production, and the concentration of PGL produced by the recombinant Pichia pastoris reached 1305 U/mL in 10 m3 fermentor. The recombinant Pichia pastoris had the potential to reach the industrial production of PGL. PGL can be applied in bio-scouring process in the pre-treatment of cotton. Compared with the traditional alkaline cooking process, the application of PGL can protect fiber, improve the bio scouring efficiency, decrease energy consumption and alleviate the environmental pollution. The future research focus will be the molecular directed evolution of PGL to make PGL more suitable for the application of PGL in bio-scouring process to realize the clean production of textile industry. PMID- 20352957 TI - [Advances in cutinase research]. AB - Cutinase (EC 3.1.1.74) is a kind of hydrolase capable of catalyzing the cleavage of ester bonds of cutin to release fatty acids. Cutinase displayed hydrolytic activity not only toward cutin but also a variety of soluble synthetic esters, insoluble triglycerides and polyesters. Besides its hydrolytic activity, cutinase also showed synthetic activity and transester activity. Therefore, cutinase was evaluated as a versatile lipolytic enzyme used in food and chemical industry. Recently, it is found that cutinase has potential use in cotton bio-scouring and synthetic fibers modification. Cutinase is the most important enzyme in clean production of textile industry. PMID- 20352958 TI - [Culture-independent digging of cellulases and genes from natural environments]. AB - There is a great diversity for cellulolytic microbes in nature and the strategies they use to digest cellulose. In addition to the cultured cellulolytic microbes, there are still a great number of microbes being not readily culturable in natural environments, which may represent great potential for identifying novel cellulases and their encoding genes. The rise of metagenomics and metaproteomics provides essential technologic tools to dig up these resources and significant progress has been made so far. This review gives an insight into some relative results that have arisen from the meta-genomic or proteomic analysis of definitive uncultured microbe communities. Their potential role in elucidating the process and mechanisms of cellulose degradation in natural environment from the point of "community system microbiology" is also discussed. PMID- 20352959 TI - [Research and development of enzymes used in feed]. AB - Enzymes can degrade the anti-nutrient factors in feedstuff, increase nutrient digestibility, and reduce pollution to environment, and have been widely supplemented in animal feedstuff. However, the use of enzymes is limited because of their undesirable properties, such as thermoliability and susceptibility against protease digestions. And its commercialization is also limited by low production efficiency and high cost. Therefore, the focuses for future enzyme development will be: (1) to obtain novel enzymes with better properties by high throughput screening of enzyme encoding genes, especially those from extreme and special environments; (2) to improve enzyme properties using directed mutagenesis and protein engineering methods; (3) to achieve high-level fermentation of enzymes by heterogonous expression and optimization of codons, vectors and fermentation conditions; (4) to determine the effect of enzymes to animals and utilize enzymes efficiently. PMID- 20352960 TI - [Progress in the research of therapeutic enzyme]. AB - With the development of the research on biotechnology and modern pharmacy, the application of enzyme drugs have grown rapidly and enzyme drugs have become an important branch of biopharmaceutics. In this article, some new varieties of therapeutic enzymes, enzyme targets, mechanisms and new technologies of application in therapeutic enzymes were reviewed, and the direction of development of therapeutic enzymes were discussed. PMID- 20352961 TI - [Microorganisms of special herb-glycosidases and their fermentation, enzyme properties]. AB - Herb-glycosides are main active elements of Zhongcaoyao (Chinese traditional medicines, Chinese medical herbs). However, the herb-glycoside structures are not optimal active structure for the human bodies. After orally taken up, the herb glycosides of Zhongcaoyao could be changed into other more active structures by the digestive system such as enzymes and intestinal microorganisms; then degraded and absorbed in the human body and play the real role of pharmic effect; but only a small amount could be changed and controlled by circadian state of the human body. If this biochange of herb-glycosides to more active structures in vivo was finished in vitro, it is very useful for the development of the Chinese traditional medicines, new plant medicines, health food, and function cosmetics. To biotransformate herb-glycosides to more active structure, this paper introduced the studies of author's team on the new microorganism isolation of the special herb-glycosidases and enzyme fermentation, the special enzyme purification and characterization. PMID- 20352962 TI - [Progress in study on microbial enzymes for the metabolism of environmental refractory organic compounds]. AB - With the rapid development of socialization and industrialization, more and more pollutes were produced and discharged into natural environment. It is harmful to human health and life. These pollutes included refractory degradation organic compounds like PAHs, RDX, HMX, CL-20, PCBs and alkanes and their relative substances. Various compounds exist in nature with long life span. They are the most hazardous than other organics. The impact of pollutes can be treated by microorganisms. Results showed that it is an effective way for bioremediation of these pollutes with microbial metabolism or cometabolism. A few key enzymes, mainly oxidative and reductive enzymes, connected with the first step of initial degradation. Normally, enzymes grouped with other active fraction on the cell membrane are composed of one oxidative and reductive system for substrates oxidation. The metabolic intermediates can be used with TCA by microorganisms. The pathways of metabolism and the key enzymes were summarized. The further research topics should be focused on microorganism screen and its relative enzyme, pathway and mechanism of metabolism or cometabolism for such compounds degradation, and the result was hoped for the environmental protection. PMID- 20352963 TI - [Progress in silicatein from sponges]. AB - Sponges (Porifera) are the oldest living metazoan in the world, among which most of them (Demospongia) can produce silicic skeleton from orthosilicic acid in the seawater under the natural enVironmental conditions. These biosilicic materials exhibit good mechanical and optical properties as well as good biocompatibility. During the biosilicification process of sponges, a protein, named as silicatein, plays an important role and has attracted great attention from biologist, chemists and material scientists. This mini review highlights the discovery of silicateins and its function as both an enzymatic catalyst and an organic template for biosilicification. The studies since 1999 were briefly introduced on the application of silicatein as a biocatalyst and template for synthesis of silica-based and other inorganic materials. It is expected to stimulate the interests in the related researches in China. PMID- 20352964 TI - [H2O2 induces changes in the plasma membrane of Saccharomyces cerevisiae]. AB - This article reviews the recent studies on H2O2 adaptation of Saccharomyces cerevisiae. When the cell exposed in the H2O2 sub-lethal doses, the plasma membrane permeability decreased, meanwhile the plasma membrane fluidity is minished. These changes resulted in a gradient across the plasma membrane, which conferring a higher resistance to oxidative stress. Recent work has also shown that the yeast cells adapted to H2O2 would lead to several changes in the expression of genes coding the key enzymes involved in the biosynthesis of lipid profile and in the organization of lipid microdomains of the plasma membrane, which finally decreased its' permeability and fluidity. The reorganization of the plasma membrane might be the major mechanism of the H2O2 adaptation. Once the yeast cells adapted to the external H2O2, changes in plasma occurred. The H2O2 dependent signaling pathways in the plasma membrane might be activated by high levels of H2O2. But the details of the signaling events should still be further studies. PMID- 20352965 TI - [Increasing activity of Rhizopus chinensis CCTCC M201021 lipase by directed evolution-error prone PCR]. AB - Directed evolution strategy (error-prone PCR) was conducted to improve the activity of lipase from Rhizopus chinensis CCTCC M201021. Through two rounds of ep-PCR and pNPP top agar screening, two optimum mutant strains 1-11 and 2-28 were obtained with 2 and 4 fold of enzyme activity higher than that of parent strain, respectively. DNA sequencing of mutant lipase 2-28 revealed four amino acid substitutions: A129S, K161R, A230T, K322R. According to the simulated protein structure of Rhizopus chinensis lipase, A129S, K161R, A230T were located on the surface of the protein. A230T substitution improved the stability of the alpha helix loop. K322R, near the catalytic center of lipase, located at a loop, formed a salt-bridge with a nearby aspartic acid (negative charged). Electrostatic force pulled the loop to the opposite direction of the substrate channel and made it easier for substrate to enter the lipase catalytic domain. Purified lipase was characterized and the result showed that Km of 2-28 lipase decreased by 10% compared with Km of the parent lipase, and Kcat was 2.75 fold improved than that of the original lipase. PMID- 20352966 TI - [Directed evolution by error-prone PCR of Armillariella tabescens MAN47 beta mannanase gene toward enhanced thermal resistance]. AB - Firstly, We used error-prone PCR to induce mutations on Armillariella tabescens MAN47 beta-mannanase gene, Secondly, we cloned the mutated fragments into secreted expression vector pYCalpha, Then the recombinant plasmids were transformed into Saccharomyces cerevisiae BJ5465 after amplified and extracted in DH5alpha cells. Through three cycles of error-prone PCR we built a mutant database, Then we screened one optimum (named M262) from about 104 mutants. The evoluted MAN47 beta-mannanase displayed both higher thermal stability and activity than wide type. The evoluted enzyme M262 retained high activity after treatment at 80 degrees C for 30 min, whereas, the wild type nearly lost activity under this condition. Meanwhile, the activity of M262 can reach to 25 U/mL, which is 4.3 times as wide type under optimum temperature. In addition, pH stability and pH range of evoluted enzyme M262 were both improved compared with wild-type enzyme. The optimum pH was estimated to be similar to that of wild-type enzyme. The sequence comparison illustrated that there were three nucleotide substitutions (T343A/C827T/T1139C) which carried corresponding amino acid changes (Ser115Thr/Thr276Met/Val380Ala). According to homologous modeling by SWISS-MODEL Repository, three mutated amino acids located at the sixth amino acid of the fourth beta-sheet, the first amino acid of the sixth alpha-helix, the turn between the tenth and eleventh beta-sheet, respectively. PMID- 20352967 TI - [Improved expression and catalytic efficiency of (R)-carbonyl reductase in Escherichia coli by secondary structure optimization of mRNA translation initiation region]. AB - To improve the expression level and catalytic efficiency of (R)-carbonyl reductase from Candida parapsilosis in Escherichia coli, we optimized the mRNA secondary structure of (R)-carbonyl reductase gene in translation initiation region (from +1 to +78), and constructed the corresponding variant. The formation of hairpin structure was significantly reduced and the Gibbs free energy was dramatically decreased from -9.5 kcal/mol to -5.0 kcal/mol after optimization. As a result, the expression level of (R)-carbonyl reductase in the variant was increased by 4-5 times and its specific activity in cell-free extract was enhanced by 61.9% compared to the wild-type strain. When using the whole cells as catalyst and 2-hydroxyacetophenone as substrate with a high concentration of 5.0 g/L, the variant showed excellent performance to give (R)-1-phenyl-1, 2 ethanediol with optical purity of 93.1% enantiomeric excess and a yield of 81.8%, which were increased by 27.5% and 40.5% respectively than those of the wild-type. In conclusion, the optimization of mRNA secondary structure in translation initiation region can overcome the steric hindrance of translation startup, promote translation smoothly to acquire high expression of target protein, and favor protein folding correctly to efficiently improve the enzyme specific activity and biotransformation function. PMID- 20352968 TI - [Cloning and characterization of a beta-glucosidase from marine metagenome]. AB - In the present study, through a functional strategy, a metagenome library of the marine microbes from the surface water of the South China Sea was screened for beta-glucosidase and six positive clones were obtained. One of these clones, pSB47B2, was subcloned and further analysed in sequence. The result showed that there was an open reading frame for a novel beta-glucosidase, which was nominated as bgl1B. Using pET22b(+) as vector and Escherichia coli BL21(DE3) as host, Bgl1B was overexpressed recombinantly with high yield obtained and substantial enzymatic activity detected. The recombinant protein (rBgllB) was purified by Ni NTA affinity chromatography and further biochemically characterized. The results indicated that, with pNPG as substrate, the optimum pH and temperature for the hydrolytic activity of rBgl1B were about 6.5 and 40 degrees C respectively. Under the optimum conditions, rBgl1B hydrolyzed pNPG with an activity up to 39.7 U/mg, Km and Vmax being 0.288 mmol/L and 36.9 micromol/min respectively. In addition, rBgl1B could also hydrolyze cellobiose, with a Km of 0.173 mmol/L and a Vmax of 35 micromol/min. However, we did not detect evident hydrolytic activity of rBgl1B to lactose, maltose, sucrose, and CMC. The enzymatic activity of rBgl1B to pNPG was stimulated to certain degrees by low concentration of Ca2+ or Mn2+, whereas it exhibited significant tolerance against high Na+. Distinguished from most of the beta-glucosidases derived from fungi, which display the highest activities under acidic conditions, rBgl1B exhibited relatively higher activity and stability at pH between 7.0 and 9.0. PMID- 20352969 TI - [Protoplast mutagenesis for improving beta-glucosidase production of Aspergillus niger]. AB - The aims of this research were to isolate a Aspergillus niger strain with higher beta-glucosidase activity. We utilized the beta-glucosidase producing strain Aspergillus niger CGMCC 3.316 as the original strain to first obtain a mutant 3 3M through ultraviolet irradiation. Then we studied the conditions of protoplast release and regeneration for strain 3-3M. We treated the protoplasts of strain 3 3M via ultraviolet irradiation and obtained another isolated mutant 60B-3D. The strain 60B-3D showed much higher beta-glucosidase production than the original strain and 3-3M strain. The beta-glucosidase activity of strain 60B-3D was 23.4 IU/mL, with an improvement of 39% compared with the original strain, and 23% compared with strain 3-3M. We also studied the fermentation process of strain 60B 3D, and compared it with the original strain and strain 3-3M. We found the strain 60B-3D exhibited an improvement in xylanase production. The comparison results also showed that the strain 60B-3D secreted more protein. These results were beneficial for producing beta-glucosidase through this productive mutant. PMID- 20352970 TI - [Synthesis of flavor esters catalyzed by CALB-displaying Pichia pastoris whole cells in non-aqueous phase]. AB - An enzyme-displaying yeast as a whole-cell biocatalyst seemed an alternative to immobilized enzyme, due to its low-cost preparation and simple recycle course. Here, we tried to use a recombinant Pichia pastoris displaying Candida antarctica lipase B (CALB) to catalyze the synthesis of short chain flavor esters in n heptane. We studied some major influential factors of esterification reactions, such as carbon chain length of the substrates, alcohol structure, enzyme concentration, substrates concentration, molar ratio of the substrates. The acid conversions were determined by titration and gas chromatography analysis. About ten kinds of esters were synthesized successfully, and the acid conversions of eight esters reached as high as 90% after reaction for 6 h. The result also indicated that ethanol and hexanoic acid were the most suitable substrates for this whole-cell catalyst. Under the optimal reaction conditions (the amount of lipase 20 g/L (306.0 U/g-dry cell), hexanoic acid concentration 0.8 mol/L, the molar ratio of hexanoic acid to ethanol 1:1.1), hexanoic acid conversion reached 97.3% after reaction for 1.5 h. To our knowledge, the CALB-displaying P. pastoris whole-cell biocatalyst showed good tolerance for high substrates concentration and exhibited high reaction rate on esterification of short chain flavor esters among the present enzyme/cell reported. Thus, CALB-displaying P pastoris whole cell biocatalyst was promising in commercial application for flavor esters synthesis in non-aqueous phase. PMID- 20352971 TI - [Synthesis of glucose laurate monoester catalyzed by Candida antarctica lipase B displaying Pichia pastoris whole-cells]. AB - We developed a new enzymatic-catalyzing producing process of glucose laurate monoester. In the process we used Candida antarctica lipase B-displaying Pichia pastoris whole-cells as biocatalyst, glucose as the acyl acceptor and lauric acid as the acyl donor. The product glucose laurate monoester was purified by silica gel column chromatography and preparative liquid chromatography, and identified by liquid chromatography-mass spectrometry. Then we optimized the process from various aspects, such as solvent composition, ratio of dmethyl sulfoxide to 2 Methyl-2-butanol (V/V), catalyst dosage, substrate concentration, water activity and temperature. The optimal reaction conditions were: glucose 0.5 mmol/L, lauric acid 1.0 mmol/L, ratio of 2-Methyl-2-butanol to Dmethyl sulfoxide is 7:3 in 5 mL volume, temperature 60 degrees C, the best initial water activity of whole-cells biocatalyst is 0.11. The maximum glucose conversion could be 48.7% after 72 h. PMID- 20352972 TI - [Enzymetic synthesis and characterization of a carnosine analogue in non-aqueous solvent]. AB - Carnosine (beta-Ala-L-His) has high antioxidant activity, and it is widely used in biology, chemical engineering, medicine and other fields. Its analogue syntheised in non-aqueous solvent and catalyzed by enzymes is high-effective but low-price, so it has great prospect. Here, we synthesized a carnosine analogue imidazole 4(5)-alanylamide-5(4)-carboxylic acid with imidazole-4,5-dicarboxylic acid and L-Alanine as substrates, alpha-chymotrypsin as catalyst in tetrahydrofuran (THF) solvent. Based on the orthogonal experiments, the optimized synthetic conditions are 4,5-dicarboxylic acid: L-alanine = 1:3 (m/m), alpha chymotrypsin: substrates (4,5-dicarboxyl acid and L-alanine) = 1:200 (m/m), pH 8 phosphate buffer:THF = 1.6:10 (V/V), reaction temperature 35 degrees C, time 1.5 h. We separated the product with silica gel G60 thin-layer chromatography (TLC), and a new spot appeared at Rf (ratio to front) = 0.81; then the new spot was purified and characterized with UV spectra, high performance liquid chromatogram (HPLC) and 13C NMR (13C nuclear magnetic resonance). The UV spectra shows a new absorption peak at 310 nm, and the peak in 253 nm is largely strengthened; HPLC reserve times are all 4.5 min at 253 nm, 310 nm, 330 nm; 13C NMR shows 8 carbons. Combing with the catalytic mechanism of alpha-chymotrypsin, structure of the analogue is confirmed, i.e., imidazole 4(5)-alanylamide-5(4)-carboxylic acid. PMID- 20352973 TI - [Expression of Paenibacillus macerans cyclodextrin glycosyltransferase in Pichia pastoris and Bacillus subtilis]. AB - The cgt gene was isolated from Paenibacillus macerans by PCR amplification and was inserted into vectors of pPIC9K and pMAS. The recombinant vectors were transformed to Pichia pastoris KM71 and Bacillus subtilis WB600, respectively. The results showed that alpha-CGTase activity in the culture media of recombinant P pastoris was only 0.2 U/mL, while it was 1.9 U/mL in recombinant B. subtilis. In addition, we optimized the culture conditions of the recombinant B. subtilis strain. After cultivation at 37 degrees C for 24 h with shake flask, the CGTase forming activity in culture media reached to 4.5 U/mL (hydrolysis activity was 3200 IU/mL), which is 9.8-fold to that of the original strain P. macerans. PMID- 20352974 TI - [Effects of mixed carbon sources in cultivation of recombinant Pichia pastoris for polygalacturonate lyase production]. AB - In order to increase the production and productivity of alkaline polygalacturonate lyase (PGL), we studied the mixed carbon sources feeding strategies during the induction phase by recombinant Pichia pastoris GS 115. Glycerol, sorbitol or lactic acid co-feeding with methanol all enhanced the PGL production. Among all the feeding strategies, the sorbitol co-feeding strategy was most significant. By using this strategy, the PGL activity and productivity reached 1593 U/mL and 16.7 U/(mL-h). Compared to the control, the enhancements of PGL activity and productivity were 84.6% and 45.2% respectively, when we set the sorbitol feeding rate at 3.6 g/(h x L). PMID- 20352975 TI - [Expression of a pectin lyase A gene from Aspergillus niger in Pichia pastoris GS115]. AB - In this study, the mature peptide sequence of a pectin lyase gene A was amplified from Aspergillus niger strain EIM-6 by using RT-PCR reverse transcription technique. The cloned gene was then inserted into a Pichia pastoris expression vector pPIC9k to produce the recombinant expression plasmid pPIC9K-pelA. By using electric shocks, we successfully transformed the recombinant pPIC9K-pelA into Pichia pastoris GS115. The activity of the engineered strain reached to 2.3 U/mL after induction with the final concentration of 1.5% methanol. SDS-PAGE analysis revealed that the pPIC9K-pelA transformant had an additional protein band of approximately 38 kD, which was not present in the control. There were no significant differences between the recombinant and native pectin lyase with regard to their hydrolysis activities. PMID- 20352976 TI - [Investigation of micro-aqueous covalent immobilization of horseradish peroxidase by "conformation memory"]. AB - We has studied the feasibility of preventing protein from denature during covalent immobilization by "conformation memory", which was achieved by freeze drying under enzyme active conformation and cross-linked with carrier under micro aqueous media (MAM). Horseradish peroxidase (HRP) and chitosan beads have been used as the model enzyme and carrier. The MAM consisted of 99% dioxane and 1% water. We compared the immobilized HRP under MAM with that under traditional aqueous solvent, found that the optimum temperature of both was raised to 60 degrees C, and the optimum pH was 6.5. However, the MAM-immobilized HRP had shown less activity loss during usage and six times higher activity than that immobilized under aqueous solvent. After 30 min incubation at 70 degrees C, the MAM-immobilized HRP remained 75.42% activity while the aqueous-media-immobilized enzyme only 15.4%. The MAM-immobilized HRP has shown a better operation stability with 77.69% residue activity after 5 times of repeat operation while the aqueous media-immobilized enzyme only 16.67%. In addition, the MAM-immobilized HRP had also shown more advantages when used in phenol removal. We constructed enzyme electrodes (CS-HRP-SWCNTs/Au) to further display the different properties of the two immobilized HRP. MAM-immobilized HRP-electrode has shown two times stronger response signal to H2O2 than that immobilized under aqueous media, which indicated a better enzyme activity of MAM-immobilized HRP. Our research demonstrated that the conformation memory, to some extent, did contribute to preventing protein from denaturing when use HRP as a model, and it is feasible to immobilize enzyme by covalent cross-linking method under micro-aqueous media. PMID- 20352977 TI - [Effects of aqueous-organic solvents on peroxidase mimetic activity of Fe3O4 magnetic nanoparticles]. AB - We prepared Fe3O4 magnetic nanoparticles (MNPs) with the size of 10 nm by chemical coprecipitation. The effects of six aqueous-organic solvents, including tetrahydrofuran, dioxane, acetone, N, N-Dimethylformamide, methylalcohol, and Dimethyl Sulfoxide, on peroxidase mimetic activity of Fe3O4 MNPs were studied and compared with that of horseradish peroxidase (HRP). The relative activity of Fe3O4 MNPs droped sharply as the elevation of organic solvent concentration increased from 30% to 75% (V/V). In 15% organic solutions, the optimum activity of Fe3O4 MNPs was observed around 50 degrees C, under pH 3.6. After being treated at different temperatures and pH in 15% organic solutions, even under 75% concentration, Fe3O4 MNPs still preserved most of the activity when reacting in aqueous phase. The catalytic performances of Fe3O4 MNPs under given conditions were generally more superior to that of HRP. For it costs lower and it is easy to be prepared and segregated magnetically for recycle, to use the magnetic nanoparticles as a substitution for HRP has potential to be applied into organic catalysis. PMID- 20352978 TI - [Cloning and expression of Lactobaceillus reuteri glycerol dehydratase gene in Escherichia coil]. AB - There is growing interest in biodiesel and this results in the accumulation of glycerol. The exploitation and application of glycerol has attracted more and more attention. In the current study, glycerol was biotransformed to produce 3 hydroxypropionaldehyde by genetic engineering bacteria. It is known that 3 hydroxypopionaldehyde has been widely used as an important intermediate for chemicals, effective antimicrobial agent, and fix agent for tissues. A pair of primers was designed on the basis of the sequence of both NH2-terminus and the amino acid sequence of glycerol dehydratase reported by NCBI, and a fragment about 1.6 kb was obtained by PCR amplification using the total genome DNA of Lactobacillus reuteri as template, then the fragment was cloned to the pMD18-T vector and sequenced. Two specific primers were designed according to the obtained sequence, and a fragment with length of 1674 bp was amplified using PCR with these two specific primers. Consequently, the resulting products were digested with EcoR I and Hind III and ligated using T4 DNA ligase to the pET28b vector digested with the same enzymes. The recombinant plasmid, named pET28b dhaB, was transformed into E. coli BL21. The positive clones were induced with IPTG and the expression products were further analyzed by SDS-PAGE, indicating that protein with a molecule weight of around 65 kD was obtained. Furthermore, the glycerol dehydratase activity was evaluated and compared with the wild type strain as well. PMID- 20352979 TI - [Cloning and expression of organic solvent tolerant lipase gene from Staphylococcus saprophyticus M36]. AB - Lipases are important biocatalysts that are widely used in food processing and bio-diesel production. However, organic solvents could inactivate some lipases during applications. Therefore, the efficient cloning and expression of the organic solvent-tolerant lipase is important to its application. In this work, we first found out an organic solvent-tolerant lipase from Staphylococcus saprophyticus M36 and amplified the 741 bp Lipase gene lip3 (GenBank Accession No. FJ979867), by PCR, which encoded a 31.6 kD polypeptide of 247 amino acid residues. But the lipase shared 83% identity with tentative lip3 gene of Staphylococcus saprophyticus (GenBank Accession No. AP008934). We connected the gene with expression vector pET-DsbA, transformed it into Escherichia coli BL21 (DE3), and obtained the recombinant pET-DsbA-lip3. With the induction by 0.4 mmol/L of isopropyl beta-D-thiogalactopyranoside at pH 8.0, OD600 1.0, 25 degrees C for 12 h, the lipase activity reached up to 25.8 U/mL. The lipase expressed was stable in the presence of methanol, n-hexane, and isooctane, n-heptane. PMID- 20352980 TI - [Immobilized lipase-catalyzed synthesis of biodiesel from crude cottonseed oil]. AB - We investigated the transesterification of crude cottonseed oil with methyl acetate to biodiesel, by using Lipozyme TL IM and Novozym 435 as catalysts. Results showed that the biodiesel yield significantly increased with the addition of methanol into the reaction system, and the highest biodiesel yield of 91.83% was achieved with the optimum conditions as follows: n-hexane as solvent, molar ratio of methyl acetate to oil 9:1, 3% methanol based on the oil mass to inhibit the creation of acetic acid, 10% Lipozyme TL IM and 5% Novozym 435 as catalyst based on the oil mass, reaction temperature 55 degrees C and reaction time 8 h. Additionally, we explored the kinetics of lipase-catalyzed crude cottonseed oil to biodiesel, and proposed a kinetic model. PMID- 20352981 TI - [Optimize conditions and activities for neutrophil lipase immobilized by nano silica dioxide]. AB - We used adsorption method to immobilize the lipase by using nano-silica dioxide as the carrier. And we also studied different immobilization conditions effects on the catalytic activity. We got optimize immobilization conditions which were as follow the lipase quantity of 28,300 U/g, temperature of 45 degrees C, pH of 7.5 and treated for 10 h. Under these conditions the immobilized lipase activity yield 3867 U/g carrier. The best reactive temperature for immobilized lipase was 45 degrees C and higher than 5 degrees C for free enzyme, and the optimal pH dropped to 5.5 compared that of free enzyme (pH 7.0). The immobilized lipase stability for thermal and pH are improved than free lipase. When temperature was below 70 degrees C the immobilized enzyme activity was over 70% than initial activity. The free lipase activity just kept original 30% at 50 degrees C. When pH was 5-8, the immobilized lipase activity was still more than 50% and the free lipase only remained 20%. When we used the immobilized neutrophil lipase catalyzing different oil to produce biodiesel such as soybean oil, rapeseed oil and waste oil, the esterification rate of rapeseed oil was the highest. PMID- 20352982 TI - [Production of ligninase by co-fermentation of Coprinus comatus and Trichoderma reesei]. AB - In order to enhance the utilization efficiency, reduce the environmental pollution of traditional chemical treatment and the agriculture waste incineration; we studied the ligninase production by Coprinus comatus, Aspergillus niger and Trichoderma reesei through the plate screening. The results showed that C. comatus mixed culture with T. reesei have a good compatibility and higher yields of Laccase. On the basis of this pre-experiment, we studied the optimal conditions of mixed culture for enzyme production. Under the optimal conditions: the inoculation proportion of C. comatus and T. reesei (5:2), the interval of time (12 h), the temperature 260C, the shake rotation speed 150 r/min, fermented for 3 days, the Laccase activity reached 3267.1 U/mL, increased by 106% contrasted with single culture of C. commatus. PMID- 20352983 TI - [Cloning, heterologous expression and purification of a 3-ketosteroid-9alpha hydroxylase (KSH) from Mycobacterium sp. NwIB-01]. AB - 3-ketosteroid-9alpha-hydroxylase (KSH), a key enzyme in the microbial steroid degradation, is highly valuable for the production of some steroid drugs. Degenerate primers were designed by comparing the ksh from Rhodococcus erythropolis SQ1 and its homologous sequences in the reported genome of Mycobacteria. Subsequently, a gene fragment of KSH was cloned from Mycobacterium sp. NwIB-01, a sterol-transforming bacterium isolated from soil in our lab. According to the conservative sequence, the full-length 1188 bp gene encoding ksh (designated as M.S.-ksh) was obtained by chromosome walking, which showed 85% identity with the ksh of M. smegmatis mc(2)155. The heterologous expression of KSH was achieved in Escherichia coli BL21(DE3) using the pET-32a-c(+) vector system. The expressed KSH protein was mostly in soluble form after IPTG induction at 30 degreesC and accounted for more than 30% of total bacterial proteins according to SDS-PAGE electrophoresis. The molecular mass of KSH was about 45 kD, which was exactly the size predicted. After Ni2+ affinity chromatography, the purity of the target protein was more than 90%. Our work will definitely contribute to the industrial production of some steroid drugs by developing KSH genetically engineered bacteria. PMID- 20352984 TI - [Optimization of culture conditions for recombinant dextransucrase expression]. AB - We optimized the medium for recombinant dextransucrase expression in engineering strain Escherichia coli BL21 (DE3)/pET28-dexYG by an Orthogonal experiment. After the medium had been decided, we studied the effect of temperature, sucrose concentration and pH value on the yield. The results indicated that optimal conditions were adding IPTG of 0.25 mmol/L when OD600 reached 2.0 and cultivation lasted for 4 h at 25 degrees C. Under the selected medium and these conditions, the dextransucrase activity expressed by the engineering strain was high activity. Maximal activity reached 110.16 U/mL sucrose concentration effects the dextran yield grately. The results for dextransucrase expression would provide foundation for industrial application of dextransucrase. PMID- 20352985 TI - [Detection of sterigmatocystin based on the novel aflatoxin-oxidase/chitosan single-walled carbon nanotubes/poly-o-phenylenediamine modified electrode]. AB - A sensitive electrochemical biosensor based on Aflatoxin-Oxidase (AFO) was developed for detection of sterigmatocystin (ST). The enzyme was immobilized on chitosan-single-walled carbon nanotubes (CS-SWCNTs) hybrid film, which attached to the poly-o-phenylenediamine (POPD)-modified Au electrode. The fabricated procedures of the biosensor were characterized with atomic force microscopy (AFM), fourier transform-infrared spectroscopy (FT-IR), and electrochemical impedance spectroscopy (EIS). The cyclic voltammetric results of the biosensor indicated that AFO exhibited a surface-controlled and quasi-reversible electrochemical redox behavior with a formal potential of -0.436 V (vs. Ag/AgCl) in 0.1 mol/L PBS (pH 7.0), which resulted from the direct electron transfer between entrapped AFO and the underlying electrode. The enzymatic electrode exhibited an excellent electrocatalytic response to ST. The linear range of ST determination was from 10 ng/mL to 310 ng/mL with correlation coefficient of 0.997, the detection limit was 3 ng/mL (S/N=3), and the response time was less than 10 seconds. The apparent Michaelis-Menten constant (K(M)app) was estimated to be 7.13 micromol/L. The biosensor had the advantages of good repeatability and stability, remaining 85.6% of its original current value after storage at 4 degrees C for a month, and the RSD for 11 replicate determination of 20 ng/mL ST was 3.9%. This AFO/CS-SWCNTs/POPD/Au modified electrode showed high selectivity and sensitivity in real sample analysis, giving values of recovery in the range of 87.6%-105.5%. The proposed method can be applied to the determination of ST in real samples with satisfactory results. PMID- 20352986 TI - [Immobilization of Candida sp. lipase on resin D301]. AB - We immobilized Candida sp. lipase onto seven kinds of industrial adsorption and ion exchange resins. By determining the activity of each immobilized enzyme, the weakly basic anionic exchange resin of D301 showed the best results for the immobilization of Candida sp. lipase. Comparing the scanning electron micrographs of D301 with Novozym 435 (immobilized Candida antarctica lipase B from Novo Nordisk Corp.), we selected D301 as a carrier for the immobilization of Candida sp. lipase. And we pretreated the resin D301 with the bifunctional agent glutaraldehyde and crosslinked it with Candida sp. lipase. The optimal conditions for the immobilization of Candida sp. lipase were as follows: 8 mL of the amount of 5% glutaraldehyde solution, five hours of the time pretreated D301 with glutaraldehyde, 1.0 g/L the concentration of Candida sp. lipase used, pH of the phosphate buffered, 6.0 and 10 hours of time for immobilization, respectively. The activity of immobilized enzyme was over 35 U/mg and the efficiency of immobilization was around 3.5 Ul(mg x h). PMID- 20352987 TI - [Traditional experiences and modern cognition on primary processing of traditional Chinese medicinal materials]. AB - Primary processing is important links and closely related to the quality of traditional Chinese medicinal materials. The methods and technologies system of traditional primary processing were derived from the long-term practices and experiences, which is distinctive, colorful and diverse, and scientific, it is not only to cleaning of remove the non-officinal parts, drying for termination the physiological status of organisms, but also to retain the most active substances, decrease the toxic components, and promote the transformation among chemical ingredients through primary processing. So the traditional primary processing endowed with characters, quality, specifications and properties of traditional Chinese medicine, and embodied some important science truth. This paper analyzed the traditional experiences and modern cognition on primary processing of TCM materials based on the changes of chemical compositions and explored the scientific truth. These data may be providing foundation and support for process of normalization and standardization of primary processing of TCM materials. PMID- 20352988 TI - [Enhance technique researches on Glycyrrhiza industries, promote three dimensional rural economic development in three-north areas]. AB - OBJECTIVE: To analyze the current situation about Glycyrrhiza resources, summarize the research achievements on Glycyrrhiza relative industries, and indentify the importance of developing Glycyrrhiza industries to promote the three-dimensional rural economic development in the Three-North areas. METHOD: Literatures and documents were referred to, in combination with overview and analysis of the outcomes and achievements of our group. RESULT AND CONCLUSION: The gap between supply and demand of resources is enlarged continuously. To develop high-quality Glycyrrhiza cultivation is the most powerful and effective measure to protect wild resources and the environment and promote the three dimensional rural economic development in the Three-North areas. PMID- 20352989 TI - [Advancement of maggot including living body to treat chronic infected wounds]. AB - Human has used maggot to treat diseases for thousands of years. In recent years, with abuse of antibiotic and the rising incidence of antibiotic resistance, maggot therapy, as a surgical alternative, is mainly applied to treat chronic infected wounds on account of its low cost, efficacy and safety. Its mechanisms are disinfection, bio-debridement and enhancement of tissue regeneration. Maggot therapy which serves as a kind of biological therapy is promising. However, living maggot therapy could result in inevitable complications, so that we should apply traditional Chinese medicine theory to investigate and develop new delivery method of maggot. The review summarizes the past and present of maggot therapy. PMID- 20352990 TI - [Advances in studies on pharmacokinetics of scutellarin and scutellarein]. AB - Scutellarin is the major effective ingredient of breviscapine, which is widely used in the treatment of cardiovascular diseases and has a remarkable achievement. In recent years, more and more reseaches had focused on the pharmacokinetics of scutellarin and scutellarein. The article summarized the studies on pharmacokinetics of scutellarin and scutellarein have been performed by domestic and oversea scholars. PMID- 20352991 TI - [Radix isatidis and infectious diseases caused by viruses]. AB - Radix Isatidis (Banlangen in Chinese), used to clearing away heat and toxic material, is a traditional Chinese medicinal (TCM) herb. It is frequently used for preventing and treating infectious diseases caused by viruses. To provide scientific basis for the effect of Radix Isatidis on infectious diseases, the traditional effect and new research development on pharmacological activities are summarized in the review. According to the existed problems in the clinical application, the weak links and shortages of quality research and industrialized production of Radix Isatidis are discussed. It could present the new ideas for improving the technology of Radix Isatidis preparation, and promoting the rational use of the preparation in the clinical treatment. PMID- 20352992 TI - [Neuroprotective effects of curcumin]. AB - Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD). PMID- 20352993 TI - [ISSR analysis of genetic diversity of Coptis deltoidea]. AB - OBJECTIVE: To study the genetic diversity of Coptis deltoidea. METHOD: The genetic diversity of 90 individuals from 8 populations was analyzed by ISSR. RESULT: Twelve primers were selected to produce highly reproducible ISSR bands. Among 128 amplified bands, 94 showed polymorphism, the percentage of polymorphic bands reached 73.44%. Nei's gene diversity index (H) was 0.1925, Shannon's information index (I) was 0.3028, Gst was 0.7212. The genetic distance coefficient and similarity were 0.0858-0.2314 and 0.8046-0.9425, respectively. CONCLUSION: C. deltoidea held a high genetic diversity and the majority of genetic variation occurs among populations. By cluster analysis, the geographical distribution is very obvious. The ISSR marker can be used for the analysis of genetic diversity and genetic variation of C. deltoidea. PMID- 20352994 TI - [Genetic diversity of Changium smyrnioides based on SRAP]. AB - OBJECTIVE: To study the genetic diversity of Changium smyrnioides and give a reference for utilization of the germplasm. METHOD: Ten different populations of Ch. smyrnioides were analyzed by the approach of sequence-related amplified polymorphism (SRAP). Genetic similarity coefficient was calculated, and systematic relationships were constructed based on the UPGMA method. RESULT: Seventeen primer pairs were selected from 160. A total of 363 bands were scored, 314 bands of them were polymorphic and the average was 18.47 polymorphic bands per primer pair, which were up to 86.50% polymorphic ratio. The results indicated that there was abundant genetic diversity among the tested materials. Genetic similarity coefficient was ranged from 0.4959 to 0.8182. Cluster analysis showed that ten different populations of Ch. smyrnioides could be distinguished into two groups. CONCLUSION: High level genetic diversity was in different populations of Ch. smyrnioides, and genetic relationship was correlative to geographic position. PMID- 20352995 TI - [Characteristics of soil microbial variation during crop rotation period at cultivation area of Salvia miltiorrhiza in Zhongjiang of Sichuan province]. AB - OBJECTIVE: To study the characteristics of soil microbial variation during Salvia miltiorrhiza crop rotation. METHOD: the conventional cultivating microbial method was used to study the microbial number and communities structure and soil microbial biomass phosphorus (SMBP) was determined by chloroform vapor extraction method. The data was then analyzed by SPSS software. RESULT: With the increase of the crop rotation years, the numbers of bacteria and actinomycetes in soil also, but the fungi and SMBP decreased. CONCLUSION: Microbial mechanism of crop rotation of the planting S. miltiorrhiza is the regulation of microbial number and bacteria physiological communities, the process rebuilds the soil ecological system balance. Microbial communities in soil need at lest 2 years to get to restore, after planting S. miltiorrhiza, which consisting with traditional planting experience. PMID- 20352996 TI - [Differences of saikosaponin contents in Bupleurum chinense from habitats in Dongling Mountain & Wuling Mountain of Beijing]. AB - The different growing habitats of Bupleurum chinense were investigated in Donglin mountain & Wuling mountain areas, the saikosaponin a and d in samples of B. chinense collected from different habitats were determined by HPLC. Results showed that B. chinense distributed in various habitats, such as meadow, understory and brushy. Significant differences of saikosaponin contents were observed. The higher saikosaponins contents were showed in samples from meadow habitats, while the lower saikosaponins contents in samples from understory and brushy habitats. The ventilation situation and light condition showed positive correlation with the saikosaponins accumulation in B. chinense. It could be concluded that growing habitats play an important role in accumulation of saikosaponins in B. chinense. PMID- 20352997 TI - [Identification of corium stomachium galli by molecular taxonomy]. AB - OBJECTIVE: To establish a convenient and accurate method of DNA molecular marker for the identification of corium stomachium galli. METHOD: Cytb mtDNA sequences of Gallus gallus domestica and three other species of poultry were downloaded from Genbank. Species-specific PCR primers were designed according to the differential DNA fragments of the cytb genes. PCR tests were performed with the DNAs extracted from G. gallus domestica, three other poultry species and domestic mammal animals. RESULT: The specific primers of G. gallus domestica could only amplify the cytb mtDNA of G. gallus domestica. CONCLUSION: The primers are specific to G. gallus domestica mtDNA and can used to discern Corium stomachium from the false medicine. PMID- 20352998 TI - [Effect of water stress on content of four organic acids in different cultivated populations of Isatis indigotica]. AB - OBJECTIVE: To study the different and the variety of four organic acids in leaves of Isatis indigotica among different cultivated populations in water stress condition and healthy plant. METHOD: Four kinds of organic acids, such as oxalic acid, malic acid, ascorbic acid and citric acid from the leaves, were detected by HPLC. RESULT: Significant differences of four organic acids in the leaves of Beijing, Mongolia, Hebei and Shanxi cultivated populations. Compared with the healthy plant, the content of oxalic acid, malic acid and citric acid in water stress were increased, while the content of ascorbic acid was decreased. CONCLUSION: Contents of four organic acids can act as the guideline factor in I. indigotica because they were related with the water stress condition. PMID- 20352999 TI - [Preparation of submicron emulsion of fresh Zhongjiefeng volatile oil]. AB - OBJECTIVE: To prepare the submicron emulsion of fresh Zhongjiefeng volatile oil. METHOD: The Zhongjiefeng volatile oil submicron emulsion was obtained after passing the elementary emulsion through a high pressure homogenizer. The physical and chemical stability of the emulsion was evaluated with the stability parameter of centrifugation, appearance of emulsion and the pH. The formulation and processing factors were optimized by single factor reviewing and orthogonal experimental design. RESULT: By controlling various processing factors and optimizing formulation, the stable submicron emulsion of Zhongjiefeng volatile oil was prepared. Its mean particle diameter was 164-169 nm with PDI 0.084-0.107 and Zeta electric potential was -40 mV. CONCLUSION: The formulation and preparation technique of the emulsion is reasonable. PMID- 20353000 TI - [Optimized preparation of dry powder inhalation of Rehmannia glutinosa oligosaccharides by central composite design and response surface method]. AB - OBJECTIVE: To optimize the formulation of dry powder inhalation of Rehmannia glutinosa oligosaccharides (RGOS-DPI) extracted from traditional Chinese medicinal herbs. METHOD: RGOS-DPI was prepared by spray drying technique. Dependent variables such as yield, moisture absorption rate, emptying rate and mean diameter of micropowder were transformed into desirabilities mathematically by Hassan's method. Overall desirability was calculated from the geometric mean of the four desirabilities of each formulation. The effects of influence factors such as the inlet temperature, the contents of mannitol in the total amount of adjuvant and solution density were investigated using central composite design and response surface method. The data of overall desirability were analyzed using multi-linear equation and second-order polynomial equation for selecting the optimal conditions for DPI preparation. RESULT: The method of second-order polynomial equation was superior to multi-linear equation method in view of the correlation coefficients. Under the optimal conditions, the yield, moisture absorption rate, emptying rate and mean diameter of the RGOS-DPI were 78.60%, 5.93%, 94.20% and 2.537 microm, respectively. CONCLUSION: The central composite design can be used to optimize preparation. The optimized process for RGOS-DPI preparation is stable and feasible. The diameter of micropowder is suitable which can meet the demands of pulmonary delivery. PMID- 20353001 TI - [Study on in vitro mucosal permeation properties and factors affecting mucosal permeability of paeonol]. AB - OBJECTIVE: To study the in vitro mucosal permeation properties of paeonol and the factors that affect such permeability. METHOD: Bullfrog skin was selected as the permeation model, and the modified Franz diffusion cell was adopted to investigate the percutaneous adsorption in vitro. Content of paeonol was quantified by HPLC. Kinds of receiving solution, parts of bullfrog skin and impacts of drug concentration on percutaneous adsorption in vitro were systematically studied. RESULT: Percutaneous permeation of paeonol was to some extent affected by osmotic pressure and pH value of the receiving solution. Abdominal skin, lateral abdominal skin and dorsal skin, with the permeability coefficient form high to low, had great influence on the permeation of paeonol. There existed a good percutaneous permeation of paeonol. And the relationship between the cumulative permeability rate and time was coincided with the first order kenetical process. CONCLUSION: Take the in vitro abdominal skin of bullfrog as the permeation model, some similarities are revealed between in vitro percutaneous permeation of paeonol and mucosal adsorption. PMID- 20353002 TI - [Optimization of cataplasm matrix with face-centered design-response surface method]. AB - OBJECTIVE: To optimize the matrix formulation of cataplasm. METHOD: Face-centered design was used in the experimental design, and response surface was produced in quadratic polynomial after data fitting in order to explore the impacts of Sodium Polyacrylate, Carbomer and the cross-linking agent on stickiness of cataplasm, optimize the prescription of the cataplasm matrix and perform the evaluation analysis. RESULT: The multiple correlation coefficient (R2) and adjusted R2 in the fitting method using quadratic polynomial were 0.970 and 0. 952 (F = 53.953, P = 0.0001), respectively, and the model was significant different. The ratio of optimum proportion of Sodium Polyacrylate, Carbomer and the cross-linking agent in the matrix of cataplasm was determined, which was proved efficaciously. CONCLUSION: Face-centered design-response surface method is a simple method with good prediction result for the optimization of cataplasm matrix. PMID- 20353003 TI - Chemical constituents of Periploca forrestii and their cytotoxicity activity. AB - OBJECTIVE: To investigate the chemical constituents of the roots of Periploca forrestii and evaluate their cytotoxicity activities. METHOD: Silica gel column chromatography was employed for the isolation and purification of chemical constituents. The structures were identified on the basis of spectral data and the cytotoxicities of compounds 2-4 were investigated by several tumors cell lines including blood tumor (HL-60, CCRT-CEM), prostate tumor (PC-3, DU-145) and Melanoma (UACC-62). RESULT: Four compounds were isolated and identified as follows, lupeol-20(29)-en-3-nonadecanoate (1), peroiforoside I (2), 3beta,5beta,14beta-3OH-8beta-H-car-20(22)-enolide (3), perplocin (4). CONCLUSION: Compound 1 is a new lupane triterpene fatty acid ester. Compounds 2-4 showed notable cytotoxicity against all tumor lines. PMID- 20353004 TI - [Isoflavones from vines of Pueraria lobata]. AB - OBJECTIVE: To investigate the isoflavones from the vines of Pueraria lobata. METHOD: The compounds were isolated by column chromatography over silica gel and RP-C18, and purified by Sephadex LH-20 column chromatography and preparative TLC. The structures were elucidated on the basis of physico-chemical properties and spectral data. RESULT: Twelve compounds were isolated and identified as: 3' methoxydaidzein (1), formononetin (2), genistein (3), daidzein (4), daidzin (5), genistin (6), ononin (7), 5-hydroxyl ononin (8), calycosin (9), 6"-O-acetyl genistein (10), 6"-O-acetyl daidzin (11), puerarin (12). CONCLUSION: For the first time, compounds 9-11 were isolated from the genus Pueraria plant, and compounds 1, 3, 6-8 were obtained from the vines of this plant. PMID- 20353005 TI - [Lactone constituents of Saussurea involucrata]. AB - OBJECTIVE: To study the chemical constituents of Saussurea involucrata. METHOD: Compounds were isolated and purified by column chromatography, and their structures were elucidated by chemical and spectroscopic methods. RESULT: Eight compounds were yielded and identified as beta-sitosterol (1), dotriacontanoic acid (2), hexacosan-4-olide (3), (+)-11alpha, 13-dihydrodehydrocostuslactone (4), 8alpha-acetoxydehydrocostus lactone (5), zaluzanin C (6), 11,13beta dihydrozaluzanin C (7), 8alpha-hydroxy-11beta-11,13-dihydrodehydrocostuslactone (8). CONCLUSION: Compounds 2-7 were first isolated from S. involucrate. PMID- 20353006 TI - [Chemical constituents of Periploca forrestii]. AB - OBJECTIVE: To study the constituents of the stems of Periploca forrestii. METHOD: The compounds were separated and purified by silica gel column chromatography, recrystallization and high-performance liquid chromatography. The structures were identified by various spectroscopic methods. RESULT: Nine compounds were isolated and identified as 3-O-acetyloleanolic acid (1), 14-ursen-3-ol-1-one (2), taraxasterol (3), jacoumaric acid (4), periplogenin (5), 2alpha,3beta dihydroxyursolic acid (6), E-p-hydroxy-cinnamic acid (7), caffeic acid (8), proanthocyanidin A2 (9). CONCLUSION: All compounds except 6 were isolated from this plant for the first time, compound 4, 9 were obtained from the Periploca for the first time. PMID- 20353007 TI - [A quantitative method for simultaneous assay of four flavones with one marker in Radix Scutellariae]. AB - OBJECTIVE: To develop a quantitative method for simultaneously determining four flavones in Radix Scutellariae, by using one chemical standard substance. METHOD: The relative correction factors (RCF) of four flavones were determined by HPLC DAD. Within the linear ranges, the values of RCF at 274 nm of wogonoside, baicalein, and wogonin to baicalin, were 0.7467, 0.5638, 0.4351, respectively. And the contents of baicalin in 27 samples of Scutellaria baicalensis were authentically determined by the external standard method, and the contents of the three other flavones were calculated according to their RCF. The contents of these four flavones in the all samples were determined with the external standard method. RESULT: The RCF had a good reproducibility (RSD 0.66%-2.83%). No significant differences between the quantitative results by the above two methods were observed. CONCLUSION: It is a fast, convenient, and accurate method to determine multi-components especially when some authentic standard substances were unavailable. It can be used as a method to control the quality of Radix Scutellariae. PMID- 20353008 TI - [Determination of ellagic acid compounds in Euscaphis japonica by using UPLC]. AB - OBJECTIVE: To develop an ultra performance liquid chromatography (UPLC) method for simultaneous determination of five ellagic acids in Euscaphis japonica. METHOD: Analysis was carried out on an Acquity BEH C18 (2.1 mm x 100 mm, 1.7 microm) column at 40 degrees C eluted with acetonitrile-0.1% phosphoric acid aqueous solution as mobile phases in gradient elution. The flow rate was 0.2 mL x min(-1), and the detection wavelength set was monitored at 245 nm. RESULT: All calibration curves showed good linear relationship within test ranges (r >0.9997), and the overall recoveries were in the range of 97.2%-102.1%, with RSD less than 3.2% (n = 6). The overall RSD of precision test were less than 2.9%. CONCLUSION: The developed method was simple, rapid, accurate and reproducible, and can be used for the quality control of E. japonica. PMID- 20353009 TI - [Changes of lignans' content in stems of Schisandra chinensis]. AB - OBJECTIVE: To determine lignan content in the vine stem of Schisandra chinensis during 12 months and provide the scientific basis for the development and utilization of the resources. METHOD: Analysis was carried out on an Eclipse XDB C18 column eluted with a mixture of methanol-acetonitrile-water (43: 28: 29) as the mobile phase. The flowrate was 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. Schisandrin, deoxyschizandrin and schisandrin B were used as reference substance, and the external standard method was used. RESULT: The content of three constituents in the vine stem varied under different months. Schisandrin's maximum is 2.3 mg x g(-1) in December, minimum is 1.4 mg x g(-1) in April. A Deoxyschizandrin's maximum is 0.8 mg x g(-1) in November, minimum is 0.4 mg x g(-1) in March; Schisandrin B's maximum is 3.0 mg x g(-1) in January, minimum is 1.1 mg x g(-1) in April. CONCLUSION: The collection seasons for the vine stem of S. chinensis are autumn and winter. PMID- 20353010 TI - [Inhibitory effect on activated renin-angiotensin system by astragaloside IV in rats with pressure-overload induced cardiac hypertrophy]. AB - OBJECTIVE: To investigate the effect of astragaloside IV (As IV) on the activation of rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy. METHOD: Left ventricle hypertrophy was induced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats were given astragaloside IV 1.0 mg x kg(-1) and 3.3 mg x kg(-1) for 12 weeks, respectively. After treatment, the left ventricular mass index (LVMI)was calculated by morphometry methods. Plasma and cardiac tissue angiotensin II, and plasma aldosterone were measured by ELISA method. Gene expressions of ACE, AT1 and AT2 in cardiac tissue were detected by real time PCR. Protein expressions of AT1 and AT2 in cardiac tissue were detected by Western blot. RESULT: Compared with model rats, LVMI was decreased by astragaloside IV treatment. Biochemical results indicated that the contents of angiotensin II in plasma and cardiac tissue as well as aldosterone in plasma were all increased in abdominal aorta banding rats comparing with sham-operated rats, then, decreased by astragaloside IV treatment. Gene expressions of cardiac ACE was downregulated by astragaloside IV, however, gene and protein expressions of cardiac AT2 were upregulated by astragaloside IV. Both elevated gene and protein expressions of AT1 were not attenuated by astragaloside IV. CONCLUSION: Excessive activated rennin-angiotensin system in rats with pressure-overload induced cardiac hypertrophy is inhibited by astragaloside IV treatment. PMID- 20353011 TI - [Regulating effects of aquaporin 4 expression in LoVo cells by serum containing total anthraquinone in rheum]. AB - OBJECTIVE: To investigate the regulating effects of serum containing total anthraquinone in rheum on the expression of AQP4 in cultured LoVo cells in vitro. METHOD: Sixteen SD rats were randomly divided into 4 groups respectively treated with 0, 1.4, 2.5, 4.5 g x kg(-1) x d(-1) of total anthraquinone in rheum by intragastric administration. After 7 days of treatment, the rats were anesthetized and celiotomized to prepare the serum containing total anthraquinone in rheum. LoVo cells cultured in vitro were treated with different concentrations of total anthraquinone in rheum for 24 h. The expression levels of protein and mRNA of AQP4 IN LoVo cells were decided by Western blot and semiquantive RT-PCR. RESULT: Western blot and semiquantive RT-PCR showed that serum containing total anthraquinone in rheum prepared from rats treated with 4.5 g x kg(-1) x d(-1) of total anthraquinone in rheum could inhibit the expression of mRNA and protein levels of AQP 4 in LoVo cells (P<0.01). CONCLUSION: Serum containing total anthraquinone in rheum can inhibit both the transcription and translation of AQP4 gene, indicating that the regulation mechanism of rhubarb on the expression of AQP4 can be related to the cathartic effect of rhubarb. PMID- 20353012 TI - [Study on antiinflammatory effect of different chemotype of Cinnamomum camphora on rat arthritis model induced by Freund's adjuvant]. AB - OBJECTIVE: To study the antiinflammatory effects of naphtha from different chemotypes of Cinnamomum camphora and natural borneol on the rat arthritis model induced by Freund's adjuvant. METHOD: The arthritis model was induced by injecting Freund's adjuvant in rat voix pedis dermis and the rats were randomly divided into seven groups: normal control group, model control group, triptergium wilfordii control group, borneol chemotype naphtha group, camphor chemotype naphtha group, isocamphane chemotype naphtha group and natural borneol group. Rats of the triptergium wilfordii control group were given orally 8.1 mg x kg(-1) triptergium wilfordii for 35 days, rats of the normal control group and model control group were given same volume water, and rats of other groups were given 80 mg x kg(-1) corresponding drug. We observed the rat common condition, weighed the rat body weight weekly, measured the degree of swelling of voix pedis every 4 days, weighed the thymus and spleen on the end of life, and measured the contents of cell factor TNF-alpha, IL-2, and IL-6 in rat blood serum. RESULT: As far as the arthrosis degree of swelling and the contents of cell factor TNF-alpha, IL-2, IL-6 were concerned, rats of model control group were higher than normal control group, and rats of other drug groups were lower than the model control group. The order of inhibition ratios of the arthrosis degree of swelling from high to low principle was isocamphane chemotype naphtha group, camphor chemotype naphtha group, borneol chemotype naphtha group and natural borneol group. All medication administration teams evidently reduced the contents of the IL-2 and IL-6, and the inhibition ratios were higher than 38%. In the case of the contents of TNF-alpha and IL-2, all groups were not evidently different. In the case of inhibition of IL-6, camphor chemotype naphtha group was better than borneol chemotype naphtha group and natural borneol group, the latter was better than isocamphane chemotype naphtha group. As far as the weight, thymus index and spleen index were concerned, all medication administration groups were not different. CONCLUSION: The different chemotypes of C. camphora have anti-inflammatory effect on the rat arthritis model induced by Freund's adjuvant, but pharmacological activity and mechanism of action are different. The study points out the clinical curative effects of the chemotypes of the kindred medicinal plant are different, and please consider the difference of chemotype in clinical application. PMID- 20353013 TI - [Study of hepatic energy metabolism on rats by six cold property traditional Chinese medicines]. AB - OBJECTIVE: To investigate the common rule hepatic energy metabolism on rats by six cold property of traditional Chinese medicines (TCM). METHOD: The activities of Na+ - K+ - ATPase, Ca2+ - ATPase and SDH, the content of hepatic glycogen, and the mRNA expression of hepatic uncoupling protein 2 (UCP2) were measured after the rats and been administrated with water extracts of Radix Sophorae Flavescentis, Fructus Gardeniae, Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Radix Gentianae respectively at 6.0, 7.0, 8.4, 6.0, 7.0, 4.0 g x kg(-1) doses for 30 days, twice a day. RESULT: The activities of Na+ - K+ - ATPase, Ca2+ - ATPase and SDH were depressed significantly by six cold property TCM. The decreased tendency of SDH was observed by six cold property of TCM, while statistical significance was obtained in Cortex Phellodendri, Radix Scutellariae, Rhizoma Coptidis, Radix Gentianae. The increased tendency of hepatic glycogen content was found by six cold property TCM, while statistical significance was not obtained in six groups. The decreased tendency of the mRNA expression of UCP2 was found by six cold property TCM, while statistical significance was obtained in Radix Sophorae Flavescentis, Cortex Phellodendri, and Radix Scutellariae groups. CONCLUSION: The six cold property TCM have the good effects on hepatic energy metabolism by decreasing the activity of mitochondria SDH to reduce the production of ATP by decreasing the activities of Na+ - K+ - ATPase, Ca2+ - ATPase to cut down the consumption of ATP, by decreasing the mRNA expression of hepatic UCP2 to decrease the heat production. PMID- 20353014 TI - [Theanine affects sedative effect of pentobarbital sodium in ICR mice]. AB - OBJECTIVE: To evaluate the effects of theanine on sedative effects induced by pentobarbital sodium. METHOD: The locomotor activities of ICR mice induced by theanine (0.25, 0.5, 1.0, 2.0, 4.0 g x kg(-1)), pentobarbital sodium (5, 10 mg x kg(-1)) or the combination of both were determined with video-tracking system, and a novel index: Peripheral active time Peripheral time (PATP) was established. Hypnosis effect of combination of both was tested with right-reflex disappearance. RESULT: Compared with normal saline (74.52 +/- 20.4)%, theanine alone decreased this PATP in dose-dependent manner from (62.03 +/- 21.11)%, (56.44 +/- 21.69)%, (31.13 +/- 17.2)%, (25.06 +/- 10.03)% to (17.21 +/- 7.43)% (P>0.05, P<0.05, P<0.01, P<0.01 and P<0.01, respectively). Compared with pentobarbital sodium (5 mg x kg(-1)), between 0.25 g x kg(-1) and 1.0 g x kg(-1) theanine combined with that decreased peripheral PATP from (28.30 +/- 17.57)%, (30.64 +/- 17.21)% to (24.28 +/- 9.59)% (all P<0.01), and increased by 2.0 g x kg(-1) reversely (61.95 +/- 19.39)%. Compared with normal saline, pentobarbital sodium (10 mg x kg(-1)) and the combination with theanine decreased significantly PATP (all P<0.01). Compared with pentobarbital sodium (10 mg x kg(-1)), 0.25 g x kg(-1) theanine combined with that increased PATP [(25.37 +/- 13.68)% vs (10.08 +/- 7.98)%, P<0.01)] and 0.5 g x kg(-1), 1.0 g x kg(-1) theanine could depresse that increase [(14.56 +/-10.10)%, (8.24 +/- 4.08)% vs (10.08 +/- 7.98)%]. Total distance and peripheral active time showed the same or similar tendency in theanine alone or combination with pentobarbital sodium . Theanine enchanced hypnosis effect of pentobarbital sodium in dose-dependent manner. CONCLUSION: Theanine can affect the sedative effect of low dose pentobarbital sodium in bidirectional action style but not change the hypnosis effect. PMID- 20353015 TI - [Effects of puerarin on expression of apelin and its receptor of 2K1C renal hypertension rats]. AB - OBJECTIVE: To examine the change of puerarin on the expression of apelin and its receptor of the two-kidney, one-clip (2K1C) rats. METHOD: Tirty male Sprague Dawley rats were randomly divided into normal control group (C), model group (M) and puerarin group (P). The mean of carotid arterial pressure (mCAP), mean of left ventricular end diastolic pressure (LVEDP), and the weight ratio of left ventricular mass (left ventricle plus septum) to bodyweight (LVM/BW) were measured to evaluate the model of 2K1C renal hypertension. The concentrations of apelin in the plasma and left ventricle (LV) were measured with radioimmunoassay. Apelin mRNA and APJ mRNA expressed in the LV were examined by reverse transcription-polymerase chain reaction (RT-PCR). The peptides of apelin and APJ expressed in the LV were detected with immunohistochemistry (IHC). RESULT: Compared with C group, the mCAP, LVEDP and LVM/BW of M group were higher 36.58%, 333.8% and 20.24%, respectively (P<0.05, P<0.01, P<0.01). Compared with M group, LVEDP and LVM/BW of P group were lower 65.24% and 13.12%, respectively (both P<0.05). However mCAP was of no significant difference between these two groups. The levels of apelin-36 in the plasma and LV of M group were respectively higher 18.56% and 207.38% than those of C group (both P<0.05), while ones of P group were lower 24.21% and 49.40% than those of M group (both P<0.05). The expressions of apelin mRNA and APJ mRNA at left ventricle tissues of 2K1C rats were higher 77.66% and 119.00% (both P<0.05) than those of C group. The ones of P group were lower 27.40% and 45.66% than those of M group (both P<0.01). The IHC results indicate that the expressions of apelin and APJ peptides at left ventricle tissues of 2K1C rats were higher 129.51% and 154.1% (both P<0.01) than those of C group, respectively. Whereas the ones of P group were lower 65.36% and 62.87% than those of M group (both P<0.01). CONCLUSION: Through regulating apelin/APJ system puerarin has protective effect on the development of left ventricular hypertrophy by renal hypertension. PMID- 20353016 TI - [Effect of angelica polysaccharides co-erythropoietin on JAK2/STAT5 signal transduction pathway in hematopoietic stem/progenitor cells]. AB - OBJECTIVE: To investgate the signal transduction and regulation in erythropoiesis by angelica polysaccharides (APS) to clarify the mechanism for APS promoting hematopoiesis. METHOD: The mononuclear cells were isolated from foetus umbilic cord blood (mononuclear cells, MNCs), after MNCs were incubated in the presence of APS group (APS 200 mg x L(-1)) and control group for 24 h, the cells were stimulated with Epo (5 U x mL(-1)) for 0, 2, 5, 30 min, respectively. STAT5 was measured by ICC and laser confocal scanning microscope. JAK2, STAT5 in nucleus and cytoplasm were measured by western-blotting-ECL. RESULT: Angelica polysaccharide cooperated with Epo has significant impact on the expression of STAT5. The expression of STAT5 has significant difference between APS group and the control group at 4 time points. JAK2, STAT5 expressed in cytoplasm and nuclear of APS group significantly increased as compared to those of control group, and they expressed the strongest at 5 min. CONCLUSION: JAK2, STAT5 signal transduction molecule plays an important role in the effect of APS cooperated with Epo on promoting hematopoiesis. PMID- 20353017 TI - [Effect of total flavones of hawthorn leafon (TFHL) on expression of UCP2 in liver of NASH rats]. AB - OBJECTIVE: To study the expression of uncoupling protein 2 (UCP2) in liver of rats with nonalcoholic steatohepatitis (NASH) induced by fat-rich diet, and the effect of total flavones of hawthorn leafon (TFHL) on UCP2. METHOD: The NASH model of rat was induced by 12 weeks of fat-rich diet. Subsequently the rats were administrated with TFHL in accordance with 250, 125 mg x kg(-1) x d(-1) and the Essentiale N with 195.4 mg x kg(-1) x d(-1). The change of liver pathological. The levels of serum ALT and AST, the content of TG, CHOL, MDA and T-AOC activity of liver and were evaluated. The UCP2mRNA expression in liver was detected with RT-PCR, and the contents of UCP2 were examined with ELISA. RESULT: There are severe steatosis, inflammatory cellular infiltration in the liver of the NASH models. The levels of serum ALT, AST and the contents of TG, CHOL, MDA and UCP2 in the model group were higher than those of in the normal groop. The expression of UCP2mRNA was obviously enhanced and the activity of T-AOC decreased. The expression of UCP2 mRNA of rats was positively correlation with the contents of MDA, TNF-alpha. The inflammation activity in rat liver, the contents of MDA and UCP2, the expression of UCP2 mRNA in the administrated groups were obviously lower than those in the model group, while the activity of T-AOC was higher than that of model. CONCLUSION: TFHL may alleviate liver injury by means of the suppression of Oxidative stress/lipid peroxidation reaction and the overexpression of UCP2 in liver, which could prevent the further development of NASH. PMID- 20353018 TI - [WT inhibit human hepatocellular carcinoma BEL-7402 cells growth by modulating Akt and ERK1/2 phosphorylation]. AB - OBJECTIVE: To investigate effects of Akt and ERK1/2 signaling pathways on waltonitone (WT) induced cell growth inhibition in human hepatocellular carcinoma BEL-7402 cells. METHOD: Cell viability of BEL-7402 cells was examined using MTT assay. Phosphorylation of E Akt and RK1/2 were detected by Western blot analysis, while cell cycle distribution of BEL7402 cells was analyzed by flow cytometry. RESULT: WT could inhibit the BEL-7402 cells growth, induce the S-phase cell cycle arrest, activate Akt and ERK1/2 phosporylation. Moreover, the cell growth inhibition and S-phase cell cycle arrest induction of WT on BEL-7402 cells could be blocked by Akt and ERK1/2 inhibitors. CONCLUSION: WT induce the cell cycle arrest and inhibit the cell growth on BEL-7402 cells by modulating Akt and ERK1/2 phosphorylation. PMID- 20353019 TI - [Protective effect and mechanism of IPQDS on acute myocardial infarction in rats]. AB - OBJECTIVE: To observe the protective effect of Injection of Panax quinquefolium diolsaponins (IPQDS) and its mechanism on acute myocardial infarction in rats. METHOD: The acute myocardial infarct model was prepared by left anterior descending coronary occulusion for 24 hours in open chest anesthetized rats. The myocardial infarct size (MIS) was calculated. The activities of serum creatine hosphokinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the contents of malondialdehyde (MDA) and nitric oxide (NO) were determined. Blood was collected to observe low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity. At the same time, the platelet aggregation rate and platelet adherence rate were also determined. RESULT: In rats treated by IPQDS (in a dosage of 12.5, 25 and 50 mg x kg(-1) d, i.p. 3d ), the MIS was significantly reduced. The activities of serum CK, LDH and AST, and the content of serum MDA were declined. The activities of SOD and GSH-Px, and the content of NO were increased markedly. In addition, low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity as well as platelet aggregation rate were also declined significantly. But platelet adherence rate had no significant change. CONCLUSION: IPQDS has a protective effect on acute myocardial ischemia, which may be related to increasing activity of antioxidase in body, scavenging the damage of peroxidation from oxygen free radicals, decreasing the viscosity of blood and plasma and preventting thrombosis etc. PMID- 20353020 TI - [Mechanism study of protobioside on tumor cell proliferation]. AB - OBJECTIVE: To investigate the anti-proliferative effect of Protobioside on the HepG2 cells and its mechanism. METHOD: The inhibitory effects of Protobioside on 3 kinds of human cancer cell line was measured by MTT assay. Apoptotic morphological changes was observed by Hoechst33528 staining technique. Cell cycle were analyzed using flow cytometry. The expression of cell cycle related protein and apoptosis related protein were determined using Western blotting. RESULT: Protobioside shows strong cytotoxic power on HepG2 cells and IC50 were 20 micromol x L(-1). The nucleus became pyknosis at 36 hours. The cells in G2/M phase increase in a dose-dependent and time-dependent manner. And the protein level of CyclinB1 was down-regulated, that of Bax was up-regulated and that of Bcl-2 was down-regulated. CONCLUSION: The growth inhibition of Protobioside on HepG2 cells is highly related to cell cycle arrest at G2/M phase which was well correlated with the down-regulation of expression of Cyclin B1, and the induction of apoptosis via up-regulating of Bax and down-regulating Bcl-2 expression. PMID- 20353021 TI - [Review and reflection on study of four properties of traditional Chinese medicine]. AB - To summarize the biological effects of four natures of traditional Chinese medicine (TCM) in the recent 40 years, including cold, hot, warm and cool, which have the effect on central nervous system, endocrine system on the activity of sympathetic nerves, basal metabolic rate, the function of organs and tissues and secretion of cytokine out of body. And to review the new concepts and new hypotheses in recent 10 years which proposed on the four natures of traditional Chinese medicine. Based on the above summary we pointed out that the previous studies on biological effects have shortage in the following aspects: The studies had little connection with the TCM theory; The research highly concentrated on the biological effects of the cold and heat natures of drug; There is almost no research on the biological effects of the neutral nature; The research on the biological effects of the natures of traditional Chinese medicine had no combination with effects of drugs. And pointed out that studies on four natures of traditional Chinese medicine will be a multi-level, multi-disciplinary, multi factor, multi-targe research, connecting Chinese medicine theory. The research will be a combination of the macro research and the micro research, the qualitative research and the quantitative research and the experimental research and the clinical research. PMID- 20353022 TI - [Remarks on domestic clinical research status quo and improvement strategy from the evidence-based medicine]. PMID- 20353023 TI - [A multi-center randomized controlled trial on treatment of diarrhea-predominant irritable bowel syndrome by Chinese medicine syndrome-differentiation therapy]. AB - OBJECTIVE: To verify the clinical efficacy of Chinese Medicine syndrome differentiation therapy in treating diarrhea-predominant irritable bowel syndrome IBS-D. METHODS: With a blinded randomized controlled design adopted, 360 patients with IBS-D were randomly assigned to two groups, the treated group and the control group, they were treated with Chinese medicine and Pinaverium bromide for four weeks respectively. RESULTS: Comprehensive evaluation showed that the total effective rate in the treated group was higher than that in the control group significantly (93.8% vs 81.3%, P<0.01). Efficacy assessment on symptoms (by scoring) showed that the efficacy in the treated group was better than that in the control group in aspects of improving abdominal pain (86.1% vs 70.3%), defecation coziness (involving the frequency of defecation, incidence of tenesmus in the latest 10 days and Bristol typing of stool characters), living interfering, and total BSS score (P<0.05 or P<0.01). CONCLUSION: Chinese medicine syndrome-differentiation dependent therapy shows good efficacy in treating IBS-D. PMID- 20353024 TI - [Effect of jianpi tiaogan wenshen recipe in treating diarrhea-predominant irritable bowel syndrome]. AB - OBJECTIVE: To verify the efficacy of Jianpi Tiaogan Wenshen Recipe (JTWR) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) and to analyze its therapeutic mechanism through observing the effect of JTWR on clinical symptoms and rectal sensibility in patients. METHODS: With a prospective, randomized controlled trial adopted, 80 patients with IBS-D were assigned randomly equally and to two groups. The treatment group was treated with JTWR, and the control group was treated with pinaverium bromide tablet (PVB), all for four weeks. Patients' symptoms, such as abdominal discomfort, pain, and distension; frequency of defecation; appearance of stool; and occurrence of tenesmus were recorded before and after treatment by scoring, and the rectal sensitivity was detected as well. Patients with therapeutic effect of cured and markly effective were followed up four weeks after withdrawal of medication. RESULTS: Three cases in the treatment group and four cases in the control group were dropped. Except the appearing of mucus stool, no statistically significant difference was shown between the two group in all other symptoms, either at before or after treatment; but the end point scores of individual symptoms between pre- and post-treatment were different statistically in both groups (P<0.05). Per-protocol population set (PPS) analysis on comprehensive effect showed that the total effective rate and the cure rate in the treatment group was 81.1% (30/37) and 24.3% (9/37), and those in the control group, 80.6% (29/36) and 19.4% (7/36) respectively; while the full analysis set (FAS) showed a result of 80.0% (32/40) and 22.5% (9/40) vs 77.5% (31/40) and 17.5% (7/40) respectively, all with insignificant difference between groups (P>0.05). Follow-up study showed that relapse or aggravation of disease occurred in four cases in the treatment group and 12 in the control group respectively, showing significant difference between groups (P<0.01). Rectal sensitivity examination showed that the rectal thresholds of sensation, defecation, and maximum tolerable volume were improved in both groups after treatment (P<0.05), but showed no significant difference between groups (P>0.05). CONCLUSIONS: JTWR is effective in treating IBS-D, with the effect better than PVB in improving mucus stool, also in the remote effect. Its therapeutic mechanism is possibly by way of adjusting the sensitivity of rectum. PMID- 20353025 TI - [Relationship between Pi-Wei damp-heat syndrome with expressions of nuclear factor-kappaB mRNA and heat shock protein 70 mRNA in patients with chronic gastritis]. AB - OBJECTIVE: To explore the relationship between the genesis of Pi-Wei damp-heat syndrome (PDS) and the Helicobacter pylori (HP) infection in patients with chronic gastritis (CG) by observing the levels of nuclear factor kappaB (NF kappaB) mRNA and heat shock protein 70 (HSP70) expressions. METHODS: Gastric mucous membrane tissues collected through gastroscopy from gastric antrum of 51 CG patients, 36 of PDS type (CG-PDS) and 15 of Pi-qi deficiency syndrome (CG-non PDS) type, and 8 healthy persons (as control) were examined to diagnose the inflammation level with HE stain and to detect the existence of HP infection by rapid urease test and methylthioninium chloride stain. The mRNA expressions of NF kappaB and HSP70 in the tissues were determined quantitatively with FQ-PCR as well. RESULTS: Patients of CG-PDS showed higher level of HSP70 mRNA expression than in the control; and level of NF-kappaB mRNA expression was higher than that in the control and CG-non-PDS (all P<0.05); but both expressions were insignificantly different in CG-PDS patients with positive or negative HP infection (P>0.05). Positive correlation of the two expressions was shown in CG PDS with negative HP infection. CONCLUSION: NF-kappaB and HSP70 may partially embody, in some extent, the power of vital qi and evil qi in the organism; the over-expressed NF-kappaB and HSP70 may indicate the severe fighting between evil qi and vital qi, and both would be influenced to a certain degree in the fighting process. PMID- 20353026 TI - [Effect of er'zhi tiangui granule on metabonomics and level of Ca2+ in follicle fluid in patients after in vitro fertilization and embryo transfer]. AB - OBJECTIVE: To explore the mechanism of action of Er'zhi Tiangui Granule (ETG) in improving quality of oocytes by observing metabonomics and level of calcium ion in follicle fluid, and to investigate the impacts of calcium ion, cholinesterase (ChE) and creatinine (CCr) levels in human follicle fluid on the quality of oocytes and outcome of pregnancy in patients after in vitro fertilization and embryo transfer (IVF-ET). METHODS: Fifty-seven patients after IVF-ET were randomly assigned to two groups: the trial group (27 patients) and the control group (30 patients), both were treated with conventional Western medical treatment, but ETG and Liuwei Dihuang Granule (LDG) was given respectively to the two groups additionally. Changes of Shen-asthenia syndrome, amount of oocyte obtained, fertilization rate, cleavage rate, high-quality embryo rate and pregnancy rate, levels of calcium ion, ChE and Cr in follicle fluid, and metabonomics in the two groups were observed and compared. RESULTS: After treatment, scores of Shen-asthenia syndrome 8.30 +/- 1.46, fertilization rate 0.82 +/- 0.09, cleavage rate 0.97 +/- 0.07 and high-quality embryos rate 0.51 +/- 0.18 in the trial group were all better than those in the control group (9.16 +/- 1.15, 0.74 +/- 0.18, 0.91 +/- 0.10, 0.41 +/- 0.09, respectively, P<0.05); metabonomics principal component analysis showed that in the trial group, the principal component in follicle fluid distributed mainly in the section I, and that in the control group distributed mainly in the section II, showing significant difference between the two groups; while in most pregnant patients, it distributed in the section I. The Ca2+ concentration in the trial group was significantly higher than that in the control group (P<0.05). Levels of ChE and Cr in the trial group were higher than those in the control group, but the difference between them was insignificant. CONCLUSION: ETG is better than LDG in regulating metabonomics, Ca2+ concentration, improving the quality of oocyte and embryo, and increasing pregnant rate in patients after IVF-ET. PMID- 20353027 TI - [Study on application of SELDI protein chip technique in diagnosis of systemic lupus erythematosus of yin deficiency caused internal heat syndrome]. AB - OBJECTIVE: To investigate the application of surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI) protein chip in diagnosis and Chinese medicie syndrome type researching of systemic lupus erythematosus (SLE). METHODS: Eighteen female SLE patients of mild/moderate degree with yin-deficiency caused internal heat syndrome (YDHS) were enrolled in the treatment group, and 15 women healthy volunteers was set up as the control group. Using SELDI method, the pre-, mid- and post-treatment peripheral blood mononuclear cell (PBMC) protein fingerprint of them was created respectively, which was then managed to screen out the markers by using ZUCI-PDAS package for establishing a diagnosis model. RESULTS: Study was completed in 15 cases of the treatment group with 2 cases dropped out and 1 case lost. Before treatment, 44 protein peaks in the treatment group were found significantly different to those in the control group (P<0.01), and the sensitivity and specificity of the created models, 10542 Da m/z and 2554 Da m/z, reached 100%. After a 12-week treatment, 30 peaks were found significantly different between the two groups (P<0.01), and the sensitivity of 3365, 7104, 3882 and 6796 Da m/z created peak models was 100%, its specificity being 93.33%. Comparing the 35 samples (pre-, mid- and post-treatment) got from the treatment group with the 15 samples from the control group, significant difference was found in 55 peaks (P<0.01), the sensitivity and specificity of the 7103, 3882, 7143 Da m/z created peak models was 100% and 91.43% respectively. CONCLUSION: Significant differences of PBMC protein expression patterns were found between SLE patients of YDHS and healthy persons at times of before, during and after treatment, suggesting that SELDI may be used as a new method to create the diagnosis model, and its application in effecter protein screening, activity scoring and Chinese medicine syndrome type researching are expectable and waiting for further study in depth. PMID- 20353028 TI - [Effect of liangxue shengji recipe on incidence of post-percutaneous coronary intervention restenosis and adverse cardiovascular events]. AB - OBJECTIVE: To observe the intervention effect of Liangxue Shengji Recipe (LSR) on incidence of post-percutaneous coronary intervention (post-PCI) restenosis and adverse cardiovascular events. METHODS: With a randomized, single-blinded methods adopted, 100 patients with coronary artery disease (CHD) and underwent stent implantation were randomized into two groups, the control group and the treated group, conventional Western treatment was administered to them all, but with LSR to patients in the treated group additionally. They were followed up for at least six months. The incidences of post-PCI restenosis and adverse events, including cardiogenic death, acute myocardial infarction, recurrent angina pectoris, severe heart failure, further intervention and coronary artery bypass grafting, were observed to estimate the effect of LSR. RESULTS: No statistically significant difference between the two groups was shown in terms of incidences of intra-stent restenosis, recurrent angina pectoris, estimator of restenosis and its cumulative risk, as well as in reducing the incidence of single adverse event, but did show statistically significant difference between groups in reducing the incidence of united cardiovascular event (P=0.032) and its cumulative risk (P=0.036). CONCLUSION: Administration of LSR in post-PCI stage could significantly reduce the probability and cumulative risk of united cardiovascular events, and the beneficial effect presents at about six months post-PCI. PMID- 20353029 TI - [Effect of modified huanglian wendan decoction in treating senile patients with mild cognitive impairment of turbid-phlegm blocking orifice syndrome]. AB - OBJECTIVE: To observe the clinical efficacy of modified Huanglian Wendan Decoction (HWD) in treating senile mild cognitive impairment (MCI) of turbid phlegm blocking orifice syndrome. METHODS: With a block randomized, double blinded and controlled design adopted, the 64 patients of MCI selected from December 2007 to February 2009 were randomly and equally assigned to two groups. The treatment group was treated with HWD in dose of 200 mL, twice a day; the control group was given Aniracetam 0.2 g (for patients over 70-years-old, 0.1 g) three times a day. And the illusive medicine in dosage-form of capsule/decoction simulated to that used in the opposite group was applied. The medication and observation lasted for three months. Chinese medicine syndrome, cognition capacity (by MMSE), laboratory indexes [acetylcholine (Ach), superoxide dismutase (SOD), malondialdehyde (MDA)] and safety related indexes in patients were observed. RESULTS: After treatment, MMSE score increased in both groups, but the increment in the treatment group was significantly higher than that in the control group (P<0.01); Chinese medicine syndrome estimated by scoring showed that after treatment, all scores of syndromes, excepting the expectoration, were improved in the treatment group with the post-treatment scores significantly lower than those in the control group respectively (P<0.05 or P<0.01); while in the control group, lowering of scores only showed in some symptoms such as poor memory, heavy head or dizziness, and heavy sensation in limbs and body. Serum levels of Ach and SOD decreased and MDA increased in both groups after treatment, but the change of Ach was more significant in the treatment group (P<0.01). No obvious adverse reactions were found during the treatment. CONCLUSION: For treatment of MCI, HWD shows effects in improving patients' symptoms, cognition capacity and elevating serum Ach content better than that of Aniracetam; and with effects for raising SOD activity and reducing MDA level similar to those of Aniracetam. PMID- 20353030 TI - [Serum proteomic study on hypertension patients with Gan-Dan damp-heat syndrome]. AB - OBJECTIVE: To study the serum proteomics in hypertension patients with Gan-Dan damp-heat syndrome (GDDH) for tentatively find special proteins associated with the syndrome. METHODS: Study was performed in 60 hypertensive patients and 39 healthy persons as control. In the patients enrolled, 40 were differentiated as GDDH syndrome and the other 20 as non-GDDH syndrome. Their serum proteins were captured by weak cation nano-magnetic beads, and proteomic fingerprint was made by matrix assistant laser demodulation ionizing time-of-flight mass spectrometry (MALDI-TOF-MS) through mapping with protein chip reader type PBS II-C. After all the proteomic fingerprints being analyzed by Biomarker Wizard 3.1, the special expressed proteins for GDDH syndrome were identified by Biomarker Patterns Software 5.0 to create the syndrome decision model. RESULTS: Totally, 182 difference protein peaks between patients of GDDH and healthy persons (P<0.05); and 132 difference protein peaks between patients of GDDH and non-GDDH were detected (P<0.05). A decision model consisted 5 screened out protein peaks with mass-to-charge ratio of 2761.555, 6624.362, 2487.192, 2461.610 and 2744.318 was created, which could well differentiate the GDDH syndrome, with the sensitivity of 96.55%, specificity of 90%, false positive rate of 10% and false negative rate of 3.45%. Further blind test for prospective check showed its sensitivity being 81.82%, specificity 89.66%, false positive rate 10.34% and false negative rate 18.18%. CONCLUSION: The differently expressed protein is the material foundation of GDDH syndrome; molecular biological decision model established on the basis of this foundation can offer a tool for making Chinese medicine syndrome differentiation more objectively and accurately. PMID- 20353031 TI - [Effect of zishen shengxue recipe on endogenous erythropoietin in patients with renal anemia undergoing long-term hemodialysis]. AB - OBJECTIVE: To investigate the mechanism of Zishen Shengxue Recipe (ZSR) in treating renal anemia by observing its effect on serum level of endogenous erythropoietin in patients undergoing long-term hemodialysis. METHODS: Sixty renal anemia patients undergoing long-term hemodialysis were randomly and equally assigned to two groups. The treated group was treated with subcutaneous injection of erythropoiesis stimulating factor (rHuEpo) combined with oral intake of ZSR, and the control group treated with rHuEpo alone. They were observed for eight weeks, and the blood levels of endogenous human erythropoietin (Epo), hemoglobin (Hgb), hematocrit (Hct), as well as the residual renal function (RRF) in the two groups were compared. RESULTS: Serum Epo level in the control group was unchanged after treatment (P>0.05), while that in the treated group increased significantly, and showed significant difference in comparing with that in the control group (P<0.05). Levels of Hgb and Hct increased and RRF decreased in both groups (P<0.01), but the treated group showed higher increments and lesser decrement than those in the control group (P<0.05). CONCLUSIONS: ZSR can enhance the blood levels of Hgb, Hct and Epo, postpone the descent of RRF, and correct the anemic status in patients. Its mechanism of action is possibly through alleviating the inhibition of uremic toxin on erythropoiesis, in the meanwhile of promoting the secretion of Epo. PMID- 20353032 TI - [Effect of combined application of psoralen and ultraviolet A for inducing NB4 cell apoptosis and its impact on Fas/FasL gene expressions]. AB - OBJECTIVE: To explore the effect of combined application of psoralen (PSO, an extract from psoralea) and ultraviolet A (UVA) for inducing the apoptosis of human leukemic cell line NB4 and its impact on the Fas/FasL gene expressions. METHODS: According to factorial design, changes of apoptosis rate and ultrastructure of NB4 cells, as well as the gene and protein expressions of Fas/FasL were observed after cells were treated with PSO in different concentrations and irradiated by UVA of 360 nm wavelength for different times, using flow cytometry, transmission electron microscopy and quantitative polymerase chain reaction (PCR), and the outcomes were treated with variable analysis. RESULTS: (1) After treatment of PSO in concentration of 10, 20, 40, 80 microg/mL combined with a 5-min exposure of UVA, the NB4 cells apoptosis rate induced were 26.57% +/- 0.42%, 30.67% +/- 0.11%, 34.90% +/- 0.30% and 24.63% +/- 0.38% respectively. The effects were dose- and time-dependent, and an interaction was shown between the two actors. (2) After being treated by PSO plus UVA, obvious ultrastructure changes with apoptosis characteristics were shown in NB4 cell under electron microscope. (3) PSO plus UVA showed up-regulatory effect on gene and protein expressions of Fas, and down-regulatory effect on gene and protein expressions of FasL in a dose- and time-dependent manner, with the interaction between the two actors in altering Fas gene expression, also in altering FasL gene and protein expressions. CONCLUSION: Combined application of PSO and UVA can induce the apoptosis of NB4 cells, and the Fas/FasL system is one of the pathways for apoptosis inducing. PMID- 20353033 TI - [Effects of zilongjin on proliferation and apoptosis of human breast cancer cell line MCF-7]. AB - OBJECTIVE: To study the effect of Zilongjin (ZLJ, a composite Chinese drug) on proliferation and apoptosis of human breast carcinoma cell line MCF-7. METHODS: MCF-7 cells were randomly divided into four groups depending on the culture solution used, the control group, cultured with 1640 medium not contained ZLJ; and the three ZJL groups cultured with medium contained low (1.5 mg/mL), moderate (3 mg/mL) and high (6 mg/mL) dosage of ZLJ crude drug respectively. The changes of cell proliferation were assessed by cell growth curve assay and methyl thiazolyl tetrazolium (MTT) assay. And the cell apoptosis was analyzed by flow cytometry, Hoechst 33342 staining and DNA ladder assay. RESULTS: Compared with that in the normal control, the counts of cells in the three ZLJ groups were decreased significantly (P<0.05) at such time point as 24, 48, 72, 96, 120, and 144 h. Furthermore, apart from the comparison of the growth inhibition rate between the low and moderate dosage group at 24 and 72 h which were found to be no significant difference (P>0.05), the comparison f that among the three ZLJ groups appeared to be significant difference (P<0.05). The inhibitory effect of ZLJ on cell proliferation of MCF-7 was time- and dose-dependent; it could retard cells in G0/G1 cell phase; apoptosis of MCF-7 cell was induced by moderate and high dosage of ZLJ with revealing of apoptotic body and DNA ladder formation. CONCLUSION: ZLJ shows cell proliferation inhibitory and apoptosis inducing effects on human breast cancer cell line MCF-7, and thus to realize its anti tumor action. PMID- 20353034 TI - [Two cases of exothermic reaction induced by shenmai injection]. PMID- 20353035 TI - [Alteration of ion channel gene expression profile in rat model of post myocardial infarction heart failure]. AB - OBJECTIVE: To investigate the ion channel genes related with the genesis and development of heart failure after myocardial infarction through analyzing the differential gene expressions in non-infarcted myocardial tissues of post myocardial infarction heart failure (PIHF) rat model, and that of normal rat, and the bio-informatics Stc-GO analysis on them. METHODS: Rat model of PIHF was established by left anterior descending coronary artery ligation in six SD rats, and a control group with six sham-operative rats was set. Myocardial samples were taken in two batches from them (three rats in each group) at the heart failure formation stage and the stable stage (10 days and 8 weeks after operation) respectively. Total RNA extraction, probe preparation with reverse transcription, hybridization with double-channel cDNA microarray of rat's ion channel genes, and computerized differential gene expression screening were conducted, and Stc-GO functional clustering analysis was performed on the outcomes obtained to search out the GO sort of significance in them. RESULTS: At 10 days after operation, 319 common differential expressed genes were found from the 746 target genes, all of them were up-regulated. At 8 weeks after operation, in the 276 differential expressed genes, 274 were up-regulated while the other two down-regulated. The up regulated genes were those concerning receptors of various hormones, cytokines, neuro-hormones, growth factors and nuclear receptor, protein phosphorylase, G protein, various ion channels mediated by ligand or voltage, transport protein, receptor interfering protein, etc. The down-regulated genes concerning the potassium channel and transport protein, etc. Stc-GO analysis found that the six genes concerning adrenergic receptor kinase beta 1 (betaARK1), amiloride sensitive cation channel 2 neuronal (Accn2), voltage-dependent calcium ion channel gamma subunit 1 (Cacng1), cyclic nucleotide gated channel alpha 1 (Cnga1), Glutamate receptor ionotropic kainite 2 (Grik 2) and neurotrophic tyrosine kinase receptor type 2 (Ntrk 2), were all the significantly up-regulated differential genes of the model group related with the sham-operative group, and all showed a down-regulating trend as time goes on, and four genes in them were validated by the RT-PCR test. CONCLUSION: Ion channel genes concerning Accn2, Grik2, Ntrk2 and Cacng1 were up-regulated in PIHF, and its mechanism is waiting for further study. PMID- 20353036 TI - [Uniform designed research on the active ingredients assembling of Chinese medicine prescription for anti-liver fibrosis]. AB - OBJECTIVE: To explore the method and significance for studying active anti-liver fibrosis ingredients consisted Chinese medicine compound prescription based on Chinese medicine theory. METHODS: Optimized prescription was screened out, adopting uniform block design with 4-factor 8-level table and regression analysis, through applying the four known effective ingredients (cordyceps sinensis polysaccharide, salvianolic acid B, amygdaloside and gypenosides) of Fuzheng Huayu Capsule (FZHYC, a new Chinese medine anti-liver fibrosis drug) to two rat liver fibrosis models established separately by dimethylnitrosamine (DMN) and CCl4, and taking the liver content of hydroxyproline (Hyp) as the screen index. Then a further study for comparing and verifying the efficacy of the obtained optimized prescription was conducted on the two former models respectively by observing the changes of Hyp content in liver, serum ALT activity and fibrosis pathology after medication, controlled by the original FZHYC and the recipe assembled by all the four ingredients. RESULTS: Two optimized prescriptions (OPA and OPB) were screened out separately in the studies conducted on the two models. Both of them were consisted of cordyceps sinensis polysaccharide, Amygdaloside and Gypenosides, but different in constituent ratio, i.e., the ratio in OPA was 60 : 80: 50, and that in OPB, 20: 160: 50. Verifying study showed both OPA and OPA were significantly effective, with the efficacy equivalent to that of FZHYC (P>0.05). However, when they were used in combining with salvianolic acid B (the cutout ingredient in the screening), the efficacy lowered surely. CONCLUSIONS: Uniform design is a valuable method in the compatibility research of Chinese Medicine drugs' composition. To assemble a new compound recipe reasonably based on the prescription of traditional compound recipe could make its effect equivalent to that of the original prescription. Ingredients or constituents in a prescription, either presented synergistic or antagonistic effects, are not randomly stacked together, and they should be orderly assembled in intrinsic rules of qualitative and quantitative changing. PMID- 20353037 TI - [Study on the sensitizing potential of shuanghuanglian injection using popliteal lymph node assay in C57BL/6J mice]. AB - OBJECTIVE: To investigate the sensitizing potential of Shuanghuanglian Injection (SHL) by comparing the popliteal lymph node (PLN) response in mice induced by SHL and chemicals. METHODS: Sixty female C57BL/6J mice were equally and randomly divided into six groups, i.e. the blank control group (A) and five treated groups treated respectively with phenobarbital 1 mg/mouse (B), mercuric chloride ( HgCl2) 50 microg/mouse (C), D-penicillamine 2 mg/mouse (D), and SHL in low (1 mg/mouse) and high (5 mg/mouse) dosages (E and F) via subcutaneous injection into left pad of hind foot. Animals were sacrificed on the 8th day after injection, their bilateral PLNs were isolated and weighed respectively to calculate the PLN mass index (MI). Then the PLNs get from four mice in each group were fixed with 4% paraformaldehyde solution for histopathologic examination; the other six PLNs were prepared into single-cell suspensions to calculate cell index (CI) for comparing the changes of PLN in various groups. RESULTS: MI and CI in Group F reached to > or = 2 and > or = 5 (average) respectively, which was higher than those in Group A (P<0.05). Pathological examination showed that the left PLN in Group F enlarged, with remarkable germinal center and increased high endothelial venules proliferation. CONCLUSION: SHL could induce significant PLN response in C57BL/6J mice, suggesting it has certain sensitizing potential. PMID- 20353038 TI - [Effects of yinian jiangya decoction contained serum on endothelial cell proliferation and PPAR gamma mRNA expression in spontaneously hypertensive rat]. AB - OBJECTIVE: To observe the effects of Yinian Jiangya (YNJY) Decoction contained serum on cell proliferation of primary cultured endothelial cells of spontaneously hypertensive rat (SHR) and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression in the cells. METHODS: SD rats were fed with high-lipid diet and different doses (high, medium and low, containing crude drug of 5.2 g/mL, 2.6 g/mL, 1.3 g/mL respectively) of YNJY respectively and the serum contained different doses of YNJY (S-YNJY) was prepared by collecting the rats' serum after 20 days of feeding. The serum obtained from SD rats fed with normal diet, i.e. drug free serum (S-free) was taken for control. Primary cultured endothelial cells of SHR were treated respectively with S-YNJY in different doses (treated groups) and S-free (control group), the cell activity and the mRNA expression of PPAR-gamma in cells of all groups were detected by MTT and RT-PCR respectively at different time points: 2, 4, 8, 16 and 24 h after treatment. RESULTS: MTT test showed that at time points of 4 and 8 h, the OD value raised in the treated groups with insignificant difference among them (P>0.05), but was higher than that in the control group (P<0.05); at 16 h, it increased but showed a smaller increment in the medium-dose treated group (P<0.05); at 24 h, it decreased in all groups, but the decrement in the high- and medium-dose treated groups was more remarkable (P<0.05); at 48 h, it decreased continuously, with the decrement more significant in the high-dose group than in the control group (P<0.05). RT-PCR detection showed that at 4 h, the expression of PPAR-gamma mRNA was not changed significantly in all groups (P>0.05); at 8 h, it was remarkably lower in high-dose group than in others (P<0.05); at 16 h, it was higher in the three treated groups than in the control group (P<0.05), with a highest level shown in the high-dose treated group (P<0.01); at 24 h, the expression decreased in all groups, but the level in the low-dose treated group was still higher than that in the control group (P<0.05). CONCLUSIONS: YNJY Decoction shows a two-way regulation on endothelial cells proliferation, and which is negatively dose-dependent in the late stage. The regulation is perhaps relevant to the regulating of the PPAR-gamma mRNA expressions. The PPAR-gamma mRNA expression up-regulating and maintaining effects of YNJY Decoction may be one of the mechanisms for its vascular endothelial cell protection and blood pressure suppressing. PMID- 20353039 TI - [Protective effect of wenfei huayin recipe on lung of rats with chronic obstructive pulmonary diseases]. AB - OBJECTIVE: To explore the mechanism of Wenfei Huayin Recipe (WHR) in treating chronic obstructive pulmonary diseases (COPD). METHODS: The COPD model was induced by modified fumigating method and intra-tracheal instillation of lipopolysaccharide. Then reformed COPD model of cold-phlegm retention in Fei syndrome type. All the model rats were randomly divided into two groups, the model group and the treated group, treated respectively with WHR and saline for 14 successive days. Besides, a blank group without any intervention was set up for control. The general condition, weight growth rate, pathological changes of lung tissue under light microscope, ultrastructure under electron microscope, arterial blood gas analysis and levels of interleukin 4 (IL-4), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in lung homogenate by radio-immunity assay were observed. RESULTS: In the treated group, as compared with the control group, the symptoms of aversion to cold, swarming, wheezing, the degree of epithelial cell degeneration and necrosis, the inflammatory cell infiltration and the volume of cilia lodging, sloughing, and bullae of lung were lessened and weight growth rate was higher (P<0.01). Moreover, the treated group was superior to the control group in decreasing levels of PaCO2, IL-4, IL-8, TNF-alpha and increasing PaO2, IFN-gamma and IFN gamma/IL-4 ratio (P<0.01 or P<0.05). CONCLUSION: WHR can correct the Th1/Th2 imbalance and inhibit the inflammatory reaction, displaying an important role in improving the airway function and structure in COPD rats. PMID- 20353040 TI - [Effects of fuzheng huayu recipe in antagonizing rat's renal interstitial fibrosis]. AB - OBJECTIVE: To observe the effects of Fuzheng Huayu Recipe (FHR) on rat's renal interstitial fibrosis induced by mercuric chloride (HgCl2), and to explore preliminarily its mechanism of action. METHODS: Rats were randomly divided into four groups: the normal group, the model group, the FHR group and the vitamin E group, the latter two were treated respectively by FHR 4.6 g/kg and vitamin E 100 mg/kg. Rats model was established by oral administration of 8 mg/kg HgCl2 for 9 weeks. Serum creatinine (Cr) and urea nitrogen (BUN) content were tested with corresponding test kits; hydroxyproline (Hyp) content in kidney was assayed with hydrochloric acid hydrolysis; renal histologic change was observed with HE, Masson and methenamine silver (PASM) staining; and collagen type I (Col I), as well as protein expressions of fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) was determined with Western blot. RESULTS: Compared with the model group, the kidney/body weight ratio, serum levels of Cr and BUN, kidney Hyp content, and severity of renal interstitial fibrosis in the two treated groups were significantly lower (P<0.05 or P<0.01), and the improvements were more significant in the FHR group than those in the vitamin E group; Col I and FN protein expression was also weaker in the two treated group (Col, P<0.05; FN, P<0.01); while the expression of alpha-SMA was lower in the FHR group (P<0.01), but it wasn't in the vitamin E group (P>0.05). CONCLUSION: FHR could improve the HgCl2-induced renal function injury in rats, decrease extracellular matrix deposition and restrain renal interstitial fibrosis, the mechanism of action might be related with its inhibitory effect on myofibroblast activation. PMID- 20353041 TI - [Discussion on differences between efficacy and effectiveness in clinical evaluation]. AB - Both "efficacy" and "effectiveness" are two important concepts in clinical evaluation. In this article, the differences and relationship between the two connotations were expounded, and both the differences between "explanatory randomized controlled trial (ERCT)" and "pragmatic randomized controlled trial (PRCT)", which are respectively corresponding to "efficacy" and "effectiveness", and their application values in different stages in clinical therapeutic effect evaluation were further explored. This study may be a helpful reference for defining research purposes, locating appropriate research stages, and choosing suitable designs at its different stages in the clinical evaluation process of Chinese medicine researches. PMID- 20353042 TI - [Principle and application of Chinese medicine syndrome differentiation and disease classification]. AB - Taxonomy of diseases is usable in Western medicine and also in Chinese medicine, but with different measures of sorting, i.e. disease classification in Western medicine and the syndrome differentiation in Chinese medicine. Actually, an integrative mode of the above two measures is already the chief mode of sorting applied in clinical practice of Chinese medicine and integrative medicine. The two measures are introduced in this paper, and the integrative mode is deeply analyzed as well. Its biomedical interpretation and protocol are operational explained, and its important values, involving clinical practice for assessments of therapeutic efficacy, drug action and safety; new drug research and development; medical innovation; and research on internal relation among diseases, are discussed with illustration. The authors indicated that the integrative taxonomic mode of disease classification and syndrome differentiation is an important theoretical representation for mutual-supplementing of Chinese medicine and Western medicine in integrative medicine, also the important measure and approach for developing Chinese medicine and innovating biomedicine, and it is meaningful in both theoretical guidance and actual clinical practice. PMID- 20353043 TI - [Research of pro-/anti-inflammatory cytokines in the study of coronary heart disease]. AB - The study of the relationship between inflammation, inflammatory cytokines and coronary heart disease (CHD) has become a hot spot. The disequilibrium of pro- and anti-inflammation cytokines tempts the attention abroad and domestically, and this provides a new way to prevent and treat CHD in Chinese medicine. This paper discussed the research progress of pro- and anti-inflammatory cytokines in the study of CHD. PMID- 20353044 TI - [The density of information in English translation of Chinese medical terms and the translating strategy and method]. PMID- 20353045 TI - [Progress of integrative medical research on ulcerative colitis]. PMID- 20353046 TI - [Temporal change in annual air temperature and heat island effect in a coastal city and an inland city at mid-latitude in China during 1956-1998]. AB - Temporal changes in air temperature and urban heat island (UHI) effects during 1956-1998 were compared between a coastal city, Ji' nan, and an inland city, Xi' an, which were similar in latitude, size and development. During 1956-1978, except that the annual mean minimum temperature in Ji' nan increased by 0.37 degrees C x 10 a(-1), the temperature variables in the two cities did not display any apparent trend. During 1979-1998, all temperature variables of the two cities showed an increasing trend. Comparing with that in Ji' nan, the increasing rate of annual mean maximum temperature and annual mean temperature in Xi' an was greater, but that of annual mean minimum temperature was smaller. In the two cities, heat island effect occurred during 1956-1978 but without any apparent trend, whereas during 1979-1998, this effect increased with time, especially in Xi' an where the annual mean minimum temperature and annual mean temperature increased by 0.22 degrees C x 10 a(-1) and 0.32 degrees C x 10 a(-1), respectively. Both the level and the inter-annual variation of the heat island effect were much greater in Ji' nan than in Xi' an, but the increasing rate of this effect was greater in Xi' an than in Ji' nan. Obvious differences were observed in the increasing rate of annual mean maximum air temperature, annual mean air temperature, and annual mean minimum temperature as well as the heat island effect in Ji' nan, whereas negligible differences were found in Xi' an. Among the three temperature variables, annual mean minimum temperature displayed the most obvious increasing trend and was most affected by heat island effect, while annual mean maximum temperature was most variable inter-annually. Geographical location not only affected the magnitude of urban warming, but also affected the mode of urban warming and the strength of heat island effect. PMID- 20353047 TI - [Characteristics and numerical simulation of surface albedo in temperate desert steppe in Inner Mongolia]. AB - Based on the meteorological and biological observation data from the temperate desert steppe ecosystem research station in Sunitezuoqi of Inner Mongolia during growth season (from May 1st to October 15th, 2008), the diurnal and seasonal characteristics of surface albedo in the steppe were analyzed, with related model constructed. In the steppe, the diurnal variation of surface albedo was mainly affected by solar altitude, being higher just after sunrise and before sunset and lower in midday. During growth season, the surface albedo was from 0.20 to 0.34, with an average of 0.25, and was higher in May, decreased in June, kept relatively stable from July to September, and increased in October. This seasonal variation was related to the phenology of canopy leaf, and affected by precipitation process. Soil water content (SWC) and leaf area index (LAI) were the key factors affecting the surface albedo. A model for the surface albedo responding to SWC and LAI was developed, which showed a good performance in consistent between simulated and observed surface albedo. PMID- 20353048 TI - [Spatiotempaoral distribution patterns of photosynthetic photon flux density, air temperature, and relative air humidity in forest gap of Pinus koraiensis dominated broadleaved mixed forest in Xi-ao Xing' an Mountains]. AB - A continuous measurement of photosynthetic photon flux density (PPFD), air temperature, and relative air humidity was made in the forest gap in primary Pinus koraiensis-dominated broadleaved mixed forest in Xiao Xing' an Mountains to compare the spatiotemporal distribution patterns of the parameters. The diurnal maximum PPFD in the forest gap appeared between 11:00 and 13:00 on sunny and overcast days. On sunny days, the maximum PPFD during various time periods did not locate in fixed locations, the diurnal maximum PPFD occurred in the canopy edge of northern part of the gap; while on overcast days, it always occurred in the center of the gap. The mean monthly PPFD in the gap was the highest in June and the lowest in September, with the largest range observed in July. The maximum air temperature happened between 9:00 and 15:00 on sunny days, between 15:00 and 19:00 on overcast days, the locations were 8 m in the southern part of gap center both on sunny and overcast days. From 5:00 to 9:00, the air temperature at measured positions in the gap was higher on overcast days than on sunny days; but from 9:00 to 19:00, it was opposite. The mean monthly air temperature was the highest in June, and the lowest in September. The maximum relative humidity appeared between 5:00 and 9:00 on sunny and overcast days, and occurred in the canopy border of western part of the gap, with the relative air humidity on overcast days being always higher than that on sunny days. The mean monthly relative humidity was the highest in July, and the lowest in June. The heterogeneity of PPFD was higher on sunny days than on overcast days, but the heterogeneities of air temperature and relative humidity were not obvious. The maximum PPFD, air temperature, and relative humidity were not located in the same positions among different months during growing season. For mean monthly PPFD and air temperature, their variation gradient was higher in and around the center of gap; while for mean monthly relative humidity, it was higher in the edge of forest gap. PMID- 20353049 TI - [Environmental responses of four urban tree species transpiration in northern China]. AB - By using thermal dissipation probes (TDP), this paper monitored the sap flow of four tree species (Cedrus deodara, Zelkova schneideriana, Euonymus bungeanus, and Metasequoia glyptostroboides) at the Laodong Park in Dalian City from June to August 2008, and the soil moisture content and micrometeorological variables were mehsured simultaneously. Due to the absence of water-stress in the habitat, the sap flow of all sampled trees had no significant correlation with soil moisture content (R2 < 0.050, P > 0.211, n=1296). The correlation coefficient between solar radiation and sap flow reached 0.624-0.773 (P = 0.00, n=1296) despite the existing hysteresis. Solar radiation had major effect (R2 > 0.700, P < 0.05) during early morning (5:00-8:00) and late afternoon (18:00-20:00) when undergoing dramatic changes. As the main factor determining nighttime sap flow (R2 > 0.660, P < 0.05, n=1872), vapor pressure deficit (VPD) had a correlation coefficient as high as 0.650-0.823 (P = 0.00, n=1296) with the sap flow in whole-day scale. Meanwhile, the models constructed on the basis of VPD were able to explain 90% of daily sap flow change (P = 0.00). The correlation coefficient between sap flow and wind speed was relatively smaller than the previous two (R2 < 0.380, P = 0.00, n=1296), though showing significant correlation in affecting sap flow. Observations also detected the saturation phenomenon of sap flow to the environmental demands. PMID- 20353050 TI - [Effects of different type urban forest plantations on soil fertility]. AB - Aimed to study the effects of different urban forest plantations on soil fertility, soil samples were collected from eight mono-cultured plantations (Larix gmelinii, Pinus sylvestris var. mongolica, Pinus tabulaeformis var. mukdensis, Phellodendron amurense, Juglans mandshurica, Fraxinus mandshurica, Betula platyphylla, and Quercus mongolica) and one mixed plantation (P. sylvestris var. mongolica + F. mandshurica + Picea koraiensis + P. amurense + B. platyphylla) established in Northeast Forestry University's Urban Forestry Demonstration Research Base in the 1950s, with two sites of neighboring farmland and abandoned farmland as the control. The soils in broadleaved forest plantations except Q. mongolica were near neutral, those in mixed plantation, L. gmelinii, P. sylvestris var. mongolica, and P. tabulaeformis var. mukdensis were slightly acidic, and that in Q. mongolica was acidic. The contents of soil organic matter, total N and P, available P and K, and hydrolysable N tended to decrease with soil depth. There existed significant differences in the chemical indices of the same soil layers among different plantations. The soil fertility was decreased in the order of F. mandshurica > P. amurense > mixed plantation > J. mandshurica > B. platyphylla > abandoned farmland > farmland > P. sylvestris var. mongolica > L. gmelinii > Q. mongolica > P. tabulaeformis var. mukdensis, suggesting that the soil fertility in broadleaved forest plantations except Q. mongolica and in mixed plantation increased, while that in needle-leaved forest plantations tended to decrease. PMID- 20353051 TI - [Carbon emission from forest fires in Daxing' anling region in 2005-2007]. AB - Based on field investigation, the burned areas and consumed fuel loadings in Daxing' anling region caused by forest fires in 2005-2007 were estimated by comparing the normalized difference vegetation index (NDVI) before and after burning. The burned areas were classified with fire intensity, and the carbon emission from the fires was estimated by the fuel consumption and the average carbon content of plants. It was estimated that the total burned area was 436512. 5 hm2, of which, the severe, moderate, and light burned areas occupied 207178.4, 150159.2, and 79159.4 hm2, respectively. The consumed fuel loadings were 3.9 x 10(6) t in total, and the emitted carbon was 1.76 x 10(6) t, with 0.34 x 10(6), 0.83 x 10(6), 0.27 x 10(6), and 0.32 x 10(6) t from larch (Larix gmelini) forest, conifer and broadleaves mixed forest, broad-leaved forest, and grassland, respectively. PMID- 20353052 TI - [Comparison of seed oil physicochemical characteristics among three cultivars of Jatropha curcas L]. AB - Taking the cultivars Nanyou 1, 2, and 3 of barbadosnut (Jatropha curcas L. ) with different genotypes that can grow and seed normally at the inshore land in Hainan as test materials, the characters of their seeds and the physicochemical characteristics of their seed oils were analyzed and compared. No significant differences were observed in the seed length, width, thickness, and surface area among the cultivars, but Nanyou 2 had greater 1000 seed mass and lower unsound kernel percentage than Nanyou 1 and Nanyou 3, suggesting that the seed satiation of Nanyou 2 was good and the fecundity was excellent. The kernel oil content of Nanyou 3 was significantly higher than that of Nanyou 1 and Nanyou 2, and there was no significant difference between Nanyou 1 and Nanyou 2. The seed oil peroxide value, refractive index, and saponification value of the three cultivars had no significant differences, but the acid value for Nanyou 2 was much lower than that for Nanyou 1 and Nanyou 3. The seed oil iodine value of the three cultivars was all below 100, and was significantly lower for Nanyou 2 than for Nanyou 1 and Nanyou 3. The fatty acids in the three cultivars seed oils were mainly oleic acid, palmitic acid, linoleic acid, stearic acid, and margaric acid, and dominated by unsaturated fatty acids. The contents of saturated fatty acids in Nanyou 2 seed oil were relatively higher than those in Nanyou 1 and Nanyou 3 seed oils, indicating that comparing with Nanyou 1, cultivars Nanyou 2 and Nanyou 3 had relatively good potential for application. PMID- 20353053 TI - [Characteristics of soil seed banks in backwater area of Three Gorges Reservoir water-level-fluctuating zone at initial stage of river-flooding]. AB - A germination test was made to study the characteristics of soil seed banks in the backwater area (including the flooded, non-flooded, and control areas of secondary bush and abandoned farmland) of Three Gorges Reservoir water-level fluctuating zone. There existed significant differences in the soil seed banks between secondary bush and abandoned farmland, with an average seed density being 6991 +/- 954 seed per m2 and 26193 +/- 6928 seed per m2, respectively. Flooded area had the lowest seed density, while non-flooded area had the highest one. The seed density decreased with soil depth. A total of 118 species belonging to 45 families and 97 genera were detected in the soil seed banks of secondary bush and abandoned farmland, most of which were annual and perennial herbage species, belonging to Asteraceae, Poaceae, Scrophulariaceae, and Cruciferae. Among the 118 species, there were 34 species (occupying 28.8%) whose individuals accounted for less than 0.01% of the total. In the soil seed banks of secondary bush and abandoned farmland, the species number was similar, species diversity index and evenness index were relatively high, but the dominant species differed greatly, and the ecological dominance was relatively low. The species diversity in non flooded area and the ecological dominance in flooded area were the highest, and the similarity index between the flooded and non-flooded areas was the highest. PMID- 20353054 TI - [Leaf photosynthetic potential in canopy layers of un-thinned and thinned apple orchards]. AB - Through the comparison of leaf photosynthetic potential and of photosynthetically active radiation (PAR), leaf nitrogen concentration (Nl), and mass per unit leaf area (Ml) in different canopy layers of un-thinned orchard (UOD) and thinned orchard (TOD), this paper studied the effects of UOD rebuilding on the use efficiencies of PAR and nitrogen, and their relationships to the fruit yield and quality. Thinning obviously improved the radiation environment in canopy. The radiation distribution in TOD canopy was more uniformly than that in UOD canopy, and the invalid space with relative PAR (PARr) less than 30% in TOD approached to zero, while the minimum mean PARr in UOD was 17%, and the space under 0. 3 of relative canopy height was invalid. The leaf photosynthetic efficiency in TOD was notably improved. Comparing with that in UOD, the photsynthetic rate (Pn) at the middle and bottom of the canopy in TOD was increased by 7.8% and 10.2%, respectively. Meanwhile, the photosynthetic potential parameters such as maximum carboxylation rate (Vmax) and maximum electron transfer rate (Jmax) also increased remarkably in TOD. The leaf photosynthetic potential had significant correlation with Nl, and the Nl was strongly correlated with PARr. As a result, leaf photosynthetic potential and PARr could be estimated according to the spatial distribution of relative leaf nitrogen concentration (Nlr). PMID- 20353055 TI - [Effects of soil acidity on Pinus resinosa seedlings photosynthesis and chlorophyll fluorescence]. AB - Red pine (Pinus resinosa) is one of the most important tree species for timber plantation in North America, and preliminary success has been achieved in its introduction to the mountainous area of Northeast China since 2004. In order to expand its growth area in other parts of Northeast China, a pot experiment was conducted to study the adaptability of this tree species to varying soil acidity. P. resinosa seedlings were grown in soils with different acidity (pH = 4.5, 5.5, 6.5, 7.5, and 8.0) to test the responses of their photosynthesis and chlorophyll fluorescence parameters to soil pH levels, and the appropriate soil acidity was evaluated. Dramatic responses in chlorophyll a and b contents, Pn and chlorophyll fluorescence parameters (Fo, Fm, Fv, Fv/Fm, and phi(PS II)) were detected under different soil acidity (P < 0.05), with the highest chlorophyll content and Pn under soil pH 5.5, and significantly lower chlorophyll content and Pn under soil pH 7.5 and 8.0. The chlorophyll content and Pn were 41% and 50%, and 61% and 88% higher under soil pH 5.5 than under soil pH 7.5 and 8.0. The seedlings had a significant photosynthetic inhibition under soil pH 7.5 and 8.0, but the highest Fv/Fm and phi (PS II) under soil pH 5.5. Comparing with those under soil pH 7.5 and 8.0, the Fv/Fm and phi (PS II) under soil pH 5.5 were 8% and 12%, and 22% and 35% higher, respectively. It was suggested that soil pH 5.5 was most appropriate for P. resinosa growth. PMID- 20353056 TI - [Carbon sequestration of young Robinia pseudoacacia plantation in Loess Plateau]. AB - In order to understand the carbon sequestration of ecological forests in Loess Plateau, a comparative study was made on the organic carbon density (OCD) of soil, litter, and plant organs in an 8-year-old Robinia pseudoacacia plantation and nearby barren land. Comparing with the barren land, the young R. pseudoacacia plantation had a decrease (0.26 kg x m(-2)) of soil OCD, but the OCD in its litter, root system, and aboveground organs increased by 121.1%, 202.0%, and 656. 7%, respectively, with a total carbon sequestration increased by 3.3% annually, which illustrated that R. pseudoacacia afforestation on Loess Plateau had an obvious positive effect on carbon sequestration. PMID- 20353057 TI - [Carbon cycle in ten kinds of forest ecosystem in Guangzhou City]. AB - Based on an extensive collection of information and experimental data, this paper studied the carbon cycle in ten kinds of forest ecosystem in Guangzhou, China, aimed to explore the carbon cycling patterns in, southern subtropical forest ecosystems. For the test ecosystems, their carbon density ranged from 108.35 to 151.85 t C x hm(-2), with 10. 85-48.86 t C x hm(-2) in tree layer and 87.74-99.01 t C x hm(-2) in soil layer (0-60 cm), being lower than the national average. There were 4. 41-9. 15 t C x hm(-2) x a(-1) flowed from atmosphere to vegetation stratum, 0. 74-2.06 t C x hm(-2) x a(-1) from vegetation stratum to soil, and 3.94-5.42 t C x hm(-2) x a(-1) from soil to atmosphere, i.e., the forest systems absorbed 0.47-4.97 t C x hm(-2) x a(-1) from atmosphere. The net ecosystem production (NEP) varied with forest stand, being higher for broadleaved forest than coniferous forest, mixed forest than pure forest, and natural secondary forest than artificial forest. PMID- 20353058 TI - [Coverage extraction and up-scaling of sparse desert vegetation in arid area]. AB - Five kinds of remote sensing inversion models, i.e., linear spectral un-mixing model, sub-pixel un-mixing model, maximal gradient difference model, and two modified maximal gradient difference models, were used to derive f(c) from remote sensing data, and the results were compared with those measured in field, aimed to select appropriate model for deriving the data of the coverage of sparse desert vegetation in arid area. The virtual multi-scale coverage images were generated by using the simple mean scale extending method to verify the inversion information from MODIS data. It was shown that linear un-mixing spectral model had a higher precision than the other models, being applicable for deriving the data of the coverage of sparse desert vegetation, but the selection of end member was rather difficult and affected the application of the model. Sub-pixel un mixing model was universal, high precision could be obtained based on finely detailed vegetation map, but needed to measure lots of parameters. Maximal gradient difference model was simple and easy to perform, by which, the values of the coverage of crops and bare land predicted with the original model were close to the field-measured results, but the values of the coverage of sparse vegetation were underestimated. The results predicted by the modified three-band maximal gradient difference models were close to the field-measured values, and the inversed results of vegetation coverage under different scales were ideal, indicating that these models were reliable to effectively extract the information of the coverage of sparse vegetation in arid area. PMID- 20353059 TI - [Physiological differences and their genetic backgrounds of Erigeron breviscapus populations under enhanced UV-B radiation]. AB - A simulation experiment was conducted under greenhouse condition to study the effects of enhanced UV-B radiation (280-320 nm) on the flavonoid and MDA contents and antioxidant enzyme activities of six Erigeron breviscapus populations, and the intraspecific differences in physiology to the UV-B radiation. The related genetic backgrounds of E. breviscapus populations were also analyzed by ISSR analysis. Under enhanced UV-B radiation, the flavonoid content of E. breviscapus populations D01, D53, D63 and D65 increased significantly at seedling, flowering, and maturing stages, and the MDA content decreased significantly at seedling and flowering stages; while the flavonoid content of D47 and D48 increased significantly at flowering stage but decreased at maturing stage, and the MDA content increased significantly at the three growth stages. The POD and APX activities of D01 at the three growth stages, CAT activities at seedling and flowering stages, and SOD activity at flowering stage significantly increased; the SOD, CAT and APX activities of D47 at the three growth stages and the POD activity at maturing stage decreased significantly; the POD and APX activities of D48 at the three growth stages and the SOD activity at seedling and maturing stages decreased significantly; the SOD and APX activities of D53 at seedling and flowering stages and the CAT activity at flowering stage increased significantly; the SOD, POD and APX activities of D63 at the three growth stages increased significantly; and the CAT and APX activities of D65 at maturing stage had no significant changes, but the test enzyme activities at the three growth stages increased significantly. D01, D53, D63, and D65 were tolerant to UV-B radiation, while D47 and D48 were sensitive to UV-B radiation. The responses of E. breviscapus populations to enhanced UVB radiation varied with growth stage, being in the order of flowering stage > seedling stage > maturing stage. There was an obvious genetic polymorphism among the six E. breviscapus populations, which were divided into two groups at the level of 0.11 of genetic distance, one group including D01, D53, D63 and D65, and the other including D47 and D48. This classification was consistent with the results of physiological response index to UV-B radiation. PMID- 20353060 TI - [Soil enzyme activities in a Pleioblastus amurus plantation in Rainy Area of West China under simulated nitrogen deposition]. AB - From November 2007 to May 2009, a simulation test was conducted in a Pleioblastus amarus plantation in Rainy Area of West China to study the effects of nitrogen deposition on the activities of soil enzymes. Four treatments were installed, i.e., control (0 g N x m(-2) x a(-1)), low nitrogen (5 g N x m(-2) x a(-1)), medium nitrogen (15 g N x m(-2) x a(-1)), and high nitrogen (30 g N x m(-2) x a( 1)). Half year after N deposition, 0-20 cm soil samples were collected monthly, and the activities of peroxidase, polyphenol oxidase, cellulase, sucrase, urease, and acid phosphatase were determined. All test enzyme activities had apparent, seasonal variation, with the peak of cellulase, suerase, and acid phosphatase activities in spring, of urease activity in autumn, and of peroxidase and polyphenol oxidase activities in winter. Nitrogen deposition stimulated the activities of polyphenol oxidase, sucrase, urease, and acid phosphatase, inhibited cellulase activity, but had no significant effects on peroxidase activity. The test P. amurus plantation ecosystem was N-limited, and nitrogen deposition stimulated the decomposition of soil organic matter by microbe-enzyme system. PMID- 20353061 TI - [Effects of different ecological conditions on grain quality and RVA profile of japonica rice from Yunnan of China and Korea]. AB - Taking sixteen japonica rice varieties from Yunnan of China and Korea growing at three locations with different altitudes in Yunnan Plateau as test materials, this paper studied the effects of different ecological conditions on their grain quality, including brown rice length (BRL), brown rice width (BRW), length-width ratio (L/W), chalky rate (CR), whiteness (WH), amylose content (AC), protein content (PC), and alkali digestion value (ADV), and their starch RVA profile, including peak viscosity (PKV), hot viscosity (HTV), final viscosity (FLV), breakdown viscosity (BDV), setback viscosity (SBV), consistence viscosity( CTV), peak time (PeT), and pasting temperature (PaT). Of all the test parameters, SBV had the largest coefficient of variation. The coefficients of variation of BRL, CR, AC, PC, ADV, FLV, SBV, and PeT of Yunnan varieties were higher than those of Korean varieties, while the BRW, L/W, WH, PKV, HTV, BDV, CTV, and PaT of Korean varieties had higher coefficients of variation than those of Yunnan varieties. With increasing altitude, the BRL, BRW, L/W, WH, AC, ADV, FLV, and CTV of Yunnan varieties, and the BRL, BRW, WH, PC, PKV, HTV and BDV of Korean varieties decreased significantly, while the CR, PC, HTV, and PeT of Yunnan varieties, and the L/W, AC, ADV, SBV and CTV of Korean varieties increased significantly. The CR of Korean varieties had no obvious change. The PKV, BDV, and PaT of Yunnan varieties and the PaT of Korean varieties increased after an initial decrease, whereas the SBV of Yunnan varieties and the FLV and PeT of Korean varieties were in reverse. PMID- 20353062 TI - [Genetic characteristics of wheat functional leaves at filling stage under different water regimes]. AB - Taking one hundred and fifty doubled haploid (DH) lines of winter wheat cultivars Hanxuan 10 x Lumai 14 as well as their parents as test materials, the genetic bases of top three leaves length, breadth, and angle at mid-filling stage, and their correlations with yield traits were studied under two water regimes rainfed (drought stress, DS) and well-irrigation (WI) in 2005-2007. Under DS, the leaf length and width of DH lines and their parents were significantly lower than those under WI, whereas the leaf angle had a miscellaneous variation. Under the two water regimes, all the test traits of DH lines had a transgressive segregation, with the variation coefficients ranged from 5.1% to 45.9%. The heritability and gene numbers for the given traits showed great differences. Under WI and DS, the heritability of flag leaf angle (FLA) was the highest (91% and 97%, respectively), and that of the third leaf angle (TLA) was the lowest (23% and 31%, respectively). However, the gene number for FLA (4 and 2 under WI and DS, respectively) was the least, and that of TLA (21 and 25, respectively) in 2007 was the most. Interactive effects were observed among the genes controlling FLA, second leaf angle (SLA), and TLA under WI and DS, and controlling third leaf length (TLL) under WI. The grain number per spike and the grain weight per spike were positively correlated with the length and width of top three leaves, and the thousand-grain weight and the yield per plant were significantly correlated with TLL, FLA, and SLA, but all correlation coefficients were smaller ( < 0.481). It was suggested that the selection of top three leaves length and width should be carried out in the early generations of breeding procedure, while that of leaf angles should be carried out in advanced generations. An appropriate soil moisture regime retained in the critical growth period of the leaves would promote their growth and contribute to the grain yield. PMID- 20353063 TI - [Effects of high- and low temperature stresses on ascorbic acid metabolism system in potato leaves]. AB - In order to investigate the responses of ascorbic acid (AsA) metabolism system in potato leaves to high and low temperature stresses, a pot experiment was conducted with potato plants exposed to 40 degrees C or 5 degrees C, with the leaf AsA content, mRNA expression level of GalLDH and DHAR genes, activities of GalLDH, DHAR, APX, MDHAR and GR, and contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) determined. Under the exposure to 40 degrees C, the leaf AsA content increased rapidly and reached the highest (43.7% higher than the control) at 6 h, followed by a rapid decrease. Under the exposure to 5 degrees C, the AsA content also increased first, reached the highest (27.7% higher than the control) at 9 h, and then decreased. Under the two temperature regimes, the activities of leaf GalLDH, DHAR, APX, MDHAR and GR decreased after an initial increase, the mRNA expression level of GalLDH and DHAR genes showed the similar changes with their corresponding enzyme activities, and the leaf MDA and H2O2 contents increased remarkably after 24 h. All the results suggested that the AsA metabolism system in potato leaves was stimulated in the early period of high- and low temperature stresses, but its function declined gradually with the duration of the stresses. PMID- 20353064 TI - [Effects of ecological factors on the dough extensograph parameters of different winter wheat cultivars]. AB - In 2000-2001 and 2001-2002, six representative winter wheat cultivars Yumai 34, Gaomai 8901, Yumai 49, Yumai 70, Luoyang 8716, and Yumai 50 were consecutively grown at five locations (Xinyang, Zhumadian, Xuchang, Wuzhi, and Tangyin) with latitudes varying from 32 degrees N to 36 degrees N in Henan Province, aimed to understand the relationships of winter wheat dough extensograph parameters with genetic and ecological factors. The dough extensograph parameters were more affected by genetic factors than by ecological factors. Cultivars Yumai 34 and Gaomai 8901 had significantly higher maximum resistance and extension area than the other four test cultivars, and significant differences in the dough extensograph parameters were observed between the cultivars grown in the south region (Xinyang and Zhumadian) and in the north region (Wuzhi and Tangyin) of the Province. The change patterns of dough extensograph parameters with latitude differed in 2000-2001 and in 2001-2002, and the effects of climatic factors on the dough extensograph parameters varied with year. In 2001-2002, the precipitation at the stage from grain-filling to maturing affected the dough extensograph parameters significantly. Our results suggested that in order to improve the dough extensograph parameters of winter wheat, local meteorological conditions should be taken into full consideration in the soil water management at late-maturing stage. PMID- 20353065 TI - [Effects of different planting patterns on the senescence characteristics of flue cured tobacco roots and leaves]. AB - With flue-cured tobacco (Nicotiana tabacum) cultivar K326 as test material, a field experiment was conducted at Nanxiong area of Guangdong Province in 2008 to study the effects of four planting patterns, i.e., single-row ridge + film mulching at early stage, single-row ridge + film mulching at early and late stages, double-row concave ridge + film mulching at early stage, and double-row concave ridge + film mulching at early and late stages, on the senescence characteristics of its roots and leaves, and the economic traits of its leaves. Comparing with other three planting patterns, double-row concave ridge + film Aulching at early and late stages promoted the root growth of test cultivar during its whole growth period, with the root vigor increased significantly. Meanwhile, the leaf chlorophyll content and protective enzymes (SOD and POD) activities were higher, and the MDA content was lower. The leaf yield, output value, average price, and the proportion of superior leaves were also higher. Double-row concave ridge + film mulching at early and late stages alleviated the senescence characteristics of roots and leaves, and improved the economic traits of flue-cured tobacco leaves, being the efficient planting pattern to product high-quality flue-cured tobacco leaves in Nanxiong tobacco-growing area of Guangdong Province. PMID- 20353066 TI - [Effects of rotation and fallowing on the microbial communities and enzyme activities in a solar greenhouse soil under continuous cucumber cropping]. AB - A pot experiment was conducted to study the effects of rotation and fallowing on the microbial communities and enzyme activities in a greenhouse soil continuously cropped with cucumber and on the growth and yield of followed cucumber. Comparing with continuous cropping, rotation improved the components of soil microbial communities, which was manifested in the increase of bacteria and actinomycetes and the decrease of fungi. Rotation and fallowing enhanced the activities of soil invertase, urease, catalase, and polyphenol oxidase significantly. The quantities of soil bacteria and actinomycetes and the activity of soil invertase increased at the fruiting stage of cucumber plants, being the maximum at harvest stage, but decreased thereafter. In contrast, the quantity of soil fungi had a linear increase, and the activities of soil urease, catalase, and polyphenol oxidase decreased gradually during fruit development. Welsh onion and waxy maize promoted the growth and fruiting of the followed cucumber plants significantly, being the optimal rotation crops for cucumber. PMID- 20353067 TI - [Response of photosynthetic characteristics of peanut seedlings leaves to low light]. AB - To investigate the effects of shading and light recovery on the photosynthetic characteristics of peanut seedlings leaves, different shading treatments including no shading, 27% shading, 43% shading, and 77% shading were performed with black sunshade net at the seedling stage of two peanut cultivars Fenghua 1 and Fenghua 2, with related parameters determined. It was shown that with the increase of shading degree, the leaf chlorophyll content, actual PSII photochemical efficiency under irradiance (phi(PS II)), and maximum PS II photochemical efficiency (Fv/Fm) of test cultivars increased, while the Chl a/b ratio and photosynthetic rate (Pn) decreased. On the first day after light recovery, the Pn and stomatal conductance (Gs) decreased while the intercellular CO2 concentration (Ci) increased with increasing shading degree when measured under high light, but the Pn increased and the Gs and Ci decreased with increasing shading degree when measured under low light. The ratio of Pn measured under low light to that measured under high light increased significantly. With increasing shading degree, the light compensation point, light saturation point, CO2 compensation point, CO2 saturation point, and carboxylation efficiency decreased, while the apparent quantum yield increased. After the removal of shading, the Pn, phi(PS II), and Fv/Fm under natural light decreased immediately, but increased gradually 3-5 days after. 15 days after light recovery, the Pn, phi(PS II) and Fv/Fm in treatment 27% shading recovered to the level of no shading. As for the other treatments, the restored extent differed with shading degree and test variety. In the same treatments, the leaf chlorophyll content, Pn and phi(PS II) of Fenghua 1 were higher than those of Fenghua 2. The results demonstrated that shading at seedling stage improved the capabilities of test varieties in using low light, but reduced the capabilities in using high light. PMID- 20353068 TI - [Construction effect of fertile cultivated layer in black soil]. AB - The clayey farmland soil in black soil region of Northeast China, due to the existence of thicker plough pan created by unreasonable tillage, is a main limiting factor for local agricultural production. In this paper, a field experiment was conducted to study the construction effect of fertile cultivated layer on crop yield, soil physical properties, soil moisture content, and soil microbial number. After the construction of fertile cultivated layer, the soil had a thicker cultivated layer, and the crop yield was increased. Comparing with traditional tillage, applying straw and organic manure into 20-35 cm soil layer decreased soil bulk density by 9.88% and 6.20%, increased soil porosity by 9.58% and 6.02%, and enhanced soil saturated hydraulic conductivity by 167.99 and 73.78%, respectively, indicating that the construction of fertile cultivated layer could improve soil aeration and water permeability, and enhance the infiltration of rainfall. The soil moisture content and water use efficiency under the application of straw and organic manure into plough pan were higher than those under traditional tillage, and a positive correlation was observed between the moisture content in 0-35 cm soil layer and the emergence of maize seedlings. Due to the increased organic carbon source and aeration in the constructed fertile cultivated layer, soil microbial number was also increased. PMID- 20353069 TI - [Effects of high-yielding rice cultivar and cultivation pattern on methane emission from paddy field]. AB - A field experiment was conducted to observe the effects of high-yielding rice cultivars (early rice Luliangyou No. 996 and Chuanfeng No. 1, and late rice T you No. 259) and cultivation patterns (direct sowing and transplanting) on the methane emission from paddy field. The methane emission from early rice field before drying was 52%-73% of the total, while drainage and drying decreased the methane emission significantly. For late rice field, the methane emission during vegetative growth stage was 70% of the total. Under direct sowing of early rice, the average methane flux was lower, but the total methane emission was higher, compared with those under transplanting. As for late rice, both the average methane flux and the total methane emission were higher under direct sowing than under transplanting. There existed significant differences in the methane emission per unit grain production of early rice and late rice between direct sowing and transplanting. The methane emission per unit grain production under direct sowing of early rice super hybrid was increased by 4.84 g CH4 x kg(-1), compared with that under transplanting, and the emission under direct sowing of conventional early rice was increased by 3.48 g CH4 x kg(-1), compared with that under transplanting. The emission under direct sowing of hybrid rice was 6.67 g CH4 x kg(-1) higher than that under transplanting. In the same cultivation area and the same time period of direct sowing and transplanting, the methane emission was in the order of direct sowing of conventional early rice > transplanting of conventional early rice > direct sowing of early rice super hybrid > transplanting of early rice super hybrid, and direct sowing of late rice > transplanting of late rice. PMID- 20353070 TI - [Effects of exogenous NO on the growth and antioxidant enzyme activities of cucumber seedlings under NO3- stress]. AB - In this study, cucumber seedlings were cultivated in nutrient solution added with different concentration (0.05, 0.1, 0.2, and 0.3 mmol x L(-1)) sodium nitroprusside (SNP) as nitric oxide (NO) donor to study the effects of exogenous NO on the growth of cucumber seedlings and the activities of antioxidant enzymes in cucumber leaves under NO3- stress. Under the stress of 140 mmol x L(-1) NO3-, treating with 0.1 mmol x L(-1) of SNP for 1 d or 7 d increased the leaf soluble protein content and superoxidase (SOD), catalase (CAT), and ascorbic acid peroxidase (APX) activities, and decreased the leaf malondialdehyde (MDA) content significantly, suggesting that exogenous NO could enhance the capacity of cucumber seedlings in scavenging active oxygen species, protect the seedlings from the peroxidation of membrane lipids, and promote the seedlings growth and increase their resistance to high concentration NO3- stress. After the cucumber seedlings grew in 0.3 mmol x L(-1) of SNP for 7 d, the activities of leaf SOD, POD, and CAT decreased, and the MDA content increased, resulting in the injury of cucumber seedlings. It was indicated that certain concentration (0.1-0.2 mmol x L(-1)) exogenous NO could alleviate the NO3- stress to cucumber seedlings. PMID- 20353071 TI - [Effects of chemical ripeners on chlorophyll content and antioxidant enzyme activities of rapeseed pod]. AB - A field experiment was conducted to study the effects of ripeners Diguat and Roundup on the chlorophyll content, activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), cell membrane permeability, and malondialdehyde (MDA) content of rapeseed pods. Under effects of Diquat, the chlorophyll content decreased, while the activities of SOD, POD, and CAT, cell membrane permeability, and MDA content increased significantly, leading to the peroxidation of membrane lipid. These effects increased with increasing Diquat concentration. After treated with Roundup, the chlorophyll content had less change, activities of SOD, POD, and CAT increased slowly, and cell membrane permeability and MDA content had no obvious increase. With the increasing time of ripeners treatment, the activities of protective enzymes were inhibited to different degree, possibly due to the changes of molecular structure of antioxidant enzyme system under effects of the ripeners. PMID- 20353072 TI - [Microbial degradation of soil polycyclic aromatic hydrocarbons (PAHs) and its relations to soil bacterial population diversity]. AB - A laboratory simulation test was conducted to study the microbial remediation of soils contaminated by medium and low concentration polycyclic aromatic hydrocarbons (PAHs), and the relationships between the degradation of PAHs and the inoculated and indigenous microbes. The addition of high-effective PAHs degrading bacteria promoted the biodegradation of soil PAHs, and the effect was remarkable in the first two weeks. The biodegradation of test PAHs was phenanthrene < anthracene < pyrene < benzo [a] pyrene < chrysene, and negatively correlated with the diversity/abundance of soil bacterial population. In the same treatments, soil bacterial population structure varied less with time, and hence, to increase the activity of indigenous microbes would be an effective way to remediate the farmland soils contaminated by medium and low concentration PAHs. PMID- 20353073 TI - [Optimization of LCMSMS determination method for steroid compounds in wastewater and its application in feedlot wastewater]. AB - Taking Solid-Phase Extraction (SPE) as pre-treatment process, a laboratory experiment was conducted by adopting the technology of High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MSMS) to develop a method to determine the concentrations of 13 steroids in feedlot wastewater. Atmospheric Press Chemical ionization (APCI) source was applied and operated in negative ion model, with the parameters of Chromatography and Spectrometry being optimized. Quasi-molecular ion peak [M + H]+ appeared in the full scan of the first quadrupole of mass spectrometer (Q1) of Testosterone propionate and other 6 steroid compounds, while quasi-molecular ion peak [M + H-H2O]+ appeared in the full scan of Q1 of rest 6 steroid compounds. The linear range of the 9 points calibration curve for the 13 target compounds was determined to be from 1 to 1000 ng x ml(-1), and the calibration curve regression correlation coefficients (R) were always above 0.9990 for all sample batches. The average recovery rate of all target compounds was 83.75%-111.50%, and the methodological stability was determined to be acceptable, with the relative standard deviations between 2.02% 14.21% (n=6). Except that the limit of detection (LOD) of Mestradiol and Oestriol was higher than 15 ng x ml(-1), all the other target compounds had a LOD lower than 5 ng x ml(-1). In the determination of real samples from feedlot wastewater, the developed method represented a good profile to all target compounds at different concentrations in each stage of treatment. PMID- 20353074 TI - [Changes of soil enzyme activities in heavy metals polluted region: a case study in a wastewater-irrigated agricultural area near a smelter in Xinluo District of Longyan City, Fujian Province]. AB - Surface soil samples were collected from a wastewater-irrigated agricultural area near a smelter in the Xinluo District of Longyan City, Pujian Province, and their basic physical and chemical properties, activities of urease, cellulase, alkaline phosphomonoesterase, polyphenol oxidase and catalase, and contents of Cu, Cd, Pb and Zn were determined, aimed to approach the effects of heavy metals pollution and soil properties on the activities of soil enzymes. Correlation analysis showed that the total and available contents of soil Cu, Cd, Pb and Zn had significant positive correlations with the activities of soil urease, cellulase, alkaline phosphomonoesterase and polyphenol oxidase, but significant negative correlation with the activity of soil catalase. Soil pH had significant positive correlation with the activity of soil alkaline phosphomonoesterase, and soil silt content had significant negative correlation with the activity of soil catalase. Path analysis showed that Cu, Cd, Pb and Zn pollution promoted the activities of soil urease, cellulase and polyphenol oxidase, but had less effects on the activity of soil alkaline phosphomonoesterase. Soil available Cu, Cd, Pb and Zn didn't directly affect the activity of soil catalase, but indirectly inhibited it significantly. Soil physical and chemical properties had greater effects on soil enzyme activities, e.g., alkaline-hydrolyzable N directly inhibited the activity of soil urease, total P directly stimulated the activities of soil alkaline phosphomonoesterase and catalase and indirectly stimulated the activity of soil cellulase via available P, available P directly promoted the activity of soil cellulase but inhibited the activities of soil alkaline phosphomonoesterase and catalase, total K directly inhibited the activities of soil alkaline phosphomonoesterase and polyphenol oxidase, available K stimulated the activity of soil catalase via available P, and particle composition had significant effects on the activities of soil polyphenol oxidase and catalase. The above results demonstrated that because of the complicated and uncertain relationships between the contents of soil Cd, Pb, Zn and Cu and the activities of the five soil enzymes, it should be cautious to use the test enzyme activities to indicate soil heavy metals pollution. PMID- 20353075 TI - [Pollutant production and discharge from livestock and poultry industries and land carrying capacity in Zhejiang Province]. AB - Based on the investigation of pollutant production and discharge from a typical scale pig farm in Zhejiang Province at three pig growth stages (piglets, fattening pigs, and sows) in the autumn and winter 2007 and the spring and summer 2008, the coefficients of pollutant production and discharge from the pigs as well as the total annual pollutant production and discharge from the farm were estimated. In the meantime, the annual application amount of animal manure to the farmlands in Zhejiang Province was estimated by using these coefficients and the livestock and poultry inventories in Zhejiang Province in 2007. It was estimated that the total amount of applied animal manure in the Province in 2007 was 2106.8 x 10(4) t x a(-1), containing 13.57 x 10(4) t x a(-1) of N, 6.7 x 10(4) t x a(-1) of P, 0.11 x 10(4) t x a(-1) of Cu, and 0.20 x 10(4) t x a(-1) of Zn. The pig manure-equivalent farmland carrying capacity in the Province was 16.66 t x hm(-2) a(-1), and the average alarm limit was 0. 37. The application of animal manure in some areas of Zhejiang Province had exceeded the alarm limit for the land carrying capacity, and made a potential environmental threat. PMID- 20353076 TI - [Community structure of soil meso- and micro-fauna in different habitats of urbanized region]. AB - Investigations were made in May, June, and November 2007 and January 2008 to study the structural characteristics and their seasonal variations of soil meso- and micro-fauna communities in six habitats of three land use types (forest land, constructed grassland and farmland) in Tianhe District of Guangzhou City. The horizontal spatial distribution of soil fauna differed with habitat. During the investigation periods, the Botanical Garden of South China Agricultural University had the highest individual number (1286) of soil mesa- and micro fauna, while the farmland, especially in the Fenghuang Street area, had the lowest number of individuals and groups. The seasonal variation of the individual number was in order of autumn (1815) > spring (1623) > winter (1365) > summer (1276). Hierarchical clustering and detrended correspondence analysis also showed that the community composition of soil meso- and micro-fauna in different habitats exhibited distinct seasonal variation. In the same seasons, the community structure and composition of soil meso- and micro-fauna in different habitats were correlated to the degrees of human interferences and the properties of soil environment. PMID- 20353077 TI - [Community structure of rotifer in Mingzhu Lake of Chongming Island, Shanghai]. AB - A comprehensive survey on the quantitative distribution, community structure, species composition, dominant species, and species diversity of rotifer was conducted in the Mingzhu Lake of Chongming Island, Shanghai in January-December, 2008. There were 27 species of rotifer in the Lake, belonging to 8 families and 11 genera. The dominant species were Polyarthra trigla, Trichocerca pusilla, Brachionus calyciflorus, Brachionus forficula, and Philodina sp. The rotifer had an average annual density of (1505.42 +/- 1304.63) ind x L(-1), and an average annual biomass of (2.012 +/- 2.146) mg x L(-1). The Shannon-Wiener diversity index, evenness index, and richness index of rotifer community in the Lake were relatively low, while the dominance index was rather high, indicating that the community structure of the rotifer was unstable. The E/O value wes 1.61 +/- 1.46 on average, and the Q(B/T) values wes 1.23 +/- 0.84 on average. Water temperature was the main factor affecting the rotifer distribution. Biological assessment of water quality suggested that the Mingzhu Lake was on eutrophication. PMID- 20353078 TI - [Effects of starvation and refeeding in winter on the growth, survival, and biochemical composition of different size Ruditapes philippinarum]. AB - From December 2007 to April 2008, a laboratory experiment was conducted to study the effects of various starvation periods followed by the same refeeding period on the growth, survival, and biochemical composition of different size Ruditapes philippinarum at water temperature 3.0 degrees C-4.2 degrees C, salinity 25-27, and pH 7.90-8.16. No significant differences in the growth characteristics of R. philippinarum at low temperatures were observed among different size groups. The tolerance to starvation increased with increasing size, while the survival rate decreased with increasing starvation period, point-of-no return (PNR50) was not observed during the study period. For the larger size group (7 mm), the body moisture and lipid concentrations generally decreased with increasing starvation period. During starvation, the body protein content increased initially as a result of lipid being utilized for energy, but decreased thereafter when the lipid was depleting. Ash content remained unchanged during the study period, and was not affected by starvation or refeeding. PMID- 20353079 TI - [Effects of exoelectrogens and electron acceptors on the performance of microbial fuel cells]. AB - Two types of microbial fuel cells (MFCs) were adopted to analyze the effects of exoelectrogens and electron acceptors on the electrogenesis performance of MFCs. One was conventional MFCs inoculated with sewage and using nitrate as electron acceptor (S-MFCs), and the other one was modified MFCs inoculated with anaerobic treated wastewater and using ferricyanide as electron acceptor (A-MFCs). Exoelectrogens and electron acceptors had substantial effects on the acclimation period and the power output period of MFCs. The acclimation period was reduced from 500 h for S-MFCs to 430 h for A-MFCs, and the power output period was prolonged from 100 h for S-MFCs to 350 h for A-MFCs. The modified MFCs increased the removal of COD and the output of voltage by 25% and 300%, respectively. To select appropriate exoelectrogens and electron acceptors were crucial to the improvement of MFCs performance. PMID- 20353080 TI - [Evaluation of cultural service value of aquaculture pond ecosystem: a case study in a water conservation area of Shanghai]. AB - Pond aquaculture has existed in China for thousands of years, which has not only contributed great economic value, but also presented cultural value for human beings. With the development and upgrading of Chinese economy and culture, these values will be highlighted further. To evaluate the cultural service value of pond aquaculture ecosystem would provide a scientific base to the policy-making to avoid or reduce the wrong design-making or avoid the policy-malfunction, and also, to promote the development of aquaculture and related recreational fishing industry, increase the added value of aquaculture and the income of fish-farmers, and promote the economic development of rural area. Based on the survey data from the aquaculture ponds in the water conservation area of Dianshan Lake in Qingpu District of Shanghai and the related statistical data, the cultural service value including recreational value and existence value of the aquaculture pond ecosystem in the area was estimated by means of travel cost method (TCM) and contingent valuation method (CVM). The total cultural service value of this ecosystem was about 213 million Yuan x a(-1) or 231296. 69 Yuan x hm(-2) x a(-1), being 5. 25 times of the market value of aquaculture products, among which, recreational value was about 189 million Yuan x a(-1), and existence value was about 24 million Yuan x a(-1). It was suggested that in the construction of new rural areas of Shanghai, sufficient attention should be paid on the full play of the cultural service value of aquaculture pond ecosystem. PMID- 20353081 TI - [Wetland landscape ecological classification: research progress]. AB - Wetland landscape ecological classification, as a basis for the studies of wetland landscape ecology, directly affects the precision and effectiveness of wetland-related research. Based on the history, current status, and latest progress in the studies on the theories, indicators, and methods of wetland landscape classification, some scientific wetland classification systems, e.g., NWI, Ramsar, and HGM, were introduced and discussed in this paper. It was suggested that a comprehensive classification method based on HGM and on the integral consideration of wetlands spatial structure, ecological function, ecological process, topography, soil, vegetation, hydrology, and human disturbance intensity should be the major future direction in this research field. Furthermore, the integration of 3S technologies, quantitative mathematics, landscape modeling, knowledge engineering, and artificial intelligence to enhance the automatization and precision of wetland landscape ecological classification would be the key issues and difficult topics in the studies of wetland landscape ecological classification. PMID- 20353082 TI - [Spatiotemporal variations of crop radiation use efficiency and harvest index: research progress]. AB - The radiation use efficiency (RUE) model suggested by Monteith in 1972 is one of the most widely applied approaches for modeling net primary production and crop yield, especially by means of remote sensing techniques. To use this approach, RUE and harvest index (HI) are the two key parameters that need to be defined, besides the absorbed photosynthetically active radiation. However, there exist some problems in the studies and applications of RUE and HI. This paper reviewed the research progress on RUE and HI, summarized the current methods and procedures for defining RUE and HI values when using the RUE approach for predicting crop yield by remote sensing, and proposed that in order to maximize the effective application of RUE and HI in remote sensing crop yield and crop production management, future researches should seek proper procedures to determine the spatial heterogeneities of RUE and HI at regional scale based on field experiments. PMID- 20353083 TI - [Research progress in water eco-functional regionalization]. AB - Water eco-functional regionalization is a new zoning approach based on the study of regional differences in water ecosystem, aimed to reveal the spatial differentiation characteristics and distribution patterns of water environment at different regional and zonal scales. This paper discussed the methodologies, objectives, and limitations of water function zoning, water environmental function zoning, geoecology zoning, ecoregion classification, and water eco functional regionalization, summarized the research progress in the water eco functional regionalization, and compared the regionalization system at home and abroad. The disadvantages of our water eco-functional regionalization system were pointed out, and its development trend was prospected. PMID- 20353084 TI - [Effects of grape-replanting on soil bacterial and fungal populations]. AB - Rhizosphere and non-rhizosphere soil samples were collected from the vineyards having been planted for 3 and 30 years, and PCR-DGGE technique was adopted to study the effects of grape-replanting on the population structure and diversity of soil bacteria and fungi. The bacterial and fungal diversities were higher in 30-year-planted vineyard than in 3-year-planted vineyard, and higher in rhizosphere soil than in non-rhizosphere soil. After 30 years replanting, the population structure of bacteria and fungi approached the same in rhizosphere soil and non-rhizosphere soil but differed from that in fallow soil; while in the 3-year-planted vineyard, the population structure in rhizosphere soil was different from that in non-rhizosphere soil and fallow soil. Comparing with that in 3-year-planted vineyard, the rhizosphere soil microbial population in 30-year planted vineyard had a greater change. In bacterial population, Flavobacterium sp. (DQ339585) and Bacillus sp. (AY039821) decreased while Pedobacter sp. (AJ871084) increased; in fungal population, Omphalina farinolens (EF413029) appeared, Pestalotiopsis sp. (DQ657877, DQ657875, DQ657871), Phacidium lacerum (DQ470976), and Lecythophora decumbens (AF353597) decreased, while Pilidium acerinum voucher (AY48709) increased. Bacillus sp., Flavobacterium sp. , and Pestalotiopsis sp. had antagonism to pathogen, and their decrease reduced the resistance of grape against pathogen. The increase of Pilidium acerinum voucher might relate to the severe disease after grape-replanting. PMID- 20353085 TI - [Function of plant homeodomain-finger proteins in vernalization pathway in Arabidopsis and other cruciferous plants]. AB - Vernalization makes Arabidopsis and other cruciferous plants flowering earlier. During this process, an important plant homeodomain-finger(PHD-finger) protein named VIN3 is involved. The PHD domain was a conserved zinc-finger domain in eukaryotic organism. It used to take part in the interaction between proteins, especially the modification on histone of nucleosome, such as methylation, acetylation and phosphorylation. In vernaliazation pathway, the proteins translated by VERNALIZATION INSENSITIVE 3(VIN3) and homologous genes could result in methylation on H3K9 and H3K27 and deacetylation on H3K9 and H3K14 on chromatin histone of FLOWERING LOCUS C, a gene that inhibited flowering. The structure state of FLC would be changed from relaxation into compression. Then the transcription activity of FLC could be restrained and it couldn't inhibit flowering any more, so it would induce flowering earlier. This paper reviewed the function of PHD-finger proteins in vernalization pathway in Arabidopsis and other cruciferous plants, and overviewed the vernalization mechanism. PMID- 20353086 TI - [Ataxia-telangiectasia mutated gene and breast cancer susceptibility]. AB - Breast cancer is bound up with the environment. As a consequence of DNA damage induced by environmental carcinogens, a number of sophisticated sensing and transduction systems are initiated and the signal is conveyed simultaneously to multiple effectors. This process ultimately results in cancer. The protein kinase Ataxia-telangiectasia mutated (ATM) that encoded by ATM gene is the master regulator of DNA damage response. In this consecutive reaction, the protein kinase ATM responds to the DNA damage by phosphorylating a variety of downstream substrates, which plays an important role in the inhibition of the development of breast cancer. After ATM gene mutate, DNA damaged could not be accurately repaired and finally accelerates breast cancer transformation and proliferation. With the further research of ATM gene structure, function and breast cancer susceptibility, the extensive attention is paid to the relationship between ATM gene and breast cancer susceptibility. We reviewed the research advances in breast cancer susceptibility in several aspects of ATM gene, including mutation, polymorphism and methylation. PMID- 20353087 TI - [Characterization of M2 gene of H3N2 subtype swine influenza virus]. AB - M2 protein of influenza A virus is encoded by a spliced mRNA derived from RNA segment 7 and plays an important role in influenza virus replication. It is also a target molecule of anti-virus drugs. We extracted the viral genome RNAs from MDCK cells infected with swine influenza A virus (SIV) H3N2 subtype and amplified the SIV M2 gene by reverse transcriptase-polymerase chain reaction using the isloated viral genome RNAs as template. The amplified cDNA was cloned into a prokaryotic expression vector pET-28a(+) (designated pET-28a(+)-M2) and a eukaryotic expression vector p3xFLAG-CMV-7.1 (designated p3xFLAG-CMV-7.1-M2), respectively. The resulted constructs were confirmed by restriction enzyme digestion and DNA sequencing analysis. We then transformed the plasmid pET-28a(+) M2 into Escherichia coli BL21 (DE3) strain and expressed it by adding 1 mmol/L of IPTG (isopropyl-beta-D-thiogalactopyranoside). The recombinant M2 protein was purified from the induced bacterial cells using Ni(2+) affinity chromatography. Wistar rats were immunized with the purified M2 protein for producing polyclonal antibodies specific for it. Western blotting analysis and immunofluorescence analysis showed that the produced antibodies were capable of reacting with M2 protein expressed in p3xFLAG-CMV-7.1-M2-transfected cells as well as that synthesized in SIV-infected cells. We also transfected plasmid p3xFLAG-CMV-7.1-M2 into Vero cells and analyzed its subcellular localization by immunofluorescence. The M2 protein expressed in the Vero cells was 20 kDa in size and dominantly localized in the cytoplasm, showing a similar distribution to that in SIV infected cells. Western blotting analysis of SIV-infected cells suggested that M2 was a late phase protein, which was detectable 12 h post-infection, later than NS1, NP and M1 proteins. It would be a potential molecular indicator of late phases replication of virus. Our results would be useful for studying the biological function of M2 protein in SIV replication. PMID- 20353088 TI - [Cloning and functional analysis of the collectin gene from the grass carp Ctenopharyngodon idella]. AB - The grass carp (Ctenopharyngodon idella) collectin gene was cloned from mixed liver and kidney cDNA library. The full length sequence of grass carp collectin was 1128 bp, contained a 5' untranslated region of 229 bp and a 3' untranslated region of 104 bp. The open reading frame of grass carp collectin was 795 bp which could code a 264 amino acids polypeptide, including a terminal codon. Phylogenetic analyses showed that grass carp collectin shared the highest homology with that of zebrafish (Danio rerio). To understand the function of grass carp collectin, we expressed and purified the recombinant protein (P(CRD)) that comprised carbohydrate recognition domain (CRD). Agglutination of Aeromonas hydrophila and Staphylococcus aureus etc. and sugars inhibition experiments showed that: galactose, glucose, mannose and maltose could inhibit the agglutination of Aeromonas hydrophila. Maltose could lower the agglutination of Staphylococcus aureus, whereas peptidoglycan and glucose inhibited it well. In addition, the activity of grass carp collectin could not dependent on Ca(2+). PMID- 20353089 TI - [Preparation and bioactivity of anti-human red blood cell ScFv and CSFV E2 bifunctional fusion protein]. AB - The aim of this study is to construct a bifunctional fusion protein, which can conjugate both human red blood cells and antibodies against classical swine fever virus (CSFV). We respectively amplified 2E8ScFv and mE2 genes from different recombinant vectors, in which 2E8ScFv gene is the single chain Fv gene against H antigen of human red blood cells, whereas mE2 gene is the main antigen coding region gene of CSFV E2 protein. We used overlap extension PCR to obtain an artificial fusion gene segment 2E8mE2 containing genes of Both 2E8ScFv and mE2, then ligated into the expression vector pET-DsbA and expressed in Escherichia coli BL21(DE3) PlysS host cells, after induced with IPTG the target fusion protein was successfully expressed and identified in inclusion bodies by SDS-PAGE and Western blotting. We purified the fusion protein and renatured it from inclusion bodies to obtain a native state of well biological activity. The Erythrocyte agglutination test results indicated that the fusion protein can conjugate both human red blood cells and antibodies of CSFV. PMID- 20353090 TI - [Biotransformation of daidzein by resting cell system of bacterial strain isolated from bovine rumen gastric juice]. AB - In previous study we isolated a gram-positive bacterial strain, designated Niu O16, from bovine rumen gastric juice. The growing cells of bacterial strain Niu O16 is capable of biotransforming isoflavone daidzein into dihydrodaidzein efficiently under anaerobic conditions. In this study we investigated the optimal bioconversion conditions for the resting cells of bacterial strain Niu-O16 to convert daidzein into dihydrodaidzein. Single factor test showed that the optimal conditions for the initial pH of phosphate buffer, the concentration of the resting cell and the concentration of the substrate daidzein were 6.0-8.0, 32-64 mg/mL (wet weight) and 0.8-1.2 mmol/L, respectively. Orthogonal experiments were used to determine the optimal combination of the resting cell concentration, substrate concentration and biotransformation time. The results showed that the optimal combination included resting cell concentration 32 mg/mL, substrate concentration 0.8 mmol/L and the biotransformation time 24 h. Furthermore, the biotransformation kinetics under optimal conditions were studied, under which conditions the highest bioconversion rate was 63.9% in the resting cell system. The results might provide information for resting cell biotransforming of anaerobes as well as its industrial application. PMID- 20353091 TI - [Enhancing ethanol production using thermophilic yeast by response surface methodology]. AB - We optimized the conditions of simultaneous saccharification and fermentation (SSF) from cassava flour into high-concentration ethanol by thermophilic yeast GXASY-10. Based on the single factor experiment, we screened the important parameters by Plackeet-burman design. We used the path of steepest ascent to approach to the biggest region of ethanol production subsequently. Then, we obtained the optimum values of the parameters by Box-Behnken design. The results showed that the important parameters were the liquefaction time, glucosidase dosages and initial concentration of cassava flour (substrate). The optimum technical conditions were as follows: liquefaction time 35 min, glucosidase dosages 1.21 AGU/g substrate and initial substrate concentration 37.62%. Under such optimum conditions, the ethanol yield of 20 L fermentor reached 16.07% (V/W) after 48 h fermentation at 37 degrees C and 100 r/min. The ethanol content increased 33% than that under the original condition. PMID- 20353092 TI - [Molecular cloning and preliminary analysis of TaNOA in common wheat]. AB - Nitric oxide (NO) is an important signaling molecule with diverse physiological functions in both animal and plant cells. In this work, we isolated the full length cDNA and genomic DNA sequences of TaNOA-B1 encoding a putative NO associated (NOA) factor in common wheat. Bioinformatic analysis showed that TaNOA B1 possessed a similar intron/exon structure as its orthologous genes in Arabidopsis and rice. The amino acid sequence deduced from TaNOA-B1 was more than 60% identitical to those of Arabidopsis and rice NOA1 proteins. The primary structure of TaNOA-B1 contained the zinc finger and P-loop GTPase motifs conserved in Arabidopsis and rice NOA1 proteins. There existed at least three NOA gene members in common wheat, which were mapped to homoeologous group six chromosomes 6A, 6B and 6D, respectively. TaNOA-B1 investigated in this work was located on chromosome 6B. The transcripts of TaNOA members were found mainly in leaves. TaNOA-B1-GFP fusion protein may be located in mitochondria. TaNOA transcript level was up-regulated by abscisic acid (ABA) or NaC1 treatments, indicating that TaNOA might be involved in wheat responses to abiotic stresses. PMID- 20353093 TI - [Production of anti-recombinant human arrest defective 1 protein (hARD1) monoclonal antibodies for assaying human breast cancer tissues]. AB - Human arrest defective 1(hARD1) is an acetyltransferase catalyzing the N-terminal acetylation of proteins after translation. The high expression of hARD1 could be an indicator of the breast cancer. In current study, we produced an anti-hARD lp monoclonal antibody that could specifically recognize ARD1 in breast cancer tissues by using the immunohistochemical assay. The full-length His-tag hARD1 protein (1-235 aa) was over-expressed in Escherichia coli, and purified recombinant protein was injected into Balb/c mice to perform immunization procedure. Eight stable positive monoclonal cell lines were isolated. ELISA results demonstrated that all light chains of antibodies were kappa, and the heavy chains displayed three subtypes IgG1, IgG2a and IgG2b, respectively. A monoclonal antibody, which could specifically recognize hARD1 protein in breast cancer tissues, was identified by screening different cancer tissues using antibody-specificity method. Further, the specificity of the antibody was confirmed by Western blotting analysis. Our study would facilitate breast cancer diagnosis by using this ARD1 monoclonal antibody in clinic. Also, this antibody could be used as an important tool for further investigating the role of ARD1 in tumorigenesis. PMID- 20353095 TI - [Impact of different adjuvants on immunogenicity of the HBV particle vaccine containing the S + preS1 fusion antigen in Balb/C mice]. AB - We previous reported the development of novel hepatitis B virus(HBV) vaccine containing the surface antigen(S) plus PreS1 fusion derived from Chinese hamster ovary (CHO) cells system. In this study, we analyzed the impact of different adjuvants on immunogenicity of the HBV particle vaccine in Balb/C mice, including alum alone, CpG oligodeoxynucleotides (CpG-ODN) alone and CpG-ODN in combination with alum adjuvant. We first detected the antigen specific humoral response in mice, including total IgG antibody and IgG subtyping. Then, we characterized the specific cell-mediated immune (CMI) response by detection of gamma-interferon secreting splenocytes after stimulating with S or PreS1 peptide pool. Our results showed that: CpG-ODN adjuvanted vaccine could rapidly induce higher level of anti PreS 1 and anti-S antibodies, and a higher ratio of IgG2a/IgG1 antibody than that of alum adjuvanted vaccine. At the same time, CpG-ODN adjuvanted vaccine induced robust antigen-specific cellular immune responses in mice, which was superior to that of alum adjuvanted vaccine and CpG-ODN in combination with alum adjuvanted vaccine; however, the vaccine candidate with CpG-ODN in combination with alum adjuvant induced highest anti-S antibody and mixed IgG subclasses in mice after twice immunization. There exists dominant HBV CMI epitopes in the N-terminal of S antigen. These results provided important evidence that CpG-ODN adjuvanted HBSS1 particles vaccine may serve as a novel candidate in the development of new preventive and therapeutic agents against hepatitis B infection. PMID- 20353094 TI - [Construction and in vitro antiviral activity of highly effective artificial miRNA targeting to HIV-1 pol]. AB - RNA interference (RNAi) has exhibited huge potentials on anti-HIV-1 therapy research. The obtainment of RNAi element targeting to HIV-1 highly effectively and specifically was crucial for relevant research. Recent reports had described that microRNAs (miRNAs) posses more characteristics of inhibition and expression mechanisms than small interfering RNAs (siRNAs). In this study we explored the construction of artificial miRNA targeting to HIV-1 effectively and specifically. Sixteen siRNAs sequences were selected based on the conserved regions in the HIV 1 pol gene. ShRNA expression vectors were co-transfected with HIV-1 clone pNL4-3 to evaluate the abilities of siRNAs to inhibit HIV-1 expression. The pol1026 sequence was selected from candidates. The target sequence in the stem-loop structure of the well-characterized native miR-30a was replaced with pol1026 sequences, and the artificial miRNA expression vectors were co-transfected with the HIV-1 clone pNL4-3, results showed that HIV-1 can be effectively inhibited by miR-1026E. Target specificity of miR-1026E was confirmed by co-transfection assay with reporter plasmids containing different target sequences. The miR-1026E expression element was then inserted into Lentivirus which was used as a vector to transduce the MT-4 cells, MT-4-miR1026E expressing miR-1026E stably was cloned from transduced cells. The MT-4-miR1026E cell effectively inhibited HIV-1 replication in vitro. And the intracellular miR-181 and miR-16 expression levels and statl mRNA levels were not affected by the expression of miR-1026E in MT-4 miR1026E cells. miR-1026E is a promising candidate for future research. PMID- 20353096 TI - [Acute phase reaction of different macromolecule vascular grafts healing in rat muscle]. AB - To find out which biomaterial had the best biocompatibility, we compared the acute phase reaction of common biomaterials preparing for vascular grafts with the material of polyurethane modified by silk fibroin (SF-PU(1:1)). After transplanted the materials of dacron, polyterafluoroethylene (e-PTFE), polyurethane (PU), SF-PU(1:1) in rat muscle for one week, we studied the influence of different biomaterials on the histocompatibility by using rat acute toxicity test, test of local reaction in muscle, tissue section staining, WBC and PLT count. As a result, dacron had the worst histocompatibility. The other biomaterials had slight local inflammatory reaction. The WBC and PLT was nearly the same with the blank except dacron. e-PTFE, pure PU and SF-PU(1:1) had the better histocompatibility than traditional dacron. Especially SF-PU(1:1) had the best histocompatibility. Because of the better physical properties and histocompatibility of SF-PU( 1:1), the prospect of preparing small-diameter vascular grafts with SF-PU was cheerful. PMID- 20353097 TI - [Metabolic characteristics and kinetic model of recombinant CHO cells in serum free suspension batch culture]. AB - By using the cell density, cell viability, Pro-UK activity, specific consumption rate of glucose (q(glc)), specific production rate of lactate (q(lac)), yield of lactate to glucose (Y(lac/glc)) and as the evaluation indexes, the growth and metabolism characteristics of pro-urokinase (Pro-UK) expressing CHO cells in serum-free suspension batch culture were examined and compared to those in serum containing suspension batch culture. We observed hardly differences in growth and metabolism characteristics between the CHO cell populations grown in serum-free suspension batch culture and serum-containing suspension batch culture. The optimal mathematical model parameters for the CHO cells grown in suspension batch culture were obtained by non-linear programming of data representing the growth, substrate consumption and product formation of the CHO cells during logarithmic growth phase using MATLAB software, and the kinetic model of the cell growth and metabolism in serum-free culture were established. PMID- 20353098 TI - [Construction of a promoter reporter array for antibiotic screening]. AB - We designed and constructed an antibiotic screening system by using antibiotic responsive genes as reporters. Plasmid pCS26 carrying a promoterless luminescence reporter, luxCDABE, was used as the vector and the promoter regions of antibiotic responsive genes/operons from Escherichia coli were cloned upstream of the lux reporter to form the first part of the screening reporter array. Random promoter library of Salmonella enterica and Pseudomonas aeruginosa were screened for antibiotic responsive clones which consist of the second part of the screening array. The selected final reporter array responded to different antibiotics in distinct patterns and enabled in vivo high-throughput screening for antibiotics. Unknown antibiotics could, in general, be classified by analyzing the response patterns. This screening system is both sensitive and efficient and should prove to be a useful tool for screening new antibiotic compounds. PMID- 20353099 TI - [Immobilization of lipase labeled with fluorescent probe and its stability]. AB - The lipase labeled with the fluorescein isothiocyanat (FITC) was immobilized on the derivatives of the polyethylene glycol. The article discussed the effect of factors on the characters of lipase and analyzed the relationships among the activity of lipase, conformation, and fluorescence spectrum while the activity and the fluorescence spectrum of immobilized lipase were determined. The results demonstrated that polyethylene glycol 400-diacrylate could form appropriate network to improve the activity of enzyme. Adding ligand induced the lipase's catalytic conformation to increase the activity twice more than before. The active centre of lipase could be released by the extraction of ligand thus increasing the activity. After immobilization, the stability of labeled lipase improved greatly: immobilized lipases retained more than 70% and 60% of initial activity under conditions of 90 degrees C and strong acid or alkali, respectively. After immersing immobilized lipases into guanidine hydrochloride or urea for 15 days, the lipases retained upwards of 70% activity. The fluorescence spectrum could obviously reflect the changes of the activity and conformation of lipase. The fluorescence intensity was the minimum in the optimal pH and temperature. In the denaturing agent it declined as time passed. These results indicated that the unfolded processes of immobilized lipases are different under different conditions. PMID- 20353100 TI - [Cloning and expression of lipase gene to enantioselective resolution of (S) ketoprofen]. AB - We screened a strain NK13 for a certain extent asymmetric hydrolysis the rac ketoprofen Chloroethyl ester to (S)-Ketoprofen. As identified, NK13 was Bacillus megaterium. Digested NK13 genomic DNA with Sau3AI partially and recovered the fragment from 2 kb to 6 kb, cleaved the plasmid of pUC18 with BamH I, ligated the 2-6 kb fragment of NK13 genomic DNA into pUC18 plasmid, and then transformed an Escherichia coli strain DH5alpha. We created the gene library of NK13 and obtained a positive clone, pUC-NK1 in the library from the tributyrin flat. The result of sequencing showed that there was a whole open read frame (ORF) of 633 bp lipase gene in the plasmid of pUC-NK1. To compare with the genes of GenBank, this lipase gene was reported firstly (GenBank Accession No. EU381317). The lipase gene was amplified by PCR, using pUC-NK1 plasmid as template, and subcloned into the high expression vector pET21b(+) under the control of T7 promoter. The recombinant plasmid, pET-NKest1, was then transformed into an Escherichia coli strain BL21 (DE3) for the production of recombinant lipase protein. After 3 hours of induction by isopropyl-beta-D-thiogalactoside (IPTG), lipase was expressed. SDS-PAGE analysis showed that the relative molecular mass of the lipase protein was about 20 kDa. The result of high performance liquid chromatography (HPLC) showed that the conversion rate of the recombinant strain was fifty times than the wild strain NK13's. The (S)-Ketoprofen enantiomeric excess of the recombinant strain was 75.28%, which indicated that the lipase could hydrolyze (S)-Ketoprofen Chloroethyl ester firstly. If we research the conditions of the hydrolysis rac-ketoprofen Chloroethyl ester of this lipase further, maybe it could offer a foundation to product (S)-Ketoprofen industrially. PMID- 20353102 TI - [Construction of expression vectors for efficient expression of soluble recombinant proteins]. AB - The aim of the study is to construct two vectors for efficient expression of soluble recombinant proteins. The first vector was constructed by cloning the HisSUMO fragment into an expression vector pET30a(+) to fuse with the gene of interest (designated as HisSUMO Express). The second vector was constructed in the same way, but with a hydroxylamine cleavage site between HisSUMO and the gene of interest for an economic purpose (designated as HisSUMO Economic). The mouse fibroblast growth factor-21(mFGF-21), which was difficult to express in routine used expression vectors, was taken as an example to test the vectors. The results showed that the mFGF-21 was expressed at high level in both vectors. The Sumo/mFGF-21 fusion protein accounted for more than 40% of the total bacterial protein. The fusion protein was purified with Ni-TNA column, and the HisSUMO was removed by cleavage of the fusion protein with either hydroxylamine solution or SUMO protease I. The concentration of the purified mFGF-21 mature protein was 54 mg/L and the recovery rate was 6%. The purified proteins derived from either hydroxylamine or SUMO protease I cleavage could stimulate glucose up-take by adipocytes. These results indicated that both HisSUMO Express and HisSUMO Economic were useful expression vectors for efficient expression of soluble recombinant proteins. PMID- 20353101 TI - [Construction of pGL3-SM22-SCAP (D443N) eukaryotic expression vector and its expression in CHO cells]. AB - The experiment was designed to investigate the function of SREBP cleavage activating protein (SCAP) mutant (D443N) by constructing an eukaryotic expressive vector using a smooth muscle specific promoter SM22 (pGL3-SM22-SCAP(D443N)). SM22 promoter (pSM22) was amplified from genome DNA of mice by nested PCR, and then cloned into pMD-T vector. The SM22 promoter fragment released from the vector by Kpn I and Hind III digestion was sub-cloned into pGL3-control-Luc vector, to form pGL3-SM22-Luc. The activity of pSM22 in human vascular smooth muscle cells (VSMCs) was tested using Dual-Luciferase Reporter System. SCAP(D443) mutant amplified from plasmid pTK-HSV-SCAP(D443N) and pSM22 from mice liver were cloned into pGL3-control vector to construct pGL3-SM22-SCAP(D443N) which was transfected into Chinese hamster ovary cells (CHO) to test SCAP(D443) expression by real-time PCR and Western blot. The sequence and construction of pGL3-SM22-SCAP(D443N) were correct. SM22 promoter activity initiated the expression of luciferase in VSMCs and also drove SCAP(D443) expression in transfected CHO cells. The pGL3-SM22 SCAP(D443N) eukaryotic expression vector was successfully constructed and the recombinant vector provides a powerful approach in investigating the function and regulation of SCAP and also in producing vascular smooth muscle specific SCAP transgenic mice. PMID- 20353103 TI - [Cloning, expression, purification and activity assay of Trypanosoma brucei phenylalanyl-tRNA synthetase in Escherichia coli]. AB - Phenylalany--tRNA synthetase is a key enzyme for protein synthesis in Trypanosoma. Its validation as an inhibition. target will enable the development of a new generation of anti-Trypanosoma drugs. However, little is known about the isolation of the Trypanosoma Phenylalanyl-tRNA synthetase. Here we report the cloning, expression, purification, and activity assay of Phenylalanyl-tRNA synthetase from Trypanosoma brucei in Escherichia coli host. We co-cloned the alpha-subunit and beta-subunit of Phenylalanyl-tRNA synthetase from Trypanosoma brucei genomic DNA into the co-expression vector pCOLADuet. We successfully expressed the Trypanosoma brucei Phenylalanyl-tRNA synthetase in E. coli host, purified the whole enzyme by Ni-Hind affinity column and verified it by Western blotting. In addition, we tested its enzymatic activity by isotope labeling. The whole work laid a solid foundation for in vitro the screening and optimization of Trypanosoma brucei phenylalanyl-tRNA synthetase inhibitors. PMID- 20353104 TI - [On acupuncture-moxibustion research needing dependence on clinical practice]. AB - In this present paper, the current situation and the main features in acupuncture moxibustion clinic are analyzed. The preliminary conclusion is that acupuncture moxibustion research should proceed from the actual situation, take the treatment as the carrier, be scientifically designed and study in a deep-going way according to the methods of medical science for the acupuncture-moxibustion treatment with obvious clinical effect and specific action, then can get the scientific data and conclusion to illustrate the clinical problem and increase the therapeutic effect with important instruction significance for clinical practice. Clinical practice of acupuncture and moxibustion is the basis of all acupuncture-moxibustion research. PMID- 20353105 TI - [Comprehensive therapeutic protocol of electroacupuncture combined with Chinese herbs and rehabilitation training for treatment of cerebral infarction: a multi center randomized controlled trial]. AB - OBJECTIVE: To evaluate the therapeutic effect of comprehensive therapeutic protocol of electroacupuncture combined with active-blood-and-dissolve-stasis herbs and rehabilitation training for cerebral infarction. METHODS: A multi center randomized controlled trial was done, three hundred and twenty cases were divided into four groups: electroacupuncture combined with active-blood and dissolve-stasis herbs and rehabilitation training group (group A), electroacupuncture combined with rehabilitation training group (group B), herbs combined with rehabilitation training group (group C) and rehabilitation training group (group D), 80 cases in each group. The following two groups of acupoints were used alternatively in electroacupuncture treatment: the first group including Vasomotor Area, Jianyu (LI 15), Biguan (ST 31), Hegu (LI 4) and Taichong (LR 3); the second group including Motor Area, Quchi (LI 11), Yanglingquan (GB 34) and Shenshu (BL 23). 20 mL Xiangdan injection and 250 mL 5% glucose injection or 250 mL 0.9% sodium chloride injection were used by intravenous drip in herbs treatment once a day. The rehabilitation training was performed by the professional physical therapist. Each group was treated with corresponding treatment protocol. The therapeutic effect was evaluated by index of the mortality or disability rate 3 months after the onset of disease. The intention to treat analysis (ITT) was used in data. RESULTS: The mortality or handicap rate 3 months after the onset of disease of four groups were 17.5% (14/80) in group A, 22.5% (18/80) in group B, 40. 0% (32/80) in group C, and 31.3% (25/80) in group D, respectively. The group A has a best therapeutic effect (vs group C, group D, both P<0.05), and there was no adverse event. CONCLUSION: The combined application of electroacupuncture, active-blood and dissolve-stasis herbs and rehabilitation training is a better treatment for cerebral infarction in clinic. PMID- 20353106 TI - [Effect of acupuncture on the activity of the peripheral blood T lymphocyte subsets and NK cells in patients with colorectal cancer liver metastasis]. AB - OBJECTIVE: To study the effect of acupuncture on the immune function of patients with colorectal cancer liver metastasis. METHODS: Sixty cases with colorectal cancer liver metastasis confirmed by pathology and mageology diagnosis were treated with acupuncture. Zusanli (ST 36), Sanyinjiao (SP 6), Neiguan (PC 6), Shangjuxu (ST 37), Hegu (LI 4), Taixi (KI 3), Taichong (LR 3) ,Yinlingquan (SP 9), Yanglingquan (GB 34), etc. were selected for acupuncture, and Shenque (CV 8), Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36) were selected for moxibustion. The changes of CD(3) , CD(4) , CD(8) T cells and NK cells in value were examined with flow cytometry before and after treatment. RESULTS: The value of T lymphocyte subsets such as CD(3) , CD(4), and CD(8) , as well as NK cells were obviously increased after treatment, and there were significant differences between them before and after treatment. CONCLUSION: Acupuncture can improve the immune function of patients with colorectal cancer liver metastasis. PMID- 20353107 TI - [Clinical observation on therapeutic effect of electroacupuncture on chronic prostatitis and detection of urethral sphincter EMG]. AB - OBJECTIVE: To observe the clinical therapeutic effect of electroacupuncture for chronic prostatitis and investigate its mechanism. METHODS: Forty-eight cases were randomly divided into an electroacupuncture group and a western medicine group, 24 cases in each group. The electroacupuncture group was treated by electroacupuncture and Guanyuan (CV 4), Zhongji (CV 3). Ciliao (BL 32) and Huiyang (BL 35) were selected as main acupoints. The western medicine group was treated by oral administration of Sparfloxacin tablets and Prostat tablets. The scores of NIH-CPSI, changes in uroflow rate-urethral sphincter EMG and their therapeutic effects were observed. RESULTS: The total effective rate was 87.5 % in the electroacupuncture group which, was better than 62. 5% in the western medicine group (P(<0. 05). There were significant differences in the scores of NIH-CPSI and Q(max), Q(ave), TL value before and after treatment in the electroacupuncture group (all P<0.05), and with a significant difference in the scores of NIH-CPSI and Q(max). Q(ave), TL value after treatment between the two groups (all P<0.05). CONCLUSION: Electroacupuncture based on syndrome differentiation has better therapeutic effect on chronic prostatitis than that of routine clinical medicine. PMID- 20353108 TI - [Influence of acupuncture on isoprostane in patients with Alzheimer's disease]. AB - OBJECTIVE: To explore the clinical therapeutic effect of acupuncture on Alzheimer's disease (AD) and its mechanism. METHODS: Twenty patients with Alzheimer's disease were treated by acupuncture with reinforcing kidney and activating blood method for 12 weeks and Baihui (GV 20), Shenshu (BL 23), Xuehai (SP 10) and Geshu (BL 17) were selected. The clinical therapeutic effect were assessed by comparing the scores of Alzheimer's Disease Assessment Scale Cognitive Section (ADAS-Cog) and 8-IPF2alpha concentration in cerebrospinal fluid, blood and urine before and after treatment were detected by using enzyme linked immunosorbent assay. RESULTS: After treatment, the effective rate was 90.0%. The score of ADAS-Cog was 35. 70 +/- 14. 70 before treatment and 31. 45 +/ 4. 08 after treatment, with a significant difference (P<0. 001). The concentration of 8-IPF2alpha in cerebrospinal fluid, blood and urine were all significantly decreased after treatment (all P<0.001). CONCLUSION: Acupuncture can improve the cognitive ability of AD patients and its possible mechanism may be relative to the decrease in lipid peroxidation in AD patients' brain. PMID- 20353109 TI - [Clinical observation on treatment of acupuncture for different stages of Bell's palsy]. AB - OBJECTIVE: To observe the therapeutic effects of acupuncture for treatment of different stages of Bell's palsy, and explore the best intervention period. METHODS: Forty cases of Bell's palsy patients were divided into three groups according to their onset time: an active stage group, a resting stage group and a recovery stage group. The scores were evaluated with Sunnybrook Facial Nerve Evaluation System and Facial Disability Index Questionnaire (FDI). All three groups were treated with acupuncture. Fengchi (GB 20), Dicang (ST 4), Jiache (ST 6), Qianzheng (Extra), Sibai (ST 2), Yangbai (GB 14) on the affected side and Hegu (LI 4) on the healthy side were selected as main points. Dazhui (GV 14), Chengjiang (CV 24), Shuigou (GV 26) and Cuanzhu (BL 2), Yuyao (EX-HN 4), Yifeng (TE 17), Tinghui (GB 2), Quanliao (SI 18), Xiaguan (ST 7), Yingxiang (LI 20) on the affected side were selected as adjuvant points. Operation: reducing was performed at Fengchi (GB 20), Hegu (LI 4) and Dazhui (GV 14), while mild tonification and mild purgation was performed at other points. The therapeutic effect was evaluated again by scoring after the clinical recovery or treatment of 20 times. RESULTS: (1) Acupuncture was effective for the Bell's palsy in active stage, resting stage and recovery stage (all P<0. 01); (2) The obvious effective rate of acupuncture for treatment of Bell's palsy in the active stage group was obviously superior to those of resting stage group and recovery stage (both P<0. 01). (3) There was no significant difference of the obvious effective rate between the resting stage group and the recovery stage group (P>0. 05). CONCLUSION: Acupuncture has a good therapeutic effect for treatment of Bell's palsy, and the therapeutic effect is most obvious with intervention of treatment in the active stage. PMID- 20353110 TI - [Clinical observation on electroacupuncture combined with acupoint injection for treatment of early postoperative inflammatory intestinal obstruction]. AB - OBJECTIVE: To search for a better therapy for early postoperative inflammatory small bowel obstruction (EPISBO). METHODS: Two hundred and forty cases were divided into four groups according to admitting order, 60 cases in each group. Routine treatments in western medicine were used in group A including gastrointestinal decompression, parenteral nutrition, anti-infection, supportive therapy and so on. Group B was treated with electroacupuncture in Zusanli (ST 36), Shangjuxu (ST 37) etc. in addition to those given in group A. Group C was treated with acupoint injection with Neostigmine in Dachangshu (BL 25), Zusanli (ST 36) etc. in addition to the treatment used in group A. Group D was treated with all of the treatments used in group A, B and C. RESULTS: The total effective rate was 93. 3% in group A, 96. 7% in group B, 100.0% in group C and group D. There was no significant difference among the four groups (P>0. 05). The average recovery time of bowel sound was (11. 512. 9) days in group A, (9. 3 +/- 2.5) days in group B, (5.6 +/- 3.5) days in group C and (2. 2 +/- 1.7) days in group D. The average anal exsufflation time was (12. 5 +/- 3. 1) days in group A, (10. 7 +/- 3.6) days in group B, (7. 2 +/- 3. 1) days in group C and (2. 5 +/- 1. 5) days in group D. Group D was superior to those of other three groups obviously, and there were significant differences between them (all P<0. 01). CONCLUSION: Electroacupuncture combined with acupoint injection has a satisfied therapeutic effect for treatment of EPISBO. PMID- 20353111 TI - [Clinical observation on electroacupuncture combined with rehabilitation techniques for treatment of shoulder subluxation after stroke]. AB - OBJECTIVE: To compare the therapeutic effect difference between electroacupuncture combined with rehabilitation techniques and simple rehabilitation techniques for treatment of the shoulder subluxation after stroke. METHODS: Sixty cases of shoulder subluxation patients were divided into an acupuncture combined with rehabilitation group (30 cases) and a rehabilitation group (30 cases). The acupuncture combined with rehabilitation group was treated with electroacupuncture at Jianyu (LI 15), Jianliao (TE 14) and Jianzhen (SI 9) etc. combined with rehabilitation treatment, the rehabilitation group was treated with rehabilitation only. The therapeutic effects were evaluated and the pain score of the shoulder joint, passive range of motion of shoulder joint, the muscle strength of middle group of the deltoid and the function grade of the upper limbs motion of the two groups were evaluated before and after treatment. RESULTS: The acupuncture combined with rehabilitation group was superior to that of the rehabilitation group in pain score of the shoulder joint, passive range of motion of shoulder joint, the muscle strength of middle group of the deltoid and the function grade of the upper limbs motion with significant differences between the two groups (all P<0.05); the total effective rate of 93. 3% in the acupuncture combined with rehabilitation group was superior to that of 73.3% in the rehabilitation group (P<0.05). CONCLUSION: The therapy of electroacupuncture combined with rehabilitation techniques can act a good regulating role on muscle strength and the muscular tension of shoulder joint and the muscles around the scapula through many steps, and can effectively improve the shoulder subluxation. PMID- 20353112 TI - [Study on the effects of the auricular acupuncture with different manipulations for rapid analgesia on the patients with lumbar disc hernia]. AB - OBJECTIVE: To compare the effects of the point-to-point needling and perpendicular needling of auricular acupuncture for rapid analgesia on the patients with lumbar disc hernia, and find which method is better for this disease. METHODS: Ninety two patients were paired according to the three factors as sex, age and degree of pain, and then randomly divided into the point-to-point needling group and perpendicular needling group. The methods of point-to-point needling through the skin and perpendicular needling towardS the skin were respectively applied at bilateral lumbar areas as auricular acupuncture, and added acupoints following the change of symptom. All patients accorded with the demands of McGill pain questionnaire (MPQ), before treatment, 5 and 30 min after treatment, the accumulated score of pain was recorded respectively for observing the difference of the effects in both groups. RESULTS: After 5 min treatment, the effect of analgesia on the male patients in the point-to-point needling group was better than that of in the perpendicular needling group (P<0.05), but there was no difference on the female patients in both groups (P>0.05). After 30 min treatment, the effect of analgesia in the point-to-point needling group was better than that of the perpendicular needling group (P<0.05). Besides the patients with light degree pain, there was no significant difference between the two groups after 5 min treatment as score of pain (P>0.05), paired t-test showed that the effects of analgesia on the patients with lumbar disc hernia in the point-to-point needling group was better than that of perpendicular needling group (P<0.05). CONCLUSION: The point-to-point needling method can rapidly relieve patients' lumbar disc hernia of pain, which is better than the perpendicular needling method. PMID- 20353113 TI - [Investigation on the real herb of Mugwort leaf and the standard of its processing for moxibustion]. AB - Mugwort leaf is the traditional herb being used for moxibustion. Although its place of production and the course of making Mugwort floss have been described in detail, there is no unified standard about the quality and processing of Mugwort floss until now, which seriously affect on the popularity and application of moxibustion. In accordance with the real herb of Mugwort leaf and floss as well as its processing and quality judgment, this paper thoroughly analyze the related data including ancient documents, modern research results and clinical applications. The authors consider that the Mugwort floss in the market is lack of regulations for its processing, and it needs to be discussed the way to judge the quality of Mugwort leaf by volatile oil, suggesting that the further study on the quality control of Mugwort leaf and floss has to be carried out from multiple aspects, such as physical attributes and chemical characteristics. PMID- 20353114 TI - [Effects of electroacupuncture of different frequencies for treatment of patients with refractory tennis elbow syndrome]. AB - OBJECTIVE: To observe the different effects of electroacupuncture of different frequencies for treatment of patients with refractory tennis elbow syndrome. METHODS: Eighty five patients with refractory tennis elbow syndrome were randomly devided into continuous wave group (n=41) and rarefaction wave group (n= 44). The same acupoints were selected in both groups, and the major acupoints were the tenderness point around affected area in both groups. The Visual Analogue Scale (VAS) was used to evaluate the tenderness score of each patient in both groups. The effectiveness was evaluated by the tenderness score. RESULTS: The effective rate was 82. 9% in continuous wave group, and 84. 1% in rarefaction wave group, with no significant difference in statistical analysis (P>0.05). The healing rate was 56. 8% in rarefaction wave group, better than 31. 7% in continuous wave group (P<0.05). The VAS scores were significantly reduced after electroacupuncture treatment in both groups (both P<0.001). There was significant difference in decreasing the VAS score between two groups after treatment (P<0.05), and the rarefaction wave group was better than the continuous wave group. CONCLUSION: The electroacupuncture of rarefaction wave is better than the electroacupuncture of continuous wave, therefore, it is a better treatment for refractory tennis elbow syndrome. PMID- 20353115 TI - [Study on the effect of cluster needling of scalp acupuncture on the plasticity protein MAP-2 in rats with focal cerebral infarction]. AB - OBJECTIVE: To investigate the material base and underlying mechanism of the effect of cluster needling of scalp acupuncture on the neuronal plasticity in rats with focal cerebral infarction. METHODS: The model rats with acute cerebral infarction were made by blocking the middle cerebral artery with monofilament. One hundred and thirty two Wistar rats were randomly divided into 4 groups: sham operation group (A), model group (B), point-to-point scalp acupuncture group (C) and cluster-needling of scalp acupunture group (D). Puncturing from "Baihui (GV 20)" to "Qubin (GB 7)" was used in group C. Cluster needling of scalp acupuncture was used in group D, in which needles were inserted forward and slantingly into "Baihui (GV 20)" and its left and right sides at 4 mm. In both groups, the treatment was carried out with rapid twirling reinforcing-reducing for 1 min then retaining needle for 30 min, once a day, 6 days in one course, for treating 4 courses. There was no treatment for group A and B. The change of neurological function was evaluated with Bederson score, while the expression of microtubule associated protein 2 (MAP-2) in the ischemic penumbra was examined with immunohistochemistry (streptavidin-peroxidase method). RESULTS: In comparison,with group B, the score of neurological function in group D decreased on 7th day (P<0.05), while the scors in group C and D also decreased on 14th and 28th days (both P<0.05). As compared with group C, the score of neurological function in group D obviously decreased on 28th days (P<0. 05). Comparing with group B, the expression of MAP-2 on the ischemic cortex was significantly increased in group D and C on 7th, 14th and 28th days (all P<0. 05), however, this expression in group D was higher than that in group C on 14th and 28th days (P<0. 05). CONCLUSION: Cluster needling of scalp acupuncture can improve the neurological function of rats with focal cerebral infarction, and increase the expression of MAP-2 in the ischemic penumbra. PMID- 20353116 TI - [Study on the manifestation of facial infrared thermography induced by acupuncturing Guangming (GB 37) and Hegu (LI 4)]. AB - OBJECTIVE: To manifest the specificity of acupoints objectively through observing the relationship of both Guangming (GB 37) and Hegu (LI 4) with the some areas of face. METHODS: The patients with peripheral facial paralysis were divided into the Guangming (GB 37) group and Hegu (LI 4) group, and punctured respectively. Before and after treatment, the distribution and change of facial temperatures were measured with infrared thermography and the data on each area was comparatively analyzed. RESULTS: After punctured at Guangming (GB 37), the temperature went up in the areas around the eyes of both health and affected sides, especially on the affected side, which was significantly different from the other facial areas (all P<0.05). After punctured at Hegu (IA 4), the temperature obviously went up in the area around the mouth, which was significantly different from other areas of face, such as the areas of Yintag and health eye. The temperature in the area around the affected eye was significantly higher than that of the area around the health eye. CONCLUSION: There is some close coordination between Guangming (GB 37) and eye area, as well as between Hegu (LI 4) and mouth area, suggesting the specificity of acupoints. PMID- 20353117 TI - [Randomized controlled trial on effect of Tuina for treatment of sub-health people of somatic pain]. AB - OBJECTIVE: To evaluate the clinical effect and safety of Tuina for treatment of somatic pain of sub-health. METHODS: A randomized, double-blind and blank parallel controlled trial was done. The experiment group was treated with Tuina and the control group lied down for rest, 45 minutes each time, twice each week for three weeks. RESULTS: Tuina treatment could improve more on sensory, affective, evaluation, pain rating index and extant pain intensity of the pain index, and score of subjective sensation of life quality and health status together with physiology and psychology field of life quality. CONCLUSION: Massage is an effective therapy for treatment of somatic pain of sub-health without adverse reactions and it should be generalized to application. PMID- 20353118 TI - [Great master of TCM CHENG Xin-nong 's three key points of acupuncture clinical experience]. AB - Professor CHENG Xin-nong has practiced in medicine for over 70 years and gained profound clinical experience. He points out that these rules below should be obeyed to improve the efficacy of acupuncture. Firstly, the diseases should be diagnosed basing on meridians order and meridian syndrome differentiation while acupoints should be chosen and adjuncted according to their main medical functions. Secondly, the three Cai inserting method should be flexibly applied on different patients, by adjusting the needling depth and manipulation to reinforce the deficiency and reduce the excess. Thirdly, the arrival of qi is a key point and such methods as the retaining of needles, electroacupuncture and moxibustion should be cointegrated used. PMID- 20353119 TI - [Thinking on methodologies and problems existed in clinical study of acupuncture and moxibustion]. AB - The modernization and internationalization of acupuncture and moxibustion is inevitable trends to develop acupuncture and moxibustion. However, the acupuncture research findings in China are not accepted by the mainstream medicine abroad. The major problems are that the study purposes are not specific and the modern scientific research methods are not rationally used in acupuncture clinical study. Two major issues in acupuncture clinical study in China are the evaluation of the specificity of acupuncture and the overall effect of acupuncture treatment. The core and basis of acupuncture clinical study are the clarity of study purpose, following the law of evidence-based medicine and rational selection of modern scientific methods. On the basis of the characteristics of acupuncture and the specialty of acupuncture clinical study, for instance, the types of trial design, blind methods, the selection of control group and outcome assessment system, the objective of this paper provides research strategies for researchers and to improve the overall level of research in the acupuncture clinical study. PMID- 20353120 TI - [Preventive effect of acupoint injection at neiguan (PC 6) on postoperative nausea and vomiting after laparoscopic gynecologic surgery]. AB - OBJECTIVE: To investigate the method for preventing the postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery. METHODS: One hundred and twenty patients being for laparoscopic gynecologic surgery at I- II grade as American Society of anesthesiologists (ASA) were randomly divided into three groups, 40 cases in each group. Twenty minutes before the operation, the mixture of 2. 5 mg Droperidol (1 mL) and 1 mL 0. 9% sodium chloride solution was injected into the bilateral Neiguan (PC 6) in group I , and an intravenous injection with 1 mL Droperidol was used in group II , while there was no treatment carried out in group Ill'. Twenty four hours after the operation, the frequency and degree of nausea and vomiting were observed and scored according to the criteria standard. RESULTS: The incidence rate of nausea was 10. 0% (4/40) in group I , 57. 5% (23/40) in group II , which was significantly different from 80. 0% (32/40) in group III (P<0. 01, P<0. 05, respectively), while it was lower in group I than in group II (P<0. 01). The incidence rate of vomiting was 7. 5% (3/40) in group I , 52. 5% (21/40) in group II , which was significantly different from 75.0% (30/40) in group III (P<0.01, P<0.05 respectively), while it was lower in group I than in group II (P<0.01). No complication, such as obvious drowsiness, anxiety and extracorticospinal tract reaction, was observed among the three groups. CONCLUSION: Acupoint injection at Neiguan (PC 6) with a small dose of Droperidol can effectively prevent the PONV after laparoscopic gynecologic surgery without other adverse effects. PMID- 20353121 TI - [Thinking on teaching experiences of acupuncture manipulation and moxibustion method in western medicine college]. AB - For the problems existed in the teaching of acupuncture manipulation and moxibustion method in western medicine college, for instance, the lack of credit hours and divorce from theory and practice, in addition to visualization teaching, this paper introduced case study and problem-centered teaching approaches. Besides clinical teaching, this paper emphasized anatomical knowledge which strengthen memory. In this way, the quality of teaching and teaching effects will be improved in the education of acupuncture manipulation and moxibustion method in western medicine college. PMID- 20353122 TI - [Brief summary on ancient moxibustion for treatment of fabei]. AB - To formulate the theory and experiences of physicians of successive dynasties on moxibustion for treatment of fabei, the medical cases and theory of ancient physicians are analyzed. It is found that moxibustion treatment has unique efficiency on fabei, which can come back to life, advert a danger, be easy to implement with low cost and be well worth studying futher and promoting the application. The concrete manipulation of the moxibustion treatment are garlic separated moxibustion, direct moxibustion, mori moxibustion and so on. PMID- 20353123 TI - [Advances in studies on the correlation between acupuncture-moxibustion treatment and mast cells]. AB - The present paper reviewed the literatures at home and abroad in the recent ten years; it stated the effects of acupuncture on local mast cells around meridian acupoints and affected area; it stated the advanced development in the possible mechanism of the efficacy of acupuncture treatment for diseases related to mast cells in recent ten years. Currently, the underlying mechanism of the efficacy of acupuncture on mast cells still remains mysterious. It needs further investigations to study the effect of mast cells in acupuncture treatment and the mechanism of the effects of moxibustion on mast cells. PMID- 20353124 TI - Post Caesarean section infective morbidity in HIV-positive women at a tertiary training hospital in Zimbabwe. AB - OBJECTIVE: To investigate the infective morbidity in HIV-positive and HIV negative women whose babies were delivered by Caesarean section. DESIGN: A hospital based, prospective study: part of a larger operational research project. SETTING: Harare Maternity Hospital, a tertiary referral teaching hospital in Harare, Zimbabwe. SUBJECT: 164 HIV-positive and 382 HIV-negative women who were delivered of their babies by Caesarean sections. MAIN OUTCOME MEASURES: Minor and major infective complications. RESULTS: The results compare HIV-positive and HIV negative women, 18/164 (10.9%) HIV-positive women developed anaemia requiring blood transfusion compared with 15/382 (3.9%) HIV-negative women. The difference was statistically significant (RR 3.05). HIV-positive women had a statistically significant increase in the incidence of post operative fever (RR 1.3) and wound sepsis/sinus (p = 0.002). CONCLUSION: Our study indicates that HIV-positive women who were given prophylactic pre-operative antibiotics were at an increased risk of minor infective complications and blood transfusion post Caesarean section. The risk of blood transfusion was higher in women who had a pre-operative haemoglobin of 10.5 grams/dl. Post operative fever, wound sepsis and wound sinus was commoner in HIV-positive when compared to HIV-negative women. PMID- 20353125 TI - Seroprevalence of Toxoplasma gondii in Nazareth Town, Ethiopia. AB - OBJECTIVE: To determine seroprevalence of toxoplasmosis, assess its zoonotic importance and identify factors associated with seroprevalence. DESIGN: Questionnaire survey and serological studies. SUBJECTS: Questionnaire survey and 65 serum samples from male and female urban and peri-urban residents aged between 15 days and 65 years. MAIN OUTCOME MEASURES: Feeding habits, purpose of keeping cats and association with family members, serologic evidence of toxoplasmosis by the Modified Direct Agglutination Test (MDAT), examination of HIV status using the HIV-Spot Test. RESULTS: Over 86% of the interviewed people had a history of consumption of raw or undercooked mutton and had close contact with cats. Of the serum samples analyzed by the MDAT 60% had serologic evidence of Toxoplasma infection. Significantly higher MDAT tiers were encountered both in pregnant and immunocompromised individuals. The risk factors associated with Toxoplasma infection, i.e. raw or undercooked mutton consumption and presence of cats appeared significant. CONCLUSION AND RECOMMENDATIONS: The significance of toxoplasmosis as a disease of zoonotic importance was demonstrated. Close contact between family members and the consumption of raw or undercooked mutton were the major risk factors in the transmission of the disease. Considering the relatively high prevalence as revealed by this study it would be important to conduct studies on a wider scale. It would also be important to increase public awareness and upgrade the knowledge on congenital toxoplasmosis. PMID- 20353126 TI - Therapeutic feeding at a rural hospital in Zimbabwe. AB - OBJECTIVE: The purpose of this audit was to review treatment outcomes of participants in the Cooperazione e sviluppo/Cooperation and Development (CESVI), Therapeutic Feeding Programme (TFP) (i.e., death vs cure vs absconded) and to make recommendations for improving this and other similar programmes. DESIGN: This study was a retrospective chart review. The charts of all patients admitted to the TFP from 1 January 2005 to 31 December 2005 were analyzed. SETTING: The Salvation Army Howard Hospital is a district hospital in rural Zimbabwe. The hospital provides both inpatient and outpatient paediatric care. SUBJECTS: 132 consecutive children were enrolled in the TFP in 2005. INTERVENTION: The objectives of the TFP included identification of children with severe malnutrition; treating complications associated with severe malnutrition and prescribing appropriate dietary treatment. MAIN OUTCOME MEASURES: The main outcome of interest was whether TFP participants died, were cured, or absconded. We assessed factors that may be associated with these outcomes such as age, gender, comorbidities and length of stay. RESULTS: Female children and children with marasmus were more likely to abscond from the programme than male children and children with kwashiorkor (p = 0.041, 0.039 respectively). The majority of children who died while in the programme did so within the first week of their admission. The majority of children who were cured while in the programme achieved this goal after two weeks of hospitalization (p < 0.0001). CONCLUSION: Given the contextual factors in rural African settings that could potentially impede the healthy growth and development of children, this review has produced programmatic recommendations and suggestions for future research directions. PMID- 20353127 TI - Schizophrenia: management and family burden. AB - OBJECTIVE: To explore schizophrenia with respect to its management, causes, risk factors as well as the impact it has in families regarding the burden and social networks support. METHODS: Desk literature reviews. RESULTS: The findings are that patients with schizophrenia typically have great difficulty following a medication regimen, but they also have the greatest potential for benefiting from adherence. As with other chronic diseases that lack a definitive cure, the individual's service/recovery plan must include treatment interventions directed towards decreasing manifestations of the illness, rehabilitative services, enhancing adaptive skills, and social support mobilization aimed at optimizing function and quality of life. CONCLUSION: Finally, this paper is not exhaustive, but a pointer for further readings. PMID- 20353128 TI - The prevalence of diabetic nephropathy in adult patients with insulin dependent diabetes mellitus attending Parirenyatwa Diabetic Clinic, Harare. AB - OBJECTIVE: The objective of this study was to determine the prevalence of diabetic nephropathy in a diabetic clinic in a tertiary hospital setting in Zimbabwe. DESIGN: Descriptive cross sectional study. SETTING: Diabetic clinic in a tertiary hospital. SUBJECTS: 75 insulin dependent diabetic consenting adults aged over 18 years. METHODS: Consecutive sampling of 75 insulin dependent consenting subjects presenting at the Parirenyatwa Diabetic Clinic was conducted over a four month period. Patients were tested for proteinuria using dipsticks and were divided into dipstick positive and dipstick negative. The dipstick positive samples were sent to the laboratory for protein quantification. The dipstick negative samples were tested for microalbuminuria. Urine albumin creatinine ratios were utilised to quantify the proteinuria. MAIN OUTCOME MEASURES: Prevalence of overt proteinuria and the prevalence of microalbuminuria. RESULTS: Overt proteinuria was found in 16 (21%) patients. Microalbuminuria was found in 9 (12%) of the patients. Nephropathy was, therefore, found in 25 (33%). CONCLUSION: There is a high prevalence of diabetic nephropathy in adult patients with insulin dependent diabetis mellitus attending Parirenyatwa Diabetic Clinic. PMID- 20353129 TI - Schistosomiasis infection among school children in the Zhaugwe resettlement area, Zimbabwe April 2005. AB - OBJECTIVES: To investigate the prevalence and factors associated with contracting schistosomiasis in Zhaugwe resettlement area of Shurugwi district. DESIGN: Cross sectional study. STUDY SETTING: The community in the Zhaugwe resettlement area of Shurugwi district, Midlands Province, Zimbabwe. SUBJECTS: School children in primary and secondary levels. MAIN OUTCOME MEASURES: Prevalence of schistosomiasis infection, risk factors for contracting schistosomiasis. RESULTS: Prevalence of S. haematobium and S. mansoni was 68% and 0.2%, respectively. Participating in watering the respondents' household garden (O.R = 8.1, 95% CI 1.65 to 40.2), fetching water for the home garden (O.R=3,96 95% CI 1.38 to 11.32), fishing with their legs in the water (O.R = 3.1 95% CI 1.6 to 5.8), bathing in the river or stream (O.R = 3.1 95% CI 1.68 to 5.8) were found to be statistically significantly associated with contracting schistosomiasis infection. Fishing with legs immersed in water, having a garden at home, and swimming in the river were positively associated with infection. Those who reported blood in their urine were 16 times more like to be positive for S. haematobium than those without. Vector snails were present at all water contact sites. CONCLUSION: Schistosomiasis is a major public health problem in the area. We recommend mass treatment of all school children in all other schools in the area. The community should be encouraged to cultivate Phytoloca dedocandra for snail control. PMID- 20353130 TI - Lipid profiles of apparently healthy adolescents in Calabar, Nigeria. AB - OBJECTIVE: To determine the lipid profiles of adolescents in Calabar, Nigeria. DESIGN: A cross sectional prospective study. SETTING: The study was carried out in Calabar, a city located on the south-eastern axis of Nigeria. Calabar is rapidly acquiring the status of a tourism destination in the country and as such the lifestyles of the city dwellers are changing rapidly. SUBJECTS: The subjects were apparently healthy students 10 to 18 years old attending day secondary schools in the city. A structured questionnaire was used to collect demographic and anthropometric data from the students. Blood samples were collected from 375 adolescents and used for analyzing their lipid profiles. MAIN OUTCOME MEASURES: Abnormal levels of serum lipids. RESULTS: The results showed that only one subject (0.3%) had an abnormally high total cholesterol (TC) level and 33% of the subjects had low levels of high density lipoprotein cholesterol (HDL-C). Borderline high levels of total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were found in 2.4%, 3.2% and 5.1% of subjects respectively. CONCLUSION: This study shows that the lipid profiles of Nigerians are low but gradually rising towards values seen in places where coronary heart disease occurs in epidemic proportions. This may point to an increased risk ofarteriosclerosis in future generations. PMID- 20353131 TI - Successful treatment of active haemorrhage from a duodenal diverticulum using surgicel (absorbable haemostat): a case report. AB - Haemorrhage is one of the rare but serious complications of duodenal diverticula. Current methods of treatment include: endoscopy with injection therapy or hemoclip application and diverticulectomy. In this paper we present the case of a 61 year old man with life threatening haemorrhage who was managed successfully with gentle packing of a bleeding duodenal diverticulum using SURGICEL (Absorbable Haemostat). This appears to be a simple and effective way of dealing with the problem especially in situations where other methods are ineffective or inapplicable. Early surgical intervention before the development of any coagulopathy increases the chances of a successful outcome. It has not been possible to find a similar report from a thorough literature search. PMID- 20353132 TI - Antimicrobial resistence of Shigella species isolated during 2004 and 2005 from selected sites in Zimbabwe. AB - OBJECTIVE: To determine the predominant serotype and antibiotic sensitivity pattern of Shigella isolates during 2004 and 2005 in Zimbabwe. DESIGN: Cross sectional study. SETTING: National Microbiology Reference Laboratory (NMRL), Harare, Zimbabwe. SAMPLE: 259 clinical isolates of Shigella species isolated during 2004 and 2005 in Zimbabwe were studied. These samples had been referred to the NMRL for further testing. MAIN OUTCOME MEASURES: Serotype and antibiotic sensitivity pattern of Shigella species. RESULTS: Of the 259 clinical isolates of Shigella tested the following species were serotyped; 141 (54.4%) were S. flexneri; 70 (27%) S. sonnei; 38 (14.7%) S. dysenteriae and 10 (3.9%) S. boydii. About 4% of all Shigella isolates tested showed full sensitivity to commonly used antibiotics, 20.8% were resistant to one antibiotic only while 75.3% were resistant to at least two antibiotics. The most common resistance among Shigella species was to cotrimoxazole (89%), tetracycline (73%), ampicillin (49%) and chloramphenicol (41%). High susceptibility among Shigella species was observed to nalidixic acid (86%), ciprofloxacin (99%) and ceftazidine (99%). CONCLUSION: There was a low drug resistance of Shigella species to nalidixic acid, a drug of choice in Zimbabwe, except among Shigella dysenteriae type 1 strains. Continuous monitoring of the susceptibility patterns of Shigella species is important in order to detect the emergence of drug resistance and to update guidelines for antibiotic treatment in shigellosis. PMID- 20353133 TI - Risk assessment at the primary health care level in Moshi, Tanzania: limits in predicting sexually transmitted infections among women. AB - OBJECTIVE: To identify risk factors for sexually transmitted infections (STI) and to evaluate the accuracy of using risk assessment for identifying infected women in Moshi, Tanzania. DESIGN: A cross sectional study. SETTING: Three primary health care clinics in Moshi. SUBJECTS: 382 consenting women attending the clinics for routine reproductive health care were interviewed followed by a pelvic examination between September and December 1999. Blood and genital specimens were collected for STI diagnosis. MAIN OUTCOME MEASURES: Prevalent STIs, risk factors and accuracy of using risk factors to identify infected women. RESULTS: Among 382 women, 118 (31%) had at least one STI diagnosed clinically or by a laboratory test; (T. vaginalis 21%, syphilis 4.2%, chlamydia and/or gonococcal cervicitis 3.2%, genital ulcer 4.5% and warts 2%). The risk of CT/GC cervicitis was greater among women aged < 20 years (p = 0.04), with cervical friability (p = 0.01) and with > 10 cervical leucocytes (p < 0.001), while having more than one partner in the past three months (p = 0.008) predicted syphilis infection. Trichomoniasis was associated with the presence of vaginal discharge (p = 0.001) and pH > 4.5 (p < 0.001). However, using these risk factors as a screening tool for various STIs achieved a low sensitivity and a low positive predictive value, hence a low utility for case detection. CONCLUSION: STIs were prevalent in this setting. However, risk factors were not a good tool for identifying infected women. While there is an urgent need to develop low cost microbiological tests for case detection, efforts should be made to maximise the available control strategies, such as proper treatment of symptomatic patients and their partners. PMID- 20353134 TI - Changes in the humoral immune responses after chemotherapy in single and co infected individuals with Schisosoma haematobium and Plasmodium falciparum. AB - OBJECTIVE: To determine the effects of chemotherapy on the humoral immune responses in single and coinfected individuals with Schistosoma haematobium and Plasmodium falciparum. DESIGN: Prospective assessment of the humoral immune responses after treatment with praziquantel for schistosomiasis and chloroquine for malaria. SETTING: The study was carried out in four rural schools in Goromonzi and Mtoko districts 50km and 143km away from Harare respectively where both schistosomiasis and malaria are endemic. SUBJECTS: 555 school children aged 8 to 19 years; 298 from Goromonzi and 257 from Mtoko. MAIN OUTCOME MEASURES: Standard ELISA assays were carried out on the sera for immmunoglobin A (IgA), immmunoglobin E (IgE), immmunoglobin M (IgM) and immmunoglobin G (IgG) against the Schistosoma haematobium soluble worm antigen (SWA), soluble egg antigen (SEA), cercaria antigen (CERCA) and the Plasmodium falciparum malaria antigen (MALA). Eosinophil count was also done on Giemsa stained smears. RESULTS: Treatment resulted in a decrease of sera IgA levels against SEA in those individuals that had schistosomiasis only and there was a significant increase of sera IgE against the cercaria antigen (p < 0.05). Those that had malaria whether singly or coinfected sera IgE against MALA decreased but sera IgE against SEA increased. Sera IgE against SEA increased significantly (p < 0.05) in those that had neither infections who had been given praziquantel treatment. Eosinophilia was evident in parasitic infections. CONCLUSION: Schistosomiasis is a problem in rural settings as in all the four schools > 50% of the pupils were infected, whilst those that were < 15 years of age had high egg intensities. There was a rise in sera IgE antibodies against SEA and CERCA in all the cases that were treated with praziquantel, an indication that treatment does alter the immune response favouring resistance to infection by Schistosoma haematobium. Those that had malaria singly or coinfected produced high levels of sera IgE against SEA an indication that malaria infection influences the cytokine environment to favour production of IgE isotypes against the schistosome egg antigen. PMID- 20353135 TI - Best practices for post natal care in Zimbabwe. AB - The purpose of post natal care for the mother is to avert or alleviate significant mortality and morbidity. During the immediate post partum period, the emphasis will be on monitoring to detect complications and assisting the mother to initiate care of the newborn, especially breastfeeding. In the latter post partum period, the aim is to confirm involution and healing of the genital tract, confirm continued good newborn care by the mother and offer protection against pregnancy to the couple. PMID- 20353138 TI - Effect of beta blockers on patient's lipid profiles. PMID- 20353139 TI - Are bisphosphonates effective in preventing fractures? PMID- 20353141 TI - Latent autoimmune diabetes in adults. PMID- 20353142 TI - Blood pressure treatment targets for uncomplicated hypertension. PMID- 20353143 TI - Effectiveness of B-complex vitamins for prevention of cardiovascular events. PMID- 20353144 TI - Diabetes mellitus: diagnosis and screening. AB - Based on etiology, diabetes is classified as type 1 diabetes mellitus, type 2 diabetes mellitus, latent autoimmune diabetes, maturity-onset diabetes of youth, and miscellaneous causes. The diagnosis is based on measurement of A1C level, fasting or random blood glucose level, or oral glucose tolerance testing. Although there are conflicting guidelines, most agree that patients with hypertension or hyperlipidemia should be screened for diabetes. Diabetes risk calculators have a high negative predictive value and help define patients who are unlikely to have diabetes. Tests that may help establish the type of diabetes or the continued need for insulin include those reflective of beta cell function, such as C peptide levels, and markers of immune-mediated beta cell destruction (e.g., autoantibodies to islet cells, insulin, glutamic acid decarboxylase, tyrosine phosphatase [IA-2a and IA-2beta]). Antibody testing is limited by availability, cost, and predictive value. PMID- 20353145 TI - Diagnosis and treatment of urethritis in men. AB - Symptoms of urethritis in men typically include urethral discharge, penile itching or tingling, and dysuria. A diagnosis can be made if at least one of the following is present: discharge, a positive result on a leukocyte esterase test in first-void urine, or at least 10 white blood cells per high-power field in urine sediment. The primary pathogens associated with urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae. Racial disparities in the prevalence of sexually transmitted infections persist in the United States, with rates of gonorrhea 40 times higher in black adolescent males than in white adolescent males. Recent studies have focused on identifying causes of nongonococcal urethritis and developing testing for atypical organisms, such as Mycoplasma genitalium and Ureaplasma species. Less common pathogens identified in patients with urethritis include Trichomonas species, adenovirus, and herpes simplex virus. History and examination findings can help distinguish urethritis from other urogenital syndromes, such as epididymitis, orchitis, and prostatitis. The goals of treatment include alleviating symptoms; preventing complications in the patient and his sexual partners; reducing the transmission of coinfections (particularly human immunodeficiency virus); identifying and treating the patient's contacts; and encouraging behavioral changes that will reduce the risk of recurrence. The combination of azithromycin or doxycycline plus ceftriaxone or cefixime is considered first-line empiric therapy in patients with urethritis. Expedited partner treatment, which involves giving patients prescriptions for partners who have not been examined by the physician, is advocated by the Centers for Disease Control and Prevention and has been approved in many states. There is an association between urethritis and an increased human immunodeficiency virus concentration in semen. PMID- 20353146 TI - Peripheral neuropathy: differential diagnosis and management. AB - Peripheral neuropathy has a variety of systemic, metabolic, and toxic causes. The most common treatable causes include diabetes mellitus, hypothyroidism, and nutritional deficiencies. The diagnosis requires careful clinical assessment, judicious laboratory testing, and electrodiagnostic studies or nerve biopsy if the diagnosis remains unclear. A systematic approach begins with localization of the lesion to the peripheral nerves, identification of the underlying etiology, and exclusion of potentially treatable causes. Initial blood tests should include a complete blood count, comprehensive metabolic profile, and measurement of erythrocyte sedimentation rate and fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; specialized tests should be ordered if clinically indicated. Lumbar puncture and cerebrospinal fluid analysis may be helpful in the diagnosis of Guillain-Barre syndrome and chronic inflammatory demyelinating neuropathy. Electrodiagnostic studies, including nerve conduction studies and electromyography, can help in the differentiation of axonal versus demyelinating or mixed neuropathy. Treatment should address the underlying disease process, correct any nutritional deficiencies, and provide symptomatic treatment. PMID- 20353147 TI - Skin and soft tissue infections in immunocompetent patients. AB - The increasing incidence of skin and soft tissue infections requires family physicians to be familiar with the management of these conditions. Evidence of systemic infection, such as fever, tachycardia, and hypotension, is an indication for inpatient management. Urgent surgical referral is imperative for those with life-threatening or rapidly advancing infections. In patients with uncomplicated abscesses measuring less than 5 cm in diameter, surgical drainage alone is the primary therapeutic intervention. Wound irrigation using tap water has similar outcomes as irrigation using sterile water. When antimicrobials are indicated, choice of agents depends on local resistance and susceptibility patterns. In settings where suspicion of methicillin-resistant Staphylococcus aureus (MRSA) is low, beta-lactam antibiotics are the first-line treatments for uncomplicated skin and soft tissue infections without focal coalescence or trauma. When empiric coverage for MRSA is indicated and the infection is uncomplicated, oral agents, such as tetracyclines, trimethoprim/sulfamethoxazole, and clindamycin, are preferred. Vancomycin is the first-line agent for MRSA in hospitalized patients, and newer agents, such as linezolid, daptomycin, and tigecycline, should be reserved for patients who do not respond to or cannot tolerate vancomycin therapy. There are insufficient data to support eradicating the carrier state in patients with MRSA or their contacts with nasal mupirocin or antibacterial body washes. Standard infection-control precautions, including proper and frequent handwashing, are a mainstay of MRSA prevention. PMID- 20353148 TI - Chronic productive cough. PMID- 20353150 TI - Stepwise phase transition in the formation of lithium amidoborane. AB - A stepwise phase transition in the formation of lithium amidoborane via the solid state reaction of lithium hydride and ammonia borane has been identified and investigated. Structural analyses reveal that a lithium amidoborane-ammonia borane complex (LiNH(2)BH(3).NH(3)BH(3)) and two allotropes of lithium amidoborane (denoted as alpha- and beta-LiNH(2)BH(3), both of which adopt orthorhombic symmetry) were formed in the process of synthesis. LiNH(2)BH(3).NH(3)BH(3) is the intermediate of the synthesis and adopts a monoclinic structure that features layered LiNH(2)BH(3) and NH(3)BH(3) molecules and contains both ionic and dihydrogen bonds. Unlike alpha-LiNH(2)BH(3), the units of the beta phase have two distinct Li(+) and [NH(2)BH(3)](-) environments. beta-LiNH(2)BH(3) can only be observed in energetic ball milling and transforms to alpha-LiNH(2)BH(3) upon extended milling. Both allotropes of LiNH(2)BH(3) exhibit similar thermal decomposition behavior, with 10.8 wt % H(2) released when heated to 180 degrees C; in contrast, LiNH(2)BH(3).NH(3)BH(3) releases approximately 14.3 wt % H(2) under the same conditions. PMID- 20353151 TI - Resistant starch, fermented resistant starch, and short-chain fatty acids reduce intestinal fat deposition in Caenorhabditis elegans. AB - Obesity is a growing global public health dilemma. The objective of this project is to develop and validate a screening mechanism for bioactive compounds that may reduce body fat and promote health. Resistant starch (RS) reduces body fat in rodents. Amylose starch that has a high content of RS, endogenous compounds obtained from the ceca of amylose starch fed mice (fermented RS), and individual short-chain fatty acids (SCFA) were tested. The Caenorhabditis elegans model and Nile red staining were selected to determine the intestinal fat deposition response to bioactive components. The fluorescence intensity of Nile red was reduced to 76.5% (amylose starch), 78.8% (fermented RS), 63.6% (butyrate), or 28 80% (SCFAs) of controls, respectively (P < 0.001). The reduced intestinal fat deposition suggests reduced food intake or increased energy expenditure. C. elegans is a practical animal model to screen for bioactive compounds that may prevent or treat obesity. PMID- 20353152 TI - A series of alpha-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase IIalpha catalytic activity. AB - A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel of human tumor cells and suppressed tumor growth in mice. The mechanism research revealed that TSC24 was not only an iron chelator but also a topoisomerase IIalpha catalytic inhibitor. Its inhibition on topoisomerase IIalpha was due to direct interaction with the ATPase domain of topoisomerase IIalpha which led to the block of ATP hydrolysis. Molecular docking predicted that TSC24 might bind at the ATP binding site, which was confirmed by the competitive inhibition assay. These results about the mechanisms involved in the anticancer activities of thiosemicarbazones will aid in the rational design of novel topoisomerase II-targeted drugs and will provide insights into the discovery and development of novel cancer therapeutics based on the dual activity to chelate iron and to inhibit the catalytic activity of topoisomerase IIalpha. PMID- 20353153 TI - Immobilization of peptides with distinct biological activities onto stem cell culture substrates using orthogonal chemistries. AB - We have used the orthogonal carbodiimide condensation and copper-catalyzed azide alkyne "click" cycloaddition (CuAAC) reactions to prepare self-assembled monolayers that present distinct peptides to stem cells in a bioinert background. The approach involved first forming mixed SAMs with three components: (i) an azide-terminated hexaethylene glycol alkanethiolate (HS-EG6-N3), (ii) a carboxylate-terminated hexaethylene glycol alkanethiolate (HS-EG6-COOH), and (iii) a triethylene glycol alkanethiolate (HS-EG3). An acetylene-bearing peptide and an amine-terminated peptide were then immobilized to these substrates using a "click" CuAAC reaction and a carbodiimide condensation reaction, respectively. Polarization-modulated infrared reflectance-absorbance spectroscopic analysis demonstrated formation of well-ordered, close-packed self-assembled monolayers (SAMs), chemoselective conjugation of amine-terminated peptides to surface carboxylate groups, and subsequent conjugation of acetylene-terminated peptides to the azide groups on SAMs. Varying the mole fraction of HS-EG6-N3, HS-EG6-COOH, and HS-EG3 during SAM formation allowed for control over the densities of each peptide on the substrate. Substrates presenting varying surface densities of RGESP (a nonfunctional peptide), RGDSP (a cell adhesion peptide), or TYRSRKY (a heparin/heparan sulfate-binding peptide) were then used to characterize the relationship between peptide surface density and human mesenchymal stem cell (hMSC) adhesion. Results demonstrate that RGESP does not influence RGDSP-mediated adhesion of hMSCs, which indicates that a second peptide with distinct bioactivity can be immobilized alongside RGDSP to characterize the influence of two peptides on hMSC behavior. Our results also demonstrate that RGDSP and TYRSRKY act synergistically to promote hMSC adhesion in the absence of serum. Interestingly, heparin sequestered by TYRSRKY inhibits cell adhesion on substrates presenting RGDSP = 0.1% and > or = 0.1% TYRSRKY or RGDSP = 1% and > or = 0.5% TYRSRKY. Taken together, these results indicate that two peptides can be controllably presented to stem cells on the same otherwise bioinert SAM substrate, and that multiple, distinct extracellular moieties act in concert to regulate hMSC adhesion. PMID- 20353154 TI - Isomerization mechanisms of stereolabile tris- and bis-bidentate octahedral cobalt(II) complexes: X-ray structure and variable temperature and pressure NMR kinetic investigations. AB - The isomerization dynamics of five labile octahedral Co(II) compounds have been investigated by variable temperature and pressure (1)H and (19)F NMR spectroscopy in dichloromethane solution. The X-ray crystal structure of the two tris chelates, [Co(HFA)(2)bpic] (1) and [Co(TTFA)(2)bpy] (2), show a distorted octahedral arrangement of the 4 oxygen and 2 nitrogen donor atoms, with bidentate ligand bite angles smaller than 90 degrees. On the other hand, in the three bis chelates, trans(N)-[Co(HFA)(2)(CH(3)py)(2)](3), cis(N)-cis(CF(3))-trans(S) [Co(TTFA)(2)(CH(3)py)(2)](4), and trans(N)-trans(CF(3)) [Co(TTFA)(2)(CF(3)py)(2)](5), the replacement of the bidentate nitrogen donor ligands by two monodentate Rpy ligands leads to relaxed structures with almost regular octahedral arrangements of the donor atoms (HFA = 1,1,1,5,5,5-hexafluoro 2,4-pentanedionato anion; TTFA = 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedionato anion; bpy = 2,2'-bipyridine; bpic = 4,4'-dimethyl-2,2'-bipyridine). In solution the five complexes are stereolabile and all possible isomers are formed: from one for 1 up to five for 4 and 5. All cis-N isomers form pairs of enantiomers, whereas the trans-N isomers are achiral. A solid state structure/isomerization mechanism/rate correlation has been established for the isomerization dynamics of these Co(II) tris- and bis-chelates. The two tris-chelate complexes 1 and 2, with a distorted octahedral solid state structure, show one and three isomers in solution and isomerize/tautomerize very rapidly according to Bailar twist mechanisms. The three bis-chelate complexes 3, 4, and 5, with a close to octahedral symmetry in the solid state, show two, five, and five isomers, respectively. They isomerize/tautomerize 3 orders of magnitude slower as the tris chelates, by an intramolecular dissociative mechanism involving a ring-opening of an arm of a bidentate ligand to form a TBP intermediate with a dangling bidentate ligand. The results of this first systematic investigation of the isomerization mechanisms of highly labile Co(II) complexes are supported by the NMR observed exchange paths (up to five for complexes for 4 and 5), the variable temperature (185 to 312 K) and pressure (up to 200 MPa) activation parameters, and a detailed analysis of the solid state structures. PMID- 20353155 TI - Formation of aminoxy and oxo complexes from the reaction of Nb(NMe2)5 with O2 and the crystal structure of Nb(NEt2)5. AB - The reaction of Nb(NMe(2))(5) with O(2) gives three complexes: monomeric (Me(2)N)(n)Nb(eta(2)-ONMe(2))(5-n) (n = 3, 4) and dimeric (Me(2)N)(4)Nb(2)[eta(2) N(Me)CH(2)NMe(2)](2)(mu-O)(2). Nb(NEt(2))(5) was prepared in a mixture of pentane and THF, leading to its purification and characterization by single-crystal X-ray diffraction. Unlike Nb(NMe(2))(5), which adopts a square pyramidal structure, Nb(NEt(2))(5) is a distorted trigonal bipyramid. The reaction of Nb(NEt(2))(5) with O(2) gives an insoluble white solid. PMID- 20353156 TI - Both visual and fluorescent sensor for Zn2+ based on quinoline platform. AB - A fluorescent Zn(2+) sensor 2-(hydroxymethyl)-4-methyl-6-((quinolinyl-8 imino)methyl)phenol (HMQP) based on the 8-aminoquinoline platform has been synthesized. This sensor displays high selectivity, sensitive fluorescence enhancement, strong binding ability, and ratiometric response to Zn(2+) in Tris HCl (50 mM, pH 7.54), THF-H(2)O (9:1, v/v). And an obvious color change between HMQP and Zn(2+)-MQP(-) can be visually observed by the naked eye. The composition of the complex Zn(2+)-MQP(-) has been found to be 1:2 based on the fluorescence/absorption titration and further confirmed by X-ray crystallography. PMID- 20353157 TI - pH Gradient as a tool for the separation of ionizable analytes in reversed-phase high-performance chromatography. AB - The aim of this work was to propose a general scheme of optimizing separation of ionizable analytes and to determine conditions of maximal peak compression in pH gradient reversed-phase high-performance liquid chromatography (RP HPLC). The approximated explicit equation of the linear pH gradient has been developed. It allows predicting retention times for a given organic modifier content, initial value of pH, and the start and steepness of the pH gradient. Also the formula for calculating maximal peak compression is provided. The developed theory was compared with experimental data on the example of a weak acid (ketoprofen) and a weak base (papaverine). Five parameters characterizing analyte retention (log k(w) and S of the ionized and nonionized forms along with pK(a,chrom)) were determined in a series of isocratic experiments carried out at different pH values and with different methanol contents in the eluent. Next, a series of pH gradients of different pH-gradient steepness and of different pH-gradient starting time has been obtained and used to test the validity of our theoretical approach. The conditions of maximal peak width compression have been found. The derived theory was proved to be in a good agreement with the experimental data. The pH-gradient method led to peak compression of up to 0.2, and minimized peak tailing was obtained for the tested analytes. Since the majority of analytical separations are done in an isocratic mode we proposed a means to transfer an isocratic method to a pH-gradient method. PMID- 20353158 TI - Application of a nonradioactive pulsed electron source for ion mobility spectrometry. AB - Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. Common ion mobility spectrometers work by employing a radioactive source to provide electrons with high energy to ionize analytes in a series of chemical reactions. General security as well as regulatory concerns related to radioactivity result in the need for a different ionization source which on the other hand produces ions in a similar manner as a radioactive source since the ion chemistry is well known. Here we show the application of a novel nonradioactive source that produces spectra similar to those obtained with radioactive tritium sources. Using this source in a pulsed mode offers the additional advantage of selecting certain analytes by their recombination time and thus significantly increasing the selectivity. The successful isolation of a target signal in the presence of contaminants using a pulsed electron beam or more precisely the difference in recombination times will be demonstrated for the case of dimethyl methylphosphonate (DMMP) showing the potential of this source to reduce the possibility for false-positive detection of corresponding chemical warfare agents (CWA) by IMS. PMID- 20353159 TI - Differential scanning fluorimetry measurement of protein stability changes upon binding to glycosaminoglycans: a screening test for binding specificity. AB - The interaction between glycosaminoglycans (GAGs) and proteins is important for the regulation of protein transport and activity. Here we present a novel method for the measurement of protein-GAG interactions suitable for high-throughput screening, able to discriminate between the interactions of a protein with GAGs of different structures. Binding of proteins to the GAG heparin, a proxy for sulfated regions of extracellular heparan sulfate, was found to enhance the stability of three test proteins, fibroblast growth factors (FGFs)-1, -2, and 18. Chemically modified heparins and heparin oligosaccharides of different lengths stabilized the three FGFs to different extents, depending on the pattern of sugar binding specificity. The method is based on a differential scanning fluorescence approach. It uses a Sypro Orange dye, which binds to exposed core residues of a denatured protein and results in an increased fluorescence signal. It is convenient, requiring low micromolar amounts of protein and ligand compared to other interaction assays, employing only a real-time polymerase chain reaction (PCR) instrument. PMID- 20353160 TI - Internal energies of ion-sputtered neutral tryptophan and thymine molecules determined by vacuum ultraviolet photoionization. AB - Vacuum ultraviolet photoionization coupled to secondary neutral mass spectrometry (VUV-SNMS) of deposited tryptophan and thymine films are performed at the Chemical Dynamics Beamline. The resulting mass spectra show that while the intensity of the VUV-SNMS signal is lower than the corresponding secondary ion mass spectroscopy (SIMS) signal, the mass spectra are significantly simplified in VUV-SNMS. A detailed examination of tryptophan and thymine neutral molecules sputtered by 25 keV Bi(3)(+) indicates that the ion-sputtered parent molecules have approximately 2.5 eV of internal energy. While this internal energy shifts the appearance energy of the photofragment ions for both tryptophan and thymine, it does not change the characteristic photoionizaton efficiency (PIE) curves of thymine versus photon energy. Further analysis of the mass spectral signals indicate that approximately 80 neutral thymine molecules and 400 tryptophan molecules are sputtered per incident Bi(3)(+) ion. The simplified mass spectra and significant characteristic ion contributions to the VUV-SNMS spectra indicate the potential power of the technique for organic molecule surface analysis. PMID- 20353161 TI - High-precision measurement and analysis of colloidal monolayers. AB - This technical note describes an imaging algorithm for analyzing colloidal monolayers, including the measurement of particle-to-particle distances with nanometer-scale resolution and the automated detection of defects and edges, as well as determining the uniformity of the colloid size distribution. The algorithm also allows for the automatic detection and measurement of scaling introduced by nonsquare detector pixels, a common problem in imaging. As an application, we demonstrate the use of this method for spatially calibrating digital video microscopy systems that can be applied in situations where conventional methods may be inappropriate. Here, we provide an overview of the workings of the algorithm, which we have made freely available. PMID- 20353162 TI - Multivariate curve resolution analysis for interpretation of dynamic Cu K-edge X ray absorption spectroscopy spectra for a Cu doped V(2)O(5) lithium battery. AB - Vanadium pentoxide materials prepared through sol-gel processes act as excellent intercalation hosts for lithium as well as polyvalent cations. A chemometric approach has been applied to study the X-ray absorption near-edge structure (XANES) evolution during in situ scanning of the Cu(0.1)V(2)O(5) xerogel/Li ions battery. Among the more common techniques, the fixed size windows evolving factor analysis (FSWEFA) permits the number of species involved in the experiment to be determined and the range of existence of each of them. This result, combined with the constraints of the invariance of the total concentration and non-negativity of both concentrations and spectra, enabled us to obtain the spectra of the pure components using a multivariate curve resolution refined by an alternate least squares fitting procedure. This allowed the normalized concentration profile to be understood. This data treatment evidenced the occurrence, for the first time, of three species during the battery charging. This fact finds confirmation by comparison of the pure spectra with the experimental ones. Extended X-ray absorption fine structure (EXAFS) analysis confirms the occurrence of three different chemical environments of Cu during battery charging. PMID- 20353163 TI - Model updating for spectral calibration maintenance and transfer using 1-norm variants of Tikhonov regularization. AB - In this study, calibration maintenance confronts the problem of updating a model developed in the primary condition to accurately predict the calibrated analyte in samples measured in new secondary conditions. Calibration transfer refers to updating a model based on a primary instrument to predict samples measured on new secondary instruments. A 2-norm variant of Tikhonov regularization (TR) has been used with spectroscopic data to perform calibration maintenance and transfer where just a few samples measured in the secondary condition/instrument are augmented to the primary calibration data to update the primary model. To achieve improved predictions, in this paper we report on 1-norm penalties to create two novel variants of TR for model updating. To solve the multiple penalty minimization numerical problems involved with the new TR variants, data transformation processes are applied, allowing a least absolute shrinkage and selection operator type algorithm to be implemented. Near-infrared spectra measured under two different temperatures represent the calibration maintenance application, and near-infrared spectra measured on two instruments denote the calibration transfer situation. Compared to TR in the recently developed 2-norm penalty mode, validation sample prediction errors are reduced when the 1-norm TR variant that selects wavelengths is used. PMID- 20353164 TI - SPR Biosensing in crude serum using ultralow fouling binary patterned peptide SAM. AB - Near-zero fouling monolayers based on binary patterned peptides allow low nanomolar detection of the matrix metalloproteinase-3 (MMP-3) directly in crude bovine serum, without sample pretreatment, secondary antibody detection or signal amplification. The peptide 3-MPA-HHHDD-OH (3-MPA, 3-mercaptopropionic acid) was found optimal compared to other binary patterned peptides based on 3-MPA-A(x) B(y)-OH, where 0 X(-) + PhX (Ph = phenyl)- shows the following approximate trend: NH(2)(-) approximately OH(-) approximately F(-) >> PH(2)(-) approximately SH(-) approximately Cl(-) > AsH(2)(-) approximately SeH(-) approximately Br(-). The periodic trends are discussed in terms of molecular properties (proton affinity of X(-) expressing Lewis basicity of the nucleophile and C(1s) orbital energy expressing Lewis acidity of the substrate) based on a dative bonding model. Furthermore, the stepwise progress of the reactions and the critical structures are analyzed applying energy decomposition analysis. Increased stability, and thereby increased intrinsic nucleophilicity, correlates with decreasing aromatic character of the Meisenheimer structure. This apparent contradiction is explained in consistency with the other observations using the same model. PMID- 20353178 TI - Photoinduced tandem reactions of isoquinoline-1,3,4-trione with alkynes to build aza-polycycles. AB - Photoinduced tandem reactions of isoquinoline-1,3,4-triones (3) with azaaryl substituted acetylenes (4a-4o) are described as an efficient method to build novel aza-polycycles. Most of the reactions proceeded via the tandem reaction sequence of photoinduced [2 + 2] cycloaddition (the Paterno-Buchi reaction) oxetene electrocyclic ring opening-hexatriene to phenanthrene type electrocyclization-oxidative dehydrogenation. Using these photo tandem reactions of isoquinolinetrione with acetylenes substituted by different azaaryl rings including pyridine, pyrimidine, pyrazine, and quinoline, we were able to obtain diverse aza-polycyclic frameworks with isoquinolinedione fused with naphthalene, quinoline or isoquinoline, quinazoline, quinoxaline, and phenanthridine, respectively, with yields up to 85%. Regioselectivity of the [2 + 2] photocycloadditions and the electrocyclization reactions in the reaction sequence that leads to the formation of different aza-polycyclic ring systems is discussed. Changing the other substitution group on the azaaryl substituted acetylenes from benzene to pyridine or cyclopropane resulted in acetylenes with different photoreactivities with isoquinolinetrione and improved regioselectivity to form single aza-polycyclic products. PMID- 20353179 TI - Probing the ternary complexes of indoleamine and tryptophan 2,3-dioxygenases by cryoreduction EPR and ENDOR spectroscopy. AB - We have applied cryoreduction/EPR/ENDOR techniques to characterize the active site structure of the ferrous-oxy complexes of human (hIDO) and Shewanella oneidensis (sIDO) indoleamine 2,3-dioxygenases, Xanthomonas campestris (XcTDO) tryptophan 2,3-dioxygenase, and the H55S variant of XcTDO in the absence and in the presence of the substrate L-Trp and a substrate analogue, L-Me-Trp. The results reveal the presence of multiple conformations of the binary ferrous-oxy species of the IDOs. In more populated conformers, most likely a water molecule is within hydrogen-bonding distance of the bound ligand, which favors protonation of a cryogenerated ferric peroxy species at 77 K. In contrast to the binary complexes, cryoreduction of all of the studied ternary [enzyme-O(2)-Trp] dioxygenase complexes generates a ferric peroxy heme species with very similar EPR and (1)H ENDOR spectra in which protonation of the basic peroxy ligand does not occur at 77 K. Parallel studies with L-Me-Trp, in which the proton of the indole nitrogen is replaced with a methyl group, eliminate the possibility that the indole NH group of the substrate acts as a hydrogen bond donor to the bound O(2), and we suggest instead that the ammonium group of the substrate hydrogen bonds to the dioxygen ligand. The present data show that substrate binding, primarily through this H-bond, causes the bound dioxygen to adopt a new conformation, which presumably is oriented for insertion of O(2) into the C(2) C(3) double bond of the substrate. This substrate interaction further helps control the reactivity of the heme-bound dioxygen by "shielding" it from water. PMID- 20353180 TI - Formation of beyerene, kaurene, trachylobane, and atiserene diterpenes by rearrangements that avoid secondary carbocations. AB - Quantum chemical calculations on carbocation intermediates encountered during the conversion of ent-copalyl diphosphate to the diterpenes beyerene, kaurene, trachylobane, and atiserene are described. Based on the results of these computations, it is suggested that previously proposed secondary carbocation intermediates are avoided. In some cases, complex rearrangements in which up to three alkyl or hydride shifting events are coupled into concerted processes are predicted to occur instead. The potential effects of electron-rich active site groups on the inherent reactivity of key carbocations are discussed, as are complex rearrangements coupled to deprotonation events. Based on computed electrostatic potential maps, it also is proposed that ammonium ions that were previously designed as mimics of several carbocations are actually better mimics of transition state structures for carbocation deprotonation. PMID- 20353181 TI - Chemically controlled protein assembly: techniques and applications. PMID- 20353183 TI - Detection of melamine in milk powder and human urine. AB - Detection of melamine has been developed by employing oxidized polycrystalline gold electrode (poly GE). The poly GE was directly utilized for the detection of melamine using differential pulse voltammetry (DPV) and impedimetry. Poly GE successfully showed the oxidation peak for melamine adsorption at 1.1 V is purely based on the detection of adsorption signals of melamine at the electrode surface. Furthermore, the melamine adsorbed poly GE surface has been studied using atomic force microscopy (AFM). Poly GE successfully detects the oxidation signals of melamine in the linear range of 0.05-1.31 ppm in laboratory samples. The proposed poly GE successfully detects the melamine signal (0.06-0.85 ppm) in tainted milk powder samples. It also exhibits two well-separated anodic oxidation peaks for urine and melamine in melamine-spiked human urine samples. Gas chromatography-mass spectrometry (GC-MS) was also employed for the successful detection of melamine in the above proposed real samples. PMID- 20353182 TI - Interfacial properties of apolipoprotein B292-593 (B6.4-13) and B611-782 (B13 17). Insights into the structure of the lipovitellin homology region in apolipoprotein B. AB - The N-terminal sequence of apolipoprotein B (apoB) is critical in triacylglycerol rich lipoprotein assembly. The first 17% of apoB (B17) is thought to consist of three domains: B5.9, a beta-barrel, B6.4-13, a series of 17 alpha-helices, and B13-17, a putative beta-sheet. B5.9 does not bind to lipid, while B6.4-13 and B13 17 contain hydrophobic interfaces that can interact with lipids. To understand how B6.4-13 and B13-17 might interact with triacylglycerol during lipoprotein assembly, the interfacial properties of both peptides were studied at the triolein/water interface. Both B6.4-13 and B13-17 are surface active. Once bound, the peptides can be neither exchanged nor pushed off the interface. Some residues of the peptides can be ejected from the interface upon compression but readsorb on expansion. B13-17 binds to the interface more strongly. The maximum pressure the peptide can withstand without being partially ejected (Pi(max)) is 19.2 mN/m for B13-17 compared to 16.7 mN/m for B6.4-13. B13-17 is purely elastic at the interface, while B6.4-13 forms a viscous-elastic film. When they are spread at an air/water interface, the limiting area and the collapse pressures are 16.6 A(2)/amino acid and 31 mN/m for B6.4-13 and 17.8 A(2)/amino acid and 35 mN/m for B13-17, respectively. The alpha-helical B6.4-13 contains some hydrophobic helices that stay bound and prevent the peptide from leaving the surface. The beta-sheets of B13-17 bind irreversibly to the surface. We suggest that during lipoprotein assembly, the N-terminal apoB starts recruiting lipid as early as B6.4, but additional sequences are essential for formation of a lipid pocket that can stabilize lipoprotein emulsion particles for secretion. PMID- 20353184 TI - Ab initio EOM-CCSD investigation of one-bond C-C, N-C, and N-N spin-spin coupling constants in fluoroazines. AB - Ab initio EOM-CCSD calculations were carried out to examine one-bond (1)J (C-C), (1)J(N-C), and (1)J(N-N) spin-spin coupling constants in benzene, pyridine, the diazines, and selected triazines, tetrazines, and pentazine and their fluoro substituted derivatives. Relative to benzene, (1)J(C-C) decreases in the azines as N atoms are introduced into the ring, but this decrease does not exceed 5 Hz. In the fluoro-substituted derivatives, (1)J(C-C) may increase only slightly if the coupled carbon atoms form C-H bonds, or increase dramatically if either or both of the coupled atoms participate in C-F bonds. The value of (1)J(C-C) also depends on the nature of the bonding of the coupled atoms in the ring. The largest increase is found when both carbons participate in C-F bonds, and both are ortho to N atoms. Relative to pyridine, (1)J(N-C) increases as N atoms are introduced into the ring, with the magnitude of the increase depending on the bonding of the coupled atoms. It is negligible if neither atom is bonded to another N, increases if one of the coupled atoms is bonded to another N atom, and increases further if both are bonded to other N atoms. Fluoro-substitution has an opposing effect on (1)J(N-C), making this coupling constant less positive or negative when the coupled C participates in a C-F bond. The decrease in (1)J(N-C) relative to the parent molecule is enhanced if either of the coupled atoms is bonded to another N atom or to another C-F group. A further enhancement occurs if both coupled atoms are so bonded, with the largest increases associated with the bonding scheme in which the coupled C is bonded to another N and the coupled N to another C-F. Fluoro-substitution has a small effect on (1)J(N-C) if the coupled C forms a C-H bond, and on (1)J(N-N). Thus, the effects of fluoro-substitution on one-bond couplings tend to be localized. PMID- 20353185 TI - Scaling of computed cyano-stretching frequencies and IR intensities of nitriles, their anions, and radicals. AB - Specialized scale factors and scaling equations have been determined for both cyano stretching vibrational frequencies and IR intensities of nitrile molecules, anions and radicals (269 data points in all). Various double and triple-zeta basis sets, viz. 3-21G, 6-31G, 6-311G, 6-31G*, 6-311G*, 6-31+G, 6-311+G, 6-31G**, 6-31+G*, 6-311+G*, 6-31++G**, 6-311++G**, and aug-cc-pVDZ at the B3LYP and HF theory levels have been applied. Besides the theory and basis set, the mean deviations between scaled computed and experimental spectroscopic features have been found to depend also on the series studied: frequencies or intensities, and molecules, anions, or radicals. Use of scaling equations instead of scale factors has given slightly worse results for frequencies, but essentially better ones for infrared intensities. PMID- 20353186 TI - Interaction and dimerization energies in methyl-blocked alpha,gamma-peptide nanotube segments. AB - The building blocks of a promising class of peptide nanotubes composed of alternating D-alpha-amino acids and (1R,3S)-3-aminocyclohexane (or cyclopentane) carboxylic acid (D-gamma-Ach or D-gamma-Acp) were explored by computational methods. Specifically, density functional theory (DFT) calculations on monomers and dimers of gamma-Ach-based and gamma-Acp-based alpha,gamma-cyclo-hexapeptides and cyclo-octapeptides were carried out to investigate the experimentally observed preference for alpha-alpha over gamma-gamma dimerization, associated with the two types of stacking patterns present in these peptide nanotubes, as well as the preference for heterodimerization versus homodimerization. Full geometry optimizations were performed at the B3LYP/6-31G(d) level, and single point calculations were subsequently carried out with the B3LYP and M05-2X functionals and the 6-31+G(d,p) basis set. The calculations predict that the interaction energies in the alpha-alpha species are quite similar to those in the gamma-gamma dimers. However, a comparison of dimerization energies (i.e., interaction energies plus deformation energies of monomers) shows that alpha alpha dimerization is energetically favored over gamma-gamma dimerization. The calculations strongly suggest that the preference for alpha-alpha binding is governed by differences between the deformation energies in the alpha and gamma monomers, rather than by differences between the relative strengths of the alpha alpha and gamma-gamma hydrogen-bonding patterns. Calculations based on local properties of the electron density support the previous suggestion that the H-N bonds of the alpha-amino acids are more polarized than those of the gamma-amino acids. PMID- 20353187 TI - Structural characterization of mutations at the oxygen activation site in monomeric sarcosine oxidase . AB - Oxygen reduction and sarcosine oxidation in monomeric sarcosine oxidase (MSOX) occur at separate sites above the si- and re-faces, respectively, of the flavin ring. Mutagenesis studies implicate Lys265 as the oxygen activation site. Substitution of Lys265 with a neutral (Met, Gln, or Ala) or basic (Arg) residue results in an approximately 10(4)- or 250-fold decrease, respectively, in the reaction rate. The overall structure of MSOX and residue conformation in the sarcosine binding cavity are unaffected by replacement of Lys265 with Met or Arg. The side chain of Met265 exhibits the same configuration in each molecule of Lys265Met crystals and is nearly congruent with Lys265 in wild-type MSOX. The side chain of Arg265 is, however, dramatically shifted ( approximately 4-5 A) compared with Lys265, points in the opposite direction, and exhibits significant conformational variability between molecules of the same crystal. The major species in solutions of Lys265Arg is likely to contain a "flipped-out" Arg265 and exhibit negligible oxygen activation, similar to Lys265Met. The 400-fold higher oxygen reactivity observed with Lys265Arg is attributed to a minor (<1%) "flipped in" Arg265 conformer whose oxygen reactivity is similar to that of wild-type MSOX. A structural water (WAT1), found above the si-face of the flavin ring in all previously determined MSOX structures, is part of an apparent proton relay system that extends from FAD N(5) to bulk solvent. WAT1 is strikingly absent in Lys265Met and Lys265Arg, a feature that may account for the apparent kinetic stabilization of a reductive half-reaction intermediate that is detectable with the mutants but not wild-type MSOX. PMID- 20353189 TI - Scanning the potential energy surface of furanosyl oxocarbenium ions: models for reactive intermediates in glycosylation reactions. AB - A new scanning method with complementary graph to describe the ring potential energy surface of furanoses is introduced. Density functional theory at the B3LYP level of theory with the 6-311G(d,p) basis set is used to calculate the energy of the partially minimized structures. The method is used to determine the correlation between the preferred conformation of oxocarbenium ions that are model intermediates for a glycosylation reaction and recent experimental results. Key disagreements between the predicted geometry and the minima based on the scans described herein indicate that the preferred oxocarbenium ion conformation is not a consistent predictor of preferred stereochemistry of the products. PMID- 20353188 TI - Recognition of (2S)-aminomalonyl-acyl carrier protein (ACP) and (2R) hydroxymalonyl-ACP by acyltransferases in zwittermicin A biosynthesis. AB - Polyketide synthases elongate a polyketide backbone by condensing carboxylic acid precursors that are thioesterified to either coenzyme A or an acyl carrier protein (ACP). Two of the three known ACP-linked extender units, (2S) aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP, are found in the biosynthesis of the agriculturally important antibiotic zwittermicin A. We previously reconstituted the formation of (2S)-aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP from the primary metabolites l-serine and 1,3-bisphospho-d-glycerate. In this report, we characterize the two acyltransferases involved in the specific transfer of the (2S)-aminomalonyl and (2R)-hydroxymalonyl moieties from the ACPs associated with extender unit formation to the ACPs integrated into the polyketide synthase. This work establishes which acyltransferase recognizes each extender unit and also provides insight into the substrate selectivity of these enzymes. These are important step toward harnessing these rare polyketide synthase extender units for combinatorial biosynthesis. PMID- 20353190 TI - Rheological and fluorescence investigation of interaction between hexadecyltrimethylammonium bromide and methylcellulose in the presence of hydrophobic salts. AB - The interaction of hexadecyltrimethylammonium bromide (HTAB) and methylcellulose (MC) has been investigated in aqueous medium employing rheological and fluorescence probing experiments. The associated physicochemical properties of the polymer-surfactant mixed system such as critical aggregation concentration (cac), critical micelle concentration (cmc), micellar aggregation number (N), micellar micropolarity index (pyrene I(1)/I(3) values), and viscosity curve are studied as a function of HTAB concentration. The effects of sodium benzoate (NaBz), sodium hexanoate (NaHx) and sodium chloride (NaCl) on the behavior of the polymer-surfactant solution have been followed systematically. The obtained experimental findings unfold significant information with respect to the effects of the salts on the solution behavior of the mixed system in addition to gelation characteristics. PMID- 20353191 TI - Quantitative enzyme activity determination with zeptomole sensitivity by microfluidic gradient-gel zymography. AB - We describe a sensitive zymography technique that utilizes an automated microfluidic platform to report enzyme molecular weight, amount, and activity (including k(cat) and K(m)) from dilute protein mixtures. Calf intestinal alkaline phosphatase (CIP) is examined in detail as a model enzyme system, and the method is also demonstrated for horseradish peroxidase (HRP). The 40 min assay has a detection limit of 5 zmol ( approximately 3 000 molecules) of CIP. Two-step pore-limit electrophoresis with enzyme assay (PLENZ) is conducted in a single, straight microchannel housing a polyacrylamide (PA) pore-size gradient gel. In the first step, pore limit electrophoresis (PLE) sizes and pseudoimmobilizes resolved proteins. In the second step, electrophoresis transports both charged and neutral substrates into the PLE channel to the entrapped proteins. Arrival of substrate at the resolved enzyme band generates fluorescent product that reveals enzyme molecular weight against a fluorescent protein ladder. Additionally, the PLENZ zymography assay reports the kinetic properties of CIP in a fully quantitative manner. In contrast to covalent enzyme immobilization, physical pseudoimmobilization of CIP in the PA gel does not significantly reduce its maximum substrate turnover rate. However, an 11-fold increase in the Michaelis constant (over the free solution value) is observed, consistent with diffusional limitations on substrate access to the enzyme active site. PLENZ offers a robust platform for rapid and multiplexed functional analysis of heterogeneous protein samples in drug discovery, clinical diagnostics, and biocatalyst engineering. PMID- 20353193 TI - Multiple pharmacophore models combined with molecular docking: a reliable way for efficiently identifying novel PDE4 inhibitors with high structural diversity. AB - Multiple pharmacophore models were constructed based on the 18 crystal structures of phosphodiesterase 4 (PDE4) in complex with different inhibitors for discovering new potential PDE4 inhibitors. After validation of their efficiency in screening, 10 of the pharmacophore models were confirmed effective. Remarkably, the hits retrieved by these effective pharmacophore models were different, demonstrating that different pharmacophore models may have different performances in database screening. Therefore, all these models were employed to screen the compound database SPECS for finding potent leads with much structural diversity. Combining all the screened hits based on the 10 pharmacophore models, followed by molecular docking and bioassay, 4 of 53 tested compounds were found as active as rolipram (a well studied PDE4 inhibitor). More impressively, the four potent inhibitors with different chemical scaffolds were discovered by three different pharmacophore models separately, suggesting that a single pharmacophore model-based screening might not be efficient in thoroughly identifying potential hits from a compound database. This study also revealed that ligand-receptor complex structure-based pharmacophore is more efficient for identifying potent hits with great structural diversity in comparison with ligand-based pharmacophore and similarity search approaches. Therefore, multiple pharmacophore model-based virtual screenings should be used, if available, in combination with molecular docking for fully discovering hit compounds from compound databases. PMID- 20353194 TI - Structure and anti-TB activity of trachylobanes from the liverwort Jungermannia exsertifolia ssp. cordifolia. AB - In the critical search for new antituberculosis lead compounds, bryophytes represent a largely untapped resource of chemically diverse structures. From the liverwort Jungermannia exsertifolia subsp. cordifolia, 11 new trachylobane diterpene derivatives, as well as three known compounds, were isolated. Their structures were elucidated by spectroscopic means, and full (1)H NMR spin analysis of one model compound confirmed the relative configurational assignments of the congeners. Four of the isolates exhibited noticeable activity against virulent Mycobacterium tuberculosis H(37)Rv with minimal inhibitory concentrations of 61-24 microg/mL. This finding suggests that bryophytes in general and trachylobanes in particular deserve further attention in the search for new antimycobacterial leads. PMID- 20353196 TI - Optically-driven collapse of a plasmonic nanogap self-monitored by optical frequency mixing. AB - A nanoparticle separated from a metallic surface by a few-nanometer thick polymer layer forms a nanoscale junction, or nanogap. Illuminating this structure with ultrashort optical pulses, exciting the plasmon resonance, results in a continuous, monitorable collapse of the nanogap. The four-wave mixing signal generated by this illumination of the nanogap provides a simultaneous monitoring of the collapse, increasing dramatically upon gap closure. Collapse is irreversible, occurring with simultaneous ablation of the dielectric from the junction. PMID- 20353195 TI - Converse piezoelectric effect in cellulose I revealed by wide-angle X-ray diffraction. AB - The converse piezoelectric effect in cellulose I was studied by exposing thin pine wood slices to an electric field. Macroscopically, a strong extension of wood was observed in its transverse anatomical direction (grain angle 90 degrees), perpendicular to the direction of the electric field. The same effect, albeit to a lesser extent, was observed for specimens with a 45 degree grain angle, whereas no measurable dimensional change was observed for specimens with grain oriented parallel to the testing direction (0 degree grain angle). The measured extension in the transverse direction was proportional to the intensity of the applied electric field and amounted to 0.0278% on average at a field intensity of 1 MV m(-1), which results in a piezoelectric charge constant of 278 pm V(-1). At the nanoscale, changes in the cellulose crystallites due to the applied electric field were studied by means of wide-angle X-ray diffraction using the same specimens as in macroscopic experiments. Significant radial shifts of the scattering intensity peak attributed to the cellulose 200 crystallographic plane toward smaller scattering angles were observed, while the electric field was applied. These peak shifts were attributed to an increase in the spacing of the 200 crystallographic planes of cellulose I. At an electric field intensity of 1 MV m(-1), a crystallite strain epsilon(perpendicular 200) normal to the 200 reflection plane of 0.2% was estimated from Bragg's law. PMID- 20353197 TI - Contrasting intermolecular and intramolecular exciplex formation of a 1,4-dicyano 2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad. AB - An intramolecular exciplex is formed upon excitation of the cyclohexane solution of the 1,4-dicyano-2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad, but little if any intramolecular CT complex exists in the ground state of this substance in solution. In contrast, in the crystalline state, the dyad forms an intermolecular mixed-stack CT complex in the ground state and an intermolecular exciplex when it is photoexcited. PMID- 20353198 TI - Investigating the nature of noble gas-copper bonds by the quantum theory of atoms in molecules. AB - We investigated noble gas-copper bonds in linear complexes represented by the NgCuX general formula in which Ng and X stand for a noble gas (neon, argon, krypton, or xenon) and a halogen (fluorine, chlorine or bromine), respectively, by coupled cluster methods and modified cc-pVQZ basis sets. The quantum theory of atoms in molecules (QTAIM) shows a linear relation between the dissociation energy of noble gas-copper bonds and the amount of electronic charge transferred mainly from the noble gas to copper during complexation. Large changes in the QTAIM quadrupole moments of copper and noble gases resulting from this bonding and a comparison between NgCuX and NgNaCl systems indicate that these noble gas copper bonds should be better interpreted as predominantly covalent. Finally, QTAIM atomic dipoles of noble gases in NgNaCl systems agree satisfactorily with atomic dipoles given by a simple model for these NgNa van der Waals bonds. PMID- 20353199 TI - Electron and hole dynamics in dye-sensitized solar cells: influencing factors and systematic trends. AB - We investigate electron and hole dynamics upon photon excitation in dye sensitized solar cells, using a recently developed method based on real-time evolution of electronic states through time-dependent density functional theory. The systems we considered consist of organic sensitizers and nanocrystalline TiO(2) semiconductors. We examine the influence of various factors on the dynamics of electrons and holes, including point defects (vacancies) on the TiO(2) surface, variations in the dye molecular size and binding geometry, and thermal fluctuations which result in different alignments of the electronic energy levels. Two clear trends emerge: (a) dissociated adsorption of the dye molecules leads to faster electron injection dynamics by reducing interfacial dipole moments; (b) oxygen vacancy defects stabilize dye adsorption and facilitate charge injection, at the cost of lower open circuit voltage and higher electron-hole recombination rate. Understanding of these effects at the atomic level suggests tunable parameters through which the electronic characteristics of dye-sensitized solar cell devices can be improved and their efficiency can be maximized. PMID- 20353200 TI - Vibrational spectroscopy of intermediates in methane-to-methanol conversion by FeO(+). AB - Gas phase FeO(+) can convert methane to methanol under thermal conditions. Two key intermediates of this reaction are the [HO-Fe-CH(3)](+) insertion intermediate and Fe(+)(CH(3)OH) exit channel complex. These intermediates are selectively formed by reaction of laser-ablated Fe(+) with organic precursors under specific source conditions and are cooled in a supersonic expansion. Vibrational spectra of the sextet and quartet states of the intermediates in the O-H and C-H stretching regions are measured by infrared multiple photon dissociation of Fe(+)(CH(3)OH) and [HO-Fe-CH(3)](+) and by monitoring argon atom loss following irradiation of Fe(+)(CH(3)OH)(Ar) and [HO-Fe-CH(3)](+)(Ar)(n) (n = 1, 2). Analysis of the experimental results is aided by comparison with hybrid density functional theory computed frequencies. Also, an improved potential energy surface for the FeO(+) + CH(4) reaction is developed based on CCSD(T) and CBS-QB3 calculations for the reactants, intermediates, transition states, and products. PMID- 20353201 TI - Structure of [M + H - H(2)O](+) from protonated tetraglycine revealed by tandem mass spectrometry and IRMPD spectroscopy. AB - Multiple-stage tandem mass spectrometry and collision-induced dissociation were used to investigate loss of H(2)O or CH(3)OH from protonated versions of GGGX (where X = G, A, and V), GGGGG, and the methyl esters of these peptides. In addition, wavelength-selective infrared multiple photon dissociation was used to characterize the [M + H - H(2)O](+) product derived from protonated GGGG and the major MS(3) fragment, [M + H - H(2)O - 29](+) of this peak. Consistent with the earlier work [ Ballard , K. D. ; Gaskell , S. J. J. Am. Soc. Mass Spectrom. 1993 , 4 , 477 - 481 ; Reid , G. E. ; Simpson , R. J. ; O'Hair , R. A. J. Int. J. Mass Spectrom. 1999 , 190/191 , 209 -230 ], CID experiments show that [M + H - H(2)O](+) is the dominant peak generated from both protonated GGGG and protonated GGGG-OMe. This strongly suggests that the loss of the H(2)O molecule occurs from a position other than the C-terminal free acid and that the product does not correspond to formation of the b(4) ion. Subsequent CID of [M + H - H(2)O](+) supports this proposal by resulting in a major product that is 29 mass units less than the precursor ion. This is consistent with loss of HN horizontal lineCH(2) rather than loss of carbon monoxide (28 mass units), which is characteristic of oxazolone-type b(n) ions. Comparison between experimental and theoretical infrared spectra for a group of possible structures confirms that the [M + H - H(2)O](+) peak is not a substituted oxazolone but instead suggests formation of an ion that features a five-membered ring along the peptide backbone, close to the amino terminus. Additionally, transition structure calculations and comparison of theoretical and experimental spectra of the [M + H - H(2)O - 29](+) peak also support this proposal. PMID- 20353202 TI - Diversity of metal-ligand interactions in halide (X = I, Br, Cl, F) and halide free ambiphilic ligand rhodium complexes. AB - Reaction of the neutral ambiphilic ligand 2,7-di-tert-butyl-5-diphenylboryl-4 diphenylphosphino-9,9-dimethylthioxanthene (TXPB) with [{Rh(mu-Cl)(CO)(2)}(2)] yields [RhCl(CO)(TXPB)] (1) (Emslie et al. Organometallics 2006, 25, 5835). Complex 1 is square planar with the TXPB ligand bound to rhodium via the phosphine and thioether donors (these are features common to complexes 2-5, vide infra). Treatment of 1 with Me(3)SiBr and Me(3)SiI allowed for halide substitution to afford [RhBr(CO)(TXPB)] (2) and [RhI(CO)(TXPB)] (3), respectively. The halide co-ligands in complexes 1 and 2 form a strong bridging interaction between rhodium and the borane group in TXPB. The presence of stronger borane-halide coordination in 1 is clearly illustrated by an (11)B NMR chemical shift of 12 ppm versus 27 ppm in 2. In contrast, the iodide ligand in 3 forms only a weak bridging interaction to boron, leading to a B...I distance of 3.125(7) A, and an (11)B NMR chemical shift of 56 ppm (versus 69 ppm for free TXPB). A lower carbonyl stretching frequency in 3 (2002 cm(-1)) versus 1 or 2 (2008 and 2013 cm(-1), respectively) could be attributed to weakening of the Rh-X bond in 1 and 2 as a consequence of halide-borane coordination and/or a shorter Rh-S bond in complex 3. [Rh(CO)(TXPB-F)] (4) and the halide-free cation [Rh(CO)(TXPB)][PF(6)] (5) were accessed by reaction of 1 with [NMe(4)]F and Tl[PF(6)], respectively. Complex 4 is zwitterionic with fluoride bound to boron [(11)B NMR delta 4 ppm; B-F = 1.445(6) A; Rh...F = 3.261(3) A] and an eta(2) interaction between the cationic rhodium center and the ipso- and ortho-carbon atoms of a B-phenyl ring in TXPB-F. By contrast, rhodium in 5 engages in an eta(2)-interaction with boron and the ipso-carbon of one B-phenyl ring; Rh-B and Rh-C(ipso) bond lengths in 5 are 2.557(3) and 2.362(2) A, respectively. The long Rh-B distance and an (11)B NMR chemical shift of 57 ppm are consistent with only a weak Rh-B interaction in 5, and a CO stretching frequency of 2028 cm(-1) (Nujol), versus 2004-2013 cm(-1) for complexes 1-4, is indicative of greatly reduced electron density in 5, relative to 1-4. PMID- 20353203 TI - A C(2)-symmetric chiral bis-sulfoxide ligand in a rhodium-catalyzed reaction: asymmetric 1,4-addition of sodium tetraarylborates to chromenones. AB - A new C(2)-symmetric chiral bis-sulfoxide ligand, (R,R)-1,2-bis(tert butylsulfinyl)benzene, has been designed and prepared by the reaction of (R) benzyl tert-butylsulfoxide with (R)-thiosulfinate. This ligand exhibits excellent enantioselectivities in the Rh-catalyzed asymmetric 1,4-addition reaction. In particular, the present work has realized access to optically pure flavanones for the first time through 1,4-addition of arylboronic reagents to chromenones. PMID- 20353192 TI - Imaging and photodynamic therapy: mechanisms, monitoring, and optimization. PMID- 20353204 TI - Highly thermoconductive polymer nanocomposite with a nanoporous alpha-alumina sheet. AB - A highly thermoconductive insulative polymer nanocomposite with a nanoporous alpha-alumina sheet was reported. The thermal conductivity of the nanocomposite along the surface normal was 12 W m(-1) K(-1) (41 vol % alumina), a value as high as that predicted theoretically for a nanocomposite with thermoconductive fillers that form a perfectly connected thermoconductive network. The high thermal conductivity is probably due to the continuous alpha-alumina phase that functions as an efficient phonon path in the nanocomposite. The results suggest that the structure of the filler is important for the design of highly thermoconductive materials. PMID- 20353205 TI - Enzymatic conversion of atmospheric aldehydes into alcohol in a phospholipid polymer film. AB - We developed a unique method for converting atmospheric aldehyde into alcohol using formaldehyde dehydrogenase from Pseudomonas putida (PFDH) doped in a polymer film. A film of poly(2-methacryloyloxyethylphosphorylcholine-co-n-butyl methacrylate) (PMB), which has a chemical structure similar to that of a biological membrane, was employed for its biocompatibility. A water-incorporated polymer film entrapping PFDH and its cofactor NAD(+) was obtained by drying a buffered solution of PMB, PFDH, and NAD(+). The aldehydes in the air were absorbed into the polymer film and then enzymatically oxidized by PFDH doped in the PMB film. Interestingly, alcohol and carboxylic acid were produced by the enzymatic reaction, indicating that PFDH catalyzes dismutation of aldehyde in the PMB film. Importantly, a PFDH-PMB film catalyzes aldehyde degradation without consuming the nucleotide cofactor, thereby allowing repeated use of the film. The activity of PFDH in the PMB film was higher than that in other common water soluble polymers, suggesting that the hydrational state in a phospholipid polymer matrix is suitable for enzymatic activity. PMID- 20353206 TI - A new approach to fluorescence "turn-on" sensing of alpha-amino acids. AB - For the first time, a conjugated fluorescent polymer was utilized to probe alpha amino acids, sensitively and selectively, through a new approach. First the strong fluorescence of the prepared polyfluorene (P1) was quenched by trace copper ions, and then the quenched fluorescence was recovered upon the addition of alpha-amino acids, making P1 a new and sensitive biosensor toward alpha-amino acids. The experimental results demonstrated that the alpha-amino acid selective nature of P1 over other analytes was relatively good. Thus, the work reported here might open up a new avenue for developing new biosensors. PMID- 20353207 TI - Intersplat friction force and splat sliding in a plasma-sprayed aluminum alloy coating during nanoindentation and microindentation. AB - This study computes the friction force during splat sliding in the plasma-sprayed Al-Si coating based on the instrumented depth-sensing nanoindentation and microindentation experiments. A small intersplat friction force (approximately 10(-4) N) contributes to the occurrence of the splat sliding. As compared with nanoindentation, more and more splat sliding occurs during microindentation because of the increase in the applied load, which accounts for the approximately 26% loss of the elastic modulus. PMID- 20353208 TI - Smart nanofibers from combined living radical polymerization, "click chemistry", and electrospinning. AB - A simple method for preparing solvent-resistant nanofibers with a thermal sensitive surface has been developed by the combined technology of reversible addition-fragmentation chain-transfer (RAFT) polymerization, atom transfer radical polymerization (ATRP), electrospinning, and "click chemistry". Initially, well-defined block copolymers of 4-vinylbenzyl chloride (VBC) and glycidyl methacrylate (GMA) (PVBC-b-PGMA) were prepared via RAFT polymerization. Electrospinning of PVBC-b-PGMA from a solution in tetrahydrofuran gave rise to fibers with diameters in the range of 0.4-1.5 microm. Exposure to a solution of sodium azide (NaN(3)) not only affords nanofibers with azido groups on the surface but also leads to a cross-linking structure in the nanofibers. One more step of "click chemistry" between the PVBC-b-PGMA nanofibers with azido groups on the surface (PVBC-b-PGMA(-N3)) and alkyne-terminated polymers of N isopropylacrylamide (NIPAM) (PNIPAM(AT)), which were prepared by ATRP, allows the preparation of a PVBC-b-PGMA nanofiber with thermal-sensitive PNIPAM brushes on the surface (PVBC-b-PGMA-g-PNIPAM). PVBC-b-PGMA-g-PNIPAM nanofibers exhibit a good resistance to solvents and thermal-responsive character to the environment, having a hydrophobic surface at 45 degrees C (water contact angle approximately 140 degrees) and having a hydrophilic surface at 20 degrees C (water contact angle approximately 30 degrees). PMID- 20353209 TI - PbSe nanocrystal network formation during pyridine ligand displacement. AB - Solution-phase pyridine treatment displaced oleic acid capping ligands from the surface of PbSe nanocrystals. During ligand displacement the nanostructure morphology dramatically changed from well-stabilized, individual nanocrystals to form crystallographically connected nanocrystal networks. The network morphology was governed by the diameter of the constituent nanocrystals. Larger nanocrystals showed dipolar alignment but maintained individual nanocrystal character, while smaller nanocrystals crystallographically fused along the <100> axis. Optical studies of nanocrystal thin films showed that pyridine ligand displacement quenches the nanocrystal photoluminescence. Blends of nanocrystals and conjugated polymer showed photoluminescence quenching of the polymer with increasing nanocrystal content. The extent of photoluminescence quenching was only weakly dependent on the nanocrystal size or surface chemistry, suggesting that the interaction between nanocrystal and polymer is mostly in the form of energy transfer rather than charge transfer. PMID- 20353210 TI - 3D ordered assemblies of semiconductive micro/nanowires using microscale fibrous building blocks. AB - Three-dimensional (3D) ordered assemblies of semiconductive micro/nanowires are made by match-stick assembly of fibrous building blocks (FBBs). A glass tube filled with powders of starting material is processed drawn into centimeter-long, micrometer-diameter FBBs with controlled diameter and spacing. By repeating a draw-cut-stack process, the diameter and spacing of filling material can be programmably reduced from millimeters to hundreds of nanometers. The FBBs are densely packed into 3D ordered structures such that wires in one layer are at defined angle (theta) relative to those in the adjacent layers, where theta is between 0 and 180 degrees. The electrical measurements at bundled wires and single wire level confirm semiconducting behavior of wires. By directly manipulating microscale FBBs, the method allows high yield production of 3D ordered micro/nanowires with controlled position and orientation, enabling the construction of a new class of micro/nanomaterials. PMID- 20353211 TI - Dewetting assisted patterning of polystyrene by soft lithography to create nanotrenches for nanomaterial deposition. AB - Micromolding in capillaries of polystyrene has been carried out using a poly(dimethylsiloxane) stamp, derived from a compact disk (CD) as master, while heating above the glass transition temperature of polystyrene. The resulting pattern contained a replica of the parallel channels but with an important difference that trenches of width approximately 30 nm were found in between. The nanotrenches in polystyrene could be filled with metals by physical vapor deposition and electroless plating. This method finds potential applications in nanoelectronics and nanofluidics. PMID- 20353212 TI - Fabrication of a metal membrane on a perforated polymer substrate by palladium aerosol activation and subsequent electroless plating. AB - Fabrication of a metal membrane on a perforated flexible poly(tetrafluoroethylene) (PTFE) substrate was developed by employing spark generated palladium (Pd) aerosol activation and the subsequent electroless plating of Pd. After aerosol activation, Pd agglomerates of spark-generated primary particles (approximately 2.6 nm in diameter) with a face-centered-cubic structure were deposited uniformly on the PTFE substrate. Homogeneous Pd particles with an average size of 188 nm were tightly packed together to form a Pd membrane after Pd plating. The average plating rate of Pd during 30 min of plating at an activation intensity of 25 microg/cm(2) was 14.2 microg/cm(2) x min. PMID- 20353213 TI - Sugar-phosphole oxide conjugates as "turn-on" luminescent sensors for lectins. AB - A mixture of sugar-phosphole oxide conjugates and lectins in a buffer solution displays an intense blue emission, thereby acting as a "turn-on" fluorescent sensor for lectins as they form aggregates. PMID- 20353214 TI - Efficient near-infrared polymer and organic light-emitting diodes based on electrophosphorescence from (tetraphenyltetranaphtho[2,3]porphyrin)platinum(II). AB - The new metalloporphyrin Pt(tptnp), where tptnp = tetraphenyltetranaphtho[2,3]porphyrin, has been prepared and subjected to photophysical and electrooptical device studies. In degassed toluene solution at room temperature Pt(tptnp) features efficient phosphorescence emission with lambda(max) 883 nm with a quantum efficiency of 0.22. The complex has been used as the active phosphor in polymer and organic light-emitting diodes. Polymer light-emitting diodes based on a spin-coated emissive layer consisting of a blend of Pt(tptnp) doped in poly(9-vinylcarbazole) and 2-(4-biphenylyl)-5-(4-tert butylphenyl)-1,3,4-oxadiazole exhibit near-IR emission with lambda(max) 896 nm, with a maximum external quantum efficiency (EQE) of 0.4% and a maximum radiant emittance of 100 muW/cm(2). Organic light-emitting diodes prepared via vapor deposition of all layers and that feature an optimized multilayer hole injection and electron blocking layer heterostructure with an emissive layer consisting of 4,4'-bis(carbazol-9-yl)biphenyl (CBP) doped with Pt(tptnp) exhibit a maximum EQE of 3.8% and a maximum radiant emittance of 1.8 mW/cm(2). The polymer and organic light-emitting diodes characterized in this study exhibit record high efficiency for devices that emit in the near-IR at lambda >800 nm. PMID- 20353215 TI - Thienylsilane-modified indium tin oxide as an anodic interface in polymer/fullerene solar cells. AB - The generation and characterization of a robust thienylsilane molecular layer on indium tin oxide substrates was investigated. The molecular layer was found to reduce the oxidation potential required for the electrochemical polymerization of 3,4-ethylenedioxythiophene. The resulting electrochemically prepared poly(3,4 ethylenedioxythiophene):poly(p-styrenesulfonate) (ePEDOT:PSS) films were found to be more uniform in coverage with lower roughness and higher conductivity than analogous films fabricated with bare ITO. A relative improvement in the efficiency of 2,5-diyl-poly(3-hexylthiophene) (P3HT)/[6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) bulk heterojunction solar cells was observed when devices were formed on thienylsilane-modified ITO electrodes, rather than unmodified ITO control electrodes. PMID- 20353216 TI - Effect of the microstructure of a hyperbranched polymer and nanoclay loading on the morphology and properties of novel polyurethane nanocomposites. AB - Novel polyurethane nanocomposites based on toluene diisocyanate, poly(propylene glycol), various hyperbranched polymers (HBPs), and layered silicate were synthesized with the aim of determining the effect of the layered silicate loading and the functionality of HBP on the structure and properties of polyurethane nanocomposites. The microstructure of the nanocomposites was investigated by X-ray diffraction analysis and high-resolution transmission electron microscopy. It was found that exfoliated morphology and good dispersion were obtained up to 8 phr clay loading for all of the nanocomposites. approximately 100% increment in tensile strength, approximately 2-fold increase in the lap shear strength, approximately 200% increment in the peel strength, and 120% increment in the storage modulus along with a dramatic improvement in thermal stability were observed with the addition of 8 phr clay, over the pristine polyurethane. The higher the level of functionality of the HBP, the higher is the property enhancement. These properties were correlated with the state of dispersion of the clay platelets in the polyurethane matrix, the structure of the matrix, and clay-polymer interaction. PMID- 20353217 TI - In situ control of the oxide layer on thermally evaporated titanium and lysozyme adsorption by means of electrochemical quartz crystal microbalance with dissipation. AB - Electrochemical (EC) quartz crystal microbalance with dissipation monitoring (ECQCM-D) is a new and powerful technique for the in situ study of adsorption phenomena, e.g., as a function of the potential of the substrate. When titanium (Ti) is employed as the substrate, its oxidation behavior needs to be taken into account. Ti is always covered with a native oxide layer that can grow by, e.g., thermal oxidation or under anodic polarization. For biomolecular adsorption studies on oxidized Ti under applied potential, a stable oxide layer is desired in order to be able to distinguish the adsorption phenomena and the oxide growth. Therefore, the oxidation of thermally evaporated Ti films was investigated in phosphate-buffered saline by means of ECQCM-D, using a specially designed EC flow cell. Upon stepping the potential applied to Ti up to 2.6 V vs standard hydrogen electrode (SHE), a fast increase of the mass was observed initially for each potential step, evolving slowly to an asymptotic mass change after several hours. The oxide layer thickness increased as a quasi-linear function of the oxidation potential for potentials up to 1.8 V vs SHE. The growth rate of the oxide was around 2.5-3 nm/V. No changes in the dissipation shift were observed for potentials up to 1.8 V vs SHE. The composition of the oxide layer was analyzed by X-ray photoelectron spectroscopy (XPS). It was mainly composed of TiO(2), with a small percentage of suboxides (TiO and Ti(2)O(3)) primarily at the inner metal/oxide interface. The amount of TiO(2) increased, and that of TiO and Ti(2)O(3) decreased, with increasing oxidation potential. For each oxidation potential, the calculated thickness obtained from ECQCM-D correlated well with the thickness obtained by XPS depth profiling. A procedure to prepare Ti samples with a stable oxide layer was successfully established for investigations on the influence of an electric field on the adsorption of biomolecules. As such, the effect of an applied potential on the adsorption behavior of lysozyme on oxidized Ti was investigated. It was observed that the adsorption of lysozyme on oxidized Ti was not influenced by the applied potential. PMID- 20353218 TI - Radiation-resistant behavior of poly(vinylidene fluoride)/layered silicate nanocomposites. AB - Poly(vinylidene fluoride) (PVDF) has been made radiation-resistant through a nanocomposite (NC) route. The bombardment of high-energy swift heavy ions (SHI) on PVDF and its NCs with layered silicate has been studied in a range of fluences. The degradation of PVDF after SHI irradiation is suppressed radically in NCs. PVDF forms an intercalated nanostructure in the presence of nanoclay and, further, the ion fluence raises the extent of intercalation. The crystallinity and the heat of fusion of pristine PVDF have drastically been reduced after SHI irradiation, while there are relatively small changes in NCs even at higher fluences. The metastable piezoelectric beta form of PVDF gets stabilized by the presence of layered silicate, and the structure is retained upon SHI irradiation. The clay platelets act as nucleating agents, and SHI irradiation causes two crystallization temperatures for the samples exposed to high fluences. The damages created on the surface and bulk of PVDF and its NC films upon SHI irradiation have been measured quantitatively by using atomic force microscopy. The pitting dimensions and degradation are enhanced significantly beyond 10(11) ions/cm(2) fluence for pristine PVDF, which limits the use of PVDF for any ion irradiation application. The degradation is considerably suppressed in NCs, providing a suitable high-energy radiation-resistant thermoplastic polymer. PMID- 20353219 TI - Toward the development of partially biodegradable and injectable thermoresponsive hydrogels for potential biomedical applications. AB - A series of hydrogels containing a biodegradable dextran (Dex) chain grafted with a hydrophobic poly(-caprolactone)-2-hydroxylethyl methacrylate (PCL-HEMA) chain and a thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) chain were synthesized. The molecular weight of PCL-HEMA was determined by gel permeation chromatography, and the inner morphology of the hydrogel was observed by scanning electron microscopy. The release profiles from the hydrogels were investigated using bovine serum albumen as a model drug. It was found that the release behavior could be adjusted by varying the composition of the hydrogel. In vitro cytotoxicity studies of the hydrogels showed that the copolymer Dex-PCL HEMA/PNIPAAm exhibited low cytotoxicity. The in vivo degradation and histological studies demonstrated that the hydrogels had good biocompatibility and were promising for use as an injectable polymeric scaffold for tissue engineering applications. PMID- 20353220 TI - (Carboxymethyl)chitosan-modified superparamagnetic iron oxide nanoparticles for magnetic resonance imaging of stem cells. AB - Magnetic resonance imaging (MRI) is emerging as a powerful tool for in vivo noninvasive tracking of magnetically labeled stem cells. In this work, we present an efficient cell-labeling approach using (carboxymethyl)chitosan-modified superparamagnetic iron oxide nanoparticles (CMCS-SPIONs) as contrast agent in MRI. The CMCS-SPIONs were prepared by conjugating (carboxymethyl)chitosan to (3 aminopropyl)trimethoxysilane-treated SPIONs. These nanoparticles were internalized into human mesenchymal stem cells (hMSCs) via endocytosis as confirmed by Prussian Blue staining and electron microscopy investigation and quantified by inductively coupled plasma mass spectrometry. A MTT assay of the labeled cells showed that CMCS-SPIONs did not possess significant cytotoxicity. In addition, the osteogenic and adipogenic differentiations of the hMSCs were not influenced by the labeling process. The in vitro detection threshold of cells after incubation with 0.05 mg/mL of CMCS-SPIONs for 24 h was estimated to be about 40 cells. The results from this study indicate that the biocompatible CMCS SPIONs show promise for use with MRI in visualizing hMSCs. PMID- 20353221 TI - Fluoro-silsesquioxane-urethane hybrid for thin film applications. AB - New fluoropolyurethane hybrids containing fluorinated polyhedral oligomeric silsesquioxane were synthesized for thin film applications using fluoro(13) disilanol isobutyl-POSS (FluoroPOSS) and a short chain fluorodiol and diisocyanate. The kinetics of the urethane reaction was monitored using Fourier transform infrared spectroscopy (FTIR) and the formation of urethane was confirmed using (29)Si Nuclear magnetic resonance spectroscopy (NMR). The effect of addition of FluoroPOSS either in the I step or II step of the two step polymerization reaction is evaluated using various spectroscopic, thermal, microscopic, and diffraction techniques. In general, the major shortcoming of the lack of flexibility of fluoropolyurethane from short chain diol and diisocyanate has been overcome by the use of tethered FluoroPOSS. X-ray photoelectron spectroscopy (XPS), atomic force microscpopy (AFM), and contact angle measurements on the hybrid thin films on silicon wafer demonstrate the migration of FluoroPOSS segment to the air-thin film interface when FluoroPOSS is used in I stage reaction, and it resides at the interface when used as a chain extender. However, in both cases, the formed thin film exhibits ultrahydrophobicity with water contact angle of approximately 107 degrees and low contact angle hysteresis and solvent resistance, which are preferable for protective thin film applications. PMID- 20353222 TI - Irreversible thermochromic behavior in gold and silver nanorod/polymeric ionic liquid nanocomposite films. AB - The novel application of gold and silver nanorods as irreversible thermochromic dyes in polymeric ionic liquid (PIL) nanocomposites is proposed here. These materials have been synthesized by anion exchange of an imidazolium-based PIL in a solution that also contained gold nanorods. This resulted in the entrapment of the nanoobjects within a solid polymer precipitate. In this article, the effect of the temperature was studied in relation to the change of shape and, consequently, color of the gold or silver nanorods within the films. For the nanocomposites studied here, a maximum of two visual thermochromic transitions was observed for gold nanorods and up to three transitions were observed for silver nanorods. PMID- 20353223 TI - In situ GISAXS study of gold film growth on conducting polymer films. AB - The growth of a thin gold film on a conducting polymer surface from nucleation to formation of a continuous layer with a thickness of several nanometers is investigated in situ with grazing incidence small-angle X-ray scattering (GISAXS). Time resolution is achieved by performing the experiment in cycles of gold deposition on poly(N-vinylcarbazole) (PVK) and subsequently recording the GISAXS data. The 2D GISAXS patterns are simulated, and morphological parameters of the gold film on PVK such as the cluster size, shape, and correlation distance are extracted. For the quantitative description of the cluster size evolution, scaling laws are applied. The time evolution of the cluster morphology is explained with a growth model, suggesting a cluster growth proceeding in four steps, each dominated by a characteristic kinetic process: nucleation, lateral growth, coarsening, and vertical growth. A very limited amount of 6.5 wt % gold is observed to be incorporated inside a 1.2-nm-thick enrichment layer in the PVK film. PMID- 20353224 TI - Antibacterial properties of an in situ generated and simultaneously deposited nanocrystalline ZnO on fabrics. AB - Zinc oxide (ZnO) nanoparticles were synthesized and deposited on the surface of cotton fabrics using ultrasound irradiation. Optimization of the process resulted in a homogeneous distribution of ZnO nanocrystals, 30 nm in size, on the fabric surface. The mechanism of the ultrasound-assisted coating was proposed. The antibacterial activities of the ZnO-fabric composite were tested against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) cultures. A significant bactericidal effect, even in a 0.75% coated fabric (wt %), was demonstrated. PMID- 20353225 TI - Spatial distribution of malate dehydrogenase in chitosan scaffolds. AB - In this work, confocal laser scanning microscopy was used to study the spatial distribution of malate dehydrogenase immobilized within three-dimensional macroporous chitosan scaffolds. The scaffolds were fabricated from solutions of native and hydrophobically modified chitosan polymer through the process of thermally induced phase separation. The hydrophobically modified chitosan is proposed to possess amphiphilic micelles into which the enzyme can be encapsulated and retained. To test this theory, we applied the immobilization procedure of Klotzbach and co-workers [J. Membr. Sci. 2006, 282 (1-2), 276-283] to solutions of fluorophore-tagged malate dehydrogenase in the presence of native and hydrophobically modified chitosan polymer and then tracked the distribution of enzymes in the resulting scaffolds using fluorescent microscopy. Results suggest that the modified chitosan does encapsulate the enzyme with a significant degree of retention and with altered distribution patterns, suggesting that hydrophobic modification of the chitosan polymer backbone does create amphiphilic regions that are capable of physically encapsulating and retaining enzymes. Commentary is also given on how this information can be correlated to enzyme activity and spatial distribution during immobilization processes. PMID- 20353226 TI - In situ adhesion measurements utilizing layer-by-layer functionalized surfaces. AB - The adhesion between poly(dimethylsiloxane) (PDMS) hemispheres coated with layer by-layer (LbL) assemblies of polyelectrolytes and rigid, planar substrates was investigated using Johnson, Kendall, and Roberts (JKR) contact mechanics. Measurements were performed against amine-functionalized glass slides both in air and in aqueous solutions of controlled pH. Despite the increased density of negatively charged carboxylate groups, LbL-functionalized PDMS exhibited lower adhesion because of the combined effects of increased surface roughness and the high Young's modulus of the coating. Measurements of coated PDMS in aqueous solutions revealed tunable adhesion behavior dominated by pH-mediated changes in the mechanical properties of the coating. Smoothing the surface of the LbL coatings by aqueous salt annealing led to a significant increase in adhesion. Our results suggest that LbL assembly can be an effective means of surface functionalization for in situ adhesion measurements, but understanding and predicting the adhesion behavior requires comprehensive knowledge of the chemical, mechanical, and topological properties of the coating and how such properties change in response to the ambient environment. PMID- 20353227 TI - Variable-band-gap poly(arylene ethynylene) conjugated polyelectrolytes adsorbed on nanocrystalline TiO(2): photocurrent efficiency as a function of the band gap. AB - A series of poly(arylene ethynylene) conjugated polyelectrolytes (CPEs) substituted with carboxylic acid side groups have been synthesized and characterized. The polymers feature a backbone consisting of a carboxylated dialkoxyphenylene-1,4-ethynylene unit alternating with a second arylene ethynylene moiety of variable electron demand. The HOMO-LUMO gap is varied across the series, giving rise to a set of four polymers that have absorption maxima ranging from 404 to 495 nm. The CPEs adsorb effectively from solution onto nanostructured TiO(2) films, giving rise to TiO(2)/CPE films that absorb approximately 90% of the incident light at the absorption band maximum. The photocurrent generation efficiency of the TiO(2)/CPE films was examined in a solar cell configuration using an I(3)(-)/I(-) propylene carbonate electrolyte and a Pt/fluorine-doped tin oxide counter electrode. Most of the films exhibit good photocurrent generation efficiency with a peak quantum efficiency of approximately 50% at wavelengths corresponding to the polymers' absorption band maximum. Interestingly, the photocurrent generation efficiency for the lowest band-gap polymer is substantially lower compared to the other three systems. This effect is attributed to efficient nonradiative decay of excitons at trap sites arising from interchain contacts distal from the TiO(2)/CPE interface. PMID- 20353229 TI - Organic-inorganic hybrid compounds containing polyhedral oligomeric silsesquioxane for conservation of stone heritage. AB - Alkoxysilane solutions based on tetraethoxysilane (TEOS) have been widely used for the consolidation of decaying heritage stone surfaces. TEOS-based products polymerize within the porous structure of the decaying stone, significantly increasing the cohesion of the grains of stone components. However, they suffer from practical drawbacks, such as crack formation of the gel during the drying phase due to the developing capillary force and dense gel fractures left inside of the stone. In this study, a TEOS-based stone consolidant containing functional (3-glycidoxypropyl)trimethoxysilane (GPTMS) and polyhedral oligomeric silsesquioxane (POSS) has been prepared in order to reduce gel crack formation during the drying phase. The addition of nanometer-sized POSS and/or GPTMS having a flexible segment reduces the capillary force developed during solvent evaporation. The properties of the TEOS/GPTMS/POSS composite solutions were compared with those of commercial products (Wacker OH and Unil sandsteinfestiger OH 1:1). The gelation time was similar to that of commercial consolidants, and the TEOS/GPTMS/POSS solution was stable over a period of up to 6 months. The addition of POSS and GPTMS provided a crack-free gel, while the gel from the commercial consolidants exhibited cracks after drying. The surface hydrophobicity of the treated decayed granite increased with the addition of POSS and GPTMS, and it was higher than that of the commercial product, implying the possibility of POSS and GPTMS as barriers to the penetration of water. This result implies that the TEOS/GPTMS/POSS solution showed a high suitability for the consolidation of granite heritage. PMID- 20353228 TI - Toward understanding amino acid adsorption at metallic interfaces: a density functional theory study. AB - In examining adsorption of a few selected single amino acids on Au and Pd cluster models by density functional theory calculations, we have shown that specific side-chain binding affinity to the surface may occur because of a combination of effects, including charge transfer. Larger binding was calculated at the Pd interface. In addition, the interplay between amino acid solvation and adsorption at the interface was considered from first principles. This analysis serves as the first step toward gaining a more accurate understanding of specific interactions at the interface of biological-metal nanostructures than has been attempted in the past. PMID- 20353230 TI - Layered metal phosphonate reinforced poly(L-lactide) composites with a highly enhanced crystallization rate. AB - Layered metal phosphonate, zinc phenylphosphonate (PPZn), reinforced poly(L lactide) (PLLA) composites were fabricated by a melt-mixing technique. The nonisothermal and isothermal crystallization, melting behavior, spherulite morphology, crystalline structure, and static and dynamic mechanical properties of the PLLA/PPZn composites were investigated. PPZn shows excellent nucleating effects on PLLA crystallization. With incorporation of 0.02% PPZn, PLLA can finish crystallization under cooling at 10 degrees C/min. The crystallization rate of PLLA further increases with increasing PPZn concentration. Upon the addition of 15% PPZn, the crystallization half-times of a PLLA/PPZn composite decrease from 28.0 to 0.33 min at 130 degrees C, and from 60.2 to 1.4 min at 140 degrees C, compared to the neat PLLA. With the presence of PPZn, the nuclei number of PLLA increases and the spherulite size reduces significantly. Through analysis of the crystal structures of PLLA and PPZn, it was proposed that the nucleation mechanism of the PLLA/PPZn system is epitaxial nucleation. The incorporation of PPZn has no discernible effect on the crystalline structure of PLLA. Moreover, PPZn has good reinforcement effects on the PLLA matrix. The tensile strength of the composite is enhanced with the addition of a relatively small amount of PPZn (<5%). The tensile and storage moduli of composites increase with increasing PPZn loadings, and they respectively improve by 28% and 34% with the incorporation of a 15% PPZn filler, as compared to the neat PLLA. PMID- 20353231 TI - Tunability of mobility and conductivity over large ranges in poly(3,3''' didodecylquaterthiophene)/insulating polymer composites. AB - Semiconducting polymers are currently being considered as active layers in field effect transistors, in which high charge carrier mobility and low off conductivity are important. For other applications, such as certain spintronic mechanisms, the opposite characteristics are desirable. Blending such polymers with insulating polymers would be expected to lower the mobility. In this paper, we report that the use of hydrocarbon polymers such as polystyrene as insulators generally raises the mobility when the semiconducting polymer is poly(bisdodecylquaterthiophene). A high mobility value of nearly 0.1 cm(2)/V.s was obtained for an optimal blend. While this is counterintuitive, it is consistent with a few other recent reports. In order to lower the mobility significantly, a much more polar and irregular blending agent is needed. The further addition of tetrafluorotetracyanoquinodimethane as a dopant gave a rare low mobility/high conductivity combination of properties, with a charge carrier density on the order of 10(19) cm(-3). Thus, mobility and conductivity were tuned somewhat independently over 3 and 4 orders of magnitude, respectively. PMID- 20353232 TI - Miniature boats with striking loading capacity fabricated from superhydrophobic copper meshes. AB - A novel kind of miniature boat that might have many potential applications was fabricated from superhydrophobic copper meshes for the first time. These boats not only floated freely on a water surface but also exhibited striking loading capacities. By selection of the pore size of copper meshes, a loading capacity greater than 11.0 g could be readily achieved for a boat of 8.0 cm(3) in volume. The large loading capacity is believed to arise from the air film surrounding the superhydrophobic surfaces of boats. The results of this study present new applications of artificial superhydrophobic surfaces in areas of miniature aquatic devices. PMID- 20353233 TI - Reactivity of nanostructured MnO(2) in alkaline medium studied with a micro cavity electrode: effect of synthesizing temperature. AB - The influence of synthesizing temperature of manganese dioxide (MnO(2)) powders on their electrochemical reactivity in 1 M KOH was investigated. These powders were prepared chemically by the hydrothermal method by oxidation of Mn(2+) by ammonium peroxodisulphate. The observations by scanning electronic microscopy, energy-dispersive X-ray analyses, and transmission electron microscopy techniques on MnO(2) obtained at different temperatures show the formation of many nanometre scale sticks lumped together to form a spherical particle of several micrometers. The results obtained by BET and BJH methods reveal mesoporous texture, and the MnO(2) synthesized at 90 degrees C presents the largest expanded surface area. The electrochemical reactivity of these powders in 1 M KOH was characterized with microcavity electrode by cyclic voltammetry and electrochemical impedance spectroscopy. The results illustrate that the nanostructured MnO(2) powder synthesized at 90 degrees C shows the highest electrochemical reactivity in agreement with BET data. The X-ray powder diffraction identified the gamma MnO(2), known as the most reactive species. PMID- 20353234 TI - Blue to true-blue phosphorescent Ir(III) complexes bearing a nonconjugated ancillary phosphine chelate: strategic synthesis, photophysics, and device integration. AB - We report the design and synthesis of Ir(III) complexes functionalized with substituted pyridyl cyclometalate or azolate chromophores, plus one newly designed nonconjugated phosphine chelate, which not only greatly restricts its participation in the lowest-lying electronic transition but also enhances the coordination strength. These two key factors lead to fine-tuning of the phosphorescence chromaticity toward authentic blue and simultaneously suppress, in part, the nonradiative deactivation. This conceptual design presents a novel strategy in achieving heretofore uncommon, high-efficiency blue and true-blue phosphorescence. The fabrication of the organic light-emitting devices (OLEDs) employing phosphorescent dopants [Ir(dfpbpy)(2)(P(wedge)N)] (1b) and [Ir(fppz)(2)(P(wedge)N)] (3) was successfully made, for which the abbreviations (dfpbpy)H, (fppz)H, and (P(wedge)N)H represent 2-(4,6-difluorophenyl)-4-tert butylpyridine, 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole, and 5 (diphenylphosphinomethyl)-3-(trifluoromethyl)pyrazole, respectively. Of particular interest is the 3-doped OLEDs, which exhibit remarkable maximum efficiencies of 6.9%, 8.1 cd A(-1), and 4.9 lm W(-1), together with a true-blue chromaticity CIE(x,y) = 0.163, with 0.145 recorded at 100 cd m(-2). PMID- 20353235 TI - Anomalous tunneling in carbon/alkane/TiO(2)/gold molecular electronic junctions: energy level alignment at the metal/semiconductor interface. AB - Carbon/TiO(2)/gold electronic junctions show slightly asymmetric electronic behavior, with higher current observed in current density (J)/voltage (V) curves when carbon is biased negative with respect to the gold top contact. When a approximately 1-nm-thick alkane film is deposited between the carbon and TiO(2), resulting in a carbon/alkane/TiO(2)/gold junction, the current increases significantly for negative bias and decreases for positive bias, thus creating a much less symmetric J/V response. Similar results were obtained when SiO(2) was substituted for the alkane layer, but Al(2)O(3) did not produce the effect. The observation that, by the addition of an insulating material between carbon and TiO(2), the junction becomes more conductive is unexpected and counterintuitive. Kelvin probe measurements revealed that while the apparent work function of the pyrolyzed photoresist film electrode is modulated by surface dipoles of different surface-bound molecular layers, the anomalous effect is independent of the direction of the surface dipole. We propose that by using a nanometer-thick film with a low dielectric constant as an insertion layer, most of the applied potential is dropped across this thin film, thus permitting alignment between the carbon Fermi level and the TiO(2) conduction band. Provided that the alkane layer is sufficiently thin, electrons can directly tunnel from carbon to the TiO(2) conduction band. Therefore, the electron injection barrier at the carbon/TiO(2) interface is effectively reduced by this energy-level alignment, resulting in an increased current when carbon is biased negative. The modulation of injection barriers by a low-kappa molecular layer should be generally applicable to a variety of materials used in micro- and nanoelectronic fabrication. PMID- 20353236 TI - Effects of reactive compatibilization on the morphological, thermal, mechanical, and rheological properties of intumescent flame-retardant polypropylene. AB - Flame-retardant polypropylene (PP) samples were in situ compatibilized with maleic anhydride grafted PP. Compatibilization reaction was verified by an IR spectrum and gel content measurements. Electron microscopy images showed that compatibilization could considerably reduce the size of the flame-retardant domains, control the phase morphology, and improve the interfacial adhesion between PP and intumescent flame retardant (IFR) with different IFR loading levels. The limiting oxygen index (LOI) of flame-retardant PP increased to different extents after compatibilization, indicating an improvement in the flame retardancy. Compatibilization enhanced the thermal stability to some extent and remarkably delayed thermal oxidative degradation of flame-retardant PP. For PP containing 20 wt % flame retardant, the temperature at which the maximum weight loss rate occurred was enhanced by about 99 degrees C after compatibilization. The storage modulus and glass transition temperatures were elevated to different extents. Tensile strengths of samples reduced in the presence of flame retardant alone but in the additional presence of compatibilizer were restored to levels similar to those of pure PP. Elongation-at-break values, however, showed IFR concentration-dependent reductions that were less for compatibilized samples. Furthermore, the complex viscosity of a compatibilized PP melt turned slightly smaller, which is favorable to melt processing. PMID- 20353237 TI - Selective synthesis of manganese oxide nanostructures for electrocatalytic oxygen reduction. AB - This work presents two points with respect to manganese oxide (MnO(x)) nanomaterials: their controllable synthesis with desired phases and shapes together with their applications as catalysts for oxygen reduction and Al/air batteries. Solid MnO(x) with crystalline phases of MnOOH, Mn(2)O(3), and MnO(2) as well as shapes of the sphere, wire, rod, and particle were prepared through a simple one-pot hydrothermal route. Selective preparation was achieved by adjusting the surfactant concentration that controls simultaneously the growth thermodynamic and dynamic parameters of MnO(x) nanocrystals. Electrochemical investigations show that the obtained Mn(2)O(3) nanowires, which possess a large aspect ratio and preferentially exposed (222) crystal surfaces, exhibit remarkable catalytic activity (comparable to Pt/C counterparts) toward the electroreduction of oxygen in alkaline media. The tailored MnO(x) nanostructures may find prospective applications as low-cost catalysts for alkaline fuel cells and metal/air batteries. PMID- 20353238 TI - Bisimidazolium ionic liquids as the high-performance antiwear additives in poly(ethylene glycol) for steel-steel contacts. AB - Bisimidazolium ionic liquids [C(10)(m(2)im)(2)(NTf(2))(2), C(10)(m(2)im)(2)(PF(6))(2), and C(10)(m(2)im)(2)(BF(4))(2)] with different anions were evaluated as the antiwear additives in poly(ethylene glycol) at room temperature. Results showed that they could effectively reduce the friction and wear of sliding pairs compared with the cases without these additives. Especially, C(10)(m(2)im)(2)(NTf(2))(2) showed better antiwear properties with an optimum concentration of 3 wt %, by which a significant improvement of its antiwear property by dozens of times with respect to the base oil was achieved. The excellent tribological properties are attributed to the formation of high quality physical adsorption films and tribochemical product during friction and the good miscibility of ionic liquids with base oil. PMID- 20353239 TI - Diffusion and flow across nanoporous polydicyclopentadiene-based membranes. AB - We report gas and liquid transport measurements through membranes that have 40% voids made of 14 nm pores. A reactive polylactide-polynorbornenylethylstyrene block polymer is used as a structural template in the polymerization of dicyclopentadiene during the membrane formation process. After the membrane is cast, the pore structure is formed by etching the polylactide component using dilute aqueous base. The pore structure is isotropic; therefore, there is no need for special alignment techniques. Knudsen diffusion experiments and water flow experiments show pores with a tortuosity of 1.81 and a size of 14 nm, a diameter consistent with nitrogen adsorption and small-angle X-ray scattering measurements. These membranes are effective for ultrafiltration, with molecular weight cutoffs (MWCO) consistent with theoretical predictions with no adjustable parameters. These MWCO's can be tuned by changing the size of the constituent blocks in the templating copolymer. PMID- 20353240 TI - Improved cleaning of hydrophilic protein-coated surfaces using the combination of Nanobubbles and SDS. AB - The use of nanobubbles, the common surfactant sodium dodecyl sulfate (SDS), and nanobubbles in combination with SDS as cleaning agents to remove lysozyme from the solid-liquid interface has been investigated using a quartz crystal microbalance on both hydrophobic and hydrophilic surfaces. On the hydrophobic surface, significant amounts of protein remained on the surface after 10 cycles of nanobubble treatment for 10 s periods in phosphate buffer. The cleaning efficiency of SDS was far superior and was shown to remove approximately 90% of the protein. The use of nanobubbles in combination with SDS failed to improve the cleaning efficiency further. On the other hand, lysozyme on the hydrophilic surface cannot be removed effectively by either 10 cycles of cleaning with nanobubbles or 10 cycles of cleaning with SDS. Nevertheless, the protein can be removed completely after 6 cycles of cleaning with nanobubbles in combination with SDS. PMID- 20353241 TI - Formation of close-packed nanoparticle chains. AB - The self-assembly of CoPt(3) particles (diameter 6 nm) into low-dimensional ordered arrays results from phase separation in a hexane solution containing nanoparticles, hexadecylamine, and water. The evaporation of hexane from the thin film of solution initiates the formation of a water layer on the solid substrate. Subsequent dewetting of this water layer leads to the formation of water droplets. The nanoparticles follow the motion of the contact line of the dewetting water layer and thus assemble into ordered arrays at the periphery of the water droplets. PMID- 20353242 TI - Polymeric N-halamine latex emulsions for use in antimicrobial paints. AB - A new N-halamine monomer, N-chloro-2,2,6,6-tetramethyl-4-piperidinyl methacrylate (Cl-TMPM), was synthesized and used to prepare water-based polymeric N-halamines by emulsion polymerization. The chemical structures of the samples were characterized with Fourier transform IR, (13)C NMR, UV/vis, and differential scanning calorimetry analyses. Upon the addition of a small amount of the polymeric N-halamine latex emulsions into commercial water-based latex paints as antimicrobial additives, the new paints provided potent antimicrobial activities against Staphylococcus aureus (S. aureus; Gram-positive bacteria), methicillin resistant S. aureus (MRSA; drug-resistant Gram-positive bacteria), vancomycin resistant enterococcus (VRE; drug-resistant Gram-positive bacteria), Escherichia coli (E. coli; Gram-negative bacteria), Candida tropicalis (C. tropicalis; fungi), MS2 virus (15597-B; virus), and Stachybotrys chartarum spore (S. chartarum; mold), and they successfully prevented biofilm formation and development. The antimicrobial functions of the new paints were long-lasting for more than 1 year under normal in-use conditions, easily monitorable by a simple potassium iodine/starch test, and readily rechargeable if the functions were accidentally lost as a result of challenging conditions such as heavy soil, flooding, etc. PMID- 20353243 TI - Structural characterization and biological fluid interaction of Sol-Gel-derived Mg-substituted biphasic calcium phosphate ceramics. AB - Sol-Gel chemistry has been used to prepare undoped and Mg-substituted biphasic calcium phosphate (BCP) ceramics composed of hydroxyapatite (HAp) and whitlockite (beta-TCP) phases. Different series of samples have been synthesized with different Mg-doping levels (from 0 to 5 atomic % of Ca atoms substituted) and different temperatures of calcination (from 500 to 1100 degrees C). All of the powdered samples were systematically treated by Rietveld refinement to extract the quantitative phase analysis and the structural and microstructural parameters, to locate the Mg crystallographic sites, and to refine the composition of the Mg-substituted phases. The temperature dependence of the weight amount ratio between HAp and beta-TCP is not monotonic because of the formation of minor phases such as Ca(2)P(2)O(7), CaO, MgO, and CaCO(3) and certainly an amorphous phase. On the other hand, the Mg stabilizing feature on the beta-TCP phase has been evidenced and explained. The mechanism of stabilization by small Mg(2+) is different from that by large Sr(2+). Nevertheless, in both cases, the beta-TCP stabilization is realized by an improvement of the environment of the Ca4 site unusually face-coordinated to a PO(4) tetrahedron. The substitution of a Mg atom in the Ca5 site allows considerable improvement of the bond valence sum of the unusual Ca4 polyhedron. The temperatures of calcination combined with the amount of Mg atoms introduced allow monitoring of the phase composition of the BCP ceramics as well as their microstructural properties. The bioactivity properties of the BCP samples are improved by the presence of Mg atoms in the structure of the beta-TCP phase. The mechanism of improvement is mainly attributed to an accelerated kinetic of precipitation of a calcium phosphate layer at the surface comprising HAp and/or beta-TCP phases. PMID- 20353244 TI - A highly selective, biofunctional surface for molecule/cell sorting. AB - We report in this paper an approach to the effective capture of IgM antibodies from antisera and solutions based on the formation of a carpet of molecules exposing thiols off a surface. Surfaces of different nature, such as OH-exposing (glass, SiO(2), metal oxides, etc.) and noble metal ones (Au, Ag, etc.), have been first functionalized in the liquid phase by suitable chemistry [3 (mercaptopropyl)trimethoxysilane or 1,4-benzenedimethanethiol]. The resulting exposed SH moieties have been further used for binding anti-A, -B, and -D IgM molecules from goat sera via a thiol exchange reaction involving the J chain and other disulfide bonds present in the IgM molecular structure. Antibodies preserve their functional activity at the surface and appear to be able to bind specifically erythrocytes of the proper group in a fast and reliable way. These results can be generalized to the use of any kind of IgM antibody and can be valuable in surface biofunctionalization in the fields of biosensors and immunoassays. PMID- 20353245 TI - Poly(ethylene imine) and tetraethylenepentamine as protecting agents for metallic copper nanoparticles. AB - The aim of this research was to explore the use of amine-containing polymeric and low-molar-mass organic protecting agents in the preparation of copper nanoparticles. Particles were synthesized using poly(ethylene imine) (PEI) or tetraethylenepentamine (TEPA) as protecting agents. The resulting particles were studied with UV-vis spectrometry, thermogravimetry, scanning electron microscopy, and transmission electron microscopy, wide-angle X-ray scattering with heating, X ray photoelectron spectroscopy, and Auger electron spectroscopy. The average crystal sizes for the particles were at room temperature 8.5 and 19.4 nm for PEI and TEPA, respectively, and some surface oxidation was observed. The particles were sintered on paper, and the resistance and resistivity were measured. For Cu/PEI samples, the protecting agent was removed upon sintering at relatively low temperatures (between 150 and 200 degrees C). At this temperature range, particles exhibited a rapid increase in the crystal size. Sintered particles exhibited high conductivity, indicating that these kinds of materials might find use in paper-based printing. PMID- 20353246 TI - Coarse-grained molecular dynamics study of permeability enhancement in DPPC bilayers by incorporation of lysolipid. AB - The enhanced permeability of flat lipid bilayer membranes at their gel to liquid crystalline (LC) phase transition has been explored using coarse-grained molecular dynamics. The phase transition temperature, T(m), is deduced by monitoring the area per lipid, the lipid lateral diffusion constant, and the lipid-lipid radial distribution function. We find that a peak in the permeability coincides with the phase transition from the gel to LC state when lysolipid is present. This peak in permeability correlates with a jump in the area per lipid near the same temperature as well as increased fluctuations in the lipid bilayer free volume. At temperatures above T(m), the permeability is only slightly dependent on the amount of lysolipid present. The increased free volume due to the "missing tail" of the lysolipid is partially compensated for by a decrease in area per lipid as the amount of lysolipid increases. We also found that in the coarse-grained model a small amount (< or = 15 mol %) of lysolipid stabilizes the gel phase and increases the phase transition temperature, while a larger amount of lysolipid (20 mol %) reduces T(m) back to that for pure DPPC, and bilayers consisting of > or = 30 mol % lysolipid did not form a gel phase but still exhibited a peak in permeability near T(m) for pure DPPC. PMID- 20353247 TI - Minimal size of coffee ring structure. AB - A macroscopic evaporating water droplet with suspended particles on a solid surface will form a ring-like structure at the pinned contact line due to induced capillary flow. As the droplet size shrinks, the competition between the time scales of the liquid evaporation and the particle movement may influence the resulting ring formation. When the liquid evaporates much faster than the particle movement, coffee ring formation may cease. Here, we experimentally show that there exists a lower limit of droplet size, D(c), for the successful formation of a coffee ring structure. When the particle concentration is above a threshold value, D(c) can be estimated by considering the collective effects of the liquid evaporation and the particle diffusive motion within the droplet. For suspended particles of size approximately 100 nm, the minimum diameter of the coffee ring structure is found to be approximately 10 microm. PMID- 20353248 TI - NMR and quantum chemistry study of mesoscopic effects in ionic liquids. AB - (1)H, (13)C, and (81)Br NMR spectra of the neat room-temperature ionic liquid (RTIL), namely, 1-decyl-3-methyl-imidazolium bromide ([C(10)mim][Br]) as well as its solutions in acetonitrile, dichloromethane, methanol, and water have been investigated. The most important observation of the present work is the significant broadening of (81)Br NMR signal in the solutions of [C(10)mim][Br] in organic solvents, which molecules tend to associate into hydrogen bond networks and the appearance of the complex contour of (81)Br NMR signal in the neat RTIL as well as in the liquid crystalline (LC) ionogel formed in RTIL/water solution. The complex structure of (81)Br signal changes upon heating and dilution in water. It disappears at ca. 353 K and in the aqueous solution below ca. 0.1 mol fraction of RTIL. Several new (1)H NMR signals appear at the [C(10)mim][Br]/water compositions just before the solidification of the sample (approximately 0.3 mol fraction of [C(10)mim][Br]). These additional peaks can be attributed to the H(2)O protons placed in inhomogeneous regions of the sample or due to the appearance of nonequivalent water sites in LC ionogel, the exchange between which is highly restricted or even frozen. The complex shape of (81)Br NMR signal can originate from the presence of supra-molecular structures (mesoscopic domains) that live over the period of the NMR time-scale due to a very high viscosity of [C(10)mim][Br]. These domains exhibit some features of partially disordered solids (liquid- or plastic crystals). To evaluate the static and dynamic contributions into the relaxation rate of (81)Br nuclei, the quantum chemistry calculations of the electronic structure, magnetic shielding, and electric field gradient (EFG) tensors of [C(10)mim][Br] and related model systems (Br(-).6H(2)O cluster, with addition of the dipoles (hydrogen fluoride) and charged particles - cations: H(+) or C(1)mim(+)) were performed. PMID- 20353249 TI - In situ crystallization of low-melting ionic liquid [BMIM][PF6] under high pressure up to 2 GPa. AB - To develop a new practical method of purifying and recycling ionic liquids, we performed direct microscopic observations and in situ crystallization of low melting ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]), in detail by high pressure Raman spectroscopy. Compression of [BMIM][PF(6)] was measured under pressures up to about 2.0 GPa at temperatures 293-353 K by using a high pressure diamond anvil cell (DAC). At room temperature, with pressure increasing, the characteristic bands of [BMIM][PF(6)] displayed nonmonotonic pressure-induced frequency shifts, and [BMIM][PF(6)] experienced the liquid-solid phase transition at about 0.50 GPa. In separate experiments, in situ crystallization of low-melting ionic liquid [BMIM][PF(6)] were also measured at various P-T regions, in order to improve the understanding of its stability limits. Finally, the T versus P phase diagram of [BMIM][PF(6)] was constructed, and it showed that the melting point was an increase function of pressure. It was also indicated that the structure changes in the crystalline and liquid states under high pressure might also be associated with conformational changes in the butyl chain. Pressure-released Raman spectra also showed that the phase transition of [BMIM][PF(6)] was reversible. PMID- 20353250 TI - Molecular dynamics study of alkyl benzene sulfonate at air/water interface: effect of inorganic salts. AB - Molecular dynamics simulations have been performed to investigate the effect of inorganic salts on the structural and dynamic properties of alkyl benzene sulfonate monolayer formed at the air/water interface. The alkyl benzene sulfonates are two surfactant isomers in the family of sodium hexadecane benzene sulfonates defined by 1C16 and 5C16, indicating a benzene sulfonate group attached to the first and fifth carbon atom in hexadecane backbone. It has been observed that both benzene ring groups and headgroups (-SO(3)(-)) are hydrated due to their polar nature. Water molecules can form stable hydrogen bonds with headgroups of surfactants, and the counterions (Na(+), Mg(2+), or Ca(2+)) are distributed close to the air/water interface. The stronger electrostatic repulsion drives the 1C16 monolayer arranged in disorder in comparison with 5C16, and the presence of inorganic salts may screen electrostatic repulsions between headgroups and decrease the thickness of the interfacial water layer, which follows the series Ca(2+) > Mg(2+) > Na(+). The order of inorganic salt tolerance of two surfactants is 5C16 > 1C16. The counterions may penetrate into the hydration shell of the surfactant headgroups and restrict the mobility of the water molecules situated in this area. PMID- 20353251 TI - Raman characterization of monolayers formed from mixtures of sodium 2 mercaptoethanesulfonate and various aromatic mercapto-derivative bases. AB - Metal electrodes covered with organic (mono)layers containing pi-delocalized structures have many potential applications, for example, in construction of bioelectronic elements with high efficiency of electron transfer. In this contribution, a silver surface was modified with mixed monolayers formed from sodium 2-mercaptoethanesulfonate (MES) and four model (stable and easily available) aromatic thiols with strong basic properties: 4,6-diamino-2 mercaptopyrimidine (APY), 1H-1,2,4-triazole-3-thiol (HTR), 4-methyl-1,2,4 triazole-3-thiol (MTR), and 3-amino-1,2,4-triazole-5-thiol (ATR). The structure of the formed monolayers was determined from surface-enhanced Raman scattering (SERS) measurements. These studies showed that, despite significant differences in the molecular structures, MES is a very promising candidate for making mixed monolayers with mercapto-derivative aromatic bases that are relatively homogeneous (without large one-component domains) in broad pH range. At high pH, in a one-component ATR monolayer, a significant amount of molecules are in the anionic form and adopt a flat orientation versus the metal surface. At the same pH, in mixed ATR+MES monolayers, a significantly larger part of ATR molecules than for the respective one-component monolayer is adsorbed in the neutral form with the aromatic ring(s) oriented perpendicularly to the metal surface. Also in the mixed APY+MES and HTR+MES monolayers, a significantly smaller part of HTR or APY molecules than for the respective one-component HTR and APY monolayers is deprotonated. The structure of the MTR monolayer practically does not depend on the pH of the surrounding solution. Increase of the ratio of acidic dissociation and reorientation of ATR molecules from the perpendicular to the parallel orientation is also observed during storage of the respective one-component and mixed monolayers in water, phosphorus buffers, and in the solutions of model peptides (bovine serum albumin or laccase). In some cases, the reorientation of ATR molecules forming the linkage monolayer when immersed in the peptide solution is very large. Significant spectral changes during soaking in water and solutions of model peptides has also been observed for APY monolayers. All studied mixed monolayers practically prevent the direct adsorption of peptides on the metal surface for at least 30 min. PMID- 20353252 TI - Charge transport in DNA oligonucleotides with various base-pairing patterns. AB - We combined various experimental (scanning tunneling microscopy and Raman spectroscopy) and theoretical (density functional theory and molecular dynamics) approaches to study the relationships between the base-pairing patterns and the charge transfer properties in DNA 32-mer duplexes that may be relevant for identification and repair of defects in base pairing of the genetic DNA and for DNA use in nanotechnologies. Studied were two fully Watson-Crick (W-C)-paired duplexes, one mismatched (containing three non-W-C pairs), and three with base pairs chemically removed. The results show that the charge transport varies strongly between these duplexes. The conductivity of the mismatched duplex is considerably lower than that of the W-C-paired one despite the fact that their structural integrities and thermal stabilities are comparable. Structurally and thermally much less stable abasic duplexes have still lower conductivity but not markedly different from the mismatched duplex. All duplexes are likely to conduct by the hole mechanism, and water orbitals increase the charge transport probability. PMID- 20353253 TI - Bioprinting endothelial cells with alginate for 3D tissue constructs. AB - Advanced solid freeform fabrication (SFF) techniques have been an interest for constructing tissue engineered polymeric scaffolds because of its repeatability and capability of high accuracy in fabrication resolution at the scaffold macro- and microscales. Among many important scaffold applications, hydrogel scaffolds have been utilized in tissue engineering as a technique to confide the desired proliferation of seeded cells in vitro and in vivo into its architecturally porous three-dimensional structures. Such fabrication techniques not only enable the reconstruction of scaffolds with accurate anatomical architectures but also enable the ability to incorporate bioactive species such as growth factors, proteins, and living cells. This paper presents a bioprinting system designed for the freeform fabrication of porous alginate scaffolds with encapsulated endothelial cells. The bioprinting fabrication system includes a multinozzle deposition system that utilizes SFF techniques and a computer-aided modeling system capable of creating heterogeneous tissue scaffolds. The manufacturing process is biologically compatible and is capable of functioning at room temperature and relatively low pressures to reduce the fluidic shear forces that could deteriorate biologically active species. The deposition system resolution is 10 microm in the three orthogonal directions XYZ and has minimum velocity of 100 microm/s. The ideal concentrations of sodium alginate and calcium chloride were investigated to determine a viable bioprinting process. The results indicated that the suitable fabrication parameters were 1.5% (w/v) sodium alginate and 0.5% (w/v) calcium chloride. Degradation studies via mechanical testing showed a decrease in the elastic modulus by 35% after 3 weeks. Cell viability studies were conducted on the cell encapsulated scaffolds for validating the bioprinting process and determining cell viability of 83%. This work exhibits the potential use of accurate cell placement for engineering complex tissue regeneration using computer-aided design systems. PMID- 20353254 TI - The role of cortical shell and trabecular fabric in finite element analysis of the human vertebral body. AB - Classical finite element (FE) models can estimate vertebral stiffness and strength with much lower computational costs than muFE analyses, but the accuracy of these models rely on calibrated material properties that are not necessarily consistent with experimental results. In general, trabecular bone material properties are scaled with computer tomography (CT) density alone, without accounting for local variations in anisotropy or micro-architecture. Moreover, the cortex is often omitted or assigned with a constant thickness. In this work, voxel FE models, as well as surface-based homogenized FE models with topologically-conformed geometry and assigned with experimentally validated properties for bone, were developed from a series of 12 specimens tested up to failure. The effects of changing from a digital mesh to a smooth mesh, including a cortex of variable thickness and/or including heterogeneous trabecular fabric, were investigated. In each case, FE predictions of vertebral stiffness and strength were compared with the experimental gold-standard, and changes in elastic strain energy density and damage distributions were reported. The results showed that a smooth mesh effectively removed zones of artificial damage locations occurring in the ragged edges of the digital mesh. Adding an explicit cortex stiffened and strengthened the models, unloading the trabecular centrum while increasing the correlations to experimental stiffness and strength. Further addition of heterogeneous fabric improved the correlations to stiffness (R(2)=0.72) and strength (R(2)=0.89) and moved the damage locations closer to the vertebral endplates, following the local trabecular orientations. It was furthermore demonstrated that predictions of vertebral stiffness and strength of homogenized FE models with topologically-conformed cortical shell and heterogeneous trabecular fabric correlated well with experimental measurements, after assigning purely experimental data for bone without further calibration of material laws at the macroscale of bone. This study successfully demonstrated the limitations of current classical FE methods and provided valuable insights into the damage mechanisms of vertebral bodies. PMID- 20353255 TI - A two-dimensional computational model of lymph transport across primary lymphatic valves. AB - This study utilizes a finite element model to characterize the transendothelial transport through overlapping endothelial cells in primary lymphatics during the uptake of interstitial fluid. The computational model is built upon the analytical model of these junctions created by Mendoza and Schmid-Schonbein (2003, "A Model for Mechanics of Primary Lymphatic Valves," J. Biomed. Eng., 125, pp. 407-414). The goal of the present study is to investigate how adding more sophisticated and physiologically representative biomechanics affects the model's prediction of fluid uptake. These changes include incorporating a porous domain to represent interstitial space, accounting for finite deformation of the deflecting endothelial cell, and utilizing an arbitrary Lagrangian-Eulerian algorithm to account for interacting and nonlinear mechanics of the junctions. First, the present model is compared with the analytical model in order to understand its effects on parameters such as cell deflection, pressure distribution, and velocity profile of the fluid entering the lumen. Without accounting for the porous nature of the interstitium, the computational model predicts greater cell deflection and consequently higher lymph velocities and flow rates than the analytical model. However, incorporating the porous domain attenuates the cell deflection and flow rate to values below that predicted by the analytical model for a given transmural pressure. Second, the present model incorporates recent experimental data for parameters such as lymph viscosity, transmural pressure measurements, and others to evaluate the ability of these junctions to act as unidirectional valves. The volume of flow through the valve is calculated to be 0.114 nL/microm per cycle for a transmural pressure varying between 8.0 mm Hg and -1.0 mm Hg at 0.4 Hz. Though experimental data for the absorption of lymph through these endothelial junctions are scarce, several measurements of lymph velocity and flow rates are cited to validate the present model. PMID- 20353256 TI - Numerical study of blood flow at the end-to-side anastomosis of a left ventricular assist device for adult patients. AB - We use an implicit large eddy simulation (ILES) method based on a finite volume approach to capture the turbulence in the anastomoses of a left ventricular assist device (LVAD) to the aorta. The order-of-accuracy of the numerical schemes is computed using a two-dimensional decaying Taylor-Green vortex. The ILES method is carefully validated by comparing to documented results for a fully developed turbulent channel flow at Re(tau)=395. Two different anastomotic flows (proximal and distal) are simulated for 50% and 100% LVAD supports and the results are compared with a healthy aortic flow. All the analyses are based on a planar aortic model under steady inflow conditions for simplification. Our results reveal that the outflow cannulae induce high exit jet flows in the aorta, resulting in turbulent flow. The distal configuration causes more turbulence in the aorta than the proximal configuration. The turbulence, however, may not cause any hemolysis due to low Reynolds stresses and relatively large Kolmogorov length scales compared with red blood cells. The LVAD support causes an acute increase in flow splitting in the major branch vessels for both anastomotic configurations, although its long-term effect on the flow splitting remains unknown. A large increase in wall shear stress is found near the cannulation sites during the LVAD support. This work builds a foundation for more physiologically realistic simulations under pulsatile flow conditions. PMID- 20353257 TI - Age dependent mechanical properties of the infant porcine parietal bone and a correlation to the human. AB - An infant less than 18 months of age with a skull fracture has a one in three chance of abuse. Injury biomechanics are often used in the investigation of these cases. In addition to case-based investigations, computer modeling, and test dummies, animal model studies can aid in these investigations. This study documents age effects on the mechanical properties of parietal bone and coronal suture in porcine infants and correlates the bending properties of the bone to existing human infant data. Three beam specimens were cut from porcine specimens aged 3 days, 7 days, 10 days, 14 days, 18 days, and 21 days: one across the coronal suture and two from the parietal bone, one parallel to and one perpendicular to the coronal suture. An actuator-mounted probe applied four-point bending in displacement control at 25 mm/s until failure. Bending stiffness of bone specimens increased with age; bone-suture-bone specimens showed no change up to 14 days but increased from 14 days to 18 days. All three specimen types showed decreases in ultimate stress with age. Ultimate strain for the bone-suture-bone specimens was significantly higher than that for the bone specimens up to 14 days with no differences thereafter. There was no change in the bending modulus with age for any specimen type. Bone-suture-bone bending modulus was lower than that of the bone specimens up to 14 days with no differences thereafter. There was no change in strain energy to failure with age for the bone specimens; bone-suture bone specimens showed no change up to 14 days but decreased from 14 days to 18 days. There was an increase in specimen porosity with age. Correlation analysis revealed a weak (-0.39) but significant and negative correlation between ultimate stress and porosity. While the mechanical properties of parietal bone and coronal suture did not change significantly with age, bone specimens showed an increase in bending stiffness with age. Bone-suture-bone specimens showed an increase in bending stiffness only between 14 days and 18 days of age. Correlation analyses using existing and new data to compute the bending rigidity of infant parietal bone specimens suggested that days of pig age may correlate with months of human age during the most common time frame of childhood abuse cases. PMID- 20353258 TI - Theoretical and uniaxial experimental evaluation of human annulus fibrosus degeneration. AB - The highly organized structure and composition of the annulus fibrosus provides the tissue with mechanical behaviors that include anisotropy and nonlinearity. Mathematical models are necessary to interpret and elucidate the meaning of directly measured mechanical properties and to understand the structure-function relationships of the tissue components, namely, the fibers and extrafibrillar matrix. This study models the annulus fibrosus as a combination of strain energy functions describing the fibers, matrix, and their interactions. The objective was to quantify the behavior of both nondegenerate and degenerate annulus fibrosus tissue using uniaxial tensile experimental data. Mechanical testing was performed with samples oriented along the circumferential, axial, and radial directions. For samples oriented along the radial direction, the toe-region modulus was 2x stiffer with degeneration. However, no other differences in measured mechanical properties were observed with degeneration. The constitutive model fit well to samples oriented along the radial and circumferential directions (R(2)> or =0.97). The fibers supported the highest proportion of stress for circumferential loading at 60%. There was a 70% decrease in the matrix contribution to stress from the toe-region to the linear-region of both the nondegenerate and degenerate tissue. The shear fiber-matrix interaction (FMI) contribution increased by 80% with degeneration in the linear-region. Samples oriented along the radial and axial direction behaved similarly under uniaxial tension (modulus=0.32 MPa versus 0.37 MPa), suggesting that uniaxial testing in the axial direction is not appropriate for quantifying the mechanics of a fiber reinforcement in the annulus. In conclusion, the structurally motivated nonlinear anisotropic hyperelastic constitutive model helps to further understand the effect of microstructural changes with degeneration, suggesting that remodeling in the subcomponents (i.e., the collagen fiber, matrix and FMI) may minimize the overall effects on mechanical function of the bulk material with degeneration. PMID- 20353259 TI - Recruitment viscoelasticity of the tendon. AB - There is still no agreement on the nature of tissues' viscoelasticity and on its reliable modeling. We speculate that disagreements between previous observations stem from difficulties of separating between viscoelastic and preconditioning effects, since both are manifested by similar response features. Here, this and related issues were studied in the tendon as a prototype for other soft tissues. Sheep digital tendons were preconditioned under strain that was higher by 1% than the one used in subsequent testing. Each specimen was then subjected to stress relaxation, and quick release or creep. A stochastic microstructural viscoelastic theory was developed based on the collagen fibers' properties and on their gradual recruitment with stretch. Model parameters were estimated from stress relaxation data and predictions were compared with the creep data. Following its validation, the new recruitment viscoelasticity (RVE) model was compared, both theoretically and experimentally, with the quasilinear viscoelastic (QLV) theory. The applied preconditioning protocol produced subsequent pure viscoelastic response. The proposed RVE model provided excellent fit to both stress relaxation and creep data. Both analytical and numerical comparisons showed that the new RVE theory and the popular QLV one are equivalent under deformation schemes at which no fibers buckle. Otherwise, the equivalence breaks down; QLV may predict negative stress, in contrast to data of the quick release tests, while RVE predicts no such negative stress. The results are consistent with the following conclusions: (1) fully preconditioned tendon exhibits pure viscoelastic response, (2) nonlinearity of the tendon viscoelasticity is induced by gradual recruitment of its fibers, (3) a new structure-based RVE theory is a reliable representation of the tendon viscoelastic properties under both stress relaxation and creep tests, and (4) the QLV theory is equivalent to the RVE one (and valid) only under deformations in which no fibers buckle. The results also suggest that the collagen fibers themselves are linear viscoelastic. PMID- 20353260 TI - Validation of a CFD methodology for positive displacement LVAD analysis using PIV data. AB - Computational fluid dynamics (CFD) is used to asses the hydrodynamic performance of a positive displacement left ventricular assist device. The computational model uses implicit large eddy simulation direct resolution of the chamber compression and modeled valve closure to reproduce the in vitro results. The computations are validated through comparisons with experimental particle image velocimetry (PIV) data. Qualitative comparisons of flow patterns, velocity fields, and wall-shear rates demonstrate a high level of agreement between the computations and experiments. Quantitatively, the PIV and CFD show similar probed velocity histories, closely matching jet velocities and comparable wall-strain rates. Overall, it has been shown that CFD can provide detailed flow field and wall-strain rate data, which is important in evaluating blood pump performance. PMID- 20353261 TI - The effect of flash freezing on variability in spinal cord compression behavior. AB - The compression behavior of spinal cord tissue is important for understanding spinal cord injury mechanics but has not yet been established. Characterizing compression behavior assumes precise specimen geometry; however, preparing test specimens of spinal cord tissue is complicated by the extreme compliance of the tissue. The objectives of this study were to determine the effect of flash freezing on both specimen preparation and mechanical response and to quantify the effect of small deviations in specimen geometry on mechanical behavior. Specimens of porcine spinal cord white matter were harvested immediately following sacrifice. The tissue was divided into two groups: partially frozen specimens were flash frozen (60 s at -80 degrees C) prior to cutting, while fresh specimens were kept at room temperature. Specimens were tested in unconfined compression at strain rates of 0.05 s(-1) and 5.0 s(-1) to 40% strain. Parametric finite element analyses were used to investigate the effect of specimen face angle, cross section, and interface friction on the mechanical response. Flash freezing did not affect the mean mechanical behavior of the tissue but did reduce the variability in the response across specimens (p<0.05). Freezing also reduced variability in the specimen geometry. Variations in specimen face angle (0-10 deg) resulted in a 34% coefficient of variation and a 60% underestimation of peak stress. The effect of geometry on variation and error was greater than that of interface friction. Taken together, these findings demonstrate the advantages of flash freezing in biomechanical studies of spine cord tissue. PMID- 20353262 TI - A new observation on the stress distribution in the coronary artery wall. AB - The stress distribution in the vessel wall has an important bearing on vascular function in health and disease. We studied the relationship between the transmural stress distribution and the opening angle (OA) to determine the stress gradient. The simulation of wall stress was based on transmural measurements of strain and material properties of coronary arteries in reference to the zero stress state. A one-layer model with material constants of the intact vessel was used to calculate the circumferential stress distribution. A sensitivity analysis using both one- and two-layer models (intima-media and adventitia layers) was carried out to study the effect of the OA on the circumferential stress distribution and average circumferential stress. A larger OA always shifts the circumferential stress from the intima-media to the adventitia layer. We report a new observation that the circumferential stress at the adventitia may exceed that at the intima at physiological loading due to the larger OA in the porcine coronary artery. This has important implications for growth and remodeling, where an increase in opening angle may shift excessive stress from the inner layer to the outer layer. PMID- 20353263 TI - In vitro stretches of the mitral valve anterior leaflet under edge-to-edge repair condition. AB - Mitral valve edge-to-edge repair (ETER) alters valve mechanics, which may impact efficacy and durability of the repair. The objective of this paper was to quantify stretches in the central region of the anterior leaflet of the mitral valve after ETER with a single suture and 6 mm suture. Sixteen markers, forming a 4x4 array, were attached onto the central region of the mitral valve anterior leaflet. The mitral valve was subjected to ETER with a single suture and 6 mm suture, and mounted in an in vitro flow loop simulating physiological conditions. Images of the marker array were used to calculate marker displacement and stretch. A total of 9 mitral valves were tested. Two peak stretches were observed during a cardiac cycle, one in systole and the other in diastole under mitral valve edge-to-edge repair condition. The major principal (radial) stretch during systole was significantly greater than that during diastole. However, there was no significant difference between the minor principal (circumferential) stretch during diastole and that during systole. In addition, there were no significant differences in the radial and circumferential, or areal stretches and stretch rates during diastole between the single suture and 6 mm suture. The ETER subjects the mitral valve leaflets to double frequency of loading and unloading. Minor change in suture length may not result in a significant load difference in the central region of the anterior leaflet during diastole. PMID- 20353264 TI - Goldmann tonometry correction factors based on numerical analysis. AB - With the world's aging population, it is expected that the number of people affected by glaucoma, the second most common cause of irreversible blindness, will increase considerably. Current knowledge on glaucoma progression relates elevation of the intraocular pressure (IOP) to optic nerve damage and hence visual impairment. For this reason, IOP measurement in tonometry has become an essential part of routine eye examinations needed for the diagnosis and management of the disease. The accuracy of the current reference standard in tonometry, the Goldmann applanation tonometer, is known to be affected by the natural variations in corneal thickness, curvature, and material properties. Earlier studies attempted to quantify these effects and produced correction factors that considered the variations in each one of these parameters separately, and no guidance was given as to how to combine the effects of variations in more than one parameter. The present research attempted to address this gap by conducting a multidimensional numerical study that considered variations in thickness, curvature, material properties, and IOP, and used the results to develop a single correction equation that considered these parameters simultaneously. The results of the analysis and the correction equation were validated successfully against the outcome of earlier clinical and mathematical studies on the effect of individual parameters, and the correction equation was presented in a simple form suitable for clinical application. PMID- 20353265 TI - Accuracy of inertial motion sensors in static, quasistatic, and complex dynamic motion. AB - Inertial motion sensors (IMSs) combine three sensors to produce a reportedly stable and accurate orientation estimate in three dimensions. Although accuracy has been reported within the range of 2 deg of error by manufacturers, the sensors are rarely tested in the challenging motion present in human motion. Their accuracy was tested in static, quasistatic, and dynamic situations against gold-standard Vicon camera data. It was found that static and quasistatic rms error was even less than manufacturers' technical specifications. Quasistatic rms error was minimal at 0.3 deg (+/-0.15 deg SD) on the roll axis, 0.29 deg (+/-0.20 deg SD) on the pitch axis, and 0.73 deg (+/-0.81 deg SD) on the yaw axis. The dynamic rms error was between 1.9 deg and 3.5 deg on the main axes of motion but it increased considerably on off-axis during planar pendulum motion. Complex arm motion in the forward reaching plane proved to be a greater challenge for the sensors to track but results are arguably better than previously reported studies considering the large range of motion used. PMID- 20353266 TI - Increase in opening angle in hypertension off-loads the intimal stress: a simulation study. AB - The stress distribution in the vessel wall has important bearing on vascular function including intima, media, and adventitia. The residual strain in the vessel wall has been thought to largely normalize the transmural stress distribution with slightly higher values at the intima. In hypertension, the compensatory increase in opening angle is thought to maintain a uniform stress distribution. We have recently shown that the circumferential stress at adventitia may exceed that at intima at physiological loading due to large opening angle (OA) in normal porcine coronary arteries. The objective of this study was to show that increases in opening angle subsequent hypertension can further shift the stress from the intima to the adventitia. The change in stress distribution during acute hypertension was calculated using available data on the changes in vessel geometry, material property, and internal pressure during hypertension. It was found that the increase in OA following acute hypertension off-loads the stress from intima to adventitia, therefore, relieving some of the stress increase in the intimal layer induced by the sudden pressure increase. This has important implications for hypertension where it may shift the excessive stress from the inner layer to the outer layer. This may be a protective mechanism for the intima layer in hypertension. PMID- 20353268 TI - Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays. AB - Clusterin (CLU) is expressed in a wide variety of human tissues and fluids. Overexpression of cytoplasmic clusterin (sCLU) has been implicated in cancer development and progression. The aim of the present study is to evaluate the association of sCLU overexpression with clinicopathological features of human gastric carcinomas (GC).We constructed a gastric cancer tissue microarray containing 173 primary gastric carcinomas and 70 paired non-neoplastic mucosa specimens. The expression of sCLU was studied by immunohistochemistry. The correlations between sCLU expression and clinicopathological features, p53 abnormality, as well as Ki67 activation were analyzed. Overexpressions of sCLU was detected in 28.5% (n=165) of primary GCs by immunohistochemical staining, but not in non-neoplastic mucosa. Clinical association study found that overexpression of sCLU was significantly correlated with lymph-node metastasis (p < 0.001), tumor invasion (p < 0.001) and TNM stage (p < 0.001). In Kaplan-Meier survival analysis, overexpression of sCLU was significantly correlated with unfavorable survival in advanced GCs (p < 0.03). Furthermore, the association of sCLU with abnormal expression of p53 was ascertained. These results suggested that overexpression of sCLU was involved in the progression of GC and it's oncogenic function might be associated with p53 abnormality. Overexpression of sCLU seems to be related with patient's shorter survival in late stage GC. PMID- 20353269 TI - Interaction between estrogens and androgen receptor genes microsatellites, prostate-specific antigen and androgen receptor expressions in breast cancer. AB - The role of estrogen and androgen receptors signaling in breast cancer is widely accepted, but the interrelations between them are not well understood. It was suggested that PSA could be a marker of endogenous balance between androgens and estrogens. In this context, we intended to investigate the potential of relationship between polymorphic tandem repeats (CAG, TA and CA) in AR (androgen receptor), ERalpha (estrogen receptor alpha) and ERbeta (estrogen receptor beta) genes and the immunoexpression of PSA and AR proteins. We assessed also the possible influences of CAG, TA, and CA variables and other available prognostic factors (ER, PR, AR, HER2/neu, PSA expression, and nodal status) on disease-free survival. We assessed the polymorphic tandem repeats lengths by genotyping, followed by high-resolution denaturing polyacrylamide gel electrophoresis in 163 breast cancers. Immunohistochemistry was performed to assess the expressions of AR, PSA, ER, PR and HER2/neu proteins. Our results showed that PSA was correlated with the length of CA repeats in the 3'-untranslated region of ERbeta, shorter CA repeats being correlated with PSA expression (p=0.03). AR immunoexpression was correlated with CAG repeats on AR gene, higher number of repeats being linked to a higher AR immunoexpression (p=0.04). Performing logistic regression to investigate relationships with prognosis, we observed that PSA immunoexpression (p=0.004), the nodal status (p-<0.001) and marginally, longer TA repeats (p=0.05) were correlated with increased disease-free survival. AR expression presented a low statistical value (p=0.054) in predicting evolution and was not entered into the multivariate regression analysis. Altogether, our findings supports the hypothesis that estrogens, through both alpha and beta-receptors variants are mediating the AR signaling pathway. PMID- 20353270 TI - In vitro and in vivo effects of reovirus on HPV16-transformed mice cells. AB - Oncolytic viruses are examined to serve as anticancer therapeutics. It is expected that in addition to direct oncolytic effect their action will also help eliciting a solid antitumor immunity. In presented series of experiments we have employed two HPV16-transformed mouse (strain C57/B6) cell lines, TC-1 and MK16/III/ABC (MK16), and reovirus type 3, strain Dearing (RV). Both cell lines are highly susceptible to RV and produce large amounts of infectious virus in vitro while normal human are not susceptible to RV. Still, some differences were encountered. TC-1 cells produced moderately lesser amounts of infectious virus, but, paradoxically, were more efficient producers of delta1 antigen of RV and as a consequence of virus infection died more rapidly than simultaneously infected MK16 cells. Minor differences between the cell lines were observed in the percentage of cells arrested in theG2/M phase of the cell cycle and in some markers of apoptosis. When inoculating high doses (5x106) of infected cells (MOI 10 PFU/cell) into syngeneic animals their oncogenic activity was strongly suppressed, nearly completely in the case of MK16 cells and somewhat less efficiently in the case of more oncogenic TC-1 cells. Immunizing experiments in which non-oncogenic doses (106) of RV infected TC-1 cells were tested in parallel with the same doses of irradiated cells brought surprising results. When immunized animals were challenged with TC-1 cells, the irradiated cells proved to be a much better immunogen that the infected cells. However, when challenged with MK16 cells the opposite was true. It is believed that this difference was associated with the different biological properties of the cell lines tested. KEYWORDS: reovirus type 3, HPV16-transformed mouse cell lines, apoptosis, cell cycle, immunization/challenge experiments. PMID- 20353271 TI - Telomere length, molecular cytogenetic findings, and immunophenotypic features in previously untreated patients with B-chronic lymphocytic leukemia. AB - Telomere length was evaluated by terminal repeat fragment method in 66 previously untreated patients with B-chronic lymphocytic leukemia (B-CLL) to ascertain whether telomere shortening was associated with genomic aberrations, immunoglobulin variable heavy chain (IgVH) mutational status, CD38 and ZAP-70 expression, and telomerase activity. Chromosomal aberrations were present in peripheral blood cells of 73% patients (48/66), no difference in telomere length between patients with good and intermediate prognosis according to cytogenetics was found. Association between telomere length and IgVH mutational status, ZAP-70 and CD38 expression was proved as significantly shorter telomeres in patients with unmutated IgVH status (p=0.01) and ZAP-70 positivity (p=0.01) and CD38 positivity (p=0.05) were detected. Telomerase activity was positive in 11 patients out of 21 examined, correlation between telomere length and telomerase activity was found (p=0.05). Telomere length and telomerase activity in combination with other prognostic parameters complete the risk profile of B-CLL patients and might serve for an easy decision on optimal treatment strategy. KEYWORDS: B-chronic lymphocytic leukemia, telomere length, telomerase activity, chromosomal aberrations, prognosis. PMID- 20353272 TI - Nuclear translocation of telomerase reverse transcriptase: a critical process in chemical induced hepatocellular carcinogenesis. AB - Telomerase, a ribonuclearprotein complex, functions not only in cancer development but also in apoptosis, and senescence. As a catalytic subunit of telomerase, telomerase reverse transcriptase (TERT) has been confirmed to regulate telomerase activity in a rate-limiting manner. Although a lot of work has been done, the dynamic state of TERT protein and the relationship with telomerase have not been delineated systematically in cancer development. The purpose of this study was to do such an exploration. To investigate the role of TERT in the in vivo carcinogenesis, we performed immunofluorescence and Western blot analysis, respectively, to detect the alteration of TERT status as well as telomeric repeat amplification protocol (TRAP) assay to detect telomerase activity in diethyl nitrosoamine (DENA) induced rat hepatocellular carcinoma (HCC). The course of cancer development was divided into three main stages, which were inflammation ( <12 weeks), hepatocirrhosis (15 weeks), and hepatocarcinoma (18-21 weeks). In normal liver and its early inflammatory stage, concomitant with a weak positive TERT signal, which was detected exclusively in the cytoplasm, telomerase activity was very low at this stage. However, in late hepatocirrhosis and particularly cancer stage, high levels of TERT expression (P = 0.044 and P = 0.001, respectively) and telomerase activity (P = 0.02 and P = 0.01, respectively) were observed following TERT nuclear translocation. Our data suggest that TERT protein might regulate telomerase activity. TERT translocation from cytoplasm to the nucleus might be a turning point in cancer development. Therefore, TERT translocation might be more useful than TERT expression level and telomerase activity in predicting the progression of HCC. PMID- 20353273 TI - Transcriptional inactivation of secreted frizzled-related protein 1 by promoter hypermethylation as a potential biomarker for non-small cell lung cancer. AB - Epigenetic silencing of secreted frizzled-related protein (SFRP) genes, antagonists of the WNT pathway, contributes to the pathogenesis of several cancers including non-small cell lung cancer (NSCLC). We hypothesize that methylation analysis of SFRPs family could improve their use as a panel of biomarkers for diagnosing and staging of NSCLC in China. The expression of four SFRP members (SFRP1, 2, 4, and 5) in NSCLC samples was screened by RT-PCR and quantitative real-time PCR. Only SFRP1 was significantly downregulated in NSCLC, as compared to adjacent normal tissues and benign pulmonary disease tissues (P=0.006). Promoter hypermethylation of SFRP1 was found in 32.1% (25/78) NSCLC specimens and was closely correlated with loss of expression, besides SFRP1 hypermethylation was associated with lymph metastasis (P=0.039) and disease progression within one year (P=0.027). Furthermore, methylated SFRP1 was detected in 28.2% (22/78) of plasma samples from NSCLC patients while only 4% (2/50) in cancer-free controls, and the concordance of SFRP1 methylation status in tumor tissues and corresponding plasmas was satisfactory (P <0.001). In conclusion, epigenetic inactivation of SFRP1 is a common event contributing to lung carcinogenesis and maybe used as a potential biomarker for NSCLC in Chinese population. PMID- 20353274 TI - Increased 18F-FDG uptake and expression of Glut1 in the EMT transformed breast cancer cells induced by TGF-beta. AB - As carcinomas progress, the tumors may lose epithelial morphology and acquire mesenchymal characteristics typically called epithelial-mesenchymal transition (EMT), which is commonly associated with increased cell migration, enables cells to dissociate from their original tissue and form metastasis in distant organs. In addition to molecular and morphologic changes, the EMT transformed cells also showed the change of sensitivity to chemotherapeutics. In order to detect the EMT transition in vivo clinically, we detected the change of metabolism of MCF-7 cells after being induced by TGF-beta to form EMT condition by MTT and 18F-FDG uptake. PMID- 20353275 TI - Prognostic stratification using F-18 FDG PET/CT in patients with advanced stage (stage III and IV) non-small cell lung cancer. AB - F-18 FDG PET could provide prognostic information in patients with advanced resectable NSCLC. In the current study, we investigated the prognostic implication of F-18 FDG PET after chemotherapy in patients with advanced stage III and IV NSCLC. A retrospective review identified 19 patients with advanced stage (stage III and IV) NSCLC who received F-18 FDG PET/CT at diagnosis of cancer and after chemotherapy. The visual response and changes of SUV max before and after treatment on survival was investigated using Kaplan-Meier and Cox proportional hazard regression analyses. The median follow-up time was overall 24.8 month (range, 9.4-59.8 month), for surviving patients 41 month (range, 34.1 59.8 month), and for deceased patients 16.6 month (range, 9.4-29.4 month). Overall survival after baseline F-18 FDG PET/CT at 1 year was 73.7% and at 2 year was 47.4%. Comparing patients with and without F-18 FDG PET/CT response, there was statistically significant difference in overall survival between the 2 groups (median survival time, responder, 29.4 month; non-responder, 14.2 month, Chi(2)=3.91, p=0.048). Also, using the %DeltaSUV(max) for the comparison, significant difference was existed in overall survival between 2 groups (Chi(2)=12.6, p=0.0004). When the tumor reveals more than 17.85% reduction of %DeltaSUV(max), the survival could be predicted (AUC, 0857; standard error, 0.0866; 95% confidence interval, 0.622-0.971; sensitivity, 75%; specificity, 100%; p=0.0001). With Cox proportional hazard model, %DeltaSUV(max) was determined to be a potent prognostic factor for survival (Chi(2), 12.09; p=0.0005). In conclusion, using the visual and quantitative analyses of F-18 FDG PET/CT, the responder to chemotherapy in advanced stage NSCLC patients had a better prognosis. Moreover, the potent predictor of prognosis in advanced stage NSCLC patients was %DeltaSUV(max). PMID- 20353276 TI - High-resolution melting analysis of PCDH10 methylation levels in gastric, colorectal and pancreatic cancers. AB - Protocadherins are celladhesion molecules with 6 or 7 cadherin motifs in their extracellular domain and various cyotoplasmic domains. PCDH10 was characterized a novel tumor suppressive gene in and was epigenetically silenced in multiple haematologic malignancies as well as some solid tumors such as gastric cancer, nasopharyngeal carcinoma and esophageal carcinoma. High-resolution melting (HRM) analysis has been used as a novel tool for analysis of promoter methylation. In our study, we used HRM analysis to detect the methylation levels of PCDH10 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers and equal number of adjacent normal tissues. The frequency of PCDH10 methylation in all three types of cancers was significantly higher than that in normal tissues. Consistent with previous reports, expression levels of PCDH10 were inversely correlated with methylation levels. But we didn't find significant association between PCDH10 methylation status and TNM staging in all three types of cancers. In summary, application of HRM analysis to large amount of clinical samples proves to be a fast and high-throughput way to investigate the epigenetic status of PCDH10. And this is the first study to evaluate the prevalence of PCDH10 methylation based on large amount of tumor samples, showing that epigenetic regulation of PCDH10 was associated with carcinogenesis. PMID- 20353277 TI - Annexin A1 expression and its prognostic significance in human breast cancer. AB - Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and is considered to play an important role in tumorigenesis. However, the correlation between ANXA1 expression and tumor clinicopathological features in patients with breast cancer remains unclear. This study investigated the prognostic value of ANXA1 protein as breast cancer marker. Tissue microarray blocks, containing 20 cases of non-tumor breast tissue, 20 cases of benign breast lesion and 135 cases of breast cancer (107 with lymph node metastasis), were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemistry. In non-tumor tissue and benign breast lesions, myoepithelial cells showed strong expression of ANXA1. Negative ANXA1 expression was significantly associated with advanced disease stage (P<0.05), especially pathological-N stage (P<0.01). The patients with loss of ANXA1 expression in tumor tissues showed a significantly worse overall survival compared with positive ones (P<0.05). ANXA1 did not correlate well with estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Moreover, the level of ANXA1 expression in lymph node metastases was higher than corresponding primary breast cancer. These results suggest that ANXA1 may play a multifaceted role in breast cancer development, progression, and metastases. PMID- 20353278 TI - Is there any venous gradient in serum thyroglobulin levels in patients with differentiated thyroid cancer? AB - Some patients with differentiated thyroid cancer (DTC) have high serum thyroglobulin (Tg) levels although no evidence of disease can be detected on radioiodine scanning or other imaging methods. The aim of this study is to determine whether a gradient exists between the Tg levels of venous samples adjacent to primary tumour and systemic circulation. Twenty-six patients underwent thyroidectomy and/or lymph node dissection for primary and recurrent DTC. To detect Tg levels, blood samples were concurrently collected via venipuncture from the internal jugular vein adjacent to the tumor and ipsilateral antecubital vein. Serum Tg level was measured by a chemiluminescence assay. Tg levels were significantly higher in the adjacent internal jugular vein compared to the ipsilateral antecubital vein (p=0.001). The ratio of mean Tg values was higher 2.4-fold in the internal jugular vein than antecubital vein (median Tg ratio: 2.0:1; range, 0.7-29.6). Documentation of a venous gradient in Tg levels in patients with DTC is a new investigational topic. According to the results of this prospective study, venous sampling for Tg may be a useful tool to localize recurrent or perhaps persistent DTC in the neck for patients who have no detectable disease on radioiodine scans or other imaging studies. PMID- 20353279 TI - MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients. AB - MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0.016), miR-222 (p=0.038), miR-181b (p=0.036), miR-181c (p=0.043) and miR-128a (p=0.001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0.001). MiR 181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0.016; p=0.047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients. PMID- 20353280 TI - Treatment of newly diagnosed patients with acute promyelocytic leukemia with modified spanish treatment protocol. AB - The results of treatment of acute promyelocytic leukemia, when combination ATRA + chemotherapy is used in induction and maintainance therapy and risk adapted strategy applied in consolidation, improved at present time. Enhanced supportive therapy also contribute to improved outcome of APL patients. 3 - year relapse free, overall survival and clinical and biological presenting features of APL patients were evaluated. Since January, 2001 till March, 2009, 32 patients treated with modified spanish treatment scheme were assessed. After june 2003 risk adapted strategy in protocol therapy according to spanish treatment group with ATRA and anthracyclines in consolidation therapy in high and intermediate risk patients was used. Cytoreduction therapy in patients with initially high leukocyte count was the modification of spanish treatment scheme. 29 (90.6%) patients achieved complete hematologic remission, 2 (6.3 %) molecular relapses were observed, death was observed in 4 patients (12.5%). The estimated 3-year OS was 90.6%; 95% CI (80.5%-100.0%), and estimated 3-year RFS was 95.5 %; 95 % CI (86.8%-100.0%). Survival results correspond with other published clinical studies. The number of relapses was slightly lower and the incidence of ATRA syndrome (50%) was higher when compare with the results of other study groups. Current recommendations for treatment with risk-adapted strategy for patients with newly diagnosed acute promyelocytic leukemia resulted in our patients group to comparable outcome and good compliance like in other published studies. PMID- 20353281 TI - Population-based study of BRCA1/2 mutations: family history based criteria identify minority of mutation carriers. AB - The two major susceptibility genes, BRCA1 and BRCA2, are involved in hereditary breast and ovarian cancer syndrome. Early detection of mutation carriers has crucial clinical importance, as it allows identification of women who may benefit from intensive clinical follow-up or prophylactic surgery. Generally accepted inclusion criteria for BRCA1/2 mutation testing are based either upon family history of breast or ovarian cancer or young age at cancer diagnosis. In order to analyze the impact of BRCA1/2 mutations on breast cancer development in the Czech population and to confront the clinical and histopathological data of mutation carriers with current criteria for mutation testing we examined the frequency of mutations in unselected breast cancer cases. Mutational analysis of BRCA1/2 genes performed in 679 unselected female breast cancer patients included all recurrent deleterious alterations previously identified in the Prague area and truncating mutations in the whole exon 11 of BRCA1. Within analyzed gene sequences more than 80% of mutations were identified previously in high-risk patients. A total of 16 breast cancer patients (2.4%) carried a mutation. BRCA1 mutations were identified in 14 (2.1%) whereas BRCA2 in 2 (0.3%) women. Family history of ovarian cancer was a strong predictor of a BRCA1/2 mutation (OR = 8.3; p = 0.01), however, family history of breast cancer was not indicative of carrier status. A significant association between medullary breast cancer and mutation status was observed. Current criteria for BRCA1/2 mutation testing would distinguish only 6 out of 16 (37.5%) carriers identified in our study. Ten breast cancer patients with confirmed BRCA1/2 germ-line mutation exhibited no clinical characteristics that would predict their carrier status. Therefore, we believe that the testing for BRCA1/2 mutations in the Czech Republic may not be restricted only to high risk patients. Our results indicate that analysis of locally prevalent BRCA1/2 mutations in all breast cancer patients might extend substantially the percentage of identified mutation carriers. PMID- 20353282 TI - The Northland Regional-Rural program (Pukawakawa): broadening medical undergraduate learning in New Zealand. AB - CONTEXT: Medical schools in Australasia are using a range of initiatives to increase the number of graduates working outside major centres. This article describes the design, implementation and selected outcomes of the University of Auckland's regional-rural program, Pukawakawa. The program is based on a 'hub and spoke' model located in Northland, New Zealand, an area of 150,000 people with a high proportion of Maori and relative social deprivation. ISSUE: A 27 week curriculum for 20 volunteer year 5 students was developed in collaboration with stakeholders. The curriculum had three main attachments: integrated care and general practice; women and children's health; and secondary care. These were designed to promote better continuity with patients and supervisors, and a greater likelihood of a rural career. Funding for Pukawakawa came from existing government grants with a contribution from the Northland District Health Board. A mixed-methods evaluation of the first year was conducted. LESSONS LEARNED: Staff and students reported high levels of satisfaction with the program and students performed at an academic level similar to their standard-program counterparts. Early reservations related to the experience of supervisors with assessment standards, and the resourcing required to maintain academic equivalence across sites. It is too soon to detect whether students' career aspirations are altered as a result of Pukawakawa. Areas for future study include student preparedness for later stages of training, career destination, how students learn in this environment and the benefits to the Northland region more broadly. PMID- 20353283 TI - Upper limb virtual rehabilitation for traumatic brain injury: initial evaluation of the elements system. AB - PRIMARY OBJECTIVE: To evaluate the effectiveness of a tabletop virtual-reality (VR) based upper-limb rehabilitation system (called Elements) for promoting movement skill in patients with TBI. RESEARCH DESIGN: An ABA case study design with multiple baselines was employed. Baseline performance in this design is contrasted against the results during the treatment phase. RESEARCH METHODS: Three patients with TBI participated in 12 1-hour sessions of VR-based training. The VR system consisted of a 42-inch tabletop LCD, camera tracking system and tangible user interface. The system requires participants to move an object to cued locations while receiving augmented movement feedback to reinforce speed, trajectory and placement. Upper limb performance was assessed using these three system-measured variables and standardized tests. Trends in the time-sequence plots for each patient were assessed by sight inspection of smoothed data and then by statistical analyses. RESULTS: Participants demonstrated improvements on movement accuracy, efficiency and bimanual dexterity and mixed improvement on speed and other measures of movement skill. CONCLUSION: Taken together, the findings demonstrate that the Elements system shows promise in facilitating motor learning in these TBI patients. Larger scale trials are now deemed a viable step in further validating the system. PMID- 20353284 TI - Acute management of acquired brain injury part I: an evidence-based review of non pharmacological interventions. AB - PRIMARY OBJECTIVE: To review the literature on non-pharmacological interventions used in acute settings to manage elevated intracranial pressure (ICP) and minimize cerebral damage in patients with acquired brain injury (ABI). MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand-searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations made. RESULTS: Five non-invasive interventions for acute ABI management were assessed: adjusting head posture, body rotation (continuous rotational therapy and prone positioning), hyperventilation, hypothermia and hyperbaric oxygen. Two invasive interventions were also reviewed: cerebrospinal fluid (CSF) drainage and decompressive craniectomy (DC). CONCLUSIONS: There is a paucity of information regarding non-pharmacological acute management of patients with ABI. Strong levels of evidence were found for only four of the seven interventions (decompressive craniectomy, cerebrospinal fluid drainage, hypothermia and hyperbaric oxygen) and only for specific components of their use. Further research into all interventions is warranted. PMID- 20353285 TI - In uno omnia: anti-thrombotic agents in challenging comorbidities. AB - BACKGROUND: Recurrent bleedings of cavernous malformations are quite frequent and frightful: survival is especially at risk in patients with brainstem cavernous malformations who cannot benefit from neurosurgical treatments. Nevertheless, pragmatic recommendations to prevent recurrent bleedings are still lacking, raising some questions on the daily clinical management of the above patients. METHODS: This study reports the case of a 59 year-old woman presenting with past recurrent bleedings from a brainstem cavernous malformation and with indication to start an anti-thrombotic treatment as a consequence of a developing coronary heart disease. Surprisingly, any suggestion about the usage of otherwise indicated anti-platelet treatment and anti-coagulation in patients with cavernous malformations was found in the literature. RESULTS: The authors faced a therapeutical dilemma with this patient, whose survival would be really at risk because of a 'time bomb in her brainstem'. CONCLUSIONS: This experience confirms the lack of clear pragmatic recommendations in the clinical management of these patients, whose treatment still represents a medical challenge. PMID- 20353286 TI - Experiences in laparoscopic removal of upper ureteral stones: multicenter analysis of cases, based on the TurkUroLap Group. AB - BACKGROUND AND PURPOSE: Laparoscopic surgery for ureteral stones was restricted to special cases-those with large or impacted ureteral stones. We present special cases of patients who underwent laparoscopic ureterolithotomy at various clinics in Turkey. PATIENTS AND METHODS: Forty-one patients were included in the study from five urology clinics in which laparoscopic surgery was being performed. After a disease-specific history and physical examination, age and sex were recorded. The mean patient age was 41.8 years (30 men and 11 women). Urinalysis, determination of creatinine level, intravenous urography, and ultrasonography were performed. The parameters of stone size, presence of hydronephrosis, previous shockwave lithotripsy, previous ureteroscopic stone therapy, type of laparoscopic approach, operative time, ureteral incision, insertion of a Double-J stent, amount of drainage, hospitalization period, and perioperative complications were evaluated. RESULTS: Mean ureteral stone size was 22 mm. The retroperitoneoscopic approach was preferred in 35 (85.3%) patients, while the transperitoneal approach was used in 6 (14.7%) patients. Grade I hydronephrosis was detected in 4 patients, grade 2 in 22 patients, and grade 3 in 12 patients. In six patients, a history of shockwave lithotripsy was confirmed. The ureteral wall was incised with a cold knife in 5, scissors in 16, J-hook in 3, and a monopolar or bipolar dissector in 17 patients. In six patients, a Double-J stent was inserted, while in one patient, the operation was converted to an open procedure. The mean operative time was 124 minutes. The mean amount of drainage was 220 ml. Mean hospitalization time was 4.8 days. In five (12.5%) of seven patients, persistent drainage was a major complication that was managed by insertion of a Double-J stent. All patients were discharged stone free. CONCLUSION: Increased hospitalization and operative time can be related to the large stone sizes and prolonged urine leakage. In our opinion, however, the overall success of laparoscopic ureterolithotomy makes it a feasible and effective procedure, especially for stones that could not be managed easily with ureteroscopic stone therapy. PMID- 20353287 TI - The involvement of microtubules and actin filaments in the intracellular transport of non-viral gene delivery system. AB - It is known that two cytoskeleton components, microtubules and actins filaments, are required for efficient endocytosis. The relative importance of these two components in the cellular uptake of 2-(dimethylamino)ethyl methacrylate (DMAEMA) DNA polyplexes was investigated in this study by applying microtubule depolymerising agent, colchicine, and actin polymerising inhibitor, cytochalasin D, in a cell transfection study. The effect of colchicine on transfection efficiency of polyplexes was found to be a time-dependent phenomenon, whereby the level of gene expression was inhibited at early stage, presumably to the disruption of a transport of vesicles along microtubules by colchicine. As time progressed, the level of gene expression was significantly enhanced relative to the control, possibly due to the failure in transport of vesicles from endosomes to late lysosomes, or due to the breakdown of nuclear membrane when mitosis was arrested at metaphase by colchicine. On the other hand, transfection efficiency was significantly reduced at all time points by cytochalasin D, which is considered to primarily affects invagination of vesicles at the early stage of endocytosis by inhibiting actin polymerisation. Further investigation to identify the endocytotic route of DMAEMA polyplexes was conducted applying clathrin- and caveolae- pathways inhibitors in cell transfection study. The results indicate that DMAEMA polyplexes were internalized primarily through clathrin-mediated pathway, with a minor fraction possibly entering cells via a caveolae-mediated pathway. PMID- 20353288 TI - Inactivation of Salmonella enterica and Listeria monocytogenes inoculated on hydroponic tomatoes using chlorine dioxide gas. AB - The main objective of this study was to determine survivability of a cocktail of three strains of Salmonella enterica (Montevideo, Javiana, and Baildon) and two strains of Listeria monocytogenes (LCDC 81-861 and F4244) on hydroponic tomatoes after treatment with chlorine dioxide (ClO(2)) gas. An initial concentration of 8 9 log cfu/mL of Salmonella and Listeria cocktails was inoculated individually, in separate experiments, on tomato skin to obtain a population of 7-8 log cfu/cm(2) after drying of the inoculums on the tomato skin. The aim was to achieve a 5 log reduction consistent with the recommendations of the National Advisory Committee on Microbiological Criteria for Foods. The tomato skins were treated with 0.1, 0.3, and 0.5 mg/L ClO(2) gas for 12 min at 22 degrees C and at the relative humidity of 90%. Untreated skin samples were processed under the same conditions. ClO(2)-gas-treated and untreated samples were recovered by an overlay method. The bottom layer contains tryptic soy agar, and the top layer consists of xylose lysine-desoxycholate agar or modified Oxford antimicrobial supplement agar for Salmonella and Listeria, respectively. More than a 5 log reduction in Salmonella and Listeria was observed on the tomato skin surfaces after treatment with 0.5 mg/L ClO(2) gas for 12 min. Treatment with 0.5 mg/L ClO(2) gas for 12 min also delayed the growth of natural microflora on tomato surfaces and extended the shelf life of tomatoes by 7 days during storage at 22 degrees C, compared with the untreated control. These results revealed that ClO(2) gas is a promising antimicrobial technology for fresh tomato skin surfaces. PMID- 20353289 TI - Prevalence and concentration of Cryptosporidium oocysts in beef cattle paddock soils and forage. AB - Cryptosporidium is a parasitic protozoan of great interest because of its widespread occurrence in surface waters, high degree of infectivity, and difficulty of risk management associated with its presence and control. Information about environmental loading and seasonal prevalence of Cryptosporidium oocysts is important for development of watershed management plans to protect public health. Healthy adult beef cattle are known to shed oocysts into the environment, and Cryptosporidium oocysts are often present all year in streams and groundwater in livestock agriculture areas. Surface soil and forage samples from 12 Virginia, United States, paddocks were analyzed bimonthly over 3 years for the presence and concentrations of Cryptosporidium oocysts. Half of the paddocks were grazed by stocker beef from November to September. The other half were managed for hay, but were grazed for a few days by the same animals in late fall and early spring to clean up late fall forage regrowth. Annual mean oocyst prevalences in soil were 57.9% and 48.4% in pasture and hay paddocks, respectively. Mean annual oocyst prevalences on forage were 52.4% and 40.5% in pasture and hay paddocks, respectively. Prevalence and concentration of oocysts on hay forage was highest in summer. Oocyst concentrations increased with increasing prevalences in both management systems. Wild animals appeared to be efficient vectors for oocyst distribution among paddocks. Canopy management, short-cycle rotational grazing, and control of wildlife are potential strategies for reduction of Cryptosporidium oocysts in pasture and lessening risk of contamination of water supplies, but further studies are needed before recommendations can be made. PMID- 20353290 TI - The effect of clinical outbreaks of salmonellosis on the prevalence of fecal Salmonella shedding among dairy cattle in New York. AB - The objective of this study was to determine if the within-herd prevalence of fecal Salmonella shedding is higher in dairy herds with clinical outbreaks of disease, as compared to herds with subclinical infections only. Data were collected prospectively from dairy herds throughout New York that had at least 150 lactating cows and that received clinical service from participating veterinarians. After enrollment, Salmonella surveillance consisted of both environmental screening and disease monitoring within the herd. Herds positive by either environmental or fecal culture were sampled during three visits to estimate the within-herd prevalence of Salmonella. We characterized isolates by serovar and antimicrobial resistance pattern. Among 57 enrolled herds, 44 (77%) yielded Salmonella-positive samples during the study period; 27 (61%) of the positive herds had Salmonella isolated from environmental samples only, and 17 (39%) had one or more laboratory-confirmed clinical cases. The within-herd prevalence of fecal Salmonella shedding ranged from 0 to 53%. Salmonella Cerro was the predominant serovar, accounting for 56% of all isolates. Antimicrobial resistance ranged from zero to nine drugs, and 14 (32%) of the positive farms generated multidrug-resistant isolates. Herds with laboratory-confirmed clinical cases had a higher prevalence of fecal Salmonella shedding than herds that only generated positive environmental samples, as estimated by a Poisson regression model (prevalence ratio, 2.7; p = 0.01). An association between dairy herd outbreaks of salmonellosis and a higher prevalence of asymptomatic shedding should help guide strategies for reducing the public health threat of Salmonella, as the ability to recognize high-risk herds by clinical laboratory submissions presents an obvious opportunity to maximize food safety at the preharvest level. This is in contrast with other foodborne zoonotic pathogens, such as Campylobacter jejuni and Escherichia coli O157:H7, which occur widely in adult cattle without accompanying clinical disease. PMID- 20353291 TI - Antitumor effect of folate-targeted liposomal doxorubicin in KB tumor-bearing mice after intravenous administration. AB - The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) overexpressing tumors in vitro, particularly in KB human carcinoma cells. However, there are few studies evaluating the in vivo efficacy of FTL-Dox in KB murine xenograft models. In this study, we investigated the antitumor activity of FTL-Dox injected intravenously in mice bearing KB tumors. Folate ligands comprising of folate-polyethyleneglycol distearoylphosphatidylethanolamine (FA-PEG-DSPE) were synthesized with different MW PEG. To design an optimum FTL-Dox formulation for therapeutic studies, we prepared various FTLs and characterized their in vitro targeting and in vivo tissue biodistribution. Mice were administered a single intravenous injection of free Dox, nontargeted PEGylated liposomal Dox (PL-Dox), or FTL-Dox. FTLs and PLs accumulated similarly in tumor tissue, despite FTLs' faster clearance from circulation. Mice treated with FTL-Dox 20 mg/kg had a slightly greater tumor growth inhibition and almost a 50% increase in life span than mice receiving PL Dox 20 mg/kg (P = 0.0121; log-rank test). We conclude that FTLs administered systemically have the potential to enhance the delivery of anticancer drugs in vivo; however, their removal by FR expressing normal tissues may have to be blocked if the benefits of tumor targeting are to be realized. PMID- 20353292 TI - Results of effectiveness trials of PRO 2000 gel: lessons for future microbicide trials. PMID- 20353293 TI - Laboratory preparedness: building a cornerstone for global surveillance. PMID- 20353296 TI - Identification of adhesin-receptor interactions driving bacterial translocation through M cells. PMID- 20353295 TI - Fidaxomicin: a new macrocyclic, RNA polymerase-inhibiting antibiotic for the treatment of Clostridium difficile infections. AB - Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these regions. With the emergence of a hypervirulent, endemic strain, more severe disease is being recognized and is occurring in previously considered unusual patient groups. Vancomycin and metronidazole are the current mainstays for therapy of severe and nonsevere disease, respectively. Relapse is a major concern, with treatment options for these cases often difficult. Any new drug must be better than vancomycin for severe disease with fewer relapses. Fidaxomicin, a macrocyclic RNA polymerase inhibitor, has a narrow spectrum of activity, which is almost C. difficile specific. This drug appears to have a higher clinical cure rate than vancomycin, and fewer patients relapse following initial treatment. From the results of a recent Phase III trial, fidaxomicin appears to be an extremely promising drug for treating C. difficile infection and preventing relapses. PMID- 20353297 TI - Chlamydia trachomatis: small genome, big challenges. AB - Chlamydial infections are highly newsworthy, but basic research into Chlamydia trachomatis is severely hampered by a series of formidable technical barriers. This has resulted in a paucity of information with respect to the genetics and population structure of these recalcitrant bacteria. Here we present a review of what is currently known about the genomics of C. trachomatis and discuss the usefulness of molecular typing systems and the prospects of developing a pan chlamydial genome resource. PMID- 20353299 TI - Rubella virus capsid protein: a small protein with big functions. AB - Virus replication occurs in the midst of a life or death struggle between the virus and the infected host cell. To limit virus replication, host cells can activate a number of antiviral pathways, the most drastic of which is programmed cell death. Whereas large DNA viruses have the luxury of encoding accessory proteins whose main function is to interfere with host cell defences, the genomes of RNA viruses are not large enough to encode proteins of this type. Recent studies have revealed that proteins encoded by RNA viruses often play multiple roles in the battles between viruses and host cells. In this article, we discuss the many functions of the rubella virus capsid protein. This protein has well defined roles in virus assembly, but recent research suggests that it also functions to modulate virus replication and block host cell defences. PMID- 20353298 TI - Trolling for the ideal model host: zebrafish take the bait. AB - As little as 10 years ago, murine models of infectious disease were the host of choice for analyzing interactions between the pathogen and host during infection. However, not all pathogens can infect mice, nor do they always replicate the clinical syndromes observed in human infections. Furthermore, in the current economic environment, using mammalian models for large-scale screens may be less economically feasible. The emergence of the zebrafish (Danio rerio) as an infectious disease host model, as well as a model for vertebrate immune system development, has provided new information and insights into pathogenesis that, in many instances, would not have been possible using a murine model host. In this article we highlight some of the key findings and the latest techniques along with the many advantages of using the zebrafish host model to gain new insights into pathogenic mechanisms in a live vertebrate host. PMID- 20353300 TI - Prospects for defined epitope vaccines for respiratory syncytial virus. AB - The history of vaccines for respiratory syncytial virus (RSV) illustrates the complex immunity and immunopathology to this ubiquitous virus, starting from the failed formalin-inactivated vaccine trials performed in the 1960s. An attractive alternative to traditional live or killed virus vaccines is a defined vaccine composed of discrete antigenic epitopes for which immunological activities have been characterized as comprehensively as possible. Here we present cumulative data on murine and human CD4, CD8 and neutralization epitopes identified in RSV proteins along with information regarding their associated immune responses and host-dependent variability. Identification and characterization of RSV epitopes is a rapidly expanding topic of research with potential contributions to the tailored design of improved safe and effective vaccines. PMID- 20353301 TI - Contribution of oxygen-limiting conditions to persistent infection of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a versatile opportunistic human pathogen that is able to colonize a broad spectrum of different aquatic and soil habitats. In the environment and during pathogenesis, P. aeruginosa encounters oxygen-limited and anaerobic environments. Particularly during chronic infection of the cystic fibrosis lung, oxygen-limiting conditions seem to contribute to persistent infection. Oxygen limitation increases antibiotic tolerance, robust biofilms and alginate biosynthesis, which contribute to the persistence of this opportunistic pathogen. Despite the importance of anaerobic metabolism during persistent infection of P. aeruginosa, we are just beginning to understand the underlying regulatory network and the molecular basis of how anaerobic metabolism contributes to a persistent infection. A deeper understanding of the anaerobic physiology of P. aeruginosa will allow the identification of new antibiotic targets and new therapeutic strategies. PMID- 20353303 TI - Helicobacter pylori eradication therapy. AB - Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising. PMID- 20353304 TI - Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. AB - Tularemia is primarily caused by two subspecies of Francisella tularensis worldwide, ssp. tularensis (type A) and ssp. holarctica (type B), which were originally delineated by phenotypic differences. Application of molecular typing methods to investigate population structure of F. tularensis has confirmed that categorizing the two subspecies via phenotypic characteristics corresponds with genotypic differentiation. In addition, genotyping methods have demonstrated that both subspecies, type A and type B, can be further distinguished into subpopulations and, in some cases, biological relevance has been ascribed to these identified subpopulations. Genetic variation among both type A and type B subpopulations has been shown to correlate with differences in geographic distribution and has also been coupled to distinct ecological niches, animal hosts and replication foci. Among type A subpopulations, strain variation is linked to differing clinical manifestations in humans and virulence in mice. This article will highlight our current understanding of F. tularensis subpopulations, including methods for their detection, their observed epidemiologic differences, implications for public health and basic research programs, as well as future challenges yet to be solved. PMID- 20353302 TI - Tissue tropisms in group A streptococcal infections. AB - Group A Streptococcus (GAS) is a human-specific pathogen that is highly prevalent throughout the world. The vast majority of GAS infections lead to a mild disease involving the epithelial surfaces of either the throat or skin. The concept of distinct sets of 'throat' and 'skin' strains of GAS has long been conceived. From an ecological standpoint, the epithelium of the throat and skin are important because it is where the organism is most successful in reproducing and transmitting to new hosts. This article examines key features of the epidemiology, population biology and molecular pathogenesis that underlie the tissue site preferences for infection exhibited by GAS, with an emphasis on work from our laboratory on skin tropisms. Recombinational replacement with orthologous gene forms, following interspecies transfer, appears to be an important genetic step leading up to the exploitation of new niches by GAS. PMID- 20353305 TI - Small variant surface antigens and Plasmodium evasion of immunity. AB - Antigenic variation at the Plasmodium-infected erythrocyte surface plays a critical role in malaria disease severity and host immune evasion. Our current understanding of the role of Plasmodium variant surface antigens in antigenic variation and immune evasion is largely limited to the extensive work carried out on the Plasmodium falciparum var gene family. Although homologues of var genes are not present in other malaria species, small variant gene families comprising the rif and stevor genes in P. falciparum and the pir genes in Plasmodium vivax, Plasmodium knowlesi and the rodent malaria Plasmodium chabaudi, Plasmodium berghei and Plasmodium yoelii also show features suggesting a role in antigenic variation and immune evasion. In this article, we highlight our current understanding of these variant antigens and provide insights on the mechanisms developed by malaria parasites to effectively avoid the host immune response and establish chronic infection. PMID- 20353307 TI - Viability and engraftment of hematopoietic progenitor cells after long-term cryopreservation: effect of diagnosis and percentage dimethyl sulfoxide concentration. AB - BACKGROUND AIMS: We carried out a retrospective analysis of viability by diagnosis and dimethyl sulfoxide (DMSO) concentration in patients who had undergone autologous transplants using hematopoietic progenitor cells (HPC) after long-term storage (up to 17.8 years). METHODS: Viability was tested using flow cytometry for HPC that were harvested and preserved using a controlled rate freezer and 5% or 10% DMSO with human serum albumin, then stored in liquid nitrogen. Data from 262 samples were analyzed (249 myeloma patients and 13 other diagnoses): 100 consecutively thawed samples with a storage time of <1 year (all 10% DMSO), 50 consecutive samples stored for 1-4.9 years (10% DMSO), 50 samples stored for 5-9 years (5% DMSO) and all samples stored and used for transplant after >9 years (60 samples, 5% DMSO; two samples, 10% DMSO). RESULTS: No statistically significant difference in viability between the 5% DMSO and 10% DMSO groups was observed (P = 0.08), so the 1-4.9 years and 5-9 years were combined and the three groups (<1 year, 1-9 years and >9 years) were compared using an anova test. There was no difference in viability based on cryostorage period (P = 0.23) or between myeloma and other diagnoses (P = 0.45). No difference was seen in time to White blood cell (WBC) engraftment (P = 0.10) or to platelet engraftment between groups (P = 0.52). CONCLUSIONS: These data suggest that long-term storage in 5% DMSO and human serum albumin is safe. PMID- 20353308 TI - High recovery of mesenchymal progenitor cells with non-density gradient separation of human bone marrow. AB - BACKGROUND AIMS: Bone marrow (BM) is the most used source of hemopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) in both hematologic settings and regenerative medicine. We compared the feasibility and reproducibility of two gravity separation techniques, with or without the use of a density gradient, in terms of both hematopoietic and mesenchymal human BM progenitors. METHODS: A total of 16 BM samples was processed to obtain mononuclear cells (MNC) and buffy coats (BC). The efficiency of the two procedures was evaluated by recovery of white blood cells (WBC), MNC and CD34(+) cells, clonogenic assays, red blood cell (RBC) depletion, cell viability, expression of embryonic transcriptional regulators and MSC assessment. RESULTS: The two procedures yielded a comparable recovery of HSC. Non-density gradient separation (NDGS) of BM resulted in four times higher MSC recovery and higher expression of embryonic stem cell markers (Nanog and Sox2) compared with density-gradient separation (DGS). MSC derived from both procedures was comparable in terms of phenotype, differentiation and proliferation potential. CONCLUSIONS: NDGS is less time consuming, provides a better MSC enrichment and appears to be a suitable cell preparation method for clinical applications. PMID- 20353309 TI - GMP-manufactured density gradient media for optimized mesenchymal stromal/stem cell isolation and expansion. AB - BACKGROUND AIMS: Bone marrow (BM) mesenchymal stromal/stem cells (MSC) are therapeutic tools in regenerative medicine and oncology. MSC isolation is often performed starting from a separation step based on research-grade 1.077 g/mL density gradient media (DGM). However, MSC clinical application should require the introduction of good manufacturing practice (GMP) reagents. We took advantage of two novel GMP DGM with densities of 1.077 and 1.073 g/mL (Ficoll-Paque PREMIUM and Ficoll-Paque PREMIUM 1.073, respectively) to test whether these reagents could isolate MSC efficiently while simultaneously comparing their performance. METHODS: BM samples were processed using either 1.077 or 1.073 g/mL GMP DGM. BM mononucleated cell (MNC) fractions were analyzed for viability, immunophenotype, clonogenic potential, ex vivo expansion and differentiation potential. RESULTS: No differences were noticed in cell recovery and viability between the groups. Fluorescence-activated cell-sorting (FACS) analyzes on freshly isolated cells indicated that the 1.073 g/mL GMP DGM more efficiently depleted the CD45(+) fraction in comparison with 1.077 GMP DGM. Moreover, in the 1.073 group, fibroblastic colony-forming units (CFU-F) were 1.5 times higher and the final MSC yield 1.8 times increased after four passages. Both reagents isolated MSC with the expected phenotype; however, 1.073-isolated MSC showed a higher expression of CD90, CD146 and GD2. Additionally, MSC from both groups were capable of fully differentiating into bone, adipose cells and cartilage. CONCLUSIONS: Both GMP DGM enriched MSC from BM samples, suggesting that these reagents would be suitable for clinical-grade expansions. In addition, the density of 1.073 g/mL provides a significant advantage over 1.077 g/mL GMP DGM, impacting the quantity of MSC obtained and reducing the ex vivo expansion time for optimized cell-based clinical applications. PMID- 20353310 TI - A noninvasive renal fungus ball caused by Rhizopus--a previously unreported manifestation of zygomycosis. AB - We describe the first reported case of renal zygomycosis presenting as an isolated fungus ball (bezoar) without renal parenchymal invasion. Since all previous descriptions of renal involvement have discussed tissue invasion, our case is unique in that the infection was confined solely in the renal pelvis and extended to the distal ureter without signs of contiguous renal infection. Our patient later developed renal insufficiency while receiving amphotericin B Lipid Complex (ABLC). The therapy was changed to posaconazole with subsequent clinical, mycologic, and radiographic improvement and the patient has remained free of recurrence 5 years after diagnosis. PMID- 20353311 TI - New evidence of the involvement of Lichtheimia corymbifera in farmer's lung disease. AB - Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis resulting from recurrent exposure to moldy plant materials. We investigated and compared the initial response of respiratory epithelium after exposure to extracts of Sacharopolyspora rectivirgula, Lichtheimia corymbifera (formerly Absidia corymbifera), Eurotium amstelodami and Wallemia sebi. The two criteria for selection of these species were their high prevalence in the hay handled by FLD patients and the presence of high levels of specific precipitins to these molds in FLD patients’ sera. Hydrosoluble extracts were prepared from spores and hyphae grown in culture under optimal conditions for each of the four species. Confluent A549 cells were inoculated with one of the four calibrated soluble extracts. Two mediators, one inflammatory (Interleukin (IL)-8) and one allergic (IL-13), were quantified using real-time PCR and ELISA assay, after four exposure periods (30 min, 2 h, 4 h and 8 h). S. rectivirgula and L. corymbifera extracts were the only ones which induced a marked upregulation of IL-8, as shown by both real-time PCR and ELISA assay 8 h after the initial contact. This study adds to the growing body of evidence that L. corymbifera should be recognized as an etiologic agent of FLD along with S. rectivirgula. PMID- 20353312 TI - Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD. AB - OBJECTIVES: Treatment investigations with methylphenidate in adults with ADHD focus preferentially on the classical psychopathology: inattention, hyperactivity and impulsivity. ADHD-associated emotional symptoms, which are frequently present at least in ADHD subpopulations, were studied rarely. The vast majority of the placebo-controlled trials had observation periods between 4 and 8 weeks. To assess the medium- to long-term effects of extended release methylphenidate (MPH ER) on emotional symptoms and other psychopathology frequently seen in ADHD patients, we conducted a large-scale, multicenter treatment study. METHODS: We performed a randomised, 24-week, double-blind, placebo-controlled study in adults with ADHD. The diagnosis was made on the basis of the DSM-IV criteria, which were confirmed by clinical history and a structured psychopathological interview and the use of rating instruments. 363 patients were randomized to MPH-ER or placebo at a ratio of 2:1. The duration of the titration period was 5 weeks followed by a maintainance phase of 19 weeks. The efficacy measures were the observer rated 10 item Emotional Dysregulation Scale (EDS) derived from the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and a self-report, six-item Emotional Lability Scale (ELS) extracted from the long version of the Conners Adult ADHD Self Report Scale (CAARS:S:L). In addition we used the SCL-90-R for the assessment of ADHD associated and comorbid psychopathology. RESULTS: MPH-ER was statistically superior to placebo in reducing emotional symptoms as assessed by the EDS and the ELS. Obsessive-compulsive symptoms and those of problems with self-concept declined until the end of the observation period. The decline was more pronounced in MPH-ER treated individuals. The effects remained robust during the entire maintenance period until week 24. Symptoms of anxiety, depression, anger and hostility, phobia, paranoid ideations and psychoticism were not improved. CONCLUSIONS: MPH-ER appears to be an efficacious treatment for emotional symptoms with ADHD. Also obsessive-compulsive symptoms and problems with self-concept were affected positively. PMID- 20353313 TI - Bipolar disorder and comorbid attention deficit hyperactivity disorder. A distinct clinical phenotype? Clinical characteristics and temperamental traits. AB - OBJECTIVES: It has been suggested that bipolar disorder (BD) with comorbid ADHD represents a distinct clinical phenotype of BD. There are no data regarding potential heterogeneity between BD subjects with a diagnosis of ADHD in childhood whose ADHD remitted in adulthood (cADHD-BD) vs. BD patients with persistent ADHD diagnosis in adulthood (aADHD-BD). This heterogeneity may constitute a confounder in investigations of the nature of the co-occurrence between BD and ADHD. The aim of this paper is to compare BD patients without ADHD, to those with aADHD-BD, and those with cADHD-BD on clinical and temperamental characteristics, hypothesizing that maladaptive temperament will be increased in BD subjects with a stable diagnosis of ADHD in adulthood compared to those whose ADHD remitted. We further hypothesize that maladaptive temperament will be associated with the severity of both illnesses. METHODS: A total of 100 outpatients (aged 18-30 years) with BD in remission were included. The assessment of ADHD was made according to a procedure aimed to reduce potential recall biases. Subjects had to have a parent available and had never been treated with stimulants. Temperamental traits were assessed with the California Child Q-sort (CCQ) and the Early Adolescent Temperament Questionnaire (EATQ). RESULTS: Rate of co-occurrence of ADHD-BD was 18% lifetime and 10% current diagnosis. Patients with ADHD-BD (aADHD-BD+cADHD-BD) reported a significantly earlier onset of mood disorder, higher number of previous mood episodes, and significantly higher impulsivity than BD patients without ADHD. aADHD-BD showed a significantly earlier BD onset, higher number of previous mood episodes, higher impulsivity, decreased Reactive Control and higher Negative Emotionality temperamental scores than cADHD patients. CONCLUSION: Findings suggest that patients with aADHD-BD present a clinical phenotype distinct from that of patients with BD without ADHD or with a childhood ADHD diagnosis that remitted with the age. This appealing hypothesis of a BD-distinct phenotype that can be detected early due to its associated maladaptive temperamental traits requires further investigation in larger samples, supported by neuropsychological, genetic and imaging data. PMID- 20353314 TI - Reversible multifocal leukoencephalopathy associated with a nocturnal blood pressure non-dipper pattern. AB - The majority of cases of leukoencephalopathy related to hypertensive crisis show brain lesions predominantly in the posterior lobe. Such cases are usually classified as reversible posterior leukoencephalopathy syndrome (RPLS). A multifocal distribution pattern is also possible, but occurs seldom. Here we report two patients with extensive white matter lesions that affect the entire brain, related to hypertensive crisis associated with a non-dipper pattern of blood pressure during the night as well as renal dysfunction. This nocturnal blood pressure abnormality may be relevant for the distribution pattern of cerebral white matter lesions and underlines the concept that in these cases a 24 h ambulatory blood pressure monitoring is needed. PMID- 20353315 TI - Behavioural elements of professionalism: assessment of a fundamental concept in medical care. AB - BACKGROUND: The Nijmegen Professionalism Scale, an instrument for assessing professional behaviour of general practitioner (GP) trainees, consists of four domains: professional behaviour towards patients, other professionals, society and oneself. The purpose of the instrument is to provide formative feedback. AIM: The aim of this study was to examine the psychometric properties of the Nijmegen Professionalism Scale. METHODS: Both GP trainers and their GP trainees participated. Factor analysis was conducted for each domain. Factor structures of trainee and trainer groups were compared. Measure of congruence used was Tucker's phi. Cronbach's alpha was used to establish reliability. RESULTS: Factor structures of the instrument used by GP trainers and trainees were similar. Two factors for each domain were found: domain 1, Respecting patient's interests and Professional distance; domain 2, Collaboration skills and Management skills; domain 3, Responsibility and Quality management; and domain 4, Reflection and learning and Dealing with emotions. Congruence measures were substantial (>0.90). Reliability ranged from 0.78 to 0.95. CONCLUSION: This study to validate the instrument represents one further step. To construct a sound validity argument, a much broader range of evidence is required. Nevertheless, this study shows that the Nijmegen Professionalism Scale is a reliable tool for assessing professional behaviour. PMID- 20353316 TI - A randomized controlled trial of behavior change counseling education for medical students. AB - BACKGROUND: Educating medical students about how to effectively counsel patients with negative health behaviors (i.e., lack of exercise, smoking) is vitally important. Behavior change counseling is a promising method that can be used by physicians to encourage positive changes in health behaviors. PURPOSE: To examine the effectiveness of a 2 h workshop in behavior change counseling for medical students. METHODS: This study used a pre-post control group design with 35 second year medical students who were randomly assigned to participate in a behavior change counseling intervention or wait-list control group. Student knowledge and attitudes were assessed using multiple choice items and open-ended question prompts. Student skills were assessed via performance in a standardized patient encounter rated using the Behavior Change Counseling Index (BECCI). RESULTS: Student attitudes toward behavior change counseling were positive at both pre- and post-test assessment in both groups. Knowledge scores and BECCI total scores showed significantly greater improvement in the intervention group compared to the wait-list control group. CONCLUSIONS: This study found that a brief educational intervention had a positive impact on medical students' knowledge and skills in behavior change counseling, and that student attitudes about the counseling method were very positive. PMID- 20353317 TI - 'The Loss of My Elderly Patient:' Interactive reflective writing to support medical students' rites of passage. AB - BACKGROUND: The fostering of reflective capacity within medical education helps develop critical thinking and clinical reasoning skills and enhances professionalism. Use of reflective narratives to augment reflective practice instruction is well documented. AIM: At Warren Alpert Medical School of Brown University (Alpert Med), a narrative medicine curriculum innovation of students' reflective writing (field notes) with individualized feedback from an interdisciplinary faculty team (in pre-clinical years) has been implemented in a Doctoring course to cultivate reflective capacity, empathy, and humanism. Interactive reflective writing (student writer/faculty feedback provider dyad), we propose, can additionally support students with rites of passage at critical educational junctures. METHOD: At Alpert Med, we have devised a tool to guide faculty in crafting quality feedback, i.e. the Brown Educational Guide to Analysis of Narrative (BEGAN) which includes identifying students' salient quotes, utilizing reflection-inviting questions and close reading, highlighting derived lessons/key concepts, extracting clinical patterns, and providing concrete recommendations as relevant. RESULTS: We provide an example of a student's narrative describing an emotionally powerful and meaningful event - the loss of his first patient - and faculty responses using BEGAN. CONCLUSION: The provision of quality feedback to students' reflective writing - supported by BEGAN - can facilitate the transformation of student to professional through reflection within medical education. PMID- 20353318 TI - A remedial intervention linked to a formative assessment is effective in terms of improving student performance in subsequent degree examinations. AB - BACKGROUND: Intervention may help weaker medical students improve their performance. However, the effectiveness of remedial intervention is inconclusive due to small sample sizes in previous studies. We asked: is remedial intervention linked to a formative assessment effective in terms of improving student performance in subsequent degree examinations? METHODS: This was a retrospective, observational study of anonymous databases of student assessment outcomes. Data were analysed for students due to graduate in the years 2005-2009 (n = 909). Exam performance was compared for students who received remediation versus those who did not. The main outcome measure was summative degree examination marks. RESULTS: After adjusting for cohort, gender, overseas versus home funding, previous degree and previous performance in the corresponding baseline third year summative exam, students receiving a remedial intervention (after poor performance on a formative objective structured clinical examination and written exams mid-fourth year) were significantly more likely to obtain an improved mark on end-of-fourth year summative written (p = 0.005) and OSCE (p = 0.001) exams compared to those students who did not receive remediation. CONCLUSION: A remedial intervention linked to poor assessment performance predicted improved performance in later examination. There is a need for prospective studies in order to identify the effective components of remedial interventions. PMID- 20353319 TI - Patient-centred attitudes among medical students: gender and work experience in health care make a difference. AB - BACKGROUND: Previous studies of medical students' patient-centred attitudes show a decline across undergraduate education and overall higher scores for female students. AIM: To assess undergraduate students' patient-centred attitudes at various stages of education and to explore possible associations between attitudes and age, gender and work experience in health care. METHODS: In autumn 2005, medical students in Gothenburg (n = 797) were asked to answer Patient Practitioner Orientation Scale (PPOS), a validated instrument exploring attitudes towards the doctor-patient relationship. Data including gender, age, current term and students' work experience in health care were collected. RESULTS: Of 797 students 600 (75%) answered the questionnaire. No decrease of students' PPOS score across the curriculum was observed. PPOS scores from female students were higher compared to males (p < 0.0001) and female scores were significantly higher in the later terms compared with earlier (p = 0.0011). Female students had more experience from working in health care (p = 0.0023). Extended work experience was associated with higher PPOS only among females (p = 0.0031). CONCLUSION: No decline of students' patient-centred attitudes may indicate an ongoing shift. Gender differences in patient-centred attitudes were reproduced. Work experience in health care presents a new gender difference. These gender differences should be considered when training patient-centred attitudes and skills. PMID- 20353320 TI - Motivating medical students to learn teamwork skills. AB - BACKGROUND: This study examined teaching teamwork skills to first-year medical students. Teamwork skills focused on verbal communication in PBL-tutorial sessions and in healthcare teams. AIMS: The aim was to find out how to teach teamwork skills to first-year medical students and how to motivate them to learn these skills. METHOD: Three consecutive classes of first-year medical students (N = 342) participated in teamwork skills module in the years 2006, 2007 and 2008. After the first year, the introduction to the topic was revised in order to be more motivating to medical students. After each module data were collected with a feedback questionnaire containing numerical and open questions. By analyzing the students' numerical answers and the content of students' open answers regarding the module, we examined how the revised introduction affected students' perceptions of the usefulness of the module. RESULTS: Medical students' feedback in the years 1 (n = 81), 2 (n = 99) and 3 (n = 95) showed that the students found the module in the second and third years significantly more useful than in the first year. These results support earlier findings that clearly stated clinical relevance motivates medical students. CONCLUSIONS: When introducing multidisciplinary subjects to medical students, it is important to think through the clinical relevance of the topic and how it is introduced to medical students. PMID- 20353321 TI - The Bologna Process - From futility to utility. PMID- 20353322 TI - A chance too good to miss. PMID- 20353323 TI - Research in medical education: doctoral dissertation reports. PMID- 20353324 TI - Undergraduate medical education in the Gulf Cooperation Council: a multi countries study (Part 2). AB - BACKGROUND: The Gulf Cooperation Council (GCC) countries have witnessed over the last 40 years a rapid and major social, cultural, and economic transformation. The development of medical education in the region is relatively new, dating from the late 1960s. An important goal among the medical colleges in the region is to graduate national physicians who can populate the healthcare service of each country. AIM: The aim of this study is to provide understanding of undergraduate medical education in each of the six GCC countries and the challenges that each face. METHODS: This is a descriptive cross-sectional study. Fourteen senior medical faculty were requested to submit information about undergraduate medical education in their own countries, focusing on its historical background, student selection, curriculum, faculty, and challenges. RESULTS: The information provided was about 27 medical colleges: 16 from the Kingdom of Saudi Arabia (KSA), five from the United Arab Emirates, two from the Kingdom of Bahrain, two from Sultanate of Oman, one from Kuwait and one from the State of Qatar. It was found that older colleges are reviewing their curriculum while new colleges are developing their programs following current trends in medical education particularly problem-based learning and integrated curricula. The programs as described 'on paper' look good but what needs to be evaluated is the curriculum 'in action'. Faculty development in medical education is taking place in most of the region's medical colleges. CONCLUSION: The challenges reported were mainly related to shortages of faculty, availability of clinical training facilities, and the need to more integration with the National Health Care services. Attention to quality, standards, and accreditation is considered essential by all colleges. PMID- 20353325 TI - Twelve tips for evaluating educational programs. AB - At one time or another, nearly all educators will need to evaluate an educational program to determine its merit or worth. These tips will help readers collect information to inform a meaningful evaluation, whether for local use or broad dissemination (i.e., research). The two most important questions in any evaluation are, 'Whose opinion matters?' and 'What would really be meaningful to them?' Other key steps include getting input from others, focusing on desired outcomes before selecting instruments, considering the validity or trustworthiness of the data, and pilot testing the evaluation process. PMID- 20353326 TI - The Bologna Process and its implications for medical education. PMID- 20353327 TI - The Bologna Process - A global vision for the future of medical education. AB - What has become known as the Bologna Process has evolved over a series of ministerial conferences with the last meeting in Leuven and Louvain-la-Neuve in 2009. There has been a move towards recognition of the benefits to be gained from greater transparency, a general recognition of degrees across Europe, cooperation with regard to quality assurance, an emphasis on more flexible learning paths and lifelong learning, and the promotion of mobility. This paper highlights the ambitious objectives underpinning the Bologna Declaration and Process and the developments since the 1999 Declaration and the current position in particular with regard to medicine. The paper describes common myths and misunderstandings about the Process relating to the two cycle model, the progress of students after the first cycle and the concept of harmonisation rather than uniformity. It is argued that the Bologna Process can serve as a catalyst for the necessary change in medical education. With careful management and imaginative implementation and the necessary vision, creativity and enthusiasm, any problems can be circumnavigated and rich rewards achieved. The Bologna Process is constantly evolving and its dynamic nature is one of its strengths. Medicine has much to contribute and should be part of this Process. PMID- 20353328 TI - The Bologna process, medical education and integrated learning. AB - The Bologna Declaration, signed in 1999 by all European Ministers of Education and currently in a phase of active implementation in Europe, specifies a three cycle degree structure - Bachelor's, Master's, Doctorate - for all disciplines in Higher Education. The application of this model to medical education has been opposed on various grounds. In particular, a 'Ba/Ma' model for undergraduate medical degrees has been viewed as undoing recent progress towards fully integrated learning of basic and clinical medical sciences. However, this can be overcome by the use of a learning outcomes framework, agreed at European level, that reinforces the primarily medical nature of both degrees and which requires integrated teaching, learning and assessment at every stage. With this proviso, application of the Bologna principles to medicine can help to drive educational development and quality enhancement in European medical education. PMID- 20353329 TI - Reports of PhD studies selected for presentation at the AMEE 2009 conference in Malaga, Spain, 29 August to 2 September. PMID- 20353330 TI - Student and teaching characteristics related to ratings of instruction in medical sciences graduate programs. AB - BACKGROUND: Although the validity of students' ratings of instruction has been documented, several student and course characteristics may be related to the ratings students give their instructors. AIMS: The purpose of this study was to examine student ratings obtained from the Universal Student Ratings of Instruction (USRI) instrument. These responses were compared to various student characteristics. Also, teaching characteristics that were most closely associated with the ratings were determined. METHOD: A total of 1738 USRI forms were completed by graduate students enrolled in medical science courses from 1999 to 2006 in the Faculty of Medicine at a Canadian university. RESULTS: Between group comparisons showed that negative student perceptions about the course (i.e., did not have the freedom to select), perceiving the course workload as high, and low grade expectations held were related to negative student ratings of overall quality of instruction. In terms of the student and teaching characteristics, organization of course material and perceptions of whether students felt they learned a lot in the course were most closely related to global ratings of instructional quality. CONCLUSION: Implications for teaching focus on improving the organization and delivery of course content that meets the learning objectives of graduate students in medical sciences. PMID- 20353331 TI - Medical students' clinical performance in general practice - Triangulating assessments from patients, teachers and students. AB - BACKGROUND: Formative assessment of medical students' clinical performance during general practice clerkship is necessary to learn consultation skills. AIMS: Our aim was to triangulate feedback using patient questionnaires, written self assessment and teachers' observation-based assessment, and to describe the content of this feedback. METHOD: We developed StudentPEP, a 15-item version of EUROPEP, a tool for measuring patients' evaluation of quality in general practice. The teacher and student forms consisted of five StudentPEP-items and open-ended questions asking for approval and improvement needed on four aspects. Quantitative scores were analyzed statistically. Free-text comments were analyzed and categorized into 'specific and concrete' versus 'general and unspecific'. RESULTS: One hundred seventy-three students returned data from 2643 consultations. Mean patients' scores for 15 items were 4.3-4.8 on a five-point Likert scale. Mean teacher scores were 4.4 on five items, while students' mean self-assessments were 3.6-3.8. In an analysis of 380 consultations, students were more specific and concrete in their self-evaluation compared with teachers (p < 0.01). CONCLUSION: Patients scored students' performance high compared with students' self-assessments. Teachers' scores were in accordance with patients' scores. Teachers' written evaluations of students were often general. There is a potential for improving teachers' feedback in terms of more specific and concrete comments. PMID- 20353332 TI - AMEE 2009 spotlight on educational research. AB - The AMEE meeting is unique among the medical education conferences in that it is truly international. Educational research presented at the 2009 AMEE Meeting was both diverse and robust. In this article, we will present an overview of educational research from the meeting. We will begin with outlining our methods for the selection and categorization of themes, discuss some highpoints from some of the respective themes, and finally from the conference overall. PMID- 20353333 TI - Finnish medical students'perceptions of Theatre in Education method in learning interpersonal communication competence. PMID- 20353334 TI - eMedical Teacher. PMID- 20353336 TI - (99m)Tc Auger electrons for targeted tumour therapy: a review. AB - PURPOSE: Targeted radiotherapy using Auger electrons presents multiple advantages and challenges. The advantageous characteristics of this type of radiotherapy can explain the growing interest in these specific electrons for cancer therapy. During the last decade, Technetium-99m ((99m)Tc) has been used as an imaging agent and only recently has it been analysed as a potential therapeutic agent. This paper aims to be a review on the potential use of (99m)Tc as a therapeutic agent. CONCLUSIONS: The physical properties of (99m)Tc along with its large availability through a generator in situ may represent a new and important pathway in targeted radiotherapy. Experimental data obtained so far has encouraged multiple researchers to investigate (99m)Tc further as a therapeutic agent for multiple common oncologic situations. In spite of these initial attempts to use (99m)Tc as a therapeutic agent beyond that of imaging, future studies are required to better define its dosimetric implications and radiobiological efficacy. PMID- 20353337 TI - Delayed chromosomal instability in lymphocytes of cancer patients after radiotherapy. AB - PURPOSE: To assess possible delayed chromosomal instability (DCI) expressed as elevated chromatid breakage in cells containing previously formed chromosome type aberrations in cultured blood lymphocytes of cancer patients after radiotherapy (RT). MATERIALS AND METHODS: Twenty patients treated for uterine cancer with external Co(60) RT, without chemotherapy, were selected. Blood was taken before, 1-2 days after RT and one year later. Lymphocytes were cultured for 50 and 100 h. Metaphases were stained with fluorescence-plus-Giemsa and analysed for chromosome and chromatid aberrations in 1st (M1) and 3rd plus later (M3+) mitoses. RESULTS: RT caused a significant increase of radiation-specific chromosome aberrations in patients' lymphocytes together with DCI, which was observed as an excessive yield of cells containing both chromosome and chromatid aberrations (defined as C(acs&act)). This DCI passed successfully through mitoses in vitro, and at the end of RT a mean yield of 'extra' C(acs&act) was 3 x 10(-3) x cell(-1) amongst either M1 or M3+ cells. At the end of RT and one year later DCI in M1 lymphocytes appeared at random amongst patients, but some inter-individual variation was found for DCI presence in M3+ cells at both post-irradiation samplings. As time passed, the mean yield of lymphocytes exhibiting DCI decreased in vivo and one year after RT reached the pre-treatment level of 1 x 10(-3) x cell(-1). CONCLUSIONS: DCI was demonstrated in descendants of human lymphocytes after therapeutic irradiation. The effect diminished one year later, suggesting that the progeny of patients' irradiated stem cells did not produce new daughter lymphocytes exhibiting DCI during the studied post-irradiation period. PMID- 20353338 TI - Histamine protects bone marrow against cellular damage induced by ionising radiation. AB - PURPOSE: Based on our previous data on the histamine radioprotective effect on small intestine, in the present work we aimed to determine whether histamine is able to protect bone marrow cells against ionising radiation damage. MATERIALS AND METHODS: 56 mice and 40 rats were divided into four groups. Histamine and histamine-irradiated groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose on whole-body using Cesium-137 source and were sacrificed three days after irradiation. We evaluated the number of medullar components, bone marrow trophism, oedema, vascular damage, and other histological characteristics and also proliferation markers by immunohistochemistry. RESULTS: Histamine treatment substantially reduced the grade of aplasia, the oedema and vascular damage induced by ionising radiation on bone marrow of mice and rats. Additionally, histamine preserved medullar components increasing the number of megakaryocytes (14.0 +/- 1.0 vs. 7.3 +/- 1.0 in mice; and 9.9 +/- 1.3 vs. 4.1 +/- 1.0 in rats, P < 0.01) and also myeloid (253.4 +/- 37.6 vs. 7.8 +/- 1.5 in mice; and 52.0 +/- 3.7 vs. 31.8 +/- 3.1 in rats, P < 0.01), lymphoid (97.4 +/- 6.5 vs. 19.8 +/- 1.6 in mice; and 23.4 +/- 0.9 vs. 11.7 +/- 2.5 in rats, P < 0.01) and erythroid cells (165.0 +/- 9.1 vs. 8.8 +/- 2.8 in mice; and 27.3 +/- 2.3 vs. 15.6 +/- 3.5 in rats, P < 0.01) per mm(2). This effect was associated with an increased proliferation rate of bone marrow cells. CONCLUSIONS: Histamine reduces ionising radiation toxicity on bone marrow cells being a suitable candidate for use as radioprotector, especially for patients undergoing radiotherapy who are at the risk of bone marrow or small intestine damage. PMID- 20353339 TI - Protein kinase C-dependent inhibition of BK(Ca) current in rat aorta smooth muscle cells following gamma-irradiation. AB - PURPOSE: The aim of this study was to estimate the effects of non-fatal whole body gamma-irradiation on outward potassium plasma membrane conductivity in rat vascular smooth muscle cells (VSMC), and to identify underlying mechanisms. MATERIALS AND METHODS: Rats were exposed to a 6 Gy dose irradiation from a cobalt(60) source. Whole-cell potassium current was measured in freshly isolated rat aorta smooth muscle cells using standard patch-clamp technique. RESULTS: We have determined that whole-body ionising irradiation significantly inhibits whole cell outward K(+) current in rat aortic VSMC obtained from irradiated rats 9 and 30 days after irradiation, and this inhibition appears to be increased throughout post-irradiation period. Using selective inhibitors of small conductance Ca(2+) activated K(+) channels (SK(Ca)), apamin (1 microM), intermediate conductance Ca(2+)-activated K(+) channels (IK(Ca,)), charybdotoxin (1 microM) and a large conductance Ca(2+)-activated K(+) channels (BK(Ca)), paxilline (500 nM), we established that the main component of whole-cell outward K(+) current in rat aortic VSMC is due to BK(Ca). It is clear that on the 9th day after irradiation paxilline had only a small effect on whole-cell outward K(+) current in VSMC, and was without effect on the 30th day post-irradiation, suggesting complete suppression of the BK(Ca) current. The PKC inhibitor, chelerythrine (100 nM), effectively reversed the suppression of whole-cell outward K(+) current induced by ionising irradiation in the post-irradiation period of 9 and 30 days. CONCLUSIONS: The results suggest that irradiation-evoked inhibition of the BK(Ca) current in aortic VSMC is mediated by PKC. Taken together, our data indicate that one of the mechanisms leading to elevation of vascular tone and related arterial hypertension development under ionising irradiation impact is a PKC-mediated inhibition of BK(Ca) channels in VSMC. PMID- 20353340 TI - Relative toxicity of (45)Ca beta-particles and (242)Cm alpha-particles following their intravenous injection into mice as radiolabelled FAP. AB - PURPOSE: To determine the relative toxicity of alpha- and beta-radiations under conditions of controlled temporal and spatial dose distribution. METHODS: Fused aluminosilicate particles were radiolabelled with either (45)Ca (a beta-emitter) or (242)Cm (an alpha-emitter). These were injected into CBA/Ca mice to give lifespan, whole-body doses of approximately 0.5, 1.0 or 1.5 Gy. Most animals were entered into a lifespan toxicity study, but some were killed for radiochemical analysis and autoradiography. RESULTS: Twenty-seven tumour types were identified. The most common malignant tumours were: Mammary carcinoma; liver carcinoma; malignant lymphoma; uterine histiocytic sarcoma. Excess relative risk (strictly hazard ratio) was higher for radiation-induced carcinomas than for sarcomas. The carcinomas, but not sarcomas showed a reduction in relative risk at the highest radiation dose employed. This reduction was most easily attributed to a systemic effect. The highest relative toxicity measured was for liver carcinoma (5.9, 95% confidence intervals [CI] 2.4, 14) and the lowest for uterine carcinoma (0.6, CI 0.03, 9.7). Overall, the excess relative risk ratio for SURVIVAL WAS 1.9 (CI 1.1, 3.2), FOR ALL CARCINOMA WAS 2.3 (CI 1.7, 3.0) AND FOR ALL SARCOMA WAS 2.7 (CI 0.72, 10). CONCLUSIONS: The 10-fold variability in the observed toxicity ratio for different tumour endpoints shows that tissue sensitivity is a more important determinant of relative toxicity than radiation quality. The use of single radiation-weighting (w(R)) factors for radiation risk prediction and for radiological protection dosimetry is inconsistent with scientific observation. PMID- 20353341 TI - High-throughput antibody-based assays to identify and quantify radiation responsive protein biomarkers. AB - PURPOSE: After a radiological 'dirty bomb' incident in a major metropolitan center, substantial numbers of people may be exposed to radiation. However, only a fraction of those individuals will need urgent medical attention. Consequently, a rapid screening test is needed to identify those people who require immediate treatment. MATERIAL AND METHODS: Ten normal human cell lines were screened by enzyme-linked immunosorbent assay (ELISA) for the expression of a dozen secreted cytokines that have been reported to have changes in protein or mRNA levels at 1, 2, and 3 days after 0-10 Gy irradiation using (137)Cs gamma rays at 0.82 Gy min( 1). After this systematic in vitro screen, we measured changes in the level of a subset of these candidate proteins in plasma from irradiated C57BL/6 mice (n = 3 per group), comparing shams with a single radiation dose (5 Gy X-rays) at 3.7 Gy min(-1) at 6 h after irradiation. RESULTS: We identified four cytokine molecules that had altered levels after radiation exposure, one of which, Interleukin (IL) 6, was consistently elevated after irradiation in vitro and in vivo. CONCLUSIONS: Our findings underscore the potential for IL6 as a marker for an immunoassay based, rapid, high-throughput biodosimeter. PMID- 20353342 TI - Low-dose radiation-induced hormetic effect on hematopoietic reconstitution. AB - PURPOSE: To investigate the effects on hematopoietic reconstitution of recipient mice receiving bone marrow cells (BMC) of donor pre-exposed to low-dose radiation (LDR). MATERIALS AND METHODS: BMC were irradiated in vitro at various low-dose X rays radiation. Tritiated thymidine ((3)H-TdR) incorporation was adopted to measure the proliferation of the BMC in vitro, and then the optimal radiation doses were selected for further study in vivo. Irradiated recipient mice (7.5 Gy) were infused by BMC exposed to 6 and 8 cGy. The counts of recipients' peripheral blood cells (PBC) and bone marrow mononuclear cells (BMMNC) were monitored at the 5th, 10th, 15th, and 30th day after BMC infusion. The colony-forming units in the recipient spleens (CFU-S) were calculated at the 10th day after infusion. RESULTS: Exposed to 6 and 8 cGy, BMC demonstrated significant proliferative activities in vitro. When the recipient mice receiving BMC pre-exposed to low dose radiation (6 and 8 cGy), the counts of white blood cell (WBC), BMMNC and CFU S were consistently higher than those in control. CONCLUSIONS: BMC of donor irradiated by LDR in vitro may facilitate the hematopoietic reconstitution of the recipient mice. PMID- 20353343 TI - Mutagenic response of 2.45 GHz radiation exposure on rat brain. AB - PURPOSE: To investigate the effect of 2.45 GHz microwave radiation on rat brain of male wistar strain. MATERIAL AND METHODS: Male rats of wistar strain (35 days old with 130 +/- 10 g body weight) were selected for this study. Animals were divided into two groups: Sham exposed and experimental. Animals were exposed for 2 h a day for 35 days to 2.45 GHz frequency at 0.34 mW/cm(2) power density. The whole body specific absorption rate (SAR) was estimated to be 0.11 W/Kg. Exposure took place in a ventilated Plexiglas cage and kept in anechoic chamber in a far field configuration from the horn antenna. After the completion of exposure period, rats were sacrificed and the whole brain tissue was dissected and used for study of double strand DNA (Deoxyribonucleic acid) breaks by micro gel electrophoresis and the statistical analysis was carried out using comet assay (IV-2 version software). Thereafter, antioxidant enzymes and histone kinase estimation was also performed. RESULTS: A significant increase was observed in comet head (P < 0.002), tail length (P < 0.0002) and in tail movement (P < 0.0001) in exposed brain cells. An analysis of antioxidant enzymes glutathione peroxidase (P < 0.005), and superoxide dismutase (P < 0.006) showed a decrease while an increase in catalase (P < 0.006) was observed. A significant decrease (P < 0.023) in histone kinase was also recorded in the exposed group as compared to the control (sham-exposed) ones. One-way analysis of variance (ANOVA) method was adopted for statistical analysis. CONCLUSION: The study concludes that the chronic exposure to these radiations may cause significant damage to brain, which may be an indication of possible tumour promotion (Behari and Paulraj 2007). PMID- 20353344 TI - Design, synthesis and anticholinesterase activity of some new alpha aminobisphosphonates. AB - Some new alpha-aminomethylenephosphonic acids 1-11 were synthesised and characterised by (1)H, (13)C, (31)P NMR, IR spectroscopy and elemental analysis. The potencies of these compounds to inhibit human erythrocyte acetylcholinesterase (hAChE, EC 3.1.1.7) were studied by a modified Ellman's method. In addition, the log P values were computed by Hyperchem software. Here, alendronate was used as a reference inhibitor. Results showed that the IC(50) values ranged from 9.11 to 28.72 mM. The half maximal inhibitory concentration (IC(50)) value decreased with an increasing number of carbon atoms of the amine group in compounds 1-5. Also, in most cases, increasing the number of carbon atoms led to enhancement of the toxicity as predicted by the log P values. Using Lineweaver-Burk and Dixon analysis, it was indicated that compounds 1-10 are mixed inhibitors while compound 11 is a coupling or uncompetitive inhibitor. The results showed that the electronic changes have ignorable effects, steric influence is important in some cases, but the lipophilicity parameter is the most significant factor in hAChE inhibition by bisphosphonates. PMID- 20353345 TI - Role of E-cadherin in epithelial architecture maintenance. AB - Morphogenesis and architecture of a developing epithelium is controlled by both cell shape and contacts, mediated by spatially and temporally regulated cell adhesion molecules. The authors study if E-cadherin functions as a key factor of epithelial adhesion and epidermal architecture in vivo. They apply whole-mount digital deconvolution microscopy to evaluate three-dimensional (3D) E-cadherin expression during skin morphogenesis of Rhinella arenarum and in a cell adhesion alteration model. Results show morphogenetic changes in the 3D E-cadherin spatiotemporal expression pattern correlated with the increase of E-cadherin and in the number of cells with hexagonal geometry. Alterations in junction-protein phosphorylation showed drastic loss of E-cadherin and beta-catenin in cell-cell contacts and the increase of cytoplasm and nuclear beta-catenin in epidermis, suggesting the activation of the beta-catenin signal pathway. Surprisingly, no changes in cell shape and skin architecture were registered, suggesting that epidermal E-cadherin appears to be involved in signaling rather than cell contact maintenance in vivo. PMID- 20353346 TI - Two new alpha1-globin gene point mutations: Hb Nedlands (HBA1:c.86C>T) [alpha28(B9)Ala-->Val] and Hb Queens Park (HBA1:c.98T>A) [alpha32(B13)Met-->Lys]. AB - We report two new point mutations of the alpha1-globin gene found in a Greek and a Burmese patient, both living in Western Australia. The patients were initially selected for their microcytic hypochromic parameters as belonging to a group suspected for uncommon (deletion) defects. Gap-polymerase chain reaction (gap PCR) and multiplex ligation-dependent probe amplification (MLPA) technologies were applied, and in those cases not showing deletions, direct sequencing was performed. We have found 1) HBA1:c.86C>T, Hb Nedlands [alpha28(B9)Ala-->Val] which, based on the red cell indices and phenotype prediction scores, is presumed to be clinically silent, and 2) HBA1:c.98T>A, Hb Queens Park [alpha32(B13)Met- >Lys] which seems to be associated with a mild alpha-thalassemia (alpha-thal) phenotype. The phenotype/genotype correlation is briefly described. PMID- 20353347 TI - Extended molecular spectrum of beta- and alpha-thalassemia in Oman. AB - Sickle cell disease is known to be very common in the Omani population, although data are limited concerning beta-thalassemia (beta-thal). We report the molecular background of 87 unrelated patients from the Sultanate of Oman, diagnosed with beta-thal major (beta-TM), beta-thal intermedia (beta-TI) or minor. Diagnosis was based on clinical and hematological data and confirmed by molecular analysis. We found 11 different beta-thal determinants in our cohort, which consists of subjects from different regions of Oman. Six of these mutations have not been previously reported in the Omani population. The prevalence of alpha-thal single gene deletions (-alpha(3.7) and -alpha(4.2)) in the same cohort was very high (58.3%). These data will contribute to the implementation of a country-wide service for early molecular detection of hemoglobinopathies and for providing genetic counseling following premarital screening. PMID- 20353348 TI - Forecasting hemoglobinopathy burden through neonatal screening in Omani neonates. AB - To evaluate the incidence of hemoglobinopathies in Omani subjects and to forecast its future burden on health resources, we initiated a prospective neonatal screening program in two major cities of the Sultanate of Oman. Consecutive cord blood samples from a total of 7,837 neonates were analyzed for complete blood counts and for hemoglobin (Hb) profile by high performance liquid chromatography (HPLC). No case with Hb H (beta4) was detected. We observed that the overall incidence of alpha-thalassemia (alpha-thal) was 48.5% [based on the presence of Hb Bart's (gamma4)] and the beta-globin-related abnormalities accounted for 9.5% of the samples (4.8% sickle cell trait, 2.6% beta-thal trait, 0.9% Hb E trait, 0.8% Hb D trait, 0.08% Hb C trait, 0.3% sickle cell disease and 0.08% homozygous beta-thal). This is also the first large study to establish reference ranges of cord red blood cell (RBC) indices for Omani neonates. PMID- 20353349 TI - alpha-Thalassemia-like globin gene expression by primitive erythrocytes derived from human embryonic stem cells. AB - Under culture conditions that promote hematopoietic differentiation, human embryonic stem cells (huESC) give rise to primitive erythroid cells that closely resemble the nucleated erythrocytes of early-stage human embryos. The globin chain distribution of these cells is similar to that seen during the embryonic and fetal stages of development. Here we show that huESC-derived erythroid cells produce substantial quantities of homotetrameric hemoglobin (Hb) composed exclusively of gamma-globin-containing subunits. The globin synthesis of these erythroid cells was also significantly unbalanced, with a substantial decrease of alpha-like globin chain synthesis in relation to that of their beta-like globins, a pattern characteristically associated with alpha-thalassemia (alpha-thal). This pattern of unbalanced globin synthesis appears to be an inherent feature of human erythroid cells that synthesize predominantly embryonic-stage globins. PMID- 20353350 TI - Relationship between impaired glycation and the N-terminal structure of the Hb Gorwihl [beta5(A2)Pro-->Ala] variant. AB - We studied the structural environment surrounding the beta-N-terminal glycation site of a hemoglobin (Hb) molecule in which the proline residue at beta5(A2) was substituted by alanine in silico. By computer analysis that used Protein Data Bank data (PDB ID: 1BZ0), we tried to clarify the reason for impaired glycation of Hb Gorwihl [beta5(A2)Pro-->Ala]. On the basis of the results, we predicted that the glycation site would have the following characteristics: 1) glycation of the beta-N-terminus of Hb is probably accelerated by the neighboring histidine residue at beta2(NA2), which acts as an acid-base catalyst via a phosphate mediated proton transfer; and 2) the mutation beta5(A2)Pro-->Ala would bring about impaired glycation of the N-terminal residue by forming an electrostatic bond between the alpha amino group of beta1(NA1)Val and beta carboxyl group of beta79(EF3)Asp. PMID- 20353351 TI - Hb Perpignan [beta136(H14)Gly-->Ser], a silent variant associated with normal hematology. AB - A second case of Hb Perpignan [beta136(H14)Gly-->Ser] was identified in a Burmese woman living in New Zealand. Although previously detected in France, this is the first formal description of the variant, which is electrophoretically silent and hematologically normal. This presentation as a benign substitution is in keeping with the low level of phylogenetic conservation of the H14 glycine. PMID- 20353352 TI - Hb Tak and Hb Q-Thailand in Thai patients are S-window hemoglobin variants revealed by high performance liquid chromatography. AB - The S-window hemoglobin (Hb) variants revealed by high performance liquid chromatography (HPLC) were studied in 12 Thai individuals. The variants were identified, using DNA sequencing and multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), to be six cases of Hb Tak [beta147 (+AC)], and six cases of Hb Q-Thailand [alpha74(EF3)Asp-->His], respectively. By using the Capillarys 2-capillary zone electrophoresis (CE), Hb Tak and Hb Q Thailand co-migrated with Hb F in zone 7. This might pose a problem as the high Hb F conditions suggest a differential diagnosis. The S-window Hb variants are mostly Hb Tak and Hb Q-Thailand in the Thai population rather than Hb S [beta6(A3)Glu-->Val]. The definite identification of Hb variants detected by HPLC or capillary electrophoresis (CE) requires DNA analysis. PMID- 20353353 TI - Compound heterozygous Hb Tak/Hb E causes secondary erythrocytosis in a Thai family. AB - Hb Tak is a rare cause of secondary erythrocytosis. It results from the insertion of two nucleotides (AC) at the termination codon between codon 146 and codon 147 of the beta-globin gene. This insertion causes a frameshift in the terminating codon 147 resulting in an elongated beta chain with an impaired formation of the T-state. We report a Thai family with a compound heterozygosity for Hb Tak [beta147 (+ AC)] and Hb E [beta26(B8)Glu-->Lys] which displayed an asymptomatic erythrocytosis. PMID- 20353354 TI - Hb Valletta [beta87(F3)Thr-->Pro] and Hb Marseille/Long Island [beta2(NA2)His- >Pro; (-1)Met-(+1)Val-(+2)Pro-Leu], in a unique compound heterozygote with a normal hemoglobin phenotype. AB - This study refers to the quantitative hemoglobin (Hb) phenotype of a 19-year-old female with Hb Valletta [beta87(F3)Thr-->Pro] in association with Hb Marseille/Long Island [beta2(NA2)His-->Pro; (-1)Met-(+1)Val-(+2)Pro-Leu] and a normal Hb electrophoretogram. The data serve to alert investigators to the possibility that relatives with apparently normal Hb phenotypes may be transmitting mutant alleles and suggest methods for identification. PMID- 20353355 TI - Detection of Hb Constant Spring by a capillary electrophoresis method. AB - Hb Constant Spring [Hb CS; alpha142, Term-->Gln (TAA>CAA in alpha2)] is the most prevalent nondeletional alpha-thalassemia (alpha-thal) anomaly in southern China. In conjunction with alpha(0)-thal, it can cause severe Hb H (beta(4)) disease. The present study was done to evaluate the efficiency of two diagnostic methods in detecting Hb CS. Automated high performance liquid chromatography (HPLC) and Sebia Capillarys 2, a capillary electrophoresis method, were applied to blood samples from 21 individuals with Hb CS trait. Of the 21 cases, all (100%) were detected by capillary electrophoresis, whereas only 16 (76.2%) were detected by HPLC. We concluded that the Sebia Capillarys 2 is the preferred method for Hb CS screening. PMID- 20353356 TI - Molecular characterization of a Chinese pedigree with beta-thalassemia intermedia. AB - Hereditary persistence of fetal hemoglobin (HPFH), often associated with mutations in the beta-globin gene cluster, is normally benign, but a person carrying both HPFH and another beta-thalassemia (beta-thal) mutation will develop serious anemia. These people might be erroneously diagnosed as having homozygous beta-thal with common reverse dot-blot methods. Here we report a 5-year old boy with thalassemia intermedia, who is a compound heterozygote for the rare HPFH-6 deletion with codons 41/42 (-TCTT) beta(0)-thal, who inherited the deletion from his mother and the beta(41/42) mutation from his father. PMID- 20353357 TI - A rapid single-tube multiplex polymerase chain reaction assay for the seven most prevalent alpha-thalassemia deletions and alphaalphaalpha(anti 3.7) alpha-globin gene triplication. AB - alpha-Globin gene triplications may exacerbate the alpha chain and beta chain imbalance in beta-thalassemia (beta-thal) and may compensate for the effect of alpha-globin gene deletion in alpha-thal. Identification of an alpha-globin gene triplication is, therefore, valuable in predicting the clinical phenotype of the thalassemias. To be able to detect alpha-globin gene triplications, we have modified an existing multiplex polymerase chain reaction (PCR) assay for the seven most prevalent alpha-globin gene deletions by incorporating two triplication-specific primers and concurrently substituting one of the original primers by a newly designed primer. This modified multiplex PCR assay was evaluated by performing the assay on archival DNA samples and on peripheral blood samples from 163 suspected thalassemia cases. It was found to function properly. Our assay thereby represents the first multiplex PCR assay that can detect both the seven most prevalent alpha-globin gene deletions and the alphaalphaalpha(anti 3.7) alpha-globin gene triplication in a single-tube reaction. PMID- 20353359 TI - beta-Globin gene cluster haplotypes of Hb D-Punjab. PMID- 20353358 TI - Misdiagnosis of a beta-thalassemia heterozygote using a reverse dot-blot method may be caused by a polymorphic locus in the wild type sequence of the beta-globin gene. AB - Reverse dot-blot is an effective method for detecting beta-thalassemia (beta thal) mutations. In this study, we report the cause of a misdiagnosis by reverse dot-blot. One patient with a beta-globin genotype that was initially diagnosed as a codon 17 (A>T) homozygote by reverse dot-blot at our Clinic, was later shown to be a codon 17 (A>T) heterozygote by direct sequencing of the amplified fragment and by sequence analysis of a recombinant T vector plasmid containing an amplified fragment of the beta-globin gene. A polymorphic locus around the mutation site within the haploid DNA that lacked the codon 17 mutation was identified. This result suggests that when reverse dot-blot is used for the genetic diagnosis of beta-globin, polymorphic loci around the mutation site should be taken into consideration, and more allele specific oligonucleotide probes should be designed according to the polymorphic loci. PMID- 20353360 TI - Evaluation of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for reporting methicillin-resistant Staphylococcus aureus infections at a hospital in Illinois. AB - BACKGROUND: States, including Illinois, have passed legislation mandating the use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for reporting healthcare-associated infections, such as methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: To evaluate the sensitivity of ICD-9-CM code combinations for detection of MRSA infection and to understand implications for reporting. METHODS: We reviewed discharge and microbiology databases from July through August of 2005, 2006, and 2007 for ICD-9-CM codes or microbiology results suggesting MRSA infection at a tertiary care hospital near Chicago, Illinois. Medical records were reviewed to confirm MRSA infection. Time from admission to first positive MRSA culture result was evaluated to identify hospital-onset MRSA (HO-MRSA) infections. The sensitivity of MRSA code combinations for detecting confirmed MRSA infections was calculated using all codes present in the discharge record (up to 15); the effect of reviewing only 9 diagnosis codes, the number reported to the Centers for Medicare and Medicaid Services, was also evaluated. The sensitivity of the combination of diagnosis codes for detection of HO-MRSA infections was compared with that for community-onset MRSA (CO-MRSA) infections. RESULTS: We identified 571 potential MRSA infections with the use of screening criteria; 403 (71%) were confirmed MRSA infections, of which 61 (15%) were classified as HO-MRSA. The sensitivity of MRSA code combinations was 59% for all confirmed MRSA infections when 15 diagnoses were reviewed compared with 31% if only 9 diagnoses were reviewed (P < .001). The sensitivity of code combinations was 33% for HO-MRSA infections compared with 62% for CO-MRSA infections (P < .001). CONCLUSIONS: Limiting analysis to 9 diagnosis codes resulted in low sensitivity. Furthermore, code combinations were better at revealing CO-MRSA infections than HO-MRSA infections. These limitations could compromise the validity of ICD-9-CM codes for interfacility comparisons and for reporting of healthcare-associated MRSA infections. PMID- 20353361 TI - Quantifying established clinical assessment measures using 3D-movement analysis in individuals with Down syndrome. AB - PURPOSE: A movement protocol for quantifying functional limitation in people with Down syndrome (DS) during the execution of a series of range of motion (ROM) tasks has been developed as a new assessment approach, combining quantitative measures of movement analysis and functional mobility with clinically established qualitative motor skill assessments. METHODS: Fifteen subjects with DS and 11 subjects with typical development were evaluated using this movement protocol. RESULTS: The results revealed longer durations in execution across all tasks in the DS group and were most likely due to low muscular tone and poor coordination. A significant difference in ankle ROM was found in the DS group during leg lifting, with a wide plantar-flexion demonstrated during the entire movement. This result may be associated with the typical strategy for foot contact that generally favours the toe. Significant differences were also found in the trunk ROM and in the knee ROM and may likely reflect an increase of agonist-antagonist co-contraction, a strategy that may modify stability and dynamic equilibrium. CONCLUSION: The combined quantitative/qualitative protocol is an important advancement in evaluating individuals with DS and should be integrated into a more comprehensive evaluation of dynamic gait and lower limb analysis. PMID- 20353362 TI - Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models. AB - Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo. PMID- 20353363 TI - HIV drug resistance over the long haul. PMID- 20353364 TI - Treatment of active tuberculosis in HIV-coinfected patients: a systematic review and meta-analysis. AB - BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse. METHODS: A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta regression was performed using negative binomial regression. RESULTS: After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase (n=3352 patients from 35 study arms), thrice-weekly therapy (n=211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with > or =8 months, or if antiretroviral therapy was not used. CONCLUSIONS: This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this. PMID- 20353365 TI - Likely transmission of norovirus on an airplane, October 2008. AB - BACKGROUND: On 8 October 2008, members of a tour group experienced diarrhea and vomiting throughout an airplane flight from Boston, Massachusetts, to Los Angeles, California, resulting in an emergency diversion 3 h after takeoff. An investigation was conducted to determine the cause of the outbreak, assess whether transmission occurred on the airplane, and describe risk factors for transmission. METHODS: Passengers and crew were contacted to obtain information about demographics, symptoms, locations on the airplane, and possible risk factors for transmission. Case patients were defined as passengers with vomiting or diarrhea (> or =3 loose stools in 24 h) and were asked to submit stool samples for norovirus testing by real-time reverse-transcription polymerase chain reaction. RESULTS: Thirty-six (88%) of 41 tour group members were interviewed, and 15 (41%) met the case definition (peak date of illness onset, 8 October 2008). Of 106 passengers who were not tour group members, 85 (80%) were interviewed, and 7 (8%) met the case definition after the flight (peak date of illness onset, 10 October 2008). Multivariate logistic regression analysis showed that sitting in an aisle seat (adjusted relative risk, 11.0; 95% confidence interval, 1.4-84.9) and sitting near any tour group member (adjusted relative risk, 7.5; 95% confidence interval, 1.7-33.6) were associated with the development of illness. Norovirus genotype II was detected by reverse transcription polymerase chain reaction in stool samples from case patients in both groups. CONCLUSIONS: Despite the short duration, transmission of norovirus likely occurred during the flight. PMID- 20353367 TI - Cystatin C-based formula is superior to MDRD, Cockcroft-Gault and Nankivell formulae in estimating the glomerular filtration rate in renal allografts. AB - OBJECTIVES: There are conflicting reports on the reliability of the various glomerular filtration rate formula in renal allografts, to assess the performance of various glomerular filtration rate formula in estimating renal function of renal allografts. MATERIALS AND METHODS: Glomerular filtration rate was measured using an isotope Tc99m DTPA in 97 renal transplant patients and estimated using modification of diet in renal disease, Cockroft-Gault formula, Nankivell, and a cystatin C-based formula. The overall performance of these formula was evaluated by calculating bias, accuracy and precision. RESULTS: Mean age was 39.8 years ( /+ 12.7), body mass index was 26.9 (-/+ 6.3) and serum creatinine was 114.5 micromol/L (-/+ 39.3). The mean measured glomerular filtration rate was 58.1 mL/min (-/+ 25.6). The bias with modification of diet in renal disease was 7.7 (P = .03), with Cockroft-Gault formula it was 3.2 (P = .3), with Nankivell it was 10.3 (P = .0002), and with cystatin C it was 0.31 (P = .9) The precisions (r) for modification of diet in renal disease, Cockroft-Gault formula, Nankivell, and cystatin C were 0.26 (P = .01), 0.26 (P = .01), 0.42 (P = .0001), and 0.60 (P < .0001), respectively. We also investigated the impact of sex, age, body mass index, and glomerular filtration rate on the performance of these 4 formula. CONCLUSION: The best correlation, highest precision, accuracy, and least bias were seen when using cystatin C. The largest bias was seen when using Nankivell and modification of diet in renal disease formula. PMID- 20353368 TI - An international survey of the diagnosis, management, and treatment of hepatitis C in patients with end-stage renal disease. AB - OBJECTIVES: Hepatitis C is one of the leading causes of death from liver disease in the United States, and is frequently associated with renal disease. Two major organizations-the American Association for the Study of Liver Disease and the National Kidney Foundation-have published recommendations regarding the treatment of hepatitis C in the presence of chronic kidney disease; however, these guidelines do not always provide the same recommendations. Given the paucity of data on adherence to the current guidelines, a survey was conducted to provide information about the current practices of physicians in comparison to the published guidelines. MATERIALS AND METHODS: An observational study was conducted via a global survey asking physicians treating patients who had concurrent hepatitis C and chronic kidney disease. RESULTS: The 218 questionnaires collected requested the physician's subspecialty, the number of transplants performed at the hospital, the usual method of screening for hepatitis C, the preferred route, the indication and frequency of liver biopsy, the use of ribavirin and interferon, the use of hepatitis-C-positive donors in kidney transplant, and consent requirements. CONCLUSIONS: Our results showed that many physicians do not follow current recommendations. We argue that a consensus group be formed to set forth guidelines for the management of hepatitis C to optimize outcomes, and improve overall morbidity. PMID- 20353369 TI - Effect of pretransplant hemoglobin blood level on kidney transplant outcome. AB - OBJECTIVES: We investigated the effect of pretransplant hemoglobin level on the outcome of kidney transplant. PATIENTS AND METHODS: Patients were divided in 2 groups: group A < 10 g/dL (80 patients; PTHb < 10 g/dL), and group B > 10 g/dL (69 patients; PTHb = 10 g/dL), and were matched regarding donor age, recipient sex, blood group, donor recipient HLA, and Cytomegalovirus status. RESULTS: The frequency of acute rejection, together with the timing of rejection, the need for antithymocyte globulin Fresenius rescue therapy, infection rate, and posttransplant surgical complications were comparable between both groups. While the 1-year actuarial patient and graft survival rates, delayed graft function, and slow graft function rates were comparable between both groups, longer hospital stay was required for group B (> 10 g/dL) patients (P = .005). Mean serum creatinine levels upon discharge (P = .02), at 6 months (P = .05), and 1 year (P = .02) after discharge were higher in group B (> 10 g/dL) patients. While posttransplant hemoglobin levels were lower than pretransplant levels, they were higher in group B (> 10 g/dL) compared with group A (< 10 g/dL), (P = .019). CONCLUSIONS: Pretransplant hemoglobin level does not affect the outcome of kidney transplant, except for creatinine levels at 1 year. PMID- 20353366 TI - Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy. AB - BACKGROUND: Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. METHODS: We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. RESULTS: Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, > or =1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, > or =1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and > or =1 major PI IAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a PI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P=.98). CONCLUSIONS: In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen. PMID- 20353370 TI - Leflunomide derivative FK778 inhibits production of antibodies in an experimental model of alloreactive T-B cell interaction. AB - OBJECTIVES: The contribution of humoral immune response in allograft and xenograft rejection has been clearly demonstrated in recent years. For this reason, inhibition of alloantibody production has become essential in managing transplanted patients. Here, we assessed the effects of the leflunomide derivative FK778 (FK778) in the control of antibody production resulting from semiallogeneic cognate T-B-cell interactions. MATERIALS AND METHODS: BALB/c mice were tolerized at birth with semiallogeneic spleen cells from (BALB/c X C57BL/6) F1 mice, with or without overexpression of human bcl-2 transgene in B cells. These tolerized mice were treated with different dosages of FK778, either from birth, or from the third week of age, when autoantibody production was detected. The production of autoantibodies, used as markers of semiallogeneic cognate T-B - cell interactions, was evaluated at different time points during drug administration or after the interruption of treatment. RESULTS: FK778 treatment started at birth inhibited the production of semiallogeneic-driven antibodies in a dose-dependent manner. In addition, FK778 also reduced the levels of preformed circulating autoantibodies in adult mice, although the dosage required was 4 times higher than that used in neonates. However, the levels of IgG antibodies in these tolerized mice increased after FK778 withdrawal, indicating that FK778 failed to induce tolerance to semiallogeneic host CD4+ Th2 and/or donor B cells. CONCLUSIONS: Our results demonstrate the efficacy of FK778 in the control of antibody production resulting from semiallogeneic cognate T-B - cell interactions. PMID- 20353371 TI - The internet as a tool for patient-centered care in transplantation. AB - The Internet is a popular communication tool that plays a significant role in patient-centered care. It is argued that a driving force for the demand for online health information is the paucity of information easily obtained from traditional channels. As the quality of medical information available on the Internet is variable, and the quantity is constantly increasing and changing, there is a need for rigorous assessment of quality and effectiveness of health Web sites, and the Internet-based health care support services for different fields of medicine. On one hand, Internet-based patient support tools and Web sites have been used successfully in managing patients with different illnesses like lung transplant, vascular surgery, and treating diabetes mellitus - but on the other hand, other studies have shown that a majority of Web sites providing information on kidney and liver transplant are of poor quality and need overhauling. In the modern world, where e-technology has become common place, patients deserve e-services that are informative, trustworthy, and useful. It is not only a challenge, but also the responsibility of clinicians to make this happen. PMID- 20353372 TI - Characteristics of patients with Banff borderline changes in renal allograft biopsies. AB - OBJECTIVES: The aim of this retrospective study was to characterize the patients who experienced borderline rejection. MATERIALS AND METHODS: Patients with a minimum follow-up of 2 years were enrolled in this study. Forty-seven patients out of 106 patients with borderline rejection (after exclusion of those with associated chronic interstitial fibrosis) were compared with patients with acute cellular rejection grade 1 (n = 650), and patients free of rejection episodes (n = 444) regarding the different characteristics. RESULTS: Patients aged 20 years or younger were frequently in borderline rejection group than other groups (which was statistically significant) (P = .001). Significant differences were found in recipient and donor ages, consanguinity, pretransplant blood transfusion, and immunosuppression plan. Most patients in borderline rejection group received triple immunosuppression therapy than other groups (P = .001). Univariate and multivariate regression analysis of different variables on graft survival in borderline rejection patients revealed that none of them was statistically significant. CONCLUSIONS: Borderline rejection is a frequent finding in biopsy proven acute rejection after kidney transplant. Time of occurrence, frequency, treatment or not, and response to therapy were not predictors to graft survival. PMID- 20353373 TI - Impact of the addition of maintenance steroids to a rapid steroid discontinuation immunosuppressive protocol following acute renal transplant rejection. AB - OBJECTIVES: Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. MATERIALS AND METHODS: The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejection RESULTS: Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). CONCLUSIONS: More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection. PMID- 20353374 TI - Posttransplant soluble CD30 as a predictor of acute renal allograft rejection. AB - BACKGROUND: Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. MATERIALS AND METHODS: In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. RESULTS: Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 /+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). CONCLUSIONS: Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period. PMID- 20353375 TI - Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: A phase I/II clinical safety and primary efficacy data. AB - OBJECTIVE: We sought to assess the safety and therapeutic efficacy of autologous human bone marrow derived mononuclear cell transplantation on spinal cord injury in a phase I/II, nonrandomized, open-label study, conducted on 297 patients. MATERIALS AND METHODS: We transplanted unmanipulated bone marrow mononuclear cells through a lumbar puncture, and assessed the outcome using standard neurologic investigations and American Spinal Injury Association (ASIA) protocol, and with respect to safety, therapeutic time window, CD34-/+ cell count, and influence on sex and age. RESULTS: No serious complications or adverse events were reported, except for minor reversible complaints. Sensory and motor improvements occurred in 32.6% of patients, and the time elapsed between the injury and the treatment considerably influenced the outcome of the therapy. The CD34-/+ cell count determined the state of improvement, or no improvement, but not the degree of improvement. No correlation was found between level of injury and improvement, and age and sex had no role in the outcome of the cellular therapy. CONCLUSION: Transplant of autologous human bone marrow derived mononuclear cells through a lumbar puncture is safe, and one-third of spinal cord injury patients show perceptible improvements in the neurologic status. The time elapsed between injury and therapy and the number of CD34-/+ cells injected influenced the outcome of the therapy. PMID- 20353376 TI - Bentall procedure for the treatment of aortic dissection after cardiac transplant: a case report. AB - Aortic dissection affecting the donor aorta after cardiac transplant is a rarely seen complication. Data on the literature about the subject is restricted to case reports. Here, we present a case of type A aortic dissection after cardiac transplant that was successfully treated by the Bentall procedure. PMID- 20353377 TI - Peroneal neuropathy following liver transplantation: possible predisposing factors and outcome. AB - INTRODUCTION: Perioperative peroneal neuropathy is an uncommon complication following operations remote from the leg or in supine position including liver transplant. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 132 living-donor liver transplant recipients done at our center between September 2006 and December 2008. Various potential preoperative, intraoperative, and postoperative factors were studied in the cases that developed perioperative peroneal neuropathy. RESULTS: Peroneal neuropathy was reported in 7 recipients (5.3%) following liver transplant. Apart from intraoperative positioning, other identifiable predisposing factors appear to be poor nutritional status, tall and slender body shape, alcoholic liver disease, and higher pretransplant model for endstage liver disease score. All patients were treated conservatively, including nutritionally balanced diet and vitamin supplements combined with physical rehabilitation therapy. The motor power returned to normal within 6 months in all 7 patients. CONCLUSIONS: Perioperative peroneal neuropathy may be contributed by various preoperative factors apart from intraoperative nerve compression. It can be effectively prevented by being aware of the predisposing factors and implicating adequate precautions perioperatively. PMID- 20353378 TI - Hepatic abscesses after liver transplant: 1997-2008. AB - OBJECTIVES: Infectious complications (such as liver abscesses) remain one of the major causes of posttransplant morbidity and mortality. Management may be problematic and is often based on experience with hepatic abscess in nontransplant patients. We reviewed our experience with hepatic abscess in liver transplant recipients to assess their presentation, clinical features, treatment, and outcome. MATERIALS AND METHODS: A retrospective review of all liver transplant in Shiraz transplant center from September 1997 through September 2008 was performed. Hepatic abscess was defined as a parenchymal hepatic lesion consistent with abscess (as described by a radiologist), positive liver or concurrent blood cultures, or both (within 24 hours), and compatible clinical findings. RESULTS: Of 560 liver recipients, we identified 5 patients (23-42 y) who had experienced 7 episodes of hepatic abscess, 30-240 days after transplant. All patients had received liver from deceased donors. Biliary reconstruction was done by duct-to-duct anastomosis in 4 and hepatico-jejunostomy in 1 case. Pretransplant diagnoses included hepatitis B cirrhosis, autoimmune hepatitis (2 cases), Caroli disease, and cryptogenic cirrhosis. Liver aspirates showed E. coli in 4 cases, and Aspergillus in 1 case. The main predisposing factor was bile-to duct anastomosis stricture in 3, diabetes mellitus in 2, and hepatic artery thrombosis in 1 of the patients. Two patients died owing to liver and multiorgan failure, despite percutaneous and operative drainage with broad spectrum antibiotics and antifungals. CONCLUSIONS: Hepatic abscess, a rare complication after liver transplant, was associated with hepatic artery thrombosis, biliary anastomosis stricture, and diabetes mellitus. Mortality was higher than in patients who had not undergone transplant. Prolonged antibiotic therapy and drainage are required to improve the outcome in these patients. PMID- 20353379 TI - Off-pump coronary surgery for allograft vasculopathy 8 years after heart transplant. AB - Cardiac allograft vasculopathy is a severe complication after heart transplant, and is the major cause of death in patients surviving 1 year after transplant. We present a 59-year-old patient undergoing off-pump, coronary artery bypass surgery, 8 years after heart transplant. Owing to toxic liver disease, the lipid lowering therapy with statins had to be stopped 6 years after transplant, and coronary artery disease developed rapidly within 2 years. Off-pump, coronary bypass surgery was performed using a new, multisuction cardiac positioner; a disposable stabilizer; and a proximal seal system to avoid clamping of the aorta. The patient received 3 bypass grafts: the left internal thoracic artery; to the left anterior descending coronary artery; 1 saphenous vein graft to the marginal branch of the circumflex artery; and 1 saphenous vein graft to the right coronary artery. His postoperative course was uneventful. PMID- 20353380 TI - Epididymo-orchitis and central nervous system nocardiosis in a bone marrow transplant recipient for acute lymphoblastic leukemia. AB - OBJECTIVES: We report a case of epididymo-orchitis and central nervous system nocardiosis in a 22-year-old man with T-cell acute lymphoblastic leukemia; he was an allogeneic marrow recipient with acute and chronic graft-versus-host disease. MATERIALS AND METHODS: He had microscopic hematuria and cytomegalovirus antigenemia. He deteriorated subsequently while on cyclosporine and steroids, requiring hospital admission owing to fever and swelling of the left testis and generalized tonic-clonic convulsions. RESULTS: Brain magnetic resonance imaging showed abnormal signal area in right parietal and left parieto-occipital lobes. The lesions had mass effect, edema, and ring enhancement. Findings were indicative of a brain abscess. A testicular biopsy from the lower pole of the left testis was done. A white-to-yellowish discharge was seen and subsequently, Nocardia grew in culture. CONCLUSIONS: Trimethoprim-sulfamethoxazole was prescribed, and significant improvement was seen after 2 weeks. The patient was discharged. He was subsequently referred after 3 weeks due to graft-versus-host disease and died of pancytopenia. PMID- 20353381 TI - Targeting resveratrol to mitochondria for cardiovascular diseases. AB - Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Considering the central role of mitochondria in cell signaling, growth and death, in the present paper we have tried to summarize the present data including patents and discuss the beneficial effects of resveratrol on cardiovascular diseases from the mitochondria perspective. PMID- 20353382 TI - Ethnobotanical bioprospection of candidates for potential antimicrobial drugs from Brazilian plants: state of art and perspectives. AB - Despite of the high biological diversity and traditional use of medicinal plants in Brazil, no comprehensive ethnobotanic review of plants with potential antimicrobial effects is available. In the present work own field information is aggregated with a literature review, identifying 433 Brazilian plant species potentially useful for identification of antimicrobial peptides. They included mainly woody species, distributed on 100 plant families (93 angiosperms and 7 pteridophytes) and 266 genera, covering all Brazilian regions and ecosystems. Main plant parts and indications for their use are presented and discussed, revealing the high potential that these plants present for the future planning strategies regarding the future development of antimicrobial drugs. PMID- 20353384 TI - New drug delivery systems in inflammatory bowel disease: MMX and tailored delivery to the gut. AB - Inflammatory bowel diseases are chronic diseases that affect the gastrointestinal tract. Mesalamine, corticosteroids, immunosuppressants and biological agents are currently used to treat these diseases. Due to inadequacies of the currently available delivery systems, a large number of patients do not respond to treatment, especially when they are affected by distal colonic disease. Multimatrix (MMX) technology comprises hydrophilic and lipophilic excipients, enclosed within a gastro-resistant, pH-dependent coating. This new delivery technology has been used to modify some commonly used drugs, including mesalamine and budesonide, as well as heparin, which are now being investigated for their utility in the management of IBD. AIM: The aim of this review is to explore the MMX delivery technology and its efficacy for the treatment of IBD. RESULTS: The results of various studies involving MMX drugs have been published. Mesalamine MMX induces clinical and endoscopic remission in patients with mild to moderate ulcerative colitis (UC) compared with placebo. Positive results have also been observed with MMX budesonide in two phase I studies. In a pilot study involving ten patients with UC, efficacy of heparin-MMX as an IBD therapy was observed. CONCLUSION: MMX is a promising new delivery system that can improve efficacy of current and new drugs, augmenting targeting to the affected tract, thereby increasing response and remission rates for those drugs in patients with IBD. PMID- 20353383 TI - Ginsenoside Rbeta1 reduces neurologic damage, is anti-apoptotic, and down regulates p53 and BAX in subarachnoid hemorrhage. AB - Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent. PMID- 20353385 TI - Gene therapy for acute liver failure. AB - Acute liver failure (ALF) is a life-threatening medical emergency and occurs when the liver rapidly loses its function within a short period. ALF can develop secondary to a variety of causes. Currently, the orthotopic liver transplantation is the "Gold Standard" therapy for the disease. However, due to the limited availability of donor organs and rapid progression of the disease, the mortality of ALF remains high. Therefore, it is imperative to develop novel therapeutic reagents for ALF. Gene therapy by delivering a target gene to the patients appears to be a promising approach for the treatment of ALF. Here, we review the recent advance of gene therapy for ALF, focusing on the three technical elements, animal models, vehicles for gene delivery and technique for gene delivery, which are important for the success of gene therapy as well as the potential targets used for the treatment of ALF. PMID- 20353386 TI - siRNA delivery using nanocarriers - an efficient tool for gene silencing. AB - Small interfering RNAs (siRNA) are one of the most recent additions used to silence gene expression. At present siRNA is the most extensively used gene silencing technique over other nucleic-acid based approaches to treat disease including cancer, hepatitis, respiratory disease, cardiovascular diseases, neuronal disease and autoimmune disease. However, systemic delivery of siRNA in vivo, remains to be the biggest challenge to be overcome. Various strategies have been developed to deliver siRNA efficiently into target cell such as chemical modification of siRNA, physical strategies, viral and non viral-vectors mediated delivery. Among all the approaches non viral vectors including lipoplexes and polyplexes were found to be most successful which have been reviewed in this article. Further therapeutic applications of RNAi have also been briefly reviewed. PMID- 20353387 TI - Susceptibility of HIV-1 to tipranavir and other antiretroviral agents in treatment-experienced patients: The UTILIZE Study. AB - OBJECTIVES: The primary objective was to assess HIV-1 susceptibility to the protease inhibitor (PI) tipranavir and other antiretroviral (ARV) agents among treatment-experienced patients (TEP). Secondarily, clinicians' use of resistance testing was examined. METHODS: UTILIZE was an observational study conducted at 40 sites in the United States. Patients currently failing a PI-based regimen were randomized to receive either a genotype (GT) or combined phenotype-genotype test (PGT) and a treatment decision was made at the second study visit. RESULTS: 246 patients enrolled, 236 had resistance test results, and 139 (59%) had evidence of HIV-1 resistance to >or=1 PI. Among these 139 patients, more than 50% had viruses that remained sensitive to tipranavir and darunavir, whereas susceptibility to other PIs was markedly lower (<22%). Increasing prior PI exposure was associated with reduced susceptibility to most ARV agents. After obtaining resistance test results, 83% of patients changed therapy. Newly available or investigational ARVs were used frequently. The reason investigators most often cited for changing therapy was the patient resistance test results (82%) and the most common reason for not changing therapy was the inability to construct an active regimen. The majority of patients who exhibited PI resistance received two or more active agents in the new regimen. CONCLUSIONS: Overall, 59% of TEPs failing a PI-based regimen had HIV-1 with PI resistance. The majority of these patients' viruses remained sensitive to either tipranavir or darunavir. Investigators used results from resistance assays to construct a new regimen, frequently with newer agents. In PI-experienced patients, tipranavir and darunavir remain the most likely available active PIs. PMID- 20353388 TI - Quality of life of HIV patients in a rural area of western Uganda: impact of a community-based antiretroviral treatment program. AB - OBJECTIVE: Community-based antiretroviral treatment (CBART) programs should aim to achieve positive quality of life outcomes. The purpose of this study was to investigate changes in the health related quality of life (HRQOL) outcomes of patients in a CBART program supported by community volunteers in one sub-county in western Uganda located 50 km from the nearest urban centre. METHODS: We administered a translated version of the MOS-HIV survey and collected clinical data at baseline and after one year from 130 patients. Inclusion criteria included residency in the sub-county, eighteen years of age or, treatment-naive, eligible for ART based on CD4 cell count <200 cells/mm3 or WHO clinical stage 3 or 4, and willing to accept daily treatment support by family/friends and to be visited by a community volunteer weekly. We assessed changes in physical health (PHS) and mental health (MHS) summary scores and examined associations between patient characteristics and changes in HRQOL. RESULTS: After one year, we observed significant increases in mean PHS (42.7 to 50.1; p<0.01) and MHS (43.5 to 49.5; p<0.01) scores. Lower age (p<0.01) and lower baseline PHS scores (p<0.01) were associated with increases in PHS scores and lower age (p=0.03) and lower baseline MHS scores (p<0.01) were associated with increases in MHS scores. Fifteen patients (12%) had reductions in their HRQOL after one year which were not associated with patient or clinical characteristics, including virological suppression. CONCLUSIONS: The observed improvements in HRQOL demonstrate that positive treatment outcomes can be achieved in CBART programs in rural Uganda. However, some patients appear to experience declines in their overall well-being, despite achieving virological suppression. HRQOL surveys can be useful in identifying these patients, who may require additional attention and support to achieve the full benefits of ART. PMID- 20353389 TI - The association of lipodystrophy and oxidative stress biomarkers in HIV-infected men. AB - The aim of this study was to describe the status of oxidative stress and antioxidant biomarkers and their association with metabolic and body composition components of HIV-lipodystrophy syndrome. In a cross-sectional study of blood samples from HIV-infected men with lipodystrophy syndrome (HIV+LIPO+ = 10), HIV infected men without lipodystrophy syndrome (HIV+LIPO- = 22), and healthy subjects (control = 12), the following oxidative stress biomarkers were analyzed: total hydroperoxide, thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP). In addition, antioxidant biomarkers, including total glutathione, uric acid, alpha-tocopherol, and metabolic components were tested. Dual-energy x-ray absorciometry (DXA) was used to measure the fat mass. The duration of HIV infection and the duration and type of highly active antiretroviral therapy were similar between the two HIV-infected groups. Higher levels of total hydroperoxide were observed in the HIV+LIPO+ (50 +/- 33 H(2)O(2)/L) group compared to the HIV+LIPO- (19 +/- 13 H(2)O(2)/L) and control (5 +/- 5 H(2)O(2)/L) groups (p < 0.05). Similarly, higher levels of AOPP were observed in the HIV+LIPO+ (326 +/- 173 micromol/L) group compared to the HIV+LIPO (105 +/- 92 micromol/L) and control groups (80 +/- 20 micromol/L) (p < 0.05). Total hydroperoxide significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.47, p < 0.05) and HIV+LIPO- groups (r = 0.29, p < 0.05), while AOPP significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.73, p < 0.05) and HIV+LIPO- (r = 0.54, p < 0.05) groups. Therefore, higher lipid and protein oxidation were found in HIV-infected patients with lipodystrophy syndrome, and both were associated with insulin levels. PMID- 20353390 TI - Involvement of regulatory T cells in HIV immunopathogenesis. AB - Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex biology of these cells, including maintenance of immunological tolerance to "self" and regulation of immune responses to pathogens, commensals, and tumors, has become the focus of intense investigation. The ability to control the infection and to delay the progression of the infection to AIDS and/or death is probably regulated by a balance between host factors, such as immunologic response and viral factors. Different rates of disease progression among HIV-1 infected individuals have been observed. In this context, Tregs may play an important role in the immunopathology of HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. In this review, we present the molecular and immunological aspects of Tregs in the HIV system and the association between Tregs and highly active antiretroviral therapy (HAART). PMID- 20353391 TI - HIV-induced abnormalities in myelopoiesis and their recovery following antiretroviral therapy. AB - HIV-1 infection is associated with hematologic abnormalities including defective myelopoiesis. Most studies of myelopoiesis during HIV-1 infection were performed using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter-individual variability in the numbers of cultured precursors. Here we evaluated the myelopoietic potential of circulating CD34+ progenitors by conducting a longitudinal analysis of antiretroviral therapy (ART)-induced changes of colony forming units-granulocyte and monocyte (CFU-GM) growth. Twelve HIV-infected individuals were studied longitudinally before and after initiation of ART (i.e. at a time when plasma HIV-RNA levels had become undetectable); thirty-one HIV-uninfected healthy individuals were enrolled as controls. Peripheral blood-derived CD34+ progenitors were purified by immunomagnetic sorting, and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor and interleukin-3. ART induced changes in the proportion of CD8+ T cells expressing surface HLA-DR were also evaluated. We found that CFU-GM levels were increased in untreated HIV infected individuals when compared to uninfected controls but declined significantly following ART, in parallel with the decline of HIV-RNA levels in plasma and with the down-regulation of HLA-DR expression on CD8+ T cells. These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective myelopoiesis and accumulation of myeloid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of CFU-GM levels. PMID- 20353392 TI - A decrease in the cellular phosphodiester to phosphomonoester lipid ratio is characteristic of HIV-1 infection. AB - The ability to detect HIV-1 in tissues that are not readily amenable to biopsy greatly limits the diagnosis and control of HIV infection, and ultimately, our ability to understand HIV-induced disease pathology. In view of this, we explored the utility of diagnostically measuring HIV-1 infection using (31)P nuclear magnetic resonance ((31)P-NMR). (31)P-NMR enables the correlation of infection to changes in the concentration of specific intracellular metabolites, macromolecules and of bioenergetic parameters that are key to mammalian cell physiology. Examples include primary components of biological membranes such as phosphomonoester (PME) and phosphodiester (PDE) lipids. Using (31)P-NMR we found that changes in the ratio of PDE/PME in human cell lines and primary isolates were significantly altered following HIV-1 infection. Our findings showed that the ratio of cellular PDE/PME uniformly decreased 2.00-2.26 fold in HIV-1 infected cells. Using the altered PDE/PME ratio as a selection criterion, we next assessed HIV-1 infection in lymphocytes isolated from both HIV-1 seropositive and non-infected human subjects. A decreased PDE/PME ratio was characteristic of HIV 1 infection in each instance. These results demonstrate that changes in cellular phospholipids induced during HIV-1 infection may be used to uncover basic mechanisms of HIV-1 pathology, and potentially, may be extrapolated to explore the application of NMR analysis as a technique for imaging infected organs and tissues in situ. PMID- 20353393 TI - Role of dendritic cells in HIV-immunotherapy. AB - HIV remains one of the most important deadly infections today, due to the lack of a preventive vaccine and limited access to medical care in developing countries. In developed countries, antiretroviral therapy is available, but it can not eliminate the virus, implying that life-long therapy is necessary. Therefore, it is important that other strategies such as therapeutic vaccination will be developed to control virus replication or even eliminate the virus. The major obstacles towards such a strategy are the huge variability of the virus and the profound HIV-induced immune dysfunction. In this review we focus on dendritic cell based immunotherapies against HIV. To develop an efficient immunotherapy, several elements should be taken into account such as which antigen and loading strategy to use, how to deliver the immunogen, how to optimize the interaction between antigenic peptide and T cells and avoid tolerance. Clearly, to develop an immunotherapy to complement the effect of HAART, it is not sufficient to enhance T cell responses against a consensus sequence or against the prevailing plasma virus. Broad and potent immune response are needed to suppress the entire quasispecies, including the latent reservoir, and to prevent any escape. PMID- 20353394 TI - Induction of protective immunity against microbial challenge by targeting antigens expressed by probiotic bacteria to mucosal dendritic cells. AB - Efficient vaccines combined with adjuvants potentiate and enhance antibody avidity and increase T cell longevity, particularly in individuals with compromised immunity. The efficacy of a novel vaccine can be improved by specifically targeting its immunogenic subunits and expressing it in live probiotic vector (i.e. Lactobacillus acidophilus) that protects vaccine bioavailability and to induces not only mucosal but also systemic immunity against microbes. Accordingly, our data clearly show that specific Lactobacillus species (L. gasseri) not only optimally activate DCs but also deliver targeted antigens to mucosal DCs via 12-mer peptides derived from a phage display library resulting in robust humoral and T cell immunity against microbial challenge. This effort is accomplished via novel tools that provide "targeting" of the vaccine, evaluation of innovative vaccine effectiveness against a wide array of microbes, and controlling gene expression/presentation technologies in probiotic lactobacilli that can be orally consumed at high levels resulting in natural delivery of a "targeted" antigen to mucosal DCs. In this review I will discuss the potential benefits and efficacy of the employed vaccine strategy that may be feasible for various studies in the field. PMID- 20353395 TI - Mucosal adjuvants. AB - The vast majority of pathogens invade the body through or establish infections in the mucosal tissues. Development of vaccines to combat mucosal infections represents a top priority. Mucosal immunization has recently attracted much interest as a means of generating protective immunity against mucosal pathogens. Conversely, only very few mucosal vaccines are presently approved for human use. The development of a broad range of mucosal vaccines will necessitate the development of safe and effective mucosal adjuvants and delivery systems. Over the past decade, a number of immunomodulatory agents, including toxin based adjuvants, Toll like receptor (TLR) mimetics and non TLR-targeting immunostimulators as well as delivery systems have shown promise for mucosal administration in experimental animals. However, their possible use in humans remains to be established. This paper attempts to provide a brief overview of the mucosal immunization and adjuvants with an emphasis on mucosal adjuvants in or close to clinic. PMID- 20353396 TI - Toward integrase defective lentiviral vectors for genetic immunization. AB - Genetic immunization with lentiviral vectors is under evaluation as a means for induction of sustained immune response. Lentiviral vectors showed reduced antivector immune responses and efficiently transduce post-mitotic cells in vivo, including antigen presenting cells, such as dendritic cells and macrophages, thus providing a significant benefit over other vector-based antigen delivery platforms. Several evidences indicate that a single immunization with lentiviral vectors induces strong and sustained effector and memory T-cell immune responses, as well as antibody production. New generation of lentiviral vectors with improved biosafety profile are also under development. In particular, integration defective lentiviral vectors have been generated and used as an efficient and safe delivery system for both gene therapy and immunization purposes. Taken together, these evidences support the ongoing development of lentiviral vector based genetic immunization strategies for safe applications in the clinic. PMID- 20353398 TI - Virus-like particles as particulate vaccines. AB - Particulate structures hold great promise for the development of effective and affordable recombinant prophylactic as well as therapeutic vaccines. Different types of particulate structures, including virus-like particles (VLPs) and virosomes, have been developed depending on the nature of the viral pathogen to be targeted and the type of immune response (humoral vs cellular) to be elicited. Particulate structures allow the insertion or fusion of foreign antigenic sequences, resulting in chimeric particles delivering foreign antigens on their surface. Similarly, they are used as carriers for foreign antigens, including non protein antigens, via chemical conjugation. Particulate structures, indeed, represent a very efficient system for delivering antigens to antigen presenting cells (APC) which, in turn, trigger and amplify the adaptive immune response. The present review will address the biological and immunological properties of particulate structures, in particular VLPs, as platform for vaccine development. PMID- 20353399 TI - Orexins and gastrointestinal functions. AB - Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointestinal functions: animal studies have indeed demonstrated that centrally-injected orexins or endogenously released orexins in the brain stimulates gastric secretion and influence gastrointestinal motility. The subsequent identification of orexins and their receptors in the enteric nervous system (including the myenteric and the submucosal plexuses) as well as in mucosa and smooth muscles has suggested that these neuropeptides may also play a local action. In this view, emerging studies indicate that orexins also exert region specific contractile or relaxant effects on isolated gut preparations. The aim of the proposed review is to summarize both centrally- and peripherally-mediated actions of orexins on gastrointestinal functions and to discuss the related physiological role on the basis of the most recent findings. PMID- 20353400 TI - Structural basis for the efficient phosphorylation of AZT-MP (3'-azido-3' deoxythymidine monophosphate) and dGMP by Plasmodium falciparum type I thymidylate kinase. AB - Plasmodium falciparum is the causative agent of malaria, a disease where new drug targets are required due to increasing resistance to current anti-malarials. TMPK (thymidylate kinase) is a good candidate as it is essential for the synthesis of dTTP, a critical precursor of DNA and has been much studied due to its role in prodrug activation and as a drug target. Type I TMPKs, such as the human enzyme, phosphorylate the substrate AZT (3'-azido-3'-deoxythymidine)-MP (monophosphate) inefficiently compared with type II TMPKs (e.g. Escherichia coli TMPK). In the present paper we report that eukaryotic PfTMPK (P. falciparum TMPK) presents sequence features of a type I enzyme yet the kinetic parameters for AZT-MP phosphorylation are similar to those of the highly efficient E. coli enzyme. Structural information shows that this is explained by a different juxtaposition of the P-loop and the azide of AZT-MP. Subsequent formation of the transition state requires no further movement of the PfTMPK P-loop, with no steric conflicts for the azide moiety, allowing efficient phosphate transfer. Likewise, we present results that confirm the ability of the enzyme to uniquely accept dGMP as a substrate and shed light on the basis for its wider substrate specificity. Information resulting from two ternary complexes (dTMP-ADP and AZT-MP-ADP) and a binary complex with the transition state analogue AP5dT [P1-(5'-adenosyl)-P5-(5' thymidyl) pentaphosphate] all reveal significant differences with the human enzyme, notably in the lid region and in the P-loop which may be exploited in the rational design of Plasmodium-specific TMPK inhibitors with therapeutic potential. PMID- 20353402 TI - Discovering plant metabolic biomarkers for phenotype prediction using an untargeted approach. AB - Biomarkers are used to predict phenotypical properties before these features become apparent and, therefore, are valuable tools for both fundamental and applied research. Diagnostic biomarkers have been discovered in medicine many decades ago and are now commonly applied. While this is routine in the field of medicine, it is of surprise that in agriculture this approach has never been investigated. Up to now, the prediction of phenotypes in plants was based on growing plants and assaying the organs of interest in a time intensive process. For the first time, we demonstrate in this study the application of metabolomics to predict agronomic important phenotypes of a crop plant that was grown in different environments. Our procedure consists of established techniques to screen untargeted for a large amount of metabolites in parallel, in combination with machine learning methods. By using this combination of metabolomics and biomathematical tools metabolites were identified that can be used as biomarkers to improve the prediction of traits. The predictive metabolites can be selected and used subsequently to develop fast, targeted and low-cost diagnostic biomarker assays that can be implemented in breeding programs or quality assessment analysis. The identified metabolic biomarkers allow for the prediction of crop product quality. Furthermore, marker-assisted selection can benefit from the discovery of metabolic biomarkers when other molecular markers come to its limitation. The described marker selection method was developed for potato tubers, but is generally applicable to any crop and trait as it functions independently of genomic information. PMID- 20353397 TI - Recombinant Mycobacterium bovis BCG as an HIV vaccine vector. AB - HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID- 20353401 TI - Determination in oocytes of the reproductive modes for the brine shrimp Artemia parthenogenetica. AB - The brine shrimp, Artemia, reproduces either oviparously, producing encysted embryos (diapause cysts), or ovoviviparously, producing free-swimming nauplii. Environmental factors, such as photoperiod, have been applied to control the reproduction mode of Artemia, but when the determination of a reproductive mode occurs remains unknown. We analysed the differential gene expression between oocytes from oviparous and ovoviviparous Artemia reared under different photoperiods. A total of 692 qualified cDNA clones were obtained by subtractive hybridization, 327 of which matched GenBank(r) Nucleotide Sequence Database entries. Gene expressions of 44 cDNAs (representing 56 clones) were analysed in oocytes using real-time PCR. Among these genes, 11 (21 clones) were significantly (P<0.05) up-regulated and 7 (9 clones) down-regulated in Artemia oocytes that subsequently enter diapause. Remarkably, known diapause-related proteins such as ArHsp22 (Artemia heat-shock protein 22) and chitin-binding proteins are found to be already differentially expressed. Furthermore, RNAi (RNA interference) knockdown of a differentially expressed gene, polo-like kinase 1, in oocyte of ovoviviparous Artemia led to the production of white embryos rather than free swimming nauplii. In summary, our results provide evidence at the molecular level that the reproductive mode of Artemia is already determined at the oocyte stage of their life cycle. PMID- 20353403 TI - Nitrogen fixation persists under conditions of salt stress in transgenic Medicago truncatula plants expressing a cyanobacterial flavodoxin. AB - Several recent studies have demonstrated that the expression of a cyanobacterial flavodoxin in plants can provide tolerance to a wide range of environmental stresses. Indeed, this strategy has been proposed as a potentially powerful biotechnological tool to generate multiple-tolerant crops. To determine whether flavodoxin expression specifically increased tolerance to salt stress and whether it might also preserve legume nitrogen fixation under saline conditions, the flavodoxin gene was introduced into the model legume Medicago truncatula. Expression of flavodoxin did not confer saline tolerance to the whole plant, although the sensitive nitrogen-fixing activity was maintained under salt stress in flavodoxin-expressing plants. Our results indicate that flavodoxin induced small but significant changes in the enzymatic activities involved in the nodule redox balance that might be responsible for the positive effect on nitrogen fixation. Expression of flavodoxin can be regarded as a potential tool to improve legume symbiotic performance under salt stress, and possibly other environmental stresses. PMID- 20353404 TI - Transgenic plants as a source for the bioscavenging enzyme, human butyrylcholinesterase. AB - Organophosphorous pesticides and nerve agents inhibit the enzyme acetylcholinesterase at neuronal synapses and in neuromuscular junctions. The resulting accumulation of acetylcholine overwhelms regulatory mechanisms, potentially leading to seizures and death from respiratory collapse. While current therapies are only capable of reducing mortality, elevation of the serum levels of the related enzyme butyrylcholinesterase (BChE) by application of the purified protein as a bioscavenger of organophosphorous compounds is effective in preventing all symptoms associated with poisoning by these toxins. However, BChE therapy requires large quantities of enzyme that can easily overwhelm current sources. Here, we report genetic optimization, cloning and high-level expression of human BChE in plants. Plant-derived BChE is shown to be biochemically similar to human plasma-derived BChE in terms of catalytic activity and inhibitor binding. We further demonstrate the ability of the plant-derived bioscavenger to protect animals against an organophosphorous pesticide challenge. PMID- 20353405 TI - Cost-efficient screening for BK virus in pediatric kidney transplantation: a single-center experience and review of the literature. AB - BKVNP is an increasingly recognized cause of graft dysfunction and loss in kidney transplant recipients. Protocols for BKV screening and for the diagnosis of BKVNP are still evolving. PCR-based BKV detection became available at our institution in 2007, when we began using it according to published guidelines. We subsequently reviewed our experience with urine and plasma BKV PCR testing in our pediatric kidney transplant recipient population. We found rates of viruria, viremia, and BKVNP that were similar to the published literature. We also conducted a cost analysis suggesting that urine PCR testing, as used by us, is not cost efficient in the detection of BKV. We conclude that plasma only-based PCR testing for BKV may be sufficient in most clinical settings. PMID- 20353406 TI - Optimal approach to prevent veno-occlusive disease following hematopoietic stem cell transplantation in children. PMID- 20353407 TI - Cytokine kinetics profiling in pediatric renal transplant recipients. AB - Pediatric renal transplant recipients experience side effects of immunosuppression. Few immunoassays exist which can assess the adequacy of immunosuppression. We developed a CKT, whereby cytokine levels are measured in a five-day mixed lymphocyte reaction. We describe the in vitro cytokine responses to donor and third-party antigen in a pilot study of nine children after living donor renal transplantation. The CKT identified five patterns of IFN-gamma secretion relative to donor and third-party alloantigen: no response to alloantigen (n = 2), hypo-response to donor (n = 3), equal response (n = 1), hyper-response to donor (n = 1), and intermediate response (n = 2). IL-2 and IL 13 patterning correlated with IFN-gamma expression. Two of nine subjects had acute rejection, which correlated with intermediate and hyper-responsive profiles. No rejection occurred during immunosuppression or donor-specific hypo responsiveness. Significant immunosuppression was universal early after transplantation. Two of four children showed strong pretransplant responses to donor, which were regained three months post-transplant, and associated with rejection in one subject. The CKT reflects the level of immunosuppression and may offer a method to assess the adequacy of immunosuppression. A pattern of complete non-responsiveness or hypo-responsiveness correlated with lack of acute rejection. The CKT may prove useful in titrating immunosuppression and in improving live donor selection. PMID- 20353408 TI - The adverse effects of comorbid pain on depression outcomes in primary care patients: results from the ARTIST trial. AB - OBJECTIVES: To explore the effect of pain symptoms and improvements in pain on depression outcomes. METHODS: We analyzed data from A Randomized Trial Investigating SSRI Treatment (ARTIST), a randomized longitudinal effectiveness study comparing selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression in primary care (n = 573). Depression outcome at month 6, defined as remission, partial response, and nonresponse using the Symptom Checklist-20, was the primary outcome. RESULTS: Compared to patients with no pain at baseline, those with severe pain were less likely to achieve remission (OR = 0.11, 95% CI 0.05-0.25) and partial response (OR = 0.24, 95% CI 0.10-0.59) vs nonresponse. Patients with moderate pain were less likely to achieve remission vs nonresponse (OR = 0.25, 95% CI 0.13-0.48). Patients with early improvement in pain were more likely to achieve remission (OR = 1.90, 95% CI 1.03-3.49). Accounting for missing data with last observation carried forward or multiple imputation yielded similar results. CONCLUSION: Pain symptoms are present in the majority of depressed primary care patients beginning antidepressant therapy. Pain symptoms are associated with worse depression outcomes, while improvement in pain is associated with significantly better depression outcomes. Attention to comorbid pain may be important in enhancing depression care. PMID- 20353409 TI - The "swimmer's view" as alternative when lateral view is inadequate during interlaminar cervical epidural steroid injections. AB - OBJECTIVE: To present a technique that better visualizes the needle during interlaminar cervical epidural steroid injection (ICESI) in patients where the lateral view is inadequate. DESIGN: Case report. SETTING: Private group practice. SUBJECT: A 57-year-old morbidly obese male presenting for ICESI for left neck and upper limb pain after a motor vehicle accident. Magnetic resonance imaging revealed left C6-7 herniated nucleus pulposis and C4-5 osteophytic disc-ridge complex. Electrodiagnostic evaluation revealed activity consistent with a left C7 radiculopathy. INTERVENTION: Left C7-T1 ICESI. Needle was obscured in the lateral view by the patient's shoulders. Needle was made visible by positioning the patient for Swimmer's view. RESULTS: Full resolution of symptoms without associated complications. CONCLUSIONS: Grave complications have been associated with ICESI necessitating impeccable and systematic technique with substantial knowledge of anatomy. Although injection at lower levels is advocated for safety concerns, the needle during lateral view may be obscured by the shoulders in some patients. The "Swimmer's View" position may be attempted when lateral view is insufficient to visualize needle during ICESI. PMID- 20353410 TI - God image and happiness in chronic pain patients: the mediating role of disease interpretation. AB - OBJECTIVE: The present study explored the role of the emotional experience of God (i.e., positive and negative God images) in the happiness of chronic pain (CP) patients. Framed in the transactional model of stress, we tested a model in which God images would influence happiness partially through its influence on disease interpretation as a mediating mechanism. We expected God images to have both a direct and an indirect (through the interpretation of disease) effect on happiness. DESIGN: A cross-sectional questionnaire design was adopted in order to measure demographics, pain condition, God images, disease interpretation, and happiness. One hundred thirty-six CP patients, all members of a national patients' association, completed the questionnaires. RESULTS: Correlational analyses showed meaningful associations among God images, disease interpretation, and happiness. Path analyses from a structural equation modeling approach indicated that positive God images seemed to influence happiness, both directly and indirectly through the pathway of positive interpretation of the disease. Ancillary analyses showed that the negative influence of angry God images on happiness disappeared after controlling for pain severity. CONCLUSION: The results indicated that one's emotional experience of God has an influence on happiness in CP patients, both directly and indirectly through the pathway of positive disease interpretation. These findings can be framed within the transactional theory of stress and can stimulate further pain research investigating the possible effects of religion in the adaptation to CP. PMID- 20353411 TI - Gabapentin does not reduce preoperative anxiety when given prior to total hip arthroplasty. AB - INTRODUCTION: Gabapentin is an anti-epileptic drug which is also used for the treatment of postoperative pain and a variety of psychiatric diseases including chronic anxiety disorders. We tested the hypothesis that compared with a placebo control, gabapentin would reduce preoperative anxiety in patients undergoing total hip arthroplasty. METHODS: Following ethics approval, patients participating in a larger double blind, randomized, trial of multimodal analgesia were given either gabapentin 600 mg (N = 22) or placebo (N = 48) 2 hours before spinal anesthesia. Prior to administering the study medication, baseline anxiety levels were measured using a visual analog scale (VAS). Two hours after the ingestion of gabapentin or placebo, and prior to surgery, patients again rated their anxiety using a VAS. RESULTS: Anxiety scores did not differ significantly between the groups either before (P = 0.95) or 2 hours after (P = 0.61) ingestion of gabapentin or placebo. Baseline anxiety and postdrug anxiety scores failed to demonstrate a significant association with maximal postoperative pain at rest, maximal postoperative pain with movement, and cumulative morphine consumption 48 hours after surgery. CONCLUSIONS: Administration of gabapentin 600 mg prior to surgery does not reduce preoperative anxiety. PMID- 20353412 TI - An anatomic-based approach for the placement of implantable loop recorders. AB - INTRODUCTION: Placement of the Reveal implantable loop recorder (ILR; Medtronic Inc., Minneapolis, MN, USA) has previously involved preoperative cutaneous mapping to determine the optimal location. We describe an anatomic-based approach to ILR placement that does not require cutaneous mapping. METHOD: A total of 63 patients (40 women, 23 men, mean age 38 +/- 15 years) were included in the study. Each underwent implantation of a Reveal ILR in the left upper chest area midway between the supraclavicular notch and the left breast area. Thirty-two patients received a Medtronic Reveal DX ILR and 31 received Reveal XT device. RESULTS: In all 62 patients, adequate electrocardiographic tracings were obtained at implant without the need for preoperative cutaneous mapping, and all were followed for a period of 10 +/- 4 months afterwards. The mean P wave amplitude was 0.12 +/- 0.20 mV at implant and at follow-up (6-14 months postimplant); the amplitude was 0.11 +/- 0.19 mV. The peak-to-peak QRS amplitude was 0.48 +/- 0.15 mV at implant and 0.44 +/- 0.16 mV at a follow-up of 6-14 months. The P waves were not detected in two patients at follow-up. In one patient, decreased amplitude of QRS complex resulted in the autoactivation of the device and in one other patient noise was inappropriately oversensed and recorded. CONCLUSION: A simple anatomic approach can be used for reveal ILR placement. PMID- 20353413 TI - Utilization of defibrillators and resynchronization therapy at the time of evaluation at a heart failure and cardiac transplantation center. AB - BACKGROUND: Internal cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality, but are underutilized in routine clinical practice. The use of these devices in patients at the time of an initial evaluation at an advanced heart failure and cardiac transplantation center is unknown. METHODS: We retrospectively analyzed consecutive patients who were enrolled in a database examining parameters of cardiopulmonary exercise testing in chronic heart failure (CHF) patients at the time of an initial outpatient evaluation at a tertiary care center. Rates of ICD and CRT use in eligible patients were determined. RESULTS: Two hundred two patients had an average age of 54 +/- 13 years and an average peak oxygen consumption (pVO(2)) of 12.5 +/- 4.5 mL/kg/min. Of 97 patients eligible for an ICD only, 57% had an ICD at the time of evaluation. Sixty-four percent of ICD-eligible male patients had an ICD compared to 36% of ICD-eligible female patients (P = 0.015). Of 105 patients meeting criteria for CRT, 54% had a CRT device. There was no difference between CRT use in eligible male and female patients. CONCLUSIONS: ICDs and CRT are underutilized in patients with severe CHF at the time of evaluation at a tertiary care center despite young age, objective functional limitation, and active consideration for advanced CHF therapies. Female patients have lower rates of ICD use than male patients. PMID- 20353414 TI - Grouped beating during narrow complex tachycardia: what is the mechanism? PMID- 20353415 TI - Pacing in severe interatrial conduction block. PMID- 20353416 TI - Proarrhythmic ECG deterioration caused by myocardial ischemia of the conus branch artery in patients with a Brugada ECG pattern. AB - The Brugada-type electrocardiogram (ECG) is characterized by ST-segment elevation in the right precordial ECG leads and has been reported to have the potential of sudden death. Right ventricular outflow tract supplied from the conus branch of the coronary artery (CB) is considered as the anatomopathologic substrate of Brugada syndrome. We experienced two asymptomatic patients with a saddleback Brugada-type ECG who exhibited a dynamic ECG conversion to a coved type following a ventricular fibrillation/ventricular tachycardia (VT/VF) episode when myocardial ischemia occurred exclusively at the CB. Some types of Brugada syndrome might be caused VT/VF by selective myocardial ischemia at the CB. PMID- 20353417 TI - Electrical storm in Brugada syndrome during pregnancy. AB - Clinical and molecular characterization of the Brugada syndrome has progressed rapidly since its initial description. The role of hormonal changes during pregnancy and postpartum period on the pathogenesis of Brugada syndrome has not been studied. Herein, we describe a case of revelation of Brugada syndrome during pregnancy in a young woman who presented with electrical storm as the first manifestation. Low-dose isoproterenol infusion followed by oral quinidine inhibited the recurrence of ventricular tachyarrhythmia and normalized the electrocardiographic pattern. We emphasize the importance of hormonal changes during pregnancy as a precipitating factor for arrhythmic events in Brugada syndrome. PMID- 20353418 TI - Diurnal heart rate patterns in inappropriate sinus tachycardia. AB - BACKGROUND: Inappropriate sinus tachycardia (IAST) is a supraventricular tachycardia originating from the sinus node. Proposed etiologies for this symptom complex include autonomic dysfunction, abnormal automaticity, or hypersensitivity of the sinus node. METHODS: Patients with IAST were identified by symptomatic tachycardia, with P-wave morphology consistent with origination from a sinus location. A matched set of control subjects was included. Hourly heart rate (HR) was measured as the average HR during each one hour period on an ambulatory 24 hour Holter monitor. Patients were further divided into two subgroups based on average daily HR < or = 80 and >80 bpm. Harmonic analysis was used to evaluate diurnal variation. RESULTS: The mean HR was 86.0 +/- 12.8 beats per minute (bpm) in the IAST group and 73.9 +/- 8.6 bpm in the control group (P = 0.056). There was an increased overall heart rate for the IAST group, which appeared to be more prominent in the morning hours. In the IAST subgroup with average daily HR < or = 80, hourly HR appears similar to controls for the period 8 pm-8 am. However, in the late AM, the IAST group had an increase in HR not seen in the control subjects. In the IAST subgroup with average HR > 80, there appeared to be a fixed difference in HR compared to the control group, without hourly change. CONCLUSIONS: Patients with IAST and elevated average daily HR exhibit normal diurnal variation around a higher mean HR. In contrast, patients with IAST and lower average daily HR had an exaggerated morning rise in HR. These diurnal patterns may be useful to classify the pathophysiology of IAST. PMID- 20353419 TI - Carbon and nitrogen supply to the underground orchid, Rhizanthella gardneri. AB - *Rhizanthella gardneri is a rare and fully subterranean orchid that is presumably obligately mycoheterotrophic. R. gardneri is thought to be linked via a common mycorrhizal fungus to co-occurring autotrophic shrubs, but there is no experimental evidence to support this supposition. *We used compartmentalized microcosms to investigate the R. gardneri tripartite relationship. (13)CO(2) was applied to foliage of Melaleuca scalena plants and [(13)C-(15)N]glycine was fed to the common mycorrhizal fungus, and both sources traced to R. gardneri plants. *In our microcosm trial, up to 5% of carbon (C) fed as (13)CO(2) to the autotrophic shrub was transferred to R. gardneri. R. gardneri also readily acquired soil C and nitrogen (N), where up to 6.2% of C and 22.5% of N fed as labelled glycine to soil was transferred via the fungus to R. gardneri after 240 h. *Our study confirms that R. gardneri is mycoheterotrophic and acquires nutrients via mycorrhizal fungus connections from an ectomycorrhizal autotrophic shrub and directly from the soil via the same fungus. This connection with a specific fungus is key to explaining why R. gardneri occurs exclusively under certain Melaleuca species at a very limited number of sites in Western Australia. PMID- 20353420 TI - Transdifferentiation of adipose-derived stem cells into hepatocytes: a new approach. AB - BACKGROUND: Several studies have demonstrated techniques in differentiating human adipose-derived stem cells (hADSCs) into hepatocytes. Unfortunately, transdifferentiation is inefficient, and the function of these induced hepatocyte like cells (which we termed 'iHeps') is low compared with that of real hepatocytes. AIMS: We aimed to identify transcriptional deficiencies in iHeps that are critical to hepatocyte development, which may provide insights into improving the efficiency of transdifferentiation. METHODS: hADSCs were differentiated into iHeps, and iHeps were assayed for hepatocyte-like activity. iHeps were then screened for expression of several growth factors, receptors and transcription factors (TFs) critical to liver development using reverse transcription-polymerase chain reaction (RT-PCR). Deficient TFs were transduced into hADSCs and hepatocyte function was reassessed after hepatic differentiation. RESULTS: Differentiation of hADSCs into iHeps resulted in the upregulation of hepatic proteins. However, the levels of expression of hepatocyte-specific proteins in these iHeps were well below those of Huh 7.5 hepatoma cells, used in comparison. Five developmental TFs were notably absent on the RT-PCR screen. Lentiviral transduction of these TFs into hADSCs followed by culture in hepatocyte induction medium resulted in increased albumin expression compared with untransduced hADSCs treated in a parallel fashion. CONCLUSIONS: These five missing TFs are known to regulate hepatocyte differentiation and some are required to establish the competence of the foregut endoderm. Presumably due to their mesenchymal lineage, hADSCs do not express these endodermal TFs and are not fully competent to respond to critical developmental signals. Supplementation of these TFs may induce competency and enhance the differentiation of hADSCs into hepatocytes. PMID- 20353422 TI - Soluble gp130 promotes intestinal epithelial hyperplasia during reovirus infection. AB - Soluble gp130 (sgp130) has been shown to suppress the inflammatory response of autoimmune pathologies; however, its effects on virus infection are not known. Here, we report that intraperitoneal treatment of mice with sgp130-Fc fusion protein at the time of oral reovirus serotype 3 infection resulted in altered morphopathological changes that were evident by less shortening of intestinal villi length and crypt depth after infection. That the effect mediated by sgp130 treatment was due to an increase in intestinal crypt cell proliferation was demonstrated by an increase in the number of crypt mitotic figures. This was further confirmed by increased immunoreactivity to the Cdc47 proliferation associated antigen in crypts of sgp130-treated virus-infected mice compared to infected non-treated mice. These findings suggest that sgp130 may have a beneficial effect during intestinal virus infection by disrupting interleukin-6 trans-signalling, thereby reducing the local inflammatory response. PMID- 20353421 TI - Proteomic analysis of osteogenic sarcoma: association of tumour necrosis factor with poor prognosis. AB - A significant proportion of patients with osteogenic sarcoma die from lung metastasis within 5 years of diagnosis. Molecular signatures that predict pulmonary metastasis from primary osteogenic sarcoma and identify those patients at risk would be clinically useful as prognostic markers. Protein expression profiles of two clonally related murine osteogenic sarcoma cell lines with low (K12) and high (K7M2) metastatic potential were compared using two different proteomic technologies, two-dimensional difference gel electrophoresis and cell profiling by matrix-assisted laser desorption/ionization mass spectrometry. Interrogation of a molecular pathways network database suggested several additional candidate molecules that potentially predict metastatic potential of primary osteogenic sarcoma. Two such proteins, macrophage migration inhibitory factor and tumour necrosis factor were selected for further validation studies. Western blots confirmed increased expression of both cytokines in K7M2 cells compared to K12 cells. Levels of migration inhibitory factor and tumour necrosis factor were semi-quantitatively measured in human osteogenic sarcoma samples by immunohistochemistry and were correlated with clinicopathologic parameters and patient outcomes. Multivariate survival analysis demonstrated that tumour necrosis factor expression in chemotherapy naive osteogenic sarcoma is an independent prognostic factor for overall and metastasis-free survival. No significant differences in adverse outcomes were observed based on macrophage migration inhibitory factor expression. PMID- 20353423 TI - Ischaemia-reperfusion modulates inflammation and fibrosis of skeletal muscle after contusion injury. AB - Regeneration of skeletal muscle following injury is dependent on numerous factors including age, the inflammatory response, revascularization, gene expression of myogenic and growth factors and the activation and proliferation of endogenous progenitor cells. It is our hypothesis that oxidative stress preceding a contusion injury to muscle modulates the inflammatory response to inhibit muscle regeneration and enhance fibrotic scar formation. Male F344/BN rats were assigned to one of four groups. Group 1: uinjured control; Group 2: ischaemic occlusion of femoral vessels for 2 h followed by reperfusion (I-R); Group 3: contusion injury of the tibialis anterior (TA); Group 4: I-R, then contusion injury. The acute inflammatory response (8 h, 3 days) was determined by expression of the chemokine CINC-1, TGF-beta1, IFN-gamma and markers of neutrophil (myeloperoxidase) and macrophage (CD68) activity and recruitment. Acute oxidative stress caused by I-R and/or contusion, was determined by measuring GP91(phox) and lipid peroxidation. Muscle recovery (21 days) was assessed by examining the fibrosis after I-R and contusion injuries to the TA with Sirius Red staining and quantification of collagen I expression. Consistent with our hypothesis, I-R preceding contusion increased all markers of the acute inflammatory response and oxidative stress after injury and elevated the expression of collagen. We conclude that ischaemia induced oxidative stress exacerbated the inflammatory response and enhanced fibrotic scar tissue formation after injury. This response may be attributable to increased levels of TGF-beta1 and diminished expression of IFN-gamma in the ischaemic contused muscle. PMID- 20353424 TI - Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity. AB - The present study examined the response of the prostate epithelium of senescent gerbils submitted to orchiectomy and with or without steroidal blockade. Animals were divided into five groups, all surgically castrated except the control group composed of intact animals. In the experimental groups, doses of flutamide and/or tamoxifen were applied for 1, 3, 7 and 30 days postcastration. The structural methods applied reveal that castration, whether associated or not with anti steroidal drugs, promoted short- and long-term decrease in wet and relative weights of the prostate. The quantitative decline of epithelial compartment proportion observed at the end of treatment was due to the sum of slight changes in the epithelium and lumen. The apoptotic index had risen significantly at 1 day and declined at 7 days postcastration. Androgen receptor (AR) expression decreased after 3 days of hormonal ablation, coinciding with the highest levels of apoptosis and cell proliferation observed in all treated groups. The majority of cells remained differentiated in all groups due to CK 8/18 expression. Some animals remained with injuries such as carcinomas and adenocarcinomas after hormonal ablation. In the latter a mixture of AR-positive and AR-negative cells was identified. Microinvasive carcinomas found in the group treated for 30 days consisted of PCNA-positive, inflammatory and non-proliferating cells. Low apoptosis incidence and bcl-2 positive cells were observed in these lesions. The treatments promoted a reduction of lesions in older gerbils, but treatment resistant tumours will improve understanding of the events that lead to hormone resistance. PMID- 20353425 TI - Effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits. AB - This study was designed to evaluate the effects of the combined treatment with an anti-coagulant (enoxaparin) agent and a lipid-lowering agent (lovastatin) on prevention or decrease in the occurrence of steroid-induced osteonecrosis in rabbits. A total of 112 rabbits, which were injected intramuscularly with 20 mg/kg of methylprednisolone acetate were divided into four groups and treated as follows: one group received enoxaparin combined with lovastatin (EL; n = 30), another received enoxaparin alone (EA; n = 28), another received lovastatin alone (LA; n = 28) and the last received no treatment (non-prophylactic; NP, n = 26). Haematological examination for serum lipid levels and prothrombin time was carried out and both femora and humeri were examined histopathologically for the presence of osteonecrosis (ON) before injection and at 2, 4, 8 and 12 weeks after the injection. The incidence of ON in the EL group (15%) was significantly lower than that observed in the NP group (68%). The incidence in the EA and LA groups was also significantly lower than that in the NP group (31%, 35%vs. 68%). The fat cell sizes of the bone marrow in both EL (46.49 +/- 1.27 microm) and LA (50.8 +/- 2.31 microm) groups were lower than in the NP group (59.89 +/- 6.33 microm). The prothrombin time was prolonged and plasma lipid levels were reduced in the EL group during the study. Combination treatment with an anti-coagulant agent and a lipid-lowering agent can reduce the incidence of steroid-induced ON in rabbits. Future evaluation in clinical practice is necessary. PMID- 20353426 TI - The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1 oxide-induced carcinogenesis model. AB - The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells. PMID- 20353427 TI - Long-term changes in the ipsilateral substantia nigra after transient focal cerebral ischaemia in rats. AB - Transient focal cerebral ischaemia can cause neuronal damage in remote areas, including the ipsilateral thalamus and subsutantia nigra, as well as in the ischaemic core. In the present study, we investigated long-term changes in the ipsilateral substantia nigra from 1 up to 20 weeks after 90 min of transient focal cerebral ischaemia in rats, using tyrosine hydroxylase (TH), neuronal nuclei (NeuN), Iba-1, glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) immunostaining. These results show that transient focal cerebral ischaemia in rats can cause a severe and prolonged neuronal damage in the ipsilateral striatum. Our results with TH and NeuN immunostaining also demonstrate that the atrophy of the ipsilateral substantia nigra after transient focal cerebral ischaemia was not static but progressive. Furthermore, our double labelled immunohistochemical study suggests that BDNF released by GFAP-positive astrocytes may play a key role in the survival of dopaminergic neurones in the ipsilateral substantia nigra at the chronic stage after transient focal cerebral ischaemia, although the areas of the ipsilateral substantia nigra are decreased progressively after ischaemia. Thus our study provides further valuable information for the pathogenesis of neuronal damage after transient focal cerebral ischaemia. PMID- 20353428 TI - Molecular monitoring of fungal communities in air samples by denaturing high performance liquid chromatography (D-HPLC). AB - AIMS: To describe a new molecular technique for the assessment of fungal diversity in the air. METHODS AND RESULTS: Air samples were collected every week in a henhouse in France during a 15-week period. After air sampling, the collecting membrane was diluted, and the liquid was used for subsequent cultivation and molecular analysis: PCR-temperature temporal gradient electrophoresis (TTGE), which has already been used for the identification of fungal species in air samples and PCR-denaturing high-performance liquid chromatography (D-HPLC), a new technique for the analysis of complex microbial populations. D-HPLC profiles were reproducible from run-to-run, and several fungal organisms could be identified at the species level by sequencing. CONCLUSIONS: PCR-D-HPLC enabled the identification of fungal species (both Ascomycota and Basidiomycota) that may be encountered in air. The new technique allowed the detection of more fungal species than did the PCR-TTGE technique. However, some fungal species were detected only by PCR-TTGE, suggesting that PCR D-HPLC and PCR-TTGE are complementary. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR D-HPLC represents a considerable saving in time over currently available procedures for detection and identification of fungal organisms in air. However, the fungal diversity detected by PCR-D-HPLC or by PCR-TTGE was lower than that revealed by culture. PMID- 20353429 TI - Isolation and selection of coliphages as potential biocontrol agents of enterohemorrhagic and Shiga toxin-producing E. coli (EHEC and STEC) in cattle. AB - AIMS: To isolate, characterize and select phages as potential biocontrol agents of enterohemorrhagic and Shiga toxin-producing Escherichia coli (EHEC and STEC) in cattle. METHODS AND RESULTS: Sixteen STEC and EHEC coliphages were isolated from bovine minced meat and stool samples and characterized with respect to their host range against STEC, EHEC and other Gram-negative pathogens; their morphology by electron microscopy; the presence of the stx1, stx2 and cI genes by means of PCR; RAPD and rep-PCR profiles; plaque formation; and acid resistance. Six isolates belonged to the Myoviridae and 10 to the Podoviridae families. The phages negative for stx and cI that formed large, well-defined plaques were all isolated using EHEC O157:H7 as host. Among them, only CA911 was a myophage and, together with CA933P, had the broadest host range for STEC and EHEC; the latter phage also infected Shigella and Pseudomonas. Isolates CA911, MFA933P and MFA45D differed in particle morphology and amplification patterns by RAPD and rep-PCR and showed the highest acidity tolerance. CONCLUSIONS: Myophage CA911 and podophages CA933P, MFA933P and MFA45D were chosen as the best candidates for biocontrol of STEC and EHEC in cattle. SIGNIFICANCE AND IMPACT OF THE STUDY: This work employs steps for a rational selection and characterization of bacteriophages as therapeutic agents. This report constitutes the first documentation of STEC and EHEC phages isolated in Argentina and proposes for the first time the use of rep-PCR as a complement of RAPD on DNA fingerprinting of phages. PMID- 20353430 TI - The effect of Pediococcus acidilactici on the gut microbiota and immune status of on-growing red tilapia (Oreochromis niloticus). AB - AIM: To assess Pediococcus acidilactici as a dietary supplement for on-growing red tilapia (Oreochromis niloticus). METHODS AND RESULTS: Tilapia were fed either a control diet or control diet supplemented with Ped. acidilactici at 10(7) CFU g(-1) for 32 days. Ped. acidilactici colonized the intestinal tract and significantly affected the intestinal microbial communities. PCR-DGGE revealed direct antagonism of gastric Ped. acidilactici with an endogenous uncultured bacterium during a period of reverting to nonsupplemented feeding. Light microscopy revealed that gut integrity and leucocyte levels were unaffected by Ped. acidilactici; however, blood leucocyte levels and serum lysozyme activity were elevated after 14-days' feeding. No significant improvements in growth performance were observed at the end of the trial (day 32), but survival was significantly higher in the probiotic group. CONCLUSIONS: The study demonstrates that oral supplementation of Ped. acidilactici modulates intestinal bacterial communities in on-growing red tilapia and also stimulates some aspects of the nonspecific immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge this is the first study assessing the effects of probiotics on the gut microbiota of tilapia using culture-independent methods. Such methods are crucial to understand the mechanisms which underpin and mediate host benefits. PMID- 20353431 TI - Long-term cost-effectiveness of weight management in primary care. AB - BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12 month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month attenders were assumed thereafter to rise at the background rate, 4 kg below non intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits. PMID- 20353432 TI - Revisiting the role of ergots in the treatment of migraine and headache. AB - The harmful side effects of the ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential ergot side effects, but may also account for efficacy. The role of ergots in headache should be revisited, especially in view of newer ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroergotamine. Redefining where in the headache treatment spectrum ergots belong and deciding when they may be the optimal choice of treatment is necessary. PMID- 20353433 TI - Episodic cluster headache: NREM prevalence of nocturnal attacks. Time to look beyond macrostructural analysis? AB - BACKGROUND: A high prevalence of nocturnal sleep-related attacks is reported in patients with cluster headache (CH). Episodic CH is considered closely related to rapid eye movement (REM) sleep. OBJECTIVE: The aim of this study was to analyze the relationships between episodic CH attacks and sleep macrostructure. METHODS: Data were obtained by means of 24-hour continuous ambulatory polysomnography (PSG) capturing CH attacks in 4 out of 7 episodic CH patients (all males; mean age 38.4 +/- 9.2 years) studied. RESULTS: Eight CH attacks were captured during the PSG monitoring; 5 arose from sleep: 4 from non-rapid eye movement (NREM) sleep (stage 2 NREM), and 1 from REM sleep. One patient experienced CH attacks during both NREM and REM sleep in the same night. CONCLUSIONS: In the light of previous literature findings, the prevalence of NREM-related episodic CH attacks observed, and the finding of attacks arising during both REM and NREM sleep in the same subject, suggest that the relationship between CH and sleep stages is heterogeneous, and the existence of a specific macrostructural pattern associated with episodic CH attacks appears to be uncertain. A more comprehensive approach taking into account the microstructure of NREM and REM sleep is expected to provide more in depth information about the pathophysiology of CH, whose complexity might overcome the simplistic dichotomy of REM/NREM staging. PMID- 20353434 TI - Changes in salivary prostaglandin levels during menstrual migraine with associated dysmenorrhea. AB - OBJECTIVE: To measure prostaglandin levels in the saliva of individuals during menstrual migraine associated with dysmenorrhea (MMaD) and in response to treatment with a single tablet combination of sumatriptan succinate and naproxen sodium. BACKGROUND: Prostaglandins are thought to play a role in MMaD as elevated serum prostaglandin levels have been reported during attacks of menstrual migraine and are increased in the menstrual fluid of women with dysmenorrhea. While triptans are the primary line of migraine treatment, nonsteriodal anti inflammatory drugs are the most commonly prescribed therapy for dysmenorrhea symptoms. Data from recent clinical studies have provided evidence that treatment with a single tablet combination of sumatriptan and naproxen sodium is an effective abortive therapy for attacks of MMaD. METHODS: Women diagnosed with MMaD were treated with a sumatriptan succinate and naproxen sodium single tablet combination or placebo at time of migraine attack. Saliva samples were collected at time of attack as well as 2 and 4 hours after treatment. PGD(2), PGE(2), PGF(2), PGI(2), and TXA(2) levels were determined by enzyme-linked immunosorbent assay. RESULTS: Elevated levels of PGD(2), PGF(2), and TXA(2) at 2 and 4 hours and PGE(2) at 4 hours were found in saliva obtained from placebo subjects when compared with onset of attack levels. However, in subjects treated with a single tablet combination of sumatriptan and naproxen sodium, the levels of PGD(2), PGF(2), and PGE(2) were not elevated at either time point while TXA(2) levels were still elevated at 4 hours. CONCLUSIONS: Data from this pilot study provide evidence that saliva levels of several prostaglandins increase during attacks of MMaD and that treatment with a single tablet combination of sumatriptan and naproxen sodium prevents elevation of prostaglandin levels. PMID- 20353435 TI - Treatment of post-dural puncture headache with bilateral greater occipital nerve block. AB - (Headache 2010;50:869-881) Epidural blood patch is an effective treatment with a low complication rate. It is also an invasive method that can cause permanent neurological sequelae such as early and late back pain, radiculopathy, spinal subdural hematoma, spinal-epiarachnoid hematoma, intrathecal hematoma, arachnoiditis, and infection. We report a case in which a postdural puncture headache resolved within 2 minutes of a greater occipital nerve block, a minimally invasive and easy procedure with a low complication rate. This case report suggests that a greater occipital nerve block may be a successful alternative treatment for patients with post-dural puncture headache. PMID- 20353436 TI - Epidermal growth factor's activation of Ras is inhibited by four cardiac hormones. AB - BACKGROUND: Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, have anticancer effects in vitro and in vivo. Epidermal growth factor's mechanism of cancer formation involves the activation of Ras. MATERIALS AND METHODS: These four cardiac hormones were evaluated for their ability to inhibit mitogen (epidermal growth factor) activation of Ras. RESULTS: Epidermal growth factor increased the activation of Ras by 68%, 85% and 90% at its 1, 2 and 5 ng mL(-1) concentrations. Vessel dilator, long-acting natriuretic peptide, atrial natriuretic peptide and kaliuretic peptide inhibited 5 ng mL(-1) epidermal growth factor's stimulation of Ras by 73%, 79%, 33% and 45%, respectively, at their 1 microM concentrations. Their effects on epidermal growth factor's activation of Ras were specific with addition of the cardiac hormones' respective antibodies (5 microM) blocking 95%, 93%, 100% and 100% (P < 0.001 for each) of their ability to inhibit epidermal growth factor's stimulation of Ras. CONCLUSIONS: Four cardiac hormones specifically inhibit epidermal growth factor's activation of Ras. This investigation would suggest that these cardiac hormones' anticancer effects involve the inhibition of mitogens such as epidermal growth factor's ability to activate Ras as well as inhibiting unstimulated basal activity of Ras. PMID- 20353437 TI - Regulation of adipokine production in human adipose tissue by propionic acid. AB - BACKGROUND: Dietary fibre (DF) has been shown to be protective for the development of obesity, insulin resistance and type 2 diabetes. Short-chain fatty acids, produced by colonic fermentation of DF might mediate this beneficial effect. Adipose tissue plays a key role in the regulation of energy homeostasis, therefore, we investigated the influence of the short-chain fatty acid propionic acid (PA) on leptin, adiponectin and resistin production by human omental (OAT) and subcutaneous adipose tissue (SAT). As PA has been shown to be a ligand for G protein coupled receptor (GPCR) 41 and 43, we investigated the role of GPCR's in PA signalling. MATERIALS AND METHODS: Human OAT and SAT explants were obtained from gynaecological patients who underwent surgery. Explants were incubated for 24 h with PA. Adipokine secretion and mRNA expression were determined using ELISA and RT-PCR respectively. RESULTS: We found that PA significantly stimulated leptin mRNA expression and secretion by OAT and SAT, whereas it had no effect on adiponectin. Furthermore, PA reduced resistin mRNA expression. Leptin induction, but not resistin reduction, was abolished by inhibition of Gi/o-coupled GPCR signalling. Moreover, GPCR41 and GPCR43 mRNA levels were considerably higher in SAT than in OAT. CONCLUSIONS: We demonstrate that PA stimulates expression of the anorexigenic hormone leptin and reduces the pro-inflammatory factor resistin in human adipose tissue depots. This suggests that PA is involved in regulation of human energy metabolism and inflammation and in this way may influence the development of obesity and type 2 diabetes. PMID- 20353439 TI - Why are metabolic scaling exponents so controversial? Quantifying variance and testing hypotheses. AB - The metabolic theory of ecology links physiology with ecology, and successfully predicts many allometric scaling relationships. In recent years, proponents and critics of metabolic theory have debated vigorously about the scaling of metabolic rate. We show that the controversy arose, in part, because researchers examined the mean exponent separately from the variance. We estimate both quantities simultaneously using linear mixed-effects models and data from 1242 animal species. Metabolic rate scaling converges on the predicted value of 3/4 but is highly heterogeneous: 50% of orders lie outside the range 0.68-0.82. These findings are robust to several forms of statistical uncertainty. We then test competing hypotheses about the variation. Metabolic theory is currently unable to explain differences in scaling among orders, but the patterns are not consistent with competing explanations either. We conclude that current theories are inadequate to explain the full range of metabolic scaling patterns observed in nature. PMID- 20353438 TI - Pseudomonas fluorescens orchestrates a fine metabolic-balancing act to counter aluminium toxicity. AB - Aluminium (Al), an environmental toxin, is known to disrupt cellular functions by perturbing iron (Fe) homeostasis. However, Fe is essential for such metabolic processes as the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, the two pivotal networks that mediate ATP production during aerobiosis. To counter the Fe conundrum induced by Al toxicity, Pseudomonas fluorescens utilizes isocitrate lyase and isocitrate dehydrogenase-NADP dependent to metabolize citrate when confronted with an ineffective aconitase provoked by Al stress. By invoking fumarase C, a hydratase devoid of Fe, this microbe is able to generate essential metabolites. To compensate for the severely diminished enzymes like Complex I, Complex II and Complex IV, the upregulation of a H(2)O-generating NADH oxidase enables the metabolism of citrate, the sole carbon source via a modified TCA cycle. The overexpression of succinyl-CoA synthetase affords an effective route to ATP production by substrate-level phosphorylation in the absence of O(2). This fine metabolic balance enables P. fluorescens to survive the dearth of bioavailable Fe triggered by an Al environment, a feature that may have potential applications in bioremediation technologies. PMID- 20353440 TI - Outcomes in achalasia from a surgical unit where pneumatic dilatation is first line therapy. AB - The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia. PMID- 20353441 TI - The prevalence of Barrett's esophagus in the US: estimates from a simulation model confirmed by SEER data. AB - Barrett's esophagus (BE) is the precursor and the biggest risk factor for esophageal adenocarcinoma (EAC), the solid cancer with the fastest rising incidence in the US and western world. Current strategies to decrease morbidity and mortality from EAC have focused on identifying and surveying patients with BE using upper endoscopy. An accurate estimate of the number of patients with BE in the population is important to inform public health policy and to prioritize resources for potential screening and management programs. However, the true prevalence of BE is difficult to ascertain because the condition frequently is symptomatically silent, and the numerous clinical studies that have analyzed BE prevalence have produced a wide range of estimates. The aim of this study was to use a computer simulation disease model of EAC to determine the estimates for BE prevalence that best align with US Surveillance Epidemiology and End Results (SEER) cancer registry data. A previously developed mathematical model of EAC was modified to perform this analysis. The model consists of six health states: normal, gastroesophageal reflux disease (GERD), BE, undetected cancer, detected cancer, and death. Published literature regarding the transition rates between these states were used to provide boundaries. During the one million computer simulations that were performed, these transition rates were systematically varied, producing differing prevalences for the numerous health states. Two filters were sequentially applied to select out superior simulations that were most consistent with clinical data. First, among these million simulations, the 1000 that best reproduced SEER cancer incidence data were selected. Next, of those 1000 best simulations, the 100 with an overall calculated BE to Detected Cancer rates closest to published estimates were selected. Finally, the prevalence of BE in the final set of best 100 simulations was analyzed. We present histogram data depicting BE prevalences for all one million simulations, the 1000 simulations that best approximate SEER data, and the final set of 100 simulations. Using the best 100 simulations, we estimate the prevalence of BE to be 5.6% (5.49-5.70%). Using our model, an estimated prevalence for BE in the general population of 5.6% (5.49-5.70%) accurately predicts incidence rates for EAC reported to the US SEER cancer registry. Future clinical studies are needed to confirm our estimate. PMID- 20353442 TI - Effect of a selective neutrophil elastase inhibitor on early recovery from body water imbalance after transthoracic esophagectomy. AB - The objective of the study was to evaluate the efficacy of sivelestat, a selective neutrophil elastase inhibitor, on body fluid balance after transthoracic esophagectomy. Esophagectomy with elective lymphadenectomy may induce excessive release of neutrophil elastase, which then promotes vascular permeability and an excessive water shift from the intravascular space to the peripheral compartment. Body fluid imbalance after esophagectomy often leads to circular instability, a decrease of urine output, and a delay in the shift to a diuretic state. The study was designed as a case-control study with a historical control group. A retrospective analysis was performed to examine our hypothesis that sivelestat improves abnormal body fluid retention and prevents subsequent pulmonary complications. To reveal the direct influence of sivelestat on the postoperative course, we avoided using steroids or other diuretic agents. Eighty eight patients who underwent thoracic esophagectomy with extended lymphadenectomy from 2000 to 2008 were divided into two groups: those treated from 2003 to 2008, who all received postoperative administration of sivelestat (n=60); and those treated from 2000 to 2002, who did not receive sivelestat and were used as the control group (n=28). Both groups received fluid management using the same protocol. The time to reach a diuretic state, time until extubation of the tracheal tube, and development of delayed respiratory dysfunction were compared between the groups using univariate and multivariate analysis. The time until a shift to a diuretic state was significantly shorter after treatment with sivelestat (p<0.0001) and with a shorter operation time (p<0.0001). The tracheal tube was extubated significantly earlier in the sivelestat group (p<0.0001) and the incidence of delayed respiratory dysfunction was also significantly lower (p=0.0028) in this group. Multivariate logistic regression analysis showed that a delay in a shift to a diuretic state was a strong independent risk factor for the time to tracheal extubation (odds ratio 2.539, p=0.0056) and occurrence of delayed respiratory dysfunction (odds ratio 1.989, p=0.0104). Sivelestat treatment was not independently associated with reduced pulmonary complications, but the diuretic state was strongly regulated by sivelestat treatment (odds ratio 0.044, p=0.0003). Thus, administration of sivelestat has a beneficial influence on recovery from body water imbalance through a more rapid return to a diuretic state after esophagectomy, which contributes to prevention of subsequent pulmonary complications. PMID- 20353443 TI - Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease. AB - Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett's esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett's and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study. PMID- 20353444 TI - Esophageal dilation: simple and effective treatment for adults with eosinophilic esophagitis and esophageal rings and narrowing. AB - The goal of this article is to present the results of the long-term treatment with esophageal dilation of a consecutive series of adults with eosinophilic esophagitis (EoE). EoE in adults is a disease of middle aged white males, with recurrent food impactions and dysphagia. The exact treatment of EoE is unknown due to the uncertainty of the pathogenesis. Currently, the long-term follow-up of adult EoE patients is limited. Sixteen consecutive adult patients (12 males/4 females between ages 27 and 58 years) with EoE underwent a detailed history and baseline upper gastrointestinal endoscopy (EGD) with multiple esophageal biopsies. Thirteen had esophageal dilation. Fifteen were on proton pump inhibitor (PPI) therapy. After dilation, one patient was treated with a restrictive diet. One patient took prn fluticasone. Most of the patients had allergy testing for food and aeroallergens. Follow-up evaluation with similar testing was on average 22 months (range: 12-40 months). Six patients were not available for follow-up. None of the remaining 10 patients had a food impaction; one required further esophageal dilation. Only two patients had intermittent dysphagia. The average dysphagia score decreased from 2.1 to 0.3 (P < 0.002). The average number of eosinophils at follow-up was not significantly different from baseline (120 eosinophils/HPF proximally and 165 eosinophils/HPF distally (P= 0.75). The gross endoscopy findings were unchanged in all patients except one who normalized. A total of 62% and 75% of patients had positive tests for aeroallergens and food allergens, respectively. Over an average of two years, esophageal dilation provided excellent symptomatic relief among 10 adult EoE patients despite no improvement in the mucosal eosinophilia or gross endoscopic appearance. PMID- 20353446 TI - A case of esophageal leiomyoma causing left atrial compression. PMID- 20353445 TI - Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis. AB - Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 +/- 2.2/HPF, EoE 19.8 +/- 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 +/- 0.7 and 74.9 +/- 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 +/- 0.16/HPF) and EoE (0.09 +/- 0.04; P = 0.07). Eight of the 39 RE specimens had >or=50 lymphocytes in >or=1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = 0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 +/- 1.3 vs 22.2 +/- 2.3/HPF; P = 0.030) and eosinophils (55.6 +/- 5.2 vs 76.0 +/- 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE. PMID- 20353447 TI - Temporary self-expanding metallic stents and pneumatic dilation for the treatment of achalasia: a prospective study with a long-term follow-up. AB - The present study compares the efficacy of a self-expanding metallic stent (SEMS, diameter of 30 mm) and pneumatic dilation for the long-term clinical treatment of achalasia. A total of 155 patients diagnosed with achalasia were allocated for pneumatic dilation (n= 80, group A) or a temporary, 30-mm diameter SEMS (n= 75, group B). The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after placement. Data on clinical symptoms, complications, and long-term clinical outcomes were collected, and follow-up observations were performed at 6 months and at 1, 3-5, 5-8, 8-10, and >10 years, postoperatively. Pneumatic dilation and stent placement were technically successful in all of the patients. There were no significant differences in technique success, 30-day mortality, or complications between the two groups. The clinical remission rate in group A was significantly lower than that in group B at 1, 1-3, 3-5, 5-8 and, >10 years (P < 0.05), while the cumulative clinical failure rate in group A (66%, 53/80) was higher than that in group B (92%, 6/75). The mean primary patency in group B was significantly longer than that in group A (4.2 vs 2.1 years, respectively; P < 0.001). A temporary, 30-mm diameter SEMS was associated with a better long-term clinical efficacy in the treatment of patients with achalasia as compared with treatment with pneumatic dilation. PMID- 20353448 TI - Why is there heterogeneity in the effect of dental checkups? Assessing cohort effect. AB - OBJECTIVES: To evaluate age as a potential effect modifier of the relation between frequency of dental check-up and oral health. METHODS: Data from a Brazilian oral health survey carried out in 2002-2003 was obtained for three age groups: 15-19-year-old (n=16411); 35-44-year-old (n=13269); and 65-74-year-old (n=5 300). Individuals were examined by dentists and followed to an interview. Self-reported time since last dental visit was measured as 'less than 1 year'; 'from 1 to 2 years'; '3 or more years' or 'never'. Outcomes modelled with negative binomial regression were DMFT index and DT, MT and FT. RESULTS: Visiting the dentist more recently was associated with fewer teeth with untreated dental caries (DT) and more teeth with fillings (FT) across all age groups. Among the 15 19-year-old, the longer the time since last visit the lower the DMFT and MT. On the other hand, among the 35-44 and the 65-74-year-old the longer the time since last dental visit the higher the DMFT and MT, though this trend reverted in the 'never visited' group. CONCLUSIONS: Age modified the effect of dental visits on DMFT and MT. In younger cohorts, the low frequency of dental check-up among those with good oral health may reflect the fact that these young people do not feel they need to go to the dentist very often, while in older cohorts, the current low frequency of dental check-up associated with bad oral health may be a reflection of a lifetime of high disease incidence coupled with access barriers. Questions regarding the time and frequency of dental visits may capture different dimensions of utilization of dental services, and so pooled estimates are not appropriate. Our results may help explaining contrasting results in previously published studies. PMID- 20353449 TI - Assessing the level of agreement between the self- and interview-administered Child-OIDP. AB - OBJECTIVE: To assess the level of agreement between the self- and interviewer administered Child version of the Oral Impacts on Daily Performances (Child-OIDP) index. METHODS: This was a randomised study in 177 children aged 10-13 years from Granada (Spain). All children completed both administration modes of the Child OIDP; half the sample received the interviewer-administered version first (n = 90), and the other half the self-administered version first (n = 87). This was done to address potential order effects due to the sequential administration of both instruments. The level of agreement between both modes of administration was assessed with the Bland and Altman method for the Child-OIDP score and Kappa for the prevalence of oral impacts. RESULTS: The two groups did not differ in their socio-demographic characteristics or self-perceived oral health measures. No order effects were found. There was no significant difference between the two modes of administration in terms of the overall score and prevalence of oral impacts (P > or = 0.784 in both cases). The mean difference in Child-OIDP scores was 0.03 (95% CI = -0.29 to 0.35) and the 95% limits of agreement were -6.32 and 4.93. Kappa value for the prevalence of impacts was 0.92. CONCLUSIONS: The self- and interviewer-administered Child-OIDP had a high level of agreement, irrespectively of whether the overall score or the prevalence of oral impacts was used to describe children's quality of life. PMID- 20353450 TI - Independent predictors of satisfaction in impacted third molar surgery patients. AB - OBJECTIVES: Patient satisfaction and dissatisfaction are critical dimensions leading to favorable or unfavorable treatment outcomes. Although impacted third molar (ITM) surgery is one of the most common dental surgical procedures, it is a challenging operation because of numerous potential complications and patients generally suffer from severe psychosomatic symptoms as a result of severe perioperative anxiety. We hypothesize that multiple independent factors, including perioperative anxiety and various postoperative complications, affect satisfaction of the ITM surgery patients. METHODS: Survey data from 219 participants encompassed basic patient demographic traits, difficulty of surgery, perioperative anxiety, pain sensation and common postoperative complications. The t-test and one-way anova with Duncan's multiple-range tests were applied to detect differences in mean values of perioperative anxiety, perioperative pain sensation and satisfaction based on basic demographic characteristics and postoperative complications. The significance of postoperative complications according to demographic data and difficulty of extraction was also analyzed. A paired t-test was applied to detect the significance of anxiety level and pain sensation changes over time. Lastly, univariate and multiple stepwise regression analyses were used to analyze the relationships among perioperative anxiety, pain sensation and satisfaction to determine the predictive factor of patient satisfaction. RESULTS: Basic demographic traits proved not to have a direct significant effect on satisfaction in ITM surgery patients, but some demographic factors and difficulty of surgery showed significant relationships with postoperative complications. Univariate analysis revealed that perioperative anxiety, pain sensation, postoperative infection, numbness/paresthesia and ecchymoses have a significant influence on patient satisfaction. In particular, preoperative anxiety level and numbness/paresthesia were independent predictive factors of patient satisfaction upon multivariate analysis. CONCLUSIONS: This study demonstrates that the patients who undergo ITM surgery often have severe anxiety that seriously impacts patient satisfaction and resultant treatment outcomes. In addition, patient satisfaction directly depends on the occurrence of some postoperative complications. Appreciation of these predictive factors and increasing patient satisfaction may help clinicians to provide optimal care for ITM surgery patients. PMID- 20353451 TI - Distribution of orthodontic services in Norway. AB - BACKGROUND AND OBJECTIVES: There is a lack of studies that have evaluated how different ways of organizing and financing orthodontic services perform with respect to access to care, and the cost of care. In Norway, orthodontic services for children and adolescents are partly financed by the state, and the size of the state subsidy depends on the severity of the malocclusion. Orthodontists have the freedom to establish a practice where they wish. The aim of this study was to examine whether there are inequalities with respect to access to orthodontic services in Norway, and to study the development of costs of the services from 2004 to 2007. METHODS: Data on mean waiting time for starting treatment and working hours in practice were collected using a questionnaire that was sent to all the orthodontists in the country (n = 165). The response rate was 74%. The number of patients who received treatment according to different criteria of need was recorded from data in each practice. Information about the development of costs for orthodontic treatment was obtained from the National Insurance Administration. RESULTS: In almost all the areas, waiting time for starting treatment was within clinically acceptable limits, and there were only small differences in supply of orthodontic treatment in different areas. Patients with the greatest need were given priority over patients with the least need, which is in line with the aims of the authorities. In 2007 the reimbursements for orthodontic treatment from the National Insurance Administration amounted to Euro 48 million. In deflated prices this was virtually the same amount as in 2004. CONCLUSION: Our results show that the combination of public funding and freedom to establish a practice ensures that services are available for the individuals who are most in need of treatment. The authorities also have control over costs. The experiences from the orthodontic services in Norway are useful for policymakers in other countries. In particular, an important finding is that an orthodontic service where the state subsidy depends on the severity of the malocclusion can secure both equal access to the services and contain costs. PMID- 20353452 TI - Predicting tooth loss for older adults with special needs. AB - OBJECTIVES: Older Adults with Special Needs (OASN) have more oral health needs compared with healthy, independent elders. Currently, little is known about tooth loss, a key indicator of oral function loss, among OASN. Risk assessment is primarily based on clinical experience rather than scientific evidence, raising concerns for quality of care. The study's objective was to develop an evidence based model to quantitatively predict tooth loss for OASN. METHODS: Four hundred ninety-one dentate older adults, including 235 from long-term care facilities, were retrospectively recruited. Subjects were treated and brought to a state of oral health before enrollment. Medical and dental assessments were abstracted from dental records and used to predict risk of tooth loss. Tooth loss events were recorded for subjects during follow-up. Multivariate negative-binomial regression was used, starting with 27 risk factors and removing variables using Akaike's Information Criterion. Pearson's correlation was then conducted to evaluate the overall fit of the final fitted model. RESULTS: The final fitted model included eight predictors. Among them, age, number of decayed/broken teeth at arrival, anticholinergic burden of medications and physical mobility were associated with risk of tooth loss in OASN (P <= 0.05). Internal validation indicated satisfactory fit of the final fitted model. CONCLUSION: An evidence based model with eight predictors was developed to quantitatively predict risk of tooth loss for OASN at the individual level. PMID- 20353453 TI - Effects of mixology courses and blood lead levels on dental caries among students. AB - OBJECTIVE: Dental caries can be affected by alcohol consumption. Alcohol consumption also increases blood lead levels (BLLs) in humans and BLLs have been correlated with caries. Culinary students participate in mixology courses on either an elective or a mandatory basis. Therefore, we conducted this study to elucidate the effects of mixology courses and elevated BLLs on dental caries among students. METHODS: This study had a cross-sectional design. We recruited first-year at one hospitality college and one university in southern Taiwan in September 2004. We applied a questionnaire, collected a blood specimen and performed a dental caries examination for each student. The subjects comprised 133 students who had ever participated in a mixology course (>=2 credits) during high school (exposure group) and 160 who had not participated in such a course (control group). RESULTS: Compared with the control group, the exposure group had a higher prevalence of a DMFT index >= 0 (92.5% versus 81.2%, P = 0.005), a higher DMFT index [5.59 +/- 3.53 (mean +/- SD) versus 4.21 +/- 3.64 teeth, P <= 0.001], and a higher BLL (3.12 +/- 1.02 versus 2.67 +/- 0.83 MUg/dl, P = <= 0.001). After adjustment for potential confounders, dental caries was significantly associated with participation in a mixology course. CONCLUSIONS: Alcohol exposure associated with participation in a mixology course may have an effect on caries in students. These findings suggest that occupational safety and health education should be applied to students participating in mixology courses. PMID- 20353455 TI - Efficacy and safety of tacrolimus ointment 0.1% vs. betamethasone 17-valerate 0.1% in the treatment of chronic paronychia: an unblinded randomized study. PMID- 20353456 TI - The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women. AB - OBJECTIVE: To examine the relationship between dietary supplement use during pregnancy and birth outcomes. DESIGN: A prospective birth cohort. SETTING: Leeds, UK. SAMPLE: One thousand two hundred and seventy-four pregnant women aged 18-45 years. METHODS: Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8-12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. MAIN OUTCOME MEASURES: Birthweight, birth centile and preterm birth. RESULTS: Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P = 0.02). CONCLUSIONS: Regular multivitamin mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study's findings need confirming by other cohorts and/or trials in developed countries. PMID- 20353457 TI - A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. AB - OBJECTIVE: To study serial changes in maternal systemic and uterine artery haemodynamics and establish reference ranges for the second half of pregnancy. DESIGN: Prospective longitudinal observational study. SETTING: University hospital in Norway. POPULATION: Low-risk pregnant women. METHODS: Fifty-three low risk pregnancies were evaluated at approximately 4-weekly intervals. Maternal systemic haemodynamics was assessed with impedance cardiography. Uterine artery blood velocity and diameter were measured using Doppler ultrasonography and uterine artery volume blood flow (Q(uta)) was calculated as the product of mean velocity and cross-sectional area of the uterine artery. The fraction of cardiac output (CO) distributed to the uterine circulation was calculated as: Q(uta)/CO x 100. MAIN OUTCOME MEASURES: CO, Q(uta), uterine vascular resistance (R(uta)) and the fraction of CO distributed to the uterine circulation. RESULTS: The CO increased (P = 0.0063) until 34 weeks and remained stable until term. Total Q(uta) increased from 299 to 673 ml/minute and R(uta) halved from 0.26 to 0.13 mmHg/ml/minute (P < 0.0001). The fraction of CO distributed to the uterine circulation increased from 5.6% to 11.7% (P < 0.0001). CONCLUSION: During the second half of pregnancy, Q(uta) and the fraction of maternal CO distributed to the uterine circulation increase approximately two-fold, mainly as a result of decrease in R(uta). PMID- 20353458 TI - A randomised controlled trial of 300 versus 225 IU recombinant FSH for ovarian stimulation in predicted normal responders by antral follicle count. AB - OBJECTIVE: To test the hypothesis that among women predicted to have a normal ovarian response, ovarian stimulation using 300 IU follicle-stimulating hormone (FSH) results in the retrieval of more mature oocytes than 225 IU during in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Prospective randomised controlled study. SETTING: University-based assisted conception unit. POPULATION: A cohort of 131 women predicted to have a normal ovarian response to gonadotrophin stimulation, based on antral follicle count. METHODS: Subjects undergoing their first cycle of IVF/ICSI were randomised to receive a fixed daily dose of 300 (experimental arm) or 225 IU (control arm) of recombinant FSH (Gonal-F). MAIN OUTCOME MEASURES: Number of mature oocytes retrieved and live birth rates. RESULTS: The number (mean +/- standard deviation) of mature oocytes retrieved (8.2 +/- 5.0 versus 9.0 +/- 4.8, for 300 and 225 IU, respectively; P = 0.34) was similar in each group. There were no differences between the 300- and 225 IU arms in live birth rates (31 versus 41%, respectively; P = 0.25), cycle cancellations resulting from insufficient ovarian response (0 versus 6.1%, respectively; P = 0.12), and prevalence of moderate (3.1 versus 3.0, respectively; P = 1.0) and severe (0 versus 1.5%, respectively; P = 1.0) ovarian hyperstimulation syndrome. CONCLUSIONS: The use of a higher daily dose of 300 IU of recombinant FSH for ovarian stimulation does not improve the number of mature oocytes retrieved, or live birth rates, among women with a predicted normal response during conventional IVF/ICSI. PMID- 20353459 TI - Antenatal interventions for overweight or obese pregnant women: a systematic review of randomised trials. AB - BACKGROUND: Overweight and obesity during pregnancy is an increasing health problem. OBJECTIVE: A systematic review to assess the benefits and harms of antenatal dietary or lifestyle interventions for pregnant women who are overweight or obese. SEARCH STRATEGY: The Cochrane Controlled Trials Register(CENTRAL) was searched (last search January 2010). Reference lists of retrieved studies were searched by hand. No date or language restrictions were used. SELECTION CRITERIA: Randomised controlled trials comparing antenatal dietary and/or lifestyle or other interventions with no treatment for overweight or obese women were considered.Studies were evaluated independently for appropriateness for inclusion and methodological quality. The primary outcome was large-for-gestational-age infants. DATA COLLECTION AND ANALYSIS: Nine randomised controlled trials were included involving 743 women who were overweight or obese during pregnancy. Seven trials compared a dietary intervention with standard antenatal care. MAIN RESULTS: There were no statistically significant differences identified between women who received an antenatal intervention and those who did not for the large-for-gestational-age infant outcome (three studies; 366 women; risk ratio 2.02; 95% CI 0.84,4.86) or mean gestational weight gain [four studies; 416 women;weighted mean difference )3.10 kg; 95% CI )8.32, 2.13 (random effects model)]. There were no statistically significant differences identified for other reported outcomes. AUTHOR'S CONCLUSIONS: The effect of providing an antenatal dietary intervention for overweight or obese pregnant women on maternal and infant health outcomes remains unclear. PMID- 20353460 TI - A score regression approach to assess calibration of continuous probabilistic predictions. AB - Calibration, the statistical consistency of forecast distributions and the observations, is a central requirement for probabilistic predictions. Calibration of continuous forecasts is typically assessed using the probability integral transform histogram. In this article, we propose significance tests based on scoring rules to assess calibration of continuous predictive distributions. For an ideal normal forecast we derive the first two moments of two commonly used scoring rules: the logarithmic and the continuous ranked probability score. This naturally leads to the construction of two unconditional tests for normal predictions. More generally, we propose a novel score regression approach, where the individual scores are regressed on suitable functions of the predictive variance. This conditional approach is applicable even for certain nonnormal predictions based on the Dawid-Sebastiani score. Two case studies illustrate that the score regression approach has typically more power in detecting miscalibrated forecasts than the other approaches considered, including a recently proposed technique based on conditional exceedance probability curves. PMID- 20353461 TI - Retransplantation after BK virus nephropathy in prior kidney transplant: an OPTN database analysis. AB - BK virus (BKV) has emerged as a major complication of kidney transplantation. Since June 30, 2004, the OPTN in the USA collects BKV as a primary or secondary cause of graft loss and also if treatment for BK virus (TBKV) is administered. In this study, we determined characteristics of those recipients of repeat kidney transplants from the OPTN database, where either (a) a graft loss occurred between June 30, 2004 and December 31, 2008 and database recorded prior TBKV in that allograft or (b) a graft loss between June 30, 2004 and December 31, 2008 was attributed primarily or secondarily due to BKV. In the study time period, 823 graft losses have occurred where TBKV or graft failure attributable to BKV was reported in prior transplant; of these, 126 have received a retransplant as of June 5, 2009. Induction and maintenance immunosuppression usage mirrored current trends. As of June 5, 2009, 118/126 grafts are still functioning, one graft failure attributed to BKV. TBKV was reported in 17.5% of the retransplants. In the retransplants performed through December 31, 2007, 1-year acute rejection rate was 7%, 1-year and 3-year Kaplan-Meier graft survival rates and median GFR were 98.5%, 93.6%, 65.5 and 68.4 mL/min, respectively. Retransplantation after BKV appears to be associated with good results. PMID- 20353463 TI - A pitfall in the current kidney allocation process using calculated PRA(CPRA) in patients undergoing desensitization. PMID- 20353464 TI - Phenotypic expression of recurrent disease after liver transplantation. AB - Recurrence of the primary disease has become a major focus for transplant hepatologists both when investigating graft dysfunction and when tailoring immunosuppression to maximize graft survival. However, disease recurrence varies in penetrance, can be predictable or random, and does not always conform to the expected pattern of disease. The cholestatic hepatitis syndromes associated with hepatitis B and C are the most dramatic examples of phenotypic change. Being on immunosuppressive drugs may intensify the progression of infectious and malignant diseases, but this effect is not predictable. A significant minority of patients with each of the autoimmune diseases, counter-intuitively, get recurrent disease despite immunosuppression of a potency that is adequate to prevent rejection of the liver graft. Disease patterns emerge after liver transplantation for cryptogenic cirrhosis that shed light on the cause of the native liver disease, for example, nonalcohol-related fatty liver disease and autoimmune hepatitis. The phenotypic expression of disease recurrence can be modified by specific drugs used for immunosuppression and by HLA-antigen matching profiles. Understanding and modifying the phenotypic expression of recurrent disease after liver transplantation is a fertile area for research and continued refinement of clinical care. PMID- 20353465 TI - Melanoma in solid organ transplant recipients. AB - This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM. PMID- 20353466 TI - Persistent glomerular hematuria in living kidney donors confers a risk of progressive kidney disease in donors after heminephrectomy. AB - Although glomerular hematuria is likely a sign of chronic kidney disease that will develop into overt nephropathy after donation, it remains unclear whether prospective donors with hematuria should be excluded. We reviewed the medical records of 242 donors who donated at our institution from 2001 to 2007 and surveyed the prevalence of hematuria pre- and postdonation. We then investigated the association of hematuria with proteinuria postdonation and trends in glomerular filtration rate. Before donation, 8.3% of 242 donors presented with persistent hematuria, a finding that was significantly associated with dysmorphic hematuria before donation. Most cases of predonation persistent hematuria persisted after donation, and the overall prevalence increased to 15.3%. During a median follow-up period of 2.3 years after donation, 8.3% developed persistent proteinuria, with incidence being significantly higher in donors having persistent hematuria with dysmorphic red blood cells (d-RBC) both before and after donation. Postdonation persistent hematuria with d-RBC was also associated with a progressive decline in renal function. These results indicate that persistent glomerular hematuria is strongly associated with a higher incidence of postdonation progressive kidney disease. Potential donors with persistent glomerular hematuria should be excluded, while those with isolated hematuria need to be evaluated with heightened caution. PMID- 20353467 TI - Vascular stents in the management of portal venous complications in living donor liver transplantation. AB - To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months-59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long-term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow-up was 12 months (range, 3-24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation. PMID- 20353468 TI - Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation. AB - Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 +/- 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P selectin in the skin holds potential to significantly prolong limb allograft survival. PMID- 20353469 TI - The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. AB - Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5. PMID- 20353470 TI - Overview of guidelines for establishing a face transplant program: a work in progress. AB - Since 2005, nine face transplants have been performed in four countries: France, the United States (US), China and Spain. These encouraging short-term outcomes, with the longest survivor approaching 5 years, have led to an increased interest in establishing face transplant programs worldwide. Therefore, the purpose of this article is to facilitate the dissemination of relevant details as per our experience in an effort to assist those medical centers interested in establishing a face transplant program. In this article, we address the logistical challenges involved with face transplantation; including essential program requirements, protocol details, face transplant team assembly, project funding, the organ procurement organization and the coroner. It must be emphasized that face transplantation is still experimental and its therapeutic value remains to be validated. All surgical teams pursuing this endeavor must dedicate an attention to detail and should accept a responsibility to publish their outcomes in a transparent manner in order to contribute to the international field. However, due to its inherent complexity, facial transplantation should only be performed by university-affiliated medical institutions capable of orchestrating a specialized multidisciplinary team with a long-term commitment to its success. PMID- 20353471 TI - Histidine-tryptophan-ketoglutarate for pancreas allograft preservation: the Indiana University experience. AB - Histidine-tryptophan-ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation. A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1 year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (20 patients with GERD, treated with either a proton pump inhibitor or H(2)-receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched, considering only studies that reported a global response for 'heartburn'. RESULTS: A total of 24 studies included 9989 patients with GERD. The pooled odds ratio (OR) for response to active treatment vs. placebo was 3.71 (95% CI: 2.78-4.96). The pooled estimate of the overall placebo response was 18.85% (range 2.94%-47.06%). Patients with erosive oesophagitis had a non-significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; P = 0.246). Placebo response was significantly lower in studies of PPI therapy vs. studies of H(2) RAs (14.51% vs. 24.69%, respectively; P = 0.05). CONCLUSIONS: The placebo response rate in randomized controlled trials for GERD is substantial. A lower placebo response was associated with the testing of PPIs, but not the presence of erosive oesophagitis. PMID- 20353497 TI - Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food? AB - BACKGROUND: Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose. AIM: To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease. METHODS: Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid. RESULTS: B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE. CONCLUSIONS: The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions. PMID- 20353499 TI - Developmental monitoring using caregiver reports in a resource-limited setting: the case of Kilifi, Kenya. AB - AIM: The main aim of the current study was to evaluate the reliability, validity and acceptability of developmental monitoring using caregiver reports among mothers in a rural African setting. METHODS: A structured interview for parents of children aged 24 months and less was developed through both participant consultation and a review of literature. The reliability and validity of the schedule was evaluated through a 10-month monitoring programme of 95 children, aged 2-10 months. The acceptability of the process was evaluated by studying retention rates and by organizing focus group discussions with participating mothers. RESULTS: The structured interview 'Developmental Milestones Checklist' consisted of 66 items covering three broad domains of child functioning: motor, language and personal-social development. The interview yielded scores of developmental achievements that showed high internal consistency and excellent test-retest reliability. The results were sensitive to maturational changes and nutritional deficiencies. In addition, acceptable retention rates of approximately 80% were found. Participating mothers reported that they found the procedures both acceptable and beneficial. CONCLUSION: Developmental monitoring using caregiver report is a viable method to identify and monitor at-risk children in Sub-Saharan Africa. PMID- 20353500 TI - Vincristine, an efficacious alternative for diffuse neonatal haemangiomatosis. AB - Diffuse neonatal haemangiomatosis (DNH) is an uncommon condition characterized by multiple cutaneous and visceral haemangiomas frequently causing severe complications. Corticosteroids constitute the first therapeutic line; however, when they fail, other alternatives are available, provided possible side effects are closely monitored during and after treatment. We present a case of life threatening DNH, non-responsive to corticosteroids, successfully treated with Vincristine with minor side effects. We conclude that Vincristine is a valid alternative in corticosteroid-resistant DNH. PMID- 20353503 TI - An international survey of EEG use in the neonatal intensive care unit. AB - OBJECTIVE: To examine the extent of EEG monitoring in neonatal intensive care units (NICUs), and to survey the level of experience and training of those using it. STUDY DESIGN: A web-based survey, the link to which was circulated via e mail, personal contact, specialist societies and professional groups. Survey data were exported to SPSS for analysis. RESULTS: In total 210 surveys were analysed; 124 from Europe, 54 from the US. Ninety percent of respondents had access to either EEG or aEEG monitoring; 51% had both. EEG was mainly interpreted by neurophysiologists (72%) whereas aEEG was usually interpreted by neonatologists (80%). Only 9% of respondents reported that they felt 'very confident' in their ability to interpret aEEG/EEG with 31% reporting that they were 'not confident'. Half had received no formal training in EEG. CONCLUSION: Both aEEG and conventional EEG were used extensively in the NICUs surveyed for this study. Most of the survey respondents were not confident in their ability to interpret EEGs despite the fact that they used monitoring routinely. There is an urgent need for a structured and appropriately targeted training programme in EEG methodologies and EEG interpretation for neonatal intensive care unit staff. PMID- 20353505 TI - Blood viral load in the management of congenital cytomegalovirus infection. PMID- 20353514 TI - A new universal rat restrainer for ophthalmic research. AB - PURPOSE: Immobilization of rats is required in many psychological and physiological experiments. The aim of the current paper was to invent a universal device allowing for adaptation of rats of a wide age range and to maximize convenience for in vivo exposure to optical radiation under not-anaesthetized conditions. METHODS: Eighty-three 6-week-old and three 18-week-old Sprague-Dawley albino female rats were progressively familiarized daily with the restraining device 5 days prior to exposure to acquire a conditioned response and to reduce stress. After initial habituation, 10 min preceding the ultraviolet radiation (UVR) exposure, the animal was fixed in the rat restrainer. Each unanaesthetized animal was unilaterally exposed to a single dose of 8 kJ/m2 UVR-300 nm for 15 min. Three of the 6-week-old and three of the 18-week-old rats were in vivo exposed to UVR once for 10 consecutive days. RESULTS: All rats acclimatized well to immobilization in the restrainer. Young rats adapted quicker than older rats. The device prevented head movement and body rotation, which allowed for uncomplicated single as well as repeated in vivo exposures to UVR. CONCLUSIONS: The restrainer effectively immobilizes unanaesthetized rats in the age range 6-18 weeks old, making it useful in future projects involving chronic repeated in vivo exposure of the eye to UVR. PMID- 20353515 TI - Autophagy--hot topic in AMD. PMID- 20353516 TI - Functional skin adaptation in infancy - almost complete but not fully competent. AB - Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extrauterine environment. Skin as the outermost organ of mammalians is endowed of multiple functions such as protection, secretion, absorption and thermoregulation. Birth stimulates the epidermal barrier maturation and the skin surface acidification especially in premature infants. In full-term infants the developed stratum corneum accomplishes competent barrier function, in contrast to prematures. Complete barrier maturation in preterm infants is fulfilled by 2-4 weeks of the postnatal life. However, in preterms with 23-25 weeks gestational age this process takes longer. Versatile regulatory mechanisms, namely skin surface acidity, calcium ion gradient and nuclear hormone receptors/ligands are interrelated in the complex postnatal newborn adaptation. The skin of newborns is adjusting quickly to the challenging environmental conditions of the postpartum. However, certain functions, for example, microcirculation, continue to develop even beyond the neonatal period, that is, up to the age of 14-17 weeks. Different environmental factors (for instance, dry and cold climate, diapers and cosmetic care procedures) influence the postnatal development of skin functional parameters such as stratum corneum hydration and the permeability barrier especially in premature infants. The aim of this article is to summarize the current knowledge on skin physiology in newborn and infants with a practical approach and to discuss the possible clinical consequences. This review offers the readership a critical and practical overview of skin physiology in newborns and infants. It emphasizes possible new research fields in neonatal and infantile skin physiology. PMID- 20353518 TI - Young investigator award. PMID- 20353519 TI - Vitamin D deficiency rickets and allegations of non-accidental injury. PMID- 20353520 TI - Does temporary brittle bone disease exist? Not by the evidence offered. PMID- 20353521 TI - Multiple unexplained fractures in infants--the need for clear thinking. PMID- 20353522 TI - A convenient alternative approach to screen for retinopathy of prematurity. PMID- 20353525 TI - A floppy neonate with respiratory failure and burst suppression EEG (case presentation). PMID- 20353526 TI - A girl with a purpuric rash (case presentation). PMID- 20353527 TI - Adhering to your non-adherent patients: the challenge of non-compliance. PMID- 20353528 TI - A boy born with multiple lesions of atrophoderma. AB - AIMS: The Atrophodermas include a large group of disorders appearing as localized or widespread depressed skin areas and characterized by underlying dermal atrophy. The present study aims to report a peculiar form of previously unreported focal dermal atrophy. METHODS: We studied over a period of 5 years a boy who manifested, since birth, multiple hypopigmented cutaneous atrophic lesions of the atrophoderma type in a mosaic distribution over the body and the legs. RESULTS: This boy did no develop other cutaneous or systemic stigmata except for an idiopathic thrombocytopenic purpura (ITP) manifested at age 2 years. Full serum, metabolic and infective analyses; full ophthalmological examination; ultrasound examination of the heart and internal organs; skeletal x rays; brain magnetic resonance imaging; and DNA analysis of the PORCN (Focal Dermal Hypoplasia - FDH) gene in this boy yielded normal results. Pathological analysis of multiple skin specimens from an affected area revealed slightly reduced dermal thickness; hyperpigmentation of the basal layer; homogenized and disarrayed collagen bundles; perivascular chronic infiltrates of lymphocytes and histiocytes; and normal skin appendages. Currently, the child is healthy; he has mildly improved skin status with less-evident skin depression throughout the lesion areas and no further complication has been recorded. The histological and clinical appearance of the skin lesions and the course were against any known disorder in the group of the atrophodermas. CONCLUSIONS: The cutaneous lesions seen in this boy represent a possibly new congenital skin disorder characterized by multiple, benign areas of focal dermal atrophy in a mosaic distribution. PMID- 20353532 TI - A quantitative trait locus responsible for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability. AB - While the molecular mechanisms underlying microsatellite instability (MSI) have been exhaustively investigated, identifying the patterns of MSI distribution within diverse cancer genomes has remained an elusive issue. In the present study, we conducted genome-wide MSI screening in B-cell lymphoblastic lymphomas (B-LBL) which spontaneously develop in the SL/Kh strain of mice. Tumor samples harvested from 16 mice were investigated using a framework map consisting of 150 microsatellite markers spaced at increments of roughly 0.5-3.0 centimorgans, spanning the entirety of mouse chromosomes (mus musculus chromosomes [MMU]) 3-6. MMU3 contains a quantitative trait locus (QTL), Bomb1 (bone marrow pre-B1), known to induce an aberrant expansion of pre-B cells in bone marrow prior to the onset of B-LBL in SL/Kh mice. The remaining chromosomes were selected on the basis of those most closely resembling MMU3 in terms of total estimated length (maximum variance 10 Mb). MSI was confirmed at 2 or =70 years. PMID- 20353540 TI - Preoperative assessment for major urological surgery: where are we now? PMID- 20353542 TI - Outpatient novel 'out-leaf' (ONOL) procedure for idiopathic hydrocele. PMID- 20353543 TI - Tracing the evolution of tissue identity with microRNAs. AB - Comparison of microRNA expression identified tissues present in the last common ancestor of Bilaterians and put evolution of microRNAs in the context of tissue evolution. PMID- 20353544 TI - Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders. AB - Diagnosing neurodegenerative diseases, monitoring their progression and assessing responses to treatments will all be aided by the identification of molecular markers of different stages of pathology. Protein biomarkers for HIV-associated neurocognitive disorders that have been discovered using proteomics include complement C3, soluble superoxide dismutase and a prostaglandin synthase. Metabolomics has not yet been widely used for biomarker discovery, but early work shows that it has great potential. PMID- 20353546 TI - No stone unturned. PMID- 20353545 TI - The yin and yang of chromatin spatial organization. AB - Spatial organization of the genome is non-random. Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization. PMID- 20353547 TI - Dividing intensive care specialists according to their backgrounds is not useful to improve quality in intensive care. PMID- 20353548 TI - The mathematics of sexual attraction. AB - Pollen tubes follow attractants secreted by the ovules. In a recent paper in BMC Plant Biology, Stewman and colleagues have quantified the parameters of this attraction and used them to calibrate a mathematical model that reproduces the process and enables predictions on the nature of the female attractant and the mechanisms of the male response. PMID- 20353549 TI - Cardiac arrest - has the time of MRI come? AB - Three recent articles have shown the potential use of magnetic resonance imaging for the evaluation of comatose survivors of cardiac arrest. While this technique appears promising, significant additional work is required before it can be routinely used in a clinical setting. PMID- 20353550 TI - What the hyena's laugh tells: sex, age, dominance and individual signature in the giggling call of Crocuta crocuta. AB - BACKGROUND: Among mammals living in social groups, individuals form communication networks where they signal their identity and social status, facilitating social interaction. In spite of its importance for understanding of mammalian societies, the coding of individual-related information in the vocal signals of non-primate mammals has been relatively neglected. The present study focuses on the spotted hyena Crocuta crocuta, a social carnivore known for its complex female-dominated society. We investigate if and how the well-known hyena's laugh, also known as the giggle call, encodes information about the emitter. RESULTS: By analyzing acoustic structure in both temporal and frequency domains, we show that the hyena's laugh can encode information about age, individual identity and dominant/subordinate status, providing cues to receivers that could enable assessment of the social position of an emitting individual. CONCLUSIONS: The range of messages encoded in the hyena's laugh is likely to play a role during social interactions. This call, together with other vocalizations and other sensory channels, should ensure an array of communication signals that support the complex social system of the spotted hyena. Experimental studies are now needed to decipher precisely the communication network of this species. PMID- 20353551 TI - Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial. AB - INTRODUCTION: Although exercise is therapeutic for adults with fibromyalgia (FM), its symptoms often create obstacles that discourage exercise. We evaluated the effects of accumulating at least 30 minutes of self-selected lifestyle physical activity (LPA) on perceived physical function, pain, fatigue, body mass index, depression, tenderness, and the six-minute walk test in adults with FM. METHODS: Eighty-four minimally active adults with FM were randomized to either LPA or a FM education control (FME) group. LPA participants worked toward accumulating 30 minutes of self-selected moderate-intensity LPA, five to seven days per week, while the FME participants received information and support. RESULTS: Seventy three of the 84 participants (87%) completed the 12-week trial. The LPA group increased their average daily steps by 54%. Compared to FME, the LPA group reported significantly less perceived functional deficits (P = .032) and less pain (P = .006). There were no differences between the groups on the six-minute walk test (P = .067), fatigue, depression, body mass index, or tenderness. CONCLUSIONS: Accumulating 30 minutes of LPA throughout the day produces clinically relevant changes in perceived physical function and pain in previously minimally active adults with FM. TRIAL REGISTRATION: clinicaltrials.gov NCT00383084. PMID- 20353552 TI - Elderly patients undergoing mechanical ventilation in and out of intensive care units: a comparative, prospective study of 579 ventilations. AB - INTRODUCTION: Many mechanically ventilated elderly patients in Israel are treated outside of intensive care units (ICUs). The decision as to whether these patients should be treated in ICUs is reached without clear guidelines. We therefore conducted a study with the aim of identifying triage criteria and factors associated with in-hospital mortality in this population. METHODS: All mechanically invasive ventilated elderly (65+) medical patients in the hospital were included in a prospective, non-interventional, observational study. RESULTS: Of the 579 ventilations, 283 (48.9%) were done in ICUs compared with 296 (51.1%) in non-ICU wards. The percentage of ICU ventilations in the 65 to 74, 75 to 84, and 85+ age groups was 62%, 45%, and 23%, respectively. The decision to ventilate in ICUs was significantly and independently influenced by age (Odds Ratio (OR) = 0.945, P < 0.001), and pre-hospitalization functional status by functional independence measure (FIM) scale (OR = 1.054, P < 0.001). In-hospital mortality was 53.0% in ICUs compared with 68.2% in non-ICU wards (P < 0.001), but the rate was not independently and significantly affected by hospitalization in ICUs. CONCLUSIONS: In Israel, most elderly patients are ventilated outside ICUs and the percentage of ICU ventilations decreases as age increases. In our study groups, the lower mortality among elderly patients ventilated in ICUs is related to patient characteristics and not to their treatment in ICUs per se. Although the milieu in which this study was conducted is uncommon today in the western world, its findings point to possible means of managing future situations in which the demand for mechanical ventilation of elderly patients exceeds the supply of intensive care beds. Moreover, the findings of this study can contribute to the search for ways to reduce costs without having a negative effect on outcome in ventilated elderly patients. PMID- 20353553 TI - Identification of NAD interacting residues in proteins. AB - BACKGROUND: Small molecular cofactors or ligands play a crucial role in the proper functioning of cells. Accurate annotation of their target proteins and binding sites is required for the complete understanding of reaction mechanisms. Nicotinamide adenine dinucleotide (NAD+ or NAD) is one of the most commonly used organic cofactors in living cells, which plays a critical role in cellular metabolism, storage and regulatory processes. In the past, several NAD binding proteins (NADBP) have been reported in the literature, which are responsible for a wide-range of activities in the cell. Attempts have been made to derive a rule for the binding of NAD+ to its target proteins. However, so far an efficient model could not be derived due to the time consuming process of structure determination, and limitations of similarity based approaches. Thus a sequence and non-similarity based method is needed to characterize the NAD binding sites to help in the annotation. In this study attempts have been made to predict NAD binding proteins and their interacting residues (NIRs) from amino acid sequence using bioinformatics tools. RESULTS: We extracted 1556 proteins chains from 555 NAD binding proteins whose structure is available in Protein Data Bank. Then we removed all redundant protein chains and finally obtained 195 non-redundant NAD binding protein chains, where no two chains have more than 40% sequence identity. In this study all models were developed and evaluated using five-fold cross validation technique on the above dataset of 195 NAD binding proteins. While certain type of residues are preferred (e.g. Gly, Tyr, Thr, His) in NAD interaction, residues like Ala, Glu, Leu, Lys are not preferred. A support vector machine (SVM) based method has been developed using various window lengths of amino acid sequence for predicting NAD interacting residues and obtained maximum Matthew's correlation coefficient (MCC) 0.47 with accuracy 74.13% at window length 17. We also developed a SVM based method using evolutionary information in the form of position specific scoring matrix (PSSM) and obtained maximum MCC 0.75 with accuracy 87.25%. CONCLUSION: For the first time a sequence-based method has been developed for the prediction of NAD binding proteins and their interacting residues, in the absence of any prior structural information. The present model will aid in the understanding of NAD+ dependent mechanisms of action in the cell. To provide service to the scientific community, we have developed a user-friendly web server, which is available from URL http://www.imtech.res.in/raghava/nadbinder/. PMID- 20353554 TI - Are the elderly more vulnerable to psychological impact of natural disaster? A population-based survey of adult survivors of the 2008 Sichuan earthquake. AB - BACKGROUND: The association between ages and psychological impact of natural disasters has not been well characterized. A population-based study was conducted 15 months after the 2008 Sichuan earthquake to assess whether elderly survivors were more likely to develop posttraumatic stress disorder (PTSD) and general psychiatric morbidity. METHODS: A population-based survey of 327 survivors (152 elders, 175 younger adults) was conducted in severely affected areas by the earthquake, using a multi-stage systematic sampling design. RESULTS: Compared with the younger adult survivors, the elderly were more likely to have symptoms of PTSD (22.5% vs. 8.0%, p = 0.001) and general psychiatric morbidity (42.0% vs. 25.4%, p = 0.003). Risk factors, such as being elderly, having been in serious danger, having lost family members, and having felt guilt concerning one's death or injury were significantly associated with developing PTSD; being elderly, having family members or friends seriously injured, and having felt guilt concerning one's death or injury were significantly associated with developing general psychiatric morbidity. Utilization of mental health services is strongly associated with the decreased risk for developing both of the symptoms. CONCLUSION: Compared with the younger adults, the elderly survivors were more likely to develop PTSD and general psychiatric morbidity. More mental health services should be distributed to the elderly and groups at particular risk, to ensure their smooth mental health reconstruction after the earthquake. PMID- 20353555 TI - To signal or not to signal? Chemical communication by urine-borne signals mirrors sexual conflict in crayfish. AB - BACKGROUND: Sexual selection theory predicts that females, being the limiting sex, invest less in courtship signals than males. However, when chemical signals are involved it is often the female that initiates mating by producing stimuli that inform about sex and/or receptivity. This apparent contradiction has been discussed in the literature as 'the female pheromone fallacy'. Because the release of chemical stimuli may not have evolved to elicit the male's courtship response, whether these female stimuli represent signals remains an open question. Using techniques to visualise and block release of urine, we studied the role of urine signals during fighting and mating interactions of crayfish (Pacifastacus leniusculus). Test individuals were blindfolded to exclude visual disturbance from dye release and artificial urine introduction. RESULTS: Staged female-male pairings during the reproductive season often resulted in male mating attempts. Blocking female urine release in such pairings prevented any male courtship behaviour. Artificial introduction of female urine re-established male mating attempts. Urine visualisation showed that female urine release coincides with aggressive behaviours but not with female submissive behaviour in reproductive interactions as well as in intersexual and intrasexual fights. In reproductive interactions, females predominately released urine during precopulatory aggression; males subsequently released significantly less urine during mating than in fights. CONCLUSIONS: Urine-blocking experiments demonstrate that female urine contains sex-specific components that elicit male mating behaviour. The coincidence of chemical signalling and aggressive behaviour in both females and males suggests that urine release has evolved as an aggressive signal in both sexes of crayfish. By limiting urine release to aggressive behaviours in reproductive interactions females challenge their potential mating partners at the same time as they trigger a sexual response. These double messages should favour stronger males that are able to overcome the resistance of the female. We conclude that the difference between the sexes in disclosing urine borne information reflects their conflicting interests in reproduction. Males discontinue aggressive urine signalling in order to increase their chances of mating. Females resume urine signalling in connection with aggressive behaviour, potentially repelling low quality or sexually inactive males while favouring reproduction with high quality males. PMID- 20353556 TI - Molecular evidence for a diverse green algal community growing in the hair of sloths and a specific association with Trichophilus welckeri (Chlorophyta, Ulvophyceae). AB - BACKGROUND: Sloths are slow-moving arboreal mammals inhabiting tropical rainforests in Central and South America. The six living species of sloths are occasionally reported to display a greenish discoloration of their pelage. Trichophilus welckeri, a green algal species first described more than a century ago, is widely believed to discolor the animals fur and provide the sloth with effective camouflage. However, this phenomenon has not been explored in any detail and there is little evidence to substantiate this widely held opinion. RESULTS: Here we investigate the genetic diversity of the eukaryotic community present in fur of all six extant species of sloth. Analysis of 71 sloth hair samples yielding 426 partial 18S rRNA gene sequences demonstrates a diverse eukaryotic microbial assemblage. Phylogenetic analysis reveals that sloth fur hosts a number of green algal species and suggests that acquisition of these organisms from the surrounding rainforest plays an important role in the discoloration of sloth fur. However, an alga corresponding to the morphological description of Trichophilus welckeri was found to be frequent and abundant on sloth fur. Phylogenetic analysis demonstrated the retention of this alga on the fur of sloths independent of geographic location. CONCLUSIONS: These results demonstrate a unique diverse microbial eukaryotic community in the fur of sloths from Central and South America. Our analysis streghtens the case for symbiosis between sloths and Trichophilus welckeri. PMID- 20353557 TI - The epidemiology of hospitalized influenza in children, a two year population based study in the People's Republic of China. AB - BACKGROUND: The epidemiology and disease burden of annual influenza in children in mainland People's Republic of China have not been reported in detail. To understand the incidence and epidemiology of laboratory-proven influenza hospitalization in children in China, a review of available laboratory and hospital admission data was undertaken. METHODS: We conducted a retrospective population-based study in Suzhou and the surrounding area of Jiangsu province, China for hospitalized cases of respiratory illness at Suzhou Children's Hospital. Cases of pneumonia or respiratory illness were identified from hospital computer data bases. Routine virological testing by fluorescent monoclonal antibody assay of all hospitalized children identified influenza and other viruses. We calculated incidence rates using census population denominators. RESULTS: Of 7,789 specimens obtained during 2007 and 2008, 85 were positive for influenza A and 25 for influenza B. There were 282 specimens with parainfluenza virus and 1392 with RSV. Influenza occurred throughout the year, with peaks in the winter, and in August/September. Overall estimated annual incidence of laboratory-proven influenza hospitalization was 23-27/100,000 children 0-4 years old, and 60/100,000 in infants 0-6 months, with an average hospitalization of 9 days. CONCLUSIONS: Influenza disease in young children in this part of China is a relatively common cause of hospitalization, and occurs throughout the year. The use of influenza vaccine in Chinese children has the potential to reduce the effect of influenza in the children, as well as in their communities. Studies are needed to further assess the burden of influenza, and to develop and refine effective strategies of immunization of young children in China. PMID- 20353558 TI - Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation. AB - BACKGROUND: Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. RESULTS: Hepato-transcriptome analysis of mercury exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. CONCLUSION: Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling pathway, gluconeogenesis, and adipogenesis, leading to mitochondrial dysfunction, endocrine disruption and metabolic disorders. This study provides important mechanistic insights into mercury-induced liver toxicity in a whole animal physiology context, which will help in understanding the syndromes caused by mercury poisoning. The molecular conservation of mercury-induced hepatotoxicity between zebrafish and human cell line reveals the feasibility of using zebrafish to model molecular toxicity in human for toxicant risk assessments. PMID- 20353559 TI - Calcium deposition in osteoarthritic meniscus and meniscal cell culture. AB - INTRODUCTION: Calcium crystals exist in the knee joint fluid of up to 65% of osteoarthritis (OA) patients and the presence of these calcium crystals correlates with the radiographic evidence of hyaline cartilaginous degeneration. This study sought to examine calcium deposition in OA meniscus and to investigate OA meniscal cell-mediated calcium deposition. The hypothesis was that OA meniscal cells may play a role in pathological meniscal calcification. METHODS: Studies were approved by our human subjects Institutional Review Board. Menisci were collected during joint replacement surgeries for OA patients and during limb amputation surgeries for osteosarcoma patients. Calcium deposits in menisci were examined by alizarin red staining. Expression of genes involved in biomineralization in OA meniscal cells was examined by microarray and real-time RT-PCR. Cell-mediated calcium deposition in monolayer culture of meniscal cells was examined using an ATP-induced (45)calcium deposition assay. RESULTS: Calcium depositions were detected in OA menisci but not in normal menisci. The expression of several genes involved in biomineralization including ENPP1 and ANKH was upregulated in OA meniscal cells. Consistently, ATP-induced calcium deposition in the monolayer culture of OA meniscal cells was much higher than that in the monolayer culture of control meniscal cells. CONCLUSIONS: Calcium deposition is common in OA menisci. OA meniscal cells calcify more readily than normal meniscal cells. Pathological meniscal calcification, which may alter the biomechanical properties of the knee meniscus, is potentially an important contributory factor to OA. PMID- 20353560 TI - Expression and regulation of HIF-1alpha in macrophages under inflammatory conditions; significant reduction of VEGF by CaMKII inhibitor. AB - BACKGROUND: Macrophages expressing the pro-angiogenic transcription factor hypoxia-inducible factor (HIF)-1alpha have been demonstrated in rheumatoid arthritis (RA) in the synovial tissue. Aim of the present study was to investigate intracellular signal transduction regulation of pro-inflammatory HIF 1 alpha expression in macrophages to identify possible new intervention strategies. We investigated the effects of CaMKII-inhibitors amongst other kinase inhibitors, on HIF-1 alpha expression and downstream production of pro-angiogenic factors in macrophages. METHODS: Differentiated THP-1 cells and synovial fluid (SF) macrophages were stimulated with 1 microg/ml LPS with or without pretreatment with specific inhibitors of the ERK pathway (PD98059), the PI3K pathway (LY294002), and the CaMKII pathway (KN93 and SMP-114). mRNA and protein expression of HIF-1 alpha, VEGF, MMP-9, and IL-8 was measured in cell lysates and cell supernatants. RESULTS: HIF-1 alpha protein expression in LPS-stimulated THP 1 macrophages could be blocked by ERK- and PI3K-inhibitors, but also by the CaMKII inhibitor KN93. THP-1 and SF macrophages produced high levels of VEGF, IL 8, and MMP-9, and VEGF protein production was significantly inhibited by PI3K inhibitor, and by both CaMKII inhibitors. LPS stimulation in an hypoxic environment did not change VEGF levels, suggesting that LPS induced VEGF production in macrophages is more important than the hypoxic induction. CONCLUSIONS: Expression of HIF-1 alpha and downstream effects in macrophages are regulated by ERK-, PI3K, but also by CaMKII pathways. Inhibition of HIF-1alpha protein expression and significant inhibition of VEGF production in macrophages was found using CaMKII inhibitors. This is an unknown but very interesting effect of the CaMKII inhibitor SMP-114, which has been in clinical trial as DMARD for the treatment of RA. This effect may contribute to the anti-arthritic effects of SMP-114. PMID- 20353561 TI - Supervision of community peer counsellors for infant feeding in South Africa: an exploratory qualitative study. AB - BACKGROUND: Recent years have seen a re-emergence of community health worker (CHW) interventions, especially in relation to HIV care, and in increasing coverage of child health interventions. Such programmes can be particularly appealing in the face of human resource shortages and fragmented health systems. However, do we know enough about how these interventions function in order to support the investment? While research based on strong quantitative study designs such as randomised controlled trials increasingly document their impact, there has been less empirical analysis of the internal mechanisms through which CHW interventions succeed or fail. Qualitative process evaluations can help fill this gap. METHODS: This qualitative paper reports on the experience of three CHW supervisors who were responsible for supporting infant feeding peer counsellors. The intervention took place in three diverse settings in South Africa. Each setting employed one CHW supervisor, each of whom was individually interviewed for this study. The study forms part of the process evaluation of a large-scale randomized controlled trial of infant feeding peer counselling support. RESULTS: Our findings highlight the complexities of supervising and supporting CHWs. In order to facilitate effective infant feeding peer counselling, supervisors in this study had to move beyond mere technical management of the intervention to broader people management. While their capacity to achieve this was based on their own prior experience, it was enhanced through being supported themselves. In turn, resource limitations and concerns over safety and being in a rural setting were raised as some of the challenges to supervision. Adding to the complexity was the issue of HIV. Supervisors not only had to support CHWs in their attempts to offer peer counselling to mothers who were potentially HIV positive, but they also had to deal with supporting HIV-positive peer counsellors. CONCLUSIONS: This study highlights the need to pay attention to the experiences of supervisors so as to better understand the components of supervision in the field. Such understanding can enhance future policy making, planning and implementation of peer community health worker programmes. PMID- 20353562 TI - The percentage of CD133+ cells in human colorectal cancer cell lines is influenced by Mycoplasma hyorhinis infection. AB - BACKGROUND: Mollicutes contamination is recognized to be a critical issue for the cultivation of continuous cell lines. In this work we characterized the effect of Mycoplasma hyorhinis contamination on CD133 expression in human colon cancer cell lines. METHODS: MycoAlert and mycoplasma agar culture were used to detect mycoplasma contamination on GEO, SW480 and HT-29 cell lines. Restriction fragment length polymorphism assay was used to determine mycoplasma species. All cellular models were decontaminated by the use of a specific antibiotic panel (Enrofloxacin, Ciprofloxacin, BM Cyclin 1 and 2, Mycoplasma Removal Agent and MycoZap). The percentage of CD133 positive cells was analyzed by flow cytometry on GEO, SW480 and HT-29 cell lines, before and after Mycoplasma hyorhinis eradication. RESULTS: Mycoplasma hyorhinis infected colon cancer cell lines showed an increased percentage of CD133+ cells as compared to the same cell lines rendered mycoplasma-free by effective exposure to antibiotic treatment. The percentage of CD133 positive cells increased again when mycoplasma negative cells were re-infected by Mycoplasma hyorhinis. CONCLUSIONS: Mycoplasma hyorhinis infection has an important role on the quality of cultured human colon cancer cell lines giving a false positive increase of cancer stem cells fraction characterized by CD133 expression. Possible explanations are (i) the direct involvement of Mycoplasma on CD133 expression or (ii) the selective pressure on a subpopulation of cells characterized by constitutive CD133 expression.In keeping with United Kingdom Coordinating Committee on Cancer Research (UKCCCR) guidelines, the present data indicate the mandatory prerequisite, for investigators involved in human colon cancer research area, of employing mycoplasma-free cell lines in order to avoid the production of non-reproducible or even false data. PMID- 20353563 TI - The epidemiology of bacterial vaginosis in relation to sexual behaviour. AB - BACKGROUND: Bacterial vaginosis (BV) has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs). It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic micro-organisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour. DISCUSSION: G. vaginalis carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. G. vaginalis carriage is enhanced by penetrative sexual contact but also by non-penetrative digito-genital contact and oral sex, again indicating that sex per se, but not necessarily coital transmission is involved. Several observations also point at female-to-male rather than at male-to-female transmission of G. vaginalis, presumably explaining the high concordance rates of G. vaginalis carriage among couples. Male antibiotic treatment has not been found to protect against BV, condom use is slightly protective, whereas male circumcision might protect against BV. BV is also common among women-who-have-sex-with-women and this relates at least in part to non-coital sexual behaviours. Though male-to-female transmission cannot be ruled out, overall there is little evidence that BV acts as an STD. Rather, we suggest BV may be considered a sexually enhanced disease (SED), with frequency of intercourse being a critical factor. This may relate to two distinct pathogenetic mechanisms: (1) in case of unprotected intercourse alkalinisation of the vaginal niche enhances a shift from lactobacilli-dominated microflora to a BV-like type of microflora and (2) in case of unprotected and protected intercourse mechanical transfer of perineal enteric bacteria is enhanced by coitus. A similar mechanism of mechanical transfer may explain the consistent link between non-coital sexual acts and BV. Similar observations supporting the SED pathogenetic model have been made for vaginal candidiasis and for urinary tract infection. SUMMARY: Though male-to-female transmission cannot be ruled out, overall there is incomplete evidence that BV acts as an STI. We believe however that BV may be considered a sexually enhanced disease, with frequency of intercourse being a critical factor. PMID- 20353565 TI - Allelic variants of IL1R1 gene associate with severe hand osteoarthritis. AB - BACKGROUND: In search for genes predisposing to osteoarthritis (OA), several genome wide scans have provided evidence for linkage on 2q. In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families. METHODS: We genotyped 32 single nucleotide polymorphisms (SNPs) in this 470 kb region comprising six genes belonging to the interleukin 1 superfamily and monitored for association with individual SNPs and SNP haplotypes among severe familial hand OA cases (material extended from our previous linkage study; n = 134), unrelated end-stage bilateral primary knee OA cases (n = 113), and population based controls (n = 436). RESULTS: Four SNPs in the IL1R1 gene, mapping to a 125 kb LD block, provided evidence for association with hand OA in family-based and case-control analysis, the strongest association being with SNP rs2287047 (p-value = 0.0009). CONCLUSIONS: This study demonstrates an association between severe hand OA and IL1R1 gene. This gene represents a highly relevant biological candidate since it encodes protein that is a known modulator of inflammatory processes associated with joint destruction and resides within a locus providing consistent evidence for linkage to hand OA. As the observed association did not fully explain the linkage obtained in the previous study, it is plausible that also other variants in this genome region predispose to hand OA. PMID- 20353564 TI - Structural and functional studies of STAT1 from Atlantic salmon (Salmo salar). AB - BACKGROUND: Type I and type II interferons (IFNs) exert their effects mainly through the JAK/STAT pathway, which is presently best described in mammals. STAT1 is involved in signaling pathways induced by both types of IFNs. It has a domain like structure including an amino-terminus that stabilizes interaction between STAT dimers in a promoter-binding situation, a coiled coil domain facilitating interactions to other proteins, a central DNA-binding domain, a SH2 domain responsible for dimerization of phosphorylated STATs and conserved phosphorylation sites within the carboxy terminus. The latter is also the transcriptional activation domain. RESULTS: A salmon (Salmo salar) STAT1 homologue, named ssSTAT1a, has been identified and was shown to be ubiquitously expressed in various cells and tissues. The ssSTAT1a had a domain-like structure with functional motifs that are similar to higher vertebrates. Endogenous STAT1 was shown to be phosphorylated at tyrosine residues both in salmon leukocytes and in TO cells treated with recombinant type I and type II IFNs. Also ectopically expressed ssSTAT1 was phosphorylated in salmon cells upon in vitro stimulation by the IFNs, confirming that the cloned gene was recognized by upstream tyrosine kinases. Treatment with IFNs led to nuclear translocation of STAT1 within one hour. The ability of salmon STAT1 to dimerize was also shown. CONCLUSIONS: The structural and functional properties of salmon STAT1 resemble the properties of mammalian STAT1. PMID- 20353566 TI - Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1). AB - BACKGROUND: After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. METHODS: We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. RESULTS: Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. CONCLUSIONS: Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening. PMID- 20353567 TI - Cost implications of delays to tuberculosis diagnosis among pulmonary tuberculosis patients in Ethiopia. AB - BACKGROUND: Delays seeking care worsen the burden of tuberculosis and cost of care for patients, families and the public health system. This study investigates costs of tuberculosis diagnosis incurred by patients, escorts and the public health system in 10 districts of Ethiopia. METHODS: New pulmonary tuberculosis patients > or = 15 years old were interviewed regarding their health care seeking behaviour at the time of diagnosis. Using a structured questionnaire patients were interviewed about the duration of delay at alternative care providers and the public health system prior to diagnosis. Costs incurred by patients, escorts and the public health system were quantified through patient interview and review of medical records. RESULTS: Interviews were held with 537 (58%) smear positive patients and 387 (42%) smear negative pulmonary patients. Of these, 413 (45%) were female; 451 (49%) were rural residents; and the median age was 34 years. The mean (median) days elapsed for consultation at alternative care providers and public health facilities prior to tuberculosis diagnosis was 5 days (0 days) and 3 (3 days) respectively. The total median cost incurred from first consultation to diagnosis was $27 per patient (mean = $59). The median costs per patient incurred by patient, escort and the public health system were $16 (mean = $29), $3 (mean = $23) and $3 (mean = $7) respectively. The total cost per patient diagnosed was higher for women, rural residents; those who received government food for work support, patients with smear negative pulmonary tuberculosis and patients who were not screened for TB in at least one district diagnostic centers. CONCLUSIONS: The costs of tuberculosis diagnosis incurred by patients and escorts represent a significant portion of their monthly income. The costs arising from time lost in seeking care comprised a major portion of the total cost of diagnosis, and may worsen the economic position of patients and their families. Getting treatment from alternative sources and low index of suspicion public health providers were key problems contributing to increased cost of tuberculosis diagnosis. Thus, the institution of effective systems of referral, ensuring screening of suspects across the district public health system and the involvement of alternative care providers in district tuberculosis control can reduce delays and the financial burden to patients and escorts. PMID- 20353568 TI - Behavioural intentions in response to an influenza pandemic. AB - BACKGROUND: Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. METHODS: A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. RESULTS: Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. CONCLUSIONS: Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react. PMID- 20353569 TI - Clinical deterioration during antituberculosis treatment in Africa: incidence, causes and risk factors. AB - BACKGROUND: HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration. METHODS: Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment. RESULTS: Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/microL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/microL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/microL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/microL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/microL. CONCLUSIONS: In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/microL will likely reduce the high burden of clinical deterioration. PMID- 20353570 TI - Factors associated with early menarche: results from the French Health Behaviour in School-aged Children (HBSC) study. AB - BACKGROUND: Puberty is a transition period making physiological development a challenge adolescents have to face. Early pubertal development could be associated with higher risks of poor health. Our objective was to examine risk behaviours, physical and psychological determinants associated with early menarche (<11 years). METHODS: Early menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire from a nationally representative sample of 1072 15 years old girls in school classrooms. Family environment, school experience, physical and psychological factors, risk behaviours (substance use and sexual initiation) were recorded. Logistic regression models were applied (analysing for crude and adjusted relationships between early menarche and risk behaviours controlled for family context). RESULTS: Median age at menarche was 13.0 years; 57 girls (5.3%) were early matured. Controlled for familial environment, early menarche was associated with having had more than two life-drunkenness episodes (adjusted OR = 2.5 [1.3-4.6]), early sexual initiation (adjusted OR = 2.8 [1.3-6.0]) and overweight (adjusted OR = 7.3 [3.6-14.9]). CONCLUSION: Early-maturing girls may affiliate with older adolescents, hence engage in risk behaviours linked to their appearance rather than their maturity level. Factors associated with early menarche highlight the need to focus attention on early-matured girls to prevent further health problems linked to risk behaviours. PMID- 20353572 TI - A framework for evaluating the impact of the United Nations fellowship programmes. AB - The United Nations (UN) System's agencies have been criticized for not adequately assessing the impact of their training and fellowship programmes. Critics point out that beyond documentation of the number of fellows that underwent training, and their immediate reaction to the experience, it is necessary to ascertain that fellows are using what they have learned, and most importantly that their institution and country are benefiting from the significant investments made in the fellowship programmes.This paper presents an evaluation framework that was adopted by the 17th Meeting of the UN System Senior Fellowship Officers convened in London in 2008 in response to this challenge. It is arranged in three sections. First, the assumptions and constraints concerning impact evaluation of training are presented. Second, a framework for evaluating the impact of training in the context of UN System programmes is proposed. Third, necessary conditions and supportive measures to enable implementation of the impact evaluation framework are identified.The critical message emerging from this review is the importance of constructing a 'performance story' based on key milestones associated with the design and implementation of fellowship programmes as a way of assessing the contribution of different components of the fellowship programmes to institutional outcomes. PMID- 20353573 TI - Carcinoma ex pleomorphic adenoma of soft palate with cavernous sinus invasion. AB - BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy and rare in minor salivary gland. A soft palate CXPA initially presenting as direct cavernous sinus (CS) invasion is very rare. CASE PRESENTATION: A 60-year-old male had a 3-month history of a small soft palatal mass with progressing left cheek numbness, proptosis, and disturbed vision. Biopsy of soft palatal tumor showed pleomorphic adenoma. Magnetic resonance imaging showed a tumor involving left maxilla, and extended from pterygopalatine fossa, inferior orbital fissure to CS. Excision of tumor revealed CXPA. Adjuvant concomitant chemo-radiation therapy (CCRT) was given. The tumor recurred 5 months later in left CS which was re-treated with CCRT. The disease status was stable at 2 years after the diagnosis of CXPA. CONCLUSION: We present this case to emphasize that patients with symptoms such as facial numbness, proptosis and disturbed vision should be carefully investigated for lesions invading CS by perineural spread. PMID- 20353574 TI - Antibodies to actin in autoimmune haemolytic anaemia. AB - BACKGROUND: In autoimmune haemolytic anaemia (AIHA), autoreactive antibodies directed against red blood cells are up-regulated, leading to erythrocyte death. Mycoplasma suis infections in pigs induce AIHA of both the warm and cold types. The aim of this study was to identify the target autoantigens of warm autoreactive IgG antibodies. Sera from experimentally M. suis-infected pigs were screened for autoreactivity. RESULTS: Actin-reactive antibodies were found in the sera of 95% of all animals tested. The reactivity was species-specific, i.e. reactivity with porcine actin was significantly higher than with rabbit actin. Sera of animals previously immunised with the M. suis adhesion protein MSG1 showed reactivity with actin prior to infection with M. suis indicating that molecular mimicry is involved in the specific autoreactive mechanism. A potentially cross-reactive epitope was detected. CONCLUSIONS: This is the first report of autoreactive anti-actin antibodies involved in the pathogenesis of autoimmune haemolytic anaemia. PMID- 20353571 TI - An insight into the sialome of Glossina morsitans morsitans. AB - BACKGROUND: Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's anti-bleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family. Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae. RESULTS: As part of the effort to sequence the genome of Glossina morsitans morsitans, several organ specific, high quality normalized cDNA libraries have been constructed, from which over 20,000 ESTs from an adult salivary gland library were sequenced. These ESTs have been assembled using previously described ESTs from the fat body and midgut libraries of the same fly, thus totaling 62,251 ESTs, which have been assembled into 16,743 clusters (8,506 of which had one or more EST from the salivary gland library). Coding sequences were obtained for 2,509 novel proteins, 1,792 of which had at least one EST expressed in the salivary glands. Despite library normalization, 59 transcripts were overrepresented in the salivary library indicating high levels of expression. This work presents a detailed analysis of the salivary protein families identified. Protein expression was confirmed by 2D gel electrophoresis, enzymatic digestion and mass spectrometry. Concurrently, an initial attempt to determine the immunogenic properties of selected salivary proteins was undertaken. CONCLUSIONS: The sialome of G. m. morsitans contains over 250 proteins that are possibly associated with blood feeding. This set includes alleles of previously described gene products, reveals new evidence that several salivary proteins are multigenic and identifies at least seven new polypeptide families unique to Glossina. Most of these proteins have no known function and thus, provide a discovery platform for the identification of novel pharmacologically active compounds, innovative vector-based vaccine targets, and immunological markers of vector exposure. PMID- 20353575 TI - Temporal context and conditional associative learning. AB - BACKGROUND: We investigated how temporal context affects the learning of arbitrary visuo-motor associations. Human observers viewed highly distinguishable, fractal objects and learned to choose for each object the one motor response (of four) that was rewarded. Some objects were consistently preceded by specific other objects, while other objects lacked this task irrelevant but predictive context. RESULTS: The results of five experiments showed that predictive context consistently and significantly accelerated associative learning. A simple model of reinforcement learning, in which three successive objects informed response selection, reproduced our behavioral results. CONCLUSIONS: Our results imply that not just the representation of a current event, but also the representations of past events, are reinforced during conditional associative learning. In addition, these findings are broadly consistent with the prediction of attractor network models of associative learning and their prophecy of a persistent representation of past objects. PMID- 20353576 TI - ProbFAST: Probabilistic functional analysis system tool. AB - BACKGROUND: The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis. RESULTS: We proposed a web platform named ProbFAST for MDE analysis which uses Bayesian inference to identify key genes that are intuitively prioritized by means of probabilities. A simulated study revealed that our method gives a better performance when compared to other approaches and when applied to public expression data, we demonstrated its flexibility to obtain relevant genes biologically associated with normal and abnormal biological processes. CONCLUSIONS: ProbFAST is a free accessible web-based application that enables MDE analysis on a global scale. It offers an efficient methodological approach for MDE analysis of a set of genes that are turned on and off related to functional information during the evolution of a tumor or tissue differentiation. ProbFAST server can be accessed at http://gdm.fmrp.usp.br/probfast. PMID- 20353577 TI - Validity and reliability of a multiple-group measurement scale for interprofessional collaboration. AB - BACKGROUND: Many measurement scales for interprofessional collaboration are developed for one health professional group, typically nurses. Evaluating interprofessional collaborative relationships can benefit from employing a measurement scale suitable for multiple health provider groups, including physicians and other health professionals. To this end, the paper begins development of a new interprofessional collaboration measurement scale designed for use with nurses, physicians, and other professionals practicing in contemporary acute care settings. The paper investigates validity and reliability of data from nurses evaluating interprofessional collaboration of physicians and shows initial results for other rater/target combinations. METHODS: Items from a published scale originally designed for nurses were adapted to a round robin proxy report format appropriate for multiple health provider groups. Registered nurses, physicians, and allied health professionals practicing in inpatient wards/services of 15 community and academic hospitals in Toronto, Canada completed the adapted scale. Exploratory and confirmatory factor analysis of responses to the adapted scale examined dimensionality, construct and concurrent validity, and reliability of nurses' response data. Correlations between the adapted scale, the nurse-physician relations subscale of the Nursing Work Index, and the Attitudes Toward Health Care Teams Scale were calculated. Differences of mean scores on the Nursing Work Index and the interprofessional collaboration scale were compared between hospitals. RESULTS: Exploratory factor analysis revealed 3 factors in the adapted interprofessional collaboration scale - labeled Communication, Accommodation, and Isolation - which were subsequently corroborated by confirmatory factor analysis. Nurses' scale responses about physician collaboration had convergent, discriminant, and concurrent validity, and acceptable reliability. CONCLUSION: The new scale is suitable for use with nurses assessing physicians. The scale may yield valid and reliable data from physicians and others, but measurement equivalence and other properties of the scale should be investigated before it is used with multiple health professional groups. PMID- 20353578 TI - Reporting methods in studies developing prognostic models in cancer: a review. AB - BACKGROUND: Development of prognostic models enables identification of variables that are influential in predicting patient outcome and the use of these multiple risk factors in a systematic, reproducible way according to evidence based methods. The reliability of models depends on informed use of statistical methods, in combination with prior knowledge of disease. We reviewed published articles to assess reporting and methods used to develop new prognostic models in cancer. METHODS: We developed a systematic search string and identified articles from PubMed. Forty-seven articles were included that satisfied the following inclusion criteria: published in 2005; aiming to predict patient outcome; presenting new prognostic models in cancer with outcome time to an event and including a combination of at least two separate variables; and analysing data using multivariable analysis suitable for time to event data. RESULTS: In 47 studies, prospective cohort or randomised controlled trial data were used for model development in only 33% (15) of studies. In 30% (14) of the studies insufficient data were available, having fewer than 10 events per variable (EPV) used in model development. EPV could not be calculated in a further 40% (19) of the studies. The coding of candidate variables was only reported in 68% (32) of the studies. Although use of continuous variables was reported in all studies, only one article reported using recommended methods of retaining all these variables as continuous without categorisation. Statistical methods for selection of variables in the multivariate modelling were often flawed. A method that is not recommended, namely, using statistical significance in univariate analysis as a pre-screening test to select variables for inclusion in the multivariate model, was applied in 48% (21) of the studies. CONCLUSIONS: We found that published prognostic models are often characterised by both use of inappropriate methods for development of multivariable models and poor reporting. In addition, models are limited by the lack of studies based on prospective data of sufficient sample size to avoid overfitting. The use of poor methods compromises the reliability of prognostic models developed to provide objective probability estimates to complement clinical intuition of the physician and guidelines. PMID- 20353579 TI - Reporting performance of prognostic models in cancer: a review. AB - BACKGROUND: Appropriate choice and use of prognostic models in clinical practice require the use of good methods for both model development, and for developing prognostic indices and risk groups from the models. In order to assess reliability and generalizability for use, models need to have been validated and measures of model performance reported. We reviewed published articles to assess the methods and reporting used to develop and evaluate performance of prognostic indices and risk groups from prognostic models. METHODS: We developed a systematic search string and identified articles from PubMed. Forty-seven articles were included that satisfied the following inclusion criteria: published in 2005; aiming to predict patient outcome; presenting new prognostic models in cancer with outcome time to an event and including a combination of at least two separate variables; and analysing data using multivariable analysis suitable for time to event data. RESULTS: In 47 studies, Cox models were used in 94% (44), but the coefficients or hazard ratios for the variables in the final model were reported in only 72% (34). The reproducibility of the derived model was assessed in only 11% (5) of the articles. A prognostic index was developed from the model in 81% (38) of the articles, but researchers derived the prognostic index from the final prognostic model in only 34% (13) of the studies; different coefficients or variables from those in the final model were used in 50% (19) of models and the methods used were unclear in 16% (6) of the articles. Methods used to derive prognostic groups were also poor, with researchers not reporting the methods used in 39% (14 of 36) of the studies and data derived methods likely to bias estimates of differences between risk groups being used in 28% (10) of the studies. Validation of their models was reported in only 34% (16) of the studies. In 15 studies validation used data from the same population and in five studies from a different population. Including reports of validation with external data from publications up to four years following model development, external validation was attempted for only 21% (10) of models. Insufficient information was provided on the performance of models in terms of discrimination and calibration. CONCLUSIONS: Many published prognostic models have been developed using poor methods and many with poor reporting, both of which compromise the reliability and clinical relevance of models, prognostic indices and risk groups derived from them. PMID- 20353581 TI - Evidence for a lineage of virulent bacteriophages that target Campylobacter. AB - BACKGROUND: Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. RESULTS: Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. CONCLUSIONS: Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time. PMID- 20353582 TI - Effects of mode of administration (MOA) on the measurement properties of the EORTC QLQ-C30: a randomized study. AB - BACKGROUND: While modern electronic data collection methods (e.g., computer touch screen or web-based) hold much promise, most current studies continue to make use of more traditional data collection techniques, including paper-and-pencil administration and telephone interviews. The present randomized trial investigated the measurement properties of the EORTC QLQ-C30 under three different modes of administration (MOA's). METHODS: A heterogeneous sample of 314 cancer patients undergoing treatment at a specialized treatment center in Amsterdam were randomized to one of three MOA's for the QLQ-C30: paper-and-pencil at home via the mail, telephone interview, and paper-and-pencil at the hospital clinic. Group differences in internal consistency reliabilities (Cronbach's alpha coefficient) for the scale scores were compared. Differences in mean scale scores were also compared by means of ANOVA, with adjustment for potential confounders. RESULTS: Only one statistically significant, yet minor, difference in Cronbach's alpha between the MOA groups was observed for the Role Functioning scale (all 3 alphas >0.80). Significant differences in group means -after adjustment- were found for the Emotional Functioning (EF) scale. Patients completing the written questionnaire at home had significantly lower levels of EF as compared to those interviewed via the telephone; EF scores of those completing the questionnaire at the clinic fell in-between those of the other two groups. These differences, however, were small in magnitude. CONCLUSIONS: MOA had little effect on the reliability or the mean scores of the EORTC QLQ-C30, with the possible exception of the EF scale. PMID- 20353580 TI - Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. AB - INTRODUCTION: This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort. METHODS: The magnitude of association for each genotype was assessed in 1,046 RA subjects from the Yorkshire Early RA cohort and in 5,968 healthy UK controls. Additional exploratory subanalyses were undertaken in subgroups defined by autoantibody status (rheumatoid factor and anti-cyclic citrullinated peptide) or disease severity (baseline articular erosions, Health Assessment Questionnaire (HAQ) score and swollen joint count (SJC)). RESULTS: In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA. The magnitude of association for these loci was increased in those patients who were autoantibody-positive. PTPN22 was associated with autoantibody-negative RA (per-allele OR = 1.3, trend P = 0.04). There was no evidence of association between these five genetic loci and baseline erosions or SJC in the total RA cohort, after adjustment for symptom duration. TRAF1/C5 was significantly associated with baseline HAQ, however, following adjustment for symptom duration (P trend = 0.03). CONCLUSIONS: These findings support the mounting evidence that different genetic loci are associated with autoantibody positive and autoantibody-negative RA, possibly suggesting that many of the genes identified to date are associated with autoantibody production. Additional studies with a specific focus on autoantibody-negative RA will be needed to identify the genes predisposing to this RA subgroup. The TRAF1/C5 locus in particular warrants further investigation in RA as a potential disease severity locus. PMID- 20353583 TI - Elevated endotoxin levels in non-alcoholic fatty liver disease. AB - BACKGROUND: Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non alcoholic fatty liver disease (NAFLD) patients, with and without type 2 diabetes mellitus (T2DM), and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. METHODS: Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14), soluble tumour necrosis factor receptor II (sTNFRII) and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6) or diet plus Orlistat (n = 8). RESULTS: Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8) EU/mL; controls: 3.9(3.2, 5.2) EU/mL, p < 0.001); NAFLD alone produced comparable endotoxin levels to T2DM (NAFLD: T2DM: 10.6(5.6, 14.2) EU/mL; non-diabetic: 10.6(8.5, 15.2) EU/mL), whilst a significant correlation between insulin resistance and serum endotoxin was observed (r = 0.27, p = 0.008). Both sCD14 (p < 0.01) and sTNFRII (p < 0.001) increased with severity of fibrosis. A positive correlation was also noted between sTNFRII and sCD14 in the NAFLD subjects (r = 0.29, p = 0.004).Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006), weight (p = 0.005) and endotoxin (p = 0.004) compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. CONCLUSIONS: Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden. PMID- 20353584 TI - Adjuvant glycerol is not beneficial in experimental pneumococcal meningitis. AB - BACKGROUND: Bacterial meningitis in children causes high rates of mortality and morbidity. In a recent clinical trial, oral glycerol significantly reduced severe neurological sequelae in paediatric meningitis caused by Haemophilus influenzae type b, and a tendency towards a benefit of adjunctive glycerol was seen in pneumococcal meningitis. METHODS: Here we examined the effects of glycerol in pneumococcal meningitis of infant rats and adult mice. All animals received ceftriaxone, and glycerol or placebo. Brain damage, hearing loss, and inflammatory parameters were assessed. RESULTS: Clinically and by histopathology, animals treated with glycerol or placebo did not differ. While both groups showed equally high levels of matrix metalloproteinase-9 at 24 h after infection, a significant difference in favour of glycerol was observed at 40 h after infection. However, this difference in matrix metalloproteinase-9 in late disease did not result in an improvement of histopathologic parameters. CONCLUSION: No benefit of adjunctive glycerol was found in these models of pneumococcal meningitis. PMID- 20353585 TI - Efficient gene delivery and silencing of mouse and human pancreatic islets. AB - BACKGROUND: In view of the importance of beta cells in glucose homeostasis and the profound repercussions of beta cell pathology on human health, the acquisition of tools to study pancreatic islet function is essential for the design of alternative novel therapies for diabetes. One promising approach toward this goal involves the modification of gene expression profile of beta cells. RESULTS: This study describes a new method of gene and siRNA delivery into human pancreatic islets by microporation technology. We demonstrated that mild islet distention with accutase greatly enhanced the transfection efficiency without compromising in vitro function (secretion, apoptosis and viability). As an example, the recently identified gene involved in type 2 diabetes, ZnT8, can be over-expressed or silenced by RNA interference using this technology. Microporation can also be used on rodent islets. CONCLUSIONS: Taken together, our results demonstrate that microporation technology can be used to modify gene expression in whole rodent and human islets without altering their in vitro function and will be key to the elucidation of the factors responsible for proper islet function. PMID- 20353586 TI - Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy. AB - BACKGROUND: Some epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested. METHODS: We studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-<0.2, 0.2-<0.4, and > or = 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged <14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects. RESULTS: Relative risk of leukemia associated with antecedent residence in the area with exposure > or = 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies. CONCLUSIONS: Though the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation. PMID- 20353587 TI - Using epitope predictions to evaluate efficacy and population coverage of the Mtb72f vaccine for tuberculosis. AB - BACKGROUND: The Mtb72f subunit vaccine for tuberculosis, currently in clinical trials, is hoped to provide improved protection compared to the current BCG vaccine. It is not clear, however, whether Mtb72f would be equally protective in the different human populations suffering from a high burden of tuberculosis. Previous work by Hebert and colleagues demonstrated that the PPE18 protein of Mtb72f had significant variability in a sample of clinical M. tuberculosis isolates. However, whether this variation might impact the efficacy of Mtb72f in the context of the microbial and host immune system interactions remained to be determined. The present study assesses Mtb72f's predicted efficacy in people with different DRB1 genotypes to predict whether the vaccine will protect against diverse clinical strains of M. tuberculosis in a diverse host population. RESULTS: We evaluated the binding of epitopes in the vaccine to different alleles of the human DRB1 Class II MHC protein using freely available epitope prediction programs and compared protein sequences from clinical isolates to the sequences included in the Mtb72f vaccine. This analysis predicted that the Mtb72f vaccine would be less effective for several DRB1 genotypes, due either to limited vaccine epitope binding to the DRB1 proteins or to binding primarily by unconserved PPE18 epitopes. Furthermore, we found that these less-protective DRB1 alleles are found at a very high frequency in several populations with a high burden of tuberculosis. CONCLUSION: Although the Mtb72f vaccine candidate has shown promise in animal and clinical trials thus far, it may not be optimally effective in some genotypic backgrounds. Due to variation in both M. tuberculosis protein sequences and epitope-binding capabilities of different HLA alleles, certain human populations with a high burden of tuberculosis may not be optimally protected by the Mtb72f vaccine. The efficacy of the Mtb72f vaccine should be further examined in these particular populations to determine whether additional protective measures might be necessary for these regions. PMID- 20353588 TI - No effect of epoprostenol on right ventricular diameter in patients with acute pulmonary embolism: a randomized controlled trial. AB - BACKGROUND: Right ventricular dilatation in the setting of acute pulmonary embolism is associated with an adverse prognosis. Treatment with a pulmonary vasodilator has never been studied systematically. We evaluated the effect of epoprostenol on right ventricular diameter and function in patients with acute pulmonary embolism and right ventricular dilatation. METHODS: In a randomized, single-blind study, 14 patients with acute pulmonary embolism received epoprostenol or placebo infusion for 24 hours on top of conventional treatment. Effects on right ventricular end-diastolic diameter, systolic pulmonary artery pressure, right ventricle fractional area change and tricuspid annular plane systolic excursion were assessed by serial echocardiography. Furthermore Troponin T and NT-proBNP were measured serially. RESULTS: Compared to placebo, epoprostenol was associated with a relative change from baseline in right ventricular end-diastolic diameter of +2% after 2.5 hours and -8% after 24 hours. Epoprostenol did not have a significant effect on systolic pulmonary artery pressure, right ventricular fractional area change and tricuspid annular plane systolic excursion, nor on biochemical parameters. CONCLUSION: In patients with acute pulmonary embolism and right ventricular overload, treatment with epoprostenol did not improve right ventricular dilatation or any other measured variables of right ventricular overload. TRIAL REGISTRATION: REGISTRATION: URL: NCT01014156Medical ethical committee: Medisch-ethische toetsingscommissie (METc) from the VUmc (free university medical centre). PMID- 20353589 TI - A thalamic reticular networking model of consciousness. AB - [BACKGROUND]: It is reasonable to consider the thalamus a primary candidate for the location of consciousness, given that the thalamus has been referred to as the gateway of nearly all sensory inputs to the corresponding cortical areas. Interestingly, in an early stage of brain development, communicative innervations between the dorsal thalamus and telencephalon must pass through the ventral thalamus, the major derivative of which is the thalamic reticular nucleus (TRN). The TRN occupies a striking control position in the brain, sending inhibitory axons back to the thalamus, roughly to the same region where they receive afferents. [HYPOTHESES]: The present study hypothesizes that the TRN plays a pivotal role in dynamic attention by controlling thalamocortical synchronization. The TRN is thus viewed as a functional networking filter to regulate conscious perception, which is possibly embedded in thalamocortical networks. Based on the anatomical structures and connections, modality-specific sectors of the TRN and the thalamus appear to be responsible for modality-specific perceptual representation. Furthermore, the coarsely overlapped topographic maps of the TRN appear to be associated with cross-modal or unitary conscious awareness. Throughout the latticework structure of the TRN, conscious perception could be accomplished and elaborated through accumulating intercommunicative processing across the first-order input signal and the higher-order signals from its functionally associated cortices. As the higher-order relay signals run cumulatively through the relevant thalamocortical loops, conscious awareness becomes more refined and sophisticated. [CONCLUSIONS]: I propose that the thalamocortical integrative communication across first- and higher-order information circuits and repeated feedback looping may account for our conscious awareness. This TRN-modulation hypothesis for conscious awareness provides a comprehensive rationale regarding previously reported psychological phenomena and neurological symptoms such as blindsight, neglect, the priming effect, the threshold/duration problem, and TRN-impairment resembling coma. This hypothesis can be tested by neurosurgical investigations of thalamocortical loops via the TRN, while simultaneously evaluating the degree to which conscious perception depends on the severity of impairment in a TRN-modulated network. PMID- 20353591 TI - Functional genomics of mountain pine beetle (Dendroctonus ponderosae) midguts and fat bodies. AB - BACKGROUND: The mountain pine beetle (Dendroctonus ponderosae) is a significant coniferous forest pest in western North America. It relies on aggregation pheromones to colonize hosts. Its three major pheromone components, trans verbenol, exo-brevicomin, and frontalin, are thought to arise via different metabolic pathways, but the enzymes involved have not been identified or characterized. We produced ESTs from male and female midguts and associated fat bodies and used custom oligonucleotide microarrays to study gene expression patterns and thereby made preliminary identification of pheromone-biosynthetic genes. RESULTS: Clones from two un-normalized cDNA libraries were directionally sequenced from the 5' end to yield 11,775 ESTs following sequence cleansing. The average read length was 550 nt. The ESTs clustered into 1,201 contigs and 2,833 singlets (4,034 tentative unique genes). The ESTs are broadly distributed among GO functional groups, suggesting they reflect a broad spectrum of the transcriptome. Among the most represented genes are representatives of sugar digesting enzymes and members of an apparently Scolytid-specific gene family of unknown function. Custom NimbleGen 4-plex arrays representing the 4,034 tentative unique genes were queried with RNA from eleven different biological states representing larvae, pupae, and midguts and associated fat bodies of unfed or fed adults. Quantitative (Real-Time) RT-PCR (qRT-PCR) experiments confirmed that the microarray data accurately reflect expression levels in the different samples. Candidate genes encoding enzymes involved in terminal steps of biosynthetic pathways for exo-brevicomin and frontalin were tentatively identified. CONCLUSIONS: These EST and microarray data are the first publicly-available functional genomics resources for this devastating forestry pest. PMID- 20353590 TI - Characterization of protein tyrosine phosphatase H1 knockout mice in animal models of local and systemic inflammation. AB - BACKGROUND: PTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial. PTPH1 dephosphorylates TCRzeta in vitro, inhibiting the downstream inflammatory signaling pathway, however no immunological phenotype has been detected in primary T cells derived from PTPH1 KO mice. The aim of the present study is to characterize PTPH1 phenotype in two in vivo inflammatory models and to give insights in possible PTPH1 functions in cytokine release. METHODS: We challenged PTPH1-KO mice with two potent immunomodulatory molecules, carrageenan and LPS, in order to determine PTPH1 possible role in inflammatory response in vivo. Cytokine release, inflammatory pain and gene expression were investigated in challenged PTPH1-WT and KO mice. RESULTS: The present study shows that carrageenan induces a trend of slightly increased spontaneous pain sensitivity in PTPH1-KO mice compared to WT (wild type) littermates, but no differences in cytokine release, induced pain perception and cellular infiltration have been detected between the two genotypes in this mouse model. On the other hand, LPS-induced TNFalpha, MCP-1 and IL10 release was significantly reduced in PTPH1-KO plasma compared to WTs 30 and 60 minutes post challenge. No cytokine release modulation was detectable 180 minutes post LPS challenge. CONCLUSION: In conclusion, the present study points out a slight potential role for PTPH1 in spontaneous pain sensitivity and it indicates that this phosphatase might play a role in the positive regulation of the LPS induced cytokines release in vivo, in contrast to previous reports indicating PTPH1 as potential negative regulator of immune response. PMID- 20353592 TI - Abuse and mental disorders among women at walk-in clinics in Trinidad: a cross sectional study. AB - BACKGROUND: To determine the prevalence of abuse by their partners and its association with mental disorders among female patients at walk-in clinics in Trinidad. METHODS: Female participants from 16 randomly selected walk-in clinics, previously stratified to represent all administrative regions and urban and rural settings, who were 18 years or older, were surveyed during May to August 2007 using the WAST-Short and PRIME-MD questionnaires. RESULTS: 432 women participated (a 92% response rate), Of these 16% were aged 20-29, 11.8% 30-39 and 19% 40-49; 37% were married, 25% single; 44.7% were Indo- and 35% Afro-Trinidadian; 67.8% had achieved education up to age 14 only. 30.3% were employed and 3.0% reported incomes more than $5,001 TTD (Trinidad and Tobago Dollars) per month. Forty percent (173) of all respondents were positive for abuse as scored by the WAST Short scale. Chi-square analysis suggested associations (p < 0.05) between abuse and age, employment status, being in a current relationship, and having the desire to cut down on alcohol intake. Further there were associations between abuse and the presence of depression, suicidal ideation, post-traumatic stress disorder and somatization as determined by the PRIME-MD scale. Logistic regression showed that the statistically significant (p < 0.05) predictors of woman abuse were age less than 49, wanting to cut down on alcohol use and currently being in a relationship. CONCLUSION: Among women of primarily lower socioeconomic status who attend walk-in clinics in Trinidad abuse as measured by the WAST-Short scale is high and there are statistically significant associations with mental disorders as determined by the PRIME-MD scale. PMID- 20353593 TI - Genetic modifiers of Hb E/beta0 thalassemia identified by a two-stage genome-wide association study. AB - BACKGROUND: Patients with Hb E/beta0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/beta0 thalassemia and normal alpha globin genes. METHODS: First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping. RESULTS: After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the beta-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 x 10(-13)). Seven SNPs in two distinct LD blocks within a region centromeric to the beta-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 x 10(-11)). Several previously unreported SNPs were also significantly associated with disease severity. CONCLUSIONS: These results suggest that there may be an additional regulatory region centromeric to the beta-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression. PMID- 20353594 TI - Building and analyzing protein interactome networks by cross-species comparisons. AB - BACKGROUND: A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast) and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species. RESULTS: The connectivity of the resultant networks was determined to have scale-free distribution, small world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced. CONCLUSIONS: Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org provides research biologists intuitive access to this data. PMID- 20353596 TI - Regulation of PCNA polyubiquitination in human cells. AB - BACKGROUND: The ubiquitin-based molecular switch dictating error free versus error prone repair has been conserved throughout eukaryotic evolution. A central component of this switch is the homotrimeric clamp PCNA, which is ubiquitinated in response to genotoxic stress allowing recovery of replication forks blocked at sites of DNA damage. The particulars of PCNA ubiquitination have been elucidated in yeast and to a further extent recently in human cells. However, gaps in the detailed mechanism and regulation of PCNA polyubiquitination still persist in human cells. FINDINGS: We expand upon several studies and show that PCNA is polyubiquitnated in normal skin fibroblasts, and that this ubiquitination is dependant on RAD18. Furthermore we define the types of DNA damage that induce ubiquitination on PCNA. Cisplatin, methylmethane sulphonate and benzo(a)pyrene diol-epoxide induce the polyubiquitination of PCNA to the same extent as UV while polyubiquitination is not detected after X-ray treatment. Moreover, we show that ubiquitination of PCNA is not regulated by cell cycle checkpoint kinases ATM-Chk2 or ATR-Chk1. Significantly, we report that PCNA polyubiquitination is negatively regulated by USP1. CONCLUSIONS: Our results demonstrate the importance of PCNA polyubiquitination in human cells and define the key regulator of this ubiquitination. PMID- 20353595 TI - Genomic organization of duplicated short wave-sensitive and long wave-sensitive opsin genes in the green swordtail, Xiphophorus helleri. AB - BACKGROUND: Long wave-sensitive (LWS) opsin genes have undergone multiple lineage specific duplication events throughout the evolution of teleost fishes. LWS repertoire expansions in live-bearing fishes (family Poeciliidae) have equipped multiple species in this family with up to four LWS genes. Given that color vision, especially attraction to orange male coloration, is important to mate choice within poeciliids, LWS opsins have been proposed as candidate genes driving sexual selection in this family. To date the genomic organization of these genes has not been described in the family Poeciliidae, and little is known about the mechanisms regulating the expression of LWS opsins in any teleost. RESULTS: Two BAC clones containing the complete genomic repertoire of LWS opsin genes in the green swordtail fish, Xiphophorus helleri, were identified and sequenced. Three of the four LWS loci identified here were linked in a tandem array downstream of two tightly linked short wave-sensitive 2 (SWS2) opsin genes. The fourth LWS opsin gene, containing only a single intron, was not linked to the other three and is the product of a retrotransposition event. Genomic and phylogenetic results demonstrate that the LWS genes described here share a common evolutionary origin with those previously characterized in other poeciliids. Using qualitative RT-PCR and MSP we showed that each of the LWS and SWS2 opsins, as well as three other cone opsin genes and a single rod opsin gene, were expressed in the eyes of adult female and male X. helleri, contributing to six separate classes of adult retinal cone and rod cells with average lambdamax values of 365 nm, 405 nm, 459 nm, 499 nm, 534 nm and 568 nm. Comparative genomic analysis identified two candidate teleost opsin regulatory regions containing putative CRX binding sites and hormone response elements in upstream sequences of LWS gene regions of seven teleost species, including X. helleri. CONCLUSIONS: We report the first complete genomic description of LWS and SWS2 genes in poeciliids. These data will serve as a reference for future work seeking to understand the relationship between LWS opsin genomic organization, gene expression, gene family evolution, sexual selection and speciation in this fish family. PMID- 20353597 TI - Bulk elastic properties of chicken embryos during somitogenesis. AB - We present measurements of the bulk Young's moduli of early chick embryos at Hamburger-Hamilton stage 10. Using a micropipette probe with a force constant k approximately 0.025 N/m, we applied a known force in the plane of the embryo in the anterior-posterior direction and imaged the resulting tissue displacements. We used a two-dimensional finite-element simulation method to model the embryo as four concentric elliptical elastic regions with dimensions matching the embryo's morphology. By correlating the measured tissue displacements to the displacements calculated from the in-plane force and the model, we obtained the approximate short time linear-elastic Young's moduli: 2.4 +/- 0.1 kPa for the midline structures (notocord, neural tube, and somites), 1.3 +/- 0.1 kPa for the intermediate nearly acellular region between the somites and area pellucida, 2.1 +/- 0.1 kPa for the area pellucida, and 11.9 +/- 0.8 kPa for the area opaca. PMID- 20353598 TI - Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure. AB - BACKGROUND: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen induced ALF. METHOD: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. RESULTS: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n = 4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg), increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min) and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome.Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02) and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14) coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. CONCLUSION: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems. PMID- 20353599 TI - Barriers to tuberculosis care: a qualitative study among Somali pastoralists in Ethiopia. AB - BACKGROUND: At the dawn of the third millennium, while the control of the second biggest infectious killer in the world (tuberculosis [TB]) is an international priority, millions of pastoralist communities in the Horn of Africa are struggling to access TB care. Prompt diagnosis and treatment of pastoralist TB patients remain to be a challenge in TB control programs in many countries in this region, where pastoralism is a common means of livelihood. Better understanding of community perceptions of TB and its management could help identify reasons for the delay in diagnosis of TB among pastoral communities. The aim of this study is to explore barriers delaying diagnosis among pastoralist TB patients in the Somali Regional State (SRS) of Ethiopia. METHODS: A qualitative study, including 19 respondents was conducted in the SRS of Ethiopia. Participatory Rural Appraisal (PRA) and informal interview techniques were employed to explore pastoralists' migration patterns, their perceptions of TB and their access to TB services. The influence of these factors on the delay of TB patients in receiving biomedical diagnosis was then assessed. RESULTS: We found that lack of access to formal health services as well as traditional beliefs leading to self treatment were barriers to prompt bio-medical diagnosis of TB among pastoralist TB patients in the SRS of Ethiopia. This study highlights that limited access to TB control programs is the most important barrier in early seeking of biomedical diagnosis of TB among pastoral communities with nomadic pastoralist being the most affected. CONCLUSIONS: Diagnostic and treatment facilities should be established in strategic villages that pastoralist can reach in both dry and wet seasons. Such facilities may alleviate the observed long distance to health facilities and thus long delay in diagnosis of TB. This strategy should be compounded with a community based TB control approach, whereby basic medical training on TB management such as provision of health education, drug distribution and observations is provided to local traditional healers and religious leaders. This approach may improve pastoralists' perceptions of TB, hence eliminating the observed traditional believes associated with TB in pastoralists' context of the SRS. PMID- 20353600 TI - Deformation analysis of 3D tagged cardiac images using an optical flow method. AB - BACKGROUND: This study proposes and validates a method of measuring 3D strain in myocardium using a 3D Cardiovascular Magnetic Resonance (CMR) tissue-tagging sequence and a 3D optical flow method (OFM). METHODS: Initially, a 3D tag MR sequence was developed and the parameters of the sequence and 3D OFM were optimized using phantom images with simulated deformation. This method then was validated in-vivo and utilized to quantify normal sheep left ventricular functions. RESULTS: Optimizing imaging and OFM parameters in the phantom study produced sub-pixel root-mean square error (RMS) between the estimated and known displacements in the x (RMSx = 0.62 pixels (0.43 mm)), y (RMSy = 0.64 pixels (0.45 mm)) and z (RMSz = 0.68 pixels (1 mm)) direction, respectively. In-vivo validation demonstrated excellent correlation between the displacement measured by manually tracking tag intersections and that generated by 3D OFM (R >or= 0.98). Technique performance was maintained even with 20% Gaussian noise added to the phantom images. Furthermore, 3D tracking of 3D cardiac motions resulted in a 51% decrease in in-plane tracking error as compared to 2D tracking. The in-vivo function studies showed that maximum wall thickening was greatest in the lateral wall, and increased from both apex and base towards the mid-ventricular region. Regional deformation patterns are in agreement with previous studies on LV function. CONCLUSION: A novel method was developed to measure 3D LV wall deformation rapidly with high in-plane and through-plane resolution from one 3D cine acquisition. PMID- 20353601 TI - A clustered set of three Sp-family genes is ancestral in the Metazoa: evidence from sequence analysis, protein domain structure, developmental expression patterns and chromosomal location. AB - BACKGROUND: The Sp-family of transcription factors are evolutionarily conserved zinc finger proteins present in many animal species. The orthology of the Sp genes in different animals is unclear and their evolutionary history is therefore controversially discussed. This is especially the case for the Sp gene buttonhead (btd) which plays a key role in head development in Drosophila melanogaster, and has been proposed to have originated by a recent gene duplication. The purpose of the presented study was to trace orthologs of btd in other insects and reconstruct the evolutionary history of the Sp genes within the metazoa. RESULTS: We isolated Sp genes from representatives of a holometabolous insect (Tribolium castaneum), a hemimetabolous insect (Oncopeltus fasciatus), primitively wingless hexapods (Folsomia candida and Thermobia domestica), and an amphipod crustacean (Parhyale hawaienis). We supplemented this data set with data from fully sequenced animal genomes. We performed phylogenetic sequence analysis with the result that all Sp factors fall into three monophyletic clades. These clades are also supported by protein domain structure, gene expression, and chromosomal location. We show that clear orthologs of the D. melanogaster btd gene are present even in the basal insects, and that the Sp5-related genes in the genome sequence of several deuterostomes and the basal metazoans Trichoplax adhaerens and Nematostella vectensis are also orthologs of btd. CONCLUSIONS: All available data provide strong evidence for an ancestral cluster of three Sp-family genes as well as synteny of this Sp cluster and the Hox cluster. The ancestral Sp gene cluster already contained a Sp5/btd ortholog, which strongly suggests that btd is not the result of a recent gene duplication, but directly traces back to an ancestral gene already present in the metazoan ancestor. PMID- 20353602 TI - Explosive growth of facet joint interventions in the Medicare population in the United States: a comparative evaluation of 1997, 2002, and 2006 data. AB - BACKGROUND: The Office of Inspector General of the Department of Health and Human Services (OIG-DHHS) issued a report which showed explosive growth and also raised questions of lack of medical necessity and/or indications for facet joint injection services in 2006.The purpose of the study was to determine trends of frequency and cost of facet joint interventions in managing spinal pain. METHODS: This analysis was performed to determine trends of frequency and cost of facet jointInterventions in managing spinal pain, utilizing the annual 5% national sample of the Centers forMedicare and Medicaid Services (CMS) for 1997, 2002, and 2006.Outcome measures included overall characteristics of Medicare beneficiaries receiving facet joint interventions, utilization of facet joint interventions by place of service, by specialty, reimbursement characteristics, and other variables. RESULTS: From 1997 to 2006, the number of patients receiving facet joint interventions per 100,000Medicare population increased 386%, facet joint visits increased 446%, and facet joint interventions increased 543%. The increases were higher in patients aged less than 65 years compared to those 65 or older with patients increasing 504% vs. 355%, visits increasing 587% vs. 404%, and services increasing 683% vs. 498%.Total expenditures for facet joint interventions in the Medicare population increased from over $229 million in 2002 to over $511 million in 2006, with an overall increase of 123%. In 2006, there was a 26.8-fold difference in utilization of facet joint intervention services in Florida compared to the state with the lowest utilization - Hawaii.There was an annual increase of 277.3% in the utilization of facet joint interventions by general physicians, whereas a 99.5% annual increase was seen for nurse practitioners (NPs) and certified registered nurse anesthetists (CRNAs) from 2002 to 2006. Further, in Florida, 47% of facet joint interventions were performed by general physicians. CONCLUSIONS: The reported explosive growth of facet joint interventions in managing spinal pain in certain regions and by certain specialties may result in increased regulations and scrutiny with reduced access. PMID- 20353603 TI - Knowledge-guided gene ranking by coordinative component analysis. AB - BACKGROUND: In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data. RESULTS: To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers. CONCLUSION: We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification. PMID- 20353604 TI - A full-length enriched cDNA library and expressed sequence tag analysis of the parasitic weed, Striga hermonthica. AB - BACKGROUND: The obligate parasitic plant witchweed (Striga hermonthica) infects major cereal crops such as sorghum, maize, and millet, and is the most devastating weed pest in Africa. An understanding of the nature of its parasitism would contribute to the development of more sophisticated management methods. However, the molecular and genomic resources currently available for the study of S. hermonthica are limited. RESULTS: We constructed a full-length enriched cDNA library of S. hermonthica, sequenced 37,710 clones from the library, and obtained 67,814 expressed sequence tag (EST) sequences. The ESTs were assembled into 17,317 unigenes that included 10,319 contigs and 6,818 singletons. The S. hermonthica unigene dataset was subjected to a comparative analysis with other plant genomes or ESTs. Approximately 80% of the unigenes have homologs in other dicotyledonous plants including Arabidopsis, poplar, and grape. We found that 589 unigenes are conserved in the hemiparasitic Triphysaria species but not in other plant species. These are good candidates for genes specifically involved in plant parasitism. Furthermore, we found 1,445 putative simple sequence repeats (SSRs) in the S. hermonthica unigene dataset. We tested 64 pairs of PCR primers flanking the SSRs to develop genetic markers for the detection of polymorphisms. Most primer sets amplified polymorphicbands from individual plants collected at a single location, indicating high genetic diversity in S. hermonthica. We selected 10 primer pairs to analyze S. hermonthica harvested in the field from different host species and geographic locations. A clustering analysis suggests that genetic distances are not correlated with host specificity. CONCLUSIONS: Our data provide the first extensive set of molecular resources for studying S. hermonthica, and include EST sequences, a comparative analysis with other plant genomes, and useful genetic markers. All the data are stored in a web-based database and freely available. These resources will be useful for genome annotation, gene discovery, functional analysis, molecular breeding, epidemiological studies, and studies of plant evolution. PMID- 20353605 TI - High frequency of lactose intolerance in a prehistoric hunter-gatherer population in northern Europe. AB - BACKGROUND: Genes and culture are believed to interact, but it has been difficult to find direct evidence for the process. One candidate example that has been put forward is lactase persistence in adulthood, i.e. the ability to continue digesting the milk sugar lactose after childhood, facilitating the consumption of raw milk. This genetic trait is believed to have evolved within a short time period and to be related with the emergence of sedentary agriculture. RESULTS: Here we investigate the frequency of an allele (-13910*T) associated with lactase persistence in a Neolithic Scandinavian population. From the 14 individuals originally examined, 10 yielded reliable results. We find that the T allele frequency was very low (5%) in this Middle Neolithic hunter-gatherer population, and that the frequency is dramatically different from the extant Swedish population (74%). CONCLUSIONS: We conclude that this difference in frequency could not have arisen by genetic drift and is either due to selection or, more likely, replacement of hunter-gatherer populations by sedentary agriculturalists. PMID- 20353606 TI - Defining reference genes in Oryza sativa using organ, development, biotic and abiotic transcriptome datasets. AB - BACKGROUND: Reference genes are widely used to normalise transcript abundance data determined by quantitative RT-PCR and microarrays. However, the approaches taken to define reference genes can be variable. Although Oryza sativa (rice) is a widely used model plant and important crop specie, there has been no comprehensive analysis carried out to define superior reference genes. RESULTS: Analysis of 136 Affymetrix transcriptome datasets comprising of 373 genome microarrays from studies in rice that encompass tissue, developmental, abiotic, biotic and hormonal transcriptome datasets identified 151 genes whose expression was considered relatively stable under all conditions. A sub-set of 12 of these genes were validated by quantitative RT-PCR and were seen to be stable under a number of conditions. All except one gene that has been previously proposed as a stably expressed gene for rice, were observed to change significantly under some treatment. CONCLUSION: A new set of reference genes that are stable across tissue, development, stress and hormonal treatments have been identified in rice. This provides a superior set of reference genes for future studies in rice. It confirms the approach of mining large scale datasets as a robust method to define reference genes, but cautions against using gene orthology or counterparts of reference genes in other plant species as a means of defining reference genes. PMID- 20353607 TI - Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney. AB - BACKGROUND: Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups). RESULTS: The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group. CONCLUSIONS: It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina. PMID- 20353608 TI - Exon-primed intron-crossing (EPIC) markers for non-model teleost fishes. AB - BACKGROUND: Exon-primed intron-crossing (EPIC) markers have three advantages over anonymous genomic sequences in studying evolution of natural populations. First, the universal primers designed in exon regions can be applied across a broad taxonomic range. Second, the homology of EPIC-amplified sequences can be easily determined by comparing either their exon or intron portion depending on the genetic distance between the taxa. Third, having both the exon and intron fragments could help in examining genetic variation at the intraspecific and interspecific level simultaneously, particularly helpful when studying species complex. However, the paucity of EPIC markers has hindered multilocus studies using nuclear gene sequences, particularly in teleost fishes. RESULTS: We introduce a bioinformatics pipeline for developing EPIC markers by comparing the whole genome sequences between two or more species. By applying this approach on five teleost fishes whose genomes were available in the Ensembl database http://www.ensembl.org, we identified 210 EPIC markers that have single-copy and conserved exon regions with identity greater than 85% among the five teleost fishes. We tested 12 randomly chosen EPIC markers in nine teleost species having a wide phylogenetic range. The success rate of amplifying and sequencing those markers varied from 44% to 100% in different species. We analyzed the exon sequences of the 12 EPIC markers from 13 teleosts. The resulting phylogeny contains many traditionally well-supported clades, indicating the usefulness of the exon portion of EPIC markers in reconstructing species phylogeny, in addition to the value of the intron portion of EPIC markers in interrogating the population history. CONCLUSIONS: This study illustrated an effective approach to develop EPIC markers in a taxonomic group, where two or more genome sequences are available. The markers identified could be amplified across a broad taxonomic range of teleost fishes. The phylogenetic utility of individual markers varied according to intron size and amplifiability. The bioinformatics pipelines developed are readily adapted to other taxonomic groups. PMID- 20353609 TI - Circadian rhythm and its role in malignancy. AB - Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer. PMID- 20353611 TI - The psychometric properties of three self-report screening instruments for identifying frail older people in the community. AB - BACKGROUND: Frailty is highly prevalent in older people. Its serious adverse consequences, such as disability, are considered to be a public health problem. Therefore, disability prevention in community-dwelling frail older people is considered to be a priority for research and clinical practice in geriatric care. With regard to disability prevention, valid screening instruments are needed to identify frail older people in time. The aim of this study was to evaluate and compare the psychometric properties of three screening instruments: the Groningen Frailty Indicator (GFI), the Tilburg Frailty Indicator (TFI) and the Sherbrooke Postal Questionnaire (SPQ). For validation purposes the Groningen Activity Restriction Scale (GARS) was added. METHODS: A questionnaire was sent to 687 community-dwelling older people (> or = 70 years). Agreement between instruments, internal consistency, and construct validity of instruments were evaluated and compared. RESULTS: The response rate was 77%. Prevalence estimates of frailty ranged from 40% to 59%. The highest agreement was found between the GFI and the TFI (Cohen's kappa = 0.74). Cronbach's alpha for the GFI, the TFI and the SPQ was 0.73, 0.79 and 0.26, respectively. Scores on the three instruments correlated significantly with each other (GFI - TFI, r = 0.87; GFI - SPQ, r = 0.47; TFI - SPQ, r = 0.42) and with the GARS (GFI - GARS, r = 0.57; TFI - GARS, r = 0.61; SPQ - GARS, r = 0.46). The GFI and the TFI scores were, as expected, significantly related to age, sex, education and income. CONCLUSIONS: The GFI and the TFI showed high internal consistency and construct validity in contrast to the SPQ. Based on these findings it is not yet possible to conclude whether the GFI or the TFI should be preferred; data on the predictive values of both instruments are needed. The SPQ seems less appropriate for postal screening of frailty among community-dwelling older people. PMID- 20353610 TI - Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes. AB - BACKGROUND: To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set). METHODS: Type 2 diabetes subjects with CRI (serum creatinine > or =3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of > or = 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely--ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes. RESULTS: Single nucleotide polymorphisms -429 T>C in RAGE and rs7725 C>T SNP in 3' UTR in GFPT2 gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in GFPT2 was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor TGF-beta1 (investigated using the same sample set and reported elsewhere) and GFPT2 genotype was observed. CONCLUSIONS: Association of SNPs in RAGE and GFPT2 suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-beta1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-beta1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in GFPT2 implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests GFPT2 could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations. PMID- 20353612 TI - Peer role-play and standardised patients in communication training: a comparative study on the student perspective on acceptability, realism, and perceived effect. AB - BACKGROUND: To assess the student perspective on acceptability, realism, and perceived effect of communication training with peer role play (RP) and standardised patients (SP). METHODS: 69 prefinal year students from a large German medical faculty were randomly assigned to one of two groups receiving communication training with RP (N = 34) or SP (N = 35) in the course of their paediatric rotation. In both groups, training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children. Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales. RESULTS: Both forms of training were highly accepted (RP 5.32 +/- .41, SP 5.51 +/- .44, n.s.; 6 = very good, 1 = very poor) and perceived to be highly realistic (RP 5.60 +/- .38, SP 5.53 +/- .36, n.s.; 6 = highly realistic, 1 = unrealistic). Regarding perceived effects, participation was seen to be significantly more worthwhile in the SP group (RP 5.17 +/- .37, SP 5.50 +/- .43; p < .003; 6 = totally agree, 1 = don't agree at all). Both training methods were perceived as useful for training communication skills (RP 5.01 +/- .68, SP 5.34 +/- .47; 6 = totally agree; 1 = don't agree at all) and were considered to be moderately applicable for future parent-physician encounters (RP 4.29 +/- 1.08, SP 5.00 +/- .89; 6 = well prepared, 1 = unprepared), with usefulness and applicability both being rated higher in the SP group (p < .032 and p < .009). CONCLUSIONS: RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective. Both provide highly realistic training scenarios and warrant inclusion in medical curricula. Given the expense of SP, deciding which method to employ should be carefully weighed up. From the perspective of the students in our study, SP were seen as a more useful and more applicable tool than RP. We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective. PMID- 20353614 TI - Cognitive architectures and language acquisition: a case study in pronoun comprehension. AB - In this paper we discuss a computational cognitive model of children's poor performance on pronoun interpretation (the so-called Delay of Principle B Effect, or DPBE). This cognitive model is based on a theoretical account that attributes the DPBE to children's inability as hearers to also take into account the speaker's perspective. The cognitive model predicts that child hearers are unable to do so because their speed of linguistic processing is too limited to perform this second step in interpretation. We tested this hypothesis empirically in a psycholinguistic study, in which we slowed down the speech rate to give children more time for interpretation, and in a computational simulation study. The results of the two studies confirm the predictions of our model. Moreover, these studies show that embedding a theory of linguistic competence in a cognitive architecture allows for the generation of detailed and testable predictions with respect to linguistic performance. PMID- 20353613 TI - Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes. AB - BACKGROUND: Skeletal muscle insulin resistance (IR) is considered a critical component of type II diabetes, yet to date IR has evaded characterization at the global gene expression level in humans. MicroRNAs (miRNAs) are considered fine scale rheostats of protein-coding gene product abundance. The relative importance and mode of action of miRNAs in human complex diseases remains to be fully elucidated. We produce a global map of coding and non-coding RNAs in human muscle IR with the aim of identifying novel disease biomarkers. METHODS: We profiled >47,000 mRNA sequences and >500 human miRNAs using gene-chips and 118 subjects (n = 71 patients versus n = 47 controls). A tissue-specific gene-ranking system was developed to stratify thousands of miRNA target-genes, removing false positives, yielding a weighted inhibitor score, which integrated the net impact of both up- and down-regulated miRNAs. Both informatic and protein detection validation was used to verify the predictions of in vivo changes. RESULTS: The muscle mRNA transcriptome is invariant with respect to insulin or glucose homeostasis. In contrast, a third of miRNAs detected in muscle were altered in disease (n = 62), many changing prior to the onset of clinical diabetes. The novel ranking metric identified six canonical pathways with proven links to metabolic disease while the control data demonstrated no enrichment. The Benjamini-Hochberg adjusted Gene Ontology profile of the highest ranked targets was metabolic (P < 7.4 x 10-8), post-translational modification (P < 9.7 x 10-5) and developmental (P < 1.3 x 10 6) processes. Protein profiling of six development-related genes validated the predictions. Brain-derived neurotrophic factor protein was detectable only in muscle satellite cells and was increased in diabetes patients compared with controls, consistent with the observation that global miRNA changes were opposite from those found during myogenic differentiation. CONCLUSIONS: We provide evidence that IR in humans may be related to coordinated changes in multiple microRNAs, which act to target relevant signaling pathways. It would appear that miRNAs can produce marked changes in target protein abundance in vivo by working in a combinatorial manner. Thus, miRNA detection represents a new molecular biomarker strategy for insulin resistance, where micrograms of patient material is needed to monitor efficacy during drug or life-style interventions. PMID- 20353615 TI - Underweight and overweight among children in Zahedan, south-east Iran. AB - OBJECTIVE: The present study examined the prevalence of underweight and overweight in a group of primary-school children in Zahedan, south-east Iran. DESIGN: A cross-sectional study in a randomly selected population of schoolchildren. SETTING: Primary-school children in Zahedan city. SUBJECTS: A random sample of 1079 students (boys = 500 and girls = 579). Data on child's age, parental educational levels, body weight and height were collected. RESULTS: The rate of overweight/obesity among boys and girls was 8.9 % and 10.3 %, respectively; and of underweight among boys and girls was 22.8 % and 19.9 %, respectively. Prevalence of overweight increased as the boys and girls approached adolescence and it was more prevalent among girls than boys. Prevalence of overweight was directly related to maternal education in this population. CONCLUSIONS: High prevalence of underweight in young children as well as increase in the prevalence of overweight in girls and boys near adolescence are of concern. Early poor growth and subsequent rapid weight gain near to adolescent stage is related to adulthood obesity. PMID- 20353616 TI - Socio-economic status, place of residence and dietary habits among the elderly: the Mediterranean islands study. AB - OBJECTIVE: To investigate whether the socio-economic status (SES) of elderly eastern Mediterranean islanders is associated with their dietary habits, particularly with adherence to the traditional Mediterranean diet. DESIGN: Cross sectional. SETTING: Adherence to the Mediterranean diet was measured by the MedDietScore (range: 0-55), whereas SES was estimated using education and financial status. SUBJECTS: During 2005-2007, 300 men and women from Cyprus, 100 from Samothraki, 142 from Mitilini, 114 from Kefalonia, 131 from Crete, 150 from Lemnos, 150 from Corfu and 103 from Zakynthos (aged 65-100 years), free of known chronic diseases, participated in the survey. RESULTS: Multiple linear regression analysis revealed that belonging to the highest SES was associated with a higher MedDietScore (P < 0.01), after adjusting for potential sociodemographic, lifestyle, dietary and clinical confounders. A significant positive association was also found between MedDietScore and years of school (P = 0.004), as well as financial status (P = 0.001). CONCLUSIONS: Older Greek people of higher SES seem to follow a relatively healthier diet. Both education and income seem to play a role in this issue. Thus, public health policy makers should focus on people with low SES in order to improve their quality of diet and, consequently, their health status. PMID- 20353617 TI - Dietary diversity score is related to obesity and abdominal adiposity among Iranian female youth. AB - OBJECTIVE: To assess the relationship between diet and disease, consideration of whole-diet indices may be more informative than single-nutrient intake. The present study was conducted to report the relationship among dietary diversity score (DDS), obesity and abdominal adiposity among female university students. DESIGN: Cross-sectional study. SETTING: Isfahan, Iran. SUBJECTS: A representative sample of 289 healthy female students aged 18-28 years was selected randomly from Isfahan University of Medical Sciences, Iran. Usual dietary intake was assessed using a validated semi-quantitative FFQ. DDS was calculated according to the scoring of the five food groups based on the US Department of Agriculture Food Guide Pyramid. This is a score of diet variety, and shows the diversity of the consumed diet. Participants were categorised on the basis of quartile cut-off points of DDS. Potential confounders such as age, total energy intake and physical activity were considered in all the analyses. RESULTS: The means (sd) of BMI and waist circumference were 25.9 (sd 5.1) kg/m2 and 85.5 (sd 14) cm, respectively. The probability of obesity decreased with quartiles of DDS (OR among quartiles: 1.00, 0.41, 0.31 and 0.21, P = 0.03; this was the same for abdominal adiposity: 1.00, 0.55, 0.36 and 0.21, P = 0.02). Those in the lowest quartile of the DDS had the highest risk for being overweight. CONCLUSIONS: There were inverse associations among DDS, obesity and abdominal adiposity among the female students of Isfahan University. Further prospective investigations are needed to confirm this finding. PMID- 20353618 TI - Food shopping transition: socio-economic characteristics and motivations associated with use of supermarkets in a North African urban environment. AB - OBJECTIVE: In the context of the nutrition transition and associated changes in the food retail sector, to examine the socio-economic characteristics and motivations of shoppers using different retail formats (large supermarkets (LSM), medium-sized supermarkets (MSM) or traditional outlets) in Tunisia. DESIGN: Cross sectional survey (2006). Socio-economic status, type of food retailer and motivations data were collected during house visits. Associations between socio economic factors and type of retailer were assessed by multinomial regression; correspondence analysis was used to analyse declared motivations. SETTING: Peri urban area around Tunis, Tunisia, North Africa. SUBJECTS: Clustered random sample of 724 households. RESULTS: One-third of the households used LSM, two-thirds used either type of supermarket, but less than 5 % used supermarkets only. Those who shopped for food at supermarkets were of higher socio-economic status; those who used LSM were much wealthier, more often had a steady income or owned a credit card, while MSM users were more urban and had a higher level of education. Most households still frequently used traditional outlets, mostly their neighbourhood grocer. Reasons given for shopping at the different retailers were most markedly leisure for LSM, while for the neighbourhood grocer the reasons were fidelity, proximity and availability of credit (the latter even more for lower-income customers). CONCLUSIONS: The results pertain to the transition in food shopping practices in a south Mediterranean country; they should be considered in the context of growing inequalities in health linked to the nutritional transition, as they differentiate use and motivations for the choice of supermarkets v. traditional food retailers according to socio-economic status. PMID- 20353620 TI - Consensus on the competencies required for public health nutrition workforce development in Europe - the JobNut project. AB - OBJECTIVE: To assess and develop consensus among a European panel of public health nutrition stakeholders regarding the competencies required for effective public health nutrition practice and the level of proficiency required in different practice contexts. DESIGN: A modified Delphi study involving three rounds of questionnaires. SETTING: European Union. SUBJECTS: Public health nutrition workforce development stakeholders, including academics, practitioners and employers, from twenty European countries. RESULTS: A total of fifty-two expert panellists (84 % of an initial panel of sixty-two Delphi participants) completed all three rounds of the Delphi study. The panellists rated the importance of fifty-seven competency units possibly required of a public health nutritionist to effectively practice (Essential competencies). Twenty-nine of the fifty-seven competency units (51 %) met the consensus criteria (>=66.7 % agreement) at the second round of the Delphi survey, with the highest agreement for competencies clustered within the Nutrition science, Professional, Analytical and Public health services competency domains. Ratings of the level of competencies required for different levels in the workforce indicated that for a public health nutrition specialist, advanced-level competency was required across almost all the twenty-nine competencies rated as essential. There were limited differences in rating responses between academics and employer panellists throughout the Delphi study. CONCLUSIONS: Competencies identified as essential can be used to review current public health nutrition practices and provide the basis for curriculum design and re-development, continuing education and workforce quality assurance systems in Europe. These are all important tools for systematic and strategic workforce development. PMID- 20353619 TI - Soft drinks: time trends and correlates in twenty-four European countries. A cross-national study using the DAFNE (Data Food Networking) databank. AB - OBJECTIVE: To evaluate time trends in the availability of soft drinks, to identify food choices associated with their consumption and to assess the relationship between socio-economic status and daily soft drink availability in a wide range of European countries. DESIGN: Data on food and beverage availability collected through the national household budget surveys and harmonized in the DAFNE (Data Food Networking) project were used. Averages and variability of soft drink availability were estimated and tests for time trends were performed. The daily availability of food groups which appear to be correlated with that of soft drinks was further estimated. Multivariate logistic and linear regression models were applied to evaluate the association between socio-economic status and the acquisition of soft drinks. SETTING: Twenty-four European countries. SUBJECTS: Nationally representative samples of households. RESULTS: The availability of soft drinks is steadily and significantly increasing. Households in West and North Europe reported higher daily availability of soft drinks in comparison to other European regions. Soft drinks were also found to be correlated with lower availability of plant foods and milk and higher availability of meat and sugar products. Lower socio-economic status was associated with more frequent and higher availability of soft drinks in the household. CONCLUSIONS: Data collected in national samples of twenty-four European countries showed disparities in soft drink availability among socio-economic strata and European regions. The correlation of soft drinks with unfavourable dietary choices has public health implications, particularly among children and adolescents. PMID- 20353621 TI - A randomized clinical trial to examine enhancing cognitive-behavioral group therapy for obsessive-compulsive disorder with motivational interviewing and thought mapping. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by repeated and persistent attempts to control thoughts and actions with rituals. These rituals are used in order to prevent feared or personally distressing outcomes. Cognitive behavioral group therapy (CBGT) has been reported to be effective for treating OCD patients. However, about one-third (30%) of patients do not benefit from CBGT. Some of these patients do not show significant improvement and continue to use rituals following CBGT, partially because they fail to complete the exposure and ritual prevention (ERP) exercises. Consequently, it is important to motivate patients to fully engage in CBGT treatment and complete the ERP exercises. AIMS: A randomized behavioral trial examined 12 weeks of manual directed CBGT, with the addition of individual sessions of Motivational Interviewing (MI) and Thought Mapping (TM), and compared treatment outcome to the effectiveness of CBGT group alone. METHOD: Subjects were randomized (n=93) into a CBGT group or a CBGT group with MI+TM. RESULTS: When the two groups were compared, both groups reduced OCD symptoms. However, symptom reduction and remission were significantly higher in the MI+TM CBGT group. Positive outcomes were also maintained, with additional symptom reduction at the 3-month follow-up for the MI+TM CBGT group. CONCLUSIONS: Adding two individual sessions of MI and TM before CBGT successfully reduced OCD symptoms and was more effective than using CBGT group alone. PMID- 20353622 TI - Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand. AB - Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34.6% in children aged <5 years); 66 patients (3.8%) died. A recognized pathogen was identified in 42.5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16.7% of all pneumonias, 41.2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417.1/100,000 per year) and in persons aged >=50 years, influenza virus A (38.8/100,000 per year). These data can help guide health policy towards effective prevention strategies. PMID- 20353623 TI - Further mapping of quantitative trait loci for female sterility in wheat (Triticum aestivum L.). AB - Epistasis underlying fertility plays an important role in crop breeding. Although a new female sterile mutant in wheat, XND126, has been identified and a major quantitative trait locus (QTL), taf1, for the female sterility has been mapped, the genetic architecture of the female sterility needs to be further addressed. To identify the interaction involving the gene(s) controlling the female sterility, an investigation was carried out for the seed setting ratio in an F2 population derived from the cross between XND126 and Gaocheng 8901. Among 1250 simple sequence repeat (SSR) primer pairs in the whole genome, a total of 21 markers, obtained by recessive class approach, along with other ten tightly linked markers on reference maps in wheat, were used to survey 243 F2 individuals. As a result, 28 markers were mapped into five genetic linkage groups. The performance for female sterility for each F2 individual was evaluated simultaneously at the Urumqi and Huai'an experimental stations in 2006-2007. The two phenotypic datasets along with marker information were jointly analysed in the detection of QTL using penalized maximum likelihood approach. A total of six QTLs, including two main-effect QTLs, three epistatic QTLs and one environmental interaction and accounting for 0.67-24.55% of the total phenotypic variance, were identified. All estimated effects accounted for 53.26% of the total phenotypic variation. The taf1 detected in previous study was also located on the same marker interval on chromosome 2DS. These results enrich our understanding of the genetic basis of the female sterility. PMID- 20353624 TI - Rivastigmine in the treatment of delirium in older people: a pilot study. AB - BACKGROUND: Delirium is common in the elderly and is associated with high mortality and negative health outcomes. Reduced activity in the cholinergic system has been implicated in the pathogenesis of delirium. Cholinesterase inhibitors, which increase cholinergic activity, may therefore be beneficial in the treatment of delirium. METHODS: This is a double-blind, placebo-controlled randomized pilot study of the treatment of delirium with a cholinesterase inhibitor of patients admitted to hospital medical wards. Patients over the age of 65 years were identified as having delirium by the Confusion Assessment Method (CAM). Patients with delirium were randomized to receive rivastigmine 1.5 mg once a day increasing to 1.5 mg twice a day after seven days or an identical placebo (two tablets after seven days). RESULTS: Fifteen patients entered the trial; eight received rivastigmine and seven received placebo. All of the rivastigmine group, but only three of the placebo group, were negative for delirium on the CAM when they left the study and eventually discharged home. There was no significant difference in the duration of delirium between the two groups (rivastigmine group 6.3 days versus placebo group 9.9 days, p = 0.5, 95% confidence interval -15.6 8.4). CONCLUSIONS: The numbers of patients who screened positive for delirium was very small and as a result the sample size was too small to make any meaningful inferences about treatment of delirium. Despite the small numbers included in the study, there are some indicators that rivastigmine may be safe and effective in treating delirium. PMID- 20353625 TI - Traumatic experiences and post-traumatic stress disorder among elderly Germans: results of a representative population-based survey. AB - BACKGROUND: Only a few population-based studies on the epidemiology of post traumatic stress disorders (PTSDs) are available to date. Most of the existing studies are from the U.S.A. Against the background of World War II, the extent and long-term effects of war-related traumatic experiences in the German elderly population are of special interest. Nevertheless, population-based data on this topic are lacking to date. METHODS: This study examines the occurrence of traumatic experiences and the prevalence rates of PTSD according to DSM-IV and of partial PTSD in a randomly selected sample of the German general population aged 60 years and over (N = 814) using self-rating instruments. RESULTS: PTSD is apparent in 3.4%; when partial post-traumatic stress syndromes are included, a total of 7.2% of the aged population are involved. The most common individual symptoms resulting from war-induced trauma are avoidance of thoughts and feelings, sleep disturbances, distressing dreams and intrusive thoughts. The most frequently mentioned traumatic experiences of the generation examined in this study were war-related trauma experienced as children or in early adulthood during World War II. As a person's age increases, so does the prevalence of war related traumatic experiences. There are some gender differences in traumatic experiences, but not in post-traumatic symptoms. CONCLUSION: The results emphasize the importance of war-related traumatic experiences from World War II in the German elderly population and their impact on the prevalence of PTSD more than 60 years later. PMID- 20353626 TI - Credentialing dementia training: the Florida experience. AB - BACKGROUND: Florida is a leader in requiring that all direct care staff employed in assisted living, nursing homes, hospice, adult day care and home health undergo Alzheimer's disease (AD) training. Legislative requirements prescribe the curricula components and require a review of curricular content and minimum standards for the training providers. METHODS: We describe Florida's AD training program review process, and report the results of our review of 445 curricula received over four and a half years. RESULTS: On initial submission, over 90% of curricula submitted did not include learning objectives, time formats or didactic approach. During a review of content we often found inaccurate information, language that was not person-centered, and missing required training components. CONCLUSION: Form and content problems were prevalent across all curricular types. We propose the Florida credentialing program as a model to ensure that accurate and educationally sound curricula are used to train direct care workers. PMID- 20353627 TI - Improvements in English National Health Service (NHS) productivity were driven by the rollout of choice and competition. PMID- 20353628 TI - Panton-Valentine leukocidin Staphylococcus aureus osteomyelitis of the adult tibia--a case report. AB - Panton-Valentine leukocidin toxin producing Staphylococcus aureus (PVLSA) is known to be responsible for recurrent soft tissue infections and more serious invasive infections including necrotising pneumonia, pyomyositis, and osteomyelitis. Most reported cases involving musculoskeletal infection in adults are associated with methicillin-resistant S. aureus (MRSA) PVL-producing strains. We present the case of an adult male with PVL toxin-producing methicillin sensitive S. aureus (MSSA) osteomyelitis of the tibia which has not previously been described in adults and highlight issues of recognition, treatment, and surgical management of PVLSA osteomyelitis. PMID- 20353629 TI - Small bowel obstruction due to herniation into an extra-anatomical arterial bypass tunnel: a first case report. AB - INTRODUCTION: We highlight the importance of considering rarer causes of small bowel obstruction in patients presenting after extra-anatomical arterial bypass. CASE PRESENTATION: Our patient underwent a left common iliac-to-bifemoral bypass extra-anatomical graft for critical limb ischaemia. The patient developed mechanical small bowel obstruction on the 20th postoperative day. Emergency laparotomy revealed incarcerated, obstructed small bowel trapped in the graft tunnel. Recovery was satisfactory following small bowel resection. CONCLUSIONS: To the best of our knowledge, small bowel herniation into an arterial bypass graft tunnel, with successful treatment outcome, has not been reported to date. PMID- 20353630 TI - Delayed jejunal perforation following blunt abdominal trauma. AB - Jejunal perforation is a known complication of abdominal trauma. We report two cases of jejunal perforation presenting nearly 2 months following blunt injury to the abdomen and discuss possible mechanisms for delayed small bowel perforation. PMID- 20353631 TI - Co-existing fractures of the proximal humerus and humeral shaft without shoulder dislocation--a rare injury. AB - Multiple fractures of the humerus are a rare injury and usually associated with high-energy trauma. We report an unusual injury with co-existing fractures of the proximal humerus and humeral shaft without shoulder dislocation. We discuss our experience in the diagnosis and treatment of a 39-year-old man with co-existing fractures of proximal humerus and ipsilateral humeral shaft with radial nerve deficit. He was successfully managed with open reduction and fixation of the fractures. At follow-up 1 year after injury, he is back at work and has a good range of shoulder movements. The radial nerve injury is showing signs of recovery. In high-energy trauma to the shoulder, unusual fracture patterns with associated neurovascular deficits may be seen and this case report describes our experience with one such rare injury. PMID- 20353632 TI - Recurrent acute pancreatitis as the first and sole presentation of undiagnosed primary hyperparathyroidism. AB - INTRODUCTION: We highlight the pitfalls in delaying the diagnosis of primary hyperparathyroidism (pHPT) in patients with acute pancreatitis as the sole clinical presentation. Primary hyperparathyroidism is a recognised, but rare, cause of acute pancreatitis. Hypercalcaemia caused by undiagnosed pHPT may be the only causative factor of recurrent acute pancreatitis. PATIENTS AND METHODS: Three patients with multiple admissions for acute pancreatitis were diagnosed having pHPT during the work-up to identify possible causative factors. None of the patients had any other common predisposing factor for acute pancreatitis as revealed by clinical examination, blood tests and imaging. In retrospect, all had abnormally elevated calcium during previous admissions which was not further assessed. RESULTS: After diagnosis of pPTH, patients underwent bilateral neck exploration and parathyroidectomy. Histology confirmed parathyroid adenomas. The blood calcium level returned to normal and the patients remain well and asymptomatic after operation. CONCLUSIONS: The role of pHPT as a causative factor is underestimated when managing patients with acute pancreatitis, and frequently the underlying disease remains undiagnosed for a long time. Proper early diagnosis and management prevent unnecessary morbidity. PMID- 20353633 TI - Unusual cause of acute abdomen--omental infarction occurring in a child with cyclical neutropenia. AB - Omental infarction is a rare cause of acute abdomen in childhood. We describe a case of omental infarction mimicking acute appendicitis occurring in a child with cyclical neutropenia. Neutropenic enterocolitis, a serious cause of the acute abdomen, has been linked with cyclical neutropenia. In neutropenic patients, omental infarction when diagnosed pre-operatively can be managed conservatively with the focus on improving the neutrophil count. If after imaging the diagnosis is in doubt, there should be a low threshold for laparoscopy. The low incidence of omental infarction will continue to mean that it is a diagnosis made at operation for suspected appendicitis. In these cases, the infarcted tissue may be removed by the laparoscopic or open technique. PMID- 20353634 TI - Manubriosternal subluxation/dislocation can lead to manubriosternal septic arthritis in patients with kyphoscoliosis. AB - Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis. PMID- 20353635 TI - Use of an image intensifier to remove a challenging foreign body in a segmental bronchiole. AB - Aspiration of foreign bodies into the tracheobronchial tree is a common presentation in children, but less so in adults. Successful extraction depends on the type of foreign body aspirated, location of the foreign body in the tracheobronchial tree, the experience of the operator and the instrumentation available. We report on our management of a patient who presented with an aspirated foreign body. PMID- 20353636 TI - The evolution of consent. PMID- 20353637 TI - Request for Treatment: the evolution of consent. AB - INTRODUCTION: Request for Treatment (RFT) is a new approach to consent which aims to facilitate patients' understanding of their treatment and addresses some of the flaws highlighted in a literature review of current consent practice. It aims to provide a complete clinical, medicolegal, and documentary framework for consent and places patients at the centre of their care. It also provides doctors with more robust evidence that adequate consent has been obtained, and can be implemented with ease in most clinical scenarios, especially elective surgery. MATERIALS AND METHODS: A thorough critical analysis and literature review is undertaken looking at the current state of consent world-wide. For the first time, a complete documentary system for 'request for treatment' is devised including Request for Treatment forms (RFTFs) alternatively termed Patient centred Consent Forms (PCCFs). The arguments for the legal validity and other advantages of RFT are presented. CASE STUDY: A case with all the documentation of a full consent episode is provided which illustrates RFT in action, demonstrating the simplicity of implementation, and the robustness of the completed RFT form as a source of evidence for both consent and capacity. CONCLUSIONS: Request for Treatment (RFT) is a request-based model for consent that facilitates patient centred care. It has a number of advantages including unrivalled documentary evidence of consent in the patient's own handwriting and vocabulary, demonstration of capacity, ease of implementation, and a sound legal basis. For those who may wish to use it, RFT provides a useful and novel patient-centred method of consent, and is likely to protect against negligent consent practice by highlighting patient misunderstandings early and by providing irrefutable documentary evidence that consent has been gained. It may also provide a simple method by which Gillick competence can be assessed and documented. RFT forms are available for download at www.rft.org.uk. PMID- 20353638 TI - Ilizarov principles of deformity correction. AB - Ilizarov frames provide a versatile fixation system for the management of bony deformities, fractures and their complications. The frames give stability, soft tissue preservation, adjustability and functionality allowing bone to realise its full osteogenic potential. It is important that we have a clear and concise understanding of the Ilizarov principles of deformity correction to best make use of this fixation system. In this review article, the history of Ilizarov frame, the basic sciences behind it, the mechanical principles governing its use and the clinical use of the fixation system are discussed. PMID- 20353639 TI - Resection of rectal cancer: laparoscopy or open surgery? PMID- 20353640 TI - Confidence and conflicts of duty in surgery. AB - This paper offers an exploration of the right to confidentiality, considering the moral importance of private information. It is shown that the legitimate value that individuals derive from confidentiality stems from the public interest. It is re-assuring, therefore, that public interest arguments must be made to justify breaches of confidentiality. The General Medical Council's guidance gives very high importance to duties to maintain confidences, but also rightly acknowledges that, at times, there are more important duties that must be met. Nevertheless, this potential conflict of obligations may place the surgeon in difficult clinical situations, and examples of these are described, together with suggestions for resolution. PMID- 20353641 TI - Can the National Health Service Cancer Plan timeline be applied to colorectal hepatic metastases? AB - INTRODUCTION: The National Health Service (NHS) Cancer Plan guidelines recommend a maximum 2-week wait from referral to first appointment, and 2 months from referral to treatment for primary cancers. However, there are currently no guidelines available for metastatic disease. In the UK, nearly half of all colorectal cancer patients develop hepatic metastases. Timely, surgical resection offers the potential for cure. The aim of this study was to audit current practice for colorectal liver metastases in a regional hepatobiliary unit, and compare this to the NHS Cancer Plan standards for primary disease. PATIENTS AND METHODS: A retrospective review of the unit's database was performed for all hepatic metastases referrals from January 2006 to December 2008. The dates of referral, first appointment, investigations and initiation of treatment, along with patient's age and sex, were recorded on Microsoft Excel and analysed. Time was expressed as mean +/- SD in days. RESULTS: A total of 102 patients with hepatic metastases were identified. Five were excluded due to incomplete data. The average time from referral to first appointment was 10.6 +/- 9.4 days and the average time from referral to treatment was 38.5 +/- 28.6 days. Seventy-five (72.7%) had surgical intervention, of whom 37 also had chemotherapy. CONCLUSIONS: The data compare favourably to the NHS Cancer Plan guidelines for primary malignancy, demonstrating that a regional hepatobiliary unit is capable of delivering a service for colorectal liver metastases that adheres to the NHS Cancer Plan. Therefore, the NHS Cancer Plan can be applied to this cohort. PMID- 20353642 TI - Ureteric bupivicaine infusion for loin pain haematuria syndrome. AB - INTRODUCTION: Loin pain haematuria syndrome is a common problem with complications including opiate dependence. Morbidity treatments include intra ureteric capsaicin infusion, nephrectomy, autotransplantation and nephrolysis. We explored the use of flexible cystoscopic infusion of intra-ureteric bupivicaine. PATIENTS AND METHODS: Patients presenting with chronic loin pain underwent urological and nephrological evaluation. Bupivicaine (0.5%, 20 ml) was infused via an intra-ureteric catheter under flexible cystoscopic guidance. Repeat infusions were offered if indicated. RESULTS: Sixteen of 17 patients with 1-year follow-up responded and were satisfied. Twelve of these required repeat infusions (mean, 2.9 infusions). The procedures were well tolerated by all patients without adverse effects. CONCLUSIONS: Intra-ureteric bupivicaine infusion has a place in the management of patients with chronic renal pain. It offers a minimally invasive alternative to other treatments. This procedure warrants further investigation within a randomised, controlled trial setting. PMID- 20353643 TI - Cardiopulmonary arrest on arrival due to penetrating trauma. AB - INTRODUCTION: The aim of this study was to clarify the outcome of patients with cardiopulmonary arrest on arrival due to penetrating trauma (PT-CPA) and to establish the treatment strategy. PATIENTS AND METHODS: The clinical course of 29 patients with PT-CPA over the past 10 years was examined. We have taken three approaches to these patients: (i) an aggressive treatment strategy; (ii) an in hospital system supporting this aggressive resuscitation; and (iii) the pre hospital emergency medical service (EMS) system in our city. RESULTS: Although the return of spontaneous circulation (ROSC) was established in 59% of patients, only 17% survived for 7 days, 14% were discharged, and 7% were neurologically intact. Of 10 patients showing pulseless electrical activity (PEA) on the scene, ROSC was established in 100% and 30% were discharged; however, of 12 patients showing asystole, ROSC was established in 33% and no patient could be discharged. There was no difference in the time interval from the arrival at the emergency department to ROSC between discharged patients and patients who died. The time interval from collapse to arrival at the emergency department in discharged patients and patients who went to the intensive care unit was shorter than that of patients who died in the emergency department with and without ROSC. CONCLUSIONS: We cannot decide to give up and terminate resuscitation in any PT CPA patients and cannot define salvageable patients. However, our data show that 30-min resuscitation is thought to be relevant and that we should not give up on resuscitation because of the time interval without ROSC after arrival at the hospital. PMID- 20353645 TI - Single port laparoscopic cholecystectomy--overcoming technical problems. PMID- 20353646 TI - Comment on: Surgical management of Boerhaave's syndrome in a tertiary oesophagogastric centre. PMID- 20353647 TI - Comment on: Changes required to improve CEA outcomes. PMID- 20353648 TI - Comment on: Predicting operative mortality in patients undergoing coronary artery bypass surgery. PMID- 20353649 TI - Comment on: Clarity of language. PMID- 20353650 TI - Comment on: Appropriateness of study design. PMID- 20353651 TI - Comment on: Indications for tonsillectomy. PMID- 20353652 TI - Health informatics: what's in a name? PMID- 20353653 TI - A review of effective methods of delivery of care: skill-mix and service transfer to primary care settings. AB - AIMS: Health policy in England is seeking to minimise hospital use and provide access to services in a primary healthcare setting and maximise skill-mix, driven by issues such as cost and access. The aim of this review was to determine the effectiveness of increased use of skill-mix and service transfer within general and oral healthcare. Secondary outcome measures were related to cost, quality, access, health outcomes and satisfaction. METHODS: Data sources were the Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination DARE, British Nursing Index, CINAHL, EMBASE, MEDLINE, and PsycINFO from 1996 to August 2008. The reference lists of relevant papers were scanned to identify additional studies. DATA SELECTION: A rapid appraisal of systematic reviews, randomised controlled trials, controlled trials and service evaluations in relation to specialist services, practitioners with a special interest, medical and dental, nursing and dental care professionals, together with evidence of service shifts from secondary to primary care was undertaken. RESULTS: A total of 206 papers were reviewed. All titles and abstracts of articles and papers found were extracted and validated according to predefined criteria. They were screened for relevance by two researchers, who assessed trial quality and extracted data. Twenty-six papers met the inclusion criteria. The literature demonstrated limited evidence of the cost-effectiveness and health outcomes associated with changes in setting and skill-mix. However, there was evidence of improved access, patient and professional satisfaction. CONCLUSIONS: There is an overwhelming need for well-designed interventions with robust evaluation to examine cost-effectiveness and benefits to patients and the health workforce. PMID- 20353654 TI - Primary care clinicians and the detection and referral of potentially malignant disorders in the mouth: a summary of the current evidence. AB - The importance of detecting oral malignant disease is paramount. Recent government strategies have placed an emphasis on the early detection of cancer. This paper presents a brief account of the current debate around the role of oral cancer screening and provides a summary of the results of three practice-based studies that were supported by the British Society for General Dental Surgery and the Faculty of General Dental Practice (UK). Overall, there appears to be a lack of rigour among some general dental practitioners when screening for potentially malignant disorders and their incidence in dental practice is perceived to be low. Barriers remain to the implementation of smoking-cessation schemes and many general dental practitioners feel out of their depth in tackling the abuse of alcohol, despite recognising its importance as a risk factor. Patients continue to present to their general medical practitioner (GMP) when they are concerned about something in their mouth that is not related to their teeth. GMPs' ability to manage early oral cancer is discussed. A prospective randomised controlled trial (RCT), or a demonstration study, is recommended to investigate the numbers of cases of oral cancer diagnosed in primary dental care and primary medical care and to develop standardised referral criteria for early cases of this disease to reduce under- and over-referral. The RCT could also examine the potential of using auxiliary healthcare workers and examine the impact of such a programme upon secondary care services. PMID- 20353655 TI - A study to assess the quality of information in referral letters to the orthodontic department at Kingston Hospital, Surrey. AB - AIM: To assess the quality of information included in referral letters sent to the orthodontic department at Kingston Hospital, Surrey, UK. METHODS: Referral letters sent by both general dental practitioners (GDPs) and specialist orthodontists were analysed retrospectively in order to ascertain the percentage meeting the inclusion criteria as suggested by Mossey (2006) and the British Orthodontic Society (2008) for the quality of information included in an ideal orthodontic referral letter. Thirty-five consecutive letters sent between May and September 2005 and 206 letters sent in the same period in 2008 were collected by hand and analysed against the inclusion criteria. The numbers of referral letters received from GDPs, specialist orthodontists, and others sources were also determined. RESULTS: Most of the referrals sent in 2005 and 2008 included 40-50% of the referral inclusion points. This was despite an almost twofold increase in the number of referral letters received from specialist orthodontic practitioners in 2008. The majority of the letters, from both GDPs and specialists, did not include details of the oral hygiene or caries status of the patient, or an indication of their motivation towards treatment. None of the referral letters included a plaque score. CONCLUSION: The main weaknesses in the quality of information provided in referral letters were that in more than 80% of the letters there was no mention of the patient's medical history and no comment on caries status, the standard of oral hygiene, patient motivation for treatment, or an Index of Orthodontic Treatment Need score. The quality of information included in referral letters sent to Kingston Hospital orthodontic department needs to be improved. PMID- 20353656 TI - An audit of smoking behaviours among patients attending two general dental practices in South Wales: an awareness-raising exercise for the dental team and patients. AB - AIMS: This audit aimed to quantify the number of smokers attending two general dental practices. It also aimed to establish the demographic characteristics of these smokers in terms of age, gender and deprivation status, and to raise the awareness of practice staff about smoking cessation. METHODS: Data were collected from consecutive patients (aged over 16 years) attending two general dental practices over a period of one month. The information collected included smoking status, number of cigarettes smoked, age, gender, and postcode. A deprivation score (derived from the Welsh Index of Multiple Deprivation [WIMD] for 2008) was appended to each patient record in order to provide a measure of deprivation based on the postcode of the patient. Staff at both practices were involved in the audit. Staff were given a brief pre- and post-audit questionnaire to test their knowledge on smoking cessation. The audit standard was that no more than 29% of patients should be smokers. Where relevant, data were statistically tested using the chi-square test. RESULTS: Five hundred and sixty-one patients provided data on their smoking habits. It was found that 159 (28.3%) were smokers, smoking on average 12 cigarettes per day. The average age of the sample was 46 years and 242 (43.1%) were male. Forty-eight per cent of the sample was shown to be resident in a postcode considered to be deprived. Older patients were more likely to be nonsmokers (P=0.0001). Following the final audit meeting, correct answers among staff for knowledge of the National Institute for Health and Clinical Excellence guidelines regarding effective smoking-cessation practices improved from 6% to 71%. CONCLUSION: The issue of smoking cessation has been highlighted for two dental teams. Whether the audit will result in the delivery of smoking cessation procedures within the dental practice settings cannot be established. It is clear that the desired smoking-cessation behaviours can now be contemplated by the dental teams. Further monitoring is required to establish outcomes as a result of the actions of the teams. PMID- 20353657 TI - An audit of patient referrals to the sedation department of Newcastle Dental Hospital. AB - AIM: To audit the quality of external referral communications sent to the Department of Sedation at Newcastle Dental Hospital. METHODS: A retrospective analysis was undertaken of a sample of 226 consecutive external referrals received by the sedation department of Newcastle Dental Hospital during May-July 2008. A data-collection form was used to record information provided in referrals relevant to the practice of sedation and the set standard was based on the recommendations of the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Of the 226 referrals sampled, the majority (222; 98.2%) were from general dental practitioners. Seventy-six per cent were by letter and 24% by pro forma. Although of particular relevance to sedation referrals, a medical history was provided in only 59.0% of referrals and details of previous dental treatment in only 27.5%. The use of a pro forma significantly increased the provision of information compared to a letter in the following areas: patient's telephone number, patient's medication, doctor's name and doctor's address. Significantly less information was provided in the pro forma compared to the letters concerning the name of the referring practitioner and referring practitioner's telephone number. No difference was found between letter and pro forma referrals for medical history, treatment already attempted and reason for referral. CONCLUSIONS: The findings indicate a need to improve the amount of information provided in referrals to the sedation department of Newcastle Dental Hospital in order to ensure appropriate allocation to sedation services. The quality of referrals may be improved by the distribution of referral guidelines, the use of electronic referral templates or changes to the current pro forma. PMID- 20353658 TI - Developing a mentoring culture in dentistry. Making a difference in a changing world. AB - This paper follows the recent series published in Primary Dental Care on the subject of mentoring. It is intended to place mentoring in a broader societal, professional, ethical and philosophical context. The introduction of the mentoring approach into human affairs in general, and the workplace in particular, is evidence of a fundamental shift both in the way we work together as individuals and in how we view and value ourselves as human beings. This paper reflects on the changes in thinking and attitudes in society that have led to the emergence of mentoring and coaching as elements in the approach of positive psychology. It then seeks to learn from the experience of the adoption of mentoring and coaching in other areas of work and society. It goes on to consider what impact this might have on underlying beliefs and attitudes within the profession of dentistry, and who might become the mentors and the mentees. Finally, it presents mentoring as an expression of the values and the culture of a caring profession seeking to promote the 'good life' both for its patients and for its practitioners. PMID- 20353659 TI - Automated electronic reminders to facilitate primary cardiovascular disease prevention: randomised controlled trial. AB - BACKGROUND: Primary care databases contain cardiovascular disease risk factor data, but practical tools are required to improve identification of at-risk patients. AIM: To test the effects of a system of electronic reminders (the 'e Nudge') on cardiovascular events and the adequacy of data for cardiovascular risk estimation. DESIGN OF STUDY: Randomised controlled trial. SETTING: Nineteen general practices in the West Midlands, UK. METHOD: The e-Nudge identifies four groups of patients aged over 50 years on the basis of estimated cardiovascular risk and adequacy of risk factor data in general practice computers. Screen messages highlight individuals at raised risk and prompt users to complete risk profiles where necessary. The proportion of the study population in the four groups was measured, as well as the rate of cardiovascular events in each arm after 2 years. RESULTS: Over 38 000 patients' electronic records were randomised. The intervention led to an increase in the proportion of patients with sufficient data who were identifiably at risk, with a difference of 1.94% compared to the control group (95% confidence interval [CI] = 1.38 to 2.50, P<0.001). A corresponding reduction occurred in the proportion potentially at risk but requiring further data for a risk estimation (difference = -3.68%, 95% CI = -4.53 to -2.84, P<0.001). No significant difference was observed in the incidence of cardiovascular events (rate ratio = 0.96, 95% CI = 0.85 to 1.10, P = 0.59). CONCLUSION: Automated electronic reminders using routinely collected primary care data can improve the adequacy of cardiovascular risk factor information during everyday practice and increase the visibility of the at-risk population. PMID- 20353660 TI - Long-term prescribing of antidepressants in the older population: a qualitative study. AB - BACKGROUND: High rates of long-term antidepressant prescribing have been identified in the older population. AIMS: To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. DESIGN OF STUDY: Qualitative study using in-depth semi-structured interviews. SETTING: One primary care trust in North Bradford. METHOD: Thirty-six patients aged > or =75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. RESULTS: Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. CONCLUSION: There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people. PMID- 20353661 TI - Psychotropic drug use among older people in general practice: discrepancies between opinion and practice. AB - BACKGROUND: The use of psychotropic drugs has increased over recent years in France. GPs are the first prescribers, especially for older patients. AIM: To analyse discrepancies between GPs' opinions and practice when prescribing psychotropic drugs to older patients. SETTING: Postal surveys sent to GPs all over mainland France. DESIGN OF STUDY: Cross-sectional postal study. METHOD: A questionnaire collected data on characteristics of GPs' practices, their opinions about psychotropic drug consumption in older people, and a full description of their last older patient receiving a psychotropic drug and seen last by the GP on that particular day. RESULTS: A total of 350 participating GPs saw 2498 patients aged > or =65 years. Among these patients, the prevalence of psychotropic use was 32.1% (803/2498) for anxiolytics/hypnotics, and 17.5% for antidepressants (438/2498). A total of 91% of GPs agreed that it was possible to reduce or stop psychotropic drugs for these patients. Characteristics of 339 patients taking psychotropic drug were reported: 85.8% (291/339) received at least one anxiolytic/hypnotic and 56.9% (193/339) received at least one antidepressant; there were prescribed for more than 1 year in 68.4% (199/291) and 43.5% (84/193) of the cases respectively. GPs stated that it was possible to reduce or stop anxiolytic/hypnotic drugs for only 27% (79/291) of these patients. Barriers to doing this were patients' refusal (79%), and the absence of any local offer of psychotherapy (73%) or alternative therapy (70%). CONCLUSION: A mismatch exists between GPs' intent (91%) and practice (27%) regarding reduction of psychotropic prescription in individuals aged > or =65 years. The barriers encountered should be examined further to help physicians improve management of psychotropic prescription. PMID- 20353662 TI - Euthanasia in patients dying at home in Belgium: interview study on adherence to legal safeguards. AB - BACKGROUND: Euthanasia became legal in Belgium in 2002. Physicians must adhere to legal due care requirements when performing euthanasia; for example, consulting a second physician and reporting each euthanasia case to the Federal Review Committee. AIM: To study the adherence and non-adherence of GPs to legal due care requirements for euthanasia among patients dying at home in Belgium and to explore possible reasons for non-adherence. DESIGN OF STUDY: Large scale, retrospective study. SETTING: General practice in Belgium. METHOD: A retrospective mortality study was performed in 2005-2006 using the nationwide Belgian Sentinel Network of General Practitioners. Each week GPs reported medical end-of-life decisions taken in all non-sudden deaths of patients in their practice. GP interviews were conducted for each euthanasia case occurring at home. RESULTS: Interviews were conducted for nine of the 11 identified euthanasia cases. Requirements concerning the patient's medical condition were met in all cases. Procedural requirements such as consultation of a second physician were sometimes ignored. Euthanasia cases were least often reported (n = 4) when the physician did not regard the decision as euthanasia, when only opioids were used to perform euthanasia, or when no second physician was consulted. Factors that may contribute to explaining non-adherence to the euthanasia law included: being unaware of which practices are considered to be euthanasia; insufficient knowledge of the euthanasia law; and the fact that certain procedures are deemed burdensome. CONCLUSION: Substantive legal due care requirements for euthanasia concerning the patient's request for euthanasia and medical situation were almost always met by GPs in euthanasia cases. Procedural consultation and reporting requirements were not always met. PMID- 20353663 TI - Place of death for the 'oldest old': > or =85-year-olds in the CC75C population based cohort. AB - BACKGROUND: Deaths are rising fastest among the oldest old but data on their transitions in place of care at the end of life are scarce. AIM: To examine the place of residence or care of > or =85 year-olds less than a year before death, and their place of death, and to map individual changes between the two. DESIGN OF STUDY: Population-based cohort study. SETTING: Cambridge City over-75s Cohort (CC75C) study, UK. METHOD: Retrospective analysis of prospective data from males and females aged > or =85 years at death who died within a year of taking part in any CC75C survey (n = 320); death certificate linkage. RESULTS: Only 7% changed their address in their last year of life, yet 52% died somewhere other than their usual address at the time of death. Over two-thirds were living in the community when interviewed <1 year before death, but less than one-third who had lived at home died there (less than one-fifth in sheltered housing). Care homes were the usual address of most people dying there (77% in residential homes, 87% in nursing homes) but 15% of deaths in acute hospital came from care homes. CONCLUSION: More than half the study sample of individuals of advanced old age had a change in their place of residence or care in their last year of life. These findings add weight to calls for improved end-of-life care in all settings, regardless of age, to avoid unnecessary transfers. The study data provide a baseline that can help plan and monitor initiatives to promote choice in location of care at the end of life for the very old. PMID- 20353664 TI - Challenges to advocacy in primary health care. PMID- 20353665 TI - Electronic fit notes: sickness certification in the new decade. PMID- 20353666 TI - Communicating in a crisis: the H1N1 influenza pandemic. PMID- 20353667 TI - General practice at the cutting edge of information technology, or failing to keep pace? PMID- 20353668 TI - Why do GPs prescribe psychotropic drugs when they would rather provide alternative psychological interventions? PMID- 20353669 TI - Non-cancer medications for patients with incurable cancer: time to stop and think? PMID- 20353670 TI - Working towards a 'fit note': an experimental vignette survey of GPs. AB - BACKGROUND: The Department for Work and Pensions (DWP) has designed a trial medical statement. AIM: To compare fitness for work assessment outcomes and written advice across current and trial medical statements. To examine the use of and suggestions to improve the trial medical statement. DESIGN OF STUDY: Comparative study with a two-way mixed design using questionnaire-based vignettes presenting GPs with three hypothetical sick leave cases (back pain, depression, combined back pain and depression) and medical statements (current or trial). The questionnaire also gathered GP views of using the trial Med 3. SETTING: Nine primary care organisations (PCOs) in England, Scotland, and Wales. METHOD: Five hundred and eighty-three GPs employed in PCOs in summer 2008 were randomised to receive a current or trial Med 3 postal questionnaire. GPs assessed vignette patients' fitness for work using the questionnaire medical statements. RESULTS: GPs using the trial Med 3 were less likely to advise refraining from work and more likely to provide written fitness for work advice compared to GPs using the current Med 3 form. Date sections of the trial Med 3 were used inconsistently, and a return to work date was unclear. GPs wanted further clarification of the implications of assessing a case as 'fit for some work' and its relationship to employers' willingness to follow GP advice about work. CONCLUSION: The study indicates a revised form may reduce the number of patients advised to refrain from work and increase the provision of written fitness for work information. PMID- 20353671 TI - Requests for euthanasia in general practice before and after implementation of the Dutch Euthanasia Act. AB - BACKGROUND: The Netherlands was the first country in the world to implement a Euthanasia Act in 2002. It is unknown whether legalizing euthanasia under strict conditions influences the number and nature of euthanasia requests. AIM: To investigate changes in the number of, and reasons for, requests for euthanasia in Dutch general practice after implementation of the Euthanasia Act. DESIGN OF STUDY: Retrospective dynamic cohort study comparing 5 years before (1998-2002) and 5 years after (2003-2007) implementation of the Act. METHOD: Standardised registration forms were used to collect data on requests for euthanasia via the Dutch Sentinel Practice Network. This network of 45 general practices is nationally representative by age, sex, geographic distribution, and population density. RESULTS: The mean annual incidence of requests before implementation amounted to 3.1/10,000 and thereafter to 2.8/10,000 patients. However, trends differed by sex. The number of requests by males decreased significantly from 3.7/10,000 to 2.6/10,000 (P = 0.008); the requests by females increased non significantly from 2.6/10,000 to 3.1/10,000. Before and after implementation, cancer remained the major underlying disease for requesting euthanasia: 82% versus 77% for men; 73% versus 75% for females. Pain was a major reason for a request, increasing in the period before implementation (mean 27%), but declining in the period thereafter (mean 22%). Loss of dignity became a less important reason after implementation (from 18% to 10%, P = 0.04), predominantly due to a marked decrease in the number of females citing it as a reason (from 17% to 6%, P = 0.02). CONCLUSION: There was no increase in demand for euthanasia after implementation of the Euthanasia Act. Pain as a reason for requesting euthanasia showed an increasing trend before implementation, but declined thereafter. Loss of dignity as a reason declined, especially in females. PMID- 20353672 TI - GPs' opinions on the NHS and HPA response to the first wave of the influenza A/H1N1v pandemic. AB - The first wave of influenza A/H1N1v resulted in a significant demand on primary care services. This cross-sectional study describes GPs' opinions of how information was communicated to them during this period and the overall response of the NHS and Health Protection Agency. Accessibility of current guidance and ease of obtaining antiviral medication were perceived as strengths, but clarity of the information provided was consistently perceived as poor. The majority of GPs supported the introduction of the National Pandemic Flu Service, although many raised concerns about its safety. PMID- 20353673 TI - Primary health care in Africa: do family physicians fit in? PMID- 20353674 TI - Persistent frequent attenders. PMID- 20353675 TI - Looking at the patient. PMID- 20353679 TI - Medicine and the making of interprofessional education. PMID- 20353685 TI - The response of C57BL/6J and BALB/cJ mice to increased housing density. PMID- 20353686 TI - Diversity in laboratory animal science: issues and initiatives. AB - Since diversity in the workplace began receiving scholarly attention in the late 1980s, many corporations and institutions have invested in programs to address and manage diversity. We encourage laboratory animal science to address the challenges and to build on the strengths that personal diversity brings to our field and workplaces. Diversity is already becoming increasingly relevant in the workplace and the laboratory animal science field. By addressing issues related to diversity, laboratory animal science could benefit and potentially fulfill its goals more successfully. To date, diversity has received minimal attention from the field as a whole. However, many individuals, workplaces, and institutions in industry, academia, and the uniformed services that are intimately involved with the field of laboratory animal science are actively addressing issues concerning diversity. This article describes some of these programs and activities in industry and academia. Our intention is that this article will provide useful examples of inclusion-promoting activities and prompt further initiatives to address diversity awareness and inclusion in laboratory animal science. PMID- 20353687 TI - Moving research to patient applications through commercialization: understanding and evaluating the role of intellectual property. AB - The advancement of research from discovery to the delivery of medical care can be limited without the support of industry to sponsor its continued development. Federal government financial support is generally crucial in early-stage development through funding from the NIH, National Science Foundation, and other federal agencies; however, government support generally stops shortly after basic research discoveries have been reported. Much of the cessation of financial support derives from the government's regulatory responsibilities, as sponsoring the commercialization of a product conflicts with regulation of the approval for clinical use of a drug or device. Furthermore, differences in goals, resources, and flexibility render government, as compared with private industry, inefficient and less responsive to market demands with regard to stream-lining the development of and enhancing the quality of products and services offered. Thus, industry and private investment provide the bridge that converts new discoveries into healthcare products that are available to consumers and patients. This conversion occurs through commercialization, which involves both high risks and high rewards. Taking advantage of the commercialization option for research development requires an understanding of the technology transfer process. This article reviews 5 topics: 1) industry motivation to invest in academic research; 2) institutional considerations in partnering with industry; 3) academia's interactions with inventors in the commercialization process; 4) the research institution's route to commercialization, and 5) the role of intellectual property and commercialization in the advancement of healthcare. PMID- 20353688 TI - Use of a body condition score technique to assess health status in a rat model of polycystic kidney disease. AB - Simple and noninvasive methods of assessing health and wellbeing are valuable when performing clinical evaluation of rodents used in biomedical research. Body condition score (BCS) techniques have been described for a variety of species, including mice. This method can be a sensitive objective assessment of weight loss in animal models where organ enlargement, ascites, or tumor development may mask weight loss. Although deposition of fat is similar in rats and mice, the mouse BCS technique has not been characterized in rats. Here we used the Han:SPRD rat model for polycystic kidney disease to characterize the effectiveness of the mouse BCS scale when applied to rats. This study showed a positive correlation between BCS score and renal function and a negative correlation between weight and renal function, supporting the use of BCS as an effective, noninvasive method of health assessment in this rat model. Our results also demonstrate that the BCS scale described for mice required a slight modification to capture the delay in fat deposition over the lumbar vertebrae in obese animals. PMID- 20353689 TI - Lactate and adenosine triphosphate in the extender enhance the cryosurvival of rat epididymal sperm. AB - We evaluated the cryosurvival of rat epididymal sperm preserved in raffinose modified Krebs-Ringer bicarbonate-egg yolk extender supplemented with various energy-yielding substrates (glucose, pyruvate, lactate, and ATP) and assessed the effect on sperm oxygen consumption. The incubation of sperm at 37 degrees C for 10 min in lactate-free extender decreased sperm motility and oxygen consumption before and after thawing compared with those of sperm in glucose- and pyruvate free mediums. We then focused on the effect of supplementing the extender with lactate (0, 10.79, 21.58, 32.37, and 43.16 mM) and found that sperm frozen and thawed in extender supplemented with 32.37 mM lactate exhibited the highest motility. When we supplemented extender containing 32.37 mM lactate with ATP (0, 0.92, 1.85, 3.70, and 5.55 mM), sperm frozen and thawed in the extender supplemented with 1.85 mM ATP exhibited considerably higher motility and viability than those of sperm frozen and thawed in ATP-free extender. These results provide the first evidence that supplementation of the raffinose-modified Krebs-Ringer bicarbonate-egg yolk extender with 32.37 mM lactate and 1.85 mM ATP increases of number of motile sperm before freezing and enhances the cryosurvival of rat sperm. These supplements to the extender may enhance sperm cryosurvival by improving the metabolic capacity of sperm before freezing. PMID- 20353690 TI - Extracellular ATP and dibutyryl cAMP enhance the freezability of rat epididymal sperm. AB - We studied the effects of ATP, ionomycin, and dibutyryl cAMP (dbcAMP) on the motility, freezability, and oxygen consumption of rat epididymal sperm. In vitro fertilization and intrauterine insemination were performed by using frozen-thawed rat sperm. Frozen-thawed sperm diluted in raffinose-modified Krebs-Ringer bicarbonate solution-egg yolk extender containing 1.85 mM ATP and 100 microM dbcAMP exhibited considerably higher motility and viability than sperm diluted in dbcAMP-free extender. Addition of ionomycin and dbcAMP to ATP-containing extenders did not alter the oxygen consumption rate of sperm, suggesting that extracellular ionomycin and dbcAMP are not involved in the mobilization of mitochondrial energy substrates in sperm. Further, high rates of pronucleus formation and progression to the blastocyst stage were observed in embryos produced by the fertilization of oocytes with fresh sperm in an in vitro fertilization medium supplemented with ATP and dbcAMP. Oocytes were not penetrated by frozen-thawed sperm when cocultured with cumulus-oocyte complexes in a medium without ATP and dbcAMP. In contrast, cryopreserved sperm penetrated oocytes when the gametes were cultured in an ATP- and dbcAMP-containing medium, and the resultant embryos formed blastocysts. Our results show that the dilution of rat sperm in raffinose-modified Krebs-Ringer bicarbonate solution-egg yolk extender supplemented with ATP and dbcAMP prior to sperm cryopreservation enhances the freezability of the cryopreserved sperm. Furthermore, the in vitro fertilization medium we developed effectively supports the production of embryos from both fresh and cryopreserved rat sperm. PMID- 20353691 TI - Management and care of African dormice (Graphiurus kelleni). AB - African dormice (Graphiurus spp.) are small nocturnal rodents that currently are uncommon in laboratory settings. Their use may increase as they have recently been shown to develop an infection with monkeypox virus and may prove to be a valuable animal model for infectious disease research. Because African dormice are not commercially available, an extensive breeding colony is required to produce the animals needed for research use. Husbandry modifications that increased the production of offspring were the use of a high-protein diet, increased cage enrichment, and decreased animal density. To optimize consumption of a high-protein diet, we tested the palatability of several high-protein foods in a series of preference trials. Dormice preferred wax worm larva, cottage cheese, roasted soy nuts, and canned chicken. Issues related to medical management of Graphiurus kelleni include potential complications from traumatic injury. The development of a program for the husbandry and care of African dormice at our institution typifies the experiences of many laboratory animal facilities that are asked to support the development of animal models using novel species. PMID- 20353692 TI - Disparities in ammonia, temperature, humidity, and airborne particulate matter between the micro-and macroenvironments of mice in individually ventilated caging. AB - Animal room environmental parameters typically are monitored with the assumption that the environment within the cage closely mirrors the room environment. This study evaluated that premise by examining macro- (room) and microenvironmental (cage) parameters in individually ventilated cages housing mice with variable amounts of bedding over a period of 17 d without cage changes. Intracage ammonia levels remained within recommended human guidelines but were higher than room levels, confirming that microisolation caging is efficient at preventing ammonia generated from animal waste from escaping into the room. Humidity and temperature within cages were consistently higher than room levels. Particles in the room predominantly consisted of fine particles (diameter less than 2.5 mum), presumably from the ambient atmosphere; some of these particles were found in the cage microenvironment. In addition, mouse activity within cages produced larger particles, and these particles contributed to substantially higher aerosol mass concentrations within the cage. These findings demonstrate that, although cage and room environmental parameters differ, knowledge of room environmental conditions can be used to predict certain conditions within the cage. This association is relevant in that typical animal care standard operating procedures rely on room measurements, not intracage measurements, which arguably are more important for assessing animal welfare. Further, location and ambient climate can influence particle concentrations in the room, and consequently within the animal cage, suggesting local weather patterns and air quality may account for variability among studies conducted at sites that are geographically divergent. PMID- 20353693 TI - Endotoxin, coliform, and dust levels in various types of rodent bedding. AB - Endotoxins in grain dust, household dust, and animal bedding may induce respiratory symptoms in rodents and humans. We assayed the endotoxin, coliform, and dust levels in 20 types of rodent bedding. Endotoxin concentrations were measured by using a commercial test kit, coliform counts were determined by using conventional microbiologic procedures, and dust content was evaluated by using a rotating-tapping shaker. Paper bedding types contained significantly less endotoxin than did other bedding types; the highest levels of endotoxin were detected in hardwood and corncob beddings. The range of endotoxin content for each bedding type was: corncob bedding, 1913 to 4504 endotoxin units per gram (EU/g); hardwood bedding, 3121 to 5401 EU/g; corncob-paper mixed bedding, 1586 to 2416 EU/g; and paper bedding, less than 5 to 105 EU/g. Coliform counts varied from less than 10 to 7591 cfu/g in corncob beddings, 90 to 4010 cfu/g in corncob paper mixed beddings, less than 10 to 137 cfu/g in hardwood beddings, and less than 10 cfu/g in paper beddings. Average dust content was less than 0.15% in all commercial bedding types. We conclude that paper bedding is the optimal bedding type for conducting LPS inhalation studies and that rodent bedding containing high levels of endotoxin may alter the results of respiratory and immunologic studies in rodents. PMID- 20353694 TI - Efficacy and limitations of an ATP-based monitoring system. AB - Monitoring of sanitation is an essential function of laboratory animal facilities. The purpose of the current study was to assess the ability of an ATP based system to detect microbes and organic contaminants. Serial dilutions of Escherichia coli, Staphylococcus aureus, Toxocara canis eggs, Toxoplasma gondii tachyzoites, epithelial cells, and rodent blood, urine, and feces were analyzed according to the manufacturer's recommendations. The limit of E. coli detection was 10(4) organisms; sonication of E. coli significantly improved detection, indicating incomplete bacterial lysis in the detection system. Detection of S. aureus was significantly greater than that of E. coli with a limit of detection of 10(2); sonication did not alter results. In contrast, detection of T. canis, T. gondii, RBC, and epithelial cells was robust and ranged from 2 T. canis eggs to 10 epithelial cells. Urine was weakly detected, with a limit of detection at 1:10 dilution. Detection of all cell types except epithelia had a strong linear correlation to total cell number. In addition, our data demonstrate that the efficacy of the detection system can be affected adversely by residual disinfectants and that sample-bearing swabs are stable for more than 7 h after swabbing. These data demonstrate that this ATP based system sensitively detects pure cells and organic contaminants with a strong degree of linear predictability. A limitation of the system is its inability to detect gram negative bacteria efficiently because of incomplete cell lysis. PMID- 20353695 TI - Predictors of matrilineal overthrows in large captive breeding groups of rhesus macaques (Macaca mulatta). AB - The purpose of this retrospective case-control study was to identify and assess biologically plausible variables that may predispose a captive rhesus macaque breeding colony to a matrilineal overthrow. Matrilineal overthrows are the result of members of multiple matrilines jointly attacking the highest-ranking matriline. Matrilineal overthrows in captive rhesus macaque colonies result in significant morbidity, mortality, and loss of genetic diversity. The following variables were investigated as potential determinants of overthrows: season, cage density, demographics, sex ratio, age of the alpha and beta animals, absence of the alpha and beta animals, pregnancy status of the alpha and beta females, number of adult females in the alpha matriline, recent changes in the male hierarchy, time since group formation, and number of adolescent males in the alpha matriline. Data were collected from January 1996 through January 2007. Univariate analysis indicated that absence of the alpha female from the group was associated with matrilineal overthrows, but multivariate analysis was not totally supportive. Conditional logistic regression identified number of juvenile males and number of adolescent males as associated with an overthrow; exact logistic regression was supportive. Principal component analysis followed by multivariate logistic regression identified 2 marginally nonsignificant predictors (the density and alpha factors). Our results suggest a possible association between the occurrence of a matrilineal overthrow and the following factors: absence of the alpha female, decreased housing density, number of juvenile males, and number of adolescent males. PMID- 20353696 TI - Clinical biochemistry parameters in C57BL/6J mice after blood collection from the submandibular vein and retroorbital plexus. AB - Collection of blood from the submandibular vein allows simple and rapid processing of many animals without anesthesia and facilitates rapid recovery with no signs of pain and discomfort in the mice. Here we compared the submandibular vein and retroorbital plexus blood collection methods, to determine the potential effect of the sampling technique on several clinical biochemistry parameters in C57BL/6J mice. We found statistically significant differences for 8 of the 9 biochemical parameters studied between the 2 blood sampling techniques. Compared with samples collected from the retroorbital plexus, blood obtained from the submandibular vein had higher levels of AST, ALT, protein, albumin, triglycerides, total cholesterol, and creatinine. Glucose values of retroorbital blood were higher than those from the submandibular vein. Urea levels were similar for both sampling techniques. Our results demonstrate that the technique used to obtain blood samples affects parameters commonly used to assess animal health. We recommend caution when comparing results of biochemical analysis of blood obtained from the submandibular vein in mice with reference values obtained by other blood sampling techniques. PMID- 20353697 TI - Chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques (Macaca mulatta). AB - As part of a study of antipsychotic drug treatment in monkeys, we developed a technique to provide chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques. This method allowed us to mimic the osmotic release oral delivery system currently used in humans for continuous enteral drug delivery. Rhesus macaques (n = 5) underwent gastric catheter placement by laparotomy. After the catheters were secured to the stomach, the remaining catheter length was exited through the lateral abdomen, tunneled subcutaneously along the back, and connected to a 2-mL osmotic pump enclosed in a subcutaneous pocket. Osmotic pumps were changed every 2 to 4 wk for 1 y and remained patent for the duration of the study. Four complications (including cutting of the catheter, incisional dehiscence at the pump site, and loss of 1 catheter into the abdominal cavity requiring catheter replacement) occurred among the 80 pump changes performed during the year-long study. At necropsy, histopathologic examination of the catheter implant sites revealed mild changes consistent with a foreign-body reaction. Our results indicate that the gastric catheter and osmotic pump system was well tolerated in rhesus macaques for as long as 12 mo after placement and suggest that this system will be an attractive option for use in studies that require chronic, constant-rate, gastric drug infusion in nontethered monkeys. PMID- 20353698 TI - Diagnosis of Aeromonas hydrophila, Mycobacterium species, and Batrachochytrium dendrobatidis in an African clawed frog (Xenopus laevis). AB - Here we describe diagnosis of concurrent infection with Aeromonas hydrophila, Mycobacterium spp., and Batrachochytrium dendrobatidis in a wild female Xenopus laevis captured in Chile and transported to the United States. After approximately 130 d in the laboratory, the frog was presented for dysecdysis and obtundation. After euthanasia, tissues were submitted for histopathologic evaluation and PCR analysis for B. dendrobatidis and Ranavirus. Clinically significant gross lesions included cutaneous ulcerations on the lip, right forelimb, and ventral chest. Microscopic findings included regionally extensive splenic necrosis, diffuse pneumonia, and fibrinous coelomitis all containing intralesional bacteria. PCR analysis yielded positive results for B. dendrobatidis only. Bacterial culture of the ulcerated skin and liver yielded A. hydrophila. Infection with Contracaecum spp. was diagnosed as an incidental finding. To our knowledge, this case is the first report of simultaneous infection with Aeromonas hydrophila, Mycobacterium spp., and Batrachochytrium dendrobatidis in a laboratory-maintained X. laevis captured from the wild. PMID- 20353699 TI - A naturally occurring outbreak of tuberculosis in a group of imported cynomolgus monkeys (Macaca fascicularis). AB - This case report describes the diagnosis of tuberculosis (caused primarily by Mycobacterium bovis) in a group of newly imported Chinese origin cynomolgus monkeys. We also describe the use of sedation to enhance the accuracy of evaluation of the intrapalpebral tuberculin skin test using the mammalian old tuberculin reagent and report the first known diagnosis of Mycobacterium paraffinicum in a nonhuman primate. By 48 h after injection during the second tuberculin skin test, 6 of the 80 macaques had developed eyelid reactions ranging from mild (grade 1) to severe (grade 4). Given the range and severity of reactions, we suspected an outbreak of tuberculosis in the group. Because of the nature of the reactions, we sedated the animals at the 72-h evaluation to more closely observe and then palpate the injected eyelid. Evaluation of unsedated animals revealed 22 with a reaction to mammalian old tuberculin. We confirmed these 22 cases and identified an additional 11 animals with reactions when the monkeys were sedated. Mycobacterial culture of tissue from 6 macaques with reactions confirmed M. bovis in 3 animals. In addition, 1 of these 3 animals was culture-positive for both M. bovis and M. paraffinicum, and another was culture positive for M. avium complex only. The addition of sedation to facilitate visual inspection and then palpation of the injected eyelid of these macaques increased the accuracy of evaluation and understanding of the number and severity of reactions to tuberculin skin testing. PMID- 20353700 TI - Uterine leiomyoma in a Guyanese squirrel monkey (Saimiri sciureus sciureus). AB - An adult female squirrel monkey (Saimiri sciureus) presented with a 3.0 x 2.5 cm firm mass palpable within the caudal abdomen. Differentiation of the organs or structures involved with the mass could not be achieved with radiography or ultrasonography. Exploratory laparotomy revealed a mass within the lumen of the uterus; the mass was removed by partial hysterectomy. On gross examination, the mass was a focally extensive, unencapsulated, firm, solitary tumor. Histologic examination revealed that the mass was composed of interlacing bundles of smooth muscle cells with little fibrous stroma. The cells were elongated with poorly delineated borders and cigar-shaped nuclei, each containing a single, small nucleolus. Fewer than 1 mitosis per 20 high-power (magnification, x 400) fields were present. These gross and histologic findings supported a diagnosis of uterine leiomyoma. Although leiomyomas are the most common tumor of the reproductive tract in nonhuman primates, to our knowledge the current lesion is the first uterine leiomyoma reported to occur in a squirrel monkey. PMID- 20353701 TI - Prevalence and management of pain, by race and dementia among nursing home residents: United States, 2004. AB - KEY FINDINGS: Data from the National Nursing Home Survey, 2004. About one-quarter of all nursing home residents reported or showed signs of pain. Nonwhite residents and residents with dementia were less likely to report or show signs of pain compared with white residents and residents without dementia. Nonwhite residents with dementia were least likely, and white residents without dementia were most likely to report or show signs of pain. Forty-four percent of nursing home residents with pain received neither standing orders for pain medication nor special services for pain management (i.e., appropriate pain management). Among residents with dementia and pain, nonwhite residents were more likely than white residents to lack appropriate pain management. PMID- 20353702 TI - [Gastric carcinoma and chronic gastritis: epigenetic regulation of CDH1 (E Cadherin), CDKN2A (p16INK4A), PTGS2 (COX-2) and EGFR genes through methylation]. AB - The genetic and epigenetic alterations are being studied as one of the causes of gastric cancer (GC) progression and development. DNA methylation is an epigenetic alteration which leads to suppressor gene silencing and proto-oncogene activation, playing an important role in carcinogenesis. The histological types of gastric carcinoma have different genetic paths and the knowledge of the molecular bases of tumoral progression leads to diagnostic accuracy and attempted therapy. CDH1 (E-cadherin) and CDKN2A (p16(INK4A)) genes are thought to be tumoral suppressor genes and PTGS2 (COX-2) and genes are involved in tumour regulation and growth. In one hand, gene silencing as an epigenetic phenomenon, and in the other hand, gene expression enhancement due to possible demethylation, simultaneously, can facilitate carcinogenesis and tumoral progression. Our aim was to relate CDH1, p16(INK4A), COX-2 and EGFR genes DNA methylation with the several histological types of gastric carcinoma and chronic gastritis. We studied 55 formalin fixed paraffin embedded gastric biopsies: 35 were GC specimens (12 diffuse type, 15 intestinal type and 8 indeterminate type, according to Lauren's classification) and 20 samples had chronic gastritis (CG). The DNA was treated with sodium bisulfite after extraction and then performed Methylation Specific PCR (MSP). Statistical analysis was based on chi-square test and Exact Fisher's test. CpG island methylation was detected in 94% of the GC samples for CDH1, 91% for COX-2, 80% for p16(INK4A) and no methylation was detected in EGFR gene (0%). In CG, CpG island methylation was found in 100% for CDH1 and COX-2 genes, 90% for p16(INK4A) and 20% for EGFR. These results reveal significant differences in EGFR gene methylation distinguishing GC from CG (p < 0, 01), suggesting that gene demethylation leads to malignant transformation and favours the use of tyrosine kinase inhibitors in its treatment. Genes COX2 e p16INK4A lower methylation in intestinal and diffuse types of GC, favours their different role in respective histogenesis. PMID- 20353703 TI - [Risk factors for Parkinson disease: an epidemiologic study]. AB - The etiology of Parkinson's disease (PD) remains in a certain part unknown. Both genetic susceptibility and environmental factors are sometimes considered to be putative contributors to its origin. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging, once pure genetic forms of PD are rare. The purpose of this study was to investigate possible environmental and familial risk factors for PD. We performed a hospital based case-control study using 88 PD patients with neurologist confirmed diagnostic, and 176 sex, age, and residence similar controls. Several possible risk factors were evaluated related to life style, past history, family history, occupational history and other exposures to potential neurotoxin agents. Statistical differences, using a 95% confidence interval, were observed in positive family history of PD (p = 0,002), occupation category (p = 0,001), rural living (p = 0,037), living/working near a industry (p = 0,017), exposure to pesticides, herbicides and in-secticides (p < 0,001), coffee consumption (p = 0,036) and tea consumption (p = 0,001). Sex and age adjusted logistic regression showed as potential risk factors, a positive family history of PD (odds ratio [OR] = 9,996; 95% confidence interval [CI] = 2,19-45,597), blue collar occupations (OR = 3,967; 95% CI = 1,670-9,426), exposure to pesticides, herbicides and insecticides (OR = 2,619 ; 95% CI = 1,170-5,862). An inverse relationship was found between tea consumption and the risk of PD (OR = 0,356; 95% CI = 0,174-0,727). The results of the study show that both familial and environmental factors may contribute to the development of PD. Like other studies suggest, PD is of unknown, but presumably multifactorial etiology. PMID- 20353705 TI - [Spider poisoning in Portugal: fact or myth?]. AB - There are 800 known species of spiders in Portugal. Of these, only two may cause any kind of medical condition: the Mediterranean black-widow (Latrodectus tredecimguttatus) and the violin spider (Loxosceles rufescens). Both are relatively common in the country, the latter inclusively in urban areas. It is frequent in Portugal for some types of necrotic lesion to be attributed to spider bites. However, as in the rest of the world, evidences are often circumstantial. Most probably, some of the reported cases may in fact represent misdiagnoses of serious conditions such as infections by Streptococcus group A or Methicillin resistant Staphylococcus aureus. The correct diagnosis of spider poisoning must always be submitted to the following steps: (1) confirmation or observation of the biting, with verification of medical signs compatible with it; (2) the spider should be captured immediately or right after the bite, dead or alive; (3) identification of the spider by a taxonomist. It is extremely important that the medical community does not associate any necrotic lesion with a spider bite based on merely circumstantial evidence. Doing it is to neglect the real cause of such condition and to delay the effective cure. In reality, given their rarity, spider bite lesions should be relegated to the end of the differential diagnostic list of necrotic skin lesions. PMID- 20353704 TI - [The impact caused by the insertion of family members in the treatment of the adult social phobic patient]. AB - INTRODUCTION: Although several clinical studies on adult social phobic patients have been developed of late, related literature fails to present studies of interventionist nature dealing with family participation in the patient's treatment. OBJECTIVE: The present article is intended to verify the impact caused by the insertion of family members in the treatment of the adult social phobic patient. METHOD: Subjects included 15 male and 15 female patients affected by social phobia, age range 25 to 40 years, and showing depressed mood; eight caregivers were also included in the study. Instruments used for the study comprised the SCID, SAD, and FNE scales. Family members answered to the adapted Burden Interview scale. Three therapy groups were formed and each one included ten patients that attended 20 weekly 90-minutes sessions. Caregivers' attendance was fortnightly carried out with ten one-hour sessions. Data were analyzed using the paired Student's t test and the adopted significance level was 5%. RESULTS: Twelve patients were able to conclude the program; ten participants quit the ongoing program; eight patients were present at the initial interview only. After the intervention, nine participants showed SAD and FNE decreased scores; two patients showed decreased FNE scores only; and increased scores in both scales were observed in one patient. All the participants who had family members included in the program concluded the intervention. Statistical analysis showed significant mean differences between SAD and FNE scales after the procedure. CONCLUSION: The present study showed that social phobic patients adherence to treatment is likely to increase when family members also participate in the intervention. PMID- 20353706 TI - [General practice and family medicine vocational training: the specialty internship doctor's profile, in Portugal]. AB - AIM: To characterize a vocational training doctor's population that chooses General Practice and Family Medicine as career, in Portugal, trying to identify a profile; to know the proportion of the trainees that choose this specialty as a first-line option, for their professional future; to analyze the relationship between that choice and the sociodemographic and professional characteristics of the General Practice and Family Medicine trainees. TYPE OF STUDY: Observational and cross-sectional study, with an analytic component. POPULATION: Doctors who entered the vocational training program for General Practice and Family Medicine in Portugal, during the year of 2005 (N = 228). METHODS: Postal questionnaire survey of all doctors that began vocational training during the year of 2005. Descriptive statistics were calculated and we use the ?2 and T test to analyze the relationship between the variables (a = 0,05). RESULTS: The overall response was 47,81% (n = 109). The profile found is mostly feminine (76, 15%), average age = 30, 2 years (DP = 6,28), Portuguese nationality (79,82%), graduate less than five years (Mo = 2002), and with a professional work average in medicine = 3,0 years (DP = 3,87). Most of trainees has no experience, working in undifferentiated Primary Care settings (87,04%). The specialty was chosen as a first-line option by 78,90% of the trainees, regardless of their profile. CONCLUSION: The high proportion of trainees choosing this specialty, as a first line option, is a relevant result in this study. Identifying the specialty internship Doctor's profile, through a representative population, gives us an important evidence for future investigations, in a moment of a primary care reform in Portugal. PMID- 20353707 TI - [Attachment style in patients with systemic lupus erythematosus]. AB - PURPOSE: The aim of this study is to characterize patients with SLE in terms of attachment style, personality, psychopathological morbidity and quality of life, comparing them with a healthy volunteer group. METHOD: We collected 53 patients diagnosed with SLE, in a specialized consultation of autoimmune diseases. The patients were characterized clinically (by means of SLICC/ACR, SLEDAI, length of disease and therapy) and psychologically at the same time. The psychological evaluation was made by the application of self-measured questionnaires, namely AAS, BSI, HADS, SF-36, EMBU and NEO-FFI, and also by the completion of a psychological interview. RESULTS: SLE patients adopted, mostly, an anxious, insecure attachment style. We found high levels of somatisation and psychopathological morbidity, particularly depression. We also observed an impairment of the quality of life in these patients. We found statistically significant and positive correlations between the insecure attachment styles and psychopathological morbidity, we also noticed negative associations with the dimensions of quality of life. By means of multiple linear regression models, some clinical variables (SLEDAI and SLICC/ACR) highlight as predictors of insecure attachment styles. CONCLUSION: SLE has specific and particular characteristics that lead to insecure attachment styles, psychopathological morbidity and impairment of quality of life. Thus arises the need for a specific and complementary psychotherapeutic intervention, adapted to the needs of these patients. PMID- 20353708 TI - [Laboratorial diagnosis of Cushing's syndrome]. AB - Cushing's syndrome is a diagnostic challenging endocrinous entity. Many laboratorial examinations are available for the study of these patients. Available examinations are not absolutely trustworthy for its diagnosis, so that, very often, it is necessary to conjugate informations from different laboratory tests. In this revision one exposes the current evidence and the suggestions of different authors in the laboratorial diagnosis of Cushing's syndrome and the differential diagnosis in patients with biochemical confirmed diagnosis. PMID- 20353709 TI - [Antihypertensive treatment in pregnancy]. AB - Pregnancy hypertensive disorders represent a frequent gestational pathology. It is one of the most important causes of maternal demise and perinatal morbidity/mortality in the world. Antihypertensive treatment is part of a vast therapeutic arsenal used for prevention of severe complications. However, data from literature research have been controversial about benefits of antihypertensive treatment. We performed a literature review about antihypertensive treatment in severe pre-eclampsia, describing drugs' pharmacological particularities and scientific evidences about their efficacy and safety. It is not controversial that treatment of hypertensive emergency must be instituted. The ideal medication used in those cases is not defined, therefore the real benefits of maintenance antihypertensive treatment in pre-eclampsia remains unclear. PMID- 20353710 TI - [Current knowledge on major complications after whole brain radiotherapy or radiosurgery]. AB - Brain radiotherapy aims at controlling the pathological lesion(s) as well as avoiding damaging critical structures. However, side effects may occur. Neurocognitive function is often involved impairing quality of life. This dysfunction is among the most frequent complications of brain irradiation. Sparing as much as feasible hippocampus and/or other critical structures like the motor unit might reduce neurocognitive dysfunction, motor disturbance and other complications occurring after whole brain radiotherapy or radiosurgery. PMID- 20353711 TI - [Management of vertigo]. AB - INTRODUCTION: Dizziness is a non specific and incapacitating symptom. Its classification is based on the patient complaints and categorized in pre-syncope, disequilibrium, lightheadness and vertigo. Vertigo is the most prevalent cause of dizziness. This article pretends to review the management of vertigo, its causes, differential diagnosis and treatment. METHODS: The articles used in this review were obtained from a Medline search with the keywords vertigo and dizziness, from publications from the past 5 years in the English, Spanish and Portuguese languages. DISCUSSION: Vertigo is the most prevalent cause of dizziness in primary care. It is caused by an asymmetric involvement in the basal activity of the central and peripheric vestibular pathways. It occurs in episodes and the intensity of this symptom diminishes as the causative factor dissipates or compensation occurs. The clinical evaluation is bases on the clinical history and physical examination. The first step in the differential diagnosis is to differentiate central vertigo from peripheral vertigo. Knowing the duration of symptoms, precipitating factors and associated symptoms and performing the Dix Hallpike manoeuvre is important in achieving this. The treatment of vertigo must be specific and oriented to the cause, and the use of symptomatic therapy must be reserved to the acute episodes. The definite treatment are rehabilitation exercises. PMID- 20353712 TI - [The association between self-rated health and health care utilization in retired]. AB - OBJECTIVE: This article attests the association between self-rated health and health care utilization in a retired population by a narrative review. METHOD: A systematic review was carried out from 1967 to 2007 to identify studies on self rated health, in the databases MEDLINE, LILACS e SCIELO. The OVID software was used to Medline research. Contacts with experts were used. The key words retirement, self-rated health, health care utilization and narrative review were used in Portuguese, Spanish and English versions. Al the abstracts were analyzed, but only trials that associated self-rated health in retirement and health care utilization were fully analyzed. RESULTS: Thirty one out of 443 abstracts were selected to be fully analyzed. Current data indicates that health deterioration, poor self-rated health and increased health care utilization are associated with early retirement, due to disability, but not with individuals who worked until retirement by age. CONCLUSION: Retirement is probably associated with increased public expenses and increased health care utilization in retired with a poor self rated health. PMID- 20353713 TI - [Recurrent hypercortisolism after removal of an ACTH secretor pituitary adenoma associated with an adrenal macronodule]. AB - A 29 years old patient was sent to our Outpatient Clinic of Endocrinology presenting clinic of hypercortisolism. Laboratorial study: High urinary free cortisol (UFC); serum cortisol - 25 microg/dl (8 am) (5-25) and 20 microg/dL (11pm); ACTH - 20 pg/mL (9-52) (8 am) and 14 pg/mL (11 pm); serum cortisol after dexamethasone suppression test: 14,9 mg/dL; CRH test: elevation of ACTH; Pituitary MRI: microadenoma; abdominal CT: nodule on the left adrenal. During inferior petrosal sinus sampling with CRH stimulation, ACTH reached 368 pg/mL on the right and 136 pg/mL on the left side. The patient was submitted to transsphenoidal surgery. After surgery, hypertension and physical stigmata improved. In 2006, a relapse of Cushing syndrome was suspected due to worsening of hypertension and increase of weight. A slight increase of UFC, undetectable ACTH and serum cortisol after dexamethasone suppression test equal to 16 microg/dL were found. On abdominal CT, the adrenal nodule kept the same characteristics. In December 2006, the patient was submitted to left adrenalectomy. After surgery, blood pressure normalized, UFC and serum cortisol were reduced, needing substitutive therapy. Progressive tapering of hydrocortisone doses lead to discontinuation in March 2007. He is clinically well, without any treatment. This is an unusual case, in which after surgical cure of Cushing disease, secretory autonomy of a coexisting adrenal nodule occurred. This clinical case is relevant, pointing out the complexity of hypercortisolism cases and the need of long follow-up. PMID- 20353714 TI - [A rare case of hyperandrogenism: bilateral Leydig cell tumor of the ovary]. AB - BACKGROUND: The androgen-secreting tumors constitute fewer than 1% of ovarian tumors. Leydig cell tumor is one of the most common of this type of lesion and it is usually benign, small and unilateral. CASE REPORT: A 67 year old woman was referred to the Endocrine clinic due to hirsutism (score 22 Ferriman-Gallwey) and male type alopecia with 3 years of evolution and progressive worsening. Biochemically she had high levels of serum testosterone - 662 ng/dl (N < 62 ng/dl). Transvaginal ultrasonography and abdomen-pelvic CT scan didn't show any signs of adrenal or ovarian tumors. Bilateral oophorectomy was performed and histopathologic exam revealed bilateral Leydig cell tumors, measuring 1cm each. Four months after surgery, the patient had a marked improvement of the signs (score 3 Ferriman-Gallwey) and normalized testosterone levels (35.9 ng/dl). DISCUSSION: Androgen-secreting tumors are rare, but they should be excluded in cases of rapid onset of virilization and elevated androgen levels. Tumors are frequently undetectable by imaging techniques because of their small dimensions, exploratory surgery by a skilled team is frequently necessary and is often the best treatment for the majority of these cases. In this case report we present a rare case of bilateral Leydig cell tumor. Only five cases have been reported in the literature.The clinical history and the elevated levels of testosterone had suggested the presence of an androgen-producing tumor, despite the difficulty of the diagnosis on imaging techniques. Due to the fact that our patient was in a post-menopausal stage, we decided that the appropriate treatment would be bilateral oophorectomy. The histopathologic disclosed the diagnosis and allowed the patient's cure. PMID- 20353715 TI - [Bladder stones in acute spinal cord injury]. AB - Urologic complications are an important cause of morbidity and even mortality in patients with spinal cord injury (SCI). It has been estimated that within eight years after injury, approximately 7% of SCI patients would develop kidney stones, whereas 36% would have bladder stones. Risk factors for urolithiasis among patients with SCI include complete spinal cord injury, lesions at or above the 4th thoracic spinal cord segment, upper motor neurone type of bladder, urinary tract infection with urease producing bacteria, recurrent urinary tract infection, indwelling catheters, presence of residual urine and immobilization. Detection and removal of bladder stones are important to prevent possible complications such as recurrent urinary tract infection, urosepsis and renal failure. The authors describe a clinical case of a patient with acute SCI that developed bladder stones and discuss its possible causes. PMID- 20353716 TI - [Medicine in ancient Mesopotamia - part 2]. AB - The second part embraces exclusively the main characteristics of the medicine in Ancient Mesopotamia, in its main facets: concept of disease, healers and practice. The disease was considered a divine punishment or resultant from a malign influence. Insofar, the medicine began by being preventive, by the use of appropriate amulets or by offerings or sacrifices intending to pacify those malign forces. The treatment of the generality of the diseases privileged the expulsion of those spirits and malign influences from the patient body, purifying it, which was done by the specific intervention of a approximately shipu (clergymanexorcist); not having results, the treatment was continued by the asu (practical healer) that appealed to a group of physical manipulations, limited surgical acts and the administration or application of prescriptions, resultants of the mixture of organic and inorganic substances. In case of failing, the patients (as well as common healthy individuals or rule leaders) could fall back upon a priest diviner (baru) that, by examination of the organs of an animal especially sacrificed for, would give a final decision about the disease or the future. Besides this more occult facet, nourished in religious faiths and in the magic, the medicine of Ancient Mesopotamia included rational knowledge, certainly as the result of systematic patients observation and semiotic interpretation. From those observations and knowledge referred to the Sumerian period, carefully logged, refined and transmitted to the following generations, it was built a valuable group of texts with the description of symptoms, signs, diagnosis and prognostic of the most common diseases, still identifiable in the present. PMID- 20353717 TI - [Breach of confidentiality in medicine]. AB - This paper deals with the historical development of the legal protection of medical confidentiality in Portugal. Situations that have lead to its relativization, and the present Portuguese legal framework (Criminal Code and the Code of Professional Ethics of the Ordem dos Medicos) are analysed. Finally, the paper focuses on the implementation of the legal framework, taking into account the specific situation of HIV/AIDS. PMID- 20353718 TI - Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis. AB - The present study was conducted to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cyclophosphamide (CP)-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. Forty-eight healthy adult male Sprague-Dawley rats were divided into six groups of eight rats each. The control group was treated with placebo; the LC, EA and CP groups were given LC (10 mg kg(-1)), EA (2 mg kg(-1)) and CP (15 mg kg(-1)), respectively, alone; the CP+LC group was treated with a combination of CP (15 mg kg(-1)) and LC (10 mg kg(-1)); and the CP+EA group was treated with a combination of CP (15 mg kg(-1)) and EA (2 mg kg(-1)). All treatments were maintained for 8 weeks. At the end of the treatment period, bodyweight and the weight of the reproductive organs, sperm concentration and motility, testicular tissue lipid peroxidation, anti-oxidant enzyme activity and apoptosis (i.e. Bax and Bcl-2 proteins) were determined. Administration of CP resulted in significant decreases in epididymal sperm concentration and motility and significant increases in malondialdehyde levels. Although CP significantly increased the number of Bax-positive (apoptotic) cells, it had no effect on the number of Bcl-2 positive (anti-apoptotic) cells compared with the control group. However, combined treatment of rats with LC or EA in addition to CP prevented the development of CP-induced lipid peroxidation and sperm and testicular damage. In conclusion, CP-induced lipid peroxidation leads to structural and functional damage, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protect against the development of these detrimental effects. PMID- 20353719 TI - Developmental potential of bovine oocytes following IVM in the presence of glutathione ethyl ester. AB - Glutathione (GSH) is synthesised during oocyte maturation and represents the oocyte's main non-enzymatic defence against oxidative stress. Inadequate defence against oxidative stress may be related to poor embryo quality and viability. In the present study, bovine oocytes were matured in vitro in the presence of GSH ethyl ester (GSH-OEt), a cell permeable GSH donor, and its effects on subsequent fertilisation and embryo development were assessed. GSH-OEt significantly increased the GSH content of IVM oocytes without affecting fertilisation or Day 3 cleavage rates. Maturation in the presence of GSH-OEt did not significantly increase the blastocyst rate compared with control oocytes. However, 5 mM GSH-OEt treatment resulted in significantly higher blastocyst total cell number. The GSH level of IVM oocytes was significantly decreased in the absence of cumulus cells and when cumulus-oocyte complexes were cultured in the presence of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. The addition of GSH-OEt to cumulus-denuded or BSO-treated oocytes increased the GSH content of bovine oocytes and restored the rate of normal fertilisation, but not embryo development, to levels seen in control oocytes. Thus, GSH-OEt represents a novel approach for effective in vitro elevation of bovine oocyte GSH and improvement in blastocyst cell number. PMID- 20353720 TI - Seminal plasma proteins do not consistently improve fertility after cervical insemination of ewes with non-sorted or sex-sorted frozen-thawed ram spermatozoa. AB - The effect of supplementation of sex-sorted and non-sorted spermatozoa with seminal plasma protein (SPP) on fertility after cervical insemination was examined in the present study. Spermatozoa were sorted into high purity X and Y chromosome-bearing spermatozoa or not sorted and then either supplemented with SPP (>10 kDa) before freezing and/or after thawing (non-sorted only) or processed without supplementation. Inseminations were performed over 2 days with ewes receiving 100 or 25 million motile non-sorted spermatozoa in the cervix or uterus, respectively, or two cervical inseminations of 3.5 million motile sorted spermatozoa. Pregnancy rates in cervically inseminated ewes were unaffected by supplementation of sorted or non-sorted spermatozoa with SPP before freezing compared with no supplementation. The effect of post-thaw supplementation of non sorted spermatozoa with SPP on pregnancy rates after cervical insemination varied with the day of insemination (P < 0.05); fertility was similar to laparoscopic insemination on Day 1 (56.0 +/- 10.2% v. 58.6 +/- 10.1%), but not on Day 2 (23.1 +/- 7.4% v. 66.7 +/- 9.2%). In conclusion, under the conditions of the present study, SPP did not consistently improve pregnancy rates after cervical insemination with frozen-thawed ram spermatozoa. This is the first report of pregnancies (5/56 ewes inseminated) after cervical insemination with frozen thawed sex-sorted ram spermatozoa. Although the success rate is low, the findings are encouraging because ewes inseminated with the sex-sorted spermatozoa received only 7% of the recommended dose (100 million motile) for cervical insemination of frozen-thawed spermatozoa. PMID- 20353722 TI - Characterisation of bovine epiblast-derived outgrowth colonies. AB - The aim of the present study was to characterise bovine epiblast-derived outgrowth colonies (OCs) with respect to the embryonic origin of their cellular components. Epiblasts were isolated mechanically from bovine Day 12 embryos. Epiblasts were cultured on feeder layers of SNL cells (neomycin-resistant leukaemia inhibitory factor (LIF)-producing STO cells) in Dulbecco's modified Eagle's medium (DMEM)/F12 medium supplemented with 15% fetal calf serum, 5% KnockOut Serum Replacement, LIF, basic fibroblast growth factor, non-essential amino acids (NEAA) and nucleosides. Samples were fixed on Days 4, 6 and 8 of culture and processed for immunocytochemistry and transmission electron microscopy. Epiblasts formed OCs consisting of a central core of epiblast-like cells with a basal plate of flattened cells extending outwards from the core. The cells of the core showed nuclear octamer-binding transcription factor 4 (OCT4) staining, indicating an epiblast origin, and some also stained positive for cytoplasmic vimentin. Adjacent cells were linked by tight junctions towards the surface of the colony and rested on a basal lamina. The cells of the basal plate predominantly stained for alpha1-fetoprotein (AFP), indicative of a possible hypoblast origin. Only a few cells scattered within the basal plate exhibited cytokeratin 8 staining, indicating a trophectoderm nature. The intensity of OCT4 and vimentin staining within the core had decreased by Day 8 of culture. In conclusion, OCs derived from bovine Day 12 epiblasts display a central core of OCT4-stained cells of a potential epiblast origin surrounded by a basal plate of mainly AFP-stained cells of a potential hypoblast nature. PMID- 20353721 TI - Abnormalities in the transcription of reprogramming genes related to global epigenetic events of cloned endangered felid embryos. AB - The present study examined transcription levels of the Oct4, DNMT1, DNMT3a, DNMT3b, HAT1 and HDAC1 genes in cloned felid embryos developing from single one cell to blastocyst stages. IVF, cloned domestic and leopard cat embryos had low Oct4 and HAT1 levels during the early stages, but transcript expression increased at the eight-cell and blastocyst stages. In contrast, expression in the cloned marble cat embryos was low at all stages. Transcription patterns of HDAC1 were altered in cloned embryos compared with IVF embryos. Transcription levels of DNMT1 decreased markedly throughout development of both IVF and cloned embryos. In IVF embryos, DNMT3a transcripts rarely appeared in the four- to eight-cell stages, but levels increased in the morula to blastocyst stages. In contrast, in cloned embryos, DNMT3a transcript levels were high at the one- to two-cell stages, decreased during subsequent cell division and then increased again at the blastocyst stage. The IVF and cloned embryos showed similar DNMT3b transcription patterns, starting with low levels at the two-cell to morula stages and reaching a maximum at the blastocyst stage. These results suggest that the low level of Oct4 transcripts may be responsible, in part, for the failure of blastocyst production in the cloned marbled cat. However, higher transcription of the DNA methylation genes and lower transcription of the histone acetylation genes were observed in cloned compared with IVF embryos, suggesting that the felids' donor nucleus could not completely reprogramme the nuclear genome and so the re establishment of embryonic totipotency was not achieved. PMID- 20353723 TI - Ago2 and GW182 expression in mouse preimplantation embryos: a link between microRNA biogenesis and GW182 protein synthesis. AB - MicroRNA-mediated RNA interference appears to play a role in early development and differentiation processes in preimplantation embryos. However, the expression of its key effectors, including Ago2, a key component of the RNA-induced silencing complex, and GW182, a critical component of GW bodies (GWBs), has not been assessed in preimplantation embryos. To characterise the roles of Ago2 and GW182 in early embryo development, we determined their transcription and protein synthesis in mouse embryos. Transcript levels of Ago2 and GW182 increased steadily from the one-cell stage through to the blastocyst stage when data were not normalised against an internal reference. However, when normalised against the internal standard, transcript levels for both genes were highest in four-cell stage embryos and decreased steadily through to the blastocyst stage. Indirect immunocytochemistry showed that both AGO2 and GW182 proteins were expressed in each stage in the early embryo and were observed to colocalise in the morula and blastocyst stages. Specific silencing of mRNA expression by short interference (si) RNA against Ago2 or Dicer1 decreased the expression of selected apoptosis- and development-related microRNAs, but did not inhibit development up to the blastocyst stage. However, transcription levels of Oct3/4, Nanog and Sox2 were decreased in both Ago2- and Dicer1-knockdown embryos at the blastocyst stage. Furthermore, although knockdown of these genes did not change transcript levels of GW182, GW182 protein synthesis was decreased in blastocyst stage embryos. These results suggest that Ago2 and Dicer1 regulate GW182 protein expression in mouse embryos, which is linked to microRNA biogenesis and likely to be important for differentiation in the blastocyst stage. PMID- 20353724 TI - Detection of condensin I and II in maturing pig oocytes. AB - The multiprotein complexes known as condensins (I and II) are major players in chromosome dynamics in mitotic and meiotic cells. Here, we report for the first time the detection of different condensin subunits from both complexes in mammalian oocytes. Using immunoblotting analysis we examined expression levels of condensin subunits during meiotic maturation of porcine oocytes. The expression of the core subunit structural maintenance of chromosomes 2 (SMC2), identical in both condensin complexes, did not change significantly during maturation. Similarly, there was no significant change in the expression of the chromosome associated protein (CAP)-H and CAP-H2 subunits, components of condensin I and II, respectively. Conversely, the expression profiles of CAP-G, CAP-D2 (condensin I) and CAP-D3 (condensin II) were more interesting. At least two isoforms of the CAP D2 subunit were detected, along with three isoforms of the CAP-D3 and CAP-G subunits. We suggest that this diverse migration of subunit isoforms is due to post-translational modification. Earlier, it was reported that non-SMC proteins are phosphorylated by cyclin-dependent kinase 1. In the present study, we analysed the phosphorylation status of the three subunits in oocyte extracts using alkaline phosphatase treatment and we found that at least the fastest migrating form of CAP-D3 was likely to be phosphorylated in maturing porcine oocytes. In addition, the localisation of CAP-H and CAP-H2 subunits was examined using immunofluorescence staining with specific antibodies, as well as following microinjection of their enhanced green fluorescent protein-tagged mRNA into germinal vesicle-stage oocytes. CAP-H was found in the cytoplasm, whereas CAP-H2 was localised within the nucleus. PMID- 20353725 TI - Preservation of beluga (Delphinapterus leucas) spermatozoa using a trehalose based cryodiluent and directional freezing technology. AB - A beluga (Delphinapterus leucas) sperm preservation method was developed for use in genome banking and AI. In Study 1, glycerol-based cryodiluents (modified BF5F and modified Platz Diluent Variant (PDV)) were unable to maintain adequate progressive motility using straws (fast and slow freezing rate (FR)) or pellets (slow FR). Neither freezing method nor FR affected in vitro sperm characteristics (P > 0.05), but retention of prefreeze progressive motility following thawing was greater (P < 0.05) for BF5F (21%) than PDV (15%). In Study 2, examining the effects of straw freeze-thawing using BF5F with glycerol (1 and 3%, v/v) or trehalose (46 and 91 mM) on sperm characteristics, samples cryopreserved in trehalose exhibited superior (P < 0.05) in vitro parameters compared with their glycerol-treated counterparts. In Study 3, compared with a straw method, directional freezing using 91 mM trehalose enhanced (P < 0.05) sperm characteristics, with samples retaining 38%, 75% and 61% of their prefreeze progressive motility, curvilinear velocity and viability, respectively. A higher (P < 0.05) proportion of motile spermatozoa displayed rapid velocity after directional (21 +/- 1%) compared with straw (12 +/- 3%) freezing. Systematic development of a cryodiluent and the use of directional freezing resulted in beluga spermatozoa exhibiting adequate post-thaw quality for genome banking and use in AI. PMID- 20353726 TI - Numb regulates meiotic spindle organisation in mouse oocytes. AB - Numb is an adaptor protein that controls the fate of cells in different species through asymmetrical inheritance by sibling cells during division. It has been investigated extensively in mitosis, mostly in neural progenitor cells, but its function in meiosis remains unknown. The present study was designed to investigate the expression, subcellular localisation and functional roles of Numb during mouse oocyte meiotic maturation. Using real-time polymerase chain reaction and western blotting, we found that the expression of Numb increased from the germinal vesicle (GV) to MII stages. Immunofluorescent staining revealed that Numb was mainly concentrated in the GV before meiosis resumption, aggregated in the vicinity of the chromosomes after GV breakdown and then localised to the spindle poles from prometaphase I to MII. Nocodazole treatment resulted in spindle destruction and Numb diffusion into the cytoplasm. However, Numb appeared at the spindle poles again once the spindles had formed when nocodazole-treated oocytes were washed and cultured for spindle recovery. Depletion of Numb by RNA interference resulted in chromosome misalignment, spindle deformation and even doubled spindle formation. Our results suggest that Numb is critical for spindle organisation during mouse oocytes meiosis. The present study provides evidence of a new function for Numb in addition to its action as a cell fate-determining factor. PMID- 20353727 TI - Xenografting restores spermatogenesis to cryptorchid testicular tissue but does not rescue the phenotype of idiopathic testicular degeneration in the horse (Equus caballus). AB - Spermatogenesis from many mammalian species occurs in fragments of normal testis tissue xenografted to mice. Here we apply xenografting to the study of testicular pathology. Using the horse model, we investigated whether exposure to a permissive extratesticular environment in the mouse host would rescue spermatogenesis in cryptorchid testicular tissue or in tissue affected by idiopathic testicular degeneration (ITD). In cryptorchid tissue, where the extratesticular environment is abnormal, xenografting induced spermatogenesis up to meiosis in a subpopulation of seminiferous tubules. Thus, spermatogonia survive and partially retain their potential to differentiate in cryptorchid horse testes. In contrast, the primary defect in equine ITD is hypothesised to be tissue autologous. In support of this, xenografting did not restore spermatogenesis to tissue affected by ITD, thus confirming that the testis itself is primarily diseased. This outcome was not affected by supplementation of exogenous gonadotropins to the mouse host or by reconstitution of a normal reproductive regulatory axis supplied by functional porcine testicular xenografts. These studies demonstrate the usefulness of xenografting for the study of testicular pathology. PMID- 20353728 TI - Effects of changes in the concentration of systemic progesterone on ions, amino acids and energy substrates in cattle oviduct and uterine fluid and blood. AB - Early embryo loss is a major factor affecting the conception rate in cattle. Up to 40% of cattle embryos die within 3 weeks of fertilisation while they are nutritionally dependent on oviduct and uterine fluids for their survival. Inadequate systemic progesterone is one of the factors contributing to this loss. We have characterised the effects of changes in systemic progesterone on amino acid, ion and energy substrate composition of oviduct and uterine fluids on Days 3 and 6, respectively, of the oestrus cycle in cattle. Oviduct and uterine fluids were collected in situ following infusion of progesterone. There was no effect of progesterone on oviduct fluid secretion rate; however, uterine fluid secretion rate was lowered. Progesterone increased uterine glucose, decreased oviduct sulfate and, to a lesser degree, oviduct sodium, but had no effect on any of the ions in the uterus. The most marked effect of progesterone was on oviducal amino acid concentrations, with a twofold increase in glycine, whereas in the uterus only valine was increased. These results provide novel information on the maternal environment of the early cattle embryo and provide further evidence of progesterone regulation of oviduct amino acid concentrations in cattle. PMID- 20353729 TI - Seasonal reproduction in wild and captive male koala (Phascolarctos cinereus) populations in south-east Queensland. AB - The effects of breeding season (late spring to early autumn) on south-east Queensland male koala fertility were examined to improve the efficacy of the AI procedure and to determine the practicality of using free-range animals as semen donors for a genome resource bank. Seasonal changes in male koala reproductive function were assessed in a wild free-range population (n = 14; obtained every 6 weeks from January to November 2005), a necropsied healthy wild population (n = 84; obtained monthly from September 2004 to August 2005) and a captive population (n = 7; obtained monthly from October 2005 to October 2006). Reproductive parameters investigated included bodyweight, coat score, sternal gland area and activity, testosterone secretion, reproductive anatomy volume and semen quality (before and after cryopreservation). Collectively, these findings show that reproduction in male koalas from south-east Queensland changes seasonally and that winter appears to be the optimal season in which to collect semen samples by electroejaculation. While it was possible to repeatedly collect semen from free range koalas for future genetic management via potential storage in a genome resource bank, the survival of these spermatozoa after cryopreservation was poor and will require further improvement. PMID- 20353730 TI - Evaluation of the function of fresh and frozen-thawed sex-sorted and non-sorted stallion spermatozoa using a heterologous oocyte binding assay. AB - The aim of the present study was to evaluate the potential oocyte binding ability and functional integrity of fresh or frozen-thawed, sex-sorted or non-sorted stallion spermatozoa. In the absence of effective IVF procedures in the horse, a heterologous sperm-binding assay was used as an indicator of fertilising capacity to assess differences in the ability of stallion spermatozoa to bind to bovine oocytes. The functional integrity of four treatment groups was assessed: (1) fresh non-sorted spermatozoa; (2) fresh sex-sorted spermatozoa; (3) frozen-thawed non-sorted spermatozoa; and (4) frozen-thawed sex-sorted spermatozoa. Spermatozoa found in association with the zona pellucida of the bovine oocytes were deemed 'attached' or 'bound' depending on their characterisation as either acrosome intact or acrosome reacted, respectively. Significantly less frozen-thawed spermatozoa were found attached to the oocytes compared with fresh spermatozoa. No significant differences were identified between the number of attached sex sorted and non-sorted frozen-thawed spermatozoa. However, significantly more sex sorted than non-sorted fresh spermatozoa were found attached to the oocytes after 1 h coincubation, although after 3 h coincubation this difference was no longer apparent. In conclusion, sex-sorted fresh and frozen-thawed stallion spermatozoa are functionally capable of attaching and binding to bovine oocytes in vitro. Furthermore, fresh sex-sorted spermatozoa attach better than non-sorted spermatozoa, suggesting that they have a more advanced capacitation-like status. PMID- 20353731 TI - Spatiotemporal expression of alpha(1), alpha(3) and beta(1) integrin subunits is altered in rat myometrium during pregnancy and labour. AB - Integrins are transmembrane extracellular matrix (ECM) receptors composed of alpha- and beta-subunits. Integrins can cluster to form focal adhesions and, because there is significant ECM remodelling and focal adhesion turnover in the rat myometrium during late pregnancy, we hypothesised that the expression of alpha(1), alpha(3) and beta(1) integrin subunits in the rat myometrium would be altered at this time to accommodate these processes. Expression of alpha(1) and beta(1) integrin subunit mRNA was significantly increased on Days 6-23 of pregnancy compared with non-pregnant (NP) and postpartum (PP) time points (P < 0.05). In contrast, alpha(3) integrin subunit mRNA expression was significantly increased on Days 14, 21 and 22 compared with NP, Day 10, 1 day PP and 4 days PP (P < 0.05). A relative gene expression study revealed that, of the integrins studied, the expression of beta(1) integrin mRNA was highest in pregnant rat myometrium. The alpha(1), alpha(3) and beta(1) integrin subunit proteins became immunolocalised to myocyte membranes in situ by late pregnancy and labour in both myometrial muscle layers. Increased alpha(1), alpha(3) and beta(1) integrin gene expression during gestation and the specific detection of these subunits in myocyte membranes during late pregnancy and labour may contribute to the cell-ECM interactions required for the development of a mechanical syncytium. PMID- 20353732 TI - Laboratory and imaging features of kidney involvement in autoimmune pancreatitis: incidence, correlation, and steroid therapy response. AB - AIM: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis. AIP has been suggested to be complicated by tubulointerstitial nephritis or glomerulonephritis, implying that the kidney is involved as a phenotype of IgG4 positive multi-organ lymphoproliferative syndrome; however, the clinical significance of this novel entity is not well-defined. METHODS: We conducted a retrospective cohort analysis of 47 (male, 39; female, 8) AIP patients. RESULTS: The patients (mean age, 70.3 +/- 9.5 years) had a mean observation period of 4.1 years. Before treatment, renal dysfunction with an eGFR of 30 and 15 ml/min/1.73 m2 developed only in 10.6% (5/47) and 2.1% (1/47) of the patients, respectively. Nevertheless, urinary N-acetyl-beta-D-glucosaminidase and alpha1-microglobulin levels were elevated in 78.6% (11/14) and 30.8% (4/13) of the patients, respectively. Renal involvement in contrast-enhanced CT imaging was present in 18.2% (8/44) of the patients and was associated with proteinuria (p = 0.04) and a decrease in eGFR (p < 0.01). Furthermore, a follow-up CT study (mean, 545 days) revealed improved kidney lesions in 80.0% (4/5) of the patients after oral corticosteroid administration. In contrast, first-time kidney involvements appeared newly in 3.6% (1/28) of the patients after steroid therapy for nonrenal AIP symptoms, and in 14.3% (1/7) of the patients under no specific therapy (p = 0.02). CONCLUSION: Although severe renal failure develops rarely in AIP patients, renal abnormalities have been significantly detected by biochemical and radiological tests. Oral corticosteroid administration, even when not targeting symptomatic nephropathy, can treat and prevent kidney involvements in AIP. PMID- 20353733 TI - Referral patterns of primary care physicians for chronic kidney disease in general population and geriatric patients. AB - BACKGROUND: Late referral of patients with chronic kidney disease (CKD) by primary care physicians (PCPs) is associated with poor outcomes. We sought to assess factors influencing PCPs referral patterns in the general population and in geriatric patients, and compared their perceptions to the referral patterns. METHODS: We retrospectively reviewed 268 patients with Stage 3 CKD (early referral) and 280 with Stage 4 CKD (appropriate referral) seen in renal clinic and compared them to 268 randomly selected non-referred Stage 4 CKD patients from primary care physicians office records. We also surveyed 400 regional PCPs on factors influencing their referral for CKD. RESULTS: Non-referred patients were significantly (p < 0.05) more likely to be over 65 years (OR: 3.5; 95% CI: 2.3 - 5.2), females (OR: 1.4; 95% CI: 1.0 - 2.0) and of non-white race (OR: 2.6; 95% CI: 1.5 - 4.5) after adjusting for relevant confounding variables. Charlson comorbidity index greater than 4 was associated with non-referral when the non referral group was compared to the early referral group. Among geriatric patients, women and a higher comorbidity index were associated with non-referral. 25% of PCPs completed the survey and 62% PCPs were unfamiliar with K/DOQI referral guidelines. Age > 75 years, limited life expectancy, patient noncompliance or refusal to consider dialysis influenced PCPs decision to refer. CONCLUSIONS: Our study shows that elderly women, minorities and patients with multiple comorbidities are at risk for non-referral for CKD care. Educating PCPs on the appropriate referral of CKD patients, especially those at risk for late or non-referral to a nephrologist is warranted, as are trials assessing different educational strategies. PMID- 20353734 TI - Outcomes associated with serum phosphorus level in males with non-dialysis dependent chronic kidney disease. AB - BACKGROUND/AIMS: Hyperphosphatemia is associated with higher mortality and increased incidence of end-stage renal disease in patients with non-dialysis dependent CKD (NDD-CKD), but there has not been a concomitant assessment of mortality and progressive kidney disease that would also account for cumulative effects of hyperphosphatemia. METHODS: In order to account for the cumulative effects of abnormal serum phosphorus we examined associations of not only baseline, but also time-averaged serum phosphorus levels with all-cause mortality, the composite of mortality or ESRD and the slopes of estimated glomerular filtration rate (eGFR), by using Cox models and mixed effects models in a contemporary cohort of 713 males with moderate and advanced NDD-CKD. RESULTS: Higher baseline and time-averaged serum phosphorus were both associated with mortality and with the composite outcome. A 1 mg/dl higher time-averaged serum phosphorus was associated with a multivariable adjusted hazard ratio of all cause mortality (95% CI) of 1.56 (1.19 - 2.05), p = 0.001. Higher serum phosphorus was associated with a steeper slope of eGFR in unadjusted analyses, but this association became non-significant after multivariable adjustments. CONCLUSION: The cumulative burden of hyperphosphatemia is associated with increased mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if lowering serum phosphorus can result in improved mortality in this population. PMID- 20353735 TI - Treatment of vitamin D deficiency in CKD patients with ergocalciferol: are current K/DOQI treatment guidelines adequate? AB - BACKGROUND: Vitamin D deficiency/insufficiency (VDDI) is common in CKD patients and may be associated with abnormal mineral metabolism. It is not clear whether the K/DOQI recommended doses of ergocalciferol are adequate for correction of VDDI and hyperparathyroidism. METHODS: Retrospective study of 88 patients with CKD Stages 1 - 5 and baseline 25-hydroxyvitamin D level < 30 ng/ml (< 75 nmol/l). Patients treated with ergocalciferol as recommended by K/DOQI guidelines. Only 53 patients had elevated baseline PTH level for the CKD stage. Patients were excluded if they received vitamin D preparations other than ergocalciferol or phosphate binders. 25-hydroxyvitamin D level, intact PTH level (iPTH), and other parameters of mineral metabolism were measured at baseline and after completion of ergocalciferol course. RESULTS: 88 patients with CKD were treated with ergocalciferol. Mean age 56.8 +/- 9.5 years and 41% were males. The mean (+/- SD) GFR was 28.3 +/- 16.6 ml/min. At the end of the 6-month period of ergocalciferol treatment, the mean 25-hydroxyvitamin D level increased from 15.1 +/- 5.8 to 23.3 +/- 11.8 ng/ml (37.75 +/- 14.5 to 58.25 +/- 29.5 nmol/l) (p < 0.001). Treatment led to > or = 5 ng/ml (12.5 nmol/l) increases in 25-hydroxyvitamin D level in 54% of treated patients, and only 25% achieved levels > or = 30 ng/ml (75 nmol/l). Mean iPTH level decreased from 157.9 +/- 125.9 to 150.7 +/- 127.5 pg/ml (p = 0.5). Only 26% of patients had > or = 30% decrease in their iPTH level after treatment with ergocalciferol. CONCLUSIONS: Current K/DOQI guidelines are inadequate for correcting VDDI or secondary hyperparathyroidism in CKD patients. Future studies should examine the effects of higher or more frequent dosing of ergocalciferol on these clinical endpoints. PMID- 20353736 TI - The higher risk of death on peritoneal dialysis in the United States is not explained by background general population mortality: the CANUSA study revisited. AB - The CANUSA investigators reported a near doubling of the risk of death in peritoneal dialysis patients treated at U.S. sites compared to Canadian centers. Recently, evidence has suggested that background mortality rates in the general population might be responsible for differences in death rates on dialysis. The objective of this study was to determine if differences in background mortality in the general population were responsible for the increased risk of death observed in American patients in the CANUSA study. The CANUSA study was a prospective cohort study of 680 consecutive peritoneal dialysis patients at 14 centers in the U.S. and Canada. Extensive baseline data were available for all patients. The expected mortality rate of an individual of the same age, sex, and country of residence was determined at the time of enrollment in the CANUSA study. Cox proportional hazards models were used to determine if background mortality rates were responsible for the observed differences in survival between the two countries. Background mortality rate in the general population was associated with an increased risk of death on peritoneal dialysis, but after adjustment for other baseline factors, it was no longer significant. The adjusted, relative hazard of dying in the U.S. compared to Canada was unchanged after further adjusting for background mortality rate in statistical models (HR = 1.93; 95% confidence interval: 1.13 - 3.28). In conclusion, the increased risk of mortality in U.S. patients enrolled in the CANUSA study was not explained by differences in the background mortality rate in the general population. PMID- 20353737 TI - Pain prevalence in patients with chronic kidney disease. AB - BACKGROUND: The prevalence of pain in patients with chronic kidney diseases (CKD) is not known. In the current study, we aim to determine the prevalence of pain in CKD patients and its associations with various medical and psychosocial factors. METHODS: Consecutive CKD patients who were presented to the renal clinic at Olive View-UCLA Medical Center, a Los Angeles County tertiary referral center, over a 3 month period were interviewed on their medical and psychosocial histories and a history of pain including duration, severity and source. Chi2-testing for independence and binary logistic regression performed for the presence of pain and CKD stages as well as other medical and psychosocial factors were determined. A separate survey for pain was also done for 100 consecutive non-CKD patients who were presented to our ambulatory medicine clinic for routine care. RESULTS: 54.6% of 130 patients with known CKD interviewed were women. Any type of pain of at least a 2 week duration was reported in 72.9%. The most common source of pain was musculoskeletal. The presence of pain of less than a 2 week duration was associated with worse CKD stages (3 - 5 versus 1 - 2) and non-exercisers. Higher body mass index was associated with having pain lasting longer than a 2 week duration. Among patients who had pain, 33.8% used acetaminophen, 15.4% nonsteroidal anti-inflammatory drugs and 7.8% combination analgesics. In contrast to CKD patients, only 9% of non-CKD patients reported to have any type or duration of pain. CONCLUSIONS: Pain was much more prevalent among our CKD compared with non-CKD patients. PMID- 20353738 TI - Body fluid volume and nutritional status in hemodialysis: vector bioelectric impedance analysis. AB - BACKGROUND: Protein-energy malnutrition and hypervolemia are major causes of morbidity and mortality in patients on chronic hemodialysis (CHD). The methods used to evaluate nutritional status and volume status remain controversial. Vector bioelectric impedance analysis (vector- BIA) has recently been developed to assess both nutritional status and tissue hydration. The purpose of the study was to assess the nutritional status and volume status of patients on CHD with conventional nutritional assessment methods and with vector-BIA and then to compare the resulting findings. METHODS: 76 Mexican patients on CHD were studied. Nutritional status and body composition were assessed with anthropometry, biochemical variables, and the modified Bilbrey nutritional index (mBNI), the results were compared with both conventional BIA and vector-BIA. RESULTS: The BNI was used to determine the number of patients with normal nutritional status (n = 27, 35.5%), and mild (n = 31, 40.8%), moderate (n = 10, 13.2%) and severe malnutrition (n = 8, 10.5%). Patients displayed shorter vectors with smaller phase angles or with an overhydration vectorial pattern before the initiation of their hemodialysis session. There was general improvement to normal hydration status post-dialysis (p < 0.05); however, 28% remained overhydrated as assessed by vector-BIA. The vector-BIA results showed that worse malnutrition status was associated with greater volume overload (p < 0.05). Diabetes mellitus (DM) was associated with shorter vectors with smaller phase angles (a vectorial pattern of overhydration and cachexia) (p < 0.05). Patients with lower serum creatinine presented with shorter vectors and smaller phase angles (vectorial patterns of malnutrition and/or overhydration) (p < 0.05). In women, lower serum albumin (< 3.4 g/dl) correlated with greater overhydration and malnutrition (p < 0.05). CONCLUSIONS: In this population, the vector-BIA showed that 28% of the population remained overhydrated after their hemodialysis session. Diabetics and those with moderate or severe malnutrition were more overhydrated, which is a condition that may be associated with increased cardiovascular morbidity. Because nutritional and volume status are important factors associated with morbidity and mortality in CHD patients, we focused on optimizing the use of existing methods. Our studies suggest that vector-BIA offers a comprehensive and reliable reproducible means of assessing both volume and masses at the bedside and can complement the traditional methods. PMID- 20353739 TI - Brucellosis in dialysis patients. Does it exist? AB - BACKGROUND: Brucellosis is a zoonotic disease transmittable to humans. It is diagnosed either by isolation of Brucella organism in culture of blood or other sample types (e.g., bone marrow or liver biopsy specimens), or by a combination of serological tests and clinical findings. Dialysis patients constitute a special population group with an impaired autoimmune system and a propensity to develop infections, such as brucellosis. This paper presents the high incidence of brucellosis in our dialysis patients during last year, while there was not any zoonotic infection recorded in the previous at least 5 year period. METHODS RESULTS: This is a retrospective study including 8 dialysis patients, undergoing renal replacement therapies (5 patients were on hemodialysis (HD) and 3 on peritoneal dialysis (PD)), who out of a total of 124 patients developed brucellosis, during the last year. Four patients were male and four female and their mean age was 67 +/- 9 years. Clinical presentation of Brucellosis infection was mild with low-grade fever and symptoms of influenza. All patients were living in places where animal brucellosis was prevalent. Infection was diagnosed on the basis of clinical symptoms and signs and with polymerase chain reaction (PCR) analysis of peripheral blood. The affected patients had consumed fresh unpasteurized milk and cheese and were treated with oral doxycycline and oral rifampicin for 6 weeks. All patients are in follow up for at least 1 year, during which there were no relapses. CONCLUSIONS: Brucellosis is a zoonotic disease that can occur in dialysis patients who are susceptible to infection under certain conditions. Our brucellosis patients lived in agricultural and veterinary areas and had consumed unpasteurized milk and cheese and insufficiently cooked meat derived from infected animals. PMID- 20353740 TI - Uterine leiomyoma causing urinary obstruction of the transplanted kidney. AB - Obstruction of the ureter as a cause of acute or chronic kidney injury in the transplanted kidney is unusual beyond the perioperative period. We present a case of ureteric obstruction, infection and septicemia caused by a large uterine leiomyoma in a patient 8 years post transplantation. Initial treatment comprised of intravenous fluid and antibiotics followed by urgent drainage of the collecting system. Subsequent hysterectomy resolved the obstruction with resolution of renal failure. In young female kidney transplant recipients, gynecologic causes, although rare, need to be considered as possible etiologies of urinary obstruction and renal dysfunction. PMID- 20353741 TI - Polyarthritis and anemia in a hemodialysis patient: systemic lupus erythematosus following treatment with interferon alpha. AB - Autoimmune manifestations may occur with interferon alpha (IFNalpha) therapy. However IFNalpha-induced systemic lupus erythematosus is a rare event. We report a 33-year-old hemodialysis patient who presented polyarthritis and anemia 4 months after initiation of IFNalpha for chronic hepatitis C. Systemic lupus erythematosus was diagnosed. Clinical symptoms improved rapidly with interruption of the treatment and a low-dose steroid therapy. This is the first case of IFN induced SLE in a hemodialysis patient to confirm the major role of IFNalpha in the lupus physiopathology. Treatment with steroid therapy does not seem to worsen the HCV infection. PMID- 20353742 TI - Acute lymphoblastic leukemia complicated by acute renal failure: a case report and review of the literature. AB - The patient, a previously healthy woman, presenting with acute renal failure and anemia, was admitted to our hospital. Her serum creatinine (Scr) had increased from 0.79 - 2.69 mg/dl over three days and hemoglobin had decreased from 12.1 - 7.8 g/dl over 4 weeks. Mild compression fracture and degeneration of the lumbar vertebra and skull were observed in X-ray. The renal biopsy showed acute proximal tubular lesions induced by multiple calcium deposition. A bone marrow biopsy showed that primitive lymphocyte was up to 92.5%. After making a diagnosis of acute lymphoblastic leukemia complicated with acute kidney injury induced by hypercalcemia, CRRT (continued renal replacement therapy) and chemotherapy were used immediately. Ten days later, the blood calcium had gradually decreased from 3.88 to normal range (1.8 mmol/l) and the renal function was back to normal (Scr 0.93 mg/dl). This unusual case shows that a patient who has a syndrome of acute renal failure, electrolyte disturbances, anemia, and elevated LDH needs bone marrow puncture to eliminate renal injury caused by hematologic diseases. PMID- 20353743 TI - Therapeutic implications of heparin-induced thrombocytopenia complicating acute hemodialysis. AB - Although patients undergoing acute hemodialysis (HD) constitute a group at risk for heparin-induced thrombocytopenia (HIT), the optimal therapeutic strategy remains undefined. We describe a case of HIT complicated with right subclavian vein thrombosis in a patient with chronic renal insufficiency undergoing acute HD for oligoanuria and pulmonary edema. Circulating anti-heparin-PF4 complex antibodies were detected. Past medical history was relevant for an otherwise unexplained self-limited episode of thrombocytopenia following acute HD one year earlier after an anterior STEMI. All sources of heparin were discontinued and alternative anticoagulation was initiated with argatroban, a direct-thrombin inhibitor with hepatic clearance, followed by transition to warfarin. Prevention of tunneled HD catheter obstruction was accomplished with low-dose alteplase catheter locking solution. No bleeding occurred with argatroban anticoagulation. Platelet count recovered and no further thrombotic complications were observed. The present report illustrates the diagnostic and therapeutic challenges of HIT complicating acute HD. PMID- 20353744 TI - Impairment of renal function in a patient with IgA deficiency-associated mesangioproliferative glomerulonephritis. PMID- 20353745 TI - Teicoplanin pharmacokinetics in critically ill patients on continuous veno-venous hemofiltration. AB - Pharmacokinetics of teicoplanin (TP) was assessed in critically ill patients on continuous veno-venous hemofiltration (CVVH), in eleven patients, after the first dose and in another four after repeated administration. The TP peak concentration amounted to 55.44 +/- 15.90 microg/ml and 81.28 +/- 28.55 microg/ml (mean +/- SD), the trough concentration 6.4 +/- 1.7 microg/ml and 21.3 +/- 5.0 microg/ml, the half-life 15.7 +/- 5.7 and 35.1 +/- 12.3 h, the apparent volume of distribution 0.84 +/- 0.22 and 0.48 +/- 0.09 l/kg and the TP clearance 39 +/- 12 and 11 +/- 4 ml/h/kg after the first dose and after repeated administration, respectively. The mean sieving coefficient of TP was 0.15. After a 1,200 mg loading dose, daily maintenance doses of 600 - 1,800 mg were required for achieving trough levels of 15 - 25 microg/ml. Therapeutic drug monitoring is indispensable during CVVH because of a considerable variability of TP pharmacokinetics. PMID- 20353746 TI - In-vitro and in-vivo characteristics of a modified-release double-pulse formulation for a water soluble drug. AB - OBJECTIVE: The aim of the present study was to evaluate the in-vitro dissolution and in-vivo pharmacokinetic profile of a novel two-phase modified-release formulation for diltiazem hydrochloride, as a water-soluble drug. MATERIALS AND METHODS: The delivery system consisted of two tablets inserted into a capsule. Both tablets comprised a coated drug core-matrix. The coating of the first tablet was intended to produce a first phase with a relatively fast release profile, while that of the second tablet included a unique controlling membrane designed to achieve a delayed controlled-release profile. Three different formulations were tested for their dissolution profiles both in water media and in buffer with a pH of 6.8. These formulations were also evaluated for their pharmacokinetic profile in healthy volunteers after single administration of a 240 mg dose. Serial venous blood samples were collected over 36 h post administration to measure diltiazem levels by HPLC. In addition the in-vivo /in-vitro correlation (IVIVC) was calculated for these formulations. RESULTS: The in-vitro characteristics of these formulations demonstrated a controlled release profile in both media but with different characteristics, as in Formulation 3 where faster dissolution profile obtained in water but slower one in pH 6.8 buffer. In vivo the pharmacokinetic profile of these formulations showed that arabinogalactan containing formulations achieved plasma levels which allow a once daily administration. IVIVC calculation demonstrated that dissolution tested in buffer 6.8 media better correlates with the percent absorbed in-vivo and the best results were achieved with the formulation containing the highest amount of polysaccharide in the coating. CONCLUSION: It is concluded that the developed formulations achieved a controlled release profile both in-vitro and in-vivo which are suitable for once-daily administration. PMID- 20353747 TI - Pharmacokinetics and the antiplatelet effect of a new clopidogrel formulation, clopidogrel besylate, in healthy subjects. AB - BACKGROUND: Clopidogrel, a thienopyridine derivative, is an inhibitor of platelet aggregation induced by adenosine diphosphate (ADP). We compared the pharmacokinetics and the antiplatelet effect of two clopidogrel formulations (clopidogrel besylate (test) and clopidogrel bisulfate (reference)). SUBJECTS AND METHODS: The study was conducted in 40 healthy subjects in a randomized, open label, 2-period crossover manner. Each subject received a single loading dose of 150 mg clopidogrel on Day 1 followed by a daily dose of 75 mg clopidogrel from Day 2 to Day 7. After the first dose blood samples for pharmacokinetic analysis of clopidogrel and SR26334 were collected over 24 h. The pharmacodynamic variables, i.e., the inhibition of ADP-induced platelet aggregation, were measured over 264 h. RESULTS: No serious adverse events occurred during the study period. The mean plasma concentration-time profiles of clopidogrel and SR26334 for the two formulations were comparable. The 90% confidence intervals (CIs) for the log-transformed ratios for pharmacokinetic parameters (Cmax and AUC) of SR26334 fell within the predefined pharmacokinetic equivalence range of 80 - 125%. However, the upper limits of 90% CI of Cmax and AUC for clopidogrel exceeded the equivalence range. The two formulations showed similar antiplatelet profiles. The 90% CIs of DeltaEmax and DeltaAUEC of platelet aggregation inhibition fell within the equivalence range of 80 - 125%. CONCLUSION: Both clopidogrel formulations were well-tolerated. The study population showed no serious AEs. The test formulation proved pharmacokinetically non-inferior to the reference formulation. The test formulation showed an antiplatelet effect on ADP induced platelet aggregation similar to the reference formulation. The two formulations were considered pharmacodynamically equivalent in terms of platelet aggregation inhibition. PMID- 20353748 TI - Change of psychotropic drug prescription for schizophrenia in a psychiatric institution in Beijing, China between 1999 and 2008. AB - BACKGROUND: To date, no study has investigated how prescription patterns change over time in Chinese patients with schizophrenia. This study aimed to determine psychotropic drug prescription patterns and the use of electroconvulsive therapy (ECT) for schizophrenia and their changes over time in a large psychiatric institution in Beijing, China. METHODS: The case notes of inpatients with schizophrenia were scrutinized to identify psychotropic drug prescription patterns and the use of ECT on November 10, 1999 and the same calendar day in 2008 and to compare the two surveys. RESULTS: In 1999, 45.1% of inpatients with schizophrenia were on first-generation antipsychotic drugs (FGA), while 52.9% were on second-generation antipsychotic drugs (SGA). In 2008, the percentage of patients on FGAs decreased to 15.1%, while those on SGAs increased to 77.2%. The proportion of schizophrenia patients on mood stabilizers and antidepressants rose from 3.3% and 4.3% in 1999 to 18% and 9.5% by 2008, respectively. Use of ECT grew from 0.5% in 1999 to 5.6% by 2008. The proportion of schizophrenia patients not prescribed antipsychotic drugs changed from 5.6% in 1999 to 13.7% in 2008. CONCLUSIONS: The prescription pattern of psychotropic drugs changes considerably over time, even in the same clinical setting. Mental health professionals need to keep up with changes in the prescription patterns of psychotropic drugs in order to serve their patients at the best possible level. The socio-economic reasons for not prescribing antipsychotic drugs to schizophrenia patients should be further explored. PMID- 20353749 TI - High thiopurine metabolite concentrations associated with lymphopenia in inflammatory bowel disease (IBD) pediatric patients receiving aminosalicylates combined with azathioprine. AB - OBJECTIVE: Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients. MATERIALS AND METHODS: Data from 71 patients treated for at least 1 y by azathioprine and aminosalicylates were recorded. 6-TGN and 6-MeMPN concentrations, blood cell counts and liver function tests were compared between patients taking and those not taking aminosalicylates. RESULTS: Aminosalicylate therapy was associated with a significant increase in mean 6-TGN but also 6-MeMPN concentrations. In patients in remission, 6-TGN level was related to aminosalicylate dosage (r = 0.561, p = 0.010). Lymphopenia rate was higher in patients receiving combined therapy compared to monotherapy whereas a slight rise in leucopenia was found. CONCLUSIONS: This observation suggests that the higher frequency of lymphopenia may be associated with the elevated 6-TGN concentrations recovered in patients treated with aminosalicylates. This combination does not improve remission rate but could increase adverse effects especially lymphopenia. PMID- 20353750 TI - Protopanaxatriol metabolites identified by LC-MS/MS after oral administration in mice. AB - OBJECTIVE: 20(S)-Protopanaxatriol (Ppt), a well-known end metabolite of protopanaxatriol-type saponins, has recently been reported to have the same bioactivity as its prototype. Whether or not Ppt could be further metabolized into other compounds in vivo is still unknown. The present study is aimed to determine the structures of Ppt metabolites in mice. MATERIALS: The metabolites were produced by intragastric gavage of Ppt in mice. The homogenate of small intestine was used for analysis after solid phase extraction. METHODS: The metabolic profile of Ppt was investigated by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which were also used to identify the structures of metabolites. Accurate mass measurement using LC-time of flight MS was applied to determine the element composition of metabolites and thus to confirm their proposed structures. RESULTS: One Phase I and three Phase II metabolites were detected at 1 h, 5 h, and 10 h after administration of Ppt, which were the same at the three time points. The Phase I metabolic changes observed included dehydrogenation and hydroxylation of the steroid-like structure, as well as formation of an ester bond at C-20 of the side chain. The Phase II metabolites involved conjugation to aminoethylsulfonic acid after hydrolysis of the ester bond. A possible biotransformation pathway was proposed. CONCLUSIONS: Ppt yielded four metabolites in vivo, and 1 h was enough to complete the biotransformation process of Ppt. PMID- 20353751 TI - Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: a single dose, randomized, open-label, two-way crossover study. AB - BACKGROUND AND AIMS: Leflunomide is a disease-modifying antirheumatic drug (DMARD) with comparable efficacy to methotrexate in the treatment of rheumatoid arthritis. We compared the pharmacokinetic characteristics of two leflunomide formulations in healthy subjects and assessed whether these formulations were bioequivalent. SUBJECTS AND METHODS: A randomized, two-way, crossover study was conducted in 24 healthy male volunteers to compare the pharmacokinetics of two leflunomide formulations after administration of a single 20 mg dose of each drug with a 7 week washout period. Blood samples for the analysis of A77 1726, the main active metabolite of leflunomide, were obtained 624 h after drug administration. RESULTS: After administering a single dose of 20 mg of each leflunomide formulation, the mean AUC(0-t) and Cmax values of A771726 were 487.3 +/- 167.6 microg*h/ml and 2.24 +/- 0.85 microg/ml for the reference formulation and 468.5 +/- 148.6 microg*h/ml and 1.98 +/- 0.45 microg/ml for the test formulation, respectively. The 90% confidence intervals of the test/reference mean ratios for AUC(0-t), AUC(0-inf), and Cmax fell within the predetermined equivalence range of 0.8 - 1.25. No serious adverse events occurred during the study period. CONCLUSIONS: The two leflunomide formulations showed similar pharmacokinetic profiles in terms of A77 1726, and the test formulation was found to be bioequivalent to the reference formulation with respect to the rate and extent of leflunomide absorption. PMID- 20353752 TI - The specificity of frutalin lectin using biomembrane models. AB - Frutalin is a homotetrameric alpha-d-galactose (d-Gal)-binding lectin that activates natural killer cells in vitro and promotes leukocyte migration in vivo. Because lectins are potent lymphocyte stimulators, understanding the interactions that occur between them and cell surfaces can help to the action mechanisms involved in this process. In this paper, we present a detailed investigation of the interactions of frutalin with phospho- and glycolipids using Langmuir monolayers as biomembrane models. The results confirm the specificity of frutalin for d-Gal attached to a biomembrane. Adsorption of frutalin was more efficient for the galactose polar head lipids, in contrast to the one for sulfated galactose, in which a lag time is observed, indicating a rearrangement of the monolayer to incorporate the protein. Regarding ganglioside GM1 monolayers, lower quantities of the protein were adsorbed, probably due to the farther apart position of d-galactose from the interface. Binary mixtures containing galactocerebroside revealed small domains formed at high lipid packing in the presence of frutalin, suggesting that lectin induces the clusterization and the forming of domains in vitro, which may be a form of receptor internalization. This is the first experimental evidence of such lectin effect, and it may be useful to understand the mechanism of action of lectins at the molecular level. PMID- 20353753 TI - Na+-Ca2+ exchanger contributes to Ca2+ extrusion in ATP-stimulated endothelium of intact rat aorta. AB - The role of Na(+)-Ca(2+) exchanger (NCX) in vascular endothelium is still matter of debate. Depending on both the endothelial cell (EC) type and the extracellular ligand, NCX has been shown to operate in either the forward (Ca(2+) out)- or the reverse (Ca(2+) in)-mode. In particular, acetylcholine (Ach) has been shown to promote Ca(2+) inflow in the intact endothelium of excised rat aorta. Herein, we assessed the involvement of NCX into the Ca(2+) signals elicited by ATP in such preparation. Removal of extracellular Na(+) (0Na(+)) causes the NCX to switch into the reverse-mode and induced an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), which disappeared in the absence of extracellular Ca(2+), and in the presence of benzamil, which blocks both modes of NCX, and KB-R 7943, a selective inhibitor of the reverse-mode. ATP induced a transient Ca(2+) signal, whose decay was significantly prolonged by 0Na(+), benzamil, DCB, and monensin while it was unaffected by KB-R 7943. Notably, lowering extracellular Na(+) concentration increased the sensibility to lower doses of ATP. These date suggest that, unlike Ach-stimulated ECs, NCX promotes Ca(2+) extrusion when the stimulus is provided by ATP in intact endothelium of rat aorta. These data show that, within the same preparation, NCX operates in both modes, depending on the chemical nature of the extracellular stimulus. PMID- 20353754 TI - The fate of the internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with beta-arrestin. AB - Internalization of the apelin receptor by apelin-13 is characterized by dissociation from beta-arrestins and rapid recycling to the cell surface. Paradoxically, the apelin receptor internalized by apelin-36 was sequestered intracellularly. The specific pathways involved in apelin receptor trafficking were resolved using beta-arrestin1 and constitutively active and dominant negative Rab proteins following activation by apelin-13 or apelin-36. beta Arrestin1 dissociated from the apelin-13-internalized receptor while the apelin 36-internalized receptor was trafficked with beta-arrestin1 to intracellular compartments. The apelin-13-internalized receptor was rapidly recycled to the cell surface through a Rab4-dependent mechanism while Rab7 targeted the receptor to lysosomes. The internalized receptor co-expressed with dominant negative Rab4 were trafficked to lysosomes. These observations revealed a novel ligand dependent targeting of the apelin receptor to beta-arrestin-associated and dissociated trafficking pathways and a role for different Rab proteins to direct these pathways. PMID- 20353755 TI - Neuropoietin activates STAT3 independent of LIFR activation in adipocytes. AB - Neuropoietin (NP) is a member of the gp130 cytokine family that is closely related to cardiotrophin-1(CT-1) and shares functional and structural features with other family members, including ciliary neurotrophic factor (CNTF) and cardiotrophin-like cytokine (CLC). Studies have shown that NP can play a role in the development of the nervous system, as well as affect adipogenesis and fat cell function. However, the signaling mechanisms utilized by NP in adipocytes have not been examined. In our present studies, we demonstrate that NP-induced activation of STAT3 tyrosine phosphorylation is independent of leukemia inhibitory factor receptor (LIFR) phosphorylation and degradation. Although it is widely accepted that NP signals via the LIFR, our studies reveal that NP results in phosphorylation of gp130, but not LIFR. These observations suggest that the profound effects that NP has on adipocytes are not mediated via LIFR signaling. PMID- 20353757 TI - Actin stress fibers are at a tipping point between conventional shortening and rapid disassembly at physiological levels of MgATP. AB - Stress fibers (SFs) composed of nonmuscle actin and myosin II play critical roles in various cellular functions such as structural remodeling in response to changes in cell stress or strain. Previous studies report that SFs rapidly disassemble upon loss of tension caused by reduced myosin activity or sudden cell shortening, but the mechanism is unclear. Here, we showed that Rho-kinase inhibition with Y-27632 led to detachment of intact actin filaments from the SFs rather than depolymerization. Loss of tension may allow SFs to shorten via MgATP driven cross-bridge cycling, thus we investigated the effects of MgATP concentration on SF shortening and stability. We performed the experiments using extracted SFs to allow control over MgATP concentration. SF contraction and disassembly rates each increased with increasing MgATP concentration. SFs transitioned from conventional SF shortening to rapid disassembly as MgATP concentration increases from 2 to 5mM, which is within the physiological range of intracellular MgATP concentrations. Thus, we submit that SFs in intact cells are inherently on the verge of disassembly, which is likely due to the small number of actomyosin cross-bridges in SFs compared to those found in relatively stable myofibrils. Given that recent studies have revealed that loss of resistive force against myosin II could lower the fraction of the MgATPase cycle time that the myosin head is attached to actin (i.e., the duty ratio), binding of cytoplasmic levels of MgATP to myosin II may be sufficient to cause the disassembly of unloaded SFs. The present study thus describes a putative mechanism for rapid SF disassembly caused by decreased myosin activity or sudden cell shortening. PMID- 20353756 TI - Advanced glycation end-products affect transcription factors regulating insulin gene expression. AB - Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic beta-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression. PMID- 20353758 TI - Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non syndromic and aminoglycoside-induced hearing loss. AB - Mutations in mitochondrial DNA have been reported as associated with non syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycoside-induced hearing loss associated mutations. PMID- 20353759 TI - The insular cortex modulates cardiovascular responses to acute restraint stress in rats. AB - Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, which are characterized by blood pressure and heart rate increases. In the present study, we tested the hypothesis that insular cortex mediates cardiovascular responses to acute restraint stress in rats. To that purpose, the insular cortex synaptic transmission was inhibited by bilateral microinjection of the nonselective synaptic blocker cobalt chloride (CoCl2, 1 mM/100 nL). Insular cortex pretreatment with CoCl2 decreased restraint-evoked pressor and tachycardiac responses, thus indicating an involvement of synapses within the insular cortex on the modulation of cardiovascular responses to restraint stress. The present results indicate that insular cortex synapses exert a facilitatory influence on blood pressure and HR increase evoked by acute restraint stress in rats. PMID- 20353760 TI - Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macacafascicularis. AB - Mesenchymal stem cell (MSC) transplantation has been reported to improve neurologic function after ischemic injury. However, the detailed mechanisms by which MSCs promote functional recovery are not fully understood. Interleukin-10 (IL-10) is a well-known anti-inflammatory cytokine with neuroprotective effects with respect to brain injury. In this study, a non-human primate ischemia model was used to test the hypothesis that transplanted human bone-marrow-derived MSCs (hBMSCs) exert a neuroprotective effects on cerebral ischemia and upregulate IL 10 expression. We also assessed neuronal apoptosis and astroglial activity in the area around the ischemic lesion and proliferating cells in the subventricular zone (SVZ). Results showed that hBMSC transplantation in ischemic tissues improved the neurological functions and induced an increase in IL-10 expression. In addition, neuronal apoptosis and astroglial activity in the peri-ischemic area decreased, and the number of proliferating cells in the SVZ increased. These results provide a novel therapeutic strategy for improving neurologic function after cerebral ischemia. PMID- 20353761 TI - GABAergic dysfunction in mGlu7 receptor-deficient mice as reflected by decreased levels of glutamic acid decarboxylase 65 and 67kDa and increased reelin proteins in the hippocampus. AB - Glutamate is the main excitatory neurotransmitter in the brain, while gamma aminobutyric acid (GABA) is a primary inhibitory neuromodulator. Both amino acids act through ionotropic and metabotropic receptors that are widely distributed in the central nervous system. There are at least eight subtypes of metabotropic glutamate receptors (mGlu), which have been divided into three groups (mGlu I, II, and III). The mGlu7 receptor subtype, which belongs to the mGlu III group, seems to play a special role, as it is abundant in brain structures that are known to be responsible for antidepressant and/or anxiolytic activity of drugs. In GABAergic neurons, GABA is synthesised from glutamate by the pyridoxal phosphate (PLP)-dependent enzyme glutamic acid decarboxylase (GAD). It is expressed as two major isoforms, GAD65 and GAD67, responsible for the synthesis of the vesicular and cytoplasmic pool of neurotransmitter, respectively. Moreover, GABAergic neurons express a variety of proteins such as reelin, involved in synaptic transmission and plasticity. The aim of our study was to investigate the regulation of GABA synthesis and the level of modulatory receptor for GABA in mice lacking mGlu7 receptor for glutamate. The levels of GAD mRNA, GADs, and reelin proteins in the hippocampi of mGlu7-/- and mGlu7-/+ mice were measured using in situ hybridisation, immunohistochemistry, and Western blotting (WB). GAD mRNAs in the CA and DG regions of the hippocampus were measured separately. The levels of GAD65, GAD67, and reelin proteins were determined in the homogenates using WB, and the number of stained neurons was estimated using a stereological method of counting. GABA(B) receptor level was measured using a radioligand binding assay. Our results show that the mRNA and protein levels of both GADs were decreased in the hippocampi of animals lacking the mGlu7 receptor. Decreased levels of GAD67 mRNA were found in both the CA and DG regions, while the decrease in GAD65 mRNA was observed mainly in the CA region of the hippocampus. The protein levels of GAD65 was lowered in mGlu7-/- animals only, while GAD67 and GABA(B) receptor number were decreased in both mGlu7+/- and mGlu7 /- mice when measured in the whole hippocampus. In contrast, reelin was shown to be increased both in mGlu7-/+ and mGlu7-/- mice. The results suggest that mGlu7 receptor is involved in the regulation of GABAergic system activity at the level of GABA synthesised enzymes, specific proteins expressed by GABAergic neurons and metabotropic receptor for GABA. PMID- 20353762 TI - SK channel blocker apamin attenuates the effect of SSRI fluoxetine upon cell firing in dorsal raphe nucleus: a concomitant electrophysiological and electrochemical in vivo study reveals implications for modulating extracellular 5 HT. AB - A dual probing methodology was implemented so that combined in vivo voltammetric (electrochemical) and in vivo electrophysiological analysis could be carried out concomitantly in two distinct brain regions of the same anaesthetized animal, i.e., cell body such as the dorsal raphe nucleus (DRN) and related terminal region such as the hippocampus, the frontal cortex, and the amygdala. In particular, this methodology allowed: In addition, the dual probing methodology has been applied to verify the original proposal that a combined treatment with a potassium (SK) channel blocker such as apamin and an SSRI (i.e., fluoxetine) could overcome the slow onset of the SSRI upon central 5-HT activity that could be related to the slow onset of its therapeutic action. Briefly, the effect of apamin either alone or followed by fluoxetine upon cell firing in the DRN (in vivo electrophysiology) and concomitantly upon 5-HT levels (in vivo voltammetry) in the amygdala (forebrain structure involved in mood regulation and innervated by ascending 5-HT projections from the DRN) was studied. PMID- 20353763 TI - Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats. AB - N-methyl-d-aspartate (NMDA) receptor antagonists appear to enhance the anticonvulsant activity of antiepileptic drugs in several models of epilepsy. Therefore, the current study evaluates the modulatory effect of magnesium (Mg(2+)), a non-competitive NMDA receptor antagonist, on a subprotective dose of valproate (VPA) against pentylenetetrazol (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (60mg/kg, i.p.). The other three groups were pretreated with Mg(2+) (40mg/kg, p.o., 4weeks), single subprotective dose of VPA (100mg/kg, i.p.), or Mg(2+) with VPA, before PTZ injection. PTZ provoked clonic convulsions, reduced GABA content, deranged brain redox status, and elevated nitric oxide (NO). Neither the subprotective dose of VPA nor Mg(2+) alone guarded against clonic seizures invoked by PTZ, an effect that was achieved only by their combination and supported by a significant delay in seizure latency. Moreover, VPA leveled off glycine and aspartate, exerted no effect on glutamate, and unexpectedly reduced GABA and taurine levels. Mg(2+) alone or in combination showed the same pattern on the aforementioned amino acids, except for taurine. All regimens restored glutathione (GSH) and total antioxidant capacity (TAC); however, only VPA normalized NO level. This study demonstrates that Mg(2+) could enhance the antiepileptic efficacy of a subprotective dose of VPA, possibly by improving redox balance and modulation of some brain amino acids. PMID- 20353765 TI - Evolutionary origin of the Otx2 enhancer for its expression in visceral endoderm. AB - In the mouse, the Otx2 gene has been shown to play essential roles in the visceral endoderm during anterior-posterior axis formation and head induction. While these are primary processes in vertebrate embryogenesis, the visceral endoderm is a tissue unique to mammals. Two enhancers (VE and CM) have been previously found to direct Otx2 expression during early embryogenesis. This study demonstrates that in anterior visceral endoderm the CM enhancer does not have an activity by itself, but enhances the activity of the VE enhancer. These two enhancers also cooperate for the activities in anterior mesendoderm and cephalic mesenchyme. Comparative studies suggest that VE enhancer function was most likely established before the divergence of sarcopterygians into Actinistia, Dipnoi and tetrapods, while the nucleotide sequence corresponding to the VE enhancer was already present in the last common ancestor of bony fishes. The CM enhancer sequence and function would have been also established in ancestral sarcopterygians. The VE/CM enhancers and their gene cascades in the ancestral sarcopterygian head organizer would then have been co-opted by amphibian deep endoderm cells and mammalian visceral endoderm cells for the head development. PMID- 20353764 TI - Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. AB - Metabolic homeostasis reflects the complex output of endocrine, autonomic, and behavioral control circuits that extend throughout the central nervous system. Brain regions that control food intake and energy expenditure are privy to continuous visceral sensory feedback signals that presumably modulate appetite, satiety, digestion, and metabolism. Sensory signals from the gastrointestinal tract and associated digestive viscera are delivered to the brain primarily by vagal afferents that terminate centrally within the caudal nucleus of the solitary tract (NST), with signals subsequently relayed to higher brain regions by parallel noradrenergic and peptidergic projection pathways arising within the NST. This article begins with an overview of these ascending pathways identified in adult rats using a standard anterograde tracer microinjected into the caudal visceral sensory region of the NST, and also by immunocytochemical localization of glucagon-like peptide-1. NST projection targets identified by these two approaches are compared to the distribution of neurons that become infected after inoculating the ventral stomach wall with a neurotropic virus that transneuronally infects synaptically-linked chains of neurons in the anterograde (i.e., ascending sensory) direction. Although the focus of this article is the anatomical organization of axonal projections from the caudal visceral NST to the hypothalamus and limbic forebrain, discussion is included regarding the hypothesized role of these projections in modulating behavioral arousal and coordinating endocrine and behavioral (i.e., hypophagic) responses to stress. PMID- 20353766 TI - Angiotensin II type 1 receptor blockers prevent tumor necrosis factor-alpha mediated endothelial nitric oxide synthase reduction and superoxide production in human umbilical vein endothelial cells. AB - Decrease in endothelial nitric oxide synthase (eNOS) expression is one of the adverse outcomes of endothelial dysfunction. Tumor necrosis factor-alpha (TNF alpha) is known to decrease eNOS expression and is an important mediator of endothelial dysfunction. We hypothesized that an angiotensin II type 1 (AT1) receptor blocker would improve endothelial function via not only inhibition of the angiotensin II signaling but also inhibition of the TNF-alpha-mediated signaling. Therefore we investigated whether an AT1 receptor blocker would restore the TNF-alpha-induced decrease in eNOS expression in cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with an antioxidant (superoxide dismutase, alpha-tocopherol) or AT1 receptor blockers (olmesartan or candesartan) restored the TNF-alpha-dependent reduction of eNOS. The AT1 receptor blocker decreased the TNF-alpha-dependent increase of 8 isoprostane. The superoxide dismutase activities in HUVEC were stable during AT1 receptor blocker treatment, and the AT1 receptor blocker did not scavenge superoxide directly. The AT1 receptor blocker also decreased TNF-alpha-induced phosphorylation of I kappaB alpha and cell death. These results suggest that AT1 receptor blockers are able to ameliorate TNF-alpha-dependent eNOS reduction or cell injury by inhibiting superoxide production or nuclear factor-kappaB activation. PMID- 20353767 TI - Eupatolide inhibits lipopolysaccharide-induced COX-2 and iNOS expression in RAW264.7 cells by inducing proteasomal degradation of TRAF6. AB - Inula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of I kappaB alpha, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-kappaB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions. PMID- 20353768 TI - Effects of lipopolysaccharide on P-glycoprotein expression and activity in the liver and kidneys. AB - There have been many reports that P-glycoprotein expression and activity are altered during sepsis, but few of them have examined such changes over 72 h. In this study, we examined the effect of lipopolysaccharide (LPS, 5mg/kg, ip) on P glycoprotein expression (Western blotting) and activity (rhodamine-123 (Rho123) pharmacokinetics) in liver and kidneys for 7 days. On day 1 after LPS administration, hepatic P-glycoprotein expression and activity significantly decreased. On day 3, hepatic P-glycoprotein expression significantly increased compared with the control group, while activity had returned to the control level. On day 7, hepatic P-glycoprotein expression returned to the control level. There were no significant changes in P-glycoprotein expression or activity in the kidneys after LPS administration. The amount of Rho123 excretion in urine remained unchanged with (4.2%) or without (4.0%) LPS administration, but the amount of Rho123 excretion in bile decreased from 2.0 to 0.7% with LPS administration. Our findings suggested that hepatic P-glycoprotein expression and activity decreased on day 1 but recovered within 3 days, but there were no significant differences in the kidneys after LPS administration. These results suggested that the change in P-glycoprotein activity might be due to change in P glycoprotein expression in the liver rather than the kidneys. PMID- 20353769 TI - Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways. AB - Osteoclasts are specialized bone-resorbing cells derived from multipotent myeloid progenitor cells. They play a crucial homeostatic role in skeletal modeling and remodeling and destroy bone in many pathologic conditions. Receptor activator of NF-kappaB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of Ikarisoside A, isolated from Epimedium koreanum (Berberidaceae), on osteoclastogenesis in RANKL-treated murine monocyte/macrophage RAW 264.7 cells. The results indicate that Ikarisoside A is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW 264.7 cells as well as in bone marrow-derived macrophages. The inhibitory effect of Ikarisoside A resulted in decrease of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), tartrate-resistant acid phosphatase (TRAP), receptor activator of NF kappaB (RANK), and cathepsin K. Moreover, Ikarisoside A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Ikarisoside A also has inhibitory effects on the RANKL-mediated activation of NF-kappaB, JNK, and Akt. Finally, Ikarisoside A clearly decreased the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) as well as the transcriptional activity of NFATc1, the master regulator of osteoclast differentiation. The data indicate that Ikarisoside A has potential for use in treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone erosion. PMID- 20353770 TI - Murine erythropoietic impairment induced by paclitaxel: interactions of GATA-1 and erythroid Kruppel-like transcription factors, apoptotic related proteins and erythropoietin receptor. AB - Paclitaxel, an antitumoral drug, was used in a single dose (29 mg/kg i.p.) as an injury agent for inducing transient suppression of hematopoiesis in a murine experimental model during 10days. The aim of this study focuses on erythropoietin (EPO) receptor, GATA binding protein 1 (globin transcription factor 1) (GATA-1) and erythroid Kruppel-like factor (EKLF) expressions related to the apoptotic events triggered by paclitaxel in bone marrow and the subsequent in vivo erythropoietic recovery. Results showed a massive impairment of erythropoiesis early post paclitaxel administration (1-2 days), which involved induction of high Bax/Bcl-x(L) ratio, caspase-3 activation, disruptions of the medullar niche and cell death by both apoptosis and necrosis. EPO receptor over-expression was noticed from day 3 onwards. It prompted the subsequent up-regulations of GATA-1 and EKLF transcription factors as well as of the anti apoptotic protein Bcl-x(L), crucial proteins in driving erythropoiesis. This study suggests that EPO receptor recovery is necessary for the subsequent bone marrow ability to accomplish the erythroid program through the modulation of apoptotic and survival events after a single paclitaxel insult. These findings contribute to new insights into the molecular mechanisms involved during in vivo erythropoiesis post paclitaxel administration. Therefore, the detailed knowledge of the injury elicited by this drug on red blood cell production may have clinical relevance to explore new therapeutic approaches. PMID- 20353771 TI - Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. AB - Acylethanolamides are formed in the brain "on demand" from membrane phospholipids called N-acylated phosphatidylethanolamines. The acylethanolamides are signaling molecules of lipid nature, and this lipofilicity suggests an autocrine function. The acylethanolamides include palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamide (SEA), and several other quantitative minor species including anandamide (= arachidonoylethanolamide). PEA and OEA can activate several different receptors and inhibit some ion channels, e.g., PPARalpha, vanilloid receptor, K(+) channels (Kv4.3, Kv1.5), and OEA can activate GPR119 and inhibit ceramidases. Targets for SEA are less clear, but it has some cannabimimetic actions in rats in vivo. All acylethanolamides accumulate during neuronal injury, and injected OEA has neuroprotective effects, and PEA has anti inflammatory effects as studied in the peripheral system. Several of the pharmacological effects seem to be mediated via activation of PPARalpha. Recently, injected OEA has been found to consolidate memories in rats. Inhibitors of the acylethanolamide-degrading enzyme FAAH can increase levels of all acylethanolamides including annandamide, and some of the pharmacological effects caused by these inhibitors may be explained by increased cerebral levels of OEA and PEA, e.g., suppression of nicotine-induced activation of dopamine neurons. Furthermore, through activation of PPARalpha, OEA and PEA may stimulate neurosteroid synthesis, thereby modulating several biological functions mediated by GABA(A) receptors. The existence of acylethanolamides in the mammalian brain has been known for decades, but it is first within the last few years that the putative biological functions of the three most abundant acylethanolamides species are starting to emerge. PMID- 20353772 TI - Modulation of the endocannabinoid system: neuroprotection or neurotoxicity? AB - There is now a large volume of data indicating that compounds activating cannabinoid CB(1) receptors, either directly or indirectly by preventing the breakdown of endogenous cannabinoids, can protect against neuronal damage produced by a variety of neuronal "insults". Given that such neurodegenerative stimuli result in increased endocannabinoid levels and that animals with genetic deletions of CB(1) receptors are more susceptible to the deleterious effects of such stimuli, a case can be made for an endogenous neuroprotective role of endocannabinoids. However, this is an oversimplification of the current literature, since (a) compounds released together with the endocannabinoids can contribute to the neuroprotective effect; (b) other proteins, such as TASK-1 and PPARalpha, are involved; (c) the CB(1) receptor antagonist/inverse agonist rimonabant has also been reported to have neuroprotective properties in a number of animal models of neurodegenerative disorders. Furthermore, the CB(2) receptor located on peripheral immune cells and activated microglia are potential targets for novel therapies. In terms of the clinical usefulness of targeting the endocannabinoid system for the treatment of neurodegenerative disorders, data are emerging, but important factors to be considered are windows of opportunity (for acute situations such as trauma and ischemia) and the functionality of the target receptors (for chronic neurodegenerative disorders such as Alzheimer's disease). PMID- 20353773 TI - The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy. AB - The enzyme cyclooxygenase-2 (COX-2), which catalyzes the production of pro inflammatory prostaglandins, is induced in the brain after various insults, thus contributing to brain inflammatory processes involved in the long-term consequences of such insults. Mounting evidence supports that inflammation may contribute to epileptogenesis and neuronal injury developing after brain insults. Anti-inflammatory treatments, such as selective COX-2 inhibitors, may thus constitute a novel approach for anti-epileptogenesis or disease-modification after brain injuries such as head trauma, cerebral ischemia or status epilepticus (SE). However, recent rat experiments with prophylactic administration of two different COX-2 inhibitors after SE resulted in conflicting results. In the present study, we evaluated whether treatment with parecoxib, a pro-drug of the highly potent and selective COX-2 inhibitor valdecoxib, alters the long-term consequences of a pilocarpine-induced SE in rats. Parecoxib was administered twice daily at 10 mg/kg for 18 days following SE. Five weeks after termination of treatment, spontaneous recurrent seizures were recorded by continuous video/EEG monitoring. Prophylactic treatment with parecoxib prevented the SE-induced increase in prostaglandin E(2) and reduced neuronal damage in the hippocampus and piriform cortex. However, the incidence, frequency or duration of spontaneous seizures developing after SE or the behavioral and cognitive alterations associated with epilepsy were not affected by parecoxib. Only the severity of spontaneous seizures was reduced, indicating a disease-modifying effect. These results substantiate that COX-2 contributes to neuronal injury developing after SE, but inhibition of COX-2 is no effective means to modify epileptogenesis. PMID- 20353774 TI - Complexity of subthalamic 13-35 Hz oscillatory activity directly correlates with clinical impairment in patients with Parkinson's disease. AB - Excessive synchronization of the basal ganglia neuronal activity in the 13- to 35 Hz frequency band, so-called beta activity, has been associated with the motor deficits of Parkinson's disease (PD). Studies have demonstrated that beta activity may be suppressed by treatment with dopaminergic medication and high frequency stimulation of the subthalamic nucleus (STN), with the degree of suppression correlating with clinical improvement. However, these studies failed to demonstrate any correlation between beta activity of parkinsonism in the resting, untreated state. This argues against a significant relationship between beta activity and motor impairment. Here we use an advanced nonlinear dynamical analysis method based on the Lempel-Ziv estimator to show frequency band and symptom-subset specific correlations between STN local field potential (LFP) complexity and motor impairment in PD patients. Oscillatory activity has a reduced complexity, and we found a strong negative correlation between the complexity of the STN LFP over the 13- to 35-Hz frequency range and akinesia rigidity. There was no such correlation with tremor. Furthermore, there was no correlation between LFP Lempel-Ziv complexity (LZC) over the 0- to 12-Hz frequency band and any parkinsonian motor impairment. The results strengthen the association between the dynamic structure of synchonised (LFP) activity in the beta frequency band in the STN and akinesia-rigidity. PMID- 20353775 TI - The endocannabinoid system: a new entry in remote cell death mechanisms. AB - Functional impairment after development of focal CNS lesions depends highly on damage that occurs in regions that are remote but functionally connected to the primary lesion site. These remote effects include cell death and structural changes, and they are important predictors of outcome in several pathologies, such as stroke, multiple sclerosis, and brain trauma. A greater understanding of the neuropathological mechanisms that exist in regions that are remote from focal primary lesions is therefore essential for the development of neuroprotective strategies. Endocannabinoids constitute a novel class of lipids that regulate mammalian cell apoptosis and the pathogenesis of neuroinflammatory and neurodegenerative diseases. In addition to well-described pharmacological actions in the brain, such as analgesia, hypokinesia, and hypothermia, endocannabinoids have been recently reported to control neuronal cell fate in various neuropathological conditions. Following brain injury, endocannabinoids are released, causing both protective and degenerative effects. Several hypotheses have been proposed to explain their role, but the mechanisms by which they act are largely unknown. New evidence indicates that the endocannabinoid system is a key participant in the determination of cell fate in remote cell death and its associated mechanisms. This review addresses recent findings on endocannabinoid function, focusing particularly on the relationships between the nitrergic, purinergic, and endocannabinoid systems. PMID- 20353776 TI - The endocannabinoid system and nondrug rewarding behaviours. AB - Rewarding behaviours such as sexual activity, eating, nursing, parenting, social interactions, and play activity are conserved strongly in evolution, and they are essential for development and survival. All of these behaviours are enjoyable and represent pleasant experiences with a high reward value. Remarkably, rewarding behaviours activate the same brain circuits that mediate the positive reinforcing effects of drugs of abuse and of other forms of addiction, such as gambling and food addiction. Given the involvement of the endocannabinoid system in a variety of physiological functions of the nervous system, it is not surprising that it takes part in the complex machinery that regulates gratification and perception of pleasure. In this review, we focus first on the role of the endocannabinoid system in the modulation of neural activity and synaptic functions in brain regions that are involved in natural and nonnatural rewards (namely, the ventral tegmental area, striatum, amygdala, and prefrontal cortex). Then, we examine the role of the endocannabinoid system in modulating behaviours that directly or indirectly activate these brain reward pathways. More specifically, current knowledge of the effects of the pharmacological manipulation of the endocannabinoid system on natural (eating, sexual behaviour, parenting, and social play) and pathological (gambling) rewarding behaviours is summarised and discussed. PMID- 20353777 TI - Alcohol and endocannabinoids: neuroendocrine interactions in the reproductive axis. AB - Marihuana and alcohol consumption affect adversely reproduction by inhibiting the hypothalamic-pituitary-gonadal axis. The endocannabinoid system, present in the central nervous system and in peripheral tissues, participates in the regulation of hormones involved in the reproductive physiology such as luteinizing hormone, prolactin and oxytocin. This system is activated in response to pathophysiological conditions such as stress and inflammatory/infectious states as well as alcoholism and drug consumption acting as a negative modulator of reproductive function. The secretion of luteinizing hormone from the adenohypophysis is reduced, mainly through hypothalamic inhibitory action of cannabinoids and alcohol on luteinizing hormone releasing hormone release from its nervous terminals in the median eminence. This inhibitory effect is mediated, at least in part, by the activation of cannabinoid type 1 receptors. Cannabinoids also inhibit prolactin release from the lactotropes in the adenohypophysis acting locally and by increasing the release of hypothalamic dopamine mainly from tuberoinfundibular dopaminergic neurons in the external layer of the median eminence. On the contrary, ethanol stimulates prolactin release from the adenohypophysis as well as oxytocin from the neurohypophysis. Besides, endocannabinoids modulate oxytocin synthesis and release from the hypothalamic magnocellular neurons and neurohypophysis. In summary, all the results exposed in the present review suggest that there is interplay between the endocannabinoid system, hormones and neuropeptides in the control of reproduction and that this system mediates, at least in part, ethanol adverse effects on reproductive function. PMID- 20353778 TI - The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. AB - Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic diseases of the central nervous system (CNS), featured by a complex interplay between inflammation and neurodegeneration. Increasing evidence supports the involvement of the endocannabinoid system (ECS) in both inflammatory and neurodegenerative processes typical of these pathological conditions. Exogenous or endogenous cannabinoids regulate the function of immune system by limiting immune response. On the other hand, by preventing excitotoxic damage, cannabinoids protect neuronal integrity and function. Of note, the ECS not only plays a role as modulator of disease processes, but it can also be disrupted by the same diseases. Agents modulating cannabinoid receptors or endocannabinoid tone provide promising therapeutic opportunities in the treatment of inflammatory neurodegenerative disorders of the CNS. PMID- 20353779 TI - The endocannabinoid system in gp120-mediated insults and HIV-associated dementia. AB - Endocannabinoids (eCBs) include a group of lipid mediators that act as endogenous agonists at cannabinoid (CB(1), CB(2)) and vanilloid (TRPV1) receptors. In the last two decades a number of eCBs-metabolizing enzymes have been discovered that, together with eCBs and congeners, target receptors and proteins responsible for their transport and intracellular trafficking form the so-called "endocannabinoid system" (ECS). Within the central nervous system ECS elements participate in neuroprotection against neuroinflammatory/neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. More recently, a role for eCBs has been documented also in human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120-mediated insults, and in HIV-associated dementia (HAD). The modulation of ECS in the latter disease conditions is the subject of this review, that will also address the molecular mechanisms underlying the neuroprotective effects of eCBs. In particular, the interactions between neurons and glia during neuroinflammation, and the alterations of ECS in these cells upon gp120 insults and HAD will be discussed, along with the potential therapeutic exploitation of ECS-oriented drugs for the treatment of HAD and related disorders. PMID- 20353780 TI - The endocannabinoid system and migraine. AB - The recently discovered endocannabinoid system (ECS), which includes endocannabinoids and the proteins that metabolize and bind them, has been implicated in multiple regulatory functions both in health and disease. Several studies have suggested that ECS is centrally and peripherally involved in the processing of pain signals. This finding is corroborated by the evidence that endocannabinoids inhibit, through a cannabinoid type-1 receptor (CB1R)-dependent retrograde mechanism, the release of neurotransmitters controlling nociceptive inputs and that the levels of these lipids are high in those regions (such as sensory terminals, skin, dorsal root ganglia) known to be involved in transmission and modulation of pain signals. In this review we shall describe experimental and clinical data that, intriguingly, demonstrate the link between endocannabinoids and migraine, a neurovascular disorder characterized by recurrent episodic headaches and caused by abnormal processing of sensory information due to peripheral and/or central sensitization. Although the exact ECS-dependent mechanisms underlying migraine are not fully understood, the available results strongly suggest that activation of ECS could represent a promising therapeutical tool for reducing both the physiological and inflammatory components of pain that are likely involved in migraine attacks. PMID- 20353781 TI - The endocannabinoid system and amyloid-related diseases. AB - The endocannabinoid system may be the target of novel therapies in a wide variety of diseases. Among them, those related with amyloid accumulation will be discussed in the present review. Several components of this system (CB1 and CB2 receptors, endocannabinoids, FAAH enzyme) may participate in different aspects of amyloid pathophysiology such as, for instance, synaptic activity, cell migration, cytokine production or phagocytic activity. Consistent with recent data, putative lines of research and hypothesis will be discussed. PMID- 20353783 TI - The endocannabinoid system and psychiatric disorders. AB - The present review summarizes the latest information on the role and the pharmacological modulation of the endocannabinoid system in mood disorders and its potential implication in psychotic disorders such as schizophrenia. Reduced functionality might be considered a predisposing factor for major depression, so boosting endocannabinoid tone might be a useful alternative therapeutic approach for depressive disorders. The picture regarding endocannabinoids and anxiety is more complicated since either too much or too little anandamide can lead to anxiety states. However, a small rise in its level in specific brain areas might be beneficial for the response to a stressful situation and therefore to tone down anxiety. This effect might be achieved with low doses of cannabinoid indirect agonists, such as blockers of the degradative pathway (i.e. FAAH) or re uptake inhibitors. Moreover several lines of experimental and clinical evidence point to a dysregulation of the endocannabinoid system in schizophrenia. The high anandamide levels found in schizophrenic patients, negatively correlated with psychotic symptoms, point to a protective role, whereas the role of 2 arachidonoyl glycerol is still unclear. There is a potential for pharmacological manipulation of the endocannabinoid system as a novel approach for treating schizophrenia, although experimental findings are still controversial, often with different effects depending on the drug, the dose, the species and the model used for simulating positive or negative symptoms. Besides all these limitations, SR141716A and cannabidiol show the most constant antipsychotic properties in dopamine- and glutamate-based models of schizophrenia, with profiles similar to an atypical antipsychotic drug. PMID- 20353784 TI - Endocannabinoid signaling in healthy and diseased brain. PMID- 20353782 TI - Neuroprotection by glutamate receptor antagonists against seizure-induced excitotoxic cell death in the aging brain. AB - We previously have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death among two inbred strains of mice. We have also reported that the age-related increased susceptibility to the neurotoxic effects of seizure-induced injury is regulated in a strain-dependent manner. In the present study, we wanted to begin to determine the pharmacological mechanism that contributes to variability in the response to the neurotoxic effects of kainate. Thus, we compared the effects of the NMDA receptor antagonist, MK-801 and of the AMPA receptor antagonist NBQX on hippocampal damage in the kainate model of seizure-induced excitotoxic cell death in young, middle-aged, and aged C57BL/6 and FVB/N mice, when given 90 min following kainate-induced status epilepticus. Following kainate injections, mice were scored for seizure activity and brains from mice in each age and antagonist group were processed for light microscopic histopathologic evaluation 7 days following kainate administration to evaluate the severity of seizure-induced injury. Administration of MK-801 significantly reduced the extent of hippocampal damage in young, mature and aged FVB/N mice, while application of NBQX was only effective at attenuating cell death in young and aged mice throughout all hippocampal subfields. Our results suggest that both NMDA and non-NMDA receptors are involved in kainate-induced cell death in the mouse and suggest that aging may differentially affect the ability of neuroprotectants to protect against hippocampal damage. Differences in the effectiveness of these two antagonists could result from differential regulation of glutamatergic neurotransmitter systems or ion channel specificity. PMID- 20353785 TI - Endocannabinoids and voluntary activity in mice: runner's high and long-term consequences in emotional behaviors. AB - The endocannabinoid system participates in the regulation of physical activity, although its role is not yet fully understood. Here, we highlight the impact of endocannabinoid signalling on voluntary wheel running in mice and discuss potential mechanisms involved such as hippocampal neurogenesis. Running-induced short-term and long-term alterations of emotional behaviors are scrutinized with regard to the question how endocannabinoids might be involved. While endocannabinoids seem to contribute to the motivational aspects of voluntary running in rodents, influencing the total distance covered most likely via CB1 receptors, they are less involved in the long-term changes of emotional behavior induced by voluntary exercise. PMID- 20353786 TI - p24 family type 1 transmembrane proteins are required for insulin biosynthesis and secretion in pancreatic beta-cells. AB - The p24 protein family have multiple functions in protein transport in the early secretory pathway. In this study we examined the role of p24 proteins in insulin transport. Several members were detected in insulinoma cell lines and rat islets and expression levels positively correlated with insulin abundance, particularly for p24delta1 and p24beta1. Knocking down p24delta1 in insulinoma cell lines, which also resulted in the concomitant knock-down of other family members, impaired glucose-stimulated insulin secretion, decreased total cellular insulin content and reduced proinsulin biosynthesis. There was no effect on overall protein biosynthesis or ER stress. These results suggest that p24delta1 and possibly other p24 family proteins are required for normal insulin biosynthesis and subsequent secretion in pancreatic beta-cells. PMID- 20353787 TI - ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells. AB - Following our previous finding that sodium selenite induces apoptosis in human leukemia NB4 cells, we now show that the expression of the critical antioxidant enzyme manganese superoxide dismutase (MnSOD) is remarkably elevated during this process. We further reveal that reactive oxygen species (ROS), especially superoxide radicals, play a crucial role in selenite-induced MnSOD upregulation, with extracellular regulated kinase (ERK) and p53 closely implicated. Specifically, ERK2 translocates into the nucleus driven by ROS, where it directly phosphorylates p53, leading to dissociation of p53 from its inhibitory protein mouse double minute 2 (MDM2). Active p53 directly mediates the expression of MnSOD, serving as the link between ERK2 translocation and MnSOD upregulation. PMID- 20353788 TI - Rac1 modulates TGF-beta1-mediated epithelial cell plasticity and MMP9 production in transformed keratinocytes. AB - Transforming growth factor-beta1 (TGF-beta1) activates Rac1 GTPase in mouse transformed keratinocytes. Expression of a constitutively active Q61LRac1 mutant induced an epithelial to mesenchymal transition (EMT) linked to stimulation of cell migration and invasion. On the contrary, expression of a dominant-negative N17TRac1 abolished TGF-beta1-induced cell scattering, migration and invasion. Moreover, Q61LRac1 enhanced metalloproteinase-9 (MMP9) production to levels comparable to those induced by TGF-beta1, while N17TRac1 was inhibitory. TGF beta1-mediated EMT involves the expression of the E-cadherin repressor Snail1, regulated by the Rac1 and mitogen-activated protein kinase (MAPK) pathways. Furthermore, MMP9 production was MAPK-dependent, as the MEK inhibitor PD98059 decreased TGF-beta1-induced MMP9 expression and secretion in Q61LRac1 expressing cells. We propose that regulation of TGF-beta1-mediated plasticity of transformed keratinocytes requires the cooperation between the Rac1 and MAPK signalling pathways. PMID- 20353789 TI - Beta-2 adrenergic receptor mediated ERK activation is regulated by interaction with MAGI-3. AB - The beta-2 adrenergic receptor (beta2AR) has a carboxyl terminus motif that can interact with PSD-95/discs-large/ZO1 homology (PDZ) domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel binding partner of beta2AR. The carboxyl terminus of beta2AR binds with high affinity to the fifth PDZ domain of MAGI-3, with the last four amino acids (D-S-L-L) of the receptor being the key determinants of the interaction. In cells, the association of full-length beta2AR with MAGI-3 occurs constitutively and is enhanced by agonist stimulation of the receptor. Our data also demonstrated that beta2AR-stimulated extracellular signal-regulated kinase 1/2 (ERK1/2) activation was substantially retarded by MAGI-3 expression. These data suggest that MAGI-3 regulates beta2AR-mediated ERK activation through the physical interaction between beta2AR and MAGI-3. PMID- 20353790 TI - Multiple clusters of hepatitis virus infections associated with anesthesia for outpatient endoscopy procedures. AB - BACKGROUND & AIMS: Hepatitis B virus (HBV) and hepatitis C virus (HCV) can be transmitted during administration of intravenous anesthesia when medication vials are used for multiple patients using incorrect technique. We investigated an outbreak of acute HBV and HCV infections among patients who received anesthesia during endoscopy procedures from the same anesthesiologist (anesthesiologist 1), in 2 different gastroenterology clinics. METHODS: Chart reviews, patient interviews, clinic site visits and infection control assessments, and molecular sequencing of patient isolates were performed. Patients treated by anesthesiologist 1 on specific procedure days were offered testing for blood borne pathogens. Endoscopy and anesthesia procedures were reviewed; HCV quasispecies analysis was performed. RESULTS: Six cases of outbreak-associated HCV infection and 6 cases of outbreak-associated HBV infection were identified in clinic 1. One outbreak-associated HCV infection was identified in clinic 2. HCV quasispecies sequences from the patients were nearly identical (96.9%-100%) to those from source patients with chronic viral hepatitis. All affected patients in both clinics received propofol from anesthesiologist 1, who inappropriately used a single-patient-use vial of propofol for multiple patients. Reuse of syringes to redose patients, with resulting contamination of medication vials used for subsequent patients, likely resulted in viral transmission. CONCLUSIONS: Twelve persons acquired HBV and HCV infections (6 hepatitis C, 5 hepatitis B, and 1 coinfection) in 2 separate offices as a result of receiving anesthesia from anesthesiologist 1. Gastroenterologists are urged to review carefully the injection, medication handling, and other infection control practices of all staff under their supervision, including providers of anesthesia services. PMID- 20353791 TI - Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. AB - BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) has been divided into subtypes 1 (lymphoplasmacytic sclerosing pancreatitis) and 2 (idiopathic duct centric pancreatitis). We compared clinical profiles and long-term outcomes of types 1 and 2 AIP. METHODS: We compared clinical presentation, relapse, and vital status of 78 patients with type 1 AIP who met the original HISORt criteria and 19 patients with histologically confirmed type 2 AIP. RESULTS: At presentation, patients with type 1 AIP were older than those with type 2 AIP (62 +/- 14 vs 48 +/- 19 years; P < .0001) and had a greater prevalence of increased serum levels of immunoglobulin G4 (47/59 [80%] vs 1/6 [17%]; P = .004). Patients with type 1 were more likely than those with type 2 to have proximal biliary, retroperitoneal, renal, or salivary disease (60% vs 0; P < .0001). Inflammatory bowel disease was associated with types 1 and 2 (6% vs 16%; P = .37). During median clinical follow-up periods of 42 and 29 months, respectively, 47% of patients with type 1 and none of those with type 2 experienced a relapse. In type 1 AIP, proximal biliary involvement (hazard ratio [HR], 2.12; P = .038) and diffuse pancreatic swelling (HR, 2.00; P = .049) were predictive of relapse, whereas pancreaticoduodenectomy reduced the relapse rate (vs the corticosteroid treated group; HR, 0.15; P = .0001). After median follow-up periods of 58 and 89 months (types 1 and 2, respectively), the 5-year survival rates for both groups were similar to those of the age- and sex-matched US population. CONCLUSIONS: Types 1 and 2 AIP have distinct clinical profiles. Patients with type 1 AIP have a high relapse rate, but patients with type 2 AIP do not experience relapse. AIP does not affect long-term survival. PMID- 20353792 TI - Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. AB - BACKGROUND & AIMS: Drugs that inhibit gastric acid might increase the risk of hip fracture. However, little long-term exposure data exist and no large studies have been conducted in the United States. METHODS: We conducted a case-control study using data from an integrated health services organization. We evaluated 33,752 patients with incident diagnoses of hip/femur fractures (cases), 130,471 matched members without fractures (controls), prescription data for use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) (up to 10 years' cumulative duration), and confounders. RESULTS: Patients with hip fractures were more likely than controls to have previously received a > or =2-year supply of PPIs (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.21-1.39) or H2RAs (OR, 1.18; 95% CI, 1.08-1.29). The risk was reduced after discontinuation of medication (OR of 1.30 [95% CI, 1.21-1.41] for current PPI users vs OR of 1.09 [95% CI, 0.64-1.85] for patients who received their last prescription 2-2.9 years ago). Higher dosages (but not increasing cumulative durations) were associated with increased risk (eg, > or =1.5 pills/day: OR, 1.41 [95% CI, 1.21-1.64]; <0.74 pills/day: OR, 1.12 [95% CI, 0.94-1.33]). Excess fracture risk for PPI use was only present among persons with at least one other fracture risk factor. CONCLUSIONS: Use of drugs that inhibit gastric acid is associated with an increased risk of hip fracture; however, this association was only found among persons with at least one other risk factor for hip fracture. Acid inhibition might therefore be associated with fracture risk in persons already at risk for osteoporosis, although other confounding cannot be excluded. PMID- 20353793 TI - SR Ca2+ store refill--a key factor in cardiac pacemaking. AB - This study presents a theoretical analysis of the role of store Ca(2+) uptake on sinoatrial node (SAN) cell pacemaking. Two mechanisms have been shown to be involved in SAN pacemaking, these being: 1) the membrane oscillator model where rhythm generation is based on the interaction of voltage-dependent membrane ion channels and, 2) the store oscillator model where cyclical release of Ca(2+) from intracellular Ca(2+) stores depolarizes the membrane through activation of the sodium-calcium exchanger (NCX). The relative roles of these oscillators in generation and modulation of pacemaker rate have been vigorously debated and have many consequences. The main new outcomes of our study are: 1) uptake of Ca(2+) by intracellular Ca(2+) stores increases the maximum diastolic potential (MDP) by reducing the cytosolic Ca(2+) concentration [Ca(2+)](c) and hence decreasing the NCX current; 2) this hyperpolarization enhances recruitment of key pacemaker currents (e.g. the hyperpolarization-activated HCN current (I(f)) and T-type Ca(2+) current (I(T-Ca))); 3) the resultant enhanced Ca(2+) entry during the pacemaker depolarization increases [Ca(2+)](c) causing advancement of the store Ca(2+) release cycle and increased NCX current. In overview, the novel feature of our study is an investigation of the role of store Ca(2+) uptake on SAN pacemaking. This occurs during the early diastolic period and causes enhanced I(f), I(T-Ca) and store release (and hence I(NCX)) during the later diastolic period. There is thus a symbiotic interaction between the two pacemaker "clocks" over the entire diastolic period, this providing robust and highly malleable SAN pacemaking. Accounting for store Ca(2+) uptake also provides insight into hitherto unexplained SAN behaviour, as we exemplify for the sinus bradycardia exhibited in catecholaminergic polymorphic ventricular tachycardia (CPVT). PMID- 20353794 TI - Phosphodiesterase 8A (PDE8A) regulates excitation-contraction coupling in ventricular myocytes. AB - In ventricular myocytes, activation of protein kinase A (PKA) by 3'-5' cyclic adenosine monophosphate (cAMP) increases the force of contraction by increasing L type Ca(2+) channel currents (I(Ca)) and sarcoplasmic reticulum (SR) Ca(2+) release during excitation-contraction coupling. Cyclic-nucleotide phosphodiesterases (PDEs) comprise a large family of enzymes whose role in the cell is to regulate the spatial and temporal profile of cAMP signals by controlling the degradation of this second messenger. At present, however, the molecular identity and functional roles of the PDEs expressed in ventricular myocytes are incompletely understood. Here, we tested the hypothesis that PDE8A plays a critical role in the modulation of at least one compartment of cAMP and hence PKA activity during beta-adrenergic receptor (betaAR) activation in ventricular myocytes. Consistent with this hypothesis, we found that PDE8A transcript and protein are expressed in ventricular myocytes. Our data indicate that evoked [Ca(2+)](i) transients and I(Ca) increased to a much larger extent in PDE8A null (PDE8A(-/-)) than in wild-type (WT) myocytes during beta-adrenergic signaling activation. In addition, Ca(2+) spark activity was higher in PDE8A(-/-) than in WT myocytes. Our data indicate that PDE8A is a novel cardiac PDE that controls one or more pools of cAMP implicated in regulation of Ca(2+) movement through cardiomyocyte. PMID- 20353795 TI - Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca(2+) calmodulin-dependent protein kinase II. AB - Increased cardiac ryanodine receptor (RyR)-dependent diastolic SR Ca leak is present in heart failure and in conditions when adrenergic tone is high. Increasing Ca leak from the SR could result in spontaneous Ca wave (SCaW) formation. SCaWs activate the inward Na/Ca exchanger (NCX) current causing a delayed afterdepolarization (DAD), potentially leading to arrhythmia. Here we examine SCaWs in ventricular myocytes isolated from failing and healthy rabbit hearts. Myocytes from healthy hearts did not exhibit SCaWs under baseline conditions versus 43% of those exposed to isoproterenol (ISO). This ISO-induced increase in activity was reversed by inhibition of Ca-calmodulin-dependent protein kinase II (CaMKII) by KN93. Inhibition of cAMP-dependent protein kinase (PKA) by H89 had no observed effect. Of myocytes treated with forskolin 50% showed SCaW activity, attributable to a large increase in SR Ca load ([Ca](SRT)) versus control. At similar [Ca](SRT) (121muM) myocytes treated with ISO plus KN93 had significantly fewer SCaWs versus those treated with ISO or ISO plus H89 (0.2+/-0.28 vs. 1.1+/-0.28 and 1.29+/-0.39 SCaWs cell(-)(1), respectively). In myocytes isolated from failing hearts ISO induced an increase in the percentage of cells generating SCaWs vs. baseline (74% vs. 11%) with no increase in [Ca](SRT). Inhibiting CaMKII reversed this effect (14%). At similar [Ca](SRT) (71microM) myocytes treated with ISO or ISO plus H89 had significantly more SCaWs per cell vs. untreated (2.5+/-0.5; 1.6+/-0.7 vs. 0.36+/-0.3, respectively). Treatment with ISO plus KN93 completely abolished this effect. The evidence suggests the ISO-dependent increase in SCaW activity in both healthy and failing myocytes is CaMKII-dependent, implicating CaMKII in arrhythmogenesis. PMID- 20353796 TI - Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era. AB - The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA)--i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence--using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes. PMID- 20353797 TI - Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells. AB - Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO(2) (As(3)(+)) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10 epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO(2), As(3)(+)) was found to produce immunosuppression at concentrations as low as 0.5 microM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na(2)HAsO(4), As(5)(+)). Coexposure of spleen cell cultures to PAHs and As(3)(+), both at individual low-effect concentrations, was found to produce profound suppression of the TDAR demonstrating synergy between these two chemical classes of agents. PMID- 20353798 TI - Segmentation by single and combined features involves different contextual influences. AB - Orientation discrimination of a texture line having orientation different from that of static background lines is facilitated when the lines are aligned along their orientation axis and when their separation is small (Experiment 1a). The facilitation by alignment remains when motion is added to the target (Experiment 1b). However, when the motion rather than the orientation has to be judged, alignment reduces sensitivity (d') regardless of whether the target has orientation the same as (iso-oriented) or different from background elements (Experiment 2). The inhibitory effect of alignment is confirmed when subjects have to discriminate the motion direction of an iso-oriented target (Experiment 3). Such inhibition by alignment is stronger when elements are close and may reflect a property of lateral interactions of motion detectors, since it is only present when observers have to judge the target motion direction. Overall, our results indicate an opposite role of the lateral interactions that facilitate grouping of iso-oriented and collinear elements, in segmentation by orientation contrast and motion contrast. In other words, global grouping (i) facilitates discrimination of orientation contrast, indicating a global process, and (ii) inhibits both detection and discrimination of motion contrast, suggesting the presence of a local process. PMID- 20353799 TI - Top-down projections to the primary visual areas necessary for object recognition: a case study. AB - We present a patient, who, following a right posterior ischemia, showed a selective deficit in visually recognising pictures, objects and faces. She was able to read and comprehend any kind of written material and could recognise letters and numbers. Her inability to recognise pictures did not arise from a deficit at the structural description level and/or from a poor semantic knowledge of the stimuli. We argue that her recognition deficit arose from an inability in combining the different elements of the visual stimuli in an unitary percept. Results are discussed in terms of dissociations between local versus global processing, as well as bottom-up versus top-down mechanisms. PMID- 20353800 TI - Conditional spatial-frequency selective pooling of one-dimensional motion signals into global two-dimensional motion. AB - This study examined spatial-frequency effects on a motion-pooling process in which spatially distributed local one-dimensional motion signals are integrated into the perception of global two-dimensional motion. Motion pooling over two- to three-octave frequency differences was found to be nearly impossible when all Gabor elements had circular envelopes, but possible when the width of high frequency elements was reduced, and the stimulus as a whole formed a closed contour configuration. These results are consistent with a view that motion pooling is controlled by form information, and that spatial-frequency difference is one, but not an absolute, form cue of segmentation. PMID- 20353801 TI - Early smoking initiation, sexual behavior and reproductive health - a large population-based study of Nordic women. AB - OBJECTIVE: To investigate associations between early smoking initiation, risk taking behavior and reproductive health. METHOD: A random sample of 69,486 women aged 18-45 from Denmark, Iceland, Norway and Sweden was surveyed in 2004-2005. We compared behavior and health among women who initiated smoking early (before age 15), later (at 15 or later) and never smokers. RESULTS: Adult women who initiated smoking early reported more lifetime and recent sexual partners and less condom use than women who initiated smoking later, and they had lower debut ages for coitus, pregnancy and alcohol consumption. Experiences of teenage pregnancy, abortion/miscarriage and having had at least one sexually transmitted infection (gonorrhea, herpes simplex, trichomonas vaginalis, chlamydia, genital warts) were more frequent among early than among later smoking initiators. Never smoking women reported fewer partners, later debut ages, and more condom use and were less likely to have experienced teenage pregnancy, abortion/miscarriage and having had at least one sexually transmitted infection than either group of smokers. CONCLUSION: Early smoking initiators were more likely to engage in risk taking behavior and experience adverse reproductive events than were smokers who initiated later. Age at smoking initiation may be an indicator of future reproductive health. Early smoking initiators represent targets for reproductive health information. PMID- 20353802 TI - Characterization of a rolling-circle replication plasmid pXY3 from Lactobacillus plantarum XY3. AB - The complete nucleotide sequence of cryptic plasmid pXY3 isolated from Lactobacillus plantarum strain XY3 has been determined. It consisted of a 2968-bp circular molecule with a G+C content of 39%. Sequence analysis of pXY3 revealed three putative open reading frames (ORFs). Based on sequence similarity, the Rep protein shared 89% and 88% identity with Rep proteins of pLF24 and pWCFS102, respectively, which belonged to the rolling-circle replication (RCR) pMV158 family. A ssoT-like single-strand origin (sso) and a typical pMV158 family double strand origin (dso) located upstream of the rep gene. Southern blot analysis indicated pXY3 replicate via a rolling-circle (RC) mechanism. Furthermore, the relative copy number of pXY3 was estimated to be about 97 copies per chromosome equivalent by real-time PCR. PMID- 20353803 TI - Quadruplex real-time quantitative PCR assay for the detection of pathogens related to late-onset ventilator-associated pneumonia: a preliminary report. AB - A quadruplex real-time (RT) qPCR assay for the detection and quantification in 4h of Staphylococcusaureus, Pseudomonasaeruginosa, Acinetobacterbaumannii and Stenotrophomonasmaltophilia directly from bronchoalveolar lavage specimens was developed. The specificity of the assay was 100% for all four species. PMID- 20353804 TI - Perspective: researching the transition from non-living to the first microorganisms: methods and experiments are major challenges. AB - Methods to research the origin of microbial life are limited. However, microorganisms were the first organisms on the Earth capable of cell growth and division, and interactions with their environment, other microbial cells, and eventually with diverse eukaryotic organisms. The origin of microbial life and the supporting scientific evidence are both an enigma and a scientific priority. Numerous hypotheses have been proposed, scenarios imagined, speculations presented in papers, insights shared, and assumptions made without supporting experimentation, which have led to limited progress in understanding the origin of microbial life. The use of the human imagination to envision the origin of life events, without supporting experimentation, observation and independently replicated experiments required for science, is a significant constraint. The challenge remains how to better understand the origin of microbial life using observations and experimental methods as opposed to speculation, assumptions, scenarios, envisioning events and un-testable hypotheses. This is not an easy challenge as experimental design and plausible hypothesis testing are difficult. Since past approaches have been inconclusive in providing evidence for the origin of microbial life mechanisms and the manner in which genetic instructions was encoded into DNA/RNA, it is reasonable and logical to propose that progress will be made when testable, plausible hypotheses and methods are used in the origin of microbial life research, and the experimental observations are, or are not reproduced in independent laboratories. These perspectives will be discussed in this article as well as the possibility that a pre-biotic film preceded a microbial biofilm as a possible micro-location for the origin of microbial cells capable of growth and division. PMID- 20353805 TI - IFNG +874T/A polymorphism and cytokine plasma levels are associated with susceptibility to Mycobacterium tuberculosis infection and clinical manifestation of tuberculosis. AB - Regarding the importance of interferon-gamma (IFN-gamma) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-gamma production, the present study investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis (TB). A total of 129 patients with pulmonary tuberculosis (PTB), 33 with extrapulmonary tuberculosis (EPTB), and 156 control subjects were studied. Blood samples were drawn and plasma was used to measure IFN-gamma serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leukocytes and used to investigate +874T/A polymorphism in IFNG gene using allele specific oligonucleotide-polymerase chain reaction. An association between the presence of the allele +874A and the genotype +874AA with the active tuberculosis was found (p < 0.0001, 95% confidence interval = 1.64-3.22), at the same time that allele + 874T and genotype +874T/T were more frequent in the control group. The average plasma concentration of IFN-gamma among patients with tuberculosis was significantly lower than in the control group, and were lower in the EPTB group than in the group with PTB, suggesting a relationship of low plasma levels of this cytokine with active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874T/T and +874A/A genotypes with high and low IFN-gamma plasma concentrations, respectively, both in TB patients and in the control groups. Thus our findings suggest an association of the IFNG +874T/A polymorphism with susceptibility to M. tuberculosis infection in the studied population. PMID- 20353806 TI - Association of HLA-DRB1*0405 with resistance to multibacillary leprosy in Taiwanese. AB - Host factors play an important role in determining the immune response and development of leprosy. The human leukocyte antigen system (HLA) has repeatedly been found to be associated with the pathogenesis of leprosy. This study analyzes the polymorphism of the HLA class I and II antigens in multibacillary leprosy patients and a healthy control group to provide predictable prognostic indicators and/or a differential diagnostic for the disease. Sixty-5 multibacillary leprosy patients from Lo-Sheng Leprosarium and 190 healthy Taiwanese were used as cases and controls, respectively. A serologic method was initially used for HLA-A and HLA-B antigen determination, and sequence-based typing was later applied for HLA DRB1 allele typing. Although no significant associations were found with HLA-A or HLA-B antigens, this study shows a strong HLA-DRB1*0405 association with resistance to multibacillary leprosy, supporting results previously reported in the literatures. PMID- 20353807 TI - The effects of ginseng total saponin, panaxadiol and panaxatriol on ischemia/reperfusion injury in isolated rat heart. AB - The aim of the present study was to evaluate the protective effect of ginseng total saponin, panaxadiol and panaxatriol, which are the major components of Panax ginseng, against myocardial ischemia/reperfusion (I/R) injury in isolated rat hearts. Rats were orally administered once a day with total saponin (20 mg/kg), panaxadiol (5 mg/kg) and panaxatriol (5 mg/kg) for consecutive 7 days. On day 8, the hearts were isolated and perfused with Krebs-Henseleit bicarbonate buffer solution using Langendorff apparatus. After 30 min of global ischemia, hearts were reperfused for 30 min. Myocardial function, coronary flow and biochemical parameters, such as lactate dehydrogenase (LDH), creatine kinase (CK), adenosine triphosphate (ATP), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Total saponin and panaxatriol significantly improved I/R induced myocardial dysfunction by increasing left ventricular development pressure, (-dP/dt)/(+dP/dt) and time to contracture. Moreover, the increases in the levels of LDH, CK and MDA and the decrease in the levels of GSH were attenuated by total saponin and panaxatriol. However, the ATP levels did not affected by total saponin, panaxadiol and panaxatriol pretreatment. Our findings suggest that pretreatment with ginseng total saponin, especially panaxatriol, ameliorates I/R-induced myocardial damage and this protection is caused by reducing oxidative stress. PMID- 20353808 TI - How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase? AB - Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52), a validated antibiotic target, catalyses the first committed step in the lysine biosynthetic pathway: the condensation reaction between (S)-aspartate beta-semialdehyde [(S)-ASA] and pyruvate via the formation of a Schiff base intermediate between pyruvate and the absolutely conserved active-site lysine. Escherichia coli DHDPS mutants K161A and K161R of the active-site lysine were characterised for the first time. Unexpectedly, the mutant enzymes were still catalytically active, albeit with a significant decrease in activity. The k(cat) values for DHDPS-K161A and DHDPS K161R were 0.06 +/- 0.02 s(-1) and 0.16 +/- 0.06 s(-1) respectively, compared to 45 +/- 3 s(-1) for the wild-type enzyme. Remarkably, the K(M) values for pyruvate increased by only 3-fold for DHDPS-K161A and DHDPS-K161R (0.45 +/- 0.04 mM and 0.57 +/- 0.06 mM, compared to 0.15 +/- 0.01 mM for the wild-type DHDPS), while the K(M) values for (S)-ASA remained the same for DHDPS-K161R (0.12 +/- 0.01 mM) and increased by only 2-fold for DHDPS-K161A (0.23 +/- 0.02 mM) and the K(i) for lysine was unchanged. The X-ray crystal structures of DHDPS-K161A and DHDPS-K161R were solved at resolutions of 2.0 and 2.1 A respectively and showed no changes in their secondary or tertiary structures when compared to the wild-type structure. The crystal structure of DHDPS-K161A with pyruvate bound at the active site was solved at a resolution of 2.3 A and revealed a defined binding pocket for pyruvate that is thus not dependent upon lysine 161. Taken together with ITC and NMR data, it is concluded that although lysine 161 is important in the wild-type DHDPS-catalysed reaction, it is not absolutely essential for catalysis. PMID- 20353809 TI - An efficient method for single hematopoietic stem cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells. AB - OBJECTIVE: To develop an efficient method for single hematopoietic stem cell (HSC) transplantation for high-level hematopoietic engraftment. MATERIALS AND METHODS: We combined single-cell sorting with short-term culture of putative HSCs. Mouse bone marrow cells that had been highly enriched for HSCs were individually deposited into a 96-well culture plate and incubated in the presence of mouse c-kit ligand and either mouse interleukin-11 or human recombinant granulocyte colony-stimulating factor. One week later, the resulting clones of cells were individually transplanted into lethally irradiated recipients. We also carried out time-course analysis of proliferation of the individual clones. Finally, we used micromanipulation of the paired progenies of the single cells and studied self-renewal and differentiation potentials of HSCs again in combination with transplantation. RESULTS: There was a correlation between clone size at day 7 of culture and engraftment at 2 months post-transplantation. Small clones, such as those consisting of <15 cells, often showed high-level multilineage engraftment, while clones consisting of > or =40 cells showed very low levels of engraftment. Daily observation of cell divisions of individual clones revealed that some HSCs are in the G(0) state for as long as 1 week, despite the presence of permissive cytokines. Studies using micromanipulation of paired progenies documented the ability of an HSC to generate two HSCs, as well as asymmetric cell divisions. CONCLUSIONS: Single-cell sorting combined with short-term culture of individual putative HSCs provides an efficient method for single HSC transplantation. Analyses of the kinetics of individual HSCs provided direct evidence for HSC cell-cycle dormancy, self-renewal, and expansion. PMID- 20353810 TI - Prenatal restraint stress: an in vivo microdialysis study on catecholamine release in the rat prefrontal cortex. AB - There is substantial evidence that prenatal exposure to adverse environmental conditions might lead to the psychiatric disorders that can appear in adolescence or in adulthood; vulnerability to drug addiction may increase as well. It is currently accepted that the alteration of catecholamine transmission in the prefrontal cortex plays a prominent role in the etiology of psychiatric disorders. We assessed basal and stimulated dopamine and noradrenaline extracellular concentration in the medial prefrontal cortex by means of microdialysis in awake male adolescent and young adult offspring of rats exposed to restraint stress in the last week of pregnancy. Catecholamine stimulation was obtained by amphetamine or nicotine. We observed that prenatal stress (PNS) did not change dopamine but decreased noradrenaline basal output in both adolescents and adults. Moreover, it decreased amphetamine stimulated dopamine output and increased amphetamine stimulated noradrenaline output. PNS decreased nicotine stimulated noradrenaline (but not dopamine output) in adults, though not in adolescents. These data show that PNS stress modifies prefrontal cortex catecholamine transmission in a complex and age dependent manner. Our results support the view that prenatal stress may be a contributing factor for the development of psychiatric disorders and that its effect may augment drug addiction vulnerability. PMID- 20353811 TI - The nucleus locus coeruleus/subcoeruleus affects the defensive-like, immobile posture following an air-puff startle reaction in the rat. AB - The air-puff startle is an example of a simple behavior in mammals. Following the startle reaction, rats assume a defensive-like, immobile posture (DIP) of approximately 2-5 s in length. The aim of the present study was to examine the effect of bilateral lesions of the nucleus locus coeruleus/subcoeruleus (LC/SC) on the DIP. Using male Sprague-Dawley rats, the DIP period in the air-puff startle was measured with a digital stop watch. The DIP period was defined as the time between the application of the air-puff stimuli and the first motion after the startle reaction. For air-puff stimulation (14.4 psi in strength, 0.1 s in duration), compressed house air was presented as a transient through a vinyl tube suspended 2.5 cm above the rat's head. Two weeks before the experiment, the rats received bilateral injections of 6 microg of the neurotoxin 6-hydroxydopamine to specifically lesion noradrenaline-containing neurons of the LC/SC. In the sham lesioned rats (n=8), the DIP period did not significantly alter compared with that before operation. In contrast, in the LC/SC-lesioned rats (n=9), the DIP period significantly reduced to 78% of the values before lesions. The results suggest that the LC/SC is involved in the development of the DIP. We speculate that the DIP period is an attentional state and vigilance condition because LC/SC neurons have been implicated in the regulation of the attentional state and vigilance. PMID- 20353812 TI - Glutamatergic axons from the lateral habenula mainly terminate on GABAergic neurons of the ventral midbrain. AB - The concept of cortical-subcortical loops emphasizes the importance of the basal ganglia for motor, psychomotor, and emotional cortical functions. These loops are bidirectionally controlled by the midbrain dopaminergic system, predominantly but not exclusively at the level of the striatum including the accumbens nucleus. Successful behaviors increase the activities of the mesostriatal (arising in the complex part of the substantia nigra) and mesolimbic (arising in the ventral tegmental area, VTA) neurons, thereby reinforcing the corresponding actions. In contrast, unsuccessful behaviors result in an increased activation of the lateral habenular complex (LHb), thereby decreasing the activities of mesolimbic neurons. Correspondingly, electrical stimulation of the LHb effectively blocks neuronal activity in the VTA. Whether this block is due to an inhibitory projection from the LHb to the VTA, or whether axons from excitatory LHb neurons target inhibitory neurons within the VTA, is presently not known. Here we show, using in situ hybridization and immunocytochemical double labeling at the light and electron microscopic level, that GABAergic neurons are scarce in the LHb and that glutamatergic axons from the LHb mostly target GABAergic neurons in the VTA and the mesopontine rostromedial tegmental nucleus (RMTg), also known as tail of the VTA (tVTA). These data explain the inhibitory effect of LHb activation on the VTA. In addition, however, a small number of LHb terminals in the VTA actually contacts dopaminergic neurons. The biological importance of these terminals requires further investigation. PMID- 20353813 TI - Structure and expression of myelin basic protein gene products in Xenopus laevis. AB - To study roles of the myelin basic protein (mbp) gene products in nervous system development, cDNA cloning and expression analyses were performed in Xenopus laevis. We cloned cDNAs for XMBP.1 and XMBP.2 encoded by xmbp.1 and xmbp.2 genes, respectively. We also identified xmbp.1 gene transcripts encoding three XGolli (X.laevis gene of the oligodendrocyte lineage) proteins, XBG21.1, XJ37.1, and XTP8.1, which are homologues of mouse BG21, J37, and TP8, respectively. In reverse transcription-polymerase chain reaction (RT-PCR) analyses, the XMBP, XJ37, and XTP8 mRNAs were expressed in brain, ovaries, testes, and/or thymus in frogs and in larvae after hatching. In contrast, the XBG21 mRNA was found fairly ubiquitously in adult tissues, unfertilized eggs and embryos throughout the developmental stages examined. Western blot analyses using three different monoclonal antibodies (mAbs) showed that the central and peripheral myelin contained 20kDa and18.5 kDa XMBP variants. In addition, XMBP was found in thymus by Western blotting and in thymocyte cytoplasm immunocytochemically. However, the XGolli protein, most provably XBG21, was detectable only in testes. The results indicate that the structure of xmbp gene products seems highly conserved among amphibians and mammals, although their expression patterns and thus physiological roles may partially differ. This is the first report that systematically describes the mbp gene products in nonmammalian vertebrates. PMID- 20353814 TI - Prediction of Polycomb target genes in mouse embryonic stem cells. AB - Polycomb group (PcG) proteins are important epigenetic regulators, yet the underlying targeting mechanism in mammals is still poorly understood. We have developed a computational approach to predict genome-wide PcG target genes in mouse embryonic stem cells. We use TF binding and motif information as predictors and apply the Bayesian Additive Regression Trees (BART) model for classification. Our model has good prediction accuracy. The performance can be mainly explained by five TF features (Zf5, Tcfcp2l1, Ctcf, E2f1, Myc). Our analysis of H3K27me3 and gene expression data suggests that genomic sequence is highly correlated with the overall PcG target plasticity. We have also compared the PcG target sequence signatures between mouse and Drosophila and found that they are strikingly different. Our predictions may be useful for de novo search for Polycomb response elements (PRE) in mammals. PMID- 20353815 TI - Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays. AB - Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. Results using whole genome Illumina microarrays show that ritonavir modulates a number of genes implicated in lipid metabolism, inflammation and atherosclerosis. These candidate genes are dual specificity phosphatase 1 DUSP1), Kelch domain containing 3 (KLHDC3), neutral cholesterol ester hydrolase 1 (NCEH1) and acyl-CoA synthetase short-chain family member 2 (ACSS2). Validation experiments using quantitative PCR showed that ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated these 4 selected candidate genes in 20 healthy individuals. Lower expression levels of these 4 candidate genes, known to play a critical role in inflammation, lipid metabolism and atherosclerosis, may explain ritonavir adverse effects in patients. PMID- 20353816 TI - Identification and characterization of human snoRNA core promoters. AB - Small nucleolar RNAs (snoRNAs) represent one of the largest groups of functional non-protein coding RNAs currently known in eukaryotic cells. The processing of intron encoded snoRNAs has been well documented; however, the transcriptional regulation of snoRNA genes is still poorly understood, most likely due to the lack of characterization of snoRNA promoters. Here we used a computational approach to predict core promoters for 131 human snoRNAs. Majority of putative snoRNA promoters are supported by DNase I hypersensitivities, RNA polymerase II ChIP-seq peaks, or CAGE tag clusters. Based on the genomic organizations of predicted human snoRNA promoters, we propose five transcriptional models of those snoRNA genes; we also found evidence that some intronic human snoRNAs might have their own promoters. The present study is the first in silico screening of human snoRNAs promoters; and we anticipate the data will facilitate further molecular characterization of transcriptional control of human snoRNA genes. PMID- 20353817 TI - Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. AB - Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all p<.05). During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p<.05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p<.01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p<.05). These results suggest a role for over-expressed pro-inflammatory cytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden. PMID- 20353819 TI - Reactive oxygen species: A radical role in development? AB - Reactive oxygen species (ROS), mostly derived from mitochondrial activity, can damage various macromolecules and consequently cause cell death. This ROS activity has been characterized in vitro, and correlative evidence suggests a role in various pathological conditions. In addition to this passive ROS activity, ROS also participate in cell signaling processes, though the relevance of this function in vivo is poorly understood. Throughout development, elevated cell activity is probably accompanied by highly active metabolism and, consequently, the production of large amounts of ROS. To allow proper development, cells must protect themselves from these potentially damaging ROS. However, to what degree ROS could participate as signaling molecules controlling fundamental and developmentally relevant cellular processes such as proliferation, differentiation, and death is an open question. Here we discuss why available data do not yet provide conclusive evidence on the role of ROS in development, and we review recent methods to detect ROS in vivo and genetic strategies that can be exploited specifically to resolve these uncertainties. PMID- 20353818 TI - Intrathecal injection of an alpha seven nicotinic acetylcholine receptor agonist attenuates gp120-induced mechanical allodynia and spinal pro-inflammatory cytokine profiles in rats. AB - Nicotinic acetylcholine receptors (nAchRs) are not only key receptors in the autonomic nervous system, but also are present on immune cells. The alpha seven subunit of nAchR (alpha7nAchR) suppresses pro-inflammation in peripheral monocytes by decreasing pro-inflammatory cytokine production. In spinal cord, alpha7nAchRs are found on microglia, which are known to induce and maintain pain. We predicted that alpha7nAchR agonists might attenuate intrathecal HIV-1 gp120 induced, pro-inflammatory cytokine- and microglia-dependent mechanical allodynia. Choline, a precursor for acetylcholine and selective agonist for alpha7nAchR, was administered intrathecally either with, or 30 min after, intrathecal gp120. Choline significantly blocked and reversed gp120-induced mechanical allodynia for at least 4 h after drug administration. In addition, intrathecal choline, delivered either with or 30 min after gp120, reduced gp120-induced IL-1beta protein and pro-inflammatory cytokine mRNAs within the lumbar spinal cord. A second alpha7nAchR agonist, GTS-21, also significantly reversed gp120-induced mechanical allodynia and lumbar spinal cord levels of pro-inflammatory cytokine mRNAs and IL-1beta protein. A role of microglia is suggested by the observation that intrathecal choline suppressed the gp120-induced expression of, cd11b, a macrophage/microglial activation marker. Taken together, the data support that alpha7nAchR may be a novel target for treating pain where microglia maintain the pro-inflammatory state within the spinal cord. PMID- 20353821 TI - Trans-4-hydroxy-2-hexenal, a product of n-3 fatty acid peroxidation: make some room HNE... AB - Lipid peroxidation yields multiple aldehyde species. Of these, trans-4-hydroxy-2 nonenal (HNE), derived from n-6 poly-unsaturated fatty acids (PUFA) is one of the most studied products of lipid peroxidation. On the other hand, oxidative damage to n-3 PUFA, e.g. docosahexaenoic acid (DHA; 22:6, n-3) and eicosapentaenoic acid, is now recognized as an important effector of oxidative stress and is of particular interest in n-3 rich tissues such as brain and retina. Trans-4-hydroxy 2-hexenal (HHE) is a major alpha,beta-unsaturated aldehyde product of n-3 PUFA oxidation and, like HNE, is an active biochemical mediator resulting from lipid peroxidation. HHE adducts are elevated in disease states, in some cases, at higher levels than the corresponding HNE adduct. HHE has properties in common with HNE, but there are important differences particularly with respect to adduction targets and detoxification pathways. In this review, the biochemistry and cell biology of HHE will be discussed. From this review, it is clear that further study is needed to determine the biochemical and physiological roles of HHE and its related aldehyde, trans-4-oxo-2-hexenal. PMID- 20353822 TI - The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts. AB - A high concentration of oxygen can cause lung injury and lead to pulmonary fibrosis. Angiotensin (Ang) II induces human lung fibroblast proliferation and stimulates collagen synthesis. However, the role of the renin-angiotensin system (RAS) in the pathogenesis of hyperoxia-induced collagen production is unclear. The aims of this study were to investigate the effects of hyperoxia on the components of the RAS and collagen expression in human lung fibroblasts (MRC-5). Hyperoxia increased total collagen, collagen type I, and alpha-smooth muscle actin (alpha-SMA) mRNA and protein expression. RAS components and Ang II production were also significantly increased after hyperoxic exposure. Hyperoxia induced Ang II type 1 receptor (AT1R) expression but did not alter AT2R expression, furthermore, silencing of AT1R signaling with small interfering RNA suppressed hyperoxia-induced phosphorylated-ERK (p-ERK) 1/2, alpha-SMA, and collagen type I expression. Ang II increased p-ERK 1/2 and collagen type I expression, and these increases were inhibited by the AT1R inhibitor, losartan, but not by the AT2R inhibitor, PD123319 under both normoxic and hyperoxic conditions. These data suggest Ang II-mediated signaling transduction via AT1R is involved in hyperoxia-induced collagen synthesis in human lung fibroblasts. PMID- 20353820 TI - A novel role for caveolin-1 in regulating endothelial nitric oxide synthase activation in response to H2O2 and shear stress. AB - Previous studies have shown that acute increases in oxidative stress induced by the addition of hydrogen peroxide (H(2)O(2)) can increase endothelial nitric oxide synthase (eNOS) catalytic activity via an increase in the phosphorylation of eNOS at serine 1177. However, it is unclear how increased H(2)O(2) affects nitric oxide (NO) signaling when endothelial cells are exposed to biomechanical forces. Thus, the purpose of this study was to evaluate the acute effects of H(2)O(2) on NO signaling in the presence or absence of laminar shear stress. We found that acute sustained increases in cellular H(2)O(2) levels in bovine aortic endothelial cells did not alter basal NO generation but the NO produced in response to shear stress was significantly increased. This amplification in NO signaling was found to correlate with an H(2)O(2)-induced increase in eNOS localized to the plasma membrane and an increase in total caveolin-1 protein levels. We further demonstrated that overexpressing caveolin-1 increased eNOS localized to the plasma membrane again without altering total eNOS protein levels. We also found that caveolin-1 overexpression increased NO generation in response to shear stress but only in the presence of H(2)O(2). Conversely, depleting caveolin-1 with an siRNA decreased eNOS localized to the plasma membrane and abolished the enhanced NO generation. Finally, we found that expressing a caveolin-1 binding-site deletion mutant of eNOS in COS-7 cells decreased its plasma membrane localization and resulted in attenuated NO production in response to calcium activation. In conclusion, we have identified a new role for caveolin-1 in enhancing eNOS trafficking to the plasma membrane that seems to be involved in priming eNOS for flow-mediated activation under conditions of oxidative stress. To our knowledge, this is the first report that H(2)O(2) modulates eNOS activity by altering its subcellular location and that caveolin-1 can play a stimulatory role in NO signaling. PMID- 20353823 TI - Stat1 mediates an auto-regulation of hsp90beta gene in heat shock response. AB - We have reported earlier that a heat shock element in the first intron of human hsp90beta gene (iHSE) acts as an intronic enhancer to bind the heat shock factor (HSF1) and activates hsp90beta gene under heat shock. Here, we show that, in addition to the HSF1, Stat1 phosphorylation is indispensable in the event. We show that Jak2, a Janus kinase specifically associated with the beta subunit of IFNgamma receptor, and PKCepsilon an isoform of the atypical PKC family, are the two dominant kinases responsible for the heat shock induced phosphorylation on Y701 and S727 of Stat1. However, the activation of these kinases under heat shock requires the association of chaperone proteins of the Hsp90 family, in particular, the Hsp90beta under heat shock. Furthermore, Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex is likely recruited by HSF1 and Stat1 at the iHSE under heat shock. Brg1 further confers an open chromatin conformation at the promoter region that is pivotal to the heat shock induced fully activation of the hsp90beta gene in Jurkat cells. This is a novel example of how multiple activation steps occur under heat shock, first on the kinases and then the Stat1 and the SWI/SNF chromatin remodeling complex that follows to conduct an auto regulation based fully activation of the gene. PMID- 20353824 TI - Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein. AB - A characteristic of the 7TM-cadherins, Flamingo and Celsr1, is their asymmetric protein distribution and polarized activity at neighboring epithelial cell interfaces along defined axes of planar cell polarity. Here, we describe a novel distribution of Celsr1 protein to the basal surface of neuroepithelial cells within both the early neural tube and a less well-defined group of ventricular zone cells at the midline of the developing spinal cord. Importantly, this basal enrichment is lost in embryos homozygous for a mutant Celsr1 allele. We also demonstrate an intimate association between basal enrichment of Celsr1 protein and dorsal sensory tract morphogenesis, an intriguing spatio-temporal organization of Celsr1 protein along the apico-basal neuroepithelial axis suggestive of multiple Celsr1 protein isoforms and the existence of distinct cell surface Celsr1 protein species with direct signaling potential. Together, these data raise compelling new questions concerning the role of Celsr1 during neural development. PMID- 20353825 TI - The random-model method enables ab initio 3D reconstruction of asymmetric particles and determination of particle symmetry. AB - Model-based, 3D reconstruction techniques depend on reliable starting models. We present an extension of the random-model method (RMM) that allows the ab initio generation of suitable starting models directly from un-averaged, experimental images of asymmetric or symmetric particles. Therefore, the asymmetric RMM can also be used to determine point-group symmetry. The procedure is facilitated by the use of (a) variable angular step-sizes during iterative origin and orientation searches, (b) high numbers of particle images, and (c) highly defocused images. The method is inhibited by mixed-handedness orientation assignments and by particles with inconspicuous features. For symmetric particles, symmetric RMMs can overcome these deficiencies. PMID- 20353826 TI - Crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase from the hyperthermophile Thermotoga maritima for insights into the coordination of conformational changes and an inhibitor binding. AB - Isopentenyl diphosphate is a precursor of various isoprenoids and is produced by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in plastids of plants, protozoa and many eubacteria. A key enzyme in the MEP pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), has been shown to be the target of fosmidomycin, which works as an antimalarial, antibacterial and herbicidal compound. In this paper, we report studies of kinetics and the crystal structures of the thermostable DXR from the hyperthermophile Thermotoga maritima. Unlike the mesophilic DXRs, Thermotoga DXR (tDXR) showed activity only with Mg(2+) at its growth temperature. We solved the crystal structures of tDXR with and without fosmidomycin. The structure without fosmidomycin but unexpectedly bound with 2 methyl-2,4-pentanediol (MPD), revealing a new extra space available for potential drug design. This structure adopted the closed form by rigid domain rotation but without the flexible loop over the active site, which was considered as a novel conformation. Further, the conserved Asp residue responsible for cation binding seemed to play an important role in adjusting the position of fosmidomycin. Taken together, our kinetic and the crystal structures illustrate the binding mode of fosmidomycin that leads to its slow, tight binding according to the conformational changes of DXR. PMID- 20353827 TI - Hippocampal volumetry for lateralization of temporal lobe epilepsy: automated versus manual methods. AB - The hippocampus has been the primary region of interest in the preoperative imaging investigations of mesial temporal lobe epilepsy (mTLE). Hippocampal imaging and electroencephalographic features may be sufficient in several cases to declare the epileptogenic focus. In particular, hippocampal atrophy, as appreciated on T1-weighted (T1W) magnetic resonance (MR) images, may suggest a mesial temporal sclerosis. Qualitative visual assessment of hippocampal volume, however, is influenced by head position in the magnet and the amount of atrophy in different parts of the hippocampus. An entropy-based segmentation algorithm for subcortical brain structures (LocalInfo) was developed and supplemented by both a new multiple atlas strategy and a free-form deformation step to capture structural variability. Manually segmented T1-weighted magnetic resonance (MR) images of 10 non-epileptic subjects were used as atlases for the proposed automatic segmentation protocol which was applied to a cohort of 46 mTLE patients. The segmentation and lateralization accuracies of the proposed technique were compared with those of two other available programs, HAMMER and FreeSurfer, in addition to the manual method. The Dice coefficient for the proposed method was 11% (p<10(-5)) and 14% (p<10(-4)) higher in comparison with the HAMMER and FreeSurfer, respectively. Mean and Hausdorff distances in the proposed method were also 14% (p<0.2) and 26% (p<10(-3)) lower in comparison with HAMMER and 8% (p<0.8) and 48% (p<10(-5)) lower in comparison with FreeSurfer, respectively. LocalInfo proved to have higher concordance (87%) with the manual segmentation method than either HAMMER (85%) or FreeSurfer (83%). The accuracy of lateralization by volumetry in this study with LocalInfo was 74% compared to 78% with the manual segmentation method. LocalInfo yields a closer approximation to that of manual segmentation and may therefore prove to be more reliable than currently published automatic segmentation algorithms. PMID- 20353828 TI - The "visual word form area" is involved in successful memory encoding of both words and faces. AB - Previous studies have identified the critical role of the left fusiform cortex in visual word form processing, learning, and memory. However, this so-called visual word form area's (VWFA) other functions are not clear. In this study, we used fMRI and the subsequent memory paradigm to examine whether the putative VWFA was involved in the processing and successful memory encoding of faces as well as words. Twenty-two native Chinese speakers were recruited to memorize the visual forms of faces and Chinese words. Episodic memory for the studied material was tested 3h after the scan with a recognition test. The fusiform face area (FFA) and the VWFA were functionally defined using separate localizer tasks. We found that, both within and across subjects, stronger activity in the VWFA was associated with better recognition memory of both words and faces. Furthermore, activation in the VWFA did not differ significantly during the encoding of faces and words. Our results revealed the important role of the so-called VWFA in face processing and memory and supported the view that the left mid-fusiform cortex plays a general role in the successful processing and memory of different types of visual objects (i.e., not limited to visual word forms). PMID- 20353829 TI - Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation. AB - Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome. Xerostomia was reported in 60 (77%) patients reporting ocular and 52 (67%) patients reporting oral complaints. The salivary flow rate was < or =0.2 mL/min in 27%, and < or =0.1 mL/min in 16%. Histopathological changes, consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had diminished oral cavity-specific quality of life and lower body mass index. Salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is needed, and this could be incorporated as an outcome measure in clinical trials of cGVHD. PMID- 20353830 TI - HIV status does not affect the outcome of autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL). AB - Randomized trials comparing autologous stem cell transplant (ASCT) to conventional chemotherapy have demonstrated superior survival among HIV-negative ASCT patients with relapsed non-Hodgkin lymphoma (NHL). Recent trials explored the feasibility of ASCT in the HIV setting. Although these studies have shown that ASCT in HIV-positive NHL patients (HIVpos-NHL) is well tolerated, the impact of HIV infection on long-term transplant outcome is not well characterized. Ongoing comparison of long-term survival following ASCT in HIVpos-NHL patients and HIVneg-NHL patients will allow investigators to explore whether there should be inclusion of HIVpos-NHL patients in ASCT trials. To study long-term outcome we conducted a single-institution matched case-controlled study in HIVpos-NHL patients (cases) and HIVneg-NHL patients (controls). Twenty-nine patients with HIVpos-NHL were matched with HIVneg-NHL controls on sex, time to ASCT, year of transplant, histology, age, disease status, number prior regimens, and conditioning regimen. Nonrelapse mortality (NRM) was similar: 11% (95% confidence interval [CI]: 4%-28%) in HIVpos-NHL patients and 4% (95% CI: 1%-25%) in HIVneg NHL controls (P = .18). Two-year disease-free survival (DFS) for the HIVpos-NHL patients was 76% (95% CI: 62%-85%) and 56% (95% CI: 45%-66%) for the HIVneg-NHL controls (P = .33). Overall survival was also similar; the 2-year point estimates were 75% (95% CI: 61%-85%) and 75% (95% CI: 60%-85%), respectively (P = .93), despite inclusion of more poor risk HIVpos-NHL patients. These results provide further evidence that HIV status does not affect the long-term outcome of ASCT for NHL, and therefore HIV status alone should no longer exclude these patients from transplant clinical trials. PMID- 20353831 TI - Impact of donor-recipient major ABO mismatch on allogeneic transplantation outcome according to stem cell source. AB - Major ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT), even if it can be associated with several immunohematologic complications. Nevertheless, conflicting data still exist as to its influence on graft-versus-host disease (GVHD) incidence, relapse rate, and survival. To further investigate the relevance of ABO major mismatch on transplantation outcome, we retrospectively analyzed results from 414 patients with major or major/minor ABO-mismatched bone marrow (BM), peripheral blood (PB), and cord blood (CB) allogeneic HSCT. Transplantation outcome was assessed by comparison with results from a 395 patient ABO-compatible population with similar characteristics. Median time to red cell transfusion independence was significantly longer in ABO-incompatible BM recipients (median time, 63 days vs 41 days; P =.001), with faster disappearance of antidonor IgM hemagglutinins in unrelated recipients (median time, 36 days vs 44 days; P = .03) and in patients with grade > or =II acute GVHD (aGVHD) (median time, 35 days vs 59 days ; P = .001). In PB stem cell (PBSC) and CB transplantation, erythroid reconstitution was not significantly delayed, regardless of donor type or presence of aGVHD. A slight correlation between ABO incompatibility and GVHD incidence was found in PBSC recipients when considering grade > or =II aGVHD incidence (63% in ABO-matched HSCT vs 83% in ABO-mismatched HSCT; P = .055), but this was not confirmed in multivariate analysis. In patients with acute leukemia, multivariate analysis revealed an association between major ABO mismatch and decreased relapse rate with borderline statistical significance (hazard ratio, 0.65; P = .04). Major ABO incompatibility mainly, if not exclusively, affects red blood cell engraftment after BM transplantation. Somewhat surprisingly, the graft-versus-plasma cell effect seems to be confined to this stem cell source. PMID- 20353832 TI - Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease. AB - Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) are important complications after allogeneic hematopoietic stem cell transplantation (HSCT) with a clear link. Multiple studies show that GVHD and its treatment put patients at risk for CMV replication. Data on CMV replication as a cause of GVHD, in contrast, are controversial. We analyzed the reciprocal association of CMV replication with acute GVHD (aGVHD) in 515 patients treated with allogeneic HSCT between 1993 and 2008. Cumulative incidences at day 100 were 17% for CMV replication, 68% for aGVHD grade I-IV, and 48% for GVHD grade II-IV. Multivariate time-dependent analyses revealed that the presence of GVHD increased the risk of CMV replication in a dose-dependent manner: hazard ratio (HR) for CMV replication for patients with aGVHD grade I was 1.35 (95% confidence interval [CI] 0.82 2.21); HR for patients with aGVHD grade II-IV was 1.61 (95% CI 1.11-2.36, P-value for trend = .01). During phases of CMV replication, patients were at increased risk of developing aGVHD (HR 2.18, 95% CI 1.30-3.65, P < .01). These data confirm that GVHD and its therapy can induce CMV replication. They further demonstrate the reciprocal novel finding that patients are at significantly increased risk of developing aGVHD during CMV replication. PMID- 20353833 TI - Degree of predicted minor histocompatibility antigen mismatch correlates with poorer clinical outcomes in nonmyeloablative allogeneic hematopoietic cell transplantation. AB - In fully HLA-matched allogeneic hematopoietic cell transplantation (HCT), the main mechanism of the beneficial graft-versus-tumor (GVT) effect and of detrimental graft-versus-host disease (GVHD) is believed to be caused by donor cytotoxic T cells directed against disparate recipient minor histocompatibility antigens (miHAs). The most common origin of disparate miHAs is nonsynonymous single nucleotide polymorphism (nsSNP) differences between donors and patients. To date, only some 30 miHAs have been identified and registered, but considering the many different HLA types in the human population, as well as all the possible nsSNP differences between any 2 individuals, it is likely that many miHAs have yet to be discovered. The objective of the current study was to predict novel HLA A- and HLA-B-restricted miHAs in a cohort of patients treated with nonmyeloablative conditioning allogeneic HCT (matched related donor, n = 70; matched unrelated donor, n = 56) for a hematologic malignancy. Initially, the cohort was genotyped for 53 nsSNPs in 11 known miHA source proteins. Twenty-three nsSNPs within 6 miHA source proteins showed variation in the graft-versus-host (GVH) direction. No correlation between the number of disparate nsSNPs and clinical outcome was seen. Next, miHAs in the GVH direction were predicted for each patient-donor pair. Using the NetMHCpan predictor, we identified peptides encompassing an nsSNP variant uniquely expressed by the patient and with predicted binding to any of the HLA-A or -B molecules expressed by the patient and donor. Patients with more than the median of 3 predicted miHAs had a significantly lower 5-year overall survival (42% vs 70%, P = .0060; adjusted hazard ratio [HR], 2.6, P = .0047) and significantly higher treatment-related mortality (39% vs 10%, P = .0094; adjusted HR, 4.6, P = .0038). No association between the number of predicted miHAs and any other clinical outcome parameters was observed. Collectively, our data suggest that the clinical outcome of HCT is affected not by disparate nsSNPs per se, but rather by the HLA-restricted presentation and recognition of peptides encompassing these. Our data also suggest that 6 of the 11 proteins included in the current study could contain more miHAs yet to be identified, and that the presence of multiple miHAs confers a higher risk of mortality after nonmyeloablative conditioning HCT. Furthermore, our data suggest a possible role for in silico based miHA predictions in donor selection as well as in selecting candidate miHAs for further evaluation in in vitro and in vivo experiments. PMID- 20353834 TI - Nanostructured surfaces for enhanced protein detection toward clinical diagnostics. AB - "Label-free" biomolecule sensors for detection of inflammatory cardiovascular biomarker associated with vulnerable coronary vascular plaque rupture were designed and fabricated using micro- and nanotextured polystyrene (PS) polymer structures that functioned as sensing elements coupled with electronic measurement equipment. We demonstrated that scaling down the surface texturing from the micro- to the nanoscale enhances the amplitude of the measured detected signal strength. We believe that the nanoscale fiber morphology provides size matched spaces for trapping and immobilizing the protein biomolecule, resulting in improved detection signal strength. We selected PS as the model system and demonstrated the detection of human serum C-reactive protein. We employed these findings in designing a platform "lab-on-a-chip" protein sensor. Comparative studies were performed on PS textured surfaces of two different surface features: a PS microsphere mat and an electrospun PS nanofiber matrix. FROM THE CLINICAL EDITOR: In this study, nanotechnology-based biosensors for vulnerable coronary vascular plaque rupture were designed and fabricated using micro- and nanotextured polystyrene polymer structures. The authors demonstrated that scaling down the surface texturing from the micro- to the nanoscale enhances the sensitivity of this detection method. PMID- 20353835 TI - Sinomenine pretreatment attenuates cold ischemia/reperfusion injury in rats: the role of heme oxygenase-1. AB - Ischemia/reperfusion (I/R) injury can be characterized as an inflammatory response including recruitment of inflammatory cells to a post-ischemic organ or tissue and a cascade of mediators. Sinomenine (SIN), a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum, has been used to treat various inflammatory diseases including rheumatism and arthritis. However, whether SIN can attenuate I/R injury has not previously been examined. Using a syngeneic orthotopic liver transplantation model in rats, we investigated the effect of SIN on hepatic I/R injury, in particular its effect on heme oxygenase-1 (HO-1) induction and its hepatocellular protective effect. To our knowledge, our results were the first to show that: (a) SIN pretreatment was able to induce HO-1 expression in donor livers in a dose dependent manner; (b) SIN pretreatment protected the liver graft from cold I/R injury; and (c) the protective effect of SIN was, at least in part, mediated by HO-1, as proved by the fact that inhibiting HO-1 activity with zinc protoporphyrin (ZnPP) reduced the protection. Thus, SIN deserves further exploration as a novel agent to attenuate I/R injury. PMID- 20353836 TI - Proteomic analysis of common bean seed with storage protein deficiency reveals up regulation of sulfur-rich proteins and starch and raffinose metabolic enzymes, and down-regulation of the secretory pathway. AB - A deficiency in major seed storage proteins is associated with a nearly two-fold increase in sulfur amino acid content in genetically related lines of common bean (Phaseolus vulgaris). Their mature seed proteome was compared by an approach combining label-free quantification by spectral counting, 2-DE, and analysis of selective extracts. Lack of phaseolin, phytohemagglutinin and arcelin was mainly compensated by increases in legumin, alpha-amylase inhibitors and mannose lectin FRIL. Along with legumin, albumin-2, defensin and albumin-1 were major contributors to the elevated sulfur amino acid content. Coordinate induction of granule-bound starch synthase I, starch synthase II-2 and starch branching enzyme were associated with minor alteration of starch composition, whereas increased levels of UDP-glucose 4-epimerase were correlated with a 30% increase in raffinose content. Induction of cell division cycle protein 48 and ubiquitin suggested enhanced ER-associated degradation. This was not associated with a classical unfolded protein response as the levels of ER HSC70-cognate binding protein were actually reduced in the mutant. Repression of rab1 GTPase was consistent with decreased traffic through the secretory pathway. Collectively, these results have implications for the nutritional quality of common bean, and provide information on the pleiotropic phenotype associated with storage protein deficiency in a dicotyledonous seed. PMID- 20353837 TI - Analytical proteomics: an emerging field? PMID- 20353838 TI - Transcription of mouse Sp2 yields alternatively spliced and sub-genomic mRNAs in a tissue- and cell-type-specific fashion. AB - The Sp-family of transcription factors is comprised by nine members, Sp1-9, that share a highly conserved DNA-binding domain. Sp2 is a poorly characterized member of this transcription factor family that is widely expressed in murine and human cell lines yet exhibits little DNA-binding or trans-activation activity in these settings. As a prelude to the generation of a "knock-out" mouse strain, we isolated a mouse Sp2 cDNA and performed a detailed analysis of Sp2 transcription in embryonic and adult mouse tissues. We report that (1) the 5' untranslated region of Sp2 is subject to alternative splicing, (2) Sp2 transcription is regulated by at least two promoters that differ in their cell-type specificity, (3) one Sp2 promoter is highly active in nine mammalian cell lines and strains and is regulated by at least five discrete stimulatory and inhibitory elements, (4) a variety of sub-genomic messages are synthesized from the Sp2 locus in a tissue- and cell-type-specific fashion and these transcripts have the capacity to encode a novel partial-Sp2 protein, and (5) RNA in situ hybridization assays indicate that Sp2 is widely expressed during mouse embryogenesis, particularly in the embryonic brain, and robust Sp2 expression occurs in neurogenic regions of the post-natal and adult brain. PMID- 20353840 TI - [Advances in respiratory health 2009: a view from SEPAR areas]. PMID- 20353841 TI - [Sleep respiratory disorders, non-invasive ventilation and critical care in Archivos de Bronconeumologia (June 2008-November 2009)]. AB - The present study analyses the works published in Archivos de Bronconeumologia from June 2008 to November 2009 that mention sleep disorders, non-invasive ventilation and critical care. The methodology used was to analyse the objectives of the works submitted, with their main results and the conclusions suggested by the authors, often putting forward the possibility of conducting new research studies. The review no only includes original articles but is also a reflection on the editorials, special articles and review works. PMID- 20353839 TI - Activation of NF-kappaB by fluid shear stress, but not TNF-alpha, requires focal adhesion kinase in osteoblasts. AB - When bone is mechanically loaded fluid shear stress (FSS) is generated as a result of the movement of interstitial fluid across the membranes of osteoblasts and osteocytes. This external mechanical loading stimulates changes in the activity of cytoplasmic signaling molecules and alters gene expression in bone cells. This process, referred to as mechanotransduction, is vital for maintaining bone health in vivo by regulating the balance between bone formation and bone resorption. This current study focuses on the role of focal adhesions, sites of integrin-mediated cellular attachment to the extracellular matrix, and their proposed function as mechanosensors in bone cells. We examined the role of a key component of focal adhesions and of mechanotransduction, focal adhesion kinase (FAK) in regulation of FSS- and tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappa B (NF-kappaB) signaling in osteoblasts. Immortalized FAK(+/+) and FAK(-)(/)(-) osteoblasts were exposed to periods of oscillatory fluid shear stress (OFF) and NF-kappaB activation was analyzed. We determined that FAK is required for OFF-induced nuclear translocation and activation of NF-kappaB in osteoblasts. In addition we found that OFF-induced phosphorylation of the IkappaB kinases (IKKalpha/beta) in both FAK(+/+) and FAK( /-) osteoblasts, but only FAK(+/+) osteoblasts demonstrated the resulting degradation of NF-kappaB inhibitors IkappaBalpha and IkappaBbeta. OFF did not induce the degradation of IkappaBepsilon or the processing of p105 in either FAK(+/+) and FAK(-/-) osteoblasts. To compare the role of FAK in mediating OFF induced mechanotransduction to the well characterized activation of NF-kappaB by inflammatory cytokines, we exposed FAK(+/+) and FAK(-/-) osteoblasts to TNF alpha. Interestingly, FAK was not required for TNF-alpha induced NF-kappaB activation in osteoblasts. In addition we determined that TNF-alpha treatment did not induce the degradation of IkappaBbeta as did OFF. These data indicate a novel relationship between FAK and NF-kappaB activation in osteoblast mechanotransduction and demonstrates that the mechanism of FSS-induced NF-kappaB activation in osteoblasts differs from the well characterized TNF-alpha-induced activation. PMID- 20353842 TI - [Hot topics respiratory infections]. AB - A critical review of articles on respiratory infections published in the last three months of 2008 to the end of 2009. There are articles on patients with bronchiectasis that study their quality of life, as well as those that analyse the decrease in the number of exacerbations due to the immunomodulatory effect of using low doses of macrolides in these patients. In the diagnosis of tuberculosis, works on the application of interferon-A are especially relevant, whilst on the treatment of this disease, articles that study therapeutic innovations in the management of TB-MDR and TB-XDR or -TDR are also highlighted. As far as publications on pneumonia are concerned, there are those that analyse the progression of community acquired pneumonias (CAP) in patients affected with chronic obstructive pulmonary disease. Furthermore, special importance is given to the initial epidemiological and clinical studies of the influenza A (H1N1) pandemic. Also of interest is the evaluation of prognostic scales as predictors of ventilation support and/or the use of pressor amines, as well as the use of biological markers to complement the predictive value of these prognostic scales. Aetiological and clinical studies of pneumonias associated with the health system continue to be of great interest and their possible differences compared to CAPs. Also of interest in the treatment of the pneumonias, is the analysis of the potential inflammation modulatory ability of different drugs. PMID- 20353843 TI - [Smoking. Analysis of the scientific production in the SEPAR smoking area in 2009]. AB - The SEPAR Smoking Area was started in the year 1995. Its main aims were to increase awareness of the problem of smoking among the members of our scientific society, to improve their scientific knowledge on this problem, to help in diagnostic and therapeutic interventions in smokers, and finally, to promote interventions for the prevention and treatment of smoking by the health and political administrations. Nowadays, it is the most dynamic areas of SEPAR and has more than 400 members. Throughout the year 2009, the health professionals of the SEPAR smoking area have carried out intense research work that has led to a reasonable scientific production that has covered different aspects of the discipline of smoking. The most impressive studies were those that tried to determine the impact that Law 28/2005 has had in the prevalence of smoking in Spain, the studies that assessed the scientific productivity of the area members and the numerous articles that published the results from different smoking units that are led by Spanish pneumologists. PMID- 20353844 TI - [Exposure to environmental contaminants and respiratory disease. Spotlight on the year 2009]. AB - The continued inhalation of contaminants present in the air that we breathe is a common cause of respiratory disease. Classically, this exposure-disease relationship has been proved in the workplace and as a cause of specific diseases such as pneumoconiosis and occupational asthma. However, there is increasing evidence indicating an association between occupational exposure and other more prevalent respiratory diseases such as Chronic Obstructive Pulmonary Disease and lung cancer. The effect of contamination is also observed outside the workplace. The air in cities can contribute to increasing the morbidity and mortality due to chronic respiratory diseases. Some articles published during the year 2009 that have a bearing on aspects associated with respiratory diseases of occupational or environmental origin are reviewed below. PMID- 20353845 TI - [Asthma in the Archivos de Bronconeumologia: a review of publications in the year 2009]. AB - A total of 16 articles (Table 1), were published in the Archivos de Bronconeumologia in the past year (December 2008 to November 2009), 9 of which were Originals, which was 17.6% of the originals published in that period. Fortunately, the tendency of a decreasing interest in asthma by pneumologists does not seem to have materialised as was feared a few years ago, on the contrary it seems that research is increasing. All articles that appeared in the journal during the period mentioned are reviewed. PMID- 20353846 TI - [Chronic obstructive pulmonary disease in Archivos de Bronconeumologia in the year 2009]. AB - Chronic obstructive pulmonary disease (COPD) continues to be a disease of special importance due to its great social impact arising from its high prevalence, its high morbidity and mortality and the high health costs it incurs. This has led to a great number of articles on different aspects associated with COPD each year. There is increasingly greater emphasis made of the systemic repercussions of the diseases and its comorbidity. In that same sense, tools are being sought to be able to make a more accurate prognosis of the diseases and assess other different aspects of lung function. Some standards on the quality of healthcare in COPD have also been published during this year, as well as some recommendations of the care of these patients in the advanced phase. An attempt is made in this article to summarise the more outstanding COPD articles published in Archivos de Bronconeumologia during the past year. PMID- 20353847 TI - [Thoracic surgery 2009]. AB - Started with tuberculosis and developed in parallel with smoking and cancer and under the protection of anaesthesia, thoracic surgery appeared in the 1980's as a specialty with a difficult long-term survival. However, with the development of lung transplant, tracheal surgery, the appearance of video-assisted thoracic surgery, along with the confirmation that despite the excellent progress of chemoradiotherapy, surgery continues to be the best option for curing lung cancer, means that it is currently a specialty of great growth and a wider scope in the future. PMID- 20353848 TI - [Journal of the year 2009 in interventionist pneumology, interstitial diseases and transplant]. AB - Endobronchial ultrasound bronchoscopy has been one of the most important contributions to the minimally invasive diagnosis and staging of mediastinal disease in the last few years. Two original works with linear and radial endobronchial ultrasound bronchoscopy published in the Archivos de Bronconeumologia are analysed. In pleural pathology, we have selected a multicentre study one the usefulness of an outpatient tunnelised pleural drainage in 63 patients with malignant neoplastic effusions. This technique was indicated in 20% when pleurodesis failed or was not indicated, and an overall symptomatic improvement was achieved in 95% of cases. In interstitial diseases, we highlight the article on the usefulness of BAL in the initial diagnosis of these diseases in a series of 562 patients studied over 14 years. The authors highlight the minimal invasiveness of the technique and its value which, when added to the radiological and clinical findings, enables these diseases to be managed without surgical biopsy in around 90% of cases. Finally, we highlight the works on lung transplant which analysed the value of interleukin-8 by BAL in the donor lung to detect sub-clinical involvement that could lead to a primary dysfunction of the lung graft, the risk factors associated to mortality in 92 lung transplant receivers due to emphysema and, lastly, the experience of the transplant in 15 patients with pulmonary arterial hypertension in an advanced functional class, with a peri-operative survival at 5 years of 40%. PMID- 20353849 TI - [Pulmonary circulation: contributions of the year 2009]. AB - A significant number of studies on pulmonary circulation diseases have been published in 2009 that are likely to have a notable clinical impact. Anticoagulant treatment is on the verge of a significant change with the arrival of new oral drugs that have an inhibitory effect over factor X (rivaroxaban, apixaban) or thrombin (dabigatran). New studies have shown an efficacy comparable to enoxaparin in the prevention of thromboembolic disease and in some cases a lower risk of haemorrhage. Also interesting is a study on the incidence of pulmonary thromboembolism in patients with chronic obstructive pulmonary disease, a little known aspect. A study that demonstrates some efficacy of rosuvastatin in the prevention of thromboembolic disease, something that could change our current practices. Pulmonary hypertension (PH) continues to produce numerous publications. One French study has shown a relatively low risk of developing PH in patients with systemic sclerosis over a period of 3 years. As regards treatment, ambrisentan seems to confirm it lower risk of hepatoxicity compared to other endothelin antagonists. A new phosphodiesterase-5 inhibitor, tadalafil, has made a strong impact on the PH scene during this year. Its results are similar to other oral drugs with a convenient posology. The surgical treatment of PH due to chronic thromboembolism in one of the hospitals of our country has been present with results that, particularly in the past few years, are perfectly comparable to other centres of excellence. To summarise, 2009 has continued to provide important news in the area of pulmonary circulation. PMID- 20353850 TI - [Detection of lymph node involvement and surgical treatment of pulmonary neoplastic processes. Current state of diagnostic and therapeutic procedures]. AB - An analysis is made of different publications associated with the surgical staging and treatment of primary and metastasic pulmonary neoplastic processes. A suitable treatment program is essential to determine lymph node involvement in patients with bronchogenic carcinoma. The indication and sequence of the procedure to use (CT-PET, transbronchial puncture, videomediastinoscopic ultrasound guided transbronchial needle aspiration) is evaluated in accordance to the sensitivity, specificity and positive and negative predictive value of the different methods. Another interesting challenge is to define the criteria for indicating a sublobar resection in certain tumours and patients. Different factors, age, lung function, tumour location and type of sublobar resection, are analysed. Levels of evidence and recommendations of the procedure are also considered. Surgical resection is an accepted therapeutic option in the treatment of colorectal cancer lung metastases. Its indication is based on acceptable survival rates and knowledge of the impact of various factors (interval free of disease, number of metastases, presence of liver metastasis, presence of lymph node involvement, or increased pre-operative levels of carcinoembryonic antigen), is analysed in detail. PMID- 20353851 TI - [Multidisciplinarity, interdisciplinarity, transdisciplinarity]. AB - Working in a team, concepts in transdisciplinarity, multidisciplinarity, and interdisciplinarity. Integrated research in a society immersed in care, where the aim is none other than to increase the quality of life of those people who need it, the participation of all as links in the same chain where the failure or lack of commitment by one of the parties can endanger any project of the procedure to relate scientific knowledge, extra-scientific experience and the practice of solving problems. PMID- 20353852 TI - [Introduction. Influenza A (H1N1)]. PMID- 20353853 TI - [Epidemiology of influenza A (H1N1) worldwide and in Spain]. AB - On June 11, 2009, the World Health Organization declared an established pandemic due to a new influenza virus A (H1N1) of swine origin. Initial cases were detected in Mexico in March and within 6 weeks the virus had spread worldwide. The transmissibility of influenza A (H1NA) is slightly higher than that of the seasonal virus, but its pathogenicity and virulence are low. The main target groups of this new virus have been children and young adults under 30 years old. Mortality has affected mainly persons aged between 20 and 50 years old. In areas with temperate climates, two epidemic waves have occurred. The first one, from mid-April to mid-August, affected Mexico, the United States and, consecutively, Spain, England, Japan, and other countries in the northern hemisphere. A few weeks later, coinciding with the beginning of the influenza season, the H1N1 epidemic started in the southern hemisphere countries, especially Argentina, Chile, Australia and New Zealand; in these countries, the epidemic finished at the end of September or October. The second wave affected the northern hemisphere, starting in the United States and Mexico at the beginning of September, and a few weeks later in European countries. In mid-December, this wave was considered to have ended, although some influenza activity persists. The intensity of this second wave was higher compared to the first one. PMID- 20353854 TI - [Influenza A (H1N1). Experience in the United States]. AB - Pneumonia and seasonal influenza have major repercussions on mortality, morbidity and costs worldwide. At the end of March 2009, an outbreak of influenza A (H1N1) was reported in Mexico that rapidly spread throughout the world, including the United States, reaching pandemic proportions. The activity of influenza A (H1N1) has reached levels higher than those reported in previous years, mainly affecting the pediatric population aged less than 18 years old. In addition, a group of comorbid conditions were more frequently associated in patients with severe influenza A (H1N1), including chronic pulmonary disease, immunosuppression, heart disease, obesity and pregnancy. The current pandemic has had a substantial impact on public health in the United States and in many other countries worldwide. Therefore, the present review aims to examine the North American experience of the influenza A (H1N1) epidemic, focussing chronologically on the epidemiology of the virus, high risk groups, diagnosis, vaccination and management. PMID- 20353855 TI - [Influenza A (H1N1): clinical manifestations and prophylactic and therapeutic indications]. AB - Influenza A (H1N1) was first diagnosed in Mexico and the United States in April 2009. The rapidity of its worldwide spread has alerted the health authorities and international scientific community. The usual clinical symptoms of this disease cannot be distinguished from those of seasonal influenza and include cough, fever, poor general status, odynophagia and muscular aches. To date, the hospitalization rate has been relatively low (less than 15%). Among the affected population, there are two groups with high morbidity and mortality: pregnant women and persons aged more than 65 years. Treatment consists of the neuroaminidase inhibitors oseltamivir, zanamivir and peramivir, which can help to reduce complications and symptom duration. Definitive diagnosis is based on reverse-transcriptase polymerase chain reaction techniques. The remaining treatment options consist of universal measures of isolation, antipyretics and rest. Mortality is less than 1% globally but seems to be higher in Latin America. The present study gathers the available information on the manifestations, diagnostic criteria and treatment/prophylaxis of the disease. PMID- 20353857 TI - [Issues in vaccination against influenza A in Spain]. AB - Given the threat of an avian influenza A (H5N1) pandemic, vaccines that could be used in a new influenza pandemic began to be developed in 2004. The possible pandemic scenarios included highly serious situations with high incidence and mortality. Due to the need for the greatest possible number of vaccines to be available in a short period of time, studies with "model" vaccines were started, which allowed the immunogenicity and safety of the vaccines to be determined before identifying which virus would cause the pandemic. The use of adjuvants also formed part of these strategies. Subsequently, studies with the pandemic A (H1N1) strain were performed and additional studies continue to be performed. The vaccination strategies adopted have not been aimed at containing the infection but rather at ameliorating its effects. The choice of candidate groups for vaccination was not made hastily but after evaluating a large body of information on the epidemiology of the disease and the characteristics of the available vaccines. The population to be vaccinated is basically the same as that recommended to undergo seasonal influenza vaccination. In the ethical context of primum non nocere special emphasis has been placed on the vaccination of health personnel. All the available information supports the safety of the adjuvants and preservatives used in some of the authorized vaccines, as stated by the World Health Organization and many other prestigious organizations. So far 65 million doses have been administered throughout the world and the various adverse events detected by surveillance systems have been similar to those observed with other influenza vaccines and those that could be expected among millions of persons. Lessons must be drawn from the course of the present pandemic and the strategies used to deal with this situation as there will be other pandemics. PMID- 20353858 TI - Collagenase injection as nonsurgical treatment of Dupuytren's disease: 8-year follow-up. AB - PURPOSE: Collagenase has been investigated in phase II and phase III clinical trials for the treatment of Dupuytren's disease. The purpose of this study is to report 8-year follow-up results in a subset of patients who had collagenase injection for the treatment of Dupuytren's contracture. METHODS: Twenty-three patients who participated in the phase II clinical trial of injectable collagenase were contacted by letter and phone. Eight patients were enrolled, completed a Dupuytren's disease questionnaire, and had independent examination of joint motion by a single examiner. RESULTS: Eight patients completed the 8-year follow-up study: 6 had been treated for isolated metacarpophalangeal (MCP) joint contracture, and 2 had been treated for isolated proximal interphalangeal (PIP) joint contracture. Average preinjection contracture was 57 degrees in the MCP group. Average contracture was 9 degrees at 1 week, 11 degrees at 1 year, and 23 degrees at 8-year follow-up. Four of 6 patients experienced recurrence, and 2 of 6 had no evidence of disease recurrence at 8-year follow-up. Average preinjection contracture was 45 degrees in the PIP group. Average contracture was 8 degrees at 1 weeks, 15 degrees at 1 year, and 60 degrees at 8-year follow-up. Both patients experienced recurrence at 8-year follow-up. No patients had had further intervention on the treated finger in either the MCP or the PIP group. Patients subjectively rated the overall clinical success at 60%, and 88% of patients stated that they would pursue further injection for the treatment of their recurrent or progressive Dupuytren's disease. CONCLUSIONS: Enzymatic fasciotomy is safe and efficacious, with initial response to injection resulting in reduction of joint contracture to within 0 degrees -5 degrees of normal in 72 out of 80 patients. Initial evaluation of long-term recurrence rates suggests disease recurrence or progression in 4 out of 6 patients with MCP contractures and 2 patients with PIP contractures; however, recurrence was generally less severe than the initial contracture in the MCP group. In addition, patient satisfaction was high. PMID- 20353859 TI - Blinded, prospective, randomized clinical trial comparing volar, dorsal, and custom thermoplastic splinting in treatment of acute mallet finger. AB - PURPOSE: To compare volar, dorsal, and custom splinting techniques in acute Doyle I mallet finger injuries. METHODS: We developed a radiographic lag measurement using the contralateral normal digit as an internal control for establishing the approximate preinjury maximal extension of the mallet finger. The difference in maximal distal interphalangeal joint extension between the injured and contralateral normal digit was defined as the radiographic lag difference. We randomized 87 subjects meeting the inclusion criteria to one of 3 splint types: volar padded aluminum splint, dorsal padded aluminum splint, and custom thermoplastic. Splints were continued for 6 weeks full-time. A total of 77 subjects were available for measurement of the primary outcome measure: radiographic lag difference at week 12. Secondary outcome measures were recorded at weeks 7 and 24. RESULTS: No lag difference was demonstrated at week 12 (p = .12), although a trend suggesting superiority (closest value to 0 difference) of the custom thermoplastic splint was observed. The mean radiographic lag differences were -16.2 degrees (95% confidence interval [CI], -21.3 degrees to 11.0 degrees ) for the dorsal padded aluminum splint, -13.6 degrees (95% CI, 18.0 degrees to -9.2 degrees ) for the volar padded aluminum splint, and -9.0 degrees (95% CI, -14.5 degrees to 3.4 degrees ) for the custom thermoplastic splint. Secondary between-group analyses showed no differences for radiographic or clinical lag, Michigan Hand Outcome Questionnaire scores, or complications. Secondary analyses of the whole cohort suggested that clinical measurement overestimates true lag, increased lag occurs after discontinuation of splinting, and clinically measured improvement in lag is noted at week 24. CONCLUSIONS: No lag difference was demonstrated between custom thermoplastic, dorsal padded aluminum splint, and volar padded aluminum splinting for Doyle I acute mallet fingers. Clinical measurement overestimates true lag in mallet injuries. Increased lag occurs after discontinuation of splinting. Increased age and complications correlate with worse radiographic lag. PMID- 20353860 TI - Custom-made splint treatment for osteoarthritis of the distal interphalangeal joints. AB - PURPOSE: We investigated the usefulness of a custom-made splint for treatment of painful osteoarthritis of the distal interphalangeal (DIP) joints. The splint was designed to be easily detachable so as not to diminish finger pad sensation or interfere with proximal interphalangeal joint motion. METHODS: We enrolled 25 patients (24 women and one man, mean age 58 y) with painful osteoarthritis of the DIP joints of the fingers and thumbs in this cohort study. Nineteen patients had multiple affected digits in one or both hands. Splints were applied to protect and immobilize the DIP joints. We assessed the outcome of this treatment using the visual analog scale pain score and the Quick Disabilities of the Arm, Shoulder, and Hand score for subjective assessment of symptoms. The mean follow up period after wearing the splint until assessment was 6 months. Subjects were assessed 6 months after they started wearing the splint. RESULTS: Pain decreased from 100% at pretreatment to 34% at final follow up. So, the average improvement ratio was 66%. The Quick Disabilities of the Arm, Shoulder, and Hand disability/symptom score changes were not statistically significant (28 points pretreatment and 17 points at final follow-up). CONCLUSIONS: This splint reduced pain from DIP osteoarthritis according to the visual analog scale; however, this does not enable the patient to obtain completely satisfactory function of the upper extremities. PMID- 20353861 TI - Morphometric analysis of potential osteochondral autografts for resurfacing unicondylar defects of the proximal phalanx in PIP joint injuries. AB - PURPOSE: This study was designed to morphometrically assess the base of the little and ring finger metacarpals as potential osteochondral donors to resurface distal condylar defects of the proximal phalanx. METHODS: The proximal phalanges were dissected from all 4 fingers in 10 cadaveric hands and the following measurements were obtained from the distal condylar surface: anteroposterior height, radial-ulnar width, and radius of curvature. Measurements were obtained from posteroanterior and lateral radiographic views, which were digitized and analyzed using digital imaging software. Comparable measurements were obtained from the base of the small and ring metacarpals. RESULTS: The anteroposterior dimension of both potential donor metacarpals was large enough to resurface the distal condyles of each of the proximal phalanges; however, this was not true for the radial-ulnar dimensions. The distal ulnar condyle of the long finger proximal phalanx was largest, measuring 4.9 (+/- 0.) mm dorsally and 6.2 (+/- 0.5) mm volarly in the radial-ulnar dimension. Only the small metacarpal base had sufficient stock in the radial-ulnar dimension (9.4 [+/- 1.7]) mm dorsally and 10.6 [+/- 2.0] mm volarly) to resurface this condyle. With respect to radius of curvature (ROC), the donor-to-recipient ROC ratio was 1.43 for the small metacarpal base versus 2.12 for the ring metacarpal base. Linear regression analysis revealed a stronger relationship in ROC between donor and recipient condyle when the small metacarpal base served as the donor (R = 0.96 vs R = 0.60). CONCLUSIONS: As determined from morphometric measurements of the 2 potential donor sites tested, the base of the small metacarpal provides the best match for resurfacing distal condylar defects of the proximal phalanges. PMID- 20353856 TI - [Pandemic influenza A (H1N1)v in the intensive care unit: what have we learned?]. AB - The characteristics of pandemic influenza 2009 differ from those of seasonal influenza. In Australia-New Zealand the number of admissions to the intensive care unit (ICU) increased by 15-fold in the southern winter. We compared the characteristics of the Spanish series of the first ICU admissions in July with those of series published in Canada and Australia-New Zealand up to October 2009. Unlike the situation in Spain, only half the admissions in Canada and Australia New Zealand were due to primary viral pneumonia but bacterial pneumonia was much more frequent. In all series, young people, many of whom had no comorbidities, were the most frequently affected population. The most common comorbidities were obesity, chronic pulmonary disease, pregnancy and heart disease. Diagnosis through reverse-transcriptase polymerase chain reaction can have a false-negative rate of 10%. Shock and acute renal insufficiency were more frequent in the Spanish series. A total of 10-30% of patients required ICU admission and 6 of 10 patients required mechanical ventilation with a high frequency of failure of non invasive ventilation (75%). Mortality was similar among the series (14-25%) but was higher in patients requiring mechanical ventilation (30%). Early oseltamivir administration (< 48h after symptom onset) has been associated with better outcome. Therefore, early administration of this drug in patients with risk factors or those who, although free from risk factors, show clinical progression, could reduce ICU admissions and mortality. PMID- 20353862 TI - Biomechanical comparison of dorsal nail plate versus screw and K-wire construct for extra-articular distal radius fractures in a cadaver bone model. AB - PURPOSE: The purpose of the study was to compare the biomechanical stability of distal radius fracture fixation with 2 new implants, the DNP (Hand Innovations LLC, Miami, FL), a dorsal locked hybrid of nail and plate, and the XSCREW (Zimmer, Freiburg, Germany), an implant combining a cannulated screw and K-wires, in a cadaver bone distal radius fracture model. METHODS: Eight pairs of fresh frozen cadaver radii were used. To simulate an extra-articular distal radius fracture, a 5-mm volar open wedge osteotomy was made. Axial loads of 10 to 100 N and torque loads of -1.5 to 1.5 Nm were applied by a testing machine to the intact radii and to the radii after each device was fixed as recommended by the manufacturer. One thousand cycles in torque and failure tests were performed. RESULTS: With a median of 136.0 N/mm, the axial stiffness of XSCREW-fixed specimens was higher than that of DNP-fixed specimens, with a median of 69.5 N/mm, but differences were not statistically significant. With a median of 0.163 Nm/ degrees , the torque stiffness of XSCREW-fixed specimens was significantly higher than that of DNP-fixed specimens, with a median of 0.068 Nm/ degrees . The XSCREW-group reached 33% of the axial stiffness and 49% of the torque stiffness of the intact radii, and the DNP-group reached 14% of the axial stiffness and 20% of the torque stiffness of the intact radii. CONCLUSIONS: In this human cadaver bone biomechanical study, the XSCREW provided more stability than the DNP in torque stiffness but not in axial stiffness. PMID- 20353863 TI - Wrist tendon forces during various dynamic wrist motions. AB - PURPOSE: A common treatment of arthritis of the thumb carpometacarpal joint requires all or a portion of the flexor carpi radialis tendon (FCR) to be used as an interpositional graft. The purpose of this study was to examine the in vitro tendon forces in 6 wrist flexors and extensors to determine whether their force contribution changes during various dynamic wrist motions along with a specific application to the FCR. METHODS: We tested 62 fresh-frozen cadaver wrists in a wrist joint motion simulator. During wrist flexion-extension, radioulnar deviation, dart throwing, and circumduction motions, the peak and average tendon forces were determined for the extensor carpi ulnaris, extensor carpi radialis brevis and longus, abductor pollicis longus, flexor carpi radialis, and flexor carpi ulnaris. RESULTS: During a dart-throwing motion, the mean and peak FCR forces were statistically less than during the other 3 motions. Conversely, the mean and peak flexor carpi ulnaris forces were statistically greater during the dart-throwing motion than during the other 3 motions. CONCLUSIONS: Patients who have undergone a surgical procedure in which all or a portion of the FCR has been harvested may experience a decrease in wrist strength with wrist motion, as the FCR tendon normally applies force during wrist motion. The motion least likely to be affected by such surgery is the dart-throwing motion when the force on the remaining FCR is minimized. PMID- 20353864 TI - Nonvascularized toe phalangeal transfer and distraction lengthening for symbrachydactyly. AB - Symbrachydactyly describes a spectrum of congenital hand differences consisting of digital loss resulting in fused short fingers. As the principles for distraction lengthening have evolved, the technique of nonvascularized toe phalangeal transfer to the hand with shortened digits has provided patients with improved outcomes. Nonvascularized toe phalanx to hand transplant with distraction lengthening restores functional length to a skeletally deficient, poorly functioning hand while maintaining an overlying layer of vascular and sensate tissue. The primary goal is improvement of digital length to enhance mechanical advantage and prehension. We describe the technique of nonvascularized toe phalangeal transfer and distraction lengthening for symbrachydactyly, including the following steps: nonvascularized proximal toe phalanx harvest, toe phalanx transfer to hand, pin placement, osteotomy, and closure. PMID- 20353865 TI - Reverse homodigital dorsoradial flap for thumb soft tissue reconstruction: surgical technique. AB - A variety of local flaps are described for reconstruction of soft tissue defects of the thumb. Restored sensibility, low donor-site morbidity, full restoration of function and range of motion, and an acceptable aesthetic outcome are requirements in thumb reconstruction. Reverse homodigital dorsal radial flap of the thumb provides most of these requirements and allows for dependable coverage of radiopalmar or dorsal thumb defects without affecting other digits. PMID- 20353866 TI - Current concepts of the treatment of adult brachial plexus injuries. AB - As the number of survivors of motor vehicle accidents and extreme sporting accidents increases, the number of people having to live with brachial plexus injuries increases. Although the injured limb will never return to normal, an improved understanding of the pathophysiology of nerve injury and repair, as well as advances in microsurgical techniques, have enabled the upper extremity reconstructive surgeon an opportunity to improve function in these life-altering injuries. The purpose of this review is to detail some of the current concepts of the treatment of adult brachial plexus injuries and give the reader an understanding of the nuances of the timing, available treatment options, and outcomes of treatment. PMID- 20353867 TI - Proprioception of the wrist following posterior interosseous sensory neurectomy. PMID- 20353869 TI - Molecular events of cellular apoptosis and proliferation in the early tendon healing period. PMID- 20353872 TI - Mallet finger injuries. PMID- 20353873 TI - Emergence of a novel and highly divergent HTLV-3 in a primate hunter in Cameroon. AB - The recent discovery of human T-lymphotropic virus type 3 (HTLV-3) in Cameroon highlights the importance of expanded surveillance to better understand the prevalence and public health impact of this new retrovirus. HTLV diversity was investigated in 408 persons in rural Cameroon who reported simian exposures. Plasma from 29 persons (7.2%) had reactive serology. HTLV tax sequences were detected in 3 persons. Phylogenetic analysis confirmed HTLV-1 infection in two individuals and HTLV-3 infection in a third person (Cam2013AB). The complete proviral genome from Cam2013AB shared 98% identity and clustered tightly in distinct lineage with simian T-lymphotropic virus type 3 (STLV-3) subtype D recently identified in two guenon monkeys near this person's village. These results document a fourth HTLV-3 infection with a new and highly divergent strain we designate HTLV-3 (Cam2013AB) subtype D demonstrating the existence of a broad HTLV-3 diversity likely originating from multiple zoonotic transmissions of divergent STLV-3. PMID- 20353874 TI - Release of TEGDMA from composite during the chewing situation. AB - The aim of this study was to investigate the triethylene glycol (TEGDMA) elution kinetics from light-cured composite with and without chewing simulation over a time period of 86 h. An experimental composite with TEGDMA labeled with a tracer dose of 14C-TEGDMA was used. The material parameters were in the range of commercially available composites. The mastification was simulated with the Fatigue-machine and the MUC-3 chewing simulator. 14C was eluted to 2.55% of the applied 14C-TEGDMA dose within 86 h after chewing simulation with the Fatigue machine and to 2.60% after chewing simulation with the MUC-3. Similar 14C-kinetic data were found for 14C-elution with and without chewing simulation with the Fatigue-machine and with MUC-3. During the first 26 h after the beginning of the experiments a linear 14C-elution kinetic was observed, followed by a second linear 14C-elution kinetic with a lower slope up to 86 h in both apparatus. It could be shown that chewing simulation has no significant (p<0.05) effect on the release of 14C-TEGDMA (and/or 14C-degradation products) from polymerized composites. PMID- 20353875 TI - Percentage of smudge cells determined on routine blood smears is a novel prognostic factor in chronic lymphocytic leukemia. AB - Recently developed molecular prognostic tests in patients with early Binet stage chronic lymphocytic leukemia (B-CLL) are costly and often require a high level of technologic expertise. Recent data give evidence for the prognostic relevance of the percentage of smudge cells in B-CLL. In our study we analysed the prognostic potential of this novel marker in a cohort of 100 CLL patients. The percentage of smudge cells ranged from 0% to 70% (median 21%). Patients with 20% smudge cells. Multivariate Cox regression analysis identified percentages of smudge cells, stage according to Binet and CD38 expression as independent prognostic markers. The percentage of smudge cells was significantly lower in CD38+, ZAP-70+ and unmutated IgVH patients. Combined analysis of smudge cell percentages with CD38 expression provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Comparing gene expression profiles in a subset of 12 patients we identified eight differentially expressed genes in groups with high vs. low percentage of smudge cells suggesting a role of these differentially expressed genes, especially for Tribbles homolog 2 (Trib2), in the disease progression of high risk CLL patients. In conclusion, our data confirm previous studies showing that the simple and inexpensive microscopic detection of smudge cells on blood smears prepared for routine diagnostic purposes is a novel independent factor predicting overall survival in CLL. PMID- 20353876 TI - Prolonged endoplasmic reticulum stress promotes mislocalization of immunoglobulins to the cytoplasm. AB - Signal peptide-dependent insertion of newly synthesized proteins into the endoplasmic reticulum (ER) is a multi-step process, whose fidelity varies with the identity of the protein and the cell type. ER translocation of prions is sensitive to conditions of acute ER stress in a manner that pre-emptively prevents their aggregation and proteo-toxicity. While this has been documented for extreme ER stress conditions and for a special type of proteins, the impact of chronic ER stress on protein translocation in general has not been well characterized. The unfolded protein response (UPR) is a cytoprotective signaling pathway activated by ER stress. The transcription factor X-box-binding protein 1 (XBP-1) is a key element of the mammalian UPR, which is activated in response to ER stress. Deletion of XBP-1 generates constitutive chronic ER stress conditions. Chronic ER stress can also be produced pharmacologically, for example by prolonged treatment with proteasome inhibitors, which abrogates XBP-1 activation. We tested the impact of chronic ER stress on protein insertion into the ER with special emphasis on antibody secreting cells (ASCs), as these cells cope physiologically with prolonged stress conditions. We show that XBP-1 in plasmablasts and fibroblasts controls the ER translocation of US2, a viral encoded protein with a priori poor insertion efficiency. Using monoclonal antibodies that preferentially recognize ER-mis-inserted micro Ig chains we demonstrate that prolonged treatment of plasmablasts with proteasome inhibitors, as well as deletion of XBP-1, impaired the translocation of mu chains to the ER. Our data suggest that ASCs under prolonged ER stress conditions endure cytoplasmic mislocalization of Ig proteins. This mislocalization may further explain the exquisite sensitivity of multiple myeloma to proteasome inhibitors. PMID- 20353877 TI - Implication of discoidin domain receptor 1 in T cell migration in three dimensional collagen. AB - T cell migration through extracellular matrix of the tissue is an important process in the development of inflammation. However, the mechanisms regulating this process are complex and still not well defined. In this study, we show that activation of human peripheral blood T cells with anti-CD3 mAb increases the mRNA and protein levels of the discoidin domain receptor 1 (DDR1), which is known to bind to collagens. Furthermore, our findings indicate that DDR1 is involved in the migration of activated T cells in three-dimensional (3D) collagen. Indeed, the use of a DDR1 blocking molecule (DDR1:Fc) reduced the capacity of anti-CD3 activated human T cells to migrate in 3D collagen, whereas a control immunoglobulin had no effect. As a control, the DDR1:Fc molecule did not interfere with the capacity of human T cells to migrate through fibronectin. Together these results suggest that DDR1 can represent an additional receptor regulating T cell movement in the tissues and therefore can contribute to the development of inflammatory diseases. PMID- 20353878 TI - Left ventricular pseudoaneurysm and alpha1-antitrypsin enzyme deficiency: another pathological correlation. AB - Alpha1-antitrypsin deficiency (A1ATD) is usually linked to chronic lung dysfunction and chronic liver disease. Recent evidence have shown involvement also of the cardiovascular system. Indeed, dissection of the thoracic aorta or of the coronary arteries, and intra-cerebral aneurysms has been shown to represent concomitant vascular adverse events and apparently related to the impaired vascular wall integrity, strictly related to the elastase levels which are usually modulated by the A1AT. The case herein reported describes a patient affected by A1ATD associated with a large pseudoaneurysm of the left ventricle without any known predisposing factors to pseudoaneurysm development (coronary artery disease, acute myocardial infarction, taruma and myocarditis) indicating that the connective tissue impairment documented in A1ATD may also affect the myocardial structure, ultimately leading to weakened wall integrity, sudden rupture and pseudoaneurysm formation successfully managed by a surgical approach. PMID- 20353879 TI - Role of surgical resection for pulmonary metastasis of hepatocellular carcinoma. AB - INTRODUCTION: The lung is one of the most important organs affected by metastasis of hepatocellular carcinoma. However, pulmonary metastasectomy for hepatocellular carcinoma has not been well documented. The aim of this study was to evaluate long-term outcome after pulmonary metastasectomy due to metastasis of hepatocellular carcinoma. METHODS: Between January 1998 and December 2008, 41 patients underwent pulmonary metastasectomy. Retrospective reviews of medical records and telephone surveys were conducted to identify risk factors of long term survival. RESULTS: Median time between a complete remission of hepatocellular carcinoma and pulmonary metastasectomy was 11 (4-105) months. During median 25-month follow-up time after metastasectomy, hepatocellular carcinoma recurred in 33 patients. Overall survival rate was 66.9+/-10% in all 41 patients and disease free survival was 24.5+/-10% in 24 patients who had no viable hepatocellular carcinoma in the liver preoperatively. An analysis of recurrence revealed that survival was better in patients whose recurrence was limited to either in the liver or lungs compared to that in patients whose recurrence took place in the distant organ other than the liver or lungs (extrahepatic/extrapulmonary metastasis) (p=0.004, log-rank). CONCLUSIONS: Pulmonary metastasectomy for hepatocellular carcinoma can be performed safely without major morbidity. Recurrence at organs other than the liver or lung was found to result in poor survival, which suggests that a careful search for distant metastasis at other locations is mandatory for patient selection. This study demonstrated that pulmonary metastasectomy can play an important role in selected patients with pulmonary metastasis of hepatocellular carcinoma. PMID- 20353880 TI - Thermal stability investigation of sulfide minerals in DSC. AB - The safe mining of sulfide ores requires knowledge of the stability/reactivity of the ores under a variety of conditions. This is a large part due to the oxidative self-heating behavior of these ores. In this study, an advanced kinetic simulation approach was used to evaluate the oxidative self-heating of sulfide mineral concentrate. Kinetic parameters were determined on the basis of non isothermal DSC measurements at different heating rates by Friedman and ASTM-E698 methods. The estimated kinetic parameters were employed to predict reaction progress under different temperature regimes. The calculated and experimental isothermal profiles suggest an autocatalytic behavior for mineral concentrate oxidation. The precise prediction of reaction rates/progress by an advanced kinetic-based simulation approach in this study is critical from a safe storage and handling perspective. PMID- 20353881 TI - Impact of ultrasonication time on elution of super heavy oil and its biomarkers from aging soils using a Triton X-100 micellar solution. AB - An ultrasound-enhanced elution system with Triton X-100 solution was used to remediate aging soils contaminated with super heavy oil. We used GC/MS, SEM, and X-ray diffraction (XRD) to analyze the effect of ultrasonic time (0-1800 s) on the elution of super heavy oil and its three characteristic biomarkers (C(26-34) 17alpha 25-norhopanes, C(26-28) triaromatic steroid [TAS], and C(27-29) methyl triaromatic steroid [MTAS]). The oil and biomarkers remaining in the treated soils followed similar second-order functions with increasing ultrasonication times. Biomarker elution was closely related to carbon numbers in the marker. For C(26-34) 17alpha 25-norhopanes, the smaller molecules were more readily eluted during 0-360 s ultrasound. This trend was reversed upon application of ultrasound during 1080-1800 s, with improved elution of larger molecules and elution followed a similar second-order function. For C(26-28) TAS, smaller molecules were more readily eluted but the elution of larger molecules followed a similar second-order function. For C(27-29) MTAS, elution of larger molecules was close to that of C(26-34) 17alpha 25-norhopanes. Results of SEM and XRD indicated that the mineral and chemical compositions of soils eluted at ultrasonication times of 1080-1800 s closely resembled clean soils. PMID- 20353882 TI - Determination of trace copper in food samples by flame atomic absorption spectrometry after solid phase extraction on modified soybean hull. AB - Soybean hull was chemically modified with citric acid and used as a solid phase extraction adsorbent for the determination of trace amounts of Cu(2+) in food samples by flame absorption spectrometry (FAAS). The effect of pH, sample flow rate and volume, elution flow rate and volume and co-existing ions on the recovery of the analyte were investigated. The results showed that Cu(2+) could be adsorbed on the modified soybean hull at pH 8.0 and eluted by 2.0 mL of 1.0 mol L(-1) HCl. Under the optimized conditions, the adsorption capacity of modified soybean hull was found to be 18.0 mg g(-1) for Cu(2+). The detection limit of the proposed method was 0.8 ng mL(-1) for Cu(2+) with an enrichment factor of 18. The analytical result for the certified reference tea sample (GBW07605) was in a good agreement with the certified value. The proposed method has also been successfully applied to the determination of trace Cu(2+) in dried sweet potato, lake water and milk powder, the recovery of Cu(2+) for spiked samples was between 91% and 109.6%. PMID- 20353883 TI - Levels and patterns of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in municipal waste incinerator bottom ash in Zhejiang province, China. AB - Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were analyzed in bottom ash from municipal solid waste (MSW) incineration in six cities in Zhejiang province, where one-fourth of the MSW incinerators of China are located. Total PAH contents varied from 2222.53 to 6883.91 microg/kg. The patterns of PAHs were found to be very similar in all the samples, dominated by three-ring and four-ring PAHs. Total PCB concentrations in bottom ash ranged from 1.00 to 1.31 microg/kg, while the coplanar PCBs in the bottom ash were in the range of 0.08-0.52 microg/kg. Among PCB congeners, low chlorinated PCBs contributed to the majority of total PCBs. Generally, PAH concentrations in cities with fluidized bed incinerator were less than those in cities with grate furnace incinerator. PAH and PCB levels were affected by both plastic content in MSW incinerator feed and combustion efficiency. However, further study is required to investigate the effect of these two variables deeply, as well as other influencing factors. PMID- 20353884 TI - Prevalence and molecular mechanism of macrolide resistance in beta-haemolytic streptococci in The Netherlands. AB - The prevalence of resistance to erythromycin and clindamycin as well as the presence of the resistance genes mef(A), mef(E), erm(A) and erm(B) were determined in 1076 consecutive isolates of beta-haemolytic streptococci of Lancefield groups A (n=219), B (n=562),C (n=58) and G (n=237) collected during 2005 and 2006. The prevalence of macrolide resistance was highest in group C streptococci (6.9%), followed by group B (5.3%), group G (4.6%) and group A (1.4%). Eighty-eight percent of resistance was mediated by erm(A) and erm(B) genes. Macrolide resistance in beta-haemolytic streptococci in The Netherlands is low, but increasing macrolide resistance was observed in group B streptococci. PMID- 20353885 TI - Antidepressant-like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system. AB - The antidepressant-like effect of trans-resveratrol, a phenolic compound present in polygonum cuspidatum, was evaluated through behavioral and neurochemical methods. trans-Resveratrol (20, 40 and 80 mg/kg, via gavage) significantly decreased the immobility time in mouse models of despair tests, but did not influence locomotor activity. Two behavioral models and neurochemical assays suggested that trans-resveratrol produced a significant increase in serotonin and noradrenaline levels at 40 or 80 mg/kg in brain regions. In addition, trans resveratrol dose dependently inhibited MAO-A activity. These findings indicate that the antidepressant-like effect of trans-resveratrol might be related to serotonergic and noradrenergic activation. PMID- 20353886 TI - Development and analytical application of a glucose biosensor based on glucose oxidase/O-(2-hydroxyl)propyl-3-trimethylammonium chitosan chloride nanoparticle immobilized onion inner epidermis. AB - A glucose biosensor comprising a glucose oxidase/O-(2-hydroxyl)propyl-3 trimethylammonium chitosan chloride nanoparticle (O-HTCC NP)-immobilized onion inner membrane and a dissolved oxygen (O(2)) sensor has been successfully developed. The detection scheme is based on the depletion of dissolved O(2) content upon exposure to glucose. The decrease in O(2) level was monitored and related to the glucose concentration. The biosensor shows linear response to glucose from 0.0 to 0.60 mM with a detection limit of 50 microM (S/N=3). The effect of O-HTCC NP and enzyme loading, pH, temperature, and phosphate buffer concentration on the sensitivity of the biosensor was studied in detail. The biosensor exhibits fast response time (70s), good repeatability (3.2%, n=10) and storage stability (90% of initial sensitivity after 3-week storage). Common interferents including acetic acid, lactic acid, propionic acid, butyric acid, folic acid, methanol, glycine, DL-alpha-alanine and DL-cysteine do not cause significant interferences on the biosensor. The proposed biosensor method was successfully applied to determine the glucose content in real samples such as orange juice, red wine and tea drink and the results were comparable to that obtained from a spectrophotometric method. The glucose recovery test demonstrates that the proposed glucose biosensor offers an excellent, accurate and precise method for the determination of glucose in real samples. PMID- 20353887 TI - Multilayer silver nanoparticles-modified optical fiber tip for high performance SERS remote sensing. AB - This work presents the construction and optimization of nanoparticles-modified optical fiber tip (NPs-MOFT) devices for remote sensing by surface-enhanced Raman scattering (SERS). Silver nanoparticles (Ag-NPs) were self-assembled on optical fiber tips through a "layer-by-layer" procedure. It is shown that the SERS performance is at optimum when 5 "layers" of 50 nm Ag-NPs were deposited on the optical fiber tip. Using the optimized Ag-NPs-MOFT device, it was possible to detect 200 nM of the R6G dye in remote sensing mode (backscattering through the fiber). It was also possible to detect dye molecules with different structures and charges at the micro-molar concentration level, including anions, cations and neutral species. It can be envisioned that the Ag-NPs-MOFT device reported in this work can be further developed for SERS-based remote biosensing. PMID- 20353888 TI - Electrochemical biosensor for estrogenic substance using lipid bilayers modified by Au nanoparticles. AB - There is a growing demand for new technologies that are capable of screening the wide variety of xenoestrogens in environment. Here, a nanostructure electrochemical biosensor was developed to directly detect and screen estrogenic substances based on estrogen receptor (ER) binding without the use of radio- or enzyme-labeled compounds. The biosensor was fabricated by immobilization of ERs in supported bilayer lipid membrane (s-BLM) modified with Au nanoparticles, and the properties of the modified electrodes were characterized by cyclic voltammetry and impedance spectroscopy. The results indicated that the biosensor was able to detect the natural estrogen 17beta-estradiol with an acceptable linear correlation ranging from 5 to 150 ng/L and a detection limit of 1 ng/L. The biosensor could also detect other known xenoestrogens such as bisphenol A and 4-nonylphenol with satisfied sensitivity and quantitative results. The biosensor showed good reliability and repeatability, and the Au nanoparticles greatly enhanced the sensitivity and stability of the biosensor. Moreover, estrogenic activity of water samples determined by this biosensor was in good agreement with that determined by MCF-7 cell proliferation assay. PMID- 20353889 TI - Nanogold-enwrapped graphene nanocomposites as trace labels for sensitivity enhancement of electrochemical immunosensors in clinical immunoassays: Carcinoembryonic antigen as a model. AB - A new, highly sensitive electrochemical immunosensor with a sandwich-type immunoassay format was designed to quantify carcinoembryonic antigen (CEA), as a model tumor marker, using nanogold-enwrapped graphene nanocomposites (NGGNs) as trace labels in clinical immunoassays. The device consisted of a glassy carbon electrode coated with Prussian Blue (PB) on whose surface gold nanoparticles were electrochemically deposited to the further modified with the specific analyte capturing molecule, anti-CEA antibodies. The immunoassay was performed using horseradish peroxidase (HRP)-conjugated anti-CEA as secondary antibodies attached on the NGGN surface (HRP-anti-CEA-NGGN). The method using HRP-anti-CEA-NGGNs as detection antibodies shows high signal amplification, and exhibits a dynamic working range of 0.05-350 ng/mL with a low detection limit of 0.01 ng/mL CEA (at 3s). The assayed results of serum samples with the sensor received an acceptable agreement with the reference values. Importantly, the methodology provides a promising ultrasensitive assay strategy for clinical applications. PMID- 20353890 TI - Preparation of a novel colorimetric luminescence sensor strip for the detection of indole-3-acetic acid. AB - A novel colorimetric luminescence sensor strip for the detection of indole-3 acetic acid (IAA) has been fabricated by using green emissive quantum dots of cadmium telluride (CdTe QDs) as a background layer and a red emissive europium chelate, [4'-(9-anthryl)-2,2':6',2''-terpyridine-6,6''-diyl]bis(methylenenitrilo) tetrakis(acetate)-Eu(3+) (ATTA-Eu(3+)), as a specific sensing layer coated on the surface of glass slide, respectively. The luminescence response of the sensor strip is given by the dramatic changes in emission colors from green to red at different IAA concentrations. This approach provides a simple, rapid, sensitive and accurate method for the detection of IAA without using any special scientific instruments. PMID- 20353891 TI - Synovial hemangioma of the ankle. AB - Synovial hemangioma is a rare benign vascular tumor that arises from any synovium lined surface. The most typical form is the intra articular type in which the tumor forms a mass lined by synovial membrane. We report a case of a juxta articular synovial hemangioma of the ankle. PMID- 20353892 TI - Preservation of the pulmonary autograft after failure of the Ross procedure. AB - OBJECTIVE: Failure of the pulmonary autograft following the Ross Procedure is mainly due to dilatation and/or cusp prolapse causing insufficiency. We analysed the result of pulmonary autograft valve sparing and repair, using techniques developed for native aortic root and valve. METHODS: Of a total of 275 patients who underwent Ross operation between 1991 and 2009, 31 needed autograft re operation. Of the 28 patients re-operated in our centre, 26 (93%) had autograft valve preservation and they represent the study cohort. At the initial Ross procedure, root remplacement technique was performed in 20 patients and autograft inclusion technique was performed in 6. Mean redo interval was 9.3 + or - 3.5 years and mean age at redo was 44 + or - 13 years. Indications for re-operations were neo-aorta dilatation (n=12; 46%), autograft insufficiency (n=4; 15%) and dilatation with autograft insufficiency (n=10; 40%). Neo-aorta dilatation was repaired using valve-sparing root replacement (n=12, 46%) or ascending aorta replacement (n=10; 40%). Cusp prolapse was repaired by commissural re-suspension (n=1), free margin plication (n=10) or re-suspension with polytetrafluoroethylene (PTFE; n=6). Cusp repair was performed in isolation (n=4) or in association with sparing (n=5) or ascending aorta replacement (n=4). RESULTS: There was no in hospital mortality. Two patients having undergone isolated cusp repair needed valve replacement for recurrent insufficiency after 5 days and 8 years postoperatively. At follow-up (100% complete, median: 27 months) all patients were alive, in New York Heart Association (NYHA) class I (n=22; 84%) or II (n=4; 16%). No autograft regurgitation was present in nine patients (five sparing and four ascending aorta replacement); grade I insufficiency was present in 11 (six sparing and five ascending aorta replacement), grade 2 in two (one sparing and one isolated cusp repair) and grade 3 in two (one ascending aorta replacement and one isolated cusp repair). At 3 years, overall freedom from autograft insufficiency > or = grade 3 was 80%. CONCLUSION: Preservation of the pulmonary autograft valve can be safely performed in selected patients. At midterm, repair of neo-aorta dilatation using valve-sparing root replacement or ascending aorta replacement showed acceptable results. In contrast, results of cusp repair for isolated autograft insufficiency were unsatisfactory. PMID- 20353893 TI - Concordance between epidermal growth factor receptor status in primary non-small cell lung cancer and metastases: a post-mortem study. AB - OBJECTIVES: Epidermal growth factor receptor (EGFR)-targeted therapies are a valid therapeutic option for advanced non-small-cell lung cancer (NSCLC), but unequivocally recognised predictive factors for therapeutic response are lacking. However, intrinsic resistance might occur due to loss of EGFR expression during the course of the disease or its treatment. METHODS: Paraffin-embedded tissue from cases with metastatic NSCLC obtained at autopsy was retrieved from our archive. Specimens of primary tumour (n=39; 64% adenocarcinoma) and of all corresponding metastases (n=70) were immunohistochemically stained for EGFR expression. Two observers independently scored staining intensity and evaluated the percentage of positively stained cells. Identical staining intensity and < or = 10% difference in number of stained cells were defined as perfect concordance; and one-increment difference in staining intensity and less than 30% difference in number of stained cells were defined as good concordance. RESULTS: Twenty seven out of 39 primary tumours (69%) were EGFR-positive on immunohistochemistry (IHC), with 12/27 (44%) of positive tumours exhibiting intense or moderate EGFR expression. The median number of EGFR-expressing cells in primary tumours was 50% (range 0-100%). Overall Spearman's rank correlations for staining intensity and percentage of positively stained cells between primary tumours and paired metastases were 0.78 (p<0.001) and 0.60 (p<0.001), respectively. Perfect concordance was observed in 51% (20/39) and good concordance in 18% (7/39) of corresponding pairs, respectively, whereas 9/12 metastases showing discordant staining with their corresponding primary tumours had lacked EGFR expression. CONCLUSIONS: In most NSCLCs, EGFR status of primary tumours correlates with EGFR status of corresponding metastases. Hence, loss of EGFR expression is unlikely during disease progression, local or non-EGFR-targeting systemic treatment. PMID- 20353894 TI - Growth of the lateral tunnel in patients who underwent a total cavopulmonary connection at less than 5 years of age. AB - OBJECTIVE: A lateral tunnel-total cavopulmonary connection (LT-TCPC) using a right atrial (RA) free wall is the first choice of treatment for patients with a small body weight in this institute. Whether the growth of the LT is appropriate or not according to the growth of the body remains controversial. In addition, the optimal initial diameter of an LT is unknown. The purpose of this study was to verify the growth of the LT. METHODS: Ninety-one patients of a total of 267 TCPC cases underwent an LT-TCPC at less than 5 years of age in this institute between March 1991 and June 2008. The data on 47 of the 91 patients, which were available to investigate the LT growth, were retrospectively reviewed. The mean age at LT-TCPC was 37+/-11 months (16-57 months). The mean body weight at TCPC was 12.4+/-2.4 kg (7.6-20.0 kg). The initial LT diameter was determined with Hegar's sizer of the estimated half-pulmonary arterial (PA) diameter, which is a diameter that results in half of the dimension of the normal pulmonary valve. The measured maximum LT diameter (mm) divided by the estimated half-PA diameter (mm) was considered as the LT index. The size of the LT was evaluated using either echocardiography or angiography. RESULTS: The mean follow-up period was 7.4+/-3.5 years (1.6-13.5 years). The LT index was initially 2.0+/-0.7 (1.3-4.5), 2.0+/-0.4 (1.3-3.2) at 1 year after operation, 2.1+/-0.5 (1.5-3.2) at 5 years after operation, 1.9+/-0.4 (1.5-2.8) at 10 years after operation and 2.1+/-0.5 (1.6 2.5) at 13 years after operation, respectively. CONCLUSIONS: LT growth suitable for the body growth can be expected. Although there was some variation in the initial LT diameter, the LT index tended to converge at 2.0 with growth. PMID- 20353895 TI - Intra-operative sentinel lymph node identification using a novel receptor-binding agent (technetium-99m neomannosyl human serum albumin, 99mTc-MSA) in stage I non small cell lung cancer. AB - OBJECTIVE: In the previous report, to simplify the synthesis and labelling procedures and to improve the biological properties, we developed a novel mannose receptor-binding agent, technetium-99m human serum albumin (99mTc-MSA), for sentinel lymph node detection. This study is the first clinical trial designed to test the reliability and feasibility of sentinel node detection using this new radioactive agent in patients with stage I non-small cell lung cancer. METHODS: Forty-two patients (30 men, 12 women; mean age 63.3 + or - 8.9 years) that were candidates for lobectomy with mediastinal lymph node dissection for stage I non small cell lung cancer were enrolled. A total dose of 1mCi of 99mTc-MSA in 0.2 ml was administered in one shot at the peritumoural region approximately 3h before surgery. The radioactivity in the lymph nodes was counted before (in vivo) and after (ex vivo) dissection with a hand-held gamma probe. A sentinel lymph node was defined as any node for which the radioactivity count was 5 times that of the resected lung tissue with the lowest count for the ex vivo counts. All harvested lymph nodes were cut into 2-mm slices and ultimately diagnosed by using formalin fixed and paraffin-embedded sections with haematoxylin and eosin staining. RESULTS: 99mTc-MSA was taken up by the lymph nodes and its detection did not change until 21 h after the injection. The number of dissected lymph nodes per patient was 22.1 + or - 11.6 (range 4-57). Among 42 patients, the sentinel lymph nodes could be identified in 40 patients (95.2%). The number of sentinel lymph nodes identified was 2.3 + or - 1.1 stations (range 1-5) per patient. Ten out of 40 patients (25.0%) had metastases in 11 sentinel lymph nodes. Three of these 11 sentinel lymph nodes (27.3%) had skip metastases. No false-negative sentinel lymph nodes were detected in any of the 10 patients with N1 or N2 disease (0%). The relationship between in vivo and ex vivo results for mediastinal sentinel lymph nodes showed concurrence in 29 out of 40 patients (72.5%). CONCLUSIONS: Intra-operative sentinel lymph node identification using 99mTc-MSA appears to be feasible and reliable in stage I non-small cell lung cancer. PMID- 20353897 TI - Development of a cancer-specific Comprehensive Geriatric Assessment in a University Hospital in Spain. AB - INTRODUCTION: The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients. The goals of the current study were to develop a brief but non-self-administered cancer-specific geriatric assessment and to determine its feasibility, as measured by (1) the length of time to completion and (2) patient satisfaction. METHODS: The literature was reviewed to select validated scales for geriatric assessment across the following domains: functional status, co-morbidity, cognition, social support and risk of malnutrition. Oncologic patients older than 70 years were included in the study. RESULTS: The instrument was completed by 99 patients (mean age, 78.65 yrs). The mean time to completion of that was 12.9 min (range, 9.5-20.5 min). Most patients were satisfied with its length (63.6%), and most considered it fairly easy to complete (69.7%). CONCLUSIONS: The designed CGA was accepted by most patients and was not perceived to be overly time-consuming. PMID- 20353896 TI - Surgery for complications of trans-catheter closure of atrial septal defects: a multi-institutional study from the European Congenital Heart Surgeons Association. AB - OBJECTIVE: This study aims to analyse the collective experience of participating European Congenital Heart Surgeons Association centres in the surgical management of complications resulting from trans-catheter closure of atrial septal defects (ASDs). METHODS: The records of all (n=56) patients, aged 3-70 years (median 18 years), who underwent surgery for complications of trans-catheter ASD closure in 19 participating institutions over a 10-year period (1997-2007) were retrospectively reviewed. Risk factors for surgical complications were sought. Surgical outcomes were compared with those reported for primary surgical ASD closure in the European Association of Cardio-thoracic Surgery Congenital Database. RESULTS: A wide range of ASD sizes (5-34mm) and devices of various types and sizes (range 12-60mm) were involved, including 13 devices less than 20mm. Complications leading to surgery included embolisation (n=29), thrombosis/thrombo-embolism/cerebral ischaemia or stroke (n=12), significant residual shunt (n=12), aortic or atrial perforation or erosion (n=9), haemopericardium with tamponade (n=5), aortic or mitral valve injury (n=2) and endocarditis (n=1). Surgery (39 early emergent and 17 late operations) involved device removal, repair of damaged structures and ASD closure. Late operations were needed 12 days to 8 years (median 3 years) after device implantation. There were three hospital deaths (mortality 5.4%). During the same time period, mortality for all 4453 surgical ASD closures reported in the European Association of Cardio-Thoracic Surgery Congenital Database was 0.36% (p=0.001). CONCLUSIONS: Trans-catheter device closure of ASDs, even in cases when small devices are used, can lead to significant complications requiring surgical intervention. Once a complication leading to surgery occurs, mortality is significantly greater than that of primary surgical ASD closure. Major complications can occur late after device placement. Therefore, lifelong follow-up of patients in whom ASDs have been closed by devices is mandatory. PMID- 20353898 TI - Right atrial pacing for prevention of postoperative atrial fibrillation following coronary artery bypass grafting: a prospective observational trial. AB - INTRODUCTION: Atrial fibrillation (AF) is the most common complication after coronary artery bypass grafting (CABG). Conventional clinical practice is to treat AF after its onset in the postoperative period. However effective prophylaxis can result in reduced morbidity and hospital stay. This prospective study was designed to assess the efficacy of right atrial pacing in the prevention of postoperative AF following CABG. METHODS: All patients who had isolated first time CABG on cardiopulmonary bypass between January 2007 and June 2007, operated by one surgeon were included in this study (study group). During the same period, isolated CABG carried out by other surgeons in the same unit and not paced served as control (control group). In the study group (n=24) right atrial pacing was continued for 96h in the postoperative period. The end points of the study were occurrence of AF, death in postoperative period or discharge from hospital. RESULTS: In the study group 5 patients could not be paced because of persistent tachycardia or failure of atrial electrodes. There was a statistically significant reduction in the incidence of postoperative atrial fibrillation from 31.1% in control group to 5.2% (p-value 0.03) in patients who were paced. CONCLUSIONS: The preliminary results of this study suggest that prophylactic right atrial pacing significantly reduced the incidence of AF following CABG. However these results need to be confirmed in a larger cohort of patients in a prospective randomised trial. PMID- 20353900 TI - [Evacuation plan of an intensive care unit: a new quality indicator?]. AB - The intensive care units must be prepared for a possible disaster, whether internal or external, in case it becomes necessary to evacuate the in-patients. They must have an Emergency and Self-protection Plan that includes the patient evacuation criteria and this must be known by all the personnel who work in the service. For that reason, the patients must be triaged, based on their attention priorities, according to their survival possibilities. Having an evacuation, known by all the personnel and updated by means of the performance of periodic drills, should be included as a quality indicator that must be met, since this would achieve better attention to the patient in case of a disaster situation requiring the evacuation of the ICU. PMID- 20353899 TI - Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: finding the right balance in response to danger signals. AB - INTRODUCTION: Interleukin-1 was the first cytokine identified and is a powerful inducer of fever and inflammation. The biologically active receptor for IL-1, shares signaling pathways with some pathogen recognition receptors, the Toll-like receptors (TLRs) which early on suggested an important role in innate immune function. DISCUSSION: The discovery that some intracellular "danger receptors", the NOD like receptors (NLRs) can assemble to form multimolecular platforms, the inflammasomes, that not only sense intracellular danger but also activate IL 1beta, has provided the molecular basis for the integration of IL-1 as an early response mediator in danger recognition. The critical role of balancing IL-1 production and signaling in human disease has recently been demonstrated in rare human monogenic diseases with mutations that affect the meticulous control of IL 1 production, release and signaling by leading to decreased or increased TLR/IL-1 signaling. In diseases of decreased TLR/IL-1 signaling (IRAK-4 and MyD88 deficiencies) patients are at risk for infections with gram positive organisms; and in diseases of increased signaling, patients develop systemic autoinflammatory diseases (cryopyrin-associated periodic syndromes (CAPS), and deficiency of the IL-1 receptor antagonist (DIRA)). CONCLUSION: Monogenic defects in a number of rare diseases that affect the balance of TLR/IL-1 signaling have provided us with opportunities to study the systemic effects of IL-1 in human diseases. The molecular defects in CAPS and DIRA provided a therapeutic rationale for targeting IL-1 and the impressive clinical results from IL-1 blocking therapies have undoubtedly confirmed the pivotal role of IL-1 in human disease and spurred the exploration of modifying IL-1 signaling in a number of genetically complex common human diseases. PMID- 20353901 TI - [The current role of the Swan-Ganz catheter]. AB - Nearly forty years ago, Swan and Ganz introduced pulmonary artery catheterization to monitor the hemodynamic status of critical patients. The need for pulmonary artery catheterization in clinical practice has been questioned because it may be related to increased mortality and because alternative techniques that will probably cause less morbidity and mortality have been developed. The introduction of color Doppler echocardiography has been fundamental in the hemodynamic and etiologic evaluation of critical patients and has made it possible to clarify many clinical situations in which the response to treatment was unacceptable. This review aims to discuss the advantages and drawbacks of the Swan-Ganz catheter as the gold standard for monitoring hemodynamics in critical patients. We believe that combining the available techniques should help us evaluate the hemodynamics in critical patients and determine the cause of hemodynamic instability so we can select the most appropriate initial treatment and evaluate the subsequent response. PMID- 20353902 TI - [Subcapsular hepatic hematoma after ERCP]. PMID- 20353903 TI - Magnesium and cardiovascular system. AB - Hypomagnesemia is common in hospitalized patients, especially in the elderly with coronary artery disease (CAD) and/or those with chronic heart failure. Hypomagnesemia is associated with an increased incidence of diabetes mellitus, metabolic syndrome, mortality rate from CAD and all causes. Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function, including platelet aggregation and adhesion, which potentially gives magnesium physiologic and natural effects similar to adenosine-diphosphate inhibitors such as clopidogrel. The data regarding its use in patients with acute myocardial infarction (AMI) is conflicting. Although some previous, relatively small randomized clinical trials demonstrated a remarkable reduction in mortality when administered to relatively high risk AMI patients, two recently published large scale randomized clinical trials (the Fourth International Study of Infarct Survival and Magnesium in Coronaries) failed to show any advantage of intravenous magnesium over placebo. Nevertheless, there are theoretical potential benefits of magnesium supplementation as a cardioprotective agent in CAD patients, as well as promising results from previous work in animal and humans. These studies are cost effective, easy to handle and are relatively free of adverse effects, which gives magnesium a role in treating CAD patients, especially high-risk groups such as CAD patients with heart failure, the elderly and hospitalized patients with hypomagnesemia. Furthermore, magnesium therapy is indicated in life-threatening ventricular arrhythmias such as Torsades de Pointes and intractable ventricular tachycardia. PMID- 20353904 TI - Folliculostellate cells in pituitary pars distalis of male viscacha: immunohistochemical, morphometric and ultrastructural study. AB - Folliculostellate cells (FSC) have been reported in pituitary of several mammalian species. FSC morphology and secreted substances have been instrumental to the understanding of their function. The purpose of this work was to perform an immunohistochemical, morphometric and ultrastructural study of the pituitary pars distalis FSC in adult male viscacha and to analyze their relation with hormone secreting cells. Immunohistoche-mistry and image analysis were carried out in different sectors of the gland, from the middle (sector 1) to the glandular periphery (sector 5). Transmission electron microscopy with lanthanum as electrodense tracer was used. FSC formed follicles with PAS-positive colloid inside. They expressed S-100 protein mainly in both nucleus and cytoplasm. FSC were stellate-like in shape and exhibited short cytoplasmic processes that contacted with blood vessels and endocrine cells. In addition, some follicular colloids were immunostained with anti-S-100 protein. A few FSC were immunostained with anti-glial fibrillary acidic protein (GFAP) and anti-vimentin. The morphometric parameters analyzed (percentages of S-100-positive total, cellular and colloidal areas) increased from sector 1 to sector 3 and then decreased to sector 5. Hormone secreting cells, mainly lactotrophs, gonadotrophs and corticotrophs were associated with FSC and follicles. The ultrastructural study demonstrated that FSC developed junctional complexes and desmosomes between their lateral membranes. Lanthanum freely penetrated the spaces between granulated cells and FSC, but did not penetrate into the follicular lumen. IN CONCLUSION: 1) the differential expression of S-100 protein, GFAP and vimentin may indicate different physiological stages of FSC; 2) the expression of these proteins suggests a neuroectodermic origin of these cells; 3) FSC spatial distribution, association with endocrine cells, and the generation of an intercellular communication network suggest that FSC are involved in the pituitary pars distalis paracrine regulation of the viscacha. PMID- 20353905 TI - Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3. AB - Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer .The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively. Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15 3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together, could be adopted as a panel of prognostic factors in the evaluation of the gallbladder carcinoma. PMID- 20353909 TI - Shared Y chromosome repetitive DNA sequences in stallion and donkey as visualized using whole-genomic comparative hybridization. AB - The genome of stallion (Spanish breed) and donkey (Spanish endemic Zamorano Leones) were compared using whole comparative genomic in situ hybridization (W CGH) technique, with special reference to the variability observed in the Y chromosome. Results show that these diverging genomes still share some highly repetitive DNA families localized in pericentromeric regions and, in the particular case of the Y chromosome, a sub-family of highly repeated DNA sequences, greatly expanded in the donkey genome, accounts for a large part of the chromatin in the stallion Y chromosome. PMID- 20353910 TI - Thymosin beta 4 expression in normal skin, colon mucosa and in tumor infiltrating mast cells. AB - Mast cells (MCs) are metachromatic cells that originate from multipotential hemopoietic stem cells in the bone marrow. Two distinct populations of MCs have been characterized: mucosal MCs are tryptase-positive while mast cells in skin contain tryptase and chymase. We now show that a sub-population of MCs is highly immunoreactive for thymosin beta4, as revealed by immunohistochemical analyses of normal skin, normal colon mucosa and salivary gland tumors. Four consecutive serial sections from each case were immunostained for thymosin beta4 (Tbeta4), chymase, tryptase and stained for toluidine blue. In skin biopsies, MCs showed a comparable immunoreactivity for Tbeta4, chymase and tryptase. In normal colon mucosa the vast majority of mucosal MCs expressed a strong cytoplasmic immunoreactivity for tryptase and for Tbeta4, in the absence of chymase reactivity. A robust expression of Tbeta4 was detected in tumor-infiltrating and peritumoral mast cells in salivary gland tumors and breast ductal infiltrating carcinomas. Tumor-infiltrating MCs also showed a strong immunoreactivity for chymase and tryptase. In this paper, we first demonstrate that normal dermal and mucosal mast cells exhibit strong expression of thymosin beta4, which could be considered a new marker for the identification of mast cells in skin biopsies as well as in human tumors. The possible relationship between the degree of Tbeta4 expression in tumor-infiltrating mast cells and tumor behaviour warrants further consideration in future investigations. PMID- 20353911 TI - Histomorphometric evaluation of intestinal cellular immune responses in pigs immunized with live oral F4ac+ non-enterotoxigenic E. coli vaccine against postweaning colibacillosis. AB - Enterotoxigenic Escherichia coli (ETEC) infection is the most common type of porcine postweaning colibacillosis (PWC). Among fimbriae of porcine ETEC strains the best studied family of fimbriae are the members of F4 adhesins, existing in at least three variants: ab, ac, ad. Active immunization against porcine PWC is difficult due to: i) ETEC strains are only one of the essential predisposing factors, ii) the success of vaccinal antigen uptake depends on the presence of enterocyte receptors for F4 adhesins, iii) the intestinal immune system may react with tolerance or hypersensitivity to the same antigens depending on the dose and form of the vaccinal immunogen, and iv) kinetics of the specific immune responses may be different in the case of F4 (earlier) and the other ETEC adhesins, particularly F18 (later). The aim of this study was to test the effectiveness of a live attenuated F4ac+ non-ETEC vaccine against porcine PWC by analyzing quantitative differences in the small intestinal lymphoid and myeloid cell subsets of immunized (with or without levamisole given as an adjuvant) vs control non-immunized pigs. Four week-old pigs were intragastrically immunized with a vaccine candidate F4ac+ non-ETEC strain 2407 at day 0, challenged 7 days later with a virulent F4ac+ strain ETEC 11-800/1/94, euthanatized at day 13 and sampled for immunohistology. Non-immunized pigs received saline at day 0 and were processed as the principals. Immuno-phenotypes of lymphoid and myeloid cell subsets were demonstrated within jejunal and ileal mucosa by immunohistochemical avidin-biotin complex method and corresponding morphometric data were analyzed using software program Lucia G for digital image analyses. Monoclonal antibodies reactive with surface molecules on porcine immune cells such as CD3, CD45RA, CD45RC, CD21 and SWC3 enabled clear insight into distribution patterns and amount of these cells within the gut-associated lymphoid tissues (GALT) examined. The numbers of jejunal and ileal cell subsets tested were significantly increased (at P<0.5 or lower) in both principal groups (vaccinated or levamisole primed vaccinated) of pigs, compared to those recorded in the control non-vaccinated pigs. Based on the histomorphometric quantification of porcine intestinal immune cells from the GALT compartments tested, it is possible to differentiate the responses of pigs immunized by an experimental mucosal vaccine from those of non immunized pigs. PMID- 20353912 TI - Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve. AB - The mitral valve, as an active flap, forms the major part of the left ventricular inflow tract and therefore plays an important function in many aspects of left ventricular performance. The anterior leaflet of this valve is the largest and most ventrally placed of two leaflets that come together during ventricular systole to close the left atrioventricular orifice. Various neurotransmitters are responsible for different functions including controlling valve movement, inhibiting or causing the failure of impulse conduction in the valve and the sensation of pain. Nitric oxide acts as a gaseous free radical neurotransmitter, neuromediator and effective cardiovascular modulator. Acetyl-choline is known to function as a typical neurotransmitter. Histochemical methods for detection of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), as an indirect nitric oxide-synthase marker, and method for detection of acetylcholinesterase (AChE) were used. Both methods were performed on the same valve sample. A widespread distribution of nerve fibres was observed in the anterior leaflet of the mitral valve. The fine NADPH-d positive (nitrergic) nerve fibres were identified in all zones of valve leaflet. AChE positive (cholinergic) nerve fibres were identified forming dense network and fibres organized in stripes. Endocardial cells and vessels manifested heavy NADPH-d activity. Our observations suggest a different arrangement of nitrergic and cholinergic nerve fibres in the anterior leaflet of the mitral valve. The presence of nitrergic and cholinergic activity confirms the involvement of both neurotransmitters in nerve plexuses and other structures of mitral valve. PMID- 20353913 TI - Clathrin-dependent endocytosis of membrane-bound RANKL in differentiated osteoclasts. AB - Bone is continuously repaired and remodelled through well-coordinated activity of osteoblasts that form new bone and osteoclasts, which resorb it. Osteoblasts synthesize and secrete two key molecules that are important for osteoclast differentiation, namely the ligand for the receptor of activator of nuclear factor kappaB (RANKL) and its decoy receptor osteoprotegerin (OPG). Active membrane transport is a typical feature of the resorbing osteoclast during bone resorption. Normally, one resorption cycle takes several hours as observed by monitoring actin ring formation and consequent disappearance in vitro. During these cyclic changes, the cytoskeleton undergoes remarkable dynamic rearrangement. Active cells show a continuous process of exocytosis that plays an essential role in transport of membrane components, soluble molecules and receptor-mediated ligands thus allowing them to communicate with the environment. The processes that govern intracellular transport and trafficking in mature osteoclasts are poorly known. The principal methodological problem that have made these studies difficult is a physiological culture of osteoclasts that permit observing the vesicle apparatus in conditions similar to the in vivo conditions. In the present study we have used a number of morphological approaches to characterize the composition, formation and the endocytic and biosynthetic pathways that play roles in dynamics of differentiation of mature bone resorbing cells using a tri-dimensional system of physiologic coculture. PMID- 20353914 TI - Differential expression of KCNQ1 K+ channel in tubular cells of frog kidney. AB - The aim of this study was to evaluate KCNQ1 K+ channel expression in the frog kidney of Rana esculenta. KCNQ1 K+ channel, also known as KvLQT1, is the pore forming a-subunit of the IKs K+ channel, a delayed rectifier voltage-gated K+ channel, which has an important role in water and salt transport in the kidney and gastrointestinal tract. The expression of KCNQ1 K+ channel along tubular epithelium differs from species to species. In the present study the expression of KCNQ1 K+ channel in the frog kidney has been demonstrated by immunohistochemistry. The presence of KCNQ1 K+ channel was demonstrated in the epithelial cells of distal convoluted tubule and collecting duct. However, the pattern of expression of KCNQ1 K+ channel differs between distal convoluted tubules and collecting duct. All epithelial cells of distal convoluted tubules revealed basolateral expression of KCNQ1 K+ channel. On the contrary, only the single cells of collecting duct, probably intercalated cells, showed diffuse cell surface staining with antibodies against KCNQ1 K+ channel. These findings suggest that KCNQ1 K+ channel has cell-specific roles in renal potassium ion transport. PMID- 20353915 TI - Transfer of Fas (CD95) protein from the cell surface to the surface of polystyrene beads coated with anti-Fas antibody clone CH-11. AB - Mouse monoclonal anti-Fas (CD95) antibody clone CH-11 has been widely used in research on apoptosis. CH-11 has the ability to bind to Fas protein on cell surface and induce apoptosis. Here, we used polystyrene beads coated with CH-11 to investigate the role of lipid rafts in Fas-mediated apoptosis in SKW6.4 cells. Unexpectedly, by treatment of the cells with CH-11-coated beads Fas protein was detached from cell surface and transferred to the surface of CH-11-coated beads. Western blot analysis showed that Fas protein containing both extracellular and intracellular domains was attached to the beads. Fas protein was not transferred from the cells to the surface of the beads coated with other anti-Fas antibodies or Fas ligand. Similar phenomenon was observed in Jurkat T cells. Furthermore, CH 11-induced apoptosis was suppressed by pretreatment with CH-11-coated beads in Jurkat cells. These results suggest that CH-11 might possess distinct properties on Fas protein compared with other anti-Fas antibodies or Fas ligand, and also suggest that caution should be needed to use polystyrene beads coated with antibodies such as CH-11. PMID- 20353916 TI - First cytochemical study of haemocytes from the crab Carcinus aestuarii (Crustacea, Decapoda). AB - For the first time, a morphological study of haemocytes from the crab Carcinus aestuarii was carried out by means of light microscopy and differing cytochemical assays. Analysis of haemocyte size frequency distribution (performed by means of a Coulter Counter) revealed the presence of two distinct haemocyte fractions in C. aestuarii haemolymph, depending on cell size. The first fraction was of about 3-5 microm in diameter and 30-50 fL in volume, the second was of about 6-12 microm in diameter and over 200 fL in volume. Mean cell diameter and volume were 8.20+/-1.7 microm and 272.30+/-143.5 fL, respectively. Haemocytes observed under light microscope were distinguished in three cell types: granulocytes (28%; 11.94+/-1.43 microm in diameter) with evident cytoplasmic granules, semigranulocytes (27%; 12.38+/-1.76 microm in diameter) with less granules than granulocytes, and hyalinocytes (44%; 7.88+/-1.6 microm in diameter) without granules. In addition, a peculiar cell type was occasionally found (about 1%): it was 25-30 microm in diameter and had a great vacuole and a peripheral cytoplasm with granules. Granulocyte and semigranulocyte granules stained in vivo with Neutral Red, indicating that they were lysosomes. Giemsa's dye confirmed that granulocytes and semigranulocytes were larger than hyalinocytes. Pappenheim's panoptical staining and Ehrlich's triacid mixture allowed to distinguish granule containing cells (including semigranulocytes) in acidophils (64%), basophils (35%) and neutrophils (1%). Hyalinocytes showed always a basophilic cytoplasm. Haemocytes were positive to the PAS reaction for carbohydrates, even if cytoplasm carbohydrate distribution varied among cell types. Lastly, lipids were found on cell membrane and in cytoplasm of all haemocyte types in the form of black spots produced after Sudan Black B staining. The morphological characterisation of C. aestuarii haemocytes by light microscopy was necessary before performing both ultrastructural and functional studies of circulating cells. PMID- 20353917 TI - [Human herpesvirus 7]. AB - Human herpesvirus 7 known since 1990 is closely related to herpesvirus 6B. It replicates in human cells only after binding CD4 receptor. It establishes lifelong latency in infected cells, and its frequent reactivations result in asymptomatic virus shedding through saliva. Most children acquire infection by age 3 and 4, but in any later age group seronegative individuals are at risk of infection. Rarely, exanthema subitum or convulsions with fever in children, pityriasis rosea in young adults, lethal complications in immunocompromised persons with concomitant herpesvirus 6B and cytomegalovirus reactivation occur. The most important pathogenic changes are due to the altered cytokine and growth factor secretion from infected lymphocytes with subsequent chain reaction on immune and other cells. Antiviral antibodies are detected by commercial kits (immunofluorescence, ELISA, immunoblot), nucleic acid by nested polymerase chain reaction. The majority of conditions due to infection do not require antiviral medication, but the severe complications are treated with ganciclovir and its derivates or foscarnet and cidofovir. PMID- 20353918 TI - [Sport habits and sedentary lifestyle among elementary school children in Obuda, Hungary]. AB - Childhood obesity has become a worldwide epidemic. Declining physical activity is one of the major contributors. AIM: To obtain data on Hungarian primary school students' weight status, sport club participation and sedentary behaviors. METHODS: A cross-sectional survey was distributed to all primary schools (n=18) in Obuda, Budapest. Children (1648 boys, 1654 girls; 11.3+/-2.3 years) completed questionnaires about sedentary behaviors and sport participation. Height, weight and waist circumference were measured. RESULTS: According to the IOTF criteria, 14.5% of the children were overweight and 4.6% were obese. The rate of those children who did not attend any extracurricular sport increased parallel with age in both gender. At the lower end of the range, 15.3% of the 9-year-old boys and 21% of the 10-year old girls did not sport. These numbers increased up to 31.0% in boys and 53.8% in girls by the age of 15 years. Screening time on weekdays and on weekends was 2.2+/-1.9 and 3.6+/-2.6 hours/day, respectively. One third of participants (32.2%) spent >2 h/day in front of a screen on weekdays, whereas 61.8% did on weekends. CONCLUSIONS: The frequency of sedentary behaviors was high among urban Hungarian school children. Health promotion strategies should start in early ages. PMID- 20353919 TI - [Noncompacted cardiomyopathy in infants and children. Clinical findings and diagnostic techniques]. AB - Noncompaction of the ventricular myocardium (NcCM) represents an arrest in the normal process of myocardial compaction, and has only recently been recognized as a distinct form of cardiomyopathy. It was previously termed as "spongy myocardium" and it is an extremely rare form of CM especially in infants and children. The last 20 years 23 cases aged 3 days-17 years mean: 60,3 months were diagnosed with NcCM (previously "spongy CM") based on echo-morphological criteria in our Institute. Our purpose was to assess the diagnostic value of Echo/ and MRI using conventional Echo and TDI parameters. FOLLOW-UP: 0.5-17 years, mean 6.3 years. We introduced in our country the MRI, also in the pediatric population with NcCM. RESULT: Echo/MRI diagnosis was in good agreement in the diagnosis of pediatric NcCM. TEI index correlated well with MRI EF (r: 0.96, p<0.01). The prognosis of NcCM in infants was very poor, with a 43% half year mortality, with one successful heart transplantation. All children were stable hemodynamic condition for a longer period. We think our result will contribute to the early diagnosis, adequate treatment of NcCM with improvement of the prognosis, and to the better knowledge of prevalence and family screening of this very severe disease. PMID- 20353920 TI - [Nijmegen Breakage syndrome]. AB - Nijmegen Breakage syndrome is a rare, autosomal recessive disorder characterized by severe, combined immunodeficiency, recurrent sinopulmonary infections, chromosomal instability, radiosensitivity, predisposition to malignancy, a "bird like" facial appearance, progressive microcephaly, short stature, and mental retardation. The syndrome is caused by mutations in the NBS1 gene, which encodes a DNA-repair protein, named nibrin. The authors summarize current knowledge on molecular genetics, diagnostic characteristics and therapeutic options of this inborn error of innate immunity. PMID- 20353921 TI - [Dr. Gyorgy Szabo (1905-1982), PhD in medical science, senior specialist in ophthalmology]. PMID- 20353923 TI - Community health education in developing and developed nations; interventions and social networks. PMID- 20353925 TI - Intimate partner violence screening in the emergency department: U.S. medical residents' perspectives. AB - Intimate Partner Violence (IPV) is physical, psychological, or sexual harm committed by a current or former partner, spouse, boy/girlfriend. In the United States, the National Center for Injury Prevention and Control (2003) estimates that 1.5 million women experience physical assault each year while the lifetime prevalence rate of IPV for women reaches almost 30%. Given the frequency and range of injuries and other health-related problems that result from IPV, the medical system shows promise as a central source of service provision for large numbers of abused women and their children. However, identification rates of IPV in many medical settings are low. This article describes a study that examined focus group data from 25 physicians in residency training at an urban hospital in the United States. Physicians discussed their knowledge and attitudes about IPV screening in the emergency department (ED) setting and suggestions to address perceived barriers to such screening. These data depict multiple barriers to physician screening of IPV in the ED. Findings substantiate previous research and provide new direction for enhancing IPV identification, referral, and treatment mechanisms in the ED setting including alternatives to physician mandated universal screening. PMID- 20353924 TI - Fostering traditional health systems and ethnomedicine practices through a holistic approach: a pioneering community strategy from Southern India. AB - The ever-presence of traditional medicine and of medical practitioners in remote areas of the world is well documented by anthropological studies. However, the social, cultural, and environmental factors influencing health and traditional health systems have been analyzed separately, ignoring the interlinkages existing between them and the resulting synergies as well as the impact these will have on the multiple aspects of local communities. This case study attempts to overcome this shortcoming, by investigating the interrelationships between biodiversity conservation and the practice of ethnomedicine in Southern India as a basis to implement primary health care, enhance local livelihoods, and contribute to poverty alleviation through community-based entrepreneurial activities. PMID- 20353926 TI - Gender, personal networks, and drug use among rural African Americans. AB - One of the main unifying concepts of research examining gender variations in drug use behavior is the social network. Yet, research specifically focusing on how the social networks of these groups differ by gender is limited. Few studies have investigated the social networks of rural African Americans who use drugs. In this study, we compared the personal networks of 20 rural African-American men and women addicted to cocaine using social network analysis (SNA) methods. The data do not support strong assertions about gender differences in the personal networks of the study sample. However, the results of the study suggest that men tend to have more drug users in their networks than women, as well as less structurally cohesive networks. Women tend to include more men in their personal networks than men included women. Implications of the research results for network-based drug prevention intervention as well as the value of SNA methods for drug use research are discussed. PMID- 20353927 TI - Enhancing social support, hardiness, and acculturation to improve mental health among Asian Indian international students. AB - International students, upon relocation to a foreign country, undergo a major life event which can cause distress that can potentially affect their mental health. This study pilot tested an internet-based intervention to enhance the social support, hardiness, and acculturation among students of Asian Indian origin at a large midwestern university. A pretest-posttest randomized design was employed. The pretest was administered to 60 students who were then randomly assigned to experimental and comparison groups. The experimental group was offered online instruction about social support, hardiness, and acculturation through Blackboard over 2 months. The comparison group received an equivalent protocol based on general wellness. Repeated measures ANOVA was done which showed significant improvement in mental health variable (F(1, 37) = 4.768, p < 0.05). Recommendations for replicating such interventions in other groups of international students are presented. PMID- 20353928 TI - Mother's knowledge of sickle-cell anaemia in Nigeria. AB - The study ascertains knowledge of mothers of sufferers of sickle-cell anaemia specifically regarding aetiology of the disorder and acceptable medical care. One hundred fifty-seven mothers of children suffering from sickle-cell anaemia (HbSS) attending a haematology clinic of a general hospital in Lagos were randomly sampled and asked about the aetiology and their understanding of the rules of care using a short open-ended questionnaire. The mean age of the mothers was 37.4 and a significant majority belong to the lower socio-economic strata. Thirty-four percent reported having been informed of the hereditary basis of anaemia but 48.4% received no explanation. Doctors, nurses, and lay literature were the main sources of information on the condition, as well as its medical care. The considerable gaps in appropriate knowledge on sickle-cell anaemia in Nigeria observed indicates that adequate and properly-presented information to parents or guardians of patients should be an essential part of a comprehensive care plan. PMID- 20353929 TI - Access to skilled care at home during pregnancy and childbirth: Dhaka Bangladesh. AB - In Bangladesh the majority of childbirth takes place at home by unskilled persons. The objective of this study was to strengthen maternity care services through provision of skilled midwives and to explore people's perception of skilled birth attendants. As part of a quasi-experimental community trial conducted among selected urban area of Dhaka city, a group of skilled midwives were posted in selected urban centers between January to December 2002 to provide obstetric care services and some social mobilization activity in the community. Analysis of skilled midwives self-reported case records and monitory reports of the researchers was done on selected themes. The perception of the skilled midwife was not clear to people. They thought traditional birth attendants who conducts delivery over years were skilled midwives. Preparedness for obstetric emergency and birth planning was non-existent in the families. The skilled midwives were well accepted in the community but discouraged by center authority for home birth, apprehending that it will reduce their client flow and earning. Non-cooperation by other health care providers was common. PMID- 20353932 TI - Does tumor size trump biology? PMID- 20353933 TI - Integrating bevacizumab into the treatment of patients with early-stage breast cancer: focus on cardiac safety. AB - Significant advances have been made in the treatment of patients with breast cancer in recent years. As increasing numbers of patients become long-term survivors, there must be a greater focus on treatment-induced chronic toxicities, such as left ventricular dysfunction, congestive heart failure (CHF), and/or secondary treatment malignancies. More recently, the HER2-targeted monoclonal antibody (MoAb) trastuzumab has been found to increase the risk for CHF, particularly when used in combination with an anthracycline or in anthracycline pretreated patients. In early-stage breast cancer, CHF has been reported in up to 4% of trastuzumab-treated, anthracycline-pretreated patients. Given this background, the clinical development of bevacizumab, a MoAb to vascular endothelial growth factor, is proceeding--with careful consideration given to cardiac safety--in this setting. Cardiac toxicity has been reported in association with bevacizumab-based therapy in patients with advanced or metastatic breast cancer, many of whom were previously exposed to anthracyclines. Although there is currently little evidence to suggest that bevacizumab increases the risk or worsens the severity of cardiac events in these patients, it is anticipated that ongoing, well-designed prospective trials will fully evaluate the cardiac safety of bevacizumab in patients with early-stage breast cancer. This review analyzes the cardiac safety profile of bevacizumab in breast cancer, with a focus on early-stage disease, and the ongoing clinical development of this important new drug. PMID- 20353934 TI - Oncologists' recommendations for adjuvant therapy in hormone receptor-positive breast cancer patients of varying age and health status. AB - BACKGROUND: Currently, evidence supports the use of adjuvant endocrine therapy with aromatase inhibitors in post-menopausal patients with hormone receptor (HR) positive breast cancer. The goal of the current study is to understand the effect of patient age and health status on oncologists' decision to recommend adjuvant treatment (endocrine therapy and chemotherapy) in older women with HR-positive breast cancer. PATIENTS AND METHODS: An online survey was conducted, with questions related to a hypothetical patient of varying age and health status with a T2 N2 HR-positive, HER2-negative breast cancer. Treatment options included chemotherapy and endocrine therapy, endocrine therapy alone, or no therapy. Respondents (n = 151) were further asked to specify use of either tamoxifen or aromatase inhibitors. A generalized linear mixed-effects model was used to determine the effect of age and health status on recommendations. RESULTS: As the hypothetical patient's age increased or health status deteriorated, oncologists (n = 151) were less likely to recommend a combination of chemotherapy and endocrine therapy (P < .0001 for both). In contrast, oncologists were more likely to recommend endocrine therapy alone with advanced age and deteriorating health status (P < .0001 for both). Oncologists were more likely to choose treatment with aromatase inhibitors as opposed to tamoxifen (P < .01), irrespective of age or health status. CONCLUSION: With increasing age and declining health status, oncologists were more likely to recommend endocrine therapy alone as opposed to chemotherapy with endocrine therapy. Oncologists were most likely to recommend aromatase inhibitors, irrespective of age or health status. PMID- 20353936 TI - The effect of optimal medical therapy on 1-year mortality after acute myocardial infarction. AB - OBJECTIVES: Five drug classes have been shown to improve the prognosis of acute myocardial infarction in clinical trials: aspirin, beta-blockers, statins, renin angiotensin system (RAS) blockers and thienopyridines. We aimed to assess whether the benefits of combining these drugs (termed optimal medical therapy, OMT), will result in a reduction of mortality in clinical practice. DESIGN: Nationwide registry SETTING: Hospitals with a cardiology unit or internal medicine department. PATIENTS: 5353 patients with acute myocardial infarction. At hospital discharge 89% received aspirin, 90% beta-blockers, 84% statins, 81% RAS blockers, 70% a thienopyridine and 46.2% OMT. INTERVENTIONS: Pharmacotherapy MAIN OUTCOME MEASURES: OR with 95% CI for mortality from myocardial infarction were calculated and adjusted for patient risk at baseline. RESULTS: Total mortality was reduced by 74% in patients receiving OMT (adj OR 0.26; 95% CI 0.18 to 0.38) versus patients receiving one or no drug. This was consistent in subgroups defined by STEMI/NSTEMI, diabetes and gender. Mortality was also reduced in patients receiving 2-4 drugs (adj OR 0.49; 95% CI 0.35 to 0.68), diabetic patients being the only subgroup with no significant effect. Analyses on the relative importance of either component revealed that withdrawal of beta-blockers (adj OR 0.63; 95% CI 0.34 to 1.16) and/or a combination of aspirin/clopidogrel (adj OR 0.59; 95% CI 0.20 to 1.17) abolished the risk reduction conferred by OMT. CONCLUSIONS: OMT over 1 year was associated with a significantly lower mortality of patients with acute myocardial infarction in clinical practice. However OMT is provided to less than half of eligible patients leaving room for substantial improvement. PMID- 20353937 TI - Cis and trans actions of the cholinesterase-like domain within the thyroglobulin dimer. AB - Thyroglobulin (Tg, precursor for thyroid hormone synthesis) is a large secreted glycoprotein composed of upstream regions I-II-III, followed by the approximately 570 residue cholinesterase-like (ChEL) domain. ChEL has two identified functions: 1) homodimerization, and 2) binding to I-II-III that facilitates I-II-III oxidative maturation required for intracellular protein transport. Like its homologs in the acetylcholinesterase (AChE) family, ChEL possesses two carboxyl terminal alpha-helices. We find that a Tg-AChE chimera (swapping AChE in place of ChEL) allows for dimerization with monomeric AChE, proving exposure of the carboxyl-terminal helices within the larger context of Tg. Further, we establish that perturbing trans-helical interaction blocks homodimerization of the Tg ChEL domain. Additionally, ChEL can associate with neuroligins (a related family of cholinesterase-like proteins), demonstrating potential for Tg cross-dimerization between non-identical partners. Indeed, when mutant rdw-Tg (Tg-G2298R, defective for protein secretion) is co-expressed with wild-type Tg, the two proteins cross dimerize and secretion of rdw-Tg is partially restored. Moreover, we find that AChE and soluble neuroligins also can bind to the upstream Tg regions I-II-III; however, they cannot rescue secretion, because they cannot facilitate oxidative maturation of I-II-III. These data suggest that specific properties of distinct Tg ChEL mutants may result in distinct patterns of Tg monomer folding, cross dimerization with wild-type Tg, and variable secretion behavior in heterozygous patients. PMID- 20353938 TI - Identification of a novel cell death receptor mediating IGFBP-3-induced anti tumor effects in breast and prostate cancer. AB - Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP 3 have been reported to be independent of IGFs, but the precise biochemical/molecular mechanisms of IGF-independent, antiproliferative actions of IGFBP-3 are largely unknown. Here we report a new cell death receptor, IGFBP-3R, that is a single-span membrane protein and binds specifically to IGFBP-3 but not other IGFBP species. Expression analysis of IGFBP-3 and IGFBP-3R indicates that the IGFBP-3/IGFBP-3R axis is impaired in breast and prostate cancer. We also provide evidence for anti-tumor effect of IGFBP-3R in vivo using prostate and breast cancer xenografts in athymic nude mice. Further in vitro studies demonstrate that IGFBP-3R mediates IGFBP-3-induced caspase-8-dependent apoptosis in various cancer cells. Knockdown of IGFBP-3R attenuated IGFBP-3-induced caspase activities and apoptosis, whereas overexpression of IGFBP-3R enhanced IGFBP-3 biological effects. IGFBP-3R physically interacts and activates caspase-8, and knockdown of caspase-8 expression or activity inhibited IGFBP-3/IGFBP-3R-induced apoptosis. Here, we propose that IGFBP-3R represents a novel cell death receptor and is essential for the IGFBP-3-induced apoptosis and tumor suppression. Thus, the IGFBP-3/IGFBP-3R axis may provide therapeutic and prognostic value for the treatment of cancer. PMID- 20353939 TI - Activation of noncanonical NF-kappaB signaling by the oncoprotein Tio. AB - NF-kappaB transcription factors are key regulators of cellular proliferation and frequently contribute to oncogenesis. The herpesviral oncoprotein Tio, which promotes growth transformation of human T cells in a recombinant herpesvirus saimiri background, potently induces canonical NF-kappaB signaling through membrane recruitment of the ubiquitin ligase tumor necrosis factor receptor associated factor 6 (TRAF6). Here, we show that, in addition to Tio-TRAF6 interaction, the Tio-induced canonical NF-kappaB signal requires the presence of the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, NF-kappaB essential modulator (NEMO), and the activity of its key kinase, IKKbeta, to up regulate expression of endogenous cellular inhibitor of apoptosis 2 (cIAP2) and interleukin 8 (IL-8) proteins. Dependent on TRAF6 and NEMO, Tio enhances the expression of the noncanonical NF-kappaB proteins, p100 and RelB. Independent of TRAF6 and NEMO, Tio mediates stabilization of the noncanonical kinase, NF-kappaB inducing kinase (NIK). Concomitantly, Tio induces efficient processing of the p100 precursor molecule to its active form, p52, as well as DNA binding of nuclear p52 and RelB. In human T cells transformed by infection with a Tio recombinant virus, sustained expression of p100, RelB, and cIAP2 depends on IKKbeta activity, yet processing to p52 remains largely unaffected by IKKbeta inhibition. However, long term inhibition of IKKbeta disrupts the continuous growth of the transformed cells and induces cell death. Hence, the Tio oncoprotein triggers noncanonical NF-kappaB signaling through NEMO-dependent up regulation of p100 precursor and RelB, as well as through NEMO-independent generation of p52 effector. PMID- 20353940 TI - The human Cdc34 carboxyl terminus contains a non-covalent ubiquitin binding activity that contributes to SCF-dependent ubiquitination. AB - Cdc34 is an E2 ubiquitin-conjugating enzyme that functions in conjunction with SCF (Skp1.Cullin 1.F-box) E3 ubiquitin ligase to catalyze covalent attachment of polyubiquitin chains to a target protein. Here we identified direct interactions between the human Cdc34 C terminus and ubiquitin using NMR chemical shift perturbation assays. The ubiquitin binding activity was mapped to two separate Cdc34 C-terminal motifs (UBS1 and UBS2) that comprise residues 206-215 and 216 225, respectively. UBS1 and UBS2 bind to ubiquitin in the proximity of ubiquitin Lys(48) and C-terminal tail, both of which are key sites for conjugation. When bound to ubiquitin in one orientation, the Cdc34 UBS1 aromatic residues (Phe(206), Tyr(207), Tyr(210), and Tyr(211)) are probably positioned in the vicinity of ubiquitin C-terminal residue Val(70). Replacement of UBS1 aromatic residues by glycine or of ubiquitin Val(70) by alanine decreased UBS1-ubiquitin affinity interactions. UBS1 appeared to support the function of Cdc34 in vivo because human Cdc34(1-215) but not Cdc34(1-200) was able to complement the growth defect by yeast Cdc34 mutant strain. Finally, reconstituted IkappaBalpha ubiquitination analysis revealed a role for each adjacent pair of UBS1 aromatic residues (Phe(206)/Tyr(207), Tyr(210)/Tyr(211)) in conjugation, with Tyr(210) exhibiting the most pronounced catalytic function. Intriguingly, Cdc34 Tyr(210) was required for the transfer of the donor ubiquitin to a receptor lysine on either IkappaBalpha or a ubiquitin in a manner that depended on the neddylated RING sub-complex of the SCF. Taken together, our results identified a new ubiquitin binding activity within the human Cdc34 C terminus that contributes to SCF-dependent ubiquitination. PMID- 20353941 TI - CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin. AB - A hallmark feature of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) regulation is the generation of Ca(2+)-independent autonomous activity by Thr-286 autophosphorylation. CaMKII autonomy has been regarded a form of molecular memory and is indeed important in neuronal plasticity and learning/memory. Thr-286-phosphorylated CaMKII is thought to be essentially fully active ( approximately 70-100%), implicating that it is no longer regulated and that its dramatically increased Ca(2+)/CaM affinity is of minor functional importance. However, this study shows that autonomy greater than 15-25% was the exception, not the rule, and required a special mechanism (T-site binding; by the T-substrates AC2 or NR2B). Autonomous activity toward regular R-substrates (including tyrosine hydroxylase and GluR1) was significantly further stimulated by Ca(2+)/CaM, both in vitro and within cells. Altered K(m) and V(max) made autonomy also substrate- (and ATP) concentration-dependent, but only over a narrow range, with remarkable stability at physiological concentrations. Such regulation still allows molecular memory of previous Ca(2+) signals, but prevents complete uncoupling from subsequent cellular stimulation. PMID- 20353942 TI - Dysfunction of the Scn8a voltage-gated sodium channel alters sleep architecture, reduces diurnal corticosterone levels, and enhances spatial memory. AB - Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also proposed in studies examining the genetic basis of attempted suicide and bipolar disorder. In addition, mice with a Scn8a loss-of-function mutation (Scn8a(med-Tg/+)) show altered anxiety and depression-like phenotypes. Because psychiatric abnormalities are often associated with altered sleep and hormonal patterns, we evaluated heterozygous Scn8a(med-jo/+) mutants for alterations in sleep-wake architecture, diurnal corticosterone levels, and behavior. Compared with their wild-type littermates, Scn8a(med-jo/+) mutants experience more non-rapid eye movement (non-REM) sleep, a chronic impairment of REM sleep generation and quantity, and a lowered and flattened diurnal rhythm of corticosterone levels. No robust differences were observed between mutants and wild-type littermates in locomotor activity or in behavioral paradigms that evaluate anxiety or depression-like phenotypes; however, Scn8a(med-jo/+) mutants did show enhanced spatial memory. This study extends the spectrum of phenotypes associated with mutations in Scn8a and suggests a novel role for altered sodium channel function in human sleep disorders. PMID- 20353943 TI - Stabilization of G domain conformations in the tRNA-modifying MnmE-GidA complex observed with double electron electron resonance spectroscopy. AB - MnmE is a GTP-binding protein conserved between bacteria and eukarya. It is a dimeric three-domain protein where the two G domains have to approach each other for activation of the potassium-stimulated GTPase reaction. Together with GidA, in a heterotetrameric alpha(2)beta(2) complex, it is involved in the modification of the wobble uridine base U34 of the first anticodon position of particular tRNAs. Here we show, using various spin-labeled MnmE mutants and EPR spectroscopy, that GidA binding induces large conformational and dynamic changes in MnmE. It stimulates the GTPase reaction by stabilizing the GTP-bound conformation in a potassium-independent manner. Surprisingly, GidA binding influences not only the GTP- but also the GDP-bound conformation. Thus GidA is a new type of regulator for a G protein activated by dimerization. PMID- 20353944 TI - Differential requirements of Hsp90 and DNA for the formation of estrogen receptor homodimers and heterodimers. AB - The two estrogen receptor (ER) subforms, ERalpha and ERbeta, are capable of forming DNA-binding homodimers and heterodimers. Although binding to DNA is thought to stabilize ER dimers, how ERalpha/alpha, ERbeta/beta, and ERalpha/beta dimerization is regulated by DNA and the chaperone protein Hsp90 is poorly understood. Using our highly optimized bioluminescence resonance energy transfer assays in conjunction with assays for transcriptional activation of ERs, we determined that DNA binding appears to play a minor role in the stabilization of ER dimers, especially in the case of ERbeta/beta homodimers. These findings suggest that ER dimers form before they associate with chromatin and that DNA binding plays a minor role in stabilizing ER dimers. Additionally, although Hsp90 is essential for the proper dimerization of ERalpha/alpha and ERalpha/beta, it is not required for the proper dimerization of ERbeta/beta. Despite this, Hsp90 is critical for the estrogen-dependent transcriptional activity of the ERbeta/beta homodimer. Thus, Hsp90 is implicated as an important regulator of distinct aspects of ERalpha and ERbeta action. PMID- 20353945 TI - Secretory mechanisms and intercellular transfer of microRNAs in living cells. AB - The existence of circulating microRNAs (miRNAs) in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function of extracellular miRNAs remain unclear. Here, we show that miRNAs are released through a ceramide dependent secretory machinery and that the secretory miRNAs are transferable and functional in the recipient cells. Ceramide, whose biosynthesis is regulated by neutral sphingomyelinase 2 (nSMase2), triggers secretion of small membrane vesicles called exosomes. The decreased activity of nSMase2 with a chemical inhibitor, GW4869, and a specific small interfering RNA resulted in the reduced secretion of miRNAs. Complementarily, overexpression of nSMase2 increased extracellular amounts of miRNAs. We also revealed that the endosomal sorting complex required for transport system is unnecessary for the release of miRNAs. Furthermore, a tumor-suppressive miRNA secreted via this pathway was transported between cells and exerted gene silencing in the recipient cells, thereby leading to cell growth inhibition. Our findings shed a ray of light on the physiological relevance of secretory miRNAs. PMID- 20353946 TI - Protein kinase RNA/FADD/caspase-8 pathway mediates the proapoptotic activity of the RNA-binding protein human antigen R (HuR). AB - The RNA-binding protein human antigen R (HuR) has been implicated in apoptosis in multiple ways. Several studies have shown that in response to a variety of stresses HuR promotes the expression of proapoptotic mRNAs, whereas others reported its regulatory effect on antiapoptotic messages. We recently showed that in response to severe stress, HuR is cleaved to generate two cleavage products (CPs), HuR-CP1 (24 kDa) and HuR-CP2 (8 kDa), by which it promotes apoptotic cell death. Here, we show that this cleavage event is dependent on protein kinase RNA (PKR). Surprisingly, although in response to the apoptotic inducer staurosporine PKR itself is not phosphorylated, PKR triggers the cleavage of HuR via its downstream effector FADD that in turn activates the caspase-8/caspase-3 pathway. This effect, however, does not require the phosphorylation of the eukaryotic translation initiation factor 2alpha. Additionally, we observed that these HuR CPs are sufficient to trigger cell death in the absence of activation of the PKR pathway. Therefore, our results support a model whereby in response to lethal stress, PKR, without being phosphorylated, activates the FADD/caspase-8/caspase-3 pathway to trigger HuR cleavage, and the HuR-CPs are then capable of promoting apoptosis. PMID- 20353947 TI - trans-10,cis-12-Conjugated linoleic acid instigates inflammation in human adipocytes compared with preadipocytes. AB - We showed previously in cultures of primary human adipocytes and preadipocytes that lipopolysaccharide and trans-10,cis-12-conjugated linoleic acid (10,12-CLA) activate the inflammatory signaling that promotes insulin resistance. Because our published data demonstrated that preadipocytes are the primary instigators of inflammatory signaling in lipopolysaccharide-treated cultures, we hypothesized that they played the same role in 10,12-CLA-mediated inflammation. To test this hypothesis, we employed four distinct models. In model 1, a differentiation model, CLA activation of MAPK and induction of interleukin-8 (IL-8), IL-6, IL 1beta, and cyclo-oxygenase-2 (COX-2) were greatest in differentiated compared with undifferentiated cultures. In model 2, a cell separation model, the mRNA levels of these inflammatory proteins were increased by 10,12-CLA compared with bovine serum albumin vehicle in the adipocyte fraction and the preadipocyte fraction. In model 3, a co-culture insert model, inserts containing approximately 50% adipocytes (AD50) or approximately 100% preadipocytes (AD0) were suspended over wells containing AD50 or AD0 cultures. 10,12-CLA-induced IL-8, IL-6, IL 1beta, and COX-2 mRNA levels were highest in AD50 cultures when co-cultured with AD0 inserts. In model 4, a conditioned medium (CM) model, CM collected from CLA treated AD50 but not AD0 cultures induced IL-8 and IL-6 mRNA levels and activated phosphorylation of MAPK in naive AD0 and AD50 cultures. Consistent with these data, 10,12-CLA-mediated secretions of IL-8 and IL-6 from AD50 cultures were higher than from AD0 cultures. Notably, blocking adipocytokine secretion prevented the inflammatory capacity of CM from 10,12-CLA-treated cultures. These data suggest that CLA instigates the release of inflammatory signals from adipocytes that subsequently activate adjacent preadipocytes. PMID- 20353948 TI - RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53. AB - Although it has been shown that the gastric tumor suppressor RUNX3 has a growth inhibitory activity, the precise molecular mechanisms behind RUNX3-mediated tumor suppression remained unclear. In this study, we found that RUNX3 is closely involved in DNA damage-dependent phosphorylation of tumor suppressor p53 at Ser 15 and acts as a co-activator for p53. The small interference RNA-mediated knockdown of RUNX3 inhibited adriamycin (ADR)-dependent apoptosis in p53 proficient cells but not in p53-deficient cells in association with a significant reduction of p53-target gene expression as well as phosphorylation of p53 at Ser 15. In response to ADR, RUNX3 was induced to accumulate in the cell nucleus and co-localized with p53. Immunoprecipitation experiments demonstrated that RUNX3 forms a complex with p53 in cells. In vitro pulldown assays revealed that the COOH-terminal portion of p53 is required for the interaction with RUNX3. Forced expression of RUNX3 enhanced p53-mediated transcriptional activation. Additionally, RUNX3 had an ability to induce the phosphorylation of p53 at Ser 15, thereby promoting p53-dependent apoptosis. Intriguingly, RUNX3 interacted with phosphorylated forms of ataxia telangiectasia-mutated in response to ADR; however, it did not affect the extent of DNA damage. From the clinical point of view, coordinated p53 mutation and decreased expression of RUNX3 in 105 human lung adenocarcinomas were significantly associated with the poor outcome of patients (p = 0.0203). Thus, our present results strongly suggest that RUNX3 acts as a novel co-activator for p53 through regulating its DNA damage-induced phosphorylation at Ser-15 and also provide a clue to understanding the molecular mechanisms underlying RUNX3-mediated tumor suppression. PMID- 20353949 TI - The catecholaminergic polymorphic ventricular tachycardia mutation R33Q disrupts the N-terminal structural motif that regulates reversible calsequestrin polymerization. AB - Calsequestrin undergoes dynamic polymerization with increasing calcium concentration by front-to-front dimerization and back-to-back packing, forming wire-shaped structures. A recent finding that point mutation R33Q leads to lethal catecholaminergic polymorphic ventricular tachycardia (CPVT) implies a crucial role for the N terminus. In this study, we demonstrate that this mutation resides in a highly conserved alternately charged residue cluster (DGKDR; cluster 1) in the N-terminal end of calsequestrin. We further show that this cluster configures itself as a ring system and that the dipolar arrangement within the cluster brings about a critical conformational flip of Lys(31)-Asp(32) essential for dimer stabilization by formation of a H-bond network. We additionally show that Ca(2+)-induced calsequestrin aggregation is nonlinear and reversible and can regain the native conformation by Ca(2+) chelation with EGTA. This study suggests that cluster 1 works as a molecular switch and governs the bidirectional transition between the CASQ2 monomer and dimer. We further demonstrate that mutations disrupting the alternating charge pattern of the cluster, including R33Q, impair Ca(2+)-CASQ2 interaction, leading to altered polymerization depolymerization dynamics. This study provides new mechanistic insight into the functional effects of the R33Q mutation and its potential role in CPVT. PMID- 20353953 TI - The effects of gender and a co-occurring depressive disorder on neurocognitive functioning in patients with alcohol dependence. AB - AIMS: The present study aims to examine neuropsychological impairments by comorbidity and gender among patients with alcohol dependence. METHODS: The study sample is comprised of 123 subjects who fulfilled a Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) diagnosis of alcohol dependence from January 2006 to December 2007. Subjects were asked to complete the following psychological tests: the Barratt Impulsivity Scale (BIS), Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Color Trails Test. We compared the results of neuropsychological assessments based on two types of classifications: people with comorbid depression and people without comorbidity; females and males. RESULTS: The immediate visual memory and the BIS scores in patients with comorbid depression were significantly different from the scores in patients without comorbidity. In addition, females performed significantly poorer on the Working Memory Index than males and had a later age of regular drinking. CONCLUSIONS: Further investigation of the mechanism associated with the gender difference on cognition and exploration of the temporal relationship between alcohol dependence and depressive disorder on the cognitive aspect is needed. PMID- 20353950 TI - AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15S-hydroxyeicosatetraenoic acid-induced angiogenesis. AB - To understand the involvement of matrix metalloproteinases (MMPs) in 15(S) hydroxyeicosatetraenoic acid (15(S)-HETE)-induced angiogenesis, we have studied the role of MMP-2. 15(S)-HETE induced MMP-2 expression and activity in a time dependent manner in human dermal microvascular endothelial cells (HDMVECs). Inhibition of MMP-2 activity or depletion of its levels attenuated 15(S)-HETE induced HDMVEC migration, tube formation, and Matrigel plug angiogenesis. 15(S) HETE also induced Fra-1 and c-Jun expression in a Rac1-MEK1-JNK1-dependent manner. In addition, 15(S)-HETE-induced MMP-2 expression and activity were mediated by Rac1-MEK1-JNK1-dependent activation of AP-1 (Fra-1/c-Jun). Cloning and site-directed mutagenesis of MMP-2 promoter revealed that AP-1 site proximal to the transcriptional start site is required for 15(S)-HETE-induced MMP-2 expression, and Fra-1 and c-Jun are the essential components of AP-1 that bind to MMP-2 promoter in response to 15(S)-HETE. Hind limb ischemia led to an increase in MEK1 and JNK1 activation and Fra-1, c-Jun, and MMP-2 expression resulting in enhanced neovascularization and recovery of blood perfusion in wild-type mice as compared with 12/15-Lox(-/-) mice. Together, these results provide the first direct evidence for a role of 12/15-Lox-12/15(S)-HETE axis in the regulation of ischemia-induced angiogenesis. PMID- 20353954 TI - Esmond E. Snell--the pathfinder of B vitamins and cofactors. AB - Esmond E. Snell (1914-2003) was a giant of B-vitamin and enzyme research. His early research in bacterial nutrition had lead to the discovery of vitamins such as lipoic acid and folic acid, and an anti-vitamin avidin. He developed microbiological assay methods for riboflavin and other vitamins and amino acids, which are still used today. He also investigated the metabolism of vitamins, discovered pyridoxal and pyridoxamine as the active forms of vitamin B(6) and revealed the mechanism of transamination and other reactions catalysed by vitamin B(6) enzymes. His research in later years on pyruvoyl-dependent histidine decarboxylase unveiled the biogenesis mechanism of this first built-in cofactor. Throughout his career, he was a great mentor of many people, all of whom are inspired by his philosophy of science. PMID- 20353955 TI - Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. AB - Leopard Complex spotting occurs in several breeds of horses and is caused by an incompletely dominant allele (LP). Homozygosity for LP is also associated with congenital stationary night blindness (CSNB) in Appaloosa horses. Previously, LP was mapped to a 6 cm region on ECA1 containing the candidate gene TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) and decreased expression of this gene, measured by qRT-PCR, was identified as the likely cause of both spotting and ocular phenotypes. This study describes investigations for a mutation causing or associated with the Leopard Complex and CSNB phenotype in horses. Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs. Most of the SNPs did not have a predictive value for the presence of LP. However, one SNP (ECA1:108,249,293 C>T) found within intron 11 had a strong (P < 0.0005), but not complete, association with LP and CSNB and thus is a good marker but unlikely to be causative. To further localize the association, 70 SNPs spanning over two Mb including the TRPM1 gene were genotyped in 192 horses from three different breeds segregating for LP. A single 173 kb haplotype associated with LP and CSNB (ECA1: 108,197,355- 108,370,150) was identified. Illumina sequencing of 300 kb surrounding this haplotype revealed 57 SNP variants. Based on their localization within expressed sequences or regions of high sequence conservation across mammals, six of these SNPs were considered to be the most likely candidate mutations. While the precise function of TRPM1 remains to be elucidated, this work solidifies its functional role in both pigmentation and night vision. Further, this work has identified several potential regulatory elements of the TRPM1 gene that should be investigated further in this and other species. PMID- 20353956 TI - Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis. AB - OBJECTIVES: Fatigue is a frequently experienced and patient-relevant complaint in RA. Disease activity, anaemia and pain are regarded as disease-related factors that may lead to fatigue in RA. However, psychosocial factors may also play a role in maintaining severe fatigue. The objectives of this study were to determine the prevalence of severe fatigue in RA patients, to study patient perceptions of fatigue and to determine which disease-related factors and psychosocial factors are independently associated with fatigue severity. METHODS: For this study consecutive RA outpatients were enrolled (n = 228). The patients filled out questionnaires regarding fatigue using the Checklist Individual Strength (CIS), including psychosocial factors, pain and disability. The clinical data that were collected included ESR, CRP, haemoglobin level and 28-joint disease activity score (DAS-28). Chunk-wise backward linear regression was used for analysis. RESULTS: Severe fatigue (CIS > or = 35) was experienced by 42% of the RA patients, and they perceived their fatigue as frustrating or exhausting. The severely fatigued RA patients scored worse on all measured psychosocial items, compared with patients without severe fatigue. Pain severity, role functioning, depressive mood, self-efficacy on fatigue, worrying, helplessness and non-restorative sleep were the factors most strongly associated with fatigue level. CONCLUSIONS: A considerable proportion of RA patients had severe fatigue, with fatigue levels similar to chronic fatigue syndrome. Fatigue in RA was related to pain and functioning, not inflammation, as disease-related factors and to several psychosocial factors including coping and cognitions concerning fatigue. PMID- 20353957 TI - Acute peritoneal dialysis: what is the 'adequate' dose for acute kidney injury? PMID- 20353959 TI - Association between social adaptability index and survival of patients with chronic kidney disease. AB - BACKGROUND: While individual socioeconomic factors have been associated with clinical outcome, a composite index has not been developed. In this project, we tested the hypothesis that Social Adaptability Index (SAI) based on employment, education, income, marital status and substance abuse is associated with survival in chronic kidney disease (CKD) patients. METHODS: This is a retrospective cohort study of patients with CKD stage 2 or greater. We used the Third National Health and Nutrition Examination Survey (NHANES III) cohort data between 1988 and 1994 including those 18 years or older. Our primary variable of interest is SAI. Each component of SAI (employment status, education, marital status, and substance abuse) has been graded on the scale of 0-3, income has been graded on the scale 0 1. Age, sex, race, diabetes, co-morbidity index, body mass index (BMI), geographic location, haemoglobin, serum creatinine, serum albumin, serum cholesterol and Hba1c were used as covariates in multivariate analysis. The outcome of the study is patient's mortality. The time to death was calculated as time between the first interview by NHANES and death. RESULTS: We analysed 13 400 subjects with mean age of 50.6 +/- 20-53.6% males, 44.4% white, 29.7% African American and 22.1% Mexican American-with 8.5% having diabetes, with an average number of co-morbid conditions of 2.7 +/- 1.1. Lower SAI is associated with greater stage of CKD. Higher SAI was associated with decreased mortality [hazard ratio (HR) 0.88, P < 0.001, 95% confidence interval (CI) 0.86-0.89]. When SAI quintiles were analysed, we demonstrated a 'dose-dependent' association between SAI and survival. Subgroup analysis showed that this association of SAI and survival was present in all studied subgroups. The limitations of the study include retrospective design, potential misreporting and misclassification, and reverse causality. CONCLUSION: We demonstrated that SAI has a strong and clinically significant association with mortality in CKD patients. PMID- 20353958 TI - Chronic kidney disease and venous thromboembolism: a prospective study. AB - BACKGROUND: The incidence of venous thromboembolism (VTE) is increased with severe kidney disease, but whether less-severe chronic kidney disease (CKD) increases the risk of VTE is less certain. METHODS: We studied this in a prospective cohort of 10 700 whites and African Americans, aged 53-75 years, attending Visit 4 (1996-98) of the Atherosclerosis Risk in Communities Study. Estimated glomerular filtration rate (eGFR) values were estimated from prediction equations based on serum creatinine (eGFR(creat)) or cystatin C (eGFR(cys)). Normal kidney function was defined as eGFR >=90 ml/min/1.73 m(2), mildly decreased kidney function as eGFR between 60 and 89 ml/min/1.73 m(2) and Stage 3 to 4 CKD as eGFR between 15 and 59 ml/min/1.73 m(2). VTE occurrence (n = 228) was ascertained over a median of 8.3 years. RESULTS: For eGFR(cys), the age-, race- and sex-adjusted hazard ratios of total VTE were 1.0, 1.40 and 1.94 (P trend = 0.003) for normal kidney function, mildly impaired kidney function and Stage 3 to 4 CKD, respectively. These respective hazard ratios were moderately attenuated to 1.0, 1.26 and 1.60 (P trend = 0.04) with adjustment for hormone replacement therapy, diabetes and body mass index. Associations between CKD based on eGFR(cys) and VTE were slightly stronger for idiopathic VTE than for secondary VTE. In contrast, CKD based on eGFR(creat) was not associated with total VTE occurrence. CONCLUSIONS: Stage 3 to 4 CKD, based on eGFR(cys) but not eGFR(creat), was associated with an approximately 1.6-fold increased risk of VTE. PMID- 20353960 TI - Small solutes peritoneal membrane transport and endothelial function. PMID- 20353961 TI - Targeted metabolic reconstruction: a novel approach for the characterization of plant-pathogen interactions. AB - Genome-scale metabolic reconstruction (GEMR), along with flux balance analysis, has been widely used to study complex metabolic networks in several microbial organisms. This approach is of particular applicability in biological systems where the lack of kinetics data is typical. This is the case of plant-pathogen interactions, where these methods open the possibility of studying host metabolic network phenotype during the interaction with pathogens. Since GEMRs are based on sequenced genomes, its applicability to organisms where genomic information is lacking is limited. Here we describe an alternative approach to GEMR: targeted metabolic reconstruction, where network reconstruction is guided by transcriptomic data instead of genomic information. This approach is being applied successfully in our laboratory for the Phytophthora infestans--Solanum tuberosum pathosystem. PMID- 20353962 TI - Atrial autonomic innervation remodelling and atrial fibrillation inducibility after epicardial ganglionic plexi ablation. AB - AIMS: The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated. METHODS AND RESULTS: Thirteen dogs were randomly divided into sham operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/ 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively). CONCLUSION: Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation. PMID- 20353963 TI - Magnetic resonance imaging of pacemakers and implantable cardioverter defibrillators without specific absorption rate restrictions. AB - AIMS: The purpose of the current study is to evaluate the safety profile of patients with pacemakers or implantable cardioverter-defibrillators (ICDs) undergoing a medically necessary magnetic resonance imaging (MRI) scan without limitation on peak specific absorption rate (SAR). Recent series suggest that MRI scanning can be performed safely in select patients with pacemakers or ICDs. These studies, though, limited peak SAR. METHODS AND RESULTS: One-hundred and three patients with a total of 240 leads underwent a total of 127 scans of any body landmark using usual protocols with standard peak SAR settings for the scan. No patient was pacemaker dependent. Thresholds were obtained immediately before and after the scan. For all scans, the median (25th and 75th percentiles) peak SAR was 2.5 (1.3, 3.2) W/kg whereas the median scan time was 1650 (1236, 2099) s. Pre- and post-scan pacing thresholds were unchanged [0.7 (0.5, 0.8) vs. 0.6 (0.5, 0.8) V at 0.5 ms, P=NS], though the sensed amplitudes [6.7 (2.9, 11.5) vs. 6.1 (2.9, 11.2) mV, P<0.0001] and pacing impedances [500 (440, 609) vs. 491 (437, 593) Omega, P<0.0001] both decreased significantly. CONCLUSION: The current series suggests that MRI scans may be performed safely in appropriately selected patients up to a peak SAR of 3.2 W/kg. Furthermore, peak SAR level poorly predicts the safety profile of patients with pacemakers or ICDS who are exposed to an MRI environment. PMID- 20353964 TI - Femoral vein implantation with subclavian vein pullthrough for left ventricular lead placement. AB - Variations of coronary sinus anatomy can make a superior approach difficult or even impossible for left ventricular (LV) lead delivery. We describe a new technique in which the LV lead was placed in a cardiac vein via the right femoral vein and then pulled up through the venous circulation to the subclavian vein and a conventionally sited generator. PMID- 20353965 TI - Electrocardiographic and further predictors for permanent pacemaker requirement after transcatheter aortic valve implantation. AB - The objective of this study was to identify electrocardiographic (ECG) and further predictors for atrioventricular (AV) block with a need for pacemaker (PM) implantation after transcatheter aortic valve implantation (TAVI). Pre- and post procedural ECGs of patients with severe aortic stenosis and ongoing TAVI were investigated in a prospective study. From 50 consecutive patients enrolled in the study (mean age 80 +/- 6 years, 46% men), 17 (34%) experienced an AV block with subsequent requirement of a permanent PM [16 of 36 (44.4%) with CoreValve System and 1 of 14 (7.1%) with Edwards Sapiens System]. In patients with right bundle branch block (RBBB), PM implantation had to be performed more frequently [6 of 6 (100%) with CoreValve System and none with Edwards Sapiens System], P = 0.005. An AV block (Mobitz II second degree and third degree) occurred mostly within the first 24 h (range: Days 0-13) after the index procedure. No recovery of AV conduction with a change in PM indication occurred in a mean follow-up time of 13 +/- 6 days. Our data demonstrate that patients with pre-operative RBBB and those receiving CoreValve prosthesis are at a significantly higher risk for PM implantation after TAVI. Therefore, patients with the presence of RBBB before TAVI may be at lower risk for PM implantation using the Edwards Sapiens System. PMID- 20353966 TI - Impact of symptom control on health-related quality of life in atrial fibrillation patients: the psychologist's viewpoint. PMID- 20353967 TI - Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics. AB - This year in Galveston, Texas, Silvia Pierangeli hosts the 13th International Congress on Antiphospholipid Antibodies. Twenty-six years after the first antiphospholipid syndrome meeting, the number of interested colleagues has multiplied, and the subject has become more scientifically understood. So also has the clinical picture. In this short contribution, I will highlight a number of clinical observations which may, or may not, contribute to our understanding of antiphospholipid syndrome. PMID- 20353968 TI - The dual role of innate immunity in the antiphospholipid syndrome. AB - The antiphospholipid syndrome (APS), as both a primary syndrome and a syndrome in association with systemic lupus erythematosus (SLE), can be a devastating disease. It is unclear what factors (genetic and/or environmental) lead to the generation of antiphospholipid antibodies (aPL). It is equally unclear why only certain individuals with aPL develop clinical events. We hypothesize that innate immune activation plays a critical role at two distinct stages of APS, namely, the initiation phase, in which aPL first appear, and the effector phase, in which aPL precipitate a thrombotic event. According to the model we propose, aPL alone are insufficient to cause thrombosis and a concomitant trigger of innate immunity, e.g. a toll-like receptor (TLR) ligand, must be present for thrombosis to occur. Here, we discuss our findings that mice immunized with beta(2) glycoprotein I (beta(2)GPI) and lipopolysaccharide (LPS), a TLR ligand, produce high levels of aPL and other SLE-associated autoantibodies, and develop lupus like glomerulonephritis. We also discuss our data showing that autoantibodies to heat shock protein 60 (HSP60), an 'endogenous TLR ligand', promote thrombus generation in a murine model of arterial injury. Thus, both pathogen-derived TLR ligands (e.g. LPS) and endogenous TLR ligands (e.g. HSP60) may contribute to the pathogenesis of APS. This putative dual role of innate immunity provides new insight into the generation of aPL as well as the enigma of why some individuals with aPL develop APS, while others do not. PMID- 20353969 TI - Autoimmunity, infection and adjuvants. AB - The effect of infection in initiating autoimmune disease has been debated for many years. There are, even now, few instances of a human autoimmune disease clearly caused by prior infection, probably due to the frequent separation in time and space from the clinical outcomes. As our understanding of the immunologic consequences of the infectious process has deepened, we can re-think some of the issues by focusing attention on the varied adjuvant effects of microbial products. We are now able to distinguish some of the critical steps in progression from virus infection to benign autoimmunity to autoimmune disease in an experimental model of myocarditis. Immune regulators, such as cytokines and costimulatory molecules, serve as signposts in the process. The lessons learned may be broadly applicable to autoimmune disorders. PMID- 20353970 TI - Use of monoclonal antibodies to dissect specificity and pathogenesis of antiphospholipid antibodies. AB - Monoclonal antiphospholipid antibodies (aPL) have been utilized to dissect the relationship between their sequence, structure, binding and biological properties relevant to the pathogenesis of the antiphospholipid syndrome. In particular, sequence analysis of aPL has highlighted the clustering of certain amino acid residues in the antigen contact sites of their heavy and light chains. Therefore, these sequence motifs are likely to be important in determining aPL binding properties and their pathogenic effects. Experiments, however, using monoclonal aPL engineered to contain specific point mutations in their sequence which alter their ability to bind relevant antigens have shown that these alterations in binding are not directly mirrored by their pathogenic effects. In this review we focus on work carried out by others and ourselves using monoclonal antibodies with specific binding properties to extend our knowledge of the non-linear structure-binding-function relationship of aPL. PMID- 20353971 TI - Some antiphospholipid antibodies bind to various serine proteases in hemostasis and tip the balance toward hypercoagulant states. AB - The body has an elaborate system that maintains blood circulation and rapidly stops bleeding when vessels are damaged. Abnormalities that disrupt this balance may lead to thrombosis. While beta(2)-glycoprotein I is generally accepted as the major antigen for antiphospholipid antibodies in the antiphospholipid syndrome, our accumulated studies show that some antiphospholipid antibodies bind homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Functionally, some of the protease-reactive antiphospholipid antibodies hinder anticoagulant regulation and resolution of clots, thus tip the balance toward thrombosis. Intriguingly, several serine protease-reactive antiphospholipid antibodies also react with beta(2)-glycoprotein I, and interactions between antiphospholipid antibodies and antigens are cross inhibited, indicating that these antiphospholipid antibodies recognize conformational epitope(s) on beta(2)-glycoprotein I and target serine proteases. Viewed as a whole, these results extend previous reports that antiphospholipid antibodies bind to various hemostasis factors, and provide a new perspective about some antiphospholipid antibodies in terms of their binding specificities and related functional properties in promoting thrombosis. PMID- 20353973 TI - Pathophysiology of beta2-glycoprotein I in antiphospholipid syndrome. AB - Since beta(2)-glycoprotein I (beta(2)GPI) was described as the major antigenic target for antiphospholipid antibodies, many studies have focused their attention to the physiological role of beta(2)GPI and anti-beta(2)GPI antibodies on autoimmune-mediated thrombosis. Studies reporting the physiological role of beta(2)GPI have been numerous, but the exact mechanism of action(s) has yet to be completely determined. beta(2)GPI's epitopes for anti-beta(2)GPI autoantibodies have been characterized, however, not all of the heterogeneous anti-beta(2)GPI antibodies are pathogenic. The pathophysiologic role of beta(2)GPI has been reported in the fields of coagulation, fibrinolysis, angiogenesis, and atherosclerosis. Our understanding of the impact of beta(2)GPI, its metabolites and autoantibodies to beta(2)GPI on these physiological functions may contribute to the development of better therapeutic strategies to treat and prevent autoimmune-mediated atherothrombotic vascular disease. PMID- 20353974 TI - Proteomics in antiphospholipid syndrome: a review. AB - The presence of antiphospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop those clinical features. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Currently, biomarkers which enable one to predict the prognosis of patients with positive aPL are not readily available. Current advances in genomics and proteomics provide the opportunity to discover novel biomarkers based on changes in concentration levels or post-translational modifications of proteins and peptides. These techniques are now being applied in various areas of medicine with very promising results. This review covers recent studies that have used this approach for a better understanding of the pathogenic mechanisms involved in the development of thrombosis in patients with antiphospholipid syndrome (APS). Although, there are very few qualified biomarkers that have arisen as a result of efforts in proteomics, it is expected that these techniques will deliver biomarkers that might ultimately identify different subgroups of APS patients with various prognoses that might have implications with respect to management and prognosis. PMID- 20353972 TI - Role of tissue factor in thrombosis in antiphospholipid antibody syndrome. AB - Antiphospholipid syndrome (APS) is an acquired autoimmune disorder defined by the presence of an antiphospholipid antibody (aPL) and the occurrence of at least one associated clinical condition that includes venous thrombosis, arterial thrombosis or pregnancy morbidity. The aPL detected in APS have long been thought to have a direct prothrombotic effect in vivo. However, the pathophysiology underlying their coagulopathic effect has not been defined. Emerging data suggest a role for the procoagulant protein tissue factor (TF). In this review we provide an overview of TF, describe mouse models used in the evaluation of the role of TF in thrombosis, as well as summarize recent work on TF and APS. PMID- 20353976 TI - Antiphospholipid antibodies and the protein C pathway. AB - Haemostasis is a delicate balance between procoagulant and anticoagulant processes. In the human body usually anticoagulant mechanisms prevail over procoagulant mechanisms, thereby preventing a prothrombotic state. The antiphospholipid syndrome is an example in which this balance is shifted to a more prothrombotic state due to the presence of antiphospholipid antibodies. One of the most extensively proposed pathogenic mechanisms within the antiphospholipid syndrome is the inhibition of protein C by antiphospholipid antibodies. Antiphospholipid antibodies have been described to have different actions on the protein C pathway, for example decreasing protein C and/or S plasma levels, inducing increased resistance against activated protein C and lowering thrombin levels (resulting in an impaired protein C activation). This review briefly discusses the actions of protein C in human body but mainly focuses on the effects of antiphospholipid antibodies on the protein C pathway that have been described in literature. PMID- 20353975 TI - The role of LRP8 (ApoER2') in the pathophysiology of the antiphospholipid syndrome. AB - One of the greatest enigmas in thrombosis research is the observation that one can diagnose a person with a thrombotic risk with a prolongation of the clotting time. Our textbooks have taught us that prolongation of clotting correlates with a tendency to bleed. To confuse our textbook knowledge further, the same patients often have a prolonged bleeding time, a diagnostic test to detect a dysfunction in primary haemostasis. In this paper we critically review the literature that tries to explain the contradiction that exists between in-vitro diagnostic tests and the observed clinical manifestations and discuss our current opinion on how antiphospholipid antibodies can disturb the haemostatic balance. PMID- 20353977 TI - Domain I of beta2-glycoprotein I: its role as an epitope and the potential to be developed as a specific target for the treatment of the antiphospholipid syndrome. AB - Antiphospholipid syndrome (APS) represents one of the most common acquired causes of thrombophilia and recurrent miscarriages. The only treatment of proven benefit is anticoagulation, often required at high intensity and life-long duration. This therapy can be associated with side effects such as bleeding and is not always effective. Hence, there remains a need for safer, targeted and ideally more effective therapies. Antiphospholipid antibodies (aPL) are pathogenic and promote thrombosis. Independent groups, including our own, have show that the major epitopes that pathogenic aPL targets lie within domain I of the protein beta2 glycoprotein I (beta2GPI). This review focuses on the evidence presented thus far which characterizes the immunodominant epitopes within domain I, demonstrating that the epitope is a conformational one centred around residues R39-G43 and also involving other residues within domain I, such as residues D8 and D9. The hypothesis is proposed that a recombinant domain I molecule, and a recombinant mutant domain I with enhanced aPL binding properties, may be used as an inhibitor of aPL binding and thus inhibit aPL-induced pathogenicity. In vivo proof-of concept studies within the murine femoral vein injury model are presented supporting this hypothesis, and the rationale as well as potential benefits and problems of employing such an approach to treat APS are discussed. PMID- 20353978 TI - Antiphospholipid syndrome and the brain in pediatric and adult patients. AB - The most common neurological manifestations of antiphospholipid syndrome (APS) in all age-groups include stroke and transient ischemic attacks due to arterial thromboses and cerebral ischemia. Antiphospholipid antibodies may cause additional non-criteria neurological impairments through vascular, neuroinflammatory and direct neuronal effects. Anti-aggregant or anticoagulant therapies are indicated for APS-related ischemic strokes. Treatment regimens for asymptomatic antibody-positive patients and those with refractory or recurrent disease remain controversial. There is scant literature on the epidemiology and therapy of neurological APS manifestations in pediatric patients. Assessments of modifiable cardiovascular and inherited thrombophilia risk factors are essential in patients with APS. There may be a role for novel neuroimaging modalities in quantifying APS-related microstructural brain damage. The clinical utility of statins, antimalarials, angiotensin-converting enzyme inhibitors, and thrombin inhibitors warrant further research. PMID- 20353979 TI - Catastrophic antiphospholipid syndrome (CAPS): update from the 'CAPS Registry'. AB - Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant, its potentially lethal outcome emphasizes its importance in clinical medicine today. However, the rarity of this variant makes it extraordinarily difficult to study in any systematic way. In order to put together all of the published case reports as well as the new diagnosed cases from all over the world, an international registry of patients with catastrophic APS (CAPS Registry) was created in 2000 by the European Forum on Antiphospholipid Antibodies (see http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, it documents the entire clinical, laboratory and therapeutic data of more than 300 patients whose data has been fully registered. PMID- 20353980 TI - Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort. AB - Anti-phospholipid antibodies are common in patients in the Hopkins' Lupus Cohort: 47% have anti-cardiolipin, 32.5% anti-beta(2)-glycoprotein I and 26% lupus anticoagulant (by dRVVT confirmatory testing). Systemic lupus erythematosus patients with the lupus anticoagulant at baseline have a 50% chance of a deep venous thrombosis/pulmonary embolus in the next 20 years. Anti-phospholipid antibodies differ in their association with thrombosis: the lupus anticoagulant is most strongly associated with arterial and venous thrombosis and is the only anti-phospholipid antibody associated with myocardial infarction. Anti phospholipid antibodies are not associated with atherosclerosis. PMID- 20353981 TI - Non-criteria manifestations of antiphospholipid syndrome. AB - Only few studies have addressed the pathogenesis and treatment of the non criteria manifestations of antiphospholipid antibodies (aPL) such as thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction, skin ulcers, or diffuse pulmonary hemorrhage. There is no consensus on the management of these manifestations; they may occur despite full-dose anticoagulation or may not improve if anticoagulation is initiated after their discovery. This brief review may help physicians in the management of the non-criteria manifestations of aPL. PMID- 20353982 TI - Antiphospholipid syndrome: critical analysis of the diagnostic path. AB - Antiphospholipid syndrome (APS) is diagnosed in the presence of vascular thrombosis or pregnancy morbidity occurring in patients with circulating antiphospholipid antibodies (lupus anticoagulant [LA] and/or IgG/IgM anticardiolipin [aCL] and/or IgG/IgM anti-beta2glycoprotein I [abeta2GPI] antibodies). Each test may identify different autoantibodies; a single test makes the diagnosis possible when positive on two or more occasions at least 12 weeks apart. However, single test positivity may be unrelated to pathogenic antibodies, which are now considered to be a subclass of abeta2GPI antibodies directed against the domain I of this protein. Conversely, all three positive tests identify a single class of abeta2GPI antibodies, thus identifying high-risk patients with APS. PMID- 20353983 TI - Antiphospholipid antibody profile: implications for the evaluation and management of patients. AB - According to the classification criteria of antiphospholipid syndrome, lupus anticoagulant, anticardiolipin and anti-beta(2) glycoprotein I antibody assays are independent risk factors for the occurrence of vascular thrombosis and pregnancy loss. However, it is generally accepted that patients carrying multiple positivity have more a severe disease and higher recurrence rate despite treatment. On the other hand, the diagnostic value of a positive result in one only assay is more controversial, particularly in the presence of clinical manifestations such as deep vein thrombosis or early miscarriages, which are rather common in the general population. In this review we speculate on current and future strategies to interpret different antiphospholipid antibody profiles in the clinical practice. PMID- 20353984 TI - Antiprothrombin antibody: why do we need more assays? AB - Anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (beta(2)GPI) antibodies and lupus anticoagulant (LA) are the only laboratory tests considered within the revised criteria for the classification of the antiphospholipid syndrome (APS). Recently, the significance to assay the antibodies against phosphatidylserine-prothrombin complex (aPS/PT) has been discussed, and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. The sensitivity and specificity of aPS/PT for the diagnosis of APS were assessed in a population of patients with a variety of autoimmune disorders. The aCL and aPS/PT have similar diagnostic value for APS, and most of APS patients with aPS/PT had positive LA. Therefore, aPS/PT should be further explored, not only for research purposes, but also as a candidate for one of the enzyme-linked immunosorbent assay (ELISA)-based confirmatory test for APS associated LA. PMID- 20353985 TI - Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice. AB - Antiphospholipid antibodies (aPL) are best considered as risk factors. aPL are not diagnostic tests and considering them as such can be misleading and may direct attention away from the more important clinical issue of risk modification and management. When considering aPL as risk factors, quantitative aPL tests such enzyme-linked immunosorbent assay (ELISA) for anticardiolipin (aCL) and anti beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies, should be interpreted carefully. Risk for clinical manifestations appears to be associated with moderate to high levels of these autoantibodies. Lower levels may be statistically abnormal compared with a control population, but may not be associated with the risk of thrombosis or pregnancy loss. Lupus anticoagulants (LA) are generally thought to be more strongly associated with the risk of clinical manifestation of antiphospholipid syndrome (APS) than aCL and anti beta(2)GPI antibodies. One reason for the stronger association may be related to patients' antibody titers. LA assays are not very analytically sensitive, i.e. a relatively high concentration of antibodies is required to prolong the clotting time in these tests. Thus, the presence of LA indicates a high titer of aPL and this, rather than the intrinsic functional characteristics of LA antibodies, may explain the high risk of clinical manifestations associated with LA. PMID- 20353986 TI - Obstetric antiphospholipid syndrome: current uncertainties should guide our way. AB - The subject of obstetric antiphospholipid syndrome (APS) has been reviewed dozens of times, and there is little doubt that the international APS community has done well in bringing APS to the attention of clinicians around the world. However, the evolution of clinical practice, at least in the US, also has convinced us that our field would benefit from further clinical study. For example, the number of women diagnosed with 'APS', but who do not meet the revised Sapporo criteria, seems to have increased. It is now common practice for women with recurrent miscarriage or prior fetal death to be treated with heparin, even in the presence of indeterminate or low titer antiphospholipid antibody (aPL) levels and even after only one positive test. In part, this common practice derives from confusion on the part of many clinicians and patients regarding the diagnosis of APS as well as the clinical and laboratory criteria for the syndrome. In part, this derives from the common practice of so-called 'empiric treatment' in US reproductive medicine, often driven as much by patients as by clinicians. This brief commentary focuses on areas of uncertainty that we see as deserving of new or renewed study for the sake of improving our understanding of APS and best patient care. PMID- 20353987 TI - Anti-phospholipid antibody mediated fetal loss: still an open question from a pathogenic point of view. AB - Antiphospholipid antibodies (aPL) are associated with recurrent miscarriages and pregnancy complications, however their pathogenic mechanisms are still matter of research. Thrombotic events at the placental level cannot explain all of the clinical manifestations. It has been suggested that aPL may be responsible for a local acute inflammatory response mediated by complement activation and neutrophil infiltration eventually leading to fetal loss. However histological and immunohistological studies on human placental samples do support such a mechanism only in part and with no any clear relationship with the pregnancy outcome. A direct effect of aPL on both maternal and fetal placental tissues has been reported through the reactivity of the antibodies with beta2 glycoprotein I (beta2GPI) expressed on the cell membranes. These events do not require an inflammatory response and can be in part related to the inhibition of growth factors favouring a physiological placentation. Understanding the different pathogenic mechanisms of aPL-associated miscarriages may help in improving our therapeutic approach particularly in recurrent cases not responsive to the usual treatment. PMID- 20353988 TI - Obstetric antiphospholipid syndrome: still a challenge. AB - Obstetric complications such as fetal death, premature delivery, preeclampsia and recurrent abortions (since chromosomal or anatomic defects have been excluded) are characteristic manifestations of antiphospholipid syndrome (APS). They can occur in patients with known APS with previous arterial or venous events in any tissue or organ, or be its first and only manifestation. Pregnancy in a patient with APS is considered high risk and the full prenatal clinical follow-up must be carried with this in mind, eliminating or minimizing concomitant thrombotic risk factors. PMID- 20353989 TI - The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: role in pregnancy losses and thrombosis. AB - Annexin A5 (AnxA5) binds to phospholipid bilayers, forming two-dimensional crystals that block the phospholipids from availability for coagulation enzyme reactions. Antiphospholipid (aPL) antibodies cause gaps in the ordered crystallization of AnxA5 which expose phospholipids and thereby accelerate blood coagulation reactions. The aPL antibody-mediated disruption of AnxA5 crystallization has been confirmed on artificial phospholipid bilayers and on cell membranes including endothelial cells, placental trophoblasts and platelets. Recently, we reported that hydroxychloroquine, a synthetic antimalarial drug, can reverse this antibody-mediated process through two mechanisms: (1) by inhibiting the formation of aPL IgG-beta2glycoprotein I complexes; and (2) by promoting the formation of a second layer of AnxA5 crystal 'patches' over areas where the immune complexes had disrupted AnxA5 crystallization. In another translational application, we have developed a mechanistic assay that reports resistance to AnxA5 anticoagulant activity in plasmas of patients with aPL antibodies. AnxA5 resistance may identify a subset of aPL syndrome patients for whom this is a mechanism for pregnancy losses and thrombosis. The elucidation of aPL-mediated mechanisms for thrombosis and pregnancy complications may open new paths towards addressing this disorder with targeted treatments and mechanistic assays. PMID- 20353990 TI - Towards evidence-based treatment of thrombotic antiphospholipid syndrome. AB - Thrombosis in the presence of persistently positive tests for antiphospholipid antibodies is termed thrombotic antiphospholipid syndrome (APS). At present, 'standard' secondary thromboprophylaxis in thrombotic APS is treatment with moderate intensity oral anticoagulants for life after a first venous thrombosis and with high intensity oral anticoagulation after non-embolic ischaemic stroke. These recommendations differ from those applied in the general population, where a restricted period of anticoagulation is common practice after venous thrombosis and antiplatelet drugs are the first choice after ischaemic stroke. From an extensive literature review we conclude that the available data are insufficient to apply a different strategy for secondary thromboprophylaxis in patients with thrombotic APS than the one that holds for the general population. PMID- 20353991 TI - Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? AB - Persistently positive antiphospholipid antibodies in association with thromboses and/or pregnancy morbidity is the hallmark of the antiphospholipid syndrome. The management of antiphospholipid antibody-positive patients has been focused on utilizing anti-thrombotic medications such as heparin or warfarin. Given that our understanding of the molecular mechanisms of antiphospholipid antibody-mediated thrombosis has been growing, it is highly likely that the current 'anti thrombotic' approach to these patients will be replaced by an 'immunomodulatory' approach in the near future. This review article will address the experimental and/or clinical evidence behind some of these potential 'immunomodulatory' approaches (tissue factor inhibition, P38 mitogen-activated protein kinase inhibition, nuclear factor-kappaB inhibition, platelet glycoprotein receptor inhibition, hydroxychloroquine, statins, inhibition of beta(2)GPI and/or anti beta(2)GPI binding to target cells, complement inhibition, and B cell inhibition) in antiphospholipid syndrome. PMID- 20353992 TI - Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? AB - Anticoagulation with oral vitamin K antagonists (VKA) is the mainstay of the treatment of venous and/or arterial thromboembolism in patients with antiphospholipid syndrome (APS), although the optimal intensity of anticoagulation remains controversial. The limitations of existing anticoagulants have driven a search for novel agents. Dabigatran etexilate (Pradaxa), a direct thrombin inhibitor (DTI), and rivaroxaban (Xarelto), the first in a new class of drugs, the oral direct factor Xa (FXa) inhibitors, are both fixed-dose orally administered agents. They are now licensed in the UK and Europe for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Prospective randomized clinical trials suggest that these agents, and also apixaban, a further oral direct anti-Xa inhibitor, may have potential in other areas including the treatment of acute VTE, prevention of stroke or systemic embolism in patients with atrial fibrillation (AF) and acute coronary syndromes. Here, we summarize current indications for these agents and address the potential for their use in patients with thrombotic APS. PMID- 20353996 TI - TAF4b and Jun/activating protein-1 collaborate to regulate the expression of integrin alpha6 and cancer cell migration properties. AB - The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific interactions between Jun family members and TATA box binding protein-associated factors (TAF) in colon HT29 adenocarcinoma cells. Particularly, TAF4b and c-Jun were found to colocalize and interact in the nucleus of advanced carcinoma cells and in cells with epithelial-to-mesenchymal transition (EMT) characteristics. TAF4b was found to specifically regulate the AP-1 target gene involved in EMT integrin alpha6, thus altering related cellular properties such as migration potential. Using a chromatin immunoprecipitation approach in colon adenocarcinoma cell lines, we further identified a synergistic role for TAF4b and c-Jun and other AP-1 family members on the promoter of integrin alpha6, underlining the existence of a specific mechanism related to gene expression control. We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT. PMID- 20353997 TI - Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line. AB - Erythropoietin (Epo), the major regulator of erythropoiesis, and its cognate receptor (EpoR) are also expressed in nonerythroid tissues, including tumors. Clinical studies have highlighted the potential adverse effects of erythropoiesis stimulating agents when used to treat cancer-related anemia. We assessed the ability of EpoR to enhance tumor growth and invasiveness following Epo stimulation. A benign noninvasive rat mammary cell line, Rama 37, was used as a model system. Cell signaling and malignant cell behavior were compared between parental Rama 37 cells, which express few or no endogenous EpoRs, and a modified cell line stably transfected with human EpoR (Rama 37-28). The incubation of Rama 37-28 cells with pharmacologic levels of Epo led to the rapid and sustained increases in phosphorylation of signal transducers and activators of transcription 5, Akt, and extracellular signal-regulated kinase. The activation of these signaling pathways significantly increased invasion, migration, adhesion, and colony formation. The Epo-induced invasion capacity of Rama 37-28 cells was reduced by the small interfering RNA-mediated knockdown of EpoR mRNA levels and by inhibitors of the phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways with adhesion also reduced by Janus-activated kinase 2/signal transducers and activators of transcription 5 inhibition. These data show that Epo induces phenotypic changes in the behavior of breast cancer cell lines and establishes links between individual cell signaling pathways and the potential for cancer spread. PMID- 20353999 TI - The microRNA profile of prostate carcinoma obtained by deep sequencing. AB - Prostate cancer is a leading cause of tumor mortality. To characterize the underlying molecular mechanisms, we have compared the microRNA (miRNA) profile of primary prostate cancers and noncancer prostate tissues using deep sequencing. MiRNAs are small noncoding RNAs of 21 to 25 nucleotides that regulate gene expression through the inhibition of protein synthesis. We find that 33 miRNAs were upregulated or downregulated >1.5-fold. The deregulation of selected miRNAs was confirmed by both Northern blotting and quantitative reverse transcription PCR in established prostate cancer cell lines and clinical tissue samples. A computational search indicated the 3'-untranslated region (UTR) of the mRNA for myosin VI (MYO6) as a potential target for both miR-143 and miR-145, the expression of which was reduced in the tumor tissues. Upregulation of myosin VI in prostate cancer was previously shown by immunohistochemistry. The level of MYO6 mRNA was significantly induced in all primary tumor tissues compared with the nontumor tissue from the same patient. This finding was matched to the upregulation of myosin VI in established prostate cancer cell lines. In luciferase reporter analysis, we find a significant negative regulatory effect on the MYO6 3'UTR by both miR-143 and miR-145. Mutation of the potential binding sites for miR-143 and miR-145 in the MYO6 3'UTR resulted in a loss of responsiveness to the corresponding miRNA. Our data indicate that miR-143 and miR 145 are involved in the regulation of MYO6 expression and possibly in the development of prostate cancer. PMID- 20353998 TI - Prostaglandin E2 promotes lung cancer cell migration via EP4-betaArrestin1-c-Src signalsome. AB - Many human cancers express elevated levels of cyclooxygenase-2 (COX-2), an enzyme responsible for the biosynthesis of prostaglandins. Available clinical data establish the protective effect of COX-2 inhibition on human cancer progression. However, despite these encouraging outcomes, the appearance of unwanted side effects remains a major hurdle for the general application of COX-2 inhibitors as effective cancer drugs. Hence, a better understanding of the molecular signals downstream of COX-2 is needed for the elucidation of drug targets that may improve cancer therapy. Here, we show that the COX-2 product prostaglandin E(2) (PGE(2)) acts on cognate receptor EP4 to promote the migration of A549 lung cancer cells. Treatment with PGE(2) enhances tyrosine kinase c-Src activation, and blockade of c-Src activity represses the PGE(2)-mediated lung cancer cell migration. PGE(2) affects target cells by activating four receptors named EP1 to EP4. Use of EP subtype-selective ligand agonists suggested that EP4 mediates prostaglandin-induced A549 lung cancer cell migration, and this conclusion was confirmed using a short hairpin RNA approach to specifically knock down EP4 expression. Proximal EP4 effectors include heterotrimeric Gs and betaArrestin proteins. Knockdown of betaArrestin1 expression with shRNA significantly impaired the PGE(2)-induced c-Src activation and cell migration. Together, these results support the idea that increased expression of the COX-2 product PGE(2) in the lung tumor microenvironment may initiate a mitogenic signaling cascade composed of EP4, betaArrestin1, and c-Src which mediates cancer cell migration. Selective targeting of EP4 with a ligand antagonist may provide an efficient approach to better manage patients with advanced lung cancer. PMID- 20354000 TI - Upregulation of DNA methyltransferase-mediated gene silencing, anchorage independent growth, and migration of colon cancer cells by interleukin-6. AB - Inflammatory bowel disease is characterized by chronic inflammation which predisposes to colorectal cancer. The mechanisms by which inflammation promotes tumorigenesis are not fully known. We aimed to investigate the links between colonic inflammation and tumorigenesis via epigenetic gene silencing. Colon cancer specimens were assessed for the expression of DNA methyltransferase-1 (DNMT-1) using immunohistochemistry. Colorectal carcinoma cell lines were assessed for DNMT1 expression, methylcytosine content, promoter methylation, gene expression, and tumorigenesis in response to interleukin (IL)-6. DNMT1 was expressed at higher levels in both the peritumoral stroma and tumor in inflammatory bowel disease-associated cancers compared with sporadic colon cancers. IL-6 treatment of colon cancer cells resulted in an increase in DNMT1 expression, independent of de novo gene expression. IL-6 increased the methylation of promoter regions of genes associated with tumor suppression, adhesion, and apoptosis resistance. Expression of a subset of these genes was downregulated by IL-6, an effect that was prevented by preincubation with 5 azadeoxycytidine, a DNMT1 inhibitor. Anchorage-independent growth and migration of colon cancer cells was also increased by IL-6 in a 5-azadeoxycytidine sensitive manner. Our results indicate that DNMT-mediated gene silencing may play a role in inflammation-associated colon tumorigenesis. PMID- 20354001 TI - Angiogenesis in glioblastoma: just another moving target? PMID- 20354002 TI - Dynamic functional reorganization of the motor execution network after stroke. AB - Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity. PMID- 20354003 TI - T cells can mediate viral clearance from ependyma but not from brain parenchyma in a major histocompatibility class I- and perforin-independent manner. AB - Viral infection of the central nervous system can lead to disability and death. Yet the majority of viral infections with central nervous system involvement resolve with only mild clinical manifestations, if any. This is generally attributed to efficient elimination of the infection from the brain coverings, i.e. the meninges, ependyma and chorioplexus, which are the primary targets of haematogeneous viral spread. How the immune system is able to purge these structures from viral infection with only minimal detrimental effects is still poorly understood. In the present work we studied how an attenuated lymphocytic choriomeningitis virus can be cleared from the central nervous system in the absence of overt disease. We show that elimination of the virus from brain ependyma, but not from brain parenchyma, could be achieved by a T cell-dependent mechanism operating independently of major histocompatibility class I antigens and perforin. Considering that cytotoxic T lymphocyte-mediated cytotoxicity is a leading cause of viral immunopathology and tissue damage, our findings may explain why the most common viral intruders of the central nervous system rarely represent a serious threat to our health. PMID- 20354006 TI - Autonomic nervous system state: the effect of general anaesthesia and bilateral tonsillectomy after unilateral infiltration of lidocaine. AB - BACKGROUND: Autonomic nervous system (ANS) sensitively responds to intraoperative stress. Several indices characterizing the state and responses of autonomic signs to nociceptive stimuli have been introduced. This study evaluated the behaviour of ANS descriptors after induction, before and during tracheal intubation, and during bilateral tonsillectomies after random and blinded unilateral infiltration of lidocaine 1% until emergence from anaesthesia. METHODS: Twelve patients undergoing bilateral tonsillectomy were anaesthetized with fentanyl and propofol (induction) and sevoflurane (maintenance). All patients were monitored throughout anaesthesia for middle finger temperature, non-invasive arterial pressure, heart rate (HR) and pulse rate (PR), state entropy (SE) and response entropy (RE), and surgical pleth index (SPI). New parameters complementing the above and characterizing the ANS state (ANSS) and responses are pulse-to-pulse interval (PPI), pulse plethysmographic amplitude (PPGA), ANSS, and an index based on maximal ANSS for the subject (ANSSI). Serial data were stored as 10 s averages into a laptop computer. RESULTS: Anaesthesia induction was associated with an increase in finger temperature to >30 degrees C within 10 min, whereas PPGA increased to their maximum levels within 5 min. Laryngoscopy and intubation were associated with transient autonomic responses in most patients. All autonomic signs indicated statistically significant sympathetic activation during saline infiltrated tonsillectomies when compared with lidocaine-infiltrated sides (P<0001). Hypnotic measures (SE and RE) and finger temperatures did not differ between the sides. CONCLUSIONS: HR, PPI, PPGA, ANSS, ANSSI, SPI, and RE-SE detect autonomic responses to nociceptive stimuli and differentiate between tonsillectomies on locally anaesthetized tonsils from controls. PMID- 20354005 TI - Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation. AB - Trypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface anchored trans-sialidase. This enzyme transfers sialic acid residues from the host's sialylglycoconjugates to the parasite's galactosylglycoconjugates. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. A major obstacle to understand these events is the difficulty to identify the transferred sialic acid among all those naturally occurring on the cell surface. Here, we report the use of azido-modified unnatural sialic acid to identify those molecules that act as cell surface acceptors of the sialyl residue in the trans-sialidase-catalyzed reaction, which might then be involved in the immune alterations induced. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. In both leukocyte populations, the main proteins labeled were identified as different CD45 isoforms. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Nevertheless, CD45 remained to be the main acceptor. Mass spectrometry assays allowed us to identify other acceptors, mainly integrins. The findings reported here provide a molecular basis to understand the abnormalities induced in the immune system by the trans-sialidase during T. cruzi infection. PMID- 20354007 TI - Effect of sleep deprivation on labour epidural catheter placement. AB - BACKGROUND: Epidural catheter insertion for labour analgesia is an invasive procedure with potential serious complications, often performed by a sleep deprived clinician. The aim of this study was to examine the effects of sleep deprivation on physicians of variable levels of experience performing this procedural skill in the clinical setting. METHODS: After institutional review board approval, anaesthetists of three levels of experience were recruited: novice residents (<30 epidurals, n=9), experienced residents (>100 epidurals, n=8), and attending anaesthetists (>500 epidurals, n=12). All participants were measured twice, rested and sleep deprived in a random order while performing a labour epidural for analgesia. Our primary outcome measures were scores achieved on the Imperial College Surgical Assessment Device (ICSAD) (measuring path length, number of movements, and time), task-specific checklist (CL), and global rating scale (GRS). Sleep deprivation was documented by the ActiGraph and Epworth sleepiness scale. RESULTS: Subjects were adequately sleep deprived for their sleep deprivation observation. Data were analysed with a two-way mixed design analysis of variance. No significant difference in the effect of sleep deprivation on performance was detected between the groups on the ICSAD measures of movement (P=0.86), path length (P=0.79), and time (P=0.80), or for the CL (P=0.65), and GRS (P=0.86). CONCLUSIONS: The performance of this procedural skill in a clinical setting does not seem to be affected by sleep deprivation irrespective of the level of experience. PMID- 20354008 TI - Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population. AB - BACKGROUND: Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a primary pain-sensing relay at peripheral sensory nerve endings and is also widespread in the brain, where it is implicated in neurodegeneration. Previous studies of TRPV1 neurotoxicity have utilized heterogeneous receptor populations, non-selective ligands, or non-neuronal cell types. Here, we explored the pharmacology of TRPV1-induced cytotoxicity in a homogeneous, neurone-like cellular environment. METHODS: Cell death was examined in a human neurone-like cell line, stably expressing recombinant human TRPV1. Cytotoxicity was quantified in terms of nuclear morphology and mitochondrial complex II activity. Immunocytochemical markers of apoptotic cell death were also examined. RESULTS: The TRPV1-selective agonist capsaicin, and the endovanilloids anandamide and N arachidonoyl-dopamine (NADA), induced TRPV1-dependent delayed cell death in a concentration- and time-dependent manner. Capsaicin exposure time was significantly correlated with potency (r(2)=0.91, P=0.01). Release of cytochrome c from mitochondria, activation of caspase-3, and condensed nuclear chromatin were evident 6 h after capsaicin exposure, but cytotoxicity was unaffected by a pan-caspase inhibitor (zVAD-fmk, 50 microM). CONCLUSIONS: We conclude that capsaicin, anandamide, and NADA can initiate TRPV1-dependent delayed cell death in neurone-like cells. This is an apoptosis-like process, but independent of caspase activity. PMID- 20354004 TI - Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis. AB - Autoreactive CD4+ T lymphocytes play a vital role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Since the discovery of T helper 17 cells, there is an ongoing debate whether T helper 1, T helper 17 or both subtypes of T lymphocytes are important for the initiation of autoimmune neuroinflammation. We examined peripheral blood CD4+ cells from patients with active and stable relapsing-remitting multiple sclerosis, and used mice with conditional deletion or over-expression of the transforming growth factor-beta inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation. We found that Smad7 is up regulated in peripheral CD4+ cells from patients with multiple sclerosis during relapse but not remission, and that expression of Smad7 strongly correlates with T-bet, a transcription factor defining T helper 1 responses. Concordantly, mice with transgenic over-expression of Smad7 in T cells developed an enhanced disease course during experimental autoimmune encephalomyelitis, accompanied by elevated infiltration of inflammatory cells and T helper 1 responses in the central nervous system. On the contrary, mice with a T cell-specific deletion of Smad7 had reduced disease and central nervous system inflammation. Lack of Smad7 in T cells blunted T cell proliferation and T helper 1 responses in the periphery but left T helper 17 responses unaltered. Furthermore, frequencies of regulatory T cells were increased in the central nervous system of mice with a T cell-specific deletion and reduced in mice with a T cell-specific over-expression of Smad7. Downstream effects of transforming growth factor-beta on in vitro differentiation of naive T cells to T helper 1, T helper 17 and regulatory T cell phenotypes were enhanced in T cells lacking Smad7. Finally, Smad7 was induced during T helper 1 differentiation and inhibited during T helper 17 differentiation. Taken together, the level of Smad7 in T cells determines T helper 1 polarization and regulates inflammatory cellular responses. Since a Smad7 deletion in T cells leads to immunosuppression, Smad7 may be a potential new therapeutic target in multiple sclerosis. PMID- 20354009 TI - Progesterone decreases sevoflurane requirement in male mice: a dose-response study. AB - BACKGROUND: Progesterone has long been known to have central effects, by reduced anaesthetic requirements as measured by minimum alveolar concentration (MAC) in various settings. However, other studies have contradicted these findings. Therefore, we compared the effect of progesterone on anaesthetic requirements in a mouse model. METHODS: Male C57BL/6 mice were treated with either progesterone (37.5 or 75 mg kg(-1)) or the olive oil vehicle, 1 h before each experiment. Animals were placed in a revolving cylinder (4 rev min(-1)) and supplied with oxygen and stepwise increasing concentrations of sevoflurane. The number of complete rollovers during revolution of the chamber was counted as a measure of anaesthetic requirement. RESULTS: S.C. administration of progesterone 75 mg kg( 1) significantly reduced sevoflurane requirement (P<0.0001). Progesterone 37.5 mg kg(-1) did not change sevoflurane requirement. CONCLUSIONS: We conclude that administration of exogenous progesterone injection at higher concentrations decreases anaesthetic requirement as defined by rolling response. PMID- 20354010 TI - Lung recruitment and positive airway pressure before extubation does not improve oxygenation in the post-anaesthesia care unit: a randomized clinical trial. AB - BACKGROUND: Atelectasis is known to develop during anaesthesia and after operation atelectasis leads to impaired oxygenation. Lung recruitment manoeuvres, positive end-expiratory pressure (PEEP), and continuous positive airway pressure (CPAP) have been proposed for reduction of atelectasis but their benefits have not been shown to persist after operation. We proposed that a combination of these techniques before extubation would improve oxygenation after operation. METHODS: Adult patients undergoing elective surgery requiring tracheal intubation and an arterial catheter were randomized to receive either: a lung recruitment manoeuvre of 40 cm H(2)O for 15 s, 30 min before the end of anaesthesia, followed by 10 cm H(2)O of PEEP and then 10 cm H(2)O of CPAP from return of spontaneous breathing until extubation; or no lung recruitment manoeuvre, 50 years in a derivation set (data from two multicentre cohort studies), based on receiver operating characteristics (ROC) curves. This cut-off value was then validated with two independent validation datasets. MAIN OUTCOME MEASURES: The proportion of patients in the validation cohorts with a negative D dimer test, the proportion in whom pulmonary embolism could be excluded, and the false negative rates. RESULTS: The new D-dimer cut-off value was defined as (patient's agex10) microg/l in patients aged >50. In 1331 patients in the derivation set with an "unlikely" score from clinical probability assessment, pulmonary embolism could be excluded in 42% with the new cut-off value versus 36% with the old cut-off value (<500 microg/l). In the two validation sets, the increase in the proportion of patients with a D-dimer below the new cut-off value compared with the old value was 5% and 6%. This absolute increase was largest among patients aged >70 years, ranging from 13% to 16% in the three datasets. The failure rates (all ages) were 0.2% (95% CI 0% to 1.0%) in the derivation set and 0.6% (0.3% to 1.3%) and 0.3% (0.1% to 1.1%) in the two validation sets. CONCLUSIONS: The age adjusted D-dimer cut-off point, combined with clinical probability, greatly increased the proportion of older patients in whom pulmonary embolism could be safely excluded. PMID- 20354013 TI - Markets in health care. Markets will never work. PMID- 20354014 TI - Attempt to introduce smoking ban in public places fails in Poland. PMID- 20354015 TI - Protests follow US Congress's passing of health reform bill. PMID- 20354017 TI - Obama's reform: no cure for what ails us. PMID- 20354019 TI - Sleep apnoea: from person to patient, and back again. PMID- 20354020 TI - Is modern genetics a blind alley? No. PMID- 20354021 TI - Is modern genetics a blind alley? Yes. PMID- 20354022 TI - Europe's opportunity to open up drug regulation. PMID- 20354029 TI - Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. AB - Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present. PMID- 20354024 TI - WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study. AB - OBJECTIVES: To assess the performance of WHO's "Guidelines for care at the first referral level in developing countries" in an area of intense malaria transmission and identify bacterial infections in children with and without malaria. DESIGN: Prospective study. SETTING: District hospital in Muheza, northeast Tanzania. PARTICIPANTS: Children aged 2 months to 13 years admitted to hospital for febrile illness. MAIN OUTCOME MEASURES: Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials. RESULTS: Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent. CONCLUSIONS: In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality. PMID- 20354030 TI - Association of obesity and survival in systolic heart failure after acute myocardial infarction: potential confounding by age. AB - AIMS: To determine the association between obesity and outcomes in post-acute myocardial infarction (AMI) patients with systolic heart failure (HF). METHODS AND RESULTS: Of the 6632 Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) participants, 6611 had data on baseline body mass index (BMI) and 6561 had BMI > or = 18.5 kg/m(2). Of these, 1573 were obese (BMI > or = 30 kg/m(2)) and 4988 were non-obese (BMI 18.5-29.9 kg/m(2)). Propensity scores for obesity, estimated for each patient, were used to assemble a cohort of 1519 pairs of obese and non-obese patients who were balanced on 65 baseline characteristics. All-cause mortality occurred in 13.7 and 13.8% of matched obese and non-obese patients, respectively, during 16 months of median follow-up [matched hazard ratio (HR) for obesity 0.98; 95% confidence interval (CI) 0.79-1.21; P = 0.831]. Before matching, the obese group was younger (mean age, 62 vs. 64 years; P < 0.0001) and had more women (37 vs. 26%; P < 0.0001). The paradoxical pre-match association between obesity and reduced mortality (unadjusted HR 0.82; 95% CI 0.70-0.95; P = 0.008) disappeared when adjusted for age alone (age-adjusted HR 0.91; 95% CI 0.78-1.06; P = 0.206) but not for gender alone (gender-adjusted HR 0.79; 95% CI 0.68-0.92; P = 0.003). Obesity had no association with mortality in 1573 pairs of age-matched obese and non-obese patients (age-adjusted HR 0.94; 95% CI 0.77-1.13; P = 0.484). CONCLUSION: In post AMI patients with systolic HF, obesity provides no independent intrinsic survival benefit. The paradoxical unadjusted survival associated with obesity is largely explained by the younger age of obese patients. PMID- 20354031 TI - Does cognitive impairment predict poor self-care in patients with heart failure? AB - AIMS: Cognitive impairment occurs often in patients with chronic heart failure (CHF) and may contribute to sub-optimal self-care. This study aimed to test the impact of cognitive impairment on self-care. METHODS AND RESULTS: In 93 consecutive patients hospitalized with CHF, self-care (Self-Care of Heart Failure Index) was assessed. Multiple regression analysis was used to test a model of variables hypothesized to predict self-care maintenance, management, and confidence. Variables in the model were mild cognitive impairment (MCI; Mini Mental State Exam and Montreal Cognitive Assessment), depressive symptoms (Cardiac Depression Scale), age, gender, social isolation, education level, new diagnosis, and co-morbid illnesses. Sixty-eight patients (75%) were coded as having MCI and had significantly lower self-care management (eta(2)= 0.07, P < 0.01) and self-confidence scores (eta(2)= 0.05, P < 0.05). In multivariate analysis, MCI, co-morbidity index, and NYHA class III or IV explained 20% of the variance in self-care management (P < 0.01); MCI made the largest contribution explaining 9% of the variance. Increasing age and symptoms of depression explained 13% of the variance in self-care confidence scores (P < 0.01). CONCLUSION: Cognitive impairment, a hidden co-morbidity, may impede patients' ability to make appropriate self-care decisions. Screening for MCI may alert health professionals to those at greater risk of failed self-care. PMID- 20354032 TI - Improved survival with bisoprolol in patients with heart failure and renal impairment: an analysis of the cardiac insufficiency bisoprolol study II (CIBIS II) trial. AB - AIMS: Information on the effectiveness of beta-blockade in patients with heart failure (HF) and concomitant renal impairment is scarce and beta-blockers are underutilized in these patients. METHODS AND RESULTS: The Cockcroft-Gault formula normalized for body surface-area was used to estimate renal function (eGFR(BSA)) in 2622 patients with HF, left ventricular ejection fraction < or =35%, New York Heart Association class III/IV and serum creatinine <300 micromol/L (3.4 mg/dL) in the second Cardiac Insufficiency Bisoprolol Study II. Patients were divided into four sub-groups according to baseline eGFR(BSA) (<45, 45-60, 60-75 and > or =75 mL/min per 1.73 m(2)). Cox proportional-hazards models adjusted for pre specified confounders were used to assess the effect of bisoprolol and potential heterogeneity of effect across the eGFR(BSA) sub-groups. Older age, female-sex, diabetes and ischaemic-aetiology were more common in those with reduced eGFR(BSA). The hazard associated with bisoprolol use for all-cause mortality, the composite of all-cause mortality or HF-hospitalization and HF-hospitalization alone was consistently <1.0 across eGFR(BSA) categories with no treatment by renal-function interaction (P = 0.81, P = 0.66, P = 0.71, respectively). The rate of bisoprolol discontinuation was higher in patients with eGFR(BSA) < 45 mL/min per 1.73 m(2). Nevertheless the absolute benefit of bisoprolol was greater for patients with chronic kidney disease compared with those without. CONCLUSION: The beneficial effects of bisoprolol on mortality and hospitalization for worsening heart-failure were not modified by baseline eGFR(BSA). Renal impairment should not prevent the use of bisoprolol in patients with HF. PMID- 20354033 TI - Endothelial dysfunction, measured by reactive hyperaemia using strain-gauge plethysmography, is an independent predictor of adverse outcome in heart failure. AB - AIMS: In congestive heart failure (CHF), arterial response is regulated by endothelial molecules. The aim of this study was to evaluate whether endothelial dysfunction (ED) was a predictor of outcome in a cohort of patients with heart failure. METHODS AND RESULTS: Endothelial function was assessed in 242 patients with CHF by forearm reactive hyperaemia measured with intermittent venous occlusion plethysmography using a mercury strain gauge. The main endpoints were: 'total events' (death, heart attack, angina, stroke, NYHA class IV, or hospitalization due to heart failure) analysed using Cox regression for repeated events and 'death'. Patients were followed-up for 5 years. Post-hyperaemia forearm blood flow (PHFABF) was an independent predictor of total events [P = 0.01; hazard ratio [Exp(B)] 0.665, standard error (SE) 0.182]. Risk stratification by basal forearm blood flow (BFABF) showed that patients with basal blood flow above the median (3.03 mL min(-1) 100 mL(-1)) benefited from an increase in PHFABF, whereas in patients with a BFABF below the median, the increase in PHFABF did not diminish the risk of events. There was no relation between variations in PHFABF and death. CONCLUSION: Post-hyperaemia forearm blood flow, as a measure of ED, is an independent predictor of major events in patients with CHF. A BFABF below the median is more predictive of an increased risk of complications. PMID- 20354034 TI - Surgical resection of a giant pericardial cyst showing a rapidly growing feature. AB - This report presents an extremely rare case of a rapidly growing giant pericardial cyst which was surgically removed 20 years after the first detection. A 38-year-old asymptomatic male was referred because of rapidly growing mass on the right diaphragm. This lesion was detected about 20 years earlier and checked by a chest roentgenogram once a year. However, this lesion showed rapid growth over the last year, therefore surgical removal was performed. A pathological examination revealed this lesion as a giant pericardial cyst without inflammatory, hemorrhage or malignant cells. Therefore, there was no pathological explanation for the rapid growth of this cyst. In conclusion, general thoracic surgeons should be aware of the possibility of rapid growth, even if the diagnosis is a pericardial cyst. PMID- 20354035 TI - Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass. AB - Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB. PMID- 20354036 TI - Seal properties of TachoSil: in vitro hemodynamic measurements. AB - Fibrin glue products and collagen patches are frequently used as a sealing product, preventing surgical side bleedings. This is especially true in the field of cardiovascular surgery, where increasing numbers of patients are being operated with antiplatelet and anticoagulation therapy. The aim of this report was, in an in vitro hemodynamic setting, to examine the sealant properties of the TachoSil (Nycomed Pharma, Linz, Austria) patch. Burst pressure and normal force of 15 TachoSil sealed defects were measured. This was determined in a closed hydraulic system. Mean burst pressure load for a 5-mm defect was 69+/-11.4 mmHg; for a 7-mm defect was 63+/-16 mmHg; and, 62+/-16 mmHg for the defect with a diameter of 10 mm (P>0.05). The mean calculated normal force was as follows: 0.91+/-0.15 N for the 5 mm defect, 6.5+/-1.6 N for the 7 mm, and 8.1+/-0.75 N for the 10 mm defect. The TachoSil patch has the capability to seal small defects. However, at the larger defects the seal character was significantly reduced. These results suggest that the device may be a good alternative for hemostasis for small defects. The capacity to curtail or stop hemorrhage at the larger defects is unlikely. PMID- 20354037 TI - In elderly patients with lung cancer is resection justified in terms of morbidity, mortality and residual quality of life? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: In [patients over 70 years of age with lung cancer] is [lung resection] when compared with [non-surgical treatment] justified in terms of [postoperative morbidity, mortality and quality of life]? Altogether more than 297 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that patients over 70 years of age undergoing anatomical lung resection respond as well as younger patients in terms of morbidity, mortality and residual quality of life (QoL). Collective analysis of the papers reveals no significant difference in five-year survival rates following surgery for early stage disease (stage I non-small cell lung cancer: <70 years; 69-77%, >70 years; 59-78%), although, elderly patients currently receive far higher rates of palliative care (30-47% in patients 65-70 years vs. 8% in patients under 65 years). Additionally, 30-day mortality rates (5.7% <70 years vs. 1.3-3.3% >70 years), length of hospital stay [1.3 days vs. 1 day (video-assisted mini-thoracotomy) and 4.6 vs. 4.9-5.2 days (thoracotomy) for <70 years vs. >70 years, respectively] and postoperative lung function tests (FEV(1) decrease; 13% <70 years vs. 18% >70 years P=0.34, functional vital capacity decrease; 9% <70 years vs. 14% >70 years P=0.31) are equivalent between the two age groups. Residual QoL following lobectomy (evaluated by patient self-assessment) showed decreased social (P<0.001) and role (P<0.001) functioning but less pain at discharge (P<0.001) in those over 70 years. Global QoL, however, was not influenced by age (global QoL; <70 years 22.2+/-25.3 vs. >70 years 17.6+/-22.9). Pneumonectomy showed statistically significant decreases in physical functioning [six months postoperatively (MPO) P=0.045], role functioning (3 MPO P=0.035), social functioning (6 MPO P=0.006, 12 MPO P=0.001) and general pain (6 MPO P=0.037), but showed no age related differences (<70 years; 81.9+/-19.1, >70 years; 78.0+/-22.8). PMID- 20354038 TI - Evaluation of early and late postoperative flow capacity of internal thoracic artery bypass by means of stress Doppler echocardiography. AB - OBJECTIVES: Arterial revascularization with the internal thoracic artery (ITA) has shown exceptional long-term results, even though early hypoperfusion can occur and can cause ischemia and contractile dysfunction. Therefore, it is still controversial as to whether the bypass vessel can guarantee the required demand for blood flow during the early postoperative (EPO) phase or whether this is only possible a long time after the operation. This question is important particular in the early postoperative phase to manage afterload and reduce left ventricular oxygen demand. Therefore, stress Doppler echocardiography was performed to assess EPO and late postoperative (LPO) flow capacity after minimal-invasive coronary artery bypass grafting (MIDCAB) in subjects with single vessel disease. METHODS: Doppler echocardiography was performed after MIDCAB in 15 patients (mean age 65 years+/-12 standard deviation) in the EPO (15 days) and LPO (266 days) at rest and under stress. RESULTS: The mean diastolic velocity (MDV) as a measure for the coronary perfusion in the bypass-graft was comparable (30.9+/-14.5 EPO to 30.8+/ 13.9 cm/s LPO, P>0.05) for both settings (early vs. late). In both tests, the stress reactions by means of handgrip maneuver lead to comparable increases in blood flow: MDV 65.0+/-54.4% (EPO) to 62.5+/-53.7% n.s. (LPO). The flow increase in the bypass graft was just as similar [48.2+/-46.2% (EPO) to 51.1+/-41.6% n.s. (LPO)]. CONCLUSION: The stress echocardiography revealed for the first time that the ITA-graft after MIDCAB-operation is able to produce the same flow reserve through the EPO phase as well as the LPO phase. Restrictions to a maximum early flow adaptation are not justified. Thus, particularly a patient with severe comorbidities or higher age should be mobilized in the EPO phase to minimize the postoperative complications without risk of myocardial ischemia caused by impaired early blood flow through recent implanted ITA. This method for assessment of ITA blood flow allows for long-time observations and can detect disturbances in perfusion at an early stage. PMID- 20354039 TI - Text messaging as a tool for behavior change in disease prevention and management. AB - Mobile phone text messaging is a potentially powerful tool for behavior change because it is widely available, inexpensive, and instant. This systematic review provides an overview of behavior change interventions for disease management and prevention delivered through text messaging. Evidence on behavior change and clinical outcomes was compiled from randomized or quasi-experimental controlled trials of text message interventions published in peer-reviewed journals by June 2009. Only those interventions using text message as the primary mode of communication were included. Study quality was assessed by using a standardized measure. Seventeen articles representing 12 studies (5 disease prevention and 7 disease management) were included. Intervention length ranged from 3 months to 12 months, none had long-term follow-up, and message frequency varied. Of 9 sufficiently powered studies, 8 found evidence to support text messaging as a tool for behavior change. Effects exist across age, minority status, and nationality. Nine countries are represented in this review, but it is problematic that only one is a developing country, given potential benefits of such a widely accessible, relatively inexpensive tool for health behavior change. Methodological issues and gaps in the literature are highlighted, and recommendations for future studies are provided. PMID- 20354040 TI - Depression and cardiac risk: present status and future directions. PMID- 20354042 TI - Introducing a professional development framework for postgraduate medical supervisors in secondary care: considerations, constraints and challenges. AB - PURPOSE OF STUDY: As the duration of postgraduate training becomes shorter, direct patient contact time is reduced, and supervision becomes more distributed, there is a move to 'professionalise' postgraduate medical education. This paper reports an initiative in one postgraduate training institution (the London Deanery) to develop and introduce a developmental framework and system of portfolio-based review of educational supervisors in the secondary care setting. STUDY DESIGN: 16 acute, mental health, foundation and primary-care Trusts participated in a pilot project, which was subsequently evaluated using focus groups and a semistructured questionnaire. RESULTS: Thematic analysis of transcripts identified a number of considerations, constraints and challenges, important observations given the current policy intention of the UK health departments to introduce mandatory training and performance review for educational supervisors. CONCLUSION: This pilot study shows that such a process can be implemented at local level if facilitated by a clear and unambiguous developmental framework that can be applied flexibly across all specialities. Systems of review also need to be simple and straightforward, take into account existing appraisal processes, and simultaneously address issues of motivation, recognition and reward. PMID- 20354041 TI - Fear of dying in an ethnically diverse society: cross-sectional studies of people aged 65+ in Britain. AB - AIM: To examine fears about dying in an ethnically diverse population sample, and a more homogeneous population sample, aged 65 and over. METHODS: Personal interviews with people aged 65+ living at home responding to two Office for National Statistics Omnibus Surveys in Britain, and two Ethnibus Surveys of ethnically diverse populations in Britain. RESULTS: Ethnically diverse respondents were more likely than British population respondents to express fears about dying on all measures used. Respondents in both samples with better, compared with worse, quality of life had significantly reduced odds of having extreme fears of dying (ethnically diverse sample, OR 0.924 (95% CI 0.898 to 0.951); British population sample, OR 0.981 (95% CI 0.966 to 0.996); both p<0.001). In the latter sample only, older age was protective (OR 0.957; 95% CI 0.930 to 0.985; p<0.001), whereas in the Ethnibus sample, having a longstanding illness (OR 2.024; 95% CI 1.158 to 3.535; p<0.05) and having more relatives to help them (OR 1.134; 95% CI 1.010 to 1.274; p<0.05) increased fears about dying. CONCLUSIONS: Enabling older people to express fears about dying is likely to be important when planning supportive end-of-life care. Practitioners should not assume that fears about dying are the same in different social groups, or that extensive family support is protective against such anxiety. Older people from ethnic minorities had more anxieties about dying than others, and were more likely to express fears the more extensive their family support. These findings have implications for commissioners and practitioners of primary and secondary care. PMID- 20354043 TI - Clinical experience of methotrexate in Crohn's disease: response, safety and monitoring of treatment. AB - BACKGROUND: Methotrexate is an immunosuppressant used in the treatment of patients with Crohn's disease who are intolerant or refractory to azathioprine. AIM: To present clinical experience in terms of response, side effects and reason for cessation of methotrexate treatment as well as adherence to monitoring regimens. DESIGN: Retrospective review of case records of 37 patients taking methotrexate for Crohn's disease at the Bristol Royal Infirmary, a large UK teaching hospital. Thirty-five patients used oral methotrexate. RESULTS: Response rate to methotrexate was 78% at 3 months. Adverse events were uncommon and rarely dangerous. Monitoring of treatment did not adhere to British Society of Gastroenterology guidelines. CONCLUSION: Oral methotrexate is effective and safe in the treatment of Crohn's disease. This is in contrast to findings of previous series, which have mainly reported on intramuscular methotrexate use. Monitoring of treatment is currently inadequate and consensus should be sought for a pragmatic monitoring schedule to resolve this important governance issue. PMID- 20354044 TI - Inadequate control of heart rate in patients with stable angina: results from the European heart survey. AB - AIMS: To examine resting heart rate (HR) in a population presenting with stable angina in relation to prior and subsequent pharmacological treatment, comorbid conditions and clinical outcome. METHODS AND RESULTS: The European Heart Survey was a prospective, observational, cohort study of 3779 patients with stable angina newly presenting to cardiology services. Mean baseline resting HR was 73 beats/min (bpm) and 52.3% of patients had a baseline HR > 70 bpm. Over half of patients were on no chronotropic medication at baseline. Patients with chronic respiratory disease or diabetes had higher resting HRs (75-76 bpm), and were more likely to have been receiving calcium channel blockers at baseline assessment. Overall, beta-blockers were the most common treatment administered following cardiologist assessment, but were used less frequently in patients with chronic respiratory disease and diabetes, and the dosages used were less than that found to be effective in clinical trials. Mean daily doses of metoprolol, bisoprolol, carvedilol, and atenolol were 75 mg, 6 mg, 19 mg and 55 mg, respectively. Higher HR at baseline was associated with higher rates of cardiovascular mortality and hospitalisation for heart failure. CONCLUSION: Control of ischaemic symptoms through heart rate modification in patients with angina is currently inadequate, both by primary referring physicians and cardiologists. Given the adverse outcome associated with higher resting heart rates in this as in other studies, and the availability of specific HR reducing strategies, attention should be given to achieving optimal HR control. PMID- 20354045 TI - Imaging evaluation of demyelinating processes of the central nervous system. AB - Demyelinating processes involving the central nervous system have a variety of aetiologies and can be separated into primary and secondary demyelinating processes. The classic example of primary demyelination is multiple sclerosis. Secondary demyelination, where the aetiology is known, includes infectious, metabolic and toxic disease processes. The underlying component of all demyelinating disorders is damage to the myelin sheath and/or the oligodendrocyte, the cell forming the myelin sheath. These processes often have similar imaging findings, making knowledge of the patient's history, physical examination and laboratory evaluation imperative for developing a differential diagnosis. This pictorial essay provides a review of the imaging of these diverse disorders. PMID- 20354046 TI - Primary, secondary and tertiary effects of eco-climatic change: the medical response. AB - Climatic and ecological change threaten human health globally. Manifestations include lost species, vanishing glaciers and more frequent heavy rain. In the second half of this century, accelerating sea level rise is likely to cause crop loss, and population dislocation. These problems may be magnified by dysfunctional human responses, including conflict. The population health consequences of these events can be classified as primary, secondary and tertiary. Primary signs include the acute and chronic stress of heat waves, and trauma from increased bush fires and flooding. Secondary signs are indirect, such as an altered distribution of arthropod vectors, intermediate hosts and pathogens that will produce changes in the epidemiology of many infectious diseases. More severe future health consequences of climate change are classified here as tertiary effects. If moderate or severe climate change scenarios prove accurate then these manifestations will occur over large areas, and could include famine, war and significant population displacement. Such effects would threaten governance and health. The health professions must respond to these challenges, especially the task of recognising and seeking to minimise tertiary health consequences. The gap between what we know and what we need to know concerning these issues can be narrowed by a new field of medical practice. The framework for this emerging discipline includes climate change, ecology and global health. Combined, these dimensions may be called ecomedicine. Actions to reduce individual emissions, to promote active transport (with its 'co-benefit' of preventing chronic disease), and involvement in group action to protect the environment and to prevent war, informed by understanding of the health of individual patients and populations, will be central to the practice of ecomedicine. PMID- 20354047 TI - Malignant middle cerebral artery (MCA) infarction: pathophysiology, diagnosis and management. AB - 'Malignant MCA infarction' is the term used to describe rapid neurological deterioration due to the effects of space occupying cerebral oedema following middle cerebral artery (MCA) territory stroke. Early neurological decline and symptoms such as headache and vomiting should alert the clinician to this syndrome, supported by radiological evidence of cerebral oedema and mass effect in the context of large hemispheric infarction. The prognosis is generally poor, and death usually occurs as a result of transtentorial herniation and brainstem compression. Treatment options include general measures and pharmacological agents to limit the extent of oedema, and surgical decompression to relieve the pressure effects. Until recently there has been little evidence to guide appropriate treatment, though in the last few years randomised data have been published addressing the role of surgical decompression. A pooled analysis of three European randomised controlled trials suggests that hemicraniectomy performed within 48 h significantly reduces mortality, and improves functional outcome in selected patients, and this has been reflected in recent national guidelines. PMID- 20354048 TI - Recent advances in rheumatoid arthritis. AB - Management of rheumatoid arthritis (RA) has radically changed over the last decade. Diagnostic methods have improved with availability of highly specific tests such as antibody to cyclic citrullinated peptide (specificity approximately 96%), and introduction of advanced imaging modalities such as ultrasound and magnetic resonance imaging to facilitate earlier diagnosis. The current aim of management is to achieve remission and prevent joint damage. In order to achieve this goal, inflammation is suppressed as much as possible during the early phase of the disease before onset of joint damage. Aggressive treatments with combinations of disease modifying anti-rheumatic drugs are commenced earlier in the course of disease, and tight control maintained with regular objective monitoring of disease activity. Early use of anti-TNFalpha (tumour necrosis factor alpha) therapy in combination with methotrexate helps to achieve better clinical and radiographic outcomes, which can be maintained for up to 5 years after withdrawal of anti-TNFalpha therapy. Apart from anti-TNFalpha, several other biological treatments are now available, including those that target CD20 on B cells (rituximab), cytokines such as IL1 (anakinra) and IL6 (tocilizumab), and molecules that cause interaction between antigen presenting cells and T cells (abatacept). There is better awareness and understanding of RA associated complications such as cardiovascular disease and osteoporosis. Use of non steroidal anti-inflammatory drugs is on the decline in light of recent concerns about cardiovascular safety. Evidence is emerging in support of statins and bisphosphonates for improving RA disease activity and preventing erosions, respectively. In the coming years, further improvements in therapeutic strategies are likely with the pace at which research is currently progressing. PMID- 20354049 TI - High cervical intradural lipoma. PMID- 20354050 TI - The seagull sign. PMID- 20354051 TI - Peritoneal hydatidosis. PMID- 20354052 TI - Intratesticular varicocele. PMID- 20354053 TI - Occupational exposure to organic solvents during bridge painting. AB - Exposure to volatile organic compounds (VOCs) from bridge painting was measured in New York City and New Jersey during the summer and fall seasons from 2005 to 2007. The effect of painting activities (paint coating layer, confinement setup, and application method) and meteorological conditions (temperature, humidity, and wind speed) on solvent exposure to aromatic, ketone, ester, and alkane compounds were individually evaluated. Mixed-effect models were used to examine the combination effects of these factors on the air concentration of total VOCs as the individual compound groups were not present in all samples. Air concentration associated with spraying was not affected by meteorological conditions since spraying was done in a confined space, thus reducing their impact on solvent air concentration. The mixed models for brushing and rolling samples included two fixed factors, i.e. application method and temperature, and one random factor, i.e. sampling day. An independent dataset (daily air samples) was used to validate the mixed model constructed for brushing and rolling samples. The regression line of the predicted values and actual measurements had a slope of 1.32 +/- 0.15 for daily brushing and rolling samples, with almost all points being within the 95% confidence bands. The constructed model provides practical approaches for estimating the solvent exposure from brushing and rolling activities among construction painters. An adjusted mean air concentration derived from the activity-specific spray samples was the best estimate for that painting application. PMID- 20354054 TI - Passive airborne dust sampling with the electrostatic dustfall collector: optimization of storage and extraction procedures for endotoxin and glucan measurement. AB - We recently introduced a passive dust sampling method for airborne endotoxin and glucan exposure assessment-the electrostatic dustfall collector (EDC). In this study, we assessed the effects of different storage and extraction procedures on measured endotoxin and glucan levels, using 12 parallel EDC samples from 10 low exposed indoor environments. Additionally, we compared 2- and 4-week sampling with the prospect of reaching higher dust yields. Endotoxin concentrations were highest after extraction with pyrogen-free water (pf water) + Tween. Phosphate buffered saline (PBS)-Tween yielded significantly (44%) lower levels, and practically no endotoxin was detected after extraction in pf water without Tween. Glucan levels were highest after extraction in PBS-Tween at 120 degrees C, whereas extracts made in NaOH at room temperature or 120 degrees C were completely negative. Direct extraction from the EDC cloth or sequential extraction after a preceding endotoxin extraction yielded comparable glucan levels. Sample storage at different temperatures before extraction did not affect endotoxin and glucan concentrations. Doubling the sampling duration yielded similar endotoxin and only 50% higher glucan levels. In conclusion, of the tested variables, the extraction medium was the predominant factor affecting endotoxin and glucan yields. PMID- 20354055 TI - Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. AB - AIMS: To investigate the association of chocolate consumption with measured blood pressure (BP) and the incidence of cardiovascular disease (CVD). METHODS AND RESULTS: Dietary intake, including chocolate, and BP were assessed at baseline (1994-98) in 19 357 participants (aged 35-65 years) free of myocardial infarction (MI) and stroke and not using antihypertensive medication of the Potsdam arm of the European Prospective Investigation into Cancer and Nutrition. Incident cases of MI (n = 166) and stroke (n = 136) were identified after a mean follow-up of approximately 8 years. Mean systolic BP was 1.0 mmHg [95% confidence interval (CI) -1.6 to -0.4 mmHg] and mean diastolic BP 0.9 mmHg (95% CI -1.3 to -0.5 mmHg) lower in the top quartile compared with the bottom quartile of chocolate consumption. The relative risk of the combined outcome of MI and stroke for top vs. bottom quartiles was 0.61 (95% CI 0.44-0.87; P linear trend = 0.014). Baseline BP explained 12% of this lower risk (95% CI 3-36%). The inverse association was stronger for stroke than for MI. CONCLUSION: Chocolate consumption appears to lower CVD risk, in part through reducing BP. The inverse association may be stronger for stroke than for MI. Further research is needed, in particular randomized trials. PMID- 20354056 TI - Does functional change predict the course of improvement in geriatric inpatient rehabilitation? AB - OBJECTIVE: The evaluation of rehabilitation success as measured by different tools is becoming increasingly important in terms of time and money allocation. We wanted to know whether functional change in the first week predicts subsequent improvement in a geriatric inpatient rehabilitation clinic. DESIGN: Observational longitudinal study. SETTING: Geriatric inpatient rehabilitation clinic in Germany. SUBJECTS: One hundred and sixty-one inpatients (117 women) with a median age of 82 years, capable of walking at baseline. MAIN MEASURES: Weekly assessments of physical function were performed from admission until three weeks later. We used a self-rated tool (the function component of the Short Form - Late Life Function and Disability Index), a proxy-rated tool (the Barthel Index) and a performance-based tool (gait speed). We set up linear regression models to estimate the predictive capacity of change in physical function within the first week on change in physical function within the following two weeks. RESULTS: Positive correlations were found between functional change within the first week and total change within three weeks. However, correlations of the same periods of change with subsequent change were negative. Correlations were highly significant for both analysis with P-values <0.0001 when the same measures for prediction and outcome were used. Correlations were inconsistent when prediction and outcome were different. CONCLUSIONS: Improvement within the first week of inpatient rehabilitation is negatively correlated with subsequent functional change. PMID- 20354057 TI - Multidisciplinary rehabilitation after primary total knee arthroplasty: a randomized controlled study of its effects on functional capacity and quality of life. AB - OBJECTIVE: To examine whether a multidisciplinary rehabilitation programme can improve functional recovery and quality of life and reduce the use of rehabilitation services compared with conventional care one year after total knee arthroplasty. DESIGN: Prospective, randomized, non-blinded, controlled trial. SETTING: An outpatient centre-based setting. SUBJECTS: Eighty-six patients who were scheduled for primary total knee arthroplasty due to osteoarthritis of the knee. INTERVENTIONS: A ten-day multidisciplinary rehabilitation programme, which was focused on enhancing functional capacity, was organized 2-4 months after surgery. In both groups, a standard amount of physiotherapy was included in conventional care. MAIN MEASURES: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the 15D, 15-m walk test, stair test, isometric strength measurement of the knee. Use of rehabilitation services was asked about with a questionnaire. Outcomes were assessed preoperatively and at 2-, 6- and 12 month follow-ups. RESULTS: In both groups, functional capacity and quality of life improved significantly. The mean absolute change in the WOMAC function score was -32.4 mm (SD 26.4) in the rehabilitation group and -32.8 mm (SD 20.1) in the control group (P-time*group = 0.40). No difference was found between groups in any outcome measure or in the use of rehabilitation services during the study period. CONCLUSIONS: This study indicates that for knee osteoarthritis patients treated with primary total knee arthroplasty, a 10-day multidisciplinary outpatient rehabilitation programme 2-4 months after surgery does not yield faster attainment of functional recovery or improvement in quality of life than can be achieved with conventional care. PMID- 20354058 TI - Relative contribution of motor impairments to limitations in activity and restrictions in participation in adults with hemiplegic cerebral palsy. AB - OBJECTIVE: To determine which motor impairments make a significant relative contribution to upper limb activity limitations, and whether activity limitations are related to participation restrictions in people with hemiplegic cerebral palsy. DESIGN: An observational study. SETTING: Neurological Rehabilitation Research Group at Faculty of Health Sciences, The University of Sydney. SUBJECTS: Twenty-three people with hemiplegic cerebral palsy participated. MAIN MEASURES: Four motor impairments (strength, coordination, spasticity and contracture), upper limb activity and participation were measured. Multiple regression was used to determine the relative contribution of motor impairments to activity limitations. Linear regression was used to determine the correlation between activity and participation. RESULTS: The four motor impairments accounted for 63% of the variance in upper limb activity with coordination independently accounting for 21% (P<0.01). Upper limb activity accounted for 13% of the variance in participation (P=0.10). CONCLUSIONS: The findings imply that coordination of four motor impairments makes the largest independent relative contribution to activity limitations, whereas upper limb activity makes less contribution to participation in people with mild and moderate hemiplegic cerebral palsy. PMID- 20354059 TI - In vivo antioxidant potentials of Piliostigma thonningii (Schum) leaves: studies on hepatic marker enzyme, antioxidant system, drug detoxifying enzyme and lipid peroxidation. AB - In this study, the in vivo antioxidant potentials of Piliostigma thonningii were investigated in carbon tetrachloride-induced hepatic and oxidative damage in rat. Albino rats were grouped into six, group A rats received sterile distilled water for 14 days while B rats received 0.5 mL/kg body weight of carbon tetrachloride intraperitoneally on day 14. Group C rats received 200 mg/kg body weight of Piliostigma thonningii leaves extract for 14 days. Groups D, E and F rats were pretreated with 50, 100 and 200 mg/kg body weight of Piliostigma thonningii leaves for 14 days and challenged with 0.5 mL/kg body weight of carbon tetrachloride on day 14. The extract treatment significantly attenuated both the decrease and the increase in liver and serum marker enzyme. Antioxidant enzyme activity as well as level of uridyl diphosphoglucuronosyl transferase, quinone oxidoreductase and glutathione S-transferase was significantly induced. There was attenuation of malonidialdehyde and lipid hydroperoxide increase. On the basis of the available data in this report, it can be postulated that Piliostigma thonningii leaves protect liver against hepatic and oxidative damage by carbon tetrachloride possibly by acting as an in vivo free radical scavenger, induction of antioxidant enzymes, drug detoxifying enzymes and prevention of excessive stimulation of antioxidant enzyme and lipid peroxidation. PMID- 20354060 TI - Reliability of history of acetaminophen ingestion in intentional drug overdose patients. AB - The objective of this study was to determine the reliability of denial of acetaminophen ingestion in intentional drug overdose patients. All intentional drug overdose patients admitted to an emergency department who were able to provide a history were included. A detailed history was obtained on names, timing and number of medications ingested, and serum acetaminophen was assayed. Multidrug ingestion was defined as the reporting of >=2 medications. Patients were considered 'reliable' if they reported acetaminophen ingestion and had detectable acetaminophen levels or the other way around. Validity parameters of acetaminophen history were assessed by sensitivity, specificity and positive and negative predictive values. A total of 154 patients were included. History was significantly more reliable in patients who denied ingestion of acetaminophen (n = 107) compared with patients who reported it (n = 47; 95.3% vs 65.9%, respectively; p < 0.0001, 95% CI of the difference 17.5%-41.2%). No suicidal patient who denied both acetaminophen and multidrug ingestions had a detectable acetaminophen level (negative predictive value 1, 95% CI 0.93-1.0). It is suggested that denial of both acetaminophen and multidrug ingestions by intentional drug overdose patients after a thorough history taking can be considered reliable for acetaminophen history. In facilities with limited resources, these patients may not require routine acetaminophen screening. PMID- 20354061 TI - Intoxication by large amounts of barium nitrate overcome by early massive K supplementation and oral administration of magnesium sulphate. AB - Suicide by ingestion of barium is exceptionally rare. Adverse health effects depend on the solubility of the barium compound. Severe hypokalemia, which generally occurs within 2 hours after ingestion, is the predominating feature of acute barium toxicity, subsequently leading to adverse effects on muscular activity and cardiac automaticity. We report one case of acute poisoning with barium nitrate, a soluble barium compound. A 75-year-old woman was hospitalized after suicidal ingestion of a burrow mole fumigant containing 12.375 g of barium nitrate. About 1 hour post-ingestion, she was only complaining of abdominal pain. The ECG recording demonstrated polymorphic ventricular premature complexes (VPCs). Laboratory data revealed profound hypokalemia (2.1 mmol/L). She made a complete and uneventful recovery after early and massive potassium supplementation combined with oral magnesium sulphate to prevent barium nitrate absorption. PMID- 20354062 TI - Hematological and biochemical profiles and histopathological evaluation of experimental intoxication by sodium fluoroacetate in cats. AB - Sodium fluoroacetate (SFAC) is a potent rodenticide, largely used for rodent and domestic pest control. The toxic effects of SFAC are caused by fluoroacetate, a toxic metabolite, whose toxic action blocks the Krebs cycle and also induces the accumulation of citrate in the body, which is a serum calcium chelator. The most common clinical signs of this intoxication are the cardiac and neurological effects. However, the hematological, biochemical and histopathological findings occurring in intoxication are still unknown in different species. In the present study, 16 domestic cats were experimentally intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The hematological and biochemical profiles and histopathological findings were made to look for auxiliary diagnosis methods in SFAC intoxications. The hematological profile showed transitory leucopenia and thrombocytopenia; in the biochemical profiles were detected hyperglycemia, increase of creatinequinase enzyme (CK) and creatinequinase cardiac isoenzyme (CK MB), hypokalemia and hypophosfatemia. In the macroscopic and histopathological findings were observed lesions characteristic of degenerative and ischemic processes in heart, kidneys, liver, brain and lungs. These changes may be auxiliary to the diagnosis of intoxication by SFAC in cats, when associated with clinical signs described for the species. Thus, the complete blood count with platelet count, serum glucose, enzymes CK and CK-MB isoenzyme, as well as the electrolytes potassium and phosphorus, can facilitate the laboratory diagnosis during intoxication by SFAC, associated with the pathological findings in the case of death of the intoxicated animal. PMID- 20354063 TI - Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of coronary heart disease. AB - To clarify the role of glutathione S-transferases (GSTs; GSTM1 and GSTT1) status in susceptibility to coronary heart disease (CHD), a meta-analysis of published studies was performed. A total of 19 studies including 8020 cases and 11 501 controls were included in this meta-analysis. In a combined analysis, the relative risks for CHD of the GSTM1 null and GSTT1 null polymorphisms were 1.47 [95% confidence interval (CI): 1.08-2.01] and 1.26 (95% CI: 0.90-1.75), respectively. Three potential sources of heterogeneity including ethnicity, source of control and sample size of study were also assessed. However, no significant association was found in stratified analyses. By pooling data from eight studies (2909 cases and 3745 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for CHD [odds ratio (OR = 2.38, 95% CI: 1.03-5.48)] was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. Results from the meta-analysis of five studies on GSTs stratified according to smoking status showed an increased risk for individuals with null genotype (OR = 2.21, 95% CI: 1.24-3.92 for GSTM1 and OR = 3.29, 95% CI: 1.49-7.26 for GSTT1) versus non-null genotypes. This meta-analysis suggests that the GSTM1 null genotype may slightly increase the risk of CHD and that interaction between unfavourable GSTs genotypes may exist. PMID- 20354065 TI - Five-year survival in a Program of All-inclusive Care for Elderly compared with alternative institutional and home- and community-based care. AB - BACKGROUND: Community-based services are preferred to institutional care for people requiring long-term care (LTC). States are increasing their Medicaid waiver programs, although Program of All-Inclusive Care For Elderly (PACE) prepaid, community-based comprehensive care-is available in 31 states. Despite emerging alternatives, little is known about their comparative effectiveness. METHODS: For a two-county region of South Carolina, we contrast long-term survival among entrants (n = 2040) to an aged and disabled waiver program, PACE, and nursing homes (NHs), stratifying for risk. Participants were followed for 5 years or until death; those lost to follow-up or surviving less than 5 years as on August 8, 2005 were censored. Analyses included admission descriptive statistics and Kaplan-Meier curves. To address cohort risk imbalance, we employed an established mortality risk index, which showed external validity in waiver, PACE, and NH cohorts (log-rank tests = 105.42, 28.72, and 52.23, respectively, all p < .001; c-statistics = .67, .58, .65, p < .001). RESULTS: Compared with waiver (n = 1,018) and NH (n = 468) admissions, PACE participants (n = 554) were older, more cognitively impaired, and had intermediate activities of daily living dependency. PACE mortality risk (72.6% high-to-intermediate) was greater than in waiver (58.8%), and similar to NH (71.6%). Median NH survival was 2.3 years. Median PACE survival was 4.2 years versus 3.5 in waiver (unstratified, log rank = .394; p = .53), but accounting for risk, PACE's advantage is significant (log rank = 5.941 (1); p = .015). Compared with waiver, higher risk admissions to PACE were most likely to benefit (moderate: PACE median survival = 4.7 years vs waiver 3.4; high risk: 3.0 vs 2.0). CONCLUSION: Long-term outcomes of LTC alternatives warrant greater research and policy attention. PMID- 20354064 TI - Applications of cold temperature stress to age fractionate Caenorhabditis elegans: a simple inexpensive technique. AB - The nematode Caenorhabditis elegans's (CE) successful use in studies of aging is well documented. Cold temperature stress of mixed populations of CE provides a rapid inexpensive means of obtaining three life stage-specific cohorts. Cohorts are obtained in quantities that allow acquisition of replicate metabolite profiles of changes associated with development, aging, and senescence. The fractionation technique is effective with monoxenic and axenic CE cultures. Cohort Y contains 100% young worms, and Cohort A contains 75% adult worms. Cohort M, prereproductive and reproductive, contains some A and Y due to continuous egg laying and hatch. Principal component analysis of normalized data from metabolite profiles obtained using high-performance liquid chromatography electrochemical analysis clearly separates Cohort Y from Cohort A and monoxenic from axenic cultured worms. Access to replicate quantities of age-defined worms will aid studies of alterations in homeostatic controls associated with aging and senescence. PMID- 20354066 TI - Interleukin 18 receptor 1 expression distinguishes patients with multiple sclerosis. AB - Definition of dysregulated immune components in multiple sclerosis may help in the identification of new therapeutic targets. Deviation of the interleukin 18 receptor 1 (IL18R1) is of particular interest since the receptor is critical for experimental neuroinflammation. The objective of this study was to determine whether expression of IL18R1 varies between multiple sclerosis patients and controls, and to test genetic association of IL18R1 with multiple sclerosis. We used quantitative real-time PCR to assess mRNA levels of IL18R1 in cerebrospinal fluid and peripheral blood mononuclear cells of 191 patients with multiple sclerosis, 61 patients with clinically isolated syndrome and 168 controls having other neurological disorders. Association was tested in 2153 patients with multiple sclerosis and 1733 controls using 13 tagging single nucleotide polymorphisms within the IL18R1 gene. We found that patients with multiple sclerosis had increased IL18R1 mRNA expression in both cerebrospinal fluid cells (p < 0.05) and peripheral blood mononuclear cells (p < 0.05) compared with controls. Patients with clinically isolated syndrome had elevated levels compared with controls in cerebrospinal fluid cells (p < 0.001) but not in peripheral blood mononuclear cells. The gene was not associated to multiple sclerosis. We conclude that the increased expression of IL18R1 may contribute pathogenically to disease and is therefore a potential therapeutic target. The absence of a genetic association in the IL18R1 gene itself suggests regulation from other parts of the genome, or as part of the inflammatory cascade in multiple sclerosis without a prime genetic cause. PMID- 20354068 TI - Correlates of self-stigma among outpatients with mental illness in Lagos, Nigeria. AB - BACKGROUND: Studies in this region have all been limited to public stigma whereas little is known about the extent of self-stigma. AIMS: To assess the extent, domains and correlates of self-stigma among psychiatric outpatients in Lagos, Nigeria. METHOD: Psychiatric outpatients (n = 342) from three centres completed a modified version of the Internalized Stigma of Mental Illness scale (ISMI) as a measure of their self-stigma. They were also evaluated for various sociodemographic and clinical related variables. RESULTS: A total of 74 (n = 21.6%) patients were classified as having 'high self-stigma'. The correlates of high self-stigma included unemployment (OR 3.85, 95% CI 2.55-7.00), poor social support (OR 10.82, 95% CI 4.85-24.84), longer duration of illness (OR 10.35, 95% CI 4.36-25.78) and having full insight into the illness (OR 4.23, 95% CI 2.16 8.76). CONCLUSIONS: Self-stigma is a common phenomenon in psychiatric outpatients in this environment. The present anti-stigma programmes must extend to regions of sub-Saharan Africa and incorporate self-stigma as a matter of priority. PMID- 20354067 TI - Depressive symptoms and their social contexts: a qualitative systematic literature review of contextual interventions. AB - BACKGROUND: Numerous observational studies demonstrate associations between social context and depressive symptoms, yet few intervention trials exist in this arena. AIMS: This review examines intervention trials that explore the impact of contextual change on depressive symptoms. METHODS: Electronic literature databases of PubMed and PsycINFO, bibliographies of retrieved articles and the publicly available internet were searched for English-language articles published between 1997 and 2008. Peer-reviewed studies were eligible for inclusion if they reported contextual interventions and depressive symptoms measures in adult populations without other significant underlying medical or psychological illness. In total, 2,128 studies met search term criteria. Of these, 13 studies meeting inclusion criteria were classified by type of intervention. Qualitative synthesis was used to interpret the mental health impact of contextual interventions. RESULTS: The interventions focused on employment, housing, poverty, parenting and violence. Eight of these studies reported a decrease in depressive symptoms and/or psychological distress in intervention groups. Interventions varied in focus, length of follow-up and measures of depressive symptoms. CONCLUSIONS: Contextual interventions for the prevention and treatment of depressive symptoms and psychological distress can be effective, though very limited data exist in this field. Policy implications include a greater emphasis on improving context to decrease depression and other mental disorders. PMID- 20354069 TI - A simple circuit for cerebral perfusion during cardiopulmonary bypass surgery of the ascending aorta and the aortic arch. AB - INTRODUCTION: A circuit was developed to allow for rapid reaction to the needs of perfusion during extracorporeal circulation (ECC) in surgery of the aortic arch and ascending aorta. METHOD: From January 2008 through January 2010, a home designed circuit was used on 30 patients with aortic dissection who underwent surgery to replace the ascending aorta and the aortic arch and, in some cases, the aortic valve and re-implant of the coronary arteries using Bentall's technique. PMID- 20354070 TI - Dormancy as exaptation to protect mimetic seeds against deterioration before dispersal. AB - BACKGROUND AND AIMS: Mimetic seeds simulate the appearance of fleshy fruits and arilled seeds without producing nutritive tissues as a reward for seed dispersers. In this strategy of seed dispersal, seeds may remain attached to the mother plant for long periods after maturity, increasing their availability to naive seed dispersers. The hypothesis that seed coat impermeability in many tropical Fabaceae with mimetic seeds serves as an exaptation to protect the seeds from deterioration and rotting while awaiting dispersal was investigated. METHODS: Seed coat impermeability was evaluated in five mimetic-seeded species of tropical Fabaceae in south-eastern Brazil (Abarema langsdorffii, Abrus precatorius, Adenanthera pavonina, Erythrina velutina and Ormosia arborea) and in Erythrina speciosa, a 'basal' species in its genus, which has monochromatic brown seeds and no mimetic displays. Seed hardness was evaluated as a defence against accelerated ageing (humid chamber at 41 degrees C for 144 h). Seed development and physiological potential of O. arborea was evaluated and the effect of holding mature seeds in pods on the mother plant in the field for a period of 1 year under humid tropical conditions was compared with seeds stored under controlled conditions (15 degrees C and 40 % relative air humidity). KEY RESULTS: All five mimetic-seeded species, and E. speciosa, showed strong coat impermeability, which protected the seeds against deterioration in accelerated ageing. Most O. arborea seeds only became dormant 2 months after pod dehiscence. Germination of seeds after 1 year on the plant in a humid tropical climate was 56 %, compared with 80 % for seeds stored in controlled conditions (15 degrees C, 45 % relative humidity). Seedling shoot length after 1 year did not differ between seed sources. CONCLUSIONS: Dormancy acts in mimetic-seeded species as an exaptation to reduce seed deterioration, allowing an increase in their effective dispersal period and mitigating the losses incurred by low removal rates by naive avian frugivores. PMID- 20354071 TI - Ecophysiological response of Crambe maritima to airborne and soil-borne salinity. AB - BACKGROUND AND AIMS: There is a need to evaluate the salt tolerance of plant species that can be cultivated as crops under saline conditions. Crambe maritima is a coastal plant, usually occurring on the driftline, with potential use as a vegetable crop. The aim of this experiment was to determine the growth response of Crambe maritima to various levels of airborne and soil-borne salinity and the ecophysiological mechanisms underlying these responses. METHODS: In the greenhouse, plants were exposed to salt spray (400 mM NaCl) as well as to various levels of root-zone salinity (RZS) of 0, 50, 100, 200 and 300 mM NaCl during 40 d. The salt tolerance of Crambe maritima was assessed by the relative growth rate (RGR) and its components. To study possible salinity effects on the tissue and cellular level, the leaf succulence, tissue Na(+) concentrations, Na(+) : K(+) ratio, net K(+)/Na(+) selectivity, N, P, K(+), Ca(2+), Mg(2+), proline, soluble sugar concentrations, osmotic potential, total phenolics and antioxidant capacity were measured. KEY RESULTS: Salt spray did not affect the RGR of Crambe maritima. However, leaf thickness and leaf succulence increased with salt spray. Root zone salinities up to 100 mM NaCl did not affect growth. However, at 200 mM NaCl RZS the RGR was reduced by 41 % compared with the control and by 56 % at 300 mM NaCl RZS. The reduced RGR with increasing RZS was largely due to the reduced specific leaf area, which was caused by increased leaf succulence as well as by increased leaf dry matter content. No changes in unit leaf rate were observed but increased RZS resulted in increased Na(+) and proline concentrations, reduced K(+), Ca(2+) and Mg(2+) concentrations, lower osmotic potential and increased antioxidant capacity. Proline concentrations of the leaves correlated strongly (r = 0.95) with RZS concentrations and not with plant growth. CONCLUSIONS: Based on its growth response, Crambe maritima can be classified as a salt spray tolerant plant that is sensitive to root zone salinities exceeding 100 mM NaCl. PMID- 20354072 TI - Climate change and invasion by intracontinental range-expanding exotic plants: the role of biotic interactions. AB - BACKGROUND AND AIMS: In this Botanical Briefing we describe how the interactions between plants and their biotic environment can change during range-expansion within a continent and how this may influence plant invasiveness. SCOPE: We address how mechanisms explaining intercontinental plant invasions by exotics (such as release from enemies) may also apply to climate-warming-induced range expanding exotics within the same continent. We focus on above-ground and below ground interactions of plants, enemies and symbionts, on plant defences, and on nutrient cycling. CONCLUSIONS: Range-expansion by plants may result in above ground and below-ground enemy release. This enemy release can be due to the higher dispersal capacity of plants than of natural enemies. Moreover, lower latitudinal plants can have higher defence levels than plants from temperate regions, making them better defended against herbivory. In a world that contains fewer enemies, exotic plants will experience less selection pressure to maintain high levels of defensive secondary metabolites. Range-expanders potentially affect ecosystem processes, such as nutrient cycling. These features are quite comparable with what is known of intercontinental invasive exotic plants. However, intracontinental range-expanding plants will have ongoing gene-flow between the newly established populations and the populations in the native range. This is a major difference from intercontinental invasive exotic plants, which become more severely disconnected from their source populations. PMID- 20354073 TI - The role of plant traits and their plasticity in the response of pasture grasses to nutrients and cutting frequency. AB - BACKGROUND AND AIMS: Although plant functional traits (PFTs) appear to be important indicators of species' responses to land use changes, there is no clear understanding of how the variations in traits and their plasticity determine variations in species performance. This study investigated the role of functional shoot traits and their plasticity for variation in above-ground net primary productivity (ANPP) due to changes in N supply and in cutting frequency for 13 native perennial C(3) grass species. METHODS: Monocultures of the grass species were grown in a fully factorial block design combining plant species, cutting frequency and N supply as factors. KEY RESULTS: Four major trait associations were obtained by reducing the dimensions of 14 PFTs with a principal component analysis (PCA).Variations in species' productivity in response to an increase in cutting frequency was mainly explained by traits linked to the first PCA axis, opposing high plant stature from lower shoot cellulose and lignin contents and high leaf N content. Variation in species productivity in response to change in N supply was mainly explained by a set of predictor variables combining traits (average flowering date) and a trait's plasticity (tiller density per unit land area and leaf dry matter content, i.e. mg dry matter g fresh mass(-1)). These traits involved are linked to the second PCA axis ('nutrient acquisition conservation'), which opposes distinct strategies based on response to nutrient supply. CONCLUSIONS: Variations in ANPP of species in response to an increase in cutting frequency and a decrease in N supply are controlled by a group of traits, rather than by one individual trait. Incorporating plasticity of the individual traits into these trait combinations was the key to explaining species' productivity responses, accounting for up to 89 % of the total variability in response to the changes in N supply. PMID- 20354074 TI - Physical activity and change in mammographic density: the Study of Women's Health Across the Nation. AB - One potential mechanism by which physical activity may protect against breast cancer is by decreasing mammographic density. Percent mammographic density, the proportion of dense breast tissue area to total breast area, declines with age and is a strong risk factor for breast cancer. The authors hypothesized that women who were more physically active would have a greater decline in percent mammographic density with age, compared with less physically active women. The authors tested this hypothesis using longitudinal data (1996-2004) from 722 participants in the Study of Women's Health Across the Nation (SWAN), a multiethnic cohort of women who were pre- and early perimenopausal at baseline, with multivariable, repeated-measures linear regression analyses. During an average of 5.6 years, the mean annual decline in percent mammographic density was 1.1% (standard deviation = 0.1). A 1-unit increase in total physical activity score was associated with a weaker annual decline in percent mammographic density by 0.09% (standard error = 0.03; P = 0.01). Physical activity was inversely associated with the change in nondense breast area (P < 0.01) and not associated with the change in dense breast area (P = 0.17). Study results do not support the hypothesis that physical activity reduces breast cancer through a mechanism that includes reduced mammographic density. PMID- 20354075 TI - Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice. AB - G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5/M-Bar/GPR131) is a cell surface receptor involved in the regulation of bile acid metabolism. We have previously shown that Gpbar1-null mice are resistant to cholesterol gallstone disease when fed a lithogenic diet. Other published studies have suggested that Gpbar1 is involved in both energy homeostasis and glucose homeostasis. Here, we examine the functional role of Gpbar1 in diet-induced obese mice. We found that body weight, food intake, and fasted blood glucose levels were similar between Gpbar1-null mice and their wild-type (WT) littermates when fed a chow or high-fat diet (HFD) for 2 months. However, insulin tolerance tests revealed improved insulin sensitivity in male Gpbar1(-/-) mice fed chow, but impaired insulin sensitivity when fed a HFD. In contrast, female Gpbar1(-/-) mice exhibited improved insulin sensitivity when fed a HFD compared with their WT littermates. Female Gpbar1(-/-) mice had significantly lower plasma cholesterol and triglyceride levels than their WT littermates on both diets. Male Gpbar1(-/-) mice on HFD displayed increased hepatic steatosis when compared with Gpbar1(+)(/)(+) males and Gpbar1(-/-) females on HFD. These results suggest a gender-dependent regulation of Gpbar1 function in metabolic disease. PMID- 20354076 TI - Inhibiting the ubiquitin-proteasome system leads to preferential accumulation of toxic N-terminal mutant huntingtin fragments. AB - An expanded polyglutamine (polyQ) domain in the N-terminal region of huntingtin (htt) causes misfolding and accumulation of htt in neuronal cells and the subsequent neurodegeneration of Huntington's disease (HD). Clearing the misfolded htt is critical for preventing neuropathology, and this process is mediated primarily by both the ubiquitin-proteasome system (UPS) and autophagy. Although overexpression of mutant htt can inhibit UPS activity in cultured cells, mutant htt does not inhibit global UPS activity in the brains of HD transgenic mice. These findings underscore the importance of investigating the function of the UPS and autophagy in the brain when mutant proteins are not overexpressed. When cultured PC12 cells were treated with either UPS or autophagy inhibitors, more N terminal mutant htt fragments accumulated via inhibition of the UPS. Furthermore, in HD CAG repeat knock-in mouse brain, inhibiting the UPS also resulted in a greater accumulation of N-terminal, but not full-length, mutant htt than inhibiting autophagy did. Our findings suggest that impairment of the UPS may be more important for the accumulation of N-terminal mutant htt and might therefore make an attractive therapeutic target. PMID- 20354077 TI - ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta. AB - The first definitive cell fate decision in development occurs at the blastocyst stage with establishment of the trophoblast and embryonic cell lineages. In the mouse, lineage commitment is achieved by epigenetic regulation of a critical gatekeeper gene, the transcription factor Elf5, that reinforces placental cell fate and is necessary for trophoblast stem (TS) cell self-renewal. In humans, however, the epigenetic lineage boundary seems to be less stringent since human embryonic stem (ES) cells, unlike their murine counterparts, harbour some potential to differentiate into trophoblast derivatives. Here, we show that ELF5 is expressed in the human placenta in villous cytotrophoblast cells but not in post-mitotic syncytiotrophoblast and invasive extravillous cytotrophoblast cells. ELF5 establishes a circuit of mutually interacting transcription factors with CDX2 and EOMES, and the highly proliferative ELF5(+)/CDX2(+) double-positive subset of cytotrophoblast cells demarcates a putative TS cell compartment in the early human placenta. In contrast to placental trophoblast, however, ELF5 is hypermethylated and largely repressed in human ES cells and derived trophoblast cell lines, as well as in induced pluripotent stem cells and murine epiblast stem cells. Thus, these cells exhibit an embryonic lineage-specific epigenetic signature and do not undergo an epigenetic reprogramming to reflect the trophoblast lineage at key loci such as ELF5. Our identification of the trophoblast-specific transcriptional circuit established by ELF5 will be instrumental to derive human TS cell lines that truly reflect early placental trophoblast and that will be most beneficial to gain insights into the aetiology of common pregnancy complications, including intra-uterine growth restriction and pre-eclampsia. PMID- 20354078 TI - The expectations of patients. PMID- 20354079 TI - TB alert. PMID- 20354080 TI - Impacted canines. PMID- 20354081 TI - Trusting research. PMID- 20354082 TI - TM article questioned. PMID- 20354083 TI - Temporomandibular pain. PMID- 20354084 TI - More about tm article. PMID- 20354087 TI - Is sweetness preference based in biology? PMID- 20354088 TI - Trends in dental treatment, 1992 to 2007. AB - BACKGROUND: Reductions in U.S. dental caries levels have been noted since the 1970s. Reports indicate that dental treatment is changing accordingly. The author examined dental insurance claims to determine whether these changes in dental treatment trends of insured people have continued. METHODS: To measure the annual per capita use of dental services, the author used Delta Dental of Michigan, Ohio, and Indiana insurance claims for care provided by dentists in Michigan. The number of patients' claims assessed ranged from 1.25 million in 1992 to 1.84 million in 2007. Within each of these years, the number of each type of service provided was divided by the number of patients receiving treatment of any type, according to birth year. RESULTS: The author found that overall, the per capita number of restorative procedures continued to decline. Resin-based composite restorations continued to be placed instead of amalgam restorations. The number of extractions (except for third-molar extractions) and endodontic procedures continued to decrease slightly. As a result, prosthodontic procedures decreased overall. The use of implants continued to increase. CONCLUSIONS: The patterns in the use of dental services by age of patients continue to change. These changes follow closely the reported changes in the oral health in the population. PRACTICE IMPLICATIONS: The number of restorative and prosthodontic services per person required by patients born more recently is not as great as in patients born earlier. Practitioners might need to adjust the number of patients they treat and the services they provide in the coming decades. PMID- 20354089 TI - The risk of enamel fluorosis and caries among Norwegian children: implications for Norway and the United States. AB - BACKGROUND: The authors investigated the associations between enamel fluorosis, caries and early fluoride use among Norwegian children who received fluoride supplementation under a protocol similar to the current U.S. protocol. METHODS: Two examiners whose techniques were calibrated examined randomly selected middle school-aged children living in Bergen, Norway-where the water supply contains less than 0.10 milligrams of fluoride per liter-for both enamel fluorosis and caries by using the Fluorosis Risk Index and modified National Institute of Dental and Craniofacial Research criteria. The authors ascertained past fluoride exposure via a follow-up questionnaire mailed to parents. RESULTS: The questionnaire had an 88 percent response rate and 87 percent reliability. Adjusted analyses revealed a strong association between regular supplementation (given in the form of lozenges) and mild to moderate enamel fluorosis (odds ratio [OR], 6.85; P < .05), as well as fluorosis of lesser severity (OR, 3.07; P < .05). No children who had exclusively used only a pea-sized amount of toothpaste (0.1 percent fluoride) had mild to moderate fluorosis. The authors found a 40 percent reduction in caries risk associated with early use of pea-sized amounts of fluoridated toothpaste and a 46 percent reduction associated with regular use of fluoride supplement lozenges. CONCLUSIONS: These findings suggest that both risk of fluorosis development and caries-preventive benefit are associated with regular use of fluoride supplements, and caries prevention was associated with early use of a pea-sized amount of toothpaste. CLINICAL IMPLICATIONS: These findings underscore the need for clinicians to consider thoroughly-and discuss with a child's parent or guardian-both the benefit and the potential risk of fluorosis development associated with preventive fluoride agents before introducing them. Clinicians also should emphasize the proper use of such agents. PMID- 20354091 TI - Coming to America: betel nut and oral submucous fibrosis. AB - BACKGROUND: Oral submucous fibrosis (OSF) is an insidious precancerous disease affecting the oral cavity, pharynx and upper digestive tract. Its etiology is linked directly to betel nut use, which is common to the Indian subcontinent. With the increase in immigration of people from the Indian subcontinent to the United States, many American dental professionals will encounter this disease in the near future. The author provides a general overview of OSF. METHODS: The author provides a literature review of OSF, including its epidemiology, etiology, clinical presentation, histopathology and treatment modalities. RESULTS: OSF is a precancerous oral disease linked definitively to the use of betel nut. It is endemic to people in the Indian subcontinent. Patients' primary complaint is progressive trismus. Treatment is based on disease severity. CLINICAL IMPLICATIONS: OSF is a debilitating but preventable oral disease. Its incidence in the United States will increase as the South Asian immigrant population expands. Consequently, American dental professionals may encounter patients with this disease, and it is important that they are aware of it. In addition, for dental care professionals practicing in a South Asian American community, public health education is important to inform the population about the deleterious oral health effects of betel nut consumption. PMID- 20354090 TI - The effectiveness of a preprocedural mouthrinse containing cetylpyridinium chloride in reducing bacteria in the dental office. AB - BACKGROUND: During oral procedures, microorganisms from the oral cavity may contaminate nearby surfaces. The authors evaluated the efficacy of a commercial preprocedural mouthrinse containing 0.05 percent cetylpyridinium chloride (CPC) in reducing the levels and composition of viable bacteria in oral spatter. METHODS: The authors randomly assigned 60 participants receiving oral prophylaxis with an ultrasonic scaler to one of four groups: a preprocedural rinse solution containing 0.05 percent CPC, 0.12 percent chlorhexidine (CHX) or water, or no rinsing. Airborne microorganisms were collected on blood agar plates. The composition of the spatter was analyzed for 39 oral bacterial species by means of checkerboard DNA-DNA hybridization. RESULTS: CPC and CHX were equally effective in lowering the levels of spatter bacteria and performed better than water and no rinsing (P < .05, Kruskal-Wallis test). The composition of the spatter from the control groups showed higher proportions (P < .05, Kruskal-Wallis test) of Fusobacterium species and lower proportions of Capnocytophaga species when compared with the spatter from the CPC and CHX groups. CONCLUSION: A commercial mouthrinse containing 0.05 percent CPC when used as a preprocedural mouthrinse was equally effective as CHX in reducing the levels of spatter bacteria generated during ultrasonic scaling. CLINICAL IMPLICATIONS: Owing to its strong antibacterial effect and the fact that it has fewer side effects than CHX, a solution containing 0.05 percent CPC may be a good alternative to that containing 0.12 CHX as a preprocedural mouthrinse used to help decrease the level of contamination in spatter. PMID- 20354092 TI - Palatal lesions in an otherwise healthy patient. PMID- 20354093 TI - Defining oral neglect in institutionalized elderly: a consensus definition for the protection of vulnerable elderly people. AB - BACKGROUND: The authors administered surveys to develop an operational definition of oral neglect in institutionalized elderly (ONiIE) in the United States. METHODS: The authors administered a Delphi technique survey involving three rounds to a panel of 19 geriatric dental experts in 1995 to arrive at a definition of ONiIE. The authors validated the 1995 ONiIE definition by administering a Delphi technique survey involving four rounds to a subset of eight experts from the 1995 panel. RESULTS: The panelists in the 2009 survey validated the 28 oral diseases or conditions that were part of the 1995 ONiIE definition and added one new oral condition-bleeding. They also reached consensus agreement for each of the 29 listed oral diseases and conditions regarding both the diagnostic stage at which those diseases and conditions should be included in a definition (mild, moderate, or severe) and the specified time period required to constitute neglect (that is, total "time to qualify as neglect" was eight days for acute conditions and 35 days for chronic conditions). CONCLUSIONS: An expert driven consensus ONiIE definition was established. It consists of 29 oral diseases and conditions, each of which has been associated with a diagnostic stage and a specified time period required to constitute neglect. CLINICAL IMPLICATIONS: Since federal legislation that funds payments to nursing homes for the care and housing of their residents requires that there shall be no oral neglect, this validated consensus ONiIE definition provides a utilitarian means to enforce that legislative expectation. PMID- 20354094 TI - Reasons for placement of restorations on previously unrestored tooth surfaces by dentists in The Dental Practice-Based Research Network. AB - OBJECTIVE: The authors conducted a study to identify and quantify the reasons used by dentists in The Dental Practice-Based Research Network (DPBRN) for placing restorations on unrestored permanent tooth surfaces and the dental materials they used in doing so. METHODS: A total of 229 DPBRN practitioner investigators provided data from their practices regarding 9,890 consecutive restorations in 5,810 patients. Information the practitioner-investigators provided included their reasons for restoring the teeth, the specific teeth and surfaces they restored and the restorative materials they used. RESULTS: Primary caries (85 percent of teeth, 8,351 of 9,890) and noncarious defects (15 percent, 1,479 of 9,890) were the main reasons participants gave for placing restorations. Participants placed restorations necessitated by caries most frequently on occlusal surfaces (49 percent, 4,091 of 8,351). They used amalgam for 47 percent of the molar restorations and 45 percent of the premolar restorations. They used directly placed resin-based composite (RBC) for 48 percent of the molar restorations, 50 percent of the premolar restorations and 93 percent of the anterior restorations. CONCLUSION: DPBRN practitioner-investigators cited dental caries on occlusal and proximal surfaces of molar teeth as the main reasons for placing restorations on previously unrestored tooth surfaces. RBC was the material they used most commonly for occlusal and anterior restorations. Amalgam remains the material of choice to restore posterior teeth with proximal caries, although the authors noted significant differences in the use of amalgam and RBC by dentists in various regions of the DPBRN. PMID- 20354095 TI - An in vivo study of the effect of a 38 percent hydrogen peroxide in-office whitening agent on enamel. AB - BACKGROUND: In an in vivo study, the authors tested the hypothesis that no difference in enamel surface roughness is detectable either during or after bleaching with a high-concentration in-office whitening agent. METHODS: The authors performed profilometric and scanning electron microscopic (SEM) analyses of epoxy resin replicas of the upper right incisors of 20 participants at baseline (control) and after each bleaching treatment with a 38 percent hydrogen peroxide whitening agent, applied four times, at one-week intervals. The authors used analysis of variance for repeated measures to analyze the data statistically. RESULTS: The profilometric analysis of the enamel surface replicas after the in vivo bleaching protocol showed no significant difference in surface roughness parameters (P > .05) compared with those at baseline, irrespective of the time interval. Results of the correlated SEM analysis showed no relevant alteration on the enamel surface. CONCLUSIONS: Results of this in vivo study support the tested hypothesis that the application of a 38 percent hydrogen peroxide in-office whitening agent does not alter enamel surface roughness, even after multiple applications. CLINICAL IMPLICATIONS: The use of a 38 percent hydrogen peroxide in-office whitening agent induced no roughness alterations of the enamel surface, even after prolonged and repeated applications. PMID- 20354096 TI - Good evidence supports acetaminophen as an effective and safe reliever of acute postoperative pain. PMID- 20354097 TI - Making Class II resin-based composite restorations predictable and profitable. PMID- 20354098 TI - Purchasing new technologies. PMID- 20354099 TI - How do I ethically handle a request for confidentiality by an elderly patient? PMID- 20354100 TI - Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis. AB - BACKGROUND: Recently, dopamine agonists were proposed as a prophylactic treatment for ovarian hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles. METHODS: We conducted a systematic review and meta-analysis of randomized trials comparing the prophylactic effect of the dopamine agonist, cabergoline, versus no treatment in IVF/ICSI cycles. Primary outcome was OHSS incidence per randomized woman. Secondary outcomes were live birth rate, ongoing pregnancy rate, clinical pregnancy rate and miscarriage rate. Searches (until September 2009) were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts. RESULTS: Four randomized trials entailing 570 women were included. There was evidence of a statistically significant reduction in the incidence of OHSS in the cabergoline group (OR 0.41, 95% CI 0.25-0.66) with an absolute risk reduction of 12% (95% CI 6.1-18.2%), but there was no statistically significant evidence of a reduction in severe OHSS (OR 0.50, 95% CI 0.20-1.26). There was no evidence for a difference in clinical pregnancy rate (OR 1.07, 95% CI 0.70-1.62) and miscarriage rate (OR 0.31, 95% CI 0.03-3.07). CONCLUSION: Prophylactic treatment with the dopamine agonist, cabergoline, reduces the incidence, but not the severity of OHSS, without compromising pregnancy outcomes. PMID- 20354101 TI - Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine. AB - Ablation of the mouse genes for Onecut-2 and Onecut-3 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here we examined postnatal development of these Onecut knockout mice, especially the critical period before weaning. Onecut-3 knockout mice develop normally during this period. However, Onecut-2 knockout mice fail to thrive, lagging behind their littermates in size and weight. By postnatal day (d)19, they are consistently 25 30% smaller. Onecut-2 knockout mice also have a much higher level of mortality before weaning, with only approximately 70% survival. Interestingly, Onecut-2 knockout mice that are heterozygous for the Onecut-3 knockout allele are diminished even further in their ability to thrive. They are approximately 50-60% as large as their normal-sized littermates at d19, and less than half of these mice survive to weaning. As reported previously, the Onecut-2/Onecut-3 double knockout is a perinatal lethal. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression. PMID- 20354102 TI - Identifying physiological origins of baroreflex dysfunction in salt-sensitive hypertension in the Dahl SS rat. AB - Salt-sensitive hypertension is known to be associated with dysfunction of the baroreflex control system in the Dahl salt-sensitive (SS) rat. However, neither the physiological mechanisms nor the genomic regions underlying the baroreflex dysfunction seen in this rat model are definitively known. Here, we have adopted a mathematical modeling approach to investigate the physiological and genetic origins of baroreflex dysfunction in the Dahl SS rat. We have developed a computational model of the overall baroreflex heart rate control system based on known physiological mechanisms to analyze telemetry-based blood pressure and heart rate data from two genetic strains of rat, the SS and consomic SS.13(BN), on low- and high-salt diets. With this approach, physiological parameters are estimated, unmeasured physiological variables related to the baroreflex control system are predicted, and differences in these quantities between the two strains of rat on low- and high-salt diets are detected. Specific findings include: a significant selective impairment in sympathetic gain with high-salt diet in SS rats and a protection from this impairment in SS.13(BN) rats, elevated sympathetic and parasympathetic offsets with high-salt diet in both strains, and an elevated sympathetic tone with high-salt diet in SS but not SS.13(BN) rats. In conclusion, we have associated several important physiological parameters of the baroreflex control system with chromosome 13 and have begun to identify possible physiological mechanisms underlying baroreflex impairment and hypertension in the Dahl SS rat that may be further explored in future experimental and modeling based investigation. PMID- 20354103 TI - Role of phospholipase D2/phosphatidic acid signal transduction in micro- and delta-opioid receptor endocytosis. AB - We demonstrated recently that opioid-induced activation of phospholipase D2 (PLD2) enhances mu- (MOPr) and delta-opioid receptor endocytosis/recycling and thus reduces the development of opioid receptor desensitization and tolerance. However, the mechanistic basis for the PLD2-mediated induction of opioid receptor endocytosis is currently unknown. Here we show that PLD2-generated phosphatidic acid (PA) might play a key role in facilitating the endocytosis of opioid receptors. However, PLD2-derived PA is known to be further converted to diacylglycerol (DAG) by PA phosphohydrolase (PPAP2). In fact, blocking of PA phosphohydrolase activity by propranolol or PPAP2-short interfering RNA (siRNA) transfection significantly attenuated agonist-induced opioid receptor endocytosis. The primary importance of PA-derived DAG in the induction of opioid receptor endocytosis was further supported by the finding that increasing the DAG level by inhibiting the reconversion of DAG into PA with the DAG kinase inhibitor 3-[2-(4-[bis-(4-fluorophenyl)methylene]-1-piperidinyl)ethyl]-2,3-dihydro-2-thioxo 4(1H)quinazolinone (R59949) or the addition of the synthetic cell-permeable DAG analog 1,2-dioctanoyl-sn-glycerol (DOG), further increased the agonist-induced opioid receptor endocytosis. Moreover, the addition of DOG bypasses the PLD2 siRNA- or PPAP2-siRNA-mediated impairment of DAG synthesis and resulted in a restoration of agonist-induced opioid receptor internalization. Further studies established a functional link between PA-derived DAG and the activation of p38 mitogen-activated protein kinase (MAPK) and the subsequent phosphorylation of the Rab5 effector early endosome antigen 1, which has been demonstrated recently to be required for the induction of MOPr endocytosis. Taken together, our results revealed that the regulation of opioid receptor endocytosis by PLD2 involves the conversion of its product PA to DAG resulting in an activation of the p38 MAPK pathway. PMID- 20354104 TI - In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice. AB - Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound. PMID- 20354105 TI - Quantitative prediction of intestinal metabolism in humans from a simplified intestinal availability model and empirical scaling factor. AB - This study aimed to establish a practical and convenient method of predicting intestinal availability (F(g)) in humans for highly permeable compounds at the drug discovery stage, with a focus on CYP3A4-mediated metabolism. We constructed a "simplified F(g) model," described using only metabolic parameters, assuming that passive diffusion is dominant when permeability is high and that the effect of transporters in epithelial cells is negligible. Five substrates for CYP3A4 (alprazolam, amlodipine, clonazepam, midazolam, and nifedipine) and four for both CYP3A4 and P-glycoprotein (P-gp) (nicardipine, quinidine, tacrolimus, and verapamil) were used as model compounds. Observed fraction of drug absorbed (F(a)F(g)) values for these compounds were calculated from in vivo pharmacokinetic (PK) parameters, whereas in vitro intestinal intrinsic clearance (CL(int,intestine)) was determined using human intestinal microsomes. The CL(int,intestine) for the model compounds corrected with that of midazolam was defined as CL(m,index) and incorporated into a simplified F(g) model with empirical scaling factor. Regardless of whether the compound was a P-gp substrate, the F(a)F(g) could be reasonably fitted by the simplified F(g) model, and the value of the empirical scaling factor was well estimated. These results suggest that the effects of P-gp on F(a) and F(g) are substantially minor, at least in the case of highly permeable compounds. Furthermore, liver intrinsic clearance (CL(int,liver)) can be used as a surrogate index of intestinal metabolism based on the relationship between CL(int,liver) and CL(m,index). F(g) can be easily predicted using a simplified F(g) model with the empirical scaling factor, enabling more confident selection of drug candidates with desirable PK profiles in humans. PMID- 20354106 TI - Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types. AB - This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL-15. Although DCs support IL-15-mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL-15 on memory CD8 T cells, all in vitro-derived or ex vivo-isolated DCs maintained CD8 T cells better than rIL-15 alone, and FLT-3L-DCs are the most efficient compared with GM-DCs, BM-derived macrophages, or freshly isolated DCs. Although FLT-3L-DCs were the least effective at inducing CD8 T cell proliferation, FLT-3L-DCs promoted better CD8 T cell survival and increased Bcl-2 and MCL-2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL-15Ralpha and IL-15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL-15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN-alpha enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL-15 trans-presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently. PMID- 20354107 TI - Systemic levels of G-CSF and interleukin-6 determine the angiogenic potential of bone marrow resident monocytes. AB - There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such "conditioning" signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR(-/-) and IL-6(-/-) mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP(-/-) mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes. PMID- 20354109 TI - Multiple roles for CCR2 during fracture healing. AB - Bone injury induces an inflammatory response that involves neutrophils, macrophages and other inflammatory cells. The recruitment of inflammatory cells to sites of injury occurs in response to specific signaling pathways. The CC chemokine receptor type 2 (CCR2) is crucial for recruiting macrophages, as well as regulating osteoclast function. In this study, we examined fracture healing in Ccr2-/- mice. We first demonstrated that the expression of Ccr2 transcripts and the filtration of macrophages into fracture calluses were most robust during the early phases of fracture healing. We then determined that the number of macrophages at the fracture site was significantly lower in Ccr2-/- mice compared with wild-type controls at 3 days after injury. As a result, impaired vascularization, decreased formation of callus, and delayed maturation of cartilage were observed at 7 days after injury in mutant mice. At day 14, Ccr2-/- mice had less bone in their calluses. At day 21, Ccr2-/- mice had larger calluses and more bone compared with wild-type mice, suggesting a delayed remodeling. In addition, we examined the effect of Ccr2 mutation on osteoclasts. We found that a lack of Ccr2 did not affect the number of osteoclasts within fracture calluses at 21 days after injury. However, Ccr2-/- osteoclasts exhibited a decreased ability to resorb bone compared with wild-type cells, which could contribute to the delayed remodeling of fracture calluses observed in Ccr2-/- mice. Collectively, these results indicate that a deficiency of Ccr2 reduces the infiltration of macrophages and impairs the function of osteoclasts, leading to delayed fracture healing. PMID- 20354108 TI - SirT1 in muscle physiology and disease: lessons from mouse models. AB - Sirtuin 1 (SirT1) is the largest of the seven members of the sirtuin family of class III nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, whose activation is beneficial for metabolic, neurodegenerative, inflammatory and neoplastic diseases, and augments life span in model organisms (Finkel et al., 2009; Lavu et al., 2008). In vitro studies show that SirT1 protects genome integrity and is involved in circadian physiological rhythms (Asher et al., 2008; Nakahata et al., 2008; Oberdoerffer et al., 2008). In the last few years, a fundamental role for SirT1 in the metabolism and differentiation of skeletal muscle cells has been uncovered (Fulco et al., 2003), and the use of specific transgenic or knockout SirT1 mouse models implicates it in the protection of heart muscle from oxidative and hypertrophic stresses (Alcendor et al., 2007). In this Perspective, we review the recent exciting findings that have established a key role for the 'longevity' protein SirT1 in skeletal and heart muscle physiology and disease. Furthermore, given the multiple biological functions of SirT1, we discuss the unique opportunities that SirT1 mouse models can offer to improve our integrated understanding of the metabolism, as well as the regeneration and aging-associated changes in the circadian function, of skeletal and heart muscle. PMID- 20354110 TI - Diversification of innate immune genes: lessons from the purple sea urchin. AB - Pathogen diversification can alter infection virulence, which in turn drives the evolution of host immune diversification, resulting in countermeasures for survival in this arms race. Somatic recombination of the immunoglobulin gene family members is a very effective mechanism to diversify antibodies and T-cell receptors that function in the adaptive immune system. Although mechanisms to diversify innate immune genes are not clearly understood, a seemingly unlikely source for insight into innate immune diversification may be derived from the purple sea urchin, which has recently had its genome sequenced and annotated. Although there are many differences, some characteristics of the sea urchin make for a useful tool to understand the human immune system. The sea urchin is phylogenetically related to humans although, as a group, sea urchins are evolutionarily much older than mammals. Humans require both adaptive and innate immune responses to survive immune challenges, whereas sea urchins only require innate immune functions. Genes that function in immunity tend to be members of families, and the sea urchin has several innate immune gene families. One of these is the Sp185/333 gene family with about 50 clustered members that encode a diverse array of putative immune response proteins. Understanding gene diversification in the Sp185/333 family in the sea urchin may illuminate new mechanisms of diversification that could apply to gene families that function in innate immunity in humans, such as the killer immunoglobulin-like receptor genes. PMID- 20354111 TI - The role of insulin/IGF-like signaling in C. elegans longevity and aging. AB - Aging is characterized by general physiological decline over time. A hallmark of human senescence is the onset of various age-related afflictions including neurodegeneration, cardiovascular disease and cancer. Although environmental and stochastic factors undoubtedly contribute to the increased incidence of disease with age, recent studies suggest that intrinsic genetic determinants govern both life span and overall health. Current aging research aims at achieving the 'longevity dividend', in which life span extension in humans is accomplished with a concomitant increase in the quality of life (Olshansky et al., 2007). Significant progress has been made using model organisms, especially the nematode worm Caenorhabditis elegans, to delineate the genetic and biochemical pathways involved in aging to identify strategies for therapeutic intervention in humans. In this review, we discuss how C. elegans has contributed to our understanding of insulin signaling and aging. PMID- 20354113 TI - Research that is both rigorous and useful. PMID- 20354112 TI - The zebrafish as a model for cancer. AB - For the last three decades significant parts of national science budgets, and international and private funding worldwide, have been dedicated to cancer research. This has resulted in a number of important scientific findings. Studies in tissue culture have multiplied our knowledge of cancer cell pathophysiology, mechanisms of transformation and strategies of survival of cancer cells, revealing therapeutically exploitable differences to normal cells. Rodent animal models have provided important insights on the developmental biology of cancer cells and on host responses to the transformed cells. However, the rate of death from some malignancies is still high, and the incidence of cancer is increasing in the western hemisphere. Alternative animal models are needed, where cancer cell biology, developmental biology and treatment can be studied in an integrated way. The zebrafish offers a number of features, such as its rapid development, tractable genetics, suitability for in vivo imaging and chemical screening, that make it an attractive model to cancer researchers. This Primer will provide a synopsis of the different cancer models generated by the zebrafish community to date. It will discuss the use of these models to further our understanding of the mechanisms of cancer development, and to promote drug discovery. The article was inspired by a workshop on the topic held in July 2009 in Spoleto, Italy, where a number of new zebrafish cancer models were presented. The overarching goal of the article is aimed at raising the awareness of basic researchers, as well as clinicians, to the versatility of this emerging alternative animal model of cancer. PMID- 20354114 TI - Consensus methods to identify a set of potential performance indicators for systems of emergency and urgent care. AB - OBJECTIVES: To identify a comprehensive set of indicators to enable Primary Care Trust (PCT) commissioners in England and other NHS decision-makers to monitor the performance of systems of emergency and urgent care for which they are responsible. METHODS: Using a combination of Delphi RAND methods in three successive rounds of consultation and nominal group review, we canvassed expert opinion on 70 potential indicators as good measures of system performance. The two Delphi panels consisted of senior clinicians and researchers, and urgent care leads and commissioners in PCTs and Strategic Health Authorities (SHAs). The indicators were formatted into a questionnaire according to whether they were outcome, process, structure, or equity-based measures. Participants scored each indicator on a Likert scale of 1-9 and had the opportunity to consider their scores informed by the group scores and feedback. The questionnaire was refined after each round. To ensure that the indicators rated most highly by the Delphi panels covered all dimensions of performance, the results of the Delphi were reviewed by a nominal group consisting of two researchers and three clinicians from the local health services research network (LHSR). RESULTS: Overall, the process yielded 16 candidate indicators. It also produced a core set of serious, emergency and urgent care-sensitive conditions (defined as conditions whose exacerbations should be managed by a well-performing system without admission to an inpatient bed), for use with the indicators. CONCLUSIONS: System-wide measures to monitor performance across multiple services should encourage providers to work for patient benefit in an integrated way. They will also assist commissioners to monitor and improve emergency and urgent care for their local populations. The indicators are now being calculated using routinely available data, and tested for their responsiveness to capture change over time. PMID- 20354115 TI - Complexity and whole-system change programmes. AB - OBJECTIVE: There has been growing interest in applying complexity theory to health care systems, both in policy and academic research discourses. However, its application often lacks rigour - authors discuss the properties of complex systems, state that they apply to health care and draw conclusions anchored around the idea of 'whole system change'. This paper explores the use of whole systems change in a programme to improve the delivery of unscheduled health care in Scotland. METHODS: Qualitative case-studies of five health boards in Scotland reflecting different demographics, initial performance data and progress towards meeting programme targets. RESULTS: The programme's collaborative approach was successful in moving to a culture of mutual understanding and greater awareness of the interdependencies between different functions within the hospitals. There was whole system working at the acute hospital level, leading to improved patient flows. But despite recognizing the need for whole system change overall, it proved hard to address relationships with stakeholders influencing wider out-of hospital patient flows. This was exacerbated by the structure of the programme, which was designed much more around acute patient flows. CONCLUSIONS: The programme worked well to improve performance by focusing on interdependencies within a large part of the acute care subsystem but did not have the same impact at the overall health care system level. This has important implications for the design of policy and associated programmes which seek to effect whole system reform, or at least are realistic about the magnitude of change they can achieve. PMID- 20354116 TI - Economic consequences for other family members of mental health problems in older people. AB - OBJECTIVES: We estimated the effects of poor mental health among older family members on the labour supply and incomes of younger family members living in the same household. Due to policy differences, effects for Scotland were compared with other parts of the UK. METHODS: Effects were estimated using the British Household Panel Survey (waves 1999-2006), with data from 621 older respondents and 800 younger family members. Mental health was assessed using the General Health Questionnaire (GHQ), together with self-reported presence of depression, anxiety, or other mental health problems. RESULTS: The associations between labour supply and mental ill-health were found to vary by gender and region of the UK. For men, there were larger negative effects in Scotland relative to the rest of the UK. For women, mental ill-health was associated with increased labour supply in Scotland, while in the remainder of the UK, a negative association was observed. Income losses accrued across all groups except among Scottish females, with the largest significant negative effects observed among men living in the remainder of the UK. CONCLUSIONS: Mental health problems among older family members are associated with significant labour market effects for younger family members. To reduce the economic consequences, better assessment of mental health among older people may be warranted. Further employment support for younger family members, in the form of more flexible work policies, might also serve to ameliorate economic losses. PMID- 20354117 TI - beta-Ionone enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells through Sp1-dependent upregulation of DR5 and downregulation of NF-kappaB activity. AB - beta-Ionone (ION), an end-ring analogue of beta-carotenoid, has been known to inhibit tumor cell growth and induce apoptosis in various types of cancer cells. Nevertheless, its apoptosis-related molecular mechanisms remain unclear. Here, we first investigated the molecular mechanisms by which ION sensitizes cancer cells to the therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, treatment with subtoxic concentrations of ION and TRAIL effectively inhibited cell viability in the hepatocellular carcinoma cell line Hep3B and other cancer cell lines such as colon carcinoma cell line HCT116 and leukemia cell line U937. Combined treatment with ION and TRAIL was also more effective in inducing DR5 expression, caspase activities, and apoptosis than treatment with either agent alone. ION-mediated sensitization to TRAIL was efficiently reduced by treatment with a chimeric blocking antibody or small interfering RNA specific for DR5. Electrophoretic mobility shift assay and a chromatin immunoprecipitation assay confirmed that ION treatment upregulates the binding of transcription factor Sp1 to its putative site within the DR5 promoter region, suggesting that Sp1 is an ION-responsive transcription factor. In addition, ION significantly increased hepatocellular carcinoma cell sensitivity to TRAIL by abrogating TRAIL-induced NF-kappaB activation and decreasing the expression of antiapoptotic proteins such as XIAP and IAP-1/2. Taken together, these data suggest that ION is a useful agent for TRAIL-based cancer treatments. Mol Cancer Ther; 9(4); 833-43. (c)2010 AACR. PMID- 20354118 TI - PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. AB - The Aurora family of highly related serine/threonine kinases plays a key role in the regulation of mitosis. Aurora1 and Aurora2 play important but distinct roles in the G(2) and M phases of the cell cycle and are essential for proper chromosome segregation and cell division. Overexpression and amplification of Aurora2 have been reported in different tumor types, including breast, colon, pancreatic, ovarian, and gastric cancer. PF-03814735 is a novel, potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases that is currently in phase I clinical trials for the treatment of advanced solid tumors. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. Although PF-03814735 produces significant inhibition of several other protein kinases, the predominant biochemical effects in cellular assays are consistent with inhibition of Aurora kinases. Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. These results support the clinical evaluation of PF-03814735 in cancer patients. Mol Cancer Ther; 9(4); 883-94. (c)2010 AACR. PMID- 20354119 TI - Subcellular distribution of a fluorescence-labeled combi-molecule designed to block epidermal growth factor receptor tyrosine kinase and damage DNA with a green fluorescent species. AB - To monitor the subcellular distribution of mixed epidermal growth factor (EGF) receptor (EGFR)-DNA targeting drugs termed combi-molecules, we designed AL237, a fluorescent prototype, to degrade into a green fluorescent DNA damaging species and FD105, a blue fluorescent EGFR inhibitor. Here we showed that AL237 damaged DNA in the 12.5 to 50 mumol/L range. Despite its size, it blocked EGFR phosphorylation in an enzyme assay (IC(50) = 0.27 mumol/L) and in MDA-MB468 breast cancer cells in the same concentration range as for DNA damage. This translated into inhibition of extracellular signal-regulated kinase 1/2 or BAD phosphorylation and downregulation of DNA repair proteins (XRCC1, ERCC1). Having shown that AL237 was a balanced EGFR-DNA targeting molecule, it was used as an imaging probe to show that (a) green and blue colors were primarily colocalized in the perinuclear and partially in the nucleus in EGFR- or ErbB2-expressing cells, (b) the blue fluorescence associated with FD105, but not the green, was colocalized with anti-EGFR red-labeled antibody, (c) the green fluorescence of nuclei was significantly more intense in NIH 3T3 cells expressing EGFR or ErbB2 than in their wild-type counterparts (P < 0.05). Similarly, the growth inhibitory potency of AL237 was selectively stronger in the transfectants. In summary, the results suggest that AL237 diffuses into the cells and localizes abundantly in the perinuclear region and partially in the nucleus where it degrades into EGFR and DNA targeting species. This bystander-like effect translates into high levels of DNA damage in the nucleus. Sufficient quinazoline levels are released in the cells to block EGF-induced activation of downstream signaling. Mol Cancer Ther; 9(4); 869-82. (c)2010 AACR. PMID- 20354120 TI - Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts. AB - (18)F-Fluorodeoxyglucose ((18)F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting several cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small ( approximately 1451 Da) hapten peptide with (68)Ga or (18)F to compare their specificity with (18)F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic antigen (CEA; CEACAM5)-expressing LS174T human colonic tumors and a CEA-negative tumor, or an inflammation was induced in thigh muscle. A bispecific monoclonal anti-CEA x anti-hapten antibody was given to mice, and 16 hours later, 5 MBq of (68)Ga- or (18)F-labeled hapten peptides were administered intravenously. Within 1 hour, tissues showed high and specific targeting of (68)Ga-IMP-288, with 10.7 +/- 3.6% ID/g uptake in the tumor and very low uptake in normal tissues (e.g., tumor-to blood ratio of 69.9 +/- 32.3), in a CEA-negative tumor (0.35 +/- 0.35% ID/g), and inflamed muscle (0.72 +/- 0.20% ID/g). (18)F-FDG localized efficiently in the tumor (7.42 +/- 0.20% ID/g) but also in the inflamed muscle (4.07 +/- 1.13% ID/g) and in several normal tissues; thus, pretargeted (68)Ga-IMP-288 provided better specificity and sensitivity. Positron emission tomography (PET)/computed tomography images reinforced the improved specificity of the pretargeting method. (18)F-labeled IMP-449 distributed similarly in the tumor and normal tissues as the (68)Ga-labeled IMP-288, indicating that either radiolabeled hapten peptide could be used. Thus, pretargeted immuno-PET does exceptionally well with short lived radionuclides and is a highly sensitive procedure that is more specific than (18)F-FDG-PET. Mol Cancer Ther; 9(4); 1019-27. (c)2010 AACR. PMID- 20354122 TI - AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. AB - AT7519 is a potent inhibitor of several cyclin-dependent kinases and is currently in early phase clinical development. Recently, cyclin-dependent kinases 7, 8, and 9 have been shown to regulate transcription through phosphorylation of RNA polymerase II. B-cell lymphoproliferative disorders, including chronic lymphocytic leukemia, rely on the expression of transcripts with a short half life, such as Mcl-1, Bcl-2, and XIAP, for survival. Here, we describe the characterization of AT7519 in leukemia cell lines, and compare and contrast the response in cell lines derived from solid tumors. Finally, we use these mechanistic insights to show activity in peripheral blood mononuclear cells isolated from 16 chronic lymphocytic leukemia patients. AT7519 induced apoptosis at concentrations of 100 to 700 nmol/L and was equally effective regardless of Rai stage or known prognostic markers. Short-term treatments (4-6 hours) resulted in inhibition of phosphorylation of the transcriptional marker RNA polymerase II and downregulation of the antiapoptotic protein Mcl-1, with no effect on either XIAP or Bcl-2 levels. The reduction in Mcl-1 protein level was associated with an increase in cleaved poly(ADP-ribose) polymerase. Together the data suggest AT7519 offers a promising treatment for patients with advanced B-cell leukemia. Mol Cancer Ther; 9(4); 920-8. (c)2010 AACR. PMID- 20354121 TI - Inhibition of aldose reductase prevents growth factor-induced G1-S phase transition through the AKT/phosphoinositide 3-kinase/E2F-1 pathway in human colon cancer cells. AB - Colon cancer is the leading cause of cancer death in both men and women worldwide. The deregulated cell cycle control or decreased apoptosis of normal epithelial cells leading to uncontrolled proliferation is one of the major features of tumor progression. We have previously shown that aldose reductase (AR), a NADPH-dependent aldo-keto reductase, has been shown to be involved in growth factor-induced proliferation of colon cancer cells. Herein, we report that inhibition of AR prevents epidermal growth factor (EGF)- and basic fibroblast growth factor (bFGF)-induced HT29 cell proliferation by accumulating cells at G(1) phase of cell cycle. Similar results were observed in SW480 and HCT-116 colon cancer cells. Treatment of HT29 cells with AR inhibitor, sorbinil or zopolrestat, prevented the EGF- and bFGF-induced DNA binding activity of E2F-1 and phosphorylation of retinoblastoma protein. Inhibition of AR also prevented EGF- and bFGF-induced phosphorylation of cyclin-dependent kinase (cdk)-2 and expression of G(1)-S transition regulatory proteins such as cyclin D1, cdk4, proliferating cell nuclear antigen, cyclin E, and c-myc. More importantly, inhibition of AR prevented the EGF- and bFGF-induced activation of phosphoinositide 3-kinase/AKT and reactive oxygen species generation in colon cancer cells. Further, inhibition of AR also prevented the tumor growth of human colon cancer cells in nude mouse xenografts. Collectively, these results show that AR mediates EGF- and bFGF-induced colon cancer cell proliferation by activating or expressing G(1)-S phase proteins such as E2F-1, cdks, and cyclins through the reactive oxygen species/phosphoinositide 3-kinase/AKT pathway, indicating the use of AR inhibitors in the prevention of colon carcinogenesis. Mol Cancer Ther; 9(4); 813-24. (c)2010 AACR. PMID- 20354123 TI - Phospholipase A2 activity of peroxiredoxin 6 promotes invasion and metastasis of lung cancer cells. AB - Peroxiredoxins (PRDX) are a family of thiol-dependent peroxidases. Among the six mammalian members of this family, PRDX6 is the only protein that additionally exhibits phospholipase A(2) (PLA(2)) activity. The physiologic role of this interesting PRDX6 feature is largely unknown at present. In this study, we show that PRDX6 increases the metastatic potential of lung cancer cells. Functional analyses of the enzymatic activities of PRDX6, using specific pharmacologic inhibitors and mutagenesis studies, reveal that both peroxidase and PLA(2) activities are required for metastasis. Specifically, peroxidase activity facilitates the growth of cancer cells, and PLA(2) activity promotes invasiveness. Further investigation of the latter event discloses that PLA(2) activity promotes accumulation of arachidonic acid, which, in turn, induces the invasive pathway involving p38 kinase, phosphoinositide 3-kinase, Akt, and urokinase-type plasminogen activator. This study is the first to define the functions of the enzymatic activities of PRDX6 in metastasis and to show the involvement of arachidonic acid in PRDX6 action in intact cells. These novel findings provide a significant step toward elucidating the role of PRDX6 in cancer and the mechanism of its action. Mol Cancer Ther; 9(4); 825-32. (c)2010 AACR. PMID- 20354124 TI - Regulatory divergence in Drosophila revealed by mRNA-seq. AB - The regulation of gene expression is critical for organismal function and is an important source of phenotypic diversity between species. Understanding the genetic and molecular mechanisms responsible for regulatory divergence is therefore expected to provide insight into evolutionary change. Using deep sequencing, we quantified total and allele-specific mRNA expression levels genome wide in two closely related Drosophila species (D. melanogaster and D. sechellia) and their F(1) hybrids. We show that 78% of expressed genes have divergent expression between species, and that cis- and trans-regulatory divergence affects 51% and 66% of expressed genes, respectively, with 35% of genes showing evidence of both. This is a relatively larger contribution of trans-regulatory divergence than was expected based on prior studies, and may result from the unique demographic history of D. sechellia. Genes with antagonistic cis- and trans regulatory changes were more likely to be misexpressed in hybrids, consistent with the idea that such regulatory changes contribute to hybrid incompatibilities. In addition, cis-regulatory differences contributed more to divergent expression of genes that showed additive rather than nonadditive inheritance. A correlation between sequence similarity and the conservation of cis-regulatory activity was also observed that appears to be a general feature of regulatory evolution. Finally, we examined regulatory divergence that may have contributed to the evolution of a specific trait--divergent feeding behavior in D. sechellia. Overall, this study illustrates the power of mRNA sequencing for investigating regulatory evolution, provides novel insight into the evolution of gene expression in Drosophila, and reveals general trends that are likely to extend to other species. PMID- 20354126 TI - Subtype-specific risk of testicular tumors among immigrants and their descendants in Sweden, 1960 to 2007. AB - BACKGROUND: Testicular cancer is the most common cancer among young male adults in several populations. We compared subtype-specific risk of testicular cancer among migrants and their descendants to that of Swedish-born men to elucidate importance of genetic and environmental factors in testicular cancer etiology and the potential timing of exposures. METHODS: We followed a nationwide cohort of 3.6 million men ages 15 to 54 years between 1960 and 2007 through linkage between Swedish National Registers. Incidence rate ratio (IRR) adjusted for age and calendar year with 95% confidence intervals (CI) was estimated using Poisson regression. RESULTS: A total of 5,801 cases of testicular cancer occurred during 80 million person-years of follow-up. Compared with Swedish-born men, first generation immigrants from low-risk countries had a lower risk (IRR, 0.43; 95% CI, 0.38-0.49) and first-generation immigrants from high-risk countries had a higher risk (IRR, 1.61; 95% CI, 1.42-1.83) of testicular cancer. The risk among first-generation immigrants varied remarkably by birthplace, reflecting the risk in their countries of birth. The risk of seminomas was statistically significantly modified by age at immigration and duration of residence among immigrants born in high-risk areas. We observed a statistically significantly convergence of risk among second-generation immigrants toward the risk in Sweden (IRR, 1.02; 95% CI, 0.93-1.12). The risk among second-generation immigrants was not affected by the duration of stay of their mothers in Sweden before pregnancy. CONCLUSIONS: Our study provides evidence that life-style and environmental factors play an important role in the etiology of testicular cancer. PMID- 20354125 TI - Longitudinal predictors of nonadherence to maintenance of mammography. AB - BACKGROUND: Regular adherence to screening mammography, also known as maintenance of mammography, reduces breast cancer morbidity and mortality. However, mammography maintenance is uncommon and little is known about why women do not maintain regular screening schedules. We investigated longitudinal predictors of women not maintaining adherence. METHODS: Participants were insured women enrolled in an intervention trial who had screening mammograms 8 to 9 months before study enrollment (n = 1,493). Data were collected from 2003 to 2008. We used discrete event history analysis to model nonadherence to mammography maintenance over three successive annual screening intervals (+ 2 months). RESULTS: Most (54%) women did not maintain screening adherence over 3 years. Women who did not maintain adherence were more likely to be ages 40 to 49 years, rate their health fair or poor, be less satisfied with their last mammography experiences, report one or more barriers to getting mammograms, be less than completely confident about getting their next mammograms (lower self-efficacy), or have weaker behavioral intentions. The odds of not maintaining adherence decreased over time. DISCUSSION: Although great strides have been achieved in increasing the proportion of women who have received mammograms, most women still are not maintaining regular mammography use over time. Our findings provide insights into targets for future mammography maintenance interventions. PMID- 20354127 TI - Tobacco smoke exposure in nonsmoking hospitality workers before and after a state smoking ban. AB - Secondhand smoke exposure is estimated to account for 3,000 cancer deaths per year. Although several countries and states in the United States have passed comprehensive smoke-free laws to protect all employees, a significant number of workers are still not protected. The purpose of this study was to determine the effects of passing a comprehensive smoking ban that included bars and restaurants on biomarkers of nicotine and carcinogen exposure. The urines of nonsmoking employees (n = 24) of bars and restaurants that allowed smoking before the smoke free law were analyzed before and after the law was passed in Minnesota. The results showed significant reductions in both total cotinine and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (free plus glucuronidated) after the ban was instituted. These results provide further support for the importance of protecting employees working in all venues. PMID- 20354128 TI - Temporal trends in geographic disparities in small-area breast cancer incidence and mortality, 1988 to 2005. AB - BACKGROUND: A goal of Healthy People 2010 was to reduce health disparities. We determined the extent of reductions in geographic disparities in five breast cancer screening indicators. METHODS: We examined the extent of reductions in geographic disparities in five breast cancer screening indicators using data about women ages 40 years and older from 200 counties in the 1988 to 2005 Surveillance, Epidemiology, and End Results Program database. County-level trends in five breast cancer indicators (in situ, stage I, lymph node-positive, locally advanced, and mortality) were summarized using the estimated annual percentage change. Observed county rates were smoothed using hierarchical Bayesian spatiotemporal methods to calculate measures of absolute and relative geographic disparity and their changes over time. RESULTS: For in situ breast cancer, absolute disparity increased 93.7% during 1988 to 2005. Relative disparity declined 61.5% during the entire study period. Absolute and relative disparity for stage I breast cancer declined 18.5% and 41.4%, respectively. Absolute disparity for lymph node-positive breast cancer declined 37.9% during the study period, whereas relative disparity declined 17.6%. Absolute disparity for locally advanced breast cancer declined 66.5%, whereas relative disparity declined 17.8% during the study period. Absolute disparity in breast cancer mortality declined 60.5%, whereas relative disparity declined 19.8%. CONCLUSIONS: Absolute and relative geographic disparities narrowed over time for all breast cancer indicators except for in situ breast cancer. IMPACT: Progress has been made toward reducing geographic disparities in breast cancer outcomes, particularly in advanced-stage breast cancer incidence and mortality rates, although disparities remain. PMID- 20354133 TI - Physicians' awareness and attitudes toward decision aids for patients with cancer. AB - PURPOSE: Patient decision aids are interventions designed to help patients make deliberative choices about their treatment options and have been shown to significantly improve patient outcomes. Although considered optimal, decision aids are not widely used in clinical practice for cancer treatment. The objectives of this study are to determine physicians' awareness and use of decision aids, physicians' perceptions of the major barriers to the use of decision aids, and physician characteristics predictive of use of decision aids in clinical practice. METHODS: A population-based survey was mailed to general surgeons, medical oncologists, and radiation oncologists. RESULTS: The survey was mailed to 878 physicians, and the overall response rate to the survey was 64.5%. The majority of the participants were male and working in community hospitals for more than 10 years. Overall, 69% of the respondents were aware of decision aids, and 46% were aware of decision aids relevant to their practice. However, only 24% were currently using decision aids. The main barriers to the use of decision aids were reported as lack of awareness, lack of resources, and lack of time. Multivariate analysis showed specialty to be the only physician characteristic influencing the use of decision aids. CONCLUSION: Approximately one third of physicians treating cancer patients are not aware of what decision aids are, and only 24% are currently using decision aids in clinical practice. Strategies to increase physician awareness about decision aids and to implement these tools into clinical practice are important. PMID- 20354132 TI - Phase I combination trial of lenalidomide and azacitidine in patients with higher risk myelodysplastic syndromes. AB - PURPOSE: Lenalidomide and azacitidine are active in patients with lower- and higher-risk myelodysplastic syndromes (MDS). These agents may complement each other by targeting both the bone marrow microenvironment and hypomethylating action on the malignant clone. PATIENTS AND METHODS: This phase I trial explored the safety of combination therapy in patients with higher-risk MDS. Response and characterization of molecular and methylation status of responders were secondary objectives. Patients were enrolled using a 3 + 3 dose escalation. Cycles lasted 28 days, and patients received a maximum of seven cycles. RESULTS: Of 18 patients enrolled, median age was 68 years (range, 52 to 78 years), interval from diagnosis was 5 weeks (range, 2 to 106 weeks), and follow-up was 7 months (range, 1 to 26 months). International Prognostic Scoring System categories were intermediate 1 (n = 2), intermediate 2 (n = 10), and high (n = 6). No dose limiting toxicities occurred, and a maximum-tolerated dose was not reached. Grades 3 to 4 nonhematologic toxicities (> 1) included febrile neutropenia (n = 5), cardiac (n = 2), and CNS hemorrhage (n = 2). Median absolute neutrophil count decrease was 26%, and platelet decrease was 1% (mean, 24%). The overall response rate was 67%: eight patients (44%) had a complete response (CR); three patients (17%) had hematologic improvement; one patient (6%) had marrow CR. Patients achieving CR were more likely to have normal cytogenetics and lower methylation levels. CONCLUSION: The combination of lenalidomide and azacitidine is well tolerated with encouraging clinical activity. The go-forward dose is azacitidine 75 mg/m(2) on days 1 through 5 and lenalidomide 10 mg on days 1 through 21. PMID- 20354135 TI - Tau-tubulin kinase 1 enhances prefibrillar tau aggregation and motor neuron degeneration in P301L FTDP-17 tau-mutant mice. AB - Tau-tubulin kinase-1 (TTBK1) phosphorylates microtubule-associated protein tau at specific serine/threonine residues found in paired helical filaments (PHFs), and its expression is up-regulated in the brain in Alzheimer disease, suggesting its role in tauopathy pathogenesis. To understand the effects of TTBK1 on tauopathy in vivo, we have developed bigenic mice overexpressing full-length TTBK1 and the P301L tau mutant. The bigenic mice show enhanced tau phosphorylation at multiple sites (AT8, 12E8, PHF-1, and pS422), tauC3-immunoreactive tau fragmentation, and accumulation of tau aggregates in cortical and hippocampal neurons at 12-13 mo of age. However, the phosphorylated tau aggregates were predominantly sarkosyl soluble and migrated in the light sucrose density fraction after discontinuous sucrose gradient ultracentrifugation, which suggests that they form small oligomers. The bigenic mice show significant locomotor dysfunction as determined by both rotorod and grip strength tests, as well as enhanced loss of motor neurons in the L4-L5 spinal cord. This neuronal dysfunction and degeneration was associated with increased levels of tau oligomers, cyclin-dependent protein kinase 5 activators p35 and p25, and pY216 phosphorylated glycogen synthase kinase 3-beta. These data suggest that TTBK1 up-regulation enhances tau phosphorylation and oligomerization, whose toxicity results in enhanced neurodegeneration and locomotor dysfunction in a tauopathy animal model. PMID- 20354134 TI - Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3 mediated oncogenesis. AB - Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention. PMID- 20354136 TI - Robust activation of the human but not mouse telomerase gene during the induction of pluripotency. AB - Pluripotent stem cells (PSCs) express telomerase and have unlimited proliferative potential. To study telomerase activation during reprogramming, 3 classes of embryonic stem cell (ESC)-like clones were isolated from mouse fibroblasts containing a transgenic hTERT reporter. Class I expressed few pluripotency markers, whereas class II contained many, but not Oct4, Nanog, and Sox2. Neither class of cells differentiated efficiently. Class III cells, the fully reprogrammed induced PSCs (iPSCs), expressed all pluripotency markers, formed teratomas indistinguishable from those of mESCs, and underwent efficient osteogenic differentiation in vitro. Interestingly, whereas the endogenous mTERT gene expression was only moderately increased during reprogramming, the hTERT promoter was strongly activated in class II cells and was further elevated in class III cells. Treatment of class II cells with chemical inhibitors of MEKs and glycogen synthase kinase 3 resulted in their further reprogramming into class III cells, accompanied by a strong activation of hTERT promoter. In reprogrammed human cells, the endogenous telomerase level, although variable among different clones, was dramatically elevated. Only in cells with the highest telomerase were telomeres restored to the lengths in hESCs. Our data, for the first time, demonstrated that the hTERT promoter was strongly activated in discrete steps, revealing a critical difference in human and mouse cell reprogramming. Because telomere elongation is crucial for self-renewal of hPSCs and replicative aging of their differentiated progeny, these findings have important implications in the generation and applications of iPSCs. PMID- 20354137 TI - Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes. AB - A transcriptome analysis compared gene expression in human bone biopsy samples taken from lumbar spine and iliac crest, sites that experience high and low levels of mechanical stress, respectively. The analysis revealed that the zinc finger protein of cerebellum (Zic) family member transcription factor Zic1 was the most up-regulated gene in the lumbar spine (202-fold; P<10(-7)) in comparison with the iliac crest. Software analysis of differential gene expression in the biopsy samples identified the ciliary-related proteins PATCH1 and GLI-Kruppel family members Gli1 and Gli3 as part of a potential molecular network associated with Zic1. RT-PCR confirmed the expression of Zic1, Gli1, and Gli3 and other related key signaling mediators in osteoblastic cells and osteocytes in vitro. Zic1 was immunolocalized in the cytosol and nucleus of the murine osteocyte cell line MLO-Y4 and osteoblast-like cells MC3T3-E1 and in primary rat osteoblasts. MLO-Y4 cells subjected to prolonged oscillatory fluid flow showed increased localization of Zic1 in the nucleus with diminished levels in the cytosol, but no such changes were seen in MC3T3-E1 cells. A shear stress-induced increase in T cell factor/lymphoid enhancer factor transcriptional activity was abolished by Zic1 gene silencing. These results suggest that Zic1, perhaps together with Gli1 and Gli3, may act as a link between mechanosensing and Wnt signaling. We conclude that Zic1, a neural developmental transcription factor, plays an important role in shear flow mechanotransduction in osteocytes. PMID- 20354138 TI - New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells. AB - Medulloblastoma is the most common malignant brain tumor in children, and despite improvements in the overall survival rate, it still lacks an effective treatment. Src plays an important role in cancer, and recently high Src activity was documented in medulloblastoma. In this report, we examined the effects of novel pyrazolo-[3,4-d]-pyrimidine derivative Src inhibitors in medulloblastoma. By MTS assay, we showed that the pyrimidine derivatives indicated as S7, S29, and SI163 greatly reduce the growth rate of medulloblastoma cells by inhibiting Src phosphorylation, compared with HT22 non-neoplastic nerve cells. These compounds also halt cells in the G(2)/M phase, and this effect likely occurs through the regulation of cdc2 and CDC25C phosphorylation, as shown by Western blot. Moreover, the exposure to pyrimidine derivatives induces apoptosis, assayed by the supravital propidium iodide assay, through modulation of the apoptotic proteins Bax and Bcl2, and inhibits tumor growth in vivo in a mouse model. Notably, S7, S29, and SI163 show major inhibitory effects on medulloblastoma cell growth compared with the chemotherapeutic agents cisplatin and etoposide. In conclusion, our results suggest that S7, S29, and SI163 could be novel attractive candidates for the treatment of medulloblastoma or tumors characterized by high Src activity. PMID- 20354139 TI - Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. AB - In atherogenesis, macrophage foam cell formation is modulated by pathways involving both the uptake and efflux of cholesterol. We recently showed that interleukin-10 (IL-10) modulates lipid metabolism by enhancing both uptake and efflux of cholesterol in macrophages. However, the mechanistic details of these properties in vivo have been unclear. Thus, the purpose of this study was to determine whether expression of IL-10 in macrophages would alter susceptibility to atherosclerosis and whether IL-10 exerts its antiatherosclerotic properties by modulating lipid metabolism in macrophages. We utilized a macrophage-specific retroviral vector that allows long-term in vivo expression of IL-10 in macrophages through transplantation of retrovirally transduced bone marrow cells (BMCs). IL-10 expressed by macrophages derived from transduced BMCs inhibited atherosclerosis in LDLR(-/-) mice by reducing cholesteryl ester accumulation in atherosclerotic sites. Experiments with primary macrophages indicated that macrophage source of IL-10 stimulated both the uptake (by up-regulating scavenger receptors) and efflux of cholesterol (by activating the PPARgamma-LXR-ABCA1/ABCG1 pathway), thereby reducing inflammation and apoptosis in atherosclerosis. These findings indicate that BMC-transduced macrophage IL-10 production can act as a strong antiatherogenic agent, and they highlight a novel antiatherosclerotic therapy using a simple, yet effective, stem cell transduction system that facilitates long-term expression of IL-10 in macrophages. PMID- 20354140 TI - Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis. AB - Loss of the fumarate hydratase (FH) tumor suppressor gene results in the development of benign tumors that rarely, but regrettably, progress to very aggressive cancers. Using mouse embryo fibroblasts (MEFs) to model transformation, we found that fh knockdown results in increased expression of the met oncogene-encoded tyrosine kinase receptor through hypoxia-inducible factor (hif) stabilization. MET-increased expression was alone able to stabilize hif, thus establishing a feed forward loop that might enforce tumor progression. The fh-defective MEFs showed increased motility and protection from apoptosis. Motility, but not survival, relied on hif-1alpha and was greatly enhanced by MET ligand hepatocyte growth factor. Met cooperated with a weakly oncogenic ras in making MEFs transformed and tumorigenic, as shown by in vitro and in vivo assays. Loss of fh was not equally effective by itself but enhanced the transformed and tumorigenic phenotype induced by ras and MET. Consistently, the rescue of fumarase expression abrogated the motogenic and transformed phenotype of fh defective MEFs. In conclusion, the data suggest that the progression of tumors where FH is lost might be boosted by activation of the MET oncogene, which is able to drive cell-autonomous tumor progression and is a strong candidate for targeted therapy. PMID- 20354141 TI - Facilitative plasma membrane transporters function during ER transit. AB - Although biochemical studies suggested a high permeability of the endoplasmic reticulum (ER) membrane for small molecules, proteomics identified few specialized ER transporters. To test functionality of transporters during ER passage, we tested whether glucose transporters (GLUTs, SGLTs) destined for the plasma membrane are active during ER transit. HepG2 cells were characterized by low-affinity ER transport activity, suggesting that ER uptake is protein mediated. The much-reduced capacity of HEK293T cells to take up glucose across the plasma membrane correlated with low ER transport. Ectopic expression of GLUT1, -2, -4, or -9 induced GLUT isoform-specific ER transport activity in HEK293T cells. In contrast, the Na(+)-glucose cotransporter SGLT1 mediated efficient plasma membrane glucose transport but no detectable ER uptake, probably because of lack of a sufficient sodium gradient across the ER membrane. In conclusion, we demonstrate that GLUTs are sufficient for mediating ER glucose transport en route to the plasma membrane. Because of the low volume of the ER, trace amounts of these uniporters contribute to ER solute import during ER transit, while uniporters and cation-coupled transporters carry out export from the ER, together potentially explaining the low selectivity of ER transport. Expression levels and residence time of transporters in the ER, as well as their coupling mechanisms, could be key determinants of ER permeability. PMID- 20354142 TI - Proteomic identification of sorting nexin 6 as a negative regulator of BACE1 mediated APP processing. AB - The beta-site APP cleaving enzyme-1 (BACE1) mediates the first cleavage of the beta-amyloid precursor protein (APP) to yield the amyloid beta-peptide (Abeta), a key pathogenic agent in Alzheimer's disease (AD). Using a proteomic approach based on in-cell chemical cross-linking and tandem affinity purification (TAP), we herein identify sorting nexin 6 (SNX6) as a BACE1-associated protein. SNX6, a PX domain protein, is a putative component of retromer, a multiprotein cargo complex that mediates the retrograde trafficking of the cation-independent mannose-6-phosphate receptor (CI-MPR) and sortilin. RNA interference suppression of SNX6 increased BACE1-dependent secretion of soluble APP (sAPPbeta) and cell associated fragments (C99), resulting in increased Abeta secretion. Furthermore, SNX6 reduction led to elevated steady-state BACE1 levels as well as increased retrograde transport of BACE1 in the endocytic pathway, suggesting that SNX6 modulates the retrograde trafficking and basal levels of BACE1, thereby regulating BACE1-mediated APP processing and Abeta biogenesis. Our study identifies a novel cellular pathway by which SNX6 negatively modulates BACE1 mediated cleavage of APP. PMID- 20354143 TI - The death effector domain protein PEA-15 negatively regulates T-cell receptor signaling. AB - PEA-15 is a death effector domain-containing phosphoprotein that binds ERK and restricts it to the cytoplasm. PEA-15 also binds to FADD and thereby blocks apoptosis induced by death receptors. Abnormal expression of PEA-15 is associated with type II diabetes and some cancers; however, its physiological function remains unclear. To determine the function of PEA-15 in vivo, we used C57BL/6 mice in which the PEA-15 coding region was deleted. We thereby found that PEA-15 regulates T-cell proliferation. PEA-15-null mice did not have altered thymic or splenic lymphocyte cellularity or differentiation. However, PEA-15 deficient T cells had increased CD3/CD28-induced nuclear translocation of ERK and increased activation of IL-2 transcription and secretion in comparison to control wild-type littermates. Indeed, activation of the T-cell receptor in wild-type mice caused PEA-15 release of ERK. In contrast, overexpression of PEA-15 in Jurkat T cells blocked nuclear translocation of ERK and IL-2 transcription. Finally, PEA-15-null T cells showed increased IL-2 dependent proliferation on stimulation. No differences in T cell susceptibility to apoptosis were found. Thus, PEA-15 is a novel player in T-cell homeostasis. As such this work may have far reaching implications in understanding how the immune response is controlled. PMID- 20354144 TI - Expression of masticatory-specific isoforms of myosin heavy-chain, myosin-binding protein-C and tropomyosin in muscle fibers and satellite cell cultures of cat masticatory muscle. AB - We test the hypothesis that cat jaw satellite cells belong to a distinct lineage preprogrammed to express masticatory-specific isoforms of myosin heavy-chain (m MyHC), myosin-binding protein-C (m-MBP-C), and tropomyosin (m-Tm) during myogenesis in vitro. A monoclonal antibody (MAb) against m-MyHC and MAbs raised here against cat m-MBP-C and m-Tm were used to stain cryostat sections of cat masseter muscle and cultured myotubes derived from satellite cells of cat temporalis and limb muscles, using peroxidase immunohistochemistry. MAbs against m-MBP-C bound purified m-MBP-C in Western blots. MAbs against m-Tm failed to react with m-Tm in Western blots, but reacted with native m-Tm in gel electrophoresis-derived ELISA. In cat masseter sections, MAbs against m-MyHC, m MBP-C, and m-Tm stained all masticatory fibers, but not the jaw-slow fibers. Cat jaw and limb muscle cultures mature significantly more slowly relative to rodent cultures. However, at 3 weeks, all three MAbs extensively stained temporalis myotubes, whereas they apparently stained isolated myotubes weakly in cat limb and rat jaw cultures. We conclude that satellite cells of masticatory fibers are preprogrammed to express these isoforms during myogenesis in vitro. These results consolidate the notion that masticatory and limb muscle allotypes are distinct. PMID- 20354145 TI - Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain. AB - In rodents, the Otx2 gene is expressed in the diencephalon, mesencephalon, and cerebellum and is crucial for the development of these brain regions. Together with Otx1, Otx2 is known to cooperate with other genes to develop the caudal forebrain and, further, Otx1 is also involved in differentiation of young neurons of the deeper cortical layers. We have studied the spatial and temporal expression of the two homeobox genes OTX2 and OTX1 in human fetal brains from 7 to 14 weeks postconception by in situ hybridization and immunohistochemistry. OTX2 was expressed in the diencephalon, mesencephalon, and choroid plexus, with a minor expression in the basal telencephalon. The expression of OTX2 in the hippocampal anlage was strong, with no expression in the adjacent neocortex. Contrarily, the OTX1 expression was predominantly located in the proliferative zones of the neocortex. At later stages, the OTX2 protein was found in the subcommissural organ, pineal gland, and cerebellum. The early expression of OTX2 and OTX1 in proliferative cell layers of the human fetal brain supports the concept that these homeobox genes are important in neuronal cell development and differentiation: OTX1 primarily in the neocortex, and OTX2 in the archicortex, diencephalon, rostral brain stem, and cerebellum. PMID- 20354146 TI - Variable expression of nuclear receptor coactivator 4 (NcoA4) during mouse embryonic development. AB - Human nuclear receptor coactivator 4 (NcoA4) amplifies the activity of several ligand-activated nuclear transcription factors, including the aryl hydrocarbon receptor (AhR) and androgen receptor (AR). Because these receptors exert important regulatory effects during development, with AhR ubiquitously expressed after embryonic day 9.5 (E9.5) and AR expressed from E12 onward, we examined NcoA4 expression in mouse embryos from E9.5 to E17.5. Full-length NcoA4 transcript was detected by RT-PCR at all embryonic stages and in all adult mouse tissues examined, although a novel splice variant was also detected. Western blot analysis indicated the expression of full-length NcoA4 protein, which was more highly expressed at later (E15.5-E17.5) embryonic stages. NcoA4 protein was also present at varying levels in all adult mouse tissues examined. A dynamic expression profile for NcoA4 during early development was indicated by immunohistochemistry in cardiac, hepatic, and lung tissue. Unlike human NcoA4, murine NcoA4 lacks an LXXLL motif, which has been implicated in the interaction with AR. Overexpression of murine NcoA4 augmented the transcriptional activity of AhR by 5-fold and AR by only 1.5-fold in COS cells. These studies demonstrate ubiquitous NcoA4 expression throughout development and suggest that this coactivator may play a role in modulating nuclear receptor activity, particularly that of the AhR, during development. PMID- 20354147 TI - In situ fluorescence imaging of myelination. AB - We describe a novel fluorescent dye, 3-(4-aminophenyl)-2H-chromen-2-one (termed case myelin compound or CMC), that can be used for in situ fluorescent imaging of myelin in the vertebrate nervous system. When administered via intravenous injection into the tail vein, CMC selectively stained large bundles of myelinated fibers in both the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS, CMC readily entered the brain and selectively localized in myelinated regions such as the corpus callosum and cerebellum. CMC also selectively stained myelinated nerves in the PNS. The staining patterns of CMC in a hypermyelinated mouse model were consistent with immunohistochemical staining. Similar to immunohistochemical staining, CMC selectively bound to myelin sheaths present in the white matter tracts. Unlike CMC, conventional antibody staining for myelin basic protein also stained oligodendrocyte cytoplasm in the striatum as well as granule layers in the cerebellum. In vivo application of CMC was also demonstrated by fluorescence imaging of myelinated nerves in the PNS. PMID- 20354148 TI - Bone marrow-derived endothelial progenitor cells and endothelial cells may contribute to endothelial repair in the kidney immediately after ischemia reperfusion. AB - In ischemic acute kidney injury, renal blood flow is decreased. We have previously shown that reperfused, transplanted kidneys exhibited ischemic injury to vascular endothelium and that preservation of peritubular capillary endothelial integrity may be critical to recovery from ischemic injury. We hypothesized that bone marrow-derived (BMD) endothelial progenitor cells (EPCs) might play an important role in renal functional recovery after ischemia. We tested this hypothesis in recipients of cadaveric renal allografts before and for 2 weeks after transplantation. We found that the numbers of circulating CD34 positive EPCs and CD146-positive endothelial cells (ECs) decreased immediately after ischemia-reperfusion. In renal allograft tissues obtained 1 hr after reperfusion, CD34-positive cells were more frequently observed along the endothelial lining of peritubular capillaries compared with non-ischemic controls. Moreover, 0-17.5% of peritubular capillary ECs were of recipient origin. In contrast, only 0.1-0.7% of tubule cells were of recipient origin. Repeat graft biopsy samples obtained 35 and 73 days after transplant did not contain capillary ECs of recipient origin, whereas 1.4% and 12.1% of tubule cells, respectively, were of recipient origin. These findings suggest that BMD EPCs and ECs may contribute to endothelial repair immediately after ischemia reperfusion. PMID- 20354149 TI - Expression of aryl hydrocarbon receptor in human placentas and fetal tissues. AB - The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates many biological processes, including fetal development. In this study, we examined AhR protein expression in human placentas from normal (N) and severe preeclamptic (sPE) pregnancies, as well as human fetal tissues from the second trimester of pregnancy, using immunohistochemistry and/or Western blot analysis. In the placentas, the AhR immunoreactivity was present primarily in syncytiotrophoblasts. The AhR staining was also seen in endothelium of large blood vessels in villi and endothelium of umbilical cord arteries and veins. No difference in AhR protein levels was found between N and sPE placentas. In fetal tissues, the AhR immunoreactivity was localized in lung, kidney, esophagus, pancreas, liver, testicle, thymus gland, retina, and choroid, mainly in epithelial cells, whereas it was absent in heart, brain, sclera, and thoracic aorta. These findings suggest that the AhR plays a critical role in syncytiotrophoblasts of human placentas and epithelium of many fetal organs. These data also imply that human placentas and those fetal organs with high AhR expression (e.g., lung, kidney, liver, pancreas, and thymus gland) during fetal development are highly susceptible to environmental toxicants such as dioxin. PMID- 20354151 TI - Binding and release of the 6S transcriptional control RNA. AB - 6S RNA is an important noncoding RNA that regulates eubacterial transcription. In Escherichia coli this RNA binds to the sigma(70) RNA polymerase holoenzyme and is released by the synthesis of a short product RNA. In order to determine how binding and release are controlled by the 6S RNA sequence, we used in vitro selection to screen a high diversity library containing approximately 4 x 10(12) sequences for functional 6S RNA variants. Residues critical for binding were found to be located in a "-35" region upstream of the 6S RNA transcription bubble mimic structure. Mutating these phylogenetically conserved residues invariably led to decreases in binding and removing them abolished binding, implicating these nucleotides in a biologically important interaction with the Esigma(70) complex. Interestingly, mutation of phylogenetically conserved "-10" residues that were also upstream of the site of pRNA synthesis was found to influence 6S RNA release rates in addition to modulating -35 binding. These results indicate how 6S RNA -35 binding to sigma(70) RNA polymerase holoenzyme can regulate expression from "strong" and "weak" -35 DNA promoters and suggest that 6S RNA release rates have been fine tuned over evolutionary time so as to correctly regulate cellular levels of transcription. PMID- 20354150 TI - Dicer's helicase domain is required for accumulation of some, but not all, C. elegans endogenous siRNAs. AB - Years after the discovery that Dicer is a key enzyme in gene silencing, the role of its helicase domain remains enigmatic. Here we show that this domain is critical for accumulation of certain endogenous small interfering RNAs (endo siRNAs) in Caenorhabditis elegans. The domain is required for the production of the direct products of Dicer, or primary endo-siRNAs, and consequently affects levels of downstream intermediates, the secondary endo-siRNAs. Consistent with the role of endo-siRNAs in silencing, their loss correlates with an increase in cognate mRNA levels. We find that the helicase domain of Dicer is not necessary for microRNA (miRNA) processing, or RNA interference following exposure to exogenous double-stranded RNA. Comparisons of wild-type and helicase-defective strains using deep-sequencing analyses show that the helicase domain is required by a subset of annotated endo-siRNAs, in particular, those associated with the slightly longer 26-nucleotide small RNA species containing a 5' guanosine. PMID- 20354152 TI - On the role of Hoogsteen:Hoogsteen interactions in RNA: ab initio investigations of structures and energies. AB - We use a combination of database analysis and quantum chemical studies to investigate the role of cis and trans Hoogsteen:Hoogsteen (H:H) base pairs and associated higher-order structures in RNA. We add three new examples to the list of previously identified base-pair combinations belonging to these families and, in addition to contextual classification and characterization of their structural and energetic features, we compare their interbase interaction energies and propensities toward participation in triplets and quartets. We find that some base pairs, which are nonplanar in their isolated minimum energy geometries, attain planarity and stability upon triplet formation. A:A H:H trans is the most frequent H:H combination in RNA structures. This base pair occurs at many distinct positions in known rRNA structures, where it helps in the interaction of ribosomal domains in the 50S subunit. It is also present as a part of tertiary interaction in tRNA structures. Although quantum chemical studies suggest an intrinsically nonplanar geometry for this base pair in isolated form, it has the tendency to attain planar geometry in RNA crystal structures by forming higher order tertiary interactions or in the presence of additional base-phosphate interactions. The tendency of this base pair to form such additional interactions may be helpful in bringing together different segments of RNA, thus making it suitable for the role of facilitator for RNA folding. This also explains the high occurrence frequency of this base pair among all H:H interactions. PMID- 20354153 TI - Induced fit or conformational selection for RNA/U1A folding. AB - The hairpin II of U1 snRNA can bind U1A protein with high affinity and specificity. NMR spectra suggest that the loop region of apo-RNA is largely unstructured and undergoes a transition from unstructured to well-folded upon U1Abinding. However, the mechanism that RNA folding coupled protein binding is poorly understood. To get an insight into the mechanism, we have performed explicit-solvent molecular dynamics (MD) to study the folding kinetics of bound RNA and apo-RNA. Room-temperature MD simulations suggest that the conformation of bound RNA has significant adjustment and becomes more stable upon U1A binding. Kinetic analysis of high-temperature MD simulations shows that bound RNA and apo RNA unfold via a two-state process, respectively. Both kinetics and free energy landscape analyses indicate that bound RNA folds in the order of RNA contracting, U1A binding, and tertiary folding. The predicted Phi-values suggest that A8, C10, A11, and G16 are key bases for bound RNA folding. Mutant Arg52Gln analysis shows that electrostatic interaction and hydrogen bonds between RNA and U1A (Arg52Gln) decrease. These results are in qualitative agreement with experiments. Furthermore, this method could be used in other studies about biomolecule folding upon receptor binding. PMID- 20354154 TI - Characterization of the human tRNA-guanine transglycosylase: confirmation of the heterodimeric subunit structure. AB - The eukaryotic tRNA-guanine transglycosylase (TGT) has been reported to exist as a heterodimer, in contrast to the homodimeric eubacterial TGT. While ubiquitin specific protease 14 (USP14) has been proposed to act as a regulatory subunit of the eukaryotic TGT, the mouse TGT has recently been shown to be a queuine tRNA ribosyltransferase 1 (QTRT1, eubacterial TGT homolog).queuine tRNA ribosyltransferase domain-containing 1 (QTRTD1) heterodimer. We find that human QTRTD1 (hQTRTD1) co-purifies with polyhistidine-tagged human QTRT1 (ht-hQTRT1) via Ni(2+) affinity chromatography. Cross-linking experiments, mass spectrometry, and size exclusion chromatography results are consistent with the two proteins existing as a heterodimer. We have not been able to observe co-purification and/or association between hQTRT1 and USP14 when co-expressed in Escherichia coli. More importantly, under our experimental conditions, the transglycosylase activity of hQTRT1 is only observed when hQTRT1 and hQTRTD1 have been co expressed and co-purified. Kinetic characterization of the human TGT (hQTRT1.hQTRTD1) using human tRNA(Tyr) and guanine shows catalytic efficiency (k(cat)/K(M)) similar to that of the E. coli TGT. Furthermore, site-directed mutagenesis confirms that the hQTRT1 subunit is responsible for the transglycosylase activity. Taken together, these results indicate that the human TGT is composed of a catalytic subunit, hQTRT1, and hQTRTD1, not USP14. hQTRTD1 has been implicated as the salvage enzyme that generates free queuine from QMP. Work is ongoing in our laboratory to confirm this activity. PMID- 20354155 TI - The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. AB - The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT after cold acclimatization have a mixed morphology (paucilocular adipocytes). These cells also had a mixed mitochondrioma with classic "brown" and "white" mitochondria, suggesting intermediate steps in the process of direct transformation of white into brown adipocytes (transdifferentiation). Quantitative electron microscopy disclosed that cold exposure (6 degrees C for 10 days) did not induce an increase in WAT preadipocytes. beta(3)-adrenoceptor-knockout mice had a blunted brown adipocyte occurrence upon cold acclimatization. Administration of the beta(3)-adrenoceptor agonist CL316,243 induced the occurrence of brown adipocytes, with the typical morphological features found after cold acclimatization. In contrast, administration of the beta(1)-adrenoceptor agonist xamoterol increased only the number of preadipocytes. These findings indicate that transdifferentiation depends on beta(3)-adrenoceptor activation, whereas preadipocyte recruitment is mediated by beta(1)-adrenoceptor. RT-qPCR experiments disclosed that cold exposure induced enhanced expression of the thermogenic genes and of genes expressed selectively in brown adipose tissue (iBAT) and in both interscapular BAT and WAT. beta(3)-adrenoceptor suppression blunted their expression only in WAT. Furthermore, cold acclimatization induced an increased WAT expression of the gene coding for C/EBPalpha (an antimitotic protein), whereas Ccna1 expression (related to cell proliferation) was unchanged. Overall, our data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects beta(3)-adrenoceptor-mediated transdifferentiation. PMID- 20354156 TI - LKB1 deletion with the RIP2.Cre transgene modifies pancreatic beta-cell morphology and enhances insulin secretion in vivo. AB - The tumor suppressor liver kinase B1 (LKB1), also called STK11, is a protein kinase mutated in Peutz-Jeghers syndrome. LKB1 phosphorylates AMP-activated protein kinase (AMPK) and several related protein kinases. Whereas deletion of both catalytic isoforms of AMPK from the pancreatic beta-cell and hypothalamic neurons using the rat insulin promoter (RIP2).Cre transgene (betaAMPKdKO) diminishes insulin secretion in vivo, deletion of LKB1 in the beta-cell with an inducible Pdx-1.CreER transgene enhances insulin secretion in mice. To determine whether the differences between these models reflect genuinely distinct roles for the two kinases in the beta-cell or simply differences in the timing and site(s) of deletion, we have therefore created mice deleted for LKB1 with the RIP2.Cre transgene. In marked contrast to betaAMPKdKO mice, betaLKB1KO mice showed diminished food intake and weight gain, enhanced insulin secretion, unchanged insulin sensitivity, and improved glucose tolerance. In line with the phenotype of Pdx1-CreER mice, total beta-cell mass and the size of individual islets and beta-cells were increased and islet architecture was markedly altered in betaLKB1KO islets. Signaling by mammalian target of rapamycin (mTOR) to eIF4 binding protein-1 and ribosomal S6 kinase was also enhanced. In contrast to Pdx1 CreER-mediated deletion, the expression of Glut2, glucose-induced changes in membrane potential and intracellular Ca(2+) were sharply reduced in betaLKB1KO mouse islets and the stimulation of insulin secretion was modestly inhibited. We conclude that LKB1 and AMPK play distinct roles in the control of insulin secretion and that the timing of LKB1 deletion, and/or its loss from extrapancreatic sites, influences the final impact on beta-cell function. PMID- 20354157 TI - Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouse. AB - Iron overload can cause insulin deficiency, but in some cases this may be insufficient to result in diabetes. We hypothesized that the protective effects of decreased iron would be more significant with increased beta-cell demand and stress. Therefore, we treated the ob/ob mouse model of type 2 diabetes with an iron-restricted diet (35 mg/kg iron) or with an oral iron chelator. Control mice were fed normal chow containing 500 mg/kg iron. Neither treatment resulted in iron deficiency or anemia. The low-iron diet significantly ameliorated diabetes in the mice. The effect was long lasting and reversible. Ob/ob mice on the low iron diet exhibited significant increases in insulin sensitivity and beta-cell function, consistent with the phenotype in mouse models of hereditary iron overload. The effects were not accounted for by changes in weight or feeding behavior. Treatment with iron chelation had a more dramatic effect, allowing the ob/ob mice to maintain normal glucose tolerance for at least 10.5 wk despite no effect on weight. Although dietary iron restriction preserved beta-cell function in ob/ob mice fed a high-fat diet, the effects on overall glucose levels were less apparent due to a loss of the beneficial effects of iron on insulin sensitivity. Beneficial effects of iron restriction were minimal in wild-type mice on normal chow but were apparent in mice on high-fat diets. We conclude that, even at "normal" levels, iron exerts detrimental effects on beta-cell function that are reversible with dietary restriction or pharmacotherapy. PMID- 20354158 TI - Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids. AB - Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1 7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P < 0.05). By comparison, neither mixed saturated fatty acid (100, 250, or 500 microM for 15 microg/mL, but results of blood cultures remained positive. On day 10, therapy was switched to daptomycin 6 mg/kg/day, but culture results remained positive. On day 13, testing for vancomycin heteroresistance was negative, with the MIC unchanged. The vancomycin MIC remained unchanged on day 19, but the daptomycin MIC had increased to 2 microg/mL. Rifampin 300 mg orally twice daily was added on day 20; blood cultures obtained 2 days later were sterile. The patient was discharged to complete a 6-week course of antibiotics and was doing well 4 months following therapy. DISCUSSION: Analysis of MRSA isolates obtained on days 1 and 19 showed an increase in the daptomycin MIC from 0.25 to 2 microg/mL. Because intervening isolates were not available for susceptibility testing, it is not possible to associate this increase with exposure to either vancomycin or daptomycin. Although in vitro synergy was not seen in this case, addition of rifampin to daptomycin therapy resolved the bacteremia. CONCLUSIONS: In patients with persistent MRSA bacteremia, isolates should be retested for susceptibility to both daptomycin and vancomycin, including assessment for vancomycin heteroresistance. Addition of rifampin to daptomycin may be effective for persistent MRSA bacteremia, even if daptomycin MICs are elevated. Prospective studies are needed to define the role of combination therapy. PMID- 20354161 TI - The relationship between inpatient fluoroquinolone use and Clostridium difficile associated diarrhea. AB - BACKGROUND: Limited evidence suggests there may be a link between fluoroquinolone use and Clostridium difficile-associated diarrhea (CDAD), but such an association remains unclear due to conflicting data. OBJECTIVE: To determine the relationship between inpatient fluoroquinolone use and CDAD; secondary objectives included the relationship between CDAD and fluoroquinolone selection, duration of therapy, and route of administration, as well as the association between fluoroquinolones and CDAD complications. METHODS: We conducted a retrospective, case-control study of adult inpatients diagnosed with CDAD during the period of July 2007-July 2008. In total, 174 case patients were matched on a 1:1 basis with controls. A thorough assessment of all inpatient antibiotic use was conducted, including regimens administered at our institution within the previous 8 weeks. Odds ratios were calculated using univariate logistic-regression analysis. RESULTS: Use of fluoroquinolones was not significantly different between patients with CDAD and matching controls (OR 1.36; 95% CI 0.09 to 2.10; p = 0.16). No relationship was found between CDAD and the individual fluoroquinolones: ciprofloxacin (OR 1.36; 95% CI 0.87 to 2.12; p = 0.18), levofloxacin (OR 1.17; 95% CI 0.62 to 2.22; p = 0.63), and moxifloxacin (OR 1.34; 95% CI 0.81 to 2.20; p = 0.25). Fluoroquinolone route of administration did not differ significantly between groups for patients receiving intravenous (OR 1.20; 95% CI 0.74 to 1.94; p = 0.46) or oral (OR 0.79; 95% CI 0.44 to 1.44; p = 0.45) therapy. Complications from CDAD were not significantly increased by fluoroquinolone use (OR 1.37; 95% CI 0.72 to 2.61; p = 0.35). CONCLUSIONS: Inpatient administration of fluoroquinolones was not associated with CDAD at our institution. Fluoroquinolone use in patients who developed CDAD was not related to higher incidences of CDAD-related complications. PMID- 20354162 TI - Fiberoptic resonance Raman spectroscopy to measure carotenoid oxidative breakdown in live tissues. AB - Based on compelling epidemiologic and corroboratory in vitro studies, carotenoids are thought to have great potential as dietary prevention against cancer. Yet, carotenoid-based chemopreventive trials have found very contradictory results. Definitive conclusions from these trials are hampered by an inability to accurately and safely measure carotenoids in specific tissues at risk of cancer development. Raman spectroscopy has been proposed as an optical technology with which to analyze various molecules in live tissues. One major obstacle that impedes the clinical use of this powerful technology is the lack of a fiberoptic Raman probe suitable for endoscopic tissue evaluation. A single-fiber resonance Raman Spectroscope capable of noninvasive "optical biopsies" to measure carotenoid concentrations in live tissues has been developed. The accuracy of this Raman instrument was confirmed by comparison with more standard methods of spectrophotometry and high-pressure liquid chromatography using solubilized beta carotene (BC) and BC-loaded cells before use in a small patient cohort. This Raman instrument detected intact BC as well as BC oxidative breakdown as a decrement of its Raman signal in cells. Use of the Raman instrument in our small cohort study showed its feasibility for measuring human tissues and raised some potentially intriguing possibilities about BC tissue pharmacokinetics and oxidative biology. Based on these results, our newly developed single fiberoptic resonance Raman instrument may provide a very useful method of measuring carotenoids and their oxidative breakdown within live tissue during future carotenoid chemopreventive trials. This proof-of-concept study provides the foundation to justify future validation of our Raman prototype. PMID- 20354163 TI - Unprecedented opportunities and promise for cancer prevention research. AB - Cancer prevention encompasses a wide range of highly developed science and clinical impact. Enunciating these two aspects in the same breath highlights the crucial link between them. The breadth and excitement of current opportunities in the science of cancer prevention have never been greater. Major avenues of such research include the extent and effect of premalignancy, the molecular underpinnings of carcinogenesis and related prevention targets, in vitro model systems of the progression of normal human epithelial cells to tumorigenesis, molecular risk stratification and pharmacogenomic approaches, and many more. We describe the clinical impacts of cancer prevention (with examples in the areas of molecular targeting, vaccines, epidemiology, and behavioral science) and the stage-setting science that facilitated them. In addition, discussed are new prevention opportunities such as interactions between stromal and microenvironmental factors, the control of premalignant stem cell phenotypes through epigenetic reprogramming, and neoplastic cells and various stress responses including those involving telomere biology. The promise of this science, particularly integrative, interdisciplinary research, is to hasten the ability of clinical prevention to reduce the burden of cancer. PMID- 20354164 TI - Knockout of the tumor suppressor gene Gprc5a in mice leads to NF-kappaB activation in airway epithelium and promotes lung inflammation and tumorigenesis. AB - Mouse models can be useful for increasing the understanding of lung tumorigenesis and assessing the potential of chemopreventive agents. We explored the role of inflammation in lung tumor development in mice with knockout of the tumor suppressor Gprc5a. Examination of normal lung tissue and tumors from 51 Gprc5a(+/+) (adenoma incidence, 9.8%; adenocarcinoma, 0%) and 38 Gprc5a(-/-) mice (adenoma, 63%; adenocarcinoma, 21%) revealed macrophage infiltration into lungs of 45% of the Gprc5a(-/-) mice and 8% of Gprc5a(+/+) mice and the direct association of macrophages with 42% of adenomas and 88% of adenocarcinomas in the knockout mice. Gprc5a(-/-) mouse lungs contained higher constitutive levels of proinflammatory cytokines and chemokines and were more sensitive than lungs of Gprc5a(+/+) mice to stimulation of NF-kappaB activation by lipopolysaccharide in vivo. Studies with epithelial cells cultured from tracheas of Gprc5a(-/-) and Gprc5a(+/+) mice revealed that Gprc5a loss is associated with increased cell proliferation, resistance to cell death in suspension, and increased basal, tumor necrosis factor alpha-induced, and lipopolysaccharide-induced NF-kappaB activation, which were reversed partially in Gprc5a(-/-) adenocarcinoma cells by reexpression of Gprc5a. Compared with Gprc5a(+/+) cells, the Gprc5a(-/-) cells produced higher levels of chemokines and cytokines and their conditioned medium induced more extensive macrophage migration. Silencing Gprc5a and the p65 subunit of NF-kappaB in Gprc5a(+/+) and Gprc5a(-/-) cells, respectively, reversed these effects. Thus, Gprc5a loss enhances NF-kappaB activation in lung epithelial cells, leading to increased autocrine and paracrine interactions, cell autonomy, and enhanced inflammation, which may synergize in the creation of a tumor promoting microenvironment. PMID- 20354165 TI - Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer. AB - We evaluated the association between energy balance and risk of bladder cancer and assessed the joint effects of genetic variants in the mammalian target of rapamycin (mTOR) pathway genes with energy balance. The study included 803 Caucasian bladder cancer patients and 803 healthy Caucasian controls matched to cases by age (+/-5 years) and gender. High energy intake [odds ratio, 1.60; 95% confidence interval (95% CI), 1.23-2.09] and low physical activity (odds ratio, 2.82; 95% CI, 2.10-3.79) were each associated with significantly increased risk of bladder cancer with dose-response pattern (P(trend) < 0.001). However, obesity (body mass index, > or =30) was not associated with the risk. Among 222 single nucleotide polymorphisms, 28 single nucleotide polymorphisms located in six genes of mTOR pathway were significantly associated with the risk. Further, the risk associated with high energy intake and low physical activity was only observed among subjects carrying a high number of unfavorable genotypes in the pathway. Moreover, when physical activity, energy intake, and genetic variants were analyzed jointly, the study population was clearly stratified into a range of low to high-risk subgroups as defined energy balance status. Compared with subjects within the most favorable energy balance category (low energy intake, intensive physical activity, low number of unfavorable genotypes), subjects in the worst energy balance category (high energy intake, low physical activity, and carrying > or =7 unfavorable genotypes) had 21.93-fold increased risk (95% CI, 6.7-71.77). Our results provide the first strong evidence that physical activity, energy intake, and genetic variants in the mTOR pathway jointly influence bladder cancer susceptibility and that these results have implications for bladder cancer prevention. PMID- 20354166 TI - NF-kappaB fans the flames of lung carcinogenesis. AB - This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-kappaB and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-kappaB activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-kappaB downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. PMID- 20354167 TI - Highlighting the science of cancer prevention. PMID- 20354168 TI - AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species. AB - Although AKT is essential for multiple cellular functions, the role of this kinase family in hematopoietic stem cells (HSCs) is unknown. Thus, we analyzed HSC function in mice deficient in the 2 isoforms most highly expressed in the hematopoietic compartment, AKT1 and AKT2. Although loss of either isoform had only a minimal effect on HSC function, AKT1/2 double-deficient HSCs competed poorly against wild-type cells in the development of myeloid and lymphoid cells in in vivo reconstitution assays. Serial transplantations revealed an essential role for AKT1 and AKT2 in the maintenance of long-term HSCs (LT-HSCs). AKT1/2 double-deficient LT-HSCs were found to persist in the G(0) phase of the cell cycle, suggesting that the long-term functional defects are caused by increased quiescence. Furthermore, we found that the intracellular content of reactive oxygen species (ROS) is dependent on AKT because double-deficient HSCs demonstrate decreased ROS. The importance of maintaining ROS for HSC differentiation was shown by a rescue of the differentiation defect after pharmacologically increasing ROS levels in double-deficient HSCs. These data implicate AKT1 and AKT2 as critical regulators of LT-HSC function and suggest that defective ROS homeostasis may contribute to failed hematopoiesis. PMID- 20354169 TI - The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function. AB - The von Willebrand factor (VWF) A2 crystal structure has revealed the presence of a rare vicinal disulfide bond between C1669 and C1670, predicted to influence domain unfolding required for proteolysis by ADAMTS13. We prepared VWF A2 domain fragments with (A2-VicCC, residues 1473-1670) and without the vicinal disulfide bond (A2-DeltaCC, residues 1473-1668). Compared with A2-DeltaCC, A2-VicCC exhibited impaired proteolysis and also reduced binding to ADAMTS13. Circular dichroism studies revealed that A2-VicCC was more resistant to thermal unfolding than A2-DeltaCC. Mutagenesis of C1669/C1670 in full-length VWF resulted in markedly increased susceptibility to cleavage by ADAMTS13, confirming the important role of the paired vicinal cysteines in VWF A2 domain stabilization. PMID- 20354170 TI - Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. AB - Vascular calcification is a marker of increased cardiovascular risk. Vitamin K dependent matrix Gla protein (MGP) is important in inhibiting calcification. Because MGP activation is vitamin K dependent, we performed a cross-sectional study investigating the relationship between the use of vitamin K antagonists and extracoronary vascular calcification. From the Dutch thrombosis services we selected 19 patients younger than 55 years who had no other cardiovascular risk factors and who had used coumarins for more than 10 years, and compared these to 18 matched healthy controls. MGP was measured, and a plain x-ray of the thighs was taken to assess femoral arterial calcifications. The odds ratio for calcification in patients versus controls was 8.5 (95% confidence interval [CI] 2.01-35.95). Coumarin use and MGP were associated with calcification, even after adjusting for other risk factors. We conclude that long-term use of coumarins is associated with enhanced extracoronary vascular calcification, possibly through the inhibition of MGP carboxylation. PMID- 20354171 TI - Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. AB - Disrupted hematopoiesis and delayed immune reconstitution are life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although graft-versus-host disease (GVHD) is a major risk factor for the bone marrow (BM) insufficiency, how GVHD impairs BM hematopoiesis has been largely unknown. We hypothesized that BM stromal niche could be a target of GVHD. In major histocompatibility complex (MHC)-mismatched murine models of GVHD, we have demonstrated the early destruction of osteoblasts that especially affected B-cell lineages. The defective B lymphopoiesis was due to the impaired ability of BM stroma and osteoblasts to support the hematopoiesis, as evidenced by the failure of GVHD-affected BM to reconstitute the hematopoietic cells. The administration of anti-CD4 monoclonal antibody (mAb) ameliorated these effects and improved B lymphopoiesis while preserving graft-versus-tumor effects. Genetic ablation of Fas-Fas ligand signaling also partially restored B lymphopoiesis. Our present study provided evidence of BM GVHD, with the identification of osteoblasts as the main target for GVHD in BM. Moreover, our data showed the potential for mAb therapies to enhance immune reconstitution in vivo for patients undergoing allo HSCT. PMID- 20354172 TI - BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia. AB - Resistance to glucocorticoids (GCs) is a major clinical problem in the treatment of acute lymphoblastic leukemia (ALL), but the underlying mechanisms are not well understood. Although mutations in the glucocorticoid receptor (GR) gene can give rise to therapy resistance in vitro, acquired somatic mutations in the GR are rarely encountered in patients. Here we report that the protein encoded by the BTG1 gene, which is frequently deleted in (pediatric) ALL, is a key determinant of GC responsiveness. Using RNA interference, we show that loss of BTG1 expression causes GC resistance both by decimating GR expression and by controlling GR-mediated transcription. Conversely, reexpression of BTG1 restores GC sensitivity by potentiating GC-induced GR expression, a phenomenon known as GR autoinduction. In addition, the arginine methyltransferase PRMT1, a BTG1-binding partner and transcriptional coactivator, is recruited to the GR gene promoter in a BTG1-dependent manner. These results implicate the BTG1/PRMT1 complex in GR mediated gene expression and reveal that deregulation of a nuclear receptor coactivator complex can give rise to GC resistance. Further characterization of this complex as part of the GR regulatory circuitry could offer novel opportunities for improving the efficacy of GC-based therapies in ALL and other hematologic malignancies. PMID- 20354173 TI - Toll-like receptor-induced reactivity and strongly potentiated IL-8 production in granulocytes mobilized for transfusion purposes. AB - Transfusion of granulocytes from granulocyte-colony stimulating factor (G CSF)/dexamethasone (dexa)-treated donors can be beneficial for neutropenic recipients that are refractory to antimicrobial therapy. G-CSF/dexa treatment not only increases the number of circulating neutrophils but also affects their gene expression. Because of the intended transfusion of these granulocytes into patients who are severely ill, it is of importance to establish to what extent mobilization affects the cellular behavior of neutrophils. Here, we studied the effects of mobilization on Toll-like receptor (TLR)-mediated responses. Mobilized granulocytes displayed increased gene and protein expression of TLR2, TLR4, TLR5, and TLR8. Although mobilized granulocytes displayed normal priming of nicotinamide adenine dinucleotide phosphate oxidase activity and a slight increase in adhesion in response to TLR stimulation, these cells produced massive amounts of interleukin-8 (IL-8), in particular to TLR2 and TLR8 stimulation. The increase in IL-8 release occurred despite reduced IL-8 mRNA levels in the donor granulocytes after in vivo G-CSF/dexa treatment, indicating that the enhanced TLR induced IL-8 production was largely determined by posttranscriptional regulation. In summary, granulocytes mobilized for transfusion purposes show enhanced TLR responsiveness in cytokine production, which is anticipated to be beneficial for the function of these cells on transfusion into patients. PMID- 20354175 TI - A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes. AB - Leukocytes rely on dynamic actin-dependent changes in cell shape to pass through blood vessels, which is fundamental to immune surveillance. Wiskott-Aldrich Syndrome protein (WASp) is a hematopoietic cell-restricted cytoskeletal regulator important for modulating cell shape through Arp2/3-mediated actin polymerization. A recently identified WASp(I294T) mutation was shown to render WASp constitutively active in vivo, causing increased filamentous (F)-actin polymerization, high podosome turnover in macrophages, and myelodysplasia. The aim of this study was to determine the effect of WASp(I294T) expression in lymphocytes. Here, we report that lymphocytes isolated from a patient with WASp(I294T), and in a cellular model of WASp(I294T), displayed abnormal microvillar architecture, associated with an increase in total cellular F-actin. Microvillus function was additionally altered as lymphocytes bearing the WASp(I294T) mutation failed to roll normally on L-selectin ligand under flow. This was not because of defects in L-selectin expression, shedding, cytoskeletal anchorage, or membranal positioning; however, under static conditions of adhesion, WASp(I294T)-expressing lymphocytes exhibited altered dynamic interaction with L-selectin ligand, with a significantly reduced rate of adhesion turnover. Together, our results demonstrate that WASp(I294T) significantly affects lymphocyte membrane topography and L-selectin-dependent adhesion, which may be linked to defective hematopoiesis and leukocyte function in affected patients. PMID- 20354174 TI - Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration. AB - Cocaine abuse hastens the neurodegeneration often associated with advanced HIV-1 infection. The mechanisms, in part, revolve around the neuroinflammatory processes mediated by the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2). Understanding factors that modulate MCP-1 and, in turn, facilitate monocyte extravasation in the brain is thus of paramount importance. We now demonstrate that cocaine induces MCP-1 in rodent microglia through translocation of the sigma receptor to the lipid raft microdomains of the plasma membrane. Sequential activation of Src, mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3' kinase (PI3K)/Akt and nuclear factor kappaB (NF-kappaB) pathways resulted in increased MCP-1 expression. Furthermore, conditioned media from cocaine-exposed microglia increased monocyte transmigration, and thus was blocked by antagonists for CCR2 or sigma receptor. These findings were corroborated by demonstrating increased monocyte transmigration in mice exposed to cocaine, which was attenuated by pretreatment of mice with the sigma receptor antagonist. Interestingly, cocaine-mediated transmigratory effects were not observed in CCR2 knockout mice. We conclude that cocaine-mediated induction of MCP-1 accelerates monocyte extravasation across the endothelium. Understanding the regulation of MCP-1 expression and functional changes by cocaine/sigma receptor system may provide insights into the development of potential therapeutic targets for HIV-1-associated neurocognitive disorders. PMID- 20354176 TI - Pharmacodynamic and pharmacokinetic characterization of the aldosterone synthase inhibitor FAD286 in two rodent models of hyperaldosteronism: comparison with the 11beta-hydroxylase inhibitor metyrapone. AB - Aldosterone synthase (CYP11B2) inhibitors (ASIs) represent an attractive therapeutic approach for mitigating the untoward effects of aldosterone. We characterized the pharmacokinetic/pharmacodynamic relationships of a prototypical ASI, (+)-(5R)-4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl]benzonitrile hydrochloride (CGS020286A, FAD286, FAD) and compared these profiles to those of the 11beta-hydroxylase inhibitor metyrapone (MET) in two rodent models of secondary hyperaldosteronism and corticosteronism. In chronically cannulated Sprague-Dawley rats, angiotensin II (ANG II) (300 ng/kg bolus + 100 ng/kg/min infusion) or adrenocorticotropin (100 ng/kg + 30 ng/kg/min) acutely elevated plasma aldosterone concentration (PAC) from approximately 0.26 nM to a sustained level of approximately 2.5 nM for 9 h. Adrenocorticotropin but not ANG II elicited a sustained increase in plasma corticosterone concentration (PCC) from approximately 300 to approximately 1340 nM. After 1 h of Ang II or adrenocorticotropin infusion, FAD (0.01-100 mg/kg p.o.) or MET (0.1-300 mg/kg p.o.) dose- and drug plasma concentration-dependently reduced the elevated PACs over the ensuing 8 h. FAD was approximately 12 times more dose-potent than MET in reducing PAC but of similar or slightly greater potency on a plasma drug concentration basis. Both agents also decreased PCC in the adrenocorticotropin model at relatively higher doses and with similar dose potencies, whereas FAD was 6-fold weaker based on drug exposures. FAD was approximately 50-fold selective for reducing PAC versus PCC, whereas MET was only approximately 3-fold selective. We conclude that FAD is a potent, orally active, and relatively selective ASI in two rat models of hyperaldosteronism. MET is an order of magnitude less selective than FAD but is, nevertheless, more potent as an ASI than as an 11beta hydroxylase inhibitor. PMID- 20354177 TI - Neuropeptide FF receptors have opposing modulatory effects on nociception. AB - The role of neuropeptide FF (NPFF) and its analogs in pain modulation is ambiguous. Although NPFF was first characterized as an antiopioid peptide, both antinociceptive and pronociceptive effects have been reported, depending on the route of administration. Currently, two NPFF receptors, termed FF1 and FF2, have been identified and cloned, but their roles in pain modulation remain elusive because of the lack of availability of selective compounds suitable for systemic administration in in vivo models. Ligand-binding studies confirm ubiquitous expression of both subtypes in brain, whereas only FF2 receptors are expressed spinally. This disparity in localization has served as the foundation of the hypothesis that FF1 receptors mediate the pronociceptive actions of NPFF. We have identified novel small molecule NPFF receptor agonists and antagonists with varying degrees of FF2/FF1 functional selectivity. Using these pharmacological tools in vivo has allowed us to define the roles of NPFF receptor subtypes as pertains to the modulation of nociception. We demonstrate that selective FF2 agonism does not modulate acute pain but instead ameliorates inflammatory and neuropathic pains. Treatment with a nonselective FF1/FF2 agonist potentiates allodynia in neuropathic rats and increases sensitivity to noxious thermal and to non-noxious mechanical stimuli in normal rats in an FF1 antagonist-reversible manner. Treatment with FF1 antagonists reversed established mechanical allodynia, indicating the possibility of increased NPFF tone through FF1 receptors. In conclusion, we provide evidence for the opposing roles of NPFF receptors and highlight selective FF2 agonism and/or selective FF1 antagonism as potential targets warranting further investigation. PMID- 20354178 TI - The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling. AB - Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. PMID- 20354179 TI - Genetic screen identifies insulin-like growth factor binding protein 5 as a modulator of tamoxifen resistance in breast cancer. AB - Tamoxifen resistance is one of the overarching challenges in the treatment of patients with estrogen receptor (ER)-positive breast cancer. Through a genome wide RNA interference screen to discover genes responsible for tamoxifen resistance in vitro, we identified insulin-like growth factor binding protein 5 (IGFBP5) as a determinant of drug sensitivity. Specific knockdown of IGFBP5 by retroviral infection with short hairpin RNA-expressing cassette in MCF7 human breast cancer cells (pRS-shIGFBP5) conferred tamoxifen resistance in vitro due to concomitant loss of ERalpha expression and signaling. IGFBP5 expression was also reduced in MCF7 cells selected for tamoxifen resistance in culture (TAMR). Both tamoxifen-resistant MCF7-TAMR and MCF7-pRS-shIGFBP5 cells could be resensitized to drug by treatment with exogenous recombinant IGFBP5 (rIGFBP5) protein. Treatment with rIGFBP5 protein in mouse tumor xenografts reversed the in vivo tamoxifen resistance of MCF7-pRS-shIGFBP5 cell-derived tumors by reducing tumor cell proliferation. IGFBP5 immunohistochemical staining in a cohort of 153 breast cancer patients showed that low IGFBP5 expression was associated with shorter overall survival after tamoxifen therapy. Thus, IGFBP5 warrants investigation as an agent to reverse tamoxifen resistance. PMID- 20354180 TI - Cancer stem cells promote tumor vascular development--letter. PMID- 20354182 TI - In vivo cytotoxicity of type I CD20 antibodies critically depends on Fc receptor ITAM signaling. AB - Antibody-Fc receptor (FcR) interactions play an important role in the mechanism of action of most therapeutic antibodies against cancer. Effector cell activation through FcR triggering may induce tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC). Reciprocally, FcR cross-linking of antibody may lead to the induction of apoptotic signaling in tumor cells. The relative importance of these bisecting pathways to in vivo antibody activity is unknown. To unravel these roles, we developed a novel mouse model with normal FcR expression but in which FcR signaling was inactivated by mutation of the associated gamma-chain. Transgenic mice showed similar immune complex binding compared with wild-type mice. In contrast, ADCC of cells expressing frequently used cancer targets, such as CD20, epidermal growth factor receptor, Her2, and gp75, was abrogated. Using the therapeutic CD20 antibodies ofatumumab and rituximab, we show that FcR cross-linking of antibody-antigen immune complexes in the absence of gamma-chain signaling is insufficient for their therapeutic activity in vivo. ADCC therefore represents an essential mechanism of action for immunotherapy of lymphoid tumors. PMID- 20354184 TI - A therapeutic anti-VEGF antibody with increased potency independent of pharmacokinetic half-life. AB - Bevacizumab [Avastin; anti-vascular endothelial growth factor (VEGF) antibody] is an antiangiogenic IgG approved for treating patients with certain types of colon, breast, and lung cancer. In these indications, bevacizumab is administered every 2 to 3 weeks, prompting us to study ways to reduce the frequency of administration. Increasing affinity to neonatal Fc receptor (FcRn) may extend the pharmacokinetic half-life of an antibody, but the quantitative effect of FcRn affinity on clearance has not been clearly elucidated. To gain further insight into this relationship, we engineered a series of anti-VEGF antibody variants with minimal amino acid substitutions and showed a range of half-life improvements in primates. These results suggest that, if proven clinically safe and effective, a modified version of bevacizumab could potentially provide clinical benefit to patients on long-term anti-VEGF therapy through less-frequent dosing and improved compliance with drug therapy. Moreover, despite having half life similar to that of wild-type in mice due to the species-specific FcRn binding effects, the variant T307Q/N434A exhibited superior in vivo potency in slowing the growth of certain human tumor lines in mouse xenograft models. These results further suggest that FcRn variants may achieve increased potency through unidentified mechanisms in addition to increased systemic exposure. PMID- 20354183 TI - Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer. AB - Aromatase inhibitors play a prominent role in the management of postmenopausal women with endocrine-sensitive breast cancer, but there is large variability in both efficacy and tolerability. The purpose of our study was to define interindividual variation in anastrozole metabolism and pharmacodynamics among patients treated with the approved daily dose of 1 mg in a standard practice setting as adjuvant therapy for resected early breast cancer. This study was performed in 191 women in whom pretreatment and during anastrozole plasma concentrations of estrone (E1), estradiol (E2), estrone conjugates, androstenedione, and testosterone were determined and correlated with plasma concentrations of anastrozole and anastrozole metabolites. There were large interindividual variations in plasma anastrozole and anastrozole metabolite concentrations, as well as pretreatment and postdrug plasma E1, E2, and E1 conjugate and estrogen precursor (androstenedione and testosterone) concentrations. E1 and E2 concentrations were below the lower limit of quantitation (LLQ) in most patients after anastrozole therapy (83% for both), but those with detectable concentrations had a broad range (1.58-45.2 and 0.635-97.0 pg/mL, respectively). E1 conjugates after anastrozole therapy were above the LLQ in most patients (93%), with wide interpatient variability (3.50-2,990 pg/mL). Two patients seemed to extensively metabolize anastrozole and failed to display substantial decreases in estrogens. Acknowledging the potential factor of variable compliance, our results showed large interindividual variation in anastrozole metabolism and its effect on circulating estrogens in postmenopausal patients. These findings may have implications with regard to efficacy and adverse events and may indicate the need to "individualize" therapy with this drug. PMID- 20354185 TI - Induction of cancer cell death by self-assembling nanostructures incorporating a cytotoxic peptide. AB - Nanotechnology offers novel delivery vehicles for cancer therapeutics. Potential advantages of nanoscale platforms include improved pharmacokinetics, encapsulation of cytotoxic agents, enhanced accumulation of therapeutics in the tumor microenvironment, and improved therapeutic structures and bioactivity. Here, we report the design of a novel amphiphilic molecule that self-assembles into nanostructures for intracellular delivery of cytotoxic peptides. Specifically, a cationic alpha-helical (KLAKLAK)(2) peptide that is known to induce cancer cell death by membrane disruption was integrated into a peptide amphiphile (PA) that self-assembles into bioactive, cylindrical nanofibers. PAs are composed of a hydrophobic alkyl tail, a beta-sheet forming peptide, and a bioactive peptide that is displayed on the surface of the nanofiber after self assembly. PA nanostructures that included (KLAKLAK)(2) were readily internalized by breast cancer cells, in contrast to the (KLAKLAK)(2) peptide that on its own was not cell permeable. (KLAKLAK)(2) nanostructures, but not the peptides alone, also induced breast cancer cell death by caspase-independent and Bax/Bak independent mechanisms associated with membrane disruption. Significantly, (KLAKLAK)(2) nanostructures induced cell death more robustly in transformed breast epithelial cells than in untransformed cells, suggesting a degree of tumor selectivity. Our results provide proof-of-principle that self-assembling PAs can be rationally designed to generate nanostructures that can efficiently deliver cytotoxic peptides to cancer cells. PMID- 20354186 TI - p66Shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells. AB - Naturally occurring phenethyl isothiocyanate (PEITC) selectively inhibits growth of cancer cells by causing apoptosis, but the mechanism of cell death induction is not fully understood. We now show, for the first time, that growth factor adapter protein p66(Shc) is indispensable for PEITC-induced apoptosis. Mouse embryonic fibroblasts derived from p66(Shc) knockout mice were significantly more resistant to PEITC-mediated growth inhibition, cytoplasmic histone-associated apoptotic DNA fragmentation, and caspase-3 activation compared with wild-type fibroblasts. The PEITC treatment resulted in induction as well as increased Ser(36) phosphorylation of p66(Shc) in PC-3 and LNCaP human prostate cancer cells. Knockdown of p66(Shc) protein conferred significant protection against PEITC-mediated cytoplasmic histone-associated DNA fragmentation as well as production of reactive oxygen species in both PC-3 and LNCaP cells. The PEITC treated PC-3 and LNCaP cells exhibited increased binding of p66(Shc) with prolyl isomerase Pin1, a protein implicated in translocation of p66(Shc) to mitochondria. Consistent with these results, treatment of PC-3 cells with PEITC resulted in translocation of p66(Shc) to the mitochondria as judged by immunoblotting using cytosolic and mitochondrial fractions and immunofluorescence microscopy. Growth suppression and apoptosis induction in tumor xenografts in vivo by oral administration of PEITC to the PC-3 tumor-bearing male athymic mice were accompanied by statistically significant increase in the level of Ser(36) phosphorylated p66(Shc). Collectively, these results provide novel insight into the critical role of p66(Shc) in regulation of PEITC-induced apoptotic cell death in human prostate cancer cells. PMID- 20354187 TI - The c-Jun NH2-terminal kinase 2 plays a dominant role in human epidermal neoplasia. AB - The c-Jun NH(2)-terminal kinase (JNK) signaling cascade has been implicated in a wide range of diseases, including cancer. It is unclear how different JNK proteins contribute to human cancer. Here, we report that JNK2 is activated in more than 70% of human squamous cell carcinoma (SCC) samples and that inhibition of JNK2 pharmacologically or genetically impairs tumorigenesis of human SCC cells. Most importantly, JNK2, but not JNK1, is sufficient to couple with oncogenic Ras to transform primary human epidermal cells into malignancy with features of SCC. JNK2 prevents Ras-induced cell senescence and growth arrest by reducing the expression levels of the cell cycle inhibitor p16 and the activation of NF-kappaB. On the other hand, JNK, along with phosphoinositide 3-kinase, is essential for Ras-induced glycolysis, an energy-producing process known to benefit cancer growth. These data indicate that JNK2 collaborates with other oncogenes, such as Ras, at multiple molecular levels to promote tumorigenesis and hence represents a promising therapeutic target for cancer. PMID- 20354188 TI - MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. AB - MicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the mechanisms by which miR-155 functions as a putative oncomiR are largely unknown. Here, we report that the tumor suppressor gene suppressor of cytokine signaling 1 (socs1) is an evolutionarily conserved target of miR-155 in breast cancer cells. We found that mir-155 expression is inversely correlated with socs1 expression in breast cancer cell lines as well as in a subset of primary breast tumors. We also identified a 24A-->G mutation in the miR-155 binding site of the SOCS1 3' untranslated region in a breast tumor that reduced miR-155 repression, implicating a mechanism for miRNA targets to avoid repression. Ectopic expression of miR-155 significantly promoted the proliferation of breast cancer cells, the formation of soft agar foci in vitro, and the development of tumors in nude mice. In breast cancer cells, RNA interference silencing of socs1 recapitulates the oncogenic effects of miR-155, whereas restoration of socs1 expression attenuates the protumorigenesis function of miR-155, suggesting that miR-155 exerts its oncogenic role by negatively regulating socs1. Overexpression of miR-155 in breast cancer cells leads to constitutive activation of signal transducer and activator of transcription 3 (STAT3) through the Janus-activated kinase (JAK) pathway, and stimulation of breast cancer cells by the inflammatory cytokines IFN gamma and interleukin-6 (IL-6), lipopolysaccharide (LPS), and polyriboinosinic:polyribocytidylic acid [poly(I:C)] significantly upregulates mir 155 expression, suggesting that miR-155 may serve as a bridge between inflammation and cancer. Taken together, our study reveals that miR-155 is an oncomiR in breast cancer and that miR-155 may be a potential target in breast cancer therapy. PMID- 20354189 TI - The connectivity map links iron regulatory protein-1-mediated inhibition of hypoxia-inducible factor-2a translation to the anti-inflammatory 15-deoxy delta12,14-prostaglandin J2. AB - Hypoxia-inducible factors 1 and 2 (HIF1 and HIF2) are heterodimeric transcription factors consisting of alpha regulatory subunits and a constitutively expressed beta subunit. The expression of alpha regulatory subunits is promoted by hypoxia, cancer-associated mutations, and inflammatory cytokines. Thus, HIF1 and HIF2 provide a molecular link between cancer and inflammation. We have recently identified novel small molecules that selectively inhibit translation of the HIF2a message and thereby powerfully inhibit the expression of HIF2a target genes. We report here that Connectivity Map analysis links three of these compounds to the anti-inflammatory cytokine 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)). As with our identified compounds, PGJ(2) inhibits translation of the HIF2a message in a mammalian target of rapamycin-independent manner by promoting the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) embedded within the 5'-untranslated region of the HIF2a message. The IRE is necessary and sufficient for mediating the effect. Mutation of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ(2) on HIF2a translation. This is the first report of an endogenous natural molecule regulating HIF2a translation, and it suggests that part of the anti inflammatory and putative antineoplastic effects of PGJ(2) may be mediated through inhibition of HIF2a within tumor epithelial cells themselves and/or mesenchymal cells of the tumor microenvironment. PMID- 20354190 TI - Noscapine, a benzylisoquinoline alkaloid, sensitizes leukemic cells to chemotherapeutic agents and cytokines by modulating the NF-kappaB signaling pathway. AB - Noscapine, a benzylisoquinoline alkaloid derived from opium, was recently reported to exhibit activity against a variety of cancers through a poorly understood mechanism. Because the transcription factor NF-kappaB has been linked with inflammation, survival, proliferation, invasion, and angiogenesis in tumors, we hypothesized that noscapine mediates its effects by modulating the NF-kappaB activation pathway. We found that noscapine potentiates apoptosis induced by cytokines and chemotherapeutic agents in tumor cells. Noscapine alone suppressed proliferation of human leukemia and myeloma cells and downregulated the constitutive expression of cell survival proteins. Noscapine also abrogated the inducible expression of proteins involved in survival, proliferation, invasion, and angiogenesis, all of which are regulated by NF-kappaB. Noscapine suppressed both inducible and constitutive NF-kappaB activation in tumor cells through inhibition of IkappaB kinase, leading to inhibition of phosphorylation and degradation of IkappaBalpha. Noscapine also suppressed phosphorylation and nuclear translocation of p65, leading to inhibition of NF-kappaB reporter activity induced by various components of the NF-kappaB activation pathway. Activity of the NF-kappaB-containing cyclooxygenase-2 promoter was also inhibited by noscapine. Thus, noscapine inhibits the proliferation of leukemia cells and sensitizes them to tumor necrosis factor and chemotherapeutic agents by suppressing the NF-kappaB signaling pathway. PMID- 20354191 TI - Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. AB - Activation of cyclin-dependent kinases 4 and 6 (cdk4/6) occurs in the majority of glioblastoma multiforme (GBM) tumors, and represents a promising molecular target for the development of small molecule inhibitors. In the current study, we investigated the molecular determinants and in vivo response of diverse GBM cell lines and xenografts to PD-0332991, a cdk4/6-specific inhibitor. In vitro testing of PD-0332991 against a panel of GBM cell lines revealed a potent G(1) cell cycle arrest and induction of senescence in each of 16 retinoblastoma protein (Rb) proficient cell lines regardless of other genetic lesions, whereas 5 cell lines with homozygous inactivation of Rb were completely resistant to treatment. Short hairpin RNA depletion of Rb expression conferred resistance of GBM cells to PD 0332991, further demonstrating a requirement of Rb for sensitivity to cdk4/6 inhibition. PD-0332991 was found to efficiently cross the blood-brain barrier and proved highly effective in suppressing the growth of intracranial GBM xenograft tumors, including those that had recurred after initial therapy with temozolomide. Remarkably, no mice receiving PD-0332991 died as a result of disease progression while on therapy. Additionally, the combination of PD-0332991 and radiation therapy resulted in significantly increased survival benefit compared with either therapy alone. In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy. PMID- 20354192 TI - A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. AB - Human papillomavirus (HPV) types differ profoundly in cervical carcinogenicity. For the most carcinogenic type HPV16, variant lineages representing further evolutionary divergence also differ in cancer risk. Variants of the remaining 10 to 15 carcinogenic HPV types have not been well studied. In the first prospective, population-based study of HPV variants, we explored whether, on average, the oldest evolutionary branches within each carcinogenic type predicted different risks of >2-year viral persistence and/or precancer and cancer [cervical intraepithelial neoplasia grade 3+ (CIN3+)]. We examined the natural history of HPV variants in the 7-year, 10,049-woman Guanacaste Cohort Study, using a nested case-control design. Infections were assigned to a variant lineage determined by phylogenetic parsimony methods based on URR/E6 sequences. We used the Fisher's combination test to evaluate significance of the risk associations, cumulating evidence across types. Globally, for HPV types including HPV16, the P value was 0.01 for persistence and 0.07 for CIN3+. Excluding HPV16, the P values were 0.04 and 0.37, respectively. For HPV16, non-European viral variants were significantly more likely than European variants to cause persistence [odds ratio (OR), 2.6; P = 0.01] and CIN3+ (OR, 2.4; P = 0.004). HPV35 and HPV51 variant lineages also predicted CIN3+. HPV variants generally differ in risk of persistence. For some HPV types, especially HPV16, variant lineages differ in risk of CIN3+. The findings indicate that continued evolution of HPV types has led to even finer genetic discrimination linked to HPV natural history and cervical cancer risk. Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16's unique carcinogenicity. PMID- 20354193 TI - Seasonal nitrogen cycling in the bark of field-grown Grey poplar is correlated with meteorological factors and gene expression of bark storage proteins. AB - Seasonal tree-internal nitrogen cycling is an important strategy for trees to achieve high efficiency in the use of nitrogen (N). Key processes of this N redistribution are autumnal leaf senescence and storage of released N as bark storage proteins (BSP) in perennial tissues. While the regulation of leaf senescence has been intensively analysed in trees, the coordination of the complementary storage processes is still poorly understood. Therefore, we ascertained relationships between physiological-level and molecular-level processes and environmental factors under natural conditions in the bark of Populus x canescens. We analysed amino-N concentrations, total soluble protein concentration and transcript abundances of BSP genes in the bark of field-grown P. x canescens harvested during two annual growth cycles. By correlation analysis and linear modelling, we assessed interactions between biological data and meteorological conditions. Day length correlated with BSP expression, and air temperature correlated strongly with total protein concentration (r = -0.92), gamma-aminobutyric acid (GABA; r = 0.76) and arginine (r = -0.70). GABA and arginine also correlated significantly with total protein concentration and transcript abundances of BSP genes. We conclude that GABA and arginine potentially contribute to adjust storage processes in the bark of poplar trees to seasonal changes in environmental conditions. PMID- 20354194 TI - Gibberellin-auxin crosstalk modulates lateral root formation. PMID- 20354195 TI - Gibberellins regulate lateral root formation in Populus through interactions with auxin and other hormones. AB - The role of gibberellins (GAs) in regulation of lateral root development is poorly understood. We show that GA-deficient (35S:PcGA2ox1) and GA-insensitive (35S:rgl1) transgenic Populus exhibited increased lateral root proliferation and elongation under in vitro and greenhouse conditions, and these effects were reversed by exogenous GA treatment. In addition, RNA interference suppression of two poplar GA 2-oxidases predominantly expressed in roots also decreased lateral root formation. GAs negatively affected lateral root formation by inhibiting lateral root primordium initiation. A whole-genome microarray analysis of root development in GA-modified transgenic plants revealed 2069 genes with significantly altered expression. The expression of 1178 genes, including genes that promote cell proliferation, growth, and cell wall loosening, corresponded to the phenotypic severity of the root traits when transgenic events with differential phenotypic expression were compared. The array data and direct hormone measurements suggested crosstalk of GA signaling with other hormone pathways, including auxin and abscisic acid. Transgenic modification of a differentially expressed gene encoding an auxin efflux carrier suggests that GA modulation of lateral root development is at least partly imparted by polar auxin transport modification. These results suggest a mechanism for GA-regulated modulation of lateral root proliferation associated with regulation of plant allometry during the stress response. PMID- 20354196 TI - F-box proteins FKF1 and LKP2 act in concert with ZEITLUPE to control Arabidopsis clock progression. AB - Regulation of protein turnover mediated by ZEITLUPE (ZTL) constitutes an important mechanism of the circadian clock in Arabidopsis thaliana. Here, we report that FLAVIN BINDING, KELCH REPEAT, F-BOX1 (FKF1) and LOV KELCH PROTEIN2 (LKP2) play similar roles to ZTL in the circadian clock when ZTL is absent. In contrast with subtle circadian clock defects in fkf1, the clock in ztl fkf1 has a considerably longer period than in ztl. In ztl fkf1 lkp2, several clock parameters were even more severely affected than in ztl fkf1. Although LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) expression levels are lower in ztl than in the wild type, introducing both fkf1 and lkp2 mutations into the ztl mutant dramatically diminished LHY expression without further affecting CCA1 expression. This demonstrates different contributions of ZTL, FKF1, and LKP2 in the regulation of LHY and CCA1 expression. In addition, FKF1 and LKP2 also interacted with TIMING OF CAB EXPRESSION1 (TOC1) and PSEUDO RESPONSE REGULATOR5 (PRR5), and both proteins were further stabilized in ztl fkf1 and ztl fkf1 lkp2 compared with in ztl. Our results indicate that ZTL, FKF1, and LKP2 together regulate TOC1 and PRR5 degradation and are major contributors to determining the period of circadian oscillation and enhancing robustness. PMID- 20354198 TI - SHORT HYPOCOTYL UNDER BLUE1 truncations and mutations alter its association with a signaling protein complex in Arabidopsis. AB - Higher plants monitor their ambient light signals through red/far-red absorbing phytochromes and blue/UV-A light absorbing cryptochromes. Subsequent signaling cascades alter gene expression and initiate morphogenic responses. We previously isolated SHORT HYPOCOTYL UNDER BLUE1 (SHB1), a putative transcriptional coactivator in light signaling. SHB1 is homologous to the SYG1 protein family and contains an N-terminal SPX domain and a C-terminal EXS domain. Overaccumulation of the SPX domain caused a long hypocotyl phenotype similar to that of shb1-D under red, far-red, or blue light. By contrast, overaccumulation of the C terminal EXS domain led to a short hypocotyl phenotype similar to that of shb1 under blue light. The N-terminal SPX domain was associated with a smaller protein complex than the native protein complex associated with endogenous SHB1. By contrast, the EXS domain was associated with a slightly smaller protein complex than the native protein complex, but it largely displaced endogenous SHB1 from its native protein complex. In addition, all six missense mutations that we identified from a suppressor screen were clustered within or close to the SPX domain, and these mutations impaired the assembly of the SHB1-containing protein complex. We propose that both SPX and EXS domains likely anchor SHB1 to a protein complex, and the SPX domain is critical for SHB1 signaling. PMID- 20354200 TI - Discovery proteomics: application to HIV infection. PMID- 20354199 TI - Sieve tube geometry in relation to phloem flow. AB - Sieve elements are one of the least understood cell types in plants. Translocation velocities and volume flow to supply sinks with photoassimilates greatly depend on the geometry of the microfluidic sieve tube system and especially on the anatomy of sieve plates and sieve plate pores. Several models for phloem translocation have been developed, but appropriate data on the geometry of pores, plates, sieve elements, and flow parameters are lacking. We developed a method to clear cells from cytoplasmic constituents to image cell walls by scanning electron microscopy. This method allows high-resolution measurements of sieve element and sieve plate geometries. Sieve tube-specific conductivity and its reduction by callose deposition after injury was calculated for green bean (Phaseolus vulgaris), bamboo (Phyllostachys nuda), squash (Cucurbita maxima), castor bean (Ricinus communis), and tomato (Solanum lycopersicum). Phloem sap velocity measurements by magnetic resonance imaging velocimetry indicate that higher conductivity is not accompanied by a higher velocity. Studies on the temporal development of callose show that small sieve plate pores might be occluded by callose within minutes, but plants containing sieve tubes with large pores need additional mechanisms. PMID- 20354201 TI - Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. AB - Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of thiopurine drugs. Patients that due to genetic variation lack this enzyme or have lower levels than normal, can be adversely affected if normal doses of thiopurines are prescribed. The evidence for measuring TPMT prior to starting patients on thiopurine drug therapy has been reviewed and the various approaches to establishing a service considered. Until recently clinical guidelines on the use of the TPMT varied by medical specialty. This has now changed, with clear guidance encouraging clinicians to use the TPMT test prior to starting any patient on thiopurine therapy. The TPMT test is the first pharmacogenomic test that has crossed from research to routine use. Several analytical approaches can be taken to assess TPMT status. The use of phenotyping supported with genotyping on selected samples has emerged as the analytical model that has enabled national referral services to be developed to a high level in the UK. The National Health Service now has access to cost-effective and timely TPMT assay services, with two laboratories undertaking the majority of the work at national level and with several local services developing. There appears to be adequate capacity and an appropriate internal market to ensure that TPMT assay services are commensurate with the clinical demand. PMID- 20354197 TI - Calcium signals: the lead currency of plant information processing. AB - Ca(2+) signals are core transducers and regulators in many adaptation and developmental processes of plants. Ca(2+) signals are represented by stimulus specific signatures that result from the concerted action of channels, pumps, and carriers that shape temporally and spatially defined Ca(2+) elevations. Cellular Ca(2+) signals are decoded and transmitted by a toolkit of Ca(2+) binding proteins that relay this information into downstream responses. Major transduction routes of Ca(2+) signaling involve Ca(2+)-regulated kinases mediating phosphorylation events that orchestrate downstream responses or comprise regulation of gene expression via Ca(2+)-regulated transcription factors and Ca(2+)-responsive promoter elements. Here, we review some of the remarkable progress that has been made in recent years, especially in identifying critical components functioning in Ca(2+) signal transduction, both at the single-cell and multicellular level. Despite impressive progress in our understanding of the processing of Ca(2+) signals during the past years, the elucidation of the exact mechanistic principles that underlie the specific recognition and conversion of the cellular Ca(2+) currency into defined changes in protein-protein interaction, protein phosphorylation, and gene expression and thereby establish the specificity in stimulus response coupling remain to be explored. PMID- 20354203 TI - Alterations in glycosylation as biomarkers for cancer detection. AB - Glycoconjugates constitute a major class of biomolecules which include glycoproteins, glycosphingolipids and proteoglycans. Glycans are involved in several physiological and pathological conditions, such as host-pathogen interactions, cell differentiation, migration, tumour invasion and metastisation, cell trafficking and signalling. Cancer is associated with glycosylation alterations in glycoproteins and glycolipids. This review describes various aspects of protein glycosylation with the focus on alterations associated with human cancer. The application of these glycosylation modifications as biomarkers for cancer detection in tumour tissues and serological assays is summarised. PMID- 20354202 TI - Spindle cell melanocytic lesions--part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions. AB - Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes reveal a dendritic cytomorphology and territorial isolation, lesional naevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may be either a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either because of its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion because of a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified. However, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions can reliably be resolved with this standard approach, problem areas do exist and cause no end of grief to the surgical pathologist or dermatopathologist. In this review, the authors present their algorithmic approach to spindle cell melanocytic lesions and discuss each entity in turn, in order to (1) model a systematic approach to such lesions, and (2) provide familiarity with those melanocytic lesions that either typically or occasionally display a spindled cytomorphology. PMID- 20354204 TI - Best practice in primary care pathology: review 12. AB - This twelfth best practice review examines four series of common primary care questions in laboratory medicine: (i) antiepileptic drug monitoring; (ii) infectious diarrhoea; (iii) methicillin resistant Staphylococcus aureus; and (iv) brain natriuretic peptide. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information. PMID- 20354205 TI - Age-related differences in granulomatous gastritis: a retrospective, clinicopathological analysis. AB - BACKGROUND: Granulomatous gastritis (GG) is an uncommon pathological finding that may accompany systemic disease, infections, foreign body reaction, malignancy or vasculitis, but may also be an isolated finding. Clinical and pathological features of GG have been systematically evaluated in adults but not children. OBJECTIVES: To compare clinical and pathological features of GG in adults and children, and also determine the prevalence of GG in children from a single centre. METHODS: A retrospective analysis of 23 children and 23 adults with GG was conducted. Demographic and clinical information was recorded for each patient. Gastric biopsy specimens were evaluated for the presence of gastritis, infectious organisms, and number and location of the granulomas. RESULTS: Children were a mean+/-SD age of 12.5+/-3.0 years, had a male predominance, and were most often Caucasian. Adults were a mean+/-SD age of 49.2+/-13.2 years, had a female predominance, and were most often African-American. Primary diagnoses were Crohn's disease in children, and sarcoidosis and isolated GG in adults. In both groups, granulomas were most often located in the antrum, with no difference in the number of granulomas per biopsy between children and adults. All biopsy specimens were negative for acid-fast bacilli and fungal organisms; Helicobacter pylori infection was uncommon. Overall prevalence of GG in children in this study was 1.7% for all diagnostic upper endoscopies. CONCLUSION: Differences in aetiology of GG between children and adults reflect age-specific disease states. Gender differences can be partially explained by gender differences intrinsic to the underlying aetiology. Irrespective of the underlying aetiology, the number and location of granulomas are similar in children and adults. PMID- 20354206 TI - An audit of the implementation of the international consensus group's guidelines on reporting of blood films. AB - AIMS: This study was carried out as part of the Pathology Benchmarking Review and it audits the implementation of the guidelines for the reporting of blood films published by the International Consensus Group for Haematology Review. METHODS: Each laboratory completed a questionnaire about the number of blood counts and blood films performed. Information was collected on the criteria that were used for preparing a blood film and whether they had followed the guidelines of the International Consensus Group. RESULTS: 74 National Health Service organisations (151 laboratory sites) participated in the study. 24 laboratories had implemented the guideline, 21 with local modification, and 3 without modification. The reasons that prevented the full implementation of the guideline included the inability of laboratory information systems to be modified to include the guideline rules, the laboratory not agreeing with the guideline criteria, and the staff time required to implement the guide to justify the perceived local benefits of implementation. CONCLUSION: This is the first study that has assessed the implementation of the International Consensus Guidelines at a national level. Many laboratories had experienced difficulty in implementing the consensus guideline partly due to the complexity of the guideline. As a result 21 of the 24 laboratories that had attempted to implement the guideline had made local modification to the guideline. Since it was not possible to estimate the impact that local modification of the guideline would have on the percentage of blood films it was not possible to establish a benchmark of practice following implementation of the guideline. PMID- 20354207 TI - In vitro susceptibility of Clostridium difficile to rifaximin and rifampin in 359 consecutive isolates at a university hospital in Houston, Texas. AB - AIM: This was an in vitro study to analyse the susceptibility of Clostridium difficile isolates to rifampin and rifaximin. METHODS: Stool samples from patients who had nosocomial diarrhoea and C difficile toxin B at a university hospital between August 2006 and December 2007 were cultured for C difficile. Susceptibility of C difficile isolates to rifaximin and rifampin was determined by agar dilution and E strips, respectively. C difficile isolates were analysed via PCR for genes encoding toxins A and B, for binary toxin (BT), and for partial deletions of the tcdC gene (tcdC-del). RESULTS: Rifaximin exhibited high-level activity against 359 C difficile isolates, with MIC(50) <0.01 microg/ml and MIC(90) 0.25 microg/ml; rifampin had MIC(50) <0.002 microg/ml and MIC(90) 4 microg/ml. Among isolates analysed, 55 (15%) were positive for BT and tcdC-del. 28 (8% of 359) isolates were resistant to rifampin (> or = 32 microg/ml), of which 6 (2% of 359) were resistant to rifaximin and rifampin with MIC values > or = 32 microg/ml. 2 of the 28 isolates resistant to rifampin were A(+)/B(+)/BT(+)/tcdC-del(+), 5 were A(+)/B(+)/BT(-)/tcdC-del(+), 4 were A(+)/B(+)/BT(+)/tcdC-del(-), 13 were A(+)/B(+)/BT(-)/tcdC-del(-), and 4 had no detectable toxin genes. Of the 11 isolates resistant to rifaximin alone, 1 was A(+)/B(+)/BT(-)/tcdC-del(+), 2 were A(+)/B(+)/BT(+)/tcdC-del(-), 6 were A(+)/B(+)/BT(-)/tcdC-del(-), and 2 had no detectable toxin genes. CONCLUSIONS: The study demonstrates that rifaximin has high-level activity against C difficile in vitro. Determination of resistance to rifampin by E strip did not predict rifaximin resistance. PMID- 20354208 TI - Progressive leukoencephalopathy caused by primary CNS lymphoma. AB - Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment. PMID- 20354209 TI - Sialadenoma papilliferum with potentially malignant features. AB - Sialadenoma papilliferum (SP) is a benign non-invasive lesion with slow and limited growth. This report describes an unusual SP that enlarged rapidly and presented as an extensive intraoral tumour highly suspicious for verrucous carcinoma. Radiographic resorption of the underlying bone was evident in the mandible. This type of destructive growth does not conform to any previously reported SP. Histological features were also atypical: surface verrucous hyperplasia and deeper florid cystic-duct adenoma. Overall, the SP is likely to be considered a borderline lesion with malignant potential. Four published cases of malignancy associated with SP showed completely different clinical and pathological settings, further obfuscating the concept of malignant SP. PMID- 20354210 TI - Extensive perinephric abscess complicated by herpes simplex virus 1 reactivation. AB - A 43-year-old man, admitted with a swollen right thigh, was diagnosed with a deep vein thrombosis. On day 6 he became septic. A CT scan demonstrated a right-sided hydronephrosis and a large retroperitoneal collection. Blood cultures and perinephric pus grew Escherichia coli resistant to amoxicillin only. On day 12 a vesicular rash appeared on the neck and herpes simplex virus 1 (HSV-1) grew on culture. On day 15 an upper leg collection was seen on CT scan. Thigh tissue specimens grew extended-spectrum beta-lactamase (ESBL) producing E coli and HSV-1 was also detected by polymerase chain reaction in the tissue. On day 18 the patient died. This case illustrates an unusual presentation and complication of a perinephric abscess. In critically ill patients herpes simplex reactivation and emergence of multiresistant organisms may occur resulting in treatment failure. PMID- 20354211 TI - Pulmonary thrombotic microangiopathy caused by gastric carcinoma. AB - Pulmonary tumour thrombotic microangiopathy (PTTM) is characterised by wide spread tumour emboli along with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles. PTTM is a rare but fatal complication of carcinoma, but the pathogenesis remains to be clarified. An autopsy case of PTTM caused by gastric adenocarcinoma is described, in which tumour cells in the PTTM lesion had positive immunoreactivity for platelet derived growth factor (PDGF) and PDGF receptor (PDGFR), and proliferating fibromuscular intimal cells also showed expression of PDGFR. In addition, the overexpression of PGDF was detected in the alveolar macrophages. These findings suggest that PDGF derived from alveolar macrophages and from tumour cells may act together in promoting fibrocellular intimal proliferation. To the best of the authors' knowledge, the possible involvement of activated alveolar macrophages in PTTM has not been previously reported. PMID- 20354212 TI - Allele-specific wild-type blocker quantitative PCR for highly sensitive detection of rare JAK2 p.V617F point mutation in primary myelofibrosis as an appropriate tool for the monitoring of molecular remission following therapy. AB - Screening of JAK2 V617F point mutation becomes more and more important in monitoring of JAK2 positive MPN following stem cell transplantation. In an attempt to achieve the required high sensitivity (1:10(5)), specifity and robustness we created an approach applicable on bone marrow biopsies where we adapted the principle of wild-type blocker PCR with allele-specific Q-PCR. The significance of the assay was demonstrated on a retrospective series of sequential bone marrow biopsies as diagnosis of molecular relapse now preceded the diagnosis of clinical relapse by far. This method offers the urgently needed tool for a systematic molecular analysis of sequential biopsies in the course of stem cell transplantation to develop guidelines for the management of these patients. PMID- 20354214 TI - Epidemiological data of common soft tissue sarcomas as seen in our practice. PMID- 20354215 TI - Patients with anaphylaxis in accident and emergency are not referred to specialised allergy services. PMID- 20354216 TI - Case report: osteoclast-like giant cell tumour of the pancreas without epithelial differentiation. PMID- 20354220 TI - Discontinuation of antihyperglycemic therapy and clinical outcomes after acute myocardial infarction in older patients with diabetes. AB - BACKGROUND: Patients with diabetes are frequently admitted for acute myocardial infarction (AMI) on antihyperglycemic agents but may be discharged without glucose-lowering therapy. We examined the frequency of this practice and evaluated the associated outcomes of readmission and mortality. METHODS AND RESULTS: We conducted a retrospective study of 24 953 Medicare beneficiaries with diabetes discharged after hospitalization for AMI. We examined the frequency of discontinuation of antihyperglycemic agents on discharge among those patients admitted on a diabetic regimen. The independent association between discharge on versus off antihyperglycemic therapy and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year for AMI, heart failure, and all causes. There were 8751 patients admitted on at least 1 antihyperglycemic agent who met our inclusion/exclusion criteria. Of these, 7581 (86.6%) were discharged on antihyperglycemic therapy and 1170 (13.4%) were discharged off antihyperglycemic therapy. After multivariable analysis, as compared with those whose diabetes therapy was continued at discharge, patients who were not prescribed a glucose-lowering agent had higher 1-year mortality rate (hazard ratio, 1.29; 95% confidence interval, 1.15 to 1.45). Readmission rates did not differ significantly between the 2 groups (hazard ratio, 0.95; 95% confidence interval, 0.87 to 1.03). CONCLUSIONS: In older patients with diabetes after AMI, discontinuation of antihyperglycemic therapy is common and associated with higher mortality rates. The reasons behind this practice as well as the specific effects of hyperglycemia after AMI merit further study. PMID- 20354221 TI - Adverse events after stopping clopidogrel in post-acute coronary syndrome patients: Insights from a large integrated healthcare delivery system. AB - BACKGROUND: A prior study from the Veterans Health Administration found a clustering of cardiovascular events after clopidogrel cessation. We sought to confirm and expand these findings. METHODS AND RESULTS: This was a retrospective cohort study of 2017 patients with acute coronary syndrome discharged on clopidogrel from an integrated health care delivery system. Rates of all-cause mortality or acute myocardial infarction (MI) within 1 year after stopping clopidogrel were assessed among patients who did not have an event before stopping clopidogrel. Death/MI occurred in 4.3% (n=71) of patients. The rates of death/MI were 3.07, 1.62, 0.70, and 0.95 per 10 000 patient-days for the time intervals of 0 to 90, 91 to 180, 181 to 270, and 271 to 360 days after stopping clopidogrel. In multivariable analysis, the 0- to 90-day interval after stopping clopidogrel was associated with higher risk of death/MI (incidence rate ratio, 2.74; 95% confidence interval, 1.69 to 4.44) compared with 91- to 360-day interval. There was a similar trend of increased events after stopping clopidogrel for various subgroups (women versus men, medical therapy versus percutaneous coronary intervention, stent type, and > or =6 months or <6 months of clopidogrel treatment). Among patients taking clopidogrel but stopping ACE inhibitor medications, the event rates were similar in the 0- to 90-day versus the 91- to 360-day interval (2.67 versus 2.91 per 10 000 patient-days; P=0.91). CONCLUSIONS: We observed a clustering of adverse events in the 0 to 90 days after stopping clopidogrel. This clustering of events was not present among patients stopping ACE inhibitors. These findings are consistent with a possible rebound platelet hyper-reactivity after stopping clopidogrel and additional platelet studies are needed to confirm this effect. PMID- 20354223 TI - GPCR dimers fall apart. AB - G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), transduce various sensory and nonsensory signals. It is now widely accepted that these receptors associate with each other as homomeric or heteromeric dimers or as higher-order oligomers. This realization raises a number of questions regarding the quaternary structure of GPCRs and the function of GPCR oligomers: How does ligand binding in one protomer affect an associated protomer? What is the functional unit that activates downstream signaling molecules? What parts of the receptor form the interfaces between protomers? Where along the pathway from synthesis to degradation do oligomers form? Do they ever dissociate? Until recently, this last question has attracted little attention, and GPCR dimers and oligomers have generally been considered to be stable structures. However, biophysical studies have now begun to address this question, and the answer that is emerging will require a reassessment of the stable dimer model. PMID- 20354224 TI - Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. AB - Reactive oxygen species (ROS) are involved in many physiological and pathophysiological cellular processes. We used lymphocytes, which are exposed to highly oxidizing environments during inflammation, to study the influence of ROS on cellular function. Calcium ion (Ca(2+)) influx through Ca(2+) release activated Ca(2+) (CRAC) channels composed of proteins of the ORAI family is essential for the activation, proliferation, and differentiation of T lymphocytes, but whether and how ROS affect ORAI channel function have been unclear. Here, we combined Ca(2+) imaging, patch-clamp recordings, and measurements of cell proliferation and cytokine secretion to determine the effects of hydrogen peroxide (H(2)O(2)) on ORAI channel activity and human T helper lymphocyte (T(H) cell) function. ORAI1, but not ORAI3, channels were inhibited by oxidation by H(2)O(2). The differential redox sensitivity of ORAI1 and ORAI3 channels depended mainly on an extracellularly located reactive cysteine, which is absent in ORAI3. T(H) cells became progressively less redox sensitive after differentiation into effector cells, a shift that would allow them to proliferate, differentiate, and secrete cytokines in oxidizing environments. The decreased redox sensitivity of effector T(H) cells correlated with increased expression of Orai3 and increased abundance of several cytosolic antioxidants. Knockdown of ORAI3 with small-interfering RNA rendered effector T(H) cells more redox-sensitive. The differential expression of Orai isoforms between naive and effector T(H) cells may tune cellular responses under oxidative stress. PMID- 20354225 TI - New roles for the LKB1-NUAK pathway in controlling myosin phosphatase complexes and cell adhesion. AB - The AMPK-related kinases NUAK1 and NUAK2 are activated by the tumor suppressor LKB1. We found that NUAK1 interacts with several myosin phosphatases, including the myosin phosphatase targeting-1 (MYPT1)-protein phosphatase-1beta (PP1beta) complex, through conserved Gly-Ile-Leu-Lys motifs that are direct binding sites for PP1beta. Phosphorylation of Ser(445), Ser(472), and Ser(910) of MYPT1 by NUAK1 promoted the interaction of MYPT1 with 14-3-3 adaptor proteins, thereby suppressing phosphatase activity. Cell detachment induced phosphorylation of endogenous MYPT1 by NUAK1, resulting in 14-3-3 binding to MYPT1 and enhanced phosphorylation of myosin light chain-2. Inhibition of the LKB1-NUAK1 pathway impaired cell detachment. Our data indicate that NUAK1 controls cell adhesion and functions as a regulator of myosin phosphatase complexes. Thus, LKB1 can influence the phosphorylation of targets not only through the AMPK family of kinases but also by controlling phosphatase complexes. PMID- 20354226 TI - The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. AB - Tumor necrosis factor (TNF) is a pleiotropic molecule with a crucial role in cellular stress and inflammation during infection, tissue damage, and cancer. TNF signaling can lead to three distinct outcomes, each of which is initiated by different signaling complexes: the gene induction or survival mode, the apoptosis mode, and the necrosis mode. The kinases receptor-interacting protein 1 (RIP1) and RIP3 are key signaling molecules in necrosis and are regulated by caspases and ubiquitination. Moreover, TNF stimulation induces the formation of a necrosome in which RIP3 is activated and interacts with enzymes that control glycolytic flux and glutaminolysis. The necrosome induces mitochondrial complex I mediated production of reactive oxygen species (ROS) and cytotoxicity, which suggest a functional link between increased bioenergetics and necrosis. In addition, other effector mechanisms also contribute to TNF-induced necrosis, such as recruitment of NADPH (the reduced form of nicotinamide adenine dinucleotide phosphate) oxidases and subsequent ROS production at the membrane-associated TNF receptor complex I; calcium mobilization; activation of phospholipase A(2), lipoxygenases, and acid sphingomyelinases; and lysosomal destabilization. However, the link between RIP1 and RIP3 and these subcellular events remains to be established. The regulation of RIP1 and RIP3 and their downstream signaling cascades opens new therapeutic avenues for treatment of pathologies associated with cell loss, such as ischemia-reperfusion damage and neurodegeneration, and ways to stimulate alternative immunogenic cell death pathways in cancer. PMID- 20354227 TI - Lehmann family of ROC curves. AB - Receiver operating characteristic (ROC) curves evaluate the discriminatory power of a continuous marker to predict a binary outcome. The most popular parametric model for an ROC curve is the binormal model, which assumes that the marker, after a monotone transformation, is normally distributed conditional on the outcome. Here, the authors present an alternative to the binormal model based on the Lehmann family, also known as the proportional hazards specification. The resulting ROC curve and its functionals (such as the area under the curve and the sensitivity at a given level of specificity) have simple analytic forms. Closed form expressions for the functional estimates and their corresponding asymptotic variances are derived. This family accommodates the comparison of multiple markers, covariate adjustments, and clustered data through a regression formulation. Evaluation of the underlying assumptions, model fitting, and model selection can be performed using any off-the-shelf proportional hazards statistical software package. PMID- 20354228 TI - Treatment evolution and new standards of care: implications for cost effectiveness analysis. AB - BACKGROUND: Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes. OBJECTIVE: To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time. DESIGN: . Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment. RESULTS: The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery. CONCLUSIONS: For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered. PMID- 20354230 TI - Altered fibroblast proliferation and apoptosis in diabetic gingival wounds. AB - Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with factors that decrease fibroblast numbers. Full-thickness wounds were created in the palatal gingiva of type 1 and type 2 diabetic and normoglycemic mice. Five days after wounding, diabetic mice had less epithelial wound coverage, less new connective tissue formation, and reduced fibroblast density (p < 0.05). This occurred with increased numbers of caspase-3- and TUNEL-positive fibroblasts, decreased fibroblast proliferation, increased nuclear translocation of the pro apoptotic transcription factor FOXO1, and increased numbers of polymorphonuclear leukocytes, all of which were significant (p < 0.05). The results suggest that diabetes may decrease fibroblast numbers through increased apoptosis and reduced proliferation, both of which may be mediated through increased activation of FOXO1. PMID- 20354229 TI - Development of inpatient risk stratification models of acute kidney injury for use in electronic health records. AB - OBJECTIVE: Patients with hospital-acquired acute kidney injury (AKI) are at risk for increased mortality and further medical complications. Evaluating these patients with a prediction tool easily implemented within an electronic health record (EHR) would identify high-risk patients prior to the development of AKI and could prevent iatrogenically induced episodes of AKI and improve clinical management. METHODS: The authors used structured clinical data acquired from an EHR to identify patients with normal kidney function for admissions from 1 August 1999 to 31 July 2003. Using administrative, computerized provider order entry and laboratory test data, they developed a 3-level risk stratification model to predict each of 2 severity levels of in-hospital AKI as defined by RIFLE criteria. The severity levels were defined as 150% or 200% of baseline serum creatinine. Model discrimination and calibration were evaluated using 10-fold cross-validation. RESULTS: Cross-validation of the models resulted in area under the receiver operating characteristic (AUC) curves of 0.75 (150% elevation) and 0.78 (200% elevation). Both models were adequately calibrated as measured by the Hosmer-Lemeshow goodness-of-fit test chi-squared values of 9.7 (P = 0.29) and 12.7 (P = 0.12), respectively. CONCLUSIONS: The authors generated risk prediction models for hospital-acquired AKI using only commonly available electronic data. The models identify patients at high risk for AKI who might benefit from early intervention or increased monitoring. PMID- 20354231 TI - Damage and reliability of Y-TZP after cementation surface treatment. AB - Zirconia-based restorations are widely used in prosthetic dentistry, but their susceptibility to post-sintering cementation surface treatments remains controversial. We hypothesized that grinding (600-grit) and alumina abrasion (50 microm, 5 sec, 0.5 MPa) affect the damage modes and reliability of zirconia core material. Monolithic CAD/CAM-machined and sintered Y-TZP plates (0.5 mm thickness) were adhesively cemented to dentin-like composite substrates. Uni axial mouth-motion cyclic contact was applied through a tungsten carbide spherical indenter (r = 3.18 mm). Results showed that zirconia core ceramic is vulnerable to lower surface radial fracture after grinding or alumina abrasion, while the as-received control chiefly fractured from load-application surface cone fracture. Significantly lower reliability of ground and alumina-abraded compared with the as-received zirconia core ceramic can be attributed to damage induced on the cementation surface. Clinical relevance concerning surface treatment protocols for zirconia framework materials prior to cementation is addressed. PMID- 20354232 TI - HRET patient safety leadership fellowship: the role of "community" in patient safety. AB - Community engagement is widely endorsed but poorly defined as a strategy to improve patient safety. With strong evidence that engaging patients can positively influence health outcomes, it is presumed that community engagement could improve patient safety. Leaning on the models from other disciplines such as public health, the adequate knowledge and application of the principles of community engagement are critical for this approach to be effective. This article provides a description of the theories supporting patient partnership and community engagement, reviews critical elements of successful community-based programs, and identifies the potential for empowering communities to improve patient safety. PMID- 20354233 TI - Behaviors that discriminate ADHD in children and adolescents: primary symptoms, symptoms of comorbid conditions, or indicators of functional impairment? AB - OBJECTIVE: The objectives of this study were to evaluate whether behaviors that differentiate children and adolescents with ADHD from those without are related to the primary diagnostic criteria (i.e., inattention and impulsivity hyperactivity), symptoms of comorbid conditions, functional impairment, or a combination, and to determine whether behaviors that discriminate are consistent between the key developmental stages of childhood and adolescence. METHOD: Parents and teachers rated children and adolescents with a formal diagnosis of ADHD and those without any mental, physical, or emotional disorders on the multidimensional Behavior Assessment System for Children (2nd ed., BASC-2). RESULTS: Results indicated that behaviors that discriminate children and adolescents with ADHD from those without were associated with primary symptoms, symptoms of comorbid conditions, and indicators of functional impairment. Teachers rated atypicality as the strongest discriminator of children with ADHD from those without and learning problems as the strongest discriminator of adolescents. Parents rated hyperactivity as the strongest discriminator for children and attention problems for adolescents. Activities of daily living was the third strongest discriminator of adolescents as rated by parents. CONCLUSIONS: Findings supported the need for a multidimensional view of ADHD that adds emphasis to issues of functional impairment in routine, daily activities important to success in school and interpersonally. Findings showed that conceptualizing and assessing behaviors demonstrated by children and adolescents with ADHD as a whole instead of only equating a diagnosis of ADHD to hyperactivity, inattention, and impulsivity will establish a foundation for understanding, interpreting, and addressing students' academic and behavioral needs across the home and school. PMID- 20354234 TI - Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects. AB - Absorption, metabolism, and excretion of one 80 mg oral dose of [(14)C] febuxostat ([thiazole-4-(14)C] 2-[3-cyano-4-isobutoxyphenyl]-4-methyl-5 thiazolecarboxylic acid) were studied in 6 healthy subjects. Mean cumulative recovery in excreta was 94% (49% urine and 45% feces) of the dose over 9 days; 87% of the dose was profiled. Seventeen radioactive peaks were observed in urine and fecal chromatograms. Unchanged febuxostat contributed to a combined total in excreta of 10% to 18% of the dose, indicating that it was extensively metabolized and well absorbed. Metabolites were 67M-1 (10%) and 67M-2 (11%) hydroxylated febuxostat, febuxostat acyl-glucuronide (30%), 67M-4 di-carboxylic acid (14%), 67M-1 sulfate conjugate (3%), and dehydrated 67M-1/67M-2 acyl-glucuronide (0.5%). Febuxostat and these metabolites accounted for 82% of profiled dose; unidentified peaks individually contributed <1.3% of the dose. Febuxostat and total radioactivity plasma C(max) values were observed at 0.5 hour postdose, suggesting that febuxostat was quickly absorbed. At 4 hours postdose, plasma chromatographic profiles contained 6 peaks: febuxostat (85%), 67M-1 (4%), 67M-2 (5%), febuxostat acyl-glucuronide (4%), 67M-4 (1%), and 67M-1 sulfate (0.5%). Compared to total radioactivity, febuxostat accounted for 94% at C(max) and 83% of the area under the concentration-time curve (AUC) values. Based on the whole blood to plasma total radioactivity, little radioactivity was associated with red blood cells. PMID- 20354235 TI - Serum transaminase levels should be measured immediately prior to dosing in early phase I clinical trials. AB - Observations of predose spikes in transaminases from a phase I study prompted our review of other clinical trials, including 250 healthy participants from 4 studies at 3 sites. Six of these participants (2.4%) displayed elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels immediately predose despite normal values <48 hours previously, including one with ALT/AST = 237/175 IU/L (previously 41/29 IU/L). Testing immediately prior to dosing can exonerate a study drug and avoid unnecessary, expensive delays in early clinical trials. PMID- 20354236 TI - Differences in perceptions of the diagnosis and treatment of obstructive sleep apnea and continuous positive airway pressure therapy among adherers and nonadherers. AB - Obstructive sleep apnea (OSA) patients' consistent use of continuous positive airway pressure (CPAP) therapy is critical to realizing improved functional outcomes and reducing untoward health risks associated with OSA. We conducted a mixed methods, concurrent, nested study to explore OSA patients' beliefs and perceptions of the diagnosis and CPAP treatment that differentiate adherent from nonadherent patients prior to and after the first week of treatment, when the pattern of CPAP use is established. Guided by social cognitive theory, themes were derived from 30 interviews conducted postdiagnosis and after 1 week of CPAP use. Directed content analysis, followed by categorization of participants as adherent/nonadherent from objectively measured CPAP use, preceded across-case analysis among 15 participants with severe OSA. Beliefs and perceptions that differed between adherers and nonadherers included OSA risk perception, symptom recognition, self-efficacy, outcome expectations, treatment goals, and treatment facilitators/ barriers. Our findings suggest opportunities for developing and testing tailored interventions to promote CPAP use. PMID- 20354237 TI - Breast cancer messaging for younger women: gender, femininity, and risk. AB - Evidence linking both active smoking and secondhand smoke exposure to premenopausal breast cancer makes the development of health messages specific to younger women a pressing priority. To determine how to communicate information about this modifiable breast cancer risk to young women, we analyzed a selection of 32 recent English-language breast cancer messages and campaigns that targeted young women. In addition, we obtained young women's responses to three breast cancer campaign images during focus group discussions. A visual analysis of messages points to an explicitly gendered discourse within contemporary campaigns, one that entails conflicting messages regarding breast cancer, health, feminine beauty, and risk. Although the intent might be to educate and empower young women to "fight" against breast cancer, paradoxically, the messages employ imagery that sexually objectifies young women's breasts and bodies. Recommendations are made for messaging about tobacco and breast cancer risk to avoid reproducing one-dimensional or stereotypical presentations of gender and femininity. PMID- 20354238 TI - Sterilization decision making among medically at-risk obese pregnant women. AB - In this article, we describe a study using a qualitative, naturalistic grounded theory design to explore sterilization decision making by pregnant obese women. Semistructured interviews of women who intended to undergo sterilization at the time of delivery were conducted in the third trimester of pregnancy (n = 15) and again postpartum (n = 11). The decision for sterilization was based on personal criteria for family composition and the nature of each woman's relationship with her partner. The process of decision making began with developing a personal comfort with cessation of childbearing, followed by social confirmation, informing the provider, and then awaiting the procedure. Sterilization was seen as reversible, despite a desire for "something permanent." Obesity was rarely viewed as related to any part of the decision for or against sterilization, and was rarely discussed by providers. Participants made sterilization decisions in their personal and social contexts, and then shared the decision with their providers, whom they often perceived as challenging that decision. PMID- 20354239 TI - Sleep well, think well: sleep-wake disturbance in mild cognitive impairment. AB - While literature suggests that sleep is important for cognition and mood, and that sleep disturbance is a prominent feature of neurodegenerative and neuropsychiatric disorders, these relationships have not yet been examined in older people ''at risk" of dementia. In this study, 15 older people with the nonamnestic subtype of mild cognitive impairment ([MCI] mean age = 66.7 years, SD = 8.7) underwent psychiatric and neuropsychological assessment. Participants completed sleep diaries, questionnaires, and 2 weeks of actigraphy. Key outcome data during the rest interval were time spent ''awake" or wake after sleep onset (WASO) and the number of arousals/wake bouts. Results showed that even after controlling for age, greater WASO was associated with reduced attention and executive functioning and increased arousals were related to poorer nonverbal learning and problem solving. This preliminary data suggests that sleep-wake disturbance in nonamnestic forms of MCI is related to cognitive functioning and may be indicative of shared neurobiological underpinnings. PMID- 20354240 TI - Zero tolerance to asthma death. PMID- 20354241 TI - Are Hong Kong doctors following the Global Initiative for Asthma guidelines: a questionnaire "Survey on Asthma Management"? AB - OBJECTIVE: To assess the standard of asthma management by doctors in Hong Kong. DESIGN: Cross-sectional postal questionnaire survey. SETTING: Hong Kong. PARTICIPANTS: Practising doctors registered with the Medical Council of Hong Kong were sent a questionnaire between August and December 2007. MAIN OUTCOME MEASURES: Respondents' responses to questions on demographic data, parameters routinely used to assess asthma control, the pattern of asthma medication prescribing, and seven different case scenarios assessing their ability to classify asthma control and management. RESULTS. We received 410 completed questionnaires from general practitioners (55%), internists (22%), paediatricians (11%), and other specialists (12%). The majority (82%) explained the pathology of asthma to at least some of their patients and tried to identify aggravating factors of the asthma (91%). Fewer observed the inhalation technique of their patients (68%) and prescribed a written asthma management plan (33%). The main medications prescribed to adults and children with asthma were inhaled corticosteroids, inhaled short-acting beta-2 agonists, and combinations of an inhaled corticosteroid and a long-acting beta-2 agonist. In adults and children, long-acting beta-2 agonist alone (without inhaled corticosteroid) was being used to treat asthma by 45% and 36% of the doctors, respectively. Also, 94% of the respondents correctly classified the control status in four out of the seven case scenarios and 31% chose the correct medications when responding to seven of the 14 questions asked. CONCLUSIONS: Asthma management practice of Hong Kong doctors falls short of the standards recommended by international guidelines. More effort in improving their knowledge is urgently warranted. PMID- 20354242 TI - Management of primary spontaneous pneumothorax in Chinese children. AB - OBJECTIVES: To (1) determine the demographics of Chinese children admitted with primary spontaneous pneumothorax, (2) suggest how they may be quantified radiologically, (3) compare the difference in outcomes after their primary management by thoracentesis and chest tube insertion, and (4) review the local experience with surgical intervention for such children. DESIGN: Retrospective, descriptive study. SETTING: Acute tertiary public hospital, Hong Kong. PATIENTS: Consecutive patients younger than 18 years and admitted with primary spontaneous pneumothorax between 1 January 1999 and 30 September 2007. MAIN OUTCOME MEASURES: Hospital stay and risk of recurrence after thoracentesis versus chest tube insertion. RESULTS. Seventy-seven patients with 114 episodes of primary spontaneous pneumothorax were reviewed. They were significantly taller (P<0.001) and thinner (P<0.001) than the population mean percentile. Both the Light index and Collins formula were accurate in quantifying pneumothorax volume, but as the former was simpler and more user-friendly, this was more applicable in children. Thoracentesis resulted in shorter hospital stays (mean, 4.6; standard deviation, 1.9 days) than chest tube insertion (6.9; 3.0 days), but there was no significant difference in the recurrence rates within 6 months (P=1.0), 1 year (P=0.9), and 2 years (P=0.1). Insignificant pneumothorax was treated with observation alone in 16% of the patients. For patients with a clinically significant pneumothorax, thoracentesis and chest tube insertion were successful in 78% and 67%, respectively (P=0.34). The success rate of video-assisted thoracoscopic surgery was 89%, and postoperative recurrence occurred more commonly in patients without a lung bleb. CONCLUSION: Chinese children with primary spontaneous pneumothorax exhibited similar demographic characteristics to Caucasian children. Light index is simple and accurate for quantifying pneumothorax volume in children. Conservative treatment including observation, thoracentesis, and chest tube insertion should suffice for most patients with first episode of primary spontaneous pneumothorax. Early surgery is warranted for any patient who fails conservative treatment, for which video-assisted thoracoscopic surgery is safe and effective. PMID- 20354243 TI - Patient safety in the undergraduate curriculum: medical students' perception. AB - OBJECTIVE: Patient safety has emerged as a distinct health care discipline and an undergraduate programme on patient safety is being introduced at the authors' institution. The present study aimed to assess medical students' perceptions and knowledge on patient safety issues. DESIGN: A self-administered voluntary questionnaire survey. SETTING: Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. PARTICIPANTS: A total of 130 fourth-year medical students. MAIN OUTCOME MEASURES: Students' baseline perceptions and knowledge on patient safety issues. RESULTS: The majority of students agreed that medical errors were inevitable but over 25% opined that "competent physicians do not make errors". The majority disapproved the practice of non-disclosure of error; whilst 6% would not address 'near-miss' events, and almost 10% did not support an active reporting system. Nearly half of the students were neutral on the notion that uncertainty should not be tolerated in patient care, and over 80% agreed that the most effective strategy to prevent error was "to work harder and be more careful". A knowledge gap in patient safety issues existed. Over 80% of students supported the introduction of our new undergraduate programme. CONCLUSION: Medical students were aware of medical errors being an inevitable barrier between intended 'best care' and what was actually provided to patients. Students appeared to lack the appreciation of non-physician-based causes of errors, and the importance of a multidisciplinary approach to the management of incidents. A formal curriculum on patient safety is urgently needed in this locality, and such an initiative was supported by the medical students who were surveyed. PMID- 20354244 TI - The concepts of family doctor and factors affecting choice of family doctors among Hong Kong people. AB - OBJECTIVES: To identify concepts including misconceptions among the community members regarding family doctors, and determine factors affecting decisions on which doctor to consult in different clinical scenarios. DESIGN: Household telephone survey conducted between 4 and 13 September 2006. SETTING: Hong Kong community. PARTICIPANTS: Cantonese-speaking Hong Kong residents aged 18 years or more were targeted. Randomly selected participants were asked to complete a questionnaire, which was designed based on a literature search and subsequent focus group discussions. RESULTS: Among the 1811 households with eligible subjects to survey, 1204 completed the questionnaire (response rate, 67%). More than 85% considered a family doctor to be the first doctor they wanted to see even if it was inconvenient. "Clearly knowing my physical conditions", "fast acting and effective treatment", and "doctor with friendly and sincere attitude" were the three most important factors influencing the choice of a family doctor. When affected by flu-like symptoms, 65% would go to a private clinic, 20% to a general out-patient clinic, 6% to a designated clinic with staff approved by their respective medical insurance/medical benefit scheme, and 5% to a private hospital outpatient clinic. Among the latter two groups, 65% consulted the same doctor every time when they felt sick. More than 50% of those willing to have regular follow-up by a family doctor for hypertension and diabetes paid more than HK$300 per month. Approximately 64% might consider having regular follow-up at a general out-patient clinic by a nurse specialist. CONCLUSION: Hong Kong inhabitants already have their own ideas regarding how to care for their own health, and what kind of family doctors they prefer. This survey should help both doctors and health care policy makers to realign their current thinking, and thus provide a platform for the development of a primary care model unique to Hong Kong. PMID- 20354245 TI - Peri-operative blood transfusion increases length of hospital stay and number of postoperative complications in non-cardiac surgical patients. AB - OBJECTIVES: To test the hypothesis that blood transfusion alone was a significant risk factor for in-hospital morbidity in non-cardiac patients. DESIGN: Propensity analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive non-cardiac patients seen in our department from 2006 to early 2009 who underwent a major procedure under general or spinal anaesthesia were included. Propensity analysis was performed to neutralise the confounding effects of preoperative variables and identify the true effects of transfusions on surgical outcomes. MAIN OUTCOME MEASURES: Receipt of intra-operative and postoperative blood transfusion was established and the difference in proportions between patients who did and did not receive donor blood tested for mortality, overall morbidity, individual complications, and number of adverse events. RESULTS: Transfused patients were significantly older and sicker, more likely to be male, to have lower haemoglobin values and undergo longer and more emergency surgical procedures than those not receiving a transfusion. Blood transfusion was predictive of length of postoperative hospital stay and number of complications before discharge. The amount of transfused blood was predictive of in-hospital mortality, with an odds ratio of 1.4 for each unit of blood received. The risk of a surgical wound infection was almost doubled when the patient had received a blood transfusion. CONCLUSION: After controlling for the factors associated with an increased likelihood for receiving a blood transfusion, the actual transfusion was predictive of a slower and more eventful postoperative recovery with associated costs to both the patient and health services. PMID- 20354246 TI - Endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases: local experience of a novel investigation. AB - OBJECTIVE: To study the efficacy and safety of endoscopic ultrasonography-guided fine-needle aspiration in the management of mediastinal diseases in Hong Kong. DESIGN: Retrospective review of prospectively collected data. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 125 consecutive patients with various mediastinal and pulmonary lesions that underwent trans-oesophageal endoscopic ultrasonography-guided fine-needle aspiration from July 1998 to June 2007. MAIN OUTCOME MEASURES: The diagnostic accuracy and safety of the procedure and its influence in patient management. RESULTS: Malignancy was confirmed in 62 (50%) of the patients and excluded in 42 (34%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of endoscopic ultrasonography-guided fine-needle aspiration in diagnosing mediastinal malignancies were 75% (95% confidence interval, 64-83%), 100% (90-100%), 100% (93 100%), 67% (54-78%), and 83%, respectively. Eighty-six (69%) of the patients had their initial plan of invasive investigations changed. Only one (0.8%) patient developed a septic complication in a mediastinal cyst after puncturing, and was treated surgically. CONCLUSIONS: Trans-oesophageal endoscopic ultrasonography guided fine-needle aspiration is a minimally invasive, effective, and safe method of diagnosing malignant mediastinal disease. It may reduce the need for other invasive investigations. PMID- 20354247 TI - Endoscopic carpal tunnel release: experience of surgical outcome in a Chinese population. AB - OBJECTIVE: To review the outcomes of endoscopic carpal tunnel release in a Hong Kong public hospital and identify any predictive factors. DESIGN: Retrospective study. SETTING: Regional hospital with a hand surgery service, Hong Kong. PATIENTS: Between January 2001 and December 2007, records of 145 patients (160 carpal tunnel syndromes) having endoscopic release were reviewed. Five major symptom domains (pain, numbness, nocturnal awakening, weakness, and clumsiness) before and after the operation were scrutinised. Functional status was assessed by grading key pinch and hand grip, as well as complications. INTERVENTION: Endoscopic carpal tunnel release using the modified Chow's extrabursal technique under intravenous anaesthesia. RESULTS: After the 160 procedures performed, 124 (78%) and 132 (83%) of them revealed improvement in terms of numbness and nocturnal awakening, respectively. Also, there were significant improvements in terms of average functional grading of pinch power and grip power. No serious complications due to the surgery were encountered. CONCLUSIONS: Experience using the Chow's two-portal endoscopic technique for the treatment of carpal tunnel syndrome in the Chinese population was encouraging. It was a safe and effective method for treating carpal tunnel syndrome. We advocate endoscopic surgical intervention for patients with refractory relief of symptoms following conservative management. PMID- 20354248 TI - Laparoscopic management of three rare types of ectopic pregnancy. AB - The laparoscopic management of three rare types of ectopic pregnancy, including rudimentary horn pregnancy, caesarean scar pregnancy, and interstitial pregnancy is described. All were managed with little morbidity. When the appropriate facilities and skills are available, laparoscopic surgery is the surgical treatment of choice for the various types of ectopic pregnancy. PMID- 20354250 TI - Mammary angiosarcoma in two patients at either end of the age spectrum. AB - Angiosarcoma of the breast is rare and has a poor prognosis due to its aggressive nature. This is a report of two patients with mammary angiosarcomas, each with different clinical presentations, and at either end of the age spectrum. One is an 18-year-old woman who presented with a rapidly enlarging breast mass, and the other a 72-year-old woman whose breast mass was found during screening mammography. The radiological features of mammary angiosarcoma are summarised in this report. PMID- 20354249 TI - Intraventricular amphotericin for absidiomycosis in an immunocompetent child. AB - Brain abscesses are uncommon in children. We report a 3-year-old, previously healthy and immunocompetent boy, with an Absidia brain abscess. He presented with decreased sensorium and status epilepticus. The brain abscess was detected using cranial computed tomography and magnetic resonance imaging, and the diagnosis was confirmed with pus and brain tissue cultures. The patient responded to surgical drainage with concomitant intravenous and intraventricular amphotericin B. PMID- 20354251 TI - Osteonecrosis of the jaw after oral bisphosphonate for osteoporosis. AB - Bisphosphonates are a common treatment for osteoporosis. Osteonecrosis of the jaw has been associated with the use of bisphosphonates, usually when they have been used parenterally to treat malignancies. Cases associated with oral bisphosphonate as a treatment for osteoporosis are less frequent. We describe two patients exhibiting the clinical manifestations of bisphosphonate-associated osteonecrosis of the jaw. A brief review of the literature on the incidence, possible risk factors, and practice guidelines is also presented. PMID- 20354252 TI - Immunoglobulin G4-associated sclerosing cholangitis mimicking cholangiocarcinoma. AB - Immunoglobulin G4-related lymphoplasmacytic sclerosing disease is an emerging disease. Recently, it has been shown to be responsible for autoimmune pancreatitis-induced strictures of the bile duct mimicking cholangiocarcinoma. Making a diagnosis of immunoglobulin G4-associated sclerosing cholangitis requires a high index of suspicion. The differential diagnoses include primary sclerosing cholangitis, cholangiocarcinoma, and pancreatic cancer. The preoperative diagnosis is likely to be missed due to the lack of specific symptoms; a clinical presentation that may mimic other disorders, especially malignant biliary strictures; and the lack of specific imaging features. This article reports on a 51-year-old man with immunoglobulin G4-associated sclerosing cholangitis without autoimmune pancreatitis. He underwent resection of his extrahepatic bile duct with a hepaticojejunostomy. The diagnosis was confirmed after a histopathological examination. This case highlights the obstacles to making a preoperative diagnosis of immunoglobulin G4-associated sclerosing cholangitis. PMID- 20354253 TI - The first report of a single-port laparoscopic nephrectomy in a child. AB - There has been an exponential rise in the use of minimally invasive procedures in surgery, with obvious benefits to patients. Recently, transumbilical single-port laparoscopic surgery has been championed as the next major technical advance. In this article, we report the first case where single-port laparoscopic surgery has been used to manage a paediatric problem in the region. PMID- 20354254 TI - Sudden loss of vision. PMID- 20354255 TI - Mycotic cystic artery pseudoaneurysm successfully treated with transcatheter arterial embolisation. PMID- 20354256 TI - Pre-clinical year medical students: at-risk of contracting swine flu. PMID- 20354257 TI - Re: If not appendicitis, then what else can it be? A retrospective review of 1492 appendectomies. PMID- 20354258 TI - Adverse events after flu vaccination in patients with immune disorders. PMID- 20354259 TI - [Molecular mechanisms of parthenolide's action: Old drug with a new face]. AB - Parthenolide, a sesquiterpene lactone derived from the leaves of feverfew (Tanacetum parthenium), is considered a main bioactive component of this herb. Feverfew has been used orally or as an infusion for the treatment of migraine, arthritis, fever, and stomachache. Besides its anti-inflammatory and anti migraine properties, parthenolide also shows anticancer activities in a variety of cell lines. It contains an alpha-methylene-gamma-lactone ring and an epoxide moiety which are able to interact with nucleophilic sites of biologically important molecules. Parthenolide modulates multiple targets, thereby contributing to its various in vitro and in vivo effects. Inhibition of NF-kappaB activity, constitutive in many types of cancers, via either interaction with IKK or more directly with the p65 subunit of NF-kappaB, is considered one of the main mechanisms of its action. In addition, inhibition of STAT and MAP kinase activities and the induction of sustained JNK activity as well as p53 activity via influencing MDM2 and HDAC1 levels lead to an increased susceptibility of cancer cells to chemo- and radiotherapy. At the epigenetic level, parthenolide reduces HDAC1 level and, by inhibiting DNMT2 activity, induces global hypomethylation of DNA, which can restore the expressions of some suppressor genes. Moreover, this compound reduces the cellular level of GSH in cancer cells, followed by ROS accumulation and apoptosis. A unique property of parthenolide is its ability to induce cell death mainly in cancer cells, while sparing healthy ones and it also protects normal cells from UVB and oxidative stress. More remarkably, it seems to have the potential to target some cancer stem cells. Its wide array of biological activity and low toxicity make parthenolide a very promising drug with multi-pharmacological potential, largely dependent on the cellular context. PMID- 20354260 TI - [Anti-inflammatory pro-resolving derivatives of omega-3 and omega-6 polyunsaturated fatty acids]. AB - Inflammation is a physiological defense reaction of living tissues to injury or infection. An array of mediators, including those derived from omega-6 (omega6) polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) e.g. prostaglandins and leukotrienes, promote the inflammatory response. Acute inflammation has several programmed fates, including complete resolution or progression to chronic inflammation, scarring, and eventual loss of tissue function. Studies on AA-derived proinflammatory mediators led to the discovery of AA-derived anti-inflammatory and pro-resolving compounds. These include lipoxins, originating from AA, and resolvins, originating from the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as the omega-6 PUFA docosapentaenoic acid (DPA-omega6). DHA is also a substrate for other anti inflammatory mediators, i.e. neuroprotectin and maresin. Because of their role in the final phase of acute inflammation, i.e. the resolution of inflammation, the above anti-inflammatory mediators were named pro-resolving mediators. They are formed in cooperating cells present in the region of inflammation in a process called transcellular biosynthesis with the aid of specific lipoxygenases (LOX) and cyclooxygenases (COX). Pro-resolving anti-inflammatory mediators exert their biological activities in a receptor-dependent manner in the resolution phase of inflammation. Of their various biological effects, the most important include inhibition of leukocyte mobilization and traffic through endothelial or epithelial layers, suppression of proinflammatory cytokine release by different cells present in inflamed tissue, and stimulation of the phagocytic activity of monocytes/macrophages. This article surveys the current knowledge on inflammation and the role of the pro-resolving and anti-inflammatory potential of lipid derived agonistic mediators. PMID- 20354261 TI - [Physiology and molecular mechanism of glucocorticoid action]. AB - Endogenous glucocorticoids (GCs) are secreted into the systemic circulation from the adrenal cortex. This release is under the control of the circadian clock and can be enhanced at any time in response to a stressor. The levels of circulating GC are regulated systemically by the hypothalamo-pituitary-adrenal axis and locally by access to target cells and pre-receptor metabolism by 11beta hydroxysteroids dehydrogenase enzymes. GCs mediate their genomic action by binding to two different ligand-inducible transcription factors: high-affinity mineralocorticoid receptor (MR) and 10-fold lower affinity glucocorticoid receptors (GRs). Responses to GCs vary among individuals, cells, and tissues. The diversity and specificity in the steroid hormone's response in the cell is controlled at different levels, including receptor translocation, interaction with specific transcription factors and coregulators, and the regulation of receptor protein levels by microRNA. Moreover, multiple GR isoforms are generated from one single GR gene by alternative splicing and alternative translation initiation. These isoforms all have unique tissue distribution patterns and transcriptional regulatory profiles. Furthermore, each is subjected to various post-translational modifications that affect receptor function. Deciphering the molecular mechanisms of GC action is further complicated by the realization that GCs can induce rapid, non-genomic effects within the cytoplasm. A tight regulation of GC secretion and their cell-specific activity is essential for proper organism function. This is particularly seen under conditions of GC deficiency or excess, as in Addison's disease and Cushing's syndrome, respectively. PMID- 20354262 TI - [The role of interleukin 13 and interleukin 5 in asthma]. AB - Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play roles. Interleukins 5 (IL-5) and 13 (IL-13) are cytokines which play important roles in the pathophysiology of asthma. Selective accumulation and activation of eosinophils in the bronchial mucosa is considered a central event in the pathogenesis of asthma. IL-5 acts as a mediator of activation of eosinophils, influencing adhesion, membrane receptor expression, chemotaxis, and mediator synthesis. Airway eosinophilia has been related to bronchial hyperreactivity, asthma symptoms, and airway narrowing in subjects with asthma. IL-13 has a great influence on bronchial hyperreactivity, inflammation, and airway remodeling. Moreover, this cytokine drives many cellular responses relevant in asthma, including epithelial cell maturation and mucus production, synthesis of extracellular matrix proteins, and enhanced contractility of airway smooth muscle cells. In recent years, efforts have been underway to use substances acting as antagonists of these cytokines in the treatment of asthma. Many studies are being performed to assess the efficacy of anti-IL-5 and anti-IL 13 antibodies as well as substances inactivating receptors of these cytokines in asthma therapy. The results of these studies seem very interesting and induced the authors to discuss this issue. PMID- 20354263 TI - [The role of T-regulatory cells in the pathogenesis of immunological disturbances accompanying obesity and atherosclerosis]. AB - Obesity and atherosclerosis, and their consequences, including cardiovascular disease, are plagues of the 21st century. Chronic inflammation, whose mechanism is not well understood, underlies the pathophysiological bases of both processes. T lymphocytes, macrophages, and the proinflammatory cytokines produced by these cells play key roles in the immunological disturbances accompanying obesity and atherosclerosis. It was recently shown that T-regulatory cells can play a role in these processes. T-regulatory cells are a small subpopulation of T cells which are responsible for inhibition of the immune response. In this review, experiments conducted in mice and human models on the role of diminished number and/or function of T-regulatory lymphocytes in the pathogenesis of immune disturbances accompanying obesity and atherosclerosis are discussed. The results of studies using T-regulatory cells to stabilize and decrease atherosclerotic lesions in blood vessel walls are also summarized. The results of experiments performed so far are encouraging and give some hope for the future use of T regulatory cells in the therapy of obesity and atherosclerosis. PMID- 20354264 TI - [Gemini surfactants as gene carriers]. AB - Gemini surfactants are a new class of amphiphilic compounds built from two classic surfactant moieties bound together by a special spacer group. These compounds appear to be excellent for creating complexes with DNA and are effective in mediating transfection. Thanks to their construction, DNA carrier molecules built from gemini surfactants are able to deliver genes to cells of almost any DNA molecule size, unattainable when using viral gene delivery systems. Moreover, they are much safer for living organisms. PMID- 20354265 TI - [Dendritic cell-regulatory T-cell interaction]. AB - The one of the main modes of homeostasis protection is maintaining the balance between antimicrobial immunological reactions and mechanisms involved in immune response suppression. The interaction between dendritic and T cells plays a crucial role in inducing both an immune response and immunological tolerance. Dendritic cells are also able to affect the differentiation, migration, and activation of CD4+ T cells using cell-to-cell contact and/or cytokine production. The proper cytokine microenvironment can influence the induction of FoxP3 transcription factor in T cells, determining the regulatory properties of these cells. However, it is still unclear what is more substantial for Treg induction: the cytokines in the microenvironment, stimulation by a specific DC population, or the type of antigens presented by DC. Activated natural Treg as well as induced Treg cells use similar mechanisms to generate tolerance, for example by the production of such anti-inflammatory cytokines as TGF-beta or IL-10 and by direct contact with target cells. Recently, some reports have described the possibility that Treg cells lose FoxP3 expression followed by loss of suppressive function directed against proliferating T lymphocytes. PMID- 20354266 TI - The role of the nuclear pore complex in aging of post-mitotic cells. PMID- 20354267 TI - Light-at-night, cancer and aging. PMID- 20354268 TI - The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. AB - The thymus is the major site of T cell production and a key organ of the immune system. Its natural involution during the course of life has cast doubts as to its importance for the integrity of our immunity in adulthood. We provide here an overview of the recent works focusing on the immunological evaluation of subjects thymectomized during early childhood due to cardiac surgery of congenital heart defects. These studies represent new advances in our appreciation of the role of the thymus in humans and more generally in our understanding of the development of immunosenescence. PMID- 20354269 TI - Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in young but not in old rats. AB - We evaluated the effect of exposure to constant light started at the age of 1 month and at the age of 14 months on the survival, life span, tumorigenesis and age-related dynamics of antioxidant enzymes activity in various organs in comparison to the rats maintained at the standard (12:12 light/dark) light/dark regimen. We found that exposure to constant light started at the age of 1 month accelerated spontaneous tumorigenesis and shortened life span both in male and female rats as compared to the standard regimen. At the same time, the exposure to constant light started at the age of 14 months failed to influence survival of male and female rats. While delaying tumors in males, constant light accelerated tumors in females. We conclude that circadian disruption induced by light-at night started at the age of 1 month accelerates aging and promotes tumorigenesis in rats, however failed affect survival when started at the age of 14 months. PMID- 20354271 TI - Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation? AB - By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post-transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1alpha pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum-localized enzymes, and leads to impaired lipid metabolism. We will describe here the additional pathways synchronized by the clock and discussed the influence of the circadian clock-controlled feeding rhythm on them. PMID- 20354270 TI - Age-associated epigenetic modifications in human DNA increase its immunogenicity. AB - Chronic inflammation, increased reactivity to self-antigens and incidences of cancer are hallmarks of aging. However, the underlying mechanisms are not well understood. Age-associated alterations in the DNA either due to oxidative damage, defects in DNA repair or epigenetic modifications such as methylation that lead to mutations and changes in the expression of genes are thought to be partially responsible. Here we report that epigenetic modifications in aged DNA also increase its immunogenicity rendering it more reactive to innate immune system cells such as the dendritic cells. We observed increased upregulation of costimulatory molecules as well as enhanced secretion of IFN-alpha from dendritic cells in response to DNA from aged donors as compared to DNA from young donors when it was delivered intracellularly via Lipofectamine. Investigations into the mechanisms revealed that DNA from aged subjects is not degraded, neither is it more damaged compared to DNA from young subjects. However, there is significantly decreased global level of methylation suggesting that age-associated hypomethylation of the DNA may be the cause of its increased immunogenicity. Increased immunogenicity of self DNA may thus be another mechanism that may contribute to the increase in age-associated chronic inflammation, autoimmunity and cancer. PMID- 20354272 TI - The Janus face of DNA methylation in aging. AB - Aging is arguably the most familiar yet least-well understood aspect of human biology. The role of epigenetics in aging and age-related diseases has gained interest given recent advances in the understanding of how epigenetic mechanisms mediate the interactions between the environment and the genetic blueprint. While current concepts generally view global deteriorations of epigenetic marks to insidiously impair cellular and molecular functions, an active role for epigenetic changes in aging has so far received little attention. In this regard, we have recently shown that early-life adversity induced specific changes in DNA methylation that were protected from an age-associated erasure and correlated with a phenotype well-known to increase the risk for age-related mental disorders. This finding strengthens the idea that DNA (de-)methylation is controlled by multiple mechanisms that might fulfill different, and partly contrasting, roles in the aging process. PMID- 20354273 TI - PVP versus HoLEP current outcomes and future strategies. AB - Photoselective vaporization of the prostate (PVP) with a potassium titanyl phosphate (KTP) laser and Holmium laser enucleation of the prostate (HoLEP) currently represent the most promising new technologies applied to the treatment of benign prostatic hyperplasia (BPH) associated with benign prostatic obstruction (BPO). The specific laser-light characteristics and the optimal interactions between lasers and prostatic tissue result in an even and efficient ablation of the prostate resulting in the formation of a clearly de-obstructed prostate cavity. PVP and HoLEP can be considered day-case procedures, as they require only a few hours of catheterization and are associated with minimal postoperative discomfort, while at the same time they offer results at least equivalent to the reference standards transurethral resection of the prostate and open prostatectomy. There is no doubt that larger studies with longer follow up are necessary to further define the durability of results of PVP and HoLEP in the management of BPH, this review will address current issues regarding how both techniques are performed, their results and limitations as well as their role in the future management of BPH. PMID- 20354274 TI - Anecdotes and "serendipities" in American urology: Hugh Hampton Young. AB - Short review of the life and achievements of Hugh Hampton Young, inventor, supporter of the arts, great surgeon and teacher and innovator. A urologist by accident, he became the father of American Urology and influenced the growth of his chosen profession across the globe. PMID- 20354275 TI - Effectiveness of two ultrasound-guided transrectal biopsy schemes in the diagnosis of prostate cancer. A randomized study. AB - OBJECTIVE: To determine whether a 10-core prostate biopsy scheme is superior to the sextant scheme in diagnosing prostate cancer in patients programmed for a first biopsy, with negative rectal digital examination and PSA between 3.5-20 ng/ml. METHODS: A randomized prospective study was performed comparing two prostate biopsy schemes, with randomization stratification according to prostate volume (< or = 50 ml and > 50 ml). Sample size predetermination yielded a minimum of 304 patients in order to achieve the primary objective. Statistical analysis was carried out on an intent-to-treat basis, using the chi-squared test and uni- and multivariate analysis via logistic regression. RESULTS: Cancer was detected in 27.3% of the cases. A significant association was observed between cancer diagnosis and age (p=0.03), prostate volume (p=0.0001) and ultrasound nodule identification (p=0.0001). No correlation was observed with the total number of cores in the series (p=0.37) or with prostate volume < or = 50 ml (p=0.87) or > 50 ml (p=0.09). In the multivariate analysis, age > 70 years (p=0.005), prostate volume < or = 50 ml (p=0.001), and ultrasound nodule identification (p=0.003) were identified as independent variables associated to cancer diagnosis. CONCLUSION: No statistically significant differences were found between the two prostate biopsy schemes. In glands over 50 ml in size, the sextant scheme may prove to be insufficient. PMID- 20354276 TI - Expression of matrix metalloproteinase-9 in prostate cancer. Preliminary experience. AB - OBJECTIVES: To study the validity of Matrix Metalloproteinase 9 as a complementary marker to PSA for the diagnosis and prognosis of Prostate Cancer. METHODS: Prospective study structured as a hospital-based cohort of 100 consecutive patients undergoing prostate biopsy. Serum determination of MMP-9 was carried out by means of inmunoassay. Statistical analysis was performed using the Stata/SE 8.2 software. RESULTS: 32 patients were diagnosed with prostate cancer and 52% had a Gleason score equal to or greater than 7. The values of serum MMP-9 varied between 225.7 and 1932.3 ng/ml, without significant differences among patients with benign, malignant and uncertain histology (p=0.429). The differences approached statistical significance in the subgroup of patients with PSA at 4-10 ng/ml (p=0.058), and significant differences were observed in the subgroup with free PSA to total PSA coefficient of less than 15% (p=0.037). No relationship between the Gleason score and the level of MMP-9 was shown (p=0.739). The levels of PSA and MMP-9 were shown to be independent (Pearson coefficient of correlation -0.1). CONCLUSIONS: It was not possible to show the efficacy of MMP-9 in predicting the result of the biopsy. In the group of patients with slightly increased levels of PSA (between 4 and 10 ng/ml) all the descriptive variables were higher in the group with malignant histology, though they did not reach statistical significance, they did reach significance when the coefficient of free PSA over total PSA was less than 15%, but this finding is not relevant clinically, as these patients already have a clear indication for biopsy. Neither was the relationship with the prognosis shown as there are no differences of MMP-9 expression at varying Gleason scores. PMID- 20354277 TI - Matrix metalloproteinase- 9 polymorphisms in the diagnosis of prostate cancer. A preliminary experience. AB - Polymorphisms Q279R, P574R and -1562 C/T of matrix metalloproteinase-9 (MMP-9) gene have been linked with the risk of cancer and with tumoral aggressiveness in various types of cancer. So far there are no studies in the literature analysing the link between polymorphisms Q279R, P574R and -1562 C/T of MMP-9 and prostate cancer. OBJECTIVES: To establish the presence of the MMP-9's gene polymorphisms (Q279R, P574R and -1562 C/T)in relation to results of prostate biopsy, PSA values and Gleason score. METHODS: Hospital cohort of 100 patients with suspected prostate cancer, subjected to prostate biopsy, in whom the MMP-9 polymorphisms (Q279R, P574R and -1562 C/T) were analysed using the PCR-RLFP technique. RESULTS: No statistically significant differences were found in the presence of the Q279R, P574R and -1562 C/T polymorphisms in terms of prostate biopsy results (p = 0.264, p = 0.406, p = 0.860, respectively), or Gleason score (p = 0.373, p = 0.367, p = 0.476). Comparing the genotypes of the Q279R, P574R and -1562 C/T polymorphisms resulting from prostate biopsy, using subgroups according to PSA values, no statistically significant differences were found either (p = 0.332 y p = 0.393, respectively ). However, statistically significant differences were found when comparing the genotypes of the -1562 C/T polymorphism of the MMP-9 in patients showing positive biopsy for malignant tumour in comparison to a negative biopsy for a malignant tumour in the subgroup of patients with PSA 10 ng/ml (p=0.049). The joint analysis of the three MMP-9 polymorphisms, using logistical regression study did not reveal any statistically significant differences as far as the risk of developing prostate cancer is concerned based on the presence of the Q279R, P574R and -1562 C/T polymorphisms. CONCLUSION: The Q279R, P574R and -1562 C/T polymorphisms are not linked with the aggressiveness in prostate cancer, neither they are linked to the risk of suffering prostate cancer. PMID- 20354278 TI - Sperm count. Do we need a new reference value? AB - OBJECTIVES: To evaluate the sperm count in fertile men, general population, and infertile men in different regions of the world. METHODS: Sperm counts were recorded according to their fertility status, proven fertility, men recruited from an andrology/infertility clinic, or healthy men. RESULTS: The average of sperm count in the different studies is lower in infertile men that in fertile men (p>0.001) and in the general population (p>0.001). CONCLUSION: Based on this analysis the normal sperm count is about 65 million per mL. Using these reference value, only the 25% of the studies in infertile men are above this value, and the 75% studies with fertile men (>65 x 106 sperm/mL). PMID- 20354280 TI - Measurement of scattered radiation in a volumetric 64-slice CT scanner using three experimental techniques. AB - Compton scatter poses a significant threat to volumetric x-ray computed tomography, bringing cupping and streak artefacts thus impacting qualitative and quantitative imaging procedures. To perform appropriate scatter compensation, it is necessary to estimate the magnitude and spatial distribution of x-ray scatter. The aim of this study is to compare three experimental methods for measurement of the scattered radiation profile in a 64-slice CT scanner. The explored techniques involve the use of collimator shadow, a single blocker (a lead bar that suppresses the primary radiation) and an array blocker. The latter was recently proposed and validated by our group. The collimator shadow technique was used as reference for comparison since it established itself as the most accurate experimental procedure available today. The mean relative error of measurements in all tube voltages was 3.9 +/- 5.5% (with a maximum value of 20%) for the single blocker method whereas it was 1.4 +/- 1.1% (with a maximum value of 5%) for the proposed blocker array method. The calculated scatter-to-primary ratio (SPR) using the blocker array method for the tube voltages of 140 kVp and 80 kVp was 0.148 and 1.034, respectively. For a larger polypropylene phantom, the maximum SPR achieved was 0.803 and 6.458 at 140 kVp and 80 kVp, respectively. Although the three compared methods present a reasonable accuracy for calculation of the scattered profile in the region corresponding to the object, the collimator shadow method is by far the most accurate empirical technique. Nevertheless, the blocker array method is relatively straightforward for scatter estimation providing minor additional radiation exposure to the patient. PMID- 20354279 TI - Ultrasound-based relative elastic modulus imaging for visualizing thermal ablation zones in a porcine model. AB - The feasibility of using ultrasound-based elastic modulus imaging to visualize thermal ablation zones in an in vivo porcine model is reported. Elastic modulus images of soft tissues are estimated as an inverse optimization problem. Ultrasonically measured displacement data are utilized as inputs to determine an elastic modulus distribution that provides the best match to this displacement field. A total of 14 in vivo thermal ablation zones were investigated in this study. To determine the accuracy of delineation of each thermal ablation zone using elastic modulus imaging, the dimensions (lengths of long and short axes) and the area of each thermal ablation zone obtained from an elastic modulus image were compared to the corresponding gross pathology photograph of the same ablation zone. Comparison of elastic modulus imaging measurements and gross pathology measurements showed high correlation with respect to the area of thermal ablation zones (Pearson coefficient = 0.950 and p < 0.0001). The radiological-pathological correlation was slightly lower (correlation = 0.853, p < 0.0001) for strain imaging among these 14 in vivo ablation zones. We also found that, on average, elastic modulus imaging can more accurately depict thermal ablation zones, when compared to strain imaging (14.7% versus 22.3% absolute percent error in area measurements, respectively). Furthermore, elastic modulus imaging also provides higher (more than a factor of 2) contrast-to-noise ratios for evaluating these thermal ablation zones than those on corresponding strain images, thereby reducing inter-observer variability. Our preliminary results suggest that elastic modulus imaging might potentially enhance the ability to visualize thermal ablation zones, thereby improving assessment of ablative therapies. PMID- 20354281 TI - Fluence-to-dose conversion coefficients for heavy ions calculated using the PHITS code and the ICRP/ICRU adult reference computational phantoms. AB - The fluence to organ-absorbed-dose and effective-dose conversion coefficients for heavy ions with atomic numbers up to 28 and energies from 1 MeV/nucleon to 100 GeV/nucleon were calculated using the PHITS code coupled to the ICRP/ICRU adult reference computational phantoms, following the instruction given in ICRP Publication 103 (2007 (Oxford: Pergamon)). The conversion coefficients for effective dose equivalents derived using the radiation quality factors of both Q(L) and Q(y) relationships were also estimated, utilizing the functions for calculating the probability densities of absorbed dose in terms of LET (L) and lineal energy (y), respectively, implemented in PHITS. The calculation results indicate that the effective dose can generally give a conservative estimation of the effective dose equivalent for heavy-ion exposure, although it is occasionally too conservative especially for high-energy lighter-ion irradiations. It is also found from the calculation that the conversion coefficients for the Q(y)-based effective dose equivalents are generally smaller than the corresponding Q(L) based values because of the conceptual difference between LET and y as well as the numerical incompatibility between the Q(L) and Q(y) relationships. The calculated data of these dose conversion coefficients are very useful for the dose estimation of astronauts due to cosmic-ray exposure. PMID- 20354282 TI - The potential for mixed multiplexed and non-multiplexed data to improve the reconstruction quality of a multi-slit-slat collimator SPECT system. AB - Multiplexing is a way of increasing the sensitivity in a multi-slit-slat SPECT system by allowing the overlap of projections from neighboring apertures. The fundamental objective of multiplexing is to increase the signal-to-noise ratio for a given system resolution. Multiplexing may therefore lead to an improved tradeoff between resolution and sensitivity. Overlapped projections, however, introduce ambiguities in the data which can lead to non-uniqueness of solution for the inverse problem, deterioration in the quality of reconstruction and ultimately loss of resolution. Therefore, it is not straightforward to evaluate the advantage of the extra sensitivity gained by multiplexing, without first devising a method to overcome the image artifacts caused due to this overlapping of projection data. In this paper we investigate the effect of multiplexing on the reconstructed image quality and we determine whether reconstruction of multiplexed data could be improved by the addition of non-multiplexed data. For this purpose we have done simulations based on three digital phantoms. We compared the reconstructed images both qualitatively and quantitatively for different degrees of multiplexing and different fractions of non-multiplexed data. Our results indicate that the recovery coefficient (and therefore spatial resolution) can be maintained with a high degree of multiplexing leading to a significant increase in the SNR (up to 25%) due to a reduced noise level. This gain in the SNR corresponds to a 75% increase in counts or sensitivity which can be utilized to reduce acquisition time, patient dose or/and improve image quality. PMID- 20354283 TI - A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy. AB - Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were delineated on each CT. The benefit of margin reduction to compensate for both rotation and deformation in the hybrid strategy was evaluated geometrically. With the hybrid strategy, the planning margins can be reduced by 1.4 mm for LRP, and 2.0 mm for IRP, compared with the standard online IGRT only, to maintain the same 99% target volume coverage. The average relative reduction in planning target volume (PTV) based on the internal target volume (ITV) from PTV based on CTV is 19% for LRP, and 27% for IRP. PMID- 20354284 TI - Dosimetry of stereotactic radiosurgery using lithium formate EPR dosimeters. AB - Small lithium formate EPR (electron paramagnetic resonance) dosimeters (diameter 3 mm, height 2 mm) were produced and employed for 2D dosimetry of stereotactic radiosurgery (SRS). An anthropomorphic head phantom with an in-house made insert holding 45 lithium formate dosimeters was used. A spherical target was outlined centrally in planning CT images of the head and an SRS dose plan with three arcs was made using the iPlan planning system. Beam collimation was achieved with the BrainLAB m3 micro-MLC. The minimum target dose was 15 Gy. The planned dose distribution was compared to measurements. For dosimetry, a dosimeter calibration series was generated with doses from 1 to 20 Gy. At the treatment unit, three replicate measurement series were performed. The measurements gave on average 2.2% lower dose at the plateau of the dose distribution compared to the dose plan. Larger differences were seen in the penumbra, where the dose plan underestimated the dose gradients. By repeated measurements, the systematic and random error in the SRS delivery was estimated to less than 1 mm. In conclusion, the planning system produced an intracranial dose distribution with tolerable accuracy. Furthermore, small lithium formate EPR dosimeters were useful for measuring SRS dose distributions. PMID- 20354286 TI - The triple pyrophosphate Cs3CaFe(P2O7)2. AB - The complex phosphate tricaesium calcium iron bis(diphosphate), Cs(3)CaFe(P(2)O(7))(2), has been prepared by the flux method. Isolated [FeO(5)] and [CaO(6)] polyhedra are linked by two types of P(2)O(7) groups into a three dimensional framework. The latter is penetrated by hexagonal channels along the a axis where three Cs atoms are located. Calculations of caesium Voronoi-Dirichlet polyhedra give coordination schemes for the three Cs atoms as [8 + 3], [9 + 1] and [9 + 4]. The structure includes features of both two- and three-dimensional frameworks of caesium double pyrophosphates. PMID- 20354288 TI - Octahedral distortion caused by hydrogen bonding in tris(diethylammonium) hexachloridoantimonate(III). AB - The factors influencing the distortion of inorganic anions in the structures of chloridoantimonates(III) with organic cations, in spite of numerous structural studies on those compounds, have not been clearly described and separated. The title compound, [(C(2)H(5))(2)NH(2)](3)[SbCl(6)], consisting of isolated distorted [SbCl(6)](3-) octahedra that have C(3) symmetry and [(C(2)H(5))(2)NH(2)](+) cations, unequivocally shows the role played by hydrogen bonding in the geometry variations of inorganic anions. The organic cations, which are linked to the inorganic substructure through N-H...Cl hydrogen bonds, are clearly responsible for the distortion of the octahedral coordination of Sb(III) in terms of differences (Delta) in both Sb-Cl bond lengths [Delta = 0.4667 (6) A] and Cl-Sb-Cl angles [Delta = 9.651 (17) degrees]. PMID- 20354287 TI - Substitutional and positional disorder in Sr(2.88)Cu(3.12)(PO4)4. AB - The title compound, a hydrothermally synthesized strontium copper(II) phosphate(V) (2.88/3.12/4), is isotypic with Sr(3)Cu(3)(PO(4))(4), obtained previously by solid-state reaction, but not with Sr(3)Cu(3)(PO(4))(4), obtained previously by the hydrothermal method. A surplus of copper was observed by both structural and chemical analysis, and the formula obtained by the structural analysis is in full agreement with results of the EDX (energy-dispersive X-ray diffraction) analysis. The structure consists of layers of Cu(3)O(12) groups which are linked via the PO(4) tetrahedra. The Cu(3)O(12) groups are formed by one Cu1O(4) and two Cu2O(5) coordination polyhedra sharing corners. The central Cu1 atom of the Cu(3)O(12) group is located at an inversion centre (special position 2a). The unique structural feature of the title compound is the presence of 12% Cu in the Sr1 site (special position 2b, site symmetry 1). Moreover, disordered Sr2 atoms were observed: a main site (Sr2a, 90%) and a less occupied site (Sr2b, 10%) are displaced by 0.48 (3) A along the b axis. Such substitutional and positional disorder was not observed previously in similar compounds. PMID- 20354289 TI - Tris(1,10-phenanthroline-kappa2N,N')cadmium(II) bis(perchlorate) 3.5-hydrate: a water chain stabilized by perchlorate anions. AB - The title compound, [Cd(C(12)H(8)N(2))(3)](ClO(4))(2).3.5H(2)O, contains a cross shaped one-dimensional channel along the c axis which encapsulates an ordered water chain. This water chain features a centrosymmetric cyclic water hexamer unit with a chair-like conformation. Neighbouring hexamers are linked by bridging water molecules. The host perchlorate anions recognize and stabilize the guest water chain via three kinds of hydrogen-bond patterns, leading to the formation of a complex one-dimensional {[(H(2)O)(7)(ClO(4))(4)](4-)}(n) anionic chain. One perchlorate acts as a single hydrogen-bond acceptor dangling on the chain, the second perchlorate on the chain serves as a double hydrogen-bond acceptor for only one water molecule to form an R(2)(2)(6) ring, where both entities lie on a twofold axis, while the third perchlorate, which also lies on a twofold axis, accepts two hydrogen bonds from two equivalent water molecules and is involved in the construction of an R(6)(5)(14) ring. PMID- 20354290 TI - Orientational disorder in Lambda-cobalt(III) sepulchrate trinitrate. AB - The crystal structure of Lambda-(1,3,6,8,10,13,16,19 octaazabicyclo[6.6.6]eicosane)cobalt(III) trinitrate, [Co(C(12)H(30)N(8))](NO(3))(3), consists of a sepulchrate moiety that serves as a macrobicyclic nitrogen cage for the Co(3+) cation, which is six-coordinated by N atoms, and three nitrate anions. The Co-sepulchrate group lies on a threefold axis (site symmetry 32), as do two symmetry-related and ordered nitrate groups (site symmetry 3), with which it is connected via N-H...O hydrogen bonds [Co-N = 5.1452 (12) A]. The third nitrate group is disordered as a result of symmetry requirements around the origin (site symmetry 32), and is further away from the Co-sepulchrate cage [Co-N = 6.3160 (8) A]. The structure is described by applying orientational disorder over six equivalent orientations for the disordered nitrate group, which is considered as an ideal planar molecule of regular trigonal geometry with its molecular plane rotated out of the ab plane and the molecular centre of gravity slightly shifted away from the origin. This new model for disorder clearly improves a previous crystal structure determination. PMID- 20354291 TI - Poly[[tetraaqua(mu7-pyridine-2,3,5,6-tetracarboxylato)dicadmium(II)] monohydrate]. AB - The title compound, {[Cd(2)(C(9)HNO(8))(H(2)O)(4)].H(2)O}(n), consists of two crystallographically independent Cd(II) cations, one tetrabasic pyridine-2,3,5,6 tetracarboxylate (pdtc) anion, four coordinated water molecules and one solvent water molecule. The Cd(II) cations have distorted square-antiprismatic (one pyridine N, six carboxylate O and one water O atom) and octahedral (three carboxylate O and three water O atoms) coordination environments. Each pdtc ligand employs its pyridine and carboxylate groups to chelate and bridge seven Cd(II) cations. The square-antiprismatic coordinated Cd(II) cations are linked by pdtc ligands into a lamellar framework structure, while the octahedral coordinated Cd(II) cations are bridged by the mu(2)-carboxylate O atoms and the pdtc ligands into a chain network that further joins neighbouring lamellae into a three-dimensional porous network. The cavities are filled with solvent water molecules that are linked to the host through complex hydrogen bonding. PMID- 20354292 TI - Copper(II) chloride and bromide complexes with 2-methyl-2H-tetrazol-5-amine: an X ray powder diffraction study. AB - The complex catena-poly[[dibromidocopper(II)]-bis(mu-2-methyl-2H-tetrazol-5 amine)-kappa(2)N(4):N(5);kappa(2)N(5):N(4)], [CuBr(2)(C(2)H(5)N(5))(2)](n), (I), and the isotypic chloride complex catena-poly[[dichloridocopper(II)]-bis(mu-2 methyl-2H-tetrazol-5-amine)-kappa(2)N(4):N(5);kappa(2)N(5):N(4)], [CuCl(2)(C(2)H(5)N(5))(2)](n), (II), were investigated by X-ray powder diffraction at room temperature. The crystal structure of (I) was solved by direct methods, while the Rietveld refinement of (II) started from the atomic coordinates of (I). In both structures, the Cu atoms lie on inversion centres, adopting a distorted octahedral coordination of two halogen atoms, two tetrazole N atoms and two 5-amine group N atoms. Rather long Cu-N(amine) bonds allow consideration of the amine group as semi-coordinated. The compounds are one dimensional coordination polymers, formed as a result of 2-methyl-2H-tetrazol-5 amine ligands bridging via a tetrazole N atom and the amine N atom. In the polymeric chains, adjacent Cu atoms are connected by two such bridges. PMID- 20354293 TI - An unusual polycatenating network self-assembled by the 2D --> 2D parallel --> 3D parallel interpenetration of coordinative and hydrogen-bonded (6,3) motifs. AB - In the title coordination compound, catena-poly[[[bis[diaquacadmium(II)]-mu(2) trans-1,2-bis(4-pyridyl)ethene]bis{mu(2)-2,2'-[(5-carboxymethoxy-m phenylene)dioxy]diacetato}] trans-1,2-bis(4-pyridyl)ethene solvate dihydrate], {[Cd(2)(C(12)H(10)O(9))(2)(C(12)H(10)N(2))(H(2)O)(4)].C(12)H(10)N(2).2H(2)O}(n), (I), each Cd(II) centre adopts a pentagonal-bipyramidal coordination geometry. The incompletely deprotonated 2,2'-[(5-carboxymethoxy-m-phenylene)dioxy]diacetate (TCMB) ligands and trans-1,2-bis(4-pyridyl)ethene (bpe) ligands both act as bidentate bridges, linking the Cd(II) centres into one-dimensional ladders, which are connected into an undulating two-dimensional (6,3) layer through O-H...N hydrogen bonds between the carboxylate groups of the TCMB ligands and the N atoms of the uncoordinated bpe ligands. Each undulating layer polycatenates two other identical layers, exhibiting the unusual combination of both 2D --> 2D parallel and 2D --> 3D parallel interpenetration (2D and 3D are two- and three dimensional, respectively). PMID- 20354294 TI - Zoledronate complexes. II. catena-Poly[[tetraaquabis[hemihydrogen mu3-1-hydroxy-2 (imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato-kappa3O:O':O'']bis[mu3-1 hydroxy-2-(imidazol-3-ium-1-yl)ethylidene-1,1-diphosphonato kappa4O:O,O':O'']trisodium] dihydrate]. AB - The title compound, {[Na(3)(C(5)H(9)N(2)O(7)P(2))(2)(C(5)H(9.5)N(2)O(7)P(2))(2)(H(2)O)(4)].2H(2)O}(n) (II), is polymeric and consists of undulating chains parallel to [011] interconnected by hydrogen-bonding and pi-pi interactions. There are two independent Na(+) cations in the asymmetric unit (one lying on an inversion centre), two zoledronate anions and three water molecules, two of which are coordinated and one of which is a free solvate. Each cation is surrounded in an octahedral fashion by O atoms from four different zoledronate units and two/one coordinated water molecules. The zoledronate groups present their usual zwitterionic character, with negative charges in the protonated phosphonates and a positive charge at the protonated imidazole N atom. Two symmetry-related phosphonate groups share (in the form of a very strong linear hydrogen bond) an H atom lying on a symmetry centre, midway between the O atoms involved. The zoledronate binding modes present in (II) are both unreported for bisphosphonate anions. Intra- and inter-chain interactions are enhanced by a variety of hydrogen bonds where all the available O-H and N-H donors are involved, in addition to a strong imidazole-phosphonate C-H...O interaction, typical in these kinds of structures. PMID- 20354295 TI - Constructor graph description of the hydrogen-bonding supramolecular assembly in two ionic compounds: 2-(pyrazol-1-yl)ethylammonium chloride and diaquadichloridobis(2-hydroxyethylammonium)cobalt(II) dichloride. AB - Covalent bond tables are used to generate hydrogen-bond pattern designator symbols for the crystallographically characterized title compounds. 2-(Pyrazol-1 yl)ethylammonium chloride, C(5)H(10)N(3)(+).Cl(-), (I), has three unique, strong, charge-assisted hydrogen bonds of the types N-H...Cl and N-H...N that form unary through ternary levels of graph-set interactions. Diaquadichloridobis(2 hydroxyethylammonium)cobalt(II) dichloride, [CoCl(2)(C(2)H(8)NO)(2)(H(2)O)(2)]Cl(2), (II), forms five unique charge-assisted hydrogen bonds of the types O-H...Cl and N-H...Cl. These form graph-set patterns up to the quinary level. The Co complex in (II) resides at a crystallographic inversion center; thus the number of hydrogen bonds to consider doubles due to their G-equivalence, and the handling of such a case is demonstrated. PMID- 20354296 TI - Poly[[[aqua(2,2'-bipyridine-kappa2N,N')manganese(II)]-mu-croconato kappa4O,O':O'',O'''] monohydrate]: a one-dimensional coordination polymer connected by hydrophilic-hydrophilic and lipophilic-lipophilic interactions at 135 K. AB - In the title one-dimensional coordination polymer, {[Mn(C(5)O(5))(C(10)H(8)N(2))(H(2)O)].H(2)O}(n), each Mn(II) ion is seven coordinated by four O atoms from two croconate ligands, two N atoms from a 2,2' bipyridine (2,2'-bipy) ligand and one O atom from an aqua ligand. The croconate ligand bridges the Mn(II) ions in a bis-bidentate chelation mode, forming an extended [Mn(C(5)O(5))](n) chain running parallel to the [001] direction, with the lipophilic 2,2'-bipy ligands lying along one side and the hydrophilic water molecules along the opposite side. Coordinated water and solvent water molecules are arranged in the hydrophilic layer, which is characterized by O-H...O hydrogen bonds between croconate ligands. Meanwhile, 2,2'-bipy ligands from adjacent chains partially overlap and exhibit pi-pi interactions to form a lipophilic layer. The hydrophilic and lipophilic layers are arranged alternately to build a layer structure. PMID- 20354297 TI - An ice-like water hexamer with 3 symmetry in the hydrogen-bonded structure of 2,3,5,6-tetrafluoro-1,4-bis(imidazol-1-ylmethyl)benzene dihydrate. AB - An ice-like hexameric water cluster, stabilized by the flexible bis-imidazolyl compound 2,3,5,6-tetrafluoro-1,4-bis(imidazol-1-ylmethyl)benzene (Fbix), is found in the trigonal R3 crystal structure of the title compound, C(14)H(10)F(4)N(4).2H(2)O or Fbix.2H(2)O. The Fbix molecule lies about an inversion centre with one water molecule in the asymmetric unit in a general position. A cyclic chair-like hexameric water cluster with 3 symmetry is generated with a hydrogen-bonded O...O distance within the hexamer of 2.786 (3) A. The Fbix molecule adopts a trans conformation, where the imidazole ring makes a dihedral angle of 70.24 (11) degrees with the central tetrafluorinated aromatic ring. Each water hexamer is connected by six Fbix molecules through intermolecular O-H...N hydrogen bonds [N...O = 2.868 (3) A] to yield a three dimensional supramolecular network with primitive cubic (pcu) topology. Large voids in each single pcu network lead to fourfold interpenetrated aggregates of Fbix.2H(2)O. PMID- 20354298 TI - 2-Amino-4-(piperidin-1-yl)-11H-pyrimido[4,5-b][1,5]benzodiazepin-6-ium chloride monohydrate and 2-amino-4-[methyl(2-methylphenyl)amino]-11H-pyrimido[4,5 b][1,5]benzodiazepin-6-ium chloride-benzene-1,2-diamine (1/1): complex sheets generated by multiple hydrogen bonds. AB - In each of 2-amino-4-(piperidin-1-yl)-11H-pyrimido[4,5-b][1,5]benzodiazepin-6-ium chloride monohydrate, C(16)H(19)N(6)(+).Cl(-).H(2)O, (I), and 2-amino-4-[methyl(2 methylphenyl)amino]-11H-pyrimido[4,5-b][1,5]benzodiazepin-6-ium chloride-benzene 1,2-diamine (1/1), C(19)H(19)N(6)(+).Cl(-).C(6)H(8)N(2), (II), the seven-membered ring in the cation adopts a boat conformation. The pyrimidine ring in (II) adopts a twist-boat conformation, but the corresponding ring in (I) is essentially planar. The amino groups of the benzene-1,2-diamine component of (II) are both pyramidal. The independent components of (I) are linked into complex sheets by a combination of N-H...O, N-H...N, N-H...Cl and O-H...Cl hydrogen bonds. In the crystal structure of (II), one N-H...N hydrogen bond and six independent N-H...Cl hydrogen bonds combine to link the components into complex sheets. PMID- 20354299 TI - 5-Amino-1-benzoyl-3-methylpyrazole: complex sheets built from N-H...N, C-H...O and C-H...pi(arene) hydrogen bonds. AB - Molecules of the title compound [systematic name: (5-amino-3-methylpyrazol-1 yl)(phenyl)methanone], C(11)H(11)N(3)O, contain an intramolecular hydrogen bond. The molecules are linked into sheets by a combination of N-H...N, C-H...O and C H...pi(arene) hydrogen bonds. Comparisons are made with the hydrogen-bonded structures of some related compounds. PMID- 20354300 TI - A hydrogen-bonded dimer in 6-(4-bromophenyl)-3-methyl-1-phenyl-4,5-dihydro-1H pyrazolo[3,4-b]pyridine and a chain of rings built from N-H...N and C H...pi(pyridine) hydrogen bonds in 3-(4-nitrophenyl)-4-phenyl-1H-pyrazolo[3,4 b]pyridine. AB - In 6-(4-bromophenyl)-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridine, C(19)H(16)BrN(3), the reduced pyridine ring adopts a conformation that is close to a screw-boat form. Molecules are linked by pairs of symmetry-related C H...pi(arene) hydrogen bonds into cyclic centrosymmetric dimers. Molecules of 3 (4-nitrophenyl)-4-phenyl-1H-pyrazolo[3,4-b]pyridine, C(18)H(12)N(4)O(2), are linked into centrosymmetric R(2)(2)(8) dimers by pairs of symmetry-related N H...N hydrogen bonds, and these dimers are linked by pairs of C-H...pi(pyridine) hydrogen bonds to form a chain of edge-fused rings, or a molecular ladder, along [100]. The molecular aggregation in this compound is completed by two weak C H...O hydrogen bonds, one of which links the chains along [100] into sheets. PMID- 20354301 TI - Hydrogen-bonding patterns in three substituted N-benzyl-N-(3-tert-butyl-1-phenyl 1H-pyrazol-5-yl)acetamides. AB - The molecules of N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-2-chloro-N-(4 methoxybenzyl)acetamide, C(23)H(26)ClN(3)O(2), are linked into a chain of edge fused centrosymmetric rings by a combination of one C-H...O hydrogen bond and one C-H...pi(arene) hydrogen bond. In N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-2 chloro-N-(4-chlorobenzyl)acetamide, C(22)H(23)Cl(2)N(3)O, a combination of one C H...O hydrogen bond and two C-H...pi(arene) hydrogen bonds, which utilize different aryl rings as the acceptors, link the molecules into sheets. The molecules of S-[N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-N-(4 methylbenzyl)carbamoyl]methyl O-ethyl carbonodithioate, C(26)H(31)N(3)O(2)S(2), are also linked into sheets, now by a combination of two C-H...O hydrogen bonds, both of which utilize the amide O atom as the acceptor, and two C-H...pi(arene) hydrogen bonds, which utilize different aryl groups as the acceptors. PMID- 20354302 TI - Tri-tert-butyl 3-oxo-4-oxa-1,8,11-triazaspiro[5.6]dodecane-1,8,11-triacetate. AB - The title compound, C(26)H(45)N(3)O(8), is a bicyclic molecule; the seven membered diazepane ring has a twisted-chair conformation and the six-membered morpholine ring has a boat conformation. PMID- 20354303 TI - The 293 K structure of tetradehydrohaliclonacyclamine A. AB - The polycyclic title compound {systematic name: (1S,16S,17S,31S)-3,20 diazatetracyclo[15.15.0(1,17).1(3,31).1(16,20)]tetratriaconta-6,8,23,25 tetraene}, C(32)H(52)N(2), has recently been isolated and characterized structurally, in solution by NMR spectroscopy and in the solid state by X-ray crystallography. At 130 K the structure is monoclinic (P2(1), Z = 4) and comprises two molecules in the asymmetric unit with distinctly different conformations in the twelve-C-atom bridging chains. We report that, at 250 K, a phase change from monoclinic to orthorhombic (P22(1)2(1), Z = 4) occurs. The higher-temperature phase is structurally characterized herein at 293 K. The two different conformers resolved in the monoclinic low-temperature form merge to give a single disordered molecule in the asymmetric unit of the high-temperature phase. PMID- 20354304 TI - Three-dimensional supramolecular architecture in imidazolium hydrogen 2,3,5,6 tetrafluoroterephthalate. AB - The asymmetric unit of the title salt formed between 2,3,5,6 tetrafluoroterephthalic acid (H(2)tfbdc) and imidazolium (ImH), C(3)H(5)N(2)(+).C(8)HF(4)O(4)(-), contains one Htfbdc(-) anion and one ImH(2)(+) cation, joined by a classical N-H...O hydrogen bond. The acid and base subunits are further linked by N-H...O and O-H...O hydrogen bonds into infinite two dimensional layers with R(6)(5)(32) hydrogen-bond motifs. The resulting (4,4) network layers interpenetrate to produce an interlocked three-dimensional structure. The final three-dimensional supramolecular architecture is further stabilized by the linkages of two C-H...O interactions. PMID- 20354305 TI - C-H...pi interactions in cocrystals of bis(trimethylsilyl)acetylene and diphenylacetylene with benzene. AB - We present here the crystal structures of two acetylene derivatives cocrystallized with benzene, namely bis(trimethylsilyl)acetylene benzene solvate, C(8)H(18)Si(2).C(6)H(6), (I), and diphenylacetylene benzene solvate, C(14)H(10).C(6)H(6), (II). In (I), both molecules belong to the symmetry point group C(2h) and are located about special positions with site symmetry 2/m. In (II), both molecules show crystallographic inversion symmetry. In both structures, there are C-H...pi contacts between aromatic H atoms and the pi electrons of the triple bond. In addition to these, in (II) there are C-H...pi contacts between aromatic H atoms and the pi-electron cloud of the benzene molecules. PMID- 20354306 TI - 6beta-Methyl-B-norandrostenedione. AB - The title compound, C(19)H(26)O(2), a B-norandrogen with a 6beta-methyl group, is a recently identified and experimentally tested potent new aromatase inhibitor. It shares structural and physicochemical similarities both with the natural substrate of the enzyme, androstenedione, and with exemestane, another potent aromatase inhibitor having a 6-methylidene group. X-ray diffraction results indicate that the B-nor molecule and exemestane have nearly the same oxygen oxygen and methyl-methyl separations, though they have distinct configurations of the hydrophobic groups at the 6-position. These structural comparisons allow correlations to be inferred between the active site geometry of the molecules and the aromatase inhibition power of the studied compound. PMID- 20354307 TI - Crystallographic rationalization of the reactivity and spectroscopic properties of (2R)-S-(2,5-dihydroxyphenyl)cysteine. AB - At 150 K, the title compound, C(9)H(11)NO(4)S, crystallizes in the orthorhombic form as a zwitterion and has a low gauche conformation [chi = -46.23 (16) degrees] for an acyclic cysteine derivative. A difference in bond length is observed for the alkyl C-S bond [1.8299 (15) A] and the aryl C-S bond [1.7760 (15) A]. The -NH(3)(+) group is involved in four hydrogen bonds, two of which are intermolecular and two intramolecular. The compound forms an infinite three dimensional network constructed from four intermolecular hydrogen bonds. Characterization data ((13)C NMR, IR and optical rotation) are reported to supplement the incomplete data disclosed previously in the literature. PMID- 20354308 TI - 4-(3,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3,5-dimethyl-1H-pyrazol-2-ium dihydrogen phosphate: a combined X-ray and DFT study. AB - The molecular structure of the title salt, C(11)H(17)N(4)(+).H(2)PO(4)(-), has been determined from single-crystal X-ray analysis and compared with the structure calculated by density functional theory (DFT) at the BLYP level. The crystal packing in the title compound is stabilized primarily by intermolecular N H...O, O-H...N and O-H...O hydrogen bonds and pi-pi stacking interactions, and thus a three-dimensional supramolecular honeycomb network consisting of R(4)(2)(10), R(4)(4)(14) and R(4)(4)(24) ring motifs is established. The HOMO LUMO energy gap (1.338 eV; HOMO is the highest occupied molecular orbital and LUMO is the lowest unoccupied molecular orbital) indicates a high chemical reactivity for the title compound. PMID- 20354310 TI - A new polymorph of benzene-1,2-diamine: isomorphism with 2-aminophenol and two dimensional isostructurality of polymorphs. AB - A new crystalline form of benzene-1,2-diamine, C(6)H(8)N(2), crystallizing in the space group Pbca, has been identified during screening for cocrystals. The crystals are constructed from molecular bilayers parallel to (001) that have the polar amino groups directed to the inside and the aromatic groups, showing a herringbone arrangement, directed to the outside. The known monoclinic form and the new orthorhombic polymorph exhibit two-dimensional isostructurality as the crystals consist of nearly identical bilayers. In the monoclinic form, neighbouring bilayers are generated by a unit translation along the a axis, whereas in the orthorhombic form they are generated by a c-glide. Moreover, the new form of benzene-1,2-diamine is essentially isomorphous with the only known form of 2-aminophenol. PMID- 20354309 TI - 2-Amino-8-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)imidazo[1,2-a][1,3,5]triazin 4(8H)-one monohydrate, a 2'-deoxyguanosine analogue with an altered Watson-Crick recognition site. AB - The title compound, C(10)H(12)FN(5)O(4).H(2)O, shows an anti glycosyl orientation [chi = -123.1 (2) degrees]. The 2-deoxy-2-fluoroarabinofuranosyl moiety exhibits a major C2'-endo sugar puckering (S-type, C2'-endo-C1'-exo, (2)T(1)), with P = 156.9 (2) degrees and tau(m) = 36.8 (1) degrees , while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4'-C5' bond is -sc (trans, gauche), with gamma = -78.3 (2) degrees. Both nucleoside and solvent molecules participate in the formation of a three-dimensional hydrogen-bonding pattern via intermolecular N-H...O and O-H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding. PMID- 20354311 TI - Pentacoordination versus tetracoordination in silicon derivatives of an O,N,O' tridentate ligand. AB - Bis[2-(2-hydroxy-3-methoxybenzylideneamino)phenolato-kappaO]dimethylsilicon, C(30)H(30)N(2)O(6)Si, (II), was isolated from the reaction of 2-(2-hydroxy-3 methoxybenzylideneamino)phenol, (I), with dichlorodimethylsilane at 339 K. It consists of two ligand molecules and the Me(2)Si unit forming a dialkoxydimethylsilane with a tetracoordinate Si atom. [2-(3-Methoxy-2 oxidobenzylideneamino)phenolato-kappa(3)O,N,O']dimethylsilicon, C(16)H(17)NO(3)Si, (III), was isolated from the same reaction conducted at 263 K. In this complex, the dianion of (I) is coordinated via two O atoms and an azomethine N atom to the pentacoordinate Si atom. According to quantum chemical calculations, (II) is the thermodynamically stable product and (III) is the kinetically favoured product. PMID- 20354312 TI - A three-dimensional hydrogen-bonded framework in (2S*,4R*)-7-fluoro-2-exo-[(E) styryl]-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine. AB - Molecules of the title compound, C(18)H(16)FNO, are linked into a three dimensional framework structure by a combination of two C-H...O hydrogen bonds and three C-H...pi(arene) hydrogen bonds. Comparisons are made with the (2R,4R) diastereoisomer and with the corresponding pair of diastereoisomeric 7-chloro analogues. PMID- 20354313 TI - Hydrogen-bonded dimers, chains and rings in six differently substituted 2 vinyltetrahydro-1,4-epoxy-1-benzazepines. AB - In (2SR,4RS)-2-exo-vinyl-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(12)H(13)NO, (I), the molecules are linked by two independent C-H...pi(arene) hydrogen bonds to form sheets, such that all of the molecules in a given sheet are of the same configuration. The molecules of (2SR,4RS)-7-chloro-2-exo-(2 methylprop-1-enyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(14)H(16)ClNO, (II), are linked by a C-H...O hydrogen bond into C(4) chains, where all the molecules in a given chain are of the same configuration, whereas the molecules of (2SR,4RS)-8-chloro-9-methyl-2-exo-(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H 1,4-epoxy-1-benzazepine, C(15)H(18)ClNO, (III), are linked into centrosymmetric dimers by pairs of symmetry-related C-H...pi(arene) hydrogen bonds. (2RS,4RS)-8 Chloro-9-methyl-2-endo-(2-methylprop-1-enyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1 benzazepine, C(15)H(18)ClNO, (IV), is a diastereoisomer of (III) and, as for (II), a single C-H...O hydrogen bond links the molecules into C(4) chains, each containing molecules of a single configuration. The structure of (2SR,4RS)-8 chloro-9-methyl-2-exo-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1 benzazepine, C(14)H(16)ClNO, (V), contains a C-H...O hydrogen bond which links pairs of molecules into centrosymmetric R(2)(2)(6) dimers. (2SR,4RS)-7,9-Dichloro 2-exo-(prop-1-en-2-yl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(13)H(13)Cl(2)NO, (VI), is an inversion twin containing both the (2S,4R) and (2R,4S) enantiomers in the space group P2(1), and a C-H...O hydrogen bond links molecules of a given configuration into simple C(3) chains. PMID- 20354315 TI - Benzene-1,4-diboronic acid-4,4'-bipyridine-water (1/2/2). AB - In the presence of water, benzene-1,4-diboronic acid (1,4-bdba) and 4,4' bipyridine (4,4'-bpy) form a cocrystal of composition (1,4-bdba)(4,4' bpy)(2)(H(2)O)(2), in which the molecular components are organized in two, so far unknown, cyclophane-type hydrogen-bonding patterns. The asymmetric unit of the title compound, C(6)H(8)B(2)O(4).2C(10)H(8)N(2).2H(2)O, contains two 4,4'-bpy, two water molecules and two halves of 1,4-bdba molecules arranged around crystallographic inversion centers. The occurrence of O-H...O and O-H...N hydrogen bonds involving the water molecules and all O atoms of boronic acid gives rise to a two-dimensional hydrogen-bonded layer structure that develops parallel to the (01-4) plane. This supramolecular organization is reinforced by pi-pi interactions between symmetry-related 4,4'-bpy molecules. PMID- 20354314 TI - 1-(beta-D-Erythrofuranosyl)adenosine. AB - The title compound, also known as beta-erythroadenosine, C(9)H(11)N(5)O(3), (I), a derivative of beta-adenosine, (II), that lacks the C5' exocyclic hydroxymethyl (-CH(2)OH) substituent, crystallizes from hot ethanol with two independent molecules having different conformations, denoted (IA) and (IB). In (IA), the furanose conformation is (O)T(1)-E(1) (C1'-exo, east), with pseudorotational parameters P and tau(m) of 114.4 and 42 degrees, respectively. In contrast, the P and tau(m) values are 170.1 and 46 degrees, respectively, in (IB), consistent with a (2)E-(2)T(3) (C2'-endo, south) conformation. The N-glycoside conformation is syn (+sc) in (IA) and anti (-ac) in (IB). The crystal structure, determined to a resolution of 2.0 A, of a cocrystal of (I) bound to the enzyme 5' fluorodeoxyadenosine synthase from Streptomyces cattleya shows the furanose ring in a near-ideal (O)E (east) conformation (P = 90 degrees and tau(m) = 42 degrees) and the base in an anti (-ac) conformation. PMID- 20354316 TI - Unexpected conformational consequences of weak hydrogen bonds on 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.1(3,7).1(9,13).1(15,19)]octacosane monohydrate. AB - In the title compound, C(20)H(40)N(8).H(2)O, the organic molecule crystallizes with one water molecule located within the molecular cavity of the octaaza macrocycle. The two molecules are linked via two weak O-H...N hydrogen bonds. The assembly has noncrystallographic C(2) axial symmetry. PMID- 20354317 TI - Hydrogen-bonded networks in 5-chloropyridin-2-amine-fumaric acid (2/1) and 2 aminopyridinium DL-malate. AB - Crystals of 5-chloropyridin-2-amine-(2E)-but-2-enedioate (2/1), 2C(5)H(5)ClN(2).C(4)H(4)O(4), (I), and 2-aminopyridinium DL-3-carboxy-2 hydroxypropanoate, C(5)H(7)N(2)(+).C(4)H(5)O(5)(-), (II), are built from the neutral 5-chloropyridin-2-amine molecule and fumaric acid in the case of (I) and from ring-N-protonated 2-aminopyridinium cations and malate anions in (II). The fumaric acid molecule lies on an inversion centre. In (I), the neutral 5 chloropyridin-2-amine and fumaric acid molecules interact via hydrogen bonds, forming two-dimensional layers parallel to the (100) plane, whereas in (II), oppositely charged units interact via ionic and hydrogen bonds, forming a three dimensional network. PMID- 20354318 TI - Hydrogen-bonding controls the solid-state and enantiomeric conformations of the amino alcohol ligand 2-[(2-hydroxyethyl)amino]cyclohexanol. AB - The crystal structure of the title compound, C(8)H(17)NO(2), consists of (R,R) and (S,S) enantiomeric pairs packed in adjacent double layers which are characterized by centrosymmetric hydrogen-bonded dimers, generated via N-H...O and O-H...O interactions, respectively. Intermolecular interactions, related to acceptor and donor molecule chirality, link the achiral double layers into tubular columns, which consist of a staggered hydrophilic inner core surrounded by a hydrophobic cycloalkyl outer surface and extend in the [011] direction. PMID- 20354319 TI - Five 2-aryl-substituted tetrahydro-1,4-epoxy-1-benzazepines: isolated molecules and hydrogen-bonded chains and sheets. AB - (2SR,4RS)-2-exo-Phenyl-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(16)H(15)NO, (I), (2SR,4RS)-2-exo-(4-chlorophenyl)-2,3,4,5-tetrahydro-1H-1,4 epoxy-1-benzazepine, C(16)H(14)ClNO, (II), and (2SR,4RS)-2-exo-(3-methylphenyl) 2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(17)H(17)NO, (III), all crystallize with Z' = 2, in the space groups Cc, P2(1)/n and P2(1)/c, respectively. In each of (II) and (III), the conformations of the two independent molecules are significantly different. The molecules in (I) are linked by C H...pi(arene) hydrogen bonds to form two independent chains, each containing only one type of molecule. The molecules in (II) are linked into sheets by a combination of C-H...O, C-H...(N,O) and C-H...pi(arene) hydrogen bonds, all of which link pairs of molecules related by inversion, while in (III), the molecules are linked into sheets by a combination of C-H...N, C-H...O and C-H...pi(arene) hydrogen bonds. There are no direction-specific intermolecular interactions of any kind in the structure of (2SR,4RS)-7-bromo-2-exo-phenyl-2,3,4,5-tetrahydro-1H 1,4-epoxy-1-benzazepine, C(16)H(14)BrNO, (IV), but in the structure of (2SR,4RS) 2-exo-(4-bromophenyl)-7-chloro-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(16)H(13)BrClNO, (V), a combination of one C-H...N hydrogen bond and one C-H...O hydrogen bond links the molecules into sheets of alternating centrosymmetric R(2)(2)(14) and R(6)(6)(22) rings. Comparisons are made with the structures of a number of related compounds. PMID- 20354320 TI - [Musculoskeletal rehabilitation and bone. Musculoskeletal atrophy, and rehabilitation medicine]. AB - Weightless environments such as prolonged bed rest and spaceflight are associated with dramatic losses of muscle volume and bone mass that hinder patients' or astronauts' health and reintegration into daily life. It is important that the countermeasure is effective for slow twitch fiber, and adds mechanical stress to a bone. So, we developed the hybrid training method (HYB) as a countermeasure of this musculoskeletal atrophy, which uses the contraction produced in a muscle by electrical stimulation of antagonist to resist the volitional contraction of agonist. HYB has several features. These include ; 1) simple device, 2) simultaneous contractions both agonist and antagonist musculature, 3) volitional contraction of deep layers of muscle, 4) longitudinal bone force loads. Several studies reported that, this HYB was tested successfully for increasing muscles strength and hypertrophy in the upper and lower extremities. And, a wearable HYB apparatus with a virtual reality control system was developed. Now, we are developing the hybrid ergometer with virtual reality system, which training can play while playing a game at home. PMID- 20354321 TI - [Musculoskeletal rehabilitation and bone. Influence of medicines and hormones on musculoskeletal rehabilitation]. AB - Declined anabolic and gonadal steroid hormones with age affect the development of age-related musculoskeletal disorders, including osteoporosis and sarcopenia. Exercises could have an influence on hormones affecting bone and muscle metabolism. Studies have shown that a combination of physical exercise and hormone replacement therapy (HRT) has a significantly better effect on bone and muscle than either of these interventions alone. Recent studies provide possible mechanisms for HRT effects in augmenting skeletal muscle repair and retention of muscle mass in older woman. Vitamin D improves musculoskeletal functions and prevents falls. However, it is not known whether exercise and bisphosphonates are able to interact in improving musculoskeletal functions. PMID- 20354322 TI - [Musculoskeletal rehabilitation and bone. Prevention of fall-related fractures in elderly]. AB - Fall-related fracture in elderly is one of the big issues in our aging society. A major cause of fractures in elderly is fall. Therefore, the prevention of falls is essential for the prevention of fractures in elderly. Various risk factors of falls such as physical fragility, cognitive decline and visual problem have been reported. The effective way for prevention of falls is the modification of the risk factors for falls. Especially, exercise has been known effective. In addition to prevention of falls, we should explore the appropriate approach to modify fall direction, defensive reaction, local shock absorption, which are closely related to fall-related fracture risk. PMID- 20354323 TI - [Musculoskeletal rehabilitation and bone. Mechanical stress on the skeletal system]. AB - Mechanical stress is one of the most important physiological factors for maintaining bone mass. Mechanical unloading leads to both reduced formation and enhanced resorption of bone, which is called "uncoupling" , causing immobilization osteoporosis. On the other hand, aging and excess mechanical stress causes damage and degeneration of articular cartilage, leading to osteoarthritis. Mechanical stress is sensed by osteocytes embedded in the bone tissue and probably by other cells as well. However, the mechanoreceptor in bone is yet to be molecularly identified, and downstream signaling events are not completely understood. This review will briefly summarize our knowledge on the mechanical stress-induced signaling pathways and relevant diseases. PMID- 20354324 TI - [Musculoskeletal rehabilitation and bone. A novel approach to mechanotransduction using cell-adhesion-patterned cells]. AB - Human vascular endothelial cells form the interface between the bloodstream and vessel walls and are continuously subjected to mechanical stimulation. When endothelial cells are stretched cyclically, along one axis, they align perpendicular to the axis of stretch. We previously reported that applying a cyclic, uni-axial strain to cells induced tyrosine phosphorylation of focal adhesion kinase and stimulated mitogen-activated protein kinase. However, it is difficult to quantify and analyze the spatial distribution of tyrosine phosphorylation in these cells, as they form focal adhesions randomly. Recently, we developed a system to overcome this problem by preparing individual, uniform, patterned cells that could be stretched cyclically and uni-axially. In this system we were able to statistically analyze cellular responses in these patterned cells, when subjected to a cyclic, uni-axial strain, using fluorescent microscopy. PMID- 20354325 TI - [Musculoskeletal rehabilitation and bone. Mechanical stress and bone quality : do mechanical stimuli alter collagen cross-link formation in bone? "Yes" ]. AB - Evidence has accumulated that collagen cross-links also play important roles in bone strength and the proper biological functions of bone. Thus, collagen cross links may be a factor in determining the material properties of bone. Collagen cross-linking is affected by some growth factors, and tissue age. Collagen cross links can be roughly divided into two types : lysyl oxidase mediated cross-links (enzymatic immature, divalent and mature, trivalent cross-links) and advanced glycation end-products (AGE ; non-enzymatic, pentosidine cross-links). These two types vary by both the mechanism of formation and by functional differences. Hyper- and micro-gravity, weight-bearing, and low intensity pulsed ultrasound (LIPUS) have distinct biological effects on bone collagen cross-link formation in vitro and in vivo (Saito M, J Bone Miner Res 2003, Bone 2004, Calcif Tissue Int 2004) . We demonstrated in previous studies that physiologic levels of mechanical strain such as hypergravity, weight-bearing, and LIPUS induce the formation of bone-type collagenous matrix into a specific molecular packing arrangement through the formation of characteristic types of cross-links as mineralization begins. Collagen cross-links play important roles in the expression of bone strength and the proper biological function of bone. Thus, collagen cross-links are thought to be a determinant of bone quality. While LIPUS have beneficial effects on collagen enzymatic cross-link formation, mechanical stress may improve bone quality (Saito M, Osteoporos Int, REVIEW, 2010) . PMID- 20354326 TI - [Musculoskeletal rehabilitation and bone. locomotive syndrome]. AB - In accordance with the increase of elderly population in Japan, the number of the elderly requiring care services is also increasing. Musculoskeletal conditions account for 24% of the causes for requiring care services. These backgrounds lead to the advocacy of the term "Locomotive Syndrome" by the Japanese Orthopaedic Association in 2007. This means such conditions that an elderly person necessitates or is at risk of necessitating care services due to the decreased ambulation caused mainly by aging-related musculoskeletal disorders, and judged with seven check items at this point of time. This syndrome requires intervention with exercise training, and two kinds of "Locomotion Trainings" are recommended as easily performable ones at home. PMID- 20354327 TI - [Musculoskeletal rehabilitation and bone. Musculoskeletal response to human space flight and physical countermeasures]. AB - The assembly of the Japanese Experiment Module "Kibo" to international space station was completed in 2009 and Koichi Wakata became the first Japanese station astronaut who spent more than 4 months in the station. Bone and muscle losses are significant medical concerns for long duration human space flight. Effective countermeasure program for bone loss and muscle atrophy is necessary to avoid post flight bone fracture and joint sprain after landing. The musculoskeletal response to human space flight and current physical countermeasure program for station astronauts are described. PMID- 20354328 TI - [Musculoskeletal rehabilitation and bone. Abnormal bone metabolism in female elite athletes]. AB - Recently, female athletes are particularly well, the other hand, many athletes suffer from amenorrhea due to excessive training. Especially, in sports with weight restrictions, they suffer from "Female athlete triad" , eating disorders, amenorrhea and osteoporosis. Amenorrhea is nothing else than a lack of estrogen, action on bone resorption and promote bone formation, by neglect this, it lead to osteoporosis and a stress fracture, and they would often give up their career as elite athletes. So we should consider it as serious sports injury. The problems of amenorrhea is should be recognized as a deficiency of estrogen. A Case of amenorrhea in female athletes, it is necessary to consider the hormone replacement therapy based on the appropriate diagnosis. However, it is important to start the management of body fat and body weight and strength of exercises since adolescent for the prevention the amenorrhea. PMID- 20354329 TI - [Musculoskeletal rehabilitation and bone. Development of Simulator (Jouba) for horse riding therapy and utility for the aged]. AB - Horseback riding therapy is popularly used as one of the physiotherapy in Europe. Dr. Kimura hit upon Horseback Riding Robot, which can precisely simulate horseback motion ; as a result, he has developed and completed the Horseback Riding Robot, which can be worked by six motors. The Horseback Riding Robot, however, is very expensive. For that reason we have decided to turn over a new leaf and have developed a home machine by realizing one motor type. We proved the muscle strength trainings by use of Horse Riding Robot and a home machine, unlike a existing monotonous and boring muscle training, to be worthwhile and effective. PMID- 20354330 TI - [Musculoskeletal rehabilitation and bone. Locomotion system disorder with aging and rehabilitation]. AB - Muscle weakness and fall of ability for balance occur as becoming old. It is the worst results to fall down, and to break their bones. It is easy to have fracture elder people so that there is osteoporosis, and therefore they cannot walk, and become bedridden For a purpose to prevent that a senior citizen becomes a care state required by fall, we define "the state that fall of ability for balance and locomotive system result from aging and shut ourselves up, and a fall risk rose" as Musculoskeletal Ambulation Disability Syndrome (MADS) . A diagnosis of MADS is performed by criteria. The criteria of MADS is that a person with a history of 11 disorders has the particular degree of ADL independence and motor function. It is important to prevent falling down and do injury of fractures in persons with MADS by performing rehabilitation mainly on dynamic flamingo treatment. PMID- 20354331 TI - [Musculoskeletal rehabilitation and bone. Static balance exercise for preventing falls and fractures]. AB - There is an urgent need to establish measures for dealing with reduced life function in the elderly. Fractures caused by falls are one of the factors that prevent elderly people from living independently, and there is a need for exercises that provide superior balance and more effectively prevent falls. However, although several meta-analyses have been conducted regarding balance, there are few clear guidelines for balance exercises. In the present study, we clarified the development of balance ability by examining the motor development process, and discuss herein the significance of acquisition and maintenance of static balance. We also conducted a literature search regarding effective exercises for static balance impairment, and include a discussion of the effectiveness and limitations of static balance exercises. PMID- 20354332 TI - [Musculoskeletal rehabilitation and bone. Application of motivation theory for rehabilitation of the elderly]. AB - Selection and application of the exercise programs for rehabilitation of the elderly should not only be based on a short-term efficiency, but also be based on the self- determination and motivation of the participants themselves. In this paper, we will review the functional improvement of the elderly by Tai Chi, Hula, Ball Exercise, and Arcade Games, and will discuss about the motivation theory to apply in practice. The intrinsic motivation is the essential element of the theory and is composed of enjoyment, interest and satisfaction. PMID- 20354333 TI - [Nutrition and bone health. Dietary sodium intake and bone health]. AB - Dietary sodium (Na) intake has been known to influence urinary calcium (Ca) excretion. High Na intake has been reported to increase urinary Ca excretion and bone resorption markers, and to be associated with bone loss. In these studies, however, the effect of high Na intake is small, and also affected by other nutrients intakes such as Ca or potassium intakes. Therefore, the association of Na intake and bone health could not be studied alone, but should be studied with full consideration of its interaction with other nutrients. PMID- 20354334 TI - Comparative effects of carvedilol vs bisoprolol for severe congestive heart failure. AB - BACKGROUND: Although carvedilol and bisoprolol are effective medicines for the treatment of patients with heart failure (HF), only a few reports have compared their effects. This study was designed to compare the effects of them in patients with severe HF. METHODS AND RESULTS: A total of 655 consecutive patients with HF, categorized as New York Heart Association Class 3 or 4, were retrospectively investigated. Of these patients, 217 were administered beta-blockers after admission and were divided into 2 groups (carvedilol, n=110; bisoprolol, n=107). No significant differences were observed in their characteristics between the 2 groups prior to the introduction of the beta-blockers. After 18 months of follow up, there were no significant differences in the survival and cardiac event-free rates between the 2 groups. In contrast, there were several significant differences in patients with atrial fibrillation (AF) (carvedilol, n=40; bisoprolol, n=43). The percent changes in heart rate and brain natriuretic peptide level improved significantly in the bisoprolol group than in the carvedilol group. Furthermore, more patients in the bisoprolol group were defibrillated from AF to sinus rhythm than those in the carvedilol group (48% vs 16%; P=0.03). CONCLUSIONS: Our data suggest that the 2 beta-blockers are equally effective in the improvement of severe HF, but bisoprolol shows favorable effects in patients with AF. PMID- 20354335 TI - Importance of morphological changes in T-U waves during bepridil therapy as a predictor of ventricular arrhythmic event. AB - BACKGROUND: Although bepridil is a useful anti-arrhythmic agent for atrial fibrillation, the appearance of serious ventricular arrhythmia, such as torsades de pointes, might be a problem. In this study, T-U wave morphology was evaluated during bepridil therapy and was examined as a predictor of ventricular arrhythmic events. METHODS AND RESULTS: The study population consisted of 113 patients on bepridil therapy. They were divided into 2 groups with and without ventricular arrhythmic events. Morphological changes in T-U waves were analyzed in leads V(2 5). During bepridil treatment, the QTc interval was prolonged from 0.45+/-0.01 to 0.49+/-0.01 s(1/2) in all patients (P<0.0001) and any type of T-U wave change (fused U, slurred, bifid, biphasic or negative) appeared in 73% of event-free and 100% of event groups. In univariate analysis, QTc interval before bepridil (P=0.028), a wide QRS complex (P=0.042) before bepridil, biphasic (P=0.027) or negative (P=0.002) T-U waves in the stable phase, and the new appearance of biphasic (P=0.004) or negative (P<0.0001) T-U waves exhibited significant differences. In multivariate analysis, only newly appeared negative T-U wave exhibited a significant difference (odds ratio 10.13, 95% confidence interval = 0.031-2.302, P=0.041). CONCLUSIONS: In patients with stable bepridil treatment, a change in T-U wave morphology might be a useful predictor of ventricular arrhythmia assisting the QT interval. PMID- 20354337 TI - Effects of removing the adventitia on the mechanical properties of ovine femoral arteries in vivo and in vitro. AB - BACKGROUND: The aims were to characterize in muscular arteries (a) the passive and active effects of the adventitia on vessel biomechanical properties and conduit function (CF), and (b) potential differences between the adventitial role in elastic and muscular arteries. METHODS AND RESULTS: Ovine femoral arteries were studied in vivo and in vitro (reduced smooth muscle-tone) in a circulation mock-up during hemodynamic conditions similar to those found in vivo. Pressure and diameter were assessed before and after removing the adventitia. The arterial compliance, distensibility, stiffness beta-index and CF were quantified. Results were compared with those obtained in brachiocephalic trunks. In vivo, after removing the adventitia there was a nonsignificant diameter reduction and an increase in stiffness (P<0.05). The CF decreased in the early recordings (P<0.02). In vitro, there were no biomechanical changes but vascular dilatation after the adventitia removal. Biomechanical changes associated with the adventitia removal were higher in muscular arteries, whereas diameter changes were major in elastic vessels. CONCLUSIONS: After removing the adventitia, (a) the arterial stiffness and CF were modified in vivo only, suggesting the changes could be ascribed to variations in smooth muscle tone, and (b) changes in elastic and muscular arteries were quantitatively different. PMID- 20354336 TI - Genetic analysis of young adult patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome. AB - BACKGROUND: Although the existence of the young patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome (MFS) has been known, the etiology of their disease has not yet been elucidated. The purpose of the present study was to elucidate the genetic and clinical features of the young patients with aortic disease not having MFS. METHODS AND RESULTS: Eighty young adult patients with aortic disease were examined. They were divided into a definite MFS (n=51) and a non-definite MFS group (n=29) according to the Ghent nosology. Clinical and genetic characteristics were compared between the 2 groups. Among 29 non-definite MFS probands, 1 (3%) FBN1, 2 (7%) TGFBR1, and 3 (10%) TGFBR2 mutations were found, and 4 ACTA2 mutations were found in the 23 probands examined without FBN1, TGFBR1, or TGFBR2 mutations. In total, more than 10 out of 29 (34%) probands in the non-definite MFS group were associated with genetic mutations. Skeletal involvement was less frequent in the non-definite than in the definite MFS group (7% vs 82%, P<0.01). CONCLUSIONS: In the probands with aortic diseases in young who cannot be diagnosed with MFS, mutations other than FBN1 mutations accounted for at least one-third of all causes of aortic disease. PMID- 20354338 TI - Periodic variation and its effect on management and prognosis of Korean patients with acute myocardial infarction. AB - BACKGROUND: The characteristics of the periodic variation in acute myocardial infarction (AMI) and the subsequent effect on management and prognosis have not been fully investigated in a large number of Asian populations. METHODS AND RESULTS: From a prospective, observational multicenter online registry, 4,573 patients diagnosed as AMI in Korea from January to December 2006 were included. The highest incidence of AMI was between 8 a.m. and noon. The number of cases was highest in the winter and lowest in the autumn (13.6 vs 11.4 patients per day, P<0.001). Patients with symptom onset during working hours had a shorter time to first medical contact (203+/-288 min) compared with out-of-hours onset (230+/-288 min, P=0.003). In patients who underwent primary angioplasty, out-of hours symptom onset was associated with a greater time delay in both the patient's and the medical facility's response (door-to-balloon time out-of hours vs working hours: 101+/-54 min vs 84+/-44 min, P<0.001). In patients with ST-segment elevation myocardial infarction, symptoms to first medical contact showed a significant relationship to in-hospital mortality (for every 10 min of symptoms to first medical contact, odds ratio 1.006, 95% confidence interval 1.001-1.012, P=0.018) CONCLUSIONS: Circadian and periodic variation in AMI exists in Korean patients, which resulted in different patient behavior, hospital management and outcomes. PMID- 20354339 TI - Physiologic implications of phosphoinositides and phospholipase C in the regulation of insulin secretion. AB - The secretion of insulin from the pancreatic beta-cell must be commensurate to satisfy the insulin requirements of the organism. This cell has a great flexibility to meet these requirements which are increased not only by the ingestion of nutrients (increase of plasma glucose) but also by the sensitivity of target tissues to insulin as well. The insulin secretion is a complex biochemical event regulated by a host of potential second messenger molecules acting alone or in concert. These events include the cation calcium, which gains access to the beta-cell via the opening of voltage-regulated channels, cAMP and phosphoinositide-derived second messenger molecules, generated as a consequence of phospholipase C (PLC) activation. In this review, we focused on phosphoinositides, PLC/Phosphokinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) cascade in the regulation of insulin secretion. We also described our studies on the mechanism of the beta-cell desensitization using perifused islets. It is suggested that a failure of the signaling events contribute to the pathogenesis of diabetes in which the beta-cell can no longer secrete the required amounts of insulin. It has been observed that chronic exposure to high glucose desensitizes the beta-cells to subsequent stimulation. We suggested that the failure of PLC activation can be attributed in the impairment of insulin secretion by chronic sustained glucose exposure. It may contribute to the vicious circle of impaired insulin secretion leading up to diabetes. PMID- 20354340 TI - A thiamin derivative inhibits oxidation of exogenous glucose at rest, but not during exercise. AB - Thiamin (vitamin B(1)) is known to activate carbohydrate metabolism in part through activation of pyruvate dehydrogenase. The purpose of this study was to investigate the effect of thiamin tetrahydrofurfuryl disulfide (TTFD), a thiamin derivative, on utilization of exogenous glucose by measuring oxidation of (13)C glucose at rest and during prolonged exercise in mice under normal dietary conditions. Mice orally ingested TTFD (0.1 mg/g BW [body weight]) and (13)C glucose (0.8 mg/g BW) or (13)C-lactate (0.1 mg/g BW) plus glucose (0.8 mg/g BW) at rest or before endurance running. The average percent of (13)C atoms in total (12)C+(13)C ((13)C atom%) in expired air after ingestion of (13)C-glucose at rest was significantly lower in the TTFD group than in the control group. No significant difference was found in (13)C atom% in expired air after ingestion of (13)C-glucose and prolonged exercise. In addition, no significant effect of TTFD was found in expired (13)C atom% after ingestion of (13)C-lactate plus glucose at rest. TTFD also had no effect on concentrations of muscle or liver glycogen at rest. These results suggest that TTFD, which is a thiamin derivative, decreases oxidation of exogenous glucose at rest, but not during exercise. PMID- 20354341 TI - Algae consumption and risk of type 2 diabetes: Korean National Health and Nutrition Examination Survey in 2005. AB - The purpose of this study is to examine the relationship between dietary algae (seaweed) consumption and the risk of Type 2 diabetes mellitus in the Korean population. We analyzed data from the Korean National Health and Nutrition Examination Survey in 2005, a nationally representative survey. The study participants included 3,405 males and females aged 20-65 y. Participants were classified into four groups according to the quartiles of total algae consumption frequencies. Proportional odds models were used to assess the relationship between algae consumption and the risk of having diabetes or prediabetes, after adjustment for age, family history of diabetes, education, smoking, alcohol consumption, physical activity, body mass index, waist circumference, triglycerides, total energy intake and food group intakes. The frequency of algae consumption was positively correlated to the consumption of legumes, fruits, fish, and dairy products in both genders (p<0.001). The odds ratios (95% confidence interval) for diabetes vs. prediabetes vs. normoglycemia was 0.66 (0.43-0.99) for males and 0.80 (0.51-1.24) for females in the highest quartile of algae consumption compared to the lowest quartile. Our results suggest that dietary algae consumption may decrease the risk of diabetes mellitus in Korean men. A well-designed prospective study is needed to confirm this association. PMID- 20354342 TI - Effect of fasting on the urinary excretion of water-soluble vitamins in humans and rats. AB - Recent studies showed that the urinary excretion of the water-soluble vitamins can be useful as a nutritional index. To determine how fasting affects urinary excretion of water-soluble vitamins, a human study and an animal experiment were conducted. In the human study, the 24-h urinary excretion of water-soluble vitamins in 12 healthy Japanese adults fasting for a day was measured. One-day fasting drastically decreased urinary thiamin content to 30%, and increased urinary riboflavin content by 3-fold. Other water-soluble vitamin contents did not show significant change by fasting. To further investigate the alterations of water-soluble vitamin status by starvation, rats were starved for 3 d, and water soluble vitamin contents in the liver, blood and urine were measured during starvation. Urinary excretion of thiamin, riboflavin, vitamin B(6) metabolite 4 pyridoxic acid, nicotinamide metabolites and folate decreased during starvation, but that of vitamin B(12), pantothenic acid and biotin did not. As for blood vitamin levels, only blood vitamin B(1), plasma PLP and plasma folate levels decreased with starvation. All water-soluble vitamin contents in the liver decreased during starvation, whereas vitamin concentrations in the liver did not decrease. Starvation decreased only concentrations of vitamin B(12) and folate in the skeletal muscle. These results suggest that water-soluble vitamins were released from the liver, and supplied to the peripheral tissues to maintain vitamin nutrition. Our human study also suggested that the effect of fasting should be taken into consideration for subjects showing low urinary thiamin and high urinary riboflavin. PMID- 20354343 TI - Relation of bone mineral density to vitamin D receptor gene polymorphism and lifestyle factors in Japanese female workers aged 22-44 years: a cross-sectional study. AB - Bone mineral density (BMD) reflects both genetic and lifestyle factors. The aim of this cross-sectional study was to investigate the influence of vitamin D receptor (VDR) gene polymorphism and lifestyle factors on BMD in premenopausal female workers. The subjects were 162 premenopausal female employees aged 22-44 y who worked at a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time and genomic DNA was isolated from peripheral leukocytes. BMD was positively correlated with age, weight, and body mass index (BMI). The genotype frequencies of VDR gene polymorphism detected by TaqI analysis were 77.2, 22.8, and 0.0% for TT, Tt, and tt, respectively. Analysis of covariance with adjustment for age and BMI showed that the mean BMD was significantly lower in subjects with the Tt genotype than in those with the TT genotype. Subjects who drank alcohol also showed a significantly lower BMD if they had the Tt genotype than if they had the TT genotype. According to multiple linear regression analysis, the independent determinants of BMD were age, BMI, and VDR gene polymorphism. Our data show that BMD is negatively correlated with the Tt genotype of the VDR gene, but positively correlated with age and BMI. These findings suggest that analysis of VDR gene polymorphism may be useful for identifying individuals who are susceptible to osteoporosis so that early preventive measures can be provided. PMID- 20354344 TI - Spirulina prevents atherosclerosis by reducing hypercholesterolemia in rabbits fed a high-cholesterol diet. AB - The anti-atherogenic effects of spirulina (Spirulina platensis) were investigated in the New Zealand White (NZW) rabbit model. The animal had hypercholesterolemia induced by being fed a high cholesterol diet (HCD) containing 0.5% cholesterol for 4 wk, and then fed a HCD supplemented with 1 or 5% spirulina (SP1 or SP5) for an additional 8 wk. Spirulina supplementation lowered intimal surface of the aorta by 32.2 to 48.3%, compared to HCD. Serum triglyceride (TG) and total cholesterol (TC) significantly were reduced in SP groups. After 8 wk, serum low density lipoprotein cholesterol (LDL-C) remarkably decreased by 26.4% in SP1 and 41.2% in SP5, compared to HCD. On the other hand, high density lipoprotein cholesterol (HDL-C) was markedly increased in SP1 and SP5 compared with that in the HCD group from 2 to 8 wk. These results suggest that spirulina intake can cause the reduction of hypercholesterolemic atherosclerosis, associated with a decrease in levels of serum TC, TG and LDL-C, and an elevation of HDL-C level. Spirulina may, therefore, be beneficial in preventing atherosclerosis and reducing risk factors for cardiovascular diseases. PMID- 20354345 TI - Emulsification of coenzyme Q10 using gum arabic increases bioavailability in rats and human and improves food-processing suitability. AB - We evaluated the characteristics of a coenzyme Q(10) (CoQ(10)) formulation created with gum arabic. We defined the formulation's "modulus of inclusion," a reference index of the emulsified state, as the CoQ(10) not extracted by hexane as a percentage of the total CoQ(10) content of the formulation. The emulsified CoQ(10) formulation had a smaller particle size and larger modulus of inclusion value than the equivalent unemulsified formulation. In a kinetic study in rats, serum CoQ(10) levels were significantly greater with the emulsified CoQ(10) formulation than with the equivalent unemulsified formulation, which barely increased the levels. In a human study, oral intake of the emulsified formulation significantly increased plasma CoQ(10) levels, which peaked 6 h after intake, compared with the equivalent unemulsified formulation or CoQ(10) bulk powder. There was a significant positive correlation between baseline plasma CoQ(10) and total cholesterol levels, but no correlation was observed between absorption of CoQ(10) and baseline CoQ(10) levels. The emulsified CoQ(10) formulation was highly stable against heat and high humidity and in the presence of some materials (magnesium oxide, vitamin C, and vitamin E). In conclusion, emulsification of CoQ(10) using gum arabic increased bioavailability in both rats and humans and improved suitability for food processing. PMID- 20354346 TI - Hypolipidemic effect of Pleurotus eryngii extract in fat-loaded mice. AB - Pleurotus eryngii water extract (PEE), which showed the most significant inhibitory activity against pancreatic lipase in vitro among eight edible mushrooms, was investigated to determine the mechanism of its anti-lipase activity in vitro and its hypolipidemic effect in fat-loaded mice. The inhibitory effects of mushroom extracts on pancreatic lipase activity were examined using 4 methylumbelliferyl oleate (4-MUO) or trioleoylglycerol emulsified with lecithin, gum arabic or Triton X-100 as a substrate. For in vivo experiments, blood samples were taken after oral administration of corn oil and [(3)H]trioleoylglycerol with or without PEE to food-deprived mice. PEE inhibited hydrolysis of 4-MUO and trioleoylglycerol emulsified with lecithin or Triton X-100, but not that of trioleoylglycerol emulsified with gum arabic. PEE suppressed the elevations of plasma and chylomicron triacylglycerol levels after oral administration of corn oil, but had no effect on lipoprotein lipase activity. [(3)H]Trioleoylglycerol absorption was also decreased by administration of PEE. The results of in vitro studies suggest that PEE may prevent interactions between lipid emulsions and pancreatic lipase. The hypolipidemic effect of PEE in fat-loaded mice may be due to low absorption of fat caused by the inhibition of pancreatic lipase. PMID- 20354347 TI - Oral administration of acidic xylooligosaccharides prevents the development of atopic dermatitis-like skin lesions in NC/Nga mice. AB - We examined whether two types of xylooligosaccharides (neutral or acidic xylooligosaccharides) derived from hardwood kraft pulp ameliorate the development of atopic dermatitis (AD)-like skin lesions induced by repeated application of picryl chloride (PiCl) in NC/Nga mice. Oral administration of acidic xylooligosaccharides at a daily dose of 100 mg/kg significantly prevented the development of AD-like skin lesions. Serum histamine level was significantly suppressed, but serum total IgE level was not significantly suppressed. Moreover, the secretion of inflammatory cytokine IL-12 from splenic lymphocytes was significantly suppressed. On the other hand, neutral xylooligosaccharides showed no significant preventive effect on the development of AD-like symptoms. These results suggest that oral administration of acidic xylooligosaccharides may be effective in preventing the development of AD-like skin disease and one of the mechanisms is the suppressive effect on IL-12. PMID- 20354348 TI - Hepatoprotective effects of flavonoids from shekwasha (Citrus depressa) against D galactosamine-induced liver injury in rats. AB - We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3',4',5,6,7,8-hexamethoxyflavanone (citromitin), 4',5,6,7,8 pentamethoxyflavone (tangeretin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-alpha and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF alpha and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice. PMID- 20354349 TI - Consumption of curcumin elevates fecal immunoglobulin A, an index of intestinal immune function, in rats fed a high-fat diet. AB - This study was conducted to elucidate the effects of dietary polyphenols on intestinal immunoglobulin A (IgA) response and mucin levels in rats fed a high fat diet. In experiment 1, rats were fed a high-fat diet with or without several polyphenols including curcumin, rutin, D(+)-catechin, ellagic acid and quercetin at the level of 0.5%. Among the polyphenols examined, consumption of curcumin markedly elevated the level of IgA in feces and colon contents. In experiment 2, rats were fed a high-fat diet or a low-fat diet with or without 0.5% curcumin. Fecal level of IgA was higher in the high-fat diet group than in the low-fat diet group. In the rats fed the high-fat diet, dietary curcumin elevated fecal IgA, but not in those fed the low-fat diet. These results imply a novel effect of curcumin on intestinal IgA in animals fed a high-fat diet. PMID- 20354350 TI - The soy isoflavone equol enhances antigen-specific IgE production in ovalbumin immunized BALB/c mice. AB - Although an immunomodulatory role of the soy isoflavone genistein has been demonstrated, the effects of other soy isoflavones on induction of antigen (Ag) specific immune responses are not known. In this study, we therefore investigated the effects of daidzein and equol on ovalbumin (OVA)-specific T cell and B cell responses in BALB/c mice. Mice that had been treated with 20 mg/kg equol showed a significantly higher level of OVA-specific IgE than control mice. Levels of interferon (IFN)-gamma and interleukin (IL)-4 production were not different between the control and equol groups. However, IL-13 production level in mice administered 20 mg/kg equol was significantly higher than that in control mice. Strong induction of OVA-specific IgE production by equol was also observed in ovariectomized BALB/c mice, suggesting that the immunomodulatory effect of equol is not affected by endogenous estrogen. PMID- 20354351 TI - Coenzyme Q10 decreases TNF-alpha and IL-2 secretion by human peripheral blood mononuclear cells. AB - The beneficial effect of coenzyme Q10 (CoQ10) on human health occurs through various mechanisms including the possibility of immunomodulation. Therefore, the purpose of study was to examine the in vitro effect of CoQ10 on cytokine production and superoxide anion generation by human peripheral blood mononuclear cells (PBMC). 2x10(6)/mL PBMC obtained from 19 volunteers were incubated for 24 h without or with 0.6, 1.25, 2.5 and 5.0 muM of CoQ10. The production of the following cytokines were examined: IL-1beta, IL-1ra, IL-6, IL-10, IL-2 and IFNgamma. Superoxide anion production was examined by incubation of 4x10(6)/mL cells with CoQ10 and 2x10(-3) mM phorbol merystate acetate (PMA) for 60 min. The production of the proinflammatory cytokines IL-1beta, IL-6 and IFNgamma and that of the anti-inflammatory cytokines IL-1ra and IL-10 by PBMC was not affected by CoQ10, whereas TNFalpha secretion was significantly decreased when the cells were incubated with 0.6 and 1.25 muM of CoQ10. On the other hand, increasing doses of CoQ10 caused mild, but statistically significant inhibition of IL-2 secretion. The generation of superoxide anion by PBMC did not differ significantly between cells incubated with or without CoQ10 at concentrations between 0.3 and 5.0 muM. The results suggest that CoQ10 exerts a certain effect on cytokine production by PBMC related to its capacity to modulate human immune function. PMID- 20354352 TI - Effects of growth hormone on body proportions in Turner syndrome compared with non-treated patients and normal women. AB - BACKGROUND: The majority of anthropometric assessments in Turner syndrome (TS) patients has focused on height. AIM: To analyze body proportions in young adult TS patients either treated or not treated with rhGH, and to compare them with a group of age-matched healthy women. SUBJECTS AND METHODS: Standing height, sitting height, weight, foot and leg lengths, arm span, head circumference, biliac and biacromial diameters were measured in 52 non-treated TS patients, 30 treated with rhGH and 133 healthy women. RESULTS: Age at the start of rhGH therapy varied from 7.8 to 15.1 yr (10.0+/-1.3 yr), the duration of treatment from 2.8 to 8.2 yr (3.7+/-1.5 yr) and the mean recombinant human GH (rhGH) dose was 0.42 mg/kg/week (from 0.32 to 0.50 mg/kg/week). Nontreated patients did not show any difference in anthropometric variables when compared with the treated ones, except for hand length (p=0.02) and height (p=0.05), which were increased in the treated group. All anthropometric variables, except head circumference, were different when comparing TS patients (either treated or not) with age matched healthy women. CONCLUSION: Brazilian TS patients either treated or not with rhGH showed almost no differences in terms of their body proportions. This result is probably due to the late age at the start of treatment, and/or the short period of rhGH administration. Hand length was different between the groups, showing the importance of including the extremities in body proportion assessment during rhGH treatment of TS patients. PMID- 20354353 TI - Progesterone is primary regulator of Cdk2ap1 gene expression and tissue-specific expression in the uterus. AB - Proliferation of endometrial cells is a prerequisite step for functional differentiation in the uterus. A tumor suppressor gene, Cyclin-dependent kinase 2 associated protein 1 (Cdk2ap1) mRNA was detected in the pregnant uterus and was suggested to be involved in cell proliferation. However, its roles and the mechanisms regulating its expression are largely unknown. In this study, the role of steroid hormones in the expression of Cdk2ap1 was examined using RT-PCR, Northern blotting and in situ hybridization methods. Cdk2ap1 mRNA was highly expressed during the proestrus phase and was mainly localized in the epithelium and subepithelium. Its expression was induced by a single injection of estradiol and progesterone, but the effect of progesterone was stronger than that of estradiol. Injections of progesterone (P1,2) on 2 consecutive days induced Cdk2ap1 expression in the endometrium with the same patterns observed in the proestrus phase, but injections of estradiol (E1,2) on 2 consecutive days did not induce expression. The Cdk2ap1 mRNA level was decreased by combined treatment of progesterone and estradiol (E1+P2,3). RU486 suppressed completely the Cdk2ap1 mRNA expression in P1,2 while ICI 182,780 did not in E1+P2,3. In the uteri on day 4 of gestation, expression of Cdk2ap1 also was regulated by progesterone as expected. Cdk2ap1 mRNA expression was totally suppressed by RU486 but not by ICI 182,780. Thus, it is suggested that Cdk2ap1 expression is primarily regulated by progesterone and the progesterone receptor in uterus and is mainly localized to proliferating tissues. PMID- 20354354 TI - Microalbuminuria is associated with impaired arterial and venous endothelium dependent vasodilation in patients with Type 2 diabetes. AB - BACKGROUND: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. AIM: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. MATERIAL AND METHODS: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. RESULTS: Patients were normotensive (systolic arterial pressure: 131.1+/-10.6 mmHg) and on good metabolic control (HbA(1c): 6.6+/-0.6%). Microalbuminuric patients presented impaired venous (32.9+/-17.4 vs 59.3+/-26.5%; p=0.004) and arterial vasodilation (1.8+/-0.9 vs 5.1+/-2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). CONCLUSIONS: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis. PMID- 20354355 TI - The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: Mutational hot-spot or founder effect? AB - BACKGROUND: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (AIPR304X) represents, together with the "Finnish mutation" Q14X, the most common one. METHODS: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed. RESULTS: Analysis of chromosome 11' genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1+/-6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype. CONCLUSION: These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds. PMID- 20354356 TI - PPARalpha agonist prevented the apoptosis induced by glucose and fatty acid in neonatal cardiomyocytes. AB - OBJECTIVE: We investigated the effect of peroxisome proliferator activator receptors alpha (PPARalpha) on cardiomyocyte apoptosis induced by glucose and fatty acid, and if high glucose levels could increase fatty acid-induced apoptosis. METHODS: Cardiomyocytes were maintained in Dulbecco's Modified Eagle Medium and divided into 5 groups: Group N (control Group); Group G (exposed to 25.5 mmol/l glucose); Group L (exposed to 5 mmol/l glucose, fatty acid); Group H (exposed to 25.5 mmol/l glucose and fatty acid); Group I (exposed to 25.5 mmol/l glucose, fatty acid and Wy14643). Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Immunocytochemistry staining detected PPARalpha's expressing, and western blotting detected PPARalpha and nuclear factor kappaB's (NF-kappaB) protein level. RESULTS: Exposure to fatty acid resulted in a significant increase of cardiomyocytes apoptosis, with the extension of NF-kappaB formation, whereas exposure to 25.5 mmol/l glucose had no influence on the apoptosis rate. However, combination with fatty acid and high glucose concentration had induced more apoptosis with the up-regulation of NF kappaB formation. The fatty acid and glucose-induced effects were improved by Wy14643, with down-regulation of NF-kappaB formation. CONCLUSION: These results suggested that in neonatal cardiomyocytes, fatty acid and glucose in combination with fatty acid induced apoptosis via NF-kappaB formation and activation of apoptosis pathways; glucose in combination with fatty acid induce more apoptosis rate for the more NF- kappaB formation, activation of the PPARalpha can reverse such apoptosis effect. The results also suggest that gluco-lipotoxicity may play a central role in the development of diabetic cardiomyopathy, and PPARalpha agonist may be an effective drug in treating the diabetic cardiomyopathy. PMID- 20354357 TI - Case studies in academic medicine. PMID- 20354359 TI - Longitudinal integrated clerkships. PMID- 20354360 TI - The surest way to prevent burnout in medical school and beyond. PMID- 20354363 TI - How valid are standard self-assessment scales for international medical graduates? PMID- 20354364 TI - Rethinking invasive procedural training. PMID- 20354366 TI - Commentary: do medical schools have a responsibility to train physicians to meet the needs of the public? The case of persistent rural physician shortages. AB - Persistent shortages of rural physicians have plagued the U.S. health care system for much of the last century. Recent, sharp declines in the number and proportion of U.S. medical students entering primary care have exacerbated this chronic problem because primary care physicians are the foundation of rural health care systems. The article by Chen and colleagues in the current issue of this journal replicates findings of a study 15 years ago by the author of this commentary and his colleagues that demonstrated that a relatively small number of medical schools are responsible for a large share of all of the rural physicians in the country. The lack of progress in the ensuing 15 years is distressing because there is now excellent evidence that targeted rural tracks in medical schools including selective admissions of students from rural backgrounds and supportive integrated curricula-yield dramatic increases in the number of students choosing rural careers. U.S. medical schools-supported in large part by public funds-have a responsibility to ensure that the specialty choices and practice locations of their graduates meet the needs of the nation at large, as well as the rural and underserved communities in the regions they serve. PMID- 20354367 TI - Commentary: deconstructing gender difference. AB - In Japan, as in the United States, a growing proportion of physicians are women. Hence, the different social roles that men and women occupy and the gendered norms for behavior are increasingly relevant in ensuring that male and female physicians have equal opportunity to participate and advance in all aspects of medicine. Elsewhere in this issue, Nomura and colleagues report on a large survey of primary care residents in Japan. They found that on average women's self-rated confidence on many clinical tasks was lower than men's. This is not surprising given similar gender differences in self-assessed competence in other research and the socialization of women in virtually all cultures to be modest. The actual differences in average scores were small suggesting considerable overlap in the distributions of responses from male and female residents. In addition, research from other countries finds no association between physicians' self-reported confidence in clinical tasks and objective measures of competence on which female physicians rate at or above the level of their male counterparts. Congruent with different social roles for men and women, Nomura and colleagues also found gender differences in the average responses about work-family priorities and aspirations toward leadership, but some women indicated a desire for research careers and some men were "life-oriented." The author of this commentary argues that to draw conclusions about all male or all female physicians from average differences of a large group of residents may reinforce gender stereotypes that continue to impede each individual female physician's career advancement and each individual male physician's struggle for work-life balance. PMID- 20354368 TI - Commentary: using medical student case presentations to help faculty learn to be better advisers. AB - The case presentation is a time-honored tradition in clinical medicine, and medical journals and national conferences have provided a forum for this type of scholarship for more than a century. Case presentations can also be used by educators as a means to understand challenging learner experiences, and by doing so, lead to advances in the practice of medical education. Medical school faculty are asked to serve in student advisor roles, yet best practices for student advising are not known. Unlike clinicians, who often discuss difficult patient cases, medical educators do not typically have opportunities to discuss challenging student cases to learn how best to support trainees. In this commentary, the authors-from the Johns Hopkins University School of Medicine Colleges Advisory Program (CAP), a longitudinal advising program with the goal of promoting personal and professional development of students-describe the novel quarterly Advisory Case Conference, where medical student cases can be confidentially presented and discussed by faculty advisors, along with relevant literature reviews, to enhance faculty advising skills for students. As medical student advising needs often vary, CAP advisors employ adult learning principles and emphasize shared responsibility between advisor and advisee as keys to successful advising. Unlike traditional clinical case conferences, the Advising Case Conference format encourages advisors to share perspectives about the cases by working in small groups to exchange ideas and role-play solutions. This model may be applicable to other schools or training programs wishing to enhance faculty advising skills. PMID- 20354369 TI - Commentary: profiling by appearance and assumption: beyond race and ethnicity. AB - In this issue, Acquaviva and Mintz highlight issues regarding racial profiling in medicine and how it is perpetuated through medical education: Physicians are taught to make subjective determinations of race and/or ethnicity in case presentations, and such assumptions may affect patient care. The author of this commentary believes that the discussion should be broadened to include profiling on the basis of general appearance. The author reports personal experiences as someone who has profiled and been profiled by appearance-sometimes by skin color, sometimes by other physical attributes. In the two cases detailed here, patient care could have been affected had the author not become aware of his practices in such situations. The author advocates raising awareness of profiling in the broader sense through training. PMID- 20354370 TI - Commentary: linking cultural competence training to improved health outcomes: perspectives from the field. AB - The Institute of Medicine report entitled Unequal Treatment recommended that all health care professionals receive training in cross-cultural communication-also called "cultural competence"-as one potential strategy for addressing racial or ethnic disparities in health care. Although evidence shows that cultural competence training improves the attitudes, knowledge, and skills of physicians as well as patients' ratings of care, no definitive evidence has yet linked this training to improved health outcomes. Recently, there has been great interest in the field of cultural competence, including an expressed desire for a better understanding of its key principles, of effective ways of engaging clinicians in this area of instruction, and of the link between training and health outcomes. On the basis of years of experience in the field, the authors share key perspectives in all of these areas, with particular focus on a set of guidelines for measuring the impact of cultural competence training on health care outcomes. The authors maintain that cultural competence represents an important building block of clinical care, as well as a skill set that is central to professionalism and quality. Cultural competence training should be evaluated in a stepwise fashion by using the tools of health services research and the principles of quality improvement, and it should be held to the same standards as other educational interventions and activities. Just as medicine strives to meet other challenges in U.S. health care, so should it focus on developing the skills needed to care for the country's diverse population. PMID- 20354371 TI - Commentary: a call for culture change in academic medicine. AB - Disappointed by the lack of progress in the advancement of women and underrepresented minority faculty to senior positions and leadership roles in academic medicine and concerned by the prospect that these valuable faculty resources were being lost, a group of five medical school deans agreed to embark on a multiyear project to change the culture of their medical schools for these underrepresented faculty. This commentary outlines the rationale and motivation for the project and sets the stage for future reports from and wider participation in this initiative. PMID- 20354372 TI - Reports of the decline of empathy during medical education are greatly exaggerated: a reexamination of the research. AB - PURPOSE: Research is said to show that empathy declines during medical school and residency training. These studies and their results were examined to determine the extent of the decline and the plausibility of any alternative explanations. METHOD: Eleven studies published from 2000 to 2008 which reported empathy at various stages of physician training were reexamined. Their results were transformed back to the original units of the rating scales to make results more interpretable by reporting them in the metric of the original anchors. Next, the relationship between empathy ratings and response rates were examined to see whether response bias was a plausible threat to the validity of the empathy decline conclusion. RESULTS: The changes in mean empathy ranged across the 11 studies from a 0.1-point increase in empathy to a 0.5-point decrease, with an average of a 0.2-point decline for the 11 studies (ratings were on 5-point, 7 point, and 9-point scales). Mean ratings were similar in medical school and residency. Response rates were low and-where reported-declined on average about 26 percentage points. CONCLUSIONS: Reexamination revealed that the evidence does not warrant the strong, disturbing conclusion that empathy declines during medical education. Results show a very weak decline in mean ratings, and even the weak decline is questionable because of the low and varying response rates. Moreover, the empathy instruments are self-reports, and it isn't clear what they measure-or whether what they measure is indicative of patients' perceptions and the effectiveness of patient care. PMID- 20354373 TI - Which medical schools produce rural physicians? A 15-year update. AB - PURPOSE: Despite continued federal and state efforts to increase the number of physicians in rural areas, disparities between the supply of rural and urban physicians persist. The authors examined the training of the rural physician workforce in the United States. METHOD: Using a national cross-sectional analysis of the 2005 American Medical Association and American Osteopathic Association Masterfile physician data, the authors examined a 10-year cohort of clinically active MD and DO physicians who graduated from medical school between 1988 and 1997. RESULTS: Eleven percent (20,037) of the physician cohort were currently practicing in a rural location in 2005. Eighteen percent (2,045) of osteopathic medical school graduates were currently practicing in a rural location. Twenty three percent (6,282) of family physician graduates practiced in rural areas. Women continue to be less likely than men to practice in rural areas, although the gap is narrowing. Rural residency trainees were over three times more likely to practice in rural areas (RR = 3.4, P < .001). CONCLUSIONS: The proportion and number of physicians entering rural practice has remained stable compared with earlier analyses. However, recent trends such as declining primary care interest are not yet reflected in these data and may portend worsening shortages of rural physicians. PMID- 20354374 TI - Efforts to graduate more primary care physicians and physicians who will practice in rural areas: examining outcomes from the university of Minnesota-duluth and the rural physician associate program. AB - PURPOSE: To compare practice choices (primary care or specialty) and practice locations (rural or metropolitan) of medical students at the Duluth and Twin Cities (Minneapolis and St. Paul; TC) campuses of the University of Minnesota (UMN). In the early 1970s, Minnesota created two medical education programs at UMN to increase the number of rural and primary care physicians: the first two years of medical school at UMN-Duluth, where the program focuses on recruiting students who will be rural family physicians, and the Rural Physician Associate Program (RPAP) elective, a nine-month, longitudinal immersion experience with a preceptor in a rural community. METHOD: In 2008, the authors analyzed outcomes for four student groups: (1) UMN-Duluth and (2) UMN-TC medical students who participated in RPAP and (3) UMN-Duluth and (4) UMN-TC students who did not participate in RPAP. UMN medical students complete their first two years on either campus; they can apply to RPAP for their third year. Non-RPAP students spend most of their third- and fourth-year rotations in the Twin Cities metropolitan area. RESULTS: The UMN-Duluth and RPAP students were most likely to select a rural location and primary care practice. UMN-TC, non-RPAP students followed national trends, choosing predominantly metropolitan and specialty practices. CONCLUSIONS: RPAP and UMN-Duluth provide significant, complementary educational programs that lead more graduates to choose rural and primary care practices. Efforts across the nation to address the crisis in rural primary care should build on these successful efforts. PMID- 20354375 TI - Attributes affecting the medical school primary care experience. AB - PURPOSE: Favorable primary care (PC) experiences might encourage more medical students to pursue generalist careers, yet academicians know little about which attributes influence the medical school PC experience. The authors sought to identify such attributes and weight their importance. METHOD: Semistructured interviews with 16 academic generalist leaders of family medicine, general internal medicine, and general pediatrics led to the development of a Web-based survey, administered to a national sample of 126 generalist faculty. Survey respondents rated (on a nine-point Likert-like scale) the importance of each interview-generated PC medical school attribute and indicated (yes/no) whether outside experts' assessment of the attributes would be valid. The authors assessed interrater agreement. RESULTS: Interview thematic analysis generated 58 institutional attributes in four categories: informal curriculum (23), institutional infrastructure (6), educational/curricular infrastructure (6), and specific educational experiences (23). Of these 58, 31 (53%) had median importance ratings of >7 (highly important). For 14 of these (45%), more than two thirds of respondents indicated external expert surveys would provide a valid assessment. Of the 23 informal curriculum attributes, 20 (87%) received highly important ratings; however, more than two-thirds of respondents believed that external expert survey ratings would be valid for only 4 (20%) of them. Strong agreement occurred among respondents across the generalist fields. CONCLUSIONS: Academic generalist educators identified several attributes as highly important in shaping the quality of the medical school PC experience. Informal curriculum attributes appeared particularly influential, but these attributes may not be validly assessed via expert surveys, suggesting the need for other measures. PMID- 20354376 TI - Retention of J-1 visa waiver program physicians in Washington State's health professional shortage areas. AB - PURPOSE: To determine whether the Conrad Program, which allows states to recruit 30 foreign-trained physicians per year to work in underserved settings, is meeting its goal of increasing the number of physicians in Washington State's underserved areas. Participating physicians have completed their residency training in, and want to continue residing in, the United States. METHOD: The authors identified all J-1 visa waiver physicians assigned to employers in Washington between 1995 and 2003, tracked them (whenever possible) through public databases to their current locations, and surveyed them about their experiences in, and subsequent to, the program. RESULTS: The authors tracked 141 of 155 physicians (91%). Of those 141, 77 (55%) responded to the survey. These respondents reported that they remained with their J-1 waiver employers a median of 23 (range: 0-120) months longer than their required commitment periods and that they remained in practices serving primarily underserved populations for, on average, 34 (0-120) consecutive months after fulfilling their commitments. After leaving J-1 waiver employers, 35 of 47 physicians (74%) who served in rural areas moved toward more urban areas, and 57% (80/141) still live in the state. Whereas most expressed satisfaction with the program, 29/77 (38%) felt employers should have shown them more respect. CONCLUSIONS: In Washington State, the Conrad Program has increased the number of physicians in underserved areas who frequently stay beyond their obligations. The significant movement away from rural areas for postobligation employment, however, highlights the long-term need to continue state efforts to recruit physicians to these areas. PMID- 20354377 TI - Perspective: private schools of the Caribbean: outsourcing medical education. AB - Twenty-five percent of the U.S. physician workforce is made up of international medical graduates (IMGs), a growing proportion of whom (27% in 2005) are U.S. citizens. Most IMGs graduate from "offshore medical schools" (OMSs), for-profit institutions primarily located in the Caribbean region and established to train U.S. students who will return home to practice medicine. Following the recent call for a larger physician workforce, OMSs rapidly increased in number. Unlike U.S. schools, which must be accredited by the Liaison Committee on Medical Education, OMSs are recognized by their home countries and may not be subject to a rigorous accreditation process. Although gaps in specific data exist, a closer look at OMSs reveals that most enroll three groups of students per year, and many educate students initially at "offshore campuses" and later at clinical sites in the United States. Students from some OMSs are eligible for the U.S. Federal Family Education Loan Program. The lack of uniform data on OMSs is problematic for state medical boards, which struggle to assess the quality of the medical education offered at any one school and which, in some cases, disapprove a school. With the United States' continued reliance on IMGs to meet its health needs, the public and the profession will be best served by knowing more about medical education outside of the United States. Review of medical education in OMSs whose graduates will become part of U.S. health care delivery is timely as the United States reforms its health-care-delivery system. PMID- 20354378 TI - The teachable moment. PMID- 20354379 TI - Activities, productivity, and compensation of men and women in the life sciences. AB - PURPOSE: To determine whether professional activities, professional productivity, and salaries of life sciences faculty differ by gender. The authors undertook this study because previous studies found differences in the academic experiences of women and men. METHOD: In 2007, the authors conducted a mailed survey of 3,080 life sciences faculty at the 50 universities whose medical schools received the greatest amount of National Institutes of Health funding in 2004. The response rate was 74% (n = 2,168). The main outcome measures were a faculty member's total number of publications; number of publications in the past three years; average impact score of the journals in which he or she had published; professional activities; work hours per week; the numbers of hours spent specifically in teaching, patient care, research, professional activities, and administrative activities; and annual income. RESULTS: Among professors, the women reported greater numbers of hours worked per week and greater numbers of administrative and professional activities than did the men. Female faculty members reported fewer publications across all ranks. After control for professional characteristics and productivity, female researchers in the life sciences earned, on average, approximately $13,226 less annually than did their male counterparts. CONCLUSIONS: Men and women in the academic life sciences take on different roles as they advance through their careers. A substantial salary gap still exists between men and women that cannot be explained by productivity or other professional factors. Compensation and advancement policies should recognize the full scope of the roles that female researchers play. PMID- 20354380 TI - Do women residents delay childbearing due to perceived career threats? AB - PURPOSE: To assess gender differences among residents regarding their plans to have children during residency and determine the most influential reasons for these differences. METHOD: Using the Health Belief Model as a framework, the authors created an instrument to survey 424 residents from 11 residency programs at three academic medical institutions about their intentions to have children during residency. The authors developed a scale to assess the perceived career threats of having children during residency, evaluated its psychometric properties, and calculated the effect of the mediators. RESULTS: The response rate was 77% (328/424). Forty-one percent of men versus 27% of women planned to have children during residency (P = .01). The instrument measured four career threats-extended training, loss of fellowship positions, pregnancy complications, and interference with career plans-on a five-point Likert scale. The scale had a Cronbach alpha of 0.84 and an eigenvalue of 2.2. Compared with men, women had higher scores for each item and a higher mean score (2.9 versus 2.1, P = .001), signifying greater belief in the potential of pregnancy to threaten careers. After adjusting for age, institution, postgraduate year, and knowledge of parental leave policies, women were less likely to plan to have children during residency (odds ratio 0.46 [95% confidence interval 0.25-0.84]). In mediation analysis, threats to career explained 67% of the gender variance. CONCLUSIONS: Women residents intentionally postpone pregnancy because of perceived threats to their careers. Medical educators should be aware of these findings when counseling female trainees. PMID- 20354381 TI - Gender differences in clinical confidence: a nationwide survey of resident physicians in Japan. AB - PURPOSE: The number of women physicians is increasing in Japan. The authors investigated gender differences in self-perceptions of clinical confidence. METHOD: This cross-sectional study was conducted in March 2007 by using a stratified random sample of 1,124 second-year resident physicians. Residents' confidence levels were assessed, using four-point Likert scales (e.g., 1 for "not at all" to 4 for "very much"), in four competency sets: physical exams, procedural skills, interpretations of clinical tests, and physician-patient relationships and social service application. Gender effect was investigated for clinical confidence levels by general linear models adjusting for age, types of hospitals, number of clinical experiences, satisfaction with residency conditions, future career, and perspectives on life and work. RESULTS: The overall mean confidence scores in the four sets ranged between 2.9 and 3.1. Compared with men, women were younger (P = .001), more likely to be oriented more to life than to work (P < .001), less interested in doctor of medical science degrees (P = .001), and less likely to be satisfied with residency conditions (P = .020). A significantly greater proportion of women chose "family" (70% versus 54% for men) as "the most important thing in life." Compared with men, women were less confident in the majority of competency areas even after adjusting for the number of clinical experiences. CONCLUSIONS: This nationwide resident survey demonstrated gender differences in clinical confidence levels. Future studies require careful monitoring of self-confidence and its impact on physicians' professional development. PMID- 20354382 TI - Case study: a midclerkship crisis-lessons learned from advising a medical student with career indecision. AB - Advising medical students is a challenging task. Faculty who serve as advisors for students require specific skills and knowledge to do their jobs effectively. Career choice is one of the many complex issues about which medical students often seek assistance from a faculty advisor. The authors present a case of a third-year medical student with career indecision, with a focus on the various factors that may be influencing her thinking about career choice. Key advising principles are provided as a framework for the discussion of the case and include reflection, self-disclosure, active listening, support and advocacy, confidentiality, and problem solving. These principles were developed as part of the Advising Case Conference series of the Johns Hopkins University School of Medicine Colleges Advisory Program. Emergent themes from the case included a student's evolving professional identity, a student's distress and burnout, lifestyle considerations, and advisor bias and self-awareness. The authors propose reflective questions to enhance meaningful discussions between the advisor and student and assist in problem solving. Many of these questions, together with the key advising principles, are generalizable to a variety of advising scenarios between advisors and learners at all levels of training. PMID- 20354383 TI - Long-term effectiveness of patient-centered training in cultural competence: what is retained? What is lost? AB - PURPOSE: To determine whether the effects of a patient-centered cultural competence curriculum could be sustained for one year. METHOD: In 2006, 57 fifth year medical students at National Taiwan University were randomly assigned either to a group that received training in patient-centered cross-cultural communication skills or one that received no training. Students' scores on objective structured clinical exams (OSCEs) were compared in the realms of exploring (1) patient perspectives and (2) social factors related to illness, immediately after training (OSCE1) and one year after training (OSCE2). RESULTS: Regarding students' exploration of patient perspectives, the intervention group scored significantly higher than the control group at OSCE1, but there was a significant decrease from OSCE1 to OSCE2 in the intervention group and no significant difference between the intervention and control group at OSCE2. Regarding students' exploration of social factors related to illness, the intervention group scored significantly higher than the control group at OSCE1, with a nonsignificant decrease from OSCE1 to OSCE2 in the two groups, such that the intervention group again scored higher than the control group in OSCE2. CONCLUSIONS: The effect of a patient-centered cultural competence training curriculum on students' exploration of social factors related to illness was sustained to a significant degree after one year, whereas the effects on students' exploration of patient perspectives were not. Further research is needed to determine the extent to which additional training can prevent the loss of student skills. PMID- 20354384 TI - Artist statement: "the disaster series". PMID- 20354385 TI - Medicine and the arts. Pride and prejudice: [excerpt] by Susan B. Arjmand. Commentary. PMID- 20354387 TI - A baccalaureate-MD program for students from medically underserved communities: 15-year outcomes. AB - Liaison Committee on Medical Education standard MS-8 requires medical schools to partner with other educational institutions or develop programs to make medical education more accessible to potential applicants from diverse backgrounds. From 1994 to the present, Baylor College of Medicine and the University of Texas-Pan American (UTPA) have partnered to offer a BS-MD program to increase access to medical education for students from South Texas, a predominantly Latino, largely medically underserved region. Since its inception in 1994, the Premedical Honors College (PHC) has produced 134 medical school matriculants (as of 2008), an average of 12 students per year since 1998, when the first program graduates matriculated to medical school. This represents a significant increase; only 10 students entered medical school from the region's five undergraduate institutions at baseline year 1994, including six from UTPA. Of those matriculating to medical school, through the PHC 110 (82%) are from underrepresented minority backgrounds, and 106 (79%) are Latino. In addition, the program has produced 65 MDs to date; 55 (85%) are Latino. Twenty PHC participants have already completed residency training and are practicing, 12 of those in or near South Texas. As of 2008, 44 were completing residencies or fellowships, 9 in South Texas, and several have expressed a desire to return to South Texas eventually to practice. Six PHC graduates are academic faculty members (four clinical instructors and two assistant professors), all of them Latino. These results suggest that pipeline strategies involving academic partnerships can have a meaningful impact on diversity in medical education. PMID- 20354388 TI - Staying connected: Native American women faculty members on experiencing success. AB - PURPOSE: To document how medical school faculty who are Native American women describe their sense of personal and professional success, so that mentoring can be better informed and diversity increased. METHOD: This qualitative study was designed using snowball sampling methodology. Open-ended questions were developed with the authors' expertise and asked of five Native American women physician faculty participants until saturation was achieved. Transcripts were coded, organized, and interpreted to generate tentative themes and working hypotheses. The study was completed in 2006 and 2007. RESULTS: Native American women defined their place in the world through their primary culture. From analysis of the transcripts, three themes emerged as important in participants' sense of professional success: (1) Maintaining Native American values of belonging, connectedness, and giving back was essential, (2) success was perceived and experienced to have changed over time, and (3) mentoring relationships made success possible. CONCLUSIONS: Native American women faculty based their identity and definition of success in their primary culture's values, relationships, and expectations. Academic success can be accomplished with mentorship that honors the Native American woman's responsibility to her culture over time (with clinical and academic opportunities) while also assisting with development of appropriate academic skills and opportunities. PMID- 20354389 TI - How, when, and why do physicians choose careers in academic medicine? A literature review. AB - PURPOSE: Medicine has different pathways in which physicians pursue their vocation. Clinical practice, research, and academia are common paths. The authors examined the literature to identify research-based factors influencing physicians to choose a career path in academic medicine. METHOD: In the fall of 2006, the authors searched the PubMed database from 1960 to 2006 using the term career academic medicine. Review of articles resulted in the identification of nine themes relating to academic medicine career paths. The authors summarized the important and relevant articles to capture what the literature contributed as a whole to the larger question, "How, when, and why do physicians choose an academic career in medicine?" RESULTS: A synthesis of articles revealed that (1) values are essential to understanding the decision to enter a career in academic medicine, (2) factors associated with academic medicine career choice include research-oriented programs, gender, and mentors and role models, (3) an obstacle to pursuing this career path is loss of interest in academic careers during residency as residents learn about factors associated with academic careers in medicine, and (4) debt may be a barrier to choosing an academic career in medicine for some individuals in some specialties. CONCLUSIONS: Despite the study findings, the larger question (stated above) remains essentially unanswered in the literature. The authors propose a call to action by various professional groups and organizations to use rigorous and complex research efforts to seek answers to this very important question. PMID- 20354390 TI - Perspective: PhD scientists completing medical school in two years: looking at the Miami PhD-to-MD program alumni twenty years later. AB - Producing and retaining physician-scientists remains a major challenge in advancing innovation, knowledge, and patient care across all medical disciplines. Various programs during medical school, including MD-PhD programs, have been instituted to address the need for continued production of physician-scientists. From 1971 through 1989, 508 students with a prior PhD in the sciences, mathematics, or engineering graduated in two years from an accelerated MD program at the University of Miami School of Medicine. The program, designed to address potential clinical physician shortages rather than physician-scientist shortages, quickly attracted many top-notch scientists to medicine. Many program graduates went to top-tier residencies, pursued research careers in academic medicine, and became academic leaders in their respective fields. A retrospective examination of graduates conducted in 2008-2009 demonstrated that approximately 59% took positions in academic university medical departments, 3% worked for governmental agencies, 5% entered industry as researchers or executives, and 33% opted for private practice. Graduates' positions included 85 full professors, 11 university directors or division heads, 14 academic chairs, 2 medical school deans, and 1 astronaut. Overall, 30% of graduates had obtained National Institutes of Health funding after completing the program. These results suggest that accelerated medical training for accomplished scientists can produce a large number of successful physician-scientists and other leaders in medicine. Furthermore, these results suggest that shortening the medical portion of combined MD-PhD programs might also be considered. PMID- 20354391 TI - Perspective: are we teaching racial profiling? The dangers of subjective determinations of race and ethnicity in case presentations. AB - Physicians make subjective visual assessments concerning the race and/or ethnicity of their patients and document these assessments in patient histories every day. Medical students learn this practice through textbooks and the example set by their educators. Although physicians may believe that they are helping their patients, the practice of using visual clues concerning race and/or ethnicity to determine whether a patient is at risk of certain diseases lacks scientific rigor and may put the patient at significant risk of receiving substandard medical care. The authors argue that if the patient's race or ethnicity is of critical importance, the data should be collected through more objective, scientifically rigorous means, such as genetic testing. In this article, the authors call for the widespread transformation of the way medical schools teach tomorrow's physicians about the role of race and ethnicity in taking medical histories, and they challenge physicians to change their current practices. PMID- 20354392 TI - Perspective: successfully negotiating the clerkship years of medical school: a guide for medical students, implications for residents and faculty. AB - Medical students face significant learning and cultural challenges during the transition from the classroom to the clinical setting. The authors recommend that students be proactive in preparing themselves for this difficult journey by understanding and applying principles of adult learning. To guide students in this preparation, the authors propose a model that incorporates adult learning principles into a cycle emphasizing reflective practice. This model, based on the Kolb learning cycle, consists of five sequential steps: (1) preparing for the clinical setting, (2) experiencing the clinical setting, (3) reflecting on experience, (4) conceptualizing new approaches, and (5) testing new approaches on return to the clinical setting. This fifth stage in the cycle completes the first iteration. The cycle never ends, however; experimentation leads to new reflection, which in turn leads to new approaches and new experience. PMID- 20354393 TI - Core clerkship directors: their current resources and the rewards of the role. AB - PURPOSE: To conduct a national multidisciplinary investigation assessing core clinical clerkships and their directors, variances in resources from national guidelines, and the impact of the clerkship director role on faculty members' academic productivity, advancement, and satisfaction. METHOD: A multidisciplinary working group of the Alliance for Clinical Education (ACE), representing all seven core clinical disciplines, created and distributed a survey to clerkship directors at 125 U.S. MD-granting medical schools, in academic year 2006-2007. RESULTS: A total of 544 clerkship directors from Internal Medicine (96), Family Medicine (91), Psychiatry, (91), Pediatrics (79), Surgery (71), Neurology (60), and Obstetrics-Gynecology (56) responded, representing over 60% of U.S. core clinical clerkships. The clerkship directors were similar across disciplines in demographics and academic productivity, though clinical and clerkship activities varied. Departmental staff support for clerkships averaged 0.69 people, distinctly less than the ACE's 2003 guideline of a full-time coordinator in all disciplines' clerkships. Clerkship directors reported heavy clinical responsibilities, which, as in previous studies, were negatively related to academic productivity. However, many clerkship directors felt the role enhanced their academic advancement; a large majority felt it significantly enhanced their career satisfaction. CONCLUSIONS: The resources and rewards of the clerkship director role were similar across disciplines. Expectations of clerkship directors were considerable, including responsibility for clinical material and the learning environment. Resources for many fall short of those stated in the ACE guidelines, particularly regarding support staff. However, the findings indicate that the clerkship director role can have benefits for academic advancement and strongly enhances career satisfaction. PMID- 20354394 TI - Multicenter trial of the clinical activities tool to document the comparability of clinical experiences in obstetrics-gynecology clerkships. AB - PURPOSE: To assess the implementation of the Clinical Activities Tool (CAT) for facilitating Liaison Committee on Medical Education-required documentation of the comparability of obstetrics-gynecology (ob/gyn) clinical experiences and midclerkship feedback at multiple sites during one academic year. METHOD: Ob/gyn clerkship students at six U.S. medical schools were given CATs to guide and document clinical experiences from June 2006 to June 2007. Students used a paper CAT at five institutions and an electronic version at one. CATs listed procedures, skills, and topics recommended by the Association of Professors of Gynecology and Obstetrics and included a midclerkship feedback section. Resident/faculty signatures documented completion of items for paper CATs. Electronic CAT item completion was self-documented by students. Students completed a questionnaire on CAT use. RESULTS: At the six schools, 876 medical students rotated on ob/gyn clerkships; 808 (92%) submitted CATs. Mean item completion rate was 72%. Five of six schools achieved >/=70% completion rates. Midclerkship feedback signature rates ranged from 0% to 97.8% with four of six schools reporting >/=65% feedback. Comparability of clinical experiences and midclerkship feedback was successfully documented across sites for each institution (number of sites: range = 1-9; median = 5). Questionnaires on CAT use were submitted by 231 students (26%). Students using paper CATs reported that doing so clarified course objectives (93%), provided clerkship guidance/structure (93%), and facilitated interaction with faculty/residents (76%/74%). Students rated the electronic CAT significantly less favorably. CONCLUSIONS: CAT implementation at multiple institutions for documentation of student clinical experience comparability and midclerkship feedback was successful. Students evaluated the paper CAT positively. PMID- 20354396 TI - Preventing and responding to complaints of sexual harassment in an academic health center: a 10-year review from the Medical University of South Carolina. AB - There is a high incidence of sexual harassment and gender discrimination in academic health center (AHC) settings according to multiple surveys of medical students. Therefore, it is incumbent on AHCs to develop programs both to educate faculty, residents, and students and to handle complaints of possible episodes of sexual harassment or gender discrimination. Despite the apparent high prevalence of gender discrimination and sexual harassment, and the importance of handling complaints of gender discrimination and sexual harassment in a prompt, consistent, and rational manner, there are few descriptions of programs that address those concerns in AHCs.Herein, the authors describe their experiences in dealing with complaints of sexual harassment and gender discrimination for a 10 year period of time (late 1997 to early 2007) at the Medical University of South Carolina, through an Office of Gender Equity. They describe their complaint process, components of their prevention training, and the outcomes of 115 complaints. Key elements of their policies are highlighted. The authors offer an approach that could serve as a model for other AHCs. PMID- 20354397 TI - Development of an interinstitutional collaboration to support community-partnered research addressing the health of emerging Latino populations. AB - Collaborative and participatory research approaches have received considerable attention as means to understanding and addressing disparities in health and health care. In this article, the authors describe the process of building a three-way partnership among two academic health centers-Duke University and the University of North Carolina-and members of the Latino community in North Carolina to develop and pilot test a lay health advisor program to improve Latina immigrants' mental health and coping skills. The authors applied the principles of participatory research to engage community and academic partners, to select the health topic and population, and to develop program goals and objectives. Key challenges were negotiating administrative structures and learning institutional cultures, as well as dealing with contextual issues such as mental health reform and antiimmigrant sentiment in the state.Some important lessons learned are to seek opportunities for taking advantage of existing relationships and expertise at each academic institution, to be respectful of the burden of research on vulnerable communities, and to involve community partners at all stages of the process. PMID- 20354399 TI - AM Last Page: practice characteristics of racial and ethnic minority graduates of U.S. MD-degree granting medical schools. PMID- 20354400 TI - Nursing satisfaction and Web-based competencies. AB - This article describes the study of nursing satisfaction with Web-based learning and competency assignment given the learning management system (LMS) change from one LMS to another in 1 year. An anonymous paper-pencil survey was distributed to nursing staff after completing a year with two LMSs and prior to assigning Web based competency requirements in the newer system (pre) and again after completing requirements (post). Nursing satisfaction and ease of use improved with assignment of requirements. Implications for staff development are described. PMID- 20354401 TI - Expectations, perceptions, and satisfaction of graduate nurses. AB - There is little research investigating the expectations and perceptions of graduate nurses. The purpose of this study was to investigate the expectations, perceptions, and satisfaction of graduate nurses. Individual interviews were performed at 1, 6, and 12 months. Results indicate that nurses were fairly satisfied, and two themes emerged: Establishing Relationships and Learning the Job. Findings contribute firsthand accounts of graduate experiences, which are valuable for staff development professionals creating programs to meet the needs of graduate nurses. PMID- 20354402 TI - Making the case: using case studies for staff development. AB - The case study is a popular teaching strategy frequently used in academic settings. Currently, little evidence is found to support hospital-based educators using case studies to promote enhanced problem-solving, decision-making, and critical-thinking abilities. Department orientation and the improvement of patient outcomes are two examples of the use of case studies discussed in this article. Criteria for choosing and implementing an effective case study also are reviewed. PMID- 20354404 TI - Challenges in healthcare education: a correlational study of outcomes using two learning techniques. AB - Electronic learning has become an important tool in today's changing healthcare environment. Institutions confronted with limited resources, in the face of increased demands for education and a shortage of educators, have found electronically based education a significant resource. This study compares electronic-blended instruction technique with instructor-led delivery of the same content and examines the correlation of learning effectiveness to each delivery method. PMID- 20354406 TI - The evaluation of a 12-month health service manager mentoring program in a corrections environment. AB - Mentoring programs are believed to positively influence the professional development of nurses where a system is provided to promote skill and knowledge base enhancement within a supportive relationship between mentor and mentee. This study aimed to evaluate a 12-month health manager mentoring program within a correctional facility in New South Wales, Australia. Over the period of the mentoring program, there was an improvement in professional behavior and a decline in the rating of supervisees. Work stress increased and job satisfaction decreased over the 12-month period, although not to a statistically significant level. Qualitative feedback suggested that participants found the program to be useful. PMID- 20354407 TI - Development and implementation of an independence rating scale and evaluation process for nursing orientation of new graduates. AB - A wide variety of evaluation formats are available for new graduate nurses, but most of them are single-point evaluation tools that do not provide a clear picture of progress for orientee or educator. This article describes the development of a Web-based evaluation tool that combines learning taxonomies with the Synergy model into a rating scale based on independent performance. The evaluation tool and process provides open 24/7 access to evaluation documentation for members of the orientation team, demystifying the process and clarifying expectations. The implementation of the tool has proven to be transformative in the perceptions of evaluation and performance expectations of new graduates. This tool has been successful at monitoring progress, altering education, and opening dialogue about performance for over 125 new graduate nurses since inception. PMID- 20354408 TI - Utilizing a mock trial to demonstrate evidence-based nursing practice: a staff development process. AB - In a healthcare environment, programs for staff development are essential. Continuing education promotes nursing competence and enhances a commitment to the profession. In this article, the authors illustrate the experience with a recent staff development initiative, describe lessons learned, and provide recommendations for future staff development programming. PMID- 20354409 TI - Night shift team building: an intervention to address the diverse needs of an underserved nursing population. PMID- 20354410 TI - American Nurses Association's code of ethics: an application. PMID- 20354411 TI - Preceptorship. PMID- 20354413 TI - Nursing professional development: stories, tips, and techniques. PMID- 20354414 TI - Perceived uncertainty, coping strategies, and adaptation in women with human papillomavirus on pap smear. AB - OBJECTIVE: To explore, identify, and describe the perception of uncertainty over time in college-aged women experiencing the unexpected event of an abnormal Pap smear with human papillomavirus (HPV). METHODS: Eighty-eight female patients, who had abnormal Pap smear and had indications for colposcopy, were recruited from a Student Health Service and consented for study participation. Uncertainty levels were measured over time. Relationships among uncertainty, knowledge of HPV, body attitude and moods, coping strategies, and follow-up were evaluated. RESULTS: The relationship between uncertainty and coping strategies was supported in the emotion-focused path as predicted but not in the problem-focused path. Evidence of adaptation to uncertainty through emotion-focused coping was found in the significant relationship between emotion-focused coping and body attitude. Similarly, there was a significant relationship between emotion-focused coping and moods in the path analysis and in correlations with the subcategories of positive and negative moods. The problem-focused indirect path from uncertainty to adaptation showed no significant relationship. Likewise, uncertainty also had no significant direct effect on body attitude or promptness of follow-up but did have a direct impact on moods. The direct path from previous knowledge to uncertainty was not supported. CONCLUSIONS: The presence of uncertainty over time was established in this study population. Statistically significant relationships were confirmed among uncertainty, emotion-focused coping strategies, and adaptation in a group of young women experiencing a mildly abnormal Pap smear. PMID- 20354415 TI - Anal-rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients. AB - OBJECTIVES: We describe the cytological distribution of disease, correlate cytological diagnoses with human papillomavirus (HPV) DNA status and surgical biopsy diagnoses, determine if CD4 counts correlate with lesion severity, and compare anal-rectal data of HIV-infected patients (primarily men) with cervical data. MATERIALS AND METHODS: A retrospective search of the computerized database identified 118 HIV-positive patients who had anal-rectal cytology. Cytology results were compared with available follow-up data including repeat anal-rectal cytology tests, surgical biopsy, CD4 counts, and HPV DNA polymerase chain reaction-based genotyping. RESULTS: Cytological diagnoses included 3% unsatisfactory for diagnosis, 41% negative for intraepithelial lesion or malignancy (NILM), 23% atypical squamous cells of undermined significance (ASC US), 31% low-grade squamous intraepithelial lesion (LSIL), and 2% high-grade squamous intraepithelial lesion (HSIL) (ASC-US/squamous intraepithelial lesion, 0.7:1). Two anal intraepithelial neoplasia (AIN) II, 10 AIN III, and 1 invasive squamous cell carcinoma were histologically detected (11%). The majority of AIN II was preceded by LSIL, 54%; ASC-US, 15%; and HSIL, 8%. The false-negative fraction was 23%. Sensitivity, specificity, negative predictive value, and positive predictive value were 92%, 8%, 33%, and 67%, respectively. Of those HPV tested concurrent with the first cytology specimen, 48% NILM, 78% ASC-US, and 100% LSIL were HPV positive. Mean CD4 counts (per microliter) were lower in patients with HSIL (243 [SD, 65]) compared with LSIL (400 [SD, 261]) and NILM (428 [SD, 232]). CONCLUSIONS: Anal-rectal cytology is a useful screening test. A high percentage of AIN II lesions were detected in this at-risk population, and the majority was detected following cytological abnormality. PMID- 20354416 TI - Lessons from practice: risk of CIN 3 or cancer associated with an LSIL or HPV positive ASC-US screening result in women aged 21 to 24. AB - OBJECTIVE: To characterize the risks of cervical intraepithelial neoplasia 3 (CIN 3) and cancer in women aged 21 to 24 with human papillomavirus (HPV)-positive atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) screening results in routine clinical practice. MATERIALS AND METHODS: Quality assurance databases containing records of screening test and histologic findings from the Regional Laboratory of the Northern California Kaiser Permanente Medical Care Program were reviewed. Numbers of LSIL and HPV-positive ASC-US results and associated cancers and CIN 3 in women aged 21 to 24 during 2003 to 2007 were tabulated, and the corresponding risks were calculated overall and by year of age. RESULTS: During the 5-year period from 2003 to 2007, 1,620 HPV-positive ASC-US and 2,175 LSIL were diagnosed in women aged 21 to 24, for which corresponding histologic finding is available. No invasive cancers were detected in association with LSIL and HPV-positive ASC-US screening results in this age group during this period. The risk of cancer was therefore 0% (95% CI = 0.00%-0.10%). The risk of CIN 3 associated with an HPV positive ASC-US was 2.90% (95% CI = 2.14%-3.84%), with LSIL was 2.44% (95% CI = 1.83%-3.18%), and, for the 2 combined, the risk was 2.64% (95% CI = 2.15%-3.20%). CONCLUSIONS: The risk of CIN 3 and cancer is low enough that management of women aged 21 to 24 with ASC-US and LSIL smears without immediate colposcopy should be considered, as is currently recommended for women aged 20 and younger. PMID- 20354417 TI - Assessment of the perceptions and administration of the human papillomavirus vaccine. AB - OBJECTIVES: To investigate practitioner acceptability of the recommendation to offer the human papillomavirus (HPV) vaccine to adolescent women. METHODS AND MATERIALS: After obtaining institutional review board approval, 1,336 Connecticut licensed pediatricians were contacted. A 16-question survey form was mailed, and responses received between January 20 and May 20, 2008, are reported. RESULTS: Of the 434 returned survey forms, 89 were not completed because the physicians were currently retired or practicing as subspecialists. Among the 345 valid survey forms, most pediatricians described their understanding about HPV as "moderately knowledgeable" (53.3%) or "very knowledgeable" (37.4%). There was a significant correlation between physician knowledge about HPV and willingness to discuss sexually transmitted infections (STIs; p < .001). Most pediatricians (91.0%) reported that they begin discussing STIs when their patients are between the ages of 10 and 16 years. More than 94% of pediatricians reported that they "always" or "sometimes" discuss the vaccine when discussing STIs. Pediatricians reported that 67% of patients agreed to receive the HPV vaccine. Reasons that 33% of parents choose not to have their children receive the vaccine include the unknown long term effects (71.1%) and the belief that their child is not sexually active (66.4%). Primary adverse effects cited by pediatricians include injection site burning (77.4%), with fewer reports of fainting (15.1%), dizziness (13.6%), fever (9.3%), and nausea/vomiting (2.3%). CONCLUSIONS: Pediatricians in Connecticut who claim to be knowledgeable about HPV are more likely to initiate discussions of STIs. Addressing parental concerns and discussing the primary adverse effects may alleviate anxiety associated with HPV vaccination and increase vaccine administration. PMID- 20354418 TI - Diagnostic reproducibility of cervical intraepithelial neoplasia 3 and atrophy in menopausal women on hematoxylin and eosin, Ki-67, and p16 stained slides. AB - OBJECTIVE: To establish diagnostic accuracy and reproducibility of a diagnosis of cervical intraepithelial neoplasia 3 (CIN 3) in menopausal women on routinely stained hematoxylin and eosin (H&E) slides and compare it to slides processed for p16 and Ki-67. MATERIALS AND METHODS: Confirmed cases of CIN 3 and benign atrophic changes were reviewed independently by 4 pathologists. The samples were studied on separate occasions using H&E staining, p16, and Ki-67. Differences in sensitivity and specificity between reviewers or methods were tested for significance using the McNemar test, whereas differences in positive and negative predictive values were tested for significance using a marginal probability generalized linear model for agreement. RESULTS: Sensitivity was high for H&E (93.3%-100%) and Ki-67 (93.3%-100%) and lower for p16 (70.0%-90.0%). Intraobserver variability was also lower for p16 (76.7% vs 90.0%, although this difference was not statistically significant, p = .219). p16 agreement, however, for CIN 3 is significantly lower than that for atrophy (76.7% vs 97.4%, p = .018). CONCLUSIONS: Routine histopathologic diagnosis of CIN 3 in menopausal women is highly accurate and reproducible. Both H&E and Ki-67 are useful immunohistochemical stains in helping differentiate atrophy from high-grade cervical intraepithelial lesions in postmenopausal cervical biopsies. There may be more disagreement among readers using p16. PMID- 20354419 TI - Knowledge and attitudes of adult peruvian women vis-a-vis Human Papillomavirus (HPV), cervical cancer, and the HPV vaccine. AB - OBJECTIVES: To determine knowledge and attitudes of adult Peruvian women regarding the human papillomavirus (HPV), cervical cancer, and acceptability of the HPV vaccine. METHODS: A 4-section survey was administered to 511 25- to 65 year-old Peruvian women living in 3 low-income districts in Lima. RESULTS: Knowledge of HPV, the HPV vaccine, cervical cancer, and the association between HPV and cervical cancer was low. Approximately two-thirds of the participants knew nothing about HPV, the vaccine, and cervical cancer. However, vaccine acceptability was very high: 90% indicated they would get vaccinated if the HPV vaccine was available. In addition, 58% of the population was willing to pay "something," versus nothing, to be vaccinated. CONCLUSIONS: Although their knowledge was limited, mid adult Peruvian women have a very high level of acceptance for the HPV vaccine. Efforts to educate the population about HPV and cervical cancer are warranted along with further studies exploring the reasons for high vaccination acceptability to help reduce the rate of cervical cancer. PMID- 20354420 TI - Lichen sclerosus: treatment and follow-up at the departments of gynaecology and dermatology. AB - OBJECTIVE: To compare the treatment and follow-up of patients with lichen sclerosus (LS) at the departments of Gynaecology and Dermatology at the Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands, to evaluate the need for a multidisciplinary vulvar clinic. MATERIALS AND METHODS: Treatment and follow-up data of all women with histologically proven (between January 1995 and January 2001) anogenital LS visiting the outpatient clinics of the departments of Obstetrics & Gynaecology and Dermatology were collected (last date of follow-up: January 2008). RESULTS: Eighty-four patients with LS were included in this study, 10 patients (12%) of which were treated by both specialties. At the Gynaecology department, LS patients more often received surgical treatment, topical estrogens, and lidocaine ointment, whereas at the Dermatology department, local class 2/3 corticosteroids were more often prescribed. Follow-up frequencies were similar in both specialties and took place at 3 to 4 visits in the first year and at least once a year afterward. One patient developed vulvar squamous cell carcinoma. This patient had withdrawn from follow-up and had her condition diagnosed with carcinoma 74 months after the LS had been diagnosed. CONCLUSIONS: Although no hospital guidelines existed, management of patients with LS agreed with current recommendations in the literature, although differences in secondary and supportive therapy existed owing to differences in expertise. The relatively high percentage of patients treated by both specialties with a high frequency of visits emphasizes the need for a multidisciplinary clinic for vulvar disease. PMID- 20354421 TI - A favorable clinical trend is associated with CD8 T-cell immune responses to the human papillomavirus type 16 e6 antigens in women being studied for abnormal pap smear results. AB - OBJECTIVE: The goal of this study was to examine the role of CD8 T-cell responses to human papillomavirus type 16 (HPV-16) in a favorable clinical trend in women being studied for abnormal Pap smear results. MATERIALS AND METHODS: Human papillomavirus-deoxyribonucleic acid testing and enzyme-linked immunospot assay using the HPV-16 E6 and E7 antigens were performed. The subjects with subsequent normal histologic diagnoses were considered to be "regressors" (n = 28), whereas those with histologic diagnoses of cervical intraepithelial neoplasia 1, 2, or 3 were considered to have short-term persistence of cervical abnormality and were designated to be "persistors" (n = 37). RESULTS: There was a higher percentage of CD8 T-cell responses to the E6 antigen in the regressors (15/28 or 53.6%) when compared with the persistors (10/37 or 27.0%; p = .04), but there was no recorded response difference for the E7 antigen. Results were the same when the analyses for E6 included only subjects who were high-risk HPV-positive (p = .01). CONCLUSIONS: The CD8 T-cell immune responses to the HPV-16 E6 antigens but not to E7 antigens are associated with a favorable clinical trend regardless of HPV types currently detected. PMID- 20354422 TI - Cervical conization complicated by sepsis with lung and liver abscesses. AB - BACKGROUND: Extrapelvic infections complicating cervical conization are exceedingly rare. CASE: Seven days after conization, a 44-year-old patient presented with fever and right upper quadrant pain. Pleural effusion and pulmonary and hepatic abscesses were detected. The pathology report of the conization showed microabscesses. Blood cultures grew Fusobacterium necrophorum. Intravenous antibiotics were administered. The pulmonary findings improved but did not completely resolve after drainage of pleural effusions. The patient refused further procedures and was discharged in good clinical condition and with oral antibiotics after 37 days. CONCLUSIONS: Extrapelvic abscesses are rare complications of cervical conization. This is the first report in identifying F. necrophorum as a cause of this complication. Appropriate cultures, drainage of abscesses, and antibiotics are the mainstay of diagnosis and treatment. PMID- 20354423 TI - An immunocompromised woman with severe molluscum contagiosum that responded well to topical imiquimod: a case report and literature review. AB - Molluscum contagiosum is a common condition that often occurs in children, sexually active young adults, and immunocompromised patients. Generally, molluscum contagiosum lesions are self-limited. They often resolve spontaneously. We report a severe case of genital molluscum contagiosum in a patient with Sjogren syndrome. Her vulvar lesions responded to topical 5% imiquimod cream. PMID- 20354424 TI - Myeloid sarcoma of the vagina: a report of 2 cases. AB - OBJECTIVE: To describe 2 cases of myeloid sarcoma of the vagina, in a patient without a history of acute myeloid leukemia (AML) and in another whose condition was previously diagnosed with AML. MATERIALS AND METHODS: The clinical histories of 2 patients whose conditions were diagnosed with myeloid sarcoma of the vagina were obtained from their medical records. RESULTS: Case 1: A 77-year-old woman with no systemic illnesses presented with a vaginal lump. Clinically, there was a 6-cm periurethral mass that was examined by biopsy. The histopathologic specimen was evaluated on routine and immunohistochemical stains, and myeloid sarcoma was diagnosed after extensive immunohistochemical analysis. The patient was treated with pelvic radiation. She developed extensive myeloid sarcoma of the skin and AML 4.5 months later; she died 2 weeks later, 5 months after the initial presentation. Case 2: A 36-year-old woman with a known history of AML who has had multiple leukemic and extramedullary recurrences presented with a pelvic mass. Physical findings revealed large masses in the vagina and rectovaginal septum, which were confirmed as myeloid sarcoma after biopsy and histologic examination. The patient was treated with pelvic/vaginal radiation. Five months later, she had another leukemic relapse and died within 1 day of palliative chemotherapy. CONCLUSIONS: Myeloid sarcoma of the vagina is extremely rare. Most patients have a poor prognosis and either have a history of or will subsequently develop AML. PMID- 20354425 TI - Cervical neoplasia guidelines: United States and europe compared. PMID- 20354426 TI - Complications of abdominal contouring surgery in obese patients: current status. AB - Medical records of 122 patients who underwent an abdominoplasty or panniculectomy from 2003 to 2008 were reviewed to determine current rates of wound complications associated with these procedures in the presence of obesity. An additional aim was to determine current rates of complications as compared with those found 10 years ago at our institution to determine if the finding of obesity alone continues to adversely affect wound outcomes. Sixty-three of 122 patients (51.6%) experienced 1 or more wound-related complications. Major complications occurred in 13 patients (10.7%). A striking finding was that the lowest major complication rate 4.5%, was found in patients with extreme obesity (BMI >40). Comparisons between the 1999 and current studies found that the difference in major complications in those classified as obese, with 2 (9%) in the current study and 8 (40%) in the 1999 study, was significant (P = 0.039). Our findings suggest that high rates of major complications found in those with obesity in the 1999 study are not found today. Extreme obesity is not an absolute contraindication to operation and may be performed safely. PMID- 20354427 TI - Association between preoperative measurements and resection weight in patients undergoing reduction mammaplasty. AB - Current guidelines used to predict appropriate resection weight for patients undergoing reduction mammaplasty are typically based on relatively nondescript patient characteristics and are most often inaccurate. The determination of patient measurements that correlate with resection weight could enable appropriate resection weight to be predicted more precisely and on an individualized basis. To better elucidate this, data from 348 patients undergoing bilateral reduction mammaplasty (696 breasts) between October 2001 and March 2009 were reviewed retrospectively. The association between resection weight and sternal notch to nipple distance (SNN), inframammary fold to nipple distance (IMFN), and body mass index (BMI) was assessed. Regression analysis demonstrated a strong correlation between resection weight and SNN distance (r = 0.672, P < 0.001), IMFN distance (r = 0.467, P < 0.001), and BMI (r = 0.510, P < 0.001). The strongest correlation was observed after incorporating all 3 parameters (r = 0.740, P < 0.001). This enabled the calculation of a formula to predict resection weight: Predicted weight = 40.0(SNN) + 24.7(IMFN) + 17.7(BMI) - 1443 In conclusion, resection weight correlates strongly with SNN, IMFN, and BMI in patients undergoing reduction mammaplasty. When considered together, resection weight can be predicted with a strong degree of accuracy. PMID- 20354428 TI - Is reduction mammaplasty a stimulus for weight loss and improved quality of life? AB - Reducing breast size for women with macromastia does more than provide symptomatic relief. The purpose of this study was to evaluate whether reduction mammaplasty was felt to be a stimulus for postoperative weight loss, subjective glucose control, and improved self-confidence. All patients who underwent reduction mammaplasty at Emory University Hospital by the senior author were reviewed. Patient demographics were queried, and a standardized questionnaire was devised to obtain information regarding postoperative weight, dress size, glucose control, and exercise. Forty-one women participated in the questionnaire. Mean follow-up was 2 years (range, 1-6). Patients were stratified according to whether they felt reduction mammaplasty was a stimulus for future weight loss; 63% stated yes (group A), 37% responded no (group B). Group A had significant postoperative weight loss (P < 0.001) and decreased dress size (P < 0.001). Group B had no change in weight (P = 0.239) or dress size (P = 0.735). There was 100% improvement of patient reported postoperative glucose control in group A and 50% improvement in group B. Sexual activity was improved in 85% of women in group A, and only 40% in group B. Group A patients had significantly increased postoperative exercise (P < 0.001); group B had no change. Reduction mammaplasty in motivated patients may be a stimulus for postoperative weight loss, and those patients were more physically active, had better glucose control and had an improved self-confidence. PMID- 20354429 TI - The pectoralis major myocutaneous flap revisited: a reliable technique for head and neck reconstruction. AB - The pectoralis major myocutaneous flap (PMMF) remains a useful flap for head and neck reconstruction. Although free-tissue transfer is often preferred, the benefits of the PMMF should not be overlooked. A retrospective chart review was performed on all PMMFs used at Emory for head and neck reconstruction from 1992 through 2008. A total of 139 PMMF were performed in 136 patients with an average age of 65 years. Eighty-six patients were males. All patients except one had a history of Head and Neck Cancer. A smoking history was present in 92% of the patients. Defect location included oral cavity (n = 59), pharyngeal/fistulae (n = 48), temporal bone and cheek (n = 24), oropharyngeal (n = 4), and esophageal (n = 2). The PMMF was used in 4 occasions as a salvage procedure. The survival of the flap was 99.2% (138/139). The PMMF provided definitive closure of the defect in 100% of the cases. The overall average follow-up was 10.5 months. Eighteen patients (13%) developed complications after the procedure. Patients who had radiation therapy had significantly higher complication rates. The PMMF flap remains a very versatile technique with proven reliability for soft tissue coverage of many head and neck defects. PMID- 20354430 TI - Breastfeeding after augmentation mammaplasty with saline implants. AB - It has been reported that breastfeeding problems occur in women who have breast implants. The breastfeeding success of women who had augmentation with saline implants and subsequently had a live birth (n = 107) was compared with that of women of similar age who had hypoplastic breasts and had children before their consultation (n = 105). A self-administered 11-item questionnaire was used to collect data on demographics and breastfeeding success. The information requested included age, weight, height, whether breastfeeding was attempted, if it was successful, and the need to supplement. Additional information requested from the study group included position of breast scar, implant volume, and whether loss of nipple sensation had occurred after the surgery (as judged by the patient). The groups were not significantly different in age (22 +/- 7 vs. 23 +/- 5). There was, however, a significant difference (P < 0.05) in the breastfeeding success and need to supplement feedings. Successful breastfeeding occurred in 88% of the control and 63% of the study group. A need to supplement breastfeeding occurred in 27% of the control group but increased to 46% in the study group. No significant difference (P > 0.05) was found in the breastfeeding experience between periareolar and inframammary approaches. Loss of nipple sensation after augmentation mammaplasty was reported by 2% of both the periareolar and inframammary subgroups. The success rate of breastfeeding decreases approximately 25% and the need to supplement breastfeeding increases 19% in young women with hypoplastic breasts after augmentation mammaplasty, irrespective of whether a periareolar or inframammary approach is used. PMID- 20354431 TI - An outcome analysis of brachioplasty techniques following massive weight loss. AB - Body contouring following massive weight loss (MWL) has gained in popularity. The demand for upper arm contouring procedures has increased, and we elected to evaluate our results, complications, and patient satisfaction with brachioplasty techniques in MWL patients. A retrospective review was performed on all patients who underwent a brachioplasty procedure. Patient demographics and risk factors were queried. We evaluated surgical techniques and outcomes. Thirty-one patients underwent a bilateral brachioplasty, with an average follow-up of 16 months. The surgical technique included double ellipse n = 16, and L-shaped n = 15. The average weight loss before the procedure was 146 pounds, and the average body mass index at the time of the surgery was 30. Risk factors were present in 68% of the patients. The complication rate was 22%, including cellulitis, hematoma, infection, delayed healing, and lymphocele. The revision rate was 16%, most being minor scar revisions for contour improvement. Patient satisfaction scores included overall satisfaction 4.3/5, contour improvement 4.3/5, symptomatic improvement 4.9/5, and scar appearance 3.9/5. Most patients (94%) reported improved self-esteem, 94% being more comfortable wearing short sleeve shirts, and 94% would undergo the procedure again. Brachioplasty is a relatively safe and effective procedure for upper body contouring in the MWL patient. Complications are minor, and small revisions in contour are not uncommon. Patients report improvement in contour and self-esteem, and a high level of satisfaction with this procedure, despite the potential for an unfavorable scar. PMID- 20354432 TI - Skin tightening with fractional lasers, radiofrequency, Smartlipo. AB - Skin tightening occurs with the use of fractional lasers, radiofrequency, and Smartlipo. The fractional lasers Fraxel (1550 nm; Solta Medical, Inc., Hayward, CA) and Affirm (1440 nm, 1320 nm) (Cynosure, Westford, MA) when used in combination tighten skin and lessen solar keratoses, and improve acne scars. With radiofrequency, further tightening occurs. Smartlipo (Cynosure, Westford, MA) (1064 nm or the newer MPX with combined 1064 nm and 1320 nm) results in skin tightening and has been very helpful in improving skin tightness and smoothness on the neck either singularly or in combination with the above procedures; and with the addition of the Affirm fractional CO2 laser (Cynosure, Westford, MA), further skin improvement and tightening occurs. PMID- 20354433 TI - What are patients' goals and concerns about breast reconstruction after mastectomy? AB - Discussions about breast reconstruction should include factual information and consideration of the patient's personal concerns. Providers are familiar with the relevant facts but may not know which personal concerns are important to patients. Experience with breast cancer patients has found that providers frequently do not know their patients' treatment preferences. To help reconstructive surgeons discuss personal preferences with their patients, we sought to identify women's key concerns related to breast reconstruction. We employed a qualitative design and convened a sample of 65 women in 7 focus groups and 15 semi-structured interviews. Women with a recent history of early-stage breast cancer who had a mastectomy with or without reconstruction were included. A variety of backgrounds, including underserved populations, low education levels, and various ages were represented. Qualitative content analysis was performed, and key themes were identified. Five key themes emerged. (1) Magnitude of surgery and recovery. Many women reported that concerns over the number of operations, duration of recovery, and risk of complications strongly affected their decision-making. (2) Using one's own tissue. Several women felt comforted by the notion of using their own tissue for reconstruction. (3) Looking natural in clothing. Many women pointed out the difference between how they look in clothing versus how they look naked. (4) Avoiding an external prosthesis. Several women stressed practical concerns and framed the reconstruction decision in terms of not having to use prosthesis. (5) Considering others' opinions. A few women reported that their partners' opinion strongly influenced their decision. Many women stated that they ultimately followed their doctor's recommendation. Women considering reconstruction have some unmet emotional and physical needs as well as important goals and concerns that can affect their decisions about and experience with reconstruction. In particular, some breast cancer patients are unprepared for the full effect of surgery on their lives and for the recovery process. Discussions about reconstruction would benefit from inclusion of these key concerns. PMID- 20354434 TI - Breast ptosis: causes and cure. AB - Breast ptosis is one of the most common conditions treated by plastic surgeons, but the causes are not clearly defined. A review was conducted of 132 consecutive patients presenting for breast augmentation or mastopexy. Information was obtained by chart review and telephone interview. Standardized photographs were examined to determine degree of ptosis by the Regnault classification. Of patients who had at least one pregnancy, 85% reported adverse changes in breast shape following pregnancy, 35% reported a reduction in breast size, and 30% reported an increase in size. Upon logistic regression, age, history of significant (>50 lbs) weight loss, higher body mass index, larger bra cup size, number of pregnancies, and smoking history were found to be significant risk factors for breast ptosis (P < 0.05). History of breast-feeding, weight gain during pregnancy, and lack of participation in regular upper body exercise were not found to be significant risk factors for ptosis. PMID- 20354435 TI - Colloid osmotic pressure and the formation of posttraumatic cerebral edema. PMID- 20354436 TI - Implicit memory formation during routine anesthesia in children: a double-masked randomized controlled trial. AB - BACKGROUND: Implicit memory cannot be consciously recalled but may be revealed by changes in behavior. There is evidence for implicit memory formation during anesthesia in adults, but several studies in children have found no evidence for implicit memory. This may be due to insensitive testing. Also many of these tests were undertaken under controlled conditions. It remains unknown whether implicit memory is formed during routine pediatric anesthesia. The aim of this study was to determine whether there is evidence of implicit memory formation during routine anesthesia in children, using a degraded auditory stimulus recognition task. METHODS: Three hundred and twelve children, aged 5-12 yr, were randomly assigned to be played either a sheep sound or white noise continuously through headphones during general anesthesia. No attempt was made to standardize the anesthetic. On recovery, children were played a sheep sound degraded by a white noise mask that progressively decreased over 60 s, with the outcome being the time taken to correctly recognize the sheep sound. RESULTS: Three hundred children completed the task. A comparison of the distribution of recognition times between the two groups found little evidence that exposure to a sheep sound during anesthesia was associated with postoperative time to recognition of a degraded sheep sound (hazard ratio 1.14, 95% CI of 0.90-1.43, P = 0.28). CONCLUSION: No implicit memory formation during routine anesthesia was demonstrated in children. It is increasingly likely that the potential clinical implications of implicit memory formation are less of a concern for pediatric anesthetists. PMID- 20354437 TI - Eyes to the needle: to assist identification of the epidural space. PMID- 20354438 TI - KBG syndrome associated with periventricular nodular heterotopia. PMID- 20354439 TI - Distal trisomy 10q syndrome: phenotypic features in a child with inverted duplicated 10q25.1-q26.3. PMID- 20354440 TI - Prediction of cardiovascular mortality in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. AB - OBJECTIVES: We analyzed a large patient group to develop a clinical risk score that could be applied to patients after primary percutaneous coronary intervention (PCI). METHODS: We reviewed 2529 consecutive patients treated with primary PCI for ST-elevation myocardial infarction between 2003 and 2008. All clinical, angiographic and follow-up data were retrospectively collected. Independent predictors of in-hospital cardiovascular mortality were determined by multivariate Cox regression analysis in all study patients. RESULTS: Five variables (Killip class 2/3, unsuccessful procedure, contrast-induced nephropathy, diabetes mellitus, and age >70 years) were selected from the initial multivariate model. Each of them was weighted with 1 point according to their respective odds ratio for in-hospital mortality and then total risk score was calculated for each patient with a range of 0-5 points. For simplicity, four strata of risk were defined (low risk, score 0; intermediate risk, score 1; high risk, score 2 and very high risk, score > or =3). Each risk strata had a strong association with in-hospital cardiovascular mortality (P<0.001 for trend). Moreover, among survivors after an in-hospital period, our risk score continued to be a powerful predictor of long-term mortality (P<0.001 for trend). CONCLUSION: In patients treated with primary PCI, a risk score, which was developed from five risk factors readily available after intervention, may be useful to predict in-hospital and long-term cardiovascular mortality. PMID- 20354441 TI - Cardiovascular risk scores in the prediction of subclinical atherosclerosis in young adults: evidence from the cardiovascular risk in a young Finns study. AB - AIM: To study the utility of risk scores in the prediction of subclinical atherosclerosis in young adults. METHODS AND RESULTS: Participants were 2204 healthy Finnish adults aged 24-39 years in 2001 from a population-based follow-up study Cardiovascular Risk in Young Finns. We examined the performance of the Framingham, Reynolds, Systematic Coronary Risk Evaluation (SCORE), PROCAM, and Finrisk cardiovascular risk scores to predict subclinical atherosclerosis, that is carotid artery intima-media thickness (IMT) and plaque, carotid artery distensibility (CDist), and brachial artery flow-mediated dilatation (FMD) 6 years later. In a 6-year prediction of high IMT (highest decile or plaque), areas under the receiver operating characteristic curves (AUC) for baseline Finrisk (0.733), SCORE (0.726), PROCAM (0.712), and Reynolds (0.729) risk scores were similar as for Framingham risk score (0.728, P always >=0.15). All risk scores had a similar discrimination in predicting low CDist (lowest decile) (0.652, 0.642, 0.639, 0.658, 0.652 respectively, P always >=0.41). In the prediction of low FMD (lowest decile), Finrisk, PROCAM, Reynolds, and Framingham scores had similar AUCs (0.578, 0.594, 0.582, 0.568, P always >=0.08) and SCORE discriminated slightly better (AUC=0.596, P<0.05). The prediction of subclinical outcomes was consistent when estimated from other statistical measures of discrimination, reclassification, and calibration. CONCLUSION: Cardiovascular disease risk scores had equal value in predicting subclinical atherosclerosis measured by IMT and CDist in young adults. SCORE was more accurate in predicting low FMD than Framingham risk score. PMID- 20354442 TI - Helicobacter pylori resistance to metronidazole and clarithromycin in Ireland. AB - INTRODUCTION: Helicobacter pylori eradication rates have fallen considerably in recent years. Antibiotic resistance is thought to be rising. OBJECTIVES: To examine the levels of resistance to metronidazole (MTZ) and clarithromycin (CLA) in H. pylori, isolates were taken in a reference centre in Ireland from 2007 to 2008 and were compared to a similar cohort from a study in 1997. METHOD: Antimicrobial susceptibilities were tested by E-test. Frequencies of spontaneous metronidazole and clarithromycin resistance were measured on an agar plate containing the antibiotics at concentrations of 2x and 4x minimum inhibition concentration values. Clinical data were obtained from charts, laboratory and endoscopy reports. RESULTS: Two hundred and twenty-two patients were analyzed, 98 were females. Colonies amenable to culture were grown in 219 patients. Thirty seven had prior attempts at eradication therapy (all with amoxicillin-CLA-proton pump inhibitor. A total of 31.5% of the patients had strains resistant to MTZ and 13.2% of the patients were noted to have strains resistant to CLA. About 8.6% of the patients had strains resistant to both the agents. CLA resistance was 9.3% in those who had no prior eradication therapy compared with 32.4% of those who had. CLA resistance increased from 3.9%, among treatment-naive patients in 1997, to 9.3% in our study. MTZ resistance was 29.1% in the treatment-naive population. In 1997, MTZ resistance in the treatment-naive cohort was 27.1%. MTZ resistance was more likely to occur in females (35.4 vs. 28.5%) than in males. CONCLUSION: This study shows that resistance to CLA among Irish patients infected with H. pylori has increased since 1997. The future of treatment may well lie in the widespread use of sensitivity testing before the treatment. This would promote an accurate treatment. PMID- 20354443 TI - Quality of life in patients with spinal cord injury. AB - The primary objective of this study was to assess the quality of life (QoL) in spinal cord injury (SCI) survivors. Secondary objectives were to determine the effects of various sociodemographic and clinical characteristics on QoL. This cross-sectional study included 54 patients with SCI. The Turkish version of the Short-Form-36 Health Survey was used to assess health-related QoL. Functional status was measured with Functional Independence Measure. Higher values were obtained in younger individuals for bodily pain, in paraplegic patients for physical functioning, role-physical, social functioning, and role-emotional. Moreover, it was observed that functional status correlated well with physical functioning, role-physical, social functioning, and role-emotional. Among the complications investigated, bladder incontinence is related to low health-related QoL in most domains. SCI may interfere with some health domains of QoL according to the patient's age, neurologic levels, functional status and presence of complications, mainly bladder incontinence. PMID- 20354446 TI - High-dose vitamin C treatment reduces capillary leakage after burn plasma transfer in rats. AB - Oxidative stress after burn injuries leads to systemic capillary leakage and leukocyte activation. This study evaluates whether antioxidative treatment with high-dose vitamin C leads to burn edema reduction and prevention of leukocyte activation after burn plasma transfer. Donor rats underwent a burn (n = 7; 100 degrees C water, 12 seconds, 30% body surface area) or sham burn (37 degrees C water; n = 2) procedure and were killed after 4 hours for plasma harvest. This plasma was administered to study rats (continuous infusion). Rats were randomized to four groups (n = 8 each; burn plasma alone [BP]; burn plasma/vitamin C-bolus 66 mg/kg and maintenance dose 33 mg/kg/hr [VC66]; burn plasma/vitamin C-bolus 33 mg/kg and maintenance dose 17.5 mg/kg/hr [VC33]; and sham burn plasma [SB]). Intravital fluorescence microscopy in the mesentery was performed at 0, 60, and 120 minutes for microhemodynamic parameters, leukocyte adherence, and fluorescein isothiocyanate-albumin extravasation. No differences were observed in microhemodynamics at any time. Burn plasma induced capillary leakage, which was significantly higher compared with sham burn controls (P < .001). VC66 treatment reduced microvascular barrier dysfunction to sham burn levels, whereas VC33 had no significant effect. Leukocyte sticking increased after burn plasma infusion, which was not found for sham burn. Vitamin C treatment did not influence leukocyte activation (P > .05). Burn plasma transfer leads to systemic capillary leakage. High-dose vitamin C treatment (bolus 66 mg/kg and maintenance dose 33 mg/kg/hr) reduces endothelial damage to sham burn levels, whereas half the dose is inefficient. Leukocyte activation is not influenced by antioxidative treatment. Therefore, capillary leakage seems to be independent from leukocyte endothelial interactions after burn plasma transfer. High-dose vitamin C should be considered for parenteral treatment in every burn patient. PMID- 20354445 TI - Effects of exercise training on resting energy expenditure and lean mass during pediatric burn rehabilitation. AB - Severe burns cause profound hormonal and metabolic disturbances resulting in hypermetabolism, reflected in extreme elevation of resting energy expenditure (REE) and extensive skeletal muscle catabolism. Aerobic and resistive exercise programs during rehabilitation have shown substantial benefits, although whether such training potentially exacerbates basal metabolism is unknown. Therefore, the effects of exercise training on REE during the rehabilitation of severely burned pediatric patients were examined. Children with 40% total body surface area burns and greater were enrolled at admission to the burn intensive care unit to participate in a 12-week, hospital-based exercise program (EX) or a home-based standard of care program (SOC), commencing 6 months after injury. Twenty-one patients (aged 7-17 years) were enrolled and randomized to SOC (n = 10) or EX (n = 11). Age, sex, and total body surface area burned were similar. Mean change (+/ standard deviation) in REE, normalized to individual lean body mass, was almost negligible between SOC and EX group patients (SOC, 0.03 +/- 17.40% vs EX, 0.01 +/ 26.38%). A significant increase in lean body mass was found for EX patients (SOC, 2.06 +/- 3.17% vs EX, 8.75 +/- 5.65%; P = .004), which persisted when normalized to height (SOC, 0.70 +/- 2.39% vs EX, 6.14 +/- 6.46%; P = .02). Peak torque also improved significantly more in EX patients (SOC, 12.29 +/- 16.49% vs EX, 54.31 +/- 44.25%; P = .02), reflecting improved strength. Exercise training significantly enhanced lean mass and strength, without observed exacerbation of postburn hypermetabolism. Therefore, the use of exercise conditioning as a safe and effective component of pediatric burn rehabilitation is advocated. PMID- 20354447 TI - Compression neuropathy: a late finding in the postburn population: a four-year institutional review. AB - Nerve compression syndromes may cause postburn morbidity that can often be difficult to recognize and manage. This study reviewed patients in the authors' institution who needed nerve decompression secondary to thermal or electrical burns. The objective was to evaluate the timing of nerve decompression in the burn population. A 4-year review of the authors' institution's database found 22 patients who underwent peripheral neuroplasty. This patient population included both thermal and electrical burn patients. Two patients were excluded from the study because they underwent rapid forearm amputation, and a third patient who had his initial burn care done in Europe was also excluded. The authors reviewed the mechanism of burn: percentage of body surface area burned, which nerves underwent decompression, and time from burn to decompression. Nerve compression syndromes were diagnosed and treated in this group of patients from day 46 to 1530 post-burn. Carpal tunnel was the most common site of compression accounting for 46% of the nerve decompressions. Sixteen of the 19 (84%) patients required that synchronous nerves be decompressed. The average body surface area burn in the thermal group was 43 and 5% in the electrical burn group. Nerve compression syndromes secondary to burns can be a challenging problem to diagnose and treat. Multiple studies have shown the importance of treating nerve compressions in the acute setting; however, this study shows the importance of long-term surveillance, secondary to the late presentation of nerve compression syndromes. Late nerve compression neuropathies were present in both the electrical and thermal burn patients. The authors also found that presentation of a single nerve compression should raise the suspicion of a synchronous nerve compression. Patients with thermal burns greater than 20% body surface area and electrical burns should be routinely questioned and examined for the peripheral nerve compression syndromes during long-term follow-up. PMID- 20354444 TI - Results of the NIMH collaborative HIV/sexually transmitted disease prevention trial of a community popular opinion leader intervention. AB - OBJECTIVE: To determine whether community populations in community popular opinion leader intervention venues showed greater reductions in sexual risk practices and lower HIV/sexually transmitted disease (STD) incidence than those in comparison venues. METHODS: A 5-country group-randomized trial, conducted from 2002 to 2007, enrolled cohorts from 20 to 40 venues in each country. Venues, matched within country on sexual risk and other factors, were randomly assigned within matched pairs to the community popular opinion leader intervention or an AIDS education comparison. All participants had access to condoms and were assessed with repeated in-depth sexual behavior interviews, STD/HIV testing and treatment, and HIV/STD risk-reduction counseling. Sexual behavior change and HIV/STD incidence were measured over 2 years. RESULTS: Both intervention and comparison conditions showed declines of approximately 33% in risk behavior prevalence and had comparable diseases incidence within and across countries. CONCLUSIONS: The community-level intervention did not produce greater behavioral risk and disease incidence reduction than the comparison condition, perhaps due to the intensive prevention services received by all participants during the assessment. Repeated detailed self-review of risk behavior practices coupled with HIV/STD testing, treatment, HIV risk-reduction counseling, and condom access can themselves substantially change behavior and disease acquisition. PMID- 20354448 TI - Effects of fluid resuscitation methods on the pro- and anti-inflammatory cytokines and expression of adhesion molecules after burn injury. AB - Fluid resuscitation management can influence inflammatory response after burn injury. The aim of this study was to analyze the effects of two fluid resuscitation methods on the cytokine production and on the expression of the leukocyte surface markers. Thirty patients were included in this prospective randomized study with burn injury affecting more than 20% of the body surface area. Fluid resuscitation was guided by hourly urine output (HUO, n = 15) or by intrathoracic blood volume index (ITBVI, n = 15). Blood samples were taken on admission and on the next five consecutive mornings. Concentrations of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor alpha were measured in phorbol myristate acetate-stimulated and -nonstimulated samples. Leukocyte surface marker expressions (CD11a, CD11b, CD14, CD18, CD49d, and CD97) were also determined. In the ITBVI group, IL-6 levels on days 2 to 3 and IL-6/IL-10 ratios on days 2 to 3, and the IL-8/IL-10 ratios on days 3 to 5 were significantly higher than those in HUO group (P < .05). In the HUO group, IL 10 levels were significantly higher (P < .05) on days 4 and 5. Granulocyte CD11a levels on day 2, CD11b levels on days 4 to 6, lymphocyte CD11a on days 5 to 6, CD11b on days 3 to 6, CD49d on days 2 to 6, CD97 on day 6, monocyte CD11a, CD11b, CD18 levels on days 4 to 6, and CD14 levels on days 3 to 5 were significantly higher in the HUO group (P < .05). Our study suggests that ITBVI-guided fluid resuscitation of burned patients suppresses the shift toward anti-inflammatory imbalance and the expression of leukocyte surface markers more than HUO-guided resuscitation. PMID- 20354449 TI - Mucopolysaccharidosis type II: skeletal-muscle system involvement. AB - Mucopolysaccharidosis type II (MPS-II) is a rare lysosomal storage disorder caused by deficiency in the activity of the enzyme iduronate-2-sulphatase. This enzyme is responsible for the catabolism of two different glycosaminoglycans (GAGs), dermatan sulfate and heparan sulfate. Lysosomal accumulation of these GAG molecules results in cell, tissue, and organ dysfunction. The skeletal-muscle system involvement is because of essential accumulated GAGs in joints and connective tissue. MPS-II has many clinical features and includes two recognized clinical entities, mild and severe, that represent two ends of a wide spectrum of clinical severity. The aim of this study is to review the involvement of the skeletal-muscle system in MPS-II. PMID- 20354450 TI - Maintenance therapy in advanced non-small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world, and survival rates for advanced disease remain low with standard platinum-based chemotherapy. One treatment strategy that has been investigated extensively in NSCLC is that of "maintenance" therapy. Options for maintenance include maintaining response to initial therapy by continuing the initial combination chemotherapy regimen, continuing only single agent chemotherapy, or by introducing a new agent. Treatments that have been studied in randomized trials to date include chemotherapy, molecularly targeted agents, and immunotherapy approaches. After the development of multiple new agents that show activity in NSCLC and have a tolerable side effect profile, there has been increasing interest recently in this treatment strategy. In this study, we examine the evolution of this strategy by reviewing trials investigating the main treatment paradigms used in maintenance therapy for NSCLC. PMID- 20354451 TI - AT-101, a pan-Bcl-2 inhibitor, leads to radiosensitization of non-small cell lung cancer. AB - INTRODUCTION: Radiotherapy has a central role in the treatment of lung cancer. However, its effectiveness is often limited, in part, because of the defects in key apoptosis regulators, such as Bcl-2 family members, that contribute to cancer ability to evade apoptosis. In this study, we tested AT-101, a pan-Bcl-2 inhibitor, as a potential radiosensitizer in lung cancer. METHODS AND RESULTS: Clonogenic assays were used to determine the radiosensitivity of multiple lung cancer cell lines. On the basis of their relative response to radiotherapy, lung cancer cells were stratified into two groups, and a representative cell line of each group was selected for more in-depth study: A549 (resistant) and HCC2429 (sensitive). The expression levels of antiapoptotic (Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic (Bax, Bak, and Bid) Bcl-2 proteins were determined for each group. Although the levels of Bcl-2 and Mcl-1 were low for both groups, Bcl-XL expression was dramatically higher in A549, whereas almost not detected in HCC2429. The levels of Bax/Bak were 40% higher in HCC2429 compared with A549. When administered alone, AT-101 resulted in increased apoptosis in concentration dependent manner against both groups, with enhanced activity in HCC2429 even at lower concentration. Furthermore, AT-101 promoted radiosensitivity of A549 and HCC2429 cells (p < 0.005). Consistent with 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay findings, A549 cells required increased AT-101 dose to achieve a similar cytoxicity to HCC2429 cells. CONCLUSIONS: These investigations suggest that the Bcl-2 family may serve as effective therapeutic targets in lung cancer. Further clinical studies are warranted to assess the potential of AT-101 as an agent that enhances the therapeutic ratio of radiotherapy in lung cancer. PMID- 20354452 TI - Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. AB - BACKGROUND: Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas. PATIENTS AND METHODS: Patients (n = 76) were randomized to either 6 mg/m MMC on day 1 and 125 mg/m irinotecan on days 2 and 9 (arm A) or 3 mg/m MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick the-winner" approach based on efficacy. RESULTS: The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative. CONCLUSION: Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials. PMID- 20354453 TI - Randomized phase II trial of cisplatin, etoposide, and radiation followed by gemcitabine alone or by combined gemcitabine and docetaxel in stage III A/B unresectable non-small cell lung cancer. AB - PURPOSE: Southwest Oncology Group 9504 demonstrated the feasibility and potential benefit of docetaxel consolidation after etoposide, cisplatin, and radiotherapy in patients with locally advanced non-small cell lung cancer. Our study assessed consolidation with either gemcitabine alone or with docetaxel after identical chemoradiation as used in Southwest Oncology Group 9504. METHODS: Patients with stage III non-small cell lung cancer and good performance status were included. Treatment consisted of concurrent cisplatin 50 mg/m on days 1 and 8 plus etoposide 50 mg/m on days 1 to 5 for two 28-day cycles plus radiotherapy (62 Gy, 2 Gy daily in 31 fractions over 7 weeks), followed by randomization to either gemcitabine 1000 mg/m on days 1 and 8 (G) or gemcitabine 1000 mg/m on days 1 and 8 plus docetaxel 75 mg/m on day 1 (GD) every 21 days for three cycles. RESULTS: Eighty-three patients were entered, 81 received induction therapy, and 64 were randomized (32 in each arm). Grade 3 or four events, including neutropenia (56.3% vs. 28.1%, p = 0.03), anemia (18.8% vs. 3.1%, p = 0.05), and fatigue (15.6% vs. 6.3%, p = NS), were more frequent with GD compared with G. Among all patients, median survival from registration was 20.8 months (95% confidence interval: 16.4 33.8), and 2-year survival was 46.7% (95% confidence interval: 35.6-57.1). From randomization, median progression-free survival was 5.4 months for G and 13.4 months for GD, and median survival was 16.1 months for G and 29.5 months for GD. Two-year survival rates were 40.6% for G and 55.7% for GD. CONCLUSION: The doublet, as expected, resulted in more toxicity, particularly myelosuppression and fatigue. Survival associated with the GD treatment arm of this trial exceeds that of previously reported trials. PMID- 20354454 TI - CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. AB - INTRODUCTION: Metastasis-associated protein CD24 has been identified as a new prognostic factor and stem cell marker in the human neoplasm. However, the importance of the CD24 in non-small cell lung carcinomas (NSCLCs) has not been elucidated well. METHODS: We evaluated CD24 expression in 267 consecutive cases of NSCLC by immunohistochemistry using a tissue microarray technique and correlated with clinicopathologic parameters including forthcoming (seventh) new tumor node metastasis classification. RESULTS: CD24-high expression was demonstrated in 87 of 267 (33%) and was associated with adenocarcinoma (ADC) histology than in squamous cell carcinoma histology (64 of 165 [39%] vs. 20 of 88 [23%]; p = 0.023). Patients with CD24-high tumors tended to have a higher risk of disease progression (p < 0.001) and cancer-related death (p = 0.002). Multivariate analysis proved CD24-high expression as independent prognostic factors of disease progression and cancer-related death (p = 0.002, hazard ratio = 1.78, 95% confidence interval = 1.23-2.58 and p = 0.017, hazard ratio = 1.93, 95% confidence interval =1.13-3.31). CD24-high expression had a tendency to correlate with new pathologic stage (p-stage) (p = 0.089) rather than old p-stage (p = 0.253). Performance status and new p-stage, regardless of the tumor histology, were identified as consistent independent prognostic factors of disease progression and cancer-related death. However, age was related to a significantly shorter cancer-specific survival in ADC only. CONCLUSIONS: CD24 expression in NSCLC is associated with ADC histology and disease progression and cancer-related death, indicative of aggressive tumor behavior. Performance status and new p-stage, to a lesser extent, age correlated with progression-free survival and cancer-specific survival, regardless of tumor histology. PMID- 20354455 TI - MEK1 and AKT2 mutations in Japanese lung cancer. AB - BACKGROUND: Recently, to identify potential somatic mutations in genes of epidermal growth factor receptor (EGFR) signaling pathway, MEK1 gene mutation at exon 2 and mutation of the AKT2 (v-akt murine thymoma viral oncogene homologue 2) gene at kinase domain have been reported in non-small cell lung cancer. METHODS: We investigated the MEK1 mutation (n = 280) and AKT2 mutation (n = 273) in surgically treated non-small cell lung cancer cases. The presence or absence of MEK1 mutation (exon 2) and AKT2 mutation at kinase domain was analyzed by direct sequences. RESULTS: MEK1 mutation (K57K) was found from 1 of 280 patients with lung cancer (0.4%) and detected only one case (0.4%) of AKT2 mutation (R371H) in our cohort. MEK1 mutation was exclusive with EGFR, K-ras, and B-raf mutations at kinase domain. However, AKT2 mutation was coexisted with EGFR and PIK3CA mutations. CONCLUSION: This study demonstrated that mutation in the kinase domain of AKT2 and MEK1 exon 2 mutation occurred in a small fraction of Japanese lung cancers. PMID- 20354456 TI - Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. AB - BACKGROUND: Performance status (PS) is an important factor in determining survival outcome in non-small cell lung cancer (NSCLC) but is generally confounded by stage, age, gender, and smoking status. We investigated the prognostic significance of PS taking into account these important factors. METHODS: Retrospective analysis of registry database of the National Hospital Study Group for Lung Cancer (NHSGLC) between 1990 and 2005. Univariate analysis was performed using Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards model to identify independent prognostic factors. RESULTS: A total of 26,957 patients with NSCLC were analyzed of which 12,613 patients (46.8%) had World Health Organization (WHO) PS = 0, 8,137 patients were never smokers (30.2%), and most of them were females (72.7%). The majority of PS = 0 patients presented with stage I disease (56.9%). Patients with PS = 0 constituted the group with the highest proportion of never smokers (36.7%). There was a significant difference in the median overall survival (OS) between patients with PS = 0 and PS = 1 (51.5 months versus 15.4 months, respectively; p < 0.0001) and among patients with various PS within individual American Joint Committee on Cancer stage (all p values <0.0001). Never smokers had significantly improved median OS than ever smokers (30.0 months versus 19.0 months, respectively; p < 0.0001). Multivariate analysis demonstrated good PS, never smoker (versus ever smoker; hazard ratio = 0.935, 95% confidence interval: 0.884-0.990; p = 0.0205), early stage, female gender, squamous cell carcinoma histology, and treatment were all as independent favorable prognostic factors. CONCLUSIONS: PS and smoking status are independent prognostic factors for OS in NSCLC. PMID- 20354457 TI - The influence of sex on efficacy, adverse events, quality of life, and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group non small cell lung cancer chemotherapy trials. AB - BACKGROUND: Female sex is a favorable prognostic factor in lung cancer. In small cell lung cancer, women have been shown to experience greater toxicity from chemotherapy, but there are few studies of sex-related toxicity in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This retrospective analysis evaluated the effect of sex on efficacy, adverse events (AEs), dose intensity (DI), and quality of life (QoL) in three phase III NSCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group; BR.10 (adjuvant chemotherapy), BR.14, and BR.18 (first-line advanced disease). Only patients with National Cancer Institute of Canada Clinical Trials Group data were included, and patients in the BR.10 observation arm were excluded. RESULTS: Of 1,108 patients analyzed, 29% were female. On study entry, women were less likely to be overweight or obese (40% versus 51%, p < 0.0001), more likely to have adenocarcinoma (70% versus 44%, p < 0.0001), and less likely to be anemic at baseline (29% versus 55%, p < 0.0001) or have medical comorbidities. There were no significant differences in response rate to chemotherapy (27% versus 31%, p = 0.44 [excluding BR.10]), grade 3 or 4 AEs, DI, or QoL between sexes, although women reported more nausea and vomiting of any grade (77% versus 66%, p = 0.0004). In multivariate analysis, women had longer progression-free survival than men (hazard ratio 0.83, 95% confidence interval 0.71-0.97, p = 0.02) but not overall survival (hazard ratio 0.89, 95% confidence interval 0.75-1.05, p = 0.17). CONCLUSION: Women demonstrate modestly longer progression-free survival than men in chemotherapy-treated NSCLC, with no differences observed in response rates, serious AEs, or QoL. PMID- 20354458 TI - Endobronchial ultrasound-guided transbronchial needle aspiration for lymph node staging in patients with non-small cell lung cancer in non-operable patients pursuing radiotherapy as a primary treatment. AB - INTRODUCTION: Carbon ion radiotherapy (CIRT) is a promising modality with excellent localization and significant biologic effects on tumors. Nevertheless, success depends primarily on accurate staging before radiotherapy. Surgical interventions should be avoided in patients considered for CIRT because they usually have multiple comorbidities. The aim of this study was to evaluate the effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in patients with non-small cell lung cancer before CIRT. METHODS: From April 2005 to December 2007, 49 patients with non small cell lung cancer considered for CIRT with abnormal positron emission tomography-computed tomography (PET-CT) accumulations in the mediastinum and/or hilum were evaluated by EBUS-TBNA. The convex probe EBUS was used for EBUS-TBNA. RESULTS: There were 38 men and 11 women. Their mean age was 75.2 years (range: 55 87). Based on PET-CT, clinical staging was four with N1 disease, 42 with N2 disease, and three with N3 disease. By histology, 26 patients had adenocarcinoma, 19 had squamous cell carcinoma, and four had other histologies. All positive lymph nodes on PET-CT were aspirated (range: 1-5; average 2.55 lymph nodes/patient). EBUS-TBNA diagnosed 43 cases as N0 disease and as a result underwent CIRT. Forty of the 43 cases remained in stable condition without local recurrences (follow-up 6-46 months). The diagnostic accuracy of EBUS-TBNA for lymph node staging was 93.9%. CONCLUSIONS: EBUS-TBNA offers accurate minimally invasive lymph node staging in patients who are candidates for CIRT. EBUS-TBNA can be safely performed with a high diagnostic accuracy before CIRT. PMID- 20354459 TI - A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. AB - Allovectin-7, a bicistronic plasmid encoding human leukocyte antigen-B7 and beta 2 microglobulin formulated with a cationic lipid system, is an immunotherapeutic agent designed to express allogeneic major histocompatibility complex class I antigen upon intralesional administration. A phase 2 dose-escalation study (VCL 1005-208) was conducted to evaluate the safety and efficacy of Allovectin-7 in patients with metastatic melanoma. Eligible patients had stage III or IV metastatic melanoma recurrent or unresponsive to prior therapy, an Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients with brain or visceral (except lung) metastases, abnormal lactate dehydrogenase, or any lesion greater than 100 cm were excluded. Patients received six weekly intralesional injections followed by 3 weeks of observation and evaluation. Overall response was assessed using Response Evaluation Criteria in Solid Tumors guidelines. Patients with stable or responding disease were eligible to receive additional cycles of Allovectin-7. All 133 patients were evaluated for safety and 127 patients (2 mg, high dose) were evaluated for efficacy. Fifteen patients (11.8%, 95% confidence interval: 6.2-17.4) achieved an objective response with median duration of response of 13.8 months (95% confidence interval: 8.5, not estimable). A histological examination of tissue from two responding patients who had their lesions resected has shown no evidence of melanoma. Median time-to-progression in this study was 1.6 months. In conclusion, these results indicate that high-dose Allovectin-7 seems to be an active, well-tolerated treatment for selected stage III/IV metastatic melanoma patients with injectable cutaneous, subcutaneous, or nodal lesions. PMID- 20354460 TI - Song memory in female birds: neuronal activation suggests phonological coding. AB - Male Bengalese finches sing complex song sequences during courtship. To examine the female perception of sequence complexity, we tested female auditory processing with respect to sequential differences in the caudomedial nidopallium and caudomedial mesopallium. Repeated song presentations caused lower expression of the immediate early gene ZENK; however, consecutive presentation of a new song reinduced full ZENK expression. We presented a sequence-shuffled version of the father's song after repeated presentation of the original (unmodified) father's song. The shuffled songs caused lower ZENK expression in both the caudomedial nidopallium and caudomedial mesopallium. Although phonological differences caused full ZENK expression, sequential differences in song elements did not induce ZENK expression. Thus, it appears that female song perception is based on phonological, rather than sequential, information. PMID- 20354461 TI - Naturally fluctuating low incidence of invasive pneumococcal infections not affected by large-scale haemophilus influenzae type B vaccination. AB - BACKGROUND: Since many pathogens colonize the child's oro/nasopharynx in a similar manner, elimination of diseases such as those caused by Haemophilus influenzae type b (Hib) has a potential of augmenting other serious infections. Streptococcus pneumoniae is an agent of special interest now that Hib conjugates have been used widely for more than 2 decades. PATIENTS AND METHODS: All blood and cerebrospinal fluid isolations of Hib and S. pneumoniae were collected prospectively from 85,000 Finnish children at age 0-15 years by one central laboratory during 27 years. RESULTS: Hib vaccination, launched in 1986-1988, led to a quick decline of cases until the last was detected in 1991. In the next few years, the incidence of bacteremic S. pneumoniae infections increased, but now for 15 years, the numbers of cases have been slowly declining. This finding is not explained by less active sample-taking because the number of blood cultures have almost doubled in the past years. CONCLUSIONS: Large-scale Hib vaccination does not increase the incidence of pneumococcal diseases which continue their year-to-year fluctuation at low levels. Only a years-long follow-up permits conclusions on a vaccination's potential influence on the epidemiology of other diseases. PMID- 20354462 TI - Concomitant respiratory viral infections in children with Kawasaki disease. AB - The role of respiratory viruses in the pathogenesis of Kawasaki disease (KD) remains controversial. In this study, we showed that 8.8% of patients with KD had documented respiratory viral infections. Patients with concomitant viral infections had a higher frequency of coronary artery dilatations and were significantly more often diagnosed with incomplete KD. The presence of a concomitant viral infection should not exclude the diagnosis of KD. PMID- 20354463 TI - Incremental effectiveness of second dose varicella vaccination for outbreak control at an elementary school in Philadelphia, pennsylvania, 2006. AB - BACKGROUND: In 2006, the Philadelphia Department of Public Health conducted an investigation of a varicella outbreak at an elementary school in which second dose vaccination for outbreak control (VOC) was implemented. We evaluated the effectiveness of this intervention. METHODS: Self-administered questionnaires collected varicella disease and vaccination information. Students eligible for second-dose VOC were 1-dose vaccine recipients without prior varicella disease. A breakthrough varicella case was defined as a maculopapulovesicular rash in a student with onset >42 days after 1-dose vaccination without other apparent cause. Vaccine effectiveness was evaluated using survival analysis techniques and analyzed by vaccine status (first dose versus second dose). Multivariable Cox proportional hazard models were used to identify statistical interactions and adjust for confounders. RESULTS: The questionnaire response rate was 92% (342/370). Of the 286 eligible students, 187 (65%) received a second-dose VOC. The crude attack rate was 9/187 (5%) among second-dose VOC recipients; 43/99 (43%) among 1-dose recipients, and 5/6 (83%) among unvaccinated students. Second dose VOC recipients had milder rashes, compared with 1-dose or unvaccinated students. The adjusted incremental second-dose vaccine effectiveness was 76% (95% confidence interval: 44%-90%) for students with classroom exposure. Incremental effectiveness was similar (79%) when we extended the immune response time from 4 days to 7 days after second-dose VOC. CONCLUSIONS: Second-dose VOC resulted in a substantial reduction in varicella incidence for students with classroom exposure. Until high rates of routine second-dose vaccine coverage are achieved, clinicians should consider second-dose VOC an appropriate intervention to reduce disease transmission in institution-based outbreaks. PMID- 20354464 TI - Reduction in gastroenteritis in United States children and correlation with early rotavirus vaccine uptake from national medical claims databases. AB - BACKGROUND: We sought to estimate rotavirus disease reduction among children in hospital and office settings in the 4 US regions following rotavirus vaccine introduction and to estimate vaccine uptake. METHODS: Two national third-party payer medical claims databases were used to examine the number of visits for gastroenteritis per annual nongastroenteritis visits among children aged <5 years during July 2003 to June 2008 in hospital and office settings. The gastroenteritis burden attributable to rotavirus was computed as the excess of all gastroenteritis visits during rotavirus seasons above the baseline of visits during nonrotavirus periods. Rotavirus vaccine uptake was estimated by comparing claims for rotavirus vaccine with those for diphtheria-tetanus-acellular pertussis vaccines. RESULTS: In the South, Northeast, and Midwest, the typical winter-spring gastroenteritis peak due to rotavirus was markedly dampened in 2007 2008. Compared with the mean for 3 prevaccine seasons, the excess gastroenteritis visits that occurred during the 2007-2008 rotavirus season was reduced by >90% among infants in all care settings in 3 regions and by >70% among children aged 1 to 4 years. In the West, disease reductions were lower (53%-63% reduction among hospitalized infants). At the onset of the 2007-2008 season, coverage with > or =1 rotavirus vaccine dose was an estimated 57% among infants, 17% among children aged 1 year, and 0 among those aged 2 to 4 years. CONCLUSIONS: The rotavirus burden in 2007-2008 was markedly reduced in all US regions and exceeded that explained by only direct protection of the youngest vaccinated children. PMID- 20354465 TI - Bronchial microdialysis of cytokines in the epithelial lining fluid in experimental intestinal ischemia and reperfusion before onset of manifest lung injury. AB - Today, there is no continuous monitoring of the bronchial epithelial lining fluid. This study used microdialysis as a method of continuous monitoring of early lung cytokine response secondary to intestinal ischemia-reperfusion in pigs. The authors aimed to examine bronchial microdialysis for continuous monitoring of IL-1beta, TNF-alpha, IL-8, and fluorescein isothiocyanate Dextran 4,000 Da (FD-4). The superior mesenteric artery was cross-clamped for 120 min followed by 240 min of reperfusion (ischemia group, n = 8). Four sham-operated pigs served as controls. The pigs were anesthetized and normoventilated (peak inspiratory pressure, <20 cm H2O; positive end-expiratory pressure, 7 cm H2O). Samples from bronchial and luminal intestinal and arterial microdialysis catheters (flow-rate of 1 MUL/min) were collected during reperfusion in 60-min fractions. Samples were analyzed for TNF-alpha, IL-1beta, IL-8, and FD-4. Data are presented as median (interquartile range). A lung biopsy was collected at the end of the experiment. During reperfusion, there was an increase in bronchial concentrations of both IL-8 (3.70 [1.47-8.93] ng/mL per h vs. controls, 0.61 [0.47-0.91] ng/mL per h; P < 0.001) and IL-1beta (0.32 [0.05-0.56] ng/mL per h vs. controls, 0.07 [0.04-0.10] ng/mL per h; P = 0.008). In the intestinal lumen, IL-8 was increased in the ischemia group (6.33 [3.13-9.23] ng/mL per h vs. controls, 0.89 [0.21-1.86] ng/mL per h; P < 0.001). The FD-4 did not differ between groups. Pulmonary vascular resistance and pulmonary shunt increased versus controls. During reperfusion, PaO2/FiO2 ratio decreased in the ischemia group. Histology was normal in both groups. Bronchial microdialysis detects altered levels of cytokines in the epithelial lining fluid and can be used for continuous monitoring of the immediate local lung cytokine response secondary to intestinal ischemia-reperfusion. PMID- 20354466 TI - Effect of sagittal spinal balance, levels of posterior instrumentation, and length of follow-up on low back pain in patients undergoing posterior decompression and instrumented fusion for degenerative lumbar spine disease: a multifactorial analysis. AB - STUDY DESIGN: Prospective controlled clinical study on low back pain (LBP). OBJECTIVE: To investigate the possible effects of radiographic and other related parameters on LBP in patients underwent decompression and posterolateral instrumented fusion for degenerative lumbar spine disease. SUMMARY OF BACKGROUND DATA: Sagittal balance of the spine after spine surgery has gained increasing interest regarding its correlation with LBP and fusion rate. To our knowledge, no advanced statistical analysis on the effects of sagittal roentgenographic and other parameters on LBP after lumbar surgery has been published. METHODS: Forty five patients with an average age of 63 years, who underwent pedicle-screw fixation in 2, 3, and 4 vertebrae for degenerative lumbar spine disease were selected to be included in this study. Radiographic and self-assessment (bodily pain, short form-36) data were evaluated using advanced statistics (multifactorial analysis) to investigate all possible correlations between a dependent parameter (LBP) and independent parameters (sex, extension of instrumentation, sagittal spinal balance, and angular motion at the adjacent free level above instrumentation). RESULTS: All patients were observed for an average of 5.5 years (range, 5-7 years). Male patients showed significantly more improvement of LBP than female counterparts (P = 0.024). LBP improved after surgery by the first year (P < 0.000) and thereafter decreased (P < 0.000) at the final evaluation, but remained at levels significantly higher than before surgery (P < 0.000). The deviation of the apical lumbar vertebra from C7-plumbline was correlated with LBP (P < 0.000). Patients, who received third- and fourth- level instrumentation had less LBP (P = 0.0245) than their counterparts, who received second-level instrumentation. CONCLUSION: Improvement of sagittal deviation of apical lumbar vertebra, instrumentation of third or fourth vertebrae, male gender, and fusion success were correlated with postoperative improvement of LBP after posterior decompression and pedicle screw fixation for symptomatic degenerative lumbar spine disease.This research suggests that the methods directed at the improvement in sagittal spinal balance of the lumbar spine, careful selection of fusion levels, and improvement of fusion rate might be beneficial for decreasing LBP after surgery in degenerative lumbar spine disease. PMID- 20354467 TI - Engineered disc-like angle-ply structures for intervertebral disc replacement. AB - STUDY DESIGN: To develop a construction algorithm in which electrospun nanofibrous scaffolds are coupled with a biocompatible hydrogel to engineer a mesenchymal stem cell (MSC)-based disc replacement. OBJECTIVE: To engineer a disc like angle-ply structure (DAPS) that replicates the multiscale architecture of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Successful engineering of a replacement for the intervertebral disc requires replication of its mechanical function and anatomic form. Despite many attempts to engineer a replacement for ailing and degenerated discs, no prior study has replicated the multiscale hierarchical architecture of the native disc, and very few have assessed the mechanical function of formed neo-tissues. METHODS: A new algorithm for the construction of a disc analogue was developed, using agarose to form a central nucleus pulposus (NP) and oriented electrospun nanofibrous scaffolds to form the anulus fibrosus region (AF). Bovine MSCs were seeded into both regions and biochemical, histologic, and mechanical maturation were evaluated with in vitro culture. RESULTS: We show that mechanical testing in compression and torsion, loading methods commonly used to assess disc mechanics, reveal equilibrium and time-dependent behaviors that are qualitatively similar to native tissue, although lesser in magnitude. Further, we demonstrate that cells seeded into both AF and NP regions adopt distinct morphologies that mirror those seen in native tissue, and that, in the AF region, this ordered community of cells deposit matrix that is organized in an angle-ply configuration. Finally, constructs demonstrate functional development with long-term in vitro culture. CONCLUSION: These findings provide a new approach for disc tissue engineering that replicates multi-scale form and function of the intervertebral disc, providing a foundation from which to build a multi-scale, biologic, anatomically and hierarchically relevant composite disc analogue for eventual disc replacement. PMID- 20354468 TI - Early rehabilitation targeting cognition, behavior, and motor function after lumbar fusion: a randomized controlled trial. AB - STUDY DESIGN: Open label randomized controlled trial with 3-, 6-, 12-month, and 2 to 3-year follow-up. OBJECTIVE: To investigate the effectiveness of a psychomotor therapy focusing on cognition, behavior, and motor relearning compared with exercise therapy applied during the first 3 months after lumbar fusion. SUMMARY OF BACKGROUND DATA: Postoperative management after lumbar fusion commonly focuses on analgesic pain control and activities of daily living. After 3 months, exercise therapy is often implemented. No randomized controlled trial has investigated early rehabilitation techniques conducted during the first 3 months after surgery. METHODS: The study recruited 107 patients, aged 18 to 65 years, selected for lumbar fusion because of 12 months of symptomatic spinal stenosis, spondylosis, degenerative/isthmic spondylolisthesis, or degenerative disc disease. The exercise therapy group received a home program focusing on pain contingent training of back, abdominal, and leg muscle functional strength and endurance, stretching, and cardiovascular fitness. The psychomotor therapy group received a home program and 3 outpatient sessions focusing on modifying maladaptive pain cognitions, behaviors, and motor control.Rated questionnaires investigating functional disability, pain, health-related quality of life, functional self-efficacy, outcome expectancy, fear of movement/(re)injury, and coping were assessed at 3, 6, 12 months, and 2 to 3 years after surgery. RESULTS: Follow-up rates were 93% at 12 months and 81% at 2 to 3 years after surgery. Psychomotor therapy improved functional disability, self-efficacy, outcome expectancy, and fear of movement/(re)injury significantly more than exercise therapy at respective follow-up occasions. Similar results occurred for pain coping but group differences were nonsignificant at 2 to 3 years follow-up. Potentially clinical relevant higher reoperation rates occurred after psychomotor therapy but rates were within normal ranges. CONCLUSION: The study shows that postoperative rehabilitation can be safely implemented during the first 3 months after lumbar fusion and should include measures to modify psychological as well as motor functions. PMID- 20354469 TI - Radiographic analysis of newly developed degenerative spondylolisthesis in a mean twelve-year prospective study. AB - STUDY DESIGN: Prospective study of community-based female volunteers. OBJECTIVE: To investigate the incidence of newly developed degenerative spondylolisthesis (DS) among those without baseline deformity, and to clarify radiographic characteristics and predictors of DS. SUMMARY OF BACKGROUND DATA: There has been limited number of prospective studies of DS. Our on-going cohort study of healthy volunteers enabled long-term observation of highly susceptible perimenopause female subjects. METHODS: A final total of 142 female subjects without spondylolisthesis at baseline radiographs were included and followed up for more than 8 years. Standardized serial entire spine radiographs were used to measure spinopelvic alignment, including pelvic incidence (PI), vertebral inclination angle, disc height, vertebral size, and facet orientation. RESULTS: The incidence of newly developed DS was 12.7%. Comparison between DS and non-DS subjects demonstrated that DS subjects had significantly greater baseline lumbar lordosis, PI, vertebral inclination angle, and smaller vertebral size. Exaggerated lumbopelvic alignment was more prominent in L3-DS than in L4-DS, and L4-DS was associated with the decrease in L4/5 disc height. Multivariate analysis revealed that PI, L4 vertebral inclination, adjusted vertebral size, and facet sagittalization were independent predictors of the development of DS. CONCLUSION: This was the first study to confirm the relationship of PI and the development of DS in a long-term prospective observation. Proposed pathogenetic differences might explain the fact that L4-DS is far more prevalent than L3-DS. The development of DS could be predicted by baseline lumbopelvic morphology among the highly susceptible perimenopause women. PMID- 20354470 TI - Quantitative dynamic measures of physical exposure predict low back functional impairment. AB - STUDY DESIGN: Prospective field study of work exposure and changes in back function. OBJECTIVE: Quantify dynamic physical exposures in the workplace and their association with decreases in kinematic back function (indicative of low back pain [LBP]). SUMMARY OF BACKGROUND DATA: Previous epidemiologic studies of work have measured gross categories of exposure and found moderate relationships with LBP. More precise quantitative measures of exposure and spine function were hypothesized to increase the chances of identifying any significant associations. METHODS: Three hundred and ninety real-time physical exposure measures were collected from distribution center workers performing repetitive manual materials handling tasks. Low back health effect measures were quantitatively measured prospectively for workers performing each of the jobs using a kinematic measure of function. RESULTS: Significant decreases in spine function were observed in workers associated with 40% of the jobs sampled. Numerous significant univariate odds ratios were identified that indicated an association between physical exposure and decreased function. A multivariate model including right lateral trunk velocity, timing of the maximum dynamic asymmetric load moment exposure, and the magnitude of the dynamic sagittal bending moment predicted reduced spine function well. The model resulted in excellent sensitivity (85%) and specificity (87.5%) as well as excellent positive predictive value (89.5%) and negative predictive value (82.4%). CONCLUSION: This study suggests that with proper quantification of job exposure and spine function, it is possible to identify which dynamic physical exposures are associated with reduced spine function and increases in LBP. PMID- 20354471 TI - In vivo measurement of lumbar facet joint area in asymptomatic and chronic low back pain subjects. AB - STUDY DESIGN: In vivo measurement of lumbar facet joint surface area. OBJECTIVE: To investigate lumbar facet joint surface area in relation to age and the presence of chronic low back pain. SUMMARY OF BACKGROUND DATA: Facet joint surface area is an important parameter for understanding facet joint function and pathology, but information on the lumbar facet joint is limited, especially in relation with age and low back pain symptoms. METHODS: In vivo measurements of the lumbar facet joints (L3/L4-L5/S1) were performed on 90 volunteers (57 asymptomatic subjects and 33 chronic low back pain subjects) using subject-based 3-dimensional facet joint surface computed tomography models. RESULTS: The facet joint surface area increased significantly at each successive inferior level. In the low back pain subjects aged >40 years, both superior and inferior facet surface areas increased except superior facets at L5/S1 compared with younger subjects. In the asymptomatic subjects aged >40 years, only the superior facets showed an increase in the L3/4 facet surface area compared with younger subjects. CONCLUSION: The lumbar facet areas measured in vivo in this study were similar to previous cadaveric studies. The lumbar facet area was significantly greater at the inferior lumbar levels and also increased with age. This age-related increase in the facet joint surface was observed more in the low back pain subjects compared with asymptomatic subjects. The increase in the area of the facet joint surface is probably secondary to increased load-bearing in the lower lumbar segments and facet joint osteoarthritis. PMID- 20354472 TI - Analysis of segmental cervical spine vertebral motion after prodisc-C cervical disc replacement. AB - STUDY DESIGN: Retrospective study of patients enrolled in a prospective randomized Food and Drug Administration trial with single level cervical disc replacement (CDR) with the ProDisc-C (Synthes, Paoli, PA). OBJECTIVE: Evaluate the segmental range of motion (ROM) in the cervical spine pre- and postoperative after CDR. SUMMARY OF BACKGROUND INFORMATION: Each cervical level is believed to have its own biomechanical characteristics, ultimately leading to different sagittal and lateral ROM. Our understanding of the factors that influence motion after CDR continues to change and expand. METHODS: One hundred sixty-four patients with single level ProDisc-C arthroplasty were evaluated radiographically using Medical Metrics (QMATM, Medical Metrics, Inc., Houston, TX). Pre- and postoperative disc height and ROM were measured from standing lateral and flexion extension radiographs. Of these 164 patients, 44 had a CDR at C6/C7, 96 at C5/C6, 18 at C4/C5, and 6 at C3/C4. The mean follow-up was of 24 months. Statistical analysis evaluated the difference in mean ROM between the groups. RESULTS: Before surgery, C4/C5 had more sagittal ROM compared with C3/C4, C5/C6, and C6/C7 (P < 0.001.) Before surgery, C4/C5 also had more lateral ROM compared with C3/C4, C5/C6, and C6/C7 (P = 0.015). After surgery, there were no significant differences in sagittal and lateral ROM between C3/C4, C4/C5, C5/C6, and C6/C7. The delta (difference between pre- and postoperative) proved that the C4/C5 CDR actually lost sagittal ROM (-2.5 degrees ) compared with the other levels, which gained sagittal ROM, C3/C4 (0.9 degrees ), C5/C6 (1.8 degrees ), and C6/C7 (1.6 degrees ); P = 0.037. There was no significant difference in the delta lateral ROM between the segments: C3/C4, C4/C5, C5/C6, and C6/C7. CONCLUSION: CDR approximates the different segmental sagittal and lateral ROM. Although C4/C5 had negative delta ROM in the sagittal and lateral planes, it provided a satisfactory final ROM. Long-term clinical outcome studies are needed to properly evaluate if these differences could ultimately affect the patients everyday life. PMID- 20354474 TI - Myelopathy hand: new evidence of the classical sign. AB - STUDY DESIGN: Motion analysis on video files that captured grip and release cycles with fingers. OBJECTIVE: To reveal the kinematic characteristics of finger motion in cervical myelopathy. SUMMARY OF BACKGROUND DATA: Myelopathy patients are often unable to smoothly move their fingers in grip and release cycles. Although paradoxical wrist motion (trick motion) and lack of finger coordination are well-known phenomena in myelopathy patients, it is not known which types of myelopathy patients present with these kinematic characteristics, and it is not known why they occur. METHODS: Thirty patients with myelopathy were evaluated before and after decompressive surgery and compared with 42 healthy controls. The subjects were asked to grip and release with their fingers as rapidly as possible for 15 seconds. Movies taken with a digital camera were divided into 3 animation files of 5-seconds each. Three physicians independently counted the number of finger grip and release cycles of those files in a blinded manner; they also evaluated trick motion of the wrist and lack of finger coordination. RESULTS: Both the frequency of trick motion and that of uncoordinated finger motion were significantly higher in the preoperative myelopathy group than in the control group (trick motion, 11.7% vs. 4.8% and uncoordinated finger motion, 15.6% vs. 7.1%), but were the same in the pre- and postoperative myelopathy groups. In the preoperative myelopathy group, the number of grip and release cycles of uncoordinated finger motion files, especially ulnar delay type, was significantly smaller than that of coordinated finger motion files, which meant uncoordinated finger motion was related to the severity of myelopathy. CONCLUSION: Both uncoordinated finger motion and trick motion of the wrist were more frequent in myelopathy patients than in healthy controls, and uncoordinated finger motion was associated with severity of myelopathy, whereas trick motion was not associated with either severity of myelopathy or level of cord compression. These findings contradict the conventional idea that trick motion is associated with the severity of myelopathy. PMID- 20354473 TI - The relationship between magnetic resonance imaging and quantitative electromyography findings in patients with compressive cervical myelopathy. AB - STUDY DESIGN: A retrospective comparison of magnetic resonance imaging (MRI) and quantitative electromyography (EMG) findings in patients with compressive cervical myelopathy (CCM). OBJECTIVES: To investigate which parameters of the EMG motor unit potentials (MUPs) as determined by automatic analysis of 4 muscles in the upper limb are correlated with spinal cord compression observed on MRI in CCM patients and to determine whether electrical and radiologic levels are correlated. SUMMARY OF BACKGROUND DATA: Increased mean duration of MUPs has been reported to be a sensitive indicator of disorders of the spinal motor neurons that are accompanied by axonal degeneration and regeneration. METHODS: MRI findings at each cervical disc level from C3/C4 to C6/C7 and MUPs recorded from 4 muscles (deltoid, biceps brachii, triceps brachii, and abductor digiti minimi) were examined to determine whether there is a statistical correlation between spinal cord compression and abnormal parameters of the MUPs for any combination of disc level and muscle. RESULTS: Significant correlations between increased mean duration of MUPs and radiologic level of cord compression were observed for deltoid and cord compression at C3/C4 (P < 0.01), biceps brachii and cord compression at C3/C4 (P < 0.001) and C4/C5 (P < 0.01), triceps brachii and cord compression at C5/C6 (P < 0.05), and abductor digiti minimi and cord compression at C6/C7 (P < 0.001). Other parameters of MUPs including amplitude, polyphasia and denervation potentials did not show significant correlation with compressive spinal cord lesions on MRI. CONCLUSION: Quantitative analysis of mean duration of MUPs provides a reliable indicator of physiologic disorder of spinal motor neurons in CCM and may contribute to establishing the site of motor neuron compromise in cases with multilevel spinal canal stenosis. PMID- 20354475 TI - Posterior transdiscal three-column shortening in the surgical treatment of vertebral discitis/osteomyelitis with collapse. AB - STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To evaluate the early surgical results and complications of thoracic transdiscal osteotomies and vertebral shortening for the treatment of thoracic discitis/osteomyelitis. SUMMARY OF BACKGROUND DATA: Thoracic discitis/osteomyelitis leads to collapse of the disc space and/or vertebral body. We propose a novel technique to achieve the same goals as anterior column reconstruction through an entirely posterior approach. Shortening of the vertebral column provides structural support without the morbidity of an anterior approach. METHODS: Following REB approval, retrospective review of the charts of five patients that underwent posterior only thoracic transdiscal osteotomies and vertebral shortening for discitis/osteomyelitis was carried out. Posterior only surgery was performed in these patients with excision of the affected disc space and corresponding posterior elements. Instrumented fusion was performed across the segment spanning multiple vertebral levels. Clinical outcome, radiographic correction, and perioperative complications were analyzed. RESULTS: Three patients had bacterial discitis, and 2 had tuberculosis. Mean age at the time of surgery was 61 years (50-76). Mean follow-up was 45 months (25-63). There was no neurologic deterioration; 2 patients with Frankel grade B improved to grade D and E, respectively. Mean kyphosis corrected from 36 degrees (14-90) to 4 degrees (0 8), and the mean construct spanned 9 levels (6-15). No major complications were encountered during surgery. Two patients underwent revision surgeries, 1 patient died of unrelated causes at 6 months. All patients were treated with a full course of postoperative antibiotic treatment. No cases of recurrent infection were recorded. CONCLUSION: Thoracic transdiscal osteotomy with vertebral shortening is a safe and effective option for the treatment of infectious discitis/osteomyelitis with associated kyphosis. With adjuvant antibiotics, it effectively eradicates the infection through a posterior only approach, avoiding the need for anterior procedures and long anterior struts. PMID- 20354476 TI - Direct evidence for sensory innervation of the dorsal portion of the Co5/6 coccygeal intervertebral disc in rats. AB - STUDY DESIGN: We examined the sensory innervation of the coccygeal (Co) 5/6 intervertebral disc in rats using a retrograde neurotracing method and immunohistochemistry. OBJECTIVE: To investigate the properties of the sensory innervation of the rat coccygeal disc. SUMMARY OF BACKGROUND DATA: Developing a rat disease model for degenerative intervertebral disc compression using lumbar discs is technically impractical because of their location. Coccygeal intervertebral discs are more readily accessible and several reports of morphologic evaluation of degenerative coccygeal intervertebral discs using compression devices exist. However, their sensory innervation and properties have not yet been characterized. METHODS: FluoroGold neurotracer was applied to the Co5/6 intervertebral discs of intraperitoneally anesthetized Sprague Dawley rats (n = 10). Subsequently, the discs and the L1-S4 dorsal root ganglions (DRGs) were resected and sectioned. The discs were double-stained for immunoreactivity to the neuronal marker beta-tubulin (Tuj-1) and biotin-labeled isolectinB4 (IB4), a neuropathic pain marker, or Tuj-1 and calcitonin gene-related peptide (CGRP), an inflammatory pain marker. The DRGs were double-stained for IB4-binding and CGRP immunoreactivity (IR). The proportions of IB4-binding or CGRP-IR DRG neurons were assessed by cell counting and compared. RESULTS: The disc immunohistochemistry showed evidence of sensory nerve fibers lying in the outermost layer of the anulus fibrosus. FluoroGold labeled DRG neurons mainly derived from S1 to S3 DRGs, especially S2 and S3. No labeled neurons were observed in the S4 DRG. The histochemistry of the DRGs showed a predominance of CGRP-IR DRG neurons (3.5 +/- 1.7% IB4-binding and 15.4 +/- 5.6% CGRP-IR on average). CONCLUSION: This study showed evidence for nerve fibers in the discs and predominant innervation by CGRP IR DRG neurons. The neurons innervating the discs mostly derived from S1 to S3 DRGs, especially S2 and S3. These findings may be useful in developing rat models of disease involving degenerative intervertebral disc compression. PMID- 20354477 TI - Contributory factors to postoperative spinal fusion complications for children with myelomeningocele. AB - STUDY DESIGN: This is a retrospective review of all children with myelomeningocele (MMC) who were undergoing surgery for scoliosis at our institution. OBJECTIVE: Our aim was to investigate possible correlations between poor nutritional indexes and/or positive urinary cultures before surgery to perioperative infection risk. SUMMARY OF BACKGROUND DATA: Patients who have scoliosis secondary to MMC have been shown to have a high rate of infectious complications. Many children with MMC have been found to have asymptomatic urinary tact infections due to their neurogenic bladder. There is little literature on risk factors for and ways to prevent postoperative infections for these patients. METHODS: We reviewed a comprehensive database for the outcome for spinal fusion surgeries of 59 patients with MMC treated at our institution over the past 45 years. Perioperative infections were correlated to preoperative nutritional status (measured by patient hematocrit [Hct]) and presence of active infection using Fisher Exact Probability Test. RESULTS: A total of 84 different spinal fusion operations for 59 patients were recorded. Patients presenting with poor preoperative nutrition (Hct50.0 mm neither for primary patency (P=0.94), nor for limb salvage (P=0.32). CONCLUSION: The cryoplasty technique is effective for the treatment of infrapopliteal lesions in CLI patients. The results seem to be within the range of those of conventional PTA. Especially for shorter lesion (<50.0 mm), the wide spread use of cryoplasty is not recommended. For lesions with a minimal length of 50.0 mm, the results are encouraging. PMID- 20354490 TI - Drug eluting stents versus PTA with GP IIb/IIIa blockade below the knee in patients with current ulcers--The BELOW Study. AB - The study was designed as a feasibility trial to evaluate the use of GP IIb/IIIa blockade in connection with drug eluting stents, bare stents and PTA only. Sixty patients with current ulcers were randomly assigned to receive abciximab plus a sirolimus coated stent (N.=14), abciximab plus a bare stent (N.=16), abciximab plus PTA (N.=14) and PTA alone (N.=19). Angiographic control was performed at two and six months. Recanalization was successful in all cases. Two month restenosis rate was 9%, 45.5%, 67% and 46%. At six month follow-up restenosis rate was 9%, 67%, 75% and 58%, respectively; 14% of all patients had major amputations within six months. Adjunctive administration of abciximab during peripheral arterial intervention below the knee was found to be safe. Sirolimus coated stent administration was followed by a higher patency rate. PMID- 20354491 TI - Developments in subintimal angioplasty in the infrainguinal segment. AB - Since it was first described in 1990, subintimal angioplasty (SIA) has become an established percutaneous procedure for the treatment of symptomatic lower limb arterial occlusions. The concept of this technique is to create a dissection in the subintimal plane in order to cross an occluded intraluminal segment, then to re-enter the true lumen of the patent distal artery. Balloon dilatation of this subintimal channel results in a new extraluminal lumen that is free of atheromatous plaque. It is a safe and effective procedure with advantages over intraluminal angioplasty and open surgery, thereby increasing the scope of endovascular therapy to include complex infrapopliteal occlusions and high-risk patients with limb-threatening ischaemia who are unsuitable for surgical revascularization. It has good primary success rates, long-term outcomes and does not compromise future surgical revascularization, resulting in a paradigm shift in the management of lower limb ischemia with many centres adopting SIA as first line therapy. This article aims to review the indications of SIA, variations and developments in the technique, outcomes and factors affecting patency, and complications associated with the procedure. PMID- 20354492 TI - Ischemic foot: definition, etiology and angiosome concept. AB - Ischemic foot is a condition of decreased arterial perfusion. It has several etiologies, atherosclerotic peripheral arterial disease, including that secondary to diabetes mellitus, being the most common. Other potential causes of ischemic foot are acute embolism from cardiac, arterial or paradoxical sources, and thrombosis secondary to arterial blood clots due to procoagulative states (e.g. vasculitis and hematologic disorders), arterial spasms or injury resulting from drug use or from external or iatrogenic trauma. Prompt diagnosis and revascularization of the affected limb play a crucial role in the treatment of ischemic foot. The angiosome principle, defined by Ian Taylor's landmark anatomic study in 1987, divides the body into three-dimensional anatomic units of tissue fed by a source artery (the angiosome). Detailed knowledge of the vascular anatomy of the leg, and in particular of angiosomes in the foot, helps the clinician make better decisions when dealing with ischemic foot. The physician can better estimate the possibility of wound healing, and decide which type of revascularization has the most chance of success, given the existing blood supply. If surgical or endovascular revascularization is successful, the foot should no longer appear ischemic and painful, and the wounds should granulate. Newly granulating wounds should be carefully protected, and meticulous daily local wound care should be performed to promote healing and prevent infection. The quality of subsequent wound care is also a critical component in promoting healing and avoiding further tissue loss. PMID- 20354493 TI - Update on the TURBO BOOSTER spectranetics laser for lower extremity occlusive disease. AB - In the last two decades the endovascular treatment of peripheral arterial occlusive disease (PAOD) has gained a widespread and predominant role. New technologies have developed in the last years as atherectomy devices, self expandible nitinol stents, drug eluting devices (stent and balloons), absorbable stents. In recent years, growing interest has been dedicated to laser technology due to device improvements and literature data reporting safety and efficacy of excimer laser. The role of this new endovascular technique for the treatment of atherosclerotic arterial diseases should be considered with regard to two fields of interest: the claudicatio intermittens (CI) and the critical limb ischemia (CLI). A 20-year history with medical lasers has proven that not all lasers are equal. Lasers used and studied in the late 1980s and 1990s had poor outcomes due to inappropriate laser selection and undefined laser techniques. Over the last 10 years, multicenter studies with the excimer laser confirm that case selection, appropriate utilization of equipment, application of safe lasing techniques, and knowledge of indications and contraindications, all contribute to the successful application of laser-assisted angioplasty in complex coronary and peripheral artery disease. If applied properly, the Excimer Laser is a useful technique to transform complex obstructive arterial disease into more treatable lesions, improving the results of endovascular treatment and lowering the threshold of intervention for ''untreatable'' patients. New larger studies are requested to assess the definitive role of this technique in PAD treatment and limb salvage. This review will discuss the Laser Phisics and application in PAD along with the clinical data available to support the Excimer Laser as a reliable technology for endovascular intervention. PMID- 20354494 TI - Association of plaque echostructure and cardiovascular risk factors with symptomatic carotid artery disease. AB - AIM: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. METHODS: Cross sectional study of consecutive patients with significant (>50%) ICA stenosis. Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (>50%) ICA stenosis. RESULTS: The asymptomatic and symptomatic groups did not differ in terms of gender distribution (P=0.76) and severity of stenosis (P=0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (P=0.004, OR=2.13, 95% CI=1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (P=0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. CONCLUSION: Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation. PMID- 20354495 TI - Validation of the Simulator for Testing and Rating Endovascular SkillS (STRESS) machine in a setting of competence testing. AB - AIM: Endovascular skills are an integral part of modern-day vascular surgery. The STRESS machine has been developed to test these skills in vascular surgeons. This study aims to define an optimal pass/fail cutoff value for the STRESS test score. METHODS: The STRESS machine consists of a dry glass model of the abdominal aorta and its tributaries with various stenotic lesions, elongations, and tortuosities. A camera and computer software are used to simulate plain fluoroscopy-mode. The test subjects are given two assignments after which two reviewers use a combination of the ICEPS and MRS to produce the final total score; 43 subjects were tested. According to previous endovascular experience, subjects were classified into four groups: novice-low (no experience, less than 11 performed procedures, less than 50 assisted procedures), novice-high (11-25 performed procedures, more than 50 assisted procedures), intermediate (1-10 performed and >11-25 assisted procedures, 11-25 performed and >1-10 assisted procedures or 25 50 performed procedures) and advanced (more than 50 performed procedures). RESULTS: Test-score and noted experience showed a correlation of 0.794. All intermediate and advanced test subjects scored more than 50 points compared to 4 out of 15 novices. CONCLUSION: We demonstrated that it is possible to determine an optimal cut-off value for competence testing with the STRESS machine. PMID- 20354496 TI - Application of low-volume zero-balanced ultrafiltration and its effect on blood propofol concentration: a randomized controlled trial. AB - AIM: The aim of this study was to evaluate the effectiveness of low-volume zero balanced ultrafiltration during cardiopulmonary bypass in heart valve replacement surgery. METHODS: This was a randomized, double-blind, controlled study carried out in the operating room. Forty patients of ASA grade II-III, elected to undergo heart valve replacement surgery, were enrolled. All patients were randomly assigned to either a low-volume (35 mL/kg) zero-balanced ultrafiltration group (N.=20) or to a control group (N.=20). Blood propofol concentrations and entropy index were measured using cardiopulmonary bypass. Concentrations of plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and cardiac troponin I were measured before and after the end of cardiopulmonary bypass and corrected according to hematocrit. RESULTS: Blood levels of cardiac troponin I, TNF-alpha, IL-6, and IL-10 after surgery were all significantly lower in the ultrafiltration group than in the control group (P<0.05) after the end of bypass. Blood propofol concentrations decreased significantly in both groups during cardiopulmonary bypass and remained significantly lower in the ultrafiltration group than the control group. However, there was no significant difference between the two groups in the entropy index (P=0.5583). CONCLUSION: Low-volume zero-balanced ultrafiltration performed during cardiopulmonary bypass surgery significantly decreased post-bypass levels of the cytokines, TNF-alpha, IL-6, IL-10, and postoperative cardiac troponin I. Blood propofol concentration was also decreased; however, the depth of anesthesia was not affected significantly. PMID- 20354497 TI - Clinical relevance of eNOS T-786C polymorphism for hospital mortality and morbidity in cardiac surgical patients. AB - AIM: The endothelial nitric oxide (eNOS) gene T-786C polymorphism may influence as a genetic risk factor cardiovascular diseases and shows association with cardiovascular mortality. We hypothesized that this polymorphism may lead to increase mortality and morbidity after cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In 500 patients who underwent cardiac surgery with CPB we investigated the eNOS T-786C polymorphism by DNA-sequencing. The patients were grouped according to their genotype in three groups (TT, TC, and CC). RESULTS: The overall genotype distribution of T-786C polymorphism was TT=41.6%, TC=51.2%, and CC=7.2% respectively. The groups did not differ in age and gender. No significance was shown in preoperative risk factors, excluding peripheral disease (P=0.03). No difference was shown in Euroscore, APACHE II, and SAPS II. The usage of norepinephrine (P=0.03) and nitroglycerine (P=0.01) was significant higher in TC allele carrier. The mortality was quite uniform across elective and urgent subgroup. However, we found a significant difference concerning mortality and emergency cardiac procedures in homozygous C-allele carrier (P=0.014). CONCLUSION: The present study demonstrates that this polymorphism contributes to a higher prevalence of postoperative mortality after emergency cardiac surgery. Thus, the eNOS T-786C polymorphism could serve as a possibility to differentiate high risk subgroups in heterogeneous population of individuals with cardiac diseases who need cardiac surgery with CPB. PMID- 20354498 TI - Deep pericardial sling versus lateral pericardial sutures in off-pump coronary artery bypass surgery. AB - AIM: The aim of this study was to evaluate the safety and efficacy of deep pericardial sling (DPS) versus lateral pericardial sutures (LPSs) for heart stabilization and adequate coronary artery exposure during off-pump coronary artery bypass surgery (OPCAB). METHODS: One surgeon employed in 101 consecutive patients a series of four to six 2-0 polyglactin sutures placed laterally between the left phrenic nerve and the left pulmonary veins (LPS). Two other surgeons used in 104 consecutive patients a single 0-0 braided silk suture with moistened gauze placed in the oblique sinus of the posterior pericardium, between the inferior vena cava and the right lower pulmonary vein (DPS). RESULTS: One conversion to beating heart surgery with cardiopulmonary bypass support occurred in each study group. No patient in the LPS group was converted to DPS technique. The use of LPSs allowed a number of distal anastomoses somewhat higher than the DPS technique (4.1+/-1.1 vs. 3.7+/-1.1, P=0.02). Postoperative results were similar in both study groups. A lower incidence of postoperative low-cardiac output syndrome and of prolonged need of inotropes has been observed in the LPS group, but the difference failed to reach statistical significance. One patient in the LPS group had postoperative left phrenic nerve palsy. One patient in the DPS group suffered of intraoperative bleeding secondary to rupture of the inferior vena cava likely related to placement of DPS, which was successfully repaired. CONCLUSION: LPS technique is as effective as DPS technique and allows complete revascularization with a postoperative outcome similar to the latter technique. PMID- 20354499 TI - The effects of load on systolic mitral annulus movements by tissue Doppler imaging in cardiac surgery patients. AB - AIM: The main indexes of ventricular function used in clinical practice are strongly influenced by the ventricular load conditions. Tissue Doppler imaging (TDI) has been reported to be a powerful modality that enables assessment of ventricular wall motion with a high temporal and spatial resolution. The study of the systolic movements of the mitral annulus has been proposed as a valid index of myocardial contractility. The aim of this study was to verify if the systolic movements of the mitral annulus by TDI are load-dependent in patients undergoing coronary artery bypass grafting. We evaluated the effect of load changes on systolic (S(M)) and isovolumic (S(IVC)) velocity waves, and on isovolumic acceleration (S(IVA)). METHODS: Twenty-three patients undergoing coronary artery bypass grafting were evaluate. Load was changed with a rapid infusion of 7 cc/kg of a gelatin solution. The sample volume of TDI was placed at the lateral side of the mitral annulus in the mid-esophageal 4-chamber view. RESULTS: The increase preload resulted in a statistically significant increase of S(M) (8.7+/-1.04 cm/s vs. 9.99+/-0.88 cm/s P=0.01), and a statistically significant increase of S(IVC) (5.65+/-1.95 cm/s vs. 6.75+/-1.53 cm/s P=0.03). S(IVA) does not appear to be changed after the increase of preload (203.45+/-45.69 cm/s(2) vs. 211.41+/-71.28 p=0.81). CONCLUSION: Only S(IVA) seems to be an independent index of cardiac functionality in cardiac surgery patients and appears to be an optimum index in the clinical evaluation of these patients. PMID- 20354500 TI - L-arginine supplemented nondiluted blood cardioplegia: a clinical trial. AB - AIM: L-arginine was shown to improve protection of the myocardium during coronary artery bypass graft (CABG) surgery. The objective of the present study was to determine the concentration of L-arginine to obtain the most effective protection of the myocardium during CABG surgery. METHODS: Seventy-five patients undergoing CABG surgery were randomized in 3 groups. The first group (N.=25) was administered a placebo injection in the blood cardioplegic solution, the second group (N.=25) received an injection of 4 mmol/L of L-arginine and a third group (N.=25) an injection of 6 mmol/L of L-arginine in the blood cardioplegic solution. Blood samples from the ascending aorta and the coronary sinus catheter were collected before, immediately after and at 20 minutes after aortic cross clamping. Total plasmatic nitrite and nitrate ratio and lactate release from the myocardium in the collected blood samples were measured. RESULTS: Seventy-five patients averaging 62+/-7 years of age and undergoing 3.1+/-1 coronary bypass grafts during 41+/-17 minutes of aortic cross clamping time were recruited. Values of total plasmatic nitrite and nitrate ratio remains non-significant before and after aortic clamping and also between groups (P=0.9812 and 0.3573 respectively). Myocardial lactate release was statistically different before and after cross clamping (P=0.0002) and also between the 3 groups (P=0.0311). CONCLUSION: Nondiluted blood cardioplegic solution supplemented with 4 mmol/L of L-arginine was associated with a significant decrease of myocardial lactate release after aortic cross-clamping and reperfusion during CABG surgery. PMID- 20354502 TI - Identification of growth inhibition phenotypes induced by expression of bacterial type III effectors in yeast. AB - Many Gram-negative pathogenic bacteria use a type III secretion system to translocate a suite of effector proteins into the cytosol of host cells. Within the cell, type III effectors subvert host cellular processes to suppress immune responses and promote pathogen growth. Numerous type III effectors of plant and animal bacterial pathogens have been identified to date, yet only a few of them are well characterized. Understanding the functions of these effectors has been undermined by a combination of functional redundancy in the effector repertoire of a given bacterial strain, the subtle effects that they may exert to increase virulence, roles that are possibly specific to certain infection stages, and difficulties in genetically manipulating certain pathogens. Expression of type III effectors in the budding yeast Saccharomyces cerevisiae may allow circumventing these limitations and aid to the functional characterization of effector proteins. Because type III effectors often target cellular processes that are conserved between yeast and other eukaryotes, their expression in yeast may result in growth inhibition phenotypes that can be exploited to elucidate effector functions and targets. Additional advantages to using yeast for functional studies of bacterial effectors include their genetic tractability, information on predicted functions of the vast majority of their ORFs, and availability of numerous tools and resources for both genome-wide and small-scale experiments. Here we discuss critical factors for designing a yeast system for the expression of bacterial type III effector proteins. These include an appropriate promoter for driving expression of the effector gene(s) of interest, the copy number of the effector gene, the epitope tag used to verify protein expression, and the yeast strain. We present procedures to induce expression of effectors in yeast and to verify their expression by immunoblotting. In addition, we describe a spotting assay on agar plates for the identification of effector induced growth inhibition phenotypes. The use of this protocol may be extended to the study of pathogenicity factors delivered into the host cell by any pathogen and translocation mechanism. PMID- 20354503 TI - The Arabidopsis P450 protein CYP82C2 modulates jasmonate-induced root growth inhibition, defense gene expression and indole glucosinolate biosynthesis. AB - Jasmonic acid (JA) is a fatty acid-derived signaling molecule that regulates a broad range of plant defense responses against herbivores and some microbial pathogens. Molecular genetic studies have established that JA also performs a critical role in several aspects of plant development. Here, we describe the characterization of the Arabidopsis mutant jasmonic acid-hypersensitive1-1 (jah1 1), which is defective in several aspects of JA responses. Although the mutant exhibits increased sensitivity to JA in root growth inhibition, it shows decreased expression of JA-inducible defense genes and reduced resistance to the necrotrophic fungus Botrytis cinerea . Gene cloning studies indicate that these defects are caused by a mutation in the cytochrome P450 protein CYP82C2. We provide evidence showing that the compromised resistance of the jah1-1 mutant to B . cinerea is accompanied by decreased expression of JA-induced defense genes and reduced accumulation of JA-induced indole glucosinolates (IGs). Conversely, the enhanced resistance to B. cinerea in CYP82C2-overexpressing plants is accompanied by increased expression of JA-induced defense genes and elevated levels of JA-induced IGs. We demonstrate that CYP82C2 affects JA-induced accumulation of the IG biosynthetic precursor tryptophan (Trp), but not the JA induced IAA or pathogen-induced camalexin. Together, our results support a hypothesis that CYP82C2 may act in the metabolism of Trp-derived secondary metabolites under conditions in which JA levels are elevated. The jah1-1 mutant should thus be important in future studies toward understanding the mechanisms underlying the complexity of JA-mediated differential responses, which are important for plants to adapt their growth to the ever-changing environments. PMID- 20354504 TI - Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression. AB - The development of leukemia as a consequence of vector-mediated genotoxicity in gene therapy trials for X-linked severe combined immunodeficiency (SCID-X1) has prompted substantial research effort into the design and safety testing of integrating vectors. An important element of vector design is the selection and evaluation of promoter-enhancer elements with sufficient strength to drive reliable immune reconstitution, but minimal propensity for enhancer-mediated insertional mutagenesis. In this study, we set out to explore the effect of promoter-enhancer selection on the efficacy and safety of human immunodeficiency virus-1-derived lentiviral vectors in gammac-deficient mice. We observed incomplete or absent T- and B-cell development in mice transplanted with progenitors expressing gammac from the phosphoglycerate kinase (PGK) and Wiscott Aldrich syndrome (WAS) promoters, respectively. In contrast, functional T- and B cell compartments were restored in mice receiving an equivalent vector containing the elongation factor-1-alpha (EF1alpha) promoter; however, 4 of 14 mice reconstituted with this vector subsequently developed lymphoma. Extensive analyses failed to implicate insertional mutagenesis or gammac overexpression as the underlying mechanism. These findings highlight the need for detailed mechanistic analysis of tumor readouts in preclinical animal models assessing vector safety, and suggest the existence of other ill-defined risk factors for oncogenesis, including replicative stress, in gene therapy protocols targeting the hematopoietic compartment. PMID- 20354505 TI - Regulation of retinal function but nonrescue of vision in RPE65-deficient dogs treated with doxycycline-regulatable AAV vectors. AB - In previous studies, we demonstrated that recombinant adeno-associated virus (rAAV)-mediated gene transfer of the doxycycline (Dox)-regulatable system allows for the regulation of erythropoietin (EPO) expression in the retina of nonhuman primates after intravenous or oral administration of Dox. In addition, it was shown that administrating different amounts of Dox resulted in a dose-response dynamic of transgene expression. Adeno-associated viral gene therapy has raised hope for the treatment of patients with Leber congenital amaurosis, caused by mutations in the retinal pigment epithelium (RPE)-specific gene RPE65. The preliminary results of three clinical trials suggest some improvement in visual function. However, further improvements might be necessary to optimize vision recovery and this means developing vectors able to generate transgene expression at physiological levels. The purpose of this study was to investigate the ability of the Dox-regulatable system to regulate retinal function in RPE65(-/-) Briard dogs. rAAV vectors expressing RPE65 under the control of either the TetOff and TetOn Dox-regulated promoters or the cytomegalovirus (CMV) constitutive promoter were generated and administered subretinally to seven RPE65-deficient dogs. We demonstrate that the induction and deinduction of retinal function, as assessed by electroretinography (ERG), can be achieved using a Dox-regulatable system, but do not lead to any recovery of vision. PMID- 20354507 TI - Prevalence of incidental pancreatic cysts in the adult population on MR imaging. AB - OBJECTIVES: The reporting of incidental pancreatic cystic lesions on cross sectional imaging studies has dramatically increased over the last few years. The prevalence of incidental pancreatic cysts in the adult population, however, is unknown. The aim of our study was to determine the prevalence of incidentally detected pancreatic cysts in the adult population undergoing abdominal magnetic resonance (MR) imaging. METHODS: MR imaging examinations of 616 consecutive patients obtained between January 2001 and February 2002 were retrospectively reviewed by two radiologists and the following information was recorded: the total number of pancreatic cysts; the maximum diameter, location, and characteristics of the largest cyst; documentation of the cyst(s) within the radiology report; and characteristics of the cyst(s) at imaging follow-up. RESULTS: Incidental pancreatic cysts were present in 13.5% (83/616) of patients, with 60% of the cysts being solitary, and 88% of the cysts being simple. Largest cyst mean and median diameters were 7.4 mm (2-24 mm) and 6 mm, respectively. Both the prevalence of pancreatic cysts and the mean size of the largest cyst increased with age (P=0.007, r=0.893 and P=0.003, r=0.929, respectively). Only 31% (26/83) of incidental pancreatic cysts were documented in the radiology report. The mean size of reported pancreatic cysts was larger than those cysts that were not reported (P<0.001). CONCLUSIONS: The prevalence of incidentally detected pancreatic cysts on MR imaging is 13.5%, and increases with age. A majority of these cysts are not reported on MR imaging studies. PMID- 20354506 TI - Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. AB - OBJECTIVES: Isotretinoin is commonly prescribed for the treatment of severe acne. Although cases of inflammatory bowel disease (IBD) have been reported in isotretinoin users, a causal association remains unproven. METHODS: We performed a case-control study using a large insurance claims database. Incident cases of IBD were identified and matched to three controls on the basis of age, gender, geographical region, health plan, and length of enrollment. Isotretinoin exposure was assessed in a 12-month period before case ascertainment. Conditional logistic regression was used to adjust for matching variables. RESULTS: The study population comprised 8,189 cases (3,664 Crohn's disease (CD), 4,428 ulcerative colitis (UC), and 97 IBD unspecified) and 21,832 controls. A total of 60 subjects (24 cases and 36 controls) were exposed to isotretinoin. UC was strongly associated with previous isotretinoin exposure (odds ratio (OR) 4.36, 95% confidence interval (CI): 1.97, 9.66). However, there was no apparent association between isotretinoin and CD (OR 0.68, 95% CI: 0.28, 1.68). Increasing dose of isotretinoin was associated with elevated risk of UC (OR per 20 mg increase in dose: 1.50, 95% CI: 1.08, 2.09). Compared with non-users, the risk of UC was highest in those exposed to isotretinoin for more than 2 months (OR 5.63, 95% CI: 2.10, 15.03). CONCLUSIONS: UC but not CD is associated with previous isotretinoin exposure. Higher dose of isotretinoin seems to augment this risk. Although the absolute risk of developing UC after taking isotretinoin is likely quite small, clinicians prescribing isotretinoin as well as prospective patients should be aware of this possible association. PMID- 20354508 TI - Prompt upper endoscopy is an appropriate initial management in uninvestigated chinese patients with typical reflux symptoms. AB - OBJECTIVES: We sought to investigate the prevalence of clinically significant endoscopic findings (CSEFs) in Chinese patients presenting with uninvestigated typical reflux symptoms in the absence of alarm symptoms, and to evaluate whether prompt endoscopy is an appropriate initial management in these patients. METHODS: Consecutive patients presenting with uninvestigated typical reflux symptoms (i.e., heartburn or acid regurgitation) as chief complaints were recruited for symptom evaluation and upper endoscopy, followed by a 2-week proton pump inhibitor (PPI) therapy. RESULTS: Of 469 patients recruited, CSEFs were observed in 180 (38.4%): 154 (32.8%) with erosive esophagitis (EE), 18 (3.8%) with Barrett's esophagus (BE), 24 (5.1%) with peptic ulcer disease (PUD), and 4 (0.9%) with carcinomas (1 esophageal carcinoma and 3 gastric adenocarcinomas). Multivariate analysis identified that an age >50 years (odds ratio (OR)=1.94, P=0.008), male gender (OR=4.11, P<0.001), being overweight or obese (OR=2.99, P<0.001), and alcohol use (OR=9.96, P<0.001) were independent risk factors for EE; an age >50 years (OR=4.61, P=0.003) and alcohol use (OR=5.50, P=0.003) were independent risk factors for BE; and Helicobacter pylori infection (OR=8.52, P<0.001) and alcohol use (OR=4.08, P=0.004) were independent risk factors for PUD. Symptom evaluation and response to PPI treatment were not correlated with EE, BE, and PUD in these patients. CONCLUSIONS: CSEFs other than gastroesophageal reflux disease are present in a considerable proportion of Chinese patients with uninvestigated typical reflux symptoms but without alarm features. Symptom evaluation is of limited practical value, and thus prompt endoscopy seems to be an appropriate initial management option in these patients. PMID- 20354509 TI - Prevalence and predictors of appropriate colorectal cancer surveillance in Lynch syndrome. AB - OBJECTIVES: Lynch syndrome (LS) is a hereditary cancer syndrome that conveys a high risk of colorectal cancer (CRC). Guidelines recommend colonoscopy every 1 to 2 years. There is limited information about screening compliance in this high risk group. METHODS: Data about cancer screening behaviors were obtained from subjects recruited through four US cancer genetics clinics. The main outcome was prevalence of appropriate CRC surveillance for LS. RESULTS: A total of 181 individuals had a family history that met the Amsterdam criteria for LS (n=154) and/or had an identified mutation in a mismatch repair (MMR) gene (n=105). Of these 181 individuals, 131 (73%) had appropriate LS surveillance with colonoscopies at least every 2 years for their age >25 years. Of those with inadequate surveillance, 26/49 (53%) had colonoscopies at 3- to 5-year intervals. There were no significant differences in health-care setting, perceived risk of CRC, or compliance with screening for other cancers. Rates of appropriate surveillance were higher among individuals who had been referred for genetic evaluation for LS compared with those who had not (109/136 (80%) vs. 23/45 (51%), respectively, P=0.0004). In multivariate analysis, personal history of CRC (odds ratio (OR) 2.81), having a first-degree relative with CRC at age <50 years (OR 2.61), and having undergone a genetic evaluation (OR 4.62) were associated with appropriate CRC surveillance for LS. CONCLUSIONS: The time between colonoscopic exams in patients with LS is often longer than recommended by current guidelines and may place them at risk for interval cancers. Recognizing clinical features of LS and providing genetic counseling, evaluation, and intensive surveillance may improve cancer prevention for those at the highest risk for CRC. PMID- 20354510 TI - Hormone replacement therapy, oral contraceptive use, and distal large bowel cancer: a population-based case-control study. AB - OBJECTIVES: Lower incidence rates of distal large bowel cancer in women when compared with men support the protective role of female hormones. We aimed to determine the associations between hormone replacement therapy, oral contraceptive use, and distal large bowel cancer. METHODS: We conducted a population-based case-control study of incident distal large bowel cancer in North Carolina between 2001 and 2006. Data on hormone replacement therapy, oral contraceptive use, demographics, and risk factors were obtained through in-person interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between oral contraceptive use, hormone replacement therapy, and distal large bowel cancer were estimated through unconditional logistic regression models overall, by duration of use, and within strata of race. RESULTS: There were a total of 443 women with distal large bowel cancer and 405 controls. Ever use of hormone replacement therapy was strongly associated with a reduced risk of distal large bowel cancer (OR 0.52, 95% CI 0.38-0.72). Further reduction of distal large bowel cancer risk occurred with increased duration of use (<4 years (OR 0.77, 95% CI 0.44-1.35), 4-8 years (OR 0.64, 95% CI 0.37-1.10), 9-14 years (OR 0.47, 95% CI 0.27-0.81), and >or=15 years (OR 0.34, 95% CI 0.20 0.58)). Ever use of oral contraceptives was not associated with reduced incidence of distal large bowel cancer (OR 0.95, 95% CI 0.67-1.34) nor was duration of use. There were no differences by race. CONCLUSIONS: Hormone replacement therapy is associated with a lower risk of distal large bowel cancer. This risk is further reduced with increased duration of use. Hormone replacement therapy may be partially responsible for the reduced incidence of distal large bowel cancer in women compared with men. PMID- 20354511 TI - Predicting causal effects in large-scale systems from observational data. PMID- 20354512 TI - A method and server for predicting damaging missense mutations. PMID- 20354513 TI - Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. PMID- 20354514 TI - Laser tricks without labels. AB - Nonlinear optical microscopy lets researchers see chemical composition in living cells and organisms. PMID- 20354516 TI - Not all noise is waste. AB - Stochastic profiling, a method to rank heterogeneity of gene expression in a cell population, shows that quantifying cell-to-cell variability has come of age and leads to biological insight. PMID- 20354515 TI - The 'when and whereabouts' of injected pathogen effectors. AB - Tracking the spatiotemporal dynamics of bacterial effectors injected into single living host cells has become possible with a split GFP-based method. PMID- 20354517 TI - Toward atomic accuracy in RNA design. AB - The introduction of new and accurate force fields for atom-atom interactions into the Rosetta framework allows the recovery of native-like RNA structures. PMID- 20354519 TI - Long-term follow-up of cervical disease in women screened by cytology and HPV testing: results from the HART study. AB - BACKGROUND: Several studies have shown that testing for high-risk human papillomavirus (HPV) types results in an improved sensitivity for CIN2+, compared with cytology, although with a somewhat lower specificity. METHODS: We obtained follow-up results, with at least one smear after participation in the HART study, which compared HPV testing (HC-II) with cytology as a primary screening modality. RESULTS: With a median follow-up of 6 years, 42 additional cases of CIN2+ were identified; women who were HPV positive at baseline were more likely to develop CIN2+ than those who were HPV negative (hazard ratio (HR) 17.2; 95% confidence interval (CI) (9.3-31.6)) and the risk increased with increasing viral load. Compared with HPV-negative women (relative light unit (RLU) <1), the HR (95% CI) was 5.4 (1.6, 18.2) for 1-10 RLU and 25.5 (13.6, 47.9) for RLU > or = 10. Positive cytology (borderline or worse compared with negative) was also predictive of developing CIN2, although to a lesser extent (HR 8.7; 95% CI (4.5 17.1)). Only one case of CIN3 and three cases of CIN2 were found in women who showed a positive cytology result but were HPV negative at baseline. CONCLUSION: After 5 years of follow-up, CIN2+ occurred in 0.23% of women who were HPV negative at baseline compared with 0.48% of women who showed a negative cytology result, indicating a much longer low-risk interval for CIN2+ after HPV testing. PMID- 20354518 TI - Probing cellular events, one quantum dot at a time. AB - Monitoring the behavior of single molecules in living cells is a powerful approach to investigate the details of cellular processes. Owing to their optical, chemical and biofunctional properties, semiconductor quantum dot (QD) probes promise to be tools of choice in this endeavor. Here we review recent advances that allow ever more controlled experiments at the single-nanoparticle level in live cells. Several examples, related to membrane dynamics, cell signaling or intracellular transport, illustrate how single QD tracking can be readily used to decipher complex biological processes and address key concepts that underlie cellular organization and dynamics. PMID- 20354520 TI - Age of mother and grandmother in relation to a subject's breast cancer risk. AB - BACKGROUND: On theoretical grounds, the age of the grandmother and the age of the mother at delivery of her daughter may affect the breast cancer risk of the granddaughter. METHODS: We used the data relating to the Diagnostic Research Mamma-carcinoma cohort (DOM (Diagnostisch Onderzoek Mammacarcinoom) 3), which comprises a population-based sample of 12 178 women aged 41-63 years at enrolment in 1982-85 and followed up until 2000. During follow-up 340 postmenopausal breast cancer cases were identified. To these we applied a case-cohort design together with a random sample from the baseline cohort (n=1826). Of these study participants, we were able to retrieve the birth dates of 998 mothers (309 cases, 689 controls), and for 547 of these we also retrieved the birth dates of the grandmothers (197 cases, 350 controls). A weighted Cox proportional hazards model was used to estimate the hazard ratios (HRs) for the effect of the age of the grandmother and the age of the mother on the breast cancer risk of the index women, while adjusting for potential confounders. RESULTS: Compared with the reference group aged 25-29.9 years, the group with the lowest maternal age (<25 years) had an age-adjusted HR of 0.77 (95% CI 0.19-3.12) and the group with the highest maternal age (> or = 40 years) had an age-adjusted HR of 1.58 (95% CI 0.01-267.81), P-value for trend=0.62. Compared with the same reference group, the group with the lowest grandmaternal age (<25 years) had an age-adjusted HR of 0.53 (95% CI 0.24-1.17) and the group with the highest grandmaternal age (> or = 40 years) had an age-adjusted HR of 7.29 (95% CI 1.20-44.46), P for trend=0.04. The associations did not change significantly after additional adjustment for various risk factors for breast cancer, neither for maternal age nor for grandmaternal age. CONCLUSION: This study does not suggest a major role of maternal age at delivery or grandmaternal age at delivery of the mother for the (grand)daughters' breast cancer risk. PMID- 20354521 TI - Cancer risk in patients hospitalised for Graves' disease: a population-based cohort study in Sweden. AB - BACKGROUND: The possibility of an association of Graves' disease (GD) with subsequent cancers raised by certain studies. METHODS: Using a database on 18 156 hospitalised GD patients, subsequent cancers were ascertained. RESULTS: Increased risks of thyroid and parathyroid tumours were limited to the early follow-up period, which is probably a surveillance bias. Cancer sites with observed excess included the mouth and breast, in contrast to decreased risks of colon cancer, melanoma and non-Hodgkin's lymphoma. CONCLUSION: Increased subsequent cancers in GD patients appeared to be balanced by decreased risks at other sites; chance cannot be excluded. PMID- 20354522 TI - Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care. AB - BACKGROUND: To evaluate the antitumour activity and safety of metronomic cyclophosphamide vs megestrol acetate in progressive and advanced cancer patients having exhausted all effective therapies under standard care. METHODS: Patients were randomly assigned to receive orally metronomic cyclophosphamide (50 mg b.i.d) or megestrol acetate (160 mg only daily) until intolerance or progression (RECIST 1.0). The primary efficacy end point was a 2-month progression-free rate (PFR(2m)). According to Optimal Simon's design and the following assumptions, namely, P0=5%, P1=20%, alpha=beta=10%, the treatment is considered as effective if atleast 5 out of 44 patients achieved PFR(2m). RESULTS: Between September 2006 and January 2009, 88 patients were enrolled. Two patients experienced grade 3-4 toxicities in each arm (4%). One toxic death occurred in the megestrol acetate arm as a consequence of thrombosis. The metronomic cyclophosphamide arm reached the predefined level of efficacy with a PFR(2m) rate of 9 out of 44 and a PFR(4m) rate of 5 out of 44. The MA arm failed to achieve the level of efficacy with a PFR(2m) of 4 out of 44 and a PFR(4m) of 1 out of 44. The median overall survival was 195 and 144 days in the metronomic cyclophosphamide arm and megestrol acetate arm, respectively. CONCLUSION: Metronomic cyclophosphamide is well tolerated and provides stable disease in such vulnerable and poor-prognosis cancer patients. This regimen warrants further evaluations. PMID- 20354523 TI - Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer. AB - BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR-KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3' untranslated region (UTR), pMIR KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR-KLK10 and either let-7f, miR-224, or mR 516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR 516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSION: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required. PMID- 20354524 TI - Oncogenic KRAS sensitises colorectal tumour cells to chemotherapy by p53 dependent induction of Noxa. AB - BACKGROUND: Oxaliplatin and 5-fluorouracil (5-FU) currently form the backbone of conservative treatment in patients with metastatic colorectal cancer. Tumour responses to these agents are highly variable, but the underlying mechanisms are poorly understood. Our previous results have indicated that oncogenic KRAS in colorectal tumour cells sensitises these cells to chemotherapy. METHODS: FACS analysis was used to determine cell-cycle distribution and the percentage of apoptotic and mitotic cells. A multiplexed RT-PCR assay was used to identify KRAS controlled apoptosis regulators after exposure to 5-FU or oxaliplatin. Lentiviral expression of short-hairpin RNAs was used to suppress p53 or Noxa. RESULTS: Oncogenic KRAS sensitised colorectal tumour cells to oxaliplatin and 5-FU in a p53-dependent manner and promoted p53 phosphorylation at Ser37 and Ser392, without affecting p53 stabilisation, p21 induction, or cell-cycle arrest. Chemotherapy-induced expression of the p53 target gene Noxa was selectively enhanced by oncogenic KRAS. Suppression of Noxa did not affect p21 induction or cell-cycle arrest, but reduced KRAS/p53-dependent apoptosis after exposure to chemotherapy in vitro and in tumour xenografts. Noxa suppression did not affect tumour growth per se, but strongly reduced the response of these tumours to chemotherapy. CONCLUSION: Oncogenic KRAS determines the cellular response to p53 activation by oxaliplatin or 5-FU, by facilitating apoptosis induction through Noxa. PMID- 20354525 TI - Predicting the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding: the Norwich DEFAB risk assessment tool. AB - BACKGROUND: This study aimed to show the longitudinal use of routinely collected clinical data from history and ultrasound evaluation of the endometrium in developing an algorithm to predict the risk of endometrial carcinoma for postmenopausal women presenting with vaginal bleeding. METHODS: This prospective study collected data from 3047 women presenting with postmenopausal bleeding. Data regarding the presence of risk factors for endometrial cancer was collected and univariate and multivariate analyses were performed. RESULTS: Age distribution ranged from 35 to 97 years with a median of 59 years. A total of 149 women (5% of total) were diagnosed with endometrial carcinoma. Women in the endometrial cancer group were significantly more likely to be older, have higher BMI, recurrent episodes of bleeding, diabetes, hypertension, or a previous history of breast cancer. An investigator best model selection approach was used to select the best predictors of cancer, and using logistic regression analysis we created a model, 'Norwich DEFAB', which is a clinical prediction rule for endometrial cancer. The calculated Norwich DEFAB score can vary from a value of 0 to 9. A Norwich DEFAB value equal to or greater than 3 has a positive predictive value (PPV) of 7.78% and negative predictive value (NPV) of 98.2%, whereas a score equal to or greater than 5 has a PPV of 11.9% and NPV of 97.8%. CONCLUSION: The combination of clinical information with our investigation tool for women with postmenopausal vaginal bleeding allows the clinician to calculate a predicted risk of endometrial malignancy and prioritise subsequent clinical investigations. PMID- 20354526 TI - Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors. PMID- 20354527 TI - Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant. AB - BACKGROUND: Ovarian cancer is the most lethal gynaecological malignancy. Although ovarian cancer patients often respond initially to chemotherapy, they usually develop chemoresistance. We hypothesised that a small portion of ovarian cancer cells have stem-like cell properties that contribute to tumourigenesis and drug resistance. METHODS: Flow cytometry and Hoechst 33342 efflux isolated side population (SP) cells from ascites derived from ovarian cancer patients and from mice inoculated with human ovarian cancer cell lines. The SP cells were examined for stem cell markers OCT4, NANOG, STELLAR, and ABCG2/BCRP1 by immunocytochemistry and RT-PCR. The SP cells and non-SP cells were studied for tumourigenesis and chemoresistance in vitro and in vivo. RESULTS: The SP cells expressed ABCG2/BCRP1, OCT4, STELLAR, and NANOG, detected by immunocytochemistry and RT-PCR. ABCG2/BCRP1 expression was higher in SP than in non-SP cells. Xenogeneic mice inoculated with SP cells yielded more tumours than did mice inoculated with non-SP cells. In parallel, SP cell culture resulted in extensive cell proliferation, which was markedly more than in non-SP cells. SP cells resisted chemotherapy compared with non-SP cells, both in vivo and in vitro. CONCLUSION: Ovarian cancer SP cells are tumourigenic and chemoresistant. ABCG2/BCRP1 has an important role in chemoresistance, which has implications for new therapeutic approaches. PMID- 20354530 TI - The definition of locally advanced pancreatic cancer. PMID- 20354531 TI - Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). AB - BACKGROUND: The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years. METHODS: A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007. RESULTS: Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5-32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3-19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years. CONCLUSIONS: The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies. PMID- 20354532 TI - Risks of second primary cancer among patients with major histological types of lung cancers in both men and women. AB - BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC. PMID- 20354535 TI - Roles of small regulatory RNAs in determining neuronal identity. AB - Neurogenesis, the process of generating functional neurons from neural stem cells, is tightly controlled by many intrinsic and extrinsic mechanisms. Uncovering these regulatory mechanisms is crucial for understanding the functions and plasticity of the human brain. Recent studies in both invertebrates and vertebrates point to the importance of small regulatory RNAs in regulating lineage-specific gene expression and determining neuronal identity during neurogenesis. These new observations suggest that small regulatory RNAs could function at many levels to regulate self-renewal of neural stem cells and neuronal fate specification, implicating small regulatory RNAs in the complexity of neurogenesis. PMID- 20354534 TI - New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? AB - The integration of adult-born neurons into the circuitry of the adult hippocampus suggests an important role for adult hippocampal neurogenesis in learning and memory, but its specific function in these processes has remained elusive. In this article, we summarize recent progress in this area, including advances based on behavioural studies and insights provided by computational modelling. Increasingly, evidence suggests that newborn neurons might be involved in hippocampal functions that are particularly dependent on the dentate gyrus, such as pattern separation. Furthermore, newborn neurons at different maturation stages may make distinct contributions to learning and memory. In particular, computational studies suggest that, before newborn neurons are fully mature, they might function as a pattern integrator by introducing a degree of similarity to the encoding of events that occur closely in time. PMID- 20354537 TI - A breakthrough in Hodgkin's disease. PMID- 20354536 TI - Spatial organization and signal transduction at intercellular junctions. AB - The coordinated organization of cell membrane receptors into diverse micrometre scale spatial patterns is emerging as an important theme of intercellular signalling, as exemplified by immunological synapses. Key characteristics of these patterns are that they transcend direct protein-protein interactions, emerge transiently and modulate signal transduction. Such cooperativity over multiple length scales presents new and intriguing challenges for the study and ultimate understanding of cellular signalling. As a result, new experimental strategies have emerged to manipulate the spatial organization of molecules inside living cells. The resulting spatial mutations yield insights into the interweaving of the spatial, mechanical and chemical aspects of intercellular signalling. PMID- 20354539 TI - Radiotherapy: Neurocognitive considerations in the treatment of brain metastases. AB - The results of a randomized, controlled trial investigating the neurocognitive effects of stereotactic radiosurgery (SRS), with or without whole-brain radiation therapy (WBRT), to treat brain metastases demonstrated a significant reduction in learning and memory, associated with the addition of WBRT to SRS. the results indicate that SRS monotherapy is an effective and safe initial management strategy for brain metastases. PMID- 20354540 TI - Medical oncology: Zoledronic acid for breast cancer therapy-induced bone loss. AB - The addition of zoledronic acid to aromatase inhibitors is associated with improved bone mineral density, but not with an effect on clinically-meaningful end points such as fractures. The oncology community should prioritize the design of trials evaluating more relevant end points, such as fragility fracture risk, for treatment-induced bone loss and critically assess the effects of such treatment on breast cancer survival. PMID- 20354541 TI - Radiotherapy: PSA nadir predicts long-term mortality. AB - The effect of PSA level on distant metastases and cause-specific mortality was assessed in a recent study, and showed a nadir PSA level 1.5 ng/ml within 2 years of radiotherapy treatment predicts distant metastases and death from prostate cancer. PMID- 20354542 TI - Chemotherapy: How useful is adjuvant irinotecan in stage IV CRC? AB - Patients who undergo hepatic surgery for initially resectable liver metastases from colorectal cancer have a 70% risk of relapse. a recent phase III randomized trial has failed to demonstrate an improvement in disease-free survival with the addition of irinotecan to 5-fluorouracil and folinic acid as adjuvant treatment for patients with radically resected colorectal cancer with liver metastases. PMID- 20354543 TI - Chemotherapy: Current drugs still have potential in advanced ovarian cancer. AB - Dose-dense administration of paclitaxel as well as intraperitoneal administration of platinum and paclitaxel as first-line treatments provide similar advantages compared with standard treatment in advanced ovarian cancer. Both approaches, however, need to be confirmed by additional studies. a low dose of pegylated liposomal doxorubicin combined with carboplatin is superior to standard paclitaxel and carboplatin in relapsed platinum-sensitive ovarian cancer. PMID- 20354544 TI - Imaging: Mass spectrometry in HNSCC--a peek at response prediction? AB - EGFR inhibitors provide benefit in patients with advanced and metastatic head and neck squamous cell carcinoma (HNSCC). Mass spectrometry profiling has been used to predict outcome in patients with HNSCC after EGFR inhibitor treatment, and may enable prior identification of patients most likely to benefit from these therapies. however, further validation in prospective studies is needed. PMID- 20354549 TI - Urinary liver fatty acid-binding protein: another novel biomarker of acute kidney injury. AB - Liver fatty acid-binding protein (L-FABP) binds selectively to intracellular free unsaturated fatty acids and lipid peroxidation products during hypoxic tissue injury. Urinary L-FABP is a potential biomarker for the detection and assessment of acute kidney injury (AKI). Ferguson et al. have demonstrated in a cross sectional study that urinary L-FABP is an excellent biomarker of AKI and may be useful in predicting dialysis-free survival. This study did not assess utility for early diagnosis of AKI. PMID- 20354546 TI - Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood-brain barrier dysfunction in vivo. AB - Hemoglobin (Hb) released from extravasated erythrocytes is implicated in brain edema after intracerebral hemorrhage (ICH). Hemoglobin is a major component of blood and a potent mediator of oxidative stress after ICH. Oxidative stress and matrix metalloproteinases (MMPs) are associated with blood-brain barrier (BBB) dysfunction. This study was designed to elucidate whether Hb-induced oxidative stress contributes to MMP-9 activation and BBB dysfunction in vivo. An intracerebral injection of Hb into rat striata induced increased hydroethidine (HEt) signals in parallel with MMP-9 levels. In situ gelatinolytic activity colocalized with oxidized HEt signals in vessel walls, accompanied by immunoglobulin G leakage and a decrease in immunoactivity of endothelial barrier antigen, a marker of endothelial integrity. Administration of a nonselective MMP inhibitor prevented MMP-9 levels and albumin leakage in injured striata. Moreover, reduction in oxidative stress by copper/zinc-superoxide dismutase (SOD1) overexpression reduced oxidative stress, MMP-9 levels, albumin leakage, and subsequent apoptosis compared with wild-type littermates. We speculate that Hb-induced oxidative stress may contribute to early BBB dysfunction and subsequent apoptosis, partly through MMP activation, and that SOD1 overexpression may reduce Hb-induced oxidative stress, BBB dysfunction, and apoptotic cell death. PMID- 20354545 TI - Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials? AB - Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke. PMID- 20354550 TI - A role for novel cell-cycle proteins in podocyte biology. AB - Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell types affected include both tubular and glomerular compartments. Now a novel cell cycle-related protein is shown to influence podocyte biology. PMID- 20354552 TI - The hypothesis that bone turnover influences FGF23 secretion. PMID- 20354554 TI - Assessment of acid-base disorders. PMID- 20354556 TI - Acute kidney injury and long-term outcomes: more to learn. PMID- 20354557 TI - Renal allograft loss due to overwhelming invasive Candida infection. PMID- 20354558 TI - Estimation of abdominal fat compartments by bioelectrical impedance: the validity of the ViScan measurement system in comparison with MRI. AB - BACKGROUND/OBJECTIVES: Abdominal obesity, more specifically increased intra abdominal adipose tissue, is strongly associated with increased risk of metabolic disease. Bioelectrical impedance analysis (BIA) has been proposed as a potential method of determining individual abdominal fat compartments in the form of the commercially available ViScan measurement system (Tanita Corporation), but it has yet to be independently validated. The objective of this study was to analyse the validity of the ViScan to assess adult abdominal adiposity across a range of body fatness. SUBJECTS/METHODS: This was a cross-sectional study with 74 participants (40 females and 34 males with body mass index (BMI) between 18.5 and 39.6 kg/m(2)). Total abdominal adipose tissue, subcutaneous abdominal adipose tissue (SAAT) and intra-abdominal adipose tissue (IAAT) were measured by magnetic resonance imaging (MRI). In addition, intra-hepatocellular lipid was obtained by magnetic resonance spectroscopy. Estimates of abdominal adiposity (total and compartmental) were obtained from BIA and anthropometry. RESULTS: ViScan-derived percentage trunk fat strongly and significantly related with total abdominal adipose tissue and SAAT in both lean and overweight/obese individuals, and categorized individuals reliably in terms of total abdominal fat. ViScan-derived 'visceral' fat correlated significantly with IAAT but the strength of this relationship was much weaker in overweight/obese individuals, particularly those with higher SAAT, leading to less reliable classification of individuals for IAAT. CONCLUSIONS: The ViScan may serve as a useful tool for predicting total abdominal fat, but prediction of visceral fat (IAAT) may be limited, especially in abdominally obese individuals. PMID- 20354559 TI - The effect of nutritional supplementation on physical activity and exploratory behavior of Mexican infants aged 8-12 months. AB - BACKGROUND/OBJECTIVES: Physical activity and exploration in infancy affect physical and cognitive development. Nutritional supplementation improves activity in severely malnourished infants, but the evidence in mild-to-moderately malnourished and nutritionally at-risk infants is equivocal. We tested the effect of multiple-micronutrient supplementation on physical activity and exploration in Mexican infants. SUBJECTS/METHODS: Using a quasi experimental design, we analyzed data from a supplementation study that lacked a placebo-control group. We compared infants between 8 and 12 months measured at baseline who had received no supplementation (comparison group, n=78), with infants 8-12 months measured after 4 months of daily supplementation (treatment group, n=109). The treatment consisted of three supplement types: micronutrient powder, syrup (each containing only micronutrients) and a milk-based, fortified-food supplement (FFS; containing micronutrients and macronutrients). We formed the micronutrient-only group (MM) by combining the micronutrient powder and syrup groups. We measured activity and exploration by direct observation and used cluster analysis to form and characterize activity and exploration clusters. We performed logistic regression with activity or exploration cluster as the outcome variable and treatment versus comparison and MM or FFS versus comparison as the predictor variables. RESULTS: Treatment versus comparison increased the odds of being in the high activity (odds ratio (OR)=2.35, P<0.05) and high exploration (OR=1.87, P<0.05) cluster. MM increased the odds of being in the high activity (OR=2.64, P<0.05) cluster and FFS increased the odds (OR=3.16, P<0.05) of being in the high exploration cluster. CONCLUSIONS: Nutritional supplementation benefited activity and exploration in this sample of Mexican infants. PMID- 20354560 TI - Association between the frequency of fruit and vegetable consumption and cardiovascular disease in male smokers and non-smokers. AB - BACKGROUND/OBJECTIVES: Consumption of fruit and vegetables (F&V) is associated with a lower cardiovascular disease (CVD) risk. Smoking may affect the strength of this association. The objective of this study was to compare the relationship between the frequency of F&V intake and CVD risk in male current, former and never smokers. SUBJECTS/METHODS: A prospective study in men (n=8060) aged 50-59 years who were recruited in France and Northern Ireland. The frequency of F&V intake was assessed by using a food frequency questionnaire. The outcome criteria were incident cases of acute coronary syndrome (ACS) and total CVD (coronary heart disease and stroke) over 10-year period. RESULTS: A total of 367 ACS and 612 CVD events occurred during the follow-up period. A multivariate analysis revealed a statistically significant interaction between smoking status and F&V intake for ACS and for CVD (both P's<0.05). In current smokers, the relative risks for ACS were 0.78 (0.54-1.13) and 0.49 (0.30-0.81) in the second and third tertiles of F&V intake, respectively (P for trend<0.001); for CVD, the values were 0.80 (0.59-1.08) and 0.64 (0.44-0.93) respectively (P for trend<0.001). In contrast, no statistically significant associations were observed for never and former smokers. Similar statistical interactions for ACS were observed for fruit intake (P=0.07) and vegetable intake (P<0.05) taken separately. CONCLUSIONS: These results suggest that high fruit and vegetable intake is associated with a lower risk of CVD in male smokers. PMID- 20354561 TI - Detection of susceptibility genes as modifiers due to subgroup differences in complex disease. AB - Complex diseases invariably involve multiple genes and often exhibit variable symptom profiles. The extent to which disease symptoms, course, and severity differ between affected individuals may result from underlying genetic heterogeneity. Genes with modifier effects may or may not also influence disease susceptibility. In this study, we have simulated data in which a subset of cases differ by some effect size (ES) on a quantitative trait and are also enriched for a risk allele. Power to detect this 'pseudo-modifier' gene in case-only and case control designs was explored blind to case substructure. Simulations involved 1000 iterations and calculations for 80% power at P<0.01 while varying the risk allele frequency (RAF), sample size (SS), ES, odds ratio (OR), and proportions of the case subgroups. With realistic values for the RAF (0.20), SS (3000) and ES (1), an OR of 1.7 is necessary to detect a pseudo-modifier gene. Unequal numbers of subjects in the case groups result in little decrement in power until the group enriched for the risk allele is <30% or >70% of the total case population. In practice, greater numbers of subjects and selection of a quantitative trait with a large range will provide researchers with greater power to detect a pseudo modifier gene. However, even under ideal conditions, studies involving alleles with low frequencies or low ORs are usually underpowered for detection of a modifier or susceptibility gene. This may explain some of the inconsistent association results for many candidate gene studies of complex diseases. PMID- 20354562 TI - Early onset and slow progression of SCA28, a rare dominant ataxia in a large four generation family with a novel AFG3L2 mutation. AB - Autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders primarily affecting the cerebellum. Genetically, 26 different loci have been identified so far, although the corresponding gene has not yet been determined for 10 of them. Recently, mutations in the ATPase family gene 3-like 2 gene were presented to cause SCA type 28. To define the frequency of SCA28 mutations, we performed molecular genetic analyses in 140 unrelated familial cases with ataxia. Among other variations, we found a novel missense mutation at an evolutionarily conserved amino-acid position using a single-strand conformation polymorphism approach, followed by DNA sequencing. This amino-acid exchange p.E700K was detected in a four-generation German family and was not observed in a survey of 400 chromosomes from healthy control individuals. PMID- 20354563 TI - Linkage disequilibrium and age of HLA region SNPs in relation to classic HLA gene alleles within Europe. AB - The HLA region on chromosome 6 is gene-rich and under selective pressure because of the high proportion of immunity-related genes. Linkage disequilibrium (LD) patterns and allele frequencies in this region are highly differentiated across broad geographical populations, making it a region of interest for population genetics and immunity-related disease studies. We examined LD in this important region of the genome in six European populations using 166 putatively neutral SNPs and the classical HLA-A, -B and -C gene alleles. We found that the pattern of association between classic HLA gene alleles and SNPs implied that most of the SNPs predated the origin of classic HLA gene alleles. The SNPs most strongly associated with HLA gene alleles were in some cases highly predictive of the HLA allele carrier status (misclassification rates ranged from <1 to 27%) in independent populations using five or fewer SNPs, a much smaller number than tagSNP panels previously proposed and often with similar accuracy, showing that our approach may be a viable solution to designing new HLA prediction panels. To describe the LD within this region, we developed a new haplotype clustering method/software based on r(2), which may be more appropriate for use within regions of strong LD. Haplotype blocks created using this proposed method, as well as classic HLA gene alleles and SNPs, were predictive of a northern versus southern European population membership (misclassification error rates ranged from 0 to 23%, depending on which independent population was used for prediction), indicating that this region may be a rich source of ancestry informative markers. PMID- 20354564 TI - Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city. AB - Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are used extensively in personal care products, including fragrances (DEP) and nail polish (DnBP). Between May 2003 and July 2006, we gathered questionnaire data on the use of seven product categories (deodorant, perfume, hair spray, hair gel, nail polish/polish remover, liquid soap/body wash, and lotion/mist) over 48 h during the third trimester of pregnancy from 186 inner-city women. A 48-h personal air sample was collected and analyzed for DEP and DnBP; a maternal spot urine sample was collected and analyzed for their monoester metabolites, monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), respectively. In all, 97% of air samples and 84% of urine samples were collected within +/-2 days of the questionnaire. During the 48 h, 41% of women reported perfume use and 10% reported nail polish/polish remover use. In adjusted analyses, no association was seen between nail product use and air DnBP or urine MnBP concentrations. Women reporting perfume use had 2.3 times higher (95% CI 1.6, 3.3) urinary MEP concentrations. Personal air DEP increased by 7% for each 25% increase in a composite indicator of the six other product categories (P<0.05), but was not associated with perfume use. Air DEP was correlated with urine MEP concentrations only among non-perfume users (r=0.51, P<0.001). Results suggest that perfume use is a significant source of DEP exposure. PMID- 20354565 TI - Dietary patterns among the Metro Atlanta Cohort: implications for population based longitudinal dietary pesticide exposure and risk assessment. AB - Characterizing dietary consumption patterns is critical to dietary pesticide exposure assessment. We compared consumption patterns between adults (age 18-60) in the Metro Atlanta Cohort (MAC), a longitudinal study of pesticide exposure among Atlanta residents, and US National Health and Nutrition Examination Survey (NHANES) adults. We focused on foods commonly eaten by US adults and foods likely to contain certain pesticide residues. MAC participants provided consumption data for 6 days per month for 1 year using a web-based data collection tool. We defined "percent eaters" as the percent of participants who reported eating a particular food in 24 h. We computed the NHANES weighted percent eaters and 95% confidence limits (CLs) using the 24-h dietary recall data. We calculated the MAC percent eaters for each sampling day and the percent of days this number fell below, within, or above the NHANES 95% CLs. We also re-sampled the MAC percent eaters across sampling days to find whether the resulting distribution resembled the NHANES estimate, and used the Kruskal-Wallis test to evaluate whether season affected the number of MAC eaters of a particular food on a given sampling day. In general, across all sampling days, a greater proportion of MAC participants reported eating banana, broccoli, cream, grapes, lettuce, onion, peach, pear, peas, strawberries, string beans, and tomatoes than the national estimate, whereas the proportion of apple, spinach, ketchup and white bread/roll eaters was similar, and the proportion of milk drinkers was lower. Season predicted the number of MAC peach and strawberry eaters but not other foods. The data show how a higher proportion of Atlanta adults may eat certain foods (e.g., peaches in summer or strawberries in spring) than the national average depending on season or other factors. An exposure assessment that ignored this difference could underestimate dietary pesticide intakes. PMID- 20354567 TI - Hepatic Retransplantation. PMID- 20354566 TI - Another treatment gap: restarting secondary prevention medications: the Women's Health Initiative. AB - BACKGROUND: Women's long-term patterns of evidence-based preventive medication utilization following a coronary heart disease (CHD) diagnosis have not been sufficiently studied. METHODS: Postmenopausal women 50-79 years were eligible for randomization in the Women's Health Initiative's (WHI) hormone trials if they met inclusion and exclusion criteria and were >80% adherent during a placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20% fat diet. Those with adjudicated myocardial infarction or coronary revascularization after the baseline visit were included in the analysis (n=2627). Baseline visits occurred between 1993 and 1998, then annually until the trials ended in 2002 through 2005; medication inventories were obtained at baseline and years 1, 3, 6 and 9. RESULTS: Utilization at the first WHI visit following a CHD diagnosis increased over time for statins (49% to 72%; p<0.0001), beta-blockers (49% to 62%; p=0.003), and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEI/ARBs ) [26 to 43%; p<0.0001]. Aspirin use remained stable at 76% (p=0.09). Once women reported using a statin, aspirin, or beta-blocker, 84-89% reported use at 1 or more subsequent visits, with slightly lower rates for ACEI/ARBS (76%). Statin, aspirin, beta-blocker, or ACEI/ARB use was reported at 2 or more consecutive visits by 57%, 66%, 48%, and 28% respectively. These drugs were initiated or resumed at a later visit by 24%, 17%, 15%, and 17%, respectively, and were never used during the period of follow up by 19%, 10%, 33%, and 49% respectively. CONCLUSIONS: Efforts to improve secondary prevention medication utilization should target both drug initiation and restarting drugs in patients who have discontinued them. PMID- 20354568 TI - INSIG2 is Associated with Lower Gain in Weight-for-Length Between Birth and Age 6 Months. AB - Researchers have described the association of a common DNA polymorphism, rs7566605, near INSIG2 (insulin-induced gene 2) with obesity in multiple independent populations that include subjects ages 11-60 years.1 To our knowledge, no studies have examined the association of this polymorphism with weight status during early childhood. We explored the association of the rs7566605 polymorphism with weight-for-length among 319 children at 6 months and 3 years participating in Project Viva, a pre-birth cohort study. In contrast to studies of older individuals, CC homozygosity was associated with lower gain in weight-for-length z-score between birth and age 6 months than GG homozygosity or GC heterozygosity. At age 3, we did not find an association. The association of INSIG2 gene with obesity may change direction with age. PMID- 20354569 TI - Cardiac-restricted overexpression of the A(2A)-adenosine receptor in FVB mice transiently increases contractile performance and rescues the heart failure phenotype in mice overexpressing the A(1)-adenosine receptor. AB - In the heart, adenosine binds to pharmacologically distinct G-protein-coupled receptors (A(1)-R, A(2A)-R, and A(3)-R). While the role of A(1)- and A(3)-Rs in the heart has been clarified, the effect of genetically manipulating the A(2A)-R has not been defined. Thus, we created mice overexpressing a cardiac-restricted A(2A)-R transgene. Mice with both low (Lo) and high (Hi) levels of A(2A)-R overexpression demonstrated an increase in cardiac contractility at 12 weeks. These changes were associated with a significantly higher systolic but not diastolic [Ca(2+)]i, higher maximal contraction amplitudes, and a significantly enhanced sarcoplasmic reticulum Ca(2+) uptake activity. At 20 weeks, the effects of A(2A)-R overexpression on cardiac contractility diminished. The positive effects elicited by A(2A)-R overexpression differ from the heart failure phenotype we observed with A(1)-R overexpression. Interestingly, coexpression of A(2A)-R TG(Hi), but not A(2A)-R TGLo, enhanced survival, prevented the development of left ventricular dysfunction and heart failure, and improved Ca(2+) handling in mice overexpressing the A(1)-R. These results suggest that adenosine-mediated signaling in the heart requires a balance between A(1)- and A(2A)-Rs--a finding that may have important implications for the ongoing clinical evaluation of adenosine receptor subtype-specific agonists and antagonists for the treatment of cardiovascular diseases. PMID- 20354570 TI - School Context and the Effect ESL Placement on Mexican-Origin Adolescents' Achievement. AB - OBJECTIVES: Immigrant adolescents' academic achievement is crucial to our future economic stability, and Mexican-origin linguistic minority youth in U.S. schools generally demonstrate lower levels of achievement. English as a Second Language (ESL) programs provide an institutional response to these students' needs, the effect of which may vary by the proportion of immigrant students in the school. MEASURES: Using propensity score matching and data from the Adolescent Health and Academic Achievement Study (AHAA) and the National Longitudinal Study of Adolescent Health (Add Health), we estimate the effect of ESL placement on Mexican-origin achievement for first-, second-, and third-generation adolescents separately in schools with many and few immigrant students. RESULTS: The estimated effect of ESL placement varies by both immigrant concentration in the school and by students' generational status. CONCLUSIONS: We find that ESL enrollment may be protective for second-generation Mexican-origin adolescents in high immigrant concentration schools, and may prove detrimental for first generation adolescents in contexts with few other immigrant students. PMID- 20354571 TI - Temperament-Based Intervention: Re-examining Goodness of Fit. AB - The purpose of this paper is to discuss how recent advances in the temperament field have contributed to the scientific foundation of temperament-based intervention. A presentation of the historical origins of temperament-based intervention is followed by examples of recent studies that add to its empirical support. Guidelines for developing and adapting temperament-based interventions are offered. The goodness of fit model, frequently used as a basis for temperament-based intervention, is re-examined through the lens of self regulation. PMID- 20354572 TI - The Use of Female Commercial Sex Workers' Services by Latino Day Laborers. AB - This article reports the characteristics of Latino day laborers who have sex with female commercial sex workers (CSWs). A sample of 450 day laborers in Los Angeles was utilized. Multivariate logistic regression was used to determine the association of independent variables with the likelihood of having sex with a CSW. Overall, 26% of the 450 day laborers reported having had sex with a CSW in the previous 12 months. A lower likelihood of having sex with a CSW was found for those with more than six years of education and for those who were married and living with their spouses. A higher likelihood of having sex with a CSW was found for those who met the criteria for harmful drinking or drug dependence. Commercial sex work has been associated with sexually transmitted infections and other problems among clients of CSWs and warrants further attention by providers working with day laborers. PMID- 20354573 TI - Academic Failure in Secondary School: The Inter-Related Role of Health Problems and Educational Context. AB - This study explores whether the interplay of health problems and school environment predicts academic failure, an individual event with consequences for the life course, as well as for society at large. This exploration proceeds in three steps: 1) we examine whether physical and mental health problems are an academic risk factor during secondary school; 2) we investigate the academic mechanisms underlying this risk status; and 3) we explore whether this risk status varies by school context. A series of logistic regressions reveals that self-rated health and emotional distress are both associated with greater likelihood of failing one or more classes in the next year and that absenteeism, trouble with homework, and student-teacher bonding account for much of these associations. Associations of physical and mental health problems with academic failure vary only slightly across schools, however. We discuss the implications of these findings for both research and policy and argue that the examination of overlap among different domains of adolescent functioning can advance the sociological understanding of health, education, and social problems in general. PMID- 20354574 TI - Results of a Randomized Clinical Trial of the Action of Several Doses of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy. AB - PURPOSE: The purpose of this Phase II randomized-controlled trial was to evaluate the safety and effect of administering several doses of lycopene to men with clinically localized prostate cancer, on intermediate endpoint biomarkers implicated in prostate carcinogenesis. METHODS: Forty-five eligible men with clinically localized prostate cancer were supplemented with 15, 30 or 45 mg of lycopene or no supplement from biopsy to prostatectomy. Compliance to study agent, toxicity, changes in plasma lycopene, serum steroid hormones, PSA and tissue Ki-67 were analyzed from baseline to completion of intervention. RESULTS: Forty-two of forty-five five subjects completed the intervention for approximately 30 days from the time of biopsy until prostatectomy. Plasma lycopene increased from baseline to post treatment in all treatment groups with greatest increase observed in the 45 mg lycopene-supplemented arm compared to the control arm without producing any toxicity. Overall, subjects with prostate cancer had lower baseline levels of plasma lycopene similar to those observed in previous studies in men with prostate cancer. Serum free testosterone decreased with 30 mg lycopene supplementation and total estradiol increased significantly with 30 mg and 45 mg supplementation from baseline to end of treatment, with no significant increases in serum PSA or tissue Ki-67. These changes were not significant compared to the control arm for this sample size and duration of intervention. CONCLUSIONS: Although antioxidant properties of lycopene have been hypothesized to be primarily responsible for its beneficial effects, our study suggests that other mechanisms mediated by steroid hormones may also be involved. PMID- 20354575 TI - A System for Open-Access He Human Lung Imaging at Very Low Field. AB - We describe a prototype system built to allow open-access very-low-field MRI of human lungs using laser-polarized (3)He gas. The system employs an open four-coil electromagnet with an operational B(0) field of 4 mT, and planar gradient coils that generate gradient fields up to 0.18 G/cm in the x and y direction and 0.41 G/cm in the z direction. This system was used to obtain (1)H and (3)He phantom images and supine and upright (3)He images of human lungs. We include discussion on challenges unique to imaging at 50 -200 kHz, including noise filtering and compensation for narrow-bandwidth coils. PMID- 20354576 TI - Numerical Investigation of Coil Configurations That Provide Ultra-High Packing Density of Saccular Aneurysms. AB - BACKGROUND: The long-term outcome of endovascular coiling of cerebral aneurysms is directly related to the packing density at time of treatment. In general, the highest packing density achievable is only about 45% due to the quasi-random distribution of currently available coils within aneurysms. We investigated whether packing densities could be maximized via more ordered coil configurations. METHODS: Three different coil configurations - circular loops, planar spirals, and spherical helices - were investigated. The packing densities achievable in maximally filling the volume of an exemplar human basilar aneurysm with each coil configuration were calculated numerically. Coil packing simulations were also carried out for aneurysms idealized as spheres over diameters ranging from 2 to 30 mm. RESULTS: The packing densities with the loop, spiral, and spherical helix configurations were 82%, 60%, and 73%, respectively, for the human aneurysm model; the numbers of coils required were 693, 34, and 13, respectively. Simulations within idealized aneurysms suggest that aneurysms cannot be packed to more than 91% with coils of constant circular cross-section. The spherical helix configuration provides a constant packing density (coefficient of variation 0.4%) over the range of aneurysm diameters studied as compared to the two other configurations (coefficients of variation 9% and 8%). CONCLUSIONS: Coil configurations that allow for ordered filling of cerebral aneurysms can potentially provide packing densities that are twice those currently achieved. The spherical helix configuration seems to be the most technically feasible and stable configuration of the three coil types investigated. PMID- 20354577 TI - Effect of Representational Distance between Meanings on Recognition of Ambiguous Spoken Words. AB - Previous research indicates that mental representations of word meanings are distributed along both semantic and syntactic dimensions such that nouns and verbs are relatively distinct from one another. Two experiments examined the effect of representational distance between meanings on recognition of ambiguous spoken words by comparing recognition of unambiguous words, noun-verb homonyms, and noun-noun homonyms. In Experiment 1, auditory lexical decision was fastest for unambiguous words, slower for noun-verb homonyms, and slowest for noun-noun homonyms. In Experiment 2, response times for matching spoken words to pictures followed the same pattern and eye fixation time courses revealed converging, gradual time course differences between conditions. These results indicate greater competition between meanings of ambiguous words when the meanings are from the same grammatical class (noun-noun homonyms) than they when are from different grammatical classes (noun-verb homonyms). PMID- 20354578 TI - Hierarchies of Synergies in Human Movements. AB - This brief review addresses the problem of motor redundancy, which exists at many levels of the neuromotor hierarchies involved in the production of voluntary movements. An approach to this problem is described based on the principle of abundance. This approach offers an operational definition for motor synergies using the framework of the uncontrolled manifold hypothesis. It is shown that hierarchical systems have inherent trade-offs between synergies at different control levels. These trade-offs have been demonstrated in experimental studies of human multi-finger pressing and prehension. They are likely to be present in other hierarchical systems, for example those involved in the control of large groups of muscles. The framework of the equilibrium-point hypothesis offers a physiologically based mechanism, which may form the basis for hierarchies of synergies. PMID- 20354579 TI - Identifying positions from affiliation networks: Preserving the duality of people and events. AB - Frank's [Frank, K.A., 1995. Identifying cohesive subgroups. Social Networks 17, 27-56] clustering technique for one-mode social network data is adapted to identify positions in affiliation networks by drawing on recent extensions of p(*) models to two-mode data. The algorithm is applied to the classic Deep South data on southern women and the social events in which they participated with results comparable to other algorithms. Monte Carlo simulations are used to generate sampling distributions to test for the presence of clustering in new data sets and to evaluate the performance of the algorithm. The algorithm and simulation results are then applied to high school students' transcripts from one school from the Adolescent Health and Academic Achievement (AHAA) extension of the National Longitudinal Study of Adolescent Health. PMID- 20354582 TI - Lithium-Ion-Conducting Electrolytes: From an Ionic Liquid to the Polymer Membrane. AB - This work concerns the design, the synthesis, and the characterization of the N butyl-N-ethylpiperidinium N,N-bis(trifluoromethane)sulfonimide (PP(24)TFSI) ionic liquid (IL). To impart Li-ion transport, a suitable amount of lithium N,N-bis (trifluoromethane)sulfonimide (LiTFSI) is added to the IL. The Li-IL mixture displays ionic conductivity values on the order of 10(-4) S cm(-1) and an electrochemical stability window in the range of 1.8-4.5 V vs Li(+)/Li. The voltammetric analysis demonstrates that the cathodic decomposition gives rise to a passivating layer on the surface of the working electrode, which kinetically extends the stability of the Li/IL interface as confirmed by electrochemical impedance spectroscopy measurements. The LiTFSI-PP(24)TFSI mixture is incorporated in a poly(vinylidene fluoride-co-hexafluoropropylene) matrix to form various electrolyte membranes with different LiTFSI-PP(24)TFSI contents. The ionic conductivity of all the membranes resembles that of the LiTFSI-IL mixture, suggesting an ionic transport mechanism similar to that of the liquid component. NMR measurements demonstrate a reduction in the mobility of all ions following the addition of LiTFSI to the PP(24)TFSI IL and when incorporating the mixture into the membrane. Finally, an unexpected but potentially significant enhancement in Li transference number is observed in passing from the liquid to the membrane electrolyte system. PMID- 20354581 TI - Psychometric Properties of a Revised Form of the Drug-Taking Confidence Questionnaire for Use with Adolescents. AB - Self-efficacy is an important cognitive predictor of substance abuse treatment outcome. While measures of coping self-efficacy are related to substance use relapse in adults, their properties are not well known in adolescent populations. The present study examined 223 adolescents while in treatment for substance abuse and comorbid psychiatric disorders. Responses on the Drug-Taking Confidence Questionnaire (DTCQ; Sklar et al., 1997) were used to construct a 37-item, 5 factor version for use with adolescents. Exploratory and confirmatory factor analysis identified the following factors: 1) Negative Situations, 2) Social/Drugs, 3) Pleasant Emotions, 4) Testing Personal Control, and 5) Physical/Intimate. Data preliminarily support the construct, concurrent, and predictive validity of the revised instrument. PMID- 20354584 TI - Unexpected Incorporation of Bromine at a Non-anomeric Position during the Synthesis of an O-Glycosylated Diazeniumdiolate. PMID- 20354580 TI - Long-chain acyl-CoA synthetases and fatty acid channeling. AB - Thirteen homologous proteins comprise the long-chain acyl-CoA synthetase (ACSL), fatty acid transport protein (FATP), and bubblegum (ACSBG) subfamilies that activate long-chain and very-long-chain fatty acids to form acyl-CoAs. Gain- and loss-of-function studies show marked differences in the ability of these enzymes to channel fatty acids into different pathways of complex lipid synthesis. Further, the ability of the ACSLs and FATPs to enhance cellular FA uptake does not always require these proteins to be present on the plasma membrane; instead, FA uptake can be increased by enhancing its conversion to acyl-CoA and its metabolism in downstream pathways. Since altered fatty acid metabolism is a hallmark of numerous metabolic diseases and pathological conditions, the ACSL, FATP and ACSBG isoforms are likely to play important roles in disease etiology. PMID- 20354583 TI - Free energy and kinetics of conformational transitions from Voronoi tessellated milestoning with restraining potentials. AB - Milestoning is a method aimed at reconstructing the statistical properties of the long-time dynamics of a system by exploiting the crossing statistics of a set of hypersurfaces, called the "milestones", placed along the reaction coordinate [Faradjian and Elber, J. Chem. Phys.2004, 120, 10880]. Recently, Vanden-Eijnden and Venturoli [J. Chem. Phys.2009, 130, 194101] showed that when a complete Voronoi tessellation of the configurational space is available, milestoning can be reformulated to utilise the statistics from a series of independent simulations, each confined within a single cell via strict reflections at the boundaries. As a byproduct, this "Voronoi tessellated milestoning" method also permits to compute the free energy of the tessellation. Here, the method is extended to support the usage of differentiable restraining potentials to confine the trajectories within each cell. PMID- 20354585 TI - Stimulated Raman scattering: old physics, new applications. AB - Stimulated Raman scattering as a promising way of expanding the tunability of ultrafast lasers and as an exciting new biomedical imaging modality capable of selective excitation and chemically-specific diagnostics of molecular species. PMID- 20354586 TI - Effect of surface phosphorus functionalities of activated carbons containing oxygen and nitrogen on electrochemical capacitance. AB - Micro/mesoporous activated carbons containing oxygen and phosphorus heteroatoms were modified by incorporation of nitrogen using melamine and urea precursors. The surface chemistry was analyzed by the means of elemental analysis, XPS, and (31)P MAS NMR. The results indicate that upon the incorporation of nitrogen at high temperatures not only new species involving carbon/nitrogen/oxygen are formed but also the phosphorous environment is significantly altered. Both urea and melamine precursors have similar effects on formation of P-N and P-C bonds. These compounds, although present in small but measurable quantities seem to affect the performance of carbons in electrochemical capacitors. With an increase in the heterogeneity of phosphorus containing species and with a decrease in the content pyrophosphates the capacitance increases and the retention ratio of the capacitor is improved. PMID- 20354587 TI - Li Ion Conducting Polymer Gel Electrolytes Based on Ionic Liquid/PVDF-HFP Blends. AB - Ionic liquids thermodynamically compatible with Li metal are very promising for applications to rechargeable lithium batteries. 1-methyl-3-propylpyrrolidinium bis(trifluoromethanesulfonyl)imide (P(13)TFSI) is screened out as a particularly promising ionic liquid in this study. Dimensionally stable, elastic, flexible, nonvolatile polymer gel electrolytes (PGEs) with high electrochemical stabilities, high ionic conductivities and other desirable properties have been synthesized by dissolving Li imide salt (LiTFSI) in P(13)TFSI ionic liquid and then mixing the electrolyte solution with poly(vinylidene-co-hexafluoropropylene) (PVDF-HFP) copolymer. Adding small amounts of ethylene carbonate to the polymer gel electrolytes dramatically improves the ionic conductivity, net Li ion transport concentration, and Li ion transport kinetics of these electrolytes. They are thus favorable and offer good prospects in the application to rechargeable Li batteries including open systems like Li/air batteries, as well as more "conventional" rechargeable lithium and lithium ion batteries. PMID- 20354588 TI - Discovery and design of DNA and RNA ligase inhibitors in infectious microorganisms. AB - BACKGROUND: Members of the nucleotidyltransferase superfamily known as DNA and RNA ligases carry out the enzymatic process of polynucleotide ligation. These guardians of genomic integrity share a three-step ligation mechanism, as well as common core structural elements. Both DNA and RNA ligases have experienced a surge of recent interest as chemotherapeutic targets for the treatment of a range of diseases, including bacterial infection, cancer, and the diseases caused by the protozoan parasites known as trypanosomes. OBJECTIVE: In this review, we will focus on efforts targeting pathogenic microorganisms; specifically, bacterial NAD(+)-dependent DNA ligases, which are promising broad-spectrum antibiotic targets, and ATP-dependent RNA editing ligases from Trypanosoma brucei, the species responsible for the devastating neurodegenerative disease, African sleeping sickness. CONCLUSION: High quality crystal structures of both NAD(+) dependent DNA ligase and the Trypanosoma brucei RNA editing ligase have facilitated the development of a number of promising leads. For both targets, further progress will require surmounting permeability issues and improving selectivity and affinity. PMID- 20354589 TI - Ethnic Differences in Suicidal Ideation and Attempts. AB - Suicide is one of the leading causes of death, and suicidal ideation and attempts are a major public health problem. However, little is known about the relationship between ethnicity and suicidal behaviors.The goal of this article is to provide an update on the relationship between ethnicity and suicidal ideation and attempts. We review the rates of suicide ideation/attempts across ethnic groups in the US, and the risk factors associated with suicide attempts in each ethnic group.The results of published studies have been inconsistent. Some studies have suggested that non-Hispanic Whites have significantly higher suicide attempt risk than other ethnic groups, while two studies using national data did not find any significant relationship between race/ethnicity and suicide ideation or attempts. From the epidemiological point of view, these findings underscore the need to conduct large studies in general population samples that include enough individuals from all ethnic groups and that are large enough to detect significant effects among those groups. From the clinical point of view, mental health professionals should focus on factors that have been consistently found to be strongly associated with suicide attempts across different populations, including major depression and other psychiatric disorders, female gender, and young age. PMID- 20354590 TI - Land use change: complexity and comparisons. PMID- 20354591 TI - Analysis of Multiple Manding Topographies during Functional Communication Training. AB - We evaluated the effects of reinforcing multiple manding topographies during functional communication training (FCT) to decrease problem behavior for three preschool-age children. During Phase 1, a functional analysis identified conditions that maintained problem behavior for each child. During Phase 2, the children's parents taught them to request positive reinforcers (attention or toys) via vocal manding, manual signing, or touching a picture/word card with or without a microswitch recording device. A non-concurrent multiple-baseline design across children was used to evaluate FCT outcomes. Results showed that problem behavior decreased for all three children. Results also indicated that the children initially used multiple manding topographies but displayed a preference for vocal manding over time. PMID- 20354592 TI - Behavioral Health in Developmental Disabilities: A Comprehensive Program of Nutrition, Exercise, and Weight Reduction. AB - We review the literature on the prevalence and conditions resulting in overweight and obesity in people with intellectual disability (ID), followed by obesity treatment research with typically developing children and adaptations for children with ID. In addition to proposing directions for future research and practice, we report a comprehensive randomized control trial (RCT) of family based behavioral intervention targeting weight loss among adolescents with Down syndrome. PMID- 20354594 TI - A Semiparametric Regression Cure Model for Interval-Censored Data. AB - Motivated by medical studies in which patients could be cured of disease but the disease event time may be subject to interval censoring, we presents a semiparametric non-mixture cure model for the regression analysis of interval censored time-to-event datxa. We develop semiparametric maximum likelihood estimation for the model using the expectation-maximization method for interval censored data. The maximization step for the baseline function is nonparametric and numerically challenging. We develop an efficient and numerically stable algorithm via modern convex optimization techniques, yielding a self-consistency algorithm for the maximization step. We prove the strong consistency of the maximum likelihood estimators under the Hellinger distance, which is an appropriate metric for the asymptotic property of the estimators for interval censored data. We assess the performance of the estimators in a simulation study with small to moderate sample sizes. To illustrate the method, we also analyze a real data set from a medical study for the biochemical recurrence of prostate cancer among patients who have undergone radical prostatectomy. Supplemental materials for the computational algorithm are available online. PMID- 20354595 TI - An integrated model for enzyme catalysis emerges from studies of hydrogen tunneling. AB - The origins of the enormous rate accelerations brought about by enzymes are discussed. The focus is on enzymatic C-H activation, which has been shown to take place via tunneling. Four enzyme systems illustrate the impact of site-specific mutagenesis, changes in temperature or changes in protein solvation on the tunneling properties. A model emerges in which conformational sampling is required to access a subset of protein conformers where the H-donor and acceptor undergo a close approach. The evidence for an inverse relationship between protein flexibility and active site compression is likely to extend to all classes of enzyme catalysts. PMID- 20354596 TI - Barycentric extension of generalized matching. AB - In most studies of choice under concurrent schedules of reinforcement, two physically identical operanda are provided. In the "real world," however, more than two choice alternatives are often available and biases are common. This paper describes a method for studying choices among an indefinite number of alternatives when large biases are present. Twenty rats were rewarded for choosing among five operanda with reinforcers scheduled probabilistically and concurrently. Large biases were generated by differences among the operanda: two were levers and three were pigeon keys. The results showed that when reinforcer frequencies were systematically varied, an extension of Baum's (1974) Generalized Matching Model, referred to as the Barycentric Matching Model, provided an excellent description of the data, including individual bias values for each of the operanda and a single exponent indicating sensitivity to reinforcer ratios. PMID- 20354593 TI - HIV-1 Transmission, Replication Fitness and Disease Progression. AB - Upon transmission, human immunodeficiency virus type 1 (HIV-1) establishes infection of the lymphatic reservoir, leading to profound depletion of the memory CD4(+) T cell population, despite the induction of the adaptive immune response. The rapid evolution and association of viral variants having distinct characteristics with different stages of infection, the level of viral burden, and rate of disease progression suggest a role for viral variants in this process. Here, we review the literature on HIV-1 variants and disease and discuss the importance of viral fitness for transmission and disease. PMID- 20354597 TI - Quantification of ethanol's antipunishment effect in humans using the generalized matching equation. AB - Increases in rates of punished behavior by the administration of anxiolytic drugs (called antipunishment effects) are well established in animals but not humans. The present study examined antipunishment effects of ethanol in humans using a choice procedure. The behavior of 5 participants was placed under six concurrent variable-interval schedules of monetary reinforcement. In three of the six concurrent schedules, punishment, in the form of monetary loss, was superimposed on one alternative. Data were analyzed according to the generalized matching equation which distinguishes between bias (allocation of behavior beyond what matching to relative reinforcer densities would predict) and sensitivity to reinforcement (how well behavior tracks relative reinforcer densities). In addition, participants completed a pencil-tapping test. Under placebo punishment conditions, all participants demonstrated low response rates and a bias against the alternative associated with punishment, despite a resultant loss of available reinforcers. Bias against the punished alternative was dose-dependently reduced in participants shown to be most sensitive to ethanol (0.6, 1.2, and 1.8 g/kg) in measures of overall responding and on the pencil-tapping test. No ethanol-induced change in bias was noted when punishment was not imposed. Sensitivity to reinforcement also decreased for participants shown to be sensitive to ethanol. In addition to extending antipunishment effects to humans, these results also show that antipunishment effects can be quantified via the matching equation. PMID- 20354598 TI - The effect of changes in criterion value on differential reinforcement of low rate schedule performance. AB - The differential reinforcement of low rate (DRL) schedule is commonly used to assess impulsivity, hyperactivity, and the cognitive effects of pharmacological treatments on performance. A DRL schedule requires subjects to wait a certain minimum amount of time between successive responses to receive reinforcement. The DRL criterion value, which specifies the minimum wait time between responses, is often shifted towards increasingly longer values over the course of training. However, the process invoked by shifting DRL values is poorly understood. Experiment 1 compared performance on a DRL 30-s schedule versus a DRL 15-s schedule that was later shifted to a DRL 30-s schedule. Dependent measures assessing interresponse time (IRT) production and reward-earning efficiency showed significant detrimental effects following a DRL schedule transition in comparison with the performance on a maintained DRL 30-s schedule. Experiments 2a and 2b assessed the effects of small incremental changes vs. a sudden large shift in the DRL criterion on performance. The incremental changes produced little to no disruption in performance compared to a sudden large shift. The results indicate that the common practice of incrementing the DRL criterion over sessions may be an inefficient means of training stable DRL performance. PMID- 20354599 TI - Resistance to change and frequency of response-dependent stimuli uncorrelated with reinforcement. AB - Stimuli uncorrelated with reinforcement have been shown to enhance response rates and resistance to disruption; however, the effects of different rates of stimulus presentations have not been assessed. In two experiments, we assessed the effects of adding different rates of response-dependent brief stimuli uncorrelated with primary reinforcement on relative response rates and resistance to change. In both experiments, pigeons responded on variable-interval 60-s schedules of food reinforcement in two components of a multiple schedule, and brief response dependent keylight-color changes were added to one or both components. Although relative response rates were not systematically affected in either experiment, relative resistance to presession feeding and extinction were. In Experiment 1, adding stimuli on a variable-interval schedule to one component of a multiple schedule either at a low rate (1 per min) for one group or at a high rate (4 per min) for another group similarly increased resistance to disruption in the components with added stimuli. When high and low rates of stimuli were presented across components (i.e., within subjects) in Experiment 2, however, relative resistance to disruption was greater in the component presenting stimuli at a lower rate. These results suggest that stimuli uncorrelated with food reinforcement do not strengthen responding in the same way as primary reinforcers. PMID- 20354600 TI - Observing responses and serial stimuli: searching for the reinforcing properties of the S-. AB - The control exerted by a stimulus associated with an extinction component (S-) on observing responses was determined as a function of its temporal relation with the onset of the reinforcement component. Lever pressing by rats was reinforced on a mixed random-interval extinction schedule. Each press on a second lever produced stimuli associated with the component of the schedule in effect. In Experiment 1 a response-dependent clock procedure that incorporated different stimuli associated with an extinction component of a variable duration was used. When a single S- was presented throughout the extinction component, the rate of observing remained relatively constant across this component. In the response dependent clock procedure, observing responses increased from the beginning to the end of the extinction component. This result was replicated in Experiment 2, using a similar clock procedure but keeping the number of stimuli per extinction component constant. We conclude that the S- can function as a conditioned reinforcer, a neutral stimulus or as an aversive stimulus, depending on its temporal location within the extinction component. PMID- 20354601 TI - Emergent conditional relations in a Go/No-Go procedure: figure-ground and stimulus-position compound relations. AB - Past research has demonstrated emergent conditional relations using a go/no-go procedure with pairs of figures displayed side-by-side on a computer screen. The present study sought to extend applications of this procedure. In Experiment 1, we evaluated whether emergent conditional relations could be demonstrated when two-component stimuli were displayed in figure-ground relationships-abstract figures displayed on backgrounds of different colors. Five normally capable adults participated. During training, each two-component stimulus was presented successively. Responses emitted in the presence of some stimulus pairs (A1B1, A2B2, A3B3, B1C1, B2C2 and B3C3) were reinforced, whereas responses emitted in the presence of other pairs (A1B2, A1B3, A2B1, A2B3, A3B1, A3B2, B1C2, B1C3, B2C1, B2C3, B3C1 and B3C2) were not. During tests, new configurations (AC and CA) were presented, thus emulating structurally the matching-to-sample tests employed in typical equivalence studies. All participants showed emergent relations consistent with stimulus equivalence during testing. In Experiment 2, we systematically replicated the procedures with stimulus compounds consisting of four figures (A1, A2, C1 and C2) and two locations (left - B1 and right - B2). All 6 normally capable adults exhibited emergent stimulus-stimulus relations. Together, these experiments show that the go/no-go procedure is a potentially useful alternative for studying emergent conditional relations when matching-to sample is procedurally cumbersome or impossible to use. PMID- 20354602 TI - Electrophysiological correlates of stimulus equivalence processes. AB - Research reported here concerns neural processes relating to stimulus equivalence class formation. In Experiment 1, two types of word pairs were presented successively to normally capable adults. In one type, the words had related usage in English (e.g., uncle, aunt). In the other, the two words were not typically related in their usage (e.g., wrist, corn). For pairs of both types, event related cortical potentials were recorded during and immediately after the presentation of the second word. The obtained waveforms differentiated these two types of pairs. For the unrelated pairs, the waveforms were significantly more negative about 400 ms after the second word was presented, thus replicating the "N400" phenomenon of the cognitive neuroscience literature. In addition, there was a strong positive-tending wave form difference post-stimulus presentation (peaked at about 500 ms) that also differentiated the unrelated from related stimulus pairs. In Experiment 2, the procedures were extended to study arbitrary stimulus-stimulus relations established via matching-to-sample training. Participants were experimentally naive adults. Sample stimuli (Set A) were trigrams, and comparison stimuli (Sets B, C, D, E, and F) were nonrepresentative forms. Behavioral tests evaluated potentially emergent equivalence relations (i.e., BD, DF, CE, etc.). All participants exhibited classes consistent with the arbitrary matching training. They were also exposed also to an event-related potential procedure like that used in Experiment 1. Some received the ERP procedure before equivalence tests and some after. Only those participants who received ERP procedures after equivalence tests exhibited robust N400 differentiation initially. The positivity observed in Experiment 1 was absent for all participants. These results support speculations that equivalence tests may provide contextual support for the formation of equivalence classes including those that emerge gradually during testing. PMID- 20354603 TI - Effects of differing response-force requirements on food-maintained responding in C57Bl/6J mice. AB - The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all responses) that exceeded the requirement and produced a reinforcer. The reinforcer was sweetened, condensed milk, delivered upon response termination. All mice were exposed to two ascending series of criterion force requirements (2, 4, 8, 16, and 32 g). Increasing the force requirement initially decreased criterion response rates, but criterion response rates recovered with continued exposure, except at the 32-g requirement. Response rates for all measured responses initially increased with increasing force requirements, but then decreased with continued exposure. The second exposure series produced more stable response rate changes than the first series. The time-integral of force (area under the force-time curve for individual responses, which is proportional to energy expenditure for each response) increased with the increase in the force requirement. The C57BL/6J inbred strain generated average force output similar to CD-1 outbred stock mice trained on the same force requirements. C57BL/6J inbred strain mice differed from CD-1 mice in initial response rates (for all responses above threshold) and had lower response rates at the 16 and 32 g requirements resulting in lower total force output. These data show for both mice types that increased force requirements resulted in increased overall responding (all measured responses), which contradicts a punishment interpretation of criterion response decrements. C57BL?6 inbred mice showed individual differences comparable to the outbred CD-1 stock. C57BL/6 mice did not maintain responding as well at the higher force requirements, which may be due to their small body size and weight, compared to the larger and heavier CD 1 mice. PMID- 20354607 TI - An alcoholysis route to a Cu16 cluster, and the influence of the alcohol. AB - A systematic investigation of the alcoholysis of copper(II) pivalate (piv(-)) solutions has led to a series of Cu(2), Cu(6), and Cu(16) products, depending on the alcohol used as solvent. When Pr(n)OH or Bu(n)OH was employed, the products were the clusters [Cu(16)O(4)(OH)(4)(OR)(8)(piv)(12)(ROH)] (R = Pr(n), Bu(n)) that are almost isostructural. The Cu(16) clusters are antiferromagnetically coupled with an S = 0 spin ground state. PMID- 20354604 TI - Behavior analysis and ecological psychology: past, present, and future. a review of Harry Heft's Ecological Psychology in context. AB - Relations between behavior analysis and ecological psychology have been strained for years, notwithstanding the occasional comment on their affinities. Harry Heft's (2001)Ecological Psychology in Context provides an occasion for reviewing anew those relations and affinities. It describes the genesis of ecological psychology in James's radical empiricism; addresses Holt's neorealism and Gestalt psychology; and synthesizes Gibson's ecological psychology and Barker's ecobehavioral science as a means for understanding everyday human behavior. Although behavior analysis is excluded from this account, Heft's book warrants a review nonetheless: It describes ecological psychology in ways that are congruent and complementary with behavior analysis (e.g., nonmediational theorizing; the provinces of natural history and natural science). After introducing modern ecological psychology, I comment on (a) Heft's admirable, albeit selective, historiography; (b) his ecological psychology-past and present-as it relates to Skinner's science and system (e.g., affordances, molar behavior); (c) his misunderstandings of Skinner's behaviorism (e.g., reductionistic, mechanistic, molecular); and (d) the theoretical status of Heft's cognitive terms and talk (i.e., in ontology, epistemology, syntax). I conclude by considering the alliance and integration of ecological psychology and behavior analysis, and their implications for unifying and transforming psychology as a life science, albeit more for the future than at present. PMID- 20354608 TI - Amine templated two- and three-dimensional uranyl sulfates. AB - Structural variability in amine template uranyl sulfate frameworks is observed with two- and three-dimensional structures containing channels of dimensions 7.4 A x 5.1 A, 36 A x 5.8 A, and 10 A x 10 A. PMID- 20354609 TI - A lanthanide binding peptide with short chelating side-chains: structural impact of the backbone coordination. AB - A lanthanide-binding hexapeptide containing two short aminodiacetate side-chains favours the coordination of a backbone carbonyl, which determines the secondary structure of the complex and illustrates the interplay between complex formation and secondary peptide structures. PMID- 20354610 TI - Wheel-like Mn(II)6 and Ni(II)6 complexes from the use of 2-pyridinealdoxime and carboxylates. AB - The employment of 2-pyridinealdoxime, (py)C(H)NOH, in nickel(II) and manganese(II) carboxylate chemistry under solvothermal conditions is reported. The syntheses, crystal structures and magnetochemical characterization (for two representative compounds) are described for [Ni(6)(O(2)CMe)(6){(py)C(H)NO}(6)].H(2)O (1.H(2)O), [Ni(6)(O(2)CPh)(6){(py)C(H)NO}(6)].2EtOH (2.2EtOH), [Ni(6){(4 Cl)O(2)CPh}(6){(py)C(H)NO}(6)].2EtOH (3.2EtOH) and [Mn(6)(O(2)CMe)(6){(py)C(H)NO}(6)].H(2)O (4.H(2)O), where (4-Cl)PhCO(2)(-) is 4 chlorobenzoate. The reactions of M(O(2)CMe)(2).4H(2)O (M = Ni, Mn) with one equivalent of (py)C(H)NOH in EtOH at 120 degrees C under autogenous pressure give isostructural 1.H(2)O and 4.H(2)O. Complexes 2.2EtOH and 3.2EtOH were obtained from the 1 : 1 : 1 Ni(O(2)CMe)(2).4H(2)O/{(py)C(H)NOH/(X)PhCO(2)H reaction mixtures in EtOH under solvothermal conditions (X = H, 4-Cl). The structurally similar clusters 1-4 have a wheel-like topology with the six metal ions in a chair conformation. Each metal site is bound to four oxygen and two nitrogen atoms; the donor atoms come from two carboxylate oxygens, two oximate oxygens, one pyridyl nitrogen and one oximate nitrogen atom. The carboxylate ligands show the syn, syn eta(1):eta(1):mu mode, while the (py)C(H)NO(-) ions behave as eta(1):eta(1):eta(2):mu(3) ligands. Each metal...metal vector is bridged by one carboxylate group, one mu-O derived from a (py)C(H)NO(-) ligand and by one diatomic oximate-NO- group from an adjacent (py)C(H)NO(-) group. The IR spectra of the complexes are discussed in terms of the coordination modes of the ligands. Variable-temperature, solid-state dc magnetic susceptibility studies were carried out on polycrystalline samples of 1 and 4. The data in the 2.0-300 K range have been fit to a model with one J value revealing moderate (1) or weak (2) antiferromagnetic M(II)...M(II) exchange interactions. This work demonstrates the synthetic potential of combining (py)C(H)NOH with carboxylate ligands and the usefulness of solvothermal techniques in 3d-metal cluster chemistry. PMID- 20354611 TI - A thiosemicarbazone ligand functionalized by a phosphine group: reactivity toward coinage metal ions. AB - The reactivity of the phosphino-thiosemicarbazone ligand 2-(2 (diphenylphosphino)benzylidene)-N-ethylthiosemicarbazone (HLPEt) toward M(I) halides (M = Cu, Ag, Au) was studied. The complexes obtained, with formulae [Cu(HLPEt)(2)]Br (1), [Cu(HLPEt)(2)]I.2H(2)O (2), [Ag(HLPEt)(LPEt)].3H(2)O (3), [Au(2)(HLPEt)(2)Cl]Cl.CH(3)OH (4) were satisfactorily characterized by elemental analysis, IR, ESI and (1)H/(31)P NMR. Moreover, we have obtained the crystal structure of the ligand HLPEt and its sulfide oxidized form HLP(S)Et, which represents a new case of desulfurization process in thiosemicarbazone ligands. In addition, we present the crystal structure of the complexes 1 + H(2)O + 3MeOH and [Au(2)(HLPEt)(4)Cl]Cl.3CH(3)OH (5), together with their interesting crystal packing. The complex 5 is an interesting case of a pseudo-chloronium gold(I) complex. The ligand HLPEt and the complexes 3 and 4 display intense luminescence at room temperature. PMID- 20354612 TI - Sticky complexes: carboxylic acid-functionalized N-phenylpyridin-2-ylmethanimine ligands as anchoring domains for copper and ruthenium dye-sensitized solar cells. AB - Four members of a series of N-phenylpyridin-2-ylmethanimine ligands (L) decorated with carboxylic acid functionalities have been prepared. The ligand design allows a copper(i) complex [CuL(2)](+) to bind to a TiO(2) surface through the simultaneous use of two carboxylate anchoring domains. Complexes of the type [CuL(2)][PF(6)], [CuL(NCMe)(2)][PF(6)] and [Ru(bpy)(2)L][PF(6)](2) have been synthesized and characterized by (1)H and (13)C NMR and electronic absorption spectroscopies, mass spectrometry and, for four of the complexes, single crystal X-ray diffraction. Dye-sensitized solar cells (DSCs) have been fabricated using the new complexes and the performances of the dyes assessed. The copper(I) complexes show good surface coverage and tuning of the electrolyte and the electronic properties of the ligands is now required to enhance the efficiencies of the DSCs. PMID- 20354613 TI - Tuning the reactivity of chelated dinuclear Pt(II) complexes through a flexible diamine linker. A detailed kinetic and mechanistic study. AB - The rate of displacement of the aqua ligands by three neutral nucleophiles (Nu) of different steric demands, namely thiourea (tu), N,N'-dimethylthiourea (dmtu) and N,N,N',N'-tetramethylthiourea (tmtu) and an anionic nucleophile (I(-)) in complexes of the form [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl) N(CH(2))(n)N](CF(3)SO(3))(4), n = 2 (En); 3 (Prop); 4 (But); 6 (Hex); 8 (Oct) and 10 (Dec), was studied under pseudo first-order conditions as a function of concentration, temperature and pressure using stopped-flow techniques and UV visible spectrophotometry. The pseudo first-order rate constants, k(obs(1(st)/2(nd))), for the simultaneous substitution of the aqua ligands and the proposed subsequent dechelation of the pyridyl units, respectively, agreed well to the rate law: k(obs(1(st)/2(nd))) = k(2(1(st)/2(nd)))[Nu]. High negative activation entropies, negative volumes of activation and second-order kinetics for the displacement reactions all support an associative mode of activation. Except for Prop, the rate of the simultaneous substitution of the aqua ligands in the complexes was found to increase as the chain length of the linker increases from En to Hex, beyond which any further increase in chain length is not accompanied by a further increase in reactivity. The reactivity trend of the even bridged complexes with C(2h) symmetry is ascribed to a concomitant decrease in axial steric influences imposed on one side of the square-planar picolyl chelates by the other as the chain length increases. Based on the model structures of the complexes, this kind of steric imposition occurs only in complexes with an even number of CH(2) groups within the linker. The Prop complex, having a C(2v) symmetry showed exceptional high reactivity towards the nucleophiles. A cage effect, evolving from its bowl-shaped molecular structure, is proposed to explain this high reactivity. The order of reactivity of the nucleophiles increased in the order I(-) >> tu approximately dmtu > tmtu, in line with the strong electrostatic interactions between the highly polarizable iodide nucleophile and the Pt centers, steric retardation effects in the case of tmtu and dominating positive inductive effects for the dmtu nucleophile. PMID- 20354614 TI - Palladium(II) complexes with pentafluorophenyl ligands: structures, C6F5 fluxionality by 2D-NMR studies and pre-catalysts for the vinyl addition polymerization of norbornene. AB - The palladium(II) complex [Pd(C(6)F(5))Cl(bpzm*)] (5) [bpzm* = bis(3,5 dimethylpyrazol-1-yl)methane] was characterized by (1)H,(1)H-TOCSY, (1)H-NOE difference spectra, (1)H,(19)F-HOESY and (13)C,(1)H-HMBC 2D-NMR techniques. Chemical exchange of the methylene protons from (1)H,(1)H-NOESY cross peaks and exchange of the ortho- and meta-fluorine atoms, respectively, from (19)F,(19)F EXSY cross peaks indicates that the Pd-bpzm* chelate ring boat-to-boat inversion occurs at a rate slower than the NMR time scale together with a concomitant change of the C(6)F(5) atom positions. The presence of three (19)F-NMR signals for 2F(o) : 1F(p) : 2F(m) of the C(6)F(5) ligand for complexes [Pd(C(6)F(5))Cl(tmeda)] (1) and [Pd(C(6)F(5))Cl(bipy)] (3) (tmeda = N,N,N',N' tetramethylethylenediamine; bipy = 2,2'-bipyridine) is interpreted as being due to identical hemi-spaces above and below an apparent symmetry plane coinciding with the Pd-coordination plane instead of free ring rotation. The molecular structures of 1, 3 and 5 from single-crystal studies suggest that the hindered C(6)F(5) rotation is not limited to 5 but is also present in 1 and 3 due to ligand repulsion. Complexes [Pd(C(6)F(5))Cl(tmeda)] (1), [Pd(C(6)F(5))OH(tmeda)] (2), [Pd(C(6)F(5))Cl(bipy)] (3), [Pd(C(6)F(5))OH(bipy)] (4) and [Pd(C(6)F(5))Cl(bpzm*)] (5) have been applied as pre-catalysts for the vinyl homopolymerization of norbornene in combination with the cocatalyst methylaluminoxane (MAO). Activities of more than 10(6) g(polymer)/(mol(Pd) h) could be reached with these catalytic systems. Based on the spectrochemical series, pre-catalysts 1 and 2 with the pure sigma-donor and more weakly bound aliphatic amine ligands showed higher polymerization activities than compounds 3 5 with modest pi-accepting and stronger bound aromatic substituents. This is reasoned with a kinetic activation effect through a faster removal of the more weakly bound ligands upon reaction with MAO together with the chloro or hydroxo ligands to give the active, almost "naked" Pd(2+) cations. For the activation mechanism, (1)H-, (13)C- and (19)F-NMR studies of the MAO activated complex 5 showed about 13% chlorine-to-methyl exchange for a molar Pd : Al ratio of 1 : 10. For 5 : MAO at a Pd : Al ratio of 1 : 100 abstraction of C(6)F(5) takes place with a redox reaction giving Pd metal and C(6)F(5)-CH(3) in the absence of norbornene monomer. PMID- 20354615 TI - Bis(thiosemicarbazones) as bifunctional chelators for the room temperature 64 copper labeling of peptides. AB - A range of new carboxylate functionalised bis(thiosemicarbazone) ligands and their Cu(II) complexes have been prepared, fully characterised and radiolabeled in high yield with both (64)Cu and (99m)Tc. Conjugation to a bombesin derivative was achieved using standard solid phase synthetic methodologies and the (64)Cu labeled conjugate was shown to have good tumour uptake in mice with xenografted PC-3 tumours. PMID- 20354616 TI - Synthesis and structures of novel 1-methylcytosinato-bridged (ethylenediamine)platinum(II) and platinum(III) dinuclear complexes. AB - The reaction of [Pt(en)(H(2)O)(2)](2+) with 1 equivalent of 1-methylcytosine at an initial pH of 6 ultimately led to the 1-methylcytosinato-bridged (ethylenediamine)platinum(II) dimer, [(en)Pt(MetCyt-H)(2)Pt(en)](NO(3))(2) (1). The species during the reactions prior to formation of 1 have been investigated by using (195)Pt NMR spectroscopy. From the reaction mixture the [Pt(en)(MetCyt)(2)](NO(3))(2) complex (3) could be isolated and structurally characterized. A rational synthesis of 1 was also achieved by dimerization of [Pt(en)(MetCyt)(H(2)O)](NO(3))(2). According to X-ray structure analysis, the Pt Pt distance of 2.9816(3) A in 1 is well comparable with the corresponding value found in the cis-diammineplatinum(II) analog (2.981(2) A). Oxidation of 1 with K(2)S(2)O(8) led to the symmetrically sulfate-capped diplatinum(III) complex with two ethylenediamine ligands equatorially bound to the two Pt atoms ht [(SO(4))(en)Pt(MeCyt-H)(2)Pt(en)(SO(4))] (5), as established by X-ray crystallography. When the oxidation was carried out in the presence of HClO(4), the formation of the hydroxido/aqua ht-1-methylcytosinato bridged (en)Pt(III) dimer ht-[H(2)O(en)Pt(MetCyt-H)(2)Pt(en)OH](ClO(4))(3) (6) was observed, as supported by elemental and X-ray structure analysis. In the structure of 6, two ethylenediamine ligands are differently bound to the two Pt centers: one of them equatorially while the second one caps the opposite axial site of the diplatinum(III) core. The Pt-Pt distances in the platinum(iii) dimers are 2.5982(4) in 5 and 2.5569(3) A in 6. PMID- 20354617 TI - The effect on the lanthanide luminescence of structurally simple Eu(III) cyclen complexes upon deprotonation of metal bound water molecules and amide based pendant arms. AB - A series of substituted 1,4,7,10-tetraazacylcododecane ligands 1-4, possessing sensitizing nitrobenzene or naphthalene antennae, as one of the amide pendant arms, and their complexes with europium(III) were synthesised. The protonation constants and the metal ion stability constants of two of these ligands were determined by potentiometric titration. The pK(a) of the water molecules coordinated to the complexed metal ion were determined by both luminescent and potentiometric measurements. The luminescence pH dependence of a further three Eu(III) complexes, 5-7, which lack any antennae, were also studied with the aim of gaining a better understanding of the role of the metal bound water molecules in the luminescence properties of such complexes upon direct excitation of the lanthanide ion. The results from these luminescent measurements demonstrate that the Eu(III) emission was significantly modulated as a function of pH for all the complexes, which we assigned to changes occurring in the coordination environment of the ion within the cyclen system, caused by deprotonation of metal bound water molecules and/or deprotonation of pendent amide arms. PMID- 20354618 TI - Synthesis and ethylene trimerisation capability of new chromium(II) and chromium(III) heteroscorpionate complexes. AB - Reaction of (Me(2)pz)(2)CHSiMe(2)N(H)R (R = (i)Pr or Ph) or (Me(2)pz)(2)CHSiMe(2)NMe(2) with CrCl(3)(THF)(3) or CrCl(2)(THF)(2) gave Cr{(Me(2)pz)(2)CHSiMe(2)NR(1)R(2)}Cl(3) (R(1) = H, R(2) = (i)Pr (10) or Ph (11); R(1) = R(2) = Me (15)) or Cr{(Me(2)pz)(2)CHSiMe(2)NR(1)R(2)}Cl(2)(THF) (R(1) = H, R(2) = (i)Pr (12) or Ph (13); R(1) = R(2) = Me (16)), respectively. Compounds 10 and 11 were crystallographically characterized and the magnetic behaviour of all the new compounds was evaluated using SQUID magnetometry. Reaction of CrCl(3)(THF)(3) with Li{C(Me(2)pz)(3)}(THF) gave the zwitterionic complex Cr{C(Me(2)pz)(3)}Cl(2)(THF) (17) containing an apical carbanion. Reaction of the analogous phenol-based ligand (Me(2)pz)(2)CHArOH (ArO = 2-O-3,5-C(6)H(2)(t)Bu(2)) with CrCl(3)(THF)(3) gave Cr{(Me(2)pz)(2)CHArOH}Cl(3) (19) whereas the corresponding reaction with CrCl(2)(THF)(2) unexpectedly gave the Cr(III) phenolate derivative Cr{(Me(2)pz)(2)CHArO}Cl(2)(THF) (20) which could also be prepared from CrCl(3)(THF)(3) and the sodiated ligand [Na{(Me(2)pz)(2)CHArO}(THF)](2). Reaction of the corresponding ether (Me(2)pz)(2)CHArOMe with CrCl(3)(THF)(3) or CrCl(2)(THF)(2) gave Cr{(Me(2)pz)(2)CHArOMe}Cl(3) (23) and Cr{(Me(2)pz)(2)CHArOMe}Cl(2)(THF) (24), respectively. The catalytic performance in ethylene oligomerisation/polymerisation of all of the new Cr(II) and Cr(III) complexes was evaluated. Most of the complexes showed high activity, but produced a Schultz Flory distribution of alpha-olefins. Compound 23 had an exceptionally low alpha value of 0.37 and showed a preference for 1-hexene and 1-octene formation. While replacing a secondary amine (10-13) for a tertiary amine (15-16) resulted in loss of catalytic activity, replacing a phenol (19) for an anisole (23) group afforded a more selective and more active catalyst. Changing from MAO to DIBAL-O as cocatalyst induced a switch in selectivity to ethylene polymerisation. PMID- 20354619 TI - Palladium complexes with a tridentate PNO ligand. Synthesis of eta1-allyl complexes and cross-coupling reactions promoted by boron compounds. AB - The iminophosphine 2-(2-Ph(2)P)C(6)H(4)N=CHC(6)H(4)OH (P-N-OH) reacts with [Pd(mu Cl)(eta(3)-C(3)H(5))](2) yielding [PdCl(P-N-O)] and propene. In the presence of NEt(3), the reaction of P-N-OH with [Pd(mu-Cl)(eta(3)-1-R(1),3-R(2)C(3)H(3))](2) (R(1) = R(2) = H, Ph; R(1) = H, R(2) = Ph) affords the eta(1)-allyl derivatives [Pd(eta(1)-1-R(1),3-R(2)C(3)H(3))](P-N-O)] (R(1) = R(2) = H: 1; R(1) = H, R(2) = Ph: 2; R(1) = R(2) = Ph: 3). In solution, the complexes 1 and 3 undergo a slow dynamic process which interconverts the bonding site of the allyl ligand. The X ray structural analysis of 1 indicates a square-planar coordination geometry around the palladium centre with a P,N,O,-tridentate ligand and a sigma bonded allyl group. The complexes [PdR(P-N-O)] (R = C(6)H(4)Me-4, C[triple bond]CPh) react slowly with p-bromoanisole in the presence of p-tolylboronic acid to give [PdBr(P-N-O)] and the coupling product RC(6)H(4)OMe-4. The latter reactions also proceed at a low rate under catalytic conditions. The coupling of allyl bromide with p-tolylboronic acid is catalyzed by [PdCl(P-N-O)]/K(2)CO(3) to give 4 allyltoluene. PMID- 20354620 TI - A quantum chemistry investigation on the structure of lanthanide triflates Ln(OTf)3 where Ln = La, Ce, Nd, Eu, Gd, Er, Yb and Lu. AB - Density functional theory has been used to probe the electronic structure, coordination number, optical properties and the vibration spectra of monolanthanide trifluoromethane sulfonate Ln(OTf)(3) complexes where Ln = La, Ce, Nd, Eu, Gd, Er, Yb and Lu. The study reveals that the OTf group is bonded to Ln as a bidentate ligand. TDDFT calculations show that, for La(OTf)(3), MLTC and HOMO-LUMO transitions in the UV-vis are strongly bathochromically shifted compared to those of Lu(OTf)(3.). PMID- 20354621 TI - Solvothermal syntheses, crystal structures and luminescence properties of three new lanthanide sulfate fluorides. AB - Three novel lanthanide sulfate fluorides of formulae [C(4)H(16)N(3)](6)[Sm(4)F(2)(SO(4))(14)] 1 and LnFSO(4).H(2)O (Ln = Tb 2; Nd 3) have been synthesized solvothermally and structurally characterized by single crystal X-ray diffraction, IR, TGA, SEM, and ICP. Single crystal X-ray diffraction reveals that compound 1 crystallizes in the triclinic crystal system, with space group P-1 and cell dimensions: a = 11.1988(9), b = 11.4073(9), c = 16.2666(13) A, alpha = 89.9010(10) degrees, beta = 82.4060(10) degrees, gamma = 67.7570(10) degrees, V = 1903.9(3) A(3), Z = 1. Both compounds 2 and 3 crystallize in the monoclinic crystal system, with the space group P2(1)/n and cell dimensions: a = 5.0014(7), b = 7.3769(11), c = 11.6508(17) A, beta = 96.692(2) degrees, V = 426.93(11) A(3), Z = 4 for 3; a = 4.9948(5), b = 7.3684(7), c = 11.6366(12) A, beta = 96.6720(10) degrees, V = 425.37(7) A(3), Z = 4 for 3. The structure of 1 consists of a novel isolated large Z-type heteropolyanion [Sm(4)F(2)(SO(4))(14)](18-) and full protonated organic amine cations. The chains are held together by hydrogen bond interactions involving the hydrogen of the amine and the framework oxygen. The compounds 2 and 3 are isostructural and their structures feature a three-dimensional network constructed from the left-handed and the right-handed helical channels which are connected by SO(4)(2-) groups using 6-membered rings and 4-membered rings. PMID- 20354622 TI - Pressure-dependent luminescence spectroscopy of molybdenum(IV) oxo complexes. AB - Luminescence spectra are reported for trans-[MoOCl(CN-t-Bu)(4)]BPh(4) and trans [MoOF(pyridine)(4)]BPh(4). The maxima of the broad luminescence bands are at energies of 12000 and 13000 cm(-1), respectively. Resolved vibronic structure involves the metal-oxo stretching mode with a vibrational frequency of approximately 950 cm(-1) (Raman) in both compounds. The pressure behavior of the luminescence bands shows a distinct difference: a blue shift of +12 cm(-1) kbar( 1) is observed for [MoOCl(CN-t-Bu)(4)]BPh(4), and a red-shift of -8 cm(-1) kbar( 1) is obtained for [MoOF(pyridine)(4)]BPh(4). At pressures above 25 kbar, the luminescence maximum of [MoOCl(CN-t-Bu)(4)]BPh(4) shows a change from a blue shift to a red-shift and the Raman peak corresponding to the metal-oxo stretching mode at 954 cm(-1) becomes broad and its maximum decreases with increasing pressure, leading to a strong deviation from the linear increase of +0.24 cm(-1) kbar(-1) observed at pressures below 25 kbar. These unusual pressure effects are rationalized in terms of the influence of pressure on the metal-ligand bonds and oxo-metal-ligand angles using DFT calculations. PMID- 20354623 TI - Theoretical study on the tetranuclear endohedral vanadyl carboxylates with guest switchable redox properties and large polarizability. AB - The polarizability and redox properties for the tetranuclear vanadium-oxide carboxylates have been investigated using density functional theory (DFT). These so-called inorganic crown ethers possess large polarizabilities, which are equivalent to fullerene and generate large polarization on the guest anions into the host. The dipole-induced dipole interaction between the host and the guest anions induces charge transfer from the guest to the host, which is enhanced with the increasing polarization. Moreover, the redox potentials are sensitive to different guests inside the host bowl, and they shift negatively as compared to the isolated host bowl. In contrast, the modification of the methyl group by CH(2)tBu on the rim of the bowl has evoked higher polarizability (over 560 a.u.) with larger polarization on the guest anions and more negative redox potentials. The weak interaction energies in accord with the organic crown ether incorporating alkali metal ions indicate that the guest anions can move freely inside and outside the host bowl, so this kind of inorganic crown ether may exhibit potential guest-switchable redox properties based on reversible complexation-decomplexation and will be expected to find applications in ion recognition and selectivity studies based on the sensitivity to different guests. PMID- 20354624 TI - Coordination chemistry of platinum and palladium in the solid-state: synthesis of imidazole and pyrazole complexes. AB - Solid-state reactions of palladium(II) and platinum(II) chloride complexes with imidazole (Him) and pyrazole (Hpz) or their hydrochloride salts are shown to produce metal complex salts and coordination compounds. Thus, K(2)[MCl(4)] or MCl(2) can be ground with imidazolium chloride ([H(2)im]Cl) to produce the salts [H(2)im](2)[MCl(4)] (M = Pd, 1; Pt, 5), which can then be dehydrochlorinated in the solid state to produce the coordination compounds trans-[PdCl(2)(Him)(2)] 3 or cis-[PtCl(2)(Him)(2)] 6. The complex cis-[PdCl(2)(Him)(2)] 2 is produced when Pd(OAc)(2) is ground with [H(2)im]Cl. Reaction of platinum chloride reagents with imidazole (Him) also produces cis-[PtCl(2)(Him)(2)] 6, but reaction of imidazole with analogous palladium chloride reagents first produces [Pd(Him)(4)]Cl(2) 4 which then slowly converts to trans-[PdCl(2)(Him)(2)] 3. Grinding pyrazolium chloride with K(2)[MCl(4)] produces [H(2)pz](2)[MCl(4)] (M = Pd, 7; Pt, 10), which may also be dehydrochlorinated in the solid state to produce the coordination compounds trans-[PdCl(2)(Hpz)(2)] 8 or cis-[PtCl(2)(Hpz)(2)] 11. Grinding K(2)[PdCl(4)] or PdCl(2) with pyrazole gives [Pd(Hpz)(4)]Cl(2) 9, which is then slowly converted into trans-[PdCl(2)(Hpz)(2)] 8. Grinding PtCl(2) with Hpz generates [Pt(Hpz)(4)]Cl(2) 12, but using K(2)PtCl(4) as the metal source does not generate the same product. The single-crystal structures of 8, a new polymorph of 11 and [H(2)pz](2)[PtCl(6)].2H(2)O (isolated as a decomposition product) are reported for the first time, and the structures of 5 and 10 have been solved ab ibitio from XRPD data. PMID- 20354625 TI - Site specific ligand substitution in cubane-type Mo3FeS(4)(4+) clusters: kinetics and mechanism of reaction and isolation of mixed ligand Cl/SPh complexes. AB - The synthesis, crystal structure and solution characterization of the cubane-type [Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3)] (1) (dmpe = 1,2-bis(dimethylphophane-ethane)) cluster are reported and the ligand substitution processes of chloride by thiophenolate investigated. The kinetics and the intimate mechanism of these substitutions reveal that compound 1 undergoes a number of Fe and Mo site specific ligand substitution reactions in acetonitrile solutions. In particular, PhS(-) coordination at the tetrahedral Fe site proceeds in a single resolved kinetic step whereas such substitutions at the Mo sites proceed more slowly. The effect of the presence of acids in the reaction media is also investigated and reveals that an acid excess hinders substitution reactions both at the Fe and Mo sites; however, an acid-promoted solvolysis of the Fe-Cl bonds is observed. Electrospray ionization (ESI) and tandem (ESI-MS/MS) mass spectrometry allow the identification of all the reaction intermediates proposed on the basis of stopped flow measurements. The distinctive site specific reactivity made it possible to isolate two new clusters of the Mo(3)FeS(4)(4+) family featuring mixed chlorine/thiophenolate ligands, namely Mo(3)S(4)(FeSPh)(dmpe)(3)Cl(3) (2) and [Mo(3)S(4)(FeSPh)(dmpe)(3)(SPh)(3)] (3). A detailed computational study has also been carried out to understand the details of the mechanism of substitution at the M-Cl (M = Mo and Fe) bonds as well as the solvolysis at the Fe-Cl sites, with particular emphasis on the role of acids on the substitution process. The results of the calculations are in agreement with the experimental observations, thus justifying the non-existence of an accelerating effect of acids on the thiophenolate substitution reaction, which differs from previous proposals for the Fe(4)S(4) and MoFe(3)S(4) clusters and some related compounds. PMID- 20354626 TI - The crystal structures of the low-temperature and high-pressure polymorphs of nitric acid. AB - A new high-pressure phase of pure nitric acid (HNO(3)) has been characterised at 1.6 GPa at room temperature by high-pressure neutron powder and X-ray single crystal diffraction techniques. This is the first crystalline phase obtained upon compression of liquid nitric acid at room temperature and appears to be the stable phase up to pressures of at least 4 GPa. The crystal structure of this new phase shows some similarities to that of the low-temperature phase of nitric acid at ambient pressure, which has been redetermined as part of this study. Both structures share a herringbone packing of hydrogen-bonded molecular catemers, although the presence of disorder within the hydrogen bonds within one of the catemers of the low-temperature phase makes its structure comparatively more complex. PMID- 20354627 TI - Comparative investigation of the solution species [U(CO3)5]6- and the crystal structure of Na6[U(CO3)5].12H2O. AB - The limiting U(IV) carbonate species in aqueous solution was investigated by comparing its structure parameters with those of the complex preserved in a crystal structure. The solution species prevails in aqueous solution of 0.05 M U(IV) and 1 M NaHCO(3) at pH 8.3. Single crystals of Na(6)[U(CO(3))(5)].12H(2)O were obtained directly from this mother solution. The U(IV) carbonate complex in the crystal structure was identified as a monomeric [U(CO(3))(5)](6-) anionic complex. The interatomic distances around the U(IV) coordination polyhedron show average distances of U-O = 2.461(8) A, U-C = 2.912(4) A and U-O(dist) = 4.164(6) A. U L(3)-edge EXAFS spectra were collected from the solid Na(6)[U(CO(3))(5)].12H(2)O and the corresponding solution. The first shell of the Fourier transforms (FTs) revealed, in both samples, a coordination of ten oxygen atoms at an average U-O distance of 2.45 +/- 0.02 A, the second shell originates from five carbon atoms with a U-C distance of 2.91 +/- 0.02 A, and the third shell was fit with single and multiple scattering paths of the distal oxygen at 4.17 +/- 0.02 A. These data indicate the identity of the [U(CO(3))(5)](6-) complex in solid and solution state. The high negative charge of the [U(CO(3))(5)](6-) anion is compensated by Na(+) cations. In solid state the Na(+) cations form a bridging network between the [U(CO(3))(5)](6-) units, while in liquid state the Na(+) cations seem to be located close to the anionic complex. The average metal-oxygen distances of the coordination polyhedron show a linear correlation to the radius contraction of the neighbouring actinide(IV) ions and indicate the equivalence of the [An(CO(3))(5)](6-) coordination within the series of thorium, uranium, neptunium and plutonium. PMID- 20354628 TI - Towards Langmuir-Blodgett films of magnetically interesting materials: solution equilibria in amphiphilic iron(II) complexes of a triazole-containing ligand. AB - As a first step towards amphiphilic spin crossover (SCO) systems where the hydrophobic part of the system is introduced by a non-coordinating anion (i.e. where no modification of the ligands to introduce hydrophobic substituents is required), [Fe(II)(OH(2))(2)(C(16)SO(3))(2)] and [Co(II)(OH(2))(2)(C(16)SO(3))(2)] have been prepared and reacted with the triazole-containing ligands adpt and pldpt (C(16)SO(3) = hexadecanesulfonate anion, adpt = 4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole, pldpt = 4-pyrrolyl-3,5 bis(2-pyridyl)-1,2,4-triazole). In the solid state, two HS complexes of the form [Fe(II)(Rdpt)(2)(C(16)SO(3))(2)] and two of the form [Co(II)(Rdpt)(2)(CH(3)OH)(2)](C(16)SO(3))(2) are obtained, even when a six-fold excess of ligand is used (Rdpt = adpt or pldpt). In solution, the cobalt complexes remain in this form as evidenced by colour, Visible/NIR and IR spectroscopy. For the iron complexes, there is an equilibrium in solution between the neutral high-spin form of the complex [Fe(II)(Rdpt)(2)(C(16)SO(3))(2)] and the dicationic low-spin tris form [Fe(II)(Rdpt)(3)](C(16)SO(3))(2). Polar solvents favour the dicationic form, while less polar solvents favour the neutral form (as evidenced by solution colour and solution IR spectroscopy). Visible/NIR spectroscopy and Evans' method NMR spectroscopy show the equilibrium can be shifted towards the [Fe(II)(Rdpt)(3)](C(16)SO(3))(2) form by adding additional ligand to the solution. The X-ray crystal structures of [Fe(II)(adpt)(2)(C(16)SO(3))(2)] and [Co(II)(adpt)(2)(CH(3)OH)(2)](C(16)SO(3))(2).1.33CH(3)OH are presented. [Fe(II)(adpt)(2)(C(16)SO(3))(2)] has a 2D bilayer structure with alternating layers of polar Fe(adpt)(2) centres, and hydrophobic alkyl chains. The complex cations in [Co(II)(adpt)(2)(CH(3)OH)(2)](C(16)SO(3))(2).1.33CH(3)OH form 1-D columns in the solid state. The capacity of the amphiphilic complexes [Fe(II)(pldpt)(2)(C(16)SO(3))(2)] and [Fe(II)(adpt)(2)(C(16)SO(3))(2)] to self assemble has been probed at the air-water interface using Langmuir techniques. The pertinent pressure-area isotherms reveal only a low tendency of the complexes to form films. PMID- 20354629 TI - Some reactions of an eta3-tetracyanobutadienyl-ruthenium complex. AB - In the eta(3)-butadienyl complex Ru{eta(3)-C(CN)(2)CPhC=C(CN)(2)}(PPh(3))Cp 1, which is formed from Ru(C[triple bond]CPh)(PPh(3))(2)Cp and tcne, a CN group reacts with MeO(-) to give the methoxy-amide Ru{NH=C(OMe)C(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 2, in which the NH has displaced the C=C from the Ru centre with formation of a RuC(3)N ring. "Click addition" of azide to a CN group in 1 gives the oligomeric tetrazolato complex Ru{N(3)N[Na(OEt(2))]=CC(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 3, also containing a RuC(3)N ring. Salt-elimination reactions of 3 with MeOTf, FeCl(dppe)Cp, RuCl(dppe)Cp* and trans-PtCl(2){P(tol)(3)}(2) result in selective substitution at one nitrogen atom of the RuC(3)N ring. Geometries of 1 and the anion in 3 were computed by DFT methods. Preferences for CN groups attacked in the nucleophilic and cycloaddition reactions of 1 are supported by NBO calculations. Alkylation of 1 in reactions with 1,2-dimethoxyethane gave two isomers of Ru{N(3)[CH(CH(2)OMe)(OMe)]N=CC(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 8 and 9, differing in the sites of attachment of the alkyl group, likely by radical processes. The molecular structures of eight complexes are reported, including a re determination of 1. Computed NMR chemical shifts are used to reassign the butadienyl carbon resonances in the (13)C NMR spectrum of 1. PMID- 20354633 TI - Topical and systemic photoprotection. PMID- 20354634 TI - Chronic sun damage and the perception of age, health and attractiveness. AB - Young and healthy-looking skin is a feature that is universally admired and considered attractive among humans. However, as we age, skin condition deteriorates due to a variety of intrinsic and extrinsic factors determined not only by genetics and physiological health but also by behaviour and lifestyle choice. As regards the latter, cumulative, repeated exposure to solar ultraviolet radiation (UVR) is linked intrinsically to the induction of specific types of skin cancer and the expression of cutaneous damage markers responsible for the majority of the visible signs of skin ageing. Here we review empirical evidence for skin-specific effects of chronic UVR exposure and relate it to perception of visible skin condition. In contrast to other dermatological accounts, we stress an evolutionary psychology context in understanding the significance of age related changes in visible skin condition in human social cognition and interaction. We suggest that the "marriage" of the scientific fields of skin biology and evolutionary psychology provides a modern, powerful framework for investigating the causes, mechanisms and perception of chronic sun damage of skin, as it explains the human obsession with a youthful and healthy appearance. Hence, it may be that these insights bring true emotional impetus to the adoption of sun protection strategies, which could conceivably impact skin cancer rates in coming years. PMID- 20354635 TI - Knowledge, motivation, and behavior patterns of the general public towards sun protection. AB - The general public has long been educated about the harms of ultraviolet (UV) exposure and the benefits of photoprotection. Many organizations have worked in close collaboration to deliver the photoprotection message through a variety of programs. Most address the health-related consequences of UV radiation, although appearance-based strategies have also been initiated. As is common with preventative health measures, these intervention efforts have not resulted in meaningful changes in public behavior despite providing seemingly adequate knowledge to do so. Behaviors are often difficult to change on a societal, personal, and biological level. Within these categories, there are unique reasons for the unsatisfactory outcome with photoprotection such as (1) tan is perceived as beautiful, (2) the knowledge conveyed is often superficial, (3) there is a lack of immediate risk/reward, and (4) UV has reinforcing effects on mood. We propose that better results could be achieved by creating interventions focused on demographic subsets of the population. Specific techniques include anti tanning legislature, age or gender-based screening campaigns, anti-tan beauty campaigns, and UV photography. Future photoprotection messages should shift from purely promoting knowledge to inspiring improvements in behavior with targeted strategies. PMID- 20354636 TI - Molecular modifications of dermal and epidermal biomarkers following UVA exposures on reconstructed full-thickness human skin. AB - Ultraviolet A (UVA) radiation adversely affects skin health and appearance via multiple molecular pathways. Biologically relevant UVA damage are classified as short-term effects (e.g. formation of reactive oxygen species [ROS], inflammation, photo-oxidation, DNA damage, immunosuppression, photoallergy and cell-mediated contact hypersensitivity) or long-term effects (elastosis, photoageing and photocarcinogenesis). Single and chronic experimental exposure to UVA are limited in humans by ethical concerns, and furthermore it is impossible to quantify long-term endpoints such as photoageing over the life-span of a human volunteer. The aim of the present study was to investigate the biological relevance of the Phenion FT skin model for use in photobiological studies. Biological responses to acute and repeated UVA exposures were investigated by monitoring the kinetics of gene expression during the post-irradiation period. By using a dynamic approach, we were able to define early and stable markers of UVA induced effects that could be predictive of UVA damage in vivo. The transcriptomic approach applied to 3D human tissues appears to be an encouraging method for gaining a deeper understanding of the UVA effects on skin and for studying the dermal response with non-invasive techniques. PMID- 20354637 TI - In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin. AB - Epidermal keratinocytes are critical targets for UV-induced genotoxicity as their transformation by sunlight overexposure can lead to skin cancer such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Therefore, assessment of photoprotection should involve early markers associated with DNA photodamage. Here, the same normal human keratinocytes either in monoculture (KC) or in full thickness reconstructed skin (RS) were compared with respect to their response to simulated solar UV (SSUV) exposure. Irradiation conditions (spectral power distribution and doses) were designed to mimic environmental zenithal UV from sunlight. At doses where survival was higher than 80%, comet assay showed more single strand breaks (SSB) and cyclobutane pyrimidine dimers (CPD) in keratinocytes in RS than in KC one hour post-exposure. The transcription factor p53 was activated in both models. While in KC p53 accumulation displayed a linear dose-dependency up to 24 h post-exposure, in RS it followed a bell-shaped profile and reverted to its basal rate. QRT-PCR demonstrated that among genes controlled by p53, P21 and MDM2 were clearly induced by SSUV in KC, whereas GADD45 expression was strongly and almost exclusively up-regulated in RS. Nrf2-dependent antioxidant genes (Ferritin light chain, NQO1) were only induced in RS, yet at low doses for NQO1. In vitro models such as KC or RS allowing the development of quantitative methodologies should be used as surrogates for in vivo tests assessing photogenotoxicity. PMID- 20354639 TI - Ultraviolet filters. AB - The chemistry, photostability and mechanism of action of ultraviolet filters are reviewed. The worldwide regulatory status of the 55 approved ultraviolet filters and their optical properties are documented. The photostabilty of butyl methoxydibenzoyl methane (avobenzone) is considered and methods to stabilize it in cosmetic formulations are presented. PMID- 20354638 TI - Comparison between UV index measurements performed by research-grade and consumer products instruments. AB - Ultraviolet radiation (UVR) exposure, skin cancer and other related diseases are not just subjects of scientific literature. Nowadays, these themes are also discussed on television, newspapers and magazines for the general public. Consequently, the interest in prevention of sun overexposure is increasing, as the knowledge of photoprotection methods and UVR levels. The ultraviolet index (UVI) is a well-known tool recommended by the World Health Organization to avoid harmful effects of UV sunlight. UVI forecasts are provided by many national meteorological services, but local UVI measurements can provide a more realistic and appropriate evaluation of UVR levels. Indeed, as scientific instruments are very expensive and difficult to manipulate, several manufacturers and retail shops offer cheap and simple non-scientific instruments for UVI measurements, sometimes included in objects of everyday life, such as watches, outfits and hand held instruments. In this work, we compare measurements provided by several commercial non-scientific instruments with data provided by a Bentham spectrometer, a very accurate sensor used for UV measurements. Results show that only a few of the instruments analyzed provide trustworthy UVI measurements. PMID- 20354640 TI - The long way towards the ideal sunscreen--where we stand and what still needs to be done. AB - The magnitude and quality of UV protection provided by topical sun products have improved considerably over the past three decades. As our knowledge and understanding of sun protection requirements increases, product and testing technologies advance and new sunscreen molecules and technologies become available. The biannual London Sun Protection Conference has monitored this development over the last two decades. The 2009 edition of the conference (June 3 and 4) was entitled "Perfection of Protection". This paper, based on our talk given at the conference, tries to answer the question about the "ideal sunscreen" and explores four key requirements of good UV protection regarding where we stand on a ranking scale between poor and perfect, and what still needs to be done. Technology is leading with a rating of 80%, Assessment/measurement follows at 70%, Norms/standards around 50% and Compliance ranks only around 30% between poor and perfect. UV filters are the heart of the product technology. Besides UVB filters, plenty of UV filters for UVA II and UVA I protection are now available in most parts of the world, except the USA. Although the Sun Protection Factor is well established and various methods have been developed for assessment of UVA protection, the performance measurement of sunscreens is still far from perfect. On the other hand, the high bar for achieving the highest UVA protection in the various classification systems released recently in Europe (2006) and the USA (2007) already helped to increase the protection considerably. The greatest problem however, remains poor compliance. Providing cosmetically pleasing formulations that people like to wear and communicating what sunscreens are and how they work are key elements in improving UV protection. PMID- 20354641 TI - Percutaneous absorption with emphasis on sunscreens. AB - Sunscreens are widely used products. When recreationally used they are applied to large areas of the skin repeatedly. In moisturizers and foundation it is common to find sun protective ingredients, in these cases the product is usually applied to smaller areas but often done daily. Active ingredients in sunscreens can be absorbed by the skin. Percutaneous absorption is an important factor to take into consideration. There are several methods to measure the percutaneous absorption, both in vivo and/or in vitro. This paper will give an overview of the different methods. PMID- 20354642 TI - In vitro measurements of sunscreen protection. AB - The ultimate goal of in vitro measurements of sunscreen protection is replacement of invasive tests on human volunteer subjects. This requires validation of methods against a measurable in vivo benchmark, such as SPF. SPF is measured in the laboratory using artificial light sources that do not completely simulate sunlight. Once a method for in vitro measurements is validated, sunscreen protection against measured solar spectra may be achieved. Critical aspects of in vitro measurements of sun protection include the ability of substrates to emulate human skin, performance of instrumentation and use of correct algorithms to account for changes in sunscreen absorbance during irradiation. We have developed a dose-response model that accounts for changes in absorbance and facilitates evaluation of broad spectrum protection, as well as SPF, and provides an index of sunscreen photostability. PMID- 20354643 TI - Human safety review of "nano" titanium dioxide and zinc oxide. AB - Based on the current weight of evidence of all available data, the risk for humans from the use of nano-structured titanium dioxide (TiO(2)) or zinc oxide (ZnO) currently used in cosmetic preparations or sunscreens is considered negligible. There is a large body of information that when viewed in its entirety is considered as sufficient to demonstrate that these nano-structured ultraviolet (UV) filters, irrespective of various treatments (coatings) or crystalline structure, can be regarded as safe for use at concentrations up to 25% in cosmetic products to protect the skin from harmful effects of solar UV radiation. "Nano" TiO(2) and ZnO formulated in topically applied sunscreen products exist as aggregates of primary particles ranging from 30-150 nm in size. These aggregates are bonded such that the force of sunscreen product application onto the skin would have no impact on their structure or result in the release of primary particles. Multiple studies have shown that under exaggerated test conditions neither nano-structured TiO(2) nor ZnO penetrates beyond the stratum corneum of skin. Further, the distribution and persistence of these nano-structured metal oxides is the same compared to larger pigment-grade (i.e., >100 nm) particles, demonstrating equivalence in the recognition and elimination of such material from the body. Finally, the in vitro genotoxic and photogenotoxic profiles of these nano-structured metal oxides are of no consequence to human health. Whereas the most logical, straightforward conclusion based on data from internationally recognized guideline studies and current 20+ year history of human use is that nano-structured TiO(2) and ZnO are safe, there will continue to be questions as "nano" conjures images of technology gone awry. Despite this rather sober view, the public health benefits of sunscreens containing nano TiO(2) and/or ZnO outweigh human safety concerns for these UV filters. PMID- 20354644 TI - Sunscreens and occupation: the Austrian experience. AB - Since the nineteen fifties the attitude of the fair-skinned world population towards the sun has changed dramatically. Tanned skin, which before was regarded as the stigma of the underprivileged working classes, became fashionable and desirable. The science of photoprotection primarily focuses on ultraviolet exposure during leisure time activities, whereas ultraviolet radiation is still underestimated as a risk factor for UV-induced skin and eye problems. The actual discussion on the registration of UV-induced skin tumours as occupational diseases, however, has drawn more attention to this important issue. Ambient radiation, the working process itself and the photoprotective behaviour of an outdoor worker are the main factors which influence the actual UV exposure. However, the total risk for the development of actinic damage results from the interaction of both the occupational and the leisure time exposure. It is evident that there is a high need for photoprotective measures for outdoor workers. Topical sunscreens as a part of a comprehensive UV protection strategy for outdoor workers have to fulfil special requirements: reasonable price, high water resistance, non-sticky appearance. At present only a few products are available which meet these criteria. This is the reason why sunscreens are not so well accepted by outdoor workers. Great efforts have to be undertaken to improve sunscreen formulations and to convince people to apply them correctly and regularly. PMID- 20354645 TI - UVA protection labeling and in vitro testing methods. AB - The importance of adequate UVA protection is apparent with improved understanding of UVA-induced skin damage. This has led to the development of new sunscreen ingredients. A number of regulatory bodies or experts from the industry and academia have proposed methods to assess the efficacy of sunscreens against UVA radiation. In addition different proposals have been made regarding the labeling for UVA protection. The purpose of this paper is to describe several in vitro methods for measuring UVA protection of sunscreen products and to consider their validity. The different proposals in terms of UVA labeling are also presented and discussed. This review illustrates the need for standardization of the measurement conditions and harmonization to convey to consumers the most appropriate information on UVA protection. PMID- 20354646 TI - Sunscreens: the impervious path from theory to practice. AB - The preparation of commercial products able to protect the skin against damage from solar radiation requires safe and photo-stable stable UV-absorbing molecules with high extinction coefficients, prepared with solvents of the appropriate polarities and polarizabilities in formulas which allow the uniform spreading of the UV-absorbing substances. The products should also maintain the ingredients on the top of the skin and provide efficient scavenging activities against singlet oxygen and other directly or indirectly generated reactive oxygen species. Because of the high doses of UV used to test high SPF, simple and reproducible methods are needed to estimate the protection afforded by the product before risking the induction of severe burns to the volunteers, as can occur when the value of the product's SPF is smaller than the expected one. This paper describes several aspects of the preparation of commercial sunscreens. It also points out several of the hidden hypotheses which, when not tested, might lead to the overestimation of the protection factor of a product. PMID- 20354647 TI - Dose-dependent progressive sunscreens. A new strategy for photoprotection? AB - A new generation of UV filters has been developed that act by limiting the dose of radiation rather than by blocking a fraction of the solar irradiance on the skin surface. Such progressive sunscreens are based on the photochemical transformation of suitable precursors upon exposure to sunlight. Broadband sunscreens are thus generated "on demand", affording protection when, where, and to the extent that it is needed, providing higher protection to more exposed areas, and increasing the UV blocking capacity as the radiation dose increases. Encapsulation in silica particles isolates the precursors and transformation products, further improving the efficacy, safety, and environmental impact of the use of sunscreens. PMID- 20354648 TI - The FDA proposed solar simulator versus sunlight. AB - The US Food and Drug Administration is in the process of formulating final rules for sunscreen labeling and testing. They have adopted a version of the solar simulator standard proposed by COLIPA, a European cosmetic products trade association. From our files we have selected spectral data on several solar simulators that comply with the proposed rules and have compared these sources both one to another and to several standard solar spectra of Air Mass 1.0, 1.5, and 2.0. In doing so we have used additional spectral analysis procedures including examining the goodness of fit between each solar simulator spectrum and an Air Mass 1.0 (0 degrees zenith angle) solar spectrum. The index of goodness of fit ranges from approximately 78% to just over 90% compared to solar spectra representing other Air Masses of 1.5 and 2.0, the goodness of fit is lower. Unfortunately, one may not assume that complying with a standard assures that other solar simulators also complying will produce identical results. In fact, by our analysis, none of the solar simulators we examined would be expected to produce the same SPF as sunlight. PMID- 20354649 TI - How a calculated model of sunscreen film geometry can explain in vitro and in vivo SPF variation. AB - Spectroscopic in vitro assay has recently gained importance for UVA protection, or even for SPF assessment, as manufacturers are increasingly keen to replace in vivo by in vitro tests. These assays are based on transmission UV spectroscopy of a known amount of sunscreen product spread onto an ultraviolet-transparent substrate. In the most recent European publications or methods, the preferred substrate is a roughened PMMA plate. We demonstrated in a previous work the importance of a strict control of plate roughness to ensure reproducibility and repeatability of in vitro results. In the present paper, we studied the effect of varying the thickness of applied sunscreen on low or high plate roughness. Two optimal sunscreen amounts, 0.75 mg cm(-2) for low roughness and 1.2 mg cm(-2) for high roughness, could achieve in vitro SPF close to in vivo SPF. The UV absorption spectra were measured and analyzed, via a mathematical model of irregular film geometry based on a well-known statistical distribution, the gamma law function. Our calculations show the relevance of the model to describe correctly the sunscreen film geometry evolution according to different in vitro spectra changes. Inversely, adjustment of the film geometry to fit with a set of in vivo SPF results allows us to extrapolate the real UV absorption spectra of sunscreens applied on the skin at 2 mg cm(-2). A high plate roughness, preferably a moulded plate for reproducibility, is required to obtain the closest agreement between in vitro and in vivo sunscreen absorption spectra over the entire UV waveband. PMID- 20354650 TI - Filter-filter interactions. Photostabilization, triplet quenching and reactivity with singlet oxygen. AB - In most sunscreens, the presence of two UV filters usually leads to synergistic effects regarding both the final performance and photostabilization of the active principles. However, this may also result in an accelerated decomposition if a photoreaction occurs between the single components. Thus, the understanding of photophysics and photochemistry of UV filter combinations is important to improve sunscreen photostability. In this context, photoreactivity of a commonly used UVA filter, namely tert-butylmethoxydibenzoylmethane (BM-DBM, also known as avobenzone, Parsol 1789, etc.), has been studied in the presence of six commercial solar filters: octyl methoxycinnamate, bis-ethylhexyloxyphenol methoxyphenyl triazine, octocrylene, diethylamino hydroxybenzoyl hexyl benzoate, octyl triazone and dioctyl butamido triazone. To achieve this goal, a mechanism based strategy has been designed in order to investigate the photostability of sunscreens in a more systematic way, taking into account different processes: tautomerization of BM-DBM, formation of triplet excited state of BM-DBM in its diketo form and its quenching in the presence of UV filters, reactivity of UV filters under triplet photosensitization, quenching of singlet oxygen by UV filters and degradation of the latter under singlet oxygenation conditions. PMID- 20354651 TI - Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent. AB - Photoprotection is essential to prevent the deleterious effects of ultraviolet (UV) light, including skin cancer, photoaging and immunosuppression. Photoprotective agents can be classified according to their main mechanism of action. Some of them absorb or deflect UV photons (sunscreens), whereas others prevent or fix the deleterious effects of UV exposure. Here, we review recent evidence on the cellular and molecular mechanisms underlying the photoprotective effect of a Polypodium leucotomos fern extract (PL). PL is a natural mixture of phytochemicals endowed with powerful antioxidant properties. Its short-term effects include inhibition of reactive oxygen species production induced by UV radiation, DNA damage, isomerization and decomposition of trans-urocanic acid, prevention of UV-mediated apoptosis and necrosis, as well as degradative matrix remodeling, which is the main cause of photoaging. These short-term effects translate into long-term prevention of photoaging and photocarcinogenesis. A striking property is that PL can exert its effect when administered orally. Together, these effects postulate PL as a natural photoprotective agent and a potential adjuvant to phototherapy for various skin diseases. PMID- 20354652 TI - Vitamin D-fence. AB - The role of vitamin D in the immune system is complex. Vitamin D is produced in the skin following exposure to ultraviolet radiation. There is compelling evidence that vitamin D compounds protect against ultraviolet radiation-induced DNA damage and immune suppression, suggesting it may be beneficial as a skin cancer preventive agent. However, vitamin D has many modulatory effects on the immune system and it has in fact been suggested that the immune suppression generally attributed to the UVB portion of sunlight is mediated through vitamin D. Here we describe the role of vitamin D compounds as "defence" molecules against UVR-induced damage, and investigate both sides of the "fence" regarding the effects of vitamin D compounds and the immune system. PMID- 20354653 TI - UV exposure and protection against allergic airways disease. AB - Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity. Allergen-specific IgE levels control the immediate response whilst the interplay between airway mucosal antigen presenting cells, Th2 effector cells and CD4+CD25+ regulatory T cells control the late phase, cell-mediated response. Using two experimental systems in mice with ovalbumin and papain, respectively, as the allergens, UV irradiation of skin prior to allergen sensitisation reduced the expression of allergic airways disease, particularly the late phase response. In this review, the reduced Th2 driven, asthma-like responses in respiratory tissues of UV-irradiated mice are detailed. Possible mechanisms of UV regulation are debated. The potential beneficial effects of UV irradiation of skin in controlling allergic airways disease are discussed. This review gives some scientific understanding to century old anecdotal reports that beach and mountain resort holidays associated with increased UV exposure are beneficial in asthma treatment. PMID- 20354654 TI - Photoprotective effects of nicotinamide. AB - Sun protective measures can reduce numbers of both precancerous actinic keratoses and cutaneous squamous cell carcinomas within relatively short periods of time even in high-risk populations. Sunscreens, which tend to provide greater protection against shortwave UVB than against longer wavelength UVA radiation, can however provide only partial protection from the mutagenic and immune suppressive effects of sunlight. In large part, this reflects poor compliance with proper sunscreen application and reapplication. Skin cancer is by far the most common malignancy in Caucasian populations, and additional strategies to reduce the morbidity and economic burden of this disease are now urgently needed. Nicotinamide, the amide form of vitamin B3, is an inexpensive agent which is used for a variety of dermatological applications with little or no toxicity even at high doses. Nicotinamide has photoprotective effects against carcinogenesis and immune suppression in mice, and is photoimmunoprotective in humans when used as a lotion or orally. UV irradiation depletes keratinocytes of cellular energy and nicotinamide, which is a precursor of nicotinamide adenine dinucleotide, may act at least in part by providing energy repletion to irradiated cells. PMID- 20354655 TI - The two faces of metallothionein in carcinogenesis: photoprotection against UVR induced cancer and promotion of tumour survival. AB - Metallothionein is a multi-functional protein that protects the host against toxic heavy metals. Under stressful situations it can protect against oxidative damage, contribute to tissue repair, modulate immune responses and limit inflammatory processes. Recently, metallothionein's role in ultraviolet radiation (UVR)-induced injury has been investigated. These studies have shown that when metallothionein is upregulated following exposure to UVR, it can protect against UVR-induced damage and the subsequent development of skin cancer. We propose that this initial protection is achieved through its anti-oxidant role resulting in reduced oxidative stress, reduced apoptosis, reduced NFkappaB activation and enhanced repair of DNA damage. However, once UVR-induced neoplasia has occurred, the cancer cells can hijack metallothionein's protective functions, resulting in increased tumour progression and malignancy. These two discordant sets of attributes are context-dependent, and represent the two faces of metallothionein. PMID- 20354656 TI - Dietary glucoraphanin-rich broccoli sprout extracts protect against UV radiation induced skin carcinogenesis in SKH-1 hairless mice. AB - Feeding broccoli sprout extracts providing daily doses of 10 micromol of glucoraphanin to SKH-1 hairless mice with prior chronic exposure to UV radiation (30 mJ cm(-2) of UVB, twice a week, for 17 weeks) inhibited the development of skin tumors during the subsequent 13 weeks; compared to the controls, tumor incidence, multiplicity, and volume were reduced by 25, 47, and 70%, respectively, in the animals that received the protective agent. PMID- 20354657 TI - Mice drinking goji berry juice (Lycium barbarum) are protected from UV radiation induced skin damage via antioxidant pathways. AB - The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV induced immunosuppression, and against suppression induced by the mediator, cis urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans. PMID- 20354658 TI - Oestrogen receptor-beta signalling protects against transplanted skin tumour growth in the mouse. AB - We have reported previously that a deficiency in signalling by the non-classical oestrogen receptor-beta (Er-beta) exacerbates immunosuppression by UV radiation in the mouse. Because photoimmune suppression is a risk factor for skin cancer development, we hypothesize that Er-beta deficiency will promote skin tumour growth. Therefore we have blocked Er signalling pharmacologically in the Skh:hr-1 hairless mouse by topical treatments with the Er antagonist ICI 182,780, and genetically in haired mice by using the specific Er-beta knockout mouse (targeted mutation of the Er-beta), and examined the growth rate of 3 transplantable skin tumour cell lines in their syngeneic host mice. Two UV-induced squamous cell carcinoma (SCC) cell lines transplanted into the Skh:hr-1 recipients were found to have regressor qualities that were delayed by prior immunosuppressive solar simulated UV (SSUV) irradiation. For the T79 SCC, regression was significantly further delayed by combined pretreatment with SSUV+ICI 182,780, and the diameters of the surviving tumours were slightly larger. For the KL3.0 SCC, both SSUV and combined SSUV+ICI 182,780 pretreatments completely inhibited tumour regression, and resulted in significantly greater tumour diameters than in unirradiated recipient mice. In heterozygous Er-beta deficient mice (Er-beta+/-), the B16/F10 melanoma grew progressively and significantly faster than in the wild type control mice (C57BL/6), and growth rate was accelerated by prior SSUV irradiation. Homozygous Er-beta-/- mice supported the most rapid B16/F10 growth that was further accelerated by prior SSUV irradiation. Therefore Er signalling, specifically by Er-beta, has a natural endogenous protective role against skin tumour growth, probably mediated via immunological pathways. PMID- 20354660 TI - Radiotherapy for oligometastatic disease in patients with spinal cord compression (MSCC) from relatively radioresistant tumors. AB - BACKGROUND: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC). Patients with relatively radioresistant tumors and oligometastatic disease may benefit from more intensive therapies (surgery, high precision radiotherapy). If such therapies are not available, one can speculate whether patients benefit from dose escalation beyond the standard regimen 30 Gy in ten fractions. PATIENTS AND METHODS: Of 206 patients with MSCC from relatively radioresistant tumors (renal cell carcinoma, colorectal cancer, malignant melanoma), 51 had oligometastatic disease (no visceral or other bone metastases, involvement of only one to three vertebrae). In this subset, 21 patients receiving 30 Gy in ten fractions were retrospectively compared to 30 patients receiving higher doses. Seven further potential prognostic factors were investigated: age, gender, tumor type, performance status, interval from tumor diagnosis to radiotherapy of MSCC, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. RESULTS: Motor function improved in 52% of patients after 30 Gy and 40% after higher doses (p = 0.44). On multivariate analysis, functional outcome was associated with interval from tumor diagnosis to radiotherapy (p = 0.020). 1-year local control rates were 84% after 30 Gy and 82% after higher doses (p = 0.75). No factor was associated with local control. 1-year survival rates were 76% after 30 Gy and 63% after higher doses (p = 0.52). On multivariate analysis, survival was associated with performance status (p = 0.022) and interval from tumor diagnosis to radiotherapy (p = 0.039), and almost with pretreatment ambulatory status (p = 0.069). CONCLUSION: Dose escalation beyond 30 Gy in ten fractions did not improve motor function, local control, and survival in MSCC patients with oligometastatic disease from relatively radioresistant tumors. PMID- 20354661 TI - Emotional state of patients in radiotherapy and how they deal with their disorder. AB - PURPOSE: The aim of the study was to record patients' symptoms of anxiety, depression and post-traumatic stress, as well as their subjective experience of illness, with different forms of radiotherapy and for different indications. The question is to be answered of whether more invasive techniques such as stereotactic radiotherapy involve greater stress or whether the psychological stress instead tends to be caused by the underlying disorder itself. PATIENTS AND METHODS: Questionnaires were given to 240 patients after conventional radiotherapy for a malignant underlying disorder, to 80 with a benign disorder, and to 67 patients following stereotactic radiotherapy. The German version of the Hospital Anxiety and Depression Scale (HADS-D) was used to measure anxiety and depression; the Post-Traumatic Symptom Scale (PTSS-10) was used to measure symptoms related to post-traumatic stress disorder (PTSD), and there were questions about patients' subjective experience of radiotherapy. RESULTS: 28% of all patients scored in the pathologic or borderline anxiety range; 26% were in the pathologic or borderline depression range. 22% of patients were above the diagnostic cutoff for the PTSS-10. No differences were evident between the three groups in terms of anxiety and stress-related symptoms. Women were significantly (p = 0.001) more severely affected by symptoms of PTSD and anxiety than men. No gender differences could be proven in terms of depression. In the HADS-D, patients with a benign underlying disorder had significantly (p < 0.05) lower depression values than the two other groups studied. CONCLUSION: Patients who had undergone stereotactic radiotherapy did not demonstrate higher values for anxiety, depression or PTS symptoms than patients treated with conventional radiotherapy. From the results submitted here it cannot be assumed that this form of treatment leads to an increased incidence of traumatic stress or even post traumatic stress disorder (PTSD). All in all, it is the type of underlying disorder (malignant/benign), which affects the extent of psychological stress experienced by patients following radiotherapy. PMID- 20354662 TI - Nodal follicular lymphoma: the role of radiotherapy for stages I and II. AB - PURPOSE: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL). METHODS: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank. RESULTS: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively. The main cause of failure is out-of-field recurrence. In nonrandomized trials, IFI led to higher relapse rates, but larger irradiation volumes failed to show an impact on OS and were associated with increased toxicity. Additional chemotherapy mostly failed to improve treatment results achieved with RT alone. CONCLUSION: Since there is no evidence so far that the prognosis of stage I and II nodal FL can be improved by the use of EFI/TNI/TLI, IFI is recommended internationally. Adequate irradiation doses range between 25 30 Gy to subclinical disease and 36-40 Gy to involved sites. To further improve the curative potential of RT in early-stage FL, novel combined approaches (e.g., RT + immunotherapy with rituximab) are under investigation. PMID- 20354663 TI - Dose escalation in prostate radiotherapy up to 82 Gy using simultaneous integrated boost: direct comparison of acute and late toxicity with 3D-CRT 74 Gy and IMRT 78 Gy. AB - PURPOSE: To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radiotherapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82). PATIENTS AND METHODS: 94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale. RESULTS: Acute gastrointestinal toxicity >or= grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity >or= grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32) CONCLUSION: SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy. PMID- 20354664 TI - Treatment results of radiation therapy for muscle-invasive bladder cancer. AB - PURPOSE: To assess local control and survival rates in patients with muscle invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. PATIENTS AND METHODS: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. RESULTS: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. CONCLUSION: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. PMID- 20354665 TI - A new modification of combining vacuum therapy and brachytherapy in large subfascial soft -tissue sarcomas of the extremities. AB - PURPOSE: To present a modification of a technique combining the advantages of brachytherapy for local radiation treatment and vacuum therapy for wound conditioning after resection of subfascial soft-tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: Between January and May 2008, four patients with large (> 10 cm) subfascial STS of the thigh underwent marginal tumor excision followed by early postoperative HDR (high-dose-rate) brachytherapy (iridium-192) and vacuum therapy as part of their interdisciplinary treatment. The sponge of the vacuum system was used to stabilize brachytherapy applicators in parallel positions and to allow for a maximal wound contraction in the early postoperative phase, thus preventing seroma and deterioration of local dose distribution as optimized in computed tomography-(CT-)based three-dimensional conformal treatment planning. In three patients this was followed by external beam radiotherapy. Acute wound complications and late effects according to LENT SOMA after 4-8 months of follow-up were recorded. RESULTS: The combination of vacuum and brachytherapy was applicable in all patients. CT scans from the 1st postoperative day showed the shrinkage of the sponge located in the tumor bed with the brachytherapy applicators in the intended position and easily visible. 15-18 Gy in fractions of 3 Gy bid prescribed to 5 mm tissue depth were applied over the next days with removal of the sponge and applicators on days 5-8. No early or late toxicity exceeding grade 2 was observed. The mean Enneking Score for functional outcome was 63% (perfect function = 100%). CONCLUSION: The combination of vacuum and brachytherapy is applicable and safe in the treatment of large subfascial STS. PMID- 20354666 TI - [Demographic change: demands on the health care system and solutions using the example of Mecklenburg-Western Pomerania]. AB - The growing absolute number of the elderly causes an increase in the number of patients suffering from not only chronic diseases and multimorbidity, but also higher usage of the health care system. In the German Federal State of Mecklenburg-Western Pomerania (MW), the effects of demographic change will be more pronounced than in other regions. The objective of this article is to show the consequences of the changing population structure for the health care system. Using examples from MW, innovative models to secure high quality health care at the population level are presented. Examples include the establishment of subsidiary practices, multidisciplinary ambulatory health care centers, delegation models, ambulatory health care managers, telemedicine, and intensified and improved interdisciplinary networking. In the context of the demographic change, assisted care, adequate symptom control, maintaining personnel competence, preservation of an independent lifestyle with a high quality of life, and stimulation of social participation become priority objectives of medical care. Besides the effectiveness and the quality of results with regard to these objectives, innovative health care models should be economically evaluated at the population level under real life practice conditions. PMID- 20354667 TI - [Forecasts of morbidity based on population projections: what can health monitoring contribute?]. AB - It is assumed that an aging population will lead to an increase of incidence and prevalence rates of many diseases, thus, resulting in rising health care costs in Germany. Forecasts of morbidity will have to provide plausible information on probable trends of incidence and prevalence rates in order to derive measures to be taken within the health care system. These forecasts are based on population projections considering demographic change. Often, a simple methodical approach is applied by constantly extrapolating empirical morbidity rates into the future. This approach not only takes into account changes resulting from advanced medical care and prevention measures, but also improved health behavior among the population. The dimensions of these changes are still not known. Nevertheless, present trends, which could be utilized for developing dynamic scenarios of future processes, can be identified. For this, the health monitoring administrated by the Robert Koch Institute is a valuable data source. Using these data, morbidity rates and present trends regarding important diseases, which are not available from other data sources, can be determined. PMID- 20354668 TI - [The frequency of older people living in nursing homes: results from a population based study in Dortmund]. AB - Scientific studies often exclude institutionalized people. Thus, there is insufficient information about the percentage of older people, who are living in nursing homes. Furthermore, when they move to a care facility, it is questionable whether their new address is officially registered. This is a major prerequisite for their accessibility in studies. By using a standardized questionnaire, the number of nursing home residents in Dortmund was anonymously recorded. Their percentage of the population was determined separately for gender and age. This information was then compared to the official registry. Of those 65 years and older, 5.0% of women and 1.8% of men lived in long-term nursing homes. The percentage of institutionalized people of both genders increases with age; however, the correlation is stronger for women. Overall, 79.5% of the residents are female. To some extent, there were large differences between the information from the care facilities and the official registry concerning the number of residents. PMID- 20354669 TI - [Demographic change and the need for prioritization in health care: position of the German Medical Association]. AB - The German health care system will face major challenges in the near future. Progress in medicine as well as demographic change will combine to drastically exacerbate the scarcity of resources in the health care system. The word scarcity in this case not only refers to the availability of funds. Other resources, e.g., staff, attention, time, and organs for transplantation, are also becoming scarce. It is conceivable that, in the future, it will no longer be possible to provide medical services for all patients to the same extent as in the past. If the necessary resources are not available in the health care system, if the potential for saving resources has been more or less exhausted, and if rationing shall not be an option, the only option to resort to will be prioritization. Prioritization in the health care sector denotes a supply of services according to specific, predetermined criteria. A broad and open public debate, which would have to be accompanied as well as moderated by the Health Council ("Gesundheitsrat"), is essential for determining such criteria. PMID- 20354670 TI - [Theories on aging and health: what do aging and old age mean and what constitutes a good life in old age?]. AB - The present paper starts by introducing different perspectives of the aging process and includes biological, psychological, and sociological theories in its scope. The article addresses the issue of when "old age" begins and why a distinction is made between the third and fourth age. With increasing age, it becomes more and more difficult to differentiate between health-related losses due to illnesses or to aging. However, this can be important with respect to health behavior and health care. Having the best possible health in old age is an important factor for a good life in old age. Over their whole lives, from childhood to old age, people can actively contribute to their health in old age. But health is not the sole criterion for a good life in old age. Having interests and aims are just as important as being integrated in a social network. In old age, people often differ greatly and this is why there is such variety in what people consider to constitute a good life for themselves in old age. PMID- 20354671 TI - [Assistance systems for the elderly: the SmartSenior project]. AB - Demographic change is posing an enormous challenge for societies in industrialized countries: the number of elderly and chronically ill is on the rise, whereas the number of people in the work force is declining. Assistive technology can be an important factor in this process and will help to alleviate shortcomings of the present system. The following example of the joint research program "SmartSenior", which began in mid 2009, shows the stakeholders, challenges, and future trends of assistive technology for the elderly. There is potential for the application of modern technology in three areas: in the training of senior citizens' abilities and skills, in supporting the activities of daily life, and in the continuous monitoring of vital functions. PMID- 20354672 TI - [Demographic change as a chance for the health care industry]. AB - Further demographic change in Germany is "preprogrammed". With the increasing number of older people, the range of illnesses within the population will shift, thus, resulting in an increased number of multimorbid persons. From these two developments, a further increase in the demand for medical supplies and health services is expected. Thereby, diverse opportunities for healthcare management are associated with the creation of a health-related supply of goods and services taking into account the effects of demographic change. As measured by the number of employees, health care is already the largest economic branch in Germany. For health care workers, a number of opportunities are associated with qualification and professionalization as well as increased cooperation of occupational groups and multidisciplinary work by the changing demands in health care and nursing care of the aging population. Particularly personal or household-related services in the care of old and sick people harbor the potential for more employment. PMID- 20354673 TI - [Single-port technique in laparoscopic surgery]. AB - Laparoscopic operations using only one trocar (single-port technique) have the aim to further minimize the trauma of access incisions similar to NOTES. To carry this out special trocars and instruments are needed which are presented in this article with respect to application and function. The range of indications corresponds to the conventional laparoscopic surgery. Recent publications have shown that operations using a single-port technique are safe and efficient. Greater technical difficulties and higher costs must be considered. For the identification of significant advantages, randomized studies are still lacking. PMID- 20354674 TI - [Transsigmoid access for NOTES]. AB - Transsigmoidal access for NOTES operations is not limited by gender and offers an outstanding controllability of the entry point. Practically all anatomical regions of the abdomen are easily accessible. However, it is particularly prone to contamination and leakage and insufficiency of the access mean that it is far more prone to complications than using alternative access points. Currently, only few data are available on the results of animal experiments and differing technical approaches have been employed. Dedicated surgical instruments are required which should be modified according to the well proven transanal endoscopic microsurgery (TEM) set of instruments. In addition, specialized instrumentation (overtubes/trocars) and the use of transanal ultrasound seem to be recommendable. PMID- 20354675 TI - The integument of Psittacosaurus from Liaoning Province, China: taphonomy, epidermal patterns and color of a ceratopsian dinosaur. AB - Preserved skin of small dinosaurs is rare. Here, a specimen of the ceratopsian dinosaur, Psittacosaurus, presents some of the best preserved epidermal scales observed to date in a relatively small dinosaur, over wide areas extending from the head to the tail. We study the preserved epidermis of SMF R 4970, the different types of scales, color, and patterns, and their respective locations in the body. We use modern application of high-power digital imaging for close-up analysis of the tubercles and fragments of preserved color. Three types of scales are preserved, large plate-like scales, smaller polygonal scales or tubercles, and round pebble-like scales. The sizes of the plate-like scales vary in different parts of the body and vanish altogether posteriorly. Light and dark cryptic patterns are created by the associations of the tubercle and plate-like scales, and there is also evidence of countershading in the proximal caudal region, the body darker dorsally and lighter ventrally. Perhaps most impressive are the distinctive pigmented impressions of scales over most of the skeletal elements. The pigmentation follows the curvature of the bones implying that when it was deposited, the skin was still pliable and able to wrap around the visible parts of the elements. The present record of color is the first in a non-theropod dinosaur and only the second record in a non-avian dinosaur. Because of its resistance to degradation and ability to produce various color tones from yellows to blacks, we suggest that melanin was the dominant chemical involved in the coloration of Psittacosaurus. The data here enable us to reconstruct the colors of Psittacosaurus as predominantly black and amber/brown, in cryptic patterns, somewhat dull, but useful to a prey animal. Indeed, skin pigment within a partially degraded bone indicates that Psittacosaurus was scavenged shortly after death. The theropod dinosaur Sinosauropteryx has recently been reported to have naturally pigmented integumental structures, which the authors interpret as proof that they are protofeathers and not support fibers of collagen. Our findings in Psittacosaurus, on the other hand, indicate a more parsimonious and less profound alternative explanation, i.e., decomposition of the skin releases pigments that readily permeate underlying structures. PMID- 20354676 TI - Psychoses, PTSD, and depression in Somali refugees in Minnesota. AB - INTRODUCTION: Initial clinical observation of Somali patients seen at a busy inner-city community clinic (CUHCC) suggested that, in addition to the expected pictures of Posttraumatic Stress Disorder (PTSD) and depression previously seen in the clinic's Southeast Asian refugee population from 1980 to 2000, there was an unusually high number of young Somali men presenting with acute psychotic disturbances. OBJECTIVES: The aim of this study of health care utilization of Somali refugees (N = 600) seen in the mental health unit of the clinic from 2001 to 2009 was to investigate the major patterns of psychiatric disorders in this outpatient population and compare these findings with a cohort of non-Somali patients (N = 3,009) seen at the same outpatient clinic during the years 2007 2009. If the results supported the initial clinical observations that the rate of psychoses was higher among young Somali men than non-Somali men attending CUHCC clinic, then several areas of further research would recommend itself. First, since this study was not a study of prevalence of mental illness in the Somali community, the next step would be to undertake a study of community prevalence of mental illness among different age and gender cohorts. Second, further research should look into likely causative and contributory risk factors to explain the development of psychoses among Somali young men. METHODS: Somali and non-Somali patients were diagnosed according to DSM-IV-R criteria. Main outcome measures (diagnoses, age cohort, sex) were analyzed by Chi-square tests. Patterns of illness and adjustment varied significantly by age and gender cohorts, reflecting the relevance of age and gender at time of trauma on different trauma and loss experiences and cultural and religious shaping of subsequent adjustment and symptoms. RESULTS: The study confirmed that almost half of the Somali male patients are under age 30, 80% of whom presented with psychoses, compared with the rate of psychosis (13.7%) in the non-Somali control group of same-aged males at the clinic. The older male, and the majority of Somali female patients, show predominantly depressive and PTSD symptomatology. CONCLUSIONS: War trauma experienced in childhood, early malnutrition from famines, head trauma, and excess Khat use in male adolescents provide partial explanations for the large number of young psychotic Somali men seen in the clinic from 2001 to 2009. PMID- 20354677 TI - The impact of psychopathy on violence among the household population of Great Britain. AB - BACKGROUND: The public health impact of psychopathy on violence has not previously been measured in the general population. METHODS: Psychopathy was measured using the Psychopathy Checklist:Screening Version (PCL:SV) in adults 16 74 years (n = 638) in households in England, Scotland and Wales in a two-phase survey which included self-reported measures of violence. RESULTS: Participants with PCL:SV scores 11 or above demonstrated a prevalence of 2.1% (95% CI 1.2, 3.8) but accounted for 18.7% of violent incidents, a population-attributable risk of 16.6%, and demonstrated an exponential rise in reported violent incidents. Psychopathic traits correlated with victim injury, multiple victim subtypes and locations. CONCLUSIONS: Psychopathy makes a substantial impact on violence among the general population despite a low prevalence. Explanations of this association include interpersonal difficulties due to psychopathic traits, fearlessness, thrill seeking, and antisocial lifestyle, but not impulsivity independent of antisocial lifestyle. PMID- 20354678 TI - Symptomatic urinary tract infections after surgery for prolapse and/or incontinence. AB - INTRODUCTION AND HYPOTHESIS: The purpose of our study was to estimate the frequency and risk factors for symptomatic urinary tract infection (UTI) after surgery for stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP). METHODS: Case-control study of 389 consecutive women who underwent surgery for POP and/or SUI. Cases were defined as a symptomatic, culture-confirmed UTI within 6 weeks of surgery. Multivariable logistic regression was used to determine independent risk factors. RESULTS: Thirty five (9%) women developed a UTI. The risk of UTI was significantly increased by previous history of multiple UTIs (adjusted OR: 3.7, CI 1.4-10.1), increased distance between the urethra and the anus (adjusted OR: 1.4, CI 1.1-1.9), and prolonged duration of catheterization (adjusted odds ratio (OR) for >or=10 days: 4.2, 95% CI 1.5-11.6); 94.6% of catheterizing women were prescribed daily nitrofurantoin. CONCLUSIONS: UTI is an important postoperative morbidity after urogynecologic surgery and is common in catheterizing women despite antibiotic prophylaxis. PMID- 20354679 TI - Effects of glyceollin I on vascular contraction in rat aorta. AB - The present study was undertaken to investigate the molecular mechanisms by which glyceollin I inhibits vascular contraction in rat aorta. Rat aortic rings were treated with either glyceollin I or vehicle when vascular contraction reached plateaus. We measured the activity of GTP-RhoA and Rho GTPase-activating protein (RhoGAP) and the phosphorylation level of the myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1), and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). Glyceollin I reduced vascular contraction whether endothelium is present or denuded. Glyceollin I reduced vascular contraction induced by NaF, U46619, phenylephrine, or PDBu. Blockers of K(+) channels did not affect the vasorelaxation induced by glyceollin I. Glyceollin I reduced activation of RhoA as well as phosphorylation level of MLC(20). Glyceollin I also reduced phosphorylation of MYPT1 and CPI17 induced by NaF but not PDBu. However, glyceollin I had no direct effect on RhoGAP activation in vitro. Glyceollin I reduced vascular contraction, at least in part, through inhibition of the RhoA/Rho-kinase signaling pathway. PMID- 20354681 TI - New approaches to the study of human brain networks underlying spatial attention and related processes. AB - Cognitive processes, such as spatial attention, are thought to rely on extended networks in the human brain. Both clinical data from lesioned patients and fMRI data acquired when healthy subjects perform particular cognitive tasks typically implicate a wide expanse of potentially contributing areas, rather than just a single brain area. Conversely, evidence from more targeted interventions, such as transcranial magnetic stimulation (TMS) or invasive microstimulation of the brain, or selective study of patients with highly focal brain damage, can sometimes indicate that a single brain area may make a key contribution to a particular cognitive process. But this in turn raises questions about how such a brain area may interface with other interconnected areas within a more extended network to support cognitive processes. Here, we provide a brief overview of new approaches that seek to characterise the causal role of particular brain areas within networks of several interacting areas, by measuring the effects of manipulations for a targeted area on function in remote interconnected areas. In human participants, these approaches include concurrent TMS-fMRI and TMS-EEG, as well as combination of the focal lesion method in selected patients with fMRI and/or EEG measures of the functional impact from the lesion on interconnected intact brain areas. Such approaches shed new light on how frontal cortex and parietal cortex modulate sensory areas in the service of attention and cognition, for the normal and damaged human brain. PMID- 20354680 TI - Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents. AB - RATIONALE: Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. OBJECTIVES: This study represents a systematic examination of this hypothesis. METHODS: Salvinorin A was isolated from S. divinorum and was evaluated in a battery of in vitro and in vivo procedures designed to detect cannabinoid activity, including CB(1) receptor radioligand and [(35)S]GTPgammaS binding, calcium flux assay, in vivo cannabinoid screening tests, and drug discrimination. RESULTS: Salvinorin A did not bind to nor activate CB(1) receptors. In vivo salvinorin A produced pronounced hypolocomotion and antinociception (and to a lesser extent, hypothermia). These effects were blocked by the selective KOR antagonist, JDTic, but not by the CB(1) receptor antagonist rimonabant. Interestingly, however, rimonabant attenuated KOR activation stimulated by U69,593 in a [(35)S]GTPgammaS assay. Salvinorin A did not substitute for Delta(9)-tetrahydrocannabinol (THC) in mice trained to discriminate THC. CONCLUSIONS: These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvinorin A on the endocannabinoid system. Further, the results suggest that rimonabant reversal of salvinorin A effects in previous studies may be explained in part by rimonabant attenuation of KOR activation. PMID- 20354682 TI - Autocrine/paracrine action of vitamin D on FGF23 expression in cultured rat osteoblasts. AB - To explore the local mechanisms of fibroblast growth factor (FGF) 23 regulations, we examined the FGF23 expression patterns in an osteoblast culture model. The characteristics of cultured rat calvaria osteoblasts in half-confluence, confluence, osteoid deposition, and osteoid mineralization stages might reflect the proliferation, differentiation, maturation, and matrix mineralization stages, respectively. Compared with proliferating cells in half-confluence, FGF23 expression was upregulated by 7.5-fold at the mRNA level and 126% at the protein level in confluent differentiated cells as determined by real-time RT-PCR and Western blot analysis. Interestingly, mRNA levels of CYP27B1 (the gene coding for 1alpha-hydroxylase enzyme which catalyses the conversion of 1alpha,25 dihydroxyvitamin D, 1alpha,25[OH]2D, from its inactive form, 25 hydroxycholecalciferol, 25[OH]D) and CYP24A (the gene coding for 24-hydroxylase, a target gene of 1alpha,25[OH]2D) were significantly increased by twofold and 34 fold, respectively, in differentiated osteoblasts compared with proliferating cells. We next examined if the local production of 1alpha,25(OH)2D might contribute to the FGF23 upregulation. We cultured osteoblasts in serum-free medium with or without 25-(OH)D (the substrate of 1alpha-hydroxylase). FGF23 mRNA levels were increased in proliferating cells (16-fold) and in differentiated cells (28-fold) by the physiological dose of 25-(OH)D3 treatment. CYP27B1 was slightly but significantly upregulated and CYP24A was increased by 1,700-fold and 800-fold, respectively, in transcriptional levels. Because FGF23 was upregulated in confluent osteoblasts regardless of the presence or absence of 25-(OH)D in serum-free medium, we further examined the possible impact of cell communication on FGF23 expression. We treated osteoblasts with carbenoxolone, a gap junction Cx43 blocker in serum-free medium. The FGF23 mRNA level was reduced by 50% in confluent differentiated cells and slightly but not significantly reduced in half confluent cells by carbenoxolone treatments. The results suggested that upregulation of FGF23 in differentiated osteoblast appeared to be due to increased autocrine/paracrine action of osteoblast-derived 1alpha,25(OH)2D and increased cell communication, which were identified in cultured rat calvaria osteoblasts. These results indicate that FGF23 expression was stimulated not only by circulating calcitriol but also by locally produced 1alpha,25(OH)2D. The local mechanisms of FGF23 expression remain to be characterized. PMID- 20354684 TI - The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone increases bone resorption in women with type 2 diabetes: a randomized, controlled trial. AB - In previous studies, with up to 16 weeks of exposure to rosiglitazone or pioglitazone, circulating markers of bone formation [procollagen I N-terminal propeptide (P1NP), osteocalcin, and bone-specific alkaline phosphatase] decreased but no change in bone resorption markers was found. We examined the effect of rosiglitazone on bone resorption and formation markers when used for 24 weeks. This post-hoc analysis of a double-blind, placebo-controlled, randomized trial evaluated the effects of 6 months of rosiglitazone use versus placebo on circulating markers of bone turnover in 111 patients with type 2 diabetes and cardiovascular disease or additional cardiac risk factors. The principal end points for analysis were changes in bone formation and resorption markers, measured by P1NP and carboxy-terminal cross-links (CTX), respectively. There were 111 subjects who completed the study and had baseline and 6-month data; mean age was 56, including 41% women and 67% nonwhite (50 black, 18 Hispanic, and six other), and subjects were evenly distributed between placebo and rosiglitazone groups. Women treated with rosiglitazone had higher CTX levels (0.43 ng/mL) than those who received placebo (0.23 ng/mL) (P = 0.007), with no significant differences in P1NP or OPG. Overall, in stratified analyses of men and in stratified analyses among different ethnicities, there were no statistically significant differences observed in CTX, P1NP, OPG, PTH, or 25-OHD between the treatment groups. Women taking rosiglitazone had higher circulating markers of bone resorption, which is contrary to prior studies of shorter duration, where the principal observation was a decrease in markers of bone formation. PMID- 20354683 TI - Application of structural rigidity analysis to assess fidelity of healed fractures in rat femurs with critical defects. AB - Approximately 6 million fractures occur each year in the United States, with an estimated medical and loss of productivity cost of $99 billion. As our population ages, it can only be expected that these numbers will continue to rise. While there have been recent advances in available treatments for fractures, assessment of the healing process remains a subjective process. This study aims to demonstrate the use of micro-computed tomography (microCT)-based structural rigidity analysis to accurately and quantitatively assess the progression of fracture healing over time in a rat model. The femora of rats with simulated lytic defects were injected with human BMP-2 cDNA at various time points postinjury (t = 0, 1, 5, 10 days) to accelerate fracture healing, harvested 56 days from time of injury, and subjected to microCT imaging to obtain cross sectional data that were used to compute torsional rigidity. The specimens then underwent torsional testing to failure using a previously described pure torsional testing system. Strong correlations were found between measured torsional rigidity and computed torsional rigidity as calculated from both average (R2 = 0.63) and minimum (R2 = 0.81) structural rigidity data. While both methods were well correlated across the entire data range, minimum torsional rigidity was a better descriptor of bone strength, as seen by a higher Pearson coefficient and smaller y-intercept. These findings suggest considerable promise in the use of structural rigidity analysis of microCT data to accurately and quantitatively measure fracture-healing progression. PMID- 20354685 TI - Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men. AB - Cardiovascular disease and osteoporosis are thought to share common risk factors, and metabolic syndrome (MS) is composed of major risk factors for cardiovascular disease. This study was performed to investigate the relationships between specific MS components and bone mineral density (BMD). BMD was measured at the femoral neck of Korean men aged 40 years or more (n = 1,780) and postmenopausal women (n = 1,108) using dual-energy X-ray absorptiometry. We identified subjects with MS as defined by two criteria, International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). Body fat and lean mass were measured via bioimpedance analysis. The prevalence of MS was 19.8% and 7.7% in men and 20.8% and 11.6% in postmenopausal women according to the AHA/NHLBI definition and the IDF definition, respectively. After multivariate adjustment, femoral neck BMD was significantly lower in subjects with MS regardless of diagnostic criteria. BMD decreased as the number of MS components increased (P < 0.001 for trends in both sexes). Among MS components, waist circumference was the most important factor in this negative association. When multiple linear regression models were applied to each 5-kg weight stratum to test for a linear trend, waist circumference and fat mass were negatively associated with BMD and lean mass was positively associated with BMD in men but not in women. MS was associated with a lower BMD in Korean men and postmenopausal women, suggesting that visceral fat may lead to bone loss, especially in men. PMID- 20354686 TI - Increased frequency of CYP2C9 variant alleles and homozygous VKORC1*2B carriers in warfarin-treated patients with excessive INR response. AB - BACKGROUND: Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced warfarin dose requirement and an increased risk of bleeding with warfarin treatment, but the implementation of genotyping as routine practice is still controversial. The objective of this study was to investigate whether the frequencies of CYP2C9 variant alleles (*2 and *3), and VKORC1 haplotypes (*2A/B) were increased in a population of warfarin-treated patients with an excessive INR response. METHODS: All patients with INR values >5 detected by routine monitoring at Diakonhjemmet Hospital, Oslo, Norway, between October 2006 and January 2009 were prospectively enrolled in the study (n = 131, 'cases'). A group of patients with normal INR values (2-3) were randomly included as the reference population (n = 130, 'controls'). The frequencies of CYP2C9 variant alleles *2 (430C > T) and *3 (1075A > C), VKORC1 haplotypes *2A (1173G > T) and *2B (1173G > T + 497T >G), and the respective genotypes were compared between the study groups by chi square tests [odds ratio (OR) of cases vs. controls with 95% confidence intervals (CI) calculated for the various end-points]. RESULTS: About two thirds of the patients in the high INR group were in the maintenance phase of the treatment (>3 weeks from first warfarin dose to measurement of INR >5). The frequency of CYP2C9 variant alleles (sum of *2 and *3) was significantly higher in patients with high INR cases than in the controls (OR 1.6, 95% CI 1.03-2.52; p = 0.036). Observed frequencies for each of the variant alleles were also higher in the cases than in the controls (i.e., 2C9*3: OR 1.97, 95% CI 0.91-2.41, p = 0.073; 2C9*2: OR 1.36, 95% CI 0.88-1.58, p = 0.246). There were no significant differences in VKORC1*2 haplotype frequencies between the two subgroups, but the number of homozygous VKORC1*2B carriers was significantly higher in cases than in controls (OR 2.72, 1.02-7.24; p = 0.039). CONCLUSION: The presence of CYP2C9 variant alleles and the homozygous VKORC1*2B genotype was associated with elevated INR values in warfarin treated patients. These results support the implementation of genotyping as a tool to identify patients with an increased risk of excessive anticoagulation during warfarin treatment. PMID- 20354687 TI - Explaining variability in ciclosporin exposure in adult kidney transplant recipients. AB - PURPOSE: Optimal ciclosporin A (CsA) exposure in kidney transplant recipients is difficult to attain because of variability in CsA pharmacokinetics. A better understanding of the variability in CsA exposure could be a good means of individualizing therapy. Specifically, genetic variability in genes involved in CsA metabolism could explain exposure differences. Therefore, this study is aimed at identifying a relationship between genetic polymorphisms and the variability in CsA exposure, while accounting for non-genetic sources of variability. METHODS: De novo kidney transplant patients (n = 33) were treated with CsA for 1 year and extensive blood sampling was performed on multiple occasions throughout the year. The effects of the non-genetic covariates hematocrit, serum albumin concentration, cholesterol, demographics (i.e., body weight), CsA dose interval, prednisolone dose and genetic polymorphisms in genes encoding ABCB1, CYP3A4, CYP3A5, and PXR on CsA pharmacokinetics were studied using non-linear mixed effect modeling. RESULTS: The pharmacokinetics of CsA were described by a two compartment disposition model with delayed absorption. Body weight was identified as the most important covariate and explained 35% of the random inter-individual variability in CsA clearance. Moreover, concurrent prednisolone use at a dosage of 20 mg/day or higher was associated with a 22% higher clearance of CsA, hence lower CsA exposure. In contrast, no considerable genotype effects (i.e., greater than 30-50%) on CsA clearance were found for the selected genes. CONCLUSIONS: It appears that the selected genetic markers explain variability in CsA exposure insufficiently to be of clinical relevance. Therefore, therapeutic drug monitoring is still required to optimize CsA exposure after administration of individualized doses based on body weight and, as this study suggests, co administration of prednisolone. PMID- 20354688 TI - Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadol's O-demethylation via CYP2D6. AB - PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received placebo, 10, 20, 30, and 50 mg paroxetine as single oral doses at bedtime. Next morning the pupil was measured followed by oral intake of 50 mg of tramadol, and urine was collected for 8 h. Three hours after ingestion of tramadol a second measurement of the pupil was performed. Enantioselective urine concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P < 0.001). Likewise, a reduction in the relative constriction amplitude with a geometric mean difference of 0.81 (95% CI 0.71 0.92) (P < 0.001) was seen. A dose-dependent inhibition of the metabolism of tramadol by an increase in the two urinary metabolic ratios (+)-tramadol / (+)-M1 [geometric mean difference 9.09, 95% CI 5.60-14.73 (P < 0.001)] and (-)-M1 / (+) M1 [geometric mean difference 2.84, 95% CI 2.15-3.77 (P < 0.001)] was also observed. CONCLUSIONS: Paroxetine is a dose-dependent dilator of the pupil and as expected a dose-dependent inhibitor of (+)-tramadol's O-demethylation. PMID- 20354689 TI - Melamine nephropathy. PMID- 20354690 TI - Specific management of acute renal failure caused by an upper ureteral stone in a solitary pelvic kidney. AB - A 36-year-old man presented with left lumbosacral region pain and 2 days of oliguria. Acute renal failure of a solitary pelvic kidney was diagnosed after a blood creatinine test, color Doppler ultrasonography, and magnetic resonance imaging. The cause of the acute renal failure was not clear; however, acute ureteral obstruction was presumed and emergency surgery was performed. The unusual anatomy of the kidney required specific management to find and relieve the cause of the obstruction. We found and cleared an upper ureteral stone by endoscopic surgery after exploring the kidney through open surgery. PMID- 20354691 TI - Superstatistics analysis of the ion current distribution function: Met3PbCl influence study. AB - A novel analysis of ion current time series is proposed. It is shown that higher (second, third and fourth) statistical moments of the ion current probability distribution function (PDF) can yield new information about ion channel properties. The method is illustrated on a two-state model where the PDF of the compound states are given by normal distributions. The proposed method was applied to the analysis of the SV cation channels of vacuolar membrane of Beta vulgaris and the influence of trimethyllead chloride (Met(3)PbCl) on the ion current probability distribution. Ion currents were measured by patch-clamp technique. It was shown that Met(3)PbCl influences the variance of the open-state ion current but does not alter the PDF of the closed-state ion current. Incorporation of higher statistical moments into the standard investigation of ion channel properties is proposed. PMID- 20354692 TI - Occurrence, fate, and biodegradation of estrogens in sewage and manure. AB - The estrogens estrone (E1), 17alpha-estradiol (E2alpha), 17beta-estradiol (E2beta), and estriol (E3) are natural sex hormones produced by humans and animals. In addition, there are some synthetic estrogens, such as 17alpha ethinylestradiol (EE2), used for contraception purposes. These compounds are able to produce endocrine disruption in living organisms at nanogram-per-liter levels. In both humans and animals, estrogens are excreted in urine and feces, reaching the natural environment through discharge from sewage treatment plants (STP) and manure disposal units. In STPs, hormone removal depends on the type of treatment process and on different parameters such as the hydraulic and sludge retention times. Thus, hormone elimination rates vary from 0% to 90% in different STPs. Animals are also an important source of estrogens in the environment. Indeed, animals produce high concentrations of hormones which will end up in manure which is typically spread on land. Hence, waste-borne animal hormones may transfer these pollutants to the soil. The purpose of this review is to highlight the significance for both health and the environment of pollution by estrogens and critically review the existing knowledge on their fate and removal in different treatment processes. Relevant information on the microbial degradation of hormones and metabolic pathways is also included. PMID- 20354693 TI - Cellulase production by Aspergillus niger in biofilm, solid-state, and submerged fermentations. AB - Cellulase production by Aspergillus niger was compared in three different culture systems: biofilm, solid-state, and submerged fermentation. Biofilm and solid state fermentations were carried out on perlite as inert support, and lactose was used as a carbon source in the three culture systems. In cryo-scanning electron microscopy, biofilm and solid-state cultures gave similar morphological patterns and confirmed that both spore first attachment and hyphal adhered growth are helped by the production of an adhesive extracellular matrix. Biofilm cultures produced higher cellulase activities than those in submerged and solid-state cultures (1,768, 1,165, and 1,174 U l(-1), respectively). Although biofilm cultures grew less than the other cultures, they produced significantly higher cellulase yields (370, 212, and 217 U g(-1) lactose, respectively) and volumetric productivities (24, 16, and 16 U l(-1) h(-1), respectively). Likewise, endoglucanase and xylanase activities were higher in biofilm cultures. Under the conditions tested, it seems that fungal attached growth on perlite may favor better enzyme production. Biofilms are efficient systems for cellulase production and may replace solid-state fermentation. Biofilm fermentation holds promise for further optimization and development. The results of this work reveal that fungal biofilms may be used for the commercial production of cellulase employing the technology developed for submerged fermentation at high cell densities. PMID- 20354694 TI - Occurrence, production, and export of lipophilic compounds by hydrocarbonoclastic marine bacteria and their potential use to produce bulk chemicals from hydrocarbons. AB - Petroleum (or crude oil) is a complex mixture of hydrocarbons. Annually, millions of tons of crude petroleum oil enter the marine environment from either natural or anthropogenic sources. Hydrocarbon-degrading bacteria (HDB) are able to assimilate and metabolize hydrocarbons present in petroleum. Crude oil pollution constitutes a temporary condition of carbon excess coupled to a limited availability of nitrogen that prompts marine oil-degrading bacteria to accumulate storage compounds. Storage lipid compounds such as polyhydroxyalkanoates (PHAs), triacylglycerols (TAGs), or wax esters (WEs) constitute the main accumulated lipophilic substances by bacteria under such unbalanced growth conditions. The importance of these compounds as end-products or precursors to produce interesting biotechnologically relevant chemicals has already been recognized. In this review, we analyze the occurrence and accumulation of lipid storage in marine hydrocarbonoclastic bacteria. We further discuss briefly the production and export of lipophilic compounds by bacteria belonging to the Alcanivorax genus, which became a model strain of an unusual group of obligate hydrocarbonoclastic bacteria (OHCB) and discuss the possibility to produce neutral lipids using A. borkumensis SK2. PMID- 20354695 TI - Silicone-based scar therapy: a review of the literature. AB - Hypertrophic and keloid scars still are among the banes of plastic surgery. In the treatment arsenal at the disposal of the plastic surgeon, topical silicone therapy usually is considered the first line of treatment or as an adjuvant to other treatment methods. Yet, knowledge concerning its mechanisms of action, clinical efficacy, and possible adverse effects is rather obscure and sometimes conflicting. This review briefly summarizes the existing literature regarding the silicone elastomer's mechanism of action on scars, the clinical trials regarding its efficacy, a description of some controversial points and contradicting evidence, and possible adverse effects of this treatment method. Topical silicone therapy probably will continue to be the preferred first-line treatment for hypertrophic scars due to its availability, price, ease of application, lack of serious adverse effects, and relative efficacy. Hopefully, future randomized clinical trials will help to clarify its exact clinical efficacy and appropriate treatment protocols to optimize treatment results. PMID- 20354696 TI - How texture-inducing contraction vectors affect the fibrous capsule shrinkage around breasts implants? AB - BACKGROUND: Breast augmentation was performed on nine female volunteer patients to determine the influence of three textured surfaces on fibrous capsule formation. The high degree of surface texture reduced the capsular fibrous tissue formation. METHODS: Patients were distributed according to the degree of texture created by the open-pore diameter and depth of the surface texture. Macroscopic and histological examinations were performed to evaluate the implant texture and fibrous capsule interface. Magnetic resonance imaging established a mutual correlation with breast firmness achieved by the Baker grade. RESULTS: The parallelogram law was applied to linear vectors arising from the same initial point into the concavities or undulations on the textured surface to achieve the resultant contraction vector. They were identical to resultant vectors created on the fibrous capsule except in the inverted direction. The adhesive effect or mirror-image tissue response to the implant texture on the fibrous capsule noticeably reduced capsular contracture but only with macrotextured implants. Increased capsular contracture resulted from implants showing micro- and medium surface texture with no significant difference between them. CONCLUSION: BiocellTM implants created resultant vectors on the capsular interface of small and similar lengths with divergent directions creating natural breast firmness. Biodegradation of PolyurethaneTM foam disrupted the texture from creating resultant vectors of long and different lengths and in variable directions, increasing breast firmness from 12 months. SiltexTM implants created few and very long resultant vectors perpendicular to the fibrous capsule that developed fibrous capsule contraction after 9 months. We conclude that implants with macrotextured surfaces significantly reduced the risk of fibrous capsular contraction. PMID- 20354697 TI - The bivectorial full-thickness superiorly based NAC flap: a new option to increase plasticity and decrease tension in the superior pedicle vertical mammaplasty technique. PMID- 20354699 TI - Laparoscopic exploration of the common bile duct with a rigid scope in patients with problematic choledocholithiasis. AB - BACKGROUND: The development of laparoscopic cholecystectomy as a minimally invasive approach to eliminate gallstones, in conjunction with increasingly sophisticated techniques for removal of common bile duct (CBD) stones by endoscopic sphincterotomy, has revolutionized the treatment of choledocholithiasis. We describe a new technical approach to laparoscopic exploration of the CBD after unsuccessful endoscopic stone extraction. METHODS: Eleven patients were subjected to laparoscopic exploration of the CBD with choledochotomy using a rigid scope (24-Fr nephroscope) during the last 2 years. Of these patients, 10 had unsuccessful preoperative (7 cases) or intraoperative (3 cases) stone extraction, and 1 case had a single impacted stone 2.3 cm in diameter. Five patients had a single bile duct stone and 6 patients had multiple stones. The size of the stones ranged from 9.5 to 24 mm (mean = 12.6 +/- 4 mm). RESULTS: Balloon dilation of the papilla of Vater was done in all patients. Most of the stones were fractured and pushed into the duodenum with rigid grasping forceps but a lithotripter was required in 2 patients. Stone clearance was 100%; complications related to the procedure were not observed. After CBD clearance, primary closure of the choledochotomy was achieved in 10 patients. In 1 patient who had CBD perforation during a previous procedure, choledochotomy was closed over a T-tube. The mean operative time was 124 +/- 26.7 min (range = 84-165 min) and the mean postoperative hospital stay was 4 +/- 1.7 days (range = 3-7 days). CONCLUSIONS: Laparoscopic exploration of the CBD with a rigid scope is an efficacious procedure in dealing with unsuccessful endoscopic stone extraction. PMID- 20354700 TI - Dual anterior interventricular artery type IV: a rare anatomical variation. AB - Type IV dual anterior interventricular artery (AIVA) is a rare variant that involves bilateral connection of this vessel to the left main coronary artery and right coronary artery or right aortic sinus. We present a case of such a variant where the ectopic branch traveled an intraseptal course, i.e., through the superior aspect of the crista supraventricularis in a subendocardial position and then intramyocardially inside the upper interventricular septum to reach the anterior interventricular sulcus and descend toward the apex. In a left anterior oblique view, this course lacked the typical caudal anterior loop but it was recognized by virtue of emergence of a septal branch as the first branch of the ectopic AIVA. Recognition of this variant and differentiation among the possible courses of the ectopic branch is important for patient management. PMID- 20354701 TI - A phase I/II study of oxaliplatin and paclitaxel in patients with non-resectable cancer of the oesophagus and adenocarcinoma of the gastro-oesophageal junction: a study of the Arbeitsgemeinschaft Internistische Onkologie. AB - PURPOSE: To assess the efficacy and toxicity of paclitaxel and oxaliplatin in patients with non-resectable cancer of the oesophagus and adenocarcinoma of the gastro-oesophageal junction. METHODS: Treatment consisted of oxaliplatin 85 mg/m(2) and paclitaxel 90 mg/m(2) on days 1, 15 and 29 every 6 weeks. Patients with a non-resectable cancer of the oesophagus and/or adenocarcinoma of the gastro-oesophageal junction were eligible. RESULTS: Twenty-six chemotherapy-naive patients were enrolled who had the following characteristics: median age 59.5 years (range 46-81); ECOG scores of 0/1/2 for 7/16/3 patients, respectively, and 23 (88%) patients had metastatic disease. There were 5 patients (19%) with adenocarcinoma of the gastro-oesophageal junction and 21 patients (81%) with oesophageal cancer; 19 (73%) had a squamous cell cancer and 7 (27%) had an adenocarcinoma. NCI grade 4 toxicity (neutropenia) was observed in one patient. Non-haematological toxicity consisted mainly of grade 1/2 neurosensory toxicity. The overall response rate by the intention-to-treat analysis was 15% with 4 patients having confirmed partial response. Overall tumour control rate was 73%. Median overall survival was 12.3 months (range 1.5-66) and median time to progression was 4.5 months (range 0.8-19.3). CONCLUSION: This regimen is well tolerated and demonstrates a modest response rate with a favourable disease control rate. PMID- 20354702 TI - Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of beta-glucuronidase activity in intestinal lumen. AB - Irinotecan hydrochloride (CPT-11) is a useful drug for cancer chemotherapy but sometimes induces severe diarrhea clinically. CPT-11 is mainly activated to SN-38 by carboxylesterase (CES) and then detoxified to SN-38 glucuronide (SN-38G) by UDP-glucuronosyltransferase (UGT) in the liver. SN-38G is excreted via bile and de-conjugated to SN-38 by beta-glucuronidase (beta-GLU) in the intestinal content. In order to clarify the alleviative effect of antibiotics on CPT-11 induced diarrhea, we examined whether penicillin G and streptomycin (SM) alleviate CPT-11-induced delayed-onset diarrhea using three diarrheal models, i.e., Wistar rats with repeated dosing of CPT-11 (60 mg/kg/day i.v. for 4 consecutive days) and Wistar and Gunn rats with a single dosing of CPT-11 (200 and 20 mg/kg i.v., respectively). Gunn rats have an inherited deficiency of UGT1A and cannot conjugate SN-38 to SN-38G. Therefore, onset of CPT-11-induced diarrhea in Gunn rats is not affected by beta-GLU activity. SM alleviated diarrhea in all three diarrheal models. The alleviation of diarrhea by SM in Gunn rats indicated that the effect of SM occurred by a mechanism other than the inhibition of beta GLU activity. SM decreased CPT-11 and/or SN-38 concentrations in intestinal tissues and alleviated epithelial damage from the ileum to colon. SM did not inhibit beta-GLU activity in the cecal content. SM also inhibited the intestinal absorption of CPT-11 and decreased CES activity and increased UGT activity in the intestinal epithelium. These findings indicated that SM decreased the exposure of CPT-11 and SN-38 to the intestinal epithelium by inhibiting the absorption of CPT 11 from the intestinal lumen and the change of CES and UGT activities in the intestinal epithelium and alleviated delayed-onset diarrhea. PMID- 20354703 TI - [Dice test--a simple method for assessment of visual acuity in infants with visual deficits]. AB - PURPOSE: Determination of visual acuity in low vision infants or patients with additional cerebral retardation is difficult. In our low vision department we used dice of different sizes and colors as well as other defined objects to determine visual acuity (VA). In this study we compared the results of the dice test with conventional tests for measurement of visual acuity. METHODS: A total of 88 children with different causes of visual impairment e.g. albinism, retinal scars, retinopathy of prematurity (ROP), achromatopsia and optic atrophy etc., were included in this longitudinal study. Median follow-up time was 8.7 years (range 2.9-18.9 years). The first reliable examination was performed between the ages of 4 and 24 months (median 11 months). We estimated VA depending on the edge length of the dice, which were recognized at a distance of 30 cm, while 4 mm complied with VA 20/200. Best corrected binocular visual acuity was compared between the dice test, measurement with the Lea symbols and with numbers or Landolt rings. RESULTS: Estimation of visual acuity using the dice test was possible at the end of the first year of life (median 11 months, range 4-27 months). Although observation is limited to visual acuity results in the low vision range between light reaction and 20/120 there was nearly complete agreement between all three VA measurements. Visual acuity ranged from light perception to 20/20 with a median of 20/100. In 39 patients visual acuity was 20/200 or less at the end of the observation period. Visual acuity estimation overestimated visual acuity only in 5 out of the 88 patients, while in all of the patients with later acuity measurements better than 20/200, our best value of 20/200 was achieved. CONCLUSIONS: Using simple visual objects, such as dice with different colors and size down to an edge length of 4 mm, it is possible to estimate visual acuity in low vision infants within the first year of life. This option is also very helpful in patients who are not able to perform other visual acuity measurements or to give reliable answers using preferential looking, such as severely handicapped patients. In contrast to preferential looking with this dice test there is not only judgment of the reaction by the observer but also activity of the patient who grips the dice he can really see. This allows better counseling of families with low vision infants concerning current and later visual functions. PMID- 20354704 TI - Perch-hunting in insectivorous Rhinolophus bats is related to the high energy costs of manoeuvring in flight. AB - Foraging behaviour of bats is supposedly largely influenced by the high costs of flapping flight. Yet our understanding of flight energetics focuses mostly on continuous horizontal forward flight at intermediate speeds. Many bats, however, perform manoeuvring flights at suboptimal speeds when foraging. For example, members of the genus Rhinolophus hunt insects during short sallying flights from a perch. Such flights include many descents and ascents below minimum power speed and are therefore considered energetically more expensive than flying at intermediate speed. To test this idea, we quantified the energy costs of short manoeuvring flights (<2 min) using the Na-bicarbonate technique in two Rhinolophus species that differ in body mass but have similar wing shapes. First, we hypothesized that, similar to birds, energy costs of short flights should be higher than predicted by an equation derived for bats at intermediate speeds. Second, we predicted that R. mehelyi encounters higher flight costs than R. euryale, because of its higher wing loading. Although wing loading of R. mehelyi was only 20% larger than that of R. euryale, its flight costs (2.61 +/- 0.75 W; mean +/- 1 SD) exceeded that of R. euryale (1.71 +/- 0.37 W) by 50%. Measured flight costs were higher than predicted for R. mehelyi, but not for R. euryale. We conclude that R. mehelyi face elevated energy costs during short manoeuvring flights due to high wing loading and thus may optimize foraging efficiency by energy-conserving perch-hunting. PMID- 20354706 TI - Timing and risk factors of maternal complications of cesarean section. AB - OBJECTIVE: To investigate the timing and risk factors of maternal complications of cesarean section (CS). METHODS: Review of the files of all women who underwent CS at a tertiary medical center between September 2007 and December 2008 yielded 100 patients with postpartum complications. Their clinical and surgery-related characteristics were compared with 100 women with uncomplicated CS operated in January 2009. Complications were analyzed by prevalence and time of occurrence. RESULTS: The only between-group difference in background factors was a higher rate of obesity (BMI > 30) in the controls. The complication rate was 5.7%. The most common complication was endomyometritis (3.6%), followed by wound infection (1.8%) and wound hematoma (1.2%). In most cases, endomyometritis was diagnosed on postoperative days 2-3 and wound complications on days 2-5; 7 of the 9 readmissions occurred on postoperative days 5-6. On multivariate analysis, significant independent predictors of postoperative complications were surgeon experience (OR = 2.4, 95% CI 1.2-4.8) and intra-partum CS (OR = 2.1, 95% CI 1.1 4.3). CONCLUSION: Cesarean section performed by a resident or during active labor is associated with an increased risk of postpartum complications. Medical teams should be alert to morbidity in women at risk, particularly during the first 4 days after CS. PMID- 20354707 TI - Association between tobacco use in pregnancy and placenta-associated syndromes: a population-based study. AB - INTRODUCTION: Cigarette smoking is an established risk factor for adverse perinatal outcomes. The purpose of this study is to examine the association between maternal smoking in pregnancy and the occurrence of placental-associated syndromes (PAS). METHODS: We analyzed data from a population-based retrospective cohort of singleton deliveries that occurred in the state of Missouri from 1989 through 2005 (N = 1,224,133). The main outcome was PAS, a composite outcome defined as the occurrence of placental abruption, placenta previa, preeclampsia, small for gestational age, preterm or stillbirth. We used logistic regression models to generate adjusted odd ratios and their 95 percent confidence intervals. Non-smoking gravidas served as the referent category. RESULTS: The overall prevalence of prenatal smoking was 19.6%. Cigarette smoking in pregnancy was associated with the composite outcome of placental syndromes (odds ratio, 95% confidence interval = 1.59, 1.57-1.60). This association showed a dose-response relationship, with the risk of PAS increasing with increased quantity of cigarettes smoked. Similar results were observed between smoking in pregnancy and independent risks for abruption, previa, SGA, stillbirth, and preterm delivery. CONCLUSION: Maternal smoking in pregnancy is a risk factor for the development of placenta-associated syndrome. Smoking cessation interventions in pregnancy should continue to be encouraged in all maternity care settings. PMID- 20354708 TI - Human papillomavirus genotypes distribution in cervical samples from women living with human immunodeficiency virus. AB - BACKGROUND: The aim of this study was to determine the prevalence and relationship of human papillomavirus (HPV) genotypes in cervical samples from 140 human immunodeficiency virus (HIV)-seropositive women routinely attending an outpatient public gynecological service in the state of Rio de Janeiro, Brazil. METHODS: MY09/11 consensus primers were used to detect generic HPV DNA. HPV typification was performed by restriction fragment length polymorphism analysis following polymerase chain reaction amplification. RESULTS: The overall HPV prevalence was 60.0%. The identification of 24 different HPV genotypes including uncommon types was performed. A9 oncogenic genotypes were present in 54.02% of HIV-positive women. Abnormal cervical lesions, the time since HIV diagnosis and the number of sexual partners contributed independently to the high oncogenic HPV prevalence. The oncogenic and non-oncogenic group were similarly affected by risk factors in contrast to negative HPV women. The frequency of multiple infections was 20%; furthermore, all of them presented at least one oncogenic type. CONCLUSION: The analyzed sample represents an epidemiological source of uncommon infection. Due to high HPV prevalence, more frequent cytological screening and/or liberal colposcopic evaluations should be performed in HIV-positive patients. PMID- 20354709 TI - Cephalothoracopagus, janiceps, disymmetros, monoomphalian conjoined twins undiagnosed until early second trimester. AB - INTRODUCTION: Cephalothoracopagus is the less common type of conjoined twins (CTs) with an incidence estimated at one in three million births or one in 58 conjoined twins. Maternal gene Vg1, a member of the TGF-beta family of cell signalling molecules which are implicated in dorsoanterior development, and specific actions of Hox and Pax genes that are implicated in very early embryogenesis may be identified as aetiologic factors. MATERIALS AND METHODS: A prenatal diagnosis of cephalothoracopagus CTs diagnosed at 17 weeks in a woman undergoing amniocentesis for advanced maternal age is reported. CONCLUSION: Although first-trimester diagnosis of CTs is feasible and has been reported as early as 8 weeks's gestation, CTs may be misdiagnosed with monoamniotic twins, lymphangioma, teratoma, and/or neoplasm and may be undiagnosed until early second trimester. Three-dimensional and color Doppler ultrasound enabled precise prenatal visualization of the fusion site. Ultrafast MR imaging should be considered an adjunct to ultrasound for antenatal characterization of structural anomalies and for planning surgical separation in selected cases. Echocardiography is mandatory in all cases of CTs as congenital heart defects are seen in 20-30% and polyhydramnios in 50-75%. Neural tube and midline fusion defects, diaphragmatic hernia, and imperforate anus are the frequently associated abnormalities. Prognosis among survivors is usually poor (44% die in the neonatal period) and is dependent upon the type of conjunction, degree of involvement of the shared organs, and presence or absence of associated anomalies, with the worst prognosis in case of twins sharing liver and heart. PMID- 20354705 TI - Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease. AB - The aberrant accumulation of aggregated beta-amyloid peptides (Abeta) as plaques is a hallmark of Alzheimer's disease (AD) neuropathology and reduction of Abeta has become a leading direction of emerging experimental therapies for the disease. The mechanism(s) whereby Abeta is involved in the pathophysiology of the disease remain(s) poorly understood. Initially fibrils, and subsequently oligomers of extracellular Abeta have been viewed as the most important pathogenic form of Abeta in AD. More recently, the intraneuronal accumulation of Abeta has been described in the brain, although technical considerations and its relevance in AD have made this a controversial topic. Here, we review the emerging evidence linking intraneuronal Abeta accumulation to the development of synaptic pathology and plaques in AD, and discuss the implications of intraneuronal beta-amyloid for AD pathology, biology, diagnosis and therapy. PMID- 20354710 TI - The relation between sleep and pain among a non-clinical sample of young adults. AB - Poor sleep is linked to poorer daily functioning and increased risk of psychiatric symptoms. With respect to pain, the relation is bi-directional; poor sleep exacerbates pain, while greater pain adversely affects sleep. Moreover, perception of pain is subject to cognitive-emotional processes. Surprisingly, no data are available from non-clinical samples of young adults. The aim of the present study was therefore to investigate the relation between sleep and pain as a function of quality of life and depressive symptoms in young adults. The direction of influence between sleep and pain was statistically tested with two different structural equation models (SEMs). A total of 862 participants (639 women, 223 men; mean age: 24.67; SD = 5.91) completed a series of validated self report questionnaires assessing sleep, quality of life, depressive symptoms and cognitive-emotional elaboration of pain. Sleep, pain, quality of life, and depressive symptoms were interrelated. The first SEM suggested both a direct and an indirect influence of pain on sleep, whereas the second SEM suggested that sleep had only an indirect influence on pain. Irrespective of the SEM, the relation between sleep and cognitive-emotional elaboration of pain was mediated by quality of life and depressive symptoms. For a non-clinical sample of young adults, findings did support the bi-directional relation between poor sleep and increased cognitive-emotional elaboration of pain, though other cognitive emotional processes such as depressive symptoms and quality of life should be taken into account. PMID- 20354711 TI - Enhanced possibilities to make statements on the ossification status of the medial clavicular epiphysis using an amplified staging scheme in evaluating thin slice CT scans. AB - Thin-slice computed tomography provides the imaging modality of choice in analysing the ossification process of the medial clavicular epiphysis for the purpose of forensic age diagnostics in the living in the course of criminal proceedings. The classification of the ossification stages by Schmeling et al. compass the emergence of an epiphyseal ossification centre (stage 2), the partial fusion of the epiphysis with the metaphysis (stage 3), the complete fusion of these osseous elements including a visible epiphyseal scar (stage 4), and the complete fusion without a visible epiphyseal scar (stage 5). In the present study, each of the ossification stages 2 and 3 was divided into an early, intermediate and late phase. The authors evaluated the thin-slice CT scans of 185 patients aged between 13 and 26 years. In all these cases, a stage 2 or 3 had been determined in a previous study. The late stage 3, which is characterized by a fusion between metaphysis and epiphysis completing more than two thirds of the former epiphyseal gap, first appeared at age 19 in both sexes. If a late stage 3 is found, it is therefore possible to substantiate that an individual has already reached the legally important age threshold of 18 years. PMID- 20354713 TI - X-linked insertion/deletion polymorphisms: forensic applications of a 33-markers panel. AB - Insertion/deletion (INDEL) polymorphisms are diallelic markers with potential characteristics for use in forensics and biological anthropology, including: the simplicity of laboratory analysis, the possibility of genotyping many markers in a single PCR multiplex reaction, as well as analyzing markers with special inheritance types, such as those linked to the X chromosome (X-INDEL). In this work we developed a laboratory analysis methodology using a 33-INDEL marker panel for the X chromosome in a single PCR multiplex reaction, followed by a capillary electrophoresis run. We employed the panel to genotype a sample of 351 individuals of a mixed population from the Brazilian Amazon. The results demonstrate that the measurement of biostatistical parameters for forensic use in this population is compatible with prior estimates from other populations using current X-STR panels. PMID- 20354712 TI - Identification of poisonous plants by DNA barcoding approach. AB - The plant exposures are one of the most frequent poisonings reported to poison control centres. The diagnosis of intoxicated patients is usually based on the morphological analysis of ingested plant portions; this procedure requires experience in systematic botany, because the plant identification is based on few evident traits. The objective of this research is to test DNA barcoding approach as a new universal tool to identify toxic plants univocally and rapidly. Five DNA barcode regions were evaluated: three cpDNA sequences (trnH-psbA, rpoB and matK) and two nuclear regions (At103 and sqd1). The performance of these markers was evaluated in three plant groups: (1) a large collection of angiosperms containing different toxic substances, (2) congeneric species showing different degrees of toxicity and (3) congeneric edible and poisonous plants. Based on assessments of PCR, sequence quality and resolution power in species discrimination, we recommend the combination of plastidial and nuclear markers to identify toxic plants. Concerning plastidial markers, matK and trnH-psbA showed consistent genetic variability. However, in agreement with CBOL Plant Working Group, we selected matK as the best marker, because trnH-psbA showed some problems in sequences sizes and alignments. As a final and relevant observation, we also propose the combination of matK with a nuclear marker such as At103 to distinguish toxic hybrids form parental species. In conclusion, our data support the claim that DNA barcoding is a powerful tool for poisonous plant identifications. PMID- 20354714 TI - Wartenberg's migrant sensory neuritis: a prospective follow-up study. AB - Migrant sensory neuropathy (Wartenberg's migrant sensory neuritis) is characterized by sudden numbness in the distribution of one or multiple cutaneous nerves. To study disease course and outcome, we prospectively followed 12 patients who presented to our tertiary referral neuromuscular outpatient clinic between January 2003 and January 2004. Medical history, neurological, laboratory and electrophysiological examinations were obtained from all patients. All patients were reviewed a second time in 2007, and five had a follow-up electrophysiological examination. At the first visit, 50% described an episode of stretching preceding the sensory complaints. All but three described pain in the affected area before or concomitant with sensory loss. At clinical examination a median of six skin areas were affected, and in 75% this could be confirmed by nerve conduction studies in at least one nerve. Forty-two percent had involvement of the trigeminal nerve. After a mean disease duration of 7.5 years, three patients reported a complete disappearance of sensory complaints and five that the pain had disappeared, but numbness remained. Three patients still had both painful and numb sensory deficits. One patient developed a distal symmetric sensory polyneuropathy. In conclusion, Wartenberg's sensory neuritis is a distinct, exclusively sensory, neuropathy, marked by pain preceding numbness in affected nerves. An episode of stretching preceding pain is not necessary for the diagnosis. Wartenberg's sensory neuritis often retains its spotty, exclusively sensory characteristics after long term follow-up. PMID- 20354715 TI - Relation between intracranial artery calcifications and aortic atherosclerosis in ischemic stroke patients. AB - We previously demonstrated a strong relation between carotid atherosclerosis (defined as carotid artery stenosis > or =50%) and intracranial artery calcification (IAC) in ischemic stroke patients. The purpose of this study was to evaluate the relation between aortic atherosclerosis and IAC. Four hundred fifty four patients with ischemic stroke were included. Complex aortic plaques (CAP) were assessed by transesophageal echocardiography (TEE) and defined as plaques > or =4 mm thick or with mobile components in the proximal aorta. IAC were assessed in the seven major cerebral arteries and a semiquantitative score system was applied, ranging from 0 (no calcification) to 7. Forty-two patients (9.3%) had CAP. Patients with CAP were older compared with patients without CAP (73.6 vs. 63.6 years, p < 0.001), had more vascular risk factors, more significant carotid artery atherosclerosis (p < 0.001), more chronic kidney disease (p < 0.001), and a higher IAC score (3.0 vs. 1.8; p < 0.001). Stepwise logistic regression selected the following independent factors for CAP: previous stroke or TIA (OR 3.3; 95%CI 1.5-7.0; p = 0.002), carotid artery stenosis > or =50% (OR 3.7; 95%CI 1.7-8.0; p = 0.001), chronic kidney disease (OR 3.8; 95%CI 1.9-7.8; p < 0.001), and IAC score (OR 1.5; 95%CI 1.2-1.9; p = 0.002). IAC was present in 100% of patients with CAP. Moreover, IAC had a high sensitivity (100%) and negative predictive value (100%) for the presence of CAP. In ischemic stroke patients, the absence of IAC strongly points to the lack of CAP. However, these results warrant confirmation in prospective studies before concluding the non-utility of the use of TEE to exclude CAP as a potential source of cerebral embolism in patients without IAC. PMID- 20354716 TI - Diffusion tensor imaging reveals disease-specific deep cerebellar nuclear changes in cerebellar degeneration. PMID- 20354717 TI - Physiological effects of wearing graduated compression stockings during running. AB - This study examined the effect of wearing different grades of graduated compression stockings (GCS) on physiological and perceptual measures during and following treadmill running in competitive runners. Nine males and one female performed three 40-min treadmill runs (80 +/- 5% maximal oxygen uptake) wearing either control (0 mmHg; CON), low (12-15 mmHg; LO-GCS), or high (23-32 mmHg; HI GCS) grade GCS in a double-blind counterbalanced order. Oxygen uptake, heart rate and blood lactate were measured. Perceptual scales were used pre- and post-run to assess comfort, tightness and any pain associated with wearing GCS. Changes in muscle function, soreness and damage were determined pre-run, immediately after running and 24 and 48 h post-run by measuring creatine kinase and myoglobin, counter-movement jump height, perceived soreness diagrams, and pressure sensitivity. There were no significant differences between trials for oxygen uptake, heart rate or blood lactate during exercise. HI-GCS was perceived as tighter (P < 0.05) and more pain-inducing (P < 0.05) than the other interventions; CON and LO-GCS were rated more comfortable than HI-GCS (P < 0.05). Creatine kinase (P < 0.05), myoglobin (P < 0.05) and jump height (P < 0.05) were higher and pressure sensitivity was more pronounced (P < 0.05) immediately after running but not after 24 and 48 h. Only four participants reported muscle soreness during recovery from running and there were no differences in muscle function between trials. In conclusion, healthy runners wearing GCS did not experience any physiological benefits during or following treadmill running. However, athletes felt more comfortable wearing low-grade GCS whilst running. PMID- 20354718 TI - Influence of cerebral and muscle oxygenation on repeated-sprint ability. AB - The study examined the influence of cerebral (prefrontal cortex) and muscle (vastus lateralis) oxygenation on the ability to perform repeated, cycling sprints. Thirteen team-sport athletes performed ten, 10-s sprints (with 30 s of rest) under normoxic (F(I)O(2) 0.21) and acute hypoxic (F(I)O(2) 0.13) conditions in a randomised, single-blind fashion and crossover design. Mechanical work was calculated and arterial O(2) saturation (S(p)O(2)) was estimated via pulse oximetry for every sprint. Cerebral and muscle oxy-(O(2)Hb), deoxy-(HHb), and total haemoglobin (THb) were monitored continuously by near-infrared spectroscopy. Compared with normoxia, hypoxia induced larger decrements in S(p)O(2) and work (11.6 and 7.6%, respectively; P < 0.05). In the muscle, we observed a fairly constant level of deoxygenation across sprints, with no effect of the condition. In normoxia, regional cerebral oxygenation increased during the first two sprints and slightly fluctuated thereafter. In contrast, this initial cerebral hyper-oxygenation was attenuated in hypoxia. Changes in [O(2)Hb] and [HHb] occurred earlier and were larger in hypoxia compared with normoxia (P < 0.05), while regional blood volume (Delta[THb]) remained unaffected by the condition. Changes in cerebral [HHb] and mechanical work were strongly correlated in normoxia and hypoxia (R(2) = 0.81 and R(2) = 0.85, respectively; P < 0.05), although the slope of this relationship differed (normoxia, -351.3 +/- 183.3 vs. hypoxia, -442.4 +/- 227.2; P < 0.05). The results of this NIRS study show that O(2) availability influences prefrontal cortex, but not muscle, oxygenation during repeated, short sprints. By using a hypoxia paradigm, the study suggests that cerebral oxygenation contributes to the impairment of repeated-sprint ability. PMID- 20354721 TI - Schema generation in recurrent neural nets for intercepting a moving target. AB - The grasping of a moving object requires the development of a motor strategy to anticipate the trajectory of the target and to compute an optimal course of interception. During the performance of perception-action cycles, a preprogrammed prototypical movement trajectory, a motor schema, may highly reduce the control load. Subjects were asked to hit a target that was moving along a circular path by means of a cursor. Randomized initial target positions and velocities were detected in the periphery of the eyes, resulting in a saccade toward the target. Even when the target disappeared, the eyes followed the target's anticipated course. The Gestalt of the trajectories was dependent on target velocity. The prediction capability of the motor schema was investigated by varying the visibility range of cursor and target. Motor schemata were determined to be of limited precision, and therefore visual feedback was continuously required to intercept the moving target. To intercept a target, the motor schema caused the hand to aim ahead and to adapt to the target trajectory. The control of cursor velocity determined the point of interception. From a modeling point of view, a neural network was developed that allowed the implementation of a motor schema interacting with feedback control in an iterative manner. The neural net of the Wilson type consists of an excitation-diffusion layer allowing the generation of a moving bubble. This activation bubble runs down an eye-centered motor schema and causes a planar arm model to move toward the target. A bubble provides local integration and straightening of the trajectory during repetitive moves. The schema adapts to task demands by learning and serves as forward controller. On the basis of these model considerations the principal problem of embedding motor schemata in generalized control strategies is discussed. PMID- 20354720 TI - Bioenergetics and biomechanics of cycling: the role of 'internal work'. AB - The 'dissection' of energy expenditure of cycling into the metabolic equivalent of the different forms of mechanical work done, inaugurated 30 years ago by di Prampero and collaborators, has been much debated in the last few decades. The mechanical internal work, particularly, which is currently associated to the movement of the lower limbs, has been approached, estimated and discussed in several different ways and there is no agreed consensus on its role in cycling. This paper, through re-processing previously published data of oxygen consumption during pedalling at different frequency, external load and limb mass, proposes a model equation and a multiple non-linear regression as the method to assess the internal work of cycling. With that tool a very consistent metabolic equivalent of the internal work is obtained. However, a software simulation of pedalling limbs showed, as suggested in the literature, that the link with the chain ring allows the system to passively revolve forever, after an initial push. This result challenges the very existence of the 'kinematic internal work' of cycling. We conclude and suggest that the 'viscous internal work', an often neglected and almost unmeasurable portion of the internal work that could be proportional to the 'kinematic' form, is responsible for the extra metabolic expenditure as measured when the pedalling frequency of cycling increases. PMID- 20354719 TI - Influence of age, sex, and aerobic capacity on forearm and skin blood flow and vascular conductance. AB - This study investigated the influence of age, sex, and aerobic capacity on resting and peak forearm and cutaneous blood flow (FBF, CBF). We recruited 93 female and 129 male subjects (age range 16-76 years). FBF and CBF were assessed by plethysmography and laser-Doppler flowmetry, respectively. Peak FBF was obtained following 5 min forearm vascular occlusion and peak CBF in response to local skin heating of 42 degrees C. Blood pressure was measured manually and by Finapres. Maximal oxygen uptake (VO2max) was obtained from a treadmill exercise stress test. Age was associated with declines in resting FBF (y = -1.176 ln(x) + 6.6899, r(2) = 0.45) and peak FBF (y = -17.21 ln(x) + 93.843, r(2) = 0.53) (both p < 0.05). Peak CBF decreased with increasing age (y = -223.6 ln(x) + 1,102.9, r(2) = 0.34) (p < 0.05), but resting CBF was unchanged (p > 0.05). Males had higher resting and peak FBF than females (p < 0.05) and these variables were related to ageing better in males (y = -1.245 ln(x) + 7.188, r(2) = 0.71 and y = 18.53 ln(x) + 102.82, r(2) = 0.69) than in females (y = -1.149 ln(x) + 6.4307, r(2) = 0.38 and y = -16.59 ln(x) + 88.872, r(2) = 0.55). There were no sex differences in resting CBF (p > 0.05). Peak CBF was much better related to ageing in males than females (y = -276.1 ln(x) + 1,365.4, r(2) = 0.53 vs. y = -183.1 ln(x) + 907.86, r(2) = 0.28). VO2max decreased with advancing age and this decline was associated with the decline in peak FBF (y = -0.5933x + 10.91, r(2) = 0.36, p < 0.05) but not with peak CBF (p > 0.05). These results suggest that healthy ageing is associated with a curvilinear decline in resting and peak forearm and peak cutaneous vasodilator capacity, with males more severely affected than females. The data indicate that peak FBF is influenced by VO2max but peak CBF is not. PMID- 20354722 TI - Face, content and construct validity of a new realistic trainer for conventional techniques in digestive surgery. AB - PURPOSE: Surgical simulation modules for "open" surgery are limited in contrast to well-studied and validated laparoscopic trainers. In this study, face, content and construct validity of a devised simulation module (Berlin Operation Trainer, BOPT) for handsewn anastomoses in digestive surgery were analysed. MATERIALS AND METHODS: Participants of a skills course for digestive surgery (novices: 1-3 years of training; experts: more than 5 years of training) were timed on performing four defined handsewn digestive anastomoses on formalin fixed porcine intestine in the BOPT. Questionnaires were answered regarding impression with the simulation module concerning appearance and realism using a five-point Likert and a three-point forced choice scale. Face and content validities were evaluated based on the responses of participants and construct validity by comparing novices to experts. Data collected were analysed with Fisher's exact test and two sample t test. RESULTS: Twenty-two novices (median: second postgraduate year) and 26 experts (median: seventh postgraduate year) were enrolled in the study. The BOPT showed strong face and content validities with average scores for satisfaction parameters above 4.2 +/- 0.41 and 4.1 +/- 0.22, respectively. Construct validity was adequate for anastomosis simulation in the BOPT based on different percentages of anastomosis complete during set time between novices and experts as shown for simple (68.2% vs. 92.3%, p = 0.038) and for difficult anastomosis (18.2% vs. 50.0%, p = 0.021). CONCLUSIONS: The BOPT is a suitable instrument for advanced surgical training for novices and experienced colleagues creating a realistic and demanding situation. Further studies have to evaluate if a more realistic preoperative training will support an effective transfer of learned techniques to the operating room. PMID- 20354723 TI - Laparoscopic Toupet fundoplication. AB - This article and video presents our Toupet procedure. It is a modern adaptation of Toupet's original technique. Toupet described his technique of fundoplication in 1963 (Toupet, Mem Aca Chir 89:394, 1963). He had little experience but saw the importance of a partial wrap to avoid postoperative dysphagia. He recommended closure of the hiatus only in case of large hernias and never divided the short gastric vessels. If we talk about a Toupet procedure today, we mean a posterior partial fundoplication. In contrary to his original technique, we have learned that hiatal closure is important to avoid recurrent hernia and that the wrap in most cases can be tailored more nicely if the short gastric vessels are divided. This modern adaptation of the Toupet's operation is a very successful tool to treat gastro-oesophageal reflux disease. PMID- 20354724 TI - Cyanoacrylate-assisted arterial anastomosis in rat small bowel transplantation. AB - PURPOSE: Microarterial anastomosis in rat small bowel transplantation (SBTx) remains technically difficult and time-consuming especially for beginners of microsurgery. In the exploration of the facilitated microarterial anastomosis strategies, we assessed the performance of n-butyl-cyanoacrylate-assisted suture technique (CAST) in comparison with simple continuous suture technique (SCST). METHODS: Allogeneic small bowel transplantation was performed in a rat combination of F344 to Lewis. CAST and SCST were used for anastomosis of graft superior mesenteric artery to recipient infrarenal aorta. Success rate of anastomosis, anastomosis time, anastomotic bleeding, and stenosis as well as tissue reactivity of suture materials and their influence on allograft rejection were compared between the two techniques. RESULTS: CAST significantly reduced anastomosis time and anastomotic bleeding, although its success rate was similar to SCST. Moreover, CAST created regularly shaped anastomotic orifice and smooth luminal surface along the anastomotic line, and provided higher blood flow of graft superior mesenteric artery. The use of n-butyl-cyanoacrylate caused moderate to mild tissue reaction that was comparable to nylon suture; and it did not significantly influence allograft rejection. CONCLUSIONS: CAST is a simple, effective, and safe surgical technique for microarterial anastomosis in rat SBTx. It deserves the interest in exploration of facilitated microarterial anastomosis strategies in animal experiments as well as in clinical settings. PMID- 20354726 TI - Conscious thought beats deliberation without attention in diagnostic decision making: at least when you are an expert. AB - Contrary to what common sense makes us believe, deliberation without attention has recently been suggested to produce better decisions in complex situations than deliberation with attention. Based on differences between cognitive processes of experts and novices, we hypothesized that experts make in fact better decisions after consciously thinking about complex problems whereas novices may benefit from deliberation-without-attention. These hypotheses were confirmed in a study among doctors and medical students. They diagnosed complex and routine problems under three conditions, an immediate-decision condition and two delayed conditions: conscious thought and deliberation-without-attention. Doctors did better with conscious deliberation when problems were complex, whereas reasoning mode did not matter in simple problems. In contrast, deliberation-without-attention improved novices' decisions, but only in simple problems. Experts benefit from consciously thinking about complex problems; for novices thinking does not help in those cases. PMID- 20354727 TI - The role of tumor invasion into the mandible of oral squamous cell carcinoma. AB - PURPOSE: The aim of this study was to determine the prognostic impact of the extent of bone invasion in patients undergoing mandibulectomy for oral squamous cell carcinoma (OSCC), and to evaluate the relation between clinicopathologic parameters and outcome. METHODS: Nine hundred and eighty-two patients presented with OSCC and 334 were treated surgically by some form of mandibular excision. Treatment included marginal, rim, or segmental mandibulectomy depending on the clinical and radiological observation of the mandible and suspected bone invasion. Kaplan-Meier plots and univariate log-rank test and multivariate Cox proportional hazards regression models were used to determine the association between possible predictor variables and survival time. RESULTS: After controlling for age, tumor and nodal stage, UICC stage, type of reconstruction, which were independent predictors of survival, type of mandibulectomy was significantly associated with survival in the univariate analysis (P = 0.038), whereas bone invasion was not in both univariate and multivariate analysis. The rate of bone invasion detected after marginal mandibulectomy was 15.5%, in rim resections 50%, and segmental mandibulectomy at 84.7%. Recurrence of OSCC was found to be associated with overall survival (P = 0.039). CONCLUSIONS: If bone invasion is identified histologically in a resected specimen, the prognosis is not worsened and additional surgery need not be undertaken in adequately resected margins. Although the mandible should be preserved if feasible, the choice of treatment should always provide safe resection margin. The high rates of unsuspected bone invasion found in this study should be kept in mind in patients with OSCC close to the mandible. PMID- 20354728 TI - Heritability of chronic venous disease. AB - Varicose veins without skin changes have a prevalence of approximately 20% in Northern and Western Europe whereas advanced chronic venous insufficiency affects about 3% of the population. Genetic risk factors are thought to play an important role in the aetiology of both these chronic venous diseases (CVD). We evaluated the relative genetic and environmental impact upon CVD risk by estimating the heritability of the disease in 4,033 nuclear families, comprising 16,434 individuals from all over Germany. Upon clinical examination, patients were classified according to the CEAP guidelines as either C2 (simple varicose veins), C3 (oedema), C4 (skin changes without ulceration), C5 (healed ulceration), or C6 (active ulcers). The narrow-sense heritability (h2) of CVD equals 17.3% (standard error 2.5%, likelihood ratio test P = 1.4 x 10(-13)). The proportion of disease risk attributable to age (at ascertainment) and sex, the two main risk factors for CVD, was estimated as 10.7% (Kullback-Leibler deviance R2). The heritability of CVD is high, thereby suggesting a notable genetic component in the aetiology of the disease. Systematic population-based searches for CVD susceptibility genes are therefore warranted. PMID- 20354729 TI - Plant genotype mediates the effects of nutrients on aphids. AB - Soil nutrients, and factors which influence their concentrations and bioavailability, form a basic component of bottom-up control of ecosystem processes, including plant-herbivore interactions. Increased nutrient levels are linked, through plant defence theory, with increased levels of herbivore susceptibility. The focal point of many ecological experiments examining this link is at the species level, where the response of single species is the average of many different genotypes. Here, we focus on the genetic basis of indirect ecological interactions. We investigated the effects of nutrient concentration on the population growth of an aphid herbivore across multiple genotypes of barley in relation to plant growth rate. In general, both aphid population size and plant growth rate increased with nutrient concentration. However, they were both dependent on the interaction between nutrient concentration and barley genotype. Our data raise the testable possibility of differential defense responses between genotypes of barley, for example divergent, fixed and inducible defences against aphids. We provide evidence that the indirect effects of soil nutrients on aphid population size are mediated by the genetics of the host plant. PMID- 20354730 TI - Cues of intraguild predators affect the distribution of intraguild prey. AB - Theory on intraguild (IG) predation predicts that coexistence of IG-predators and IG-prey is only possible for a limited set of parameter values, suggesting that IG-predation would not be common in nature. This is in conflict with the observation that IG-predation occurs in many natural systems. One possible explanation for this difference might be antipredator behaviour of the IG-prey, resulting in decreased strength of IG-predation. We studied the distribution of an IG-prey, the predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae), in response to cues of its IG-predator, the predatory mite Iphiseius degenerans. Shortly after release, the majority of IG-prey was found on the patch without cues of IG-predators, suggesting that they can rapidly assess predation risk. IG prey also avoided patches where conspecific juveniles had been killed by IG predators. Because it is well known that antipredator behaviour in prey is affected by the diet of the predator, we also tested whether IG-prey change their distribution in response to the food of the IG-predators (pollen or conspecific juveniles), but found no evidence for this. The IG-prey laid fewer eggs on patches with cues of IG-predators than on patches without cues. Hence, IG-prey changed their distribution and oviposition in response to cues of IG-predators. This might weaken the strength of IG-predation, possibly providing more opportunities for IG-prey and IG-predators to co-exist. PMID- 20354731 TI - Modeling decay rates of dead wood in a neotropical forest. AB - Variation of dead wood decay rates among tropical trees remains one source of uncertainty in global models of the carbon cycle. Taking advantage of a broad forest plot network surveyed for tree mortality over a 23-year period, we measured the remaining fraction of boles from 367 dead trees from 26 neotropical species widely varying in wood density (0.23-1.24 g cm(-3)) and tree circumference at death time (31.5-272.0 cm). We modeled decay rates within a Bayesian framework assuming a first order differential equation to model the decomposition process and tested for the effects of forest management (selective logging vs. unexploited), of mode of death (standing vs. downed) and of topographical levels (bottomlands vs. hillsides vs. hilltops) on wood decay rates. The general decay model predicts the observed remaining fraction of dead wood (R2 = 60%) with only two biological predictors: tree circumference at death time and wood specific density. Neither selective logging nor local topography had a differential effect on wood decay rates. Including the mode of death into the model revealed that standing dead trees decomposed faster than downed dead trees, but the gain of model accuracy remains rather marginal. Overall, these results suggest that the release of carbon from tropical dead trees to the atmosphere can be simply estimated using tree circumference at death time and wood density. PMID- 20354732 TI - Effects of ingestion by neotropical bats on germination parameters of native free standing and strangler figs (Ficus sp., Moraceae). AB - Fruit-eating animals can influence the germination success of seeds through transportation and handling. We experimentally tested the contribution of ingestion by the common fruit-eating bat, Artibeus jamaicensis (Phyllostomidae, Chiroptera), to the percentage and rate of seed germination of figs (Ficus, Moraceae), which are considered keystone species for many frugivores. We collected fruits from three species of native free-standing figs (subgenus Pharmacosycea: F. insipida, F. maxima and F. yoponensis) and three species of native strangler figs (subgenus Urostigma: F. nymphiifolia, F. obtusifolia and F. popenoei) on Barro Colorado Island, Panama. The germination success of seeds removed from fruit pulp either manually or by ingestion was very high (>92%), while seeds that were not removed from fruit pulp were destroyed by fast-growing fungi within a few days. The dynamics of seed germination were not influenced by ingestion, but differed between the two subgenera of figs. In free-standing figs, germination started significantly earlier (5.3 +/- 0.7 days) than in strangler figs (8.6 +/- 1.4 days). Furthermore, strangler seeds were covered with a sticky coating and their seedlings developed cotyledons faster than fine roots, in contrast to free-standing figs that showed the opposite pattern. Our results demonstrate that the germination of fig seeds is positively influenced by passage through the gut of A. jamaicensis. Furthermore, free-standing and strangler figs revealed differences in germination parameters that might be adaptive with respect to the suitability of microsites such as tree fall gaps or host trees for establishment. PMID- 20354733 TI - Phenological records as a complement to aerobiological data. AB - Phenological studies in combination with aerobiological studies enable one to observe the relationship between the release of pollen and its presence in the atmosphere. To obtain a suitable comparison between the daily variation of airborne pollen concentrations and flowering, it is necessary for the level of accuracy of both sets of data to be as similar as possible. To analyse the correlation between locally observed flowering data and pollen counts in pollen traps in order to set pollen information forecasts, pollen was sampled using a Burkard volumetric pollen trap working continuously from May 1993. For the phenological study we selected the main pollen sources of the six pollen types most abundant in our area: Cupressaceae, Platanus, Quercus, Plantago, Olea, and Poaceae with a total of 35 species. We selected seven sites to register flowering or pollination, two with semi-natural vegetation, the rest being urban sites. The sites were visited weekly from March to June in 2007, and from January to June in 2008 and 2009. Pollen shedding was checked at each visit, and recorded as the percentage of flowers or microsporangia in that state. There was an association between flowering phenology and airborne pollen records for some of the pollen types (Platanus, Quercus, Olea and Plantago). Nevertheless, for the other types (Cupressaceae and Poaceae) the flowering and airborne pollen peaks did not coincide, with up to 1 week difference in phase. Some arguments are put forward in explanation of this phenomenon. Phenological studies have shown that airborne pollen results from both local and distant sources, although the pollen peaks usually appear when local sources are shedding the greatest amounts of pollen. Resuspension phenomena are probably more important than long-distance transport in explaining the presence of airborne pollen outside the flowering period. This information could be used to improve pollen forecasts. PMID- 20354734 TI - Evaluation of analgesic effect and safety of fentanyl transdermal patch for cancer pain as the first line. AB - BACKGROUND: Initial treatment with morphine followed by fentanyl transdermal patch is the standard in Japan, since even the smallest patch (2.5 mg) could deliver too high an initial dose for Japanese patients. We evaluated the analgesic effect and safety of using the fentanyl transdermal patch as a first line strong opioid for cancer pain that is resistant to nonsteroidal anti inflammatory drugs (NSAIDs). PATIENTS AND METHODS: For 20 hospitalized patients with cancer pain that could not be controlled by NSAIDs, the fentanyl transdermal patch (1.25 mg; half of a 2.5-mg patch) was administered as a first-line strong opioid. We used rescue medications depending on the degree of pain, and the dose of fentanyl transdermal patch was adjusted every 3 days. To evaluate analgesic efficacy of the patch, the degree of pain was assessed twice a day, in the morning and at night, using a face rating scale. The formulation and dose of morphine used during observation period were recorded. The safety of treatment was evaluated by measuring vital signs once a day, and the severity of side effects were evaluated. Any abnormal findings in blood and urine test were recorded. RESULTS: The median pain score before administration of fentanyl transdermal patch was 3 + or - 0.58 and was decreased to 2 + or - 0.71 on day 9 of administration. The mean dose of fentanyl transdermal patch on day 9 of administration was 2.31 + or - 1.34 mg, and the mean dose of morphine as rescue therapy was 4.62 + or - 7.76 mg. No clinically significant changes in vital signs were observed. No severe adverse events were present when the dose of the fentanyl transdermal patch was 1.25 mg, but two patients experienced dizziness when the dose was increased from 2.5 to 5 mg. No abnormal laboratory data appeared during the administration. CONCLUSION: The use of 1.25-mg fentanyl transdermal patch (50% of a 2.5-mg patch) seems to be safe and efficient as a first-line strong opioid. The use of 3.75-mg fentanyl transdermal patch may be necessary since adverse events including nausea and sleepiness are likely to occur by increasing from 2.5 to 5 mg. PMID- 20354735 TI - Role of cystoperitoneal shunt in the setup of cystic vestibular schwannomas drainage. PMID- 20354736 TI - Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy: a preliminary study of ten patients. AB - BACKGROUND: After a brain biopsy, the genetic analysis can fail because of insufficient material, extensive tumor necrosis, and formalin fixation under conditions that adversely affected the quality of the DNA or because the assay result was indeterminant. The freezing of fresh tumor tissue at surgery could greatly improve the success of DNA extraction and methyl guanine methyl transferase (MGMT) promoter methylation testing. The concentration of the DNA samples can also be improved from a withdrawal in an area with a high probability of neoplastic cells. METHODS: The present study reports the results of ten frameless image-guided intracranial needle biopsies from April 2008 until February 2009, among a total of 28 frameless neuronavigation brain biopsy performed from May 2007 to February 2009. The protocol sampling provided withdrawal specimens correlated with neuroimaging characteristics of the lesions. The molecular determination of MGMT promoter was assessed with the nested methylation-specific polymerase chain reaction on fresh or cryopreserved needle bioptic tissue. RESULTS: The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in six patients, including a brain infection. The image-guided trajectory of the biopsy and the intraoperative frozen section increased the diagnostic yield. CONCLUSIONS: To the best of the authors' knowledge, this is the first report with the MGMT promoter status analysis on needle bioptic fresh tissue. In the future, the availability of the molecular genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. PMID- 20354737 TI - Non-invasive repositioning of the ventricular catheter after suboptimal ventriculoperitoneal shunt placement. PMID- 20354738 TI - Purification, characterization, structural analysis and protein chemistry of a buffalo heart galectin-1. AB - A soluble beta-galactoside-binding lectin was purified by gel filtration chromatography from Bubalus bubalis heart. Its metal-independent nature, molecular weight of 14.5 kDa, preferential affinity for beta-D-lactose, and 87 92% identity with carbohydrate recognition domain of previously reported galectin 1 confirmed its inclusion in galectin-1 subfamily. Stokes radii determination using gel filtration under reducing and non-reducing conditions revealed its homo dimeric nature, further confirming its Gal-1 nomenclature. The purified lectin was found to be the most stable mammalian heart galectin purified till date, suggesting its preferential use in various recognition studies. Treatment of the purified lectin with oxidizing agent, thiol blocking reagents, denaturants, and detergents resulted in significant changes in UV-VIS, fluorescence, CD and FTIR spectra, which strongly emphasized the important aspect of regular secondary structure of galectins for the maintenance of their active conformation. Reduction of the activity of the purified lectin after oxidation by H2O2, with remarkable fluorescence quenching, may suggest potential role for galectin-1 in free radical-induced, oxidative stress-mediated cardiovascular disorders. The predictions of bioinformatics studies were found to be in accordance with the results obtained in wet lab. PMID- 20354739 TI - Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation. AB - The oligomeric state of human porphobilinogen synthase (PBGS) [EC.4.2.1.24] is homooctamer, which consists of conformationally heterogenous subunits in the tertiary structure under air-saturated conditions. When PBGS is activated by reducing agent with zinc ion, a reservoir zinc ion coordinated by Cys(223) is transferred in the active center to be coordinated by Cys(122), Cys(124), and Cys(132) (Sawada et al. in J Biol Inorg Chem 10:199-207, 2005). The latter zinc ion serves as an electrophilic catalysis. In this study, we investigated a conformational change associated with the PBGS activation by reducing agent and zinc ion using analytical ultracentrifugation, negative staining electron microscopy, native PAGE, and enzyme activity staining. The results are in good agreement with our notion that the main component of PBGS is octamer with a few percent of hexamer and that the octamer changes spatial subunit arrangement upon reduction and further addition of zinc ion, accompanying decrease in f/f (0). It is concluded that redox-regulated PBGS activation via cleavage of disulfide bonds among Cys(122), Cys(124), and Cys(132) and coordination with zinc ion is closely linked to change in the oligomeric state. PMID- 20354740 TI - Comparative metabolomics charts the impact of genotype-dependent methionine accumulation in Arabidopsis thaliana. AB - Methionine (Met) is an essential amino acid for all organisms. In plants, Met also functions as a precursor of plant hormones, polyamines, and defense metabolites. The regulatory mechanism of Met biosynthesis is highly complex and, despite its great importance, remains unclear. To investigate how accumulation of Met influences metabolism as a whole in Arabidopsis, three methionine over accumulation (mto) mutants were examined using a gas chromatography-mass spectrometry-based metabolomics approach. Multivariate statistical analyses of the three mto mutants (mto1, mto2, and mto3) revealed distinct metabolomic phenotypes. Orthogonal projection to latent structures-discriminant analysis highlighted discriminative metabolites contributing to the separation of each mutant and the corresponding control samples. Though Met accumulation in mto1 had no dramatic effect on other metabolic pathways except for the aspartate family, metabolite profiles of mto2 and mto3 indicated that several extensive pathways were affected in addition to over-accumulation of Met. The pronounced changes in metabolic pathways in both mto2 and mto3 were associated with polyamines. The findings suggest that our metabolomics approach not only can reveal the impact of Met over-accumulation on metabolism, but also may provide clues to identify crucial pathways for regulation of metabolism in plants. PMID- 20354741 TI - Structural elucidation of Leuprolide and its analogues in solution: insight into their bioactive conformation. AB - Leuprolide [DLeu6, NHEt10]GnRH, a potent gonadotropin-releasing hormone (GnRH) agonist, is used in a wide variety of hormone-related diseases like cancer and endometriosis. In this report, the conformational behaviour of Leuprolide and its linear synthetic analogues, namely [Tyr5(OMe), DLeu6, Aze9, NHEt10]GnRH (1) and [Tyr5(OMe), DLeu6, NHEt10]GnRH (2) have been studied in DMSO and H2O solutions by means of 2D nuclear magnetic resonance (NMR) experiments and detailed molecular dynamics (MD) simulations. The aim was to identify the conformational requirements of GnRH analogues for agonistic activity. This approach is of value as no crystallographic data are available for the GnRH receptor (G protein coupled receptor, GPCR). The NOE data indicate the existence of a beta-turn type I in the 2-5 segments of Leuprolide and its linear analogues in the case of using DMSO-d6 as solvent, whereas a beta-turn type II in the 3-6 segments is indicated using D2O as solvent. The final structures fulfil the conformational requirements that are known, in the literature, to play a significant role in receptor recognition and activation. Finally, the linear analogues (1) and (2) are biologically active when tested against the human breast cancer cell line, MCF-7. PMID- 20354742 TI - Treatment of experimental osteonecrosis of the hip in adult rabbits with a single local injection of recombinant human FGF-2 microspheres. AB - Basic fibroblast growth factor (FGF-2) exerts anabolic actions on bone formation. Here we investigated the potential effects of recombinant human FGF-2 (rhFGF-2) on the repair process of osteonecrosis of the femoral head (ONFH) and the development of secondary osteoarthritis (OA) in adult rabbits. ONFH was induced by intramuscular injection with methylprednisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation, in adult Japanese white rabbits. Animals were randomized into two groups: treatment and control. The treatment group was given a single local injection into the femoral head of 100 MUg rhFGF-2 in 100 MUl gelatin hydrogel microspheres 8 weeks after the ONFH procedure, and the control group was given phosphate-buffered saline in 100 MUl gelatin hydrogel microspheres. Morphological, histopathological, and radiologic analyses, including micro-computed tomography scans and magnetic resonance imaging, showed collapse of the femoral head and progression of articular cartilage degeneration in the control group at 16 weeks after the single local injection of rhFGF-2. In contrast, rhFGF-2 treatment resulted in new bone formation in the femoral head and prevented the femoral head from collapsing. In addition, the changes in OA, assessed by the modified Mankin score, was significantly lower in the treatment group. Our results indicate that a single local injection of rhFGF-2 microspheres promoted the repair of the osteonecrotic femoral head and inhibited femoral head collapse and OA progression. rhFGF-2 may be a promising strategy for the treatment of ONFH. PMID- 20354744 TI - Incarcerated internal hernia of the small intestine through a re-approximated peritoneum after a trans-abdominal pre-peritoneal procedure--apropos of two cases: review of the literature. AB - A description of two cases of internal herniation caused by a defect in the closure of the peritoneal flap during a trans-abdominal pre-peritoneal procedure is presented here. They were both successfully treated laparoscopically. This rare condition should be considered when patients who have had recent trans abdominal surgery for inguinal hernia repair present with colicky lower abdominal pain--its aetiology may well be due to technical error. It is already established that laparoscopy is useful as a diagnostic and therapeutic tool in emergency cases, but it is also true that it is useful in case of early post-operative period complications following any laparoscopic procedure, such as the laparoscopic inguinal hernia repair. PMID- 20354745 TI - Spontaneous mesh evacuation per rectum after incisional ventral hernia repair. AB - We present a case of a 58-year-old man who was admitted to our hospital because of abdominal pain. He underwent incisional ventral hernia repair with intraabdominal mesh (ePTFE). On the day of admission, physical examination included the discovery of a foreign body in the rectum. There were no signs of acute abdomen. We induced stool, and the mesh came out with it. His further course was uneventful. Gastrografin series showed persisting fistula between the small intestine and colon, but without extralumination into the peritoneal cavity. The patient was discharged in good health and without signs of incisional ventral hernia. PMID- 20354743 TI - Quantitative trait locus on chromosome X affects bone loss after maturation in mice. AB - Genetic programming is known to affect the peak bone mass and bone loss after maturation. However, little is known about how polymorphic genes on chromosome X (Chr X) modulate bone loss after maturation. We previously reported a quantitative trait locus (QTL) on Chr X, designated Pbd3, which had a suggestive linkage to bone mass, in male SAMP2 and SAMP6 mice. In this study, we aimed to clarify the effects of Pbd3 on the skeletal phenotype. We generated a congenic strain, P2.P6-X, carrying a 45.6-cM SAMP6-derived Chr X interval on a SAMP2 genetic background. The effects of Pbd3 on the bone phenotype were determined by microcomputed tomography (microCT), whole-body dual-energy X-ray absorptiometry (DXA), serum bone turnover markers, and histomorphometric parameters. Both the bone area fraction (BA/TA) on microCT and whole-body DXA revealed reduced bone loss in P2.P6-X compared with that in SAMP2. The serum concentrations of bone turnover markers at 4 months of age were significantly lower in P2.P6-X than in SAMP2, but did not differ at 8 months of age. These results were observed in female mice, but not in male mice. In conclusion, a QTL within a segregated 45.6 cM interval on Chr X is sex-specifically related to the rate of bone loss after maturation. PMID- 20354746 TI - Questionable association between a monoamine oxidase A promoter polymorphism and sudden infant death syndrome. PMID- 20354747 TI - Antibodies against oxidized low-density lipoprotein are associated with subclinical atherosclerosis in recent-onset rheumatoid arthritis. AB - Rheumatoid arthritis (RA) patients have increased mortality largely as a result of cardiovascular diseases (CVD) that cannot be explained by traditional risk factors, suggesting that systemic inflammation may accelerate atherosclerosis. We investigated the presence of subclinical atherosclerosis in early RA (<12 months) and the possible association of RA-related risk factors. Forty patients with early RA and 40 controls matched for age, sex, and traditional risk factors for CVD were selected. Carotid US examination, assay of lipogram, C-reactive protein (CRP), and oxidized low-density lipoprotein antibodies (OxLDL-ab) were done. RA patients had significantly higher carotid intima-media thickness (cIMT) values and more plaque than the control (P<0.001 and P=0.0122, respectively). CRP and OxLDL-ab were significantly higher in RA patients than controls. Traditional risk factors and RA-related risk factors (disease duration, DAS-28, duration of treatment with steroids, erythrocyte sedimentation rate, and CRP) as well as OxLDL and cIMT were significantly higher in RA with plaques compared to those without plaques. Regression analysis identified the age of patients, CRP, and OxLDL-ab as an independent risk factor associated with the presence of atherosclerosis. CONCLUSION: there is increased prevalence of carotid plaques in patients with recent-onset RA compared to matched controls. The accelerated atherosclerosis is predicted by age, CRP, and oxLDL-ab. The association of plaques with elevated CRP and OxLDL-ab support the hypothesis that chronic systemic autoimmune inflammatory process is probably a driving force for premature atherosclerosis. PMID- 20354748 TI - Behcet's disease: from East to West. AB - Behcet's disease (BD) is classified among vasculitides. There are actually five nationwide surveys of BD: Iran, Japan, China, Korea, and Germany. Among case series, four are on more than 200 cases (Turkey, Morocco, Tunisia, and UK). BD was classically seen around the Silk Route. Now, it is seen everywhere. The male to female ratios were, respectively (in nationwide surveys), 1.19, 0.98, 1.34, 0.63, and 1.40 to 1. The mean age at onset was 26.2, 35.7, 33.8, 29, and 26 years. Major manifestations were seen, respectively, in nationwide surveys: mucous membrane (oral aphthosis in 97%, 98%, 98%, 99%, and 98%; genital aphthosis in 65%, 73%, 76%, 83%, and 64%); skin manifestations (pseudo-folliculitis in 57%, N/A, 31%, N/A, and 62%; erythema nodosum in 22%, N/A, 38%, N/A, and 42%; ocular manifestations in 55%, 69%, 35%, 51%, and 53%). Minor manifestations were seen, respectively, in nationwide surveys: joint manifestations in 33%, 57%, 30%, 38%, and 53%; neurological manifestations in 9%, 11%, 6.5%, 4.6%, and 11%; gastrointestinal manifestations in 7%, 15.5%, 9%, 7.3%, and 12%; vascular involvement in 8.9%, 8.9%, 7.7%, 1.8%, and 13%; pulmonary manifestations in 0.3%, N/A, 2.2%, N/A, and 3.6%; cardiac manifestations in 0.5%, N/A, 4%, N/A, and 3.2%. Laboratory tests are not useful except the pathergy test, which was positive in 54%, 44%, N/A, 40%, and 34% of cases. ESR was normal in many patients. Diagnosis is based upon clinical manifestations. The International Criteria for Behcet's Disease (ICBD, 2006) may be of help, having a sensitivity of 98.2% and a specificity of 95.6% in Iranian patients. PMID- 20354750 TI - A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer. AB - BACKGROUND: Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer. PATIENTS AND METHODS: Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months. RESULTS: The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 +/- 1.0 vs. 0.95 +/- 0.9, respectively), and a larger proportion did not experience an on study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 +/- 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population. CONCLUSIONS: Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, potentially through its anticancer activity. PMID- 20354752 TI - A calcium-driven mechanochemical model for prediction of force generation in smooth muscle. AB - A new model for the mechanochemical response of smooth muscle is presented. The focus is on the response of the actin-myosin complex and on the related generation of force (or stress). The chemical (kinetic) model describes the cross bridge interactions with the thin filament in which the calcium-dependent myosin phosphorylation is the only regulatory mechanism. The new mechanical model is based on Hill's three-component model and it includes one internal state variable that describes the contraction/relaxation of the contractile units. It is characterized by a strain-energy function and an evolution law incorporating only a few material parameters with clear physical meaning. The proposed model satisfies the second law of thermodynamics. The results of the combined coupled model are broadly consistent with isometric and isotonic experiments on smooth muscle tissue. The simulations suggest that the matrix in which the actin-myosin complex is embedded does have a viscous property. It is straightforward for implementation into a finite element program in order to solve more complex boundary-value problems such as the control of short-term changes in lumen diameter of arteries due to mechanochemical signals. PMID- 20354751 TI - Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings. AB - BACKGROUND: Thymidine kinase 1 in serum (STK1) has been found to be a reliable proliferation marker in clinical trials. In this study, we examined the significance of STK1 in routine clinical settings. METHODS: The concentration of STK1 was determined by a sensitive dot blot ECL assay. The STK1 value was correlated to clinical stage and reactions and used for monitoring the outcome of surgery and/or multidrug chemotherapy of 1,247 patients with five different types of carcinomas (lung, esophagus, gastric, head and neck, and thyroid) in routine clinical settings. RESULTS: The STK1 values correlated with the clinical stage in patients with lung, esophagus, thyroid, and gastric carcinomas. After treatment, STK1 declined in all tumor groups after treatments (P < 0.01). The STK1 was low (<2 pM) or decreasing during treatment in patients with clinical reactions of complete response (CR) or partial response (PR), but high (>2 pM) or increasing in patients with stable disease (SD) or progressive disease (PD), some of them showing metastasis. STK1 also reflected the differences in clinical reactions when surgery and chemotherapy were compared. CONCLUSION: We concluded that the concentration of TK1 in serum correlates to clinical stages and clinical reactions and monitors the effect of tumor therapies, not only in controlled clinical trials, but also in routine clinical settings. PMID- 20354753 TI - Microstructural and biomechanical alterations of the human aorta as a function of age and location. AB - While it is known that the aorta stiffens with location and age, little is known about the underlying mechanisms that govern these alterations. The purpose of this study was to investigate the relationship between the anisotropic biomechanical behavior and extracellular matrix microstructure of the human aorta and quantify how each changes with location and age. A total of 207 specimens were harvested from 5 locations (ascending n = 33, arch n = 38, descending n = 54, suprarenal n = 52, and abdominal n = 30) of 31 autopsy donor aortas (aged 3 days to 93 years). Each specimen underwent planar biaxial testing in order to derive quantitative biomechanical endpoints of anisotropic stiffness and compliance. Quantitative measures of fiber alignment and degree of fiber alignment were also generated on the same samples using a small-angle light scattering (SALS) technique. Circumferential and axial stiffening occurred with age and increased from the proximal to distal aorta, and the abdominal region was found to be more stiff than all others (p <= 0.006). Specimens from donors aged 61 and above were drastically more stiff than younger specimens (p < 0.001) and demonstrated greater circumferential compliance and axial stiffening (p < 0.001). Fiber direction for all ages and locations was predominantly circumferential (p < 0.001), and the degree of fiber alignment was found to increase with age (p < 0.001). Our results demonstrate that the aorta becomes more biomechanically and structurally anisotropic after age 60; with significant changes occurring preferentially in the abdominal aorta, these changes may play an important role in the predisposition of disease formation (e.g., aneurysm) in this region with age. PMID- 20354755 TI - Ontology-assisted analysis of Web queries to determine the knowledge radiologists seek. AB - Radiologists frequently search the Web to find information they need to improve their practice, and knowing the types of information they seek could be useful for evaluating Web resources. Our goal was to develop an automated method to categorize unstructured user queries using a controlled terminology and to infer the type of information users seek. We obtained the query logs from two commonly used Web resources for radiology. We created a computer algorithm to associate RadLex-controlled vocabulary terms with the user queries. Using the RadLex hierarchy, we determined the high-level category associated with each RadLex term to infer the type of information users were seeking. To test the hypothesis that the term category assignments to user queries are non-random, we compared the distributions of the term categories in RadLex with those in user queries using the chi square test. Of the 29,669 unique search terms found in user queries, 15,445 (52%) could be mapped to one or more RadLex terms by our algorithm. Each query contained an average of one to two RadLex terms, and the dominant categories of RadLex terms in user queries were diseases and anatomy. While the same types of RadLex terms were predominant in both RadLex itself and user queries, the distribution of types of terms in user queries and RadLex were significantly different (p < 0.0001). We conclude that RadLex can enable processing and categorization of user queries of Web resources and enable understanding the types of information users seek from radiology knowledge resources on the Web. PMID- 20354754 TI - Stunt or elongate? Two opposite strategies by which rice adapts to floods. AB - Expansion of habitat is important for the perpetuation of species. In particular, plants which are sedentary must evolve specialized functions to adapt itself to new environment. Deepwater rice is cultivated mainly in the lowland areas of South and Southeast Asia that are flooded during the rainy season. The internodes of deepwater rice elongates in response to increasing water level to keep its leaves above the water surface and avoid anoxia. This elongation is stimulated by ethylene-regulated genes, Snorkel1 and Snorkel2. In contrast, when a flash flood occurs at the seedling stage, submergence-tolerant rice, which carries Submergence-1A, remains stunted and survives in water for a few weeks to avoid the energy consumption associated with plant elongation, and restarts its growth using its conserved energy after the water recedes. Interestingly, both Snorkel genes and Submergence-1A encode ethylene-responsive factor-type transcription factor and are connected to gibberellin biosynthesis or signal transduction. However, deepwater and submergence-tolerant rice seem to have opposite flooding response; namely, escape by elongation or remain stunted under water until flood recedes. PMID- 20354756 TI - Sensitivity and specificity of a CAD solution for lung nodule detection on chest radiograph with CTA correlation. AB - The objective of this research was to determine the sensitivity and specificity of a commercially available computer-aided detection (CAD) system for detection of lung nodule on posterior-anterior (PA) chest radiograph in a varied patient population who are referred to computed tomographic angiogram (CTA) of the chest as a reference standard. Patients who had a PA chest radiograph with concomitant CTA of the chest were included in this retrospective study. The PA chest radiograph was analyzed by a CAD device, and results were recorded. A qualitative assessment of the CAD results was performed using a 5-point Likert scale. The CTA was then reviewed to determine if there were correlative nodules. The presence of a correlative nodule between 0.5 cm and 1.5 cm was considered a positive result. The baseline sensitivity of the system was determined to be 0.707 (95% CI = 0.52 0.86), with a specificity of 0.50 (95% CI = 0.38-0.76). Positive predictive value was 0.30 (95% CI = 0.24-0.49), with a negative predictive value of 0.858 (95% CI = 0.82-0.95), and accuracy of 0.555 (95% CI = 0.40-0.66). When excluding nodules that were qualitatively determined by a thoracic radiologist to be false positives, the specificity was 0.781 (95% CI = 0.764-0.839), the positive predictive value was 0.564 (95% CI = 0.491-0.654), the negative predictive value was 0.829 (95% CI = 0.819-0.878), and the accuracy was 0.737 (95% CI = 0.721 0.801). The use of CAD for lung nodule detection on chest radiograph, when used in conjunction with an experienced radiologist, has a very good sensitivity, specificity, and accuracy. PMID- 20354757 TI - Global pathogen distributions: a win-win for disease ecology and biogeography. PMID- 20354749 TI - Identification and analysis of muscle-related protein isoforms expressed in the white muscle of the mandarin fish (Siniperca chuatsi). AB - To identify muscle-related protein isoforms expressed in the white muscle of the mandarin fish Siniperca chuatsi, we analyzed 5,063 high-quality expressed sequence tags (ESTs) from white muscle cDNA library and predicted the integrity of the clusters annotated to these genes and the physiochemical properties of the putative polypeptides with full length. Up to about 33% of total ESTs were annotated to muscle-related proteins: myosin, actin, tropomyosin/troponin complex, parvalbumin, and Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCa). Thirty-two isoforms were identified and more than one isoform existed in each of these proteins. Among these isoforms, 14 putative polypeptides were with full length. In addition, about 2% of total ESTs were significantly homologous to "glue" molecules such as alpha-actinins, myosin-binding proteins, myomesin, tropomodulin, cofilin, profilin, twinfilins, coronin-1, and nebulin, which were required for the integrity and maintenance of the muscle sarcomere. The results demonstrated that multiple isoforms of major muscle-related proteins were expressed in S. chuatsi white muscle. The analysis on these isoforms and other proteins sequences will greatly aid our systematic understanding of the high flexibility of mandarin fish white muscle at molecular level and expand the utility of fish systems as models for the muscle genetic control and function. PMID- 20354758 TI - Radiation-induced cerebellar high-grade glioma accompanied by meningioma and cavernoma 29 years after the treatment of medulloblastoma: a case report. AB - Here, we report the case of a patient with cerebellar high-grade glioma that developed after the patient underwent treatment for medulloblastoma. A 34-year old man visited our hospital with complaints of dizziness and truncal ataxia. Magnetic resonance image showed a cerebellar tumor with multiple cavernomas and two lesions that were suspected to be meningiomas. The cerebellar tumor was surgically removed. According to pathological examination, the tumor was a high grade glioma that was positive for methylated O-6-methylguanine-DNA methyltransferase promoter. In the past, he had received radiotherapy at the age of 5, after which he was operated for desmoplastic medulloblastoma in his right cerebellar hemisphere. Seven years after the initial therapy, cavernoma-induced intracerebral hemorrhage of the right temporal lobe was noted. To our knowledge, this is the first case of radiation-induced double intracranial tumors accompanied by symptomatic cavernoma. PMID- 20354759 TI - Enhanced production of ethanol from glycerol by engineered Hansenula polymorpha expressing pyruvate decarboxylase and aldehyde dehydrogenase genes from Zymomonas mobilis. AB - To improve production of ethanol from glycerol, the methylotrophic yeast Hansenula polymorpha was engineered to express the pdc and adhB genes encoding pyruvate decarboxylase and aldehyde dehydrogenase II from Zymomonas mobilis, respectively, under the control of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter. The ethanol yield was 3.3-fold higher (2.74 g l(-1)) in the engineered yeast compared with the parent strain (0.83 g l(-1)). Further engineering to stimulate glycerol utilization in the recombinant strain via expression of dhaD and dhaKLM genes from Klebsiella pneumoniae encoding glycerol dehydrogenase and dehydroxyacetone kinase, respectively, resulted in a 3.7-fold increase (3.1 g l(-1)) in ethanol yield. PMID- 20354760 TI - Association between percutaneous coronary intervention and long-term C-reactive protein levels in patients with acute coronary syndromes. AB - C-reactive protein (CRP) is an independent predictor of risk in ACS patients, and it has been previously shown that percutaneous coronary intervention (PCI) is associated with an early rise in CRP. To assess the long-term relationship between PCI and CRP, we compared CRP levels at baseline, 30 days, 4 months and 24 months among patients in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial who were treated with PCI and those who did not receive PCI. At study entry, CRP was significantly higher among patients who had undergone PCI (13.2 vs. 9.5 mg/l, P < 0.001). However, by day 30 CRP was significantly lower among patients who had undergone PCI for management of the index event (1.5 vs. 2.1 mg/l, P < 0.001) and remained lower at 4 months and by end of study (average 2 years after ACS). Using a multivariable model, we observed that PCI was associated with 8.6% lower CRP level at month 4 (P = 0.05) and 14.2% at approximately 2 years (P = 0.0028). These analyses suggest that although PCI may acutely increase inflammation, it may also serve a role in decreasing inflammation associated with atherosclerotic plaques via long term mechanical stabilization. PMID- 20354761 TI - Heavy metal poisoning: the effects of cadmium on the kidney. AB - The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention. PMID- 20354762 TI - Oxidant/anti-oxidant dynamics in patients with advanced cervical cancer: correlation with treatment response. AB - Cervical cancer is the most common cancer in Indian women. Oxidative stress is potentially harmful to cells and ROS are involved in multistage carcinogenesis, in initiation and promotion. The aim was to study the alterations in the circulating pro-/anti-oxidants in advanced cervical cancer patients, before and after neoadjuvant chemoradiation and to assess the relevance of the variation in the levels to therapeutic response. 90 patients with advanced cancer cervix (FIGO IIIa-IVa) and 90 healthy controls were enrolled. Blood samples were collected: before and after chemotherapy, after radiation and after 1 year on follow-up. Pro /anti-oxidant levels were estimated using standard methods. Response to therapy was assessed during and after therapy and after 1 year of follow-up. The pre treatment levels of plasma lipid peroxide were significantly elevated; while antioxidant levels were lowered in cancer patients; when compared to controls. After chemotherapy, lipid peroxidation showed a significant decline in complete responders, as compared with partial/non-responders and remained highly significant after therapy and during follow-up. Anti-oxidant enzymes showed a mild increase (P < 0.05), after chemotherapy in complete responders, as compared with partial/non-responders and remained highly significant after therapy and on follow-up. This important finding suggests that pre-treatment levels of antioxidant-oxidant parameters and the extent of their change during treatment can predict the therapeutic response to neoadjuvant chemoradiation in advanced cancer cervix. Oxidant-antioxidant profile merits investigation as markers of response, survival, and recurrence in larger prospective studies, which might throw light on their possible use as predictors of chemoradiosensitivity of cervical tumors. PMID- 20354763 TI - Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis. AB - Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer. PMID- 20354765 TI - Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. AB - PURPOSE: The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration. METHODS: Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels. RESULTS: Delivery of proteins using microneedles resulted in faster systemic availability, measured via t(max,) and increased maximal drug concentration, C(max,) over SC delivery for all proteins tested. Some agents also exhibited increased bioavailability for the ID route. Imaging studies using reporter dyes showed rapid lymphatic-mediated uptake. CONCLUSIONS: Microneedle delivery is applicable to a wide variety of protein drugs and is capable of effective parenteral administration of therapeutic drug dosages. This delivery route alters absorption kinetics via targeting a tissue bed better perfused with lymphatic and blood vessels than the SC space. Microneedle delivery may afford various advantages, including a robust method to increase the absorption rate and bioavailability of proteins that have been challenging to deliver at therapeutic levels or with physiologically relevant profiles. PMID- 20354764 TI - Nrf2-Keap1 signaling as a potential target for chemoprevention of inflammation associated carcinogenesis. AB - Persistent inflammatory tissue damage is causally associated with each stage of carcinogenesis. Inflammation-induced generation of reactive oxygen species, reactive nitrogen species, and other reactive species not only cause DNA damage and subsequently mutations, but also stimulate proliferation of initiated cells and even metastasis and angiogenesis. Induction of cellular cytoprotective enzymes (e.g., heme oxygenase-1, NAD(P)H:quinone oxidoreductase, superoxide dismutase, glutathione-S-transferase, etc.) has been shown to mitigate aforementioned events implicated in inflammation-induced carcinogenesis. A unique feature of genes encoding these cytoprotective enzymes is the presence of a cis acting element, known as antioxidant response element (ARE) or electrophile response element (EpRE), in their promoter region. A stress-responsive transcription factor, nuclear factor erythroid-2-related factor-2 (Nrf2), initially recognized as a key transcriptional regulator of various cytoprotective enzymes, is known to play a pivotal role in cellular defense against inflammatory injuries. Activation of Nrf2 involves its release from the cytosolic repressor Kelch-like ECH-associated protein-1 (Keap1) and subsequent stabilization and nuclear localization for ARE/EpRE binding. Genetic or pharmacologic inactivation of Nrf2 has been shown to abolish cytoprotective capability and to aggravate experimentally induced inflammatory injuries. Thus, Nrf2-mediated cytoprotective gene induction is an effective strategy for the chemoprevention of inflammation associated carcinogenesis. PMID- 20354766 TI - Formation and closure of microchannels in skin following microporation. AB - PURPOSE: To characterize the microchannels created in hairless rat skin by microneedles and investigate their closure following exposure to different occlusive conditions. METHODS: Maltose microneedles were characterized by scanning electron microscopy. The microchannels created and their closure when exposed to different conditions was investigated using a variety of techniques. RESULTS: Microscopic imaging indicates a pyramidal geometry of maltose microneedles with an average length of 559 +/- 14 MUm and tip radius of 4 MUm. Upon insertion into skin, they created microchannels with an average surface diameter of 60 MUm and an average depth of 160 +/- 20 MUm as observed by histological sectioning and confocal microscopy. Skin recovers its barrier function within 3-4 hrs, and microchannels closed within 15 hrs of poration when exposed to environment. However, when occluded, the microchannels remained open for up to 72 hrs in vivo, as observed by calcein imaging, transepidermal water loss measurements and methylene blue staining. CONCLUSION: Maltose microneedles penetrated the stratum corneum barrier and created microchannels in skin which completely close within 15 hrs after poration. However, under occluded conditions, barrier recovery can be delayed for up to 72 hrs in vivo. PMID- 20354767 TI - Nanoparticles for local drug delivery to the oral mucosa: proof of principle studies. AB - PURPOSE: To determine if solid lipid nanoparticles represent a viable strategy for local delivery of poorly water soluble and unstable chemopreventive compounds to human oral tissues. METHODS: Nanoparticle uptake and compound retention evaluations employed monolayer-cultured human oral squamous cell carcinoma (OSCC) cell lines and normal human oral mucosal explants. Feasibility of nanoparticle delivery was also evaluated with respect to the presence of phase-III efflux transporters in normal oral mucosal tissue and OSCC tissues. RESULTS: Functional uptake assays confirmed significantly greater internalization of nanoparticle delivered fluorescent probe relative to free-fluorescent probe delivery, while concurrently demonstrating nanoparticle uptake rate differences among the OSCC cell lines and the phagocytic control human monocyte cell line. Mucosal explants exhibited nanoparticle penetration and internalization in the spinous and basal epithelial layers (7/10 specimens), and also exhibited the presence of the phase III efflux transporters multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). CONCLUSIONS: These data confirm nanoparticle internalization by OSCC cells and support the premise that nanoparticle-based delivery provides higher final intracellular levels relative to bolus administration. Furthermore, the penetration and subsequent internalization of nanoparticles within the proliferating basal layer cells demonstrates the feasibility of nanoparticle formulations for local delivery and stabilization of oral chemopreventive compounds. PMID- 20354768 TI - The contribution of different formulation components on the aerosol charge in carrier-based dry powder inhaler systems. AB - PURPOSE: To measure aerosol performance of a lactose carrier/salbutamol sulphate powder blend and identify contributions of non-formulation and formulation components on the resulting aerosol charge. METHODS: A 67.5:1 (%w/w) blend of 63 90 microm lactose with salbutamol sulphate, and lactose alone (with and without the blending process), was dispersed from a Cyclohaler into the electrical Next Generation Impactor at 30, 60 and 90 L/min. Mass and charge profiles were measured from each dispersion, as a function of impactor stage. The charge profile from an empty capsule in the Cyclohaler was also studied. RESULTS: Lactose deposition from the blend was significantly greater, and net charge/mass ratios were smaller, in the pre-separator compared to formulations without drug. Fine particle fraction of salbutamol sulphate increased with flow rate (9.2 +/- 2.5% to 14.7 +/- 2.7%), but there was no change in net charge/mass ratio. The empty capsule produced a cycle of alternating net positive and negative discharges ( approximately 200 pC to 4 nC). CONCLUSIONS: Capsule charge can ionize surrounding air and influence net charge measurements. Detachment of fine drug during aerosolisation may reduce net specific charge and lead to increased lactose deposition in the pre-separator. Increase in FPF may be due to increased force of detachment rather than electrostatic forces. PMID- 20354769 TI - Isolation and characterization of cetirizine degradation product: mechanism of cetirizine oxidation. AB - PURPOSE: The goal of the study was to isolate and analyze a cetirizine degradation product, formed within a PEG-containing formulation and to elucidate the mechanism of oxidation of cetirizine. METHODS: Cetirizine, formulated in PEG containing matrix, was subjected to forced degradation conditions in the pH range from 3 to 10, and the product was analyzed by HPLC and LC-MS/MS. Additionally, pure cetirizine was subjected to selective oxidization by hydrogen peroxide and sodium percarbonate. The reaction mixture was purified, and the isolated material was analyzed by (1)H NMR. RESULTS: Oxidation process was investigated in order to model the degradation of cetirizine in PEG-containing formulation. Site of oxidation is proposed based on correlation of the results of forced degradation with ionization scheme of cetirizine. The finding was verified by spiking of cetirizine degradation sample with cetirizine N-oxide reference standard. CONCLUSIONS: Degradation of cetirizine in polyethylene glycol arose from the reaction between the drug and the reactive peroxide intermediates such as peroxyl radicals formed through oxidation of PEG. Selective oxidation of cetirizine and isolation/characterization of the oxidation product allowed the identification of the oxidation product as cetirizine N-oxide. The mechanism of oxidation is proposed. PMID- 20354770 TI - FoxM1 is a novel target of a natural agent in pancreatic cancer. AB - PURPOSE: Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and/or treatment are urgently needed. Genistein has been found to be responsible for lowering the rate of pancreatic cancer. However, the molecular mechanisms by which genistein elicits its effects on pancreatic cancer cells has not been fully elucidated. Therefore, the purpose of the current study was to elucidate the anti cancer mechanism(s) of genistein. METHODS: Multiple molecular techniques, such as Real-time RT-PCR, Western blot analysis, invasion assay, immunofluorescence assay, gene transfection, MTT assay, and Histone/DNA ELISA, were used. RESULTS: We found that genistein inhibited cell growth accompanied by induction of apoptosis with concomitant attenuation of FoxM1 and its downstream genes, such as survivin, cdc25a, MMP-9, and VEGF, resulting in the inhibition of pancreatic cancer cell invasion. We also found that down-regulation of FoxM1 by siRNA prior to genistein treatment resulted in enhanced cell growth inhibition and induction of apoptosis. CONCLUSION: This is the first report showing the molecular role of FoxM1 in mediating the biological effects of genistein in pancreatic cancer cells, suggesting that FoxM1 could be a novel target for the treatment of pancreatic cancer. PMID- 20354772 TI - The standard strong ion difference, standard total titratable base, and their relationship to the Boston compensation rules and the Van Slyke equation for extracellular fluid. AB - A general formalism for calculating physiological acid-base balance in multiple compartments is extended to the combined interstitial, plasma, and erythrocyte multicompartment system in humans using the Siggaard-Andersen approximation for interstitial fluid. The resulting equations for total titratable base and strong ion difference reproduce the experimental in vivo carbon dioxide titration curve as well as the experimental strong ion difference value of the interstitial, plasma, and erythrocyte system in normal man. The "Boston rules" for compensation in acute respiratory acidosis and alkalosis are then derived analytically from the model. The Van Slyke equation for the interstitial, plasma, and erythrocyte system is also derived and shown to approximate the Van Slyke equation for standard base excess. PMID- 20354773 TI - A resonance Raman band assignable to the O-O stretching mode in the resting oxidized state of bovine heart cytochrome c oxidase. AB - In the resting oxidized state (the fully oxidized "as-isolated" state) of cytochrome c oxidase (CcO) preparation, a resonance Raman band is observed at 755 cm(-1) upon 647.1 nm excitation in resonance with an absorption band at 655 nm. Addition of cyanide eliminates the Raman band concomitant with loss of the absorption band at 655 nm. These results strongly suggest that the Raman band at 755 cm(-1) originates from the O-O stretching mode of the bridging peroxide (Fe O(-)-O(-)-Cu) in the O(2) reduction site of the fully oxidized "as-isolated" CcO. Although the peroxide bridged structure has been proposed on the basis of X-ray crystallography and reductive titration experiments, the present vibrational spectroscopic analyses reveal conclusively the chemical nature of the bridging ligand at the O(2) reduction site of the fully oxidized "as-isolated" bovine heart CcO. PMID- 20354771 TI - Epithelial-mesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer. AB - There is increasing support for the hypothesis that most tumors contain a subpopulation of cells, referred to here as tumor initiating cells (TICs), with the ability to self-renew and to regenerate all the cell types within the tumor. TICs are enriched in breast cancer patients after common treatments, indicating their intrinsic therapeutic resistance. Two independently-derived gene transcription "signatures" of TICs from different studies indicate enrichment of TICs within the recently-identified "claudin-low" intrinsic molecular subtype of breast cancer. These are characterized by high expression of markers associated with epithelial-mesenchymal transition (EMT), suggesting that claudin-low cells may arise from more immature stem or progenitor cells than other breast cancers. EMT is a process by which cells acquire molecular alterations that facilitate dysfunctional cell-cell adhesive interactions and junctions, as well as a more spindle-shaped morphology. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Induction of EMT in immortalized human mammary epithelial cells results in an increased ability to form mammospheres, and in the expression of stem cell and TIC markers, suggesting that there may be a direct link between the EMT and the gain of TIC properties. Targeting specific molecular pathways-such as Notch, Wnt, and TGFss-associated with development and EMT in the TIC subpopulation, in addition to conventional chemo- and radiation therapies that target the bulk tumor, may ultimately provide a more effective strategy in treating breast cancer. Here, we review recent evidence of the involvement of EMT in breast cancer TICs, focusing on clinical studies. PMID- 20354775 TI - Is sensation seeking a stable trait or does it change over time? AB - The theory of sensation seeking has conceptualized this construct as a stable personality trait associated with a variety of problem behaviors. Reckless behavior theory posits that increases in reckless behavior during adolescence can be attributed, in part, to increases in sensation seeking. This study evaluated patterns of stability and change in sensation seeking among 868 urban, minority youth (53% female), followed longitudinally across middle school (6th-8th grades). Group-based trajectory analysis identified a stable low group (20%), a moderate increasing group (60%), and a stable high group (20%) each of which demonstrated unique associations with changes in problem behaviors. Stable low sensation seekers reported consistently low levels of aggression, delinquency, and substance use across middle school. Moderate increasing sensation seekers reported significant increases in these risk behaviors over time from levels near zero in the 6th grade. Stable high sensation seekers reported high, stable levels of aggression and delinquency upon entry into middle school as well as significant increases in substance use across middle school. These results lend support to both theories and highlight a need for caution when categorizing adolescents as high or low sensation seekers. PMID- 20354774 TI - Probing the effect of transport inhibitors on the conformation of the mitochondrial citrate transport protein via a site-directed spin labeling approach. AB - The present investigation utilized the site-directed spin labeling method of electron paramagnetic resonance (EPR) spectroscopy to identify the effect of citrate, the natural ligand, and transport inhibitors on the conformation of the yeast mitochondrial citrate transport protein (CTP) reconstituted in liposomal vesicles. Spin label was placed at six different locations within the CTP in order to monitor conformational changes that occurred near each of the transporter's two substrate binding sites, as well as at more distant domains within the CTP architecture. We observed that citrate caused little change in the EPR spectra. In contrast the transport inhibitors 1,2,3-benzenetricarboxylate (BTC), pyridoxal 5'-phosphate (PLP), and compound 792949 resulted in spectral changes that indicated a decrease in the flexibility of the attached spin label at each of the six locations tested. The rank order of the immobilizing effect was compound 792949 > PLP > BTC. The four spin-label locations that report on the CTP substrate binding sites displayed the greatest changes in the EPR spectra upon addition of inhibitor. Furthermore, we found that when compound 792949 was added vectorially (i.e., extra- and/or intra-liposomally), the immobilizing effect was mediated nearly exclusively by external reagent. In contrast, upon addition of PLP vectorially, the effect was mediated to a similar extent from both the external and the internal compartments. In combination our data indicate that: i) citrate binding to the CTP substrate binding sites does not alter side chain and/or backbone mobility in a global manner and is consistent with our expectation that both in the absence and presence of substrate the CTP displays the flexibility required of a membrane transporter; and ii) binding of each of the transport inhibitors tested locked multiple CTP domains into more rigid conformations, thereby exhibiting long-range inter-domain conformational communication. The differential vectorial effects of compound 792949 and PLP are discussed in the context of the CTP homology-modeled structure and potential mechanistic molecular explanations are given. PMID- 20354776 TI - A comparison of the development of audiovisual integration in children with autism spectrum disorders and typically developing children. AB - This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7-16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability. Results showed that the children with ASD were delayed in visual accuracy and audiovisual integration compared to the control group. However, in the audiovisual integration measure, children with ASD appeared to 'catch-up' with their typically developing peers at the older age ranges. The suggestion that children with ASD show a deficit in audiovisual integration which diminishes with age has clinical implications for those assessing and treating these children. PMID- 20354777 TI - In the absence of marriage: long-term concurrent partnerships, pregnancy, and HIV risk dynamics among South African young adults. AB - In KwaZulu/Natal, South Africa, where HIV prevalence is among the world's highest, a longitudinal qualitative study of partnership dynamics and HIV preventive behaviors was conducted. 47 young adults aged 18-24 participated in in depth interviews, and 29 were re-interviewed 2 years later. Five analytical domains emerged: primary partnerships, love and romance; secondary partnerships; pregnancy/parenthood; condom use/prevention; and contextual influences, including schooling and future aspirations. Primary relationships were long-lasting, with most men and women in the same relationship at 2-year follow-up. Secondary, casual partnerships were common for men and women, although these were shorter and changed frequently. Love and marriage aspirations were not viewed as incompatible with secondary partners. Condom use increased over time in some primary relationships, but decreased in others, and was nearly universal with non primary partners. Pregnancy, school drop-out, and economic need strongly influence young people's lifecourse. These findings suggest the need to focus prevention efforts on the partnership context, including partner reduction, and structural factors that impede or enhance prevention success. PMID- 20354778 TI - Assessment of evidence-based psychotherapy practices in usual care: challenges, promising approaches, and future directions. PMID- 20354779 TI - The androgen receptor in breast cancer: learning from the past. PMID- 20354780 TI - Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine resistant breast cancer cells and improves endocrine response in endocrine sensitive cells. AB - Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 MUM, 0.05 MUM and 0.13 MUM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 MUM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment. PMID- 20354781 TI - Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision. AB - Nipple discharge (ND) is a common symptom seen in breast cancer clinics. The primary aim of this study was to identify preoperative risk factors for breast cancer in patients with pathologic ND. The secondary aim was to assess the clinical and pathological effectiveness of physical examination, galactography, cytological examination of the discharge, selective duct excision and ductoscopy. All patients operated on between 1975 and 2008 who presented with ND as their only symptom was analyzed. Discharge's characteristics, cytological data and galactography reports were recorded. The relationship between each individual finding and the risk of breast cancer was calculated. For each diagnostic tool, the sensitivity, specificity and complication rates were calculated and compared. Nine-hundred-fifteen patients underwent selective duct excision. Two-hundred nineteen patients (23.9%) were found to be affected by carcinoma. In 100/330 (30.3%) patients with bloody discharge and in 42/239 (17.6%) patients with serous secretion cancer was detected (P = 0.004, P = 0.013, respectively). Patients with sero-sanguinous or coloured discharge had the same risk of cancer as the population analyzed (23.9%, P = NS). Galactographic finding of irregular stenosis seemed to be associated with a higher risk of cancer (P = 0.0001). Cytological findings C5 and C4 were associated with cancer (P = 0.001). Selective duct excision showed highest sensitivity and specificity. In conclusion, the well established role of bloody secretion is confirmed. The supposed benign aetiology of serous, coloured or sero-sanguinous discharge is questionable. The high specificity of the cytological exam justifies routine examination of the ND. Selective duct excision can be considered as the diagnostic gold-standard. PMID- 20354782 TI - Mineral compositions and sources of the riverbed sediment in the desert channel of Yellow River. AB - The Yellow River flows through an extensive, aeolian desert area and extends from Xiaheyan, Ningxia Province, to Toudaoguai, Inner Mongolia Province, with a total length of 1,000 km. Due to the construction and operation of large reservoirs in the upstream of the Yellow River, most water and sediment from upstream were stored in these reservoirs, which leads to the declining flow in the desert channel that has no capability to scour large amount of input of desert sands from the desert regions. By analyzing and comparing the spatial distribution of weight percent of mineral compositions between sediment sources and riverbed sediment of the main tributaries and the desert channel of the Yellow River, we concluded that the coarse sediment deposited in the desert channel of the Yellow River were mostly controlled by the local sediment sources. The analyzed results of the Quartz-Feldspar-Mica (QFM) triangular diagram and the R-factor models of the coarse sediment in the Gansu reach and the desert channel of the Yellow River further confirm that the Ningxia Hedong desert and the Inner Mongolian Wulanbuhe and Kubuqi deserts are the main provenances of the coarse sediment in the desert channel of the Yellow River. Due to the higher fluidity of the fine sediment, they are mainly contributed by the local sediment sources and the tributaries that originated from the loess area of the upper reach of the Yellow River. PMID- 20354783 TI - Hydrogen-rich saline protects against spinal cord injury in rats. AB - In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF. PMID- 20354784 TI - Evaluation of aging on muscle blood flow in conscious healthy dogs by duplex Doppler ultrasonography. AB - According to a study conducted on a population of 9,248 subjects, cardiac diseases are the second most prevalent cause of death in the dog. During the last decades, a common scenario has been the increase on life expectancy of dogs. The exact relationship between the negative modifications of cardiovascular function and the development of specific cardiovascular diseases is difficult to ascertain, and also, the effect of age per se on vascular impedance is important. It may result in limited cardiovascular reserve under conditions of increase demand in senescent animals. To evaluate the effect of age on the peripheral vasculature specifically, the objective of this study was to compare parameters of the regional blood flow as well as compliance and resistance indexes in the femoral arterial system of younger and older conscious healthy dogs by duplex Doppler ultrasonography. The data were collected from 16 mixed-breed dogs divided into two groups: young and old healthy dogs. In all dogs Doppler spectra blood flow patterns of the femoral artery were triphasic. Significant differences were not found between the parameters measured for young and old groups. Despite this, the average value of femoral flow volume in the older group was approximately 50% lower than the younger group. This finding could play an important role in limiting exercise response with age. In order to validate these speculations, further studies should be performed in aged dogs. PMID- 20354785 TI - Synthesis of quinolone substituted pyrazoles, isoxazoles and pyridines as a potential blue luminophors. AB - Series of quinolone C(3)-substituted pyrazolines, isoxazolines, pyridines and pyrimidines were synthesized in good yields by the cyclocondensation reactions of 1, 2-unsaturated ketones and hydrazines, hydroxylamine hydrochloride and dimedone respectively. The quinolone derivatives (3, 5 and 7) were synthesized and further studied for their photophysical properties. High absorption and quantum yield are found for N(1)-phenyl and C(3,4)-dimethoxy substituents on phenyl ring (3h). Energy optimization by PM6 methods showed high stability required for selection of suitable candidates to be use as future blue emitters. PMID- 20354786 TI - Exposing viruses: RNA patterns sensed by RIG-I-like receptors. AB - INTRODUCTION: Virus infection triggers a multitude of innate immune pathways that limit viral replication, restrict viral spread and coordinate antigen-specific, adaptive immune responses. Type-I interferons (IFNs) play a crucial role in these events. Innate receptors expressed by the host cell recognize virus presence and signal for rapid IFN induction following infection. SCOPE: This review article discusses recent progress in our understanding of how cytoplasmic RIG-I-like receptors detect infection with RNA viruses. PMID- 20354787 TI - Pseudonocardia rhizophila sp. nov., a novel actinomycete isolated from a rhizosphere soil. AB - During the course of our research on new actinobacterial sources, a novel actinomycete strain YIM 67013(T) was isolated from rhizosphere soil of Tripterygium wilfordii Hook. f. collected from Yunnan province, south-west China. The strain formed well-differentiated aerial and substrate mycelia, grew in the presence of up to 15% NaCl (optimum, 0-3% NaCl). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 67013(T) belongs to the genus Pseudonocardia, with highest similarity to Pseudonocardia thermophila DSM 43832(T) (97.6%). Sequence similarities between strain YIM 67013(T) and the other Pseudonocardia species ranged from 96.6 to 93.2%. Key morphological and physiological characteristics as well as chemotaxonomic features of strain YIM 67013(T) were congruent with the description of the genus Pseudonocardia. The G+C content of the genomic DNA was 69.7 mol%. Based on comparative analysis of physiological, biochemical and chemotaxonomic data, including low DNA-DNA hybridization results, it is proposed that strain YIM 67013(T) represents a novel species of the genus Pseudonocardia, named Pseudonocardia rhizophila sp. nov. The type strain is YIM 67013(T) (= CCTCC AA 209043(T) = DSM 45381(T)). PMID- 20354788 TI - Access to children's medicines in the United Kingdom, Australia and New Zealand in 1998, 2002 and 2007. AB - OBJECTIVE: To describe the listing of prescription entities (unique active agents only available on prescription) in standard reference texts that were licensed for children (0-18 years), in dosage forms suitable for children, and subsidised (Government funded) for children. Setting The United Kingdom, Australia and New Zealand in 1998, 2002 and 2007. METHOD: A review of data from 1998, 2002, and 2007 using standard prescribing and subsidy reference sources in each country. The study examined all prescription entities, orally available entities, and entities newly licensed for children 2002-2007. MAIN OUTCOME MEASURE: Changes in the number of prescription entities that were licensed, suitably formulated and subsidised for children over the period. Results The United Kingdom had the highest number of prescription entities (1149 in 1998; 1049 in 2007), entities licensed for children (677; 564), entities suitably formulated for children (791; 676), and entities licensed for children and subsidised (677; 562) over the period. However, the numbers and proportions of entities licensed for children and suitably formulated for children decreased over the period of the study. New Zealand and Australia had lower numbers throughout the period, but the number of entities licensed for children (New Zealand 319-450, Australia 288-466) and entities licensed for children and subsidised (New Zealand 245-288, Australia 155 254) increased over the period. CONCLUSION: Over the period of the study, there was a decrease in listed prescription entities that were licensed for children in the United Kingdom, but an increase in Australia and New Zealand. There were considerably fewer entities licensed, suitably formulated and subsidised for children than for adults at all three time points and in all three countries. This reinforces the need for the current initiatives to improve access to medicines for children. PMID- 20354789 TI - The interrelationship between hypertension and blood pressure, attendance at religious services, and race/ethnicity. AB - The relationships between race/ethnicity and hypertension or blood pressure (BP), as well as frequency of religious services attendance and hypertension/BP are well documented. However, the association between these three factors is poorly understood. Using national data, this interrelationship was assessed in non Hispanic whites and blacks, and Mexican-Americans (n = 12,488). Compared to those who never attended services, whites who attended services weekly had lower odds of hypertension, as did blacks who attended more than weekly. There was no relationship between attendance and hypertension among Mexican-Americans. Attendance was inversely related to systolic BP for all groups, but more so for whites and blacks compared to Mexican-Americans. These results further demonstrate the benefits of increased attendance at religious services on hypertension/BP, but suggest that these benefits were not as advantageous for all. PMID- 20354790 TI - Self-forgiveness in psychology and psychotherapy: a critique. AB - This critique proposes that self-forgiveness is a misleading and inaccurate concept for understanding the conditions to which it is applied. Besides the fact that traditional religion provides no rationale for self-forgiveness, four specific criticisms are presented. (1) Self-forgiveness causes splitting of the self--creating various problems. (2) It involves a conflict of interest between the self that judges and the self that is judged. (3) Through its extreme emphasis on the self, it promotes narcissism and appeals to narcissists. (4) Research indicates that interpersonal forgiveness and self or intrapersonal forgiveness involve different psychological processes. We conclude that self acceptance is a more accurate and useful term for the process and benefits attributed to self-forgiveness. PMID- 20354792 TI - Effect of diet supplemented with quinoa seeds on oxidative status in plasma and selected tissues of high fructose-fed rats. AB - Oxidative stress plays an important role as a mediator of damage produced by fructose metabolism. This work was designed to investigate the effect of diet supplemented with quinoa seeds on oxidative stress in plasma, heart, kidney, liver, spleen, lung, testis and pancreas of fructose administered rats. Fructose administration (310 g/kg fodder for 5 weeks) caused oxidative stress that was manifested by the increase in plasma malondialdehyde (MDA) (p<0.05), and by the non-significant changes in the enzymatic antioxidant potential in plasma and most of tissues. Co-administration of quinoa seeds (310 g/kg fodder) maintained normal activities of some enzymes. It also influenced the oxidative stress as was evidenced by decreasing MDA in plasma, and decreasing the activities of antioxidant enzymes (erythrocyte superoxide dismutase - eSOD, catalase -CAT, plasma glutathione peroxidase - pGPX). These findings demonstrate that quinoa seeds can act as a moderate protective agent against potential of fructose induced changes in rats by reducing lipid peroxidation and by enhancing the antioxidant capacity of blood (plasma) and heart, kidney, testis, lung and pancreas. PMID- 20354791 TI - High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. AB - BACKGROUND: In Gaucher disease (GD), lysosomal glucocerebrosidase deficiency results in glucosylceramide accumulation in macrophage lysosomes. Hepatocytes do not accumulate glucosylceramide due in part to biliary secretion. Although gallstones (GS) occur in type 1 Gaucher disease (GD1), the chemical nature of stones, their association with metabolic parameters, and whether bile composition is altered are not understood. We assessed the prevalence of GS, their chemical composition, biliary lipids, and associated metabolic factors. METHODS: The study cohort comprised 417 patients comprehensively evaluated for GD1 severity. Ascertainment of GS, fasting lipoprotein profile, and bile lipid analyses were performed. RESULTS: The prevalence of GS in GD1 was 32%. Compared with men, the prevalence of GS was higher in women, increasing from 4.2% and 11.8% at age 20-29 years to 71% and 60% at age >70 years, respectively. Patients with GS were more likely to be asplenic (p < 0.0001), older (p < 0.0001), have higher low-density lipoprotein (LDL) cholesterol (p = 0.002), and more severe GD1 disease compared with those without GS. On multiple logistic regression analysis, factors associated with GS were age (p < 0.001), female sex (p = 0.03), and splenectomy (p = 0.005). Compared with the general population, prevalence of GS was approximately 5-fold higher. Bile lipid analyses revealed cholesterol stones in five patients and pigment stones in one. Bile lipid composition was abnormal and contained glucosylceramide. CONCLUSIONS: Our results point to a metabolic syndrome in GD1 consisting of a propensity to cholesterol GS, low high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and body mass index (BMI) associated with abnormal biliary lipid secretion. PMID- 20354793 TI - Pandemic ventilator rationing and appeals processes. AB - In a severe influenza pandemic, hospitals will likely experience serious and widespread shortages of patient pulmonary ventilators and of staff qualified to operate them. Deciding who will receive access to mechanical ventilation will often determine who lives and who dies. This prospect raises an important question whether pandemic preparedness plans should include some process by which individuals affected by ventilator rationing would have the opportunity to appeal adverse decisions. However, the issue of appeals processes to ventilator rationing decisions has been largely neglected in state pandemic planning efforts. If we are to devise just and effective plans for coping with a severe influenza pandemic, more attention to the issue of appeals processes for pandemic ventilator rationing decisions is needed. Arguments for and against appeals processes are considered, and some suggestions are offered to help efforts at devising more rational pandemic preparedness plans. PMID- 20354794 TI - A communitarian approach to public health. AB - This paper argues that there is a need to move yet further than has already been suggested by some from the individual to the collective as a base for public health. A communitarian approach is one way to achieve this. This has the advantage of allowing not only the community's voice to have a say in setting the values for public health but also more formally the development of a constitution on which public health might then be built. It also sees public health as a social institution which can be valued in its own right. PMID- 20354796 TI - Abstracts of the Official Proceedings of the 11th Annual Meeting of the American Society of Breast Surgeons. April 28-May 2, 2010. Las Vegas, Nevada, USA. PMID- 20354795 TI - Discriminative capacity of the EQ-5D, SF-6D, and SF-12 as measures of health status in population health survey. AB - PURPOSE: To compare the EQ-5D, SF-6D, and SF-12 in terms of their capacity to discriminate between groups defined by relevant socio-demographic and health characteristics in a general population survey. METHODS: Data were obtained from the 2006 Catalan Health Interview Survey, a representative sample (n = 4,319) of the general population of Catalonia (Spain). Effect sizes (ES) and Receiver Operating Characteristic (ROC) curves were calculated to evaluate the instruments' capacity to distinguish between groups based on socio-demographic variables, recent health problems, perceived health, psychological distress, and selected chronic conditions. RESULTS: All instruments showed a similar discriminative capacity between groups based on socio-demographic variables, recent medical visit (ES = 0.47-0.55), activity limitations (ES = 0.92-0.98), perceived health (ES = 0.97-1.33), and psychological well-being (ES = 1.17-1.57). Effect sizes between respondents with and without any of fourteen selected chronic conditions were large (0.76-1.04) for 4, moderate (0.55-0.74) for 8, and small (0.17-0.39) for two on the EQ-5D index. A similar pattern was observed for the SF-12 but ES were predominantly moderate (7 conditions) or small (6 conditions) on the SF-6D. CONCLUSIONS: The EQ-5D and SF-12 were largely comparable in estimating the health burden of chronic conditions, recent health problems, and social inequalities. The SF-6D was less sensitive than the EQ-5D index and SF-12, particularly for physical chronic conditions. PMID- 20354798 TI - Dermatofibrosarcoma protuberans: how wide should we resect? AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation. MATERIALS AND METHODS: Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1-2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes. RESULTS: A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1-84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1-4) with a median excision width of 2 cm (range 0.5-3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1-210), 2 patients (1%) with head and neck primaries recurred locally. CONCLUSIONS: Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities. PMID- 20354799 TI - Five reasons why cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy must be regarded as the new standard of care for diffuse malignant peritoneal mesotheliomia [corrected]. PMID- 20354800 TI - Enhanced detection of early hepatocellular carcinoma by serum SELDI-TOF proteomic signature combined with alpha-fetoprotein marker. AB - BACKGROUND: Biomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha fetoprotein (AFP) level in HCC diagnosis. PATIENTS AND METHODS: Serum samples were obtained from 120 HCC and 120 LC patients for biomarker discovery and validation studies. ProteinChip technology was employed for generating SELDI-TOF proteomic features and analyzing serum proteins/peptides. RESULTS: A diagnostic model was established by CART algorithm, which is based on 5 proteomic peaks with m/z values at 3324, 3994, 4665, 4795, and 5152. In the training set, the CART algorithm could differentiate HCC from LC subjects with a sensitivity and specificity of 98% and 95%, respectively. The results were assessed in blind validation using separate cohorts of 60 HCC and 60 LC patients, with an accuracy of 83% for HCC and 92% for LC patients. The diagnostic odd ratio (DOR) indicated that SELDI-TOF proteomic signature could achieve better diagnostic performance than serum AFP level at a cutoff of 20 ng/mL (AFP(20)) (92.72 vs 9.11), particularly superior for early-stage HCC (87% vs 54%). Importantly, a combined use of both tests could enhance the detection of HCC (sensitivity, 95%; specificity, 98%; DOR, 931). CONCLUSION: Serum SELDI-TOF proteomic signature, alone or in combination with AFP marker, promises to be a good tool for early diagnosis and/screening of HCC in at-risk population with liver cirrhosis. PMID- 20354801 TI - Extremity soft tissue sarcoma care in the elderly: insights into the generalizability of NCI Cancer Trials. AB - BACKGROUND: The projected increase in older persons in the United States, their underrepresentation in clinical trials, and the rarity of extremity soft tissue sarcomas (ESTS) limit our understanding of ESTS care in the elderly. We explored the extent of older age (> or =65 years) on patterns of ESTS care in NCI sponsored population-based dataset. MATERIALS AND METHODS: Using the 1991-2006 Surveillance Epidemiology and End Results registries, we identified 2586 Medicare aged persons > or =65 years with ESTS. We compared demographics, tumors, and treatments by age category. Multivariable analyses were used to examine the effect of older age on ESTS care and survival, adjusting for covariates. RESULTS: More than 30% of adult ESTS were diagnosed in patients older than 65 years. A significant trend was observed between increasing age and decreased use of sarcoma-directed surgery and delivery of radiotherapy after limb-sparing surgery for high-grade or T2 tumors. Limb amputation rates did not vary by age. However, both African-American (odds ratio [OR] 1.85, 95% confidence interval [95% CI] 1.05-3.27, P = .0341) and Hispanic races (OR 2.17, 95% CI 1.27-3.70, P = .0044) predicted higher rates of limb amputation than whites. Although our multivariable analyses showed that decreased use of sarcoma-directed surgery was only limited to age 85 + years, it also showed that older age predicted poorer cancer-specific mortality following sarcoma-directed surgery (P < .0001). CONCLUSIONS: In this US population-based study, the decreased use of sarcoma-directed surgery in the elderly was only limited to those older than 85 years. The association between older age and increased cancer-related mortality deserves future investigation to carefully examine potential effects of undertreatment. PMID- 20354802 TI - Humic acids as reducing agents: the involvement of quinoid moieties in arsenate reduction. AB - PURPOSE: Dissolved humic acids abiotically reduced inorganic arsenic to varying degrees, depending on solution pH, ionic strength, and type of humate used. The functionalities of dissolved organic matter responsible for these redox reactions remained in question, but quinoid moieties undoubtedly played an important role. It is not fully understood whether the quinoids are solely responsible for arsenate reduction, and what the kinetics of the relevant processes are. METHODS: Electron spin resonance (ESR) spectroscopy was used to monitor the radical content of the humates, both as bulk material and as size fractions. Information on the redox status of the humates was obtained from fluorescence excitation emission matrices and correlated with the observed spin count. Size data were obtained from fractionation and UV-Vis spectrometry. Arsenic speciation was carried out by ion chromatography. RESULTS: ESR spectroscopy showed a free radical content of 3.4 x 1,017-20 x 1,017 spins/g for bulk and fractionated aqueous humic acids. The number of electrons corresponding to these counts could not account for the entire charge transferred to arsenate during abiotic reduction. The rate constants of the reactions were found to be independent of the humic concentration. Leonardite humic acid separated on a XAD-8 resin yielded fractions that on the short time frame (0-5 h) had rate constants of 0.035 h(-1) for the hydrophobic fraction compared to 0.0052 h(-1) for the hydrophilic fraction. The rate constants for the hydrophobic and hydrophilic fractions over the longer time frame (100-200 h) were similar-7.3 x 10(-4) and 7.2 x 10(-4) h( 1), respectively. Fluorescence excitation-emission matrices of humates involved in arsenate reduction exhibited shifts typical of quinoid components undergoing redox transformations. These gradual shifts took place during the first 24 h of reduction process, after which the spectra no longer changed. The reduction of arsenate, however, continued after this period, indicating that species other than quinoids were involved. This was consistent with the fact that the rate constants for the later processes were smaller. CONCLUSIONS: The existence of different redox pools within the humate was confirmed, with the quinoid-centered redox entities showing the fastest kinetics. The results pertained to all size and polarity fractions. PMID- 20354803 TI - Simultaneous analysis of isoflavones and saponins in Pueraria flowers using HPLC coupled to an evaporative light scattering detector and isolation of a new isoflavone diglucoside. AB - The Pueraria flowers, Puerariae Flos [Puerariae Lobatae Flos (the flowers of P. lobata) and Puerariae Thomsonii Flos (the flowers of P. thomsonii)], have been used as crude drugs to counteract the overconsumption of alcohol in Japan and China. Both types of Puerariae Flos contain a large amount of isoflavones and saponins. Simultaneous analysis of the total saponin and isoflavone fraction within the flowers has proven difficult thus far; however, profile analysis of saponin and isoflavone levels was attempted in this study by using HPLC coupled to an evaporative light scattering detector (ELSD). A characteristic peak of kakkalide was common in the chromatograms of extracts originating from the flowers of P. lobata, though original habitats were different. Tiny peaks of saponins were also observed in chromatograms of all specimens derived from P. lobata. In the chromatograms of six out of eight extracts of Puerariae Thomsonii Flos originating from Guangdong, China, characteristic twin peaks corresponding to tectorigenin 7-O-xylosylglucoside and tectoridin were observed. The distinctive twin peaks were not found in the chromatograms of the extracts produced in Hunan and Sichuan. Although the amounts of total saponins and isoflavones obtained from Puerariae Lobatae Flos were almost the same, those of Puerariae Thomsonii Flos varied remarkably and were not related to habitat. A good yield of a new isoflavone glycoside was obtained from some specimens of Puerariae Thomsonii Flos; the structure was determined to be 6-hydroxygenistein 6,7-di-O-glucoside. PMID- 20354804 TI - New benzophenone and quercetin galloyl glycosides from Psidium guajava L. AB - New benzophenone and flavonol galloyl glycosides were isolated from an 80% MeOH extract of Psidium guajava L. (Myrtaceae) together with five known quercetin glycosides. The structures of the novel glycosides were elucidated to be 2,4,6 trihydroxybenzophenone 4-O-(6''-O-galloyl)-beta-D: -glucopyranoside (1, guavinoside A), 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6''-O-galloyl) beta-D: -glucopyranoside (2, guavinoside B), and quercetin 3-O-(5''-O-galloyl) alpha-L: -arabinofuranoside (3, guavinoside C) by NMR, MS, UV, and IR spectroscopies. Isolated phenolic glycosides showed significant inhibitory activities against histamine release from rat peritoneal mast cells, and nitric oxide production from a murine macrophage-like cell line, RAW 264.7. PMID- 20354805 TI - HIV neuropathogenesis: a tight rope walk of innate immunity. AB - During the course of HIV-1 disease, virus neuroinvasion occurs as an early event, within weeks following infection. Intriguingly, subsequent central nervous system (CNS) complications manifest only decades after the initial virus exposure. Although CNS is commonly regarded as an immune-privileged site, emerging evidence indicates that innate immunity elicited by the CNS glial cells is a critical determinant for the establishment of protective immunity. Sustained expression of these protective immune responses, however, can be a double-edged sword. As protective immune mediators, cytokines have the ability to function in networks and co-operate with other host/viral mediators to tip the balance from a protective to toxic state in the CNS. Herein, we present an overview of some of the essential elements of the cerebral innate immunity in HIV neuropathogenesis including the key immune cell types of the CNS with their respective soluble immune mediators: (1) cooperative interaction of IFN-gamma with the host/virus factor (platelet-derived host factor (PDGF)/viral Tat) in the induction of neurotoxic chemokine CXCL10 by macrophages, (2) response of astrocytes to viral infection, and (3) protective role of PDGF and MCP-1 in neuronal survival against HIV Tat toxicity. These components of the cerebral innate immunity do not act separately from each other but form a functional immunity network. The ultimate outcome of HIV infection in the CNS will thus be dependent on the regulation of the net balance of cell-specific protective versus detrimental responses. PMID- 20354807 TI - A meta-analysis of randomized controlled trials that compared laparoscopy assisted and open distal gastrectomy for early gastric cancer. AB - BACKGROUND: We conducted a meta-analysis to evaluate and compare the advantages of laparoscopy-assisted distal gastrectomy (LADG) over open distal gastrectomy (ODG) for treating early gastric cancer (EGC). METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and January 2010 by using the following search terms: laparoscopy-assisted gastrectomy, laparoscopic gastrectomy, and early gastric cancer. The following data were analyzed: operative time, estimated blood loss, number of harvested lymph nodes, time required for resumption of oral intake, duration of hospital stay, frequency of analgesic administration, complications, tumor recurrence, and mortality. RESULTS: We selected four papers reporting randomized control studies (RCTs) that compared LADG with ODG for EGC. Our meta-analysis included 267 patients with EGC; of these, 134 and 133 had undergone LADG and ODG, respectively. The volume of intraoperative blood loss, frequency of analgesic administration, and rate of complications were significantly lesser for LADG than for ODG. However, the time required for resumption of oral intake and duration of hospital stay did not significantly differ between LADG and ODG. The operative time for LADG was significantly longer than that for ODG; further, the number of harvested lymph nodes was significantly lesser in the LADG group than in the ODG group. CONCLUSION: LADG is advantageous over ODG because it results in lesser blood loss, is less painful, and is associated with a low risk of complications. Additional RCTs that compare LADG and ODG and investigate the long-term oncological outcomes of LADG are required to determine the advantages of LADG over ODG. PMID- 20354806 TI - Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence. AB - Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits. PMID- 20354809 TI - Infection rates in a large investigational trial of sacral nerve stimulation for fecal incontinence. AB - INTRODUCTION: Treatment options for patients with fecal incontinence (FI) are limited, and surgical treatments can be associated with high rates of infection and other complications. One treatment, sacral nerve stimulation (SNS), is approved for FI in Europe. A large multicenter trial was conducted in North America and Australia to assess the efficacy of SNS in patients with chronic fecal incontinence. The aim of this report was to analyze the infectious complication rates in that trial. METHODS: Adult patients with a history of chronic fecal incontinence were enrolled into this study. Those patients who fulfilled study inclusion/exclusion criteria and demonstrated greater than two FI episodes per week underwent a 2-week test phase of SNS. Patients who showed a > or = 50% reduction in incontinent episodes and/or days per week underwent chronic stimulator implantation. Adverse events were reported to the sponsor by investigators at each study site and then coded. All events coded as implant site infection were included in this analysis. RESULTS: One hundred twenty subjects (92% female, 60.5 +/- 12.5 years old) received a chronically implanted InterStim Therapy device (Medtronic, Minneapolis, MN, USA). Patients were followed for an average of 28 months (range 2.2-69.5). Thirteen of the 120 implanted subjects (10.8%) reported infection after the chronic system implant. One infection spontaneously resolved and five were successfully treated with antibiotics. Seven infections (5.8%) required surgical intervention, with infections in six patients requiring full permanent device explantation. The duration of the test stimulation implant procedure was similar between the infected group (74 min) and the non-infected group (74 min). The average duration of the chronic neurostimulator implant procedure was also similar between the infected (39 min) and non-infected group (37 min). Nine infections occurred within a month of chronic system implant and the remaining four infections occurred more than a year from implantation. While the majority (7/9) of the early infections was successfully treated with observation, antibiotics, or system replacement, all four of the late infections resulted in permanent system explantation. CONCLUSION: SNS for FI resulted in a relatively low infection rate. This finding is especially important because the only other Food and Drug Administration approved treatment for end-stage FI, the artificial bowel sphincter, reports a much higher rate. Combined with its published high therapeutic success rate, this treatment has a positive risk/benefit profile. PMID- 20354808 TI - Anastomotic sealing by extracellular matrices (ECM) improves healing of colonic anastomoses in the critical early phase. AB - BACKGROUND: Extracellular matrices have proven potential for in vivo tissue regeneration at gastrointestinal luminal organs. In this study, small intestinal submucosa (SIS) was tested as a sealant for colonic anastomoses in a rodent model. METHODS: In the rodent model, standard colonic anastomoses in the control group (CG; n = 30) and anastomoses sealed by omentum (n = 30) were compared to SIS-sealed anastomoses in the study group (SG; n = 30). After 4-, 30-, and 90-day macroscopic and microscopic healing, bursting pressure and anastomotic stricture rate were evaluated. RESULTS: The rate of anastomotic dehiscence was 1/10 after 4 days and 0/10 after 30 and 90 days in all groups. In the SG, the bursting pressure was significantly increased after 4 days compared to CG (148 +/- 9 vs. 108 +/- 8 mmHg; p > 0.05). Histologically, after 4 days of neovascularization, fibroblast ingrowth and collagen deposition were significantly increased in SG compared to CG. After 30 days, nonsignificant differences were noted in all three parameters. Adhesion rate and anastomotic stricture rate were not significantly affected by SIS sealing after 4, 30, and 90 days. CONCLUSION: Especially in the critical phase of anastomotic healing up to day 4, anastomotic healing was improved by SIS sealing. SIS sealing did not cause long-term complications. PMID- 20354810 TI - The first report on hybrid NOTES adjustable gastric banding in human. AB - BACKGROUND: Despite their current limitations, metabolic surgery and natural orifice transluminal endoscopic surgery (NOTES), set new horizons. In this article, the first three cases of adjustable gastric banding (AGB) through transvaginal access in obese women are described. METHODS: In the General and Vascular Surgery Department, Ceynowa Hospital, Poland, three cases of AGB through the transvaginal access in hybrid, laparoscopically assisted NOTES technique were performed. All patients were female with BMI range 35-37. A dual-channel endoscope and regular laparoscopic instruments were used. RESULTS: The mean operating time was 110 min. Indometacin was given intravenously PRN for postoperative pain. None of the patients required more than 3 g of indometacin and for longer than 24 h postoperatively. None required opioids either. There was one major complication of iatrogenic damage to the ureter, which required subsequent hospitalisation and laparoscopic repair. Hospitalisation time was 2 days. During 2 months follow up, the mean weight loss was 15 kg. There were no malpositions of the band. There was no early mortality in the study group. CONCLUSION: Feasibility of the proposed hybrid laparoscopically assisted NOTES adjustable gastric banding was proved. It is a technically demanding procedure, requiring appropriate endoscopic and laparoscopic skills. To avoid ureteric damage one should acquire safe colpotomy skills before commencing transvaginal NOTES operations. PMID- 20354812 TI - Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report. AB - Low-grade endometrial stromal sarcoma (ESS) is a rare neoplasm and is generally an indolent tumor with estrogen and progesterone receptors. Objective responses by hormonal treatment with progestin or aromatase inhibitor have been reported, however, long-term management of this disease could be difficult if it becomes refractory to one of these hormonal therapies. A 34-year-old woman was diagnosed with stage I low-grade ESS at the time of hysterectomy for presumed uterine fibroma. Five years later, she recurred with multiple tumors in the lower abdomen. After an optimal surgery, she was free from progression for 6 years with progestin treatment (medroxyprogesterone acetate: MPA, 200-600 mg daily). Thereafter, she recurred twice during the MPA treatment and received debulking surgery each time. MPA was discontinued at age of 53, because another recurrent tumor grew up to 13 cm in diameter. Aromatase inhibitor anastrozole was then given at a daily dose of 1 mg with partial response (the tumor size decreased to 7 cm in diameter) for a duration of 9 months. After complete resection of the recurrent tumor, she remains progression-free for 16 months. Anastrozole was effective to recurrent low-grade ESS even after being refractory to progestin therapy. Aromatase inhibitor treatment may be a useful option as a second-line hormonal treatment to low-grade ESS. PMID- 20354811 TI - Multifaceted role of heat shock protein 70 in neurons. AB - Heat shock protein 70 (Hsp70) plays important roles in neural protection from stress by assisting cellular protein folding. In this review we discuss the current understanding of inducible and constitutive Hsp70 in maintaining and protecting neuronal synaptic function under normal and stressed conditions. PMID- 20354813 TI - Expression of CDK5/p35 in resected patients with non-small cell lung cancer: relation to prognosis. AB - Overall outcome of those patients with non-small cell lung cancer (NSCLC) remains poor. Recently, several studies demonstrated that cyclin-dependent kinase-5 (CDK5) activity with its specific activator protein p35 was important for spontaneous metastasis in various types of carcinomas. Our objective was to explore the expression of CDK5 and its prognostic indicator in patients with NSCLC. Immunofluorescent staining was used to detect the expression of CDK5/p35 in the lung tissue of 95 patients with NSCLC and 20 patients with benign pulmonary disease. The correlation between the expression of CDK5/p35 and clinicopathologic features of patients with NSCLC was investigated. The 5-year overall survival of patients with tumors expressing different levels of CDK5/p35 was evaluated by the Kaplan-Meier method. Positive expressions of CDK5/p35 were detected in the tumor cells in 66 samples (69.5%) of the 95 patients with NSCLC. Although no remarkable correlation between CDK5/p35 expression and age at the time of surgery, gender, and histopathologic type, there were significant differences between CDK5/p35 expression and degree of differentiation, pathological stage and lymph node metastasis in patients with NSCLC. In addition, we demonstrated that median survival for patients with and without CDK5/p35 expression was 24 and 58 months, respectively, and 5-year overall survival rate 25.8 and 48.3%, respectively (P<0.05). Patients with lung cancer with a positive CDK5/p35 expression had a poorer prognosis than those with a negative CDK5/p35 expression. Based on our results, CDK5/p35 may represent a biomarker for prognosis in patients with NSCLC. PMID- 20354814 TI - Anti-cancer effects of 20(S)-protopanoxadiol on human acute lymphoblastic leukemia cell lines Reh and RS4;11. AB - Although the treatment outcome of acute lymphoblastic leukemia (ALL) has been improved in the past decades by combination chemotherapy, toxic side-effects of chemotherapeutics remain a major problem. Therefore, new alternative agents with low toxicity are urgently needed. Natural products provide a rich source of screening potential anti-cancer drugs. 20(S)-protopanoxadiol (PPD), a major gastrointestinal metabolic product of ginsenosides, exhibits promising anti cancer activity with low toxicity. However, the anti-cancer activity of PPD against ALL has not been evaluated. In this study, we examined the anti-cancer effect of PPD on ALL cell lines Reh and RS4;11. The growth of leukemia cells and normal cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The cell cycle, apoptosis and differentiation was determined by flow cytometry. The results showed that PPD inhibited the growth of Reh and RS4;11 cells, but had little toxicity to peripheral blood mononuclear cells (PBMC). PPD also blocked cell cycle progression from G0/G1 phase and induced cell differentiation. However, cell apoptosis was not affected. These data indicate that PPD exerts anti-cancer effects by stimulating differentiation and inhibiting growth and cell cycle progression of ALL cells. PMID- 20354815 TI - Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China. AB - Polymorphisms in DNA repair and apoptosis genes are suspected to alter the individual susceptibility to develop lung cancer. We investigated the relationship between polymorphisms in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu) and iASPP (A67T) and the risk of developing lung cancer. A case control study was conducted with 315 patients with lung cancer and 315 cancer free controls, matched on age and sex. Genotypes were detected using the ABI 7500 real-time PCR system. The T/T homozygote in ERCC1 (Asn118Asn) was correlated with a strong statistically significant increased risk of developing lung cancer (adjusted OR=2.44; 95% CI=1.13-5.28; P=0.023), especially lung adenocarcinoma (adjusted OR=3.18) and small cell lung cancer (adjusted OR=6.08). For iASPP (A67T), smokers with at least one T allele (A/T+T/T) were more likely to develop lung cancer (95% CI, 1.07-2.84, P=0.026). Subjects carrying the G allele in APE1 (Asn148Glu) had a decreased risk of lung cancer (P<0.05), which showing a protective effect. Our results suggest that polymorphism Asn118Asn in ERCC1, A67T in iASPP and Asn148Glu in APE1 may associated with early onset of lung cancer as well as some specific subtype of lung cancer. Detection of these biomarkers may be helpful for screening this high-risk population for primary preventing. PMID- 20354816 TI - Prognostic factors in elderly patients with non-small cell lung cancer: a two center experience. AB - Non-small cell lung cancer (NSCLC) is usually at advanced stage when it is diagnosed. There is no consensus about the standard treatment in elderly patients with advanced NSCLC. Generally, data regarding elderly patients with NSCLC are withdrawn from general NSCLC studies based on subgroup analyses and suggestions. We evaluated prognostic factors in elderly patients with advanced NSCLC. We reviewed retrospectively 338 patients from August 2005 to July 2009 in two centers in Turkey. Medical records of the patients>=65 years with advanced NSCLC were collected. Collected data included demographic informations, clinical assessments and information on treatment, toxicities and outcomes. Survival was estimated by using Kaplan-Meier method and prognostic factors were evaluated with log-rank and Cox regression tests. The median overall survival (OS) for the entire group was 15.4 months (95% CI: 12.7-18.0). In univariate analysis, weight loss, stage, combination therapy, second-line chemotherapy and tumor response (P<0.01) and performance status significantly affected OS (P<0.05). The median progression-free survival (PFS) was 10 months (95% CI: 8.4-11.6). In univariate analysis, there was only a significant association between tumor response and PFS (14.6 vs. 8.5 months; P<0.001). Multivariate analysis showed that only response to therapy was an important prognostic factor for OS (P<0.001). Survival of elderly patients with advanced NSCLC is significantly influenced by performance status, weight loss, stage, combination therapy, second-line chemotherapy and response to therapy. Not only age but also these factors may be kept in mind in the treatment planning of the elderly patients with NSCLC. These results may be of benefit in changing clinical practice in elderly patients with NSCLC who are often undertreated. PMID- 20354817 TI - The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast. AB - Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P>=0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma. PMID- 20354818 TI - The association between XPD Asp312Asn polymorphism and lung cancer risk: a meta analysis including 16,949 subjects. AB - To derive a more precise estimation of the relationship between the xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and lung cancer risk, a meta analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the XPD Asp312Asn polymorphism and lung cancer risk. The pooled ORs were performed with co-dominant model (Asp/Asn vs. Asp/Asp, Asn/Asn vs. Asp/Asp), dominant model (Asp/Asn + Asn/Asn vs. Asp/Asp), and recessive model (Asn/Asn vs. Asp/Asp+Asp/Asn), respectively. A total of 18 studies including 7,552 cases and 9,397 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with XPD Asn allele when all studies were pooled into the meta-analysis (Asn/Asn vs. Asp/Asp: OR=1.158, 95% CI=1.018 1.317; recessive model: OR=1.161, 95% CI=1.029-1.311). In the subgroup analysis by ethnicity, significantly increased risks were found for both Caucasians (Asn/Asn vs. Asp/Asp: OR=1.164, 95% CI=1.003-1.351; recessive model: OR=1.169, 95% CI=1.016-1.345) and Asians (Asn/Asn vs. Asp/Asp: OR=8.056, 95% CI=2.420 26.817; recessive model: OR=7.956, 95% CI=2.391-26.477). When stratified by study design, statistically significantly elevated risk was noted in hospital-based studies (Asn/Asn vs. Asp/Asp: OR=1.315, 95% CI=1.110-1.558; recessive model: OR=1.290, 95% CI=1.099-1.513). In conclusion, this meta-analysis suggests that the XPD Asn allele is a low-penetrant risk factor for developing lung cancer. PMID- 20354819 TI - Sunitinib in pretreated advanced non-small-cell lung carcinoma: a primary result from Asian population. AB - Sunitinib is an oral multitargeted tyrosine kinase inhibitor of VEGF receptors and PDGF receptors and is approved for the treatments of advanced renal cell carcinoma and gastrointestinal stromal tumors. However, only few studies were conducted to investigate the effectiveness of the use of sunitinib in NSCLC. This study evaluated the clinical activity and tolerability of sunitinib in previously treated advanced NSCLC in Asian population, which, to our knowledge, has not previously been studied. We conducted an open-label, non-randomized phase II trial for Asian patients with advanced NSCLC. Patients 18 years of age or older had histologically proven stage IIIB or IV NSCLC which had progressed during or after treatment with at least one platinum-based combination chemotherapy regimen were included in this study. In all, 22 patients were enrolled in this study. Two patients achieved a confirmed PR, giving an ORR of 9% (95% CI 0.1-20.9%). An additional 7 patients achieved SD for at least 8 weeks. The median PFS was 11.8 weeks (95% CI 8.2-15.3).The median OS was 23.4 weeks (95% CI 14.7-32.1). Treatments were generally well tolerated. Sunitinib, as a single agent, had a substantial activity for Asian patients who had pretreated advanced NSCLC. The toxicity profile was favorable. However, large population and high-quality prospective clinical trials are needed to be conducted. PMID- 20354820 TI - Neuroendocrine carcinoma of the esophagus: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA. AB - Neuroendocrine carcinoma of the esophagus including small-cell carcinoma and large-cell carcinoma is a very rare entity. The author herein reports a neuroendocrine carcinoma of the esophagus with an emphasis on KIT and PDGFRA. An 81-year-old man presented as dysphagia. An endoscopic examination revealed an ulcerated large tumor in the middle esophagus. A biopsy of the esophageal tumor identified an undifferentiated carcinoma consisting of malignant cells with hyperchromatic nuclei without differentiations. An immunohistochemical study revealed that the tumor cells were positive for cytokeratins, neuron-specific enolase, synaptophysin, p53 protein, KIT, and platelet-derived growth factor receptor-alpha (PDGFRA). The Ki-67 labeling was 100%. A pathologic diagnosis of neuroendocrine carcinoma with expression of KIT and PDGFRA was made. A genetic analysis using PCR direct sequencing method identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient underwent radiation and cisplatin-based chemotherapy. However, he developed systemic metastases and died of respiratory failure 8 months after the first manifestation. The present case is the first one of esophageal neuroendocrine carcinoma with an examination of protein expressions and gene mutations of KIT and PDGFRA. PMID- 20354821 TI - A retrospective study of the impact of age on patterns of care for elderly patients with metastatic breast cancer. AB - This study aims at evaluating the impact of age on patterns of care in elderly patients with metastatic breast cancer (MBC) and their outcome. We identified 177 patients aged >= 65 treated for MBC at the National Cancer Center Hospital in Japan from 1999 to 2007. We evaluated the impact of age on the selection of best supportive care (BSC) only, chemotherapy as first-line treatment, and chemotherapy after first-line endocrine therapy. Fisher's exact test and a multivariate logistic regression analysis with variables of age, performance status (PS), hormone receptor (HR) status, human epidermal growth factor-2 (HER2), and life-threatening disease (LTD) were used. The median age of patients was 72, and 60 patients (33.9%) were aged >= 75. HR-negative patients and those whose PS was >= 2, regardless of age, were more likely to choose BSC without chemotherapy. Multivariate analysis revealed age >= 75 (P = 0.018), positive-HR status (P < 0.001), and absence of LTD (P < 0.001) were significantly correlated to choose endocrine therapy rather than chemotherapy. In patients who had previous endocrine therapy, age (P = 0.008) and absence of HER2 (P = 0.018) were related not to choose chemotherapy. Not age but HR-negative status or PS >= 2 were related to the selection of BSC. In selecting endocrine therapy rather than chemotherapy, age (>= 75), HR-positive, and absence of LTD were significant factors. In patients failed to endocrine therapy, age and HER2 status were correlated to decision-making to choose chemotherapy. PMID- 20354823 TI - Evaluation of efficacy and safety of generic levofolinate in patients who received colorectal cancer chemotherapy. AB - The efficacy and safety of generic and brand name levofolinate injectable drugs were evaluated in 42 chemotherapy-naive patients with colorectal cancer who received the combination chemotherapy of levofolinate, 5-fluorouracil, and oxaliplatin with or without bevacizumab. The tumor response rate was similar between generic drug group and brand drug group, in which the efficacy rate (complete response plus partial response) was 50% for generic drug group and 42% for brand name drug (odds ratio: 1.400, 95% confidence intervals: 0.409-4.788, P = 0.756). The rates of the decrease in plasma tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were not different between the two groups. The incidence of adverse drug reactions was not significantly different between the two groups, although the incidence rates of adverse events associated predominantly with 5-fluorouracil such as hand-and-foot syndrome, diarrhea, and oral mucositis were rather higher, though not significantly, in generic drug group than in brand drug group (16 vs. 4% for hand-and-foot syndrome; 33 vs. 25% for diarrhea; 33 vs. 25% for oral mucositis). These findings suggest that both the effectiveness and safety profiles of the generic name levofolinate are comparable to those of the brand name drug, when used in combination with 5-fluorouracil and oxaliplatin in patients with colorectal cancer. PMID- 20354822 TI - Health-related quality of life assessment in prospective trials of systemic cytotoxic chemotherapy for metastatic castration-resistant prostate cancer: which instrument we need? AB - Knowledge about psychological health of men with prostate cancer is still limited. HRQoL assessment adds value in symptom management by allowing a broader understanding of the impact of symptom management beyond the targeted symptom, on functioning, and on overall QoL. In this paper, the results of the commonly used HRQoL questionnaires in phase III randomized clinical trials of chemotherapy in metastatic castration-resistant prostate cancer has been discussed. An overview about symptom burden, treatments and HRQoL domains, a description of available HRQoL instruments used for patients with metastatic castration-resistant prostate cancer were reported. Finally, the characteristics of most commonly used HRQoL instruments were identified and compared. To provide better empirical justification for the selection of HRQoL instruments, head-to-head comparisons of them within the same studies are needed. Estimating a minimal important difference could be significant when interpreting trial results. The impact of HRQoL scores in clinical practice remains unclear; poor communication of clinical significance of the results and limited training of clinicians are the most important barriers to a widespread use of HRQoL questionnaires. PMID- 20354824 TI - Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features. AB - Acute myeloid leukemia (AML) with normal karyotype represents a clinically and molecularly heterogeneous disease. Molecular markers with prognostic significance have been examined to improve risk profile characterization of this group. Activating mutations on FLT3 receptor are one of the most common genetic alterations reported. However, the prevalence and prognostic significance of FLT3 genetic alterations in AML patients with cytogenetically normal karyotype is still controversial. In this study, FLT3/ITD and FLT3/D835 mutations were analyzed in 133 patients with de novo AML with normal cytogenetics by genomic PCR assay. Of 133 patients with AML with normal cytogenetics, FLT3 internal tandem duplication (ITD) and FLT3/D835 mutations were detected in 27 (20%) and 4 (3%) samples, respectively. Although statistically insignificant, the frequency of FLT3/ITD was higher in >15 year age group when compared to <15 year group (23 vs. 13%, P = 0.2). The white blood count was found to be significantly higher in patients with FLT3/ITD mutation when compared to those without the mutation (40 * 109/L vs. 20 * 109/L, P = < 0.002) or those with FLT3/D835 mutations (30 * 109/l). Aberrant expression of CD7 was observed more frequently in patients with FLT3/ITD mutation (P < 0.002). There was no significant difference in the response rate to chemotherapy in patients with or without FLT3/ITD mutation (67 and 64%, respectively). FLT3/ITD mutation was found to be associated with the age, leukocytosis and aberrant expression of CD7, although no influence of FLT3/ITD mutation was seen on the clinical outcome of AML patients with normal cytogenetics. PMID- 20354825 TI - Int7G24A variant of transforming growth factor-beta receptor 1 is associated with osteosarcoma susceptibility in a Chinese population. AB - The TGF-beta signaling pathway is important in the development and invasion of cancers. Int7G24A is an intronic variant of TGF-beta receptor type 1 and has been shown to be associated with the occurrence of some kinds of cancers. Nevertheless, the association of this polymorphism with osteosarcoma is unknown. In this study, we evaluated Int7G24A variant frequencies in osteosarcoma cases. The case-control study involved 168 osteosarcoma patients and 168 age- and gender matched controls. The blood samples were obtained, and Int7G24A variant was determined by PCR amplification and DNA sequencing. The odds ratio (OR) and 95% confidence interval (95% CI) for the Int7G24A polymorphism were calculated using unconditional logistic regression adjusted for age and gender. Three analysis models, which are the dominant model, additive model and recessive model, were used to analyze the contribution of Int7G24A variant to osteosarcoma susceptibility. Heterozygotic and homozygotic Int7G24A variants were 33.93 and 6.55% in total 168 cases, while they were 28.57 and 2.98%, respectively, in total 168 controls. The ORs for homozygosity and heterozygosity of Int7G24A allele were 1.56 [95% CI, 0.98-1.83] and 2.89 [95% CI, 1.46-4.92] in additive model. The ORs of Int7G24A genotypes in dominant model and in recessive model were 1.75 [95% CI, 1.21-2.68] and 2.21 [95% CI, 1.34-4.72], respectively. There were significant increases in Int7G24A variants in osteosarcoma cases when compared to control in every three models. Further analysis showed that Int7G24A genotypes were not associated with gender and osteosarcoma location of the cases. However, Int7G24A was significantly increased in the cases less than 20 years old. Moreover, Int7G24A was significantly associated with increased distant metastasis of osteosarcoma. It is concluded that Int7G24A is a polymorphism of TGFBR1 that is associated with the susceptibility and distant metastasis of osteosarcoma. PMID- 20354826 TI - Reduced selenium-binding protein 1 is associated with poor survival rate in gastric carcinoma. AB - Human selenium-binding protein 1 (SBP1) is known to play a key role in the development and progression of many cancers. The role of SBP1 expression in gastric carcinoma (GC) is far from being fully established. The aim of the present study was to evaluate the expression of SBP1 in GC and correlate the findings with several clinicopathological features and prognosis. Tissue samples from 65 patients treated by gastric resection for GC with clinical stage II and III were used. Each sample was matched with the corresponding nonneoplastic epithelia tissues removed during the same surgery. Reverse transcriptase polymerase chain reaction, immunostaining and Western blot analyses were used to detect the expression of SBP1 at the mRNA and protein levels, respectively. The associations between SBP1 expressions and clinicopathological features were analyzed. Expressions of SBP1 at both mRNA and protein levels were significantly lower in GC than those in the corresponding nonneoplastic epithelia tissues (P = 0.000). SBP1-negative expression had a significant relationship with high clinical stage (P = 0.038). Prognosis of SBP1-negative patients was significantly poorer than that of SBP1-positive patients (P = 0.001), and multivariate analysis further confirmed that SBP1 was an independent prognostic factor (P = 0.004). Thus, down-regulation of SBP1 may play a key role in the tumorigenic process of human GC. The correlation of SBP1 reduction in GC with clinical stage and survival proposes a prognostic role in GC. PMID- 20354828 TI - Combination of simvastatin and imatinib sensitizes the CD34+ cells in K562 to cell death. AB - Chronic myeloid leukemia (CML) is a hematological malignancy, 95% of which is due to translocation between chromosomes 9 and 22 and the resulting bcr-abl fusion protein. Imatinib specifically binds to the bcr-abl and inhibits cancer cells. However, a subpopulation of the CML cells named leukemia stem cells are resistant to the imatinib therapy, leading to the relapse. In this study, we identified a subpopulation of CD34+ cells in K562 were much more resistant to imatinib than the bulk cells. Simvastatin single also had little pro-apoptotic effect on the CD34+ cells. In contrast, combination of simvastatin and imatinib induced a significant cell death in the subpopulation, which is dependent on the induced ROS by simvastatin as the effect was blocked by ROS scavenger N-acetyl-L: cysteine (NAC). Our data here point out that combination of simvastatin and imatinib could be a therapeutic option for the resistant CML. PMID- 20354827 TI - Clinical significance of the immunostimulatory MHC class I chain-related molecule A and NKG2D receptor on NK cells in pancreatic cancer. AB - The aim of this paper was to determine the clinical significance of the MHC class I chain-related molecule A(MICA) and NKG2D receptor on NK cells in pancreatic cancer. We compared MICA expression in malignant (n = 103), inflammatory (n = 28), and normal (n = 17) pancreatic tissues using immunohistochemistry and assessed serum levels of soluble MICA (sMICA) and NKG2D expression on NK cells in patients with pancreatic cancer (n = 103), in patients with chronic pancreatitis (n = 28), and in healthy volunteers (n = 43). Expression of MICA was detected in 89.3% of pancreatic cancer tissues, whereas fewer were expressed in inflammatory and normal pancreatic tissues. The levels of sMICA were frequently elevated in patients with advanced pancreatic cancer. The elevation of sMICA was associated with down-regulated NKG2D expression and impaired activity of NK cells. The successful tumor resection significantly decreased serum levels of sMICA and increased the NKG2D expression; there was an inverse correlation between change in sMICA levels and that in NKG2D expression. MICA expression, preoperative sMICA levels and NKG2D intensity were found to be independent prognostic factors in resected pancreatic cancer. This study supports the clinical significance of release of MICA for the malignant progression of pancreatic cancer. The successful tumor resection for pancreatic cancer may have a beneficial effect on NKG2D-mediated antitumor immunity. Our results also suggest sMICA and NKG2D expression on NK cells may be useful to identify risk patients at time point of diagnosis. PMID- 20354829 TI - Primary malignant fibrous histiocytoma of spleen with spontaneous rupture: a case report and literature review. AB - Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma that mainly occurs in the lower and upper extremities, trunk and retroperitoneum. However, primary MFH of the spleen is especially rare. Only 11 cases of splenic MFH have been reported in the English literature. In this report, we describe a 35-year-old man who was found to have a large accumulation of free fluid in the abdominal cavity and a tumor mass 6 cm in diameter with rupture within the spleen by the abdominal ultrasonography. A splenectomy was performed and the histological diagnosis was malignant fibrous histiocytoma. The patient died 7 months after the operation as a result of generalized metastasis. Compared with the 11 previously documented patients of splenic MFH, our patient is the youngest and the first case with spontaneous rupture, which makes our case exceedingly rare. A literature review of primary MFH of spleen is also provided. PMID- 20354830 TI - 1H, 13C, and 15N resonance assignment of the TIR domain of human MyD88. AB - Myeloid differentiating factor 88 (MyD88) is one of a critical adaptor molecule in the Toll-like receptor (TLR) signaling pathway. The TIR domain of MyD88 serves as a protein-protein interaction module and interacts with other TIR-containing proteins such as Mal (MyD88 adaptor-like) and Toll-like receptor 4 to form signal initiation complexes. Here we report the (15)N, (13)C, and (1)H chemical shift assignments of the TIR domain of MyD88. The resonance assignments obtained in this work will contribute to the study of heteromeric TIR-TIR interactions between MyD88 and TIR-containing receptors or adaptors. PMID- 20354831 TI - Refractory lung metastasis from breast cancer treated with multidisciplinary therapy including an immunological approach. AB - A suggestive case of metastatic disease from breast cancer is reported. The HER-2 positive tumor was refractory to several agents, including anti-HER-2 therapy, trastuzumab, and lapatinib. After re-induction of trastuzumab in combination with activated natural killer (NK) cell injection therapy, tumor markers decreased, and finally a synergistic effect of taxane and capecitabine led to treatment response. This case suggests that multidisciplinary therapy including an immunological approach might be a breakthrough in the treatment of refractory disease. PMID- 20354832 TI - Secondhand smoke policy and the risk of depression. AB - BACKGROUND: Banning smoking in work and public settings leads to immediate reductions in disease burden. However, no previous studies have looked specifically at the impact smoking bans may have on depression. METHODS: The 2006 Behavioral Risk Factor Surveillance System (BRFSS) uses a cross-sectional design representative of the non-institutionalized civilian US population. Never smoker survey participants > or =18 years of age were selected from the BRFSS (n = 41,904) with their self-report of depressive symptoms in the last 2 weeks, as assessed by the Patient Health Questionnaire. Models with adjustment for survey design, sociodemographics, alcohol consumption, and work and home smoking policies were considered. RESULTS: Following covariate adjustment, the risk of major depression was significantly higher for those living where smoking was allowed anywhere in the home versus those living in homes with complete smoking bans and in those who indicated that smoking was permitted in their work areas versus those reporting complete workplace smoking bans. CONCLUSIONS: Findings from the present analysis support policies that ban smoking in all workplace settings. Interventions designed to eliminate smoking in the home are also needed. PMID- 20354833 TI - Report on the Women in Physiology Symposium in IUPS 2009. AB - A symposium entitled "Women in Physiology" was held on 30 July 2009 during IUPS in Kyoto. Seven female researchers from five countries presented their views. This article includes the summary of each speaker's talk. Figures are not included here because they have been uploaded to the web site of Women Physiologists of Japan (WPJ) ( http://square.umin.ac.jp/wpj/ ) with the permission of each speaker. Please visit this internet site, download the files freely, and use them for presentations. PMID- 20354834 TI - Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men. AB - The aim of this study was to follow up whether the modification of pro antioxidant status by 8-day oral application of N-acetylcysteine (NAC) in healthy men affects the haematological response, whether there is a direct relationship between antioxidant defences and erythropoietin (EPO) secretion and whether NAC intake enhances exercise performance. Fifteen healthy men were randomly assigned to one of two groups: control or NAC (1,200 mg d(-1) for 8 days prior to and 600 mg on the day of exercise trial). To measure the ergogenic effectiveness of NAC, subjects performed incremental cycle exercise until exhaustion. NAC administration significantly influenced the resting and post-exercise level of glutathione (+31%) as well as the resting activity of glutathione enzymes (glutathione reductase, -22%; glutathione peroxidase, -18%). The oxidative damage markers, i.e., protein carbonylation and lipid peroxidation products (thiobarbituric acid reactive substance) were reduced by NAC by more than 30%. NAC noticeably affected the plasma level of EPO (+26%), haemoglobin (+9%), haematocrit (+9%) and erythrocytes (-6%) at rest and after exercise. The mean corpuscular volume and the mean corpuscular haemoglobin increased by more than 12%. Plasma total thiols increased by 17% and directly correlated with EPO level (r = 0.528, P < 0.05). NAC treatment, contrary to expectations, did not significantly affect exercise performance. Our study has shown that 8-day NAC intake at a daily dose of 1,200 mg favours a pro-antioxidant status and affects haematological indices but does not enhance exercise performance. PMID- 20354835 TI - A survey of head and neck cancer curriculum in United States speech language pathology masters programs. AB - We surveyed speech language pathology (SLP) programs for head and neck cancer (HNC) training. Program directors of 242 American Speech-Language-Hearing Association accredited masters programs for SLP were contacted regarding curricular HNC material. Directors (n = 120) responded online: six included a required course in HNC, and all but two programs with no required HNC course included HNC topics in other required courses. Thirty-two programs were affiliated with a medical center and/or a teaching hospital. Programs that offered either a required course in HNC or elective courses on HNC were more likely to be affiliated with a medical center and/or a teaching hospital than programs that did not offer a required course in HNC (P = 0.043) or elective courses on HNC (P = 0.007), respectively. Few programs offer a required HNC course but most programs integrate HNC content into the required coursework. Potential strategies to incorporate HNC exposure into formal SLP programs are identified. PMID- 20354836 TI - Malocclusion, mastication and the gastrointestinal system: a review. AB - The relationship between malocclusion and the gastrointestinal system has only been examined occasionally, while several pertinent studies have addressed the chewing function as a functional link between oral structures and the gastrointestinal tract. Following an overview of the physiological masticatory process, the available evidence regarding associations among dental status, chewing function and gastrointestinal disorders are summarized. Finally, a review of the relationships between orthodontic deformities and mastication is presented. PMID- 20354837 TI - Young patients' attitudes toward removable appliance wear times, wear-time instructions and electronic wear-time measurements--results of a questionnaire study. AB - OBJECTIVE: To determine the attitude of young patients to removable appliance wear times, wear-time instructions and electronic wear-time measurement. PATIENTS AND METHODS: 140 patients (mean age 11.97 years) undergoing orthodontic treatment with removable appliances expressed their wishes about wear times and wear-time instructions in a questionnaire. The questionnaires were analyzed by means of descriptive statistical analysis. RESULTS: Analysis of this questionnaire investigation according to gender revealed that the majority of the respondents preferred wearing their appliances overnight only, and that they did not want their practitioners determining the length of the appliance wear. We observed gender-specific differences in the acceptance of wear times as determined by the dental practitioner, which were accepted by 58% of the girls but only 28% of the boys. Willingness to wear a removable appliance increased markedly when the orthodontic objectives included offering patients the prospect of an improvement in their appearance from wearing a removable appliance. A recently-developed removable appliance with an integrated microsensor on the market that provides an objective measure of appliance wear times would only be worn without reservations by about 21% of boys and 32% of girls. 41-45% of the respondents only agreed to treatment using this kind of microsensor provided the treatment period would be thereby shortened. CONCLUSIONS: The extent to which the clinician can respond to the wishes and requirements of young patients in terms of removable appliance wear is crucial to the compliance necessary for success. Acceptance of a removable appliance with an integrated electronic wear-time recorder can be enhanced if the practitioner explains to the patient in a simple, straightforward manner the therapeutic advantage of this new generation of appliances. Society's growing openness towards electronic devices does not yet appear to be reflected in the desire of young patients for braces with an integrated microsensor. PMID- 20354838 TI - Effect of smoking on the failure rates of orthodontic miniscrews. AB - OBJECTIVE: The aim of this study was to investigate the effect of cigarette smoking on the failure rates of orthodontic miniscrews. PATIENTS AND METHODS: Our cohort consisted of 88 patients with a total of 110 orthodontic miniscrews. Based on their smoking habits, the patients were divided into three groups: the light smokers (< or = 10 cigarettes/day), heavy smokers (> 10 cigarettes/ day), and non smokers. The light-smoker group consisted of 14 patients with 18 orthodontic miniscrews, and there were 15 patients with 19 miniscrews among the heavy smokers. The nonsmoker group contained 59 patients with a total of 73 miniscrews. RESULTS: The overall failure rate was 18.2% (n = 20). Heavy smokers revealed a significantly higher failure rate than light smokers (p = 0.005) or non-smokers (p < 0.001). No significant differences were observed between non-smokers and light smokers. Miniscrews in the heavy smoker group exhibited a significantly higher failure rate during the first 4 months after insertion than did the miniscrews in the light smokers (p = 0.008) or non-smokers (p < 0.001). CONCLUSION: Our results suggest that heavy smoking has a detrimental effect on the success rates of orthodontic miniscrews. PMID- 20354839 TI - B-mode and M-mode Ultrasonography of Tongue Movements during Swallowing. AB - OBJECTIVE: This study investigated the possibility of using B-mode and M-mode ultrasonography to differentiate between the visceral and somatic swallowing patterns. SUBJECTS AND METHODS: Tongue movements during empty swallowing by 11 volunteers with a visceral swallowing pattern were traced in B-mode and M-mode ultrasound imaging before and after successful myofunctional therapy. Thirteen subjects with a somatic swallowing pattern served as the control group. We examined and compared the B-mode sequences and M-mode images of at least six of each study subject's swallowing processes for reproducible characteristics and parameters. RESULTS: We observed wide intraindividual variability, making interindividual comparison difficult or meaningless. We identified no qualitative characteristic features in B-mode imaging that could be designated as solely visceral or physiological swallowing movements. There was no obvious intraindividual reproducibility in the M-mode sonogram of the swallowing act. Given the experimental set-up we used (without a submandibular cushioning pad), it was not possible to differentiate individual swallowing phases, that is, the initial, transporting, and returning phases, on the M-mode images based on characteristic trace points, as described in the literature. We determined the amplitude and velocity of vertical tongue movement as well as total swallowing duration on the M-mode images. These parameters revealed wide intra- and interindividual variability. CONCLUSIONS: No qualitative differences could be established in B-mode imaging with the ultrasound method selected for this study. The parameters that could be measured on the M-mode images are not suitable for differentiating between visceral and somatic swallowing. PMID- 20354840 TI - 3D soft tissue changes in facial morphology in patients with cleft lip and palate and class III mal occlusion under therapy with rapid maxillary expansion and delaire facemask. AB - AIM: Rapid Maxillary Expansion (RME) and Delaire facemask are a well-established treatment method for patients with cleft lip and palate and Class III malocclusion. Several roentgenocephalometric studies on skeletal effects of this therapy are known. However, there are no systematic studies on soft tissue changes. The aim of this study was to analyze three-dimensionally the soft tissue changes in facial morphology of children with cleft lip and palate and Class III malocclusion under therapy with RME and Delaire facemask. PATIENTS AND METHOD: A prospective longitudinal clinical trial was undertaken. 29 children between 4.1 and 6.4 years were divided into four groups: eight patients with unilateral cleft lip and palate (group 1), six patients with isolated cleft palate (group 2), eight patients with Class III malocclusion (group 3). The mean treatment period with RME and Delaire mask was 8.2 months. Seven untreated children with no need of orthodontic treatment were chosen as the control (group 4). Two 3D images, one at the beginning and one at the end of the study, were generated with the DSP 400((c)) imaging system. Both images were superimposed ten times and measured ten times. RESULTS: We detected significant forward rotation and forward displacement of the soft tissue in the lower midface with the dentoalveolar areas in all patient groups. No significant asymmetric forward displacement of the soft tissue in the maxilla could be verified in the lower or upper midface, not even in the unilateral cleft lip and palate patients. Among the groups, the Class III malocclusion patients showed greater maxillary soft tissue changes. CONCLUSION: The RME and the Delaire facemask demonstrated the greatest effectiveness in the lower midface soft tissue in terms of forward displacement and forward rotation in the cleft lip and palate patients, particularly in the Class III patients. The 3D data allowed us to discriminatively interpret the effects of the orthopedic mask on the entire maxillary complex and maxillary alveolar process. In the unilateral cleft lip and palate patients, there was descriptively both symmetric and asymmetric advancement of the midface soft tissue. PMID- 20354841 TI - Modified camouflage therapy in an adult class I patient with TMJ complaints. A case report. AB - The present case report documents the hitherto unusual application of camouflage orthodontics in one of our patients. Our female patient had previously been treated orthodontically alio loco and had also undergone bimaxillary orthognathic surgery. She presented with TMJ complaints, with associated pains. Despite a dental Class I and centrally seated condyles, her discs had prolapsed anteriorly without reduction and she had developed a massive degenerative-inflammatory TMJ disease. Skeletally, she was a Class II case despite previous orthognathic surgery. In addition, there was also an initial suspicion of rheumatic involvement that could not be confirmed. We distalized the entire lower dental arch without bicuspid extraction. Then we advanced the mandible with the Mandibular Anterior Repositioning Appliance (MARA).We discuss exactly how the modified camouflage therapy was structured and how the individual treatment steps took place. PMID- 20354842 TI - TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. AB - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and agonistic anti-DR4/TRAIL-R1 and anti-DR5/TRAIL-R2 antibodies are currently under clinical investigation for treatment of different malignancies. TRAIL activates DR4 and DR5 and thereby triggers apoptotic and non-apoptotic signaling pathways, but possible different roles of DR4 or DR5 in these responses has poorly been addressed so far. In the present work, we analyzed cell viability, DISC formation as well as IL-8 and NF-kappaB activation side by side in responses to TRAIL and agonistic antibodies against DR4 (mapatumumab) and against DR5 (lexatumumab) in pancreatic ductal adenocarcinoma cells. We found that all three reagents are able to activate cell death and pro-inflammatory signaling. Death-inducing signaling complex (DISC) analysis revealed that mapatumumab and lexatumumab induce formation of homocomplexes of either DR4 or DR5, whereas TRAIL additionally stimulated the formation of heterocomplexes of both receptors. Notably, blocking of receptors using DR4- and DR5-specific Fab fragments indicated that TRAIL exerted its function predominantly via DR4. Interestingly, inhibition of PKC by Goe6983 enabled DR5 to trigger apoptotic signaling in response to TRAIL and also strongly enhanced lexatumumab-mediated cell death. Our results suggest the existence of mechanisms that silence DR5 for TRAIL- but not for agonistic antibody treatment. PMID- 20354843 TI - Isolation of a novel bacterium, Blautia glucerasei sp. nov., hydrolyzing plant glucosylceramide to ceramide. AB - A bacterial strain that is capable of hydrolyzing plant glucosylceramide (GluCer) was newly isolated from dog feces. The novel strain, designated as strain HFTH 1(T), hydrolyzed plant GluCer with a variety of chemical structures, but did not hydrolyze glucosylsphingosine, lactosylceramide, or monosialoganglioside GM(3), indicating that strain HFTH-1(T) produces GluCer-specific glucosylceramidase. Strain HFTH-1(T) was Gram-positive, anaerobic, oval-spore-forming, rod-shaped, lecithinase-negative, and lipase-negative. It fermented a wide variety of carbohydrates and produced mainly acetate, formate, and lactate from glucose. The G + C content of its DNA was 40.7 mol%. The phylogenetic analysis of 16S rRNA sequence revealed that strain HFTH-1(T) is placed in the clostridial rRNA cluster XIVa, with Ruminococcus obeum as the nearest relative. Pairwise comparison revealed approximately 5.0% sequence divergence between strain HFTH-1(T) and the type strain of R. obeum. On the basis of its phenotypic characteristics and phylogenetic divergence, it is proposed that the hitherto unknown rod-shaped bacterial strain HFTH-1(T) (= DSM 22028(T) = NBRC 104932(T)) should be placed in the genus Blautia as a novel species, Blautia glucerasei sp. nov, the only currently known isolate of the species. PMID- 20354844 TI - Aspergillus nidulans contains six possible fatty acyl-CoA synthetases with FaaB being the major synthetase for fatty acid degradation. AB - Aspergillus nidulans can use a variety of fatty acids as sole carbon and energy sources via its peroxisomal and mitochondrial beta-oxidation pathways. Prior to channelling the fatty acids into beta-oxidation, they need to be activated to their acyl-CoA derivates. Analysis of the genome sequence identified a number of possible fatty acyl-CoA synthetases (FatA, FatB, FatC, FatD, FaaA and FaaB). FaaB was found to be the major long-chain synthetase for fatty acid degradation. FaaB was shown to localise to the peroxisomes, and the corresponding gene was induced in the presence of short and long chain fatty acids. Deletion of the faaB gene leads to a reduced/abolished growth on a variety of fatty acids. However, at least one additional fatty acyl-CoA synthetase with a preference for short chain fatty acids and a potential mitochondrial candidate (AN4659.3) has been identified via genome analysis. PMID- 20354845 TI - Fluorescent cell-based sensing approaches for toxicity testing. AB - Fluorimetric cell-based sensing methods have attracted increasing interest in toxicity testing of pharmaceuticals, pathogens, environmental pollutants, and other chemicals. The objective of this review is to summarise the variety of approaches reported up to now and to present recent developments in this area. The different approaches are described in relation to their underlying mechanism and, especially, to the role of the fluorophore involved. The methods discussed include the use of fluorescent or fluorogenic indicators, fluorescence-based testing for membrane integrity, approaches based on fluorescence labelling, inducible fluorescent protein expression, and analysis of cellular autofluorescence. Several of these approaches have been shown to be advantageous in comparison with non-fluorescence methods and have potential in high-throughput screening, for example in drug discovery and safety pharmacology. PMID- 20354846 TI - A novel technology for the detection, enrichment, and separation of trace amounts of target DNA based on amino-modified fluorescent magnetic composite nanoparticles. AB - A novel, highly sensitive technology for the detection, enrichment, and separation of trace amounts of target DNA was developed on the basis of amino modified fluorescent magnetic composite nanoparticles (AFMN). In this study, the positively charged amino-modified composite nanoparticles conjugate with the negatively charged capture DNA through electrostatic binding. The optimal combination of AFMN and capture DNA was measured by dynamic light scattering (DLS) and UV-vis absorption spectroscopy. The highly sensitive detection of trace amounts of target DNA was achieved through enrichment by means of AFMN. The detection limit for target DNA is 0.4 pM, which could be further improved by using a more powerful magnet. Because of their different melting temperatures, single-base mismatched target DNA could be separated from perfectly complementary target DNA. In addition, the photoluminescence (PL) signals of perfectly complementary target DNA and single-base mismatched DNA as well as the hybridization kinetics of different concentrations of target DNA at different reaction times have also been studied. Most importantly, the detection, enrichment, and separation ability of AFMN was further verified with milk. Simple and satisfactory results were obtained, which show the great potential in the fields of mutation identification and clinical diagnosis. PMID- 20354849 TI - Localized tenosynovial giant cell tumor in both knee joints. AB - Tenosynovial giant cell tumor, previously called pigmented villonodular synovitis (PVNS), is a rare benign neoplastic process that may involve the synovium of the joint. The disorder is usually monoarticular and only a few cases have been reported on polyarticular involvement. Herein, we present a case of localized intra-articular tenosynovial giant cell tumor in a 29-year-old man involving both knee joints with a description of the MR imaging and histological findings. PMID- 20354848 TI - Aortic arch malformations. AB - Although anomalies of the aortic arch and its branches are relatively uncommon malformations, they are often associated with congenital heart disease. Isolated lesions may be clinically significant when the airways are compromised by a vascular ring. In this article, the development and imaging appearance of the aortic arch system and its various malformations are reviewed. PMID- 20354851 TI - First demonstration of 3-D lymphatic mapping in breast cancer using freehand SPECT. AB - PURPOSE: Freehand SPECT is a 3-D tomographic imaging modality based on data acquisition with a hand-held detector that is moved freely, in contrast to conventional, fixed gamma camera systems. In this pilot study, the feasibility of freehand SPECT for 3-D lymphatic mapping in breast cancer was evaluated. METHODS: A total of 85 patients (age: 29-88 years) with an initial diagnosis of invasive breast cancer and no clinical evidence of nodal involvement prospectively underwent sentinel lymph node (SLN) biopsy. Preoperative lymphatic mapping (35-87 MBq (99m)Tc-Nanocoll) included tomographic imaging with a SPECT/CT device (Siemens Symbia T6) serving as reference. Initially, the freehand SPECT approach was assessed in a pilot study consisting of 50 patients. The quality of each freehand SPECT acquisition was assessed and ranked as good, intermediate or poor. In another series comprising a further 35 patients (validation study), a guidance system for the acquisition was implemented based on the results of the pilot study, ensuring acquisitions with good quality. For 3-D tomographic image reconstruction, ad hoc models and iterative reconstruction algorithms were used in all 85 patients. To allow for adequate comparison, SPECT/CT data and freehand SPECT data were registered within the same coordinate system. RESULTS: In the pilot study, freehand SPECT enabled mapping of 24 of 83 SLNs in 20 of 44 patients (3 dropouts, 3 patients without SLN either in SPECT/CT or in freehand SPECT). Using SPECT/CT as reference, the accuracy of freehand SPECT was 77.8% (7/9 nodes) in scans with good quality, while for intermediate and poor quality scans, the accuracy was reduced to 34.3 and 12.8%, respectively. In the validation study, quality feedback improved the results significantly and freehand SPECT enabled the mapping of at least one SLN in 87.5% of the patients (28/32 - 3 dropouts). Compared to the reference method, freehand SPECT showed a sensitivity of 83.3% (35/42 nodes). False-negative findings were related to insufficient scanning time, insufficient coverage of the axillary region, close proximity of the SLN to the injection site and low tracer uptake in the SLNs. CONCLUSION: In this preliminary study, we could demonstrate that 3-D localization of SLNs is feasible using freehand SPECT technology. Prerequisites for acquisition of a good scan quality, most likely allowing precise SLN mapping, have been defined. This approach has high potential to allow image-guided biopsy and further standardization of SLN dissection, thus bringing 3-D nuclear imaging into the operating room. PMID- 20354847 TI - Molecular evolution of regulatory genes in spruces from different species and continents: heterogeneous patterns of linkage disequilibrium and selection but correlated recent demographic changes. AB - Genes involved in transcription regulation may represent valuable targets in association genetics studies because of their key roles in plant development and potential selection at the molecular level. Selection and demographic signatures at the sequence level were investigated for five regulatory genes belonging to the knox-I family (KN1, KN2, KN3, KN4) and the HD-Zip III family (HB-3) in three Picea species affected by post-glacial recolonization in North America and Europe. To disentangle neutral and selective forces and estimate linkage disequilibrium (LD) on a gene basis, complete or nearly complete gene sequences were analysed. Nucleotide variation within species, haplotype structure, LD, and neutrality tests, in addition to coalescent simulations based on Tajima's D and Fay and Wu's H, were estimated. Nucleotide diversity was generally low in all species (average pi = 0.002-0.003) and much heterogeneity was seen in LD and selection signatures among genes and species. Most of the genes harboured an excess of both rare and frequent alleles in the three species. Simulations showed that this excess was significantly higher than that expected under neutrality and a bottleneck during the Last Glacial Maximum followed by population expansion at the Pleistocene/Holocene boundary or shortly after best explains the correlated sequence patterns. These results indicate that despite recent large demographic changes in the three boreal species from two continents, species-specific selection signatures could still be detected from the analysis of nearly complete regulatory gene sequences. Such different signatures indicate differential subfunctionalization of gene family members in the three congeneric species. PMID- 20354852 TI - Resident motivations and willingness-to-pay for urban biodiversity conservation in Guangzhou (China). AB - The monetary assessment of biodiversity measures the welfare damages brought by biodiversity losses and the cost-benefit analysis of conservation projects in a socio-economic context. The contingent valuation method could include motivational factors to strengthen economic analysis of nature conservation. This study analyzed Guangzhou residents' motivations and willingness-to-pay (WTP) for an urban biodiversity conservation program in the National Baiyun Mountain Scenic Area (BMSA). The peri-urban natural site, offering refuge to some endemic species, is under increasing development pressures for recreational and residential use. A questionnaire survey was conducted in the Guangzhou metropolitan area during June to October 2007. We interviewed face-to-face 720 stratified sampled households to probe residents' attitudes towards the city's environmental issues, motivations for urban nature conservation, and WTP for biodiversity conservation. Principal component analysis identified five motivational factors, including environmental benefit, ecological diversity, nature-culture interaction, landscape-recreation function, and intergenerational sustainability, which illustrated the general economic values of urban nature. Logistic regression was applied to predict the probability of people being willing to pay for the urban biodiversity conservation in BMSA. The significant predictors of WTP included household income and the factor nature-culture interaction. The median WTP estimated RMB149/household (about US$19.5/household) per year and an aggregate of RMB291 million (approximately US$38.2 million) annually to support the urban conservation project. Including public motivations into contingent valuation presents a promising approach to conduct cost-benefit analysis of public projects in China. PMID- 20354853 TI - Assessing the effects of management alternatives on habitat suitability in a forested landscape of northeastern China. AB - Forest management often has cumulative, long-lasting effects on wildlife habitat suitability and the effects may be impractical to evaluate using landscape-scale field experiments. To understand such effects, we linked a spatially explicit landscape disturbance and succession model (LANDIS) with habitat suitability index (HSI) models to assess the effects of management alternatives on habitat suitability in a forested landscape of northeastern China. LANDIS was applied to simulate future forest landscape changes under four management alternatives (no cutting, clearcutting, selective cutting I and II) over a 200-year horizon. The simulation outputs were linked with HSI models for three wildlife species, the red squirrel (Sciurus vulgaris), the red deer (Cervus elaphus) and the hazel grouse (Bonasa bonasia). These species are chosen because they represent numerous species that have distinct habitat requirements in our study area. We assessed their habitat suitability based on the mean HSI values, which is a measure of the average habitat quality. Our simulation results showed that no one management scenario was the best for all species and various forest management scenarios would lead to conflicting wildlife habitat outcomes. How to choose a scenario is dependent on the trade-off of economical, ecological and social goals. Our modeling effort could provide decision makers with relative comparisons among management scenarios from the perspective of biodiversity conservation. The general simulation results were expected based on our knowledge of forest management and habitat relationships of the species, which confirmed that the coupled modeling approach correctly simulated the assumed relationships between the wildlife, forest composition, age structure, and spatial configuration of habitat. However, several emergent results revealed the unexpected outcomes that a management scenario may lead to. PMID- 20354850 TI - An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA) expressing tumors. AB - PURPOSE: Prostate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies. METHODS: Yeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors. RESULTS: The A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo. CONCLUSION: Of the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study. PMID- 20354854 TI - Understanding the value of local ecological knowledge and practices for habitat restoration in human-altered floodplain systems: a case from Bangladesh. AB - Worldwide there is a declining trend in natural fish catch (FAO, The state of world fisheries and aquaculture. http://www.fao.org/documents/show_cdr.asp?url_file=/docrep/007/y5600e/y5600e00.ht , 2002) and Bangladesh is no exception. The vast inland fisheries of Bangladesh have been declining over the years, largely a result of human alteration of the aquatic habitats arising from human interventions in the floodplain systems such as the establishment of water control structures which favor agricultural production but reduce fish habitats. It can be assumed that conventional management measures are not adequate to conserve natural fisheries and exploring alternative knowledge systems to complement existing management is warranted. This paper focuses on local ecological knowledge and several other local practices held by fishers engaging directly with floodplain ecosystems. These knowledge systems and practices may be valuable tools for understanding ecosystems processes and related changes and developing local level responses to avert negative consequences of such changes. This may help in devising alternatives to ecosystem management and the conservation of floodplain fish habitats of Bangladesh and elsewhere in the world. This study was conducted in a natural depression (locally called beel) and its surrounding floodplain system located in north central Bangladesh which has become highly degraded. The results of the study indicate that the fishers and local users of the floodplain ecosystems are rich in local ecological knowledge concerning the hydrology of the floodplains and small lakes, the habitat preferences of fish, the role of agricultural crops on fish habitats, and the impact of habitat human interventions in aquatic ecosystems. Given the apparent inadequacy of the present management regime, this article argues for an inclusion of local knowledge and practices into habitat management as a more holistic approach to floodplain habitat restoration and conservation that encourages multi-level cooperation and which builds on diversified knowledge systems. PMID- 20354855 TI - DRESS syndrome with fatal results induced by sodium valproate in a patient with brucellosis and a positive cytoplasmic antineutrophilic cytoplasmic antibody test result. AB - DRESS syndrome is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. DRESS syndrome related to valproic acid use is very rarely observed. We present a case of DRESS syndrome induced by sodium valproate, which developed and progressed fatally in a brucellosis patient with a positive c-ANCA test. A 19-year-old female patient presented with fever, cough, jaundice, and rash all over her body. Brucella Coombs test was positive at 1:1280 titers, and the Rose Bengal test was also positive. The involuntary movements were thought to be due to chorea, and the patient was started on sodium valproate 500 mg 2 1, as well as streptomycin 1 g flk 1 1 and tetradox capsules 2 1 for the brucellosis and was discharged. DRESS syndrome was suspected in the patient, and she was taken off sodium valproate and tetradox; N-acetylcysteine, ceftriaxon, prednizolone, and support treatment were started. When sodium valproate is used on its own, it carries no risk of inducing DRESS syndrome. However, in the case presented, another co-morbidity such as brucellosis and c-ANCA positivity was present. We believe that the presence of further co morbidity not yet reported in literature is important from the perspective of the risk of valproate-induced DRESS syndrome. Therefore, if sodium valproate treatment is to be started in patients, especially those with co morbidity, they must be closely monitored with clinical and laboratory observations. At the slightest suspicion of DRESS syndrome, all medication should be ceased immediately and the patient should be placed under continuous observation. PMID- 20354856 TI - A case report of systemic lupus erythematosus combined with Castleman's disease and literature review. AB - Although lymph node enlargement is common in active systemic lupus erythematosus (SLE), lymph node examination is frequently ignored in the diagnosis of SLE. Clinical presentation and abnormal laboratory findings are often sufficient for SLE diagnosis, not to mention that the specific histological finding of lymph node necrosis in SLE is rarely seen, and the follicular hyperplasia is usually considered as nonspecific. However, since the late 1990s, a few cases of SLE lymphadenopathy have been reported exhibiting a Castleman's disease (CD) morphology, which was discovered in lymph node biopsies. Here we report a similar case of SLE combined with CD in a 23-year-old girl who displayed systemic symptoms, including systemic lymphadenopathy and abnormal laboratory findings indicating the active phase of SLE. A biopsy of neck lymphnodes showed histopathological features of CD. The patient responded very well to the prednisolone treatment. Based on the related literature review, we would like to stress the possibility of CD in patients with SLE lymphadenopathy. PMID- 20354857 TI - Sacroiliac joint involvement in psoriasis. AB - Psoriasis is a skin disorder that is associated with arthritis. Sacroiliac joint involvement is considered to be less frequent than the other types of psoriatic arthritis. Additionally, the psoriatic sacroiliitis is considered to be asymmetric in general. We aimed to define the frequency and type of sacroiliac involvement in patients with psoriasis. Patients with psoriasis were included the study. Characteristics of skin, nail and articular involvement were noted. Psoriasis area and severity index was calculated. Antero-posterior pelvic X-rays were obtained and graded by two rheumatologists and a radiologist independently. One hundred and thirty-three patients were included. Thirty-seven of patients (27%) have articular involvement symptomatically. The sacroiliac joint involvement was observed in 34 (26%) of patients. More than one-half of sacroiliac involvement was bilateral while less than one-half was in symptomatic patients regarding sacroiliitis. Fifty-seven percentages of all patients have psoriatic nail involvement. Sacroiliac joint involvement did not show any significant association with psoriatic nail involvement or the severity of skin disease. We found higher frequency of sacroiliac joint involvement and bilateral sacroiliitis in patients with psoriasis. This is in contrast to present information about the association of psoriasis and sacroiliitis. These findings need confirmation by further studies and with more sophisticated techniques such as magnetic resonance imaging. PMID- 20354858 TI - Proteus Takayasu's arteritis with unusual intracranial granulomatosis as initial manifestation. AB - Takayasu's arteritis (TA) is an inflammatory vasculitis of aorta and its branches, its low incidence limited our recognition to this entity. We sometimes can confuse this disease with polyarteritis nodosa and other vasculitis when no conventional "big artery" involved in TA cases. Here we report a 26-year-old man with Takayasu's arteritis who presented with a provisional intracranial granulomatosis first and then saccular aneurysms between celiac trunk and arteria hepatica communis and many other proteus manifestations, which is seldom described before. PMID- 20354859 TI - Comparison the efficacy of phonophoresis and ultrasound therapy in myofascial pain syndrome. AB - The aim of this study is to compare the effect of phonophoresis, ultrasound and placebo ultrasound therapies in the treatment of myofascial pain syndrome (MPS). This is a randomized, double-blind placebo controlled study. Sixty patients (48 women, 12 men, mean age 37.9 +/- 12.2 years) with MPS were included in this study. Patients were allocated into three groups. Group 1(n = 20) was received diclofenac phonophoresis, group 2(n = 20) was received ultrasound and group 3(n = 20) was received placebo ultrasound therapies over trigger points, 10 min a day for 15 session during 3 weeks (1 MHz-1,5 watt/cm2). Additionally, all patients were given neck exercise program including isotonic, isometric and stretching. Patients were assessed by means of pain, range of motion (ROM) of neck, number of trigger points (NTP), algometric measurement and disability. Pain severity was measured by visual analog scale (VAS) and Likert scale. The neck pain disability index (NPDI) was used for assessing disability. Measurements were taken before and after treatment. After treatment, there were statistically significant improvements in pain severity, NTP, pressure pain threshold (PPT), ROM and NPDI scores both in phonophoresis and in ultrasound therapy groups (P < 0.05). Statistically significant increase in cervical lateral flexion and rotation was observed in the placebo US group. While there was no statistically significant improvement in the cervical flexion-extension joint movement, pain levels, number of trigger points and NPDI score, pressure pain threshold (P > 0.05), also there were no significant differences in all parameters between group 1 and 2 (P = 0.05). Both diclofenac phonophoresis and ultrasound therapy were effective in the treatment of patients with MPS. Phonophoresis was not found to be superior over ultrasound therapy. PMID- 20354860 TI - [Importance of molecular diagnostics in Alzheimer dementia. A case report]. AB - Alzheimer's disease (AD) is the most frequent form of dementia worldwide. The increasing incidence of AD is due to the dramatic rise in life expectancy. Generally, AD shows a multifactorial etiology and manifests itself only at an older age. However, a small percentage of cases have a monogenic cause, are inherited as an autosomal dominant trait, and begin much earlier. In these cases, molecular analysis and genetic consultation may make sense. PMID- 20354861 TI - Interaction between a pair of gypsy insulators or between heterologous gypsy and Wari insulators modulates Flp site-specific recombination in Drosophila melanogaster. AB - Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. An Flp technology was used to examine interactions between Drosophila gypsy and Wari insulators in somatic and germ cells. The gypsy insulator consists of 12 binding sites for the Su(Hw) protein, while the endogenous Wari insulator, located on the 3' side of the white gene, is independent from the Su(Hw) protein. Insertion of the gypsy but not Wari insulator between FRT sites strongly blocks recombination between Flp dimers bound to FRT sites located on the same chromatid (recombination in cis) or in sister chromatids (unequal recombination in trans). At the same time, the interaction between Wari and gypsy insulators regulates the efficiency of Flp mediated recombination. Thus, insulators may have a role in controlling interactions between distantly located protein complexes (not only those involved in transcriptional gene regulation) on the same chromosome or on sister chromatids in somatic and germ cells. We have also found that the frequency of Flp-mediated recombination between FRT sites is strongly dependent on the relative orientation of gypsy insulators. Taken together, our results indicate that the interactions between insulators can be visualized by Flp technology and that insulators may be involved in blocking undesirable interactions between proteins at the two-chromatid phase of the cell cycle. PMID- 20354862 TI - Aurora B kinase cooperates with CENP-E to promote timely anaphase onset. AB - Error-free chromosome segregation requires that all chromosomes biorient on the mitotic spindle. The motor protein Centromere-associated protein E (CENP-E) facilitates chromosome congression by mediating the lateral sliding of sister chromatids along existing K-fibers, while the mitotic kinase Aurora B detaches kinetochore-microtubule interactions that are not bioriented. Whether these activities cooperate to promote efficient chromosome biorientation and timely anaphase onset is not known. We here show that the chromosomes that fail to congress after CENP-E depletion displayed high centromeric Aurora B kinase activity. This activity destabilized spindle pole proximal kinetochore microtubule interactions resulting in a checkpoint-dependent mitotic delay that allowed CENP-E-independent chromosome congression, thus reducing chromosome segregation errors. This shows that Aurora B keeps the mitotic checkpoint active by destabilizing kinetochore fibers of polar chromosomes to permit chromosome congression in CENP-E-compromised cells and implies that this kinase normally prevents pole proximal syntelic attachments to allow CENP-E-mediated congression of mono-oriented chromosomes. PMID- 20354863 TI - Epithelial tumors of the lacrimal gland in the Chinese: a clinicopathologic study of 298 patients. AB - OBJECTIVE: To examine the clinicopathologic characteristics and clinical features of epithelial tumors of lacrimal gland in China. METHODS: The retrospective case series study included all 298 patients of epithelial lacrimal gland tumors which had been collected in the ophthalmic pathologic laboratory of the Tongren Hospital Beijing in the study period from 1961 to 2005. RESULTS: Pleomorphic adenomas were the most common tumors (n = 213 (72%)), followed by adenoid cystic carcinoma (n = 58 (20%)), pleomorphic adenocarcinoma (n = 13 (4%)), primary adenocarcinoma (n = 8 (3%)) and other tumors (n = 6 (2%)). The most frequent symptoms and clinical signs were restrictions of the lid or eye motility (121 patients; 41%), any other kind of lid involvement (71 patients; 24%), swelling (57 patients; 19%), pain (57 patients; 8%), and decrease in vision (15 patients; 5%). A restriction of the eye motility was noted for 61 patients (21%), due to an involvement of the extraocular muscles with the tumor and due to a tumor-induced displacement of the globe. Apart from the duration of symptoms, the tumor types did not vary significantly in age, gender, and laterality. CONCLUSIONS: Based on the archives of the Beijing Tongren ophthalmo-pathological laboratory, the most common epithelial tumors of the lacrimal gland in mainland China were pleomorphic adenomas, followed by adenoid cystic carcinoma. The spectrum and clinical signs of epithelial lacrimal gland tumors did not differ markedly between Chinese patients and Caucasian patients. PMID- 20354864 TI - Expression of renal and intestinal Na/Pi cotransporters in the absence of GABARAP. AB - We have recently shown that the abundance of the renal sodium (Na)/inorganic phosphate (Pi) cotransporter NaPi-IIa is increased in the absence of the GABA(A) receptor-associated protein (GABARAP). Accordingly, GABARAP-deficient mice have a reduced urinary excretion of Pi. However, their circulating levels of Pi do not differ from wild-type animals, suggesting the presence of a compensatory mechanism responsible for keeping serum Pi values constant. Here, we aimed first to identify the molecular basis of this compensation by analyzing the expression of Na/Pi cotransporters known to be expressed in the kidney and intestine. We found that, in the kidney, the upregulation of NaPi-IIa is not accompanied by changes on the expression of either NaPi-IIc or PiT2, the other cotransporters known to participate in renal Pi reabsorption. In contrast, the intestinal expression of NaPi-IIb is downregulated in mutant animals, suggesting that a reduced intestinal absorption of Pi could contribute to maintain a normophosphatemic status despite the increased renal retention. The second goal of this work was to study whether the alterations on the expression of NaPi-IIa induced by chronic dietary Pi are impaired in the absence of GABARAP. Our data indicate that, in response to high Pi diets, GABARAP-deficient mice downregulate the expression of NaPi-IIa to levels comparable to those seen in wild-type animals. However, in response to low Pi diets, the upregulation of NaPi-IIa is greater in the mutant mice. Thus, both the basal expression and the dietary induced upregulation of NaPi-IIa are increased in the absence of GABARAP. PMID- 20354866 TI - A virulent parent with probiotic progeny: comparative genomics of Escherichia coli strains CFT073, Nissle 1917 and ABU 83972. AB - Escherichia coli is a highly versatile species encompassing a diverse spectrum of strains, i.e. from highly virulent isolates causing serious infectious diseases to commensals and probiotic strains. Although much is known about bacterial pathogenicity in E. coli, the understanding of which genetic determinants differentiates a virulent from an avirulent strain still remains limited. In this study we designed a new comparative genomic hybridization microarray based on 31 sequenced E. coli strains and used it to compare two E. coli strains used as prophylactic agents (i.e. Nissle 1917 and 83972) with the highly virulent uropathogen CFT073. Only relatively minor genetic variations were found between the isolates, suggesting that the three strains may have originated from the same virulent ancestral parent. Interestingly, Nissle 1917 (a gut commensal strain) was more similar to CFT073 with respect to genotype and phenotype than 83972 (an asymptomatic bacteriuria strain). The study indicates that genetic variations (e.g. mutations) and expression differences, rather than genomic content per se, contribute to the divergence in disease-causing ability between these strains. This has implications for the use of virulence factors in epidemiological research, and emphasizes the need for more comparative genomic studies of closely related strains to compare their virulence potential. PMID- 20354867 TI - Multimedia article. Per-oral dual scope NOTES cholecystectomy in porcine model (with video). AB - BACKGROUND: Several working groups have already demonstrated the feasibility of transgastric surgery procedures using flexible endoscopes. However, technical limitations in natural orifice translumenal endoscopic surgery (NOTES) (e.g., exposure, retraction, insufflations, and triangulation) currently still require the use of at least one external instrument. Therefore, "pure NOTES" transgastric cholecystectomy has not yet been described. The authors successfully performed "pure NOTES" transgastric cholecystectomy using a transoral dual-scope technique (similar to the approach the authors previously reported for gastric closure) that allows completion of the procedure by pure NOTES without an external instrument. METHODS: With the subject under general anesthesia, a double-channel gastroscope (Storz(r), Tuttlingen, Germany) passed by mouth entered the peritoneum through the distal anterior gastric wall. The most ideal site for a second gastric exit was then selected for another single-channel scope. With the gallbladder retracted by the assistant operating the double-channel scope, retrograde cholecystectomy was performed by the primary surgeon using the single channel scope. Four animals were killed immediately to study the quality of the operative dissection, whereas the other four pigs were kept alive. The gastrotomy was closed using a 27- to 30-mm cardiac septal occluder (Occlutech(r), GmbH, Jena, Germany) according to a previously described method. The postoperative follow-up assessment of these animals included laparoscopy and necropsy 2 weeks later. RESULTS: All the cholecystectomies were immediately successful without any intraoperative complication. Scope withdrawal caused no injuries to the esophagus or pharynx. Although no overt postoperative complication was evident, two surviving pigs had signs of minor peritoneal infection. CONCLUSIONS: This study investigated "pure NOTES" transgastric cholecystectomy using tentative experimentation to overcome the "retraction" and "triangulation" issues and to realize a "pure NOTES" operation. The use of two endoscopes with selected differentiation of their gastric placements compensated for the lack of triangulation and retraction. PMID- 20354865 TI - Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of Ito channel complex. AB - DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined. In this study, we investigated the functional relevance of DPP10 glycosylation in modulating Kv4.3 channel activities. Using transfected Chinese hamster ovary (CHO) cells to reconstitute Kv4 complex, we show that the pharmacological inhibition of DPP10 glycosylation by tunicamycin and neuraminidase affects transient outward potassium current (I (to)) kinetics. Tunicamycin completely blocked DPP10 glycosylation and reduced DPP10 cell surface expression. The accelerating effects of DPP10 on Kv4.3 current kinetics, i.e. on inactivation and recovery from inactivation, were abolished. Neuraminidase produced different effects on current kinetics than tunicamycin, i.e., shifted the voltage dependence to more negative potentials. The effects of tunicamycin on the native I (to) currents of human atrial myocytes expressing DPP10 were similar to those of the KV4.3/KChIP2/DPP10 complex in CHO cells. Our results suggest that N-linked glycosylation of DPP10 plays an important role in modulating Kv4 channel activities. PMID- 20354868 TI - In vivo thermography during small bowel fusion using radiofrequency energy. AB - BACKGROUND: Radiofrequency-controlled tissue fusion is a novel technology but the associated lateral thermal damage has not been determined. METHODS: Lateral thermal spread of in vivo and ex vivo bowel in a live porcine model fused by radiofrequency energy was evaluated using dynamic infrared thermography and histology. RESULTS: Mean maximum thermal spread measured on histology was <1.2 mm, with no significant difference between thermal spreads for in vivo and ex vivo bowel for radiofrequency energy delivered at 50 V (p = 0.98) and 100 V (p = 0.85). Mean total maximum thermal spread measured by dynamic infrared thermography was <3.9 mm wide on both sides of the instrument with no significant difference between thermal spreads for in vivo and ex vivo bowel for radiofrequency energy delivered at 50 V (p = 0.34) and 100 V (p = 0.19). Fusion quality for in vivo tissue was better when radiofrequency energy was delivered at 100 V compared with 50 V. However, thermal spread measurements and maximum temperatures reached in the tissue were similar in well- and poorly fused bowel. Thermal changes in well-fused bowel were more uniform throughout the different bowel wall layers, whereas in poorly fused tissues, the mucosa did not show thermally induced changes. There were no significant differences between the maximum temperatures detected for in vivo and ex vivo bowel for radiofrequency energy delivered at 50 V (p = 0.25) and 100 V (p = 0.14). CONCLUSIONS: The total thermal changes at both sides of fused bowel are <3.9 mm. The heat sink effect of the application instrument overshadowed any effects of perfusion on limiting thermal spread. Also, using greater amounts of radiofrequency energy at 100 V to achieve better quality fusion does not necessarily increase lateral thermal damage compared with 50 V. PMID- 20354869 TI - Transgastric cecectomy in canine models: natural orifice transluminal endoscopic surgery (NOTES). AB - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) for bowel resection is a challenging procedure. We studied the feasibility and safety of NOTES by performing cecectomy in dogs, which is equivalent to simple bowel resection in man. METHODS: Three dogs underwent transgastric endoscopic cecectomy with laparoscopic assistance. Antibiotics and irrigation were administered as preoperative preparation. A single-channel endoscope was introduced through the stomach into the peritoneal cavity, and the cecum was dissected and ligated with an L-knife and endoloops, respectively. Laboratory blood testing, peritoneal bacterial culture, and radiologic testing were performed perioperatively. Animals underwent autopsies on postoperative day (POD) 14. RESULTS: All subjects survived surgery and remained alive until POD 14. Mean operative time was 126.6 min. The absence of bacterial infections and anatomic leaks was verified by peritoneal swap culture, blood count, air leak testing, and bowel contrast radiology. However, a temporary mild elevation in white blood cell count was noted. No abscess or sign of infection was observed during autopsy, although adhesion was evident. CONCLUSIONS: Transgastric endoscopic cecectomy with minimal laparoscopic assistance is a feasible and safe procedure. Cecectomy in dogs is equivalent to procedures such as appendectomy, resection of Meckel's diverticulum, and oophorectomy in man. Natural orifice transluminal endoscopic surgery could prove to be a good optional surgical procedure. PMID- 20354870 TI - Artificial tactile feedback can significantly improve tissue examination through remote palpation. AB - BACKGROUND: In laparoscopy, impaired feedback information from the operation site and reduced instrument dexterity lead to high demands on surgeons' skill and experience. Pre-clinical studies have shown that artificial tactile feedback (ATF) could significantly improve the quality of tactile feedback information. Additional information about interaction effects of tissue features when using ATF as well as related detection thresholds would be valuable for drawing conclusions on possible clinical application scenarios. OBJECTIVE: To identify surgical procedures in laparoscopy that could benefit from ATF in tissue examination through remote palpation. METHODS: We have developed a laparoscopic grasper capable of providing ATF by measuring the pressure distribution on one forceps jaw with a tactile sensor array. The data was presented graphically on the endoscopic screen. We conducted a study among surgeons and non-surgeons, comparing the capability to detect hidden objects through remote palpation with and without ATF. The data were analyzed using repeated-measures multiple analysis of variance (MANOVA) in two designs. RESULTS: ATF could enhance feedback information with significant positive effects on accuracy, speed, the reduction of the number of grasps, and user confidence. The positive effect of ATF turned out to be especially strong if hidden objects were either hard and too small or large and too soft to be recognized by remote palpation without ATF. CONCLUSIONS: Our study contributes to the discussion on promising application scenarios of ATF enhanced instrumentation in laparoscopic surgery. Based on our study results, such instrumentation may be valuable for detection and examination of hidden bodies or structures through remote palpation. PMID- 20354871 TI - Transcylindrical gas-free cholecystectomy for the treatment of cholelithiasis, cholecystitis, and choledocholithiasis. AB - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the standard for treatment of uncomplicated cholecystolithiasis. However, in cases of cholecystitis or cholecysto-choledocholithiasis, technical and skill requirements may make questionable the convenience of laparoscopy. Transcylindrical cholecystectomy (TC) is a modified minilaparotomy, performed gas-free through a single cylinder 3.8 cm in diameter and 10.0 cm in length. Our study objective has been to assess the efficacy and potential advantages of TC in the treatment of cholelithiasis, cholecystitis, and cholecholithiasis through an efficacy, prospective, and longitudinal study. METHOD: TC was carried out in 364 consecutive patients including 78 acute cholecystitis, 37 acute biliary pancreatitis, and 48 suspected choledocholithiasis. Transcystic cholangiography was selectively attempted in 74 patients (20.3%) and successfully obtained in all but one patient. Twenty-six patients (7.1%) underwent transcylindrical common duct exploration (and calculi removal) through a choledochotomy. RESULTS: Operation was converted into subcostal laparotomy in other 23 patients (5.9%). In our series, there were no injuries to the main bile ducts or hemorrhagic accidents. Operating times in minutes (SD) were (i) "simple cholecystectomy" without cholangiography n = 237: 43.5 (13.3), with cholangiography n = 30: 64.2 (20.7), (ii) "cholecystitis" n = 78: 66.2 (28.7), and (iii) "choledocholithiasis" n = 26: 117.0 (24.6). Postoperative complications for the respective patients in groups i, ii, and iii were (a) wound infection: 5 (1.9%), 0 and 0; (b) bile leaks: 2 (0.75%; one causing death), 2 (0.75%) and 0; (c) reoperation for bleeding: 1 (0.4%), 0 and 1 (3.8%); and (d) residual stones in the main bile ducts: 0, 0 and 1 (3.8%). CONCLUSION: TC has been proved to be applicable, efficient, and safe for the treatment of cholelithiasis and its complications. PMID- 20354872 TI - Hope from Japan for esophagogastric cancers: esophagectomy and endoscopic submucosal dissection for gastric tube cancer. PMID- 20354873 TI - Endoscopic submucosal dissection for remnant gastric cancer. PMID- 20354874 TI - Laparoscopic colorectal cancer resection: examining lymph nodes or standardizing surgery? PMID- 20354875 TI - Sparing minilaparotomy in robotic low anterior resection for cancer. PMID- 20354876 TI - High-quality clinical practice: laparoscopic rectal cancer resection. PMID- 20354877 TI - Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting. AB - BACKGROUND: Epidermal growth factor (EGF) stimulates tumor growth directly via tumor cell EGF receptors or indirectly via its proangiogenic effects. This study's purpose was to determine the impact of minimally invasive colorectal resection (MICR) on postoperative (postop) plasma EGF levels in the colorectal cancer (CRC) and benign disease settings and to see if preoperative (PreOp) EGF levels are altered in cancer patients. METHODS: MICR patients with benign pathology (n = 40) and CRC (n = 48) had blood samples taken PreOp and on postoperative days (POD) 1 and 3. In some patients, late samples were taken between POD7 and POD60; these were bundled into 7-day blocks and considered as single time points. EGF levels were determined by enzyme-linked immunosorbent assay (ELISA) and results were reported as mean +/- SD after logarithmic transformation. The Student t test was used (p < 0.008 after Bonferroni correction). RESULTS: The cancer and benign groups were comparable except for age. The mean PreOp CRC plasma EGF level (122.9 +/- 75.9 pg/ml) was significantly higher than that of the benign group (85.3 +/- 38.5 pg/ml) (p = 0.015). The cancer group's EGF levels were significantly decreased on POD1 and POD3 and for the POD31-55 time point (mean EGF level = 63.1 +/- 42.2 (n = 10). The benign group's POD3 and POD7-14 EGF levels were significantly lower than the PreOp level; later levels returned toward baseline. Small late sample size limited analysis. CONCLUSION: Plasma EGF levels are significantly higher in cancer patients. MICR is associated with a significant decrease in EGF levels early postop in both cancer and benign settings. Unlike the benign group, EGF blood levels in cancer patients remain low during the second postop month. A larger study with more late samples is needed to verify these results. EGF may have value as a tumor marker. PMID- 20354878 TI - Stress impairs psychomotor performance in novice laparoscopic surgeons. AB - BACKGROUND: Little is known about acute stress in surgery although it is recognized to impair human performance in safety-critical industries. This study aimed to establish a direct empirical link between stress and psychomotor performance of novice surgeons. METHODS: Eighteen participants completed this cross-sectional study. Participants carried out laparoscopic tasks on a MIST-VR simulator. Validated dexterity parameters were obtained from MIST-VR (path length, time taken, number of errors). Stress was assessed using the validated Imperial Stress Assessment Tool (ISAT). This captured stress subjectively using the State Trait Anxiety Inventory (STAI) questionnaire and objectively using salivary cortisol and mean and maximum heart rate. RESULTS: Regarding technical performance, median values obtained were 55.12 s (range = 22.9-99.8) for time taken, 4.83 (range = 3-7) for economy of motion, and 88.0 (range = 35-175) for number of errors made. Subjective stress (STAI) correlated with economy of motion (r = 0.53, p = 0.042) and number of errors (r = 0.51, p = 0.034). Objective stress (mean and maximum heart rate) correlated with time taken (r = 0.62, p = 0.004), economy of motion (r = 0.55, p = 0.048), and number of errors (r = 0.67, p = 0.012). CONCLUSION: This is the first study to demonstrate through direct correlation that stress impairs surgical performance on a simulator. Training in managing stress may be required to minimize these deleterious consequences and improve patient care. PMID- 20354881 TI - Minimally invasive colorectal resection for cancer is associated with a short lived decrease in soluble Tie-2 receptor levels, which may transiently inhibit VEGF-mediated angiogenesis (via altered blood levels of free Ang-1 and Ang-2). AB - BACKGROUND: Angiopoetin- (Ang-) 1 inhibits and Ang-2 promotes VEGF-mediated angiogenesis via binding to endothelial cell-bound Tie-2 receptor (Tie-2). After minimally invasive colorectal resection (MICR), Ang-1 levels decrease and Ang-2 levels increase, which may stimulate angiogenesis in wounds and residual tumor foci. Soluble Tie-2 (sTie-2) modulates the effects of free Ang-1 and Ang-2 by binding to them. This study assessed perioperative MICR plasma sTie-2 levels. METHODS: Blood samples were taken preoperatively (PreOp) and on postoperative days (POD) 1 and 3 from 50 cancer and 53 benign disease MICR patients. In a subgroup, a fourth sample was taken between POD7 and POD13 and bundled as a single time point. sTie-2 levels (ng/ml) were determined via ELISA. The mean and SD were determined at each time point. The t test used for analysis. RESULTS: PreOp plasma sTie-2 levels were significantly higher in the benign group (27.6 +/ 10.2) than in the cancer group (22.9 +/- 7.9). A significant drop from PreOp occurred in sTie-2 levels in the cancer group on POD1 (20.0 +/- 7.4) and POD3 (21.0 +/- 6.6) and in the benign group on POD1 (24.8 +/- 9.1). The benign group's POD3 and the cancer group's POD7-13 sTie-2 levels were statistically similar to the PreOp levels while the benign group's POD7-13 level was significantly higher. CONCLUSION: PreOp sTie-2 levels were significantly lower in cancer patients. MICR is associated with a significant short-lived decrease in plasma sTie-2 levels in cancer patients on POD1 and 3, which may briefly inhibit VEGF-mediated angiogenesis. The benign group's early results were similar. PMID- 20354883 TI - Keeping it simple: a "two-step" approach for the fetoscopic correction of spina bifida. PMID- 20354882 TI - Significance of intraoperative endoscopy in total gastrectomy for gastric cancer. AB - BACKGROUND: Anastomotic impairment can be a major cause of surgical complications in gastrointestinal surgery. The aim of this study was to evaluate the efficacy of intraoperative endoscopy (IOE) in esophagojejunal anastomosis for detection of anastomotic impairment. METHODS: Forty-eight patients who underwent total gastrectomy were evaluated for the integrity of the esophagojejunostomy using IOE at completion of mechanical esophagojejunal anastomosis. RESULTS: Overall postoperative anastomotic leakage (PAL) rate was 4.2% (n = 2/48). Both patients who developed PAL had abnormal findings such as mucosal defect in the esophageal mucosa or incomplete anastomotic stapling. Also, IOE revealed inadvertent anastomotic failure in three patients: two jejunal and one esophageal occlusion. There were no complications due to IOE. CONCLUSION: IOE is safe and may easily provide significant information that can minimize PAL by detecting anastomotic failure on esophagojejunal anastomosis. PMID- 20354884 TI - Management of postgastric bypass noninsulinoma pancreatogenous hypoglycemia. AB - INTRODUCTION: Postgastric bypass noninsulinoma hyperinsulinemic pancreatogenous hypoglycemia defines a group of patients with postprandial neuroglycopenic symptoms similar to insulinoma but in many cases more severe. There are few reports of patients with this condition. We describe our surgical experience for the management of this rare condition. METHODS: A retrospective study was performed at St. Vincent Hospital, Indianapolis. Fifteen patients were identified with symptomatic postgastric bypass hypoglycemia for the period 2004-2008. All patients were initially treated with medical therapy for hypoglycemia. Nine patients eventually underwent surgical treatment. The preoperative workup included triple-phase contrast CT scan of the abdomen, endoscopic ultrasound of the pancreas, a 72-h fast followed by a mixed meal test, and calcium-stimulated selective arteriography. Intraoperative pancreatic ultrasound also was performed in all patients. Patients then underwent thorough abdominal exploration, exploration of the entire pancreas, and extended distal pancreatectomy. RESULTS: Nine patients underwent surgery. The mean duration of symptoms was 14 months. The 72-h fast was negative in eight patients (as expected). Triple-phase contrast CT scan of the abdomen was negative in eight patients and showed a cyst in the head of pancreas in one patient. Extended distal (80%) pancreatectomy was performed in all nine patients. The procedure was attempted laparoscopically in eight patients but was converted to open in three. One patient had an open procedure from start to finish. Pathology showed changes compatible with nesidioblastosis with varying degrees of hyperplasia of islets and islet cells. Follow-up ranged from 8-54 (median, 22) months. All patients initially reported marked relief of symptoms. Over time, two patients had complete resolution of symptoms; three patients developed occasional symptoms (once or twice per month), which did not require any medication; two patients developed more frequent symptoms (more than twice per month), which were controlled with medications; and two patients had severe symptoms refractory to medical therapy (calcium channel blockers, diazoxide, octreotide). DISCUSSION: Postprandial hypoglycemia after gastric bypass surgery with endogenous hyperinsulinemia is being increasingly recognized and reported in the literature. Our experience with nine patients is one of the largest. The etiology of this condition is not entirely understood. There may be yet unknown factors involved but increased secretion of glucagon-like peptide 1 and decreased grehlin are being implicated in islet cell hypertrophy. There is no "gold standard" treatment-medical or surgical-but distal pancreatectomy to debulk the hypertrophic islets and islet cells is the main surgical modality in patients with severe symptoms refractory to medical management. PMID- 20354885 TI - Laparoscopic adjustable gastric banding via pars flaccida versus perigastric positioning: technique, complications, and results in 2,549 patients. AB - AIM: Retrospective multicenter analysis of the results of two different approaches for band positioning: perigastric and pars flaccida. METHODS: Data were collected from the database of the Italian Group for LapBand (GILB). Patients operated from January 2001 to December 2004 were selected according to criteria of case-control studies to compare two different band positioning techniques: perigastric (PG group) and pars flaccida (PF group). Demographics, laparotomic conversion, postoperative complications, and weight loss parameters were considered. Data are expressed as mean +/- standard deviation. RESULTS: 2,549 patients underwent the LapBand System procedure [age: 40 +/- 11.7 years; sex: 2,130 female, 419 male; body mass index (BMI): 46.4 +/- 6.9 kg/m(2); excess weight (EW): 60.1 +/- 23.6 kg; %EW: 90.1 +/- 32.4]. During this period 1,343/2,549 (52.7%) were operated via the pars flaccida (PF group) and 1,206/2,549 (47.3%) via the perigastric approach (PG group). Demographics for both groups were similar. Thirty-day mortality was absent in both groups. Operative time was significantly longer in the PG group (80 +/- 20 min versus 60 +/- 40 min; p < 0.05). Hospital stay was similar in the two groups (2 +/- 2 days). Laparotomic conversion was significantly higher in the PG group (6 versus 2 patients; p < 0.001). Overall postoperative complication rate was 172/2,549 (6.7%) and was linked to gastric pouch dilation/slippage (67/172), intragastric migration/erosion (17/172), and tube/port failure (88/172). Gastric pouch dilation and intragastric migration were significantly more frequent in the PG group: 47 versus 20 (p < 0.001) and 12 versus 5 (p < 0.001), respectively. Patients eligible for minimum 3-year follow-up were 1,118/1,206 (PG group) and 1,079/1,343 (PF group). Mean BMI was 33.8 +/- 12.1 kg/m(2) (PG group) and 32.4 +/ 11.7 kg/m(2) (PF group) (p = ns), and mean percentage excess weight loss (%EWL) was 47.2 +/- 25.4 and 48.9 +/- 13.2 in PG and PF groups, respectively (p = ns). CONCLUSIONS: Significant improvement in LapBand System results with regard to laparotomic conversion and postoperative complication rate, with similar weight loss results, was observed in the pars flaccida group. PMID- 20354887 TI - Brain germinoma presenting as a first psychotic episode in an adolescent male. PMID- 20354886 TI - Nanomolar concentrations of cocaine enhance D2-like agonist-induced inhibition of the K+-evoked [3H]-dopamine efflux from rat striatal synaptosomes: a novel action of cocaine. AB - Previous studies have indicated that cocaine binding sites contain both high- and low-affinity binding components and have actions not related to dopamine uptake inhibition. Therefore, it has been studied if concentrations of cocaine in the range of 0.1-100 nM can affect not only dopamine uptake but also the quinpirole induced inhibition of the K(+)-evoked [(3)H]-dopamine efflux from rat striatal synaptosomes. It was found that quinpirole-induced inhibition of K(+)-evoked [(3)H]-dopamine efflux was significantly enhanced by cocaine at 1 and 10 nM but not at 0.1 nM with cocaine alone being inactive and 1 nM cocaine lacking effects on [(3)H]-dopamine uptake in rat striatal synaptosomes. The results indicate the existence of a novel allosteric agonist action of cocaine in low concentrations, not affecting dopamine uptake, at striatal D(2) autoreceptors modulating striatal dopamine transmission. PMID- 20354888 TI - Scanning electron microscopy investigation of PMMA removal by laser irradiation (Er:YAG) in comparison with an ultrasonic system and curettage in hip joint revision arthroplasty. AB - The cement often left in the femur socket during hip joint revision arthroplasty is usually removed by curettage. Another method for removing the cement is to use an ultrasonic system, and yet another alternative may be to use a laser system. The aim of these investigations was to determine the pulse rate and pulse energy of the Er:YAG laser for sufficient cement ablation. We also compared the results obtained using the laser with those obtained using an ultrasonic device or curettage by histological and scanning electron microscopy (SEM) investigation of the border zone between the polymethyl methacrylate (PMMA) and unfixed specimens of femoral bone. Therefore we prepared 30 unfixed human femur stems after hip joint replacement and prepared ten sagittal sections from each femur stem (in total 300 sections). Of these 300 specimens, 180 were treated with the Er:YAG laser, 60 with the ultrasonic system and 60 by curettage. The high pulse energy of 500 mJ and a pulse rate of 4 Hz provided the highest PMMA ablation rate, although the boundary surface between PMMA and femoral bone was not as fine grained as found in samples treated at 15 Hz and 250 mJ. However, the treatment time for the same cement ablation rate with the latter settings was twice that at 4 Hz and 500 mJ. Compared to the boundary surfaces treated with the ultrasonic device or curettage, the laser-treated samples had a more distinct undifferentiated boundary surface between PMMA and femoral bone. After development of the Er:YAG-laser to provide higher pulse energies, it may in the future be an additional efficient method for the removal of PMMA in revision arthroplasty. The Er:YAG laser should be combined with an endoscopic and a rinsing suction system so that PMMA can be removed from the femoral shaft under direct vision. PMID- 20354889 TI - Severe interstitial pneumonitis associated with the administration of taxanes. AB - Interstitial pneumonitis has sporadically been reported as a toxic effect of taxanes such as docetaxel and paclitaxel. This report describes 2 patients who developed interstitial pneumonitis after receiving chemotherapy including taxanes, and both cases grew serious enough to require respiratory support. The first case was a 57-year-old man with gastric cancer treated with docetaxel biweekly and S-1 for 2 weeks as adjuvant chemotherapy. After 4 courses of docetaxel, he presented acute dyspnea. The second case was a 66-year-old woman with breast cancer and postoperative pleural recurrence treated with weekly paclitaxel as fourth-line chemotherapy. She developed a dry cough, high fever, and dyspnea after 1 course of paclitaxel. In both cases, computed tomography (CT) showed extensive bilateral areas of ground-glass attenuation. They developed progressive interstitial infiltrates and respiratory failure that required mechanical ventilation. Taxane-induced interstitial pneumonitis was diagnosed to exclude other causes. From previous reports, intubation is associated with the survival of patients with taxane-induced interstitial pneumonitis. However, corticosteroid therapy was dramatically effective and resolved the interstitial pneumonitis in both our patients. Clinicians should be aware of this occasional complication during the course of chemotherapy with taxanes and initiate treatment, including respiratory support, as soon as possible. PMID- 20354890 TI - Comparison of rifabutin susceptibility and rpoB mutations in multi-drug-resistant Mycobacterium tuberculosis strains by DNA sequencing and the line probe assay. AB - We compared rifabutin susceptibility and rpoB mutations in 98 multi-drug resistant strains of Mycobacterium tuberculosis (MDR-TB) by DNA sequencing and with a line probe assay using the commercially available INNO-LiPA Rif. TB kit (the LiPA). Our results indicated that rifabutin continues to remain active against MDR-TB strains harboring certain genetic alterations and also that the LiPA might be useful in identifying MDR-TB strains susceptible to rifabutin. PMID- 20354892 TI - Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution. AB - Generating the appropriate protonation states of drug-like molecules in solution is important for success in both ligand- and structure-based virtual screening. Screening collections of millions of compounds requires a method for determining tautomers and their energies that is sufficiently rapid, accurate, and comprehensive. To maximise enrichment, the lowest energy tautomers must be determined from heterogeneous input, without over-enumerating unfavourable states. While computationally expensive, the density functional theory (DFT) method M06-2X/aug-cc-pVTZ(-f) [PB-SCRF] provides accurate energies for enumerated model tautomeric systems. The empirical Hammett-Taft methodology can very rapidly extrapolate substituent effects from model systems to drug-like molecules via the relationship between pK(T) and pK(a). Combining the two complementary approaches transforms the tautomer problem from a scientific challenge to one of engineering scale-up, and avoids issues that arise due to the very limited number of measured pK(T) values, especially for the complicated heterocycles often favoured by medicinal chemists for their novelty and versatility. Several hundreds of pre calculated tautomer energies and substituent pK(a) effects are tabulated in databases for use in structural adjustment by the program Epik, which treats tautomers as a subset of the larger problem of the protonation states in aqueous ensembles and their energy penalties. Accuracy and coverage is continually improved and expanded by parameterizing new systems of interest using DFT and experimental data. Recommendations are made for how to best incorporate tautomers in molecular design and virtual screening workflows. PMID- 20354891 TI - Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. AB - OBJECTIVE AND METHODS: This study deals with cardiovascular autonomic neuropathy (CAN) in type 1 diabetic patients and its association with other complications. We searched for CAN in 684 patients (age, 47 +/- 12 years; diabetes duration, 22 +/- 11 years) by cardiovascular responses to deep breathing and standing. Patients considered as positive had laboratory evaluation: "Ewing" tests (deep breathing, Valsalva, stand test, hand grip); heart rate variability (HRV) [low frequency (LF) and high frequency (HF) power] and spontaneous baroreflex slope (SBS). Logistic regression was used to identify the combination of patient characteristics, including other complications, most associated with CAN severity according to Ewing Score (ES 0-5). RESULTS: 66.2% presented no significant abnormality (ES 0-0.5), 21.5 % had mild abnormalities (ES 1-2), and 12.3% had confirmed autonomic failure (ES > 2). Decrease in LF, HF and SBS was highly correlated to CAN severity. In the stepwise regression, age, retinopathy, nephropathy, bladder dysfunction, erectile dysfunction, peripheral neuropathy and hypertension remained correlated with CAN, whereas digestive neuropathy, BMI and HbA1c were excluded. Despite a small number of events, we found a significant association between coronary disorders and CAN severity. CONCLUSIONS: Simple bedside tests can detect CAN. HRV and SBS provide additional elements on CAN severity. Diabetes duration did not discriminate sufficiently patients with CAN. The association with retinopathy is in favor of the role of poor glycemic control in CAN development. This study shows the interest of CAN detection and the need to look for extracardiac autonomic neuropathy and silent myocardial ischemia in patients with confirmed CAN. PMID- 20354893 TI - Predictions of hydration free energies from continuum solvent with solute polarizable models: the SAMPL2 blind challenge. AB - This paper reports the results of our attempt to predict hydration free energies on the SAMPL2 blind challenge dataset. We mostly examine the effects of the solute electrostatic component on the accuracy of the predictions. The usefulness of electronic polarization in predicting hydration free energies is assessed by comparing the Electronic Polarization from Internal Continuum model and the self consistent reaction field IEF-PCM to standard non-polarizable charge models such as RESP and AM1-BCC. We also determine an optimal restraint weight for Dielectric RESP atomic charges fitting. Statistical analysis of the results could not distinguish the methods from one another. The smallest average unsigned error obtained is 1.9 +/- 0.6 kcal/mol (95% confidence level). A class of outliers led us to investigate the importance of the solute-solvent instantaneous induction energy, a missing term in PB continuum models. We estimated values between -1.5 and -6 kcal/mol for a series of halo-benzenes which can explain why some predicted hydration energies of non-polar molecules significantly disagreed with experiment. PMID- 20354895 TI - Variation in and responses to brood pheromone of the honey bee (Apis mellifera L.). AB - The 10 fatty acid ester components of brood pheromone were extracted from larvae of different populations of USA and South African honey bees and subjected to gas chromatography-mass spectrometry quantitative analysis. Extractable amounts of brood pheromone were not significantly different by larval population; however, differences in the proportions of components enabled us to classify larval population of 77% of samples correctly by discriminant analysis. Honeybee releaser and primer pheromone responses to USA, Africanized and-European pheromone blends were tested. Texas-Africanized and Georgia-European colonies responded with a significantly greater ratio of returning pollen foragers when treated with a blend from the same population than from a different population. There was a significant interaction of pheromone blend by adult population source among Georgia-European bees for modulation of sucrose response threshold, a primer response. Brood pheromone blend variation interacted with population for pollen foraging response of colonies, suggesting a self recognition cue for this pheromone releaser behavior. An interaction of pheromone blend and population for priming sucrose response thresholds among workers within the first week of adult life suggested a more complex interplay of genotype, ontogeny, and pheromone blend. PMID- 20354894 TI - Promoter diversity in multigene transformation. AB - Multigene transformation (MGT) is becoming routine in plant biotechnology as researchers seek to generate more complex and ambitious phenotypes in transgenic plants. Every nuclear transgene requires its own promoter, so when coordinated expression is required, the introduction of multiple genes leads inevitably to two opposing strategies: different promoters may be used for each transgene, or the same promoter may be used over and over again. In the former case, there may be a shortage of different promoters with matching activities, but repetitious promoter use may in some cases have a negative impact on transgene stability and expression. Using illustrative case studies, we discuss promoter deployment strategies in transgenic plants that increase the likelihood of successful and stable multiple transgene expression. PMID- 20354896 TI - Induction of phenolic glycosides by quaking aspen (Populus tremuloides) leaves in relation to extrafloral nectaries and epidermal leaf mining. AB - We studied the effect of epidermal leaf mining on the leaf chemistry of quaking aspen, Populus tremuloides, during an outbreak of the aspen leaf miner, Phyllocnistis populiella, in the boreal forest of interior Alaska. Phyllocnistis populiella feeds on the epidermal cells of P. tremuloides leaves. Eleven days after the onset of leaf mining, concentrations of the phenolic glycosides tremulacin and salicortin were significantly higher in aspen leaves that had received natural levels of leaf mining than in leaves sprayed with insecticide to reduce mining damage. In a second experiment, we examined the time course of induction in more detail. The levels of foliar phenolic glycosides in naturally mined ramets increased relative to the levels in insecticide-treated ramets on the ninth day following the onset of leaf mining. Induction occurred while some leaf miner larvae were still feeding and when leaves had sustained mining over 5% of the leaf surface. Leaves with extrafloral nectaries (EFNs) had significantly higher constitutive and induced levels of phenolic glycosides than leaves lacking EFNs, but there was no difference in the ability of leaves with and without EFNs to induce phenolic glycosides in response to mining. Previous work showed that the extent of leaf mining damage was negatively related to the total foliar phenolic glycoside concentration, suggesting that phenolic glycosides deter or reduce mining damage. The results presented here demonstrate that induction of phenolic glycosides can be triggered by relatively small amounts of mining damage confined to the epidermal tissue, and that these changes in leaf chemistry occur while a subset of leaf miners are still feeding within the leaf. PMID- 20354897 TI - Health care professionals' views of sharing information with families who have a child with a genetic condition. AB - The purpose of this study was to examine health care professionals' views and strategies for individualizing information sharing in families who have a child with a genetic condition. The sample consisted of 37 health professionals from three clinical sites in the greater metropolitan area of a large Midwestern city. Qualitative content thematic analysis was used to analyze data from the health professionals' semi-structured interviews. Four themes captured how health care professionals work with families around information management: Sharing Information with Parents, Taking into Account Parental Preferences, Understanding of the Condition, and Helping Parents Inform Others. These findings contribute to understanding the processes that health professionals use in sharing information with parents who have children with a genetic condition, and they provide guidance for clinical practice, professional training, and future research. PMID- 20354898 TI - Calibration of the head direction network: a role for symmetric angular head velocity cells. AB - Continuous attractor networks require calibration. Computational models of the head direction (HD) system of the rat usually assume that the connections that maintain HD neuron activity are pre-wired and static. Ongoing activity in these models relies on precise continuous attractor dynamics. It is currently unknown how such connections could be so precisely wired, and how accurate calibration is maintained in the face of ongoing noise and perturbation. Our adaptive attractor model of the HD system that uses symmetric angular head velocity (AHV) cells as a training signal shows that the HD system can learn to support stable firing patterns from poorly-performing, unstable starting conditions. The proposed calibration mechanism suggests a requirement for symmetric AHV cells, the existence of which has previously been unexplained, and predicts that symmetric and asymmetric AHV cells should be distinctly different (in morphology, synaptic targets and/or methods of action on postsynaptic HD cells) due to their distinctly different functions. PMID- 20354899 TI - Anxiety and depression in children with HFASDs: symptom levels and source differences. AB - The purpose of this study was to: (1) examine symptom levels of anxiety and depression in children with high-functioning autism spectrum disorders (HFASDs) compared with matched control children using child self-reports and parent ratings; and (2) examine source differences within the two condition groups. An overall multivariate effect indicated significantly elevated depression and anxiety symptoms for children with HFASDs based on parent reports; however no significant between-group differences based on child self-reports. Within condition source comparisons (parent vs. child) revealed a significant multivariate effect indicating a significant difference in symptoms of depression and anxiety for the HFASD group but none for the control. Correlations between parent and child reports for the HFASD group suggested some positive association between child-reports and parent-reports for depressive symptoms only; however, the difference in average scores reflected a substantial discrepancy in the magnitude of symptoms by rater. Implications for clinical assessment and future research are provided. PMID- 20354900 TI - Development of a microalgal PAM test method for Cu(II) in waters: comparison of using spectrofluorometry. AB - Test methods are needed to monitor Cu concentrations in reservoirs and water supplies. Dictyosphaerium chlorelloides (Chlorophyta) cells were immobilized in a silicate sol-gel and the toxic effects of Cu(II) were examined using different techniques: fluorescence measurements (using a spectrofluorometer with an optic fiber coupled to a flow cell or a 96-well-plate reader) or by Pulse Amplitude Modulation (PAM) parameters using a portable instrument and the pulse saturation method. Fm' and qN were the most sensitive indicator parameters when performing Cu analysis in water. D. chlorelloides PAM biosensor presented a detection limit of 0.6 mg l(-1) for Cu(II), within the limits to establish if Cu concentrations exceeded regulatory levels. Moreover, a 1.9 mg Cu l(-1) (30 microM) resistant strain of the D. chlorelloides microalgae was produced in order to obtain more selectivity on the metal determination. PMID- 20354901 TI - Acute kidney injury secondary to renal large B-cell lymphoma: role of early renal biopsy. AB - Renal involvement in large B-cell lymphoma represents an exceptional manifestation of non-Hodgkin lymphomas. Acute kidney injury (AKI) by lymphomatous infiltration is extremely rare and so far only 19 cases have been reported in the literature. We report a 67-year-old woman who presented with AKI and was found to have large B-cell lymphoma infiltrating her kidneys. The patient was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab, and a dramatic improvement of renal function was noticed after two weeks of treatment. Her renal function completely recovered after four weeks of treatment. In conclusion, lymphomatous infiltration of kidneys can directly lead to AKI. Rapid diagnosis and treatment is essential to preserve the renal function. Renal biopsy is the gold standard for the early diagnosis of non-Hodgkin lymphoma as a cause of AKI. PMID- 20354902 TI - Estimating dynamic gait stability using data from non-aligned inertial sensors. AB - Recently, two methods for quantifying the stability of a dynamical system have been applied to human locomotion: local stability (quantified by finite time maximum Lyapunov exponents, lambda(s) and lambda(L)) and orbital stability (quantified by maximum Floquet multipliers, MaxFm). In most studies published to date, data from optoelectronic measurement systems were used to calculate these measures. However, using wireless inertial sensors may be more practical as they are easier to use, also in ambulatory applications. While inertial sensors have been employed in some studies, it is unknown whether they lead to similar stability estimates as obtained with optoelectronic measurement systems. In the present study, we compared stability measures of human walking estimated from an optoelectronic measurement system with those calculated from an inertial sensor measurement system. Subjects walked on a treadmill at three different speeds while kinematics were recorded using both measurement systems. From the angular velocities and linear accelerations, lambda(s), lambda(L), and MaxFm were calculated. Both measurement systems showed the same effects of walking speed for all variables. Estimates from both measurement systems correlated high for lambda(s) and lambda(L,) (R > 0.85) but less strongly for MaxFm (R = 0.66). These results indicate that inertial sensors constitute a valid alternative for an optoelectronic measurement system when assessing dynamic stability in human locomotion, and may thus be used instead, which paves the way to studying gait stability during natural, everyday walking. PMID- 20354903 TI - Construction of cDNA library and preliminary analysis of expressed sequence tags from green microalga Ankistrodesmus convolutus Corda. AB - Green microalga Ankistrodesmus convolutus Corda is a fast growing alga which produces appreciable amount of carotenoids and polyunsaturated fatty acids. To our knowledge, this is the first report on the construction of cDNA library and preliminary analysis of ESTs for this species. The titers of the primary and amplified cDNA libraries were 1.1*10(6) and 6.0*10(9) pfu/ml respectively. The percentage of recombinants was 97% in the primary library and a total of 337 out of 415 original cDNA clones selected randomly contained inserts ranging from 600 to 1,500 bps. A total of 201 individual ESTs with sizes ranging from 390 to 1,038 bps were then analyzed and the BLASTX score revealed that 35.8% of the sequences were classified as strong match, 38.3% as nominal and 25.9% as weak match. Among the ESTs with known putative function, 21.4% of them were found to be related to gene expression, 14.4% ESTs to photosynthesis, 10.9% ESTs to metabolism, 5.5% ESTs to miscellaneous, 2.0% to stress response, and the remaining 45.8% were classified as novel genes. Analysis of ESTs described in this paper can be an effective approach to isolate and characterize new genes from A. convolutus and thus the sequences obtained represented a significant contribution to the extensive database of sequences from green microalgae. PMID- 20354904 TI - Effects of genetic variability of the dairy goat growth hormone releasing hormone receptor (GHRHR) gene on growth traits. AB - Growth hormone-releasing hormone receptor (GHRHR) plays a critical role in growth hormone (GH) synthesis, release and regulation of pituitary somatotroph expansion in vertebrates. The objective of this study was to investigate variations in goat GHRHR gene and their associations with growth traits in 668 dairy goats. The results showed four novel single nucleotide polymorphisms (SNPs): NC_007302:g.5203C>T, 7307C>G, 9583G>A and 9668A>C. In detail, the novel SNP C>T in the 5203rd nucleotide identified a missense mutation: CCC (Pro)>TCC (Phe) at position 116aa of the goat GHRHR (423aa). Besides, 9583G>A and 9668A>C polymorphism were in complete linkage disequilibrium. The genetic diversity analysis revealed that the Guanzhong dairy goat possessed intermediate genetic diversity in P3 and P7 loci, and the Xinong Sannen dairy goat belonged to poor genetic diversity in P4 locus. Significant associations between the genotypes of P3 locus and body length, body height and chest circumference was observed in Guanzhong goat (P<0.05). However, in Xinong saanen population, significant statistical difference was only found in body height and body length (P<0.05). In P4 and P7 loci, no significant associations were detected between any variant sites and body length, body height and chest circumference, as well as for the milk traits (P>0.05). These results strongly suggested that the goat GHRHR gene is a candidate gene that influences growth traits in dairy goat. PMID- 20354905 TI - Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations. AB - The allelic frequencies of apolipoprotein E (apoE) vary substantially around the world. There is a conspicuous south-to-north gradient of e4 frequencies in Europe, with the proportion of e4 carriers from only 10-15% in the south to 40 50% in the north. The mechanism may be related to the possibility that e4 carriers are less likely to develop vitamin D deficiency. In addition, Asian populations traditionally have lower e4 frequency than Europeans, which may be attributed in part to the scarce or irregular food supplies in Western world in the recent past. However, whether these geographical distribution gradients exist in China is yet unknown. ApoE genotypes of 200 children from Nanning City were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. Allele frequency data of 18 other populations were collected from published sources and correlated with latitude and longitude information from different geographic resources. In our subjects, the frequencies of apoE genotypes were E3/E3: 73.0%, E3/E2: 15.0%, E4/E3: 5.0%, E4/E4: 5.0%, and E4/E2: 2.0%; the frequencies of apoE alleles were e2: 8.5%, e3: 83.0%, and e4: 8.5%, respectively. The total sample consisted of 3,679 individuals from 19 Chinese populations; the allelic frequencies were e2: 7.6%, e3: 85.5%, and e4: 6.9%, respectively; the proportion of e4 carriers was from 4.9% in Kunming to 17.5% in Harbin. Systemic comparison among multiple Chinese populations revealed that positive correlation existed between the e4 allele frequency distribution and latitude north (r=0.586, P=0.008), but no correlation of the e4 allele frequency distribution with longitude east was found (r=-0.018, P=0.942). We conclude that there is a south to-north, but not an east-to-west gradient for the apoE4 allele in China. PMID- 20354906 TI - Ectopic expression of a grapevine transcription factor VvWRKY11 contributes to osmotic stress tolerance in Arabidopsis. AB - Plant WRKY transcriptional factors play an important role in response to biotic and abiotic stresses. In this study, a WRKY transcription factor was isolated from grapevine. This transcription factor showed 66% and 58% identity at the DNA and amino acid sequence levels, respectively, with Arabidopsis AtWRKY11 genes, and was therefore designated VvWRKY11. Phylogenetic analysis and structure comparison indicated that VvWRKY11 protein belongs to group IIc. The VvWRKY11 protein was shown to be located in the nucleus based on green fluorescent protein analysis. Yeast one-hybrid analysis further indicated that VvWRKY11 protein binds specifically to the W-box element. The expression profile of VvWRKY11 in response to treatment with phytohormone salicylic acid or pathogen Plasmopara viticola is rapid and transient. Transgenic Arabidopsis seedlings overexpressing VvWRKY11 showed higher tolerance to water stress induced by mannitol than wild-type plants. These results clearly demonstrated that the VvWRKY11 gene is involved in the response to dehydration stress. In addition, the role of VvWRKY11 protein in regulating the expression of two stress response genes, AtRD29A and AtRD29B, is also discussed. PMID- 20354907 TI - Antitumor activity of an adenovirus harboring human IL-24 in colon cancer. AB - Data have increasingly shown that melanoma differentiation associated gene-7 (Mda 7/IL-24) has growth suppression activity and can induce apoptosis in many tumor cells, but to our knowledge there have been few studies about its role in colon cancer. We examined its anti-cancer effect on colon cancer. We constructed a recombinant replication-deficient adenovirus carrying human melanoma differentiation associated gene-7 (Ad-IL-24) and examined its apoptosis-inducing efficacy on the colon cancer HT-29 cell line and on an oxaliplatin-resistant cell line HT-29/oxa, using a combination of flow cytometry, growth suppressive activity by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and xenografts. Furthermore, we tested the suppression activity of Mda-7/IL-24 on vascular endothelial growth factor (VEGF) and microvessel density (MVD), as well as the inductive effect on expression of the growth arrest and DNA damage gene (GADD) in xenograft tumors by immunohistochemistry. Melanoma differentiation associated gene-7 can inhibit the growth of colon cancer cell lines and induced apoptosis in about (5.6+/-0.3)% of HT-29 cells (P<0.05). Xenograft growth was retarded in vivo in mice treated with melanoma differentiation associated gene-7, but the tumor proliferation rate for this group was not significantly different in comparison to controls (P>0.05). Furthermore, melanoma differentiation associated gene-7 induced expression of a growth arrest and DNA damage (GADD) gene and reduced the expression of both VEGF and MVD in xenograft tumors. This study supports a potential therapeutic effect for melanoma differentiation associated gene-7 on colon cancer. PMID- 20354908 TI - Molecular characterization of a phenylalanine ammonia-lyase gene (BoPAL1) from Bambusa oldhamii. AB - Phenylalanine ammonia-lyase is the first enzyme of general phenylpropanoid pathway. A PAL gene, designated as BoPAL1, was cloned from a Bambusa oldhamii cDNA library. The open reading frame of BoPAL1 was 2,139 bp in size and predicted to encode a 712-amino acid polypeptide. BoPAL1 was the first intronless PAL gene found in angiosperm plant. Several putative cis-acting elements such as P box, GT 1motif, and SOLIPs involved in light responsiveness were found in the 5'-flanking sequence of BoPAL1 which was obtained by TAIL-PCR method. Recombinant BoPAL1 protein expressed in Pichia pastoris was active. The optimum temperature and pH for BoPAL1 activity was 50 degrees C and 9.0, respectively. The molecular mass of recombinant BoPAL1 was estimated as 323 kDa using gel filtration chromatography and the molecular mass of full-length BoPAL was about 80 kDa, indicating that BoPAL1 presents as a homotetramer. The Km and kcat values of BoPAL1 for L-Phe were 1.01 mM and 10.11 s(-1), respectively. The recombinant protein had similar biochemical properties with PALs reported in other plants. PMID- 20354910 TI - The contribution of urban foodways to health disparities. AB - How do urban food environments produce health disparities? The literature currently emphasizes the etiologic relevance of urban food deserts and their nutritional shortcomings. This paper instead examines the health relevance of foodways--the social dynamics surrounding the production, purchase, and consumption of food. We report on data from 32 photo-elicitation interviews conducted with adult residents of Philadelphia, examining distinct foodways and health concerns that play out in the most commonly discussed retail establishments: corner stores, "Stop and Go's" (delis that also sell beer), and Chinese takeout restaurants. Corner store visits, described as a routinized element of children's school day, were implicated in early life patterning of unsound nutritional choices. Stop and Go's were described as a health threat because of their alcohol sales and tacit promotion of public drunkenness, coupled with accessibility to youth. Stop and Go's and Chinese takeouts both were perceived as generators of violence in part because of on-site sales of alcohol, drug paraphernalia, and illicit drugs. Chinese takeouts also were described as symbolic reminders of African Americans' economic exclusion and as places infused with race/ethnic tension and hostile merchant-customer interactions. Instead of viewing the food environment simply as a source of calories and nutrients, participants discussed the complex social dynamics that play out therein, raising a range of important considerations for (especially disadvantaged) urban residents' safety, physical well-being, and mental health. PMID- 20354911 TI - What makes a respondent-driven sampling "seed" productive? Example of finding at risk Massachusetts men who have sex with men. AB - Several recent studies have sought to elaborate upon the applicability and validity of respondent-driven sampling (RDS) to find hard-to-reach samples in general and men who have sex with men (MSM) in particular. Few published studies have elucidated the characteristics associated with initial RDS participants ("seeds") who successfully recruited others into a study. A total of 74 original seeds were analyzed from four Massachusetts studies conducted between 2006 and 2008 that used RDS to reach high-risk MSM. Seeds were considered "generative" if they recruited two or more subsequent participants and "non-generative" if they recruited zero or one participant. Overall, 34% of seeds were generative. In separate multivariable logistic regression models controlling for age, race, health insurance, HIV status, and the study for which the seed was enrolled, unprotected anal sex in the past 12 months [adjusted odds ratio (AOR) = 6.68; 95% confidence interval (95% CI) = 1.27-35.12; p = 0.03], cocaine use during sex at least monthly during the past 12 months (AOR = 8.81; 95% CI = 1.68-46.27; p = 0.01), and meeting sex partners at social gatherings (AOR = 7.42; 95% CI = 1.58 34.76; p = 0.01) and public cruising areas (AOR = 4.92; 95% CI = 1.27-19.01; p = 0.02) were each significantly associated with increased odds of being a generative seed. These findings have methodological and practical implications for the recruitment of MSM via RDS. Finding ways to identify RDS seeds that are consistently generative may facilitate collecting a sample that is closer to reflecting the MSM who live in all of the communities in a given location or study sample. PMID- 20354912 TI - Factors affecting a recently purchased handgun's risk for use in crime under circumstances that suggest gun trafficking. AB - While many handguns are used in crime each year in the USA, most are not. We conducted this study to identify factors present at the time of a handgun's most recent retail sale that were associated with its subsequent use in crime under circumstances suggesting that the handgun had been trafficked--purchased with the intent of diverting it to criminal use. Handguns acquired in multiple-gun purchases were of particular interest. Using data for 180,321 handguns purchased from federally licensed retailers in California in 1996, we studied attributes of the handguns, the retailers selling them, the purchasers, and the sales transactions. Our outcome measure was a handgun's recovery by a police agency, followed by a gun ownership trace, conducted by the Bureau of Alcohol, Tobacco, Firearms and Explosives, that determined (a) that the recovery had occurred within 3 years of the handgun's most recent purchase from a licensed retailer and (b) that the person who possessed the gun when it was recovered by police was not its most recent purchaser. Altogether, 722 handguns were recovered and had trace results that met the additional criteria. Handguns acquired in multiple-gun, same day transactions were more likely to be traced than were single-purchase handguns (odds ratio [OR] 1.33, 95% confidence intervals [CI] 1.08 to 1.63). This was not the case for multiple-purchase handguns defined more broadly as multiple handguns purchased by one individual over any 30-day period as used in "one-gun-a-month" laws. Bivariate regressions indicated increased risk of a handgun being traced when it sold new for $150 or less (OR 4.28, 95% CI 3.59 to 5.11) or had been purchased by a woman (OR 2.02, 95% CI 1.62 to 2.52). Handguns sold by retailers who also had a relatively high proportion (>or=2%) of purchases denied because the prospective purchasers were prohibited from owning firearms were more likely to be traced than were those sold by other retailers (OR 4.09, 95% CI 3.39 to 4.94). These findings persisted in multivariate analyses. Our findings suggest specific strategies for intervention to prevent gun violence. PMID- 20354914 TI - Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas. AB - The growth and development of pancreatic islet cells are regulated by various morphogens. Vitamin A modulates in vitro differentiation of islet cells and vitamin D affects beta-cell insulin secretion, while both vitamin ligands act through heterodimerization with the retinoid X receptor (RXR). However, their effects in modulating pancreatic development have not been determined. In this study, cultured human pancreatic progenitor cells (PPCs) isolated from human fetal pancreas were stimulated to differentiate into islet-like cell clusters (ICCs). RT-PCR, Western blotting and immunocytochemistry were used to examine the expression and localization of vitamin D receptor (VDR), retinoic acid receptor (RAR), and RXR in PPCs. The effects of added all-trans retinoic acid (atRA, a form of vitamin A), calcitriol (activated vitamin D) and of these ligands together on PPC cell viability, proliferation and apoptosis were assessed by MTT, BrdU and ELISA assays, respectively. Post-treatment neurogenin-3 (NGN3) expression, necessary for islet-cell lineage development, was examined by real time RT-PCR. Results showed that RAR, RXR and VDR were expressed in PPCs. RAR and RXR were localized in nuclei, and the VDR in nuclei, cytoplasm and plasma membrane. atRA and calcitriol each increased PPC viability and proliferation; atRA additionally decreased PPC apoptosis. Co-addition of atRA and calcitriol had no additive effects on cell viability but did increase ngn3 responses. In conclusion, RAR, RXR and VDR are expressed in human fetal PPCs and PPC proliferation can be promoted by calcitriol, atRA or both together, data valuable for elucidating mechanisms underlying islet development and for developing clinical islet transplantation. PMID- 20354915 TI - Hyperpolarization induces differentiation in human cardiomyocyte progenitor cells. AB - In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. These cells can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells and are therefore of great value for investigation of the mechanisms that drive progenitor cell function and plasticity, drug testing and, potentially, therapeutical purposes. In this respect, most studies have focused on enhancing differentiation with chemicals or growth factors, or co-culture with other cell types. Although they have revealed important mechanisms, protocols need to be established that exclude the need for such factors when one considers using progenitor cells to repair the human heart. In this study we tested whether we could induce cardiomyogenic differentiation of human cardiomyocyte progenitor cells (CMPCs) by altering their membrane potential. We induced hyperpolarization in CMPCs by either co-culturing them with a K(ir)2.1-overexpressing cell line or by overnight culture in medium containing low potassium concentrations. Hyperpolarization led to increased intracellular calcium concentrations, activation of calcineurin signaling, increased cardiac specific gene and protein expression levels and, ultimately, to the formation of spontaneously beating cardiomyocytes. Thus, hyperpolarization is sufficient to induce differentiation of CMPCs, thereby revealing a novel mechanism for cardiomyogenic differentiation of heart-derived progenitor cells. PMID- 20354916 TI - In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery. AB - The objective of this study was to develop an ion-activated in situ gelling vehicle for ophthalmic delivery of matrine. The rheological properties of polymer solutions, including Gelrite, alginate, and Gelrite/alginate solution, were evaluated. In addition, the effect of formulation characteristics on in vitro release and in vivo precorneal drug kinetic of matrine was investigated. It was found that the optimum concentration of Gelrite solution for the in situ gel forming delivery systems was 0.3% (w/w) and that for alginate solution was 1.4% (w/w). The mixture of 0.2% Gelrite and 0.6% alginate solutions showed a significant enhancement in gel strength at physiological condition. On the basis of the in vitro results, the Gelrite formulations of matrine-containing alginate released the drug most slowly. For each tested polymer solution, the concentration of matrine in the precorneal area was higher than that of matrine containing simulated tear fluid (STF) almost at each time point (p < 0.05). The area under the curve of formulation 16 (0.2%Gelrite/0.6%alginate) was 4.65 times greater than that of containing matrine STF. Both the in vitro release and in vivo pharmacological studies indicated that the Gelrite/alginate solution had the better ability to retain drug than the Gelrite or alginate solutions alone. The tested formulation was found to be almost non-irritant in the ocular irritancy test. The overall results of this study revealed that the Gelrite/alginate mixture can be used as an in situ gelling vehicle to enhance ocular retention. PMID- 20354917 TI - Verapamil inhibits the glucose transport activity of GLUT1. AB - Calcium channel blocker toxicity has been associated with marked hyperglycemia responsive only to high-dose insulin therapy. The exact mechanism(s) of this induced hyperglycemia has not been clearly delineated. The glucose transporter GLUT1 is expressed in a wide variety of cell types and is largely responsible for a basal level of glucose transport. GLUT1 also is activated by cell stress. The specific purpose of this study was to investigate the effects of the calcium channel blocker verapamil on the glucose uptake activity of GLUT1 in L929 fibroblasts cells. Dose-dependent effects of verapamil on glucose uptake were studied using L929 fibroblast cells with 2-deoxyglucose. Verapamil had a dose dependent inhibitory effect on both basal and stress-activated transport activity of GLUT1. Basal activity was inhibited 50% by 300 MUM verapamil, while 150 MUM verapamil completely inhibited the activation induced by the stress of glucose deprivation. These effects were reversible and required verapamil to be present during the stress. Alteration of calcium concentrations by addition of 5 mM CaCl2 or 4 mM EDTA had no effect on verapamil action. This study reveals the unique finding that verapamil has inhibitory effects on the transport activity of GLUT1 independent of its effects on calcium concentrations. The inhibition of GLUT1 may be one of the contributing factors to the hyperglycemia observed in CCB poisoning. PMID- 20354918 TI - Intravenous lipid emulsion does not augment blood pressure recovery in a rabbit model of metoprolol toxicity. AB - Intravenous lipid emulsion (ILE) has been demonstrated to be an effective treatment for systemic toxicity associated with local anaesthetics and increasingly non-local anaesthetic agents of high lipophilicity. Effect for ILE has been demonstrated in animal models of propranolol poisoning; however, any benefit for ILE in more hydrophilic beta-blockers remains uncertain. We determined to examine the effect of ILE on haemodynamic recovery following induction of hypotension with the relatively hydrophilic beta-blocker, metoprolol. Twenty sedated, invasively monitored and mechanically ventilated adult New Zealand white rabbits underwent metoprolol infusion to mean arterial pressure (MAP) 60% baseline. Intravenous rescue was given according to the following groups: 6 mL/kg 20% lipid emulsion or 6 mL/kg 0.9% saline solution over 4 min. Haemodynamic parameters were obtained in 15 min. MAP was 70 (interquartile range (IQR), 58-82) mmHg saline group and 79 (IQR, 72-89) mmHg ILE group at baseline, and 38 (IQR, 33-40) mmHg saline group and 41 (IQR, 40-43) mmHg ILE group, respectively, following metoprolol infusion. No statistically significant difference between ILE and saline-treated groups was observed in MAP, or pulse rate, at any time point following rescue therapy. ILE was not effective in reversal of metoprolol-induced hypotension in this rabbit model. These findings lend inferential support for the 'lipid sink' as principal mechanism for the beneficial effect observed with ILE administration in other models of lipophilic beta-blocker-induced toxicity. PMID- 20354919 TI - 2007 survey of medical toxicology practice. AB - To date, there appear to be no studies investigating the practice settings of all Medical Toxicology (MT) diplomates. The MT Assessment of Practice Performance Taskforce queried all MT diplomates about their current practice settings relative to the number of patients seen, the most common diagnoses, and the percent of time spent in their roles as medical toxicologists (MTs) and in their primary specialty. One hundred twenty-seven surveys were completed (44% response rate). Seventy-nine percent of respondents were affiliated with poison centers. Eighty-eight percent of participants were clinically active and reported seeing or consulting on behalf of at least ten patients over a 2-year period. Acetaminophen toxicity was the most common diagnosis encountered by respondents. Other common diagnoses included antidepressant toxicity, antipsychotic toxicity, mental status alteration, metal/environmental toxicity, envenomation, and pesticide toxicity. While respondents were likely to spend more time in direct patient care in their primary specialty, compared to consulting on behalf of patients, they were more likely to consult on behalf of patients in their role as MTs. Respondents spent more time in research, education, and population health in their role as an MT than in their primary specialty. Administrative activities were more commonly reported in association with the respondents' primary specialty than in their role as MTs. Most MTs encounter certain diagnoses with significant frequency and see a substantial number of patients within these categories. The majority spends more time on direct patient care in their primary specialty but is actively engaged in MT education, research, population health, and administration. A longitudinal assessment of MT practice patterns could inform MT curricular development and practice performance evaluation. PMID- 20354921 TI - Plasma sex hormone-binding globulin, corticosteroid-binding globulin, cortisol, and free cortisol levels in outpatients attending a lipid disorders clinic: a cross-sectional study of 1137 subjects. AB - We measured plasma sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and total cortisol, and calculated free plasma cortisol in 1 137 subjects attending a hospital outpatient lipid disorders clinic to investigate whether or not these analytes correlated with the degree of insulin resistance and the presence of the metabolic syndrome. In both males and females, plasma SHBG correlated inversely with anthropometric measures and with fasting glucose, insulin, insulin resistance, and triglycerides, and positively with HDL cholesterol. However, in males with the metabolic syndrome, unlike females, the relationship between SHBG, some anthropometric measures, fasting glucose, insulin, and HDL-cholesterol were lost, which suggests that in males SHBG may not co-cluster with other components of the metabolic syndrome. In males and males with the metabolic syndrome, total plasma cortisol and calculated plasma free cortisol correlated positively with fasting glucose. Corticosteroid-binding globulin correlated inversely with percentage body fat and positively with HDL cholesterol in males with and without the metabolic syndrome. CBG correlated negatively with age in both sexes. Overall, the results confirm the finding that SHBG is a marker of insulin resistance in males and females and that SHBG is associated with fasting triglycerides in males with the metabolic syndrome. Importantly, SHBG could be considered a stronger component of the metabolic syndrome in females than in males. However, the aetiological role of CBG and cortisol in insulin resistance is uncertain, although in males, cortisol and CBG could be subtly related to the degree of insulin resistance. PMID- 20354920 TI - American College of Medical Toxicology position statement on post-chelator challenge urinary metal testing. PMID- 20354922 TI - Evolving concepts and controversies in lung transplantation. PMID- 20354923 TI - Candidate selection, overall results, and choosing the right operation. AB - Lung transplantation offers potential improvement in survival and improved quality of life in patients with end-stage lung disease. International guidelines for candidate selection have been agreed upon to aid physicians and providers in selecting appropriate candidates for lung transplantation. In recent years the U.S. lung allocation score (LAS) has been developed and implemented in an attempt to both maximize utility of scarce donor organs and provide benefit to those in need of lung transplantation. This has helped in the process of offering transplantation to those with the greatest need and best chance of survival. Appropriate lung transplantation candidates should have life-threatening lung disease but remain otherwise healthy, because significant comorbidities may increase the risk of poor outcomes after transplantation limiting long-term survival. Improved outcomes are seen through early referrals to a specialized center and vigilant evaluation to select the most appropriate candidates for lung transplantation. PMID- 20354924 TI - The impact of the lung allocation score. AB - The lung allocation score (LAS) was developed in an effort to facilitate lung transplantation to more urgent and ill patients, to decrease wait time, and to change the allocation process to a more merit-based system. Four years after the implementation of the LAS, we now evaluate the impact and outcomes of this system. We have found that registrations on the wait list as well as wait time have decreased. Mortality on the wait list has decreased. There has been significant change in the distribution of diagnoses receiving transplantation with no significant difference in survival in most areas. Patients with higher LAS scores have increased short-term mortality. The LAS has affected the allocation process as well as significant outcomes in the transplant patient population. PMID- 20354925 TI - Lung transplantation for chronic obstructive pulmonary disease: special considerations. AB - Since the introduction of lung transplantation nearly half a century ago, more procedures have been performed for chronic obstructive pulmonary disease (COPD) than for any other single indication. Because COPD tends to progress slowly and long-term survival is possible even in the advanced stages, the time at which transplantation should be offered remains unclear. Current recommendations rely on use of the BODE index to provide guidance on listing. Although both single lung transplantation (SLT) and bilateral lung transplantation (BLT) are suitable procedures for the COPD population, BLT has become the preferred procedure, particularly for patients under age 60, for whom it appears to offer superior survival and functional benefits. Whether lung transplantation truly extends survival for patients with COPD is uncertain. Preliminary answers have come from use of survivorship models that suggest a subset of COPD patients do derive a survival benefit, and that the size of this subgroup can be enhanced by selecting patients with extremely severe airflow obstruction and preferentially utilizing BLT. Those undergoing SLT are uniquely at risk for complications related to the remaining native lung-bronchogenic carcinoma and progressive hyperinflation-which are fortunately rare. PMID- 20354926 TI - Lung transplantation for advanced bronchiectasis. AB - Lung transplant (LT) can be successfully performed on patients with advanced bronchiectatic lung disease with subsequent good posttransplant quality of life and long-term outcome. Most of the data are derived from patients with cystic fibrosis (CF), but LT can be effective in patients with non-CF bronchiectasis as well. Despite the presence of chronic lower respiratory tract infection with bacterial pathogens in these patients pretransplant, posttransplant infections do not generally have significant impact on survival, although infection with antibiotic-resistant bacteria may complicate posttransplant management. Although benefit of LT for young children with CF is somewhat controversial, LT can clearly benefit older children and adults with advanced lung disease due to bronchiectasis. This article reviews indications (and contraindications) for LT, discusses particular problems that may arise posttransplant, and provides a rationale for referring patients with bronchiectasis for LT. PMID- 20354927 TI - Interstitial lung disease and lung transplantation. AB - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and carries the worst prognosis. Currently the best treatment option is lung transplantation. Historically patients with IPF had poor outcomes following referral for lung transplant due to high waiting-list mortality. The introduction of the lung allocation score in the United States in 2005 has reduced 1 year waiting-list mortality from 21% to 11% and also led to IPF becoming the most common diagnosis for lung transplantation. Although prioritizing all patients with IPF on the waiting list has led to a dramatic decline in waiting-list mortality, further improvements may be made by prioritizing which patients with IPF should be transplanted, with an emphasis on 6-minute walk testing, biomarkers, and the presence of pulmonary hypertension rather than traditional pulmonary function tests. The choice of surgical procedure and the prediction and management of posttransplant complications may also influence long-term outcomes. PMID- 20354928 TI - Pulmonary arterial hypertension and lung transplantation. AB - Heart-lung transplantation (HLT) and lung transplantation (LT) remain important therapies for idiopathic pulmonary arterial hypertension (IPAH), but recent advances in medical therapy can substantially delay or even obviate the need for transplantation, especially in certain PAH populations. By the early 1990s, the advent of epoprostenol, initially introduced as a bridge therapy to transplantation, in fact resulted in a survival advantage for IPAH. These benefits were comparable to those of HLT, and many patients who were thought to be destined for HLT were subsequently removed from active listing. Since 2005, however, the impact of the new lung allocation score (LAS) on IPAH has increased waiting list mortality. In the new millennium, the balance between the role of available medical therapies for PAH, the existing issues of the current LAS regarding the PAH patient, and the inherent morbidity associated with transplantation of PAH, will be critical to optimizing patient outcomes. The following discussion mainly focuses on adult IPAH, with some reference to congenital heart disease (CHD) and secondary PAH. PMID- 20354929 TI - Primary graft dysfunction: definition, risk factors, short- and long-term outcomes. AB - Primary graft dysfunction (PGD) is a form of early lung graft dysfunction that is a major cause of early morbidity and mortality following lung transplantation. Survivors of PGD have decreased long-term lung function and an increased risk of developing bronchiolitis obliterans syndrome (BOS), a manifestation of chronic graft dysfunction. This article reviews the current definition, contributing factors, and guidelines for grading clinical PGD, as well as controversies surrounding them. The current literature examining clinical risk factors for PGD is summarized, as are studies exploring molecular and biochemical markers for PGD prediction and severity. Studies examining the short- and long-term effects of PGD on lung transplant outcomes are reviewed. Lastly, we highlight the emerging concepts in lung transplantation that will potentially impact PGD incidence and outcomes. PMID- 20354930 TI - Current trends in immunosuppression for lung transplantation. AB - Lung transplant has become an established therapy in the treatment of end-stage lung disease. Many of the advances in the modern immunosuppression regimen have provided more quality and quantity of life to transplant patients. Immunosuppression agents target various aspects of the immune system to maximize graft tolerance while minimizing medication toxicities and side effects. Lung transplant regimens follow typical protocols but are always tailored to the individual patient based upon previous and current medical problems. Despite the various advances, acute and chronic rejections still occur in the majority of all lung transplants. For these reasons, long-term lung transplantation success remains a challenge. Further improvement in immunosuppression will be geared toward minimizing rejection and infection as well as being tailored to the individual patient. This review details the current armamentarium of immunosuppression medications and the current body of evidence supporting the current trends of usage. PMID- 20354931 TI - Acute cellular rejection and humoral sensitization in lung transplant recipients. AB - Despite the recent development of many new immunosuppressive agents for use in transplantation, acute cellular and humoral rejection represent extremely prevalent and serious complications after lung transplantation. Acute cellular rejection, defined as perivascular or bronchiolar mononuclear inflammation, affects over 50% of lung transplant recipients within the first year. Furthermore, the frequency and severity of acute rejections are the most important risk factors for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that severely limits survival after lung transplantation. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Emerging evidence also suggests that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens and is associated with an increased risk for BOS. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. Herein, we review the clinical presentation, diagnosis, mechanisms, and treatment of cellular and humoral rejection after lung transplantation. PMID- 20354932 TI - Chronic allograft rejection: epidemiology, diagnosis, pathogenesis, and treatment. AB - Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft rejection, in the form of obliterative bronchiolitis and its clinical correlate bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. The airway obstruction involved is classically progressive and unresponsive to treatment; however, the course is highly variable, and distinguishable phenotypes may exist. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome. PMID- 20354933 TI - Bronchoscopic monitoring after lung transplantation. AB - Despite advances in gene and immunological monitoring techniques that hold great promise for the future, fiberoptic bronchoscopy remains the gold standard to establish the presence or absence of acute pulmonary allograft rejection or infection after lung transplantation (LT). There is general agreement that clinically mandated transbronchial lung biopsies enhance diagnostic precision and have a satisfactory risk:benefit ratio in experienced hands. Surveillance transbronchial biopsies have a lower yield but may provide longitudinal insight into immunological events in the allograft, which can assist long-term management. Indeed, much of our knowledge about the significance of allograft histopathological events over time has been garnered from centers that perform routine surveillance procedures, and it is exactly the balance between individual and community benefit which underscores discussion about the value of invasive monitoring. Obliterative bronchiolitis (OB) is the most common cause of late chronic allograft dysfunction leading to death after LT. Significant OB is invariably associated with reduced graft function, denoted physiologically by the bronchiolitis obliterans syndrome (BOS). Importantly, not all BOS is due to OB; hence the move to develop an all embracing phraseology for late graft dysfunction, specifically "chronic lung allograft dysfunction" (CLAD). The major risk factor for BOS was once thought to be acute cellular rejection (ACR), but new data support an important role for lymphocytic bronchiolitis (LB) independent of so-called vascular acute rejection, albeit when diagnosed and treated. This review examines the role of fiberoptic bronchoscopy after LT as a surveillance tool versus a clinically mandated diagnostic procedure. PMID- 20354934 TI - Fungi and molds following lung transplantation. AB - The landscape of fungal infections in lung transplant recipients has significantly changed over the course of time. The initial predominance of CANDIDA species has given way to the prominence of ASPERGILLUS species in the current era followed by other mold infections, namely, SCEDOSPORIUM and Zygomycetes, which are emerging as newer pathogens. CRYPTOCOCCUS NEOFORMANS is another important pathogen responsible for the morbidity in lung transplant recipients. The use of widespread antifungal prophylaxis directed against the mold infections has resulted in delayed onset of invasive aspergillosis in lung transplant recipients. In recent studies cumulative incidence rate of invasive aspergillosis was noted to be 2.4% at 12 months. Invasive mold infections in lung transplant may present as tracheobronchitis, invasive pulmonary infections, or disseminated disease. Invasive pulmonary infections are now the most common manifestations of mold infections, followed by tracheobronchitis. Pre- or posttransplant ASPERGILLUS colonization, along with preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplants are considered significant risk factors for invasive aspergillosis. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. The appropriate antimold prophylaxis strategy, by the use of either voriconazole or inhaled amphotericin, remains to be fully determined. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in significant decreases in mortality. The risk factors for other mold infections such as SCEDOSPORIUM or Zygomycetes are being elucidated. Infections with these organisms, however, carry mortality up to 80%. The current article reviews the changes in the epidemiology of invasive molds and CRYPTOCOCCUS infections and other emerging fungal pathogens and highlights the controversies surrounding antifungal prophylaxis in lung transplant recipients. PMID- 20354935 TI - Complex bacterial infections pre- and posttransplant. AB - Infections complications following lung transplantation are associated with significant morbidity and mortality. Management of infections is most challenging in patients with cystic fibrosis (CF), but all lung transplant recipients are at heightened risk for opportunistic infections. Particularly in CF, pretransplant infections with PSEUDOMONAS AERUGINOSA, other highly resistant bacteria (e.g., STENOTROPHOMONAS, BURKHOLDERIA), and mycobacteria play a major role in recipient selection and post-lung transplant outcomes. Understanding the clinical impact and management strategies for each of these different pathogens is critical to maximizing the benefit of lung transplantation. In the review, we discuss each of these infections both as pretransplant risk factors as well as posttransplant pathogens and the individual issues that arise with each infection. PMID- 20354937 TI - Peroral endoscopic myotomy (POEM) for esophageal achalasia. AB - BACKGROUND: Peroral endoscopic myotomy (POEM) was developed by our group to provide a less invasive permanent treatment for esophageal achalasia. PATIENTS AND METHODS: POEM was performed in 17 consecutive patients with achalasia (10 men, 7 women; mean age 41.4 years). A long submucosal tunnel was created (mean length 12.4 cm), followed by endoscopic myotomy of circular muscle bundles of a mean total length of 8.1 cm (6.1 cm in distal esophagus and 2.0 cm in cardia). Smooth passage of an endoscope through the gastroesophageal junction was confirmed at the end of the procedure. RESULTS: In all cases POEM significantly reduced the dysphagia symptom score (from mean 10 to 1.3; P = 0.0003) and the resting lower esophageal sphincter (LES) pressure (from mean 52.4 mmHg to 19.9 mmHg; P = 0.0001). No serious complications related to POEM were encountered. During follow-up (mean 5 months), additional treatment or medication was necessary in only one patient (case 17) who developed reflux esophagitis (Los Angeles classification B); this was well controlled with regular intake of protein pump inhibitors (PPIs). CONCLUSIONS: The short-term outcome of POEM for achalasia was excellent; further studies on long-term efficacy and on comparison of POEM with other interventional therapies are awaited. PMID- 20354936 TI - Viral infections in lung transplant recipients. AB - Viral infections, including beta-herpes viruses and community respiratory viruses, are frequent pathogens in lung transplant recipients. These pathogens have become increasingly recognized as having a significant role in long-term outcomes of lung transplantation, which has been limited by the frequent development of infections, and chronic allograft dysfunction. Community respiratory viruses, such as influenza and respiratory syncytial virus have been associated with both acute rejection and chronic allograft dysfunction, particularly if early treatment was not administered. beta-herpes viruses, particularly cytomegalovirus (CMV), have long been associated with increased mortality in lung transplant recipients, although the advent of effective antiviral strategies has led to improved morbidity and mortality. Because these pathogens have been associated with altered immune responses against the allograft, a better understanding of immunopathogenesis of viral infections may lead to a broader approach to limit the morbidity from these pathogens. PMID- 20354938 TI - Interobserver agreement and accuracy among international experts with probe-based confocal laser endomicroscopy in predicting colorectal neoplasia. AB - BACKGROUND AND STUDY AIMS: A recently developed probe-based, confocal laser endomicroscopy (pCLE) system provides images of surface colonic epithelium in vivo during any endoscopy. Our objective was to assess interobserver agreement, sensitivity, specificity, and overall accuracy in the diagnosis of neoplasia using pCLE. PATIENTS AND METHODS: 53 patients undergoing surveillance and screening colonoscopies were enrolled. A total of 75 lesions, were detected and all were inspected by pCLE prior to sampling or polypectomy. Intravenous fluorescein was used to optimize tissue contrast. Three pCLE users, blinded to histopathologic and endoscopic findings, reviewed the set of video sequences for crypt architecture, vessel architecture, and colorectal neoplasia diagnosis. Histopathologic diagnosis from the corresponding biopsies was the reference gold standard. RESULTS: Of the 75 colorectal lesions, 50 were neoplastic and 25 non neoplastic. Interobserver agreement was moderate to good for the classification of neoplasia (kappa 0.55, 78 % pairwise agreement), and moderate for vessel architecture (kappa 0.41, 67 % pairwise agreement) and crypt architecture (kappa 0.49, 69 % pairwise agreement). In distinguishing between neoplastic and non neoplastic lesions, sensitivity, specificity, and accuracy were 76 %, 72 % and 75 %, respectively. When videos of good or excellent quality only were considered, interobserver agreement for classification of neoplasia was higher (kappa 0.83, 92 % pairwise agreement), as were sensitivity (88 %), specificity (89 %), and accuracy (88 %). CONCLUSION: An international collaboration group had moderate to good interobserver agreement using a pCLE system to predict neoplasia, which is acceptable for this study. PMID- 20354939 TI - Endoscopic ultrasound-guided fine-needle aspiration and trucut biopsy in the diagnosis of gastric stromal tumors: a randomized crossover study. AB - BACKGROUND AND AIM: The diagnosis of gastrointestinal stromal tumors (GISTs) has important prognostic and therapeutic implications. The specific diagnosis of GIST has to be based on immunocytochemistry. This study aimed to prospectively compare in a crossover manner the accuracy of endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB) in the specific diagnosis of gastric GISTs. We hypothesized that EUS-TCB is superior to EUS-FNA in this respect. PATIENTS AND METHODS: Forty patients with gastric subepithelial tumors suspected on the basis of EUS of being a GIST underwent both EUS-FNA and EUS-TCB. The sequence in which the techniques were employed was randomly assigned to avoid bias. RESULTS: Forty tumors were sampled (mean number of passes: 2.1 +/- 0.9 with EUS-TNB and 1.9 +/- 0.8 with EUS-FNA; P = not significant, NS). Final diagnoses were: GIST (n = 27), carcinoma (n = 2), leiomyoma (n = 1), schwannoma (n = 1), and no diagnosis possible (n = 9). Device failure occurred in 6 patients with EUS-TCB. A cytohistological diagnosis of mesenchymal tumor (n = 29) and carcinoma (n = 2) was made in 70 % of cases by EUS FNA and in 60 % of cases by EUS-TCB ( P = NS). Among the samples that were adequate, immunohistochemistry could be performed in 74 % of EUS-FNA samples and in 91 % of EUS-TCB samples ( P = 0.025). When inadequate samples were included, the overall diagnostic accuracy of EUS-FNA was 52 % and that of EUS-TCB was 55 % ( P = NS). There were no complications. CONCLUSIONS: EUS-TCB is not superior to EUS-FNA in GISTs because of the high rate of technical failure of trucut. However, when an adequate sample is obtained with EUS-TCB, immunohistochemical phenotyping is almost always possible. EUS-TCB can be safely performed in this set of patients. PMID- 20354940 TI - Natural orifice transluminal endoscopic surgery gastrotomy closure in porcine explants with the Padlock-G clip using the Lock-It system. AB - BACKGROUND AND STUDY AIMS: The success of transgastric surgery depends on reliable, secure closure of the gastrotomy. Few tests of the integrity of these closures have been published. This study aimed to determine whether a gastrotomy suitable for a NOTES procedure can be closed safely and effectively from within the stomach using a novel endoscopically placed device, the Padlock-G with the Lock-It delivery system. METHODS: In a series of eight consecutive porcine gastric explants gastrotomy was performed in an ex vivo animal laboratory, the gastrotomy being closed with the Padlock-G followed by burst pressure testing after completion of the procedure. Gastrotomies were made in porcine explants. T tags were placed on either side of the gastrotomy, and, with the T-tags pulled into an endoscopic cap, the Padlock-G was deployed. Gastric transmural pressure gradients at bursting of these closures were measured during insufflation of the explanted stomachs with a high-pressure insufflator. RESULTS: The mean burst pressure of the gastrotomy closures was 68.0 mm Hg (range: 45 - 107 mm Hg). All of the stomachs ultimately ruptured at the closure sites, with the exception of the stomach that ruptured at the highest value (107 mm Hg), which ruptured at a site approximately 5 cm away from the closure site. All of the closures were accomplished in 30 minutes or less. CONCLUSIONS: The Padlock-G clip provides a secure gastric closure for natural-orifice surgery. PMID- 20354941 TI - Myotomy for esophageal achalasia - laparoscopic versus peroral endoscopic approach. PMID- 20354942 TI - Preventing colorectal cancer and cancer mortality with colonoscopy: what we know and what we don't know. PMID- 20354943 TI - Endoscopic ultrasonography-guided biopsy for submucosal tumors: needless needling? PMID- 20354944 TI - The endoloop-clips technique for closure of large iatrogenic colonic perforations. PMID- 20354946 TI - Intragastric balloons for obesity: sometimes "a water bomb waiting to explode". PMID- 20354949 TI - Inhibitory effect of acteoside isolated from Cistanche tubulosa on chemical mediator release and inflammatory cytokine production by RBL-2H3 and KU812 cells. AB - The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. In this study, we investigated the effect of acteoside extracted from CISTANCHE TUBULOSA (Schrenk) R. Wight on the basophilic cell-mediated allergic reaction. The effect of acteoside on beta hexosaminidase release and intracellular [Ca (2+)] I level from rat basophilic leukemia (RBL-2H3) cells was determined. Also, ELISA was used to determine the level of histamine, tumor necrosis factor (TNF)- alpha, and interleukin (IL)-4 on human basophilic (KU812) cells. The effect of acteoside on basophilic cell viability was determined using the 3-[4,5-dimethylthiazolyl]-2,5 diphenyltetrazolium bromide (MTT) assay. These results indicated that 0.1-10.0 ug/mL acteoside inhibits the release of beta-hexosaminidase and [Ca (2+)] I influx from IgE-mediated RBL-2H3 cells. Moreover, acteoside inhibited histamine release, TNF- alpha, and IL-4 production in a dose-dependent manner from calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) or compound 48/80 stimulated KU812 cells. Our findings provide evidence that acteoside inhibits basophilic cell-derived immediate-type and delayed-type allergic reactions. This is the first report describing antiallergic activity of acteoside extracted from CISTANCHE TUBULOSA on basophilic cells. PMID- 20354950 TI - High frequency plant regeneration from leaf derived callus of high Delta9 tetrahydrocannabinol yielding Cannabis sativa L. AB - An efficient in vitro propagation protocol for rapidly producing Cannabis sativa plantlets from young leaf tissue was developed. Using gas chromatography-flame ionization detection (GC-FID), high THC yielding elite female clone of a drug type CANNABIS variety (MX) was screened and its vegetatively propagated clones were used for micropropagation. Calli were induced from leaf explant on Murashige and Skoog medium supplemented with different concentrations (0.5, 1.0, 1.5, and 2.0 uM) of indole- 3-acetic acid (IAA), indole- 3- butyric acid (IBA), naphthalene acetic acid (NAA), and 2,4-dichlorophenoxy-acetic acid (2,4-D) in combination with 1.0 uM of thidiazuron (TDZ) for the production of callus. The optimum callus growth and maintenance was in 0.5 uM NAA plus 1.0 uM TDZ. The two month-old calli were subcultured to MS media containing different concentrations of cytokinins (BAP, KN, TDZ). The rate of shoot induction and proliferation was highest in 0.5 uM TDZ. Of the various auxins (IAA, IBA, and NAA) tested, regenerated shoots rooted best on half strength MS medium (1/2 - MS) supplemented with 2.5 uM IBA. The rooted plantlets were successfully established in soil and grown to maturity with no gross variations in morphology and cannabinoids content at a survival rate of 95 % in the indoor growroom. PMID- 20354953 TI - Doing death better. PMID- 20354954 TI - Osborne (J) waves in hypothermia. PMID- 20354951 TI - Chemical and biological differentiation of Cortex Phellodendri Chinensis and Cortex Phellodendri Amurensis. AB - The Chinese herbal drug Cortex Phellodendri is derived from two species of PHELLODENDRON, P. CHINENSIS Schneid. and P. AMURENSE Rupr. Traditionally, Cortex Phellodendri Chinensis (CPC) and Cortex Phellodendri Amurensis (CPA) are used interchangeably because they are believed to share the same clinical efficacy. Berberine has been believed to be the active ingredient of the herbs. However, recent studies have shown that the content of berberine is much higher in CPC than in CPA. Interestingly, the majority of researches deal with CPA, the one with lower content of berberine. These observations provoke us to reconsider the active ingredients of Cortex Phellodendri. In this study, two traditional usages (antidiarrheal and antibacterial) of Cortex Phellodendri were compared with the chemical analysis of the two herb species used in its formulation. The results suggest that berberine is one of the active ingredients responsible for the antidiarrheal and antibacterial activities of the herbs, but that other chemical ingredients are also involved in regulating the biological actions of the herbal drug. These chemical ingredients may have the same or the opposite effect as berberine. The effectiveness of the herbs is more likely to correlate to the content of total alkaloids rather than to the content of berberine. PMID- 20354955 TI - Computed tomography for coronary anatomy and perfusion-guiding therapy in a patient with an occluded left anterior descending coronary artery. PMID- 20354956 TI - Look at the valve- A case of aortic stenosis that isn't. PMID- 20354957 TI - An example of the clinical selectivity of regadenoson for the A2a adenosine receptor. PMID- 20354959 TI - Primary cardiac lymphoma presenting with cardiac tamponade. AB - Primary cardiac lymphoma (PCL) is rare and occurs more commonly in immunocompromised patients. It can present in various ways, and diagnosis is particularly challenging, especially for the unsuspecting physician. We report a case of PCL in an immunocompetent 55-year-old man who initially presented with pyrexia of unknown origin, chest pain, dyspnea, and few early clinical signs, but who was later found to have cardiac tamponade and a large cardiac mass on echocardiography and cardiovascular magnetic resonance. A high index of suspicion is needed to diagnose PCL, and echocardiogram remains an important diagnostic tool. PMID- 20354958 TI - ST segment elevation during adenosine pharmacological stress testing in a patient with coronary artery disease. PMID- 20354960 TI - Rectus hematoma- An under-recognized complication of transfemoral cardiac catheterization. AB - We present a case of rectus hematoma occurring in the setting of transfemoral cardiac catheterization. This is a potentially deadly complication that is under reported and under-diagnosed. The goal of this article is to present a case of rectus hematoma alongside a comprehensive review of the literature. PMID- 20354961 TI - Electrocardiographic criteria in tako-tsubo cardiomyopathy-is there added certainty in a diagnosis per exclusionem? AB - Tako-Tsubo cardiomypathy (TTC), also known as transient left ventricular apical ballooning syndrome, is a stress-induced cardiomyopathy that predominantly affects post-menopausal, elderly women during emotional or physical stress. Apical left ventricular dysfunction in the absence of significant coronary artery disease is the hallmark of this condition. Because the electrocardiogram (ECG) classically depicts precordial ST-segment elevations and cardiac biomarkers can often be raised, it can be a challenge to differentiate TTC from an acute myocardial infarction (AMI). Indeed, several recent studies have proposed ECG criteria to differentiate TTC from an AMI. We present a case series of consecutive patients in whom we had employed such ECG criteria but were unable to conclusively differentiate TTC from an AMI. In each case, TTC remained a diagnosis per exclusionem, where coronary angiography was necessary to rule out myocardial infarction. We review and discuss the commonly used ECG criteria and highlight the evolutionary ECG changes commonly noted with TTC to help better prepare clinicians when dealing with patients with similar clinical scenarios. PMID- 20354962 TI - The perils of government-controlled comparative effectiveness. PMID- 20354963 TI - Technology assessment is the key to healthcare reform. PMID- 20354964 TI - Cardiovascular workforce - the potential impact of healthcare reform. PMID- 20354965 TI - Reforming healthcare delivery-accountable cardiovascular care in a new era. PMID- 20354966 TI - Heart hospitals, medicare, and cross-subsidization. AB - BACKGROUND: Compared with heart hospitals (HHs), does Medicare provide better reimbursement to traditional hospitals (THs)? METHODS: Diagnosis Related Group (DRG)-specific data from Hospital Compare (www.hospitalcompare.hhs.gov) were used to compare Medicare reimbursement to hospitals in nine HH markets, representing 10% of the national HH market. RESULTS: On average, markets contained 1.2 HHs and 8.1 THs. Average market size for invasive cardiac services was $13+/-8.4 million, with HHs having 36.1% of the market share. Compared with HHs, THs received significantly better reimbursement for coronary artery bypass graft (CABG: $20,281+/-3,047 HH versus $23,958+/-4,562 TH; p=0.004), percutaneous coronary intervention (PCI: $11,230+/-742 HH versus $13,347+/-2,662 TH; p<0.001), heart valve replacement ($33,710+/-4,056 HH versus $39,819+/-6,356 TH; p=0.001), pacemaker implantation ($11,245+/-706 HH versus $13,212+/-2,043 TH; p<0.001), heart failure ($5,622+/-489 HH versus $6,482+/-1,010 TH; p<0.001), chronic obstructive pulmonary disease (COPD: $4,893+/-802 HH versus $5,641+/-841 TH; p=0.013), pneumonia ($5,708+/-763 HH versus $6,456+/-1,136 TH; p=0.012), and diabetes ($4,115+/-355 HH versus $4,963+/-812 TH; p<0.001). CONCLUSIONS: The excessive reimbursement granted to THs for non-cardiac services is likely to reflect a policy decision to assist these hospitals with their cross subsidization of other services. If Medicare is to cut reimbursement to TH for CABG, PCI, or other services, Medicare should be asked to pay more for the services (e.g. emergency room care) that it currently reimburses only indirectly through the process of cross-subsidization. PMID- 20354967 TI - Logistical barriers to career development in academic cardiovascular multimodality imaging-challenges for future mentors. AB - OBJECTIVES: To define the practical logistics involved in the training, maintenance of technical proficiency, credentialing, and board certification for academic multimodality cardiovascular imaging specialists. BACKGROUND: Trends in cardiovascular imaging reflect a new paradigm emphasizing expertise in all four major modalities. In order to become a faculty member responsible for educating fellows-in-training, academic imagers face a daunting process with a shortage of senior mentors. METHODS: Detailed information describing fellowship training, the aggregate monthly volume of publications, credentialing, continuing medical education requirements, and board certification were obtained for each subspecialty area of cardiovascular medicine from various online sources. RESULTS: Compared with other subspecialty areas of cardiovascular medicine, multimodality imaging requires more reading (44% more pages of publications), more continuing medical education hours (300-467% more), and additional board certification (three boards instead of one or two). CONCLUSIONS: Achieving competency in multimodality imaging is difficult and expensive in 2009, but still possible. To advance the career development of current academic faculty in this area, future emphasis should be on streamlining training, accreditation, and board certification requirements while focusing on research proving the value of integrated imaging in cardiovascular disease. PMID- 20354968 TI - Instrumental variable methods in comparative safety and effectiveness research. AB - Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-a-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial. PMID- 20354969 TI - Oscillating chemiluminescence systems: state of the art. AB - Oscillating chemiluminescence (CL) was reported for the first time about 30 years ago. Since then several systems based on addition of a chemiluminescent reagent to a known oscillator system or based on the light emitting features of one component of the oscillating system, have been described. This information, scattered in the scientific literature, is compiled in the present paper. Several oscillating CL systems, including those based on Belousov-Zhabotinskii and Orban oscillators, or horseradish peroxidase-catalyzed reactions, among others, are critically presented. The application of this type of oscillatory systems is also discussed, in analytical chemistry and for educational purposes. PMID- 20354970 TI - Fluorescence quenching studies of nitrated polycyclic aromatic hydrocarbons. AB - The analysis of nitrated polycyclic aromatic hydrocarbons (NPAHs) is of great importance because of the mutagenicity and possible carcinogenic activity of these compounds, which are distributed widely in the environment. Nitro substituents in aromatic compounds are known to quench fluorescence and NPAHs have no intrinsic fluorescence, but they can be determined using their quenching effects on other fluorophores. The quenching effects of several important NPAHs on 1,2,3,4- tetrahydro-1-naphthol,5,6,7,8-tetrahydro-1-naphthol,4-(2-hydroxy-4 sulfo-1-naphthylazo)-2-naphthalene carboxylic acid and 7-amino-4-methyl coumarin have been studied. The singlet emission of these fluorophores is efficiently quenched by all the NPAHs, the quenching following the Stern-Volmer relationship. Quenching constants and the limits of detection and linear ranges of the quenchers have been determined in each case: the limits of detection are ca 1 um. PMID- 20354971 TI - A "force buffer" protecting immunoglobulin titin. PMID- 20354972 TI - Reversible storage of lithium in silver-coated three-dimensional macroporous silicon. PMID- 20354973 TI - High-performance oxygen-permeable membranes with an asymmetric structure using Ba(0.95)La(0.05)FeO(3-delta) perovskite-type oxide. PMID- 20354974 TI - Arrays of ultracompliant electrochemical dry gel cells for stretchable electronics. PMID- 20354975 TI - Electrothermal polymer nanocomposite actuators. PMID- 20354976 TI - Inelastic electron tunneling spectroscopy study of thin gate dielectrics. AB - A broad range of materials is currently being studied for possible use as the insulating layer in next generation metal-oxide-semiconductor transistors. Inelastic electron tunneling spectroscopy (IETS) has become a powerful tool to characterize both the structural and electrical properties of the resulting device structures made from these materials. IETS can address issues related to reactions and intermixing at interfaces, as well as properties related to carrier mobility, such as phonon modes and charge traps, for structures that are difficult to characterize accurately by other techniques. PMID- 20354977 TI - Chemical nanosensors based on composite molecularly imprinted polymer particles and surface-enhanced Raman scattering. PMID- 20354978 TI - Reversible Diels-Alder chemistry as a modular polymeric color switch. PMID- 20354981 TI - Ynamides: versatile tools in organic synthesis. AB - Ynamides display an exceptionally fine balance between stability and reactivity. They also offer unique and multiple opportunities for the inclusion of nitrogen based functionalities into organic molecules, and are emerging as especially useful and versatile building blocks for organic synthesis. Recent breakthroughs in the preparation of these substrates have revitalized interest in nitrogen substituted alkynes, and the beginning of the 21st century has witnessed an ever increasing number of publications reporting the development of new reactions or synthetic sequences starting from ynamides. This Review highlights major developments in this area. PMID- 20354983 TI - JSPS Asian Core Program: Cutting-Edge Organic Chemistry in Asia and IUPAC strategic planning for a New East and Southeast Asian network for organic chemistry. PMID- 20354984 TI - New approaches to the total synthesis of the bryostatin antitumor macrolides. AB - In this Focus Review, we give an overview of various bryostatin total syntheses. We also discuss the synthesis of various bryostatin analogues and their biological activity. Work reviewed includes that of Masamune, Evans, Nishiyama and Yamamura, Hale and Manaviazar, Trost, Wender, Keck, Burke, Thomas, and Krische. Our coverage is primarily for the period 2001-2009, since detailed reviews already exist on bryostatin total synthesis work and biology up to this time. PMID- 20354992 TI - Co-operative formation of monolithic tungsten oxide-polybenzylene hybrids via polymerization of benzyl alcohol and study of the catalytic activity of the tungsten oxide nanoparticles. AB - Hard and brittle monolithic tungsten oxide-polybenzylene nanohybrids can be obtained in one step by reacting tungsten iso-propoxide with benzyl alcohol. In a first step, crystalline tungsten oxide W(18)O(49) nanowires with a diameter of about 1.5 nm form via ether elimination reaction. Subsequently, the large residue of the benzyl alcohol is transformed to dibenzyl ether, which then polymerizes to polybenzylene, incorporating the nanoparticles into the forming polymer. The catalytic effect of the tungsten oxide nanowires on the quantitative formation of polybenzylene is proven by reacting them in different concentrations and at varying temperatures either with benzyl alcohol or with dibenzyl ether. Complete polymerization of benzyl alcohol is achieved within just 30 min by using a particle-to-monomer molar ratio of 1:115 at 160 degrees C. Lower reaction temperatures (100-130 degrees C) or higher ratios (1:340 and 1:680) prolong the reaction time to several hours. Further studies show that the tungsten oxide nanoparticles are able to completely polymerize various other alcohols with an aryl methanol group. PMID- 20354993 TI - Quorum sensing in sourdough Lactobacillus plantarum DC400: induction of plantaricin A (PlnA) under co-cultivation with other lactic acid bacteria and effect of PlnA on bacterial and Caco-2 cells. AB - This work aimed at showing the effect of pheromone plantaricin A (PlnA) by Lactobacillus plantarum DC400 towards other sourdough lactic acid bacteria and the potential of PlnA to protect the function of the human intestinal barrier. Growth and survival of sourdough lactic acid bacteria were differently affected by co-cultivation with L. plantarum DC400. Compared to mono-cultures, Lactobacillus sanfranciscensis DPPMA174 and Pediococcus pentosaceus 2XA3 showed growth inhibition and decreased viability when co-cultured with L. plantarum DC400. L. sanfranciscensis DPPMA174 induced the highest synthesis of PlnA. Survival of strain DPPMA174 only slightly varied by comparing the addition of PlnA to the culture medium and the co-cultivation with L. plantarum DC400. Compared to mono-culture, the proteome of L. sanfranciscensis DPPMA174 grown in co-culture with L. plantarum DC400 showed the variation of expression of 58 proteins (47 over expressed and 11 repressed). Thirty-four of them were also over expressed or repressed during growth of DPPMA174 with PlnA. Fifty-one of the above 58 proteins were identified. They had a central role in stress response, amino acid, energy and nucleotide metabolisms, membrane transport, regulation of transcription, and cell redox homeostasis. PlnA markedly increased the viability of human Caco-2/TC7 cells and the transepithelial electrical resistance. PMID- 20354995 TI - Toward mechanistic elucidation of iron acquisition in barley: efficient synthesis of mugineic acids and their transport activities. AB - Iron acquisition of graminaceous plants is characterized by the synthesis and secretion of iron-chelating compounds, mugineic acids (MAs), and by a specific uptake system for MAs-iron(III) complexes. We identified a transporter, HvYS1 (Hordeum vulgare L. yellow stripe 1), that is highly specific for MAs-iron(III) in barley roots. In this article we outline the characterization of HvYS1, and our recent work on the practical syntheses of MAs and investigations into the molecular basis of the specific transport of their iron(III) complexes by HvYS1. 2'-Deoxymugineic acid (DMA) was synthesized in a good overall yield from commercially available Boc-l-allylglycine using a minimal number of short simple operations with minimal protecting groups and work-up/purification procedures. The same strategy was also successfully applied to beta-hydroxy-l-allylglycine, which was obtained by an allylic oxidation of l-allylglycine derivatives, to give MA and 2'-epi-MA efficiently. HvYS1 transported the iron(III) complexes of all three synthetic specimens with efficiency similar to that of a natural mugineic acid complex. With sufficient quantities of MAs in hand, we analyzed the function of HvYS1 and revealed by preparing chimeric transporters that the sixth outer membrane loop of the transporter plays a vital role in substrate specificity. PMID- 20354994 TI - Proteomic analysis identifies in vivo candidate matrix metalloproteinase-9 substrates in the left ventricle post-myocardial infarction. AB - Matrix metalloproteinase-9 (MMP-9) deletion has been shown to improve remodeling of the left ventricle post-myocardial infarction (MI), but the mechanisms to explain this improvement have not been fully elucidated. MMP-9 has a broad range of in vitro substrates, but relevant in vivo substrates are incompletely defined. Accordingly, we evaluated the infarct regions of wild-type (wt) and MMP-9 null (null) mice using a proteomic strategy. Wt and null groups showed similar infarct sizes (48+/-3 in wt and 45+/-3% in null), indicating that both groups received an equal injury stimulus. Left ventricle infarct tissue was homogenized and analyzed by 2-DE and MS. Of 31 spot intensity differences, the intensities of 9 spots were higher and 22 spots were lower in null mice compared to wt (all p<0.05). Several extracellular matrix proteins were identified in these spots by MS, including fibronectin, tenascin-C, thrombospondin-1, and laminin. Fibronectin was observed on the gels at a lower than expected molecular weight in the wt group, which suggested substrate cleavage, and the lower molecular weight spot was observed at lower intensity in the MMP-9 null group, which suggested cleavage by MMP-9. Immunoblotting confirmed the presence of fibronectin cleavage products in the wt samples and lower levels in the absence of MMP-9. In conclusion, examining infarct tissue from wt and MMP-9 null mice by proteomic analysis provides a powerful and unique method to identify in vivo candidate MMP substrates. PMID- 20354996 TI - Clinical significance and distinctiveness of purging disorder and binge eating disorder. AB - OBJECTIVE: In the DSM-IV, individuals with binge eating disorder (BED) and those with purging disorder (PD) receive a diagnosis of eating disorder not otherwise specified (EDNOS), suggesting no meaningful differences between clinical presentations. This article compares PD and BED on eating disorder severity and comorbid disorders. METHOD: Individuals with PD (n = 33), DSM-IV BED (n = 23 with BMI >30 kg/m(2) , and n = 18 with BMI between 18.5 and 26.5 kg/m(2) ), and noneating disorder controls (n = 35) completed SCID-I interviews and questionnaires. RESULTS: Eating disorder groups reported significantly greater depression, body dissatisfaction, and dietary restraint and more Axis I disorders compared with controls. Compared with both the obese and normal weight BED groups, PD reported significantly greater dietary restraint and body dissatisfaction. Compared with obese BED, PD reported lower prevalence of impulse control disorders. DISCUSSION: Findings support differentiating among EDNOS based on behavioral presentation in both research and future nosological schemes such as the DSM-V. PMID- 20354997 TI - Nocturnal enuresis in adolescents with anorexia nervosa: prevalence, potential causes, and pathophysiology. AB - OBJECTIVE: The aim of this study was to determine the prevalence and potential causes of secondary nocturnal enuresis (NE) in adolescents with anorexia nervosa (AN). METHOD: Adolescents with AN completed the Incontinence Symptom Index Pediatric (ISI-P), a self-report urinary incontinence survey. Those who had NE associated with the onset of AN on the ISI-P completed a comprehensive clinical and laboratory evaluation, including urinary flow measurements. RESULTS: The prevalence of NE in adolescents with AN was 17.0% (10 of 59). The overall frequency of day- and night-time urinary incontinence symptoms in adolescents with AN was 62.7%; urgency incontinence, 57.6%; stress incontinence, 32.2%; and insensate incontinence, 17.0%. Nine of the 10 adolescents with NE had secondary NE and confirmed that bedwetting ceased after weight restoration. DISCUSSION: Decreased functional bladder capacity and detrusor instability may contribute to the NE observed in this population. The high prevalence of NE in adolescents with AN warrants further study to determine the potential causative pathways. Clinicians who work with adolescents with AN should assess for this problem. PMID- 20354998 TI - SAR versus S(inc): What is the appropriate RF exposure metric in the range 1-10 GHz? Part II: Using complex human body models. AB - This is the second of the two articles that present modeling data and reasoned arguments for specifying the appropriate crossover frequency at which incident power flux density (S(inc)) replaces the peak 10 g averaged value of the specific energy absorption rate (SAR) as the designated basic restriction for protecting against radiofrequency electromagnetic heating effects in the 1-10 GHz range. In our first study, we compared the degree of correlation between these basic restrictions and the peak-induced tissue temperature rise (DeltaT) for a representative range of population/exposure scenarios using simple multi-planar models exposed to plane wave conditions. In this complementary study, complex heterogeneous head models for an adult and 12-year-old child were analyzed at 1, 3, 6, 8, and 10 GHz for a variety of exposure conditions. The complex models indicate that peak DeltaT is better correlated with peak 10 g SAR than S(inc) at 1 and 3 GHz and with S(inc) at 6-10 GHz, in contrast to the results from Part I. Considering the planar and complex body modeling results together, and given the equivocal indications of the two metrics in the 6-10 GHz range, we recommend that the breakpoint be set at 6 GHz. This choice is also based on other considerations such as ease of assessment. We also recommend that the limit level of S(inc) should be adjusted to provide a better match with 10 g SAR in the induced tissue temperature rise. PMID- 20354999 TI - Comments on Kheifets et al. "Extremely low frequency electric fields and cancer: Assessing the evidence". PMID- 20355000 TI - Impact of pinna compression on the RF absorption in the heads of adult and juvenile cell phone users. AB - The electromagnetic exposure of cell phone users depends on several parameters. One of the most dominant of these is the distance between the cell phone and the head tissue. The pinna can be regarded as a spacer between the top of the phone and the head tissue. The size of this spacer has not yet been systematically studied. The objective of this article is to investigate the variations of distance as a function of age of the exposed person, and the mechanical force on the pinna and how it affects the peak spatial specific absorption rate (psSAR). The distances were measured for adults and children (6-8 years of age) while applying a well-defined force on the pinna using a custom-developed measurement device. The average distances of the pinnae to the heads and their standard deviations showed no major differences between the two age groups: 10.5 +/- 2.0 mm for children (6-8 years) and 9.5 +/- 2.0 mm for adults. The pinnae of our anatomical high-resolution head models of one adult and two children were transformed according to the measurement results. The numerical exposure analysis showed that the reduced distance due to the pinna compression can increase the maximum 10 g psSAR by approximately 2 dB for adults and children, if the exposure maximum is associated with the upper part of the phone. PMID- 20355003 TI - Polyneuropathy in type 1 and type 2 diabetes: do we need different examinations? PMID- 20355006 TI - Effects of lutein and zeaxanthin on aspects of eye health. AB - Lutein and zeaxanthin are members of the oxygenated carotenoids found particularly in egg yolks and dark-green leafy vegetables. A great deal of research has focused on their beneficial roles in eye health. The present article summarises the current literature related to the bioactivity of these carotenoids, emphasising their effects and possible mechanisms of action in relation to human eye health. Available evidence demonstrates that lutein and zeaxanthin are widely distributed in a number of body tissues and are uniquely concentrated in the retina and lens, indicating that each has a possible specific function in these two vital ocular tissues. Most of epidemiological studies and clinical trials support the notion that lutein and zeaxanthin have a potential role in the prevention and treatment of certain eye diseases such as age-related macular degeneration, cataract and retinitis pigmentosa. The biological mechanisms for the protective effects of these carotenoids may include powerful blue-light filtering activities and antioxidant properties. Although most studies point towards significant health benefits from lutein and zeaxanthin, further large-scale randomised supplementation trials are needed to define their effects on ocular function in health and disease. PMID- 20355007 TI - Characteristics and oil absorption in deep-fat fried batter prepared from ball milled wheat flour. AB - BACKGROUND: The porous structure generated during frying influences oil absorption and textural qualities. The alteration in physical properties of wheat flour is suspected to affect the structure formation. The present study investigated the effect of physicochemical changes in wheat flour by the ball milling process on structure formation and consequently oil absorption of a fried wheat flour batter model. RESULTS: Batter models containing 600 g kg(-1) moisture were made of 0-10 h ball-milled wheat flour and then fried in frying oil at 150 degrees C for 1-7 min. The samples made of milled flour possess larger pores and exhibit lower oil absorption than sample made of 0 h milled flour. The fracture force of a fried sample prepared from 5 and 10 h milled flour is lower than that of a sample prepared from 0 h milled flour. CONCLUSION: The decrease in glass transition temperature (T(g)) and melting temperature (T(m)) of milled flour affect the microstructure formation in the fried wheat flour batter. The microstructure is responsible for oil absorption and fracturability in fried food. The samples made of flour of longer ball-milling time have lower oil absorption and higher crispness. Ball-milling may be a tool to produce mechanically modified wheat flour which can reduce oil absorption for fried batter. PMID- 20355008 TI - Comparison of radiation-induced hydrocarbons for the identification of irradiated perilla and sesame seeds of different origins. AB - BACKGROUND: Perilla and sesame seeds, a rich source of energy, are commonly utilized in different forms in many countries. During the post-harvest period, they are contaminated with insects as well as microbes that may have importance for keeping quality and quarantine, and thus they can be treated with ionizing radiation for insect disinfestation and microbial decontamination. Reliable and routine methods to identify whether or not a food has been irradiated are needed to help consumers' understanding of irradiated food and promote international trade. In the present study, fat-derived hydrocarbons from irradiated perilla seeds and sesame seeds of Korean and Chinese origin were analyzed in order to identify irradiation treatment by comparing their properties during the post irradiation period. RESULTS: Gas chromatographic-mass spectrometric analysis showed that several saturated hydrocarbons, such as tetradecane, pentadecane, hexadecane and heptadecane, were found in the non-irradiated control samples, while four radiation-induced unsaturated hydrocarbons (R(2) = 0.647-0.997), such as 1,7,10-hexadecatriene (C(16:3)), 1,7-hexadecadiene (C(16:2)), 6,9 heptadecadiene (C(17:2)) and 8-heptadecene (C(17:1)), were detected in all irradiated samples at 0.5 kGy or higher, with variations according to sample and origin. Concentrations of all hydrocarbons were reduced during storage and could not be detected in 0.5 kGy irradiated Chinese sample of either seed after 8 months. CONCLUSION: Radiation-induced hydrocarbons (C(16:3, 16:2, 17:2, 17:1)) could be used as markers to identify irradiated perilla and sesame seeds of both Korean and Chinese origin at 1 kGy or higher for 8 months' storage at room temperature. PMID- 20355009 TI - Characterisation of proteolysis profile of Argentinean sheep cheeses made by two different production methods. AB - BACKGROUND: In this work the proteolysis profiles of Argentinean sheep cheeses made by two different production methods were studied in order to develop products with typical and defined features. Cheeses with a starter of Streptococcus thermophilus, curd cut to corn grain size, washed and heated to 43 degrees C (S cheeses) and cheeses with a mixed starter of Streptococcus thermophilus, Lactobacillus helveticus and Lactobacillus bulgaricus, curd cut to rice grain size, unwashed and heated to 47 degrees C (L cheeses) were manufactured. The cheeses were ripened at 12 degrees C and 80% relative humidity for 180 days and samples were taken throughout this period. RESULTS: Gross composition and primary proteolysis were similar for both types of cheeses. Streptococci counts diminished from 10(9) to 10(7) colony-forming units g(-1) during ripening in both S and L cheeses. Lactobacilli counts in L cheeses decreased during ripening and disappeared at 180 days. L cheeses had significantly lower pH values and showed higher peptidolysis than S cheeses. Triangle sensory evaluation indicated important differences between the two types of cheeses. CONCLUSION: S cheeses had a low proteolysis level and a soft flavour, making them appropriate for consumption after a short ripening time. L cheeses had a higher proteolysis level and more intense sensory characteristics, making them appropriate for consumption after a longer ripening time. PMID- 20355010 TI - Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome. AB - BACKGROUND: Andrographis paniculata is a health food used extensively in Southeast Asia, India and China and contains the pharmacologically important phytochemical andrographolide. Although andrographolide has antihepatotoxic activity, its bioavailability from A. paniculata is restricted by its rapid clearance and high plasma protein binding. The aim of this study was to formulate a herbosome of andrographolide with a naturally occurring phospholipid in order to enhance the bioavailability and hepatoprotective activity of andrographolide in rats. RESULTS: Andrographolide herbosome equivalent to 25 and 50 mg kg(-1) andrographolide significantly protected the liver of rats, restoring hepatic enzyme activities with respect to carbon tetrachloride-treated animals (P < 0.05 and P < 0.01 respectively). The rat plasma concentration of andrographolide obtained from the complex equivalent to 25 mg kg(-1) andrographolide (C(max) = 9.64 microg mL(-1)) was higher than that obtained from 25 mg kg(-1) andrographolide (C(max) = 6.79 microg mL(-1)), and the complex maintained its effective plasma concentration for a longer period of time. CONCLUSION: The results proved that the andrographolide complex produced by this method has better bioavailability and hence improved hepatoprotective activity compared with andrographolide at the same dose. Andrographolide complexation is therefore helpful in solving the problem of rapid clearance and low elimination half-life associated with andrographolide from A. paniculata. PMID- 20355011 TI - Effects of cultivar and culture conditions on gamma-aminobutyric acid accumulation in germinated fava beans (Vicia faba L.). AB - BACKGROUND: High levels of gamma-aminobutyric acid (GABA) accumulate in plant tissues under various stresses. GABA accumulation is also influenced by cultivar. This aim of this study was to select the most promising cultivar of fava bean for GABA accumulation and to optimise the culture conditions for GABA production in germinated fava beans by response surface methodology based on central composite design (CCD). RESULTS: GABA content and glutamate decarboxylase activity in germinated seeds of cultivar S2 were significantly higher than those in other cultivars (P < 0.05). A significant negative correlation (r = -0.765, P < 0.05) between germination percentage and 1000-kernel weight was observed. There was a linear relationship between GABA content and sprout length (R(2) = 0.816). The regression model fitted to the experimental data of CCD was valid in predicting GABA production in germinated fava beans. Temperature and pH value of the culture solution had significant effects on GABA content in germinated fava beans. Under optimal culture conditions (33.6 degrees C, pH 3.19 and an air flow rate of 1.19 L min(-1)), GABA content reached up to 2.41 g kg(-1) dry weight, about 48 times that in raw seeds. CONCLUSION: Germinated fava bean is a good resource of GABA rich food. Both cultivar and culture conditions have significant effects on GABA production. PMID- 20355012 TI - Enzymatic synthesis of chitosan-gelatin antimicrobial copolymer and its characterisation. AB - BACKGROUND: Schiff bases can be formed by reaction between acylamino and the amino group with microbial transglutaminase (MTGase) as catalyst and used in protein crosslinking in the food industry. A novel chitosan-gelatin copolymer for coating meat products can be synthesised using MTGase as catalyst, with the characteristics of both chitosan and gelatin. The aim of the present study was to synthesise and characterise chitosan-gelatin antimicrobial copolymer. RESULTS: The yield of copolymer increased with increasing gelatin/chitosan ratio, while bacteriostasis of Staphylococcus aureus by the copolymer decreased, showing that its bacteriostatic ability depended on the amino group in chitosan. Under optimal synthesis conditions of 50 degrees C, pH 6 and 40 min reaction time the copolymer yield was 64.5% at a gelatin/chitosan ratio of 0.6. Bacteriostasis of S. aureus by 10 g kg(-1) copolymer solution was 70% of that by chitosan. CONCLUSION: A novel biological dressing frame material with excellent biocompatibility and antibacterial properties has been successfully prepared. The results of this study provide a background for further investigation of potential applications of chitosan-gelatin copolymer in the areas of agriculture and food. PMID- 20355013 TI - Bile salt deconjugation and cholesterol removal from media by Lactobacillus strains used as probiotics in chickens. AB - BACKGROUND: Bile salt deconjugation by Lactobacillus strains is often closely linked to bile tolerance and survival of the strains in the gut and lowering of cholesterol in the host. The present study investigated the deconjugation of bile salts and removal of cholesterol by 12 Lactobacillus strains in vitro. The 12 strains were previously isolated from the gastrointestinal tract of chickens. RESULTS: The 12 Lactobacillus strains could deconjugate sodium glycocholate (GCA, 16.87-100%) and sodium taurocholate (TCA, 1.69-57.43%) bile salts to varying degrees, with all strains except L. salivarius I 24 having a higher affinity for GCA. The 12 Lactobacillus strains also showed significant (P < 0.05) differences in their ability to remove cholesterol from the growth medium (26.74-85.41%). Significant (P < 0.05) correlations were observed between cholesterol removal and deconjugation of TCA (r = 0.83) among the L. reuteri strains (C1, C10 and C16) and between cholesterol removal and deconjugation of TCA (r = 0.38) and GCA (r = 0.70) among the L. brevis strains (I 12, I 23, I 25, I 211 and I 218). In contrast, although L. gallinarum I 16 and I 26 and L. panis C 17 showed high deconjugating activity, there was no correlation between cholesterol removal and deconjugation of bile salts in these strains. CONCLUSION: The results showed that the 12 Lactobacillus strains were able to deconjugate bile salts and remove cholesterol in vitro, but not all strains with high deconjugating activity removed cholesterol effectively. PMID- 20355014 TI - Characterisation of a haemagglutinin from Hokkaido red bean (Phaseolus vulgaris cv. Hokkaido red bean). AB - BACKGROUND: A haemagglutinin was purified from Japanese Hokkaido red beans (Phaseolus vulgaris cv. Hokkaido red bean) with a procedure that included three chromatographic media. RESULTS: Haemagglutinating activity was adsorbed on DEAE cellulose, Affi-gel blue gel and Mono S. The pure haemagglutinin was a homodimer and each subunit was around 30 kDa in molecular mass. The haemagglutinating activity of this agglutinin could not be inhibited by a variety of simple sugars at 200 mmol L(-1) concentration including alpha-L-fucose, D(+)-galactose, D(+) glucose, D(+)-glucosamine, D(-)galactosamine, galacturonic acid, (+)-lactose, D(+)-melibose, L(-)-mannose, D(+)-mannose, D-mannosamine, D(+)-raffinose, L rhamnose, (+)-xylose and galacturonic acid. The haemagglutinating activity was fully retained at pH 4-11 and at 0-80 degrees C, but was completely lost at extreme pH values (0-2 and 13-14) and at very high temperatures (90 degrees C and 100 degrees C). The haemagglutinin exhibited a weak mitogenic activity toward mouse splenocytes, a stronger anti-proliferative activity than Con A toward HepG2 (human hepatoma) cells and inhibited >80% of HIV-1 reverse transcriptase inhibitory activity at 3.3 micromol L(-1). It was devoid of anti-fungal activity. CONCLUSION: Hokkaido red bean haemagglutinin possesses a potent anti proliferative effect on HepG2 cells. PMID- 20355015 TI - Effect of inoculated corn silage enriched with sunflower oil on rumen fermentation and lipid metabolism in an artificial rumen (RUSITEC). AB - BACKGROUND: Some rumen isolates are able to produce conjugated linoleic acid (CLA) from linoleic acid (LA) in vitro. Effects of providing diets containing corn silage (CS) and lucerne hay to an artificial rumen (RUSITEC) in which the corn was not inoculated (CS), or inoculated with Lactobacillus plantarum CCM 4000 (CS + LP), Lactobacillus fermentum LF2 (CS + LF) or Enterococcus faecium CCM 4231 (CS + EF) and supplied with sunflower oil (SO; 30 g kg(-1); w/w) on rumen metabolism were examined. RESULTS: The SO affected the outputs of all fatty acids. TVA output of uninoculated CS with SO was lower as compared to inoculated CS. The interaction of the CS x SO in the daily output of TVA was detected (P < 0.001). The biohydrogenation of oleic, linoleic, alpha-linolenic and total fatty acids was influenced by SO (P < 0.05 and P < 0.001). CONCLUSION: Inoculated silage induces changes in the rumen metabolism which might be related to differences observed in the extent of rumen BH of PUFA in RUSITEC. SO supplementation might positively enhances the production of some rumen intermediates; however, relationships between inoculated silages and oil supplementation can be presumed in the daily production of trans-vaccenic acid. PMID- 20355016 TI - Tuber yield and quality characteristics of potatoes for off-season crops in a Mediterranean environment. AB - BACKGROUND: There is little research on evaluating the compatibility of potatoes for double cropping in southern Italy. The aim of this investigation was to assess tuber yield and some qualitative traits of tubers such as skin colour, tuber dry matter content and tuber nitrate content, both in winter-spring and in summer-autumn crops, as influenced by genotype and harvest time. RESULTS: Yield, skin colour and dry matter content of tubers were higher in the winter-spring crop than in the summer-autumn crop, attributable to the advantageous lag time in spring between solar radiation and temperatures and the disadvantageous lag in autumn. Spunta and Arinda performed well within each crop season, whereas Ninfa showed an important yield loss in autumn. In both off-season crops, delaying tuber harvest until leaf senescence increased yield and improved quality attributes such as tuber dry matter content and skin colour, whereas nitrate contents significantly decreased in the winter-spring crop and increased in the summer-autumn crop. Ninfa showed less tendency than Arinda and Spunta to accumulate nitrate in tubers in both off-season crops. CONCLUSION: It might be advantageous to examine in further research which mechanisms sustain compatibility to the autumn and assess other quality characteristics for the fresh market in the contrasting climatic conditions of the two off-season crops. PMID- 20355017 TI - Screening sweetcorn for enhanced zeaxanthin concentration. AB - BACKGROUND: New varieties of fruits and vegetables, with higher carotenoid levels, are being developed to improve the potential health benefits to consumers. To assist the development of a new variety of high zeaxanthin sweetcorn, an analytical screening method was developed, including chromameter measurement of hue angle and optimized extraction for HPLC, and applied to 385 lines of a breeding population and six commercial varieties. RESULTS: Saponification had no effect on carotenoid extraction. In the breeding population, carotenoid levels had a wide range with the highest levels of zeaxanthin being 11.9 mg kg(-1) fresh weight, which was at least six times greater than the tested commercial varieties. The regression of hue angle versus zeaxanthin was described by the equation, hue angle = 76.16 + 4.50 x exp(-0.24 x zeaxanthin) + 11.73 x exp(-0.24 x zeaxanthin), r(2) of 0.59. The top 6% of lines, with regards to zeaxanthin (zeaxanthin + beta-cryptoxanthin + beta-carotene) and total carotenoids, all had hue angles or= 0.9981), with limits of detection of 0.002, 0.2, 0.3 and 0.2 ng mL(-1) respectively. At a flow rate of 2 mL min(-1), complete determination of Sudan dyes, including sampling and washing, could be accomplished in 40 s, with relative standard deviations of less than 5% (n = 7). CONCLUSION: The proposed method was successfully applied to the determination of Sudan IV in contaminated hot chilli powder, with recoveries ranging from 89.3 to 108.4%. The possible mechanism of enhancement of the luminol/dissolved oxygen CL reaction by Sudan IV can be attributed to the acceleration of electron transfer. Compared with other procedures, the proposed CL method offers the highest sensitivity and the least reagent consumption for the determination of Sudan IV. PMID- 20355050 TI - Aqueous extract of Hibiscus sabdariffa L. decelerates acetaminophen-induced acute liver damage by reducing cell death and oxidative stress in mouse experimental models. AB - BACKGROUND: Acetaminophen (AAP)-induced oxidative stress can cause cell death to induce liver damage. The antioxidant effect of Hibiscus sabdariffa L. (HS) was shown in previous studies. In this study the effect of HS extract (HSE) on AAP induced liver injury in BALB/c mice was investigated. RESULTS: In vivo, BALB/c mice were fed orally with 200, 400 or 600 mg kg(-1) HSE for 2 weeks and then injected with 1000 mg kg(-1) AAP. Pretreatment with HSE decreased lipid peroxidation and increased catalase activity and glutathione level. It also decreased AAP-induced liver injury, accompanied by decreased expression of pJNK, Bax and tBid in the liver. Additionally, HSE protected BALB/c normal liver cells from AAP-induced damage in vitro. CONCLUSION: It has been demonstrated that HSE can protect the mouse liver from AAP-induced injury and that the protective mechanism might involve decreasing oxidative stress and reducing cell death. PMID- 20355052 TI - Effect of grass-clover forage and whole-wheat feeding on the sensory quality of eggs. AB - BACKGROUND: A sensory panel evaluated the sensory profile of eggs from hens from three experimental systems: (1) an indoor system x normal layer diet (InL), (2) a grass-clover forage system x normal layer diet (GrL), and (3) a grass-clover forage system x whole wheat and oyster shells (GrW). RESULTS: The taste of the albumen was significantly more 'watery' and the yolks a darker yellow/orange in the eggs from the GrL and GrW groups. The yolk was darkest from the GrW group. The yolks from the InL and GrW groups had a significantly more 'fresh', less 'animal', 'cardboard', and 'intense' aroma than the GrL group. The taste of the yolks from the InL and GrW groups was significantly more 'fresh' and less 'cardboard'-like compared to the GrL group. The yolks tasted significantly less 'sulfurous' in the GrW group than in the GrL group. CONCLUSION: The combination of a high feed intake from a grass-clover pasture and the type of feed allocated is an important factor in relation to the sensory quality of eggs. Thus, a less favourable sensory profile of eggs was found from hens on a grass-clover pasture and fed a normal layer diet. PMID- 20355053 TI - Protective effects of enzymatic digest from Ecklonia cava against high glucose induced oxidative stress in human umbilical vein endothelial cells. AB - BACKGROUND: Antioxidants can prevent pathological damage caused by hyperglycaemia induced oxidative stress associated with diabetes. In the present study, we investigated whether the brown alga Ecklonia cava has protective effects against high glucose-induced oxidative stress in Human umbilical vein endothelial cells (HUVECs). For that purpose, we prepared an enzymatic digest from E. cava (ECC) by using the carbohydrate, Celluclast. RESULTS: High glucose treatment induced HUVECs cell death, but ECC, at a concentration of 10 or 100 microg mL(-1), significantly inhibited the high glucose-induced cytotoxicity. Furthermore, treatment with ECC dose-dependently decreased thiobarbituric acid reactive substances (TBARS), intracellular generation of reactive oxygen species, and the nitric oxide level increased by high glucose. In addition, ECC treatment increased activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase in high-glucose pretreated HUVECs. High glucose levels induced the overexpression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-kappa B proteins in HUVECs, but ECC treatment reduced the overexpression of these proteins. CONCLUSION: These results suggest that ECC is a potential therapeutic agent that will reduce the damage caused by hyperglycaemia-induced oxidative stress associated with diabetes. PMID- 20355054 TI - Nitrate modifies the assimilation pattern of ammonium and urea in wheat seedlings. AB - BACKGROUND: In certain plant species, ammonium or urea nutrition can cause negative effects on plant development which can result in toxic symptoms. Some authors suggest that the presence of nitrate can alleviate these symptoms by increasing ammonium and urea assimilation, avoiding its accumulation. In order to study this hypothesis, wheat (Triticum aestivum L.) seedlings were grown with various nitrogen supplies containing the main nitrogen forms (ammonium, nitrate and urea). Amino acids content and the activity of the three main enzymes involved in nitrogen assimilation (nitrate reductase, glutamine synthetase and urease) were studied. RESULTS: The application of nitrate along with urea and/or ammonium was not associated with a time-sustained increase in the activity of glutamine synthetase and urease. Amino acid analysis revealed that nitrate induced changes in amino acid metabolism enhancing its concentration. Likewise the content of protein was also higher in nitrate-treated plants. CONCLUSION: These results suggest that the effect of nitrate is compatible with a rapid and transient increase in the activity of glutamine synthetase and urease during the first hour after the onset of treatments. Nevertheless, a possible effect of nitrate reducing ammonium accumulation through the activation of alternative metabolic pathways different from that involving glutamine synthetase cannot be ruled out. Finally, nitrate effects on amino acid concentration indicate that, whereas ammonium assimilation takes place principally in the root, urea and nitrate assimilation occurred in the shoot, under the conditions of the experiment. PMID- 20355055 TI - Participation of cysteine protease cathepsin L in the gel disintegration of red bulleye (Priacanthus macracanthus) surimi gel paste. AB - BACKGROUND: Endogenous proteases, among them cysteine-type proteases, are reported to contribute to gel disintegration, resulting in kamaboko of poor quality. Severe gel disintegration occurs in red bulleye surimi gel paste. The objective of this study was to clarify the participation of cysteine protease cathepsin L in the gel disintegration of red bulleye surimi. The surimi was made into kamaboko with and without cathepsin L inhibitors. To confirm its hydrolysis action, crude cathepsin L was also extracted and added to the surimi to make kamaboko. RESULTS: The gel strength of kamaboko obtained by both one-step (50 degrees C, 2 h) and two-step (50 degrees C, 2 h + 80 degrees C, 20 min) heating was very low in the absence of inhibitors. Protease inhibitors E-64 and leupeptin were found to enhance the gel strength considerably. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the hydrolysis of kamaboko was promoted by crude cathepsin L and inhibited by E-64 and leupeptin. The gel strength of two-step heated kamaboko was increased from 12 to 110 and 130 g cm( 2) by E-64 and leupeptin respectively at a concentration of 0.2 g kg(-1) surimi. CONCLUSION: Endogenous cathepsin L of red bulleye surimi participates in gel disintegration during kamaboko processing. It does so by degrading the myosin heavy chain of actomyosin and consequently hindering the gelation of red bulleye surimi. PMID- 20355056 TI - Cod and rainbow trout as freeze-chilled meal elements. AB - BACKGROUND: 'Meal elements' are elements of a meal, e.g. portions of pre-fried meat, sauces, frozen fish or pre-processed vegetables typically prepared industrially. The meal elements are distributed to professional satellite kitchens, where the staff can combine them into complete meals. Freeze-chilling is a process consisting of freezing and frozen storage followed by thawing and chilled storage. Combining the two would enable the manufacturer to produce large quantities of frozen meal elements to be released into the chill chain according to demand. We have studied the influence of freeze-chilling on the quality attributes of cod and rainbow trout portions. Sensory profiling and chemical analyses were used to determine the changes in quality after slow thawing and subsequent chill storage and to find the high-quality shelf life. RESULTS: Cod had a consistent and high sensory quality during the first 6 days of chilled storage, and the corresponding time for rainbow trout was 10 days. After this period the sensory quality decreased and chemical indicators of spoilage were seen to increase. CONCLUSION: The consistent quality during storage and the high quality shelf life are practically applicable and cod and rainbow trout seem potential candidates for freeze-chilled meal elements. PMID- 20355057 TI - Chemistry and antioxidant activity of essential oil and oleoresins of black caraway (Carum bulbocastanum) fruits: Part 69. AB - BACKGROUND: The present study describes the chemical analysis of the essential oil and oleoresins from caraway, which have been studied by using GC-MS. The paper also explains the importance of the extracted oil and oleoresins in the antioxidant activities of target plant species. RESULTS: GC-MS analysis of caraway essential oil showed 51 compounds representing about 96.6% of the total weight. The major components were dillapiole (44.6%), germacrene-beta (14.1%), nothoapiole (8.3%), and beta-selinene (6.8%), along with many other components in minor amounts. Major components in ethyl acetate and iso-octane oleoresins are dillapiole, nothoapiole and germacrene-beta, whereas in ethanol oleoresin contains dillapiole (25%), sitosterol (21.3%) stigmasterol (9.5%) and nothoapiole (8.1%). The antioxidant activity was evaluated by various antioxidant assays such as peroxide, thiobarbituric acid and p-anisidine values. These experiments were further supported by other complementary antioxidant assays such as ferric thiocyanate method in linoleic acid system, reducing power, and scavenging effects on 1,1'-diphenyl-2-picrylhydrazyl (DPPH). Both the caraway volatile oil and its oleoresins showed strong antioxidant activity in comparison with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). CONCLUSION: This study provides additional information about the chemistry and antioxidant activity of caraway. Hence, caraway may be used as natural food preservatives. PMID- 20355058 TI - Fatty acid and essential oil composition of three Tunisian caraway (Carum carvi L.) seed ecotypes. AB - BACKGROUND: The essential oil and fatty acid composition of Tunisian annual caraway (Carum carvi L.) seeds from three ecotypes was investigated by gas chromatography and gas chromatography-mass spectrometry analyses. RESULTS: Total fatty acid (TFA) proportion of caraway seeds varied from 2.95% to 5.68% (w/w). The fatty acid composition revealed that Tunisian caraway seed oil is rich in an unusual fatty acid-petroselinic acid-the proportion of which varied from 31.53% and 38.36% of TFA. Essential oil yields were relatively low and ranged from 0.86% to 1.20% (w/w). Forty-one volatile compounds were identified, the main ones being carvone (76.78-80.53%) and limonene (13.05-20.29%). CONCLUSION: Tunisian caraway seed oil is rich in an unusual fatty acid-petroselinic acid-which is of potential industrial significance. In addition, Tunisian caraway essential oil is carvone chemotype. This fact is of great economic interest due to the several applications of carvone in the alimentary and medicinal industries. PMID- 20355059 TI - In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark. AB - BACKGROUND: Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. RESULTS: Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. CONCLUSION: The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus. PMID- 20355060 TI - Development and in-house validation of the event-specific qualitative and quantitative PCR detection methods for genetically modified cotton MON15985. AB - BACKGROUND: To implement genetically modified organism (GMO) labeling regulations, an event-specific analysis method based on the junction sequence between exogenous integration and host genomic DNA has become the preferential approach for GMO identification and quantification. RESULTS: In this study, specific primers and TaqMan probes based on the revealed 5'-end junction sequence of GM cotton MON15985 were designed, and qualitative and quantitative polymerase chain reaction (PCR) assays were established employing the designed primers and probes. In the qualitative PCR assay, the limit of detection (LOD) was 0.5 g kg( 1) in 100 ng total cotton genomic DNA, corresponding to about 17 copies of haploid cotton genomic DNA, and the LOD and limit of quantification (LOQ) for quantitative PCR assay were 10 and 17 copies of haploid cotton genomic DNA, respectively. Furthermore, the developed quantitative PCR assays were validated in-house by five different researchers. Also, five practical samples with known GM contents were quantified using the developed PCR assay in in-house validation, and the bias between the true and quantification values ranged from 2.06% to 12.59%. CONCLUSION: This study shows that the developed qualitative and quantitative PCR methods are applicable for the identification and quantification of GM cotton MON15985 and its derivates. PMID- 20355061 TI - Effect of acetic acid deamidation-induced modification on functional and nutritional properties and conformation of wheat gluten. AB - BACKGROUND: Acids are often used for deamidating proteins, but the literature on acetic acid deamidation of proteins is sparse. Previous research on acetic acid induced modification of proteins has focused on peptide proteolysis by relatively high concentrations of acetic acid (>1.5 mol L(-1)) rather than on the accompanying effect of deamidation. Therefore the objective of this study was to determine the deamidation effect of acetic acid with as little peptide proteolysis as possible by employing low-concentration acetic acid (<0.05 mol L( 1)) to deamidate wheat gluten. Changes in surface hydrophobicity, conformation, functional properties and nutritional characteristics of acetic acid-modified samples were determined and compared with those of hydrochloric acid (HCl) modified samples. RESULTS: At similar degree of deamidation and nitrogen solubility index, samples deamidated with acetic acid showed less destruction of peptides bandings, better foaming properties and a more decompacted form (lower S -S content in protein as determined by Raman spectroscopy) than those deamidated with HCl and also exhibited improved emulsification capacity and emulsion stability compared with native wheat gluten. Acetic acid deamidation led to fewer changes in peptide molecular size and secondary structure of wheat gluten compared with HCl deamidation according to the results of sodium dodecyl sulfate polyacrylamide gel electrophoresis and Fourier transform infrared spectroscopy respectively. Amino acid analysis revealed that the nutritional characteristics of wheat gluten were well maintained after deamidation with acetic acid. CONCLUSION: The results show that low-concentration acetic acid can modify wheat gluten mainly by deamidation, resulting in deamidated wheat gluten with good functional and nutritional properties. PMID- 20355062 TI - Red clover (Trifolium pratense L.) isoflavones: root phenolic compounds affected by biotic and abiotic stress factors. AB - BACKGROUND: Phenolic compounds have recently received considerable attention for their ability to protect plant and human cells from oxidative stress-induced damage. Red clover (Trifolium pratense L.) is a rich source of isoflavonoids with multiple potential protective functions. The aim of this study was to identify and characterise phenolic compounds in red clover roots by high-performance liquid chromatography and mass spectrometry and to study the effects of stress factors and growth stage on root phenolics. RESULTS: A total of 28 phenolic compounds were tentatively identified in red clover roots. The most abundant phenolics in pot-grown roots were formononetin glycoside malonate (G-M) (1.51 4.26 mg g(-1)), formononetin (2.21-3.57 mg g(-1)) and biochanin A (1.73-2.17 mg g(-1)), whereas field-grown roots were rich in formononetin-G-M (3.90-4.27 mg g( 1)), maackiain-G-M (2.35-3.02 mg g(-1)) and pseudobaptigenin-G-M (1.80-2.58 mg g( 1)). Concentrations were affected by the growth stage. Ozone exposure slightly affected the total phenolic content in roots and also had minor effects on individual compounds. CONCLUSION: Elevated ozone, cultivation regime and growth stage affected the levels of phenolics in red clover roots, suggesting sensitivity of root phenolics to biotic and abiotic stress conditions. The high levels of phenolics found in roots even in late autumn may be utilised in many applications. PMID- 20355063 TI - Physicochemical properties of octenyl succinic anhydride-modified potato starch with different degrees of substitution. AB - BACKGROUND: Esterified starch is an important type of modified starch. In particular, octenyl succinic anhydride-modified starch (OSA starch) is widely used in the food industry. However, there has been little research on the properties of products with different degrees of substitution (DS). Therefore the aim of this study was to analyse the physicochemical properties of products with different DS. RESULTS: OSA starch samples with different DS were prepared from potato starch. Two new peaks were observed in the Fourier transform infrared spectrum, one at 1724 cm(-1) due to C==O and one at 1572 cm(-1) due to RCOO--. Emulsifying capacity and emulsion stability improved with increasing DS. Rheological analysis showed the occurrence of the 'shear-thinning' phenomenon, the viscosity of the sample with DS = 0.0211 being even lower than that of native starch. A decrease in syneresis rate from 88.3% (native starch) to 39.0% (DS = 0.0211) indicated that freeze-thaw stability was improved. CONCLUSION: The physicochemical properties of OSA potato starch were better than those of native potato starch. Freeze-thaw stability, emulsifying capacity and emulsion stability improved with increasing DS. Viscosity increased at lower DS but decreased at DS = 0.0211. PMID- 20355064 TI - The effect of dietary Laminaria-derived laminarin and fucoidan on nutrient digestibility, nitrogen utilisation, intestinal microflora and volatile fatty acid concentration in pigs. AB - BACKGROUND: In experiment 1, 30 boars were assigned to one of five treatments (n = 6): T1, 0 g kg(-1) seaweed extract (SWE); T2, 0.7 g kg(-1) SWE; T3, 1.4 g kg( 1) SWE; T4, 2.8 g kg(-1) SWE and T5, 5.6 g kg(-1) SWE. The extract contained laminarin and fucoidan only and was extracted from Laminaria spp. In experiment 2, 28 boars were assigned, in a 2 x 2 factorial to one of four treatments (n = 7): T1, control; T2, control plus 300 mg laminarin; T3, control plus 240 mg fucoidan; T4, control plus 300 mg laminarin and 240 mg fucoidan kg(-1) diet. RESULTS: In experiment 1 there was a response to SWE on colonic Bifidobacterium spp. (P < 0.01 quadratic), Enterobacterium spp. (quadratic P < 0.05) and on caecal Enterobacterium spp. (quadratic P < 0.05). In experiment 2 there was an interaction (P < 0.05) between laminarin and fucoidan supplementation on Enterobacterium spp. in the proximal and distal colon. Pigs offered laminarin had reduced Enterobacterium spp. compared with pigs offered the control diet. However, the combination of laminarin and fucoidan had increased Enterobacterium spp. compared with alone. Pigs offered diets containing fucoidan had increased Lactobacilli spp. in the proximal colon (P < 0.05) and distal colon (P < 0.001) compared with non-fucoidan diets. CONCLUSION: Overall, the reductions in intestinal Enterobacterium spp. and increases in Lactobacilli spp. obtained suggest that laminarin and fucoidan may provide a dietary means to improve gut health in pigs. PMID- 20355065 TI - Volatile compounds profile and sensory evaluation of Beninese condiments produced by inocula of Bacillus subtilis. AB - BACKGROUND: Three Beninese food condiments (ABS1(24h), IBS2(48h) and SBS3(48h)) were produced by controlled fermentation of African locust beans using inocula of pure cultures of Bacillus subtilis, BS1, BS2 and BS3, respectively. Quantitative and qualitative assessments of the volatile compounds in the condiments produced have been performed using the Likens-Nickerson simultaneous distillation extraction method and GC-MS analysis, followed by a sensory evaluation in comparison with the spontaneously fermented condiments. RESULTS: A total of 94 volatile compounds have been found including 53 compounds identified in relatively high concentrations and were subdivided into seven main groups with the predominance of four major groups: pyrazines, aldehydes, ketones and alcohols. Compared to the spontaneously fermented condiments, volatile compounds identified in controlled fermented condiments have been found in high number and in concentrations which varied according to the inoculum of B. subtilis used. The condiments produced with starter cultures scored significantly (P < 0.05) higher for odour than the spontaneously fermented condiments. But the overall acceptability (7/10) of the two types of condiments was similar. CONCLUSION: The investigated B. subtilis, BS1, BS2 and BS3 can be considered as potential starter cultures for the fermentation of African locust beans to produce good quality of Beninese food condiments. PMID- 20355066 TI - Composition, nutritional aspects and effect on serum parameters of marine algae Ulva rigida. AB - BACKGROUND: Algae are commonly consumed in Asia and have also gained popularity in Europe. However, data on the bioavailability of their components are limited. The present study was designed to determine the composition of Ulva rigida and the effects of inclusion of 10% of the algae in a standard diet for 4 weeks on nutritive value and serum parameters in order to consider the usefulness of Ulva as a dietary supplement. RESULTS: Ulva rigida is rich in protein, carbohydrates, fibre, vitamins and minerals and has a low lipid content. Analysis of the amino acid composition revealed good-quality protein. The algae were well accepted by experimental animals and did not significantly change nutritional parameters but reduced LDL cholesterol. CONCLUSIONS: Ulva rigida is an excellent source of nutrients and could improve a balanced diet. Further studies are required to research the potential of the seaweed as a natural source of bioactive compounds. PMID- 20355067 TI - Experimental evidence for the protective effects of coffee against liver fibrosis in SD rats. AB - BACKGROUND: Coffee is one of the most commonly consumed beverages worldwide. Accumulating clinical evidence has shown an inverse relationship between coffee and liver cirrhosis. We investigated the protective effect of coffee against liver fibrosis and underlying molecular mechanisms using a dimethylnitrosamine (DMN)-induced liver fibrosis model. RESULTS: Coffee administration significantly prevented the deterioration of body weight, organ weight, and serum biochemistry by DMN treatment. Histopathological examination revealed that necrosis/inflammation and fibrotic septa decreased significantly in coffee treated rats compared to those treated with DMN and water. Coffee administration also significantly inhibited the accumulation of hydroxyproline (P < 0.001) and the production of malondialdehyde (P < 0.05), as well as stellate cell activation caused by DMN injection. Coffee protected the depletion of glutathione, superoxide dismutase, and catalase in liver tissue. In addition, coffee treatment inhibited the gene expression of inducible nitric oxide synthase, transforming growth factor (TGF)-beta, tumor necrosis factor-alpha, interleukin-1, and platelet-derived growth factor (PDGF)-beta in liver tissues, and lowered the concentration of TGF-beta and PDGF-beta in liver. Coffee inhibited NO production by macrophages. CONCLUSION: Coffee exerts protective effects against liver fibrosis via antioxidant action and the suppression of fibrogenic cytokines, TGF beta and PDGF-beta. PMID- 20355068 TI - Evaluation of tropical plants containing tannin on in vitro methanogenesis and fermentation parameters using rumen fluid. AB - BACKGROUND: Methane (CH(4)) produced during ruminal fermentation represents a loss of 10-11% of gross energy intake. The use of browse species containing tannin as feed supplement for ruminants tends to increase in order to reduce CH(4) production. The present study was conducted to evaluate some tropical plants containing tannin as feed supplement (200 g kg(-1)) on in vitro CH(4) production and fermentation parameters. RESULTS: The crude protein (CP) content ranged from 87 to 390 g kg(-1) dry matter (DM) and was highest in Sesbania grandiflora (L.) Poiret. The neutral detergent fibre (NDF) concentration was highest in Pennisetum purpureum Schumach (725 g kg(-1) DM) and lowest in S. grandiflora (330 g kg(-1) DM). The ranking order of plants based on their total tannin content was Acacia mangium Willd. > Biophytum petersianum Klotzch > Jatropa curcas Linnaeus > Psidium guajava Linnaeus > Phaleria papuana > Persea americana Mill. > S. grandiflora. Methane gas production after 48 h of incubation was significantly (P < 0.05) lower with inclusion of A. mangium (PP + AM), B. petersianum (PP + BP), J. curcas (PP + JC) or P. guajava (PP + PG) as compared to control feed (PP). There was negative correlation between total tannin content and CH(4) production at 48 h of incubation (r = - 0.76). Concentration NH(3)-N was significantly (P < 0.01) higher with inclusion of S. glandiflora. Inclusion of P. guajava significantly (P < 0.05) suppressed protozoa population by 49.7% relative to control feed (PP). CONCLUSION: It was concluded that A. mangium, B. petersianum, J. curcas and P. guajava have potential to be used as a feed supplement to reduce CH(4) production in ruminants. PMID- 20355069 TI - The influence of organ, season and drying method on chemical composition and antioxidant and antimicrobial activities of Juniperus phoenicea L. essential oils. AB - BACKGROUND: Juniperus phoenicea is an important medicinal plant. In the present study, essential oils (18 samples) from leaves and berries of Juniperus phoenicea L. (Cupressaceae), obtained by various drying methods and in different collection months, were analysed by gas chromatography-mass spectrometry and also evaluated for in vitro antimicrobial and antioxidant activities. Correlations were studied between antimicrobial activity and the chemical composition of essential oils. RESULTS: Sixty-seven compounds were identified in essential oils, representing 97.7-100%. Essential oils were dominated by monoterpenes and sesquiterpenes, which presented 35.0-93.3% and 6.7-62.0%, respectively, depending of organ, season and drying method. Antimicrobial tests showed that essential oils strongly inhibited the growth of Gram-positive microorganisms and Mucor ramamnianus, but was inactive against Gram-negative strains. Antioxidant activity was tested using the ABTS radical-scavenging assay. Most samples showed good activity (the best IC(50) = 41.7 + or - 1.5 mg L(-1)). CONCLUSIONS: It could be concluded that drying of leaves of J. phoenicea in the sun and berries in oven-drying was more suitable and was recommended for obtaining higher essential oil yield, but for a higher percentage of some special components such as alpha-pinene and delta-3 carene shade-drying was more suitable. PMID- 20355070 TI - Effect of dietary level of methionine on growth performance and immune response in Japanese quails (Coturnix coturnix japonica). AB - BACKGROUND: Methionine (Met) being the first limiting amino acid in maize/soybean based quail diets, its supplementation provides scope for improvement of protein quality and reduction of dietary protein concentration. The question remains to what extent it can be incorporated in the diet of genetically improved quails. Therefore the effect of dietary Met level was assessed on growth performance and immune response in growing Japanese quails (n = 400) divided equally into 20 groups. Five dietary treatments (approximately 230 g kg(-1) crude protein and 12.14 MJ kg(-1) metabolisable energy) were formulated with 3.5, 4.5, 5.0, 5.5 and 6.0 g kg(-1) Met respectively, and each was offered to four groups of birds from 0 to 35 days of age. RESULTS: Live weight at day 35 increased (P < 0.0001) up to 5.0 g kg(-1) dietary Met level but did not improve further at higher Met levels (5.5 and 6.0 g kg(-1)). Improved (P < 0.039) feed conversion ratio was achieved at 5.5 g kg(-1) Met level, which was statistically similar to that at 5.0 g kg( 1) Met level during 0-14 days of age. Cellular (phytohaemagglutinin from Phaseolus vulgaris) immune response increased (P < 0.0001) with increasing dietary Met concentration, whereas humoral (sheep red blood cells) immune response did not differ. CONCLUSION: The optimal requirement of Met was 5.0 g kg( 1) for growth and 5.5 g kg(-1) for maximum cellular immune response. PMID- 20355071 TI - Steering nitrogen fertilisation by means of portable chlorophyll meter reduces nitrogen input and improves quality of fertigated cantaloupe (Cucumis melo L. var. cantalupensis Naud.). AB - BACKGROUND: Farming is considered one of the main causes of land degradation and underground water pollution. The increased availability of agricultural inputs has led to a dramatic rise in yields, which has resulted in soil fertility spoilage and overuse of fertilisers. Therefore horticultural practice improvement must consider appropriate nitrogen (N) management. This paper reports results on the application of an optical diagnostic system (N-tester) to guide N fertilisation in muskmelon (Cucumis melo L.) over a 3 year trial. Results on fresh and postharvest quality are also presented. RESULTS: Fertilisation events mirrored increases in N-tester values during the season, and a significant linear relationship (R(2) = 0.628) was observed between N-tester readings and leaf chlorophyll content. The N-tester-guided fertilisation treatments were characterised by yields comparable to the control, but with significantly lower applications of N (down to 17-66% of the N distributed in the control). Moreover, the N-tester treatments yielded fruits with higher sugar content. This was also true after storage, when N-tester fruits also showed reduced weight loss associated with lower transpiration and ethylene emission rates. CONCLUSION: Through the use of 'spy plots' kept at optimal nutritional status and the adoption of a threshold for N application throughout the growing cycle of muskmelon, the N supply was significantly reduced. Therefore a correct application of N-tester allowed the plant N requirement to be reduced and the fruit sugar content and storability to be increased without adversely affecting the yield. PMID- 20355072 TI - Impact of alpha-amylase and maltodextrin on physicochemical, functional and antioxidant capacity of spray-dried purple sweet potato flour. AB - BACKGROUND: Purple sweet potato flour could be used to enhance food products through colour, flavour and nutrients. Purple sweet potato flour has not yet been prepared with maltodextrin and amylase treatment using spray drying. Thus, the investigation was to evaluate the effect of various levels of maltodextrin (30 and 50 g kg(-1) w/v), amylase (3 and 7 g kg(-1) puree) and combined with maltodextrin and amylase on the physicochemical, functional and antioxidant capacity of spray dried purple sweet potato flours. RESULTS: Amylase and amylase with maltodextrin-treated flours had a higher anthocyanin and total phenolic content than the control and maltodextrin-treated flours. However, the antioxidant capacity was higher in the control and maltodextrin-treated flours compared to the amylase and amylase with maltodextrin-treated flours. The control had a higher water absorption index and lower water solubility index compared to the maltodextrin and combined with amylase and maltodextrin-treated flours. On the other hand, maltodextrin increased whereas alpha-amylase decreased the glass transition temperature. With respect to morphology, the particles of amylase treated flours were smaller than the control and maltodextrin-treated flours. CONCLUSION: The results showed that good quality flour could be prepared by combining 30 g kg(-1) maltodextrin and 7 g kg(-1) amylase treatment. PMID- 20355073 TI - Immunogold labelling to localize polyphenol oxidase (PPO) during wilting of red clover leaf tissue and the effect of removing cellular matrices on PPO protection of glycerol-based lipid in the rumen. AB - BACKGROUND: The enzyme polyphenol oxidase (PPO) reduces the extent of proteolysis and lipolysis within red clover fed to ruminants. PPO catalyses the conversion of phenols to quinones, which can react with nucleophilic cellular constituents (e.g. proteins) forming protein-phenol complexes that may reduce protein solubility, bioavailability to rumen microbes and deactivate plant enzymes. In this study, we localized PPO in red clover leaf tissue by immunogold labelling and investigated whether red clover lipid was protected in the absence of PPO induced protein-phenol complexes and plant enzymes (lipases). RESULTS: PPO protein was detected to a greater extent (P < 0.001) within the chloroplasts of mesophyll cells in stressed (cut/crushed and wilted for 1 h) than freshly cut leaves for both palisade (61.6 and 25.6 Au label per chloroplast, respectively) and spongy mesophyll cells (94.5 and 40.6 Au label per chloroplast, respectively). Hydrolysis of lipid and C18 polyunsaturated fatty acid biohydrogenation during in vitro batch culture was lower (P < 0.05) for wild-type red clover than for red clover with PPO expression reduced to undetectable levels but only when cellular matrices containing protein-phenol complexes were present. CONCLUSION: Damaging of the leaves resulted in over a doubling of PPO detected within mesophyll cells, potentially as a consequence of conversion of the enzyme from latent to active form. PPO reduction of microbial lipolysis was apparent in macerated red clover tissue but not in the absence of the proteinaceous cellular matrix, suggesting that the PPO mechanism for reducing lipolysis may be primarily through the entrapment of lipid within protein-phenol complexes. PMID- 20355074 TI - Effects of extracts of spices on rumen methanogenesis, enzyme activities and fermentation of feeds in vitro. AB - BACKGROUND: An experiment was conducted to study the effects of boiling water, methanol and ethanol extracts (0, 0.25 and 0.50 mL) of seeds of Foeniculum vulgare (fennel), flower buds of Syzygium aromaticum (clove), bulbs of Allium sativum (garlic), bulbs of Allium cepa (onion) and roots of Zingiber officinalis (ginger) on rumen methanogenesis, fibrolytic enzyme activities and fermentation characteristics in vitro. RESULTS: Ethanol and methanol extracts of fennel, clove and garlic at 0.50 mL and clove at 0.25 mL inhibited (P < 0.05) methane production. Carboxymethylcellulase activity was reduced (P < 0.05) by ethanol and methanol extracts (0.50 mL) of fennel and clove (0.25 and 0.50 mL). The extracts of clove reduced (0.25 and 0.50 mL) xylanase and acetylesterase activities, and the fennel extract (0.50 mL) reduced (P < 0.05) xylanase activity. However, the extracts of garlic (0.50 mL) increased (P < 0.05) acetylesterase activity. Concentrations of volatile fatty acids were reduced (P < 0.05) by the extracts of garlic and onion. The extracts of garlic caused a decrease (P < 0.05) in acetate:propionate ratio (A:P) at 0.50 mL, whereas A:P was increased (P < 0.05) by the inclusion of 0.50 mL extracts of clove. Methanol and ethanol extracts of clove decreased (P < 0.05) in vitro organic matter degradability. Extracts (0.50 mL) of clove decreased (P < 0.05) the numbers of total protozoa, small entodiniomorphs and holotrichs, whereas extracts of onion, ginger and garlic enhanced (P < 0.05) protozoal numbers (both entodiniomorphs and holotrichs). CONCLUSION: Ethanol and methanol extracts of fennel and garlic have potential to inhibit rumen methanogenesis without adversely affecting rumen fermentation. PMID- 20355075 TI - Timing clorpirifos + cypermethrin and indoxacarb applications to control European corn borer damage and fumonisin contamination in maize kernels. AB - BACKGROUND: European corn borer (ECB) is the main maize pest in central and southern Europe and it promotes the infection of maize with Fusarium verticillioides, which is able to produce fumonisins. Field experiments were performed from 2006 to 2007 in northwestern Italy to determine the effects of the timing of insecticide applications on maize fungal ear rot and fumonisin contamination in natural infection conditions. Four application timings and two insecticides (clorpirifos + cypermethrin and indoxacarb) were compared each year. RESULTS: In both years, the treatments applied at the beginning of a consistent ECB flight activity and at the flight peak showed the best efficacy to control the insect damage on ears. Fungal ear rot and fumonisin contamination were clearly affected by ECB control. The efficacy of the best application timing to control fumonisin occurrence was 73% in 2006 and 84% in 2007. Earlier insecticide applications showed lower fumonisin contamination than treatments applied after the adult flight peak. CONCLUSION: The production of maize and maize-based foods with a low fumonisin content may be enhanced through correct insecticide application against the second ECB generation. The optimum timing of insecticides is between the beginning of a consistent adult flight activity and the flight peak. PMID- 20355076 TI - Effect of different high pressure treatments on shucking, biochemical, physical and sensory characteristics of oysters to elaborate a traditional Taiwanese oyster omelette. AB - BACKGROUND: Whole oysters (Crassostrea gigas) were processed using high-pressure (HP) treatment (150-300 MPa) to determine their shucking and biochemical properties. Subsequently, HP-treated oysters were cooked at 160 degrees C for 90 s, as when preparing the oyster omelette dish, to evaluate their physical and sensory characteristics as compared to raw oysters. RESULTS: The treatments of 250 and 300 MPa for 2 min and 0 min, respectively, resulted in 100% release. The pH of HP-treated oysters increased slightly from 6.50 to 6.82, and the moisture contents of the HP-treated oysters with or without further cooking were all higher than those of the control. The brightness, yellowness and cutting strength of HP-treated oysters with further cooking changed insignificantly, while the redness decreased compared to the control. Sensory evaluation showed that oysters treated at 250 and 300 MPa oysters after cooking received higher quality scores than the control. CONCLUSIONS: HP processing at 250 and 300 MPa proved to be a good method for oyster shucking. The HP-treated oysters cooked in the oyster omelette are acceptable to consumers. Overall, the application of HP as a processing method to improve the quality and acceptability of oysters and their related products would be possible. PMID- 20355077 TI - Low oxygen treatment prior to cold storage decreases the incidence of bitter pit in 'Golden Reinders' apples. AB - BACKGROUND: The effect of subjecting 'Golden Reinders' apples to a low O(2) pre treatment (LOT; 1-2% O(2)) was evaluated as a strategy to decrease the rate of bitter pit (BP) incidence after standard cold storage (ST). Immediately after harvest, apples were stored for 10 days at 20 degrees C under low O(2). Thereafter, apples were cold-stored (0-4 degrees C) for 4 months and changes were monitored in terms of BP incidence, fruit quality traits and mineral element concentrations. RESULTS: After 4 months cold storage, LOT apples presented a 2.6 fold decrease in the rate of BP incidence (14%) versus the values obtained for standard cold-stored fruits (37% BP incidence). LOT increased flesh firmness, total soluble solids and titratable acidity as compared to the quality traits determined for cold-stored fruits. Lower cortex Ca and Mg concentrations as compared to ST apples were determined in association with LOT, 2 months after cold storage. CONCLUSION: Application of a LOT prior to cold storage may be a promising strategy to reduce the incidence of BP and preserve fruit quality, which should be further investigated. PMID- 20355079 TI - Effect of fat replacers on kefir quality. AB - The purpose of the study was to determine the effects of fat replacers on the quality of non-fat kefir. Skim milk fortified with Dairy Lo (DL) and inulin (INU) was fermented with kefir grains to manufacture kefir. The results of compositional, microbiological, rheological and sensorial analyses were compared with whole kefir (WK) and non-fat kefir (NFK) controls. Results for dry matter, pH and lactic acid ranged between 82.4 and 109.1 g kg(-1), 4.26 and 4.40, and 7.0 and 9.2 g L(-1), respectively. Acetaldehyde and ethanol contents of samples were between 2.89 and 7.28 mg L(-1), and 151.46 and 323.89 mg L(-1), respectively. In all samples, Lactobacillus spp., Streptococcus spp. and yeast counts were between 9.1 and 9.9, 9.3 and 9.9, and 5.2 and 5.6 log cfu mL(-1), respectively. Kefir samples had non-Newtonian behaviour and pseudoplastic fluid with thixotropy. At the first day, DL had the highest apparent viscosity (3.119 Pa s) while NFK had the lowest value (1.830 Pa s). In the sensory evaluation, odour and taste scores of samples were not different. Dairy Lo and inulin could be used without any adverse effect for the production of non-fat kefir. PMID- 20355080 TI - 1-Methylcyclopropene affects the antioxidant system of apricots (Prunus armeniaca L. cv. Bulida) during storage at low temperature. AB - BACKGROUND: Apricots (Prunus armeniaca cv. Bulida) were treated with 1 MUL L-1 [corrected] 1-methylcyclopropene (1-MCP) immediately after harvest and stored in air at 2 degrees C for 21 days. Antioxidant levels (ascorbic acid and carotenoids), enzymatic antioxidant activities (superoxide dismutase (SOD) and unspecific peroxidase (POX)) and total antioxidant capacity (trolox equivalent antioxidant capacity (TEAC)) were determined. The level of oxidative stress was also established by measuring ion leakage during storage. The changes in the antioxidant potential of apricots were related to the capacity of 1-MCP to increase their commercial life. RESULTS: 1-MCP-treated fruits exhibited higher SOD activity, whereas POX activity was significantly higher only after 21 days at 2 degrees C. Treated fruits also exhibited better retention of ascorbate and carotenoids and higher TEAC during storage. In accordance with these observations, lower ion leakage values were detected in 1-MCP-treated apricots. CONCLUSION: Taken together, these results suggest that 1-MCP conferred a greater resistance to oxidative stress. This, along with the reduction in ethylene production, could contribute to the increase in commercial life and nutritional value observed in 1-MCP-treated apricots. PMID- 20355081 TI - Mycotoxin profiles in the grain of Triticum monococcum, Triticum dicoccum and Triticum spelta after head infection with Fusarium culmorum. AB - BACKGROUND: The aim of study was to investigate mycotoxin profiles in the grain of spring lines of Triticum monococcum (12 lines), T. dicoccum (13 lines) and T. spelta (five lines), in comparison to the T. aestivum cultivar Sumai-3 which is resistant to Fusarium head blight. The grain was obtained from control heads and heads artificially inoculated in the field with Fusarium culmorum. Mycotoxins were determined by LC-MS/MS. RESULTS: A total of 11 toxins were identified in control grain samples. Deoxynivalenol (DON) concentrations exceeded 0.5 mg kg(-1) in only three samples of T. monococcum grain and in one sample of T. dicoccum grain. Inoculation with F. culmorum resulted in a substantial increase in the concentrations of DON (to 63 mg kg(-1)) in the T. monococcum and DON-3-glucoside (to 5.6 mg kg(-1)) in the T. dicoccum. Inoculation contributed to a drop in tentoxin levels (by 57% in T. spelta) and to an increase of cyclodepsipeptide concentrations (in particular enniatins B and B(1)) being two-fold (T. monococcum) to four-fold (T. dicoccum) higher on average than in control samples. The Sumai-3 responded to inoculation with nearly a two-fold drop in the levels of the cyclodepsipeptides. CONCLUSION: The results of a discriminant analysis for all identified toxins indicate that einkorn, emmer and spelt differ significantly with regard to the mycotoxin profiles of their grain. PMID- 20355082 TI - Production of maize-bambara groundnut complementary foods fortified pre fermentation with processed foods rich in calcium, iron, zinc and provitamin A. AB - BACKGROUND: Maize-bambara groundnut complementary foods are deficient in calcium, iron, zinc and vitamin A. Food-to-food fortification could be cheaper, safer and more easily adopted by local communities compared to the use of chemically pure compounds and vitamins to enrich such foods. RESULTS: Maize-bambara groundnut complementary foods fortified for iron, zinc, calcium and vitamin A by blending with a multi-mix (1.41:1:2.25, w/w) of processed roselle calyces, cattle bones, and red palm oil in a 1:2.1 (w/w) ratio showed significant increases in calcium, iron, zinc and vitamin A contents of 3.26-4.225, 0.083-0.134 and 0.015-0.017 g kg(-1) and 4855.3-7493.7 microgRE kg(-1), respectively. CONCLUSION: The maize bambara groundnut foods had calcium, iron, zinc and vitamin A contents that satisfy the proposed nutrient requirements for infants. Only the maize-bambara groundnut and maize-bambara groundnut malt fermented by backslopping [(MB)(b) and (MB(m))(b)] containing red palm oil emulsified with Brachystegia eurycoma had calcium contents significantly (P < 0.05) higher than Nutrend, a complementary food produced by Nestle (Nigeria) PLC. These products are from raw materials produced in commercial quantities by rural farmers using household level technologies which the rural and urban poor can more easily access in order to reduce micronutrient malnutrition. PMID- 20355083 TI - In vitro digestion of fresh alfalfa under different conditions of ruminal pH. AB - BACKGROUND: Relatively low ruminal pH values have been frequently registered in dairy cows grazing alfalfa, which can be involved in reducing feed digestion. An in vitro experiment was carried out to study the effect of ruminal pH (6.4, 6.1, 5.8 and 5.5) on the digestion of fresh alfalfa. RESULTS: Decreasing the pH, in vitro gas production (ivGP) decreased (P < 0.05). The lowest ivGP was registered at pH 5.5 and it was product of a higher lag time and a lower digestion rate. Dry matter disappearance (DMD) was not affected by pH at 48 h (P > 0.05). Neutral detergent disappearance (NDFD) at 48 h decreased below pH 6.1. The NDFD was reduced by 62% at pH 5.5 with respect to results at pH 6.4 and 6.1 (where the highest DMD and NDFD were observed). CONCLUSION: As expected, low rumen pH decreased alfalfa digestion. However, limits to ruminal digestion activity differed from those usually proposed for TMR diets. It is apparent that different relationships between rumen pH and NDFD exist when cows graze fresh alfalfa or grasses. Moreover, our results suggest the convenience to complement the data obtained through ivGP, DMD and NDFD. While ivGP and DMD seem to be more useful at early digestion times, NDFD may be a good predictor of final digestion. PMID- 20355084 TI - Effect of short-term air storage after removal from controlled-atmosphere storage on apple and fresh-cut apple quality. AB - BACKGROUND: One of the realities of apple distribution for long-term stored fruit is that a controlled-atmosphere (CA) storage room will be unsealed and fruit held in air storage and marketed over several weeks. This work was conducted to determine the effect of post-CA air storage of whole fruit on potential shelf life for fresh-cut apple slices. RESULTS: Fresh-cut slices of 'Spartan' and 'Delicious' apples held in post-CA air storage for 2 or 4 weeks showed the least changes in cut surface color as compared with those made from apples immediately on removal from CA. Shelf life was most improved by post-CA air storage in the 'Spartan' apples, which were more advanced in maturity as compared with the 'Delicious' apples. Internal ethylene concentration, firmness, and respiration changed significantly with post-CA air storage, suggesting a relationship between physiological status of the whole fruit and shelf life of slices made from that fruit. CONCLUSION: The results support the hypothesis that apples had suppressed physiological activity in CA storage and are susceptible to accelerated deterioration upon cutting. Holding fruit for 2 weeks in air storage allowed recovery of physiological activity, which resulted in greater resistance to deterioration in response to fresh-cut processing. PMID- 20355085 TI - Improvement of the quality and abatement of the biogenic amines of grass carp muscles by fermentation using mixed cultures. AB - BACKGROUND: To improve the quality of processed grass carp (Ctenopharyngodon idellus) products and control the accumulation of hazardous substances therein, minced grass carp slices were salted for 6 h at room temperature and then inoculated with mixed starter cultures of Lactobacillus casei, Streptococcus lactis, Saccharomyces cerevisiae Hansen and Monascus anka and fermented for 12 h at 30 degrees C. The changes in some characteristics and biogenic amine contents of the fermented muscles were investigated. RESULTS: During the 12 h fermentation at 30 degrees C, muscles inoculated with mixed starter cultures showed a rapid decrease in pH from 6.0 to 5.1 and suppression of the growth of enterobacteria and pseudomonads. The fermented muscles exhibited better colour, appearance, flavour and overall acceptability than the control (P < 0.05). The changes in non protein nitrogen and free amino acid contents of the fermented muscles and in their sodium dodecyl sulfate polyacrylamide gel electrophoresis profiles indicated that severe hydrolysis of muscle proteins occurred during fermentation. The accumulation of biogenic amines in the muscles was efficiently reduced by fermentation with mixed starter cultures. CONCLUSION: Fermentation with mixed starter cultures of L. casei, S. lactis, S. cerevisiae Hansen and M. anka significantly improved the characteristics of grass carp muscles and controlled the accumulation of biogenic amines. PMID- 20355086 TI - The effect of gaseous ozone treatment on egg components. AB - BACKGROUND: Because of the salmonella problem in poultry, disinfection technologies are necessary. Ozone is a strong oxidant used for the disinfection of surfaces, drinking water and foods. However, since ozone not only destroys bacteria but may also damage eggs, it is necessary to clarify the effects of ozone treatment on hatching egg components. In this study, doses of gaseous ozone ranging from 10 to 50 mL L(-1) were tested. The vitamin A and E contents and fatty acid composition of the egg yolk were determined. To detect possible damage to the DNA of the germ disc, single-cell gel electrophoresis was used. Moreover, free SH groups were measured in the egg white. The soluble cuticula proteins were analysed by polyacrylamide gel electrophoresis. RESULTS: The yolk was not significantly affected by ozone treatment. However, the DNA of the germ disc was attacked and a significant decrease in free SH groups in the egg white was recorded at 50 mL L(-1) ozone. Even at low ozone doses the soluble cuticula proteins were completely destroyed. CONCLUSION: Significant alterations of egg components were caused by 50 mL L(-1) ozone. At lower ozone doses the oxidative processes occurred mainly at the egg surface and are therefore probably harmless to the developing embryo. PMID- 20355087 TI - Functional and conformational properties of phaseolin (Phaseolus vulgris L.) and kidney bean protein isolate: a comparative study. AB - BACKGROUND: Kidney bean (Phaseolus vulgris L.) seed is an underutilised plant protein source with good potential to be applied in the food industry. Phaseolin (also named G1 globulin) represents about 50 g kg(-1) of total storage protein in the seed. The aim of the present study was to characterise physicochemical, functional and conformational properties of phaseolin, and to compare these properties with those of kidney bean protein isolate (KPI). RESULTS: Compared with kidney bean protein isolate (KPI), the acid-extracted phaseolin-rich protein product (PRP) had much lower protein recovery of 320 g kg(-1) (dry weight basis) but higher phaseolin purity (over 950 g kg(-1)). PRP contained much lower sulfhydryl (SH) and disulfide bond contents than KPI. Differential scanning calorimetry analyses showed that the phaseolin in PRP was less denatured than in KPI. Thermal analyses in the presence or absence of dithiothreitol, in combination with SH and SS content analyses showed the contributions of SS to the thermal stability of KPI. The analyses of near-UV circular dichroism and intrinsic fluorescence spectra indicated more compacted tertiary conformation of the proteins in PRP than in KPI. PRP exhibited much better protein solubility, emulsifying activity index, and gel-forming ability than KPI. The relatively poor functional properties of KPI may be associated with protein denaturation/unfolding, with subsequent protein aggregation. CONCLUSION: The results presented here suggest the potential for acid-extracted PRP to be applied in food formulations, in view of its functional properties. PMID- 20355088 TI - Antiaflatoxigenic and antioxidant activity of an essential oil from Ageratum conyzoides L. AB - BACKGROUND: Aflatoxin contamination of various commodities can occur as a result of infection, mainly by Aspergillus flavus and Aspergillus parasiticus. Every year, almost 25% of the world's food supply is contaminated by mycotoxins. Aflatoxins B(1), B(2), G(1) and G(2), which occur naturally, are significant contaminants of a wide variety of commodities. A number of biological activities have been associated with Ageratum conyzoides. We have therefore investigated the antiaflatoxigenic, antioxidant and antimicrobial activity of essential oils of A. conyzoides. This could help to turn A. conyzoides, a nuisance weed, into a resource. RESULTS: The essential oil of Ageratum conyzoides L. shows the presence of 12 compounds when analyzed by gas chromatography-mass spectrometry. The growth and aflatoxin production of the toxigenic strain Aspergillus parasiticus was completely inhibited by essential oil. All the studied concentrations of the oil demonstrate a reduction in mycelia growth and decreased production of different aflatoxins in fungi, as revealed by liquid chomatographic-tandem mass spectrometric analysis. Volatiles from macerated green leaf tissue of A. conyzoides were also effective against A. parasiticus. The strongest antibacterial activity was observed against the bacteria Staphylococcus aureus and Bacillus subtilis in a disk diffusion bioassay. Essential oil and methanol extract of A. conyzoides L. were assayed for their antioxidant activity. Methanol extract showed the highest antioxidant activity in FRAP and DPPH assay, whereas essential oil showed greater lipid peroxidation inhibition than methanol extract. CONCLUSION: The plant's ethno-medicinal importance, antioxidant potential, inhibitory activity against the Aspergillus group of fungi and production of aflatoxins may add a new dimension to its usefulness in the protection of stored product. PMID- 20355089 TI - Induction of apoptosis by tomato using space mutation breeding in human colon cancer SW480 and HT-29 cells. AB - BACKGROUND: As far as we know, there have been no reports concerning the functional characteristics of tomatoes using space mutation breeding. The aim of this study was to evaluate the anti-colon cancer effect of tomatoes M1 and M2 using space mutation breeding. RESULTS: In the present study, obvious anti-cancer activity was shown with tomato juice of M1 and M2 and their parent CK treatment in colon cancer cell lines SW480 and HT-29 in cell growth inhibition. In addition, SW480 cells were more sensitive to M1 and M2 than HT-29 cells in cell apoptosis. Furthermore, M1 and M2 induced cell cycle arrest both in G0-G1 and G2/M phases. CONCLUSION: These data suggest that consumption of tomato using space mutation breeding may provide benefits to inhibit growth of colon cancer cells. Therefore, tomato production using space mutation breeding may be a good candidate for development as a dietary supplement in drug therapy for colon cancer. PMID- 20355090 TI - Effect of drying and storage on the degradation of total carotenoids in orange fleshed sweetpotato cultivars. AB - BACKGROUND: Orange-fleshed sweetpotato (OFSP) can be used to tackle vitamin A deficiency, a major public health problem in most developing countries. In East Africa, common ways of using sweetpotato include drying and subsequent storage. The aim of the study was to investigate the impact of drying and storage on the total carotenoid retention (as an estimate of provitamin A retention) from OFSP. RESULTS: Losses of total carotenoid during drying were generally low (15% or less). Total carotenoid retention in OFSP was not dependent on the type of dryer (solar or sun). Sweetpotato cultivar (Ejumula, Kakamega, SPK004/1, SPK004/1/1, SPK004/6 or SPK004/6/6) had a significant effect on retention in drying (P < 0.05). High percentage losses of total carotenoids were, however, correlated with high moisture content and high carotenoid content in fresh sweetpotato roots. After 4 months' storage at room temperature in Uganda, losses of total carotenoid in dried sweetpotato chips were high (about 70%) and this was not dependent on the use of opaque or transparent packaging. CONCLUSION: Losses of carotenoids during storage were considered to be more of a nutritional constraint to the utilisation of dried sweetpotato than losses occurring during drying. The relationship between characteristics of the cultivars and losses of carotenoids during drying should be taken into account in selection of cultivars for processing. PMID- 20355091 TI - Synergistic effect of oligochitosan and silicon on inhibition of Monilinia fructicola infections. AB - BACKGROUND: Oligochitosan has broad-spectrum antimicrobial activity and shows an obvious inhibitory effect on phytopathogens. In addition, as an exogenous elicitor, it can induce various defence responses, including affecting the activities of several defence-related enzymes and substances in some plants. Owing to this dual function of oligochitosan, it can be used to control postharvest diseases of fruits. Silicon, like oligochitosan, also has a dual function. In this study the synergistic effect of oligochitosan and silicon on the decay control of apple fruit was investigated. RESULTS: In vitro, both oligochitosan and silicon significantly inhibited spore germination, germ tube elongation and mycelial growth of Monilinia fructicola, with higher concentrations having a greater effect. The synergistic effect of oligochitosan and silicon at half-maximal inhibitory concentration on disease control at 25 degrees C was much better than the effect of oligochitosan or silicon alone, not only in vitro but also in vivo. CONCLUSION: The results showed that a combination of oligochitosan and silicon had a synergistic effect on the control of disease caused by M. fructicola in apple fruit at 25 degrees C. PMID- 20355092 TI - Enzymatic hydrolysis of Alaska pollack (Theragra chalcogramma) skin and antioxidant activity of the resulting hydrolysate. AB - BACKGROUND: Fish skin, a by-product of the food industry, contains a large amount of collagen. However, only a small proportion of fish skin is used in the production of leather materials and animal feedstuffs, most of it being discarded. The aims of this study were to prepare peptides from Alaska pollack (Theragra chalcogramma) skin by enzymatic hydrolysis and to evaluate the antioxidant activity of the resulting hydrolysate. RESULTS: Protamex was the most efficient enzyme for preparing antioxidant peptides from Alaska pollack skin. The optimal hydrolysis conditions were as follows: hydrolysis time 8 h; enzyme/substrate ratio 2:1000; skin/water ratio 1:6; temperature 55 degrees C; pH 6.0. Under these conditions the highest yield of peptides was 83.44%, with 85.95% of the hydrolysate being mainly composed of oligopeptides with molecular weights ranging from 180 to 1000 Da. The hydrolysate showed 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, with an IC(50) value of 2.5 mg mL(-1), and its reducing power was 0.14 at 1 mg mL(-1), 53.8% of that of reduced glutathione at the same concentration. CONCLUSION: This study demonstrated that the hydrolysate of Alaska pollack skin was mainly composed of oligopeptides with two to eight amino acid residues and possessed antioxidant activity. PMID- 20355093 TI - Air analysis in the assessment of fumonisin contamination risk in maize. AB - BACKGROUND: In maize-growing areas where fumonisin contamination is endemic, there is an urgent need for novel methods to assess the quality of grain lots before their delivery to common drying and storage collection centres. Aerobiological samples of fungal spores released during harvest were analysed to establish a relationship between fumonisin contamination and the abundance of pathogen propagules collected in the combine harvester using a cyclone and membrane filters. Filter-captured propagules were analysed by direct plating, immunoenzymatic assay of specific Fusarium extracellular polysaccharides and real time polymerase chain reaction of the extracted DNA using fum1, a gene involved in the biosynthesis of fumonisin, as a target. RESULTS: The results showed that time of harvest and environmental conditions strongly influenced the efficiency and performance of the collection system. The data obtained were informative in comparing individual samples collected under similar conditions. The immunoenzymatic assay provided the most reliable data, which improved the ability of a neural network to predict the fumonisin content of lots, when added to agronomic, environmental and phytosanitary data. CONCLUSION: This is the first attempt to evaluate the Fusarium propagules dispersed during harvesting as a predictive means to assess maize quality. A method based on cyclone/filter capture and immunological detection has been shown to be feasible and to have the potential for the development of a continuous monitoring system, but the prediction capabilities in the present implementation were limited. PMID- 20355094 TI - Biodegradation of genetically modified seeds and plant tissues during composting. AB - BACKGROUND: The increasing global market of genetically modified (GM) crops amplifies the potential for unintentional contamination of food and feed with GM plants. Methods proposed for disposal of crop residues should be assessed to prevent unintended distribution of GM materials. Composting of organic material is inexpensive and location-independent. The objective of this study was to determine the effectiveness of composting for disposal of GM plants in terms of reducing seed viability and promoting the degradation of endogenous as well as transgenic DNA. RESULTS: Duplicate samples of corn kernels, alfalfa leaves, and GM canola seeds, meal and pellets were sealed in porous nylon bags and implanted in duplicate 85,000 kg (initial weight) feedlot manure compost piles. Samples were collected at intervals over 230 days of composing. Canola seeds and corn kernels were not viable after 14 days of composting with temperatures in the piles exceeding 50 degrees C. In all samples, PCR analyses revealed that plant endogenous and transgenic fragments were substantially degraded after 230 days of composting. Southern blotting of genomic DNA isolated from canola seeds identified differences in the persistence of endogenous, transgenic, and bacterial DNA. CONCLUSION: Composting GM and non-GM plant materials with manure rendered seeds non-viable, and resulted in substantial, although not complete, degradation of endogenous and transgenic plant DNA. This study demonstrates that composting could be effective for disposing of GM crops in the event of their inadvertent entry into the food or feed chain. PMID- 20355095 TI - Enhanced water absorption of wheat gluten by hydrothermal treatment followed by microbial transglutaminase reaction. AB - BACKGROUND: The water absorption of wheat gluten plays an important role in the weight, volume and form ratio of the breads. In this paper, hydrothermal treatment and microbial transglutaminase (MTGase) modification were combined to improve the water absorption ratio (WAR) of wheat gluten. To understand the increases in WAR, the changes in MTGase reaction after gluten hydrothermal treatment were also investigated. RESULTS: The sole hydrothermal treatment improved the WAR of gluten. The gluten treated at 100 degrees C for 30 min exhibited the highest WAR value (2.03 g g(-1) gluten) while the WAR of the control without hydrothermal treatment was 1.5 g g(-1) gluten. When gluten was exposed to 90 degrees C for 30 min followed by incubation with MTGase for 5 h, its WAR reached 2.48 g g(-1) gluten. In contrast to control gluten, the surface hydrophobicity of the gluten preheated at 90 degrees C for 30 min increased and fluctuated in a different way during the following MTGase reaction. Meantime, the trend in the amount of soluble protein of preheated gluten was also changed in the progress of MTGase reaction. CONCLUSION: Hydrothermal treatment followed by MTGase reaction is an efficient approach to improve the WAR of wheat gluten. The analysis of catalytic process, including determination of ammonia, gluten surface hydrophobicity, soluble protein and SDS-PAGE, suggested that hydrothermal pretreatment accelerated the cross-linking reaction and may alter the ratio of gluten deamidation catalysed by MTGase, which induced an increase in the WAR. PMID- 20355096 TI - Essential oil yield and composition of Pistacia vera 'Kerman' fruits, peduncles and leaves grown in California. AB - BACKGROUND: Pistacia vera 'Kerman' is the predominant pistachio nut cultivar in the United States (California), the world's second largest producer. Despite several reports on the essential oil (EO) content in the genus Pistacia, data on 'Kerman' are limited. The EO content and volatile organic compound (VOC) emissions of tree nut orchards are of current interest to researchers investigating insect pests and the potential role of EO and VOCs as semiochemicals. To establish a basis for the VOC output of pistachios, the EO content of fruits, peduncles, and leaves was analyzed. RESULTS: Evaluated plant parts contained limonene as the primary EO component, followed by alpha terpinolene. Peduncles were unique in containing relatively high levels of alpha thujene. The results were reproducible between two different geographical locations. In situ solid phase microextraction (SPME) studies demonstrated the volatile emission was representative of the EO composition. CONCLUSION: This is the first report detailing the content and distribution of EO and the unique limonene-dominant profile for this Pistacia vera cultivar which may influence pistachio insect pest semiochemical research. PMID- 20355097 TI - Purification of calmodulin from rice bran and activation of glutamate decarboxylase by Ca2+/calmodulin. AB - BACKGROUND: gamma-Aminobutyric acid (GABA) is an important bioactive regulator, and its biosynthesis is primarily through the alpha-decarboxylation of glutamate by glutamate decarboxylase (GAD). In plants, it was verified that the production of GABA is regulated, in part, via Ca(2+)/calmodulin (CaM). Our preliminary studies showed that rice bran GAD is probably also a Ca(2+)/CaM dependent enzyme; hence, in the current investigation, we purified calmodulin from rice bran, and studied the effect of the Ca(2+)/calmodulin complex on the activity of rice bran GAD in vitro. RESULTS: CaM was purified to homogeneity from the rice bran by a combined protocol involving TCA precipitation, heat treatment, and hydrophobic interaction chromatography, with the purification fold and recovery of 851.7 and 55.6%, respectively. This protein had similar amino acid composition as the CaMs from other higher plants. The rice bran GAD was found to be quite sensitive to the Ca(2+)/CaM complex at pH 7.0, and addition of exogenous EGTA or TFP efficiently inhibited the stimulatory effect of Ca(2+)/CaM complex. At a separate concentration of Ca(2+) and CaM of 200 micromol L(-1) and 150 nmol L(-1), the rice bran GAD was significantly enhanced 3-fold. Moreover, upon binding Ca(2+), CaM underwent a conformational change that facilitated a more obvious emergency of phenylalanine and tyrosine residues. CONCLUSION: This investigation provided preliminary information for the development of a GABA-based, cost-effective rice bran GAD-related functional food. PMID- 20355098 TI - Polyphenol oxidase activity of two olive (Olea europaea L.) cultivars as an early criterion of Mn toxicity. AB - BACKGROUND: The time course of polyphenol oxidase (PPO) activity in the leaves of two olive cultivars (Picual and FS-17) irrigated with nutrient solutions differing in Mn concentration (0, 2 and 1280 micromol L(-1)) was studied under hydroponic conditions to determine whether PPO activity could be used as an early criterion of Mn status of olive plants, and to elucidate whether genotypic differences exist between the two olive cultivars studied, concerning the effect of Mn concentration on PPO activity. RESULTS: In all the Mn treatments, PPO activity was greater in Picual than in FS-17. Under excess Mn (1280 micromol L( 1)), PPO activity gradually increased with time, starting from day 30 of the experiment in both cultivars, and this increase preceded the appearance of Mn toxicity symptoms. In contrast, in the other two Mn treatments (0 and 2 micromol L(-1)) PPO activity increased and afterwards decreased during the experiment, but the trend was not clear. In the 1280 micromol L(-1) treatment, PPO activity linearly increased (R = 0.8836 for Picual and 0.943 for FS-17) with the increase of Mn concentration in the leaves of both cultivars. In the 1280 micromol L(-1) Mn treatment, PPO activity was negatively related with Fe and Zn concentrations in the leaves, and positively in the 0 and 2 micromol L(-1) Mn treatments with the Ca, Mg and K concentrations. CONCLUSION: From the differential time course of PPO activity in the three Mn treatments (0, 2 and 1280 micromol L(-1)), it is concluded that periodic measurements of PPO activity in the leaves of the olive cultivars Picual and FS-17 can be used for the early detection of Mn toxicity (before the appearance of symptoms). PMID- 20355099 TI - Effect of ethylene and 1-MCP treatments on strawberry fruit ripening. AB - BACKGROUND: Strawberry is a soft fruit, considered as non-climacteric, being auxins the main hormones that regulate the ripening process. The role of ethylene in strawberry ripening is currently unclear and several studies have considered a revision of the possible role of this hormone. RESULTS: Strawberry fruit were harvested at the white stage and treated with ethephon, an ethylene-releasing reagent, or 1-methylcyclopropene (1-MCP), a competitive inhibitor of ethylene action. The effects of the treatments on fruit quality parameters and on the activity of enzymes related to anthocyanin synthesis and cell wall degradation were evaluated. Some aspects of ripening were accelerated (anthocyanin accumulation, total sugar content and increment of phenylalanine ammonia-lyase (PAL; EC 4.3.1.24) and beta-galactosidase (EC 3.2.1.23) activities), while others were repressed (chlorophyll levels and increment of endo-1,4-beta-glucanase (EC 3.2.1.4) and beta-xylosidase (EC 3.2.1.37) activities) or unchanged (reducing sugar content, pH, titratable acidity and alpha-L-arabinofuranosidase (EC 3.2.1.55) activity) by ethylene. 1-MCP treatment caused the opposite effect. However, its effects were more pronounced, particularly in anthocyanin accumulation, phenolics, PAL and polygalacturonase (EC 3.2.1.15 and EC 3.2.1.67) activities. CONCLUSION: These observations probably indicate that strawberry produces low levels of ethylene that are sufficient to regulate some ripening aspects. PMID- 20355100 TI - The effects of steaming and roasting treatments on beta-glucan, lipid and starch in the kernels of naked oat (Avena nuda). AB - BACKGROUND: Normal pressure steaming (NPS), autoclaved steaming (AS), and hot-air roasting (HAR) are widely used to deactivate oat enzyme in the oat-processing industry. Infrared roasting (IR) is a new oat deactivation method, and is welcomed and employed by increasing numbers of oat-processing plants in China. It is widely known that oat starch plays an important role in the processing function of oat food, and that oat beta-glucan and lipid contribute greatly to the health benefits of oat food. However, the effects of steaming and roasting treatments on the starch, beta-glucan and lipid in oat kernels are poorly known. RESULTS: In this research, the level and distribution of beta-glucan and lipid in oat kernels with and without deactivation treatments were tested. We also measured the viscosity properties of oat flour from kernels after NPS, AS, HAR and IR treatments, and examined the effects of these treatments on oat starch granularity using scanning electron microscopy. The results showed that the deactivation treatments did not have significant effects on oat beta-glucan and lipid levels in oat kernels (P < 0.01). The distribution of beta-glucan and lipid in enzyme-deactivated kernels was very similar to that in normal kernels. NPS, AS, HAR and IR treatments changed the shape of starch granules, crumbled large starch granules, reduced the connection between the protein network and starch granules, and improved starch gelatinization properties. CONCLUSIONS: NPS, AS, HAR and IR treatments can change the structure of oat starch granules and improve the viscosity property of oat starch without causing beta-glucan and lipid loss to oat food. PMID- 20355101 TI - Effects of foliar fertilization and arbuscular mycorrhizal colonization on Salvia officinalis L. growth, antioxidant capacity, and essential oil composition. AB - BACKGROUND: The effect of foliar fertilization and Glomus intraradices inoculation on the growth, qualitative and quantitative pattern of essential oil in Salvia officinalis was determined. Sage plants were grown in a glass house on a soil/sand mixture (w/w = 3:1). Agroleaf total, N:P:K = 20:20:20 + microelements, was used at the whole vegetative growth stage as a 0.3% solution. Inoculation with Glomus intraradices was done at the sowing stage. RESULTS: Application of foliar fertilization and/or mycorrhizal colonization improved dry biomass accumulation and increased the content of antioxidant metabolites (ascorbate and reduced glutathione). Applied treatments lowered the activities of the antioxidants enzymes catalase, ascorbate peroxidase and superoxide dismutase, while guaiacol peroxidase increased. The relative quantity of essential oil pattern was also altered as a result of the applied treatments. Combined application (FF + Gi) significantly promoted 1,8-cineole and alpha-thujone, mycorrhizal colonization enhanced bornyl acetate, 1,8-cineole, alpha- and beta thujones, while foliar fertilization increased bornyl acetate and camphor. The favorable effect of root colonization by Glomus intraradices was determined both on quantitative and qualitative pattern of sage essential oil. CONCLUSION: We conclude that inoculation with Glomus intraradices resulted in improved essential oil yield and quality, while combined application of foliar fertilizer and mycorrhizal fungi predominantly enhanced shoot biomass accumulation. PMID- 20355102 TI - Production of trans-free margarine stock by enzymatic interesterification of rice bran oil, palm stearin and coconut oil. AB - BACKGROUND: Trans-free interesterified fat was produced for possible usage as a spreadable margarine stock. Rice bran oil, palm stearin and coconut oil were used as substrates for lipase-catalyzed reaction. RESULTS: After interesterification, 137-150 g kg(-1) medium-chain fatty acid was incorporated into the triacylglycerol (TAG) of the interesterified fats. Solid fat contents at 25 degrees C were 15.5-34.2%, and slip melting point ranged from 27.5 to 34.3 degrees C. POP and PPP (beta-tending TAG) in palm stearin decreased after interesterification. X-ray diffraction analysis demonstrated that the interesterified fats contained mostly beta' polymorphic forms, which is a desirable property for margarines. CONCLUSIONS: The interesterified fats showed desirable physical properties and suitable crystal form (beta' polymorph) for possible use as a spreadable margarine stock. Therefore, our result suggested that the interesterified fat without trans fatty acid could be used as an alternative to partially hydrogenated fat. PMID- 20355103 TI - A new FT-IR method combined with multivariate analysis for the classification of vinegars from different raw materials and production processes. AB - BACKGROUND: Due to the diversity of vinegars on the market and the increase in demand, it is considered necessary to investigate and establish criteria for classifying them in order to obtain more information concerning their real origin. New spectroscopic techniques such us mid-infrared spectroscopy with Fourier transform (FT-IR) are capable of providing information in relation to these aspects. FT-IR combined with multivariate analysis has been used to classify vinegars according to the raw materials and production processes (with or without ageing in wood). Principal component analysis (PCA), partial least squares discriminant analysis regression (PLS-DA) and stepwise linear discriminant analysis (SLDA) were used. RESULTS: The results obtained have been compared to those achieved using different analytical parameters (polyphenolic content, organic acids and volatile compounds). SLDA and PLS-DA results show the ability of mid-FT-IR spectra to discriminate among vinegars from different raw materials and with or without ageing in wood, with correct classification percentages similar to those obtained using different analytical parameters. CONCLUSION: The discriminative ability combined with other advantages (e.g. rapid and non-destructive analysis, low cost) makes this new FT-IR method a promising tool for the classification and/or differentiation of vinegars. PMID- 20355104 TI - Effects of mild temperature conditions during dehydration procedures on saffron quality parameters. AB - BACKGROUND: The dehydration procedure is responsible for saffron sensorial properties: colour, taste and aroma. Changes in the compounds responsible for these characteristics have been studied when dehydration processes at high and low temperature are employed. However, the evolution of these changes at mild temperatures is not available in the current bibliography. In this paper the effect of different mild conditions (18-20 degrees C for 24 h, 40-50 degrees C for 75 min and 55 degrees C for 75 min) applied to 45 saffron samples with the same origin was investigated. RESULTS: Crocetin esters, the compounds responsible for saffron colour, increased their content with no significant differences from other processes when high temperatures (55 degrees C) were used, thus producing a noticeable increment in saffron colouring capability. Similar behaviour was obtained for picrocrocin, the compound responsible for saffron taste, with higher average content at the highest temperature (55 degrees C) but without significant differences with the inferior conditions (40-50 degrees C). However, more volatile compounds were generated, especially safranal,at higher temperatures, e.g. 55 degrees C, during the dehydration procedure. CONCLUSIONS: The results found support the idea for employing mild to high temperatures during the dehydration process of saffron. PMID- 20355105 TI - Stability of hydroperoxide lyase activity from Amaranthus tricolor (Amaranthus mangostanus L.) leaves: influence of selected additives. AB - BACKGROUND: Hydroperoxide lyase (HPL) has potential value for the flavour additive industry. Currently, the production and application of HPL suffer from stability problems. The objective of this study was to investigate the stabilisation of HPL preparation from Amaranthus tricolor leaves by the addition of selected chemical additives. RESULTS: Amaranthus tricolor leaves were identified as a particularly rich source of 13-HPL activity. The addition of 100 g L(-1) sucrose and trehalose to microsomal HPL prior to lyophilisation could retain nearly 100% enzymatic activity, compared to only 20% for the lyophilised control. The lyophilised microsomal HPL containing sucrose maintained full activity for even 40 days storage at -20 degrees C. For HPL solution, glycerol was effective for long-term stability at -20 degrees C. Moreover, poyols (sucrose and trehalose) and amino acid (glycine) enhanced the thermostability of HPL, while KCl and polyol mannitol decreased the thermostability of HPL. CONCLUSION: The flavour-producing enzyme HPL, found in the leaves of Amaranthus tricolor, was stabilised by the addition of chemical additives. PMID- 20355106 TI - Mechanical flower thinning improves the fruit quality of apples. AB - BACKGROUND: Apple 'Golden Delicious Reinders' and 'Gala Mondial' trees were mechanically blossom-thinned with 30-77 x g (300-480 rpm rotation) and 5 or 7.5 km h(-1) vehicle speed to improve fruit quality, minimise leaf damage, reduce hand and chemical thinning and to prevent or overcome alternate bearing; adjacent untreated or manually thinned apple trees served as controls. RESULTS: Mechanical thinning (43 x g, 360 rpm, 5-7.5 km h(-1)) had a positive effect on fruit size (15% larger), firmness (8.4 in Gala vs. 7.6 kg cm(-2) in the unthinned control), sweetness (124 vs. 117 g kg(-1) sugar in the control), contained the largest malic acid content (4 g kg(-1) vs. 3.4 g kg(-1) in the control) and 17% more anthocyanin (normalised anthocyanin index = 0.8 in Gala vs. 0.7 in the control); fruit of Golden and Gala showed additionally advanced starch breakdown and ripened earlier. CONCLUSIONS: Since increases in rotor speed, viz. centrifugal force, versus increases in the vehicle speed resulted in opposing effects, an integrated coefficient of thinning (ICT) was devised with optimum values of 10-40 (at 43 x g, 5-7.5 km h(-1)), where an ICT > 50 led to tree damage and ICT < 8 led to sub-optimum thinning efficacy. PMID- 20355107 TI - Structure and composition changes in the cell wall in relation to texture of shiitake mushrooms (Lentinula edodes) stored in modified atmosphere packaging. AB - BACKGROUND: Firmness in shiitake mushroom (Lentinula edodes) is an important textural attribute affecting consumer attitudes toward freshness and quality. In this study, the effects of modified atmosphere packaging (MAP) treatments on structure and composition changes in cell walls in relation to the texture of mushrooms were investigated. RESULTS: Shiitake mushrooms were packaged in low density polyethylene bags with no holes (M(0)), two microholes (M(1)), four macroholes (M(2)), stored at 4 degrees C for 16 days with non-wrapped mushrooms as control. Control mushrooms showed the highest firmness value due to significant increase of cellulose and chitin. All three MAP treatments reduced losses of protein and polysaccharides; the M(2) treatment can best preserve the original texture while mushrooms in M(0) became soft and deteriorated, possibly due to higher CO(2) accumulation, lower cellulose and chitin content. Transmission electron microscopy performed on caps at harvest and after 16 days indicated that disintegration of plasmalemma had been alleviated by M(2) treatment, leading to better preservation of the cell wall. CONCLUSION: Our results suggest that differences in firmness of shiitake mushrooms during storage may be due to differences in cellulose and chitin concentrations. M(2) treatment may be a useful way of maintaining shiitake mushrooms texture during storage at 4 degrees C. PMID- 20355108 TI - Mycorrhizal colonization and grain Cd concentration of field-grown durum wheat in response to tillage, preceding crop and phosphorus fertilization. AB - BACKGROUND: A 3-year field trial was conducted to investigate the effect of agricultural management practices including tillage, preceding crop and phosphate fertilization on root colonization by arbuscular mycorrhizal (AM) fungi and grain cadmium (Cd) concentration of durum wheat (Triticum turgidum L.). The relationship between grain Cd and soil and plant variables was explored to determine the primary factors affecting grain Cd concentration. RESULTS: Mycorrhizal colonization of the roots was reduced by conventional tillage or when the preceding crop was canola (Brassica napus L.), compared to minimum tillage or when the preceding crop was flax (Linum usitatissimum L.). In contrast, grain Cd was not consistently affected by any treatment. Grain Cd was generally below the maximum permissible concentration (MPC) of 100 microg Cd kg(-1) proposed by WHO. Grain Cd varied substantially from year to year, and could be predicted with 70% of variance accounted for by using the model: grain Cd concentration = - 321.9 + 44.5x ln(grain yield) + 0.26x soil DTPA-Cd + 182.5x soil electrical conductivity (EC)- 0.98x grain Zn concentration. CONCLUSIONS: These common agricultural management practices had no effect on grain Cd concentration in durum wheat though they impacted mycorrhizal colonization of roots. Grain yield and to a lesser extent soil conditions of EC and DTPA-Cd and grain Zn influenced grain Cd, whereas mycorrhizal colonization levels did not. PMID- 20355109 TI - Effects of micronization on the physico-chemical properties of peels of three root and tuber crops. AB - BACKGROUND: The aim of this study was to investigate the effect of micronization on the physicochemical properties of the peels of root and tuber crops, including yam (Dioscorea alata L.), taro (Colocasia esculenta L.) and sweet potato (Ipomea batatas L.). Two continuous milling sections, including hammer milling and ball milling, were applied to three samples to obtain micro-sized particles of root and tuber peels. The micronization by ball-milling treatment for 10 h was carried out to investigate the distribution of particle sizes and the changes in physiochemical properties. RESULTS: The results indicate that the peels of three crops appeared to be significantly decreased in particle size after 10 h of ball milling treatment. Moreover, the ball-milling treatments resulted in the redistribution of fiber components from insoluble fiber to soluble fiber. The micronization treatments decreased the bulk density but increased the solubility and water-holding capacities of the micronized peels. CONCLUSION: Our findings suggested that micronization treatments can improve functional properties of the fiber components of micronized peels, which provide a good source of dietary fiber in food applications. PMID- 20355110 TI - Capsaicin accumulation is related to nitrate content in placentas of habanero peppers (Capsicum chinense Jacq.). AB - BACKGROUND: The presence of capsaicin, the pungent principle of peppers, is restricted to the fruits of hot cultivars. This compound, which is produced in the fruits' placenta, requires 3 mol of nitrogen to be formed. Hence nitrogen availability may affect pepper pungency through its content in the fruit tissues. On the other hand, potassium may also affect pepper pungency given its positive effect on fruit development. In order to address this issue, plants of habanero pepper (Capsicum chinense Jacq.) were hydroponically cultured with various doses of nitrate and potassium and the contents of these ions and capsaicin were analyzed in the different fruit tissues. RESULTS: Treatments did not produce major effects on pod yield or size during the experimental period, and pepper pods from plants growing under low nitrate concentrations presented no significant differences in total nitrate content. However, lower nitrate, as well as low capsaicin contents, were found in the isolated placentas from peppers grown on the lowest nitrate doses. Variations in potassium availability resulted in differences in pod production per plant, but not in capsaicinoid accumulation. CONCLUSION: Under the assayed conditions, nitrate content in the placenta affects capsaicin synthesis. PMID- 20355111 TI - Effect of thermal treatments on phytochemicals in conventionally and organically grown berries. AB - BACKGROUND: Consumer demand for organic foods is increasing despite a lack of conclusive evidence of nutritional superiority of organically grown produce. The objective of this investigation was to evaluate the effects of thermal treatments on phytochemicals in conventionally and organically grown berries. Two cultivars of conventionally and organically grown red raspberries and blueberries were analysed for total anthocyanins, total and specific phenolic compounds and total antioxidant activity. Fresh berries were thermally processed into cans and juice/puree with and without blanching, and the changes in phytochemicals were monitored. RESULTS: Total anthocyanin and phenolic contents of berries were not influenced by the agricultural production system. Total antioxidant activity of berries was also not influenced by the production system, but antioxidant activity varied significantly between cultivars. After canning, total anthocyanins decreased by up to 44%, while phenolic contents and antioxidant activity of both berries generally increased by up to 50 and 53% respectively. The level of changes in phytochemicals during berry puree/juice processing was influenced by blanching and type of berries. CONCLUSION: Phenolic contents and antioxidant activities of berries increased while total anthocyanins decreased during canning. Blanching prior to puree/juice processing improved the retention of phytochemicals in blueberries. PMID- 20355112 TI - Suppression of blood glucose level by a new fermented tea obtained by tea-rolling processing of loquat (Eriobotrya japonica) and green tea leaves in disaccharide loaded Sprague-Dawley rats. AB - BACKGROUND: In the field of food science, much interest has been focused on the development of alternative medicinal foods with the ability to regulate excess blood glucose level (BGL) rise. The authors have successfully developed a new fermented tea product (LG tea) by co-fermentation of loquat (Eriobotrya japonica) leaf and summer-harvested green tea leaf. The objective of this study was to examine the acute suppression effect of LG tea on BGL rise in disaccharide-loaded Sprague-Dawley (SD) rats and to evaluate its possible usage as an antidiabetic functional food material. RESULTS: As a result of single oral administration of hot water extract of LG tea (50 mg kg(-1)) to maltose-loaded SD rats, BGL at 30 min was significantly decreased by 23.8% (P < 0.01) compared with the control. A corresponding reduction in serum insulin secretion was also observed. The ED(50) value of LG tea (50.7 mg kg(-1)) was estimated to be about 16-fold higher than that of the therapeutic drug acarbose (3.1 mg kg(-1)). CONCLUSION: No significant change in BGL was observed when sucrose or glucose was administered, suggesting that the suppression effect of LG tea was achieved by maltase inhibition, not by sucrase inhibition or glucose transport inhibition at the intestinal membrane. PMID- 20355113 TI - Silicon in beer and brewing. AB - BACKGROUND: It has been claimed that beer is one of the richest sources of silicon in the diet; however, little is known of the relationship between silicon content and beer style and the manner in which beer is produced. The purpose of this study was to measure silicon in a diversity of beers and ascertain the grist selection and brewing factors that impact the level of silicon obtained in beer. RESULTS: Commercial beers ranged from 6.4 to 56.5 mg L(-1) in silicon. Products derived from a grist of barley tended to contain more silicon than did those from a wheat-based grist, likely because of the high levels of silica in the retained husk layer of barley. Hops contain substantially more silicon than does grain, but quantitatively hops make a much smaller contribution than malt to the production of beer and therefore relatively less silicon in beer derives from them. During brewing the vast majority of the silicon remains with the spent grains; however, aggressive treatment during wort production in the brewhouse leads to increased extraction of silicon into wort and much of this survives into beer. CONCLUSION: It is confirmed that beer is a very rich source of silicon. PMID- 20355115 TI - Modelling the biological variance of the yellow aspect of Granny Smith apple colour. AB - BACKGROUND: The yellow aspect of colour is usually not considered for produce with a green-to-red or a green-to-yellow transition upon ripening. The magnitude of change is simply too small and, additionally, masked by a large variation. The colour of 'Granny Smith' apples, harvested from three orchards at two stages of maturity, was measured individually using the CIE L*a*b* system during storage in a regular atmosphere at three temperatures: 1, 4 and 10 degrees C. A model was developed based on a simplified mechanism, consisting of two consecutive reactions, to describe the development of the apple colour expressed as b* and L* values during storage. RESULTS: Monitoring individual apples made it possible to include and describe the biological variance of colour in batches of apples and to extract information on chilling injury, as a process active at 1 degrees C. All variations could be attributed to a single source related to the amount of yellowing compounds at the moment of harvest, indicating differences in state of maturity between individual apples. The obtained explained part (R(2) (adj)), using nonlinear mixed effects regression analysis was well over 90% for all data combined over more than 3000 observations. CONCLUSION: Orchard location had a slight effect on the mean initial colour value, indicating differences in development stage, most probably due to differences in assessing the harvest date. The magnitude of the variation in these colour values was, however, the same for all three orchards. The behaviour of the green colour aspect (a* value) has been reported separately, as this represents the major change in perceived colour. The changes in b* and L* values are rather small, while the biological variation between the individual fruit is at least of the same magnitude. The model presented here is, as far as known, the first model on b* and L* values for green-coloured products. Analysing b* and L* data using this model provides additional information with respect to the stage of maturity at harvest in a batch or for an orchard of Granny Smith apples. All the variation in the yellow colour aspects could be attributed exclusively to the initial level of yellow compounds. PMID- 20355114 TI - Effect of atmosphere composition on the quality of ready-to-use broccoli raab (Brassica rapa L.). AB - BACKGROUND: Many leafy brassicas are widely used for ready-to-use salads. Broccoli raab (Brassica rapa L.), also called turnip top, or rapini, is extensively cultivated in southern Italy. The edible portion is made up of the green, immature inflorescences and the stem with its most tender leaves. Recently, interest in this crop has increased among European consumers; moreover, a substantial increase in consumption could come from the ready-to-use product. RESULTS: The effects of four different atmosphere compositions (air, 3% O(2) in nitrogen, 3% O(2) + 10% CO(2) in air, and 10% CO(2) in air) on quality attributes of ready-to-use broccoli raab were studied. Controlled atmosphere affected appearance, composition, respiration rate, weight loss, and presence of off odours. Storage of broccoli raab florets under low oxygen conditions delayed post cutting deterioration during storage at 5 degrees C and preserved appearance and typical odour, up to 17 days. Moreover, respiration rate as well as loss of green colour, chlorophyll and vitamin C were also slowed down in this condition. Finally, in this study no effect of controlled atmosphere storage was found on total phenols content and antioxidant activity. CONCLUSION: Results showed that cold storage in 3% O(2) can be beneficial in order to maintain quality of ready to-use, broccoli raab for up to 17 days. PMID- 20355116 TI - Development of low-fat mayonnaise containing polysaccharide gums as functional ingredients. AB - BACKGROUND: The objective of this study was to develop a low-fat (LF) mayonnaise containing polysaccharide gums as functional ingredients. Xanthan gum (XG, 15 g kg(-1)), citrus fiber (CF, 100 g kg(-1)) and variable concentration of guar gum (GG) were used to formulate the optimum ratios of polysaccharide gums as fat replacers. The fat content in LF mayonnaise was reduced to 50% if compared with full-fat (FF) mayonnaise, and the products still maintained ideal rheological properties. RESULTS: The rheological parameters showed that there were no (P > 0.05) differences in yield stress, viscosity and flow behavior index between XG + 10 g kg(-1) GG, CF + 5 g kg(-1) GG and FF control. LF mayonnaises had lower caloric values and higher dietary fiber content than the FF counterpart. Scanning electron microscopy (SEM) micrographs illustrated that the network of aggregated droplets in LF treatments contained a large number of interspaced voids of varying dimensions. Furthermore, in a comparison of sensory evaluation of LF treatments with commercial and our FF mayonnaises, there were no (P > 0.05) differences in any sensory scores among XG + 10 g kg(-1) GG control. CONCLUSION: This study shows that XG + 10 g kg(-1) GG and CF + 5 g kg(-1) GG could be used in LF mayonnaise formulations based on its multiple functions on processing properties. PMID- 20355117 TI - Cadmium concentration in durum wheat grain (Triticum turgidum) as influenced by nitrogen rate, seeding date and soil type. AB - BACKGROUND: Cadmium (Cd) is a trace element that has been associated with various human health problems. Cd enters plants, either by direct absorption through leaves or by uptake from soils, allowing Cd into the food chain. Nitrogen (N) fertilizer management is important in optimizing crop yield and protein content of durum wheat, but may influence Cd availability and hence Cd concentration in crops, with the effects being strongly influenced by environmental conditions and crop cultivar. RESULTS: In field studies, Cd and protein concentration in durum wheat grain differed between cultivars and were strongly affected by N application, with only minor effects of N occurring on concentration and uptake of P and Zn. Protein content increased significantly with N application in five of six site-years, with the response being generally independent of cultivar and seeding data. Cd concentration also increased with N application in five of six seeding dates, with the response being greater in AC Melita than Arcola in three of the six site-years. There were large differences in Cd concentration from year to year and with seeding date, indicating a strong environmental influence. CONCLUSIONS: This study shows that different cultivars accumulate different levels of Cd in the grain and that seeding date and nitrogen fertilizer management can influence grain Cd concentration, with the magnitude of effects varying with environmental factors. In the future we may be able to manipulate management practices to optimize protein concentration and minimize Cd concentration in durum wheat, which could help to address the health and safety concerns of consumers. PMID- 20355118 TI - Scirpusin A, a hydroxystilbene dimer from Xinjiang wine grape, acts as an effective singlet oxygen quencher and DNA damage protector. AB - BACKGROUND: Grapes and red wines are rich sources of phenolic compounds such as anthocyanins, catechins, flavonols and stilbenes, most of which are potent antioxidants showing cardioprotective properties. We first isolated scirpusin A, a hydroxystilbene dimer, from a wine grape of Xinjiang, and studied its antioxidant activity. RESULTS: Reactive oxygen species scavenging effects and the protection against reactive singlet oxygen-induced DNA damage of scirpusin A have been investigated in our experiments. The concentration of scirpusin A required to inhibit 50% of (1)O(2) generation was 17 micromol L(-1), while addition of scirpusin A at 140 micromol L(-1) caused complete inhibition. Further kinetic study revealed that the reaction of Scirpusin A with singlet oxygen has an extremely high rate constant (k(a) = 4.68 x 10(9) L mol(-1) s(-1)). Scirpusin A (140 micromol L(-1)) exhibited significant inhibition effects on pBR322 DNA breakage. However, scavenging effects of scirpusin A on superoxide anion O(2) (* ) and hydroxyl radical .OH were not potent as the inhibitor rates at a concentration of 1400 micromol L(-1) were 28.83% and 19.5%, respectively. CONCLUSION: The present study shows that scirpusin A is a selective quencher of singlet oxygen and a protector against reactive singlet oxygen-induced pBR322 DNA damage at very low concentrations. PMID- 20355119 TI - The influence of plant polyphenols on lipolysis and biohydrogenation in dried forages at different phenological stages: in vitro study. AB - BACKGROUND: It is known that forage legumes show a higher transfer efficiency of polyunsaturated fatty acids (PUFA) to ruminant dairy products in comparison with grasses. Legumes are usually characterised by moderate levels of plant secondary metabolites, which can have an effect on lipolysis and biohydrogenation in the rumen. An in vitro study was carried out to compare two species with different plant phenol compositions, Vicia sativa (VS, common vetch, cv. Jose) and Trifolium incarnatum (TI, crimson clover, cv. Viterbo) cut at the vegetative (Veg) and reproductive (Rep) stages, on lipolysis and PUFA biohydrogenation in the rumen. RESULTS: The study showed that forage species and phenological stage affected the levels of bound phenols (BP) and tannic polyphenols (TP). VS was characterised by a higher level of TP than TI at both Veg and Rep stages, whereas BP levels were low in both forages. BP and TP had a negative effect on lipolysis and biohydrogenation, but TP showed a greater negative correlation than BP for both forages. CONCLUSION: These results showed that lipolysis and biohydrogenation of PUFA could be affected by plant phenols, particularly TP. PMID- 20355120 TI - Fumonisin detection and analysis of potential fumonisin-producing Fusarium spp. in asparagus (Asparagus officinalis L.) in Zhejiang Province of China. AB - BACKGROUND: Fumonisins are mycotoxins produced by a number of Fusarium species, including several pathogens of asparagus plants. China is one of the largest asparagus producers in the world. In this study, we analysed the contamination of fumonisins and fumonisin-producing fungi in asparagus spear samples from Zhejiang Province, the major asparagus production province in China. RESULTS: The asparagus did not contain a detectable level of fumonisins. However, the recovery of Fusarium in asparagus was 72.7%, including F. proliferatum (40.9%), F. oxysporum (22.7%), F. acuminatum (4.55%) and F. equesti (4.55%). A multiplex PCR targeting the internal transcribed spacer sequence (ITS), translation elongation factor 1-alpha (TEF), and key biosynthetic genes FUM1 and FUM8, was used to simultaneously determine the identity and the biosynthetic ability of the fungal isolates. Fungal isolates containing the FUM genes also produced fumonisins in cultures, ranging from 28 to 4204 microg g(-1). F. proliferatum was the only fumonisin-producing Fusarium species in asparagus. CONCLUSION: Although no fumonisin contamination was detected in asparagus in the current survey, we found that the majority of samples contained Fusarium spp. Because F. proliferatum is a high fumonisin-producing species, potential health risks for human consumption of asparagus exist, if the appropriate environmental conditions are present for this fungus. PMID- 20355121 TI - Effects of the beta-glycosidase reaction on bio-conversion of isoflavones and quality during tofu processing. AB - BACKGROUND: Isoflavones are the most common group of phytoestrogens which are present in significantly large amounts in soybean and soy products such as tofu. Isoflavones occur naturally in glycoside forms having lower bioavailability than their aglycone forms. beta-Glycosidase acts as a bio-catalyst for the conversion of isoflavone glycosides to isoflavone aglycones, raising the bioavailability of isoflavones; therefore, it can be used to improve the quality of tofu. We need to establish process conditions for the optimal outcome of the enzyme reaction in tofu. RESULTS: By using the beta-glycosidase (0.02% w/v) reaction at 55 degrees C for 30 min, a maximum 84.5% conversion of isoflavone glycoside to isoflavone aglycone was obtained. The enzyme reaction caused no significant effects on the sensory acceptability of soft tofu. The hardness of enzyme-treated hard tofu increased with the coagulant amount whereas prolonged heating resulted in decrease of hardness. Incorporation of enzyme reaction before the coagulation process during soft tofu processing provided a sufficient bio-conversion of isoflavones at optimal conditions. CONCLUSION: beta-Glycosidase can be effectively used for the bioconversion of isoflavones in soft tofu manufacturing process at optimal reaction conditions before the onset of coagulation process. PMID- 20355122 TI - Effect of malting conditions and quality characteristics of malt and roasted malt extract from 'acha' grains (Digitaria exilis Stapf). AB - BACKGROUND: Considering the importance of malting and roasting on the quality of 'acha' beverages, a study was conducted to find optimum conditions for malting and the production of a high-quality roasted extract that could be used for an 'acha' beverage. RESULTS: The data obtained were analysed using response surface methodology. The results revealed that the most significant (P < 0.05) malting factors that affect the response variables were the linear terms of germination time and drying temperature. However, for the extract production, the linear term of roasting temperature was the most significant (P < 0.05) factor. The quadratic and interaction terms exhibited significant (P < 0.05) effect in all cases apart from the flavour. CONCLUSION: The overall optimum regions were established at 28 h of germination time, 55 degrees C drying temperature and 5.0% moisture content for the malting conditions while for the extract production, a roasting temperature of 210 degrees C, extraction temperature of 70 degrees C and extraction duration of 20 min were established. PMID- 20355123 TI - Influence of colour type and previous cultivation on secondary metabolites in hypocotyls and leaves of maca (Lepidium meyenii Walpers). AB - BACKGROUND: Maca is an Andean crop of the Brassicaceae family which is mainly known for its fertility-enhancing properties following consumption. The hypocotyls display various colours ranging from white to black. Each colour has different biological effects. The aim of this study was to analyse the concentrations of major secondary metabolites in hypocotyls and leaves of maca in a controlled planting experiment in the Peruvian Andes at 4130 m above sea level. The effects of colour type and of previous cultivation of the field were examined. RESULTS: In the hypocotyls, the colour type effect was significant for most secondary metabolites; exceptions were beta-sitosterol and campesterol. The lead-coloured, yellow and violet maca hypocotyls were rich in glucosinolates, macaene and macamides, respectively. Previous cultivation affected macaene, campesterol and indole glucosinolate concentrations. Effects on metabolite concentrations in the leaves were minor. Hypocotyls were richer in macaene, macamides and glucosinolates than were leaves, and were poorer in beta-sitosterol and total phenols. CONCLUSION: Colour type has to be considered in maca production, as colour associates with variations in concentrations of distinct bioactive metabolites. Leaves may be interesting for animal nutrition purposes as they contain essentially the same secondary metabolites as the hypocotyls but in clearly lower concentrations. PMID- 20355125 TI - Direct competitive enzyme-linked immunosorbent assay (ELISA) for rapid screening of anisakid larvae in seafood. AB - BACKGROUND: Anisakid larvae are one of the most important pathogenic parasites in marine products; however, simple and rapid analytical techniques for them are still very limited. In this research, based on specific rabbit polyclonal antibodies which were raised against crude extracts of Anisakis larvae, purified by protein A affinity chromatography and labeled with horseradish peroxidase, a direct competitive enzyme-linked immunosorbent assay (ELISA) was developed and validated for detection of anisakid larvae in seafood. RESULTS: The established method exhibited a broad selectivity to Anisakis larvae and Pseudoterranova larvae, and the lowest detection limit to them was estimated to be about 5 parasites kg(-1) in food matrix. Using Pseudopleuronectes yokohamae, Scomberomorus niphonius and Ommastrephes bartrami as samples and within spiking concentrations from 20 to 100 larvae kg(-1), the determination recovery for Anisakis larvae and Pseudoterranova larvae ranged from 77.8% to 107.0%, with relative standard deviations all less than 20%. CONCLUSION: The results allowed us to suggest the established direct competitive ELISA as an effective analytical tool for fast screening of anisakid larvae in sea foods. PMID- 20355124 TI - Microbial inhibitory and radical scavenging activities of cold-pressed terpeneless Valencia orange (Citrus sinensis) oil in different dispersing agents. AB - BACKGROUND: Due to their low solubility in water, oil-based bioactive compounds require dispersion in a surface-active agent or appropriate solvents to ensure maximum contact with microorganisms. These combinations, however, may change their physical and/or chemical characteristics and consequently alter the desired functionality. The objective of this study was to determine the impact of selected dispersing agents, ethanol, dimethyl sulfoxide (DMSO), and Tween-80, on cold-pressed terpeneless (CPT) Valencia orange oil to function as a free radical scavenger and an antimicrobial food additive. RESULTS: When dissolved in ethanol or DMSO, the orange oil fraction had similar minimum inhibitory concentrations (MIC) for Listeria monocytogenes ATCC 19 115 (0.3% and 0.25% v/v respectively), which were significantly lower (P 0.05) for all acceptance test attributes. Overall acceptability was found to be highly and negatively correlated for hardness, fracturability and cohesiveness (R(2) > 0.90). Principal component analysis showed that the taste attribute of cookies and the % solid fat content of margarine at 35 degrees C highly influenced the overall quality of the cookies. CONCLUSION: Cookies made from MLCT-enriched margarines were not successfully produced. However, the findings obtained provide new perspectives in the production of low-calorie bakery fat. PMID- 20355134 TI - Predicting degradability parameters of diets for ruminants using regressions on chemical components. AB - BACKGROUND: Dry matter degradability (DMD) parameters (a, b and c in the Orskov and McDonald model) are usually determined by the nylon bag technique. The aim of this study was to estimate DMD parameters of ruminant mixed diets, which are in general unavailable, through multiple linear regressions on their chemical composition (ash, crude protein, neutral detergent fibre (NDF), acid detergent fibre (ADF) and acid detergent lignin (ADL)). The regressions were based on data from 77 feeds. RESULTS: The prediction model for a was reduced to a simple linear regression on NDF (adjusted R(2) = 0.727, F test P < 0.001). A regression model for b was obtained with ADL as the sole predictor (adjusted R(2) = 0.691, P < 0.001). The model's upper asymptote (a + b) was predicted from ADL, NDF and ash (adjusted R(2) = 0.908, P < 0.001). Modelling c proved more difficult (adjusted R(2) with all five predictors = 0.481, P < 0.001). CONCLUSION: Regressing model parameters on feed chemical composition is a promising method for estimating the degradability of mixed diets, providing an alternative to invasive and expensive laboratory techniques. PMID- 20355135 TI - Norwegian-grown Jerusalem artichoke (Helianthus tuberosus L.): morphology and content of sugars and fructo-oligosaccharides in stems and tubers. AB - BACKGROUND: Two field trials growing Jerusalem artichoke (Helianthus tuberosus L.) are discussed. Twenty genetic variants were compared in order to find genotypes suitable for Norwegian production. A second trial investigated the above-ground part of early and late variants. RESULTS: The highest yield (28.7 t ha(-1)) and highest amount of tubers per plant was obtained in early variants, e.g. the white Tysnes gave 1.72 kg tubers plant(-1). Early variants had a markedly lower portion of smooth tubers. Late variants gave the most preferable tuber shape, but low yield. Only a weak correlation was found between dry matter content and total content of fructo-oligosaccharides (FOS) (r = 0.255) in the tubers. The mean content of FOS including sucrose through all variants was found to be 116 g kg(-1) fresh weight (FW) or 550 g kg(-1) dry weight (DW). The average chain length of FOS in the tubers was found to be DP3.9. There was no difference in tuber FOS content between early and late variants. The highest above-ground amount biomass was found for the late variants when harvested in September. The content of soluble carbohydrates was found to be highest in stalks in August (sucrose and FOS major compounds). CONCLUSION: Early variants give the highest tuber yield under Norwegian growing conditions. Late variants give highest above ground biomass. PMID- 20355136 TI - Effect of municipal solid waste compost and sewage sludge use on wheat (Triticum durum): growth, heavy metal accumulation, and antioxidant activity. AB - BACKGROUND: Inappropriate utilisation of biosolids may adversely impact agrosystem productivity. Here, we address the response of wheat (Triticum durum) to different doses (0, 40, 100, 200 and 300 t ha(-1)) of either municipal solid waste (MSW) compost or sewage sludge in a greenhouse pot experiment. Plant growth, heavy metal uptake, and antioxidant activity were considered. RESULTS: Biomass production of treated plants was significantly enhanced at 40 t ha(-1) and 100 t ha(-1) of MSW compost (+48% and +78% relative to the control, respectively). At the same doses of sewage sludge, the increase was only 18%. Higher doses of both biosolids restricted significantly the plant growth, in concomitance with the significant accumulation of heavy metals (Ni2+, Pb2+, Cu2+ and Zn2+), especially in leaves. Leaf activities of antioxidant enzymes (ascorbate peroxidase, glutathione reductase, catalase and superoxide dismutase) were unchanged at 40 t ha(-1) MSW compost or sewage sludge, but were significantly stimulated at higher doses (200-300 t ha(-1)), together with higher leaf concentration of reduced glutathione. CONCLUSION: This preliminary study suggests that a MSW supply at moderate doses (100 t ha(-1)) could be highly beneficial for wheat productivity. PMID- 20355137 TI - Aqua regia extractable selenium concentrations of some Scottish topsoils measured by ICP-MS and the relationship with mineral and organic soil components. AB - BACKGROUND: To provide information concerning the geographical distribution of selenium (Se) in the soils of Scotland, we analysed 47 arable soils selected on the basis of their parent rock, which were expected to have relatively high, low or unclassified Se concentrations. To investigate relationships between the actual minerals in the soils and the aqua regia extractable Se concentration of the soil, soil minerals were quantified by X-ray diffraction. RESULTS: The aqua regia extractable Se concentrations of the soils were between 0.19 and 1.46 mg kg(-1). No simple correlation between the aqua regia extractable Se concentrations of the soil and the parent rock classification estimated by soil survey was evident. Partial least squares analysis revealed that the aqua regia extractable Se concentration of the soils was positively related to loss on ignition (LOI) or C concentration and negatively related to the K-feldspar concentration, with other minerals being less important. CONCLUSION: The Se concentration of arable topsoils from Scotland is more related to LOI or carbon concentration, with parent material being less important. PMID- 20355138 TI - Effect of organic production and fertilizer variables on the sensory properties of pac choi (Brassica rapa var. Mei Qing Choi) and tomato (Solanum lycopersicum var. Bush Celebrity). AB - BACKGROUND: The increased popularity of organic production has amplified the need for research that will help in understanding how this production system affects the final quality of vegetables. The effects of organic and conventional production on the sensory characteristics of pac choi (often called bok choy) and tomato were studied. Samples were grown in high tunnel and field environments at the Kansas State University Horticulture Research Center located in Olathe, Kansas. Highly trained descriptive panelists from the Sensory Analysis Center at Kansas State University used previously developed flavor lexicons for tomatoes and leafy greens to evaluate the samples. RESULTS: ANOVA at a 95% confidence level was used to detect significant differences between treatments for individual attributes. Crispness, green-grassy/leafy, piney, and pungent attributes were normally higher in conventional pac choi only for the field samples. Pac choi grown in high tunnels showed slight differences only at individual amounts of fertilizer. Organic tomatoes grown in the field were generally juicier and less mealy compared to conventionally grown tomatoes. In the high tunnel, organic tomatoes were generally stronger in the characteristic tomato aroma. However, all differences generally were very small. CONCLUSION: It can be concluded that organic and conventional production systems do not create major sensory differences in the vegetables evaluated. The few differences that do exist are so small they may not be of practical importance. PMID- 20355139 TI - Impact of postharvest methyl jasmonate treatment on the volatile composition and flavonol content of strawberries. AB - BACKGROUND: Although strawberry aroma is very complex, certain compounds have been described as main contributors, i.e. furanones, aldehydes, alcohols, sulfur compounds and particularly methyl and ethyl esters. In addition, strawberries possess potent antioxidant activity because of their high content of phenolic compounds. Among them, flavonols are highlighted as important antioxidant compounds in strawberry. The objective of this study was to assess the effect of methyl jasmonate (MJ) on the composition of the major contributors to aroma and on the content of certain flavonols in strawberry fruits. RESULTS: The levels of all studied volatile compounds were significantly affected by MJ treatment, though the individual effect differed according to the specific compound considered. Most of them increased significantly (P < 0.05), except methyl butanoate, which always showed higher levels in untreated strawberries. In contrast to aroma compounds, the change in the concentration of flavonols (i.e. myricetin, quercetin and kaempferol) was not significant in MJ-treated strawberries. Considering the health-promoting activity of these compounds, further investigations on the experimental conditions related to the treatment are required to control flavonol bioformation by means of MJ. CONCLUSION: The exogenous application of MJ vapour to strawberry enhances, in general, the production of the most relevant aroma-active compounds. On the contrary, MJ treatment does not appear to influence the levels of myricetin, quercetin and kaempferol. Thus postharvest MJ treatment is proposed as an approach to obtain improved strawberry fruits in terms of sensory quality and health-promoting properties. PMID- 20355140 TI - Effects of wax coatings and postharvest storage on sensory quality and aroma volatile composition of 'Mor' mandarins. AB - BACKGROUND: Mandarins suffer from accumulation of off-flavours after harvest. In this study the sensory quality and aroma profile composition of homogenised segments of untreated (control) and wax-coated 'Mor' mandarins after 7 days at 20 degrees C or 3 or 6 weeks of cold storage at 5 degrees C were examined. RESULTS: Fruit taste score decreased during storage and following wax coating, and this was attributed to decreases in sourness and mandarin flavour and accumulation of off-flavours. Aroma profiling identified 31 volatiles that decreased by at least 50% during storage and after waxing and thus may be involved in the observed flavour loss. In contrast, 13 volatiles, mostly belonging to ethanol fermentation and fatty acid and amino acid catabolism pathways, significantly increased at least twofold and probably contributed to off-flavour enhancement. CONCLUSION: The results showed that after harvest there was a progressive decrease in sensory quality of 'Mor' mandarins. It is proposed that observed decreases in contents of sesqui- and monoterpenes and short-chain oxygenated fatty acids may contribute to the decrease in mandarin flavour, whereas increases in the contents of ethanol fermentation metabolites and derivates of fatty acid and amino acid catabolism are most likely involved in causing the enhanced sensation of off-flavours. PMID- 20355141 TI - Fruit physical, chemical and aromatic attributes of early, intermediate and late apricot cultivars. AB - BACKGROUND: In order to reach good fruit quality, apricots require a balance of sugars and acids as well as a strong apricot aroma. In this study, fruit quality of early, intermediate and late apricot cultivars was evaluated by measuring physical, chemical and olfactory attributes. Multivariate analysis of quality and aroma attributes was used to identify groups of similar cultivars and association with ripening season. RESULTS: Physical, chemical and aromatic attributes showed great variation among cultivars but no relation to ripening season. Aromatic profiles (34 volatiles) of fruit tissues indicated qualitative and quantitative differences among cultivars. Ninfa and Mandorlon were richest in aroma, with a prevailing fruity component; Goldrich and Orange Red were also highly aromatic, with all odour components well represented; Pinkot, Alba and Pellecchiella were lowest in aroma, with a prevailing grassy component. Linear functions including five volatiles (concentrations) and fruit diameter or six aromatic compounds (odour units) and peel colour were found to discriminate cultivars by ripening season. Principal component analysis individuated three groups of cultivars: Ninfa and Mandorlon with sweet and fruity-flavoured fruits; Bulida, Alba, Goldrich, Ouardy and Silvercot with large, acidic and well-coloured fruits; and Fracasso, Pellecchiella, Palummella and Pinkot with small and floral/grassy flavoured fruits. CONCLUSION: In apricot, detailed analysis of the aromatic profile may represent an efficient tool for classification of genotypes by ripening season, and volatiles with relevant odour contribution may serve as quality markers for selecting towards an extended ripening season of best quality apricots. PMID- 20355142 TI - Sensitive enzyme-linked immunosorbent assay and rapid one-step immunochromatographic strip for fumonisin B1 in grain-based food and feed samples. AB - BACKGROUND: Maize contaminated with mycotoxin fumonisin B1 poses a global threat to agricultural production. In this study, polyclonal antibodies (pAb) specific to fumonisin B1 were generated from rabbits immunised with fumonisin B1-keyhole limpet haemocyanin (KLH). These antibodies were used to establish a sensitive competitive direct enzyme-linked immunosorbent assay (cdELISA) and gold nanoparticle immunochromatographic strip for detecting fumonisin B1 levels in maize-based foods and feeds. RESULTS: In cdELISA, fumonisins B1, B2 and B3 at concentrations of 0.42, 0.58 and 81.5 ng mL(-1) respectively caused 50% inhibition (IC(50)) of binding of fumonisin B1-horseradish peroxidase (HRP) to the antibodies. Effective on-site detection of fumonisin B1 was achieved by developing a rapid and sensitive pAb-based gold nanoparticle immunochromatographic strip. This strip had a detection limit of 5 ng mL(-1) for fumonisin B1 in maize-based samples. Additionally, the whole analytical process could be completed within 10 min. Close examination of 15 maize-based samples by cdELISA revealed that 11 were fumonisin-positive, with a mean concentration of 435 +/- 20.1 ng g(-1). These results correlated well with those obtained by immunochromatographic strip. CONCLUSION: Both cdELISA and immunochromatographic strip methods established in this study are sensitive for rapid detection of fumonisins in agricultural commodities. PMID- 20355143 TI - Purification and biochemical characterisation of a novel glutamate decarboxylase from rice bran. AB - BACKGROUND: Glutamate decarboxylase (GAD) is a useful enzyme whose main function is to catalyse the irreversible alpha-decarboxylation of L-glutamate to produce gamma-aminobutyric acid. The cheap and abundant rice-processing by-product rice bran contains a high amount of GAD, the purification and characterisation of which have not yet been reported. In this study, research on rice bran GAD was initiated. RESULTS: Rice bran GAD was purified to homogeneity via a combined purification protocol of ammonium sulfate fractionation, ion exchange chromatography and two gel filtrations, with a purification fold of 128.6 and an activity recovery of 21.3%. The enzyme was active at pH 5.5 and 40 degrees C and retained 80% of its original activity in the pH range 5-9 and the temperature range 30-50 degrees C. GAD activity was significantly enhanced in the presence of Ca2+ but strongly inhibited by Ag+, Hg2+, sodium dodecyl sulfate and CH3COOH. Kinetic determination of the apparent K(m) for L-glutamate and pyridoxal 5' phosphate gave values of 27.4 mmol L(-1) and 1.16 micromol L(-1) respectively. CONCLUSION: Considering that rice bran is cheap and commercially available and that rice bran GAD is relatively stable, the development of cost-effective rice bran GAD-related functional foods would seem to be feasible. PMID- 20355144 TI - Purification and characterization of parvalbumins from silver carp (Hypophthalmichthy molitrix). AB - BACKGROUND: As the largest producer and consumer of freshwater fish in the world, many people suffer from allergy for consuming freshwater fish in China. However, the allergen profiles of freshwater fish are rarely known. RESULTS: Parvalbumins (PVs) from the white muscle of silver carp (Hypophthalmichthy molitrix) were purified by ammonium sulfate fractionation and column chromatography including DEAE-Sepharose and Superdex 75. Three PV isoforms-PV-I, PV-II, and PV-III-were obtained and their molecular masses as estimated by tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 12, 11, and 14 kDa, respectively. All the PVs could be detected by anti-frog PV monoclonal antibody. PV-I and PV-II were quite possibly glycoproteins, while PV-III was not glycosylated, as analyzed by periodic acid-Schiff (PAS) staining. Thermal stability revealed that PV-I and PV-II easily formed polymers, while these proteins were stable in a pH range of 4.0-10.0. A PV gene encoding 110 amino acid residues was cloned and it revealed high identity with PVs from other species of fish. CONCLUSION: Three isotypes of PV were purified to homogeneity and one distinct PV gene was cloned in silver carp white muscle. PMID- 20355145 TI - Chemical profiling of Portuguese Pinus pinea L. nuts. AB - BACKGROUND: The first detailed chemical characterisation of Portuguese pine nut (Pinus pinea L.) is reported concerning proximate composition, fatty acid, mineral and vitamin contents. RESULTS: Based on the analysis of 27 different populations, pine nuts were characterised by high contents of fat (47.7 g per 100 g dry matter (DM)), protein (33.8 g per 100 g DM) and phosphorus (1130 mg per 100 g DM) and low contents of moisture (5.9 g per 100 g DM) and starch (3.5 g per 100 g DM). They were also found to be a good source of zinc, iron and manganese. CONCLUSION: Mineral composition seemed to be most prone to variation, suggesting its potentially useful role in discriminating Mediterranean pine nuts. A significant variability was found in the nut composition of Portuguese P. pinea populations. PMID- 20355146 TI - Cholesterol and lipid oxidation in raw and pan-fried minced beef stored under aerobic packaging. AB - BACKGROUND: The type of packaging atmosphere has been reported as a technological factor that consistently affects the quality of lipid fraction in meat. Oxidation of cholesterol and lipids was evaluated before and after pan frying in commercial refrigerated minced beef stored under aerobic atmosphere for 1 and 8 days. RESULTS: In raw beef, cholesterol and lipid oxidation developed at a slow rate. Cholesterol oxidation products (COPs) did not significantly vary (approximately 8 microg COPs g(-1) of fat) over 8 days, while in the same period thiobarbituric acid reactive substances (TBARS) less than doubled (from 0.7 to 1.2 malondialdehyde equivalents kg(-1) of muscle). Pan frying did not influence the oxidative degree in the fresh product but consistently catalyzed cholesterol oxidation in stored beef. A significant increase was assessed in beef at the end of storage: from 8.6 to 30.0 microg COPs g(-1) of fat in raw and cooked beef, respectively. CONCLUSION: Aerobic packaging did not appear as a pro-oxidant factor in fresh minced beef with a good oxidative quality during a short period of refrigerated storage. PMID- 20355147 TI - Comparative post-harvest behaviour of traditional and virus-resistant Muchamiel tomatoes. AB - BACKGROUND: Nowadays, organoleptic quality is the primary objective for almost all tomato breeding programmes. In this study, post-harvest behaviour of a breeding line with genetic resistance to important viruses (tomato mosaic virus, tomato spotted wilt virus and tomato yellow leaf curl virus) has been compared with the original traditional landrace (Muchamiel). The breeding line has been obtained by backcrossing, introgressing three resistance genes but aiming to keep the quality characteristics of the traditional variety. Tomatoes were picked at random and stored at 10 degrees C for 13 days. Quality analyses were made in both tomato samples: weight loss, colour, respiration rate, ethylene production, maturity index, instrumental hardness and sensory evaluation with trained panel. RESULTS: Fruits of the breeding line were characterized by higher hardness even with a higher maturity index. Results of sensory tests were in agreement with instrumental measurements. Organoleptic quality of Muchamiel virus-resistant tomatoes was at least as high as that of traditional tomatoes, reaching the best scores in odour and aroma at the 13th storage day. CONCLUSION: Although a long time has been required to develop the breeding line, results indicate that organoleptic fruit quality has been recovered through backcrossing, confirming the success of the breeding programme. PMID- 20355148 TI - Biochemical, biological and histological evaluation of some culinary and medicinal herbs grown under greenhouse and field conditions. AB - BACKGROUND: Increasing evidence supports the potential health benefits of herbal extracts displaying antioxidant, anti-inflammatory and antitumour activities. Environment can have a pronounced effect on phenolic content and antioxidant capacity. The objectives of this study were to evaluate the total phenolic contents and antioxidant capacities of five different herbs grown under greenhouse and field conditions and to assess their potential anti-inflammatory effects. RESULTS: High total polyphenolic (TPP) content (measured by the Folin Ciocalteu reagent method) and high Trolox equivalent antioxidant capacity (TEAC) were observed in all herbs evaluated. Leaves from thyme, sage, spearmint and peppermint grown in the greenhouse showed significantly higher TPP content and TEAC than those grown under field conditions, with a threefold difference being observed in peppermint. Rosemary, spearmint and peppermint extracts showed stronger inhibition of cyclooxygenase COX-2 than of COX-1. CONCLUSION: The results show that producing herbs under greenhouse conditions can improve their biological activities by increasing TPP contents and antioxidant capacities. The selective inhibition of COX-2 activity by rosemary, spearmint and peppermint suggests that they may be useful as anti-inflammatory agents with fewer side effects than regular non-steroidal drugs. PMID- 20355149 TI - An FTIR study of the induction and release of kiwifruit buds from dormancy. AB - BACKGROUND: Many deciduous, perennial fruit crops require winter chilling for adequate budbreak and flowering. Recent research has shown that changes in sugar and amino acid profiles are associated with the release of buds from dormancy. This paper uses FTIR spectrometry to provide an alternative mechanism for tracking metabolic changes in the meristems of kiwifruit buds during winter dormancy. The results suggest that the application of multivariate analysis to FTIR spectra has the potential to be a reliable and fast method for detecting structural and compositional changes in fruit crops. RESULTS: Ten wave numbers of the FTIR spectra are used to calculate a bud development function. This function has been validated using data from two seasons and four orchards, and by monitoring the effects of hydrogen cyanamide application, sugar concentrations and soil temperatures on this function. These wave numbers appear to be associated with carbohydrate, pectin and cellulose levels in the meristems. CONCLUSION: It is expected that this FTIR signature can be used to advance our understanding of the influence of the various environmental and physiological factors on the breaking of bud dormancy and shoot outgrowth, including the optimum timing and concentrations of applications of budbreak regulators, such as hydrogen cyanamide. PMID- 20355150 TI - Sensory properties and consumer acceptance of sweet tamarind varieties grown in Thailand. AB - BACKGROUND: Sweet tamarind is a major edible fruit and flavoring ingredient particularly in south-east and southern Asia. Little research has focused on the fruit and almost nothing is known of its particular sensory properties. The aims of this research were to develop a lexicon for describing sweet tamarind, to compare varieties grown in Thailand, determine if orchard impacts sensory properties, and determine consumer acceptance of the varieties. RESULTS: A descriptive sensory lexicon of 25 terms was developed and six varieties were grouped into three clusters based on their sensory properties. The clusters appear to represent varieties that differ in their dark fruity notes and firm, fibrous texture. Generally, the orchard in which the plants were grown had little effect on sensory properties. In general, Sithong was liked by consumers along with Kunthee and Pragaithong. Intapalum was liked less but one small segment of consumers disliked Sithong and liked the Intapalum variety more. CONCLUSIONS: This research provides a foundation for further sensory and consumer research on sweet tamarind varieties by providing the initial data on the sensory properties of sweet tamarind, a lexicon that can be used for future research, and information on the consumer acceptance of tamarind varieties. PMID- 20355151 TI - Quality of fresh-cut baby spinach grown under a floating trays system as affected by nitrogen fertilisation and innovative packaging treatments. AB - BACKGROUND: Alternative techniques for cultivation of leafy vegetables such as a floating tray system and unconventional gas mixtures for post-harvest active modified atmosphere packaging (MAP) could be of interest in the minimally processed vegetable industry. RESULTS: The combined effect of three pre-harvest fertilisation doses (8, 12 or 16 mmol N L(-1)) and three post-harvest MAP conditions (passive, super-atmospheric or N2O-enriched) on the main quality attributes of fresh-cut baby spinach leaves throughout 10 days at 5 degrees C was studied. After 8 days of shelf life, spinach leaves fertilised with 8 and 16 mmol N L(-1) and stored under N2O-enriched MAP showed the lowest microbial growth, with good sensory quality. Such combined treatments also preserved the total antioxidant capacity sampled at harvest (8 g ascorbic acid equivalent antioxidant capacity kg(-1) f.w.). A decrease of 10-20% in total vitamin C content regardless of N fertilisation and packaging treatment was found during shelf life. Total phenolics content at harvest was 2 g gallic acid equivalents kg(-1) f.w., which was slightly decreased or preserved during shelf life while total chlorophylls were preserved for all treatments assayed around 550 mg kg(-1) f.w. CONCLUSION: No clear effect of fertilisation doses was observed during post-harvest storage on overall quality of fresh-cut baby spinach leaves, while N2O-enriched atmospheres seems to be a promising alternative to passive MAP for extending shelf life. PMID- 20355152 TI - Launch editorial. PMID- 20355153 TI - Annual banned-substance review: the Prohibited List 2008-analytical approaches in human sports drug testing. AB - The list of prohibited substances and methods of doping issued by the World Anti Doping Agency is updated and modified annually based on most recent developments and scientific data. Compounds and methods are maintained, added, or removed from the list, or they are placed in so-called monitoring programmes that have been established to obtain reliable data on the prevalence of particular substances and methods in- and/or out-of-competition. Consequently, doping control laboratories continuously update, modify and optimize existing screening and confirmation assays to ensure utmost comprehensiveness in detecting the prohibited and monitored substances as well as chemically and pharmacologically related analogs. The annual banned-substance review for human sports drug testing critically summarizes recent innovations in analytical approaches supporting the detection of established and newly outlawed substances and methods of doping. Literature from January 2007 through September 2008 as indexed in Medline and Web of Science was screened and articles on detection methods for substances and methods of doping in humans were compiled according to the 2008 Prohibited List of the World Anti-Doping Agency. Few new approaches were presented for individual doping agents and the majority of reports demonstrated new options for increasing the comprehensiveness of existing doping control assays. In addition, new techniques in separation and/or ionization of analytes complementary to commonly used procedures were described, which, so far, did not meet all requirements of sports drug testing. PMID- 20355155 TI - Subject-based profiling for the detection of testosterone administration in sport. PMID- 20355156 TI - Identification of the date-rape drug GHB and its precursor GBL by Raman spectroscopy. AB - Gamma hydroxybutyric acid (GHB), also known as 'liquid ecstasy', has recently become associated with drug-facilitated sexual assaults, known colloquially as 'date rape', due to the ability of the drug to cause loss of consciousness. The drug is commonly found 'spiked' into alcoholic beverages, as alcohol increases its sedative effects. Gamma hydroxybutyric acid and the corresponding lactone gamma-butyrolactone (GBL) will reach an equilibrium in solution which favours the lactone in basic conditions and GHB in acidic conditions (less than pH 4). Therefore, we have studied both GHB and GBL, as a mildly acidic beverage 'spiked' with GHB will contain both GHB and GBL. We report the analysis of GHB as a sodium salt and GBL, its precursor, using bench-top and portable Raman spectroscopy. It has been demonstrated that we are able to detect GHB and GBL in a variety of containers including colourless and amber glass vials, plastic vials and polythene bags. We have also demonstrated the ability to detect both GBL and GHB in a range of liquid matrices simulating 'spiked' beverages. PMID- 20355154 TI - Phytoestrogenic isoflavonoids in epidemiologic and clinical research. AB - Isoflavones (IFLs) are natural products to which humans have been traditionally exposed predominantly through soy foods; more recently humans are also exposed to them through soy protein addition to processed foods or through supplements. They are structurally similar to steroidal estrogens and can exert estrogenic or antiestrogenic effects depending on their concentrations and on the tissue considered. These properties qualify IFLs to be classified as phytoestrogens and are believed to account for many of the biological effects observed for soy and/or IFL exposure including benefits for bone and heart health or prevention of menopausal symptoms and certain types of cancer. In order to evaluate the function of IFLs, alone or when exposure happens through soy intake, pharmacokinetics and bioavailability are critical issues to be considered in epidemiologic and clinical research. For this purpose precise, accurate, robust, fast, and affordable techniques for IFL analyses are required. PMID- 20355157 TI - Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S 107 in doping control analysis. AB - Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca(2+) release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca(2+) leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4 benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S 107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI)-high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S 107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68 92%), lower limit of detection (0.1-0.2 ng/mL), intraday (5.2-18.5%) and interday (8.7-18.8%) precision as well as ion suppression/enhancement effects were determined. PMID- 20355158 TI - SDS-PAGE of recombinant and endogenous erythropoietins: benefits and limitations of the method for application in doping control. AB - Doping of athletes with recombinant and genetically modified erythropoietins (EPO) is currently detected by isoelectric focusing (IEF). The application of these drugs leads to a significant change in the isoform profile of endogenous urinary erythropoietin (uhEPO). Dynepo, MIRCERA, biosimilars with variable IEF profiles as well as active urines and effort urines have made additional testing strategies necessary. The new generation of small molecule EPO-receptor stimulating agents like Hematide will also challenge the analytical concept of detecting the abuse of erythropoiesis stimulating agents (ESA). By determining their apparent molecular masses with SDS-PAGE a clear differentiation between endogenous and exogenous substances also concerning new EPO modifications is possible. Due to the orthogonal character of IEF- and SDS-PAGE both methods complement each other. The additional benefits of SDS-PAGE especially in relation to active and effort urines as well as the detection of Dynepo were investigated. Due to significant differences between the apparent molecular masses of uhEPO/serum EPO (shEPO) and recombinant, genetically or chemically modified erythropoietins the presence of active or effort urines was easily revealed. The characteristic band shape and apparent molecular mass of Dynepo on SDS-PAGE additionally evidenced the presence of this substance in urine. A protocol for the detection of EPO-doping in serum and plasma by SDS-PAGE was developed. Blood appears to be the ideal matrix for detecting all forms ESA-doping in the future. PMID- 20355159 TI - Vibrational spectroscopic study of salbutamol hemisulphate. AB - Salbutamol hemisulphate is a relatively selective beta(2)-adrenergic agonist and is used as a bronchodilator. In this work, we present a detailed vibrational spectroscopic investigation of salbutamol hemisulphate using mid-infrared and near-infrared Fourier-transform (NIR-FT) Raman spectroscopies. These data are supported by quantum chemical calculations, which allow us to characterise the vibrational spectra of this compound reasonably. As such, this study could be viable for examining the way in which this drug interacts with its target molecules. PMID- 20355160 TI - Editorial. Recent advances in doping control initiated by anti-doping laboratories. PMID- 20355161 TI - The fight against doping: back on track with blood. PMID- 20355162 TI - Is anti-doping analysis so far from clinical, legal or forensic targets?: The added value of close relationships between related disciplines. AB - There are many areas of common interest between anti-doping laboratories and those working in the clinical, legal and forensic fields. In addition to methodological similarities, there are aspects of the findings in sport drug testing that overlap with other fields in such a way that sport drug testing and clinical, legal or forensic work may benefit from mutual interaction. Three recent examples are presented from the author's experience. Case report 1 concerns the clinical relevance of hCG findings in sport drug testing as potential indicators of the presence of a (testicular) tumour in athletes. Case report 2 refers to difficulties that accredited laboratories can encounter due to differences between national legal systems and the administrative regulation systems of sport authorities. The example involves a network of blood collection for further autologous transfusion. Case report 3 relates to additional forensic type investigations needed to interpret a situation where intoxication of a whole delegation was responsible for apparent doping cases. Clinical, legal and forensic fields must recognize the added value that some results and developments coming from anti-doping laboratories may have. At the same time anti-doping analysts should be aware of new issues, methodologies and problems appearing in related fields. PMID- 20355163 TI - Anti-doping testing at the 2008 European football championship. AB - Big sports events like the 2008 European Football Championship are a challenge for anti-doping activities, particularly when the sports event is hosted by two different countries and there are two laboratories accredited by the World Anti Doping Agency. This challenges the logistics of sample collection as well as the chemical analyses, which must be carried out timeously. The following paper discusses the handling of whereabouts information for each athlete and the therapeutic use exemption system, experiences in sample collection and transportation of blood and urine samples, and the results of the chemical analysis in two different accredited laboratories. An overview of the analytical results of blood profiling and growth hormone testing in comparison with the distribution of the normal population is also presented. PMID- 20355164 TI - SARCOSYL-PAGE: a new method for the detection of MIRCERA- and EPO-doping in blood. AB - The detection of doping with MIRCERA (the brand name for Continuous Erythropoietin Receptor Activator, or CERA) is hampered by the limited excretion of the rather large molecule (approximately 60 kDa) in urine. Blood (serum, plasma) in combination with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) appears to be the ideal matrix for detecting all forms of doping with erythropoiesis-stimulating agents (ESAs) because the apparent molecular masses of ESAs are different from the mass of human serum erythropoietin (shEPO). While SDS-PAGE has proven the most sensitive method for the detection of doping with Dynepo, the sensitivity of SDS-PAGE for MIRCERA is drastically decreased. By exchanging the SDS for SARCOSYL (SAR) in the sample and running buffers the sensitivity problem was solved. SARCOSYL, a methyl glycine based anionic surfactant, is only binding to the protein-part of MIRCERA but not to its polyethylene glycol (PEG)-chain, while SDS binds to both parts. In consequence, the monoclonal anti-EPO antibody (clone AE7A5) no longer interacts with the fully SDS-solubilized MIRCERA molecules. Only those molecules that contain SDS bound to the protein-chain are detected. Due to the inability of SARCOSYL to solubilize PEG-molecules, MIRCERA can be detected on SARCOSYL-PAGE with the same sensitivity as non-PEGylated epoetins. In a typical SAR-PAGE experiment, 200 microL of serum are used, which allows the direct detection of MIRCERA, recombinant epoetins (such as NeoRecormon, Dynepo, NESP), and shEPO in a single experiment and with high (i.e. femtogram) sensitivity. PMID- 20355165 TI - Temporal indication of cannabis use by means of THC glucuronide determination. AB - According to the regulations of the World Anti-Doping Agency (WADA), the use of cannabinoids is forbidden in competition. In doping controls, the detection of cannabinoid misuse is based on the analysis of the non-psychoactive metabolite 11 nor-9-carboxy-delta-9-tetrahydrocannabinol (carboxy-THC). The determination of values greater than 15 ng/mL in urine represents an adverse analytical finding; however, no accurate prediction of the time of application is possible as the half-life of carboxy-THC ranges between three and four days. Consequently the detection of carboxy-THC in doping control urine samples collected in competition might also result from cannabis use in out-of-competition periods. The analysis of the glucuronide of the pharmacologically active delta 9-tetrahydrocannabinol (THC-gluc) may represent a complementary indicator for the detection of cannabis misuse in competition.An assay for the determination of THC-gluc in human urine was established. The sample preparation consisted of liquid-liquid extraction of urine specimens, and extracts were analysed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Authentic doping-control urine samples as well as specimens obtained from a controlled smoking study were analysed and assay characteristics such as specificity, detection limit (0.1 ng/mL), precision (>90%), recovery ( approximately 80%), and extraction efficiency (90%) were determined. PMID- 20355166 TI - Screening for testosterone abuse in male athletes using the measurement of urinary LH, a revision of the paradigm. AB - The primary screening method for the detection of doping by athletes using synthetic versions of endogenous steroids such as testosterone relies on measurement of the ratio of testosterone (T) to epitestosterone (E) in urine. In 2005 the World Anti-Doping Agency (WADA) lowered the T/E value at which samples undergo further investigation from six to four. This has resulted in a large increase in the number of athletes with naturally elevated T/E ratios undergoing investigation without a corresponding increase in the number of proven doping offences involving testosterone.Our objective was to develop a new simple screening protocol that can, with high probability, not only distinguish athletes whose natural T/E values exceed four from those whose T/E values have been elevated by testosterone doping but also detect those athletes with naturally low T/E values that do not exceed four despite being administered testosterone.Testosterone (250 mg Sustanon) was administered weekly to a group of 47 young adult males for five weeks in a double-blind placebo controlled study and urine samples collected. The samples were analysed for steroid concentrations using GC/MS and for luteinizing hormone (LH) by immunoassay.The elevation of T/E that occurred in all subjects was accompanied by a significant reduction in urinary LH concentrations to levels that are rare in normal subjects.The appropriate measurement of urinary LH, with the measurement of T/E values, can markedly improve the efficiency of detection of doping with testosterone by male athletes, particularly those who have low natural T/E ratios. PMID- 20355167 TI - Analysis of non-ketoic steroids 17alpha-methylepithiostanol and desoxymethyl- testosterone in dietary supplements. AB - Dietary supplements containing 17alpha-methyl-2,3-epithio-5alpha-androstane 17beta-ol (17alpha-methylepithiostanol), which is a 17-methylated analogue of epithiostanol or a prodrug of desoxymethyltestosterone (17alpha-methyl-5alpha androst-2-en-17beta-ol), have recently appeared on the Internet. 17alpha Methylepithiostanol and desoxymethyltestosterone are classified as prohibited substances on the World Anti-Doping Agency (WADA) list. Two preparations, EPISTANE and P-PLEX, were obtained from the Internet so that their contents could be investigated. This study involved gas chromatography/mass spectrometry (GC/MS) analysis after trimethylsilyl (TMS) derivatization, liquid chromatography/mass spectrometry (LC/MS) in atmospheric pressure photoionization (APPI) mode and nuclear magnetic resonance (NMR) spectroscopy. Analysis using LC/MS in APPI mode would be a useful tool for detecting heat-labile and non-polar steroids.Although the labelling of EPISTANE indicates that it contains 17alpha-methyl-2alpha, 3alpha-epithio-5alpha-androstane-17beta-ol only, 17alpha-methyl-2beta,3beta epithio-5alpha-androstane-17beta-ol and desoxymethyltestosterone were identified in the supplement. The results showed that P-PLEX contained desoxymethyltestosterone and its isomer 17alpha-methyl-5alpha-androst-3-en-17beta ol. Urine samples can be screened after EPISTANE or P-PLEX administration using the normal screening procedure for anabolic steroids with GC/MS. PMID- 20355168 TI - Ethylglucuronide as a potential marker for alcohol-induced elevation of urinary testosterone/epitestosterone ratios. AB - The potential influence of alcohol consumption on endogenous steroids has already been described in the literature. In those studies the ethanol level after ingestion was monitored using its concentration in blood, urine or saliva. Corresponding methods are not commonly used in anti-doping laboratories. Ethylglucuronide (EtG), which can be easily detected by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), appears to be a more suitable parameter for this purpose. It is slowly excreted into the urine and indicates alcohol intake for a much longer period than blood or urinary alcohol and it is therefore routinely used for legal purposes as an alcohol consumption marker. In pharmacokinetic studies that aimed to establish calculation models after ethanol intake, the formation of EtG was observed to coincide with elevated urinary testosterone/epitestosterone (T/E) ratios. Similarly, large amounts of EtG were correlated with abnormal steroid profiles found in routine doping samples. In this pilot study, several cases with significantly elevated T/E ratios were associated with urinary EtG concentrations higher than 50 microg/mL. These findings confirmed recent intake of ethanol in considerable amounts and suggest a connection to changes in specific steroid profile parameters. Owing to the ease with which procedures to determine EtG can be carried out, and the potential for such procedures to be introduced into screening schemes, the inclusion of this marker in the final evaluation of suspicious outliers in T/E ratio longitudinal studies would seem to be very useful. PMID- 20355169 TI - Steroid metabolism in chimeric mice with humanized liver. AB - Anabolic androgenic steroids are considered to be doping agents and are prohibited in sports. Their metabolism needs to be elucidated to allow for urinary detection by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Steroid metabolism was assessed using uPA(+/+) SCID mice with humanized livers (chimeric mice). This study presents the results of 19-norandrost-4-ene-3,17-dione (19-norAD) administration to these in vivo mice. As in humans, 19-norandrosterone and 19 noretiocholanolone are the major detectable metabolites of 19-norAD in the urine of chimeric mice.A summary is given of the metabolic pathways found in chimeric mice after administration of three model steroid compounds (methandienone, androst-4-ene-3,17-dione and 19-norandrost-4-ene-3,17-dione). From these studies we can conclude that all major metabolic pathways for anabolic steroids in humans are present in the chimeric mouse. It is hoped that, in future, this promising chimeric mouse model might assist the discovery of new and possible longer detectable metabolites of (designer) steroids. PMID- 20355170 TI - Detection of mono-hydroxylated metabolites of stanozolol by HPLC-ESI (+) MS/MS in Indian sports persons. AB - The abuse of stanozolol is quite widespread in Indian sport. Its analysis is challenging and this has led to the development of new methods to improve its detection. A method was developed and validated for the detection of the three main monohydroxylated metabolites of stanozolol. The excretion profile of these metabolites was studied in four healthy male volunteers. The excretion study samples, after a single oral dose of drug, showed that 3'-OH-stanozolol was excreted at the highest concentration, followed by 16beta-OH stanozolol, with 4beta-OH stanozolol as the least excreted. Ninety-eight old doping samples with adverse analytical findings for 3'-OH-stanozolol were reanalysed using this method. This showed 3'-OH-stanozolol and 16beta-OH stanozolol in all the 98 samples whereas 4beta-OH-stanozolol was identified in 90 samples. The percentage of positive identifications of stanozolol in Indian sportspeople has increased markedly in the last five years, from 31.9% in 2004 to 81.8% in 2009; however, this may be due to the more effective detection of stanozolol metabolites. It can thus be concluded that the marked increase in percent positive of stanozolol in Indian sportspersons in 2009 may be due to the improved detection by a more effective LCMS/MS method. PMID- 20355171 TI - Application of FAIMS to anabolic androgenic steroids in sport drug testing. AB - Mass spectrometric identification of anabolic androgenic steroids challenges standard doping-control methods. To reveal a doping offence the presence of prohibited anabolic androgenic steroids at trace levels in the picogram-per millilitre range must be confirmed as reliable. Human urine samples containing epitrenbolone, metandienone metabolite (17beta -hydroxymethyl-17alpha-methyl-18 norandrost-1,4,13-trien-3-one), stanozolol, 16beta-hydroxystanozolol and 4beta hydroxystanozolol were analysed using LC-FAIMS-MS/MS. These substances are prohibited in sport according to World Anti-Doping Agency (WADA) regulations. Glucuronides were hydrolysed and prepared by liquid-liquid extraction. Excellent recovery and precision were obtained for all compounds. Linear calibration results for epitrenbolone and metandienone metabolite were obtained and concentration information could be determined in the ranges of reliable response between 750-1200 and 100-600 pg/mL, respectively. Limits of detection were estimated at 25 pg/mL (stanozolol), 50 pg/mL (metandienone metabolite, 16beta hydroxystanozolol), 100 pg/mL (4beta-hydroxystanozolol) and 500 pg/mL (epitrenbolone). The assay was applied to doping-control samples. For all analytes, LC-FAIMS-MS/MS resulted in excellent interference removal, which effectively extends the post-dose detection time. PMID- 20355172 TI - Combination of liquid-chromatography tandem mass spectrometry in different scan modes with human and chimeric mouse urine for the study of steroid metabolism. AB - Anabolic steroids are among the most frequently detected compounds in doping analysis. They are extensively metabolized and therefore an in-depth knowledge about steroid metabolism is needed. In this study, a liquid chromatography tandem mass spectometry (LC-MS/MS) method based on a precursor ion scan with a uPA-SCID mouse with humanized liver (a chimeric mouse) was explored for the detection of steroid metabolism. Methandienone was used as a model compound. The application of the precursor ion scan method in positive human samples and chimeric mice samples after methandienone administration allowed the detection of most steroid metabolites without any structural restriction. Three hitherto unreported metabolites were found using this approach. These metabolites were characterized using LC-MS/MS and feasible structures were proposed. The structure of one of them, 6-ene-epimethandienone, was confirmed by the synthesis of the reference compound. A selected reaction monitoring (SRM) method for the specific detection of all these metabolites has been developed. The application of this method to several human and chimeric mouse samples confirmed that more than 80% of the steroid metabolites were found in both samples. Only metabolites that are poorly detectable by LC-MS/MS were not detected in some urine samples. The metabolic nature of the unreported metabolites was also confirmed. A global strategy for the detection of steroid metabolites combining both human and chimeric mouse urine is proposed. PMID- 20355173 TI - Terbutaline sulfoconjugate: characterization and urinary excretion monitored by LC/ESI-MS/MS. AB - Terbutaline is a fast-acting beta(2)-adrenergic agonist used in the treatment of obstructive pulmonary diseases. Doping control for beta(2)-agonists, which are forbidden in sports by the World Anti-doping Agency (WADA), is performed in screening by liquid chromatography/mass spectrometry after hydrolysis of phase-II metabolites. In this study, the mono-sulfoconjugated phase-II metabolite of terbutaline was synthesized and the chemical structure was characterized by (1)H nuclear magnetic resonance spectrometry and high resolution/high accuracy Orbitrap mass spectrometry. The metabolite was designated as the phenolic esterified compound, which has been mentioned in most literature reports but has not been verified so far. The benzylic esterified compound was also synthesized and characterized by high-resolution/high accuracy Orbitrap mass spectrometry but was not detectable in urine samples from an excretion study performed after a single application of one terbutaline capsule (7.5 mg terbutaline sulfate salt). The phenolic sulfate of terbutaline was detected for two to four days after administration, whereas the unchanged terbutaline was detected for four to five days. A glucuronidated, disulfated or trisulfated phase-II metabolite of terbutaline was not found. The measurement of phase-II metabolites is planned to be incorporated into existing screening procedures to allow a faster sample preparation. PMID- 20355174 TI - Determination of 13C/12C ratios of urinary epitestosterone and its main metabolites 5alpha- and 5beta-androstane-3alpha, 17alpha-diol. AB - Epitestosterone (17alpha-hydroxy-androst-4-en-3-one, EpiT) belongs to the list of prohibited substances of the World Anti-Doping Agency (WADA). Although it possesses no anabolic effect, it is presumed to be misused by athletes in order to mask administration of testosterone (T) by lowering the urinary T/EpiT ratio.To improve detection, an excretion study with 40 mg of orally administered EpiT was conducted focusing on the metabolites of EpiT: 5alpha- and 5beta androstane-3alpha,17 alpha-diol (5aEpiD and 5bEpiD). A reference population of n = 74 volunteers was investigated to elucidate the urinary concentrations of these steroids.In order to prove whether an unusual finding in urinary concentrations or ratios is due to an illicit intake of steroids or due to physiological elevation, determination of carbon isotope ratios is advisable. A method for isotope ratio determination was developed to enable (13)C/(12)C ratios of EpiT, 5bEpiD, 5aEpiD, pregnanediol and androsterone and etiocholanolone to be measured from a single urine specimen. The method's validity was tested by applying linear mixing models and specificity was ensured by means of gas chromatography/mass spectrometry analysis. delta(13)C values at natural levels were determined with a reference population and both Delta values and corresponding reference limits were calculated.Considering the implemented EpiT-metabolites, a more than twofold extension of the detection time of EpiT administration was achieved with both the urinary concentration thresholds and the (13)C/(12)C ratios. PMID- 20355176 TI - A viable test for hGH? An interview with Prof. RIG Holt. Interviewed by Paul Trevorrow. PMID- 20355175 TI - Development of criteria for the detection of adrenosterone administration by gas chromatography-mass spectrometry and gas chromatography-combustion-isotope ratio mass spectrometry for doping control. AB - Adrenosterone (androst-4-ene-3,11,17-trione, 11-oxoandrostenedione) is an endogenous steroid hormone that has been promoted as a dietary supplement capable of reducing body fat and increasing muscle mass. It is proposed that adrenosterone may function as an inhibitor of the 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is primarily responsible for reactivation of cortisol from cortisone. The urinary metabolism of adrenosterone was investigated, after a single oral administration in two male subjects, by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion isotope ratio mass spectrometry (GC-C-IRMS). Substantially increased excretion of 11beta-hydroxyandrosterone, 11beta-hydroxyetiocholanolone, 11-oxoandrosterone and 11-oxoetiocholanolone was observed. Minor metabolites such as 3alpha,17beta dihydroxy-5beta-androstan-11-one, 3alpha-hydroxyandrost-4-ene-11,17-dione and 3alpha,11beta-dihydroxyandrost-4-en-17-one were also identified. The exogenous origin of the most abundant adrenosterone metabolites was confirmed by GC-C-IRMS according to World Anti-Doping Agency criteria. Through analysis of a reference population data set obtained from urine samples provided by elite athlete volunteers (n = 85), GC-MS doping control screening criteria are proposed: 11beta hydroxyandrosterone concentration greater than 10 000 ng/mL (specific gravity adjusted to 1.020) or 11beta-hydroxyandrosterone/11beta-hydroxyetiocholanolone ratio greater than 20.Urine samples fulfilling these screening criteria may be subjected to GC-C-IRMS analysis for confirmation of adrenosterone administration. PMID- 20355177 TI - Perinatal illicit drug use and fetal exposure: consequences and management with a public health approach. PMID- 20355178 TI - 13C/12C ratios of endogenous urinary steroids investigated for doping control purposes. AB - In order to detect the misuse of endogenous anabolic steroids such as testosterone by athletes a total of n = 1734 suspicious urine samples were investigated by gas chromatography/combustion/isotope ratio mass spectrometry throughout the years 2005, 2006 and 2007. The (13)C/(12)C ratio of a target substance (androsterone, a testosterone metabolite) was compared to the (13)C/(12)C ratio of an endogenous reference compound (11beta hydroxyandrosterone).N = 1340 samples were investigated due to elevated testosterone/epitestosterone ratios, with n = 87 (6.5%) exceptional findings regarding their isotopic ratios. An additional n = 164 samples were investigated because of elevated dehydroepiandrosterone concentrations, with n = 2 (1.2%) exceptional findings. The remainder were subjected to isotope ratio analysis because of elevated androsterone levels or because this was requested by sports federations.Significant differences between female and male samples were found for the (13)C/(12)C ratios of androsterone and 11beta-hydroxyandrosterone but not for samples taken in or out of competition.A further n = 645 samples originating from other World Anti-Doping Agency accredited laboratories, mainly throughout Europe as well as South America, South Africa and Southeast Asia, were investigated. The (13)C/(12)C ratios of the urinary steroids differ significantly for each geographical region, reflecting the dietary status of the individuals.The system stability over time has been tested by repeated injections of a standard solution and repeated processing of frozen stored blank urine. Despite a drift over time in absolute (13)C/(12)C ratios, no significant change in the difference of (13)C/(12)C (11beta-hydroxyandrosterone) minus (13)C/(12)C (androsterone) could be observed. PMID- 20355179 TI - Computational and vibrational spectroscopic studies of ipratropium bromide. AB - In this study, ipratropium bromide is investigated using vibrational spectroscopy and quantum chemical calculations. The structure of ipratropium bromide was optimised using density functional theory calculations and the geometry optimisation has been carried out on two conformations with and without intramolecular hydrogen bonding. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra could be matched with the experimental spectra and a description of the modes is given. By analysis of the theoretical vibrational modes, it is shown that ipratropium bromide specimens are likely to be a mixture of the two conformations with and without intramolecular hydrogen bonding. In addition, several spectral features and band intensities in the CH and OH stretching regions are explained. Quantum mechanical calculations allowed improved understanding of ipratropium bromide and its vibrational spectra. PMID- 20355180 TI - Proteolysis and autolysis of proteases and the detection of degradation products in doping control. AB - The determination of protein- or peptide-based performance-enhancing pharmaceuticals has gained increasing attention in sports drug testing in recent decades. Proteases possess a high potential for use in the manipulation of regular urine specimens, interfering with established doping control procedures for proteins or peptides. Hence, the present approach was developed to identify degradation products directly from proteases with exogenous origin in urine samples by means of SDS-PAGE and capillary liquid chromatography-Orbitrap (tandem) mass spectrometry. The mass spectrometric identification was accomplished by database search considering the accurate monoisotopic precursor mass with data dependent MS/MS analysis and no setting for specific cleavage site(s) or enzyme(s). The main characteristics of the method were shown in an exemplary way for the proteases Papain, Bacillolysin, Trypsin and Subtilisin with sufficient results for specificity, limit of detection, working range, precision and recovery after incubation. All experiments were performed with fortified urine samples under consideration of assumed realistic conditions for adulteration by cheating sportsmen. PMID- 20355181 TI - Capillary electrophoresis with electrochemiluminescence detection for simultaneous determination of proline and fleroxacin in human urine. AB - The content of free proline (Pro) in body fluids is a biological parameter for patients with renal insufficiency and chronic uraemia. Fleroxacin (FLX) must be used cautiously because of adverse reactions. Its dosage must be adjusted according to the degree of renal insufficiency. In a clinical setting the simultaneous determination of Pro and FLX in body fluids is necessary for the rational utilization of FLX. A capillary electrophoresis (CE) method based on electrochemiluminescence (ECL) detection with Ru(bpy)(3) (2+) was developed for the simultaneous determination of Pro and FLX in human urine. Parameters related to separation and detection were investigated and optimized. The most favourable resolution and high sensitivity were obtained using a 15 mM phosphate buffer at pH 9.6 with the detection potential at 1.15 V. Under optimized conditions, the standard curves were linear in the range of 0.1-80 microg/mL for Pro and 0.1-100 microg/mL for FLX. Detection limits(3sigma) of 0.3 ng/mL for FLX and 0.02 microg/mL for Pro were obtained. Relative standard derivations (RSDs) of the ECL intensity and the migration time were 3.2% and 0.9% for 4 microg/mL Pro and 3.7% and 1.2% for 4 microg/mL FLX, respectively. The recoveries were in the range of 94.8-99.6% for Pro with RSDs of 2.8%-3.6% and 94.7-97.8% for FLX with RSDs of 2.9%-3.7%. The proposed method was successfully applied to determine the amounts of Pro and FLX in human urine. PMID- 20355182 TI - LC-MS: a powerful tool in workplace drug testing. AB - Workplace drug testing is a well-established application of forensic toxicology and it aims to reduce workplace accidents caused by affected workers. Several classes of abused substances may be involved, such as alcohol, amphetamines, cannabis, cocaine, opiates and also prescription drugs, such as benzodiazepines. The use of alternative biological specimens such as hair, oral fluid or sweat in workplace drug testing presents several advantages over urinalysis-mainly the fact that sample collection can be performed easily without infringing on the examinee's privacy, so the subject is more likely to perform the test. However, drugs are usually present in these alternative specimens at low concentrations and the amount of sample available for analysis is small. The use of highly sensitive techniques is therefore necessary. In fact, the successful interface of liquid chromatography with mass spectrometry (LC-MS) has brought a new light into bioanalytical and forensic sciences as it allows the detection of drugs and metabolites at concentrations that are difficult to analyse using the more commonly adopted GC-MS based techniques. This paper will discuss the importance of LC-MS in supporting workplace drug-testing programmes. The combination of LC MS with innovative instrumentation such as triple quadrupoles, ion traps and time of-flight mass spectrometers will also be focused. PMID- 20355183 TI - Testing employees. PMID- 20355184 TI - Enantioseparation of cetirizine by chromatographic methods and discrimination by 1H-NMR. AB - Cetirizine is an antihistaminic drug used to prevent and treat allergic conditions. It is currently marketed as a racemate. The H1-antagonist activity of cetirizine is primarily due to (R)-levocetirizine. This has led to the introduction of (R)-levocetirizine into clinical practice, and the chiral switching is expected to be more selective and safer. The present work represents three methods for the analysis and chiral discrimination of cetirizine. The first method was based on the enantioseparation of cetirizine on silica gel TLC plates using different chiral selectors as mobile phase additives. The mobile phase enabling successful resolution was acetonitrile-water 17: 3, (v/v) containing 1 mM of chiral selector, namely hydroxypropyl-beta-cyclodextrin, chondroitin sulphate or vancomycin hydrochloride. The second method was a validated high performance liquid chromatography (HPLC), based on stereoselective separation of cetirizine and quantitative determination of its eutomer (R)-levocetirizine on a monolithic C18 column using hydroxypropyl-beta-cyclodextrin as a chiral mobile phase additive. The resolved peaks of (R)-levocetirizine and (S)-dextrocetirizine were confirmed by further mass spectrometry. The third method used a (1)H-NMR technique to characterize cetirizine and (R)-levocetirizine. These methods are selective and accurate, and can be easily applied for chiral discrimination and determination of cetirizine in drug substance and drug product in quality control laboratory. Moreover, chiral purity testing of (R)-levocetirizine can also be monitored by the chromatographic methods. PMID- 20355185 TI - Synthesis of labeled BCX-4208, a potent inhibitor of purine nucleoside phosphorylase. AB - BCX-4208, a novel inhibitor of the enzyme purine nucleoside phosphorylase, mimics the charged ribosyl oxocarbenium ion formed during the transition state of the enzyme-catalyzed C-N bond cleavage of nucleosides. A slow-onset, tight-binding inhibitor with a Ki(*) of 16 +/- 1.4 pM, BCX-4208 is one of the most potent inhibitors known for the enzyme. In support of our BCX-4208 clinical program, a mass spectrometric assay has been developed that required labeled BCX-4208 as an internal standard. The synthesis of [(2)H](2)-BCX-4208 and [(13)C]-BCX-4208 is described in this report. PMID- 20355186 TI - Dysprosium-sensitized chemiluminescence system for the determination of enoxacin in pharmaceutical preparations and biological fluids with flow-injection sampling. AB - A novel trivalence dysprosium(Dy(3+))-sensitized chemiluminescence method was developed for the first time for the determination of enoxacin (ENX) using flow injection sampling based on the chemiluminescence (CL) associated with the reaction of the Dy(3+)-cerium(Ce(IV))-S(2)O(3) (2-)-ENX system and the Dy(3+) MnO(4) (-) S(2)O(3) (2-)-ENX system. The analytical conditions for CL emission were investigated and optimized. The relationship between the CL intensity of ENX and its concentration has good linearity, with a correlation coefficient of 0.9984-0.9994. The limit of detection (LOD, 3sigma) was 0.20 ng/mL for the Dy(3+) ENX-S(2)O(3)(2-)-Ce(IV)-H(2)SO(4) system and 0.22 ng/mL for the Dy(3+)-ENX S(2)O(3)(2-)-MnO(4) (-)-HNO(3) system. The relative standard deviation (RSD, n = 11) was 1.8% for 11 determinations of 60 ng/mL ENX. The proposed method was applied to the analysis of ENX in injections, serum and urine samples with a recovery of 98%-105%. A possible mechanism for this sensitized CL reaction is discussed by comparing the CL spectra with the fluorescence emission spectra. The proposed method represents a wide linear range, high sensitivity and accuracy, and can be used for the routine determination of ENX in pharmaceutical preparations and biological fluids. PMID- 20355187 TI - Counterfeiting in performance- and image-enhancing drugs. AB - The current drastic escalation in obesity may be contributing to the exponential rise in drugs used for image enhancement. Drugs such as anabolic-androgenic steroids (AAS) are perceived as a viable method of achieving a perfect physique. They are also the most widely abused drugs in sport. The Internet has encouraged the abuse of expensive drugs, particularly human growth hormone (hGH), resulting in increased importation for personal use. The substantial increase in this market has opened up avenues for counterfeiting, estimated as a multi-million pound business. The acute adverse effects from contaminated vials may result in a variety of pathologies including communicable diseases. In 2007, in the UK, a series of intramuscular abscesses, requiring surgical treatment, led us to study samples obtained from the underground market. The analysis of 38 parenteral samples and 19 oral samples of tablets was performed by a World Anti-Doping Agency (WADA) accredited laboratory, in an attempt to establish the extent of available counterfeit products. Fifty-three per cent (20) of the injectable AAS esters and 21% (4) of the oral tablets were counterfeit. Culture and sensitivity revealed the presence of skin commensal organisms, which may have contributed to the development of the abscesses. Users of AAS and hGH for sport, including bodybuilding, are currently risking their health because of counterfeit and poorly controlled products. PMID- 20355188 TI - Detection of the protease bacillolysin in doping-control urine samples. PMID- 20355189 TI - Preservatives in liquid pharmaceutical preparations. PMID- 20355190 TI - Special issue-murders by drugs. PMID- 20355191 TI - Murders by drugs-past and present. PMID- 20355192 TI - Back to the roots of modern analytical toxicology: Jean Servais Stas and the Bocarme murder case. AB - In 1850 the Belgian Count Hypolyte Visart de Bocarme was accused of having killed his brother-in-law Gustave Fougnies by poisoning with nicotine. Bocarme had isolated nicotine from tobacco leaves (Nicotiana tabacum). J. S. Stas (1813-1891) was committed expert and managed to convince the poisoner. He was the first scientist to deproteinize organ tissues by alcohol and could successfully identify nicotine after diethyl ether extraction from the victim's organs. During court trial this identification was challenged by his mentor M. J. B. Orfila from Paris, who had stated 3 years before, that it would never be possible to isolate and identify organic poisons from organ tissues. PMID- 20355193 TI - Multi target analysis of putrefactive specimens by liquid chromatography-tandem mass spectrometry to prove multiple poisonings by hypnotics and muscle relaxants. AB - The muscle relaxant rocuronium and the hypnotics etomidate, diazepam and midazolam were candidate poisons in a case of a suspected series of fatal intoxications in a hospital. A robust, specific and sensitive multi-target screening procedure was established to identify unequivocally the parent compounds and diagnostic metabolites and artefacts in putrefied specimens, obtained from exhumed bodies. The analytical findings of relevant compounds could be traced partially back to authorised therapeutic measures, whereas the identification of rocuronium proved potentially lethal intoxications in 13 (of a total number of 42) cases. Moreover, the detection of certain hypnotics revealed an improper administration of these compounds in another nine cases, which suggested manipulation but was not indicative of fatal intoxications. Quantitative estimations of substance concentrations were highly correlated with the post-mortem time intervals and did not reveal any information on doses, initial serum concentrations or toxicological effects. PMID- 20355194 TI - Murder by insulin: suspected, purported and proven-a review. AB - Murder by insulin-whether attempted, suspected or proven-is rare. Only 66 cases worldwide could be found for this review. A conviction was secured in 31 cases and additional weapon was employed in 11. Differentiation of attempted homicide from Munchausen syndrome by proxy in the young and from 'mercy killing' in the elderly was not attempted. Most perpetrators were close relatives and most victims were alive when discovered and responded to treatment. Hypoglycaemia is the first clue to homicidal insulin use in living subjects and requires the demonstration of a plasma insulin concentration of generally more than 1000 pmol/L and undetectable plasma C-peptide concentration to establish the diagnosis. Serum glucose measurements are valueless in victims found dead. The presence near the body of insulin vials, syringes or needles, loose talk by the suspected perpetrator or their ready access to insulin may be the only clue. The demonstration of insulin in tissue around an injection site by immunohistopathology or by measuring it in an extract clinches the diagnosis. Immunoassays suitable for clinical use to detect and measure insulin and C peptide are subject to random errors and cannot be relied upon unless special precautions including separation by gel filtration or HPLC are undertaken prior to analysis. They do not detect or measure accurately a new generation of synthetic insulin analogues. Mass spectrometry will be required to do this and to validate clinical immunoassays, upon which convictions have always had to rely in the past. PMID- 20355195 TI - Murder by poisoning: successful analytical investigations of spectacular cases in Austria. AB - To prove murder by poisoning requires the application of analytical toxicology to detect the fatal substance and clear up the cause of death. Improvements in the development of mass spectrometry in combination with high-resolution chromatographic methods are steadily enhancing detection and identification power but making use of these advances relies on proper sample preparation as well as on knowledge about the chemical nature of the substances and their bio transformation products. This review gives examples of case reports with successful analytical investigations of murder by poisoning in spectacular Austrian cases involving low molecular weight. PMID- 20355196 TI - Ricin poisoning and forensic toxicology. AB - Ricin is one of the most fascinating poisons due to its high toxicity: as little as 500 microg can kill an adult. It gained fame by its use in the so-called 'umbrella murder' to kill the Bulgarian dissident Georgi Markov in 1978. Ricin also became known as a potential bio-terror agent to which people could be exposed through the air, food, or water. The origin, biochemistry, toxicity, and analytical procedures for the determination of ricin are summarized. The homicide of Markov is described as well as recent cases of criminal ricin use. PMID- 20355197 TI - Interpretation of urinary concentrations of pseudoephedrine and its metabolite cathine in relation to doping control. AB - Until the end of 2003 a urinary concentration of pseudoephedrine exceeding 25 microg/mL was regarded as a doping violation by the World Anti-Doping Agency. Since its removal from the prohibited list in 2004 the number of urine samples in which pseudoephedrine was detected in our laboratory increased substantially. Analysis of 116 in-competition samples containing pseudoephedrine in 2007 and 2008, revealed that 66% of these samples had a concentration of pseudoephedrine above 25 microg/mL. This corresponded to 1.4% of all tested in competition samples in that period. In the period 2001-2003 only 0.18% of all analysed in competition samples contained more than 25 microg/mL. Statistical comparison of the two periods showed that after the removal of pseudoephedrine from the list its use increased significantly. Of the individual sports compared between the two periods, only cycling is shown to yield a significant increase.Analysis of excretion urine samples after administration of a therapeutic daily dose (240 mg pseudoephedrine) in one administration showed that the threshold of 25 microg/mL can be exceeded. The same samples were also analysed for cathine, which has currently a threshold of 5 microg/mL on the prohibited list. The maximum urinary concentration of cathine also exceeded the threshold for some volunteers. Comparison of the measured cathine and pseudoephedrine concentrations only indicated a poor correlation between them. Hence, cathine is not a good indicator to control pseudopehedrine intake. To control the (ab)use of ephedrines in sports it is recommended that WADA reintroduce a threshold for pseudoephedrine. PMID- 20355198 TI - A reversed-phase high-performance liquid chromatography method for bovine serum albumin assay in pharmaceutical dosage forms and protein/antigen delivery systems. AB - Bovine serum albumin (BSA) is among the most widely used proteins in protein formulations as well as in the development of novel delivery systems as a typical model for therapeutic/diagnostic proteins and the new versions of vaccines. The development of reliable and easily available assay methods for quantitation of this protein would therefore play a crucial role in these types of studies. A simple gradient reversed-phase high-performance liquid chromatography with ultra violet detection (HPLC-UV) method has been developed for quantitation of BSA in dosage forms and protein delivery systems. The method produced linear responses throughout the wide BSA concentration range of 1 to 100 micro g/mL. The average within-run and between-run variations of the method within the linear concentration range of BSA were 2.46% and 2.20%, respectively, with accuracies of 104.49% and 104.58% for within-run and between-run samples, respectively. The limits of detection (LOD) and quantitation (LOQ) of the method were 0.5 and 1 microg/mL, respectively. The method showed acceptable system suitability indices, which enabled us to use it successfully during our particulate vaccine delivery research project. PMID- 20355199 TI - Sensitive and fast identification of urinary human, synthetic and animal insulin by means of nano-UPLC coupled with high-resolution/high-accuracy mass spectrometry. AB - The double-chain polypeptide insulin and its synthetic (Insulin Glulisine, Insulin Aspart, Insulin Glargine, or Insulin Lispro) or animal analogues (porcine insulin or bovine insulin) are potential performance-enhancing agents in elite sports or potentially effective toxins in forensic science.The present study demonstrates an analytical method to purify the insulins simultaneously from urine specimens with an approach based on immunoaffinity isolation, using coated magnetic beads (anti-mouse) and a primary anti-insulin antibody (IgG, monoclonal). The extracts were purified sufficiently for separation by means of nano-flow liquid chromatography coupled with nano-scale high-resolution, high accuracy ESI-MS/MS. Elucidation of collision-induced dissociations with product ion experiments using the fivefold protonated precursor ion of each target analyte enabled all synthetic and animal insulins to be differentiated from their human counterpart, which was particularly important for Lispro, possessing the same molecular mass as human insulin.The method was fully validated for specificity, limit of detection (LOD, 0.5 fmol/mL), precision (<20%), recovery (approximately 30%) and linearity (2-40 fmol/mL) for all target analytes. PMID- 20355200 TI - Stability-indicating chemometric methods for the determination of pyritinol dihydrochloride. AB - Three multivariate calibration methods, including classical least square with nonzero intercept (CLS), principal component regression (PCR) and partial least square (PLS), have been used for the determination of pyritinol dihydrochloride in the presence of its degradation product. The CLS, PCR and PLS techniques are useful in spectral analysis because the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry has greatly improved the precision and predictive abilities of these multivariate calibrations. A training set was constructed for the mixture and the best model was used for the prediction of the concentration of the selected drug. The proposed procedures were applied successfully in the determination of pyritinol dihydrochloride in laboratory-prepared mixtures and in commercial preparations. Pyritinol dihydrochloride was analysed with mean accuracies 99.99 +/- 0.905, 99.91 +/- 0.966 and 99.92 +/- 0.962 using the CLS, PCR and PLS methods respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed procedures were found to be rapid and simple and required no preliminary separation. They can therefore be used for the routine analysis of pyritinol dihydrochloride in quality-control laboratories. PMID- 20355201 TI - Quantitation of tetrahydrocannabinol in hair using immunoassay and liquid chromatography with tandem mass spectrometric detection. AB - A quantitative analytical procedure for the determination of Delta(9) tetrahydrocannabinol (THC) in hair has been developed and validated using liquid chromatography with tandem mass spectral detection (LC-MS/MS). Specimens that were determined as containing cannabinoids following immunoassay testing were quantified using solid-phase extraction followed by liquid chromatographic separation and tandem mass spectral detection in positive electrospray ionization mode. For confirmation, two transitions were monitored and one ratio determined. Samples being reported as positive were required to have both transitions present, the ratio of quantifying transition to qualifying transition being within 20% of that determined from known calibration standards. The limit of quantitation and the limit of detection was 10 pg/mg. The percentage recovery of the THC from hair at 20 pg/mg was 56% and a matrix effect of the hair showed an ion suppression percentage of -51%. The immunochemical screening method was performed following a rapid aqueous extraction, requiring only 10 mg of hair; the confirmatory procedure required 20 mg of hair. The methods were applied to proficiency specimens from the Society of Hair Testing, which had been received in August 2008. PMID- 20355202 TI - Thermal stability studies of 5-fluorouracil using diffuse reflectance infrared spectroscopy. AB - 5-Fluorouracil is one of the oldest chemotherapy drugs and it has been in use for decades. It is an active medicine against several types of cancer and effectively blocks the replication of DNA viruses. The present study assessed the potential of diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy to determine the thermal stability of 5-fluorouracil. Infrared spectra of the drug before and after exposure to thermal radiation at different temperatures were collected in diffuse reflectance mode using a Fourier transform infrared (FTIR) spectrophotometer. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were carried out simultaneously to confirm and support the results of infrared spectroscopy. The DRIFT spectra reveal that the drug shows good thermal stability up to 275 degrees C and undergoes complete thermal breakdown at about 285 degrees C. The results of DSC and XRD analysis also give the same information, which support the implementation of diffuse reflectance infrared spectroscopy for the determination of thermal stability of 5-fluorouracil. PMID- 20355203 TI - Erythropoiesis-stimulating agents: development, detection and dangers. AB - Epoetin alfa, the first member of the family of erythropoiesis stimulating agents (ESAs), was introduced to the market in 1989. Since then development has progressed to epoetins of the third generation. Currently drugs that use alternative approaches to stimulate erythropoiesis are under development. Uptake of all available ESAs into doping has occurred rapidly after their introduction. A multitude of dangers to health are associated with the illicit use of these substances. Different approaches to detect ESAs in doping control have been developed to comply with the very diverse nature of the compounds used. Future developments in the field of ESA require the development of new techniques in doping analysis. This review gives an overview of the development of ESA and its detection methods as well as future developments. [Correction made here after initial online publication] PMID- 20355204 TI - Generic sample preparation and dual polarity liquid chromatography-time-of-flight mass spectrometry for high-throughput screening in doping analysis. AB - The requirements on initial testing in doping control are getting tighter regarding efficiency and speed while the scope of analytes is getting more diverse and, consequently, the need for high-throughput methods is apparent. In this study, a comprehensive screening method for doping agents in human urine is presented, based on solid phase extraction (SPE) and liquid chromatography-time of-flight mass spectrometry (LCTOFMS). The method covers most of the compound groups in the list of prohibited substances by World Anti-Doping Agency (WADA). Mixed-mode SPE on two types of sorbent and the use of negative ionization mode besides the commonly used positive mode in electrospray ionization (ESI) allowed detection of acidic compounds, such as sulpho-conjugated metabolites. A run time of 8 minutes for each of the two ESI polarities was achieved. The method was validated regarding relative ionization efficiency, selectivity and signal to noise at the WADA's minimum required performance limit (MRPL) level, resulting in the acceptance of 197 compounds. A selection of 20 compounds was submitted for a more thorough validation, including extraction recovery, repeatability and linearity. Recovery and linearity (R(2)) varied mainly between 83-115% and 0.78 0.99, respectively. Median values for repeatability at the MRPL and 10 x MRPL levels were below 20%. A mean and median mass accuracy of 1.2 and 0.80 mDa, respectively, was achieved. The present method represents at the moment the widest coverage of low molecular weight prohibited substances for the screening in sports, providing an approach for further rationalisation of the analytical work-flow in the doping control laboratories. PMID- 20355205 TI - Spectroscopic study of the reaction mechanism of buspirone interaction with iodine and tetracyanoethylene reagents and its applications. AB - The reactions between the drug buspirone (busp) in its base form and iodine amphoteric reagent (n-donor and/or sigma-acceptor) and with tetracyanoethylene as a pi-acceptor reagent (TCNE) have been studied spectrophotometrically at different reactant concentrations, time intervals, temperatures, and with different solvents and wavelengths, with the aim of selecting the conditions that give the most suitable molar extinction coefficients. This study aims chiefly to throw light on the nature of these reactions and to select the most proper conditions for spectrophotometric application of these reagents to determine this biologically active drug used in treating different diseases. The reaction mechanism involves the formation of busp-I(2) outer and inner sphere complexes. The separated busp-I(2) solid product obtained was investigated using elemental analyses, FT-IR, thermal analyses (TA) and electron ionization mass spectrometry (EI-MS) and was found to be biologically active. The reaction mechanism of busp TCNE involves the formation of a charge transfer (CT) complex. The analytical parameters of the proposed spectrophotometric procedures were calculated. These procedures were applied in the analysis of busp in its formulations as a drug used to treat psychiatric illnesses. The values of the Sandell sensitivity, standard deviation (SD), relative standard deviation (RSD) and recovery percentage show the high sensitivity of these procedures. This study also presents a promising new busp-I(2) drug derivative that can be used more efficiently for the same purposes as its parent. It gives a clear idea about the possible metabolites and metabolic pathways of busp and its derivative that may occur in vivo. PMID- 20355206 TI - Development and validation of an infrared spectroscopy-based method for the analysis of moisture content in 5-fluorouracil. AB - The determination of moisture content in pharmaceuticals is very important as moisture is mainly responsible for the degradation of drugs. Degraded drugs have reduced efficacy and could be hazardous. The objective of the present work is to replace the Karl Fischer (KF) titration method used for moisture analysis with a method that is rapid, involves no toxic materials and is more effective. Diffuse reflectance infrared (IR) spectroscopy, which is explored as a potential alternative to various approaches, is investigated for moisture analysis in 5 fluorouracil, an anticancer drug. A total of 150 samples with varying moisture content were prepared in laboratory by exposing the drug at different relative humidities, for different time intervals. Infrared spectra of these samples were collected with a Fourier transform infrared (FTIR) spectrophotometer using a diffuse reflectance accessory. Reference moisture values were obtained using the Karl Fischer titration method. A number of calibration models were developed using the partial least squares (PLS) regression method. A good correlation was obtained between predicted IR values and reference values in the calibration and validation set. The derived calibration curve was used to predict moisture content in unknown samples. The results show that IR spectroscopy can be used successfully for the determination of moisture content in the pharmaceutical industry. PMID- 20355207 TI - Stability-indicating methods for the determination of a mixture of almitrine and raubasine by derivative spectrophotometry. AB - A second-derivative spectrophotometric method ((2)D) and a derivative ratio spectrum zero crossing ((1)DD) method were used to determine raubasine and almitrine dismesylate in the presence of raubasine degradation product, using methanol as a solvent. Linear relationships were obtained in the range from 6-20 microg ml(-1) raubasine for the ((2)D) method and 12-24 microg ml(-1) almitrine dismesylate for the ((1)DD) method. By applying these methods it was possible to determine raubasine in its pure powdered form with an accuracy of 99.93 +/- 1.116 (n = 8) for the ((2)D) method and almitrine dismesylate with an accuracy of 99.98 +/- 0.602 (n = 7) for the ((1)DD) method.Laboratory-prepared mixtures containing different ratios of raubasine, almitrine dismesylate and raubasine degradation product were analysed and the proposed methods were valid up to 50% of raubasine degradation product. They were found to be suitable stability-indicating assay methods for raubasine and almitrine dismesylate in pharmaceutical formulations. PMID- 20355208 TI - Prevalence of antidepressants and biosimilars in elite sport. AB - The use of prescribed antidepressants by athletes has not been restricted in human sports since 2003, after the antidepressants bupropion and amineptine were removed from the list of prohibited substances. Recent awareness of antidepressants has been stimulated by reports from the media concerning possible misuse of antidepressants among healthy athletes. The prevalence of antidepressants has been monitored over the past ten years with screening procedures routinely used by WADA-accredited laboratories. The growth in antidepressant use among athletes peaked in 2007 and 2008 after a modest increase over the first eight years of this survey. Pharmacy prescriptions for antidepressants in Germany did not show a correlated growth during this period. The increasing variety of antidepressant medications has led to a continued increase in the diversity of antidepressant substances used by athletes and the 'normal' population. The number of different sports affected by the presence of antidepressants has increased in the past decade, especially in endurance sports. The predominance of female antidepressant users in the normal population was reflected in the athletes' group. We concluded from our results that the development of antidepressant prevalence in elite sports did not correlate with that among the general public in Germany. PMID- 20355209 TI - The hunt for gene dopers. AB - Gene doping, the abuse of gene therapy for illicit athletic enhancement, is perceived as a coming threat and is a prime concern to the anti-doping community. This doping technique represents a significant ethical challenge and there are concerns regarding its safety for athletes. This article presents the basics of gene doping, potential strategies for its detection and the role of promising new technologies in aiding detection efforts. These include the use of lab-on-a-chip techniques as well as nanoparticles to enhance the performance of current analytical methods and to develop new doping detection strategies. PMID- 20355210 TI - Elephant in the room? The methodological implications for public health research of performance-enhancing drugs derived from the illicit market. AB - 'All scientific work is incomplete-whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.' PMID- 20355211 TI - Validated stability-indicating TLC method for the determination of noscapine. AB - A sensitive, selective, precise and stability-indicating thin-layer chromatographic (TLC) method was developed and validated for the analysis of noscapine, both as a bulk drug and in its formulation. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform-methanol (10:0.5 v/v). Densitometric analysis of noscapine and its degradation products was carried out in the absorbance mode at 254 nm. This system was found to give compact symmetrical spots for noscapine (R(f) value 0.85 +/- 0.04). Noscapine was subjected to acid and alkali hydrolysis, oxidation and photo degradation. The drug undergoes photo degradation and also degrades under acidic and basic conditions. The prepared degradation products were identified and verified through infrared (IR) and mass spectral analyses. The degraded products were also well resolved from the pure drug with significantly different R(f) values and they were quantitatively determined. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the 1.0-10.0 microg, 0.4-3.2 microg, 1.0-9.0 microg and 0.5-5.0 microg/band ranges for noscapine, cotarnine, meconine and opionic acid, respectively. The polynomial regression analysis for the calibration plots showed a good polynomial relationship with r(2) of 0.9998, 9989, 9996 and 0.9997 for noscapine and its three degradation products, cotarnine, meconine and opionic acid, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of noscapine. As this approach could effectively separate the drug from its degradation products it can be employed as a stability indicating method in Quality Control laboratories. PMID- 20355212 TI - Simultaneous determination of metformin hydrochloride and pioglitazone hydrochloride in binary mixture and in their ternary mixture with pioglitazone acid degradate using spectrophotometric and chemometric methods. AB - In this work two well known oral hypoglycemic drugs that are administered in combination for patients with type-II diabetes were simultaneously determined. Several spectrophotometric methods were developed and validated for the determination of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO) and pioglitazone acid degradate (PIO Deg). Derivative, ratio derivative, isosbestic and chemometric-assisted spectrophotometric methods were developed. The first derivative (D(1)) method was used for the determination of MET in the range of 5-30 microg x mL(-1) and PIO in the range of 10-90 microg x mL(-1) by measuring the peak amplitude at 247 nm and 280 nm, respectively. The concentration of PIO was calculated directly at 268 nm. The first derivative of ratio spectra (DD(1)) method used the peak amplitudes at 238 nm and 248.6 nm for the determination of MET in the range of 5-30 microg x mL(-1). In the isosbestic point method (ISO), the total mixture concentration was calculated by measuring the absorbance at 254.6 nm. Classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-2) were used for the quantitative determination of MET, PIO and PIO Deg. The methods developed have the advantage of simultaneous determination of the cited components without any pre-treatment. Resolution and quantitative determination of PIO degradate with a minimum concentration of 3 microg x mL(-1) in drug samples was done. The proposed methods were successfully used to determine each drug and the acid degradate in a laboratory-prepared mixture and pharmaceutical preparations. The results were statistically compared using one-way analysis of variance (ANOVA). The methods developed were satisfactorily applied to the analysis of the two drugs in pharmaceutical formulations. PMID- 20355213 TI - Voltammetric determination of sulfamethoxazole at a multiwalled carbon nanotube modified glassy carbon sensor and its application studies. AB - Sulfamethoxazole (SMX) is an anti-bacterial sulfonamide. It prevents the formation of dihydrofolic acid, a compound that bacteria need in order to survive. The present work details the voltammetric analysis of SMX at a multiwalled carbon nanotube (MWCNT)-Nafion modified glassy carbon electrode (GCE). Sulfamethoxazole gives a well defined oxidation peak at 0.74 V in 0.1 M phosphate buffer solution (PBS) of pH 8.0. The experimental parameters such as the amount of MWCNT-Nafion suspension, the pH of the supporting electrolyte and scan rate were optimized and a direct electrochemical method for the determination of SMX was developed. Under optimum conditions the oxidation peak current is linear to the concentration of SMX in the range 1 x 10(-2) - 5 x 10( 5) M with a detection limit of 1 x 10(-5) M. The MWCNT/GCE showed good stability, selectivity and was successfully used to quantify SMX in pharmaceutical formulations and urine sample. PMID- 20355214 TI - Enhancement in sample collection for the detection of MDMA using a novel planar SPME (PSPME) device coupled to ion mobility spectrometry (IMS). AB - Trace detection of illicit drugs challenges the scientific community to develop improved sensitivity and selectivity in sampling and detection techniques. Ion mobility spectrometry (IMS) is one of the prominent trace detectors for illicit drugs and explosives, mostly due to its portability, high sensitivity and fast analysis. Current sampling methods for IMS rely on wiping suspected surfaces or withdrawing air through filters to collect particulates. These methods depend greatly on the particulates being bound onto surfaces or having sufficient vapour pressure to be airborne. Many of these compounds are not readily available in the headspace due to their low vapour pressure. This research presents a novel SPME device for enhanced air sampling and shows the use of optimized IMS by genetic algorithms to target volatile markers and/or odour signatures of illicit substances. The sampling method was based on unique static samplers, planar substrates coated with sol-gel polydimethyl siloxane (PDMS) nanoparticles, also known as planar solid-phase microextraction (PSPME). Due to its surface chemistry, high surface area and capacity, PSPME provides significant increases in sensitivity over conventional fibre SPME. The results show a 50-400 times increase in the detection capacity for piperonal, the odour signature of 3,4 methylenedioxymethamphetamine (MDMA). The PSPME-IMS technique was able to detect 600 ng of piperonal in a 30 s extraction from a quart-sized can containing 5 MDMA tablets, while detection using fibre SPME-IMS was not attainable. In a blind study of six cases suspected to contain varying amounts of MDMA in the tablets, PSPME-IMS successfully detected five positive cases and also produced no false positives or false negatives. One positive case had minimal amounts of MDMA resulting in a false negative response for fibre SPME-IMS. PMID- 20355216 TI - Direct injection horse-urine analysis for the quantification and confirmation of threshold substances for doping control. IV. Determination of 3-methoxytyramine by hydrophilic interaction liquid chromatography/quadrupole time-of-flight mass spectrometry. AB - Levodopa and dopamine have been abused as performance-altering substances in horse racing. Urinary 3-methoxytyramine is used as an indicator of dopaminergic manipulation resulting from dopamine or levodopa administration and is prohibited with a urinary threshold of 4 microg mL(-1) (free and conjugated). A simple liquid chromatographic (LC)/mass spectrometric (MS) (LCMS) method was developed and validated for the quantification and identification of 3-methoxytyramine in equine urine. Sample preparation involved enzymatic hydrolysis and protein precipitation. Hydrophilic interaction liquid chromatography (HILIC) was selected as a separation technique that allows effective retention of polar substances like 3-methoxytyramine and efficient separation from matrix compounds. Electrospray ionization (ESI) in positive mode with product ion scan mode was chosen for the detection of the analytes. Quantification of 3-methoxytyramine was performed with fragmentation at low collision energy, resulting in one product ion, while a second run at high collision energy was performed for confirmation (at least three abundant ions). Studies on matrix effects showed ion suppression depending on the horse urine used. To overcome the variability of the results originating from the matrix effects, isotopic labelled internal standard was used and linear regression calibration methodology was applied for the quantitative determination of the analyte. The tested linear range was 1-20 microg mL(-1). The relative standard deviations of intra- and inter- assay analysis of 3 methoxytyramine in horse urine were lower than 4.2% and 3.2%, respectively. Overall accuracy (relative percentage error) was less than 6.2%. The method was applied to case samples, demonstrating simplicity, accuracy and selectivity. PMID- 20355217 TI - Detection and characterization of synthetic steroidal and non-steroidal anti inflammatory drugs in Indian ayurvedic/herbal products using LC-MS/TOF. AB - It is claimed that ayurvedic/herbal healthcare products (AHPs) are safe because of their natural origin. However, several reports exist of adulteration of AHPs with synthetic drugs. In this study, a generalized strategy was developed using LC-MS/TOF for the detection and verification of steroidal and anti-inflammatory drugs in 58 AHPs collected from various parts of India. The strategy involved recording of mass spectral information for standard drugs-including ionization mode (ESI/APCI - ve or + ve), mass spectrum, accurate mass, identification of qualifier fragments (two), extracted ion chromatograms (EICs), isotopic pattern and determination of UV max (nm)-through UV-PDA studies. Adulteration was then detected in AHPs primarily through comparison of EICs at accurate m/z for molecular ion peaks and R(T) matching with the standard. It was confirmed by spiking with the standards, and matching mass spectrum, accurate mass, R(T) of qualifier fragments, isotopic pattern and UV spectrum of the standards with the adulterant peaks in AHPs. Dexamethasone and diclofenac were detected as adulterants in ten AHPs whereas one AHP tested positive for piroxicam and another for dexamethasone. All the adulterated products were sold by the healthcare practitioners, while no product marketed by manufacturers or chemist shops had this problem. The study showed that LC-MS/TOF-based screening could be used as a rapid approach to monitor adulteration of steroids and anti-inflammatory drugs in AHPs. PMID- 20355218 TI - Comparison of the urinary protein patterns of athletes by 2D-gel electrophoresis and mass spectrometry-a pilot study. AB - Urinary proteins and exercise-induced proteinuria have been the subject of much research. Proteinuria has been studied in depth after different running and cycling intensities and durations and the different mechanisms of glomerular filtration and tubular dysfunction have been elucidated. The present study was carried out to compare urinary protein profiles of athletes in different sport categories (endurance sport, team sport, strength sport). Doping-control urine samples obtained from in-competition testing and specimens derived from a control group were analysed by means of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significantly deviating protein spots were enzymatically hydrolysed and identified by nanoflow liquid chromatography orbitrap mass spectrometry. Endurance sport samples demonstrated a significant increase of mainly medium-sized urinary proteins such as transferrin, zinc alpha 2-glycoprotein and prostaglandin H2 D-isomerase (30-80 kDa) in 2D-PAGE experiments. Proteinuria was evident in all samples after protein concentration measurements (protein/creatinine > 15 mg/mmol). Alterations were also observed in strength sport samples, which showed an increase of low molecular weight proteins or protein fragments (<30 kDa, e.g., transthyretin, CD 59 antigen or an N terminal transferrin fragment). In contrast, the concentration measurements did not imply proteinuria but total protein excretion was in a normal range. The study provides a first overview on 2D maps of the urinary proteome after different types of exercise. Future studies may lead to the establishment of urinary protein maps that are typical for a certain type of sport or even an individual athlete. These maps may complement the blood passport of athletes in doping control. PMID- 20355219 TI - Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. AB - Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine (also referred to as S-4, S 3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl) propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3 (4-nitro-3-trifluoromethyl-phenylamino)-propionamide. The ease of purchasing non approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key element of preventive doping research, limiting the options for cheating athletes who aim to undermine the doping control system. PMID- 20355220 TI - Growth hormone: barriers to the implementation of human growth hormone testing in sport. PMID- 20355221 TI - Unfair advantage: the importance to clean athletes of preventing HGH abuse in sport. PMID- 20355222 TI - Advancing the battle against human growth hormone. PMID- 20355223 TI - Is human growth hormone an ergogenic aid? AB - Growth hormone (GH) was first isolated from the pituitary gland in the 1940s. It is believed that athletes have been abusing GH for its anabolic and lipolytic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Most of our knowledge about GH abuse is anecdotal but a number of high-profile athletes have admitted using GH. Despite its widespread abuse, there is debate about whether GH is ergogenic. Indeed most scientific studies have not shown a performance enhancing effect. This review will address why this discrepancy of opinion between athletes and scientists exists and why the author believes that the scientists are wrong. PMID- 20355224 TI - Growth hormone and anabolic steroids: athletes are the tip of the iceberg. AB - Professional Athletes' misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and "anti-aging". Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors. PMID- 20355225 TI - Detecting growth hormone abuse in athletes. AB - There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although GH is on the World Anti-doping Agency (WADA) list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on the measurement of pituitary GH isoforms and the second is based on the measurement of markers of GH action.Pituitary GH contains multiple isoforms whereas recombinant human GH comprises solely the 22-kDa isoform. Immunoassays that recognize the different isoforms have been developed and form the basis of the test introduced by WADA at the Athens Olympic Games. To date, no athlete has tested positive.The GH-2000 project proposed a test based on the measurement of insulin-like growth factor-I (IGF-I) and type III pro-collagen (P III-P) as these markers increase in a dose-dependent manner in response to GH and their basal concentration varies much less than GH. When combined with discriminant function analysis, these markers were able to differentiate between those taking GH and placebo in double-blind placebo controlled trials. Subsequent studies have shown that the test is applicable across different ethnicities and is unaffected by injury. PMID- 20355226 TI - Legal issues arising out of blood testing for human growth hormone. PMID- 20355227 TI - Issues of testing for hGH: collection. AB - Urine has limitations as a substrate for anti-doping efforts and within the last decade sports organizations have begun collecting blood samples in cooperation with anti-doping laboratories. Within the US, authorization to perform a blood draw is determined by the scope-of-practice licensure regulations in each state. Blood collection requires equipment not necessary in standard anti-doping urine collections. There is a need for greater privacy and cleanliness than the usual site for urine collection provides. One of the most challenging aspects of a blood collection is complying with the guidelines for specimen transport. In addition to the standard chain-of-custody protocols that collectors must follow for urine, blood samples call for additional handling to ensure they arrive at the anti-doping laboratory in a condition that allows for analysis. While the invasiveness of the process increases liability risk to the collector, following established standards, guidelines and anti-doping protocols will minimize risk. One significant advantage of blood over urine in anti-doping settings is that specimen adulteration or manipulation is nearly impossible. Therefore, for blood only collections, sports organizations should explore opportunities for collaboration with the American Red Cross or private blood-collection centres/clinics. PMID- 20355228 TI - Regulatory implications for the use of pharmaceutical markers to improve the detection of human growth hormone. PMID- 20355229 TI - Enrichment and immunoprecipitation of 22 kDa human growth hormone spiked into human urine. AB - Approaches to detect whether an athlete has used growth hormone have been intensely investigated by sport organizations for 20 years. This effort has led to a human growth hormone (hGH) isoform ratio test in serum that has been approved by WADA and deployed at three Olympic Games, although a positive case has yet to be reported. We set out to determine whether the ratio test could be applied to urine. First we investigated various ways to extract hGH from spiked urine. We were able to recover 95% using selective centrifugal concentration. This fraction was then subjected to four different commercially available immunoprecipitation kits. The highest yield was obtained with the Invitrogen Dynabeads Protein G kit. Nevertheless it is apparent that these methods do not recover enough hGH for subsequent analysis by mass spectrometry. With further effort greater recovery of the 22 kDa isoform might be achieved, however it is very unlikely that the 20 kDa isoform could be detected. This method may be significantly improved by the application of both nanoparticle and aptamer technology. PMID- 20355231 TI - Growth hormone: barriers to the implementation of human growth hormone testing in sport. Interview by Paul Trevorrow. PMID- 20355230 TI - Nanoparticle technology: amplifying the effective sensitivity of biomarker detection to create a urine test for hGH. AB - Several clinical-grade immunoassays exist for the specific measurement of hGH or its isoforms in blood but there is an urgent need to apply these same reliable assays to the measurement of hGH in urine as a preferred 'non-invasive' biofluid. Unfortunately, conventional hGH immunoassays cannot attain the sensitivity required to detect the low concentrations of hGH in urine. The lowest limit of sensitivity for existing hGH immunoassays is >50 pg/mL, while the estimated concentration of urinary hGH is about 1 pg/m-50 times lower than the sensitivity threshold. We have created novel N-isopropylacrylamide (NIPAm)-based hydrogel nanoparticles functionalized with an affinity bait. When introduced into an analyte-containing solution, the nanoparticles can perform, in one step, (1) complete harvesting of all solution phase target analytes, (2) full protection of the captured analyte from degradation and (3) sequestration of the analyte, effectively increasing the analyte concentration up to a hundredfold. N isopropylacrylamide nanoparticles functionalized with Cibacron Blue F3GA bait have been applied to raise the concentration of urinary hGH into the linear range of clinical grade immunoassays. This technology now provides an opportunity to evaluate the concentration of hGH in urine with high precision and accuracy. PMID- 20355232 TI - Ezetimbe as potential treatment for cholesterol gallstones: the need for clinical trials. AB - Obesity is associated with insulin resistance, non-alcoholic fatty liver disease (NAFLD) and gallstones.High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but also NAFLD and insulin resistance. Interestingly, a high incidence of gallstones is being reported in association with insulin resistance and NAFLD. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallbladder disease. Ezetimibe is a drug that inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Importantly, ezetimibe showed potential benefit not only in treating and preventing gallstones but also in insulin resistance and NAFLD. Further studies are required before the use of ezetimibe for the treatment of gallstones can be advocated. PMID- 20355233 TI - Liver magnetic resonance imaging: State of the art. PMID- 20355234 TI - Liver fat content determined by magnetic resonance imaging and spectroscopy. AB - Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fat-containing vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the invasive technique, various other non invasive techniques have been developed, such as ultrasound, computed tomography (CT), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) based methods. Among these techniques, ultrasound and CT provide only qualitative information about hepatic steatosis, whereas MRS- or MRI-based methods are able to determine even small amounts of fat accurately. These non-invasive magnetic resonance techniques have already proven their great potential, especially in longitudinal and cross-sectional studies regarding various metabolic conditions and medical treatment regimens. In this review, the most common, non-invasive MRS/MRI techniques for assessment of intrahepatic lipid content are described with their inherent advantages and limitations. PMID- 20355235 TI - Diffusion weighted imaging in the liver. AB - Diffusion weighted magnetic resonance imaging (DWI) is an imaging technique which provides tissue contrast by the measurement of diffusion properties of water molecules within tissues. Diffusion is expressed in an apparent diffusion coefficient (ADC), which reflects the diffusion properties unique to each type of tissue. DWI has been originally used in neuroradiology. More recently, DWI has increasingly been used in addition to conventional unenhanced and enhanced magnetic resonance imaging (MRI) in other parts of the body. The reason for this delay was a number of technical problems inherent to the technique, making DWI very sensitive to artifacts, which had to be overcome. With assessment of ADC values, DWI proved to be helpful in characterization of focal liver lesions. However, DWI should always be used in conjunction to conventional MRI since there is considerable overlap between ADC values of benign and malignant lesions. DWI is useful in the detection of hepatocellular carcinoma in the cirrhotic liver and detection of liver metastases in oncological patients. In addition, DWI is a promising tool in the prediction of tumor responsiveness to chemotherapy and the follow-up of oncological patients after treatment, as DWI may be capable of detecting recurrent disease earlier than conventional imaging. This review focuses on the most common applications of DWI in the liver. PMID- 20355236 TI - Magnetic resonance spectroscopy to study hepatic metabolism in diffuse liver diseases, diabetes and cancer. AB - This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used as a research tool rather than a clinical tool. The liver is particularly suitable for static and dynamic metabolic studies due to its high metabolic activity. Furthermore, its relatively superficial position allows excellent MRS localization, while its large volume allows detection of signals with relatively low intensity. This review describes the application of MRS to study the metabolic consequences of different conditions including diffuse and chronic liver diseases, congenital diseases, diabetes, and the presence of a distant malignancy on hepatic metabolism. In addition, future prospects of MRS are discussed. It is anticipated that future technical developments such as clinical MRS magnets with higher field strength (3 T) and improved delineation of multi-component signals such as phosphomonoester and phosphodiester using proton decoupling, especially if combined with price reductions for stable isotope tracers, will lead to intensified research into metabolic syndrome, cardiovascular disease, hepato biliary diseases, as well as non-metastatic liver metabolism in patients with a distant malignant tumor. PMID- 20355237 TI - Liver iron content determination by magnetic resonance imaging. AB - Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately reflects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer. PMID- 20355238 TI - Perfusion magnetic resonance imaging of the liver. AB - Perfusion magnetic resonance imaging (MRI) studies quantify the microcirculatory status of liver parenchyma and liver lesions, and can be used for the detection of liver metastases, assessing the effectiveness of anti-angiogenic therapy, evaluating tumor viability after anti-cancer therapy or ablation, and diagnosis of liver cirrhosis and its severity. In this review, we discuss the basic concepts of perfusion MRI using tracer kinetic modeling, the common kinetic models applied for analyses, the MR scanning techniques, methods of data processing, and evidence that supports its use from published clinical and research studies. Technical standardization and further studies will help to establish and validate perfusion MRI as a clinical imaging modality. PMID- 20355239 TI - Techniques for colorectal anastomosis. AB - Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety aspects of anastomosis and alternatives to hand-sewn and stapled techniques are being sought. Here, we review alternative anastomotic techniques used to fashion bowel anastomosis. Compression anastomosis using compression anastomotic clips, endoluminal compression anastomotic rings, AKA-2, biofragmental anastomotic rings, or Magnamosis all involve the concept of creating a sutureless end-to-end anastomosis by compressing two bowel ends together, leading to a simultaneous necrosis and healing process that joins the two lumens. Staple line reinforcement is a new approach that reduce the drawbacks of staplers used in colorectal practice, i.e. leakage, bleeding, misfiring, and inadequate tissue approximation. Various non-absorbable, semi or fully absorbable materials are now available. Two other techniques can provide alternative anastomotic support to the suture line: a colorectal drain and a polyester stent, which can be utilized in ultra-low rectal excision and can negate the formation of a defunctioning stoma. Doxycycline coated sutures have been used to overcome the post-operative weakness in anastomosis secondary to rapid matrix degradation mediated by matrix metalloproteinase. Another novel technique, the electric welding system, showed promising results in construction of a safe, neat, smooth sutureless bowel anastomosis. Various anastomotic techniques have been shown to be comparable to the standard techniques of suturing and stapling. However, most of these alternatives need to be accepted and optimized for future use. PMID- 20355240 TI - Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis. AB - AIM: To investigate the potential therapeutic effect of exopolysaccharide (EPS) producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice. METHODS: Balb/c mice were fed with the fermented milk for 7 d after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for 10 d). Omeprazole was included in this study as a positive therapeutic control. The gastric inflammatory activity was evaluated from gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-gamma (INFgamma) and tumor necrosis factor-alpha (TNF-alpha) cytokine producing cells in the gastric mucosa, and thickness of the mucus layer. RESULTS: Animals receiving treatment with the EPS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. Inflammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 + or - 0.03 vs 2.0 + or - 0.6, P < 0.05). A marked decrease in INFgamma(+) (15 + or - 1.0 vs 28 + or - 1.2, P < 0.05) and TNF-alpha(+) (16 + or - 3.0 vs 33 + or - 3.0, P < 0.05) cells and an increase in IL-10(+) (28 + or - 1.5 vs 14 + or - 1.3, P < 0.05) cells compared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 + or - 0.6 vs 1.0 + or - 0.3; 5.1 + or - 0.8 vs 1.5 + or - 0.4 in the corpus and antrum mucosa, respectively, P < 0.05) compared with the gastritis group was noted. A milk suspension of the purified EPS from S. thermophilus CRL1190 was also effective as therapy for gastritis. CONCLUSION: This study suggests that fermented milk with S. thermophilus CRL 1190 and/or its EPS could be used in novel functional foods as an alternative natural therapy for chronic gastritis induced by ASA. PMID- 20355242 TI - Hepatic osteodystrophy and liver cirrhosis. AB - AIM: To investigate the correlation between hepatic osteodystrophy and osteoporosis in patients with liver cirrhosis. METHODS: Bone mineral density of the patients (n = 55) and that of the control group (n = 30) were measured by dual-energy X-ray absorptiometry. All the women in the study were premenopausal. Deoxypyridinoline, pyridinoline and urinary Ca(2+) were measured as bone destruction markers, while alkaline phosphatase (ALP), osteocalcin and insulin like growth factor-1 (IGF-1) were measured as bone formation markers. Furthermore, interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-alpha), vitamin D3, direct bilirubin, albumin, cortisol and parathyroid hormone (PTH) levels were measured. The independent Student t test and chi(2) test were employed in comparing both groups, and the Pearson correlation test was used to determine associations. RESULTS: Comparing cirrhosis and control groups, lumbar total T-score (-1.6 + or - 1.2 g/cm(2) vs -0.25 + or - 1.3 g/cm(2), P < 0.001), lumbar total Z-score (-1.2 + or - 1.23 g/cm(2) vs -0.6 + or - 1.3 g/cm(2), P < 0.001), total femur T-score (-0.05 + or - 1 g/cm(2) vs -0.6 + or - 0.9 g/cm(2), P = 0.003) and total femur Z-score (-0.08 + or - 1.5 g/cm(2) vs 0.7 + or - 0.9 g/cm(2), P = 0.003) showed significantly lower values in the cirrhosis group. Blood ALP level (109.2 + or - 57 U/L vs 62.6 + or - 32.5 U/L, P < 0.001), IL-6 level (27.9 + or - 51.6 pg/mL vs 3.3 + or - 3.1 pg/mL, P = 0.01), TNF-alpha level (42.6 + or - 33.2 pg/mL vs 25.3 + or - 12.3 pg/mL, P = 0.007) and direct bilirubin level (0.9 + or - 0.7 mg/dL vs 0.3 + or - 0.2 mg/dL, P < 0.001) were significantly higher in the cirrhosis group. IGF-1 level (47.7 + or - 26.2 ng/mL vs 143.4 + or - 53.2 ng/mL, P < 0.001), osteocalcin level (1.05 + or - 2.5 ng/mL vs 7.0 + or - 13 ng/mL, P = 0.002) and 24 h urinary Ca(2+) (169.6 + or - 227.2 mg/dL vs 287 + or - 168.6 mg/dL, P = 0.003) were significantly lower in the cirrhosis group. Urinary deoxypyridinoline/creatinine (9.4 + or - 9.9 pmol/micromol vs 8.1 + or - 5.3 pmol/micromol, P = 0.51), urinary pyridinoline/creatinine (51.3 + or - 66.6 pmol/micromol vs 29 + or - 25.8 pmol/micromol, P = 0.08), blood IL-1 level (3.4 + or - 8.8 pg/mL vs 1.6 + or - 3.5 pg/mL, P = 0.29), vitamin D3 level (18.6 + or - 13.3 microg/L vs 18.4 + or - 8.9 microg/L, P = 0.95), cortisol level (11.1 + or - 4.8 microg/dL vs 12.6 + or - 4.3 microg/dL, P = 0.15) and PTH level (42.7 + or - 38 microg/dL vs 34.8 + or - 10.9 microg/dL, P = 0.27) were not significantly different. CONCLUSION: Hepatic osteodystrophy is an important complication encountered in patients with liver cirrhosis and all patients should be monitored for hepatic osteodystrophy. PMID- 20355241 TI - Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma. AB - AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% + or - 0.49% and 72.5% + or - 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy. PMID- 20355243 TI - Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. AB - AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa (chi(2) = 9.999, P = 0.002). LRP16 protein expression was found in 43.3% (52/120) of carcinoma at stage I and II, and 80.2% (65/81) of carcinoma at stage III and IV (chi(2) =27.088, P = 0.001). Correlation between LRP16 expression and clinicopathological factors was significant in differentiation (P = 0.010), tumor size (P = 0.001), infiltrative depth (P = 0.000) and distant metastasis (P = 0.027). The difference of median survival time between cancer patients with LRP16 expression (38.0 mo) and those without was statistically significant (105.0 mo, Log rank = 41.455, P = 0.001). The multivariate survival analysis revealed that LRP16 expression was correlated significantly (Cox's regression: P = 0.001, relative risk = 2.082) with shortened survival in the patients with colorectal cancer. CONCLUSION: The expression of LRP16 is related to the degree of differentiation, invasiveness, metastasis and prognosis of colorectal carcinoma. PMID- 20355244 TI - Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. AB - AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage II-III) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-, 5- and 10-year survival were followed up. Progression-free survival (PFS) was chosen as the primary endpoint by treatment arm measured from study entry until documented progression of disease or death from any cause. The secondary endpoint was overall survival (OS) determined as the time (in months) between the date of therapy and the date of death. Other objectives were surgical and adjuvant therapy complications. RESULTS: With median follow-up of 45 mo for all the enrolled patients, significant differences in the 1-, 3-, 5-, 10-year OS (91.3%, 63.5%, 43.5%, 24.5% vs 91%, 62.8%, 42.3%, 24.4% vs 87.5%, 51.3%, 33.8%, 12.5%, P = 0.0176) and PFS (89.3%, 61.3%, 37.5%, 18.1% vs 89.1%, 61.1%, 37.2%, 17.8% vs 84.5%, 49.3%, 25.9%, 6.2%, P = 0.0151) were detected among the 3 arms. There were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). For the patients who had radical resection, significant differences in median PFS (48 mo vs 61 mo vs 39.5 mo, P = 0.0331) and median OS (56.5 mo vs 72 mo vs 41.5 mo, P = 0.0153) were detected among the 3 arms, but there were no significant differences in OS and PFS between the preoperative CRT and postoperative CRT arm (P > 0.05). The local recurrence rates in the preoperative CRT, postoperative CRT group and S group were 11.3%, 14.1% and 35%, respectively (P < 0.05). No significant differences were detected among the 3 groups when comparing complications but tended to be in favor of the postoperative CRT and S groups (P > 0.05). Toxicities of CRT in the preoperative or postoperative CRT arms were mostly moderate, and could be quickly alleviated by adequate therapy. CONCLUSION: Rational application of preoperative or postoperative CRT can provide a benefit in PFS and OS in patients with locally advanced ESCC. PMID- 20355245 TI - Double-balloon enteroscopy for obscure gastrointestinal bleeding: a single center experience in China. AB - AIM: To evaluate the diagnostic value of double-balloon enteroscopy (DBE) for obscure gastrointestinal bleeding (OGIB). METHODS: The data about 75 OGIB patients who underwent DBE in January 2007-June 2009 in our hospital were retrospectively analyzed. RESULTS: DBE was successfully performed in all 75 patients without complication. Of the 75 patients, 44 (58.7%) had positive DBE findings, 22 had negative DBE findings but had potential bleeding at surgery and capsule endoscopy, etc. These 66 patients were finally diagnosed as OGIB which was most commonly caused by small bowel tumor (28.0%), angiodysplasia (18.7%) and Crohn's disease (10.7%). Lesions occurred more frequently in proximal small bowel than in distal small bowel (49.3% vs 33.3%, P = 0.047). CONCLUSION: DBE is a safe, effective and accurate procedure for the diagnosis of OGIB. PMID- 20355246 TI - Porcine hepatocyte isolation and reversible immortalization mediated by retroviral transfer and site-specific recombination. AB - AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40Tag). METHODS: We first established a method of porcine hepatocyte isolation with a modified four-step retrograde perfusion technique. Then the porcine hepatocytes were immortalized with retroviral vector SSR#69 expressing SV40T and hygromycin-resistance genes flanked by paired loxP recombination targets. SV40T cDNA in the expanded cells was subsequently excised by Cre/LoxP site-specific recombination. RESULTS: The resultant hepatocytes with high viability (97%) were successfully immortalized with retroviral vector SSR#69. One of the immortalized clones showed the typical morphological appearance, TJPH-1, and was selected by clone rings and expanded in culture. After excision of the SV40T gene with Cre-recombinase, cells stopped growing. The population of reverted cells exhibited the characteristics of differentiated hepatocytes. CONCLUSION: In conclusion, we herein describe a modified method of hepatocyte isolation and subsequently established a porcine hepatocyte cell line mediated by retroviral transfer and site-specific recombination. PMID- 20355247 TI - Over-the-scope clip closure of two chronic fistulas after gastric band penetration. AB - Gastrointestinal perforations are conservatively managed at endoscopy by through the-scope endoclips and covered self expandable stents, according to the size and tissue features of the perforation. This is believed to be the first report of successful closure of two gastro-cutaneous fistulas with over-the-scope clips (OTSCs). After laparoscopic gastric banding, a 45-year old woman presented with band erosion and penetration. Despite surgical band removal and gastric wall suturing, external drainage of enteric material persisted for 2 wk, and esophagogastroduodenoscopy demonstrated two adjacent 10-mm and 15-mm fistulous orifices at the esophagogastric junction. After cauterization of the margins, the 10-mm fistulous tract was grasped by the OTSC anchor, invaginated into the applicator cap, and closed by a traumatic OTSC. The other 15-mm fistula was too large to be firmly grasped, and a fully-covered metal stent was temporarily placed. No leak occurred during the following 6 wk. At stent removal: the OTSC was completely embedded in hyperplastic overgrowth; the 15-mm fistula significantly reduced in diameter, and it was closed by another traumatic OTSC. After the procedure, no external fistula recurred and both OTSCs were lost spontaneously after 4 wk. The use of the anchor and the OTSC seem highly effective for successful closure of small chronic perforations. PMID- 20355248 TI - Therapeutic angiography for giant bleeding gastro-duodenal artery pseudoaneurysm. AB - We present the case of an 18-year-old female transferred to our center from an outside hospital due to persistent gastrointestinal bleeding. Two weeks prior to her transfer she underwent duodenal omentopexy for a perforated duodenal peptic ulcer. The patient underwent a computed tomography angiogram which identified the source of bleeding as a giant gastro-duodenal artery (GDA) pseudoaneurysm. The patient was taken to interventional radiology where successful microcoil embolization was performed. We present this rare case of a giant GDA pseudoaneurysm together with imaging and a review of the medical literature regarding prevalence, etiology and treatment options for visceral arterial aneurysms. PMID- 20355249 TI - A geriatric patient with diffuse idiopathic skeletal hyperostosis. AB - The most frequent health problems seen in senility are chronic and degenerative diseases. A 75-year-old male patient with the complaints of weight loss and difficulty in swallowing was admitted to our hospital from a nursing home. Upper system fiber-optic gastrointestinal endoscopy was performed and a mass at the junction of the hypopharynx and esophagus just below recessus piriformis obstructing almost the whole of the lumen and blocking the distal passage was detected. Computed tomography revealed marked narrowing secondary to osseous hypertrophy in the air column of the hypopharynx and proximal esophagus. Diffuse idiopathic skeletal hyperostosis or Forestier's disease is an idiopathic disease characterized by the ossification of the anterior longitudinal ligament of vertebra and some of the extraspinal ligaments. In the present case we aim to discuss an elderly patient who suffered from dysphagia and weight loss and the diagnostic stages. PMID- 20355250 TI - Peeling a giant ileal lipoma with endoscopic unroofing and submucosal dissection. AB - Lipoma is relatively common in the colon but is less often in the small intestine. Most lipomas are incidentally detected at endoscopy and are usually small and asymptomatic. However, some of them can present with obstruction and/or intussusceptions. Surgical resection is commonly recommended to remove such significant lipomas with a limited pedicle and larger than 2 cm in size, as endoscopic resection may result in unfavorable complications such as intestinal perforations. We report a case of 62-year-old man presenting with hematochezia. Colonoscopy showed a submucosal tumor, about 50 mm in size, in the terminal ileum. A clinical diagnosis of lipoma was established based on the findings of colonoscopy and abdominal computed tomography (CT). As the patient complained of hematochezia and mild iron deficiency anemia associated with repeated tumor prolapse, we decided to remove his lipoma. Consequently, the lesion was completely removed en bloc. Although abdominal CT immediately after removal of the lesion showed a small amount of free air, conservative treatment was successfully carried out for the perforation. Histologically, the removed lesion was a lipoma. PMID- 20355251 TI - Upper gastrointestinal hemorrhage caused by superwarfarin poisoning. AB - Superwarfarins are a class of rodenticides. Gastrointestinal hemorrhage is a fatal complication of superwarfarin poisoning, requiring immediate treatment. Here, we report a 55-year-old woman with tardive upper gastrointestinal hemorrhage caused by superwarfarin poisoning after endoscopic cold mucosal biopsy. PMID- 20355252 TI - What are the hallmarks of cancer? AB - The seminal article by Douglas Hanahan and Robert Weinberg on the hallmarks of cancer is 10 years old this year and its contribution to how we see cancer has been substantial. But, in embracing this view, have we lost sight of what makes cancer cancer? PMID- 20355253 TI - Identification of a hybrid PKS-NRPS required for the biosynthesis of NG-391 in Metarhizium robertsii. AB - The fungal entomopathogen Metarhizium robertsii (formerly known as M. anisopliae var. anisopliae) is a prolific producer of secondary metabolites of which very little is known at the genetic level. To establish the genetic bases for the biosynthesis of the mutagenic compound NG- 391, we identified a 19,818 kb genomic region harboring the predicted hybrid polyketide synthase-nonribosomal peptide synthetase NGS1, plus five additional ORFs. NGS1 knockouts generated by Agrobacterium-mediated transformation failed to produce detectable levels of NG 391, indicating the involvement of this locus in its biosynthesis. NGS1 deletion mutants had no significant changes in virulence levels against larvae of Spodoptera exigua and in resistance to hydrogen peroxide-generated oxidative stress compared to the wild-type strain. All 6 ORFs were expressed in medium supporting production of NG-391, and NGS1 was expressed during the interaction with the S. exigua host. The use of an NGS1 promoter-GFP reporter fusion showed that during in vitro growth in still broth cultures, NGS1 expression is restricted to the early exponential phase and is affected by M. robertsii cell density. PMID- 20355254 TI - Arctic acid test. PMID- 20355255 TI - Whaling battles. PMID- 20355256 TI - New climate change scenarios. PMID- 20355257 TI - Interview with Michael Hastings. PMID- 20355258 TI - Genome scan of hybridizing sunflowers from Texas (Helianthus annuus and H. debilis) reveals asymmetric patterns of introgression and small islands of genomic differentiation. AB - Although the sexual transfer of genetic material between species (i.e. introgression) has been documented in many groups of plants and animals, genome wide patterns of introgression are poorly understood. Is most of the genome permeable to interspecific gene flow, or is introgression typically restricted to a handful of genomic regions? Here, we assess the genomic extent and direction of introgression between three sunflowers from the south-central USA: the common sunflower, Helianthus annuus ssp. annuus; a near-endemic to Texas, Helianthus debilis ssp. cucumerifolius; and their putative hybrid derivative, thought to have recently colonized Texas, H. annuus ssp. texanus. Analyses of variation at 88 genetically mapped microsatellite loci revealed that long-term migration rates were high, genome-wide and asymmetric, with higher migration rates from H. annuus texanus into the two parental taxa than vice versa. These results imply a longer history of intermittent contact between H. debilis and H. annuus than previously believed, and that H. annuus texanus may serve as a bridge for the transfer of alleles between its parental taxa. They also contradict recent theory suggesting that introgression should predominantly be in the direction of the colonizing species. As in previous studies of hybridizing sunflower species, regions of genetic differentiation appear small, whether estimated in terms of FST or unidirectional migration rates. Estimates of recent immigration and admixture were inconsistent, depending on the type of analysis. At the individual locus level, one marker showed striking asymmetry in migration rates, a pattern consistent with tight linkage to a Bateson-Dobzhansky-Muller incompatibility. PMID- 20355259 TI - Competitive PCR reveals the complexity of postcopulatory sexual selection in Teleogryllus commodus. AB - The outcome of mate choice depends on complex interactions between males and females both before and after copulation. Although the competition between males for access to mates and premating choice by females are relatively well understood, the nature of interactions between cryptic female choice and male sperm competition within the female reproductive tract is less clear. Understanding the complexity of postcopulatory sexual selection requires an understanding of how anatomy, physiology and behaviour mediate sperm transfer and storage within multiply mated females. Here we use a newly developed molecular technique to directly quantify mixed sperm stores in multiple mating females of the black field cricket, Teleogryllus commodus. In this species, female postcopulatory choice is easily observed and manipulated as females delay the removal of the spermatophore in favour of preferred males. Using twice-mated females, we find that the proportion of sperm in the spermatheca attributed to the second male to mate with a female (S2) increases linearly with the time of spermatophore attachment. Moreover, we show that the insemination success of a male increases with its attractiveness and decreases with the size of the female. The effect of male attractiveness in this context suggests a previously unknown episode of mate choice in this species that reinforces the sexual selection imposed by premating choice and conflicts with the outcome of postmating male harassment. Our results provide some of the clearest evidence yet for how sperm transfer and displacement in multiply mated females can lead directly to cryptic female choice, and that three distinct periods of sexual selection operate in black field crickets. PMID- 20355260 TI - Predisposing characteristics, enabling resources and need as predictors of utilization and clinical outcomes for veterans receiving mental health services. AB - BACKGROUND: Though demand for mental health services (MHS) among US veterans is increasing, MHS utilization per veteran is decreasing. With health and social service needs competing for limited resources, it is important to understand the association between patient factors, MHS utilization, and clinical outcomes. OBJECTIVES: We use a framework based on Andersen's behavioral model of health service utilization to examine predisposing characteristics, enabling resources, and clinical need as predictors of MHS utilization and clinical outcomes. METHODS: This was a prospective observational study of veterans receiving inpatient or outpatient MHS through Veterans Administration programs. Clinician ratings (Global Assessment of Functioning [GAF]) and self-report assessments (Behavior and Symptom Identification Scale-24) were completed for 421 veterans at enrollment and 3 months later. Linear and logistic regression analyses were conducted to examine: (1) predisposing characteristics, enabling resources, and need as predictors of MHS inpatient, residential, and outpatient utilization and (2) the association between individual characteristics, utilization, and clinical outcomes. RESULTS: Being older, female, having greater clinical need, lack of enabling resources (employment, stable housing, and social support), and easy access to treatment significantly predicted greater MHS utilization at 3-month follow-up. Less clinical need and no inpatient psychiatric hospitalization predicted better GAF and Behavior and Symptom Identification Scale-24 scores. White race and residential treatment also predicted better GAF scores. Neither enabling resources, nor number of outpatient mental health visits predicted clinical outcomes. CONCLUSIONS: This application of Andersen's behavioral model of health service utilization confirmed associations between some predisposing characteristics, need, and enabling resources on MHS utilization but only predisposing characteristics, need, and utilization were associated with clinical outcomes. PMID- 20355261 TI - Revisiting the cost-effectiveness of the COMBINE study for alcohol dependent patients: the patient perspective. AB - OBJECTIVE: Most cost and cost-effectiveness studies of substance abuse treatments focus on the costs to the provider/payer. Although this perspective is important, the costs incurred by patients should also be considered when evaluating treatment. This article presents estimates of patients' costs associated with the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) alcohol treatments and evaluates the treatments' cost-effectiveness from the patient perspective. STUDY DESIGN: A prospective cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial of 9 alternative alcohol treatment regimens involving 1383 patients with diagnoses of primary alcohol dependence across 11 US clinic sites. We followed a microcosting approach that allowed estimation of patients' costs for specific COMBINE treatment activities. The primary clinical outcomes from COMBINE are used as indicators of treatment effectiveness. RESULTS: The average total patient time devoted to treatment ranged from about 30 hours to 46 hours. Time spent traveling to and from treatment sessions and participation in self-help meetings accounted for the largest portion of patient time costs. The cost-effectiveness results indicate that 6 of the 9 treatments were economically dominated and only 3 treatments are potentially cost-effective depending on patient's willingness to pay for the considered outcomes: medical management (MM) + placebo, MM + naltrexone, and MM + naltrexone + acamprosate. CONCLUSIONS: Few studies consider the patient's perspective in estimating costs and cost-effectiveness even though these costs may have a substantial impact on a patient's treatment choice, ability to access treatment, or treatment adherence. For this study, the choice of the most cost effective treatment depends on the value placed on the outcomes by the patient, and the conclusions drawn by the patient may differ from that of the provider/payer. PMID- 20355262 TI - Nonoperative care for hip fracture in the elderly: the influence of race, income, and comorbidities. AB - CONTEXT: Hip fracture occurs in 340,000 older adults each year. Operative repair is the standard of care, maximizing the chances of functional recovery. Not receiving operative care may condemn patients to a lifetime of pain and potential immobility. OBJECTIVE: To measure the incidence of nonoperative treatment for first-time hip fracture in a population-based cohort and to measure the odds of nonoperative treatment of hip fracture among patients of differing race and income. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 165,861 Medicare beneficiaries admitted for hip fracture between March 31, 2002 and December 31, 2006 to hospitals in New York, Illinois, and Texas. MAIN OUTCOME MEASURES: Odds of nonoperative management of hip fracture, adjusted for fracture characteristics, comorbidities, source of admission, age, sex, race, income, and individual hospital effects. RESULTS: Nonoperative management occurred in 6.2% of patients (N = 10,283). After adjustment, black patients had a 79% increase in the odds of nonoperative management as compared with whites (OR 1.79, 95% CI 1.64 1.95). Low income itself was not associated with a change in the odds of nonoperative care. Among patients not receiving operative repair, blacks demonstrated lower mortality than whites at 7 days (7.96% vs. 20.17%, P < 0.0001) and 30 days (24.14% vs. 38.22%, P < 0.0001). CONCLUSIONS: Black race predicts an increased odds of nonoperative care for hip fracture. Among patients receiving nonoperative care, black patients demonstrated increased survival compared with whites. These results are consistent with differential selection of operative candidates by patient race. PMID- 20355263 TI - Differences in the diagnosis and management of type 2 diabetes in 3 countries (US, UK, and Germany): results from a factorial experiment. AB - OBJECTIVES: This article examines the diagnosis and management of type-2 diabetes when exactly the same "patient" is encountered by 192 randomly selected primary care doctors in 3 different health care systems--the United States, United Kingdom, and Germany. METHODS: We conducted a factorial experiment, employing 2 clinically authentic filmed scenarios, to examine country differences in the treatment of diabetes, while controlling the effects of selected characteristics of patients and physicians. The patient in the first scenario presented with (undiagnosed) signs and symptoms strongly suggestive of diabetes, while the second scenario presented an already diagnosed patient with an emerging foot neuropathy. Physicians were asked how they would diagnose and manage the patients after watching the video vignettes using a questionnaire with standardized and open-ended questions. RESULTS: Regarding the first (undiagnosed) case, US doctors would ask significantly more questions than physicians from the UK and Germany (P < 0.001). German physicians would give less advice but would want to see the patient again much sooner (P < 0.001). Regarding the diagnosed case with an emerging foot neuropathy, US physicians would be most active in terms of questioning, testing, prescribing, and advice giving. Again, physicians from Germany would be less active in terms of therapeutic strategies but they would like to see the patient again sooner (P = 0.005). CONCLUSIONS: Although physicians in the 3 countries encountered exactly the same patient, differences in diagnostic and management decisions were evident. The experimental design provides unconfounded estimates of health system differences while simultaneously controlling for the effects of selected patient attributes and physician characteristics. PMID- 20355264 TI - Clinical complexity in middle-aged and older adults with diabetes: the Health and Retirement Study. AB - BACKGROUND: Some patients with diabetes may have health status characteristics that could make diabetes self-management (DSM) difficult and lead to inadequate glycemic control, or limit the benefit of some diabetes management interventions. OBJECTIVE: To investigate how many older and middle-aged adults with diabetes have such health status characteristics. DESIGN: Secondary data analysis of a nationally representative health interview survey, the Health and Retirement Study, and its diabetes mail-out survey. SETTING/PARTICIPANTS: Americans aged 51 and older with diabetes (n = 3506 representing 13.6 million people); aged 56 and older in diabetes survey (n = 1132, representing 9.9 million). MEASUREMENTS: Number of adults with diabetes and (a) relatively good health; (b) health status that could make DSM difficult (eg, comorbidities, impaired instrumental activities of daily living; and (c) characteristics like advanced dementia and activities of daily living dependency that could limit benefit of some diabetes management. Health and Retirement Study measures included demographics. Diabetes Survey included self-measured HbA1c. RESULTS: Nearly 22% of adults > or =51 with diabetes (about 3 million people) have health characteristics that could make DSM difficult. Another 10% (1.4 million) may receive limited benefit from some diabetes management. Mail-out respondents with health characteristics that could make DSM difficult had significantly higher mean HbA1c compared with people with relatively good health (7.6% vs. 7.3%, P < 0.04.). CONCLUSIONS: Some middle-aged as well as older adults with diabetes have health status characteristics that might make DSM difficult or of limited benefit. Current diabetes quality measures, including measures of glycemic control, may not reflect what is possible or optimal for all patient groups. PMID- 20355266 TI - Using instrument-defined health state transitions to estimate minimally important differences for four preference-based health-related quality of life instruments. AB - OBJECTIVE: To estimate minimally important differences (MIDs) for the EQ-5D, Health Utilities Index Mark II (HUI2), HUI3, and SF-6D health index scores using health-state transitions defined by each instrument's multiattribute health classification (MAHC) system. METHODS: We assume that changes in preference scores associated with the smallest health transitions defined by an MAHC system are minimally important. Any transitions between 2 health states defined by an MAHC system which differ in only one health dimension or attribute and by only one functional level are considered "smallest health transitions." Thus, each such health transition provides 1 MID estimate. The MID for each of the 4 instruments was estimated using all the hypothetical smallest health transitions defined by its MAHC system. RESULTS: Based on our definitions, the total number of smallest health transitions was 405 for the EQ-5D, 127,600 for the HUI2, 6,382,800 for the HUI3, and 86,700 for the SF-6D. The mean (standard deviation) MID estimate was 0.040 (0.026) for the EQ-5D (US algorithm), 0.082 (0.032) for the EQ-5D (UK algorithm), 0.045 (0.039) for the HUI2, 0.032 (0.027) for the HUI3, and 0.027 (0.028) for the SF-6D. The effect sizes of these MID estimates ranged from 0.11 to 0.37. These MID estimates are quite comparable to published values estimated from empirical data using anchor-based methods. CONCLUSIONS: It is possible to use health transitions defined by the MAHC system to estimate the MIDs for preference-based health index scores. This study provides new information regarding MID estimates for the 4 health indices examined. PMID- 20355265 TI - Factors that influence practitioners' interpretations of evidence from alternative medicine trials: a factorial vignette experiment embedded in a national survey. AB - BACKGROUND: Clinical trial evidence in controversial areas such as complementary and alternative medicine (CAM) must be approached with an open mind. OBJECTIVE: To determine what factors may influence practitioners' interpretation of evidence from CAM trials. RESEARCH DESIGN: In a mailed survey of 2400 US CAM and conventional medicine practitioners we included 2 hypothetical factorial vignettes of positive and negative research results for CAM clinical trials. Vignettes contained randomly varied journal (Annals of Internal Medicine vs. Journal of Complementary and Alternative Medicine) and CAM treatment type (acupuncture, massage, glucosamine, meditation, and reiki). Response items also included randomly varied patient circumstances-chronic refractory symptoms and the patient requesting CAM. MEASURES: All practitioners rated the effectiveness and their willingness to recommend the therapy for a described patient. We used logistic regression to determine the independent influence of the 4 factors on respondents' effectiveness and legitimacy judgments. RESULTS: A total of 1561 practitioners responded (65%). Relative to Reiki, conventional medicine practitioners were most willing to recommend glucosamine (OR = 3.0; 95% CI [1.6 5.4]), than massage (1.9 [1.1-3.3]), acupuncture (1.3 [0.8-2.2]), and meditation (1.2 [0.7-2.0]). CAM practitioners rated acupuncture as effective more than other CAM therapies (OR = 5.8 [2.6-12.8] compared with Reiki), and were more willing to recommend acupuncture (OR = 12.3 [4.8-31.8]). When presented evidence of inefficacy, CAM practitioners were most willing to recommend acupuncture relative to other CAM therapies (OR = 15.5 [9.0-26.9]). CONCLUSIONS: Practitioners' judgments about CAM trial evidence depend on the type of treatments reported. Confirmation bias may play a role in the clinical translation of new evidence from clinical trials. PMID- 20355267 TI - Erratum: Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years' research. PMID- 20355268 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355269 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355270 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355271 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355272 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355273 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355274 TI - How insurers' bargaining power affects drug prices in Medicare Part D. PMID- 20355275 TI - Improving health insurance in developing countries. PMID- 20355276 TI - Retraction notice to "Crystal structure of Dengue virus NS3 protease in complex with a Bowman-Birk inhibitor: implications for flaviviral polyprotein processing and drug design" [J. Mol. Biol. (2000) 301, 759-767]. PMID- 20355277 TI - Is a poorly functioning health care system to blame for low life expectancy in the U.S.? PMID- 20355278 TI - Utility of PDL progenitors for in vivo tissue regeneration: a report of 3 cases. AB - OBJECTIVE: Periodontal disease is an inflammatory disorder with widespread morbidities involving both oral and systemic health. The primary goal of periodontal treatment is the regeneration of the lost or diseased periodontium. In this study, we retrospectively examined feasibility and safety of reconstructing the periodontal intrabony defects with autologous periodontal ligament progenitor (PDLP) implantation in three patients. MATERIALS AND METHODS: In this retrospective pilot study, we treated 16 teeth with at least one deep intrabony defect of probing depth (PD) > OR = 6 mm with PDLP transplantation and evaluated clinical outcome measures in terms of probing depth, gingival recession and attachment gain for a duration of 32-72 months. Furthermore, we compare PDLPs with standard PDL stem cells (PDLSCs) and confirmed that PDLPs possessed progenitor characters. RESULTS: Clinical examination indicated that transplantationof PDLPs may provide therapeutic benefit for the periodontal defects. All treated patients showed no adverse effects during the entire course of follow up. We also found that PDLPs were analogous to PDLSCs in terms of high proliferation, expression of mesenchymal surface molecules, multipotent differentiation, and in vivo tissue regain. However, PDLPs failed to express scleraxis, a marker of tendon, as seen in PDLSCs. CONCLUSIONS: This study demonstrated clinical and experimental evidences supporting a potential efficacy and safety of utilizing autologous PDL cells in the treatment of human periodontitis. PMID- 20355279 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355280 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355281 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355282 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355283 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355284 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355285 TI - No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world. PMID- 20355286 TI - Electronic coupling between cytosine bases in DNA single strands and i-motifs revealed from synchrotron radiation circular dichroism experiments. AB - In this work we have recorded synchrotron radiation circular dichroism (SRCD) spectra from 180 nm to 360 nm of cytosine strands [(dC)(n), n = 1, 2, ..., 10] in aqueous solution at different pH values to reveal electronic coupling between bases in different ionisation states. The geometry of the strands is determined by the pH value and the strand length and the local organisation of the cytosines will determine the base-to-base interaction that impacts on the CD signal. At low pH where all bases are protonated, there is no signature of electronic coupling between the bases, and the SRCD spectrum is simply n times that of the n = 1 spectrum. At higher pH where all bases are neutral, the spectra for n > 1 differ from the monomer spectrum, which implies electronic coupling between bases. The correlation between the CD signal and n is linear, and the spatial extent of the excited state wavefunction is therefore over just two stacked bases both in the UV and VUV. At intermediate pH, the low-n spectra are different from the high-n spectra, and a transition is seen to occur at n = 6-8. We ascribe this behavior to the formation of i-motif structures between four (dC)(n) strands for high n. PMID- 20355287 TI - Structural, energetic and dynamical properties of sodiated oligoglycines: relevance of a polarizable force field. AB - Oligoglycine peptides (from two to ten residues) complexed to the sodium ion were studied by quantum chemical and molecular mechanics calculations to understand their structural and energetic properties. Modeling such systems required the use of a polarizable force field and AMOEBA, as developed by Ren and Ponder [J. Comput. Chem., 2002, 23, 1497], was chosen. Some electrostatic and torsional parameters were re-optimized using a rigorous procedure and validated against both geometric and energetic ab initio data in the gas phase. Molecular dynamics simulations were performed on seven sodiated octa-glycine (G(8)) structures. Structural transitions were generally observed (with the notable exception of the a-helix), leading to new structures that were further proved by ab initio calculations to be of low energies. The main result is that for G(8)-Na(+), there is a compromise between sodium peptide interactions and multiple hydrogen bonding. The accuracy achieved with AMOEBA demonstrates the potential of this force field for the realistic modeling of gaseous peptides. PMID- 20355288 TI - Studying the stoichiometries of membrane proteins by mass spectrometry: microbial rhodopsins and a potassium ion channel. AB - In the present work we demonstrate the advantages of LILBID mass spectrometry in the mass analysis of membrane proteins with emphasis on ion-pumps and channels. Due to their hydrophobic nature, membrane proteins have to be solubilized by detergents. However, these molecules tend to complicate the analysis by mass spectrometry. In LILBID, detergent molecules are readily tolerated which allows for the study of solution phase quaternary structures of membrane proteins. This is shown for the proton-pump bacteriorhodospin and the potassium channel KcsA where in both cases the stoichiometries found by LILBID reflect the known structures from 2D or 3D crystals. With proteorhodopsin we demonstrate a preliminary detergent screening showing different structures in different detergents and the implications for the functionality of this protein. We show that Triton-X 100 prevents the formation of the pentamer of proteorhodopsin. Furthermore, the quaternary structures of proteorhodopsin cloned without the signal peptide and of the cation channel channelrhodopsin-2 were studied. The intrinsic properties of channelrhodopsin-2 allow for mass spectrometric analysis in very high salt concentrations up to 100 mM of NaCl. In summary we demonstrate that LILBID is an alternative mass spectrometric method for the analysis of membrane proteins from solution phase. PMID- 20355289 TI - Sub-microsecond photodissociation pathways of gas phase adenosine 5' monophosphate nucleotide ions. AB - The sub-microsecond dissociation pathways for the protonated and deprotonated forms of adenosine 5'-monophosphate were probed in the gas phase using a linear time of flight spectrometer. The studies show two dissociation pathways for the AMP ions indicating dominant ergodic pathways in the photodissociation of these species. The photofragmentation was determined to be a single photon process for the AMP ions. Photodetachment of the AMP anion excited at 266 nm was not observed, leaving dissociation as the prominent pathway for relaxation of the excess energy in the biomolecule. The photofragments were analysed at the electrostatic ion storage ring (ELISA) and found to be similar to collision induced fragments in the case of anions but different in the case of cations. PMID- 20355290 TI - Macromolecular crowding induces polypeptide compaction and decreases folding cooperativity. AB - A cell's interior is comprised of macromolecules that can occupy up to 40% of its available volume. Such crowded environments can influence the stability of proteins and their rates of reaction. Using discrete molecular dynamics simulations, we investigate how both the size and number of neighboring crowding reagents affect the thermodynamic and folding properties of structurally diverse proteins. We find that crowding induces higher compaction of proteins. We also find that folding becomes less cooperative with the introduction of crowders into the system. The crowders may induce alternative non-native protein conformations, thus creating barriers for protein folding in highly crowded media. PMID- 20355291 TI - DFT-MD and vibrational anharmonicities of a phosphorylated amino acid. Success and failure. AB - Following our work on the phosphorylated deprotonated serine amino acid pSerH(-) [J. Chem. Theory Comput., 2009, 5, 2388], we investigate here the room temperature infrared spectroscopy of pSerH(+) (phosphorylated protonated serine) in the gas phase in relation with IR-MPD experiment. To that end, DFT-based Car Parrinello molecular dynamics (DFTMD) are performed, giving a direct probe of vibrational anharmonicities. Agreement and disagreement with the experiment are explored in the light of DFT/functional, vibrational mode couplings and potential energy surface anharmonicities. Trends on the phosphate vibrational signatures in relation with its protonation state and environment are analysed, for the purpose of transferability into more complex phosphorylated peptide chains. PMID- 20355292 TI - Sugar-salt and sugar-salt-water complexes: structure and dynamics of glucose-KNO3 (H2O)n. AB - Molecular dynamics (MD) simulations are carried out for the complex of glucose with KNO(3) and for complexes of the type glucose-KNO(3)-(H(2)O)(n), for n < or = 11. Structure and dynamic properties of the systems are explored. The MD simulations are carried out using primarily the DL_POLY/OPLS force field, and global and local minimum energy structures of some of the systems are compared with ab initio calculations. The main findings include: (1) complexation with KNO(3) leads to an "inverse anomeric effect", with the beta-glucose complex more stable than the alpha-glucose by approximately 1.74 kcal mol(-1); (2) as temperature is increased to 600 K, the KNO(3) remains undissociated in the 1 : 1 complex, with the K(+) hooked to the equilibrium site, and the NO(3)(-) bound to it, undergoing large-amplitude bending/torsional motions; (3) for n > or = 3 water molecules added to the system, charge separation into K(+) and NO(3)(-) ions takes place; (4) for the sugar-water system with n = 11 water molecules all hydroxyl groups are hydrated with the glucose adopting a surface position, indicative of a surfactant property of the sugar; and (5) comparison of DL_POLY with MP2/TZP structure predictions indicates that the empirical force field predicts global and local minimum structures reasonably well, but errs in giving the energy rankings of the different minima. The implications of the results on the effects of salts on saccharides are discussed. PMID- 20355293 TI - Laser spectroscopic study on (dibenzo-24-crown-8-ether)-water and -methanol complexes in supersonic jets. AB - The conformation and complex formation with guest molecules have been investigated for jet-cooled dibenzo-24-crown-8-ether (DB24C8) by laser induced fluorescence (LIF), UV-UV hole-burning (UV-UV HB), and IR-UV double-resonance (IR UV DR) spectroscopy. The results are compared with the results of dibenzo-18 crown-6-ether (DB18C6) and analyzed by density functional theory (DFT) calculations at the B3LYP/6-31+G* level. Five conformers are identified for DB24C8 under jet-cooled conditions, and the structure of the major isomer is determined to be a boat form, similar to the case of DB18C6. Two molecules (water and methanol) are investigated as the guest species for the encapsulation experiment. DB24C8 hardly encapsulates a water molecule, different from the case of DB18C6 in which a water molecule is efficiently captured. However, it is likely that larger (water)(n) clusters can be captured in the DB24C8 cavity. The different feature in the complex formation between DB24C8 and DB24C8 with the water molecules are attributed to a larger cavity size of DB24C8 than that of DB18C6. For methanol, two kinds of DB18C6-(methanol)(1) isomers are identified by IR-UV DR spectroscopy; one is the "OH...pi" H-bonded isomer, characteristic of methanol with one OH group, and the other is the "OH...O" H-bonded ones. These results indicate the multiple H-bond formation to the oxygen atoms of the ether ring may play an important role in the complexes of DB24C8 or DB18C6 with water. PMID- 20355294 TI - Biodistribution analysis of cisplatin in liposomal form in animals with cisplatin resistant and cisplatin-sensitive carcinoma. AB - AIM: To analyze the relation between pharmacokinetics of cisplatin in liposomal form and antitumor efficacy toward cisplatin-resistant and cisplatin-sensitive variants of Guerin carcinoma. METHODS: Concentration of platinum was measured by atomic absorption spectrophotometry (C115M1 "Selmi", Ukraine). Elimination constant was calculated based on the dynamics of cisplatin concentration in time period between 1 h to 24 h using nonlinear regression analysis. Area under curve (AUC24) was calculated by the trapezium method. RESULTS: It was shown that for liposomal form of cisplatin (LCp) AUC24 in tumor practically didn't depend on the level of the tumor sensitivity, while in animals with the resistant variant (CpRGC), AUC24 for free cisplatin (FCp) decreased by 70% less (p < 0.001) as compared to the sensitive tumor strain (CpSGC). Significant decrease of elimination constant of LCp compared to FCp in blood serum of rats bearing either CpRGC or CpSGC tumors favors cisplatin accumulation in tumor tissues with low vascularization level. The dynamics of cisplatin concentration in CpRGC variant was characterized by 90% higher level in 24 h after administration of LCp as compared to FCp (p < 0.05). This fact may explain increased antitumor efficacy of LCp compared to FCp toward CpRGC variant. In the study of kidney function, AUC24 index for LCp was by 68.6% (p < 0.01) and 50.7% (p < 0.05) lower than AUC24 index for FCp in rats with CpRGC and CpSGC variants, respectively. No significant differences have been found in biodistribution of cisplatin in both pharmaceutical forms in liver and lung in CpRGC- or CpSGC-bearing rats. CONCLUSION: The results suggest that cisplatin in liposomal form possesses higher specificity of antitumor action than free cisplatin. PMID- 20355295 TI - My eyes water constantly. What could cause this and what can I do about it? PMID- 20355296 TI - Deceased heart beating donor and organ transplantation in Saudi Arabia. PMID- 20355297 TI - Of lives, lungs and limbs: workers at sea and onshore in the twentieth century. PMID- 20355298 TI - James Lind and scurvy: a revaluation. PMID- 20355299 TI - [The state, the church, and contentious married couples: a new view of marriage in the first half of the 19th century]. PMID- 20355300 TI - [Inside marriage - outside marriage: national and scientific tools to control prostitution and sexuality in the 19th century]. PMID- 20355301 TI - [The girl from the baker's shop and the bugler: outside marriage in Godvad in the second half of the 19th century]. PMID- 20355302 TI - [Surveillance and regulation of female prostitution, 1920-60]. PMID- 20355303 TI - [Adultery in 18th- and 19th-century Danish rural society]. PMID- 20355304 TI - Polygeline for adult dengue haemorrhagic fever and spectrum of unusual manifestations. PMID- 20355305 TI - Epigastric pain due to duodenal ascaris infection. PMID- 20355306 TI - Pepsinogen I and II and the ratio pepsinogen I/II in detecting atrophic gastritis. PMID- 20355307 TI - Management of heart failure in elderly patients. PMID- 20355308 TI - Electronic health records objectives. PMID- 20355310 TI - Looking for answers? Ask the patients. PMID- 20355309 TI - The Provider Enrollment, Chain and Ownership System (PECOS). PMID- 20355311 TI - [Excerpts to contribute to the Johan-case: without comment]. PMID- 20355312 TI - [The importance of social pediatry knowledge in pediatric primary care]. PMID- 20355313 TI - Bioreduction of some common carbonylic compounds mediated by yeasts. AB - Bioreduction of several prochiral carbonylic compounds such as acetophenone (1), ethyl acetoacetate (2) and ethyl phenylpropionate (3) to the corresponding optically active sec-alcohols 1a-3a was performed using wild-type strains of Pichia pastoris UBB 1500, Rhodotorula sp., and Saccharomyces cerevisiae. The reductions showed moderate to excellent conversion and high enantiomeric excess, in an extremely mild and environmentally benign manner in aqueous medium, using glucose as cofactor regeneration system. The obtained alcohols follow Prelog's rule, but in the reduction of 1 with P. pastoris UBB 1500 the anti-Prelog enantiopreference was observed. PMID- 20355314 TI - Mutagenicity of bisbenzimidazole derivatives. AB - The mutagenicities of 2,2'-(di-3-hydroxyphenyl)-1H,1H'-[5,5']-bisbenzimidazole, 2,2'-(di-4-hydroxyphenyl)-1H,1H'-[5,5']-bisbenzimidazole, 2,2'-(di-3 methoxyphenyl)-1H,1H'-[5,5']-bisbenzimidazole, 2,2'-bis-(4-nitrophenyl)-1H,1H' [5,5']-bisbenzimidazole, 2,2'-bis-(3-nitrophenyl)-1H,1H'-[5,5']-bisbenzimidazole, 2,2'-bis-(4-methylphenyl)-1H,1H'-[5,5']-bisbenzimidazole, 2,2'-(di-4 methoxyphenyl)-1H,1H'-[5,5']-bisbenzimidazole, and 2,2'-bis-(3-methylphenyl) 1H,1H'-[5,5']-bisbenzimidazole were studied in vitro using two strains of Salmonella typhimurium with frameshift mutation (TA98) and base-pair substitution mutation (TA100) as the plate incorporation assay in the absence of metabolic activation. These compounds are currently used to treat cancer. 4-Nitrophenyl and 3-nitrophenyl compounds were found to be mutagenic on both strains of Salmonella. A clear mutagenic response was seen in nitro-bound derivatives. The mutagenic response in Salmonella test strains (TA98, TA100) and structures of molecules suggest that nitro-bound molecules could be mutagenic. PMID- 20355315 TI - Synthesis and antimicrobial activity of new substituted 1,2,4-triazoles and their acyclic C-nucleoside analogues. AB - A number of new substituted 1,2,4-triazole {[(1,2,4-triazolyl)ethyl]tetrazolyl} derivatives, their sugar hydrazones, and their acyclic C-nucleoside analogues were synthesized and tested for their antimicrobial activity against Bacillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes). The synthesized compounds displayed different degrees of antimicrobial activities or inhibitory actions. PMID- 20355316 TI - Synthesis and antimicrobial activity of new substituted fused 1,2,4-triazole derivatives. AB - A number of new substituted 1,2,4-triazole, 1,2,4-triazolo[3,4-b]1,3,4 thiadiazole and 1,2,4-triazolo[3,4-b]1,3,4-thiadiazine derivatives were synthesized and tested for their antimicrobial activity against Bacillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes). The synthesized compounds displayed different degrees of antimicrobial activities or inhibitory actions. PMID- 20355317 TI - New analogues of acyclovir--synthesis and biological activity. AB - New acyclovir esters with peptidomimetics were synthesized and evaluated in vitro for their antiviral activity against the replication of Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The influence of peptidomimetics containing oxazole and thiazolyl-thiazole moieties on the antiviral activity is also reported. The esters were synthesized using the coupling reagents N-ethyl-N'-(3 dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N,N-dimethyl-4 aminopyridine (DMAP) as a catalyst. PMID- 20355318 TI - Antibacterial activities of Ramalin, usnic acid and its three derivatives isolated from the Antarctic lichen Ramalina terebrata. AB - The development of new antibacterial compounds is an urgent issue to meet the evolution of resistivity of pathogenic bacteria against the available drugs. The objective of this study was to investigate the antibacterial compounds from the Antarctic lichen species Ramalina terebrata. A total of five compounds, usnic acid, usimine A, usimine B, usimine C, and ramalin, were isolated by bioactivity guided-fractionation of the methanol extract of R. terebrata after several chromatographic procedures. The qualitative antibacterial activities of the crude extract and isolated compounds were determined by the disk diffusion method while the minimum inhibitory concentration (MIC) determination assay gave the quantitative strength of the test samples. All the test samples showed antibacterial activity against Bacillus subtilis. The crude extract and usnic acid showed antibacterial activity against Staphylococcus aureus. The MIC values of the isolated compounds against B. subtilis were in the range of 1 to 26 microg/mL. These observed experimental data showed the strong antibacterial potential of these compounds against B. subtilis. PMID- 20355319 TI - Anticancer activity of diterpenoids from Amoora ouangliensis and Amoora stellato squamosa. AB - A new ent-halimane-type diterpene, named 5(10),14-ent-halimadien-3beta,13S-diol (1), was isolated from the bark of Amoora ouangliensis and its chemical structure determined on the basis of spectroscopic analysis. Additionally, ten other diterpenoids were obtained from A. ouangliensis and A. stellato-squamosa. The bioactive experiments of all compounds against AGZY 83-a (human lung cancer cells) and SMMC-7721 (human liver cancer cells) cells were documented. PMID- 20355321 TI - Inhibitory effect of hydroxyindoles and their analogues on human melanoma tyrosinase. AB - A recent study showed that N-acylserotonin derivatives have strong inhibitory activity against tyrosinase. To clarify the role of the 5-hydroxy group in the indole ring, 2-, 4-, 5-, 6-, and 7-hydroxyindole and 11 related compounds such as 5-hydroxyindan and 6-hydroxyquinoline were tested for their inhibition of catecholase activity of tyrosinase from human HMV-II melanoma cells. 6 Hydroxyindole (5) and 7-hydroxyindole (6) were potent inhibitors, while 5 hydroxyindole (4) was a weaker inhibitor than the above-mentioned compounds (IC50 = 20, 79, 366, and 342 microM for 5, 6, 4, and kojic acid, respectively). 2 Hydroxycarbazole was also active (IC50 = 190 microM), 5-hydroxyindan, 4 aminophenol, and harmalol were slightly active, and other compounds were inactive as an inhibitor. A similar pattern of inhibition was found with these compounds against mouse B16 melanoma tyrosinase, but with some differences from that for HMV-II tyrosinase. Kinetic analysis with HMV-II tyrosinase showed that the inhibition by hydroxyindoles 4, 5, and 6 was competitive with respect to the substrate L-DOPA. Melanin formation in HMV-II cells was suppressed by 14% with 10 microM 5 without cytotoxicity, but 30 or 100 microM 5 decreased the cell viability. The present results suggest that 6-hydroxyindole is a potential and useful pharmacophore of antimelanogenic agents and that the position of a phenolic hydroxy group in a specific heterocyclic ring such as in indole is possibly optimized to yield more active inhibitors for tyrosinase. PMID- 20355320 TI - In vitro antitumour activity of orsellinates. AB - Lichen phenolic compounds exhibit antioxidant, antimicrobial, antiproliferative, and cytotoxic activities. The purpose of this study was to evaluate the anticancer activity of lecanoric acid, a secondary metabolite of the lichen Parmotrema tinctorum, and its derivatives, orsellinates, obtained by structural modification. A cytotoxicity assay was carried out in vitro with sulforhodamine B (SRB) using HEp-2 larynx carcinoma, MCF7 breast carcinoma, 786-0 kidney carcinoma, and B16-F10 murine melanoma cell lines, in addition to a normal (Vero) cell line in order to calculate the selectivity index of the compounds. n-Butyl orsellinate was the most active compound, with IC50 values (the concentration that inhibits 50% of growth) ranging from 7.2 to 14.0 microg/mL, against all the cell lines tested. The compound was more active (IC50 = 11.4 microg/mL) against B16-F10 cells than was cisplatin (12.5 microg/mL). Conversely, lecanoric acid and methyl orsellinate were less active against all cell lines, having an IC50 value higher than 50 microg/mL. Ethyl orsellinate was more active against HEp-2 than against MCF7, 786-0, or B16-F10 cells. The same pattern was observed for n-propyl and n-butyl orsellinates. n-Pentyl orsellinate was less active than n-propyl or n butyl orsellinates against HEp-2 cells. The orsellinate activity increased with chain elongation (from methyl to n-butyl), a likely consequence of an increase in lipophilicity. The results revealed that the structural modification of lecanoric acid increases the cytotoxic activity of the derivatives tested. PMID- 20355322 TI - Microbial transformation of selected flavanones as a method of increasing the antioxidant properties. AB - Antioxidant properties of substrates [flavanone (1), 6-hydroxy- (2), 7-hydroxy- (3), 5,7,4'-trihydroxy- (5), and 7-methoxyflavanone (4)] and products of their microbial transformations, comprising hydroxylation, O-methylation, stereospecific reduction, dehydrogenation, and C-ring cleavage of the benzo-gamma pyrone system, were determined. Measurements of the antiradical activity (expressed as IC50 value) of both the substrates and the products led to the determination of the impact of type and location of substituents in the tested flavonoids on changes in their antioxidant activities. PMID- 20355323 TI - Concomitant production, partial purification and characterization of a serine protease and a proteolysis-resistant metallolipase from Bacillus pumilus SG2. AB - Our objective was to investigate the concomitant production of protease and lipase by a bacterial strain. A promising bacterial strain was isolated from a food-processing industrial effluent, which can produce both protease and lipase. The isolate was characterized by sequencing the 16S rRNA gene. The PCR amplified gene was subjected to analysis by BLAST to ascertain the genetic relatedness of the isolate, Bacillus pumilus SG2. The enzymes were produced and subjected to purification by ammonium sulfate precipitation and dialysis followed by gel filtration chromatography; twelve-fold purity was obtained. The lipase produced was found to be proteolysis-resistant. The partially purified enzymes were characterized for their optimum pH value, temperature, response to inhibitors, surfactants and oxidants. The relative molecular weights of protease and lipase were determined as 28 kDa and 40 kDa, respectively, by zymogram studies. PMID- 20355325 TI - Difference of physiological characters in dark green islands and yellow leaf tissue of Cucumber mosaic virus (CMV)-infected Nicotiana tabacum leaves. AB - Dark green islands (DGIs) are a common symptom of plants systemically infected with the mosaic virus. DGIs are clusters of green leaf cells that are free of virus but surrounded by yellow leaf tissue that is full of virus particles. In Cucumber mosaic virus (CMV)-infected Nicotiana tabacum leaves, the respiration and photosynthesis capabilities of DGIs and yellow leaf tissues were measured. The results showed that the cyanide-resistant respiration was enhanced in yellow leaf tissue and the photosynthesis was declined, while in DGIs they were less affected. The activities of the oxygen-scavenging enzymes catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in infected leaves were significantly higher than those in the healthy leaves, and the enzyme activities in DGIs were always lower than in the yellow leaf tissues. Reactive oxygen species (ROS) staining showed that the hydrogen peroxide content in yellow leaf tissues was apparently higher than that in DGIs, while the superoxide content was on the contrary. Formation of DGIs may be a strategy of the host plants resistance to the CMV infection. PMID- 20355324 TI - Cell phone radiations affect early growth of Vigna radiata (mung bean) through biochemical alterations. AB - The indiscriminate use of wireless technologies, particularly of cell phones, has increased the health risks among living organisms including plants. We investigated the impact of cell phone electromagentic field (EMF) radiations (power density, 8.55 microW cm(-2)) on germination, early growth, proteins and carbohydrate contents, and activities of some enzymes in Vigna radiata. Cell phone EMF radiations significantly reduced the seedling length and dry weight of V radiata after exposure for 0.5, 1, 2, and 4 h. Furthermore, the contents of proteins and carbohydrates were reduced in EMF-exposed plants. However, the activities of proteases, alpha-amylases, beta-amylases, polyphenol oxidases, and peroxidases were enhanced in EMF-exposed radicles indicating their role in providing protection against EMF-induced stress. The study concludes that cell phone EMFs impair early growth of V radiata seedlings by inducing biochemical changes. PMID- 20355326 TI - Light stress is not effective to enhanced crassulacean acid metabolism. AB - Clusia minor L., a C3-CAM intermediate, and Clusia multiflora H. B. K., a C3 obligate, present two physiotypes of a similar morphotype occurring sympatrically in the field. Both species, exposed 2 days to high light, show similar responses to this kind of stress: (i) the level of xanthophyll pigments in tested plants during the daycourse adapts to stress, (ii) the levels of antheraxanthin and zeaxanthin clearly increase during the afternoon showing increased de epoxidation, (iii) the changes in the xanthophyll cycle are similar. Exposure to high light increases the malate levels in C. minor during the afternoon while decreases the day/night changes of the malate levels, and hence the Crassulacean Acid Metabolism (CAM) expression. It can be concluded that strong light applied as a single stress factor to well-watered plants is not effective in strengthing the CAM metabolism in a C3-CAM intermediate plant but rather suppresses the CAM activity despite exposure to high light energy. It is suggested that, when water supply is not limiting and other stresses do not prevail, C3 allows to use up the citrate pool, especially in the afternoon and enables a superior daily photon utilization. PMID- 20355328 TI - Cadmium- and flood-induced anoxia stress in pea roots measured by electrical impedance. AB - Electrical impedance measurement--complex resistance in the presence of alternating current--is a useful tool for the investigation of structural characteristics of solid materials but also for plant tissues. This measurement is easily done: only two electrodes are inserted into the plant tissue, so it can be considered as a non-invasive technique and it may be a successful method for detecting structural changes in plants caused by environmental stresses. The effects of flood and cadmium stress were investigated by electrical impedance measurement, because both of them cause structural changes in plant tissues. Apoplasmic resistance (Ra), symplasmic resistance (Rs), and membrane capacitance (Cm) of pea roots were calculated. In the first five days of flood treatment, the Rs and Cm values of roots decreased drastically. In case of cadmium treatment, the Rs and Cm values of roots showed an increasing tendency supposedly as a consequence of the enhanced membrane rigidity, the thickened cell walls and decreased growth phenomena caused by the heavy metal. There also was a remarkable difference in cadmium accumulation patterns and in the changes of the calculated parameters amongst anoxic and aerated seedlings. This initial work revealed that the development of stress caused by two environental stress agents, cadmium and flood, can be followed by electrical impedance measurement. PMID- 20355327 TI - Effects of cadmium stress on alternative oxidase and photosystem II in three wheat cultivars. AB - The effects of Cd stress (200 micromol/L, 8 days) on respiration and photosynthesis of three wheat cultivars were investigated: Chuanyu 12 (CY12), Chuanmai 42 (CM42), and Chuanmai 47 (CM47). Fifteen-day-old seedlings were exposed to 200 micromol/L CdCl2 for 4 days and 8 days, respectively. The results indicated that Cd was accumulated largely in roots, but little in leaves of all three cultivars. CY12 accumulated the highest level of Cd in roots and showed the weakest resistance. On the contrary, the other two cultivars, CM42 and CM47, adapted better to Cd stress, and their thiobarbituric acid-reactive substances (TBARS) contents were lower than in CY12, but the chlorophyll contents and water contents were higher than in CY12. Additionally, Cd stress prompted the alternative oxidase (AOX) activity and upregulated the cyanide-resistant respiration in CM42 and CM47 after 8 days; no such induction was observed for CY12. The CO2 assimilation rate, leaf stomatal conductance and chlorophyll fluorescence were inhibited by Cd stress in all cultivars, but more severe in the CY12 cultivar. Western blots indicated that the content of the photosystem II proteins LHCII and D1 decreased in CY12, but did not change in CM42 and CM47. While the content of the mitochondrial AOX protein increased markedly in CM42 and CM47, it did not in CY12. These results suggested that AOX and LHCII could be regarded as indicators of plant's resistance to heavy metals. PMID- 20355329 TI - Cloning and expression analysis of carboxyltransferase of acetyl-coA carboxylase from Jatropha curcas. AB - A full-length cDNA of the carboxyltransferase (accA) gene of acetyl-coenzym A (acetyl-CoA) carboxylase from Jatropha curcas was cloned and sequenced. The gene with an open reading frame (ORF) of 1149 bp encodes a polypeptide of 383 amino acids, with a molecular mass of 41.9 kDa. Utilizing fluorogenic real-time polymerase chain reaction (RT-PCR), the expression levels of the accA gene in leaves and fruits at early, middle and late stages under pH 7.0/8.0 and light/darkness stress were investigated. The expression levels of the accA gene in leaves at early, middle and late stages increased significantly under pH 8.0 stress compared to pH 7.0. Similarly, the expression levels in fruits showed a significant increase under darkness condition compared to the control. Under light stress, the expression levels in the fruits at early, middle and late stages showed the largest fluctuations compared to those of the control. These findings suggested that the expression levels of the accA gene are closely related to the growth conditions and developmental stages in the leaves and fruits of Jatropha curcas. PMID- 20355330 TI - cDNA cloning, heterogeneous expression and biochemical characterization of a novel trypsin-like protease from Nilaparvata lugens. AB - A reverse transcription-polymerase chain reaction (RT-PCR) strategy was used to clone diverse trypsin-like protease gene transcripts from midguts of the brown planthopper Nilaparvata lugens Stal (Homoptera: Delphacidae). Six individual trypsin-like protease transcripts were identified. On the basis of one nucleotide sequence of the six clones, a full-length cDNA sequence (1902 bp) was obtained by rapid amplification of cDNA ends (RACE). The cDNA contained an 1128-bp open reading frame encoding a putative protein of 375 amino acids with typical features of the trypsin-like protease. Heterogeneous expression of the coding sequence for the mature peptide in Escherichia coli cells showed that the expressed protease with a molecular weight of 27.0 is active, for its BApNAse activity assayed by using BApNA (N-benzoyl-D,L-arginine-p-nitroanilide) as substrate. The protease had its maximum activity at pH 8.0 and 35 degrees C. A much better stability was observed at pH values above 4.0 and temperatures below 40 degrees C. The enzyme was strongly inhibited by serine protease inhibitor. The trypsin-like protease is therefore likely one of the major digestive proteases responsible for protein hydrolysis in N. lugens gut, and multiple gene families encoding digestive proteases may help in adaptation of this sap-sucker to different rice varieties. PMID- 20355331 TI - Expression and localization of Bombyx mori V-ATPase 16 kDa subunit c. AB - V-ATPase plays a central role in lepidopteran midgut ion transport physiology, and lepidopteran midgut turned out to be a model tissue for the study of V ATPase. In the present study, the 5'-RACE method is used to obtain the 5'-UTR of V-ATPase c subunit gene from Bombyx mori. Sequence analysis of the promoter region and 3'-UTR of V-ATPase c subunit gene revealed that the transcription of the V-ATPase c subunit gene may be regulated by multi-ways. RT-PCR analysis showed that B. mori V-ATPase c subunit mRNA expresses in the whole developmental stages of B. mori. We also constructed a transient vector to determine the subcellular localization of the B. mori V-ATPase c subunit, and the result demonstrated that it is located in the membrane and some specific regions of BmN cells. Real-time PCR analysis further indicated that the c subunit mRNA expression was upregulated significantly at 24 and 72 h in the midguts of resistant B. mori larvae after being inoculated with B. mori nucleopolyhedrovirus, suggesting that it may be related to the immune response against virus infection. PMID- 20355332 TI - Optimization of solid-phase microextraction sampling for analysis of volatile compounds emitted from oestrous urine of mares. AB - The solid-phase microextraction (SPME) technique was applied and optimized for collection of volatile compounds emitted from oestrous urine of mares Equs cabalus L. (Perissodactyla, Equidae) for GC-MS analyses. Variables such as type of SPME fibre, collection time of volatiles, and addition of salt were optimized to improve the sampling efficiency in two aspects: extent and selectivity of absorption/adsorption of urine volatiles onto SPME fibres. The data revealed that the number of volatiles and the total amount represented as quantitative peak areas of the compounds trapped on fibres coated either with polydimethylsiloxane divinylbenzene or with divinylbenzene-carboxen-polydimethylsiloxane were significantly higher compared to those coated with polydimethylsiloxane, polyacrylate, and carbowax-divinylbenzene. The polydimethylsiloxane divinylbenzene-type of fibre coating was chosen for optimization of sampling time and effect of salt addition. Sampling periods lasted for 15, 30, 60, 120, and 240 min. The optimal collection time of volatiles from urine maintained at about 36 degrees C was 60 min, as the number of compounds detected with amounts sufficient for quantification did not differ significantly from those trapped during longer collection periods. No significant increase in total amount of volatiles trapped was registered after 120 min of sampling. Addition of 0.3 g NaCl to the 2-ml of samples shortened the collection period from 60 to 15 min during which almost all compounds were trapped. Addition of salt has a significant effect at all sampling periods taking into consideration the total amounts of volatiles trapped. The total intensities increased about 8, 5, 3, 3, and 2 times at collection periods of 15, 30, 60, 120, and 240 min, respectively, when compare with the ones obtained from the urine samples with no salt addition. In oestrous mare's urine, 139 +/- 4 (average number +/- standard deviation) volatile compounds suitable for quantitative analyses were detected compared to 45 compounds collected by the gas tight syringe method. PMID- 20355333 TI - Degradation of native feathers by a novel keratinase-producing, thermophilic isolate, Brevibacillus thermoruber T1E. AB - Strain T1E, isolated and identified as Brevibacillus thermoruber, and evolutionally distant from the known keratinolytic isolates, proved to have feather-degrading ability. During the 7-day fermentation period, T1E consumed 10 g/l native goose feathers as the sole source of carbon and energy at 50 degrees C under aerobic conditions. The isolate secreted a thermostable, keratinolytic protease, which exhibited activity optimally at pH 6.5, whilst it was inhibited at alkaline pH. The keratin cleavage and catabolism resulted in the accumulation of free aspartic acid and soluble peptides with maximum values of 31.6 and 720 mg/l, respectively. The majority of the fermentation end-products were found to be small oligopeptides with an average molecular mass of 2275 Da. PMID- 20355334 TI - Effect of yeast superoxide dismutase treatment on some mediators of inflammation during adjuvant-induced arthritis in mice. AB - * Author for correspondence and reprint requests Z. Naturforsch. 65c, 141-147 (2010); received June 17/July 21, 2009 The superoxide radical (O2-), hydrogen peroxide (H2O2) and nitric oxide (NO) are pleiotropic inflammatory mediators which play an important role in inflammatory joint diseases. They are overproduced during rheumatoid arthritis and its experimental model - adjuvant induced arthritis in rodents--and may be detected both systemically and intra articularly. Their secretion is up-regulated by proinflammatory cytokines such as IFN-gamma, IL-12, IL-6 and TNF-alpha, and they are responsible for the destruction of joint tissue. In this work, the effect of superoxide dismutase (SOD) from a thermotolerant yeast strain, Kluyveromyces marxianus, on the production of proinflammatory cytokines, reactive oxygen and nitrogen species was studied. Mice received three intraperitoneal injections of yeast SOD at a dose of 10 mg/ kg body weight (30,000 U/kg) on consecutive days starting on the day after arthritic induction. On days 3, 8 and 14 post induction peritoneal macrophages were isolated and both spontaneous and stimulated production of reactive oxygen and nitrogen metabolites were measured. Early in arthritic development yeast SOD treatment did not influence the O2- production, but on day 14 both spontaneous and PMA-induced secretion were dramatically reduced. Spontaneous H2O2 release was inhibited on day 14, while PMA-stimulated production was decreased from the beginning of the arthritic development. Yeast SOD treatment effectively suppressed the spontaneous and recombinant mouse IFN-gamma + LPS induced release of NO as well. Serum levels of proinflammatory cytokines, IL-12, IFN-gamma, IL-6 and TNF-alpha, were also significantly reduced. The obtained results show some of the mechanisms of action of SOD in reducing the severity of arthritic inflammation. Besides direct inhibition of joint tissue destruction exogenous SOD substantially limits the existing positive feedback between secretion of reactive oxygen species and inflammatory cytokine production. PMID- 20355335 TI - Lack of effect of RuvB-like proteins on DNA damage signaling activation. AB - Ataxia telangiectasia mutated (ATM) kinase is a central player in cellular response to DNA damage. Phosphorylation of the histone H2AX by ATM is required for the accumulation of repair proteins at the sites of double-strand breaks. Recently, it was reported that the histone acetyltransferase Tat interactive protein-60 (IPP60) is required to acetylate ATM prior to its activation. The RuvB like proteins TIP48 and TIP49 are known to be necessary for the assembly and functional activity of the TIP60 acetyltransferase complex. In the present communication, we investigated the requirements of IIP48 and IIP49 for ATM activation by monitoring the cell cycle distribution and H2AX phosphorylation after irradiation of IIP48- and IIP49-depleted cells. We found that neither the cell cycle norgammay-H2AX were affected in IIP48- and IIP49-silenced cells, suggesting that the IIP60 chromatin modification complex is not engaged in DNA damage signaling upstream of ATM. PMID- 20355336 TI - Production of recombinant human granulocyte macrophage colony-stimulating factor from silkworm Bombyx mori Bm5 cells. AB - Using silkworm Bombyx mori Bm5 cells, we established a stable cell line expressing the human granulocyte macrophage colony-stimulating factor (hGM-CSF), which gets its name from the Bm5-hGM-CSF cell in which the glycoprotein of the hGM-CSF is secreted in the cell culture supernatant (CCS). It was demonstrated that secreted hGM-CSF had in vivo biological activity and the white blood cell (WBC) value increased two times that of the control. We expect to produce useful human recombinant glycoproteins from silkworm cultured cells for a low price and a large quantity. PMID- 20355337 TI - Make the strategy a reality. PMID- 20355338 TI - Dementia tsar appointed to give direction to strategy. PMID- 20355339 TI - Is alcohol misuse only a problem in the younger generation? PMID- 20355340 TI - Making a difference as a nurse consultant. AB - The nurse consultant role has existed for a decade. The five components of the role--professional leadership, service development, research, education and training, and expert practice--are discussed in relation to Aileen Fraser's work with older people in Bristol. Ms Fraser explains how she has identified gaps in services and developed new policies to improve practice on safeguarding vulnerable adults. She also discusses how she has been influenced by good practice she witnessed on a study tour in the United States. PMID- 20355341 TI - A dementia education scheme. AB - The Cornwall dementia and communication difficulties education scheme is a simple strategy to enable provision of more effective and appropriate care to patients with memory and communication difficulties throughout healthcare settings in Cornwall. An acute hospital audit found that the scheme improved awareness, documentation and care of this patient group. The scheme has become the basis of Cornwall's dementia strategy. PMID- 20355342 TI - How to make care champions. AB - This article provides an overview of how second-year, adult branch nursing students at De Montfort University, Leicester, were trained as older people's champions to improve the care provided to this patient group. PMID- 20355343 TI - Caring for people with end-stage dementia. AB - This article considers the role of palliative care in the management of patients with dementia. It aims to broaden the knowledge of nurses providing general care as well as specialist palliative and end of life care to patients with dementia in all settings. The article helps nurses to identify the characteristics of end stage dementia and meet the associated challenges that this diagnosis poses. Nurses should then be in a better position to recognise and support patients and their families and ensure that palliative care is included in care planning for this group of patients. PMID- 20355344 TI - Face to face: Rona Agnew. PMID- 20355345 TI - A church-based intervention to promote informed decision making for prostate cancer screening among African American men. AB - OBJECTIVES: This feasibility study developed and pilot tested an intervention to: (1) increase knowledge about prostate cancer screening; and (2) promote self efficacy to participate in the informed decision-making process. SETTING: African American men are a priority audience for prostate cancer screening interventions to promote informed decision making, and faith-based settings have been shown to be an effective venue to reach this population. Therefore we used predominantly African American churches to develop and test our intervention. PARTICIPANTS: Participants (N = 73) were recruited, and the intervention was administered by an African American health educator. INTERVENTION: We developed and pretested a prostate cancer screening informed decision-making intervention based on the Ottawa Decision Support Framework and the health belief model. The intervention included a tool called the "road map," which depicts the potential consequences of a decision to undergo or forgo screening. A quasiexperimental design was used to test the intervention. MAIN OUTCOME MEASURES: The main outcome measures were change in knowledge and self-efficacy post intervention. RESULTS: Prostate cancer knowledge (p < .0001) and self-efficacy (p = .025) significantly increased. CONCLUSIONS: A church-based intervention delivered by an African American health educator is a promising strategy for promoting informed decision making among African American men. PMID- 20355346 TI - Pros and cons of prostate cancer screening: associations with screening knowledge and attitudes among urban African American men. AB - Discussion of the pros and cons of prostate cancer screening tests, rather than routine screening, is recommended to support informed screening decisions, particularly among African American men. This study explored physician explanation of pros and cons of the prostate-specific antigen (PSA) test and digital rectal exam (DRE) and its association with knowledge and screening attitudes. Two hundred-one African American men were asked if a physician had ever provided a comprehensive explanation of pros and cons of the PSA test and DRE. All men completed a 10-item prostate cancer knowledge scale and a subset completed a 26-item attitudes measure. Only 13% of the sample reported receiving a comprehensive explanation. Also, prostate cancer knowledge in the sample was low (mean = 43% correct). Multivariate analyses revealed that total prostate cancer knowledge was associated with men receiving a comprehensive explanation (p = .05), as well as past prostate cancer screening (p = .02) and younger age (p = .009). Although comprehensive explanation of prostate cancer screening was related to total prostate cancer knowledge, it was unrelated to a subset of items that may be central to fully informed screening decisions. Furthermore, comprehensive explanation of prostate cancer screening (p = .02), along with DRE recommendation (p = .009) and older age (p = .02), were related to fewer negative screening attitudes. Findings suggest that continued focus on patient education and physician communication is warranted. PMID- 20355348 TI - Less-than-standard treatment in rectal cancer patients: which patients are at risk? AB - OBJECTIVE: Guidelines recommend that patients with nonmetastatic rectal cancer receive surgery and adjuvant chemotherapy and/or radiation therapy (XRT) after surgery (especially if stage II and III). Studies reported that 90% of stage II and III patients received surgery, and 70% received adjuvant treatment. In states where socioeconomics and limited medical resources may hinder treatment, cancer care is understudied. The objective is to describe initiation and completion of rectal cancer treatment in Alabama. METHODS: Medicare claims were obtained for 675 stage I to III rectal cancer patients diagnosed in 1999-2003, enrolled in fee for-service Medicare, and with at least 9 months of followup. Logistic regressions were used to identify significant differences by sex, age, and race in the likelihood of initiating treatment and receiving an incomplete course of chemotherapy or XRT (< or = 120 days of chemotherapy and < or = 28 days of XRT). RESULTS: Overall, 90% received surgery, of which 43% received some adjuvant treatment. Among stage II to III patients, 58.8% received adjuvant treatment. Except for patients aged 75 years and greater being less likely to start chemotherapy, there were no significant differences in initiation by age, sex, and race. Depending on concurrent administration of chemotherapy and XRT, 29% to 35% received incomplete chemotherapy, and 16% to 23% incomplete XRT. Women were more likely to have incomplete chemotherapy than men. CONCLUSIONS: Adjuvant treatment was less than reported in previous studies. Treatment initiation and completion did not differ across demographic factors. Future studies should explore reasons why older rectal cancer patients in Alabama are less likely to receive recommended treatment. PMID- 20355349 TI - Relationship among age, race, medical funding, and cervical cancer survival. AB - OBJECTIVE: To examine the impact of age, race, and medical funding on cervical cancer survival. MATERIALS AND METHODS: Study design was a retrospective chart review of cervical cancer patients. Charts were abstracted for demographic characteristics, Pap smear history, clinical presentation, treatment, and survival. Descriptive studies, Spearman correlation, and Cox's proportional hazards regression model were performed. RESULTS: One hundred-twenty-five cervical cancer patients were included. Mean age at diagnosis was 46.1 +/- 13.2 years, and median survival time from cervical cancer was 31 months; 11.2% of the study population was aged greater than 65 years; 63.4% were African American; and 44.6% had no medical funding. Diagnosis at age of at least 65 years was significantly correlated with suboptimal cervical cancer screening pattern (r = 0.36, p = .0003). Women aged at least 65 years old had a 3.39 time increased hazard of death compared to younger patients (p = .02; OR, 3.39; 95% CI, 1.20 9.56) after adjusting for advanced stage of disease and treatment modality. There was no significant association between medical funding or race on cervical cancer screening pattern, stage at diagnosis, or survival. CONCLUSION: Age at diagnosis (> or = 65 years), but not medical funding or race, was correlated with suboptimal cervical cancer screening pattern and poor survival. PMID- 20355347 TI - Race/ethnicity-based concerns over understanding cancer diagnosis and treatment plan. AB - BACKGROUND: Race/ethnicity and culture influence illness perceptions, health beliefs and behaviors, and communication with health care providers. However, information about the impact of race/ethnicity on the understanding of cancer diagnosis and treatment plan is limited. METHODS: Nine hundred seventy-three cancer patients completed an information needs-assessment questionnaire prior to starting treatment at 20 geographically distinct clinical cancer sites within the University of Rochester Community Clinical Oncology Program network. Chi2 Test was used to examine the association between race/ethnicity and education, occupation, and perception and use of available information. T test and analysis of covariance were used to examine race/ethnicity-based differences in concerns over understanding cancer diagnosis/treatment plan and the effect of race/ethnicity controlling for demographics. RESULTS: There were 904 non-Hispanic white and 69 nonwhite (blacks, Latinos, and others) patients in the sample. Whites and nonwhites were comparable in educational attainment and occupation. However, there was a statistically significant race/ethnicity-based difference in concerns over understanding the diagnosis and treatment plan for cancer, even after controlling for sex (male, female), age, education, and occupation (p < .001). More nonwhite patients indicated that additional information would have been helpful in dealing with these concerns (p <.001). CONCLUSIONS: Nonwhite cancer patients reported more concerns about understanding their diagnosis and treatment plan and were more likely to indicate that additional information would have been helpful. The findings emphasize the need for oncology professionals to confirm patients' understanding and ensure patients' information needs have been met, particularly when working with racial/ethnic minorities. PMID- 20355350 TI - Barriers related to mammography use for breast cancer screening among minority women. AB - PURPOSE: The purpose of this review was to better understand possible social, economic, cultural, behavioral, and systems barriers to breast cancer screening among minority women. METHODS: Relevant manuscripts were identified through a MEDLINE/PubMed search for English-language literature from October 1971 through April 2009. The abstracts from a total of 515 manuscripts were reviewed. Only studies conducted among minority women in the United States and examining barriers related to screening mammography were considered. Of 64 relevant articles, 13 cross-sectional and 4 prospective studies met inclusion criteria. Study design; patient characteristics; outcomes regarding knowledge, attitudes and beliefs; social norms; accessibility; and cultural competence regarding breast cancer screening were abstracted. Studies were rated using a methodological quality score (MQS). RESULTS: Pain and embarrassment associated with screening mammography, low income and lack of health insurance, poor knowledge about breast cancer screening, lack of physician recommendation, lack of trust in hospitals and doctors, language barriers, and lack of transportation were the most frequently identified barriers. The average MQS of the studies selected was 10.9 (SD = 3.25, range, 4-20). CONCLUSIONS: Multiple barriers limit screening mammography among minority women. Recognizing predictors of screening among minority women and addressing culturally specific barriers may improve utilization of screening mammography among these women. PMID- 20355351 TI - Self-reported willingness to have cancer screening and the effects of sociodemographic factors. AB - BACKGROUND: The relative effects of race/ethnicity and other sociodemographic factors, compared to those of attitudes and beliefs on willingness to have cancer screening, are not well understood. METHODS: We conducted telephone interviews with 1148 adults (22% Hispanic, 31% African American, and 46% white) [corrected] from 3 cities in mainland United States and Puerto Rico. Respondents reported their sociodemographic characteristics, attitudes about barriers and facilitators of cancer screening, and willingness to have cancer screening under 4 scenarios: when done in the community vs one's doctor's office, and whether or not one had symptoms. RESULTS: Racial/ethnic minority status, age, and lower income were frequently associated with increased willingness to have cancer screening, even after including attitudes and beliefs about screening. Having screening nearby was important for community screening, and anticipation of embarrassment from screening for when there were no cancer symptoms. Associations varied across 4 screening scenarios, with the fewest predictors for screening by one's doctor when there were symptoms. CONCLUSIONS: Sociodemographic characteristics not only were related to willingness to have cancer screenings in almost all cases, but were generally much stronger factors than attitudinal barriers and facilitators. Cancer screening campaigns should affect attitudinal change where possible, but should also recognize that targeting screening to specific population groups may be necessary. PMID- 20355352 TI - Applicability of a video intervention to increase informed decision making for prostate-specific antigen testing. AB - PURPOSE: To evaluate the applicability of an evidence-based video intervention to promote informed decision making for prostate cancer screening among African American men with different levels of health literacy. METHODS: Forty nine African American men participated in interviewer-administered, pretest and posttest interviews between January and March 2008. Health literacy status was assessed with the Test of Functional Health Literacy in Adults. Repeated measures analysis of covariance (ANCOVA), McNemar or binomial distributions were computed to assess pretest and posttest differences in knowledge. Descriptive statistics were produced to describe participants' perceptions of the information presented in the video. RESULTS: Results indicated that men with functional health literacy had higher mean levels of prostate cancer screening knowledge at baseline than men with inadequate health literacy. The between-group (F2,44= 4.84; p = .013) and within-group (F1,44 = 5.16; p = .028) test results from repeated-measures ANCOVA indicated that preexisting group differences in prostate cancer knowledge had lessened after intervention exposure. Nearly all men rated the information presented in the video as credible (98%), trustworthy (96%), interesting (100%), understandable (94%), and complete (96%). CONCLUSIONS: Results from this exploratory study suggest that the video intervention is suitable for use with African American men with different health literacy characteristics in 2 counties in the greater Florida panhandle region. More research is recommended to evaluate the impact of the intervention on men's intentions to undergo screening and actual screening behavior. PMID- 20355353 TI - Colonoscopy utilization in the Black Women's Health Study. AB - Cancer screening is important for health promotion and is a key element in reducing the disparities in cancer morbidity and mortality. Mortality rates for colorectal cancer are more than 40% higher among African Americans than among other ethnic populations in the United States. The primary objective of the present study is to determine correlates of colonoscopy utilization in the Black Women's Health Study. Our study sample comprised 10992 black women from the Black Women's Health Study whose ages ranged from 50 to 72 years at baseline in 1997; colonoscopy use in the subsequent 8 years was ascertained. The strongest correlate of colonoscopy use was mammography use: women who utilized mammography had 2.5 times the odds of having a colonoscopy, compared with those who never screened for breast cancer. Women who reported having health insurance had 2 times the odds of having a colonoscopy compared with women who did not have health insurance. Higher level of education was also associated with colonoscopy screening. Concurrent promotion of cancer screenings, ie, mammography and colonoscopy, may be a good approach to increasing colonoscopy utilization among women. PMID- 20355354 TI - Nerve conduction studies in patients with ankylosing spondylitis. AB - OBJECTIVES: The objective of this study was to investigate any relationship between peripheral neuropathy and ankylosing spondylitis (AS), and to evaluate the peripheral nervous system of AS patients and disclose any relationship between neuropathy and disease-related parameters. PATIENTS AND METHODS: Thirty two AS patients without any symptoms of neuropathy were prospectively recruited in 2 centers. They were substantially evaluated both for AS and evidence of peripheral neuropathy. Motor and sensory nerve conduction studies with regard to median, ulnar, common peroneal, tibial, and sural nerves were performed. Nerve conduction study results of AS patients were compared with those of 30 healthy subjects. RESULTS: Six patients (18.8%) were diagnosed to have involvement of the peripheral nervous system (5 sensory and 1 sensorimotor), and 7 patients (21.9%) had focal nerve involvements (6 had prolonged median distal sensory latency and 1 patient had slowing of the right ulnar nerve motor conduction velocity at the cubital tunnel). Tibial nerve motor conduction velocity was positively correlated with Schober (r = 0.48, p = .03) and chest expansion tests (r = 0.44, p = .05). Sural nerve sensory action potential amplitude was found to be negatively correlated with age (r = -0.53, p = .02) and disease duration (r = -0.55, p = .02). Ulnar nerve motor conduction velocity at the forearm was positively correlated only with Schober values (r = 0.48, p = .03). CONCLUSIONS: We imply that the peripheral nervous system can as well be involved as the central nervous system in asymptomatic AS patients. Further studies with larger samples and with longer disease duration are awaited to confirm our results and to unravel its clinical relevance. Other types of neuropathies or the burden of several drugs on peripheral neuropathy also remains to be deciphered. PMID- 20355355 TI - Coexistence of medullary sponge kidney and renal AA amyloidosis in a patient with nephrotic range proteinuria. AB - We report a patient with medullary sponge kidney (MSK) who presented with hematuria and nephrotic-range proteinuria. Renal biopsy revealed a diagnosis of renal AA amyloidosis. No secondary factors contributing to renal amyloidosis were demonstrated. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and renal AA amyloidosis. PMID- 20355356 TI - A 3-year medical curriculum. AB - The cost of medical education keeps rising while physician shortages loom, student diversity is threatened, and maldistribution continues to affect the physician workforce. The author discusses the rationale for a 3-year undergraduate medical curriculum with reduced costs and proposes a structure with funding for it. Medical educators may consider the issues raised and continue scholarly discussion to promote sustainable, cost effective medical education to address future physician workforce needs. PMID- 20355357 TI - Hanging in the balance: health, dogma, and the debate over malpractice reform. PMID- 20355358 TI - Ronda S. Henry-Tillman, MD, FACS. AB - Dr Henry-Tillman was recently appointed as a member of the Advisory Committee on Research on Women's Health at the National Institutes of Health (NIH). This committee assists the Office of Research on Women's Health (ORWH) and the NIH in addressing scientific, legal, and ethical issues affecting the health of the nation's women through biomedical and behavioral research and related career opportunities. The ORWH was established in 1990 by the NIH and statutorily mandated by Congress in 1993 as a mechanism for eliciting advice and recommendations on priority issues affecting women's health research. Advisory committee members are expected to provide guidance in such areas as refinement of the NIH's women's health research agenda, exploration of questions regarding gender difference in clinical drug trials, development of methodologies that enhance research on health needs of women, and monitoring the inclusion of women in clinical trials funded by the NIH. The director of the Office of Research on Women's Health is Dr Vivian W. Pinn, former president of the National Medical Association. PMID- 20355359 TI - Tropomyosin or not tropomyosin, what is the relevant allergen in house dust mite and snail cross allergies? AB - Since tropomyosin is cross reactive in many arthropods, it was assumed that this highly conserved protein could be responsible for cross reactions in house dust mite (HDM) allergic patients who experienced adverse reactions after crustacean and mollusc ingestion. Here we report two clinical cases where the role of tropomyosin is a matter of debate. In the first case, the clinical history, as well as the results of in vivo and in vitro investigations, are in favour of a shrimp allergy without any snail allergy in a patient sensitized to HDM. In the second, the clinical history and the cutaneous tests are in favour of an allergy to snails without any allergy to shrimps in a patient suffering from HDM allergies. The clinical presentation is different in shrimp and snail allergies. In shrimp allergy, symptoms are mainly urticaria or angio-oedema. In snail allergies, adverse reactions are especially severe asthma. Shrimp tropomyosin is a dominant allergen in crustaceans whereas has a much less prominent role in HDM sensitization. Cross reactivities between HDM and snails have been confirmed by inhibition experiments. However, tropomyosin appears to be a minor allergen or even is not involved in snail allergy. It is necessary to clarify the allergens shared between HDMI and snails. The effects of HDM immunotherapy in snail allergy are questioned. Knowledge of taxonomy can contribute to more precise evaluation of cross reactivities between crustaceans and molluscs. PMID- 20355360 TI - Specific oral tolerance induction for food. A systematic review. AB - BACKGROUND: Specific oral tolerance induction (SOTI) is a new therapeutic approach in the treatment of persistent food allergy. OBJECTIVE: The purpose of this article is to systematically review the literature in order to identify, appraise, and synthesize the evidence about SOTI efficacy and safety. METHODS: A comprehensive search for citations was conducted on May 2, 2009 using MEDLINE via PubMed. Randomized controlled trials (RCTs) including subjects of any age were considered. All these studies were assessed, discussed in details and evaluatedfor quality by authors in a standardized independent way. RESULTS: 15 clinical trials were found. Of these, six trials met the inclusion criteria: three were open label RCT, three were double blind placebo controlled RCT. Two were conducted using sublingual immunotherapy, four using oral desensitization. Overall, the methodological quality of the studies was sufficient. The mean Jadad score of the studies was 3.33 (range = 2-5). Main characteristics and results of the studies were showed and discussed. CONCLUSIONS: SOTI seems to be a possible approach to accelerate the development of tolerance in children affected by food allergy. However, other studies are needed to clarify which is the best treatment and protocol to follow in order to reduce the adverse events and to increase the percentage of success, before thinking that SOTI might be part of the clinical practice. PMID- 20355361 TI - Detection of a novel 20 kDa shrimp allergen showing cross-reactivity to house dust mites. AB - BACKGROUND: Allergy to crustacean shellfish is one of the most common IgE mediated food allergies, and tropomyosin has been identified as the major allergen. However, not all subjects affected by this allergy are IgE-positive to tropomyosin. AIMS: To evaluate whether sera of patients with shrimp allergy but negative for tropomyosin react to other allergen(s); and to evaluate the role such allergen(s) may play in cross-reactivity between crustaceans and house dust mites (HDMs). METHODS: Three different pools of sera-one from subjects with shellfish allergy and HDMs positivity, but negative for recombinant and native tropomyosin (rPen a 1 and nPen m 1) (Pool 2); a second from subjects with tropomyosin and HDMs positivity (Pool 1); and the last from subjects allergic only to HDMs (Pool 3) were submitted to immunoblotting. Subsequently, a 20 kDa protein- enriched fraction of shrimp extract was used at two different concentrations (10 and 100 microg/mL) to pre-absorb the Pool 2 serum and to evaluate, by ELISA assay, the level of inhibition on shrimp and HDMs-coated wells, respectively. RESULTS: The Pool 2 serum showed IgE reactivity against a 20 kDa component. Its pre-absorption with an enriched fraction of 20 kDa protein caused an inhibition of 56% in IgE binding to shrimp extract at a concentration of 100 microg/mL, and of 14% and 35% to HDMs extract at concentrations of 10 and 100 microg/mL, respectively, as measured by ELISA assay. CONCLUSIONS: The 20 kDa component seems to be a new crustacean allergen and it could play a role in cross reactivity with HDMs. PMID- 20355363 TI - A special issue on carbon nanotubes. There's plenty of room at the bottom... in the CNT basement strengthen the foundation before erecting the sky-tower. PMID- 20355362 TI - Epinephrine autoinjector prescription in food-allergic adults: symptom-based only or allergen-based also? An Italian multi-centre study. AB - BACKGROUND: Epinephrine is the treatment of choice for acute food-allergic reactions but existing guidelines state that it should be prescribed uniquely to patients who already experienced at least one food-induced anaphylactic episode. OBJECTIVE: We investigated whether in Italy epinephrine auto-injector is prescribed uniquely following the existing guidelines only, or is allergen informed as well (i.e., based on the potential risk associated with sensitization to certain food allergens), and hence preventive. METHODS: 1110 adult patients (mean age 31 years; M/F 391/719) with food allergy seen at 19 allergy outpatient clinics were studied. Patients with a history of probable anaphylaxis were identified. Subjects were classified as having primary (type 1) and/or secondary (type 2) food allergy and were divided into several subgroups based on the offending allergen/food. Epinephrine prescriptions were recorded and analyzed both as a whole and by sensitizing allergen. RESULTS: Epinephrine was prescribed to 138/1100 (13%) patients with a significant difference between subjects with type-1 and type-2 food allergy (132/522 [25%] vs. 6/629 [1%]; p < 0.001). The epinephrine group included most patients with a history of anaphylaxis (55/62 [89%]) or emergency department visits 106/138 (77%). In some specific subsets, namely fish-, tree nuts-, and lipid trasfer protein (LTP)-allergic patients, epinephrine was prescribed to patients without a history of systemic allergic reactions. CONCLUSIONS: Italian allergy specialists prescribe epinephrine auto injectors both on the basis of clinical history of severe reactions and on a critical analysis of the hazard associated with the relevant protein allergens, which suggests a good knowledge of allergens as well as acquaintance with the guidelines for prescription of emergency medication. PMID- 20355364 TI - Carbon nanotube: the inside story. AB - Carbon nanotubes (CNTs) were serendipitously discovered as a byproduct of fullerenes by direct current (DC) arc discharge; and today this is the most wanted material in the nanotechnology research. In this brief review, I begin with the history of the discovery of CNTs and focus on CNTs produced by arc discharge in hydrogen atmosphere, which is little explored outside my laboratory. DC arc discharge evaporation of pure graphite rod in pure hydrogen gas results in multi-walled carbon nanotubes (MWCNTs) of high crystallinity in the cathode deposit. As-grown MWCNTs have very narrow inner diameter. Raman spectra of these MWCNTs show high-intensity G-band, unusual high-frequency radial breathing mode at 570 cm(-1), and a new characteristic peak near 1850 cm(-1). Exciting carbon nanowires (CNWs), consisting of a linear carbon chain in the center of MWCNTs are also produced. Arc evaporation of graphite rod containing metal catalysts results in single-wall carbon nanotubes (SWCNTs) in the whole chamber like macroscopic webs. Two kinds of arc method have been developed to produce SWCNTs: Arc plasma jet (APJ) and Ferrum-Hydrogen (FH) arc methods. Some new purification methods for as-produced SWCNTs are reviewed. Finally, double-walled carbon nanotubes (DWCNTs) are also described. PMID- 20355365 TI - Chemical vapor deposition of carbon nanotubes: a review on growth mechanism and mass production. AB - This review article deals with the growth mechanism and mass production of carbon nanotubes (CNTs) by chemical vapor deposition (CVD). Different aspects of CNT synthesis and growth mechanism are reviewed in the light of latest progresses and understandings in the field. Materials aspects such as the roles of hydrocarbon, catalyst and catalyst support are discussed. Many new catalysts and new carbon sources are described. Growth-control aspects such as the effects of temperature, vapor pressure and catalyst concentration on CNT diameter distribution and single or multi-wall formation are explained. Latest reports of metal-catalyst-free CNT growth are considered. The mass-production aspect is discussed from the perspective of a sustainable CNT technology. Existing problems and challenges of the process are addressed with future directions. PMID- 20355366 TI - Simulated ultra-fast phenomena in photo-excited carbon nanotube. AB - Ab-initio simulations to explore photo-induced dynamics in nanotubes are presented. By using the time-dependent density functional theory, simulations of electron-ion dynamics in nanotubes were performed with aid of supercomputers. From the simulation results, efficient methods of detection of structural defects and elimination of oxygen impurities from nanotubes are proposed. Furthermore, hot-carrier decay process and modulation of optical field in nanotubes are analyzed. In this review, the computational scheme and the simulation results are introduced. PMID- 20355367 TI - Studies on carbon nanotubes and fullerenes under extreme conditions. AB - Ion beam irradiation of materials can cause defect creation as well as defect annealing depending on the ion beam parameters such as ion fluence and the energy loss of ions in materials. In present review, we report the behaviour of carbon nanotubes under exteme conditions such as laser irradiation and ion irradiation. The reorientation of the crystalline planes in confined single crystal nickel nanorods inside carbon nano tube, induced by heavy ion irradiation, is reported. Axial buckling of nickel nanorods as well as walls of carbon nano tubes in nickel encapsulated carbon nano tubes under swift heavy ion irradiation at high fluence is observed. At high fluence, amorphization of nickel nanorods inside carbon nanotubes is also observed. Axial buckling and amorphization under ion irradiation at high fluence are dependent on the number of walls in carbon nanotubes. High resolution transmission electron microscopy was used to investigate the reorientations, buckling and amorphization of metal filled nanotubes. Synthesis of carbon nanowires by ion irradiation of fullerene and their field emission properties with comparison to that of unirradiated and irradiated carbon nanotubes are reported. An international scenario with future prospects of ion beam studies in carbon nanotube is briefed. PMID- 20355368 TI - Effect of vaporization temperature on the diameter and chiral angle distributions of single-walled carbon nanotubes. AB - Pulsed laser vaporization synthesis of single-wall carbon nanotubes on Co/Ni and Rh/Pd catalysts was explored with respect to variations in the production temperature. The nanotube type populations were determined via photoluminescence, UV-Vis-NIR absorption and Raman spectroscopy. It was found that lowered production temperature leads to smaller nanotube diameters and exceptionally narrow (n, m) type distributions, with marked preference towards large chiral angles for both catalysts. Interestingly, larger nanotube diameters tend to be associated with larger chiral angles. These results demonstrate that PLV production technique can provide at least partial control over the nanotube (n, m) populations. In addition, these results have implications for the understanding the nanotube nucleation mechanism in the laser oven. SWCNT synthesized at lower temperatures appear quite attractive as a starting material for nanotube type separation experiments. PMID- 20355369 TI - Immobilization of tyrosinase in carboxylic and carbonyl group-modified MWNT electrode and its application for sensing phenolics in red wines. AB - Tyrosinase-immobilized biosensor was fabricated based on PAAc-g-MWNT and PMAn-g MWNT, respectively. The poly(acrylic acid)-grafted multi-wall carbon nanotubes, PAAc-g-MWNT, and poly(maleic anhydride)-grafted multi-wall carbon nanotube, PMAn g-MWNT, were prepared by radiation-induced graft polymerization of acrylic acid (AAc) and maleic anhydride (MAn) on the surface of MWNT. The biosensor was prepared on ITO glass electrode by coating of chitosan solution with tyrosinase immobilized PAAc-g-MWNT and PMAn-g-MWNT, respectively. The sensing ranges of the tyrosinase-immobilized biosensor based on PAAc-g-MWNT and PMAn were in the range of 0.2-0.9 mM concentration and in the range of 0.1-0.5 mM for phenol in phosphate buffer solution, respectively. Optimal pH and temperature conditions for sensing various phenolic compounds with tyrosinase-immobilized biosensor were determined. Total phenolic content for three commercial red wines on tyrosinase immobilized biosensor were also determined. PMID- 20355370 TI - A new material with atomized cobalt-multiwalled carbon nanotubes: a possible substitute for human implants. AB - A new material composed of atomized cobalt-multiwalled carbon nanotube has been produced and characterized by thermogravimetric analysis and polarization studies to estimate its lifetime. This does not show cobalt thermal oxidation suggesting that it is confined inside the carbon nanotube matrix. The density functional calculations in the literature predict a strong interaction leading to higher hybridization of cobalt atom and carbon nanotubes. A detailed investigation of the corrosion measurements shows that the new material of thickness 0.8 mm, 1 mm, 1.5 mm and 2 mm would last for 31, 39, 60 and 79 years and it would substitute with cobalt-chromium alloy that is used as a load bearing implant for patients with knee pain or partial denture implant. PMID- 20355371 TI - Fabrication process of carbon nanotube field effect transistors using atomic layer deposition passivation for biosensors. AB - Fabrication process of the carbon nanotube (CNT) field effect transistors (FETs) for biosensors was studied. Atomic layer deposition (ALD) of HfO2 was applied to the deposition of the passivation/gate insulator film. The CNT-FETs did not show the drain current degradation after ALD passivation even though the passivation by Si3N4 deposited by plasma-enhanced chemical vapor deposition (PECVD) resulted in a significant drain current decrease. This indicates the advantage of the present ALD technique in terms of the damage suppression. The biosensing operation was confirmed using thus fabricated CNT-FETs. PMID- 20355372 TI - Preparation and mechanical properties of rubber composites reinforced with carbon nanohorns. AB - Nitrile butadiene rubber (NBR) composites with single-wall carbon nanohorns (SWNHs, or simply NHs), hole-opened NHs (h-NHs), and carbon black (CB), the most commonly used nanocarbon rubber filler, were prepared, and their mechanical properties were compared. The NBR composites with h-NHs (NBR/h-NH) showed higher tensile strength than those with NHs (NBR/NH), and the tensile strength of NBR/h NH or NBR/NH was much greater than those of the NBR composites with CB (NBR/CB). At 5 parts per hundred of rubber (phr), the tensile stresses at break of NBR/h-NH was about 1.8 times larger than those of NBR/CB, and the strain at the break, 1.2 times larger. Similarly, at 20 phr, both the tensile strength and strain at the break of NBR/h-NH were 1.4 times larger than those of NBR/CB. NBR/NH showed the highest hardness while having the smallest specific gravity. The present results indicate that NHs and h-NHs have much superior reinforcement effects to CB for NBR rubber matrix. PMID- 20355373 TI - Efficient solubilization of single-walled carbon nanotubes using tea solutions. AB - Here we describe the finding that oolong tea and black tea act as excellent carbon nanotube solubilizers to produce individually dissolved single-walled carbon nanotubes (SWNTs), which have been revealed using visible-near IR absorption, photoluminescence and Raman spectroscopy as well as AFM study. The oolong tea solution has a tendency to individually dissolve metallic SWNTs that can be detected by 514 nm-excition, and in solution, the (11,3)SWNTs enriched and (11,0)SWNTs that are contained in as-produced SWNTs were very few. Black tea solution shows similar tendency, while the separation performance was weaker compared to that of the oolong tea. We also used epigallocatechin gallate to solubilize the SWNTs and shed light on the mechanism of the SWNT dissolution. Tea contains numerous components with antioxidant activities; therefore biological and biomedical applications using the present soluble nanotubes might be of interest. PMID- 20355374 TI - Growth of carbon nanotubes on silicon carbide fabric as reinforcement for SiC/C composites. AB - Carbon nanotubes (CNTs) have been grown on conventional silicon carbide (SiC) fabric by the catalytic chemical vapour deposition (CCVD) technique. These hybrid reinforcements have been used to develop Silicon carbide-carbon nanotube-carbon matrix mini-composites (SiC/CNTs/C) by chemical vapour infiltration (CVI) method. The microstructures of these hybrid materials and their composites have been studied using scanning electron microscope (SEM), transmission electron microscope (TEM) and Raman spectroscope. The microstructure of the carbon matrix has been compared with the silicon carbide-carbon matrix composites (SiC/C) made with SiC fabric alone. It has been found that the carbon matrix exhibit orientation circumferentially around the SiC fibers. In case of composites with CNTs coated SiC fibers, the carbon matrix is found to get infiltrated within the bundles of CNTs whereas at distance away from the CNTs, the matrix is found to be oriented circumferentially around the SiC/CNT bundles. SiC/CNT/C composites are found to exhibit inherent intrabundle porosity and lower density. PMID- 20355375 TI - Thermal and electronic properties of macroscopic multi-walled carbon nanotubes blocks. AB - Massive carpets of well packed, vertically aligned and very long multiwall carbon nanotubes were synthesized by an efficient thermal Chemical Vapour Deposition process. Electrical properties of the material were evaluated, both in terms of "global" characteristics (bulk resistivity) and in terms of "local" properties (Scanning Tunnel Spectroscopy measurements) for as-grown and annealed at different temperatures samples. The behaviour of bulk resistivity as a function of temperature was evaluated in the range 3-300 K, with a four-probe technique. The resistivity shows a linear dependence with the square root of temperature in the investigated range. From the electrical analyses, it was found that the quality of the MWNTs was improved by the annealing process, since the resistivity decreases. Heat transport properties were evaluated by the laser flash technique in order to study thermal diffusivity. Moreover high temperature behavior of the specific heat capacity of single and multi-wall carbon nanotubes, was measured up to 800 K with a Differential Scanning Calorimeter. PMID- 20355376 TI - Nanoimmiscibility: Selective absorption of liquid methanol-water mixtures in carbon nanotubes. AB - Despite the continuing research interests in CNT-liquid systems, the microscopic structure and transport behavior of liquid mixtures in carbon nanotubes (CNTs) remain poorly understood. Methanol and water liquids are completely miscible across the entire range of concentration; however, recent research reveals that they are immiscible at a molecular level. In this work, we carried out classical molecular dynamics to study the molecular distribution, structure ordering, clustering and transport behavior of liquid methanol-water mixtures within CNT confinement. We found that CNTs preferentially absorbed methanol over water molecule even though the latter has a smaller molecular size, indicating that chemical effect such as molecular hydrophilicity plays a crucial role in the molecular absorption of CNTs. Due to the selective absorption of CNTs, methanol aqueous solution changes from microscopically immiscible to macroscopically immiscible at nanoscale. This nanoscale immiscibility may be utilized in various applications of CNTs including direct methanol fuel cells, nanosensors, molecular sieves, nanofluidic chips, and capsules for drug delivery. PMID- 20355378 TI - Development of magnetically aligned single-walled carbon nanotubes-gelatin composite films. AB - Magnetically aligned and highly dispersed single-walled carbon nanotubes (SWNTs) gelatin composite films were fabricated on a quartz substrate of newly designed disassemblable sample cells. After an SWNTs-gelatin composite sol in each sample cell was exposed to vertical DC magnetic fields to 28 T during the sol-gel transition, a side plate with a polytetrafluoroethylene film attached to the inner surface was removed from the sample cell carefully, and the composite gel left on the other side plate made of quartz was dehydrated in a nonmagnetic circumstance. We have found that the alignment of SWNTs is retained in uniform composite films obtained after the nonmagnetic drying process. Both polarized absorption measurements and polarized Raman scattering measurements were performed in order to confirm the alignment of SWNTs in the composite films consistently. The optical anisotropy of the composite films increased somewhat superlinearly as a function of the magnetic field applied during the sol-gel transition and reached to 0.13 at 28 T. The nonmagnetic drying process would make it easy to apply higher magnetic fields to the fabrication of aligned SWNTs films as it consumes resources to keep operating high field magnets such as hybrid magnets during the drying process. PMID- 20355377 TI - Poly(3-octylthiophene)/fullerene heterojunction solar cell incorporating carbon nanotubes. AB - Here, we report incorporation of multiwalled carbon nanotubes (MWNTs) in Poly(3 octylthiophene)/fullerene heterojunction solar cells. Multi-walled carbon nanotubes (MWNTs) were functionalized by oxygen plasma treatment. Photoelectron spectroscopy study of oxygen plasma treated MWNTs shows surface modification with hydroxyl and carboxyl groups. Plasma treated MWNTs were combined with Poly(3 octylthiophene) and solar cell was fabricated with the structure Au/P3OT + MWNTs/C60/FTO. Fabricated device shows short circuit current density (Jsc) open circuit voltage (Voc), fill factor and conversion efficacy as 0.04 mA/cm2, 0.355 V, 21% and 0.003%. Solar cell fabricated with incorporation of MWNTs shows much better device performance, then that of the device without MWNTs. MWNTs in the polymer composite act as exciton dissociation site and provide efficient hole transportation, and thereby improving device performance. PMID- 20355379 TI - Modifying surface structure to tune surface properties of vertically aligned carbon nanotube films. AB - We report a simple etching process to modify surface of vertically aligned carbon nanotube (VACNT) arrays for their applications in superhydrophobic surface, field emission display, and sun energy conversion, etc. At a high temperature (700-800 degrees C), very low concentration water vapor in presence with Ar and hydrogen flow can be a weak oxidant, and mildly etch nanotube tips without damaging their walls. This process can be performed right after the CNT growth process. Surface of nanotube arrays becomes multi-tiered nanotube patterns with open-ended nanotubes standing straightly. Surface morphology of nanotube arrays can be tuned by changing the etching time. Water droplets on a modified nanotube surface show a large contact angle and sliding angle, which make the etched nanotube film suitable for application such as small amount liquid transport. Light absorption measurement indicated that surface roughness has no effect to improve the light absorption, indicating a different mechanism from other black material. The surface modified nanotube arrays have much increased field enhancement factor in our field emission test, showing the better field emission ability of the nanotube arrays with open tips. PMID- 20355380 TI - Hydrogen adsorption in several types of carbon nanotubes. AB - In this work, we aim to study the hydrogen adsorption in several kinds of carbon nanotubes grown under different process conditions and to correlate the findings with the morphological microstructure and physical properties of these materials. The growth conditions and the behaviour with respect to hydrogen interaction of various carbon nanotubes are discussed, to establish microstructure-process property relationships. In particular, we have analyzed several types of carbon nanotubes, namely one single-walled and five multi-walled having different tube diameter (due to different deposition techniques and conditions), different defectiveness and submitted to different surface treatments. To better understand the differences among the various samples, they have been investigated using field emission scanning electron microscopy and high resolution transmission electron microscopy for the morphological and structural characteristics, thermo gravimetric analysis for the sample purity and Brunauer-Emmett-Teller analysis for the surface area. The experimental measurements on the ability of the different types of carbon nanotubes to adsorb and/or releasing hydrogen have been performed at 77 K with a volumetric Sievert analytical tool. Our findings clearly demonstrate a direct correlation between the exposed surface area and adsorbed hydrogen capacity, which confirms their linear relationship observed previously. For instance, single-walled nanotubes with surface area density of approximately 800 m2/g have showed hydrogen storage of approximately 1.7 wt% at a pressure of 35 atm. Adsorption process seems to be perfectly reversible. The adsorption values have been compared with a simple model, in order to evaluate the potentialities for carbon-based nanomaterials in future hydrogen storage applications. PMID- 20355381 TI - Effective patterning of metal nanoparticles on sapphire surface for aligned growth of single-walled carbon nanotubes. AB - We studied patterning of metal nanoparticle catalyst on sapphire (alpha-Al2O3) substrates to grow horizontally-aligned single-walled carbon nanotubes (SWNTs) from defined positions. Various modifications of sapphire surface were investigated for effective adsorption of iron oxide nanoparticles. We found that phosphoric acids bind to sapphire surface and enhance the adsorption of the nanoparticles. This surface modification enabled effective patterning of nanoparticle via electron beam lithography. The small nanoparticles with a mean diameter of 5 nm tended to diffuse at high temperature during the nanotube growth, while the large particles with 12 nm mean diameter mostly stayed at the same position giving aligned SWNTs grown from the catalyst pattern. PMID- 20355382 TI - Electrochemical performance of amorphous carbon nanotube as anode materials for lithium ion battery. AB - Amorphous carbon nanotubes (ACNTs) showed the different structure with crystal carbon nanotubes, such as single-walled and multi-walled carbon nanotubes due to their unique tube walls. The tube wall of ACNTs is comprised of many single layer graphene sheets which present long-distance disorder and short-distance order. Herein, we mainly studied the electrochemical property of ACNTs as anode materials for lithium ion secondary batteries and the mechanism of intercalation lithium. The electrochemical performances of as-grown and oxidized ACNTs were tested by two-electrode cell. The results indicate that the reversible capacity of ACNTs oxidized at 300 degrees C reaches 530 mAh/g and after the first 5 cycles the capacity remains 93%. The intercalation Li of ACNT include the inner wall and the side wall between graphene sheets. ACNTs offer a new exciting alternative to the traditional materials used for fabrication of lithium ion secondary batteries. PMID- 20355383 TI - Optical spectroscopic studies of thermally coalesced single-walled carbon nanotubes. AB - Changes in the optical properties of thermally coalesced single-walled carbon nanotubes (SWCNTs) caused by heat treatment between 1300 and 2800 degrees C in argon, have been monitored using optical absorption and photoluminescence spectroscopy. For SWNTs heat treated at 1900 degrees C, we found a complete disapperance of small-diameter tubes (<1.0 nm) as well as the appearance of enlarged, defective tubes. The decreased sp2/sp3 ratio for tubes heat treated below 2100 degrees C suggests that adjacent small-diameter SWNTs transform into energetically stable larger-diameter SWNTs by the presence of structural non sp2 defects. PMID- 20355384 TI - Transmission electron microscope observation of interface structures of graphene on 6H-SiC. AB - High-resolution transmission electron microscopic cross-sectional observations of graphene-on-SiC(0001) were carried out to directly observe the interface structure. A first principles calculation allowed us to understand the interface structures and their electronic states. Our observations revealed a metastable transitional interface structure formed by decomposition of a single SiC bilayer as well as complete honeycomb graphene formed by the decomposition of three SiC bilayers. The calculations further showed that the differences in the interface structures should strongly influence the electronic states, producing either metallic or semiconducting behavior. These results may help to resolve the controversy over the electronic states of graphene-on-SiC, and promote more accurate band-gap engineering via surface decomposition. PMID- 20355385 TI - Novel in-situ decoration of single-walled carbon nanotube transistors with metal nanoparticles. AB - The carbon nanotube-metal nanoparticle complex has attracted a lot of research interest because of their potential applications in catalysis and gas sensing. Here we introduce a novel electrochemical method to realize in-situ decoration of single-walled carbon nanotube field effect transistors (CNT-FET) with metal nanoparticles using a sacrificial electrode. In this process, metal atoms are first ionized into an electrolyte solution by applying a potential difference between the sacrificial electrode and the grounded source/drain electrodes connecting the nanotube of the CNT-FET. The positive metal ions migrate under the influence of the electric field, and deposit on the grounded nanotube as metal nanoparticles. This method provides for better control over the quantity and size of the deposited nanoparticles compared to other decoration methods. We demonstrate successful deposition of Au and Ag nanoparticles on carbon nanotube field effect devices, with the quantity and size of the nanoparticles varying as a function of the applied potential. We show that the metal nanoparticle size can vary from 10 nm to over 300 nm, and the spatial distribution can change from very scarce decoration to a near continuous coating. Such metal nanoparticles have potential applications in chemical sensors, as they interact with gas molecules and generate an electrical signal in the nanotube, which can be detected. They can also be explored as biological anchoring sites for bio-functionalization of the nanotube, which is critical to developing highly sensitive and selective bio sensors. PMID- 20355386 TI - Highly dispersed Pt-Ni nanoparticles on nitrogen-doped carbon nanotubes for application in direct methanol fuel cells. AB - Binary Pt-Ni alloyed nanoparticles supported on nitrogen-doped carbon nanotubes (NCNTs) have been facilely constructed without pre-modification by making use of the active sites in NCNTs due to the N-participation. So-obtained binary Pt-Ni alloyed nanoparticles have been highly dispersed on the outer surface of the support with the size of about 3-4 nm. The electrochemical properties of the catalysts for methanol oxidation have been systematically evaluated. Binary Pt-Ni alloyed composites with molar ratio (Pt:Ni) of 3:2 and 3:1 present enhanced electrocatalytic activities and improved tolerance to CO poisoning as well as the similar stability, in comparison with the commercial Pt/C catalyst and the monometallic Pt/NCNTs catalysts. These results imply that so-constructed nanocomposite catalysts have the potential for applications in direct methanol fuel cells. PMID- 20355387 TI - Parametric study of alcohol catalytic chemical vapor deposition for controlled synthesis of vertically aligned single-walled carbon nanotubes. AB - In this study we examine catalyst preparation and chemical vapor deposition (CVD) parameters related to synthesis of single-walled carbon nanotubes (SWNTs) by alcohol catalytic CVD. We show that modifying the catalyst recipe considerably changes the average SWNT diameter, and vertically aligned arrays with an average diameter of 1.5 nm were obtained. The height of vertically aligned SWNT arrays can be significantly enhanced by surface modification of the substrate prior to dip-coating, although this produces SWNTs with larger diameters at the root of the array. We demonstrate patterned growth by combining this method with suppression of SWNT synthesis by formation of a hydrophobic surface. We also consider the effects of ethanol flow rate and thermal decomposition on the chemical environment at the substrate. The growth process is considerably altered by the extent of ethanol decomposition, with sudden termination of the growth occurring in the extreme low-flow (complete decomposition) case. PMID- 20355388 TI - Electric and mass transport of a carbon nanotube encapsulating a copper nano-rod studied by in-situ transmission electron microscopy. AB - Electric properties and current-induced structural changes of carbon nanotubes (CNTs) encapsulating copper nano-rods were studied by in-situ transmission electron microscopy (TEM). The diameter and the length of a copper filled CNT were 18 nm and 256 nm, respectively. The thickness of the graphite layer was about 1 nm. The bias voltage was applied between the two ends of the CNT inside the TEM, and the current as well as TEM images were recorded simultaneously. At a bias voltage of 1.4 V, the current increased to 10 microA, corresponding to a current density of 4.0 x 10(6) A/cm2, and at the same time the nano-rods inside the CNT started to move to an end of the CNT. After the movement of the nano rods, an empty CNT was left. Resistivities of the CNT and the copper nano-rod were measured to be 3.0 x 10(-5) ohm m and 1.2 x 10(-4) ohm m, respectively. PMID- 20355389 TI - Splitting and flattening of helical carbon nanofibers by acid treatment. AB - Helical carbon nanofibers (HCNFs), such as the carbon nanocoil (CNC) and the carbon nanotwist (CNTw), were synthesized by catalytic chemical vapor deposition using a substrate. HCNFs are classified into round and angular types according to the fiber cross-sections. When four types of HCNFs (round-type CNC and CNTw, angular-type CNC and CNTw) were acidified in a 30% hydrogen peroxide solution, only the angular type CNC was found to show a drastic shape change. The shape change observed was a splitting followed by a flattening of the angular type CNCs. The CNC was split into two or three thinner flat fibers. As a function of the treatment temperature, the weight of the CNCs decreased above 80 degrees C and the CNCs were etched effectively at 140 degrees C. The longer the reaction time the lower the weight of the CNCs, and the weight loss reached a saturation point when the reaction time was greater than 45 min at 140 degrees C. The splitting and flattening of the CNC occurred during the weight loss process. To analyze the CNC structure, electron tomography of the as-grown and acid-treated CNCs was obtained using a computerized tomograph system with transmission electron microscopy (TEM). The 3D-images were constructed using the TEM images collected at different tilt angles. The 3D image reconstructions showed that the CNCs had a tubular structure and were composed of several helical fibers which act as frames. PMID- 20355390 TI - Investigation of CNT growth by substrate temperature control using thermal CVD method. AB - Influence of metal catalyst (Fe) surface condition was investigated for the growth of carbon nanotubes (CNTs). Surface condition of 5 nm thick Fe coated on Si substrate was changed by varying substrate temperature during the CNTs synthesis in a thermal CVD method. Acetylene and argon were used as precursor and carrier gas, respectively, for the synthesis of CNTs. After the growth, the CNTs were removed from the substrate and the post-growth condition of the substrate surface was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Unlike the case of untreated Fe-coated Si substrate, XPS analysis shows Si peaks from the thermal treated substrate/samples, which indicates the formation of Fe nanoparticles. AFM results indicate that 750 degrees C is optimum temperature for the nanoparticle formation. Moreover, SEM results show that 700 degrees C is optimum temperature for the CNTs synthesis. The results of this study clarify that the optimum temperature for nanoparticle formation and CNT synthesis are different. PMID- 20355391 TI - Synthesis of single-walled carbon nanotubes through micropores of surface-treated zeolites by catalyst-supported chemical vapor deposition. AB - Cobalt nanoparticle-loaded Y-type zeolite (HSZ390HUA) without outer-surface Co aggregates is successfully prepared by Co impregnation reaction followed by surface treatment using tetraethylammoniumbromide having larger molecule size than the orifice size of the Y-type zeolite. Single-wall carbon nanotubes (SWCNTs) have been synthesized by ethanol catalyst-supported chemical vapor deposition at 973 K for 10 min using as-produced and surface-treated Co-loaded zeolites. The SWCNTs synthesized are characterized by transmission electron microscopy, Raman spectroscopy and photoluminescence spectroscopy. The products synthesized by using the as-produced Co-loaded zeolites are mostly multi-wall carbon nanotubes (MWCNTs) with larger diameter than the orifice of zeolite and carbon nanocapsules (CNCs). In contrast, SWCNTs with diameters of 0.66-0.85 nm, which are approximately the same as that of the orifice size, are selectively synthesized by using the surface-treated Co-loaded zeolites. PMID- 20355392 TI - Catalytic effect of different forms of iron in purification of single-walled carbon nanotubes. AB - In the arc plasma jet (APJ) method, a large amount of soot including single wall carbon nanotubes (SWNTs) can be produced in a short time. However, as-grown soot contains a lot of impurities, such as metallic particles used as catalyst and amorphous carbon. Hence it is necessary to purify the soot to obtain pure SWNTs. The biggest problem in purifying APJ-SWNTs is how to remove the thick amorphous carbon covering the catalyst metal particles. By refluxing APJ-SWNTs in hydrogen peroxide using iron particle as catalyst, it can be purified. The added fine particle of pure iron is found to be effective. Then, we examine whether SWNTs can be purified more effectively by adding solution containing the Fe ion instead of the iron particle. We used iron (III) nitrate nonahydrate, hydrogen peroxide decomposing agent which contains catalase and ammonium iron (II) sulfate hexahydrate. In the case of iron (III) nitrate and catalase, purification effect is not obvious. Under these conditions hydrogen peroxide was decomposed into H2O and O2, and the hydroxyl radical was not generated. On the other hand, ammonium iron (II) sulfate is effective. Because of existence of Fe2+ in solution Fenton's reaction takes place. Reaction rate is increased at high temperature. Therefore, APJ-SWNT is purified more effectively if refluxed in hydrogen peroxide using ammonium iron (II) sulfate as catalyst. PMID- 20355393 TI - Effect of buffer thickness on single-walled carbon nanotube growth using aluminum oxide buffer layer with alcohol gas source method. AB - Aluminum oxide (Al2Ox) buffer layers were employed in carbon nanotube (CNT) growth using an alcohol gas source and Co catalyst. The CNT yield was strongly dependent on the Al2Ox buffer layer thickness. By optimizing the thickness of deposited Al, vertically aligned single-walled nanotubes (SWNTs) were grown on Si substrates, even under an ethanol pressure of 10(-1) Pa. Transmission electron microscopy (TEM) revealed that Co particle size was strongly dependent on Al thickness. Dense Co particles about 2-4 nm in diameter were formed at the optimal Al thickness. Surface flatness of oxide layers was relatively independent of oxide thickness, and could be easily maintained up to the onset of CNT growth. Thus, Al2Ox layers promote formation of nanosized Co particles suitable for SWNT growth, providing a significant enhancement to yield. At the higher Al thickness, the yield was reduced, which was due to the diffusion of Co particles into the Al2Ox layer. Therefore, control of Al thickness is important to obtain efficient CNT growth. PMID- 20355394 TI - Doping of carbon nanotubes using low energy ion implantation. AB - Carbon nanotubes (CNTs) were implanted with thermally decomposed oxygen (O2+) and nitrogen (N2+) ions at an acceleration voltage of 20 V. With a low dose of oxygen ions, the CNT-FET exhibited p-type behaviors with substantial changes in threshold voltage and in the slope of the source-drain current (l(sd)). However, at high dosages, the device exhibited metallic behaviors. After nitrogen doping, we did not observe the effects of electron doping. Instead, nitrogen doping significantly increased l(sd) with no gating effect. Our theoretical results showed that the metallic behavior of nitrogen-doped CNTs arose from the impurity conduction band, which results from the overlapping wave function of the nitrogen impurity. PMID- 20355395 TI - Sensitive G-band Raman features for the electrical conductivity of multi-walled carbon nanotubes. AB - We have studied the structural parameters of catalytically grown highly disordered multi-walled carbon nanotubes that were heat treated at temperatures between 1200 degrees C and 2600 degrees C in an argon atmosphere. Rather than the interlayer spacing or the R value (the intensity of the D band divided by the intensity of the G band), we found that the half width at half maximum intensity of the G band was the most sensitive parameter that is correlated with the altered electrical conductivity of an individual carbon nanotube that had been heat treated at high temperatures. This is because one-dimensional nanocarbons exhibit a preference for two-dimensional structural development along the length of the tube due to the limited mobility of carbon atoms along the circumferential direction. Tubes heat treated at 2200 degrees C exhibited both a high electrical conductivity and an absence of lithium-ion intercalation, and thus are the best conductive filler for the active materials of lithium-ion batteries for long-term stability. PMID- 20355396 TI - Synthesis and in-situ TEM transport measurements of individual GaN nanowires and nanotubes. AB - High-purity GaN nanowires and nanotubes of various morphologies and sizes have been synthesized through epitaxial growth on [001]-oriented sapphire substrates. The GaN nanowires grown on Ni catalyst particles possess an average diameter of approximately 100 nm and rather smooth surface; whereas GaN nanotubes guided by Au particles exhibit large diameters (100-500 nm) and rough surface morphology. The microstructures and crystallography of GaN nanowires and nanotubes were analyzed using a high-resolution transmission electron microscope (HRTEM). For the first time the electrical transport in individual GaN nanowires and nanotubes was in-situ measured inside the microscope. The electrical transport was mainly affected by the nanocrystal quality and nanostructure/contact interfaces. PMID- 20355397 TI - Top-down heating for low substrate temperature synthesis of carbon nanotubes. AB - A top-down heating method to allow for low-temperature large area synthesis of carbon nanotubes using plasma-enhanced chemical vapour deposition is introduced in this paper. The approach utilizes top-down electromagnetic heating rather than conventional heating from a substrate heater under the electrode. A temperature gradient is created between the Ni catalyst surface and the substrate using a metal thermal control barrier layer, on which carbon nanotubes are grown as a function of the bias voltage, hydrocarbon concentrations and growth conditions. The heat during growth is provided by the plasma or energy coupling to the catalyst via top-down heating, which based on the coupled power density and the cooling of the substrate, in addition to the thermal 'barrier layer' properties will dictate the temperature of the growth surface. This unique approach of top down heating with suitable cooling schemes, coupled with thermal barriers allows for the low substrate temperature synthesis of carbon nanotubes, scalable to large areas. PMID- 20355398 TI - Spectroscopic characterization of N-doped single-walled carbon nanotube strands: an X-ray photoelectron spectroscopy and Raman study. AB - We have studied in detail the carbon and nitrogen bonding environments in nitrogen-doped single-walled carbon nanotubes (SWCNTs). The samples consisting of long strands of N-doped SWCNTs were synthesized using an aerosol assisted chemical vapor deposition method involving benzylamine-ethanol-ferrocene solutions. The studied samples were produced using different benzylamine concentrations in the solutions, and exhibited a maximum concentration of ca. 0.3%at of N, determined by X-ray photoelectron spectroscopy (XPS). In general, we observed that the ratio between substitutional nitrogen and the pyridine-like bonded nitrogen varied upon the precursor composition. Moreover, we have observed that the sp2-like substitutional configuration of the C-N bond does not exceed the 50% of the total N atomic incorporation. In addition, we have characterized all these samples using Raman spectroscopy and electron microscopy. PMID- 20355399 TI - Efficient vapor sensors using foils of dispersed nitrogen-doped and pure carbon multiwalled nanotubes. AB - We fabricated vapor sensors using nitrogen-doped (CNx) and pure multi-walled carbon nanotubes (MWNTs), and compared their performance. The sensors were constructed by dispersing the nanotube materials in methanol so as to form millimeter-long foils (nanotube paper), consisting of compact arrays of crisscrossing nanotubes. The devices were characterized by electrical resistance measurements and SEM studies. For CNx-based sensors, we observed that low concentrations of vapors such an acetone, ethanol, and chloroform were efficiently detected within 0.1-0.3 seconds via a physisorption mechanism. This physisorption is explained in terms of a weak interaction of the vapor molecules with the pyridinic sites (N bonded to two carbon atoms) present in the doped tubes. We believe that the methanol used for preparing the foils has a strong effect in saturating substitutional N atoms (N atoms bonded to three carbon atoms) that are also located in the CNx tubes. However, when pure carbon MWNTs were tested as sensors, we witnessed chemisorption of these vapors. First principles density functional calculations confirmed that the gaseous molecules are able to interact with N-doped carbon nanotubes, via a physisorption mechanism, in which pyridine sites play a crucial role. PMID- 20355400 TI - Fabrication and dispersion evaluation of single-wall carbon nanotubes produced by FH-arc discharge method. AB - In this work, we produced SWNTs by a hydrogen DC arc discharge with evaporation of carbon anode containing 1 at% Fe catalyst in H2-Ar mixture gas. This was named as FH-arc discharge method. The as-grown SWNTs synthesized by FH-arc discharge method have high crystallinity. An oxidation purification process of as-grown SWNTs with H2O2 has been developed to remove the coexisting Fe catalyst nanoparticles. As a result, SWNTs with purity higher than 90 at% have been achieved. To exhibit remarkable characteristics, CNTs should be separated from the bundles and kept in homogeneous and stable suspensions. For this purpose, the SWNTs prepared by FH-arc discharge method also have been treated by Nanomizer process with some surfactants. SPM images showed that the SWNTs bundles had become thinner and shorter. PMID- 20355401 TI - Anisotropic polyhedral self-assembly of Ag-CNT nanocomposites. AB - We report the unique assembling behavior of Ag NP supported CNT nanocomposites. Initially Ag NPs were precipitated homogeneously on the walls of SDS-coated CNTs by a NaBH4 chemical reduction and/or photoreduction directly in an aqueous solution. An additional Ag source was subsequently added into the Ag-CNT dispersion and Ag was further reduced using hydroxylamine in a weakly alkaline condition. The morphology of the resulting Ag-CNT nanocomposites strongly depended on the Ag+ ion concentration. Interestingly, an anisotropic polyhedral self-assembly of Ag-CNT nanocomposites was observed when the Ag concentration was increased to 0.1 M (real concentration). PMID- 20355402 TI - Influence of surface roughness on field emission of electrons from carbon nanotube films. AB - Electron field emission properties of a nanotube film are influenced not only by a field enhancement factor of carbon nanotubes (CNTs) beta(CNT) but also by that of film morphology beta(P). A simple method to separate beta(P), and beta(CNT) is proposed by using their different dependences on the cathode-anode distance. Analyses conducted for CNT emitters with rough surface exhibit that beta(P) ranges from 1 to approximately 4.5. The separated beta(CNT) values are in good agreement with the CNT geometries observed by a scanning electron microscope. Variation in beta(P)-values is ascribed to the surface roughness of the CNT films. PMID- 20355403 TI - Influence of Mo on the growth of single-walled carbon nanotubes in arc discharge. AB - In this study, we investigated the role of Mo on the growth of single-walled carbon nanotubes (SWNTs) in arc discharge method. Mo with various concentrations was incorporated into two typical arc systems, namely Ni/Y-He and Fe-Ar/H2. Based on analyses of yield and purity, we found the best concentration of Mo is 0.5 at% in Ni/Y-He system and 0.3 at% in Fe-Ar/H2 system. For both systems, the incorporation of Mo has dramatically increased the yield of soot in their best concentrations. On the contrary, the promotion effects of Mo on purity of SWNTs were not same. Thermal gravimetric analysis showed that with the addition of Mo, the purity of SWNTs did not change effectively for Ni-Y/Mo-He system, but noticeable increment of purity was observed for Fe/Mo-Ar/H2 system from 33 wt% to 50 wt%. Considering on these experimental results, we prove that Mo plays a positive role in arc discharge for the enhancement of SWNTs growth. PMID- 20355404 TI - Structural analyses of high-pressure and high-temperature treated double-walled carbon nanotubes. AB - This paper reports the structural properties of the high-pressure and high temperature (HPHT) treated double-walled carbon nanotubes (DWCNTs) based on Raman, XRD and TEM experiments. It was found that the DWCNTs are more stable toward HPHT treatment than the single-walled carbon nanotubes (SWCNTs). We propose that this is probably because the DWCNTs tend not to be deformed by compression and thereby they are less reactive under pressure compared to SWCNTs. PMID- 20355405 TI - High-quality thin-multiwalled carbon nanotubes synthesized by Fe-Mo/MgO catalyst based on a sol-gel technique: synthesis, characterization, and field emission. AB - We synthesized thin-multiwalled carbon nanotubes (t-MWCNTs) using Fe-Mo/MgO catalyst by citrate precursor method based on a simple sol-gel technique. Synthesis of high-quality t-MWCNTs with uniform diameters was achieved in large scale by catalytic decomposition of methane over Fe-Mo/MgO catalyst prepared under Ar-atmosphere. The produced t-MWCNTs had the outer diameters in the range of 4-8 nm, with a Gaussian average diameter of 6.6 +/- 0.1 nm and wall numbers in the range of of 4-7 graphenes. The product yield of the as-synthesized t-MWCNTs was over 450% relative to the used Fe-Mo/MgO catalyst, and TGA showed purity about 85%. The t-MWCNTs showed the low turn-on field about 1.24 V/microm, corresponding to the current density of 0.1 microA/cm2, and the high emission Current density of 10 mA/cm2 at the applied electric field of 2.6 V/microm. The t MWCNTs indicate good emission stability without any fluctuation of emission current through a lifetime measurement for 20 h. It was confirmed that the field emission performance of t-MWCNTs was similar to DWCNTs and the field emission stability of t-MWCNTs was similar to MWCNTs. PMID- 20355406 TI - Chemical vapor deposited carbon nanotubes for aqueous H2-Cl2 fuel cells. AB - Carbon nanotubes having large surface area is an interesting material to develop H2-Cl2 fuel cell electrodes. The attempts were made to deposit carbon nanotubes on porous substrates by chemical vapour deposition. Turpentine oil (C10H16) was used as a precursor, decomposed at 1100 degrees C reactor temperature. Nickel, platinum, tin, Ni-Pt, Ni-Sn, Pt-Sn, Ni-Pt-Sn catalysts were used to grow carbon nanotubes. Nickel was deposited with electrodeposition, platinum with sputter coater and tin with vacuum deposition technique. The developed electrodes were characterized by XRD, SEM, TEM, FTIR, and resistivity by van-der Pauw method. Carbon nanotubes have been formed for 0.25 N nickel deposited for 45 and 60 min; 0.5 N, 0.75 N and 1 N nickel deposited for 15 to 60 min, at the interval of 15. Ni-Pt, Ni-Sn, Pt-Sn and Ni-Pt-Sn activated carbon also shows the well grown CNTs. Aqueous H2-Cl2 fuel cell performance was tested with these grown carbon nanotubes. 40% KCl with 1067 mohm(-1) cm(-1) conductivity was used as electrolyte. Linear sweep voltametry shows reduction potential for hydrogen gas. Chronoamperometry results show better half cell performance for nickel, deposited with 1 N, 45 min deposition time period; and combination of Ni-Pt-Sn with 140, and 110-100 mA/cm2 stable current density respectively. PMID- 20355407 TI - Growth of aligned MWNT arrays using a micrometer scale local-heater at low ambient temperature. AB - Ambient room temperature growth of aligned multi-walled carbon nanotube arrays on micrometer scale local heaters is demonstrated. High growth rates of up to 8.8 microm per second have been achieved and the growth has been monitored in situ using optical microscopy. The growth starts and ends abruptly over the length of the local heater. The terminal length of the nanotubes shows a clear dependence on growth temperature and small inhomogeneities in temperature across the heater are seen to lead to interesting microstructure of the arrays. The activation energy for growth was seen to be consistent with earlier reports for acetylene growth of nanotubes on iron catalysts. PMID- 20355408 TI - Preparation of platinum nanoparticles on carbon nanostructures using metal organic chemical fluid deposition employing supercritical carbon dioxide. AB - We developed a formation method of platinum (Pt) nanoparticles by the metal organic chemical fluid deposition (MOCFD) employing supercritical fluid (SCF), and demonstrate the synthesis of dispersed Pt nanoparticles on the surface of aligned carbon nanotubes and carbon nanowalls, two-dimensional carbon nanostructures standing vertically on the substrate. By using the SCF-MOCFD employing a supercritical carbon dioxide as a solvent of metal-organic compound ((methylcyclopentadienyl)trimethyl platinum: MeCpPtMe3), highly dispersed Pt nanoparticles of 2 nm size were deposited on the entire surface of carbon nanotubes and carbon nanowalls. The formation of Pt nanoparticles on the surface of carbon nanostructures occurred at relatively low temperatures above 120 degrees C. Furthermore, the number density of Pt nanoparticles increased with the increase of temperature. PMID- 20355409 TI - Optimization of parameters by Taguchi method for controlling purity of carbon nanotubes in chemical vapour deposition technique. AB - The process parameters (viz. temperature of synthesis, type of catalyst, concentration of catalyst and type of catalyst-support material) for controlling purity of carbon nanotubes synthesized by catalytic chemical vapour deposition of acetylene have been optimized by analyzing the experimental results using Taguchi method. It has been observed that the catalyst-support material has the maximum (59.4%) and the temperature of synthesis has the minimum effect (2.1%) on purity of the nanotubes. At optimum condition (15% ferrocene supported on carbon black at the synthesis temperature of 700 degrees C) the purity of nanotubes was found out to be 96.2% with yield of 1900%. Thermogravimetry has been used to assess purity of nanotubes. These nantubes have been further characterized by scanning electron microscopy, transmission electron microscopy and Raman Spectroscopy. Small angle neutron scattering has been used to find out their average inner and outer diameter using an appropriate model. The nanotubes are well crystallized but with wide range of diameter varying between 20-150 nm. PMID- 20355410 TI - New Raman-peak at 1850 cm(-1) observed in multiwalled carbon nanotubes produced by hydrogen arc discharge. AB - The new peak (near 1850 cm(-1)) assigned to carbon linear chain included in the centre of very thin innermost multiwalled carbon nanotubes (MWNTs) has been verified by Raman spectroscopy. These MWNTs were produced by dc arc discharge of pure graphite rods in pure hydrogen gas and existed in the cathode deposit. In this paper, we clarified that the new Raman-peaks could also be observed in the cathode deposit including MWNTs produced by hydrogen dc arc discharge using graphite electrode with added Y or La. By changing the quantity of addition (Y or La), dc arc current and pressure of ambient hydrogen gas, the optimum condition to get maximum intensity of the new Raman-peaks was obtained. For the case of 1 wt% La, dc 50 A, H2 pressure of 50 Torr was found to be optimum, and the intensity of new Raman-peak was even higher than the G-band peak. For the case of 1 wt% Y, dc 50 A, H2 pressure of 50 Torr was optimum, but the intensity of new Raman-peak was weaker than the G-band peak. Transmission electron microscopy observation revealed that the crystallinity of MWNTs produced with pure graphite rod was better than those produced with added Y or La. PMID- 20355411 TI - Ferrocene derived carbon nanotubes and their application as electrochemical double layer capacitor electrodes. AB - We report on the synthesis of carbon nanotubes (CNTs) by direct thermal decomposition of ferrocene (Fe(C5H5)2). Our studies indicate that presence of a small amount of sulfur along with the ferrocene in the decomposition process strongly affects the quality of the CNTs produced and is crucial for obtaining thin diameter nanotubes. Raman spectroscopic investigations suggest that the atomic ratio of sulfur to the total iron plus sulfur content of approximately 0.09 yields CNTs with highly crystalline structure having diameters ranging from 0.85 nm to 1.75 nm. Electrochemical double layer capacitor electrodes fabricated from these CNTs show impressive energy storage properties, capable of delivering a maximum power density of approximately 27 KW/kg and energy density of approximately 2.12 Wh/Kg. PMID- 20355412 TI - Electrical properties in magnetic field of macroscopic carbon nanotube objects. AB - The electrical properties including zero-field resistivity, magnetoresistance and current-voltage (I-V) curves of macroscopic carbon nanotube (CNT) objects (yarns, bundles, films, and networks) have been measured. The macroscopic CNT objects exhibit semiconductor-like behaviors. Under the magnetic field applied perpendicular to the plane or axis of the Macroscopic CNT objects, a pronounced negative magnetoresistance have been observed. Due to the aligned, close-packed structure of MWNT yarn, its MR reach as high as -17% at 9 T. The I-V curves of the MWNT network exhibit a linear relationship even at low temperature, but the other samples exhibit a nonlinear relationship, indicating the effect of morphology and defects of CNTs in macroscopic CNT objects. PMID- 20355413 TI - Effect of annealing in hydrogen atmosphere on carbon nanocap formation in surface decomposition of 6H-SiC(000-1). AB - We investigated the effect of annealing in a hydrogen atmosphere on carbon nanocap formation during decomposition of a 6H-SiC(000-1) surface. It was determined that native oxides were reduced to below the detection limit of X-ray photoelectron spectroscopy after 30 min of annealing at 1200 degrees C in a hydrogen atomosphere at 10(-3) Pa. In addition, we found that the homogeneity of carbon nanocap size was improved on the SiC surface, compared with a sample annealed in ultra-high vacuum. This technique will be useful in the fabrication of homogeneous carbon nanotube layers by surface decomposition of SiC. PMID- 20355414 TI - Purification of single-walled carbon nanotubes generated in helium ambient gas atmosphere with arc-burning apparatus by utilizing mono-dispersion technique. AB - Raw soot containing single-walled carbon nanotubes (SWNTs), generated with arc burning apparatus in helium gas atmosphere, was dispersed in 1 wt% sodium cholate (SC)/D2O solution. This solution was then used for successive ultracentrifugation procedure. After ultracentrifugation, UV-VIS and Raman spectra of the supernatant of the solution were investigated. The obtained spectra demonstrate that SWNTs generated with arc-burning method can be well mono-dispersed in surfactant solution, even though large amount of carbonaceous impurities were also included in the raw soot. This finding indicates that mono-dispersion technique can also be applied as the purification procedure for the raw soot including SWNTs of poor quality. Also, it was found that, although the yield of empty fullerenes (as byproduct) decreases as the helium gas pressure increases, that of SWNTs still increases, and shows a maximum at higher pressure. The diameter distribution of semi-conductive SWNTs included in the soot was compared with that generated in nitrogen atmosphere, based on the experimental results obtained by utilizing fluorescence mapping technique to mono-dispersed solutions. PMID- 20355415 TI - Carbon nanocubes and nanobricks from pyrolysis of rice. AB - Carbon nanocubes and nanobricks were synthesized by pyrolyzing rice powder at 600 degrees C under nitrogen atmosphere. Purification with concentrated nitric acid introduced approximately 0.1 mol/g of carboxylic acid groups as found by acid base titrimetric analysis. XRD pattern showed the 0.15 mol/g basic graphitic structure of these nano carbon materials. Their SEM and TEM images revealed cube or brick shaped nano crystals. These nanocrystals are further characterized by FT IR, Raman, and EDAX analysis. High density wrapping of carboxylated acid groups introduces surface passivation of these nano carbon cubes and nano carbon bricks exhibiting photoluminescence. Solid state electronic spectrum showed several bands in the ultraviolet and visible region and excitation at 336 and 474 nm generates photoluminescence respectively in the ultraviolet and visible region. PMID- 20355416 TI - Investigation of catalytic properties of Al2O3 particles in the growth of single walled carbon nanotubes. AB - We systematically investigate the catalytic properties of Al2O3 particles in the growth of carbon nanotubes (CNTs) in chemical vapor deposition (CVD). Compared with the conventional metal catalysts, the particle size of Al2O3 catalyst has no influence on the number of nanotube walls because only single-walled carbon nanotubes (SWCNTs) are produced. Interestingly, one large Al2O3 particle can usually nucleate several SWCNTs. However, statistical analysis reveals that the average growth rate of SWCNTs from Al2O3 catalyst is about 200 nm/min, which is much lower than that of CNTs grown from Fe catalyst under the same conditions. Additionally, a low gas pressure is found to be important for the growth of SWCNTs from Al2O3 catalyst. These results reflect that Al2O3 catalyst has different catalytic properties from the conventional metal catalysts, which will be helpful for the elucidation of the nanotube growth mechanism. PMID- 20355417 TI - Optical study on electronic transport properties of single-walled carbon nanotubes at high temperature. AB - The transport properties of single-walled carbon nanotubes (SWNTs) above room temperature are studied in this work. The infrared optical properties of SWNTs were investigated to clarify their conduction mechanism at high temperature. We present reflectivity spectra of SWNT mats in the infrared region between 0.08 eV and 0.8 eV under Ar gas flow at temperatures between 330 K and 840 K. These spectra have the typical appearance of the metallic reflectivity. Examination within the framework of the Drude-Lorentz model was performed to work out the electric resistivity for each reflectivity spectrum. It was found that the resistivity of SWNTs increases superlinearly with increasing the temperature from 330 K to 690 K, which can be explained by the quasi-1D metallic term model very well. However, the resistivity at higher temperatures than 690 K exhibited the tendency of saturation and deviated from the quasi-1D metallic term model. This behavior could be attributed to the thermal excitation of free carriers in the semiconducting SWNTs included in the mats. PMID- 20355418 TI - Current and arc pushing force effects on the synthesis of single-walled carbon nanotubes by arc discharge. AB - The current and arc pushing force of arcing process effects on the synthesis of single-walled carbon nanotubes were investigated by a temperature-controlled arc discharging furnace with Co-Ni alloy powder as catalyst at 600 degrees C. By experimental investigations, the optimal parameters of the process were obtained. The appropriate conditions included the current and arc pushing force of arcing process was 100 A and 80 A respectively, the buffer gas was helium and the gas pressure was kept at 500 torr. The experimental results indicated that the cooperative function of current and arc pushing force of arcing process played an important role in the production rate and purity of single-walled carbon nanotubes. The uniform diameter of single-walled carbon nanotubes was about 1.27 nm and the production rate was about 7 g/h and the purity was around 70%. PMID- 20355419 TI - Surface smoothness effect for the direct growth of carbon nanotubes on bulk FeCrAl metal substrates. AB - We investigate effects of surface smoothness and surface chemistry on the nature of multi-walled CNTs (MWCNTs) grown directly on FeCrAl substrates. A single sample was grown that contained a gradation in surface morphologies ranging from 2.9 nm to 30.2 nm RMS. The MWCNTs were grown using ethylene and H2 gases. Characterization was done using atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger elemental surface analysis. In smooth regions, MWCNTs demonstrated high-density vertical aligned growths; however, patches of approximately 10-20 microm where poor MWCNT growth occurred. In contrast, rough regions of the surface exhibited a continuous blanket layer of MWCNTs, albeit growth was spaghetti-like throughout this layer. The variation in nature of MWCNT growths was directly dependent on the surface roughness, which can affect surface growth chemistry of MWCNTs. Auger elemental analysis determined carbon was observed everywhere on the surface, but carbon was strongest over the smooth regions of high density growth; while relatively less carbon was detected over the patches with poor MWCNT growth, as well as over the blanket layer of the rough region. Oxygen was also measured, which was detected both within the patches of poor MWCNT growth in the smooth regions and over the blanket layer of the rough region. However, measurements of Cr and Al were exhibiting mixed trends: Cr was detected more strongly than Al over the rough region; whereas the opposite was observed in the patches of poor MWCNT growth in the smooth region. The surface smoothness affects the surface chemistry involving the nature of MWCNT growth and may also affect the surface chemistry involving the metal substrate itself; therefore, comparisons on the nature of MWCNT growths must also take careful consideration of the surface smoothness. PMID- 20355420 TI - Studies on surface functionalized single wall carbon nanotube for electrochemical double layer capacitor application. AB - Surface functionalization of single wall carbon nanotubes (SWCNTs) is carried out by chemical and electrochemical oxidation in aqueous medium. Treatment of SWCNT in acid mixtures results oxygenated surface with mainly micro porous texture which shows a pseudocapacitance of 209 Fg(-1) in 1 M H2SO4 solution at a current rate of 50 mAg(-1). The SWCNT surface become slightly non-polar when treated with fuming HNO3 even in the presence of oxygenated species. Under a current rate of 50 mAg(-1), a maximum capacitance of 202 Fg(-1) is observed in 1 M Et3MeNBF4 in polycarbonate due to presence of mesopores. Electrochemical oxidation in KNO2 functionalizes the SWCNT surface with NO2 species which shows intermediate pseudocapacitance facilitating probably organization of only smaller ions along the walls of mesopores of SWCNT. The mixed acid treated SWCNTs exhibit sensibly larger capacitance of 160 Fg(-1) even at higher current rate of 5000 mAg(-1). PMID- 20355421 TI - Low-temperature synthesis of single-walled carbon nanotubes by alcohol gas source growth in high vacuum. AB - Carbon nanotube (CNT) growth was carried out on SiO2/Si substrates with a Co catalyst using an alcohol gas source method in an ultra-high vacuum chamber. The resulting CNTs were characterized by scanning electron microscopy (SEM), Raman spectroscopy and transmission electron microscopy (TEM). Reducing the ethanol pressure decreased the optimum growth temperature for maximum yield, enabling single-walled carbon nanotube (SWNT) growth at 400 degrees C. By employing an Al2Ox buffer layer, SWNT yield increased several times, even at 400 degrees C. Under TEM observation, the Co particle size on the Al2Ox layers did not show a significant dependence on the growth temperature between 400 and 700 degrees C. Raman and TEM results confirmed activation of Co particles with larger diameter (>1 nm) by the Al2Ox buffer layer. PMID- 20355422 TI - New strategies for the enrichment of metallic single-walled carbon nanotubes. AB - Enrichment of metallic single-walled carbon nanotubes (SWNTs) has been accomplished by several means, including new extraction and synthetic procedures and by interaction with metal nanoparticles as well as electron donor molecules. In the presence of Fe(CO)5, the arc discharge method yields nearly pure metallic nanotubes. Fluorous chemistry involving the preferential diazotization of metallic SWNTs offers a good procedure of obtaining the pure metallic species. Interaction of gold or platinum nanoparticles as well as of electron-donor molecules such as aniline and tetrathiafulvalene (TTF) transform semiconducting SWNTs into metallic ones. Raman and electronic spectroscopies provide ideal means to monitor enrichment of metallic SWNTs. PMID- 20355423 TI - Synthesis, characterisation and applications of coiled carbon nanotubes. AB - Coiled carbon nanotubes are helical carbon structures formed when heptagonal and pentagonal rings are inserted into the hexagonal backbone of a 'straight' nanotube. Coiled carbon nanotubes have been reported with both regular and irregular helical structures. In this work the structure, growth mechanism(s), synthesis, properties and potential applications of coiled carbon nanotubes are reviewed. Published data suggests that coiled carbon nanotube synthesis occurs due to nonuniform extrusion of carbon from a catalyst surface. To date, coiled carbon nanotubes have been synthesised using catalyst modification techniques including: (i) the addition of S or P containing compounds during synthesis; (ii) the use of binary or ternary metal catalysts; (iii) the use of microwaves to create a local temperature gradient around individual catalyst particles and; (iv) the use of pH control during catalyst preparation. In most instances coiled carbon nanotubes are produced as a by-product; high yield and/or large-scale synthesis of coiled carbon nanotubes remains problematic. The qualitative analysis of coiled carbon nanotubes is currently hindered by the absence of specific characterisation data in the literature, e.g., oxidation profiles measured by thermogravimetric analysis and Raman spectra of pure coiled carbon nanotube samples. PMID- 20355424 TI - TiO2 rutile nanorod arrays grown on FTO substrate using amino acid at a low temperature. AB - Vertically aligned single-crystalline TiO2 rutile nanorod arrays were synthesized on FTO transparent conductive substrates, via the hydrolysis of TiCl4 under the co-existence of amino acid catalysts. Using TiO2 seed nanocrystals (prepared from Ti(IV) ethoxide, calcined at 450 degrees C for 1 h), TiO, rutile nanorod arrays grew at a relatively mild temperature of 95 degrees C for 2 days. The growth speed and morphology of nanorod array were controllable by changing the type and concentration of amino acid. XRD analysis revealed that the TiO2 nanorod arrays were composed of highly crystalline rutile phase even without calcination. Preliminary dye-sensitized solar cell performance was also reported. PMID- 20355425 TI - Fabrication and temperature-dependent photoluminescence of silicon-silicon oxide core-shell nanoparticle thin film. AB - A novel Si nanocrystals embedded SiO2 thin film has been fabricated by the synthesis of Si-SiO2 core-shell (Si@SiO2) nanoparticles via the surface SiO2 coating of Si nanocrystals and the followed drop-coating on a silicon wafer. The resultant Si@SiO2 nanoparticles had a mean diameter of 30.43 +/- 2.63 nm and a mean shell thickness of 13.16 nm. They exhibited a stronger peak around 360 nm and a weaker green-yellow emission around 530 nm. The 360 nm peak could be attributed to the electron-hole recombination in the Si cores and that via the oxide-related defects originally present on the surface of oxide-passivated Si cores, while the green-yellow emission might be attributed to the transfer of the electron-hole pairs generated in the Si cores across the core-shell interface and the followed recombination in the SiO2 shells. The resultant Si@SiO2 nanoparticle thin film had a mean grain size of about 100 nm. It showed not only blue emission and green-yellow emission but also red emission which might be due to the transfer of the electron-hole pairs generated in the Si cores across the core shell interface and the followed recombination via the Si==O double bonds at the particle surface. Because blue emission was significant relatively, both the Si@SiO2 nanoparticles and Si@SiO2 nanoparticle thin film still exhibited bright blue fluorescence under UV excitation. In addition, by investigating the temperature dependence of photoluminescence in the temperature range of 77 to 297 K, the nature of photoluminescence from the Si@SiO2 nanoparticle thin film was also clarified. PMID- 20355426 TI - Room temperature ferromagnetism in Ce(1-x)Fe(x)O(2-delta) (x = 0.0, 0.05, 0.10, 0.15 and 0.20) nanoparticles synthesised by combustion method. AB - Nanocrystalline Ce(1-x)Fe(x)O(2-delta) particles with different Fe concentrations (x = 0.0, 0.05, 0.10, 0.15, and 0.20) have been prepared by a gel-combustion method. X-ray diffraction data revealed the formation of an impurity free Ce(1 x)Fe(x)O(2-delta) products up to x = 0.15. This observation is further confirmed from the detailed studies conducted on 10 at.% Fe doped CeO2 using High Resolution Transmission Electron Microscopy (HRTEM) imaging, Selected-Area Electron Diffraction (SAED) and Raman spectroscopy. DC magnetization studies as a function of field and temperature indicate that they are ferromagnetic with Curie temperature (Tc) well above room temperature. PMID- 20355427 TI - Preparation and characterization of nanoaggregates self-assembled by lithocholic acid and N-trimethyl modified chitosan derivatives. AB - A novel kind of chitosan derivatives (CS-LA-TM) were synthesized by grafting hydrophobic molecules of lithocholic acid (LA) and quaternization. CS-LA-TM and micelle-like self-aggregates were characterized by FTIR, 1H NMR, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). The critical micelles concentration (CMC) ranging from 0.009 mg/mL to 0.030 mg/mL decreased with increasing of the degree of substitution (DS) of LA, pH of medium but with decreasing of the degree of quaternization (DQ) of amino groups. The TEM images demonstrated that spherical CS-LA-TM nanoaggregates with uniform size were formed by self-assembly. The sizes (100-200 nm) of CS-LAs-TMs nanoaggregates increased with increasing of DS, DQ, and can be easily controlled by pH of medium, which may confer the nanoaggregates potential as delivery systems for anticancer drugs, or DNA and siRNA. PMID- 20355428 TI - Uptake of functionalized mesoporous silica nanoparticles by human cancer cells. AB - Mesoporous silica nanoparticles (MSN) were functionalised by aminofluorescein (AMF) with diethylenetriaminepentaacetic acid spacer molecules which provide free carboxylic groups for binding cell-specific ligands such as folate. AMF allowed the exploration of cellular uptake by HeLa cells using confocal microscopy and flow cytometry. The functionalized nanoparticles (MSN-AMF) penetrated efficiently into HeLa cell cytoplasm through a clathrin dependent endocytosis mechanism. The number of endocytosed MSN-AMF was enhanced when using folate as a targeting molecule. Uptake kinetics revealed that most of MSN-AMF were internalized within 4 h of incubation. Moreover, we found that MSN-AMF were capable of escaping the acidic endolysosomal vesicles of HeLa cells. Cytotoxicity studies suggested that these nanoparticles are non-toxic to HeLa cells up to a dose level of 50 microg/ml. PMID- 20355429 TI - Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system. AB - The practical application of genistein as a low toxicity chemotherapeutic drug is hindered by many of its in vivo properties. To overcome these obstacles, a new multifunctional drug delivery system is developed, which is based on covalently attaching genistein onto Fe3O4 nanoparticles coated by cross-linked carboxymethylated chitosan (CMCH). The structure of the Fe3O4-CMCH-genistein nano conjugate was confirmed by transmission electron micrographs (TEM), X-ray diffraction (XRD) and Fourier-transfer infrared (FT-IR) spectroscopy. The nano conjugate shows good water solubility and superparamagnetic properties with a saturation magnetization of 55.1 emu/g. The effects of free genistein and FeO4 CMCH-genistein nano-conjugate on the proliferation and apoptosis of gastric cancer cell line SGC-7901 were investigated by MTT assay and flow cytometry (FACS). MTT results indicate that the Fe3O4-CMCH-genistein nano-conjugate exhibits a significantly enhanced inhibition effect to the SGC-7901 cancer cells than the free genistein. FACS data suggests that the inhibition on cell proliferation of the nano-conjugate is related with an induced apoptosis process. This drug delivery system is promising for future multifunctional chemotherapeutic application that combines drug release and magnetic hyperthermia therapy. PMID- 20355430 TI - Energetics of Stone-Wales defects in 4 A carbon nanotubes. AB - Density functional calculations have been performed to study the formation of Stone-Wales defects in 4 A single-wall carbon nanotubes, which were firstly synthesized inside the AFI zeolite template. The minimum energy paths from perfect tubes to defect-containing ones are calculated by the nudged elastic band method. It is found that the C--C bonds "along" the tube axis are more likely to be rotated than those bonds "around" the circumference. There is a marked chirality dependence of the formation barriers, which are found to be lower than that of graphite. Our results may raise a question on the origin of superconductivity observed in these 4 A tubes. PMID- 20355431 TI - Structural and cathodoluminescence of Sb-doped SnO2 nanostructures. AB - High density Sb-doped SnO2 nanobelts and beak-like nanorods were synthesized on alumina substrates using thermal evaporation. X-ray diffraction (XRD) pattern shows that both the nanobelts and beak-like nanorods are single crystals with the tetragonal rutile structure. Transmission electron microscopy (TEM) images show that the nanobelts grow along the [110] direction, but the nanorods grow with an abrupt change from the [101] direction to the [301] direction. X-ray photoelectron spectroscopy (XPS) analysis shows that the Sb 3d 3/2 peak of not fully oxidized beak-like nanorods shifts from 540.5 eV to 535.4 eV, and the Sn 3d 3/2 peak also shifts from 496.3 eV to 492.8 eV. Room temperature cathodoluminescence (CL) measurements show that both the nanobelts and beak-like nanorods exhibit blue and orange emissions that are related to the interstitial defects and oxygen deficiencies. The comparative study of CL measurements between nanobelts and beak-like nanorods demonstrate that the optical properties can be modified by altering the oxygen deficiencies. PMID- 20355432 TI - Reducing ability and mechanism for polyvinylpyrrolidone (PVP) in silver nanoparticles synthesis. AB - Recently, it has been found that polyvinylpyrrolidone (PVP), a popular stabilizer in nanoparticles syntheses, possesses reducing ability for Ag+. Previous explanations of the reduction are, however, thought to be plausible. Based on detailed characterizations including UV-Vis, FTIR-ATR and XPS, we uncover the existence of Ag+ -O interaction, and demonstrate that the Ag+ -PVP complex is first formed via the coordination between Ag+ and O in the carbonyl group, which facilitates electron exchange between Ag+ and adjacent N atom on the pyrrolidone ring. The N atoms with lone pair electrons serve as an electron donator, leading reduction of Ag- to form PVP-capped Ag nanoparticles ultimately. PMID- 20355433 TI - Controllable synthesis and magnetism of iron oxides nanorings. AB - Hematite (alpha-Fe2O3) nanorings were prepared via a facile hydrothermal route without using any template. The products were characterized by X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). On the basis of these characterizations and condition experiments, an "oriented dissolution and recrystallization" mechanism under the effect of H2PO4- ions was proposed to explain the formation process of nanoring structure. Magnetite (Fe3O4) nanorings were obtained by reducing alpha-Fe2O3 nanorings, and then maghemite (gamma-Fe2O3) nanorings were obtained by reoxidizing Fe3O4 nanorings. The magnetic properties of these nanorings were investigated, and it was found that these nanorings have higher coercivity and lower saturation magnetization than many other nanostructures of iron oxides. The adsorbed phosphate on the surface and the nanoring morphology might be responsible for this phenomenon. Furthermore, it is interesting to find that the coercivity of the nanorings increased with the increase of d(in)/d(out) (d(in) and d(out) are the inner and outer diameters of the rings, respectively), and a rapid increase was observed at the value of d(in)/d(out) around 0.5. PMID- 20355434 TI - Field electron emission of ZnO nanowire pyramidal bundle arrays. AB - A facile hydrothermal method was adopted to in situ grow ZnO nanowire pyramidal bundle arrays on zinc substrates at low growth temperature without the assistance of catalysts and templates. The bundle arrays were shown to form by sticking of nanowires at their tips. Field electron emission characterization of nanowires bundle arrays revealed a very low turn-on electric field of about 2.3 V/microm and a threshold electric field (corresponding to the field electron emission current density of 10 mA/cm2) of 6.8 V/microm, which are comparable to those observed in carbon nanotube arrays. The bundle arrays also show pronounced long term field electron emission stability at a high current density. In addition, the formation mechanism of the pyramidal bundled arrays and the origin of the peculiar field electron emission properties were discussed. PMID- 20355435 TI - High dielectric loss in graphite-coated Ti nanocapsules. AB - Graphite-coated Ti nanocapsules, with Ti nanoparticles as core and onion-like graphite layers as shell, have been prepared by a modified arc-discharge method in ethanol atmosphere, and characterized by means of X-ray diffraction, transmission electron microscopy and Raman spectroscopy. The dielectric properties of the graphite-coated Ti nanocapsules have been investigated in the 2 18 GHz range. An equivalent circuit model was used to interpret the non-linear dielectric resonance behavior of the graphite-coated Ti nanocapsules. The high dielectric loss is mainly attributed to conductance loss and dipole-relaxation loss in the graphite-coated Ti nanocapsules. The graphite-coated Ti nanocapsules exhibit promising properties for application as a new type of shield or absorbent of electromagnetic waves. PMID- 20355436 TI - The synthesis and optical properties of ZnO nanocombs. AB - The ZnO nanocombs were synthesized by chemical vapor deposition method, which the uniform and dense nanotips were along one side of the comb ribbon. The growth mechanism was described as free catalyst self-assembled and vapor-solid model. The optical properties related with the surface states were investigated by Raman and PL spectra. The large redshift of 1LO phonon peak was attributed to the surface and interface states. The normalized PL spectra showed that the deep level emission decreased for the sample to be annealed in O2 ambient at 500 degrees C. On the contrary, the deep-level emission increased while for the annealed sample in O2 ambient at 600 degrees C. The deep-level emission was attributed to the transition from the shallow donor to the deep acceptor. The XPS analysis showed the existence of oxygen rich and Zn deficient in the ZnO nanocombs annealed at 600 degrees C. The abnormal temperature dependence of integrated PL intensity was attributed to the abundant surface states. PMID- 20355437 TI - Crystal defects on multi-walled carbon nanotubes by cobalt oxide. AB - This paper reports a new method to make crystal defects on the surface of multi walled carbon nanotubes (MWCNTs) using the cobalt oxide as the oxidant for breaking carbon surface. The air oxidation of cobalt oxide (CoO) deposited on MWCNTs created various kinds of defects on their surface. Transmission Electron Micrograph (TEM) images showed clear defects such as broken crystal lines and asymmetric wall after air oxidation. X-ray powder diffraction (XRD) data showed that CoO on MWCNTs changed into Co3O4 after air oxidation. After removing Co3O4 from MWCNTs by acid, defective MWCNTs were obtained and showed defects of a clear trace where cobalt oxide had existed. This resulted from the reaction of air oxidation of CoO and carbon reduction of Co3O4, leading to the crystallinity defect of MWCNTs. PMID- 20355438 TI - High-yield synthesis and properties of symmetrical comb-like ZnO nanostructures on aluminum foil substrate. AB - Highly-symmetrical well-crystallized comb-like ZnO nanostructures were grown in a very large-quantity on the aluminum foil via non-catalytic thermal evaporation method by using metallic zinc powder in the presence of oxygen at low temperature of 440 degrees C. Detailed morphological investigations revealed that the as grown combs are made with a ribbon-like stem and aligned nanorod/nanowire arrays attached uniformly and nicely along one side of the ribbon-like stem. The X-ray diffraction (XRD) pattern and high-resolution transmission electron microscopy (HRTEM) revealed that the as-grown nanocombs are crystalline and possessing a wurtzite hexagonal phase. The optical properties were observed by room temperature photoluminescence (PL) and Raman-scattering which exhibited good optical properties for the as-grown products. A plausible growth mechanism has also been proposed for the formation of highly symmetrical comb-like ZnO nanostructures. PMID- 20355439 TI - Hybrid vertical architecture transistor with 2,6-diphenylindenofluorene based emitter and base permeability controlled by polystyrene spheres lithography. AB - We report on vertical architecture hybrid transistor devices using p-type silicon as collector terminal and 2,6-diphenylindenofluorene as organic semiconductor in the emitter layer. Polystyrene spheres were used as shadow masks in order to control the diameter and density of the openings in the Al metallic base. Two processes of sphere deposition were used: electrospray and dip-coating. The electrospray deposition leads to a smaller density of sphere agglomerates, but for the used sphere diameter, approximately 200 nm, the transistor performance is similar for devices prepared with sphere deposition by both techniques. The so constructed permeable-base transistors show common-emitter current gain of the order of 10(2). PMID- 20355440 TI - High-aspect-ratio structure fabrication on (110)-oriented silicon surfaces using tribo-nanolithography. AB - This study investigated methods of fabricating high-aspect-ratio structures on a silicon surface using a combination of tribo-nanolithography and wet chemical etching. Tribo-nanolithography forms an amorphous phase on a single-crystal silicon surface that has an etch resistance against potassium hydroxide so that a protruding structure can be fabricated by wet chemical etching. To fabricate high aspect-ratio structures, (110)-oriented silicon was used, and the effect of machining parameters on the structure shape was investigated. The results showed that a structure with vertical side walls could be fabricated by machining along the (112) direction. The etch resistance against potassium hydroxide depended on the normal load and number of repetitions, and the width and the maximum height were functions of these conditions. The aspect ratio of the structure increased with the etch time as long as the amorphous phase was maintained. A sub micrometer-scale high-aspect-ratio structure was fabricated based on these results, demonstrating the possibility of using this simple and effective method. PMID- 20355441 TI - Inelastic Coulomb scatterings of doped armchair carbon nanotubes. AB - For doped armchair carbon nanotubes, the free electrons in the conduction bands would cause the intraband single-particle and collective excitations. Both kinds of excitations would be split into two modes because of two different Fermi momentum states (kF'S). The excited carriers might be deexcited through such Coulomb excitations. Regarding the case where the transferred momentum L = 0, the two single-particle and the lower-frequency collective excitation modes could be the efficient deexcitation channels. In the lowest bands, the decay rates of the electron states exhibit weak Fermi energy (E(F)) dependence, but the decay rates of the hole states become greater with the increase of E(F) except for the right side k(F). Concerning the states in the higher bands, the L not equal 0 excitations also take part in the deexcitation processes. Both the electron and hole states have the same decay rates except for the case where the carriers decay to the lowest states. The decay rates contrast sharply with those of undoped carbon nanotubes and two-dimensional intercalated graphenes. It is domenated by the Fermi energy, the geometric structure and the dimensionalities. The femtosecond time-resolved photoelectron, transmission and fluorescence spectroscopies could be used to verify the predicted results. PMID- 20355442 TI - Oriented gold nanoparticle-polyaniline nanorods with nanofibers of controlled density on their surface. AB - We report here the preparation of fibrous gold nanoparticles-polyaniline (PANI) nanorod composite as an extension of our previous work in nanostructured conducting polymers. We have been able to control the amount of gold particles and the density of nanofibers covering the surface of the nanorods, which are characterized by selected area electron diffraction (SAED), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The morphology of PANI products is confirmed by both scanning electron microscopy (SEM) and TEM. The effect of reaction conditions on the morphology of PANI nanostructures is also studied. The chemical and electronic structures of the PANI nanorods are determined by Fourier transform IR (FTIR) and UV-vis spectrometry. I-V curves of as-prepared PANI nanostructures measured by conductive atomic force microscopy (c-AFM) indicate negative differential resistance (NDR) behavior. PMID- 20355443 TI - A selective fluoroionophore based on BODIPY-immobilized silica nanoparticles for Cu2+ ion. AB - A new fluorescent receptor based on BODIPY-immobilized silica nanoparticles (BODIPY-SiO2), BODIPY-SiO2, was prepared. The BODIPY-SiO2 exhibits a high affinity and selectivity for Cu2+ over competing metal ions in water. Upon the addition of Cu2+, an overall emission change of 5-fold was observed. On the other hand, except Cu2+, no significant fluorescence intensity changes were observed in the experiments using other metal ions. Interestingly, the increase in fluorescence intensity upon exposure to Cu2+ was fully reversible, as the addition of strong base to the acidic solution reversed this effect. Furthermore, we found that the BODIPY-SiO2, can remove 75% of Cu2+ ion from Cu2+ solution. Thus, the BODIPY-SiO2 can be potentially useful and effective agents of separation for selective and rapid removal of Cu2+. PMID- 20355444 TI - Synthesis and field emission properties of ultra-nanocrystalline diamond fibers and helices. AB - We propose a novel template method for large scale synthesis of Ultra Nanocrystalline Diamond (UNCD) fibres and helices with lengths of thousands of microns and diameters ranging from 0.5 to 5 microm: (i) Large quantities of submicrometer- or nanometer-diameter silica (a-SiO2) nanostructures, with lengths in the order of 2 to 4 mm, were synthesized by Vapor-Liquid-Solid (VLS) method; (ii) UNCD coating of as-synthesized a-SiO2 micro- or nanonanostructures by Microwave Plasma Chemical Vapour Deposition (MPCVD) technique in hydrogen deficient condition. Electron Field Emission (EFE) of as-synthesized UNCD structures was observed with a threshold field of 3.4 V/microm. These micro- or nanostructures may find potential applications in high power electronics, vertical field-effect transistors in vacuum electronics, heat sinks in microelectronics and structural materials in Micro- and Nano-Electro-Mechanical Systems (MEMS/NEMS). The successful preparation of various types of UNCD structures suggests that this templating process can be used for a wide range of materials. PMID- 20355445 TI - Quantum chemistry study on absorption spectra, electronic and electrical properties of organic dye on anatase(001). AB - As the most reactive surface, the stoichiometric O-bridge terminated anatase(001) surface attracted considerable attentions in many application fields. The interfacial electron transfer in dye-sensitized anatase(001) plays a principal role in a variety of photoinduced reactions. In the present work, the UV-vis absorption spectrum of TiO2 bulk and different surface models were calculated by means of tight-binding quantum chemical molecular dynamics program "Colors excite" for the first time. The thickness dependence on electronic and electrical properties of anatase(001) surface was achieved. The anatase(001) surface with a thickness of 1.0 nm shows excellent electronic and electrical properties. Moreover, the most suitable binding mode (dissociative adsorption) and absorption spectra of perylene with acrylic acid (PAA) on the optimum anatase(001) were investigated. A significant red-shift was observed from the UV-vis absorption spectrum of PAA/anatase(001) system. The red-shift occurring when PAA adsorbed on anatase(001) surface suggests that PAA/anatase(001) may be potential candidate for dye-sensitized solar cell. This study also proposed an effective computational tool "Colors-excite" to study of the electronic excitation properties for both molecular and periodic systems. PMID- 20355446 TI - Crystallization behaviour of nanostructured hybrid SiO2-TiO2 gel glasses to nanocomposites. AB - The crystallization behaviour of hybrid SiO2-TiO2 nanocomposites derived from titanosiloxanes by sol-gel method has been investigated depending on the type of siloxane precursor and the pirolysis temperature. The resulting hybrid titanosiloxanes, crosslinked with trimethylsilil isocyanate (nitrogen-modified) or methyltrietoxisilane (carbon-modified), were pirolyzed in an inert atmosphere in the temperature range between 600 to 1100 degrees C in order to form C-(N)-Si O-TiO2 nanocomposites. By means of XRD, FTIR, 29Si NMR, SEM, TEM and AFM investigations have been established that the transformation of the nanostructured SiO2-TiO2 hybrid materials into nanocomposites as well as the crystalline size depend on the titanium content and the type of cross-linking agents used in the synthesizes. PMID- 20355447 TI - A complex network based simulation approach to predict the electrical properties of nanocomposites. AB - It is well known that the addition of conducting fillers to a polymeric matrix can result in a significant improvement of its electrical and mechanical properties. Although the electrical properties of heterogeneous composites have been widely investigated in the past years, the electrical properties of composites containing carbon nanotubes are not sufficiently understood. In order to explore the potential application of complex network methods to nanocomposites, we developed a computer model that employs the Graph theory to represent and study such physical systems. From the virtual models of nanotube networks dispersed in dielectric polymeric matrices and by applying the boundary element method to numerically solve an electrostatic problem, we build a weighted network. The developed model can easily be adapted to the study of a variety of issues related to electrical behavior of filled nanocomposites. In this paper we present results from simulations aimed at studying the effect of orientation of individual nanotubes and distance between pairs of nanotubes on the capacitance. The study was also extended to the effect of the alignment of the entire nanotube network on the dielectric constant and the dielectric strength of the nanocomposite. PMID- 20355448 TI - Microstructural study of assorted ZnO nanostructures: nanocombs, nanocones and microspheres. AB - We report the microstructural study of ZnO nanostructures: nanocombs, nanocones and microspheres, synthesized using a simple thermal evaporation technique. While nanocombs require the presence of a catalyst, nanocones and hollow ZnO microspheres have been synthesized on silicon substrate in absence of any catalyst or template material. ZnO hexagonal nanocones have been synthesized on Si(100) substrates by directly evaporating zinc acetate dihydrate, at a low temperature of 400 degrees C, without using any carrier gas. The possible mechanism of formation of these structures has been discussed in brief. Chemical composition analysis by energy dispersive X-ray spectroscopy shows an O rich condition of ZnO nanocones and oxygen deficient condition of nanocombs. PMID- 20355449 TI - Measuring anisotropic friction on WTe2 using atomic force microscopy in the force distance and friction modes. AB - Layered materials which can be easily cleaved have proved to be excellent samples for the study of atomic scale friction. The layered transition metal dichalcogenides have been particularly popular. These materials exhibit a number of interesting properties ranging from superconductivity to low frictional coefficients. In this paper we have investigated the tribology of the dichalcogenide-WTe2. The coefficient of friction is less than 0.040 along the Te rows and increases to over 0.045 across the rows. The frictional forces almost doubled at normal loads of 5000 nN when scanning in the [010] direction in comparison to the [100] direction. The frictional responses of the AFM probe have been monitored in the frictional force and force-versus-distance (f-d) mode. A comparison between the outcomes using the two different modes demonstrates the factors which need to be considered for accurate measurements. PMID- 20355450 TI - Optical and structural properties of an Eu implanted gallium nitride quantum dots/aluminium nitride superlattice. AB - GaN/AIN structures made of GaN quantum dots (QDs) separated by AIN spacer layers, were doped with Europium by ion implantation. Rutherford Backscattering/Channelling measurements showed that Eu is incorporated mainly on near-substitutional cation sites within the superlattice region. Only slight deterioration of the crystal quality and no intermixing of the different layers are observed after implantation and annealing. After thermal annealing, photoluminescence associated with Eu3+ ions was observed. From its behaviour under different photon energy excitation and sample temperature we concluded that the Eu-related emitting centres are located inside the GaN QDs or dispersed in the GaN and AIN buffer or spacer layers. The 624 nm PL line, associated with Eu doped GaN QDs, shows very low thermal quenching, suggesting recombination of confined carriers through rare-earth ion excitation. PMID- 20355451 TI - Development of color tunable aqueous CdS-cysteine quantum dots with improved efficiency and investigation of cytotoxicity. AB - Cysteine capped aqueous CdS quantum dots with improved luminescence and excellent colloidal-luminescence stability were developed in a simple one pot aqueous method from safer precursors at low temperatures. Investigation of size and luminescence as a function of cysteine amount, pH and temperature revealed an optimum value for all these variables to maximize the quantum yield. Cysteine:Cd ratio of 2, reaction pH of 9.5 and synthesis at room temperature-30 degrees C emerged as the best conditions for the highest QY of 19%. Yet, QY can be improved up to 55% if QDs are cleaned from excess cysteine and ions and redispersed in pH 7 medium. Size of the QDs, therefore the color of luminescence, can be tuned by the reaction temperature in this simple process. Higher temperatures provide larger particles. Cell uptake and cell viability studies in a wide range of doses and different incubation times with MCF-7 and HeLa cell lines revealed cell dependent differences. MCF-7 cells uptake more QDs but are much more viable than HeLa cells. At low doses such as 0.025 mg QD/ml all cells are viable. At 24 h incubation times MCF-7 cells demonstrate viability above 75% up to 0.15 mg QD/mI. On the other hand HeLa cells loose viability with increasing dose. PMID- 20355452 TI - Kondo-Dicke resonances in electronic transport through double quantum dots. AB - Electronic transport through a system of two quantum dots coupled to external leads is considered theoretically. The dots are assumed to be in the Kondo regime, and the infinite-U mean-field slave-boson approach is used to obtain basic transport characteristics. Density of states and electron transmission probability in the Kondo regime are considered and calculated numerically. Both quantities are shown to exhibit features that are typical of the Dicke resonance. PMID- 20355453 TI - Tribochemical reaction dynamics of molybdenum dithiocarbamate on nascent iron surface: a hybrid quantum chemical/classical molecular dynamics study. AB - Using a hybrid quantum chemical/classical molecular dynamics method, we have studied the tribochemical reaction dynamics of molybdenum dithiocarbamate (MoDTC), a commonly used friction modifier in automobile engine oils. MoDTC molecule adsorbed on rubbing nascent iron surface was situated. We firstly investigated the dynamic behavior of MoDTC molecule on the rubbing Fe(001) surface. During the friction simulation, the elongation of Mo-O bonds was observed, forming the Mo2S4 and thiocarbamic acid molecules. To unveil the detailed mechanism of this bond elongation, the electronic states of the MoDTC molecule and Fe(001) surface were computed, and the catalytic effects of Fe(001) surface to the molecule was found. We also found that extreme friction would influence the complete Mo-O bond dissociation. By using the hybrid quantum chemical/classical molecular dynamics method, we successfully simulated the tribochemical reaction dynamics of MoDTC as a friction modifier and obtained the influences of nascent iron surface and friction on its chemical reaction. PMID- 20355454 TI - Charge carriers injection/extraction at the metal-polymer interface and its influence in the capacitive microelectromechanical systems-switches actuation voltage. AB - Opposite results concerning the sign of the parasitic charge accumulated at the metal dielectric contact in RF microelectromechanical systems (MEMS) capacitive switches are found in the literature. The mechanism concerning charge injection/extraction at the metal-dielectric contact and its influence on the pull-in voltage needs to be further clarified. A model-switch, for which only one dimension is in the microns range, is used to study the behaviour of a capacitive RF MEMS switch. The aim is to analyze how the electric charge is injected/extracted into or from the dielectric material under the applied field and to obtain realistic data to understand how this parasitic charge influences the pull-in voltage Vpi and the pull-off voltage Vpo. A triangle voltage is employed to measure Vpi and Vpo, by measuring the isothermal charging/discharging currents. Our results demonstrate that Vpi is strongly dependent on the injected/extracted charge on the free surface of the dielectric. The charge injected/extracted at the bottom side of the dielectric has no influence on the actuation voltage. The charge injected/extracted on the free surface of the dielectric determines an increase of the modulus of Vpi and, eventually, the switch can fail to actuate. An estimation of the charge stored into the material was obtained (i) by measuring the charging current and the discharging current and (ii) from the value of the Vpi. The parasitic charge necessary to keep the bridge stick to the insulator is 5.3 x 10(-4) C m(-2) for our experimental conditions. The modification of the Vpi determined by the stored charge in the dielectric is analyzed. An increase of the relative dielectric permittivity by a factor of 2 produces a decrease of the actuation voltage of 10%. A variation of 30% in the elastic constant determines a variation of about 20% in the Vpi. A voltage threshold for charge injection/extraction was not observed. PMID- 20355455 TI - Magnetocaloric effect in magnetic nanoparticle systems: how to choose the best magnetic material? AB - Magnetic nanoparticles with controlled magnetocaloric properties are a good candidate to lower the temperature of nanosized systems: they are easy to manipulate and to distribute into different geometries, as wires or planes. Using a Monte Carlo technique we study the entropy change and refrigerant capacity of an assembly of fine magnetic particles as a function of their anisotropy and magnetization, key-parameters of the magnetic behavior of the system. We focus our attention on the anisotropy energy/dipolar energy ratio by means of the related parameter c0 = 2K/M(S)2, where K is the anisotropy constant and M(S) is the saturation magnetization of the nanoparticles. Making to vary the value of co parameter by choosing different K-M(S) combinations, allows us to discuss how the magnetocaloric response of an assembly of magnetic nanoparticles may be tuned by an appropriate choice of the magnetic material composition. PMID- 20355456 TI - Effect of TiO, nanoparticles on the interface in the PET-rubber composites. AB - Usually, ceramic powders (SiO2, ZnO) are used as fillers for enhancing rubber mechanical strength. Poly-ethylene terephthalate (PET)-rubber nanocomposites were prepared by compression molding using titanium oxide (TiO2) nanoparticles as low content fillers (<2% wt). The interface properties of PET-rubber nanocomposites were studied before and after keeping the samples under UV-radiation for a week. UV-radiation has interesting potential for the photochemical modification of polymers and TiO2. The influence of UV radiation on the properties of the interface polymer-TiO2 nanoparticles was evaluated. The impact of nanoparticle aggregates on the nanometer to micrometer organization of PET-rubber composites was studied with Atomic Force Microscopy (AFM). The interface properties were explained by measuring the contact angles and surface tensions. The interactions between components of nanocomposites were investigated with Fourier Transform Infrared (FTIR) and the effects of TiO2 nanoparticle on the interfaces and composites crystalline structure were evaluated by X-ray diffraction (XRD). The results proved that the TiO2 nanoparticles, in different weight percentages, did not alter the nanocomposites crystallinity or the average crystallites size, but improve the interface properties. PMID- 20355457 TI - Coupling between plasmonic resonances in nanoparticles and porphyrins molecules. AB - A driving force for the growing interest in nanoassemblies is the use of nanoparticles linked to organic molecules. The goal of our research is to investigate the coupling of gold and silver nanoparticles (GNP and AgNP) with porphyrins molecules. We prepared water-soluble GNP and AgNP by reducing the noble metal complex salt with sodium citrate. The exchange of the initial ligand (citrate ions) with porphyrins formed hybrid nanostructures and change the electronic properties of GNP and AgNP. We highlighted the importance of the pH value to obtain the coupling of nanoparticles and porphyrins. We have shown that the absorption spectra of AgNP have a strong overlap with that of porphyrins. The effect of dye molecules on the plasmon properties of nanoparticles was demonstrated by UV-Vis, fluorescence and electrochemical spectroscopy (OTTLE cell). These new hybrid materials will be helpful for the design of light harvesting cells and sensors. PMID- 20355458 TI - Magnetic studies of ferrofluid-modified microbial cells. AB - Microbial cells (Kluyveromyces fragilis and Chlorella vulgaris) efficiently interacted with maghemite nanoparticles stabilized as low-pH ionic magnetic fluid, leading to the formation of magnetically labeled cells. This simple procedure allows to use the prepared materials as new cheap and easy to get magnetic affinity adsorbents to the removal of water-soluble dyes from polluted water sources using magnetic separation techniques. Magnetically modified cells were investigated by means of electron spin resonance spectroscopy and conventional magnetic methods over the temperature range 4-300 K. The magnetic behavior of these materials was dominated by the superparamagnetic relaxation of isolated single domain maghemite particles although a little amount of agglomerates was also present on the cell surface. However, these agglomerates were sufficiently small to show at static conditions the superparamagnetic behavior at room temperature. Therefore, the ferrofluid-modified microbial cells represent new interesting magnetic affinity adsorbents which could be applied for large-scale magnetic separation processes. PMID- 20355459 TI - A molecular simulation study of propane and propylene adsorption onto single walled carbon nanotube bundles. AB - We have carried out configurational-bias Grand Canonical Monte Carlo simulations of propane and propylene adsorption onto homogeneous bundles of single-walled carbon nanotubes, at ambient temperature (T = 298.15 K) and over a pressure range of 0.1 bar < or = p < 10.4 bar. The distinct contributions from external sites (grooves and external surface) and endohedral volume (inter- and intra-tubular) are individually addressed for bundles with nanotube diameters (D) within the range 11.0 A < D < or = 18.1 A. The different contributions from the various adsorption sites are interpreted from a molecular perspective, which takes into account both the skeletal geometry of the bundle and individual tube diameter. The resulting microscopic picture is then related to a macroscopic measurable isotherm by modeling the nanotube bundles, as a function of a characteristic hydraulic diameter (Dh) over the range 100 A < or = Dh < or = 310 A. A previously unobserved anisotropic behavior of the adsorption isotherm for the peripheral surface of the bundles as a function of hydraulic diameter is reported. PMID- 20355460 TI - Role of trimethylboron to silane ratio on the properties of p-type nanocrystalline silicon thin film deposited by radio frequency plasma enhanced chemical vapour deposition. AB - Trimethylboron (TMB) has been receiving attention as a valid alternative to diborane and methane mixtures for the deposition of p-type silicon films for applications in optoelectronic devices such as solar cells. In this paper we report on p-type hydrogenated nanocrystalline silicon carbide (nc-Si:C:H) films produced by standard 13.56 MHz plasma enhanced chemical vapour deposition technique, using TMB as gas source, under high hydrogen dilution (98%) and using high deposition pressures (3 Torr). The films obtained were characterized by spectroscopic ellipsometry (SE), Raman spectroscopy (RS), and electrical measurements to determine their optical, structural and electrical properties. We achieved conductivities as high as 8.3 (omega cm)(-1), one of the highest values of conductivity published to date using TMB with standard rf-PECVD. Spectroscopic ellipsometry modeling revealed that the films growth mechanism proceeds through a sub-surface layer mechanism that leads to the formation of nanocrystalline silicon. PMID- 20355461 TI - Effects of bias voltage on diamond like carbon coatings deposited using titanium isopropoxide (TIPOT) and acetylene/argon mixtures onto various substrate materials. AB - RF-PECVD was used to prepare amorphous of carbon (DLC) onto stainless steel 316 and glass substrates. The substrates were negatively biased at between 100 V to 400 V. Thin films of DLC have been deposited using C2H2 and titanium isopropoxide (TIPOT). Argon was used to generate the plasma in the PECVD system chamber. DEKTAK 8 surface stylus profilometer was used to measure the film thickness and the deposition rate was calculated. Micro Raman spectroscopy was employed to determine the chemical structure and bonding present in the films. Composition analysis of the samples was carried out using VGTOF SIMS (IX23LS) instrument. In addition, X-ray photoelectron spectroscopy (XPS) was used to analyze the composition and chemical state of the films. The wettability of the films was examined using the optical contact angle meter (CAM200) system. Two types of liquids with different polarities were used to study changes in the surface energy. The as-grown films were in the thickness range of 200-400 nm. Raman spectroscopy results showed that the I(D)/I(G) ratio decreased when the bias voltage on the stainless steel substrates was increased. This indicates an increase in the graphitic nature of the film deposited. In contrast, on the glass substrates the I(D)/I(G) ratio increased when the bias voltage was increased indicates a greater degree of diamond like character. Chemical composition determined using XPS showed the presence of carbon and oxygen in both samples on glass and stainless steel substrates. Both coatings the contact angle of the films decreased except for 400 V which showed a slight increase. The oxygen is thought to play an important role on the polar component of a-C. PMID- 20355462 TI - Closed field unbalanced magnetron sputtering ion plating of Ni/Al thin films: influence of the magnetron power. AB - In this study NiAl thin films have been deposited using closed field unbalanced magnetron sputtering Ion plating (CFUBMSIP). The influence of magnetron power has been investigated using dense and humongous NiAl compound targets onto stainless steel and glass substrates. Potential applications include tribological, electronic media and bond coatings in thermal barrier coatings system. Several techniques has been used to characterise the films including surface stylus profilometry, energy dispersive spectroscopy (EDAX), X-Ray diffraction (XRD) Composition analysis of the samples was carried out using VGTOF SIMS (IX23LS) and Atomic force microscopy (AFM). Scratch tester (CSM) combined with acoustic emission singles during loading in order to compare the coating adhesion. The acoustic emission signals emitted during the indentation process were used to determine the critical load, under which the film begins to crack and/or break off the substrate. The average thickness of the films was approximately 1 um. EDAX results of NiAl thin films coating with various magnetron power exhibited the near equal atomic% Ni:Al. The best result being obtained using 300 W and 400 W DC power for Ni and Al targets respectively. XRD revealed the presence of beta NiAl phase for all the films coatings. AFM analysis of the films deposited on glass substrates exhibited quite a smooth surface with surface roughness values in the nanometre range. CSM results indicate that best adhesion was achieved at 300 W for Ni, and 400 W for Al targets compared to sample other power values. SIMS depth profile showed a uniform distribution of the Ni and Al component from the surface of the film to the interface. PMID- 20355463 TI - Electron-phonon coupling assisted emission in single magnetic La0.67Ca0.33MnO3 domains of thin nanoplates. AB - A chemical method with small polymer templates is explored to obtain single magnetic domain La0.67Ca0.33MnO3 particles of thin nanoplates (25-35 nm thickness). The sample is light-emitting (480-800 nm) in multiple bands with two prominent bandgroups in the 570 nm green and 762 nm red emissions. The green emission consists of four bands 555.1, 565.7, 573.4, and 584.7 nm in the O2- -2p- > Mn3+ / Mn4+ -3d interband electronic transitions. Two excited-electronic levels G, (565.7 nm) and G2 (555.1 nm), which are exchange coupled via a phonon level v2* (678 cm(-1)), exhibit the four bands in the transitions to the ground state G0 and a phonon level v1 (575 cm(-1)). The bands v1 and v2 are well-resolved in the IR spectrum. A similar phonon assisted Mn3+ --> Mn4+ charge transfer transition results in the red emission. Both the green and red bandgroups appear in a common excitation over 350-450 nm from a xenon source. Evidently, as proposed with a model energy level diagram, the electron-phonon coupling governs a multiple light-emission in this example of the single domain particles. Otherwise, such specific ceramics of half-metallic ferromagnets hardly allows a light-emission at room temperature. PMID- 20355464 TI - Modelling the effect of contact formation on electron transfer in single-molecule device. AB - The electric properties of single-molecule devices are very sensitive to details of contact formation between the molecule and the metallic electrodes. However the factors that control the electron transfer through the molecule in these devices, corresponding to slightly different molecule-metal attachments, are not well understood. In this work, we used a self-consistent molecular dynamics method to study the effect of symmetric and asymmetric contact realizations on electron transfer between two metallic electrodes through a spatially symmetric conjugated molecule. Our results showed that both symmetric and asymmetric electron transfer, with respect to voltage inversion, can be obtained with the same molecule in agreement with the experiments. Besides, a central factor determining the asymmetric electron transfer through a symmetric molecule, caused by the asymmetric contact realization, is the oscillation of the entire molecule between both electrodes and its distortion. PMID- 20355465 TI - Noble metal nanocrystals at the surface of nitride semiconductors: synthesis, deposition and surface characterization. AB - Currently an extensive range of noble metal colloidal nanocrystals (NCs) can be readily produced by diverse chemical methods. These nanomaterials present novel physical properties and can be regarded as building blocks to the nanofabrication of smaller, energy efficient and faster devices. Moreover, when these NCs are deposited on the surface of luminescent semiconductors, as it is the case of GaN based heterostructures, exciton coupling with the metal plasmons may occur. In this work we report on the deposition of noble metal NC at the surface of InGaN/GaN multiple quantum wells (MQW), with efficient light emission in the visible range. We investigate the surface organization of Ag and Au NCs with sizes ranging from 5-30 nm as a function of deposition conditions. Scanning Electron Microscopy and Atomic Force Microscopy clearly showed that the metallic nanoparticles were successfully incorporated within the MQWs of the nitride semiconductors. PMID- 20355466 TI - Nanomechanical cantilever sensors as a novel tool for real-time monitoring and characterization of surface layer formation. AB - Nanomechanical cantilevers are small and thin, microfabricated silicon beams. They serve as extremely sensitive mechanical sensors, which transform processes occurring at their surface into a mechanical response. This unique signal transduction principle allows to measure surface stress occurring at the cantilever surface by monitoring the bending of the cantilever (static mode) while at the same time observing changes in the oscillation properties of the cantilever related to changes in mass load on the cantilever (dynamic mode). The suitability of nanomechanical cantilevers for chemical sensing, e.g., the extremely sensitive detection of heavy metals, and as biosensors, e.g., for DNA and protein detection, are well established. Arrays of cantilever sensors can be employed for the parallel detection of multiple molecules of interest. This publication will focus on more recent applications of cantilever sensors in surface and materials sciences using a commercially available cantilever sensor platform. Examples for the real-time monitoring of self-assembled monolayer (SAM) formation, the detection of cholesterol interaction with hydrophobic surface layers and the use of cantilever sensors to study layer-by-layer (LbL) build-up processes in real-time are presented. PMID- 20355467 TI - Infection free titanium alloys by stabile thiol based nanocoating. AB - As biomedical materials, titanium and titanium alloys (Ti-6Al-4V) are superior to many materials in terms of mechanical properties and biocompatibility. However, they are still not sufficient for prolonged clinical use because the biocompatibility of these materials must be improved. In this study, the prevention of the attachment of test microorganism on the Ti alloy surfaces by thiol (-SH) and hydroxyl (-OH) functional group containing monomer in plasma based electron beam generator was reported in order to prepare anti-fouling surfaces. The precursor, 11-mercaptoundecanoic acid is used as plasma source to create nano-film with 30-60 nm approximately. The surface chemistry and topology of uncoated and coated samples are characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Atomic Force Microscopy (AFM). Static contact angle measurements are performed to state the change of surface hydrophilicity. All coated samples are tested in-vitro environment with Staphylococcus epidermidis that is chosen as the test bacteria strain in view of its significance for the pathogenesis of medical-device-related infections. This test is repeated after certain period of times and samples are waited in dynamic fluid media in order to investigate the stability of nano-coating. Plasma polymerized 11 mercaptoundecanoic acid film (PP MUA) with 42 +/- 4 nm is found alternative, stabile and simple method to create bacterial anti-fouling surfaces. The static contact angle of the coated surface is 34 +/- 80 whereas the uncoated surface is 57 +/- 50. For the coated surface, the presence of C-OH and C==O groups in infrared spectra defining the PP MUA is achieved by the plasma polymerization. The attachment of the model microorganism on the biomaterial surface prepared by PP MUA is reduced 85.3% if compared to unmodified control surface. PMID- 20355468 TI - Influence of micro-channel shape and magnetic material on the magneto refrigeration process of integrated circuits. AB - We developed a two dimensional transient numerical model that solves the first step of heat transfer of an active magnetic regenerative refrigerator (AMR) using the heat conduction equation for an adiabatic system. For micro-refrigeration, an AMR device is constituted by a magnetic material, placed on a silicon wafer containing micro-channels where a heat exchanging fluid flows. The magnetic materials used in the simulations are the promising the Gd5Si2Ge2, La(Fe0.88Si0.22)13 and La0.66Sr0.33MnO3 compounds, because they exhibit a giant magnetocaloric effect near room temperature. We considered different initial conditions, namely different micro-channel shapes, sizes and separations, aiming to increase the performance of the micro-cooler device. The influence of the thickness of the magnetic material on refrigeration power is also studied. PMID- 20355469 TI - Density functional study of the oxidation of small neutral and charged silver clusters. AB - We have studied the energetic and structural stability of the interaction of molecular oxygen with small neutral, anionic and cationic silver clusters, Ag(n) (3 < or = n < or = < 8). The calculations have been carried out using a linear combination of atomic Gaussian-type orbitals within the density functional theory as it is implemented in the demon-ks3.5 code. The O2 molecule has been placed in different positions surrounding the cluster, in order to increase the configurational space of the structural minima. We have found that the oxidized cation and neutral clusters undergo a 2D-3D structural transition even before than the nonoxidized counterparts. Moreover, our results show that the adsorption energies on the cationic and neutral silver oxide clusters manifest an odd-even alternation pattern. Likewise, the average magnetic moment of the O2 radical in the charged and neutral silver environment tends to be greater than the charged and neutral bare diatomic oxygen molecule. PMID- 20355470 TI - Growth and characterisation of NiAl and N-doped NiAl films deposited by closed field unbalanced magnetron sputtering ion plating using elemental ni and Al targets. AB - Closed Field Unbalanced Magnetron Sputtering Ion Plating (CFUBMSIP) has been used to deposit undoped and nitrogen doped NiAI thin films onto glass and stainless steel 316 substrates. These films have potential applications in tribological, electronic media and thermal barrier coatings. The surface characteristics, composition, mechanical and structural properties have been investigated using stylus profilometry, X-ray diffraction (XRD), Energy dispersive spectroscopy (EDAX), Atomic force microscopy (AFM) and nanoindentation. The average thickness of the films was approximately 1 microm. The X-ray diffraction spectra revealed the presence of the beta NiAl phase. The EDAX results revealed that all of the undoped and nitrogen doped NiAl thin films exhibited the near equiatomic NiAl composition with the best results being achieved using 300 Watts DC power for Ni and 400 Watts DC power for Al targets respectively. AFM results of both types of films deposited on glass samples exhibited a surface roughness of less than 100 nm. The nanoindenter results for coatings on glass substrates displayed hardness and elastic modulus of 7.7 GPa and 100 GPa respectively. The hardest coatings obtained were obtained at 10% of nitrogen. PMID- 20355471 TI - Ferromagnetic behaviour of nickel contacted multiwalled carbon nanotubes. AB - A novel method for the contact of ferromagnetic nano-nickel onto multiwalled carbon nanotubes (MWCNTs) is proposed in this work. The process involves the decomposition of the precursor: nickel carbonyl-Ni(CO)4 into nickel and CO by laser chemical vapour deposition at 150-200 degrees C and the deposition of nano nickel onto MWCNTs. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), HR (High resolution) TEM, and Raman spectroscopy were employed for the detailed analysis of the nickel contacted MWCNTs. The ferro-magnetic nature of the sample was confirmed by Super-conducting Quantum Interference Device (SQUID) analysis. PMID- 20355472 TI - Hybrid layers deposited by an atmospheric pressure plasma process for corrosion protection of galvanized steel. AB - Finding alternative treatments to reproduce anticorrosion properties of chromated coatings is challenging since both physical barrier and self-healing effects are needed. Siloxane based treatments are known to be a promising way to achieve physical barrier coatings, mainly plasma polymerized hexamethyldisiloxane (ppHMDSO). In addition, it is known that cerium-based coatings can also provide corrosion protection of metals by means of self-healing effect. In this frame, innovative nanoAlCeO3/ppHMDSO layers have thus been deposited and studied. These combinations allow to afford a good physical barrier effect and active properties. Liquid siloxane and cerium-based particles mixture is atomized and introduced as precursors into a carrier gas. Gas mixture is then injected into an atmospheric pressure dielectric barrier discharge (DBD) where plasma polymerization of the siloxane precursor occurs. The influence of cerium concentration on the coating properties is investigated: coating structure and topography have been studied by scanning electron microscopy (SEM) and interferometry, and corrosion resistance of these different coatings is compared by electrochemistry techniques: polarization curves and electrochemical impedance spectroscopy (EIS). Potential self-healing property afforded by cerium in the layer was studied by associating EIS measurements and nanoscratch controlled damaging. Among the different combinations investigated, mixing of plasma polymerized HMDSO and AICeO3 nanoparticles seems to give promising results with a good physical barrier and interesting electroactive properties. Indeed, corrosion currents measured on such coatings are almost as low as those measured with the chromated film. Combination of nanoscratch damaging of layers with EIS experiments to investigate self-healing also allow to measure the active protection property of such layers. PMID- 20355473 TI - Electrical and Raman scattering studies of ZnO:P and ZnO:Sb thin films. AB - A study on the structure, electrical and optical properties of ZnO thin films produced by r.f. magnetron sputtering and implanted either with phosphorous (P) or antimony (Sb) is reported in this work. Raman spectroscopy, X-ray diffraction, optical transmittance and Hall effect measurements have been employed to characterize the samples. X-ray diffraction and Raman scattering patterns confirm that, after a 500 degrees C annealing, the doped films keep a polycrystalline nature with (002) preferred orientation. These films are very transparent and Hall effect results show that all have p-type conduction, despite doping ion and dose. The electric resistivity reaches values of 0.012 (omega cm) and 0.042 (omega cm) for the P and Sb-doped samples, respectively. PMID- 20355474 TI - Thermal effect on structure organizations in cobalt-fullerene nanocomposition. AB - Effect of deposition temperature (Ts) on structure of Co-C60 nanocomposite (NC) prepared by simultaneous deposition of cobalt and fullerene on sapphire is presented. The NC structure variations with Ts increasing from room temperature (RT) to 400 degrees C have been analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM) and Raman spectroscopy. AFM and SEM show granule-like structure of the Co-C60 film. The mixture film deposited at RT includes the hills on the surface suggesting accumulation of internal stress during phase separation. Raman spectra show 25 cm(-1) downshift of Ag(2) C60 peak suggesting -Co-C60- polymerization in C60-based matrix of the NC film. Analysis of Raman spectra has revealed existence of amorphous carbon (a-C) in the NC matrix that argues C60 decomposition. The Ts increase to 200 degrees C causes the surface hills smoothing. In parallel, downshift of the Ag(2) peak decreases to 16 cm(-1) that implies more pronounced phase separation and lower -Co-C60- polymerization efficiency. Also, amount of a-C content slightly increases. Further Ts increasing to 400 degrees C changes the NC structure dramatically. AFM shows evident enlargement of the granules. According to Raman spectra the high Ts deposition yields pronounced C60 decomposition increasing the a-C content. Features of a-C Raman peak imply nucleation of graphitic islands at the NC interfaces. Abundant decomposition of C60 in the mixture film deposited at 400 degrees C is referred to cobalt catalytic effect. PMID- 20355475 TI - Multicolour photochromic response of Ag-TiO2 nanocomposite--role of light illumination. AB - Multicolour photochromism of Ag-TiO2 nanocomposite material was found several years ago but its microscopic origin is still ambiguous. We study the initial stages of the effect of light exposure on extinction spectrum of this material prepared by photocatalytic technique. We propose a simple model to analyse the experimental data that suggests that the extinction changes are due to a pure shift of the plasmon resonance of silver nanoparticles after light exposure. The homogeneous spectral widths (100-200 meV) of plasmon resonance of individual classes of nanoparticles were found to increase with the resonance frequency. PMID- 20355476 TI - An investigation on solid state reactions in heat treated Au/Pd thin films for electrodes applications. AB - The interface between metals and oxides is particularly interesting. It has been the main topic of many research projects to illustrate that their properties are highly dependent on the structure of the interface. Poor adhesion between gold films and oxides is well known. On the basis of solid solution between the materials, the main effect of a Pd thin film as the adhesion layer between substrate and Au was investigated. Pure palladium and gold films were grown by electron beam evaporation sequentially on the SrTiO3 (001) single crystal substrates. After different annealing time (from 0.06 to 1.8 ks) at 500 degrees C, the growth sequence of the compositions between Au and Pd evolved as a results of the solid solution were investigated by means of X-ray photoelectron spectroscopy (XPS), X-ray diffraction. Meanwhile the surface morphology and the surface topography were examined respectively by scanning electron microscopy (SEM) and atomic force microscopy (AFM) observation. The effect of an intermediate Pd adhesion layer and its influence on the interfacial properties and morphology of the Au layer is investigated. PMID- 20355477 TI - Effect of alumina nanoparticles on hot strength and deformation behaviour of AI 5vol% Al2O3 nanocomposite: experimental study and modelling. AB - Hot deformation behaviour of as-extruded Al-5vol% Al2O3 nanocomposite was investigated at temperatures range 350 to 450 degrees C and initial strain rates of 5.5 x 10(-4) to 10(-1) s(-1) and compared with those of monolithic (unreinforced) aluminium. Both extruded materials exhibited work-softening during hot deformation. The results showed that with the addition of 5 vol% alumina nanoparticles with an average particle size of 35 nm, a significant increase in compressive strength of aluminium was obtained. For instance, at 350 degrees C an abrupt rise of approximately 340% in hot strength of the nanocomposite relative to monolithic aluminium was achieved. TEM investigation of microstructure of the nanocomposite after hot deformation showed formation of equiaxed grains from elongated ones indicating the occurrence of dynamic recrystallization. Considering experimental data, deformation behaviour of Al-5vol% Al2O3 nanocomposite and monolithic Al was modelled via trained artificial neural network (ANN). The results showed that ANN can predict complex flow behaviour of the nanocomposite as well as the monolithic aluminium. PMID- 20355478 TI - Morphological and magnetic properties of superparamagnetic carbon-coated Fe nanoparticles produced by arc discharge. AB - Spherical carbon coated iron particles of nanometric diameter in the 5-10 nm range have been produced by arc discharge at near-atmospheric pressure conditions (using 5-8 x 10(4) Pa of He). The particles exhibit a crystalline dense iron core with an average diameter of 7.4 +/- 2.0 nm surrounded by a sealed carbon shell, shown by transmission electron microscopy (TEM), selected-area diffraction (SAED), energy-dispersive X-ray analysis (STEM-EDX) and electron energy loss spectroscopy (EELS). The SAED, EDX and EELS results indicate a lack of traces of core oxidized phases showing an efficient protection role of the carbon shell. The magnetic properties of the nanoparticles have been investigated in the 5-300 K temperature range using a superconducting quantum interference device (SQUID). The results reveal a superparamagnetic behaviour with an average monodomain diameter of 7.6 nm of the nanoparticles. The zero field cooled and field cooled (ZFC-FC) magnetization curves show a blocking temperature (T(B)) at room temperature very suitable for biomedical applications (drug delivery, magnetic resonance imaging, hyperthermia). PMID- 20355479 TI - Microwave effects in silicon low dimensional nanostructures. AB - We review the effects of microwave irradiation on low dimensional electron systems in Silicon nanostructures. Depending on the temperature and the energy scales involved, different effects may be observed on the transition probabilities of elastic and inelastic processes. In particular two cases of 0 dimensional confinement are analyzed, i.e., the trapping of a single electron in point defects close to a two dimensional electron system, and in single donor atoms trapped in the channel of a nanoMOSFET. Microwave dependent capture and emission phenomena and photon assisted tunneling are described in such kind of systems. Consequences on the single spin resonance detection and on the spin manipulation are discussed. PMID- 20355480 TI - Photosensitizer methylene blue-semiconductor nanocrystals hybrid system for photodynamic therapy. AB - In this work we report on the development of novel hybrid material with enhanced photodynamic properties based on methylene blue and CdTe nanocrystals. Absorption spectroscopy, visible photoluminescence spectroscopy and fluorescence lifetime imaging of this system reveal efficient charge transfer between nanocrystals and the methylene blue dye. Near infra-red photoluminescence measurements provide evidence for an increased efficiency of singlet oxygen production by the methylene blue dye. In vitro studies on the growth of HepG2 and HeLa cancerous cells were also performed, they point towards an improvement in the cell kill efficiency for the methylene blue-semiconductor nanocrystals hybrid system. PMID- 20355481 TI - Crystal size and crystalline volume fraction effects on the Erbium emission of nc Si:Er grown by r.f. sputtering. AB - Erbium-doped low-dimensional Si films with different microstructures were grown by reactive magnetron sputtering on glass substrates by varying the deposition parameters. Their structure and chemical composition were studied by micro-Raman and Rutherford backscattering spectrometry, respectively. In this contribution the Erbium emission is studied as a function of nanocrystalline fraction and average crystal sizes and also as a function of the matrix chemical composition. We discuss the temperature dependence of the Er3+ emission as well as the possible explanations of the low Er active fraction. PMID- 20355482 TI - Structural and optical characterization of ZnO nanowires grown on alumina by thermal evaporation method. AB - Zinc oxide nanowires have been grown on alumina substrate by thermal evaporation of zinc nanopowder in the presence of oxygen flow. The growth was performed under ambient pressure and without the use of foreign catalyst. Scanning electron microscopy (SEM) observation showed that the as-grown sample consists of bulk ZnO crystal on the substrate surface with nanowires growing from this base. Growth mechanism of the observed morphology is suggested to be governed by the change of zinc vapour supersaturation during the growth process. X-ray diffraction (XRD) measurement was used to identify the crystalline phase of the nanowires. Optical properties of the nanowires were investigated using Raman scattering and photoluminescence (PL). The appearance of dominant, Raman active E2 (high) phonon mode in the Raman spectrum has confirmed the wurtzite hexagonal phase of the nanowires. With above bandgap excitation the low temperature PL recombination is dominated by donor bound exciton luminescence at -3.37 eV with a narrow full width at half maximum. Free exciton emission is also seen at low temperature and can be observed up to room temperature. The optical data indicates that the grown nanowires have high optical quality. PMID- 20355483 TI - Influence of deposition pressure on N-doped ZnO films by RF magnetron sputtering. AB - N-doped ZnO films were deposited on glass substrates by RF magnetron sputtering with different deposition pressures. The samples were characterized by X-ray diffraction (XRD), atomic force morphology (AFM), X-ray photoelectron spectroscopy (XPS), Hall measurements and optical spectrophotometer. The XRD patterns confirmed that the films are polycrystalline and the influence of deposition pressure on the structural properties. AFM microstructures also authenticated the change in the size and shape of the grains as a function of deposition pressure; the root mean square (RMS) roughness has reached a maximum (10.65 nm) at 1.5 x 10(-2) mbar. XPS spectra revealed the change in the chemical composition. The amount of adsorbed oxygen and nitrogen at oxide sites has reached the maximum at 9.0 x 10(-3) mbar, where the film showed p-type conductivity. The optical transmittance spectra have indicated that the absorption edge is shifted towards the shorter wavelength at higher deposition pressure. Correspondingly, the optical band gap is increased from 2.17 to 2.80 eV. The average visible transmittance in the wavelength ranging 500-800 nm has been increased from 49% to 82%. PMID- 20355484 TI - Magnetic nanocomposites fabricated via the layer-by-layer approach. AB - In this study we describe the fabrication and characterization of nanocomposites consisting of layer-by-layer assembled polyaniline, sulfonated polystyrene, and maghemite nanoparticle layers. In order to assemble the starting components via electrostatic interaction, stable magnetic fluid containing maghemite nanoparticles (d approximately = 7 nm) with either positive or negative surface charges was used as source of nanoparticles for the layer-by-layer assembly. The structure, morphology, electrical and magnetic properties of such nanocomposite films were investigated by UV-Vis spectroscopy, atomic force microscopy, electrical, and magnetic measurements. The amount of PANI, PSS and maghemite nanoparticles within the nanocomposite films increased almost linearly with the number of deposited layers. Atomic force microscopy image of typical polyaniline/maghemite nanocomposites reveal nanoparticles adsorbed all over the film surface. The as-produced nanocomposite exhibits electrical conductivity and superparamagnetism behavior at room temperature, the latter confirmed by the absence of magnetic hysteresis. PMID- 20355485 TI - Cure behavior and physical properties of epoxy resin-filled with multiwalled carbon nanotubes. AB - Different experimental procedures were investigated for incorporating Multi walled Carbon nanotubes (MWCNT) into epoxy diglycidil-ether bisphenol-A (DGEBA), cured with 4,4' diamine-dibenzyl-sulfone (DDS): (i) mechanical mixing for either 60 or 120 minutes; (ii) high energy ball milling for 30 minutes; (iii) ultrasonication for 20 minutes. The mechanical properties of the obtained samples were monitored and used in order to guide the selection of the most promising composite system. The best results were obtained by using, as method of incorporation of carbon nanotubes in the resin, sonication for 20 minutes. Moreover it was found that the presence of an accelerating agent, BF3, commonly used for the cure reaction, is ineffective in the presence of carbon nanotubes, besides leading to composites with a lower glass transition. Afterwards resins with increasing MWCNT concentration were prepared and the thermal properties analyzed, showing a slight improvement in either the glass transition or the degradation temperature. The electrical conductivity of the selected composite system is characterised by a percolation threshold (lower than 0.1%) comparable to that found for similar systems, but beyond threshold it assumes greater values. The conductivity is characterised by only a slight increase with temperature in the range 30-90 degrees C. The positive temperature coefficient can be related to a decrease of the small gaps separating the CNTs clusters. A simple power law describes the relation between the composite conductivity and CNT concentration near the percolation threshold. A dependence of all the parameters of the power law on the temperature has also been evidenced, and it should be properly considered and indicated when using such a model in describing the behaviour of composites near the percolation threshold. PMID- 20355487 TI - Undoped InOx films deposited by radio frequency plasma enhanced reactive thermal evaporation at room temperature: importance of substrate. AB - Conductive and transparent undoped thin films of indium oxide (InOx ), 120 nm average thick, were deposited by radio frequency plasma enhanced reactive thermal evaporation (rf-PERTE) of indium in the presence of oxygen at room temperature. Several substrates were used in order to study their influence on the main properties of these films: alkali free (AF) glass, fused silica, crystalline silicon and polyethylene terephthalate (PET). Surface morphology of the InOx films as a function of the substrates was observed by SEM and showed that the undoped InOx films obtained are nanostructured. For the c-Si substrate, InOx films with increased grain size are obtained, induced by the crystalline substrate. Films deposited on fused silica and AF glass substrates show a nano grainy surface with similar surface morphologies. The InOx films deposited on AF glass show the highest values of both: electrical conductivity of about 1100 (omega cm)(-1) and visible transmittance of 85%. The substrate has a greater influence on the surface morphology of the films when a polymer (PET) is used. InOx films deposited on PET show a decrease in the electrical conductivity (90 (omega cm)(-1)) and a slight decrease in the average visible transmittance (78%). PMID- 20355486 TI - Nanostructured silicon particles for medical applications. AB - Porous silicon (PS) which has different properties from the bulk material due to the quantum confinement effects is beside other physical properties (e.g., light emitting) bioactive or even bioresorbable. The aim of this paper is to optimise the experimental conditions for the fabrication of nanostructured Si particles and to find the best methods for attaching on its surface molecules of therapeutic interest. The selective porosification has been performed using (i) a dielectric/metallic masking layer micropatterned with corresponding etching windows; (ii) a controlled diffusion process leading to n-type islands into p type Si substrate. The PS particles were detached from the Si substrate by switching the electrochemical etching conditions from porosification towards the electropolishing regime. Also, similar results were obtained by fabrication of PS multilayer structures subjected to an additional ultrasonation process. Different organic molecules with antitumoral effect, such as chondroitin sulphate (a sulphated glycosaminoglycan), lactoferrin (globular protein with antimicrobial activity) and N-butyldeoxynojirimycin (an imino sugar that inhibits the growth of the CT-2A brain tumour) were covalently attached on the PS particle surface using 3-aminopropyltriethoxysilane (APTS) molecule as linker. Furthermore, to complete the administration/therapy of drugs, for microparticle targeting and imaging, Fe3O4 nanoparticles were integrated in PS matrix by co-precipitation from a solution of iron salts (Fe3+/Fe2+) in alkaline medium. Microscopic and spectroscopic analyses have been used to characterize the Si microparticles. Tumoral cells were cultivated on the nanostructured PS particles and a significant decrease of the cells density was observed on all investigated samples comparatively with the blank substrate without antitumoral molecules. PMID- 20355489 TI - On the role of tin doping in InOx thin films deposited by radio frequency-plasma enhanced reactive thermal evaporation. AB - In view of the increasing need for larger-area display devices with improved image quality it becomes increasingly important to decrease resistivity while maintaining transparency in transparent conducting oxides (TCOs). Accomplishing the goal of increased conductivity and transparency will require a deeper understanding of the relationships between the structure and the electro-optical properties of these materials. In this work we study the role of tin doping in InOx thin films. Undoped indium oxide (InOx) and indium tin oxide (ITO) thin films were deposited at room temperature by radiofrequency plasma enhanced reactive thermal evaporation (rf-PERTE), a new technique recently developed in our laboratory using as evaporation source either In rods or a 90%In:10%Sn alloy, respectively. The two most important macroscopic properties-optical transparency and electrical resistivity-seem to be independent of the tin content in these deposition conditions. Results show that the films present a visible transmittance of the order of 82%, and an electrical resistivity of about 8 x 10( 4) omega x cm. Surface morphology characterization made by atomic force microscopy (AFM) showed that homogeneity of the films deposited from a 90%In:10%Sn alloy is enhanced (a film with small and compact grains is produced) and consequently a smooth surface with reduced roughness and with similar grain size and shape is obtained. Films deposited from pure In rods evaporation source show the presence of aggregates randomly distributed above a film tissue formed of thinner grains. PMID- 20355488 TI - Synthesis of plasmonic nanocomposites for diverse applications. AB - We report the synthesis of gold and silver nanostructures embedded in different dielectric matrices by atom beam co-sputtering, a novel technique. We have synthesized gold-silicon core shell nanostructures and Au-ZnO nanocomposite with tunable surface plasmon resonance (SPR) by atom beam co-sputtering and subsequent annealing. The Au-ZnO nanocomposite shows significant enhancement in intensity of Raman modes of fullerene molecules and therefore can help in surface enhanced Raman spectroscopy investigation of organic molecules. The synthesized Ag-polymer nanocomposite thin films show excellent features of broad SPR absorption extending upto IR region and a narrow transmission of light in UV region approximately 320 nm which could be of technological interest in solar absorbers and UV light filters respectively. The Ag-silica nanocomposite thin films show their utility in glucose sensing. The gold-silica nanocomposite thin films exhibit their possible use in detection of human ovarian cancer cells in a preliminary study. The shift in SPR peak of Au nanoparticles (NPs) present at the surface of silica synthesized by thermal evaporation and annealing, after attachment of biological molecules like proteins has been studied. PMID- 20355490 TI - Role of the dipolar interaction on the macroscopic state of magnetic nanoparticle systems: a Monte Carlo study. AB - We have performed Monte Carlo simulations to treat the effect of the dipolar interaction in assemblies of superparamagnetic nanoparticles. Our simulations reproduce correctly the increase of the blocking temperature (T(B)) as the concentration increases, as observed experimentally. Interestingly, we have observed a progressive displacement of the M2 versus H/M isotherms (Arrott plots) from the origin as the concentration of nanoparticles increases. Moreover, the curvature of the isotherms at T > T(B) changes from positive to negative slope at high sample concentrations, resembling the shape of a first order phase transition. These results are surprisingly similar to that found in a conventional magnetic phase transition under the effect of a random anisotropy or a random field. PMID- 20355491 TI - Role of nitrogen additive and temperature on growth of diamond films from nanocrystalline to polycrystalline. AB - In this work, the coupled effect of nitrogen addition into CH4/H2 mixtures and surface temperature on diamond growth ranging from large grained polycrystalline to fine-grained nanocrystalline were investigated. Moreover a new growth parameter window for simultaneous growth of nanocrystalline diamond (NCD) and {100} textured large-grained diamond films was developed by using a high power high pressure 5 kW microwave plasma assisted chemical vapor deposition (MPCVD) reactor. Scanning electron microscope (SEM), Raman spectroscopy, and X-ray diffraction (XRD) are employed to characterize the morphology, crystalline quality and texture of the diamond samples. Our results can be grouped by two catalogs: First, deposition run without and with 0.24% N2 addition, while keeping all the other parameters constant, resulted in a high quality transparent large grained polycrystalline diamond film and a NCD film, respectively. This result clearly evidences nitrogen induced nanocrystallinity. Then, two different substrate surface temperatures were obtained by overlapping a small silicon slice on the top centre of a large silicon wafer of 5.08 cm in diameter in only one deposition run using 0.24% N2 addition and the same set of parameters as the previous runs. From this growth run, a NCD film of growth rate around 2.3 microm/h was obtained at low temperature, while a {100} textured large-grained diamond film of much higher growth rate about 10.4 microm/h was grown at high temperature. These results not only confirm the reproducibility of NCD by N2 addition, but also indicate that distinct growth modes were involved at different substrate temperatures with 0.24% nitrogen addition, or coupled effect of nitrogen addition and temperature on the growth of CVD diamond films happened. Finite element method (FEM) analysis was employed to simulate the temperature gradient and distribution on these two samples, and based on this simulation and other simulation results in the literature, the growth mechanism is briefly discussed. PMID- 20355492 TI - Influence of pinholes on MgO-tunnel junction barrier parameters obtained from current-voltage characteristics. AB - Magnetic tunnel junctions (MTJs) with thin barriers are already used as read sensors in recording media. However, the presence of pinholes across such few A thick barriers cannot be excluded and one needs to investigate their effect on the MTJ-transport properties. By applying large electrical currents we could change the electrical resistance of the studied MgO MTJs (due to pinhole-size variations), and study how pinholes influence the barrier parameters (thickness t and height phi) obtained by fitting current-voltage characteristics to Simmons' model. We found that, with decreasing resistance, the barrier thickness (height) decreases (increases). These results were well reproduced by a model of parallel resistances, allowing us to estimate pinhole-free barrier parameters. PMID- 20355493 TI - Study on Al-Si alloy-based nanocomposites with dispersed detonation nanodiamonds. AB - Al-Si alloy-based nanocomposites with dispersed detonation nanodiamonds are fabricated by a powder metallurgy method. Rapid-solidified Al-Si alloy powder and detonation nanodiamond of 1% by volume are mechanically mixed at 500 rpm for 4 h; the nanoadditives used above are as-synthesized and purified detonation nanodiamonds. The obtained Al-Si nanocomposite mixtures are consolidated at 773 K by vacuum-hot pressing. The microstructural observations indicate that the fabricated Al-Si nanocomposites have fine grain structures with dispersed eutectic Si particles and detonation nanodiamonds in the grains; structural changes in the dispersed nanodiamonds are not observed. The mechanical and friction properties of the fabricated Al-Si nanocomposites with dispersed detonation nanodiamonds are investigated by carrying out indentation and friction measurements. It is observed that the dispersion of detonation nanodiamonds in the Al-Si alloy matrix improves its mechanical and friction properties. In particular, the dispersion of the purified detonation nanodiamond enhances the elastic modulus of the nanocomposite to a greater extent than that of the as synthesized detonation nanodiamond with graphitic shell structure; in contrast, the use of the as-synthesized detonation nanodiamond reduces friction to a greater extent than the use of the purified detonation nanodiamond. PMID- 20355494 TI - XPS analysis by exclusion of a-carbon layer on silicon carbide nanowires by a gold catalyst-supported metal-organic chemical vapor deposition method. AB - Silicon carbide (SiC) nano-structures would be favorable for application in high temperature, high power, and high frequency nanoelectronic devices. In this study, we have deposited cubic-SiC nanowires on Au-deposited Si(001) substrates using 1,3-disilabutane as a single molecular precursor through a metal-organic chemical vapor deposition (MOCVD) method. The general deposition pressure and temperature were 3.0 x 10(-6) Torr and 1000 degrees C respectively, with the deposition carried out for 1 h. Au played an important role as a catalyst in growing the SiC nanowires. SiC nanowires were grown using a gold catalyst, with amorphous carbon surrounding the final SiC nanowire. Thus, the first step involved removal of the remaining SiO2, followed by slicing of the amorphous carbon into thin layers using a heating method. Finally, the thinly sliced amorphous carbon is perfectly removed using an Ar sputtering method. As a result, this method may provide more field emission properties for the SiC nanowires that are normally inhibited by the amorphous carbon layer. Therefore, exclusion of the amorphous carbon layer is expected to improve the overall emission properties of SiC nanowires. PMID- 20355495 TI - Effect of titanium oxide nanoparticle incorporation into nm thick coatings deposited using an atmospheric pressure plasma. AB - This study reports on the use of an atmospheric plasma technique to incorporate metal oxide nanoparticles into nm thick siloxane coatings. Titanium dioxide (TiO2) particles with diameters of 30-80 nm, were mixed with a number of different siloxanes-polydimethylsiloxane, hexamethyldisiloxane and tetraethylorthosilicate (TEOS). The TiO2/TEOS mixture was found to give the most stable suspension, possibly due to the higher surface tension of TEOS compared with the other siloxanes. TiO2/TEOS mixtures with 2 to 10% by weight of the metal oxide were prepared and were then nebulised into a helium/oxygen atmospheric plasma. Polyethylene terepthalate (PET) and silicon wafer substrates were passed through this plasma using a reel-to-reel substrate manipulation system. SEM combined with EDX was used to examine the distribution of the metal oxide particles in the resultant coatings. The TEOS coating thickness without TiO2 addition was 9 nm. The composite coating consisted of a relatively homogeneous distribution of small agglomerates of the TiO2 nanoparticles in TEOS. A linear increase in the titanium surface concentration was observed with increase in the quantity of TiO2 added into the siloxane precursor. The chemical functionality of the siloxane coating was examined using FTIR spectroscopy and no significant spectrum differences was observed with the incorporation of the different concentrations of TiO2 into the polymer. There were also no changes observed in coating surface energy with TiO2 incorporation. Coating morphology was examined using optical profilometry and surface roughness (Ra) values increased from typical values of 0.8 nm for the TEOS coating to 4.1 nm for the TiO2/TEOS coating. The adhesion of the deposited coatings was compared using fragmentation tests. These were carried out through uniaxial tensile loading. The coating cracking pattern after applied strain of 20% was not observed to change significantly with the addition of TiO2 into the siloxane. PMID- 20355496 TI - Lying-down metallic single-walled carbon nanotubes as efficient linkers for metalloprotein-based nanodevices. AB - Metalloproteins recently emerged as good candidates for signal transduction in bionanodevices, but the feasibility of such novel devices is strongly connected to the achievement of an efficient charge transport between single metalloproteins and metal electrodes. In this work, we propose the use of metallic single-walled carbon nanotubes as efficient linkers between metalloproteins and metal surfaces. By means of a conductive atomic force microscopy investigation, we compare the conduction across single yeast cytochrome c molecules covalently bound both to bare gold and to functionalized metallic single-walled carbon nanotubes lying on gold. At comparable forces applied by the microscope tip (i.e., comparable physical contact), the measured current is higher when a metallic single-walled carbon nanotubes is in between the metalloprotein and the gold surface. The analysis of the single molecule current responses by means of a non-resonant tunneling transport model suggests that the increasing in the conduction is due both to the strong electronic conjugation existing at the nanotubes/gold interface and to the participation of the nanotube electronic bands to the charge transport. PMID- 20355497 TI - The effect of the addition of carbon nanotubes in the hydrothermal synthesis and in the thermal phase stability of nanozirconia. AB - The yttria partially stabilized zirconia is a very attractive material for orthopaedic applications. It exhibits excellent biocompatibility, high fracture toughness, high strength and low wear rates. But case studies show that delayed failure can occur in vivo due to crack propagation. Carbon nanotubes could avoid the slow crack propagation and enhance the toughness of the ceramic material used for prostheses fabrication. In this work, X-ray diffraction has been used to study the influence of the addition of MWCNT on the hydrothermal synthesis of tetragonal zirconia nanoparticles and on the phase stability of the CNT nanozirconia nanocomposite with the temperature. First, the influence of the processing variables on the hydrothermal synthesis has been studied. The theoretical mathematical models that relate the percentage of tetragonal zirconia nanocrystals and the relative crystallinity with the processing variables in the range of analyzed values have been obtained. The values that give the maximum percentage and crystallinity of tetragonal phase in the studied range have been established. No significant differences were observed in the crystalline phases obtained when adding MWCNT during the synthesis. Nanozirconia partially coated MWCNT synthesized under the optimized parameters were added to commercially available nanozirconia particles and their influence in the phase stability of the zirconia with the temperature was studied by XRD. It was concluded that the addition of the carbon nanotubes delays both the monoclinic phase decomposition and the grain growth. PMID- 20355498 TI - UV emission from patterned growth of ZnO nanowires. AB - Patterned and high-density ZnO nanowires were fabricated on a large area P type silicon (100) through Vapor-Liquid-Solid approach. An aluminium mask was used for the patterned deposition of gold catalyst. ZnO nanowires grown with the aid of gold catalyst were well aligned and had dimensions of 30-80 nm diameter and 0.5-2 microm length. The perfect crystallinity and orientation [0002] of the nanowires were confirmed by high-resolution transmission electron microscopy (HR-TEM). Low temperature photoluminescence spectrum exhibits an intensive UV emission at approximately 380 nm and a weak broad green band at approximately 530 nm which is detected under an optical excitation of 325 nm wavelength of He-Cd laser. These arrays of ZnO nanowires could have myriad applications in nanolasers, optoelectronic devices and optical interconnects. PMID- 20355499 TI - From single-molecule precursors to hybrid ZnS nanostructures. AB - A series of coordination compounds containing [Zn(amine)]2+ cationic complexes and alkyldithiocarbamates (RR'dtc-), as counter anions, are reported here: [Zn(amine)x][RR'dtc]2, where amine = ethylenediamine (en), diethylenetriamine (dien), 1,2-diaminopropane (dap) and, R,R' = ethyl (Et); butyl (Bu) and methyl (Me), hexyl (Hex). Hybrid nanoplates composed of hexagonal-ZnS nanoparticles and organic components were obtained after solution phase thermolysis of such precursors in oleylamine. These hybrid materials show quantum confinement effects in their optical spectra and convert into cubic-ZnS after further thermal treatment. PMID- 20355500 TI - Polymer light emitting diode using PFT--poly(9,9'-n-dihexil-2,7 fluorenodiilvinylene-alt-2,5thiophene). AB - The development of new electroluminescence polymers for specific colour tuning in Polymer Light Emitting Devices (PLEDs) is currently one of the most important fields for organic electronics. This work reports a synthesis of a new electroluminescent polymer and the concomitant test as PLED emissive layer. The polymer, synthesised from fluorene, is poly(9,9'-n-dihexil-2,7 fluorenodiilvinylene-alt-2,5thiophene) or PFT. The luminescence shows large bands with maxima around 480 nm in absorption and 560 nm in emission. The device was made in a three layer structure, with PEDOT:PSS as hole transport layer, PFT as emissive layer and butyl-PBD as electron transport layer. The electroluminescence spectrum shows a strong band peaked at 540 nm. For an applied voltage of 12 Volt, the brightness at normal angle of viewing is near 10 cd/m2 and the luminous efficiency is of 0.01 lm/W. A discussion about carrier transport and the electroluminescence properties is made. PMID- 20355501 TI - Photoluminescent materials based on silica doped with lanthanide complexes of 4' formylbenzo-15-crown-5. AB - Photoluminescent materials were prepared by introducing lanthanide complexes of 4'-formylbenzo-15-crown-5 (C15H20O6) into a silica matrix obtained by the sol-gel method. The new lanthanide complexes [Ln(C15H20O6)(NO3)3(H2O)2] (Ln3+ = Sm3+, Eu3+ and Tb3+) were synthesized and were fully characterised using spectroscopic techniques, and elemental and thermogravimetric analysis. Photoluminescence measurements were performed for the isolated Eu3+ and Tb3+ complexes as well as for their related silica based materials. A detailed comparative analysis on the photoluminescent properties of the EU3+ complex and of its derived silica material was carried out. PMID- 20355502 TI - Small Au clusters oxidation: an ab initio study. AB - We have performed ab initio calculations in the Density Functional Theory framework on unsupported small gold clusters with size ranging from three to seven atoms. In our calculations we have introduced a single O2 molecule on different places around the cluster surface, and in both parallel and perpendicular position with respect to the cluster surface. We have found that the oxygen molecule bonds in-plane with the bidimensional Au cluster when the number of Au atoms is even, and it will be adsorbed off-plane if the number of Au atoms is odd. The latter case, despite not presenting a true chemical bonding, has great stability due to spin pairing and electrostatic interactions, and the structures will be distorted respect to the geometry of their pure Au cluster equivalents. PMID- 20355503 TI - Numerical simulation of in-vitro dispersion and deposition of nanoparticles in dry-powder-inhaler aerosols. AB - Aerosol dispersion and deposition inside an idealized mouth-throat has been numerically simulated using a stochastic Lagrangian model accounting for Brownian motion and particle-wall interaction. Delivery of nanoparticles to the lungs is extremely difficult, mainly due to their low inertia, and for this reason they are often loaded into larger carrier particles. Bearing in mind the potentialities of nanoparticles in advanced drug delivery, a set of monodisperse particles with diameters in the nanqsize range, as well as in the respirable and carrier ranges, were considered in the present simulations. Deposition patterns were obtained by tracking a total of 16,000 particles for each diameter. The results have shown that similar patterns were obtained in the mouth-throat for 400 nm particles and larger. A clear correspondence between secondary flow structures in the fluid and these deposition patterns was observed, demonstrating the role of the convective transport processes for this size range. In contrast, a much more uniform distribution of the particles adhering to the walls was noted for a size of 200 nm. It was also found that a very large amount of these particles (nearly 80%) is lost by deposition on the mouth-throat, thus recommending the use of larger carrier particles. PMID- 20355504 TI - Carbon nanotube-polymer based nanocomposite as electrode material for the detection of paraoxon. AB - Biosensor based on the inhibition of enzymes has been used for the detection of organophosphorous compounds wherein amperometic method has been employed. Carbon nanotubes (CNT) has been grown over YNi3 alloy hydrides and purified for further use. The high surface area and the acidic sites created during the purification of CNT with oxidizing acids have been exploited for the adsorption and entrapment of the enzyme acetylcholine esterase. In the present work, conducting polymer polypyrrole has been uniformly coated over the CNT surface using chemical oxidative technique. The nanocomposite was characterized by scanning electron microscopy (SEM) and High resolution transmission electron microscopy (HRTEM). In the present report high catalytic activity of CNT towards the electroxidation of thiocholine has been utilized for the detection of organophosphorous compound paraoxon. Developed biosensor uses the principal of acetylcholinesterase inhibition by nerve agent and hence reduction in oxidation current of thiocholine for the detection of paraoxon. Synthesized PPY-MWNT nanocomposite has been used for the electrode preparation over GC electrode. Due to high porosity of polymer and high electrical conductivity of CNT, a detection level of 3 nM paraoxon could be achieved. The details of fabrication of the sensor and the dependence of the sensitivity have been discussed. PMID- 20355505 TI - Time-resolved photoluminescence spectra, lifetime distributions and decay associated spectra of lanthanide's exchanged microporous-mesoporous materials. AB - Time-resolved luminescence spectra of europium in parent and silylated microporous-mesoporous materials were analyzed by using the maximum entropy method and global multi-exponential fitting, providing lifetime distributions and decay-associated spectra. Silylation was used as a method for the hydrophobization of the materials surface in order to inhibit the moisture intrusion at the lanthanide's sites. Due to the well-known sensitivity of the europium photoluminescence properties to the local environment, our approach can simplify the description of the complex structure-photoluminescence relationships in terms of the individual europium species that contribute to the total emission of the system. PMID- 20355506 TI - Field effect devices and sensors based on electrospun polymer assisted tin oxide nanoribbons. AB - Electrospinning is presented as a facile method of preparing relatively long tin oxide (SnO2) nanofibers that are robust and stable in air. Upon heat treatment, the fibers collapse into a ribbon-like structure with surfaces that are not smooth, rather, are marked with several interconnected pathways. These nanoribbons were electrically characterized in a field effect transistor configuration in vacuum, with and without ultra violet (UV) light exposure. The resultant variable resistor device exhibits n-type behavior having an on/off ratio of approximately 6000. The devices show a direct response to UV with faster response times upon exposure to longer wavelength light. In the presence of UV, the device conductance and mobility increases, reaching a value approximately 2 cm2/-s for the 364 nm UV light source, comparable to amorphous Si. PMID- 20355507 TI - Preparation and characterization of chitosan/SiO2 composite films. AB - Composite films made from chitosan, plasticizer, and incorporated silica nanoparticles were evaluated for their mechanical properties, thermal stability, water permeability, and surface characteristics. The influence of the chitosan amino group protonation upon the observed silica effects was also analyzed. Only slight differences between most of the properties of composite films and those of the biopolymer alone were observed. The lack of complete and uniform dispersion of the silica particles within the biopolymer matrix and the absence of relevant polymer-filler interactions in such composite membranes lead to a low level of interaction between the filler and the polymer, and only a reduced effect of the filler on the film properties. The silica effects worthy to mention are the decrease in Young's modulus and the increase in film elongation, and the slight influence on surface hydrophobicity and water vapour permeability, which were dependent on the neutralization pos-treatment process. PMID- 20355508 TI - Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices. AB - Big advances are being achieved in the design of new implantable devices with enhanced properties. For example, synthetic porous three-dimensional structures can mimic the architecture of the tissues, and serve as templates for cell seeding. In addition, polymeric nanoparticles are able to provide a programmable and sustained local delivery of different types of biomolecules. In this study novel alternative scaffolds with controlled bioactive properties and architectures are presented. Two complementary approaches are described. Firstly, scaffolds with nanogels as active controlled release devices incorporated inside the three-dimensional structure are obtained using the thermally induced phase separation (TIPS) method. Secondly, a novel coating method using the spraying technique to load these nanometric crosslinked hydrogels on the surface of two dimensional (2D) and three-dimensional (3D) biodegradable scaffolds is described. The scanning electron microscopy (SEM) images show the distribution of the nanogels on the surface of different substrates and also inside the porous structure of poly-alpha-hydroxy ester derivative foams. Both of them are compared in terms of manufacturability, dispersion and other processing variables. PMID- 20355509 TI - Synthesis and characterization of Ag-polymer nanocomposites. AB - We report the synthesis of Ag nanoparticles in polyethylene terephthalate (PET) matrix using atom beam co-sputtering. Metal filling factor was evaluated by Rutherford backscattering spectrometry. Microstructural evolutions of the nanocomposites films were investigated by transmission electron microscopy, which confirmed the formation of irregular shaped Ag nanoparticles. The X-ray photoelectron spectroscopy measurements of the sputter deposited PET film and co sputtered deposited Ag-PET as well as PET bulk foil (from Goodfellows) were performed to study chemical composition of the nanocomposite films. The optical properties of these nanocomposites were studied by light absorption/transmission, which revealed a narrow transmission of UV light approximately 320 nm and a broad surface plasmon resonance absorption extending up to infrared region (approximately 2400 nm). Swift heavy ion irradiation of Ag-PET nanocomposite resulted in narrowing the full width at half maximum of transmission band. PMID- 20355510 TI - Towards optimization of time modulated chemical vapour deposition for nanostructured diamond films on Ti6Al4V. AB - In this paper, we report the use of the TMCVD technique for the optimisation of deposited diamond films onto Ti6Al4V substrates. A number of samples were made varying the experimental parameters. The specimen surfaces were characterised using micro Raman spectra and SEM analyses. Results show that very different surface finish (from micro to nanostructures) and film characteristics can be obtained from the experimental parameters used. The quality of deposited diamond is very dependant on the experimental settings and process. It was found that lower residual stresses are developed using the TMCVD technique than with conventional CVD but depend on the structural diamond growth during the process. The quality of the deposited film was evaluated as a function of diamond to amorphous carbon ratio but showed no direct relation with the surface finish since it characterises the quality of the deposited diamond but not the quality of the film surface. PMID- 20355511 TI - Use of functionalized nanosilica to improve thermo-mechanical properties of epoxy adhesive joint bonding aluminium substrates. AB - The present work is concerned with the improvement of thermal properties and mechanical strength of adhesive joints consisting of an epoxy adhesive layer bonding aluminium substrates by grafted nanosilica. Epoxy resin/silica nanocomposites were prepared by using functionalized silica. Silica was functionalized by amine group (SiO2-NH2). It was identified by Raman and Fourier Transform Infrared (FTIR). Effects of silica on viscoelastic properties for epoxy resin and its assemblies with aluminium substrates were studied by Dynamical Mechanical Analysis (DMA). Particles distribution was characterized by Scanning Electron Microscope (SEM). Our experimental results showed that functionalized silica presents a better distribution in the matrix than the pure silica. Our results also showed that grafting of functionalized silica improves the glass transition temperature (Tg) and the ultimate strength of aluminium/epoxy/aluminium assembly. PMID- 20355512 TI - Ball milling of an equiatomic sigma--feV alloy in vacuum. AB - A coarse-grained tetragonal sigma phase Fe47.4V52.6 at% alloy was ground in vacuum in a vibratory mill. The sigma phase transforms into a bcc alpha phase. A concomitant partial amorphization of the bcc phase occurs. The near-equiatomic FeV alloys are concluded to behave in the same way as the related FeCr alloys when they are ball-milled in vacuum in similar milling conditions. In the stationary state of milling, about half of the iron atoms are contained in an amorphous phase both for sigma-FeCr and for sigma-FeV. PMID- 20355513 TI - Carboxymethyl cellulose-assisted hydrothermal synthesis of PbS with nano- and micro-crystals. AB - PbS with nano- and micro-crystals was hydrothermally synthesized from Pb(NO3)2 and thiosemicarbazide using carboxymethyl cellulose (CMC) as a template at 140, 180 and 200 degrees C for 12 h. CMC, NaOH and hydrothermal temperatures have the influence on the product morphologies characterized using a scanning electron microscope (SEM) and a transmission electron microscope (TEM). PbS (cubic) composing of Pb and S was detected using an X-ray diffractometer (XRD), a selected area electron diffraction (SAED) technique and an energy dispersive X ray (EDX) analyzer. The interpreted patterns are in accordance with those of the simulations. Raman spectrometer revealed the presence of the vibration modes at 136, 278, 432, 602 and 967 cm(-1). Emission spectra of the products were detected at 384-388 nm using a photoluminescence (PL) spectrometer. PMID- 20355514 TI - Investigation of surface plasmon resonance in gold/alumina composite films prepared by rf-sputtering. AB - Alumina films containing gold nanoparticles (NPs) were grown by magnetron radio frequency (rf) sputtering technique. They were investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD) and optical absorption spectroscopy. It is suggested that the increase of the contrast of surface plasmon resonance band after annealing is connected with increasing of electron free mean path in Au NPs rather than with change in particle size distribution. The absorption spectra of the nanocomposites have been modelled taking into account a correction of the dielectric constant for electron mean free path limitation. PMID- 20355515 TI - Preparation and thermal-mechanical characterization of nanoclay-unsaturated polyester composites. AB - Recently polymer nanocomposites have attracted great interest as much as in industry as in research laboratories, due to they often show remarkable improvement in their mechanical and thermal properties when are compared with the virgin polymers. Among nanocomposites, nanoclay-reinforced polymers have been widely studied, specifically, those formed by a thermosetting polymer matrix, like unsaturated polyester crosslinked resin reinforced with layered silicates, like montmorillonite. In this work we have prepared nanocomposites formed by an isophtalic unsaturated polyester crosslinked resin (UP) reinforced with different contents (2-10 wt%) of organic modified montmorillonite (OMMT). The UP/OMMT nanocomposites have been prepared following different procedures and the structural characterization has been carried out by using X-ray diffraction (XRD). In all the cases an increase of the d-spacing between layers of the OMMT has been detected. The objective of this study is to analyze the thermal and mechanical behaviour of nanocomposites. For all of the reinforced systems, the glass transition temperatures values, Tg, obtained by differential scanning calorimetry (DSC) and dynamic-mechanical thermal analysis, (DMTA) are higher than the corresponding ones to neat UP. On the other hand, the OMMTP mechanical behaviour has been evaluated by DMTA and by tensile tests. Both techniques reveal an increase in Young modulus, however, a decrease of the tensile strength is observed in all the reinforced systems. PMID- 20355516 TI - Curing and dynamic mechanical thermal properties of epoxy/clay nanocomposites. AB - Epoxy/Clay nanocomposites with two organically modified montmorillonites (Cloisite 30B and Cloisite 15A) have been prepared. Cloisite 15A has higher cation exchange capacity, interlayer spancing and hydrofobicity than Cloisite 30B. Different methods were carried out to disperse the clay in the epoxy monomer (diglycidyl ether of bisphenol A) with and without solvent, using stirring and ultrasound sonication. The epoxy hardeners used were 4,4'-diaminodiphenylmethane and 4,4'-diaminodiphenylsulfone which generate high glass transition temperature epoxy thermosets. The content of clay in the nanocomposites ranged from 2 to 11 wt%. The effect of Cloisites on the curing reaction has been studied by differential scanning calorimetry, finding that the presence of Cloisite 30B accelerates the curing reaction. The glass transition temperature of the epoxy thermoset decreases when the clay content increases, due to the plasticizing effect of the alkylammonium cations. The dispersion of the layered silicates within the crosslinked epoxy matrix was studied by wide-angle X-ray diffraction. In all the cases, the nanocomposites show intercalated clay structures, being the interlayer clay spacing almost independent of the method of dispersion, of the clay content, and of hardener used. Moreover the d-spacing differences between C30B and C15A nanocomposites are insignificant. Epoxy molecules intercalate in a smaller proportion in C15A than in C30B, as it was deduced from the increase of the d-spacing. The dynamic mechanical thermal properties of these nanocomposites were also investigated. Nanocomposites with Cloisite 30B show higher values of storage modulus than neat epoxy, both in the glassy and in the rubbery states. However Cloisite 15A does not improve the epoxy storage modulus, and such divergent behavior agrees with the different intercalation of epoxy in the clays. The fracture surfaces of the nanocomposites analyzed by environmental scanning electron microscopy indicate an improvement of toughness. PMID- 20355517 TI - Oleate-LDH hybrids by the successive use of the clay structural "memory effect". AB - Oleate/LDH composites have been obtain by calcination-reconstruction procedures by the successive uses of the anionic clay memory effect. XRD and FTIR analysis were used to study the structural characteristics of the hybrid samples. The amount of oleate in the hybrid formulation of the clay matrix is highest after the second calcination-reconstruction cycle. After the fourth cycle the clay structure is not recovered anymore. This result points out to the "short" structural "memory" of the LDH-like clays. Textural features of the samples were studied by N2 adsorption at 77 K, SEM and TEM analyses. The oleate/LDH hybrids, obtained by the successive uses of the clay "memory", are defined by different crystallinity and micromorphological characteristics. PMID- 20355518 TI - Molybdenum interlayers for nucleation enhancement in diamond CVD growth. AB - The use of a 50-nm thick Mo interlayer on silicon substrates for the nucleation enhancement of microcrystalline diamond (MCD) and nanocrystalline diamond (NCD) films synthesized by hot filament chemical vapour deposition was studied. The MCD and NCD films were deposited using methane concentrations of 1% and 2%, respectively. The presence of a Mo nucleation layer enabled the formation of more uniform NCD films with reduced surface roughness (rms roughness approximately 40 nm for a 750-nm thick layer) and with significantly less interfacial voids due to the superior nucleation densities and surface coverage in the early stages of NCD film formation. During the initial stages of MCD film growth, the nucleation density increased by one order of magnitude as compared to uncoated silicon. As a result, much thinner MCD films with smaller surface grain sizes and, thus, reduced surface roughness could be produced as well. The presence of a Mo nucleation layer not only leads to a structural optimization of NCD and MCD films but also allows fast nucleation and film growth kinetics at relatively low substrate temperatures (approximately 575 degrees C), relevant for the coating of substrate materials that do not withstand high substrate temperatures. PMID- 20355519 TI - Effect of aging temperature on formation of sol-gel derived fluor-hydroxyapatite nanoparticles. AB - Synthetic hydroxyapatite (HA) has been recognized as one of the most important bone substitute materials in orthopaedics and dentistry over past few decades because of its chemical and biological similarity to the mineral phase of human bone. One solution for reduction the solubility of HA in biological environments is replacing F- by OH in HA structure and forming fluor-hydroxyapatite (FHA) solid solution. In this paper, FHA nanoparticles were successfully synthesized by a sol-gel method. Also, the influence of aging temperature on formation of FHA powder was studied. Equimolar solutions of calcium nitrate tetrahydrate, triethyl phosphite and ammonium fluoride in ethanol were used as Ca, P and F precursors. After aging at different temperatures, the synthesized powders were heat treated at 550 degrees C. The powders were investigated with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), selected area electron diffraction pattern (SAED), energy dispersive analysis of X-ray (EDAX) and zetasizer measurement. The results of XRD proved the presence of fluorapatite (FA) and HA in all samples. In addition, the formation of FHA was confirmed by FT-IR results. XRD studies also showed that the crystallites were in nanometric scale. At the same time, this result was in good agreement with the result of zetasizer analysis. PMID- 20355520 TI - Preparation of magnetic nano-composite: barium hexaferrite loaded in the ordered meso-porous silica matrix (MCM-41). AB - In this work a magnetic nano-composite was synthesized by modified incorporation of iron-barium complex into ordered meso-porous silica (MCM-41) as a matrix. The MCM-41 was synthesized by silylation treatment which was accompanied by pH adjusting. Low angle XRD patterns of both annealed MCM-41 and resulted composite exhibited the characteristic reflection of high quality hexagonal meso structures. TEM image of the composite material revealed that the hexagonal ordered meso-structure host material was not affected by wet impregnation and subsequent calcination in order to incorporate with barium hexaferrite. Also, TEM images accompanied by EDS analysis confirmed the formation of second phase consists of barium and iron ions inside the MCM-41 channels. The resulted composite material showed a super-paramagnetic nature at room temperature. PMID- 20355521 TI - Molecular and electronic properties transferred to Silicon via wet-chemistry surface nanofunctionalization: ethynylferrocene on Si(100). AB - In the frame of our research activity on covalent anchoring of functional molecules on Si oriented surfaces, we report here on the hybrid species resulting from the reaction of ethynylferrocene with H-Si(100) either in a single, direct step, or after production of a self-assembled alpha,omega-bifunctional alkyl monolayer. In the former approach, a short Si-C covalent bond is established through visible-light activation of the unsaturated side arm of ethynylferrocene via an extra-mild approach. In the latter case, an azide-alkyne Huisgen cycloaddition reaction ("click" chemistry) is induced between the C[triple bond]C group of the molecule and the -N3 terminations of undecyl hydrocarbon chains pre assembled onto H-Si(100). These two routes lead to electroactive monolayers wherein the ferrocene head groups are respectively located close to or far from the Si surface. This allows for a fine tuning of the properties of the resulting hybrids on Si, in terms of distinct redox potentials, electron transfer rate constants, oxidation resistance. The different reaction steps have been monitored with X-ray Photoelectron Spectroscopy (XPS), in order to evaluate the presence and the chemical nature of the anchored species, while electrochemical measurements have evidenced reversible redox responses of the resulting SAMs. PMID- 20355522 TI - Synthesis of poly(methyl methacrylate)/ montmorillonite nanocomposites using a 3 D surfactant as an organic modifier. AB - Poly(methyl methacrylate)/Montmorillonite clay nanocomposites were synthesized via the free radical polymerization of methyl methacrylate in the presence of alkyl ammonium substituted polysilsesquioxane surfactant-modified clay and AIBN initiator in ethanol and aqueous ethanol solvent. MMT clay was initially cation exchanged with the surfactant to enhance its hydrophobicity and to expand the interlamellar spaces of silicate platelets. The 3-D structured surfactant and water molecules reduce the surface energy of the clay dramatically, which promotes miscibility of polymer/ clay nanocomposites. The intercalation and dispersion of clay were quantified by both X-ray diffraction and transmission electron microscopy, and the morphologies of the nanocomposites were observed by scanning electron microscopy. Both the alkyl ammonium polysilsesquioxane surfactant and filler clay enhanced thermal and mechanical properties of the nanocomposites as investigated with thermo gravimetric analysis and differential scanning calorimetry. PMID- 20355524 TI - Coherent transport in high performance double magnetic junctions. AB - Spin-dependent transport is considered in double magnetic tunnel junctions of two types F-I-F-I-F and F-I-N-I-F with thin insulating (I) barriers between the ferromagnetic (F) or non-magnetic (N) electrodes. Using the Landauer formalism within single-band tight-binding dynamics for atomically perfect epitaxial multilayers, the dependencies of tunnel magnetoresistance (TMR) on the on-site atomic energies epsilonI or epsilonN and number nI of atomic planes in the respective layers are obtained. It is found that the maximum TMR corresponds to the "shallow band" regime with respect to epsilonN and a series of peaks appears with respect to nI, essentially enhancing the performance of a simple F-I-F junction. These results suggest the material and structural choices for optimum TMR devices of advanced compositions. PMID- 20355523 TI - Biocompatible nanoparticles intercalated with anticancer drug for target delivery: pharmacokinetic and biodistribution study. AB - We have developed new hybrid systems consisting of anticancer drugs such as methotrexate (MTX) or 5-fluorouracil (5-FU) and two-dimensional inorganic delivery carrier like layered double hydroxide (LDH). Such an inorganic vector with biocompatible metal ions can be used to overcome toxicity, immunogenecity and poor integration capacity, which are critical problems caused by conventional viral vectors, cationic liposomes and polymers. Moreover, the intercellular mechanism of LDH nanoparticles is primarily related to clathrin-mediated endocytosis, resultihg in effective delivery and eventually enhancing drug efficacy. In this report, the effect of LDH intercalated with 5-Fu (5-Fu-LDH) was evaluated in whole animal by studying pharmacokinetic behavior and tissue distribution. The results showed that 5-Fu-LDH exhibited favorable blood clearance profiles compared to free 5-Fu, such as sustained drug release, prolonged drug half-life, and increased drug accumulation in target tumor tissue. Furthermore, LDH nanoparticles were rapidly excreted from the body and not accumulated in the organs after administration as 5-Fu-LDH. Therefore, the hybrid system can be promising anticancer chemotherapy agent for tumor targeting with biocompatibility. PMID- 20355525 TI - Optical properties of Nd3+ doped ionic liquid immobilized on mesoporous silica support. AB - The synthesis of a new material based on Nd3+ ions doped into an imidazolium-type ionic liquid with further immobilization on a mesoporous silica support is reported. The material was investigated by DR-UV/VIS, FT-IR, thermogravimetric analysis, N2 adsorption measurements and time-resolved photoluminescence spectroscopy. The intensity of the near-infrared emission of Nd3+ was weak and the lifetime measured at about 910 nm was 7 micros. PMID- 20355527 TI - Synthesis of ZnO nanostructures using different metal catalyst: morphology and photoluminescence characteristics. AB - In the present study, we report the synthesis of ZnO nanostructures using the Vapor-Liquid-Solid growth with different metal catalyst by electron beam evaporation method. As grown samples were characterized by means of Field emission scanning electron microscopy (FESEM), Raman spectroscopy and photoluminescence spectroscopy. FESEM characterization showed the formation of different type of nanostructure depending on the metal catalyst. Array of well aligned nanorods were formed when Au and Fe were used as a catalyst. However, Sn catalyst induced the formation of nanoflakes. The presence of peak at 434 cm(-1) in Raman spectroscopy revealed the wurtzite nature of formed ZnO nanostructures. Nanoflakes showed a more strong UV emission in comparision to that of nanorods as revealed by Photoluminescence spectra. PMID- 20355526 TI - Ti-Si-C thin films produced by magnetron sputtering: correlation between physical properties, mechanical properties and tribological behavior. AB - Ti-Si-C thin films were deposited onto silicon, stainless steel and high-speed steel substrates by magnetron sputtering, using different chamber configurations. The composition of the produced films was obtained by Electron Probe Micro Analysis (EPMA) and the structure by X-ray diffraction (XRD). The hardness and residual stresses were obtained by depth-sensing indentation and substrate deflection measurements (using Stoney's equation), respectively. The tribological behavior of the produced films was studied by pin-on-disc. The increase of the concentration of non-metallic elements (carbon and silicon) caused significant changes in their properties. Structural analysis revealed the possibility of the coexistence of different phases in the prepared films, namely Ti metallic phase (alpha-Ti or beta-Ti) in the films with higher Ti content. The coatings with highest carbon contents, exhibited mainly a sub-stoichiometric fcc NaCI TiC-type structure. These structural changes were also confirmed by resistivity measurements, whose values ranged from 10(3) omega/sq for low non-metal concentration, up to 10(6) omega/sq for the highest metalloid concentration. A strong increase of hardness and residual stresses was observed with the increase of the non-metal concentration in the films. The hardness (H) values ranged between 11 and 27 GPa, with a clear dependence on both crystalline structure and composition features. Following the mechanical behavior, the tribological results showed similar trends, with both friction coefficients and wear revealing also a straight correlation with the composition and crystalline structure of the coatings. PMID- 20355528 TI - Nanostructured silicon based thin film transistors processed in the plasma dark region. AB - Nanostructured silicon (na-Si:H) thin films were fabricated using plasma enhanced chemical vapour deposition (PECVD) technique under high silane hydrogen dilution and a discharge frequency of 27 MHz, where the substrate was located in the dark region of the plasma, protected by a grounded metal grid. By not exposing the growth surface directly to the plasma we avoid the silicon growth surface to sustain a high ion bombardment leading to a less defective surface and highly compact films. The intrinsic films grown under these conditions were used to produce the channel region of thin film transistors (TFTs) with a bottom gate staggered configuration, integrating different dielectric layers. The devices produced exhibit a field effect mobility close to 1.84 cm2 V(-1) s(-1), threshold voltage around 2 V, on/off ratio above 10(7) and sub-threshold slope below 0.5 V/decade, depending on the dielectric used. PMID- 20355529 TI - Giant room temperature magnetoimpedance in La0.7Ba0.15Sr0.15MnO3 and development of a sensitive position detector. AB - Observation of room temperature giant magnetoimpedance in La0.7Ba0.15Sr0.15MnO3 compound having nanometric grain size is reported under low magnetic field and over the frequency range between 50 KHz and 15 MHz. Both the resistive and reactive components of impedance increase with increasing frequency due to skin effect of the metallic state below T(C). Above a critical frequency (1 MHz), a sharp increase in both R and X and hence Z is observed. The applied magnetic field influences the impedance by affecting the penetration depth via the transverse permeability and gives rise to large magnetoimpedance (approximately 70%) at low fields up to 0.1 T. Magnetoimpedance of La0.7Ba0.15Sr0.15MnO3 compound display major change (approximatley 61%) between 0.02 and 0.035 T and appears to originate due to the spin alignment of the charge carriers across the grain boundaries. At fields > 0.1 T, magnetoimpedance displays near saturation, corresponding to the completion of the spin alignment across the grain boundaries. An unique scaling behavior has been observed for field dependence of magnetoimpedance at various frequencies, which could be well accounted by a phenomenological model. Feasibility of the development of a sensitive linear position sensor is also demonstrated. PMID- 20355530 TI - Micromechanically-based formulation of the cooperative model for the yield behavior of starch-based nano-biocomposites. AB - The tensile yield stress of plasticized starch filled with montmorillonite has been studied as a function of the temperature and the strain rate and has been compared to the yield behavior of the original matrix. Aggregated/intercalated and exfoliated nano-biocomposites, obtained from different nanofillers, have been produced and tested under uniaxial tension (tensile test). To model the nanocomposite tensile yield stress behavior, a preexisting micro-mechanically based cooperative model, which describes properly the yield of semi-crystalline polymers has been modified. According to our development, the yield behavior of nano-biocomposites is strongly dependant on the clay concentration and exfoliation ratio. Based on the thermodynamics properties, an effective activation volume and effective activation energy are computed through the Takayanagi homogenization model. The predicted results for the yield stress at low strain rates and at different temperatures are in agreement with our experimental results. PMID- 20355531 TI - Investigation of the stiffness and yield behaviour of melt-intercalated poly(methyl methacrylate)/organoclay nanocomposites: characterisation and modelling. AB - The elastic modulus and yield stress behaviour of a melt intercalated Poly(methylmethacrylate)/ organoclay (PMMA/C30B and PMMA/C20A) were studied using uniaxial tensile tests at different temperatures and different strain rate. The stress-strain response was obtained for different loading rates and different test temperature. Both the stiffness and the yield stress were then clearly identified as function of strain rate and temperature. Our experimental results show that the yield stress and modulus of both PMMA/C20A and PMMA/C30B organoclay nanocomposites are very sensitive to clay concentration, strain rate and temperature. A micromechanically-based composite approach was used to predict the yield stress of both PMMA/C20A and PMMA/C30B organoclay nanocomposites. The results obtained from the model are in good agreement with our experimental results. As expected, the activation enthalpy of cooperative model increased slightly while the activation volume decreases slightly with the clay concentration. PMID- 20355532 TI - A special issue on nanooptics and nanophotonics. PMID- 20355533 TI - Luminescence nanocrystals for solar cell enhancement. AB - Semiconductor nanocrystals (NCs) prepared by wet-chemical routes have been proposed as an attractive candidate for fabrication of the third-generation thin film solar cells due to their quantum confinement effects and excellent dispersion ability in polymer films. However, to date, a solar cell incorporating semiconductor NCs in the photoactive layer still has rather low efficiency due to the low carrier mobility of the non-continued NC phase and the possible radiative recombination in NCs. To avoid these disadvantages, NCs have been proposed and applied as a luminescent species in a passive photon converting layer to modify the solar spectrum before the light enters the photovoltaic device. Photon conversion processes, including up-conversion, down-conversion, and down shifting, have been observed in various colloidal NC samples and have great potential to enhance photovoltaic performance when applied to the existing single junction solar cells or narrow-band molecular-based devices. PMID- 20355534 TI - Nanowire photodetectors. AB - The use of nanowires and nanowire structures as photodetectors is an emerging research topic. Despite the large amount of reports on nanowire photoresponse that appeared in the literature over the last decade, the mechanism leading to high photosensitivity and photoconductive gain in high aspect ratio nanostructures has been elucidated only recently. Novel device architectures integrated in single nanowire devices are also being actively studied and developed. In this article, the general nanowire photodetector concepts are reviewed, together with a detailed description of the physical phenomena occurring in nanowire photoconductors and phototransistors, with some examples from recent experimental results obtained in our groups. An outlook on future directions toward the use of semiconductor nanowire photoconductors as intrachip interconnects, single-photon detectors, and image sensors, is also given. PMID- 20355535 TI - Progress and prospects for quantum dots in a well infrared photodetectors. AB - Over the past fifteen years, there has been significant interest in developing intersubband quantum dot (QD) detectors for the mid-(MWIR) and long-wave infrared (LWIR) regimes. This class of detectors is generally referred to as quantum dot infrared photodetectors, or QDIPs. At present, one of the leading technologies is that of the quantum dots-in-a-well infrared photodetector, called a DWELL-IP or just a DWELL detector. The DWELL name comes from the active region's structure, which consists of a layer of quantum dots imbedded in (or in some cases grown on) a quantum well. This dot/well combination is similarly surrounded by a barrier material. Here, we identify the major players and their contributions to the evolution of the DWELL-IP. While this dot/well/barrier material combination originally consisted of InAs/InGaAs/GaAs, the materials used has widened in recent years. This paper reviews the progress to date for this quickly advancing field. Some of these advancements have come from the additional focus that has been brought to bear on the physical understanding and experimental mechanics of the structure itself. Explorations into the multi-spectral nature of these detectors have also created unique applications for these detectors. This type of QDIP is now becoming the dominant detector of its class and is quickly heading for parity with quantum well infrared photodetectors (QWIPs) that are presently commercially dominant. Given the potential utility of the infrared spectrum for applications in medicine, military, industrial, and academic fields the DWELL-IPs potential to be an inexpensive, versatile, multi-spectral, infrared detector indicates it has a bright future. PMID- 20355536 TI - III-V/silicon-on-Insulator nanophotonic cavities for optical network-on-chip. AB - We review some opto-electronic devices based on the III-V/SOI heterogeneous integration platform, including lasers, modulators, wavelength converters, and photo-detectors. All of them are critical components for future on-chip interconnect and optical network-on-chip. The footprints of such devices are kept small by employing micro-cavity based structures. We give an overview of the device performances. The advantages over the all-silicon based devices are also discussed. PMID- 20355537 TI - Photonic crystal negative refractive optics. AB - Photonic crystals (PCs) are multi-dimensional periodic gratings, in which the light propagation is dominated by Bragg diffraction that appears to be refraction at the flat surfaces of the PC. The refraction angle from positive to negative, perfectly or only partially obeying Snell's law, can be tailored using photonic band theory. The negative refraction enables novel prism, collimation, and lens effects. Because PCs usually consist of two transparent media, these effects occur at absorption-free frequencies, affording significant design flexibility for free-space optics. The PC slab, a high-index membrane with a two-dimensional airhole array, must be carefully designed to avoid reflection and diffraction losses. Light focusing based on negative refraction forms a parallel image of a light source, facilitating optical couplers and condenser lenses for wavelength demultiplexing. A compact wavelength demultiplexer can be designed by combining the prism and lens effects. The collimation effect is obtainable not only inside but also outside of the PC by optimizing negative refractive condition. PMID- 20355538 TI - Optical spectroscopy of rare earth ion-doped TiO2 nanophosphors. AB - Trivalent rare-earth (RE3+) ion-doped TiO2 nanophosphors belong to one kind of novel optical materials and have attracted increasing attention. The luminescence properties of different RE3+ ions in various TiO2 nanomaterials have been reviewed. Much attention is paid to our recent progresses on the luminescence properties of RE3+ (RE = Eu, Er, Sm, Nd) ions in anatase TiO2 nanoparticles prepared by a sol-gel-solvothermal method. Using Eu3+ as a sensitive optical probe, three significantly different luminescence centers of Eu3+ in TiO2 nanoparticles were detected by means of site-selective spectroscopy at 10 K. Based on the crystal-field (CF) splitting of Eu3+ at each site, C2v and D2 symmetries were proposed for Eu3+ incorporated at two lattice sites. A structural model for the formation of multiple sites was proposed based on the optical behaviors of Eu3+ at different sites. Similar multi-site luminescence was observed in Sm(3+)- or Nd(3+)-doped TiO2 nanoparticles. In Eu(3+)-doped TiO2 nanoparticles, only weak energy transfer from the TiO2 host to the Eu3+ ions was observed at 10 K due to the mismatch of energy between the TiO2 band-gap and the Eu3+ excited states. On the contrary, efficient host-sensitized luminescences were realized in Sm(3+)- or Nd(3+)-doped anatase TiO2 nanoparticles due to the match of energy between TiO2 band-gap and the Sm3+ and Nd3+ excited states. The excitation spectra of both Sm(3+)- and Nd(3+)-doped samples exhibit a dominant broad peak centered at approximately 340 nm, which is associated with the band gap of TiO2, indicating that sensitized emission is much more efficient than direct excitation of the Sm3+ and Nd3+ ions. Single lattice site emission of Er3+ in TiO2 nanocrystals can be achieved by modifying the experimental conditions. Upon excitation by a Ti: sapphire laser at 978 nm, intense green upconverted luminescence was observed. The characteristic emission of Er3+ ions was obtained both in the ultraviolet-visible (UV-vis) and near-infrared regions through the high-resolution experiments at 10 K. The CF experienced by Er3+ in TiO2 nanocrystal was systematically studied by means of the energy level fitting. PMID- 20355539 TI - Photonic crystal ring resonators: characteristics and applications. AB - We review the characteristics and applications of photonic crystal ring resonators (PCRRs), which can potentially provide a good alternative to the traditional micro ring resonators, as one of the key contributors to the emerging low-power nanophotonic technology. Applying numerical analysis together with the theory of mode superposition, the properties of PCRRs have been comprehensively investigated. We will report PCRR key characteristics, including diameter (D) dependent loss, quality factor (Q), and free spectral range (FSR). No size dependent loss was found in PCRRs, unlike the approximately 1/D dependent loss in micro-strip resonators, making PCRRs a promising candidate for ultra-compact ring resonators. PMID- 20355540 TI - Microresonators in CMOS compatible substrate. AB - We report our recent progress in designing and developing traveling-wave microresonators on CMOS compatible substrate, with a focus on ultra-compact Si based microring and microdisk resonators in the visible and near infrared wavelengths with ultra-high Q and small mode volume, suitable for strong light matter interaction. The performance of these resonators is discussed, and the design and fabrication challenges and solutions to achieve efficient coupling from the bus-waveguide to the resonator is mentioned. Coupled-resonator architectures for the design of filters are analyzed and theoretical and experimental results for the flat-band filters with wide bandwidth and large free spectral range are presented. Furthermore, by using a detailed thermal model we demonstrate optimized microresonator structures on semiconductor substrates with improved thermal conductivity that can sustain a high circulating optical intensity at the resonance wavelength, which is particularly useful for nonlinear optics and optical signal processing applications. Finally, we address some of the applications and future prospects of such microresonators in CMOS-compatible substrate technology, including portable multi-purpose bio/chemical sensing systems, reconfigurable optical signal processing modules and chip-scale optical amplifiers and lasers. PMID- 20355541 TI - Growth and characterization of self-assembled InAs/InP quantum dot structures. AB - InAs quantum dots (QDs) are grown on InP or lattice matched GaInAsP buffers using horizontal flow metal-organic chemical vapor deposition (MOCVD) at a pressure of 180 mbar. A range of techniques, such as photoluminescence (PL), atomic force microscopy, and plan-view transmission electron microscopy is used to characterize the QD and other semiconductor layers. The effects of different growth parameters, such as V/III ratio and growth time, and the effects of buffer layers, interlayers, and cap layers are investigated and the optimized growth conditions are discussed. In the case of the QDs grown on InP buffers, the As/P exchange reaction is found to be prominent. A very thin (0.6 nm) GaAs interlayer grown between the buffer and the QD layers consumes segregated indium and minimizes the As/P exchange reaction. As a result, the QD PL emission energy increases, the PL intensity improves, and the PL linewidth decreases. The experimental results show that by changing the thickness of a GaAs interlayer (0.3-0.6 nm), the emission wavelength/energy of the QDs grown on a lattice matched GaInAsP buffer can be tuned over a wide range covering 1550 nm. However, further increase in the thickness of the GaAs interlayer results in the agglomeration of the QDs and the deterioration of the QD optical properties. Detailed microscopy studies show that capped QDs have higher density and are smaller in size on average compared to uncapped QDs, which undergo coalescence during cooling of the sample after growth. Overall, the QDs grown for shorter time with a smaller V/III ratio (approximately 8) show improved PL intensity and narrower PL linewidth. PMID- 20355542 TI - InAs quantum dots on nanopatterned GaAs (001) surface: the growth, optical properties, and device implementation. AB - This work reviews the growth, optical properties, and device implementation of InAs semiconductor quantum dots (QDs) selectively nucleated atop nano-faceted GaAs pyramidal structures grown by metal-organic chemical-vapor deposition. This site-controlled QD growth technique offers unique features and benefits subsequent device applications. First, GaAs pyramids, formed on a SiO2-masked and nanopatterned (001) GaAs substrate, are characterized by well-defined equilibrium crystal shapes (ECS). The controlled ECS formation is crucial to subsequent patterned QD (PQD) nucleation, which is highly preferential toward {11n} planes due to superior QD energy minimization. Second, PQD optical properties are thoroughly studied by monitoring room temperature (RT) photoluminescence (PL) and power-dependent low-temperature PL to verify the crystalline quality and the three-dimensional quantum confinement. The PQD ensembles formed on different GaAs pyramids, with different PL behavior, indicate lateral coupling within QD clusters and characteristics of isolated QD pairs. Then, PQDs embedded in a InGaAs quantum well, the so-called dot-in-the-well (DWELL) structure, are compared to a self-assembled QD (SAQD) DWELL structure, and shown to have a better emission efficiency, due to the distributed QW thickness profile on the faceted GaAs pyramid. Finally, broad-area light emitting diodes based on the PQD active region are fabricated. Linear current-voltage characteristics are observed with sharp turn-on, low leakage current and low forward resistance. Electroluminescence spectra show PQD intraband structure and low quenching of emission from 77 K to room temperature. Light-current measurements demonstrate external quantum efficiency per PQD comparable to SAQDs, despite the two regrowth steps in the fabrication processes. PMID- 20355543 TI - Bridging the gap between nanophotonic waveguide circuits and single mode optical fibers using diffractive grating structures. AB - In this paper, the use of diffractive grating structures to efficiently interface between a single mode fiber and a high index contrast waveguide circuit is outlined. We show that high index contrast grating structures allow for broadband and high efficiency coupling. Since no polished facet is required on the photonic integrated circuit to interface with the optical fiber, fiber-to-chip grating couplers enable wafer-scale testing, reducing the cost for testing large scale integrated optical circuits. We show that two-dimensional grating structures can solve the problem of the huge polarization dependence of high index contrast photonic integrated circuits. Finally, an optical probe is presented, which allows testing individual components of a photonic integrated circuit, analogous to the electrical probes used in micro-electronics. PMID- 20355544 TI - A review on inorganic nanostructure self-assembly. AB - In recent years, there has been a growing interest in the self-assembly process for the fabrication of micro- and nano-scale structures for various device applications. The success of these applications requires the development of a versatile assembly process for producing large area ordered arrays. In this article, we review recent advances, particularly related to photonic material and device applications, based on self-assembly processes, with the focus on the processes for inorganic structure self assembly. We first discuss major forces guiding the particle self-assembly in the wet coating technology. Then we review device applications and recent advances based on three kinds of wet coating technologies, including dip coating, spin coating and convective coating. Finally, a conclusion will be given, with discussions given on future perspectives. PMID- 20355545 TI - Light emission from nanoscale Si/Si oxide materials. AB - Most porous Si materials studied have been oxidized in various degrees. The oxidized porous Si comprises of a great quantity of nanoscale Si particles (NSPs) and each of them is covered by a Si oxide layer. The structure and luminescence properties of the NSPs embedded Si oxide and the nanoscale Si/nanoscale SiO2 multilayers are similar to those of the oxidized porous Si. All the three kinds of materials mentioned are called nanoscale Si/Si oxide materials and their photoluminescence and electroluminescence properties especially light emission mechanisms are reviewed in this article. Nanoscale Si/Si oxide materials have been well studied and are believed to be very promising Si based light emitting materials. The very distinct roles of the NSPs and the luminescence centers in Si oxide in the photoluminescence and electroluminescence from the nanoscale Si/Si oxide materials are highlighted. PMID- 20355546 TI - Longitudinal and angular dispersions in photonic crystals: a synergistic perspective on slow light and superprism effects. AB - The slow-light effect and the superprism effect are two important effects in photonic crystal structures. In this paper, we will review some of our recent works on the fundamental physics and device applications of these two effects. We will present a synergistic perspective that examines these two effects as a whole. Apparently, the slow light effect is due to the dispersion of a photonic crystal along the direction of light propagation, namely the longitudinal direction, and the superprism effect is related to angular dispersion. However, a deep analysis will show that the superprism effect has an elusive dependence on the longitudinal dispersion as well. Some subtle connections and distinctions between the slow-light effect and the superprism effect will be revealed through our physical analysis. This allows us to treat these two effects under a common theoretical framework. As an example, we will apply this framework to make a direct comparison of the slow-light optical phase array approach and the superprism approach to beam steering applications. Dispersive effects are frequently accompanied by high optical loss and/or narrow bandwidths. We will discuss these issues for both longitudinal and angular dispersions. For the slow light effect, we will give a simple proof of the scaling of fabrication imperfection related random scattering losses in a slow-light photonic crystal waveguide. Similar to the bandwidth-delay product for the longitudinal dispersion, we will introduce a simple, yet fundamental, limit that governs the bandwidth and angular sensitivities of the superprism effect. We will also discuss the application of the slow-light effect to making compact silicon optical modulators and switches. PMID- 20355547 TI - Fabrication of guided-mode resonance elements by nanoimprint lithography. AB - This paper addresses utilization of nanoimprint lithography for fabrication of nanopatterned resonant photonic elements. These compact periodic films resonate sharply when illuminated with light. The attendant spectral and angular signatures are useful in design of photonic devices for various applications. It is of interest to design and optimize resonant leaky-mode elements with prescribed filtering, polarization, and security attributes. Applying nanoimprint lithography techniques, we fabricate prototype devices using polymer materials produced by Dymax Corporation. The initial prototypes are designed for use in the near-IR and telecommunications spectral regions. We apply holographic surface relief gratings as master templates. With these templates, we have formed submasters in PDMS (polydimethylsiloxane) to function as imprint stamps for the soft lithography steps. Using these submasters, we fabricate periodic surfaces in UV-curable polymers with resonant films deposited on the surface by sputtering. Several example devices possessing resonance efficiencies exceeding 90% are presented along with their spectral and angular characteristics. PMID- 20355548 TI - A macrochip interconnection network enabled by silicon nanophotonic devices. AB - We present an advanced wavelength-division multiplexing point-to-point network enabled by silicon nanophotonic devices. This network offers strictly non blocking all-to-all connectivity while maximizing bisection bandwidth, making it ideal for multi-core and multi-processor interconnections. We introduce one of the key components, the nanophotonic grating coupler, and discuss, for the first time, how this device can be useful for practical implementations of the wavelength-division multiplexing network using optical proximity communications. Finite difference time-domain simulation of the nanophotonic grating coupler device indicates that it can be made compact (20 microm x 50 microm), low loss (3.8 dB), and broadband (100 nm). These couplers require subwavelength material modulation at the nanoscale to achieve the desired functionality. We show that optical proximity communication provides unmatched optical I/O bandwidth density to electrical chips, which enables the application of wavelength-division multiplexing point-to-point network in macrochip with unprecedented bandwidth density. The envisioned physical implementation is discussed. The benefits of such an interconnect network include a 5-6x improvement in latency when compared to a purely electronic implementation. Performance analysis shows that the wavelength-division multiplexing point-to-point network offers better overall performance over other optical network architectures. PMID- 20355549 TI - Ultracompact photonic-waveguide circuits in Si-pillar photonic-crystal structures for integrated nanophotonic switches. AB - Highly integrated optical device technology based on square-lattice Si-pillar photonic-crystal-(PC) waveguides is described. The Si-pillar PC waveguides are now ready to use, since efficient optical coupling structures to Si-wire waveguides have been devised. Nanophotonic switches using the Si-pillar-PC waveguides were experimentally demonstrated. The nanophotonic switches make use of two of the features of Si-pillar photonic crystal waveguides. One is the property of slow-light and the other is the usability of zero-radius 90 degrees bends, both of which enable waveguide-based optical devices to be greatly miniaturized. Even apart from the cut-off wavelength, the group index of the pillar-PC waveguides was about 7.8, which was about twice that of a Si-wire waveguide for the entire C-band of telecommunications wavelengths. The 3-dB couplers we fabricated were only 3.2-microm long thanks to the 90 degrees sharp bends, and they operated throughout the entire C-band. Waveguide-cross operation was also demonstrated in the entire C-band. Asymmetric Mach-Zehnder interferometers (MZIs) were configured by using the 3-dB couplers in an area of 13.2 x 37.2 microm. An MZI with a Si-wire heater successfully operated with an extinction ratio of about 20 dB at a heating power of 17 mW. It is strongly suggested that Si-pillar PC photonic-waveguide technology should help us to achieve densely integrated optical-matrix switches demanded for future photonic telecommunication systems. PMID- 20355550 TI - Synthesis of nanocomposite materials with controlled structures and optical emissions: application of various methacrylate polymers for CdSe quantum dots encapsulation. AB - CdSe quantum dots (QDs) were incorporated in polymer films via in situ polymerization using one of the four different monomers having a varied hydrocarbon side chain length, namely, hexyl, lauryl, stearyl, or behenyl methacrylate. This technique resulted in the preparation of a series of the QD based nanocomposite materials for which laser scanned confocal microscopy imaging revealed a uniform dispersion of nanoparticles within the polymethacrylate matrices. Importantly, the polymer encapsulation of highly luminescent CdSe QDs did not affect their optical properties. The films exhibit the size-quantized optical effects characteristic of QDs. The changes in photoluminescence (PL) intensity of CdSe QDs were investigated as a function of illumination duration in different chemical environments, including the above polymeric matrices and a chloroform solution. Enhancement of the photoluminescence quantum yield for photoactivated QDs in methacrylate polymers was observed. This study of quantum yields of QD-based composites is important for understanding the involvement of surface states of photoactivated QDs as well for identifying ideal polymeric hosts for photoinduced surface passivation. PMID- 20355551 TI - Integration of silicon nanocrystals and erbium ring cavities for a silicon pumped Er:SiO2 laser. AB - In this work we present a novel two-stage approach to achieve electrically pumped lasing on a CMOS compatible material platform in the telecom region. The proposed design consists of an electrically pumped silicon nanocrystal (Si-nc) light source acting as an optical pump for an Erbium doped silicate (Er:SiO2) lasing cavity. The integrated design, based on concentric disks of Si-nc and Er:SiO2, provides a means of coupling the Si-nc pump signal to the Er ions without requiring overlap of the Er based lasing mode with the Si-nc material. We present an electromagnetic analysis of the pump and lasing modes in the proposed configuration. We also present fabrication and characterization of Si-nc and Er:SiO2 microdisks as components of the integrated design. PMID- 20355552 TI - Ultra-compact laser beam steering device using holographically formed two dimensional photonic crystal. AB - In this paper, we report the theoretical study of polymer-based photonic crystals for laser beam steering which is based on the superprism effect as well as the experiment fabrication of the two dimensional photonic crystals for the laser beam steering. Superprism effect, the principle for beam steering, was separately studied in details through EFC (Equifrequency Contour) analysis. Polymer based photonic crystals were fabricated through double exposure holographic interference method using SU8-2007. The experiment results showed a beam steering angle of 10 degree for 30 nm wavelength variation. PMID- 20355553 TI - Design of two-dimensional tunable photonic crystals with multiple functionalities. AB - Negative refraction is an interesting phenomenon which can provide sub-wavelength imaging and a novel way to control the propagation path of photons. Photonic crystals have been intensively researched to achieve negative refraction. In this article, we present design and simulations of a new two-dimensional tunable photonic crystal obtained using the plane wave expansion method. The newly designed photonic crystals exhibit tunability among positive, zero, and negative refractions, when liquid crystals infiltrated in the structures are electrically tuned. The equifrequency surface diagrams of the designed photonic crystal unveil the refraction direction of photons in the structures. The tunability is further confirmed using the finite-difference time-domain simulation. PMID- 20355554 TI - Nearly Gaussian dependence between near-infrared photoluminescence and O/Si composition ratio of Si-rich SiO(x) film with buried Si nanocrystals. AB - O/Si composition ratio optimized near-infrared (NIR) photoluminescence (PL) from Si nanocrystal (nc-Si) precipitated in Si-rich SiO(x) grown by Ar-diluted SiH4 and N2O is demonstrated. By detuning N2O fluence and N2O/SiH4 ratio to adjust the O/Si composition ratio of SiO(x) from 1.38 to 0.88, a nonlinearly Gaussian-like dependency of PL versus O/Si ratio with its maximum at O/Si of 1.24 is obtained. Maximized Si atomic density of 44.64 atom.% and nc-Si related PL of 25 count/nm is observed from SiO(x) with O/Si = 1.24 grown at N2O fluence of 50 sccm and N2O/SiH4 flowing ratio as low as 5.5. The FTIR analysis clearly indicates that the strong absorption bands at 870 and 2250 cm(-1) contributed by Si-H bonds suggests the hydrogen-passivated nc-Si could efficiently preserve the NIR PL response. Further reduction on O/Si composition ratio inevitably transfers the phase of host matrix from Si2O3 to SiO, which exhausts residual Si atoms and greatly decreases nc-Si density to degrade the PL response. PMID- 20355555 TI - Carboxyl-functionalized and bio-conjugated silica-coated quantum dots as targeting probes for cell imaging. AB - We report the synthesis of carboxyl-functionalized silica-coated CdSe/ZnS quantum dots (QDs) via a reverse microemulsion approach. This facile method does not need to change the solvent phase of the nanoparticles during the synthesis process, and requires no other reaction condition such as high temperature or inertia atmosphere. The synthesized nanoparticles have many advantages, such as mono dispersed and stable in aqueous solution, minimal non-specific targeting, and more direct and cost-effective for bio-conjugation. The carboxyl functionalized nanoparticles were further conjugated with apo-transferrin for receptor-mediated targeting in cancer cell lines. In vitro experiments have revealed that the cellular uptake of Tf-conjugated nanoparticles was significantly higher than that of (only-)carboxyl functionalized nanoparticles in HeLa cells, which are well known to overexpress the transferrin-receptor. The bio-conjugated nanoparticles are potentially useful as efficient probes for bio-diagnosis, both in vitro and in vivo. PMID- 20355556 TI - Application of far infrared rare earth mineral composite materials to liquefied petroleum gas. AB - Far infrared rare earth mineral composite materials were prepared by the coprecipitation method using tourmaline, cerium acetate, and lanthanum acetate as raw materials. The results of Fourier transform infrared spectroscopy show that tourmaline modified with the rare earths La and Ce has a better far infrared emitting performance. Through XRD analysis, we attribute the improved far infrared emission properties of the tourmaline to the unit cell shrinkage of the tourmaline arising from La enhancing the redox properties of nano-CeO2. The effect of the composite materials on the combustion of liquefied petroleum gas (LPG) was studied by the flue gas analysis and water boiling test. Based on the results, it was found that the composite materials could accelerate the combustion of LPG, and that the higher the emissivity of the rare earth mineral composite materials, the better the effects on combustion of LPG. In all activation styles, both air and LPG to be activated has a best effect, indicating the activations having a cumulative effect. PMID- 20355557 TI - Optical properties of ZnMgO nanowalls grown by plasma-assisted molecular beam epitaxy. AB - ZnMgO nanowalls were prepared by plasma-assisted molecular beam epitaxy without a catalyst on c-Al2O3 substrate. The obtained nanowalls have preferred orientation along c axis. The nanowalls are about 10 to 20 nm in thickness and about 50 nm in height. Only Zn, Mg, O and Al signals are detected in the nanowalls from the energy dispersive spectroscopy (EDS). The Mg content is about 3% in ZnMgO nanowalls. The room temperature photoluminescence (PL) spectra shows the emission peak of the ZnMgO nanowalls at 3.346 eV. The origin of the ultraviolet emission is discussed with the help of temperature-dependent PL spectra. The ultraviolet emission band is free exiton recombination observed in the low temperature PL spectra (at 81 K). We also observe the free-to-acceptor (FA) emission of the ZnMgO nanowalls. The acceptor binding energy obtained from photoluminescence studies is about 123 meV. The results show that Mg doping leads to an increase of the acceptor binding energy. The possible growth mechanism of the ZnMgO nanowall networks was discussed. PMID- 20355558 TI - A solvothermal route to size- and phase-controlled highly luminescent NaYF4:Yb,Er up-conversion nanocrystals. AB - Size-controlled hexagonal- and cubic-phase NaYF4:Yb,Er nanocrystals with bright fluorescent emission were successfully synthesized via a solvothermal approach at a relatively low temperature (< 300 degrees C). A mixture of ethanol and ethylene glycol or pure ethylene glycol was used as a solvent, whereby changing the ethanol concentration. It is found that, besides reaction temperature and time, the reactant concentration is an important factor to control crystal phase. High reactant concentration, high reaction temperature, high concentration of ethanol and long reaction durations are favorable to the formation of brightly emitting hexagonal-phase nanocrystals. The effects of these reaction conditions on the size and the luminescent properties of the as-prepared nanocrystals are discussed. It is found that 30-120 nm hexagonal NaYF4:Yb,Er nanoparticles can be prepared using 0.04 M reactant concentration in 0-60% ethanol solution at 220 degrees C for 24 h. PMID- 20355559 TI - Sensitized luminescence of Sm3+,Eu(3+)-codoped TiO2 nanoparticles. AB - Sm3+,Eu(3+)-codoped TiO2 nanoparticles were prepared by a facile sol-gel solvothermal method. Sm3+ and Eu3+ were successfully incorporated into a TiO2 lattice and resulted in intense emission lines with resolved crystal-field splitting, in spite of a large mismatch in ionic radius between trivalent lanthanides (Ln3+) and Ti4+. The intense sensitized emissions of Sm3+ and Eu3+ ions by TiO2 host were obtained at room temperature. In this case, Sm3+ also acts as a bridge to transfer energy from TiO2 host to Eu3+ ions, which was not observed in Eu(3+)-doped TiO2 nanoparticles. In comparison with direct excitation of lanthanide ions, the luminescence lifetimes of 4G5/2 of Sm3+ and 5D0 of Eu3+ were observed to be significantly prolonged upon excitation above TiO2 band-gap. A sensitization mechanism to illustrate the energy transfer from TiO2 to Sm3+ and Eu3+ was proposed based on the optical behaviors of the codoped nanoparticles. PMID- 20355560 TI - Electrospinning of polymer nanofibers with ordered patterns and architectures. AB - Nanofibers with ordered patterns and architectures are critically important for many applications, including nanoscale device fabrication and tissue regenerations. During electrospinning process, the charge on a depositing nanofiber will become constant after the volatilization of solvent complete, which happens when the nanofibers get close to a collector that usually has a certain distance from the spinneret. In this case, the component forces acting on the depositing nanofibers that are arriving to a collector surfaces can be relatively analyzed based on the simulation results of the electrical field distribution on the collector. By using finite element method (FEM), in this study, the nanofiber deposition behavior including the orientation and alignment of nanofibers that are approaching to a collector were simulated and systematically investigated in term of the effects of electrostatic field applied to the collector. Based on the simulation results, we have experimentally demonstrated that Poly(epsilon-caprolactone) (PCL) nanofibers with various desired patterns and ordered architectures were prepared using predesigned collectors. PMID- 20355561 TI - Hybrid zinc oxide nanoparticles for biophotonics. AB - A novel Zinc oxide (ZnO)-Hydrogel fluorescent colloidal semiconductor nanomaterials system is presented for potential bio-medical applications such as cell and tissue imaging. ZnO nanoparticles (NPs) synthesized using arc discharge technique has been conjugated to bio-compatible Poly N-isopropylacrylamide (PNIPAM) based hydrogel polymer matrix. The stability and fluorescence of ZnO nanoparticles are significantly enhanced using hydrogel colloidal dispersion. Photoluminescence spectroscopy indicates approximately 10 times enhancement in fluorescence in ZnO-Hydrogel colloidal system compared to ZnO-Water system, confirming the surface modification of ZnO nanoparticles by hydrogel polymer matrix. Femtosecond time resolved fluorescence measurement demonstrates that the fluorescence is due to the enhancement in absorption by the ZnO nanoparticles due to scattering by PNIPAM nanospheres. PMID- 20355562 TI - Design principles for optoelectronic applications of extraordinary light transmission effect in plasmonics nanoapertures. AB - The extraordinary light transmission effect (EOT) through sub-wavelength nanoapertures in opaque metal films has lead to observation of a wide variety of exciting new optical phenomena. This remarkable effect is generally related to the interaction of the light with the extended plasmonic resonances on the surface of the metal film and localized surface plasmons in the apertures. On the other hand, there is little conceptual understanding for controlling the localized surface plasmonic behavior of the individual apertures and their coupling to the extended surface plasmons. In this letter, we present an intuitive and straightforward picture of the extra-ordinary light transmission phenomena based on basic antenna principles for plasmonic excitations and coupling of these plasmonic excitations in complex nano-apertures. Our quasi static model remarkably well explains our experimental measurements in shape anisotropic structures with unique properties controlled by adjusting the size and the geometry of the apertures. Our approach puts forward new design principles for potential applications ranging from subwavelength optoelectronics and data storage to bio/chemical sensing. PMID- 20355563 TI - White emission via electroplex emission from two blue materials. AB - Influences of electric fields on the emission from organic light-emitting diodes (OLEDs) based on poly (N-vinylcarbazole) (PVK); 2, 9-dimethyl-4, 7-diphenyl-1, 10 phenanthroline (BCP); and tris (8-hydroxyquinoline) aluminum (Alq3) were studied. There are three emission peaks at 420 nm, 520 nm, and 620 nm of the device ITO/PEDOT: PSS/PVK/BCP/LiF/Al under different driving voltages. The emissions at 420 nm and 520 nm should be from the exciton emission of PVK and Alq3, respectively. The last emission at 620 nm could be attributed to electroplex emission at the interface between the PVK and BCP layers. A high intensity white emission via electroplex formation was obtained with Commission International d'Eclairage (CIE) coordinates (0.33, 0.34) at 15 V, which is very close to the equienergy white point (0.33, 0.33). PMID- 20355564 TI - Morphology and crystallinity of ZnS nanocolumns prepared by glancing angle deposition. AB - ZnS films with different morphologies and nanometer structures were fabricated via high vacuum electron beam deposition by changing the oblique angle alpha between the incoming particle flux and the substrate normal. The morphology and crystallinity of ZnS nanocrystalline films prepared on the substrates at alpha = 0 degrees and 80 degrees were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction. These experimental results show that the ZnS nanocolumn structure was formed at the situation of alpha = 80 degrees. The incidence angle also strongly influenced the crystallinity of thin films. The most intensive diffraction peaks changed from (220) to (111) when the incidence angle was set to 0 degrees and 80 degrees. The dynamic growth process of ZnS films at alpha = 0 degrees and 80 degrees has been analyzed by shadow effect and atomic surface diffusion. The transmittance spectra of the ZnS thin films prepared at different oblique angles were measured, and the transmissivity of ZnS nanocolumn thin films was enhanced compared with ZnS thin films prepared by normal deposition in the visible light range. PMID- 20355565 TI - Synthesis and luminescence properties of Er3+ doped Y(OH)3, NH4Y3F10, and YF3 nanocrystals. AB - Y(OH)3:Er3+ nanowires were synthesized by a hydrothermal method. Y(OH)3:Er3+ can convert into NH4Y3F10:Er3+ after fluorization, and NH4Y3F10:Er3+ can convert into YF3:Er3+ after being annealed. The structures of obtained Y(OH)3:Er3+, NH4Y3F10:Er3+, and YF3:Er3+ samples were pure hexagonal, cubic, and orthorhombic phase, respectively. Under 378-nm excitation, the three samples showed similar features. The 2H9/2, --> 4I15/2, 4F3/2(4F5/2) --> 4I15/2, and 4S3/2 --> 4I15/2 were observed, and the most intense peak was centered at 436 nm [4F3/2(4F5/2) --> 4I15/2]. Under 980-nm excitation, only the upconversion emissions from NH4Y3F10:Er3+ and YF3:Er3+ were observed. These emissions come from the following transitions: 2H11/2 --> 4I15/2, 4S3/2 --> 4I15/2, and 4F9/2 --> 4I15/2. The upconversion mechanism is discussed in detail. PMID- 20355566 TI - Magnetically responsive phase-change microspheres with large magnetization using ferrite nanoparticles. AB - Magnetically responsive phase-change microspheres were prepared and studied in this article. In the synthetic process, oleic acid was used to modify the iron oxide nanoparticles. The ferrite nanoparticles, about 10 nm in diameter, were highly dispersed due to the oleic acid on the surface of the particles, and they were encapsulated in polymethyl methacrylate (PMMA) by microemulsion polymerization with paraffin, which could be presumed from the differential scanning calorimetry (DSC) curves. According to the morphology in the scanning electron microscopy (SEM) image, the average diameter of the microspheres was about 200 nm, a large amount of nano-sized ferrite can be observed in a transmission electron microscope (TEM) image showing the structure of the microspheres. Finally, in the magnetization curve from a vibrating sample magnetometer, the saturation magnetization of microspheres was 12.2 emu/g, which was effective in the compatibility of infrared simulation and microwave absorption. PMID- 20355567 TI - Transmission through a scalar wave three-dimensional electromagnetic metamaterial and the implication for polarization control. AB - An interweaving-conductor metamaterial (ICM) is a metamaterial composed of multiple, interlocking, conducting networks. It exhibits unusual optical properties in the low-frequency linear-dispersion regime. In particular, two network ICM supports only one, non-dispersive mode in the low frequency range, and is best described as an effective medium supporting a scalar wave in full three dimensions. We explore the light transmission properties of such a metamaterial, and the implications of a scalar wave medium for polarization control. Polarizers and polarization rotators with subwavelength sizes are numerically demonstrated. PMID- 20355568 TI - Aqueous synthesis and fluorescence-imaging application of CdTe/ZnSe core/shell quantum dots with high stability and low cytotoxicity. AB - CdTe/ZnSe core/shell quantum dots were directly synthesized in an aqueous condition by heating a mixed solution of ZnCI2, NaHSe and CdTe QDs in the presence of mercaptosuccinic acid as a stabilizer. By controlling the size and composition, the CdTe/ZnSe QDs with emission wavelength ranging from 540 to 630 nm, high quantum yield (44%) and narrow full width at half maximum (FWHM) could be obtained. Characterization results with HRTEM, XRD and EDX have shown that the synthesized CdTe/ZnSe QDs have good monodispersity and a nice crystal structure, and exhibited better stability and less cytotoxicity as compared with CdTe QDs. Furthermore, luminescent QD-IgG bioprobes were produced to detect the breast cancer marker Her2 on the surface of fixed MCF-7 cancer cells for their optical imaging. PMID- 20355569 TI - Solution phase interactions controlled ordered arrangement of gold nanoparticles in dried state. AB - Gold (Au) nanoparticles (NPs) were synthesized in the presence of water soluble biomolecules such as DNA, chitosan, phospholipids, and BSA by using seed-mediated approach at room temperature. All reactions produced mostly spherical geometries with comparable size (< or = 20 nm). The NPs were arranged in a typical pearl necklace type arrangement except in the presence of BSA. Different measurements such as UV-visible, TEM, XRD, and XPS were used to characterize the Au NPs. Fluorescence spectroscopy was used to identify the interactions between biomolecules and blank (uncapped) Au NPs in aqueous colloidal solutions. It was concluded that the favorable interactions between Au NPs and biomolecules in aqueous phase, in fact, drive them into pearl-necklace type arrangement in the dried state. PMID- 20355570 TI - Room temperature surfactant assisted crystal growth of silver nanoparticles to nanoribbons. AB - This study presents a simple and systematic growth of Ag nanoparticles (NPs) to nanoribbons by changing the hydrophobicity parameter of a series of cationic Gemini surfactants by using seed-mediated approach in aqueous phase at room temperature. At lowest hydrophobicity of a Gemini surfactant (i.e., dimethylene bis(decyldimethyl-ammonium bromide), 10-2-10), Ostwald ripening process was observed which caused fusion among growing Ag NPs. This process was quite prominent when 0.5 ml of Ag seed solution was used for the growth process but weakened as the amount of seed decreased to 0.125 ml. Similar behavior was demonstrated by Au NPs studied for comparison. The nanostructures were characterized by TEM, XRD, and UV-visible measurements. Further increase in the hydrophobicity of a Gemini surfactant from 10-2-10 to dimethylene bis(tetradecyldimethylammonium bromide) (14-2-14) through dimethylene bis(dodecyldimethylammonium bromide) (12-2-12), resulted in the participation of threads like micelles and liquid crystalline phase as soft-templates towards the nanoribbon formation. Fine polycrystalline Ag nanoribbons were obtained in the presence 14-2-14 and were characterized by the HRTEM and EDX analysis. PMID- 20355571 TI - Modified effective dielectric function for metallic granular composites with high percolation threshold. AB - We propose the effective dielectric function theory of metal granular composites modified with the metal particle size. The modified theory is used to explain the electrical conductivity, resonant plasmon absorption, and large nonlinear absorption of Au-TiO2 granular composite films with high-density metallic particles and a high electric percolation threshold. It is revealed that the decreasing metal particle size leads to an increasing percolation threshold and large enhancement of optical nonlinearity of the composites. PMID- 20355572 TI - Gold nanoshell assembly on a ferritin protein employed as a bio-template. AB - Gold nanoshells around 26 nm in diameter with a 7 nm thick wall were fabricated in an aqueous solution using pre-reconstituted ferritin proteins as a removable bio-template. The synthesis of gold nanoshells was initiated by planting gold nanoparticle seeds in the hydrophilic three-fold channels of the ferritin protein. The process was facilitated by the energetically favorable gold-sulfur bonds formed at the cysteine residues lining these channels. PMID- 20355573 TI - Synthesis of ordered macroporous polymers from colloidal silica templates. AB - Ordered macroporous polymers have been prepared by replication of colloidal crystals made from silica spheres 298 nm in diameter. The colloidal crystals were prepared on a clean indium tin oxide (ITO) glass substrate by sedimentation of a solution of a silica colloidal dispersed solution. The air between the silica spheres was filled by the monomer of poly(methyl methacrylate) (PMMA) that can be subsequently polymerized. After infiltration, the silica spheres were removed by means of etching with hydrofluoric acid (HF) aqueous solution and left a polycrystalline network of interconnected pores. These macroporous ordered structures represent a promising approach for bandgap engineering and can be used as the foundation of various potential applications. PMID- 20355574 TI - Synthesis and spectral characterization of EuPO4 and LaPO4:Eu nanorods. AB - Monoclinic monazite-type EuPO4 and LaPO4:Eu nanorods were synthesized by a microemulsion-assisted solvothermal method. Their morphologies, structures, and fluorescent properties were characterized by SEM, XRD, and photoluminescence (PL) modern analytic means, respectively. The aspect ratios of EuPO4 and LaPO4:Eu nanorods have a decreasing tendency with increasing carbon chain length of assisted surfactants. When the assisted surfactant was n-butyl alcohol, the EuPO4 exhibited nanorod morphology with diameters from 20 to 30 nm and lengths from 100 to 150 nm. When the assisted surfactant was n-pentanol, the EuPO4 nanorods had lengths between 200 and 300 nm and a diameter range similar to that of the n butyl alcohol nanorods. When the assisted surfactant was n-hexanol and n-octyl alcohol, only elliptical EuPO4 products were obtained. The LaPO4:Eu nanorods synthesized in the presence of different assisted-surfactants exhibited elliptical morphologies with diameters of 40-60 nm and lengths of 70-110 nm. The LaPO4:Eu and EuPO4 nanorods showed a orange prominent emission peak from magnetic dipole transition 5D0 --> F1 (593 nm) of Eu3+ ions whose sites in the EuPO4 and LaPO4:Eu nanorods have C1 symmetry. Compared with bulk LaPO4:Eu, the fine structure of the Eu-O charge transfer band has very small red shift resulting from the slight increase of the length of Eu-O bond due to nanoscale size effect. PMID- 20355575 TI - Synthesis and optical properties of Bi3+ doped NaTaO3 nano-size photocatalysts. AB - Well-crystallized NaTaO3 nanoparticles doped with and without Bi were synthesized by a hydrothermal method. X-ray diffraction (XRD) patterns showed a systematic shift toward lower angles, which was followed by broadened peaks as the dopant content of Bi3+ increased. The doping of Bi3+ in NaTaO3 was also found to give rise to finer particle sizes. For undoped samples, transmission electron microscopy (TEM) showed the well-crystallized cubic morphology, which however, changed to fairly rough surfaces and somewhat irregular distorted cube-like shaped geometries with the addition of Bi3+. The swelling of the crystallized cell volume was demonstrated by the increased lattice d-spacing from high resolution transmission electron microscopy (HRTEM) studies. The diffuse reflection spectra showed a red shift in absorbance wavelength with Bi3+ doping, which suggests a decreased band gap energy. Emissions of the TaO6 octahedra unit were observed at 435 nm in the photoluminescence (PL) spectra. The PL intensities increased with the doping content of Bi3+, which was attributed to the increase of oxygen vacancies caused by the substitution of Ta5+ by Bi3+. The photocatalytic degradation of methylenebluechloride was taken as the model reaction to examine the activity of the sample. It was found that the activity decreased with the Bi3+ content. PMID- 20355576 TI - Hydrothermal synthesis and photoluminescent properties of YBO3:Eu3+ nanophosphor under ultraviolet and vacuum ultraviolet excitation. AB - YBO3:Eu3+ Nanophosphors were prepared by hydrothermal reaction (HR) with different reaction times. When the reaction times increased, the grain sizes of phosphor did not change obviously, but the particle size, morphology, and aggregation state were different. This transformation has influenced luminescent properties. The change trends of luminescent intensity under ultraviolet (UV) and vacuum ultraviolet (VUV) excitation are almost contrary: the nanophosphor that has better intensity in UV region is lower in the VUV region and vice versa. The emission under UV excitation decreases first and increases later as time increases. However, the emission under VUV excitation increases first and decreases later. In the UV region, orange emissions (at 592 nm) are higher than red emissions (at 611 nm), but in VUV regions, red emissions are higher. All results indicated that luminescence properties of nanophosphors in VUV regions differ greatly from those of nanophosphors in UV regions. In a certain nanoscale, the decreased particle size will lead to enhanced luminescence under VUV excitation but weaker luminescence under UV excitation. The related phenomena and possible explanations are also discussed. PMID- 20355577 TI - Phase evolution and photoluminescence of Eu(3+)-doped ZrO2. AB - Eu3+ doped ZrO2 nanocrystals were prepared by decanoic acid-assisted hydrothermal method. X-ray diffraction, transmission electron microscope, Fourier transform infrared spectroscopy, Ultraviolet-visible diffuse reflection spectroscopy, and photoluminescence spectra were used to characterize the phase evolution, morphology, surface species, and optical properties of the samples. At low Eu3+ content, monoclinic ZrO2 was achieved to show a rod-like morphology. With increasing the Eu3+ content, tetragonal ZrO2 nanocrystals were obtained to show a ball-like shape. Decanoic acid molecules were decorated on the surfaces of ZrO2 nanocrystals, which gave rise to a typical absorption centered at 300 nm. In addition to the characteristic emission of Eu3+, an intense broad emission was detected for pure and Eu(3+)-doped ZrO2 nanocrystals under ultraviolet excitation, which is interpreted in terms of the F/F+ and/or AOD+ centers that are related with the oxygen vacancies. PMID- 20355578 TI - Selective microwave absorption of iron-rich carbon nanotube composites. AB - We report on high selectivity of microwave absorption by controlling the concentration of carbon nanotubes in polymer composites and matching the dielectric loss and magnetic loss through encapsulation of crystalline Fe nanorods inside nanotubes. The reflection loss reached more than 10 dB (> 90% absorption) by loading nanotubes at concentrations of 1 wt% to 10 wt% into the composites, and the frequencies corresponding to the maximum loss can be tailored throughout the range of 2 to 18 GHz by changing the concentration. A maximum absorption capability (75 dB x GHz) was observed at a CNT loading of about 4.5 wt%. The crystalline structure of encapsulated Fe nanorods can be modified to enhance the reflection loss. Control of absorption selectivity by modifying the structure and concentration of nanoscale fillers could facilitate potential higher-frequency applications (e.g., radar absorbing) of nanocomposites. PMID- 20355579 TI - Entanglement generation using silicon photonic wire waveguide. AB - This paper reviews recent progress on telecom-band entangled photon-pair sources based on spontaneous four-wave mixing (SFWM) in a silicon photonic wire waveguide. Thanks to the large third order nonlinearity of nano-scale silicon waveguides, we can generate photon pairs efficiently. Moreover, the use of silicon waveguides enable us to avoid the noise photons caused by spontaneous Raman scattering, which has been a serious problem with entanglement sources based on SFWM in dispersion shifted fiber. We successfully demonstrated high purity time-bin and polarization entanglement generation using 1-cm long silicon waveguides. PMID- 20355580 TI - Optical response of CdSe quantum dots to cesium-137 gamma-ray radiation. AB - The optical response of colloidal photoluminescent (PL) semiconductor nanocrystals to 137Cs gamma radiation was investigated. The quantum dots (QDs) used were CdSe dispersed in hexane, exhibiting bandgap absorption and emission peaking at 556 nm and 563 nm, respectively. The doses of the 137Cs gamma radiations were 0.1, 1.0, 10 and 100 Gy with a dose rate of 0.805 Gy/min. Each radiation was performed on two identical samples; right after the radiation, absorption and emission measurements were performed. The change of the optical properties after the radiation was presented together with those of a control sample without radiation exposure. The prompt absorption measurements showed that there is little change with the 0.1 Gy up to 100 Gy radiations, while the prompt emission measurements showed that with the 0.1 Gy and 1 Gy radiation, there is a negligible change in the PL intensity; with the 10 Gy and 100 Gy radiation, there is a noticeable decrease in the PL intensity. Therefore, it seems that the radiation does not destroy the QDs themselves but leads to some loss of their surface passivation. Furthermore, the optical properties of the eight irradiated samples and the control sample were monitored periodically up to days. Interestingly, after the storage of days in dark, there is significant recovery in the PL intensity of the large-dose irradiated samples; such a rebound tendency provides the potential for the colloidal QDs to be novel and promising candidates in radiation dosimeter with multi-detection capability. PMID- 20355581 TI - Bright green upconversion fluorescence of Yb3+, Er(3+)-codoped NaYF4 nanocrystals. AB - Uniform hexagonal NaYF4: Yb3+, Er3+ nanocrystals (NCs) with bright green upconversion fluorescence were prepared. The nanocrystals were highly hydrophobic and dispersed in cyclohexane forming a transparent colloidal solution due to the use of oleic acid as a capping ligand. Temperature dependence for emission of Er3+ ions in this sample was also studied. The green emission intensity of Er3+ ions had a maximum at 160 K under 980 nm excitation, which was attributed to the thermally activated distribution of electrons and the thermal quenching effect. The transparent colloidal solution is expected to be a good candidate for research in biological imaging or display applications. PMID- 20355582 TI - Preparation of optically anisotropic nanocomposites with oriented gold nanorods embedded in polyvinyl alcohol. AB - We demonstrated a simple but general method to prepare large-area flexible nanocomposites with oriented gold nanorods (GNRs) embedded in polyvinyl alcohol (PVA) film by directly introducing a GNR colloidal solution into a PVA aqueous solution and using solid-state drawing techniques. The optical property of the nanocomposite exhibits a strong dependence on the angle between the polarization of the incident light and the drawing direction of the nanocomposite film. The color of the composite film can be intelligently tuned and displays red and blue when the light polarization is switched parallel to and perpendicular to the drawing direction, respectively. These composite films have promise for application in a single electrooptical device. PMID- 20355583 TI - Luminescence and energy transfer of organic chromophores bound to inorganic nano lamellar frameworks. AB - Fluorescein, an organic chromophore with high fluorescence quantum yield, was bound to a cetyltrimethylammonium zirconium phosphate nano-lamellar framework and its luminescence properties and energy transfer from fluorescein to porphyrins were characterized. Upon the incorporation of fluorescein chromophore within the layered materials, not only was the interlayer distance of the framework adjusted from 39.6 to 24.7 angstroms, but also the luminescence properties of fluorescein were dramatically changed. The excitation maximum was red-shifted from 488 to 500 nm, and the emission peak was red-shifted from 510 to 525 nm. These results implied the formation of chromophore/framework hybrid assemblies. After fluorescein and tetra(p-methoxphenyl)porphine chromophores bound to the framework together, obvious energy transfer was observed, resulting in more effective fluorescence efficiency for the porphyrins. Without the framework, such energy transfer was absent in the same chromophore concentrations in aqueous solutions. Due to the unique microenvironments provided by the inorganic lamellar framework, the electronic interactions of the chromophores were tuned. Therefore, their emission properties were changed, and the energy transfer processes were promoted. PMID- 20355584 TI - Growth of highly oriented ZnO nanowires on GaN substrates for electronic and optical sensor applications. AB - In this Paper we present growth and characterization results of highly oriented ZnO nanowires grown on wide bandgap GaN substrates. Experimental results on the ZnO nanowires grown on p-GaN are presented with growth morphology and dimensionality control. We also present experimental results on these nanowire arrays such as I-V measurements and UV sensitivity measurements. The ZnO nanowires can be used for a variety of nanoscale optical and electronics applications. PMID- 20355585 TI - Synthesis and optical properties of vertically aligned ZnO nanorods. AB - ZnO nanorods were grown on an n-type silicon (111) substrate with the assistance of Au catalyst by chemical vapor deposition (CVD). The ZnO nanorods were about 200 nm diameter with uniform lengths of about 1.2 microm. The ZnO nanorods exhibited [0001] orientation. ZnO nanorods grow in dense arrays perpendicular to the (111)-plane of silicon due to [0001]ZnO perpendicular [111]Si, [2110]ZnO perpendicular [110]Si, [1210]ZnO perpendicular [101]Si and [1120]ZnO perpendicular [011]Si epitaxy. Room-temperature photoluminescence (PL) measurements show three near band-edge emission peak at 377, 379, 389 nm. These peaks are attributed to exciton transitions. Analysis indicates that the band gap of ZnO nanorods is 3.301 eV and exciton binding energy is 0.114 eV. PMID- 20355586 TI - A facile approach to synthesize alumina nanostructures at room temperature. AB - Alumina nanostructures, nanowires, and semicolumn nanotubes with high aspect ratios were synthesized by the chemical etching of porous alumina membranes (PAMs) in phosphoric acid solution. The morphology and structure of alumina nanostructures were analyzed by scanning electron microscopy (SEM), energy dispersive spectrum (EDS), and X-ray diffraction (XRD), respectively. The results showed that the typical features of highly flexible nanostructures were around 20 40 nm in diameter and around 100 microm in length. EDS analysis indicated that the nanostructures were constructed by aluminum oxide. The crystalline structure of the alumina nanostructures was amorphous, which was in accordance with that of the PAMs. Furthermore, the morphology of the PAMs was characterized in detail by atomic force microscope (AFM) and SEM. On the basis of AFM and SEM observations, a possible formation mechanism of alumina nanostructures was discussed, and the inhomogeneous dissolution between the triple points and the side walls was considered to be the essential factor deciding the formation of nanostructures. PMID- 20355587 TI - Characteristics of nickel doped zinc oxide thin films prepared by sputtering. AB - Nickel-doped zinc oxide thin films were prepared by the magnetron sputtering method. We have studied the structure and optical properties of the samples by using X-ray diffraction (XRD), scanning electron microscopy (SEM), and optical transmittance. The chemical ingredients were examined by energy dispersive X-ray spectroscopy (EDS), and the charge state of Ni ions in the ZnO:Ni films was characterized by X-ray photoelectronic spectrometry (XPS). From the XRD spectra of the samples, it was obvious that there was no second phase, but the doping can disturb the ZnO crystal lattice and change the lattice parameters. All the films prepared have a wurtzite structure and grow mainly along the c-axis orientation. The magnetic measurments showed that the samples exhibit no ferromagnetism above room temperature. PMID- 20355588 TI - Electronic structure and linear optical properties of ZnSe and ZnSe:Mn. AB - As an important wide band-gap II-VI semiconductor, ZnSe has attracted much attention for its various applications in photo-electronic devices such as blue light-emitting diodes and blue-green diode lasers. Mn-doped ZnSe is an excellent quantum dot material. The electronic structures of the sphalerite ZnSe and ZnSe:Mn were calculated using the Vienna ab initio Simulation Package with ultra soft pseudo potentials and Material Studio. The calculated equilibrium lattice constants agree well with the experimental values. Using the optimized equilibrium lattice constants, the densities of states and energy band structures were further calculated. By analyzing the partial densities of states, the contributions of different electron states in different atoms were estimated. The p states of Zn mostly contribute to the top of the valence band, and the s states of Zn and the s states of Se have major effects on the bottom of the conduction band. The calculated results of ZnSe:Mn show the band gap was changed from 2.48 to 1.1 eV. The calculated linear optical properties, such as refractive index and absorption spectrum, are in good agreement with experimental values. PMID- 20355589 TI - Upconversion luminescence properties of Er(3+)-Bi3+ codoped CaSnO3 nanocrystals with perovskite structure. AB - New phosphor nanocrystals of ASnO3:Er3+ (A = Ca, Sr, and Ba) and CaSnO3:Er(3+) Bi3+ were prepared by a hydrothermal method. Their structures were examined by X ray diffraction and Raman spectroscopy. Upconversion luminescence properties of the Er3+ ions in these host materials were investigated upon excitation at 980 nm. Green emission bands of Er3+ around 528 and 545 nm were more favorable in CaSnO3 than in SrSnO3 and BaSnO3. This was interpreted in terms of a crystal structural distortion and configuration coordinate model. The investigation of the upconversion luminescence of Er(3+)-Bi3+codoped CaSnO3 nanocrystals indicates that Bi3+ ions could largely sensitize the emission of Er3+ ions which was attributed to the efficient energy transfer from Bi3+ to Er3+ ions and the modification of the local symmetry of Er3+ ions. The results show that the CaSnO3:Er(3+)-Bi3+ nanocrystals have potential application for fabricating visible upconversion devices. PMID- 20355590 TI - Valence-change of Eu and its effects on the luminescent properties of Sr2MgSi2O7:Eu,Dy. AB - Long afterglow phosphors of Sr2MgSi2O7:Eu,Dy were prepared by high temperature solid state reaction in oxidation atmospheres, and then were treated sequentially in reducing atmosphere --> oxidation atmosphere --> reducing atmosphere. The crystal structure of the samples was investigated by using powder X-ray diffraction (XRD). The measurements of the photoluminescence and the thermoluminescence properties suggest the difference in the luminescent properties between Eu2+ and Eu3+. Eu3+ ions occupy two different sites, and their emission spectra consist of four discrete line spectra, due to the 5D0 --> 7F1 (590 nm), 5D0 --> 7F2 (618 nm), 5D0 --> 7F4 (703 nm) and the 5D2 --> 7F3 (510 nm) transitions. But in contrast, the emission spectrum of Eu2+ is characteristic of a broadband spectrum due to the 4f(7) --> 4f(6) 5d(1) transition. The luminescence of Sr2MgSi2O7:Eu2+,Dy3+ displays both higher intensity and longer decay than that of Sr2MgSi2O7:Eu3+,Dy3+. The emissions from Dy3+ are detected in all samples, indicating that Dy3+ ions act not only the trap center but also the luminescence center in the host lattice of Sr2MgSi2O7. PMID- 20355591 TI - Optical properties of Nd3+ ion-doped ZnO nanocrystals. AB - Hexagonal Nd(3+)-doped ZnO nanocrystals with multiple luminescent centers were synthesized by means of a facile sol-gel method. The Nd(3+)-doped ZnO nanocrystals were characterized by using the X-ray diffraction, transmission electron microscopy, ultraviolet-visible reflectance spectra, and fluorescence spectroscopy. Host-to-Nd3+ energy transfer was observed for the first time in Nd(3+)-doped ZnO nanocrystals. It was found that Nd3+ ions can be effectively sensitized by the ZnO nanocrystals, resulting in sharp and intense characteristic Nd3+ luminescence. The photoluminescence (PL) and PL excitation spectra of Nd3+ ions in the ZnO nanocrystals were investigated in detail. Furthermore, the possible mechanism of host-to-Nd3+ energy transfer was also proposed on the basis of the optical properties of Nd3+ ions in the ZnO nanocrystals. PMID- 20355592 TI - Multicolor light emission of GdVO4:Ln3+ nanorods by a single-wavelength excitation. AB - Highly dispersed Ln(3+)-doped GdVO4 nanorods were prepared via a hydrothermal method with the assistance of EDTA and CTAB. By systematic structural and property characterization using X-ray diffraction, transition electron microscope, selected area electron diffraction, infrared spectra, and photoluminescence, it is indicated that the as-prepared GdVO4 nanocrystals showed a rod-like shape with an average diameter of about 7 nm and length of 30-50 nm. Under a single-wavelength excitation at 320 nm, GdVO4 nanocrystals doped with Dy3+, Sm3+, and Eu3+ gave surprising multicolor emissions in the visible region, while no blue component at 430 nm from un-doped GdVO4 nanocrystals was seen. This observation was interpreted in terms of the effective energy transfer process between [V4+]A center and lanthanide ions. PMID- 20355593 TI - Electrical characterization of a single electrospun porous nanostructured tin oxide ribbon. AB - A single nanostructured porous tin oxide ribbon, with its length, width and thickness of more than 1 mm, around 20 microm and around 20 nm, respectively, were fabricated using electrospinning, and electrically characterized in a temperature range between 300 K and 90 K, a magnetic field range from -9 to 9 T (negative sign stands for the reverse direction), and the environment of air and vacuum. The electrical conductivity (sigma) of the ribbon was found insensitive to magnetic field, but sensitive to temperature and environment. Its response time to air evacuation is 67+7 s. The strong temperature dependence of sigma in vacuum is controlled by the three-dimension variable-range hopping of localized electrons. PMID- 20355594 TI - Observation of the first excited state of A-exciton in ZnO nanocombs. AB - High-quality ZnO nanocombs were synthesized on Si substrates coated with Au films by evaporating ZnO powders with a high yield. The morphology of the ZnO nanocombs was characterized by scanning electronic microscopy. In order to study the dynamic process of near-band edge emission, the temperature-dependent photoluminescence spectra were measured. The first excited state emission of A free exciton centered at 3.403 eV was observed at 87 K. PMID- 20355595 TI - Effect of surface-absorbing chemical groups on the luminescence of Yb3+/Er3+ co doped nanosized Y2O3. AB - Er3+/Yb3+ co-doped nanocrystal Y2O3 powders with different sizes were prepared by using a chemical auto-combustion reaction. X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were used to characterize the crystal structure and morphology of the samples. Fourier transform infrared (FT-IR) spectra showed that the surfaces of smaller particles absorbed a larger amount of NO3-, CO3(2-) and OH- groups. These chemical groups caused an increase of the population ratios of the 4I13/2 level to the 4I11/2 level when the particle size decreased, thus resulting in a change of the red green upconversion emission intensity ratio under 980 nm excitation. The 1.5 microm emission intensity also changed with the particle size. These results suggest that surface status is an important factor influencing the luminescent properties of nano-sized materials and that surface modification is needed in order to obtain the satisfied materials. PMID- 20355596 TI - Study on upconversion luminescence and luminescent dynamics of 20%Yb3+, 0.5%Tm3+ co-doped YF3 and GdF3 nanocrystals. AB - 20%Yb3+, 0.5%Tm3+ co-doped YF3 and GdF3 were synthesized through a facile hydrothermal method. After annealing under an argon atmosphere, the sizes and morphologies of the two samples were characterized by field emission scanning electron microscopy, and the phase and crystallization were analyzed by X-ray diffraction. With a 980 nm continuous wave laser diode as the excitation source, blue and ultraviolet upconversion emissions in the wavelength range of 260-510 nm of Tm3+ and Gd3+/Tm3+ ions were recorded. Under the same excitation conditions, the upconversion emission spectra of the two nanocrystals were compared and analyzed. Gd3+ in the ground state cannot absorb 980 nm photons directly because of the large energy gap between the ground state 8S7/2 and the first excited state 6P7/2. In the 20%Yb3+, 0.5%Tm3+ co-doped GdF3 nanocrystals, the excited states 6I(J) of Gd3+ can be populated through the energy transfer 3P2 --> 3H6 (Tm3+): 8S7/2 --> 6I(J)(Gd3+), meaning that Yb3+ acted as primary sensitizers and Tm3+ acted as secondary sensitizers, transferred energies to host material Gd3+ and resulted in the ultraviolet upconversion emission of the host ions. In this article, the upconversion luminescent dynamics were studied at the onset of a 980 nm pulsed laser from an optical parametric oscillator pumped by a 10 ns pulsed Nd:YAG laser, too. PMID- 20355597 TI - Preparation and research of nano-scale europium (III)-pyromellitic acid powder luminescent material. AB - The nanoscale luminescent complex of europium (III)-pyromellitic acid was synthesized successfully in the polyvinylpyrrolidone (PVP) matrix by a co precipitation method. The chemical formula of the synthesized complex was speculated to be PVP/Eu4/3L x 3H2O by elemental analysis, inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and Fourier-transform infrared spectroscopy (FT-IR). The X-ray diffraction (XRD) pattern of PVP/Eu4/3L x 3H2O indicated that it was a new crystalline complex since the diffraction angle, diffraction intensity, and distance of the crystal plane were all different from those of the ligand. It is proved by the thermogravimetric curve that the synthesized nanoscale luminescent complex was stable, ranging from ambient temperature to 479 degrees C in air. The transmission electron microscopy (TEM) image showed that the complex was nanoparticles. The synthesized complex emitted the characteristic red fluorescence of Eu(III) ions under ultraviolet excitation by the photoluminescence analyses. For example, the emission peaks of PVP/Eu4/3L x 3H2O at 578, 591, 612, and 694 nm using 322 nm as exciting wavelength are assigned to the 5D0 --> 7F0, 5D0 --> 7F1, 5D0 --> F2, and 5D0 --> 7F4 electron transitions of the Eu3+ ions, respectively. PMID- 20355598 TI - Influence of crystal structure on the fluorescence emission of Eu3+:LaOF nanocrystals. AB - Optical transitions of Eu(3+)-doped LaOF nanocrystals with tetragonal and rhombohedral structures were studied experimentally using laser spectroscopic method. Fluorescence emissions from 5D1 and 5D0 of Eu3+ in LaOF nanocrystals were detected by exciting the sample with a 532 nm pulsed laser, and the influence of local symmetry on the fluorescence emission of doped ions was observed. The specific crystalline phase as well as the local symmetry on the fluorescence emission was investigated in both the frequency domain and time domain. It was found that Eu3+ ions doped in the tetragonal crystal structure present more efficient fluorescence emission, which was explained by lower symmetric distribution of local field at the doped ions. PMID- 20355599 TI - Ionic liquid-based approach to monodisperse luminescent LaF3:Ce,Tb nanodiskettes: synthesis, structural and photoluminescent properties. AB - In this paper, a novel and easy synthesis of highly luminescent, water-soluble LaF3:Ce,Tb nanodiskettes (25 nm in diameter) by ionic liquid-based hydrothermal process is reported. X-ray diffraction (XRD), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) were used to characterize the structural properties of the LaF3:Ce,Tb nanodiskettes. Ionic liquid [bmim]BF4 acts as both a co-solvent and a reactant during the synthesis. The effects of EDTA-2Na on the formation of green LaF3:Ce,Tb nanodiskette phosphors were studied and discussed. The luminescent properties of LaF3:Ce,Tb nanodiskettes have been investigated under 254 nm excitation both in solid state and dispersed in solution. The quantum efficiency (in solid state) is about 20% compared with commercial green phosphor. The photoluminescent properties show that the as-prepared La0.8Ce0.15Tb0.05F3 nanodiskettes may be applied as phosphors for high-resolution displays and fluorescent labels for biomolecules. PMID- 20355600 TI - Upconversion luminescence properties of Yb3+, Gd3+, and Tm3+ co-doped NaYF4 microcrystals synthesized by the hydrothermal method. AB - Yb3+/Gd3+/Tm3+ co-doped prism-like NaYF4 microcrystals were synthesized through a facile ethylene diamine triacetic acid (EDTA)-assisted hydrothermal method. The microcrystals were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), upconversion (UC) emission spectra, and decay curve. After annealing in an argon atmosphere, the microcrystals emitted bright blue and intense ultraviolet (UV) light under a 980-nm continuous wave diode laser excitation. Besides the UC emissions of the Tm3+ ions, 6D(J), 6I(J) and 6P(J) --> 8S7/2 UC emissions of Gd3+ were observed. During the emission process of Gd3+ ions, both Yb3+ and Tm3+ ions served as sensitizers. In the complex excitation and frequency UC processes, excited state absorption of Gd3+ ions, cross relaxation energy transfer (CRET) between two excited Gd3+ ions, and energy transfer (ET) between Gd3+ and Yb3+ or Tm3+ ions played key roles for the UC emissions of Gd3+ ions. PMID- 20355601 TI - Fabrication and luminescence properties of Nd3+:Y2O3 transparent ceramics. AB - Y2O3 nanoparticles doped with different concentrations of Nd3+ were prepared by the coprecipitation method, and the Nd3+:Y2O3 transparent ceramics were fabricated by vacuum sintering at 1700 degrees C, under 1 x 10(-3) Pa for 6 h. The structural, morphological, and luminescence properties of the samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and fluorescence analysis. The results show that the Nd3+:Y2O3 nanoparticles are homogeneous in size and nearly spherical, and the average diameter of the particles is in the range of 40-60 nm. There are no other phases except the Y2O3 cubic phase in the Nd3+:Y2O3 nanoparticles and transparent ceramics. Nd3+ dissolves completely in the Y2O3 cubic phase. The relative density of Nd3+:Y2O3 transparent ceramics is 99.7%, and the transmittance of the Nd3+:Y2O3 transparent ceramics exceeds 80% at the wavelength range. PMID- 20355602 TI - The electrodeposition of zinc oxide two-dimensional nanomesh and three dimensional inverse opal complex connected structures. AB - The fabrication of the periodic ordered structures with complex shapes or heterostructures are important for many potential applications. In this paper, zinc oxide two-dimensional (2D) nanomesh and three-dimensional (3D) inverse opal complex connected structures were fabricated by the electrochemical deposition method. 2D ZnO nanosheets or sheet-like porous structures standing on the 3D ZnO inverse opals were synthesized. Two different methods: the co-deposition method and the two-step deposition method were employed for the preparation of the complex structures. The deposition process of complex structures is discussed. The photonic band gap of the complex macroporous structure was calculated using the Translight software and characterized by the micro-region reflection and transmission spectra. The exciton luminescence of ZnO can be inhibited by the inverse opal structure when the photonic band gap superposes with the luminescent band. PMID- 20355603 TI - Buffer layer of PEDOT:PSS/graphene composite for polymer solar cells. AB - High-efficiency polymer solar cells were made with a hydrophilic graphene oxide (GO) doped in poly(ethylene dioxythiophene) (PEDOT)-polystyrene sulfonic acid (PSS) composites using a structure of indium tin oxide/PEDOT:PSS:GO (40 nm)/poly(3-hexylthiophene-1,3-diyl) (P3HT)-[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) (1:0.6, 100 nm)/LiF (1 nm)/Al (70 nm). The energy conversion efficiency eta was enhanced from 2.1 to 3.8% by doping GO into the PEDOT:PSS buffer layer under AM1.5G 100 mW cm(-2) illumination in air. The pre-annealing of GO makes energy conversion efficiency 1.8 times that of the device based on a pristine PEDOT:PSS buffer layer. Because of the low price and ease of preparation, soluble graphene will be a promising buffer layer used in photovoltaic applications. Furthermore, it can be used in other electronic applications. PMID- 20355604 TI - Synthesis and luminescence properties of YF3:Ce3+/Tb3+ nanocrystals. AB - YF3:Ce3+, YF3:Tb3+, and YF3:Ce3+/Tb3+ nanocrystals were synthesized by an ethylenediaminetetraacetic acid (EDTA)-assisted hydrothermal method and characterized by X-ray diffraction and scanning electron microscope. In the excitation spectra, there is one broad excitation band at 285 nm for YF3:Ce3+ and 255 nm for YF3:Tb3+, which are related to the f-d excitations of the Ce3+ and Tb3+ in the host, respectively. In the emission spectra of YF3:Ce3+/Tb3+ nanocrystals under different excitation wavelengths (285 and 255 nm), both spectra exhibit the emissions of Ce3+ and Tb3+, indicating that energy transfer could take place not only from Ce3+ to Tb3+ but also from Tb3+ to Ce3+ ions. PMID- 20355605 TI - Co-precipitation synthesis and characterization of Bi3+, Eu3+ co-doped nanocrystal Gd2WO6 phosphors. AB - Eu3+ single-doped and Bi3+/Eu3+ co-doped nanocrystal Gd2WO6 phosphors were successfully synthesized via a co-precipitation reaction. The structure and morphology of the phosphors were characterized by using X-ray powder diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). The influence of Bi(3+)-doping concentration on the excitation and emission spectra was studied. It was found that the introduction of Bi3+ can greatly affect the charge transfer band and the luminescence intensity of Eu3+ but does not cause a change in the profile of emission spectra of Eu3+. PMID- 20355606 TI - Demonstration of optical gain at 1550 nm in erbium-ytterbium co-doped polymer waveguide amplifier. AB - A novel solution-processable erbium-ytterbium co-doped complex was successfully synthesized and used to fabricate a waveguide amplifier. The absorption and photoluminescence spectra of the complex were observed. The full width at half maximum (FWHM) was about 80 nm. An embedded waveguide structure was fabricated using the complex as the core layer and SU-8 material as the cladding layers. With an input signal power of 0.2 mW and pump power of 133.6 mW, an optical gain of 4.14 dB at a wavelength of 1550 nm was obtained in a 29 mm-long waveguide. PMID- 20355607 TI - The synthesis of beta-SiC nanoparticles by high-energy mechanical ball milling and their photoluminescence properties. AB - We succeeded in the synthesis of single-phase beta-SiC nanoparticles via simple and low-cost high-energy mechanical ball milling of a silicon and graphite mixture at ambient temperature. The synthesis products were characterized by X ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and selected area electron diffraction (SAED). The results show that starting graphite and silicon mixture reacted completely into beta-SiC nanoparticles with an average grain size of approximately 8 nm after being milled for 20 h, and the grain size gradually decreased as milling time increased from 20 to 60 h but remained basically unchanged above 60 h. The agglomeration problem of the beta-SiC nanoparticles synthesized by ball milling was resolved to a great extent by the introduction of 2 wt% NH4Cl to the initial Si-C mixture. Under 325 nm excitation, a stable and intensive broad emission peak at 387 nm was observed in the photoluminescence (PL) spectrum of the synthetic nanoparticles, and this emission shows an obvious blueshift of bandgap. PMID- 20355608 TI - Synthesis of dual fluorescent encoding magnetic composite nanoparticles. AB - A new class of high stable, dual fluorescent encoding magnetic composite nanoparticle has been synthesized via reverse microemulsion method. Two kinds of CdTe QDs with different emission wavelengths and magnetic nanoparticles (Fe3O4) were embedded in silica nanoparticles at precisely controlled ratios. In this process, superparamagnetic Fe3O4 nanoparticles and one kind of QDs (573 nm) as cores were coated with silica, forming the first core-shell structure magnetic fluorescent nanoparticles (MFNs); then the MFNs and the other kind of QDs (653 nm) as cores were coated with another silica shell to form the fluorescent, magnetic dual core-shell encoding composite nanoparticles. With the aim of embedding more QDs in MFNs, we use poly(dimethyldiallyl ammonium chloride) to balance the electrostatic repulsion between QDs and silica intermediates. A surface-active reagent, 3-aminopropyltrimethoxysliane was used to link the MFNs with QDs and terminate the surface of composite nanoparticles. Finally, by modifying the surface of composite nanoparticles with amino groups and methylphosphonate groups, biologically functionalized and monodispersed composite nanoparticles were obtained. PMID- 20355609 TI - Large-scale synthesis and photoluminescence properties of aligned multicore SiC SiO2 nanocables. AB - By using a simple and low-cost microwave method, aligned multicore SiC-SiO2 nanocables have been successfully synthesized on a large scale. The composition and structural features of the products were characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The results revealed that each of the nanocables was composed of several 3C-SiC nanowires encapsulated in a single amorphous SiO2 shell. The cores were 10-50 nm in diameter and up to hundreds of microns in length. The photoluminescence properties of the nanocables were studied, and strong violet blue light emission was observed at wavelengths of about 339 and 390 nm under 325-nm excitation. The origin of the photoluminescence from the nanocables can be attributed to the central SiC nanowires and defects in silicon oxide or the SiC/SiO2 interface boundary. Based on experimental characterizations, an oxide-assisted vapor-liquid solid (VLS) growth mechanism was used to elucidate the growth process of the multicore SiC-SiO2 nanocables. PMID- 20355610 TI - Adjustable up-conversion luminescence color in rare earth co-doped transparent oxyfluoride nano-glass-ceramics. AB - Transparent oxyfluoride nano-glass-ceramics with highly efficient up-conversion and adjustable color luminescence were developed in the 28SiO2 x 17Al2O3 28PbF2 x 22CdF2 x 0.1NdF3 x xYbF3 x yHoF3 zTmF3 x (4.9 - x - y - z)GdF3 composition, in mol%. X-ray diffraction and transmission electron microscopy measurements revealed that heat treatments of the oxyfluoride glasses cause the homogeneous precipitation of rare-earth ions co-doped fluorite-type Pb(x)Cd1-xF2 nanocrystals of about 10 nm in diameter in the glass matrix. Under single 808 nm laser excitation, intense red, green and blue up-conversion luminescences were simultaneously observed in these transparent nano-glass-ceramics owing to the successive energy transfer from Nd3+ ions to Ho3+ and Tm3+ via Yb3+ ions. Various colors of luminescence, including bright perfect white light, can be tuned by adjusting the concentrations of the Tm3+ ions in the material. A possible energy transfer process and up-conversion luminescence mechanism in the nano-glass ceramics are proposed and discussed. PMID- 20355611 TI - Dependence of infrared-to-ultraviolet emission enhancement on Yb3+, Er3+:CaF2 nanoparticle dimension. AB - In the nanocomplexes with Yb3+, Er(3+)-codoped calcium fluoride (CaF2:Yb3+, Er3+) nanoparticles, the infrared (IR)-to-ultraviolet (UV) upconversion (UC) properties were explored under 980 nm laser diode (LD) excitation. The strong enhancement of UV emission at 407 nm was observed. An UP mechanism of the materials was discussed. PMID- 20355612 TI - Study on luminescent property of Tb(3+)-doped silicate nano-scintillating glass. AB - By optimizing a Tb(3+)-doped silicate nano-scintillating glass matrix, sensitizer and brightening agent components, the processing conditions such as the melting temperature, holding time, atmosphere, and heat treatment were improved, and the temperature of the heat treatment was changed to generate BaF2 nano-crystal in the glass. The resulting nanocrystals have a better rare earth solubility and a lower phonon energy; therefore the luminescent property of Tb(3+)-doped silicate nano-scintillating glass has been noticeably improved. PMID- 20355613 TI - Synthesis of alpha-GaO(OH) nanorods and their optical properties. AB - Here, we report the synthesis of uniform alpha-GaO(OH) nanorods on Si substrates at low temperature (200 degrees C) using solvothermal technique. alpha-GaO(OH) uniform nanorods is converted to beta-Ga2O3 after annealing at 900 degrees C under ambient atmosphere. A series of electron microscopy characterizations including scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscopy (HRTEM) are used to understand the growth mechanism of alpha-GaO(OH) nanorods formation. This nanostructure emits defect-related strong PL emissions at blue (492 nm) and green (522 nm) regions and the relative intensities of these emissions peaks can be modified by varying the reaction conditions. Similarly, we also observed room temperature cathodoluminescence (CL) and the uniform CL contrast of the nanorods in their CL image indicates a homogeneous defect distribution along the nanorods. PMID- 20355614 TI - Preparation of mesoporous silica with pelagic clay and its optical property. AB - To obtain mesoporous silica with prime properties, we used pelagic clay as the raw material with the precipitation method. According to the specific surface area (SSA) of production, we optimized the technical conditions and characterized it with Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), N2 adsorption, and scanning electron microscopy (SEM). The photoluminescence (PL) and photoluminescence excitation (PLE) of mesoporous silica were tested too. FTIR indicated that the products were pure amorphous silica. XRD showed that the silica was MCM-41. The N2 adsorption test showed that it belongs to the type of Langmuir IV, the aperture is about 2.9 nm, and the distribution is uniform. The SEM test indicated that the silica aggregation is branch-like, and the mesoporous silica is hexagonal with mesh arrangement. PL and PLE spectra proved that the intensities of the PL and PLE of mesoporous silica increase with increasing SSA. PMID- 20355615 TI - Multifunctional Fe3O4/ZnO nanocomposites with magnetic and optical properties. AB - Multifunctional Fe3O4/ZnO nanocomposites were successfully synthesized through two-step solution-based methods. Fe3O4 nanoparticles were used as seeds for the deposit and growth of ZnO nanocrystals. Transmission electron microscopy (TEM) images, X-ray diffraction (XRD) patterns, and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) were employed to observe the morphology, size, structure, and crystalline phase of the nanocomposites and confirm their chemical composition. The results of magnetization curves, resonant Raman scattering, and photoluminescence spectra revealed that the nanocomposites simultaneously possessed the super-paramagnetism of Fe3O4 and the multiphonon resonant Raman scattering and photoluminescence (PL) properties of ZnO. Compared with that of pure Fe3O4, the saturation magnetization of the Fe3O4 component within the nanocomposites was enhanced. The Raman spectroscopic fingerprint of ZnO component was preserved, and the fluorescent background was efficiently reduced. The interfacial effect was found to play an important role in modulating or improving the properties of the nanocomposites. PMID- 20355616 TI - Fabrication of titania nanotube arrays in viscous electrolytes. AB - This study probes the dependence of titania nanotube arrays nanoarchitecture on different synthesis parameters in viscous electrolytes. Titania nanotube arrays were synthesized in glycerol, ethylene glycol and carboxymethylcellulose as base materials. The effects of anodization voltage and time, as well as chemical composition and pH of the electrolyte bath were studied. Nanotube arrays with an inner diameter ranging from 16 to 91 nm, and wall thickness ranging from 7 to 29 nm were fabricated in a glycerol-water electrolyte. Water content of 5 wt% or higher was found to be essential for nanotubes fabrication in glycerol electrolyte. Diameter and length were influenced by varying water content above 5 wt%. Nanotube length was found to be time dependent at high pH values. A pH value of 6 was favorable for fabrication of highly ordered and continuous nanotube arrays with length up to 900 nm. Using modified ethylene glycol (containing 2 wt% and 0.5 wt% NH4F) instead of glycerol, resulted in nanotube length up to 430 nm after 1.5 hr anodization time. With a minor modification of electrochemical anodization cell, we successfully fabricated double-sided titania nanotube arrays layers with a total thickness of 9.5 microm for the first time. Nantube arrays were successfully fabricated in 2 wt% sodium carboxy mythylcellulose aqueous electrolyte (CMC electrolyte). These nanotube arrays had an inner diameter of 42 nm similar to those fabricated in 2 wt% urea-ethylene glycol electrolyte but their length was 450 nm. PMID- 20355617 TI - Contribution of SiC and SiO2 to photoluminescence from SiC-SiO2 nanocables grown by thermal decomposition of methanol. AB - A new simple and cheap method to grow large scale SiC-SiO2 nanocables on catalyzed Si substrate directly is presented. The method is based on the thermal decomposition of methanol. The grown nanocables consisted of crystalline 3C-SiC and amorphous SiO2. A simple etching and oxidation process was used to analyze the contribution of SiC and SiO2 components to photoluminescence. PMID- 20355618 TI - Comparison of ultraviolet upconversion luminescence between thin film and bulk of calcium fluoride co-doped with Yb3+/Tm3+ ions. AB - A calcium fluoride thin film co-doped with Yb3+/Tm3+ was deposited on Si substrates by the spin-coating method using trifluoroacetic acid as a fluorine source. The scanning electron microscopy (SEM) image of the sample showed that a thin film with some cracks was formed. After annealing, the cracks disappeared, and the film became thinner. The roughness of the thin film was about 150 nm, which was confirmed by atomic force microscopy (AFM). Moreover, the upconversion luminescence properties of the thin film after annealing were studied. Under infrared light excitation, strong ultraviolet (UV) upconversion luminescence of the thin film was observed. To compare the upconversion properties, Yb3+/Tm3+ co doped calcium fluoride bulk material that has the same components with the thin film was also synthesized. Compared with the bulk material, the UV upconversion emission of thin film was more intense. The mechanism of UV upconversion was determined by analyzing the upconversion spectra. The decrease in the size of the CaF2 Yb3+/Tm3+ particles to the nano-scale in the thin film contributed to the enhancement of the UV UC luminescence. PMID- 20355619 TI - Preparation and far infrared emission properties of natural sepiolite nanofibers. AB - Sepiolite nanofibers were prepared by high-speed air current superfine technique, using natural sepiolite samples as raw materials. Through characterization by scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic contact angle meter and tensiometer (DCAMT) and Fourier transform infrared spectroscope (FTIR), it was found that the defibered sepiolite nanofibers with an average diameter of about 100 nm and length greater than 9 microm had a better far infrared emitting performance than acid-purified sepiolite as the contrast sample, and the defibering treatment led to the improvement of far infrared emitting performance of sepiolite due to the increase of surface free energy, the increase of infrared active bond vibrations, and the decrease of cell volume caused by the distortion of structural channel. PMID- 20355620 TI - A large quantity synthesis of ZnO nanoneedles and their polarity determination. AB - A large quantity of uniform ZnO nanoneedles has been synthesized by thermal evaporation method. Both single and double tip ZnO nanoneedles were found coexistence in the as-synthesized products. The single tip nanoneedles are major products in the synthesis and a few double tip nanoneedles were also observed. The polarity of the nanoneedles was characterized by convergent beam electron diffraction (CBED) and the simulation results reveal that the polarity of the ZnO (0001) surface directs the preferential growth of the nanoneedles. It is also found that most of the double tip nanoneedles are originated from the joint growth of two single tip nanoneedles with a kink in the middle and smooth ones might be generated from forming thin layer of cubic structures in the double nanoneedle tips. A large quantity of ZnO nanorod building blocks without tips was also achieved by fast cooling. The formation of the nanoneedles and nanorods can be attributed to different cooling speeds in our experiments. The sharp single nanoneedle tip can be potentially used as scanning probe microscope or field emission tips. PMID- 20355621 TI - Synthesis and upconversion luminescence of NaYF4:Yb3+,Tm3+/TiO2 nanocrystal colloidal solution. AB - NaYF4:Yb3+,Tm3+ upconversion nanocrystals were synthesized with oleic acid as a capping ligand. The as-prepared samples were redispersed in cyclohexane, forming transparent and stable solutions which perform bright blue upconversion. Inducing TiO2 as the outer layer of the fluoride cores, we investigated the effect of TiO2 on the upconversion process. The transmission electron microscopy (TEM) analysis indicated that titania successfully formed a coating layer on the surface of NaYF4:Yb3+, Tm3+ nanoparticles, and the average diameters of the NaYF4:Yb3+,Tm3+ nanocrystals and the NaYF4:Yb3+, Tm3+/TiO2 nanoparticles are about 14 and 40 nm, respectively. Under the excitation of a 980 nm laser, NaYF4:Yb3+, Tm3+ nanocrystals and TiO2-coated NaYF4:Yb3+, Tm3 core/shell structure sample exhibited distinct upconversion luminescent properties. PMID- 20355622 TI - Synthesis and upconversion luminescence of YF3:Yb3+ Tm3+ and TiO2-coated YF3:Yb3+, Tm3+ microcrystals. AB - YF3:Yb3+, Tm3+ microcrystals were prepared by a microemulsion method. The microcrystals were coated with TiO2 by hydrolysis of titanium n-butoxide (TBOT). Transform electron microscopy and X-ray diffraction were used to characterize the core/shell materials. The results indicated that the low TBOT/YF3 molar ratio was favorable to preparing the uniform TiO2 coatings. The upconversion luminescence properties of YF3:Yb3+, Tm3+ and TiO2-coated YF3:Yb3+, Tm3+ microcrystals were studied under 980-nm excitation. The 1I6 --> 3H6, 1I6 --> 3F4, 1D2 --> 3H6, 1D2 - > 3F4, 1G4 --> 3H6, and 1G4 --> 3F4 emissions were observed. The upconversion mechanisms were discussed in detail. PMID- 20355623 TI - Synthesis of well dispersed uniform sub-4 nm Y2O3:Eu3+ colloidal nanocrystals. AB - Well dispersed uniform sub-4 nm Y2O3:Eu colloidal nanocrystals have been synthesized through the non-hydrolytic high-temperature thermal decomposition technique. The as-synthesized nanocrystals can be stably dispersed in nonpolar solvents due to the capping organic ligands on their surface. Compared with bulk materials, the nanocrystals exhibited different luminescence features, including the intensity enhancement of the 5D0 --> 7F4 transition observed in the emission spectrum. PMID- 20355624 TI - In-dopants effect on the photoluminescence properties of YVO4 nanophosphors. AB - The powders of Yttrium vanadate (YVO4) with In-dopants were synthesized by solid state reactions, and X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) absorption spectra, photoluminescence (PL) spectra, and the luminescence intensity change were used to characterize the samples. The results of XRD indicated that the YVO4:In3+ samples remained in pure cubic phase. TEM illustrated that the powders mainly consisted of grains with an average size of 100 nm. Under the excitation of 320 nm, the YVO4:In3+ single crystalline samples exhibited emission ranging from 350 to 700 nm. The emission intensity of YVO4:In3+ increased with increasing indium concentration in the lower indium concentration region until the saturated PL intensity was reached, and the strongest white fluorescence was observed when the In3+ doping concentration was 2% at 900 degrees C. The luminescent intensity of YVO4:In3+ (2%) was 9.6 times as strong as that of non-doped YVO4. The nanophosphors emit white luminescence owing to broad charge transfer in crystal lattice is due to the addition of In3+ to capture the UV radiation. PMID- 20355625 TI - Device architecture and precision nanofabrication of microring-resonator filter banks for integrated photonic systems. AB - To achieve the maximum benefit of electronic-photonic integrated circuits wavelength-division multiplexing must be used. This requires the design and fabrication of a highly integratable photonic device, capable of performing multiplexing/demultiplexing operations with low loss and minimal crosstalk. A filter bank consisting of high-index-contrast microring-resonator filters, with accurately spaced resonant frequencies can meet these requirements. This paper describes the basic architecture of microring-resonator filter banks, and how to maximize performance while keeping fabrication challenges reasonable. The greatest challenge in fabricating such devices is achieving the dimensional precision, on the scale of tens of picometers, needed to attain accurately spaced resonant frequencies. To do this, a fabrication method based on varying the electron-beam dose during scanning-electron beam lithography is used. This approach is used to create a dual twenty-channel filter bank, comprised of second order silicon-rich silicon nitride microring resonators. The average resonant frequency spacing is off from the target spacing by only 3 GHz, corresponding to a dimensional precision of 75 pm. This approach is also shown to be compatible with the fabrication process for silicon microring resonators. Furthermore, it is shown that any remaining resonant frequency errors can be corrected with postfabrication thermal tuning. Also, a method of using the contra-propagating mode of a microring-resonator filter is demonstrated, enabling a single filter bank to multiplex/demultiplex two signals at the same time. PMID- 20355626 TI - Electrochemical and photoelectrochemical investigation of new electrostatic self assembled films based on Prussian blue and a binuclear Ru(II) complex. AB - New hybrid multilayer films containing Prussian blue (PB) and a binuclear Ru(II) complex were successfully fabricated using the electrostatic layer-by-layer self assembly technique. The process was carefully monitored by ultraviolet-visible (UV-vis) spectroscopy. A linear increase in the UV-vis absorbance with the number of deposited layers indicated that the film deposition was uniform and reproducible. The electrochemical and photoelectrochemical properties of these hybrid multilayer films were investigated in an aqueous Na2SO4 solution. PB and the binuclear Ru(II) complex assembled in the film were redox active with surface confined characteristics. The surface concentration and molecular area of RuL in the film were calculated according to a UV-vis absorption spectrum and cyclic voltammetry, respectively. The photocurrent generated by switching on the light irradiation of the film increased linearly as the deposited bilayers increased. The photocurrent action spectrum was in agreement with metal-to-ligand charge transfer (MLCT) band of RuL in the absorption spectrum, which indicated that the photocurrent was generated based on MLCT excitation of the RuL in the (PB/RuL) film. PMID- 20355627 TI - Instense red phosphors for UV light emitting diode devices. AB - Ca(x)Sr1-x-1.5y-0.5zMoO4:yEu3+ zNa+ red phosphors were prepared by solid-state reaction using Na+ as charge supply for LEDs (light emitting diodes). The content of charge compensator, Ca2+ concentration, synthesis temperature, reaction time, and Eu3+ concentration were the keys to improving the properties of luminescence and crystal structure of red phosphors. The photoluminescence spectra shows the red phosphors are effectively excited at 616 nm by 311 nm, 395 nm, and 465 nm light. The wavelengths of 395 and 465 nm nicely match the widely applied emission wavelengths of ultraviolet or blue LED chips. Its chromaticity coordinates (CIE) are calculated to be x = 0.65, y = 0.32. Bright red light can be observed by the naked eye from the LED-based Ca0.60Sr0.25MoO4:0.08Eu3+ 0.06Na+. PMID- 20355628 TI - Synthesis of ZnO nanosheets by microwave thermal vapor method. AB - Two-dimensional single-crystalline ZnO nanosheets have been successfully synthesized in high yield from a mixture of ZnO and graphite powders via a microwave thermal vapor process. Morphological analysis indicates that the widths and thickness of the nanosheets are in the range of several to tens of microm and 20-80 nm, respectively. ZnO nanosheets grew along the [0001] and [2110] directions, and the width-to-thickness ratio of the nanosheets could reach up to 1,000. The room temperature photoluminescence revealed that the ZnO nanosheets exhibited a weak ultraviolet (UV) emission at approximately 378 nm and a strong green emission at approximately 505 nm. PMID- 20355629 TI - Electrospinning preparation of uniaxially aligned ternary terbium complex/polymer composite fibers and considerably improved photostability. AB - In order to improve photoluminescence properties, terbium complex Tb(acac)3phen (acacacetylacetone, phen-1,10-phenanthroline) was incorporated into polystyrene (PS), polyvinylpyrrolidone (PVP), and polymethylmethacrylate (PMMA) matrixes and electrospun into various aligned composite fibers. Their morphology, structure and photoluminescence properties were systematically characterized and studied. The results demonstrated that under the ultraviolet (UV) light exposure, the emission intensity for 5D4 --> 7F(J) of Tb3+ in the composite fibers considerably increased, while it was greatly quenched in the pure complex, implying remarkably improved photostability in the composites. The composite fibers also demonstrated much better temperature stability of photoluminescence over the pure complex. PMID- 20355630 TI - Microstructure and far infrared emission properties of tourmaline powders eroded by hydrochloric acid. AB - The microstructure and far infrared emission properties of tourmaline powders eroded by hydrochloric acid were investigated. The indexes including crystal structure, unit cell volume, microstructure and infrared spectra were characterized by X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. The results show that the crystal structure was not changed; however, the unit cell volume decreased, the angularities of tourmaline particles became smooth, and there appeared nanohollows on their surfaces. The infrared emission properties were enhanced at proper concentrations of hydrochloric acid solutions. PMID- 20355631 TI - Effects of particle size on far infrared emission properties of tourmaline superfine powders. AB - Tourmaline superfine powders with different particle sizes were prepared by grinding, superfine ball milling, and high-speed centrifugation. The powders were characterized by scanning electron microscopy, X-ray diffraction, dynamic contact angle meter and tensiometry, and Fourier transform infrared spectrometry. The results show that tourmaline powders exhibit improved far infrared emission properties as the particle size decreases. The increased surface free energy and proportion of the polar component are considered to play an important role for their properties. The spontaneous polarization is increased, and the dipole moment of tourmaline is stimulated to a high energy level more easily for the chemical bond vibration, so that the energy is apt to emit by transition. In the range of 2000-500 cm(-1), the emissivity values of the samples with D50 size of 2.67 microm and 0.2 microm are 0.973 and 0.991, respectively. PMID- 20355632 TI - TEM observation and study of three-layer Al2O3/ZrO2 ceramics. AB - The micrograph and the crystal orientation relationship of Al2O3/ZrO2 laminated ceramics were studied with the help of transmission electronic microscope (TEM). The experiment results showed that: the Al2O3 and ZrO2 grain sizes were small and the links among the crystals were good. No flaws such as pores or micro-cracks were observed in the micro-structure. Further TEM analyses and electronic diffraction spot calculation proved that interface compressive stress could greatly restrain the transformation of the tetragonal phase and increase the contents of transformable tetragon, but did not change the orientation relation between the tetragonal and monoclinic phase, while (100),m//(010), still exist in the three-layer ZrO2 ceramics. PMID- 20355633 TI - Size- and shape-controlled synthesis of monodisperse vanadium dioxide nanocrystals. AB - Highly monodisperse VO2 nanocrystals with finely defined sizes and shapes were synthesized for the first time by thermolysis of single source vanadium precursor in high boiling point solvents of oleic acid (OA), oleylamine (OM), and octadence (ODE). The resulting VO2 nanocrystals were characterized by means of powder X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X Ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). It was revealed that the low valence vanadium oxide of VO2 nanocrystals was successfully synthesized via this approach, and the obtained VO2 nanocrystals displayed uniform sizes and narrow size distribution with size variation in range of approximately 4-20 nm under various synthetic conditions. The previously unknown cubic, polyhedral shaped VO2 nanocrystals were achieved as well through modulating the preparative conditions. The solvent composition and precursor concentration are found to have profound effects on the sizes and shapes of the final VO2 nanocrystals. It is expected that the obtained VO2 nanocrystals with finely controlled sizes and shapes may be valuable candidates for studying and realizing the new size- and shape- dependent optical and electrical properties of VO2 materials in the nanoscale realm, and the novel synthetic method is potentially useful for the controlled synthesis of high quality doped VO2 and other vanadium oxides nanocrystals. PMID- 20355634 TI - Enhanced fluorescence from CdTe quantum dots self-assembled on the surface of silver nanoparticles. AB - This paper presents an investigation on the fluorescent properties of semiconductor CdTe quantum dots (QDs) self-assembled on the surface of PVP (polyvinylpyrrolidone)-capped silver nanoparticles (NPs) by the ligand field effect. A significant 2.5-fold enhancement in the integrated fluorescence intensities, red shift of fluorescence peak, and obvious decrease of lifetime were observed in the CdTe QDs assembled on the Ag NPs in comparison with the pure CdTe QDs. The fluorescence enhancement factor and red shift were found to depend on the Ag NP concentration. The fluorescence enhancement was attributed to a highly localized electromagnetic field on the Ag NPs generated by the surface plasma and the change in the surface trap state of the CdTe QDs originating from plasma oscillations in the Ag NPs. It is first proposed that the surface passivation of CdTe QDs is also an important factor for metal-enhanced fluorescence. The surface defects of CdTe QDs can be modified by the Cd-O coordination interaction between the CdTe QDs and PVP molecules, which will cause the trap state density and luminescence lifetime to decrease. The surface passivation of CdTe QDs can also improve fluorescence quantum yield and lead to the red shift of the fluorescence peak. Compared with previous reports, the occurrence of the self-assembly of CdTe QDs on the surface of PVP-capped Ag NPs is fairly simple and easy. From a practical point of view, the combination of CdTe QDs with Ag NPs may lead to the fluorescence enhancement, which could be utilized in a variety of chemical and biological detection applications. PMID- 20355635 TI - Aloetic-shaped SiC nanowires: synthesis and field electron emission properties. AB - Novel ordered aloetic-shaped SiC nanowires were synthesized on a Si (100) substrate by reacting methane with silicon dioxide using iron as a catalyst. Their structure and chemical composition were studied by scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The wires have a tapered aloetic structure with a top diameter about 50-80 nm and a length about 10 microm. The field emission properties of the aloetic nanowires were investigated. A stable emission with current density of 0.525 mA/cm2 at an applied electric field of 2.2 V/microm and a low turn-on electric fields of 1.4 V/microm were observed. The excellent field emission properties indicate that the aloetic-shaped SiC nanowires may have potential applications in flat panel displays and electron field-emitting devices. PMID- 20355636 TI - Self-assembled films of a biferrocenyl-containing hemicyanine derivative with SiW12O40(4-): preparation, UV-visible spectroscopy and electrochemical properties. AB - Electrostatic self-assembled films were successfully prepared by alternating deposition of SiW12O40(4-) and a biferrocenyl-containing hemicyanine derivative on quartz or indium-tin-oxide coated glass substrates. The films were characterized by UV-visible absorption spectroscopy and cyclic voltammetry. PMID- 20355637 TI - Ultraviolet-blue photoluminescence of ZnSe quantum dots. AB - Zinc blende, sphericity, monodisperse, high luminescence ZnSe quantum dots (QDs) were synthesized by a one-step mild hydrothermal route with Zn and Se dissolved in aqueous NaOH as the source material. The structure and the morphology of the sample were examined by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results indicated that the products were cubic blende ZnSe ranging from 3.2 to 4.5 nm in size. TEM images showed that the QDs have very good dispersibility and distribution. The characteristic features of the absorption and photoluminescence spectra of ZnSe quantum dots were studied at room temperature. Compared with the bulk ZnSe, the absorption edges and luminescent peaks of ZnSe QDs were blue shifted to higher energies due to the quantum confinement effect. Photoluminescence at ultraviolet excitation showed the strong emission at 390 nm related to the higher excitonic states. ZnSe QDs exhibiting photoluminescence line widths as narrow as 40-60 nm. Meanwhile, we simply explored the theoretical mechanism of luminescence in ZnSe QDs and analogized the relation of various point defect concentrations of ZnSe. PMID- 20355638 TI - Characterization and water activation behavior of tourmaline nanoparticles. AB - Tourmaline nanoparticles were prepared by using a wet mechanochemisty method. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) results showed that the tourmaline grain size is in the range from tens of nanometers to several hundred nanometers. Through characterization by Fourier transform infrared spectroscope, it was found that the milled tourmaline had a better far infrared emitting performance due to the increase of radiation surface area. The structure change of liquid water clusters induced by the addition of tourmaline nanoparticles was observed by nuclear magnetic resonance (NMR). The results showed that the addition of tourmaline nanoparticles reduced the 17O NMR full width at half maximum intensity (FWHM) for treated water and the volume of water molecule clusters. The feature of activated water was enhanced with decreasing tourmaline nanoparticles size due to the cooperation of strong surface electric field and high far infrared emissivity. Moreover the activation time can be maintained at 480 h suggesting the potential application of tourmaline in wastewater treatment. PMID- 20355639 TI - Characterization and optical transition in tb-doped 12CaO x 7Al2O3 powders. AB - Tb-doped 12CaO x 7Al2O3 (C12A7:Tb3+) powders with strong green emission were prepared using the sol-gel method. X-ray diffraction, micro-Raman spectra, scanning electron microscopy and absorption spectra showed that C12A7:Tb3+ powders with grain size of 200-300 nm were synthesized. Porous powders could be formed as the concentration of Tb3+ was 5 at%. The absorption band around 209 nm was attributed to the host lattice absorption, and the bands around 255 nm and 274 nm were related to the 4f-5d transitions of Tb3+. The absorption intensity of the visible region was enhanced due to the presence of one 100 nm-diameter hole in every grain of C12A7:Tb3+ powders. The emission spectra showed noticeable influence of Tb-Tb cross relaxation, which favored the green photoluminescence (PL) over the blue PL. The study on the concentration quenching indicated that the energy transfers depopulating the 5D3 and 5D4 levels were assigned to the mechanisms of electric dipole-dipole and exchange interaction, respectively. PMID- 20355640 TI - Study on luminescence properties of Eu2+ in BaAl12O19 matrix. AB - Eu(2+)-doped BaAl12O19 phosphors were prepared using the sol-gel method, and their structure and luminescence properties were characterized by X-ray diffraction (XRD) analysis and fluorescence spectrometry. The results showed that a single hexagonal BaAl12O19 crystal structure was synthesized and the emission spectrum of BaAl12O19:Eu exhibited a broad asymmetric band from 375 to 600 nm, which was composed of three emission peaks at 438, 462, and 511 nm. The effects of crystallization temperature, Eu2+ concentration, and Al3+ content on the occupation of Eu2+ in three crystallographic positions were investigated. The emission intensity of 438 nm increased with increasing crystallization temperature, while the emission intensity of 462 and 511 nm increased with the increase of Eu2+ concentration and Al3+ content. PMID- 20355641 TI - Synthesis of bamboo-like 3C-SiC nanowires by microwave assisted carbothermal reduction. AB - In this paper, bamboo-like 3C-SiC nanowires were synthesized in minutes without a metal catalyst by a simple, fast, and low-cost microwave method. The as synthesized nanowires were studied by X-ray diffraction, scanning electron microscopy, Raman spectra, and transmission electron microscopy. The results showed that the bamboo-like nanowires have a stem of cubic 3C-SiC and nodes consisting of a high number of stacking faults, which are crystalline 3C-SiC with a diameter of 20-100 nm and a length around several microns. A possible mechanism for growing bamboo-like SiC nanowires in a microwave is also proposed. PMID- 20355642 TI - Synthesis and enhanced photoluminescence of surface-modified barium borate nanorods. AB - Well-dispersed barium borate nanorods with uniform diameters were synthesized successfully, using Na2B4O7 x 10H2O and Ba(NO3)2 as raw materials and oleic acid as a modifying agent. Oleic acid was used to modify the surface property of nanorods prepared from the precipitation reaction. TEM images confirmed that the synthesized sample presented nanorod morphology with a length of about 200-400 nm and an average diameter of 20 nm. Moreover, the photoluminescence properties of both pure and modified BaB2O4 nanorods were tested. After the surfaces of the nanorods were modified with oleic acid, the visible light emission of the sample centered at 380 and 400 nm became more intensive. It was discussed that the enhancement of the luminescence intensity was attributed to the formation of surface BaB2O4/oleic acid complexes. PMID- 20355643 TI - Upconversion emission of BaTiO3:Er3+ nanocrystals: influence of temperature and surrounding medium. AB - Here, we report the role of crystallite size and surrounding medium on the upconversion emission of Er3+ in BaTiO3 oxide nanocrystals. The samples were prepared by sol-emulsion-gel method and heat-treated at two different temperatures yielding powders containing nanoparticles of different sizes. Green (550 nm) and red (660 nm) upconversion emission were observed at room temperature from the 4S3/2 and 4F9/2 levels of BaTiO3:Er3+ nanocrystals. The pump power dependence study confirms that all these upconversion emission lines are a two photon absorption process. We observed that the luminescence lifetime is shorter for the sample containing smaller particles. Optical thermometry experiments were performed in air, water and glycerol in a temperature range from 27.1 up to 47.1 degrees C aiming to use this material as a biological temperature sensor. PMID- 20355644 TI - Combustion synthesis of Eu(3+)-activated Y2Hf7O17 powders. AB - Eu3+ doped-Y2Hf7O17 nanopowders were synthesized by the chemical self-combustion method at low temperature. X-ray diffraction, transmission electron microscopy, and scanning electron microscopy were employed to analyze the phase composition and the characteristics of the nanopowders. The excitation and emission spectra were analyzed with a fluorescence photometer. Results show that nanoscale powders calcined at 800 degrees C have good luminescent properties. There are two peaks in the emission spectra. One is at 595 nm, and the other is at 614 nm. Analysis of X-ray diffraction and photoluminescence spectra reveals that Y2Hf7O17 is cubic phase. The sample doped with 14 mol% Eu3+ has the maximum luminescent intensity. PMID- 20355645 TI - The luminescence of nanoscale Y2Si2O7:Eu3+ materials. AB - The Y2Si2O7:Eu3+ sample was prepared with the sol-gel method. The Y2O3:EU3 was dispersed in SiO2, and the complex Y2Si2O7:Eu3+ particles were synthesized at high annealing temperature. The sample consisted of nearly spherical particles with an average size about 60 nm. The ultraviolet excitation spectra and emission spectra were measured. The sample excited by short ultraviolet light showed strongly red luminescence and fine monochromaticity. The luminescence was strongest from the 5D0 --> 7F2 electric dipole transition located at 611 nm. The excitation spectra of Y2Si2O7:Eu3+ excited with ultraviolet lights showed that the peak of the Eu(3+)-O2- charge transition band located at about 240 nm. During monitoring of different emission peaks of 5D0 --> 7F2, the charge transition band in the excitation spectra shifted, and the relative intensity of emission spectra changed obviously under the excitation of different ultraviolet wavelengths. These results confirmed that the Eu3+ could be excited with ultraviolet radiation of different wavelengths. At low temperature, using Eu3+ ions as fluorescence probes, we monitored the emission peaks of 5D0 --> 7F1 and 5D0 --> 7F2 transitions and measured the excitation spectra of 7F0 --> 5D0, 5D0 --> 7F1, and 5D0 --> 7F2 site-selective excitation spectra. These results indicated that Eu3+ ions are located in different local environments in the Y2Si2O7 host. PMID- 20355646 TI - Effects of SO4(2-) or SiO3(2-) doping on the photoluminescence of NaEu(MoO4)2 nanophosphors for light-emitting diodes. AB - A series of red nanophosphors including NaEu(MoO4)2-x(SO4)x as well as NaEu(MoO4)2-x(SiO3)x (x = 0, 0.10, 0.20, 0.30, 0.40) were synthesized by hydrothermal and subsequent heat-treatment processes. The as-prepared pure and anion (SO4(2-) or SiO3(2-))-doped NaEu(MoO4)2 phosphors were indexed as a scheelite structure, which was revealed by X-ray diffraction data. The morphologies of SO4(2-)-doped NaEu(MoO4)2 powders were almost regularly spherical, and their grain sizes ranged from 300 to 400 nm. However, the grains of SiO3(2-)-doped phosphors appeared to be seriously inordinate and unconsolidated, as indicated by their scanning electron microscopy studies. All of the samples were excited with near-UV 395 nm light and showed the characteristic red emission of the Eu3+ 5D0 --> 7F2 transition. With the incorporation of SO4(2-) into the host, the red emission intensities of Eu3+ increased obviously and reached a maximum at x = 0.30. Nevertheless, the intensities of Eu3+ emission reduced dramatically after the SiO3(2-) doping. The optimized NaEu(MoO4)1.70(SO4)0.30 nanophosphor powders, with well-distributed fine grains and strong emission intensity, may be applied in the fabrication of phosphor-converted light-emitting diodes (LEDs). PMID- 20355647 TI - Photoinduced organic field-effect transistor based on poly-3-hexyl-thiophene active layer. AB - Top-contact organic field-effect transistors (OFETs) were fabricated by using a poly-3-hexyl-thiophene (P3HT) active layer. The characteristics of OFETs without and with the light-illumination were investigated. The experimental results indicate that the light has a great influence on the OFETs properties. After the light-illumination, the drain current and carrier mobility were increased, the threshold was decreased, and the on/off ratio was enhanced. PMID- 20355648 TI - Energy and charge transfer dynamics between Alq3 and CdSeS nanocrystals. AB - The photoluminescence properties of the blend films consisting of organic small molecules and nanocrystals (NCs)--Alq3 and CdSeS NCs--were studied by steady state and time-resolved photoluminescence (PL) spectroscopy with different excited wavelengths. Both the fluorescence intensity and lifetime are intensively dependent on the NC concentration. The detailed analysis of experiment data proves that Forster energy transfer from the Alq3 to the NCs exists simultaneously with the charge transfer and both compete with each other in the blend films. PMID- 20355649 TI - Optical properties of LaF3:Er,Yb nanoparticle-doped organic-inorganic hybrid material. AB - Oleic acid (OA)-modified LaF3:Er,Yb nanoparticle-doped organic-inorganic hybrid material (OIHM) was prepared. The absorption spectrum and photoluminescence spectrum were analyzed. The full width at half maximum (FWHM) of the photoluminescence spectrum was about 83 nm. The Judd-Ofelt theory was used to analyze the absorption spectrum of Er3+ and obtain the intensity parameters: omega2 = 2.11 x 10(-20) cm2, omega4 = 0.78 x 10(-200 cm2, omega6 = 0.56 x 10( 20)cm2. The line strengths predict spontaneous transition probabilities, and the radiative lifetimes are calculated with the Judd-Ofelt intensity parameters. The calculated radiative lifetime of the excited 4I13/2 state of Er3+ is 13.34 ms. Based on the parameters we calculated, OA-modified LaF3:Er,Yb nanoparticle-doped OIHM is a potential material for polymeric optical waveguide amplifiers. PMID- 20355650 TI - Photoluminescent properties of nanoscaled Zn2SiO4:Mn2+ green phosphor under vacuum ultraviolet excitation. AB - Nanoscaled Zn2SiO4:Mn2+ green phosphor was synthesized through the hydrothermal method using Zn(CH3COO)2, Mn(CH3COO)2, and (C2H5O)4Si as starting materials. According to the XRD results, the pure hexagonal structured zinc silicate nanophosphor could be synthesized at a low temperature of 140 degrees C. The TEM image showed that the obtained nanophosphor was composed of rod-like particles with average diameter of 100 nm and length of 150 nm. When the cetyltrimethyl ammonium bromide as the surfactant molecules was adopted into the hydrothermal procedure, the morphology and the particle size of the phosphor could be controlled. The uniform spherical nanoparticles with the diameter of 60 nm were synthesized. Under vacuum ultraviolet excitation, the nanoscaled Zn2SiO4:Mn2+ phosphor exhibited the strongest broad emission at about 523 nm which attributed to the 4T1 --> 6A1 transition of Mn2+. The photoluminescence intensity of the phosphors increased along with the increasing hydrothermal temperature due to higher crystallinity. It was found that the Zn2SiO4:Mn2+ nanospheres had higher photoluminescence intensity than the rod-like particles due to fewer defects, which provide non-radiative recombination routes in the Zn2SiO4:Mn2+ nanosphere phosphors. PMID- 20355651 TI - The synthesis of BaMgAl10O17:Eu2+ nanorods and their luminescence properties under UV and VUV excitation. AB - BaMgAl10O17:Eu2+ nanorods were synthesized by the sol-gel process at 1,250 degrees C, while bulk phosphor was prepared by conventional solid-state reaction at 1,600 degrees C. The naonrods had a homogeneous grain size 80-100 nm in diameter and 0.8-1 microm in length. Under 254 nm excitation, the emission intensity of these nanorods was 90.12% of the commercial phosphor. Under 147 nm excitation, the intensity rate was 78.15%. The color coordinates were (0.145, 0.062) under ultraviolet (UV) excitation and (0.143, 0.068) under VUV excitation. Compared with the standard blue fluorescence (0.14, 0.08), the y value was obviously decreasing. These low y values suggested that these BAM nanorods were good for restricting the decrease of BAM effciency during heating. PMID- 20355652 TI - Synthesis and characterization of gold nanoparticles based on low generational triethylene glycol-polyamidoamine dendrimers. AB - Low generational polyamidoamine (PAMAM) dendrimers with triethylene glycol (TEG) core and ester groups at the surface have been synthesized and investigated as templates for preparation of gold nanoparticles (AuNPs), by reducing chloroauric acid (HAuCl4) with potassium borohydride (KBH4) in N,N-dimethylformamide (DMF). UV-vis absorption spectroscopy, fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were used to confirm the formation of AuNPs. Stable gold nanoparticles with particle size around 10 nm were obtained and the interaction between the dendrimers and Au moieties is discussed. PMID- 20355653 TI - Probing the visible luminescence mechanism in ZnO nanoparticles by band edge modulation. AB - The visible luminescence mechanism of ZnO is an important but controversial problem. In this paper, we report the structural and optical properties of Mg doped ZnO nanoparticles (approximately 3-4 nm) synthesized via the sol-gel method. X-ray diffraction (XRD) analysis and absorption spectra observations revealed that Mg ions replace Zn ions in the lattice. In the room temperature photoluminescence (PL) spectra, three emission bands, ultraviolet (UV), blue, and green, were observed. With increasing concentration of Mg, the near band edge (NBE) emission band progressively shifted to the higher energy side. The green emission in the visible emission band, however, presented an inconspicuous shift. The reason is probably that the bottom of the conduction band in ZnO is determined by the Zn 4s state, and the top of the valence band is determined by the O 2p state. Mg ions in ZnO substitute for zinc ions and enter a slightly distorted tetrahedral site, which causes the bottom of the ZnO conduction band to be shifted to higher energy and leaves the top of the valence band unchanged. This combined with the fact that the deep level position is insensitive to the shift of the band edge led us to conclude that the green emission originates from electronic transition between the deep defect level and the top of the valence band (or very shallow acceptor level). PMID- 20355654 TI - Synthesis and optical properties of BaFBr and BaFBr:Eu2+ nanoparticles. AB - BaFBr nanoparticles were synthesized by cetyltrimethylammonium bromide (CTAB)/2 octanol/water microemusion systems. X-ray diffraction (XRD) analysis shows that depending on the molar starting ratio of NH4F to NH4Br, stoichiometric BaFBr with or without a BaF2 phase is obtained. As the ratio of NH4F to NH4Br reduced from 1.0:1.0 to 1.0:4.0, the product formed pure BaFBr. Calculations using the Debye Scherrer equation from line widths of the XRD and transmission electron microscopy (TEM) images show particle sizes of less than 100 nm. Europium-doped BaFBr nanoparticles (with molar ratio of Ba:Eu equal to 1:0.005) were also synthesized according to the conditions of the pure BaFBr product. Photoluminescence (PL) and photostimulated luminescence (PSL) signals of europium doped BaFBr, however, were not measurable. Thermal processing for 20 min at 800 degrees C in a reducing atmosphere leads to the observation of Eu2+ fluorescence and PSL. PMID- 20355655 TI - Formation and luminescence of sodium rare earth fluoride nanocrystals in the presence of chelators. AB - The single crystal structure of sodium yttrium fluoride (NaYF4) nanoparticles formed mainly by aggregation in aqueous phase was first confirmed by high resolution transmission electron microscope (HRTEM). Then, effects of reactant concentrations and pH on the formation of NaYF4 nanocrystals were investigated and described in the presence of sodium citrate (Na-citrate). The results showed that the non-aggregation formation of NaYF4 was dominant under a low concentration range of reactants, and the aggregation formation was dominant under a high concentration range of reactants. For comparison, NaYF4 nanocrystals were also synthesized by co-precipitation in the presence of various other chelators, not only amino-carboxyl (H2N-C) types involving (Na-EDTA) and sodium nitrilotriacetate (Na-NTA) but also hydroxyl-carboxyl (HO-C) types including sodium citrate (Na-citrate), sodium malate (Na-malate), and potassium sodium tartrate (K, Na-tartate). All the chelators showed a similar influence on the particle formation. However, the size of the final product was different corresponding to the different chelators. An upconversion fluorescent material, cubic NaYF4 nanocrystal co-doped with ytterbium and erbium with diameter about 10 nm was successfully achieved at room temperature. Under 980 nm laser excitation, the red emissions at 652 and 679 nm were much stronger than green emissions at 520 and 541 nm. Additionally, effects of concentrations of the different chelators on the fluorescent properties of the formed NaYF4:Yb, Er nanocrystals were also investigated. Different chelators affected the fluorescent properties differently, according to their respective physical and chemical properties. PMID- 20355656 TI - Preparation, characterization, and photoelectric properties of an electrostatically self-assembled film based on colloidal tungsten trioxide and a dinuclear Ru(II) complex. AB - An electrostatic self-assembled film based on a tungstic acid colloidal solution and a dinuclear Ru(II) complex [(bpy)2Ru(bpbh)Ru(bpy)2](CIO4)4 [where bpy = 2,2' bipyrizine and bpbh = 1,6-bis-(2-(2-pyridyl)benzimidazoyl)hexane] has been prepared and characterized by means of ultraviolet-visible absorption and emission spectroscopy and cyclic voltammetry. The photoelectrochemical properties of the films have also been studied. A large anodic photocurrent of 0.8 microA/cm2 was observed when a monolayer film of ITO/WO3/the Ru complex was irradiated with polychromatic light (730 nm > lambda > 325 nm) at a positive applied potential of 0.6 V versus a saturated calomel electrode, four-fold that observed under the same experimental condition for the ITO electrode covered with only a monolayer of WO3 without the Ru(II) complex, indicating that the the anodic photocurrent mainly arose from the electron injection from the photoexcited Ru(II) complex to the conduction band of WO3. PMID- 20355657 TI - CdO/ZnO core/shell nanostructures grown from single molecular precursors. AB - Quadrilateral CdO nanoparticles were grown from cadmium cupferronate complex by injecting the precursor dissolved in octylamine into trioctylamine at 220 and 250 degrees C. CdO/ZnO core/shell structures were synthesized with a method similar to that of growing CdO cores by injecting the shell precursor following the growth of cores. The shell growth temperature was adjusted from 160 to 130 degrees C, and the shell precursor supply speed was adjusted from 4 to 8 ml/h. The obtained nanostructures were characterized by X-ray diffraction, high resolution transmission electron microscope, and ultraviolet-visible spectrophotometer. No core/shell structures formed if the shell precursor injection speed was as high as 8 ml/h. A very thin layer of ZnO shells would form on CdO cores if the shell precursor was injected at a speed of 4 ml/h at temperature of 160 degrees C, and the shells had good crystal quality. CdO/ZnO core/shell nanostructures were inclined to be spherical, and no homogeneous formation of ZnO nanoparticles was observed if the shell precursor injection temperature was lowered to 130 degrees C. PMID- 20355658 TI - Fabrication of nano-hydroxyapatite using a novel ultrasonic atomization precipitation method. AB - A novel technique to synthesize hydroxyapatite (HAP) with nanocrystalline structure was developed in this study. Nanocrystalline HAP was prepared by a precipitation method with aid of ultrasonic atomization using Ca(NO3)2 x 4H2O and (NH4)2HPO4 as raw materials. The crystallization and the morphology of the prepared nanopowder were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The obtained powder was 30-40 nm in size and homogenous. The effect of some surfactants on the crystallization and morphology of HAP nanoparticles was also investigated. The results showed that the synthesis method used in this study can effectively shorten the reaction time while improving the homogeneity of the powder when compared to other published methods. It was also found that the addition of a small amount of surfactant glycine during the precipitation synthesis can reduce the agglomeration of the HAP nanoparticles. PMID- 20355659 TI - Synthesis and luminescent properties of nanoscale Gd2Si2O7:Eu3+ phosphors. AB - Gd2Si2O7:Eu3+ nanoparticles were prepared by the sol-gel method with citric acid as an additive in the precursor solutions. The crystal structure was analyzed by means of X-ray diffraction (XRD). The results indicate that the alpha-Gd2Si2O7 powders in size 35 nm are obtained at a synthesis temperature of 1,100 degrees C, and the doping ion contents do not influence the crystal structure. The excitation and emission spectra of samples were measured. The dependence of photoluminescence intensity and lifetime of level on Eu3+ concentration and synthesis temperature of samples are also discussed. PMID- 20355660 TI - Synthesis and luminescent properties of Eu(3+)-doped NaCaPO4 nano-particles under VUV-UV excitation. AB - A red emitting phosphor, Eu(3+)-doped NaCaPO4, has been prepared by the sol-gel method. X-ray powder diffraction (XRD) analyses confirmed the pure crystalline phase of NaCaPO4. The morphologies of the phosphor were investigated by scanning electron microscopy (SEM), which indicated that the phosphor had a good quality of surface crystallization. This phosphor had the grain sizes of around 500 nm with fairly narrow size distribution. The vacuum ultraviolet (VUV) synchrotron radiation spectroscopy technique was used to study the luminescence properties of this phosphor. The excitation spectra revealed that there is an efficient energy transfer from the phosphate host to Eu3+ ions. Upon excitation with VUV and UV radiation, the phosphor showed strong red emission around 618 nm corresponding to the forced electric dipole 5D0 --> 7F2 transition of Eu3+ ions. Defects and micro structures that related to Eu3+ ions in the phosphate host are discussed. PMID- 20355661 TI - Solvothermal synthesis and photoluminescence properties of ZnS:Mn2+/ZnO core shell nanocrystals. AB - High-quality ZnS:Mn2+ and ZnS:Mn2+/ZnO core-shell nanocrystals (NCs) were synthesized via a solvothermal method, and characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) and photoluminescence (PL) spectra. Compared with the bare ZnS:Mn2+ NCs (10 nm), the obtained ZnS:Mn2+/ZnO core-shell NCs have a smaller size (4 nm) and better dispersion, which could be attributed to the added ammonia that adsorbed on the surface of ZnS nuclei and hindered their further growth. From the PL spectrum of ZnS:Mn2+NCs, orange luminescence at about 595 nm is observed, which is attributed to the 4T1-6A1 transition of the Mn2+. Meanwhile, the PL intensity of the ZnS:Mn2+/ZnO core-shell NCs is enhanced, and the emission peak is shifted from 595 to 581 nm. The enhancement of the PL intensity is due to the elimination of the surface defects after the growth of the ZnO shell on ZnS:Mn2+ NCs, while the peak blue shift is mainly ascribed to the stress from the mismatch of lattice constants between ZnS and ZnO NCs. PMID- 20355662 TI - Preparation and visible light photocatalytic activity of N-doped titania. AB - N-doped titania powders were prepared with titanium tetraisopropoxide (TTIP) as the titanium source and urea as the nitrogen source by the sol-gel method. The samples were characterized using X-ray diffraction (XRD), diffuse reflectance spectrum (DRS), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). The XRD and TEM results indicated that urea played an important role in controlling the size and aggregation process of titania nanoparticles. As an appropriate amount of urea was added into the titania sol, the size of the particles decreased. However, the excess urea reduced the dispersion of the particles and resulted in the aggregation. At the same time, the size of particle increased, and the size distribution broadened. The XPS and DRS results showed that the nitrogen was incorporated into titania lattice successfully, which brought about the redshift of the absorption edge and induced the photocatalytic activity in the visible light region. The photocatalytic experiments showed that the N-doped titania nanoparticles could effectively photodegrade methyl orange (MO) aqueous solution under visible light irradiation. The photocatalytic activity increased with the increase of the nitrogen doping level in the titania lattice, but decreased with the increase of the particle size and the organic surface residues caused by excess urea. PMID- 20355663 TI - Investigation of radiative and nonradiative relaxation by two-photon resonant excitation in Tm3+ doped LaF3 particles. AB - Nano-scaled and micro-scaled Tm(3+)-doped LaF3 were prepared by a hydrothermal technique. Two-photon resonant excitation from the ground state 3H6 to the excited state 1D2 was fulfilled by two pulsed dye lasers tuned at 656 nm and 643 nm, respectively, which were resonant with the ground state absorption of 3H6 --> 3F2 and the excited state absorption of 3H4 --> 1D2. The time evolution of the corresponding state was investigated with blue upconverted emission by tuning the delay of two excitation lights. The results showed that the nonradiative relaxation of the 3F2 state was mainly affected by the confinement effect, while the radiative relaxation of 3H4 state was significantly influenced by the Tm3+ concentration. PMID- 20355664 TI - Enhanced Raman scattering in slow-light photonic crystals for chip-scale frequency conversion and optical amplification. AB - We present measurements of enhanced Raman scattering in silicon slow-light photonic crystal waveguides. By utilizing both the Bragg gap edge dispersion of TM-like modes for pump enhancement and the TE-like fundamental mode onset for Stokes enhancement, a six-fold increase in the spontaneous Raman scattering was observed in the double slow-light regime. Both forward and backward Stokes signals are examined, with continuous-wave measurements, in our low-loss photonic crystal membranes. The measured nonlinear enhancement matches well with our numerical model and simulations, and are described in detail in this paper. These observations support the development of chip-scale frequency conversion and optical amplification in silicon nanophotonics. PMID- 20355665 TI - Remarkable differences in photoluminescence properties between BaF2:Eu3+ microrods and nanorods. AB - The preparation process and photoluminescent properties of one-dimensional BaF2:Eu3+ nanorods (NRs) and microrods (MRs) were investigated. The results indicate that the samples were NRs with uniform diameters in the range of 30-50 nm, and lengths in the range of 1.2-3 microm when cooled to room temperature naturally. However, the samples were MRs with length of 1.5-3.0 microm and outer diameters of 200-250 nm when cooled to room temperature immediately. Furthermore, the relative intensity of 5D0 --> 7F2 depended on the two structures obtained under different temperatures. This work demonstrates that a MRs may be more favorable than NRs for photoluminescence. PMID- 20355666 TI - Selective assembly of multi-component nanosprings and nanorods. AB - This communication proposes a new approach to create complex hierarchical nano-to meso-scale architectures based on the use of biological connector molecules to direct the assembly of uniquely shaped multi-component nanostructures fabricated using glancing angle deposition (GLAD). Multiple sets of 50-nm-wide and 150 to 650-nm-tall Si-Cr/Au multi-stack zigzag nanosprings and nanorods are grown by GLAD on Si substrates. Nanorods, chosen for selective assembly, are detached from the substrate, suspended in an aqueous solution, and their surfaces are selectively functionalized by attaching biotin and streptavidin connector molecules to the Au-regions. Successive mixing of different suspensions leads to the end-to-end assembly of long and short nanorods. This technique provides the path to build hybrid nano-architectures including nano-honeycombs, nanoladders, and 3D nanorod networks, comprised of controlled material combinations. PMID- 20355667 TI - A large quantity synthesis of ultra-thin ZnO nanobelts induced from stacking faults. AB - Thin ZnO nanobelts with average width of 7.5 nm have been synthesized using vapor phase transport method. It was found that stacking faults directed the growth of the thin nanobelts along the (0110) direction with {2110} top/bottom surfaces and {0001} side surfaces. The {0002} stacking fault with translation of 1/3(0110) extends throughout entire length of the ZnO nanobelts. The growth steps at the {0110} growth fronts resulted from the {0002} stacking fault are believed to direct fast axial growth of the thin ZnO nanobelts. The thin ZnO nanobelts are expected to be promising candidates for highly sensitive chemical and biological sensor applications. PMID- 20355668 TI - [Persistent interactions]. PMID- 20355669 TI - [Pediatric pharmacy]. PMID- 20355670 TI - [Extra- and paravasation of cytotoxic drugs. Pathomechanisms and current preventive measures]. AB - Defined anticancer drugs are able to induce severe local damages in cases of accidental extravasation. The underlying pathomechanisms differ from each other, e.g. vincristine and conventional doxorubicin, when the corresponding intervention needs hyaluronidase and dexrazoxane, respectively. Whether an intensified diagnostic measure may help to assume extent and severity of local drug extravasation more accurately, needs further clinical investigation. PMID- 20355671 TI - [Treatment-acquired illness: drug side effects in the gastrointestinal tract]. PMID- 20355672 TI - [Is breast feeding by the mother under lamotrigine therapy feasible? ]. PMID- 20355673 TI - Symphysiotomy--a randomized controlled trial now overdue. PMID- 20355674 TI - Retrospective study from Harare Central Maternity Hospital comparing symphysiotomies with Caesarean Sections for similar indications. AB - OBJECTIVE: To explore the possibility that in obstructed labour with a live baby, a delivery by symphysiotomy is an ethical option. DESIGN: Retrospective cohort study. SETTING: Teaching hospital with busy maternity wards. SUBJECTS: Women in (nearly) second stage obstructed labour who were either delivered by Caesarean Section (79), or symphysiotomy, (172). MAIN OUTCOME MEASURES: Comparing perinatal mortality and morbidity and maternal complications, pain, long term morbidity and subsequent reproductive behaviour. RESULTS: There is no evidence of more foetal mortality or morbidity after a symphysiotomy. Short term maternal morbidity is more serious after Caesarean Section. Long term maternal morbidity might be increased after symphysiotomies, compared with Caesarean Section. Because there are more repeat operative deliveries and trials of scar after a Caesarean Section, future maternal, foetal and infant mortality is higher. CONCLUSION: Rejection of symphysiotomies as an option for delivery in cases of obstructed labour is not evidence based. It is very likely that lives could be saved if symphysiotomies were taught in the sub-Saharan teaching hospitals and practiced in the district hospitals. Those who oppose symphysiotomies should provide the relevant data. PMID- 20355675 TI - Urinary iodine excretion in pregnant women as an index of the impact of a national iodization programme. AB - OBJECTIVE: To evaluate the extent to which increase in iodine requirement was achieved in pregnant women who attended the antenatal clinic at Harare Central Hospital. DESIGN: Cross sectional. SETTING: Samples were collected from pregnant women attending antenatal clinic at Harare Central Hospital, and from lactating mothers and their infants. SUBJECTS: 100 pregnant women attending the antenatal clinic at Harare Central hospital, 80 infants, 80 lactating women and 18 non pregnant women. MAIN OUTCOME MEASURES: Comparison of urinary iodine excretion levels among pregnant women, lactating mothers and their infants. RESULT: The results indicated lower urinary iodine excretion levels for the pregnant women and lactating mothers compared to the urinary iodine excretion of the infants and the breast milk iodine content. The urinary iodine excretion level of the non pregnant control women was median (first and third quartiles): 18.5 microg/dl (30.0, 30.2 microg/dl). The urinary iodine excretion level of the lactating mothers was median (first and third quartiles): 12.0 mg/dl (7.6, 19.5 mg/dl) compared to the level of the infants, median (first and third quartiles): 26.5 mg/dl (18.8, 11.5 mg/dl). A significant difference was noted between the median urinary iodine excretion levels of the mothers, and the median levels of the infants, p = 0.001. The mean milk iodine content was 21.2 +/- 6.8 mg/dl. There was no correlation between breast milk iodine levels and the urinary iodine excretion levels of the infants, (p = 0.96, r = 0.006). Positive correlation was found between maternal urinary iodine excretion levels and the urinary iodine excretion levels of the infants, p = 0.016 r = 0.285. Serum FT4, and TSH levels were found to be higher for infants at six weeks after birth, (FT4 =20.91 +/- 5.65 pmol/L) and median TSH = 2.28 mIU/ml (1.36, 0.86) mIU/rnl, compared to levels at 12 weeks postpartum: (FT4 = 17.53-*6.4 pmol/L) and median TSH = 2.02 mIU/ml, (0.84, 1.55) mIU/ml. The differences were not significant. CONCLUSION: The results indicated a significant reduction in the urinary iodine content of pregnant women, and lactating mothers which did not appear to have any relationship to the urinary iodine excretion levels of infants and iodine content of breast milk. Iodine intake needed to be raised to reflect the recent proposed recommendations. PMID- 20355676 TI - Infection control among dental therapists in Zimbabwe. AB - OBJECTIVES: To assess the general infection control practices with special reference to the prevention of transmission of HIV/AIDS infection among dental therapists in Zimbabwe. SETTING: Dental therapists practising in Zimbabwe Government Oral Health Clinics. METHODS: A descriptive cross sectional study using a self-administered questionnaire. Questions dealt with infection control practices in the procedure rooms, including barriers to transmission of infection, the practice of disinfection of working surfaces, the use of autoclave, and sterilization of the handpiece. The questionnaire also covered issues of personal protection through the use of protective wear, vaccination against hepatitis B as well as knowledge of one's HIV status. RESULTS: There was a 68% (24/35) response rate. The therapists were predominantly male and they were evenly distributed in the provinces of Zimbabwe. All were trained in Zimbabwe; 91.7% had not been vaccinated against hepatitis B and only 20% (n = 7) had undergone previous HIV testing. Use of gloves was universal; 92% used face masks; 66.7% used protective eyewear; 87.5% wore protective garments; 95% autoclaved/chemoclaved high speed handpieces; 83.3% autoclaved/chemoclaved slow speed handpieces. Barriers to infection control ranged from 22.7% to 40.9% and was attributed to non-availability of gloves and disinfectants. CONCLUSION: The dental therapists seem to practise acceptable infection control methods. There is need to improve upon handpiece sterilization, the use of eyewear and improvement upon supplies for disinfection. Vaccination against hepatitis B virus needs to be encouraged. PMID- 20355677 TI - Harare doctors support the need for training in basic business and economics principles in medical school: a pilot study. PMID- 20355678 TI - Compliance and loss to follow up of HIV negative and positive mothers recruited from a PMTCT programme in Zimbabwe. AB - OBJECTIVE: To describe the methodological challenges of a nine months follow up study of mothers recruited from a national Prevention of Mother To Child Transmission (PMTCT) programme with regards to defaulters, drop outs and compliance. DESIGN: Nested case control study. SETTING: Three peri-urban clinics in Zimbabwe namely: Epworth, St Mary's, Seke North. METHOD: Pregnant women who enrolled at 36 weeks of gestation were recruited for a follow up of mother and child from delivery, six weeks, four and nine months post partum. Follow up trend of these women was compared between the HIV positive and negative mothers with regards to defaulting, drop outs, full and partial compliance. Statistical significance was computed using the Chi-square test. RESULTS: Of the enrolled 1050 pregnant women with a known HIV status (594 HIV negative and 456 HIV positive) 851 (457 HIV negative and 394 HIV positive) showed up at one or more visits scheduled up to nine months. The denominator was dropping at each point and time. The overall dropout rate was 19% without a significant difference between the HIV positive and negative women at delivery. At six weeks the drop out rate was 35 (7.7%) for the HIV positive versus 75 (12.9%) p=0.010 and at four months 12 (2.9%) versus 39 (7.7%) p=0.002 respectively. However, at nine months the drop out rate was not different (p=0.747). The defaulter rate was significantly different at every stage between the HIV positive and negative mothers from delivery to six weeks, becoming even more significant at the four and nine months visit (p=<0.001). The overall full compliance at nine months was 46.1% with a significant difference between the HIV positive (55.6%) versus (37.9%) for the HIV negative (p=<0.001). CONCLUSION: Drop out is highest among the HIV negative as opposed to the HIV positive with the peak period being at "six weeks". There is high defaulting among the HIV negative compared to the HIV positive with the peak being at "four months". The study has shown that the HIV negative women are more likely to drop out whereas the HIV positive were twice as likely to fully comply. It is surprising that the peak drop out period, "six weeks visit" is a cardinal existing national scheduled visit where both mother and baby undergo a full medical examination with the mother having a pap smear taken. PMID- 20355679 TI - The levels of malnutrition and risk factors for mortality at Harare Central Hospital-Zimbabwe: an observation study. AB - OBJECTIVES: To determine the prevalence of malnutrition, and identify risk factors associated with mortality in acute severe malnutrition in a major referral hospital in Harare. DESIGN: Cross sectional analytical study. SETTING: Harare Central Hospital, paediatric wards. SUBJECTS: All children admitted to the general paediatric medical wards between 12 October 2003 and 19 January 2004 were surveyed. MAIN OUTCOME MEASURES: Prevalence and mortality in hospitalized children with acute severe malnutrition. STUDY FACTORS: Patient's age, sex, vaccination status, type of malnutrition, weight-for-height, breast feeding status (age <24 months), care giver details, orphanage, area of residence, new or re-admission, time of admission, admission temperature, co-morbidity conditions, HIV status and selected laboratory tests. RESULTS: A total of 784 infants and children were admitted during the study period, of whom 619 were eligible for the study. Of the 619 children, 259 (41.8%) had acute severe malnutrition, 79 (12.8%) moderate malnutrition and 281 (45.5%) had no malnutrition. Fatality rates were 42.9% (acute severe malnutrition), 32.9% (moderate malnutrition), and 21% (no malnutrition) respectively. Factors predictive of mortality by multivariate analysis were age <18 months (O.R=2.27; 95% CI 1.20-4.29), weight-for-height <70% (O.R=2.63; 95% CI=1.24-5.56), acute diarrhoea (O.R=3.42; 95% CI=1.53-7.65), persistent diarrhoea (O.R=2.67; 95% CI= 1.26-5.66), and pneumonia (O.R=2.21; 95% CI= 1.08-4.52). CONCLUSION: Mortality among children with acute severe malnutrition at this institution was unacceptably high. Case management needs strengthening particularly for malnutrition, diarrhoea and pneumonia. The role of high HIV prevalence rates on mortality in this population needs evaluating. PMID- 20355680 TI - Acute renal failure (ARF) in developing countries: which factors actually influence survival. AB - Acute renal failure, a relatively common clinical condition, is still associated with a high mortality rate in both developed and developing countries despite the differences in the epidemiology, clinical characteristics and therapeutic modalities offered to affected patients. The various modalities of renal replacement therapy are still largely inaccessible, unaffordable and unavailable in most parts of sub-Saharan Africa, hence the need to judiciously utilise available resources. Consequently we studied patients with acute renal failure to critically appraise the factors that influence survival and determine the usefulness or otherwise of available renal replacement therapies (Acute HD and Acute PD). A total of 46 (34 (73.9%) males and 12 (26.1%) females) patients satisfied the inclusion criteria. Their ages ranged between 15 and 76 years (mean +/- SD; 38.2 +/-16.3 years). The commonest causes were gastro-enteritis (cholera) and septicaemia in 36.9% and 30.5% respectively. Twenty six (56.5%) of all the patients survived while the remaining 20 (43.5%) died. Twenty four (52.2%) patients had different complications of which pulmonary oedema was singularly found to significantly influence survival. Other factors that were found to significantly influence survival included availability of renal replacement therapy, the aetiology of ARF; gender; age of the patients and the duration of oliguria. We further compared the patients managed with haemodialysis with those managed with peritoneal dialysis and found no difference(s) in the age; duration of oliguria or hospitalisation; survival figures; effect of pulmonary oedema and the aetiology of ARF. However, the number of sessions for HD and the duration of PD significantly influenced survival. We conclude that ARF is still associated with a high mortality rate and prompt institution of available renal replacement therapy and aggressive management of complications would assist in reducing the trend. PMID- 20355681 TI - An integrative approach to health. AB - In this article, I make the case for using an integrative approach to health, broadly defined as social, emotional, mental, and physical well-being; for studying health among the young as an important marker for future health and well being across the life course; and for understanding health disparities among the young as both causes and consequences of social stratification. An integrative approach bridges biomedical sciences with social and behavioral sciences by understanding the linkages between social, behavioral, psychological, and biological factors in health. It is furthermore vital that integration occur in all steps of the research process: in theory, design, data collection, and analysis. I use the National Longitudinal Study of Adolescent Health, or Add Health, as an example of an integrative approach to health and of the importance of adolescence and the transition to adulthood years for setting health trajectories into adulthood. Evidence is also presented on the linkages between health trajectories during adolescence and the transition to adulthood and social stratification in adulthood. PMID- 20355682 TI - Early life exposures and the occurrence and timing of heart disease among the older adult Puerto Rican population. AB - Few studies have examined the effects of early life conditions on the timing of the onset of heart disease. We use the remarkable example of a representative sample of the population of older Puerto Ricans aged 60-74 who lived in the countryside during childhood (n = 1,438) to examine the effects ofseasonal exposures to poor nutrition and infectious diseases during late gestation on the timing of the onset and the probability of ever experiencing adult heart disease. Cox and log logistic hazard models controlling for childhood conditions (self reported childhood health status and socioeconomic status [SES], rheumatic fever, and knee height) and adult risk factors (adult SES, obesity, smoking, exercise, and self-reported diabetes) showed that the risk of onset of heart disease was 65% higher among those born during high-exposure periods compared with unexposed individuals. However, there were no significant differences in median time of onset for those ever experiencing heart disease. As a comparison, we found that there were no significant seasonality effects for those who lived in urban areas during childhood. We conclude that early exposures in utero have important ramifications for adult heart disease among the older Puerto Rican population. We show, however, that while exposure is associated with the probability of ever experiencing adult heart disease, it is not associated with the timing of onset among those who do experience it. PMID- 20355683 TI - Health, wartime stress, and unit cohesion: evidence from Union Army veterans. AB - We find that Union Army veterans of the American Civil War who faced greater wartime stress (as measured by higher battlefield mortality rates) experienced higher mortality rates at older ages, but that men who were from more cohesive companies were statistically significantly less likely to be affected by wartime stress. Our results hold for overall mortality, mortality from ischemic heart disease and stroke, and new diagnoses of arteriosclerosis. Our findings represent one of the first long-run health follow-ups of the interaction between stress and social networks in a human population in which both stress and social networks are arguably exogenous. PMID- 20355684 TI - Facing up to uncertain life expectancy: the longevity fan charts. AB - This article uses longevity fan charts to represent the uncertainty in projections of future life expectancy. These fan charts are based on a mortality model calibrated on mortality data for English and Welsh males. The fan charts indicate strong upward sloping trends in future life expectancy. Their widths indicate the extent of uncertainty in these projections, and this uncertainty increases as the forecast horizon lengthens. Allowing for uncertainty in the parameter values of the model adds further to uncertainty in life expectancy projections. The article also illustrates how longevity fan charts can be used to stress-test longevity outcomes. PMID- 20355685 TI - Obesity and excess mortality among the elderly in the United States and Mexico. AB - Increasing levels of obesity could compromise future gains in life expectancy in low- and high-income countries. Although excess mortality associated with obesity and, more generally, higher levels of body mass index (BAI) have been investigated in the United States, there is little research about the impact of obesity on mortality in Latin American countries, where very the rapid rate of growth of prevalence of obesity and overweight occur jointly with poor socioeconomic conditions. The aim of this article is to assess the magnitude of excess mortality due to obesity and overweight in Mexico and the United States. For this purpose, we take advantage of two comparable data sets: the Health and Retirement Study 2000 and 2004 for the United States, and the Mexican Health and Aging Study 2001 and 2003 for Mexico. We find higher excess mortality risks among obese and overweight individuals aged 60 and older in Mexico than in the United States. Yet, when analyzing excess mortality among different socioeconomic strata, we observe greater gaps by education in the United States than in Mexico. We also find that although the probability of experiencing obesity-related chronic diseases among individuals with high BMI is larger for the U.S. elderly, the relative risk of dying conditional on experiencing these diseases is higher in Mexico. PMID- 20355686 TI - Multivariate analysis of parity progression-based measures of the total fertility rate and its components. AB - This article describes a methodology for applying a discrete-time survival model the complementary log-log model-to estimate effects of socioeconomic variables on (1) the total fertility rate and its components and (2) trends in the total fertility rate and its components. For the methodology to be applicable, the total fertility rate (TFR) must be calculated from parity progression ratios (PPRs). The components of the TFR are PPRs, the total marital fertility rate (TMFR), and the TFR itself as measures of the quantum of fertility, and mean and median ages at first marriage and mean and median closed birth intervals by birth order as measures of the tempo or timing of fertility. The focus is on effects of predictor variables on these measures rather than on coefficients, which are often difficult to interpret in the complex models that are considered. The methodology is applicable to both period and cohort data. It is illustrated by application to data from the 1993, 1998, and 2003 Demographic and Health Surveys (DHS) in the Philippines. PMID- 20355687 TI - Childhood nutrition and later fertility: pathways through education and pre pregnant nutritional status. AB - Better childhood nutrition is associated with earlier physical maturation during adolescence and increased schooling attainment. However, as earlier onset of puberty and increased schooling can have opposing effects on fertility, the net effect of improvements in childhood nutrition on a woman's fertility are uncertain. Using path analysis, we estimate the strength of the pathways between childhood growth and subsequent fertility outcomes in Guatemalan women studied prospectively since birth. Height for age z score at 24 months was positively related to body mass index (BMI kg/m2) and height (cm) in adolescence and to schooling attainment. BMI was negatively associated (-0.23 +/- 0.09 years per kg/m2; p < .05) and schooling was positively associated (0.38 +/- 0.06 years per grade; p < .001) with age at first birth. Total associations with the number of children born were positive from BMI (0.07 +/- 0.02 per kg/m2; p < .05) and negative from schooling (-0.18 +/- 0.02 per grade; p < .01). Height was not related to age at first birth or the number of children born. Taken together, childhood nutrition, as reflected by height at 2 years, was positively associated with delayed age at first birth and fewer children born. If schooling is available for girls, increased growth during childhood will most likely result in a net decrease infertility. PMID- 20355688 TI - Endowments and parental investments in infancy and early childhood. AB - This article tests whether parents reinforce or compensate for child endowments. We estimate how the difference in birth weight across siblings impacts specific parental investments: breast-feeding, well-baby visits, immunizations, and preschool attendance. Our results indicate that normal-birthweight children are 5%-11% more likely to receive early childhood parental investments than their low birth-weight siblings. Moreover, the presence of additional low-birth-weight siblings in the household increases the likelihood of investments such as well baby visits and immunizations for normal-birth-weight children. These results suggest that parental investments in early childhood tend to reinforce endowment differences. PMID- 20355689 TI - Orphanhood and human capital destruction: is there persistence into adulthood? AB - This article presents unique evidence that orphanhood matters in the long run for health and education outcomes in a region of northwestern Tanzania. We study a sample of 718 non-orphaned children surveyed in 1991-1994 who were traced and reinterviewed as adults in 2004. A large proportion, 19%, lost one or more parents before age 15 in this period, allowing us to assess permanent health and education impacts of orphanhood. In the analysis, we control for a wide range of child and adult characteristics before orphanhood, as well as community fixed effects. We find that maternal orphanhood has a permanent adverse impact of 2 cm of final height attainment and one year of educational attainment. Expressing welfare in terms of consumption expenditure, the result is a gap of 8.5% compared with similar children whose mothers survived until at least their 15th birthday. PMID- 20355690 TI - Parenting as a "package deal": relationships, fertility, and nonresident father involvement among unmarried parents. AB - Fatherhood has traditionally been viewed as part of a "package deal" in which a father's relationship with his child is contingent on his relationship with the mother. We evaluate the accuracy of this hypothesis in light of the high rates of multiple-partner fertility among unmarried parents using the Fragile Families and Child Wellbeing Study, a recent longitudinal survey of nonmarital births in large cities. We examine whether unmarried mothers' and fathers' subsequent relationship and parenting transitions are associated with declines in fathers' contact with their nonresident biological children. We find that father involvement drops sharply after relationships between unmarried parents end. Mothers 'transitions into new romantic partnerships and new parenting roles are associated with larger declines in involvement than fathers' transitions. Declines in fathers' involvement following a mother's relationship or parenting transition are largest when children are young. We discuss the implications of our results for the well-being of nonmarital children and the quality of nonmarital relationships faced with high levels of relationship instability and multiple-partner fertility. PMID- 20355691 TI - Patterns of nonresident father contact. AB - We used the National Longitudinal Survey of Youth 1979 cohort (NLSY79) from 1979 to 2002 and the Children of the National Longitudinal Survey of Youth (CNLSY) from 1986 to 2002 to describe the number, shape, and population frequencies of U.S. nonresident father contact trajectories over a 14-year period using growth mixture models. The resulting four-category classification indicated that nonresident father involvement is not adequately characterized by a single population with a monotonic pattern of declining contact over time. Contrary to expectations, about two-thirds of fathers were consistently either highly involved or rarely involved in their children's lives. Only one group, constituting approximately 23% of fathers, exhibited a clear pattern of declining contact. In addition, a small group of fathers (8%) displayed a pattern of increasing contact. A variety of variables differentiated between these groups, including the child's age at father-child separation, whether the child was born within marriage, the mother's education, the mother's age at birth, whether the father pays child support regularly, and the geographical distance between fathers and children. PMID- 20355692 TI - Last hired, first fired? Black-white unemployment and the business cycle. AB - Studies have tested the claim that blacks are the last hired during periods of economic growth and the first fired in recessions by examining the movement of relative unemployment rates over the business cycle. Any conclusion drawn from this type of analysis must be viewed as tentative because cyclical movements in the underlying transitions into and out of unemployment are not examined. Using Current Population Survey data matched across adjacent months from 1989-2004, this article provides the first detailed examination of labor market transitions for prime-age black and white men to test the last hired, first fired hypothesis. Considerable evidence is presented that blacks are the first fired as the business cycle weakens. However no evidence is found that blacks are the last hired. Instead, blacks appear to be initially hired from the ranks of the unemployed early in the business cycle and later are drawn from nonparticipation. The narrowing of the racial unemployment gap near the peak of the business cycle is driven by a reduction in the rate of job loss for blacks rather than increases in hiring. PMID- 20355693 TI - Education and gender bias in the sex ratio at birth: evidence from India. AB - This article investigates the possible existence of a nonlinear link between female disadvantage in natality and education. To this end, we devise a theoretical model based on the key role of social interaction in explaining people's acquisition of preferences, which justifies the existence of a nonmonotonic relationship between female disadvantage in natality and education. The empirical validity of the proposed model is examined for the case of India, using district-level data. In this context, our econometric analysis pays particular attention to the role of spatial dependence to avoid any potential problems of misspecification. The results confirm that the relationship between the sex ratio at birth and education in India follows an inverted U-shape. This finding is robust to the inclusion of additional explanatory variables in the analysis, and to the choice of the spatial weight matrix used to quantify the spatial interdependence between the sample districts. PMID- 20355694 TI - Development of a novel Submerged Membrane Electro-Bioreactor (SMEBR): performance for fouling reduction. AB - A novel Submerged Membrane Electro-Bioreactor (SMEBR) was developed to treat wastewater and control the problem of membrane fouling. To validate the new design, experimental work was achieved in a few phases. This paper describes the design constraints and criteria of the new developed SMEBR system, and shows the results of the performance of the SMEBR system to reduce membrane fouling when intermittent direct current (DC) (15 min ON/45 min OFF) was applied using cylindrical iron mesh for both electrodes. Application of the SMEBR system enhanced the membrane filterability by reducing the fouling rate up to 16.3% without any backwashing of the membrane module. The improvement in membrane filterability associated with a decrease in zeta potential of the mixed liquor flocs from -30.5 up to -15.3 mV and a decrease in specific resistance to filtration (SRF) up to 40% was observed. PMID- 20355695 TI - Greenhouse gas and carbon profile of the u.s. Forest products industry value chain. AB - A greenhouse gas and carbon accounting profile was developed for the U.S. forest products industry value chain for 1990 and 2004-2005 by examining net atmospheric fluxes of CO(2) and other greenhouse gases (GHGs) using a variety of methods and data sources. Major GHG emission sources include direct and indirect (from purchased electricity generation) emissions from manufacturing and methane emissions from landfilled products. Forest carbon stocks in forests supplying wood to the industry were found to be stable or increasing. Increases in the annual amounts of carbon removed from the atmosphere and stored in forest products offset about half of the total value chain emissions. Overall net transfers to the atmosphere totaled 91.8 and 103.5 TgCO(2)-eq. in 1990 and 2005, respectively, although the difference between these net transfers may not be statistically significant. Net transfers were higher in 2005 primarily because additions to carbon stored in forest products were less in 2005. Over this same period, energy-related manufacturing emissions decreased by almost 9% even though forest products output increased by approximately 15%. Several types of avoided emissions were considered separately and were collectively found to be notable relative to net emissions. PMID- 20355696 TI - Application of an optimized total N-nitrosamine (TONO) assay to pools: placing N nitrosodimethylamine (NDMA) determinations into perspective. AB - Although N-nitrosodimethylamine (NDMA) has been the most prevalent N-nitrosamine detected in disinfected waters, it remains unclear whether NDMA is indeed the most significant N-nitrosamine or just one representative of a larger pool of N nitrosamines. A widely used assay applied to quantify nitrite, S-nitrosothiols, and N-nitrosamines in biological samples involves their reduction to nitric oxide by acidic tri-iodide, followed by chemiluminescent detection of the evolved nitric oxide in the gas phase. We here describe an adaptation of this method for analyzing total N-nitrosamine (TONO) concentrations in disinfected pools. Optimal sensitivity for N-nitrosamines was obtained using a reduction solution containing 13.5 mL glacial acetic acid and 1 mL of an aqueous 540 g/L iodide and 114 g/L iodine solution held at 80 degrees C. The method detection limit for N nitrosamines was 110 nM using 100 microL sample injections and NDMA as a standard. N-nitrosamines featuring a range of polarities were converted to nitric oxide with 75-103% efficiency compared to NDMA. Evaluation of potential interfering species indicated that only nitrite and S-nitrosothiols were a concern, but both interferences were effectively eliminated using group-specific sample pretreatments previously employed for biological samples. To evaluate the low TONO concentrations anticipated for pools, 1 L samples were extracted by continuous liquid-liquid extraction with ethyl acetate for 24 h, and concentrated to 1 mL. N-nitrosamine recovery during extraction ranged from 37-75%, and there was a potential for artifactual nitrosation of amines during solvent reflux in the presence of significant nitrite concentrations, but not at the low nitrite concentrations prevalent in most pools. Using the 1000-fold concentration factor and 56% average extraction efficiency, the method detection limit would be 62 pM (5 ng/L as NDMA). The TONO assay was applied to six pools and their common tap water source in conjunction with analysis for specific nitrosamines. Even accounting for the range of N-nitrosamine extraction recoveries, NDMA accounted for an average of only 13% (range 3-46%) of the total nitrosamine pool. PMID- 20355697 TI - Biodegradation of polyfluoroalkyl phosphates as a source of perfluorinated acids to the environment. AB - Wastewater treatment plants (WWTPs) have been identified as a major source of perfluorocarboxylates (PFCAs) to aqueous environments. The observed increase in PFCA mass flows from WWTP influent to effluent suggests the biodegradation of commercial fluorinated materials within the WWTP. Commercial fluorinated surfactants are used as greaseproofing agents in food-contact paper products as well as leveling and wetting agents. As WWTPs are likely the major fate of these surfactants, their biodegradation may be a source of PFCA production. One class of commercial surfactants, the polyfluoroalkyl phosphates (PAPs), have been observed in WWTP sludge. While PAPs have been shown to degrade into PFCAs in a rat model, the present study investigates their microbial fate to determine whether the biodegradation of PAPs within a WWTP-simulated system will contribute to the load of PFCAs released. PAPs are applied commercially in mixed formulations of different chain lengths and substitution at the phosphate center. The effect of chain length and phosphate substitution on the biodegradation of PAPs was investigated by incubating mixtures of 4:2, 6:2, 8:2, and 10:2 monosubstituted PAPs (monoPAPs) in an aerobic microbial system and by separately incubating the 6:2 monoPAP and 6:2 disubstituted PAP (diPAP) for 92 days. Headspace sampling revealed production of the fluorotelomer alcohols (FTOHs) from the hydrolysis of the PAP phosphate ester linkages. Analysis of the aqueous phase revealed microbial transformation of the PAPs to the final PFCA products was possible. The majority of the oxidation products observed were consistent with previous investigations that have suggested fluorotelomer precursor compounds degrade predominantly via a beta-oxidation-like mechanism. However, in this study, the detection of odd-chain PFCAs suggests that other pathways may be important. The present study demonstrated microbially mediated biodegradation of PAPs to PFCAs. This observation, together with the diPAP concentrations observed in WWTP sludge, suggest PAPs-containing commercial products may be a significant contributor to the increased PFCA mass flows observed in WWTP effluents. PMID- 20355698 TI - Planar tetracoordinate carbon strips in edge decorated graphene nanoribbon. AB - We predicted highly stable Cu-decorated zigzag graphene nanoribbons (ZGNRs) containing planar tetracoordinate carbon (ptC) strip(s). The computed electronic band structures suggest that the Cu-decorated ZGNRs are semiconducting. The Hirshfeld spin analysis suggests significant spin distribution at the edge ptC atoms. The two ptC strips are antiferromagnetically coupled, even though the edge Cu atoms do not exhibit significant magnetism. The stability of the multicenter ptC strip stems from both the highly delocalized pi orbital of ZGNRs and nearly perfect match between Cu-Cu bonding geometries and carbon atoms at the ZGNR edges. PMID- 20355699 TI - Energetic decomposition with the generalized-born and Poisson-Boltzmann solvent models: lessons from association of G-protein components. AB - Continuum electrostatic models have been shown to be powerful tools in providing insight into the energetics of biomolecular processes. While the Poisson Boltzmann (PB) equation provides a theoretically rigorous approach to computing electrostatic free energies of solution in such a model, computational cost makes its use for large ensembles of states impractical. The generalized-Born (GB) approximation provides a much faster alternative, although with a weaker theoretical framework. While much attention has been given to how GB recapitulates PB energetics for the overall stability of a biomolecule or the affinity of a complex, little attention has been given to how the contributions of individual functional groups are captured by the two methods. Accurately capturing these individual electrostatic components is essential both for the development of a mechanistic understanding of biomolecular processes and for the design of variant sequences and structures with desired properties. Here, we present a detailed comparison of the group-wise decomposition of both PB and GB electrostatic free energies of binding, using association of various components of the heterotrimeric-G-protein complex as a model. We find that, while net binding free energies are strongly correlated in the two models, the correlations of individual group contributions are highly variable; in some cases, strong correlation is seen, while in others, there is essentially none. Structurally, the GB model seems to capture the magnitude of direct, short-range electrostatic interactions quite well but performs more poorly with moderate-range "action-at-a distance" interactions--GB has a tendency to overestimate solvent screening over moderate distances, and to underestimate the costs of desolvating charged groups somewhat removed from the binding interface. Despite this, however, GB does seem to be quite effective as a predictor of those groups that will be computed to be most significant in a PB-based model. PMID- 20355700 TI - Nanoporous linear polyethylene from a block polymer precursor. AB - Porous polyolefin membranes play an integral role in lithium-ion battery technology as the barrier preventing direct anode and cathode contact. Block polymers containing a sacrificial component have proven to be attractive precursors for nanoporous polymer membranes stemming from their unique ability to self-assemble into mesoscopically organized structures. Selective removal of the sacrificial component can leave a scaffold with well-controlled pore dimensions and porosity. This communication describes the synthesis of block polymers containing polylactide (PLA) as the sacrificial component and perfectly linear polyethylene (LPE) as the matrix phase using a combination of ring-opening polymerizations. Bicontinuous morphologies accessible over a broad composition range allow for ready tailoring of porosity. Removal of the PLA results in semicrystalline LPE with an interpenetrating void space having pore dimensions less than 100 nm. The porosity and domain size dependence on composition was corroborated by nitrogen adsorption and scanning electron microscopy. The mechanical robustness of the nanoporous samples was confirmed by tensile testing. The outstanding chemical resistance of the nanoporous LPE samples was demonstrated by treatment with concentrated strong acids over extended periods (approximately 1 day). PMID- 20355701 TI - Extended triple layer modeling of arsenate and phosphate adsorption on a goethite based granular porous adsorbent. AB - The extended triple layer model (ETLM), which is consistent with spectroscopic and theoretical molecular evidence, is first systematically tested for its capability to model adsorption of arsenate and phosphate, a strong competitor, on a common goethite-based granular porous adsorptive media (Bayoxide E33 (E33)) in water treatment systems under a wide range of solution conditions. Deprotonated bidentate-binuclear, protonated bidentate-binuclear, and deprotonated monodentate complexes are chosen as surface species for both arsenate and phosphate. The estimated values of the ETLM parameters of arsenate for the adsorbent are close to those for pure goethite minerals previously determined by others. The ETLM predictions for arsenate and phosphate adsorption basically agree with experimental results over a wide range of pH, surface coverage, and solid concentrations. High background electrolyte concentration (i.e., I = 0.1 M), however, was found to strongly impact arsenate and phosphate adsorption on E33 probably because of the porous structure of the adsorbent, which cannot be observed for pure goethite minerals and could not be completely modeled by the ETLM. Prediction of phosphate adsorption isotherms at higher pH were relatively poor, and this may suggest searching for alternative surface species for phosphate. Since adsorption equilibrium constants of major coexisting ions encountered in water treatment systems for goethite minerals have been estimated by others, the application of ETLM theory to this common goethite-based adsorptive media will enable us to understand how those coexisting ions macroscopically and thermodynamically interact with arsenate and phosphate in the environment of adsorptive water treatment system in a way consistent with molecular and spectroscopic evidence. PMID- 20355702 TI - Oxidant generation and toxicity of size-fractionated ambient particles in human lung epithelial cells. AB - Exposure to ambient particulate matter (PM) is associated with respiratory and cardiovascular disease and lung cancer. In this study, we used size fractionated PM samples (3-7, 1.5-3, 0.95-1.5, 0.5-0.95, and <0.5 microm), collected at four contrasting locations (three urban sites, one remote background) in the UK with a Sierra-Andersen high volume cascade impactor. The H(2)O(2)-dependent oxidant generating capacity of the samples was determined by electron spin resonance with 5,5-dimethyl-1-pyrroline-N-oxide spin trapping. In A549 human lung epithelial cells, we determined the cytotoxicity of samples by LDH assay, and interleukin-8 (IL-8) release as an indicator of their inflammatory potency. Oxidative DNA damage was measured by the formamido-pyrimidine-glycosylase (fpg)-modified comet assay. Marked contrasts were observed for all endpoints. Remote background PM showed the lowest oxidant potential, was neither cytotoxic nor genotoxic and did not increase IL-8 release. For the other samples, effects were found to depend more on sampling location than on size fraction. PM collected at high-traffic locations generally showed the strongest oxidant capacity and toxicity. Significant correlations were observed between the oxidant generating potential and all toxicological endpoints investigated, which demonstrates that measurement of the oxidant generating potential by ESR represents a sensitive method to estimate the toxic potential of PM. PMID- 20355703 TI - Adsorbed polymer and NOM limits adhesion and toxicity of nano scale zerovalent iron to E. coli. AB - Nanoscale zerovalent iron (NZVI) is used for groundwater remediation. Freshly synthesized bare, i.e. uncoated NZVI is bactericidal at low mg/L concentration, but the impact of surface modifiers and aging (partial oxidation) on its bactericidal properties have not been determined. Here we assess the effect that adsorbed synthetic polymers and natural organic matter (NOM) and aging (partial oxidation) have on the bactericidal properties of NZVI to the gram-negative bacterium, Escherichia coli. Exposure to 100 mg/L of bare NZVI with 28% Fe(0) content resulted in a 2.2-log inactivation after 10 min and a 5.2-log inactivation after 60 min. Adsorbed poly(styrene sulfonate) (PSS), poly(aspartate) (PAP), or NOM on NZVI with the same Fe(0) content significantly decreased its toxicity, causing less than 0.2-log inactivation after 60 min. TEM images and heteroaggregation studies indicate that bare NZVI adheres significantly to cells and that the adsorbed polyelectrolyte or NOM prevents adhesion, thereby decreasing NZVI toxicity. The 1.8-log inactivation observed for bare NZVI with 7% Fe(0) content was lower than the 5.2-log inactivation using NZVI with 28% Fe(0) after 1 h; however, the minimum inhibitory concentration (MIC) after 24 h was 5 mg/L regardless of Fe(0) content. The MIC of PSS, PAP, and NOM coated NZVI were much higher: 500 mg/L, 100 mg/L, and 100 mg/L, respectively. But the MIC was much lower than the typical injection concentration used in remediation (10 g/L). Complete oxidation of Fe(0) in NZVI under aerobic conditions eliminated its bactericidal effects. This study indicates that polyelectrolyte coatings and NOM will mitigate the toxicity of NZVI for exposure concentrations below 0.1 to 0.5 g/L depending on the coating and that aged NZVI without Fe(0) is relatively benign to bacteria. PMID- 20355704 TI - Functional assessment of cross-linked porous gelatin hydrogels for bioengineered cell sheet carriers. AB - An efficient carrier for corneal endothelial cell therapy should deliver and retain the cell sheet transplants at the site of injury without causing adverse effects. Here we introduced a simple stirring process combined with freeze-drying (SFD1) method for the development of gelatin hydrogels with enlarged pore structure that can improve the aqueous humor circulation. Samples fabricated by air-drying (AD) or freeze-drying method were used for comparison. After cross linking with 1 mM 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC), the discs were investigated to assess their functionality. The simultaneous presence of ice crystals and gas bubbles resulted in large pore size (461 +/- 85 mum) and high porosity (48.0 +/- 1.9%) of SFD1 carriers. Among all of the samples studied, the SFD1 hydrogels showed the most appropriate swelling characteristics without squeezing effect on the anterior segment tissues of the eye. The enlarged pore structure also allowed carriers to contain the highest fraction of mobile water and exhibit the lowest resistance to the glucose permeation. In comparison with AD samples, the SFD1 materials had better cytocompatibility and biocompatibility and more effectively prevented a drastic change of intraocular pressure. Rheological measurements showed that the SFD1 hydrogels behaved like an elastic solid and had a tough (rigid and deformable) texture. As a temporary supporter, the biodegradable gelatin hydrogel could facilitate cell sheet transfer and avoid long-term residence of foreign carriers in the body. Our findings suggest that the gelatin discs with enlarged pore structure have potential as cell sheet carriers for intraocular delivery and corneal tissue engineering. PMID- 20355705 TI - Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties. AB - The objective of this work was to create 3D hydrogel matrices with defined mechanical properties as well as tunable degradability for use in applications involving protein delivery and cell encapsulation. Therefore, we report the synthesis and characterization of a novel hydrolytically degradable poly(ethylene glycol) (PEG) hydrogel composed of PEG vinyl sulfone (PEG-VS) cross-linked with PEG-diester-dithiol. Unlike previously reported degradable PEG-based hydrogels, these materials are homogeneous in structure, fully hydrophilic, and have highly specific cross-linking chemistry. We characterized hydrogel degradation and associated trends in mechanical properties, that is, storage modulus (G'), swelling ratio (Q(M)), and mesh size (xi). Degradation time and the monitored mechanical properties of the hydrogel correlated with cross-linker molecular weight, cross-linker functionality, and total polymer density; these properties changed predictably as degradation proceeded (G' decreased, whereas Q(M) and xi increased) until the gels reached complete degradation. Balb/3T3 fibroblast adhesion and proliferation within the 3D hydrogel matrices were also verified. In sum, these unique properties indicate that the reported degradable PEG hydrogels are well poised for specific applications in protein and cell delivery to repair soft tissue. PMID- 20355706 TI - Recovery in viscid line fibers. AB - The development of a reliable procedure for removing the viscous coating of viscid silk has allowed the accurate characterization of the tensile behavior of clean flagelliform silk (i.e., silk of the flagelliform gland without the viscous coating synthetised in the aggregate gland). For comparison, tensile tests on native viscid silk (with the viscous coating) fibers were also performed. It was found that viscid silk, either native or clean, has an elastomeric behavior when kept wet, either by immersion in water (clean fibers) or by the effect of the viscid coating (native fibers). When tested in dry environments (35% RH, relative humidity, for clean fibers and 10% RH for native fibers), their mechanical behavior was no longer elastomeric, with it being more similar to other silk fibers. Furthermore, it was noticed that flagelliform silk fibers show a ground state to which they can return independent of the previous loading history. PMID- 20355707 TI - Highly charged inorganic-organic colloidal core-shell particles. AB - Highly defined, hybrid inorganic-organic colloidal core-shell particles consisting of a silica core and a shell of fluorinated acrylate are prepared in a two-step route. The core-shell structure of the particles is investigated by means of small-angle X-ray scattering (SAXS). Because of highly acidic sulfonic acid surface groups resulting from the radical initiator sodium peroxodisulfate at the organic shell, long-range electrostatic interactions lead to the formation of liquidlike mesostructures. Increasing the effective interaction by reducing the next-neighbor distances induces a freezing of the liquidlike structures, i.e., a transition to crystalline and glassy structures. Because of the high electron density in the core and the fluorinated polymer shell, these particles are strong X-ray scatterers. In combination with the large number of effective charges and the outstanding monodispersity, these core-shell particles are a promising model system for the investigation of the glass transition by photon correlation spectroscopy employing coherent X-rays. PMID- 20355708 TI - Covalent attachment of polymersomes to surfaces. AB - We show that vesicles made of block copolymers with aldehyde end groups can be covalently attached to aminated and non-aminated, untreated glass surfaces. The attached vesicles were sufficiently stable to allow a detailed investigation of vesicle shapes by confocal laser scanning microscopy (CLSM) and AFM in aqueous solutions allowing reconstruction of 3D images of the vesicle structure. Covalently attached PCL-PEO, PLA-PEO, and PI-PEO block copolymer vesicles have different footprint areas and different shapes due to their differences in bilayer stiffness. PMID- 20355709 TI - Structural characterization of photopolymerizable binary liposomes containing diacetylenic and saturated phospholipids. AB - The use of liposomes to encapsulate materials has received widespread attention for drug delivery, transfection, diagnostic reagent, and as immunoadjuvants. Phospholipid polymers form a new class of biomaterials with many potential applications in medicine and research. Of interest are polymeric phospholipids containing a diacetylene moiety along their acyl chain since these kinds of lipids can be polymerized by Ultra-Violet (UV) irradiation to form chains of covalently linked lipids in the bilayer. In particular the diacetylenic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer. As knowledge of liposome structures is certainly fundamental for system design improvement for new and better applications, this work focuses on the structural properties of polymerized DC8,9PC:1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. Liposomes containing mixtures of DC8,9PC and DMPC, at different molar ratios, and exposed to different polymerization cycles, were studied through the analysis of the electron spin resonance (ESR) spectra of a spin label incorporated into the bilayer, and the calorimetric data obtained from differential scanning calorimetry (DSC) studies. Upon irradiation, if all lipids had been polymerized, no gel-fluid transition would be expected. However, even samples that went through 20 cycles of UV irradiation presented a DSC band, showing that around 80% of the DC8,9PC molecules were not polymerized. Both DSC and ESR indicated that the two different lipids scarcely mix at low temperatures, however few molecules of DMPC are present in DC8,9PC rich domains and vice versa. UV irradiation was found to affect the gel-fluid transition of both DMPC and DC8,9PC rich regions, indicating the presence of polymeric units of DC8,9PC in both areas. A model explaining lipids rearrangement is proposed for this partially polymerized system. PMID- 20355711 TI - Supramolecular assembly of Mg(II) complexes directed by associative lone pair pi/pi-pi/pi-anion-pi/pi-lone pair interactions. AB - Two Mg(II) malonate complexes with protonated 2-aminopyridine and protonated 2 amino-4-picoline as counterions, namely, (C(5)H(7)N(2))(4)[Mg(C(3)H(2)O(4))(2)(H(2)O)(2)](ClO(4))(2) (1) and (C(6)H(8)N(2)H)(2)[Mg(C(3)H(2)O(4))(2)(H(2)O)(2)] x 4 H(2)O (2) [C(5)H(7)N(2) = protonated 2-aminopyridine, C(3)H(4)O(4) = malonic acid, C(6)H(8)N(2)H = protonated 2-amino-4-picoline], have been synthesized from purely aqueous media, and their crystal structures have been determined by single-crystal X-ray diffraction. The role of lone pair...pi interactions in stabilizing the self assembly process appears to be of great importance in both complexes. Additional weak forces like anion...pi and noncovalent O...O interactions are also found to be operating in 1. A rare combination of lone pair...pi and anion...pi interactions in 1, of the type lone pair...pi/pi...pi/pi...anion...pi/pi...lone pair, is observed, and this unusual supramolecular network is fully described here. An attempt to prepare an analogous complex with 2-amino-4-picoline resulted in 2, which is isomorphous with our recently reported transition-metal complexes of the type (C(6)H(8)N(2)H)(2)[M(C(3)H(2)O(4))(2)(H(2)O)(2)] x 4 H(2)O (M = Ni/Co/Mn). A high-level DFT-D study (RI-B97-D/TZVP) has been used to characterize the different noncovalent interactions present in the solid state. We have also analyzed some crystal fragments to examine energetically some important assemblies that drive the crystal packing. Finally, we have studied the influence of magnesium on some hydrogen-bonding interactions. PMID- 20355712 TI - Novel 4-(piperidin-4-yl)-1-hydroxypyrazoles as gamma-aminobutyric acid(A) receptor ligands: synthesis, pharmacology, and structure-activity relationships. AB - A series of substituted 1-hydroxypyrazole analogues of the GABA(A) receptor partial agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL) have been synthesized and pharmacologically characterized. Several of the analogues displayed K(i) in the low nanomolar range at the native GABA(A) receptors and potent antagonism of the alpha(1)beta(2)gamma(2) receptor. It appears that several regions situated in proximity to the core of the orthosteric binding site of the GABA(A) receptor are able to accommodate large hydrophobic substituents. PMID- 20355710 TI - Structure of the ternary complex formed by a chemotaxis receptor signaling domain, the CheA histidine kinase, and the coupling protein CheW as determined by pulsed dipolar ESR spectroscopy. AB - The signaling apparatus that controls bacterial chemotaxis is composed of a core complex containing chemoreceptors, the histidine autokinase CheA, and the coupling protein CheW. Site-specific spin labeling and pulsed dipolar ESR spectroscopy (PDS) have been applied to investigate the structure of a soluble ternary complex formed by Thermotoga maritima CheA (TmCheA), CheW, and receptor signaling domains. Thirty-five symmetric spin-label sites (SLSs) were engineered into the five domains of the CheA dimer and CheW to provide distance restraints within the CheA:CheW complex in the absence and presence of a soluble receptor that inhibits kinase activity (Tm14). Additional PDS restraints among spin labeled CheA, CheW, and an engineered single-chain receptor labeled at six different sites allow docking of the receptor structure relative to the CheA:CheW complex. Disulfide cross-linking between selectively incorporated Cys residues finds two pairs of positions that provide further constraints within the ternary complex: one involving Tm14 and CheW and another involving Tm14 and CheA. The derived structure of the ternary complex indicates a primary site of interaction between CheW and Tm14 that agrees well with previous biochemical and genetic data for transmembrane chemoreceptors. The PDS distance distributions are most consistent with only one CheW directly engaging one dimeric Tm14. The CheA dimerization domain (P3) aligns roughly antiparallel to the receptor-conserved signaling tip but does not interact strongly with it. The angle of the receptor axis with respect to P3 and the CheW-binding P5 domains is bound by two limits differing by approximately 20 degrees . In one limit, Tm14 aligns roughly along P3 and may interact to some extent with the hinge region near the P3 hairpin loop. In the other limit, Tm14 tilts to interact with the P5 domain of the opposite subunit in an interface that mimics that observed with the P5 homologue CheW. The time domain ESR data can be simulated from the model only if orientational variability is introduced for the P5 and, especially, P3 domains. The Tm14 tip also binds beside one of the CheA kinase domains (P4); however, in both bound and unbound states, P4 samples a broad range of distributions that are only minimally affected by Tm14 binding. The CheA P1 domains that contain the substrate histidine are also broadly distributed in space under all conditions. In the context of the hexagonal lattice formed by trimeric transmembrane chemoreceptors, the PDS structure is best accommodated with the P3 domain in the center of a honeycomb edge. PMID- 20355714 TI - Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor. AB - Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5 c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3 one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442. PMID- 20355715 TI - Physical and chemical changes during the maturation of Gordal Sevillana olives ( Olea europaea L., cv. Gordal Sevillana). AB - A series of physical and chemical changes occur as olives mature on the tree, and these changes are important for the production of oil and table olives. The aim of this study was to increase the understanding of the maturation process of Gordal Sevillana olives, to optimize harvest timing, and to determine the most appropriate harvesting and post-harvesting processing methods. During maturation, the olive size, flesh/pit ratio, and oil content increased, with a maximum oil content of 72 g kg(-1) (wet weight). Changes in the fatty acid composition are reported. Levels of both total sugars and total phenolic compounds slightly decreased over the maturation period; however, we observed that these compounds were continually being synthesized until full black maturity. The optimal harvest time for the production of Gordal Sevillana as Spanish-style green olives occurred immediately prior to the color change from green to turning color, at which point the sugar levels and flesh/pit ratio were at maximum levels. PMID- 20355713 TI - Imaging progesterone receptor in breast tumors: synthesis and receptor binding affinity of fluoroalkyl-substituted analogues of tanaproget. AB - The progesterone receptor (PR) is estrogen regulated, and PR levels in breast tumors can be used to predict the success of endocrine therapies targeting the estrogen receptor (ER). Tanaproget is a nonsteroidal progestin agonist with very high PR binding affinity and excellent in vivo potency. When appropriately radiolabeled, it might be used to image PR-positive breast tumors noninvasively by positron emission tomography (PET). We describe the synthesis and PR binding affinities of a series of fluoroalkyl-substituted 6-aryl-1,4 dihydrobenzo[d][1,3]oxazine-2-thiones, analogues of Tanaproget. Some of these compounds have subnanomolar binding affinities, higher than that of either Tanaproget itself or the high affinity PR ligand R5020. Structure-binding affinity relationships can be rationalized by molecular modeling of ligand complexes with PR, and the enantioselectivity of binding has been predicted. These compounds are being further evaluated as potential diagnostic PET imaging agents for breast cancer, and enantiomerically pure materials of defined stereochemistry are being prepared. PMID- 20355716 TI - Detection and quantification of some plant growth regulators in a seaweed-based foliar spray employing a mass spectrometric technique sans chromatographic separation. AB - The sap expelled from the fresh harvest of Kappaphycus alvarezii , a red seaweed growing in tropical waters, has been reported to be a potent foliar spray. Tandem mass spectrometry of various organic extracts of the sap confirmed the presence of the plant growth regulators (PGRs) indole 3-acetic acid, gibberellin GA(3), kinetin, and zeatin. These PGRs were quantified in fresh state and after 1 year of storage by ESI-MS without recourse to chromatographic separation. Quantification was validated against HPLC data. The results may be useful in correlating with the efficacy of the sap. The methodology was extended to two other seaweeds. The method developed is convenient and precise and may find application in other agricultural formulations containing these growth hormones. PMID- 20355717 TI - Synthesis and bioassay of racemic and chiral trans-alpha-necrodyl isobutyrate, the sex pheromone of the grape mealybug Pseudococcus maritimus. AB - A concise synthesis of the racemic form of the female-produced pheromone of the grape mealybug was developed. The synthesis was readily adapted to production of both enantiomers of the pheromone via lipase-catalyzed kinetic resolution of an intermediate in the synthesis. Replicated field trials revealed that, contrary to a preliminary report, the (R,R)- rather than the (S,S)-enantiomer is the attractive stereoisomer. Lithium aluminum hydride reduction of the insect produced compound to alpha-necrodol followed by analysis on a chiral stationary phase GC column showed that the insect-produced material was actually an 85:15 mixture of the (R,R)- and (S,S)-enantiomers. The racemic form of the pheromone was highly attractive to male mealybugs, and in one of two field bioassays, the racemic material was significantly more attractive than the pure (R,R) enantiomer, suggesting that the (S,S)-enantiomer might act synergistically. PMID- 20355718 TI - Soluble polysaccharide composition and myo-inositol content help differentiate the antioxidative and hypolipidemic capacity of peeled apples. AB - Many people prefer to eat peeled apples. The present study investigated the composition of soluble polysaccharides (SP) in peeled apples and its antioxidative and hypolipidemic activity. The yield of SP ranged 0.43-0.88%, having MW ranging 223-848 kDa. All belonged to peptidoglycans. Among the fourteen amino acids found, seven were essential amino acids. In addition, sugar analysis indicated that 50% of apple samples consisted of glucoarabinan, 37.5% comprising taloarabinan and the remaining 12.5% containing alloglucan. Moreover, SP consisted of a huge amount of myo-inositol (>5.61%) and uronic acid (>11.7%), which may play a synergistic role in the hypolipidemic effect. Worth noting, we are the first who reported the presence of talose, allose and fucose in the apple SP. Conclusively, the biological value of SP is attributable to the differential effect of SP and the synergistic effect exerted by its unique SP pattern, high myo-inositol and uronic acid contents. PMID- 20355719 TI - Adsorption of a nonionic symmetric triblock copolymer on surfaces with different hydrophobicity. AB - This study investigates the adsorption of a symmetric triblock nonionic polymer comprising ethylene oxide (EO) and propylene oxide (PO) blocks (Pluronic P-105, EO(37)PO(56)EO(37)) on a range of substrates including hydrophobic, i.e., polypropylene (PP), poly(ethylene terephthalate) (PET), nylon, and graphite, and hydrophilic, i.e., cellulose and silica. The adsorption process and the structure of the hydrated adsorbed layers are followed by quartz crystal microgravimetry (QCM), surface plasmon resonance (SPR), and atomic force microscopy. The unhydrated surfaces are characterized by ellipsometry and contact angle techniques. The adsorption kinetics and the extent of adsorption are determined by monitoring the changes in resonance frequency and refractive index of sensors coated with ultrathin films of the various substrates. Langmuirian-type adsorption kinetics is observed in all cases studied. The amount of adsorbed Pluronic on hydrophobic polymer surfaces (PP, PET, and nylon) exceeds that on the hydrophilic cellulose. The hydrophobic (graphite) mineral surface adsorbs relatively low polymer mass, typical of a monolayer, while micellar structures are observed on the hydrophilic silica surface. The amount of water coupled to the adsorbed polymer layers is quantified by combining data from QCM, and SPR are found to increase with increasing polarity of the substrate. On the basis of contact angle data, the nonhydrated adsorbed structures produce modest increases in hydrophilicity of all the substrates investigated. Overall, insights are provided into the structure and stability of both hydrated and nonhydrated adsorbed triblock copolymer. PMID- 20355720 TI - Comprehensive LC-MS E lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients. AB - A fast and robust method for lipid profiling utilizing liquid chromatography coupled with mass spectrometry has been demonstrated and validated for the analysis of human plasma. This method allowed quantification and identification of lipids in human plasma using parallel alternating low energy and high energy collision spectral acquisition modes. A total of 275 [corrected] lipids were identified and quantified (as relative concentrations) in both positive and negative ion electrospray ionization mode. The method was validated with five nonendogenous lipids, and the linearity (r(2) better than 0.994) and the intraday and interday repeatability (relative standard deviation, 4-6% and 5-8%, respectively) were satisfactory. The developed lipid profiling method was successfully applied for the analysis of plasma from osteoarthritis (OA) patients. The multivariate statistical analysis by partial least-squares discrimination analysis suggested an altered lipid metabolism associated with osteoarthritis and the release of arachidonic acid from phospholipids. PMID- 20355721 TI - Authentication of Atlantic cod (Gadus morhua) using real time PCR. AB - This work describes the development of a real-time polymerase chain reaction (RT PCR) system for the detection and identification of Atlantic cod (Gadus morhua). Among the advantages of this technique, it is worth highlighting that this is reliable in terms of specificity and sensitivity. The TaqMan real-time PCR is the simplest, fastest testing process and has the highest potential for automation, therefore representing the currently most suitable method for screening, allowing the detection of fraudulent or unintentional mislabeling of this species. The method can be applied to all kinds of products, fresh, frozen, and processed products, including those undergoing intensive processes of transformation. The developed methodology using specific primer-probe set was validated and further applied to 40 commercial samples labeled as cod in order to determinate if the species used for their manufacturing corresponded to G. morhua, detecting 20% that were incorrectly labeled. A C(t) value of about 19 was obtained when G. morhua was present. In samples with a species mixture, all samples that had a fluorescence signal were positive (C(t) < 30) for the presence of G. morhua by conventional end-point RT-PCR, and the estimated limit of detection for these type of samples was of 20 pg of DNA. The methodology herein developed is useful to check the fulfilment of labeling regulations for seafood products and verify the correct traceability in commercial trade and for fisheries control. PMID- 20355722 TI - Langmuir-Blodgett films of pyridyldithio-modified multiwalled carbon nanotubes as a support to immobilize hydrogenase. AB - Pyridylthio-modified multiwalled carbon nanotubes (pythio-MWNTs) have been prepared by a reaction of the oxidized MWNTs with S-(2-aminoethylthio)-2 thiopyridine hydrochloride. The obtained pythio-MWNTs nanocomposites formed stable floating monolayers at the air-water interface, which were transferred onto substrate surfaces by the Langmuir-Blodgett (LB) method. Compositions and morphologies of the LB films were characterized by absorption, Raman, X-ray photoelectron spectra as well as by scan electron microscopy and atomic force microscopy. These pythio-MWNTs LB films were then used as a support to immobilize hydrogenase (H(2)ase) to form bionanocomposite of pythio-MWNTs-H(2)ase. Cyclic voltammograms for indium tin oxide electrode covered with the pythio-MWNTs H(2)ase films were investigated in both Ar and H(2) saturated 0.05 M KCl electrolyte solutions at pH from 4.0 to 9.0. A reversible redox couple of [4Fe 4S](2+/1+) clusters of H(2)ase was recorded when the pH value was 6.0 and 9.0, with reduction and oxidation potentials appearing at about -0.70 and -0.35 V vs Ag/AgCl, respectively. It was revealed that the H(2)ase was of high catalytic activity and strong stability in the LB films of pythio-MWNTs-H(2)ase. Hence, we suggested that the present bionanocomposites could be used as heterogeneous biocatalyst to catalyze reversible reaction between protons and H(2), resulting in potential applications in biohydrogen evolution and H(2) biofuel cells. PMID- 20355723 TI - Ion strength and pH sensitive phase transition of N-isobutyryl-L-(D)-cysteine monolayers on Au(111) surfaces. AB - Self-assembled monolayers (SAMs) of N-isobutyryl-L-(D)-cysteine (NIBC) on Au(111) surfaces were successfully prepared by immersing the Au(111) surfaces in the preheated pure NIBC aqueous solutions for a certain time and characterized by means of scanning tunneling microscopy. Close-packed lamellar structures with a rectangular (4 x radical3) lattice were found both in the SAMs of L-NIBC and D NIBC. The pH value of the aqueous solutions was found to be sensitive to adjust the SAM structures during the assembly. Changing the pH value from 5 to 7 may completely shift the SAM structures from close-packed lamellar phase to loose packed perpendicular phase. Combined with density functional theory calculations, such kind of phase transition was explained by the breaking of hydrogen bonds between carboxylic groups and the formation of extra interactions between COO(-) and Au. PMID- 20355724 TI - Direct detection of nitroxyl in aqueous solution using a tripodal copper(II) BODIPY complex. AB - The synthesis, photophysical properties, and a biological application of BODIPY triazole 1 (BOT1) are described. BOT1 juxtaposes a BODIPY fluorophore with a tripodal ligand platform via a triazole bridge. The triazole linker is afforded by azide-alkyne "click" chemistry and comprises the third arm of the tripodal architecture. BOT1 binds Cu(2+) in aqueous solution to form a Cu(II)[BOT1] complex in which emission from the BODIPY moiety is efficiently quenched. This complex exhibits a prompt turn-on response when exposed to nitroxyl, and this emission response is specific to HNO over other reactive nitrogen and oxygen species. Notably, Cu(II)[BOT1] does not fluoresce in the presence of nitric oxide, making this system the first discrete molecular probe capable of detecting HNO over NO under physiologically relevant conditions. Fluorescence microscopy experiments establish that Cu(II)[BOT1] is membrane-permeable and can successfully signal the presence of HNO in live cells. PMID- 20355725 TI - Fluorescent nano-optodes for glucose detection. AB - We have designed fluorescent nanosensors based on ion-selective optodes capable of detecting small molecules. By localizing the sensor components in a hydrophobic core, these nanosensors are able to monitor dynamic changes in concentration of the model analyte, glucose. The nanosensors demonstrated this response in vitro and also when injected subcutaneously into mice. The response of the nanosensors tracked changes in blood glucose levels in vivo that were comparable to measurements taken using a glucometer. The development of these nanosensors offers an alternative, minimally invasive tool for monitoring glucose levels in such fields as diabetes research. Furthermore, the extension of the ion selective optode sensor platform to small molecule detection will allow for enhanced monitoring of physiological processes. PMID- 20355726 TI - Effect of glycosylation on cis/trans isomerization of prolines in IgA1-hinge peptide. AB - The hinge region of human immunoglobulin A1 (IgA1), connecting the Fab and Fc regions, is mostly composed of Ser, Thr, and Pro (VPSTPPTPSPSTPPTPSPS); hinge peptide (HP). O-Glycans are naturally attached on only particular five Ser/Thr residues in this region. NMR was employed for analysis of the structural changes in HP upon the glycosylation, especially focusing on the cis/trans isomerization of Pro residues. A series of HP containing (13)C,(15)N-labeled Pro residues were chemically synthesized and enzymatically glycosylated. The signals from cis and trans forms of the labeled Pro were identified by two-dimensional NMR spectroscopy. Cis/trans ratios of the Pro residues at the C-terminal side of the glycosylated Ser/Thr were reduced from 9-10% to 2-3% by the glycosylation. Thermodynamic analyses indicated that the decrease in the cis/trans ratio was enthalpy-driven. Hydrogen-deuterium exchange experiments and NOE-based structure determination revealed that the intraresidue hydrogen bonds between the amide group of GalNAc and carbonyl oxygen of the peptide backbone of GalNAc-Thr are formed in the major trans conformers, which is consistent with the thermodynamic parameters. These hydrogen bonds largely restrict the psi angle of the peptide backbone and, thereby, should make the trans conformation of the C-terminal Pro residue more stable than the cis conformation. Namely, it is predicted that the restricted psi angle causes interresidue steric hindrance for the cis conformation. The appropriate glycosylation of HP probably contributes to the decrease in the unfavorable variety of relative orientations between Fab and Fc in IgA1, through stabilizing the conformation of HP. PMID- 20355727 TI - Prokaryotic ubiquitin-like protein (Pup) is coupled to substrates via the side chain of its C-terminal glutamate. AB - A prokaryotic protein tagging system called pupylation that is analogous to ubiquitylation in eukaryotes has recently been described. In this process, prokaryotic ubiquitin-like protein (Pup) is coupled to substrate proteins via an isopeptide bond in order to target them for degradation by the proteasome. The ligation occurs via a condensation reaction involving a carboxylate of the C terminal glutamate of Pup (located in a conserved terminal Gly-Gly-Glu motif) and the side-chain amino group of a substrate lysine. Here we have used a combination of NMR and biochemical experiments with free lysine and a physiological protein substrate (PanB) to show that the coupling occurs through the side-chain carboxylate of the glutamate in the GGE motif rather than the carboxy terminus but that the glutamate must be located at the C-terminal position to be coupled. PMID- 20355729 TI - Chiral boronate derivatives via catalytic enantioselective conjugate addition of Grignard reagents on 3-boronyl unsaturated esters and thioesters. AB - There is a growing interest in the development of new methods to prepare chiral organoboronate derivatives in optically pure form. An efficient copper-catalyzed enantioselective conjugate addition methodology using Grignard reagents and 3 boronyl acrylate derivatives was optimized for the preparation of chiral alkylboronate products in high yields and up to 98% ee. The resulting 1,8 diaminonaphthalene adducts can be transformed into the corresponding boronic acid, pinacol boronate, and trifluoroborate salt. This method extends the realm of chemical reactions compatible with useful boron-containing substrates. PMID- 20355728 TI - Uncovering the design rules for peptide synthesis of metal nanoparticles. AB - Peptides are multifunctional reagents (reducing and capping agents) that can be used for the synthesis of biocompatible metal nanoparticles under relatively mild conditions. However, the progress in peptide synthesis of metal nanoparticles has been slow due to the lack of peptide design rules. It is difficult to establish sequence-reactivity relationships from peptides isolated from biological sources (e.g., biomineralizing organisms) or selected by combinatorial display libraries because of their widely varying compositions and structures. The abundance of random and inactive amino acid sequences in the peptides also increases the difficulty in knowledge extraction. In this study, a "bottom-up" approach was used to formulate a set of rudimentary rules for the size- and shape-controlled peptide synthesis of gold nanoparticles from the properties of the 20 natural alpha-amino acids for AuCl(4)(-) reduction and binding to Au(0). It was discovered that the reduction capability of a peptide depends on the presence of certain reducing amino acid residues, whose activity may be regulated by neighboring residues with different Au(0) binding strengths. Another finding is the effect of peptide net charge on the nucleation and growth of the Au nanoparticles. On the basis of these understandings, several multifunctional peptides were designed to synthesize gold nanoparticles in different morphologies (nanospheres and nanoplates) and with sizes tunable by the strategic placement of selected amino acid residues in the peptide sequence. The methodology presented here and the findings are useful for establishing the scientific basis for the rational design of peptides for the synthesis of metal nanostructures. PMID- 20355731 TI - Highly diastereoselective preparation of homoallylic alcohols containing two contiguous quaternary stereocenters in acyclic systems from simple terminal alkynes. AB - The combined carbocupration of terminal alkynes followed by a zinc homologation and further reaction with ketones lead, in a single-pot operation, to the creation of homoallylic alcohols possessing two consecutive quaternary stereocenters with excellent diastereoselectivity. PMID- 20355730 TI - Measurement of the intramolecular isotope effect on aliphatic hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. AB - The non-heme iron enzyme phenylalanine hydroxylase from Chromobacterium violaceum has previously been shown to catalyze the hydroxylation of benzylic and aliphatic carbons in addition to the normal aromatic hydroxylation reaction. The intrinsic isotope effect for hydroxylation of 3-cyclochexylalanine by the enzyme was determined in order to gain insight into the reactivity of the iron center. With 3-[(2)H(11)-cyclohexyl]alanine as the substrate, the isotope effect on the k(cat) value was 1, consistent with an additional step in the overall reaction being significantly slower than hydroxylation. Consequently, the isotope effect was determined as an intramolecular effect by measuring the amount of deuterium lost in the hydroxylation of 3-[1,2,3,4,5,6-(2)H(6)-cyclohexyl]alanine. The ratio of 4 HO-cyclohexylalanine that retained deuterium to that which lost one deuterium atom was 2.8. This gave a calculated value of 12.6 for the ratio of the primary deuterium kinetic isotope effect to the secondary isotope effect. This value is consistent with hydrogen atom abstraction by an electrophilic Fe(O) center and a contribution of quantum-mechanical tunneling to the reaction. PMID- 20355732 TI - Quantum transport in graphene nanoribbons: effects of edge reconstruction and chemical reactivity. AB - We present first-principles transport calculations of graphene nanoribbons with chemically reconstructed edge profiles. Depending on the geometry of the defect and the degree of hydrogenation, spectacularly different transport mechanisms are obtained. In the case of monohydrogenated pentagon (heptagon) defects, an effective acceptor (donor) character results in strong electron-hole conductance asymmetry. In contrast, weak backscattering is obtained for defects that preserve the benzenoid structure of graphene. Based on a tight-binding model derived from ab initio calculations, evidence for large conductance scaling fluctuations are found in disordered ribbons with lengths up to the micrometer scale. PMID- 20355733 TI - Supercapacitors based on flexible graphene/polyaniline nanofiber composite films. AB - Composite films of chemically converted graphene (CCG) and polyaniline nanofibers (PANI-NFs) were prepared by vacuum filtration the mixed dispersions of both components. The composite film has a layered structure, and PANI-NFs are sandwiched between CCG layers. Furthermore, it is mechanically stable and has a high flexibility; thus, it can be bent into large angles or be shaped into various desired structures. The conductivity of the composite film containing 44% CCG (5.5 x 10(2) S m(-1)) is about 10 times that of a PANI-NF film. Supercapacitor devices based on this conductive flexible composite film showed large electrochemical capacitance (210 F g(-1)) at a discharge rate of 0.3 A g( 1). They also exhibited greatly improved electrochemical stability and rate performances. PMID- 20355734 TI - Bronsted acid-catalyzed cascade cycloisomerization of enynes via acetylene cations and sp3-hybridized C-H bond activation. AB - A novel Bronsted acid-catalyzed cascade cycloisomerization of cyclic and acyclic enynes via acetylene cation cyclization followed by cleavage of the entirely inactive C(sp(3))-H bond is described. The reaction proceeds efficiently under mild conditions to afford various tri- and bicyclic compounds in good to high yields. PMID- 20355735 TI - Borinium cations as sigma-B-H ligands in osmium complexes. AB - The complex OsH(2)Cl(2)(P(i)Pr(3))(2) reacts with pinacolborane, Me(2)NH-BH(3), and (t)BuNH(2)-BH(3) to give the complexes OsH(2)Cl{eta(2) HBOC(CH(3))(2)C(CH(3))(2)OBpin}(P(i)Pr(3))(2) and OsH(2)Cl(eta(2) HBNR(1)R(2))(P(i)Pr(3))(2) (R(1) = R(2) = Me; R(1) = H, R(2) = (t)Bu) containing monosubstituted alkoxy- and amidoborinium cations coordinated as sigma-B-H ligands. The process is proposed to take place via the electrophilic 14-valence electron fragment OsHCl(P(i)Pr(3))(2), which promotes hydride transfer from the corresponding borane to the osmium atom. PMID- 20355736 TI - Flexible germanium nanowires: ideal strength, room temperature plasticity, and bendable semiconductor fabric. AB - The mechanical strengths of individual germanium (Ge) nanowires with 111 growth direction and diameters ranging from 23 to 97 nm were measured by bending each with a robotic nanomanipulator in a scanning electron microscope (SEM). The nanowires tolerate diameter-dependent flexural strains of up to 17% prior to fracture, which is more than 2 orders of magnitude higher than bulk Ge. The corresponding bending strength of 18 GPa is in agreement with the ideal strength of 14-20 GPa for a perfect Ge crystal. Nanowires also exhibited plastic deformation at room temperature, becoming amorphous at the point of maximum strain. A bendable, nonwoven fabric, or paper, of Ge nanowires is demonstrated. PMID- 20355737 TI - Photoluminescence and spectroelectrochemistry of single ag nanowires. AB - We present strong photoluminescence from single Ag nanowires (NWs), their disordered blinking behavior, and their dependence on substrate potential. The stochastic bursts (<10 ms) in the photoluminescence trajectories of single Ag NWs in air are observed and attributed to the photoactivated fluorescence silver clusters. The dynamic changes in the photoluminescence are analyzed using autocorrelation function, statistical analysis of the stochastic durations, and probability density function to reveal the disordered nature of the spontaneous photochemical reaction at each individual Ag NWs under laser irradiation. Stable PL is observed for single Ag NWs in alkaline electrolyte and is found to be highly dependent on the electrochemical potential. The PL from single Ag NWs is found to be weakly dependent on polarization direction of the incident light and strongly dependent on the interactions with adjacent NWs. PMID- 20355738 TI - Breaking the T1 constraint for quantitative measurement in magic angle spinning solid-state NMR spectroscopy. AB - Quantitative solid-state NMR experimental schemes that break the conventional T(1) constraint are described. The combination of broad-band homonuclear recoupling techniques and the conventional single pulse or cross-polarization (CP) schemes (referred as QUSP or QUCP) render the long T(1) of low-gamma spins no longer a constraint for obtaining quantitative NMR spectra. During the mixing time when dipolar recoupling occurs, the nonuniformly CP enhanced or recovered spin magnetization is redistributed under the reintroduced homonuclear dipole dipole interactions so that uniformly enhanced or recovered magnetization is achieved when the system reaches the quasi-equilibrium state. It is shown that quantitative NMR spectra can be obtained for the recycle delays substantially shorter than the conventionally required 5T(1). In addition, the high efficiency gain can be achieved in QUSP and QUCP experiments with a relatively short recycle delay. PMID- 20355739 TI - Iron oxide nanosized clusters embedded in porous nanorods: a new colloidal design to enhance capabilities of MRI contrast agents. AB - Development of nanosized materials to enhance the image contrast between the normal and diseased tissue and/or to indicate the status of organ functions or blood flow is essential in nuclear magnetic resonance imaging (MRI). Here we describe a contrast agent based on a new iron oxide design (superparamagnetic iron oxide clusters embedded in antiferromagnetic iron oxide porous nanorods). We show as a proof-of-concept that aqueous colloidal suspensions containing these particles show enhanced-proton relaxivities (i.e., enhanced MRI contrast capabilities). A remarkable feature of this new design is that large scale production is possible since aqueous-based routes are used, and porosity and iron oxide superparamagnetic clusters are directly developed from a single phase. We have also proved with the help of a simple model that the physical basis behind the increase in relaxivities lies on both the increase of dipolar field (interactions within iron oxide clusters) and the decrease of proton-cluster distance (porosity favors the close contact between protons and clusters). Finally, a list of possible steps to follow to enhance capabilities of this contrast agent is also included (partial coating with noble metals to add extra sensing capacity and chemical functionality, to increase the amount of doping while simultaneously carrying out cytotoxicity studies, or to find conditions to further decrease the size of the nanorods and to enhance their stability). PMID- 20355740 TI - Acidic pH-responsive nanogels as smart cargo systems for the simultaneous loading and release of short oligonucleotides and magnetic nanoparticles. AB - Smart materials able to sense environmental stimuli can be exploited as intelligent carrier systems. Acidic pH-responsive polymers, for instance, exhibit a variation in the ionization state upon lowering the pH, which leads to their swelling. The different permeability of these polymers as a function of the pH could be exploited for the incorporation and subsequent release of previously trapped payload molecules/nanoparticles. We provide here a proof of concept of a novel use of pH-responsive polymer nanostructures based on 2-vinylpyridine and divinylbenzene, having an overall size below 200 nm, as cargo system for magnetic nanoparticles, for oligonucleotide sequences, as well as for their simultaneous loading and controlled release mediated by the pH. PMID- 20355741 TI - Synthesis and physicochemical characterization of new twin-tailed N-oxide based gemini surfactants. AB - New gemini surfactants (GSs) constituted by two double alkyl chain (from 7 to 17 methylenic units) N-oxide monovalent surfactants joined by a PEG spacer of different length (from 3 to 21 ethylene glycol units), thus combining the properties of both N-oxide and GS surfactants, were synthetized and characterized. The different hydrophilic/hydrophobic balance of the molecular structure strongly influences the morphology and the electrical features of the aggregates. Despite the zwitterionic nature of the polar head groups, all the aggregates are characterized by positive potential thus suggesting protonation at the interface; however, the extent of protonation was shown to strongly depend on the length of the alkyl chain and of the spacer. PMID- 20355742 TI - Preparation of syn-tertiary homoallylic alcohols utilizing allenyltitanocenes generated by reductive titanation of gamma-trimethylsilylpropargylic carbonates. AB - syn-Tertiary homoallylic alcohols were obtained by the reaction of alpha silylallenyltitanocenes generated by the reductive titanation of gamma silylpropargylic carbonates with Cp(2)Ti[P(OEt)(3)](2) with ketones and following desilylation and partial hydrogenation. High diastereoselectivity was observed when aromatic and alpha,beta-unsaturated ketones were employed. PMID- 20355743 TI - Total synthesis of (+)-decarbamoylsaxitoxin and (+)-gonyautoxin 3. AB - Facile construction of the complex saxitoxin (STX) skeleton is carried out by using a novel, conformationally controlled, guanidine cyclization process that relies on the use of neighboring group participation. The utility of this methodology is verified by its employment in syntheses of both natural and unnatural STX derivatives. PMID- 20355744 TI - Application of poly(amidoamine) dendrimers for use in bionanomotor systems. AB - The study and utilization of bionanomotors represents a rapid and progressing field of nanobiotechnology. Here, we demonstrate that poly(amidoamine) (PAMAM) dendrimers are capable of supporting heavy meromyosin dependent actin motility of similar quality to that observed using nitrocellulose, and that microcontact printing of PAMAM dendrimers can be exploited to produce tracks of active myosin motors leading to the restricted motion of actin filaments across a patterned surface. These data suggest that the use of dendrimer surfaces will increase the applicability of using protein biomolecular motors for nanotechnological applications. PMID- 20355745 TI - Editorial: Launch of ACS Applied Materials & Interfaces. PMID- 20355746 TI - Selective electroless metallization of patterned polymeric films for lithography applications. AB - The fabrication of electrical interconnects to provide power for and communication with computers as their component complementary metal oxide semiconductor (CMOS) devices continue to shrink in size presents significant materials and processing compatibility challenges. We describe here our efforts to address these challenges using top-surface imaging and hybrid photoresist/self assembled monolayer patterning approaches, in conjunction with selective electroless metal deposition, to develop processes capable of fabricating appropriate submicron and nanoscale metal features useful as electrical interconnects, as well as plasma-etch-resistant masks and metal diffusion barriers. Our efforts focus on the development of cost-effective methods compatible with a manufacturing environment that satisfy materials and process constraints associated with CMOS device production. We demonstrate the fabrication of approximately 50-nm-width features in metal with high fidelity and sufficient control of edge acuity to satisfy current industry design rules using our processes and discuss the challenges and opportunities for fabrication of analogous sub-10-nm metal features. PMID- 20355747 TI - Self-assembled chitosan nanotemplates for biomineralization of controlled calcite nanoarchitectures. AB - Three-dimensional chitosan self-assembled nanostructures are reported whose morphology can be adjusted by tuning of the processing parameters, including the rate of solvent removal, the surface roughness of the substrate, and the polarity of the solvent used. Upon this, chitosan nanostructures of more interesting morphology and even higher complexity can be prepared, which can serve as nanotemplates for subsequent biomineralization of calcium carbonate, leading to controllable three-dimensional biominerals having the same complex morphology as that exhibited by the self-assembled chitosan nanotemplates. PMID- 20355748 TI - Cell adhesion and spreading behavior on vertically aligned silicon nanowire arrays. AB - In this report, we studied the interactions between biological cells and vertically aligned silicon nanowire (SiNW) arrays and focused on how SiNW arrays affected cellular behaviors such as cell adhesion and spreading. We observed that SiNW arrays could support cell adhesion and growth and guide cell adhesion and spreading behaviors. The results also showed that SiNW arrays could not only enhance the cell-substrate adhesion force but also restrict cell spreading. Combining the results from scanning electron microscopy images of cell morphology and the expression analysis of genes and proteins related to cell adhesion and spreading process, we proposed a mechanism on how cell adhesion and spreading was controlled by arrayed SiNWs. The effects of SiNW arrays in guiding cell adhesion and spreading behavior might be useful in the development of cell microarrays, tissue engineering scaffolds, and molecule delivery vehicles in which strong cell substrate adhesion and reduced cell-cell communication were beneficial. PMID- 20355749 TI - Novel calcium carboxyphosphonate/polycarboxylate inorganic-organic hybrid materials from demineralization of calcitic biomineral surfaces. AB - Dissolution of biologically important sparingly soluble salts, such as calcium carbonate and calcium oxalate, is possible by use of carboxyl- and carboxyl/phosphonate-bearing, anionic additives, citrate, malate, carboxyphosphonate, and butane tetracarboxylate. Calcium-containing dissolution products have been identified, characterized, and independently synthesized. These are polymeric materials composed of calcium and the additive as the ligand. Their full characterization was carried out by single-crystal X-ray crystallography and other techniques. PMID- 20355751 TI - Instabilities and pattern transformation in periodic, porous elastoplastic solid coatings. AB - Pattern transformation in periodic microporous elastoplastic solid coatings is caused by a buckling of the struts and a rotation of the nodes under compressive stresses. The results of a nonlinear numerical investigation confirm the critical role of the bifurcation of the periodic solid under compressive stresses. In striking contrast to the earlier observations of elastic instabilities in porous elastomeric solids, the elastic-plastic nature of the cross-linked periodic microstructure studied here provides the ability to lock in the transformed pattern with complete relaxation of the internal stresses. The study unveils a novel deformation mode in porous periodic solids in the form of organized buckling instability of weak strut elements. PMID- 20355750 TI - Surface self-concentrating amphiphilic quaternary ammonium biocides as coating additives. AB - A variety of amphiphilic quaternary dimethylammonium compounds bearing n-alkyl and oxyethylene groups have been designed and synthesized as antimicrobial additives for use in self-decontaminating surfaces. The effectiveness of these additives stems from a unique ability to self-concentrate at the air-polymer interface without the incorporation of exotic perfluorinated or polymeric functionalities. X-ray photoelectron spectroscopy analysis reveals surface enrichment as high as 18-fold, providing a 7-log reduction of both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The migration to the surface is a consequence of the hydrophobicity of the additive within the hydrophilic polyurethane resin, over which an unprecedented level of control can be exerted by altering the lengths of the n-alkyl and oxyethylene groups. Thus, for the first time, specific surface and bulk coating concentrations can be achieved as desired using a single class of antimicrobial additives. PMID- 20355752 TI - Conjugated polyelectrolyte capsules: light-activated antimicrobial micro "Roach Motels". AB - Microcapsules consisting of alternating layers of oppositely charged poly(phenylene ethynylene)-type conjugated polyelectrolytes (CPEs) were prepared via layer-by-layer deposition onto MnCO3 template particles followed by dissolution of the template particles using an ethylenediaminetetraacetate solution. The resulting microcapsules exhibit bright-green fluorescence emission characteristics of the CPEs. Strong antimicrobial activity was observed upon mixing of polyelectrolyte capsules with Cobetia marina or Pseudomonas aeruginosa followed by white-light irradiation. It was demonstrated that the materials act as highly effective light-activated micro "Roach Motels" with greater than 95% kill after exposure to approximately 1 h of white light. PMID- 20355753 TI - Surface-displayed antibodies as a tool for simultaneously controlling the arrangement and morphology of multiple cell types with microscale precision. AB - Cell-cell interactions are considered to play critical roles in the development and physiology of most tissues. However, it is not straightforward to analyze cell-cell interactions with conventional cell culture in which cells are randomly distributed. To overcome this limitation, we employed here an antibody display to sort different cell types onto separate regions on a single substrate with microscale precision, taking advantage of the specific recognition of cell surface markers by surface-displayed antibodies. The results obtained with two sets of cell combinations, T cell/myelomonocytoid cell and neuron/astrocyte, demonstrate that antibody displays are feasible to establish a site-addressable coculture. PMID- 20355754 TI - SERS study of the controllable release of nitric oxide from aromatic nitrosothiols on bimetallic, bifunctional nanoparticles supported on carbon nanotubes. AB - A hybrid system comprising bimetallic nanoparticles supported on carbon nanotubes (CNTs) was engineered to maximize the surface-enhanced Raman scattering signal from solution by generating a high density of hot spots with reproducible enhancing activity and long-term colloidal and optical stability. CNT@AgAu was employed as a bifunctional material to catalyze and monitor the controlled release of nitric oxide from aromatic nitrosothiols, as a function of the gold content. PMID- 20355755 TI - Conductivity switching and electronic memory effect in polymers with pendant azobenzene chromophores. AB - Electronic memory devices having the indium-tin oxide/polymer/Al sandwich structure were fabricated from polymers containing pendant azobenzene chromophores in donor-acceptor structures. The reversibility, or rewritability, of the high-conductivity (ON) state was found to be dependent on the terminal moiety of the azobenzene chromophore. While the polymers with electron-accepting terminal moieties (-Br or -NO2) in the pendant azobenzene exhibit write-once, read-many-times (WORM) type memory behavior, those with electron-donating terminal moieties (-OCH3) exhibit rewritable (FLASH) memory behavior. The WORM memory devices have low switching ("write") voltages below -2 V and high ON/OFF current ratios of about 10(4)-10(6). The polarity of the "write" voltage can be reversed by using an electrode with a higher work function than Al, thus excluding metallic filamentary conduction as a cause of the bistable switching phenomenon. The FLASH memory devices have low "write" and "erase" voltages of about -1.7 to -1.8 V and 2.0 to 2.2 V, respectively, and ON/OFF current ratios of about 10(3)-10(4). The electrical bistability observed can be attributed to charge trapping at the azobenzene chromophores, resulting in the charge separated, high-conductivity state. The proposed mechanism is supported experimentally by a red shift and peak broadening in the UV-visible absorption spectra of the polymer films resulting from the OFF-to-ON electrical transition. PMID- 20355756 TI - A facile route to create surface porous polymer films via phase separation for antireflection applications. AB - A facile route was developed to create surface porous polystyrene/poly(vinylpyrrolidone) (PS/PVP) films, via phase separation in a dip coating process, for antireflection applications. The film thickness, pore size, and pore depth of the product films can be effectively adjusted with the concentration of the PS/PVP (volume ratio of 7:3) solution and withdrawal speed. At an optimal concentration of 0.6 wt % and withdrawal speed of 19 cm/min, the product films had an average thickness of 125 nm, a pore size of 156 nm, and a pore depth of 20 nm, giving a percent transmittance increase of 3-4% over the bare glass. Further removal of the PVP phase, which was concentrated at the pore bottom, with water etching deepened the pore depth to 37 nm, thus boosting the percent transmittance for another 0.5%. PMID- 20355757 TI - Red-emission oligofluorene electrophosphorescent diodes based on bis[2-(9,9 dihexyl-9H-fluoren-2-yl)quinolineC3,N]acetylacetonatoiridium(III) and solvent treatment for interface modification. AB - Efficient solution-processed organic light emitting diodes based on oligofluorene doped with bis[2-(9,9-dihexyl-9H-fluoren-2-yl)quinoline-C3,N]- acetylacetonatoiridium(III) [Ir(C6flq)2(acac)] have been demonstrated. The oligofluorene and [Ir(C6flq)2(acac)] show excellent solubility and processibility, with a device performance of 7.83+/-0.52 cd A(-1) and 3.30+/-0.10 lm W(1-) at 2479+/-45 cd m(-2) brightness with Commission International de L'Eclairage coordinates (0.66, 0.33). It was discovered that the efficiency can be further enhanced by exposing the finished organic thin film to a polar solvent or solvent vapor before deposition of the cathode contact. As a result, a peak efficiency of 12.20+/-0.16 cd A(-1) and 6.35+/-0.03 lm W(1-) at 1821+/-238 cd m( 2) brightness is achieved. This efficiency enhancement can be attributed to the presence of interface dipoles between the light-emitting layer and cathode contact. PMID- 20355758 TI - High-contrast solid-state electrochromic devices of viologen-bridged polysilsesquioxane nanoparticles fabricated by layer-by-layer assembly. AB - Water-soluble silsesquioxane nanoparticles (NPs) incorporating viologen groups (PXV; 1,1'-bis[3-(trimethoxysilyl)propyl]-4,4'-bipyridinium iodide) have been synthesized by sol-gel polymerization. The electrochromic properties of the bulk film fabricated by layer-by-layer (LbL) assembly have been examined, along with their incorporation into solid-state devices. The orange LbL films show high thermal stability and exhibit a maximum UV-vis absorption at 550 nm. Electrochromic switching of the NPs in liquid electrolyte as well as in the solid state was evaluated by a kinetic study via measurement of the change in transmission (% T) at the maximum contrast. Cyclic voltammograms of the PXV NP LbL films exhibit a reversible reduction at -0.6 V vs Ag/AgCl in a 0.1 M NaClO4(aq) solution, revealing good electrochromic stability, with a color change from orange to dark purple-blue at applied potentials ranging from -0.7 to -1.3 V. Cathodically coloring PXV NP solid-state devices exhibit a switching time of a few seconds between the purple-blue reduced state and the orange oxidized state, showing a contrast of 50% at 550 nm and a coloration efficiency of 205 cm2/C. Their solubility and fairly fast electrochromic switching ( approximately 3 s) at low switching voltages (between 0 and 3.0 V), along with their stability under atmospheric conditions, make PXV NPs good candidates for electrochromic displays. PMID- 20355759 TI - Synthesis and characterization of solution-processable polyelectrolyte complexes and their homogeneous membranes. AB - Solution-processable polyelectrolyte complexes (PECs) between poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were synthesized in aqueous NaOH and obtained in their solid forms by protection and deprotection of carboxylic acid groups. Elemental analysis, conductance measurement, and FT-IR showed that the composition and ionic complexation degree (ICD) of the PECs can be controlled effectively by tuning the NaOH concentration in both parent polyelectrolyte solutions. Thermal gravity analysis showed that PECs revealed good thermal stability, and differential scanning calorimetry showed that the glass transition temperature (Tg) of PECs increased with increasing ICD and finally became undetectable when ICD was above 0.16. Viscosity properties of the PEC solutions were well correlated to the ICD of PECs, and it was found that solid PECs could be redissolved in dilute NaOH without breaking the ionic complexation between PDDA and PAA. Homogeneous PEC membranes (HPECMs) were made from their concentrated solutions, and their morphologies were examined by field emission scanning electron microscopy. These novel HPECMs were subjected to dehydration of organics for the first time, and a very promising performance was obtained. Furthermore, another two solution-processable PECs between weak anionic polyelectrolyte and cationic polyelectrolyte were also synthesized by the same method and showed a very high separation performance. PMID- 20355760 TI - Maximum conductivity of packed nanoparticles and their polymer composites. AB - Adding conductive fillers to nonconductive polymers is a common way to make soft conductive materials such as conductive adhesives. An important issue is how to achieve high volume conductivity with acceptable mechanical performance. Two questions pertaining to this issue were studied in this paper. One question was whether the maximum conductivity benefits from larger or smaller particle sizes. The second was what is the maximum achievable conductivity. One incentive for this work is the recent availability of nanomaterials that provide opportunities to make conductive composites using much smaller particles than in the past. We found that the conductivity of platinum, carbon black, and silver particles in their polyurethane composites did not vary greatly with particle size (from micrometer to nanometer range). What was unexpected was that in all the composite examples, the highest conductivity achieved was only on the order of 1% of that of the pure bulk conductive materials. Further experiments to emulate these conductive composites with platinum, carbon black, copper, and nickel particles without polymer matrix showed similar results, indicating the issue is not simply dispersion homogeneity, nano versus macro particles, particle connectivity/percolation, or the presence of the matrix materials. We interpret this to mean that the composite systems are intrinsically limited by the contact between filler particles. PMID- 20355761 TI - Water-induced degradation of polymer solar cells studied by H2(18)O labeling. AB - Water-induced degradation of polymer photovoltaics based on the active materials poly(3-hexylthiophene) (P3HT) or poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4 phenylenevinylene] (MEHPPV) was studied. The solar cell devices comprised a bulk heterojunction formed by the active material and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) in a standard device geometry. The use of H2(18)O in conjunction with time-of-flight secondary ion mass spectrometry enabled mapping of the parts of the device that were induced by water. A comparison was made between the two active materials and between devices that were kept in the dark and devices that had been subjected to illumination under simulated sunlight. Devices that were exposed to ambient humidity were compared to devices exposed to saturated humidity. Finally, a comparison was made between results obtained using H2(18)O and earlier work involving 18O2. Water was found to have behavior similar to but not identical with molecular oxygen. PMID- 20355762 TI - Novel thrombo-resistant coating based on iron-polysaccharide complex multilayers. AB - The biocompatibility of iron-polysaccharide complexes has been well-documented. Herein, a stable thrombo-resistant coating was fabricated by consecutive adsorption of Fe (III) and polysaccharides including heparin (Hep) and dextran sulfate (DS) onto various surface by layer-by-layer self-assembly technique via both electrostatic interaction and chemical complexation process. The absorbance at 350 nm increased linearly with the number of Fe3+/Hep multilayer, indicating the formation of multilayer structure and the uniform coating. Compared with (Fe3+/Hep)10, the (Fe3+/DS/Fe3+/Hep)5 coating was more hydrophilic and stable due to the incorporation of DS. The activated partial thromboplastin time (APTT) and platelet adhesion assays showed that both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coated surfaces were anticoagulant. The complexing with ferric ions did not compromise the catalytic capacity of heparin to promote antithrombin(III) mediated thrombin inactivation. Chromogenic assays for heparin activity proved definitively that the inhibition of locally produced thrombin was contributed to the thromboresistance of the surface-bound heparin. The surface with Hep or DS as the outmost layer showed stronger anticoagulant activity than Fe3+, indicating that the outermost layer of the coating played a key role in anticoagulant activity. The utilization of dextran sulfate/heparin surfaces was more advantageous than merely the heparin surface for improving blood-contacting medical devices for long-term usage. PMID- 20355763 TI - Multiplex lateral-flow test strips fabricated by two-dimensional shaping. AB - We have fabricated paper- and nitrocellulose-based lateral-flow devices that are shaped in two dimensions by a computer-controlled knife. The resulting star, candelabra, and other structures are spotted with multiple bioassay reagents to produce multiplex lateral-flow assays. We have also fabricated laminar composites in which porous nitrocellulose media are sandwiched between vinyl and polyester plastic films. This minimizes evaporation, protects assay surfaces from contamination and dehydration, and eliminates the need for the conventional hard plastic cassette holders that are typically used to package commercial lateral flow diagnostic strips. The reported fabrication method is novel, low-cost, and well-suited to (i) fabrication and adoption in resource-poor areas, (ii) prototype development, (iii) high-volume manufacturing, and (iii) improving rates of operator error. PMID- 20355764 TI - A simple method to improve the clarity and rheological properties of polymer/clay nanocomposites by using fractionated clay particles. AB - We present a simple method to improve the transparency and rheological properties of polystyrene/organoclay nanocomposites. Such composites are typically prepared using organophilic derivatives of commercial montmorillonite (MMT) clays that contain a wide range of particle sizes. Our approach is to fractionate the native MMT clay to exclude large aggregates and then modify the fractionated clay (FMT) by a surfactant treatment (the resulting organoclay is termed o-FMT). Polystyrene nanocomposites made from the o-FMT are then compared with those made from a commercial organoclay having the same surfactant treatment. The o-FMT-based composites exhibit much better rheological properties (e.g., their elastic moduli at low frequencies are approximately 10 times higher) at equivalent mass loadings. Moreover, the o-FMT-based materials also have better transparency: e.g., a 10% o-FMT sample transmits as much light as a sample with 5% commercial clay. Transmission electron microscopy confirms that these differences in properties are related to microstructural differences; i.e., large aggregates are generally absent in the o-FMT samples. Clay fractionation may thus be a general strategy to enhance the properties of polymer/clay nanocomposites. PMID- 20355765 TI - Submicron trenches reduce the Pseudomonas fluorescens colonization rate on solid surfaces. AB - Bacterial adhesion and spreading on biomaterials are considered key features of pathogenicity. Roughness and topography of the substrate have been reported to affect bacterial adhesion, but little is known about their effect on spreading. Submicron row and channel tuning with bacterial diameter (S2) were designed to test bacterial motility on these surfaces. Random nanometer-sized structures (S1) were used as controls. Optical microscopy and AFM were employed to detect biological and surface pattern details in the micro- and nanoscale, respectively. Results showed that motility strategies (flagella orientation, elongation, aggregation in rafts, formation of network structures, and development of a bacterial frontier) were affected by the presence of submicropatterns. Importantly, the rate of bacterial spreading on S2 was significantly reduced and influenced by the orientation of the submicropatterns. Consequently, submicroengineered substrates could be employed as a tool to downgrade bacterial colonization. Such patterns could impact on the design of proper engineered structures to control biofilm spreading on solid surfaces. PMID- 20355766 TI - Bioelectrocatalytic system coupled with enzyme-based biocomputing ensembles performing boolean logic operations: approaching "smart" physiologically controlled biointerfaces. AB - The modified electrode for electrocatalytic oxidation of NADH was developed using a pH-switchable redox interface. The operation of the modified electrode was controlled by logic operations performed by enzyme systems processing biochemical input signals. The electrocatalytic oxidation of NADH was activated upon appropriate combinations of the signals processed by the AND/OR logic operations performed by the enzymes. The modified interface was reset in a mute nonactive state by another enzyme reaction. The coupling between the enzyme logic systems and the bioelectrocatalytic interface was achieved by pH changes produced in situ by the enzyme reactions, resulting in different protonation states of the polymeric matrix associated with the electrode surface. The bioelectrocatalytic system integrated with biochemical computing systems opens the way to novel "smart" interfaces for multisignal biosensors and signal-controlled biofuel cells. In a long perspective, this approach will allow physiological control of implantable bioelectronic devices. PMID- 20355767 TI - Low-band-gap platinum acetylide polymers as active materials for organic solar cells. AB - We report on two pairs of platinum acetylide based polymers and model oligomers utilizing a 2,1,3-benzothiadiazole (BTD) acceptor moiety flanked on either side by either 2,5-thienyl donor units (Pt2BTD-Th and p-PtBTD-Th) or (3,4 ethylenedioxy)-2,5-thienyl donors (Pt2BTD-EDOT and p-PtBTD-EDOT). Both oligomer/polymer pairs absorb strongly throughout the visible region; however, because the (ethylenedioxy)thiophene moiety is a stronger donor than thiophene, the latter oligomer/polymer pair has a correspondingly lower band gap and, therefore, harvests light more efficiently at longer wavelengths. p-PtBTD-Th exhibits a relatively narrow molecular weight distribution with a number-average molecular weight (Mn) of 22 kDa, while p-PtBTD-EDOT exhibits a comparable Mn of 33 kDa but has a high polydispersity index likely due to aggregation. We provide a complete report of the photophysical and electrochemical characterization of the two oligomer/polymer pairs. The photophysical studies reveal that the materials undergo relatively efficient intersystem crossing. In a discussion of the energetics of photoinduced electron transfer from the platinum polymers to [6,6]-phenyl C61 butyric acid methyl ester (PCBM), it is noted that while the singlet state is quenched efficiently, the triplet state is not quenched, indicating that charge generation in the photovoltaic materials must ensue from the singlet manifold. Finally, organic photovoltaic devices based on blends of p PtBDT-Th or p-PtBDT-EDOT with PCBM were characterized under monochromatic and simulated solar (AM1.5) illumination. Optimized devices exhibit an open-circuit voltage (Voc) of approximately 0.5 V, a short-circuit current density (Isc) of approximately 7.2 mA cm(-2), and a fill factor of approximately 35%, which yields overall power conversion efficiencies of 1.1-1.4%. PMID- 20355768 TI - New high-throughput screening protease assay based upon supramolecular self assembly. AB - We previously demonstrated that the supramolecular self-assembly of cyanines could be useful for developing fluorescent enzymatic assays. We took that concept a step further by synthesizing a covalent adduct of the tetrapeptide Asp-Glu-Val Asp (DEVD) and a cyanine (DEVD-cyanine). The DEVD-cyanine due to its canonical sequence was recognized and hydrolyzed by the proteases, Caspase-3 and -7 in 96- or 384-microwell plate reactions. The catalytically liberated cyanine self assembled upon scaffolds of carboxymethylamylose (CMA), carboxymethylcellulose (CMC), or a mixture of CMA and CMC resulting in a J aggregate exhibiting bright fluorescence at a 470 nm emission wavelength (optimum signal/background using excitation wavelengths of 415-440 nm). The fluorescence intensity increased with enzyme and substrate concentrations or reaction time and exhibited classical saturation profiles of a rectangular hyperbola. Saturation of the reaction was at 30 U/mL (1 microg/mL) Caspase-3 and 250 microM DEVD-cyanine. The reaction kinetics was linear between 1 and 20 min and saturated at 60 min. The affinity constant (Km) for DEVD-cyanine was approximately 23 microM, similar to those of previously reported values for other DEVD substrates of Caspase-3. Maximal fluorescence emission was observed by using a mixture of CMA and CMC scaffolds at 65 and 35 microM, respectively. The reaction kinetics of Caspase-7 executed in a 384-well plate was similar to the reaction kinetics of Caspase-3 conducted in a 96-well plate. We believe that this is the first demonstration of a cyanine liberated from a covalent adduct due to protease action, leading to supramolecular self-assembly and the detection of protease activity. PMID- 20355769 TI - Supercritical gel drying: a powerful tool for tailoring symmetric porous PVDF-HFP membranes. AB - In this work, poly(vinylidene fluoride) copolymer with hexafluoropropylene (PVDF HFP) membrane-like aerogels have been generated for the first time. PVDF-HFP gels have been prepared from polymer-acetone solutions by adding various amounts of ethanol. A series of supercritical drying experiments have been performed at different pressures (from 100 to 200 bar) and temperatures (from 35 to 45 degrees C) and at various polymer concentrations (from 5 to 12 wt %). The effects of the process conditions on the membrane morphology have been evaluated, and structure property relationships have been found. In all cases, the membranes exhibit interconnected structures with nanosized pores and high porosity, leading to reduced resistance to the gas mass transfer and high hydrophobic character of the surfaces. These membrane-like aerogels promise to form a new class of highly hydrophobic porous interfaces, potentially suitable to be used in membrane operations based, for example, on the contactor technology. PMID- 20355770 TI - Fabrication of SWNT/silica composites by the sol-gel process. AB - Single-walled carbon nanotubes (SWNTs) have successfully been incorporated into a silica matrix using the sol-gel process. The SWNTs were first functionalized with 3-aminopropyltriethoxysilane (APTES) through an amide linkage formed between the carboxylic acid groups already present on their surface and the amino group on APTES. The silane moieties were then used to form silica with and without the presence of tetramethylorthosilicate (TMOS) in a sol-gel reaction. The addition of TMOS was found to influence the molecular arrangement of the SWNT in the silica matrix and also to retard the degradation of the silica-SWNT composite. PMID- 20355771 TI - Beam-surface scattering studies of the individual and combined effects of VUV radiation and hyperthermal O, O2, or Ar on FEP Teflon surfaces. AB - Beam-surface scattering experiments were used to probe products that scattered from FEP Teflon surfaces during bombardment by various combinations of atomic and molecular oxygen, Ar atoms, and vacuum ultraviolet (VUV) light. A laser-breakdown source was used to create hyperthermal (translational energies in the range 4-13 eV) beams of argon and atomic/molecular oxygen. The average incidence energy of these beams was tunable and was controlled precisely with a synchronized chopper wheel. A filtered deuterium lamp provided a source of VUV light in a narrow wavelength range centered at 161 nm. Volatile products that exited the surfaces were monitored with a rotatable mass spectrometer detector. Hyperthermal O atoms with average translational energies above approximately 4 eV may react directly with a pristine FEP Teflon surface, and the reactivity appears to increase with the translational energy of the incident O atoms. VUV light or highly energetic collisions of O2 or Ar may break chemical bonds and lead to the ejection of volatile products; the ejection of volatile products is enhanced when the surface is subjected to VUV light and energetic collisions simultaneously. Exposure to VUV light or to hyperthermal O2 or Ar may increase the reactivity of an FEP Teflon surface to O atoms. PMID- 20355772 TI - Magnetic-resonance evaluation of the suitability of microstructured polymer optical fibers as sensors for ionic aqueous solutions. AB - Nuclear magnetic resonance was used to probe the distribution of water and ionic species in a microstructured poly(methyl methacrylate) (PMMA) polymer optical fiber (MPOF), with a plan to assess the suitability of these fibers for aqueous chemosensing. The NMR spectra and the measurements of proton spin relaxation in hydrated fibers demonstrated the presence of two distinct pools of water: water residing in the microstructure channels and the hydration water residing in the polymer matrix of the fiber. No facile chemical exchange between these two pools was present. The NMR peaks of the two pools of water were separated by 1.53 ppm. Relaxation measurements of the fiber samples doped with aqueous copper sulfate showed that charged ions freely entered the microstructure channels but were completely excluded from the polymer matrix of the fiber. Measurements of the apparent diffusion coefficient of water along the axial direction of the fiber showed that water molecules moved unimpeded along the channels. This is the first reported magnetic-resonance study of microstructured optical fibers. The findings suggest that microstructured PMMA fibers are compatible with ionic aqueous solutions and could provide a robust and durable platform for chemical-sensing applications. PMID- 20355773 TI - Latent synthesis of electrically conductive surface-silvered polyimide films. AB - A facile ambient temperature route to the fabrication of surface silver metallized polyimide films is described. Silver(I) trifluoromethanesulfonate or silver(I) nitrate and a polyimide, derived from 2,2-bis(3,4 dicarboxyphenyl)hexafluoropropane dianhydride and an equimolar amount of 4,4' oxydianiline and 3,5-diaminobenzoic acid, were dissolved together in dimethylacetamide. Silver(I)-doped films were prepared at thicknesses of 25-40 microm and depleted of solvent by evaporation at ambient temperature and low humidity. The silver(I)-ion-containing films were then treated with aqueous solutions of the reducing agents hydrazine hydrate and hydroxylamine, which brought forth surface-silvered films exhibiting conductivity on the order of bulk polycrystalline silver accompanied by modest-to-high specular reflectivity. PMID- 20355774 TI - Hyperbranched aliphatic polyesters and reactive diluents in thermally cured coil coatings. AB - Two hydroxy-functional hyperbranched aliphatic polyesters based on 2,2 dimethylolpropionic acid (bis-MPA) and a partially aromatic conventional polyester have been studied as thermoset resins for solvent-borne thermally cured polyester cross-linked with melamine coatings for precoated sheet metal, i.e., coil coatings. The hyperbranched polyesters differ with respect to the ratio of the end groups, being either hydroxyls or alkyl esters. The rheological properties of formulations with different polyester resin composition and reactive diluent, i.e., rape seed methyl ester, content have been evaluated with viscosity measurements. Films cured either under industrial cure conditions to obtain a peak metal temperature of 232-241 degrees C or at a lower temperature, i.e., 130 degrees C, on untreated or organic primer-coated hot-dipped-galvanized steel substrates have been prepared. The film properties have been evaluated with differential scanning calorimetry and conventional film characterization techniques, i.e., adhesion, impact, Erichsen cupping, pencil hardness, microhardness, and scratch and chemical resistance tests. Formulations possessing high drying ability with maintained suitable film application viscosity were obtained using a hyperbranched polyester resin and a reactive diluent. It is proposed that a solvent-free polyester/melamine formulation with sufficient film properties to withstand the rough forming procedures associated with coil coatings can be obtained by further modification of the resin and greater amounts of reactive diluent. PMID- 20355775 TI - Comparative performance of electrospun collagen nanofibers cross-linked by means of different methods. AB - Collagen, as the major structural protein of the extracellular matrix in animals, is a versatile biomaterial of great interest in various engineering applications. Electrospun nanofibers of collagen are regarded as very promising materials for tissue engineering applications because they can reproduce the morphology of the natural bone but have as a drawback a poor structural consistency in wet conditions. In this paper, a comparative study between the performance of different cross-linking methods such as a milder enzymatic treatment procedure using transglutaminase, the use of N-[3-(dimethylamino)propyl]-N' ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, and genipin, and the use of a physical method based on exposure to ultraviolet light was carried out. The chemical and enzymatic treatments provided, in this order, excellent consistency, morphology, cross-linking degree, and osteoblast viability for the collagen nanofibers. Interestingly, the enzymatically cross-linked collagen mats, which are considered to be a more biological treatment, promoted adequate cell adhesion, making the biomaterial biocompatible and with an adequate degree of porosity for cell seeding and in-growth. PMID- 20355776 TI - Cross-laboratory experimental study of non-noble-metal electrocatalysts for the oxygen reduction reaction. AB - Nine non-noble-metal catalysts (NNMCs) from five different laboratories were investigated for the catalysis of O(2) electroreduction in an acidic medium. The catalyst precursors were synthesized by wet impregnation, planetary ball milling, a foaming-agent technique, or a templating method. All catalyst precursors were subjected to one or more heat treatments at 700-1050 degrees C in an inert or reactive atmosphere. These catalysts underwent an identical set of electrochemical characterizations, including rotating-disk-electrode and polymer electrolyte membrane fuel cell (PEMFC) tests and voltammetry under N(2). Ex situ characterization was comprised of X-ray photoelectron spectroscopy, neutron activation analysis, scanning electron microscopy, and N(2) adsorption and its analysis with an advanced model for carbonaceous powders. In PEMFC, several NNMCs display mass activities of 10-20 A g(-1) at 0.8 V versus a reversible hydrogen electrode, and one shows 80 A g(-1). The latter value corresponds to a volumetric activity of 19 A cm(-3) under reference conditions and represents one-seventh of the target defined by the U.S. Department of Energy for 2010 (130 A cm(-3)). The activity of all NNMCs is mainly governed by the microporous surface area, and active sites seem to be hosted in pore sizes of 5-15 A. The nitrogen and metal (iron or cobalt) seem to be present in sufficient amounts in the NNMCs and do not limit activity. The paper discusses probable directions for synthesizing more active NNMCs. This could be achieved through multiple pyrolysis steps, ball milling steps, and control of the powder morphology by the addition of foaming agents and/or sulfur. PMID- 20355777 TI - Flexible and transparent SWCNT electrodes for alternating current electroluminescence devices. AB - The application of transparent single-walled carbon nanotube (SWCNT) electrodes in rigid and flexible alternating current electroluminescence (ACEL) devices is demonstrated. SWCNT thin-film electrodes (50-160 nm) were made using a spray coating process suitable for adjusting the transparency and sheet resistance. The dispersing procedure was optimized by comparing the transparency to sheet resistance ratio (T/R) of the electrodes. The emission intensity was as high as that for indium-tin oxide (ITO)-based ACEL devices with transparencies comparable to those of ITO-coated polymer slides. PMID- 20355778 TI - Novel dye-sensitized solar cell architecture using TiO2-coated vertically aligned carbon nanofiber arrays. AB - A novel dye-sensitized solar cell (DSSC) architecture based on vertically aligned carbon nanofibers coated with a thin nanoneedle-textured anatase TiO2 film is demonstrated. An encouraging overall conversion efficiency of approximately 1.09% and a rather high open-circuit voltage of approximately 0.64 V have been achieved. The efficient charge separation at the TiO2-CNF junction and the large outer TiO2 surface of this core-shell architecture provide new methods to tune the materials and interfaces in solar cells. PMID- 20355779 TI - Compatibilization by homopolymer: significant improvements in the modulus and tensile strength of PPC/PMMA blends by the addition of a small amount of PVAc. AB - Poly(propylene carbonate) (PPC), a polymer produced from CO2, has been melt-mixed with 30 wt % poly(methyl methacrylate) (PMMA) with the aim of enhancing the physical properties of PPC for practical use but keeping a relatively high CO2 fixing rate in the compound. The observation of a coarse phase structure with a large PMMA domain size and a large size distribution in the blend indicates the immiscibility between PPC and PMMA. The addition of a small amount of poly(vinyl acetate) (PVAc) not only shifts the glass transition temperatures (T(g)'s) of both PPC and PMMA markedly but also significantly increases the modulus and tensile strength of the blend. The prepared compound with 5 per hundred parts of resin PVAc shows a 26 times higher elastic modulus and an approximately 3.8 times higher tensile strength than pure PPC at room temperature. The morphological investigation indicates that the incorporation to PVAC not only induces the finer dispersion of PMMA in the PPC matrix but also results in the phase transformation from a sea-island to a co-continuous structure. PMID- 20355780 TI - Spray-coated fluorine-free superhydrophobic coatings with easy repairability and applicability. AB - The present paper reports a very simple and low-cost fluorine-free superhydrophobic coating prepared by spray-coating metal alkylcarboxylates, for example, Cu[CH(3)(CH(2))(10)COO](2), onto virtually any substrates. Superhydrophobicity with a static water contact angle of about 160 degrees and a sliding angle of 5 degrees was achieved from the proper precursor concentration. The advantages of the present approach include the cheap and fluorine-free raw materials, environmentally benign solvents, an industrial implementation method, and easy repairability and applicability so as to make a great application potential in practice. The hydrophobicity of coatings and the adhesion to water were found to be dependent on the surface morphology that was governed by the precursor concentrations from which coatings were prepared. The static wetting behavior of water droplets with different sizes gentlly deposited on the coatings was studied in more detail and correlated to theories, i.e., Wenzel's and Cassie's models. The results indicated that nanoribbon-textured coatings prepared from low precursor concentration (0.02 M) exhibited a transition from the metastable Cassie-Baxter state to the Wenzel state with increments in the droplet volume, and eventually droplets firmly stick to the surface even when the droplet was gently deposited on the surface. Surface coatings with dual roughness at both microscale and nanometer scale were formed as the concentration (0.04 M) was increased and conferred a stable Cassie state, even for increased droplet size and increased droplet deposit speed. PMID- 20355781 TI - An investigation on the capillary wetting of glass fiber tow and fabric structures with nanoclay-enriched reactive epoxy and silicone oil mixtures. AB - Capillary wetting of a biaxially-oriented glass fabric and the tow comprising the fabric was examined via the Washburn equation with silicone oil and a reactive epoxy-curative system containing 0-4 wt % nanoclay reinforcement. Capillary wetting of silicone oil was used to measure the hydraulic constant of the fabric and tow. The wetting rates for fabric were found to be greater than those for tow and this was based on the larger pore radii of fabric compared to tow. Reynolds and capillary numbers calculated from wetting rate data indicated that the flow is dominated by interfacial tension. The presence of nanoclay offered a significant perturbation to capillary wetting behavior. Wetting rates indicate that the effect of nanoclay is 2-fold: blocking of tow pores and increasing the wetted area. This suggests that nanoclay particles are aggregating and the flow field is such that the particles are not dispersed additionally under the present conditions. Capillary wetting rates of fabric and tow samples were measured with reactive epoxy-amine mixtures at various nanoclay loadings. The presence of nanoclay offers another level of complexity to the Washburn equation. In addition to the liquid/fabric or tow interfacial tension, the interfacial tension of the liquid/nanoclay interface has to be reconciled. As a consequence, hydraulic constant, surface tension, and contact angle are convoluted in such a binary system. PMID- 20355782 TI - The structure of oleamide films at the aluminum/oil interface and aluminum/air interface studied by Sum Frequency Generation (SFG) vibrational spectroscopy and Reflection Absorption Infrared Spectroscopy (RAIRS). AB - The structure of oleamide (cis-9-octadecenamide) films on aluminum has been investigated by sum frequency generation vibrational spectroscopy (SFG) and reflection absorption infrared spectroscopy (RAIRS). Three different film deposition strategies were investigated: (i) films formed by equilibrium adsorption from oleamide solutions in oil, (ii) Langmuir-Blodgett films cast at 1 and 25 mN m(-1), (iii) thick spin-cast films. Both L-B and spin-cast films were examined in air and under oil. The adsorbate formed in the 1 mN m(-1) film in air showed little orientational order. For this film, the spectroscopic results and the ellipsometric thickness point to a relatively conformationally disordered monolayer that is oriented principally in the plane of the interface. Direct adsorption to the metal interface from oil results in SFG spectra of oleamide that are comparable to those observed for the 1 mN m(-1) L-B film in air. In contrast, SFG and RAIRS results for the 25 mN m(-1) film in air and SFG spectra of the spin-cast film in air both show strong conformational ordering and orientational alignment normal to the interface. The 25 mN m(-1) film has an ellipsometric thickness almost twice that of the 1 mN m(-1) L-B film. Taken in combination with the spectroscopic results, this is indicative of a well packed monolayer in air in which the hydrocarbon chain is in an essentially defect-free extended conformation with the methyl terminus oriented away from the surface. A similar structure is also deduced for the surface of the spin-cast film in air. Upon immersion of the 25 mN m(-1) L-B film in oil the SFG spectra show that this film rapidly adopts a relatively disordered structure similar to that seen for the 1 mN m(-1) L-B film in air. Immersion of the spin-cast film in oil results in the gradual disordering of the amide film over a period of several days until the observed spectra become essentially identical to those observed for direct adsorption of oleamide from oil. PMID- 20355783 TI - Preparation of evaporation-resistant aqueous microdroplet arrays as a model system for the study of molecular order at the liquid/air interface. AB - Aqueous arrays of microdroplets typically sized between 2 and 10 microm were generated by microfluid contact printing and stabilized with respect to evaporation by incorporation of poly(ethylene oxide). The arrays are used as a model system for the study of structure formation at liquid/air or liquid/liquid interfaces. In particular, we demonstrated the self-organization of fatty acids with photopolymerizable diacetylene units (10,12-pentacosadiynoic acid) at the liquid/air interface of the microdroplets. Topochemical polymerization behavior of this compound and the autofluorescence property of the resulting polyconjugated polymer are appropriate features to prove the molecular order of the amphiphilic molecules at the interface. PMID- 20355784 TI - Quantitative investigation of the photodegradation of polyethylene terephthalate film by friction force microscopy, contact-angle goniometry, and X-ray photoelectron spectroscopy. AB - Studies of the UV-induced photodegradation of poly(ethylene terephthalate) (PET) have been carried out using contact-angle goniometry, X-ray photoelectron spectroscopy (XPS), and friction force microscopy (FFM). The advancing contact angle of water, theta, decreased following exposure of free-standing PET films to UV light. Measurements of surface friction by FFM showed that the coefficient of friction mu increased as the degradation proceeded, reaching a limiting value after ca 200 min, in agreement with the contact angle data. Using a modified form of the Cassie equation, a quantitative analysis of the extent of modification could be carried out. There was a very close correlation between the coefficient of friction determined by FFM and the value of cos theta. XPS provided more detailed information on surface bonding that also correlated closely with the FFM data. Although FFM provides quantitative data on surface modification with nanometer-scale spatial resolution, it does not provide detailed structural information such as is provided by XPS. The oxygen content at the surface was found to increase as photo-generated radicals within the PET reacted with atmospheric oxygen. Increases in both ester and carbonyl contributions within XPS data accompanied this increase. It was concluded that the photodegradation process follows mainly Norrish type I reaction pathways, following previous work by Fechine et al and Grosstete et al. PMID- 20355785 TI - Biomimetic ultrathin whitening by capillary-force-induced random clustering of hydrogel micropillar arrays. AB - Capillary-force-induced collapse of high-aspect-ratio microstructures has often been considered a failure mechanism in device fabrication. Here, we study capillary-force-induced clustering behavior of highly ordered hydrogel micropillar arrays from 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) and explore their utility as ultrathin whitening layers (less than 9 mum thick). When exposed to water, followed by drying in an air stream, the micropillars were softened, bent, and randomly clustered together because of competition between the capillary force and elastic restoring force of the pillars. By varying the relative composition of the water-swellable PHEMA and glassy PMMA, we modulated the elastic modulus of the pillars in the wet state spanning over 3 orders of magnitude. By minimizing the sum of the capillary meniscus interaction energy and the elastic bending energy of the pillars for a cluster, we estimated the average cluster size as a function of the elastic modulus of the pillars, which agreed well with the experimental observation. The randomly clustered micropillar arrays appeared white in color because of random light scattering from the clusters, similar to the observation in the white beetles, whose scales consist of a few micrometer-thick random networks of microfilaments. PMID- 20355787 TI - Novel p-phenylenevinylene compounds containing thiophene or anthracene moieties and cyano-vinylene bonds for photovoltaic applications. AB - Two novel soluble compounds T and A that contain a central dihexyloxy-p phenylenevinylene unit, intermediate moieties of thiophene or anthracene, respectively, and terminal cyano-vinylene nitrophenyls were synthesized and characterized. They showed moderate thermal stability and relatively low glass transition temperatures. These compounds displayed similar optical properties. Their absorption was broad and extended up to about 750 nm with the longer wavelength maximum around 640 nm and an optical band gap of approximately 1.70 eV. From the current-voltage characteristics of the devices using both compounds T and A, it was concluded that both compounds behave as p-type organic semiconductors with hole mobility on the order of 10(-5) cm(2)/(V s). The power conversion efficiency (PCE) of the devices based on these compounds was 0.019% and 0.013% for compounds A and T, respectively. When compounds A and T were blended with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), the PCE dramatically increased up to 1.66% and 1.36% for devices with A:PCBM and T:PCBM, respectively. The efficiencies of the devices were further enhanced upon thermal annealing up to 2.49% and 2.33% for devices based on A:PCBM and T:PCBM, respectively. PMID- 20355786 TI - Remote near-IR light activation of a hyaluronic acid/poly(l-lysine) multilayered film and film-entrapped microcapsules. AB - Spontaneous embedding of gold nanoparticle (NP) aggregates or polyelectrolyte microcapsules modified with NPs in biocompatible hyaluronic acid/poly(l-lysine) films is reported. The NPs were adsorbed in the aggregated state to induce near IR light absorption. The films functionalized with gold NPs become active in response to a "biologically friendly" near-IR laser at a power of about 20 mW. The activation is characterized by a localized temperature increase in the film, allowing conversion of light energy to heat into confined volumes. Microcapsules adsorbed onto the film can release its cargo under stimulation with near-IR light because of localized permeability changes in their walls. This work is aimed at layer-by-layer film-based biomedical coatings and active surfaces with light sensitive features wherein metal NPs and microcapsules are used as active centers or carriers with remote control of functionalities. PMID- 20355788 TI - Biodegradable polyesters as crystallization-accelerating agents of poly(l lactide). AB - A series of biodegradable polyesters, poly[(R)-3-hydroxybutyrate] (PHB), poly( caprolactone) (PCL), and polyglycolide (PGA), were found to be effective crystallization-accelerating agents for poly(l-lactide) (PLLA). Differential scanning calorimetry and polarized optical microscopy strongly suggested that the accelerated crystallization of PLLA in the presence of the three biodegradable polyesters is attributable to a nucleation-assisting effect of PCL and PGA and a spherulite growth-accelerating effect of PHB, although the incorporated PHB lowered the spherulite number of PLLA per unit area. The spherulite growth accelerating effect of PHB probably resulted from the relatively high miscibility of PLLA with PHB and the low glass transition temperature of PHB compared to that of PLLA. The crystallization kinetics of PLLA varied only in the case of PLLA/PHB blends during cooling from the melt, as evidenced by the nucleation constant and radius growth rate values of the spherulites. The nucleation and growth types of PLLA crystallites are thought to be altered only in the case of PLLA/PGA blends during heating, as evidenced by Avrami exponent n values. PMID- 20355789 TI - Multiple alignment modes for nematic liquid crystals doped with alkylthiol-capped gold nanoparticles. AB - The ability of alkylthiol capped gold nanoparticles (Au NPs) to tune, alter, and reverse the alignment of nematic liquid crystals (LCs) has been investigated in detail. Adjusting the concentration of the suspended Au NPs in the nematic LC host, optimizing the sample preparation protocol, or providing different sample substrates (untreated glass slides, rubbed polyimide-coated LC test cell, or ITO coated glass slides) results in several LC alignment scenarios (modes) including vertical alignment, planar alignment, and a thermally controlled alignment switch between these two alignment modes. The latter thermal switch between planar and homeotropic alignment was observed particularly for lower concentrations (i.e., around 1 to 2 wt %) of suspended NPs in the size regime of 1.5-2 nm and was found to be concentration-dependent and thermally reversible. Different scenarios are discussed that could explain these induced alignment modes. In one scenario, the NP-induced alignment is related to the temperature-dependent change of the order parameter, S, of the nematic phase (ordering in the bulk). In the second scenario, a change of the ordering of the nematic molecules around the NPs that reside at the interfaces is described. We also started to test spin coating as an alternative way of preparing nematic thin films with well-separated Au NPs on the substrate and found this to be a possible method for manufacturing of future NP doped LC devices, as this method produced evenly distributed NPs on glass substrates. Together the presented findings continue to pave the way for LC display-related applications of Au NP-doped nematic LCs and provide insights for N-LC sensor applications. PMID- 20355790 TI - Phenomenology of photoinduced processes in the ionic sol-gel-based azobenzene materials. AB - Very recently, supramolecular azobenzene-containing materials have been demonstrated to be effective for holographic inscription of surface relief gratings. High efficiency of grating formation in these materials is advantageously combined with easy material preparation because of the supramolecular principle of building blocs combination, availability of chemical components, and good film-forming properties. The materials show great promise for wide optical applications. Here, one type of material formulation based on ionic complexes of poly(aminosiloxane) is experimentally investigated concerning the induction of birefringence, efficiency of relief formation, and thermal stability of surface structures. Properties of the material were changed on the molecular level by varying the azobenzene content and on the macro level by varying chemical processing conditions. The results are discussed in terms of cross-linking and plasticizing effects caused by residual solvent and the low molecular-weight azobenzene component. An improvement of both the efficiency of grating formation and their thermal stability by these means has been demonstrated. The results can be adapted to other azobenzene-containing materials. In addition, a drastic change of films solubility has been observed upon irradiation. PMID- 20355791 TI - Assembled surface-anisotropic colloids as a template for a multistage catalytic membrane reactor. AB - A polymeric catalytic membrane reactor (CMR) is fabricated using alternating assemblies of surface-anisotropic (sa-) and plain (p-) polystyrene (PS) colloids as a template. We report the preparation of TiO2 sa-PS colloids by physical vapor deposition of titanium onto a colloidal monolayer in an oxygen-rich environment and employ the modified colloids as a means to deliver the TiO2 catalyst to the CMR pores. sa-PS and p-PS colloids are assembled into alternating cylindrical sections inside a microcapillary followed by infiltration and curing of a liquid polymer precursor in the interstitial space of the assembly. Subsequent organic solvent treatment results in a cylindrical porous CMR with embedded TiO2 caps. TiO2 cap embedment, composition and surface morphology, surface pore structure, and cross-sectional integrity are analyzed using variable-pressure scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. PMID- 20355792 TI - Fabrication and characterization of a sialoside-based carbohydrate microarray biointerface for protein binding analysis with surface plasmon resonance imaging. AB - Monitoring multiple biological interactions in a multiplexed array format has numerous advantages. However, converting well-developed surface chemistry for spectroscopic measurements to array-based high-throughput screening is not a trivial process and often proves to be the bottleneck in method development. This paper reports the fabrication and characterization of a new carbohydrate microarray with synthetic sialosides for surface plasmon resonance imaging (SPRi) analysis of lectin-carbohydrate interactions. Contact printing of functional sialosides on neutravidin-coated surfaces was carried out and the properties of the resulting elements were characterized by fluorescence microscopy and atomic force microscopy (AFM). Sambucus nigra agglutinin (SNA) was deposited on four different carbohydrate functionalized surfaces and differential binding was analyzed to reveal affinity variation as a function of headgroup sialic acid structures and linking bonds. SPRi studies indicated that this immobilization method could result in high quality arrays with RSD < 5% from array element to array element, superior to the conventional covalent linkage used for protein cholera toxin (CT) in a comparison experiment, which yields nonuniform array elements with RSD > 15%. Multiplexed detection of SNA/biotinylated sialoside interactions on arrays up to 400 elements has been performed with good data correlation, demonstrating the effectiveness of the biotin-neutravidin-based biointerface to control probe orientation for reproducible and efficient protein binding to take place. Additionally, the regeneration of the array surface was demonstrated with a glycine stripping buffer, rendering this interface reusable. This in-depth study of array surface chemistry offers useful insight into experimental conditions that can be optimized for better performance, allowing many different protein-based biointeractions to be monitored in a similar manner. PMID- 20355793 TI - Improved morphology and performance from surface treatments of naphthalenetetracarboxylic diimide bottom contact field-effect transistors. AB - We report bottom contact organic field-effect transistors (OFETs) with various surface treatments based on n-channel materials, specifically, 1,4,5,8 naphthalene-teracarboxylic diimides (NTCDIs) with three different fluorinated N substituents, systematically studied with a particular emphasis on the interplay between the morphology of the organic semiconductor films and the electrical device properties. The morphological origins of the improvements were directly and dramatically visualized at the semiconductor-contact interface. As a result of a series of treatments, a large range of performances of bottom contact side chain-fluorinated NTCDI OFETs (mobility from 1 x 10(-6) to 8 x 10(-2) cm(2)/(V s), on/off ratio from 1 x 10(2) to 1 x 10(5)) were obtained. The surface treatments enabled systems that had shown essentially no OFET activity without electrode modification activity to perform nearly as well as top contact devices made from the same materials. In addition, for the fresh bottom contact NTCDI device, the effect of gate bias stress on the tens-of-minutes time scale, during which the threshold voltage (V(t)) shifted and relaxed with similar time constants, was observed. PMID- 20355794 TI - Cluster beam deposition of lead sulfide nanocrystals into organic matrices. AB - Lead sulfide nanocrystals (PbS NCs) were codeposited into two organic films, titanyl phthalocyanine (TiOPc) and alpha-sexithiophene, using cluster beam deposition (CBD). NCs of average diameters of approximately 3-4 nm were evenly distributed in these organic films with average particle spacings of approximately 4 nm, as determined by transmission electron microscopy. The film composition and NC surface chemistry were monitored by X-ray photoelectron spectroscopy (XPS) and other methods. Pb:S stoichiometry in the NC/TiOPc film was determined by XPS to correspond to the PbS cubic rock salt structure. Soft-XPS using 200 eV energy photons determined the NC-organic surface chemistry by resolving the S 2p core level into four distinct components for sulfur. The soft XPS results found that the PbS NC surface chemistry could be tuned by varying the H(2)S/Ar gas ratio within the CBD source. PMID- 20355795 TI - Water-based oxygen-sensor films. AB - The luminescent cyclometalated iridium complex [Ir(fppy)(2)(t-Bu iCN)(2)]CF(3)SO(3), 1 (fppy = 4-(2-pyridyl)benzaldehyde, and t-Bu-iCN = tert butyl isocyanide), was synthesized and characterized by X-ray crystallography and (1)H NMR, absorption, and emission spectroscopies. Complex 1 was quantitatively bound to the water-soluble amine-functionalized polymer Silamine D208-EDA by reductive amination, to produce 2. The quantum yield of emission and excited state lifetime of 2 (varphi(em) = 0.23 and tau = 20.6 mus) are comparable to that of the model complex [Ir(tpy)(2)(t-Bu-iCN)(2)]CF(3)SO(3), 3 (tpy = 2-(p- tolyl) pyridine) with varphi(em) = 0.28 and tau = 35.6 mus. Aqueous blends of 2 with Silamine and colloidal microcrystalline cellulose (MC) were used to prepare oxygen-sensor films. Oxygen sensitivities of these films were determined as a function of Silamine:MC ratio and obeyed Stern-Volmer kinetics. The optimum oxygen-sensor film composition was 2 in 1:1 Silamine:MC, which had an oxygen sensitivity of 0.502 over an atmospheric pressure range of 0.007-45 psi. Temperature sensitivity (percentage loss of intensity per degrees C) of this film was determined to be -1.1 and -1.4% degrees C(-1) at vacuum and 1 bar atmospheric pressure, respectively. These results were compared to those of films incorporating dispersions of 1 and 3. Luminescence microscopy of 9:1, 1:1, and 1:5 Silamine:MC films of 2 show that the charged iridium complex in 2 associates with the surface of MC and lifetime measurements of these films show an increase in lifetime with increasing MC fraction. The optimum quenching sensitivity observed for the 1:1 Silamine:MC film suggests that the diffusion of oxygen must decrease with increasing fraction of MC and thereby decrease oxygen sensitivity. These novel materials offer an environmentally friendly alternative to the preparation of oxygen-sensor films. PMID- 20355796 TI - Comparison of methods for generating planar DNA-modified surfaces for hybridization studies. AB - The surface conformation and accessibility of oligonucleotides within arrays are two key parameters that affect the utility of immobilized nucleic acids in sensor technologies. In this work, a novel combination of analytical techniques was used to compare two methods for DNA immobilization on glass. The aim of the study was to identify a method that generated a high surface density of hybridization accessible oligonucleotides in a true planar monolayer. The first method based on direct coupling of silanized DNA to the glass surface showed a high immobilization density of 0.013 molecules/nm2 but low surface accessibility, as shown by the hybridization measurements (< or =15%). The second method, based on the biotin-streptavidin interaction, generated a high immobilization density (0.02 molecules/nm2) and high surface accessibility (90%). Atomic force microscopy and X-ray photoelectron spectroscopy indicated that both methods achieved uniform surfaces. Using the biotin-streptavidin system, the intermolecular distance between the hybridized molecules could be tightly controlled by titrating biotinylated complementary and noncomplementary oligonucleotides. PMID- 20355797 TI - Synthesis and nonlinear optical properties of a peripherally functionalized hyperbranched polymer by DR1 chromophores. AB - The first peripheral postfunctionalization of a hyperbranched polyimide by nonlinear optic chromophores (DR1 derivative) was achieved using two different routes. The first one consists in the esterification of the terminal carboxylic acid groups, whereas the second is based on copper-catalyzed Huisgen reaction of the terminal propargylic ester groups. The resulting polymers display good solubility in classical organic solvents and good filmability because thick films can be prepared (up to 2.7 mum). The second-order nonlinear optical properties were measured by SHG at 1064 nm and we show that these hyperbranched polymers exhibit good poling efficiency and good thermal stability since the electro-optic activity remains stable up to 130 degrees C. These results illustrate the potential of hyperbranched polymers to host second-order nonlinear optical chromophores to replace dendrimers or classical linear polymers generally used in this area. PMID- 20355798 TI - Physicochemical investigation of pulsed laser deposited carbonated hydroxyapatite films on titanium. AB - Carbonated hydroxyapatite (CHA)-coated titanium can find wide applications as bone substitute implant in bone and dental surgery and orthopedics, promoting osseointegration with a host bone and ensuring biocompatibility and bioactivity. In this work, carbonated hydroxyapatite films were prepared on titanium substrates by pulsed laser deposition at different substrate temperatures ranging from 30 to 750 degrees C. The properties of films were investigated by scanning electron microscopy, atomic force microscopy, energy-dispersive X-ray diffraction, and Fourier transform infrared spectroscopy. Vickers microhardness measurements of the composite film-substrate systems were performed, and the intrinsic hardness of films was separated from the composite hardness using a "law-of-mixtures" approach and taking into account the indentation size effect. The prepared CHA films are nearly stoichiometric with a Ca/P atomic ratio of 2.0 2.2. The films deposited in the 30-500 degrees C temperature range are about 9 microm thick, amorphous, having an average roughness of 60 nm. At higher temperature, 700-750 degrees C, the films are about 4 microm thick, show a finer surface morphology and an average roughness of 20 nm. At 750 degrees C the films are amorphous, whereas at 700 degrees C they are crystalline and textured along the (202) and (212) directions. The intrinsic hardness of the films increased with an increase in substrate temperature, being as low as 5 GPa at 30 degrees C and reaching a high value of 28 GPa at 700 degrees C. The rich information gained by the joint use of the mentioned techniques allowed a comprehensive characterization of this system. PMID- 20355799 TI - Coating individual single-walled carbon nanotubes with nylon 6,10 through emulsion polymerization. AB - Solvent microenvironments are formed around individual single-walled carbon nanotubes (SWNTs) by mixing SWNT suspensions with water-immiscible organic solvents. These microenvironments are used to encapsulate the SWNTs with the monomer sebacoyl chloride. Hexamethylene diamine is then injected into the aqueous phase so the formation of nylon 6,10 is restricted to the interface between the microenvironment and water. This emulsion polymerization process results in uniform coatings of nylon 6,10 around individual SWNTs. The nylon coated SWNTs remain dispersed in the aqueous phase and are highly luminescent at pH values ranging from 3 to 12. This emulsion polymerization method provides a general approach to coat nanotubes with various polymers. PMID- 20355800 TI - Zinc oxide nanowire interphase for enhanced interfacial strength in lightweight polymer fiber composites. AB - A novel functionalization method for aramid fibers is developed to enhance the bonding of a ZnO nanowire interphase grown on the fiber surface for interfacial strength enhancement. The nanowire interphase functionally grades the typically discrete interface and reduces the stress concentration between the fiber and matrix. The functionalization process is developed to improve the bonding between the ZnO nanowires and the aramid fiber and is validated through Fourier transform IR and X-ray photoelectron spectroscopy studies. Mechanical testing shows significant improvement in the interfacial shear strength with no decrease in the base fiber strength. This is the only technique found in the literature for the growth of a nanowire interphase on polymer fibers for structural enhancement without degrading the in-plane properties of the bulk composite. Furthermore, it is firmly shown that the functionalization process is a necessary condition for enhanced interfacial strength, demonstrating that ZnO nanowires strongly interact with carboxylic acid functional groups. PMID- 20355801 TI - Enantioselective separation using chiral mesoporous spherical silica prepared by templating of chiral block copolymers. AB - In this work, we synthesized chiral mesoporous silica (CMS) spheres, which can be used as a potential candidate for chiral separation. The CMS spheres with controllable pore sizes (of 2-3 nm) and high surface areas of ca. 614 m(2) g(-1) were synthesized by chiral templating with chiral block copolymers based on poly(ethylene oxide) and dl-glutamic acid [PEO(113)-b-(GluA)(10)]. The ordered structure of the chiral mesopores was characterized by high-resolution transmission electron microscopy, and the average pore diameters of chiral mesopores were estimated from the nitrogen adsorption-desorption measurements. The enantioselectivity properties and chiral resolution kinetics of the mesopores of silica spheres, after extraction of chiral polymers of PEO(113)-b-(l/d GluA)(10), were scrutinized using a racemic solution of valine and measuring the circular dichroism and optical polarimetery. A chiral selectivity factor of 5.22 was found with a specific enantiomer of valine adsorbed preferably. These results raise the new possibilities of CMS spheres for enantiomeric separation and other enantioselective applications. PMID- 20355802 TI - Sol-gel-derived iron oxide thin films on silicon: surface properties and interfacial chemistry. AB - Uniform high-quality iron oxide thin films can be formed from the spin coating of iron oxide/hydroxide sol-gels on a silicon substrate. Thermal processing of the films at temperatures of approximately 300 degrees C results in the transformation of films into a ternary layered structure with iron oxide, Fe(2)O(3), at the surface, characterized by Mossbauer spectroscopy, and reduced, metallic iron characterized by depth profiling of the surface by X-ray photoelectron spectroscopy as a function of Ar(+) etching. Imaging of the etched surface by scanning electron microscopy reveals two distinct regions at the interface, nanoparticles that are very iron-rich separated by an unstructured region that is somewhat less iron-rich. The results demonstrate a synthetic protocol for the spontaneous formaton of a ternary layered structure from a simple one-step preparation. PMID- 20355803 TI - Magnetically responsive calcium carbonate microcrystals. AB - Here we report the fabrication of magnetically responsive calcium carbonate microcrystals produced by coprecipitation of calcium carbonate in the presence of citrate-stabilized iron oxide nanoparticles. We demonstrate that the calcite microcrystals obtained possess superparamagnetic properties due to incorporated magnetite nanoparticles and can be manipulated by an external magnetic field. The microcrystals doped with magnetic nanoparticles were utilized as templates for the fabrication of hollow polyelectrolyte microcapsules, which retain the magnetic properties of the sacrificial cores and might be spatially manipulated using a permanent magnet, thus providing the magnetic-field-facilitated delivery and separation of materials templated on magnetically responsive calcite microcrystals. PMID- 20355804 TI - Reduced efficiency roll-off in organic light-emitting diodes by a novel short lived organoeuropium emitter. AB - In this paper, we report a novel organoeuropium complex [Eu(DPDBM)(3)DPPZ] based on a triphenylamine-derived beta-diketone ligand for short-lived emitter exploration. The (5)D(0) --> (7)F(2) ( approximately 610 nm) luminescence lifetime of Eu(DPDBM)(3)DPPZ is only 30 mus, which is 1 order of magnitude shorter than that of a typical Eu(3+) complex. The electroluminescence device using Eu(DPDBM)(3)DPPZ as the emitter achieves a maximum current efficiency of 3.0 cd/A, and the efficiency roll-off is largely reduced because of the emitter's short luminescence lifetime. PMID- 20355805 TI - Interfacial width in polymer bilayer films prepared by double-spin-coating and flotation methods. AB - A spin-coating method with the aid of selective solvents has been used to construct multilayer structures for organic devices under the assumption that the solvents do not invade a preformed structure. To confirm the assumption, we examined the interfacial width (lambda(i)) of model polymer bilayers, composed of polystyrene and perdeuterated poly(methyl methacrylate), prepared by spin-coating and flotation methods. Neutron reflectivity measurements revealed that the lambda(i) value was larger for the spin-coating method than for the flotation method. These results cast doubt on the validity of the assumption. This knowledge should be kept in mind when this method is applied to construct multilayer structures. PMID- 20355807 TI - Bilayer ambipolar organic thin-film transistors and inverters prepared by the contact-film-transfer method. AB - Ambipolar organic thin-film transistors with a bilayer structure of poly(3 hexylthiophene) and [6,6]phenyl C(61) butyric acid methyl ester were fabricated using a simple solution-based, contact-film-transfer method. The transistors exhibited balanced electron and hole mobilities of 2.1 x 10(-2) and 1.1 x 10(-2) cm(2) V(-1) s(-1), respectively. Complementary inverters based on two identical ambipolar transistors showed good performance with a gain of 14. PMID- 20355806 TI - Enhanced catalytic activity of gold nanoparticles doped in a mesoporous organic gel based on polymeric phloroglucinol carboxylic acid-formaldehyde. AB - Gold nanoparticles were supported by a phloroglucinolcarboxylic acid-formaldehyde (PF) gel, a new organic gel with a 30 nm spheroid-like structure. The surface area of the PF gel with gold nanoparticles was 550 m(2)/g. Gold nanoparticles supported on a PF gel exhibited catalytic activity in the reduction of 4 nitrophenol with a reaction rate constant of 7.4 x 10(-3) s(-1), which is high in the reported heterogeneous reaction system. The adsorption behavior of 4 nitrophenol into the gel support was observed by ultraviolet-visible absorption spectroscopy. Gold nanoparticles in the PF network were characterized by scanning electron microscopy, atomic force microscopy, and transmission electron microscopy observation. The high reduction rate would be attributed to the extraction and diffusion of the reactant through the pores of a PF gel support to encounter the highly dispersed gold nanoparticles on the surface and inside the material. PMID- 20355808 TI - PEGylated Chromatography: Efficient Bioseparation on Silica Monoliths Grafted with Smart Biocompatible Polymers. AB - Novel oligo(ethylene glycol)-based thermoresponsive stationary phases have been studied for the separation of bioanalytes. Well-defined copolymers of (2 methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate were synthesized by atom-transfer radical polymerization in the presence of an N succinimidyl-functionalized initiator. The reactive chain ends of these copolymers were then reacted with amino-functionalized silica monoliths. The formed composites were studied as chromatography materials. For instance, it was demonstrated that thermoresponsive oligo(ethylene glycol)-based stationary phases allow rapid, efficient separation of steroid and protein mixtures in pure water under isocratic high-performance liquid chromatographic elution. PMID- 20355809 TI - Facile "scratching" method with common metal objects to generate large-scale catalyst patterns used for growth of single-walled carbon nanotubes. AB - A facile "scratching" method to pattern a catalyst with commonly used metal objects, such as blade, pen cover, tweezers, watchband, knife, key, clamp, and coin, was developed. The single-walled carbon nanotube (SWCNT) networks and well aligned SWCNT arrays successfully grew by chemical vapor deposition on the scratched catalyst patterns on Si/SiO(x) and quartz, respectively. This method provides an extremely simple and nearly zero-cost way to fabricate large-scale catalyst patterns used for controlled growth of SWCNT arrays, which could have potential applications in the fabrication of CNT-based devices. PMID- 20355810 TI - Silylcarborane acrylate nanoimprint lithography resists. AB - The synthesis of a novel silylcarborane acrylate monomer is reported as well as its application as an etch-resistant component for the formulation of imprint layers for UV nanoimprint lithography (NIL). By introduction of 10% by weight of the silylcarborane acrylate monomer into NIL resist formulations, the oxygen plasma etch rate of the resulting film was reduced by nearly a factor of 2. When used in NIL, the patterned resist layer had excellent oxygen plasma etch resistance, leading to effective image transfer to the underlying poly(hydroxyethyl methacrylate) lift-off layer. The latter allowed for the fabrication of metallic interdigitated electrode patterns via a NIL/lift-off process. This work demonstrates the robustness of silylcarborane-containing resists and paves the way for the investigation of new, high-resolution patterning methods. PMID- 20355811 TI - Magnetoresistance and microstructure of magnetite nanocrystals dispersed in indium-tin oxide thin films. AB - Epitaxial indium-tin oxide (ITO) thin films were fabricated on a yttria stabilized zirconia (YSZ) substrate by pulsed-laser deposition using magnetite (Fe(3)O(4)) nanoparticle dispersed ITO powders as a target. Magnetoresistance of the film at a field of 1 T was 39% at 45 K, and it stayed at 3% above 225 K. The film demonstrated cooling hysteresis in the temperature dependence of direct current magnetization. Transmission electron microscopy revealed that phase separated Fe(3)O(4) nanocrystals with widths of approximately 40-150 nm and heights of approximately 10-25 nm precipitated and grew epitaxially on the substrate in the film. Both the Fe(3)O(4)(111) and ITO(001) planes were parallel to the YSZ(001) plane. The Fe(3)O(4)(11-2) and -(1-10) planes were parallel to the ITO(100) and -(010) planes, respectively, and the planes connected smoothly at the grain boundary. The contour map of the electron density for the Fe(3)O(4)(111) plane by the first-principles electronic structure computation was similar to that for the ITO(001) plane. The [111]-oriented Fe(3)O(4) nanocrystals played the role of spin aligner for charge carriers of the epitaxial ITO film. PMID- 20355812 TI - Production of VO2 M1 and M2 nanoparticles and composites and the influence of the substrate on the structural phase transition. AB - A two-step, high-purity, high-yield synthesis of nanoparticulate vanadium dioxide, which has a greater than 10-fold potential cost reduction is reported. This consists of a short reflux of V2O5 with aspartic acid, followed by calcination at 600 degrees C or above. The particles produced have a mean diameter of approximately 90 nm with phase change characteristics of transition temperature and enthalpy that compare favorably with a commercial standard. In cases where the reduction reaction has progressed too far and a mixture of vanadium(III) and -(IV) is formed, redispersion and aging of the particulate product in water preferentially oxidizes the vanadium(III) component to vanadium(IV), thus allowing a versatile route to achieving a high-purity material. The synthesis was also used to deposit high-purity phases of VO2 onto the surfaces of other particles, and significant differences in the structural phase transition behavior and even the crystal structure were found for deposited samples. The data suggest that substrate properties may affect the characteristics of the structural phase transition, and this has significant implications for measurements on, and applications of, deposited VO2 layers and films. PMID- 20355813 TI - Solid-state reduction of silver nitrate with polyaniline base leading to conducting materials. AB - The polyaniline (PANI) base was ball-milled with silver nitrate in the solid state. Samples were prepared at various mole ratios of silver nitrate to PANI constitutional units ranging from 0 to 1.5 for three processing times, 0, 5, and 10 min. The emeraldine form of PANI was oxidized to pernigraniline, and the silver nitrate was reduced to metallic silver. Nitric acid is a byproduct, which may protonate the residual emeraldine and pernigraniline. The changes occurring in the structure of PANI are discussed on the basis of Fourier transform IR and Raman spectroscopies. Raman spectra revealed the formation of pernigraniline salt. The reaction between the two nonconducting components, emeraldine base and silver nitrate, produced a mixture of two conducting components, emeraldine or pernigraniline nitrate and metallic silver. The accompanying conductivity changes were determined. The increase in the conductivity of the original base, 10(-9) S cm(-1), up to 10(-2) S cm(-1) was found to depend on the mole ratio of silver nitrate to PANI base and on the processing time of the components in the ball mill. PMID- 20355814 TI - Probing nanodispersions of clays for reactive foaming. AB - Nanodispersions of clays in polyurethane components have been prepared. Nanoclays (both natural and organically modified) of various aspect ratios are used. The fillers are dispersed separately in polyurethane components, viz., polyol and polyisocyanate. The nanodispersions are characterized by the combined use of solution rheology, X-ray scattering, cryo-electron microscopy, and IR spectroscopy. Reactive foaming of these nanodispersions is carried out to make polyurethane nanocomposite foams. The status of the dispersion of fillers in components and in foams has been compared to investigate the effect of the foaming process in exfoliation. Interpretation of the results from different characterization techniques describes the state of the dispersion of fillers in components and in foam. The rheological and physicochemical behaviors of nanodispersions are shown to have a significant influence on the properties of nanocomposite foams. PMID- 20355815 TI - Carburization of tungsten filaments in a hot-wire chemical vapor deposition process using 1,1,3,3-tetramethyl-1,3-disilacyclobutane. AB - The alloying of tungsten filament when using 1,1,3,3-tetramethyl-1,3 disilacyclobutane (TMDSCB) in a hot-wire chemical vapor deposition reactor was systematically studied by scanning electron microscopy, Auger electron spectroscopy, analysis of the power consumed by the filament, and in situ mass spectrometric measurements of the gas-phase species produced in the process. Only carburization of the W filament was observed. The carburization is mainly caused by the interaction of methyl radicals with the filament. Graphite as well as both WC and W2C alloys can form on the filament surface, depending on the filament temperatures and source gas pressures. Both WC and graphite are converted to W2C with the diffusion of C into the filament. It is shown that filament carburization affects the consumption rate of the source gas and the intensities of gas-phase reaction products. Gas-phase reactions dominate at T < or = 1400 degrees C. The carburization rate increases with increasing filament temperatures and dominates at T > or = 1800 degrees C. PMID- 20355816 TI - Patterned growth and field-emission properties of AlN nanocones. AB - Patterned growth of AlN nanocones on a Ni-coated Si substrate is demonstrated through the reaction between AlCl(3) and NH(3) at 700 degrees C with Mo grid as a mask. The AlN nanocones are selectively deposited in the hollow region of the mask with diameters of approximately 10 nm at the tips and 50-60 nm at the roots. The field-emission (FE) performance is effectively enhanced by the patterned growth mainly because of the decreased screening effect, and both turn-on and threshold fields are dramatically decreased, less than half of the corresponding ones for the unpatterned product with similar sizes. The results indicate that patterned growth is an efficient and reproducible way to enhance the FE performance of AlN nanocones, which could be applied to optimize the FE properties of other nanoscale field emitters. PMID- 20355817 TI - Three-dimensional morphology control during wet chemical synthesis of porous chromium oxide spheres. AB - Controlling the morphological evolution in nanostructures is essential for improving their functionality, for example, in catalysis. Here, we demonstrate, using chromium oxide as a model system, that morphologies of functional binary oxide particles can be tailored by an efficient template-free synthetic approach. We construct a morphological "phase diagram" for chromium oxide spheres that shows the evolution of size and surface roughness as a function of the precursor and urea concentrations. It is notable that these chromium oxide spheres show an exceptional ability to remove azo-dye pollutant in water treatment. Thus, the porous chromium oxide spheres with very good dye absorptions are expected to be useful in alternative absorption technologies. PMID- 20355818 TI - Adsorption and lubricating properties of poly(l-lysine)-graft-poly(ethylene glycol) on human-hair surfaces. AB - We have characterized the adsorption and lubricating properties of the polycation PEG graft copolymer poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) on human-hair surfaces by means of X-ray photoelectron spectroscopy (XPS), fluorescence microscopy, and atomic force microscopy (AFM). XPS measurements indicated that PLL-g-PEG copolymers spontaneously adsorbed onto the surface of bleached-hair samples (a good model of a weathered, damaged hair surface for cosmetic care applications) from an aqueous solution. Further treatment with cationic surfactants present in common shampoo formulations removed the adsorbed PLL-g-PEG from the hair samples. Fluorescence microscopy showed that the adsorption of PLL-g-PEG onto the hair samples from an aqueous polymer solution occurred inhomogeneously. Nanotribological studies with AFM (friction vs load plots) revealed that the relationship between load and friction was approximately linear for all hair samples, while the slopes of the plots varied considerably along the hair sample surface. Under ambient, "dry" conditions, the frictional properties of the bleached, bleached + PLL-g-PEG-treated, and bleached + PLL-g PEG-treated and subsequently surfactant-treated hair samples did not reveal a clear difference. In distilled water, however, the bleached + PLL-g-PEG-treated hair samples showed statistically lower frictional properties than simply bleached or bleached + PLL-g-PEG-treated and subsequently surfactant-treated hair samples. Overall, the three instrumental techniques have consistently shown that the adsorption of PLL-g-PEG onto the hair sample surface occurs unevenly, which can be ascribed to the intrinsically heterogeneous properties of the human-hair surface. A control experiment, involving an injection of concentrated PLL-g-PEG solution into a liquid cell where an AFM tip was already scanning over a specific area (line scan mode), revealed an immediate and apparent reduction in the frictional force. Despite the inhomogeneity of the hair surface, the adsorption of the polymer seems to be extremely effective in promoting lubrication of the fiber. This suggests that the adsorbed graft copolymers act as a boundary lubricant on the hair surface. The presence of a more organized, brushlike layer of polymers contrasts with the usual random adsorption of chains that is believed to be present in the case of linear polyelectrolytes that are nowadays applied for shampoos and conditioners in the cosmetic or textile industries. PMID- 20355819 TI - New insights into proton surface mobility processes in PEMFC catalysts using isotopic exchange methods. AB - The surface chemistry and the adsorption/desorption/exchange behavior of a proton exchange membrane fuel cell catalyst are analyzed as a case study for the development of tailor-made support materials of enhanced performance and stability. By using H2, D2, and CO as probe molecules, the relevance of some surface functional groups of the catalyst support on several diffusion processes taking place during the adsorption is shown. Sulfonic groups associated with the vulcanized carbon black surface have been detected by means of spectroscopic techniques (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) and by analysis of the desorbed products during temperature programmed desorption tests by mass spectrometry. Such hydrophilic species have been observed to favor proton surface mobility and exchange with Pt-adsorbed deuterium even in the presence of adsorbed CO. This behavior is relevant both for the proper characterization of these kinds of catalysts using adsorption probes and for the design of new surface-modified carbon supports, enabling alternative proton-transfer pathways throughout the catalytic layers toward the membrane. PMID- 20355820 TI - Electrospinning of poly(alkoxyphenylenevinylene) and methanofullerene nanofiber blends. AB - Poly(p-phenylenevinylene) (PPV) derivatives have long been studied because of their attractive opto- and electroluminescent properties and have potential applications for devices such as light-emitting diodes and photovoltaics. The ability to induce alignment of these PPV derivatives may lead to the enhancement of charge mobility and their efficiency. In this study, uniform nanofibers of poly[2,5-(2'-ethylhexyloxy)]-1,4-phenylenevinylene (BEH-PPV) have been fabricated through the method of electrospinning, and an induced alignment of the polymer fibers was observed through photoluminescence data. This study also focuses on the doping of these fibers with the fullerene derivative, 1-(3-methoxycarbonyl) propyl-1-phenyl-(6,6)-C(61) (PCBM), to induce more incidence of donor/acceptor junctions. Composite fibers with up to a 1:2 weight ratio of PCBM/BEH-PPV have been fabricated and exhibited an ability to quench the photoluminescence of BEH PPV, indicative of charge transfer. PMID- 20355822 TI - Non-volatile memory devices based on polystyrene derivatives with electron donating oligofluorene pendent moieties. AB - We report bistable non-volatile memory devices based on polystyrene derivatives containing pendent electron-donating mono-, di-, and tri(9,9-dihexylfluorene), which are denoted as poly(St-Fl), poly(St-Fl(2)), and poly(St-Fl(3)), respectively. The effects of the oligofluorene chain lengths and polymer surface structures on the memory characteristics were explored. Poly(St-Fl)-, poly(St Fl(2))-, and poly(St-Fl(3))-based devices exhibited a flash memory characteristic with different turn-on threshold voltages of 2.8, 2.0, and 1.8 V, respectively, which was on the reverse trend with the highest occupied molecular orbital levels of -5.86, -5.80, and -5.77 eV. Moreover, the memory device showed a high ON/OFF current ratio of 2.5 x 10(4) and a long retention time of 10(4) s. The possible mechanism of the switching behavior was explained by the space-charge-limited current theory and filamentary conduction. The larger aggregation domain size of the polymer thin film processed from the mixed solvent of chlorobenzene/N,N dimethylformamide probably promoted the diffusion of the Al atoms into the polymer film and formed the conduction channel. Thus, it significantly reduced the turn-on threshold voltage on the studied polymer memory devices. The present study suggested that the polymer memory characteristics could be efficiently tuned through the pendent conjugated chain length and surface structures. PMID- 20355821 TI - Adhesion forces controlled by chemical self-assembly and pH: application to robotic microhandling. AB - Robotic microhandling is a promising way to assemble microcomponents in order to manufacture a new generation of hybrid microelectromechanical systems. However, at the scale of several micrometers, the adhesion phenomenon highly perturbs the micro-object release and positioning. This phenomenon is directly linked to both the object and the gripper surface chemical composition. We propose to control the adhesion by using a chemical self-assembled monolayer on both surfaces. Different types of chemical functionalization have been tested, and this paper focuses on the presentation of aminosilane-grafted 3 (ethoxydimethylsilyl)propylamine and (3-aminopropyl)triethoxysilane. We show that the liquid pH can be used to modify the adhesion and to switch from an attractive behavior to a repulsive behavior. The pH control can thus be used to increase the adhesion during handling and cancel the adhesion during release. Experiments have shown that the pH control is able to control the release of a micro-object. This paper shows the relevance of a new type of reliable submerged robotic microhandling principle, which is based on adjustment of the chemical properties of the liquid. PMID- 20355823 TI - Study of transfection efficiencies of cationic glyconanoparticles of different sizes in human cell line. AB - The growing attention toward the synthesis and uses of gold nanoparticles for biomedical applications is based on their biocompatibility, ease of functionalization, and unique optical and electronic properties. Recently, the gold nanoparticles are also found to induce the size-dependent interactions with living tissues. It has been found that gold nanoparticles of different sizes are uptaken by the cells in vitro and by the organs of living specimens in vivo at different rates. Herein, we report the use of gold nanoparticles of different sizes as a gene delivery agent. The gold nanoparticles of 10, 40, and 100 nm diameter were surface functionalized with cationic glycopolymer, and their biocompatibility under physiological conditions was investigated. The stable nanoparticles were then complexed with enhanced cyanine fluorescence protein plasmid (pECFP) and their transfection efficiencies in Hela cell line were studied. It was found that gold nanoparticles of 40 nm core diameter exhibit highest transfection efficiencies compared to the other sizes of nanoparticles studied. PMID- 20355824 TI - Biocompatible interface films deposited within porous polymers by Atomic Layer Deposition (ALD). AB - Ultrathin ceramic films were deposited throughout highly porous poly(styrene divinylbenzene) (PS-DVB) particles using a low-temperature atomic layer deposition (ALD) process. Alumina and titania films were deposited by alternating reactions of trimethylaluminum and H2O at 33 degrees C and of titanium tetrachloride and H2O2 (50 wt % in H2O) at 100 degrees C, respectively. Analytical characterization revealed that conformal alumina and titania films were grown on internal and external polymer surfaces. The improved bioactivity of the polymer substrates was revealed on the basis of the formation of hydroxyapatite (HA) in simulated body fluid. The accelerated formation of HA on the ALD-modified polymer surface was caused by the negatively charged surface provided by the ultrathin ceramic interface. The potential for ALD films to support cell attachment was demonstrated. PMID- 20355825 TI - Reinforcing poly(epsilon-caprolactone) nanofibers with cellulose nanocrystals. AB - We studied the use of cellulose nanocrystals (CNXs) obtained after acid hydrolysis of ramie cellulose fibers to reinforce poly(epsilon-caprolactone) (PCL) nanofibers. Chemical grafting with low-molecular-weight PCL diol onto the CNXs was carried out in an attempt to improve the interfacial adhesion with the fiber matrix. Grafting was confirmed via infrared spectroscopy and thermogravimetric analyses. The polymer matrix consisted of electrospun nanofibers that were collected as nonwoven webs. The morphology as well as thermal and mechanical properties of filled and unfilled nanofibers were elucidated by scanning electron microscopy, differential scanning calorimetry, and dynamic mechanical analysis, respectively. The addition of CNXs into PCL produced minimal changes in the thermal behavior of the electrospun fibers. However, a significant improvement in the mechanical properties of the nanofibers after reinforcement with unmodified CNXs was confirmed. Fiber webs from PCL reinforced with 2.5% unmodified CNXs showed ca. 1.5-fold increase in Young's modulus and the ultimate strength compared to PCL webs. Compared to the case of grafted nanocrystals, the unmodified ones imparted better morphological homogeneity to the nanofibrillar structure. The grafted nanocrystals had a negative effect on the morphology of nonwoven webs in which individual nanofibers became annealed during the electrospinning process and, therefore, could not be compared to neat PCL nonwoven webs. A rationalization for the different effects of grafted and unmodified CNXs in reinforcing PCL nanofibers is provided. PMID- 20355826 TI - Reversible switching between hydrophilic and hydrophobic superparamagnetic iron oxide microspheres via one-step supramolecular dynamic dendronization: exploration of dynamic wettability. AB - We describe the use of hydrophobic poly(aryl ether) dendrons to peripherally functionalize hydrophilic amine-containing superparamagnetic iron oxide microspheres (SPIO-NH2) in one step via imine formation. The reversible formation of imine bonds in the absence/presence of water renders dynamic control of the hydrophilicity and hydrophobicity of the microspheres (SPIO-Gn). The dynamic nature of the imine-containing dendronized microspheres (SPIO-Gn) can be "fixed" by locking the reversible 2,6-diiminopyridyl moieties with metal cations (Zn2+, Co2+, and Ni2+) to afford kinetically stable dendronized microspheres (SPIO-Gn M). Isolation of these microspheres is facilitated by convenient magnetic separation by an externally applied magnetic field. Characterization of these novel organic-inorganic hybrid microspheres has been performed by various techniques using UV/visible absorption and Fourier transform infrared spectroscopies, transmission electron microscopy, thermogravimetric analysis, and a vibrating sample magnetometer. We have demonstrated the stability and reversible switching of hydrophilicity/hydrophobicity by contact-angle measurements. In particular, the hydrophilic SPIO-NH2 microspheres demonstrated a contact angle of 42 +/- 2 degrees when a drop of water was added to a SPIO-NH2 coated mica surface. On the other hand, the hydrophobic SPIO-Gn-M dendronized microspheres demonstrated a contact angle of 85 +/- 2 degrees , an observation that involves an increase of the contact angle of over 40 degrees . Furthermore, when a drop of water was placed on a dynamic SPIO-Gn-coated mica surface, the contact angle of the water droplet decreased in time. Comparatively, the rate of decrease of the contact angle is H2O > 1% Co(OAc)2/H2O > N,N' dimethylformamide/H2O (1:1). PMID- 20355827 TI - Development of a directly patterned low-surface-energy polymer brush in supercritical carbon dioxide. AB - Carbon dioxide (CO2) is a sustainable solvent because it is nonflammable, exhibits a relatively low toxicity, and is naturally abundant. As a selective, nonpolar solvent, supercritical CO2 (scCO2) is an ideal fit for the development of low-surface-energy polymers. The development of directly patterned poly(2,2,2 trifluoroethyl methacrylate) (PTFEMA) brushes in scCO2 was investigated. PTFEMA, in particular, was selected over other fluorinated polymers because of its very high electron-beam (e-beam) sensitivity. PTFEMA brushes were grown on silicon substrates via controlled surface-initiated atom-transfer radical polymerization of TFEMA. Surface analysis techniques including ellipsometry, contact-angle goniometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy were used to characterize the thickness, hydrophilicity, roughness, and chemical composition of the polymer brushes. PTFEMA brushes were directly patterned in a single step using e-beam lithography and were processed in an environmentally benign scCO2 solvent. Tapping-mode AFM imaging confirmed the successful e-beam patterning and development of these brushes. The sensitivity of PTFEMA brushes toward direct patterning with the e-beam, followed by scCO2 development, was studied and compared to development in tetrahydrofuran solvent. Using this direct patterning method, followed by dry development in scCO2, highly resolved nanostructured polymer brush lines down to 78 nm could be prepared. This method can be generalized to prepare fluorinated low-surface-energy polymer brush surfaces in a single step for various applications. PMID- 20355828 TI - Controlled sparse and percolating cross-linking in waterborne soft adhesives. AB - The effect of low levels of cross-linking on the adhesive and mechanical properties of waterborne pressure-sensitive adhesives was investigated. We have taken advantage of a core-shell latex particle morphology obtained by emulsion polymerization to create a heterogeneous structure of cross-links without major modification of the monomer composition. The latex particles comprise a shell containing cross-linkable diacetone acrylamide (DAAM) repeat units localized on the periphery of a slightly softer core copolymer of very similar composition. Adipic acid dihydrazide was added to the latex prior to film formation to react with DAAM repeat units and affect interfacial cross-linking between particles in the adhesive films. The honeycomb-like structure obtained after drying of the latex results in a good balance between the dissipative properties required for adhesion and the resistance to creep. The characterization of the mechanical properties of the films shows that the chosen cross-linking method creates a percolating lightly cross-linked network, swollen with a nearly un-cross-linked component. With this cross-linking method, the linear viscoelastic properties of the soft films are nearly unaffected by the cross-linking while the nonlinear tensile properties are greatly modified. As a result, the long-term shear resistance of the adhesive film improves very significantly while the peel force remains nearly the same. A simple rheological model is used to interpret qualitatively the changes in the material parameters induced by cross-linking. PMID- 20355829 TI - Enhanced conversion efficiency in dye-sensitized solar cells based on hydrothermally synthesized TiO2-MWCNT nanocomposites. AB - A 50% enhancement in the conversion efficiency (4.9-7.37%) is realized in dye sensitized solar cells using hydrothermally synthesized TiO(2)-multiwalled carbon nanotube (MWCNT) nanocomposites as compared to hydrothermally synthesized TiO(2) without MWCNT and Degussa P25. Several characterizations have been employed to reveal the nature of the modification imparted to the MWCNTs under hydrothermal processing conditions and the resulting TiO(2)-MWCNT conjugation through -COOH groups. Efficient charge transfer in the nanocomposite and efficient electron transport by MWCNT (significantly higher incident-photon-to-current conversion efficiency) are suggested to be the possible reasons for the enhancement. PMID- 20355830 TI - Acidification and assembly of porphyrin at an interface: counterion matching, selectivity, and supramolecular chirality. AB - The interfacial diprotonation and assemblies of a free-base achiral porphyrin, 5,10,15,20-tetrakis(3,5-dimethoxyphenyl)-21H,23H-porphine, on various acidic subphases were investigated. It has been shown that the compound could be diprotonated in situ on an acidic subphase and can form assemblies. The interfacially organized supramolecular assemblies were transferred onto a solid substrate, and the assemblies showed supramolecular chirality. Interestingly, the supramolecular chirality of the assemblies of the diprotonated species showed a counterion-dependent behavior. For the assemblies fabricated from the aqueous HCl subphases, a strong Cotton effect (CE) could be observed, although the porphyrin itself is achiral. When an aqueous HBr solution was used as the subphase, the assemblies showed a weak CE, whereas no CE could be detected for the assemblies formulated from the HNO3 or HI subphase. Interestingly, when a mixture of HBr and NaCl, or HNO3 and NaCl, was employed as the subphase, the formed assemblies displayed chiral features similar to those fabricated on the HCl subphase, suggesting that the Cl(-) could be preferentially visualized in terms of supramolecular chirality, although the system itself is composed of achiral species. On the basis of the experimental facts and a theoretical calculation, an explanation with regard to the different sizes of the counterions and the distinct binding affinities of the counteranions to the diprotonated porphyrin species has been proposed. Our findings provide new insights into the assembly of the diprotonated porphyrins as well as the interfacially occurring symmetry breaking. PMID- 20355831 TI - Disruption and activation of blood platelets in contact with an antimicrobial composite coating consisting of a pyridinium polymer and AgBr nanoparticles. AB - Composite materials made up from a pyridinium polymer matrix and silver bromide nanoparticles embedded therein feature excellent antimicrobial properties. Most probably, the antimicrobial activity is related to the membrane-disrupting effect of both the polymer matrix and Ag(+) ions; both may work synergistically. One of the most important applications of antimicrobial materials would be their use as surface coatings for percutaneous (skin-penetrating) catheters, such as central venous catheters (CVCs). These are commonly used in critical care, and serious complications due to bacterial infection occur frequently. This study aimed at examining the possible effects of a highly antimicrobial pyridinium polymer/AgBr composite on the blood coagulation system, i.e., (i) on the coagulation cascade, leading to the formation of thrombin and a fibrin cross-linked network, and (ii) on blood platelets. Evidently, pyridinium/AgBr composites could not qualify as coatings for CVCs if they trigger blood coagulation. Using a highly antimicrobial composite of poly(4-vinylpyridine)-co-poly(4-vinyl-N-hexylpyridinium bromide) (NPVP) and AgBr nanoparticles as a thin adherent surface coating on Tygon elastomer tubes, it was found that contacting blood platelets rapidly acquire a highly activated state, after which they become substantially disrupted. This implies that NPVP/AgBr is by no means blood-compatible. This disqualifies the material for use as a CVC coating. This information, combined with earlier findings on the hemolytic effects (i.e., disruption of contacting red blood cells) of similar materials, implies that this class of antimicrobial materials affects not only bacteria but also mammalian cells. This would render them more useful outside the biomedical field. PMID- 20355832 TI - Low-melting ionic solids: versatile materials for ion-sensing devices. AB - Ionic liquids that melt slightly above room temperature (and may be called low melting ionic solids, LMISs) were used as sensing materials for the detection of ions in aqueous solutions. A simple procedure based on the consecutive melting and further solidification of the LMISs was applied to prepare solid-contact ion sensitive electrodes. A potentiometric response toward a number of anions was observed, and the possibility of altering the selectivity by incorporating additional ionophores into the LMIS matrix was demonstrated. PMID- 20355833 TI - Janus nanostructures based on Au-TiO2 heterodimers and their photocatalytic activity in the oxidation of methanol. AB - Au-TiO2 snowman-like heterodimer nanoparticles were prepared by a surface sol-gel process based on gold Janus nanoparticles whose surface-protecting monolayers consisted of a hemisphere of hydrophobic 1-hexanethiolates and the other of hydrophilic 2-(2-mercaptoethoxy)ethanol. Transmission electron microscopic measurements showed that the resulting TiO2 nanoparticles (diameter 6 nm) exhibited well-defined lattice fringes that were consistent with the (101) diffraction planes of anatase TiO2. The heterodimer nanoparticles displayed apparent photoluminescence that was ascribed to electronic transitions involving trap states of TiO2 particles, and the photocatalytic activity was manifested by the oxidative conversion of methanol into formaldehyde, which was detected quantitatively by the Nash method. The enhanced photocatalytic performance, as compared to that of the TiO2 nanoparticles alone, was ascribed to the charge separation of photogenerated electrons and holes at the Au-TiO2 interface that was facilitated by the close proximity of the gold nanoparticles. These results suggested that (i) there were at least two possible pathways for photogenerated electrons at the TiO2 conduction band, decay to the trap states and transfer to the gold nanoparticles, and (ii) energy/electron transfer from the trap states to gold nanoparticles was less efficient. In essence, this study showed that the snowman-like heterodimers might be exploited as a homogeneous photocatalytic system for the preparation of functional molecules and materials. PMID- 20355834 TI - Effect of surface capping with poly(vinyl alcohol) on the photocarrier relaxation of ZnO nanowires. AB - The effect of surface capping with poly(vinyl alcohol) (PVA) on the photocarrier relaxation of the aqueous chemically grown ZnO nanowires (NWs) has been investigated. The decay in the photocurrent during steady ultraviolet illumination due to the photocarrier relaxation has been reduced in the capped NWs, as evidenced from a decrease in the photocurrent only by 12% of its maximum value under steady illumination for 15 min and a decrease in the photocurrent by 49% of its maximum value during the same interval of time in the as-grown NWs. The surface modification is confirmed from the FESEM, HRTEM, and FTIR results. The photoluminescence spectrum shows an enhanced ultraviolet emission and a reduced defect-related emission in the capped ZnO NWs compared to bare ZnO. PMID- 20355835 TI - Diazapentacene derivatives as thin-film transistor materials: morphology control in realizing high-field-effect mobility. AB - 5,7,12,14-Tetrachloro-6,13-diaza-6,13-dihydropentacene (TCDAHP) and 5,7,12,14 tetrachloro-6,13-diazapentacene (TCDAP) were synthesized and assessed as the active channel materials for thin-film transistor applications. Analyses of the crystal structures of these molecules revealed that both exhibited slipped pi-pi stacking of the long and fused aromatic moiety. Although the packing features of the two compounds are basically identical, their highest occupied molecular orbitals, which are relevant to hole transport, are very different. Better mobility was predicted for TCDAHP over TCDAP based on the dimeric structure in the X-ray coordinates. The morphologies of thin films of TCDAHP and TCDAP prepared by thermal evaporation depend critically on the substrate on which the molecules were deposited: from the amorphous state on a SiO(2)/Si surface to the crystalline state on a pentacene buffer layer surface. The performance of thin film transistors prepared on various substrate surfaces was studied. While no field-effect mobility was observed for these films deposited on SiO(2)/Si, a high mobility of 1.4 cm(2)/(V s) for the TCDAHP film was achieved when deposited on a pentacene buffer layer prepared on a rubbed monolayer of n-nonyltrichlorosilane on a SiO(2)/Si surface. A similar device prepared from TCDAP gave a mobility of 0.13 cm(2)/(V s). PMID- 20355836 TI - Transferrable superhydrophobic surface constructed by a hexagonal CuI powder without modification by low-free-energy materials. AB - A new route combining a facile wet-chemical process and spin coating was developed to fabricate a CuI film assembled by hexagonal crystals. Remarkably, such a CuI film displays excellent superhydrophobicity without further modification by low-free-energy materials (thiol or fluoroalkylsilane). The special wettability is attributed to a hierarchical morphology of CuI crystals with two length-scale roughnesses and the nature of the material itself. Importantly, this superhydrophobicity is quite stable and the water contact angle of the as-prepared sample only decreases slightly, even when it is kept in air for about half a year. The superhydrophobicity of the as-prepared CuI powder is a bulk property of the material and not just of its surface, so such a powder coating could then prove useful in conferring superhydrophobicity to other surfaces to which it is applied. These facts might improve its practical application with environmental friendship in superhydrophobic coatings. PMID- 20355837 TI - Preparation of superhydrophobic coatings on zinc, silicon, and steel by a solution-immersion technique. AB - Zinc, silicon, and steel superhydrophobic surfaces were prepared by a simple solution-immersion technique. In the case of zinc, the method consists of dipping of the substrate in a prehydrolyzed methanol solution of 1H,1H,2H,2H (perfluorooctyl)trichlorosilane [CF(3)(CF(2))(5)(CH(2))(2)SiCl(3), PFTS] for 24 h at 50 degrees C. Micron-sized spheres (1.7-2 microm in diameter) were formed on the zinc substrate at 50 degrees C, while a featureless coating was obtained when the solution-immersion process was conducted at room temperature. When the reaction was performed at room temperature, the formation of superhydrophobic coatings took several days (up to 5 days). In contrast, immersion of silicon or steel substrates in the PFTS/methanol solution led to the formation of hydrophobic interfaces even for a prolonged immersion period at 50 degrees C. The formation of superhydrophobic surfaces on silicon and steel surfaces was only possible if a zinc foil was added in the PFTS/methanol solution containing the silicon or steel substrate. X-ray photoelectron spectroscopy analysis was used to characterize the resulting surfaces and to underline a plausible reaction mechanism. PMID- 20355838 TI - Nanofiber alignment on a flexible substrate: hierarchical order from macro to nano. AB - A simplified approach to constructing a composite material comprised of aligned electrospun nanofibers onto a flexible substrate consisting of a microfilament yarn is presented. The metal-coated knit patterns of the microfilament yarn play the role of the parallel electrode, required for the alignment of electrospun nanofibers. Hybrid materials with knitted textile as a support material and aligned high-surface-area nanofibers could represent ideal materials for use in the filtration, optical, and biomedical industries. PMID- 20355839 TI - Adhesion dynamics for cellulose nanocomposites. AB - The efficiency of poly(epsilon-caprolactone) (PCL) as a matrix polymer for cellulose nanocomposites has been investigated at the macromolecular contact level using atomic force microscopy in a colloidal probe configuration. Model cellulose microspheres grafted with PCL were prepared via ring-opening polymerization. Force measurements between the functionalized particles revealed the adhesion to be highly dependent on the contact time because of a diffusion controlled mechanism. Moreover, an increase of the temperature to 60 degrees C (close to T(m) for the PCL graft) greatly enhanced the adhesion at the polymer polymer interface, demonstrating the importance of entanglements in the annealing of composite materials. PMID- 20355840 TI - Direct production of carbon nanotubes/metal nanoparticles hybrids from a redox reaction between metal ions and reduced carbon nanotubes. AB - A method to decorate single-walled and multiwalled carbon nanotubes (CNTs) with metal nanoparticles (NPs) based on the formation of a CNT polyelectrolyte is reported. Such a method does not rely on CNT surface functionalization or the use of surfactants. It has been tested for gold (Au) and palladium (Pd). The resulting hybrids present metal NPs highly dispersed along the tube walls and with small size dispersion. The average diameters of the Au and Pd NPs were approximately 5 and approximately 3 nm, respectively. This method paves the way for large-scale decoration of CNTs with metal NPs. PMID- 20355841 TI - Characterization of inverted-type organic solar cells with a ZnO layer as the electron collection electrode by ac impedance spectroscopy. AB - An inverted-type organic bulk-heterojunction solar cell inserting zinc oxide (ZnO) as an electron collection electrode, fluorine-doped tin oxide (FTO)/ZnO/[6,6]-phenyl-C(61)-butyric acid methyl ester:regioregular poly(3 hexylthiophene) (PCBM:P3HT)/poly(3,4-ethylenedioxylenethiophene):poly(4 styrenesulfonic acid) (PEDOT:PSS)/Au, was fabricated in air and characterized by an alternating current impedance spectroscopy (IS). In the IS measurement, we observed reproducibly the electric resistance and capacitance components originating from ZnO and organic active layers, and we found that the depletion layer functioning to take out the photocurrent to the external circuit was formed in both the ZnO and PCBM:P3HT layers at the ZnO/PCBM:P3HT interface. In this letter, we propose that this IS measurement is effective for evaluating the electric properties of several layers with capacitance components in organic thin film solar cells. PMID- 20355842 TI - TiO2 film/Cu2O microgrid heterojunction with photocatalytic activity under solar light irradiation. AB - Coupling a narrow-band-gap semiconductor with TiO(2) is an effective method to produce photocatalysts that work under UV-vis light irradiation. Usually photocatalytic coupled-semiconductors exist mainly as powders, and photocatalytic activity is only favored when a small loading amount of narrow-band-gap semiconductor is used. Here we propose a heavy-loading photocatalyst configuration in which 51% of the surface of the TiO(2) film is covered by a Cu(2)O microgrid. The coupled system shows higher photocatalytic activity under solar light irradiation than TiO(2) and Cu(2)O films. This improved performance is due to the efficient charge transfer between the two phases and the similar opportunity each has to be exposed to irradiation and adsorbates. PMID- 20355843 TI - Electrochemical control of the conductivity in an organic memristor: a time resolved X-ray fluorescence study of ionic drift as a function of the applied voltage. AB - Grazing-incidence X-ray fluorescence measurements were applied for a time resolved study of an organic memristor conductivity variation mechanism. A comparison of these results with electrical measurements has allowed us to conclude that the variation of the fluorescence intensity of Rb ions is directly connected to the ionic charge transferred between the conducting polymer and the solid electrolyte, which made up the device. In addition, the conductivity of the memristor was shown to be a function of the transferred ionic charge. PMID- 20355844 TI - A nanoscale metal alkoxide/oxide adhesion layer enables spatially controlled metallization of polymer surfaces. AB - Seeding polymer substrates for the attachment and growth of metallic contacts is an important problem in modern microcircuit fabrication. A new method to effect such polymer metallization is described in which the polymer is first treated with vapor of zirconium or titanium tetra-tert-butoxide and then thermalyzed to give several monolayers of zirconium or titanium oxides that are attached to the polymer surfaces. The thickness of this layer can be controlled by the vapor exposure time. The thin oxide layers withstand removal by strenuous flexing of the polymers, and they absorb copper sulfate from an aqueous solution. Upon simple treatment with dialkylaminoborane or sodium borohydride, the polymer is metallized with copper. The tetra-tert-butoxides can be deposited through a mask, and patterned metallization of the polymers is easily accomplished. PMID- 20355845 TI - Effect of hydrogen bonding on the compressive strength of dihydroxypoly(p phenylenebenzobisoxazole) fibers. AB - By the introduction of binary hydroxyl groups into poly(p-phenylenebenzoxazole) (PBO) macromolecular chains, a series of dihydroxypoly(p phenylenebenzobisoxazole) (DHPBO) chains were prepared, and the effect of the hydroxyl groups on the axial compression property of DHPBO fibers was investigated. The variable-temperature Fourier transform infrared spectrum proved the existence of hydrogen bonds in DHPBO chains. Furthermore, the axial compression bending test showed that the introduction of hydroxyl groups into macromolecular chains apparently improved the compression resistance property of DHPBO fibers. Finally, a proposed arrangement of the hydrogen bonding in DHPBO fibers is presented. PMID- 20355846 TI - Linear tricationic room-temperature ionic liquids: synthesis, physiochemical properties, and electrowetting properties. AB - Efficient and facile synthesis of novel linear tricationic room-temperature ionic liquids was performed, and their physiochemical properties were determined. Different physiochemical properties were observed according to the structural variations such as the cationic moiety and the counteranion of the ionic liquid. The electrowetting properties of these ionic liquids were also investigated, and linear tricationic ionic liquids were shown to be advantageous as effective electrowetting materials due to their high structural flexibility. PMID- 20355847 TI - Functionalization of a cotton fabric surface with titania nanosols: applications for self-cleaning and UV-protection properties. AB - In this study, cotton fabric was successfully modified by titania nanosols prepared by means of the sol-gel process with tetrabutyl orthotitanate [Ti(OC(4)H(9))(4)] as the active ingredient. The cotton fabric was padded with the nanosol solution, dried at 60 degrees C, and cured at 150 degrees C. Scanning electron microscopy showed the presence of a titania film on the fiber surface. The photocatalytic properties of titania-nanosol-treated cotton fabric were investigated. The results showed that stains of coffee and red wine were successfully decomposed by exposure of the stained fabric to UV radiation. Furthermore, titania-nanosol treatment imparted to the cotton fabric a very good protection against UV radiation. The durability of the treatment was investigated by performing repeated home laundering, and the results showed no effect of laundering on the UV-protection efficiency. PMID- 20355848 TI - Control and characterization of the structural, electrical, and optical properties of amorphous zinc-indium-tin oxide thin films. AB - Zinc-indium-tin oxide (ZITO) films are grown by pulsed-laser deposition in which 30% of the indium in the In(2)O(3) structure is replaced by substitution with zinc and tin in equal molar proportions: In(2-2x)Zn(x)Sn(x)O(3), where x = 0.3. Films grown at 25 and 100 degrees C exhibit electron diffraction patterns (EDPs) typical of amorphous materials. At a deposition temperature of 200 degrees C, evidence of crystallinity begins to appear in the EDP data and becomes more evident in films deposited at 400 degrees C. The advent of crystallinity affects the electrical properties of the ZITO film, and the effect is ascribed to the boundaries between phases in the films. The electrical and optical properties of the amorphous ZITO films grown at 25 degrees C are dependent on the oxygen partial pressure (P(O(2))) during film growth, transitioning from a high-mobility (36 cm(2)/V x s) conductor (sigma approximately 1700 S/cm) at P(O(2)) = 5 mTorr to a high-mobility semiconductor at P(O(2)) approximately 20 mTorr. Field-effect transistors (FETs) prepared with as-deposited amorphous ZITO channel layers on p(+)-Si/300 nm SiO(2) substrates yield FETs with on/off ratios of 10(6), off currents of 10(-8) A, and field-effect saturation mobilities of 10 cm(2)/V x s. PMID- 20355849 TI - Hindered water motions in hardened cement pastes investigated over broad time and length scales. AB - We investigated the dynamics of confined water in different hydrated cement pastes with minimized contributions of capillary water. It was found that the water motions are extremely reduced compared to those of bulk water. The onset of water mobility, which was modified by the local environment, was investigated with elastic temperature scans using the high-resolution neutron backscattering instrument SPHERES. Using a Cauchy-Lorenz distribution, the quasi-elastic signal observed in the spectra obtained by the backscattering spectrometer was analyzed, leading to the identification of rotational motions with relaxation times of 0.3 ns. Additionally, neutron spin echo (NSE) spectroscopy was used to measure the water diffusion over the local network of pores. The motions observed in the NSE time scale were characterized by diffusion constants ranging from 0.6 to 1.1 x 10(-9) m(2) s(-1) most likely related to water molecules removed from the interface. In summary, our results indicate that the local diffusion observed in the gel pores of hardened cement pastes is on the order of that found in deeply supercooled water. Finally, the importance of the magnetic properties of cement pastes were discussed in relation to the observation of a quasi-elastic signal on the dried sample spectra measured using the time-of-flight spectrometer. PMID- 20355850 TI - A novel reactive processing technique: using telechelic polymers to reactively compatibilize polymer blends. AB - Difunctional reactive polymers, telechelics, were used to reactively form multiblock copolymers in situ when melt-blended with a blend of polystyrene and polyisoprene. To quantify the ability of the copolymer to compatibilize the blends, the time evolution of the domain size upon annealing was analyzed by SEM. It was found that the most effective parameter to quantify the ability of the copolymer to inhibit droplet coalescence is K(rel)t(stable), the relative coarsening constant multiplied by the stabilization time. These results indicate that intermediate-molecular-weight telechelic pairs of both highly reactive Anhydride-PS-Anhydride/NH(2)-PI-NH(2) and slower reacting Epoxy-PS-Epoxy/COOH-PI COOH both effectively suppress coalescence, with the optimal molecular weight being slightly above the critical molecular weight of the homopolymer, M(c). The effects of telechelic loading were also investigated, where the optimal loading concentration for this system was 0.5 wt %, as higher concentrations exhibited a plasticizing effect due to the presence of unreacted low-molecular-weight telechelics present in the blend. A determination of the interfacial coverage of the copolymer shows that a conversion of approximately 1.5-3.0% was required for 20% surface coverage at 5.0 wt % telechelic loading, indicating a large excess of telechelics in this system. At the optimal loading level of 0.5 wt %, a conversion of 15% was required for 20% surface coverage. The results of these experiments provide a clear understanding of the role of telechelic loading and molecular weight on its ability to reactively form interfacial modifiers in phase separated polymer blends and provide guidelines for the development of similar reactive processing schemes that can use telechelic polymers to reactively compatibilize a broad range of polymer blends. PMID- 20355851 TI - Silver-coated silica beads applicable as core materials of dual-tagging sensors operating via SERS and MEF. AB - We have developed dual-tagging sensors, operating via both surface-enhanced Raman scattering (SERS) and metal-enhanced fluorescence (MEF), composed of silver coated silica beads onto which were deposited SERS markers and dye-grafted polyelectrolytes, for multiplex immunoassays. Initially, a very simple electroless-plating method was applied to prepare Ag-coated silica beads. The Raman markers were then assembled onto the Ag-coated silica beads, after which they were brought to stabilization by the layer-by-layer deposition of anionic and cationic polyelectrolytes including a dye-grafted polyelectrolyte. In the final stage, the dual-tagging sensors were assembled onto them with specific antibodies (antihuman-IgG or antirabbit-IgG) to detect target antigens (human-IgG or rabbit-IgG). The MEF signal was used as an immediate indicator of molecular recognition, while the SERS signals were subsequently used as the signature of specific molecular interactions. For this reason, these materials should find wide application, especially in the areas of biological sensing and recognition that rely heavily on optical and spectroscopic properties. PMID- 20355852 TI - Surface electric fields increase osteoblast adhesion through improved wettability on hydroxyapatite electret. AB - Osteoblasts are susceptible to the surface characteristics of bioceramics and stimulation from outside the cells. The purpose of this study was to evaluate the effects of electrical polarization on surface characteristics and osteoblastic adhesion. The surface characteristics revealed that electrical polarization had no effect on the surface roughness, crystallinity, and constituent elements. According to contact-angle measurements, electrically polarized hydroxyapatite (HA), which provides two kinds of surfaces, negatively charged HA (N-HA) and positively charged HA (P-HA), was even more hydrophilic than that of normal HA (O HA). Morphological observations and quantitative analyses revealed that the typical adhered cells had a round shape on O-HA but had a spindle or fanlike spreading configuration on N-HA and P-HA 1 h after seeding. After 3 h of cultivation, the rate of the number of spread cells and the size of the focal adhesions on O-HA increased and approached that of N-HA and P-HA. However, the cell areas positively stained for actin, which indicates the degree of cell spreading, were distinctly larger on N-HA and P-HA than that on O-HA. The number of focal adhesions per cell was also less than that on N-HA and P-HA. PMID- 20355853 TI - Innovative UVC light (185 nm) and radio-frequency-plasma pretreatment of Nylon surfaces at atmospheric pressure and their implications in photocatalytic processes. AB - Innovative pretreatment by UVC light (185 nm) and by radio-frequency (RF) plasma at atmospheric pressure to functionalize the Nylon surface, increasing its bondability toward TiO(2), is reported in this study. In the case of UVC light pretreatment in air, the molar absorption coefficient of O(2)/N(2) at 185 nm is very low and the air in the chamber absorbs very little light from the UVC source before reaching the Nylon sample. Nylon fabrics under RF plasma were also functionalized at atmospheric pressure because of the marked heating effect introduced in the Nylon by the RF plasma. This effect leads to intermolecular bond breaking and oxygenated surface groups in the topmost Nylon layers. Both pretreatments enhanced significantly the photocatalytic discoloration of the red wine stain in Nylon-TiO(2) compared with samples without pretreatment. The UVC and RF methods in the absence of vacuum imply a considerable cost reduction to functionalize textile surfaces, suggesting a potential industrial application. Red-wine-stain discoloration under simulated sunlight was monitored quantitatively by diffuse-reflectance spectroscopy and by CO(2) evolution. X-ray photoelectron spectroscopy (XPS) was used to monitor the changes of the C, N, and S species on the Nylon topmost layers during the discoloration process. Significant changes in the XPS spectra of Ti 2p peaks were observed during discoloration of the wine spots. Wine stains attenuated the signal of the Ti 2p (458.4 eV) peak in the Nylon-TiO(2)-stained wine sample at time zero (from now on, the time before the discoloration process). Furthermore, a decrease of the wine-related O 1s signal at 529.7 eV and N 1s signal at 399.5 eV was observed during the discoloration process, indicating an efficient catalytic decomposition of the wine pigment on Nylon-TiO(2). X-ray diffraction detected the formation of anatase on the Nylon fibers. High-resolution transmission electron microscopy shows the formation of anatase particles with sizes between 8 and 20 nm. PMID- 20355854 TI - Functionalized Au22 clusters: synthesis, characterization, and patterning. AB - We synthesized fluorescent, porphyrin-anchored, Au(22) clusters in a single step, starting from well-characterized Au(25) clusters protected with glutathione (-SG) by a combined core reduction/ligand exchange protocol, at a liquid-liquid interface. The prepared cluster was characterized by UV/vis, photoluminescence, X ray photoelectron spectroscopy (XPS), scanning electron microscopy, elemental analysis, and matrix-assisted laser desorption ionization mass spectrometry. The absence of a 672 nm intraband transition of Au(25) and the simultaneous emergence of new characteristic peaks at 520 and 635 nm indicate the formation of the Au(22) core. An increase in the binding energy of 0.4 eV in Au 4f core-level peaks confirmed the presence of a reduced core size. Quantitative XPS confirmed the Au/S ratio. The presence of a free base, tetraphenylporphyrin (H(2)TPPOAS-), on the Au(22) core was confirmed by fluorimetric titrations with Cu(2+) and Zn(2+) ions. From all of these, the composition of the cluster was determined to be Au(22)[(-SG)(15)(-SAOPPTH(2))(2)], which was supported by mass spectrometry and elemental analysis. We utilized the fluorescence nature of these water soluble clusters for the fabrication of fluorescent patterns by soft lithography. The patterns were studied using tapping-mode atomic force microscopy and confocal fluorescence imaging. PMID- 20355855 TI - A novel solution process for the synthesis of VO2 thin films with excellent thermochromic properties. AB - This article describes a novel and simple route to preparing VO(2) thermochromic films by using a VOCl(2) solution with poly(vinylpyrrolidone) (PVP). X-ray diffraction and Raman spectra showed that the VO(2) films deposited with PVP consisted of a nearly pure monoclinic/rutile (M/R) phase. Conversely, films prepared without PVP contained obviously impure crystalline phases. The as prepared films with PVP showed excellent optical properties compared to those prepared by common gas-phase methods: an integral visible transmittance of 54.5% and an IR reduction (change in transmittance) of 41.5% at 2000 nm. The phase transition temperatures were adjusted from 69 to 54 degrees C by tungsten doping. Equipment analyses revealed that PVP plays two roles in the film formation. First, it fundamentally acts as a film-forming promoter to improve physical gelation via interactions among oppositely charged carbonyl groups and amine groups of the polymer. Second, the negatively charged carbonyl groups can interact with VO(2+) to form a uniform mixed-gel film after solvent evaporation. Thus, the addition of PVP can stabilize the solution and improve the as-prepared film quality and phase purity. The current study suggests that the process has promise in applications of smart windows. PMID- 20355856 TI - Photosensitive polymeric materials for two-photon 3D WORM optical data storage systems. AB - We report the photochemistry and development of a fluorescence readout-based, nonlinear absorption, three-dimensional optical data storage system. In this system, writing was achieved by acid generation upon two-photon absorption (2PA) of a photoacid generator (PAG; at 710 or 730 nm). Readout was then performed by interrogating two-photon-absorbing dyes, after protonation, at 860 nm. Linear and nonlinear photophysical characterization of 2PA PAGs and acid-sensitive fluorescent dyes demonstrates good spectral resolution between the PAG and protonated 2PA dye and relatively high two-photon absorptivity. Solution spectroscopic studies confirm photoacid generation and dye protonation. Two photon recording and readout of voxels were demonstrated in five and eight consecutive, crosstalk-free layers within a polymer matrix, generating a data storage capacity of up to 1.8 x 10(13) bits/cm(3). PMID- 20355857 TI - Solution-prepared hybrid-nanoparticle dielectrics for high-performance low voltage organic thin-film transistors. AB - Oleic acid capped barium strontium titanate (OA-BST) nanoparticles were synthesized for solution-prepared dielectrics in organic thin-film transistors (OTFTs). The as-synthesized nanoparticles were well-dispersed in organic solvents to deposit very homogeneous dielectric films by direct spin coating. Bottom-gate pentacene TFTs fabricated using these nanoparticle dielectric films showed high mobilities of 1-2 cm(2) V(-1) s(-1) with on/off ratios of 10(3) under a low driven voltage of -2.5 V. Top-gate poly(3,3'''-didodecylquaterthiophene) (PQT-12) TFTs with nanoparticle dielectrics also exhibited a low-voltage operation (-5 V) performance with mobilities of 0.01-0.1 cm(2) V(-1) s(-1) and on/off ratios of 10(3)-10(4). Detailed studies on the gate voltage-dependent mobility of the devices showed that only a low gate electric field needed to achieve the saturated mobility for the OA-BST-based pentacene OTFTs could be attributed to the low trapped-state densities (<3.9 x 10(11) cm(-2)) at the dielectric/semiconductor interfaces for these devices. PMID- 20355858 TI - Toward the rational design of lipid gene vectors: shape coupling between lipoplex and anionic cellular lipids controls the phase evolution of lipoplexes and the efficiency of DNA release. AB - A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interaction with anionic cellular lipids, resulting in DNA release. At the early stages of interaction, we found a universal behavior of lipoplex/anionic lipid (AL) mixtures: the lipoplex structure is slightly perturbed, while the one-dimensional DNA lattice between cationic membranes is largely diluted by ALs. This finding is in excellent agreement with previous suggestions on the mechanism of DNA unbinding from lipoplexes by ALs. Upon further interaction, the propensity of a given lipoplex structure to be solubilized by anionic cellular lipids strongly depends on the shape coupling between lipoplex and ALs. Furthermore, we investigated the effect of the membrane charge density and a general correlation resulted: the higher the membrane charge density of anionic membranes, the higher their ability to solubilize the structure of lipoplexes and to promote DNA release. Lastly, the formation of nonlamellar phases in lipoplex/AL mixtures is regulated by the propensity of anionic cellular lipids to adopt nonlamellar phases. Remarkably, also phase transition rates and DNA release were found to be strongly affected by the shape coupling between lipoplex and ALs. It thus seems likely that the structural and phase evolution of lipoplexes may only be meaningful in the context of specific anionic cellular membranes. These results highlight the phase properties of the carrier lipid/cellular lipid mixtures as a decisive factor for optimal DNA release and suggest a potential strategy for the rational design of efficient cationic lipid carriers. PMID- 20355859 TI - Patterning lead zirconate titanate nanostructures at sub-200-nm resolution by soft confocal imprint lithography and nanotransfer molding. AB - Patterned sol-gel-derived lead zirconate titanate (PZT) thin films with lateral resolutions down to 100 nm on silicon are reported. Both an imprint and a transfer-molding method were employed. The formed patterns after annealing were characterized with scanning electron microscopy, atomic force microscopy, and X ray diffraction. Despite the small dimensions and flexibility of the poly(dimethylsiloxane) (PDMS) stamps used for patterning, the quality of replication was found to be good. The influence of the surface energies of the substrate, PDMS mold, and precursor solution on the quality of pattern replication is discussed. The colloidal structure of the PZT sol-gels from which the patterns were made was studied with small-angle X-ray scattering. The sols were found to be chemically homogeneous down to a length scale of approximately 2 nm and higher, which is sufficient for pattern replication on approximately 100 nm scale. PMID- 20355860 TI - Graphite oxide flame-retardant polymer nanocomposites. AB - Graphite oxide (GO) polymer nanocomposites were developed at 1, 5, and 10 wt % GO with polycarbonate (PC), acrylonitrile butadiene styrene, and high-impact polystyrene for the purpose of evaluating the flammability reduction and material properties of the resulting systems. The overall morphology and dispersion of GO within the polymer nanocomposites were studied by scanning electron microscopy and optical microscopy; GO was found to be well-dispersed throughout the matrix without the formation of large aggregates. Mechanical testing was performed using dynamic mechanical analysis to measure the storage modulus, which increased for all polymer systems with increased GO loading. Microscale oxygen consumption calorimetry revealed that the addition of GO reduced the total heat release and peak heat release rates in all systems, and GO-PC composites demonstrated very fast self-extinguishing times in vertical open flame tests, which are important to some regulatory fire safety applications. PMID- 20355861 TI - Characterization of sol-gel-encapsulated proteins using small-angle neutron scattering. AB - Entrapment of biomolecules in silica-derived sol-gels has grown into a vibrant area of research since it was originally demonstrated. However, accessing the consequences of entrapment on biomolecules and the gel structure remains a major challenge in characterizing these biohybrid materials. We present the first demonstration that it is possible with small-angle neutron scattering (SANS) to study the conformation of dilute proteins that are entrapped in transparent and dense sol-gels. Using deuterium-labeled green fluorescent protein (GFP) and SANS with contrast variation, we demonstrate that the scattering signatures of the sol gel and the protein can be separated. Analysis of the scattering curves of the sol-gels using a mass-fractal model shows that the size of the colloidal silica particles and the fractal dimensions of the gels were similar in the absence and presence of protein, demonstrating that GFP did not influence the reaction pathway for the formation of the gel. The major structural difference in the gels was that the pore size was increased 2-fold in the presence of the protein. At the contrast match point for silica, the scattering signal from GFP inside the gel became distinguishable over a wide q range. Simulated scattering curves representing a monomer, end-to-end dimer, and parallel dimer of the protein were calculated and compared to the experimental data. Our results show that the most likely structure of GFP is that of an end-to-end dimer. This approach can be readily applied and holds great potential for the structural characterization of complex biohybrid and other materials. PMID- 20355862 TI - Influence of the film thickness and morphology on the colorimetric properties of spray-coated electrochromic disubstituted 3,4-propylenedioxythiophene polymers. AB - Variation of the colorimetric properties as a function of the film thickness and morphology has been investigated for two spray-coated electrochromic disubstituted 3,4-propylenedioxythiophene polymers. Changes in the luminance, hue, and saturation have been tracked using CIE 1931 Lxy chromaticity coordinates, with CIELAB 1976 color space coordinates, L*, a*, and b*, being used to quantify the colors. For (precycled) neutral PProDOT-(Hx)(2) films, with an increase in the thickness, L* is seen to decrease, with a* and b* coordinates moving in positive and negative directions, respectively, with quantification of the pink/purple (magenta) color as the summation of red and blue. For all thicknesses, L* is comparable, pre- and postcycling, with a* decreasing (less red) and b* becoming more negative (more blue) and the film now appearing as purple in the neutral state. Color coordinates for the reverse (reduction) direction exhibited hysteresis in comparison with the initial oxidation, with the specific choice of perceived color values depending not only on the film thickness but also on both the potential applied and from which direction the potential is changed. Neutral PProDOT-(2-MeBu)(2) films appear blue/purple to the eye both as-deposited and after potential cycling to the transparent oxidized state. For the neutral, colored state, with an increase in the thickness, L* is seen to decrease, with a* and b* coordinates moving in positive and negative directions, respectively. For PProDOT-(2-MeBu)(2) films, the a* coordinates are lower positive values and the b* coordinates are higher negative values, thus quantifying the high dominance of the blue color in the blue/purple films compared to the pink/purple PProDOT-(Hx)(2) films. As for the PProDOT-(Hx)(2) films, the tracks of the color coordinates show that the specific choice of perceived color values depends on the film thickness. Unlike the PProDOT-(Hx)(2) films, hysteresis is absent in the oxidation/reduction track of the x-y coordinates for the PProDOT-(2-MeBu)(2) films, although slight hysteresis is present in the luminance. Characterization of the film morphologies through atomic force microscopy reveals a much rougher, higher surface area morphology for the PProDOT-(2-MeBu)(2) films versus the PProDOT-(Hx)(2) films. The branched repeat unit in the PProDOT-(2-MeBu)(2) films provides a structure that allows ions to ingress/egress more effectively, thus removing hysteresis from the optical response. PMID- 20355863 TI - Dangling chain elastomers as repeatable fibrillar adhesives. AB - This work reports on repeatable adhesive materials prepared by controlled grafting of dangling hetero chains from polymer elastomers. The dangling chain elastomer system was prepared by grafting poly(n-butyl acrylate) (PBA) chains from prefunctionalized polydimethylsiloxane (PDMS) elastomer networks using atom transfer radical polymerization. To study the effects of chain growth and network strain as they relate to network adhesion mechanics, various lengths of PBA chains with degree of polymerizations (DP) of 65, 281, 508, and 1200 were incorporated into the PDMS matrix. PBA chains with a DP value of 281 grafted from a flat PDMS substrate showed the highest (approximately 3.5-fold) enhancement of nano- and macroscale adhesion relative to a flat raw (ungrafted and not prefunctionalized) PDMS substrate. Moreover, to study the effect of PBA dangling chains on adhesion in fibrillar elastomer structures inspired by gecko foot hairs, a dip-transfer fabrication method was used to graft PBA chains with a DP value of 296 from the tip endings of mushroom-shaped PDMS micropillars. A PBA chain covered micropillar array showed macroscale adhesion enhancement up to approximately 7 times relative to the flat ungrafted prefunctionalized PDMS control substrate, showing additional nonoptimized approximately 2-fold adhesion enhancement due to fibrillar structuring and mushroom-shaped tip ending. These dangling hetero chains on elastomer micro-/nanofibrillar structures may provide a novel fabrication platform for multilength scale, repeatable, and high-strength fibrillar adhesives inspired by gecko foot hairs. PMID- 20355864 TI - Color purity in polymer electrochromic window devices on indium-tin oxide and single-walled carbon nanotube electrodes. AB - Dual polymer absorptive/transmissive electrochromic (EC) window devices have been assembled using the solution-processable and high-EC-contrast polymer PProDOT (CH(2)OEtHx)(2) as the EC material, along with a non-color-changing electroactive polymer, poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl methacrylate) (PTMA), as the counter electrode material. Indium-tin oxide (ITO) and highly transmissive single walled carbon nanotube (SWNT) film coated glass electrodes are used as electrode substrates. The use of the EC/non-color-changing polymer combination allowed us to construct window devices that rapidly switch between magenta and highly transmissive (>95% T for ITO and approximately 79% T for SWNT) states with large optical modulation (>71% DeltaT for ITO and 66% DeltaT for SWNT). The devices showed effective coloration and bleaching: the lightness parameter (L*) changing from 67 to 95 for ITO (approximately 50-92 for SWNT), essentially reaching a diffuse white upon oxidation. The color modulates from highly pure magenta with a* = 28 (red hue) and b* = -28 (blue chroma) for ITO (a* = 40 and b* = -36 for SWNT) to nearly colorless with a* = 1 and b* = -1 for ITO (a* = -2 and b* = -3 for SWNT) devices. Increasing the switching voltage from 2.55 V up to 3.5 V resulted in faster SWNT-based window device performance. PMID- 20355865 TI - Optical-limiting properties of oleylamine-capped gold nanoparticles for both femtosecond and nanosecond laser pulses. AB - We report strong broad-band optical-limiting properties of oleylamine-capped gold nanoparticles in solution for both femtosecond and nanosecond laser pulses. The nanosecond optical-limiting effects were characterized by using fluence-dependent transmittance measurements with 7 ns laser pulses at 532 and 1064 nm, and the femtosecond optical-limiting effects were characterized with a z-scan technique using 300 fs laser pulses at 780 nm. The oleylamine-capped gold nanoparticles were found to show strong broad-band optical-limiting effects for nanosecond laser pulses at 532 and 1064 nm and femtosecond laser pulses at 780 nm. These oleylamine-capped gold nanoparticles displayed exceptional optical-limiting effects with thresholds lower than that of carbon nanotube suspension, a benchmark optical limiter. Input-fluence- and angle-dependent scattering measurements suggested that nonlinear scattering played an important role in the observed optical-limiting behavior at 532 and 1064 nm. PMID- 20355866 TI - Synthesis and electrocatalytic activity of photoreduced platinum nanoparticles in a poly(ethylenimine) matrix. AB - Monodisperse polymer-mediated platinum (Pt) nanoparticles (NPs) have been synthesized by photoreduction in the presence of poly(ethylenimine) (PEI), a hyperbranched polymer. The formation process of the Pt NPs is pursued by UV-vis spectroscopy, and the formation mechanism is discussed. The morphology and size of the Pt NPs were characterized by transmission electron microscopy (TEM). TEM imaging shows that the Pt NPs' average diameter is 2.88 +/- 0.53 nm. The PEI/Pt NPs were immobilized on glassy carbon electrodes, and the electrocatalytic activity of the catalysts was investigated by cyclic voltammetry. PEI/Pt NPs exhibit very high catalytic activity for a methanol oxidation reaction. PEI/Pt NPs on glassy carbon electrodes are robust, showing good tolerance to poisoning even after many cycles. The electrocatalytic activity of PEI/Pt NPs compares favorably with other polymer-mediated Pt NPs. The results indicate that PEI is an appropriate complexing reducing agent for the photochemical production of Pt NPs and a good capping agent, allowing immobilization of the NPs on the working electrode. PMID- 20355867 TI - Preparation and characterization of microporous layers on titanium. AB - Microporous layers on titanium (Ti) are formed by chemical treatment in highly concentrated alkaline media, and their properties and growth mechanism are examined using electrochemical techniques, in situ resistometry, scanning electron microscopy (SEM), grazing-incident X-ray diffraction (GIXRD), and glow discharge optical emission spectroscopy (GD-OES). Chemical treatment in a 5 M aqueous KOH solution yields results superior to those from the same treatment in a 5 M aqueous NaOH solution, while a 3 M aqueous LiOH solution does not produce porous layers. The cation constituting the solution plays a vital role in the process. An SEM analysis reveals that the KOH solution is the most effective in forming microporosity and that the longer the treatment time, the more porous the near-surface layer. The results of GIXRD analysis show the presence of Na(2)Ti(5)O(11) and K(2)Ti(6)O(13) in the layers formed in the NaOH and KOH solutions, respectively; in the case of the LiOH solution, TiO(2) is formed. Chemical treatment in the NaOH and KOH solutions resembles a general corrosion process with the existence of local cathodic and anodic sites. The reduction reaction produces H(2), some of which becomes absorbed in the near-surface region of Ti, while the oxidation reaction produces the above-mentioned compounds and/or an oxide layer. The presence of hydrogen (H) within the solid is detected using GD-OES. The H-containing near-surface layer partially dissolves, yielding a microporous structure. The development and dissolution of the H-containing near surface layer of Ti upon chemical treatment in the NaOH and KOH solutions are confirmed by resistometry measurements. They point to the formation of a compact passive layer on Ti upon exposure to the LiOH solution. PMID- 20355868 TI - Three-dimensional surface patterning by DNA-modifying enzymes. AB - Self-assembled patterned multilayers may be fabricated using DNA monolayers and the orchestrated reactions of DNA-modifying enzymes. To demonstrate this approach, DNA monolayers were formed on silicon and cleaved quantitatively with a restriction enzyme. Subsequently, fluorescently labeled nucleotides were covalently incorporated to the cleaved DNA. Nucleotide addition was shown to be highly selective according to the sequence at the cleavage site, and no nonspecific adsorption to the surface was observed. The dual action of the DNA modifying enzymes was quantitative and could be utilized in the fabrication of multilayered structures. Other DNA-modifying enzymes can be exploited in this manner to enrich the repertoire of self-assembly supramolecular structure fabrication. PMID- 20355869 TI - Wettability of electrospun poly(vinylpyrrolidone)-titania fiber mats on glass and ITO substrates in aqueous media. AB - Networks of nano/microfibers (fiber mats) have been electrospun from solutions of dispersed poly(vinylpyrrolidone) (PVP) and a titania precursor onto glass and indium-tin oxide (ITO) plates to study their wettability. Collection time and electrode separation are the two key fabrication parameters investigated, along with the flow rate, polymer molecular weight, and drying conditions, to determine the effects on network morphology and the relationship to contact angles. Measurements indicate that the fiber mats on both glass and ITO increase in thickness and contact angle for longer spinning time and shorter distance, resulting in an extreme case of apparent ultrahydrophobicity on ITO of up to 169.9 degrees with water. The fiber mats are shown by optical microscopy to exhibit differences in morphology for insulating glass (straight) and conductive ITO (loopy) substrates responsible for the wide-ranging and well-controlled wettability to within 1-2 degrees. Fiber mats baked at 200 degrees C for 24 h show excellent mechanical stability with wetting even against frequent heavy rinsing, conducive for reusable aqueous applications such as biosensors or cellular scaffolding. PMID- 20355870 TI - Photopatternable source/drain electrodes using multiwalled carbon nanotube/polymer nanocomposites for organic field-effect transistors. AB - We fabricated photopatternable and conductive polymer/multiwalled carbon nanotube (MWNT) composites by dispersing MWNTs with poly(4-styrenesulfonic acid) (PSS) and poly(acrylic acid) (PAA) in water. PAA enables photo-cross-linking in the composite by adding ammonium dichromate, and PSS assists the dispersion of MWNTs in the composites, leading to higher conductivity. Composite films of PAA/PSS MWNTs were characterized by conductivities of 1.4-210 S/cm and a work function of 4.46 eV, which could be increased to 4.76 eV during UV photo-cross-linking. By using PAA/PSS-MWNT composites as source/drain electrodes, 6,13 bis(triisopropylsilylethynyl)pentacene field-effect transistors (FET) exhibited a field-effect mobility of 0.101 +/- 0.034 cm(2)/(V s), which is 9 times higher than that of FETs fabricated with gold as source/drain electrodes (0.012 +/- 0.003 cm(2)/(V s)). PMID- 20355871 TI - Polyelectrolyte/nanosilicate thin-film assemblies: influence of pH on growth, mechanical behavior, and flammability. AB - Thin composite films of branched polyethylenimine (BPEI) and Laponite clay platelets were prepared using layer-by-layer assembly. The film thickness was tailored by altering the pH of the aqueous mixtures used to deposit these films, resulting in growth that ranged from 0.5 to 5 nm/bilayer (BL). High-pH BPEI and low-pH clay produced the thickest films. The microstructure of tilted Laponite clay platelet stacks is observed with transmission electron microscopy when using unadjusted BPEI (pH 10.3) and pH 6 Laponite. This recipe resulted in a film with 83 wt % clay and a hardness of 0.5 GPa. In all films, the clay platelets are uniformly deposited and look analogous to a cobblestone path in atomic force microscopy surface images. Several 40-BL films, with thicknesses of 100 nm or more, exhibit reduced moduli ranging from 7 to 10 GPa and hardness of around 0.5 GPa, suggesting that these transparent films could be useful as hard coatings for plastic films. These thin coatings were also deposited onto cotton fabric. Each individual cotton fiber was uniformly coated, and the fabric has significantly more char left after burning than the uncoated fabric. Thermogravimetric analysis results reveal that fabric coated with 10 BLs of BPEI/Laponite produces up to 6 wt % char at 500 degrees C, which is almost 1 order of magnitude greater than that of untreated fabric. This initial study demonstrates that polymer/clay assemblies could improve the thermal stability of cotton and may be useful for fire safety applications. PMID- 20355872 TI - Significant carrier concentration changes in native electrodeposited ZnO. AB - We show that unintentional hydrogen doping of ZnO during the electrodeposition process can impact the material's carrier concentration as significantly as others have reported for intentional extrinsic doping. Mott-Schottky analyses on the natively n-type electrodeposits show a decrease in the carrier concentrations from 10(21) to 10(18) cm(-3) with increasing overpotential. A strong link exists between larger optical band gaps (determined from diffuse reflectance spectroscopy) and higher carrier concentrations, which suggests that hydrogen based doping underlies the n-type conductivity (Moss-Burstein effect). We propose that kinetic defects introduced during growth at larger overpotentials compete with hydrogen doping, thereby leading to lower net carrier concentrations. This has important implications for using the deposition potential to tune other electrodeposit properties such as the growth rate and morphology. PMID- 20355873 TI - Novel inorganic host layered double hydroxides intercalated with guest organic inhibitors for anticorrosion applications. AB - Zn-Al and Mg-Al layered double hydroxides (LDHs) loaded with quinaldate and 2 mercaptobenzothiazolate anions were synthesized via anion-exchange reaction. The resulting compounds were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Spectrophotometric measurements demonstrated that the release of organic anions from these LDHs into the bulk solution is triggered by the presence of chloride anions, evidencing the anion-exchange nature of this process. The anticorrosion capabilities of LDHs loaded with organic inhibitors toward the AA2024 aluminum alloy were analyzed by electrochemical impedance spectroscopy. A significant reduction of the corrosion rate is observed when the LDH nanopigments are present in the corrosive media. The mechanism by which the inhibiting anions can be released from the LDHs underlines the versatility of these environmentally friendly structures and their potential application as nanocontainers in self-healing coatings. PMID- 20355874 TI - Cross-linkable molecular glasses: low dielectric constant materials patternable in hydrofluoroethers. AB - We report a new approach to solution-processable low-dielectric-constant (low-k) materials including photolithographic patterning of these materials in chemically benign and environmentally friendly solvents. A series of semiperfluorinated molecular glasses with styrenic substituents were successfully synthesized. These small molecular materials were thermally stable up to 400 degrees C and also exhibited an amorphous nature, which is essential to forming uniform films. Differential scanning calorimetry studies revealed that a cross-linking reaction occurred in the presence of acid, resulting in the formation of robust polymeric films. Atomic force microscopy images of the cross-linked films showed uniform and pinhole-free surface properties. Dielectric constants determined by a capacitance measurement were 2.6-2.8 (100 kHz) at ambient conditions, which are comparable to other polymeric low-k materials. The incorporation of semiperfluorinated substituents was effective in decreasing the dielectric constant; in particular, the fluorinated alkyl ether structure proved best. In addition, the fluorinated substituents contributed to good solubility in hydrofluoroether (HFE) solvents, which enabled the successful photolithographic patterning of those materials in HFEs down to a submicrometer scale. PMID- 20355875 TI - Orderly arranged NLO materials based on chromophore-containing dendrons on exfoliated layered templates. AB - Three chromophore-containing dendrons were intercalated into montmorillonite layered silicates via an ion-exchange process. Enlarged d spacings ranging from 50 to 126 A were achieved for these novel organoclays. After the organoclays were blended with a polyimide, the steric bulkiness of the dendrons and the interaction between dendron and polyimide resulted in an ordered morphology. The orderly arranged nanocomposites were characterized by a UV-visible spectrophotometer, a variable-temperature infrared spectrometer, and electro optical modulation. The dendrons in layered silicates were capable of undergoing a critical conformational change into an ordered structure, indicated by the drastic changes of interlayer distances at certain packing densities. Electro optical coefficients increased sharply from 0 to 6 pm/V while the conformational change occurred. Furthermore, the addition of a polyimide capable of interaction induced orientation was found to exert an enhancing effect on the degree of the noncentrosymmetric alignment. PMID- 20355876 TI - Monitoring polymer properties using shear horizontal surface acoustic waves. AB - Real-time, nondestructive methods for monitoring polymer film properties are increasingly important in the development and fabrication of modern polymer containing products. Online testing of industrial polymer films during preparation and conditioning is required to minimize material and energy consumption, improve the product quality, increase the production rate, and reduce the number of product rejects. It is well-known that shear horizontal surface acoustic wave (SH-SAW) propagation is sensitive to mass changes as well as to the mechanical properties of attached materials. In this work, the SH-SAW was used to monitor polymer property changes primarily dictated by variations in the viscoelasticity. The viscoelastic properties of a negative photoresist film were monitored throughout the ultraviolet (UV) light-induced polymer cross linking process using SH-SAW delay line devices. Changes in the polymer film mass and viscoelasticity caused by UV exposure produced variations in the phase velocity and attenuation of the SH-SAW propagating in the structure. Based on measured polymer-coated delay line scattering transmission responses (S(21)) and the measured polymer layer thickness and density, the viscoelastic constants c(44) and eta(44) were extracted. The polymer thickness was found to decrease 0.6% during UV curing, while variations in the polymer density were determined to be insignificant. Changes of 6% in c(44) and 22% in eta(44) during the cross linking process were observed, showing the sensitivity of the SH-SAW phase velocity and attenuation to changes in the polymer film viscoelasticity. These results indicate the potential for SH-SAW devices as online monitoring sensors for polymer film processing. PMID- 20355877 TI - Phase inversion in polylactide/soybean oil blends compatibilized by poly(isoprene b-lactide) block copolymers. AB - Renewable composites were prepared by melt blending of polylactide and soybean oil. The blend morphology was tuned by the addition of poly(isoprene-b-lactide) block copolymers. Due to the extreme difference in the viscosities of soybean oil and polylactide, a critical block copolymer composition was found to induce a phase inversion point at which the minor soybean oil phase became the matrix surrounding polylactide particles. This transition was due to the thermodynamic interactions between the block copolymer and the two phases and shear forces acting on the mixture during blending. The size of the soybean oil droplets in the polylactide matrix was also highly dependent on the block copolymer composition. In binary polylactide/soybean oil blends, there was a limiting concentration of soybean oil that could be incorporated into the polylactide matrix (6% of the total blend weight), which could be increased up to 20% by the addition of block copolymers. PMID- 20355878 TI - Complement activation by polymers carrying hydroxyl groups. AB - Hydrogels of polymers carrying surface hydroxyl groups strongly activate the complement system through the alternative pathway, although it has also been reported that solutions of polymers do not. To address these curious, inconsistent results, we examined the effect of polymer states, either immobilized on a surface or soluble in serum, on the complement activation using a surface plasmon resonance apparatus and enzyme-linked immunosorbent assay. We clearly showed that dextran- and poly(vinyl alcohol)-immobilized surfaces strongly activated the complement system but that soluble polymers could not, even when the amounts of the soluble polymers added to serum were 4-2000 times higher than those on the polymer-immobilized surfaces. PMID- 20355879 TI - Encapsulation of 2-3-nm-sized ZnO quantum dots in a SiO2 matrix and observation of negative photoconductivity. AB - Quantum dots (QDs) of ZnO of 2-4 nm size have been encapsulated within a SiO(2) matrix using aqueous chemically grown ZnO nanoparticles in a precursor of tetraethyl orthosilicate. The microstructure shows almost a uniform embedment of the QDs in the SiO(2) matrix, resulting in a ZnO QDs-SiO(2) composite structure. The photocurrent transients of the composite show an instant fall in the current followed by an exponential decay under ultraviolet (UV) illumination, causing negative photoconductivity (NPC), in contrast to the positive photoconductivity in only ZnO nanoparticles. The interface defect states due to the presence of the SiO(2) network around ZnO act as charge trap centers for the photoexcited electrons and are responsible for the NPC. The presence of interface-trapped charges under UV illumination has been further confirmed from capacitance-voltage measurements. PMID- 20355880 TI - Core-shell structures of silica-organic pigment nanohybrids visualized by electron spectroscopic imaging. AB - Energy-filtering electron transmission spectroscopy observation has been achieved to elucidate the nanostructures of powdery nanohybrids, which were produced by the dry mechanical milling of organic pigments and silica nanoparticles. The hybrids possess core-shell structures, irrespective of the levels of aggregation of primary particles, whereas hollow sites of aggregates of primary silica particles were filled with the pigment, leading to the locally concentrated distribution of the pigment to reduce the surface areas of the hybrids. The results imply that nanohybridization is referred to as the buildup method, although mechanical tools and procedures are quite the same as those for the conventional breakdown method. PMID- 20355881 TI - Structural colored liquid membrane without angle dependence. AB - We have demonstrated for the first time that condensed gel particle suspensions in amorphous-like states display structural color with low angle dependence. This finding is in contrast to the common understanding that a periodic dielectric structure is fundamental to photonic band gap (PBG) production, and it validates the theory that a "tight bonding model" that is applicable to semiconductor systems can also be applied to photonic systems. More practically, this structural colored suspension represents a promising new material for the manufacture of reflective full-color displays with a wide viewing angle and nonfading color materials. This liquid system shows promise as a display material because electronic equipment used for display systems can easily be filled with the liquid in the same way that liquid crystals are currently used. PMID- 20355882 TI - A metal matrix composite prepared from electrospun TiO2 nanofibers and an Al 1100 alloy via friction stir processing. AB - Electrospun TiO2 nanofibers, consisting of anatase phase TiO2 single-crystalline crystallites with sizes of approximately 10 nm, were impregnated into an Al 1100 alloy by the technique of friction stir processing (FSP). The studies of the resulting TiO2-Al composite revealed that the electrospun TiO2 nanofibers with diameters of approximately 200 nm were broken into nanoparticles during FSP; the in situ generated pristine surfaces led to the interfacial reaction between TiO2 and Al and resulted in the formation of strong interfaces between the electrospun TiO2 nanoparticles and the Al 1100 matrix. This was evidenced by the fact that the filler-matrix fracture always occurred on the Al matrix side in the interfacial region. Consequently, the TiO2-Al composite made from the electrospun TiO2 nanofibers possessed a significantly higher Vickers hardness than that made from a commercially available anatase phase TiO2 nanopowder, of which the organic and/or carbonaceous contaminants on the surface impeded the interfacial reaction between TiO2 and Al during FSP. PMID- 20355883 TI - Reversibly cross-linked polymer gels as healing agents for epoxy-amine thermosets. AB - The Diels-Alder reaction was used to develop a reversibly cross-linking gel as a healing agent for traditional epoxy-amine thermosets. Direct application of the reversibly cross-linking network to a crack surface in an epoxy-amine thermoset resulted in the recovery of 37% of the initial epoxy-amine network's strength. Composites in which the reversibly cross-linking gel was incorporated as a secondary particulate phase recovered 21% of the initial composite strength after the first healing cycle, with healing possible up to five times. PMID- 20355884 TI - Polyelectrolyte multilayered nanofilms as a novel approach for the protection of hydrogen storage materials. AB - This work describes the encapsulation of hydrogen storage materials from organic solvents. Due to complex formation the shell provides stability and selective permeability. Specifically, sodium borohydride particles were encapsulated within polymer films by the layer-by-layer self-assembly of oppositely charged polyelectrolytes (polyethyleneimine and poly(acrylonitrile-co-butadiene-co acrylic acid)). The polymer nanofilm fabrication was performed using dichloromethane as a working media. IR spectroscopy was applied to investigate the chemical interaction between the polyelectrolytes. The multilayer film preparation was verified by Z-potential measurements, scanning electron microscopy, and confocal laser microscopy. The stability of sodium borohydride protected with a polyelectrolyte shell was increased compared to that of the pure material under ambient conditions. PMID- 20355885 TI - 3-[[3-(Triethoxysilyl)propyl]amino]propane-1-sulfonic acid-poly(vinyl alcohol) cross-linked zwitterionic polymer electrolyte membranes for direct methanol fuel cell applications. AB - Recently, organic-inorganic nanocomposite zwitterionic polymer electrolyte membranes (PEMs) have attracted remarkable interest for application to the direct methanol fuel cell (DMFC) operated at intermediate temperature (100-200 degrees C). In this paper, we report the synthesis of an organic-inorganic hybrid zwitterionomer silica precursor with ammonium and sulfonic acid functionality by the ring-opening of 3-propanesultone under mild heating conditions and the preparation procedure of a proton-conductive and stable organic-inorganic zwitterion-poly(vinyl alcohol) (PVA) cross-linked PEM by sol-gel in aqueous media. Developed PEMs were extensively characterized by studying their physicochemical and electrochemical properties under DMFC operating conditions. These membranes were designed to possess all of the required properties of a proton-conductive membrane, namely, reasonable swelling, good mechanical, dimensional, and oxidative strength, flexibility, and low methanol permeability along with reasonable proton conductivity (4.85 x 10(-2) S cm(-1)) due to zwitterionic functionality. Moreover, from the selectivity parameter among all developed membranes, ZI-70 [zwitterionomer membrane with 70 wt % of PVA of 3-[[3 (triethoxysilyl)propyl]amino]propane-1-sulfonic acid in the membrane matrix], exhibited the best results in comparison to the Nafion117 membrane for DMFC applications. PMID- 20355886 TI - Photochemical grafting and patterning of biomolecular layers onto TiO2 thin films. AB - TiO2 thin films are highly stable and can be deposited onto a wide variety of substrate materials under moderate conditions. We demonstrate that organic alkenes will graft to the surface of TiO2 when illuminated with UV light at 254 nm and that the resulting layers provide a starting point for the preparation of DNA-modified TiO2 thin films exhibiting excellent stability and biomolecular selectivity. By using alkenes with a protected amino group at the distal end, the grafted layers can be deprotected to yield molecular layers with exposed primary amino groups that can then be used to covalently link DNA oligonucleotides to the TiO2 surface. We demonstrate that the resulting DNA-modified surfaces exhibit excellent selectivity toward complementary versus noncomplementary target sequences in solution and that the surfaces can withstand 25 cycles of hybridization and denaturation in 8.3 M urea with little or no degradation. Furthermore, the use of simple masking methods provides a way to directly control the spatial location of the grafted layers, thereby providing a way to photopattern the spatial distribution of biologically active molecules to the TiO2 surfaces. Using Ti films ranging from 10 to 100 nm in thickness allows the preparation of TiO2 films that range from highly reflective to almost completely transparent; in both cases, the photochemical grafting of alkenes can be used as a starting point for stable surfaces with good biomolecular recognition properties. PMID- 20355887 TI - Design and color response of colorimetric multilumophore oxygen sensors. AB - The preparation of multilumophore colorimetric luminescent oxygen sensors exhibiting red-green, red-blue, and red-green-blue color space responses across oxygen partial pressures in the range of 0-760 Torr is described. We show how the relative lumophore concentration, emission lifetime, and permeability of the polymer host matrix to oxygen may be used to control both the color space response and the sensitivity of these sensors, thus enabling the device to be optimized for operation over a specific oxygen concentration range or application. The Commission Internationale de L'Eclairage (CIE) xy color space response and oxygen sensitivity of these experimental multilumophore sensors has been modeled using a combination of CIE color coordinates and Stern-Volmer quenching kinetics, and generally good agreement between the experimental and modeled response is obtained. This approach will therefore provide a useful preexperimentation tool for the design of sensors with specific response characteristics. PMID- 20355888 TI - Development and testing of hierarchically wrinkled coatings for marine antifouling. AB - We report on the formation and testing of novel marine coatings comprising hierarchically wrinkled surface topographies (HWTS) having wrinkles of different length scales (generations) ranging from tens of nanometers to a fraction of a millimeter. The individual wrinkle generations are arranged in nested patterns, where each larger wrinkle resides underneath and represents a scaled-up version of the smaller wrinkle. We present and discuss results from field tests in seawater and laboratory experiments. The results of our field tests reveal that while coatings with flat topographies foul after relatively short time periods (4 15 weeks), the HWST coatings with the same chemistries as flat coatings remain relatively free of biofouling even after prolonged exposure to seawater (18 months). In contrast to flat coatings, the HWST substrates are not colonized by barnacles. These observations suggest that surface topography plays a dominant role in governing the coating defense against barnacle fouling even without fine tuning the chemical composition of the overcoat. Laboratory experiments indicate that settlement of zoospores of the green alga Ulva and the strength of attachment of sporelings (young plants) depend on the chemical composition of the coating as well as surface topography. PMID- 20355889 TI - Cobalt-containing polyimides for moisture sensing and absorption. AB - A modified polyimide has been created that both senses and absorbs moisture. The material was prepared by introducing cobalt(II) chloride, a well-known moisture sensing and absorbing metal salt, into a polyimide. The final polymer was found to be fully cured, retaining the metal without any leeching, and was thermally stable. Furthermore, the material underwent a visible color change when exposed to moisture and reverted back to the original color when subsequently dried. The total moisture absorbed was measured with a quartz crystal microbalance. The amount of moisture absorption was found to be proportional to the relative humidity, and the modified polymer was found to have up to 3 times greater moisture absorption compared to the unmodified polymer. PMID- 20355890 TI - New insights into the fundamental chemical nature of ionic liquid film formation on magnesium alloy surfaces. AB - Ionic liquids (ILs) based on trihexyltetradecylphosphonium coupled with either diphenylphosphate or bis(trifluoromethanesulfonyl)amide have been shown to react with magnesium alloy surfaces, leading to the formation a surface film that can improve the corrosion resistance of the alloy. The morphology and microstructure of the magnesium surface seems critical in determining the nature of the interphase, with grain boundary phases and intermetallics within the grain, rich in zirconium and zinc, showing almost no interaction with the IL and thereby resulting in a heterogeneous surface film. This has been explained, on the basis of solid-state NMR evidence, as being due to the extremely low reactivity of the native oxide films on the intermetallics (ZrO2 and ZnO) with the IL as compared with the magnesium-rich matrix where a magnesium hydroxide and/or carbonate inorganic surface is likely. Solid-state NMR characterization of the ZE41 alloy surface treated with the IL based on (Tf)2N(-) indicates that this anion reacts to form a metal fluoride rich surface in addition to an organic component. The diphenylphosphate anion also seems to undergo an additional chemical process on the metal surface, indicating that film formation on the metal is not a simple chemical interaction between the components of the IL and the substrate but may involve electrochemical processes. PMID- 20355891 TI - Blood interactions with noble metals: coagulation and immune complement activation. AB - Noble metals are interesting biomaterials for a number of reasons, e.g., their chemical inertness and relative mechanical softness, silver's long known antimicrobial properties, and the low allergenic response shown by gold. Although important for the final outcome of biomaterials, little is reported about early events between pure noble metals and blood. In this article, we used whole blood in the "slide chamber model" to study the activation of the immune complement activation, generation of thrombin/antithrombin (TAT) complexes, and platelet depletion from blood upon contact with silver (Ag), palladium (Pd), gold (Au), titanium (Ti), and Bactiguard, a commercial nanostructured biomaterial coating comprised of Ag, Pd, and Au. The results show the highest TAT generation and platelet depletion on Ti and Au and lower on Pd, Ag, and the Bactiguard coating. The immune complement factor 3 fragment (C3a) was generated by the surfaces in the following order: Ag > Au > Pd > Bactiguard > Ti. Quartz crystal microbalance adsorption studies with human fibrinogen displayed the highest deposition to Ag and the lowest onto the Bactiguard coating. The adsorbed amounts of fibrinogen did not correlate with thrombogenicity in terms of TAT formation and platelet surface accumulation in blood. The combined results suggest, hence, that noble metal chemistry has a different impact on the protein adsorption properties and general blood compatibility. The low thrombogenic response by the Bactiguard coating cannot be explained by any of the single noble metal properties but is likely a successful combination of the nanostructure, nanogalvanic effects, or combinatory chemical and physical materials properties. PMID- 20355892 TI - Gold, palladium, and gold-palladium alloy nanoshells on silica nanoparticle cores. AB - The synthesis of gold, palladium, and gold-palladium alloy nanoshells (approximately 15-20 nm thickness) was accomplished by the reduction of gold and palladium ions onto dielectric silica core particles (approximately 100 nm in diameter) seeded with small gold nanoparticles (approximately 2-3 nm in diameter). The size, morphology, elemental composition, and optical properties of the nanoshells were characterized using field-emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and ultraviolet-visible spectroscopy. The results demonstrate the successful growth of gold, palladium, and gold-palladium alloy nanoshells, where the optical properties systematically vary with the relative content of gold and palladium. The alloy nanoshells are being prepared for use in applications that stand to benefit from photoenhanced catalysis. PMID- 20355893 TI - Preparation of core/shell and hollow nanostructures of cerium oxide by electrodeposition on a polystyrene sphere template. AB - Core/shell nanostructures of polystyrene (PS)/CeO2 have been prepared on conductive glass substrates by using a novel electrochemical route consisting of (i) the electrophoretic deposition of a PS sphere monolayer on the substrate and (ii) the following potentiostatic electrodeposition of CeO2 on the PS sphere template in Ce(NO3)3 aqueous solutions. The structural morphologies of the deposit changed drastically depending on the Ce(NO3)3 concentration; i.e., spherical and needlelike shells were deposited. The deposit was formed only on the PS sphere surface because of an interaction between cationic cerium species and a sulfate group that was immobilized on the PS sphere surface. The spherical shell layer was assigned as CeO2, and the needlelike shells were composed of Ce(OH)3 needles formed on the CeO2 layer surface, indicating that the deposit species changes from CeO2 to Ce(OH)3 during electrodeposition only in a 1 mM Ce3+ solution. Deposition of Ce(OH)3 would begin when electrogenerated hydrogen peroxide was consumed by decomposition under reductive conditions and could no longer oxidize Ce3+ ions. The corresponding CeO2 hollow shells were obtained by thermal elimination of the PS sphere core and transformation of Ce(OH)3 into CeO2 while keeping their original shapes. PMID- 20355894 TI - Immobilization of biomolecules on the surface of electrospun polycaprolactone fibrous scaffolds for tissue engineering. AB - To make polycaprolactone (PCL) more suitable for tissue engineering, PCL in the form of electrospun fibrous scaffolds was first modified with 1,6 hexamethylenediamine to introduce amino groups on their surface. Various biomolecules, i.e., collagen, chitosan, and Gly-Arg-Gly-Asp-Ser (GRGDS) peptide, were then immobilized on their surface, with N,N'-disuccinimidylcarbonate being used as the coupling agent. Dynamic water contact angle measurement indicated that the scaffold surface became more hydrophilic after the aminolytic treatment and the subsequent immobilization of the biomolecules. The appropriateness of these PCL fibrous scaffolds for the tissue/cell culture was evaluated in vitro with three different cell lines, e.g., mouse fibroblasts (L929), human epidermal keratinocytes (HEK001), and mouse calvaria-derived preosteoblastic cells (MC3T3 E1). Both the neat and the modified PCL fibrous scaffolds released no substances in the levels that were harmful to these cells. Among the various biomolecule immobilized PCL fibrous scaffolds, the ones that had been immobilized with type I collagen, a Arg-Gly-Asp-containing protein, showed the greatest ability to support both the attachment and the proliferation of all of the investigated cell types, followed by those that had been immobilized with GRGDS peptide. PMID- 20355895 TI - Engineering the microstructure of organic energetic materials. AB - The initiation sensitivity is highly dependent on void structures within an energetic material. It is technically feasible to modify the initiation sensitivity by lithographically defining the size and distribution of included voids on the micro- and nanoscale. We proposed a method to pattern organic energetic materials using microcontact printing of self-assembled monolayers. Pentaerythritol tetranitrate is spin-coated from solution as films onto patterned self-assembled monolayers. Images are presented for arbitrary patterns created based on the surface chemistry and concentration of the energetic material. PMID- 20355896 TI - Enhanced electrical conductivity of nanocomposites containing hybrid fillers of carbon nanotubes and carbon black. AB - Nanocomposites reinforced with hybrid fillers of carbon nanotubes (CNTs) and carbon black (CB) are developed, aiming at enhancing the electrical conductivity of composites with balanced mechanical properties while lowering the cost of the final product. Epoxy-based nanocomposites were prepared with varying combinations of CNTs and CB as conducting fillers, and their electrical and mechanical properties were evaluated. It was shown that the addition of CNTs in CB composites enhanced the electrical conductivity of composites: a low percolation threshold was achieved with 0.2 wt % CNTs and 0.2 wt % CB particles. The CB particles also enhanced the ductility and fracture toughness of nanocomposites, confirming the synergistic effect of CB as a multifunctional filler. The novelty of this work lies in the synergy arising from the combination of two conducting fillers with unique geometric shapes and aspect ratios as well as different dispersion characteristics, which have not been specifically considered previously. PMID- 20355897 TI - Nonaqueous TiO2 nanoparticle synthesis: a versatile basis for the fabrication of self-supporting, transparent, and UV-absorbing composite films. AB - A successful strategy to obtain self-supporting (100 microm), UV-absorbing, and, in the visible region, highly transparent TiO2-poly(methyl methacrylate) (PMMA) films was developed. The 15 nm large anatase TiO2 nanocrystals were prepared in a nonaqueous sol-gel approach involving the mixing of Ti(O(i)Pr)4 and benzyl alcohol. The surfaces of the resulting particles were modified with minute amounts of organic ligands in order to make the particles easily dispersible in nonpolar media like xylene and dichloromethane and compatible with PMMA, a polymer of high optical transparency and considerable technical importance. The empirical optimization process of composite fabrication was supplemented by fundamental studies of the crystallization and growth mechanism of anatase particles in a nonaqueous medium. After the preparation of corresponding nanocomposites, the materials were investigated with respect to their UV absorption capability, optical transparency in the visible-wavelength region, and photodegradation. PMID- 20355898 TI - Influence of salt on the aqueous lubrication properties of end-grafted, ethylene glycol-based self-assembled monolayers. AB - We have investigated the influence of a high-concentration salt solution (1 M NaCl) on the aqueous lubrication properties of ethylene glycol-based molecules, namely, alpha-methoxy-omega-mercaptopoly(ethylene glycol) (MW 5000 Da) and alpha methoxy-omega-mercaptoheptakis(ethylene glycol) (MW 356 Da), which have been end grafted onto polycrystalline gold surfaces at high surface density. Macroscopic scale, yet nondestructive, pin-on-disk tribometry experiments revealed that a high concentration of sodium chloride is deleterious to the aqueous lubricating properties of both films under low-sliding-speed conditions. This behavior was observed to be closely associated with the more collapsed conformation of surface grafted poly(ethylene glycol) polymer chains in concentrated salt solutions, as confirmed by quartz-crystal microbalance measurements. PMID- 20355899 TI - Surface-fluorinated proton-exchange membrane with high electrochemical durability for direct methanol fuel cells. AB - Random disulfonated poly(arylene ether sulfone)-silica nanocomposite (FSPAES SiO2) membranes were physicochemically tuned via surface fluorination. Surface fluorination for 30 min converted about 20% of the C-H bonds on the membrane surface into C-F bonds showing hydrophobicity and electronegativity at the same time. The membranes with hydrophobic surface properties showed high dimensional stability and low methanol permeability when hydrated for direct methanol fuel cell applications. In particular, the surface enrichment of fluorine atoms led to anisotropic swelling behavior, associated with a stable electrode interface formation. Interestingly, in spite of the use of a random copolymer as a polymer matrix, the low surface free energy of the C-F bonds induced a well-defined continuous ionic channel structure, similar to those of multiblock copolymers. In addition to the morphological transition, fluorine atoms with high electron withdrawing capability promoted the dissociation of sulfonic acid (-SO3H) groups. Consequently, FSPAES-SiO2 membranes exhibited improved proton conductivity. Thus, FSPAES-SiO2 membranes exhibited significantly improved single-cell performances (about 200%) at a constant voltage of 0.4 V in comparison with those of Nafion 117 and nonfluorinated membranes. Surprisingly, their good electrochemical performances were maintained with very low nonrecovery loss over the time period of 1400 h and interfacial resistances 380% times lower than those of conventional membrane-electrode assemblies comprising the control hydrocarbon membrane and a Nafion binder for the electrodes. PMID- 20355900 TI - Fused-ring pyrazine derivatives for n-type field-effect transistors. AB - Three new fused-ring pyrazine derivatives end-functionalized with trifluoromethylphenyl groups have been synthesized. The effect of a fused-ring pyrazine core on the thermal, electronic, optical, thin film morphology, and organic field-effect transistor (OFET) properties was investigated both experimentally and theoretically. Electrochemistry measurements and density functional theory calculations suggest that the pyrazine core plays a significant role in tuning the electron affinities of these compounds. The optical absorption and fluorescence properties are also sensitive to the pyrazine core. The OFET devices based on the fused-ring pyrazine compounds exhibit electron mobilities as high as ca. 0.03 cm(2) V(-1) s(-1) under nitrogen, and their performance is sensitive to the pyrazine core. The larger pyrazine core leads to a lower LUMO level and lower reorganization energy, to more ordered thin film morphology with larger grain size, and finally to higher mobilities. PMID- 20355901 TI - Microstructural effects on charge-storage properties in MnO2-based electrochemical supercapacitors. AB - The charge-storage mechanism in manganese dioxide (MnO2)-based electrochemical supercapacitors was investigated and discussed toward prepared MnO2 microstructures. The preparation of a series of MnO2 allotropic phases was performed by following dedicated synthetic routes. The resulting compounds are classified into three groups depending on their crystal structures based on 1D channels, 2D layers, or 3D interconnected tunnels. The 1D group includes pyrolusite, ramsdellite, cryptomelane, Ni-doped todorokite (Ni-todorokite), and OMS-5. The 2D and 3D groups are composed of birnessite and spinel, respectively. The prepared MnO2 powders were characterized using X-ray diffraction, scanning electron microscopy, the Brunauer-Emmett-Teller technique, cyclic voltammetry (CV), and electrochemical impedance spectroscopy. The influence of the MnO2 microstructure on the electrochemical performance of MnO2-based electrodes is commented on through the specific surface area and the electronic and ionic conductivities. It was demonstrated that the charge-storage mechanism in MnO2 based electrodes is mainly faradic rather than capacitive. The specific capacitance values are found to increase in the following order: pyrolusite (28 Fx g(-1)) < Ni-todorokite < ramsdellite < cryptomelane < OMS-5 < birnessite < spinel (241 Fx g(-1)). Thus, increasing the cavity size and connectivity results in the improvement of the electrochemical performance. In contrast with the usual assumption, the electrochemical performance of MnO2-based electrodes was not dependent on the specific surface area. The electronic conductivity was shown to have a limited impact as well. However, specific capacitances of MnO2 forms were strongly correlated with the corresponding ionic conductivities, which obviously rely on the microstructure. The CV experiments confirmed the good stability of all MnO2 phases during 500 charge/discharge cycles. PMID- 20355902 TI - Photocatalytic activity for hydrogen evolution of electrospun TiO2 nanofibers. AB - We report herein a simple procedure for the fabrication of TiO2 nanofibers by the combination of electrospinning and sol-gel techniques by using poly(vinylpyrrolidone) (PVP), titanium(IV) butoxide, and acetylacetone in methanol as a spinning solution. TiO2 nanofibers (260-355 nm in diameter), with a bundle of nanofibrils (20-25 nm in diameters) aligned in the fiber direction, or particle-linked structures were obtained from the calcination of as-spun TiO2/PVP composite fibers at temperatures ranging from 300 to 700 degrees C. These nanofibers were utilized as photocatalysts for hydrogen evolution. The nanofiber photocatalyst calcined at 450 degrees C showed the highest activity among the TiO2 nanofibers tested such as ones prepared by the hydrothermal method and anatase nanoparticles (Ishihara ST-01). These results indicate that one dimensional electrospun nanofibers with highly aligned bundled nanofibrils are beneficial for enhancement of the crystallinity, large surface area, and higher photocatalytic activity. PMID- 20355903 TI - Efficient dye-sensitized solar cells with catalytic multiwall carbon nanotube counter electrodes. AB - We report the successful application of multiwall carbon nanotubes (CNTs) as electrocatalysts for triiodide reduction in a dye-sensitized solar cell (DSSC). Defect-rich edge planes of bamboolike-structure multiwall CNTs facilitate the electron-transfer kinetics at the counter electrode-electrolyte interface, resulting in low charge-transfer resistance and an improved fill factor. In combination with a dye-sensitized TiO2 photoanode and an organic liquid electrolyte, a multiwall CNT counter-electrode DSSC shows 7.7% energy conversion efficiency under 1 sun illumination (100 mW/cm(2), air mass 1.5 G). The short term stability test at moderate conditions confirms the robustness of CNT counter electrode DSSCs. PMID- 20355904 TI - Preparation of superhydrophobic coatings on zinc as effective corrosion barriers. AB - Stable superhydrophobic films with a contact angle of 151 +/- 2 degrees were prepared on zinc substrates by a simple immersion technique into a methanol solution of hydrolyzed 1H,1H,2H,2H-perfluorooctyltrichlorosilane [CF3(CF2)5(CH2)2SiCl3, PFTS] for 5 days at room temperature followed by a short annealing at 130 degrees C in air for 1 h. The superhydrophobic film provides an effective corrosion-resistant coating for the zinc interface when immersed in an aqueous solution of sodium chloride (3% NaCl) for up to 29 days. The corrosion process was investigated by following the change of the water contact angle over time and by electrochemical means. The results are compared to those of unprotected zinc interfaces. PMID- 20355905 TI - Efficient green solar cells via a chemically polymerizable donor-acceptor heterocyclic pentamer. AB - In this contribution, we report on bulk-heterojunction solar cells using a solution-processable neutral green conjugated copolymer based on 3,4 dioxythiophene and 2,1,3-benzothiadiazole as the donor and [6,6]phenyl-C61 butyric acid methyl ester (PCBM) as the acceptor. We have found that the short circuit current is very sensitive to the composition of the donor-acceptor blend and it increases with increasing acceptor concentration. The device with a donor acceptor ratio of 1:8 gives the best performance with a short-circuit current of 5.56 mA/cm(2), an open-circuit voltage of 0.77 V, and a power conversion efficiency of 1.9% under AM 1.5 solar illumination. The incident photon-to current efficiency (IPCE) of the green solar cells shows two bands, one with a maximum of 57% in the UV region corresponding to absorption of PCBM and a second one with a maximum of 42% at longer wavelengths corresponding to the absorption of the green polymer. PMID- 20355906 TI - Flexible magnetic microtubules structured by lipids and magnetic nanoparticles. AB - This study presents a microtubule that responds to a magnetic field. We made such a structure by incorporating iron oxide nanoparticles during the preparation of the microtubule. We found that the microtubule stretches its body when the magnetic field is applied and easily aligns with the direction of the applied magnetic field by rotating its body. When the magnetic field is removed, it loses its orientation and goes back to its original state by contraction. From the analysis of its magnetic response, we estimated that the magnetic microtubule had an elastic modulus of 33 MPa. Further analysis showed that the stretching and contracting of its body are due to its flexibility. PMID- 20355907 TI - A novel, fast-responding, indicator ink for thin film photocatalytic surfaces. AB - A new photocatalyst indicator ink based on methylene blue (MB) is described that allows the presence and activity of a thin (15 nm) photocatalytic film to be assessed in seconds. The ink is very stable (shelf life > 6 months) and the color change (blue to colorless) striking. The ink utilizes a sacrificial electron donor, glycerol, to trap the photogenerated holes, leaving the photogenerated electrons to react with MB to produce its reduced, leuco, form (LMB). The efficacy of the MB ink is due to the presence of acid in its formulation, which curtails significantly the otherwise usual, rapid reoxidation of LMB by ambient O2. PMID- 20355908 TI - Dual magnetobiochemical logic control of electrochemical processes based on local interfacial pH changes. AB - An electrode surface modified with a pH-sensitive polymeric brush was reversibly activated by local pH changes produced in situ by glucose oxidase associated with magnetic nanoparticles confined at the surface in the presence of an external magnet. The system mimics Boolean AND logic gate, with the magnetic and chemical input signals stimulating the electrochemical reactions at the switchable interface. Biomedical applications of the "smart" interface controlled by enzymatic reactions through local pH changes are anticipated in various implantable biomedical devices. PMID- 20355909 TI - Effect of the charge balance on high-efficiency blue-phosphorescent organic light emitting diodes. AB - The charge balance in blue-phosphorescent devices was studied using single carrier devices, and the results show that the transport is highly hole dominant. The effect of the charge balance on the device performance was further demonstrated using different electron-transport materials with different electron mobilities. By optimization of the charge balance, a maximum current efficiency of 60 Cd A(-1) at a luminance of 500 cd m(-2) was achieved. PMID- 20355910 TI - Composite polymer electrolyte containing ionic liquid and functionalized polyhedral oligomeric silsesquioxanes for anhydrous PEM applications. AB - A new type of supported liquid membrane was made by combining an ionic liquid (IL) with a Nafion membrane reinforced with multifunctional polyhedral oligomeric silsesquioxanes (POSSs) using a layer-by-layer strategy for anhydrous proton exchange membrane (PEM) application. The POSS was functionalized by direct sulfonation, and the sulfonated POSS (S-POSS) was incorporated into Nafion 117 membranes by the infiltration method. The resultant hybrid membrane shows strong ionic interaction between the Nafion matrix and the multifunctional POSS, resulting in increased glass transition temperature and thermal stability at very low loadings of S-POSS (1%). The presence of S-POSS has also improved the proton conductivity especially at low humidities, where it shows a marked increase due to its confinement in the ionic domains and promotes water uptake by capillary condensation. In order to achieve anhydrous conductivity, the IL 1-butyl-3 methylimidazolium bis(trifluoromethylsulfonyl)imide (BMI-BTSI) was incorporated into these membranes to provide proton conduction in the absence of water. Although the incorporation of an IL shows a plasticizing effect on the Nafion membrane, the S-POSS composite membrane with an IL shows a higher modulus at high temperatures compared to Nafion 117 and a Nafion-IL membrane, with significantly higher proton conductivity (5 mS/cm at 150 degrees C with 20% IL). This shows the ability of the multifunctional POSS and IL to work symbiotically to achieve the desirable proton conductivity and mechanical properties of such membranes by enhancing the ionic interaction within the material. PMID- 20355911 TI - Efficient surface-relief gratings in hydrogen-bonded polymer-azobenzene complexes. AB - We show that efficient photoinduced surface-relief gratings can be inscribed in polymer-azobenzene complexes which are bonded by phenol-pyridine hydrogen bonding. The grating inscription was studied as a function of chromophore concentration and the molecular weight of the host polymer, both of which can be easily tuned without demanding organic synthesis. Stable gratings with modulation depth as high as 440 nm and with diffraction efficiency exceeding 40% were inscribed in the equimolar complexes. Our results demonstrate that phenol pyridine hydrogen bonding not only allows one to increase the chromophore content until each polymer unit is occupied but is also sufficiently strong to induce mass migration of the polymer chains in a manner comparable to covalently functionalized polymers. PMID- 20355912 TI - Effect of a zirconium tungstate filler on the cure behavior of a cyanate ester resin. AB - In this work, the effect of a negative thermal expansion zirconium tungstate (ZrW2O8) filler on the cure behavior of a unique low-viscosity bisphenol E cyanate ester (BECy) is characterized by differential scanning calorimetry. The cure rate of BECy is found to increase upon the incorporation of ZrW2O8 particles, and the catalytic effect increases with increasing filler loading. The catalytic effect is primarily attributed to the presence and nature of hydroxyl groups on the ZrW2O8 particle surface. In comparison with BECy/ZrW2O8 composites of the same loading, silane-coated ZrW2O8 particles resulted in a higher value of the glass transition temperature (T(g)) and a delay in the onset of the cure. The ability of a phenomenological reaction model to describe the cure behavior of the composites is also examined. PMID- 20355913 TI - "Giant" hollow multilayer capsules by microfluidic templating. AB - Monodisperse microgels were synthesized by a microfluidic setup and used as a sacrificial template for the fabrication of "giant" hollow polyelectrolyte capsules with rigid walls consisting of covalently cross-linked polyelectrolytes and metal nanoparticles. First, a simple tubing-needle-based microfluidic system is utilized to produce size-monodisperse, degradable "giant" microgels consisting of dextran chains linked via carbonate esters. Second, these monodisperse microgels are subjected to a layer-by-layer coating of negatively charged platinum nanoparticles (Pt(NP)'s) and a positively charged diazoresin (DAR). Three bilayers of Pt(NP)'s and DAR are used to obtain a stable membrane on the microgels. Finally, the sacrificial dextran-based microgel cores are smoothly hydrolyzed and removed without rupture of the polyelectrolyte membrane due to the covalently linked hybrid polyelectrolyte/nanoparticle nature of the membrane. Scanning electron and confocal microscopy are used to characterize the capsules. The capability of encapsulating materials of interest is also shown by the addition of fluorescent polystyrene particles to the monomer mixture and subsequent visualization of embedded polystyrene particles in coated microgels after microfluidic polymerization and layer-by-layer coating. The obtained "giant" microcapsules are envisaged to be used as microreactors or drug-delivery systems. PMID- 20355914 TI - Carbon-nanotube-based materials for protein crystallization. AB - We report on the first use of carbon-nanotube-based films to produce crystals of proteins. The crystals nucleate on the surface of the film. The difficulty of crystallizing proteins is a major bottleneck in the determination of the structure and function of biological molecules. The crystallization of two model proteins and two medically relevant proteins was studied. Quantitative data on the crystallization times of the model protein lysozyme are also presented. Two types of nanotube films, one made with the surfactant Triton X-100 (TX-100) and one with gelatin, were tested. Both induce nucleation of the crystal phase at supersaturations at which the protein solution would otherwise remain clear; however, the gelatin-based film induced nucleation down to much lower supersaturations for the two model proteins with which it was used. It appears that the interactions of gelatin with the protein molecules are particularly favorable to nucleation. Crystals of the C1 domain of the human cardiac myosin binding protein-C that diffracted to a resolution of 1.6 A were obtained on the TX-100 film. This is far superior to the best crystals obtained using standard techniques, which only diffracted to 3.0 A. Thus, both of our nanotube-based films are very promising candidates for future work on crystallizing difficult-to crystallize target proteins. PMID- 20355915 TI - Fully atomistic molecular dynamics simulations of the behavior of a simple model of crude oil confined between graphene planes. AB - We present and discuss the results of molecular dynamics computer simulations of crude oil confined between graphene planes. The crude oil is represented as a mixture of alkanes having 6 Bisterpy(*+) <--> Bisterpy(0), which were slightly shifted to lower potentials in the LB films of metal-mediated coordination polymers. The film compositions were determined by using X-ray photoelectron spectroscopy. The as-prepared LB films showed strong stability and good electrochromic response upon the applied potential of -1.1 V vs Ag/AgCl and thus could act as potential materials in the development of redox-based molecular switches and display devices. PMID- 20355921 TI - Chemical synthesis of Bi(0.5)Sb(1.5)Te3 nanocrystals and their surface oxidation properties. AB - Bismuth-antimony-telluride alloy, Bi(0.5)Sb(1.5)Te3, nanocrystals (NCs) have been synthesized by direct chemical solution synthesis, in which the bismuth and antimony precursors, dissolved in a phenyl ether solution and coordinated with dodecanethiol, directly reacted with tellurium in trioctylphosphine. Transmission electron microscopy and X-ray diffraction (XRD) were used for the structure and morphology characterization of these NCs. Their XRD pattern evolution indicated that the reaction temperature plays a critical role in alloying and crystallization of Bi(0.5)Sb(1.5)Te3 NCs. X-ray photoelectron spectrometry was used to study the alloy states and surface oxidation. It is found that the choice of the capping ligands can be important and useful in protecting against the surface oxidation of Bi2Te3-type thermoelectrical nanomaterials. PMID- 20355922 TI - Effective variables to control the fill factor of organic photovoltaic cells. AB - Effective cell design variables having a large impact on the fill factor (FF) of organic photovoltaic cells (OPVCs) were systematically identified using a general device structure of ITO/PEDOT:PSS/P3HT + PCBM/LiF/Al. The results show that the characteristic properties of the organic layer, such as morphology and thickness, the regioregularity of the conjugated polymer, and the two interfaces between the electrodes and the blend layer have a large influence on the FF by affecting the series resistance (R(s)) and the shunt resistance (R(sh)). The systematic investigation described in this contribution provides a comprehensive understanding of the correlation between the device variables and R(s) and R(sh) and a way to control FF, which is critically important to achieving a high performance OPVC. PMID- 20355923 TI - Experimental studies on the interactions between Au nanoparticles and amino acids: bio-based formation of branched linear chains. AB - Biomacromolecules represent new structures employed for the fabrication, assembly, and subsequent use of nanomaterials for a variety of applications. By genetically selecting for the binding abilities of these bio-based molecules, the generation of materials with enhanced and environmentally sound properties is possible. Unfortunately, the level of understanding as to how the biomolecules bind and arrange on the nanomaterial surface is incomplete. Recent experimental and theoretical results suggest that the binding is dependent upon the peptide composition, sequence, and structure; however, these results were obtained for two-dimensional surfaces of the targeted inorganic material. Changing of the sample from two-dimensional targets to in solution three-dimensional nanomaterials presents a challenge because the level of analytical characterization for the latter system is minimal. Here we present our recent studies on the interactions between Au nanoparticles and the amino acid arginine. In our experimental design, the introduction of increasing concentrations of arginine to citrate-capped Au nanoparticles resulted in the formation of branched linear chains of the spherical nanomaterials. This assembly process was able to be monitored using UV-vis spectroscopy, transmission electron microscopy, and dynamic light scattering. The final results suggest that incomplete substitution of the original citrate surface passivant with the amino acid occurs, resulting in surface segregation of the two species. The segregation effect produces a dipole across the Au nanoparticle surface to drive the linear assembly of the materials in solution. Such results can possibly be exploited in understanding binding motifs and modes for biomolecules on the surface of functional nanomaterials. PMID- 20355924 TI - Synthesis and properties of sulfonated block copolymers having fluorenyl groups for fuel-cell applications. AB - A series of sulfonated poly(arylene ether sulfone)s (SPEs) block copolymers containing fluorenyl groups were synthesized. Bis(4-fluorophenyl)sulfone (FPS) and 2,2-bis(4-hydroxy-3,5-dimethylpheny)propane were used as comonomers for hydrophobic blocks, whereas FPS and 9,9-bis(4-hydroxyphenyl)fluorene were used as hydrophilic blocks. Sulfonation with chlorosulfonic acid gave sulfonated block copolymers with molecular weight (M(w)) higher than 150 kDa. Proton conductivity of the SPE block copolymer with the ion exchange capacity (IEC) = 2.20 mequiv/g was 0.14 S/cm [80% relative humidity (RH)] and 0.02 S/cm (40% RH) at 80 degrees C, which is higher or comparable to that of a perfluorinated ionomer (Nafion) membrane. The longer hydrophilic and hydrophobic blocks resulted in higher water uptake and higher proton conductivity. Scanning transmission electron microscopy observation revealed that phase separation of the SPE block copolymers was more pronounced than that of the SPE random copolymers. The SPE block copolymer membranes showed higher mechanical properties than those of the random ones. With these properties, the SPE block copolymer membranes seem promising for fuel-cell applications. PMID- 20355925 TI - Preparation, characterization, and sensing behavior of polydiacetylene liposomes embedded in alginate fibers. AB - Polydiacetylene (PDA)-doped calcium alginate fibers were created by the solution blending of polymerized 10,12-pentacosadiynoic acid liposomes with sodium alginate in water prior to extrusion. The liposomes maintained their blue color during wet spinning and drying of the fibers but changed to red with exposure to specific external stimuli (heat, solvent, and chemical). In the latter case, the color change only occurred when the fibers were sufficiently permeable for the reacting species to reach the interior. A parameter termed the "Raman response" (RR) has been developed to quantify the amount of PDA liposomes in each of two critical conformations within the fibers. The RR attributes a quantitative measure of PDA response to individual stimuli. This method provides advantages over the commonly used "colorimetric response" in systems where sample limitations and chromophore activity make UV-vis spectroscopic measurements difficult or inaccurate. PDA liposomes are shown to effectively add a versatile sensing component to alginate fibers. PMID- 20355926 TI - Mineralization of clay/polymer aerogels: a bioinspired approach to composite reinforcement. AB - Clay aerogels, ultra low density materials made via a simple freeze-drying technique, have shown much promise in broad applications because of their low densities, often in the same range as silica aerogels (0.03-0.3 g/cm(3),) but suffering from low mechanical strength. A bioinspired approach to mineralize an active polymer/clay aerogel composite is inspected, showing marked improvement of the mechanical properties with increasing modification. Further property improvement was achieved using a layer-by-layer approach to produce alternate layers of polymer and silica on the surface. PMID- 20355927 TI - Stable, ligand-doped, poly(bis-SorbPC) lipid bilayer arrays for protein binding and detection. AB - A continuous-flow microspotter was used to generate planar arrays of stabilized bilayers composed of the polymerizable lipid bis-SorbPC and dopant lipids bearing ligands for proteins. Fluorescence microscopy was used to determine the uniformity of the bilayers and to detect protein binding. After UV-initiated polymerization, poly(lipid) bilayer microarrays were air-stable. Cholera toxin subunit b (CTb) bound to an array of poly(lipid) bilayers doped with GM(1), and the extent of binding was correlated to the mole percentage of GM(1) in each spot. A poly(lipid) bilayer array composed of spots doped with GM(1) and spots doped with biotin-DOPE specifically bound CTb and streptavidin to the respective spots from a dissolved mixture of the two proteins. Poly(bis-SorbPC)/GM(1) arrays retained specific CTb binding capacity after multiple regenerations with a protein denaturing solution and also after exposure to air. In addition, these arrays are stable in vacuum, which allows the use of MALDI-TOF mass spectrometry to detect specifically bound CTb. This work demonstrates the considerable potential of poly(lipid) bilayer arrays for high-throughput binding assays and lipidomics studies. PMID- 20355928 TI - Superhydrophobic copper tubes with possible flow enhancement and drag reduction. AB - The transport of a Newtonian liquid through a smooth pipe or tube is dominated by the frictional drag on the liquid against the walls. The resistance to flow against a solid can, however, be reduced by introducing a layer of gas at or near the boundary between the solid and liquid. This can occur by the vaporization of liquid at a surface at a temperature above the Leidenfrost point, by a cushion of air (e.g. below a hovercraft), or by producing bubbles at the interface. These methods require a continuous energy input, but a more recent discovery is the possibility of using a superhydrophobic surface. Most reported research uses small sections of lithographically patterned surfaces and rarely considers pressure differences or varying flow rates. In this work we present a method for creating a uniform superhydrophobic nanoribbon layer on the inside of round copper tubes of millimetric internal radius. Two types of experiments are described, with the first involving a simultaneous comparison of four tubes with different surface finishes (as received, as received with hydrophobic coating, nanoribbon, and nanoribbon with a hydrophobic coating) under constant flow rate conditions using water and water-glycerol mixtures. The results show that the superhydrophobic nanoribbon with a hydrophobic coating surface finish allows greater flow at low pressure differences but that the effect disappears as the pressure at the inlet of the tube is increased. The second experiment is a simple visual demonstration of the low-pressure behavior using two nominally identical tubes in terms of length and cross-section, but with one tube possessing a superhydrophobic internal surface finish. In this experiment a reservoir is allowed to feed the two tubes with open ends via a T-piece and it is observed that, once flow commences, it preferentially occurs down the superhydrophobic tube. PMID- 20355929 TI - Modeling the water-bioglass interface by ab initio molecular dynamics simulations. AB - The hydration of the surface of a highly bioactive silicate glass was modeled using ab initio (Car-Parrinello) molecular dynamics (CPMD) simulations, focusing on the structural and chemical modifications taking place at the glass-water interface immediately after contact and on the way in which they can affect the bioactivity of these materials. The adsorption of a water dimer and trimer on the dry surface was studied first, followed by the extended interface between the glass and liquid water. The CPMD trajectories provide atomistic insight into the initial stages relevant to the biological activity of these materials: following contact of the glass with an aqueous (physiological) medium, the initial enrichment of the surface region in Na+ cations establishes dominant Na+-water interactions at the surface, which allow water molecules to penetrate into the open glass network and start its partial dissolution. The model of a Na/H exchanged interface shows that Ca2+-water interactions are mainly established after the dominant fraction of Na is leached into the solution. Another critical role of modifier cations was highlighted: they provide the Lewis acidity necessary to neutralize OH(-) produced by water dissociation and protonation of nonbridging oxygen (NBO) surface sites. The CPMD simulations also highlighted an alternative, proton-hopping mechanism by which the same process can take place in the liquid water film. The main features of the bioactive glass surface immediately after contact with an aqueous medium, as emerged from the simulations, are (a) silanol groups formed by either water dissociation at undercoordinated Si sites or direct protonation of NBOs, (b) OH(-) groups generally stabilized by modifier cations and coupled with the protonated NBOs, and (c) small rings, relatively stable and unopened even after exposure to liquid water. The possible role and effect of these sites in the bioactive process are discussed. PMID- 20355930 TI - Radiative cooling: lattice quantization and surface emissivity in thin coatings. AB - Nanodiamond powder (NDP), multiwall carbon nanotube (MWCNT), and carbon black (CB) were dispersed in an acrylate (AC) emulsion to form composite materials. These materials were coated on aluminum panels (alloy 3003) to give thin coatings. The active phonons of the nanomaterials were designed to act as a cooling fan, termed "molecular fan (MF)". The order of lattice quantization, as investigated by Raman spectroscopy, is MWCNT > CB >> NDP. The enhanced surface emissivity of the MF coating (as observed by IR imaging) is well-correlated to lattice quantization, resulting in a better cooling performance by the MWCNT-AC composite. MF coatings with different concentrations (0%, 0.4%, 0.7%, and 1%) of MWCNT were prepared. The equilibrium temperature lowering of the coated panel was observed with an increase in the loading of CNTs and was measured as 17 degrees C for 1% loading of MWCNT. This was attributed to an increased density of active phonons in the MF coating. PMID- 20355931 TI - Printed magnetic FePt nanocrystal films. AB - Patterned monolayers and multilayers of FePt nanocrystals were printed onto substrates by first assembling nanocrystals on a Langmuir-Blodgett (LB) trough and then lifting them onto prepatterned polydimethylsiloxane (PDMS) stamps, followed by transfer printing onto the substrate. Patterned features, including micrometer-size circles, lines, and squares, could be printed using this approach. The magnetic properties of the printed nanocrystal films were also measured using magnetic force microscopy (MFM). Room-temperature MFM could detect a remanent (permanent) magnetization from multilayer (>3 nanocrystals thick) films of chemically ordered L1(0) FePt nanocrystals. PMID- 20355932 TI - Asphaltene adsorption onto self-assembled monolayers of alkyltrichlorosilanes of varying chain length. AB - The adsorption of asphaltenes onto flat silica surfaces modified with self assembled monolayers (SAMs) of alkyltrichlorosilanes of varying thickness due to a variable number of carbon atoms (N(C)) has been studied by means of contact angle measurements, spectroscopic ellipsometry, and near-edge X-ray absorption fine structure spectroscopy. The extent of asphaltene adsorption was found to depend primarily on the ability of the SAM layer to shield the underlying silicon substrate from interacting with the asphaltenes present in solution. Specifically, asphaltene adsorption decreased with an increase in N(C) and/or an increase in SAM grafting density, sigma(SAM), (i.e., number of SAM molecules per unit area). The effect of the solvent quality on the extent of asphaltene adsorption was gauged by adsorbing asphaltenes from toluene, 1-methylnaphthalene, tetralin, decalin, and toluene-heptanes mixtures. The extent of asphaltene adsorption was found to increase proportionally with a decrease in the Hildebrand solubility parameter of the solvent. PMID- 20355933 TI - Mechanical properties of bare and protein-coated giant unilamellar phospholipid vesicles. A comparative study of micropipet aspiration and atomic force microscopy. AB - In this study, protein-coated giant phospholipid vesicles were used to model cell plasma membranes coated by surface protein layers that increase membrane stiffness under mechanical or osmotic stress. These changed mechanical properties like bending stiffness, membrane area compressibility modulus, and effective Young's modulus were determined by micropipet aspiration, while bending stiffness, effective Young's modulus, and effective spring constant of vesicles were analyzed by AFM. The experimental setups, the applied models, and the results using both methods were compared here. As demonstrated before, we found that bare vesicles were best probed by micropipet aspiration due to its high sensitivity. The mechanical properties of vesicles with protein surface layers were, however, better determined by AFM because it enables very local deformations of the membrane with barely any structural damage to the protein layer. Mechanical properties of different species of coating proteins, here streptavidin and avidin, could be clearly distinguished using this technique. PMID- 20355934 TI - Polypeptide-mediated switchable microarray of bacteria. AB - This paper describes a feasible solution for the bacterial cell death and contamination from cell division that occurs in microfluidic applications. The method adopts a smart thermoresponsive surface, highly resolved micropatterns, and surface-functionalized bacteria tagged with thermoresponsive molecules. We developed a method for controllable bacterial attachment and detachment using an elastin-like polypeptide (ELP). To create a smart surface with switchable properties, the surface of a glass substrate was conjugated with thermoresponsive ELP molecules. The attachment of bacterial cells to the ELP surface was induced by the hydrophobic affinity of the ELPs on the glass surface to tagged ELPs on the bacterial surface. A cell-repellent polymer was micropatterned to create a highly resolved space for specific bacterial adhesion. Reversible bacterial attachment and detachment was achieved by controlling the thermoresponsive phase transition of ELP molecules. Five different types of bacteria were successfully conjugated with ELPs and arrayed on the surface. The viability of the bacteria that had attached to the surface was evaluated by determining colony forming units of released bacteria on an agar plate. PMID- 20355936 TI - Effect of the incorporation of a low-band-gap small molecule in a conjugated vinylene copolymer: PCBM blend for organic photovoltaic devices. AB - The effect of the incorporation of a low-band-gap small-molecule BTD-TNP on the photovoltaic properties of vinylene copolymer P:PCBM bulk heterojunction solar cells has been investigated. The introduction of this small molecule increases both the short-circuit photocurrent and the overall power conversion efficiency of the photovoltaic device. The incident photon-to-current efficiency (IPCE) of the device based on P:PCBM:BTD-TNP shows two distinct bands, which correspond to the absorption bands of P:PCBM and BTD-TNP. Furthermore, it was found that the IPCE of the device has also been enhanced even at the wavelengths corresponding to the absorption band of P:PCBM, when the thermally annealed blend was used in the device. This indicates that the excitons that are generated in copolymer P are dissociated into charge carriers more effectively in the presence of the BTD TNP small molecule at the copolymer P:PCBM interface by energy transfer from P to the small molecule. Therefore, we conclude that the BTD-TNP small molecule acts as light-harvesting photosensitizer and also provides a path for the generated exciton in copolymer P toward the P:PCBM interface for efficient charge separation. The overall power conversion efficiency for the P:PCBM:BTD-TNP photovoltaic device is about 1.27%, which has been further enhanced up to 2.6%, when a thermally annealed blend layer is used. PMID- 20355935 TI - Strong, low-density nanocomposites by chemical vapor deposition and polymerization of cyanoacrylates on aminated silica aerogels. AB - Strong polymer-silica aerogel composites were prepared by chemical vapor deposition of cyanoacrylate monomers onto amine-modified aerogels. Amine-modified silica aerogels were prepared by copolymerizing small amounts of (aminopropyl)triethoxysilane with tetraethoxysilane. After silation of the aminated gels with hexamethyldisilazane, they were dried as aerogels using supercritical carbon dioxide processing. The resulting aerogels had only the amine groups as initiators for the cyanoacrylate polymerizations, resulting in cyanoacrylate macromolecules that were higher in molecular weight than those observed with unmodified silica and that were covalently attached to the silica surface. Starting with aminated silica aerogels that were 0.075 g/cm(3) density, composite aerogels were made with densities up to 0.220 g/cm(3) and up to 31 times stronger (flexural strength) than the precursor aerogel and about 2.3 times stronger than an unmodified silica aerogel of the same density. PMID- 20355937 TI - Growth of pagoda-topped tetragonal copper nanopillar arrays. AB - Growth of arrays of pagoda-topped tetragonal Cu nanopillar (length 1- 6 mum; width 150 +/- 25 nm) with {100} side faces on Au/glass is achieved by a simple electrochemical reduction of CuCl(2)(aq) by Al(s) in aqueous dodecyltrimethylammonium chloride. Field-emission measurement shows that the Cu nanopillars can emit electrons (10 muA cm(-2)) at a turn-on field of 12.4 V mum( 1) with a calculated field enhancement factor of 713. PMID- 20355938 TI - Trace detection of explosive particulates with a phosphole oxide. AB - Phosphole oxides exert the ability to detect explosives, especially nitroaromatic explosives such as 2,4,6-trinitrotoluene (TNT), by fluorescence quenching. In the image sensing of explosives sprayed with phosphole oxide, fluorescence quenching permits the visual determination of the lower detection limits of the nitroaromatic explosives in the nanogram level. PMID- 20355939 TI - Cellulose nanocrystal/gold nanoparticle composite as a matrix for enzyme immobilization. AB - A novel nanocomposite consisting of cellulose nanocrystals (CNCs) functionalized with gold nanoparticles (AuNPs) serving as an excellent support for enzyme immobilization with phenomenally high loading is presented in this work. As testing models, cyclodextrin glycosyl transferase (CGTase) and alcohol oxidase were conjugated on an activated CNC/AuNP matrix. This catalytic platform exhibits significant biocatalytic activity with excellent enzyme stability and without apparent loss of the original activity. The recovered specific activities were approximately 70% and 95% for CGTase and alcohol oxidase, respectively. This novel and inexpensive material is anticipated to extend to other enzymes, enhancing the enzyme loading and activity as well as the stability in both operation and storage. PMID- 20355940 TI - Microfluidic patterning of miniaturized DNA arrays on plastic substrates. AB - This paper describes the patterning of DNA arrays on plastic surfaces using an elastomeric, two-dimensional microcapillary system (muCS). Fluidic structures were realized through hot-embossing lithography using Versaflex CL30. Like elastomers based on poly(dimethylsiloxane), this thermoplastic block copolymer is able to seal a surface in a reversible manner, making it possible to confine DNA probes with a level of control that is unparalleled using standard microspotting techniques. We focus on muCSs that support arrays comprising up to 2 x 48 spots, each being 45 mum in diameter. Substrates were fabricated from two hard thermoplastic materials, poly(methylmethacrylate) and a polycyclic olefin (e.g., Zeonor 1060R), which were both activated with 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide hydrochloride and N-hydroxysuccinimide to mediate covalent attachment of DNA molecules. The approach was exemplified by using 0.25-32 muM solutions of amino-modified oligonucleotides labeled with either Cy3 or Cy5 fluorescent dye in phosphate-buffered saline, allowing for a direct and sensitive characterization of the printed arrays. Solutions were incubated for durations of 1 to >48 h at 22, 30, and 40 degrees C to probe the conditions for obtaining uniform spots of high fluorescence intensity. The length (l) and depth (d) of microfluidic supply channels were both important with respect to depletion as well as evaporation of the solvent. While selective activation of the substrate proved helpful to limit unproductive loss of oligonucleotides along trajectories, incubation of solution in a humid environment was necessary to prevent uncontrolled drying of the liquid, keeping the immobilization process intact over extended periods of time. When combined, these strategies effectively promoted the formation of high-quality DNA arrays, making it possible to arrange multiple probes in parallel with a high degree of uniformity. Moreover, we show that resultant arrays are compatible with standard hybridization protocols, which allowed for reliable discrimination of individual strands when exposed to a specific ssDNA target molecule. PMID- 20355941 TI - Silicon nanowires coated with silver nanostructures as ultrasensitive interfaces for surface-enhanced Raman spectroscopy. AB - Silver nanoparticles (Ag NPs) were chemically deposited on silicon nanowires (SiNWs), prepared using the vapor-liquid-solid (VLS) growth mechanism, using an in situ electroless metal deposition technique. The resulting SiNWs/Ag NPs composite interfaces showed large Raman scattering enhancement for rhodamine 6G (R6G) with a detection limit of 10(-14) M and an enhancement factor of 2.3 x 10(8). This large enhancement factor was attributed to the presence of "hot" spots on the SiNWs/Ag NPs substrate. PMID- 20355942 TI - Hydrodynamic transformation of a freestanding polymer nanosheet induced by a thermoresponsive surface. AB - Freestanding quasi-two-dimensional ultrathin films (e.g., 41 nm thick polymer nanosheets) were produced, on which stimuli-responsive 47 nm thick polymer brushes were constructed by atom transfer radical polymerization (ATRP) of poly(N isopropylacrylamide). The resulting surfaces of the multilayered polysaccharide ultrathin films were evaluated by ellipsometry, IR imaging, in situ variable temperature atomic force microscopy (AFM), and contact angle measurements. The morphological transformation of the freestanding polymer nanosheet bearing thermoresponsive polymer brushes was observed macroscopically through reversible structural color changes at the air-water interface. The dynamic shape change of the nanosheet was also monitored with the addition of a surfactant such as sodium n-dodecylsulfate to reduce the hydrophobicity of the surface. It was then demonstrated that the highly flexible freestanding polymer nanosheet is capable of acting as a unique platform for inducing stimuli-responsive behavior in nanomaterials. PMID- 20355943 TI - Trinity DNA detection platform by ultrasmooth and functionalized PEDOT biointerfaces. AB - An oligonucleotide-grafted poly(3,4-ethylenedioxythiophene) (PEDOT) thin film is developed for three DNA biosensor detection methods, including fluorescence, quartz crystal microbalance, and electrochemical methods. By electrocopolymerization of hydroxyl-functionalized EDOT and carboxylic functionalized EDOT in microemulsion solutions, ultrasmooth films with a controlled surface density of carboxylic groups are created. The probe oligonucleotides are immobilized on PEDOT thin films by using a N hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride coupling method. By monitoring the DNA hybridization efficiency on thin films with different oligonucleotide densities, the optimized density for DNA hybridization is obtained. The feasibility and limitation of using this platform for electrochemical detection are also discussed. PMID- 20355944 TI - Rapid synthesis of core/shell ZnS:Mn/Si nanotetrapods by a catalyst-free thermal evaporation route. AB - We report the fabrication of a hybrid all semiconductor core/shell nanotetrapod structure consisting of crystalline ZnS:Mn core and amorphous Si shell for the first time. The nanostructures were produced via a catalyst-free rapid thermal evaporation technique. Core/shell nanotetrapods were formed in two steps: (i) formation of the crystalline ZnS:Mn tetrapods and (ii) simultaneous surface adsorption of the in situ formed Si vapor species providing the amorphous shell. Crystalline tetrapod formation was guided by the formation of cubic structured ZnS octahedrons with four active (111) polar growth planes, which served as the favored growth site for the four wurtzite structured legs of the tetrapods. Choice of chloride salt as the source of dopant ion was crucial for the in situ generation of Si vapor. At elevated temperature, chloride salt reacted with the sulfur vapor to produce S2Cl2 gas that etched the Si wafers, generating Si vapor. Suppression of the surface-state-related blue emission was observed in the core/shell structures that clearly supported the formation of a shell layer. Elimination of the surface states ensured efficient energy transfer to the dopant Mn ionic state, resulting in the strong orange emission via (4)T(1)-(6)A(1) electronic transition. PMID- 20355945 TI - "Click chemistry" in tailor-made polymethacrylates bearing reactive furfuryl functionality: a new class of self-healing polymeric material. AB - This investigation reports the effective use of the Diels-Alder (DA) reaction, a "click reaction" in the preparation of thermally amendable and self-healing polymeric materials having reactive furfuryl functionality. In this case, the DA and retro-DA (rDA) reactions were carried out between the tailor-made homo- and copolymer of furfuryl methacrylate prepared by atom-transfer radical polymerization and a bismaleimide (BM). The kinetic studies of DA and rDA reactions were carried out using Fourier transform infrared spectroscopy. The DA polymers were insoluble in toluene at room temperature. When the DA polymers were heated at 100 degrees C in toluene, it was soluble. This is because of the cleavage between furfuryl functionality and BM. The chemical cross-link density was determined by the Flory-Rehner equation. The cross-linked polymer showed much greater adhesive strength at room temperature, but the adhesive strength was quite low at higher temperature. The self-healing capability was studied by using scanning electron microscopy analysis. The thermal and dynamic mechanical properties of the thermally amendable cross-linked materials were investigated by thermogravimetric analysis and dynamic mechanical analysis. PMID- 20355946 TI - Halloysite tubes as nanocontainers for anticorrosion coating with benzotriazole. AB - Halloysite clay nanotubes were investigated as a tubular container for the corrosion inhibitor benzotriazole. Halloysite is a naturally occurring cylindrical clay mineral with an internal diameter in the nanometer range and a length up to several micrometers, yielding a high-aspect-ratio hollow tube structure. Halloysite may be used as an additive in paints to produce a functional composite coating material. A maximum benzotriazole loading of 5% by weight was achieved for clay tubes of 50 nm external diameters and lumen of 15 nm. Variable release rates of the corrosion inhibitor were possible in a range between 5 and 100 h, as was demonstrated by formation of stoppers at tube openings. The anticorrosive performance of the sol-gel coating and paint loaded with 2-5% of halloysite-entrapped benzotriazole was tested on copper and on 2024 aluminum alloy by direct exposure of the metal plates to corrosive media. Kinetics of the corrosion spot formation at the coating defects was analyzed by the scanning vibrating electrode technique, and an essential damping of corrosion development was demonstrated for halloysite-loaded samples. PMID- 20355947 TI - Grain-size-dependent diamond-nondiamond composite films: characterization and field-emission properties. AB - Diamond films with grain sizes in the range of 5-1000 nm and grain boundaries containing nondiamond carbon are deposited on a silicon substrate by varying the deposition parameters. The overall morphologies of the as-deposited diamond nondiamond composite films are examined by scanning electron microscopy and atomic force microscopy, which show a decrease in the surface roughness with a decrease in the diamond grain size. Although the Raman spectra show predominately nondiamond carbon features in the diamond films with smaller grain sizes, glancing-angle X-ray diffraction spectra show the absence of graphitic carbon features and the presence of very small amorphous carbon diffraction features. The CH4 percentage (%) in Ar and H2 plasma during deposition plays a crucial role in the formation of diamond films with different grain sizes and nondiamond carbon contents, which, in turn, determines the field-emission behavior of the corresponding diamond films. The smaller the grain size of the diamond, the lower is the turn-on field for electron emission. A lower turn-on field is obtained from the diamond films deposited with 2-5% CH4 than from the films deposited with either 1% or 7.5% CH4 in the Ar medium. A current density greater than 1 mA/cm2 (at 50 V/microm) is obtained from diamond films deposited with a higher percentage of CH4. A model is suggested for the field-emission mechanism from the diamond-nondiamond composite films with different diamond grain sizes and nondiamond contents. PMID- 20355948 TI - Effect of annealing on the properties of indium-tin-oxynitride films as ohmic contacts for gan-based optoelectronic devices. AB - Indium-tin-oxynitride (ITON) films have been fabricated by rf sputtering from an indium-tin-oxide target in nitrogen plasma. The influence of postdeposition annealing up to 800 degrees C is analyzed by electrical, optical, and surface characterization of the films in comparison to indium-tin-oxide (ITO) films fabricated in argon plasma. High-temperature annealing resulted in ITO(N) films with similar carrier concentrations. However, the resistivity and optical transmittance of the ITON films were higher than those of the ITO films. Photoelectron spectroscopy revealed that nitrogen is incorporated into the ITON structure in an unbound state as well as through the formation of metal-nitrogen and oxynitride bonds that decorate oxygen vacancies. When the core level electron spectra of ITO and ITON films are compared, a correlation between carrier concentration and the incorporated nitrogen is found. Changes in ITON electrical properties are mainly induced by the release of nitrogen at temperatures above 550 degrees C. In this context, ohmic contact behavior was achieved for ITON on p type GaN after annealing at 600 degrees C, while no ohmic contact could be realized using ITO. PMID- 20355949 TI - Single-stage synthesis and characterization of reflective and conductive silver polyimide films prepared from silver(I) complexes with ODPA/4,4'-ODA. AB - Reflective and surface conductive polyimide films were prepared by the incorporation of silver(I) acetate and trifluoroacetylacetone into a dimethylacetamide solution of the poly(amic acid) formed 3,3',4,4'-oxidiphthalic dianhydride (ODPA) and 4,4'-oxidianiline (4,4'-ODA). Thermal curing of (trifluoroacetylacetonato)silver(I)-poly(amic acid) films led to cycloimidization with concomitant silver(I) reduction, which yielded a reflective and conductive silver surface at selected silver concentrations if the film was cured to a final temperature of 300 degrees C for several hours. The metallized ODPA/4,4'-ODA films retain the essential mechanical properties of an undoped film and have good thermal stability, particularly under a nitrogen atmosphere. The bulk of the composite film was not electrically conductive. The use of (hexafluoroacetylacetonato)silver(I) and silver(I) tetrafluoroborate as sources of silver(I) with ODPA/4,4'-ODA yielded modestly reflective films that never developed conductivity. The silvered films prepared with (trifluoroacetylacetonato)silver(I) can be patterned using mask-etch techniques. Comparisons are made among four similar silver-polyimide systems, with the polyimides being ODPA/4,4'-ODA, BTDA/4,4'-ODA, BPDA/4,4'-ODA, and 6FDA/4-BDAF. PMID- 20355950 TI - Hole transport in Poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] and high efficiency polymer solar cells from its blends with PCBM. AB - We report herein a detailed study of the thermal and hole-transport properties of poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] (F6T2) and its photovoltaic performance in a bulk-heterojunction (BHJ) solar cell. This crystalline polymer has a high weight-average molecular weight (M(w) = 52 400) with a polydispersity index of 1.99. With a band gap of 2.36 eV, F6T2 exhibits strong absorption in the 300-500 nm region. BHJ solar cells blending F6T2 with [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) (1:3 weight ratio) as the active layer present a high open-circuit voltage (V(oc) approximately 0.9 V) and a promising power conversion efficiency of 2.4% under simulated solar light AM1.5G (100 mW/cm(2)). Furthermore, F6T2 shows sufficient hole mobility [ca. 8.4 x 10(-5) cm(2)/(V s) at 310 K and 2.5 x 10(5) V/cm applied electric field] by a time-of-flight transient photocurrent technique, allowing efficient charge extraction and a good fill factor for solar cell application. Nanoscale phase separation was observed in F6T2/PCBM films with a surface roughness lower than 60 nm. PMID- 20355952 TI - Interplay of sequence, conformation, and binding at the Peptide-titania interface as mediated by water. AB - The initial stages of the adsorption of a hexapeptide at the aqueous titania interface are modeled using atomistic molecular dynamics simulations. This hexapeptide has been identified by experiment [Sano, K. I.; Shiba, K. J. Am. Chem. Soc. 2003, 125, 14234] to bind to Ti particles. We explore the current hypothesis presented by these authors that binding at this peptide-titania interface is the result of electrostatic interactions and find that contact with the surface appears to take place via a pair of oppositely charged groups in the peptide. Our data indicate that the peptide may initially recognize the water layers at the interface, not the titania surface itself, via these charged groups. We also report results of simulations for hexapeptide sequences with selected single-point mutations for alanine and compare these behaviors with those suggested from observed binding affinities from existing alanine scan experiments. Our results indicate that factors in addition to electrostatics also contribute, with the structural rigidity conferred by proline suggested to play a significant role. Finally, our findings suggest that intrapeptide interaction may provide mechanisms for surface detachment that could be detrimental to binding at the interface. PMID- 20355951 TI - Near-infrared phosphorescent polymeric nanomicelles: efficient optical probes for tumor imaging and detection. AB - We report a formulation of near-infrared (near-IR) phosphorescent polymeric nanomicelles and their use for in vivo high-contrast optical imaging, targeting, and detection of tumors in small animals. Near-IR phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin (Pt(TPNP)) were found to maintain their near-IR phosphorescence properties when encapsulated into phospholipid nanomicelles. The prepared phosphorescent micelles are of approximately 100 nm size and are highly stable in aqueous suspensions. A large spectral separation between the Pt(TPNP) absorption, with a peak at approximately 700 nm, and its phosphorescence emission, with a peak at approximately 900 nm, allows a dramatic decrease in the level of background autofluorescence and scattered excitation light in the near-IR spectral range, where the signal from the phosphorescent probe is observed. In vivo animal imaging with subcutaneously xenografted tumor bearing mice has resulted in high contrast optical images, indicating highly specific accumulation of the phosphorescent micelles into tumors. Using optical imaging with near-IR phosphorescent nanomicelles, detection of smaller, visually undetectable tumors has also been demonstrated. PMID- 20355953 TI - Double stimuli-responsive ultrafiltration membranes from polystyrene-block poly(N,N-dimethylaminoethyl methacrylate) diblock copolymers. AB - We report on the formation of self-supporting, double stimuli-responsive ultrafiltration membranes via the non-solvent-induced phase separation (NIPS) process. The polymers, polystyrene-block-poly(N,N-dimethylaminoethyl methacrylate) (PS-b-PDMAEMA), were synthesized via living anionic polymerization in THF using sec-butyllithium as initiator. Two amphiphilic diblock copolymers were used, S(81)D(19)(75) and S(68)D(32)(100). The membranes were cast from mixtures of THF and DMF. The influence of the solvent composition, the "open time" before immersion into the coagulation bath, and the casting film thickness onto the membrane morphology were thoroughly investigated, and flux values obtained for the different membrane systems were compared. The higher content in hydrophilic polymer for S(68)D(32)(100) resulted in a better compatibility with the nonsolvent bath consisting of water, leading to a slower precipitation and thus an improved control of the phase separation occurring. Under certain conditions, ordered microphase-separated porous morphologies were observed in parts of the membrane cross-section. Further, the "smart" properties of those novel materials are shown for two representative systems. It could be demonstrated that both stimuli for PDMAEMA, pH and temperature, can be reversibly and independently applied in order to significantly change the transmembrane water flux. PMID- 20355954 TI - Structural characterization combined with the first principles simulations of barium/strontium cobaltite/ferrite as promising material for solid oxide fuel cells cathodes and high-temperature oxygen permeation membranes. AB - Mixed ionic-electronic conducting perovskite type oxides with a general formula ABO(3) (where A = Ba, Sr, Ca and B = Co, Fe, Mn) often have high mobility of the oxygen vacancies and exhibit strong ionic conductivity. They are key materials that find use in several energy related applications, including solid oxide fuel cell (SOFC), sensors, oxygen separation membranes, and catalysts. Barium/strontium cobaltite/ferrite (BSCF) Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-delta) was recently identified as a promising candidate for cathode material in intermediate temperature SOFCs. In this work, we perform experimental and theoretical study of the local atomic structure of BSFC. Micro-Raman spectroscopy was performed to characterize the vibrational properties of BSCF. The Jahn-Teller distortion of octahedral coordination around Co(4+) cations was observed experimentally and explained theoretically. Different cations and oxygen vacancies ordering are examined using plane wave pseudopotential density functional theory. We find that cations are completely disordered, whereas oxygen vacancies exhibit a strong trend for aggregation in L-shaped trimer and square tetramer structure. On the basis of our results, we suggest a new explanation for BSCF phase stability. Instead of linear vacancy ordering, which must take place before the phase transition into brownmillerite structure, the oxygen vacancies in BSCF prefer to form the finite clusters and preserve the disordered cubic structure. This structural feature could be found only in the first-principles simulations and can not be explained by the effect of the ionic radii alone. PMID- 20355955 TI - A new approach for hydroxyapatite coating on polymeric materials using laser induced precursor formation and subsequent aging. AB - A new process, laser-induced precursor formation and subsequent aging in a supersaturated calcium phosphate aqueous solution (CP solution), was applied for coating a hydroxyapatite (HAP) film on a polymeric material, ethylene-vinyl alcohol copolymer (EVOH). Laser irradiation onto EVOH immersed in the CP solution induced the formation of CP precursors, and an HAP film composed of a submicrometer-scale cavernous structure was formed by subsequent aging in a CP solution without laser irradiation. The resulting HAP film coated on EVOH demonstrated excellent structural and chemical uniformity and cell adhesion with the CHO-K1 and BHK-21 cells. This process provides a practical technique for coating HAP onto polymeric materials. PMID- 20355956 TI - Patterned poly(2-hydroxyethyl methacrylate) brushes on silicon surfaces behave as "tentacles" to capture ferritin from aqueous solution. AB - We have used a very large scale integration process to generate well-defined patterns of polymerized 2-hydroxyethyl methacrylate (HEMA) on patterned Si(100) surfaces. An atom transfer radical polymerization initiator covalently bonded to the patterned surface was employed for the graft polymerization of HEMA to prepare the poly(2-hydroxyethyl methacrylate) (PHEMA) brushes. After immersing wafers presenting lines of these polymers in water and cyclohexane, we observed brush- and mushroom-like regions, respectively, for the PHEMA brushes, with various pattern resolutions. The PHEMA brushes behaved as "tentacles" that captured ferritin complexes from aqueous solution through entanglement between the brushes and the ferritin proteins, whose ferritins were trapped due to the collapsing of the PHEMA. Using high-resolution scanning electron microscopy, we observed patterned ferritin iron cores on the Si surface after thermal removal of the patterned PHEMA brushes and ferritin protein sheaths. PMID- 20355957 TI - Selective detection of trace Cr3+ in aqueous solution by using 5,5'-dithiobis (2 nitrobenzoic acid)-modified gold nanoparticles. AB - A simply prepared gold nanoparticle-based sensor, 5,5'-dithiobis (2-nitrobenzoic acid) (DTNBA)-modified gold nanoparticles, was prepared to explore the sensitive and selective detection of metal ions using a colorimetric technique. The selective detection of trace levels (93.6 ppb) Cr3+ in aqueous solution was achieved over 15 other metal ions. The functionalized gold nanoparticles became aggregated in solution in the presence of Cr3+ by an ion-templated chelation process, which caused an easily measurable change in the extinction spectrum of the particles and provided an inherently sensitive method for Cr3+ detection in aqueous solution. PMID- 20355958 TI - Outgassing of oxygen from polycarbonate. AB - A manometric permeation apparatus was used to study the "outgassing" or desorption of oxygen from polycarbonate (PC). A PC film was placed in the apparatus. Both sides were exposed to oxygen until the film was saturated. To simulate inert gas purging of a closed container or "microenvironment", oxygen was pumped from one side of the apparatus to reduce the concentration on that side to nearly zero. Oxygen concentrations on the freshly purged side rose quickly at first but then slowed. Eventually, a steady state was established and oxygen concentrations increased linearly with time. Mass-transport coefficients (permeation, diffusion, and solubility coefficients) were also estimated and then used to successfully predict the postpurge rise of the oxygen concentration. PMID- 20355959 TI - Molecular aggregation state and photovoltaic properties of chlorophyll-doped conducting poly(3-hexylthiophene)/MCM-41 nanocomposites. AB - Chlorophyll (Chl) was immobilized into a 1,4-butanediol-modified MCM-41 (BMCM-41) intercalated by poly(3-hexylthiophene) (P3HT) to form BMCM-41/P3HT/Chl nanocomposites having P3HT contents of 10, 30, 60, and 90 wt % from a solution casting method. Wide-angle X-ray diffraction and transmission electron microscopy studies indicate that the pore structure of MCM-41 was retained after surface modification and a subsequent P3HT intercalation process. Scanning electron microscopy images showed that the BMCM-41 nanoparticles dispersed into the polymer matrix of BMCM-41/P3HT/Chl, and the sample with 10 wt % P3HT content gives the most homogeneous nanoparticle dispersion. Nitrogen adsorption desorption results confirmed that the P3HT intercalation and Chl immobilization inside the BMCM-41 mesopore were successfully carried out. The pore volume and surface area of BMCM-41 decreased significantly when the amount of P3HT was increased from 10 to 90 wt %. The UV-vis study showed a blue shift of the pi-pi* transition band of P3HT in the spectra of BMCM-41/P3HT/Chl nanocomposites. The FT IR study indicates an increase of the thiophene ring stretching and a decrease of the C horizontal lineO stretching when P3HT and Chl were inside the mesopore. The photovoltaic property of Chl-doped P3HT was improved significantly upon the addition of BMCM-41 nanoparticles, and BMCM-41/P3HT-10/Chl exhibits the highest incident photon-to-current conversion efficiency of 7.16%. PMID- 20355961 TI - Microscale polymer-nanotube composites. AB - Polymer colloids with an interfacial coating of purified single-wall carbon nanotubes (SWCNTs) are synthesized from length- and type-sorted SWCNTs. Aqueous nanotube suspensions sorted through density-gradient ultracentrifugation are used to emulsify spherical polymer colloids of microscale dimensions that are characterized through a combination of optical microscopy, transmission electron microscopy, and impedance spectroscopy. The SWCNT-polymer composite particles exhibit electrical conductivities comparable to or better than those of bulk SWCNT-polymer composites at nanotube loadings of more than 1 order of magnitude lower. The composite particles retain the unique electronic and optical characteristics of the parent SWCNT solution with potential applications as microelectronic and microoptical components. PMID- 20355960 TI - Hybrid antimicrobial enzyme and silver nanoparticle coatings for medical instruments. AB - We report a method for the synthesis of antimicrobial coatings on medical instruments that combines the bacteriolytic activity of lysozyme and the biocidal properties of silver nanoparticles. Colloidal suspensions of lysozyme and silver nanoparticles were electrophoretically deposited onto the surface of stainless steel surgical blades and needles. Electrodeposited films firmly adhered to stainless steel surfaces even after extensive washing and retained the hydrolytic properties of lysozyme. The antimicrobial efficacy of coatings was tested by using blades and needles in an in vitro lytic assay designed to mimic the normal application of the instruments. Coated blades and needles were used to make incisions and punctures, respectively, into agarose infused with bacterial cells. Cell lysis was seen at the contact sites, demonstrating that antimicrobial activity is transferred into the media, as well as retained on the surface of the blades and needles. Blade coatings also exhibited antimicrobial activity against a range of bacterial species. In particular, coated blades demonstrated potent bactericidal activity, reducing cell viability by at least 3 log within 1.5 h for Klebsiella pneumoniae, Bacillus anthracis Sterne, and Bacillus subtilis and within 3 h for Staphylococcus aureus and Acinetobacter baylyi. The results confirmed that complex antimicrobial coatings can be created using facile methods for silver nanoparticle synthesis and electrodeposition. PMID- 20355962 TI - Fabrication of poly(3-hexylthiophene) thin films by vapor-phase polymerization for optoelectronic device applications. AB - The vapor-phase polymerization (VPP) of poly(3-hexylthiophene) (P3HT) was achieved successfully as an alternative method to conventional solution-based thin film fabrication. Using Fe(III)Cl(3).6H(2)O, a spontaneous reaction of 3 hexylthiophene monomers resulted in the rapid formation of conducting P3HT thin films directly on substrates, such as glass, indium-tin-oxide, and poly(ethylene terephthalate), at thicknesses ranging from 50 to 1000 nm. The VPP of P3HT was achieved using ferric chloride hexahydrate and a 1:1 ratio of a methanol/ethanol mixture as the solvent system. The developed VPP technique can provide good processing consistency with an electrical conductivity, a transmittance, and a surface roughness of approximately 10(-2) S/cm, >90%, and <10 nm, respectively. PMID- 20355963 TI - Alkali etching of a poly(lactide) fiber. AB - Alkali etching of a poly(l-lactic acid) fiber was studied by exposing the fiber surface to sodium hydroxide solutions. The factors examined included the etching time (0-1.5 h), alkali concentration (0.25-3 mol/L), and etching temperature (25 80 degrees C). The extent of etching was determined gravimetrically. Both weight loss and mechanical testing results suggest that alkali etching is strictly a surface hydrolysis reaction, as opposed to a bulk reaction, and thus the weight loss rate decreases with a shrinking fiber radius. A slight increase in the fiber crystallinity observed from thermal analysis was interpreted as a result of surface-limited etching on a sheath-core fiber microstructure. The dependence of the rate on the alkali concentration is nonlinear, suggesting that the fiber weight loss rate is subject to both chemical hydrolysis and transport limitations. The dependence of the rate on the temperature follows the Arrhenius equation. The fiber weight after etching can thus be predicted by an overall expression combining all factors: time, temperature, concentration, and fiber diameter. PMID- 20355964 TI - Novel long-term immobilization method for radioactive iodine-129 using a zeolite/apatite composite sintered body. AB - The amount of radioactive iodine generated from nuclear power plants is expected to increase with the proliferation of nuclear energy production, and long-term immobilization methods for such radioactive elements need to be developed to make nuclear energy sustainable. The standard immobilization method of radioactive elements, vitrification, is not very effective for radioactive iodine-129 because of the low solubility of iodine in silicate melts, its very high volatility at standard vitrification process temperatures, and its instability in the alkaline environment of deep geological layers below 300 m. We have developed a novel three-phase ceramic composite produced by a sintering process. Iodine adsorbed onto Ca-type zeolite A was covered with a hydroxyapatite nanolayer through the exchange reaction of ammonium with calcium. Clusters of iodine of 30 nm within the zeolite structure were found to be thermally stable up to 1253 K because of the partial blockage of the alpha-cage apertures by ammonium ions and the partial change from a crystalline phase to an amorphous phase at 473 K. No gasification of iodine molecules was found to occur during the sintering process. The outer phase was highly crystalline hydroxyfluorapatite in which the hydroxyapatite nanolayer plays an important role for successful sintering. The elution of iodine in low-dioxygen water, similar to that found within the Earth's crust, was investigated and was found to occur only in the surface layer of the sintered body. PMID- 20355965 TI - Highly condensed epoxy-oligosiloxane-based hybrid material for transparent low-k dielectric coatings. AB - A highly condensed epoxy-oligosiloxane resin was synthesized using a sol-gel condensation reaction of (3-glycidoxypropyl)trimethoxysilane and diphenylsilanediol in the presence of solvent. A higher degree of condensation and a larger molecular size of oligosiloxanes were achieved compared to a condensation reaction without the addition of a solvent. The epoxy-hybrimer coating film was fabricated by the spin coating and thermal curing of the synthesized oligosiloxane resin. The leakage current density and the dielectric constant decreased from 25.9 to 7.6 nA cm(-2) and from 3.16 to 3.03, respectively, by using the solvent in the preparation. The hybrimer coating film of a highly condensed oligosiloxane resin had a high transmittance of over 90% in a wavelength between 300 and 800 nm. Thus, the epoxy-hybrimer coating film can be utilized as the passivation layer in the thin-film transistor. PMID- 20355966 TI - Fabrication and testing of a microneedles sensor array for p-cresol detection with potential biofuel applications. AB - We present a miniaturized high-throughput sensor array that will augment biofuel technology by facilitating in situ biochemical measurements upon micrometer-scale surfaces of leaves, stems, or petals. We used semiconductor processing to photopattern Foturan glass wafers and fabricated gold-plated microscopic electrode needles (ElectroNeedles) that pierced 125-mum-thick surfaces without deformation. The 5 x 5 or 10 x 10 arrays of ElectroNeedles can analyze 25 or 100 samples simultaneously, increasing throughput. Each microneedle in the array can also be individually addressed and selectively functionalized using diazonium electrodeposition, conferring multiplexing capability. Our microfabrication is a simple, inexpensive, and rapid alternative to the time-, cost-, and protocol intense, deep-reactive-ion-etching Bosch process. We validated the system performance by electrochemically detecting p-cresol, a phenolic substrate for laccase, an enzyme that is implicated in lignin degradation and therefore important to biofuels. Our limits of detection (LOD) and quantization (LOQ) for p cresol were 1.8 and 16microM, respectively, rivaling fluorescence detection (LOD and LOQ = 0.4 and 3microM, respectively). ElectroNeedles are multiplexed, high throughput, chip-based sensor arrays designed for minimally invasive penetration of plant surfaces, enabling in situ and point-of-test analyses of biofuel-related biochemicals. PMID- 20355967 TI - Functionalized polypyrrole film: synthesis, characterization, and potential applications in chemical and biological sensors. AB - In this paper, we report the synthesis of a carboxyl-functionalized polypyrrole derivative, a poly(pyrrole-N-propanoic acid) (PPPA) film, by electrochemical polymerization, and the investigation of its basic properties via traditional characterization techniques such as confocal-Raman, FTIR, SEM, AFM, UV-vis, fluorescence microscopy, and contact-angle measurements. The experimental data show that the as-prepared PPPA film exhibits a hydrophilic nanoporous structure, abundant -COOH functional groups in the polymer backbone, and high fluorescent emission under laser excitation. On the basis of these unique properties, further experiments were conducted to demonstrate three potential applications of the PPPA film in chemical and biological sensors: a permeable and permselective membrane, a membrane with specific recognition sites for biomolecule immobilization, and a fluorescent conjugated polymer for amplification of fluorescence quenching. Specifically, the permeability and permselectivity of ion species through the PPPA film are detected by means of rotating-disk-electrode voltammetry; the specific recognition sites on the film surface are confirmed with protein immobilization, and the amplification of fluorescence quenching is measured by the addition of a quenching agent with fluorescence microscopy. The results are in good agreement with our expectations. PMID- 20355968 TI - Fabrication of supported mesoporous TiO2 membranes: matching the assembled and interparticle pores for an improved ultrafiltration performance. AB - We report the fabrication and ultrafiltration performances of an asymmetric composite membrane with a mesoporous TiO2 skin layer coated on a macroporous alumina support. Mesoporous TiO2 was first prepared and deposited on the substrate through a sol-gel process where a ethylene oxide and propylene oxide triblock polymer (PEO-PPO-PEO, P123) was used to modify the properties of the sols and also to introduce assembled pores in the skin layer. The obtained mesoporous TiO2 membrane was characterized by means of scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and nitrogen adsorption. We found that there were two types of wormlike mesopores present in the TiO2 membrane: interparticle and assembled pores. By carefully controlling the sol properties, we made the two types of pores match each other, which means the size of the interparticle pores is close or smaller than that of the assembled pores. This pore-size matching ensures a narrow pore-size distribution and, consequently, a good retention performance of the obtained TiO2 membrane. The pore size of the TiO2 membrane is ca. 6 nm, as revealed by both nitrogen adsorption and dextran separation experiments, and it has a pure water flux of 7.12 L/(m(2) x h x bar) and a cutoff molecular weight of 19 000 Da, which is very attractive for applications in the enrichment and separation of proteins and polypeptides. PMID- 20355969 TI - Conjugated polymers based on benzo[2,1-b:3,4-b']dithiophene with low-lying highest occupied molecular orbital energy levels for organic photovoltaics. AB - Fusing bithiophene units with a benzo moiety, benzo[2,1-b:3,4-b']dithiophene (BDT), was projected by theoretical calculations to lower the highest occupied molecular orbital (HOMO) energy level of the resulting polymers compared with that of the bithiophene unit, which would enhance the open circuit voltage of bulk heterojunction photovoltaic cells fabricated from BDT-based polymers blended with PCBM. The homopolymer of BDT (HMPBDT) and alternating copolymer of BDT with 2,1,3-benzothiadiazole (PBDT-BT) were therefore synthesized and fully characterized. Both the homopolymer (HMPBDT) and the copolymer (PBDT-BT) were experimentally confirmed to have low HOMO energy levels (-5.70 eV for HMPBDT and 5.34 eV for PBDT-BT). Introducing the acceptor moiety (2,1,3-benzothiadiazole) successfully lowered the optical band gap of the copolymer from 2.31 eV (HMPBDT) to 1.78 eV (PBDT-BT). Bulk heterojunction photovoltaic devices were fabricated from blends of these structurally related polymers with PBCM to investigate the photovoltaic performances. The optimized device of HMPBDT:PCBM (1:3, 180 nm) exhibited an improved open circuit voltage (V(oc)) of 0.76 V, a short circuit current (J(sc)) of 0.34 mA/cm(2), and a fill factor (FF) of 0.40, offering an overall efficiency of 0.10%. The observed large phase separation of the thin film by AFM and the large band gap were accountable for the small current. The optimized device of PBDT-BT:PCBM (1:3, 55 nm) demonstrated a better efficiency of 0.6%, with V(oc) = 0.72 V, J(sc) = 2.06 mA/cm(2), and FF = 0.42. The much improved current was attributed to the lower bandgap and better film morphology. However, the low hole mobility limited the thickness of the PBDT-BT:PCBM film, making inaccessible the thicker film which would utilize more light and enhance the current. Further improvements are expected if the mobility and film morphology can be improved by the new materials design, together with low band gap and low HOMO energy level. PMID- 20355970 TI - Focused-ion-beam-assisted magnet fabrication and manipulation for magnetic field detection applications. AB - A focused-ion-beam-assisted technique intended for ultrasmall, hard-magnet fabrication has been developed. By means of ion-beam-induced milling and deposition, reduced-size NdFeB magnets were extracted from a macroscopic quarry and bonded to the surface of a thin-film bulk acoustic resonator (FBAR). Electrical characterization of the FBAR before and after bonding of the magnet was carried out, thus observing both a downshifting of the resonance frequency and a reduction of the quality factor of the resonator. The magnetic behavior of the nanomagnet has been confirmed by means of magnetometry measurements based on atomic force microscopy. PMID- 20355971 TI - Stimuli-responsive hydrogel membranes coupled with biocatalytic processes. AB - A nanostructured signal-responsive thin hydrogel membrane was coupled with enzyme based systems to yield "smart" multisignal-responsive hybrid systems with built in "logic". The enzyme systems transduce biochemical input signals into structural changes of the membrane, thus resulting in the amplification of the biochemical signals and their transformation into the gated transport of molecules through the membrane. Coupling of the biocatalytic systems with a stimuli-responsive membrane is a promising approach for the development of materials that can regulate transport and release of chemicals/drugs by receiving and processing the biochemical information via biochemical reactions. PMID- 20355972 TI - Self-initiated surface graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on poly(ether ether ketone) by photoirradiation. AB - In the present paper, we reported the fabrication of a highly hydrophilic nanometer-scale modified surface on a poly(ether ether ketone) (PEEK) substrate by photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) in the absence of photoinitiators. Photoirradiation results in the generation of semibenzopinacol-containing radicals of benzophenone units in the PEEK molecular structure, which acts as a photoinitiator during graft polymerization. The poly(MPC)-grafted PEEK surface fabricated by a novel and simple polymerization system exhibited unique characteristics such as high wettability and high antiprotein adsorption, which makes it highly suitable for medical applications. PMID- 20355973 TI - Modulation of cell adhesion complexes by surface protein patterns. AB - Cell adhesion is an important process in several biological phenomena. To investigate the formation and organization of focal adhesions, we developed a patterning approach based on electron beam lithography. Nanodots (radius <1230 nm) and nanorings (inner radius <320 nm) of fibronectin (FN) were patterned on a K-Casein background. Intracellular vinculin immunofluorescence mirrored the FN nanopatterns. Atomic force microscopy showed that FN nanodots and nanorings organize the immediate cytoskeleton into straight fibrils and diverging fibril bundles, respectively. Our results suggest that a minimum of approximately 40 FN molecules is required for a cell to form a focal adhesion. PMID- 20355974 TI - Fabrication of highly ordered arrays of platinum nanoparticles using direct laser interference patterning. AB - Highly ordered electrode arrays composed of lines of platinum nanoparticles deposited onto gold substrates have been made by direct laser interference patterning of polyaniline thin films, followed by electrochemical deposition of platinum nanoparticles. Nanostructured arrays of electrocatalytic platinum particles are built in that way. PMID- 20355975 TI - The effect of synthesis conditions and humidity on current-voltage relations in electrodeposited ZnO-based Schottky junctions. AB - Electrochemically produced ZnO/metal rectifying (Schottky) junctions can exhibit consistent barrier heights and high rectifying ratios when prepared using optimized electrolyte pH (6.5) and applied voltage (100 degrees C. Fracture toughness (as K(1c)) of the epoxy thermosets cured with relatively flexible amines such as ethylenediamine (EDA), diethylenetriamine (DETA), and m-xylylenediamine (MXDA) reaches near its full cure value at only approximately 65-70% conversion. The maximum in K(1c) for these types of epoxy thermosets is at approximately 90% conversion for EDA and DETA but just below its full cure for MXDA. Isophoronediamine represents a special case for fracture behavior because of its apparent substantial cyclization during cure. In the 4,4' diaminodiphenylsulfone series, K(1c) generally increases with conversion as the concentrations of their strongly antiplasticizing soluble and pendant fractions decrease. A uniform trend of decreasing tensile modulus with increasing conversion was observed in each formulation and is consistent with the expected decrease in the cohesive energy density as monomer glass is transformed into polymer glass. PMID- 20356019 TI - Processing and characterization of ultrathin carbon coatings on glass. AB - Ultrathin carbon layers, on the order of 3-6 nm in thickness, were formed on glass substrates by spin coating and pyrolysis of polymer precursors. The organic precursors used were poly(furfuryl alcohol), coal tar pitch, and a photoresist. The carbon coatings were characterized by ellipsometry, optical profilometry, water contact angle, confocal Raman spectroscopy, UV-vis spectroscopy, and atomic force microscopy. We also report the transparency, hydrophobicity, friction, weathering resistance, and electrical conductivity of the carbon-coated glass. The results reveal that up to 97% transparent, ultrathin carbon films could be formed on glass substrates with a root-mean-square roughness of less than approximately 0.3 nm. This carbon layer modified the otherwise hydrophilic surface of the glass to yield a water contact angle of 85 degrees . The coatings were also found to provide a water barrier against weathering under hot and humid conditions. A 4.5-nm-thick carbon film on glass had a sheet resistance of 55.6 kOmega m and a conductivity of 40 S/cm. PMID- 20356020 TI - Comparison of CH, C3, CHF, and CF2 surface reactivities during plasma-enhanced chemical vapor deposition of fluorocarbon films. AB - The overall character of films deposited using plasma-enhanced chemical vapor deposition relies on the interactions of gas-phase molecules with the depositing film surface. The steady-state surface interactions of CH, C3, CHF, and CF2 have been characterized at the interface of depositing fluorocarbon (FC) films using the imaging of radicals interacting with surfaces (IRIS) technique. IRIS measurements show that the relative gas-phase densities of CH, C3, CHF, and CF2 in mixed FC plasmas depend on the CH2F2/C3F8 ratio. Similar results are found using optical emission spectroscopy to monitor the production of excited-state plasma species. The effects of plasma parameters, such as the feed gas composition and substrate bias on the radical surface, were measured. Under all conditions, the surface reactivity for CH radicals is near unity, whereas those for C3, CHF, and CF2 exhibit very low surface reactivity but also show some dependence on experimental parameters. Under some conditions, CF2 and CHF are generated at the surface of the depositing film. Surface reactivity measurements indicate that CF2, CHF, and C3 may contribute to FC growth only when adsorbing at reactive sites at the film surface. Moreover, the low surface reactivities of singlet species such as C3, CF2, and CHF may be related to the electronic configuration of the molecules. PMID- 20356021 TI - Quasi-solid-state dye-sensitized solar cells with polymer gel electrolyte and triphenylamine-based organic dyes. AB - We report on the application of a poly(methyl acrylate)/poly(ethylene glycol) based polymer gel electrolyte and triphenylamine-based metal-free organic dyes in quasi-solid-state dye-sensitized solar cells. The poly(methyl acrylate)/poly(ethylene glycol) hybrid is beneficial to the entrapment of a large volume of liquid electrolyte. At 25 degrees C, the ionic conductivity and the triiodide ionic diffusion constant of the as-prepared polymer gel electrolyte are 2.1 mS cm(-1) and 2.3 x 10(-6) cm(2) s(-1), respectively. The quasi-solid-state solar cell sensitized by triphenylamine-based dyes attains an overall energy conversion efficiency of 5.76% at a light intensity of 30 mW cm(-2). The presence of poly(ethylene glycol) in the electrolyte obviously increases the conductivity and energy conversion efficiency compared to that without poly(ethylene glycol). PMID- 20356022 TI - Polypyrrole actuator with a bioadhesive surface for accumulating bacteria from physiological media. AB - A gold/polypyrrole (Au/PPy) bilayer actuator was fabricated by electrochemical deposition, and its surface was modified with a bioadhesive polymer, polydopamine. The actuator exhibited high performances of actuation in physiological media. Furthermore, the surface of the actuator is sticky in water and thus can seize bacteria from their aqueous solutions. Actuation greatly increased the efficiency of adhering bacteria on the actuator surface, and this technique provides a cheap and convenient approach for accumulating bacteria from physiological media. PMID- 20356023 TI - Fabrication of size-controlled starch-based nanospheres by nanoprecipitation. AB - Nanometric and monodisperse starch acetate nanospheres can be prepared through a simple procedure of nanoprecipitation, by the dropwise addition of water to an acetone solution of starch acetate, without any stabilizing agent. This is the first report of the preparation of starch-based nanospheres by this method. The size of the nanospheres obtained can be easily controlled by a number of simple and efficient modifications, i.e., through regulation of the polymer concentration in acetone, the proportions of the water and organic phases, and the molecular weight and degree of substitution of the starch esters. A number of reasons are suggested to explain the observed transitions in the particle size. Fluorescence spectroscopic studies proved that these types of nanospheres could be potentially used for the encapsulation of hydrophobic drugs. PMID- 20356024 TI - Transfer-printing and host-guest properties of 3D supramolecular particle structures. AB - Mechanically robust and crystalline supramolecular particle structures have been constructed by decoupling nanoparticle assembly and supramolecular glue infiltration into a sequential process. First, beta-cyclodextrin (CD) functionalized polystyrene particles (d approximately 500 nm) were assembled on a CD-functionalized surface via convective assembly to form highly ordered, but mechanically unstable, particle crystals. Subsequently, the crystals were infiltrated by a solution of adamantyl-functionalized dendrimers, functioning as a supramolecular glue to bind neighboring particles together and to couple the entire particle crystal to the CD surface, both in a noncovalent manner. The supramolecular particle crystals are highly robust, as witnessed by their ability to withstand agitation by ultrasonication. When assembled on a poly(dimethylsiloxane) (PDMS) stamp, the dendrimer-infiltrated particle crystals could be transfer-printed onto a CD-functionalized target surface. By variation of the geometry and size of the PDMS stamps, single particle lines, interconnected particle rings, and V-shaped particle assemblies were obtained. The particle structures served as 3D receptors for the binding of (multiple) complementary guest molecules, indicating that the supramolecular host functionalities of the particle crystals were retained throughout the fabrication process. PMID- 20356025 TI - Nanostructures of octadecyltrisiloxane self-assembled monolayers produced on Au111 using particle lithography. AB - Preparing high-quality self-assembled monolayers (SAMs) of organosilanes on conductive metal substrates such as gold is problematic because of the hydrophobic nature of the surface under ambient conditions. Trace amounts of water are required for a surface hydrolysis reaction to form siloxane bridges to the metal substrate. We describe an approach using sequential steps of ultraviolet (UV) irradiation, particle lithography, and chemical vapor deposition of octadecyltrichlorosilane (OTS) to successfully prepare silane nanostructures on Au111 surfaces. Pretreatment of gold films with UV irradiation renders the surface to be sufficiently hydrophilic for particle lithography. Close-packed films of monodisperse latex mesospheres provide an evaporative mask to spatially direct the placement of nanoscopic amounts of water on surfaces. Vapor-phase organosilanes deposit selectively at areas of the surface containing water residues to produce millions of nanopatterns with regular thickness, geometry, and periodicity. Atomic force microscopy (AFM) images reveal that OTS binding is localized to areas defined by water residues. The spacing between adjacent nanopatterns is determined by the periodicity of the latex mask; however, the dimensions of the nanostructures are confined to a narrow contact area of the water meniscus, which surrounds the base of the latex spheres. The siloxane nanostructures on Au111 furnish an excellent model surface for AFM characterizations, as demonstrated with current-sensing measurements. PMID- 20356026 TI - Reaction pathways of 2-iodoacetic acid on Cu(100): coverage-dependent competition between C-I bond scission and COOH deprotonation and identification of surface intermediates. AB - The chemistry of 2-iodoacetic acid on Cu(100) has been studied by a combination of reflection-absorption infrared spectroscopy (RAIRS), X-ray photoelectron spectroscopy (XPS), temperature-programmed reaction/desorption (TPR/D), and theoretical calculations based on density functional theory for the optimized intermediate structures. In the thermal decomposition of ICH(2)COOH on Cu(100) with a coverage less than a half monolayer, three surface intermediates, CH(2)COO, CH(3)COO, and CCOH, are generated and characterized spectroscopically. Based on their different thermal stabilities, the reaction pathways of ICH(2)COOH on Cu(100) at temperatures higher than 230 K are established to be ICH(2)COOH --> CH(2)COO + H + I, CH(2)COO + H --> CH(3)COO, and CH(3)COO --> CCOH. Theoretical calculations suggest that the surface CH(2)COO has the skeletal plane, with delocalized pi electrons, approximately parallel to the surface. The calculated Mulliken charges agree with the detected binding energies for the two carbon atoms in CH(2)COO on Cu(100). The CCOH derived from CH(3)COO decomposition has a CC stretching frequency at 2025 cm(-1), reflecting its triple-bond character which is consistent with the calculated CCOH structure on Cu(100). Theoretically, CCOH at the bridge and hollow sites has a similar stability and is adsorbed with the molecular axis approximately perpendicular to the surface. The TPR/D study has shown the evolution of the products of H(2), CH(4), H(2)O, CO, CO(2), CH(2)CO, and CH(3)COOH from CH(3)COO decomposition between 500 and 600 K and the formation of H(2) and CO from CCOH between 600 and 700 K. However, at a coverage near one monolayer, the major species formed at 230 and 320 K are proposed to be ICH(2)COO and CH(3)COO. CH(3)COO becomes the only species present on the surface at 400 K. That is, there are two reaction pathways of ICH(2)COOH --> ICH(2)COO + H and ICH(2)COO + H --> CH(3)COO + I (possibly via CH(2)COO), which are different from those observed at lower coverages. Because the C-I bond dissociation of iodoethane on copper single crystal surfaces occurs at approximately 120 K and that the deprotonation of CH(3)COOH on Cu(100) occurs at approximately 220 K, the preferential COOH dehydrogenation of monolayer ICH(2)COOH is an interesting result, possibly due to electronic and/or steric effects. PMID- 20356027 TI - Solid-state 51V NMR investigation of the intercalation of alkylamines into layered alpha-vanadyl phosphate. AB - The intercalation behavior of layered alpha-phase vanadyl phosphate, alpha VOPO(4).2H(2)O (alpha-VP), with alkylamine was investigated by (51)V solid-state NMR in combination with powder XRD. The XRD results show that the amines form bimolecular layers upon intercalation. For the intercalation with short chain amines (propylamine, pentylamine, and hexylamine), the C-C chain of the amines is tilted with respect to the inorganic basal plane. The amines with a longer alkyl chain (dodecylamine and hexadecylamine) tend to adopt an orientation where the C C chain direction is perpendicular to the VP layer. For the amine with eight carbon atoms (octylamine), the intercalation results in two coexisting phases with different chain orientations. (51)V solid-state NMR was used to directly probe the effect of intercalation on the metal center environments. Both (51)V magic-angle spinning and static spectra of alpha-VP intercalated with different amines were obtained at different magnetic fields, and they are sensitive to intercalation. The intercalation induces the (51)V isotropic chemical shift to move toward deshielded direction. (51)V chemical shielding parameters such as the span are sensitive to the orientation of the amine chain with respect to the VP basal plane. For the V centers interacting with the amines having a tilted orientation, the (51)V span gradually decreases with increasing alkyl chain length. However, the span of the (51)V atoms interacting with the amines perpendicular to the VP layer is larger and independent of the length of the alkyl chain. The (51)V NMR data indicate that for the alpha-VPs intercalated with long-chain amines, such as dodecylamine and hexadecylamine, the amines can assume both tilted and perpendicular orientations. PMID- 20356028 TI - STM study of molecule double-rows in mixed self-assembled monolayers of alkanethiols. AB - Using scanning tunnelling microscopy (STM), we have studied mixed self-assembled monolayers of linear alkanethiol molecules. Nonanedithiol (C9S2), nonanethiol (C9S), decanethiol (C10S), and dodecanethiol (C12S) were inserted into a self assembled octanethiol (C8S) host matrix monolayer on an Au(111) surface using a two-step method. Quasi-one-dimensional double-row structures were found in the ordered, close-packed domains of the C8S matrix for each mixed monolayer system. These close-packed domains coexist with ordered striped phase domains (for C9S and C10S) or with a disordered phase (for C9S2 and C12S). Results from high resolution images suggest that the double-rows are composed of inserted non nearest-neighbor substitutional molecules, the ordering of which may be a result of locally induced surface stress. PMID- 20356029 TI - Effect of electrolyte and adsorbates on charging rates in mesoporous gold electrodes. AB - The classical model for porous electrodes reported by De Levie several decades ago (and expanded upon since then) was developed mainly to describe pores with micrometer-scale diameters. Presumably it will break down as pore diameters approach atomic dimensions. Mesoporous gold formed by dealloying is a valuable test platform for this because its 10 nm pores are on the boundary of this expected breakdown and because the electrochemical and surface properties of gold are relatively well understood. The De Levie model works for these electrodes at high salt concentrations, but under dilute conditions, there is not enough salt locally to charge the interface, increasing real impedance on intermediate time scales. Specific adsorption on pore walls can cause a similar increase and also cause an effective mobility decrease, tunable through electrolyte choice and the use of alkanethiol monolayers. These effects are not expected in micrometer-scale pores and are important considerations when designing devices with nanoporous electrodes. PMID- 20356030 TI - The structures of the C185S and C185A mutants of sulfite oxidase reveal rearrangement of the active site. AB - Sulfite oxidase (SO) catalyzes the physiologically critical conversion of sulfite to sulfate. Enzymatic activity is dependent on the presence of the metal molybdenum complexed with a pyranopterin-dithiolene cofactor termed molybdopterin. Comparison of the amino acid sequences of SOs from a variety of sources has identified a single conserved Cys residue essential for catalytic activity. The crystal structure of chicken liver sulfite oxidase indicated that this residue, Cys185 in chicken SO, coordinates the Mo atom in the active site. To improve our understanding of the role of this residue in the catalytic mechanism of sulfite oxidase, serine and alanine variants at position 185 of recombinant chicken SO were generated. Spectroscopic and kinetic studies indicate that neither variant is capable of sulfite oxidation. The crystal structure of the C185S variant was determined to 1.9 A resolution and to 2.4 A resolution in the presence of sulfite, and the C185A variant to 2.8 A resolution. The structures of the C185S and C185A variants revealed that neither the Ser or Ala side chains appeared to closely interact with the Mo atom and that a third oxo group replaced the usual cysteine sulfur ligand at the Mo center, confirming earlier extended X-ray absorption fine structure spectroscopy (EXAFS) work on the human C207S mutant. An unexpected result was that in the C185S variant, in the absence of sulfite, the active site residue Tyr322 became disordered as did the loop region flanking it. In the C185S variant crystallized in the presence of sulfite, the Tyr322 residue relocalized to the active site. The C185A variant structure also indicated the presence of a third oxygen ligand; however, Tyr322 remained in the active site. EXAFS studies of the Mo coordination environment indicate the Mo atom is in the oxidized Mo(VI) state in both the C185S and C185A variants of chicken SO and show the expected trioxodithiolene active site. Density functional theory calculations of the trioxo form of the cofactor reasonably reproducd the Mo horizontal lineO distances of the complex; however, the calculated Mo-S distances were slightly longer than either crystallographic or EXAFS measurements. Taken together, these results indicate that the active sites of the C185S and C185A variants are essentially catalytically inactive, the crystal structures of C185S and C185A variants contain a fully oxidized, trioxo form of the cofactor, and Tyr322 can undergo a conformational change that is relevant to the reaction mechanism. Additional DFT calculations demonstrated that such methods can reasonably reproduce the geometry and bond lengths of the active site. PMID- 20356031 TI - Methylene blue incorporation into alkanethiol SAMs on Au(111): effect of hydrocarbon chain ordering. AB - A detailed polarization modulation infrared reflection absorption spectroscopy, scanning tunneling microscopy, and electrochemical study on methylene blue (MB) incorporation into alkanethiolate self-assembled monolayers (SAMs) on Au(111) is reported. Results show that the amount of MB incorporated in the SAMs reaches a maximum for intermediate hydrocarbon chain lengths (C10-C12). Well-ordered SAMs of long alkanethiols (C > C12) hinder the incorporation of the MB molecules into the SAM. On the other hand, less ordered SAMs of short alkanethiols (C < or = C6) are not efficient to retain the MB incorporated through the defects. For C12 the amount of incorporated MB increases as the SAM disorder is increased. This information is essential to the design of efficient thiol-based Au vectors for transport and delivery of molecules as well as thiol-based Au devices for molecular sensing. PMID- 20356032 TI - Cation exchange on the surface of gold nanorods with a polymerizable surfactant: polymerization, stability, and toxicity evaluation. AB - Gold nanorods were synthesized using a seed-mediated wet chemical approach with a quaternary ammonium surfactant, cetyltrimethylammonium bromide (CTAB), that forms a bilayer on the surface of the nanorods. The CTAB molecules in the bilayer were exchanged with a similar polymerizable analog, 11-(acryloyloxy) undecyltrimethyl ammonium bromide (p-CTAB). Mass spectrometric analysis of the degree of exchange of CTAB for p-CTAB, after gold digestion, gave 77 +/- 3 and 23 +/- 1% for p-CTAB and CTAB, respectively. On-rod polymerization with a cationic free-radical initiator was confirmed by FTIR analysis and did not induce aggregation as judged by ultraviolet-visible spectroscopy, transmission electron microscopy, and dynamic light scattering measurements after polymerization. In contrast to the nanorods before polymerization, the nanorods with a polymerized bilayer showed improved stability against dialysis as well as enhanced biocompatibility as measured using a viability assay on cultured human cells. Our results indicate that (1) CTAB molecules on the surface of the gold nanorods are exchangeable with similar surfactants that have a positively charged headgroup and (2) surfactant polymerization on the surface of the gold nanorods enhances both the stability and biocompatibility of these nanomaterials, probably by decreasing the degree of surfactant desorption from the surface. PMID- 20356033 TI - Disruption of the steroid metabolome in fish caused by exposure to the environmental estrogen 17alpha-ethinylestradiol. AB - Exposure to environmental estrogens such as 17alpha-ethinylestradiol (EE2) has been associated with feminization and a decline in fertility of male fish. To investigate the effect of estrogen exposure on steroid homeostasis, we exposed roach (Rutilus rutilus) to EE2 (1-29 ng/L) for 18 days and analyzed steroid profiles in bile and plasma using targeted analyses and in liver and gonadal tissues using mass spectrometry metabolite profiling techniques (metabolomics). Exposure to EE2 resulted in a concentration dependent reduction of estrogens and androgens in bile and plasma of both male and female fish. At 10 ngEE2/L, significant reductions in concentrations of hydroxyprogesterone, androstenedione, 11-hydroxyandrostenedione, and 11-ketotestosterone were detected in the testes metabolome, indicating disruption of steroid biosynthesis upstream of androgen metabolism. Estrogen exposure also resulted in increased biosynthesis of cortisol and cortisone in testes and ovaries, respectively, but did not alter glucocorticoid concentrations in the liver or plasma. This first report on the effect of EE2 exposure on the steroid metabolome in fish tissues suggests that both sex steroid and glucocorticoid pathways are one of the primary targets of estrogen exposure in fish gonads and provides further insights into the mode of action of this endocrine disrupting chemical. PMID- 20356034 TI - Reduced trace element concentrations in fast-growing juvenile Atlantic salmon in natural streams. AB - To assess the effect of rapid individual growth on trace element concentrations in fish, we measured concentrations of seven trace elements (As, Cd, Cs, Hg, Pb, Se, Zn) in stream-dwelling Atlantic salmon (Salmo salar) from 15 sites encompassing a 10-fold range in salmon growth. All salmon were hatched under uniform conditions, released into streams, and sampled approximately 120 days later for trace element analysis. For most elements, element concentrations in salmon tracked those in their prey. Fast-growing salmon had lower concentrations of all elements than slow growers, after accounting for prey concentrations. This pattern held for essential and nonessential elements, as well as elements that accumulate from food and those that can accumulate from water. At the sites with the fastest salmon growth, trace element concentrations in salmon were 37% (Cs) to 86% (Pb) lower than at sites where growth was suppressed. Given that concentrations were generally below levels harmful to salmon and that the pattern was consistent across all elements, we suggest that dilution of elements in larger biomass led to lower concentrations in fast-growing fish. Streams that foster rapid, efficient fish growth may produce fish with lower concentrations of elements potentially toxic for human and wildlife consumers. PMID- 20356035 TI - Synthesis and characteristics of graphene oxide-derived carbon nanosheet-Pd nanosized particle composites. AB - Carbon nanosheet (CNS)-Pd nanosized particle (NP) composites were synthesized by using graphite oxide (GO) and bis(ethylenediamine)palladium(II) (Pd(en)(2)(2+)) as the precursors, and their structure and adsorption properties were examined. It was found that the Pd(en)(2)(2+) complex ions can be intercalated into GO layers highly efficiently to form a layered structure containing a large amount of Pd (approximately 12 wt %). By the subsequent chemical reduction, Pd NPs (2-6 nm in size) are well dispersed between CNS to form a CNS-Pd NP composite and serve as spacers to increase the porosity of the composite. Hydrogen adsorption results demonstrate that both Pd NPs and CNS play important roles in hydrogen adsorption, particularly at a lower temperature and for CNS with deficient sites, which bring about a H(2) adsorption greater than those on other Pd-loaded nanocarbon materials reported so far. The unique composite nanostructure having large contents of Pd NPs (20-25 wt %) stabilized by CNSs is hopeful to be applied to the fields of H(2)-related catalysis, sensing, and so forth. PMID- 20356036 TI - Ultrafast MAS solid-state NMR permits extensive 13C and 1H detection in paramagnetic metalloproteins. AB - We show here that by combining tailored approaches based on ultrafast (60 kHz) MAS on the Co(II)-replaced catalytic domain of matrix metalloproteinase 12 (CoMMP 12) we can observe and assign, in a highly paramagnetic protein in the solid state, (13)C and even (1)H resonances from the residues coordinating the metal center. In addition, by exploiting the enhanced relaxation caused by the paramagnetic center, and the low power irradiation enabled by the fast MAS, this can be achieved in remarkably short times and at very high field (21.2 T), with only less than 1 mg of sample. Furthermore, using the known crystal structure of the compound, we are able to distinguish and measure pseudocontact (PCS) contributions to the shifts up to the coordinating ligands and to unveil structural information. PMID- 20356037 TI - Inactivation of MS2 coliphage in Fenton and Fenton-like systems: role of transition metals, hydrogen peroxide and sunlight. AB - The inactivation of coliphage MS2 by iron- and copper-catalyzed Fenton systems was studied to assess the importance of this process for virus inactivation in natural systems and during water treatment by advanced oxidation processes. The influence of H(2)O(2) (3-50 microM) and metal (1-10 microM) concentrations, HO(*) production, and sunlight on inactivation was investigated. Inactivation was first order with respect to H(2)O(2), but the dependence on the metal concentration was more complex. In the Cu/H(2)O(2) system, the inactivation rate constant k(obs) increased with added Cu up to 2.5 microM, and then leveled off. This was consistent with Cu saturation of the solution, indicating that only soluble Cu contributed to inactivation. In contrast, inactivation in the Fe/H(2)O(2) system was governed by colloidal iron. Irradiation by sunlight only affected the Fe/H(2)O(2) system, leading to a 5.5-fold increase in k(obs) (up to 3.1 min(-1)). HO(*) production, measured by electron spin resonance, could not account for the observed inactivation in the Fe/H(2)O(2) system. Other oxidants, such as ferryl species, must therefore play a role. Experiments using bulk oxidant scavengers revealed that inactivation occurred by a caged mechanism involving oxidant production by metals located in close proximity to the virus. Overall, our results show that the Fenton/photo-Fenton process may serve as an efficient technology for virus disinfection. PMID- 20356039 TI - What the cell "sees" in bionanoscience. AB - What the biological cell, organ, or barrier actually "sees" when interacting with a nanoparticle dispersed in a biological medium likely matters more than the bare material properties of the particle itself. Typically the bare surface of the particle is covered by several biomolecules, including a select group of proteins drawn from the biological medium. Here, we apply several different methodologies, in a time-resolved manner, to follow the lifetime of such biomolecular "coronas" both in situ and isolated from the excess plasma. We find that such particle biomolecule complexes can be physically isolated from the surrounding medium and studied in some detail, without altering their structure. For several nanomaterial types, we find that blood plasma-derived coronas are sufficiently long-lived that they, rather than the nanomaterial surface, are likely to be what the cell sees. From fundamental science to regulatory safety, current efforts to classify the biological impacts of nanomaterials (currently according to bare material type and bare surface properties) may be assisted by the methodology and understanding reported here. PMID- 20356038 TI - How active-site protonation state influences the reactivity and ligation of the heme in chlorite dismutase. AB - Chlorite dismutase catalyzes O(2) release from chlorite with exquisite efficiency and specificity. The spectroscopic properties, ligand binding affinities, and steady-state kinetics of chlorite dismutase from Dechloromonas aromatica were examined over pH 3-11.5 to gain insight into how the protonation state of the heme environment influences dioxygen formation. An acid-base transition was observed by UV/visible and resonance Raman (rR) spectroscopy with a pK(a) of 8.7, 2-3 pH units below analogous transitions observed in typical His-ligated peroxidases. This transition marks the conversion of a five-coordinate high-spin Fe(III) to a mixed high/low-spin ferric hydroxide, as confirmed by rR spectroscopy. The two Fe-OH stretching frequencies are quite low, consistent with a weak Fe-OH bond, despite the nearly neutral imidazole side chain of the proximal histidine ligand. The hydroxide is proposed to interact strongly with a distal H-bond donor, thereby weakening the Fe-OH bond. The rR spectra of Cld-CO as a function of pH reveal two forms of the complex, one in which there is minimal interaction of distal residues with the carbonyl oxygen and another, acidic form in which the oxygen is under the influence of positive charge. Recent crystallographic data reveal arginine 183 as the lone H-bond-donating residue in the distal pocket. It is likely that this Arg is the strong, positively charged H bond donor implicated by vibrational data to interact with exogenous axial heme ligands. The same Arg in its neutral (pK(a) approximately 6.5) form also appears to act as the active-site base in binding reactions of protonated ligands, such as HCN, to ferric Cld. The steady-state profile for the rate of chlorite decomposition is characterized by these same pK(a) values. The five-coordinate high-spin acidic Cld is more active than the alkaline hydroxide-bound form. The acid form decomposes chlorite most efficiently when the distal Arg is protonated/cationic (maximum k(cat) = 2.0(+/-0.6) x 10(5) s(-1), k(cat)/K(M) = 3.2(+/-0.4) x 10(7) M(-1) s(-1), pH 5.2, 4 degrees C) and to a somewhat lesser extent when it acts as a H-bond donor to the axial hydroxide ligand under alkaline conditions. PMID- 20356040 TI - Revealing the lytic mechanism of the antimicrobial peptide gomesin by observing giant unilamellar vesicles. AB - Gomesin (Gm) is a potent cationic antimicrobial peptide from a Brazilian spider. Here we use optical and fluorescence microscopy to study the interaction of Gm, its low active linear analogue, [Ser(2,6,11,15)]-Gm (GmL), and a fluorescent labeled analogue, Gm-Rh, with giant unilamellar vesicles (GUVs) composed of mixtures of the neutral lipid palmitoyloleoyl phosphatidylcholine (POPC) with the negatively charged lipid palmitoyloleoyl phosphatidylglycerol (POPG) or cholesterol, so as to mimic bacterial and mammalian cell membranes, respectively. We observed the effect of injecting a peptide solution with a micropipet close to GUVs. As a result of peptide-lipid interaction, GUVs burst suddenly. Stable pores, which result in leaky vesicles, were not observed. Fluorescence microscopy of Gm-Rh injected on GUVs confirmed the high peptide/lipid affinity. These facts lead us to suggest that Gm and GmL disrupt the membrane via the carpet model. In order to quantify the lytic activity of both peptides against different membrane composition, a solution of GUVs was diluted in increasing concentration of peptides and the fraction of burst GUVs was measured as a function of time. The lytic activity of both peptides was enhanced by the presence of POPG and decreased upon addition of cholesterol. GmL exhibited lower lytic activity as compared to Gm, but this difference vanished at high POPG molar fraction. PMID- 20356041 TI - Isoliquiritigenin suppresses the Toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent signaling pathway of Toll-like receptors by targeting TBK1. AB - Toll-like receptors (TLRs) play an important role in induction of innate immune responses. TLRs can trigger the activation of myeloid differential factor 88 (MyD88)- and Toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling pathways. Expression of more than 70% of lipopolysaccharide (LPS)-induced target genes is mediated through a TRIF-dependent signaling pathway. To evaluate the therapeutic potential of isoliquiritigenin (ILG), we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs. ILG inhibited interferon regulatory factor 3 activation induced by LPS or polyinosinic-polycytidylic acid, as well as interferon-inducible genes, such as interferon-inducible protein-10. ILG attenuated ligand-independent activation of IRF3 induced by TRIF or TBK1. Furthermore, ILG inhibited TBK1 kinase activity in vitro. Together, these results demonstrate that TBK1 is the molecular target of ILG, resulting in the downregulation of the TRIF-dependent signaling pathways of TLRs. PMID- 20356042 TI - An onion byproduct affects plasma lipids in healthy rats. AB - Onion may contribute to the health effects associated with high fruit and vegetable consumption. A considerable amount of onion production ends up as waste that might find use in foods. Onion byproduct has not yet been explored for potential health benefits. The aim of this study is to elucidate the safety and potential role of onion byproducts in affecting risk markers of cardiovascular disease (CVD). For that purpose, the effects of an onion byproduct, Allium cepa L. cepa 'Recas' (OBP), and its two derived fractions, an ethanolic extract (OE) and a residue (OR), on the distribution of plasma lipids and on factors affecting cholesterol metabolism in healthy rats have been investigated. The OBP or its fractions did not significantly reduce cholesterol or down-regulate hepatic 3 hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) gene expression. The OR even had the effect of increasing plasma triacylglycerides (TAG) and cholesterol in the very low density lipoprotein (VLDL-C) fraction. Neither total bile acids nor total primary or secondary bile acids were significantly affected by feeding rats the OBP or its fractions. Principal component analysis combining all markers revealed that the controls could be completely separated from OBP, OE, and OR groups in the scores plot and also that OE and OR groups were separated. Plasma lipids and bile acid excretion were the discriminating loading factors for separating OE and OR but also contributed to the separation of onion-fed animals and controls. It was concluded that the onion byproduct did not present significant beneficial effects on individual markers related to plasma lipid transport in this healthy rat model but that onion byproduct contains factors with the ability to modulate plasma lipids and lipoprotein levels. PMID- 20356043 TI - Conformational preferences of a 14-residue fibrillogenic peptide from acetylcholinesterase. AB - A 14-residue fragment from near the C-terminus of the enzyme acetylcholinesterase (AChE) is believed to have a neurotoxic/neurotrophic effect acting via an unknown pathway. While the peptide is alpha-helical in the full-length enzyme, the structure and association mechanism of the fragment are unknown. Using multiple molecular dynamics simulations, starting from a tetrameric complex of the association domain of AChE and systematically disassembled subsets that include the peptide fragment, we show that the fragment is incapable of retaining its helicity in solution. Extensive replica exchange Monte Carlo folding and unfolding simulations in implicit solvent with capped and uncapped termini failed to converge to any consistent cluster of structures, suggesting that the fragment remains largely unstructured in solution under the conditions considered. Furthermore, extended molecular dynamics simulations of two steric zipper models show that the peptide is likely to form a zipper with antiparallel sheets and that peptides with mutations known to prevent fibril formation likely do so by interfering with this packing. The results demonstrate how the local environment of a peptide can stabilize a particular conformation. PMID- 20356044 TI - Study of the physical properties of whey protein isolate and gelatin composite films. AB - The relationships between the microstructural and physical properties of the whey protein isolate and gelatin (WPI/gelatin) composite films were investigated in the present work. Through the electrostatic effects at pH 8, WPI and gelatin molecules could form compact aggregates in solution, where a remarkable shrinkage of the gelatin molecules was observed, when the WPI/gelatin mass ratio was close to 50W:50G. FT-IR analysis indicated that hydrogen bonding also involved the aggregation and film-forming process. The melting temperature of the 50W:50G composite film increased by 9 degrees C compared with the single component films. However, this aggregation process also made the film network microstructure discontinuous, and led to a decline of the puncture strength of the film near 50W:50G; in contrast, the deformation and water vapor permeability of the composite films increased with the gelatin content, while the moisture content and solubility did not show significant variations. PMID- 20356045 TI - 6-dehydrogingerdione sensitizes human hepatoblastoma Hep G2 cells to TRAIL induced apoptosis via reactive oxygen species-mediated increase of DR5. AB - The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale , and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial- and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial- and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells. PMID- 20356046 TI - Protein patterning by UV-induced photodegradation of poly(oligo(ethylene glycol) methacrylate) brushes. AB - The UV photodegradation of protein-resistant poly(oligo(ethylene glycol) methacrylate) (POEGMA) bottle-brush films, grown on silicon oxide by surface initiated atom radical transfer polymerization, was studied using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Exposure to light with a wavelength of 244 nm caused a loss of polyether units from the brush structure and the creation of aldehyde groups that could be derivatized with amines. An increase was measured in the coefficient of friction of the photodegraded polymer brush compared to the native brush, attributed to the creation of a heterogeneous surface film, leading to increased energy dissipation through film deformation and the creation of new polar functional groups at the surface. Exposure of the films through a photomask yielded sharp, well-defined patterns. Analysis of topographical images showed that physical removal of material occurred during exposure, at a rate of 1.35 nm J(-1) cm(2). Using fluorescence microscopy, the adsorption of labeled proteins onto the exposed surfaces was studied. It was found that protein strongly adsorbed to exposed areas, while the masked regions retained their protein resistance. Exposure of the film to UV light from a scanning near-field optical microscope yielded submicrometer-scale patterns. These data indicate that a simple, rapid, one-step photoconversion of the poly(OEGMA) brush occurs that transforms it from a highly protein-resistant material to one that adsorbs protein and can covalently bind amine-containing molecules and that this photoconversion can be spatially addressed with high spatial resolution. PMID- 20356047 TI - Investigation of multiphase liquid roughness using an atomic force microscope. AB - The roughness of a multiphase interface and the associated topography between silicone oil and an alcohol-based fluid were measured with an atomic force microscope (AFM) and compared with the results of calculations based upon a capillary-wave model. According to this theory, the interfacial roughness of a liquid-liquid interface depends on the density, interfacial tension, and temperature of the liquids. Test samples prepared with both silicone oil and an alcohol-based fluid at various volumetric ratios and controlled temperatures were carefully measured. The experimental results indicate that the interfacial roughness measured with an AFM was consistent with the capillary-wave model. The measured interfacial roughness is influenced mainly by the interfacial tension between the liquids and the temperature-driven Brownian motion of the molecules. Three-dimensional topographical pictures of the interfaces were constructed and archived digitally for subsequent investigation. By employing the outlined method, we examined the microscopic details of interfacial properties, with prospective applications in biochemical and biophysical research. PMID- 20356048 TI - A new approach for the characterization of reverse micellar systems by dynamic light scattering. AB - This paper reports the use of dynamic light scattering (DLS) to study reverse micelles formed by the water/Igepal CO-520/cyclohexane system over a large range of global compositions. A novel approach for data analysis is presented, based on the realization that micelles of a given size must be in equilibrium with free surfactant of a fixed concentration. Compilation of the DLS data into sets of fixed micelle size but differing global compositions therefore allows for the determination of parameters such as free surfactant concentration, micellar molar composition, surfactant interfacial area, and aggregation numbers. Importantly, this method gives access to the variation of each of these parameters with micelle size, as is essential for the characterization of reverse micelles formed by nonionic surfactants. This approach constitutes a significant complement to other available characterization methods. The analysis also provides insight into the primary factors controlling the equilibrium distribution of surfactant within the system and the relative stability of the micelles. PMID- 20356049 TI - Ultrathin n-type organic nanoribbons with high photoconductivity and application in optoelectronic vapor sensing of explosives. AB - Well-defined ultrathin nanoribbons have been fabricated from an amphiphilic electron donor-acceptor (D-A) supramolecule comprising perylene tetracarboxylic diimide as the backbone scaffold to enforce the one-dimensional intermolecular assembly via strong pi-stacking. These nanoribbons demonstrated high photoconductivity upon illumination with white light. The high photoconductivity thus obtained is likely due to the optimal molecular design that enables a good kinetic balance between the two competitive processes, the intramolecular charge recombination (between D and A) and the intermolecular charge transport along the nanoribbon. The photoconduction response has also proven to be prompt and reproducible with the light turning on and off. The photogenerated electrons within the nanoribbon can be efficiently trapped by the adsorbed oxygen molecules or other oxidizing species, leading to depletion of the charge carriers (and thus the electrical conductivity) of the nanoribbon, as typically observed for n-type semiconductor materials as applied in chemiresistors. Combination of this sensitive modulation of conductivity with the unique features intrinsic to the nanoribbon morphology (large surface area and continuous nanoporosity when deposited on a substrate to form a fibril film) enables efficient vapor sensing of nitro-based explosives. PMID- 20356050 TI - Spending your energy. PMID- 20356051 TI - Rapid screening of fatty acids using nanostructure-initiator mass spectrometry. AB - We present the application of nanostructure-initiator mass spectrometry (NIMS) as a fast and simple method for the analysis of plant and microbial fatty acids. NIMS allowed the direct detection of a broad range of saturated and unsaturated fatty acids in negative mode showing linearity over several orders of magnitude with a limit of detection at the femtomole level. Additionally, the fatty acid compositions of olive and soybean oil and the algal species Chlamydomonas reinhardtii could be determined both qualitatively and quantitatively with only minimal sample volumes and preparation steps. The unique properties of the NIMS surface allowed for an in situ sample cleanup step leading to a more than 10-fold increase of the signal-to-noise ratio. Our data provide the basis for rapid screening of plant and microbial oils and may aid in the development of biodiesel fuels. PMID- 20356052 TI - Mapping of fluidic mixing in microdroplets with 1 micros time resolution using fluorescence lifetime imaging. AB - Microdroplets generated in microfluidic channels hold great promise for use as substrates in high-throughput chemical and biological analysis. These water-in oil compartments can serve as isolated reaction vessels, and since they can be generated at rates in excess of 1 kHz, thousands of assays can be carried out quickly and reproducibly. Nevertheless, sampling the large amount of information generated from these platforms still remains a significant challenge. For example, considering the high droplet generation rates and velocities, reproducibility and micrometer resolution are challenging requirements that must be fulfilled. Herein we combine confocal fluorescence lifetime imaging microscopy with a statistical implementation that permits the analysis of mixing phenomena within microdroplets with a temporal resolution of 1 mus. Importantly, such exquisite resolution is only possible as a result of the large number of droplets sampled and their high structural reproducibility. PMID- 20356053 TI - Maskless and resist-free rapid prototyping of three-dimensional structures through electron beam induced deposition (EBID) of carbon in combination with metal-assisted chemical etching (MaCE) of silicon. AB - In this work, we introduce a maskless, resist-free rapid prototyping method to fabricate three-dimensional structures using electron beam induced deposition (EBID) of amorphous carbon (aC) from a residual hydrocarbon precursor in combination with metal-assisted chemical etching (MaCE) of silicon. We demonstrate that EBID-made patterned aC coating, with thickness of even a few nanometers, acts as a negative "mask" for the etching process and is sufficient for localized termination of the MaCE of silicon. Optimal aC deposition settings and gold film thickness for fabrication of high-aspect-ratio nanoscale 3D silicon structures are determined. The speed necessary for optimal aC feature deposition is found to be comparable to the writing speed of standard Electron Beam Lithography and the MaCE etching rate is found to be comparable to standard deep reactive ion etching (DRIE) rate. PMID- 20356054 TI - Radical directed dissociation for facile identification of iodotyrosine residues using electrospray ionization mass spectrometry. AB - Iodination of tyrosine residues in proteins has many uses in chemistry, biology, and medicine. Site specific identification of the sites of iodination is important for many of these uses. Reported herein is a facile method employing photodissociation and mass spectrometry to localize sites of iodination in whole proteins. Absorption of ultraviolet photons by iodotyrosine results in loss of iodine via homolytic bond dissociation. The resulting protein radical fragments in the vicinity of the iodotyrosine upon collisional activation. Analysis of the fragments within the vicinity of each tyrosine residue in the protein enables quantitative evaluation of the likelihood for iodination at each site. The results are compared with both traditional bottom up and top down mass spectrometric methods. Radical directed dissociation yields results in agreement with traditional approaches but requires significantly less effort and is inherently more sensitive. One limitation occurs when multiple tyrosine residues are in close proximity, in which case the extent of iodination at each residue may be difficult to determine. This limitation is frequently problematic for traditional approaches as well. PMID- 20356055 TI - Gap structure effects on surface-enhanced Raman scattering intensities for gold gapped rods. AB - Gapped rods provide a unique platform for elucidating structure/function relationships, both for single-molecule electrochemical techniques and for surface-enhanced Raman scattering (SERS). This paper attempts to elucidate the dependence of SERS intensities on gap topography and gap distance for gold gapped rods with segment lengths varying over a wide range (40-2000 nm). Significantly, we have determined that rough gaps lead to a smaller SERS enhancement than smooth gaps for these structures even though the rough gaps have a larger total surface area. Both theory and experiment show periodic variation of SERS intensity with segment length as determined by odd-symmetry plasmon multipoles. Excitation of even-symmetry modes is dipole forbidden (for polarization along the rod axis), but this selection rule can be relaxed by roughness or, for smooth gaps, by near field coupling between the rod segments. PMID- 20356056 TI - Hydroxynaphthoquinone ultrathin films obtained by diazonium electroreduction: toward design of biosensitive electroactive interfaces. AB - Electroactive 2-(phenylsulfanyl)-8-hydroxy-1,4-naphthoquinone has been electrodeposited via the reduction of the corresponding diazonium salt on Au electrodes. Surface characterizations by X-ray photoelectron spectroscopy (XPS) and infrared reflection-absorption spectroscopy (IRRAS) reveal that the mechanism of film deposition follows an aryl radical formation and its immobilization on the electrode surface. Electrochemical study shows that the surface coverage can be finely tuned (thickness between one and four layers) by adjusting the potential and the deposition time. By managing the potential applied when reducing diazonium in potentiostatic mode, the formed layer could mediate or not charge transfer. This is the first time that the films obtained by diazonium process are demonstrated to act as mediators in the growth process. Hence, with potentials higher than the formal potential of quinone group, very thin and homogeneous layers are obtained, whereas thicker films are formed when more cathodic potentials than that of quinone are applied. The possibility to manage the charge-transfer kinetics, the thickness, and the homogeneity of electroactive deposits is interesting in the scope of designing electrochemical transducers. PMID- 20356057 TI - Propagating surface plasmon resonance on microhole arrays. AB - Metallic thin films patterned with micrometer size triangle or hole arrays present plasmonic properties when excited in the Kretschmann configuration, that are improved in comparison to conventional thin film surface plasmon resonance (SPR). These optical properties can be tuned by varying the physical aspects of the microplasmonic structures. Triangles and microhole arrays were prepared with modified nanosphere lithography (NSL) using latex spheres of 0.65, 0.82, 1.0, 1.5, or 3.2 microm in diameter. This allowed the preparation of triangles with edge lengths between 275 to 2000 nm and microhole arrays of various periodicities, diameters, and hole depths. These microstructures were studied to understand the relationship between the physical aspects and the optical properties, such as the sensitivity, working refractive index range, spectral width of the plasmonic peaks, spectral noise, and refractive index resolution. Microhole arrays with a hole diameter equal to half the periodicity were found to combine the advantages of both localized surface plasmon resonance (LSPR) on nanoparticles and SPR on a thin film. These microhole arrays exhibited high sensitivity to refractive index (>3000 nm/RIU), sensitivity to monolayer formation (2-fold improvement compared to thin films), and excellent refractive index resolution (10(-6) RIU). Finally, a biosensor for the detection of 10 nM of immunoglobulin G (IgG) exhibited a greater response with microplasmonic materials compared to conventional thin Au films. Hence, these novel plasmonic materials exhibit a strong potential as an SPR sensing platform. They can be implemented on existing instrumentation and use detection protocols developed for current SPR sensors. PMID- 20356058 TI - Molecular, electronic, and crystal structures of self-assembled hydrothermally synthesized Zn(II)-mercaptonicotinate: a combined spectroscopic and theoretical approach. AB - A Zn(II) 2-mercaptonicotinate coordination polymer (Zn1), with Zn(II) ions chelated by both sulfur and oxygen in a distorted square pyramidal environment, and a molecular Zn(II) 2-hydroxynicotinate complex (Zn2) were synthesized by the reaction of zinc acetylacetonate with 2-mercaptonicotinic (Zn1) and 2 hydroxynicotinc (Zn2) acid, respectively, under hydrothermal conditions. The crystal structures of Zn1 and Zn2 were determined by single crystal X-ray diffraction measurements. Dispersion-corrected density functional theory (DFT) calculations reproduce very well the experimental structures and show that Zn1 is stable against hydration, whereas Zn2 is stable against dehydration over wide ranges of temperature and pressure, in agreement with thermogravimetric analysis results. The electronic structure of the two compounds is computed with the DFT+U method. The theoretical valence band agrees well with the X-ray photoelectron spectroscopy experiments. Furthermore, the band gap of Zn1 is found to be narrower than that of Zn1 and is characterized by the presence of sulfur lone pairs at the edge of the valence band. PMID- 20356059 TI - Ultrafast all-optical switching in a silicon-nanocrystal-based silicon slot waveguide at telecom wavelengths. AB - We demonstrate experimentally all-optical switching on a silicon chip at telecom wavelengths. The switching device comprises a compact ring resonator formed by horizontal silicon slot waveguides filled with highly nonlinear silicon nanocrystals in silica. When pumping at power levels about 100 mW using 10 ps pulses, more than 50% modulation depth is observed at the switch output. The switch performs about 1 order of magnitude faster than previous approaches on silicon and is fully fabricated using complementary metal oxide semiconductor technologies. PMID- 20356060 TI - Microfluidic mixing and the formation of nanoscale lipid vesicles. AB - We investigate the formation of unilamellar lipid vesicles (liposomes) with diameters of tens of nanometers by controlled microfluidic mixing and nanoparticle determination (COMMAND). Our study includes liposome synthesis experiments and numerical modeling of our microfluidic implementation of the batch solvent injection method. We consider microfluidic liposome formation from the perspective of fluid interfaces and convective-diffusive mixing, as we find that bulk fluid flow parameters including hydrodynamically focused alcohol stream width, final alcohol concentration, and shear stress do not primarily determine the vesicle formation process. Microfluidic device geometry in conjunction with hydrodynamic flow focusing strongly influences vesicle size distributions, providing a coarse method to control liposome size, while total flow rate allows fine-tuning the vesicle size in certain focusing regimes. Although microfluidic liposome synthesis is relatively simple to implement experimentally, numerical simulations of the mixing process reveal a complex system of fluid flow and mass transfer determining the formation of nonequilibrium vesicles. These results expand our understanding of the microfluidic environment that controls liposome self-assembly and yield several technological advances for the on-chip synthesis of nanoscale lipid vesicles. PMID- 20356061 TI - Asymmetric total synthesis of the caspase-1 inhibitor (-)-berkeleyamide A. AB - The asymmetric total synthesis of (-)-berkeleyamide A (1), a naturally occurring caspase-1 inhibitor, has been achieved by employing Evans' syn-aldol reaction of N-acyl-(4R)-benzyl oxazolidin-2-one 3 as the key step. PMID- 20356062 TI - Dynamical formation of spatially localized arrays of aligned nanowires in plastic films with magnetic anisotropy. AB - We present a simple technique for magnetic-field-induced formation, assembling, and positioning of magnetic nanowires in a polymer film. Starting from a polymer/iron oxide nanoparticle casted solution that is allowed to dry along with the application of a weak magnetic field, nanocomposite films incorporating aligned nanocrystal-built nanowire arrays are obtained. The control of the dimensions of the nanowires and of their localization across the polymer matrix is achieved by varying the duration of the applied magnetic field, in combination with the evaporation dynamics. These multifunctional anisotropic free-standing nanocomposite films, which demonstrate high magnetic anisotropy, can be used in a wide field of technological applications, ranging from sensors to microfluidics and magnetic devices. PMID- 20356063 TI - Semisynthesis of natural flavones inhibiting tubulin polymerization, from hesperidin. AB - Semisynthesis of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (1), a natural flavone that binds with high affinity to tubulin, was performed from hesperidin, the very abundant Citrus flavanone, by a five-step sequence. The last step of the synthesis also gave rise to 5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone (= casticin or vitexicarpin) (10), 5,3'-dihydroxy-3,7,8,4'-tetramethoxyflavone (= gossypetin 3,7,8,4'-tetramethyl ether) (11), and, unexpectedly, 5,7,3'-trihydroxy 3,6,8,4'-tetramethoxyflavone (12) and 5,3'-dihydroxy-8-dimethylamino-3,6,7,4' tetramethoxyflavone (= 8-dimethylaminocasticin) (13). Cytotoxicity and antitubulin activity of these five flavones, as well as 5,3'-dihydroxy-3,7,4' trimethoxyflavone (= ayanin) (14) and intermediate 6,8-dibromo-ayanin (8), were evaluated. Comparison of the responses confirmed and clarified the influence of the A-ring substitution pattern on the biological activity. PMID- 20356064 TI - cis-Clerodane-type furanoditerpenoids from Tinospora crispa. AB - Phytochemical and cytotoxicity investigations on organic solvent extracts of the aerial parts of Tinospora crispa have led to the isolation of 15 cis-clerodane type furanoditerpenoids. Of these, nine compounds (1-9) were found to be new. Spectroscopic assignments of a previously reported compound, borapetoside A (13), were revised on the basis of HMQC and HMBC correlations. No discernible activity was observed when compounds 10-13 were subjected to evaluation in cytotoxicity assays against human prostate cancer (PC-3) and the normal mouse fibroblast (3T3) cell lines. PMID- 20356065 TI - Total synthesis of (-)-aurantioclavine. AB - The concise total synthesis of (-)-aurantioclavine has been achieved by taking advantage of strategies for the asymmetric alkenylation of N-tert-butanesulfinyl imines. The enantiomerically pure natural product was prepared in 6 steps and 27% overall yield by using Rh-catalyzed addition of a N-methyliminodiacetic acid (MIDA) boronate and in 5 steps and 29% yield by employing a Grignard reagent addition sequence. PMID- 20356066 TI - Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups. AB - In this paper, a novel synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups is presented. Anionically activated trifluoromethyl groups react with secondary amines under aqueous conditions to afford tertiary amides. The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%). PMID- 20356067 TI - First Zn(II) bowl-complexes modeling the tris(histidine) metallo-site of enzymes. AB - The bowl-shaped resorcin[4]arene-based ligand was prepared as a model of the trihistidine coordination core present in many mononuclear metalloenzymes. The CH(2)-O-CH(2)- linkers connecting the imidazoles to the cavity allow three imidazoles to simultaneously bind a metal ion, and favor cis-coordination of two exchangeable ligands. The corresponding mononuclear Zn(II) complexes were shown to be capable of the selective guest binding and exchange at both endo and exo positions. PMID- 20356068 TI - [8-[Bis(carboxymethyl)aminomethyl]-6-bromo-7-hydroxycoumarin-4-yl]methyl moieties as photoremovable protecting groups for compounds with COOH, NH2, OH, and C=O functions. AB - We introduce a variant of coumarin-based photoactivatable protecting groups and use it exemplarily for caging of a carboxylic acid, an amine, a phenol, and a carbonyl compound. The caged compounds are efficiently photolyzed at long wavelength UV/vis irradiation. Compared to the corresponding (6-bromo-7 hydroxycoumarin-4-yl)methyl (Bhc) derivatives, the novel coumarin-type caged compounds are distinguished by (i) dramatically increased solubilities in aqueous buffers, (ii) lower pK(a) values of the C7 hydroxyl of the coumarin chromophore, thus permitting efficient photorelease at lower pH, and (iii) higher photolysis quantum yields in the case of photoprotected carbonyl compounds. The primary step of the photocleavages occurs with rate constants of about 10(9) s(-1). PMID- 20356069 TI - Palladium-catalyzed dehydrogenative direct arylations of 1,2,3-triazoles. AB - Palladium-catalyzed intramolecular dehydrogenative direct arylations of 1,2,3 triazoles were accomplished under ambient pressure of air, which set the stage for a modular synthesis of annulated phenanthrenes through a reaction sequence comprising two distinct catalytic C-H bond functionalization reactions. PMID- 20356070 TI - The tert-butylsulfinamide lynchpin in transition-metal-mediated multiscaffold library synthesis. AB - A unified synthetic approach to diverse polycyclic scaffolds has been developed using transition-metal-mediated cycloaddition and cyclization reactions of enynes and diynes. The tert-butylsulfinamide group has been identified as a particularly versatile lynchpin in these reactions, with a reactivity profile uniquely suited for efficient, stereoselective substrate synthesis and downstream transformations. This approach provides 10 distinct, functionalized scaffold classes related to common core structures in alkaloid and terpenoid natural products. PMID- 20356071 TI - Chemoselective protection of alpha-ketoacids by direct annulations with oximes. AB - Oximes and alpha-ketoacids undergo an unexpectedly facile and chemoselective annulation to afford 2,5-dihydrooxazole 3-oxides. The resulting cyclic nitrones serve as chemically and configurationally stable masked alpha-ketoacids that can be easily elaborated and manipulated. Deprotection is achieved by mild reduction with zinc metal and hydrolysis. This methodology allows for the protection, elaboration, and deprotection of enantiopure peptide derived alpha-ketoacids, which are the key starting materials for the chemoselective ketoacid hydroxylamine peptide ligation. PMID- 20356072 TI - Phospholipidosis as a function of basicity, lipophilicity, and volume of distribution of compounds. AB - Drug-induced phospholipidosis (PLD) is an adaptive histologic alteration that is seen with various marketed drugs and often encountered during drug development. Various in silico and in vitro cell-based methods have been developed to predict the PLD-inducing potential of compounds. These methods rely on the inherent physicochemical properties of the molecule and, as such, tend to overpredict compounds as PLD inducers. Recognizing that the distribution of compounds into tissues or tissue accumulation is likely a key factor in PLD induction, in addition to key physicochemical properties, we developed a model to predict PLD in vivo using the measures of basicity (pK(a)), lipophilicity (ClogP), and volume of distribution (V(d)). Using sets of PLD inducers and noninducers, we demonstrate improved concordance with this method. Furthermore, we propose a screening paradigm that includes a combination of various methods to predict the in vivo PLD-inducing potential of compounds, which may be especially useful in lead identification and optimization processes in drug discovery. PMID- 20356073 TI - Half-metallic ferromagnetism and large negative magnetoresistance in the new lacunar spinel GaTi3VS8. AB - The lacunar spinel compounds GaTi(4-x)V(x)S(8) (0 < x < 4), consisting of Ti(4 x)V(x) tetrahedral clusters, were prepared and their structures were determined by powder X-ray diffraction. The electronic structures of GaTi(4-x)V(x)S(8) (x = 0, 1, 2, 3) were examined by density functional calculations, and the electrical resistivity and magnetic susceptibility of these compounds were measured. Our calculations predict that GaTi(3)VS(8) is a ferromagnetic half-metal, and this prediction was confirmed by magnetotransport experiments performed on polycrystalline samples of GaTi(3)VS(8). The latter reveal a large negative magnetoresistance (up to 22% at 2 K), which is consistent with the intergrain tunnelling magnetoresistance expected for powder samples of a ferromagnetic half metal and indicates the presence of high spin polarization greater than 53% in GaTi(3)VS(8). PMID- 20356075 TI - Oxidation of titanium-decorated single-walled carbon nanotubes and subsequent reduction by lithium. AB - The chemical surface structure of Ti-decorated single-walled carbon nanotubes (SWNTs) is studied. X-ray photoelectron spectra show that Ti adatoms on the SWNT surface oxidize even under ultra-high-vacuum conditions, presenting a serious obstacle for the use of Ti-decorated SWNTs for hydrogen storage. A subsequent deposition of Li can, however, reduce the degree of Ti oxidation, "liberating" Ti atoms for the interaction with hydrogen molecules in hydrogen storage applications. PMID- 20356076 TI - Effect of preprocessing olive storage conditions on virgin olive oil quality and composition. AB - The quality of virgin olive oil (VOO) is intimately related to the characteristics and composition of the olive fruit at the moment of its milling. In this study, the determination of suitable olive storage conditions and feasibility of using this preprocessing operation to modulate the sensory taste of VOO are reported. Several olive batches were stored in different conditions (from monolayer up to 60 cm thickness, at 20 and 10 degrees C) for a period of up to three weeks, and the quality and composition of minor constituents, mainly phenols and volatiles, in the corresponding VOO were monitored. Cornicabra cultivar VOO obtained from drupes stored for 5 or 8 days at 20 or 10 degrees C, respectively, retained the "extra virgin" category, according to chemical quality indices, since only small increases in free acidity and peroxide values were observed, and the bitter index of this monovarietal oil was reduced by 30-40%. Storage under monolayer conditions at 10 degrees C for up to two weeks is also feasible because "off-odor" development was delayed, a 50% reduction in bitterness was obtained, and the overall good quality of the final product was preserved. PMID- 20356077 TI - Endotoxin levels at Swine farms using different waste treatment and management technologies. AB - Concentrated animal feeding operations (CAFOs) are a major source of airborne endotoxins, which are air pollutants that can cause adverse health effects to both on-site farmers and neighbors. Release of airborne endotoxins to the environment can be reduced using proper waste treatment and management technologies. In this study, the levels of endotoxins released from two swine CAFOs using conventional lagoon-sprayfield technology were compared to those of 15 farms using various alternative waste management technologies in North Carolina. Over a 2-year period, 236 endotoxin samples were collected from the 17 farm units and analyzed using the Limulus amebocyte lysate (LAL) test. Concentrations of airborne endotoxins near barn exhaust fans were significantly higher than at the upwind boundary of the farm and at other farm sites. For most of the study sites, mean concentrations of endotoxins at the downwind boundary of the farm were higher than those at the upwind boundary of the farm, indicating the release of endotoxins from swine CAFOs to the neighboring environment. Endotoxin levels were significantly associated with concentrations of airborne bacteria but not fungi. Environmental factors, such as temperature, relative humidity, and wind velocity, affected the levels of airborne endotoxins at the farms. Based on the ratios of airborne endotoxins in downwind and upwind samples from the farm units, at least five different alternative waste management technologies significantly reduced the release of endotoxins from swine CAFOs. These results suggest that swine CAFOs are important sources of airborne endotoxins, the levels of which can be reduced by applying more robust and effective waste management technologies. PMID- 20356079 TI - Evidence for self-association of nonionic and other organic solutes in liquid phases comprising 1-octanol and water. AB - We use a monomer-single-multimer model to judge whether there is significant self association of an organic solute distributed between 1-octanol and water. Self association leads to octanol-water partition coefficients, K(ow), that depend upon the concentration of solute and this affects their application, significantly so for lipophilic compounds. Our measurements, done over as wide a range of concentration as possible, suggest that: (1) For toluene, there is dimerization in the water and tetramerization in 1-octanol. (2) For p-xylene, there is significant self-association of unknown degree in 1-octanol. (3) Biphenyl exhibits no self-association in either phase. The model confirms the conclusion that there is self-association of nicotimamide only in the aqueous phase, a conclusion reached in original measurements and interpretation (Charman, W. N.; Lai, C. S. C.; Finnin, B. C.; Reed, B. L. Pharm. Res. 1991, 8, 1144-1150). Our analysis of published measurements on the four isomers of hexachlorocyclohexanes (Paschke, A.; Shuurmann, G. Chem. Eng. Technol. 2000, 23, 666-670) leads to the conclusion that there is significant self-association of unknown degree in the aqueous phase. There is a discernible region of concentration-independent behavior as infinite dilution is approached in the aqueous phase, except notably for the hexachlorocyclohexanes. We suggest this is due to self-association incorporating the solvent to form multimer-solvent complexes. The data suggest that self-association, when it occurs, has a greater significance in the more lipophilic cases and this may partly explain why the variability in measurements of octanol-water partition coefficients between laboratories tends to be larger and significant for more lipophilic solutes. PMID- 20356080 TI - Sensory, chemical, and electronic tongue assessment of micro-oxygenated wines and oak chip maceration: assessing the commonality of analytical techniques. AB - Micro-oxygenation (MOX) was conducted in the presence and absence of oak chips at rates to mimic oxygen ingress during barrel maturation of red wine. Following MOX, wines were analyzed for chemical attributes pertaining to phenolic composition and assessed by a trained sensory panel. An electronic tongue (ET) was also used to assess the wines. Variations in chemical attributes were found to be mostly influenced by vintage, followed by oak chip maceration accounting for 48% and 16% of variation within the data set, respectively. MOX treatment accounted for 11% of variability within the physiochemical data set, with attributes pertaining to anthocyanin polymerization and levels of sulfur dioxide in the finished wine being most significantly influenced. A generalized Procrustes rotation and alignment of the chemical, electronic tongue, and sensory data sets followed by PLS1 regressions showed good prediction of the sensory characters oak, pencil shavings, stewed plum, vegetal, and spice over the range of sensory scores from the ET data; bitterness and astringency could also be predicted from the physicochemical data with good precision. PMID- 20356081 TI - Effect of micronutrient-enriched sunflower oils on plasma lipid profile and antioxidant status in high-fat-fed rats. AB - The main objective of this study was to evaluate in vivo whether micronutrient enriched high-oleic sunflower oils (optimized oils) obtained using different crushing and refining procedures could have any beneficial effect on plasma lipid profile and antioxidant status. Sprague-Dawley rats were fed a high-fat diet for 4 weeks. The lipid source consisted of 20% optimized sunflower oils with different quantities and qualities of micronutrients. The control group received traditional refined high-oleic sunflower oil. The experimental optimized oils in the diets had a hypolipidemic effect. The reduction in plasma triglyceride and total cholesterol levels was 43% and 20%, respectively, in the group fed the diet with the highest levels of micronutrients. The serum ferric antioxidant capacity, superoxide dismutase, glutathione peroxidase and reduced glutathione significantly increased and lipid peroxidation decreased in parallel with the enhancement of micronutrients. These results suggest that a regular intake of optimized sunflower oils can help to improve lipid status and reduce lipid peroxidation in plasma. PMID- 20356082 TI - Electronic substituent effects in bicyclo[1.1.1]pentane and [n]staffane derivatives: a quantum chemical study based on structural variation. AB - The transmission of electronic substituent effects through one or more bicyclo[1.1.1]pentane units has been investigated by ascertaining how a variable substituent at a bridgehead position perturbs the geometry of a phenyl group at the opposite end of the molecule. We have analyzed the molecular structures of many bicyclo[1.1.1]pentane and [n]staffane derivatives of general formula Ph [C(CH(2))(3)C](n)-X (n = 1-5), as obtained from molecular orbital calculations at the HF/6-31G* and B3LYP/6-311++G** levels of theory. When n = 1, the structural variation of the benzene ring is controlled primarily by the long-range polar effect of X, with significant contributions from electronegativity and pi transfer effects. The capability of the bicyclo[1.1.1]pentane framework to transmit these short-range effects originates from the rather high electron density inside the cage and the hyperconjugative interactions occurring between substituent and framework. A set of at least two bicyclo[1.1.1]pentane units appears to be necessary to remove most of the electronegativity and pi-transfer effects. In higher [n]staffanes (n >or= 3), the very small variation of the benzene ring geometry is controlled entirely by the long-range polar effect of X. With charged groups and for n >or= 2, the potential energy of the ring deformation decreases linearly with n(-3). In Ph-C(CH(2))(3)C-X molecules, the relatively large deformation of the bicyclo[1.1.1]pentane cage is determined primarily by the electronegativity of X, similar to the electronegativity distortion of the benzene ring in Ph-X molecules. Transfer of pi electrons from substituent to cage or vice versa also plays a role in determining the cage deformation. PMID- 20356083 TI - Whence the energy term of the rate constant? AB - Insights into the causes of energy barriers to reactions are obtained from our E* model for hydrogen abstractions. Results of the model are in good agreement with all eight experimentally studied symmetrical reactions of the type X-H + (*)X --> X(*) + H-X. The E* energy is broken down into three components: energy needed to overcome triplet repulsion between the terminal Xs, energy needed to bring the H X bonds to their transition state distances, and energy gain by the resonance stabilization of delocalization of the odd electron over three atoms. The strength of the X-H bond is a minor factor. The conclusion that triplet repulsion is a major factor is supported by the London equation and by results of recent high level theoretical calculations. The E* model requires inputs of bond dissociation energies, bond lengths, and infrared stretching frequencies of X-H and X-X. Some reported failures of E* are shown to have been caused by use of input values subsequently found to be incorrect. PMID- 20356084 TI - Characterization of peptides released by in vitro digestion of pork meat. AB - The main objective of this work was to identify and characterize the peptides generated by simulated gastrointestinal digestion of pork meat (longissimus dorsi) by the sequential action of pepsin and pancreatin. The obtained hydrolysate was analyzed by liquid chromatography coupled to a quadrupole time-of flight mass spectrometer equipped with a nanoelectrospray ionization source (nano LC-ESI-MS/MS). Using this technique 51 different peptides were identified in the hydrolysate, corresponding to fragments of the main structural muscle proteins and some well-known sarcoplasmic proteins. To the best of our knowledge, this constitutes the highest number of peptides identified in pork meat digests. Peptide fragment size ranged from six to sixteen amino acids, being rich in proline residues and thus making them more resistant to further degradation by digestive enzymes. The present study constitutes a clear evidence of the extensive degradation that pork muscle proteins would undergo after gastrointestinal digestion, giving rise to a wide variety of short peptides. So, the use of in vitro digestion contributes to a better knowledge about the generation of peptides from diets with high protein quality. PMID- 20356085 TI - Closed nanocontainer enables thioketones to phosphoresce at room temperature in aqueous solution. AB - Thiocarbonyl compounds possess unusual photophysical properties: they fluoresce from S(2), phosphoresce from T(1) only at extremely low concentrations in solution at room temperature, have unit quantum yield of intersystem crossing from S(1) to T(1), undergo self-quenching at diffusion-controlled rates, and are quenched by ground-state oxygen leading to self-destruction. In this article, we are concerned with finding a new method to observe phosphorescence from thioketones at room temperature in aqueous solution at high concentrations. To achieve this goal, one needs to find ways to eliminate diffusion-limited self quenching and oxygen quenching. We present here a general strategy that has allowed us to record phopshorescence from a number of thioketones in aqueous solution at room temperature. The method involves encapsulation of thioketone molecules within a "closed nanocontainer" made up of two cavitand molecules known by its trivial name as octa acid. In these supramolecular complexes, despite two thiocarbonyl compounds being present in close proximity, no self-quenching occurs within the confined space due to curtailment of their rotational freedom. Although phosphorescence could also be observed when these thioketones are included in open containers, such as cucurbiturils and cyclodextrines, the closed container made up of octa acid is found to be the best medium to observe phosphorescence from thioketones whose excited state chemistry is essentially controlled by self-quenching. PMID- 20356086 TI - ProteomeCommons.org collaborative annotation and project management resource integrated with the Tranche repository. AB - ProteomeCommons.org has implemented a resource that incorporates concepts of Web 2.0 social networking for collaborative annotation of data sets placed in the Tranche repository. The annotation tools are part of a project management resource that is effective for individual laboratories or large distributed groups. The creation of the resource was motivated by the need for a way to encourage annotation of data sets with high accuracy and compliance rates. The system is designed to respond to the dynamic nature of research in an easy-to-use fashion through the use of a dynamic data model that does not inhibit the innovation that is important for basic research. Placing the annotation tool within a project manager allows annotation to occur over the life of the project and provides the security and monitoring capabilities needed for large or small collaborative projects. The resource effectively supports distributed groups of investigators working on common data sets and is available immediately at https://ProteomeCommons.org . In addition, a silver compliant data resource based on ProteomeCommons.org has been developed for cancer Biomedical Informatics Grid (caBIG) to allow much broader access to the annotations describing data sets in the Tranche repository. PMID- 20356087 TI - Infrared and electronic spectroscopy of benzene-ammonia cluster radical cations [C(6)H(6)(NH(3))(1,2)](+): observation of isolated and microsolvated sigma complexes. AB - We report infrared (IR) and electronic spectra of benzene-ammonia cluster radical cations [C(6)H(6)(NH(3))(n)](+) (n = 1 and 2) in the gas phase to explore cluster structures and chemical reactivity of the simplest aromatic radical cation with base (nucleophile) molecules. The electronic spectra in the visible region indicate that these cluster cations no longer have the benzene cation chromophore as a result of an intracluster reaction. Analyses of the IR spectra, on the basis quantum chemical calculations and the vibration-internal rotation analysis, reveal that both [C(6)H(6)(NH(3))(1,2)](+) form sigma-complex structures, in which the ammonia moiety is covalently bonded to the benzene moiety due to the intracluster nucleophilic addition. For [C(6)H(6)(NH(3))(2)](+), it is also shown that the second ammonia molecule solvates the sigma-complex core via a N-H...N hydrogen bond. Such sigma-complex structures are generally supposed to be a key intermediate of aromatic substitution reactions. The observed mass spectra and energetics calculations, however, show that [C(6)H(6)(NH(3))(n)](+) systems are inert for aromatic substitutions. The present experimental observations indicate the inherent stability of these sigma-complex structures, even though they do not show the aromatic substitution reactivity. PMID- 20356088 TI - Binding of pollutant aromatics on carbon nanotubes and graphite. AB - The semiempirical PM3 method with dispersive corrections (PM3-D) is used to predict the interaction energy of a number of aromatic pollutants with a graphene surface and with carbon nanotubes. It is found that the dispersive interactions are dominant in determining the magnitude of the interaction and that electron transfer between the adsorbate and the surface is small. Good agreement is found between the calculated interaction energies and the experimental affinities measured in an aqueous environment. PMID- 20356089 TI - Assessment of a novel scoring method based on solvent accessible surface area descriptors. AB - A novel scoring algorithm based on unique solvent accessible surface area (SASA) descriptors was comparatively evaluated for its database enrichment potential against the virtual screening (VS) methods GOLD and Glide. Several protein test cases, including adenosine deaminase and estrogen receptor alpha, were used for the evaluation. The structure-based VS method GOLD was used to generate the protein-ligand docking poses. These docking poses were then postprocessed with a protein-ligand interaction fingerprint metric. Next, the SASA descriptors were computed for each ligand and its respective protein in their bound/unbound states; a Bayesian model was learned with SASA descriptors and subsequently used to score the remaining ligands in the screening databases. Early database enrichments using SASA descriptors were found comparable or superior to those of GOLD and Glide. Moreover, SASA descriptors display an outstanding robustness to produce satisfactory early enrichments for a large variety of target classes. Based on these encouraging results, these novel topological descriptors constitute a valuable in silico tool in hit finding practices. PMID- 20356090 TI - Life cycle assessment of high-rate anaerobic treatment, microbial fuel cells, and microbial electrolysis cells. AB - Existing wastewater treatment options are generally perceived as energy intensive and environmentally unfriendly. Much attention has been focused on two new approaches in the past years, (i) microbial fuel cells and (ii) microbial electrolysis cells, which directly generate electrical current or chemical products, respectively, during wastewater treatment. These systems are commonly denominated as bioelectrochemical systems, and a multitude of claims have been made in the past regarding the environmental impact of these treatment options. However, an in-depth study backing these claims has not been performed. Here, we have conducted a life cycle assessment (LCA) to compare the environmental impact of three industrial wastewater treatment options, (i) anaerobic treatment with biogas generation, (ii) a microbial fuel cell treatment, with direct electricity generation, and (iii) a microbial electrolysis cell, with hydrogen peroxide production. Our analysis showed that a microbial fuel cell does not provide a significant environmental benefit relative to the "conventional" anaerobic treatment option. However, a microbial electrolysis cell provides significant environmental benefits through the displacement of chemical production by conventional means. Provided that the target conversion level of 1000 A.m(-3) can be met, the decrease in greenhouse gas emissions and other environmentally harmful emissions (e.g., aromatic hydrocarbons) of the microbial electrolysis cell will be a key driver for the development of an industrial standard for this technology. Evidently, this assessment is highly dependent on the underlying assumptions, such as the used reactor materials and target performance. This provides a challenge and an opportunity for researchers in the field to select and develop appropriate and environmentally benign materials of construction, as well as demonstrate the required 1000 A.m(-3) performance at pilot and full scale. PMID- 20356091 TI - Characterization of Enterococcus spp. from human and animal feces using 16S rRNA sequences, the esp gene, and PFGE for microbial source tracking in Korea. AB - Contamination from human and animal fecal waste is a primary cause of water pollution. Microbial source tracking (MST) may be a useful tool for high-quality environmental management and for assessing human health risks associated with water pollution. The goal of this study was to evaluate Enterococcus spp. as a target organism for MST. Thirty-four fecal samples were collected from five different sources (human, chicken, pig, cow, and goose) in South Korea. In total, 237 Enterococcus spp. were isolated from feces using membrane- Enterococcus indoxyl-beta-d-glucoside agar. The 16S rRNA gene and the whole genome were analyzed using nucleic acid sequencing and pulsed-field gel electrophoresis (PFGE), respectively. Both phylogenetic analysis and principal coordinate analysis using UniFrac were performed on the nucleic acid sequences of the 16S rRNA gene. According to P-tests from UniFrac, significant differences existed between Enterococcus spp. isolated from human feces and those from animal feces. In addition, we evaluated whether the esp gene of Enterococcus faecium could be a specific target for Enterococcus spp. isolated from human feces. Of 58 E. faecium isolates tested, only three were esp-positive. The specificity of the esp gene of E. faecium isolated from human feces was 100%, but the sensitivity was <10%. These results suggest that Enterococcus spp. have different molecular characteristics according to their fecal source and that these characteristics can be further identified by analyzing the esp gene and 16S rRNA sequences, whereas PFGE provides limited information on the fecal sources of Enterococcus spp. PMID- 20356092 TI - Organochlorine compounds and their metabolites in seven Icelandic seabird species - a comparative study. AB - The present study is designed to assess the occurrence of a few organochlorine contaminants and their metabolites in eggs of different marine bird species in Iceland, a country located in the sub-Arctic of the North-Western Atlantic. Previous investigations from e.g. Sweden and The Netherlands have shown some obvious differences in contaminant concentrations, including e.g. hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) in guillemot (Uria aalge) and other bird species. Eggs from seven marine bird species, Arctic tern (Sterna paradisaea), common eider (Somateria mollissima), guillemot, fulmar (Fulmarus glacialis), great black-backed gull (Larus marinus), lesser black-backed gull (Larus fuscus), and great skua (Stercorarius skua), that all breed in Iceland, were collected and analyzed for several persistent organic compounds and their metabolites. The contaminant levels varied between the species investigated. The highest concentrations were found in eggs from the great skua (18 and 23 microg/g l.w. of CB-153 and 4,4'-DDE, respectively). The concentration difference was generally 2 orders of magnitude higher in great skua for all organochlorine compounds analyzed with the exception of HCB. HCB did not vary as much between the seven species (ranging from 34 to 710 ng/g l.w). OH-PCB and MeSO(2)-PCB metabolites congener concentrations and patterns showed differences in metabolic capacity between bird species. Guillemot and great skua seem to distinguish themselves most from other species i.e. with the absence of 4-OH-CB187 and low relative levels of 4-OH-CB146 in guillemot and the low abundance of OH-PCBs in great skua. PMID- 20356093 TI - Aging of rubrene layers in Ni/rubrene heterostructures studied by magneto-optical Kerr effect spectroscopy. AB - Magneto-optical Kerr effect (MOKE) spectroscopy was applied to probe the aging of Ni/rubrene bilayers under ambient atmosphere. A comparison between the simulated MOKE spectra of the heterostructure and the experimental MOKE spectra recorded at several time intervals after the samples were exposed to the ambient atmosphere demonstrates that the organic layer undergoes slow oxidation. The Ni top layer was found to exhibit capping properties, reducing the rate of oxidation of the organic underlayer in comparison with single organic layers. PMID- 20356095 TI - Four-component domino reaction providing an easy access to multifunctionalized tricyclo[6.2.2.0(1,6)]dodecane derivatives. AB - A novel four-component domino reaction has been discovered. The reaction is easy to perform simply by mixing four common reactants and Cs(2)CO(3) in ethylene glycol under microwave heating. The reaction proceeds at fast rates and can be finished within 15-24 min, which makes workup convenient. Four stereogenic centers with one quaternary carbon-amino function have been controlled completely. The stereochemistry has been unequivocally determined by X-ray structural analysis. The resulting tricyclo[6.2.2.0(1,6)]dodecane derivatives are of importance for organic and medicinal research. PMID- 20356096 TI - Protein fluctuations as the possible origin of the thermal activation of rod photoreceptors in the dark. AB - Efficient retinal photoisomerization, signal transduction, and amplification contribute to single-photon electrical responses in vertebrates visual cells. However, spontaneous discrete electrical signals arising in the dark, with identical intensity and time profiles as those generated by genuine single photons (dark events), limit the potential capability of the rod visual system to discern single photons from thermal noise. It is accepted that the light and the thermal activation of the rod photoreceptor rhodopsin (Rho) triggers the light and the dark events, respectively. However the activation barrier for the dark events (80-110 kJ/mol) appears to be only half of the barrier for light-dependent activation of Rho (> or =180 kJ/mol). On the basis of these observations, it has been postulated that both processes should follow different pathways, but the molecular mechanism for the thermal activation process still remains an open question and subject of debate. Here, performing infrared difference spectroscopy measurements, we found that the -OH group of Thr118 from bovine Rho exhibits a slow but measurable hydrogen/deuterium exchange (HDX) under native conditions. Given the location of Thr118 in the X-ray structures, isolated from the aqueous phase and in steric contact with the buried retinal chromophore, we assume that a protein structural fluctuation must drive the retinal binding pocket (RBP) transiently open. We characterized the kinetics (rate and activation enthalpy) and thermodynamics (equilibrium constant and enthalpy) of this fluctuation from the global analysis of the HDX of Thr118-OH as a function of the temperature and pH. In parallel, using HPLC chromatography, we determined the kinetics of the thermal isomerization of the protonated 11-cis retinal in solution, as a model for retinal thermal isomerization in an open RBP. Finally, we propose a quantitative two-step model in which the dark activation of Rho is triggered by thermal isomerization of the retinal in a transiently opened RBP, which accurately reproduced both the experimental activation barrier and the rate of the dark events. We conclude that the absolute sensitivity threshold of our visual system is limited by structural fluctuations of the chromophore binding pocket rather than in the chromophore itself. PMID- 20356097 TI - Electrostatic-assembly-driven formation of micrometer-scale supramolecular sheets of (3-aminopropyl)triethoxysilane(APTES)-HAuCl4 and their subsequent transformation into stable APTES bilayer-capped gold nanoparticles through a thermal process. AB - In this letter, we demonstrate for the first time the electrostatically driven assembly of (3-aminopropyl)triethoxysilane (APTES) and HAuCl(4) in aqueous media into novel micrometer-scale supramolecular sheets and their subsequent transformation into small, stable APTES bilayer-capped gold nanoparticles through a thermal process. The nanoparticle formation mechanism is also discussed. PMID- 20356099 TI - Formation of thick, large-area nanoparticle superlattices in lithographically defined geometries. AB - Superlattices of colloidal nanocrystals hold the promise of new nanomaterials with tunable properties. The positioning and size of these structures are often poorly controlled after self-assembly from the solution phase, making studies of their properties difficult. We report the fabrication of approximately 100 layer thick, three-dimensional superlattices on a substrate with controlled lateral placement. This novel fabrication technique generates long-range order over the micrometer scale and controlled placement by employing lithographic patterning and microfluidic flow. PMID- 20356098 TI - A novel class of antihyperlipidemic agents with low density lipoprotein receptor up-regulation via the adaptor protein autosomal recessive hypercholesterolemia. AB - We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC(25) = 0.047 microM). Compound 39 showed no ACAT inhibitory activity even at 1 microM. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression. PMID- 20356100 TI - A stable, label-free optical interferometric biosensor based on TiO2 nanotube arrays. AB - Optical interferometry of a thin film array of titanium dioxide (TiO2) nanotubes allows the label-free sensing of rabbit immunoglobulin G (IgG). A protein A capture probe is used, which is immobilized on the inner pore walls of the nanotubes by electrostatic adsorption. Control experiments using IgG from chicken (which does not bind to protein A) confirms the specificity of the protein A modified TiO2 nanotube array sensor. The aqueous stability of the TiO2 nanotube array was examined and compared with porous silica (SiO2), a more extensively studied thin film optical biosensor. The TiO2 nanotube array is stable in the pH range 2 to 12, whereas the porous SiO2 sensor displays significant degradation at pH > 8. PMID- 20356101 TI - Diversity-oriented construction of highly substituted indolizinones. AB - Rapid generation of a small library of highly functionalized indolizonones was realized by exploiting three palladium-catalyzed cross-coupling reactions of 2 iodoindolizinones which in turn were readily accessed via sequential iodine mediated cyclization/1,2-shift reactions of propargylic alcohols. PMID- 20356094 TI - Fluorescence lifetime measurements and biological imaging. PMID- 20356102 TI - Intersublevel infrared photodetector with strain-free GaAs quantum dot pairs grown by high-temperature droplet epitaxy. AB - Normal incident photodetection at mid infrared spectral region is achieved using the intersublevel transitions from strain-free GaAs quantum dot pairs in Al(0.3)Ga(0.7)As matrix. The GaAs quantum dot pairs are fabricated by high temperature droplet epitaxy, through which zero strain quantum dot pairs are obtained from lattice matched materials. Photoluminescence, photoluminescence excitation optical spectroscopy, and visible-near-infrared photoconductivity measurement are carried out to study the electronic structure of the photodetector. Due to the intersublevel transitions from GaAs quantum dot pairs, a broadband photoresponse spectrum is observed from 3 to 8 microm with a full width at half-maximum of approximately 2.0 microm. PMID- 20356103 TI - Dithiodiolate ligands: group 4 complexes and application in lactide polymerization. AB - Dithiodiolate ligands were synthesized by reacting 1,2-ethanedithiol or 1,2 benzenedithiol with 2,2-bis(trifluoromethyl)oxirane, led selectively to mononuclear octahedral group 4 complexes of the type [{OSSO}M(OR)(2)], which features C(2) symmetry and fluxional behavior, and were highly active in the ring opening polymerization of rac- and L-lactide. PMID- 20356104 TI - Phosphorodiamidate-directed metalation of N-heterocycles using Mg- and Zn-TMP bases. AB - The strong directing ability of the N,N,N',N' tetramethyldiaminophosphorodiamidate group has been used to achieve selective metalations on various heterocycles such as pyridines, quinolines and quinoxalines with TMP-derived bases like TMPMgCl x LiCl, TMP(2)Mg x 2 LiCl, and TMP(2)Zn x 2 MgCl(2) x 2 LiCl. This protocol was applied in the synthesis of etoricoxib, talnetant and a P-selectin inhibitor. PMID- 20356105 TI - Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. PMID- 20356106 TI - Synthesis and structural analysis of a new class of azaspiro[3.3]heptanes as building blocks for medicinal chemistry. AB - Straightforward access toward previously unreported substituted, heterocyclic spiro[3.3]heptanes is disclosed. These spirocyclic systems may be considered as alternatives to 1,3-heteroatom-substituted cyclohexanes, which are otherwise insufficiently stable to allow their use in drug discovery. Conformational details are discussed on the basis of X-ray crystallographic structures. PMID- 20356108 TI - Organic-soluble antimicrobial silver nanoparticle-polymer composites in gram scale by one-pot synthesis. AB - We report a one-pot synthesis of silver nanoparticle-polymer composites (Ag-PNCs) in water by a novel finding involving the polycondensation of methoxybenzyl chlorides (MeO-BzCl) directly on Ag nanoparticle surfaces at room temperature, leading to highly soluble antimicrobial nanocomposites. The composites, which are soluble in a range of organic solvents, precipitate in the reaction vessel, making their separation simple. Solutions of the composites can be casted directly on substrates or made into freestanding films. The material was found to be stable for nearly 2 years. A range of substrates have been shown to become antibacterial by direct application of this material. The experiments were conducted with Ag-PNC-loaded filter paper strips and glass substrates. The samples were found to be antimicrobial (against Escerichia coli and Aspergillus niger). The simple one-pot approach of this kind to make organic-soluble antibacterial coatings could have wide implications. PMID- 20356109 TI - Electrostatically self-assembled nanocomposite reactive microspheres. AB - Nanocomposite reactive microspheres with diameters of approximately 1-5 mum were created via electrostatic self-assembly of aluminum and cupric oxide nanoparticles. The ability to utilize this novel approach of bottom-up assembly to create these reactive materials allows for the potential for a more intimate mixture between the two nanoreactants and, thus, an overall more energetic combustion process. Experiments with the self-assembled material demonstrate the ability to achieve ignition and sustain a combustion wave in rectangular microchannels, which does not occur with material having similar amounts of organics mixed via the traditional sonication method. PMID- 20356110 TI - Smart nanofibers with a photoresponsive surface for controlled release. AB - A novel photocontrolled "ON-OFF" release system for the alpha-cyclodextrin-5 fluorouracial (alpha-CD-5FU) prodrug, based on host-guest interaction on the photoresponsive and cross-linked nanofiber surface, was demonstrated. The nanofibers with a stimuli-responsive surface were electrospun from the block copolymer prepared via controlled radical polymerization, followed by surface modification via "Click Chemistry", and loading of the prodrug via host-guest interaction. PMID- 20356111 TI - Ultraviolet photodetector based on a MgZnO film grown by radio-frequency magnetron sputtering. AB - The metal-semiconductor-metal ultraviolet (UV) photodetector was fabricated on the Mg(0.47)Zn(0.53)O layer grown by radio-frequency magnetron cosputtering. The photodetector shows the peak response at 290 nm with a cutoff wavelength at 312 nm. It exhibits a very low dark current of about 3 pA at 5 V bias, and the UV visible rejection ratio (R = 290 nm/R = 400 nm) is more than 4 orders of magnitude. The transient response for the detector was measured, and it was found that the rise time is 10 ns and the fall time is 30 ns. The reason for the short response time is related to the Schottky structure. PMID- 20356112 TI - Surface deposition and phase behavior of oppositely charged polyion/surfactant ion complexes. 1. Cationic guar versus cationic hydroxyethylcellulose in mixtures with anionic surfactants. AB - Mixtures of cationic guar (cat-guar) or cationic hydroxyethylcellulose (cat-HEC) with the anionic surfactants sodium dodecyl sulfate or sodium lauryl ether-3 sulfate have been investigated by a wide range of complementary techniques (phase studies, turbidity measurements, dynamic light scattering, gel-swelling experiments, and in situ null ellipsometry), with the following objectives in mind: (1) to establish the relationship between the bulk phase behavior (precipitation and redissolution) of the polyion/surfactant ion complexes and formation/deposition of such complexes at silica surfaces and (2) to obtain molecular interpretations of the large, previously unresolved, quantitative differences between the various investigated mixtures. There were clear similarities, for each studied system, between the bulk phase behavior, gel swelling, and surface deposition on increasing surfactant concentration. This is because all phenomena reflect the polyion/surfactant ion binding isotherm: an initial binding step at a low critical association concentration (cac) of the surfactant and a second more-or-less cooperative binding step beginning at a second cac, the cac(2). The details of the interactions are system-specific, however, and cat-guar/surfactant mixtures generally had larger precipitation regions and gave rise to larger adsorbed amounts on silica compared to mixtures with cat-HEC of a similar charge density. The observed quantitative differences are attributed to a difference in the hydrophobicity of the polyions. For cat guar, the comparatively weak hydrophobic polyion/surfactant attraction is seen as a very gradual binding commencing at the cac(2) and continuing past the bulk critical micelle concentration of the surfactant, resulting in an unusually large phase-separation region. For cat-HEC, the dissolution of the precipitate takes place at lower surfactant concentrations because of a stronger hydrophobic interaction between the surfactant and the polyion. The results have implications for the successful design of oppositely charged polyelectrolyte/surfactant formulations for surface deposition applications. PMID- 20356113 TI - Design of highly oleophobic cellulose surfaces from structured silicon templates. AB - Structured silicon surfaces, possessing hierarchical porous characteristics consisting of micrometer-sized cavities superimposed upon a network of nanometer sized pillars or wires, have been fabricated by a plasma-etching process. These surfaces have superoleophobic properties, after being coated with fluorinated organic trichlorosilanes, on intrinsically oleophilic surfaces. By comparison with flat silicon surfaces, which are oleophilic, it has been demonstrated that a combination of low surface energy and the structured features of the plasma etched surface is essential to prevent oil from penetrating the surface cavities and thus induce the observed macroscopic superoleophobic phenomena with very low contact-angle hysteresis and low roll-off angles. The structured silicon surfaces were coated with cellulose nanocrystals using the polyelectrolyte multilayer technique. The cellulose surfaces prepared in this way were then coated with a monolayer of fluorinated trichlorosilanes. These porous cellulose films displayed highly nonwetting properties against a number of liquids with low surface tension, including alkanes such as hexadecane and decane. The wettability and chemical composition of the cellulose/silicon surfaces were characterized with contact-angle goniometry and X-ray photoelectron spectroscopy, respectively. The nano/microtexture features of the cellulose/silicon surfaces were also studied with field-emission scanning electron microscopy. The highly oleophobic structured cellulose surfaces are very interesting model surfaces for the development of biomimetic self-cleaning surfaces in a vast array of products, including green constructions, packaging materials, protection against environmental fouling, sports, and outdoor clothing, and microfluidic systems. PMID- 20356114 TI - New approach toward nanosized ferrous ferric oxide and Fe(3)O(4)-doped titanium dioxide photocatalysts. AB - In this article, ferrous ferric oxide and Fe(3)O(4)-doped titanium dioxide have been synthesized by a low-temperature sol-gel process. In particular, we studied the structural characteristics of newly synthesized photosensitive catalysts and their photocatalytic abilities under UV and visible light irradiation. The elemental composition, surface area, crystallinity, and morphology of synthesized catalysts were characterized by Fourier transformation infrared spectrophotometry, X-ray photoelectron spectroscopy, X-ray diffraction, and transmission electron microscopy with selected area electron diffraction and energy-dispersive X-ray spectroscopy. The UV-vis transmission, zeta-potential, and cytotoxicity of the synthesized catalysts are also discussed. It is anticipated that the synthesized ferrous ferric oxide arrays a prospective photocatalyst substitute for titanium dioxide. PMID- 20356115 TI - Single-step synthesis and structural study of mesoporous sulfated titania nanopowder by a controlled hydrolysis process. AB - An environmentally benign route for the single-step synthesis of mesoporous sulfated titania is described by a seeding method using titanium oxysulfate as the titania source. The hydrolysis was performed in the presence of NaOH and seed under constant-volume conditions around 98 degrees C. The XPS and DRIFT spectra show the existence of a bridged bidentate sulfate complex on the surface of titania. The elimination of sulfur on heat treatment showed a characteristic change in mesoporosity, specific surface area, and crystallinity of the material. The transformation of sulfated titania to anatase was incomplete at 900 degrees C, showing a delay in crystallization due to the presence of sulfur. Studies on the thermal stability of the sulfated titania showed that the material obtained can be used for various applications at temperatures below 300 degrees C. The ammonia-TPD and catalytic performance studies of the sulfated titania samples showed the presence of strong acid sites. PMID- 20356116 TI - Carbon nanotube reinforced polylactide-caprolactone copolymer: mechanical strengthening and interaction with human osteoblasts in vitro. AB - This study proposes the use of carbon nanotubes (CNTs) as reinforcement to enhance the mechanical properties of a polylactide-caprolactone copolymer (PLC) matrix. Biological interaction of PLC-CNT composites with human osteoblast cells is also investigated. Addition of 2 wt % CNT shows very uniform dispersion in the copolymer matrix, whereas 5 wt % CNT shows severe agglomeration and high porosity. PLC-2 wt % CNT composite shows an improvement in the mechanical properties with an increase in the elastic modulus by 100% and tensile strength by 160%, without any adverse effect on the ductility up to 240% elongation. An in vitro biocompatibility study on the composites shows an increase in the viability of human osteoblast cells compared to the PLC matrix, which is attributed to the combined effect of CNT content and surface roughness of the composite films. PMID- 20356117 TI - Electrochemical behavior of gold colloidal alkyl modified silicon surfaces. AB - Herein, we report on the production of nanoelectrode arrays by attaching colloidal gold on silicon-bound mixed self-assembled monolayers of TFA-protected alkenylthiol (C(11)-S-TFA) and undecylenic acid (acid). Effective modification of the surface, tethering of the nanoparticles, and the direct influence of the deprotected alkenylthiol (C(11)-SH) /acid ratio on the number of adherent particles were demonstrated using X-ray photoelectron spectroscopy, electrochemistry, and atomic force microscopy. Cyclic voltammetry showed that the enhancement of electron transfer to the silicon surface by the presence of nanoparticles is influenced by the number of tethered nanoparticles. PMID- 20356118 TI - High-sensitivity Raman scattering substrate based on Au/La(0.7)Sr(0.3)MnO(3) periodic arrays. AB - We have developed Au/La(0.7)Sr(0.3)MnO(3) (Au/LSMO) periodic arrays with tunable surface plasmon properties that can be used as novel surface-enhanced Raman scattering (SERS) substrates. The periodic arrays are created by electron beam lithography of LSMO resist and metal film deposition. The LSMO electron beam resist is unique in that it exhibits either positive or negative resist behaviors depending on the electron beam dosage. Interestingly, surface plasmon behavior of the arrays can be controlled by just changing the electron beam dosage when presented with a fixed design pattern. Scanning confocal microscopy and spectral microreflectometry have been adapted to directly demonstrate this unique behavior. Furthermore, we show that our novel Au/LSMO array can be used as a high sensitivity Raman scattering substrate. To illustrate this working principle, the Au/LSMO periodic array is applied to enhance the Raman scattering of a thin film containing 0.1 wt % poly-3-hexylthiophene (P3HT) in poly(methyl methacrylate) (PMMA). By controlling the geometry of the patterned substrate that exhibits gold surface plasmon near the excitation wavelength, we can enhance the intensity of Raman scattering of P3HT at 1350 cm(-1) up to 4 orders of magnitude as compared with previously generated planar Au substrates. PMID- 20356119 TI - Flexible nanofiber-reinforced aerogel (xerogel) synthesis, manufacture, and characterization. AB - Silica aerogels are sol-gel-derived materials consisting of interconnected nanoparticle building blocks that form an open and highly porous three dimensional silica network. Flexible aerogel films could have wide applications in various thermal insulation systems. However, aerogel thin films produced with a pure sol-gel process have inherent disadvantages, such as high fragility and moisture sensitivity, that hinder wider applications of these materials. We have developed synthesis and manufacturing methods to incorporate electrospun polyurethane nanofibers into the cast sol film prior to gelation of the silica based gel in order to reinforce the structure and overcome disadvantages such as high fragility and poor mechanical strength. In this method, a two-stage sol-gel process was employed: (1) acid-catalyzed tetraethyl orthosilicate hydrolysis and (2) base-catalyzed gelation. By precisely controlling the sol gelation kinetics with the amount of base present in the formulation, nanofibers were electrospun into the sol before the onset of the gelation process and uniformly embedded in the silica network. Nanofiber reinforcement did not alter the thermal conductivity and rendered the final composite film bendable and flexible. PMID- 20356120 TI - Electrospun nylon nanofibers as effective reinforcement to polyaniline membranes. AB - This research demonstrates that a nylon nanofiber (NNF) mat can be an effective mechanical reinforcement to polyaniline (PANI) thin films. Nanofibers of ca. 250 nm diameter were produced by electrospinning of a nylon 6 solution in formic acid. Scanning electron microscopy showed that the solution impregnation method utilized was effective to embed the nanofibers into the PANI matrix. The effectiveness of NNFs as a mechanical reinforcement of a PANI thin film was assessed via dynamic mechanical analysis in tension mode. The as-cast PANI films displayed a tensile dynamic modulus, E', of ca. 0.65 GPa at room temperature. Scanning in the temperature showed that the PANI film has a usage temperature of up to about 80 degrees C, with this being limited by its glass transition temperature, and over this temperature range, the elastic modulus was nearly independent of the temperature. On the other hand, the PANI-NNF composite displayed a significantly higher tensile modulus at room temperature (1.1 GPa) and its usage temperature was extended up to just over 200 degrees C, with this being limited by the melting transition of nylon 6 (at 220 degrees C). The results therefore showed that the NNF mat increased the usage temperature of PANI films over 100 degrees C, opening up applications for PANI membranes. PMID- 20356121 TI - Facile catalytic combustion of rice husk and burning temperature dependence of the ashes. AB - In this work, it was discovered and demonstrated that the combustion of rice husk is a catalytic process by the thermoanalytical technique. The catalyst involves the oxides of such transition metals as Mn, Fe, and Cu, which are mainly formed in the initial stage of rice husk combustion and remain in the rice husk ash as an impurity. Mn(2+) ions of various concentrations were reloaded into the HCl washed husk for cocombustion. As a result, the complete combustion temperature of the husk was decreased exponentially depending on the Mn(2+) concentration. By the facile Mn loading technique using a 0.5 M solution, the combustion temperature can be decreased by approximately 100 degrees C, and the resulting ashes themselves can be a good catalyst in the complete combustion of many other organic compounds. The physicochemical properties and amorphous structure of the ashes from both the raw and HCl-washed husks were found to be strongly dependent on the burning temperature. A decreased complete rice husk combustion temperature can be beneficial in preparing porous amorphous silica with high surface area, high densification, and small Si-O-Si band angles. PMID- 20356123 TI - A new rhodamine-based colorimetric cyanide chemosensor: convenient detecting procedure and high sensitivity and selectivity. AB - By applying an indirect strategy, a new rhodamine-based dye (I) was successfully developed as a colorimetric chemosensor for the sensitive detection of cyanide. In the presence of copper ions, the colorless solution of compound I changed to magenta; however, upon the addition of trace cyanide, the magenta color faded to colorless immediately, with a detection limit as low as 0.013 ppm (DeltaA = 0.054), much lower than the Maximum Contaminant Level for cyanide in drinking water (0.20 ppm) set by the US Environmental Protection Agency. Other anions, including Cl(-), I(-), IO(3)(-), SO(4)(2-), NO(2)(-), Br(-), H(2)PO(4)(-), F(-), SCN(-), HSO(4)(-), and ClO(4)(-), had nearly no influence on the probing behavior of dye I toward cyanide. PMID- 20356122 TI - Poly(methyl methacrylate) grafting onto stainless steel surfaces: application to drug-eluting stents. AB - Drug-eluting stents (DESs) have been associated with adverse clinical effects. Moreover, recent publications have shown that the coating of DESs suffers from defects. The purpose of this contribution is to examine a three-step process for surface modification as a means of improving the durability of DESs. In the first step, 4-(2-bromoethyl)benzenediazonium tetrafluoroborate was electrografted onto a stainless steel (SS) stent. X-ray photoelectron spectroscopy (XPS) of the modified stent confirmed the formation of the organic layer. In the second step, methyl methacrylate was polymerized onto the grafted surface by atom-transfer radical polymerization. XPS, electrochemical impedance spectroscopy, and contact angle measurements were used to characterize the polymer brushes. The last step involved spray-coating of the stent with a drug-in-polymer matrix [poly(n-butyl methacrylate)/poly(ethylene-co-vinyl acetate) + paclitaxel]. Scanning electron microscopy confirmed the considerably improved durability of the drug-in-polymer matrix. Bare controls showed greater cracking and delamination of the coating than did the two-step modified stents after incubation under physiological (37 degrees C) and accelerated (60 degrees C) conditions. Finally, paclitaxel controlled release from the modified SS DESs was moderate compared with that of nontreated samples. In conclusion, the proposed method significantly improves the durability of drug-in-polymer matrixes on a SS DESs. PMID- 20356124 TI - Supercapacitive properties of PEDOT and carbon colloidal microspheres. AB - The synthesis and characterization of a new PEDOT-carbon composite prepared using a microporous carbon template are described. The electrochemical behavior of this composite, as well as that of three other colloidal materials-PEDOT-silica, PEDOT, and microporous carbon particles-is investigated with respect to their suitability as electrode materials in supercapacitors. This was accomplished by a combination of cyclic voltammetry and galvanostatic charge/discharge cycles. It was found that the PEDOT-silica composite had the lowest specific capacitance of the four materials (ca. 60 F g(-1)) and also the worst retention of the capacitance at high scan rates. In the case of pure PEDOT, microporous carbon, or PEDOT-carbon microspheres, the specific capacitances of the materials were dramatically higher (C(M) = 115, 109, and 106 F g(-1), respectively). These values are higher than those of either unstructured electropolymerized PEDOT or commercially available high-surface-area carbon. The pure PEDOT materials retained this high capacitive behavior even at faster scan rates, although the capacitance of the carbon and PEDOT-carbon microspheres dropped substantially. These results are interpreted in the context of the local microstructure of the individual colloidal particles, as well as the overall film morphology. The morphologies of both the individual particles and the electrode films were investigated by field-emission scanning electron microscopy. Due to the monodisperse nature of the microspheres, films composed of these materials necessarily possess an interconnected network of interstitial pores that allow for facile ionic diffusion. This allows for more penetration of the conjugated polymer by the ionic electrolyte and therefore higher capacitances relative to the bulk materials. These results demonstrate the feasibility of utilizing monodisperse colloidal microparticles containing conjugated polymers as electrode materials for high-energy and high-power-density supercapacitors. PMID- 20356125 TI - Novel approach for the assembly of highly efficient SERS substrates. AB - In this paper we present the properties of surface-enhanced Raman scattering (SERS) active substrates elaborated by a low-cost approach. Our methodology relying on capillary assembly and soft lithography allows us to generate periodic two-dimensional (2D) matrixes of 100 nm gold nanoparticle patterns in a very precise, cost-efficient, and large-scale manner. For this study, we assembled nanoparticle aggregates of different sizes (one to six particles) in order to determine the influence of the aggregation on the local electric field enhancement. We further demonstrate that this substrate is greatly efficient not only for SERS but also in metal-enhanced fluorescence (MEF) for local enhancement of conventional fluorescence. PMID- 20356126 TI - Silver nanodesert rose as a substrate for surface-enhanced Raman spectroscopy. AB - Silver galvanic displacement on silicon has been employed to produce large-area reproducible substrates, with morphology similar to that of the natural desert rose but on the micrometer scale. The process is based on an extremely simple wet chemistry approach using only AgF and KF, as silver and fluoride sources. A key element is the absence of HF in the deposition solution, which has been commonly used in previous silver galvanic displacement processes. The new process affords a higher degree of control in the redox reaction than those reported previously. The structures formed in this manner possess a large area-to-volume ratio with a high density of rough silver flakes uniformly distributed across the substrate. The silver morphology on the nanometer scale is shown to provide an excellent platform for surface-enhanced Raman spectroscopy (SERS), yielding detection levels for trans-1,2-bis(4-pyridyl)ethylene, 4-mercaptopyridine, and Rhodamine 6G in solution down to ppb, ppt, and ppq limits, respectively. The SERS reproducibility on the substrate was verified by monitoring the signal intensity variations across the sample. The simplicity of the substrate fabrication process, as well as the excellent uniformity, opens up opportunities for the quantitative and in-field chemical trace analysis using these substrates. PMID- 20356128 TI - Hierarchical multifunctional composites by conformally coating aligned carbon nanotube arrays with conducting polymer. AB - A novel method for the fabrication of carbon nanotube (CNT)-conducting polymer composites is demonstrated by conformally coating extremely high aspect ratio vertically aligned-CNT (A-CNT) arrays with conducting polymer via oxidative chemical vapor deposition (oCVD). A mechanical densification technique is employed that allows the spacing of the A-CNTs to be controlled, yielding a range of inter-CNT distances between 20 and 70 nm. Using this morphology control, oCVD is shown to conformally coat 8-nm-diameter CNTs having array heights up to 1 mm (an aspect ratio of 10(5)) at all inter-CNT spacings. Three phase CNT-conducting polymer nanocomposites are then fabricated by introducing an insulating epoxy via capillary-driven wetting. CNT morphology is maintained during processing, allowing quantification of direction-dependent (nonisotropic) composite properties. Electrical conductivity occurs primarily along the CNT axial direction, such that the conformal conducting polymer has little effect on the activation energy required for charge conduction. In contrast, the conducting polymer coating enhanced the conductivity in the radial direction by lowering the activation energy required for the creation of mobile charge carriers, in agreement with variable-range-hopping models. The fabrication strategy introduced here can be used to create many multifunctional materials and devices (e.g., direction-tailorable hydrophobic and highly conducting materials), including a new four-phase advanced fiber composite architecture. PMID- 20356127 TI - Antimicrobial activities and cellular responses to natural silicate clays and derivatives modified by cationic alkylamine salts. AB - Nanometer-scale silicate platelet (NSP) materials were previously developed by increasing the interlayer space and exfoliation of layered silicate clays such as montmorillonite and synthetic fluorinated mica by the process of polyamine exfoliation. In this study, the antibacterial activity and cytotoxicity of these nanometer-scale silicate clays were evaluated. The derivatives of NSP (NSP-S) which were modified by C18-fatty amine salts via ionic exchange association exhibited the highest antibacterial activity in the aqueous state among all clays. The high antibacterial activity, however, was accompanied by elevated cytotoxicity. The variations of cell surface markers (CD29 and CD44) and type I collagen expression of fibroblasts treated with the clays were measured to clarify the mechanism of the silicate-induced cytotoxicity. The signal transduction pathway involved the downregulation of extracellular-signal regulated kinase (ERK), which appeared to participate in silicate-induced cytotoxicity. This study helped to understand the antibacterial potential of NSP and the interaction of natural and modified clays with cellular activities. PMID- 20356129 TI - Acid-functionalized polysilsesquioxane-nafion composite membranes with high proton conductivity and enhanced selectivity. AB - A series of new Nafion-based composite membranes have been prepared via an in situ sol-gel reaction of 3-(trihydroxylsilyl)propane-1-sulfonic acid and solution casting method. The morphological structure, ion-exchange capacity, water uptake, proton conductivity, and methanol permeability of the resulting composite membranes have been extensively investigated as functions of the content of sulfopropylated polysilsesquioxane filler, temperature, and relative humidity. Unlike the conventional Nafion/silica composites, the prepared membranes exhibit an increased water uptake and associated enhancement in proton conductivity compared to unmodified Nafion. In particular, considerably high proton conductivities at 80 and 120 degrees C under 30% relative humidity have been demonstrated in the composite membranes, which are over 2 times greater than that of Nafion. In addition to a remarkable improvement in proton conductivity, the composite membranes display lower methanol permeability and superior electrochemical selectivities in comparison to the pure Nafion membrane. These unique properties could be exclusively credited to the presence of pendant sulfonic acid groups in the filler, which provides fairly continuous proton conducting pathways between filler and matrix in the composite membranes and thus facilitates the proton transport without the anticipated trade-off between conductivity and selectivity. This work opens new opportunities of tailoring the properties of Nafion-the benchmark fuel cell membrane-to obviate its limitations and enhance the conductive properties at high temperature/low humidity and in direct methanol fuel cells. PMID- 20356130 TI - Unconventional lithography for hierarchical micro-/nanostructure arrays with well aligned 1D crystalline nanostructures: design and creation based on the colloidal monolayer. AB - We have developed a strategy for designing and fabricating hierarchical micro /nanostructured arrays based on the combination of a colloidal monolayer substrate and the pulsed laser deposition (PLD) process. In this approach, microstructures are provided by the colloidal monolayer and can be tuned by changing colloidal monolayer periodicities, while crystalline nanostructures are supplied by PLD and can be controlled by PLD experiment parameters (e.g., ambient gas pressure). In comparison with the traditional lithography techniques, the proposed method has the obvious advantage of low cost. More importantly, the complicated hierarchical micro-/nanostructure arrays obtained by the present strategy cannot easily be designed and synthesized by traditional lithography techniques. This fact suggests that the proposed method can be a quite powerful alternative to fabricate complicated hierarchical arrays by complementing the weakness of traditional lithographic routes. In addition to these, the strategy also features uniform surface morphology, room-temperature reaction, and pure sample surfaces that are highly valuable to build a new generation of microdevices or nanodevices in nanophotonics, energy storage, etc. on the basis of these special hierarchical micro-/nanostructured arrays. PMID- 20356131 TI - Digital control of SiO(2)-TiO(2) mixed-metal oxides by pulsed PECVD. AB - Pulsed plasma enhanced chemical vapor deposition (PECVD) was used to deliver digital control of SiO(2), TiO(2), and SiO(2)-TiO(2) composites at room temperature. Alloy formation was investigated by maintaining constant delivery of TiCl(4) while varying the SiCl(4) flow. Film composition was assessed by spectroscopic ellipsometry, XPS, and FTIR. It is shown that the alloy composition and refractive index can be tuned continuously over a broad range using pulsed PECVD. The two precursors were found to be highly compatible, with the alloy growth rate simply reflecting the sum of the contributions from the two individual precursors. Digital control over both thickness and composition was demonstrated through the production of antireflection (AR) coatings for crystalline silicon. AR coatings were synthesized on the basis of optimized designs, and in each case the measured optical performance was found to be in excellent agreement with model predictions. The average reflectance across the visible spectrum was reduced from 39% for uncoated wafers to 2.5% for the three layer AR coating. PMID- 20356133 TI - Effect of particle hardness on the penetration behavior of fabrics intercalated with dry particles and concentrated particle-fluid suspensions. AB - The penetration behavior of Kevlar fabric intercalated with dry particles and shear thickening fluids (STF), highly concentrated fluid-particle suspensions, is presented. In particular, the role of particle hardness is explored by comparing fabric treatments containing SiO(2) particles, which are significantly harder than Kevlar, to treatments containing softer poly(methyl methacrylate) (PMMA) particles. The fabric testing includes yarn pull-out, quasi-static spike puncture, and ballistic penetration resistance, performed on single fabric layers. It was found that both dry particle and STF treatments resulted in improvements in fabric properties relative to neat or poly(ethylene glycol) (PEG) treated fabrics. On comparison of treatments with different particle hardness, the SiO(2) materials performed better in all tests than comparable PMMA materials, although the SiO(2) treatments caused yarn failure in pull-out testing, reducing the total pull-out energy. In addition, resistance to yarn pull out was found to be substantially higher for STF-treated fabrics than for dry particle treated fabrics. However, both dry particle addition and STF treatments exhibited comparable enhancements in puncture and ballistic resistance. These observations suggest that viscous stress transfer, friction, and physical entrainment of hard particles into filaments contribute to the demonstrated improvements in the properties of protective fabrics treated with shear thickening fluids. PMID- 20356132 TI - Micropatterning of proteins and mammalian cells on indium tin oxide. AB - This paper describes a novel surface engineering approach that combines oxygen plasma treatment and electrochemical activation to create micropatterned cocultures on indium tin oxide (ITO) substrates. In this approach, photoresist was patterned onto an ITO substrate modified with poly(ethylene) glycol (PEG) silane. The photoresist served as a stencil during exposure of the surface to oxygen plasma. Upon incubation with collagen (I) solution and removal of the photoresist, the ITO substrate contained collagen regions surrounded by nonfouling PEG silane. Chemical analysis carried out with time-of-flight secondary ion mass spectrometry (ToF-SIMS) at different stages in micropatterned construction verified removal of PEG-silane during oxygen plasma and presence of collagen and PEG molecules on the same surface. Imaging ellipsometry and atomic force microscopy (AFM) were employed to further investigate micropatterned ITO surfaces. Biological application of this micropatterning strategy was demonstrated through selective attachment of mammalian cells on the ITO substrate. Importantly, after seeding the first cell type, the ITO surfaces could be activated by applying negative voltage (-1.4 V vs Ag/AgCl). This resulted in removal of nonfouling PEG layer and allowed to attach another cell type onto the same surface and to create micropatterned cocultures. Micropatterned cocultures of primary hepatocytes and fibroblasts created by this strategy remained functional after 9 days as verified by analysis of hepatic albumin. The novel surface engineering strategy described here may be used to pattern multiple cell types on an optically transparent and conductive substrate and is envisioned to have applications in tissue engineering and biosensing. PMID- 20356134 TI - Facile approach in fabricating superhydrophobic and superoleophilic surface for water and oil mixture separation. AB - Metal copper mesh with superhydrophobic and superoleophilic surface had been successfully fabricated via a facile solution-immersion process. The hierarchical structure was prepared on the commercial copper mesh surface by etching with the nitric acid. After being modified by 1-hexadecanethiol (HDT), the as-prepared mesh indicated both superhydrophobic and superoleophilic property simultaneously. This as-prepared metal mesh could then be applied for oil and water mixture separation. The unusual wettability of the as-prepared mesh was stable in corrosive conditions, such as acidic, basic, and salt solutions. The solution immersion method was simple, time-saving, and inexpensive and therefore exhibited great potential application. PMID- 20356135 TI - Early detection of steel corrosion via "turn-on" fluorescence in smart epoxy coatings. AB - In the present work, we describe the successful application of spiro[1H-isoindole 1,9'-[9H]xanthen]-3(2H)-one, 3',6'-bis(diethylamino)-2-[(1 methylethylidene)amino] ("FD1") as a smart indicator in epoxy-based coatings for the early detection of steel corrosion. The FD1 indicator was used for epoxy based coatings on steel for its desirable property of "turn-on" fluorescence upon forming a complex with ferric ions produced at the anodic site during steel corrosion and because it does not prematurely fluoresce when mixed with the coating precursors (i.e., epoxy resin and amine). This indicator, after incorporation into a filled epoxy coating at a concentration as low as 0.5 wt %, was observed to become fluorescent in areas where corrosion started before any obvious sign of metal damage was observable. FD1 fluorescence was apparent both in areas around a scribed portion of the coating where the metal was exposed and in undercoating corrosion, where the coating surface was intact. This nondestructive method of early corrosion detection can help signal when maintenance is needed before the metal suffers serious damage. PMID- 20356136 TI - Flame synthesis of nanosized Cu-Ce-O, Ni-Ce-O, and Fe-Ce-O catalysts for the water-gas shift (WGS) reaction. AB - A flame synthesis method has been used to prepare nanosized, high-surface-area Cu Ce-O, Ni-Ce-O, and Fe-Ce-O catalysts from aqueous solutions of metal acetate precursors. The particles were formed by vaporization of the precursors followed by reaction and then gas to particle conversion. The specific surface areas of the synthesized powders ranged from 127 to 163 m(2)/g. High-resolution transmission electron microscope imaging showed that the particle diameters for the ceria materials are in the range of 3-10 nm, and a thin layer of amorphous material was observed on the surface of the particles. The presence and surface enrichment of the transition-metal oxides (CuO, NiO, and Fe(2)O(3)) on the ceria particles were detected using X-ray photoelectron spectroscopy. Electron energy loss spectroscopic studies suggest the formation of a core-shell structure in the as-prepared particles. Extended X-ray absorption fine structure studies suggest that the dopants in all M-Ce-O systems are almost isostructural with their oxide counterparts, indicating the doping materials form separate oxide phases (CuO, Fe(2)O(3), NiO) within the host matrix (CeO(2)). Etching results confirm that most of the transition-metal oxides are present on the surface of CeO(2), easily dissolved by nitric acid. The performance of the flame-synthesized catalysts was examined toward water-gas shift (WGS) activity for fuel processing applications. The WGS activity of metal ceria catalysts decreases in the order Cu-Ce-O > Ni-Ce O > Fe-Ce-O > CeO(2) with a feed mixture having a hydrogen to carbon monoxide (H(2)/CO) ratio of 1. There was no methane formation for these catalysts under the tested conditions. PMID- 20356137 TI - Surface chemical modification of poly(dimethylsiloxane)-based biomimetic materials: oil-repellent surfaces. AB - The oil-repellent performance of a poly(dimethylsiloxane)-based biomimetic replica (PDMS-replica) was tuned by modifying its surface chemical composition. PDMS-replica possessing a complementary combination of hierarchical roughness and mixed -CF(3) and -SiCH(3) terminal functionality was prepared in the presence of a surface-modifying agent, using nanocasting based on soft lithography. PDMS replica showed superhydrophobicity and enhanced oil repellency, theta(oil) approximately 86 degrees . PDMS-replica was further modified with silica nanoparticles followed by chemical vapor deposition of (heptadecafluoro-1,1,2,2 tetrahydrodecyl)trichlorosilane. The -CF(3) terminal, silica-modified PDMS replica (i.e., PDMS-replica(silica/CF(3))) showed both superhydrophobic and high oil-repellent properties (advancing theta(oil) approximately 120 degrees ). During the process of each chemical transformation, the surface pattern present on PDMS-replica was preserved and monitored using scanning electron microscopy. Surface chemical compositions of PDMS-replica and PDMS-replica(silica/CF(3)) were determined using X-ray photoelectron spectroscopy. Understanding the extent of adhesion on a biomimetic replica possessing different surface chemical compositions and roughness would provide fundamental information for various applications. PMID- 20356138 TI - Nanoscale patterning by UV nanoimprint lithography using an organometallic resist. AB - This paper presents the fabrication of poly(ferrocenylmethylphenylsilane) (PFMPS) patterns by step-and-flash imprint lithography for use as high-contrast etch masks in dry etch processes. PFMPS was spin-coated onto a resist template made by UV nanoimprint lithography to create a reactive ion etch resist layer with a thickness variation corresponding to the imprinted pattern. Etching back the excess of PFMPS by argon sputtering revealed the imprinted organic resist material, which was subsequently removed by oxygen plasma. PFMPS lines down to 30 nm were obtained after removal of the organic resist by oxygen plasma. Because PFMPS contains iron and silicon atoms in its main chain, it possesses a high resistance to oxygen reactive ion etching and, e.g., CHF(3)/O(2) or SF(6)/O(2) reactive ion etch processes. PFMPS patterns formed after imprinting were subsequently transferred into the underlying silicon substrate, and etch rates of 300 nm/min into Si and around 1 nm/min into the PFMPS layer were achieved, resulting in an etch contrast of approximately 300. PMID- 20356139 TI - ARGET ATRP for versatile grafting of cellulose using various monomers. AB - In recent years, cellulose-based materials have attracted significant attention. To broaden the application areas for cellulose, polymers are often grafted to/from the surface to modify its properties. This study applies ARGET (activators regenerated by electron transfer) ATRP (atom transfer radical polymerization) when straightforwardly grafting methyl methacrylate (MMA), styrene (St), and glycidyl methacrylate (GMA) from cellulose in the form of conventional filter paper in the presence of a sacrificial initiator. The free polymer, formed from the free initiator in parallel to the grafting, was characterized by (1)H NMR and SEC, showing that sufficient control is achieved. However, the analyses also indicated that the propagation from the surface cannot be neglected compared to the propagation of the free polymer at higher targeted molecular weights, which is an assumption often made. The grafted filter papers were evaluated with FT-IR, suggesting that the amount of polymer on the surface increased with increasing monomer conversion, which the FE-SEM micrographs of the substrates also demonstrated. Water contact angle (CA) measurements implied that covering layers of PMMA and PS were formed on the cellulose substrate, making the surface hydrophobic, in spite of low DPs. The CA of the PGMA-grafted filter papers revealed that, by utilizing either aprotic or protic solvents when washing the substrates, it was possible to either preserve or hydrolyze the epoxy groups. Independent of the solvent used, all grafted filter papers were essentially colorless after the washing procedure because of the low amount of copper required when performing ARGET ATRP. Nevertheless, surface modification of cellulose via ARGET ATRP truly facilitates the manufacturing since no thorough freeze-thaw degassing procedures are required. PMID- 20356140 TI - Enhanced charge transport in polymer thin-film transistors prepared by contact film transfer method. AB - The charge-carrier transport in the structures formed at the surface of various conjugated polymer films is investigated by constructing organic thin-film transistors using a novel and simple contact film transfer method. Thin-film transistors prepared by this transfer process have higher field-effect mobility values compared with conventional spin-coated devices for all the studied polymers. In contrast to previous reports, the hole mobility in regioregular poly(3-alkylthiophene)s does not depend on the length of the alkyl chain when the contact film transfer method is used. These results suggest that the thiophene rings adopt a highly ordered edge-on orientation and strong interchain pi-pi interactions spontaneously form at the polymer/air interface during the spin coating. PMID- 20356141 TI - Porphyrin-kaolinite as efficient catalyst for oxidation reactions. AB - The preparation, characterization, and application in oxidation reactions of new biomimetic catalysts are reported. Brazilian Sao Simao kaolinite clay has been functionalized with [meso-tetrakis(pentafluorophenyl)porphinato]iron(III), Fe(TPFPP). To obtain the functionalized clay, the natural clay was purified by dispersion-sedimentation, expanded by insertion of dimethyl sulfoxide (DMSO), and functionalized with amino groups by substitution of DMSO with ethanolamine. These previous steps allowed clay functionalization with Fe(TPFPP), leading to a layered material with a basal spacing of 10.73 A. Clay functionalization with the porphyrin was confirmed by formation of the secondary amine, as demonstrated by FTIR bands at 3500-3700 cm(-1). UV-vis spectroscopy revealed a red shift in the Soret band of the iron porphyrin in the functionalized material as compared to the parent iron porphyrin catalyst in solution, indicating Fe(III)P --> Fe(II)P reduction. The catalytic performance of the functionalized clay was evaluated in the epoxidation of cyclooctene, with complete selectivity for the epoxide (100% epoxide yield), and ketonization of cyclohexane, cyclohexanone being the major product. The novel catalyst was also evaluated in the Baeyer-Villiger (BV) oxidation of cyclohexanone, with 85% conversion of cyclohexanone in epsilon caprolactone, with total selectivity to epsilon-caprolactone. PMID- 20356142 TI - The molecularly controlled semiconductor resistor: how does it work? AB - We examine the current response of molecularly controlled semiconductor devices to the presence of weakly interacting analytes. We evaluate the response of two types of devices, a silicon oxide coated silicon device and a GaAs/AlGaAs device, both coated with aliphatic chains and exposed to the same set of analytes. By comparing the device electrical response with contact potential difference and surface photovoltage measurements, we show that there are two mechanisms that may affect the underlying substrate, namely, formation of layers with a net dipolar moment and molecular interaction with surface states. We find that whereas the Si device response is mostly correlated to the analyte dipole, the GaAs device response is mostly correlated to interactions with surface states. Existence of a silicon oxide layer, whether native on the Si or deliberately grown on the GaAs, eliminates analyte interaction with the surface states. PMID- 20356143 TI - LbL fabricated poly(styrene sulfonate)/TiO(2) multilayer thin films for environmental applications. AB - Fabrication of multilayer ultrathin composite films composed of nanosized titanium dioxide particles (P25, Degussa) and polyelectrolytes (PELs), such as poly(allyl amine hydrochloride) (PAH) and poly(styrene sulfonate sodium salt) (PSS), on glass substrates using the layer-by-layer (LbL) assembly technique and its potential application for the photodegradation of rhodamine B under ultraviolet (UV) irradiation has been reported. The polyelectrolytes and TiO(2) were deposited on glass substrates at pH 2.5 and the growth of the multilayers was studied using UV/vis spectrophotometer. Thickness measurements of the films showed a linear increase in film thickness with increase in number of bilayers. The surface microstructure of the thin films was characterized by field emission scanning electron microscope. The ability of the catalysts immobilized by this technique was compared with TiO(2) films prepared by drop casting and spin coating methods. Comparison has been made in terms of film stability and photodegradation of rhodamine B. Process variables such as the effect of surface area of the multilayers, number of bilayers, and initial dye concentration on photodegradation of rhodamine B were studied. Degradation efficiency increased with increase in number of catalysts (total surface area) and bilayers. Kinetics analysis indicated that the photodegradation rates follow first order kinetics. Under maximum loading of TiO(2), with five catalyst slides having 20 bilayers of polyelectrolyte/TiO(2) on each, 100 mL of 10 mg/L dye solution could be degraded completely in 4 h. The same slides could be reused with the same efficiency for several cycles. This study demonstrates that nanoparticles can be used in wastewater treatment using a simple immobilization technique. This makes the process an attractive option for scale up. PMID- 20356144 TI - Morphology control of cerium oxide particles synthesized via a supercritical solvothermal method. AB - Rod and sphere-like CeO(2) particles were obtained via a supercritical solvothermal method using CeCl(3).7H(2)O and Ce(NO(3))(3).6H(2)O as cerium sources in ethanol and methanol at 400 degrees C for 15 min followed by calcination in air. The rodlike particles were 200-400 nm in diameter and 1-2 mum in length. The spherical particles were 300-500 nm in diameter. The as-prepared rodlike particles using CeCl(3).7H(2)O consisted of mixtures of Ce(OH)(3) and Ce(CH(3)COO)(3) and were converted to rodlike CeO(2) by calcination in air at 500 degrees C. In contrast, the spherical particles prepared using Ce(NO(3))(3).6H(2)O consisted of fluorite-structured CeO(2). The possible formation mechanism was discussed on the basis of the effect of reaction time on the morphology at 400 degrees C. The rod- and spherelike CeO(2) particles exhibited strong UV absorption below 400 nm, and the absorbance edges extend to nearly 500 nm. The rod- and spherelike CeO(2) particles exhibited near-UV emission at 360 nm and blue emission at 465 nm with higher emission intensity compared to the commercial CeO(2) sample. PMID- 20356145 TI - Direct assembly of photoresponsive C(60)-gold nanoparticle hybrid films. PMID- 20356146 TI - Polymer bulk heterojunction photovoltaic devices with multilayer structures prepared by thermal lamination. PMID- 20356147 TI - A novel example of molecular hydrogen generation from formic Acid at visible light-responsive photocatalyst. PMID- 20356148 TI - Nanoscale patterning of organic monolayers by catalytic stamp lithography: scope and limitations. AB - Developing a method to pattern organic molecules, particularly on the sub-100-nm scale, is of wide interest in current nanoscience for a broad range of technological applications. Because of the efficiency and simplicity of soft lithography, here we describe in detail the process for synthesizing and applying catalytic stamp lithography, a process that can easily produce sub-100-nm patterns on surfaces; in this work, the approach is demonstrated on silicon. Catalytic stamps were fabricated through a two-step procedure in which the nanoscale pattern of catalysts is produced via a self-assembled block-copolymer templated synthesis of metallic nanostructures on SiO(x)/Si supports, followed by the production of the poly(dimethylsiloxane) (PDMS) stamp on top of the as patterned metals. Simply peeling off the as-formed PDMS stamp removes the metallic nanostructures, leading to the functional stamp. Two different patterns, pseudohexagonal and linear Pt nanoarrays, were produced from a single block copolymer, PS(125000)-b-P2VP(58500), by controlling the morphology of thin-film templates through tetrahydrofuran vapor annealing. When terminal alkenes, alkynes, or aldehydes with different functionalities were used as molecular inks, these Pt nanopatterns on catalytic stamps were translated into corresponding molecular arrays on Si(111)-H and Si(100)-H(x) surfaces because catalytic hydrosilylation took place exclusively underneath patterned Pt nanostructures. With this straightforward approach, the resolution limit of conventional microcontact printing (approximately 100 nm) could be downsized to a sub-20-nm scale, while maintaining the advantages of stamp-based patterning (i.e., large area, high-throughput capabilities and low cost). PMID- 20356149 TI - Photoemission spectroscopy and atomic force microscopy investigation of vapor phase codeposited silver/poly(3-hexylthiophene) composites. AB - Nanocomposite matrices of silver/poly(3-hexylthiophene) (P3HT) were prepared in ultrahigh vacuum through vapor-phase codeposition. Change in microstructure, chemical nature, and electronic properties with increasing filler (Ag) content were investigated using in situ XPS and UPS, and ambient AFM. At least two chemical binding states occur between Ag nanoparticles and sulfur in P3HT at the immediate contact layer, but no evidence of interaction between Ag and carbon (in P3HT) was found. AFM images reveal a change in Ag nanoparticles size with concentration which modifies the microstructure and the average roughness of the surface. Under codeposition, P3HT largely retains its conjugated structures, which is evidenced by the similar XPS and UPS spectra to those of P3HT films deposited on other substrates. We demonstrate here that the magnitude of the barrier height for hole injection (epsilon(v)(F)) and the position of the highest occupied band edge (HOB) with respect to the Fermi level of Ag may be controlled and changed by adjusting the metal (Ag) content in the composite. Furthermore, UPS reveals distinct features related to the C 2p (sigma states) in the 5-12 eV regions, indicating the presence of ordered P3HT, which is different from solution processed films. PMID- 20356150 TI - Facile fabrication of diblock methoxy poly(ethylene glycol)-poly(tetramethylene carbonate) and its self-assembled micelles as drug carriers. AB - AB type diblock methoxy poly(ethylene glycol)-b-poly(tetramethylene carbonate) (mPEG-PTeMC) copolymers were designed for the first time and used as carriers for the sustained release of the hydrophobic drug ibuprofen. In this paper, we developed a facile ring-opening polymerization (ROP) method to prepare mPEG-PTeMC copolymers under the catalysis of Novozym-435 lipase. Attractively, the polymerization has been successfully performed at 30 degrees C, close to room temperature. The data show that the copolymer compositions agree well with the feed ratio of TeMC to mPEG, indicating the controllable feature of the polymerization. The copolymer structures were characterized by (1)H NMR, IR, SEC, and DSC measurements. mPEG-PTeMC exhibits no apparent in vitro cytotoxicity toward human embryonic kidney transformed 293T cells. Those amphiphilic copolymers can readily self-assemble into nanosized micelles (about 150 nm) in aqueous solution. Their critical micelle concentrations are in the range of (1.6 9.3) x 10(-7) mol/L, determined by fluorescence spectroscopy. The micelles present high stability in PBS solution, with no obvious change in micelle diameters over 5 days. Ibuprofen can be loaded effectively in mPEG-PTeMC micelles, and its sustained release behavior is observed. Transmission electron microscopy shows that the well-dispersed spherical micelles are around 25 nm in diameter, while the diameter is 30 nm after loading ibuprofen. The release rate increases when the chain length of the PTeMC block decreases. These properties show that the micelles self-assembled from mPEG-PTeMC copolymers would have great potential as carriers for the effective encapsulation as well as sustained release of hydrophobic drugs. PMID- 20356151 TI - Electrostatic grafting of diamond nanoparticles: a versatile route to nanocrystalline diamond thin films. AB - Nanodiamond (ND) seeding is a well-established route toward the CVD (chemical vapor deposition) synthesis of diamond ultrathin films. This method is based on the deposition onto a substrate of diamond nanoparticles which act as pre existing sp(3) seeds. Here, we report on a straightforward method to disperse diamond nanoparticles on a substrate by taking advantage of the electrostatic interactions between the nanodiamonds and the substrate surface coated with a cationic polymer. This layer-by-layer deposition technique leads to reproducible and homogeneous large-scale nanoparticle deposits independent of the substrate's nature and shape. No specific functionalization of the nanoparticles is required, and low concentrated solutions can be used. The density of NDs on the substrate can be controlled, as shown by in situ ATR-FTIR (attenuated total reflection Fourier transform infrared) analysis and QCM (quartz crystal microbalance) measurements. Highly dense and compact ND deposits can be obtained, allowing CVD growth of nanocrystalline diamond ultrathin films (70 nm) on various substrates. The synthesis of 3D structured and patterned diamond thin films has also been demonstrated with this method. PMID- 20356153 TI - Fabrication of stable nanocylinder arrays in highly birefringent films of an amphiphilic liquid-crystalline diblock copolymer. AB - An amphiphilic liquid-crystalline diblock copolymer (LCDC) with a highly birefringent cyanobiphenyl (CB) group as a mesogen was prepared by atom-transfer radical polymerization. The obtained LCDC showed a well-defined structure and a narrow molecular-weight distribution. In its spin-coated films, both liquid crystalline (LC) alignment and microphase-separated nanostructures were systematically studied. Random LC arrangement and ambiguous microphase separation were observed in as-prepared films because of the high viscosity at room temperature. Upon annealing of the films in an isotropic phase of the LCDC, the CB mesogens self-organized into a smectic texture of a conic fan and the microphase separation proceeded completely. It is the supramolecular cooperative motion that enables the LCDC to hierarchically assemble into a regular patterning of normally aligned nanocylinders to the substrate, dispersed in the out-of-plane oriented mesogens. With the help of homogeneous alignment of the CB groups induced by a rubbing technique, uniform patterning of highly ordered nanocylinders parallel to the rubbing direction was successfully fabricated in the plane. The fabricated perpendicular and parallel patterning of nanocylinders dispersed in the highly birefringent films with the CB block as the majority phase show good stability under room light, indicating their potential applications as nanotemplates for preparing advanced nanoscaled materials. PMID- 20356152 TI - Centrifugal deposition of microgels for the rapid assembly of nonfouling thin films. AB - Thin films assembled from microgel building blocks have been constructed using a simple, high-throughput, and reproducible centrifugation (or "active") deposition technique. When compared to a common passive adsorption method (e.g., dip coating), microgels that are actively deposited onto a surface have smaller footprints and are more closely packed. Under both active and passive deposition conditions, the microgel footprint areas decrease during deposition. However, under active deposition, the microgel footprint appears to decrease continually and to a greater degree over the course of the deposition, forming a tightly packed, homogeneous film. Taking advantage of the rapid and uniform assembly of these films, we demonstrate the use of active deposition toward the fabrication of polyelectrolyte multilayers containing anionic microgels and a cationic linear polymer. Microgel multilayers successfully demonstrated effective blocking of the underlying substrate toward macrophage adhesion, which is a highly sought-after property for modulating the inflammatory response to an implanted biomaterial. PMID- 20356154 TI - A substrate-independent approach for bactericidal surfaces. AB - Existing methods for imparting antibacterial performance to solid surfaces tend to either be substrate-specific or rely upon leaching modes of action that cause ecological damage. An alternative approach is outlined comprising plasmachemical functionalization of solid surfaces with poly(4-vinyl pyridine) moieties and their subsequent activation (quaternization) with bromobutane to yield bactericidal activity. These bioactive surfaces can be applied to a host of different substrate materials and are easily regenerated by rinsing in water. PMID- 20356155 TI - Thermocleavable materials for polymer solar cells with high open circuit voltage a comparative study. AB - The search for polymer solar cells giving a high open circuit voltage was conducted through a comparative study of four types of bulk-heterojunction solar cells employing different photoactive layers. As electron donors the thermo cleavable polymer poly-(3-(2-methylhexyloxycarbonyl)dithiophene) (P3MHOCT) and unsubstituted polythiophene (PT) were used, the latter of which results from thermo cleaving the former at 310 degrees C. As reference, P3HT solar cells were built in parallel. As electron acceptors, either PCBM or bis-[60]PCBM were used. In excess of 300 solar cells were produced under as identical conditions as possible, varying only the material combination of the photo active layer. It was observed that on replacing PCBM with bis[60]PCBM, the open circuit voltage on average increased by 100 mV for P3MHOCT and 200 mV for PT solar cells. Open circuit voltages approaching 1 V were observed for the PT:bis[60]PCBM solar cells and a maximum conversion efficiency of 1.3% was obtained for solar cells with P3MHOCT:PCBM as the photoactive material. For the reference solar cells maximum efficiencies of 2.1 and 2.4% were achieved for P3HT:PCBM and P3HT:bis[60]PCBM, respectively. Despite special measures taken in terms of substrate design and device processing, a substantial spread in the photovoltaic properties was generally observed. This spread could not be correlated with the optical properties of the solar cells, the thickness of the photo active layer or the electrode deposition conditions of the aluminum top electrode. PMID- 20356156 TI - Self-assembly of silver-aminosilica nanocomposites through silver nanoparticle fusion on hydrophobic surfaces. AB - Silver-nanoparticle-embedded aminosilica colloids synthesized via aminosilane induced spontaneous reduction reaction exhibit selective adhesion properties on hydrophobic surfaces and have been utilized as a simple and one-step procedure to create patterned nanocomposite film with silver to aminosilica mole ratio at 0.9:1. Substrates that enable self-assembly of the colloids include silicon wafer, polydimethylsiloxane, and microscope slide, where patterns of hydrophilic surface were either created using oxygen plasma treatment or stamped with chemical ink using microcontact printing. Upon substrates being immersed in a solution containing silver-aminosilica colloids, particles attach to hydrophobic surfaces and continuously self-assemble onto the deposited film, allowing us to fabricate nanocomposite patterns with controllable thickness (approximately 200 nm). PMID- 20356157 TI - Efficient green electrophosphorescence with Al cathode using an effective electron-injecting polymer as the host. AB - Efficient green phosphorescent polymer light-emitting diodes (PLED) based on aluminum (Al) cathode were demonstrated. The device composed of neutral aminoalkyl substituted polyfluorene, poly[(9,9-bis(3'-(N,N-dimethylamino)propyl) 2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) as the host and an Ir complex, fac-tris(2-(4-tert-butyl)-phenylpyridine)iridium (Ir(Bu-PPy)(3)), as the dopant. High luminous efficiency of 35.7 cd/A and a luminance of more than 10 000 cd/m(2) were obtained. The device performance was comparable to those of the devices from (Ir(Bu-PPy)(3)), doped into PVK as the host with a low work-function metal as cathode (such as barium and calcium). We found out that the high-performance was due to the effective electron injection from PFN/Al bilayer cathode, improved charge balance as well as significant reduction of back-transfer of excitons from Ir complex to the low-lying PFN triplet level in the PVK/PFN interface. PMID- 20356158 TI - Supramolecular-templated thick mesoporous titania films for dye-sensitized solar cells: effect of morphology on performance. AB - Highly crystallized mesoporous titania films of varying thicknesses and different morphologies, namely ordered body-centered orthorhombic and disordered wormlike mesostructure, have been successfully synthesized via a supramolecular-templated route and subsequent layer-by-layer deposition. The performance of these mesoporous films in dye-sensitized solar cells was investigated, achieving a maximum efficiency of 6-7% at the film thickness of 5-6 mum. The ordered mesoporous titania films outperformed the disordered counterpart of the same thickness in both short circuit current and efficiency. This behavior is elaborated with the dye-loading, optical, and charge-transport behavior as affected by the variation in mesoporous film morphology. The improved cell performance of the ordered mesoporous film is ascribed to the enhanced electron transport in the regularly packed titania network because of the enhanced crystalline grain connectivity. Nevertheless, the dependence of cell performance on the film morphology is weakened when the film thickness was above approximately 3.5 mum, because of the serious film cracks. PMID- 20356159 TI - Aminoclay: a designer filler for the synthesis of highly ductile polymer nanocomposite film. AB - Water-dispersible aminoclay synthesized in a single step process was used as an inorganic filler for preparing polyvinyl alcohol (PVA)-clay hybrid films. The PVA clay hybrid films with different weight percentages of aminoclay were obtained by simple mixing and casting of aqueous solutions of clay and polymer. The composite films show excellent retention of ductile behavior of the polymer, PVA, even at higher loadings (20 wt %) of aminoclay. Introduction of aminoclay stabilized Ag nanoparticles significantly improved the mechanical properties of the composite film. The oxygen barrier property of the composite film was improved with the increase in composition of the clay. PMID- 20356160 TI - Grafting poly(methyl methacrylate) onto polyimide nanofibers via "click" reaction. AB - Surface modification of azide-decorated polyimide (PI) nanofibers with well defined alkyne-terminated poly(methyl methacrylate) (PMMA) was accomplished via the combination of atom transfer radical polymerization (ATRP) and "click" chemistry. In this work, PI nanofibers were prepared via electrospun polyamic acid (PAA), followed by thermal imidization. Grafting of PMMA onto PI nanofibers was accomplished in three steps: (1) choloromethylation and azidization of PI nanofibers; (2) preparation of alkyne-terminated PMMA by ATRP of methyl methacrylate in toluene using propargyl 2-bromopropionate as initiator; (3) click coupling between the azidized PI nanofibers and the alkyne-terminated PMMA under the catalysis of Cu(I)Br/N,N,N',N''-pentamethyldiethylenetriamine (PMDETA). Gel permeation chromatography (GPC), (1)H NMR, and Fourier transform infrared (FT-IR) all confirmed the structure of alkyne-terminated poly(methyl methacrylate). The modified surface was characterized by X-ray photoelectron spectroscopy (XPS) after each modification stage. XPS and scanning electron microscope (SEM) were utilized to confirm PMMA-functionalized PI nanofibers, showing polymer coatings present on the surface of PI nanofibers. PI-g-PMMA nanofibers exhibited a more significant reinforcing effect compared to that with ungrafted PI nanofibers. PMID- 20356161 TI - Phase behavior and ionic conductivity of concentrated solutions of polystyrene poly(ethylene oxide) diblock copolymers in an ionic liquid. AB - Concentrated solutions of poly(styrene-b-ethylene oxide) (PS-PEO) diblock copolymers were prepared using the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMI][TFSI] as the solvent. The self-assembled microstructures adopted by the copolymer solutions have been characterized using small-angle X-ray scattering. Lyotropic mesophase transitions were observed, with a progression from hexagonally packed cylinders of PEO, to lamellae, to hexagonally packed cylinders of PS upon increasing [EMI][TFSI] content. The change in lamellar domain spacing with ionic liquid concentration was found to be comparable to that reported for other block copolymers in strongly selective solvents. The ionic conductivity of the concentrated PS-PEO/[EMI][TFSI] solutions was measured via impedance spectroscopy, and ranged from 1 x 10(-7) to 1 x 10(-3) S/cm at temperatures from 25 - 100 degrees C. Additionally, the ionic conductivity of the solutions was found to increase with both ionic liquid concentration and molecular weight of the PEO blocks. The ionic conductivity of PEO homopolymer/[EMI][TFSI] solutions was also measured in order to compare the conductivity of the PS-PEO solutions to the expected limit for a lamellar sample with randomly oriented microstructure grains. PMID- 20356162 TI - Solvent-annealing-induced self-organization of poly(3-hexylthiophene), a high performance electrochromic material. AB - We have systematically studied the self-organization of poly(3-hexylthiophene) (P3HT), an electrochromic material, upon control of the solvent evaporation rate. We characterized these polymer films using atomic force microscopy and X-ray diffraction measurements. Well-ordered P3HT structures were developed after solvent annealing; these highly crystalline structures exhibited enhanced electrochromic contrast and reduced resistance within the film, leading to larger coloration efficiencies and faster switching times. The optical contrast (Delta%T), coloration efficiency, and switching time of the P3HT films increased from 54.2%, 182.6 cm(2) C(-1), and 5.3 s, respectively, prior to solvent annealing to 64.8%, 293.5 cm(2) C(-1), and 3.2 s, respectively, after application of the solvent-annealing conditions. PMID- 20356163 TI - Silver oxide nanowalls grown on Cu substrate as an enzymeless glucose sensor. AB - Ag(2)O nanowalls consisting of densely packed nanoplates based on a Cu substrate were synthesized through a facile one-pot hydrothermal method. A new enzymeless glucose sensor of Cu-Ag(2)O nanowalls was fabricated. The Cu-Ag(2)O nanowalls showed higher catalysis on glucose oxidation than traditional Ag(2)O nanoflowers and Cu-Ag(2)O nanospindles. At an applied potential of 0.4 V, the sensor produced an ultrahigh sensitivity to glucose (GO) of 298.2 microA mM(-1). Linear response was obtained over a concentration range from 0.2 mM to 3.2 mM with a detection limit of 0.01 mM (S/N = 3). Satisfyingly, the Cu-Ag(2)O nanowalls modified electrode was not only successfully employed to eliminate the interferences from uric acid (UA) acid ascorbic (AA) and also fructose (FO) during the catalytic oxidation of glucose. The Cu-Ag(2)O nanowalls modified electrode allows highly sensitive, excellently selective, stable, and fast amperometric sensing of glucose and thus is promising for the future development of nonenzymatic glucose sensors. PMID- 20356164 TI - Synthesis, physicochemical, and tribological characterization of S-Di-n octoxyboron-O,O'-di-n-octyldithiophosphate. AB - Dialkyldithiophosphates (DTPs) of zinc(II), copper(II), and other metals have been extensively used as multifunctional additives in lubricants to control friction and reduce wear in mechanical systems. Among these DTP compounds, zinc dialkyldithiophosphates (ZnDTPs) are the most common additives extensively used for more than 60 years. These additives form a protective film on steel surfaces and, thus, control friction and reduce wear. However, ZnDTPs contain zinc and large amounts of phosphorus and sulfur, which impair the environment, both directly and indirectly, by adversely affecting the performance of catalytic converters of various automobiles. For this reason, environmental legislation imposes limitations on concentrations of phosphorus, sulfur, and zinc in the lubricants. In this work, we report on zinc-free S-di-n-octoxyboron-O,O'-di-n octyldithiophosphate (DOB-DTP) lubricant additive with amount of phosphorus and sulfur reduced by half in a molecule as compared with ZnDTPs. DOB-DTP was synthesized by a reaction in two steps under inert nitrogen atmosphere. The final product, a viscous liquid, was characterized by the elemental analysis, FT-IR, multinuclear (1)H, (13)C, (31)P, and (11)B NMR spectroscopy and thermal analyses. Tribological performance of a mineral oil with this new additive was evaluated in comparison with O,O'-di-n-butyl-dithiophosphato-zinc(II) (ZnDTP) using a four ball tribometer. The surface morphology and the elemental composition of the tribofilms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS). The results show that DOB-DTP has a considerably better antiwear performance and higher stability of the coefficient of friction with time as compared with ZnDTP. Both phosphorus and sulfur were detected by the EDS on the worn steel surfaces at all concentrations of additives in the base oil. PMID- 20356165 TI - Large-area fabrication of patterned ZnO-nanowire arrays using light stamping lithography. AB - We demonstrate selective adsorption and alignment of ZnO nanowires on patterned poly(dimethylsiloxane) (PDMS) thin layers with (aminopropyl)siloxane self assembled monolayers (SAMs). Light stamping lithography (LSL) was used to prepare patterned PDMS thin layers as neutral passivation regions on Si substrates. (3 Aminopropyl)triethoxysilane-based SAMs were selectively formed only on regions exposing the silanol groups of the Si substrates. The patterned positively charged amino groups define and direct the selective adsorption of ZnO nanowires with negative surface charges in the protic solvent. This procedure can be adopted in automated printing machines that generate patterned ZnO-nanowire arrays on large-area substrates. To demonstrate its usefulness, the LSL method was applied to prepare ZnO-nanowire transistor arrays on 4-in. Si wafers. PMID- 20356166 TI - Polyelectrolyte multilayer-assisted immobilization of zero-valent iron nanoparticles onto polymer nanofibers for potential environmental applications. AB - We report a facile approach to synthesizing and immobilizing zero-valent iron nanoparticles (ZVI NPs) onto polyelectrolyte (PE) multilayer-assembled electrospun polymer nanofibers for potential environmental applications. In this approach, negatively charged cellulose acetate (CA) nanofibers fabricated by electrospinning were assembled with multilayers of poly(diallyldimethylammonium chloride) (PDADMAC) and polyacrylic acid (PAA) through electrostatic layer-by layer assembly. The formed PAA/PDADMAC multilayers onto CA nanofibers were then used as a nanoreactor to complex Fe(II) ions through the binding with the free carboxyl groups of PAA for subsequent reductive formation of ZVI NPs. Combined scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetry analysis studies demonstrate that the ZVI NPs are successfully synthesized and uniformly distributed into the PE multilayers assembled onto the CA nanofibers. The produced hybrid nanofibrous mats containing ZVI NPs were found to exhibit superior capability to decolorize acid fuchsin, an organic dye in dyeing wastewater. We show that the loading capacity of ZVI NPs can be tuned by changing the number of PE layers and the cycles of binding/reduction process. Increasing the number of the binding/reduction cycles leads to a slight bigger size of the ZVI NPs, which is not beneficial for improving the reactivity of ZVI NPs. The present approach to synthesizing and immobilizing ZVI NPs onto polymer nanofibers opens a new avenue to fabricating various fiber-based composite materials with a high surface area to volume ratio for environmental, catalytic, and sensing applications. PMID- 20356167 TI - Micropatterned polymer films by vapor-induced phase separation using permeable molds. AB - Microstructured polymeric films are fabricated by a novel replication method. A polymer solution is applied and contained between two substrates, of which at least one is a patterned PDMS mold. The ensemble is then put in an atmosphere containing water vapor, which diffuses through the PDMS. The absorption of water into the polymer solution causes the precipitation (phase separation) of the polymer while in contact with the microstructured molds. The thickness of the PDMS slab can be exploited to tune the water vapor transport and hence the phase separation kinetics and resulting polymer morphology. Removal of excess polymer solution from between two PDMS slabs, followed by vapor induced phase separation, can also result in microperforated polymer films with great control over the dimensions. PMID- 20356168 TI - Hierarchically structured titania films prepared by polymer/colloidal templating. AB - Hierarchically structured titania films for application in hybrid solar cells are prepared by combining microsphere templating and sol-gel chemistry with an amphiphilic diblock copolymer as a structure-directing agent. The films have a functional structure on three size scales: (1) on the micrometer scale a holelike structure for reduction of light reflection, (2) on an intermediate scale macropores for surface roughening and improved infiltration of a hole transport material, and (3) on a nanometer scale a mesoporous structure for charge generation. Poly(dimethyl siloxane)-block-methyl methacrylate poly(ethylene oxide) (PDMS-b-MA(PEO)) is used as a structure-directing agent for the preparation of the mesopore structure, and poly(methyl methacrylate) (PMMA) microspheres act as a template for the micrometer-scale structure. The structure on all levels is modified by the method of polymer extraction as well as by the addition of PMMA particles to the sol-gel solution. Calcination results in structures with increased size and a higher degree of order than extraction with acetic acid. With addition of PMMA a microstructure is created and the size of the mesopores is reduced. Already moderate microstructuring results in a strong decrease in film reflectivity; a minimum reflectivity value of less than 0.1 is obtained by acetic acid treatment and subsequent calcination. PMID- 20356169 TI - Electrochemical and structural characterization of polymer gel electrolytes based on a PEO copolymer and an imidazolium-based ionic liquid for dye-sensitized solar cells. AB - Polymer electrolytes based on mixtures of poly(ethylene oxide-co-propylene oxide) and 1-methyl-3-propyl-imidazolium iodide (MPII) were investigated, aiming at their application in dye-sensitized solar cells (DSSC). The interactions between the copolymer and the ionic liquid were analyzed by infrared spectroscopy and (1)H NMR. The results show interactions between the ether oxygen in the polymer and the hydrogen in the imidazolium cations. The ionic conductivities, electrochemical behaviors, and thermal properties of the electrolytes containing different concentrations of MPII were investigated. The electrolyte containing 70 wt % MPII presented the highest ionic conductivity (2.4 x 10(-3) S cm(-1)) and a diffusion coefficient of 1.9 x 10(-7) cm(2) s(-1). The influence of LiI addition to the electrolytes containing different concentrations of MPII was also investigated. The DSSC assembled with the electrolyte containing 70 wt % MPII showed an efficiency of 3.84% at 100 mW cm(-2). The stability of the devices for a period of 30 days was also evaluated using sealed cells. The devices assembled with the electrolyte containing less ionic liquid showed to be more stable. PMID- 20356170 TI - In situ ATR-FTIR investigation on the preparation and enantiospecificity of chiral polyelectrolyte multilayers. AB - Chiral polyelectrolyte multilayers (PEMs) consisting of poly(l-lysine) (PLL), poly(N-(S)alkylated 4-vinylpyridinium iodide), or poly(ethyleneimine maltose) (PEI-m) as polycations and poly(styrenesulfonic acid) sodium salt (PSS) or poly(vinyl sulfate) as polyanions, as well as a nonchiral PEM composed of poly(ethyleneimine) (PEI) and PSS were deposited on silicon substrates and poly(tetrafluoroethylene) membranes using the layer-by-layer method. For these PEMs, enantiospecific interaction toward one enantiomer of either l/d-glutamic acid (l/d-GLU), l/d-tryptophan, or l/d-ascorbic acid (l/d-ASC), respectively, was studied under variation of the concentration, pH, and ionic strength. Both deposition and enantiospecific interaction were analyzed by attenuated total reflection Fourier transform infrared spectroscopy. Our results show a significant enantiospecific preference of d-GLU over l-GLU at PEMs containing PLL and of d-ASC over l-ASC at PEMs containing PEI-m. No such enantiospecific preference was found for nonchiral PEMs containing PEI. The enantiospecificity of PEMs of PLL/PSS toward l/d-GLU could be significantly influenced by the ionic strength and pH values, so that increasing attractive electrostatic interactions resulted in higher enantiospecificity. PMID- 20356171 TI - Few-layer graphene as a support film for transmission electron microscopy imaging of nanoparticles. AB - One consistent limitation for high-resolution imaging of small nanoparticles is the high background signal from the amorphous carbon support film. With interest growing for smaller and smaller nanostructures, state of the art electron microscopes are becoming necessary for rudimentary tasks, such as nanoparticle sizing. As a monolayer of carbon, free-standing graphene represents the ultimate support film for nanoparticle imaging. In this work, conventional high-resolution transmission electron microscopy (HRTEM) and aberration-corrected scanning transmission electron microscopy (STEM) were used to assess the benefits and feasibility of few-layer graphene support films. Suspensions of few-layer graphene to produce the support films were prepared by simple sonication of exfoliated graphite. The greatest benefit was observed for conventional HRTEM, where lattice resolved imaging of sub 2 nm CdSe nanocrystals was achieved. The few-layer graphene films were also used as a support film for C(s)-corrected STEM and electron energy loss spectroscopy of CuInSe(2) nanocrystals. PMID- 20356172 TI - Pore size and volume effects on the incorporation of polymer into macro- and mesoporous zirconium titanium oxide membranes. AB - Macro- and mesoporous hybrid materials have applications in the fields of drug delivery, catalysis, biosensing, and separations. The pore size requirements must be well-understood to maximize the performance (e.g., load capacity and accessibility) of such materials. Hybrid materials were prepared by coating five distinct macroporous commercial membranes with zirconium titanium oxide through sol-gel chemistry. Calcination of these templated materials produced oxide membranes which had a suite of macropore and mesopore architectures, pore volumes, and surface areas. These differences in physical properties were used to conduct a fundamental study on the relationship between the pore size and volume and the polymer incorporation. Metal oxide membranes were postsynthetically modified with poly(ethyleneimine) (PEI) ranging in molecular weight from 1300 to 1 000 000 Da (1.2-11 nm in hydrodynamic diameter). The incorporation of the polymer from a 9 wt % solution at pH 10 was highly dependent on the pore size and pore volume. As the surface area increased, loading capacity decreased, indicating that much of the increased internal surface, due to small pore diameters (< or = 8 nm), was inaccessible to the macromolecules. Exclusion of PEI from small mesopores was apparent even for the lowest molecular weight polymer. A high maximum loading of 1.25 mg m(-2) of 600 000-1 000 000 Da PEI was achieved in the metal oxide with the largest minimum mesopore diameter. Thus, mesopore diameter and pore volume must be considered when designing a mesoporous solid support. PMID- 20356173 TI - Surface functionalization of a poly(vinylidene fluoride): effect on the adhesive and piezoelectric properties. AB - We studied the effect of the surface functionalization and crystalline phase change of poly(vinylidene fluoride) (PVDF) films on their adhesion and piezoelectric properties. The surface modification of PVDF was carried out with ion beam and/or plasma treatment. These surface modifications were found to alter the interfacial strength between PVDF and metal electrodes and the crystal structure of the piezoelectric PVDF film. A remarkable improvement was found in the interfacial adhesion of the films with thermally deposited metal electrodes, but some piezoelectricity of PVDF film was lost due to the changes in the crystal phase. The proper treatment condition for enhancing the adhesion and retaining piezoelectric structure was suggested. PMID- 20356174 TI - Nanostructured silver-based surfaces: new emergent methodologies for an easy detection of analytes. AB - In this work, we describe how to realize a new sensing platform for an easy and fast detection of analytes. In particular, we utilized enhanced fluorescence emission on silver island films (SIFs) coupled to the total internal reflection fluorescence mode (TIRF) to develop a new assay format for the detection of target analytes. Here, as an example, we report on the detection of the toxic peptides present in gliadin (Gli). Our assay was performed as follows: (1) gliadin was first captured on surfaces coated with anti-Gli antibodies; (2) the surfaces were then incubated with fluorophore-labeled anti-Gli antibodies; (3) the signal from the fluorophore-labeled anti-Gli antibody bound to the antigen was detected by TIRF. The system was examined on glass surfaces and on SIFs. We observed a relevant enhancement of the signal from SIFs compared to the signal from the glass substrate not modified with a SIF. In addition, the estimated detection limit (EDL) of our methodology was 60 ng/mL (or lower). This limit is therefore lower than the clinical cut-off for Gli presence in food for celiac patients. The advantage of our method is a reduced number of testing steps, which allows for easy detection of residual toxic peptides in food labeled as gluten free. The proposed technology can be easily expanded to the determination of different target analytes. PMID- 20356175 TI - Stacked silicon nanowires with improved field enhancement factor. AB - This work describes newly structured stacked silicon nanowires (s-SiNWs), consisting of nanosized silicon wires on top of silicon microrods (SiMRs) and exhibiting pronouncedly superior electron field emission (EFE) characteristics to the conventional SiNWs, by using a two-step electroless metal deposition process. Experimental results indicate that for these s-SiNWs, the electrostatic "screen effect" is markedly suppressed and the field enhancement factor (beta-value) is significantly increased ((beta)(s-SiNWs) = 2533). Additionally, the turn-on field (E(0)) for triggering the EFE process is reduced to a level comparable with that of carbon nanotubes, viz. (E(0))(s-SiNWs) = 2.0 V/mum. This simple and robust modified electroless metal deposition approach does not require either a high temperature or an expensive photolithographic process and possesses great potential for applications. PMID- 20356176 TI - Ultrathin W-Al dual interlayer approach to depositing smooth and adherent nanocrystalline diamond films on stainless steel. AB - The adherence of diamond coated on steel is commonly low and needs to be strengthened with thick intermediate layers. In this paper, a nanoscale W-Al dual metal interlayer has been applied on SS304 substrates to facilitate deposition of continuous, adherent and smooth diamond thin films. During the microwave plasma enhanced chemical vapor deposition process, the Al inner layer 30 nm thick diffuses into steel surface inhibiting carbon diffusion and graphitization. The W outer layer 20 nm thick is transformed into W carbides, both preventing carbon diffusion and enhancing diamond nucleation. The diamond films synthesized are of high purity and have smooth surfaces and dense structures. Indentation and shear deformation tests indicate high delaminating tolerance of the diamond films. PMID- 20356177 TI - Colorimetric detection of mercury(II) ion using unmodified silver nanoparticles and mercury-specific oligonucleotides. AB - A sensitive and selective colorimetric detection method for mercury(II) has been well-established in this paper. It was based on the conformation change of mercury-specific oligonucleotides (MSO) from random coil structure to hairpin structure upon the addition of Hg(2+) and the phenomenon of salt-induced unmodified silver nanoparticles (AgNPs) aggregation. The calibration curve showed that the net absorption ratio value at 395 and 570 nm increased linearly over the Hg(2+) concentration range of 25-500 nM with a limit of detection of 17 nM. The other environmentally relevant metal ions did not interfere with the determination of Hg(2+). PMID- 20356178 TI - Optimization of electroactive hydrogel actuators. AB - To improve actuation of hydrogels, we utilized an emulsion polymerization to engineer porous structures into polyelectrolyte hydrogels. Porous hydrogels generated large deformation as a result of enhanced deswelling mechanisms; for instance, the decreased number of COO(-) groups that must be protonated in porous hydrogels to initiate bending. Measurements of the mechanical properties revealed that porous hydrogels also bend to a larger extent because of their increased flexibility. Overall, our results demonstrate that the fast and large actuation of polyelectrolyte hydrogels can be accomplished by increasing the hydrogel porosity. PMID- 20356179 TI - In situ reaction mechanism studies on ozone-based atomic layer deposition of Al(2)O(3) and HfO(2). AB - The mechanisms of technologically important atomic layer deposition (ALD) processes, trimethylaluminium (TMA)/ozone and tetrakis(ethylmethylamino)hafnium (TEMAH)/ozone, for the growth of Al(2)O(3) and HfO(2) thin films are studied in situ by a quadrupole mass spectrometer coupled with a 300 mm ALD reactor. In addition to released CH(4) and CO(2), water was detected as one of the reaction byproduct in the TMA/O(3) process. In the TEMAH/O(3) process, the surface after the ozone pulse consisted of chemisorpted active oxygen and -OH groups, leading to the release of H(2)O, CO(2), and HNEtMe during the metal precursor pulse. PMID- 20356180 TI - The influence of charge trapping on the electrochromic performance of poly(3,4 alkylenedioxythiophene) derivatives. AB - This paper describes the electrochromic properties of a series of poly(3,4 alkylenedioxythiophene) (PXDOT) derivatives featuring various ring sizes and substitutions. The presence of a bulky group on the monomer resulted in a polymer possessing a more-open morphology, which promoted reversible ionic transfer. We used an electrochemical quartz crystal microbalance and cyclic voltammetry to investigate the properties of these polymers. We found that both cations and anions were involved in the charge compensation process. Furthermore, PXDOT derivatives possessing larger ring sizes and/or longer alkyl substituents exhibited less trapping of ions within the polymer during the redox process. The long-term electrochromic stability of these PXDOTs depended strongly on the number of trapped ions. Although the transmittance attenuation of poly(3,4 ethylenedioxythiophene) (PEDOT) decreased from 53 to 42%, we observed no significant decay for poly(diethyl-3,4-dihydro-2H-thieno[3,4-b]-[1,4]dioxepine) (PProDOT-Et(2)) after 400 cycles. PMID- 20356181 TI - Amylase-functionalized mesoporous silica thin films as robust biocatalyst platforms. AB - A robust biocatalyst was produced by immobilization of alpha-amylase into mesoporous silica thin films with local order pore structure and 11 nm pore diameter, supported on glass stripes. The activity of this novel catalyst was evaluated for direct starch degradation. The catalyst films show excellent activity, and enhanced stability with respect to free enzyme at extreme conditions of pH and temperature. In addition, they can be easily separated from the reaction media and reused several times. PMID- 20356182 TI - On the micro-, meso-, and macroporous structures of polymer electrolyte membrane fuel cell catalyst layers. AB - In this work, N(2) adsorption was employed to investigate the effects of carbon support, platinum, and ionomer loading on the microstructure of polymer electrolyte membrane fuel cell catalyst layers (CLs). Brunauer-Emmett-Teller and t-plot analyses of adsorption isotherms and pore-size distributions were used to study the microstructure of carbon supports, platinum/carbon catalyst powders, and three-component platinum/carbon/ionomer CLs. Two types of carbon supports were chosen for the investigation: Ketjen Black and Vulcan XC-72. CLs with a range of Nafion ionomer loadings were studied in order to evaluate the effect of an ionomer on the CL microstructure. Regions of adsorption were differentiated into micropores associated with the carbon primary particles (<2 nm), mesopores ascribed to the void space inside agglomerates (2-20 nm), and meso- to macroporous space inside aggregates of agglomerates (>50 nm). Ketjen Black was found to possess a significant fraction of micropores, 25% of the total pore volume, in contrast to Vulcan XC-72, for which the corresponding fraction of micropores was 15% of the total pore volume. The microstructure of the carbon support was found to be a significant factor in the formation of the microstructure in the three-component CLs, serving as a rigid porous framework for distribution of platinum and the ionomer. It was found that platinum particle deposition on Ketjen Black occurs in, or at the mouth of, the support's micropores, thus affecting its effective microporosity, whereas platinum deposition on Vulcan XC-72 did not significantly affect the support's microstructure. The codeposition of ionomer in the CL strongly influenced its porosity, covering pores < 20 nm, which are ascribed to the pores within the primary carbon particles (pore sizes < 2 nm) and to the pores within agglomerates of the particles (pore sizes of 2-20 nm). PMID- 20356183 TI - Tailor-made development of fast Li ion conducting garnet-like solid electrolytes. AB - This paper reports a novel approach to designing advanced solid Li ion electrolytes for application in various solid state ionic devices, including Li ion secondary batteries, gas sensors, and electrochromic displays. The employed methodology involves a solid-solution reaction between the two best-known fast Li ion conductors in the garnet-family of compounds Li(6)BaLa(2)M(2)O(12) (M = Nb, Ta) and Li(7)La(3)Zr(2)O(12). Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), AC impedance, and (7)Li nuclear magnetic resonance (Li NMR) spectroscopy were employed to characterize phase formation, morphology, ionic conductivity, and Li ion coordination in Li(6.5)La(2.5)BaZrMO(12). PXRD shows for formation of a cubic garnet-like structure and AC impedance data is consistent with other known solid Li ion electrolytes. Li(6.5)La(2.5)BaZrTaO(12) exhibits a fast Li ion conductivity of about 6 x 10(-3) S cm(-1) at 100 degrees C, which is comparable to that of currently employed organic polymer electrolytes value at room temperature. The Nb analogue shows an order of magnitude lower ionic conductivity than that of the corresponding Ta member, which is consistent with the trend in garnet-type electrolytes reported in the literature. Samples sintered at 1100 degrees C shows the highest electrical conductivity compared to that of 900 degrees C. (7)Li MAS NMR shows a sharp single peak at 0 ppm with respect to LiCl, which may be attributed to fast migration of ions between various sites in the garnets, and also suggesting average distributions of Li ions at average octahedral coordination in Li(6.5)La(2.5)BaZrMO(12). The present work together with literature used to establish very important fundamental relationship of functional property-Li concentration-crystal structure-Li diffusion coefficient in the garnet family of Li ion electrolytes. PMID- 20356184 TI - Dependence of pentacene crystal growth on dielectric roughness for fabrication of flexible field-effect transistors. AB - The dependence of pentacene nanostructures on gate dielectric surfaces were investigated for flexible organic field-effect transistor (OFET) applications. Two bilayer types of polymer/aluminum oxide (Al(2)O(3)) gate dielectrics were fabricated on commercial Al foils laminated onto a polymer back plate. Some Al foils were directly used as gate electrodes, and others were smoothly polished by an electrolytic etching. These Al surfaces were then anodized and coated with poly(alpha-methyl styrene) (PAMS). For PAMS/Al(2)O(3) dielectrics onto etched Al foils, surface roughness up to approximately 1 nm could be reached, although isolated dimples with a lateral diameter of several micrometers were still present. On PAMS/Al(2)O(3) dielectrics (surface roughness >40 nm) containing mechanical grooves of Al foil, average hole mobility (mu(FET)) of 50 nm thick pentacene-FETs under the low operating voltages (|V| < 6 V) was approximately 0.15 cm(2) V(-1) s(-1). In contrast, pentacene-FETs employing the etched Al gates exhibited mu(FET) of approximately 0.39 cm(2) V(-1) s(-1), which was comparable to that of reference samples with PAMS/Al(2)O(3) dielectrics onto flat sputtered Al gates. Conducting-probe atomic force microscopy and two-dimensional X-ray diffraction of pentacene films with various thicknesses revealed different out-of plane and in-plane crystal orderings of pentacene, depending on the surface roughness of the gate dielectrics. PMID- 20356185 TI - Composites of plasma surface functionalized barium titanate nanoparticles covalently attached to epoxide matrices: synthesis and evaluation. AB - Inorganic/organic nanocomposites consisting of surface functionalized barium titanate (BTO) nanoparticles covalently bonded to epoxy polymeric matrices are described. A plasma-enhanced CVD process was employed to functionalize the particle surfaces with reactive amine groups. Subsequently, these modified particles were reacted with an epoxide monomer to synthesize the final nanocomposites, containing particle loadings ranging from 1 to 5 weight percent. Control samples, containing unmodified BTO, were also synthesized under identical reaction conditions and particle loading. The resultant nanocomposites were characterized spectroscopically and microscopically, and their physical and thermal properties were evaluated. The results obtained reveal a more uniform distribution of the surface modified BTO in the composites relative to that observed with the unmodified particles. Additionally, the physical and thermal properties of the nanocomposites containing the plasma modified particles were determined to be significantly improved over that of the pure polymer or the composites containing the unmodified particles, for each level of loading employed in this study. In light of these improved properties, it appears that the surface modifications employed significantly improve the interfacial interactions between the inorganic particles and the organic matrices in these nanocomposites. PMID- 20356186 TI - Photoluminescence and photoconductivity of ZnS-coated ZnO nanowires. AB - ZnO nanowires (NWs) with a ZnS coating are synthesized in order to modify the surface without changing the diameter of the NWs. They have the wurtzite ZnO at the core and a cubic ZnS at the outer layer. The NWs show a sharp ultraviolet and a broad visible emission of the photoluminescence spectra. Surface modification has led to a change in the position of the maxima of the visible emission in ZnO ZnS NWs. The photocarrier relaxation under steady UV illumination occurs in ZnO NW arrays but is absent in ZnO-ZnS NW arrays. The dark current value for both type of NWs are similar, whereas the photocurrent value is much higher in the surface-modified NWs. Higher photocurrent value indicates a transport of the photogenerated carriers from the ZnS layer to ZnO during UV illumination. The carrier transport mechanism is proposed through a model. PMID- 20356187 TI - Polycarbazole nanocomposites with conducting metal oxides for transparent electrode applications. AB - The preparation and characterization of conducting polycarbazole (PCz) hybrid films with a colorless transparency are described. They were prepared by the vacuum evaporation of tin, aluminum, or gallium onto anion-doped green-colored PCz films, or by applying gallium to the films, followed by their exposure to ambient air. The resultant hybrid films consisting of an undoped PCz backbone and metal compounds exhibited good transparencies (90-95% at a wavelength of 550 nm). The hybrid films have a specific cross-sectional structure in which the small regions of the metal compounds are dispersed in the PCz backbone. The hybridization reaction was mechanistically explained on the basis of the combination of a metal corrosion reaction and polymer dedoping reaction, which was successfully supported by the chemical analyses of the hybrid films. The electric conductivities of the hybrid films, measured by a four-point-probe method, ranged from 2.2 x 10(-4) to 6.0 x 10(-3) S cm(-1), which are considered to be the lowest limit because the use of the hybrid films as an electrochemical electrode reveals that a network of conductive paths is preferentially formed in the film thickness direction rather than in the in-plane direction. PMID- 20356188 TI - Interactions of hydrophobically modified polyvinylamines: adsorption behavior at charged surfaces and the formation of polyelectrolyte multilayers with polyacrylic acid. AB - The structure and adsorption behaviors of two types of hydrophobically modified polyvinylamines (PVAm) containing substituents of hexyl and octyl chains were compared to a native polyvinylamine sample. The conformation of dissolved polyvinylamines was studied in aqueous salt solutions using dynamic light scattering. Modified PVAm showed hydrodynamic diameters similar to native PVAm, which indicated that all PVAm polymers were present as single molecules in solution. The adsorption of the polyvinylamines, both native and hydrophobically modified, from aqueous solution onto negatively charged silica surfaces was studied in situ by reflectometry and quartz crystal microgravimetry with dissipation. Polyelectrolyte multilayers (PEM) with up to nine individual layers were formed together with poly(acrylic acid). Obtained PEM structures were rigid and showed high adsorbed amounts combined with low dissipation, with similar results for both the modified and unmodified PVAm. This suggests that electrostatics dominated the PEM formation. At lower salt concentrations, the hydrophobically modified PVAm produced multilayers with low water contents, indicating that secondary interactions induced by the hydrophobic constituents can also have a significant influence on the properties of the formed layers. The surface structure of PEMs with nine individual layers was imaged in dry state using atomic force microscopy in a dynamic mode. Modified PVAm was found to induce a different structure of the PEM at 100 mM, with larger aggregates compared to those of native PVAm. From these results, it is proposed that modified PVAm can induce aggregation within the PEM, whereas PVAm remains as single molecules in solution. PMID- 20356189 TI - Dispersion polymerization of methyl acrylate in nonpolar solvent stabilized by block copolymers formed in situ via the RAFT process. AB - The free-radical dispersion polymerization of methyl acrylate (MA) in isododecane was carried out in the presence of a poly(2-ethylhexyl acrylate) macromolecular RAFT (reversible addition-fragmentation chain transfer) agent bearing a trithiocarbonate reactive group in the middle of the chain (P2EHA-TTC). The presence of the trithiocarbonate function was crucial for the synthesis of monodisperse colloidal poly(methyl acrylate) (PMA) particles stabilized by the P2EHA segments. The hydrodynamic diameters ranged from 100 to 300 nm, using particularly low amounts of the macro(RAFT agent) (1-6 wt % vs. MA) in dispersion polymerizations carried out at 20 wt % solids content. As shown by 2D liquid chromatography, P2EHA-b-PMA or P2EHA-b-PMA-b-P2EHA block copolymers formed in situ at the early stage of the dispersion polymerization due to the reversible transfer process and played the role of particle stabilizer. The glass-transition temperature of the derived polymer films was not affected by the low amount of the chosen macromolecular stabilizer and the mechanical properties were mainly those of PMA, which makes the technique very attractive for coating applications. PMID- 20356190 TI - Waterborne, semicrystalline, pressure-sensitive adhesives with temperature responsiveness and optimum properties. AB - The synthesis and resulting temperature-responsive properties of semicrystalline waterborne pressure-sensitive adhesives (PSAs) were investigated. A crystalline polymer fraction was produced in situ within waterborne particles by miniemulsion polymerization of non-branched long chain acrylates. The degree of crystallinity was controlled by copolymerization with a short chain acrylate. The polymerization strategy determined the polymer architecture and film structure, which then influenced the adhesion properties. The high sensitivity of the adhesion strength of these PSAs to temperature, in the range around the crystal melting point, opens up the possibility of designing temperature-responsive adhesives. With the right distribution and concentration of crystalline polymers, a simultaneous increase in both the peel strength and the shear resistance was obtained, which is a combination that is often not found when optimizing adhesive properties. PMID- 20356191 TI - Parallel effects of cations on PNIPAM graft wettability and PNIPAM solubility. AB - Stimuli-responsive surfaces grafted with thermoresponsive polymers switch from hydrophilic to hydrophobic thermally, making these surfaces attractive in applications such as in microfluidics devices, as antifouling surfaces, and in cell culture and tissue engineering. These materials exhibit changes in wettability as the polymer undergoes a phase transition above its lower critical solution temperature (LCST). Because the presence of salts affects LCSTs in accordance to the Hofmeister series, salt effects on the wettability of these thermoresponsive surfaces will dramatically impact device performance. Prior studies of such effects have focused on the influence of anions. Detailed studies of the effects of cations have not been carried out. Here, the influence of varying cation identity in a series of mono-, di-, and trivalent sulfate salts on the wettability of a stimuli-responsive grafted surface was investigated by measuring advancing water contact angle (Theta(a)) changes. The cation-induced changes in Theta(a) were correlated with corresponding changes in surface morphology examined by AFM. The results showed that the effects of varying cations on surface wettability are as large as the effects of varying anion identity and concentration (i.e., Theta(a) changes of up to 90 degrees). Parallel studies of the effects of varying the cation identity and concentration for these same cation sulfate salts in solution show that cation variation also has a large effect on the LCST of PNIPAM, the stimuli responsive polymer component of the nanocomposite grafts that were studied. Moreover, analyses of the Theta(a) and LCST data using activity showed that the Theta(a) or LCST versus cation activity/concentration could be readily grouped by charge. Such differences are not seen in similar studies where anion identity, charge, and concentration are changed. PMID- 20356192 TI - High-definition polymeric membranes: construction of 3D lithographed channel arrays through control of natural building blocks dynamics. AB - The fabrication of well-defined interfaces is in high demand in many fields of biotechnologies. Here, high-definition membrane-like arrays are developed through the self-assembly of water droplets, which work as natural building blocks for the construction of ordered channels. Solution viscosity together with the dynamics of the water droplets can decide the final formation of three dimensional well-ordered patterns resembling anodic structures, especially because solvents denser than water are used. Particularly, the polymer solution viscosity is demonstrated to be a powerful tool for control of the mobility of submerged droplets during the microfabrication process. The polymeric patterns are structured at very high levels of organization and exhibit well-established transport-surface property relationships, considered basics for any types of advanced biotechnologies. PMID- 20356193 TI - Macroscopic electrical properties of ordered single-walled carbon nanotube networks. AB - Creation of large-scale arrays of single-walled carbon nanotubes (SWNTs) with defined orientation and density is of central importance for obtaining functional electronic device structures that incorporate these nanoscaled systems. This manuscript describes how the macroscopic electrical properties of 2D SWNT networks vary controllably with the microscopic alignment individual SWNTs in the network. These studies indicate that "orthogonal" SWNT structures provide enhanced reproducibility and conductivity, when compared to deposits of highly aligned SWNTs. Because this material is composed of a submonolayer coverage of SWNTs, such deposits have applications in flexible and transparent electronic materials. PMID- 20356194 TI - Significant conductivity enhancement of conductive poly(3,4 ethylenedioxythiophene): poly(styrenesulfonate) films through a treatment with organic carboxylic acids and inorganic acids. AB - Significant conductivity enhancement was observed on transparent and conductive poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films after a treatment with organic and inorganic acids, including acetic acid, propionic acid, butyric acid, oxalic acid, sulfurous acid, and hydrochloric acid. The conductivity could be enhanced from 0.2 to over 200 S cm(-1), that is, by a factor of more than 1000. The conductivity enhancement was dependent on the structure of the acids and the experimental conditions during the treatment, such as the acid concentration and the temperature. The optimal temperature was in the range of 120 to 160 degrees C. The resistance dropped rapidly when a PEDOT:PSS film was treated with acid solution of high concentration, whereas it gradually increased and then decreased when it was treated with an acid solution of low concentration. The mechanism for this conductivity enhancement was studied by various chemical and physical characterizations. The temperature dependence of conductivity indicates that the energy barrier for charge hopping among the PEDOT chains become lower in the highly conductive PEDOT:PSS film after the acid treatment. The ultraviolet-visible-near-infrared (UV-vis-NIR) absorption spectroscopy, the X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) indicate the loss of polystyrene sulfonic acid (PSSH) chains from the PEDOT:PSS film after the acid treatment, and the atomic force microscopy (AFM) suggest conformational change of the polymer chains. Therefore, the conductivity enhancement is attributed to the loss of PSSH chains from the PEDOT:PSS film and the conformational change of the PEDOT chains, which are induced by the acids. PMID- 20356195 TI - Bicolor electroluminescent pixels from single active molecular material. AB - We report on the fabrication of the first bicolor micropixelated OLED from a single molecular material using a single-step bottom up procedure. The implementation of a deposition technique, based on a spatial-switch and conformational-sensitive STD surface-tension-driven lithography, has allowed us to exploit the spontaneous supramolecular properties and the conformational flexibility of a conjugated thiophene-based material, 6-bis-(50-hexyl-[2, 20]bithiophen-5-yl)-3, 5-dimethyl-dithieno[3, 2-b; 20, 30-d]thiophene (DTT7Me). The existence of two regularly alternating emitting regions on a micrometer scale allows obtaining electroluminescent emission at two different wavelengths from a single material. PMID- 20356196 TI - In situ synthesis of DNA microarray on functionalized cyclic olefin copolymer substrate. AB - Thermoplastic materials such as cyclic-olefin copolymers (COC) provide a versatile and cost-effective alternative to the traditional glass or silicon substrate for rapid prototyping and industrial scale fabrication of microdevices. To extend the utility of COC as an effective microarray substrate, we developed a new method that enabled for the first time in situ synthesis of DNA oligonucleotide microarrays on the COC substrate. To achieve high-quality DNA synthesis, a SiO(2) thin film array was prepatterned on the inert and hydrophobic COC surface using RF sputtering technique. The subsequent in situ DNA synthesis was confined to the surface of the prepatterned hydrophilic SiO(2) thin film features by precision delivery of the phosphoramidite chemistry using an inkjet DNA synthesizer. The in situ SiO(2)-COC DNA microarray demonstrated superior quality and stability in hybridization assays and thermal cycling reactions. Furthermore, we demonstrate that pools of high-quality mixed-oligos could be cleaved off the SiO(2)-COC microarrays and used directly for construction of DNA origami nanostructures. It is believed that this method will not only enable synthesis of high-quality and low-cost COC DNA microarrays but also provide a basis for further development of integrated microfluidics microarrays for a broad range of bioanalytical and biofabrication applications. PMID- 20356197 TI - Transparent, well-aligned TiO(2) nanotube arrays with controllable dimensions on glass substrates for photocatalytic applications. AB - Transparent, well-aligned TiO(2) nanotube arrays (NTAs) with controllable dimensions are grown on glass substrates via atomic layer deposition (ALD) of TiO(2) onto free-standing porous anodic alumina (PAA) templates. Photodegradation of aqueous methylene blue (MB) solution and solid stearic acid (SA) film using TiO(2) NTAs of various wall thicknesses are investigated. The Pd functionalized TiO(2) NTAs, with a wall thickness of 15 nm and height of 200 nm, has the highest photodegradation efficiency at 76% after 4 h of UV irradiation. These functionalized NTAs are able to photodegrade MB molecules completely as no obvious demethylated byproducts are observed during the process. It also demonstrates excellent photocatalytic activity for solid contaminants such as SA film. By using the ALD technique, the nanotube wall thickness can be precisely controlled so that it is sufficiently thin to be transparent while sufficiently thick for excellent photocatalytic performances. The transparent TiO(2) NTAs on glass substrates with excellent photocatalytic properties might have potential applications in self-cleaning coating, transparent electronics, and solar cells. PMID- 20356198 TI - Effect of solvent and subsequent thermal annealing on the performance of phenylenevinylene copolymer: PCBM solar cells. AB - The morphology of the photoactive layer used in the bulk heterojunction photovoltaic devices is crucial for efficient charge generation and their collection at the electrodes. We investigated the solvent vapor annealing and thermal annealing effect of an alternating phenylenevinylene copolymer P:PCBM blend on its morphology and optical properties. The UV-visible absorption spectroscopy shows that both solvent and thermal annealing can result in self assembling of copolymer P to form an ordered structure, leading to enhanced absorption in the red region and hole transport enhancement. By combining the solvent and thermal annealing of the devices, the power conversion efficiency is improved. This feature was attributed to the fact that the PCBM molecules begin to diffuse into aggregates and together with the ordered copolymer P phase form bicontinuous pathways in the entire layer for efficient charge separation and transport. Furthermore, the measured photocurrent also suggests that the space charges no longer limit the values of the short circuit current (J(sc)) and fill factor (FF) for solvent-treated and thermally annealed devices. These results indicate that the higher J(sc) and PCE for the solvent-treated and thermally annealed devices can be attributed to the phase separation of active layers, which leads to a balanced carrier mobility. The overall PCE of the device based on the combination of solvent annealing and thermal annealing is about 3.7 %. PMID- 20356199 TI - Dielectric surface-controlled low-voltage organic transistors via n-alkyl phosphonic acid self-assembled monolayers on high-k metal oxide. AB - In this paper, we report on n-alkyl phosphonic acid (PA) self-assembled monolayer (SAM)/hafnium oxide (HfO(2)) hybrid dielectrics utilizing the advantages of SAMs for control over the dielectric/semiconductor interface with those of high-k metal oxides for low-voltage organic thin film transistors (OTFTs). By systematically varying the number of carbon atoms of the n-alkyl PA SAM from six to eighteen on HfO(2) with stable and low leakage current density, we observe how the structural nature of the SAM affects the thin-film crystal structure and morphology, and subsequent device performance of low-voltage pentacene based OTFTs. We find that two primary structural factors of the SAM play a critical role in optimizing the device electrical characteristics, namely, the order/disorder of the SAM and its physical thickness. High saturation-field effect mobilities result at a balance between disordered SAMs to promote large pentacene grains and thick SAMs to aid in physically buffering the charge carriers in pentacene from the adverse effects of the underlying high-k oxide. Employing the appropriate n-alkyl PA SAM/HfO(2) hybrid dielectrics, pentacene based OTFTs operate under -2.0 V with low hysteresis, on-off current ratios above 1 x 10(6), threshold voltages below -0.6 V, subthreshold slopes as low as 100 mV dec(-1), and field-effect mobilities as high as 1.8 cm(2) V(-1) s(-1). PMID- 20356200 TI - Direct fabrication of highly nanoporous polystyrene fibers via electrospinning. AB - A direct approach for fabricating nanoporous polymer fibers via electrospinning has been demonstrated. Polystyrene (PS) fibers with micro- and nanoporous structures both in the core and/or on the fiber surfaces were electrospun in a single process by varying solvent compositions and solution concentrations of the PS solutions. The porous structures of the fibrous mats were characterized by field emission scanning electron microscopy and Brunauer-Emmett-Teller measurements to confirm that they could be accurately controlled by tuning vapor pressure of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF) solvent mixtures and PS concentrations in the solutions. As the solution concentration decreased, the average fiber diameter decreased, whereas the bead density increased dramatically to show a beads-on-string morphology. Both the specific surface area and pore volume of the fibrous mats showed a unimodal distributions centered at 1/3 THF /DMF mix ratio. Fibers formed from 5 wt % PS in the 1/3 THF and DMF mixtures had the largest specific surface area of 54.92 m(2) g(-1) and a pore volume of 0.318 cm(3)g(-1), respectively. PMID- 20356201 TI - Polyelectrolyte-bridged metal/cotton hierarchical structures for highly durable conductive yarns. AB - A novel, facile, and versatile approach for preparing highly durable, electrically conductive cotton yarns is reported. Polyelectrolyte brushes, a polymer that covalently tethers one end on a surface, are first grown from cotton surfaces by surface-initiated atomic transfer radical polymerization. Subsequent electroless deposition of metal particles onto the brush-modified cotton yarns yields electrically conductive yarns, which have conductivity as high as approximately 1 S/cm and can be used as electrical wires in wearable, flexible electronic devices. Importantly, the formation of polymer brush-bridged metal/cotton hierarchical structures provides robust mechanical and electrical durability to the yarns under many stretching, bending, rubbing, and washing cycles. With proper selection of metal, the conductivity of the samples remains stable after they are stored in air for a few months. This chemical approach can be extended as a general method for making conductive yarns and fabrics from all kinds of natural fibers. PMID- 20356202 TI - Thin films of conductive ZnO patterned by micromolding resulting in nearly isolated features. AB - Patterned and continuous thin films of conductive Al-doped zinc oxide (ZnO:Al) were prepared on different substrates from a polymeric precursor solution. Their electric conductivity and light transmittance (for visible and UV light) was measured at room temperature. By means of a simple device, conductive ZnO:Al films with high fidelity patterns with features of 2-20 microm width could be obtained by simply micromolding the liquid precursor film prior to heat treatment. The individual features were interconnected by a very thin residual ZnO layer. PMID- 20356203 TI - Montmorillonite-supported Ag/TiO(2) nanoparticles: an efficient visible-light bacteria photodegradation material. AB - Montmorillonite (MMT)-supported Ag/TiO(2) composite (Ag/TiO(2)/MMT) has been prepared through a one-step, low-temperature solvothermal technique. Powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) reveal that the Ag particles coated with TiO(2) nanoparticles are well-dispersed on the surface of MMT in the composite. As a support for the Ag/TiO(2) composite, the MMT prevents the loss of the catalyst during recycling test. This Ag/TiO(2)/MMT composite exhibits high photocatalytic activity and good recycling performance in the degradation of E. coli under visible light. The high visible-light photocatalytic activity of the Ag/TiO(2)/MMT composite is ascribed to the increase in surface active centers and the localized surface plasmon effect of the Ag nanoparticles. The Ag/TiO(2)/MMT materials with excellent stability, recyclability, and bactericidal activities are promising photocatalysts for application in decontamination. PMID- 20356204 TI - Subambient temperature CO(2) and light gas permeation through segmented block copolymers with tailored soft phase. AB - The permeation properties of a series of block copolymers based on poly(ethylene oxide)-ran-poly(propylene oxide) (PEO-ran-PPO) soft segments and monodisperse tetra-amide (T6T6T) hard segments have been studied. The polyether soft segment used in the current study differs from the commonly used pure poly(ethylene oxide) (PEO) soft segment by the fact that it contains 25 wt % randomly distributed poly(propylene oxide) (PPO). The presence of the methyl group of PPO suppresses crystallization of the soft segment and strongly improves the permeability of these materials, especially at subambient temperatures. In addition, the unique monodisperse character of the hard segment ensures a very well phase-separated morphology, resulting in a very pure soft phase. The soft segment length of these block copolymers was varied between 1000 and 10000 g/mol (62-89 wt %). High soft segment concentrations and flexibility were obtained resulting in high CO(2) permeabilities (up to 570 Barrer at 50 degrees C). Due to the random distribution of PPO in the predominantly PEO based soft segment crystallization of PEO was not observed at temperatures as low as -10 degrees C. CO(2) permeabilities exceeding 200 Barrer could be obtained at this low temperature. The CO(2)/light gas selectivity in these materials is governed by the solubility selectivity and consequently only slightly lowered because of the introduction of PPO in the soft segment. Comparison with literature revealed that this block copolymer system has exceptionally high CO(2) permeabilities combined with reasonable CO(2)/light gas selectivities. It is very interesting in CO(2) separation processes where subambient conditions are present (e.g., separation of CO(2) from natural gas), as at these low temperatures, one can take maximum advantage of the increased separation ability of the polymer materials while maintaining excellent transport characteristics. PMID- 20356205 TI - Structural, microstructural, and residual stress investigations of plasma-sprayed hydroxyapatite on Ti-6Al-4 V. AB - Plasma-spray (PS) is a classical technique usually employed to cover orthopaedic titanium implant surfaces with hydroxyapatite (HA - Ca(10)(PO(4))(6)(OH)(2)). The objective of the current study is to investigate the structure and microstructure of HA plasma-spray 50 mum thick coating on titanium alloy (Ti-6Al-4 V) and residual stress due to processing in the substrate and in HA coating. The structure of the coatings was determined by high-energy synchrotron X-ray diffraction in energy dispersive (HESXRD), selected area electron diffraction (saed), Scanning Electron Microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). No impurity phases in the HA were identified by HESXRD to keep away from the decomposition of HA at high temperature. hcp phase of HA substrate was detected with slight amorphous background. FTIR spectrum of a HA powder shows a typical spectrum for HA material with the characteristic phosphate peaks for HA at wavenumbers of 1090, 1052, 963, 602, and 573 cm(-1) are present. The morphology of HA powder observed by SEM exhibits grains of ca. 0.1 mum well adapted for cell proliferation. HA/Ti-6Al-4 V interface observed by cross-section scanning and transmission electron microscopy (TEM) presents microcracks. Residual stresses were analyzed by sin(2) Psi X-ray diffraction method on titanium substrates and HA coating. Although the Ti substrates are in a slightly tensile residual state, the coated ones show a compressive state. PMID- 20356206 TI - Synthesis and curing of hyperbranched poly(triazole)s with click polymerization for improved adhesion strength. AB - We successfully synthesized hyperbranched poly(triazole)s by in situ click polymerization of diazides 1 and triyne 2 monomers on different metal surfaces (copper, iron, and aluminum) and characterized their adhesive properties. Optimizations were performed to obtain high adhesive strength at different temperatures by analyzing the effects of curing kinetics, annealing temperature and time, catalyst, monomer ratio, surface conditions, alkyl chain length of diazides 1, etc. The adhesive bonding strength with metal substrate is 2 orders of magnitude higher than similar hyperbranched poly(triazole)s made by click polymerization and clearly higher than some commercial adhesives at elevated temperatures. With the same conditions, adhesives prepared on aluminum and iron substrates have higher adhesive strength than those prepared on copper substrate, and an excess of triyne 2 monomer in synthesis has greater adhesive strength than an excess of diazide 1 monomer. Tof-SIMS experiment was employed to understand these phenomena, and the existence of an interphase between the polymer and metal surface was found to be critical for adhesive bonding with thicker interphase (excess of triyne 2 monomer) and the higher binding energy between polymer atoms and substrate atoms (e.g., aluminum substrate) generating the higher bonding strength. In addition, the light-emitting property of synthesized polymers under UV irradiation can be used to check the failure mode of adhesive bonding. PMID- 20356207 TI - Photocatalytic activity of boron-modified titania under UV and visible-light illumination. AB - Nanosized boron(III) oxide-doped titania was prepared by homogeneous hydrolysis of titanium oxo-sulfate with urea in aqueous solutions in the presence of amorphous boron. The prepared samples were annealing at 700 degrees C. The structure of as-prepared samples was characterized by X-ray powder diffraction (XRD) and selected area electron diffraction (SAED) and surface area (BET) and porosity determination (BJH). The morphology and microstructure characteristics were obtained by scanning electron microscopy (SEM) and high-resolution electron microscopy (HRTEM). The method of UV/vis diffuse reflectance spectroscopy was employed to estimate band gap energies of the boron-doped titania. The photoactivity of the prepared samples was assessed by the photocatalytic decomposition of Orange II dye in an aqueous slurry during irradiation at 365 and 400 nm wavelength. The prepared titania samples doped with boron(III) oxide showed better photocatalytic activity in comparison with the reference TiO(2) sample. These photocatalysts showed better photocatalytic performance under visible-light irradiation. PMID- 20356208 TI - Superhard properties of rhodium and iridium boride films. AB - Very recently, the superhard properties of rhenium and ruthenium boride films were reported, this research being inspired by the discovery of the ReB(2) bulk superhardness. In this paper, we report the first successful deposition and characterization of rhodium and iridium boride films, other possible candidates for superhard materials. The films were prepared, applying the pulsed laser deposition technique, and studied by X-ray diffraction, scanning electron and atomic force microscopies, and Vickers microhardness. The refined structural parameters for RhB(1.1) and IrB(1.1) films were obtained. The RhB(1.1) film is characterized by the submicrometer crystallite size, whereas for the IrB(1.1) film, the crystallite size is in the tens of nanometers range, and this latter film presents a slightly preferred orientation along the [004] direction. Both the films exhibit very similar morphology, being composed of dense globular aggregate texture. The RhB(1.1) film presents a homogeneously textured surface with an average roughness of 20-50 nm, whereas the IrB(1.1) film possesses a finer texture with an average roughness of 20-30 nm. The intrinsic hardness of both films lies in the superhardness range: the 1.0 microm thick RhB(1.1) film possesses a hardness of 44 GPa, whereas the 0.4 microm thick IrB(1.1) film has a hardness of 43 GPa. PMID- 20356209 TI - Synthesis of mesoporous alumina from boehmite in the presence of triblock copolymer. AB - Mesoporous alumina was synthesized using commercial boehmite in the presence of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer Pluronic P123. Its calcination at 400 degrees C yielded gamma-alumina, in contrast to the ordered mesoporous alumina (OMA) obtained by hydrolysis of aluminum alkoxide in the presence of the same triblock copolymer. This synthesis afforded boehmite-based mesoporous alumina (BMA) with better adsorption properties and higher thermal stability in comparison to the alkoxide-based OMA, which remained amorphous after calcination below 900 degrees C. The BMA materials also exhibited higher amount of acidic and basic sites as evidenced by ammonia (NH(3)) and carbon dioxide (CO(2)) temperature programmed desorption (TPD), respectively. Dispersion of commercial boehmite precursor under microwave irradiation afforded BMA materials with similar surface characteristics as those of the corresponding BMA samples obtained under conventional conditions, but showing slightly lower acidity and better basic properties. Thus, the dispersion method of boehmite can be used to modify the surface properties of the resulting BMA samples without sacrificing their porosity. PMID- 20356210 TI - Metal oxide microrings with femtoliter capacity for Raman microspectroscopy. AB - A simple strategy, based on ultrafast heating of polystyrene microspheres infiltrated with a zinc acetate solution, is employed here for preparing ZnO microcontainers with femtoliter capacity. Their potential exploitation in micro Raman assays for basic studies in bio- and nanotechnology is tested in different proof-of-concept experiments concerning the in situ analysis of l-glutathione crystals and gold-yeast cytochrome c bioconjugates. The ZnO microcontainers are also used as scaffolds for atomic layer deposition of TiO(2) overlayers with a fine-tuning of thickness and morphology. The resulting ZnO/TiO(2) heterostructures are tested in different photocatalytic experiments involving degradation and laser-induced conversion of methylene blue. PMID- 20356211 TI - Thread as a versatile material for low-cost microfluidic diagnostics. AB - This paper describes a new and simple concept for fabricating low-cost, low volume, easy-to-use microfluidic devices using threads. A thread can transport liquid via capillary wicking without the need of a barrier; as it is stainable, it is also a desirable material for displaying colorimetric results. When used in sewing, threads have 3D passageways in sewed materials. The wicking property and flexibility of thread make it particularly suitable to fabricate 3D microfluidic devices. Threads can also be used with other materials (e.g., paper) to make microfluidic devices for rapid qualitative or semiquantitative analysis. These thread-based and thread-paper-based devices have potential applications in human health diagnostics, environmental monitoring, and food safety analysis, and are particularly appropriate for the developing world or remote areas, because of their relatively low fabrication costs. PMID- 20356212 TI - A monolayer-based setup for optical amplification. AB - Signal amplification has been demonstrated with surface-bound electrochromic complexes that can exist in one of two oxidation states (M2+/3+). Reaction of FeCl3 with covalently immobilized Os2+ complexes on glass substrates converts the metal centers from one oxidation state to the other. The formed Fe2+ reduces a series of Ru3+-based monolayers. The absorption of light is coupled with the oxidation state of the complexes and provides the output for the monolayer-based device. The gain of the setup can be controlled by the addition of a Fe2+ chelating ligand. PMID- 20356213 TI - Spontaneous hydrogen generation from organic-capped Al nanoparticles and water. AB - The development of technologies that would lead toward the adoption of a hydrogen economy requires readily available, safe, and environmentally friendly access to hydrogen. This can be achieved using the aluminum-water reaction; however, the protective nature and stability of aluminum oxide is a clear detriment to its application. Here, we demonstrate the spontaneous generation of hydrogen gas from ordinary room-temperature tap water when combined with aluminum-oleic acid core shell nanoparticles obtained via sonochemistry. The reaction is found to be near complete (>95% yield hydrogen) with a tunable rate from 6.4x10(-4) to 0.01 g of H2/s/g of Al and to yield an environmentally benign byproduct. The potential of these nanoparticles as a source of hydrogen gas for power generation is demonstrated using a simple fuel cell with an applied load. PMID- 20356214 TI - Dendrimer-assisted self-assembled monolayer of iron nanoparticles for vertical array carbon nanotube growth. AB - Self-assembled monolayers (SAMs) of iron oxide nanoparticles have been prepared using carboxylic-acid-terminated dendrimers. The iron-containing SAM was used as the catalyst for growth of vertical arrays of carbon nanotubes (CNTs). This approach has the potential for producing diameter controlled CNTs from premade catalyst nanoparticles as well as large scale production of CNTs by chemical vapor deposition. PMID- 20356215 TI - Free-standing carbon nanotube films as optical accumulators for multiplex SERRS attomolar detection. AB - A novel hybrid material comprising silver aggregates supported on the porous structure of a free-standing carbon nanotube film was devised and fabricated. This material readily allows filtration of large volumes of fluids, while retaining the active analytes on silver aggregates so that their characteristic surface-enhanced resonance Raman scattering signals could be registered. The direct identification of multiple analytes at the attomolar regime was readily achieved through their single-molecule spectra. PMID- 20356217 TI - Rapid microwave-assisted deposition of microwire patterns of nanoaluminum and nanosilver from colloids. AB - The rapid self-assembly of microwire patterns of 52-nm aluminum and 19-nm silver nanoparticles was demonstrated under microwave heating using novel surfactant solvent systems. Colloid solutions of 0.03% (w/v) nanoaluminum in 10% (v/v) poly(dimethylsiloxane)-acetone were used to self-assemble the microwire patterns of Al on glass substrates, which were dipped into the solution and held against the wall. Also, colloids of 0.001% (w/v) nanosilver prepared in an acetone solution of 33.3% (v/v) chloroform, 16.6% (v/v) poly(dimethylsiloxane), and 0.3% (v/v) Tween-20 were utilized for the deposition of microwire patterns under microwave heating at 51-55 degrees C. The evaporation-induced self-assembly of microwire patterns at the contact line was due to stick-slip dynamics. The rapid self-assembly of micropatterns of nanoaluminum and nanosilver was also demonstrated under microwave radiation within 2 min, and the width of the microwires was about 1-20 mum depending on the concentration of nanoparticles. PMID- 20356220 TI - Sequential coating of magnetic carbonyliron particles with polystyrene and multiwalled carbon nanotubes and its effect on their magnetorheology. AB - A two-step process for the sequential coating of magnetic carbonyliron (CI) particles with polystyrene (PS) and multiwalled carbon nanotubes (MWCNTs) was used to improve the sedimentation stability of micrometer-sized magnetic CI particles for magnetorheological (MR) applications under an applied magnetic field. The CI particles were initially coated with nanosized PS beads using an in situ dispersion polymerization method and then wrapped with a dense MWCNT nest through a solvent-casting method in a water/oil emulsion system. The morphology, MR performance, and sedimentation stability of the synthesized magnetic composite particles were examined. The composite particles showed enhanced MR characteristics and dispersion stability. PMID- 20356222 TI - Nanoparticle-induced controlled biodegradation and its mechanism in poly(epsilon caprolactone). AB - Poly(epsilon-caprolactone) (PCL)/layered silicate nanocomposites have been prepared via solution route. Two different organically modified nanoclays were used to compare the variation in properties based on organic modifications. The nanostructures, as observed from wide-angle X-ray diffraction and transmission electron microscopy, indicate intercalated and partially exfoliated hybrids depending on the nature of organic modification in nanoclay. The nanohybrids exhibit significant improvement in thermal and mechanical properties of the matrix as compared to neat polymer. The nanoclays act as nucleating agent for the crystallization of PCL. The biodegradability of pure PCL and its nanocomposites have been studied under controlled conditions in enzyme, pure microorganism (fungi), compost, Ganges water, and alkaline buffer solution. The rate of biodegradation of PCL has enhanced dramatically in nanohybrids and depends strongly on the media used. Scanning confocal, electron, and atomic force microscopes have used to demarcate the nature of biodegradation of pristine PCL and its nanocomposites. The change in biodegradation is rationalized in terms of the crystallization behavior and organic modification in nanoclays of the nanohybrids vis-a-vis the neat polymer. The extent of compatibility was measured quantitatively through the interaction parameter for two different nanoclays to compare and establish the reason for variation in their properties in nanohybrids. A biodegradation mechanism has been revealed for PCL and its nanocomposites through enzyme activity in varying pH environment. PMID- 20356226 TI - Noncovalent functionalization of boron nitride nanotubes with poly(p-phenylene ethynylene)s and polythiophene. AB - Boron nitride nanotubes (BNNTs) are functionalized and solubilized in organic solvents such as chloroform, methylene chloride, and tetrahydrofuran by using conjugated poly(p-phenylene ethynylene)s (PPEs) (polymers A and B) and polythiophene (polymer C) via a noncovalent functionalization approach through strong pi-pi stacking interactions between the conjugated polymers and BNNTs. The functionalization of BNNTs with PPEs enhanced planarization of PPEs with red shifts in both absorbance and emission of the composite materials with reference to free PPEs, whereas the functionalization of BNNTs with polythiophene disrupts the pi-conjugation, resulting in blue shifts in both the absorption and emission of the composite material. PMID- 20356227 TI - Fabrication of nickel oxide nanocomposite layer on a flexible polyimide substrate via ion exchange technique. AB - Continuous nickel oxide (NiO) nanocomposite layer on flexible polyimide (PI) substrate was prepared via an ion exchange technique. First, nickel(Pi) poly(amate) layers were formed on both surfaces of PI film through chemical surface modification of PI films in aqueous NaOH solution and then ion exchange in aqueous NiSO4 solution. Subsequently, hydrothermal treatment of the Ni2+ loaded PI films in an aqueous urea solution led to Ni(OH)2 formation in the surface-modified layers. Final thermal annealing in ambient air made Ni(OH)2 decompose to NiO, which diffused and aggregated to give continuous layers on both surfaces of PI film. The composite films were characterized by XRD, XPS, SEM, TEM, TGA, and DSC, respectively. Results from SEM and TEM measuring revealed that the NiO layers consisted of NiO nanoparticles with diameter ranging from 10 to 15 nm. Thermal properties of PI/NiO nanocomposite films were similar to those of host PI. This paper provides an effective methodology for the preparation of polymer/metal oxide nanocomposite films, which hold great promise toward the potential application in the areas of flexible microsensors and devices. PMID- 20356228 TI - Pt-decorated PdFe nanoparticles as methanol-tolerant oxygen reduction electrocatalyst. AB - The activity and selectivity of carbon-supported Pt-decorated PdFe nanoparticles in the oxygen reduction reaction (ORR) were investigated in the presence and absence of methanol. The Pt-decorated PdFe nanoparticles, which consist of a PdPt surface and a PdFe interior, were prepared by the galvanic reaction between PdFe/C alloy nanoparticles and PtCl4(2-) in aqueous solution. The presence of a Pt-enriched surface after the replacement reaction was independently confirmed by several microstructural characterization techniques and cyclic voltammetry. The catalyst with such heterogeneous architecture is catalytically more active than a bulk PdFePt alloy catalyst with the same overall composition. The observed enhancements in catalyst performance can be attributed to the lattice strain effect between the shell and core components. The Pt-decorated PdFe (PdFe@PdPt/C) catalyst also compares favorably with a commercial Pt/C catalyst with four times as much Pt in terms of ORR activity, cost, and methanol tolerance. PMID- 20356229 TI - Microreactor of Pd nanoparticles immobilized hollow microspheres for catalytic hydrodechlorination of chlorophenols in water. AB - A microreactor of Pd nanoparticles immobilized shell-corona hollow microspheres of poly[styrene-co-2-(acetoacetoxy) ethyl methacrylate-co-acrylamide] has been designed for catalytic hydrodechlorination (HDC) of chlorophenols in the sole solvent of water. The strategy of the combined use of the shell-corona hollow microspheres as microcapsule and catalyst scaffold endues the microreactor several advantages. First, the microreactor can be dispersed in the sole solvent of water and acts as a quasi-homogeneous catalyst for catalytic HDC of chlorophenols. Second, the reactant of chlorophenols can be highly concentrated within the hollow microspheres of the microreactor in the sole solvent of water. Third, the resultant product of phenol can be favorably excreted off the microreactor into water because of the polar difference between the reactant of chlorophenols and the product of phenol. Ascribed to the combined advantages, catalytic HDC of chlorophenols can be performed efficiently within the microreactor in the sole solvent of water at room temperature under atmosphere pressure. PMID- 20356235 TI - Protein-resistant NTA-functionalized polymer brushes for selective and stable immobilization of histidine-tagged proteins. AB - Protein-resistant polymeric coatings that allow highly selective immobilization of specific biomolecules are essential for biomedical applications such as microarrays, biosensing, heterogeneous catalysis, and bioengineering. Polymer brushes are particularly interesting for this purpose because their chemical structure and physical properties can easily be tailored to meet specific needs. This article explores the functionalization of two protein-resistant polymer brushes, poly(oligoethylene glycol methacrylate) (POEGMA) and poly(hydroxyethyl methacrylate) (PHEMA), with nitrilotriacetic acid (NTA) moieties that can complex histidine-tagged (His-tagged) proteins selectively and reversibly. Using fluorescence microscopy, IR spectroscopy, X-ray photoelectron spectroscopy, surface plasmon resonanace, and ellipsometry, we demonstrate that His-tagged green fluorescent protein can be immobilized on NTA brushes with high stability and loading. The loading saturation reached for NTA-POEGMA is higher than that for NTA-PHEMA because of increased swelling of the former brush. Despite this higher loading capacity, NTA-POEGMA remained highly protein-resistant, which shows its potential for "clean" and specific protein immobilization. Finally, we showed that the preserved protein resistance of NTA-POEGMA brushes can be used to generate well-defined binary biofunctional patterns via a simple protocol of incubations and washes. These patterns may find applications in cell arraying and screening. PMID- 20356236 TI - A novel electrolyte-responsive membrane with tunable permeation selectivity for protein purification. AB - A novel electrolyte-responsive membrane, RC-g-PSBMA, was successfully prepared from regenerated cellulose (RC) membrane through surface-initiated atom transfer radical polymerization (ATRP) of a zwitterionic monomer, sulfobetaine methacrylate (SBMA). Different degrees of polymerization for the grafted SBMA polymers (i.e., PSBMA) on the RC membrane were easily obtained by adjusting the ATRP reaction conditions. The electrolyte-responsive behavior of RC-g-PSBMA was first evaluated through the permeation experiments with sodium chloride (NaCl) solutions of different concentrations. It was found that the permeability of RC-g PSBMA showed a clear dependence on NaCl concentration in the solutions. To further examine the potential of RC-g-PSBMA for protein purification, bovine serum album (BSA) was chosen as a model protein and polystyrene nanoparticles (NPs) of different sizes were used as representative impurities in the solutions. The rejection rates of BSA and NPs by RC-g-PSBMA were examined with the solutions containing BSA and NPs at different NaCl concentrations. The results showed that the rejection rates of BSA were at a very low level regardless of the concentration of NaCl in the solutions, indicating that the membrane allowed BSA to permeate. However, the rejection rates of NPs of different sizes by RC-g-PSBMA changed remarkably with the concentration of NaCl in the solutions. The study has demonstrated the possibility to separate BSA from NPs of different sizes by using the same membrane but simply altering the concentration of NaCl in the solutions. Membranes with such properties will have a great potential for protein purification as well as for many other separation applications. PMID- 20356238 TI - Electrostatic layer-by-layer assembly of CdSe nanorod/polymer nanocomposite thin films. AB - Electrostatic layer-by-layer assembly was the basis for the synthesis of multilayer nanorod/polymer composite films. Cationic and water-soluble CdSe nanorods (NRs) were synthesized and partnered with anionic polymers including poly(sodium 4-styrenesulfonate) (PSS) and two polythiophene-based photoactive polymers, sodium poly[2-(3-thienyl)-ethoxy-4-butylsulfonate (PTEBS) and poly[3 (potassium-6-hexanoate)thiophene-2,5-diyl] (P3KHT). Controlled multilayer growth is shown through UV-vis spectroscopy, cross-sectional SEM and surface analytical techniques including atomic force microscopy. The formation of an intimate nanorod/conducting polymer bulk heterojunction is confirmed through cross sectional SEM, TEM, and scanning Auger analysis. A series of photovoltaic devices was fabricated on ITO electrodes using CdSe NRs in combination with PTEBS or P3KHT. A thorough device analysis showed that performance was limited by low short circuit current although charge transfer was confirmed in the ELBL nanocomposite thin films. PMID- 20356237 TI - Synthesis of triaxial LiFePO4 nanowire with a VGCF core column and a carbon shell through the electrospinning method. AB - A triaxial LiFePO4 nanowire with a multi wall carbon nanotube (VGCF:Vapor-grown carbon fiber) core column and an outer shell of amorphous carbon was successfully synthesized through the electrospinning method. The carbon nanotube core oriented in the direction of the wire played an important role in the conduction of electrons during the charge-discharge process, whereas the outer amorphous carbon shell suppressed the oxidation of Fe2+. An electrode with uniformly dispersed carbon and active materials was easily fabricated via a single process by heating after the electrospinning method is applied. Mossbauer spectroscopy for the nanowire showed a broadening of the line width, indicating a disordered coordination environment of the Fe ion near the surface. The electrospinning method was proven to be suitable for the fabrication of a triaxial nanostructure. PMID- 20356239 TI - Magnetron-sputtered Ag surfaces. New evidence for the nature of the ag ions intervening in bacterial inactivation. AB - DC-magnetron sputtering with an Ag target on textile surfaces produced Ag particles with sizes approximately 4.7 nm (+/-15%). Sputtering for 15 s led to Ag layers of 15-20 nm. The threshold sputtering time precluding airborne bacterial growth was about 60 s. In this case, the coating was approximately 40-50 nm thick and the cotton Ag loading was 0.0026 wt %. The Ag particle size did not vary significantly with sputtering time between 15 and 600 s. Only coatings above this thickness lead to bacterial inactivation. Ag/Pt targets with sputtering times<60 s did not increase the bactericide performance of the Ag cotton samples with respect to sputtering from an Ag target alone, as expected from the position of Pt respect to Ag in the electrochemical series (Galvanic effect). The Ag cotton deposition led to very thin metallic semitransparent gray color coatings. X-ray of the Ag cotton suggested the presence of amorphous and crystalline Ag species. By X-ray photoelectron spectroscopy (XPS), it was found that the amount of oxidized silver species on the cotton was similar for sputtering times of 60 and 600 s, but the total amount of Ag deposited was almost two times higher after 600 s sputtering. This suggests that the positive silver-ions were located mainly at the silver interface. The type of silver ions produced using the Ag/Pt sputtering was determined to be very similar at 15, 60, and 600 s with the silver ions produced with the Ag target. This explains the lack of an increased inhibitory effect of Pt during the inactivation of airborne bacteria when present in the Pt/Ag target with respect to the Ag target, because in both cases similar silver ionic species were found. PMID- 20356241 TI - Electrostatic interactions are not sufficient to account for chitosan bioactivity. AB - Recent studies involving chitosan interacting with phospholipid monolayers that mimic cell membranes have brought molecular-level evidence for some of the physiological actions of chitosan, as in removing a protein from the membrane. This interaction has been proven to be primarily of electrostatic origin because of the positive charge of chitosan in low pH solutions, but indirect evidence has also appeared of the presence of hydrophobic interactions. In this study, we provide definitive proof that model membranes are not affected merely by the charges in the amine groups of chitosan. Such a proof was obtained by comparing surface pressure and surface potential isotherms of dipalmitoyl phosphatidyl choline (DPPC) and dipalmitoyl phosphatidyl glycerol (DPPG) monolayers incorporating either chitosan or poly(allylamine hydrochloride) (PAH). As the latter is also positively charged and with the same charged functional group as chitosan, similar effects should be observed in case the electrical charge was the only relevant parameter. Instead, we observed a large expansion in the surface pressure isotherms upon interaction with chitosan, whereas PAH had much smaller effects. Of particular relevance for biological implications, chitosan considerably reduced the monolayer elasticity, whereas PAH had almost no effect. It is clear therefore that chitosan action depends strongly either on its functional uncharged groups and/or on its specific conformation in solution. PMID- 20356242 TI - Immunoassay on free-standing electrospun membranes. AB - For the purpose of immunoassay, electrospun membranes can be thought as the threadlike self-assembling of nano/microbeads. Nonwoven membranes of electrospun poly(epsilon-caprolactone) (PCL) fibers display excellent tenacity, flexibility and suitable surface energy. These PCL membranes exhibit easy handling in air, fast spreading, and wetting in aqueous solution, and rapid adsorption of protein molecules by hydrophobic interaction. After a fold-and-press process, the membrane porosity was reduced from approximately 75% to less than 10%, whereas the thickness increased from 5.3 to 280 microm. The resulting fluorescence signal from adsorbed protein increased>120x. With anti-HSA and HSA-FITC as an immunoassay model, a linear detection range from 500 ng/mL down to 1 ng/mL is obtained, with a detection of limit (LOD) of approximately 0.08 ng/mL. By comparison, conventional nitrocellulose and a 24.3 microm PCL fiber electrospun membrane displayed a much higher LOD of approximately 100 ng/mL. Immunoassay on free-standing electrospun membrane successfully combines the low-cost and simplicity of conventional membrane immunoassay, with the fast reaction speed and high sensitivity characteristic of magnetic nano/microbeads bioassays. PMID- 20356244 TI - Non-prefabricated nanocrystal mesoporous TiO2-based photoanodes tuned by a layer by-layer and rapid thermal process. AB - We describe a flexible and competent solution for fabrication of non prefabricated nanocrystal mesoporous TiO2-based photoanodes whose thicknesses are tunable from several hundreds of nanometers up to 12.4 microm. The combination of rapid thermal process and layer-by-layer spin-coating is successfully used to manipulate the structure and morphology of non-prefabricated nanocrystal mesoporous TiO2 films. The photovoltaic performances of mesoporous TiO2-based dye sensitized solar cells depended on the thickness and the annealing temperature of mesoporous photoanodes. We systematically investigated and noted that the non prefabricated nanocrystal mesoporous TiO2 films approximately 6.3 microm thick annealed at 500 degrees C displayed better features in the short-circuit current density and overall conversion efficiency of mesoporous TiO2-based dye-sensitized solar cells. PMID- 20356246 TI - Hybrid polymer-silicon proton conducting membranes via a pore-filling surface initiated polymerization approach. AB - An alternative approach for the creation of proton conducting platforms is presented. The methodology is based on the so-called "pore-filling concept", which relies on the filling of porous matrices with polyelectrolytes to obtain proton conducting platforms with high dimensional stability. Polymer-silicon composite membranes, with well-defined polyelectrolyte microdomains oriented normal to the plane of the membrane, were prepared using photoelectrochemically etched silicon as a microstructured scaffold. Ordered two-dimensional macroporous silicon structures were rendered proton conducting by filling the micropores via a surface-initiated atom transfer radical polymerization process. The morphological aspects, chemical stability, and performance of the hybrid assemblies were characterized by a set of techniques including scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, nuclear magnetic resonance and impedance spectroscopy, among others. The fabricated silicon-poly(sodium 2-acrylamide-2-methylpropane sulfonate) hybrid membranes displayed proton conductivities in the range of 1x10( 2) S/cm. This work illustrates the potential of hybrid polymer-silicon composite membranes synthesized by pore-filling surface-initiated polymerization to create proton conducting platforms in a simple and straightforward manner. Versatility and relative ease of preparation are two key aspects that make this approach an attractive alternative for the molecular design and preparation of proton conducting systems. PMID- 20356248 TI - Highly sensitive gold nanoparticle-based colorimetric sensing of mercury(II) through simple ligand exchange reaction in aqueous media. AB - A strategy for the rational design of a novel colorimetric sensor based on dithioerythritol-modified gold nanoparticles for the selective recognition of Hg2+ in aqueous media is presented. This approach relies on the combination of gold nanoparticles with Hg2+ through sulfur-Hg2+-sulfur interaction. The gold nanoparticles showed high selectivity toward Hg2+ with binding-induced red shift in the absorption spectra, with no response to major interfering cations such as Pb2+, Cd2+, and Cu2+ in the presence of ethylenediamine tetraacetic acid. The system responds to Hg2+ with a detection limit of 100 nM and might open a new avenue for the development of Hg2+ sensing probes. PMID- 20356252 TI - Optimization of the mechanical performance of bacterial cellulose/poly(L-lactic) acid composites. AB - Understanding the nature of the interface between nanofibers and polymer resins in composite materials is challenging because of the complexity of interactions that may occur between fibers and between the matrix and the fibers. The ability to select the most efficient amount of reinforcement for stress transfer, making a saving on both cost and weight, is also a key part of composite design. The use of Raman spectroscopy to investigate micromechanical properties of laminated bacterial cellulose (BC)/poly(l-lactic) acid (PLLA) resin composites is reported for the first time as a means for understanding the fundamental stress-transfer processes in these composites, but also as a tool to select appropriate processing and volume fraction of the reinforcing fibers. Two forms of BC networks are investigated, namely, one cultured for 3 days and another for 6 days. The mechanical properties of the latter were found to be higher than the former in terms of Young's modulus, stress at failure, and work of fracture. However, their specific Young's moduli (divided by density) were found to be similar. Young's modulus and stress at failure of transparent predominantly amorphous PLLA films were found to increase by 100 and 315%, respectively, for an 18% volume fraction of BC fibers. BC networks cultured for 3 days were shown to exhibit enhanced interaction with PLLA because of their higher total surface area compared, as measured by nitrogen adsorption, to the material cultured for 6 days. This enhanced interaction is confirmed by using the Raman spectroscopic approach, whereby larger band shift rates, of a peak initially located at 1095 cm(-1), with respect to both strain and stress, are observed, which is a quantitative measure of enhanced stress transfer. Thermal analysis (differential scanning calorimetry) and electron microscopy imaging (scanning electron microscopy) of the samples also confirms the enhanced coupling between the resin and the BC networks cultured for 3 days, compared to those cultured for 6 days. These results are shown to have implications for the use of BC networks for composite reinforcement, whereby less material can be used for the same specific mechanical properties. The technique also gives opportunities to study the interfaces in these composite materials in detail. PMID- 20356253 TI - Comment on biomimetic ultrathin whitening by capillary-force-induced random clustering of hydrogel micropillar arrays. PMID- 20356255 TI - A versatile biodegradable polymer with a thermo-reversible/irreversible transition. PMID- 20356256 TI - Bias-stress-stable solution-processed oxide thin film transistors. PMID- 20356257 TI - Design and fabrication of bimetallic colloidal "Janus" particles. PMID- 20356258 TI - Facile approach to large-scale synthesis of 1D calcium and titanium precipitate (CTP) with high electrorheological activity. PMID- 20356259 TI - Aging dynamics of solution-processed amorphous oxide semiconductor field effect transistors. PMID- 20356260 TI - Structure and property gradation from surface to bulk of Poly(l-lactic acid)/Poly(d-lactic acid) blended films as estimated from nanoscratch tests using scanning probe microscopy. PMID- 20356261 TI - Electroless plating of ultrathin films and mirrors of platinum nanoparticles onto polymers, metals, and ceramics. PMID- 20356262 TI - Contiguous petal-like carbon nanosheet outgrowths from graphite fibers by plasma CVD. PMID- 20356263 TI - Single-wall carbon nanotube latexes. PMID- 20356264 TI - Highly adhesive phenolic compounds as interfacial primers for bone fracture fixations. PMID- 20356265 TI - Robust superhydrophobic mats based on electrospun crystalline nanofibers combined with a silane precursor. AB - We demonstrate the fabrication of solvent-resistant, mechanically robust, superhydrophobic nanofibrous mats by electrospinning of poly(vinylidene fluoride) (PVDF) in the presence of inorganic silane materials. The solvent resistance and mechanical strength of nanofibrous mats were dramatically increased through the crystallization of as-spun PVDF fibers or incorporation of a tetraethyl orthosilicate (TEOS) sol into the nanofibrous matrix. The electrospun nanofibrous mats yielded a water contact angle of 156 degrees that did not vary with TEOS content. The solvent resistance and mechanical robustness of the electrospun mats were significantly enhanced through extensive cross-linking of TEOS, even after short PVDF annealing times. The interpenetrating polymer network, which embeds polymer chains in a TEOS network, allows the fabrication of robust functional nanofibers by combining semicrystalline polymers with electrospinning techniques. PMID- 20356266 TI - Effects of hydrogen in working gas on valence States of oxygen in sputter deposited indium tin oxide thin films. AB - X-ray photoelectron spectroscopy (XPS) and Rutherford backscattering spectroscopy elastic recoil detection analysis (RBS-ERDA) revealed that hydrogen in working gas for dc-plasma sputter deposition resided in indium tin oxide (ITO) films and generated the O(-) state seen as the suboxide-like O 1s peak in XPS. Growth of the suboxide-like O 1s peak was parallel with an increase of the resided hydrogen quantified by RBS-ERDA. The first-principles band structure calculation revealed that the electronic structure of In(2)O(3) crystal was realized typically for the most conductive as-deposited film grown in the gas containing hydrogen of 1%. The as-deposited film grown in the gas containing hydrogen of more than 1% exhibited rather high density but low mobility of carriers and showed the electronic structure above 4 eV originated from the O(-) state due to the resided hydrogen in addition to that of the most conducting one. Both well preserved In(2)O(3) band structure and proper concentration of the O(2-) vacancy are indispensable for achieving the highest conductivity; however, the O(-) state lowers efficiency of the carrier doping using the O(2-) vacancy in the lattice and increases density of the ionized scattering center for the carriers. PMID- 20356267 TI - Reinforced thermoplastic polyimide with dispersed functionalized single wall carbon nanotubes. AB - Molecular pi-complexes were formed from pristine HiPCO single- wall carbon nanotubes (SWCNTs) and 1-pyrene- N-(4-N'-(5-norbornene-2,3-dicarboxyimido)phenyl butanamide, 1. Polyimide films were prepared with these complexes as well as uncomplexed SWCNTs and the effects of nanoadditive addition on mechanical, thermal, and electrical properties of these films were evaluated. Although these properties were enhanced by both nanoadditives, larger increases in tensile strength and thermal and electrical conductivities were obtained when the SWCNT/1 complexes were used. At a loading level of 5.5 wt %, the T(g) of the polyimide increased from 169 to 197 degrees C and the storage modulus increased 20-fold (from 142 to 3045 MPa). The addition of 3.5 wt % SWCNT/1 complexes increased the tensile strength of the polyimide from 61.4 to 129 MPa; higher loading levels led to embrittlement and lower tensile strengths. The electrical conductivities (DC surface) of the polyimides increased to 1 x 10(-4) Scm(-1) (SWCNT/1 complexes loading level of 9 wt %). Details of the preparation of these complexes and their effects on polyimide film properties are discussed. PMID- 20356268 TI - Filter paper with selective absorption and separation of liquids that differ in surface tension. AB - Superhydrophobic and superoleophilic filter paper was successfully prepared by treating commercially available filter paper with a mixture of hydrophobic silica nanoparticles and polystyrene solution in toluene. Applications of the filter paper in separating liquids with low surface tensions such as oil and ethanol from water were investigated in detail. The oil uptake ability of the superhydrophobic filter paper was evaluated and the results show that the filter paper can selectively adsorb oil floating on a water surface or in aqueous emulsions. Furthermore, filtration of mixtures of oil and water through the paper can reduce the water content in the oil. Additionally, the filter paper can also extract ethanol from homogeneous aqueous solution. PMID- 20356269 TI - Cooperative binding of bifunctionalized and click-synthesized silver nanoparticles for colorimetric co(2+) sensing. AB - Bifunctionalized silver nanoparticles (triazole-carboxyl Ag NPs) were synthesized through a click reaction and have a cooperative effect on recognition of Co(2+), resulting in appreciable changes in color and absorption properties over other metal ions tested, including Fe(2+), Mn(2+), Hg(2+), Ni(2+), Cd(2+), Cu(2+), Zn(2+), Pb(2+), Li(+), Na(+), K(+), Cs(+). The functionalized silver nanoparticles became aggregated in solution in the present of Co(2+) through cooperative metal-ligand interaction. The colorimetric sensor allows a rapidly quantitive assay of Co(2+) down to the concentration of 7.0 x 10(-6) M. Moreover, the triazole-carboxyl AgNPs can be capable of evaluating the exceeding standard of Co(2+) in drinking water. PMID- 20356270 TI - Polythiophenes containing in-chain cobaltabisdicarbollide centers. AB - New cobalt(III) bis(dicarbollide) complexes covalently linked to two 2 oligothienyl units have been synthesized and electropolymerized in acetonitrile electrolyte in order to produce the corresponding polythiophene films containing in-chain metallic centers. The polymer films electrogenerated from the bithienyl (4b) and terthienyl (4c) derivatives display redox processes attributed to the Co(III)/Co(II) couple at ca. -1.1 V vs SCE and to the p-doping/undoping of the expected quaterthienyl and sexithienyl segments at ca. 0.8 V vs SCE. In contrast, the anodic oxidation of the thienyl (4a) derivative leads to passivation of the electrode surface. As the length of the oligothiophene substituents increases, the metallic and dicarbollide cage carbon atoms contributions in the HOMO decrease dramatically so that the highest occupied frontier orbitals of 4b and 4c can be considered as almost purely oligothiophene-based. From further UV-vis spectroscopy analysis, it is demonstrated that the polymer incorporating the sexithienyl segments is more conjugated than that with the quaterthienyl segments as the absorption maximum for the interband pi-pi* transition was observed at 410 and 448 nm for poly(4b) and poly(4c) respectively. Furthermore, these polymers display a more extended degree of conjugation than the parent oligothiophenes. Such features indicate a significant electronic delocalization through the cobaltabisdicarbollide moiety. Their conducting probe atomic force microscopy characterization indicates that poly(4b) and poly(4c) behave like heavily doped semiconductors rather than pure semiconductors. Mean conductivity values extracted from the current-voltage profiles are 1.4 x 10(-4) and 7.5 x 10(-4) S cm(-1) for poly(4b) and poly(4c), respectively. Such materials are found to be efficient for the electrocatalytic reduction of protons to dihydrogen, as exemplified for poly(4b). The overpotential for hydrogen evolution is significantly decreased by ca. 230 mV with respect to that obtained with the bare electrode (measured for a current density of 1.4 mA cm(-2) in the presence of 20 mM HBF(4)). PMID- 20356271 TI - Antimicrobial behavior of semifluorinated-quaternized triblock copolymers against airborne and marine microorganisms. AB - Semifluorinated-quaternized triblock copolymers (SQTCs) were synthesized by chemical modification of polystyrene-block-poly(ethylene-ran-butylene)-block polyisoprene ABC triblock copolymers. Surface characterization of the polymers was performed by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) analysis. The surface of the SQTC showed very high antibacterial activity against the airborne bacterium Staphylococcus aureus with >99 % inhibition of growth. In contrast in marine fouling assays, zoospores of the green alga Ulva settled on the SQTC, which can be attributed to the positively charged surface. The adhesion strength of sporelings (young plants) of Ulva and Navicula diatoms (a unicellular alga) was high. The SQTC did not show marked algicidal activity. PMID- 20356272 TI - Active and optically transparent tetracationic porphyrin/TiO(2) composite thin films. AB - Fluorescent tetracationic porphyrin (TMPyP) molecules have been incorporated into optically transparent TiO(2) thin films acting as a host material. The films, with a columnar structure and open pores, were prepared by electron evaporation at glancing angles (GAPVD). The open porosity of the films has been estimated by measuring a water adsorption isotherm with a quartz crystal monitor. TMPyP molecules were infiltrated in the host thin films by their immersion into water solutions at controlled values of pH. The state of the adsorbed molecules, the infiltration efficiency, and the adsorption kinetics were assessed by analyzing the optical response of the films by UV-vis absorption and fluorescence techniques. The infiltration efficiency was directly correlated with the acidity of the medium, increasing at basic pHs as expected from simple considerations based on the concepts of the point of zero charge (PZC) developed for colloidal oxides. By a quantitative evaluation based on the analysis of the UV spectra, the infiltration process has been described by a Langmuir type adsorption isotherm and an Elovich-like kinetics. The accessibility of the infiltrated molecules in the TMPyP/TiO(2) composite films is assessed by following the changes of their optical properties when exposed to the acid vapors and their subsequent recovery with time. PMID- 20356273 TI - Design of surfaces for liquid crystal-based bioanalytical assays. AB - Surface-induced ordering of liquid crystals (LCs) offers the basis of a label free analytical technique for the detection of surface-bound biomolecules. The orientation-dependent energy of interaction of a LC with a surface (anchoring energy of LC), in particular, is both sensitive to the presence of surface-bound molecules and easily quantified. Herein, we report a study that analyzes a simple model of twisted nematic LC systems and thereby identifies surfaces with LC anchoring energies in the range of 0.5 microJ/m(2) to 2.0 microJ/m(2) to be optimal for use with LC-based analytical methods. Guided by these predictions, we demonstrate that analytic surfaces possessing anchoring energies within this range can be fabricated with a high level of precision (< 0.1 microJ/m(2)) through formation of monolayers of organothiols (with omega-functional groups corresponding to oligoethyleneglycols and amines) on gold films deposited by physical vapor deposition at oblique angles of incidence. Finally, by using the human epidermal growth factor receptor (EGFR) as a model protein analyte, we have characterized the influence of the anchoring energies of the surfaces on the response of the LC to the presence of surface-bound EGFR. These results, when combined with (32)P-radiolabeling of the EGFR to independently quantify the surface concentration of EGFR, permit identification of surfaces that allow use of LCs to report surface densities of EGFR of 30-40 pg/mm(2). Overall, the results reported in this paper guide the design of surfaces for use in LC-based analytical systems. PMID- 20356274 TI - Strong hierarchically porous monoliths by pulsed current processing of zeolite powder assemblies. AB - Binderless hierarchically porous monoliths have been produced from silicalite-1 and ZSM-5 zeolite powders by a rapid and facile powder processing method where the zeolite powders are assembled in a graphite die and subjected simultaneously to a compressive pressure and a pulsed current. Pulsed current processing (PCP) or, as it is commonly called, spark plasma sintering, enables rapid thermal processing of zeolite powder assemblies with heating and cooling rates at 100 degrees C/minute or more, which results in the formation of strong powder bodies without any addition of secondary binders. Nitrogen adsorption measurements show that it is possible to form strong zeolite monoliths by PCP that maintain between 85 and 95% of the surface area of the as-received silicalite-1 and ZSM-5 powders. Line-broadening analysis of X-ray powder diffraction data by the Rietveld method and high-resolution electron microscopy showed that the formation of strong interparticle bonds is associated with a local amorphization reaction at the interfacial contact points between the zeolite particles. The PCP-treated binderless ZSM-5 monoliths display a high selectivity in xylene isomer separation. PMID- 20356275 TI - Synthesis and characterization of ethylene glycol substituted poly(phenylene vinylene) derivatives. AB - We report the synthesis of a series of water-soluble, fluorescent, conjugated polymers via the Gilch reaction with an overall yield greater than 40%. The yield for the Gilch reaction decreases with the increase in the length of the side chain (ethylene glycol repeat units), presumably due to the steric effects inhibiting the linking of monomeric units. The hydrophilic side chain enhances the solubility of the polymer in water and concomitantly leads to a side-chain dependent conformation and solvent-dependent quantum efficiency. An increase in the ethylene glycol repeat units on the polymer side chain structure results in changes in chain packing; hence, the crystallinity evolves from semicrystalline to liquid crystalline to completely amorphous. An increase in the length of the side chain leads to changes in the polymer-solvent interaction as manifested in the photophysical properties of these polymers. These novel polymers exhibit two glass transition temperatures, which can be readily rationalized by differences in microstructure when casted from hydrophobic and hydrophilic solvents. Cyclic voltammograms of polymer 1d-3d suggest two-electron transfer, as compared to P1 which has one complete redox pair. The potential of having a nanoscaled domain structure and stabilizing two electrons on a polymer chain signifies the potential of these polymers in fabricating electronic and photovoltaic devices. PMID- 20356277 TI - Synthesis of iron oxide nanoparticles with control over shape using imidazolium based ionic liquids. AB - Ionic liquid (IL)-coated iron oxide nanoparticles (IONs) were synthesized by the thermal decomposition of Fe(CO)(5) in an IL/DMF solvent system in the absence of stabilizing surfactants at 90 degrees C for 1 h. The IL, [omim][BF(4)], could regulate the shape and allow the preparation of anisotropic IONs, such as barlike and wirelike nanoparticles. The barlike IONs prepared using this method showed good superparamagnetic behavior in a magnetic field and a MR contrast enhancement effect in a MR scanner. PMID- 20356276 TI - Immobilizing enzymes onto electrode arrays by hydrogel photolithography to fabricate multi-analyte electrochemical biosensors. AB - This paper describes a biomaterial microfabrication approach for interfacing functional biomolecules (enzymes) with electrode arrays. Poly (ethylene glycol) (PEG) hydrogel photopatterning was employed to integrate gold electrode arrays with the enzymes glucose oxidase (GOX) and lactate oxidase (LOX). In this process, PEG diacrylate (DA)-based prepolymer containing enzyme molecules as well as redox species (vinylferrocene) was spin-coated, registered, and UV cross linked on top of an array of gold electrodes. As a result, enzyme-carrying circular hydrogel structures (600 microm diameter) were fabricated on top of 300 microm diameter gold electrodes. Importantly, when used with multiple masks, hydrogel photolithography allowed us to immobilize GOX and LOX molecules on adjacent electrodes within the same electrode array. Cyclic voltammetry and amperometry were used to characterize biosensor electrode arrays. The response of the biosensor array was linear for up to 20 mM glucose with sensitivity of 0.9 microA cm(-2) mM(-1) and 10 mM lactate with sensitivity of 1.1 microA cm(-2) mM( 1). Importantly, simultaneous detection of glucose and lactate from the same electrode array was demonstrated. A novel strategy for integrating biological and electrical components of a biosensor described in this paper provides the flexibility to spatially resolve and register different biorecognition elements with individual members of a miniature electrode array. Of particular interest to us are future applications of these miniature electrodes for real-time monitoring of metabolite fluxes in the vicinity of living cells. PMID- 20356278 TI - Thermally induced phase transition of glucose-sensitive core-shell microgels. AB - Four series of poly(N-isopropylacrylamide) (PNIPAM) (core)/poly(N isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-AAPBA)) (shell) microgels were synthesized by the modification of PNIPAM (core)/poly(N isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) (shell) microgels with 3 aminophenylboronic acid (APBA). Their thermosensitive behaviors were studied by dynamic light scattering. Two or three phase transitions were detected depending on the shell thickness. These transitions were confirmed by the first derivative plot of the turbidity data. The first transition occurring at about 17 degrees C was assigned to that of the P(NIPAM-AAPBA) shell, whereas the second and third ones, which occur at about 22 and 28 degrees C, respectively, were assigned to that of the PNIPAM core. These results indicate that the influences of a shrunk P(NIPAM-AAPBA) shell on the different parts of the PNIPAM core are different. As the outer part, or the "shell" part of the PNIPAM core, directly connects with the P(NIPAM-AAPBA) shell, its phase transition temperature is reduced to a larger degree as compared with that of the inner part, or the "core" part. Glucose induced swelling was observed for all the microgels, indicating their glucose sensitivity. However, the degree of glucose-induced swelling is much smaller than that of the pure P(NIPAM-AAPBA) microgels. PMID- 20356279 TI - Magnetoresponsive smart capsules formed with polyelectrolytes, lipid bilayers and magnetic nanoparticles. AB - Magnetoresponsive smart capsules formed with polyelectrolytes, lipid bilayers and magnetic nanoparticles were fabricated by a colloid-templating technique. Melamine-formaldehyde core particles with polyelectrolyte multilayer shell were prepared by layer-by-layer assembly. Magnetite (Fe(3)O(4)) nanoparticles were selectively deposited on the capsular surface by aqueous solution deposition using Pd catalysts. Hollow capsules were obtained by the removal of the melamine formaldehyde core particles. Vibrating sample magnetometer (VSM) measurement of the capsules revealed the ferromagnetic behavior of deposited Fe(3)O(4) nanoparticles. Alternating magnetic field irradiation generates heat in the capsular dispersion. Additional lipid bilayer coating was carried out on the obtained hollow capsules. Dye molecules were loaded by exploiting the temperature dependence of the lipid membrane permeability. An encapsulated dye was released on-demand by irradiation with an alternating magnetic field, due to a phase transition in the lipid membrane, induced by heating of the magnetic nanoparticles. The magnetically induced release is attributed to the phase transition of the lipid membrane, caused by heat of Fe(3)O(4) nanoparticles under magnetic stimuli, and not to rupture of the capsules. PMID- 20356280 TI - Aluminum microstructures on anodic alumina for aluminum wiring boards. AB - The paper demonstrates simple methods for the fabrication of aluminum microstructures on the anodic oxide film of aluminum. The aluminum sheets were first engraved (patterned) either by laser beam or by embossing to form deep grooves on the surface. One side of the sheet was then anodized, blocking the other side by using polymer mask to form the anodic alumina. Because of the lower thickness at the bottom part of the grooves, the part was completely anodized before the complete oxidation of the other parts. Such selectively complete anodizing resulted in the patterns of metallic aluminum on anodic alumina. Using the technique, we fabricated microstructures such as line patterns and a simple wiring circuit-board-like structure on the anodic alumina. The aluminum microstructures fabricated by the techniques were embedded in anodic alumina/aluminum sheet, and this technique is promising for applications in electronic packaging and devices. PMID- 20356281 TI - Nanostructured ruthenium oxide electrodes via high-temperature molecular templating for use in electrochemical capacitors. AB - Ruthenium oxide is a model pseudocapacitive materials exhibiting good electronic and protonic conduction and has been shown to achieve very high gravimetric capacitances. However, the capacitance of thermally prepared ruthenium oxide is generally low because of low protonic conductivity resulting from dehydration of the oxide upon annealing. High-temperature processing, however also produces the electrically conducting ruthenium oxide rutile phase, which is of great interest for electrochemical capacitors. Here, unusual electrochemical characteristics were obtained for thermally prepared ruthenium oxide when fabricated in the presence of alkyl-thiols at high temperature. The performance characteristics have been attributed to enhanced multifunctional properties of the material resulting from the novel processing. The processing method relies on a simple, solution-based strategy that utilizes a sacrificial organic template to sterically direct hierarchical architecture formation in electro-active ruthenium oxide. Thin films of the templated RuO(2) exhibit energy storage characteristics comparable to hydrous ruthenium oxide materials formed under dramatically different conditions. Extensive materials characterization has revealed that these property enhancements are associated with the retention of molecular-sized metal oxide clusters, high hydroxyl concentrations, and formation of hierarchical porosity in the ruthenium oxide thin films. PMID- 20356282 TI - Design and fabrication of nanopillar patterned au textures for improving nanotribological performance. AB - Fast development of micro/nanoelectromechanical systems (MEMS/NEMS) and high density storage technology (HDT) have stimulated the development of new materials that require hydrophobic surfaces with low adhesion and friction. Micro/nanohierarchical structures and chemical modification are two useful methods for improving nanotribological properties of mechanical components. In this study, Au surfaces with micro/nanohierarchical structures were prepared by replication of micropatterened silicon surfaces using PDMS and self-assembly of alkanethiol [CH(3)(CH(2))(9)SH] to create hydrophobic micro/nanohierarchical structures and to improve nanotribological properties of MEMS/NEMS. The effects of nanoscaled roughness (including pillar height and pillar fractional surface coverage) and chemical modification on the wetting and nanotribological properties of surfaces were systemically investigated. Results show that with the increasing of nanoscale roughness and lowering of surface energy, the surface becomes more hydrophobic, and the adhesive force and friction force are reduced greatly. PMID- 20356283 TI - Chemically directed immobilization of nanoparticles onto gold substrates for orthogonal assembly using dithiocarbamate bond formation. AB - Dithiocarbamate-mediated bond formation combined with soft lithography was used for the selective immobilization of amine-functionalized silica nanoparticles on gold substrates. The available amine groups on the upper surface of the immobilized silica nanoparticles were further utilized for postdeposition of additional materials including particles, dyes, and biomolecules. The robustness of dithiocarbamate-mediated immobilization enables orthogonal assembly on surfaces via selective removal of the masking thiol ligands using iodine vapor etching followed by further functionalization. PMID- 20356284 TI - Phase separation as a tool to control dispersion of multiwall carbon nanotubes in polymeric blends. AB - Conducting polymeric materials with stable phase microstructures have a range of potential applications. In this work, it is investigated whether phase separation in polymer blends can be used as a tool to create well dispersed conducting filler rich domains in 3D with controlled morphology, potentially resulting in more effective percolation. The effect of amine functionalized multiwall carbon nanotubes (NH(2)-MWCNTs) on the thermally induced phase separation processes in poly[(alpha-methyl styrene)-co-acrylonitrile]/poly(methyl methacrylate) (PalphaMSAN/PMMA) blends was monitored by melt rheology, conductivity spectroscopy, and microscopic techniques. Electron microscopic images revealed that the phase separation resulted in a heterogeneous distribution of NH(2) MWCNTs in the blends. The migration of NH(2)-MWCNTs is controlled by the thermodynamic forces that drive phase separation and led to an increase in their local concentration in a specific phase resulting in percolative "network-like" structure. Conductivity spectroscopy measurements demonstrated that the blends with 2 wt % NH(2)-MWCNTs that showed insulating properties for a one phasic system revealed highly conducting material in the melt state (two phasic) as a result of phase separation. By quenching this morphology, a highly conducting material with controlled dispersion of MWCNTs can be achieved. Furthermore, the role of NH(2)-MWCNTs in stabilizing the PMMA droplets against flow induced coalescence in 85/15 PalphaMSAN/PMMA blends was also established for the first time. It was observed that at a typical loading of 1.25 wt % NH(2)-MWCNTs the coalescence was completely suppressed on a practical time scale. PMID- 20356285 TI - Influences of current density on tribological characteristics of ceramic coatings on ZK60 Mg alloy by plasma electrolytic oxidation. AB - Current density is a key factor of plasma electrolytic oxidation process. Its influences on structure, mechanical, and tribological characteristics of ceramic coatings on ZK60 Mg alloy by pulsed bipolar microplasma oxidation in Na(3)PO(4) solution were studied in this paper. Thickness, structure, composition, mechanical property, and tribological characteristics of the coatings were studied by eddy current coating thickness gauge, scanning electron microscope (SEM), X-ray diffraction (XRD), nanoindentation measurements, and ball-on-disk friction testing. The results show that all the coatings prepared under different current densities are composed of MgO phase. The amount of MgO phase, thickness and friction coefficient of the coatings increased with the increasing current density. Among three ceramic coatings produced under three current densities, the coating produced under the current density of 7 A/dm(2) got the highest nanohardness and lowest wear rate with the value of 1.7 GPa and 1.27 x 10(-5) mm(3)/Nm. PMID- 20356286 TI - Layer-by-layer-assembled high-performance broadband antireflection coatings. AB - Nanoparticles are indispensable ingredients of solution-processed optical, dielectric, and catalytic thin films. Although solution-based methods are promising low-cost alternatives to vacuum methods, they can have significant limitations. Coating uniformity, thickness control, roughness control, mechanical durability, and incorporation of a diverse set of functional organic molecules into nanoparticle thin films are major challenges. We have used the electrostatic layer-by-layer assembly technique to make uniform, conformal multistack nanoparticle thin films for optical applications with precise thickness control over each stack. Two particularly sought-after optical applications are broadband antireflection and structural color. The effects of interstack and surface roughness on optical properties of these constructs (e.g., haze and spectral response) have been studied quantitatively using a combination of Fourier transform methods and atomic force microscopy measurements. Deconvoluting root mean-square roughness into its large-, intermediate-, and small-scale components enables enhanced optical simulations. A 4-stack broadband antireflection coating (<0.5% average reflectance in the visible range, and 0.2% haze) composed of alternating high-index (n approximately 1.96) and low-index (n approximately 1.28) stacks has been made on glass substrate. Films calcinated at 550 degrees C endure a one-hour-long cloth cleaning test under 100 kPa normal stress. PMID- 20356287 TI - Effect of graphene oxide on the properties of its composite with polyaniline. AB - Graphene oxide, a single layer of graphite oxide (GO), has been used to prepare graphene oxide/polyaniline (PANI) composite with improved electrochemical performance as supercapacitor electrode by in situ polymerization using a mild oxidant. The composites are synthesized under different mass ratios, using graphite as start material with two sizes: 12 500 and 500 mesh. The result shows that the morphology of the prepared composites is influenced dramatically by the different mass ratios. The composites are proposed to be combined through electrostatic interaction (doping process), hydrogen bonding, and pi-pi stacking interaction. The highest initial specific capacitances of 746 F g(-1) (12 500 mesh) and 627 F g(-1) (500 mesh) corresponding to the mass ratios 1:200 and 1:50 (graphene oxide/aniline) are obtained, compared to PANI of 216 F g(-1) at 200 mA g(-1) by charge-discharge analysis between 0.0 and 0.4 V. The improved capacitance retention of 73% (12 500 mesh) and 64% (500 mesh) after 500 cycles is obtained for the mass ratios 1:23 and 1:19 compared to PANI of 20%. The enhanced specific capacitance and cycling life implies a synergistic effect between two components. This study is of significance for developing new doped PANI materials for supercapacitors. PMID- 20356288 TI - Efficient bulk heterojunction solar cells with poly[2,7-(9,9-dihexylfluorene)-alt bithiophene] and 6,6-phenyl C61 butyric acid methyl ester blends and their application in tandem cells. AB - We present herein efficient bulk heterojunction (BHJ) solar cells via mixing poly[2,7-(9,9-dihexylfluorene)-alt-bithiophene] (F6T2) and 6,6-phenyl C61 butyric acid methyl ester (PCBM) with variable weight ratios. The photo-physics and morphology of F6T2:PCBM blend films and the electrical characteristics of their corresponding single cells were studied in details by changing PCBM concentration. The complete photoluminescence quenching of F6T2 emission occurs with only a small fraction of PCBM blended, demonstrating effective photoinduced charge transfer between F6T2 and PCBM. Morphology images from atomic force microscopy and scanning electron microscopy (SEM) reveal that the phase separation in F6T2:PCBM blend films becomes pronounced with the increase of PCBM concentration, resulting in the increased fill factor from 25.2% (1:1) to 56.9% (1:6). A SEM image also shows the phase separation is within the range of 10 - 20 nm. With the optimized F6T2:PCBM weight ratio (1:2), the single cell exhibits a highest power conversion efficiency of 2.46% due to the balance of light absorption and charge transport. Finally, the polymer-small molecule tandem cells are constructed using F6T2:PCBM BHJ as the bottom cell and copper phthalocyanine (CuPc):fullerene (C(60)) as the top cell. The open-circuit voltage (V(oc)) of tandem cell (1.27 V) is equal to the summation of the V(oc) values of the bottom cell (0.86 V) and the top cell (0.43 V). PMID- 20356289 TI - Hierarchical organization and catalytic activity of high-surface-area mesoporous ceria microspheres prepared via hydrothermal routes. AB - Mesoporous Ce(OH)CO(3) microspheres with flowerlike three-dimensional (3D) hierarchical structure were successfully synthesized via different hydrothermal systems, including glucose/acrylic acid, fructose/acrylic acid, glucose/propanoic acid, and glucose/n-butylamine systems. After Ce(OH)CO(3) microspheres were calcined, mesoporous CeO(2) microspheres with the same flowerlike morphology as Ce(OH)CO(3) microspheres were obtained. Especially, flowerlike CeO(2) microspheres prepared via the glucose/acrylic acid system are composed of many interconnected mesoporous petal-like nanosheets with thicknesses of 40-60 nm and have high surface area (211 m(2) g(-1)), large pore volume (0.32 cm(3) g(-1)), and narrow pore size distribution ( approximately 3.8 nm in diameter). A possible formation mechanism of Ce(OH)CO(3) microspheres is proposed: the large N containing organic compounds in situ produced in the above reaction systems played a crucial role in controlling the assembly of Ce(OH)CO(3) building blocks into the flowerlike Ce(OH)CO(3) microspheres. For trichloroethylene combustion, flowerlike CeO(2) microspheres were found to exhibit much higher catalytic activity than general CeO(2) prepared with the conventional methods and the T(10%) and T(90%) were as low as 100 and 204 degrees C, respectively. PMID- 20356290 TI - Self-assembled block copolymer thin films as water filtration membranes. AB - Nanoporous membranes containing monodisperse pores of 24 nm diameter are fabricated using poly(styrene-b-lactide) block copolymers to template the pore structure. A 4 mum thin film of the block copolymer is cast onto a microporous membrane that provides mechanical reinforcement; by casting the copolymer film from the appropriate solvents and controlling the solvent evaporation rate, greater than 100 cm(2) of a thin film with polylactide cylinders oriented perpendicular to the thin dimension is produced. Exposing the composite membrane to a dilute aqueous base selectively etches the polylactide block, producing the porous structure. The ability of these pores to reject dissolved poly(ethylene oxide) molecules of varying molecular weight matches existing theories for transport through small pores. PMID- 20356291 TI - Influence of clearcoats on the spectral and physical properties of electrochemically formed colored passive layers on zirconium. AB - We report on the application and characterization of two commercial polymer clearcoats to electrochemically formed colored passive layers on zirconium with the aim of providing effective physical and chemical protection while allowing the unique and colorful appearance of the colored passive layers to show through. Thin layers of an acrylic automotive clearcoat ( approximately 3.5 mum thick) and an epoxy marine clearcoat ( approximately 8.5 mum thick) were applied to the colored zirconium surfaces via spin coating and were found to only slightly modify their visual properties, maintaining their vibrant colors. As clearcoats were applied, the outer surface was found to be smoother than the surface of colored zirconium, thereby reducing potential wear from friction and the adhesion of fine dirt. Clearcoat-protected samples were found to wet less easily than colored zirconium alone, thus furthering its protection against damage in ambient (surface weathering) and aqueous media (aqueous corrosion). Light microscopy experiments at a 50-400x magnification revealed the absence of any structural defects in the clearcoats. The clearcoats show the ability to protect colored zirconium from physical and chemical damage, with the automotive clearcoat exhibiting superior adhesion. Our electrochemical coloring combined with the application of clearcoats creates a novel system that possesses unique esthetic properties while simultaneously offering protection against various forms of environmental damage such as weathering or corrosion. PMID- 20356292 TI - Photoemission spectroscopy of tethered CdSe nanocrystals: shifts in ionization potential and local vacuum level as a function of nanocrystal capping ligand. AB - We report the characterization of the frontier orbital energies and interface dipole effects for bare and ligand-capped 3.6 and 6.0 nm diameter CdSe nanocrystals (NC) tethered to smooth gold substrates, using He(I) and He(II) UV photoemission spectroscopy. Changes in the ionization potential (IP) of the NCs and local effective work function of the films were explored as a function of the dipolar nature of the NC capping ligands. The addition of thiol-capping ligands 1 hexanethiol, 1-benzenethiol, and 4-fluorothiophenol to both sizes of NCs produces negligible shifts in energy offset between the high kinetic energy edge of the CdSe NCs and the gold substrate Fermi energy. However, the local vacuum level and IP of the nanocrystal layer are altered by as much as 0.3 eV. We demonstrate the importance of determining both the local vacuum level and the high kinetic energy edge of a tethered NC sample. These studies demonstrate a method that can be used in the future to characterize the frontier orbital energy offsets for modified or unmodified nanocrystalline films, in which the NCs are incorporated into host materials, for applications ranging from photovoltaics to light-emitting diodes. PMID- 20356293 TI - Imidazolium ionic liquids as antiwear and antioxidant additive in poly(ethylene glycol) for steel/steel contacts. AB - Three imidazolium-based ionic liquids containing sterically hindered phenol groups were synthesized. The cation was 1-(3,5-ditert-butyl-4-hydroxybenzyl)-3 methyl-imidazolium, and the anions were tetrafluoroborates, hexafluorophosphates, and bis(trifluoromethylsulfonyl)imide. The physical properties of the synthetic products and of poly(ethylene glycol) (PEG) with the additive were evaluated. The oxidative stability of 0.5 wt % 1-(3,5-di-tert-butyl-4-hydroxybenzyl)-3-methyl imidazolium hexafluorophosphates in PEG were assessed via rotating bomb oxidation test (RBOT), thermal analysis, and copper strip test. The tribological behaviors of the additives for PEG application in steel/steel contacts were evaluated on an Optimol SRV-IV oscillating reciprocating friction and wear tester as well as on MRS-1J four-ball testers. The worn steel surface was analyzed by a JSM-5600LV scanning electron microscope and a PHI-5702 multifunctional X-ray photoelectron spectrometer. RBOT test, thermal analysis, and copper strip test results revealed that synthesized ionic liquids possessed excellent antioxidant properties. Tribological application results revealed that these could effectively reduce friction and wear of sliding pairs compared with the PEG films used without the additives. Specifically, (BHT-1)MIMPF(6) exhibited better antiwear properties at an optimum concentration of 1 wt %. At this level, its antiwear property significantly improved by 100 times with respect to using just the PEG base oil. Boundary lubrication films composed of metal fluorides, organic fluorines, organic phosphines, and nitride compounds were formed on the worn surface, which resulted in excellent friction reduction and antiwear performance. PMID- 20356294 TI - Using light-induced thermocleavage in a roll-to-roll process for polymer solar cells. AB - We report on the use of intense visible light with a narrow spectral distribution matched to the region where the conjugated polymer material absorbs to selectively heat the active material and induce thermocleavage. We show a full roll-to-roll process, leading to complete large-area polymer solar cell modules using light-induced thermocleavage. The process employs full solution processing in air for all five layers in the device and does not employ indium-tin oxide or vacuum processing. The process steps were carefully analyzed using X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, attenuated total reflectance infrared, and transmission/reflection UV-vis techniques. PMID- 20356295 TI - Control of particle size of pt and pt alloy electrocatalysts supported on carbon black by the nanocapsule method. AB - Monodisperse Pt and Pt-M (M = Co, Ru) alloy nanoparticles supported on carbon black (Pt/CB, Pt(2)Ru(3)/CB, Pt(3)Co/CB) were prepared by the nanocapsule method. We have succeeded in controlling the particle size simply by changing the molar ratio of metal precursor(s) to surfactant (M/S) in the preparation, with the other conditions being identical. The particle size was well-controlled between 2.0 and 4.5 nm with a metal loading level of 50 wt % for all catalysts. The compositions of the alloy particles were close to the projected values, with a small standard deviation, i.e., <3.1 atom % for Pt(2)Ru(3) and 1.4 atom % for Pt(3)Co. It was also found that these alloys were in the form of the corresponding solid solutions with the fcc structure. PMID- 20356296 TI - Growth, microstructure, and infrared-ultraviolet optical conductivity of La(0.5)Sr(0.5)CoO(3) nanocrystalline films on silicon substrates by pulsed laser deposition. AB - La(0.5)Sr(0.5)CoO(3) (LSCO) nanocrystalline (nc) films have been directly grown on silicon wafers under different substrate temperatures by pulsed laser deposition. The X-ray diffraction analysis indicate that the films are polycrystalline with the pure perovskite phase at higher substrate temperatures. The columnar growth formation with the nanocrystalline structure in the films has been confirmed by microscopy experiments. Infrared-ultraviolet optical properties of the LSCO films have been investigated with the aid of spectroscopic ellipsometry (SE). Dielectric function in the photon energy range of 1.1-3.1 eV (400-1100 nm) has been extracted by reproducing the experimental data with a Lorentz oscillator model. It is found that the real part is decreased from 4.7 to -0.7 at the near-infrared region with increasing substrate temperature. The optical conductivity shows a different variation trend for the lower and higher growth temperatures, respectively. Note that the films deposited above 650 degrees C exhibit the well-defined metallic phase behavior. The discrepancies could be mainly ascribed to different crystalline structure and surface morphology. The present results may be crucial for future applications of ferromagnetic-based optoelectronic and spin-electronic devices. PMID- 20356297 TI - Poly(ethylene glycol)-based thiol-ene hydrogel coatings-curing chemistry, aqueous stability, and potential marine antifouling applications. AB - Photocured thiol-ene hydrogel coatings based on poly(ethylene glycol) (PEG) were investigated for marine antifouling purposes. By varying the PEG length, vinylic end-group, and thiol cross-linker, a library of hydrogel coatings with different structural composition was efficiently accomplished, with or without ester linkages. The thiol-methacrylate and thiol-allyl systems were evaluated with respect to curing, degradation, as well as antifouling properties. Methacrylate based systems exhibited homopolymerization, whereas allyl-based systems reacted more selectively through thiol-ene couplings reaction. The ester-free hydrogels elucidated higher hydrolytic stability whereas longer PEG chains accelerated the degradation process. The antifouling properties were evaluated by protein adsorption with Bovine serum albumin (BSA) and bioassays with the marine bacteria, Cobetia marina, and the marine diatom, Amphora coffeaeformis; in all tests, longer PEG lengths improved the antifouling properties. PMID- 20356298 TI - Highly condensed fluorinated methacrylate hybrid material for transparent low kappa passivation layer in LCD-TFT. AB - Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation. PMID- 20356299 TI - All-aramid composites by partial fiber dissolution. AB - The area of self-reinforced polymer composites is one of the fastest growing areas in engineering polymers, but until now these materials have been mainly developed on the basis of thermoplastic fibers of moderate performance. In this work, we report on a new type of self-reinforced composites based on high performance aramid fibers to produce an "all-aramid" composite by applying a surface-dissolution method to fuse poly(p-phenylene terephthalamide) (PPTA) fibers together. After immersion in concentrated (95%) sulphuric acid (H(2)SO(4)) for a selected period of time, partially dissolved fiber surfaces were converted into a PPTA interphase or matrix phase. Following extraction of H(2)SO(4) and drying, a consolidated all-aramid composite was formed. The structure, mechanical and thermal properties of these single-polymer composites were investigated. Optimum processing conditions resulted in unidirectional composites of high reinforcement content (approximately 75 vol %) and good interfacial bonding. The all-aramid composites featured a Young's modulus of approximately 65 GPa at room temperature, and a tensile strength of 1.4 GPa, which are comparable with or exceed the corresponding values of conventional aramid/epoxy composites. However, since fiber, matrix and interphase in all-aramid composites are based on the same high-temperature resistant PPTA polymer, a high modulus of approximately 50 GPa was maintained up to 250 degrees C, demonstrating the potential of these materials for high-temperature applications. PMID- 20356300 TI - Microwave absorption behavior of core-shell structured poly (3,4-ethylenedioxy thiophene)-barium ferrite nanocomposites. AB - The present paper reports the complex permittivity, permeability, and microwave absorption properties of core shell type poly (3,4-ethylenedioxy thiophene) (PEDOT) nanocomposite with barium ferrite, synthesized by in situ emulsion polymerization, in the 12.4-18 GHz frequency range. High-resolution transmission electron microscopy (HRTEM) studies reveal the formation of core-shell type morphology with ferrite particles (60-80 nm) as the center while the polymer (PEDOT) formulates the outer shell of the composite. The presence of barium ferrite nanoparticles in the polymer matrix includes the magnetic losses, which mainly arise from the magnetic hysteresis, domain-wall displacement, and eddy current loss. The higher dielectric (epsilon'' = 23.5) and magnetic loss (micro'' = 0.22) contributes to the microwave absorption value of 22.5 dB (>99% attenuation) and are found to increase with the amount of ferrite constituents. The polymer was further characterized through Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). PMID- 20356301 TI - Complex hygrothermal effects on the glass transition of an epoxy-amine thermoset. AB - Anomalous hygrothermal behavior in an epoxy-amine thermoset was observed in terms of increases in glass-transition temperatures (T(g)) after immersion in water at different temperatures. Fourier transform near-infrared (FT-NIR) spectroscopic measurements showed that an increase in conversion was responsible for the increase in glass transition, while plasticization occurred simultaneously, rendering the hygrothermal behavior to be complex. To consider other factors affecting this complex hygrothermal behavior, a relationship between T(g) and conversion was constructed for the unexposed system and compared to the corresponding T(g) values for the exposed system at the same point of each conversion value. With this method, the conversion was successfully excluded to compare the T(g) values directly between the unexposed and exposed systems. This indicates the effects of other factors are negligible compared with the large plasticization effect. The plasticization effect was also evaluated quantitatively by observing T(g) differences between the unexposed and the exposed system as a function of absorbed water amount estimated by a characteristic water peak in the NIR spectra. The result indicates that there is additional anomalous behavior in which DeltaT(g) changes independently of the water amount at higher exposure temperatures. PMID- 20356302 TI - Liquid chromatographic determination of endogenous phytohormones in vegetable samples based on chemical derivatization with 6-oxy(acetylpiperazine) fluorescein. AB - In phytohormone analysis, mass spectrometry (MS)-based methods are primary and powerful tools. However, complex sample preparation and high cost are problems for their application. As a complement for MS-based methods, a new fluorescent labeling reagent for carboxylic acids, 6-oxy(acetylpiperazine) fluorescein (APF), has been used for the determination of endogenous phytohormones, including indolebutyric acid, 1-naphthaleneacetic acid and 2,4-dichlorophenoxyacetic acid. The derivatization yield was maximized by optimizing derivatization conditions in detail, and the derivatives of three phytohormones could be separated completely in 15 min on a C18 column with fluorescence detection at lambda(ex)/lambda(em) = 467/512 nm. The derivatization limits could reach 0.1 microM, and the detection limits (signal-to-noise ratio = 3) were 4.43-14.2 nM. The proposed method has been applied to the determination of the exogenous phytohormones in the crude extracts of vegetable samples without extra purification and enrichment with recoveries of 94.2-102.4%. PMID- 20356303 TI - Comparison of pasting and gel stabilities of waxy and normal starches from potato, maize, and rice with those of a novel waxy cassava starch under thermal, chemical, and mechanical stress. AB - Functional properties of normal and waxy starches from maize, rice, potato, and cassava as well as the modified waxy maize starch COLFLO 67 were compared. The main objective of this study is to position the recently discovered spontaneous mutation for amylose-free cassava starch in relation to the other starches with well-known characteristics. Paste clarity, wavelength of maximum absorption (lambda(max)), pasting properties, swelling power, solubility, and dispersed volume fraction measurements and gel stability (acid and alkaline resistance, shear, refrigeration, and freeze/thaw stability) were evaluated in the different types and sources of starch included in this study. lambda(max) in the waxy cassava starch was reduced considerably in comparison with that of normal cassava starch (535 vs 592 nm). RVA peak viscosity of waxy cassava starch was larger than in normal cassava starch (1119 vs 937 cP) and assumed a position intermediate between the waxy potato and maize starches. Acid, alkaline, and shear stability of waxy cassava starch were similar to normal cassava except for alkaline pH, at which it showed a low effect. Gels from normal root and tuber starches after refrigeration and freeze/thaw had lower syneresis than cereal starches. Gels from waxy starches (except for potato) did not present any syneresis after 5 weeks of storage at 4 degrees C. Waxy cassava starch was the only one not showing any syneresis after 5 weeks of storage at -20 degrees C. Natural waxy cassava starch is, therefore, a promising ingredient to formulate refrigerated or frozen food. PMID- 20356304 TI - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists: from bench to bedside. PMID- 20356305 TI - Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. PMID- 20356306 TI - Low-temperature pseudomorphic transformation of ordered hierarchical macro mesoporous SiO2/C nanocomposite to SiC via magnesiothermic reduction. AB - A magnesiothermic reduction synthesis approach is reported for direct conversion of SiO(2)/C composite nanostructures to corresponding SiC materials without losing their nanostructure morphologies. Crystalline SiC materials can be obtained by this approach at a temperature as low as 600 degrees C, only approximately half of that applied in the generally used carbothermal reduction and preceramic polymer pyrolysis methods. An ordered hierarchical macro mesoporous SiC material was synthesized for the first time as a demonstration. This pseudomorphic transformation can be regarded as a general synthesis method for different kinds of SiC nanostructures, and it can also be readily extended to other metal carbide materials as well as TiC. PMID- 20356307 TI - Fibrillar vs crystalline full-length beta-2-microglobulin studied by high resolution solid-state NMR spectroscopy. AB - Elucidating the fine structure of amyloid fibrils as well as understanding their processes of nucleation and growth remains a difficult yet essential challenge, directly linked to our current poor insight into protein misfolding and aggregation diseases. Here we consider beta-2-microglobulin (beta2m), the MHC-1 light chain component responsible for dialysis-related amyloidosis, which can give rise to amyloid fibrils in vitro under various experimental conditions, including low and neutral pH. We have used solid-state NMR to probe the structural features of fibrils formed by full-length beta2m (99 residues) at pH 2.5 and pH 7.4. A close comparison of 2D (13)C-(13)C and (15)N-(13)C correlation experiments performed on beta2m, in both the crystalline and fibrillar states, suggests that, in spite of structural changes affecting the protein loops linking the protein beta-strands, the protein chain retains a substantial share of its native secondary structure in the fibril assembly. Moreover, variations in the chemical shifts of the key Pro32 residue suggest the involvement of a cis-trans isomerization in the process of beta2m fibril formation. Lastly, the analogy of the spectra recorded on beta2m fibrils grown at different pH values hints at a conserved architecture of the amyloid species thus obtained. PMID- 20356308 TI - Dimeric quinidine-catalyzed enantioselective aminooxygenation of oxindoles: an organocatalytic approach to 3-hydroxyoxindole derivatives. AB - 3-Hydroxyoxindoles are common structural motifs found in a vast array of natural and biologically active molecules. Most catalytic methods for the asymmetric syntheses of these compounds require the use of transition-metal catalysts. In contrast, alternative catalytic procedures involving organocatalysis are scarce. Herein we disclose a novel aminooxygenation of oxindoles with nitrosobenzene catalyzed by a newly designed quinidine dimer to afford the desired products in good yields with enantioselectivities up to 96%. These reactions allow one to construct a C-O bond at the C(3) position of oxindoles with the creation of an oxygen-containing tetrasubstituted chiral center and provide a new, general organocatalytic approach to the synthesis of 3-hydroxyoxindole derivatives. PMID- 20356309 TI - Inducing alpha-helices in short oligopeptides through binding by an artificial hydrophobic cavity. AB - Short peptides were induced into alpha-helix conformations in water through enclathration to an artificial hydrophobic cavity. Peptides with two aromatic residues showed high affinity for the host, and these intermolecular aromatic aromatic interactions specifically drove the helical folding of short peptides. PMID- 20356310 TI - Visualization of polymer chain conformations in amorphous polyisocyanide Langmuir Blodgett films by atomic force microscopy. AB - Polymer Langmuir monolayers are an ideal model for two-dimensional (2D) polymer chains, but our understanding of them is still limited. Using atomic force microscopy, we have for the first time successfully visualized the polymer chain packings in amorphous polyisocyanide monolayers deposited on mica. The long polymer chains, which were partially forced to form hairpin-like conformations, were sophisticatedly packed in the 2D film without any chain stacking. The trend of the persistent lengths of the polymers in the 2D films fairly corresponded to those of 3D chains in solution. The molecular-level information provided by direct observations such as these will improve our understanding of polymers in 2D space. PMID- 20356311 TI - Lipid-protein nanodiscs as reference medium in detergent screening for high resolution NMR studies of integral membrane proteins. AB - The choice of a suitable detergent-based membrane mimetic is of crucial importance for high-resolution NMR studies of membrane proteins. The present report describes a new approach of detergent screening. It is based on the comparison of 2D (1)H,(15)N-correlation spectra of a protein in a membrane bilayer "reference" medium and in "trial" detergent-based environments. The proposed "reference" medium is the lipid-protein nanodisc (LPN) representing nanoscale phospholipid bilayers wrapped around by apolipoprotein A-1. The set of zwitterionic (DPC, DMPC/DHPC), anionic (SDS, LMPG, LPPG), and weakly cationic (LDAO) detergent-based media was screened for their ability to represent the native structure of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP. The VSD/LPN complexes composed of saturated zwitterionic (DMPC), anionic (DMPG), or a mixture of unsaturated differently charged (POPC/DOPG, 3:1) lipids were used as reference. All assayed detergent media demonstrate similar CD spectra of the domain with a high level (approximately 60%) of overall helicity but different 2D NMR spectra. Using the reference spectrum of the VSD in LPN, we were able to choose the detergent composition in which the membrane-like structure of the VSD is preserved. PMID- 20356312 TI - NMR structural and dynamical investigation of the isolated voltage-sensing domain of the potassium channel KvAP: implications for voltage gating. AB - The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP was studied by high-resolution NMR. The almost complete backbone resonance assignment and partial side-chain assignment of the (2)H,(13)C,(15)N-labeled VSD were obtained for the protein domain solubilized in DPC/LDAO (2:1) mixed micelles. Secondary and tertiary structures of the VSD were characterized using secondary chemical shifts and NOE contacts. These data indicate that the spatial structure of the VSD solubilized in micelles corresponds to the structure of the domain in an open state of the channel. NOE contacts and secondary chemical shifts of amide protons indicate the presence of tightly bound water molecule as well as hydrogen bond formation involving an interhelical salt bridge (Asp62-R133) that stabilizes the overall structure of the domain. The backbone dynamics of the VSD was studied using (15)N relaxation measurements. The loop regions S1-S2 and S2-S3 were found mobile, while the S3-S4 loop (voltage-sensor paddle) was found stable at the ps-ns time scale. The moieties of S1, S2, S3, and S4 helices sharing interhelical contacts (at the level of the Asp62-R133 salt bridge) were observed in conformational exchange on the micros-ms time scale. Similar exchange-induced broadening of characteristic resonances was observed for the VSD solubilized in the membrane of lipid-protein nanodiscs composed of DMPC, DMPG, and POPC/DOPG lipids. Apparently, the observed interhelical motions represent an inherent property of the VSD of the KvAP channel and can play an important role in the voltage gating. PMID- 20356313 TI - Toward flexibility-activity relationships by NMR spectroscopy: dynamics of Pin1 ligands. AB - Drug design involves iterative ligand modifications. For flexible ligands, these modifications often entail restricting conformational flexibility. However, defining optimal restriction strategies can be challenging if the relationship between ligand flexibility and biological activity is unclear. Here, we describe an approach for ligand flexibility-activity studies using Nuclear Magnetic Resonance (NMR) spin relaxation. Specifically, we use (13)C relaxation dispersion measurements to compare site-specific changes in ligand flexibility for a series of related ligands that bind a common macromolecular receptor. The flexibility changes reflect conformational reorganization resulting from formation of the receptor-ligand complex. We demonstrate this approach on three structurally similar but flexibly differentiated ligands of human Pin1, a peptidyl-prolyl isomerase. The approach is able to map the ligand dynamics relevant for activity and expose changes in those dynamics caused by conformational locking. Thus, NMR flexibility-activity studies can provide information to guide strategic ligand rigidification. As such, they help establish an experimental basis for developing flexibility-activity relationships (FAR) to complement traditional structure activity relationships (SAR) in molecular design. PMID- 20356314 TI - Electrophile affinity: quantifying reactivity for the bromination of arenes. AB - Electrophile affinity (Ealpha), a recently proposed theoretical construct based on computed energies of arenium ion formation, rationalizes the substrate reactivity and regioselectivity of S(E)Ar bromination of three sets of available experimental arene data where closely related conditions had been employed uniformly. The Ealpha parameters (computed at B3LYP/6-311+G(2d,2p)) correlated very well (r = 0.987) with the partial rate factors (log f) for 18 regiospecific brominations of benzene and various methyl benzenes. Analysis of the bromination reactivities of 32 mono- and polysubstituted benzenes including various polar groups gave similar results (r = 0.982). The electrophile affinity treatment also accounted satisfactorily (r = 0.957) for bromination reactivities of polybenzenoid hydrocarbons. Conversely, comparisons with NBO-based charges and the electrostatic potential at nuclei (EPN) were not generally successful. The uniform effectiveness of Ealpha treatments for the cases analyzed with regard both to relative substrate reactivity (e.g., benzene vs toluene) and to regiospecificity (e.g., the positional reactivity of toluene) supports the "limiting case" conventional interpretation of the electrophilic aromatic substitution mechanism as being governed by the energy of sigma-complex formation. Although other mechanisms are possible under different conditions, the computed energies of arene-dibromine pi-complex formation for the polysubstituted benzene set examined correlated poorly with experimental reactivity data (r = 0.714) and only varied from 1.8 (for benzene) to 3.5 kcal/mol, in contrast to the 10(12) range in reactivity measured experimentally. PMID- 20356315 TI - Medication errors in psychiatry: a comprehensive review. AB - Medication errors are among the most common medical errors and cause significant morbidity and in some cases mortality. The objective of this article is to review the literature on medication errors in psychiatry. We completed a comprehensive search of both peer- and non-peer-reviewed articles that investigated medication errors in psychiatry. Our primary focus was to examine patient-, provider- and system-related factors that contributed to medication errors. Due to differences in research design and denominators used to determine error rates, the reported prevalence rates of medication errors in psychiatry vary widely. Patient-related factors identified as contributing to medication errors included non-adherence to medication, failure of patients to inform their various care providers about the medications they are taking and symptoms of psychiatric illnesses. Provider related factors identified as contributing to medication errors were also identified and included clinical practices associated with prescribing, transcription, dispensing, administration and monitoring. Finally, the healthcare system also has a major role to play in reducing medication errors by ensuring seamless continuity of care, mandating medication reconciliation programmes, ensuring adequate clinical pharmacy services and supporting a nonpunitive medication error reporting system. Although the literature raises awareness of these specific contributing factors, there is still a great need for more systematic evaluations of the problem including root cause analysis. Medication errors in psychiatry have been studied almost exclusively in the inpatient setting and thus little is known about the incidence and significance in outpatient and community settings. PMID- 20356316 TI - Menopause Rating Scale as a screening tool in rural Turkey. AB - INTRODUCTION: Women living in rural areas of Turkey experience difficulties in accessing healthcare services, and this is attributed to distance from urban healthcare centers, financial barriers and poverty, a low education level, and gender discrimination. The purpose of this study was to test the applicability of the menopause rating scale (MRS) as a screening tool by primary healthcare professionals for identifying women with severe menopausal symptoms. The objectives of the study were to test the validity and reliability of the MRS in rural areas of Turkey, to determine estimation values for referral to the secondary level of healthcare, and to assess the prevalence of severe menopausal symptoms among rural Turkish women. METHODS: The sample size was 600 women. The Turkish version of the MRS and the Kupperman index were used to evaluate the severity of symptoms. The internal consistency coefficient (Cronbach's alpha) of the MRS was computed using the test-retest method. The influence of the MRS with regard to the decision to seek medical advice due to menopausal symptoms was considered the validity criterion, and the sensitivity and specificity of the test were established according to this criterion. Estimation values of the test were determined by ROC analysis. Independent variables for the severity of menopausal symptoms were determined using a logistic regression model. RESULTS: A positive correlation between the MRS and the Kupperman index was revealed (r=0.86, p=0.000). The estimation value or the MRS score that would predict whether a woman had visited a gynecologist at least once due to the severity of menopause symptoms was found to be 16, its sensitivity and specificity were both 60%. The MRS score was higher among participants who evaluated their general health as 'unfit' or who had advanced age, chronic disease, a history of dysmenorrhea, or who had had two or more miscarriages. CONCLUSIONS: This evaluation of the MRS indicates that the instrument is a comprehensible, useable, reliable screening test for the identification of women with severe menopausal symptoms. By screening using the MRS it is possible for primary healthcare workers in rural areas to identify women in need of referral to an upper-level healthcare institution. PMID- 20356317 TI - High body mass index in rural children. PMID- 20356319 TI - Proceedings of the VI National Congress of Pharmacology October 2009 - plenary lectures. PMID- 20356320 TI - Mapping of rice Ur1 (Undulated rachis-1) gene with effect on increasing spikelet number per panicle and sink size, and development of selection markers for the breeding by the use of Ur1. AB - Ur1 enhances secondary rachis-branching, resulting in more spikelets per panicle. This genic effect can increase grain yield by enlarging sink size. We conducted mapping of Ur1 using SSR markers, and detected markers usable for the MAS (marker assisted selection) for Ur1. Three Ur1 isogenic lines of recurrent parents Taichung 65, 'Shiokari' and 'Nishihikari'('T(U)', 'S(U)' and 'N(U)', respectively) were used. SSR-marker analysis indicated that each isogenic line had a non-substituted region containing Ur1 on chromosome 6 which was inherited from its donor parent. T(U) was crossed with a non-Ur1-carrying line, and the F(2) and F(3) populations were grown. Recombination values between the Ur1 locus and SSR-marker loci were obtained from data of the F(2) and F(3). On the basis of both the linkage relationship and the non-substituted regions in T(U), S(U) and N(U), candidate region of the Ur1 locus was narrowed to 0.139 Mb between the loci of up85938 and SSR17 on the long arm of chromosome 6. Genotypes of T(U) and other five Ur1-carrying lines at each locus of ten SSR markers near the Ur1 locus were determined, and allelic frequency at each locus was investigated for 27 japonica and 21 indica varieties. Consequently, SSR12 and SSR17 could be employed as MAS markers for Ur1. PMID- 20356322 TI - A conversation between Anton Bueschen and Darracott Vaughan. Interviewed by Darracott Vaughan. PMID- 20356323 TI - Benign prostatic hyperplasia: counting the cost of its management. PMID- 20356324 TI - The role of nocturia in the quality of life of men with lower urinary tract symptoms. PMID- 20356318 TI - Relationships between plasma membrane microdomains and HIV-1 assembly. AB - Advances in cell biology and biophysics revealed that cellular membranes consist of multiple microdomains with specific sets of components such as lipid rafts and TEMs (tetraspanin-enriched microdomains). An increasing number of enveloped viruses have been shown to utilize these microdomains during their assembly. Among them, association of HIV-1 (HIV type 1) and other retroviruses with lipid rafts and TEMs within the PM (plasma membrane) is well documented. In this review, I describe our current knowledge on interrelationships between PM microdomain organization and the HIV-1 particle assembly process. Microdomain association during virus particle assembly may also modulate subsequent virus spread. Potential roles played by microdomains will be discussed with regard to two post-assembly events, i.e., inhibition of virus release by a raft-associated protein BST-2/tetherin and cell-to-cell HIV-1 transmission at virological synapses. PMID- 20356326 TI - The primary care physician as an advocate for the pharmaceutical industry. PMID- 20356328 TI - Surgery illustrated - surgical atlas ileal neobladder. PMID- 20356330 TI - Introduction to a Virtual Special Issue on mycoheterotrophy: New Phytologist sheds light on non-green plants. PMID- 20356331 TI - A novel lipid signal in the arbuscular mycorrhizal symbiosis within eyesight? PMID- 20356332 TI - Changing juvenile growth patterns in tropical trees: selective effects, history, or both? PMID- 20356333 TI - Fungal hosts for mycoheterotrophic plants: a nonexclusive, but highly selective club. PMID- 20356334 TI - Physiological ecology of mycoheterotrophy. PMID- 20356335 TI - Evolution of mycoheterotrophy in plants: a phylogenetic perspective. PMID- 20356337 TI - Can water droplets on leaves cause leaf scorch? PMID- 20356338 TI - Dandelions 'remember' stress: heritable stress-induced methylation patterns in asexual dandelions. PMID- 20356339 TI - Ethylene--a key arbitrator to plant-fungal symbiotic interactions? PMID- 20356340 TI - Advancing our current understanding of plant-fungal symbioses: bridging scales from local to global. PMID- 20356341 TI - Interwoven branches of the plant and fungal trees of life. PMID- 20356342 TI - Not every fungus is everywhere: scaling to the biogeography of fungal-plant interactions across roots, shoots and ecosystems. PMID- 20356343 TI - Moving from pattern to process in fungal symbioses: linking functional traits, community ecology and phylogenetics. PMID- 20356344 TI - The Sphagnum air-gun mechanism resurrected. PMID- 20356336 TI - Nomenclature for factors of the HLA system, 2010. PMID- 20356346 TI - Phosphatidic acid formation is required for extracellular ATP-mediated nitric oxide production in suspension-cultured tomato cells. AB - *In animals and plants, extracellular ATP exerts its effects by regulating the second messengers Ca(2+), nitric oxide (NO) and reactive oxygen species (ROS). In animals, phospholipid-derived molecules, such as diacylglycerol, phosphatidic acid (PA) and inositol phosphates, have been associated with the extracellular ATP signaling pathway. The involvement of phospholipids in extracellular ATP signaling in plants, as it is established in animals, is unknown. *In vivo phospholipid signaling upon extracellular ATP treatment was studied in (32)P(i) labeled suspension-cultured tomato (Solanum lycopersicum) cells. *Here, we report that, in suspension-cultured tomato cells, extracellular ATP induces the formation of the signaling lipid phosphatidic acid. Exogenous ATP at doses of 0.1 and 1 mM induce the formation of phosphatidic acid within minutes. Studies on the enzymatic sources of phosphatidic acid revealed the participation of both phospholipase D and C in concerted action with diacylglycerol kinase. *Our results suggest that extracellular ATP-mediated nitric oxide production is downstream of phospholipase C/diacylglycerol kinase activation. PMID- 20356347 TI - Underground friends or enemies: model plants help to unravel direct and indirect effects of arbuscular mycorrhizal fungi on plant competition. AB - *We studied the effects of two arbuscular mycorrhizal (AM) fungi, singly or together, on the outcome of competition between a host (tomato cultivar, wild type (WT)) and a surrogate nonhost (rmc, a mycorrhiza-defective mutant of WT) as influenced by the contributions of the direct and AM phosphorus (P) uptake pathways to plant P. *We grew plants singly or in pairs of the same or different genotypes (inoculated or not) in pots containing a small compartment with (32)P labelled soil accessible to AM fungal hyphae and determined expression of orthophosphate (P(i)) transporter genes involved in both AM and direct P uptake. *Gigaspora margarita increased WT competitive effects on rmc. WT and rmc inoculated with Glomus intraradices both showed growth depressions, which were mitigated when G. margarita was present. Orthophosphate transporter gene expression and (32)P transfer showed that the AM pathway operated in single inoculated WT, but not in rmc. *Effects of AM fungi on plant competition depended on the relative contributions of AM and direct pathways of P uptake. Glomus intraradices reduced the efficiency of direct uptake in both WT and rmc. The two fungus combination showed that interactions between fungi are important in determining outcomes of plant competition. PMID- 20356349 TI - The United States of America and the Islamic Republic of Iran: the path to preventing traffic injuries? PMID- 20356350 TI - The burden of injuries in Iranian children in 2005. AB - BACKGROUND: Child injury is recognized as a global health problem. Injuries caused the highest burden of disease among the total population of Iran in 2003. We aimed to estimate the morbidity, mortality, and disease burden caused by child injuries in the 0- to 14-year-old population of Iran in 2005. METHODS: We estimated average age- and sex-specific mortality rates for different types of child injuries from 2001 to 2006 using Iran's death registration data. Incidence rates for nonfatal outcomes of child injuries in 2005 were estimated through a time- and place-limited sample hospital registry study for injuries. We used the World Health Organization's methods for estimation of years of life lost due to premature mortality and years lived with disability in 2005. RESULTS: Injuries were the most important cause of death in children ages 1 to 14, with 35, 33.4, 24.9, and 22.9 deaths per 100,000 in the 0-14, 1-4, 5-9, and 10-14 age groups respectively. Road transport injuries were responsible for the highest death rate per 100,000 population among all types of injuries in children, with 15.5 for ages 0-14, 16.1 for ages 1-4, 16.3 for ages 5-9, and 13.1 for ages 10-14. Incidence rates of injuries leading to hospitalization were 459, 530, and 439 per 100,000 in the 0-14, 1-4, and 5-14 age groups respectively. Incidence rates of injuries leading to outpatient care were 1,812, 2,390, and 1,650 per 100,000 in the same age groups respectively. Among injury types, falls and burns had the highest hospitalization and outpatient care incidence rates. CONCLUSIONS: Injuries, particularly road transport injuries, were the most important health problem of children in Iran in 2003 and 2005. Strong social policy is needed to ensure child survival. PMID- 20356351 TI - Patient safety culture lives in departments and wards: multilevel partitioning of variance in patient safety culture. AB - BACKGROUND: Aim of study was to document 1) that patient safety culture scores vary considerably by hospital department and ward, and 2) that much of the variation is across the lowest level organizational units: the wards. Setting of study: 500-bed Norwegian university hospital, September-December 2006. METHODS: Data collected from 1400 staff by (the Norwegian version of) the generic version of the Safety Attitudes Questionnaire (SAQ Short Form 2006). Multilevel analysis by MLwiN version 1.10. RESULTS: Considerable parts of the score variations were at the ward and department levels. More organization level variation was seen at the ward level than at the department level. CONCLUSIONS: Patient safety culture improvement efforts should not be limited to all-hospital interventions or interventions aimed at entire departments, but include involvement at the ward level, selectively aimed at low-scoring wards. Patient safety culture should be studied as closely to the patient as possible. There may be such a thing as "hospital safety culture" and the variance across hospital departments indicates the existence of department safety cultures. However, neglecting the study of patient safety culture at the ward level will mask important local variations. Safety culture research and improvement should not stop at the lowest formal level of the hospital (wards, out-patient clinics, ERs), but proceed to collect and analyze data on the micro-units within them. PMID- 20356352 TI - Transcriptome response to pollutants and insecticides in the dengue vector Aedes aegypti using next-generation sequencing technology. AB - BACKGROUND: The control of mosquitoes transmitting infectious diseases relies mainly on the use of chemical insecticides. However, mosquito control programs are now threatened by the emergence of insecticide resistance. Hitherto, most research efforts have been focused on elucidating the molecular basis of inherited resistance. Less attention has been paid to the short-term response of mosquitoes to insecticides and pollutants which could have a significant impact on insecticide efficacy. Here, a combination of LongSAGE and Solexa sequencing was used to perform a deep transcriptome analysis of larvae of the dengue vector Aedes aegypti exposed for 48 h to sub-lethal doses of three chemical insecticides and three anthropogenic pollutants. RESULTS: Thirty millions 20 bp cDNA tags were sequenced, mapped to the mosquito genome and clustered, representing 6850 known genes and 4868 additional clusters not located within predicted genes. Mosquitoes exposed to insecticides or anthropogenic pollutants showed considerable modifications of their transcriptome. Genes encoding cuticular proteins, transporters, and enzymes involved in the mitochondrial respiratory chain and detoxification processes were particularly affected. Genes and molecular mechanisms potentially involved in xenobiotic response and insecticide tolerance were identified. CONCLUSIONS: The method used in the present study appears as a powerful approach for investigating fine transcriptome variations in genome sequenced organisms and can provide useful informations for the detection of novel transcripts. At the biological level, despite low concentrations and no apparent phenotypic effects, the significant impact of these xenobiotics on mosquito transcriptomes raise important questions about the 'hidden impact' of anthropogenic pollutants on ecosystems and consequences on vector control. PMID- 20356353 TI - Low HIV testing rates among tuberculosis patients in Kampala, Uganda. AB - BACKGROUND: HIV testing among tuberculosis patients is critical in improving morbidity and mortality as those found to be HIV positive will be offered a continuum of care including ART if indicated. We conducted a cross-sectional study in three Kampala City primary care clinics: to assess the level of HIV test uptake among newly diagnosed pulmonary tuberculosis (PTB) patients; to assess patient and health worker factors associated with HIV test uptake; and to determine factors associated with HIV test uptake at the primary care clinics METHODS: Adult patients who had been diagnosed with smear-positive PTB at a primary care clinic or at the referral hospital and who were being treated at any of the three clinics were interviewed. Associations between having taken the test as the main outcome and explanatory variables were assessed by multivariate logistic regression. RESULTS: Between April and October 2007, 112 adults were included in the study. An HIV test had been offered to 74 (66%). Of the 112 patients, 61 (82%) had accepted the test; 45 (74%) had eventually been tested; and 32 (29%) had received their test results.Patients who were <25 yeas old, female or unemployed, or had reported no previous HIV testing, were more likely to have been tested. The strongest predictor of having been tested was if patients had been diagnosed at the referral hospital compared to the city clinic (adjusted OR 24.2; 95% CI 6.7-87.7; p < 0.001). This primarily reflected an "opt out" (uptake 94%) versus an "opt-in" (uptake 53%) testing policy. CONCLUSIONS: The overall HIV test uptake was surprisingly low at 40%. The HIV test uptake was significantly higher among TB patients who were identified at hospital, among females and in the unemployed. PMID- 20356354 TI - Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila. AB - BACKGROUND: Speculation regarding the importance of changes in gene regulation in determining major phylogenetic patterns continues to accrue, despite a lack of broad-scale comparative studies examining how patterns of gene expression vary during development. Comparative transcriptional profiling of adult interspecific hybrids and their parental species has uncovered widespread divergence of the mechanisms controlling gene regulation, revealing incompatibilities that are masked in comparisons between the pure species. However, this has prompted the suggestion that misexpression in adult hybrids results from the downstream cascading effects of a subset of genes improperly regulated in early development. RESULTS: We sought to determine how gene expression diverges over development, as well as test the cascade hypothesis, by profiling expression in males of Drosophila melanogaster, D. sechellia, and D. simulans, as well as the D. simulans (female) x D. sechellia (male) male F1 hybrids, at four different developmental time points (3rd instar larval, early pupal, late pupal, and newly emerged adult). Contrary to the cascade model of misexpression, we find that there is considerable stage-specific autonomy of regulatory breakdown in hybrids, with the larval and adult stages showing significantly more hybrid misexpression as compared to the pupal stage. However, comparisons between pure species indicate that genes expressed during earlier stages of development tend to be more conserved in terms of their level of expression than those expressed during later stages, suggesting that while Von Baer's famous law applies at both the level of nucleotide sequence and expression, it may not apply necessarily to the underlying overall regulatory network, which appears to diverge over the course of ontogeny and which can only be ascertained by combining divergent genomes in species hybrids. CONCLUSION: Our results suggest that complex integration of regulatory circuits during morphogenesis may lead to it being more refractory to divergence of underlying gene regulatory mechanisms--more than that suggested by the conservation of gene expression levels between species during earlier stages. This provides support for a 'developmental hourglass' model of divergence of gene expression in Drosophila resulting in a highly conserved pupal stage. PMID- 20356355 TI - Time-trends in the utilization of decentralized mental health services in Norway A natural experiment: The VELO-project. AB - BACKGROUND: There are few reports on the effects of extensive decentralization of mental health services. We investigated the total patterns of utilization in a local-bed model and a central-bed model. METHODS: In a time-trend case-registry design, 7635 single treatment episodes, from the specialist and municipality services in 2003-2006, were linked to 2975 individual patients over all administrative levels. Patterns of utilization were analyzed by univariate comparisons and multivariate regressions. RESULTS: Total treated prevalence was consistently higher for the central-bed system. Outpatient utilization increased markedly, in the central-bed system. Utilization of psychiatric beds decreased, only in the central-bed system. Utilization of highly supported municipality units increased in both systems. Total utilization of all types of services, showed an additive pattern in the local-bed system and a substitutional pattern in the central-bed system. Only severe diagnoses predicted inpatient admission in the central-bed system, whereas also anxiety-disorders and outpatient consultations predicted inpatient admission in the local-bed system. Characteristics of the inpatient populations changed markedly over time, in the local-bed system. CONCLUSIONS: Geographical availability is not important as a filter in patients' pathway to inpatient care, and the association between distance to hospital and utilization of psychiatric beds may be an historical artefact. Under a public health-insurance system, local psychiatric personnel as gatekeepers for inpatient care may be of greater importance than the availability of local psychiatric beds. Specialist psychiatric beds and highly supported municipality units for people with mental health problems do not work together in terms of utilization. Outpatient and day-hospital services may be filters in the pathway to inpatient care, however this depends on the structure of the whole service-system. Local integration of psychiatric services may bring about additive, rather than substitutional patterns of total utilization. A large proportion of decentralized psychiatric beds may hinder the development of various local psychiatric services, with negative consequences for overall treated prevalence. PMID- 20356356 TI - When to start antiretroviral therapy in resource-limited settings: a human rights analysis. AB - BACKGROUND: Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration. DISCUSSION: According to our analysis, a policy of earlier ART initiation would better serve both public health and human rights objectives. We highlight a number of policy approaches that could be taken to help meet this aim, including increased international financial support, alternative models of care, and policies to secure the most affordable sources of appropriate antiretroviral drugs. SUMMARY: Widespread implementation of earlier ART initiation is challenging in resource-limited settings. Nevertheless, rationing of essential medicines is a restriction of human rights, and the principle of least restriction serves to focus attention on alternative measures such as adapting health service models to increase capacity, decreasing costs, and seeking additional international funding. Progressive realisation using well defined steps will be necessary to allow for a phased implementation as part of a framework of short-term targets towards nationwide policy adoption, and will require international technical and financial support. PMID- 20356357 TI - Report on the 1st scientific meeting of the "Verein zur Forderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009. AB - Report on the 1st scientific meeting of the "Verein zur Forderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Mittenwalde/Motzen, Germany, Oct. 30th - Nov. 1st, 2009. A scientific meeting report. PMID- 20356358 TI - Assessing the structural conservation of protein pockets to study functional and allosteric sites: implications for drug discovery. AB - BACKGROUND: With the classical, active-site oriented drug-development approach reaching its limits, protein ligand-binding sites in general and allosteric sites in particular are increasingly attracting the interest of medicinal chemists in the search for new types of targets and strategies to drug development. Given that allostery represents one of the most common and powerful means to regulate protein function, the traditional drug discovery approach of targeting active sites can be extended by targeting allosteric or regulatory protein pockets that may allow the discovery of not only novel drug-like inhibitors, but activators as well. The wealth of available protein structural data can be exploited to further increase our understanding of allosterism, which in turn may have therapeutic applications. A first step in this direction is to identify and characterize putative effector sites that may be present in already available structural data. RESULTS: We performed a large-scale study of protein cavities as potential allosteric and functional sites, by integrating publicly available information on protein sequences, structures and active sites for more than a thousand protein families. By identifying common pockets across different structures of the same protein family we developed a method to measure the pocket's structural conservation. The method was first parameterized using known active sites. We characterized the predicted pockets in terms of sequence and structural conservation, backbone flexibility and electrostatic potential. Although these different measures do not tend to correlate, their combination is useful in selecting functional and regulatory sites, as a detailed analysis of a handful of protein families shows. We finally estimated the numbers of potential allosteric or regulatory pockets that may be present in the data set, finding that pockets with putative functional and effector characteristics are widespread across protein families. CONCLUSIONS: Our results show that structurally conserved pockets are a common feature of protein families. The structural conservation of protein pockets, combined with other characteristics, can be exploited in drug discovery procedures, in particular for the selection of the most appropriate target protein and pocket for the design of drugs against entire protein families or subfamilies (e.g. for the development of broad-spectrum antimicrobials) or against a specific protein (e.g. in attempting to reduce side effects). PMID- 20356359 TI - ISS mapped from ICD-9-CM by a novel freeware versus traditional coding: a comparative study. AB - BACKGROUND: Injury severity measures are based either on the Abbreviated Injury Scale (AIS) or the International Classification of diseases (ICD). The latter is more convenient because routinely collected by clinicians for administrative reasons. To exploit this advantage, a proprietary program that maps ICD-9-CM into AIS codes has been used for many years. Recently, a program called ICDPIC trauma and developed in the USA has become available free of charge for registered STATA users. We compared the ICDPIC calculated Injury Severity Score (ISS) with the one from direct, prospective AIS coding by expert trauma registrars (dAIS). METHODS: The administrative records of the 289 major trauma cases admitted to the hospital of Udine-Italy from 1 July 2004 to 30 June 2005 and enrolled in the Italian Trauma Registry were retrieved and ICDPIC-ISS was calculated. The agreement between ICDPIC-ISS and dAIS-ISS was assessed by Cohen's Kappa and Bland-Altman charts. We then plotted the differences between the 2 scores against the ratio between the number of traumatic ICD-9-CM codes and the number of dAIS codes for each patient (DIARATIO). We also compared the absolute differences in ISS among 3 groups identified by DIARATIO. The discriminative power for survival of both scores was finally calculated by ROC curves. RESULTS: The scores matched in 33/272 patients (12.1%, k 0.07) and, when categorized, in 80/272 (22.4%, k 0.09). The Bland-Altman average difference was 6.36 (limits: minus 22.0 to plus 34.7). ICDPIC-ISS of 75 was particularly unreliable. The differences increased (p < 0.01) as DIARATIO increased indicating incomplete administrative coding as a cause of the differences. The area under the curve of ICDPIC-ISS was lower (0.63 vs. 0.76, p = 0.02). CONCLUSIONS: Despite its great potential convenience, ICPIC ISS agreed poorly with its conventionally calculated counterpart. Its discriminative power for survival was also significantly lower. Incomplete ICD-9 CM coding was a main cause of these findings. Because this quality of coding is standard in Italy and probably in other European countries, its effects on the performances of other trauma scores based on ICD administrative data deserve further research. Mapping ICD-9-CM code 862.8 to AIS of 6 is an overestimation. PMID- 20356360 TI - EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression--a case report. AB - Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD.We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD. PMID- 20356361 TI - Evaluation of the hyplex TBC PCR test for detection of Mycobacterium tuberculosis complex in clinical samples. AB - BACKGROUND: Tuberculosis (TB) is one of the major public health concerns worldwide. The detection of the pathogen Mycobacterium tuberculosis complex (MTBC) as early as possible has a great impact on the effective control of the spread of the disease. In our study, we evaluated the hyplex TBC PCR test (BAG Health Care GmbH), a novel assay using a nucleic acid amplification technique (NAAT) with reverse hybridisation and ELISA read out for the rapid detection of M. tuberculosis directly in clinical samples. RESULTS: A total of 581 respiratory and non-respiratory specimens from our pneumological hospital and the National TB Institute of Uzbekistan were used for the evaluation of the PCR assay. Of these, 292 were classified as TB samples and 289 as non-TB samples based on the results of the TB cultures as reference method. The PCR results were initially used to optimise the cut-off value of the hyplex TBC test system by means of a ROC analysis. The overall sensitivity of the assay was determined to be 83.1%. In smear-positive TB samples, the sensitivity of the hyplex TBC PCR test was estimated to 93.4% versus 45.1% in smear-negative samples. The specificity of the test was 99.25%. Of the two specimens (0.75%) with false-positive PCR results, one yielded a culture positive for non-tuberculous mycobacteria. Based on the assumption of a prevalence of 8% TB positives among the samples in our diagnostic TB laboratory, the positive and negative predictive values were estimated to 90.4% and 98.5%, respectively. CONCLUSIONS: The hyplex TBC PCR test is an accurate NAAT assay for a rapid and reliable detection of M. tuberculosis in various respiratory and non-respiratory specimens. Compared to many other conventional NAAT assays, the hyplex TBC PCR test is in a low price segment which makes it an attractive option for developing and emerging countries with high TB burdens. PMID- 20356362 TI - Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis. AB - INTRODUCTION: Matrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality. METHODS: Forty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months. RESULTS: The levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal. CONCLUSIONS: MMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels in skin blister and serum were associated with more severe organ dysfunctions. PMID- 20356363 TI - A systematic review of task- shifting for HIV treatment and care in Africa. AB - BACKGROUND: Shortages of human resources for health (HRH) have severely hampered the rollout of antiretroviral therapy (ART) in sub-Saharan Africa. Current rollout models are hospital- and physician-intensive. Task shifting, or delegating tasks performed by physicians to staff with lower-level qualifications, is considered a means of expanding rollout in resource-poor or HRH-limited settings. METHODS: We conducted a systematic literature review. Medline, the Cochrane library, the Social Science Citation Index, and the South African National Health Research Database were searched with the following terms: task shift*, balance of care, non-physician clinicians, substitute health care worker, community care givers, primary healthcare teams, cadres, and nurs* HIV. We mined bibliographies and corresponded with authors for further results. Grey literature was searched online, and conference proceedings searched for abstracts. RESULTS: We found 2960 articles, of which 84 were included in the core review. 51 reported outcomes, including research from 10 countries in sub-Saharan Africa. The most common intervention studied was the delegation of tasks (especially initiating and monitoring HAART) from doctors to nurses and other non physician clinicians. Five studies showed increased access to HAART through expanded clinical capacity; two concluded task shifting is cost effective; 9 showed staff equal or better quality of care; studies on non-physician clinician agreement with physician decisions was mixed, with the majority showing good agreement. CONCLUSIONS: Task shifting is an effective strategy for addressing shortages of HRH in HIV treatment and care. Task shifting offers high-quality, cost-effective care to more patients than a physician-centered model. The main challenges to implementation include adequate and sustainable training, support and pay for staff in new roles, the integration of new members into healthcare teams, and the compliance of regulatory bodies. Task shifting should be considered for careful implementation where HRH shortages threaten rollout programmes. PMID- 20356364 TI - Primary adenomyoepithelioma of tonsil. AB - We present a case of adenomyoepithlioma (AME) arising from the tonsil. AME is an uncommon tumor that typically arises in breast, but rarely found in salivary glands, lung, and skin. Its biological features have not been thoroughly characterized. Here we describe a primary AME originating from the tonsil. The pathologic changes were characterized by hypercellularity, the dominance of both epithelial and myoepithelial cells. Malignancy was evidenced by the presence of a high mitotic rate and invasive growth. The epithelial cells express high levels of cytokeratin and epithelial membrane antigen (EMA). The myoepithelial cells show positive staining for calponin, p63, vimentin, and S-100. A thorough review of the literature indicates that this is likely the first reported case of AME from the tonsil. Following descriptions of the diagnosis, treatment, and prognosis of this specific case, pathologic and clinical characteristics of AME from other tissues are also compiled and discussed. PMID- 20356365 TI - Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. AB - INTRODUCTION: The pathophysiology of sepsis-associated encephalopathy (SAE) is not entirely clear. One of the possible underlying mechanisms is the alteration of the cerebral microvascular function induced by the systemic inflammation. The aim of the present work was to test whether cerebral vasomotor-reactivity is impaired in patients with SAE. METHODS: Patients fulfilling the criteria of clinical sepsis and showing disturbance of consciousness of any severity were included (n = 14). Non-septic persons without previous diseases affecting cerebral vasoreactivity served as controls (n = 20). Transcranial Doppler blood flow velocities were measured at rest and at 5, 10, 15 and 20 minutes after intravenous administration of 15 mg/kgBW acetazolamide. The time course of the acetazolamide effect on cerebral blood flow velocity (cerebrovascular reactivity, CVR) and the maximal vasodilatory effect of acetazolemide (cerebrovascular reserve capacity, CRC) were compared among the groups. RESULTS: Absolute blood flow velocities after administration of the vasodilator drug were higher among control subjects than in SAE. Assessment of the time-course of the vasomotor reaction showed that patients with SAE reacted slower to the vasodilatory stimulus than control persons. When assessing the maximal vasodilatory ability of the cerebral arterioles to acetazolamide during vasomotor testing, we found that patients with SAE reacted to a lesser extent to the drug than did control subjects (CRC controls:46.2 +/- 15.9%, CRC SAE: 31,5 +/- 15.8%, P < 0.01). CONCLUSIONS: We conclude that cerebrovascular reactivity is impaired in patients with SAE. The clinical significance of this pathophysiological finding has to be assessed in further studies. PMID- 20356366 TI - DNA microarray analysis of Salmonella serotype Typhimurium strains causing different symptoms of disease. AB - BACKGROUND: Salmonella enterica subsp. enterica is one of the leading food-borne pathogens in the USA and European countries. Outcome of human Salmonella serotype Typhimurium infections ranges from mild self-limiting diarrhoea to severe diarrhoea that requires hospitalization. Increased knowledge of the mechanisms that are responsible for causing infection and especially the severity of infection is of high interest. RESULTS: Strains were selected from patients with mild infections (n = 9) and patients with severe infections (n = 9) and clinical data allowed us to correct for known underlying diseases. Additionally, outbreak isolates (n = 3) were selected. Strains were analyzed on a DNA-DNA microarray for presence or absence of 281 genes covering marker groups of genes related to pathogenicity, phages, antimicrobial resistance, fimbriae, mobility, serotype and metabolism. Strains showed highly similar profiles when comparing virulence associated genes, but differences between strains were detected in the prophage marker group. The Salmonella virulence plasmid was present in 72% of the strains, but presence or absence of the virulence plasmid did not correspond to disease symptoms. A dendrogram clustered strains into four groups. Clustering confirmed DT104 as being a clonal phagetype. Clustering of the remaining strains was mainly correlated to presence or absence of the virulence plasmid and mobile elements such as transposons. Each of the four clusters in the tree represented an almost equal amount of strains causing severe or mild symptoms of infection. CONCLUSIONS: We investigated clinical significance of known virulence factors of Salmonella serotype Typhimurium strains causing different disease symptoms, and conclude that the few detected differences in Salmonella serotype Typhimurium do not affect outcome of human disease. PMID- 20356367 TI - Comparative analysis of right element mutant lox sites on recombination efficiency in embryonic stem cells. AB - BACKGROUND: Cre-mediated site-specific integrative recombination in mouse embryonic stem (ES) cells is a useful tool for genome engineering, allowing precise and repeated site-specific integration. To promote the integrative reaction, a left element/right element (LE/RE) mutant strategy using a pair of lox sites with mutations in the LE or RE of the lox sequence has previously been developed. Recombination between LE and RE mutant lox produces a wild-type loxP site as well as an LE+RE double mutant lox site, which has mutations in both sides and less affinity to Cre, resulting in stable integration. We previously demonstrated successful integrative recombination using lox71 (an LE mutant) and lox66 (an RE mutant) in ES cells. Recently, other LE/RE mutant lox sites showing higher recombination efficiency in Escherichia coli have been reported. However, their recombination efficiency in mammalian cells remains to be analyzed. RESULTS: Using ES cells, we compared six RE mutant lox sites, focusing on their recombination efficiency with lox71. All of the RE mutant lox sites showed similar recombination efficiency. We then analyzed the stability of the recombined product, i.e., the LE+RE double mutant lox site, under continuous and strong Cre activity in ES cells. Two RE mutants, loxJTZ17 and loxKR3, produced more stable LE+RE double mutant lox than did the lox66/71 double mutant. CONCLUSION: The two mutant RE lox sites, loxJTZ17 and loxKR3, are more suitable than lox66 for Cre-mediated integration or inversion in ES cells. PMID- 20356369 TI - Testing the sensitivity and specificity of the fluorescence microscope (Cyscope) for malaria diagnosis. AB - BACKGROUND: Early diagnosis and treatment of malaria are necessary components in the control of malaria. The gold standard light microscopy technique has high sensitivity, but is a relatively time-consuming procedure especially during epidemics and in areas of high endemicity. This study attempted to test the sensitivity and specificity of a new diagnostic tool - the Cyscope fluorescence microscope, which is based on the use of Plasmodium nucleic acid-specific fluorescent dyes to facilitate detection of the parasites even in low parasitaemia conditions due to the contrast with the background. METHODS: In this study, 293 febrile patients above the age of 18 years attending the malaria treatment centre in Sinnar State (Sudan) were interviewed using a structured questionnaire. Finger-prick blood samples were also collected from the participants to be tested for malaria using the hospital's microscope, the reference laboratory microscope, as well as the Cyscope microscope. The results of the investigations were then used to calculate the sensitivity, specificity, and positive and negative predictive values of the Cyscope microscope in reference to gold standard light microscopy. RESULTS: The sensitivity was found to be 98.2% (95% CI: 90.6%-100%); specificity = 98.3% (95% CI: 95.7% - 99.5%); positive predictive value = 93.3% (95% CI: 83.8% - 98.2%); and negative predictive value = 99.6% (95% CI: 97.6% - 100%). CONCLUSIONS: In conclusion, the Cyscope microscope was found to be sensitive, specific and provide rapid, reliable results in a matter of less than 10 minutes. The Cyscope microscope should be considered as a viable, cheaper and time-saving option for malaria diagnosis, especially in areas where Plasmodium falciparum is the predominant parasite. PMID- 20356368 TI - Helicobacter pylori: a poor man's gut pathogen? AB - Helicobacter pylori is one of the human pathogens with highest prevalence around the world; yet, its principal mode of transmission remains largely unknown. The role of H. pylori in gastric disease and cancer has not been established until the end of the 20th century. Since then, its epidemiology has been extensively studied, and an accruing body of literature suggests that not all humans are equally at risk of infection by this gut pathogen. Here, we briefly review the different epidemiological aspects of H. pylori infection with emphasis on those factors related to human poverty. The epidemiology of H. pylori infection is characterized by marked differences between developing and developed countries, notably among children. In addition, congruent lines of evidence point out to socioeconomic factors and living standards as main determinants of the age dependent acquisition rate of H. pylori, and consequently its prevalence. These data are alarming in the light of the changing global climate and birth rate, which are expected to change the demography of our planet, putting more children at risk of H. pylori and its complications for years to come. PMID- 20356370 TI - Phylogeny and expression of carbonic anhydrase-related proteins. AB - BACKGROUND: Carbonic anhydrases (CAs) are found in many organisms, in which they contribute to several important biological processes. The vertebrate alpha-CA family consists of 16 subfamilies, three of which (VIII, X and XI) consist of acatalytic proteins. These are named carbonic anhydrase related proteins (CARPs), and their inactivity is due to absence of one or more Zn-binding histidine residues. In this study, we analyzed and evaluated the distribution of genes encoding CARPs in different organisms using bioinformatic methods, and studied their expression in mouse tissues using immunohistochemistry and real-time quantitative PCR. RESULTS: We collected 84 sequences, of which 22 came from novel or improved gene models which we created from genome data. The distribution of CARP VIII covers vertebrates and deuterostomes, and CARP X appears to be universal in the animal kingdom. CA10-like genes have had a separate history of duplications in the tetrapod and fish lineages. Our phylogenetic analysis showed that duplication of CA10 into CA11 has occurred only in tetrapods (found in mammals, frogs, and lizards), whereas an independent duplication of CA10 was found in fishes. We suggest the name CA10b for the second fish isoform. Immunohistochemical analysis showed a high expression level of CARP VIII in the mouse cerebellum, cerebrum, and also moderate expression in the lung, liver, salivary gland, and stomach. These results also demonstrated low expression in the colon, kidney, and Langerhans islets. CARP X was moderately expressed in the cerebral capillaries and the lung and very weakly in the stomach and heart. Positive signals for CARP XI were observed in the cerebellum, cerebrum, liver, stomach, small intestine, colon, kidney, and testis. In addition, the results of real-time quantitative PCR confirmed a wide distribution for the Car8 and Car11 mRNAs, whereas the expression of the Car10 mRNA was restricted to the frontal cortex, parietal cortex, cerebellum, midbrain, and eye. CONCLUSIONS: CARP sequences have been strongly conserved between different species, and all three CARPs show high expression in the mouse brain and CARP VIII is also expressed in several other tissues. These findings suggest an important functional role for these proteins in mammals. PMID- 20356371 TI - An integrated machine learning approach for predicting DosR-regulated genes in Mycobacterium tuberculosis. AB - BACKGROUND: DosR is an important regulator of the response to stress such as limited oxygen availability in Mycobacterium tuberculosis. Time course gene expression data enable us to dissect this response on the gene regulatory level. The mRNA expression profile of a regulator, however, is not necessarily a direct reflection of its activity. Knowing the transcription factor activity (TFA) can be exploited to predict novel target genes regulated by the same transcription factor. Various approaches have been proposed to reconstruct TFAs from gene expression data. Most of them capture only a first-order approximation to the complex transcriptional processes by assuming linear gene responses and linear dynamics in TFA, or ignore the temporal information in data from such systems. RESULTS: In this paper, we approach the problem of inferring dynamic hidden TFAs using Gaussian processes (GP). We are able to model dynamic TFAs and to account for both linear and nonlinear gene responses. To test the validity of the proposed approach, we reconstruct the hidden TFA of p53, a tumour suppressor activated by DNA damage, using published time course gene expression data. Our reconstructed TFA is closer to the experimentally determined profile of p53 concentration than that from the original study. We then apply the model to time course gene expression data obtained from chemostat cultures of M. tuberculosis under reduced oxygen availability. After estimation of the TFA of DosR based on a number of known target genes using the GP model, we predict novel DosR-regulated genes: the parameters of the model are interpreted as relevance parameters indicating an existing functional relationship between TFA and gene expression. We further improve the prediction by integrating promoter sequence information in a logistic regression model. Apart from the documented DosR-regulated genes, our prediction yields ten novel genes under direct control of DosR. CONCLUSIONS: Chemostat cultures are an ideal experimental system for controlling noise and variability when monitoring the response of bacterial organisms such as M. tuberculosis to finely controlled changes in culture conditions and available metabolites. Nonlinear hidden TFA dynamics of regulators can be reconstructed remarkably well with Gaussian processes from such data. Moreover, estimated parameters of the GP can be used to assess whether a gene is controlled by the reconstructed TFA or not. It is straightforward to combine these parameters with further information, such as the presence of binding motifs, to increase prediction accuracy. PMID- 20356372 TI - In vivo trans-specific gene silencing in fungal cells by in planta expression of a double-stranded RNA. AB - BACKGROUND: Self-complementary RNA transcripts form a double-stranded RNA (dsRNA) that triggers a sequence-specific mRNA degradation, in a process known as RNA interference (RNAi), leading to gene silencing. In vascular plants, RNAi molecules trafficking occur between cells and systemically throughout the plant. RNAi signals can spread systemically throughout a plant, even across graft junctions from transgenic to non-transgenic stocks. There is also a great interest in applying RNAi to pathogenic fungi. Specific inhibition of gene expression by RNAi has been shown to be suitable for a multitude of phytopathogenic filamentous fungi. However, double-stranded (ds)RNA/small interfering (si)RNA silencing effect has not been observed in vivo. RESULTS: This study demonstrates for the first time the in vivo interference phenomenon in the pathogenic fungus Fusarium verticillioides, in which expression of an individual fungal transgene was specifically abolished by inoculating mycelial cells in transgenic tobacco plants engineered to express siRNAs from a dsRNA corresponding to the particular transgene. CONCLUSION: The results provide a powerful tool for further studies on molecular plant-microbe and symbiotic interactions. From a biotechnological perspective, silencing of fungal genes by generating siRNAs in the host provides a novel strategy for the development of broad fungi-resistance strategies in plants and other organisms. PMID- 20356373 TI - New components of the Dictyostelium PKA pathway revealed by Bayesian analysis of expression data. AB - BACKGROUND: Identifying candidate genes in genetic networks is important for understanding regulation and biological function. Large gene expression datasets contain relevant information about genetic networks, but mining the data is not a trivial task. Algorithms that infer Bayesian networks from expression data are powerful tools for learning complex genetic networks, since they can incorporate prior knowledge and uncover higher-order dependencies among genes. However, these algorithms are computationally demanding, so novel techniques that allow targeted exploration for discovering new members of known pathways are essential. RESULTS: Here we describe a Bayesian network approach that addresses a specific network within a large dataset to discover new components. Our algorithm draws individual genes from a large gene-expression repository, and ranks them as potential members of a known pathway. We apply this method to discover new components of the cAMP-dependent protein kinase (PKA) pathway, a central regulator of Dictyostelium discoideum development. The PKA network is well studied in D. discoideum but the transcriptional networks that regulate PKA activity and the transcriptional outcomes of PKA function are largely unknown. Most of the genes highly ranked by our method encode either known components of the PKA pathway or are good candidates. We tested 5 uncharacterized highly ranked genes by creating mutant strains and identified a candidate cAMP-response element-binding protein, yet undiscovered in D. discoideum, and a histidine kinase, a candidate upstream regulator of PKA activity. CONCLUSIONS: The single-gene expansion method is useful in identifying new components of known pathways. The method takes advantage of the Bayesian framework to incorporate prior biological knowledge and discovers higher-order dependencies among genes while greatly reducing the computational resources required to process high-throughput datasets. PMID- 20356374 TI - Replication independent DNA double-strand break retention may prevent genomic instability. AB - BACKGROUND: Global hypomethylation and genomic instability are cardinal features of cancers. Recently, we established a method for the detection of DNA methylation levels at sites close to endogenous DNA double strand breaks (EDSBs), and found that those sites have a higher level of methylation than the rest of the genome. Interestingly, the most significant differences between EDSBs and genomes were observed when cells were cultured in the absence of serum. DNA methylation levels on each genomic location are different. Therefore, there are more replication-independent EDSBs (RIND-EDSBs) located in methylated genomic regions. Moreover, methylated and unmethylated RIND-EDSBs are differentially processed. Euchromatins respond rapidly to DSBs induced by irradiation with the phosphorylation of H2AX, gamma-H2AX, and these initiate the DSB repair process. During G0, most DSBs are repaired by non-homologous end-joining repair (NHEJ), mediated by at least two distinct pathways; the Ku-mediated and the ataxia telangiectasia-mutated (ATM)-mediated. The ATM-mediated pathway is more precise. Here we explored how cells process methylated RIND-EDSBs and if RIND-EDSBs play a role in global hypomethylation-induced genomic instability. RESULTS: We observed a significant number of methylated RIND-EDSBs that are retained within deacetylated chromatin and free from an immediate cellular response to DSBs, the gamma-H2AX. When cells were treated with tricostatin A (TSA) and the histones became hyperacetylated, the amount of gamma-H2AX-bound DNA increased and the retained RIND-EDSBs were rapidly repaired. When NHEJ was simultaneously inhibited in TSA-treated cells, more EDSBs were detected. Without TSA, a sporadic increase in unmethylated RIND-EDSBs could be observed when Ku-mediated NHEJ was inhibited. Finally, a remarkable increase in RIND-EDSB methylation levels was observed when cells were depleted of ATM, but not of Ku86 and RAD51. CONCLUSIONS: Methylated RIND-EDSBs are retained in non-acetylated heterochromatin because there is a prolonged time lag between RIND-EDSB production and repair. The rapid cellular responses to DSBs may be blocked by compact heterochromatin structure which then allows these breaks to be repaired by a more precise ATM-dependent pathway. In contrast, Ku-mediated NHEJ can repair euchromatin-associated EDSBs. Consequently, spontaneous mutations in hypomethylated genome are produced at faster rates because unmethylated EDSBs are unable to avoid the more error-prone NHEJ mechanisms. PMID- 20356376 TI - Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series. AB - INTRODUCTION: Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. CASE PRESENTATIONS: Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. CONCLUSION: In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases. PMID- 20356375 TI - Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes. AB - BACKGROUND: Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. RESULTS: L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (rho/theta) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. CONCLUSIONS: L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two major subgroups A and B, and one atypical subgroup D serving as a link between L. monocytogenes and L. innocua in the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to environments. The evolutionary history in the L. monocytogenes-L. innocua clade represents a rare example of evolution towards reduced virulence of pathogens. PMID- 20356377 TI - Comparative genomics of metabolic networks of free-living and parasitic eukaryotes. AB - BACKGROUND: Obligate endoparasites often lack particular metabolic pathways as compared to free-living organisms. This phenomenon comprises anabolic as well as catabolic reactions. Presumably, the corresponding enzymes were lost in adaptation to parasitism. Here we compare the predicted core metabolic graphs of obligate endoparasites and non-parasites (free living organisms and facultative parasites) in order to analyze how the parasites' metabolic networks shrunk in the course of evolution. RESULTS: Core metabolic graphs comprising biochemical reactions present in the presumed ancestor of parasites and non-parasites were reconstructed from the Kyoto Encyclopedia of Genes and Genomes. While the parasites' networks had fewer nodes (metabolites) and edges (reactions), other parameters such as average connectivity, network diameter and number of isolated edges were similar in parasites and non-parasites. The parasites' networks contained a higher percentage of ATP-consuming reactions and a lower percentage of NAD-requiring reactions. Control networks, shrunk to the size of the parasites' by random deletion of edges, were scale-free but exhibited smaller diameters and more isolated edges. CONCLUSIONS: The parasites' networks were smaller than those of the non-parasites regarding number of nodes or edges, but not regarding network diameters. Network integrity but not scale-freeness has acted as a selective principle during the evolutionary reduction of parasite metabolism. ATP-requiring reactions in particular have been retained in the parasites' core metabolism while NADH- or NADPH-requiring reactions were lost preferentially. PMID- 20356378 TI - Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters. AB - BACKGROUND: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-beta1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary artery remodeling and PAH. METHODS: Hamsters were exposed to cigarette smoke; after 4 months, lung morphology and tissue biochemical changes were examined using immunohistochemistry, Western blotting, radioimmunoassay and reverse-transcription polymerase chain reaction. RESULTS: Our results show that chronic cigarette smoke exposure significantly induced elevation of right ventricular systolic pressures (RVSP) and medial hypertrophy of pulmonary arterioles in hamsters, concurrent with an increase of chymase activity and synthesis in the lung. Elevated Ang II levels and enhanced TGF beta1/Smad signaling activation were also observed in smoke-exposed lungs. Chymase inhibition with chymostatin reduced the cigarette smoke-induced increase in chymase activity and Ang II concentration in the lung, and attenuated the RVSP elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme (ACE) activity in hamster lungs. CONCLUSIONS: These results suggest that chronic cigarette smoke exposure can increase chymase activity and expression in hamster lungs. The capability of activated chymase to induce Ang II formation and TGF-beta1 signaling may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus, our study implies that blockade of chymase might provide benefits to PAH smokers. PMID- 20356379 TI - Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production. AB - BACKGROUND: Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV 1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system. RESULTS: Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs. CONCLUSION: Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron. PMID- 20356380 TI - Association between transforming growth factor beta1 polymorphisms and atrial fibrillation in essential hypertensive subjects. AB - BACKGROUND: The association of TGF beta1 polymorphisms and atrial fibrillation (AF) in essential hypertensive (EH) subjects remains unknown. Methods EH subjects with AF (EH+AF+) and sinus rhythm (EH+AF-) were enrolled. The polymorphisms of +869 T --> C at codon 10 and + 915 G --> C at codon 25, were genotyped. The clinical characteristics including serum TGF beta1 levels were detected. RESULTS: The GG genotypes of TGF beta1 +915 G --> C at codon 25 were more prevalent in subjects from EH+AF+ group than those from EH+AF- group (P = 0.009). The subjects with GG genotype from EH+AF+ group had the highest mean serum TGF beta1 level, which was significantly higher than that of GG genotype subjects from EH+AF- group (3.18 +/- 0.24 ng/dl vs.2.29 +/- 0.14 ng/dl, P < 0.05). Multiple analyses revealed that the TGF beta1 GG genotype of +915 G --> C at codon 25 presented a 3.09 times higher risk in developing AF in the multivariate model after adjusting for age and gender. CONCLUSION: The polymorphisms of TGF beta1 +915 G --> C at codon 25 were associated with occurrence of AF and serum TGF beta1 level in EH subjects. PMID- 20356381 TI - Inhibition of HIV-1 replication by small interfering RNAs directed against glioma pathogenesis related protein (GliPR) expression. AB - BACKGROUND: Previously, we showed that glioma pathogenesis related protein (GliPR) is induced in CEM T cells upon HIV-1 infection in vitro. To examine whether GliPR plays a role as HIV dependency factor (HDF), we tested the effect of GliPR suppression by siRNA on HIV-1 replication. RESULTS: Induction of GliPR expression by HIV-1 was confirmed in P4-CCR5 cells. When GliPR was suppressed by siRNA, HIV-1 replication was significantly reduced as measured by HIV-1 transcript levels, HIV-1 p24 protein levels, and HIV-1 LTR-driven reporter gene expression, suggesting that GliPR is a cellular co-factor of HIV-1. Microarray analysis of uninfected HeLa cells following knockdown of GliPR revealed, among a multitude of gene expression alterations, a down-regulation of syndecan-1, syndecan-2, protein kinase C alpha (PRKCA), the catalytic subunit beta of cAMP dependent protein kinase (PRKACB), nuclear receptor co-activator 3 (NCOA3), and cell surface protein CD59 (protectin), all genes having relevance for HIV-1 pathology. CONCLUSIONS: The up-regulation of GliPR by HIV-1 and the early significant inhibition of HIV-1 replication mediated by knockdown of GliPR reveal GliPR as an important HIV-1 dependency factor (HDF), which may be exploited for HIV-1 inhibition. PMID- 20356383 TI - Unplanned antiretroviral treatment interruptions in southern Africa: how should we be managing these? AB - Adherence to antiretroviral therapy is essential for maximising individual treatment outcomes and preventing the development of drug resistance. It is, however, frequently compromised due to predictable, but adverse, scenarios in the countries most severely affected by HIV/AIDS. This paper looks at lessons from three specific crises in southern Africa: the 2008 floods in Mozambique, the ongoing political and economic crisis in Zimbabwe, and the 2007 public sector strike in South Africa. It considers how these crises impacted on the delivery of antiretroviral therapy and looks at some of the strategies employed to mitigate any adverse effects. Based on this it makes recommendations for keeping patients on treatment and limiting the development of drug resistance where treatment interruptions are inevitable. PMID- 20356384 TI - bbThermodynamic quantities and Urmia Sea water evaporation. AB - The relation between climatic parameters (relative air humidity) and the water activity of the Urmia Sea water determines the possible maximum evaporation of the lake. Using the Pitzer thermodynamic approach, the activity of the Urmia Lake water during evaporation was calculated and compared to the present relative air humidity above the water. Present climatic conditions allow the Urmia Sea water to evaporate down to water with activity of 0.55, corresponding to the lowest air humidity measured over the lake. This water activity falls in the range of halite precipitation, while carnalite precipitation starts at somewhat lower (a H2O = 0.499) point. Our dynamic model predicts that for air humidity as low as 55% (reflecting present climate conditions), the Urmia Sea level may drop to as low as 1270 m (i. e., 1270 m above mean sea level). At that point, the lake water volume will have a volume of 11 km3. For the sake of comparison, at the beginning of 1990, the level of the lake was 1275 m, its volume was 25 km3, and its surface area was 5145 km2. PMID- 20356382 TI - Evidence based guidelines for complex regional pain syndrome type 1. AB - BACKGROUND: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. METHOD: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. RESULTS: For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS I. CONCLUSIONS: Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines. PMID- 20356385 TI - Parametric and non-parametric masking of randomness in sequence alignments can be improved and leads to better resolved trees. AB - BACKGROUND: Methods of alignment masking, which refers to the technique of excluding alignment blocks prior to tree reconstructions, have been successful in improving the signal-to-noise ratio in sequence alignments. However, the lack of formally well defined methods to identify randomness in sequence alignments has prevented a routine application of alignment masking. In this study, we compared the effects on tree reconstructions of the most commonly used profiling method (GBLOCKS) which uses a predefined set of rules in combination with alignment masking, with a new profiling approach (ALISCORE) based on Monte Carlo resampling within a sliding window, using different data sets and alignment methods. While the GBLOCKS approach excludes variable sections above a certain threshold which choice is left arbitrary, the ALISCORE algorithm is free of a priori rating of parameter space and therefore more objective. RESULTS: ALISCORE was successfully extended to amino acids using a proportional model and empirical substitution matrices to score randomness in multiple sequence alignments. A complex bootstrap resampling leads to an even distribution of scores of randomly similar sequences to assess randomness of the observed sequence similarity. Testing performance on real data, both masking methods, GBLOCKS and ALISCORE, helped to improve tree resolution. The sliding window approach was less sensitive to different alignments of identical data sets and performed equally well on all data sets. Concurrently, ALISCORE is capable of dealing with different substitution patterns and heterogeneous base composition. ALISCORE and the most relaxed GBLOCKS gap parameter setting performed best on all data sets. Correspondingly, Neighbor-Net analyses showed the most decrease in conflict. CONCLUSIONS: Alignment masking improves signal-to-noise ratio in multiple sequence alignments prior to phylogenetic reconstruction. Given the robust performance of alignment profiling, alignment masking should routinely be used to improve tree reconstructions. Parametric methods of alignment profiling can be easily extended to more complex likelihood based models of sequence evolution which opens the possibility of further improvements. PMID- 20356386 TI - Multiconstrained gene clustering based on generalized projections. AB - BACKGROUND: Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO) annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. RESULTS: We propose a novel multiconstrained gene clustering (MGC) method within the generalized projection onto convex sets (POCS) framework used widely in image reconstruction. Each constraint is formulated as a corresponding set. The generalized projector iteratively projects the clustering solution onto these sets in order to find a consistent solution included in the intersection set that satisfies all constraints. Compared with previous MGC methods, POCS can integrate multiple constraints from different nature without distorting the original constraints. To evaluate the clustering solution, we also propose a new performance measure referred to as Gene Log Likelihood (GLL) that considers genes having more than one function and hence in more than one cluster. Comparative experimental results show that our POCS-based gene clustering method outperforms current state-of-the-art MGC methods. CONCLUSIONS: The POCS-based MGC method can successfully combine multiple constraints from different nature for gene clustering. Also, the proposed GLL is an effective performance measure for the soft clustering solutions. PMID- 20356387 TI - Autotaxin expression and its connection with the TNF-alpha-NF-kappaB axis in human hepatocellular carcinoma. AB - BACKGROUND: Autotaxin (ATX) is an extracellular lysophospholipase D that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Both ATX and LPA have been shown to be involved in many cancers. However, the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma (HCC) remain elusive. RESULTS: In this study, ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects. ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis. In addition, ATX expression was examined in normal human hepatocytes and liver cancer cell lines. Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did. Proinflammtory cytokine tumor necrosis factor alpha (TNF-alpha) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells, which led to a corresponding increase in lysophospholipase-D activity. Moreover, we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B (NF-kappaB) in basal and TNF-alpha induced ATX expression. Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion. CONCLUSIONS: This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-alpha/NF-kappaB axis and the ATX LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis. PMID- 20356388 TI - Contraception for adolescents with lupus. AB - Sexually active adolescents, including young women with lupus, are at high risk for unplanned pregnancy. Unplanned pregnancy among teens with lupus is associated with an elevated risk of poor maternal and fetal outcomes. The provision of effective contraception is a crucial element of care for a sexually-active young woman with lupus. Unfortunately, providers may be hesitant to prescribe contraception to this group due to concerns about increasing the risk of lupus complications. This article reviews the risks and benefits of currently-available contraceptives for young women with lupus. Providers are encouraged to consider long-term, highly-effective contraception, such as implantables and intrauterine devices, for appropriately selected adolescents with lupus. PMID- 20356389 TI - Estimation of divergence time between two sibling species of the Anopheles (Kerteszia) cruzii complex using a multilocus approach. AB - BACKGROUND: Anopheles cruzii is the primary human Plasmodium vector in southern and southeastern Brazil. The distribution of this mosquito follows the coast of the Brazilian Atlantic Forest. Previous studies indicated that An. cruzii is a complex of cryptic species. RESULTS: A multilocus approach using six loci, three circadian clock genes and three encoding ribosomal proteins, was implemented to investigate in more detail the genetic differentiation between the An. cruzii populations from Santa Catarina (southern Brazil) and Bahia States (northeastern Brazil) that represent two sibling species. The analysis revealed very high FST values and fixed differences between the two An. cruzii sibling species in all loci, irrespective of their function. An Isolation with Migration model was fit to the data using the IM program. The results reveal no migration in either direction and allowed a rough estimate of the divergence time between the two sibling species. CONCLUSIONS: Population genetics analysis of An. cruzii samples from two Brazilian localities using a multilocus approach confirmed that they represent two different sibling species in this complex. The results suggest that the two species have not exchanged migrants since their separation and that they possibly diverged between 1.1 and 3.6 million years ago, a period of intense climatic changes. PMID- 20356391 TI - RCDI/eRCDI: a web-server to estimate codon usage deoptimization. AB - BACKGROUND: The Relative Codon Deoptimization Index (RCDI) was developed by Mueller et al. (2006) as measure of codon deoptimization by comparing how similar is the codon usage of a gene and the codon usage of a reference genome. FINDINGS: RCDI/eRCDI is a web application server that calculates the Relative Codon Deoptimization Index and a new expected value for the RCDI (eRCDI). The RCDI is used to estimate the similarity of the codon frequencies of a specific gene in comparison to a given reference genome. The eRCDI is determined by generating random sequences with similar G+C and amino acid composition to the input sequences and may be used as an indicator of the significance of the RCDI values. RCDI/eRCDI is freely available at http://genomes.urv.cat/CAIcal/RCDI. CONCLUSIONS: This web server will be a useful tool for genome analysis, to understand host-virus phylogenetic relationships or to infer the potential host range of a virus and its replication strategy, as well as in experimental virology to ease the step of gene design for heterologous protein expression. PMID- 20356390 TI - Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration. AB - BACKGROUND: Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. RESULTS: A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P < 0.01 and P < 0.05, respectively) in comparison to those indoors. Following mitogen stimulation, a lower level of interferon-gamma was produced in leukocytes from the outdoor animals (P < 0.05). There was evidence of a gastrointestinal nematode infection in the outdoor animals with elevated levels of serum pepsinogen (P < 0.001), a higher number of eosinophils (P < 0.05) and a higher level of interleukin-4 and stem cell factor mRNA expression (P < 0.05) in the outdoor animals in comparison to the indoor animals. Lower levels of copper and iodine were measured in the outdoor animals in comparison to indoor animals (P < 0.001). CONCLUSION: Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system. PMID- 20356393 TI - Primary tubercular caecal perforation: a rare clinical entity. AB - BACKGROUND: Intestinal tuberculosis is a common problem in endemic areas, causing considerable morbidity and mortality. An isolated primary caecal perforation of tubercular origin is exceptionally uncommon. CASE PRESENTATION: We report the case of a 39 year old male who presented with features of perforation peritonitis, which on laparotomy revealed a caecal perforation with a dusky appendix. A standard right hemicolectomy with ileostomy and peritoneal toileting was done. Histopathology revealed multiple transmural caseating granulomas with Langerhans-type giant cells and acid-fast bacilli, consistent with tuberculosis, present only in the caecum. CONCLUSIONS: We report this extremely rare presentation of primary caecal tuberculosis to sensitize the medical fraternity to its rare occurrence, which will be of paramount importance owing to the increasing incidence of tuberculosis all over the world, especially among the developing countries. PMID- 20356392 TI - Effect of dipterinyl calcium pentahydrate on hepatitis B virus replication in transgenic mice. AB - BACKGROUND: Dipterinyl calcium pentahydrate (DCP) has previously been shown to inhibit MDA-MB-231 human breast cancer xenographs in nude mice in a manner correlated with increases in plasma IL-12 and IL-4 concentrations, and decreases in plasma IL-6 levels. DCP also inhibits indoleamine 2,3-dioxygenase (IDO), an immuno-inhibitory enzyme, in human PBMCs (Peripheral Blood Mononuclear Cells). METHODS: In the present study, DCP was administered per os, once daily for 14 days to hepatitis B virus (HBV) transgenic mice at 23, 7.3, and 2.3 mg/(kg d). Multivariate stepwise regression and MANOVA analyses, by gender and treatment, of liver HBV DNA and RNA measures, liver core and serum HBe antigen assays, serum cytokine/chemokine profiles, and IDO metabolite measurements were performed. RESULTS: DCP caused a significant dose-response reduction of log liver HBV DNA as measured by PCR in the female HBV mice. The gender dependence of the anti-HBV DNA activity was explained by the DCP Effects Model (DCP-EM) (p = .001) which includes three serum biomarker changes caused by DCP: 1) decreased MCP-1; 2) decreased Kyn/Trp (an estimation of IDO activity); and 3) increased GM-CSF. CONCLUSIONS: Immunomodulation via IDO or TDO (tryptophan 2,3-dioxygenase) pathways, along with serum MCP-1 and GM-CSF are proposed to play roles in the anti-HBV mechanism of DCP based upon their coordinated modulation in the reduction of viral DNA replication in HBV mice. PMID- 20356394 TI - Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements. AB - BACKGROUND: Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/). METHODS: SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2 /- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. RESULTS: When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. CONCLUSION: Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer resistance in SR/CR mice. The resistance was functional when any one of these effector mechanisms was completely absent, except some noticeably reduced penetrance, but not abolishment, of the phenotype in the male background in comparison to female background. These results also indicate that some other effector mechanism(s) of granulocytes may be involved in the killing of cancer cells in SR/CR mice. PMID- 20356396 TI - Enteritis caused by Campylobacter jejuni followed by acute motor axonal neuropathy: a case report. AB - INTRODUCTION: Campylobacter species represent the main cause of bacterial diarrhea in developed countries and one of the most frequent causes of enterocolitis in developing ones. In some patients, Campylobacter jejuni infection of the gastrointestinal tract has been observed as an antecedent illness of acute motor axonal neuropathy, a variant of Guillain-Barre syndrome. CASE PRESENTATION: We present a case of acute motor axonal neuropathy following infection with Campylobacter jejuni subspecies jejuni, biotype II, heat stable serotype O:19. A 46-year-old Caucasian man developed acute motor neuropathy 10 days after mild intestinal infection. The proximal and distal muscle weakness of his upper and lower extremities was associated with serum antibodies to Campylobacter jejuni and antibodies to ganglioside GM1. The electromyographic signs of neuropathic muscle action potentials with almost normal nerve conduction velocities indicated axonal neuropathy. Our patient's clinical and electrophysiological features fulfilled criteria for the diagnosis of an acute motor axonal neuropathy, a subtype of Guillain-Barre syndrome. CONCLUSION: As this is the first case of acute motor axonal neuropathy following infection with Campylobacter jejuni subspecies jejuni reported from the Balkan area, the present findings indicate the need for systematic studies and further clinical, epidemiological and microbiological investigations on the prevalence of Campylobacter jejuni and its heat stable serotypes in the etiology of Guillain Barre syndrome and other post-infectious sequelae. PMID- 20356395 TI - Comparison of yoga versus stretching for chronic low back pain: protocol for the Yoga Exercise Self-care (YES) trial. AB - BACKGROUND: Back pain, one of the most prevalent conditions afflicting American adults, is the leading reason for using complementary and alternative medicine (CAM) therapies. Yoga is an increasingly popular "mind-body" CAM therapy often used for relieving back pain and several small studies have found yoga effective for this condition. This study will assess whether yoga is effective for treating chronic low back pain compared with self care and exercise and will explore the mechanisms responsible for any observed benefits. METHODS/DESIGN: A total of 210 participants with low back pain lasting at least 3 months will be recruited from primary care clinics of a large healthcare system based in Seattle. They will be randomized in a 2:2:1 ratio to receive 12 weekly yoga classes, 12 weekly conventional therapeutic exercise classes of comparable physical exertion, or a self-care book. Interviewers masked to participants' treatment group will assess outcomes at baseline and 6, 12 and 26 weeks after randomization. Primary outcomes will be back-related dysfunction and symptom bothersomeness. In addition, data will be collected on physical measurements (e.g., flexion) at baseline and 12 weeks and saliva samples will be obtained at baseline, 6 and 12 weeks. Information will be collected on specific physical, psychological, and physiological factors to allow exploration of possible mechanisms of action through which yoga could relieve back pain and dysfunction. The effectiveness of yoga will be assessed using analysis of covariance (using general estimating equations - GEE) within an intention-to-treat context. If yoga is found effective, further analyses will explore whether yoga's benefits are attributable to physical, psychological and/or physiological factors. CONCLUSIONS: This study will provide the clearest evidence to date about the value of yoga as a therapeutic option for treating chronic back pain, and if the results are positive, will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study. PMID- 20356397 TI - Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats. AB - BACKGROUND: Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat. METHODS: A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged in vivo by intraperitoneal injection into immunocompetent Lewis rats, and in vitro culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor alpha, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. beta catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines. RESULTS: The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line in vitro, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor alpha, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear beta-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma. CONCLUSION: This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies. PMID- 20356398 TI - Evaluation of three PCR-based diagnostic assays for detecting mixed Plasmodium infection. AB - BACKGROUND: One of the most commonly used molecular test for malaria diagnosis is the polymerase chain reaction (PCR)-based amplification of the 18S ribosomal DNA (rDNA) gene. Published diagnostic assays based on the 18S gene include the "gold standard" nested assay, semi-nested multiplex assay, and one tube multiplex assay. To our knowledge, no one has reported whether the two multiplex methods are better at detecting mixed Plasmodium infections compared to the nested assay using known quantities of DNA in experimentally mixed cocktails. FINDINGS: Here we evaluated three PCR assays (nested, semi-nested multiplex, and one-tube multiplex) for the simultaneous detection of human malaria parasites using experimentally mixed cocktails of known quantities of laboratory derived DNA. All three assays detected individual species with high sensitivity and specificity when DNA was from any one single species; however, experimentally mixed DNA cocktails with all four species present were correctly identified most consistently with the nested method. The other two methods failed to consistently identify all four species correctly, especially at lower concentrations of DNA subclinical levels of malaria (DNA equivalent to or less than 10 parasites per microliter). CONCLUSIONS: The nested PCR method remains the method of choice for the detection of mixed malaria infections and especially of sub-clinical infections. Further optimization and/or new molecular gene targets may improve the success rate of detecting multiple parasite species simultaneously using traditional PCR assays. PMID- 20356399 TI - Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study. AB - BACKGROUND: Streptococcus pneumoniae is the most significant bacterial cause of community-acquired pneumonia among children under five years worldwide. Updated resistance information of S. pneumoniae among children is essential to adjust the recommendations for empirical treatment of community-acquired pneumonia, which will have immense implications for local and global health. This study investigated the prevalence of antibiotic resistance in isolated strains of S. pneumoniae and relationship with antibiotic use and demographic factors of children under five in rural Vietnam in 2007. METHODS: In Bavi district, 847 children 6 to 60 months were selected from 847 households. The main child caregivers in the households were interviewed weekly using structured questionnaires to collect information of daily illness symptoms and drug use for the selected child over a four-week period (from March through June 2007). In the 3rd week, the children were invited for a clinical examination and to collect nasopharyngeal samples for S. pneumoniae identification. Etest and disk diffusion were used to test antibiotic susceptibility. RESULTS: Of 818 participating children, 258 (32%) had ongoing respiratory infections, 421 (52%) carried S. pneumoniae, and 477 (58%) had used antibiotics within the previous three weeks. Of the 421 isolates, 95% were resistant to at least one antibiotic (401/421). Resistance to co-trimoxazole, tetracycline, phenoxymethylpenicillin, erythromycin and ciprofloxacin was 78%, 75%, 75%, 70% and 28%, respectively. Low resistance was noted for amoxicillin (4%), benzylpenicillin (4%), and cefotaxime (2%). The intermediate resistance to amoxicillin was 32%. Multidrug-resistance was seen in 60%. The most common pattern was co-resistance to co-trimoxazole, tetracycline and erythromycin. The proportion of children carrying resistant bacteria was higher among the children who had used antibiotics in the previous three weeks. CONCLUSIONS: Resistance to commonly used antibiotics and multidrug-resistance of S. pneumoniae in the area is remarkably high. High-dose amoxicillin is the only investigated oral antibiotic that can possibly be used for treatment of community acquired pneumococcal infections. Strategies to promote appropriate prescribing and dispensing of effective antibiotics should be immediately implemented for the benefit of local and global health. PMID- 20356400 TI - Differing effect of systemic anti psoriasis therapies on platelet physiology--a case report and review of literature. AB - BACKGROUND: Psoriasis is a common, chronic relapsing inflammatory skin disease. Lately, there is increasing evidence that psoriasis is more than "skin deep". Epidemiological studies showed that severe psoriasis might have also important systemic manifestations such as metabolic deregulations, cardiovascular disease (CVD) and increased mortality. Moreover, recently psoriasis patients were found to have platelet hyperactivity. CASE PRESENTATION: This is a case report and review of the literature. We present a patient with long standing severe psoriasis vulgaris with marked thrombocytosis. His thrombocytosis did not correlate with disease severity but rather with the different treatments that he was exposed to, subsiding only during treatment with anti Tumor Necrosis Factor (TNF)- agents. A literature review revealed that in rheumatoid arthritis, another systemic inflammatory disease; interleukin (IL)-6 might be implicated in causing thrombocytosis. CONCLUSION: This unique case report illustrates that different systemic treatments for psoriasis might have implications beyond the care of skin lesions. This insight is especially important in psoriasis patients in view of their deranged hemostatic balance toward a prothrombotic state, which might increase the risk of thrombosis and CVD. Therefore, further studies analyzing the effect of different drugs on platelets physiology are warranted. PMID- 20356401 TI - Paraganglioma of the mediastinum: challenges in diagnosis and surgical management. AB - Mediastinal paraganglioms are rare, highly vascularized tumors arising from chromaffin tissue located in the para-aortic ganglia. Tumors tend to invade bordering structures and may also form metastasis. Up to 50% of patients are asymptomatic and diagnosis is incidental. Presenting symptoms are related to catecholamine hypersecretion or to a mass effect. Complete surgical resection remains the standard of care due to malignant potential of the tumor and poor response to chemotherapy or radiation. Strategic location of the tumor in proximity to great vessels, trachea, and recurrent laryngeal nerve poses challenge for the surgeon. We report a case of a 59-year old asymptomatic female who was incidentally diagnosed with a middle mediastinal mass on a positron emission tomography (PET-CT) scan performed as part of breast cancer surveillance. Complete resection of the tumor was achieved using cardiopulmonary bypass. The patient recovered uneventfully and in a ten-month follow up there is no evidence of recurrence. PMID- 20356402 TI - Oxygenation-sensitive CMR for assessing vasodilator-induced changes of myocardial oxygenation. AB - BACKGROUND: As myocardial oxygenation may serve as a marker for ischemia and microvascular dysfunction, it could be clinically useful to have a non-invasive measure of changes in myocardial oxygenation. However, the impact of induced blood flow changes on oxygenation is not well understood. We used oxygenation sensitive CMR to assess the relations between myocardial oxygenation and coronary sinus blood oxygen saturation (SvO2) and coronary blood flow in a dog model in which hyperemia was induced by intracoronary administration of vasodilators. RESULTS: During administration of acetylcholine and adenosine, CMR signal intensity correlated linearly with simultaneously measured SvO2 (r2 = 0.74, P < 0.001). Both SvO2 and CMR signal intensity were exponentially related to coronary blood flow, with SvO2 approaching 87%. CONCLUSIONS: Myocardial oxygenation as assessed with oxygenation-sensitive CMR imaging is linearly related to SvO2 and is exponentially related to vasodilator-induced increases of blood flow. Oxygenation-sensitive CMR may be useful to assess ischemia and microvascular function in patients. Its clinical utility should be evaluated. PMID- 20356403 TI - Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression. AB - The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES) cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC) populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR) based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them. Six known pseudogenes exist for Oct4, all of which exhibit very high sequence homology (three >97%), and for this reason the generation of artefacts may have contributed to false identification of Oct4 in somatic cell populations. While ASC lack a molecular blueprint of transcription factors proposed to be involved with 'stemness' as described for ES cells, it is not unreasonable to assume that similar gene patterns may exist. The focus of this work was to corroborate reports that Oct4 is involved in the regulation of ASC self-renewal and differentiation, using a combination of methodologies to rule out pseudogene interference. Haematopoietic stem cells (HSC) derived from human umbilical cord blood (UCB) and various differentiated cell lines underwent RT-PCR, product sequencing and transfection studies using an Oct4 promoter-driven reporter. In summary, only the positive control expressed Oct4, with all other cell types expressing a variety of Oct4 pseudogenes. Somatic cells were incapable of utilising an exogenous Oct4 promoter construct, leading to the conclusion that Oct4 does not appear involved in the multipotency of human HSC from UCB. PMID- 20356404 TI - Little genetic differentiation as assessed by uniparental markers in the presence of substantial language variation in peoples of the Cross River region of Nigeria. AB - BACKGROUND: The Cross River region in Nigeria is an extremely diverse area linguistically with over 60 distinct languages still spoken today. It is also a region of great historical importance, being a) adjacent to the likely homeland from which Bantu-speaking people migrated across most of sub-Saharan Africa 3000 5000 years ago and b) the location of Calabar, one of the largest centres during the Atlantic slave trade. Over 1000 DNA samples from 24 clans representing speakers of the six most prominent languages in the region were collected and typed for Y-chromosome (SNPs and microsatellites) and mtDNA markers (Hypervariable Segment 1) in order to examine whether there has been substantial gene flow between groups speaking different languages in the region. In addition the Cross River region was analysed in the context of a larger geographical scale by comparison to bordering Igbo speaking groups as well as neighbouring Cameroon populations and more distant Ghanaian communities. RESULTS: The Cross River region was shown to be extremely homogenous for both Y-chromosome and mtDNA markers with language spoken having no noticeable effect on the genetic structure of the region, consistent with estimates of inter-language gene flow of 10% per generation based on sociological data. However the groups in the region could clearly be differentiated from others in Cameroon and Ghana (and to a lesser extent Igbo populations). Significant correlations between genetic distance and both geographic and linguistic distance were observed at this larger scale. CONCLUSIONS: Previous studies have found significant correlations between genetic variation and language in Africa over large geographic distances, often across language families. However the broad sampling strategies of these datasets have limited their utility for understanding the relationship within language families. This is the first study to show that at very fine geographic/linguistic scales language differences can be maintained in the presence of substantial gene flow over an extended period of time and demonstrates the value of dense sampling strategies and having DNA of known and detailed provenance, a practice that is generally rare when investigating sub-Saharan African demographic processes using genetic data. PMID- 20356405 TI - The association between subchondral bone cysts and tibial cartilage volume and risk of joint replacement in people with knee osteoarthritis: a longitudinal study. AB - INTRODUCTION: To examine the natural history of subchondral bone cysts and to determine whether knee cartilage loss and risk of joint replacement is higher in knees with cysts, compared with those with bone marrow lesions (BMLs) only or those with neither BMLs nor cysts. METHODS: The symptomatic knee in 132 subjects with knee osteoarthritis (OA) was imaged by using magnetic resonance imaging at baseline and 2 years later. Tibial cartilage volume, subchondral bone cysts, and BMLs were measured by using validated methods. Knee arthroplasty over a 4-year period was ascertained. RESULTS: Bone cysts were present in 47.7% of subjects, 98.1% of whom also had BMLs. Over a 2-year period, 23.9% of subjects had cysts progress, 13.0% developed new cysts, and 11.4% had cysts regress. Bone cysts at baseline were associated with lower medial and lateral tibial cartilage volume compared with those with BMLs only or those with neither (P for trend 0.004 and <0.001, respectively). Annual medial cartilage volume loss was greatest in those with bone cysts compared with those with BMLs only or those with neither (9.3%, 6.3%, and 2.6%, respectively; P for trend, <0.001). As the severity of bone abnormality in the medial compartment increased from no BMLs or cysts present, to BMLs only, to subchondral bone cysts present, the risk of knee replacement was increased (odds ratio, 1.99; 95% confidence interval (CI), 1.01 to 3.90; P = 0.05). CONCLUSIONS: When cysts are present, cartilage loss and risk of knee replacement are higher than if only BMLs are present, suggesting that cysts identify those most likely to benefit from prevention of disease progression. As cysts can regress, they may also provide therapeutic targets in knee OA. PMID- 20356406 TI - Discriminating between rival biochemical network models: three approaches to optimal experiment design. AB - BACKGROUND: The success of molecular systems biology hinges on the ability to use computational models to design predictive experiments, and ultimately unravel underlying biological mechanisms. A problem commonly encountered in the computational modelling of biological networks is that alternative, structurally different models of similar complexity fit a set of experimental data equally well. In this case, more than one molecular mechanism can explain available data. In order to rule out the incorrect mechanisms, one needs to invalidate incorrect models. At this point, new experiments maximizing the difference between the measured values of alternative models should be proposed and conducted. Such experiments should be optimally designed to produce data that are most likely to invalidate incorrect model structures. RESULTS: In this paper we develop methodologies for the optimal design of experiments with the aim of discriminating between different mathematical models of the same biological system. The first approach determines the 'best' initial condition that maximizes the L2 (energy) distance between the outputs of the rival models. In the second approach, we maximize the L2-distance of the outputs by designing the optimal external stimulus (input) profile of unit L2-norm. Our third method uses optimized structural changes (corresponding, for example, to parameter value changes reflecting gene knock-outs) to achieve the same goal. The numerical implementation of each method is considered in an example, signal processing in starving Dictyostelium amoebae. CONCLUSIONS: Model-based design of experiments improves both the reliability and the efficiency of biochemical network model discrimination. This opens the way to model invalidation, which can be used to perfect our understanding of biochemical networks. Our general problem formulation together with the three proposed experiment design methods give the practitioner new tools for a systems biology approach to experiment design. PMID- 20356407 TI - Initial development and structure of biofilms on microbial fuel cell anodes. AB - BACKGROUND: Microbial fuel cells (MFCs) rely on electrochemically active bacteria to capture the chemical energy contained in organics and convert it to electrical energy. Bacteria develop biofilms on the MFC electrodes, allowing considerable conversion capacity and opportunities for extracellular electron transfer (EET). The present knowledge on EET is centred around two Gram-negative models, i.e. Shewanella and Geobacter species, as it is believed that Gram-positives cannot perform EET by themselves as the Gram-negatives can. To understand how bacteria form biofilms within MFCs and how their development, structure and viability affects electron transfer, we performed pure and co-culture experiments. RESULTS: Biofilm viability was maintained highest nearer the anode during closed circuit operation (current flowing), in contrast to when the anode was in open circuit (soluble electron acceptor) where viability was highest on top of the biofilm, furthest from the anode. Closed circuit anode Pseudomonas aeruginosa biofilms were considerably thinner compared to the open circuit anode (30 +/- 3 microm and 42 +/- 3 microm respectively), which is likely due to the higher energetic gain of soluble electron acceptors used. The two Gram-positive bacteria used only provided a fraction of current produced by the Gram-negative organisms. Power output of co-cultures Gram-positive Enterococcus faecium and either Gram-negative organisms, increased by 30-70% relative to the single cultures. Over time the co culture biofilms segregated, in particular, Pseudomonas aeruginosa creating towers piercing through a thin, uniform layer of Enterococcus faecium. P. aeruginosa and E. faecium together generated a current of 1.8 +/- 0.4 mA while alone they produced 0.9 +/- 0.01 and 0.2 +/- 0.05 mA respectively. CONCLUSION: We postulate that this segregation may be an essential difference in strategy for electron transfer and substrate capture between the Gram-negative and the Gram positive bacteria used here. PMID- 20356408 TI - Investigation of relative risk estimates from studies of the same population with contrasting response rates and designs. AB - BACKGROUND: There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate ~60%). METHODS: Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights. RESULTS: Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly. CONCLUSIONS: These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items. PMID- 20356409 TI - Semi-parametric risk prediction models for recurrent cardiovascular events in the LIPID study. AB - BACKGROUND: Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome. However, in many situations, recurrent event data are frequently observed. It is inefficient to use methods for the analysis of first events to analyse recurrent event data. METHODS: We applied several semi-parametric proportional hazards models to analyze the risk of recurrent myocardial infarction (MI) events based on data from a very large randomized placebo-controlled trial of cholesterol lowering drug. The backward selection procedure was used to select the significant risk factors in a model. The best fitting model was selected using the log-likelihood ratio test, Akaike Information and Bayesian Information Criteria. RESULTS: A total of 8557 persons were included in the LIPID study. Risk factors such as age, smoking status, total cholesterol and high density lipoprotein cholesterol levels, qualifying event for the acute coronary syndrome, revascularization, history of stroke or diabetes, angina grade and treatment with pravastatin were significant for development of both first and subsequent MI events. No significant difference was found for the effects of these risk factors between the first and subsequent MI events. The significant risk factors selected in this study were the same as those selected by the parametric conditional frailty model. Estimates of the relative risks and 95% confidence intervals were also similar between these two methods. CONCLUSIONS: Our study shows the usefulness and convenience of the semi-parametric proportional hazards models for the analysis of recurrent event data, especially in estimation of regression coefficients and cumulative risks. PMID- 20356411 TI - Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram. AB - BACKGROUND: With an accumulation of in silico data obtained by simulating large scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells. Investigating the dynamic features of current computational models promises a deeper understanding of complex cellular processes. This leads us to develop a method that utilizes structural properties of the model over all simulation time steps. Further, user friendly overviews of dynamic behaviors can be considered to provide a great help in understanding the variations of system mechanisms. RESULTS: We propose a novel method for constructing and analyzing a so-called active state transition diagram (ASTD) by using time-course simulation data of a high-level Petri net. Our method includes two new algorithms. The first algorithm extracts a series of subnets (called temporal subnets) reflecting biological components contributing to the dynamics, while retaining positive mathematical qualities. The second one creates an ASTD composed of unique temporal subnets. ASTD provides users with concise information allowing them to grasp and trace how a key regulatory subnet and/or a network changes with time. The applicability of our method is demonstrated by the analysis of the underlying model for circadian rhythms in Drosophila. CONCLUSIONS: Building ASTD is a useful means to convert a hybrid model dealing with discrete, continuous and more complicated events to finite time-dependent states. Based on ASTD, various analytical approaches can be applied to obtain new insights into not only systematic mechanisms but also dynamics. PMID- 20356412 TI - Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases. AB - BACKGROUND: Phospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Straussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals. METHODS: The profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3beta and CDK5 in the brains were tested. RESULTS: The contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3beta transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events. CONCLUSION: These data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3beta and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases. PMID- 20356413 TI - Motif Enrichment Analysis: a unified framework and an evaluation on ChIP data. AB - BACKGROUND: A major goal of molecular biology is determining the mechanisms that control the transcription of genes. Motif Enrichment Analysis (MEA) seeks to determine which DNA-binding transcription factors control the transcription of a set of genes by detecting enrichment of known binding motifs in the genes' regulatory regions. Typically, the biologist specifies a set of genes believed to be co-regulated and a library of known DNA-binding models for transcription factors, and MEA determines which (if any) of the factors may be direct regulators of the genes. Since the number of factors with known DNA-binding models is rapidly increasing as a result of high-throughput technologies, MEA is becoming increasingly useful. In this paper, we explore ways to make MEA applicable in more settings, and evaluate the efficacy of a number of MEA approaches. RESULTS: We first define a mathematical framework for Motif Enrichment Analysis that relaxes the requirement that the biologist input a selected set of genes. Instead, the input consists of all regulatory regions, each labeled with the level of a biological signal. We then define and implement a number of motif enrichment analysis methods. Some of these methods require a user-specified signal threshold, some identify an optimum threshold in a data driven way and two of our methods are threshold-free. We evaluate these methods, along with two existing methods (Clover and PASTAA), using yeast ChIP-chip data. Our novel threshold-free method based on linear regression performs best in our evaluation, followed by the data-driven PASTAA algorithm. The Clover algorithm performs as well as PASTAA if the user-specified threshold is chosen optimally. Data-driven methods based on three statistical tests-Fisher Exact Test, rank-sum test, and multi-hypergeometric test--perform poorly, even when the threshold is chosen optimally. These methods (and Clover) perform even worse when unrestricted data-driven threshold determination is used. CONCLUSIONS: Our novel, threshold free linear regression method works well on ChIP-chip data. Methods using data driven threshold determination can perform poorly unless the range of thresholds is limited a priori. The limits implemented in PASTAA, however, appear to be well chosen. Our novel algorithms--AME (Analysis of Motif Enrichment)-are available at http://bioinformatics.org.au/ame/. PMID- 20356414 TI - Retirement intentions of dentists in New South Wales, Australia. AB - BACKGROUND: The Australian dental workforce is ageing and current shortages have been predicted to worsen with the retirement of the growing contingent of older dentists. However, these predictions have been based on retirement trends of previous generations and little is known about the retirement intentions of today's older dentists. METHODS: The Dentist Retirement Intentions Survey was mailed to 768 NSW Australian Dental Association members aged over 50 and achieved a response rate of 20%. T-tests, ANOVAs and multivariate regression were used to analyse the data. RESULTS: On average, participants intend to retire at the age of 66, although they would prefer to do so earlier (p<0.05). Those intending to leave the workforce within the next 5 years represent 43%. The most common reasons dentists expect to retire are to have more leisure time, to be able to afford to stop working, and job stress or pressure. CONCLUSIONS: The current generation of older dentists intends to retire later than their predecessors. Most wish to remain involved in dentistry in some capacity following retirement, and may assist in overcoming workforce shortages, either by practising part time or training dental students. PMID- 20356410 TI - Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease. AB - BACKGROUND: Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. METHODS: We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. RESULTS: The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83-1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. CONCLUSIONS: These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute to the risk of familial PD. PMID- 20356417 TI - Psychiatric disorder as clinical presentation of primary Sjogren's syndrome: two case reports. AB - Psychiatric disorders in primary Sjogren's syndrome constitute a possible clinical reality that each practitioner must be able to recognise and treat. In this article, two case reports of mental disorder as clinical presentation of primary Sjogren's syndrome are presented, suggesting that psychiatric manifestations in primary Sjogren's syndrome can occur not only during its longitudinal course, but also at the onset of the autoimmune syndrome. A better adapted prescription of corticosteroids and/or immunosuppressive agents (together with specific psychotropic treatments) can induce rapid relief of mental symptoms. PMID- 20356416 TI - "Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression". AB - BACKGROUND: In damaged organs tissue repair and replacement of cells by connective tissue provokes a response of fibroblasts to cellular stress factors such as hypoxia.MicroRNAs (miRNA) are small non-coding RNA molecules which bind to their mRNA targets which eventually lead to repression of translation. Whether the response of fibroblasts to stress factors also involves the miRNA system is largely unknown. RESULTS: By miRNA profiling we identified down-regulation of miRNA-449a/b expression in hypoxic fibroblasts. Specific miRNA inhibitors and mimics showed direct evidence for targeting the serine protease inhibitor (serpin) protein (SERPINE1; plasminogen activator inhibitor-1, PAI-1) by miRNA 449a/b leading to SERPINE1 mRNA and protein up- and down-regulation, respectively. SERPINE1 expression in vivo could be located predominantly in areas of fibrosis and remodeling. CONCLUSIONS: Our study offers serious lines of evidence for a novel hypoxia-dependent mechanism involving hypoxia-induced decrease of clustered miRNA-449a/b, hypoxia-induced amplification of concomitant increase of targeted SERPINE1 (PAI-1) and its overexpression in tissues showing a hypoxic environment. PMID- 20356415 TI - Tropomyosin3 overexpression and a potential link to epithelial-mesenchymal transition in human hepatocellular carcinoma. AB - BACKGROUND: Since hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, it is still important to understand hepatocarcinogenesis mechanisms and identify effective markers for tumor progression to improve prognosis. Amplification and overexpression of Tropomyosin3 (TPM3) are frequently observed in HCC, but its biological meanings have not been properly defined. In this study, we aimed to elucidate the roles of TPM3 and related molecular mechanisms. METHODS: TPM3-siRNA was transfected into 2 HCC cell lines, HepG2 and SNU-475, which had shown overexpression of TPM3. Knockdown of TPM3 was verified by real-time qRT-PCR and western blotting targeting TPM3. Migration and invasion potentials were examined using transwell membrane assays. Cell growth capacity was examined by colony formation and soft agar assays. RESULTS: Silencing TPM3 resulted in significant suppression of migration and invasion capacities in both HCC cell lines. To elucidate the mechanisms behind suppressed migration and invasiveness, we examined expression levels of Snail and E-cadherin known to be related to epithelial-mesenchymal transition (EMT) after TPM3 knockdown. In the TPM3 knockdown cells, E-cadherin expression was significantly upregulated and Snail downregulated compared with negative control. TPM3 knockdown also inhibited colony formation and anchorage independent growth of HCC cells. CONCLUSIONS: Based on our findings, we formulate a hypothesis that overexpression of TPM3 activates Snail mediated EMT, which will repress E-cadherin expression and that it confers migration or invasion potentials to HCC cells during hepatocarcinogenesis. To our knowledge, this is the first evidence that TPM3 gets involved in migration and invasion of HCCs by modifying EMT pathway. PMID- 20356419 TI - [Ingrown toenail]. AB - Three patients, men aged 58, 79 and 78 years, with onychocryptosis in their right, left and right hallux respectively, were treated by partial nail extraction and phenolisation of the nail bed. The wound did not heal and the symptoms worsened. The ankle-brachial index was < 0.9, which is an indication of peripheral arterial disease. This was confirmed by ultrasonography, CT and magnetic resonance angiography (MRA). In the first patient, endovascular arterial dilatation did not result in enough circulation and hallux amputation was needed. The second patient recovered after a femorofibular bypass, and the third one after a femoropopliteal bypass. Treatment of ingrown toenails might result in major complications, if a patient suffers from known or unknown peripheral arterial disease. If an ingrown toenail needs surgical treatment, efforts should be made to determine whether the patient suffers from peripheral arterial disease. This can be done by interviewing the patient, physical examination and measuring the ankle-brachial index. For diabetic patients the ankle-brachial index is not reliable; therefore toe pressure waves should be measured before surgical treatment. If signs of peripheral arterial disease are detected, the patient should be referred to the vascular surgeon before surgical treatment of the ingrown toenail. PMID- 20356418 TI - N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry. AB - BACKGROUND: The post-translational modification of proteins, including glycosylation, differs between normal and tumor cells. The UDP-N-acetyl-D galactosamine polypeptide N-acetylgalactosaminyltransferases (GalNAc-Tases) family of enzymes regulates the initial steps of mucin O-glycosylation and is responsible for the altered glycosylation state observed in cancer cells. Recently it was found that GalNAc-T14 mRNA is heterogeneously expressed in breast carcinomas compared to normal tissue, however the expression profile of GalNAc T14 protein in breast carcinomas compared to normal tissue is still unknown. In this study, we assessed the expression profile of GalNAc-T14 protein in malignant and non-malignant breast tissues by immunohistochemistry to evaluate whether GalNAc-T14 might be a potential biomarker for breast cancer. METHODS: In formalin fixed tissues, the expression level of GalNAc-T14 protein was evaluated by immunohistochemistry assay in breast tissues. Expression profiles were assessed in normal tissues, benign fibroadenomas and several types of carcinomas. RESULTS: Our results showed that GalNAc-T14 was heterogeneously expressed in breast carcinomas compared to non-malignant tissue. GalNAc-T14 expression was observed in 47/56 (83.9%) carcinoma samples, 7/48 (14.6%) non-malignant breast tissue samples. GalNAc-T14 expression level was associated with histological grade. For this enzyme a significant association with invasive ductal type, mucinous adenocarcinoma and ductal carcinoma in situ (DCIS) type was found. CONCLUSION: Our results provide evidence that GalNAc-T14 may be a potential biomarker for breast cancer by immunohistochemistry. GalNAc-T14 expression level was associated with histological grade. GalNAc-T14 expression can provide new insights about breast cancer glycobiology. PMID- 20356421 TI - [Pathophysiology of one warm foot. Anatomy of the autonomic nervous system]. AB - A 50-year-old man presented with a persistently warm left foot, which did not perspire. What initially seemed to be an innocent disorder turned out to be a retroperitoneal germ cell tumour situated at Liii-Liv. In most people this location is the site of the lumbar paravertebral ganglia (an important part of the sympathetic nervous system). The fact that these ganglia were affected by the tumour explained the autonomic dysfunction in this case. The patient received curative chemotherapy. Exploration of the symptoms with respect to the pathophysiology and anatomy of the autonomous nervous system might have led to an earlier diagnosis. PMID- 20356422 TI - [Meningoencephalitis caused by varicella zoster virus]. AB - Varicella zoster virus (VZV) belongs to the group of herpes viruses. It can cause a number of nervous system infections. We present 2 of 4 patients seen recently suffering from acute meningoencephalitis, in which VZV proved to be the infectious agent. The first patient was a 57-year-old woman with headache, vomiting, and sudden aggressiveness. The second patient was a 60-year-old man with headache, nausea, and vomiting. Neither patient had skin eruptions usually associated with VZV reactivation, nor had either recently suffered from herpes zoster. Both patients had in their cerebrospinal fluid a lymphocytic pleocytosis, a decreased glucose concentration and and an elevated protein concentration. The patients recovered within a few days of starting intravenous treatment with aciclovir 10 mg/kg 3 times daily for one week. Recent literature shows that VZV is a common pathogen in meningoencephalitis and is probably underestimated as a putative cause of this condition. VZV meningoencephalitis usually has a mild course, but serious complications have been reported. Patients present with headache and usually fever. Nuchal rigidity and meningeal irritation are not always present. Since the advent of the PCR technique, VZV has been readily demonstrable. Anti-viral treatment is advised despite the lack of placebo controlled studies, and may be combined with prednisone. PMID- 20356423 TI - [Does ultraclean air in the operating room provide greater safety?]. AB - The Dutch quality control plan for climatisation of the operating room (OR), which was published in 2005, describes the management and maintenance of the air conditioning system. This management plan proposes a standard for air quality in class 1 ORs. This has been adopted by the Dutch Orthopaedic Society, but not by other surgical societies. The British study which underlies the proposed norm for air quality in class 1 ORs, a study on the infection preventive effect of ultraclean air, dates from 1982 and is inadequately controlled for prophylactic use of antibiotics. Antibiotic prophylaxis in itself already reduces the number of surgical site infections.-More recent studies fail to show an infection preventive effect of ultraclean air in the OR. The Dutch Working Party for Infection Prevention (WIP) ought to take the initiative, together with the medical Scientific Societies and the Society of Infection Prevention and Control in the health care setting (VHIG), to establish enforceable norms for microbiological air quality and to set criteria as to which types of operations are allowed to be performed in which class of OR. PMID- 20356424 TI - [Performance indicators: the role of 'task uncertainty']. AB - In recent years, quality of care has occupied a prominent place in health care. Different performance indicators are used to assess the quality of care. There is some debate about the value of outcome versus process indicators in measuring aspects of quality of care. Van de Geer et al. carried out a field study in a medical rehabilitation centre in the Netherlands in which four low task uncertainty teams ('hand trauma', 'heart failure', 'amputation', 'chronic pain'), and four high task uncertainty teams ('children with developmental coordination disorder', 'Parkinson disease', 'young children (aged 1-4 years) with developmental disorders', 'acquired brain injuries') participated in the development of performance indicators. They concluded that task uncertainty is an important factor to be considered in the development of indicators, and in the choice between the use of process and outcome indicators. Notably, outcome indicators are only useful in health problems with little variation and little task uncertainty, while many tasks are complex and uncertain. The participation of health care professionals in the development of quality indicators is, therefore, very important. PMID- 20356425 TI - [A woman with an abdominal mass]. AB - A 91-year-old woman had nausea, anorexia and diarrhoea and a large mass in her left upper abdomen due to a gastrointestinal stroma cell tumour of the stomach. PMID- 20356426 TI - [The process of bringing medication in line: the additional benefits of a Structured Medication History]. AB - OBJECTIVE: To determine the additional benefits of a structured history-taking of medication use (SHIM) from patients admitted to a geriatric ward for obtaining a complete and accurate list of medication used at home, in comparison to an unstructured medication history-taking by the resident physician. DESIGN: Prospective, observational. METHOD: The SHIM, a standardized questionnaire, was used for history-taking from patients admitted to the geriatric ward, and often from their caregivers, too. The number and type of discrepancies were noted between this medication history and the medication history obtained by the resident physician at admission as noted on the medical chart. Discrepancies were assessed for clinical relevance. RESULTS: The SHIM was used for 47 patients with a mean age of 84.4 years. At least one discrepancy was found in all patients. Comparison of the SHIM to the medication history obtained by the resident physician revealed 4.2 discrepancies per patient on average. Omission of medication in the history taken by the resident was the most common discrepancy. 66% of all discrepancies were considered as potentially clinically relevant; in 19% of the patients this actually resulted in a moderate degree of discomfort or clinical deterioration. The number of discrepancies was statistically significantly associated with the use of a higher number of medications and with the use of 'over the counter' (OTC) medications. CONCLUSION: The SHIM provides a better insight into the actual use of medication by the patient than history taking of medication use by the resident at admission. PMID- 20356427 TI - [Two infants with bleeding caused by alpha-1-antitrypsin deficiency]. AB - Alpha-1-antitrypsin deficiency (AATD) was diagnosed in a girl aged two months and a boy aged 18 days with neonatal cholestasis syndrome and vitamin K deficiency induced bleeding, including intracerebral bleeding. The differential diagnosis of neonatal cholestasis syndrome takes time, and treatable causes should be recognised as soon as possible. AATD is the most common hereditary cause of neonatal cholestasis syndrome. This autosomal recessive disorder is also associated with adult pulmonary emphysema. Diagnosis is simply made by determining the proteinase inhibitor (PI) phenotype with isoelectric focusing. No effective treatment is available. For patients with persistent liver disease liver transplantation may be necessary. PMID- 20356428 TI - [Haematological abnormalities in premature babies due to placental mesenchymal dysplasia]. AB - Two premature babies were admitted separately to the Neonatal Intensive Care Unit. One patient, a girl, presented with severe anaemia and thrombocytopaenia, the other, another girl, showed isolated thrombocytopaenia. During both pregnancies, ultrasound showed abnormalities of the placenta. The first patient also had intra-uterine growth restriction. A postpartum pathological examination showed abnormalities of both placentae consistent with placental mesenchymal dysplasia. Placental mesenchymal dysplasia is a rare condition which is associated with intra-uterine growth restriction, intra-uterine mortality, prematurity and Beckwith-Wiedemann syndrome. Thrombocytopaenia and anaemia are less commonly described in literature and are caused by micro-angiopathic haemolysis in the placenta. Both children had unrestricted growth and development patterns at one year and 6 months follow-up, respectively. PMID- 20356429 TI - ['Advanced triage' improves patient flow in the emergency department without affecting the quality of care]. AB - OBJECTIVE: To investigate whether 'advanced triage' improved patient flow among self-referred patients in the emergency department of a level 1 trauma centre and, most importantly, whether the quality of medical care was maintained. In advanced triage, the triage nurse initiates additional diagnostic investigations independently. DESIGN: Interventional study. METHODS: After a baseline measurement had been carried out for eleven days (n = 506), the advanced triage protocol was tested during ten day or evening shifts (n = 198). The length of stay in the emergency department was measured. The attending emergency physician assessed the correctness and completeness of the additional diagnostics initiated by the triage nurse. Two traumatologists and two radiologists assessed the quality of x-ray imaging requests independently of each other. RESULTS: Average patient length of stay (LOS) was reduced by fourteen minutes (14%). The improvement was achieved primarily in patients who required additional diagnostic investigations. Their average LOS decreased by 27 minutes (18%). There was an 8% increase in the total number of diagnostic investigations requested. The triage nurse initiated the investigations correctly and fully in 93% of cases. The quality of x-ray imaging requests remained the same as before the introduction of advanced triage. CONCLUSION: The implementation of advanced triage improved patient flow for self-referred patients in the emergency department without affecting the quality of medical care. Advanced triage was successful in the Dutch system, too. PMID- 20356430 TI - [Clinical cardiac rehabilitation]. AB - Outpatient cardiac rehabilitation (CR) is offered in at least 100 hospitals in the Netherlands. The majority of cardiac patients are well-served with physical training and education. Some patients with complex cardiac pathology and other problems, including health problems, may however benefit from multidisciplinary in-hospital CR. We present three cardiac patients. The first patient, a 58-year old man, had coronary and pulmonary disease, suboptimally treated diabetes and psychological problems. He participated in in-hospital CR for 7 weeks, which led to an improved physical and emotional condition. The second patient was 80 years old and did not recover properly following an aortic valve replacement. With in hospital CR she acquired new skills for mastering the activities of daily life. The third patient we described, a 57-year-old man, suffered from ischaemic heart failure and had had recurrent implantable cardiac defibrillator (ICD) shocks. He was referred for cardiac transplantation but 7 weeks of in-hospital CR resulted in an improved exercise tolerance, significant weight loss and an adequate level of coping with his disease. In-hospital CR is a niche service, but may provide relief for some cardiac patients. PMID- 20356431 TI - [How much water do we really need to drink?]. AB - Everywhere around us we see people sipping bottled water. In healthy people, the fluid balance is strictly regulated via osmoregulation by the hormone vasopressin and the kidneys, in combination with the thirst mechanism and drinking. Fluid intake comes from food, metabolism and beverages, including water. People lose fluid via the skin, respiration, faecal fluid and urinary output. The obligatory urine volume is determined by maximal renal concentrating ability and the solute load which must be excreted. Under normal circumstances of diet, exercise and climate the minimal urine output for healthy subjects is about 500 ml/day. Intake of more than 500 ml of fluids per day will result in the excretion of solute-free water. The recommended total daily fluid intake of 3,000 ml for men and of 2,200 ml for women is more than adequate. Higher fluid intake does not have any convincing health benefits, except perhaps in preventing (recurrent) kidney stones. PMID- 20356432 TI - [Work-related fatigue in highly-educated women older than 50]. AB - Recent findings by Verdonk et al. show that the prevalence of work-related fatigue among 47,000 Dutch employees is greatest in highly-educated women, aged 50-64 years. Although the study has several limitations, the findings are alarming, demand urgent measures and should be on the shortlist of policy makers, employers, and company doctors. Reduced time pressure and emotional demand at work, adequate support for women's ambitions, and proper consideration for the work-private life balance are needed. Coaching may help women to become more assertive and generate more job control. In addition, the problem of workplace violence must be adequately addressed. I am of the strong opinion that work related fatigue in women would significantly decrease if women were to occupy more leadership positions and top jobs. In such positions they would have greater autonomy and more opportunities to organise their work according to their own time schedules and insights. The time is ripe for women to be given a quota of top positions in the Netherlands. PMID- 20356433 TI - [A woman with an obstetric curiosity]. AB - A primipara underwent a caesarean section for preeclampsia. It so happened that vasa praevia were seen during the operation. A healthy boy was born. PMID- 20356434 TI - [Diagnosis and treatment of carcinoma of the gall bladder]. AB - Over the past decade considerable progress has been made in several fields relating to the diagnosis and treatment of gall bladder cancer. This literature search evaluates if these recent advances have led to improved diagnosis, treatment and survival of patients with gall bladder carcinoma. The increase in the number of cholecystectomies being carried out has resulted in more carcinomas being discovered incidentally, and at an early and treatable stage. The combination of ultrasound and MRI yields the most accurate preoperative staging. Current radiotherapy and chemotherapy in adjuvant and neoadjuvant settings have not shown any survival benefit. Surgical resection remains the only potentially curative option. For in-situ- and T1a-tumours a simple cholecystectomy can be performed resulting in favourable 10-year survival. For T1b- and T2-tumours an additional resection is indicated, resulting in 5-year survival rates of 55-90%. For T3-tumours, only those patients without metastatic disease will benefit from an additional resection. PMID- 20356435 TI - [A man with consolidation of the right lung]. AB - A 68-year-old man, who had been exposed to asbestos in the past, presented with pleural effusion and right lower lobe consolidation due to rounded atelectasis. PMID- 20356436 TI - [Implementation of the curriculum for specialist training in Emergency Medicine: room for improval on details]. AB - OBJECTIVE: To investigate what aspects of the new curriculum for specialist training in Emergency Medicine are actually implemented in daily practice. DESIGN: Descriptive study. METHOD: The curriculum was implemented as a pilot in 4 teaching hospitals, where a total of 32 residents in training in Emergency Medicine and 20 Emergency Medicine Program directors and Emergency physicians were surveyed using a web-based questionnaire querying the use of the different aspects of the curriculum in daily practice. RESULTS: Responses were received from 29 residents in training and 15 program directors and Emergency physicians. Both residents in training and program directors rated the patient mix seen during the training programme adequate to excellent. No great differences were observed in how residents in training, trainers and physicians working in the Emergency Department assessed the curriculum. However, the results showed that the training plan should be discussed explicitly with each residents in training. More attention should be focussed on the Society Awareness, Knowledge and Science and Organisation competencies and the Disability and Dermatology themes. Competence-based assessment methods, such as multi-source feedback, specific to this type of curriculum have not yet been sufficiently implemented. CONCLUSION: The responses to the questionnaire demonstrated how the curriculum is handled in daily practice and provided information on the progress of the implementation of the curriculum. This will enable focussed feedback to teaching hospitals. PMID- 20356438 TI - Health care utilization among adults aged 55-64 years: how has it changed over the past 10 years? AB - KEY FINDINGS: The percentage of physician office and hospital outpatient department (OPD) visits during which an MRI/CT/PET scan was ordered doubled, to 4%, and the percentage of hospital emergency department visits with an MRI/CT scan more than tripled, to 16%. The percentage of physician office and OPD visits with at least five drugs prescribed more than doubled, to 25%. Inpatient hospitalization rates were similar in 2006 and 1996, but the types of procedures and surgeries performed have changed. Hospitalization rates for coronary artery stent insertions, hip replacements, and knee replacements rose sharply, while rates for some other procedures declined. Ambulatory surgery visit rates were almost twice as high in 2006 as in 1994-1996, and for some types of ambulatory procedures, such as colonoscopies, the increase was even greater. PMID- 20356437 TI - Antidepressant imipramine induces human astrocytes to differentiate into cells with neuronal phenotype. AB - Several recent studies have expanded our conception of the role of astrocytes in neurogenesis, proposing that these cells may contribute to this phenomenon not only as a source of trophic substances, but also as stem cells themselves. We recently observed in vitro that human mature astrocytes can be induced to differentiate into cells with a neuronal phenotype. Antidepressant drugs have been shown to increase neurogenesis in the adult rodent hippocampus. In order to better understand the role of astroglia in antidepressant-induced neurogenesis, primary astrocyte cultures were treated with the antidepressant imipramine. Cell morphology was rapidly modified by treatment. In fact, whereas untreated astrocytes showed large, flat morphology, after a few hours of treatment cells exhibited a round-shaped cell body with long, thin processes. The expression of neuronal markers was analysed by immunocytochemistry, Western Blot and RT-PCR at different treatment times. Results showed an increase in neuronal markers such as neurofilament and neuron-specific enolase (NSE), whereas glial fibrillary acidic protein (GFAP) and nestin expression were not significantly modified by treatment. Similar results were obtained with fluoxetine and venlafaxine. Hes1 mRNA significantly increased after 2 h of treatment, suggesting involvement of this transcription factor in this process. These results confirm the role of astrocytes in neurogenesis and suggest that these cells may represent one of the targets of antidepressants. PMID- 20356439 TI - Establishment of the model of motorcyclist ejection injury. AB - OBJECTIVE: To establish the device and model of motorcyclist ejection injury. METHODS: Based on our laboratory devices, a motorcyclist ejection injury simulation system was developed. A total of 18 pigs were approved by the local animal experimentation and ethics committee to serve as the motorcyclist substitutes. In this ejection motion, the animal rode freely at the motor driver seat and was straightly accelerated by means of our custom motorcyclist ejection injury simulation system. When it was speeded up to the preset velocity (v equal to 30, 40 or 50 km/h) at the preset position, the animal was ejected forward. Pathological and dynamic analyses were conducted, accompanied with the high-speed photograph, acceleration/velocity signal test, gross observation and light microscope examination as well as the abbreviated injury score-injury severity score (AIS-ISS) scale. RESULTS: The high-speed photograph indicated that during the ejection procedure the motorcycle was first arrested and decelerated suddenly, and then the motorcycle driver was ejected forward, accompanied with the rotation motion in the air. Finally, the head, shoulder and thorax of the ejected animal impacted directly on the hard ground. Varying degrees of injury focusing on the liver, heart, lung and spleen were found. There existed a significant positive correlation between ISS and the ejection velocity of the motorcycle drivers (ISS equal to 16.7+/-2.9 for 30 km/h, 25.0+/-0.0 for 40 km/h and 37.3+/-1.0 for 50 km/h). The detailed injury characteristics were as follows: for the mildly injured animals, there were interlobar gaps or leaf gaps and lobar surface blood coagulation blocks in the liver, and mild lung hemorrhage; for the severely injured animals, there were liver comminuted laceration, moderate lung hemorrhage and heart injury. Animals suffering from the most severe injuries died half an hour later. CONCLUSION: The new injury model stated in this paper has a high stability and good repeatability, and is likely to be helpful to deeply investigate the injury mechanisms and protection countermeasures of motorcyclist ejection injury. PMID- 20356440 TI - Effect of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. AB - OBJECTIVE: To investigate the effect and clinical significance of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. METHODS: Thirty-three patients with severe trauma were randomly divided into a control group (n=16) and a treatment group (n=17). The patients of two groups were all treated conventionally, and the only difference was that Xuebijing injection was given to patients of the treatment group. The CD4+ and CD8+ subpopulations of T-lymphocyte in the peripheral blood were detected respectively on admission, 3rd and 5th days after trauma by double antibody labeling and flow cytometry. RESULTS: The CD4+ T-lymphocytes and CD4+/CD8+ ratio of peripheral blood in patients with severe trauma decreased markedly on the 3rd and 5th days after trauma. Furthermore, compared with control group, the peripheral CD4+ T-lymphocytes and CD4+/CD8+ ratio of treatment group renewed obviously on the 5th day after trauma, and showed statistical differences (P<0.05). CONCLUSION: In the treatment of patients with severe trauma, the early use of Xuebijing injection is effective in correcting disorder or suppression of T-lymphocyte subpopulations regulating network, and promoting a more balanced profile of immunologic function. PMID- 20356441 TI - Feasibility study on posterior laminar screw fixation techniques in the axis. AB - OBJECTIVE: To get morphologic parameters of Chinese adults through observation and measurement on axial laminas, to evaluate the feasibility of placing axial laminar screws and to introduce the technique. METHODS: Relative parameters of 28 sets of fresh Chinese adults'axial specimens, including distance from the superior and inferior entry points of axial laminar screws to the superior margins of axial laminas, superior, middle, inferior thickness and height of the axial laminas, length and angle of the axial laminar screw trajectories, distance from the entry points of axial laminar screws to the transverse foramen and central points of the inferior articular process, were measured with a digital caliper and a goniometer. Data were statistically analyzed. RESULTS: Averagely, distance from the superior and inferior entry points of axial laminar screws to the superior margins of axial laminas was 5 mm and 9 mm, superior, middle, inferior thickness and the height of the axial laminas were 3.2 mm, 6.7 mm, 5.5 mm and 12.8 mm respectively, and the length of the superior and inferior axial laminar screw trajectories was 26.2 mm and 25.5 mm, respectively. CONCLUSIONS: It is feasible and reliable to apply posterior laminar screw fixation techniques to the axes of Chinese adults. Also the C2 laminar screw fixation technique can be taken as a supplementary to conventional posterior screw fixations of C2. PMID- 20356442 TI - Medial approach for popliteal artery injuries. AB - OBJECTIVE: To evaluate the clinical application of the medial approach for repairing popliteal artery injuries. METHODS: From 2002 to 2008, 11 cases of popliteal artery injuries had been repaired via the medial approach. Of these cases, 8 had limb fractures, 1 had knee dislocation, and 2 had visceral injuries. Ten popliteal arteries were anastomosed directly while one was repaired with a great saphenous vein graft. RESULTS: The operation time ranged from 3 to 4 hours (averaging 3.6 hours). All the injured limbs survived. At the follow up, 8 legs recovered the full function, 2 had minor contracture, and 1 serious Volkmann's contracture without amputation. CONCLUSION: The medial approach for repair of the popliteal artery is effective, applicable, and more advantageous to the management of multi-injures. PMID- 20356443 TI - Civilian casualties of Iranian cities by ballistic missile attacks during the Iraq-Iran war (1980-1988). AB - OBJECTIVE: To determine the nature and extent of Iranian casualties by ballistic missile attacks during the eight years of the Iraq-Iran war. METHODS: The data collected about Iraqi missile strikes on Iranian cities included the following: date and time, number and type of missiles, cities targeted, and injuries and deaths resulting from impacts of missiles in civilian areas. The data were extracted from a database that was constructed by the army staff headquarters based on daily reports of Iranian army units during the war. RESULTS: Over a period of eight years (1980-1988), Iraqi army fired 533 ballistic missiles at Iranian territories. From those, 414 missiles (77.7%) landed on Iranian cities. The impacts of these missiles caused the deaths of 2,312 civilians and injured 11,625 others. Three types of ballistic missiles were used: FROG-7, Scud, and Al Hussein (a modified version of the Scud missile). Twenty-seven cities in Iran were struck by Iraqi ballistic missiles. The highest mortalities from ballistic missiles were in Dezful and Tehran. Iraqi missile attacks continued for 90 months (2,748 days). CONCLUSION: Our results point to the necessity of investigating the psychological consequences of Iraqi ballistic missile attacks among survivors in 27 Iranian cities during the eight years of the Iraq-Iran war. PMID- 20356444 TI - Chitosan green tea polyphenol complex as a released control compound for wound healing. AB - OBJECTIVE: In recent years, oxidative stress has been implicated in a variety of degenerative process and diseases, including acute and chronic inflammatory conditions such as wound healing. Green tea polyphenols have shown anti-oxidant property. The present study discussed the application of chitosan green tea polyphenol complex on the wound healing. METHODS: The wound healing effect of chitosan green tea polyphenol complex was studied in ten-week-old healthy male Sherman rats weighing 150-180 g by two wound models. The rats were randomly chosen and divided into four groups (n=5), administered with distilled water in Group A as control group, epigallocatechin-3-gallate (EGCG) in Group B, chitosan EGCG complex in Group C and chitosan-green tea polyphenols complex in Group D, respectively. In rats'incision wound model, two straight paravertebral incisions were made and skin tensile strength was measured using continuous water flow technology on the 10th day. In rats'excision wound model, wound contraction and period of epithelization were measured. The polyphenols release from the complex was continuously monitored by an elution technique in aqueous solution at different pH values (pH=4, 5, 6, 7). RESULTS: The treatment groups showed significantly enhanced the breaking strength in incision wound (328+/-14.5) g and (421+/-18.5) g compared with control (264+/-16.7) g. In the excision wound model, the wound contraction percentage in treatment groups was relatively increased during the recovery period. Respectively, the percentage of wound contraction ranged from 47.60%+/-2.15% on day 4 to 107.98% +/-1.26% on day 16 compared with control group (8.46%+/-5.42% to 59.80%+/-4.47%). The complex demonstrated a gradual increase in the release rate from the initial stage and slow increase at different pH values. The release rate approximated 0.6-0.7 in the complex and remained stable 6 hours after injury, which may be the end of the release process. CONCLUSIONS: In our study, chitosan polyphenol complex has enhanced the healing of incision wounds by increasing the breaking strength of the wounds. In excision wound model, the complex hastens the period of epithelialization. The study on the optimal release of complex among various pH values could be applied in the wound test, which can lead to a gradually active substance(polyphenols) release and efficient coverage of epithelial layers found in the healing of incision and excision wound. PMID- 20356445 TI - Treatment of Gustilo grade III leg fractures by external fixation associated with limited internal fixation. AB - OBJECTIVE: To explore the clinical effects of external fixation associated with limited internal fixation on treatment of Gustilo grade III leg fractures. METHODS: From July 2006 to December 2008, 40 cases of Gustilo grade III leg fractures were emergently treated in our unit with external fixation frames. Soft tissue injuries were grouped according to the Gustilo classification as IIIA in 17 cases, IIIB in 13 cases, and IIIC in 10 cases. All the patients were debrided within 8 hours, and then fracture reposition was preformed to reestablish the leg alignment. Limited internal fixation with plates and screws were performed on all the Gustilo IIIA cases and 10 Gustilo IIIB cases at the first operation. But all the Gustilo IIIC cases and 3 Gustilo IIIB cases who had severe soft tissue injuries and bone loss only received Vacuum-sealing drainage (VSD). Broad spectrum antibiotics were regularly used and VSD must be especially maintained easy and smooth for one week or more after operation. Limited internal fixation and transplanted free skin flaps or adjacent musculocutaneous flaps were not used to close wounds until the conditions of the wounds had been improved. RESULTS: The first operations were completed within 90-210 minutes (170 minutes on average). The blood transfusions were from 400 ml to 1500 ml (those used for anti shock preoperatively not included). All the 40 patients in this study were followed up for 6-28 months, 20.5 months on average. The lower limb function was evaluated according to the comprehensive evaluation standards of leg function one year after operation and the results of 28 cases were excellent, 9 were good and 3 were poor. CONCLUSION: External fixation associated with limited internal fixation to treat Gustilo grade III leg fractures can get satisfactory early clinical therapeutic effects. PMID- 20356446 TI - Epidemiological investigation on Wenchuan earthquake-struck trauma patients admitted to two hospitals of Chongqing. AB - OBJECTIVE: To study epidemiological characteristics and influential factors of in hospital patients struck by the Wenchuan earthquake disaster. METHODS: The clinical data of 196 cases were collected from 2 hospitals of Chongqing city, including age, sex, occupation, injury site, dwelling and injury severity score. RESULTS: In this series, 31.63% victims'age was over 60 years, and 54.08% were farmers. Multiple trauma accounted for 35.71%, and lower limb injury for 33.67%. There was no significant difference on injury severity score between city dwellers and rural ones (P>0.05). CONCLUSION: The earthquake injury is influenced by many factors. More attention should be paid to the treatment at first 5 days after injury and high risk population. PMID- 20356447 TI - Aquaporin-4 and traumatic brain edema. AB - Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema. PMID- 20356448 TI - Circulating fibrocytes: a potent cell population in antigen-presenting and wound healing. AB - Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase. Moreover, they can promote the endothelial cell proliferation, migration and angiogenesis by secreting several proteins. Fibrocytes can further differentiate into mature mesenchymocyte lineage, such as fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds. A deep understanding of the mechanism involved in fibrocyte migration and differentiation may lead to the development of a novel theory of normal physiology and pathology. PMID- 20356449 TI - Upper limb compartment syndrome after an adder bite: a case report. AB - Compartment syndrome after an adder bite is extremely rare, whose effects are only secondary to the cytotoxic and hemorrhagic effects of venom. Here we reported a case of compartment syndrome in the upper limb following an adder bite in the thenar eminence. Elevated compartment pressure was documented and immediate surgical fasciotomy was practiced. The patient achieved complete recovery with a good functional result. We discussed the controversies on fasciotomy and non-invasive measures in such a situation, and recommended intracompartmental pressure monitoring during the management of compartment syndrome following adder bites. PMID- 20356450 TI - A 92-year-old man with retropharyngeal hematoma caused by an injury of the anterior longitudinal ligament. AB - Traumatic retropharyngeal hematoma is a rare condition and may be lethal in some cases. In patients with this condition, the absence of a vertebral fracture or a major vascular injury is extremely rare. We present the case of a 92-year-old man who hit his forehead by slipping on the floor in his house. He had no symptoms at the time; however, he experienced throat pain and dyspnea at 6 hours after the injury. On arrival, he complained of severe dyspnea; therefore, an emergency endotracheal intubation was performed. A lateral neck roentgenogram after intubation showed dilatation of the retropharyngeal and retrotracheal space and no evidence of a cervical vertebral fracture. Cervical computed tomography (CT) with contrast medium revealed a massive hematoma extending from the retropharyngeal to the superior mediastinal space but no evidence of contrast medium extravasation or a vertebral fracture. However, sagittal magnetic resonance imaging (MRI) revealed an anterior longitudinal ligament (C4-5 levels) injury. We determined that the cause of the hematoma was an anterior longitudinal ligament injury and a minor vascular injury around the injured ligament. Therefore, we recommend that patients with retropharyngeal hematoma undergo sagittal cervical MRI when roentgenography and CT reveal no evidence of injury. PMID- 20356451 TI - Is early hardware removal compulsory after retention of angled drill guides in palmar locking plates? The role of pronator quadratus reconstruction. AB - Palmar plate fixation is becoming a well recognized treatment for distal radial fracture. Tendon ruptures or irritations have been reported after this procedure. Inadvertent retention of angled drill guides useful for easy placement of locking screws in proper direction in volar plating can represent a high risk of secondary tendon rupture. In this case, we presented our experience in one patient in whom drill guides removal could be delayed for one year and summarized our techniques to prevent the aforementioned complications. PMID- 20356452 TI - Traumatic bilateral hip dislocation with bilateral sciatic nerve palsy. AB - Bilateral hip dislocation rarely occurs. In this paper, a case of bilateral hip dislocation associated with bilateral sciatic nerve palsy resulted from a road traffic accident is reported. Both hips were emergently reduced under general anaesthesia. Acetabular reconstruction was done bilaterally due to the unstable hips. The patient subsequently developed heterotopic ossification and avascular necrosis on the left hip and underwent total hip arthroplasty. The sciatic nerve on the right side achieved complete recovery but that on the left side only partly recovered and was augmented by tendon transfer. Such injuries are serious and one should be aware of the complications because they can resurface and so patients should be followed up for a long time. To the best of our knowledge, this kind of injury has not been reported in the English language literature. PMID- 20356453 TI - Membrane associated Ca2+ buffers in the heart. AB - Ca2+ is a universal signalling molecule that affects a variety of cellular processes including cardiac development. The majority of intracellular Ca2+ is stored in the endoplasmic and sarcoplasmic reticulum of muscle and non-muscle cells. Calreticulin is a well studied Ca2+-buffering protein in the endoplasmic reticulum, and calreticulin deficiency is embryonic lethal due to impaired cardiac development. Despite calsequestrin being the most abundant Ca2+-buffering protein in the sarcoplasmic reticulum, viability is maintained in embryos without calsequestrin and normal Ca2+ release and contractile function is observed. The Ca2+ homeostasis regulated by the endoplasmic and sarcoplasmic reticulum is critical for the development and proper function of the heart. PMID- 20356454 TI - Characterization of calumenin in mouse heart. AB - Calumenin is a multiple EF-hand Ca2+-binding protein located in the endo/sarcoplasmic reticulum of mammalian hearts. Calumenin belongs to the CREC family of Ca2+-binding proteins having multiple EF-hands. Ca2+ homeostasis in the sarcoplasmic reticulum (SR) of mammalian hearts is maintained by RyR2, SERCA2 and other associated SR resident proteins. Evidence suggests that calumenin interacts with RyR2 and SERCA2, and therefore changes in the expression of calumenin could alter Ca2+ cycling in mouse heart. In this review, current knowledge of the biochemical and functional roles of calumenin in mouse heart is described. PMID- 20356455 TI - The production and immunostimulatory activity of double-stranded CpG-DNA. AB - CpG-DNA, which contains unmethylated CpG dinucleotides in the context of specific sequences, has remarkable and diverse immunological effects, including induction of proinflammatory cytokine expression and regulation of the Th1/Th2 immune response. Here, we examined the immunostimulatory activities of double-stranded (ds) CpG-DNA in the human B cell line RPMI8226. To investigate whether dsCpG-DNA stimulates immune cells, we constructed a plasmid containing repeated dsCpG-DNA and produced dsCpG-DNA by PCR amplification and EcoR I digestion. PCR-amplified dsCpG-DNA alone did not have immmunostimulatory activity. However, dsCpGDNA encapsulated with lipofectin induced IL-8 promoter activation, HLA-DRA expression, and IL-8 expression in a CG sequence- independent manner. The effects of encapsulated dsCpGDNA were independent of minor endotoxin contamination. These findings suggest the potential use of dsCpG-DNA as a therapy for immune response regulation. PMID- 20356456 TI - Distinct functional roles of peroxiredoxin isozymes and glutathione peroxidase from fission yeast, Schizosaccharomyces pombe. AB - To investigate the differences in the functional roles of peroxiredoxins (Prxs) and glutathione peroxidase (GPx) of Schizosaccharomyces pombe, we examined the peroxidase and molecular chaperone properties of the recombinant proteins. TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction with the thioredoxin system. GPx also showed thioreoxin-dependent peroxidase activity rather than GPx activity. The peroxidase activity of BCP (bacterioferritin comigratory protein) was similar to that of TPx. However, peroxidase activity was not observed for PMP20 (peroxisomal membrane protein 20). TPx, PMP20, and GPx inhibited thermal aggregation of citrate synthase at 43(o)C, but BCP failed to inhibit the aggregation. The chaperone activities of PMP20 and GPx were weaker than that of TPx. The peroxidase and chaperone properties of TPx, BCP, and GPx of the fission yeast are similar to those of Saccharomyces cerevisiae. The fission yeast PMP20 without thioredoxin-dependent peroxidase activity may act as a molecular chaperone. PMID- 20356457 TI - Stabilization of the primary sigma factor of Staphylococcus aureus by core RNA polymerase. AB - The primary sigma factor (sigma(A)) of Staphylococcus aureus, a potential drug target, was little investigated at the structural level. Using an N-terminal histidine-tagged sigma(A) (His-sigma(A)), here we have demonstrated that it exits as a monomer in solution, possesses multiple domains, harbors primarily alpha helix and efficiently binds to a S. aureus promoter DNA in the presence of core RNA polymerase. While both N- and C-terminal ends of His- sigma(A) are flexible in nature, two Trp residues in its DNA binding region are buried. Upon increasing the incubation temperature from 25 degrees to 40 degrees C, 60% of the input His sigma(A) was cleaved by thermolysin. Aggregation of His-sigma(A) was also initiated rapidly at 45( degrees )C. From the equilibrium unfolding experiment, the Gibbs free energy of stabilization of His-sigma(A) was estimated to be +0.70 kcal mol(-1). The data together suggest that primary sigma factor of S. aureus is an unstable protein. Core RNA polymerase however stabilized sigma(A) appreciably. PMID- 20356458 TI - CMTM5-v1, a four-transmembrane protein, presents a secreted form released via a vesicle-mediated secretory pathway. AB - The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking classical chemokines and the transmembrane 4 superfamily (TM4SF). Our earlier studies indicated several CMTM members (such as CKLF1 and CMTM2) have a secreted form. This is the first report of the secreted form of CMTM5-v1, the major RNA splicing form of CMTM5, which is produced as small vesicles (100 nm diameter) and floats at a peak density of 1.19 g/ml on continuous sucrose gradients. CMTM5-v1 has no obvious co-localization with CD63 or Golgi complex. In addition, brefeldin A but not wortmannin can inhibit the secretion of CMTM5-v1. Our results suggest that CMTM5-v1 might be secreted via a different vesicle-mediated secretory pathway, which will be helpful for the studies of vesicle-mediated secretion and MARVEL domain-containing proteins. PMID- 20356459 TI - Effect of atorvastatin on dendritic cells of tubulointerstitium in diabetic rats. AB - Inflammatory reactology has become increasingly important in diabetic kidney disease. In this study, we estabilished STZ-induced diabetic rat model to investigate whether dendritic cells (DCs) mediated tubulointerstitial damages, and whether the effects by DCs were mediated by P-selectin expression and can be inhibited by atorvastatin. The study demonstrated that there was an accumulation of DCs in diabetic rats mediated by P-selectin. It also showed the accumulation of DCs and expression of P-selectin was closely correlated with the degree of renal tubulointerstitial injury. These effects were markedly attenuated by atorvastatin. Thus, DCs play a role in tubulointerstitial damages, atorvasttin can prevent renal tubulointerstitium from damage by inhibiting the P-selectin expression and DCs migration. PMID- 20356460 TI - ZNF552, a novel human KRAB/C2H2 zinc finger protein, inhibits AP-1- and SRE mediated transcriptional activity. AB - In this study, we report the identification and characterization of a novel C2H2 zinc finger protein, ZNF552, from a human embryonic heart cDNA library. ZNF552 is composed of three exons and two introns and maps to chromosome 19q13.43. The cDNA of ZNF552 is 2.3 kb, encoding 407 amino acids with an amino-terminal KRAB domain and seven carboxyl-terminal C2H2 zinc finger motifs in the nucleus and cytoplasm. Northern blotting analysis indicated that a 2.3 kb transcript specific for ZNF552 was expressed in liver, lung, spleen, testis and kidney, especially with a higher level in the lung and testis in human adult tissues. Reporter gene assays showed that ZNF552 was a transcriptional repressor, and overexpression of ZNF552 in the COS-7 cells inhibited the transcriptional activities of AP-1 and SRE, which could be relieved through RNAi analysis. Deletion studies showed that the KRAB domain of ZNF552 may be involved in this inhibition. PMID- 20356461 TI - Novel p104 protein regulates cell proliferation through PI3K inhibition and p27(Kip1) expression. AB - The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase Cgamma1, and has been shown to associate with p85alpha, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich region of p104. The proline-rich region of p104 has been found to inhibit the colony formation of platelet-derived growth factor BB-stimulated NIH3T3 cells and MCF7 cancer cells on soft agar. Mutagenesis analysis showed that the second and third proline-rich regions are essential for growth control, as well as for interaction with p85alpha. Overexpression of p104 increased the level of the cyclin-dependent kinase inhibitor, p27(Kip1), and inhibited the activity of phosphoinositide 3 kinase (PI3K). In summary, p104 interacts with p85alpha and is involved in the regulation of p27(Kip1) expression for the reduction of cellular proliferation. PMID- 20356462 TI - Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts. AB - Sprouty (Spry) proteins have previously been suggested as negative regulators of the MAPK pathway through interaction with Raf-1. However, the molecular basis of this inhibition has not been elucidated. In this study, we used cells expressing FLAGtagged Raf-1 with point mutations at known phosphorylation sites to reveal that activation of Raf-1 mutants does not correlate with their degree of interaction with Spry2. The association of Raf-1 with Spry2 in intact cells was further corroborated by immunofluorescence colocalization. Additionally, there was no significant change observed in the strength of interaction between Raf-1 mutants and Spry2 after paclitaxel treatment despite differences in the activation levels of these mutants. Thus, our study provides the evidence that Spry2 does not directly regulate Raf-1 kinase activity, but instead acts as a scaffolding protein that assists interactions between Raf-1 kinase and its direct regulators. PMID- 20356463 TI - ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway. AB - Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK- 293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions. PMID- 20356464 TI - Reaction of ferritin with hydrogen peroxide induces lipid peroxidation. AB - Lipid peroxidation is known to be an important factor in the pathologies of many diseases associated with oxidative stress. We assessed the lipid peroxidation induced by the reaction of ferritin with H2O2. When linoleic acid micelles or phosphatidyl choline liposomes were incubated with ferritin and H2O2, lipid peroxidation increased in the presence of ferritin and H2O2 in a concentration dependent manner. The hydroxyl radical scavengers, azide and thiourea, prevented lipid peroxidation induced by the ferritin/H2O2 system. The iron specific chelator desferoxamine also prevented ferritin/H2O2 systemmediated lipid peroxidation. These results demonstrate the possible role of iron in ferritin/H2O2 system-mediated lipid peroxidation. Carnosine is involved in many cellular defense processes, including free radical detoxification. In this study, carnosine, homocarnosine, and anserine were shown to significantly prevent ferritin/H2O2 system-mediated lipid peroxidation and also inhibited the free radical-generation activity of ferritin. These results indicated that carnosine and related compounds may prevent ferritin/H2O2 system-mediated lipid peroxidation via free radical scavenging. PMID- 20356465 TI - Dioxin-like activity in the blood of Greenlandic Inuit and Danish women: a pilot study. AB - OBJECTIVES: (1) To determine whether plasma dioxin-like (DL) bioactivity differs between Inuit living in different Greenlandic districts, (2) to compare the DL activity of the Inuit having high burdens of POPs with a low-burden study group (Danish volunteers), and (3) to evaluate DL activity associations to POP exposure biomarkers and/or lifestyle factors. STUDY DESIGN: The study was a cross sectional survey, including randomized inhabitants (70) from 6 different Greenlandic districts and young Danish volunteers (22). METHODS: POPs and fatty acids profiles were analysed. Aryl hydrocarbon receptor (AhR) mediated DL activity was determined by exposure of Hepa1.12cR AhR-CALUX reporter cell line to hexane: ethanol plasma extracts. RESULTS: The sum PCBs/POPs level of Inuit was more than 10 times higher than the levels found in Danish volunteers, and for both study groups the level was positively associated with age. The TCDD equivalent of the determined DL-activity, AhR-TEQ, differed between the Greenlandic districts. The AhR-TEQ data of the combined Inuit was significantly higher compared with the Danish women. AhR-TEQ of Inuit were positively associated with plasma POPs after adjustment for age and/or the ratio of n-3 to n 6 fatty acids, whereas no correlations were found for the Danish samples. CONCLUSIONS: AhR-TEQ differs between Inuit and Danish plasma samples. Plasma POP levels alone cannot be used as a biomarker for DL-activity. We suggest that the profile and level of plasma POPs, geographical location and diet have the greatest impact on plasma dioxin activity. Further studies are needed to elucidate the differences in geographical determinants of blood DL-activity. PMID- 20356466 TI - Emerging obesity among preschool-aged Canadian Inuit children: results from the Nunavut Inuit Child Health Survey. AB - OBJECTIVES: The study goal was to evaluate the growth status of preschool-age Canadian Inuit children. STUDY DESIGN: As part of a larger study of population health across the Canadian High Arctic, the International Polar Year Inuit Health Survey collected growth and nutrition data on 388 children aged 3 to 5 years. METHODS: Data collection included anthropometric measures, health history, food frequency and 24-hour recall. Height and BMI were compared with the 2000 Centers for Disease Control and Prevention (CDC) growth reference (1); 24-hour recall and FFQ results were tabulated to produce daily and monthly frequencies of consumption of market and country foods. RESULTS: Mean height-for-age z-scores were comparable, but body mass index z-scores were significantly greater than the U.S. standard reference population for all age and sex categories. The overall prevalence of overweight was 50.8%. There were significantly more boys (57.1%) than girls (45.2%) in the overweight category. An examination of biological, socio-economic and dietary factors, including birth weight, breastfeeding, day care attendance, traditional and market food consumption and sweetened beverage consumption revealed no significant associations that could explain the development of obesity risk in this population. CONCLUSIONS: Stature in preschool age Inuit children is comparable to the U.S. reference, indicating that the previously reported secular trend toward increasing height has continued. Overweight prevalence is higher than that previously reported in Inuit children and may be occurring at an earlier age. The gender difference in child overweight prevalence runs counter to that reported in adults, leading to concern that contemporary growth atterns may result in significant increases in obesity related illness for young Inuit men. PMID- 20356467 TI - The health of Canada's Aboriginal children: results from the First Nations and Inuit Regional Health Survey. AB - OBJECTIVES: Reports on child health in Canada often refer to the disproportionate burden of poor health experienced by Aboriginal children and youth, yet little national data are available. This paper describes the health of First Nations and Inuit children and youth based on the First Nations and Inuit Regional Health Survey (FNIRHS). STUDY DESIGN: The FNIRHS combines data from 9 regional surveys conducted in 1996-1997 in Aboriginal reserve communities in all provinces. The target population consisted of all on-reserve communities. All households or a random sample of households or adults (depending on province) were selected based on their population representation. METHODS: One child was randomly selected from each participating household, except in Ontario and Nova Scotia, where children were randomly selected based upon their population representation. Alberta did not include the section on children's health in their regional survey. RESULTS: Approximately 84% of adults, who were proxy respondents for their child, rated their children's health as very good or excellent. The most frequently reported conditions were ear problems (15%), followed by allergies (13%) and asthma (12%). Broken bones or fractures were the most frequently reported injuries (13%). Respondents reported that 17% of children had behavioural or emotional problems. Overall, 76% of children were reported to get along with the family "very well" or "quite well." CONCLUSIONS: While most respondents rated their child's health as very good or excellent, injuries, emotional and behavioural problems, respiratory conditions and ear problems were reported among many Aboriginal children. Issues such as substance abuse, exposure to violence and academic performance were not addressed in the 10 core survey questions. Clearly there is a need for more in-depth information about both the physical and emotional health of Aboriginal children and youth. PMID- 20356468 TI - The relationship between socio-economic and geographic factors and asthma among Canada's Aboriginal populations. AB - OBJECTIVES: To examine the prevalence, exacerbations and management of asthma among Canada's Aboriginal populations, and its relationship to socio-economic and geographic factors. STUDY DESIGN: Secondary analysis of a national cross sectional questionnaire survey. METHODS: Data were collected in 2000 and 2001 through a survey of Aboriginal children and adults residing on- and off-reserve as part of the 2001 Aboriginal People's Survey (APS). The asthma related outcome variables - physician-diagnosed asthma, attack in past year and regular use of inhalants - were examined in relation to socio-economic and geographic factors such as income, education, housing and location of residence. Statistical analyses were based on weighted univariate and multivariate logistic regressions. RESULTS: The results show variations in asthma diagnosis, attacks and inhalant use across geographic location, socio-economic and demographic characteristics. Geographic location was found to be significantly associated with asthma for both adults and children, with those living in the northern territories, on-reserve or rural locations being the least likely to be diagnosed. Geographic location and Aboriginal identity were also found to be significantly associated with asthma medication use. CONCLUSIONS: While these findings may suggest a "healthier" population in more remote locations, they alternatively point to a general pattern of under-diagnosis, potentially due to poor health care access, as is typical in more remote locations. PMID- 20356469 TI - Unnatural deaths in reindeer-herding Sami families in Sweden, 1961-2001. AB - OBJECTIVES: Unnatural deaths among Indigenous populations, including the Swedish Sami, occur more often than among the general population. To find prevention strategies, we explored the circumstances of the unnatural deaths of members of reindeer-herding Sami families. STUDY DESIGN: The number of deaths from among a cohort of 7,482 members of reindeer-herding Sami families were retrieved from the National Board of Health and Welfare for the years 1961- 2001. METHODS: An evaluation of the information from autopsy records at the National Board of Forensic Medicine, police reports, and available medical records identified 158 unnatural deaths. These were then analysed in detail. RESULTS: Transport-related deaths and suicides were the most common unnatural deaths among Swedish reindeer herding Sami family members. Suicides contributed to 23% of all deaths, road traffic accidents to 16%, and snowmobile fatalities to 11%. The accidents generally reflected an "outdoor lifestyle" and the working conditions were characterized by the use of off-road vehicles such as snowmobiles. Half of the number of victims tested positive for alcohol and alcohol abuse was documented in 15% of all victims. CONCLUSIONS: The results indicate that alcohol is an important factor in preventing unnatural deaths among reindeer-herding Sami, together with increased safety of both on-road and off-road transportation. PMID- 20356470 TI - [Early intensive insulin therapy in newly diagnosed type 2 diabetes: the size of the problem.]. PMID- 20356471 TI - [The crosstalk between skeletal and cardiovascular system: focusing on the impact of bone metabolism on blood pressure.]. PMID- 20356472 TI - [The appropriat interpretation and practice of informations from randomized clinical trials.]. PMID- 20356473 TI - [The effects of early intensive therapy on islet beta cell function and long-term glycemia control in newly diagnosed type 2 diabetic patients with different fasting plasma glucose levels.]. AB - OBJECTIVE: To investigate the effects of early intensive therapy on beta cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels. METHODS: A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0 - 16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia. The treatments were stopped after euglycemia had been maintained for 2 weeks. The patients were followed longitudinally on diet alone for 1 year. Intravenous glucose tolerances tests (IVGTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up. Homeostasis model assessment (HOMA) of beta cell function and insulin resistance index (HOMA-beta and HOMA-IR) were calculated. All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L 0.05). The rates of combination therapy were both 54% in the two groups. (2) Fasting insulin as well as 30 min and 120 min insulin levels after oral glucose tolerance test and insulin area under the curve in the metformin group were significantly reduced after 4 and 8 weeks of treatment as compared with those of baseline (P < 0.05 and P < 0.01). In the fosinopril group, however, they decreased only after 8 weeks treatment (P < 0.05). The insulin action index in the metformin group was higher than that in the fosinopril group after 4 weeks of treatment (P < 0.05), but there was no significant difference between the two groups after 8 weeks of treatment (P > 0.05). CONCLUSION: Metformin and fosinopril have similar antihypertensive effect and a good synergy in essential hypertension with hyperinsulinemia. PMID- 20356475 TI - [Evaluation of the impact of genetic background on islet beta-cell function of normal glucose tolerance and newly diagnosed diabetic patients by L-arginine stimulation test.]. AB - OBJECTIVE: To explore the impact of genetic background on pancreatic beta-cell first-phase secretion function with L-arginine (L-ARG) stimulation test. METHODS: Plasma insulin level was detected in 201 cases before and after L-ARG stimulation test. Among them, 61 cases were newly diagnosed type 2 diabetic patients with family history of diabetes (FH+DM), 55 newly diagnosed type 2 diabetic patients without family history of diabetes (FH-DM), 31 with normal glucose tolerance and family history of diabetes (FH+) 54 with normal glucose tolerance but without family history of diabetes (FH-). Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR). RESULTS: It was premised that gender, age and BMI were similar among the 4 groups. (1) TC, TG, fasting plasma glucose, 2h plasma glucose, fasting insulin and HOMA-IR in the two groups of newly diagnosed type 2 diabetic patients with or without family history of diabetes were significantly higher than those in the two groups of normal glucose tolerance with or without family history of diabetes. The multiples of the peak level and the base level of insulin secretion in the groups of newly diagnosed diabetes were significantly lower than those in the groups of normal glucose tolerance with and without family history (P < 0.05). (2) Insulin secretion reached a peak in 2 minutes and started to decline in 4 minutes in all the four groups. (3) The multiples of the peak level and the base level of insulin secretion in normal glucose tolerance group with family history of diabetes were 20.8% lower than those in the group without family history, being 7.27 and 9.18 respectively (P < 0.05). (4) Two-minute peak insulin secretion, HOMA-IR and age in the newly diagnosed type 2 diabetic group with family history of diabetes was significantly lower than these in the group without family history (P < 0.05). The multiples of the peak level and the base level of insulin secretion in the newly diagnosed type 2 diabetic group with family history of diabetes and that group without family history were 5.18 and 5.31 respectively and there was no significant difference between the two groups (P > 0.05). (5) When the normal glucose tolerance subjects with family history of diabetes progressed to suffer from diabetes, the multiples of the peak level and the base level of insulin secretion declined 43.6% (P < 0.05) more than those in the subjects still with normal glucose tolerance without family history. CONCLUSION: In the early course of diabetes, insulin resistance dose not function significantly, but genetic background make the first-phase secretory function of the beta-cell to decline gradually and type 2 diabetes occurs easily. In the absence of genetic background, insulin resistance makes first-phase the secretion of insulin to decline relatively slow. PMID- 20356476 TI - [Renal insufficiency and its associated factors in type 2 diabetic patients with normoalbuminuria.]. AB - OBJECTIVE: To investigate the prevalence of renal insufficiency and its associated factors in type 2 diabetes mellitus with normoalbuminuria using estimated glomerular filtration rate (eGFR). METHODS: We retrospectively analyzed 10-year data of chronic complications in type 2 diabetics in-patient from the Chinese Diabetes Society. eGFR was estimated using the equation from Modification of Diet in Renal Disease (MDRD) study. The clinical characteristics as well as associated factors for low eGFR were analyzed among the normoalbuminuric type 2 diabetic patients. RESULTS: A total of 1351 type 2 diabetic patients were included, 755 patients with normoalbuminuria, 466 patients with microalbuminuria and 130 patients with macroalbuminuria respectively. Among the patients, 310 (22.9%) had low eGFR (GFR < 60 mlxmin(-1) x 1.73 m(-2)), 19.7% (149/755) in the patients with normoalbuminuria, 21.9% (102/466) in microalbuminuria and 45.4% (59/130) in macroalbuminuria. Patients with normoalbuminuria and low eGFR suffered more chronic complications than those with normoalbuminuria and normal eGFR, mainly retinopathy, cerebrovascular diseases and sensory neuropathy. Stepwise logistic regression analysis revealed that age (OR = 1.042, P < 0.001), diabetic duration (OR = 1.038, P = 0.045), systolic blood pressure (OR = 1.017, P < 0.001) were independently associated with renal impairment among the patients with normoalbuminuria. Body mass index (OR = 0.868, P < 0.001) and HbA1c (OR = 0.898, P = 0.021) were also related with renal insufficiency. CONCLUSION: A considerable proportion in type 2 diabetic patients without albuminuria may exist renal impairment, and eGFR estimation could benefit the evaluation of renal function in such patients. PMID- 20356477 TI - [Effects of aging and decreased glomerular filtration rate on the prevalence of anemia in elderly population receiving body check from urban area of Hefei, China.]. AB - OBJECTIVE: To investigate the effects of aging and the decreased glomerular filtration rate on the prevalence of anemia in elder receiving body check from urban area of Hefei, China. METHODS: A total of 4547 > 60 years subjects received healthy examination in Healthy Center of Anhui Provincial Hospital from January 2005 to December 2007 were enrolled in this study. Anemia was defined as hemoglobin < 120 g/L in men or < 110 g/L in women. RESULTS: The prevalence of anemia in the subjects was 4.40% (95%CI: 3.83% - 5.05%) and significantly increased with the aging process and the decline of estimated glomerular filtration rate (eGFR). With logistic analyses, increasing age, female, decreased eGFR were major risk factors for anemia. CONCLUSIONS: The morbidity of anemia is 4.40% in old population receiving body check from urban area of Hefei, China. Aging and the decline of eGFR are the independent risk factors of anemia. PMID- 20356478 TI - [The smoking status of patients with acute coronary syndrome and effect of simple intervention on smoking cessation.]. AB - OBJECTIVE: To evaluate the abstinence rate and relapse rate of smoker with ACS after discharged from hospital, to evaluate the effect of simple smoking cessation interventions. METHODS: 150 smokers with ACS were collected and was divided into simple intervention group (n = 87) and control group (n = 63), respectively, followed up for 6 months. 2 months, 6 months abstinence rate, relapse rate were compared between two groups, logistic regression model was used to analyzed the relevant factors for relapse. RESULTS: The smoking rate in patients with ACS was 31.14%, 6-month continuous abstinence rate and 6-month relapse rate was 64.6%, 36.4%, respectively. 6-month continuous abstinence rate and relapse rate between simple quit-smoking intervention group and control group showed no difference. Nicotine dependence score more than 4 points can be used as predictor of relapse. CONCLUSIONS: The smoking rate and the abstinence rate of smoker with ACS is higher than the general population, simple quit-smoking intervention do not increase the success rate of quit-smoking, indicated the need to strengthen the intervention in patients with ACS and smoking. PMID- 20356479 TI - [Diagnostic significance of B-type natriuretic peptide combined with noninvasive cardiac output monitoring in patients with dyspnea.]. AB - OBJECTIVE: To explore the clinical significance of carrying out fast blood B-type natriuretic peptide (BNP) detection together with noninvasive hemodynamic monitoring for pathogenic diagnosis in patients with dyspnea and to assess further the application value of noninvasive cardiac output monitoring in emergency room. METHODS: 354 patients were diagnosed as dyspnea in the Emergency Department of Chaoyang Hospital, being Affiliated to Capital Medical University during a period from May 2007 to January 2008 by using USCOM noninvasive ultrasonic cardiac output monitor to measure cardiac output (CO). If CO was less than 4 L/min, cardiac dyspnea will be diagnosed. Meanwhile, certain amount of venous blood was kept for rapid measuring of BNP concentration. If BNP concentration was higher than 100 pg/ml, cardiac dyspnea would be diagnosed. After diagnosis was made clearly, all the 354 patients were divided in two groups according to Framingham standards whether they had cardiac dyspnea or not and then comparison was carried out between the patients with the diagnosis of cardiac dyspnea with CO and BNP. The relationship between CO and BNP was studied as well. RESULTS: In a group of 127 patients with cardiac dyspnea, there was no difference in terms of the number of patients showing positive results with CO or BNP as judging criteria (122 vs 119, P = 0.393) and CO and BNP had negative correlation; while the results were opposite in a group of 227 patients with non cardiac dyspnea (102 vs 11, showing negative CO or BNP P = 0.000) and there was no correlation between BNP and CO. CONCLUSIONS: For patients with dyspnea in the emergency room, the value of BNP concentration of blood plasma to determine cardiac dyspnea is somewhat limited. Appling non-invasive ultrasonic cardiac output monitor in the emergency room to detect CO for identifying the cause of dyspnea is clinically valuable. PMID- 20356480 TI - [The clinical characteristics of etiologies, diagnoses and treatment of emergency gastrointestinal hemorrhage.]. AB - OBJECTIVE: To investigate the causes, clinical features, treatment and prognosis of gastrointestinal bleeding (GIB) patients in emergency department. METHODS: To analyze prospectively the clinical data of 168 GIB patients admitted to the emergency department of Peking Union Medical College Hospital during 2006.1 - 2006.12. RESULTS: (1) General data: male:female = 1.75:1 (107:61), mean age 13 - 87 (56.5 +/- 17.8) years with a peak in 60 - 69 years. The percentage of old patients was significantly higher than that of young and middle age (52.4% vs 19.6% and 28.0%, P = 0.000). (2) The incidence of acute gastric mucosal lesion in patients taking non-steroidal antiinflammatory drugs (NSAIDs) (18.5%) was significantly higher than that in patients not taking (0.7%, P = 0.000). (3) 86.9% (146/168) of the patients had anemia. (4) More patients who took emergency gastroscopy could be diagnosed than those patients who did not (89.4% vs 58.5%, P = 0.000), while no significant difference could be seen between patients who took emergency enteroscopy and patients who had non-emergency gastroscopy (20.0% vs 57.9%, P = 0.315). (5) The hemostatic ratio in GIB patients due to peptic ulcer was obviously higher than that in GIB patients due to other causes (86.0% vs 40.7%, P = 0.000). The rate of emergency operation for GIB patients was 1.8%. CONCLUSIONS: Most of the GIB patients admitted to tertiary general hospitals are elderly males. NSAIDs administration is one of the most important causes of upper GIB. Upper GIB patients should have gastroscopy as soon as possible, while emergency coloscopy is of little significance in cases with lower gastrointestinal hemorrhage. PMID- 20356481 TI - [A study of the central nervous system complications after hematopoietic stem cell transplantation.]. AB - OBJECTIVE: To study the incidence, risk factors and prognosis of central nervous system (CNS) complications after hematopoietic stem cell transplantation (HSCT) in order to prevent or reduce its occurrence, provide better diagnosis and treatment and improve the survival of the patients. METHODS: A total of 640 patients who consecutively underwent HSCT in our hospital between May 2001 and December 2007 were included. The clinical outcomes of the patients who developed CNS complications were analyzed. RESULTS: The patients received stem cells from haploidentical family members (Haplo, n = 289), identical siblings (IS, n = 237), unrelated donors (URD, n = 83), unrelated cord blood (n = 14), syngeneic siblings (n = 9) or autologous peripheral blood (n = 8). Fifty-seven of 640 patients (8.9%) developed CNS complications. The incidences were 12.0%, 13.5% and 3.4% in URD-HSCT, Haplo-HSCT and IS-HSCT respectively (P < 0.001). The incidences of CNS complications were 19.4% and 8.3% in cases who received or did not receive conditioning with TBI (P = 0.047). There was no significant difference in the incidences of CNS complications between children (15.3%) and adults (8.3%) (P = 0.072). Similar incidences of CNS complications were seen in patients with hematological malignancies (8.9%) and non-malignant hematological disorders (7.7%) (P = 1.000). Five of the 57 patients developed two kinds of CNS complications. The patterns of CNS complications included relapse (17 cases), infections (15 cases), cyclosporine or FK506 encephalopathy (9 cases), cerebral hemorrhage (8 cases), cerebral infarction (2 cases), Wernicke's encephalopathy (1 case), skull fracture (1 case), drug-related meningitis (1 case), hepatic encephalopathy (3 cases), post-transplant lymphoproliferative disorder (1 case) and undetermined causes (4 cases). The overall mortality in the patients who developed CNS complications was 57.9% and 66.7% of them died of CNS complications. CONCLUSIONS: CNS complications are not uncommon after HSCT and they have high mortality and poor prognosis. Our data suggest that haplo-HSCT, URD-HSCT and conditioning with TBI, but not the age and types of hematological diseases are the risk factors for development of CNS complications. Relapse and infections are the most common CNS complications in HSCT recipients. Early diagnosis and appropriate management are crucial to the improvement of clinical outcomes in these patients. PMID- 20356482 TI - [Evaluating type I interferon-inducible gene expression in patients with systemic lupus erythematosus.]. AB - OBJECTIVE: To explore the expression levels of interferon-inducible genes in patients with systemic lupus erythematosus (SLE), and to validate these gene expressions as potential biomarkers for the differentiation of disease flare and infection. METHODS: Peripheral blood was obtained from 48 SLE, 16 rheumatoid arthritis (RA) patients and 26 normal controls, and total RNA was extracted and reverse transcribed into complementary DNA. Real-time PCR technique was used to determine the gene expressions of MX1, OASL, OAS1, ISG15 and LY6E at transcription level. Univariate logistic regression analysis and multivariate conditional logistic regression model were applied to analyze 5 related factors for infection or activity. RESULTS: (1) The expression levels of MX1, OASL, OAS1, ISG15, and LY6E mRNA in SLE patients were significantly increased as compared with normal controls (P all < 0.01), while the expression levels of OASL, OAS1, ISG15 and LY6E mRNA in SLE patients were also higher than those in RA patients (P all < 0.05). (2) There were no significant difference between male and female patients of the 5 gene expression in SLE patients. (3) By logistic regression analysis, ISG15 and LY6E were independent risk factors for active SLE patients (P < 0.01), OASL expression was an independent risk factor for SLE patients with infection (P = 0.003). CONCLUSION: All the 5 interferon inducible genes are highly expressed in SLE patients, in which ISG15 and LY6E are independently associated with disease flare, while OASL may be helpful for the evaluation of infection in SLE patients. PMID- 20356483 TI - [The role of octahedral montone in colonic barrier protection in severe acute pancreatitis rat model.]. AB - OBJECTIVE: To investigate the protective mechanism of octahedral montone in rats with acute pancreatitis. METHODS: Seventy-two SD rats were randomly divided into a sham-operation (SO) group, a severe acute pancreatitis (SAP) group and a treatment with octahedral montone group. Retrograde pancreatic ductal injection of 5% cholate sodium in rats was used to establish SAP models. Sham operation was done with intraperitoneal injection of normal saline. In the treated group octahedral montone was given through enema half hour before inducing SAP model. Then, we evaluate the pancreatic injury and detect the level of TNF-alpha, diamine oxidase (DAO) and endotoxin. Western blot and RT-PCR were used to determine the expressions of the tight junction protein occludin in the endothelial cells of intestinal mucosa at the time of hour 3, 6, 12 after operation. RESULTS: (1) The pathological scores of pancreatitis were significantly higher in the SAP group than those in the treatment group and SO group (P < 0.05). (2) Compared with the SO group, the level of TNF-alpha in the SAP group and the treatment group was much higher (P < 0.05), but the level in the treatment group was lower than that in the SAP group (P < 0.05). (3) The serum concentration of DAO and endotoxin was significantly increased in the SAP group, and the concentration in treatment group was higher than that in the SO group (P < 0.01), but lower than that in the SAP group (P < 0.01). The occludin protein and mRNA expression in the SAP group was the lowest and the expression in the treatment group was higher than that in the SAP group (P < 0.01), but lower than that in the SO group (P < 0.01). CONCLUSIONS: Octahedral montone can improve the colonic barrier function, reduce the endotoxemia, and ameliorate the inflammation during acute pancreatitis. PMID- 20356484 TI - [The current situation and challenge of Helicobacter pylori infection treatment]. PMID- 20356485 TI - [A multicenter study of Chinese patent medicine wenweishu/yangweishu in the treatment of Helicobacter pylori positive patients with chronic gastritis and peptic ulcer]. AB - OBJECTIVE: To evaluate the efficacy of Chinese patent medicine wenweishu /yangweishu in the treatment of Helicobacter pylori (H. pylori) positive patients with chronic gastritis and peptic ulcer. METHODS: A randomized, controlled and multicenter trial was conducted in 642 H. pylori positive patients with chronic gastritis or peptic ulcer. They were randomized to three groups: PCM group (n = 222, pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, for 7 days); PCM plus wenweishu group (n = 196); and PCM plus yangweishu group (n = 224). (14)C breath test was performed 4 weeks after therapy. For the patients with gastric ulcer, ulcer healing was determined by endoscopy after therapy. RESULTS: Intention-to-treat H. pylori eradication rate for PCM group, PCM plus wenweishu group, and PCM plus yangweishu group were 57.2% (127/222), 62.2% (122/196), 60.3% (135/224), respectively (P = 0.295, 0.512). Per-protocol H. pylori eradication rates were 62.3% (127/204), 70.1% (122/174), 65.2% (135/207), respectively (P = 0.108, 0.532).Per-protocol analysis gastric ulcer healing rate were 61.9% (13/21) 100.0% (18/18), 86.4% (19/22) respectively. The healing rate in PCM plus wenweishu groups was statistically significantly higher than the rate in PCM group (P = 0.004). The rates of symptom relief in PCM plus wenweishu groups and PCM plus yangweishu were statistically significantly higher than the rate in PCM group (both P < 0.01). Side-effects were rare and comparable between groups. CONCLUSION: Although PCM combined with wenweishu or yangweishu in the treatment of H. pylori positive patients with chronic gastritis and peptic ulcer can not reach a significantly higher eradication rate, it can increase the rates of both gastric ulcer healing and symptom relief. PMID- 20356486 TI - [Levofloxacin-based triple therapy for first-line Helicobacter pylori eradication treatment: a multi-central, randomized, controlled clinical study]. AB - OBJECTIVE: To compare efficacy and tolerability of 7-day standard triple therapy versus 7-day levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori (H. pylori) infection. METHODS: Three hundred consecutive H.pylori positive patients were randomized to receive: clarithromycin, amoxicillin, lansoprazole (Group A: n = 150); or amoxicillin, levofloxacin, lansoprazole (Group B: n = 150). H. pylori status was rechecked by (13)C-urea breath test 4 weeks after the end of therapy. RESULTS: The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 74.5% (111/149) and 78.2% (111/142); and Group B, 82.4% (122/148) and 83.0%(122/147). Although the eradication rate achieved with levofloxacin-based triple therapy was higher than that with standard therapies in either ITT or PP analysis, but no significantly difference was found between the two triple therapies. The incidence of side effects was similar among groups. CONCLUSIONS: A 7-day levofloxacin-based triple therapy can achieve higher H.pylori eradication rate than standard regimen. The levofloxacin-based regimen can be one effective therapy for the first-line anti-H.pylori treatment. PMID- 20356487 TI - [Efficacy of second-line treatment based on moxifloxacin triple therapy for Helicobacter pylori infection]. AB - OBJECTIVE: To evaluate the efficacy and tolerability of moxifloxacin-based triple therapy as an alternative second-line treatment for Helicobacter pylori (H. pylori) infection. METHODS: A total of 109 patients, in whom the initial standard PPI triple therapy had failed to eradicate Hp infection, were included. Patients were randomized to one of the following 7-day treatment regimens: (1) rabeprazole 10 mg twice a day, moxifloxacin 400 mg/day and amoxicillin 1000 mg twice a day; and (2) rabeprazole 10 mg twice a day, bismuth salts 150 mg three times a day; clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day. The eradication rates and side-effect rates of these two regimens were compared. RESULTS: The eradication rates were 75.5% (40/53) and 83.3% (40/48) with moxifloxacin-based triple therapy, and 62.5% (35/56) and 71.4% (35/49) with bismuth-based quadruple therapy by intention-to-treat and per-protocol analyses (both P > 0.05) respectively. CONCLUSIONS: The 7-day moxifloxacin-based triple therapy has a high eradication rate with fewer side-effects. This regimen can be a safe and effective option as second-line treatment for H. pylori infection. PMID- 20356488 TI - [Efficacy of moxifloxacin-based triple therapy to eradicate Helicobacter pylori infection]. AB - OBJECTIVE: To evaluated the efficacy of 9-day moxifloxacin-based triple therapy as first- or second-line treatment to eradicate Helicobacter pylori (H. pylori). METHODS: Three hundred and thirteen H. pylori-positive patients without previous treatment (Group A), 51 Hp-positive patients with once-failed treatment (Group B) and 32 with twice-failed treatment (Group C) were recruited to receive moxifloxacin, esomeprazole and tinidazole (MET) for 9 days.H. pylori status was re-assessed 4 weeks after the end of therapy by urea breath test. The eradication rate and its 95% confidence interval (95%CI) were calculated in intention-to treat (ITT) and per-protocol (PP) analyses respectively. RESULTS: In ITT analysis, the Hp-eradication rate was 89.8% (95%CI: 86.7% - 93.0%) in Group A, 81.2% (75.3% - 90.9%) in Group B and 81.2% (66.1% - 92.6%) in Group C, among which no significant difference was observed (chi(2) = 4.339, P > 0.05). However, in PP analysis there was a significant difference among them [93.9% (90.9% - 96.4%) in Group A, 84.8% (79.1% - 93.6%) in Group B and 81.2% (66.1% - 92.6%) in Group C (chi(2) = 9.294, P < 0.01)]. The rates were significantly lower respectively in Group B (chi(2) = 4.885, P < 0.05) and in Group C (chi(2) = 7.023, P < 0.01) than that observed in Group A according to PP analysis. But there was no significant difference between the patients with first-treated active ulceration and with first-treated gastritis (chi(2) = 1.670, P > 0.05 in ITT, or chi(2) = 0.030, P > 0.05 in PP analysis). Eradication rate in patients with 3rd-treated gastritis was lower than that in patients with first-treated gastritis according to PP analysis (chi(2) = 8.076, P < 0.01). The compliance rate was 95.99% in all patients. CONCLUSION: Nine-day moxifloxacin-based triple therapy provides an optimal eradication rate with a good compliance as first-line or second-line eradication of Hp. PMID- 20356489 TI - [Role of 125I seed implantation in treatment of unresectable pancreatic cancer]. AB - OBJECTIVE: To study the role of (125)I seed implantation in the treatment of unresectable pancreatic cancer. METHODS: From April 2004 to march 2006, 66 untreated patients with locally advanced pancreatic cancer (LAPC) were randomized into two groups: Group A: (125)I seeds implantation (n = 31) and Group B: control (n = 34). The objective tumor response, clinical benefit response, toxicity, complications and survival of two groups were observed. RESULTS: In Group A, the overall response rate (PR + NC) was 80.6%. Clinical benefit response rate was 54.8%. No toxicity was observed. Gastrointestinal hemorrhage and pancreatic fistula occurred in 1 patient respectively in Group A. The survival rates of 6 and 12 months were 56.0% vs 31.4% and 16.8% vs 2.9% respectively in two groups (P < 0.05). The median survival time of two groups was 8.0 months vs 4.0 months (P < 0.05). CONCLUSION: (125)I seed implantation is a simple, safe and effective method in the treatment of locally advanced pancreatic cancer. PMID- 20356490 TI - [Effect of tumor vascular invasion upon cardio-pulmonary exercise functions in patients with lung cancer]. AB - OBJECTIVE: To investigate the correlation between the tumor vascular invasion and the change of cardio-pulmonary exercise function in patients with lung cancer. METHODS: The cardio-pulmonary exercise test was performed in 405 patients with lung cancer (293 with vascular invasion and 112 without). The peak load indices examined included maximal work power (measured value/predicted value, W%), maximal oxygen uptake per weight (VO(2)/kg), anaerobic threshold (AT), maximal oxygen pulse (measured value/predicted value, VO(2)/HR%), maximal minute ventilation (V(E)), maximal breath reserve (BR), maximal breath frequency (BF) and maximal tidal volume during expiration (VTex). RESULTS: (1) W%, VO(2)/kg, AT, VO(2)/HR% of patients with vascular invasion [(73 +/- 18)%, (17 +/- 5) ml * min( 1) * kg(-1), (51 +/- 14)%, (79 +/- 18)% respectively] decreased than those without vascular invasion [(86 +/- 20)%, (19 +/- 5) ml * min(-1) * kg(-1), (55 +/ 14)%, (88 +/- 20)% respectively, all P < 0.01) while BF increased [(32.1 +/- 6.1)/min vs (30.6 +/- 5.1)/min, P < 0.05). (2) The patients were divided according to TNM stage, number, kind of tumor vascular invasion and its relationship with tumor, W%, VO(2)/HR% decreased in the groups of 1-, 2- and >or= 3-vessel invasion versus the control group (P < 0.01), AT decreased in the groups of 1- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the groups of 2- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the group of >or= 3 vessel invasion versus 1- and 2-vessel invasion (P < 0.05 or P < 0.01), VO(2)/HR% decreased in the group of >or= 3-vessel invasion versus 1-vessel invasion (P < 0.01), VTex decreased in the group of >or= 3-vessel invasion versus the control group and 1-vessel invasion (P < 0.05). There was correlation between VO(2)/HR% and the number of tumor invaded vessels (r = 0.220, P < 0.01). CONCLUSIONS: The amount of oxygen uptake, exercise ability and cardiac function during exercise decrease in patients of lung cancer with tumor vascular invasion. The main reason is the number of the invaded vessels. PMID- 20356491 TI - [Efficacy study of single-agent gemcitabine versus gemcitabine plus carboplatin in untreated elderly patients with stage IIIb/IV non-small-cell lung cancer]. AB - OBJECTIVE: To explore a chemotherapeutic regimen suitable for non-small cell lung cancer (NSCLC) in elderly patients. METHODS: A total of 68 elderly patients with NSCLC (stage IIIb/IV) were equally and randomly divided into single-agent and combined groups. Patients in single-agent group received gemcitabine 1000 mg/m(2) at Days 1 and 8 for a 21-day cycle. Those in combined group received gemcitabine 1000 mg/m(2) at Days 1 and 8 in combination carboplatin AUC5 at Day 2 for a 21 day cycle. The drugs were intravenously administered. All patients received 3 cycles of treatment. RESULTS: In single-agent and combined groups, CR 1 and 1, PR 12 and 13, response rates 38% and 41% were respectively observed. There was no statistically significant difference between two groups (P > 0.05). The 1-year and 2-year survival rates of single-agent and combined groups were 31% vs 32% and 12% vs 14% with a median survival of 9.9 and 9.8 months without a statistically significant difference (P > 0.05). The rates of leucopenia and thrombocytopenia (III-IV degree) were 47% and 38% in combined group and they were higher than 24% and 15% in single-agent group with a statistically significant difference (P < 0.05). The observer scale of lung cancer symptom scale showed that the post treatment scores of appetite, fatigue and pain significantly improved in single agent group while no improvement was observed in combined group. Also the scores of appetite, fatigue and pain of single-agent group were higher than those of combined group after chemotherapy (P < 0.05). CONCLUSION: Single-agent gemcitabine regimen is more suitable for advanced NSCLC in elderly patients. PMID- 20356492 TI - [An economic evaluation of low dose recombinant human tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism]. AB - OBJECTIVE: To compare and evaluate the cost and effectiveness between recombinant human tissue-type plasminogen activator (rt-PA) 50 mg and 100 mg regimen for the treatment acute pulmonary thromboembolism (PTE). METHODS: Based on a randomized clinical trial data, 118 cases were enrolled, 65 cases in group 50 mg and 53 cases in group 100 mg, which showed the similar efficacy and safety of rt-PA 50 mg and 100 mg. Progressive improvement in pulmonary artery obstructions was found to be similarly significant in both treatment groups, but there was no significant differences between the two groups (89.1% vs 89.6%, chi(2) = 0.007, P = 0.936). The rates of adverse events in two groups were same as well (17% vs 32%, chi(2) = 3.704, P = 0.054). We compared the cost directly and the cost effective rate of the two groups. Based the cost saving of individual patient, prevalence rate of acute PTE, and co-pay rate of reimbursement, we calculated the cost saving of societal and payer's perspective. RESULTS: The cost of group 50 mg is 6352 RMB/person, and the cost of group 100 mg is 12,704 RMB/person. The cost effect rates of the two groups were 7129 and 14,179 separately. With the same effect, each patient in 50 mg group can save 7050 RMB. If the PTE patients in China were treated with rt-PA 50 mg instead of 100 mg, the society cost saving would be 443,604,624 RMB. CONCLUSION: rt-PA 50 mg/2 h regimen, compared with 100 mg/2 h, can not only provide similar efficacy and safety, but also show a good health economic saving. PMID- 20356493 TI - [Percutaneous coronary intervention of patients with complex small coronary artery lesion unsuitable for coronary artery bypass graft]. AB - OBJECTIVE: To investigate the safety and efficacy of percutaneous coronary intervention (PCI) in patients with low left ventricular ejection fraction (LVEF) and complex small coronary artery lesions. METHODS: Complete or partial post-PCI revascularization of coronary artery was employed in 16 patients with a low LVEF and complex small coronary artery lesions who were unsuitable for CABG (coronary artery bypass grafting). All cases were observed with regards to immediate success rate of operation, complication, hospitalization duration, improvement of cardiac function and LVEF and major adverse cardiac events (including cardiac death, myocardial infarction and target lesion revascularization) at 12 months post-operation. RESULTS: All cases were successfully treated without death and severe complications while the hospitalization duration was (11 +/- 5) days. The follow-up survey at 12 months post-operation showed that no major adverse cardiac event occurred, the post-operative improvement of cardiac function was from III - IV grade to I - II grade, the improvement of LVEF was from 25% - 45% [(29 +/- 8)%] to 32% - 48% [(37 +/- 7)%], left ventricular end diastolic diameter (LVDd) was shortened from 52 - 79 (66 +/- 11) mm to 49 - 68 (58 +/- 8) mm. The reexamination of 14 cases by coronary angiography at 12 months post-operation showed that there was no intra-stent thrombosis while 20% - 40% intra-stent restenosis occurred in 2 cases. CONCLUSION: For patients with a low LVEF and complex small coronary artery lesions, PCI is a safe and effective method to lower the mortality rate of CHD patients with heart failure and improve the long term patient prognosis. PMID- 20356494 TI - [Early diagnosis and treatment of invasive pulmonary aspergillosis following kidney transplantation]. AB - OBJECTIVE: To investigate the early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) infection following kidney transplantation. METHODS: A retrospective analysis was carried out in 16 IPA patients after kidney transplantation from January 2002 to March 2008. There were 7 males and 9 females with a mean age of 42.9 years old. The prevalence of IPA was 2.21%. The induction therapy was given to 12 patients, 5 with CD25 monoclonal antibody and 7 with anti thymocyte globulin (ATG). All 6 with acute pre-infection rejection were given the methylprednisolone sodium or ATG therapy. RESULTS: The intervals between transplantation and diagnosis were largely within 3 months. Persistent or intermittent fever was the main post-operative symptom. High resolution computed tomography (HRCT) of thorax and bronchoalveolar lavage fluid (BALF) for culture were the main evidence of clinical diagnosis. Amphotericin B (0.15 - 0.5 mg * kg( 1) * d(-1)) might be the major treatment for IPA because of its satisfactory initial therapeutic effect. The mortality rate was 7/16 (43.75%). Of the 9 surviving patients, 8 were treated before the test results were available. CONCLUSIONS: The clinical symptoms of IPA following kidney transplantation are atypical in the early stage so that it is easy to misdiagnoses and a high mortality rate ensues. Major risk factors for IPA include administration of ATG, CD25 monoclonal antibody and steroid boluses for prevention or treatment of allograft rejection; prolonged broad-spectrum antibiotic use after transplantation and environmental factors. Early diagnosis and empirical use of antifungal agents while waiting for a definitive diagnosis are imperative in achieving a favorable outcome. PMID- 20356495 TI - [Clinical study of eosinophilic gastroenteritis]. AB - OBJECTIVE: To study the clinical symptoms, diagnosis and treatment of eosinophilic gastroenteritis (EG). METHODS: A total of 44 cases of EG admitted to our hospital were studied respectively in clinical manifestations, laboratory examinations, endoscopic signs and treatment. RESULTS: (1) The presenting symptoms of EG patients was abdominal pain. (2) The endoscopic signs of EG were mucosal pathological changes of hyperemia, erosion and hyperplasia. A certain number of eosinophilic granulocytes were detected in pathological examination. (3) The hormones were effective and had quick onsets. While, based on different clinical symptoms, the traditional medicine was dosed by oral administration and intestinal enema. In TCM group (n = 22), 20 patients had a relief of clinical symptoms, 4 cases of recurrence and 16 of cure. In comparison, in hormone group (n = 18), 17 patients had a relief of clinical symptoms, 6 cases of recurrence and 12 of cure. The results showed that two groups had no statistical difference in relief of clinical symptoms, recurrence and hormonal cure (all P > 0.05). But it will be more readily accepted. CONCLUSIONS: The incidence of EG is low in clinical practice because of its non-specific clinical and endoscopic manifestations. An elevated count of eosinophilic granulocytes in peripheral blood, ascitic fluid and tissues of mucous membrane are key diagnostic points. The hormonal treatment is both fast and effective. But traditional medicine will have a brighter clinical prospect. PMID- 20356496 TI - [Screening of high-risk group with colorectal cancer]. AB - OBJECTIVE: To measure the rate of high-risk group and the detection rate of colorectal cancer (CRC) in communities in Guangdong province and to provide scientific rationales for formulating mass screening plans in high-risk group. METHODS: Mass survey was conducted by questionnaire combined fecal occult blood test (FOBT) in Huizhou region, Guangdong Province, to sort out the high-risk population of CRC. Then the high-risk population was screened by colonoscopy and pathology to identify CRC. The differences were compared by direct expenditure which was used to calculate screening cost. RESULTS: A total of 68,953 people were surveyed. There were 940 people in high-risk group (detection rate: 1.36%), 3118 in immunity FOBT positive group (detection rate: 4.52%), Merging aforementioned two groups, there were 3870 in population at risk (detection rate: 5.61%). The CRC detection rate in high-risk group, immunity FOBT positive group, population at risk and average-risk group was 506.3/10(5), 314.3/10(5), 315.9/10(5) and 17.7/10(5) respectively. The positive predictive value of CRC screening scheme by high-risk group questionnaire-colonoscopy was 0.43% while CRC screening scheme by FOBT-colonoscopy 0.22%. In terms of direct expenditure of CRC per case in high-risk group and immunity FOBT positive group was 47,834.5 yuan and 82,303.6 yuan. The latter was 1.7 times than that of the former. CONCLUSIONS: The scheme of questionnaire combined FOBT for CRC is an effective way in mass survey. The scheme by high-risk group questionnaire-colonoscopy has a much better cost-effectiveness than that of the scheme by FOBT-colonoscopy so that it should be one of the preferred methods for individual screening in high-risk group. PMID- 20356497 TI - [Islet perifusion: a new method to evaluate first-phase insulin secretory function of beta-cell in vitro]. AB - OBJECTIVE: To set up islet perifusion system, a new method to evaluate first phase insulin secretory function of beta-cell in vitro. METHODS: Islet perifusion system was set up, including perifusion framework, waterbath system, infusion pump system, afferent system, islet capsule, and efferent system. Kinetics of insulin release in vitro was studied using the perifusion system. Pancreatic islets were isolated as mentioned above and used freshly after isolation. Size matched 50 islets were placed in each column. Then the columns were gently closed with the top adaptors, immersed in vertical position and controlled temperature in the water bath at 37 degrees C. The perifusion medium was maintained at 37 degrees C in a water bath. And all columns were perifused in parallel at a flow rate of 0.5 ml/min with KRBB (2.8 mmol/L glucose) at 37 degrees C. After 60 min static incubation with KRBB (2.8 mmol/L glucose), the islets were stimulated in the continuous presence of a high concentration of 16.7 mmol/L glucose. Samples were collected every 20-second until 2 min, every 1 min until 5 min, thereafter every 5 min until 30 min. Samples were immediately stocked at -80 degrees C until further analysis. Insulin concentration was measured with an insulin RIA kit. RESULTS: An Islet perifusion system was established successfully, and kinetic curves of insulin secretion of db/m and db/db mice were traced out. CONCLUSION: An established islet perifusion system, could be widely used to evaluate insulin secretory function of beta-cell in in vitro research of diabetes. PMID- 20356499 TI - [Neuroprotective treatment in ischemic stroke: when the dream comes true.]. PMID- 20356498 TI - [Effect of anti-cancer drugs on the expression of BIC/miR-155 in human pancreatic cancer PANC-1 cells]. AB - OBJECTIVE: To investigate the effect of anti-cancer drugs on the expression of B cell integration cluster (BIC) RNA/miRNA-155 in human pancreatic cancer PANC-1 cells. METHODS: PANC-1 cells were treated with different concentrations of anti cancer drugs. Total RNA of the treated cells were harvested and the expression levels of BIC RNA and mature miR-155 were quantified by using Taqman FAM/MGB probes on a real-time PCR system. Relative quantification was carried out using the DeltaDeltaCt method. A PI3K-related kinases inhibitor was used to determine whether these kinases were involved in the regulation of BIC RNA. RESULTS: The expression of BIC RNA was strongly induced by anti-cancer drugs. When PANC-1 cells were treated by gemcitabine with concentrations of 1.0, 2.5, 5.0, 10.0 mg/L for 48 h and 72 h, the level of BIC RNA (48 h: 37.1 +/- 4.1, 29.0 +/- 5.7, 21.0 +/- 7.6, 40.4 +/- 9.0, 72 h: 27.7 +/- 3.1, 43.1 +/- 1.2, 31.8 +/- 5.4, 23.1 +/- 1.4) were significantly higher than that of the control (48 h: 1.6 +/- 1.1, 72 h: 1.0 +/- 0.1, all P < 0.05). 5-FU (10 mg/L, 48 h) and bleomycin (100 mg/L, 48 h) also induced BIC RNA up-regulation (5.2 +/- 1.1 vs 1.7 +/- 0.7, 11.5 +/- 0.7 vs 1.7 +/- 0.7, both P < 0.05). When PANC-1 cells treated with 1.0, 2.5, 5.0, 10.0 mg/L gemcitabine for 72 h, the level of miR-155 (2.21 +/- 0.40, 1.86 +/- 0.03, 2.47 +/- 0.04, 3.24 +/- 0.05) also higher than that of the control (1.11 +/- 0.09, P < 0.05), while no change was observed when the cells only treated for 48 h. Further study showed gemcitabine-induced BIC RNA up-regulation was inhibited by wortmannin, a specific PI3K inhibitor, the expression levels of BIC RNA of 1 micromol/L wortmannin + 5 mg/L gemcitabine group and 10 micromol/L wortmannin + 5 mg/L gemcitabine group were 5.34 +/- 1.11 and 1.26 +/- 0.07, lower than that of 5 mg/L gemcitabine group (11.82 +/- 3.11, P < 0.05). CONCLUSIONS: BIC RNA is strongly induced by anti-cancer drugs in PANC-1 cells and the levels of miR-155 also slightly increase. PI3K pathway is involved in gemcitabine-induced BIC RNA up-regulation. PMID- 20356500 TI - [Neuroimaging and cognitive disorders.]. PMID- 20356501 TI - [China predominantly needs improved prevention of cardiovascular diseases.]. PMID- 20356502 TI - [Combined anti-hypertensive and anti-atherosclerosis treatment for patients with high blood pressure.]. PMID- 20356503 TI - [The prevalence of combined extra- and intra-cranial artery stenosis in patients with extracranial internal carotid artery occlusive disease.]. AB - OBJECTIVE: The intra-cranial arteries are more affected in Asian ischemic stroke patients. We thought that tandem or diffuse arterial occlusive disease may be more common among patients with extracranial internal carotid artery (ICAex) occlusive disease. In the current study, the frequency of other co-existing extracranial artery (EA) or intracranial artery (IA) stenosis in patients with ICAex occlusive disease and its risk factors were studied. METHOD: One hundred and ninety-eight consecutive patients with ischemic stroke or TIA who were admitted to our hospital from Jan 2001 to May 2008 and who had stenosis (70%) or occlusion of ICAex were enrolled in the study. All the patients were examined with carotid duplex and transcranial Doppler (TCD). Among them, 75 patients were also examined with DSA, 52 patients with intracranial MRA and 25 patients with extra- and intra-cranial CTA. Extracranial artery stenosis or occlusion were diagnosed with DSA/CTA in 93 patients, and with carotid duplex only in 105 patients. Intracranial artery stenosis was diagnosed with DSA/MRA/CTA in 118 patients, and with TCD only in 80 patients. Patients with presumably cardioembolism such as atrial fibrillation were excluded. RESULTS: Among the 198 patients, 172 (86.8%) had other combined EA or IA stenosis. One hundred and thirty-five patients (135/198, 68.2%) had other combined EA stenosis, which were more frequently found in the contralateral ICAex (71/198, 35.9%). One hundred and twenty-three patients (123/198, 62.1%) had combined IA stenosis, which were more frequently found in MCA (75/198, 37.9%). 52 (52/198, 26.3%) had ipsilateral terminal ICA and/or middle cerebral artery stenosis. CONCLUSION: Tandem or diffuse arterial occlusive disease is common among patients with steno-occlusion of ICAex. Therefore, it is important to evaluate other EA and IA stenosis before CEA or CAS in Chinese patients. PMID- 20356504 TI - [A diffusion tensor magnetic resonance imaging for studying white matter changes in patients with mild cognitive impairment.]. AB - OBJECTIVES: To measure the microstructural differences in the brains of participants with amnestic mild cognitive impairment (aMCI) and compare with a control group using a magnetic resonance diffusion tensor imaging (DTI) technique with fully automated image analysis tools. METHODS: A standardized clinical and neuropsychological evaluation was conducted on each subject. 31 participants (15 participants with aMCI, 16 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control the effects of anatomical variation, the diffusion images of all participants were registered to standard anatomical space. Voxel-by-voxel comparisons showed significant regional reductions in white matter regions of fractional anisotropy (FA) in the participants with aMCI as compared with the controls. RESULTS: Significantly decreased FA value measurements (P < 0.001) were observed in the right frontal white matter in participants with aMCI. Moreover, there was a statistically significant difference between the patients with aMCI and controls in considering the small regions of bilateral superior frontal gyrus white matter (P < 0.001). CONCLUSIONS: White matter damage of frontal lobe may play an important role in histopathologic changes associated with amnestic mild cognitive impairment. PMID- 20356505 TI - [A clinical comparative study of multiple sclerosis and neuromyelitis optica.]. AB - OBJECTIVE: To compare the clinical characteristics of multiple sclerosis (MS) and neuromyelitis optica (NMO) for better diagnosis and differential diagnosis of them. METHODS: The characteristics of 40 MS and 38 NMO cases were retrospectively studied on clinic manifestations, electroneurophysiology, some laboratory indices, imaging characteristics and so on. RESULTS: The ratios of male to female were 1:1.35 and 1:4.43 respectively in patients with MS and NMO, so patients with NMO were more likely to be female as compared with MS (P < 0.05). The mean onset age was (35.5 +/- 13.9) years in MS patients and (30.6 +/- 15.6) years in NMO patients, but no significant difference was found (P > 0.05). The cases of visual acuity V(5) > V(3)) and inverteted T wave (especially in V(3-5) leads and the voltage of the inverteted T waves may be up to >/= 10 mm). The major feature of echocardiography was the thickening of left ventricular apical wall to 15 - 37 (18.0 +/- 3.3) mm. The final follow up showed that the mean thickness of the apical wall was (19.7 +/- 3.7) mm. The ratio of the thickness of left ventricular apical wall to posterior wall before and after the follow up was 1.7 +/- 0.3 and 1.9 +/- 0.9 respectively, with significant statistical difference (P < 0.05). There was no difference in the left ventricular end-diastolic dimension and left ventricular ejection fraction. The main cardiovascular events were atrial fibrillation (16 cases), heart failure of NYHA III-IV class (3 cases), anterior wall myocardial infarction (1 case) and sudden death (1 case). CONCLUSIONS: The final diagnosis of ApHCM depends on the characteristic inverteted T wave in ECG and apical hypertrophy in echocardiography. The prognosis of ApHCM is rather good for its progression is relatively slow. PMID- 20356508 TI - [To compare negative expiratory pressure technique with conventional tests in detecting expiratory flow limitation in chronic obstructive pulmonary diseases patients.]. AB - OBJECTIVE: To compare negative expiratory pressure (NEP) technique with conventional test in detecting expiratory flow limitation (EFL) in chronic obstructive pulmonary diseases (COPD) patients. METHODS: EFL was measured with NEP technique and conventional method respectively in 72 COPD patients;EFL was measured with NEP technique in 20 COPD patients who failed to perform conventional test. RESULTS: EFL was detected in 54 of the 72 COPD patients. NEP test was successfully performed on the 20 patients, and 19 of them were found with EFL. The level of forced expired volume in one second percentage (FEV(1)%) of the patients with 2-score group (46.92 +/- 12.74)% and 3-score group (33.35 +/ 8.96)% were significantly lower than that of the 1-score group (63.60 +/- 16.65)%. Area under curve of NEP technique and conventional test in ROC is 0.903 and 0.761 respectively. CONCLUSIONS: As compared with conventional test, EFL detected with NEP technique is more reliable in evaluating dyspnea of COPD patients. It is simple and doesn't require any cooperation of the patients. NEP technique can be applied in COPD patients who fail to receive conventional test. PMID- 20356509 TI - [The diagnosis and treatment of duodenal lipoma.]. AB - OBJECTIVE: To summarize the clinical features of the duodenal lipomas in order to explore effective diagnostic methods and appropriate treatment preoperatively. METHODS: The clinical features, laboratory results, endoscopic appearance, radiological and pathological data of 8 cases of duodenal lipoma were retrospectively analyzed. RESULTS: Four patients suffered with repeated melena, 3 cases with epigastric discomfort, sour regurgitation or hiccup, while 1 patient without any symptoms. Liver functions, serum lipids and tumor markers were normal in all patients. Six patients had been detected lesions by gastroscopy (2 cases missed diagnosed in the first examination), these lesions were appeared in duodenal bulb (2 cases) or descendant duodenum (4 cases). Abdominal CT examination revealed partial duodenal wall thickening (6 cases), partial enteric cavity narrowing (4 cases), or low-density lesions in enteric cavity (3 cases) with CT value of -85 HU and evenly intensified when enhanced. EUS showed intensive hyperechoic lesions from submucosa, with homogeneous echo and clear margin. Biopsy under endoscopy in all patients showed chronic inflammation of mucosa, while the pathologic diagnosis was lipoma after surgical excision or endoscopic resection. Pancreaticoduodenectomy performed in 1 patient, duodenal tumorectomy in 3 patients and endoscopic resection with snare in 4 patients. CONCLUSION: Common site of duodenal lipoma is descending part, and the clinical manifestations are non-specific. Imaging and endoscopic examination are the mainly methods to detect the lesion, while EUS is significantly valuable in diagnosing and differential diagnosing. It can be treated by partial tumorectomy or endoscopic trap resection. PMID- 20356510 TI - [The characteristics of peripheral lymphocytic subsets and cytokines in primary biliary and their changes to drug treatment.]. AB - OBJECTIVE: To investigate the characteristics of peripheral lymphocytic subsets and cytokines in patients with primary biliary cirrhosis (PBC) and their changes after therapy. METHODS: Eighty two patients with untreated PBC were divided randomly into three groups. Group U (28 patients) were treated with ursodeoxycholic acid (UDCA), group UP (27 patients) were treated with UDCA and prednisonlone, while group UA (27 patients) were treated with UDCA and azatharaprine. Levels of peripheral lymphocytic subsets and cytokines were monitored at 0, 3, 6 months after therapy. Twenty healthy people were included as healthy control (HC). RESULTS: Compared with HC, the percentage of CD(4)(+)T cell (P = 0.044) increased in PBC; the levels of IFNgamma (P = 0.001), IL-2 (P = 0.000), IL-4 (P = 0.010), IL-6 (P = 0.029), tumor necrosis factoralpha (TNFalpha) (P = 0.000), IL-1beta (P = 0.008) and transforming growth factorbeta (TGFbeta) (P = 0.069) increased in PBC. The level of TNFalpha in peripheral was correlated with those of ALT (P = 0.005), AST (P = 0.002), total bilirubin (TBil) (P = 0.001), direct bilirubin (DBil) (P = 0.002), and mayo risk score (MRS) (P = 0.020). The percentage of CD(4)(+)T cell decreased in group U. In group U, the levels of IFNgamma, IL-4, IL-6 all decreased after therapy at the third month, but rebounded thereafter. In group of UP and UA, the levels of IFNgamma, IL-4, IL 6 were suppressed below the levels of baseline after therapy. Levels of TNFalpha and IL-2 decreased in all three groups after therapy. CONCLUSIONS: Levels of both Th1 and Th2 related cytokines are abnormal in the peripheral blood of patients with PBC. The abnormal levels of Th1 related cytokine indicated that PBC is a cell immunity based autoimmune disease. IFNgamma, TNFalpha are directly related to the disease. The three treatments have different effects on the adjustment of the immune system. PMID- 20356511 TI - [A pilot study of protein fingerprinting in brain-gut interaction model of irritable bowel syndrome.]. AB - OBJECTIVE: Matrix-assisted laser desorption ionization-time of might-mass spectrometry (MALDI-TOF-MS) was utilized to analyze the protein fingerprint in brain-gut interaction of irritable bowel syndrome (IBS) model rats' colon, so as to find the clues for IBS. METHODS: Fourteen healthy male adult Wistar rats were selected and divided into a control and a chronic and acute stress (CAS) group. Colon motility, visceral sensation and behavior changes of rats were detected to evaluate the model. MALDI-TOF-MS was used to observe the overall view of protein in colon so as to study whether there are abnormalities of protein levels in IBS. RESULTS: As compared with those in the control group, the number of fecal pellets [(6.00 +/- 1.69) pellets/1 h vs (1.14 +/- 0.69) pellets/1 h, P < 0.01] and frequency of abdominal contraction induced by colorectal distention (CRD) increased, while the amount of weight gain [(298.88 +/- 18.61) g vs (348.00 +/- 12.44) g, P < 0.01] and consumption of sucrose solutions [(13.63 +/- 1.69) ml/1 h vs (19.00 +/- 3.06) ml/1 h, P < 0.05] decreased in the CAS group (P < 0.05). As far as protein/peptide quality different peak was concerned, CAS rats had 12 different peaks compared with the control rats. The different proteins could be divided into 4 types, which were related to iron secretion, protein synthesis, G protein system and immunity. The protein levels of the model group were higher than those in the control group (P < 0.05). CONCLUSIONS: The CAS rats integrate the major characteristics of IBS such as altered colon motility, higher visceral hypersensitivity and psychiatric disorder and can mimic the brain-gut interaction of IBS partly. The detection of differential proteins provides reference for the pathogenesis and treatment of IBS. PMID- 20356512 TI - [The polymorphism of cytochrome P(450) 2C19 gene in patients with invasive fungal infections.]. AB - OBJECTIVE: To investigate the polymorphism profile of cytochrome P(450) 2C19 (CYP2C19) in Chinese patients with invasive fungal infections. METHODS: Two major single nucleotide polymorphism loci of the CYP2C19 gene (CYP2C19*2 and CYP2C19*3) were genotyped with PCR and restriction fragment length polymorphism (PCR-RFLP) in 134 patients with invasive fungal infections and 134 healthy volunteers. Allele frequencies and the proportions of metabolizer phenotypes were compared. RESULTS: In patients with invasive fungal infections, CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles showed frequencies of 58.2%, 36.6% and 5.2%. In healthy volunteers, the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 63.4%, 34.3% and 2.2%. There was no significant difference in allele frequencies between the two groups. Of the patients with invasive fungal infections, 33.6% were homozygous extensive metabolizers, 50.0% heterozygous extensive metabolizers and 16.4% poor metabolizers. Of the healthy volunteers, 40.3% were homozygous extensive metabolizers, 48.5% heterozygous extensive metabolizers and 11.2% poor metabolizers. The proportions of metabolizer phenotypes were similar between the two groups. CONCLUSIONS: Significant CYP2C19 polymorphism was detected in both groups. Approximately two thirds of the Chinese patients were either heterozygous extensive metabolizers or poor metabolizers. The genetic polymorphism may have important effect on drug metabolism in these patients. PMID- 20356513 TI - [The establishment and evaluation of diagnostic accuracy of AllGlo(TM) probe based techniques for invasive aspergillosis.]. AB - OBJECTIVE: To establish and evaluate a diagnostic technique based on the AllGlo(TM) probe for the invasive aspergillosis. METHODS: With the self-designed AllGlo(TM) probes and primers and the standards, two standard curves of the real time PCR based on AllGlo(TM) probes were established respectively for A. flavus and A. fumigatus, then its specificity, sensitivity and reproducibility were evaluated respectively. RESULTS: The findings indicated that the standard curve of A. flavus was Y = -3.003X + 36.825, and A.fumigatus' was Y = -3.052X + 38.016, and their interassay coefficient of variation respectively were 15.60% and 12.94%, suggesting a good reproducibility. The lowest spore concentration they could be detected was 10 CFU/ml, which equated to 100 - 1000 copies of internal transcribed spacer (ITS)2 genes, suggesting a good sensibility. They didn't have cross-positive reaction with other fungus, human genome and bacteria, which indicated a good specificity. CONCLUSION: The diagnostic technique based on the AllGlo(TM) probe for the invasive aspergillosis possessed a good sensitivity, good specificity and deadly accuracy. PMID- 20356515 TI - [60 years review of national medical journal of China, the brilliant past, the heavy duty future]. PMID- 20356514 TI - [Expression of bone marrow macrophages antigen activation and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells Coombs test.]. AB - OBJECTIVE: To explore the expression of antigen activated of macrophages (MPhi) of bone marrow and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells (BMMNC)-Coombs test (immunorelated pancytopenia, IRP). METHODS: Sixty-one IRP patients, 10 severe aplastic anemia (SAA) patients and 13 healthy controls were enrolled in this study. The categories of auto-antibodies (IgG, IgM) on BMMNC (CD(34)(+)/CD(15)(+)/GlycoA(+) hematocytes), the quantity (CD(68)(+)/CD(45)(+))% and expression of antigen activated (CD(69)) of MPhi (CD(68)(+)CD(69)(+)/CD(+)(68))% in bone marrow of all cases and controls were measured by fluorescence activated cell sorting (FACS). RESULTS: The quantity and expression ratio of activated antigen of bone marrow (BM) MPhi in IRP patients [(0.57 +/- 0.30)% and (40.30 +/- 18.49)%] were respectively significantly higher than those in SAA [(0.46 +/- 0.08)% and (32.44 +/- 19.37)%] and healthy controls [(0.44 +/- 0.69)% and (29.71 +/- 11.67)%] (both P < 0.05). The quantity presented high-positive correlation with the expression ratio of activated antigen of BM MPhi (r = 0.89, P < 0.01). Patients with IRP were classified into two subgroups according to the quantity of MPhi: Group A (MPhi >/= 0.5%, 34 cases) and Group B (MPhi < 0.5%, 27 cases). Thirty-two cases (94.12%) were with auto antibody (IgG) in Group A, while only 2 (7.41%) with auto antibody (IgG) in Group B. There was significant difference in expression ratio of activated antigen of BM MPhi between Group A (49.19 +/- 16.63)% and Group B (29.11 +/- 14.30)% (P < 0.05), but no difference was found between Group B and the control group (P > 0.05). Total curative rates at 3 and 6 month (47.06% and 79.41%) of Group A were better than those of Group B (22.22% and 51.85%). Thirty four IRP patients with autoantibody (IgG)(+) were divided into two subgroups according to the quantity of MPhi: high level group (>/= 0.75%, 9 cases) and low level group (< 0.75%, 25 cases), 24 cases (96%) in MPhi low level group were found auto-antibody (IgG) on one hemotopoietic cell lineage, 1 on two lineages, while 8 (88.89%) in MPhi high level group were detected auto-antibody (IgG) on two cell lineages, and 1 on three cell lineages. Expression ratio of activated antigen (56.12 +/- 15.11)% was much higher in MPhi high level group than that in MPhi low level group (44.58 +/- 18.16)% (P < 0.05). The count of red blood cell concentration of hemoglobin and platelet in peripheral blood in MPhi high level group were respectively lower than those in MPhi low level group, while the percentage of Ret, the level of total bilirubin and indirect bilirubin, the ratio of erythroid of sternal bone marrow in MPhi high level group were higher than those in MPhi low level group. CONCLUSION: The expression of activated antigen of BM MPhi was enhanced in IRP especially with auto-antibody (IgG), which might be involved in damage process of hemotopoietic cell. PMID- 20356516 TI - [Consensus on the drug treatment of peritumoral brain edema]. PMID- 20356517 TI - [Gait analysis after anterior cruciate ligament reconstruction with different methods]. AB - OBJECTIVE: To examine and compare the gait patterns of subjects with hamstring and patellar tendon graft reconstructions of anterior cruciate ligament (ACL). METHODS: Three groups were compared: 19 patellar tendon anterior cruciate ligament reconstruction patients (a mean of 11.8 weeks after injury), 19 hamstring tendon anterior cruciate ligament reconstruction patients (a mean of 10.4 weeks after injury) and 19 matched controls. Gait analysis was performed using the DorealSoft DVMC-8801 three-dimensional motion capture system. Kinematic data were recorded for the lower limb prior to and 3, 6, 9 and 12 months after ACL reconstructive surgery. Each subject was asked to walk on a motorized treadmill with different slopes and perform-after 6 minutes of familiarization time- at least 2 minutes of walking at a constant speed of 1.9 km/h. RESULTS: All the ACL-deficient patients exhibited a quadriceps avoidance pattern prior to and 3 months post-operation. In the operated individuals, the spatial-temporal parameters and the knee angle had already regained a normal pattern for the ACL deficient limb during gait at 6 months post-operation. However, the angular acceleration showed no significant statistical difference with the values of healthy control group at just 9 months post-operation. The flexion angular acceleration at 15 degrees treadmill was significantly smaller than that in the hamstring tendon group and the extension angular acceleration was significantly smaller than that in the patellar tendon group at 6 months post-operation. CONCLUSION: ACL surgical repair significantly alters the lower-extremity gait patterns and the establishment of pre-injury gait patterns takes at least 9 months to occur. The graft-specific differences in knee biomechanics after anterior cruciate ligament reconstruction appear to be related with the donor site. PMID- 20356518 TI - [Epidemiological investigation of adult metatarsal fractures]. AB - OBJECTIVE: To investigate retrospectively the adult metatarsal fractures within last five years and analyze their epidemiological characteristics. METHODS: The X ray films taken from January 1, 2003 to December 31, 2007 at department of radiology of Hebei provincial orthopedic hospital were reviewed to screen and classify according to OTA fracture comprehensive classification method. The epidemiological characteristics of adult metatarsal fractures were summarized and analyzed. RESULTS: A total of 1949 adult metatarsal fractures were included. The single and multiple types were 1465 and 484 respectively. The 31-50-yr age group was the largest one with 45.26% of the patients. The fifth metatarsal fracture was the most common metatarsal fracture accounting for 42.45% of the total; 58.37% of metatarsal fractures occurred in proximal metaphysis; 87.61% of multiple metatarsal fractures occurred in adjacent metatarsals; 81-A1 group fracture was the most common metatarsal fracture accounting for 35.42% of the total. CONCLUSION: Epidemiological studies of metatarsal fracture offer aids in the diagnosis and treatment of metatarsal fractures. PMID- 20356519 TI - [Relevant imaging and anatomical measurements of presacral space for axial lumbosacral interbody fusion]. AB - OBJECTIVE: To collect the radiological data of the presacral space for axial lumbosacral interbody fusion (AxiaLIF) and to provide theoretic rationales for research work and clinical application of AxiaLIF in China. METHODS: The distance between inner margin of bilateral anterior sacral foramina at the level of S1 was measured radiographically. The distance between iliac vessels and the midline at the level of S1 was measured on enhanced computed tomography (enhanced-CT). The minimum distances between mesorectum and each sacral level or the center of each sacral vertebra were measured on the median sagittal plane of magnetic resonance imaging in order to measure the lengths of relevant instrumentation and fusion device. RESULTS: The distance between inner margin of bilateral anterior sacral foramina at the level of S1 was found to be 34.7 + or - 3.5 and 32.2 + or - 3.0 mm in Chinese males and females respectively (P < 0.05). There was no statistical significance between the design lengths of sleeve and fusion device. The nearest vessel from sacral intervertebral space at the level of S1 was found to be the bilateral internal iliac vein on enhanced-CT with a distance of 57.6 + or - 5.2 and 70.0 + or - 9.1 mm in males and females respectively (P < 0.05). The distance from mesorectum to the center of vertebral body of S2-S5 was found to be statistically significant between males and females (P < 0.05). CONCLUSION: It is feasible to design suitable instrumentation and fusion device for the Chinese. And a safe operating zone has been designated. PMID- 20356520 TI - [Pedicle screw implanting in the treatment of multi-level lumbar spine fractures]. AB - OBJECTIVE: To review the clinical data of a group of patients with multi-level lumbar spine fractures treated with TSRH-3D pedicle screw system and to investigate the effect and post-operative efficacy of this technique. METHODS: Eighteen patients diagnosed as multi-level lumbar spine fracture were treated with TSRH-3D pedicle screw system. The operations were performed at 4 hours to 2 days after injury and the follow-up period was 15-32 months (mean: 23 months). The X-ray and CT scan were taken both preoperatively and postoperatively. RESULTS: (1) Twelve patients became injured from height falling (67%), 5 from traffic accident (28%) and 1 from crush (5%). (2) The improvement rate of spine motion, back pain and lower extremity pain was 67%, 94% and 78% respectively. (3) Compared with preoperative status, the height of anterior border of vertebra improved by 59.2%, lost by an average of 5.2% (P < 0.01) and the Cobb angle was corrected by 19.5 degrees , lost an average of 5.4 degrees . CONCLUSION: It is feasible to treat the multi-level lumbar spine fractures with TSRH-3D pedicle screw system. And the outcome of reduction and fixation is satisfactory. This technique is excellent at improving the height of injury vertebra, physiological curvature and neural function. It also can relieve lumbocrural pain with a definite postoperative efficacy. PMID- 20356521 TI - [Effect and mechanism of ropivacaine on the isolated human umbilical artery]. AB - OBJECTIVE: To investigation the effect of ropivacaine on the contraction of the isolated human umbilical artery and the mechanisms involved. METHODS: Endothelium denuded human umbilical artery rings obtained from healthy full-term parturients were prepared. Using isometric force transducers and a fluorometer, the effect of ropivacaine in cumulative concentration on the contraction response induced by KCl in the presence or absence of verapamil, or verapamil plus ruthenium red or verapamil plus heparin was observed. Furthermore, the effect of ropivacaine on the contraction response of the artery rings incubated in different concentrations of extracellular Ca(2+) was also observed. RESULTS: Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings: increasing at concentrations of 1.0 x 10(-5) to 1.0 x 10(-4) mol/L and decreasing from 3.0 x 10(-4) to 3.0 x 10(-3) mol/L, which was inhibited by verapamil, or verapamil plus ruthenium red, or verapamil plus heparin. No difference was found between pre-treatment of verapamil, verapamil plus ruthenium red and verapamil plus heparin. Ropivacaine induced no contractile response in Ca(2+)-free solution and a extracellular Ca(2+) dose-dependent increasing contractile response (1.0 x 10(-4) to 3.0 x 10(-2) mol/L). CONCLUSION: Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings. The increase in intracellular Ca(2+) concentrations by the extracellular Ca(2+) influx, not by the release from the sarcoplasmic reticulum, is involved in ropivacaine-induced vasoconstriction of human umbilical artery smooth muscle. PMID- 20356522 TI - [Factors associated with mortality in cryptococcal meningitis]. AB - OBJECTIVE: To investigate factors associated with mortality in non-AIDS patients with cryptococcal meningitis. METHODS: We retrospectively reviewed 154 cases of non-HIV cryptococcal meningitis in a tertiary care hospital in China, from 1997 through 2007. RESULTS: The 1-year attributable mortality was 19.6% (28/143), and overall mortality was 28.7% (41/143). Advanced age (> or = 60 years), delay in diagnosis (> 4 months), hematologic malignancy, solid malignancy, altered mental status (coma, seizure, herniation), and CSF drainage or shunting were factors associated with increased death; factors associated with increased survival were amphotericin B based initial therapy and flucytosine containing therapy. In multivariate analysis, age > or = 60 years, the time from symptom onset to diagnosis > 4 months, coma, cerebral herniation, and non-amphotericin B based initial therapy were independently associated with increased overall mortality; factors independently associated with cause-specific mortality were time from symptom onset to diagnosis > 4 months, cerebral herniation and non-amphotericin B based initial therapy. CONCLUSION: A variety of factors were associated with mortality in non-AIDS cryptococcal meningitis. Amphotericin B based initial treatment was independently correlated to improved 1-year survival. PMID- 20356523 TI - [The diagnosis and therapy of acute upper limbs deep venous thrombosis]. AB - OBJECTIVE: To conclude the experience of diagnosis and therapy, the effect analysis and the prognosis factors of acute upper limbs deep venous thrombosis (ULDVT). METHODS: We retrospectively analyzed the etiological factor, clinical manifestation, diagnosis, therapy and prognosis of 28 patients treated for acute ULDVT admitted in our hospital between 1988 and 2009. The patients were divided into two groups according to the time of admission and management in hospital. Group I, from 1988 to 1998, and group II, from 1999 to 2009. RESULTS: There were 28 patients diagnosed as acute ULDVT, which was 8.1% of lower limbs deep venous thrombosis in synchronization. There were 14 men and 14 women, and the mean age was 46.1 years. 17 patients developed in left upper limbs, and 11 patients developed in right upper limbs. There were 9 patients in group I and 19 in group II. A significant difference was observed between two groups in their risk factors, primary and secondary cause. 8 patients (28.6%) were relevant to venepuncture catheterization, and 13 patients (46.4%) have tumors. There is clear difference between the two groups in the way of primary disease and risk Factors, which means that the probability of ULDVT caused by malignant tumors or other factors in group II is apparently higher than group I, and the prognosis of group II is worse compared with group I. All the patients in the group were made a definite diagnosis by ultrasound, after that our policy were thrombolysis and anticoagulation followed by Warfarin oral administration for 6 months. All the conditions of the patients were well improved, and the symptoms were relieved obviously and discharged. The mean follow-up duration was 2.2 years. 2 recurred, 1 was pulmonary infarction, and 6 was died. CONCLUSION: The incidence of ULDVT is much lower than LLDVT. The motivations are blood hypercoagulable state, such as tumor, vein catheterization etc. The final diagnosis is mostly based on clinical manifestation combined with ultrasound. Thrombolysis, anticoagulation in time have an obvious therapy effect. After that the anticoagulation therapy through oral administration can prevent recurrence. PMID- 20356524 TI - [Enhancement pattern of thyroid carcinoma with contrast-enhanced ultrasound]. AB - OBJECTIVE: To investigate the enhancement pattern of thyroid carcinoma with contrast-enhanced ultrasound (CEUS) for the diagnostic value. METHODS: Thirty-one cases with thirty-five thyroid Occupied were retrospectively reviewed. The final diagnosis was confirmed by biopsy pathology. Contrast agent SonoVue and contrast pulse sequencing (CPS) technique were used in this study. RESULTS: Thirty-five thyroid carcinoma presented three enhancement patterns with CEUS. Type I: twenty three lesions enhanced in a pattern of ring with centripetal fill-in, however, the central part of no contrast agent filling. Type II: five lesions enhanced regularly and homogeneously. Type III: seven lesions enhanced irregularly and homogeneously. Thyroid benign and malignant lesions perfusion time curve, compared to papillary thyroid carcinoma with nodular goiter in the AT, TTP and WT indicators P < 0.05; papillary thyroid carcinoma and thyroid adenoma, compared to WT alone an indicator of P < 0.05. CONCLUSIONS: Identification of the different enhancement patterns of thyroid carcinoma could improve the diagnostic ability of CEUS. PMID- 20356525 TI - [A preliminary study on the correlation between clinical makers with the length of patients' hypertension history]. AB - OBJECTIVE: To investigate the correlation between length of hypertension history with plasma level of A Phospholipids Component with the Similar Solubility of Lyso-Phosphatidic Acid (APCSSLPA or briefly AP). So that to farther understand the changes accompanied with prolongation of hypertension history. METHODS: This is a small cross-sectional study. 170 patients with primary hypertension and 79 normal controls without hypertension history were enrolled. The lengths of case history were recorded and compared with their plasma levels of AP. Similar study were also conducted on other 11 clinical makers as references. RESULTS: AP correlated significantly with the length of hypertension history. Correlation coefficient beta is 0.186, P = 0.015. But AP did not correlated significantly with systolic or diastolic pressure of patients. The age of patients did not correlated with AP either (beta = 0.027, P = 0.71). The patient's number with middle or high level of AP was significantly larger in the group in which hypertension history was 10 years or more, than in the group in which hypertension history was less then 10 years. chi(2) = 6.51, P = 0.012. OR = 2.444, 95%CI = 1.219 - 4.903. However, lysophosphatidic acid and other 10 bio makers which often be used in cerebrovascular and cardiovascular diseases, such as blood lipid, blood sugar, different kinds of lipoprotein and D-dimer etc. did not correlated significantly with hypertension history. CONCLUSION: Comparing with 11 clinical makers, AP was the only one correlated with the length of hypertension history. Our findings suggest: the prolongation of hypertension history may accompanied with increased oxidative damages. The patients with prolonged hypertension history should prevent this possible threaten. Furthermore, AP is a very promising marker with unique worth in cardiovascular and cerebrovascular diseases. PMID- 20356526 TI - [Comparison and superiority of streamlined liner of the pharynx airway to laryngeal mask airway or tracheal tubes for gynecological laparoscopy]. AB - OBJECTIVE: To compare the variations of hemodynamics or respiratory parameters and postoperative complications incidence in gynecological laparoscopy to perform Laryngeal Mask Airway (LMA), Streamlined Liner of the Pharynx Airway (SLIPA) or Tracheal Tube (TT) and to appraise the safety or superiority SLIPA in gynecological laparoscopy. METHODS: 90 patients as ASA I-II grade for gynecological laparoscopy to divide randomly into three groups (n = 30): SLIPA group(S), LMA group(L), TT group(T). Patients were intubated with SLIPA, LMA or TT respectively after general anesthesia induction. Record and count baseline or variable values on heart rate, mean arterial pressure, peak inspiratory pressure, flat inspiratory pressure, airway compliance, airway resistance as pre- and post intubation. To observe intra- and post-complications on backflow or aspiration, airway shifting, oral mucosa damage, cough or expectoration, pharyngodynia, trachyphonia and to appraise patient's comfort as extubation. RESULTS: S or L group is more stable than T on hemodynamic (P < 0.05) during intubation, S group is more stable than L or T group on respiratory parameters (P < 0.05). Intraoperative incidences are significantly lower in S group than L group on backflow or aspiration, airway shifting or oral mucosa damage (P < 0.05), postoperative incidences are significantly lower in S group than L or T group on pharyngodynia, trachyphonia or cough or expectoration (P < 0.05). In addition, extubation comfort degree is better to patient as resuscitation (P < 0.05). CONCLUSIONS: SLIPA are safely or conveniently applicable in gynecological laparoscopy. It impacts little on variations of hemodynamics or respiratory parameters after general anesthesia and reduces intra- or post-operative complications significantly compared to L or T group, increases patient's comfort as extubation. SLIPA is superior to other two on clinical applications. PMID- 20356527 TI - [Long-term results of esophageal motor dysmotility after Heller's myotomy for achalasia]. AB - OBJECTIVE: To investigate the long-term characteristics of both clinical manifestation and esophageal motor disturbance in achalasia patients after Heller's myotomy. METHODS: After 3 to 10 years' follow-up, clinical manifestation, esophageal motor function and 24-hour continuous esophageal pH monitoring in 72 post-operative cases of achalasia were recorded. RESULTS: The mean LES pressure decreased from 44 + or - 12 mm Hg to 10 + or - 5 mm Hg, and the rate of L ES relaxation rised from 49% + or - 20% to 84% + or - 15% (paired t test, P < 0.05). Of 24 cases with choking feeling, 11 had the high LES pressure and dysfunction in two directions and 7 in three. During swallowing, incomplete lower esophageal sphincter relaxation and aperistalsis were detected in all patients. CONCLUSIONS: The long-term characteristics of esophageal function following successfully surgical treatment to patients with Achalasia are: (1) After Heller's myotomy, LESP in at least one direction is lower than the normal standard, while higher in at least one direction. (2) During swallowing, the esophageal rear wall is lack of complete LES relaxation. For patients with choking feeling, complete LES relaxation occurs in 2-3 directions. (3) Due to lack of esophageal peristalsis, food goes through esophagus by gravitation. PMID- 20356529 TI - [Expression of nuclear autoantigenic sperm protein in platinum resistance ovarian cancer cell clones]. AB - OBJECTIVE: To study the expression of NASP in platinum resistance ovarian cancer cell clones (C0C1/DDP). METHODS: The proteins of C0C1 and C0C1/DDP were separated by highly sensitive two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI TOF-MS) to identify the proteins differentially expressed in cisplatin sensitive and cisplatin resistance cell lines. RESULTS: The investigators found a group of the distinct expressed proteins between C0C1 and C0C1/DDP. Among them, NASP was one of the down-regulated proteins by 21% (Student's t-test; P = 0.01). CONCLUSION: The identification of NASP in C0C1/DDP has laid a foundation for future in-depth researches into the mechanisms of ovarian cancer platinum resistance. PMID- 20356528 TI - [Magnetic/luminescent quantum dots bifunctional nanoparticles labeling of rat bone mesenchymal stem cells]. AB - OBJECTIVE: To evaluate the dual-labeling efficiency of magnetic and luminescent quantum dots bifunctional nanoparticles to rat bone mesenchymal stem cells (BMSC). METHODS: Rat BMSC were isolated, purified, and expanded. Magnetic/luminescent bifunctional nanoparticles (Fe(3)O(4)@CdTe@SiO(2)), were prepared by using silicon dioxide (SiO(2)) to encapsulate simultaneously Fe(3)O(4) and CdTe quantum dots. BMSC were incubated with the Fe(3)O(4)@CdTe@SiO(2) nanoparticles which iron concentration was 25 microg/ml. Fluorescence microscope was used to detect the fluorescence of the intracellular nanoparticles. The dual-labeled BMSC with various concentration underwent ex vivo MR imaging with T(1)WI, T(2)WI and T(2)(*)WI sequences. To show the intracellular iron of labeled cells, prussian blue stain was performed. Spectrophotometer was used to detect the iron concentration in the cells. RESULTS: Intracellular red fluorescence of Fe(3)O(4)@CdTe@SiO(2) can be observed via fluorescent microscopy. Rat BMSC could be effectively dual-labeled with approximately 90% efficiency. The MR images with T(2)WI and T(2)(*)WI sequences, especially with T(2)(*)WI sequence, showed that the signals of the dual-labeled BMSC were lower than those of the unlabeled cells. Cellular total iron is 14.05 + or - 4.15 pg per cell. Iron containing intracytoplasmic vesicles could be observed with Prussian blue staining. CONCLUSION: Rat BMSC can be dual-labeled successfully with Fe(3)O(4)@CdTe@SiO(2) magnetic/luminescent bifunctional nanoparticles successfully, and might serve as a tool for magnetic resonance imaging and in vivo optical imaging. PMID- 20356530 TI - [Attach importance to Merwe disease in percutaneous nephrolithotomy]. PMID- 20356531 TI - [General practice medical education should step to speedway]. PMID- 20356532 TI - [Clinical implication of stone culture in percutaneous nephrolithotomy]. AB - OBJECTIVE: To evaluate the correlation between stone culture and SIRS, ascertain the clinical implication of stone culture in PCNL. METHODS: Clinical data of 66 patients who underwent PCNL in our department were analyzed retrospectively. Eight risk factors including stone culture + drug sensitivity, urine culture + drug sensitivity, age, gender, prophylactic antibiotics, stone volume, operative time and the number of tract. Multiple statistics methods were used for analysis to evaluate the impact of SIRS, and compare the difference between stone culture and urine culture. RESULTS: Univariate analysis and Multivariate logistic regression model showed that positive stone culture was the risk factor of SIRS (P < 0.05). Positive stone culture was found in 48.48% patients, which was higher than that of urine culture (30.30%). Fourteen patients (66.67%) of 21 postoperative SIRS patients were prescribed antibiotics according to the stone culture result. And all of them recovered unevenly without developing septic shock or MODS. CONCLUSIONS: Positive stone culture is the important risk factor of post-PCNL SIRS. Stone culture is better than urine culture in directing postoperative antibiotics prescripsion and should be routinely used. PMID- 20356533 TI - [Effects of irrigating fluid absorption in percutaneous nephrolithotripsy]. AB - OBJECTIVE: To determine the hemodynamic status, fluid-electrolyte changes and complications associated with irrigation time in percutaneous nephrolithotripsy. METHODS: A total of 68 renal calculi patients (31 males and 37 females) were recruited. The lateral recumbent percutaneous nephrolithotripsy was operated with Ho laser under ultrasonic guidance. 0.9% NaCI was used as perfusion fluid. The following items were recorded: mean arterial blood pressure (MAP), heart rate, central venous pressure (CVP), hemoglobin, sodium, potassium and chloride; perfusion time during operation; peri-operative and post-operative complications. RESULTS: (1) Peri-operative and post-operative conditions: the average operative time was 83.1 +/- 22.21 minutes. Two cases stopped because of bleeding after puncture and the tube of stoma was placed for stone clearance of the second time. There was more bleeding in 11 patients, but the operations were continued with blood transfusion and close monitoring. Two operations ceased because of a premunition of congestive heart failure. Nine patients needed post-operative blood transfusion and 18 had a post-operative fever. One patient bled in and around the tube and had a peri-renal infection a week later. (2) Changes of observation parameters: there was no significant difference in CVP, heart rate, hemoglobin, sodium, potassium and chloride (P > 0.05). The post-perfusion value of MAP increased (P < 0.05) especially in the cases of more bleeding and long time of irrigation. Peri-operative and post-operative injection of furosemide could reduce the CVP value. The average irrigation time in the fever group was longer than the non-fever group (P < 0.05) and the CVP value of the fever group was higher than the non-fever group (P < 0.05). CONCLUSION: Low pressure and short time of perfusion are safe in clinical practice. Congestive heart failure after the perfusion and the occurrence of post-operative infections are difficult to avoid when there are a long time of irrigation and more bleeding during operation. PMID- 20356534 TI - [Clinical comparative study of five minimally invasive surgeries for upper urinary tract calculi]. AB - OBJECTIVE: To compare the efficacy of minimally invasive percutaneous nephrolithotomy (PCNL), ureteroscopes supple of lens of lithotrity (URSf), ureter forcedly of lens of lithotrity (URSnf), laparoscopic ureterolithotomy and retroperitoneal laparoscopic ureterolithotomy and to explore the best methods and indications for treating the complex upper urinary tract calculi. METHODS: The distribution of cases was as follows: URSnf (n = 869), URSf (n = 56), MPCNL (n = 57), laparoscopic ureterolithotomy (n = 9) and retroperitoneal laparoscopic ureterolithotomy (n = 80). RESULTS: A successful outcome was obtained in URSnf (n = 856), URSf (n = 51), MPCNL (n = 46), laparoscopic ureterolithotomy (n = 9) and retroperitoneal laparoscopic ureterolithotomy (n = 75). And the success rate was 98.50%, 91.07%, 80.70%, 100% and 93.75% respectively. Five cases (0.47%) failed and there were not severe complication in all surgery groups. CONCLUSION: If a good indication of each approach is mastered, 5 minimally invasive are relatively safe and highly effective for most patients with complex upper urinary tract calculi. PMID- 20356535 TI - [Relationship of adipocyte fatty acid-binding protein to adiponectin ratio with femoral intima-media thickness and endothelium-dependent vasodilation in patients with newly-diagnosed type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the relationship between plasma adipocyte fatty acid binding protein (A-FABP), adiponectin (APN) levels and A-FABP/APN ratio with femoral intima-media thickness (FA-IMT) and endothelium-dependent vasodilation in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Plasma A FABP and APN in 133 patients with newly diagnosed T2DM were measured by enzyme linked immunosorbent assays. FA-IMT, endothelium-dependent and independent vasodilation of brachial artery was measured by high-resolution vascular ultrasound. Upper quartile of FA-IMT was regarded as a criterion of elevated FA IMT, defined as early atherosclerosis (AS). The patients were subdivided into low FA-IMT group (FA-IMT < 0.60 mm, n = 34), middle FA-IMT group (0.60 mm /= 0.80 mm, n = 33). RESULTS: Plasma A-FABP/APN ratio was higher in early AS group than in low IMT control group [A-FABP/APN x 1000, 3.9(2.8 approximately 6.1) vs 2.9(1.8 approximately 5.7), P < 0.05]. FA-IMT correlated positively with plasma A-FABP/APN ratio (r = 0.216, P = 0.006) and negatively with APN (r = -0.179, P = 0.020). After adjusted for age, gender and BMI, FA-IMT still correlated positively with plasma A-FABP/APN ratio (r = 0.217, P = 0.007) and negatively with APN (r = -0.172, P = 0.026). Endothelium-dependent vasodilation correlated negatively with plasma A-FABP/APN ratio (r = -0.166, P = 0.028). After adjusted for age, gender and BMI, endothelium-dependent vasodilation still correlated negatively with plasma A-FABP/APN ratio (r = 0.153, P = 0.042). CONCLUSION: Plasma A-FABP/APN ratio is closely associated with FA-IMT and endothelium-dependent vasodilation. Plasma A-FABP/APN ratio may be a better clinical marker of AS and endothelial dysfunction than A-FABP or APN alone in patients with newly diagnosed T2DM. PMID- 20356536 TI - [Killer cell immunoglobin-like receptor and its ligand gene polymorphisms in Hunan Han patients with type 1 diabetes]. AB - OBJECTIVE: To investigate the association of Killer cell immunoglobin-like receptor (KIR) gene and KIRs'ligand (HLA-C) gene polymorphisms with type 1 diabetes (T1DM). METHODS: Using polymerase chain reaction-sequence specific primer (PCR-SSP) to detect KIR and HLA-C genotype in 180 T1DM patients and 199 healthy controls from Hunan Han population. RESULTS: (1) The frequencies of KIR 2DL1 (98.9% vs 92.0%, OR = 7.78, P = 0.002), 3DL1 (94.3% vs 86.4%, OR = 2.67, P = 0.009) and 2DS4 (83.9% vs 70.9%, OR = 2.14, P = 0.003) were significantly higher in T1DM patients than those in the controls. (2) There were no differences in the frequencies of HLA-C1 and HLA-C2 between the patients and the controls, but the frequency of HLAC1+/C2+ (3.9% vs 9.6%, OR = 0.38, P = 0.03) was significantly lower in the T1DM patients. (3) The combination KIR2DL1-/HLA-C2-(0.6% vs 6.0%, OR = 0.087, P = 0.003) and KIR 2DS1-/HLA-C2-(53.3% vs 64.8%, OR = 0.62, P = 0.023) was significantly lower in the T1DM patients. CONCLUSION: The KIR gene polymorphism and KIR/HLA-C gene compatibility are associated with T1DM. PMID- 20356537 TI - [Expression of human leucocyte antigen G in peripheral blood of kidney transplantation recipients]. AB - OBJECTIVE: To investigate the expression of non-classical major histocompatibility complex (MHC)-I molecule, human leucocyte antigen (HLA) G, including membrane-bound HLA-G (mHLA-G), intracellular HLA-G (iHLA-G) and soluble HLA-G (sHLA-G), in peripheral blood of surviving kidney transplantation recipients and understand the relevance between HLA-G and the function of transplanted organ, as well as the onset of acute rejection. METHODS: A longitudinal study was performed on 175 kidney transplantation recipients. Three groups were involved in this study, including acute rejection group (n = 36), function stable group (n = 139) and healthy control group (n = 30). The expression of mHLA-G1 and iHLA-G1 in the T lymphocytes of peripheral blood was detected by flow cytometry analysis and the sHLA-G5 level detected by ELISA. RESULTS: The average rate of CD4(+)mHLA-G1(+), CD8(+)mHLA-G1(+), CD4(+)iHLA G1(+), CD8(+)iHLA-G1(+) in T lymphocytes of healthy control group was 0.43% +/- 0.19%, 1.23% +/- 0.41%, 27% +/- 13% and 36% +/- 14% respectively. That of acute rejection group was 0.57% +/- 0.34%, 1.31% +/- 0.56%, 26% +/- 8% and 37% +/- 17%; that of function stable group was 0.61% +/- 0.43%, 1.39% +/- 0.47%, 26% +/- 9% and 37% +/- 17% respectively. There was no significant difference among the three groups (all P > 0.05). The average of sHLA-G5 levels in plasma of control group was (25 +/- 14) ng/ml, acute rejection group (24 +/- 15) ng/ml (pre-operative) and (34 +/- 21) ng/ml (post-operative), function stable group (25 +/- 11) ng/ml (pre-operative) and (56 +/- 32) ng/ml (post-operative). There was no significant difference among the three groups (pre-operative, P > 0.05). The average of sHLA G5 levels in plasma of function stable group was higher than that of acute rejection group (post-operative, P < 0.05). CONCLUSION: There is a subset of CD4(+)HLA-G1(+) and CD8(+)HLA-G1(+)T lymphocytes with low percentage in peripheral blood of those surviving kidney transplantation recipients. The expressions of mHLA-G1 and iHLA-G1 have no relevance with the onset of acute rejection. sHLA-G5 is correlated with acute rejection in peripheral blood of surviving transplantation recipients. PMID- 20356538 TI - [Clinical significance of positive sputum culture for filamentous fungi]. AB - OBJECTIVE: To investigate the clinical significance of positive sputum culture for filamentous fungi. METHODS: The medical data of 140 patients positive for filamentous fungi in sputum culture at Peking Union Medical College Hospital were reviewed retrospectively. Based on the diagnostic criteria by European Organization for Research and Treatment of Cancer/Mycoses Study Group, invasive pulmonary fungal infection (IPFI) was diagnosed. The clinical characteristics of cases with and without IPFI were analyzed respectively. RESULTS: Among all 140 cases positive for filamentous fungi in sputum culture, only 22 cases could be diagnosed as IPFI. Two of 22 IPFI cases were confirmed by post-operative pathology, 1 case was confirmed by positive blood culture for filamentous fungi and the remaining 19 cases were diagnosed clinically according to the nature of hosts, characteristics of pulmonary infections and microbiological evidence (positive sputum culture for filamentous fungi, 2 - 5 times for each case). Most of etiological fungi in IPFI patients belonged to Aspergillus. And the identity of isolated fungal strain was mostly one strain for each patient. In IPFI group, patients who had been treated with broad-spectrum antibiotics (100%), steroids (13, 59.1%) or immunosuppressant (7, 31.8%) or who had pulmonary X-ray imaging changes (100%), primary diseases (21, 95.5%), hypoalbuminemia (18, 81.8%) or hemoptysis (10, 45.5%), were significantly more than those in non-IPFI group (66.9%, 34.7%, 18.6%, 79.7%, 72.0%, 45.8% and 4.2% respectively; P < 0.05 for each item). In IPFI group, itraconazole, amphotericin B and/or voriconazole were administrated, 8 patients (36.4%) were cured and 14 patients (63.6%) passed away. In non-IPFI group, the patients were treated with antibiotics, fluconazole, anti tuberculosis, steroids or combined with immunosuppressant, chemotherapy or bronchoalveolar lavage; 96 cases (81.4%) were cured or showed improvement, and 22 cases (18.6%) died or gave up further treatment. CONCLUSIONS: The clinical significance of positive sputum culture for filamentous fungi are associated with the times of positive culture, the number and species of isolated fungal strains. Meanwhile it is important to determine whether there is IPFI according to the nature and clinical characteristics of patients. PMID- 20356540 TI - [The study of relationship between platelet function and thrombus in patients with essential thrombocythaemia]. AB - OBJECTIVE: To observe the influence of the plasma thromboxane B2 (TXB2), 6-keto PGF1alpha, CD62P and PAC-1 and Thrombus in patients with primary thrombocytosis (ET). To observe the effect of sodium ozagrel to prevent and treat thrombosis in patients with ET. METHODS: The subjects including 48 patients with ET. All patients were measured the plasma TXB2, 6-keto-PGF1alpha, CD62P and PAC-1 before and after treatment with or without sodium ozagrel. RESULTS: The plasma levels of CD62P, PAC-1, TXB2, 6-keto-PGF1alpha and TXA2/PGI2 in the patients with ET were significantly higher than the normal people (P < 0.01). The levels of CD62P, PAC 1, TXB2, TXB2/6-keto-PGF1alpha in patients with treatment of sodium ozagrel were higher than patients without treatment of sodium ozagrel (P < 0.01). The plasma levels of CD62P, PAC-1 and TXA2/PGI2 in patients with treatment of sodium ozagrel and that in normal people had no significant distinction (P < 0.01). All the index of conventional therapy group were higher than normal people (P < 0.01) but had no significant distinction with the patients before conventional treating. The incidence of thrombus in patients treated with sodium ozagrel was lower than patients treated without sodium ozagrel (P < 0.05). CONCLUSION: With the treatment of sodium ozagrel in patients with ET, the CD62P, PAC-1, TXB2 and TXA2/PGI2 of plasma could be decreased. And the incidence of thrombus was decreased. PMID- 20356541 TI - [Diagnosis and treatment of sarcomatoid renal cell carcinoma]. AB - OBJECTIVE: To study the clinical diagnosis and treatment of sarcomatoid renal cell carcinoma, and to analyze the connection of prognosis with therapy. METHODS: 10 cases with sarcomatoid renal cell carcinoma from 1997 - 2007 in our hospital were analyzed, and the related literatures were reviewed. RESULTS: All patients were performed with operation, and pathologically diagnosed as sarcomatoid renal cell carcinoma. Cases with metastasis were performed with chemical therapy, biological therapy or radiotherapy after operation. Clinical stage (TNM) of 10 cases is T1N0M0 1 case, T2N0M0 3 cases, T3N0M0 1 case, T4N0M0 1 case, T2N0M1 3 cases, T4N0M1 1 case. 60% (6/10) of patients were diagnosed with metastasis or diffusion. In these 6 cases, 4 cases were diagnosed with pulmonary metastasis, 1 with brain metastasis, and 1 with osseous metastasis, and 1 with inferior vena cava tumor thrombus. The average life span of all 10 cases was 17 months, and cases with advanced stage was 8 months. Otherwise, the average survival time of cases with earlier stage was 30 months, and it was 21 months from diagnosis to metastasis. CONCLUSION: Sarcomatoid renal cell carcinoma is a special type of renal cell carcinoma with features of high malignant and rapid progress. It is clinical rare and with bad prognosis. Operation is the first choice for the therapy, the effect of radiotherapy or chemical therapy is not obviously. The lung is main position for metastasis. Early diagnosis and treatment are effective to prolong the life span of patients, and the new therapy may be more important. PMID- 20356539 TI - [Clinical study of comparing comorbidity between depression and neurological disorder with depressive disorder]. AB - OBJECTIVE: To compare the clinical traits in comorbidity between depression and neurological disorder with depressive disorder and explore the characteristic of the outpatients with neurological disorder comorbidity in depression. METHODS: According to Diagnosis and Statistic Manual for Mental Disorder-IV (DSM-IV) criteria, outpatients were diagnosed as depressive disorder at Departments of Neurology and Psychology. We used HAMD-17 scale to evaluate the patient's severity. RESULTS: There was no statistical difference in severity of depression in two groups. But the clinical traits showed significant differences between two outpatient groups: the outpatients with neurological disorder comorbidity in depression were elder, had more somatic disorders and a higher retard symptom factor score while the other are relative younger, have less physical disorders and higher the core symptom factor score on the other hand. CONCLUSION: The patients of comorbidity between depression and neurological disorders have unique clinical traits. Thus it will be helpful to improve the identification of diagnosis and choose an appropriate treatment if we know the differences well. PMID- 20356542 TI - [Cardioprotective effect and mechanism of post-infarction ventricular remodeling after self-assembling peptide and thermosensitive hydrogel implantation in rat myocardial infarction model]. AB - OBJECTIVE: To compare the cardioprotective effect of self-assembling peptide (RAD16-II) and thermosensitive hydrogel DPHP (Dex-PCL-HEMA/PNIPAAm) and investigate the optimal property of hydrogel for the treatment of myocardial infarction (MI). METHODS: MI model was induced by left anterior descending (LAD) coronary artery ligation in SD rats. The animals were randomized into three groups to receive RAD16-II hydrogel (n = 15), DPHP hydrogel (n = 15) or PBS (phosphate buffered saline; control group n = 15); sham-operated rats (n = 10), a suture was tied loosely around left coronary artery without ligating it. At Day 20 post-MI, left ventricle function was evaluated by echocardiography and cardiac catheter. Masson's trichrome was used for histological examination; anti-alpha smooth muscle antigen (alpha-SMA) was applied to label the neovasculature formation in infarct area. RESULTS: The rats receiving DPHP hydrogel showed a significantly smaller left ventricle end diastolic diameter (LVEDd) and higher levels of left ventricle fraction shortening (LVFS) and left ventricle end systolic pressure (LVESP) than the rats in RAD16-II group [LVEDd (7.9 +/- 0.9) mm vs (8.9 +/- 0.8) mm]; [LVFS (25.4 +/- 5.1)% vs (21.9 +/- 2.9)%; LVESP (114.0 +/- 7.6) mm Hg vs (99.1 +/- 9.6) mm Hg; P < 0.05]. Histological examination showed uncompleted degraded hydrogel in infarct area of DPHP group but not in RAD16-II group. The animals receiving DPHP hydrogel demonstrated significantly a smaller infarct size, a higher infarct wall thickness and a lower vessel density in infarct than the animals receiving RAD16-II hydrogel (P < 0.05). CONCLUSION: DPHP hydrogel implantation further inhibits the post-MI ventricle remodeling than RAD16-II hydrogel implantation. The mechanism is not correlated with the vascular density in infarct area. PMID- 20356543 TI - [Research on the mechanism of ginsenoside Rh2 reversing the resistance of lung adenocarcinoma cells to cisplatin]. AB - OBJECTIVE: To explore the mechanism of ginsenoside Rh2 in reversing the resistance of lung adenocarcinoma cells to cisplatin. METHODS: In the Rh2, DDP and DDP + Rh2 group A549DDP cells were treated with Rh2, cisplatin, cisplatin + Rh2 respectively for 48 hours. In the control group the A549DDP cells were not treated with any kind of drugs. The state of mitochondrial permeability transition pore (PTP) was evaluated by ultra violate spectrofluorometer. Concentration of calcium in cells, membrane potential of mitochondrion and apoptosis cells were determined by flow cytometry. The expression of cyt-c and Caspase-3 was estimated by Western blots. Cellular shapes were observed by fluorescent microscopy. RESULTS: The concentrations of calcium were similar among the former three groups, but was obviously increased in the Rh2 + DDP group (t = 22.47, P < 0.01). A(540) of mitochondrion among the former three groups were not different, but decreased significantly in the Rh2 + DDP group (t = 8.21, P < 0.01). The membrane potentials of mitochondrion showed no difference in the former groups, that was remarkably lower in the Rh2 + DDP group than in the control group (chi(2) = 46.01, P < 0.01). There was little expression of cty-c and Caspase-3 in the former groups, but high expression of those in the Rh2 + DDP group. Fluorescence was distributed equally on the cells nucleus in the former groups. In the Rh2 + DDP group many cell nucleus shrank or were distorted. The apoptosis rate of the cells was 6.32%, 7.24%, 7.41% and 21.96% in the four groups respectively. Which in Rh2 + DDP group was higher than that in the control group (t = 10.92, P < 0.05). CONCLUSIONS: The effect of ginsenoside Rh2 reversing resistance of lung adenocarcinoma A549DDP cells to cisplatin can be performed by apoptotic mitochondria pathway. PMID- 20356544 TI - [Manganese enhanced magnetic resonance imaging for tracing corticospinal tracts in rat brain using 7.0 T MRI]. AB - OBJECTIVE: To investigate the methods of manganese enhanced magnetic resonance imaging in 7.0 T magnetic field for tracing corticospinal tract in rat brain in vivo. METHODS: 0.4 microl volume of 1 mol/L aqueous solution of MnCl(2) was injected into the primary motor cortex of 9 SD rats under stereotaxis. MRI studies were performed for tracing corticospinal tract and other coherent nerve tracts before injection and 24 hours, 48 hours, 72 hours, 7 days after injection respectively using 7.0T Micro-MRI. RESULTS: Corticospinal tract was visualized perfectly from primary motor cortex, thalamus, cerebral peduncle to pons at different time points after Mn(2+) administration, and the best contrast was achieved after 24-48 h. At the same time, a small quantity of Mn(2+) reached the opposite somatosensory cortex through the corpus callosum. CONCLUSION: Manganese enhanced MRI visualizes perfectly the transport of Mn(2+) through axoplasmic flow in corticospinal tracts. This method may be used to investigate the change of corticospinal tract and the functional connectivity between two sides of hemisphere in rat brain. PMID- 20356545 TI - [Strenuous explorations of biological therapeutics for the degenerative changes of intervertebral disc]. PMID- 20356546 TI - [Association study of Trp2 allele polymorphism with degenerative disc disease in a Chinese Han nationality]. AB - OBJECTIVE: To investigate the association between Trp2 allele polymorphism with degenerative disc disease (DDD) in a Chinese Han population. METHODS: A total of 125 DDD patients (58 males and 67 females, 51.8 +/- 7.6 years old), and 125 controls matched in sex and age (63 males and 62 females, 45.3 +/- 8.3 years old) were recruited in the case-control study. Their peripheral blood samples were collected for DNA isolation. Based on NCBI genebank, the corresponding single nucleotide polymorphisms (snp)-SNP1 (rs7533552) and SNP2 (rs2077871) were identified. Hardy-Weinberg equilibrium was analyzed both in case and control groups. Then the case group was classified into different clinical phenotypes according to severity of degeneration, sole or multi-disc degeneration and different affected discs. Genotyping of all selected SNPs was performed by SNP stream technology. The association analysis between phenotypes and SNPs was conducted. Pairwise linkage disequilibrium was calculated in control population using Haploview 4.0 software. RESULTS: SNP1 (rs7533552), SNP2 (rs2077871) and corresponding SNP of Trp2 allele were gentyped and both polymorphisms distributed in line with Hardy-Weinberg equilibrium in case and control groups. Allelic frequency of SNP1A, SNP1G, SNP2C and SNP2T (42%, 47%, 88% and 90% respectively) of case group were not significantly different from those of control group (48%, 53%, 88% and 10% respectively, all P > 0.05). Genotypic frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2CC, SNP2CT and SNP2TT in case group were not significantly different from those of control group (all P > 0.05). However there was an association with genotypic frequencies of SNP2 and severity of disc degeneration (chi(2) = 6.920, P = 0.031). CONCLUSION: Trp2 allele is one of risk factors for the development and severity of DDD in a Chinese Han population. PMID- 20356547 TI - [Finite element analysis of screw in percutaneous axial lumbosacral interbody fusion]. AB - OBJECTIVE: To establish a 3D finite element model of L5/S1 motion segment with percutaneous axial lumbosacral interbody fusion (AxiaLIF) screw and conduct a preliminary analysis of biomechanical stress. METHODS: The titanium screw was implanted in L5 and S1 vertebral body. Solid model was established by CAD software according to the actual dimensions of screw. Then computer graphics were obtained from iges format and imported into the finite element analysis software to establish the finite element model. With the aid of Mechanical Virtual Human of China, a 3D finite element model of L5/S1 motion segment with AxiaLIF screw was established. Vertical compression, torque moment and bending moment were loaded respectively on the upper surface of L5 vertebrae to simulate the load stress in human body. Stress distribution of screw was obtained. RESULTS: Generally stress values were relatively low. Peak stresses of screw under three loading conditions were 175.334 Mpa, 183.765 Mpa and 146.237 Mpa respectively. Stress value was relatively high at the central part of interbody fusion. And all the highest values were localized at the first thread below the central part. Result of comparison between three conditions: torque load was the highest, followed by vertical load and lateral bending. CONCLUSION: Percutaneous axial lumbosacral screw can meet the normal loading conditions. Further clinical applications are recommended. PMID- 20356548 TI - [Preliminary study on differential expression of plasma proteins of patients with Takayasu's arteritis in different stage]. AB - OBJECTIVES: To investigate differential expression of plasma proteins of patients with Takayasu's arteritis to screen disease-related or phase-related proteins or biomarkers. METHODS: From March, 2005 to January, 2006, Plasma of 20 patients with acute Takayasu's arteritis, 20 patients with chronic Takayasu's arteritis, and 20 healthy people as control were collected. Plasma proteins were profiled by two-dimensional electrophoresis. Spots of differential expression were screened by computerized map analysis and identified by matrix assisted laser desorption/ionization time of flight-mass spectrometry. Circulation levels of parts of differential expression proteins were investigated by Elisa in each subject. RESULTS: Fourteen differential expression proteins were identified, including serum amyloid A, serum amyloid P, fibrinogen, complement C3c, C7, C4 binding protein, factor H related protein-1, immunoglobin, alpha-acid glycoprotein, RAG1 protein, alpha1-microglobin, apolipoprotein A-I, A-IV, transthyretin, haptoglobin. Proteins related to acute and chronic phase were serum amyloid A, fibrinogen, transthyretin, haptoglobin; Circulation levels of Serum amyloid A (SAA) and Complement C4 binding protein (C4BP) were significantly increased in active TA patients comparing to that in inactive TA patients and in controls (SAA: 95.9 vs 49.2, P = 0.009 and 23.9 mg/L, P = 0.001, respectively; C4BP: 88.5 vs 61.7, P = 0.023 and 32.6 mg/L, P < 0.001, respectively). CONCLUSIONS: Acute phase proteins and immune proteins may possible be markers for diagnosis and activity of Takayasu's arteritis, Complement activity, complement modulation protein and antibody production may be involved in immune mechanism of Takayasu's arteritis. Further study of these proteins may be helpful to elucidate the pathologic mechanism of Takayasu's arteritis. PMID- 20356549 TI - [Distribution and evaluation of emergent cases of elderly in vascular surgery]. AB - OBJECTIVE: To find out the distribution of emergent cases of elderly in vascular surgery and to evaluate the complications in peri-operation. METHODS: We retrospectively analyzed all the vascular emergency operations over 60 years old from Jan. 2006 to Oct. 2008 in Peking Union Medical College Hospital. RESULTS: The emergency operations were increased by 30% annually. The concomitant diseases in patients over the age of 60 are higher than those below 60, in which cardiac diseases included valvular disease of heart, cerebrovascular disease and hypertension are most common. Meanwhile there is no significant in complications during peri-operation between patients over sixties and below sixties. CONCLUSION: The evaluation before operation and treatment of concomitant diseases in elderly patients should be done in ahead perfectly in order to reduce the complications during perioperation. PMID- 20356550 TI - [Low dose contrast-enhanced 4D DSA with the 320-detector row computed tomography scanner for post-operative evaluation of the hepatic artery complications after liver transplantation]. AB - OBJECTIVE: To evaluate the value of low-dose contrast-enhanced 4D DSA acquired from 320-detector row CT on the diagnosis of the hepatic artery complications after liver transplantation. METHODS: 320-detector row CT were performed in fifth patients with liver dynamic enhanced using volume CT body-perfusion protocol, hepatic artery phase images obtained after intravenous injection of 50 ml of contrast at a rate of 6 ml/s were acquired based on 4D DSA. The time-density curve (TDC) of the hepatic artery was delineated. The time to peak, peak contrast enhancement were recorded. The data of artery phase were sent to workstation to reconstruct the hepatic artery with VR, MIP and MPR. RESULTS: The delay mean time and the peak CT value of hepatic artery was 20 (10.0 - 24.2) s and 373 (310 - 440) HU; 4D DSA revealed hepatic artery pseudo-aneurysm (n = 2), and hepatic artery mild stenosis (n = 3), moderate stenosis (n = 4), severe stenosis (n = 1) and occlusion (n = 1). Compensatory circulation was seen in 2 cases. 4 patients were appeared segmental stenosis and hepatoportal arteriovenous fistulas (HPAVF). Hepatic arterial branch are decreased and opened in 9 cases and 4 cases. 4D DSA also displayed other signs including hepatic hemangioma and the splenic artery aneurysms (SAA) and ectasi (n = 1), donor-recipient hepatic artery mismatch (n = 3). CONCLUSION: 4D DSA provided a safe, noninvasive and accurate method for guiding the diagnosis of hepatic artery complication and play an effective role after liver transplantation. PMID- 20356551 TI - [Experimental study on sensory gating in generalized anxiety and obsessive compulsive disorders]. AB - OBJECTIVE: To observe the characteristics of sensory gating P50 in generalized anxiety disorder (GAD) and in obsessive compulsive disorder (OCD) patients. METHODS: Auditory evoked potentials P50 were recorded in 41 GAD patients, 69 OCD patients and in 58 normal controls by the conditioning/testing paradigm presented with auditory double clicks stimuli, using American Nicolet Bravo instrument. RESULTS: (1) No significant differences was found in latencies of S1-P50 and S2 P50 among these three groups (P > 0.05). (2) Significant differences were found in indices of S1-P50 amplitudes (NC: 6 +/- 3, GAD: 3 +/- 2, OCD: 5 +/- 3, P < 0.01), S2-P50 amplitudes (NC: 2 +/- 1, GAD: 4 +/- 1, OCD: 2 +/- 1, P < 0.01), S2/S1, S1-S2 and 100(1-S2/S1). (3) Compared with NC, GAD and OCD patients showed a decreased S1-P50 amplitude and OCD patients also showed an increased S2-P50 amplitude. (4) P50 inhibition significantly decreased in GAD and OCD patients. The values of S2/S1 ratio were 39% +/- 22% in NC, 50% +/- 29% in GAD and 88% +/- 42% in OCD (P < 0.01). (5) Both S1-S2 and 100 (1-S2/S1) decreased in GAD and OCD patients (NC: 3 +/- 2, 61 +/- 22; OCD: 1 +/- 1, 15 +/- 22; GAD: 3 +/- 3, 50 +/- 29. P < 0.01). (6) Compared with GAD, OCD patients showed a lower S2/S1 ratio (P < 0.01) and a higher value of S1-S2 (P < 0.01) and 100 (1-S2/S1) (P < 0.01). CONCLUSION: The anxiety disorder patients has sensory gating deficits. The inhibition deficit can be measured by auditory evoked potential P50. And S2/S1 ratio, S1-S2 and 100(1-S2/S1) may be biological markers of GAD and OCD patients. PMID- 20356552 TI - [Differential neuronal firing in globus pallidus internus of patients with Parkinson's disease and dystonia]. AB - OBJECTIVE: To explore the neuronal activity in globus pallidus internus in patients with Parkinson's disease (PD) and dystonia. METHODS: Thirteen patients with Parkinson's disease and eight with dystonia undergoing stereotactic surgery of globus pallidus internus were studied. Microrecording in globus pallidus internus and electromyography on contralateral limbs to surgery were simultaneously performed. Single unit analysis, interspike intervals (ISI) and coefficient of variation of ISI were performed. ANOVA and Student t-test were employed to compare neuronal firing in globus pallidus internus between two patient groups. RESULTS: One hundred and eight neurons were identified from PD patients, including 19.4% tremor-related neuronal activity, 55.6% neurons with tonic firing and 25.0% neurons with irregular discharge. Further analysis revealed that neurons with tonic firing had a mean firing rate of (103.7 +/- 25.5) Hz; neurons with irregular discharge had a mean firing rate of (63.4 +/- 16.1) Hz. Forty-five neurons were identified from patients with dystonia, including 37.8% neurons with tonic firing and 62.2% neurons with irregular discharge. Further analysis showed that neurons with tonic firing had a mean firing rate of (50.2 +/- 19.1) Hz; neurons with irregular discharge had a mean firing rate of (28.5 +/- 10.5) Hz. ANOVA showed that a significance of firing rate of tonic firing and irregular discharge in globus pallidus internus was reached between two patient groups (P < 0.001). The mean firing rate of two patterns of neuronal activity in PD were significantly higher than those in dystonia (Bonferroni test, both P < 0.05). CONCLUSION: The data support the current view that an increased neuronal firing rate in globus pallidus internus is associated with PD whereas a decreased neuronal firing rate is associated with dystonia. PMID- 20356553 TI - [Clinical features of preeclampsia-eclampsia patients with reversible posterior leukoencephalopathy syndrome]. AB - OBJECTIVE: To investigate the clinical features and specific characteristics of magnetic resonance image (MRI) in preeclampsia-eclampsia patients with reversible posterior leukoencephalopathy syndrome (RPLS). METHODS: The investigators analyzed the combined clinical, laboratory and neuroradiographic features of 20 preeclampsia-eclampsia patients with RPLS and 15 preeclampsia-eclampsia controls with normal MRI findings. RESULTS: Patients with RPLS had more tendency to have headache, seizure, visual disturbance, confusion and altered mental status than controls. Neuroimaging showed diffuse edema predominantly in posterior cerebral white matter bilaterally. Clinical features and neuroradiological alterations disappeared after appropriate treatments were started. Twenty RPLS patients had a significantly higher level of uric acid (442 +/- 77 mmol/L) than those without RPLS (350 +/- 88 mmol/L) (P < 0.05). However no difference was observed for other indices. CONCLUSION: Preeclampsia-eclampsia patients with RPLS have typical clinical and imaging findings, and the syndrome is reversible with appropriate treatment. Perhaps endothelial damage is related to the pathogenesis of RPLS. Monitoring the level of uric acid in patients with preeclampsia-eclampsia is of vital significance to discover RPLS in an early stage. PMID- 20356554 TI - [Anterior cruciate ligament reconstruction using periosteum wrapped autologous hamstring tendons: clinical research]. AB - OBJECTIVE: To develop a surgical technique using a periosteal flap wrapped autologous hamstring tendons in ACL reconstruction and to examine its short-term outcome. METHODS: A total of 110 patients (110 knees) were included. The experimental group (n = 52) received ACL reconstruction with hamstring tendons wrapped in periosteum. In the other 58 patients, ACL was reconstructed with autologous hamstring tendons. The mean post-operative follow-up was 19 (12 - 25) months. All patients were assessed at 12 months post-operation. The parameters of efficacy evaluation included IKDC score, Tegner score, modified HSS score, KT 1000 arthrometer reading and a radiographic assessment using anteroposterior and lateral radiographs. The incidence of femoral and tibial bone tunnel enlargement between two groups was compared with chi(2) test. RESULTS: Clinical outcomes in experimental group (periosteum-wrapped grafts) were dependent on the wrap-up of periosteum, bone tunnel, graft fixation and postoperative rehabilitation. The good or excellent outcomes were reported in approximately 90% of the experimental group. And 44 patients showed normal or nearly normal knee function according to IKDC criteria. KT-1000 tests showed an average maximal manual side-to-side difference of 1.7 +/- 1.1 mm. Forty patients showed the outcomes of KT-1000, Lachman's knee ligament test and pivot-shift testing. The evaluation of the level of activity using the Tegner score revealed that 40 patients regained their pre injury activity level. And 44 patients showed full knee extension and 42 patients showed full knee flexion after surgery. The average HSS score showed no significant difference between experimental group (90.6 +/- 0.57 points) and control group (89.9 +/- 0.8 points) (t = 0.714, P > 0.05). The KT-1000 measurement (133N) was larger in control group (2.3 +/- 1.0 mm) than in experimental group (1.7 +/- 1.1 mm). There was significant difference in laxity between two groups (t = 6.427, P < 0.05). At 12 months post-operation, tunnel enlargement could be observed in both groups. The average enlargement of femoral tunnel was less in experimental group (17.3%) than control group (34.5%) (chi(2) = 4.17, P < 0.05). And the enlargement of tibial tunnel was less in experimental group (19.2%) than control group (36.2%) (chi(2) = 3.90, P < 0.05). CONCLUSIONS: The surgical technique using a periosteal flap wrapped with autologous hamstring tendons in ACL reconstruction has definite clinical efficacies. It can enhance the stability of knee and prevent the enlargement of bone tunnel. PMID- 20356555 TI - [Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients]. AB - OBJECTIVE: To investigate the appropriate dose of unfraction heparin and low molecular weight heparin (LMWH) in hemodialysis patients. METHODS: Thirty-eight hemodialysis patients were enrolled and randomly allocated into four groups.The initial bolus dose for the Low-dose (LH, n = 10) and high-dose heparin (HH, n = 10) groups were 35 U/kg and 55 U/kg, respectively.The repeated maintenance dose for both groups were 10 U/kg.h and 16 U/kg.h, respectively. Fragmin were administered as single bolus (60 U/kg or 80 U/kg) at 30 minutes before hemodialysis in Low-dose LMWH(LLMWH, n = 10) and High-dose LMWH (HLMW, n = 8) group, respectively. Furthermore, the dialysis circuits in LUFH and LLMWUFH groups were primed with with 4 mg/dl heparinized saline before hemodialysis. Glass bead active clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined using Sonoclot analysator at 0 h, 2 h and the end of hemodialysis at the arterial circuit and 2 h at the venous circuit. RESULTS: (1) LH and LUFH: the increase of gbACT and decrease of CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significant compared with baseline. While they recovered at the end of hemodialysis. No difference between the two groups at different time points was found, either. (2) LLMWH: No change were found in gbACT during hemodialysis. CR at the arterial circuit and the venous circuit were significantly decreased at 2 h and recovered at the end of hemodialysis. (3) LLMWUFH: gbACT at the arterial circuit was significantly increased only at 2 h of hemodialysis. CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significantly decreased and recovered when hemodialysis finished. (4) HH and HLMWH: gbACT were significantly increased and CR were rapidly decreased at both the arterial circuit and venous circuit at 2 h of hemodialysis. CONCLUSION: Low-dose heparin was effective and safe as anticoagulant in hemodialysis. Low-dose low-molecular-weight heparin was efficient in anticoagulation to some extent. However, High-dose low-molecular weight heparin, high-dose heparin and flushing with heparinized saline may increase the risk of hemorrhage. PMID- 20356556 TI - [Analysis of safety and effects on the oral whole cell/recombinant B subunit cholera vaccine in university students and workers]. AB - OBJECTIVE: To evaluate the safety, immunogenicity and protective efficiency of the oral whole cell/recombinant B subunit cholera vaccine in Beijing Olympic volunteers and workers. METHOD: Analyzing the incidence rate of adverse reaction and Protective Rate (PR) after taking the vaccine in Olympic volunteers in 6 universities in Beijing; comparing the anti-cholera toxin (CT) detected with ELISA prior and after taking the vaccine in Olympic workers. RESULTS: The total rate of adverse reaction of Olympic volunteers was 0.38%; the main side effects were gastrointestinal symptoms, such as bellyache and diarrhea which were mild and temple; the acute diarrhea incidence rate of Olympic volunteers after taking the vaccine was significantly lower than those not taking it, the PR was 76.27%; the positive rate of anti-CT of Olympic workers after taking the vaccine was significantly higher than those before taking it, the levels of anti-CT titers declined after 6 months since they had taken the vaccine. CONCLUSION: The results from above two observed population indicate that the oral rBS-WC cholera vaccine is efficient and safe. PMID- 20356557 TI - [Analysis of correlation factors for cervical intraepithelial neoplasia in married women in Beijing, China]. AB - OBJECTIVE: To investigate the characteristic of precancerous conditions of cervical intraepithelial neoplasia (CIN) and its related high-risk factors among the married women in Beijing, China. METHODS: Based upon the method of cross sectional survey, 6339 married women at reproductive age from 25 to 54 years old were selected randomly in a total of 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The interview was carried out with unified questionnaires and gynecological examinations. And the cervical Pap smear was used for liquid-based cytological examination and the cervical secretion for detection of high-risk human papillomavirus (HPV) DNA. Furthermore, the women with abnormal cervical cytology received colposcopy and cervical biopsy. RESULTS: (1) Among 6, 339 study subjects, 374 cases had CIN and the prevalence rate was 5.9%; (2) For the cases with cervical cytology positive results, cervical biopsy showed an elevated level of abnormal cytology and an increased incidence of cervical lesions; (3) The peak age of CIN prevalence was 30 to 34 years old and there was a high grade of cervical neoplasia; (4) Among the population, the infection rate of high-risk HPV was 9.9% and the infection rate of high-risk HPV in positive cytological group (41.2%) was significantly higher than that in negative cytological group (6.6%); (5) The infection rate and DNA load of high risk HPV increased following the severity grade of CIN. CONCLUSION: In Beijing, married women at 30 to 34 years old are the high-risk group in CIN incidence and the infection of high-risk HPV is an independent risk factor. Liquid-base cytology combined with high-risk HPV DNA test is a viable method to discover CIN in time and prevent the incidence of cervical cancer. PMID- 20356558 TI - [The effect of NaCl solution with different concentration on the resuscitation of hemorrhagic shock]. AB - OBJECTIVE: To observe the clinical results of different concentration NaCl solution in hemorrhagic shock resuscitation. METHODS: The 75 cases with hemorrhagic shock were divided into five groups by means of random number table. Treat the cases with 0.9% (control group), 3%, 4.5%, 6% and 7.5% NaCl solution, respectively. Observe the changes of BP, HR, blood gas, renal function, electrolyte concentration of plasma, before and after treatment. RESULTS: After transfusion, compared with groups of 0.9% NS, the mean BP of patients in other four groups rise more quickly but only the group of 4.5% can last 30 minutes (P < 0.05), and K(+) of plasma in groups of 6%, 7.5% NS decline more obviously (P < 0.05), the group of 4.5% maintain the best lever. CONCLUSION: The mean BP of patients rise quickly and continue for a long time, in the group of 4.5%. Meanwhile the internal environment of the body maintain relatively stable in the group of 4.5%. PMID- 20356559 TI - [Surgical treatment of bilateral thoracotomy in patients with lesions of left main bronchus invading carina]. AB - OBJECTIVE: To investigate the outcome for surgical treatment of bilateral thoracotomy in patients with lesions of left main bronchus invading carina by bilateral thoracotomy. METHODS: The clinical data of 4 patients with lesions of left main bronchus invading carina undergoing bilateral thoracotomy were retrospectively reviewed. RESULTS: There were two male and two female patients with a median age of 37.5 (range: 27 - 55) years old. Four patients were all accessed by bilateral thoracotomy, and received carinal reconstruction. Of these 4 patients, three patients received left pneumonectomy and one patient received carinal resection without concomitant pulmonary resection. Pathological results showed that one patient had tuberculosis. And other three patients were of 1 squamous cell carcinoma and 2 adenoid cystic carcinomas. Three patients received mechanical ventilation for a period of 3 - 21 days. one patient died of anastomotic dehiscence at 5 days postoperatively. CONCLUSION: Bilateral thoracotomy is an alternative approach for relatively young patients with decent cardiopulmonary functions with lesions of left main bronchus invading carina. Operation type should be based on histopathological type and length of involved left main bronchus. PMID- 20356560 TI - [Construction and clinical application of lentivirus-AQP4 expressing vector]. AB - OBJECTIVE: To construct the human aquaporin-4 (AQP4) expressing vector and detect anti-AQP4 antibody in serum of patients with neuromyelitis optica (NMO). METHODS: RNA was extracted from human glioblastoma and AQP4 cDNA obtained through RT PCR.The fragment was cloned into the lentiviral expressing vector (iDUET101) and transformed into competent strain Hb101 for later amplification; plasmids were extracted from the amplified positive-bacteria-colony, sequenced and transfected into HEK-293T cells. Expression of AQP4 was identified by RT-PCR, Western blot and immunofluorescence assay. And anti-AQP4 antibody in human serum was tested. RESULTS: The sequence of target fragment matched with that of human AQP4 fragment sequences (NM_001650) completely. The constructed AQP4 fragment transfected in HEK-293T cell was tested by immunofluorescent examination and it exhibited obvious fluorescence located in cell membrane. Western blot test was positive. And the fragment was about 34 KD. Cellular immunofluorescence examination showed 11 examples of 12 NMO patient serums (91.7%) were positive, 4 in 34 multiple sclerosis (11.8%) positive and negative in all 50 serum samples of healthy controls. CONCLUSION: The HEK-293T cell transfected with lentivirus-AQP4 vector can express stably. And the expressed fragment may be applied in clinical examination. PMID- 20356561 TI - The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation. AB - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of topotecan as second-line treatment for small cell lung cancer (SCLC). DATA SOURCES: Bibliographic databases were searched from 1990 to February 2009, including the Cochrane library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE In Process & Other Non-Indexed Citations. Bibliographies of related papers were assessed and experts were contacted to identify additional references and the manufacturer's submission to NICE was also searched. REVIEW METHODS: Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers using a standard form. For the clinical effectiveness review, the studies were randomised controlled trials (RCTs), which included adult participants with relapsed SCLC who responded to first-line treatment and for whom re-treatment with first-line therapy was inappropriate. The treatment was topotecan (oral or intravenous, i.v.) compared with one another, best supportive care (BSC) or other chemotherapy regimens. Outcomes included measures of response or disease progression and measures of survival. For the cost-effectiveness review studies were eligible for inclusion if they reported cost-effectiveness, cost-utility, cost-benefit or cost consequence analyses. Data extraction and quality assessment of included studies was undertaken by one reviewer and checked by a second. Studies were synthesised through a narrative review with full tabulation of results. An independent economic model estimated the cost-effectiveness of topotecan (oral or i.v.) compared with BSC. The model used survival analysis methods to derive estimates of mean survival for patients treated with topotecan or receiving BSC alone. These were combined with quality of life (QoL) weights to derive estimates of mean quality-adjusted life expectancy for patients receiving BSC alone or topotecan plus BSC. Categories of costs included in the model included drug use, chemotherapy administration and on-treatment monitoring, management of adverse events, monitoring for disease progression and palliative care. RESULTS: A total of 434 references were identified of which five were included in the clinical effectiveness review. In these trials topotecan was compared with BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin) and vincristine] or amrubicin, or oral topotecan was compared with i.v. topotecan. No economic evaluations were identified. There were no statistically significant differences between groups when i.v. topotecan was compared with either CAV or oral topotecan for overall response rate (ORR). Response rate was significantly better in participants receiving i.v. amrubicin than in those receiving a low dose of i.v. topotecan (38% versus 13%, respectively, p = 0.039). There was a statistically significant benefit in favour of oral topotecan compared with BSC (HR 0.61, 95% CI 0.43 to 0.87, p = 0.01). Drug acquisition costs for four cycles of treatment were estimated at 2550 pounds for oral topotecan and 5979 pounds for i.v. topotecan. Non-drug treatment costs accounted for an additional 1097 pounds for oral topotecan and 4289 pounds for i.v. topotecan. Total costs for the modelled time horizon of 5 years were 4854 pounds for BSC, 11,048 pounds for oral topotecan and between 16,914 pounds and 17,369 pounds for i.v. topotecan (depending on assumptions regarding time progression). Life expectancy was 0.4735, 0.7984 and 0.7784 years for BSC, oral topotecan and i.v. topotecan respectively. Total quality-adjusted life-years (QALYs) were 0.2247 and 0.4077, for BSC and oral topotecan respectively, resulting in an incremental cost-effectiveness ratio (ICER) of 33,851 pounds per QALY gained. Total QALYs for i.v. topotecan were between 0.3875 and 0.4157 (depending on assumptions regarding time progression) resulting in an ICER between 74,074 pounds and 65,507 pounds per QALY gained. CONCLUSIONS: Topotecan appeared to be better than BSC alone in terms of improved survival, and was as effective as CAV and less favourable than i.v. amrubicin in terms of response. Oral topotecan and i.v. topotecan were similar in efficacy. Topotecan offers additional benefit over BSC, but at increased cost. ICERs for i.v. topotecan, compared with BSC, were high and suggest that it is unlikely to be a cost-effective option. The ICER for oral topotecan is at the upper extreme of the range conventionally regarded as cost-effective from an NHS decision making perspective. Further research into the QoL of patients with relapsed SCLC could identify the impacts of disease progression and treatment response. PMID- 20356562 TI - Analysis of cholinesterases in human prostate and sperm: implications in cancer and fertility. AB - Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are postulated to play non-cholinergic roles in cellular physiology. The probable implication of cholinesterases (ChEs) in several human pathologies prompted us to study the cholinergic components in the male reproductive system. Surgical pieces of prostatic cancer (PC) and benign prostatic hyperplasia (BPH) were analyzed for AChE and BChE activity. Loosely (S1) and tightly (S2) bound AChE and BChE forms were characterized by sedimentation analysis. The mean AChE activity in BHP samples was 2.38+/-0.56 mU/mg (nmol of the substrate hydrolysed per minute and per milligram protein) and 2.57+/-0.61 mU/mg in S1 and S2, respectively. The AChE activity did not vary with cancer, showing 2.46+/-0.45 mU/mg in S1 and 2.70+/ 0.53 mU/mg in S2 from PC samples. Amphiphilic dimers and monomers and hydrophilic dimers of AChE were identified in BHP and PC tissues. Their contribution was affected by cancer with a great increase in hydrophilic dimers in the cancerous samples. Significant levels of both AChE and BChE activities were found in seminal fluid and homogenates from spermatozoids. Enzymatic activity dropped in samples with abnormal seminal parameters as sperm count and mobility. PMID- 20356563 TI - Structural binding evidence of the trypanocidal drugs berenil and pentacarinate active principles to a serine protease model. AB - Bovine trypsin is a model system for the serine protease class of enzymes, which is an important target for contemporary medicinal chemistry. Some structural and thermodynamic reports are available on its interaction with benzamidine-based compounds but no structural information is available so far on its binding modes to the active principles of the trypanocidal drugs Pentacarinate (pentamidine) and Berenil (diminazene). The crystallographic structures of bovine beta-trypsin in complex with the ligands were determined to a resolution of 1.57 A (diminazene) and 1.70 A (diminazene and pentamidine). The second benzamidine moieties in these inhibitors are bound to the enzyme in different hot spots and only few hydrogen bonds mediate these interactions. Thermodynamic parameters for the association of pentamidine with beta-trypsin reveal that this inhibitor has about 1.3-fold lower affinity than diminazene. Moreover its binding mode resembles other benzamidine-based compounds that assess the aryl binding pocket of the enzyme; however, with almost 2.5-fold higher affinity. This is the first structural evidence of the binding of Berenil and Pentacarinate active principles trypanocidal drugs to serine proteases. PMID- 20356565 TI - Heterologous expression of fused genes encoding the glycoprotein 5 from PRRSV: a way for producing functional protein in prokaryotic microorganism. AB - Based on the bioinformatics analysis of the gene encoding glycoprotein 5 (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) isolate HH08, two gene fragments were amplified by polymerase chain reaction (PCR), deleting the signal peptide and transmembrane sequences in GP5 gene. Both gene fragments were designated GP5a and GP5b, respectively. They were ligated with a linker and cloned into prokaryotic expression vector, pET-30a. Expression of the protein of interest was induced by isopropyl beta-d-1-thiogalactopyranoside. The purified protein was used as an immunogen to elicit antibody in rabbit. The immunoreactivity of the protein was determined using ELISA and Western blot. Biologically active GP5 and anti-GP5 antibody inhibited cell infection by PRRSV. Moreover, the antibody produced in this study was capable of detecting the cell infection by PRRSV and distinguishing this virus from other viruses. PMID- 20356564 TI - Conditional cell-wall mutants of Saccharomyces cerevisiae as delivery vehicles for therapeutic agents in vivo to the GI tract. AB - Strains of Saccharomyces cerevisiae capable of lysis upon conditional down regulation of cell-wall biogenesis genes (SRB1 and PKC1) have been reported. Here, we show that they lyse and release recombinant protein not only under laboratory conditions, but (more importantly) under conditions found in the human stomach and duodenum. These findings provide proof that, in principle, such conditional lysis strains could be used as an integral part of a system for the oral delivery of therapeutic proteins. However, the current mechanism of conditional lysis is based on the use of the MET3 promoter which requires addition of methionine and cysteine for down-regulation of SRB1 and PKC1. This requirement makes it difficult to apply in vivo. We reasoned that promoters, suitable for in vivo down-regulation of lysis-inducing genes, could be identified amongst yeast genes whose transcript abundance is reduced under conditions found in the human gut. A microarray experiment identified a number of candidate genes with significantly reduced transcript levels under simulated human gut conditions. The greatest effects were seen with ANB1, TIR1, and MF(ALPHA)2), and we propose that their promoters have the potential to be used in vivo to achieve yeast lysis in the gut. PMID- 20356566 TI - Anti-amyloidogenic property of leaf aqueous extract of Caesalpinia crista. AB - Amyloid beta (Abeta) is the major etiological factor implicated in Alzheimer's disease (AD). Abeta(42) self-assembles to form oligomers and fibrils via multiple aggregation process. The recent studies aimed to decrease Abeta levels or prevention of Abeta aggregation which are the major targets for therapeutic intervention. Natural products as alternatives for AD drug discovery are a current trend. We evidenced that Caesalpinia crista leaf aqueous extract has anti amyloidogenic potential. The studies on pharmacological properties of C. crista are very limited. Our study focused on ability of C. crista leaf aqueous extract on the prevention of (i) the formation of oligomers and aggregates from monomers (Phase I: Abeta(42)+extract co-incubation); (ii) the formation of fibrils from oligomers (Phase II: extract added after oligomers formation); and (iii) dis aggregation of pre-formed fibrils (Phase III: aqueous extract added to matured fibrils and incubated for 9 days). The aggregation kinetics was monitored using thioflavin-T assay and transmission electron microscopy (TEM). The results showed that C. crista aqueous extract could able to inhibit the Abeta(42) aggregation from monomers and oligomers and also able to dis-aggregate the pre-formed fibrils. The study provides an insight on finding new natural products for AD therapeutics. PMID- 20356568 TI - [Anterior ethmoidal artery at ethmoidal labyrinth: Bibliographical review of anatomical variants and references for endoscopic surgery]. AB - INTRODUCTION: The anterior ethmoidal artery (AEA) has a trajectory with multiple anatomical variations. In addition, there are no clear references to locate it, so it is easy to produce an iatrogenic lesion. The goal of this study was to carry out a bibliographical review to analyse variants and endoscopic reference reports in the scientific literature. MATERIAL AND METHODS: A review in Medline and Embase data bases was carried out, looking for AEA-related anatomical and radiological studies. After the revision, the principal study results, together with several distances and angles useful for locating the AEA, are presented in this study. RESULTS: There were 13 main articles that analysed a total of 1388 AEA. It was absent from 2 to 14%. It was identifiable in computed tomography (CT) between 95 and 100%. It was located between the second and third ethmoidal lamella in 74.2% and at the skull base level in 66.6%. Ethmoidal sinuses pneumatisation was related to AEA location at the skull base. Between 83 and 85.3%, it was found at the suprabullar recess. CONCLUSIONS: CT is useful for presurgery planning. AEA are more frequent between the second and third lamella and at skull level. Ethmoidal pneumatisation and Keros grades could be predictive factors for AEA relationship with the skull base level. The AEA, the axilla of the middle turbinate and the superomedial edge of the nose are in a straight line, being a simple and useful reference in endoscopic sinus surgery. PMID- 20356567 TI - Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination. AB - Hepatitis B-specific memory B cell (HSMBC) frequencies were measured following hepatitis B vaccination in 15 HIV uninfected and 12 HIV infected adolescents. HSMBC were detected at significantly lower frequencies in HIV infected than in HIV uninfected individuals. The detection of HBsAb >10mIU/ml at study week 28 was strongly associated with the detection of HSMBC and a direct correlation between HBsAb titers and HSMBC frequencies was observed. In HIV uninfected individuals, antibody titers >1000mIU/ml were associated with higher HSMC frequencies. Lower HSMBC frequencies, reduced memory B cell (MBC) proliferation, and altered B cell phenotypes were measured in viremic HIV infected individuals compared with aviremic HIV infected or HIV uninfected individuals. PMID- 20356569 TI - Observing or producing a motor action improves later perception of biological motion: evidence for a gender effect. AB - Two experiments are presented addressing the issue of whether observing (visual priming) or producing (motor priming) a running activity during a very short period (30s) facilitates the perception of the direction of a point-light runner embedded in a dense dynamical mask. Experiment 1 showed that perceptual judgements improved and response time increased in the visual priming compared to the neutral priming condition (video of a moving car) in which judgements were at random. Because this effect was observed for male participants only, we performed a second experiment with the aim of evaluating the role of gender congruency in the visual priming condition. Results confirmed the facilitation effect and demonstrated that this effect was strictly dependent on the gender congruency between the perceiver and the priming information. Moreover, we found that actually producing a motor activity similar to the one presented in the video sequence improved to the same extent participants' judgement of the direction of the point-light runner, without any gender effect. As a whole, these findings argue in favour of common representation for the perception and the production of human movement and showed that the perception of biological motion can be improved by prior motor activity either performed or observed. However, the gender-dependent effect of visual priming suggested that motor repertoire differed in males and females. PMID- 20356571 TI - [Interest of tricuspid annular displacement (TAD) in evaluation of right ventricular ejection fraction]. AB - INTRODUCTION: The ultrasound assessment of RV structure and function is often sub optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles. METHODS: We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF<40%). RESULTS: The MRI RVEF was positively correlated with TAD (R(2)=0,65; p<0,0001). A value of TAD <14mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9+/-1.64mm; range: 13.3 to 24.8mm). Negative correlation was found between TAD and age (R(2)=0,36; p<0,0001). CONCLUSION: Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment. PMID- 20356570 TI - Docosahexaenoic acid confers neuroprotection in a rat model of perinatal hypoxia ischemia potentiated by Escherichia coli lipopolysaccharide-induced systemic inflammation. AB - OBJECTIVE: Lipopolysaccharide pretreatment potentiates hypoxic ischemic injury. We hypothesized that docosahexaenoic acid pretreatment would improve function and reduce brain volume loss in this rat model of perinatal brain injury and inflammation. STUDY DESIGN: Seven-day-old rats were divided into 3 groups: intraperitoneal docosahexaenoic acid 1 mg/kg and lipopolysaccharide 0.1 mg/kg, 25% albumin and lipopolysaccharide, and normal saline. Injections were given 2.5 hours before carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor function testing and brain volume loss assessment on postnatal day 14. RESULTS: Docosahexaenoic acid pretreatment improved vibrissae forepaw placing scores compared with albumin/lipopolysaccharide (mean+/-standard deviation weighted score/20: 17.72+/-0.92 docosahexaenoic acid/lipopolysaccharide vs 13.83+/-0.82 albumin/lipopolysaccharide; P<.007). Albumin/lipopolysaccharide rats scores were worse than those of the normal saline/normal saline rats (13.83+/ 0.82 vs 17.21+/-0.71; P=.076). No significant differences in brain volume loss were observed among groups. CONCLUSION: Lipopolysaccharide inflammatory stimulation in conjunction with hypoxic ischemic resulted in poorer function than hypoxic ischemic alone. Docosahexaenoic acid pretreatment had significantly improved function in neonatal rats exposed to lipopolysaccharide and hypoxic ischemic. PMID- 20356572 TI - Exposure to a novel context after extinction causes a renewal of extinguished conditioned responses: implications for the treatment of fear. AB - Renewal gives an experimental model for the relapse of fear symptoms following exposure therapy. While renewal of extinguished fear in humans has been observed following a return to the original context in which fear was acquired (ABA design), it has been more difficult to show upon presentation of a novel context (ABC design). The present experiment used a particularly strong context manipulation in a fear conditioning procedure. Context was manipulated by using large photographs of real environments taken from various angles and was present throughout the entire experiment. A renewal of cognitive expectancy was found in both ABA and ABC renewal designs, although it was larger in the former than in the latter. Response times in making the expectancy judgments increased when there was a change to a new context. The results demonstrate consistency in fear renewal effects between human and animal studies and suggest that relapse following exposure therapy via renewal remains a danger when people encounter a previously feared object in a novel context. PMID- 20356573 TI - Fcgamma receptors exhibit different phagocytosis potential in human neutrophils. AB - In neutrophils, two receptors for IgG antibodies, namely FcgammaRIIA and FcgammaRIIIB are constitutively expressed, and a third one, FcgammaRI, can be upregulated by interferon-gamma. Whether FcgammaRIIIB is capable of triggering phagocytosis by itself is still controversial. The main role of FcgammaRI has not been clearly established in these cells. To address this problem, neutrophils were treated with interferon-gamma, and then phagocytosis mediated by each type of Fcgamma receptor was evaluated by flow cytometry. FcgammaRIIA was the most efficient receptor for phagocytosis. FcgammaRIIIB could mediate phagocytosis but much less efficiently than FcgammaRIIA. Both FcgammaRIIA- and FcgammaRIIIB mediated phagocytosis were blocked by inhibitors of Src family kinases, Syk, PI 3 K, and ERK. In contrast, interferon-gamma-induced FcgammaRI was not able to mediate phagocytosis. Also, FcgammaRI did not activate ERK in the nucleus, but was however able to stimulate an efficient calcium rise. These data show that different neutrophil Fcgamma receptors possess different phagocytosis capabilities: FcgammaRIIA and FcgammaRIIIB, but not FcgammaRI, promote phagocytosis. PMID- 20356574 TI - The Earth is flat when personally significant experiences with the sphericity of the Earth are absent. AB - Participants with personal and without personal experiences with the Earth as a sphere estimated large-scale distances between six cities located on different continents. Cognitive distances were submitted to a specific multidimensional scaling algorithm in the 3D Euclidean space with the constraint that all cities had to lie on the same sphere. A simulation was run that calculated respective 3D configurations of the city positions for a wide range of radii of the proposed sphere. People who had personally experienced the Earth as a sphere, at least once in their lifetime, showed a clear optimal solution of the multidimensional scaling (MDS) routine with a mean radius deviating only 8% from the actual radius of the Earth. In contrast, the calculated configurations for people without any personal experience with the Earth as a sphere were compatible with a cognitive concept of a flat Earth. PMID- 20356575 TI - Speech-and-gesture integration in high functioning autism. AB - This study examined iconic gesture comprehension in autism, with the goal of assessing whether cross-modal processing difficulties impede speech-and-gesture integration. Participants were 19 adolescents with high functioning autism (HFA) and 20 typical controls matched on age, gender, verbal IQ, and socio-economic status (SES). Gesture comprehension was assessed via quantitative analyses of visual fixations during a video-based task, using the visual world paradigm. Participants' eye movements were recorded while they watched videos of a person describing one of four shapes shown on a computer screen, using speech-and gesture or speech-only descriptions. Participants clicked on the shape that the speaker described. Since gesture naturally precedes speech, earlier visual fixations to the target shape during speech-and-gesture compared to speech-only trials, would suggest immediate integration of auditory and visual information. Analyses of eye movements supported this pattern in control participants but not in individuals with autism: iconic gestures facilitated comprehension in typical individuals, while it hindered comprehension in those with autism. Cross-modal processing difficulties in autism were not accounted for by impaired unimodal speech or gesture processing. The results have important implications for the treatment of children and adults with this disorder. PMID- 20356576 TI - When do we simulate non-human agents? Dissociating communicative and non communicative actions. AB - There is strong evidence that we automatically simulate observed behavior in our motor system. Previous research suggests that this simulation process depends on whether we observe a human or a non-human agent. Measuring a motor priming effect, this study investigated the question of whether agent-sensitivity of motor simulation depends on the specific action observed. Participants saw pictures depicting end positions of different actions on a screen. All postures featured either a human or non-human agent. Participants had to produce the matching action with their left or right hand depending on the hand presented on the screen. Three different actions were displayed: a communicative action (emblem), a transitive (goal-directed) action and an intransitive action. We found motor priming effects of similar size for human and non-human agents for transitive and intransitive actions. However, the motor priming effect for communicative actions was present for the human agent, but absent for the non human agent. These findings suggest that biological tuning of motor simulation is highly action-selective and depends on whether the observed behavior appears to be driven by a reasonable goal. PMID- 20356577 TI - [Comorbidity in acute or chronic decompensated heart failure. Are they grayhounds or bloodhounds?]. PMID- 20356578 TI - [The adult age in the medical field]. AB - Two erroneous concepts have been developed over the last two decades In the Spanish medical literature and clinical practice: a) "mature minor," supposed subject whose rights prevail over those of his/her parents and b) "legal age for health care-related decisions" (16 years), really non-existent in our legal regulations. Several thoughts are given concerning the legislations that have been offered with respect to the "legal-age for health care-related decisions". PMID- 20356579 TI - Clinically significant and sustained weight loss is achievable in obese women with polycystic ovary syndrome followed in a regular medical practice. AB - OBJECTIVE: To determine the proportion of obese women with polycystic ovary syndrome (PCOS) losing clinically significant amounts of weight during a standard follow-up by an endocrinologist. DESIGN: Retrospective cohort study. SETTING: Reproductive Endocrinology Clinic of an academic center. PATIENT(S): Obese patients with PCOS assessed between May 2002 and September 2008. INTERVENTION(S): General nonstandardized advice on weight loss and exercise. MAIN OUTCOME MEASURE(S): Proportion of women losing >=5% or >=10% of their initial weight at each of the following time interval: 2-6 months, 6-12 months, 12-18 months, 18-24 months, 24-36 months, and beyond 36 months. RESULT(S): One hundred seventeen patients with PCOS and with a mean body mass index (BMI) of 38.7 kg/m(2) and mean age of 28.5 years were followed-up for a median duration of 21.9 months (range, 2.0-61.8 months), with a median of two visits per year. More than 40% of these women lost >=5% of their initial weight after >6 months of follow-up, and >=20% lost >=10% after 1 year of follow-up. More important, these proportions were maintained up to >=3 years. CONCLUSION(S): It is possible for obese women with PCOS to achieve clinically significant and sustained weight loss by following simple advices given in a regular clinical care setting. Therefore, practitioners should not underestimate their impact to facilitate weight loss in women with PCOS. PMID- 20356581 TI - Congenital malformations of the female genital tract: the need for a new classification system. AB - Current proposals for classifying female genital anomalies seem to be associated with limitations in effective categorization, creating the need for a new classification system that is as simple as possible, clear and accurate in its definitions, comprehensive, and correlated with patients' clinical presentation, prognosis, and treatment on an evidence-based foundation. Although creating a new classification system is not an easy task, it is feasible when taking into account the experience gained from applying the existing classification systems, mainly that of the American Fertility Society. PMID- 20356582 TI - Does estrogen directly modulate anti-mullerian hormone secretion in women? AB - OBJECTIVE: To investigate whether estrogen may modulate anti-mullerian hormone (AMH) expression in women. DESIGN: Prospective analysis. SETTING: Fertility clinic of tertiary university hospital. PATIENT(S): Cycling infertile women. INTERVENTION(S): Blood samples were taken at the early, middle, and late follicular phase in five groups: spontaneous cycle (n=10), ovulation induction with clomiphene-citrate (n=15) or gonadotropins (n=9), controlled ovarian hyperstimulation for IVF (COH-IVF; n=10) and in women who were treated with exogenous E2 for frozen-thawed embryo-transfer (FET) with no follicular development (n=20). MAIN OUTCOME MEASURE(S): AMH and E2 serum levels. RESULT(S): Basal serum AMH and E2 levels were similar in all groups. AMH levels were stable in all women during the follicular phase except for significant reduction in the COH-IVF group. In women in the FET group with high E2 levels, comparable to the COH-IVF group, AMH levels remained stable. CONCLUSION(S): In women, estrogen does not appear to have a direct role in AMH regulation. PMID- 20356583 TI - Diagnosis of endometriosis of the rectovaginal septum using introital three dimensional ultrasonography. AB - OBJECTIVE: To evaluate the diagnostic accuracy of introital three-dimensional (3D) transvaginal sonography for preoperative detection of rectovaginal septal endometriosis. DESIGN: Ultrasonographic results were compared with surgical and histologic findings. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): This prospective study included 39 women with suspected rectovaginal endometriosis. INTERVENTION(S): All patients underwent 3D transvaginal sonography for the evaluation of the rectovaginal septum, before undergoing laparoscopic radical resection of endometriosis. Rectovaginal endometriosis was defined as hypoechoic areas, nodules, or anatomic distortion of this specific location. MAIN OUTCOME MEASURE(S): Sensitivity, specificity, and likelihood ratios (positive or negative) were calculated with 95% confidence intervals (CIs). RESULT(S): Surgery associated with histopathologic evaluation revealed deep endometriosis in the rectovaginal septum in 19 patients. The specificity, sensitivity, positive likelihood ratio, and negative likelihood ratio were 94.7% (95% CI, 78.6%-99.7%), 89.5% (95% CI, 73.3%-94.5%), 17.2 (95% CI, 2.51-115), and 0.11 (95% CI, 0.03 0.41), respectively. CONCLUSION(S): Introital 3D ultrasonography seems to be an effective method for the diagnosis of endometriosis of the rectovaginal septum and should be included in the preoperative evaluation of patients with clinical suspicion of deep endometriosis. PMID- 20356584 TI - Letrozole monotherapy in the treatment of uterine myomas. PMID- 20356585 TI - Will decreasing assisted reproduction technology costs improve utilization and outcomes among minority women? AB - OBJECTIVE: To evaluate assisted reproduction technology (ART) usage and outcomes in minority women seeking care at enhanced access, military ART programs. DESIGN: Retrospective cohort. SETTING: Federal ART programs. PATIENT(S): Two thousand fifty women undergoing first cycle, fresh, nondonor ART from 2000 to 2005. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rate of ART use, clinical pregnancy rate, live birth rate. RESULT(S): African American women had an almost fourfold increased use of ART and Hispanic women had decreased use. Clinical pregnancy rates were significantly lower for African American women compared with white women (46.1% vs. 52.6%, relative risk [RR] 0.88; 95% confidence interval [CI], 0.78-0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74; 95% CI, 0.63-0.91). CONCLUSION(S): Economics appear to influence ART use by African American women but not Hispanic women. Despite increased use by African American women, outcomes in this group were worse when compared with Caucasian women. Improving access through decreased cost may increase use by some but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups. PMID- 20356587 TI - Metformin, naltrexone, or the combination of prednisolone and antiandrogenic oral contraceptives as first-line therapy in hyperinsulinemic women with polycystic ovary syndrome. AB - To compare the short-term effects of metformin (M), naltrexone (N), and a combination of OC and prednisolone (OC/Pr) on the metabolic state and the ovarian function of PCOS women, we randomized 29 women to a 3-month course of therapy. We observed significant improvements in hyperandrogenemia and ovulation rates in PCOS women of all three groups, in the absence of changes in the metabolic state, suggesting that insulin resistance in PCOS patients is only one of several factors leading to hyperandrogenemic ovarian failure. PMID- 20356588 TI - Surgical treatment of endometriosis: a prospective randomized double-blinded trial comparing excision and ablation. AB - OBJECTIVE: To compare reduction of pain following laparoscopy after ablation or excision of endometriosis. DESIGN: A prospective, randomized, double-blind study. SETTING: Endometriosis and pelvic pain clinic at a university teaching hospital. PATIENT(S): Women of reproductive age presenting with pelvic pain and visually proved endometriosis. INTERVENTION(S): Subjects completed a questionnaire rating their various pains using visual analogue scales (VASs). After visual identification subjects were assigned randomly to treatment with ablation or excision by supervised training gynecologists as primary surgeon. Follow-up questionnaires at 3, 6, 9, and 12 months documented pain levels. MAIN OUTCOME MEASURE(S): Change in overall pain VAS score at 12 months after operation. RESULT(S): There was no significant difference in reduction in overall pain VAS scores at 12 months when comparing ablation and excision. CONCLUSION(S): This study has not been able to demonstrate a significant difference in pain reduction between ablation and excisional treatments. Nonsignificant trends suggest that a larger study may find a difference in outcomes looking at dyspareunia or dyschezia. PMID- 20356589 TI - Hyaluronic acid reagent suppressed endometriotic lesion formation in a mouse model. AB - In an animal endometriosis model, the administration of hyaluronic acid (HA) reagent significantly suppressed the formation of endometriotic lesions in both number and weight. This effect was found when HA treatment was conducted at the time of endometrial fragment inoculation. PMID- 20356590 TI - Is "restoration of ovarian function or ovarian reserve" possible after ovarian surgery? PMID- 20356591 TI - Free-hand versus novel specialised jig guidance for the passing of intramedullary wires in olecranon fracture fixation: a comparative study. AB - The treatment of olecranon fractures frequently involves the use of tension-band fixation. Although associated with high union rates, this method has a high incidence of morbidity associated with soft tissue compromise and limitation of range of movement requiring frequent re-operation for removal of metal. We describe the use of a simple jig to ensure intramedullary placement of longitudinal K-wires and compare the accuracy of placement of Kirschner (K)-wires using this device with the traditional free-hand method. We found the distance from the centre of the medullary canal, the range and standard deviations of K wire positions to be significantly more precise when the jig was used. This has applications for the use of the device, both with standard metallic radio-opaque wires and potentially with bio-absorbable pins. PMID- 20356593 TI - Promoting female reproductive and sexual health: the importance of attitude. PMID- 20356594 TI - Insulin resistance is associated with increased cholesterol synthesis, decreased cholesterol absorption and enhanced lipid response to statin therapy. AB - OBJECTIVE: Increasing insulin resistance is associated with a shift in cholesterol metabolism to increased synthesis and decreased absorption. Since statins inhibit cholesterol synthesis, we hypothesized that insulin-resistant patients will have greater LDL cholesterol (LDL-C) response to statins than insulin-sensitive patients. METHODS: High-risk vascular patients not on lipid lowering therapy were recruited and treated with Atorvastatin 80 mg for 6 weeks. Percent LDL-C response to Atorvastatin was related to insulin sensitivity using the quantitative insulin sensitivity check index (QUICKI). Comparisons: (1) correlation between %LDL-C response and QUICKI. (2) Differences in cholesterol metabolism markers in insulin-resistant (lowest tertile QUICKI) vs insulin sensitive patients (highest tertile of QUICKI). (3) Correlation of QUICKI with percent LDL-C response after correction for cholesterol metabolism markers. RESULTS: 154 patients were enrolled of which 66 were suitable for this sub-study. Average LDL-C reduction was 57+/-12% (mean+/-SD). QUICKI correlated negatively with percent LDL-C reduction (Pearson's r=-0.258, p=0.037) and on regression analysis explained approximately 7% (R2=0.067) of the variation in percent LDL-C response which approximates that reported by pharmacogenomics. Insulin-resistant patients had higher levels of cholesterol synthesis markers (desmosterol, lathosterol) and lower levels of absorption markers (cholestanol, sitosterol) and the correlation between QUICKI and percent LDL-C response ceased to be significant when these factors were controlled for. CONCLUSIONS: Insulin resistant patients have superior LDL-C responses to statin therapy and that this may be related to increased cholesterol synthesis. BACKGROUND: Patients with features of the metabolic syndrome, e.g. high triglycerides (TG) and low high density lipoprotein cholesterol (HDL-C) may have an enhanced benefit from statin therapy. A retrospective analysis from the 4S investigators where the study population was stratified by HDL-C and TG quartiles revealed variations in statin efficacy. Patients who fell into both the lowest quartile of HDL-C (<39 mg/dl) and highest quartile of TG (>159 mg/dl) had a greater frequency of features of the metabolic syndrome (high BMI, hypertension, diabetes) than the patients in the highest quartile of HDL-C (>52 mg/dl) and lowest quartile of TG (<98 mg/dl). The 4S investigators suggested that patients with low HDL-C and high TG achieved an enhanced clinical benefit from statins compared to patients with high HDL-C and low TG with hazard ratios of 0.48 and 0.86 respectively and a treatment-by subgroup interaction p value of 0.03 [1]. Since the clinical benefit of statin therapy is directly proportional to achieved percent reduction in low density lipoprotein cholesterol (LDL-C) [2], we hypothesized that insulin-resistant patients would have greater percent decreases in LDL-C with statin therapy. PMID- 20356595 TI - All-cause and cardiovascular mortality in treated patients with severe hypertriglyceridaemia: A long-term prospective registry study. AB - OBJECTIVE: To examine all-cause and cardiovascular mortality in patients with severe hypertriglyceridaemia. METHODS: 337 patients aged less than 80 years (47 with diabetes, 75 women) with a fasting triglyceride concentration on at least two occasions of >5.0mmol/l were registered by 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2008 for 4353 person-years. The standardised mortality ratio (SMR) was calculated by comparison with the general population. RESULTS: The mean untreated total cholesterol concentration was 9.8 (SD 3.6)mmol/l for men and 11.9 (7.2)mmol/l for women and the corresponding geometric mean triglyceride concentration was 12.6 (inter-quartile range 7.3, 21.6) and 15.7 (8.2, 29.2)mmol/l. There were 70 deaths, including 35 from CHD and 7 from stroke. The SMR for CHD was raised at 327 (95% confidence intervals 228, 455; p<0.0001) and remained elevated after excluding patients with diabetes at registration (SMR=287, 95% CI 190, 419; p<0.0001), and after excluding patients with CHD at registration (SMR=259, 95% CI 158, 400; p=0.0003). The increased SMR was most marked in younger men aged 40-59 years (SMR=544, 95% CI 304, 897; p<0.0001). The SMR for stroke for patients aged 20-79 years was raised at 262 (95% CI 105, 540; p=0.04), as was all-cause mortality at 164 (95% CI 129, 208; p<0.001). CONCLUSION: Severe hypertriglyceridaemia is associated with a substantially increased mortality from cardiovascular disease, even in the absence of diabetes. In addition to lowering triglyceride concentrations to reduce the risk of pancreatitis, treatment should aim to reduce the overall cardiovascular risk. PMID- 20356596 TI - Chromatographic characterisation of ordered mesoporous silicas. Part II: Acceptor donor properties. AB - The ordered mesoporous siliceous materials: MCM41C16, MCM41C16-SH and MCM41C16 NH(2) (known as MCMs) having different surface functionalities were studied by inverse gas chromatography to characterise their acceptor-donor properties. The DN values denoting the donor number in the Gutmann scale and the AN* values denoting the acceptor number in the Riddle-Fowkes scale have been chosen in the estimation of the electron-acceptor parameter K(A) and electron-donor parameter K(D) values. The number and kind of the employed adsorbates have an influence on the results obtained. The problem of the number of adsorbates employed has been considered in the light of both results obtained in the present study and the data available in the literature for siliceous adsorbents with randomly ordered structures. Complementary information was obtained by X-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. PMID- 20356597 TI - Chromatographic characterisation of ordered mesoporous silicas: part I. Surface free energy of adsorption. AB - The ordered mesoporous siliceous materials: MCM41C16, MCM41C16-SH and MCM41C16 NH(2) (known as MCMs) having different surface functionalities were studied by inverse gas chromatography at infinite dilution of chromatographed substances to elucidate their adsorption and adhesive properties. The free energies of adsorption, DeltaG(ads), were calculated in two ways on the basis of the primary chromatographic data. The van der Waals component of the surface free energy, gamma(S)(vdW), was calculated by employing the Dorris-Gray method and the Schultz method. The van der Waals, gamma(S)(vdW), and specific, I(SP), components of the surface free energy were temperature dependent, and were expressed as the linear dependences. The suggested approach was also employed for non-ordered silica adsorbents on the basis of various literature data. PMID- 20356598 TI - Streamlined, two-column, simulated countercurrent chromatography for binary separation. AB - We report on a numerical and experimental study of two-column versions of streamlined, multicolumn, semi-continuous chromatography for binary separation. The systems combine a flexible node design, cyclic flow-rate modulation, and relayed operation of the inlet/outlet ports to extend the mass-transfer zone over the largest possible length, while keeping it inside the system at all times. One advantage of these streamlined designs is the simplicity of their physical realization: regardless of the number of columns, they only require two pumps to supply feed and desorbent into the system, while the flow rates of liquid withdrawn from the system are controlled by material balance using simple two-way valves. In one case, an extra pump is needed to recirculate the fluid in closed loop. A rigorous model-based optimization approach is employed in the optimal design of the cycles to generate solutions that are physically realizable in the experimental set-ups. The optimized schemes for two-column operation supply fresh feed into the middle of the system where the composition of the circulating fluid is closest to that of the feedstock fluid, and recover the purified products, extract and raffinate, alternately at the downstream end of the unit, while desorbent is continuously supplied into the upstream end of the system. By internally recycling part of the non-pure cut fraction, the scheme with a step of closed-loop recycling significantly reduces its solvent consumption. The feasibility and effectiveness of the reported two-column processes have been verified experimentally on the linear separation of nucleosides by reversed phase subject to 99% purity constraints on both products. It is shown that our processes compare favorably against single-column batch chromatography, steady state recycling, and four-column, open-loop SMB, for the same amount of adsorbent; they are also better than the four-column, closed-loop SMB at high feed throughputs. PMID- 20356599 TI - Major lipid classes separation of buttermilk, and cows, goats and ewes milk by high performance liquid chromatography with an evaporative light scattering detector focused on the phospholipid fraction. AB - An improved HPLC-ELSD method has been developed for the analysis of the lipid classes of buttermilk and milk from different species, focused in the phospholipids fraction without a prior fractionation step and in a single run. The total lipid profile analysis showed the major and minor lipid compounds as cholesterol esters, triacylglycerides, cholesterol, diacylglycerides, free fatty acids, monoacylglycerides, and also the polar compounds as glucosylceramide, lactosylceramide, phosphatidyl-ethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, sphingomyelin and lysophosphatidylcholine. The identification and quantification of the different compounds, using calibration curves made with individual standards and the low coefficients of variation obtained in the inter- and intra-assays showed the suitability of the developed method. In this study, we optimized and validated a quantitative HPLC-ELSD method at a concentration level suitable for routine analysis of the major lipid classes in milk and dairy products. PMID- 20356601 TI - CdTe nanocrystal-polymer composite thin film without fluorescence resonance energy transfer by using polymer nanospheres as nanocrystal carriers. AB - A series of positively charged polystyrene (PS) nanosphere emulsions were prepared by copolymerization of quaternary ammonium chloride cationic monomer with styrene via emulsifier-free emulsion polymerization. The average diameter of the nanospheres was tuned in the range of 35-100 nm by adjusting the recipe. The PS nanospheres were used as carriers of aqueous CdTe nanocrystals (NCs) by adsorbing them on the surface through static interaction. After attached to the nanospheres, NCs' stability against pH change and UV light irradiation was enhanced. The CdTe-PS composite nanospheres were blended with compatible poly (vinyl alcohol) (PVA) matrix to prepare fluorescent thin film by spin coating. CdTe-PS nanospheres had homogenous distribution in the thin film and their light scattering performance was largely reduced after solvent evaporated, as a result, the composite thin film was highly transparent. In the meantime, the immobilization effect of PS nanospheres prevented NCs from aggregation, thus they preserved original high fluorescence without fluorescence resonance energy transfer. The CdTe-PS/PVA composite solution has potential applications in light emitting devices by inkjet printing. PMID- 20356600 TI - Increasing selectivity in comprehensive three-dimensional gas chromatography via an ionic liquid stationary phase column in one dimension. AB - Recent advances in improving the selectivity and performance for a comprehensive, three-dimensional (3D) gas chromatograph (GC(3)) instrument are described. With GC(3), two six-port diaphragm valves are utilized as the interfaces between three, in-series capillary columns housed in a standard GC instrument fitted with a high data acquisition rate flame ionization detector (FID). Modulation periods for sampling from one column to the next are set so that sufficient slices (i.e., modulations) are acquired by the subsequent dimension resulting in comprehensive data. We present GC(3) instrumentation with significantly higher 3D peak capacity than previously reported. An average peak capacity production (i.e., per time) of 180 resolved peaks per minute was experimentally achieved for three representative analytes in a 3D diesel sample separation. This peak capacity production is about 4 times higher than our previous report. We also demonstrate the significant benefit of the added chemical selectivity of the three column GC(3) instrument relative to a two column GC x GC instrument, in which one of the three columns is a triflate ionic liquid stationary phase column with a high selectivity for phosphonated compounds (i.e., di-methyl-methyl phosphonate, di ethyl-methyl phosphonate and di-isopropyl-methyl phosphonate). Using all three separation dimensions, the 2D separation fingerprint of a diesel sample is simultaneously obtained along with selective information regarding the phosphonated compounds in the diesel samples in the additional dimension. PMID- 20356602 TI - Visible-light hydrogen generation using as photocatalysts layered titanates incorporating in the intergallery space ruthenium tris(bipyridyl) and methyl viologen. AB - A series of layered titanates containing in the interlayer space tris(2,2' bipyridyl)ruthenium(II) [Ru(bpy)(3)(2+)] or methyl viologen (MV(2+)) or both has been prepared and characterized by elemental analyses, XRD, and optical and vibrational spectroscopy. Incorporation of Ru(bpy)(3)(2+) and MV(2+) is confirmed by the increase of the distance between the titanate layers. The presence of Ru(bpy)(3)(2+) in the material is also revealed in optical spectroscopy where the ligand to metal charge transfer band appearing at lambda(max) 460 nm is observed. Also incorporation of MV(2+) leads to the observation of the charge transfer complex band with the titanate host from 350 to 650 nm. These solids are active for the photocatalytic hydrogen generation from water when colloidal platinum as catalyst and EDTA as sacrificial electron donor are present in the solution. The maximum efficiency was obtained for a solid consisting of layered titanate containing a 10.2 wt.% loading of Ru(bpy)(3)(2+) incorporated in the titanate layers and MV(2+) and Pt nanoparticles in the aqueous solution. This heterogeneous system produced about one-half the hydrogen generated for the conventional homogeneous system where all the components [Ru(bpy)(3)(2+), MV(2+), Pt, and EDTA] are in solution, with the advantage that it can be used as film or recovered by filtration from the aqueous medium. PMID- 20356603 TI - The seismoelectric effect: a nonisochoric streaming current 2. Theory and its experimental verification. AB - Propagation of ultrasound waves through a porous body saturated with liquid generates an electric response. This electroacoustic effect is called the "seismoelectric current"; the reverse phenomenon, where an electric field is the driving force, is known as the "electroseismic current". The seismoelectric current can be measured with existing electroacoustic devices that were originally designed to characterize liquid dispersions. The versatility of electroacoustic devices allows them to be calibrated using dispersions and then applied to the characterization of porous bodies. Here, we present the theory of the seismoelectric effect, which we derived by following the path suggested 65 years ago by Frenkel. To verify this theory, we measured the seismoelectric current generated by sediments of micrometer-sized silica particles. We demonstrated that the measurement allowed the determination of porosity of the sediment and the calculation of the zeta-potential. The zeta-potential value, calculated using the suggested theory, closely agreed with the value independently measured for moderately concentrated dispersions using a well-known electroacoustic theory for dispersions. Measurements of the seismoelectric effect with existing electroacoustic probes open up new ways for characterizing the porosity and zeta-potential of porous bodies, including ones with low permeability. PMID- 20356605 TI - Interaction of cement model systems with superplasticizers investigated by atomic force microscopy, zeta potential, and adsorption measurements. AB - Polyelectrolyte-based dispersants are commonly used in a wide range of industrial applications to provide specific workability to colloidal suspensions. Their working mechanism is based on adsorption onto the surfaces of the suspended particles. The adsorbed polymer layer can exercise an electrostatic and/or a steric effect which is responsible for achieving dispersion. This study is focused on the dispersion forces induced by polycarboxylate ether-based superplasticizers (PCEs) commonly used in concrete. They are investigated by atomic force microscopy (AFM) applying standard silicon nitride tips exposed to solutions with different ionic compositions in a wet cell. Adsorption isotherms and zeta potential analysis were performed to characterize polymer displacement in the AFM system on nonreactive model substrates (quartz, mica, calcite, and magnesium oxide) in order to avoid the complexity of cement hydration products. The results show that PCE is strongly adsorbed by positively charged materials. This fact reveals that, being silicon nitride naturally positively charged, in most cases the superplasticizer adsorbs preferably on the silicon nitride tip than on the AFM substrate. However, the force-distance curves displayed repulsive interactions between tip and substrates even when polymer was poorly adsorbed on both. These observations allow us to conclude that the dispersion due to PCE strongly depends on the particle charge. It differs between colloids adsorbing and not adsorbing PCE, and leads to different forces acting between the particles. PMID- 20356604 TI - Preparation of organic/inorganic composites by deposition of silica onto shell layers of polystyrene (core)/poly[2-(N,N-dimethylamino)ethyl methacrylate] (shell) particles. AB - Organic/inorganic composites were prepared by catalytic hydrolysis and subsequent condensation of tetraethoxysilane (TEOS) in a shell layer of core-shell polymer particles. First, core-shell particles were prepared by emulsifier-free emulsion polymerization of styrene (St) with 2-chloropropionyloxyethyl methacrylate (CPEM) using potassium persulfate as an initiator, followed by surface-initiated activator generated electron transfer-atom transfer radical polymerization (AGET ATRP) of 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA). Dynamic light scattering revealed that hydrodynamic diameter of the particle increased from 482 to 931 nm after AGET-ATRP of DMAEMA. The amount of grafted DMAEMA was determined to be ca. 10 mol% with respect to (wrt) St by (1)H NMR. Second, the composite particles were prepared by adding TEOS into a water/methanol dispersion of the P(St-CPEM)-g-P(DMAEMA). The P(St-CPEM)-g-P(DMAEMA)-SiO(2) composite particles containing ca. 50 wt.% of silica wrt the total weight were obtained. Hollow silica shell particles were also obtained by extraction of polymer components from the composites with tetrahydrofuran. PMID- 20356606 TI - The prevalence and risk factor analysis of silent brain infarction in patients with first-ever ischemic stroke. AB - BACKGROUND: To evaluate the prevalence and to identify the risk factors of silent brain infarction (SBI) in patients with ischemic stroke. METHODS: A total of 395 consecutive patients with first-ever ischemic stroke that underwent brain MRI were enrolled in this study. The prevalences of vascular risk factors in a SBI positive (n=132) and in a SBI-negative group (n=263) were compared. The prevalences and characteristics of SBI were further evaluated with respect to stroke subtype and periventricular white-matter hyperintensity (PWMH) lesion. RESULTS: The frequency of SBI among the 395 study subjects was 33.4%, and 10.1% of the study subjects had multiple-SBI lesions. The most common lesion site was basal ganglia (47%). Multiple logistic regression analysis showed that hypertension (OR: 1.94, 95% CI: 1.22-3.07, P=0.005) and the presence of an advanced PWMH lesion (OR: 1.77, 95% CI: 1.06-2.96, P=0.030) were significantly associated with SBI. Furthermore, an advanced PWMH lesion (OR: 2.88, 95% CI: 1.19 6.95, P=0.010) was more associated with multiple-SBI lesions than with a single SBI lesion. The frequency of SBI was higher among those with the small-vessel disease type (45.5%) than in those with the large-artery disease (32.5%) or cardioembolic stroke type (25.6%) (P=0.04). CONCLUSIONS: The prevalence of SBI in patients with ischemic stroke was found to be high, and hypertension was found to be the most important risk factor of SBI. Small-vessel disease and a diffuse white-matter lesion were found to be closely associated with SBI, and especially with multiple-SBI lesions. PMID- 20356607 TI - The Boston Harbor Project, and large decreases in loadings of eutrophication related materials to Boston Harbor. AB - Boston Harbor, a bay-estuary in the north-east USA, has recently been the site of one of the largest wastewater infrastructure projects conducted in the USA, the Boston Harbor Project (BHP). The BHP, which was conducted from 1991 to 2000, ended over a century of direct wastewater treatment facility discharges to the harbor. The BHP caused the loadings of total nitrogen (TN), total phosphorus (TP), total suspended solids (TSS) and particulate organic carbon (POC) to the harbor, to decrease by between 80% and 90%. Approximately one-third of the decreases in TSS and POC loadings occurred between 1991 and 1992; the remaining two-thirds, between 1995 and 2000. For TN and TP, the bulk of the decreases occurred between 1997 or 1998, and 2000. PMID- 20356608 TI - Does the survivorship of activated resting stages in toxic environments provide cues for ballast water treatment? AB - The toxic effects of three inorganic metals (Cu, Cr, Hg), three organic (phenol, formalin, ammonium) chemicals, ozone-enriched water and peroxides (H2O2) on embryonic development were tested in 8 species from the Porifera, Bryozoa and Crustacea. Toxicants with lower molecular weight showed stronger negative impacts on post-diapause embryos than chemicals with higher molecular weight if related to the toxicity of the chemicals to active adult stages. Only few embryos of the cladoceran Moina macrocopa and none of the cladoceran Wlassicsia pannonica treated with peroxides at concentration 0.3% developed further. Ozone-enriched water had no significant effect on post-diapause embryonic development in cladocerans. Ammonium (the product of NH4OH dissociation) in concentration 100 mg/l and higher killed all embryos of M. macrocopa inside protective membranes. Peroxides and ammonium are suggested for the purification of ship ballast waters as effective, non-expensive and non-persistent toxic chemicals. Resting stages of invertebrates including at least Crustaceans, Porifera and Bryozoa seem to allow not only dispersal among toxic industrial environments such as ship ballast compartments, but may also endure serious pollution events common in seaports and estuaries. Artemia cysts due to their strong protection against different toxic substances are recommended as a model for studies of toxic effects in diapausing stages in polluted estuaries and marine environments. PMID- 20356610 TI - What is the effect of rosiglitazone treatment on insulin secretory function in insulin-resistant individuals? It depends on how you measure it. AB - The goal of this study was to compare methods used to quantify the effect of rosiglitazone (RSG) on insulin secretory function, particularly estimates based on changes in fasting plasma glucose and insulin concentration vs daylong insulin responses to meals. To do this, we compared these measures of insulin secretion before and 3 months after RSG treatment in insulin-resistant individuals, subdivided into nondiabetic subjects (n = 29) and patients with type 2 diabetes mellitus (2DM) (n = 22). Insulin resistance was quantified by determining the steady-state plasma glucose concentration during the insulin suppression test and insulin secretory function by homeostasis model assessment of beta-cell function (HOMA-beta) and the total integrated daylong plasma insulin responses to mixed meals (insulin area under the curve). Baseline fasting and daylong plasma glucose concentrations were higher (P < .001) in patients with 2DM, associated with lower HOMA-beta values (P < .001). However, neither fasting nor daylong insulin concentrations after mixed meals differed in the 2 groups. Insulin sensitivity improved (P < .001) after RSG administration, with decreases of 31% +/- 23% and 21% +/- 14% in steady-state plasma glucose concentration in nondiabetic and diabetic subjects, respectively. Although fasting and daylong plasma glucose and insulin concentrations fell (P < .001) in both groups of RSG-treated individuals, HOMA-beta decreased in nondiabetic subjects and did not change in those with 2DM. In conclusion, RSG administration improved insulin sensitivity in both groups, associated with lower fasting and daylong glucose concentrations. Fasting and daylong insulin concentrations were also lower in both groups of RSG-treated subjects, but the values of HOMA-beta indicated either a decrease (nondiabetics) or no change (diabetics) in insulin secretory function. These results suggest that measurements of HOMA-beta may not provide a complete view of insulin secretory function, either when comparing diabetic with nondiabetic individuals or when assessing the response to RSG treatment in insulin-resistant individuals. PMID- 20356609 TI - [Recommendations for diagnosis, staging and treatment of pancreatic cancer (Part II)]. PMID- 20356611 TI - Phloridzin: biosynthesis, distribution and physiological relevance in plants. AB - The phenolic compound phloridzin (phloretin 2'-O-glucoside, phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. The apple tree (Malus sp.) accumulates high amounts of phloridzin, whereas few other species contain this compound only in low amounts. Additionally, Malus sp. show a species- and tissue specific distribution of phloridzin and its derivatives. Whereas the physiological role of phloridzin in planta is not fully understood, the effect on human health - especially diabetes - and membrane permeability is well documented. The biosynthesis of phloridzin was investigated only recently with recombinant enzymes and plant protein extracts and involved a NADPH-dependent dehydrogenase, chalcone synthase and UDP-glucose:phloretin 2'-O glycosyltransferase. PMID- 20356612 TI - Antiplasmodial benzophenone derivatives from the root barks of Symphonia globulifera (Clusiaceae). AB - In an effort to find antimalarial drugs, a systematic in vitro evaluation on a chloroquine-resistant strain of Plasmodium falciparum (FcB1) was undertaken on sixty plant extracts collected in French Guiana. The ethyl acetate extract obtained from the root barks of Symphonia globulifera exhibited a strong antiplasmodial activity (97% at 10 microg/ml). The phytochemical investigation of this extract led to the isolation of nine polycyclic polyprenylated acylphloroglucinol (PPAPs) compounds and two oxidized derivatives. All compounds showed antiplasmodial activity with IC(50)s ranged from 2.1 to 10.1 microM. A LC/ESI-MS(n) study performed on polyprenylated benzophenones previously isolated from Moronobea coccinea provided a reliable method for their detection in the extract and structural elucidation. PMID- 20356613 TI - [Open rhinoplasty. Evaluation of the results of 180 cases]. PMID- 20356614 TI - Prevalence of IgG antibodies against West Nile virus in blood donors during the 2003 outbreak in Tunisia. AB - This study aimed to evaluate the prevalence of anti-West Nile virus (WNV) IgG among two populations of Tunisian blood donors living in areas where human outbreaks of WNV have occurred. Cohorts A (Monastir) and B (Mahdia) included 742 and 102 blood donors respectively. Sera were tested by IgG ELISA test and results were confirmed by PRNT test. WNV neutralizing antibodies were detected in 32 (4.3%) and in 14 (13.7%) sera in cohorts A and B respectively. The prevalence of anti-WNV IgG was significantly higher in cohort B than in cohort A (P<0.001) and was significantly lower in females than in males (P<0.001). PMID- 20356615 TI - A prospective comparison of preperitoneal tension-free open herniorrhaphy with mesh plug herniorrhaphy for the treatment of femoral hernias. AB - BACKGROUND: Although many techniques exist for hernia repair, controversy still exists as to the best management of femoral hernias. We compared the preperitoneal approach with the mesh plug technique for the treatment of femoral hernias. METHODS: In this prospective study, 85 patients with primary unilateral femoral hernias were assigned randomly to a preperitoneal group (n = 45; 10 males, 35 females) and a mesh plug group (n = 40; 10 males, 30 females). Polypropylene patches or plugs were used, and all operations were performed by the same team. Patient demographics, recurrence rate, duration of hospital stay, and complications were recorded. The duration of follow-up ranged from 6 to 78 months. RESULTS: There were no differences between the groups with respect to operative time, postoperative duration of stay, pain assessed by visual analog scale, or wound infection rate. There were no recurrences in the preperitoneal group, whereas there were 4 (10%) recurrences in the mesh plug group. In the preperitoneal group, no patient complained of a foreign body sensation, whereas in the mesh plug group, 6 patients (15%) had the sensation of a "foreign body" in the groin. In the preperitoneal group, there were 2 cases (4%) of seroma that occurred 3 and 5 days after operation. In the mesh plug group, 8 cases (20%) of seroma occurred 3-7 days after operation. CONCLUSION: Preperitoneal herniorrhaphy seems to be associated with a lesser recurrence rate, less sensation of a foreign body postoperatively, and a lesser incidence of seroma formation compared with the mesh plug technique in the repair of femoral hernias. Preperitoneal herniorrhaphy provides better vision of the operative field, is flexible, and allows exploration of the inguinal canal during the procedure. PMID- 20356616 TI - Disinfection kinetics of murine norovirus using chlorine and chlorine dioxide. AB - We determined the disinfection efficiency of chlorine and chlorine dioxide (ClO(2)) using murine norovirus (MNV) and coliphage MS2 as surrogates for human norovirus. Experiments were performed in oxidant demand-free buffer (pH 7.2) at 5 degrees C and 20 degrees C. The extent of virus inactivation by a disinfectant was quantified using three different analytical methods: plaque, short template real-time TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR), and long template RT-PCR assays. Rapid inactivation of MNV by both chlorine and chlorine dioxide was observed by the plaque assay. According to the efficiency factor Hom model, Ct values of 0.314mg/Lmin and 0.247mg/Lmin were required for a 4-log reduction of MNV at 5 degrees C by chlorine and chlorine dioxide, respectively. Lower Ct values were required at 20 degrees C. Both long template and short template RT-PCR assays significantly underestimated the virus inactivation compared to the plaque assay. Our study demonstrates that adequate treatment of water with either chlorine or ClO(2) is likely to effectively control the waterborne transmission of human norovirus. PMID- 20356617 TI - Reduced NOx and PM10 emissions on urban motorways in The Netherlands by 80 km/h speed management. AB - A speed limit of 80 km/h with "strict enforcement" has been introduced in 2005 on zones of urban motorways in The Netherlands with the aim to improve air quality of NO(2) and PM(10) along these motorways. Strict enforcement means speed control by camera surveillance over the whole trajectory of 2-4 km combined with licence plate recognition and automatic fining in case of exceeding the speed limit. Traffic data measured in Rotterdam and Amsterdam at the zones without and with speed management showed that traffic dynamics have been significantly reduced as a result of speed management with strict enforcement. Reduction of traffic dynamics results in more free-flowing traffic with relatively less NO(x) and exhaust PM(10) emissions compared to congested traffic, i.e., stop-and-go traffic. The actual effect on NO(x) and PM(10) emissions at these speed management zones was studied in the cities Rotterdam and Amsterdam. The study was performed in two different ways: firstly by measurements and by modelling the contribution to NO(x) and PM(10) concentrations on both sides of the motorways, and secondly by estimating the change in traffic dynamics and the effect on emissions. From the results of both approaches in this study, it was concluded that in our case study in the Netherlands emission reduction by speed management is in the range of 5-30% for NO(x) and 5-25% for PM(10). Actual emission reductions by speed management at a specific motorway mainly depend on the ratio of congested traffic prior and after implementation of speed management. The larger this ratio, the larger is the relative emission reduction. The impact on air quality of 80 km/h for NO(x) and PM(10) is largest on motorways with a high fraction of heavy-duty vehicles. PMID- 20356618 TI - Assessment of hydrodissection, holmium:YAG laser vaporization of renal tissue, and both combined to facilitate laparoscopic partial nephrectomy in porcine model. AB - OBJECTIVES: To evaluate the modalities of electrocautery, holmium:yttrium aluminum-garnet (YAG) laser, hydrodissection, and combined holmium:YAG laser with hydrodissection applied to laparoscopic partial nephrectomy (LPN) in a porcine model. METHODS: A total of 16 Yorkshire pigs were divided into 4 equal groups (electrocautery, hydrodissection, holmium:YAG laser, and combined hydrodissection/holmium:YAG laser) and underwent unilateral LPN. The total operative time, partial nephrectomy time, hemostasis modality, and intraoperative complications were recorded. The pre- and postoperative hemoglobin was measured. Abdominal computed tomography was performed 2 weeks postoperatively. Representative specimens from each arm were examined for histologic findings. RESULTS: The mean total operative time and the time to perform partial nephrectomy was lower for the combined hydrodissection/holmium:YAG laser arm (66 minutes and 13 minutes, respectively) compared with the electrocautery arm (93 and 30 minutes, respectively), holmium:YAG laser-only arm (77 and 19 minutes, respectively), and hydrodissection-only arm (129 and 35 minutes, respectively). The mean decrease in hemoglobin was the least for the combined hydrodissection/holmium:YAG laser arm (5.3 g/L) followed by the holmium:YAG-only (15.3 g/L), hydrodissection-only (16.8 g/L), and electrocautery (35.5 g/L) arms, respectively. The histologic examination demonstrated an increased depth of tissue injury in the electrocautery arm. CONCLUSIONS: In a porcine model, the combined use of the hydrodissection/holmium:YAG laser to perform LPN had the shortest operative time and the lowest decrease in hemoglobin and appears to warrant additional clinical evaluation in human trials for LPN. PMID- 20356619 TI - Microparticulate ice slurry for renal hypothermia: laparoscopic partial nephrectomy in a porcine model. AB - OBJECTIVES: Previously, we described the feasibility of renal hypothermia using microparticulate ice slurry during laparoscopy. In the present study, we compared surface cooling with the ice slurry versus near-frozen saline or warm ischemia (WI) during laparoscopic partial nephrectomy (LPN) in a porcine model. METHODS: We used a single-kidney porcine model. Animals in 5 equal groups (n = 6 each) underwent right laparoscopic complete nephrectomy. In Phase I, left LPN was performed under 90 minutes of ischemia and 90-minute renal cooling with either slurry (Slurry group 1) or saline (Saline group 1). No cooling was applied in the WI group. In Phase II, to simulate more extreme condition, ischemia time was extended to 120 minutes and cooling shortened to 10 minutes (Slurry group 2 and Saline group 2). The study endpoints were renal and core temperature during the surgery and serum creatinine at baseline and days 1, 3, 7, and 14 after the procedure. RESULTS: The ice slurry was easily produced and delivered. Nadir renal temperature (mean +/- SD) was 8 +/- 4 degrees C in Slurry group 1 vs. 22.5 +/- 3 degrees C in Saline group 1 (P < .0001). Renal rewarming to 30 degrees C occurred after 61 +/- 7 minutes in Slurry group 2 vs. 24 +/- 6 minutes in Saline group 2 (P < .0001). Core temperature decreased on average to 35 degrees C in the Saline groups compared with 37 degrees C in the Slurry groups (P < .0001). Serum creatinine did not differ between the Saline and Slurry groups in Phases I and II at any time point. CONCLUSIONS: Ice slurry provides superior renal cooling compared with near-frozen saline during LPN without associated core hypothermia. PMID- 20356620 TI - Screening for type 2 diabetes--where are we now? PMID- 20356621 TI - Age at initiation and frequency of screening to detect type 2 diabetes: a cost effectiveness analysis. AB - BACKGROUND: No clinical trials have assessed the effects or cost-effectiveness of sequential screening strategies to detect new cases of type 2 diabetes. We used a mathematical model to estimate the cost-effectiveness of several screening strategies. METHODS: We used person-specific data from a representative sample of the US population to create a simulated population of 325,000 people aged 30 years without diabetes. We used the Archimedes model to compare eight simulated screening strategies for type 2 diabetes with a no-screening control strategy. Strategies differed in terms of age at initiation and frequency of screening. Once diagnosed, diabetes treatment was simulated in a standard manner. We calculated the effects of each strategy on the incidence of type 2 diabetes, myocardial infarction, stroke, and microvascular complications in addition to quality of life, costs, and cost per quality-adjusted life-year (QALY). FINDINGS: Compared with no screening, all simulated screening strategies reduced the incidence of myocardial infarction (3-9 events prevented per 1000 people screened) and diabetes-related microvascular complications (3-9 events prevented per 1000 people), and increased the number of QALYs (93-194 undiscounted QALYs) added over 50 years. Most strategies prevented a significant number of simulated deaths (2-5 events per 1000 people). There was little or no effect of screening on incidence of stroke (0-1 event prevented per 1000 people). Five screening strategies had costs per QALY of about US$10,500 or less, whereas costs were much higher for screening started at 45 years of age and repeated every year ($15,509), screening started at 60 years of age and repeated every 3 years ($25,738), or a maximum screening strategy (screening started at 30 years of age and repeated every 6 months; $40,778). Several strategies differed substantially in the number of QALYs gained. Costs per QALY were sensitive to the disutility assigned to the state of having diabetes diagnosed with or without symptoms. INTERPRETATION: In the US population, screening for type 2 diabetes is cost effective when started between the ages of 30 years and 45 years, with screening repeated every 3-5 years. FUNDING: Novo Nordisk, Bayer HealthCare, [corrected] and Pfizer. PMID- 20356622 TI - The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension. AB - Tendon fibroblasts synthesize collagen and form fibrils during embryonic development, but to what extent mature fibroblasts are able to recapitulate embryonic development and develop normal tendon structure is unknown. The present study examined the capability of mature human tendon fibroblasts to initiate collagen fibrillogenesis when cultured in fixed-length fibrin gels. Fibroblasts were dissected from semitendinosus and gracilis tendons from healthy humans and cultured in 3D linear fibrin gels. The fibroblasts synthesized an extracellular matrix of parallel collagen fibrils that were aligned along the axis of tension. The fibrils had a homogeneous narrow diameter that was similar to collagen fibrils occurring in embryonic tendon. Immunostaining showed colocalization of collagen type I with collagen III, XII and XIV. A fibronectin network was formed in parallel with the collagen, and fibroblasts stained positive for integrin alpha(5). Finally, the presence of cell extensions into the extracellular space with membrane-enclosed fibrils in fibripositors indicated characteristics of embryonic tendon. We conclude that mature human tendon fibroblasts retain an intrinsic capability to perform collagen fibrillogenesis similar to that of developing tendon, which implies that the hormonal/mechanical milieu, rather than intrinsic cellular function, inhibits regenerative potential in mature tendon. PMID- 20356624 TI - Concomitant use of imatinib and warfarin in chronic phase chronic myeloid leukemia patients does not interfere with drug efficacy. PMID- 20356623 TI - Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy. AB - Rough titanium (Ti) surface microarchitecture and high surface energy have been shown to increase osteoblast differentiation, and this response occurs through signaling via the alpha(2)beta(1) integrin. However, clinical success of implanted materials is dependent not only upon osseointegration but also on neovascularization in the peri-implant bone. Here we tested the hypothesis that Ti surface microtopography and energy interact via alpha(2)beta(1) signaling to regulate the expression of angiogenic growth factors. Primary human osteoblasts (HOB), MG63 cells and MG63 cells silenced for alpha(2) integrin were cultured on Ti disks with different surface microtopographies and energies. Secreted levels of vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (FGF-2), epidermal growth factor (EGF), and angiopoietin-1 (Ang-1) were measured. VEGF-A increased 170% and 250% in MG63 cultures, and 178% and 435% in HOB cultures on SLA and modSLA substrates, respectively. In MG63 cultures, FGF-2 levels increased 20 and 40-fold while EGF increased 4 and 6-fold on SLA and modSLA surfaces. These factors were undetectable in HOB cultures. Ang-1 levels were unchanged on all surfaces.Media from modSLA MG63 cultures induced more rapid differentiation of endothelial cells and this effect was inhibited by anti-VEGF-A antibodies. Treatment of MG63 cells with 1 alpha,25(OH)(2)D3 enhanced levels of VEGF-A on SLA and modSLA.Silencing the alpha(2) integrin subunit increased VEGF-A levels and decreased FGF-2 levels. These results show that Ti surface microtopography and energy modulate secretion of angiogenic growth factors by osteoblasts and that this regulation is mediated at least partially via alpha(2)beta(1) integrin signaling. PMID- 20356625 TI - Chronic lymphocytic leukemia/small lymphocytic lymphoma with focal D-type cyclin expression in proliferation centers: a report of four cases. PMID- 20356626 TI - Effectiveness of a parent training program "Incredible Years" in a child protection service. AB - OBJECTIVE: This study aims to evaluate the effectiveness of a parent training program in improving parenting practices, parents' feeling of self-efficacy and parents' perception of their child's behavior, implemented in a child protection service, with trained professionals from the agency acting as facilitators. METHOD: Thirty-five parents monitored in a child protection service for child neglecting behaviors participated either in the intervention group (n=26) or were on the waiting list (n=9). The program implemented (Incredible Years) lasted 16 weeks, was in a group format, and aimed: (1) to develop a harmonious parent-child relationship; (2) to support parents in learning and consistently applying effective practices; (3) to improve problem solving and communication skills within families and with teachers. A repeated measures design was used to test the program's effects on parenting practices, parents' feeling of self-efficacy, parents' perception of their child's behavior, and parents' satisfaction. Parents were tested twice, during a 19-week interval, before and after the parent training program. RESULTS: Analyses of variance comparing Intervention and Control groups with repeated measures (pre- and post-test measures) revealed that the program has a positive impact on parenting practices (harsh discipline, physical punishment, praise/incentive, appropriate discipline and positive verbal discipline) and parents' perception of their child's behavior (frequency of behavioral problems and number of problematic behaviors). No change on clear expectations from parents, or on parents' self-efficacy was observed. CONCLUSION: Though the implementation of an evidence-based parent training program by professionals in a child protection service presents specific challenges, results suggest that it can contribute to improvements in parenting practices and in parents' perception of their child's behavior. PMID- 20356627 TI - The rainbow trout (Oncorhynchus mykiss) interferon response in the ovary. AB - Immune responses in the ovary are tightly regulated to provide protection for the developing germ cells, which are very sensitive to inflammatory responses. This characteristic immune response is often used by viral pathogens to evade the immune system, replicate and be transmitted to other specimens through the ovary. Taking into account that in teleost fish, the innate immune system is considered crucial to the outcome of viral infections and the interferon (IFN) system is considered as the first line of defence against viruses, we have studied the IFN response in rainbow trout (Oncorhynchus mykiss) ovary using two viruses with different replicative capacity in this organ, namely viral haemorrhagic septicaemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Both VHSV and IPNV are shed from the ovary, but while VHSV actively replicates at this site, IPNV remains silent. In this context, we have determined the levels of expression of IFNs and the IFN-induced Mx genes in the ovary upon in vivo and in vitro infections with VHSV and IPNV, and compared to the effects provoked by the viral mimic poly I:C in vivo. We have demonstrated that while VHSV strongly up regulates all the IFN genes studied, IPNV in vivo exposure either has no effect or even provokes strong suppression of IFN gene expression. These differences are not observed in vitro, even though IPNV does not replicate actively in this case either. Finally, to better understand the role that the production of type I IFN plays in the ovary, we have studied the effects of two type I recombinant rainbow trout IFNs (rtIFN1 and rtIFN2) to modulate both the expression of immune genes and to establish an antiviral state in the ovary. Interestingly, the ovary was able to respond to both rtIFN1 and 2, despite the fact that the IFN1 gene was not expressed here. Moreover, rtIFN1 and rtIFN2 not only modulated the expression of genes related to the IFN response, but also modulated inflammatory genes and significantly suppressed VHSV replication. PMID- 20356628 TI - Molecular analysis of multicatalytic monoclonal antibodies. AB - Recently, our first report demonstrated that Cucumber mosaic virus (CMV)-specific monoclonal antibodies (mAbs) possess DNase-like activity against DNA. In the present study, we show for the first time ever how one mAb (mAb-5) has polyreactive (protease, DNase, and RNase) catalytic activities (catAbs). Amino acid sequence analysis of the encoded variable-genes showed that the light chains of the hybridomas expressed the germline family genes V kappa 1A, bb1.1 and V kappa II, bd2, whose protease and DNase catalytic activities have been reported, while the heavy chain genes were expressed in several germline families (eight of V(H)1/J558, three of V(H)5/V(H)7183, and three of V(H)8/V(H)3609). Interestingly, these germline genes have been well studied in esterolytic antibodies. Here we present for the first time convincing evidence showing that highly purified mAb-5 catalyze both single- and double-stranded DNA and exhibit RNase and protease activity. The greatest therapeutic potential of catAbs could lie in selective prodrug activation. Furthermore, catAbs offer excellent or unique specificity for individual and defined antigenic targets. Therefore, the phenomenon of autoantibody catalysis can potentially be applied to isolate efficient catalytic domains directed against pathogenetically and clinically relevant autoimmune epitopes. PMID- 20356629 TI - Synthesis, structure and characterization of novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide Antiproliferative activity of the synthesized complexes and related selenosemicarbazone complexes. AB - Two novel Cd(II) and Zn(II) complexes with the condensation product of 2 formylpyridine and selenosemicarbazide were synthesized. The structure of Cd(II) complex was determined by X-ray crystallography. The ligand is coordinated in a neutral form via pyridine and azomethine nitrogen atoms and the selenium donor. The cadmium ion completes its five-coordination by two chloride ligands, forming a square-pyramidal geometry. The structure of Zn(II) complex was established by analysis of spectroscopic data, which indicated coordination of the ligand as a bidentate via the selenium and the azomethine nitrogen atoms. The cytotoxic activity of the newly synthesized complexes, as well as if five structurally related complexes and the ligand evaluated against eight tumor cell lines. The new Cd(II) complex showed the highest activity similar to cisplatin with IC50 less than 10muM for all cell lines. Cell cycle distribution and apoptosis study showed that Cd(II) complex and cisplatin might have some similarity in anticancer activity, which was not the case for cisplatin and other studied complexes. Effects of the complexes on matrix metalloproteinases (MMPs) MMP-9 and MMP-2 was also studied. Cd(II) and Zn(II) complexes and cisplatin increased MMP-2 activity in supernatants of tested cells, while Ni(II) complex with the same ligand decreased the activity, implying a possible activity in preventing tumor invasion and metastasis processes. PMID- 20356630 TI - Ultrahigh (0.93A) resolution structure of manganese peroxidase from Phanerochaete chrysosporium: implications for the catalytic mechanism. AB - Manganese peroxidase (MnP) is an extracellular heme enzyme produced by the lignin degrading white-rot fungus Phanerochaete chrysosporium. MnP catalyzes the peroxide-dependent oxidation of Mn(II) to Mn(III). The Mn(III) is released from the enzyme in complex with oxalate, enabling the oxalate-Mn(III) complex to serve as a diffusible redox mediator capable of oxidizing lignin, especially under the mediation of unsaturated fatty acids. One heme propionate and the side chains of Glu35, Glu39 and Asp179 have been identified as Mn(II) ligands in our previous crystal structures of native MnP. In our current work, new 0.93A and 1.05A crystal structures of MnP with and without bound Mn(II), respectively, have been solved. This represents only the sixth structure of a protein of this size at 0.93A resolution. In addition, this is the first structure of a heme peroxidase from a eukaryotic organism at sub-Angstrom resolution. These new structures reveal an ordering/disordering of the C-terminal loop, which is likely required for Mn binding and release. In addition, the catalytic Arg42 residue at the active site, normally thought to function only in the peroxide activation process, also undergoes ordering/disordering that is coupled to a transient H bond with the Mn ligand, Glu39. Finally, these high-resolution structures also reveal the exact H atoms in several parts of the structure that are relevant to the catalytic mechanism. PMID- 20356631 TI - Interaction between HLA-G and monocyte/macrophages in human pregnancy. AB - Several lines of evidence suggest that the human leukocyte antigen (HLA)-G play a key role in the regulation of human pregnancy. A sub-population of cells highly represented at the decidua belong to the myeloid-derived monocyte/macrophage lineage, which potentially interact with HLA-G expressing cells. It is proposed that HLA-G protects decidual trophoblasts from lysis by blocking the effector function of decidual monocyte/macrophages. The interaction between HLA-G and monocyte/macrophages may therefore contribute to a successful pregnancy. Here we examine existing knowledge on the convergent role of HLA-G and monocyte/macrophages in pregnancy and define the synergy that exists between these two elements in the decidua. Key features of the HLA-G gene product are discussed followed by the main characteristics of decidual monocyte/macrophages. A hypothetical model for the interaction between HLA-G and monocyte/macrophage cells at the fetal-maternal interface is proposed. PMID- 20356632 TI - Cordance or antidepressant treatment response (ATR) index? PMID- 20356633 TI - A new strategy of immune evasion by influenza A virus: inhibition of monocyte differentiation into dendritic cells. AB - Dendritic cells (DC) play a versatile role in orchestrating immune responses against influenza virus. During inflammation or infection, monocytes preferentially differentiate to generate DCs. Here, we demonstrate that in vitro infection of monocytes with influenza virus impairs their development into DCs. Influenza infection of monocytes, pre-treated with GM-CSF and IL-4 for DC differentiation, was minimally productive and non-cytopathic. In spite of successful viral genome transcription, viral protein synthesis was restricted at an early stage. However, despite the limited replication, influenza infected monocytes failed to develop distinctive DC-like morphologies. Infected cells expressed reduced amounts of CD11c, CD172a, CD1w2 and CCR5. Antigen endocytosis by infected monocytes was also affected. Cytokine expression profiles were also modified which was conducive for arresting DC differentiation. At least limited viral replication was necessary for complete inhibition of differentiation. This identifies a new strategy by influenza virus to interfere with DC differentiation and evade virus specific immune responses. PMID- 20356634 TI - Effect of cerebellar fastigial nuclear lesions on differentiation and function of thymocytes. AB - We have previously shown that the cerebellum regulates functions of T, B and natural killer (NK) cells. Herein, we provide further evidence for cerebellar immunomodulation at the profiles of differentiation and maturation of thymocytes and function of mature T lymphocytes. Neuronal bodies of the fastigial nuclei (FN), one of three cerebellar nuclei, were damaged by microinjection of kainic acid (KA) in the bilateral FN. On days 12 and 32 following the KA injection, percentages of thymocyte subpopulations including CD4(-)CD8(-), CD4(+)CD8(+), CD4(+)CD8(-) and CD4(-)CD8(+) cells, apoptotic DNA fragmentation of thymocytes, and levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the serum were measured by flow cytometry, diphenylamine assay and enzyme-linked immunosorbent assay (ELISA), respectively. In the thymus, the percentage of CD4(+)CD8(-) cells in thymocyte population was elevated by the cerebellar FN lesions on both the 12th and the 32nd days post-lesion. The other thymocyte subsets only significantly changed at the late time point (day 32) post-lesion, with an increase in CD4(-)CD8(-) cells and a decrease in CD4(+)CD8(+) thymocytes relative to control rats with intact FN or saline-infused FN. The cerebellar FN lesions, regardless of the 12th or the 32nd day post-lesion, reduced the percentage of thymocyte DNA fragmentation and elevated the concentrations of IFN gamma and IL-4 in the serum. However, the cerebellar cortex lesions, as an additional control to show the specificity of the FN-lesion results, did not significantly alter the differentiation and apoptosis of thymocytes. These results reveal that the cerebellar FN lesions accelerate the differentiation of thymocytes into mature helper T lymphocytes in the thymus and enhance function of the helper T cells in the peripheral immune tissue. Collectively, these findings suggest a substantial modulation of immune system by the cerebellum. PMID- 20356635 TI - Towards a molecular understanding of sex differences in memory formation. AB - Sex differences exist in brain function and behavior. However, the underlying molecular mechanisms are only beginning to emerge. Recent studies in rodents have revealed molecular mechanisms underlying sex differences in memory formation. It is becoming clear that sex differences are not simply reflective of differences in sex hormones, but also reflect distinctions in synaptic signaling mechanisms including the role of synaptic kinases. Furthermore, there are sex differences in the activation of transcription factors and gene transcription during memory formation. This review discusses emerging evidence in the field and how these findings are providing a first step towards a molecular understanding of how sex differences impact on memory formation both in health and disease. PMID- 20356636 TI - Bcl-2 and Caspase 3 mRNA levels in the testes of gudgeon, Gobio gobio, exposed to ethinylestradiol (EE2). AB - Apoptosis inhibition has been reported in the male reproductive tract of teleost fish exposed to 17beta-estrogen or estrogen-like compounds. In order to understand the molecular mechanisms of cell death inhibition, this study examined 2 genes involved in the apoptotic pathway, Bcl-2 and Caspase 3, an anti-apoptotic and a pro-apoptotic genes, respectively. Partial cDNA sequences of Bcl-2 and Caspase 3 were cloned from gudgeon (Gobio gobio), a common European cyprinid fish. To follow mRNA levels of Bcl-2 and Caspase 3 under xenoestrogen exposure, we first performed an in vitro experiment on fish testis exposed to the most potent xenoestrogen found in the environment, ethinylestradiol (EE2). We further studied mRNA expression of both genes in the testis of fish exposed to xenoestrogens in situ. In the in vitro experiment, fragments of gudgeon testis were exposed for 21 days to 10(-3), 10(-2), 10(-1), 1 and 10 microg/L of EE2, as well as to positive (10(-1) microg/L of E2) and ethanol control medium. Results showed a significant induction of Bcl-2 mRNA at 10(-1) microg/L (p<0.05). Surprisingly, Caspase 3, a cell death effector, displayed the same profile as observed for the anti-apoptotic gene Bcl-2. In the experiment on wild gudgeon exposed from birth to an estrogenic sewage treatment plant effluent, the mRNA expression of Bcl-2 and Caspase 3 in feminized fish (ovotestis) was not significantly different due to high variability of expression between individuals. At the current state of knowledge on spermatogenesis disruption in teleost fish, in vitro studies seem better adapted than in situ investigations to enlighten the molecular pathway of apoptosis inhibition in testis exposed to xenoestrogens. PMID- 20356637 TI - Toxicity of aromatic compounds to Tetrahymena estimated by microcalorimetry and QSAR. AB - The toxicity of six organic aromatic chemicals to Tetrahymena growth metabolism was studied by microcalorimetry. The growth constant k, inhibitory ratio I, and half-inhibiting concentration IC(50) were calculated. The results suggested that the order of toxicity was aniline>nitrobenzene>chlorobenzene>toluene>benzene>phenol. Based on the molecular descriptors (such as K(OW), E(HOMO), E(LUMO), DeltaE, E(T) and logIC(50)), the QSAR equation is obtained by multiple linear regression analysis: logIC(50)= 3.360-1.545 E(HOMO)-0.6850 DeltaE-0.3019logK(OW) (R=0.8643, n=6, s=0.202, F=0.739, Sig.=0.041, R(CV)(2)=0.624). The equation indicates that the toxic action is a two-step process: the pass of the chemicals through the cell membrane (described by logK(OW)) and the electron-transfer reaction of the chemicals with biomolecules (described by E(HOMO) and DeltaE). The substituents on aromatic ring are crucial to the toxicity of the compounds and the reaction between the chemicals and biological macromolecules is important. PMID- 20356638 TI - Differential effects of delirium on fluid and crystallized cognitive abilities. AB - Patients with delirium (acute confusional state) show extensive cognitive deficits. These deficits have typically been measured using tests of fluid cognition, which involve the active processing of mental representations. However, the effects of delirium on stored, crystallized dimensions of cognition, such as well-learnt word pronunciation knowledge, are not known. In this study 37 patients (aged 60-85 years) without delirium were recruited before undergoing cardiac surgery. Cognitive assessments were performed 0-8 days before surgery and again 2-9 days after surgery in order to determine the effects of post-operative delirium (POD) on fluid and crystallized aspects of cognition. Crystallized cognition was tested with the National Adult Reading Test (NART). Fluid cognition was tested with digit span, verbal fluency and Stroop tests. Nine patients (24%) developed delirium post-operatively. Patients with delirium showed significant post-operative deficits on most tests of fluid cognition, but no change in the NART measure of crystallized cognition (p=0.95). These results parallel recent findings in Alzheimer's dementia and suggest that, despite showing extensive deficits of fluid cognitive processing, crystallized cognition is preserved in delirium. The results also suggest that the NART may be a useful tool for assessing premorbid ability in patients with delirium. PMID- 20356639 TI - Impact of calcification length ratio on the intervention for chronic total occlusions. AB - BACKGROUND: The 64-multislice computed tomography (MSCT) can be used to directly guide the complex percutaneous coronary intervention (PCI) procedure and predict the outcome. This study aimed to determine the possibility of success of angioplasty for chronic total occlusion (CTO) performed on the basis of MSCT results. METHODS: In this study, we assessed 82 de novo CTO lesions in 67 patients, who were subjected to 64-MSCT before undergoing PCIs. The lesions were either treated with an antegrade approach or a combined bilateral antegrade and retrograde approach. The clinical characteristics of the patients and the angiographic and 64-MSCT parameters associated with the intervention result were analyzed. RESULTS: In this study, the technical and procedural success rates were 89.0% and 80.5%, respectively. There were significant differences in heavy calcification with the calcification length ratio of >0.5, proximal stump calcification, and distal stump calcification between the technical-success and technical-failure groups (P<0.001, P=0.022, and P=0.003, respectively) as well as between the procedural-success and procedural-failure groups (P<0.001, P=0.042, and P=0.014, respectively). Multivariate analysis showed that heavy calcification was the strong independent parameter that not only influenced technical success (odds ratio [OR]=0.040, 95% confidence interval [CI]=0.006-0.254, P=0.001) but also procedural success (OR=0.127, 95% CI=0.035-0.461, P=0.002). CONCLUSIONS: Calcification length ratio of >0.5 remains to be the independent negative predictor of both technical and procedural success. PMID- 20356640 TI - Estimating animal movement contacts between holdings of different production types. AB - Animal movement poses a great risk for disease transmission between holdings. Heterogeneous contact patterns are known to influence the dynamics of disease transmission and should be included in modeling. Using pig movement data from Sweden as an example, we present a method for quantification of between holding contact probabilities based on different production types. The data contained seven production types: Sow pool center, Sow pool satellite, Farrow-to-finish, Nucleus herd, Piglet producer, Multiplying herd and Fattening herd. The method also estimates how much different production types will determine the contact pattern of holdings that have more than one type. The method is based on Bayesian analysis and uses data from central databases of animal movement. Holdings with different production types are estimated to vary in the frequency of contacts as well as in what type of holding they have contact with, and the direction of the contacts. Movements from Multiplying herds to Sow pool centers, Nucleus herds to other Nucleus herds, Sow pool centers to Sow pool satellites, Sow pool satellites to Sow pool centers and Nucleus herds to Multiplying herds were estimated to be most common relative to the abundance of the production types. We show with a simulation study that these contact patterns may also be expected to result in substantial differences in disease transmission via animal movements, depending on the index holding. Simulating transmission for a 1 year period showed that the median number of infected holdings was 1 (i.e. only the index holding infected) if the infection started at a Fattening herd and 2161 if the infection started on a Nucleus herd. We conclude that it is valuable to include production types in models of disease transmission and the method presented in this paper may be used for such models when appropriate data is available. We also argue that keeping records of production types is of great value since it may be helpful in risk assessments. PMID- 20356642 TI - Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes. AB - BACKGROUND: Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. METHODS: We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. RESULTS: Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. CONCLUSIONS: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. PMID- 20356641 TI - Maternal employment and the health of low-income young children. AB - This study examines whether maternal employment affects the health status of low income, elementary-school-aged children using instrumental variables estimation and experimental data from a welfare-to-work program implemented in the early 1990s. Maternal report of child health status is predicted as a function of exogenous variation in maternal employment associated with random assignment to the experimental group. IV estimates show a modest adverse effect of maternal employment on children's health. Making use of data from another welfare-to-work program we propose that any adverse effect on child health may be tempered by increased family income and access to public health insurance coverage, findings with direct relevance to a number of current policy discussions. In a secondary analysis using fixed effects techniques on longitudinal survey data collected in 1998 and 2001, we find a comparable adverse effect of maternal employment on child health that supports the external validity of our primary result. PMID- 20356643 TI - Differences in motor learning success are associated with differences in M1 excitability. AB - Primary motor cortex (M1) plays a role in motor learning, although the exact nature of that involvement remains unclear. The present study examined the relationship between motor learning and cortical plasticity by manipulating augmented feedback during motor training. Two groups of 10 participants performed a wrist flexion-extension waveform-tracking task with either concurrent and terminal augmented feedback after every trial (100% FB) or only terminal feedback after every alternate trial (50% FB). Single- and paired-pulse transcranial magnetic stimulation (TMS) was used to assess cortical excitability short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) before, after, and 24 h following (retention) motor training. The 50% FB group performed better at retention than the 100% FB group, indicative of enhanced learning due to reduced FB scheduling. Cortical excitability did not change during acquisition for either group, however, the 50% FB group had elevated M1 excitability at retention, suggesting M1 involvement in the consolidation of learning. Reduced SICI following practice suggests a reduction of intracortical inhibition during motor skill acquisition. ICF was unchanged. It is concluded that the nature of M1 modulation associated with the acquisition and retention of a novel motor skill appears to vary with the nature and complexity of task requirements. PMID- 20356644 TI - Detoxification of aflatoxin B1 and patulin by Enterococcus faecium strains. AB - Aim of the present study was to investigate the detoxification of aflatoxin B(1) and patulin from aqueous solution by probiotic culture of Enterococcus faecium M74 and commercial culture of E. faecium EF031. The effect of the bacterial viability, incubation time and pH of the medium on the binding ability was tested. Also, binding stability was determined by washing the bacteria-mycotoxin complexes with phosphate buffer saline. Both M74 and EF031 strains have the ability to remove aflatoxin B(1) and patulin. While M74 removes 19.3 to 30.5% of aflatoxin B(1) and 15.8 to 41.6% of patulin, EF031 removes 23.4 to 37.5% of aflatoxin B(1) and 19.5 to 45.3% of patulin throughout a 48 h incubation period. The removal of aflatoxin B(1) and patulin was highest at pH 7.0 and 4.0, respectively. The stability of the aflatoxin B(1) and patulin complexes formed with the bacterial strains was found to be high. The viability of the bacteria did not have any significant effect on the detoxification of aflatoxin B(1) and patulin. Detoxification properties of E. faecium could represent new strategies for a possible application in the human diet and animal feed. PMID- 20356645 TI - Feed supplementation of Lactobacillus plantarum PCA 236 modulates gut microbiota and milk fatty acid composition in dairy goats--a preliminary study. AB - This study aimed to evaluate the potential of a promising Lactobacillus plantarum isolate (PCA 236) from cheese as a probiotic feed supplement in lactating goats. The ability of L. plantarum to survive transit through the goat gastrointestinal tract and to modulate selected constituents of the gut microbiota composition, monitored at faecal level was assessed. In addition, L. plantarum effects on plasma immunoglobulins and antioxidant capacity of the animals as well as on the milk fatty acid composition were determined. For the purpose of the experiment a field study was designed, involving 24 dairy goats of the Damascus breed, kept in a sheep and goat dairy farm. The goats were divided in terms of body weight in two treatments of 12 goats each, namely: control (CON) without addition of L. plantarum and probiotic (PRO) treatment with in feed administration of L. plantarum so that the goats would intake 12 log CFU/day. The experiment lasted 5 weeks and at weekly time intervals individual faecal, blood and milk samples were collected and analysed. All faecal samples were examined for the presence of L. plantarum PCA 236. In addition, the culturable population levels of mesophilic aerobes, coliforms lactic acid bacteria (LAB), Streptococcus, Enterococcus, mesophilic anaerobes, Clostridium and Bacteroides in faeces were also determined by enumeration on specific culture media. In parallel, plasma IgA, IgM and IgG and antioxidant capacity of plasma and milk were determined. No adverse effects were observed in the animals receiving the lactobacillus during the experiment. Lactobacillus plantarum PCA 236 was recovered in the faeces of all animals in the PRO treatment. In addition, PRO treatment resulted in a significant (P2 microg/mL] and moxifloxacin (MIC >1 microg/mL) was found in 20 (41.7%) and 21 (43.8%) isolates, respectively. High level levofloxacin and moxifloxacin resistance (MIC >32 microg/mL) was detected in 19 (39.6%) and 15 (31.3%) isolates, respectively. Among 150 residents, those with urinary catheterisation (P=0.018) and tracheostomy tubes (P=0.029) were independently associated with airway colonisation by moxifloxacin-resistant H. influenzae. Among 30 residents with carriage of H. influenzae, no factor was significantly associated with moxifloxacin resistance. Pulsed-field gel electrophoresis of the isolates revealed 14 distinct types. Two major clones accounted for 29 isolates, 27 of which were obtained from 13 residents in one nursing home. All but two of the fluoroquinolone-resistant isolates belonged to these two major clones. This study highlights the emergence of fluoroquinolone-resistant H. influenzae and its clonal spread among nursing home residents in southern Taiwan. Further studies on clinical implications and the extent of fluoroquinolone non-susceptibility and resistance are needed. PMID- 20356652 TI - [Confocal endomicroscopy: should we change our approach to the endoscopic diagnosis of the mucosal lesions of the gastrointestinal tract?]. PMID- 20356653 TI - [Hip fracture in the elderly]. PMID- 20356650 TI - Enteric reovirus infection stimulates peanut-specific IgG2a responses in a mouse food allergy model. AB - IgE-mediated food allergies are an important cause of life-threatening hypersensitivity reactions. Orally administered peanut antigens mixed with the mucosal adjuvant cholera toxin (CT) induce a strong peanut extract (PE)-specific serum IgE response that is correlated with T-helper type 1 (Th1) and type 2 (Th2) like T-cell responses. This study was conducted to determine if respiratory enteric orphan virus (reovirus), a non-pathogenic virus that induces robust Th1 mediated mucosal and systemic responses could modulate induction of PE-specific allergic responses when co-administered with PE. Young mice were orally exposed to PE mixed with CT, reovirus, or both CT and reovirus. As expected, CT promoted PE-specific serum IgE, IgG1, and IgG2a and intestinal IgA production as well as splenic Th1- and Th2-associated cytokine recall responses. Reovirus did not alter PE-specific serum IgE and IgG1 levels, but substantially increased the PE specific IgG2a response when co-administered with PE with or without CT. Additionally, reovirus significantly decreased the percentage of the Peyer's patch CD8+ T-cells and Foxp3+CD4+ T-regulatory cells when co-administered with PE. These results demonstrate that an acute mucosal reovirus infection and subsequent Th1 immune response is capable of modulating the Th1/Th2 controlled humoral response to PE. The reovirus-mediated increase in the PE-specific IgG2a antibody response may have therapeutic implications as increased levels of non allergenic PE-specific IgG2a could block PE antigens from binding to IgE sensitized mast cells. PMID- 20356654 TI - [Towards an update of the SMAQ questionnaire]. PMID- 20356655 TI - Novel benzimidazole-pyrimidine conjugates as potent antitumor agents. AB - As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((1H-benzo[d]imidazol-2-yl)methylthio)-4-(substituted)-6 phenylpyrimidine-5-carbonitriles was synthesized. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against twelve cell lines namely, Cervical carcinoma (KB), Ovarial carcinoma (SK OV-3), CNS cancer (SF-268), Non small lung cancer (NCI H460), Colonadenocarcinoma (RKOP27), Leukaemia (HL60, U937, K562), Melanoma (G361, SK-MEL-28) and Neuroblastoma (GOTO, NB-1) revealed their marked potency when compared with known anticancer drugs. PMID- 20356656 TI - Combating oxidative stress in epilepsy: design, synthesis, quantum chemical studies and anticonvulsant evaluation of 1-(substituted benzylidene/ethylidene)-4 (naphthalen-1-yl)semicarbazides. AB - A series of 1-(substituted benzylidene/ethylidene)-4-(naphthalen-1 yl)semicarbazides (3a-19a; 3b-6b) were synthesized in good yield and evaluated for their anticonvulsant and antioxidant activities. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. All of the compounds were found to be active in MES and scPTZ tests. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. Electronic properties were found to be the principal modulator of both anticonvulsant and antioxidant activities. A computational study was carried out for prediction of pharmacokinetic properties and none of the compounds violated Lipinski's rule of 5, making them potentially promising agents for the treatment of epilepsy. PMID- 20356657 TI - Analgesic, anti-pyretic and DNA cleavage studies of novel pyrimidine derivatives of coumarin moiety. AB - A novel series of 4-[4-(6-phenyl-pyrimidin-4-yl)-phenoxymethyl]-chromen-2-ones [5 7(a-e)] were synthesized from various 4-bromomethyl coumarins 1(a-e). The synthesized compounds were screened for in-vivo analgesic and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight (b.w), respectively. Among them, compounds 5(d), 6(c) and 7(d) exhibited significant analgesic activity comparable with standard drug analgin using Tail-flick model. Compounds 5(a) and 7(a-d) showed significant anti-pyretic activities comparable with standard drug aspirin using yeast-induced pyrexia model. DNA cleavage study by agarose gel electrophoresis method was also studied. Qualitative SAR studies indicate that, compounds with amino group at 2-position of pyrimidine ring enhances analgesic and anti-pyretic activities and compounds with hydroxyl and thio group at 2 position of pyrimidine ring increase DNA cleavage activities. PMID- 20356658 TI - Synthesis of novel 6,6a,7,8-tetrahydro-5H-naphtho[1,2-e]pyrimido[4,5 b][1,4]diazepines under microwave irradiation as potential anti-tumor agents. AB - A new series of 6,6a,7,8-tetrahydro-5H-naphtho[1,2-e]pyrimido[4,5 b][1,4]diazepines 4a-f and 5a-f were efficiently synthesized in good yields from the reaction of E-2-arylidene-1-tetralones 1 and the respective tri- or tetraaminopyrimidines 2 or 3 under microwave irradiation using DMF as solvent and catalytic amounts of BF(3).OEt(2). Six of the obtained compounds were selected and tested by the National Cancer Institute (NCI-USA) against 60 different tumor cell lines. In particular, compounds 5a, 5c and 5e presented remarkable anti tumor activity against melanoma cancer in SK-MEL-5 cell line. PMID- 20356659 TI - [Is corticosteroid-induced adrenal insufficiency predictable?]. PMID- 20356660 TI - Detection of antibiotic resistance and tetracycline resistance genes in Enterobacteriaceae isolated from the Pearl rivers in South China. AB - This study investigated antibiotic resistance profiles and tetracycline resistance genes in Enterobacteriaceae family isolates from the Pearl rivers. The Enterobacteriaceae isolates were tested for susceptibility to seven antibiotics ampicillin, chloramphenicol, ciprofloxacin, levofloxacin, sulphamethoxazole/trimethoprim, tetracycline and trimethoprim. In Liuxi reservoir, with an exception to ampicillin resistant strains (11%) no other antibiotic resistance bacterial strains were detected. However, multiple drug resistance in bacterial isolates from the other sites of Pearl rivers was observed which is possibly due to sewage discharge and input from other anthropogenic sources along the rivers. Four tetracycline resistance genes tet A, tet B, tet C and tet D were detected in the isolates from the rivers. The genes tet A and tet B were widely detected with the detection frequencies of 43% and 40% respectively. Ciprofloxacin and levofloxacin resistant enteric bacteria were also isolated from the pig and duck manures which suggest a wider distribution of human specific drugs in the environment. This investigation provided a baseline data on antibiotic resistance profiles and tetracycline resistance genes in the Pearl rivers delta. PMID- 20356661 TI - The protective effects of civic communities against all-cause mortality. AB - This study integrates the civic community framework from sociology into ecological research on mortality rates. The main hypothesis is that communities with high levels of civic engagement, a strong institutional infrastructure for civic participation, and a vibrant entrepreneurial economic climate should have lower rates of all-cause mortality. The analysis drew on data from the CDC WONDER system database for all counties in the US. The results from weighted least squares analysis of county level all-cause mortality rates age-adjusted to the 2000 population provide substantial support for the civic community perspective. Net of a range of important control variables, civically strong communities exhibit significantly lower rates of all-cause mortality. PMID- 20356662 TI - What do physicians gain (and lose) with experience? Qualitative results from a cross-national study of diabetes. AB - An empirical puzzle has emerged over the last several decades of research on variation in clinical decision making involving mixed effects of physician experience. There is some evidence that physicians with greater experience may provide poorer quality care than their less experienced counterparts, as captured by various quality assurance measures. Physician experience is traditionally narrowly defined as years in practice or age, and there is a need for investigation into precisely what happens to physicians as they gain experience, including the reasoning and clinical skills acquired over time and the ways in which physicians consciously implement those skills into their work. In this study, we are concerned with 1) how physicians conceptualize and describe the meaning of their clinical experience, and 2) how they use their experience in clinical practice. To address these questions, we analyzed qualitative data drawn from in-depth interviews with physicians from the United States, United Kingdom, and Germany as a part of a larger factorial experiment of medical decision making for diabetes. Our results show that common measures of physician experience do not fully capture the skills physicians acquire over time or how they implement those skills in their clinical work. We found that what physicians actually gain over time is complex social, behavioral and intuitive wisdom as well as the ability to compare the present day patient against similar past patients. These active cognitive reasoning processes are essential components of a forward looking research agenda in the area of physician experience and decision making. Guideline-based outcome measures, accompanied by underdeveloped age- and years based definitions of experience, may prematurely conclude that more experienced physicians are providing deficient care while overlooking the ways in which they are providing more and better care than their less experienced counterparts. PMID- 20356663 TI - Surgical navigation in correction of hemimandibular hyperplasia: a new treatment strategy. PMID- 20356664 TI - Effects of installation depth on survival of an hydroxyapatite-coated Bicon implant for single-tooth restoration. AB - PURPOSE: The present retrospective study evaluated various implant surface factors associated with Bicon implant survival for single-tooth restoration in the healthy individual. PATIENTS AND METHODS: A retrospective cohort study design was used. A total of 613 Bicon (Bicon System, Boston, MA) implants (272 patients) were included. Because the use of hydroxyapatite (HA) coating has been controversial, the surface type was chosen according to the patient's preference. A total of 308 HA-coated implants and 305 titanium plasma-sprayed (TPS) implants were used. The macroanatomy of both implant types was identical. Patients who had systemic disease, poor quality bone, or removable prosthetics were excluded from the present study. A chart review was conducted to record age, gender, implant diameter, implant length, installation depth, installation location, and the use of bone grafting. Implant failure was recorded, and the data were analyzed using the chi(2) test and logistic regression analysis. RESULTS: The installation depth was an important prognostic factor in the HA-coated implants. The failure rate for the HA-coated implants installed at margin level and 2 mm below level was 10.29% and 3.01%, respectively (chi(2) = 6.035, P = .014). The implant length was an important prognostic factor for the TPS-treated implants. The failure rate recorded for the TPS-treated implants installed with a length of less than 10 mm and 10 mm or longer was 15.46% and 2.40%, respectively (chi(2) = 18.414, P < .001). CONCLUSION: Many factors can influence the failure rate of TPS and HA coated Bicon implants. Among these, installation depth played an especially significant role in the success of HA-coated Bicon implants in the present study. PMID- 20356665 TI - Does computed tomographic assessment of inferior alveolar canal cortical integrity predict nerve exposure during third molar surgery? AB - PURPOSE: To evaluate the association between computed tomographic (CT) assessment of inferior alveolar nerve (IAN) canal cortical integrity and intraoperative IAN exposure. MATERIALS AND METHODS: This was a retrospective cohort study. The study sample included patients considered at high risk for IAN injury based on panoramic findings. The primary predictor variable was IAN canal integrity (intact or interrupted) assessed on coronal CT images. The secondary predictor variable was length of the cortical defect, in millimeters. The primary outcome variable was intraoperative visualization of the IAN. Other variables were demographic and operative parameters. Bivariate and multiple logistic regression analyses were used to evaluate the unadjusted and adjusted associations between the cortical integrity and IAN exposure. Diagnostic test characteristics were computed for cortical integrity and threshold cortical defect size. A P value < or = 0.05 was statistically significant. RESULTS: The sample consisted of 51 subjects (57% female) with a mean age of 35.2 +/- 12.8 years. Of the 80 third molars available for evaluation, 52 third molars (64.1%) had evidence of loss of cortical integrity. The mean cortical defect length was 2.9 +/- 2.6 mm. Loss of cortical integrity had a high sensitivity (> or = 0.88) but low specificity (< or = 0.49) as a diagnostic test for IAN visualization. A cortical defect size > or = 3 mm was associated with an increased risk for intraoperative IAN visualization with a high sensitivity and specificity (> or = 0.82). CONCLUSION: Cortical defect size on a maxillofacial CT has a high sensitivity and specificity for predicting intraoperative IAN exposure during third molar removal. PMID- 20356666 TI - In vitro association of fragments of a beta-sheet membrane protein. AB - Although the beta-barrel membrane protein OmpA can be produced in a biologically active form in E. coli from co-expressed fragments, the fragments have not been demonstrated to associate in vitro. We have produced 3 complementary fragment pairs of OmpA which can associate to form a folded complex according to the SDS band-shift assay. We are able to convert 25-35% of the fragment populations to non-covalent but SDS-stable complexes. The periplasmic chaperone Skp effectively prevented this association. Two separately expressed and purified overlapping fragments of OmpA can form a protease-resistant complex that undergoes the characteristic band-shift upon heating. Our work demonstrates that although membrane insertion and folding of beta-barrel membrane proteins may be a cooperative process, the fragments can associate in vitro without any additional components. However, the low yield and slow folding rates indicate that partially unfolded or destabilized beta-sheet membrane proteins can potentially engage in many non-native interactions. PMID- 20356668 TI - Application of polyacrylamide to reduce phosphorus losses from a Chinese purple soil: a laboratory and field investigation. AB - Use of anionic polyacrylamide (PAM) to control phosphorus (P) losses from a Chinese purple soil was studied in both a laboratory soil column experiment and a field plot experiment on a steep slope (27%). Treatments in the column study were a control, and PAM mixed uniformly into the soil at rates of 0.02, 0.05, 0.08, 0.10, and 0.20%. We found that PAM had an important inhibitory effect on vertical P transport in the soil columns, with the 0.20% PAM treatment having the greatest significant reduction in leachate soluble P concentrations and losses resulting from nine leaching periods. Field experiments were conducted on 5m wide by 21m long natural rainfall plots, that allowed collection of both surface runoff and subsurface drainage water. Wheat was planted and grown on all plots with typical fertilizer applied. Treatments included a control, dry PAM at 3.9 kg ha(-1), dry PAM at 3.9 kg ha(-1) applied together with lime (CaCO(3) at 4.9 t ha(-1)), and dry PAM at 3.9 kg ha(-1) applied together with gypsum (CaSO(4).2H(2)O at 4 t ha( 1)). Results from the field plot experiment in which 5 rainfall events resulted in measurable runoff and leachate showed that all PAM treatments significantly reduced runoff volume and total P losses in surface runoff compared to the control. The PAM treatments also all significantly reduced water volume leached to the tile drain. However, total P losses in the leachate water were not significantly different due to the treatments, perhaps due to the low PAM soil surface application rate and/or high experimental variability. The PAM alone treatment resulted in the greatest wheat growth as indicated by the plant growth indexes of wheat plant height, leaf length, leaf width, grain number per head, and dried grain mass. Growth indexes of the PAM with Calcium treatments were significantly lesser. These results indicate that the selection and use of soil amendments need to be carefully determined based upon the most important management goal at a particular site (runoff/nutrient loss control, enhanced plant growth, or a combination). PMID- 20356669 TI - Urinary incontinence, overactive bladder, and other lower urinary tract symptoms: a longitudinal population-based survey in men aged 45-103 years. AB - BACKGROUND: Lower urinary tract symptoms (LUTS) such as urinary incontinence (UI) and overactive bladder (OAB) are highly prevalent conditions, but there are few studies describing progression and remission of LUTS in men, especially over the long term. OBJECTIVE: To describe the prevalence of UI, OAB, and LUTS using current International Continence Society definitions in the same men studied longitudinally over time. DESIGN: Prospective, population-based, longitudinal study. SETTING AND PARTICIPANTS: In 1992, 10 458 men aged 45-99 yr, resident in the city of Gothenburg, were selected at random from the Population Register. MEASUREMENTS: The men received a postal questionnaire about the presence of LUTS, as well as questions on social, medical, health-related quality of life (HRQoL), and demographic data. Responders in 1992 were reassessed 11 yr later in 2003 using a similar questionnaire. RESULTS AND LIMITATIONS: In 2003, 4072 of the 7763 men who responded in 1992 were still available in the Population Register and 3257 men (80%) aged 56-103 yr, responded. Prevalence of UI and OAB had increased (p<0.01) in the same men assessed in 1992 (4.5% and 15.6%, respectively) and 2003 (10.5% and 44.4%, respectively). The prevalence of nocturia, urgency, slow stream, hesitancy, incomplete emptying, postmicturition dribble, and the number of daytime micturitions had also increased (p<0.01). Only a minority reported regression of symptoms. Men with UI or OAB reported a poorer (p<0.001) HRQoL compared with men without UI or OAB. CONCLUSIONS: There was a marked increase in the prevalence of UI, OAB, and other LUTS in the same men assessed longitudinally over this 11-yr period. UI and OAB had a negative influence on HRQoL, and men who developed UI or OAB had a greater deterioration in HRQoL than men who had no change in their UI/OAB status over time. PMID- 20356667 TI - Differentiation and mineralization of murine mesenchymal C3H10T1/2 cells in micromass culture. AB - The murine mesenchymal cell line, C3H10T1/2 in micromass culture undergoes chondrogenic differentiation with the addition of BMP-2. This study compares the use of BMP-2 vs. insulin, transferrin, and sodium selenite (ITS) to create a chondrogenic micromass cell culture system that models cartilage calcification in the presence of 4mM inorganic phosphate. BMP-2 treated cultures showed more intense alcian blue staining for proteoglycans than ITS treated cultures at early time points. Both ITS and BMP-2 treated cultures showed similar mineral deposition in cultures treated with 4mM phosphate via von Kossa staining, however FTIR spectroscopy of cultures showed different matrix properties. ITS treated cultures produced matrix that more closely resembled mouse calcified cartilage by FTIR analysis. (45)Ca uptake curves showed delayed onset of mineralization in cultures treated with BMP-2, however they had an increased rate of mineralization (initial slope of (45)Ca uptake curve) when compared to the cultures treated with ITS. Immunohistochemistry showed the presence of both collagens type I and type II in BMP-2 and ITS treated control (1mM inorganic phosphate) and mineralizing cultures. BMP-2 treated mineralizing cultures displayed more intense staining for collagen type II than all other cultures. Collagen type X staining was detected at Day 9 only in mineralizing cultures treated with ITS. Western blotting of Day 9 cultures confirmed the presence of collagen type X in the mineralizing ITS cultures, and also showed very small amounts of collagen type X in BMP-2 treated cultures and control ITS cultures. By Day 16 all cultures stained positive for collagen type X. These data suggest that BMP-2 induces a more chondrogenic phenotype, while ITS treatment favors maturation and hypertrophy of the chondrocytes in the murine micromass cultures. PMID- 20356671 TI - Cloning and characterization of a new BRCA1 variant: A role for BRCT domains in apoptosis. AB - BRCA1 is a tumor-suppressor gene responsible for hereditary breast and ovarian cancers. Characterization of alternately spliced forms of BRCA1 may identify the region of the gene responsible for its function. Here, we cloned and characterized a new BRCA1 splicing variant from the breast cancer cell line ZR-75 30. This transcript, named BRCA1-E1aA-Delta2-17, lacks most exons found in full length BRCA1, but maintains the original reading frame. We detected expression of the BRCA1-E1aA-Delta2-17 transcript in several human cell lines and tumor tissues, and the fusion protein GFP-BRCA1-E1aA-Delta2-17 localized to the nucleus. Likewise, overexpression of the BRCA1-E1aA-Delta2-17 transcript resulted in cell death as measured by the MTT assay, and fluorescence activated cell sorting (FACS) assays confirmed that this was caused by cellular apoptosis. Our data imply that BRCT domains of the BRCA1 play a role in the cellular apoptosis we observed, and suggest that elucidating the specific function of each of the domains could aid in understanding the exact role of the BRCA1 tumor suppressor. PMID- 20356670 TI - Compensatory activation of Akt in response to mTOR and Raf inhibitors - a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease. AB - Several studies have established a link between aberrant PI(3)K-Akt-mTOR- and Ras Raf-MEK-Erk1/2 signaling and neuroendocrine tumor disease. In this study, we comparatively investigate the antitumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antitumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K-Akt-mTOR- and Ras-Raf MEK-Erk1/2 signaling in NET disease. PMID- 20356672 TI - Heavy metal removal from municipal solid waste fly ash by chlorination and thermal treatment. AB - Municipal solid waste (MSW) fly ash is classified as a hazardous material because it contains high amounts of heavy metals. For decontamination, MSW fly ash is first mixed with alkali or alkaline earth metal chlorides (e.g. calcium chloride) and water, and then the mixture is pelletized and treated in a rotary reactor at about 1000 degrees C. Volatile heavy metal compounds are formed and evaporate. In this paper, the effect of calcium chloride addition, gas velocity, temperature and residence time on the separation of heavy metals are studied. The fly ash was sampled at the waste-to-energy plant Fernwarme Wien/Spittelau (Vienna, Austria). The results were obtained from batch tests performed in an indirectly heated laboratory-scale rotary reactor. More than 90% of Cd and Pb and about 60% of Cu and 80% of Zn could be removed in the experiments. PMID- 20356673 TI - Thermodynamic modelling of the formation of zinc-manganese ferrite spinel in electric arc furnace dust. AB - Electric arc furnace dust is generated when automobile scrap, containing galvanized steel, is remelted in an electric arc furnace. This dust is considered as a hazardous waste in most countries. Zinc is a major component of the dust and can be of significant commercial value. Typically, the majority of the zinc exists as zinc oxide (ZnO) and as a zinc-manganese ferrite spinel ((Zn(x)Mn(y)Fe(1-x-y))Fe(2)O(4)). The recovery of the zinc from the dust in metal recycling and recovery processes, particularly in the hydrometallurgical extraction processes, is often hindered by the presence of the mixed ferrite spinel. However, there is a paucity of information available in the literature on the formation of this spinel. Therefore, in the present research, the equilibrium module of HSC Chemistry 6.1 was utilized to investigate the thermodynamics of the formation of the spinel and the effect of variables on the amount and the composition of the mixed ferrite spinel. It is proposed that the mixed ferrite spinel forms due to the reaction of iron-manganese particulates with both gaseous oxygen and zinc, at the high temperatures in the freeboard of the furnace above the steel melt. Based on the thermodynamic predictions, methods are proposed for minimizing the formation of the mixed ferrite spinel. PMID- 20356674 TI - Adsorption of Pb(II) ions from aqueous solution by native and activated bentonite: kinetic, equilibrium and thermodynamic study. AB - In this study, the adsorption kinetics, equilibrium and thermodynamics of Pb(II) ions on native (NB) and acid activated (AAB) bentonites were examined. The specific surface areas, pore size and pore-size distributions of the samples were fully characterized. The adsorption efficiency of Pb(II) onto the NB and AAB was increased with increasing temperature. The kinetics of adsorption of Pb(II) ions was discussed using three kinetic models, the pseudo-first-order, the pseudo second-order and the intra-particle diffusion model. The experimental data fitted very well the pseudo-second-order kinetic model. The initial sorption rate and the activation energy were also calculated. The activation energy of the sorption was calculated as 16.51 and 13.66 kJ mol(-1) for NB and AAB, respectively. Experimental results were also analysed by the Langmuir, Freundlich and Dubinin Redushkevich (D-R) isotherm equations at different temperatures. R(L) separation factor for Langmuir and the n value for Freundlich isotherm show that Pb(II) ions are favorably adsorbed by NB and AAB. Thermodynamic quantities such as Gibbs free energy (DeltaG), the enthalpy (DeltaH) and the entropy change of sorption (DeltaS) were determined as about -5.06, 10.29 and 0.017 kJ mol(-1) K(-1), respectively for AAB. It was shown that the sorption processes were an endothermic reactions, controlled by physical mechanisms and spontaneously. PMID- 20356675 TI - Alteration of cortical excitability in patients with fibromyalgia. AB - We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia. PMID- 20356676 TI - Capsicum and local anesthetic cocktails for trigeminal pain. PMID- 20356677 TI - Atomic scale investigation on the distribution of boron in medium carbon steels by atom probe tomography and EELS. AB - The medium carbon (0.5 wt% C) steels containing various boron contents were studied to observe the distribution of boron using atom probe tomography and electron energy loss spectroscopy. APT revealed the segregation of boron atoms at retained austenite for 100 ppm boron added steels and the trapped carbon atoms at micro-twins for 50 ppm boron treated steels. Moreover, it was also found that boron was randomly distributed for 20 ppm boron added steels regardless of the interactions between carbon and boron. PMID- 20356679 TI - Anthelmintic efficacy and management practices in sheep farms from the state of Rio de Janeiro, Brazil. AB - Anthelmintic resistance in parasites maybe a consequence of over-exposing populations of parasites to drugs or from the commerce/transit of animals harboring resistant parasites. Knowledge of the sensitivity of nematodes to anthelmintics is essential to establish an efficient integrated program of parasite control. In Brazil, producers rely on technology transfer from field professionals and non-technical labor for new management strategies of parasite control. The aim of this work was to determine the practices farmers used for anthelmintic management and to monitor drug efficacy on sheep farms from northern and northwestern regions of the state of Rio de Janeiro, Brazil. A questionnaire was sent to 34 farms, and anthelmintics were tested on ten of these farms. Sheep (n=10/group) were weighed and treated with albendazole, closantel, doramectin, fenbendazole, ivermectin, levamisole, moxidectin, or nitroxynil with their recommended doses. Faeces were collected on the day of treatment and after 7-10 days. The faecal egg count reduction test was evaluated based on RESO 2.0. Among the farmers interviewed, 97% applied commercial anthelmintics to control parasites, 77% rotated anthelmintics annually, 72% used ivermectin as the principal anthelmintic, and 38% applied anthelmintics with a frequency of 30-60 days. On two farms, none of the anthelmintics was efficacious. Levamisole had the best overall efficacy (70%). Albendazole, ivermectin, and fenbendazole were efficacious (above 95%) on only two farms. The present work illustrates the alarming lack of efficacy of drugs even in an area new to sheep farming. It is important to establish alternative strategies of management in a broad program of parasite control for reducing the selection pressure on parasites by the commercially available anthelmintics. PMID- 20356678 TI - Molecular characterization and assessment of zoonotic transmission of Cryptosporidium from dairy cattle in West Bengal, India. AB - Few studies in the past have examined the genetic diversity and zoonotic potential of Cryptosporidium in dairy cattle in India. To assess the importance of these animals as a source of human Cryptosporidium infections, fecal samples from 180 calves, heifers and adults and 51 farm workers on two dairy farms in West Bengal, India were genotyped by PCR-RFLP analysis of the 18S rRNA gene of Cryptosporidium followed by DNA sequencing of the PCR products. Phylogenetic analysis was carried out on the DNA sequences obtained in the study and those available in GenBank. The overall prevalence of Cryptosporidium in cattle was 11.7% though the infection was more prevalent in younger calves than in adult cattle. The occurrence of Cryptosporidium parvum, Cryptosporidium bovis, Cryptosporidium ryanae and Cryptosporidium andersoni in cattle followed an age related pattern. A Cryptosporidium suis-like genotype was also detected in a calf. Farm workers were infected with Cryptosporidium hominis, C. parvum and a novel C. bovis genotype. These findings clearly suggest that there is a potential risk of zoonotic transmission of Cryptosporidium infections between cattle and humans on dairy farms in India. PMID- 20356680 TI - Selective anthelmintic therapy of horses in the Federal states of Bavaria (Germany) and Salzburg (Austria): an investigation into strongyle egg shedding consistency. AB - For 9 consecutive months (March-November 2008), faecal samples were collected monthly from 129 horses residing within 40 km of Salzburg, Austria. Samples were analysed quantitatively using a modified McMaster egg counting technique. Whenever a faecal egg count (FEC) result exceeded 250 eggs per gram (EPG), the horse was treated with pyrantel, ivermectin or moxidectin. In 52 of 129 horses (40.3%), no strongyle eggs were ever detected over the course of 9 months. In 39 horses (30.2%), strongyle eggs were detected in at least 1 sample, but the egg count never exceeded 250 EPG. The remaining 38 (29.5%) horses were treated at least once in response to a FEC that exceeded 250 EPG. As a result of this selective anthelmintic scheme, the total number of anthelmintic treatments was reduced to 54% of the number of treatments administered to the same horses in the previous year. Both the maximum and mean FEC dropped significantly after initiation of the study. A statistically significant, negative correlation was demonstrated between the maximum and mean FEC of a horse and its age. Pasture hygiene appeared to reduce FECs, but the effect was not statistically significant. The magnitude of the initial FEC was significantly correlated with the maximum FECs in the subsequent 8 months (p<0.01). The same relationship was observed for the maximum FEC of the first 2 samples. Furthermore, horses which required several anthelmintic treatments had a higher initial FEC and a greater maximum FEC in the first 2 samples than horses which received only one or no treatment. These results suggest that selective anthelmintic treatment accomplished a reduced pasture contamination with strongyle eggs, while simultaneously decreasing the number of anthelmintic treatments. Sustained implementation of a selective treatment strategy has the potential to reduce selection pressure for anthelmintic resistance. These results reported herein will assist equine practitioners in designing and monitoring sustainable anthelmintic treatment programs. PMID- 20356682 TI - Development of the Stimulant Medication Outcome Expectancies Questionnaire for college students. AB - Non-prescribed use of stimulant medication among college students has become a public health concern. Although it has been well-established that outcome expectancies play a prominent role in initiation and maintenance of drinking behaviors it is unknown if and how outcome expectancies influence non-prescribed use of stimulant medication among college students. The aim of this study was to develop a valid and reliable scale that assesses outcome expectancies of non prescribed use of stimulant medication. A 16-item Stimulant Medication Outcome Expectancy Questionnaire (SMOEQ) was created using qualitative information given by introductory psychology students regarding their expectancies about misusing stimulant medication. An exploratory factor analysis (EFA) identified a three factor solution: the Academic factor, Recreational factor, and Negative Physiological Effects factor, respectively. A confirmatory factor analysis (CFA) validated the factor structure identified in the EFA and indicated a modest fit of the hypothesized factor structure to the data. Correlation analyses provided support for the internal consistency and construct validity of the SMOEQ. PMID- 20356681 TI - Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding. AB - BACKGROUND: Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5 HT(2A)) receptor binding in men. METHODS: In a group of 72 healthy men (mean age 37.5 years +/-17.4 SD, range 19.6-81.7) we studied the effect of plasma sex hormone levels on neocortical 5-HT(2A) receptor binding as imaged with [(18)F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. RESULTS: Mean neocortical 5-HT(2A) receptor binding was positively correlated with estradiol (p=0.0001), whereas no independent effects of testosterone could be demonstrated. Correction for other factors of importance for 5-HT(2A) receptor binding did not change the result. A voxel-based analysis suggested that there were no regional differences in the estradiol effect on cortical 5-HT(2A) receptor binding. CONCLUSIONS: Our data show a positive correlation between endogenous plasma estradiol levels and cortical 5-HT(2A) receptor binding in healthy men, whereas, no independent effect of testosterone was demonstrated. We speculate that this association could be mediated through effects on gene transcription. PMID- 20356683 TI - Development of a short cannabis problems questionnaire for adolescents in the community. AB - The widespread and harmful use of cannabis amongst young people in the community has been well established. In order to assist in identifying young people at risk of harm for their cannabis use, the present paper documents the development of a short 12-item cannabis problems measure--the Cannabis Problems Questionnaire for Adolescents, Short form (CPQ-A-S). The CPQ-A-S was derived from the 27-item Cannabis Problems Questionnaire for Adolescents (CPQ-A) which had been shown in an earlier study to be a reliable and valid indicator of cannabis problems in adolescents. Tetrachoric correlations amongst items were examined and the more redundant items removed. Psychometrics of the shorter scale were then evaluated through factor analysis, and logistic regression used to demonstrate scale validity. This is the first short scale of cannabis problems derived for adolescents and it should prove a useful tool in both research and community applications. PMID- 20356684 TI - DNA--a molecule in search of additional functions: recipient of pool wave emissions? A hypothesis. AB - Almost the entire nucleotide sequence of human DNA is functionally unaccounted for, although large parts of the human genome are transcribed. The genes, as defined by current molecular biology, comprise about 1.5-2% of the DNA molecule. It is proposed that DNA encodes additional, hitherto unrecognized functions. In this discussion, the total information inside and outside the universe we live in is termed the pool or the sum total, known or unknown, of all laws, matter, energy, concepts and events. In a hypothetical model, a Gedankenexperiment, it is suggested that the total of all information emits pool waves of an unknown physical nature. They could be related to black energy or have completely different qualities. The designation pool waves should not imply any similarity to electromagnetism. Further, DNA is suggested to have the capability of interacting with the pool waves and thus permit humans - to some partly genetically determined and yet very limited extent - to perceive information from the pool. Pool emissions might be one of the forces that have been instrumental in and are still driving evolution from simple oligonucleotides to DNA with ever more complex recipient capacities. It will be a major challenge for researchers in the field to unravel these and less hypothetical undetected coding principles in DNA. It is uncertain whether the current trend to search the available DNA sequences with ever more refined computer technology on the basis of our present understanding of biology will detect unknown coding systems. For molecular medicine, research into the genetics of the most common human diseases could profit from the elucidation of presently still ephemeral codes in human DNA. Young scientists with a proven record of original research deserve support for the pursuit of unconventional ideas. This concept of granting priorities will be of the utmost importance in advancing the field beyond current concepts in molecular biology. PMID- 20356685 TI - Pathological research output in China and other top-ranking countries: 10-year survey of the literature. AB - The present study was designed to study the research output in pathology journals from the United States (USA), Japan, Germany, the United Kingdom (UK), France, and China between 2000 and 2009. Articles published in 67 pathology-related journals were retrieved from the PubMed database. US-American publications, which rank first, accounted for 30.9% of the total world's output and for 35.4% in the top 10% journals with impact factor (IF) scores. Chinese publications accounted for 2.8% of a total of 67 journals, and for 2.0% in the top 10% journals with IF scores. Our analysis investigated the research output of these six countries and revealed a positive trend in China for the period 2000-2009. Also, in contrast to other top-ranking countries, our results imply that China's research in the field of pathology falls behind that of the developed countries, and appropriate steps should be taken to improve the role of pathologists in clinical activity and to gear up for high-quality pathological studies. PMID- 20356686 TI - Melanotic schwannoma: a case with strong CD34 expression, with histogenetic implications. AB - Melanotic schwannomas (MS) are rare tumors composed of cells with both schwannian and melanocytic features, which usually occur in the setting of Carney's Complex. We describe a case of a 36-year-old male who presented with a mass that was attached to the vertebral body as well as the nerve roots of L2 and L3. Immunohistochemical positivity for S-100, HMB-45, and Pan-melanoma markers, as well as characteristic morphologic and ultrastructural findings, suggested that the lesion was a MS. The interest in this case lies in the fact that this case of MS showed strong CD34 expression, a marker that is generally negative in melanocytic tumors. We discuss the biologic significance of the high CD34 expression by the tumor cells and attempt to shed light on the histogenesis of this rare entity. PMID- 20356687 TI - Timing of salvage hormonal therapy in prostate cancer patients with unfavorable prognosis treated with radiotherapy: a secondary analysis of Radiation Therapy Oncology Group 85-31. AB - PURPOSE: Radiation Therapy Oncology Group 85-31 was a randomized trial comparing radiotherapy (RT) alone vs. RT plus adjuvant androgen suppression for life in unfavorable-prognosis carcinoma of the prostate. We examined the impact of early initiation of salvage hormonal therapy (HT) in relapsing patients randomized to RT alone arm. METHODS AND MATERIALS: Patients were divided into two groups: early salvage HT and late salvage HT. The early salvage group was defined as receiving HT with a prostate-specific antigen (PSA) level of less than 10 ng/mL, and the late salvage HT group had a PSA level of 10 ng/mL or greater. The outcomes were overall survival (OS), cause-specific mortality (CSM), and local failure (LF). The Kaplan-Meier estimation and log-rank test were used for OS, and the cumulative incidence estimation and Gray's test were used for CSM and LF. Proportional hazards regression models were used to compare the outcomes adjusted for other covariates. RESULTS: The median follow-up times of surviving patients in the early and late salvage HT groups were about 11 and 13 years, respectively. The late salvage HT group had significantly more post-prostatectomy patients and patients with high Gleason scores. After adjustment for all covariates, OS was significantly longer in the early salvage HT group (hazard ratio, 1.5; p = 0.01). However, there were no statistically significant differences in LF or CSM between the groups. CONCLUSIONS: The early introduction of salvage HT resulted in improved OS but not improved CSM and LF. A randomized trial to define the optimal salvage hormonal timing is warranted in this group of patients with PSA recurrence after RT. PMID- 20356688 TI - [Recurrent spontaneous miscarriage: etiology, and management of subsequent pregnancies]. PMID- 20356689 TI - [About the very first obstetrical printed books in French language]. PMID- 20356690 TI - Aerobic exercise during pregnancy influences fetal cardiac autonomic control of heart rate and heart rate variability. AB - BACKGROUND: Previous studies using ultrasound technology showed that fetal heart rate (HR) may be responsive to maternal aerobic exercise. Although it is recognized that cardiac autonomic control may be influenced by the intrauterine environment, little is known about how maternal exercise affects fetal heart development. AIMS: This study tested the hypothesis that regular maternal exercise throughout gestation influences fetal cardiac autonomic control of HR and heart rate variability (HRV) when compared to fetuses of non-exercising women. STUDY DESIGN: Magnetocardiograms (MCGs) were recorded using a dedicated fetal biomagnetometer at 28, 32 and 36 weeks gestational age (GA) from 26 regularly exercising (>30 min of aerobic exercise, 3x per week) and 35 healthy, non-exercising pregnant women. Fetal MCG was isolated and normal R-peaks were marked to derive fetal HR and HRV in the time and frequency domains. We applied a mixed-effects model to investigate the effects of exercise, GA and fetal activity state. RESULTS: At 36 weeks GA, during the active fetal state, fetal HR was significantly lower in the exercise group (p=<0.0006). Post-hoc comparisons showed significantly increased HRV in the exercise group during the active fetal state at 36 weeks GA for both time and frequency domain measures. CONCLUSION: These results indicate that regular maternal exercise throughout gestation results in significantly lower fetal HR and increased HRV. PMID- 20356691 TI - One size may not fit all: pondering antibiotic dosing in obesity. PMID- 20356692 TI - Should bisphosphonates be used in premenopausal women? PMID- 20356693 TI - Sudden death due to spontaneous rupture in splenic artery atypical dissection with features of vasculitis: case report and review of the literature. AB - A case of sudden death in a 45-year-old man due to splenic artery dissection and rupture diagnosed at a medico-legal autopsy is described. The examination of the splenic artery revealed macroscopically the features of a ruptured intramural haematoma (no intimal tear, no lumen dilation) and histologically the characteristics of a lymphoplasmacytic vasculitis of the vasa vasorum associated with fibrinoid degeneration. The patient died at home after having been discharged from hospital where he had presented for modest abdominal pain with no evidence of the true nature of the disease found using echography. The Authors discuss the literature relative to splenic artery dissection (13 cases of which only one diagnosed in vivo), the present case being the only one due to vasculitis of the vasa vasorum and the forensic implications (autopsy was ordered to examine the causes of death, to verify whether diagnosis could have been reached during hospitalization with consequences on the outcome and if a hypothesis of malpractice could be prospected). PMID- 20356694 TI - Migraine in school children. PMID- 20356695 TI - D225G mutation in the hemagglutinin protein found in 3 severe cases of 2009 pandemic influenza A (H1N1) in Spain. AB - From 27 April to 16 December 2009, we analyzed the hemagglutinin gene sequence of 2009 pandemic influenza A (H1N1) virus in 189 respiratory specimens. We only found the D225G mutation in 3 severe cases. However, it was not found in samples from other cases with or without clinical criteria of severity. The biologic significance of this mutation remains still unclear. PMID- 20356696 TI - Hydrophobic fractions from Strongyloides venezuelensis for use in the human immunodiagnosis of strongyloidiasis. AB - The objective of the present research was to evaluate detergent and aqueous phases of total saline (TS) and alkaline extracts of Strongyloides venezuelensis for human strongyloidiasis immunodiagnosis. Total extracts and detergent and aqueous antigenic fractions were separated using Triton X-114 and were examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB) tests to detect immunoglobulin G (IgG). Serum samples were obtained from 120 individuals: 40 strongyloidiasis patients (group I), 40 patients with other parasitic diseases (group II), and 40 apparently healthy individuals (group III). Each extract provided a different profile of antigenic components as recognized by IgG in IB. The detergent fraction of the TS extract demonstrated the highest sensitivity and specificity for ELISA and IB. The results indicated that the detergent saline fraction, purified from S. venezuelensis, furnished the most valid results for the strongyloidiasis immunodiagnosis and could be employed as an alternative antigen and as a useful source of specific polypeptides. PMID- 20356697 TI - Design and validation of a multiplex polymerase chain reaction for the identification of enterotoxigenic Escherichia coli and associated colonization factor antigens. AB - Development of a genetic tool for the detection of genes encoding enterotoxins and colonization factors would greatly enhance enterotoxigenic Escherichia coli (ETEC) surveillance. Oligonucleotide primers were designed to amplify genes encoding human ST, porcine ST, LT and the structural genes of colonization factor antigen (CFA)/I, CS1 to CS8, CS12 to CS15, CS17 to CS22, and PCFO71. Screening 89 ETEC isolates phenotypically expressing a known CFA showed that, without exception, the multiplex polymerase chain reaction (mPCR) detected the structural gene of the expressed CFA, in addition to CS21 in 22.5% of isolates. Silent genes such as cssB (CS6) were also detected in 9.0%. Additionally, we screened 71 CFA phenotypically negative isolates and detected a CFA in more than 50% of tested isolates. In conclusion, we have designed a simple 4-step mPCR for the rapid detection of ETEC virulence factors. The assay is rapid, reproducible, relatively inexpensive, and has the potential to be field applicable. PMID- 20356698 TI - Susceptibility of Burkholderia pseudomallei to tigecycline and other antimicrobials. PMID- 20356699 TI - Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes. AB - We undertook a retrospective cohort study describing general outcomes and specific factors associated with positive outcomes in bacteremia due to carbapenem-resistant Klebsiella pneumoniae (CRKP). Forty-eight patients were included, of which 42% died at 30 days. Forty-two percent of patients were in septic shock at the time of the first positive blood culture, and 42% were recipients of solid organ transplants. Lack of microbiologic eradication at 7 days was independently associated with 30-day mortality. Adjunctive procedures performed for source control and microbiologic eradication at 7 days were associated with a favorable clinical response at 7 days. Time to initiation and receipt at any time of antimicrobials with in vitro activity against CRKP were not associated with improved survival. Breakthrough bacteremia occurred in 8 cases, all in patients receiving tigecycline. Our data suggest that severity of illness, rapid microbiologic eradication, and source control are crucial factors in the outcomes of patients with CRKP bacteremia. PMID- 20356700 TI - Self-efficacy as a predictor of improvement in health status and overall quality of life in pulmonary rehabilitation--an exploratory study. AB - OBJECTIVE: To evaluate developments in health status (HS) and overall quality of life (QOL), and the impact of self-efficacy on HS and QOL in relation to COPD pulmonary rehabilitation (PR). METHODS: A longitudinal study of 100 COPD patients before and up to 3 months after COPD PR. Self-efficacy was measured by the COPD self-efficacy scale, HS by the St. George Respiratory Questionnaire and QOL by the Quality of Life Scale. Mixed effect models were used. RESULTS: Patients reported significantly reduced psychosocial impact of disease (estimate=-4.05, p=0.019) immediately after the PR programme. Higher levels of self-efficacy at baseline predicted significantly reduced psychosocial impact of disease and improved physical activity, total HS and QOL (p<0.05). Better exercise capacity at baseline predicted significantly reduced psychosocial impact of disease, improved physical activity and QOL (p<0.05). Older age at baseline predicted significantly fewer respiratory symptoms and improved total HS (p<0.05). CONCLUSIONS: Patients reported significantly reduced psychosocial impact of disease immediately after a COPD PR, and better exercise capacity and higher self efficacy at baseline predicted significantly improved HS and QOL. PRACTICE IMPLICATIONS: Increasing self-efficacy is suggested to be an important aim in relation to COPD PR. PMID- 20356701 TI - An invisible power. PMID- 20356702 TI - Assessing criminal justice involvement as an indicator of human immunodeficiency virus risk among women in methadone treatment. AB - This study examines the relationship between criminal justice involvement and high-risk sexual partnerships among a random sample of 416 women in methadone treatment in New York City. Logistic regression models were used to estimate the associations between recent criminal justice involvement (arrest or incarceration in the past 6 months) and recent high-risk partnerships (multiple sex partners, sex trading, or sex with a risky partner in the past 6 months) when adjusting for sociodemographic factors and recent regular drug use. Women with recent criminal justice involvement demonstrated higher odds of engaging in high-risk sex partnerships. Although regular drug use was a significant confounder of several of these relationships, recent arrest or incarceration remained significantly associated with multiple sex partnerships, sex with a risky partner, and engaging in unprotected sex and a high-risk partnership even after controlling for regular drug use and other social stressors. This study highlights the vulnerability of drug-involved women offenders to human immunodeficiency virus (HIV) risk and points to the need for investigation into the role of arrest and incarceration as factors that may contribute to HIV infection. PMID- 20356703 TI - Management of early (<30 day) vascular groin infections using vacuum-assisted closure alone without muscle flap coverage in a consecutive patient series. AB - OBJECTIVE: Vacuum-assisted closure (VAC) therapy without muscle flap coverage is our primary approach for graft preservation in early, deep groin infections with and without exposed grafts; however, concerns exist regarding its safety. We report our experience in a consecutive series of patients with early groin infections managed without muscle flap closure. METHODS: All patients with early (<30 day), deep vascular groin infections without (Szilagyi II) or with (Szilagyi III) exposed vascular graft or suture line between January 2004 and December 2008 were reviewed. Graft preservation followed by local wound care with VAC was attempted in all with intact anastomoses, patent grafts, and absence of systemic sepsis. Szilagyi classification, microorganism cultured, duration of VAC use, time to healing, additional interventions, and follow-up data (limb salvage, survival) were analyzed. RESULTS: Twenty-two patients (26 groins, mean age 69.1 +/- 9.5 years [range, 44-86 years]) presented with deep groin infections 16 +/- 5 days (range, 7-28 days) after the index procedure (bypass-polytetrafluoroethylene [n = 11], autologous vein [n = 3], endarterectomy/patch [n = 6], extra-anatomic bypass [n = 5], percutaneous closure device [n = 1]). Grafts were exposed in 12 groins (Szilagyi III, nine with suture lines). VAC was started one to six days (median, three) after operative debridement. All had positive wound cultures and received culture-directed antibiotic therapy for 47 +/- 45 days (range, 14-180 days). Length of stay was significantly more in Szilagyi III, whereas mean VAC use and time-to-healing were similar. Mean follow-up was 33.4 +/- 19.5 months (range, 2-72 months). All wounds healed (mean, 49 +/- 21 days). Two treatment failures occurred in the Szilagyi III group (17%). One patient had bleeding from the anastomotic heel eight days after debridement, had graft removal/in situ replacement and one presented with reinfection on day 117 and had partial graft removal/extra-anatomic bypass. There was no perioperative mortality or limb loss, but six late unrelated mortalities and one amputation at 46 months unrelated to the groin infection. CONCLUSIONS: Management of early, deep groin wound infections with debridement, antibiotics, and VAC treatment is safe and enables graft preservation in the majority of patients with minimal morbidity, no perioperative limb loss, or mortality. PMID- 20356704 TI - [Kidney and preeclampsia]. AB - During normal pregnancy, renal blood flow and GFR increase gradually until they reach a peak of about 150% of their normal values by the end of the 1(st) trimester. This increase in GFR is secondary to the extra-cellular compartment expansion caused by a positive sodium balance of about 500-900 mmol which is in turn associated with a water retention amounting 6 to 8 liters. Blood pressure decreases during a normal pregnancy because of the decrease in peripheral vascular resistance. This drop in blood pressure is limited by the renin angiotensin system. Blood pressure gradually recovers during the 3(rd) trimester. Systemic hypertension, proteinuria >0.3 g/day and edema are the usual signs leading to the diagnosis of PE. However, any of the above listed signs found in isolation can be a tell tale sign of PE and must therefore prompt for the identification of a possible fetal effect The differential diagnosis of PE includes essential hypertension and hypertension secondary to a pre-existing renal failure. In the latter, signs of renal impairment early in the pregnancy, or (and) renal failure prior to the pregnancy are of important diagnostic clues. Causes of acute renal failure during pregnancy are numerous. PE associated acute renal failure presents in 5-10% of severe forms of PE. This is always a bad prognostic sign with a predicted mortality of 10%. Histological features are those of acute tubular necrosis with "endotheliosis" an inflammation of the glomerular endothelium. This renal impairment is frequently complicated by pulmonary edema. Passed the acute phase, the recovery of the renal function is usually complete. An acute renal failure during pregnancy can also be secondary to a pre-existing renal impairment suddenly aggravated by PE. In this setting, the probability of these patients requiring long term dialysis is high. Post partum Haemolytic-Uremic Syndrome (HUS), although rare, is a serious condition which, following delivery, will require an early diagnosis (haemolysis, hypertension, acute renal failure) and urgently require symptomatic, perhaps specific, treatment (Plasma exchange transfusion). PMID- 20356705 TI - [Prehospital management of severe preeclampsia]. AB - Prior to transport, agreement must be reached among all the senior medical staff members involved in the transfer. Tight clinical surveillance is necessary during the transport. The aim of the pharmacological control of a severe hypertension is to allow a moderate reduction of the mean arterial blood pressure as well as dampening the large pressure variations. Boluses of calcium channel inhibitors, eventually combined with labetalol, are to be used as first line treatment. Systematic fluid expansion prior to admission is not recommended. However, it is indicated if obvious signs of hypovolaemia are present, such as a sudden drop in blood pressure, secondary to the initiating of an antihypertensive therapy. It is possible to use i.v. benzodiazepines for the treatment of eclampsia in the prehospital setting. If magnesium sulfate therapy has been initiated in a preeclamptic woman with neurological signs, it may be continued during her transport. PMID- 20356706 TI - [Fatal varicella: atypical presentation and stabbing outcome]. PMID- 20356707 TI - [Intrahospital management of women with preeclampsia]. AB - The management of the PE patient requires admission in order to perform a meticulous assessment of the mothers' and fetal state, distinguishing between the severe and the mild forms. In moderate forms, the pregnancy is allowed to reach the 37(th) week of gestation. In severe forms of PE, the pregnancy is only allowed to continue under stringent monitoring. Before the 34(th) week of amenorrhea is reached, corticosteroid therapy and transfer to an adapted maternity are recommended. The true benefit provided by antihypertensive therapy in the moderate forms of PE is very limited. The presently recommended antihypertensive agent is nicardipine, which can be used in association with magnesium sulphate provided there is appropriate monitoring. PMID- 20356708 TI - [Low monocytic HLA-DR expression and risk of secondary infection]. AB - OBJECTIVES: The aim of this bibliographic review is to evaluate the usefulness of the measurement of HLA-DR expression on circulating monocytes (mHLA-DR) in predicting the development of nosocomial infections and unfavourable outcome in critically ill patients. DATA SOURCE: References obtained from the medical database PubMed in English and in French were reviewed. The keywords included separately or in combination were: HLA-DR antigens, sepsis, trauma, injuries, wounds, burns, stroke, pancreatitis, postoperative, prognostic, immunity, monocytic. DATA EXTRACTION: Data in selected articles were reviewed, clinical and basic science research relevant information were extracted. DATA SYNTHESIS: Low mHLA-DR expression appears as a marker for monocytic dysfunctions and immunosuppression, temporarily present in the majority of critically ill patients admitted to the ICU (sepsis, trauma injuries, postoperative, burns, pancreatitis and stroke). The decrease in mHLA-DR expression is a predictor of septic complications in all these clinical conditions. However, no predictive threshold value could be determined regarding unfavourable outcome. CONCLUSION: The monitoring of mHLA-DR expression could be a biomarker to detect ICU patients at high risk of developing secondary nosocomial infections. Those patients could probably benefit of preemptive strategies to prevent these infections. PMID- 20356709 TI - Differences in patients with systemic sclerosis recruited from associations and tertiary care settings. AB - OBJECTIVE: To compare patients with systemic sclerosis (SSc) recruited from a patient association or a tertiary care setting. METHODS: We evaluated 248 SSc patients attending 4 annual meetings of a patient association between 2004 and 2007 (177) or during hospitalization (71). health-related quality of life (HRQoL) was assessed by the SF-36, global disability by the health assessment questionnaire (HAQ), hand disability by the Cochin Hand Function Scale (CHFS), mouth disability by the Mouth Handicap in Systemic Sclerosis (MHISS) scale, global hand and wrist mobility by the Kapandji index. RESULTS: As compared with hospitalized patients, those from the patient association were significantly older (mean age 58.73 +/- 12.04 vs 53.818 +/- 13.1; p=0.001) and had a longer disease duration (10.98 +/- 8.7 vs 7.13 +/- 6.723 p=0.0001). Association patients had significantly increased disability of the hand (CHFS 21.8 +/- 19.8 vs 9.8 +/- 14.1; p=0.0001) and mouth (MHISS 20.65 +/- 10.8 vs 13.25 +/- 9.3; p=0.0001) and impaired hand and wrist mobility (Kapandji score 38.05 +/- 10.26 vs 43.90 +/- 8.26, p=0.001). The 2 groups did not differ in global disability or physical and mental scores of the SF36. CONCLUSION: Patients recruited from a patient association have more severe SSc than do hospitalized patients. This finding must be taken into account in the design of surveys and clinical trials. PMID- 20356710 TI - Rapid estimation of left ventricular function using echocardiographic speckle tracking of mitral annular displacement. AB - BACKGROUND: Left ventricular (LV) ejection fraction (EF) by transthoracic two dimensional echocardiography is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) qualitatively correlates with EF and can be measured in patients with poor image quality and dropout. The authors hypothesized that speckle-tracking echocardiography (STE)-derived MAD could quantify EF accurately and tested this hypothesis using cardiac magnetic resonance (CMR) as a reference. METHODS: One hundred eighteen patients undergoing clinical transthoracic echocardiography were screened, and 110 whose mitral annuli was sufficiently well-defined irrespective of LV endocardial visualization underwent CMR within 6 days (85 of 110 in 1 day). Reference CMR EF values were obtained using standard methodology. STE was used to track annular motion throughout the cardiac cycle in the apical 2-chamber and 4-chamber views. To establish the relationship between MAD and CMR EF and to obtain a formula to estimate EF from MAD, regression analysis was performed in a study group of 60 patients with a wide range of EFs. This formula was then used in an independent test group of 50 patients by comparing estimated MAD EF against CMR EF values using Pearson's correlation and Bland-Altman analyses. RESULTS: In the study group, STE MAD correlated highly with CMR EF and resulted in a formula relating MAD to EF. In the test group, estimated EF correlated well with CMR EF (4 chamber, R(2) = 0.64; 2-chamber, R(2) = 0.55), with near-zero bias and acceptable limits of agreement. Intraobserver and interobserver variability were between 5.8% and 12.7%. CONCLUSIONS: STE MAD is a clinically useful tool for quick, easy, robust, and accurate estimates of EF irrespective of LV endocardial definition. PMID- 20356711 TI - Biventricular pacing as bridge to rapid recovery in infancy. AB - The authors present the unique case of an 8-month-old baby diagnosed with severe left ventricular failure of unknown etiology. Due to a lack of organ availability for this age, a mechanical assist device and assessment for cardiac transplantation were not offered. Subsequent comprehensive echocardiographic dyssynchrony assessment and the presence of left bundle branch block were suggestive of response to cardiac resynchronization therapy. Dual-chamber epicardial pacing was initiated, resulting in prompt marked clinical and echocardiographic improvement, which continued until complete normalization of cardiac function. The pacing system was safely turned off 6 months after its implantation. In conclusion, cardiac resynchronization therapy should be considered as a treatment option even in infancy, regardless of the etiology of disease and/or patient age. PMID- 20356712 TI - Contrast enhanced transesophageal echocardiographic guidance of left atrial appendage closure device implantation. AB - The percutaneous implantation of a left atrial appendage closure device offers an alternative to chronic oral anticoagulation in patients with nonvalvular atrial fibrillation and concomitant risk factors for stroke. Transesophageal echocardiography plays a key role in defining left atrial appendage anatomy and in guiding device implantation. The authors describe a case in which contrast enhanced transesophageal echocardiography was critically important in spatially resolving the borders of the left atrial appendage, which ultimately led to successful device implantation with cessation of warfarin therapy. PMID- 20356713 TI - Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling. AB - Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic beta cells in the islets of Langerhans. Although defects in various T cell subsets have been linked to the disease pathogenesis, mechanisms initiating or enhancing the autoimmunity in prediabetes remain poorly understood. To unravel genes and molecular pathways affected by the diabetes-associated autoimmunity, we investigated transcriptomic profiles of prospective whole-blood samples from children who have developed T1D-associated autoantibodies and eventually clinical T1D. Gene-level investigation of the data showed systematic differential expression of 520 probesets. A network-based analysis revealed then a highly significant down-regulated network of genes involved in antigen presentation as well as T-cell receptor and insulin signaling. Finally, detection of dynamic changes in the affected pathways at the early or late phases of autoimmunity showed down-regulation of several novel T1D-associated pathways as well as known key components of immune response. The longitudinal genome-wide data generated in the present study allows the detection of dynamic changes relevant to the disease that may be completely missed in conventional cross-sectional studies or in genome-wide association studies. Taken together, our analysis showed systemic high-level repression of immune response pathways associated with T1D autoimmunity. PMID- 20356714 TI - Plasmid-mediated carbapenem-hydrolysing OXA-48 beta-lactamase in Klebsiella pneumoniae from Tunisia. PMID- 20356715 TI - Characterisation of qnr plasmid-mediated quinolone resistance in Enterobacteriaceae from Italy: association of the qnrB19 allele with the integron element ISCR1 in Escherichia coli. AB - The spread of plasmid-mediated quinolone resistance determinants (qnr-like determinants) was evaluated in a collection of 232 ciprofloxacin-resistant or extended-spectrum beta-lactamase (ESBL)-producing enterobacterial isolates recovered between November 2007 and May 2008 at Padua University Hospital, Italy. qnr genes were mainly found in Klebsiella pneumoniae (68%) and to a lesser extent in Escherichia coli (5.1%). Among the qnrA1, qnrS1 and qnrB19 alleles found, the latter was by far the most frequent. Genetic environment analysis revealed that one qnrB19 gene in E. coli was embedded in an ISCR1 complex class 1 integron. All other qnrB19 genes were flanked by an ISEcp1C region as part of the Tn2012 transposon. qnrA1- and qnrS1-containing strains were not clonally related. Both topoisomerase II mutations and ESBL (mainly SHV-12, TEM-1 and TEM-150 types) were present in most of the qnr-positive strains. qnrB19 is extremely frequent in K. pneumoniae isolates from Italy. In addition, association of qnrB19 with the ISCR1 mobile element in E. coli suggests a broad distribution of this resistance gene in the near future. PMID- 20356716 TI - Comparison of two DNA microarrays for detection of plasmid-mediated antimicrobial resistance and virulence factor genes in clinical isolates of Enterobacteriaceae and non-Enterobacteriaceae. AB - A DNA microarray was developed to detect plasmid-mediated antimicrobial resistance (AR) and virulence factor (VF) genes in clinical isolates of Enterobacteriaceae and non-Enterobacteriaceae. The array was validated with the following bacterial species: Escherichiacoli (n=17); Klebsiellapneumoniae (n=3); Enterobacter spp. (n=6); Acinetobacter genospecies 3 (n=1); Acinetobacterbaumannii (n=1); Pseudomonasaeruginosa (n=2); and Stenotrophomonasmaltophilia (n=2). The AR gene profiles of these isolates were identified by polymerase chain reaction (PCR). The DNA microarray consisted of 155 and 133 AR and VF gene probes, respectively. Results were compared with the commercially available Identibac AMR-ve Array Tube. Hybridisation results indicated that there was excellent correlation between PCR and array results for AR and VF genes. Genes conferring resistance to each antibiotic class were identified by the DNA array. Unusual resistance genes were also identified, such as bla(SHV-5) in a bla(OXA-23)-positive carbapenem-resistant A. baumannii. The phylogenetic group of each E. coli isolate was verified by the array. These data demonstrate that it is possible to screen simultaneously for all important classes of mobile AR and VF genes in Enterobacteriaceae and non Enterobacteriaceae whilst also assigning a correct phylogenetic group to E. coli isolates. Therefore, it is feasible to test clinical Gram-negative bacteria for all known AR genes and to provide important information regarding pathogenicity simultaneously. PMID- 20356717 TI - Manifesto for a European anxiety disorders research network. AB - Despite the size, burden and costs of anxiety disorders, many patients remain unrecognised, and the effectiveness of evidence-based interventions in routine clinical practice can be disappointing. The European College of Neuropsychopharmacology (ECNP) has established the ECNP Network Initiative (ECNP NI) to help meet the goal of extending current understanding of the causes of central nervous system disorders, thereby contributing to improvements in clinical outcomes and reducing the associated societal burden. The Anxiety Disorders Research Network (ADRN) has been adopted within the ECNP-NI: this consensus statement summarises its overall aims and objectives. PMID- 20356718 TI - A coding variant of the novel serotonin receptor subunit 5-HT3E influences sustained attention in schizophrenia patients. AB - Sustained attention as measured by the Continuous Performance Test (CPT) has proved a valuable endophenotype for schizophrenia. Recently pharmacological studies suggested a role of the serotonin (5-HT) 3 receptor in schizophrenia. The 5-HT3 receptors are the only ligand-gated ion channels within the 5-HT receptor family. Applying an endophenotype approach, we investigated a potential impact of the genes of the 5-HT3A and 5-HT3B subunits as well as the novel 5-HT3C, 5-HT3D, and 5-HT3E subunits on CPT performance in subjects with schizophrenia. The study included 196 patients with schizophrenia, 113 of their parents, and 205 healthy controls recruited from community registers. Sustained attention was assessed with the Continuous Performance Test-Identical Pairs (CPT-IP). Assessing functional and coding variants of the 5-HT3 receptor subunit genes, we found the GG genotype of the 5-HT3E subunit gene (rs7627615; Thr86Ala) to be associated with better attentional capacities in subjects with schizophrenia and healthy controls. This study provides additional evidence for a role of the serotonergic system and the 5-HT3 receptor in schizophrenia. PMID- 20356719 TI - Period four metal nanoparticles on the inhibition of biofouling. AB - Biofilms present operational problems to a variety of industrial areas including but not limited to, medicine, water treatment, sensor sensitivity and shipping. Bacterial adhesion resides as a tiny monolayer and builds-up over time with the production of protective slimes known as extracellular polymeric substances (EPS) forming the 'biofilm'. Infection, inefficiency and diminution of quality are caused by biofilms, which have the potential to be prohibitively expensive to repair. The value of an effective coating that prevents the adhesion of bacteria and subsequent fouling is paramount in preserving sensitivity and longevity of a subjected operational substrate. Polymer and sol-gel (SG) based coatings tender a matrix for the introduction of biocides and antimicrobial agents that offer this prevention. They present a relatively cheap and optically clear platform that can then be doped with the antimicrobial agent. This proves useful in transferring across a range of industries that may require a transparent function to the coating. Nanoparticles offer a means of new line research in combating biofouling and biocorrosion with interest stemming from silver metal nanoparticles (MNPs) that already offer antimicrobial property. The aim of this work is to investigate period four metal nanoparticles for any antimicrobial potential they offer, in the prevention of fouling in the early stages. The research presented herein uses a range of period four MNPs synthesised through an adapted polyol reduction, which have then been doped into SG coatings and tested for their efficacy in preventing levels of biofouling. After a 7-day freshwater study results showed that MNPs prevent levels of biofouling upto 125% compared to the SG blank. The work uses bacterial enumeration, minimum inhibitory concentration (MIC), surface characterisation and slime and biomass analysis to complete a range of studies in assessing the level of fouling observed on the test substrates. PMID- 20356720 TI - Inhibition of delta-aminolevulinate dehydratase is not closely related to the development of hyperglycemia in alloxan-induced diabetic mice. AB - Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing beta-cells. The aim of this study was to investigate acute (after 24h) and sub-acute (after seven days) effects of 200mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood delta-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal delta-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of delta-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on delta-ALA-D activity is, at least partially, related to the oxidation of the enzyme's essential thiol groups. Blood delta-ALA-D activity was significantly inhibited only 24h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice. PMID- 20356721 TI - The association of fatty acid deficiency symptoms (FADS) with actual essential fatty acid status in cheek cells. AB - Seven clinical symptoms have been utilised in several studies as a means of potentially identifying children with a deficiency in essential polyunsaturated fatty acids (PUFAs). The purpose of this study was to investigate whether there was any correlation between parental reports of the frequency of these seven 'fatty acid deficiency symptoms' (FADS) with actual levels of fatty acids in buccal cell samples of 450 children aged 8-10 years old. Additionally, the relationship between FADS and cognitive test performance, ratings of attention and behaviour and other somatic complaints were explored. The severity of reported FADS was not related to the levels of omega-6 or omega-3 in buccal cell samples. There was a relationship between parental reports of child behaviour and reported FADS; with high FADS being related to higher ratings of behaviour problems. Using FADS as a marker of PUFA deficiency may not be appropriate especially when assessing typically developing children. PMID- 20356722 TI - Additional cost benefits of chest physician-operated thoracic ultrasound (TUS) prior to medical thoracoscopy (MT). PMID- 20356723 TI - Decoding the function of nuclear long non-coding RNAs. AB - Long non-coding RNAs (lncRNAs) are mRNA-like, non-protein-coding RNAs that are pervasively transcribed throughout eukaryotic genomes. Rather than silently accumulating in the nucleus, many of these are now known or suspected to play important roles in nuclear architecture or in the regulation of gene expression. In this review, we highlight some recent progress in how lncRNAs regulate these important nuclear processes at the molecular level. PMID- 20356725 TI - Beyond neoclassical economics: Social process, agency and the maintenance of order in an Australian illicit drug marketplace. AB - BACKGROUND: The dominant Australian approaches to understanding illicit drug marketplaces are surveillance and criminological research. These approaches rely on the elementary neoclassical economic model of the market which focuses primarily on supply and demand. In this paper, we draw on anthropological and sociological research to develop an alternative framework for understanding Australian illicit drug marketplaces that emphasises their constituent processes. METHODS: The paper draws on two years of ethnographic research among heroin user/sellers of Vietnamese ethnicity in an Australian heroin marketplace. RESULTS: Trade and barter were key modes of exchange in this marketplace. We identified active negotiation and bargaining over price on the basis of social relationships, with dealers and customers actively working to develop and maintain such ties. Dealers set price collectively and this was shaped by moral and cultural elements such as notions of a 'fair' price. Social processes and relations as well as shared cultural expectations helped to generate trust and maintain order in the marketplace. CONCLUSION: Our ethnographic research suggests that the dominant Australian approaches to the study of illicit drug markets, with their reliance on the elementary neoclassical economic market model, ignore the social processes and social relations through which such sites are made and remade. Nor do they adequately capture the complex character of the subjects who act within these sites. If we are to expand our understanding of illicit drug markets and marketplaces in Australia, we must look beyond the conceptions offered by surveillance and criminological approaches. PMID- 20356724 TI - Genome architecture and the role of transcription. AB - During development or in response to environmental stimuli, eukaryotic genes change both their expression and position in 3D nuclear space. Then, is a gene transcribed because of its position, or is position determined by transcription? Are genes stochastically or deterministically engaged in transcription cycles? Recent results confirm that RNA polymerases and their transcription factors play central roles in genome organization, and that stochastic events can give rise to apparently deterministic expression. As is so often the case in biology, structure both determines function and is influenced by it. PMID- 20356726 TI - Analysis of the combustion of sewage sludge-derived fuel by a thermogravimetric method in China. AB - The treatment and disposal of sewage sludge are significant environmental problems in China. The reuse of sewage sludge for fuel could be an effective solution. The aim of this study was to characterize the behavior of sludge derived fuel during combustion by a thermogravimetric method. The combustion profiles obtained showed four obvious weight loss regions. The results of dynamics analysis showed that first-order reactions together with Arrhenius' law explained reasonably well the different stages of weight loss in the samples. Three temperature regions (162-327 degrees C, 367-445 degrees C, and 559-653 degrees C for sawdust and 162-286 degrees C, 343-532 degrees C, and 609-653 degrees C for coal) in each derivative thermogravimetry (DTG) curve corresponded well with the Arrhenius equation. The reactivity of sludge was lower than that of samples containing sawdust, but higher than that of coal-containing samples. These data demonstrate that sludge-derived fuel has better combustion characteristics than sludge, sawdust, or coal. PMID- 20356727 TI - Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. AB - Human beings and animals have sensitive olfactory systems that can sense and identify a variety of odors. The purpose of this study is to combine biological cells with micro-chips to establish a novel bioelectronic nose system for odor detection by electrophysiological sensing measurements of olfactory tissue. In our experiments, 36-channel microelectrode arrays (MEAs) with the diameter of 30 microm were fabricated on the glass substrate, and olfactory epithelium was stripped from rats and fixed on the surface of MEA. Electrophysiological activities of olfactory receptor neurons in intact epithelium were measured through the multi-channel recording system. The extracellular potentials of cell networks could be effectively analyzed by correlation analysis between different channels. After being stimulated by odorants, such as acetic acid and butanedione, the olfactory cells generate different firing modes. These firing characteristics can be derived by time-domain and frequency-domain analysis, and they were different from spontaneous potentials. The investigation of olfactory epithelium can provide more information of olfactory system for artificial olfaction biomimetic design. PMID- 20356728 TI - Electrochemical biosensor microarray functionalized by means of biomolecule friendly photolithography. AB - Microfabrication permits the incorporation of dense electrode arrays in microsystems and small volume diagnostic devices. However, the specific functionalization of arbitrary shape electrodes with different biomolecules remains a challenging issue. In the present work, the problem of fabricating closely spaced microelectrodes (20 microm sensor diameter and 20 microm-spaced interdigitated electrodes array) that can be modified selectively in order to create multi-analyte sensor arrays is addressed by employing a biomolecule friendly photolithographic procedure for the sequential immobilization of different biomolecules onto separated electrodes of the same array. The concept was demonstrated with selective detection of oligonucleotides for breast cancer gene mutation detection, the hormone T4 detected with specific antibodies and sarcosine and glucose detected with specific enzymes immobilized in two-analyte arrays in order to assure that the method is compatible with all the types of biorecognition molecules used in biosensors. Electrochemical techniques were used in this array, because of the low cost, high sensitivity and easy miniaturization of these transducers. Although the array was composed of only two sets of electrodes, the results demonstrate that the method proposed is generic and could be used for patterning of electrochemical multi-analyte biosensors at even higher resolution. PMID- 20356729 TI - Rapid and sensitive electrochemical sensing of DNA damage induced by V2O5 nanobelts/HCl/H2O2 system in natural dsDNA layer-by-layer films. AB - The detection of DNA damage is one of the most important topics in the DNA research fields. In the present work, oppositely charged natural dsDNA and poly(diallyldimethyl ammonium chloride) (PDDA) were assembled into (PDDA/dsDNA)(3) layer-by-layer films on electrode surface, and Ru(bpy)(3)(2+) and Co(phen)(3)(3+) in solution were used as electroactive probes to detect oxidative damage of natural dsDNA in the films after incubation of the films in V(2)O(5) nanobelts/HCl/H(2)O(2) solution. The mechanism of DNA oxidative damage caused by the V(2)O(5) nanobelts/HCl/H(2)O(2) system was similar to that of Fenton-type reaction. The reaction of V(2)O(5) nanobelts with HCl would produce V(IV), and the produced V(IV) would further react with H(2)O(2), generating hydroxyl radicals (OH*) as in the Fenton-type reaction, which could severely damage DNA in the films. The present work provided an in vitro model system to mimic the pathway of DNA damage in real bioprocess through a simple electrochemical approach combined with layer-by-layer assembly. This approach also showed promising applications in rapid and sensitive screening of new nanomaterials and chemicals in vitro for their potential genotoxicity. PMID- 20356730 TI - Direct electrochemistry of horseradish peroxidase immobilized on the layered calcium carbonate-gold nanoparticles inorganic hybrid composite. AB - A mediator-free hydrogen peroxide (H(2)O(2)) biosensor was fabricated based on immobilization of horseradish peroxidase (HRP) on layered calcium carbonate-gold nanoparticles (CaCO(3)-AuNPs) inorganic hybrid composite. The proposed biosensor showed a strong electrocatalytic activity toward the reduction of H(2)O(2), which could be attributed to the favored orientation of HRP in the well-confined surface as well as the high electrical conductivity of the resulting CaCO(3) AuNPs inorganic hybrid composite. The hybrid composite was obtained by the adsorption of AuNPs onto the surfaces of layered CaCO(3) through electrostatic interaction. The key analytical parameters relative to the biosensor performance such as pH and applied potential were optimized. The developed biosensor also exhibited a fast amperometric response (3s), a good linear response toward H(2)O(2) over a wide range of concentration from 5.0x10(-7) to 5.2x10(-3)M, and a low detection limit of 1.0x10(-7)M. The facile, inexpensive and reliable sensing platform based on layered CaCO(3)-AuNPs inorganic hybrid composite should hold a huge potential for the fabrication of more other biosensors. PMID- 20356731 TI - Artificial hydrogenases. AB - Decades of biophysical study on the hydrogenase (H(2)ase) enzymes have yielded sufficient information to guide the synthesis of analogs of their active sites. Three families of enzymes serve as inspiration for this work: the [FeFe] H(2)ases, [NiFe]-H(2)ases, and [Fe]-H(2)ases, all of which feature iron centers bound to both CO and thiolate. Artificial H(2)ases affect the oxidation of H(2) and the reverse reaction, the reduction of protons. These reactions occur via the intermediacy of metal hydrides. The inclusion of amine bases within the catalysts is an important design feature that is emulated in related bioinspired catalysts. Continuing challenges are the low reactivity of H(2) toward biomimetic H(2)ases. PMID- 20356732 TI - The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma. AB - The efficiency of a Zn(II)-phthalocyanine disulphide (C11Pc), a compound with both phthalocyanine units bearing seven hexyl chains and a sulphur terminated C11 chain, as a photodynamic therapy (PDT) agent was investigated in C57 mice bearing a sub-cutaneously transplanted amelanotic melanoma. The phthalocyanine was intravenously injected at a dose of 1.5 micromol/kg body weight either free or bound to gold nanoparticles, using a Cremophor emulsion as a delivery vehicle. Biodistribution studies at selected post-injection times showed that the nanoparticle-associated C11Pc was recovered in significantly larger amounts from all the examined tissues and the serum and yielded a greater selectivity of tumour targeting: thus, the ratio between the amount of phthalocyanine recovered from the amelanotic melanoma and the skin (peritumoural tissue) increased from 2.3 to 5.5 from the free to the gold nanoparticle-bound C11Pc at 24 h after injection. PDT studies with the C11Pc-loaded amelanotic melanoma showed a markedly more significant response of the tumour in the mice that had received the nanoparticle-bound photosensitiser; the PDT effect was especially extensive if the irradiation was performed at 3h after C11Pc injection when large phthalocyanine amounts were still present in the serum. This suggests that the PDT promoted by C11Pc predominantly acts via vascular damage at least in this specific animal model. This hypothesis was fully confirmed by electron microscopy observations of tumour specimens obtained at different times after the end of PDT, showing an extensive damage of the blood capillaries and the endothelial cells. PMID- 20356733 TI - Anaerobic digestion of brewery primary sludge to enhance bioenergy generation: a comparison between low- and high-rate solids treatment and different temperatures. AB - Anaerobic digestion of brewery wastewater solids in the form of primary sludge was investigated for its potential as a source of energy (methane). We operated a low-rate (hydraulic retention time (HRT)=solids retention time (SRT)) continuously stirred anaerobic digester (CSAD) and a high-rate (SRT>HRT) anaerobic sequencing batch reactor (ASBR) in parallel for 250 days. We found that high-rate anaerobic digestion was beneficial for solids-rich waste flows even during a long-term operating period that included a shock load of nonbiodegradable total solids. The ASBR biomass achieved a higher specific methanogenic activity compared to the CSAD biomass (0.257+/-0.043 vs. 0.088+/ 0.008 g CH(4)-COD g(-1)VSS d(-1)), which aided in stability during the shock load with total solids. The methane yield for the ASBR was 40-34% higher than for the CSAD (0.306 vs. 0.219 l CH(4)g VS(-1) fed for days 1-183 and 0.174 vs. 0.130 l CH(4)g VS(-1) fed for days 184-250, respectively). Finally, we operated an ASBR for an additional 295 days to evaluate the effect of temperature variation on system stability. A stable performance was achieved between the operating temperatures of 22-41 degrees C. PMID- 20356734 TI - Combined effect of inorganic carbon limitation and inhibition by free ammonia and free nitrous acid on ammonia oxidizing bacteria. AB - The inhibitory effect of free ammonia (NH(3) or FA) and free nitrous acid (HNO(2) or FNA) on the ammonia oxidizing bacteria (AOB) and the dependence of the AOB activity on the concentration of total inorganic carbon (TIC) are well established. In contrast, less is know about the effect of high FA and FNA concentrations in combination with TIC limitation. Respirometric tests performed with an enriched AOB sludge (81% of AOB as measured with fluorescent in situ hybridization) established that AOB inhibition by FA under TIC limitation was higher than under non-limiting TIC conditions (Haldane inhibition coefficients of 139 and 376 mg NH(3)L(-1)). AOB affinity for FA decreased under TIC limitation conditions (half-saturation coefficient of 0.28 mg NH(3)L(-1) without TIC limitation and 4.3 mg NH(3)L(-1) with TIC limitation). Higher inhibition by FNA was observed when TIC was limited since the non-competitive inhibition coefficient decreased from 1.31 mg HNO(2)L(-1) (without TIC limitation) to 0.21 mg HNO(2)L(-1) (with TIC limitation). This study demonstrates that AOB inhibitions by FA and FNA are amplified with TIC limitation and consequently, AOB dynamics are strongly modified under TIC limitation conditions. PMID- 20356735 TI - New diterpenoids from Caesalpinia species and their cytotoxic activity. AB - Chemical investigation on Caesalpinia crista afforded two new diterpenoids, 6beta cinnamoyloxy-7beta-acetoxyvouacapen-5alpha-ol and 6beta,7beta dibenzoyloxyvouacapen-5alpha-ol and on Caesalpiniapulcherrima another new diterpenoid, 12-demethyl neocaesalpin F along with several known constituents. The structures of the new compounds were settled from their 1D and 2D NMR spectral data. The cytotoxicity of these compounds was measured on two different cancer cell lines. PMID- 20356736 TI - Synthesis and structure-activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARalpha selective activators- PPARalpha and PPARgamma selectivity modulation. AB - The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPARalpha/gamma dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPARalpha versus PPARgamma. Potent, highly selective PPARalpha activators 2a and 2l, as well as PPARalpha activators with significant PPARgamma activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed. PMID- 20356737 TI - Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase. AB - Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP binding site, are described in this communication. Novel, substituted 5-(1H pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB. PMID- 20356738 TI - Synthesis and antibacterial activities of a novel alkylide: 3-O-(3-aryl-2 propargyl) and 3-O-(3-aryl-2-propenyl)clarithromycin derivatives. AB - A series of novel 3-O-(3-aryl-E-2-propenyl)clarithromycin derivatives 8 and 3-O (3-aryl-2-propargyl)clarithromycin derivatives 11 were designed, synthesized, and evaluated for their in vitro antibacterial activities. Compared with 8c and 11c (Ar was 5-pyrimidyl), 3-O-(3-(5'-pyrimidyl)-Z-1-propenyl) counterpart 6c displayed 4- to 64-fold more potent activities against erythromycin-susceptible Staphylococcus aureus and Streptococcus pneumoniae. Moreover, the activities of 6c, 8c, and 11c against erythromycin-resistant S. aureus and S. pneumoniae were in general 4-fold higher than those of the reference compound, clarithromycin and azithromycin. PMID- 20356739 TI - Imidazoacridin-6-ones as novel inhibitors of the quinone oxidoreductase NQO2. AB - The purpose of the work was to identify novel inhibitors of the enzyme NQO2. Using computational molecular modelling, a QSAR (R(2)=0.88) was established, relating inhibitory potency with calculated binding affinity. From this, the imidazoacridin-6-one, NSC660841, was identified as the most potent inhibitor of NQO2 yet reported (IC(50)=6 nM). PMID- 20356740 TI - Chlorin e6-cholesterol conjugate and its copper complex. Simple synthesis and entrapping in phospholipid vesicles. AB - Synthesis of 13'[(cholest-5-en)-3beta-yloxyethoxycarbamoyl]-chlorin e6 starting from methylpheophorbide and 3beta(2-hydroxy)-ethoxycholest-5-ene is presented, as well as the preparation of related copper complex. Both conjugates obtained may be simply incorporated in phosphatidyl choline vesicles. PMID- 20356741 TI - Synthesis and anti-tumor activities of methyl 2-O-aryl-6-O-aryl'-D glucopyranosides. AB - A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC(50) values of 14, 12, and 10 micromol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure-activity relationship analysis indicates that the two free hydroxyl groups on the D-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting 'on-off' mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored. PMID- 20356742 TI - Episodic myoglobinuria in a primary gamma-sarcoglycanopathy. AB - Episodic myoglobinuria is a well-recognized complication of metabolic myopathies, and may occur in Duchenne and Becker dystrophies, but has only rarely been associated with limb-girdle muscular dystrophy. We describe an unusual presentation, with rhabdomyolysis, of limb-girdle muscular dystrophy (LGMD). We evaluated a patient for progressive muscle weakness and tenderness, with myoglobinuria one week after initial presentation. Immunohistochemistry on muscle tissue revealed absent staining for gamma-sarcoglycan, confirmed by detection of a homozygous mutation in the gamma-sarcoglycan gene. Myoglobinuria has been previously reported only twice in LGMD. It is therefore important to recognize that myoglobinuria may be a symptom of a muscular dystrophy, and muscle biopsy and immunostaining are important tools for diagnosis. PMID- 20356744 TI - Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson's disease. AB - Motor cortex excitability was assessed in 12 patients with Parkinson's disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated ("ON") and when immobile after medication withdrawal ("OFF"). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in "ON" and "OFF" states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either "ON" or "OFF" states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores. PMID- 20356743 TI - The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond. AB - An increasing body of research on autophagy provides overwhelming evidence for its connection to diverse biological functions and human diseases. Beclin 1, the first mammalian autophagy protein to be described, appears to act as a nexus point between autophagy, endosomal, and perhaps also cell death pathways. Beclin 1 performs these roles as part of a core complex that contains vacuolar sorting protein 34 (VPS34), a class III phosphatidylinositol-3 kinase. The precise mechanism of Beclin 1-mediated regulation of these cellular functions is unclear, but substantial progress has recently been made in identifying new players and their functions in Beclin 1-VSP34 complexes. Here we review emerging studies that are beginning to unveil the physiological functions of Beclin 1-VPS34 in the central control of autophagic activity and other trafficking events through the formation of distinct Beclin 1-VPS34 protein complexes. PMID- 20356745 TI - Transvenous embolization of an intraorbital arteriovenous fistula using Onyx. AB - We report a 61-year-old male with an intraorbital arteriovenous fistula. Due to the close proximity of the arterial feeder to the central retinal artery, and the tiny calibre of the draining branches of the superior ophthalmic vein, transvenous embolization of the fistula by Onyx was preferred. The procedure completely obliterated the shunt and the patient had complete relief of symptoms within 6 months. PMID- 20356746 TI - L-Dopa therapy increases homocysteine concentration in cerebrospinal fluid from patients with Parkinson's disease. AB - To investigate the effect of L-3,4-dihydroxyphenylalanine (L-dopa) therapy on homocysteine (HC) concentration in patients with Parkinson's disease (PD), the concentrations in cerebrospinal fluid (CSF) of total HC and methionine (Met) were compared between 18 patients with PD before and after treatment with L-dopa and 16 neurologically normal control patients. Concentrations of total HC in patients with PD were significantly higher following L-dopa therapy (169+/-27 nM) than before treatment (111+/-22 nM) and than in controls (85+/-25 nM) (patients with PD before L-dopa treatment vs. controls, p<0.005; patients with PD after L-dopa treatment vs. before treatment, p<0.0001). Conversely, concentrations of total Met in patients with PD were significantly lower after L-dopa therapy (5.3+/-1.7 microM) than before L-dopa therapy (6.8+/-1.9 microM) (p<0.001). These findings in patients with PD suggest that L-dopa therapy enhances intracerebral methylation and elevates concentration of HC. PMID- 20356747 TI - Influence of age on thermal thresholds, thermal pain thresholds, and reaction time. AB - The main goals of this study were to investigate the effect of age on thermal and thermal pain thresholds and reaction time, and to analyze the influence of age related changes in reaction time on thermal and thermal pain thresholds. Thermal thresholds (warm/cold) and thermal pain thresholds (hot/cold) were evaluated by the method of limits. Visual reaction time was evaluated in a similar way by a customized computer program. In total, 274 normal subjects (23-87 years old) were recruited. Thermal thresholds, thermal pain thresholds, and reaction time were all related to age. While warm and cold thresholds and cold pain thresholds increased with age, hot pain thresholds decreased with age. The age-related change in reaction time was insufficient to explain the age-related changes in thermal and thermal pain thresholds. In conclusion, age affects thermal and thermal pain thresholds independently of reaction time. PMID- 20356748 TI - Multiple symptomatic vertebral artery loops treated with posterior cervical fusion. AB - Multiple symptomatic vertebral artery (VA) loops are rare and their management is challenging. A 55-year-old man presented with a 5-year history of frequent episodes of presyncope and mild left C5 radiculopathy that was exacerbated by flexion or extension of his neck. Examination revealed complex left VA loops at C2/3 and C4. The patient underwent posterior cervical fusion which resolved his presyncope and improved his radiculopathy. Posterior cervical fusion is an option for management of patients suffering from symptoms secondary to multiple VA loops. PMID- 20356749 TI - Spontaneous regression of an anterior skull base mass. AB - Spontaneous regression of an intracranial mass is rare. We report a 77-year-old man with spontaneous regression of an anterior skull base mass suspected to be an inflammatory pseudotumor. The patient attended our outpatient department approximately once per month for a regular check-up following a brain stem infarction. A small mass was detected at the anterior skull base by MRI. The mass gradually grew to about 3 cm over a period of 5 years and then remained stable for 3 years. Thereafter, the mass showed spontaneous regression 8 years after it was first visible on MRI. 'Inflammatory pseudotumor' is a broad category and the natural history of these lesions is highly variable. Although the definition does include some types of malignant lesion, most masses are benign lesions that can regress spontaneously, as in our patient. A 'wait-and-see' policy is appropriate for such patients. PMID- 20356750 TI - Regulation and role of organic anion-transporting polypeptides (OATPs) in drug delivery at the choroid plexus. AB - The organic anion-transporting polypeptides (rodents: Oatps; human: OATPs) belong to the growing family of organic anion/prostaglandin transporters and are important components of the active efflux transport system at the choroid plexus epithelial cells. OATPs facilitate the elimination of xenobiotics and endogenous waste from the cerebrospinal fluid and prevent waste accumulation in the central nervous system (CNS). This review summarizes the structures, regulations and roles of Oatps/OATPs at the choroid plexus in drug delivery to the CNS. PMID- 20356751 TI - CT metal artefact reduction of total knee prostheses using angled gantry multiplanar reformation. AB - This study was designed to determine whether or not acquiring CT images of total knee prostheses by using an angled gantry and multiplanar reformation can reduce beam hardening artefact. A CT phantom was created with a total knee prosthesis suspended in gelatine with a known attenuation. CT data was acquired with a gantry angled at 0 degrees, 5 degrees, 10 degrees and 15 degrees in both craniocaudal oblique planes. Axial images where then reformatted from these datasets. Two independent observers selected regions of interest to measure the mean and standard deviation (SD) of attenuation in the gelatine for all reformatted axial images. Artefact was measured as SD of the background attenuation and areas under the curve of SD for each gantry angle acquisition were compared. Inter-observer reliability was excellent (ICC=0.89, CI 0.875 0.908). The most accurate mean attenuation values for tissues around a TKR were obtained with a CT gantry using 10 degrees to 15 degrees anteroinferior to posterosuperior angulation. The smallest area under the curve for SD of attenuation for the whole prosthesis, and the femoral component in isolation, was obtained with a 5 degrees gantry angle in the same direction. The smallest area under the curve for the tibial component in isolation occurred with a gantry angle of 15 degrees. We conclude that acquiring CT data with a gantry angle can reduce metal artefact around a TKR. Optimal overall metal artefact reduction can be achieved with a small angle from anteroinferior to posterosuperior. Further selective artefact reduction around the tibial component can be achieved with larger angles. PMID- 20356752 TI - Trypanoside, anti-tuberculosis, leishmanicidal, and cytotoxic activities of tetrahydrobenzothienopyrimidines. AB - The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4 yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug optimization and drug-development efforts for use as therapeutic agents in developing countries. PMID- 20356753 TI - Cloning and characterization of cDNAs encoding for long-chain saturated acyl-ACP thioesterases from the developing seeds of Brassica juncea. AB - Four types of cDNAs corresponding to the fatty acyl-acyl carrier protein (ACP) thioesterase (Fat) enzyme were isolated from the developing seeds of Brassica juncea, a widely cultivated species amongst the oil-seed crops. The mature polypeptides deduced from the cDNAs showed sequence identity with the FatB class of plant thioesterases. Southern hybridization revealed the presence of at least four copies of BjFatB gene in the genome of this amphidiploid species. Western blot and RT-PCR analyses showed that the BjFatB class thioesterase is expressed poorly in flowers and leaves, but significantly in seeds at the mid-maturation stage. The enzymatic activities of different BjFatB isoforms were established upon heterologous expression of the four BjFatB CDSs in Escherichia coli K27fadD88, a mutant strain of fatty acid beta-oxidation pathway. The substrate specificity of each BjFatB isoform was determined in vivo by fatty acid profile analyses of the culture supernatant and membrane lipid of the recombinant K27fadD88 and E. coli DH10B (fadD(+)) clones, respectively. The BjFatB1 and BjFatB3 were predominantly active on C18:0-ACP substrate, whereas BjFatB2 and BjFatB4 were specific towards C18:0-ACP as well as C16:0-ACP. These novel FatB genes may find potential application in metabolic engineering of crop plants through their over-expression in seed tissues to generate stearate-rich vegetable fats/oils of commercial importance. PMID- 20356754 TI - Obtaining an upper estimate of the survival benefit associated with surgery for mesothelioma. AB - OBJECTIVE: This study aimed to obtain an upper estimate of any survival benefit conferred by resection in patients with a diagnosis of malignant pleural mesothelioma. METHODS: We analysed published data concerning survival from diagnosis among four groups of patients with mesothelioma, identified by ascending level of intervention: (A) no surgery; (B) thoracotomy but no resection; (C) resection but no adjuvant treatment; and (D) resection as part of multimodality treatment. Mean survival was estimated for each of these four groups. Mean survival was also estimated for all those having resection (groups C and D) and for all those not having a resection (groups A and B). RESULTS: Mean survival was 16.8, 17.8 and 17 months for those having no surgery, thoracotomy alone and resection with no adjuvant treatment respectively (groups A, B and C) and 32.9 months for those having multimodality treatment (group D). Mean survival was 25.6 months in those who had resection and 17.1 months in those that did not. The survival advantage of any management that included surgical resection was estimated as being no more than 9 months. This is the most optimistic estimate and requires all observed differences in survival to be attributed to the effect of treatment and none to selection for treatment. Furthermore, within this upper estimate is included any benefit from other components of multimodality treatment. CONCLUSIONS: Given the burden of morbidity of resection in the management of pleural mesothelioma, this most optimistic estimate of the magnitude of any survival benefit should be taken into account in any policy decision, in clinical trial proposals and in strategies adopted by clinical teams. PMID- 20356755 TI - Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age. AB - OBJECTIVES: The optimal pulmonary valved conduit for infants and small children remains controversial. This report compares the initial insertion outcome of small caliber bovine jugular vein (BJV) (12-14 mm) with pulmonary homografts (PHs) (10-15 mm) in patients under age 2. METHODS: From December 1998 to August 2009, 84 children (mean age 8.4 + or - 8.5 months) received BJV (n=51) or PH (n=32) conduits. Mean Z score for BJV was 2.2 (range: -0.8 to 3.3) and for PH 2.1 (range: 0.8-4.2; P=0.2). The two cohorts were similar with respect to age, BSA, conduit indication, bypass and cross-clamp time. Graft dysfunction is defined as right ventricular outflow tract obstruction with peak echo-Doppler gradient >40 mmHg and/or grade III/IV conduit valve regurgitation. Graft failure is defined as need for conduit replacement or need for catheter or surgical re-intervention. Follow-up was greater in number in homografts (BJV, 4.4 + or - 3.0 years vs PH, 5.9+/-3.6 years; P=0.05). RESULTS: Early and late mortality were similar (BJV, 80%; PH 88%; P=0.55). No death was graft related. Freedom from dysfunction was improved at 5 and 10 years with BJV (BJV, 90% at 85% vs PH, 71% and 24% P<0.05). Conduit failure trended higher in the PH cohort at 5 and 10 years (BJV, 85% and 67% vs PH, 75% and 45%; P=0.06). Freedom from explantation was significantly better for BJV patients (BJV, 85% vs PH, 47% P<0.001. Freedom from distal conduit stenosis was similar (BJV, 52% vs PH, 44% P=0.36). CONCLUSIONS: This study suggests that the early performance of small BJV may be more advantageous than homografts. A BJV conduit is an appropriate first choice for conduit replacement in patients less than 2 years of age. PMID- 20356756 TI - Prognostic value of pathologic characteristics and resection margins in tracheal adenoid cystic carcinoma. AB - OBJECTIVE: We investigate the influence of tumour and resection characteristics on survival in adenoid cystic carcinoma (ACC) of the trachea. METHODS: A retrospective study of 12 laryngotracheal, 58 tracheal and 38 carinal resections for primary ACC in 108 consecutive operative survivors between 1962 and 2007 was conducted. Postoperative radiotherapy was administered to 82% of patients (89/108). Depth of invasion, extramural extent, organ invasion, perineural growth, margin status and lymph node involvement were described. RESULTS: The tumour was intramural in 15% (16/108), extramural in 85% (92/108) and invaded adjacent organs in 20% (22/108). Airway margins were grossly positive in 9 (8%), microscopically positive in 59 (55%) and negative in 40 (37%) of 108 resections. Adventitial (radial) margins of transmural sections were grossly positive in 3 (3%), microscopically positive in 95 (88%) and negative in 10 (9%) cases. Perineural growth was present in 37 (34%) and absent in 12 (11%); it was not observed in 59 (55%) cases. Lymph nodes were positive in 16 (15%) and negative in 45 (42%) cases; it was not sampled in 47 (44%) cases. Median overall survival (OS) and disease-free survival (DFS) for the entire group were 17.7 and 10.2 years, respectively. OS was longer after resection with: negative airway margins (20.4 vs 13.3 years, P=0.028) and negative radial margins (21.7 vs 13.3 years, P=0.050); absence of extramural disease (21.7 vs 13.3 years, P=0.007), perineural growth (22.8 vs 7.5 years, P=0.011) or lymph node metastases (16.8 vs 6.1 years, P=0.017). DFS was longer after resection with: negative airway margins (16.6 vs 9.3, P=0.005) and absence of extramural disease (17.9 vs 9.3 years, P=0.008), perineural growth (17.9 vs 6.6 years, P=0.033) or lymph node metastases (10.2 vs 3.0 years, P=0.005). CONCLUSIONS: After tracheal resection for ACC, limited tumour extent and complete resection are associated with longer overall and disease-free survival. Long-term survival (>10 years), however, is also observed after tracheal resection of locally advanced ACC. PMID- 20356757 TI - Echo rejection score: new echocardiographic approach to diagnosis of heart transplant rejection. AB - OBJECTIVE: The gold standard test in the diagnosis of heart transplant rejection is right ventricular (RV) myocardial biopsy, which is an invasive, time consuming, expensive method. In an effort to find a reliable method to minimise the sequential use of myocardial biopsy, we assessed the main echocardiographic indices for the detection of allograft rejection. MATERIALS AND METHODS: Fifty myocardial specimens were examined in this prospective study, which assessed the prominent echocardiographic parameters propounded by previous studies as indicators of rejection. Prior to biopsy, all the patients underwent preoperative transthoracic echocardiography. The accuracy of the echocardiographic indices was compared with that of myocardial biopsy indices as the gold standard. At three myocardial segments, namely, RV base, interventricular septal (Sep) base and lateral left ventricular (Lat) base, peak systolic strain (RV-S, Lat-S and Sep-S) was measured. In addition, time to systole (TS) was measured at the same three segments, yielding the three variables of RV-TS, Sep-TS and Lat-TS. RESULTS: Our logistic regression model revealed that the four factors of Lat-S (%), Sep-TS (ms), posterior wall thickness (PWT; mm) and left ventricular mass index (LVMI; g m(-2)) could denote heart transplant rejection. We devised a new index, the echo rejection score, using the following formula: [(PWT+LVMI)-(Lat-S+Sep-TS)]. This new formula has an area under a curve of 0.932 and a cut-off point of 0; it yields a sensitivity of 100.0%, specificity of 71.0%, positive predictive value of 67.9% and a negative predictive value of 100.0%. If the echo rejection score is >0, there is a 67.9% possibility that a cardiac transplant patient is presenting with allograft rejection, while a score < or =0 denotes a 100% improbability of rejection. CONCLUSION: Our proposed method for screening patients at risk of acute cardiac rejection with echo rejection score showed a good sensitivity in detection of graft rejection. However, further study is required to determine if it can be used as an adjunct to the myocardial biopsy. PMID- 20356758 TI - Exercise ventilatory inefficiency and mortality in patients with chronic obstructive pulmonary disease undergoing surgery for non-small-cell lung cancer. AB - OBJECTIVE: Surgical resection is the treatment of choice to cure patients with non-small-cell lung cancer (NSCLC); nevertheless, the assessment of the lower limit of surgical tolerance remains difficult. Ventilatory inefficiency (measured as the ventilation to CO(2) production ratio (V'(E)/V'(CO2) slope) is a survival predictor in pulmonary hypertension (PH) and chronic heart failure (CHF) and is considered a marker of PH in chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of V'(E)/V'(CO2) slope as preoperative mortality and morbidity predictor in COPD patients submitted to lung resection for NSCLC and considered operable according to current standards. METHODS: A retrospective analysis was performed in 145 consecutive COPD patients with lung cancer (128 males and 17 females), with a mean age of 64 years (range: 41-82 years) who were referred for preoperatory evaluation. Because of bronchial obstruction or reduced pulmonary diffusion capacity for carbon monoxide (D(L,CO)), all these patients were considered operable only after a cardiopulmonary exercise test showed a preserved cardiopulmonary function. RESULTS: A total of 98 lobectomies, eight bilobectomies and 39 pneumonectomies (13 left and 26 right) were performed. Twenty-one patients (14.5%) suffered severe cardio-respiratory complications; 15/106 patients (14.2%) after lobectomy/bilobectomy and 6/39 (15.4%) after pneumonectomy. Five patients (3.4%) died within 30 days after surgery (3/106 after lobectomy/bilobectomy (2.8%) and 2/39 after pneumonectomy (5.1%)). Considering all functional parameters before surgery and the postoperative predicted values, a logistic regression analysis individuated the V'(E)/V'(CO2) slope as the only independent mortality predictor (odds ratio (OR): 1.24 z=2.77; p<0.007). The V'(O2 peak) was instead the best predictor for the occurrence of severe cardiopulmonary postoperative complications (OR: 0.05, z=-2.39, p<0.02). CONCLUSIONS: In COPD patients, a high V'(E)/V'(CO2) slope before lung resection is an independent mortality predictor even in the presence of an acceptable cardiopulmonary performance. COPD patients with high V'(E)/V'(CO2) slope before surgery must be carefully screened to exclude pulmonary hypertension, especially before surgical procedures with large parenchymal exeresis. PMID- 20356759 TI - Effects of low-level light therapy on streptozotocin-induced diabetic kidney. AB - Hyperglycemia causes oxidative damage in tissues prone to complications in diabetes. Low-level light therapy (LLLT) in the red to near infrared range (630 1000nm) has been shown to accelerate diabetic wound healing. To test the hypothesis that LLLT would attenuate oxidative renal damage in Type I diabetic rats, male Wistar rats were made diabetic with streptozotocin (50mg/kg, ip), and then exposed to 670nm light at a dose of 9J/cm(2) once per day for 14weeks. The activity and expression of catalase and the activity of Na K-ATPase increased in kidneys of light-treated diabetic rats, whereas the activity and expression of glutathione peroxidase and the expression of Na K-ATPase were unchanged. LLLT lowered the values of serum BUN, serum creatinine, and BUN/creatinine ratio. In addition, LLLT augmented the activity and expression of cytochrome c oxidase, a primary photoacceptor molecule in the mitochondrial respiratory chain, and reduced the formation of the DNA adduct 8-hydroxy-2'-deoxyguanosine in kidney. LLLT improved renal function and antioxidant defense capabilities in the kidney of Type I diabetic rats. Thus, 670nm LLLT may be broadly applicable to the amelioration of renal complications induced by diabetes that disrupt antioxidant defense mechanisms. PMID- 20356760 TI - Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: A multicentre pilot study of the French geriatric oncology group (GERICO). AB - BACKGROUND: Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs. METHODS: This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients >=70 years with advanced breast, prostate or lung cancer. RESULTS: Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3-4 toxicities were haematological (17.9%) and gastrointestinal (7.7%). CONCLUSION: In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control. PMID- 20356761 TI - Lymphotoxin-alphabeta heterotrimers are cleaved by metalloproteinases and contribute to synovitis in rheumatoid arthritis. AB - Tumor necrosis factor-superfamily (TNF-SF) members, lymphotoxin (LT)-alpha and LTbeta, are proinflammatory cytokines associated with pathology in rheumatoid arthritis. LTalpha3 homotrimers are secreted, whereas LTalpha(1)beta(2) heterotrimers are expressed on the surface of activated lymphocytes. As many TNF SF members are actively cleaved from cell membranes, we determined whether LTalphabeta heterotrimers are also cleaved, and are biologically active in rheumatoid arthritis (RA) patients. LTalphabeta heterotrimers were detected in culture supernatants from activated human T-helper (Th) 0, Th1, and Th17 cells, together with LTalpha3 and TNFalpha. The heterotimers were actively cleaved from the cell surface by ADAM17 metalloproteinase (MMP) and MMP-8, and cleavage was inhibited by TAPI-1, a TNF-alpha converting enzyme (TACE) inhibitor. Soluble LTalphabeta was detected in serum from both normal donors and RA patients, and was elevated in synovial fluid from RA patients compared to osteoarthritis (OA) patients. Levels of LTalphabeta in RA patient synovial fluid correlated with increased TNFalpha, IL-8, IL-12, IL-1beta, IFN-gamma, and IL-6 cytokines. Moreover, recombinant LTalpha1beta2-induced CXCL1, CXCL2, IL-6, IL-8, VCAM-1, and ICAM-1 from primary synovial fibroblasts isolated from RA patients. Therefore, soluble LTalphabeta in synovial fluid is associated with a proinflammatory cytokine milieu that contributes to synovitis in RA. PMID- 20356762 TI - Asymmetric charge partitioning upon dissociation of DNA duplexes. AB - Upon collisional activation, a series of DNA duplexes exhibited a significant degree of asymmetric dissociation with respect to charge partitioning among the single strands. That is, the charge states of the single strand product ions did not equal q/2 for even precursor charge states or (q + 1)/2 and (q-1)/2 for odd precursor charge states (where q is the charge of the precursor). The factors that affect this asymmetric charge partitioning were assessed. The smaller, lower charged duplexes resulted in more symmetric dissociation compared with larger duplexes in higher charge states, which displayed a high degree of asymmetry upon dissociation. The composition of the duplexes influenced charge partitioning, with those containing a greater number of A/T base pairs showing more symmetric dissociation relative to the more G/C rich duplexes. The use of higher collisional energies resulted in significantly more asymmetric dissociation. Comparisons were made with the dissociation behavior previously studied for protein noncovalent complexes and past studies of the gas-phase conformations and dissociation of DNA complexes. PMID- 20356764 TI - Audio and video recording system for routine documentation of fluoroscopic procedures. AB - Because aviation and other reliable systems routinely record and analyze performance, the authors investigated the feasibility and utility of installing a system capable of recording image-guided procedures. An audio/video recording system adapted from those used in simulation laboratories was installed in a new pediatric interventional radiology suite. In this report, the authors describe the recording system as well as how it can be used to study radiation use during individual procedures. These results illustrate how routinely recording more than 300 procedures during the past 14 months and the detailed analysis of selected recordings can provide insights that lead to continual improvements in performance. PMID- 20356765 TI - Prospects for de-automatization. AB - Research by Raz and his associates has repeatedly found that suggestions for hypnotic agnosia, administered to highly hypnotizable subjects, reduce or even eliminate Stroop interference. The present paper sought unsuccessfully to extend these findings to negative priming in the Stroop task. Nevertheless, the reduction of Stroop interference has broad theoretical implications, both for our understanding of automaticity and for the prospect of de-automatizing cognition in meditation and other altered states of consciousness. PMID- 20356766 TI - PTX3 expression in the heart tissues of patients with myocardial infarction and infectious myocarditis. AB - INTRODUCTION: The long pentraxin 3 is involved in innate resistance to pathogens, controlling inflammation and extracellular matrix remodeling. Moreover, pentraxin 3 plays a nonredundant role in the regulation of cardiac tissue damage in mice and, recently, it has been proposed as a new candidate marker for acute and chronic heart diseases. However, the actual localization and cellular sources of pentraxin 3 in ischemic and infectious cardiac pathology have not been carefully defined. METHODS: In this study, using immunohistochemistry, we analyzed pentraxin 3 expression in the heart tissues of patients with acute myocardial infarction at different time points after the ischemic event. In addition, we studied the heart tissues of patients with infectious myocarditis (fungi, bacteria, and protozoa) and patients who died of noncardiac events with normal heart histology. RESULTS: In acute myocardial infarction cases, we observed pentraxin 3 localized within and around ischemic lesions. On the contrary, no pentraxin 3 was observed in normal heart areas. In early ischemic lesions, pentraxin 3 was localized primarily in granulocytes; in more advanced acute myocardial infarction, pentraxin 3 positivity was found in the interstitium and in the cytoplasm of macrophages and the endothelium, whereas most granulocytes did not express pentraxin 3, presumably as a consequence of degranulation. In infectious myocarditis, pentraxin 3 was present and localized within and around histological lesions, associated with macrophage, endothelial cell, and, more rarely, myocardiocyte and granulocyte positivities. As observed in acute myocardial infarction patients, no pentraxin 3 staining was found in normal heart areas. CONCLUSIONS: Thus, neutrophils are an early source of pentraxin 3 in acute myocardial infarction and presumably other inflammatory heart disorders. Subsequently, in acute myocardial infarction and infectious myocarditis, pentraxin 3 is produced by macrophages, the endothelium, and, to a lesser extent, myocardiocytes, and localized in the interstitium. PMID- 20356763 TI - Whole tumor antigen vaccines. AB - Although cancer vaccines with defined antigens are commonly used, the use of whole tumor cell preparations in tumor immunotherapy is a very promising approach and can obviate some important limitations in vaccine development. Whole tumor cells are a good source of TAAs and can induce simultaneous CTLs and CD4(+) T helper cell activation. We review current approaches to prepare whole tumor cell vaccines, including traditional methods of freeze-thaw lysates, tumor cells treated with ultraviolet irradiation, and RNA electroporation, along with more recent methods to increase tumor cell immunogenicity with HOCl oxidation or infection with replication-incompetent herpes simplex virus. PMID- 20356767 TI - Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population. AB - GABA (gamma-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11+15 A>G (rs2279020) and GABRG2 588C>T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11+15 A>G polymorphism conferred high risk for epilepsy susceptibility at genotype 'AG' (P=0.004, OR=1.77, 95% CI=1.20-2.63), 'GG' (P=0.01, OR=1.80, 95% CI=1.15-2.80) and G allele level (P=0.001, OR=1.50, 95% CI=1.16-1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant 'GG' genotype (P=0.031, OR=1.84, 95% CI=1.05-3.23) and G allele (P=0.020, OR=1.43, 95% CI=1.05-1.95). However GABRG2 588C>T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABA(A) receptor subtypes in epilepsy susceptibility and pharmacotherapy. PMID- 20356768 TI - Technique tip: subtalar joint fusion using a parallel guide and double screw fixation. AB - A wide range of techniques has been described to achieve subtalar (talocalcaneal) arthrodesis using interfragmental screw fixation. In this technical report, we describe a method that enables us to accurately position 2 screws across the subtalar joint in order to achieve arthrodesis between the talus and calcaneus. Careful attention to the tips described in this report should minimize the risk of aberrant placement of the screws while expediting the process of osteosynthesis. PMID- 20356769 TI - Effectiveness of composite bone graft substitute plugs in the treatment of chondral and osteochondral lesions of the talus. AB - A review of outcomes in 13 patients with talar dome osteochondral or chondral lesions treated with a bone graft substitute plug was undertaken in an effort to evaluate its effectiveness in comparison with other reported surgical techniques. Mean patient age was 36.4 (range 16 to 57) years. Mean follow-up was 30.1 (range 7 to 43) months. Medial malleolar osteotomy was performed in 9 (69.23%) cases. Average defect diameter was 9.8 (range 5 to 20) mm. Pain decreased significantly from 6.2 (range 3 to 9) to 4.0 (range 0 to 9) (P = .009). Postoperative American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scores averaged 67.3 (range 26 to 100). Younger age, smaller defect size, and avoidance of medial malleolar osteotomy resulted in better outcomes. Mean Short Form-36 scores for the study group fell below US norms in all categories, and 12 (92.31%) ankles demonstrated persistent lesions radiographically. Postoperative magnetic resonance imaging in 2 (15.39%) patients demonstrated enlarged lesions, and 4 (30.77%) patients underwent revision surgery that revealed abnormal cartilage around the implant site. Complications included 1 (7.69%) deep venous thrombosis, 1 (7.69%) arthrofibrosis, and 1 (7.69%) superficial neuritis. Despite some improvement in pain, comparison of functional outcome showed bone graft substitute plug implantation to be less effective overall than other operative interventions. Future investigations with more specific selection criteria are warranted to gain further insight into the efficacy of these bone graft substitute plugs. PMID- 20356770 TI - A review of tarsal coalition and pes planovalgus: clinical examination, diagnostic imaging, and surgical planning. AB - Pediatric pes planovalgus deformity may be classified as flexible or rigid. The rigid pes planovalgus is often a result of a tarsal coalition, which is typically characterized as a painful unilateral or bilateral deformity, frequently associated with peroneal spasm. However, many tarsal coalitions are asymptomatic and demonstrate no peroneal spasm or pes planovalgus deformity. Likewise, the severe pes planovalgus foot type can demonstrate some of the same clinical and radiographic features of a tarsal coalition, especially in the obese adolescent patient. Also, peroneal spasm may occur in the noncoalesced foot, making diagnosis and etiology more difficult to elucidate. The authors believe that many patients with a pes planovalgus deformity lie in this "gray zone": somewhere between the frank osseous coalition and the flexible pes planovalgus. The "step forward Hubscher maneuver" is introduced as an effective means of evaluating the flexibility of a pes planovalgus foot by negating the effects of a gastrocnemius or gastrocnemius-soleus equinus. This article focuses on the clinical examination and findings of specific imaging studies to assist in an accurate diagnosis of these complicated patients. This will also help to reveal the various surgical options that are appropriate for the individual patient. Emphasis is placed on computerized tomography (CT) imaging and offers enhanced methods for ordering this test to specifically evaluate middle facet coalitions of the subtalar joint. The authors also introduce "lateral tarsal wedging," an image finding associated with severe deformities, the implications of this finding, as well as its impact on surgical planning. PMID- 20356771 TI - Optimal control design of pulse shapes as analytic functions. AB - Representing NMR pulse shapes by analytic functions is widely employed in procedures for optimizing performance. Insights concerning pulse dynamics can be applied to the choice of appropriate functions that target specific performance criteria, focusing the solution search and reducing the space of possible pulse shapes that must be considered to a manageable level. Optimal control theory can accommodate significantly larger parameter spaces and has been able to tackle problems of much larger scope than more traditional optimization methods. However, its numerically generated pulses, as currently constructed, do not readily incorporate the capabilities of particular functional forms, and the pulses are not guaranteed to vary smoothly in time, which can be a problem for faithful implementation on older hardware. An optimal control methodology is derived for generating pulse shapes as simple parameterized functions. It combines the benefits of analytic and numerical protocols in a single powerful algorithm that both complements and enhances existing optimization strategies. PMID- 20356772 TI - 2D binary QSAR modeling of LPA3 receptor antagonism. AB - A structurally diverse dataset of 119 compounds was used to develop and validate a 2D binary QSAR model for the LPA(3) receptor. The binary QSAR model was generated using an activity threshold of greater than 15% inhibition at 10 microM. The overall accuracy of the model on the training set was 82%. It had accuracies of 55% for active and 91% for inactive compounds, respectively. The model was validated using an external test set of 10 compounds. The accuracy on the external test set was 60% overall, identifying three out of seven actives and all three inactive compounds. This model was combined with similarity searching to rapidly screen libraries and select 14 candidate LPA(3) antagonists. Experimental assays confirmed 13 of these (93%) met the 15% inhibition threshold defining actives. The successful application of the model to select candidates for screening demonstrates the power of this binary QSAR model to prioritize compound selection for experimental consideration. PMID- 20356773 TI - Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients. AB - Methylenetetrahydrofolate reductase (MTHFR) is a key enzymatic component of the folate cycle, converting 5,10-methylenetetrahydrofolate into 5 methyltetrahydrofolate, the methyl donor for remethylation of homocysteine into methionine. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life. More than 50 mutations have been reported so far in affected patients but only a few cases with very early onset of symptoms during the first weeks have been described, most of them showing a particular severe clinical course. We detected two novel mutations by direct sequencing of MTHFR in compound heterozygous patients with extremely low or undetectable enzyme activity; one of them had clinical onset during the first week of life and fatal issue at the age of six weeks. Prenatal diagnosis of his sibling allowed for early treatment with B vitamins and betaine and a favorable outcome. One of these mutations (c.523G>A) led to an Ala>Thr transition in the catalytic domain of the enzyme, the other (c.1166G>A) induced alternative splicing of exon 7 at the junction of the catalytic and regulatory domains. Both parents carried only one of these mutations and presented with moderate and intermediate hyperhomocysteinemia, respectively, without neurological symptoms. Severe MTHFR deficiency thus has to be taken into consideration when investigating neurological distress even in the newborn, regarding the need for an earliest possible treatment. Characterization of the relatives further allows for preventive measure to limit the risks of chronic hyperhomocysteinemia. PMID- 20356774 TI - Underquantification of plasma HIV-1 RNA levels in a cohort of newly-diagnosed individuals. PMID- 20356775 TI - Magnetic resonance imaging of Jaccoud's arthropathy in systemic lupus erythematosus. AB - OBJECTIVE: To perform a detailed magnetic resonance imaging (MRI) analysis of the hands of patients with Jaccoud's arthropathy (JA) secondary to systemic lupus erythematosus (SLE). METHODS: The hand with more expressive deformities compatible with JA from a group of SLE patients was examined by 1.5-T MRI. The protocol included coronal, sagittal, and axial turbo-spin-echo images before and after the administration of contrast medium. The presence of synovitis, edema, erosion, cysts, and tenosynovitis in the carpometacarpal, metacarpophalangeal, and proximal interphalangeal joints were scored based on a modified Outcome Measures in Rheumatology recommendations. RESULTS: Twenty SLE patients, (19 women and one man) with median age of 44.7 years (range: 20-76 years), median disease duration of 14.7 years (range: 5-26 years), and median arthritis duration of 13.7 years (range: 4-26 years) were studied. Of the 300 joints evaluated, 202 (67.3%) had some degree of synovitis. Sixteen out of 300 examined joints (5.3%) small areas of erosion were seen in 10 out of the 20 patients (50%). Subchondral bone edema was found in eight out of the 20 (40%) patients or a total of 18 joints (6%). A total of 200 compartments tendons were evaluated, and changes were found in 77 (38.5%) of them. In four out of the 20 patients, the MRI revealed bone cysts. CONCLUSIONS: The MRI seems to be a non-invasive diagnostic tool in patients with JA secondary to SLE, and may contribute to understanding the mechanism involved in the development of this deformity. PMID- 20356776 TI - Clinical spectrum of ankylosing spondylitis in Korea. AB - OBJECTIVES: The aim of this study was to determine the clinical profile of ankylosing spondylitis (AS) in Korea. METHODS: A total of 732 men and 98 women with AS were recruited for the cross-sectional component of the Hanyang University ankylosing spondylitis (HYAS) Study. All participants completed extensive questionnaires about their medical and personal histories, and two rheumatologists concomitantly performed clinical evaluation and previous medical record reviews for all participants. RESULTS: The mean age of onset (SD) was 20.9 (8.1) years. Three hundred and ninety-one patients (47.1%) were found to have a history of peripheral arthritis. Six hundred and four patients (73.9%) were found to have a history of hip joint involvement. Two hundred and thirty-six patients (28.7%) were found to be juvenile-onset AS (JoAS) patients. The frequency of uveitis differed between the sexes (28.2% of men vs 40.8% of women; p=0.03; OR: 1.63; 95% CI: 1.05-2.53). Peripheral arthritis (p<0.001; OR: 4.19; 95% CI: 2.98 5.88) and hip joint involvement (p<0.001; OR: 2.76; 95% CI; 1.77-4.29) were more frequent in JoAS group. HLA-B27 positive cases had a significantly younger age of symptom onset (by 5.3 years), more uveitis, and a higher frequency of hip joint involvement than HLA-B27 negative patients. CONCLUSIONS: The clinical features of our patients are largely similar to those in other studies, with a few noticeable differences: 1) AS patients in Korea have a higher prevalence of peripheral arthritis and hip joint involvement; 2) female patients have more uveitis, and; 3) JoAS is common in our group. PMID- 20356777 TI - Comment on the article by Durmus et al. "Clinical significance of MEFV mutations in ankylosing spondylitis". PMID- 20356778 TI - Heat and mass transfer under an infant radiant warmer--development of a numerical model. AB - The main objectives of this paper are to present a procedure of how to create and set up a model for the physical processes that take place within an infant radiant warmer and to validate that Computational Fluid Dynamics (CFD) can be used to resolve such problems. In this study, the results are obtained for a simplified model, both in terms of the geometry employed and the prescribed boundary conditions. The results were numerically verified in terms of the convergence history, monitor data and the physical correctness. This study shows that the physical situation is unsteady and the results tend to oscillate, almost periodically, around a mean value. The results presented in the paper are found to be in qualitative agreement with the experimental data. This gives us confidence that the techniques employed in this paper are appropriate and form the starting point for the inclusion of more realistic effects, e.g. real shape of the newborn and radiant lamp, heat generated inside the newborn, moisture transport, etc. PMID- 20356779 TI - Airports, localities and disease: representations of global travel during the H1N1 pandemic. AB - During summer 2009, the UK experienced one of the highest incidences of H1N1 infection outside of the Americas and Australia. Building on existing research into biosecurity and the spread of infectious disease via the global airline network, this paper explores the biopolitics of public health in the UK through an in-depth empirical analysis of the representation of H1N1 in UK national and regional newspapers. We uncover new discourses relating to the significance of the airport as a site for control and the ethics of the treatment of the traveller as a potential transmitter of disease. We conclude by highlighting how the global spread of infectious diseases is grounded in particular localities associated with distinctive notions of biosecurity and the traveller. PMID- 20356780 TI - Characteristics of urban parks associated with park use and physical activity: a review of qualitative research. AB - Given that recent literature reviews on physical activity in urban parks deliberately excluded qualitative findings, we reviewed qualitative research on this topic informed by a published classification scheme based on quantitative research. Twenty-one studies met our inclusion criteria. These studies relied mainly on semi-structured interviews with individuals or in focus groups; only five studies involved in situ observation. Our synthesis aligns with previous quantitative research showing that attributes including safety, aesthetics, amenities, maintenance, and proximity are important for encouraging park use. Furthermore, our synthesis of qualitative research suggests that perceptions of the social environment entwine inextricably with perceptions of the physical environment. If so, physical attributes of parks as well as perceptions of these attributes (formed in relation to broader social contexts) may influence physical activity patterns. Both qualitative and quantitative methods provide useful information for interpreting such patterns, and in particular, when designing and assessing interventions intended to improve the amount and intensity of physical activity. PMID- 20356781 TI - Seroprevalence of anti-H5 antibody in rural Cambodia, 2007. AB - BACKGROUND: Since 2005, eight patients with H5N1 infection were laboratory confirmed in Cambodia. Despite the widespread of highly pathogenic avian influenza H5N1 virus and the intense exposure to poultry, there is growing evidence that H5N1 viruses may not be easily transmitted to human. OBJECTIVES: To evaluate the frequency of H5N1 transmission in rural Cambodia, to identify potential risk factors for H5N1 in humans and to explore the extent of asymptomatic and clinically mild illness among humans. STUDY DESIGN: A seroepidemiologic survey was conducted, 9 weeks after the recognition that H5N1 infection caused the death of a 13 years old female in April 2007. Blood specimens were collected from 700 participants for H5N1 serological testing. All participants were interviewed with standardized questionnaire to collect information about poultry exposure. RESULTS: Eighteen (2.6%) of the 700 villagers were tested positive cases for H5N1 antibodies. These 18 individuals were more likely than seronegative participants to report bathing or swimming in the community pond (p=0.04). CONCLUSIONS: The seroprevalence of H5N1 antibodies was higher than previously reported in the other investigations conducted in Cambodia and Thailand. This finding reinforces the overwhelming evidence that the virus continues to circulate widely in settings where human have high exposure to poultry. Our results, provides additional evidence suggesting that bathing or swimming in the community ponds, remains important potential risk factor for H5N1 infection. Both wild birds and domestic poultry have free access to these ponds which are also used for aquaculture through the dumping of poultry feces for fish feeding. PMID- 20356782 TI - How does voluntary movement stop resting tremor? PMID- 20356783 TI - Rheumatic heart disease in indigenous populations. AB - Rates of acute rheumatic fever and chronic rheumatic heart disease in Aboriginal people, Torres Strait Islanders and Maori continue to be unacceptably high. The impact of rheumatic heart disease is inequitable on these populations as compared with other Australians and New Zealanders. The associated cardiac morbidity, including the development of rheumatic valve disease, and cardiomyopathy, with possible sequelae of heart failure, development of atrial fibrillation, systemic embolism, transient ischaemic attacks, strokes, endocarditis, the need for interventions including cardiac surgery, and impaired quality of life, and shortened life expectancy, has major implications for the individual. The adverse health and social effects may significantly limit education and employment opportunities and increase dependency on welfare. Additionally there may be major adverse impacts on family and community life. The costs in financial terms and missed opportunities, including wasted young lives, are substantial. Prevention of acute rheumatic fever is dependent on the timely diagnosis and treatment of sore throats and skin infections in high-risk groups. Both Australia and New Zealand have registries for acute rheumatic fever but paradoxically neither includes all cases of chronic rheumatic heart disease many of whom would benefit from close surveillance and follow-up. In New Zealand and some Australian States there are programs to give secondary prophylaxis with penicillin, but these are not universal. Surgical outcomes for patients with rheumatic valvular disease are better for valve repair than for valve replacement. Special attention to the selection of the appropriate valve surgery and valve choice is required in pregnant women. It may be necessary to have designated surgical units managing Indigenous patients to ensure high rates of surgical repair rather than valve replacement. Surgical guidelines may be helpful. Long-term follow-up of the outcomes of surgery in Indigenous patients with rheumatic heart disease is required. Underpinning these strategies is the need to improve poverty, housing, education and employment. Cultural empathy with mutual trust and respect is essential. Involvement of Indigenous people in decision making, design, and implementation of primary and secondary prevention programs, is mandatory to reduce the unacceptably high rates of rheumatic heart disease. PMID- 20356784 TI - A cost-analysis study of robotic versus conventional mitral valve repair. AB - BACKGROUND: Robotic mitral valve repair has been performed in Australia since 2004. The aim of this study was to perform a cost-analysis of robotic mitral valve repair (MVR) with direct comparison to conventional MVR surgery. METHODS: All isolated MVRs performed within one metropolitan hospital network, between June 2005 and June 2008, were retrospectively compared. Ad hoc cost analysis was conducted. RESULTS: There were 107 robotic and 40 conventional MVRs performed. The post-operative degrees of mitral regurgitation were comparable. Total operating time was 18% longer in robotic compared to conventional (239 min vs. 202 min, p<0.001, 95% CI: 11-27%). In robotic, Intensive Care Unit stay was reduced by 19% (p=0.002, 37 h vs. 45 h), and length of hospital stay was reduced by 26% (p<0.001, 6.47 days vs. 8.76 days). Mean hospital cost, without including capital costs, was not significantly increased (AUD$18,503 vs. AUD$17,880 p=0.176, 95% CI: -282 to 1,530). CONCLUSIONS: Robotic mitral repair can be performed with similar immediate repair success rates as conventional surgery with a shorter recovery time, but a slightly longer operative time. There is no significant increase in cost over conventional surgery. PMID- 20356785 TI - Amiodarone-induced alveolar haemorrhage: a rare complication of a common medication. AB - Amiodarone pulmonary toxicity (APT) is a common and distinctive form of drug induced lung injury. Several patterns have been described and the most common pattern of APT is interstitial pneumonitis. However, amiodarone-induced diffused alveolar haemorrhage is rarely reported. We describe a case of early onset of APT manifested by respiratory distress, haemoptysis, severe hypoxia and bilateral pulmonary infiltrates that was finally diagnosed with amiodarone-induced diffuse alveolar haemorrhage. High suspicion of APT in patients with these non-specific clinical symptoms is needed. Early recognition and treatment are imperative. PMID- 20356786 TI - Cardiac MRI is superior to gated blood pool imaging in the assessment of left ventricular function in patients post-cardiac transplantation. AB - BACKGROUND: Gated Blood Pool Imaging (GBPI) has low inter-test variability compared to echocardiography, and is often used when accurate repeated measurements of left ventricular ejection fraction are required such as in the surveillance of post-transplant patients. The aim of this study was to determine if cardiac MRI (CMR) could replace Gated Blood Pool Imaging for annual assessment of left ventricular (LV) function in the surveillance of patients post-cardiac transplantation. METHODS: Forty-nine patients at various stages of post-cardiac transplantation presenting for annual review underwent LV functional assessment with GBPI and CMR. LV ejection fractions (EF) obtained from the two methods were compared and limits of agreement determined. RESULTS: The mean EF (plus and minus two standard deviations) was 58.3+/-18% for GBPI and 57.6+/-18% for CMR. The two methods were found to provide clinically equivalent results. CONCLUSIONS: Assessment of LVEF with CMR offers comparable values to GBPI in post-heart transplant patients. However, CMR also allows quantitative volumetric analysis of ventricular volumes and assessment of wall motion and valvular function. As is now accepted in native heart assessment, CMR should be considered the "gold standard" for post-transplant volumetric and functional evaluation. CMR offers information over-and-above traditional imaging modalities. PMID- 20356787 TI - Surgical challenges in rheumatic heart disease in the Australian indigenous population. AB - BACKGROUND: Acute rheumatic fever, leading to rheumatic heart disease (RHD), is rare in Australia except amongst Aboriginal and Torres Strait Islander people. METHODS: Cardiac surgical procedures performed at Flinders Medical Centre on patients from the Top End of the Northern Territory from 1993 to 2008 were reviewed. This study compared Indigenous and non-Indigenous patients on short term morbidity and long term survival employing logistic regression and Cox proportional hazard models. We also outline the challenges of managing Aboriginal patients, as our unit services vast areas of northern Australia inhabited by Indigenous people. RESULTS: The total number of patients from the Northern Territory was 835. Amongst the Indigenous patients, there were 235 (55.6%) isolated coronary artery bypass graft procedures, 171 (40.4%) patients underwent isolated valvular surgery (91 mitral and 80 aortic), and 17 (4.0%) underwent combined valvular surgery with coronary artery bypass graft surgery. CONCLUSIONS: Aboriginal patients requiring valve surgery are younger and have greater comorbidity than non-Aboriginal people. Short term surgical results are similar to non-Aboriginal people but long term outcomes appear to be inferior. Age and socioeconomic conditions of Indigenous patients need to be considered. Cultural issues should be understood and acknowledged and surgery better focused around surgical units with appropriate infrastructure. PMID- 20356788 TI - Differences in treatment and management of indigenous and non-indigenous patients presenting with chest pain: results of the Heart Protection Partnership (HPP) study. PMID- 20356789 TI - Environments and cardiometabolic diseases in aboriginal populations. AB - This review establishes the relevance and frames the relationship of environmental factors to cardiometabolic risk factors and disease in Aboriginal populations. Environmental factors operate at the level of communities or populations. They include contextual measures of places and compositional measures of populations which together constitute "risk conditions" affecting individual risk factors. Environmental factors have been implicated by contrasting Aboriginal and non-Aboriginal populations in cardiometabolic risk factors and outcomes, or by geographic contrasts of Aboriginal populations in remote, rural and urban regions. It is unclear whether heterogeneity in contextual or compositional factors between and within Aboriginal populations is associated with heterogeneity in cardiometabolic risk factors and outcomes. Empirical literature that links environmental factors and cardiometabolic outcomes in Aboriginal populations is critically reviewed for three postulated pathways of influence: (1) behaviour; (2) psychosocial factors; and (3) stress response axes. These pathways, represented as interdependent, can explain how and why environments are associated with cardiometabolic outcomes. The need remains, however, to develop a robust quantitative evidence base in cardiometabolic research aimed at enhancing knowledge of the specific environmental factors related to the cardiometabolic health of Aboriginal populations as well as explicating the underlying mechanisms by which environmental risk conditions 'get under the skin'. PMID- 20356790 TI - Improving medication uptake in aboriginal and Torres Strait islander peoples. AB - BACKGROUND: Poor medication adherence is associated with adverse health outcomes. Improving access and adherence to pharmacological therapy is important in achieving optimal health outcomes for Indigenous populations. In spite of the impressive evidence base for cardiovascular pharmacotherapy, strategies for promoting adherence and evidence based practice are less well refined and the challenges for Indigenous populations are more pronounced. AIM: To identify factors impacting on medication adherence in Aboriginal Australians and identify solutions to improve the quality use of medicines. METHOD: The World Health Organization adherence model was used to classify barriers to adherence. Key elements of this model are (1) health care team/health system; (2) socio-economic factors; (3) therapy; (4) patient; and (5) condition related. RESULTS: Entrenched socio-economic differentials aggravate challenges to medication adherence amongst Aboriginal Australians. Initiatives to promote the quality use of medicines, such as the Quality Use of Medicines Maximised for Aboriginal and Torres Strait Islander People (QUMAX) Program, are important strategies to promote adherence. CONCLUSIONS: Medication adherence is a complex issue and addressing modifiable factors is imperative to improve health outcomes. Subsidised access to medications whether living in urban, regional, rural or remote areas is an important strategy in Closing the Gap. PMID- 20356791 TI - Metabolic myopathies: the challenge of new treatments. AB - The recognition of a series of metabolic/enzymatic dysfunction in metabolic myopathies has allowed new therapeutic advances. The most recent ones are enzymatic replacement therapy (ERT) in glycogenosis type II in both the infantile, juvenile and the adult forms, targeted manipulation of diet that has been tried in glycogenosis type II (Pompe disease), type V (McArdle's disease), and in Carnitine palmitoyl transferase 2 (CPT 2) deficiency, a rare disorder of fatty acid oxidation. A well known hypolipidemic drug, bezafibrate, has been tested to stimulate expression of mutated gene for CPT 2, but it may represent a challenge for a series of other fatty acid mitochondrial disorders to restore the capacity for normal long-chain fatty oxidation in muscle. The present review summarizes the most recent clinical achievements that have achieved the interest for an accurate and early diagnosis of these metabolic disorders. PMID- 20356792 TI - The pre-B cell receptor: turning autoreactivity into self-defense. AB - The first step in establishing the antibody repertoire in humans and mice is the rearrangement of immunoglobulin heavy chain (HC) genes in early B lineage cells. These cells then assemble microHCs with surrogate light chains (SLC) into a pre-B cell receptor (pre-BCR). We propose that the pre-BCR has evolved from an ancient autoreactive BCR, since the SLC is an autoreactive entity that binds to the pre BCR itself and to other self-antigens. Abrogation of autoreactivity in the SLC diminishes pre-BCR signaling and impairs the clonal expansion of pre-B cells producing functional microHCs. Since SLC expression is restricted to pre-B cells, the autoreactivity encoded by the pre-BCR can be utilized to pre-select the antibody repertoire, while simultaneously avoiding the formation of autoreactive B lymphocytes. PMID- 20356793 TI - Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution. AB - Most of the steps of lymphopoiesis have been elucidated but contentious issues remain, particularly regarding the identity and function of the earliest lymphoid progenitors that leave the bone marrow and seed the thymus. Hematopoiesis is effectively continuous throughout life, but there is a profound decline in immune function with increasing age, driven by thymus involution and severely curtailed B cell development. A key question is whether defects in bone marrow progenitors, such as reduced differentiation and repopulation potential, are the common denominator. While thymic involution temporally precedes overt HSC functional decline, a logical supposition is that the latter exacerbates the former. This review explores this possible link, and concludes that improving bone marrow function is fundamental to sustained thymic regeneration. PMID- 20356794 TI - Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making. AB - Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. PMID- 20356795 TI - Mycobacterium africanum is not a major cause of human tuberculosis in Cape Town, South Africa. AB - While Mycobacterium africanum is an important cause of TB in several sites in West Africa, its distribution in other African countries is not well documented. In this study, conducted in Cape Town, 1175 isolates yielded 110 unique RFLP patterns; one of each of these 110 strains was tested for genomic deletions characteristic of M. africanum and other atypical members of the Mycobacterium tuberculosis complex. As none of these strains was marked by the deletion of RD9, we conclude that M. africanum and other atypical members of the M. tuberculosis complex are decidedly uncommon in this part of Africa. PMID- 20356796 TI - Cord blood banking and transplantation in 2010. PMID- 20356797 TI - The production of mannan-binding lectin is dependent upon thyroid hormones regardless of the genotype: a cohort study of 95 patients with autoimmune thyroid disorders. AB - Complement mannan-binding lectin (MBL) deficiency is associated with increased susceptibility to infections and autoimmune diseases. Previous studies suggested that the production of MBL is stimulated by thyroid hormones. The aim of our study was to investigate this association in patients with autoimmune thyroid diseases (AITD). Serum levels of MBL and parameters of the thyroid function were determined in 62 patients with Hashimoto's thyroiditis, 33 with Graves' disease and 47 blood donors. Follow-up measurements were performed after 6 to 24 months. MBL2 genotypes were determined using multiplex PCR and compared to 359 healthy Czech individuals. Serum levels of MBL tightly correlated with thyroid hormones, leading to strongly increased MBL levels in hyperthyroidism and decreased levels in hypothyroidism. With normalization of the thyroid function during follow-up, MBL levels decreased or increased respectively. The observed correlations were not due to MBL polymorphisms since the frequency of MBL2 polymorphisms in AITD patients was not different from the general population. We conclude that AITD are not associated with MBL polymorphisms. However, the MBL production is strongly dependent on thyroid function, regardless of the genotype. PMID- 20356798 TI - Foetal pain? AB - The majority of commentary on foetal pain has looked at the maturation of neural pathways to decide a lower age limit for foetal pain. This approach is sensible because there must be a minimal necessary neural development that makes pain possible. Very broadly, it is generally agreed that the minimal necessary neural pathways for pain are in place by 24 weeks gestation. Arguments remain, however, as to the possibility of foetal pain before or after 24 weeks. Some argue that the foetus can feel pain earlier than 24 weeks because pain can be supported by subcortical structures. Others argue that the foetus cannot feel pain at any stage because it is maintained in a state of sedation in the womb and lacks further neural and conceptual development necessary for pain. Much of this argument rests on the definition of terms such as 'wakefulness' and 'pain'. If a behavioural and neural reaction to a noxious stimulus is considered sufficient for pain, then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between foetal pain and pain in the older infant or adult. PMID- 20356799 TI - Has the prevalence of invalidating musculoskeletal pain changed over the last 15 years (1993-2006)? A Spanish population-based survey. AB - The aim of the current study was to estimate the prevalence and time trend of invalidating musculoskeletal pain in the Spanish population and its association with socio-demographic factors, lifestyle habits, self-reported health status, and comorbidity with other diseases analyzing data from 1993-2006 Spanish National Health Surveys (SNHS). We analyzed individualized data taken from the SNHS conducted in 1993 (n = 20,707), 2001 (n = 21,058), 2003 (n = 21,650) and 2006 (n = 29,478). Invalidating musculoskeletal pain was defined as pain suffered from the preceding 2 weeks that decreased main working activity or free-time activity by at least half a day. We analyzed socio-demographic characteristics, self-perceived health status, lifestyle habits, and comorbid conditions using multivariate logistic regression models. Overall, the prevalence of invalidating musculoskeletal pain in Spanish adults was 6.1% (95% CI, 5.7-6.4) in 1993, 7.3% (95% CI, 6.9-7.7) in 2001, 5.5% (95% CI, 5.1-5.9) in 2003 and 6.4% (95% CI 6-6.8) in 2006. The prevalence of invalidating musculoskeletal pain among women was almost twice that of men in every year (P < .05). The multivariate analysis showed that occupational status (unemployed), sleep <8 hours/day and having any accident in the preceding year were significantly associated in both gender with a higher likelihood of suffering from invalidating musculoskeletal pain among Spanish adults. Within men, other predictors of invalidating musculoskeletal pain were to be married and lower educational level, whereas in women were age of 45 64 years old (OR 1.89, 95% CI 1.32-2.7), obesity (OR 1.23, 95% CI 1.06-1.42), a sedentary lifestyle (OR 1.23, 95% CI 1.06-1.42), and presence of comorbid chronic diseases (OR 1.32, 95% CI 1.14-1.53). Further, worse self-reported health status was also related to a greater prevalence of invalidating musculoskeletal pain (OR 6.88, 95% 5.62-8.40 men, OR 7.24, 95% 6.11-8.57 women). Finally, we found that the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001 for both men (OR 1.31, 95% 1.08-1.58) and women (OR 1.19, 95% 1.03-1.39) with no significant increase from the remaining surveys. Our results suggest that invalidating musculoskeletal pain deserves an increased awareness among health professionals. More educational programs which address postural hygiene, physical exercise, and how to prevent obesity and sedentary lifestyle habits should be provided by Public Health Services. PERSPECTIVE: This population-based study indicates that invalidating musculoskeletal pain that reduces main working activity is a public health problem in Spain. The prevalence of invalidating musculoskeletal pain was higher in women than in men and associated to lower income, poor sleeping, worse self-reported health status, and other comorbid conditions. Further, the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001, but remained stable from the last years (2001 to 2006). PMID- 20356800 TI - Spinal levels of nonprotein thiols are related to nociception in mice. AB - Oxidative stress markers are thought to be related to nociception. Because thiolic compounds are important antioxidants, we investigated the relationship between thiols, endogenous or exogenous, and nociception. Systemic or spinal, but not peripheral, administration of the exogenous thiolic compound N-acetyl-L cysteine (NAC) reduced nociception induced by intraplantar capsaicin injection. Moreover, we detected an increase in lipid peroxidation and 3-nitrotyrosine and a decrease in nonprotein thiolic levels in the lumbar spinal cord of capsaicin injected animals. All these effects were prevented by NAC treatment (i.p. and i.t.). Our findings confirm a role for the spinal cord in NAC actions because systemic NAC administration also reduced the nociception trigged by intrathecal injection of capsaicin. Moreover, adjuvant-induced arthritis, but not paw incision, also -decreases nonprotein thiol levels in the spinal cord. Similarly, NAC produced antinociception in adjuvant-treated animals, but not in paw-incised animals. Finally, we investigated the role of endogenous thiol compounds in the nociceptive process administrating buthionine-suphoxamine (BSO), an inhibitor of glutathione-synthesis. Intrathecal BSO treatment decreased nonprotein thiol levels in the spinal cord, as well as induced mechanical allodynia and chemical and thermal hyperalgesia. In conclusion, our results indicate a critical role for nonprotein thiols in nociception at the level of the spinal cord. PERSPECTIVE: The results presented here indicate that the loss of nonprotein thiols in the spinal cord is involved in pain development. Therefore, the administration of thiolic compounds or other strategies allow thiol levels to be maintained and could be a beneficial action in the therapy of painful conditions. PMID- 20356802 TI - Application of peptide nucleic acid towards development of nanobiosensor arrays. AB - Peptide nucleic acid (PNA) is the modified DNA or DNA analogue with a neutral peptide backbone instead of a negatively charged sugar phosphate. PNA exhibits chemical stability, resistant to enzymatic degradation inside living cell, recognizing specific sequences of nucleic acid, formation of stable hybrid complexes like PNA/DNA/PNA triplex, strand invasion, extraordinary thermal stability and ionic strength, and unique hybridization relative to nucleic acids. These unique physicobiochemical properties of PNA enable a new mode of detection, which is a faster and more reliable analytical process and finds applications in the molecular diagnostics and pharmaceutical fields. Besides, a variety of unique characteristic features, PNAs replace DNA as a probe for biomolecular tool in the molecular genetic diagnostics, cytogenetics, and various pharmaceutical potentials as well as for the development of sensors/arrays/chips and many more investigation purposes. This review paper discusses the various current aspects related with PNAs, making a new hot device in the commercial applications like nanobiosensor arrays. PMID- 20356801 TI - Lower-order pain-related constructs are more predictive of cold pressor pain ratings than higher-order personality traits. AB - Pain is a debilitating condition affecting millions each year, yet what predisposes certain individuals to be more sensitive to pain remains relatively unknown. Several psychological factors have been associated with pain perception, but the structural relations between multiple higher- and lower-order constructs and pain are not well understood. Thus, we aimed to examine the associations between pain perception using the cold pressor task (CPT), higher-order personality traits (neuroticism, negative affectivity, trait anxiety, extraversion, positive affectivity, psychoticism), and lower-order pain-related psychological constructs (pain catastrophizing [pre- and post-], fear of pain, anxiety sensitivity, somatosensory amplification, hypochondriasis) in 66 pain free adults. Factor analysis revealed 3 latent psychological variables: pain- or body-sensitivity, negative affect/neuroticism, and positive affect/extraversion. Similarly, pain responses factored into 3 domains: intensity, quality, and tolerance. Regression and correlation analyses demonstrated that: 1) all the lower-order pain constructs (fear, catastrophizing, and hypochondriasis) are related through a single underlying latent factor that is partially related to the higher-order negative-valence personality traits; 2) pain- or body sensitivity was more strongly predictive of pain quality than higher-order traits; and 3) the form of pain assessment is important-only qualitative pain ratings were significantly predicted by the psychological factors. PERSPECTIVE: Consistent with the biopsychosocial model, these results suggest multiple pain related psychological measures likely assess a common underlying factor, which is more predictive of qualitative than intensity pain ratings. This information may be useful for the development and advancement of pain assessments and treatments while considering the multidimensional nature of pain. PMID- 20356804 TI - Depletion of highly abundant proteins in blood plasma by hydrophobic interaction chromatography for proteomic analysis. AB - The proteomic analysis of plasma is extremely complex due to the presence of few highly abundant proteins. These proteins have to be depleted in order to detect low abundance proteins, which are likely to be of biomedical interest. In this work it was investigated the applicability of hydrophobic interaction chromatography (HIC) as a plasma fractionation method prior to two-dimensional gel electrophoresis (2DGE). The average hydrophobicity of the 56 main plasma proteins was calculated. Plasma proteins were classified as low, medium and highly hydrophobic through a cluster analysis. The highly abundant proteins showed a medium hydrophobicity, and therefore a HIC step was designed to deplete them from plasma. HIC performance was assessed by 2DGE, and it was compared to that obtained by a commercial immuno-affinity (IA) column for albumin depletion. Both methods showed similar reproducibility. HIC allowed partially depleting alpha-1-antitrypsin and albumin, and permitted to detect twice the number of spots than IA. Since albumin depletion by HIC was incomplete, it should be further optimized for its use as a complementary or alternative method to IA. PMID- 20356803 TI - Blunt-ended DNA double-strand breaks induced by endonucleases PvuII and EcoRV are poor substrates for repair in Saccharomyces cerevisiae. AB - Most mechanistic studies of repair of DNA double-strand breaks (DSBs) produced by in vivo expression of endonucleases have utilized enzymes that produce cohesive ended DSBs such as HO, I-SceI and EcoRI. We have developed systems for expression of PvuII and EcoRV, nucleases that produce DSBs containing blunt ends, using a modified GAL1 promoter that has reduced basal activity. Expression of PvuII and EcoRV caused growth inhibition and strong cell killing in both haploid and diploid yeast cells. Surprisingly, there was little difference in sensitivities of wildtype cells and mutants defective in homologous recombination, nonhomologous end-joining (NHEJ), or both pathways. Physical analysis using standard and pulsed field gel electrophoresis demonstrated time-dependent breakage of chromosomal DNA within cells. Although ionizing radiation-induced DSBs were largely repaired within 4h, no repair of PvuII-induced breaks could be detected in diploid cells, even after arrest in G2/M. Rare survivors of PvuII expression had an increased frequency of chromosome XII deletions, an indication that a fraction of the induced DSBs could be repaired by an error-prone process. These results indicate that, unlike DSBs with complementary single-stranded DNA overhangs, blunt-ended DSBs in yeast chromosomes are poor substrates for repair by either NHEJ or recombination. PMID- 20356805 TI - Validation of a quantitative assay for human neutrophil peptide-1, -2, and -3 in human plasma and serum by liquid chromatography coupled to tandem mass spectrometry. AB - A quantitative assay for simultaneous measurement of individual human neutrophil peptide-1, -2 and -3 concentrations will aid in exploring the potential of these antimicrobial peptides as biomarkers for various diseases. Therefore, a liquid chromatography-tandem mass spectrometry method has been developed and validated to allow separate quantification of the three human neutrophil peptides in human plasma and serum. Plasma and serum samples (100 microl) were deproteinized by precipitation, followed by chromatographic separation on a Symmetry 300 C18 column (50 mm x 2.1mm I.D., particle size 3.5 microm), using a water-methanol gradient containing 0.25% (v/v) formic acid and human alpha-defensin 5 as internal standard. Tandem mass spectrometric detection was performed on a triple quadrupole mass spectrometer equipped with electrospray ionization. Despite low fragmentation efficiency of the antimicrobial peptides, multiple reaction monitoring was used for detection, though selecting the quaternary charged ions as both precursor and product. The method was linear for concentrations between 5 and 1000 ng/ml with a limit of detection around 3 ng/ml for all peptides. Intra- and inter-assay precisions were 14.8 and 19.1%, respectively, at the lowest measured endogenous concentration (6.4 ng/ml of HNP-1 in plasma), representing the lower limit of quantification of the assay. Recoveries of HNP-1, -2 and -3 from plasma and serum ranged between 85 and 128%. Analysis of serum samples from intensive care patients showed average concentrations of 362, 570 and 143 ng/ml for HNP-1, -2 and -3, respectively. PMID- 20356806 TI - Quantification of monofluoroacetate and monochloroacetate in human urine by isotope dilution liquid chromatography tandem mass spectrometry. AB - The rodenticide monofluoroacetate (MFA) and monochloroacetate (MCA), a chemical intermediate from several chemical syntheses, have been identified as potential agents of chemical terrorism due to their high toxicity. In preparation for response to poisonings and mass exposures, we have developed a quantification method using isotopic dilution to determine MFA and MCA in urine from 50 to 5000 ng/mL. Both analytes were extracted from urine using solid-phase extraction; extraction recoveries were 62% (MFA) and 76% (MCA). The extracts were then separated with isocratic high-performance liquid chromatography and identified using electrospray ionization tandem mass spectrometry, with detection limits of 0.9 and 7.0 ng/mL for MFA and MCA, respectively. Selectivity was established for both analytes with unique chromatographic retention times which were correlated with isotopically labeled internal standards and the use of two mass spectral transitions for each compound. The intra-day variability was less than 5% for both analytes and the inter-day variability was 7% for MFA and 6% for MCA. PMID- 20356807 TI - Rapid confirmatory method for the determination of sixteen synthetic growth promoters and bisphenol A in bovine milk using dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry. AB - A rapid liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-residue method for the simultaneous quantitation and identification of sixteen synthetic growth promoters and bisphenol A in bovine milk has been developed and validated. Sample preparation was straightforward, efficient and economically advantageous. Milk was extracted with acetonitrile followed by phase separation with NaCl. After centrifugation, the extract was purified by dispersive solid-phase extraction with C18 sorbent material. The compounds were analysed by reversed phase LC-MS/MS using both positive and negative ionization and operated in multiple reaction monitoring (MRM) mode, acquiring two diagnostic product ions from each of the chosen precursor ions for unambiguous confirmation. Total chromatographic run time was less than 10 min for each sample. The method was validated at a level of 1 microg L(-1). A wide variety of deuterated internal standards were used to improve method performance. The accuracy and precision of the method were satisfactory for all analytes. The confirmative quantitative liquid chromatographic tandem mass spectrometric (LC-MS/MS) method was validated according to Commission Decision 2002/657/EC. The decision limit (CCalpha) and the detection capability (CCbeta) were found to be below the chosen validation level of 1 microg L(-1) for all compounds. PMID- 20356808 TI - Simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine in human plasma by high-performance liquid chromatography. AB - A simple and sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method has been developed and validated for simultaneous quantification of five local anesthetics in human plasma: procaine, lidocaine, ropivacaine, tetracaine and bupivacaine. In an ice-water bath, 500 microL plasma sample, containing 100 microg/mL neostigmine methylsulfate as anticholinesterase, was spiked with carbamazepine as internal standard and alkalized by sodium hydroxide. Liquid-liquid extraction with ethyl ether was used for plasma sample preparation. The chromatographic separation was achieved on a Kromosil ODS C18 column with a mobile phase consisting of 30 mM potassium dihydrogen phosphate buffer (0.16% triethylamine, pH adjusted to 4.9 with phosphoric acid) and acetonitrile (63/37, v/v). The detection was performed simultaneously at wavelengths of 210 and 290 nm. The chromatographic analysis time was 13 min per sample. The calibration curves of all five analytes were linear between 0.05 and 5.0 microg/mL (r(2) > or = 0.998). Precision ranged from 1.4% to 7.9% and accuracy was between 91.7% and 106.5%. The validated method is applicable for simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine for therapeutic drug monitoring and pharmacokinetic study. PMID- 20356809 TI - Quantitative determination of oxytocin receptor antagonist atosiban in rat plasma by liquid chromatography-tandem mass spectrometry. AB - A kinetic study of atosiban was conducted following repeated intravenous administration in Wistar rats. Sample analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) following full validation of an in-house method. Eptifibatide, a cyclic peptide, was used as an internal standard (IS). The analyte and internal standard were extracted using solid phase extraction (SPE) method. Chromatographic separation was carried out using an ACE C18 5 microm 50 mm x 4.6 mm column with gradient elution. Mass spectrometric detection was performed using TSQ Quantum ultra AM. The lower limit of quantification was 0.01 microg/ml when 100 microl rat plasma was used. Plasma concentrations of atosiban were measured at 0 (pre-dose), 2, 15, 30, 45, 60, 120 min at the dosage levels of 0.125 mg/kg (low dose), 0.250 mg/kg (mid dose), and 0.500 mg/kg (high dose), respectively. Atosiban plasma concentration measured at Day 1 showed mean peak atosiban concentration (C(max)) 0.40, 0.57, 1.95 microg/ml for low, mid and high dose treated animals and mean peak concentration on Day 28 was 0.41, 0.88, 1.31microg/ml on Day 28 for low, mid and high dose treated animals. PMID- 20356810 TI - Observational studies on prescription practices: interpret with caution. PMID- 20356811 TI - A critical comparison of Davis' Principles of Plastic Surgery with Gillies' Plastic Surgery of the face. AB - INTRODUCTION: The second decade of the 20th century saw the publication of two landmark books - John Staige Davis' Plastic Surgery its Principles and Practice published in Philadelphia in 1919 and Major Harold Gillies' Plastic Surgery of the Face published in the United Kingdom early 1920. The aim of this paper is to compare the books critically as scholarly achievements in their time and note their present day relevance. MATERIAL AND METHODS: Copies of both books are available online having been scanned by Google and Microsoft. They were analyzed with Acrobat software for key words. A senior plastic surgeon with over 30 years of clinical experience reviewed both books for current relevance. KEY RESULTS: Davis' book was more comprehensive as it encompassed reconstructive plastic surgery from head to toe while Gillies' book focused on the face. Davis' book contained a bibliography over 2000 references, while Gillies' book had one reference. Despite Davis's title containing the word 'Principles', Gillies' book not only mentioned principles almost five times as often, but almost all of Gillies' principles remain relevant 90 years later. Furthermore, the quality of Gillies' post-operative results are far outshines to Davis'. CONCLUSION: While Davis' book demonstrates his honesty and scholarship, now it is as interesting as a historical curiosity. Gillies' book remains valuable as it shows his originality and the continued relevance of his principles. PMID- 20356812 TI - A review of litigation in plastic surgery in England. Lessons learned. PMID- 20356813 TI - Successful reconstruction of a gunshot segmental defect of the radius with a free vascularised fibular osteocutaneous flap. AB - The use of the vascularised fibular flap for bony reconstruction was first described for the mandible. It has since been used for upper limb bony defects of various aetiologies (congenital, infective, traumatic and neoplastic). Specifically gunshot segmental defects of the upper limb have been reconstructed with vascularised fibular in the humerus and radius, the common indication in these previous cases was delayed reconstruction. We describe a challenging case of a 40-year-old male with a 6.5 cm segmental radial defect caused by gunshot wounds, which was primarily reconstructed using this microvascular technique. The advantages of the vascularised fibular flap and its suitability for this type of reconstructive surgery are discussed. PMID- 20356814 TI - Correction of nipple hypertrophy: Nipple circumcision technique revisited. PMID- 20356815 TI - Patient satisfaction and aesthetic outcomes after ear reconstruction with a Branemark-type, bone-anchored, ear prosthesis: a 16 year review. AB - INTRODUCTION: Reconstruction of the human ear with a bone-anchored prosthesis is a widely accepted alternative when autologous reconstruction is technically impossible or declined by the individual. However, there are relatively few data in the literature documenting patient satisfaction with this form of reconstruction. METHODS: This study examines different aspects of patient satisfaction using an eighteen-point postal questionnaire to measure patient outcomes against a Likert rating scale. The questionnaire was sent to 33 patients who completed prosthetic ear reconstruction over a 16 year period at a specialist plastic surgery unit in the United Kingdom. Medical case notes for these cases were also reviewed. Twenty completed questionnaires were returned. RESULTS: The response rate was 61%. The majority of patients were satisfied with the aesthetics, ease of handling and comfort of the bone-anchored implant and prosthesis. However, the majority of patients was only moderately satisfied or was dissatisfied with this method of reconstruction. Specifically, 15 of the respondents reported skin problems around the abutments of the bone-anchored implant with 10 patients reporting ongoing skin complications. Granulation tissue was the most common skin problem (12 cases) followed by local infection (10 cases). Interestingly, despite the chronic skin problems, most patients indicated that they would undergo the same procedure again or would recommend it to others. DISCUSSION: Our survey shows that patients fitted with a Branemark-type bone anchored implant for ear reconstruction are pleased with the aesthetic appearance but experience multiple, chronic, skin complications and other implant related problems. These affect their satisfaction with this method of reconstruction. Our findings may have significant implications for patients and surgeons considering this form of reconstruction and for the institutions making decisions about funding this treatment. PMID- 20356819 TI - Influenza vaccination in patients with haematologic malignancies: analysis of practices in 200 patients in a single center. AB - GOALS OF WORK: Despite recent studies demonstrating immunogenicity and tolerance of influenza vaccine in patients with haematologic malignancies, practices are still heterogeneous. The aim of this study was to analyse practices and factors influencing vaccination in a single centre, in the light of recent literature data. PATIENTS AND METHODS: Two hundred patients with haematologic malignancies were included and filled out a standardized questionnaire about influenza vaccination. They were observed prospectively during the epidemic season. MAIN RESULTS: Our study revealed a poor uptake of influenza vaccination (vaccinal rate: 25.5%), in particular in patients younger than 65 y and those with no comorbidities. The main reasons for not being vaccinated were: the vaccination was not suggested to patients (53.7%), vaccination was contraindicated by doctors (24.2%), the patient refused it (21.5%). The main reasons for physicians for contraindicating the vaccine were: haematologic malignancy could be worsened by vaccination (33.3%), vaccination could generate illness or asthenia (27.8%), vaccination would not be efficient (16.7%), unknown (22.2%). CONCLUSIONS: We believe that a better knowledge by physicians of tolerance and efficiency of the vaccine could enhance the vaccination coverage. PMID- 20356820 TI - Arabidopsis thaliana ALG3 mutant synthesizes immature oligosaccharides in the ER and accumulates unique N-glycans. AB - The core oligosaccharide Glc(3)Man(9)GlcNAc(2) is assembled by a series of membrane-bound glycosyltransferases as the lipid carrier dolichylpyrophosphate linked glycan in the endoplasmic reticulum (ER). The first step of this assembly pathway on the ER luminal side is mediated by ALG3 (asparagine-linked glycosylation 3), which is a highly conserved reaction among eukaryotic cells. Complementary genetics compared with Saccharomyces cerevisiae ALG gene families and bioinformatic approaches have enabled the identification of ALG3 from other species. In Arabidopsis thaliana, AtALG3 (At2g47760) was identified as alpha1,3 mannosyltransferase. Complementation analysis showed that AtALG3 rescued the temperature-sensitive phenotype, that lipid-linked oligosaccharide assemblies and that protein underglycosylation of S. cerevisiae ALG3-deficient mutant. In Arabidopsis ALG3 mutant, an immature lipid-linked oligosaccharide structure, M5(ER), was synthesized, and used for protein N-glycosylation, resulting in the blockade of subsequent maturation with the concanavalin A affinoactive and Endo H insensitive structure. N-Glycan profiling of total proteins from alg3 mutants exhibited a unique structural profile, alg3 has rare N-glycan structures including Man(3)GlcNAc(2), M4(ER), M5(ER) and GlcM5(ER), which are not usually detected in Arabidopsis, and a much less amount of complex-type N-glycan than that in wild type. Interestingly, despite protein N-glycosylation differences compared with wild type, alg3 showed no obvious phenotype under normal and high temperature or salt/osmotic stress conditions. These results indicate that AtALG3 is a critical factor for mature N-glycosylation of proteins, but not essential for cell viability and growth in Arabidopsis. PMID- 20356818 TI - Case-crossover analysis of air pollution health effects: a systematic review of methodology and application. AB - BACKGROUND: Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context. OBJECTIVE: We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application. DATA SOURCES AND EXTRACTION: A search was made of the MEDLINE and EMBASE databases.Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. DATA SYNTHESIS: The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design's application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO application reports, 13.6% studied effect modification for variables at the individual level. CONCLUSIONS: The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use. PMID- 20356821 TI - FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line. AB - The signaling axis comprising the parathyroid hormone (PTH)-related peptide (PTHrP), the PTH/PTHrP receptor and the fibroblast growth factor receptor 3 (FGFR3) plays a central role in chondrocyte proliferation. The Indian hedgehog (IHH) gene is normally expressed in early hypertrophic chondrocytes, and its negative feedback loop was shown to regulate PTH/PTHrP receptor signaling. In this study, we examined the regulation of PTH/PTHrP receptor gene expression in a FGFR3-transfected chondrocytic cell line, CFK2. Expression of IHH could not be verified on these cells, with consequent absence of hypertrophic differentiation. Also, expression of the PTH/PTHrP receptor (75% reduction of total mRNA) and the PTHrP (50% reduction) genes was reduced in CFK2 cells transfected with FGFR3 cDNA. Interestingly, we verified significant reduction in cell growth and increased apoptosis in the transfected cells. STAT1 was detected in the nuclei of the CFK2 cells transfected with FGFR3 cDNA, indicating predominance of the JAK/STAT signaling pathway. The reduction in PTH/PTHrP receptor gene in CFK2 cells overexpressing FGFR3 was partially blocked by treatment with an inhibitor of JAK3 (WHI-P131), but not with an inhibitor of MAPK (SB203580) or JAK2 (AG490). Altogether, these findings suggest that FGFR3 down-regulates PTH/PTHrP receptor gene expression via the JAK/STAT signaling in chondrocytic cells. PMID- 20356822 TI - Dlk-1, a cell surface antigen on foetal hepatic stem/progenitor cells, is expressed in hepatocellular, colon, pancreas and breast carcinomas at a high frequency. AB - Delta-like 1 protein (Dlk-1), also known as preadipocyte factor 1 (Pref-1), is a transmembrane and secreted protein with epidermal growth factor (EGF)-like repeats. Dlk-1 is known to be expressed in foetal liver, but absent in neonatal and adult liver in mice and rats. Dlk-1 is also expressed in a subpopulation of hepatic oval cells, which are considered as stem/progenitor cells in rat adult liver. In this study, we generated monoclonal antibodies against human Dlk-1 (hDlk-1) and investigated hDlk-1 expression in human liver and hepatocellular carcinoma (HCC). Like rodent livers, hDlk-1 was detected in foetal liver, but not in adult liver. In HCC, hDlk-1 was positive for 20.5% of the cases examined and was localized in both cytoplasm and cell membrane, whereas hDlk-1 was undetected in viral hepatitis, nodular cirrhosis. Interestingly, hDlk-1 positive HCC was found more frequently in younger patients and its expression was correlated with alpha-fetoprotein expression. Furthermore, hDlk-1 was also detected frequently in colon adenocarcinomas (58%), pancreatic islet carcinoma (50%), and small cell lung carcinoma (50%). Thus, hDlk-1 is a cell surface protein expressed in many carcinomas including HCC and may be a potential target for monoclonal antibody therapy for carcinomas. PMID- 20356823 TI - Molecular mechanism of polarized transport. AB - Mechanisms of generation and maintenance of cell polarity have been investigated using various organisms and cell lines. During and after the establishment of cell polarity, polarized (vesicular) transport as well as cell-cell adhesion is essential. Here, I introduce each molecular step of polarized transport and the molecules involved there. Usually, epithelial cells and neurons are two well known examples of polarized cells. Thus, I next describe the similarity and difference in polarized transport between these two cell types. Though closely connected, the relationship between cell-cell adhesion and polarized transport remain poorly understood. I will take a few examples indicating the relationship between them. Finally, I will present the future directions in this field. PMID- 20356824 TI - Interaction of weakly bound antibiotics neomycin and lincomycin with bovine and human serum albumin: biophysical approach. AB - The thermodynamics of interaction of neomycin and lincomycin with bovine serum albumin (BSA) and human serum albumin (HSA) has been studied using isothermal titration calorimetry (ITC), in combination with UV-visible, steady state and time resolved fluorescence spectroscopic measurements. Neomycin is observed to bind weakly to BSA and HSA whereas lincomycin did not show any evidence for binding with the native state of these proteins, rather it interacts in the presence of surfactants. The ITC results suggest 1 : 1 binding stoichiometry for neomycin in the studied temperature range. The values of the van't Hoff enthalpy do not agree with the calorimetric enthalpy in the case of neomycin, suggesting conformational changes in the protein upon ligand binding, as well as with the rise in the temperature. Experiments at different ionic strengths, and in the presence of tetrabutyl ammonium bromide and surfactants suggest the predominant involvement of electrostatic interactions in the complexation process of neomycin with BSA and HSA, and non-specific interaction behaviour of lincomycin with these proteins. PMID- 20356825 TI - Effects of aging, body mass index, plasma lipid profiles, and smoking on human plasma N-glycans. AB - Protein glycosylation affects nearly all molecular interactions at the cell surface and in the intercellular space. Many of the physiological variations which are part of homeostatic mechanisms influence glycosylation. However, a comprehensive overview of changes in glycosylation caused by aging and common lifestyle parameters is still lacking. After analyzing N-glycans in the plasma of 1914 individuals from the Croatian islands of Vis and Korcula, we performed a comprehensive analysis of the dependence of different glycosylation features (position of fucose, level of galactosylation, sialylation and branching) on aging, smoking, body fat and plasma lipid status. A number of statistically significant associations were observed. Glycosylation changes with aging were especially evident in females, mostly in association with the transition from pre menopausal to post-menopausal age. Levels of core-fucosylated, non galactosylated, digalactosylated and disialylated biantennary glycans were shown to be mainly age dependent, but the level of branching and higher levels of galactosylation were found to correlate with lipid status. For the majority of glycans which we analyzed, all examined parameters explained up to 5% of the variance. The only notable exception were non-galactosylated glycans where 20% of the variance was explained mostly by age and blood pressure. In general, only a small fraction of the variability in glycan levels observed in a population was explained by age and other measured parameters, indicating that even in the absence of a genetic template, glycan levels are mostly determined by genetic background and/or specific pathophysiological processes. PMID- 20356826 TI - NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity. AB - Fucoidan is a potent inhibitor of the human complement system whose activity is mediated through interactions with certain proteins belonging to the classical pathway, particularly the protein C4. Branched fucoidan oligosaccharides displayed a higher anticomplementary activity as compared to linear structures. Nuclear magnetic resonance (NMR) characterization of the branched oligosaccharides and saturation transfer difference-NMR experiment of the interaction with the protein C4 allowed the identification of the glycan residues in close contact with the target protein. Transferred nuclear Overhauser effect spectroscopy experiment and molecular modeling of fucoidan oligosaccharides indicated that the presence of side chains reduces the flexibility of the oligosaccharide backbone, which thus adopts a conformation which is very close to the one recognized by the protein C4. Together, these results suggest that branching of fucoidan oligosaccharides, determining their conformational state, has a major impact on their anticomplementary activity. PMID- 20356828 TI - Sustainability, autonomy, and benefits from forest commons. PMID- 20356827 TI - Crystal structure of HLA-DP2 and implications for chronic beryllium disease. AB - Chronic beryllium disease (CBD) is a fibrotic lung disorder caused by beryllium (Be) exposure and is characterized by granulomatous inflammation and the accumulation of Be-responsive CD4(+) T cells in the lung. Genetic susceptibility to CBD has been associated with certain alleles of the MHCII molecule HLA-DP, especially HLA-DPB1*0201 and other alleles that contain a glutamic acid residue at position 69 of the beta-chain (betaGlu69). The HLA-DP alleles that can present Be to T cells match those implicated in the genetic susceptibility, suggesting that the HLA contribution to disease is based on the ability of those molecules to bind and present Be to T cells. The structure of HLA-DP2 and its interaction with Be are unknown. Here, we present the HLA-DP2 structure with its antigen binding groove occupied by a self-peptide derived from the HLA-DR alpha-chain. The most striking feature of the structure is an unusual solvent exposed acidic pocket formed between the peptide backbone and the HLA-DP2 beta-chain alpha-helix and containing three glutamic acids from the beta-chain, including betaGlu69. In the crystal packing, this pocket has been filled with the guanidinium group of an arginine from a neighboring molecule. This positively charged moiety forms an extensive H-bond/salt bridge network with the three glutamic acids, offering a plausible model for how Be-containing complexes might occupy this site. This idea is strengthened by the demonstration that mutation of any of the three glutamic acids in this pocket results in loss of the ability of DP2 to present Be to T cells. PMID- 20356829 TI - Learning induces neurotrophin signaling at hippocampal synapses. AB - Learning-induced trophic activity is thought to be critical for maintaining health of the aging brain. We report here that learning, acting through an unexpected pathway, activates synaptic receptors for one of the brain's primary trophic factors. Unsupervised learning, but not exploratory activity alone, robustly increased the number of postsynaptic densities associated with activated (phosphorylated) forms of BDNF's TrkB receptor in adult rat hippocampus; these increases were blocked by an NMDA receptor antagonist. Similarly, stimulation of hippocampal slices at the learning-related theta frequency increased synaptic TrkB phosphorylation in an NMDA receptor-dependent fashion. Theta burst stimulation, which was more effective in this regard than other stimulation patterns, preferentially engaged NMDA receptors that, in turn, activated Src kinases. Blocking the latter, or scavenging extracellular TrkB ligands, prevented theta-induced TrkB phosphorylation. Thus, synaptic TrkB activation was dependent upon both ligand presentation and postsynaptic signaling cascades. These results show that afferent activity patterns and cellular events involved in memory encoding initiate BDNF signaling through synaptic TrkB, thereby ensuring that learning will trigger neurotrophic support. PMID- 20356830 TI - Scaling of morphogen gradients by an expansion-repression integral feedback control. AB - Despite substantial size variations, proportions of the developing body plan are maintained with a remarkable precision. Little is known about the mechanisms that ensure this adaptation (scaling) of pattern with size. Most models of patterning by morphogen gradients do not support scaling. In contrast, we show that scaling arises naturally in a general feedback topology, in which the range of the morphogen gradient increases with the abundance of some diffusible molecule, whose production, in turn, is repressed by morphogen signaling. We term this mechanism "expansion-repression" and show that it can function within a wide range of biological scenarios. The expansion-repression scaling mechanism is analogous to an integral-feedback controller, a key concept in engineering that is likely to be instrumental also in maintaining biological homeostasis. PMID- 20356831 TI - Binding of p110 retinoblastoma protein inhibits nuclear import of simian virus SV40 large tumor antigen. AB - Nuclear import of the simian virus 40 large tumor antigen (T-ag) is dependent on its nuclear localization signal (NLS) within amino acids 126-132 that is recognized by the importin alpha/beta1 heterodimer, as well as a protein kinase CK2 site at serine 112 upstream of the NLS, which enhances the interaction approximately 50-fold. Here we show for the first time that T-ag nuclear import is negatively regulated by N-terminal sequences (amino acids 102-110), which represent the binding site (BS) for the retinoblastoma (Rb) tumor suppressor protein (p110(Rb)). Quantitative confocal laser scanning microscopic analysis of the transport properties of T-ag constructs with or without Rb binding site mutations in living transfected cells or in a reconstituted nuclear transport system indicates that the presence of the RbBS significantly reduces nuclear accumulation of T-ag. A number of approaches, including the analysis of T-ag nuclear import in an isogenic cell pair with and without functional p110(Rb) implicate p110(Rb) binding as being responsible for the reduced nuclear accumulation, with the Ser(106) phosphorylation site within the RbBS appearing to enhance the inhibitory effect. Immunoprecipitation experiments confirmed association of T-ag and p110(Rb) and dependence thereof on negative charge at Ser(106). The involvement of p110(Rb) in modulating T-ag nuclear transport has implications for the regulation of nuclear import of other proteins from viruses of medical significance that interact with p110(Rb), and how this may relate to transformation. PMID- 20356832 TI - Conservation of a glycine-rich region in the prion protein is required for uptake of prion infectivity. AB - Prion diseases are associated with the misfolding of the endogenously expressed prion protein (designated PrP(C)) into an abnormal isoform (PrP(Sc)) that has infectious properties. The hydrophobic domain of PrP(C) is highly conserved and contains a series of glycine residues that show perfect conservation among all species, strongly suggesting it has functional and evolutionary significance. These glycine residues appear to form repeats of the GXXXG protein-protein interaction motif (two glycines separated by any three residues); the retention of these residues is significant and presumably relates to the functionality of PrP(C). Mutagenesis studies demonstrate that minor alterations to this highly conserved region of PrP(C) drastically affect the ability of cells to uptake and replicate prion infection in both cell and animal bioassay. The localization and processing of mutant PrP(C) are not affected, although in vitro and in vivo studies demonstrate that this region is not essential for interaction with PrP(Sc), suggesting these residues provide conformational flexibility. These data suggest that this region of PrP(C) is critical in the misfolding process and could serve as a novel, species-independent target for prion disease therapeutics. PMID- 20356834 TI - The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion. AB - Glucose-stimulated insulin secretion from pancreatic islet beta-cells is dependent in part on pyruvate cycling through the pyruvate/isocitrate pathway, which generates cytosolic alpha-ketoglutarate, also known as 2-oxoglutarate (2OG). Here, we have investigated if mitochondrial transport of 2OG through the 2 oxoglutarate carrier (OGC) participates in control of nutrient-stimulated insulin secretion. Suppression of OGC in clonal pancreatic beta-cells (832/13 cells) and isolated rat islets by adenovirus-mediated delivery of small interfering RNA significantly decreased glucose-stimulated insulin secretion. OGC suppression also reduced insulin secretion in response to glutamine plus the glutamate dehydrogenase activator 2-amino-2-norbornane carboxylic acid. Nutrient-stimulated increases in glucose usage, glucose oxidation, glutamine oxidation, or ATP:ADP ratio were not affected by OGC knockdown, whereas suppression of OGC resulted in a significant decrease in the NADPH:NADP(+) ratio during stimulation with glucose but not glutamine + 2-amino-2-norbornane carboxylic acid. Finally, OGC suppression reduced insulin secretion in response to a membrane-permeant 2OG analog, dimethyl-2OG. These data reveal that the OGC is part of a mechanism of fuel-stimulated insulin secretion that is common to glucose, amino acid, and organic acid secretagogues, involving flux through the pyruvate/isocitrate cycling pathway. Although the components of this pathway must remain intact for appropriate stimulus-secretion coupling, production of NADPH does not appear to be the universal second messenger signal generated by these reactions. PMID- 20356833 TI - Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo. AB - Alpha-synuclein (a-Syn), a protein implicated in Parkinson disease, contributes significantly to dopamine metabolism. a-Syn binding inhibits the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Phosphorylation of TH stimulates its activity, an effect that is reversed by protein phosphatase 2A (PP2A). In cells, a-Syn overexpression activates PP2A. Here we demonstrate that a-Syn significantly inhibited TH activity in vitro and in vivo and that phosphorylation of a-Syn serine 129 (Ser-129) modulated this effect. In MN9D cells, a-Syn overexpression reduced TH serine 19 phosphorylation (Ser(P)-19). In dopaminergic tissues from mice overexpressing human a-Syn in catecholamine neurons only, TH-Ser-19 and TH-Ser-40 phosphorylation and activity were also reduced, whereas PP2A was more active. Cerebellum, which lacks excess a Syn, had PP2A activity identical to controls. Conversely, a-Syn knock-out mice had elevated TH-Ser-19 phosphorylation and activity and less active PP2A in dopaminergic tissues. Using an a-Syn Ser-129 dephosphorylation mimic, with serine mutated to alanine, TH was more inhibited, whereas PP2A was more active in vitro and in vivo. Phosphorylation of a-Syn Ser-129 by Polo-like-kinase 2 in vitro reduced the ability of a-Syn to inhibit TH or activate PP2A, identifying a novel regulatory role for Ser-129 on a-Syn. These findings extend our understanding of normal a-Syn biology and have implications for the dopamine dysfunction of Parkinson disease. PMID- 20356835 TI - Phosphorylation of histone H2A.X by DNA-dependent protein kinase is not affected by core histone acetylation, but it alters nucleosome stability and histone H1 binding. AB - Phosphorylation of the C-terminal end of histone H2A.X is the most characterized histone post-translational modification in DNA double-stranded breaks (DSB). DNA dependent protein kinase (DNA-PK) is one of the three phosphatidylinositol 3 kinase-like family of kinase members that is known to phosphorylate histone H2A.X during DNA DSB repair. There is a growing body of evidence supporting a role for histone acetylation in DNA DSB repair, but the mechanism or the causative relation remains largely unknown. Using bacterially expressed recombinant mutants and stably and transiently transfected cell lines, we find that DNA-PK can phosphorylate Thr-136 in addition to Ser-139 both in vitro and in vivo. Furthermore, the phosphorylation reaction is not inhibited by the presence of H1, which in itself is a substrate of the reaction. We also show that, in contrast to previous reports, the ability of the enzyme to phosphorylate these residues is not affected by the extent of acetylation of the core histones. In vitro assembled nucleosomes and HeLa S3 native oligonucleosomes consisting of non acetylated and acetylated histones are equally phosphorylated by DNA-PK. We demonstrate that the apparent differences in the extent of phosphorylation previously observed can be accounted for by the differential chromatin solubility under the MgCl(2) concentrations required for the phosphorylation reaction in vitro. Finally, we show that although H2A.X does not affect nucleosome conformation, it has a de-stabilizing effect that is enhanced by the DNA-PK mediated phosphorylation and results in an impaired histone H1 binding. PMID- 20356836 TI - Akt2 modulates glucose availability and downstream apoptotic pathways during development. AB - Glucose is the primary energy substrate for eukaryotic cells and the predominant substrate for the brain. Studies suggest that glucose serves an additional role in the regulation of cellular functions, including viability. Zebrafish is a tractable system for defining the cellular and molecular mechanisms perturbed by impaired glucose transport and metabolism. Previously, we demonstrated a critical role for the facilitative glucose transporter, Glut1, in the regulation of embryonic brain development. In this study, we aim to identify mediators in this Glut1-sensitive process by investigating the role of the antiapoptotic kinase, Akt2. Results show that abrogating expression of akt2 causes a phenotype strikingly similar to that observed when glut1 expression is inhibited. akt2 deficient embryos exhibit increased neuronal apoptosis, impaired glucose uptake, and death by 72 h postfertilization. Similar to what was observed in the glut1 morphants, inhibiting the expression of the proapoptotic protein, bad, in the context of impaired akt2 expression results in the inhibition of apoptosis and rescue of the morphant embryos. Intriguingly, overexpression of glut1 in the akt2 morphants was also able to rescue these embryos. Quantitative reverse transcription-PCR analysis revealed decreased glut1 transcript expression in akt2 morphant embryos. Taken together, these data suggest that Akt2 modulates glucose availability by regulating Glut1 expression at the transcript level. These data support a role for akt2 in an integrative pathway directly linking glucose, Glut1 expression, and activation of apoptosis and demonstrate the dependence of akt2 on glucose availability for the maintenance of cellular viability, particularly in the central nervous system. PMID- 20356837 TI - Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology. AB - Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands. These compounds produced a spectrum of activities in each assay ranging from 0 to 100% of maximal response. By testing different classes of compounds in ovariectomized rats, we established that ligands that transactivated a model promoter 40-80% of an agonist, recruited the coactivator GRIP-1 <15%, and stabilized the N-/C-terminal interdomain interaction <7% induced bone formation with reduced effects in the uterus and in sebaceous glands. Using these criteria, multiple SARMs were synthesized including MK-0773, a 4-aza-steroid that exhibited tissue selectivity in humans. Thus, AR activated to moderate levels due to reduced cofactor recruitment, and N-/C-terminal interactions produce a fully anabolic response, whereas more complete receptor activation is required for reproductive effects. This bimodal activation provides a molecular basis for the development of SARMs. PMID- 20356838 TI - Mouse Dfa is a repressor of TATA-box promoters and interacts with the Abt1 activator of basal transcription. AB - Our study of the mouse Ate1 arginyltransferase, a component of the N-end rule pathway, has shown that Ate1 pre-mRNA is produced from a bidirectional promoter that also expresses, in the opposite direction, a previously uncharacterized gene (Hu, R. G., Brower, C. S., Wang, H., Davydov, I. V., Sheng, J., Zhou, J., Kwon, Y. T., and Varshavsky, A. (2006) J. Biol. Chem. 281, 32559-32573). In this work, we began analyzing this gene, termed Dfa (divergent from Ate1). Mouse Dfa was found to be transcribed from both the bidirectional P(Ate1/Dfa) promoter and other nearby promoters. The resulting transcripts are alternatively spliced, yielding a complex set of Dfa mRNAs that are present largely, although not exclusively, in the testis. A specific Dfa mRNA encodes, via its 3'-terminal exon, a 217-residue protein termed Dfa(A). Other Dfa mRNAs also contain this exon. Dfa(A) is sequelogous (similar in sequence) to a region of the human/mouse HTEX4 protein, whose physiological function is unknown. We produced an affinity purified antibody to recombinant mouse Dfa(A) that detected a 35-kDa protein in the mouse testis and in several cell lines. Experiments in which RNA interference was used to down-regulate Dfa indicated that the 35-kDa protein was indeed Dfa(A). Furthermore, Dfa(A) was present in the interchromatin granule clusters and was also found to bind to the Ggnbp1 gametogenetin-binding protein-1 and to the Abt1 activator of basal transcription that interacts with the TATA-binding protein. Given these results, RNA interference was used to probe the influence of Dfa levels in luciferase reporter assays. We found that Dfa(A) acts as a repressor of TATA-box transcriptional promoters. PMID- 20356839 TI - Mechanism of eIF6-mediated inhibition of ribosomal subunit joining. AB - During the process of ribosomal assembly, the essential eukaryotic translation initiation factor 6 (eIF6) is known to act as a ribosomal anti-association factor. However, a molecular understanding of the anti-association activity of eIF6 is still missing. Here we present the cryo-electron microscopy reconstruction of a complex of the large ribosomal subunit with eukaryotic eIF6 from Saccharomyces cerevisiae. The structure reveals that the eIF6 binding site involves mainly rpL23 (L14p in Escherichia coli). Based on our structural data, we propose that the mechanism of the anti-association activity of eIF6 is based on steric hindrance of intersubunit bridge formation around the dynamic bridge B6. PMID- 20356840 TI - Structural analysis of Thermus thermophilus HB27 mannosyl-3-phosphoglycerate synthase provides evidence for a second catalytic metal ion and new insight into the retaining mechanism of glycosyltransferases. AB - Mannosyl-3-phosphoglycerate synthase is a glycosyltransferase involved in the two step synthetic pathway of mannosylglycerate, a compatible solute that accumulates in response to salt and/or heat stresses in many microorganisms thriving in hot environments. The three-dimensional structure of mannosyl-3-phosphoglycerate synthase from Thermus thermophilus HB27 in its binary complex form, with GDP alpha-D-mannose and Mg(2+), shows a second metal binding site, about 6 A away from the mannose moiety. Kinetic and mutagenesis studies have shown that this metal site plays a role in catalysis. Additionally, Asp(167) in the DXD motif is found within van der Waals contact distance of the C1' atom in the mannopyranose ring, suggesting its action as a catalytic nucleophile, either in the formation of a glycosyl-enzyme intermediate according to the double-displacement S(N)2 reaction mechanism or in the stabilization of the oxocarbenium ion-like intermediate according to the D(N)*A(Nss) (S(N)i-like) reaction mechanism. We propose that either mechanism may occur in retaining glycosyltransferases with a GT-A fold, and, based on the gathered structural information, we identified an extended structural signature toward a common scaffold between the inverting and retaining glycosyltransferases. PMID- 20356841 TI - Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex. AB - Protein kinase A (PKA) activation by cAMP phosphorylates multiple target proteins in numerous platelet inhibitory pathways that have a very important role in maintaining circulating platelets in a resting state. Here we show that in thrombin- and collagen-stimulated platelets, PKA is activated by cAMP-independent mechanisms involving dissociation of the catalytic subunit of PKA (PKAc) from an NFkappaB-IkappaBalpha-PKAc complex. We demonstrate mRNA and protein expression for most of the NFkappaB family members in platelets. From resting platelets, PKAc was co-immunoprecipitated with IkappaBalpha, and conversely, IkappaBalpha was also co-immunoprecipitated with PKAc. This interaction was significantly reduced in thrombin- and collagen-stimulated platelets. Stimulation of platelets with thrombin- or collagen-activated IKK, at least partly by PI3 kinase-dependent pathways, leading to phosphorylation of IkappaBalpha, disruption of an IkappaBalpha-PKAc complex, and release of free, active PKAc, which phosphorylated VASP and other PKA substrates. IKK inhibitor inhibited thrombin-stimulated IkBalpha phosphorylation, PKA-IkBalpha dissociation, and VASP phosphorylation, and potentiated integrin alphaIIbbeta3 activation and the early phase of platelet aggregation. We conclude that thrombin and collagen not only cause platelet activation but also appear to fine-tune this response by initiating downstream NFkappaB-dependent PKAc activation, as a novel feedback inhibitory signaling mechanism for preventing undesired platelet activation. PMID- 20356842 TI - Differences in the structure and dynamics of the apo- and palmitate-ligated forms of Aedes aegypti sterol carrier protein 2 (AeSCP-2). AB - Sterol carrier protein-2 (SCP-2) is a nonspecific lipid-binding protein expressed ubiquitously in most organisms. Knockdown of SCP-2 expression in mosquitoes has been shown to result in high mortality in developing adults and significantly lowered fertility. Thus, it is of interest to determine the structure of mosquito SCP-2 and to identify its mechanism of lipid binding. We report here high quality three-dimensional solution structures of SCP-2 from Aedes aegypti determined by NMR spectroscopy in its ligand-free state (AeSCP-2) and in complex with palmitate. Both structures have a similar mixed alpha/beta fold consisting of a five-stranded beta-sheet and four alpha-helices arranged on one side of the beta sheet. Ligand-free AeSCP-2 exhibited regions of structural heterogeneity, as evidenced by multiple two-dimensional (15)N heteronuclear single-quantum coherence peaks for certain amino acids; this heterogeneity disappeared upon complex formation with palmitate. The binding of palmitate to AeSCP-2 was found to decrease the backbone mobility of the protein but not to alter its secondary structure. Complex formation is accompanied by chemical shift differences and a loss of mobility for residues in the loop between helix alphaI and strand betaA. The structural differences between the alphaI and betaA of the mosquito and the vertebrate SCP-2s may explain the differential specificity (insect versus vertebrate) of chemical inhibitors of the mosquito SCP-2. PMID- 20356843 TI - FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase. AB - The isomerization of all-trans retinol (vitamin A) to 11-cis retinol in the retinal pigment epithelium (RPE) is a key step in the visual process for the regeneration of the visual pigment chromophore, 11-cis retinal. LRAT and RPE65 are recognized as the minimal isomerase catalytic components. However, regulators of this rate-limiting step are not fully identified and could account for the phenotypic variability associated with inherited retinal degeneration (RD) caused by mutations in the RPE65 gene. To identify new RPE65 partners, we screened a porcine RPE mRNA library using a yeast two-hybrid assay with full-length human RPE65. One identified clone (here named FATP1c), containing the cytosolic C terminal sequence from the fatty acid transport protein 1 (FATP1 or SLC27A1, solute carrier family 27 member 1), was demonstrated to interact dose-dependently with the native RPE65 and with LRAT. Furthermore, these interacting proteins colocalize in the RPE. Cellular reconstitution of human interacting proteins shows that FATP1 markedly inhibits 11-cis retinol production by acting on the production of all-trans retinyl esters and the isomerase activity of RPE65. The identification of this new visual cycle inhibitory component in RPE may contribute to further understanding of retinal pathogenesis. PMID- 20356844 TI - Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. AB - Human maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) are small intestinal enzymes that work concurrently to hydrolyze the mixture of linear alpha-1,4- and branched alpha-1,6-oligosaccharide substrates that typically make up terminal starch digestion products. MGAM and SI are each composed of duplicated catalytic domains, N- and C-terminal, which display overlapping substrate specificities. The N-terminal catalytic domain of human MGAM (ntMGAM) has a preference for short linear alpha-1,4-oligosaccharides, whereas N-terminal SI (ntSI) has a broader specificity for both alpha-1,4- and alpha-1,6 oligosaccharides. Here we present the crystal structure of the human ntSI, in apo form to 3.2 A and in complex with the inhibitor kotalanol to 2.15 A resolution. Structural comparison with the previously solved structure of ntMGAM reveals key active site differences in ntSI, including a narrow hydrophobic +1 subsite, which may account for its additional substrate specificity for alpha-1,6 substrates. PMID- 20356845 TI - Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. AB - The Kruppel-like factor 4 (KLF4) is a transcriptional regulator of proliferation and differentiation in epithelial cells, both during development and tumorigenesis. Although KLF4 functions as a tumor suppressor in several tissues, including the colon, the role of KLF4 in breast cancer is less clear. Here, we show that KLF4 is necessary for maintenance of the epithelial phenotype in non transformed MCF-10A mammary epithelial cells. KLF4 silencing led to alterations in epithelial cell morphology and migration, indicative of an epithelial-to mesenchymal transition. Consistent with these changes, decreased levels of KLF4 also resulted in the loss of E-cadherin protein and mRNA. Promoter/reporter analyses revealed decreased E-cadherin promoter activity with KLF4 silencing, while chromatin immunoprecipitation identified endogenous KLF4 binding to the GC rich/E-box region of this promoter. Furthermore, forced expression of KLF4 in the highly metastatic MDA-MB-231 breast tumor cell line was sufficient to restore E cadherin expression and suppress migration and invasion. These findings identify E-cadherin as a novel transcriptional target of KLF4. The clear requirement for KLF4 to maintain E-cadherin expression and prevent epithelial-to-mesenchymal transition in mammary epithelial cells supports a metastasis suppressive role for KLF4 in breast cancer. PMID- 20356846 TI - Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding. AB - Cellular inhibitor of apoptosis (cIAP) proteins, cIAP1 and cIAP2, are important regulators of tumor necrosis factor (TNF) superfamily (SF) signaling and are amplified in a number of tumor types. They are targeted by IAP antagonist compounds that are undergoing clinical trials. IAP antagonist compounds trigger cIAP autoubiquitylation and degradation. The TNFSF member TWEAK induces lysosomal degradation of TRAF2 and cIAPs, leading to elevated NIK levels and activation of non-canonical NF-kappaB. To investigate the role of the ubiquitin ligase RING domain of cIAP1 in these pathways, we used cIAP-deleted cells reconstituted with cIAP1 point mutants designed to interfere with the ability of the RING to dimerize or to interact with E2 enzymes. We show that RING dimerization and E2 binding are required for IAP antagonists to induce cIAP1 degradation and protect cells from TNF-induced cell death. The RING functions of cIAP1 are required for full TNF-induced activation of NF-kappaB, however, delayed activation of NF kappaB still occurs in cIAP1 and -2 double knock-out cells. The RING functions of cIAP1 are also required to prevent constitutive activation of non-canonical NF kappaB by targeting NIK for proteasomal degradation. However, in cIAP double knock-out cells TWEAK was still able to increase NIK levels demonstrating that NIK can be regulated by cIAP-independent pathways. Finally we show that, unlike IAP antagonists, TWEAK was able to induce degradation of cIAP1 RING mutants. These results emphasize the critical importance of the RING of cIAP1 in many signaling scenarios, but also demonstrate that in some pathways RING functions are not required. PMID- 20356849 TI - Medication-induced hypophosphatemia: a review. AB - Hypophosphatemia (serum phosphorus concentration <2.5 mg/dl, 0.8 mmol/l), although rare in the general population, is commonly observed in hospitalized patients and may be associated with drug therapy. In fact, hypophosphatemia frequently develops in the course of treatment with drugs used in every-day clinical practice including diuretics and bisphosphonates. Proper diagnostic approach of patients with low serum phosphorus concentrations should involve a detailed medical history with special attention to the recent use of medications. The clinical manifestations of drug-induced hypophosphatemia are usually mild but might also be severe and potentially life-threatening. This review aims at a thorough understanding of the underlying pathophysiological mechanisms and risk factors of drug therapy-related hypophosphatemia thus allowing prevention and effective intervention strategies. PMID- 20356848 TI - Aspirin resistance determined from a bed-side test in patients suspected to have acute coronary syndrome portends a worse 6 months outcome. AB - BACKGROUND: Coronary patients resistant to aspirin may have increased risk for ischemic events. Little data were available for patients presenting acutely with chest pain. METHODS AND RESULTS: We used the VerifyNow Aspirin to determine aspirin responsiveness of 314 patients regularly taking aspirin 75-300 mg daily for >or=4 weeks who presented with suspected acute coronary syndrome in Emergency Department. Aspirin resistance was defined as an aspirin reaction unit (ARU) >or=550, and the clinical team was blinded to the ARU reading. The pre-specified study endpoints were the diagnosis of acute myocardial infarction (AMI) for the index admission and major adverse cardiac events including cardiovascular death or recurrent acute coronary syndrome requiring hospitalization within 6 months. Aspirin resistance was noted in 30 (9.6%) patients. There was no difference in the diagnosis of AMI for the index presentation (3/30, 10% vs. 25/284, 8.8%, P = 0.91). Among the 312 hospital survivors, aspirin resistant patients had increased adverse events over 6 months with an overall hazard ratio of 10.0 [95% confidence interval (CI) 4.6-22.0]. After adjusted for elevated Troponin-T, the only confounder in the model, the hazard ratio was 11.1 (95% CI 4.7-26.0). Results were similar in patients treated only medically without revascularization (adjusted hazard ratio 12.1, 95% CI 4.7-26.4). The increased events were observed both from discharge to 30 days and from 30 days to 6 months. CONCLUSION: Aspirin resistance occurs in approximately 10% of patients presenting with suspected acute coronary syndrome and is associated with adverse cardiac events. PMID- 20356847 TI - The plastic energy landscape of protein folding: a triangular folding mechanism with an equilibrium intermediate for a small protein domain. AB - Protein domains usually fold without or with only transiently populated intermediates, possibly to avoid misfolding, which could result in amyloidogenic disease. Whether observed intermediates are productive and obligatory species on the folding reaction pathway or dispensable by-products is a matter of debate. Here, we solved the crystal structure of a small protein domain, SAP97 PDZ2 I342W C378A, and determined its folding pathway. The presence of a folding intermediate was demonstrated both by single and double-mixing kinetic experiments using urea induced (un)folding as well as ligand-induced folding. This protein domain was found to fold via a triangular scheme, where the folding intermediate could be either on- or off-pathway, depending on the experimental conditions. Furthermore, we found that the intermediate was present at equilibrium, which is rarely seen in folding reactions of small protein domains. The folding mechanism observed here illustrates the roughness and plasticity of the protein folding energy landscape, where several routes may be employed to reach the native state. The results also reconcile the folding mechanisms of topological variants within the PDZ domain family. PMID- 20356850 TI - Scrotum balloon: an unusual presentation of emphysematous pyelonephritis. PMID- 20356851 TI - Modern progress in hepatic encephalopathy. PMID- 20356852 TI - Prenatal paracetamol exposure and asthma: further evidence against confounding. AB - BACKGROUND: Observational studies have reported an association between maternal use of paracetamol in pregnancy and childhood asthma, which was not explained by measured confounding factors. However, it is possible that this relation might be confounded by unmeasured behavioural factors linked to paracetamol usage; if that were the case, effects of similar magnitude of partner's paracetamol use and/or postnatal maternal use would be expected. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort, we compared the univariate effects of maternal use of paracetamol in pregnancy on risk of doctor-diagnosed asthma, wheeze and elevated immunoglobulin E (IgE) in the offspring at 7 years of age, with the univariate effects of partner's use and postnatal maternal use on these phenotypes. RESULTS: Maternal use of paracetamol in pregnancy was strongly associated with all outcomes. Partner's use was very weakly associated with asthma but not associated with wheezing or IgE. Postnatal maternal use was associated with asthma and wheezing, though less strongly than was prenatal use, and was not associated with IgE. On mutual adjustment, the effects of maternal use in pregnancy on all outcomes were not substantially attenuated, whereas the effects of partner's use on asthma, and of postnatal maternal use on asthma and wheezing, were reduced. CONCLUSIONS: These findings suggest that the relation between maternal use of paracetamol in pregnancy and childhood asthma is unlikely to be confounded by unmeasured behavioural factors linked to paracetamol use. PMID- 20356853 TI - Automated specimen search in cryo-TEM observation with DIFF-defocus imaging. AB - We have developed an automated specimen search algorithm for cryo-electron microscopy imaging of ice-embedded single particles suspended across regularly spaced holes. To maximize the particle visibility under a low electron exposure rate condition, specimen searching is carried out in diffraction mode. However, images in diffraction mode contain significant pincushion distortion, making it difficult to computationally predict the locations of the regularly spaced holes. We have implemented a distortion-correction mechanism to restore the primitive distortion-free image and a correlation-based algorithm to accurately determine the periodicity of the holes. A stage-shift method to optimize positional reproducibility is also implemented. Addition of our algorithms to the JADAS software for automated transmission electron microscopy data acquisition has significantly improved the accuracy of specimen search. PMID- 20356854 TI - PINK1-linked parkinsonism is associated with Lewy body pathology. AB - Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed the coding region of phosphatase and tensin homolog induced putative kinase 1 gene in a large Spanish family with six members with parkinsonism. The phenotype was characterized by an early-onset (mean: 31.6, standard deviation: 9.6 years, range: 14-45 years), slowly progressive levodopa responsive parkinsonism, initial gait impairment and psychiatric symptoms. We identified two segregating pathogenic phosphatase and tensin homolog-induced putative kinase 1 mutations that were either in homozygous or heterozygous compound state in all affected family members. We found an exon 7 deletion (g.16089_16383del293; c.1252_1488del) and a novel+1U1-dependent 5' splice-site mutation in exon 7 (g.16378G>A; c.1488+1G>A). Leukocyte-derived messenger RNA analysis showed that both mutations caused exon 7 skipping and c.1488+1G>A also lead to an in-frame transcript with a 33 base-pair deletion (p.L485_R497del) resulting from activation of a 5' cryptic exon 7 splice site. Single photon emission computed tomography quantification of striatal dopamine transporter binding (123I-Ioflupane) revealed a posterior-anterior gradient similar to that of idiopathic Parkinson's disease, but there was no correlation between striatal reduced uptake and disease duration. Post-mortem neuropathological examination of an early-onset Parkinson's disease carrier of two heterozygous compound phosphatase and tensin homolog-induced putative kinase 1 mutations showed neuronal loss in the substantia nigra pars compacta, Lewy bodies and aberrant neurites in the reticular nuclei of the brainstem, substantia nigra pars compacta and Meynert nucleus, but the locus ceruleus and the amygdala were spared. This is the first neuropathological report of the brain from an early-onset phosphatase and tensin homolog-induced putative kinase 1-linked parkinsonism showing that mutated phosphatase and tensin homolog-induced putative kinase 1 protein induces Lewy body pathology. Unbalanced preservation of the locus ceruleus may well play a role in the slow evolution of motor symptoms and, probably, in the psychiatric symptoms often encountered in Parkinson's disease associated with phosphatase and tensin homolog-induced putative kinase 1 mutation. PMID- 20356855 TI - Resting state networks change in clinically isolated syndrome. AB - Task-functional magnetic resonance imaging studies have shown that early cortical recruitment exists in multiple sclerosis, which can partly explain the discrepancy between conventional magnetic resonance imaging and clinical disability. The study of the brain 'at rest' may provide additional information, because task-induced metabolic changes are relatively small compared to the energy use of the resting brain. We therefore questioned whether functional changes exist at rest in the early phase of multiple sclerosis, and addressed this question by a network analysis of no-task functional magnetic resonance imaging data. Fourteen patients with symptoms suggestive of multiple sclerosis (clinically isolated syndrome), 31 patients with relapsing remitting multiple sclerosis and 41 healthy controls were included. Resting state functional magnetic resonance imaging data were brought to standard space using non-linear registration, and further analysed using multi-subject independent component analysis and individual time-course regression. Eight meaningful resting state networks were identified in our subjects and compared between the three groups with non-parametric permutation testing, using threshold-free cluster enhancement to correct for multiple comparisons. Additionally, quantitative measures of structural damage were obtained. Grey and white matter volumes, normalized for head size, were measured for each subject. White matter integrity was investigated with diffusion tensor measures that were compared between groups voxel-wise using tract-based spatial statistics. Patients with clinically isolated syndrome showed increased synchronization in six of the eight resting state networks, including the default mode network and sensorimotor network, compared to controls or relapsing remitting patients. No significant decreases were found in patients with clinically isolated syndrome. No significant resting state synchronization differences were found between relapsing remitting patients and controls. Normalized grey matter volume was decreased and white matter diffusivity measures were abnormal in relapsing remitting patients compared to controls, whereas no atrophy or diffusivity changes were found for the clinically isolated syndrome group. Thus, early synchronization changes are found in patients with clinically isolated syndrome that are suggestive of cortical reorganization of resting state networks. These changes are lost in patients with relapsing remitting multiple sclerosis with increasing brain damage, indicating that cortical reorganization of resting state networks is an early and finite phenomenon in multiple sclerosis. PMID- 20356856 TI - Estimating screening test sensitivity and tumour progression using tumour size and time since previous screening. AB - As mammography screening aims to improve the prognosis through earlier detection/treatment, tumour progression and screening test sensitivity (STS) represent key parameters in the evaluation of screening programs. We will here study some methods for estimation of tumour progression and STS, and show how previously used methods can be combined and developed to utilise more of the data available in modern screening programs. Weedon-Fekjaer et al. recently suggested a study design using interview data about time since previous screening to estimate tumour progression and STS in a stepwise Markov model. While useful, the approach does not utilise tumour size measurements, nor link tumour progression to tumour size. Hence, we will here propose formulas for estimating tumour progression and STS using a continuous tumour growth model. To estimate tumour progression and STS, tumour growth curves are followed from one screening to the next, and probabilities for all combinations of tumour sizes at repeated screening examinations calculated. Based on the probabilities for screening detection on subsequent screening examinations, maximum likelihood estimates are calculated. Applied to Norwegian data, the new approach gives similar results to previously published results based on interval data, confirming the earlier estimated large variation in tumour growth rates. PMID- 20356858 TI - Evaluation of cancer service screening: case referent studies recommended. AB - Various cancer screening trials, randomised or otherwise controlled, have demonstrated reductions in cancer mortality. As a consequence, population screening programmes have been implemented. In the mean time, major advances are being made in early detection and treatment modalities of specific cancers and pre-cancers. The impact of these improvements should have bearing on the beneficial effect of periodical screening in preventing cancer death. To monitor these dynamics in the effectiveness of screening, case-referent studies are designed. The effectiveness is estimated by calculating an odds ratio indicating the cancer death rate in screened versus not screened invitees. The major criticisms of case referent studies are potential selection bias and confounding bias of the odds ratio. By properly designing and applying sensitivity analyses these biases can be minimised. PMID- 20356857 TI - Modelling the cumulative risk of a false-positive screening test. AB - The goal of a screening test is to reduce morbidity and mortality through the early detection of disease; but the benefits of screening must be weighed against potential harms, such as false-positive (FP) results, which may lead to increased healthcare costs, patient anxiety, and other adverse outcomes associated with diagnostic follow-up procedures. Accurate estimation of the cumulative risk of an FP test after multiple screening rounds is important for program evaluation and goal setting, as well as informing individuals undergoing screening what they should expect from testing over time. Estimation of the cumulative FP risk is complicated by the existence of censoring and possible dependence of the censoring time on the event history. Current statistical methods for estimating the cumulative FP risk from censored data follow two distinct approaches, either conditioning on the number of screening tests observed or marginalizing over this random variable. We review these current methods, identify their limitations and possibly unrealistic assumptions, and propose simple extensions to address some of these limitations. We discuss areas where additional extensions may be useful. We illustrate methods for estimating the cumulative FP recall risk of screening mammography and investigate the appropriateness of modelling assumptions using 13 years of data collected by the Breast Cancer Surveillance Consortium (BCSC). In the BCSC data we found evidence of violations of modelling assumptions of both classes of statistical methods. The estimated risk of an FP recall after 10 screening mammograms varied between 58% and 77% depending on the approach used, with an estimate of 63% based on what we feel are the most reasonable modelling assumptions. PMID- 20356860 TI - Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat. AB - Arsenic is an ubiquitous and well-documented carcinogenic metalloid. The most common source of arsenic is drinking water. The mechanism of arsenic toxicity in a cell has historically been centered around its inhibitory effects on cellular respiration and mitochondrial injury. Ascorbic acid, a low molecular weight, water-soluble antioxidant, improves the reduced glutathione (GSH) status by recycling oxidized glutathione. Ascorbic acid can improve mitochondrial function by improving the thiol status; thereby preventing reactive oxygen species- mediated damage to liver as well as kidney. Ascorbic acid has been shown to protect membrane and other cellular compartments by regenerating vitamin E. Therefore, ascorbic acid seems to be a suitable protective factor against arsenic toxicity. Present reports describe the effect of ascorbic acid on oxidative phosphorylation, adenosine triphosphatase (ATPase), succinic dehydrogenase, caspase-3 and apoptosis in the liver of rats treated with arsenic trioxide (As(III)). Ultrastructural changes in the mitochondria have also been reported. We show that cotreatments with ascorbic acid and As(III) improve mitochondrial structure and function. We attribute these improvements mainly to antioxidative role of ascorbic acid. Apoptosis was restricted due to caspase-3 inhibition. Ascorbic acid could protect DNA from the attack of reactive oxygen species generated by As(III). Consequently its events led to improved ADP:O ratio, normalized ATPase activity and restored the activity of succinic dehydrogenase. Overall, results support the protective role of ascorbic acid against As( III) induced liver injury. PMID- 20356859 TI - Polychlorinated biphenyls have inhibitory effect on testicular steroidogenesis by downregulation of P450(17alpha) and P450(scc). AB - Polychlorinated biphenyls (PCBs) are environmental pollutants that are quite toxic to biological systems. This study examined the inhibitory effect of PCB126 and PCB114 on testicular steroidogenesis in male rats. Male Sprague Dawley rats received weekly intraperitoneal injections of PCB126 (0.2 mg/kg) or PCB114 (20 mg/kg) or vehicle (corn oil). Animals from each group were sacrificed at 2, 5 and 8 weeks after the injections. Blood and testis tissue samples were collected for the hormone assay, Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). The testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were assayed, and the expression levels of the mRNA and proteins associated with the testosterone biosynthesis pathway were measured to determine the effect of PCB126 and PCB114 on testicular steroidogenesis. The results showed that the testis weight was significantly higher in the PCB126-treated rats given eight shots. Moreover, the serum testosterone levels were significantly lower in the PCB126 and PCB114-treated groups than the control. The transcription and translation levels of P450(17alpha) and P450(scc) were significantly lower in the PCB126-treated groups than the control. These results suggest that PCB126 may affect testicular steroidogenesis by downregulating P450(17alpha), P450(scc) and have inhibitory effect on the testicular functions. PMID- 20356861 TI - Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells. AB - Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625-1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism. PMID- 20356862 TI - Birth registration is a priority for child survival. PMID- 20356863 TI - Early postoperative detection of tissue necrosis in amputation stumps with indocyanine green fluorescence angiography. AB - OBJECTIVE: Amputations of the lower extremity due to irreversible ischemic tissue loss are performed as distally as possible. Therefore, oftentimes wound-healing disorders develop, requiring additional surgical treatment. METHODS: The amputations stumps of 10 patients with irreversible ischemic tissue loss due to arteriosclerosis were investigated within 72 hours postoperatively with indocyanine green (ICG) fluorescence. RESULTS: For 6 of the investigated stumps, no perfusion deficit could be seen through fluorescence angiography. All stumps displayed primary healing. In the fluorescence angiography of 3 amputations, stump perfusions deficits predicted later tissue necrosis and had to be amputated again in a second operation. One amputation wound showed a small ICG perfusion deficit that represented a blood clot. CONCLUSION: Indocyanine green fluorescence angiography allows a perfusion analysis of amputation stumps and therefore a prediction of the expected tissue necrosis. This tool may allow reliable prediction of amputation level. PMID- 20356864 TI - Markers of proteolysis, fibrinolysis, and coagulation in relation to size and growth rate of abdominal aortic aneurysms. AB - We evaluated whether matrix metalloproteinases (MMPs) 2 and 9, their inhibitors, markers for fibrinolysis, and thrombin activation are associated with diameter and growth of abdominal aortic aneurysms (AAAs). MATERIAL AND METHODS: Matrix metalloproteinases 2 and 9, tissue inhibitor of MMPs (TIMP-1), serpine-1, tPa serpine-1, and activated protein C- protein C inhibitor (APC-PCI) complex were analyzed in 353 patients with AAA grouped according to AAA size, and 219 gender- and age-matched healthy individuals. Follow-up of AAA growth for up to 7 years was possible in 178 of 353 patients. RESULTS: At baseline, all groups of patients with AAA showed lower levels of MMP-2 and -9, and higher levels of TIMP-1, serpine-1, and t-Pa-serpine-1 than controls. Matrix metalloproteinase 2 correlated inversely and APC-PCI complex correlated directly with AAA diameter. We found no correlations between markers for proteolysis, fibrinolysis, coagulation, and yearly AAA growth. CONCLUSION: Matrix metalloproteinase 2 is lower and APC-PCI higher in patients with larger AAA, but the relevance of the markers for AAA growth is far from clarified. PMID- 20356865 TI - Tension hemothorax following endovascular thoracic aortic transection repair: case report. AB - Thoracic aortic transection (TAT) is the second commonest cause of death from blunt trauma surpassed only by head injury and is associated with a mortality of 80% to 90%. The injury site is typically anteromedial at the aortic isthmus where differential shear forces act during rapid deceleration. The authors report a lateral aortic laceration managed by endovascular repair that required open thoracotomy for tension hemothorax resulting from an endoleak. PMID- 20356866 TI - Correlation of cerebral oximetry with internal carotid artery stump pressures in carotid endarterectomy. AB - OBJECTIVE: This study compares internal carotid artery (ICA) mean stump pressures (SPs) with cerebral oximetry monitoring during carotid endarterectomy (CEA). METHODS: A total of 104 consecutive patients undergoing CEA under general anesthesia (GA) during a 10-month period were prospectively evaluated. Baseline and postcarotid clamp regional cerebral oxygen saturation (rSO(2)) and mean ICA SPs were measured. Demographic, surgical, and medical variables were recorded for each case. RESULTS: There were no postoperative strokes. Thirteen patients were excluded because of incomplete data. Of the 40 patients who had <10% drop in rSO(2), 6 had SP <40 mm Hg. Regional cerebral oxygen saturation with a 15% saturation drop threshold was 76.3% sensitive and 81.1% specific in detecting patients with SP <40 mm Hg. With a threshold of 20% drop, sensitivity and specificity were 57.9% and 86.8%, respectively. CONCLUSIONS: Relative drop in rSO( 2) is neither sensitive nor specific in detecting patients with mean SP <40 mm Hg. These data do not support the use of cerebral oximetry as the sole monitoring modality during carotid endarterectomy under GA. PMID- 20356867 TI - Endovascular occlusion of a ruptured popliteal artery aneurysm. AB - Popliteal artery aneurysms are the most common of the peripheral aneurysms. Rupture is a rare complication of these aneurysms. Here we present a case of a ruptured popliteal aneurysm in a patient with severe joint disease and immobility due to rheumatoid arthritis. The condition was treated endovascularly with an Amplatzer arterial occlusion device. The aneurysm was successfully thrombosed without inducing critical limb ischemia, as the distal popliteal was chronically occluded. Ligation of peripheral aneurysms is an infrequent treatment without simultaneous bypass graft placement. Endovascular occlusion of ruptured popliteal aneurysms should be considered a valid therapeutic strategy where exclusion bypass is not required due to distal arterial occlusion. PMID- 20356869 TI - Persistent high alcohol consumption in alcohol-preferring (P) rats results from a lack of normal aversion to alcohol. AB - AIMS: In this study, we tested the impact of pretreatment with alcohol on subsequent alcohol drinking in outbred Sprague-Dawley and selectively bred alcohol-preferring (P) rats. METHODS: As a pretreatment, male Sprague-Dawley and P rats were given a passive oral administration of either alcohol (1.0 g/kg) or tap water. Then, they were given free choice of drinking alcohol (5% v/v) or water in their home cages, which was measured over 4 weeks. RESULTS: Without alcohol pretreatment, there was no significant strain difference in alcohol preference; both strains preferred 5% (v/v) alcohol solution. The strain difference was only apparent in the groups given alcohol pretreatment. This arose from the fact that alcohol pretreatment significantly reduced alcohol preference in the Sprague-Dawley rats to a level well below 50%, while it did not alter drinking behavior in P rats. The same effects were seen with total alcohol consumption (g/kg/day). These effects persisted throughout the 4 weeks of the study. CONCLUSIONS: The principal difference between the Sprague-Dawley and P rats was that the P rats did not show the normal aversion to alcohol after forced exposure to alcohol that the Sprague-Dawley rats showed. One of the potential contributors to high alcohol intake and preference in P rats may be lack of sensitivity to aversive effects of alcohol. PMID- 20356870 TI - Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme. AB - AIMS: Heart failure (HF) and chronic obstructive pulmonary disease are common partners. Bronchodilators are associated with adverse cardiovascular outcomes in patients with pulmonary disease. The outcome of patients with HF prescribed bronchodilators is poorly defined. METHODS AND RESULTS: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomized 7599 patients with symptomatic HF to receive candesartan or placebo. The relative risk conveyed by bronchodilator therapy was examined using a multivariable Cox proportional hazards model. The prevalence of bronchodilator therapy was similar in patients with reduced and preserved systolic function (respectively, 8.7 vs. 9.2%, P = 0.46). Beta-blocker utilization was markedly lower in patients receiving bronchodilators compared with those without (overall 31.9 vs. 57.6%, P < 0.0001). Bronchodilator use was associated with increased all cause mortality [HR 1.26 (1.09-1.45), P = 0.0015], cardiovascular death [HR 1.21 (1.03-1.42), P = 0.0216], HF hospitalization [HR 1.49 (1.29-1.72), P < 0.0001], and major adverse cardiovascular events [HR 1.32 (1.17-1.76), P < 0.0001]. The adverse outcomes were consistent in patients with reduced and preserved systolic function. No significant interaction was observed between bronchodilators and beta-blockade with respect to outcomes. CONCLUSION: Bronchodilator use is a powerful independent predictor of worsening HF and increased mortality in a broad spectrum of patients with HF. Whether this relates to a toxic effect of bronchodilators, underlying pulmonary disease, or both is unclear and warrants further investigation. PMID- 20356868 TI - Hyperglycaemia-induced cardiomyocyte death is mediated via MCP-1 production and induction of a novel zinc-finger protein MCPIP. AB - AIMS: Cardiomyocyte apoptosis contributes to the development of diabetic cardiomyopathy. How the elevated glucose levels associated with diabetes cause cell death is unknown. Here we report that high glucose-induced cardiomyocyte death is mediated via monocyte chemotactic protein-1 (MCP-1) production and induction of a novel zinc-finger protein. METHODS AND RESULTS: H9c2 cardiomyoblasts treated with 28 mmol/L glucose were evaluated for MCP-1 production and induction of the zinc-finger protein, MCP-1-induced protein (MCPIP). Disruptors of MCP-1 interaction with its receptor, CCR2, and knockdown of MCPIP with siRNA were used to determine if MCP-1 and MCPIP mediate glucose induced cell death. The molecular mechanisms were evaluated by assessing reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and autophagy. Key findings were confirmed in isolated neonatal rat cardiomyocytes. Glucose treatment of H9c2 cardiomyoblasts and isolated cardiomyocytes caused MCP 1 production, MCPIP induction, ROS production, ER stress, autophagy, and cell death. Treatment with CCR2 antagonists and knockdown of MCPIP attenuated glucose induced ROS production, ER stress, autophagy, and cell death. Inhibition of ROS with 1400 W, tiron, and cerium oxide (CeO(2)) nanoparticles attenuated ER stress, autophagy, and cell death. Specific inhibitors of ER stress and knockdown of IRE 1 attenuated glucose-induced autophagy and cell death. Inhibitors of autophagy and knockdown of beclin-1 attenuated glucose-induced death. CONCLUSION: Glucose induced cardiomyocyte death is mediated via MCP-1 production and MCPIP induction, which causes sequential events--ROS production, ER stress, autophagy, and cell death. PMID- 20356871 TI - Cardiac manifestations of mitochondrial disorders. PMID- 20356872 TI - Mechanosensitivity of ion channels based on protein-lipid interactions. AB - Ion channels form a group of membrane proteins that pass ions through a pore beyond the energy barrier of the lipid bilayer. The structure of the transmembrane segment of membrane proteins is influenced by the charges and the hydrophobicity of the surrounding lipids and the pressure on its surface. A mechanosensitive channel is specifically designed to change its conformation in response to changes in the membrane pressure (tension). However, mechanosensitive channels are not the only group that is sensitive to the physical environment of the membrane: voltage-gated channels are also amenable to the lipid environment. In this article, we review the structure and gating mechanisms of the mechanosensitive channels and voltage-gated channels and discuss how their functions are affected by the physical properties of the lipid bilayer. PMID- 20356873 TI - Computational model of cell positioning: directed and collective migration in the intestinal crypt epithelium. AB - The epithelium of the intestinal crypt is a dynamic tissue undergoing constant regeneration through cell growth, cell division, cell differentiation and apoptosis. How the epithelial cells maintain correct positioning and how they migrate in a directed and collective fashion are still not well understood. In this paper, we developed a computational model to elucidate these processes. We show that differential adhesion between epithelial cells, caused by the differential activation of EphB receptors and ephrinB ligands along the crypt axis, is necessary to regulate cell positioning. Differential cell adhesion has been proposed previously to guide cell movement and cause cell sorting in biological tissues. The proliferative cells and the differentiated post-mitotic cells do not intermingle as long as differential adhesion is maintained. We also show that, without differential adhesion, Paneth cells are randomly distributed throughout the intestinal crypt. In addition, our model suggests that, with differential adhesion, cells migrate more rapidly as they approach the top of the intestinal crypt. Finally, by calculating the spatial correlation function of the cell velocities, we observe that differential adhesion results in the differentiated epithelial cells moving in a coordinated manner, where correlated velocities are maintained at large distances, suggesting that differential adhesion regulates coordinated migration of cells in tissues. PMID- 20356874 TI - Live cell imaging of mechanotransduction. AB - Mechanical forces play important roles in the regulation of cellular functions, including polarization, migration and stem cell differentiation. Tremendous advancement in our understanding of mechanotransduction has been achieved with the recent development of imaging technologies and molecular biosensors. In particular, genetically encoded biosensors based on fluorescence resonance energy transfer (FRET) technology have been widely developed and applied in the field of mechanobiology. In this article, we will provide an overview of the recent progress of FRET application in mechanobiology, specifically mechanotransduction. We first introduce fluorescent proteins and FRET technology. We then discuss the mechanotransduction processes in different cells including stem cells, with a special emphasis on the important signalling molecules involved in mechanotransduction. Finally, we discuss methods that can allow the integration of simultaneous FRET imaging and mechanical stimulation to trigger signalling transduction. In summary, FRET technology has provided a powerful tool for the study of mechanotransduction to advance our systematic understanding of the molecular mechanisms by which cells respond to mechanical stimulation. PMID- 20356875 TI - Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells. AB - The past decade has seen significant increases in combustion-generated ambient particles, which contain a nanosized fraction (less than 100 nm), and even greater increases have occurred in engineered nanoparticles (NPs) propelled by the booming nanotechnology industry. Although inhalation of these particulates has become a public health concern, human health effects and mechanisms of action for NPs are not well understood. Focusing on the human airway smooth muscle cell, here we show that the cellular mechanical function is altered by particulate exposure in a manner that is dependent upon particle material, size and dose. We used Alamar Blue assay to measure cell viability and optical magnetic twisting cytometry to measure cell stiffness and agonist-induced contractility. The eight particle species fell into four categories, based on their respective effect on cell viability and on mechanical function. Cell viability was impaired and cell contractility was decreased by (i) zinc oxide (40-100 nm and less than 44 microm) and copper(II) oxide (less than 50 nm); cell contractility was decreased by (ii) fluorescent polystyrene spheres (40 nm), increased by (iii) welding fumes and unchanged by (iv) diesel exhaust particles, titanium dioxide (25 nm) and copper(II) oxide (less than 5 microm), although in none of these cases was cell viability impaired. Treatment with hydrogen peroxide up to 500 microM did not alter viability or cell mechanics, suggesting that the particle effects are unlikely to be mediated by particle-generated reactive oxygen species. Our results highlight the susceptibility of cellular mechanical function to particulate exposures and suggest that direct exposure of the airway smooth muscle cells to particulates may initiate or aggravate respiratory diseases. PMID- 20356876 TI - Emergence of a prestressed eukaryotic nucleus during cellular differentiation and development. AB - Nuclear shape and size are emerging as mechanistic regulators of genome function. Yet, the coupling between chromatin assembly and various nuclear and cytoplasmic scaffolds is poorly understood. The present work explores the structural organization of a prestressed nucleus in a variety of cellular systems ranging from cells in culture to those in an organism. A combination of laser ablation and cellular perturbations was used to decipher the dynamic nature of the nucleo cytoplasmic contacts. In primary mouse embryonic fibroblasts, ablation of heterochromatin nodes caused an anisotropic shrinkage of the nucleus. Depolymerization of actin and microtubules, and inhibition of myosin motors, resulted in the differential stresses that these cytoplasmic systems exert on the nucleus. The onset of nuclear prestress was then mapped in two contexts--first, in the differentiation of embryonic stem cells, where signatures of prestress appeared with differentiation; second, at an organism level, where nuclear or cytoplasmic laser ablations of cells in the early Drosophila embryo induced a collapse of the nucleus only after cellularization. We thus show that the interplay of physical connections bridging the nucleus with the cytoplasm governs the size and shape of a prestressed eukaryotic nucleus. PMID- 20356877 TI - Stance and swing phase costs in human walking. AB - Leg swing in human walking has historically been viewed as a passive motion with little metabolic cost. Recent estimates of leg swing costs are equivocal, covering a range from 10 to 33 per cent of the net cost of walking. There has also been a debate as to whether the periods of double-limb support during the stance phase dominate the cost of walking. Part of this uncertainty is because of our inability to measure metabolic energy consumption in individual muscles during locomotion. Therefore, the purpose of this study was to investigate the metabolic cost of walking using a modelling approach that allowed instantaneous energy consumption rates in individual muscles to be estimated over the full gait cycle. At a typical walking speed and stride rate, leg swing represented 29 per cent of the total muscular cost. During the stance phase, the double-limb and single-limb support periods accounted for 27 and 44 per cent of the total cost, respectively. Performing step-to-step transitions, which encompasses more than just the double-support periods, represented 37 per cent of the total cost of walking. Increasing stride rate at a constant speed led to greater double-limb support costs, lower swing phase costs and no change in single-limb support costs. Together, these results provide unique insight as to how metabolic energy is expended over the human gait cycle. PMID- 20356878 TI - Intercellular mechanotransduction during multicellular morphodynamics. AB - Multicellular structures are held together by cell adhesions. Forces that act upon these adhesions play an integral role in dynamically re-shaping multicellular structures during development and disease. Here, we describe different modes by which mechanical forces are transduced in a multicellular context: (i) indirect mechanosensing through compliant substratum, (ii) cytoskeletal 'tug-of-war' between cell-matrix and cell-cell adhesions, (iii) cortical contractility contributing to line tension, (iv) stresses associated with cell proliferation, and (v) forces mediating collective migration. These modes of mechanotransduction are recurring motifs as they play a key role in shaping multicellular structures in a wide range of biological contexts. Tissue morphodynamics may ultimately be understood as different spatio-temporal combinations of a select few multicellular transformations, which in turn are driven by these mechanotransduction motifs that operate at the bicellular to multicellular length scale. PMID- 20356879 TI - Insights into the mechanisms of myosin and kinesin molecular motors from the single-molecule unbinding force measurements. AB - In cells, ATP (adenosine triphosphate)-driven motor proteins, both cytoskeletal and nucleic acid-based, operate on their corresponding 'tracks', that is, actin, microtubules or nucleic acids, by converting the chemical energy of ATP hydrolysis into mechanical work. During each mechanochemical cycle, a motor proceeds via several nucleotide states, characterized by different affinities for the 'track' filament and different nucleotide (ATP or ADP) binding kinetics, which is crucial for a motor to efficiently perform its cellular functions. The measurements of the rupture force between the motor and the track by applying external loads to the individual motor-substrate bonds in various nucleotide states have proved to be an important tool to obtain valuable insights into the mechanism of the motors' performance. We review the application of this technique to various linear molecular motors, both processive and non-processive, giving special attention to the importance of the experimental geometry. PMID- 20356880 TI - Laminar flow around corners triggers the formation of biofilm streamers. AB - Bacterial biofilms have an enormous impact on medicine, industry and ecology. These microbial communities are generally considered to adhere to surfaces or interfaces. Nevertheless, suspended filamentous biofilms, or streamers, are frequently observed in natural ecosystems where they play crucial roles by enhancing transport of nutrients and retention of suspended particles. Recent studies in streamside flumes and laboratory flow cells have hypothesized a link with a turbulent flow environment. However, the coupling between the hydrodynamics and complex biofilm structures remains poorly understood. Here, we report the formation of biofilm streamers suspended in the middle plane of curved microchannels under conditions of laminar flow. Experiments with different mutant strains allow us to identify a link between the accumulation of extracellular matrix and the development of these structures. Numerical simulations of the flow in curved channels highlight the presence of a secondary vortical motion in the proximity of the corners, which suggests an underlying hydrodynamic mechanism responsible for the formation of the streamers. Our findings should be relevant to the design of all liquid-carrying systems where biofilms are potentially present and provide new insights on the origins of microbial streamers in natural and industrial environments. PMID- 20356881 TI - A theoretical study of diffusional transport over the alveolar surfactant layer. AB - In this communication, we analyse the passage of oxygen and carbon dioxide over the respiratory membrane. The lung surfactant membrane at the alveolar interface can have a very special arrangement, which affects the diffusional transport. We present a theoretical model for the diffusion of small molecules in membranes with a complex structure, and we specifically compare a membrane composed of a tubular bilayer network with a membrane consisting of a stack of bilayers. Oxygen and carbon dioxide differ in terms of their solubility in the aqueous and the lipid regions of the membrane, and we show that this difference clearly influences their transport properties in the different membrane structures. During normal respiration, the rate-limiting step for carbon dioxide transport is in the gas phase of the different compartments in the lung. For oxygen, on the other hand, the rate is limited by the transport between alveoli and the capillary blood vessels, including the lung surfactant membrane. In a membrane with a structure of a continuous tubular lipid network, oxygen transport is facilitated to a significant extent compared with the structure of aligned lipid bilayers. The model calculations in the present study show that transport of oxygen through the tubular structure is indeed ca 30 per cent faster than transport through a membrane composed of stacked bilayers. The tubular network will also facilitate the transport of apolar substances between the gas phase and the blood. Important examples are ethanol and other volatile liquids that can leave the blood through the lungs, and gaseous anaesthetics or volatile solvents that are inhaled. This exemplifies a new physiological role of a tubular lipid network in the lung surfactant membrane. PMID- 20356882 TI - Scaling relationship between tree respiration rates and biomass. AB - The WBE theory proposed by West, Brown and Enquist predicts that larger plant respiration rate, R, scales to the three-quarters power of body size, M. However, studies on the R versus M relationship for larger plants (i.e. trees larger than saplings) have not been reported. Published respiration rates of field-grown trees (saplings and larger trees) were examined to test this relationship. Our results showed that for larger trees, aboveground respiration rates RA scaled as the 0.82-power of aboveground biomass MA, and that total respiration rates RT scaled as the 0.85-power of total biomass MT, both of which significantly deviated from the three-quarters scaling law predicted by the WBE theory, and which agreed with 0.81-0.84-power scaling of biomass to respiration across the full range of measured tree sizes for an independent dataset reported by Reich et al. (Reich et al. 2006 Nature 439, 457-461). By contrast, R scaled nearly isometrically with M in saplings. We contend that the scaling exponent of plant metabolism is close to unity for saplings and decreases (but is significantly larger than three-quarters) as trees grow, implying that there is no universal metabolic scaling in plants. PMID- 20356883 TI - Proximate determinants of telomere length in sand lizards (Lacerta agilis). AB - Telomeres are repeat sequences of non-coding DNA that cap the ends of chromosomes and contribute to their stability and the genomic integrity of cells. In evolutionary ecology, the main research target regarding these genomic structures has been their role in ageing and as a potential index of age. However, research on humans shows that a number of traits contribute to among-individual differences in telomere length, in particular traits enhancing cell division and genetic erosion, such as levels of free radicals and stress. In lizards, tail loss owing to predation attempts results in a stress-induced shift to a more cryptic lifestyle. In sand lizard (Lacerta agilis) males, telomere length was compromised by tail regrowth in a body size-related manner, so that small males, which already exhibit more cryptic mating tactics, were less affected than larger males. Tail regrowth just fell short of having a significant relationship with telomere length in females, and so did age in males. In females, there was a significant positive relationship between age and telomere length. We conclude that the proximate effect of compromised antipredation and its associated stress seems to have a more pronounced effect in males than in females and that age associated telomere dynamics differ between the sexes. PMID- 20356884 TI - Breaking the trade-off: rainforest bats maximize bandwidth and repetition rate of echolocation calls as they approach prey. AB - Both mammals and birds experience a performance trade-off between producing vocalizations with high bandwidths and at high repetition rate. Echolocating bats drastically increase repetition rate from 2-20 calls s(-1) up to about 170 calls s(-1) prior to intercepting airborne prey in order to accurately track prey movement. In turn, bandwidth drops to about 10-30 kHz for the calls of this 'final buzz'. We have now discovered that Southeast Asian rainforest bats (in the vespertilionid subfamilies Kerivoulinae and Murininae) are able to maintain high call bandwidths at very high repetition rates throughout approach to prey. Five species of Kerivoula and Phoniscus produced call bandwidths of between 78 and 170 kHz at repetition rates of 140-200 calls s(-1) and two of Murina at 80 calls s( 1). The 'typical' and distinct drop in call frequency was present in none of the seven species. This stands in striking contrast to our present view of echolocation during approach to prey in insectivorous bats, which was established largely based on European and American members of the same bat family, the Vespertilionidae. Buzz calls of Kerivoula pellucida had mean bandwidths of 170 kHz and attained maximum starting frequencies of 250 kHz which makes them the most broadband and most highly pitched tonal animal vocalization known to date. We suggest that the extreme vocal performance of the Kerivoulinae and Murininae evolved as an adaptation to echolocating and tracking arthropods in the dense rainforest understorey. PMID- 20356886 TI - Social learning in a non-social reptile (Geochelone carbonaria). AB - The ability to learn from the actions of another is adaptive, as it is a shortcut for acquiring new information. However, the evolutionary origins of this trait are still unclear. There is evidence that group-living mammals, birds, fishes and insects can learn through observation, but this has never been investigated in reptiles. Here, we show that the non-social red-footed tortoise (Geochelone carbonaria) can learn from the actions of a conspecific in a detour task; non observer animals (without a conspecific demonstrator) failed. This result provides the first evidence that a non-social species can use social cues to solve a task that it cannot solve through individual learning, challenging the idea that social learning is an adaptation for social living. PMID- 20356885 TI - Blindsnake evolutionary tree reveals long history on Gondwana. AB - Worm-like snakes (scolecophidians) are small, burrowing species with reduced vision. Although largely neglected in vertebrate research, knowledge of their biogeographical history is crucial for evaluating hypotheses of snake origins. We constructed a molecular dataset for scolecophidians with detailed sampling within the largest family, Typhlopidae (blindsnakes). Our results demonstrate that scolecophidians have had a long Gondwanan history, and that their initial diversification followed a vicariant event: the separation of East and West Gondwana approximately 150 Ma. We find that the earliest blindsnake lineages, representing two new families described here, were distributed on the palaeolandmass of India+Madagascar named here as Indigascar. Their later evolution out of Indigascar involved vicariance and several oceanic dispersal events, including a westward transatlantic one, unexpected for burrowing animals. The exceptional diversification of scolecophidians in the Cenozoic was probably linked to a parallel radiation of prey (ants and termites) as well as increased isolation of populations facilitated by their fossorial habits. PMID- 20356887 TI - Nutrient provisioning facilitates homeostasis between tsetse fly (Diptera: Glossinidae) symbionts. AB - Host-associated microbial interactions may involve genome complementation, driving-enhanced communal efficiency and stability. The tsetse fly (Diptera: Glossinidae), the obligate vector of African trypanosomes (Trypanosoma brucei subspp.), harbours two enteric Gammaproteobacteria symbionts: Wigglesworthia glossinidia and Sodalis glossinidius. Host coevolution has streamlined the Wigglesworthia genome to complement the exclusively sanguivorous tsetse lifestyle. Comparative genomics reveal that the Sodalis genome contains the majority of Wigglesworthia genes. This significant genomic overlap calls into question why tsetse maintains the coresidence of both symbionts and, furthermore, how symbiont homeostasis is maintained. One of the few distinctions between the Wigglesworthia and Sodalis genomes lies in thiamine biosynthesis. While Wigglesworthia can synthesize thiamine, Sodalis lacks this capability but retains a thiamine ABC transporter (tbpAthiPQ) believed to salvage thiamine. This genetic complementation may represent the early convergence of metabolic pathways that may act to retain Wigglesworthia and evade species antagonism. We show that thiamine monophosphate, the specific thiamine derivative putatively synthesized by Wigglesworthia, impacts Sodalis thiamine transporter expression, proliferation and intracellular localization. A greater understanding of tsetse symbiont interactions may generate alternative control strategies for this significant medical and agricultural pest, while also providing insight into the evolution of microbial associations within hosts. PMID- 20356888 TI - Chaotic Red Queen coevolution in three-species food chains. AB - Coevolution between two antagonistic species follows the so-called 'Red Queen dynamics' when reciprocal selection results in an endless series of adaptation by one species and counteradaptation by the other. Red Queen dynamics are 'genetically driven' when selective sweeps involving new beneficial mutations result in perpetual oscillations of the coevolving traits on the slow evolutionary time scale. Mathematical models have shown that a prey and a predator can coevolve along a genetically driven Red Queen cycle. We found that embedding the prey-predator interaction into a three-species food chain that includes a coevolving superpredator often turns the genetically driven Red Queen cycle into chaos. A key condition is that the prey evolves fast enough. Red Queen chaos implies that the direction and strength of selection are intrinsically unpredictable beyond a short evolutionary time, with greatest evolutionary unpredictability in the superpredator. We hypothesize that genetically driven Red Queen chaos could explain why many natural populations are poised at the edge of ecological chaos. Over space, genetically driven chaos is expected to cause the evolutionary divergence of local populations, even under homogenizing environmental fluctuations, and thus to promote genetic diversity among ecological communities over long evolutionary time. PMID- 20356889 TI - Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links. AB - Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1 43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1-4 days later (P1-P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0-20 h. We found that the structure and function were abolished by BAPTA. In P0-P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3-P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients. PMID- 20356890 TI - DNA transposon dynamics in populations of Daphnia pulex with and without sex. AB - We investigate the role of recombination in transposable element (TE) proliferation in the cyclical parthenogen, Daphnia pulex. Recombination provides a mechanism by which the rate of both TE gain and loss can be accelerated, a duality that has long intrigued many biologists interested in the influence of sex on mutation accumulation. We compared TE loads among populations of D. pulex where sex occurs regularly (cyclical parthenogens or 'sexuals') with those in which the ability to reproduce sexually has been completely lost (obligate 'asexuals') for six different families of DNA transposons. Transposon display assays showed that sexuals have more TEs than asexuals, contrary to the expectations under Muller's ratchet but consistent with the idea that sex facilitates TE spread. Sexuals also exhibit higher insertion site polymorphism among lineages, as predicted because recombination accelerates rates of loss and gain. Asexuals, however, have proportionally more singletons (loci occupied in a single isolate), which differs from previous studies where selfing and outcrossing were used as a proxy for high and low recombination. Our multi element survey reveals that the impact of sex on TE proliferation is consistent among different Class II TE families and we discuss the genomic consequences of different reproductive strategies over long time periods. PMID- 20356891 TI - Temporal genetic change in the last remaining population of woolly mammoth. AB - During the Late Pleistocene, the woolly mammoth (Mammuthus primigenius) experienced a series of local extinctions generally attributed to human predation or environmental change. Some small and isolated populations did however survive far into the Holocene. Here, we investigated the genetic consequences of the isolation of the last remaining mammoth population on Wrangel Island. We analysed 741 bp of the mitochondrial DNA and found a loss of genetic variation in relation to the isolation event, probably caused by a demographic bottleneck or a founder event. However, in spite of ca 5000 years of isolation, we did not detect any further loss of genetic variation. Together with the relatively high number of mitochondrial haplotypes on Wrangel Island near the final disappearance, this suggests a sudden extinction of a rather stable population. PMID- 20356892 TI - Plant green-island phenotype induced by leaf-miners is mediated by bacterial symbionts. AB - The life cycles of many organisms are constrained by the seasonality of resources. This is particularly true for leaf-mining herbivorous insects that use deciduous leaves to fuel growth and reproduction even beyond leaf fall. Our results suggest that an intimate association with bacterial endosymbionts might be their way of coping with nutritional constraints to ensure successful development in an otherwise senescent environment. We show that the phytophagous leaf-mining moth Phyllonorycter blancardella (Lepidoptera) relies on bacterial endosymbionts, most likely Wolbachia, to manipulate the physiology of its host plant resulting in the 'green-island' phenotype--photosynthetically active green patches in otherwise senescent leaves--and to increase its fitness. Curing leaf miners of their symbiotic partner resulted in the absence of green-island formation on leaves, increased compensatory larval feeding and higher insect mortality. Our results suggest that bacteria impact green-island induction through manipulation of cytokinin levels. This is the first time, to our knowledge, that insect bacterial endosymbionts have been associated with plant physiology. PMID- 20356893 TI - A rift between implicit and explicit conditioned valence in human pain relief learning. AB - Pain is aversive, but does the cessation of pain ('relief') have a reward-like effect? Indeed, fruitflies avoid an odour previously presented before a painful event, but approach an odour previously presented after a painful event. Thus, event-timing may turn punishment to reward. However, is event-timing also crucial in humans who can have explicit cognitions about associations? Here, we show that stimuli associated with pain-relief acquire positive implicit valence but are explicitly rated as aversive. Specifically, the startle response, an evolutionarily conserved defence reflex, is attenuated by stimuli that had previously followed a painful event, indicating implicit positive valence of the conditioned stimulus; nevertheless, participants explicitly evaluate these stimuli as 'emotionally negative'. These results demonstrate a rift between the implicit and explicit conditioned valence induced by pain relief. They might explain why humans in some cases are attracted by conditioned stimuli despite explicitly judging them as negative. PMID- 20356894 TI - The function of the aerenchyma in arborescent lycopsids: evidence of an unfamiliar metabolic strategy. AB - Most species of the modern family Isoetaceae (Quillworts) some other modern hydrophytes, use a metabolic pathway for carbon fixation that involves uptake of sedimentary carbon and enrichment of CO(2) in internal gas spaces as a carbon concentrating mechanism. This metabolism, which is related to 'aquatic CAM', is characterized by morphological, physiological and biochemical adaptations for decreasing photorespirative loss, aerating roots and maintaining high growth rates in anoxic, oligotrophic, stressed environments. Some of the closest relatives of the Isoetaceae were the 'arborescent lycopsids', which were among the dominant taxa in the coal swamps found in lowland ecosystems during the Carboniferous and Permian periods (approx. 300 Ma). Morphological, ecological and geochemical evidence supports the hypothesis that the arborescent lycopsids had an unusual metabolism similar to that of modern Isoetaceae and processed a biogeochemically significant proportion of organically fixed carbon over a period of about 100 million years in the late Palaeozoic. The temporal coincidence between the dominance of plants with this metabolism and an anomalous global atmosphere (high O(2); low CO(2)) supports the idea that biosphere feedbacks are important in regulating global climatic homeostasis. The potential influence of this metabolism on the global carbon cycle and its specific adaptive function suggest that it should perhaps be considered a fourth major photosynthetic pathway. PMID- 20356895 TI - Under a neighbour's influence: public information affects stress hormones and behaviour of a songbird. AB - Socially acquired information improves the accuracy and efficiency of environmental assessments and can increase fitness. Public information may be especially useful during unpredictable food conditions, or for species that depend on resources made less predictable by human disturbance. However, the physiological mechanisms by which direct foraging assessments and public information are integrated to affect behaviour remain largely unknown. We tested for potential effects of public information on the behavioural and hormonal response to food reduction by manipulating the social environment of captive red crossbills (Loxia curvirostra). Red crossbills are irruptive migrants that are considered sensitive to changes in food availability and use public information in decision making. Here, we show that public information can attenuate or intensify the release of glucocorticoids (i.e. stress hormones) during food shortage in red crossbills. The observed modulation of corticosterone may therefore be a physiological mechanism linking public information, direct environmental assessments and behavioural change. This mechanism would not only allow for public information to affect individual behaviour, but might also facilitate group decision making by bringing group members into more similar physiological states. The results further suggest that stressors affecting entire populations may be magnified in individual physiology through social interactions. PMID- 20356896 TI - Nanostructure and mechanics of mummified type I collagen from the 5300-year-old Tyrolean Iceman. AB - Skin protects the body from pathogens and degradation. Mummified skin in particular is extremely resistant to decomposition. External influences or the action of micro-organisms, however, can degrade the connective tissue and lay the subjacent tissue open. To determine the degree of tissue preservation in mummified human skin and, in particular, the reason for its durability, we investigated the structural integrity of its main protein, type I collagen. We extracted samples from the Neolithic glacier mummy known as 'the Iceman'. Atomic force microscopy (AFM) revealed collagen fibrils that had characteristic banding patterns of 69 +/- 5 nm periodicity. Both the microstructure and the ultrastructure of dermal collagen bundles and fibrils were largely unaltered and extremely well preserved by the natural conservation process. Raman spectra of the ancient collagen indicated that there were no significant modifications in the molecular structure. However, AFM nanoindentation measurements showed slight changes in the mechanical behaviour of the fibrils. Young's modulus of single mummified fibrils was 4.1 +/- 1.1 GPa, whereas the elasticity of recent collagen averages 3.2 +/- 1.0 GPa. The excellent preservation of the collagen indicates that dehydration owing to freeze-drying of the collagen is the main process in mummification and that the influence of the degradation processes can be addressed, even after 5300 years. PMID- 20356897 TI - In search of the chemical basis for MHC odourtypes. AB - Mice can discriminate between chemosignals of individuals based solely on genetic differences confined to the major histocompatibility complex (MHC). Two different sets of compounds have been suggested: volatile compounds and non-volatile peptides. Here, we focus on volatiles and review a number of publications that have identified MHC-regulated compounds in inbred laboratory mice. Surprisingly, there is little agreement among different studies as to the identity of these compounds. One recent approach to specifying MHC-regulated compounds is to study volatile urinary profiles in mouse strains with varying MHC types, genetic backgrounds and different diets. An unexpected finding from these studies is that the concentrations of numerous compounds are influenced by interactions among these variables. As a result, only a few compounds can be identified that are consistently regulated by MHC variation alone. Nevertheless, since trained animals are readily able to discriminate the MHC differences, it is apparent that chemical studies are somehow missing important information underlying mouse recognition of MHC odourtypes. To make progress in this area, we propose a focus on the search for behaviourally relevant odourants rather than a random search for volatiles that are regulated by MHC variation. Furthermore, there is a need to consider a 'combinatorial odour recognition' code whereby patterns of volatile metabolites (the basis for odours) specify MHC odourtypes. PMID- 20356898 TI - Better perinatal outcomes following transfer of fresh blastocysts and blastocysts cultured from thawed cleavage embryos: a population-based study. AB - BACKGROUND: Fresh embryo transfer results in higher live birth rates, while thawed embryo transfer appears to result in healthier babies. This study aims to investigate the association between the transfer of fresh or thawed embryos at the cleavage or blastocyst stage and the perinatal outcomes. METHODS: This analysis is a retrospective population-based study of 150 376 autologous embryo transfer cycles in Australia during 2002-2006. The rates of pregnancy, live delivery and 'healthy baby' delivery (a single baby born live at term, weighing >or=2500 g, surviving for at least 28 days post birth and not having congenital anomalies) were compared after transfer of fresh cleavage embryos, fresh blastocysts, thawed cleavage embryos, blastocysts from thawed cleavage embryos and thawed blastocysts. RESULTS: The live delivery rate was significantly higher for transfer of fresh blastocysts (27.9%) than for blastocysts cultured from thawed cleavage embryos (22.0%), fresh cleavage embryos (21.7%), thawed blastocysts (16.3%) and thawed cleavage embryos (15.2%). Compared with the transfer of fresh blastocysts, the likelihood of a 'healthy baby' was significantly lower for blastocysts from thawed cleavage embryos [adjusted odds ratios (AOR) 0.73, 95% confidence intervals (CI) 0.65-0.82], fresh cleavage embryos (AOR 0.67, 95% CI 0.64-0.69), thawed blastocysts (AOR 0.57, 95% CI 0.53 0.62) and thawed cleavage embryos (AOR 0.53, 95% CI 0.51-0.56). Of thaw cycles, transfers of thawed blastocysts (AOR 0.79, 95% CI 0.70-0.89) and thawed cleavage embryos (AOR 0.71, 95% CI 0.63-0.79) had significantly lower odds of 'healthy baby' than transfer of blastocysts from thawed cleavage embryos. CONCLUSIONS: These data suggest that an optimum practice model to maximize the outcomes of the birth of a 'healthy baby' is the transfer of blastocysts and the freezing of cleavage embryos in fresh cycles and subsequent transfer of blastocysts cultured from these thawed cleavage embryos. PMID- 20356899 TI - ESX1 gene expression as a robust marker of residual spermatogenesis in azoospermic men. AB - BACKGROUND: It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post meiotic germ cells of the testis in mice. METHODS: We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS: The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS: ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies. PMID- 20356900 TI - Psychological well-being and sexarche in women with polycystic ovary syndrome. AB - BACKGROUND: The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well being as well as sexarche. METHODS: Patients (n = 1148) underwent standardized clinical evaluation. Psychological well-being was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed. RESULTS: Amenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively). CONCLUSIONS: Our results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics. PMID- 20356901 TI - A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-gamma-induced MHC class II molecule on primary human blood macrophages. AB - IL-10, a potent anti-inflammatory cytokine, activates its primary mediator STAT3 to exert inhibitory effects on activated immune response. It has been reported that IFN-gamma signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell-mediated antigen presentation. Cathepsin S, a cysteine protease, plays a significant role in the antigen processing. We hypothesize that the IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-gamma-induced immune responses in primary human blood macrophages. Here, we investigated whether IL-10 perturbs MHC-II levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of cathepsin S and MHC-II, inducible by IFN-gamma, was down-regulated in the presence of IL-10. Additionally, we revealed that the inhibitory effect of IL-10 was demonstrated to be independent of the classical IFN-gamma-induced JAK2/STAT1 signaling cascade or the NF-kappaB pathway. Following STAT3 suppression with specific siRNA, the expression of IFN-gamma-induced surface MHC II antigens and cathepsin S levels was restored, even in the presence of IL-10. Taken together, our results demonstrated that the immunosuppressive effects of IL 10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expression. PMID- 20356902 TI - Memorial: Gary Michael Bokoch, 1954-2010. PMID- 20356903 TI - Editorial: When charge is in charge--"Millikan" for leukocyte biologists. PMID- 20356904 TI - Editorial: Monocyte subpopulations and lentiviral infection. PMID- 20356905 TI - Plasmid double locus sequence typing for IncHI2 plasmids, a subtyping scheme for the characterization of IncHI2 plasmids carrying extended-spectrum beta-lactamase and quinolone resistance genes. AB - OBJECTIVES: IncHI2 plasmids are frequently encountered in clinical enterobacterial strains associated with the dissemination of relevant antimicrobial resistance genes. These plasmids are usually >250 kb, and technical difficulties can impair plasmid DNA purification and comparison by restriction fragment length polymorphism. We analysed the available IncHI2 whole DNA plasmid sequences to devise a rapid typing scheme to categorize the members of this plasmid family into homogeneous groups. METHODS: We compared the available full IncHI2 plasmid sequences, identifying conserved and variable regions within the backbone of this plasmid family, to devise an IncHI2 typing method based on sequence typing and multiplex PCRs. A collection of IncHI2 plasmids carrying extended-spectrum beta-lactamase and quinolone resistance genes, identified in strains from different sources (animals and humans) and geographical origins, was tested by these typing systems. RESULTS: We devised a plasmid double locus sequence typing (pDLST) scheme and a multiplex PCR discriminating IncHI2 plasmid variants. These systems were tested on a collection of IncHI2 plasmids, demonstrating that the plasmids carrying blaCTX-M-2 and blaCTX-M-9 belonged to two major plasmid variants, which were highly conserved among different enterobacterial species disseminated in several European countries. CONCLUSIONS: The ability to recognize and subcategorize plasmids by pDLST in homogeneous groups on the basis of their phylogenetic relatedness can be helpful to analyse their distribution in nature and to discover of their evolutionary origin. PMID- 20356906 TI - rpoB gene mutation profile in rifampicin-resistant Mycobacterium tuberculosis clinical isolates from Guizhou, one of the highest incidence rate regions in China. PMID- 20356907 TI - "Extraordinary Measures": Arrowsmith for the NASDAQ era. PMID- 20356908 TI - Poly(U) cracked the code: a Marshall Nirenberg memoir. PMID- 20356909 TI - Light to sight: milestones in phototransduction. PMID- 20356910 TI - Regarding "Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases". PMID- 20356911 TI - Intravenous infusion of n-3 polyunsaturated fatty acids and inducibility of ventricular tachycardia in patients with implantable cardioverter defibrillator. AB - AIMS: Marine n-3 polyunsaturated fatty acids (PUFA) may have antiarrhythmic effects. The aim of this study was to investigate the effect of intravenously administered n-3 PUFA on the inducibility of ventricular tachycardia (VT) in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: In a randomized, placebo-controlled cross-over study, patients with an ICD underwent two electrophysiological studies using the stimulation possibilities in the ICD preceded by intravenous infusion of either a lipid emulsion delivering 3.9 g n-3 PUFA or placebo (0.9% saline). The level of stimulation required to induce sustained monomorphic VT was ranked in order from least to most aggressive, and non-inducibility was ranked highest. The content of n-3 PUFA in plasma free fatty acids (FFA), plasma phospholipids, and platelet phospholipids was measured by gas chromatography. Eight patients were included, and six of these completed the study. The content of n-3 PUFA as FFA and in platelet phospholipids increased more after n-3 PUFA infusion than after placebo (P<0.001). Of the five patients who were inducible after placebo, two were no longer inducible after n-3 PUFA infusion and another two required stronger stimulation to induce VT. The difference in the stimulation required after placebo and after n-3 PUFA was borderline significant (P=0.063, Wilcoxon signed rank test). CONCLUSION: Intravenous n-3 PUFA tended to decrease VT inducibility, but a larger study is warranted. PMID- 20356912 TI - The prevalence and relevance of the Brugada-type electrocardiogram in the Danish general population: data from the Copenhagen City Heart Study. AB - AIMS: The prevalence of the Brugada-type electrocardiogram (ECG) in the Danish population is not known. METHODS AND RESULTS: Inhabitants from the city of Copenhagen, Denmark, have participated in a prospective study since 1976. Four cross-sectional surveys have been carried out. Follow-up was performed using public registers. At each examination, the participants had an ECG registered. ECGs, showing right bundle branch block (RBBB) were examined for a possible Brugada-type pattern. A total of 42,560 ECGs had been registered from 18,974 participants. 1,284 had been coded as RBBB. Among these ECGs, we found no ECGs showing type 1 Brugada pattern, and 14 showing type 2 or 3 pattern. The prevalence of the total number of ECGs with Brugada pattern was 7/10,000. None of the subjects with a Brugada-pattern ECG died suddenly during follow-up. CONCLUSION: The Brugada-type ECG pattern is rare in the general Danish population. None of the subjects with a Brugada-type ECG died suddenly during a follow-up of 6-33 years. PMID- 20356913 TI - Catheter ablation of a difficult accessory pathway guided by coronary sinus venography and 3D electroanatomical mapping. AB - A 38-year-old man with history of unsuccessful catheter ablation of paraseptal accessory pathway (AP) and cardiac arrest was referred for reablation. Coronary sinus (CS) venography and detailed three-dimensional electroanatomical mapping demonstrated a large diverticulum near the CS ostium. A single radiofrequency ablation at the neck of the diverticulum eliminated conduction in the AP completely. PMID- 20356914 TI - Spinal cord stimulation for refractory angina in patients implanted with cardioverter defibrillators: five case reports. AB - Patients implanted with a cardioverter defibrillator (ICD) who are suffering from refractory angina pectoris could benefit from spinal cord stimulation (SCS) due to the well-documented pain relieving effect. However, the combined treatment remains controversial. The aim of the study is to report successful long-term treatment with SCS in five patients implanted with cardioverter defibrillators. The combined treatments with ICD and thoracic epidural electrical stimulation were used in five patients with refractory angina pectoris. During the procedure of the implantation, testing with the maximal tolerable level of stimulation was carried out to exclude inference with the ICD. The following treatment with SCS has in all cases been successful, with significant pain relief and improved quality of life. There were no incidences of inappropriate defibrillator shocks. Spinal cord stimulation for refractory angina pectoris can be performed in patients implanted with cardioverter defibrillators without interference. However, individual testing during implantation or re-programming the devices is mandatory in order to assess optimal safety in each patient. PMID- 20356915 TI - Low-field magnetic resonance imaging: increased safety for pacemaker patients? AB - AIMS: The number of low-field (<0.5 T) magnetic resonance (MR) scanners installed worldwide is increasing due to a favourable cost and safety profile and improved patient comfort using an open-scanner design. Therefore, the aim of our study was to evaluate a strategy for the safe performance of magnetic resonance imaging (MRI) at a field strength of 0.2 T, in pacemaker (PM) patients without limitations on scan region, PM dependency, or the presence of abandoned leads. METHODS AND RESULTS: One hundred and fourteen PM patients, including PM-dependent patients and patients with abandoned leads, examined at a 0.2 T MR scanner due to an urgent clinical need for an MRI examination, were evaluated. All PMs were reprogrammed before MRI: if heart rate was <60 bpm, the asynchronous mode (with a rate of 80 bpm) was programmed to avoid MR-induced inhibition; if heart rate was >60 bpm, sense-only mode (ODO/OVO/OAO) was used to avoid MR-induced competitive pacing and potential proarrhythmia. Patients were monitored with electrocardiogram (ECG) and pulse oximetry. All PMs were interrogated before and after MRI, including measurement of lead impedance, pacing capture threshold (PCT), and battery voltage. All MRI scans were completed safely. No induction of arrhythmias or inhibition of PM output occurred. There were no statistically significant changes in lead impedance, PCT, or battery voltage (P>0.05). CONCLUSION: Low-field MRI of PM patients, including high-risk PM patients and MRI scan regions, can be performed with an acceptable risk-benefit ratio under controlled conditions. PMID- 20356916 TI - Pectus excavatum: review of therapeutic measures and case presentation. PMID- 20356917 TI - Pneumonia, anemia, and a positive Coombs test. PMID- 20356918 TI - Multiple-dose pharmacokinetics and safety of an ibuprofen-pseudoephedrine cold suspension in children. AB - Two studies were conducted to characterize multiple-dose pharmacokinetics and potential drug interactions of ibuprofen and pseudoephedrine combined in a suspension and to evaluate safety of this combination in children with common cold, flu, or sinusitis. In the pharmacokinetic study, 24 healthy children aged 4 11 years were administered ibuprofen -pseudoephedrine suspension at 7.5 and 1.125 mg/kg, respectively, every 6 hours for 5 doses. Serial blood samples were drawn over 6 hours after final dose for assessment of steady-state pharmacokinetics. In the open-label, multicenter safety study, more than 100 children aged 2-11 years experiencing symptomatic rhinitis were enrolled. Ibuprofen -pseudoephedrine suspension was administered as needed at similar mg/kg doses every 6-8 hours for up to 3 days. Subjects enrolled in the pharmacokinetic study showed no accumulation of either drug; their weight-adjusted clearances were independent of age, and results were comparable with those from previous single-ingredient studies. For ibuprofen, oral clearance (Cl/F) was 77.5 + or - 16.4 mL/kg/h and volume of distribution (Vd/F) was 0.147 + or - 0.037 L/kg. For pseudoephedrine, Cl/F was 12.3 + or - 2.2 mL/kg/min and Vd/F was 2.52 + or - 0.47 L/kg. In the safety study, adverse events were reported for 18.4% of subjects; most were mild to moderate intensity. There was little difference in incidence of adverse events among different age and weight groups. In conclusion, administration of combined ibuprofen and pseudoephedrine in children demonstrated similar pharmacokinetics when compared with reports of the pharmacokinetics for the single-ingredient products, consistent with no apparent drug interactions. The combination suspension was generally well tolerated. PMID- 20356919 TI - "Dyading" in the pediatric clinic improves access to care. AB - OBJECTIVE: This project evaluates the effect of "dyading" on pediatric outpatient care. METHODS: In "dyading," the medical assistant (MA) works with the provider in the exam room during the chart review, history taking, and patient education. In sequential care, the patient interacts with the MA, then the provider, then the MA again, with waiting in between. The authors measured visit time (from the MA starting with patient to the end of visit), the mean number of patients seen in a clinic session per provider, and patient satisfaction. RESULTS: After implementation of "dyading," mean visit time decreased from 37 + or - 14 to 25 + or - 11 minutes, the mean number of visits/session increased from 8.24 to 9.25, and waiting in the exam room reported by families decreased from 77% to 46%. CONCLUSIONS: "Dyading" decreased visit time, which increased the number of patients seen, thereby improving access to care. Patient time in the exam room decreased, which freed up exam rooms. PMID- 20356920 TI - Epstein Barr virus-associated acute acalculous cholecystitis: a rare occurrence but favorable outcome. PMID- 20356921 TI - Improving developmental screening in pediatric resident education. AB - OBJECTIVE: Given that pediatricians cite low competency in developmental screening, this study aims to effectively teach screening to residents. DESIGN: Using a quasi-experimental design, residents received an educational module and one-on-one teaching of 3 validated developmental screeners (Denver II, ASQ [Ages and Stages Questionnaire], and PEDS [Parents' Evaluation of Developmental Status]), with subsequent independent use with all 3 screeners with their own continuity patients. Outcome measures included changes in knowledge, skills, and preferences. RESULTS: All residents achieved significantly increased skills with all screeners. They strongly preferred the ASQ (70%), citing that this taught them normal (30.2%) and pathological (27.9%) development while negatively noting time (72.1%), scheduling issues (30.2%), and difficulties with child cooperation (20.9%). Knowledge specifics did not significantly increase. CONCLUSIONS: In depth developmental screening education revealed marked improvement in skills and preferences. These evaluations led to full adoption of the ASQ in resident clinics. Future research must test if effective development teaching in residency leads to increased routine screenings in practice. PMID- 20356922 TI - Natural disasters and mass-casualty events affecting children and families: a description of emergency preparedness and the role of the primary care physician. AB - OBJECTIVES: To determine the compliance of a select number of families with national recommendations for disaster preparedness. PATIENTS AND METHODS: A questionnaire focusing on knowledge of community evacuation plans and the presence of a family emergency response plan was distributed simultaneously in Dauphin County, Pennsylvania, and Bronx County, New York. RESULTS: A total of 1024 questionnaires were analyzed, and it was found that 35% (95% confidence interval [CI] = 32-38) of families were familiar with community evacuation plans, and 43% (95% CI = 40-46) had a family emergency response plan. Also, 17% (95% CI = 15-19) of respondents had discussed preparedness with their primary care physician; this subset of respondents was more likely to be familiar with community evacuation plans and was more likely to have a family emergency response plan. CONCLUSIONS: These data show that families are, for the most part, not in compliance with national recommendations for preparedness. Families who discussed preparedness with their primary care physician were more likely to be compliant. PMID- 20356923 TI - Lingual thyroid as a cause of primary hypothyroidism: congenital hypothyroidism in the neonatal period and beyond. PMID- 20356924 TI - Association of anxiety and depressive symptoms and adiposity among adolescent females, using dual energy X-ray absorptiometry. AB - The purpose of this study is to evaluate the association between anxiety and depressive symptoms and obesity among adolescent females using objective measures of adiposity and evaluate for moderating effects of race and age. This is a cross sectional analysis of 198 females aged 11, 13, 15, and 17 years (mean = 14.6, standard deviation = 2.2). Adiposity measures include BMI, BMI Z score, percentage body fat from dual energy X-ray absorptiometry (DXA), and fat distribution (fat mass upper vs lower body regions from DXA). Symptoms of anxiety are measured with the State-Trait Anxiety Inventory and depressive symptoms with the Children's Depression Inventory. Trait anxiety and depressive symptoms are positively associated with BMI and percentage body fat. No interaction of anxiety/ depressive symptoms with race or age on measures of adiposity was detected. Symptoms of anxiety and depression are associated with percentage body fat among adolescent females, linking psychological distress with a physiological measure of adiposity. PMID- 20356926 TI - N-linked glycosylation is required for optimal proteolytic activation of membrane bound transcription factor CREB-H. AB - CREB-H is a liver-enriched bZIP transcription factor of the CREB3 subfamily. CREB H is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain. Aberrant expression of CREB-H is implicated in liver cancer. In this study we characterized N-linked glycosylation of CREB-H in the luminal domain at the C-terminus. We found that CREB-H is modified at three N linked glycosylation sites in this region. Disruption of all three sites by site directed mutagenesis completely abrogated N-linked glycosylation of CREB-H. The unglycosylated mutant of CREB-H was not unstable, unfolded or aggregated. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A and KDEL-tailed site 1 protease, unglycosylated or deglycosylated CREB-H was largely uncleaved, retained in an inactive form in the endoplasmic reticulum, and less capable of activating transcription driven by unfolded protein response element or C-reactive protein promoter. Taken together, our findings suggest that N-linked glycosylation is required for full activation of CREB-H through intramembrane proteolysis. Our work also reveals a novel mechanism for the regulation of CREB-H-dependent transcription. PMID- 20356927 TI - Evidence that the tumor-suppressor protein BRCA2 does not regulate cytokinesis in human cells. AB - Germline mutations in the tumor-suppressor gene BRCA2 predispose to breast and ovarian cancer. BRCA2 plays a well-established role in maintaining genome stability by regulating homologous recombination. BRCA2 has more recently been implicated in cytokinesis, the final step of cell division, but the molecular basis for this remains unknown. We have used time-lapse microscopy, recently developed cytokinesis assays and BAC recombineering (bacterial artificial chromosome recombinogenic engineering) to investigate the function and localization of BRCA2 during cell division. Our analysis suggests that BRCA2 does not regulate cytokinesis in human cells. Thus, cytokinesis defects are unlikely to contribute to chromosomal instability and tumorigenesis in BRCA2-related cancers. PMID- 20356925 TI - Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14. AB - Podosomes are spot-like actin-rich structures formed at the ventral surface of monocytic and haematopoietic cells. Podosomes degrade extracellular matrix and are proposed to be involved in cell migration. A key question is whether podosomes form protrusions similar to the invadopodia of cancer cells. We characterised podosomes of immature dendritic cells using electron microscopy combined with both conventional and novel high-resolution structured illumination light microscopy. Dendritic cell podosomes are composed of actin foci surrounded by a specialised ring region that is rich in material containing paxillin. We found that podosomes were preferential sites for protrusion into polycarbonate filters impregnated with crosslinked gelatin, degrading up to 2 micrometers of matrix in 24 hours. Podosome-associated uptake of colloidal gold-labelled gelatin matrix appeared to occur via large phagosome-like structures or narrow tubular invaginations. The motor protein myosin-II was excluded from ring or core regions but was concentrated around them and the myosin-II inhibitor Blebbistatin reduced the length of podosome protrusions. Finally, we found that degradation, protrusion and endocytosis in this system are dependent on the matrix metalloproteinase MMP-14. We propose that podosomes mediate migration of dendritic cells through tissues by means of myosin-II-dependent protrusion coupled to MMP-14-dependent degradation and endocytosis. PMID- 20356928 TI - Activity of protein kinase CK2 uncouples Bid cleavage from caspase-8 activation. AB - In the present study, we quantitatively analysed the interface between apoptosis initiation and execution by determining caspase-8 activation, Bid cleavage and mitochondrial engagement (onset of mitochondrial depolarisation) in individual HeLa cervical cancer cells following exposure to tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Employing resonance-energy-transfer probes containing either the caspase-8 recognition site IETD or full-length Bid, we observed a significant delay between the times of caspase-8 activation and Bid cleavage, suggesting the existence of control steps separating these two processes. Subsequent analyses suggested that the divergence of caspase-8 activation and Bid cleavage are critically controlled by kinase signalling: inhibiting protein kinase CK2 by using 5,6-dichloro-l-(beta-D-ribofuranosyl-1) benzimidazole (DRB) or by overexpression of a dominant-negative CK2alpha catalytic subunit largely eliminated the lag time between caspase-8 activation and Bid cleavage. We conclude that caspase-8 activation and Bid cleavage are temporally uncoupled events, providing transient tolerance to caspase-8 activities. PMID- 20356929 TI - Breaking down the barriers: siRNA delivery and endosome escape. AB - RNA interference (RNAi)-based technologies offer an attractive strategy for the sequence-specific silencing of disease-causing genes. The application of small interfering (si)RNAs as potential therapeutic agents requires safe and effective methods for their delivery to the cytoplasm of the target cells and tissues. Recent studies have shown significant progress in the development of targeting reagents that facilitate the recognition of and siRNA delivery to specific cell types. However, most of these delivery approaches are not optimized to enable the intracellular trafficking of the siRNAs into the cytoplasm where they must associate with the RNA-induced silencing complex (RISC) to direct the cleavage of mRNAs bearing complementary binding sites. In particular, the trafficking of siRNAs from endosomes into the cytoplasm represents a major rate-limiting step for many delivery approaches. This Commentary focuses on novel strategies designed to enhance endosomal escape and thereby increase the efficacy of siRNA mediated gene silencing. PMID- 20356931 TI - Studies of association between LPIN1 variants and common metabolic phenotypes among 17,538 Danes. AB - OBJECTIVE: Lipin-1, encoded by LPIN1, is expressed in the major metabolically active tissues. Decreased expression of lipin-1 in adipose tissue correlates with increased insulin resistance, and tagging of the LPIN1 locus has shown that rs33997857, rs6744682, and rs6708316 associate with metabolic phenotypes, specifically body mass index (BMI) and fasting serum lipid levels, both on the individual single-nucleotide polymorphism level and with a three-marker haplotype. Our aim was to validate the reported findings in the Danish population. DESIGN: In the present study, variants were analyzed in LPIN1 using case-control studies, haplotype analyses, and quantitative trait analyses in a population of 17,538 Danes. METHODS: The three LPIN1 variants were genotyped in 17,538 Danes from four study populations of middle-aged people. This provided us with a statistical power >99% to replicate previous findings. Variants were analyzed individually and in haplotype combinations in studies of quantitative metabolic traits and in case-control studies. RESULTS: None of the three variants were associated with the examined quantitative traits including BMI, waist circumference, blood pressure, fasting serum lipid concentrations, or plasma glucose or serum insulin concentrations in the fasting state and following an oral glucose tolerance test. Haplotypes were tested for association with quantitative traits; however, only nominal association with blood pressure (P=0.04) and waist circumference (P=0.04) was observed. In case-control studies, no association was found for individual variants or the three-marker haplotype. CONCLUSION: LPIN1 rs33997857, rs6744682, and rs6708316 did not associate with type 2 diabetes, obesity, or related quantitative metabolic phenotypes in the Danish population examined. PMID- 20356932 TI - Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects. AB - AIMS: Low IGF1 levels have been associated with an increased cardiovascular risk. It is unknown however whether IGF1 mediates the atherosclerotic process by modulating high-density lipoprotein cholesterol (HDL-C) independently from confounders. To address this issue, we evaluated the association between IGF1 levels and HDL-C in nondiabetic subjects. METHODS: A cross-sectional analysis was used in the context of the CAtanzaro MEtabolic RIsk factors Study. One thousand and four participants (aged 20-69 years), for whom HDL-C and IGF1 measurements were available, were eligible for the study. RESULTS: After adjusting for gender and age, IGF1 levels were positively correlated with HDL-C, and negatively correlated with body mass index (BMI), waist circumference, blood pressure (BP), triglyceride, fasting insulin, and homeostasis model assessment (HOMA). In a logistic regression model adjusted for age and gender, IGF1 in the lowest tertile (<125 ng/ml) was associated with an increased risk of having low HDL-C (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.4-3.0; P=4x10(-5)) compared with the highest tertile (>186 ng/ml). When BMI, waist circumference, total cholesterol, triglyceride, and HOMA index were added to the model, IGF1 remained significantly associated with increased risk of low HDL-C (OR 1.52, 95% CI 1.01 2.31; P=0.04). A stepwise multivariate regression analysis in a model including age, gender, BMI, total cholesterol, triglycerides, IGF1, HOMA, and BP showed that the variables significantly associated with HDL-C were gender (P<0.0001), triglycerides (P<0.0001), total cholesterol (P<0.0001), BMI (P<0.0001), IGF1 levels (P<0.0001), and HOMA (P=0.001), accounting for 32.6% of its variation. CONCLUSIONS: These data provide evidence that IGF1 may be an independent modulator for HDL-C in nondiabetic individuals. PMID- 20356933 TI - The kidney in acromegaly: renal structure and function in patients with acromegaly during active disease and 1 year after disease remission. AB - BACKGROUND: The GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission. PATIENTS: Thirty acromegalic patients (15 males and 15 females), aged 32-70 years, were enrolled for the study. Ten de novo patients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls. RESULTS: In both active (A) and controlled (C) patients, creatinine clearance (P<0.001) and citrate (P<0.05) and oxalate levels (P<0.001) were higher, whereas filtered Na (P<0.001) and K (P<0.001) fractional excretions were lower than those in the controls. Urinary Ca (P<0.001) and Ph (P<0.05) levels were significantly increased compared with the controls, and in patients with disease control, urinary Ca (P<0.001) levels were significantly reduced compared with active patients. Microalbuminuria was significantly increased in active patients (P<0.05) compared with controlled patients and healthy control subjects. The longitudinal (P<0.05) and transverse (P<0.05) diameters of kidneys were significantly higher than those in the controls. In all patients, the prevalence of micronephrolithiasis was higher than that in the controls (P<0.001), and was significantly correlated to disease duration (r=0.871, P<0.001) and hydroxyproline values (r=0.639, P<0.001). CONCLUSIONS: The results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission. PMID- 20356930 TI - Prion-like disorders: blurring the divide between transmissibility and infectivity. AB - Prions are proteins that access self-templating amyloid forms, which confer phenotypic changes that can spread from individual to individual within or between species. These infectious phenotypes can be beneficial, as with yeast prions, or deleterious, as with mammalian prions that transmit spongiform encephalopathies. However, the ability to form self-templating amyloid is not unique to prion proteins. Diverse polypeptides that tend to populate intrinsically unfolded states also form self-templating amyloid conformers that are associated with devastating neurodegenerative disorders. Moreover, two RNA binding proteins, FUS and TDP-43, which form cytoplasmic aggregates in amyotrophic lateral sclerosis, harbor a 'prion domain' similar to those found in several yeast prion proteins. Can these proteins and the neurodegenerative diseases to which they are linked become 'infectious' too? Here, we highlight advances that define the transmissibility of amyloid forms connected with Alzheimer's disease, Parkinson's disease and Huntington's disease. Collectively, these findings suggest that amyloid conformers can spread from cell to cell within the brains of afflicted individuals, thereby spreading the specific neurodegenerative phenotypes distinctive to the protein being converted to amyloid. Importantly, this transmissibility mandates a re-evaluation of emerging neuronal graft and stem-cell therapies. In this Commentary, we suggest how these treatments might be optimized to overcome the transmissible conformers that confer neurodegeneration. PMID- 20356934 TI - GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome. AB - OBJECTIVE: GNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty. DESIGN: Longitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height. METHODS: Twenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed. RESULTS: In GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (P=0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (P=0.03 for both) as well as higher DHEAS and androstenedione levels (P=0.02 and P=0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively, P=0.04; 56 and 23.6% respectively, P=0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (P=0.03). CONCLUSIONS: In girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence. PMID- 20356935 TI - A longitudinal study of the impact of interviews on medical school admissions in Taiwan. AB - Medical schools in Taiwan have recently adopted the U.S. medical school admissions model by incorporating interviews into the selection process. The objective of this study was to investigate factors that contribute to successful medical school applications through the national entrance examination and interview admission routes. The sample consisted of survey data from five entry cohorts of medical students admitted to the National Yang-Ming University Faculty of Medicine from 2003 to 2007. Of the 513 students, 62% were admitted through the traditional national entrance examination route and 38% were admitted early after achieving a threshold score on the composite national exam followed by a structured interview. Students admitted through the interview route were more likely to be female, with an odds ratio (OR) of 2.17 (1.20-3.93). Maternal education level was an independent predictor of both early admission through a successful interview and higher medical school grade point average (GPA). Students admitted through the interview route had a 3.20 point higher first-year medical school GPA (p < .001) as determined by regression analyses. Those students who were admitted via interview did not have significantly different personality traits than those admitted through the traditional route. This study calls into question the ability of an admissions interview to select for noncognitive character traits. PMID- 20356936 TI - Has cytology become obsolete as a primary test in screening for cervical cancer? PMID- 20356937 TI - Has cytology become obsolete as a primary test in screening for cervical cancer? PMID- 20356938 TI - Moderately increased risks of Down's syndrome (1/51-1/270) identified on first trimester sequential screening: what do patients do with this information? AB - OBJECTIVE: To document patient decisions after being informed of a first trimester sequential screen Down's syndrome risk between 1/51 and 1/270. SETTING: A database analysis of sequential screen results for patients seen in the Philadelphia, PA (USA) area between January 2006 and March 2008 was examined. METHODS: All patients with first trimester sequential screen Down's syndrome risks in the 1/51-1/270 range were identified. Patient decisions regarding invasive testing (prior to completing the second trimester stage of the sequential screen), completion of the second trimester blood draw or no additional testing were tabulated. RESULTS: A total of 10,850 patients underwent first trimester sequential screening during this interval. Five hundred and fifty seven patients (5.1%) met the study inclusion criteria and had risks between 1/51 and 1/270. Ninety-three percent of these patients completed the sequential screening process before making any decisions regarding invasive testing. Four percent did not elect an invasive prenatal diagnosis procedure, but also did not complete the second trimester sequential screening blood draw and only 3.2% elected an invasive procedure based on their first trimester risk without completing the second trimester blood draw. Five women (0.9%) with low risks after the second stage screen chose to have an amniocentesis. CONCLUSION: The vast majority (97%) of patients in the moderately increased Down's syndrome risk range (1/51-1/270) following first trimester sequential screening did not pursue an invasive procedure based on their first trimester sequential screen risk. Using a > or = 1/50 risk cut-off in the first trimester is an effective screening policy for sequential screening. PMID- 20356939 TI - Distribution of nuchal translucency in antenatal screening for Down's syndrome. AB - OBJECTIVE: To determine whether the standard deviation of nuchal translucency (NT) measurements has decreased over time and if so to revise the estimate and assess the effect of revising the estimate of the standard deviation on the performance of antenatal screening for Down's syndrome. SETTING: Data from a routine antenatal screening programme for Down's syndrome comprising 106 affected and 22,640 unaffected pregnancies. METHODS: NT measurements were converted into multiple of the median (MoM) values and standard deviations of log(10) MoM values were calculated in affected and unaffected pregnancies. The screening performance of the Combined and Integrated tests (that include NT measurement) were compared using previous and revised estimates of the standard deviation. RESULTS: The standard deviation of NT in unaffected pregnancies has reduced over time (from 1998 to 2008) (e.g. from 0.1329 to 0.1105 [log(10) MoM] at 12-13 completed weeks of pregnancy, reducing the variance by about 30%). This was not observed in affected pregnancies. Compared with results from the serum, urine and ultrasound screening study (SURUSS), use of the revised NT standard deviations in unaffected pregnancies resulted in an approximate 20% decrease in the false-positive rate for a given detection rate; for example, from 2.1% to 1.7% (a 19% reduction) at a 90% detection rate using the Integrated test with first trimester markers measured at 11 completed weeks' gestation and from 4.4% to 3.5% (a 20% reduction) at an 85% detection rate using the Combined test at 11 completed weeks. CONCLUSIONS: The standard deviation of NT has declined over time and using the revised estimates improves the screening performance of tests that incorporate an NT measurement. PMID- 20356940 TI - Evaluation of a proposed mixture model to specify the distributions of nuchal translucency measurements in antenatal screening for Down's syndrome. AB - OBJECTIVES: A mixture model of crown-rump length (CRL)-dependent and CRL independent nuchal translucency (NT) measurements has been proposed for antenatal screening for Down's syndrome. We here compare the efficacy of the mixture model method with the standard method, which uses NT multiple of the median (MoM) values in a single distribution. Settings A routine antenatal screening programme for Down's syndrome comprising 104 affected and 22,284 unaffected pregnancies. METHODS: The ability of NT to distinguish between affected and unaffected pregnancies was compared using the mixture model method and the standard MoM method by using published distribution parameters for the mixture model of NT and parameters derived from these for the standard MoM method. The accuracy of the two methods was compared for NT and maternal age by comparing the median estimated risk with the prevalence of Down's syndrome in different categories of estimated risk. RESULTS: Using NT alone observed estimates of discrimination using the two methods are similar; at a 70% detection rate the false-positive rates were 12% using the mixture model method and 10% using the MoM method. Risk estimation was marginally (but not statistically significantly) more accurate using the standard MoM method. CONCLUSIONS: The mixture model method offers no advantage over the standard MoM method in antenatal screening for Down's syndrome, is more complicated and less generalizable to other data-sets. The standard MoM method remains the method of choice. PMID- 20356941 TI - Endorsement by the primary care practitioner consistently improves participation in screening for colorectal cancer: a longitudinal analysis. AB - OBJECTIVES: To investigate the effect of general practice (GP) and general practitioner (GPR) endorsement for faecal occult blood test (FOBT)-based screening on maintenance of participation in screening over four successive screening rounds. SETTING: South Australian residents aged > or = 50 years. METHODS: Random selection of four groups (n = 600 per group): one from the Commonwealth electoral roll (ER) and three from the combined patient lists of two collaborating GPs (GP1, GP2, GP3). Subjects were mailed offers to screen using a faecal immunochemical test over four successive rounds, spaced approximately 18 months apart. The GP1 and ER groups were invited to screen without any endorsement from a GPR or medical practice; GP2 invitees received an invitation indicating support for screening from their medical practice; and GP3 invitations were printed on practice letterhead and were signed by a GPR. RESULTS: Multivariate analyses indicated that initial participation as well as re participation over four successive rounds was significantly enhanced in the GP2 (39%, 42%, 45% and 44%) and GP3 groups (42%, 47%, 48% and 49%) relative to the ER group (33%, 37%, 40% and 36%). The analyses also indicated that 60-69 year olds were most likely to participate in all rounds (relative risk [RR] 1.49, 1.39, 1.43 and 1.25), and men were generally less likely to participate than women in all screening rounds (RR 0.86, 0.84, 0.80 and 0.83). CONCLUSIONS: Associating a GPR or medical practice of recent contact with an invitation to screen achieves better participation and re-participation than does an invitation from a centralized screening unit. Furthermore, enhanced participation can be achieved by practice endorsement alone without requiring actual GPR involvement. PMID- 20356942 TI - Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England. AB - OBJECTIVES: To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50-69 years. SETTING: The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50-69 years. METHODS: We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974-2004 and 1974-2003, respectively). We used Poisson regression for statistical inference. RESULTS: A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. CONCLUSIONS: The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case. PMID- 20356943 TI - Modelling the impact of changes in sensitivity on the outcomes of the UK breast screening programme. AB - OBJECTIVES: To assess the impact on breast cancer mortality of improving the sensitivity of breast screening programmes. METHODS: A Markov model was populated with data obtained from published statistics describing the UK National Health Service Breast Screening Programme and the incidence and mortality of breast cancer in the UK. The model was used to study the impact of changes to the sensitivity of screening. The effects on cancer detection rates and breast cancers and total mortality was studied for a cohort of women followed from age 45 to age 89. RESULTS: Running the model from age 45 to 89, with sensitivity set at the baseline value of 75%, predicts the detection at screening of 44 cancers per thousand of population and the detection outside screening of 82 cancers per thousand of population. Running the model with values of sensitivity from 75% to 95% shows the proportion of cancers detected at screening increasing as screening improves, and deaths from breast cancer falling. The drop in breast cancer deaths is however modest. Increasing sensitivity from 75% to 85% reduces the number of breast cancer deaths from 28 to 27 per thousand. CONCLUSIONS: Likely achievable improvements in the sensitivity of screening do not have a marked effect on breast cancer mortality. PMID- 20356944 TI - Randomized controlled trial of mammographic screening from age 40 ('Age' trial): patterns of screening attendance. AB - BACKGROUND: The Age trial was a randomized controlled trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41. Uptake of invitation to screening mammography in UK women aged below 50 is of interest, particularly in the light of the recent announcement that the national breast screening programme will begin inviting women from age 47. METHODS: The trial took place in 23 National Health Service breast screening units in England, Wales and Scotland between 1991 and 2004. Data on invitation and attendance during 13 years of trial fieldwork were analysed. The participants were 53,884 women in the intervention arm of the Age trial who were randomized to receive annual invitation to mammography from age 40 or 41 up to age 48. The trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151. RESULTS: Uptake of invitation to routine screening was 68% at first round and 69% at subsequent rounds. A total of 43,709 women in the intervention arm (81%) attended at least one routine screen and 23,262 (43%) attended at least seven screens; 31,392 women attended 75% or more of all routine invitations they were offered. Previous trial attendance was a predictor of subsequent uptake; attendance was inversely related to Townsend deprivation score. CONCLUSION: Uptake in this trial was comparable with that in the UK screening programme for women aged over 50. There was an inverse relationship between deprivation level and the number of screens attended. PMID- 20356945 TI - Perianal condylomas, anal squamous intraepithelial neoplasms and screening: a review of the literature. AB - Anal squamous intraepithelial lesions (ASILs) are the precursors to anal cancer. Human papillomavirus infection has a direct link to ASIL formation and is responsible for up to 80% of anal cancers. But while much importance has been focused on targeting cancer precursors in the cervix, relatively little concern has been afforded to the anal canal. With the advent of cervical Pap smear screening in various regions, the incidence of cervical cancer has declined. However, marked similarities in the biological and pathological profiles of cervical cancer and anal cancer mean that anal cancer should be preventable in the same way - by curbing the progression of ASIL to cancer. This article explores the literature on ASILs and the growing problem of anal cancer in the community, along with the literature surrounding the current progress towards implementing a screening programme for ASIL in the future. PMID- 20356946 TI - Prostate cancer incidence rates have started to decrease in central Italy. AB - The widespread use of prostate-specific antigen (PSA) testing has dramatically changed the epidemiology of prostate cancer. Growing incidence rates have been documented in almost all western countries following the increased usage of PSA screening. In the United States after a period of huge increase in incidence, rates have decreased to values lower than those of the pre-PSA era. Similar changes have been documented also in the area of the Tuscany Cancer Registry, central Italy, where prostate cancer incidence rates doubled from the early 1990s to 2003 and afterwards decreased. This is the first evidence, to our knowledge, of a decline in prostate cancer incidence in Italy following the screening related increase. PMID- 20356948 TI - Some women may not want cervical screening. PMID- 20356949 TI - Effects of Monascus-fermented rice extract on malignant cell-associated neovascularization and intravasation determined using the chicken embryo chorioallantoic membrane model. AB - The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose- and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% +/- 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy. PMID- 20356950 TI - Communication in cancer care: discussing complementary and alternative medicine. AB - In recent years, there has been an increased interest in complementary and alternative medicine (CAM) use among people with cancer. Many are looking for informed advice and desire communication with their physicians about CAM use. Communication is crucial in establishing trust with patients, gathering information, addressing patient emotions, and assisting patients in decisions about care. The quality of communication in cancer care has been shown to affect patient satisfaction, decision making, patient distress and well-being, compliance, and even malpractice litigation. Communication is now recognized as a core clinical skill in medicine, including cancer care, and is important to the delivery of high-quality care. A communication approach that fosters a collaborative relationship that includes adequate information exchange, responds to emotional needs, and manages uncertainty can lead to informed decisions about CAM use. This type of communication can help facilitate an open discussion with cancer patients and their families about integrating CAM use into their care and help physicians fulfill their roles in caring, comforting, and healing, even when cure is not possible. In this article, the authors discuss a possible model of effective patient-physician communication about CAM use in cancer care based on a comprehensive overview of the literature. PMID- 20356951 TI - Chemoprotective effects of Zataria multiflora against genotoxicity induced by cyclophosphamide in mice bone marrow cells. AB - The preventive effective of Zataria multiflora (ZM) extract was investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide (CP). Mice were orally (gavaged) pretreated with solutions of ZM extract prepared at 3 different doses (50, 100, and 200 mg/kg body weight) for 7 consecutive days. They were injected with CP (50 mg/kg body weight) on the seventh day of treatment and killed after 24 hours for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of PCE/(PCE + NCE), where PCE refers to polychromatic erythrocyte, and NCE refers to normochromatic erythrocyte. All 3 doses of extract significantly reduced MnPCEs induced by CP (P < .0001). Zataria extract at a dose of 200 mg/kg body weight reduced MnPCEs 7.8 fold and also completely normalized the PCE/ (PCE + NCE) ratio. Administration of ZM inhibited bone marrow suppression induced by CP. Zataria extract exhibited concentration dependent antioxidant activity on 1, 1-diphenyl 2-picryl hydrazyl free radical and lipid peroxidation. It appeared that ZM with antioxidative activity reduced the oxidative stress and genotoxicity induced by CP in mouse bone marrow cells. PMID- 20356952 TI - Plant Fe status affects the composition of siderophore-secreting microbes in the rhizosphere. AB - BACKGROUND AND AIMS: Soil microbes have been demonstrated to play an important role in favouring plant iron (Fe) uptake under Fe-limiting conditions. However, the mechanisms involved are still unclear. This present study reported the effects of plant Fe status on the composition of siderophore-secreting microbes in the rhizosphere, and their potential function in improving plant Fe nutrition. METHODS: An Fe-efficient plant, red clover (Trifolium pratense 'Kenland') was cultured in a calcareous soil to obtain rhizosphere soils with (Fe-sufficient) or without (Fe-stressed) foliar FeEDTA spraying. The siderophore-producing ability of rhizospheric microbes was measured. The bioavailability of the siderophore solubilized Fe from iron oxides/hydroxides was tested in hydroponic culture. KEY RESULTS: In rhizosphere soil, the number of microbes that secreted siderophores quickly was more in the Fe-stressed treatment than in the Fe-sufficient one, while the number of microbes that did not secret siderophores was the opposite. A significantly higher concentration of phenolics was detected in the rhizosphere soil of Fe-stressed plants. Moreover, after the soil was incubated with phenolic root exudates, the composition of the siderophore-secreting microbial community was similar with that of the rhizosphere of Fe-stressed plant. Additionally, the siderophores produced by a rhizospheric microbe isolated from the Fe-stressed treatment can well solubilize iron oxides/hydroxides, and the utilization of the siderophore-solubilized Fe by plant was even more efficient than EDTA-Fe. CONCLUSIONS: Iron-deficiency stress of red clover would alter the composition of siderophore-secreting microbes in the rhizosphere, which is probably due to the phenolics secretion of the root, and may in turn help to improve the solubility of Fe in soils and plant Fe nutrition via elevated microbial siderophore secretion. PMID- 20356953 TI - Occurrence of adventitious sprouting in short-lived monocarpic herbs: a field study of 22 weedy species. AB - BACKGROUND AND AIMS: Adventitious sprouting from the hypocotyle and roots in monocarpic herbs has been confirmed in previous experimental studies as a means to avoid bud limitation after severe injury in annual and biennial plants. Data regarding the role of adventitious sprouting in natural populations, however, were lacking. The aim of the present study was to assess whether adventitious sprouting occurs in natural populations and how it is affected by plant size, plant injury, plant cover and environmental characteristics. METHODS: Data were sampled from 14 037 individual plants from 389 populations belonging to 22 annual and biennial species. Growth parameters were measured in individual plants, species composition and plant cover in communities were evaluated, and environmental characteristics were estimated using Ellenberg indicator values. KEY RESULTS: It was confirmed that adventitious sprouting occurs in natural populations of all but five species examined. Adventitious sprouting was positively affected by plant size and plant injury. Environmental factors including availability of soil nitrogen were not shown to affect adventitious sprouting. Annual and biennial plants did not differ in sprouting, but upright annuals had a lower number of and longer adventitious shoots than prostrate annuals. CONCLUSIONS: Adventitious bud formation is used to overcome meristem limitation when stem parts are lost due to injury, and thus resprouting in short lived monocarps should not be overlooked. PMID- 20356954 TI - JACKDAW controls epidermal patterning in the Arabidopsis root meristem through a non-cell-autonomous mechanism. AB - In Arabidopsis, specification of the hair and non-hair epidermal cell types is position dependent, in that hair cells arise over clefts in the underlying cortical cell layer. Epidermal patterning is determined by a network of transcriptional regulators that respond to an as yet unknown cue from underlying tissues. Previously, we showed that JACKDAW (JKD), a zinc finger protein, localizes in the quiescent centre and the ground tissue, and regulates tissue boundaries and asymmetric cell division by delimiting SHORT-ROOT movement. Here, we provide evidence that JKD controls position-dependent signals that regulate epidermal-cell-type patterning. JKD is required for appropriately patterned expression of the epidermal cell fate regulators GLABRA2, CAPRICE and WEREWOLF. Genetic interaction studies indicate that JKD operates upstream of the epidermal patterning network in a SCRAMBLED (SCM)-dependent fashion after embryogenesis, but acts independent of SCM in embryogenesis. Tissue-specific induction experiments indicate non-cell-autonomous action of JKD from the underlying cortex cell layer to specify epidermal cell fate. Our findings are consistent with a model where JKD induces a signal in every cortex cell that is more abundant in the hair cell position owing to the larger surface contact of cells located over a cleft. PMID- 20356955 TI - FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation. AB - FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. We show that TLE2 is co expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C terminal YWPMSPF motif. Although direct binding seems to be mediated by the N terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon. PMID- 20356956 TI - Ets1 is required for proper migration and differentiation of the cardiac neural crest. AB - Defects in cardiac neural crest lead to congenital heart disease through failure of cardiac outflow tract and ventricular septation. In this report, we demonstrate a previously unappreciated role for the transcription factor Ets1 in the regulation of cardiac neural crest development. When bred onto a C57BL/6 genetic background, Ets1(-/-) mice have a nearly complete perinatal lethality. Histologic examination of Ets1(-/-) embryos revealed a membranous ventricular septal defect and an abnormal nodule of cartilage within the heart. Lineage tracing experiments in Ets1(-/-) mice demonstrated that cells of the neural crest lineage form this cartilage nodule and do not complete their migration to the proximal aspects of the outflow tract endocardial cushions, resulting in the failure of membranous interventricular septum formation. Given previous studies demonstrating that the MEK/ERK pathway directly regulates Ets1 activity, we cultured embryonic hearts in the presence of the MEK inhibitor U0126 and found that U0126 induced intra-cardiac cartilage formation, suggesting the involvement of a MEK/ERK/Ets1 pathway in blocking chondrocyte differentiation of cardiac neural crest. Taken together, these results demonstrate that Ets1 is required to direct the proper migration and differentiation of cardiac neural crest in the formation of the interventricular septum, and therefore could play a role in the etiology of human congenital heart disease. PMID- 20356958 TI - A direct method for air kerma-length product measurement in CT for verification of dose display calibrations. AB - The dose display values of computed tomography (CT) devices are used for patient dose estimation and as a tool for optimisation. Therefore, the dose display value accuracy should be verified. In practice, this means doing measurements in the standard phantoms and comparing results with the dose display values. The traditional method for measuring CT dose enables measurements only for one axial rotation, and there has not been a method for measuring the dose of a complete helical scan sequence. In this work, a new method for a direct measurement of the dose of a complete helical sequence is developed and tested. Results show that this method is practical and that the accuracy of the modern CT devices seems to be at the sufficient level, so that the dose display values can be used for patient dose estimation. PMID- 20356957 TI - Mesodermal Wnt signaling organizes the neural plate via Meis3. AB - In vertebrates, canonical Wnt signaling controls posterior neural cell lineage specification. Although Wnt signaling to the neural plate is sufficient for posterior identity, the source and timing of this activity remain uncertain. Furthermore, crucial molecular targets of this activity have not been defined. Here, we identify the endogenous Wnt activity and its role in controlling an essential downstream transcription factor, Meis3. Wnt3a is expressed in a specialized mesodermal domain, the paraxial dorsolateral mesoderm, which signals to overlying neuroectoderm. Loss of zygotic Wnt3a in this region does not alter mesoderm cell fates, but blocks Meis3 expression in the neuroectoderm, triggering the loss of posterior neural fates. Ectopic Meis3 protein expression is sufficient to rescue this phenotype. Moreover, Wnt3a induction of the posterior nervous system requires functional Meis3 in the neural plate. Using ChIP and promoter analysis, we show that Meis3 is a direct target of Wnt/beta-catenin signaling. This suggests a new model for neural anteroposterior patterning, in which Wnt3a from the paraxial mesoderm induces posterior cell fates via direct activation of a crucial transcription factor in the overlying neural plate. PMID- 20356963 TI - An agitated young man. PMID- 20356960 TI - Immunocompromised patient with an ulcerated nasolabial skin lesion. PMID- 20356959 TI - How the brain handles temporally uncoupled bimanual movements. AB - Whereas the cerebral representation of bimanual spatial coordination has been subject to prior research, the networks mediating bimanual temporal coordination are still unclear. The present study used functional imaging to investigate cerebral networks mediating temporally uncoupled bimanual finger movements. Three bimanual tasks were designed for the execution of movements with different timing and amplitude, with same timing but different amplitude, and with same timing and amplitude. Functional magnetic resonance imaging results showed an increase of activation within right premotor and dorsolateral prefrontal, bilateral inferior parietal, basal ganglia, and cerebellum areas related to temporally uncoupled bilateral finger movements. Further analyses showed a decrease of connectivity between homologous primary hand motor regions. In contrast, there was an increase of connectivity between motor regions and anterior cingulate, premotor and posterior parietal regions during bimanual movements that were spatially or both temporally and spatially uncoupled, compared with bimanual movements that were both spatially and temporally coupled. These results demonstrate that the extent of bihemispheric coupling of M1 areas is related to the degree of temporal synchronization of bimanual finger movements. Furthermore, inferior parietal and premotor regions play a key role for the implementation not only of spatial but also of temporal movement parameters in bimanual coordination. PMID- 20356967 TI - Home secretary bans mephedrone after taking advice from depleted council. PMID- 20356970 TI - Quality of stroke care varies widely across England. PMID- 20356974 TI - Breast screening benefits twice as many women as it harms, shows new analysis. PMID- 20356975 TI - New guidance allows donors to name who receives their organs when they die. PMID- 20356977 TI - Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. AB - The prognosis for women with breast cancer is adversely affected by the comorbidities of obesity and diabetes mellitus (DM), which are conditions associated with elevated levels of circulating fatty acids, hyperglycaemia and hyperinsulinaemia. We investigated the effects of exposure of non-malignant and malignant human breast epithelial cells to elevated levels of fatty acids and glucose on their growth, survival and response to chemotherapeutic agents. We found that palmitate induced cell death in the non-malignant cells but not in the malignant cells, which was abrogated through the inhibition of ceramide production and by oleate but not by IGF1. Fatty acid synthase (FAS) is responsible for the de novo synthesis of fatty acids from sugars, and is over expressed in many epithelial cancers. Abundance of FAS was higher in malignant cells than in non-malignant cells, and was up-regulated by IGF1 in both cell types. IGF-induced growth of non-malignant cells was unaffected by suppression of FAS expression, whereas that of malignant cells was blocked as was their resistance to palmitate-induced cell death. Palmitate did not affect cell proliferation, whereas oleate promoted the growth of non-malignant cells but had the opposite effect, that is, inhibition of IGF1-induced growth of malignant cells. However, when the phosphatidylinositol 3-kinase pathway was inhibited, oleate enhanced IGF1-induced growth in both cell types. Hyperglycaemia conferred resistance on malignant cells, but not on non-malignant cells, to chemotherapy induced cell death. This resistance was overcome by inhibiting FAS or ceramide production. Understanding the mechanisms involved in the associations between obesity, DM and breast cancer may lead to more effective treatment regimens and new therapeutic targets. PMID- 20356978 TI - Crystal-storing histiocytosis with renal Fanconi syndrome: pathological and molecular characteristics compared with classical myeloma-associated Fanconi syndrome. AB - BACKGROUND: Crystal-storing histiocytosis (CSH) is a poorly described complication of monoclonal gammopathy featuring histiocyte lysosomal storage of kappa light chain (kappa LC) crystals. Although CSH is usually associated with systemic manifestations, renal involvement is uncommon. METHODS: To investigate the molecular mechanisms implicated in kappa LC crystallization, we performed immunopathological and molecular studies in three patients with CSH and renal Fanconi syndrome (CSH/FS). The V kappa sequences were determined, and resulting molecular models were compared with previously reported myeloma-associated FS kappa LC sequences. RESULTS: All patients presented with chronic tubulo interstitial nephritis and renal FS with accumulation of monoclonal kappa LC crystals within proximal tubular cells. They showed peri-renal and interstitial infiltration by histiocytes containing eosinophilic crystalline inclusions (pseudo-pseudo-Gaucher cells). LC sequences were determined and assigned to their germline counterparts, in strong homology with previously reported myeloma associated FS sequences. Comparison of CSH/FS V kappa domain 3D structures with the germline-encoded structures and those from patients with myeloma-associated FS underlined distinct hydrophobic residues exposed to the solvent in two patients, likely favouring the formation of a variant form of crystals that may further resist degradation after phagocytosis. CONCLUSION: Although CSH/FS and myeloma-associated FS are closely related disorders, peculiar mutations in the V domains of CSH/FS monoclonal kappa LCs, different from those in myeloma associated FS, may account for crystal morphology, predominant accumulation within histiocytes and multiple organ involvement in CSH. PMID- 20356979 TI - The reliability of pre-transplant donor renal biopsies (PTDB) in predicting the kidney state. A comparative single-centre study on 154 untransplanted kidneys. AB - BACKGROUND: Pre-transplant donor biopsy (PTDB) is a common practice in marginal donors, taking for granted that it represents the whole kidney state, but its reliability has not yet been thoroughly investigated. This prompted us to carry out a comparative study on a needle biopsy group (NBG) and a wedge biopsy group (WBG) and their corresponding untransplanted kidneys. METHODS: One hundred and fifty-four biopsies and matched kidneys were scored for four morphologic indexes, i.e. tubular atrophy, interstitial fibrosis, vascular damage and global glomerulosclerosis. Categorical indexes were statistically evaluated for concordance with the k index, and the percentage of sclerotic glomeruli with correlation and linear regression analysis. RESULTS: Agreement between biopsies and kidneys was similar in both NBG and WBG with high scores for vascular damage (k 0.74 and 0.75) and intermediate ones for tubular atrophy (k 0.54 and 0.50). Agreement as to fibrosis and glomerular sclerosis was intermediate in the WBG (k 0.56 and 0.55) and poor in the NBG (k 0. 34 and 0.18). Vascular damage was underscored and glomerulosclerosis overscored in both groups, whereas interstitial fibrosis was underscored in the NBG and overscored in WBG. The agreement for the total score, i.e. the sum of the single indexes, was high in the NBG (k 0.73) and intermediate in WBG (k 0.57). Agreement for glomerulosclerosis and total score rose consistently in both groups along with the increasing number of biopsy glomeruli. There was an agreement as to biopsy and kidney evaluation for fitness for transplantation in 85% of NBG and 81% of WBG. CONCLUSIONS: PTDB supplies reliable data on the actual kidney state, with better results for needle biopsy. Although the biopsy size plays a role, samples with over 10 glomeruli suffice for clinical purposes. Vascular damage is the most faithful single parameter, whereas global glomerulosclerosis estimation requires some caution. PMID- 20356980 TI - What underlies the perception that a medical intervention is effective? An exploratory study among smokers. AB - INTRODUCTION: The perceived ineffectiveness of medical interventions is a key predictor of their underuse. This study explores the nature of this perception with regards to a range of medical interventions. METHODS: Adult smokers (n = 18) completed interviews and questionnaires using the repertory grid technique to elicit personal constructs underlying perceptions of effectiveness of a range of medical interventions (three to stop smoking, three to prevent heart disease, one to reduce pain, one to lose weight, and one to treat depression). Principle components analysis was applied to identify the key underlying dimensions within the constructs. Numerical estimates of the effectiveness of the interventions were also collected from participants to compare them with the published evidence. RESULTS: Constructs clustered around three dimensions: "therapeutic impact," "behavior-dependent impact," and "impact facilitates general health." Smokers perceived impacts that are dependent on the individuals' behavior to offer small therapeutic impacts, while facilitating individuals' general health. These three characteristics were attributed to nonbiomedical interventions (e.g., talk-based interventions), while the opposite characteristics were attributed to biomedical interventions (i.e., medication and surgery). Numerical estimates showed that the effectiveness of stop-smoking interventions was underestimated relative to interventions to prevent heart disease. DISCUSSION: The elicited dimensions provide a basis for communicating evidence concerning the effectiveness of medical interventions, with a view to increasing their use. PMID- 20356981 TI - Lung cancer: multidisciplinary approach for management: cell and molecular biology assembly contribution to the celebration of 20 years of the ERS. PMID- 20356982 TI - Continuing medical education across Europe: the role of EBAP and the ERS in facing the challenges of life-long learning. PMID- 20356983 TI - End-tidal CO2 for exclusion of suspected pulmonary embolism: a new partner for Wells? PMID- 20356984 TI - Ventilator-associated pneumonia: approaching the horizon. PMID- 20356985 TI - Idiopathic pulmonary fibrosis and pirfenidone. PMID- 20356986 TI - Asthma and pulmonary arterial hypertension: do they share a key mechanism of pathogenesis? AB - Although largely distinct and seemingly unrelated, asthma and pulmonary arterial hypertension (PAH) have important pathological features in common, including inflammation, smooth muscle contraction and remodelling. We hypothesised that these common features could be explained by one shared mechanism of pathogenesis: activation of the transcription factor NFAT (nuclear factor of activated T cells). If this concept is validated, it could lead to the introduction of novel therapeutic strategies against both lung disorders. In several experimental models, airway remodelling is accompanied by remodelling of smaller pulmonary arteries, validating the hypothesis of their similar pathogenesis. In addition, lungs of vasoactive intestinal peptide (VIP) knockout mice express airway hyperresponsiveness with airway inflammation and PAH with vascular remodelling, with both sets of pathological findings being reversible with VIP treatment. Preliminary data suggest that absence of the VIP gene leads to activation of the calcineurin-NFAT pathway, and that VIP is probably a physiological inhibitor of this pathway. Enough evidence exists to support the views that asthma and PAH share important pathological features, probably related to NFAT activation, and that VIP may be a physiological modulator of this mechanism. PMID- 20356987 TI - YKL-40 in asthmatic patients, and its correlations with exacerbation, eosinophils and immunoglobulin E. AB - The chitinase-like protein YKL-40, which binds chitin but lacks chitinase activity, has been found to be either the cause or a biomarker for asthma. The aim of our study was to investigate whether serum YKL-40 levels are increased in Chinese patients with asthma and identify its correlation to acute exacerbation, total serum immunoglobulin (Ig)E, the percentage of peripheral blood eosinophils and lung function. We quantified serum YKL-40 levels, total IgE levels and peripheral blood eosinophil percentages in patients with asthma, as well as in controls from the communities surrounding our hospital. The lung function of asthma subjects was also measured. Our data showed that the serum YKL-40 levels were significantly elevated in patients with asthma compared with controls and, when the asthma subjects were stratified, serum YKL-40 levels in the exacerbation group were higher than those in the stable and control groups. In addition, serum YKL-40 levels correlated positively with total serum IgE levels and the percentage of peripheral blood eosinophils, but correlated inversely with lung functions. Thus, we conclude that YKL-40 is found in increased quantities in the serum of Chinese patients with asthma, and its level correlates with exacerbation attacks, indicating that high levels of serum YKL-40 may be a biological characteristic of the exacerbation of asthma. PMID- 20356988 TI - Cognitive function in COPD. AB - In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function. Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD. Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function. PMID- 20356989 TI - Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension. PMID- 20356990 TI - Levels of soluble human leukocyte antigen-G are increased in asthmatic airways. PMID- 20356991 TI - Pneumocystis pneumonia in an HIV-negative patient with no overt risk factors on presentation. PMID- 20356992 TI - Unusual treatment of patent foramen ovale after pneumonectomy. PMID- 20356993 TI - How to treat children's pneumonia: a complex problem. PMID- 20356994 TI - Endocrinological derangement in COPD. PMID- 20356996 TI - Pre-operative evaluation of lung function test results. PMID- 20356997 TI - Assessment of linezolid efficacy and safety in MDR- and XDR-TB: an Indian perspective. PMID- 20356998 TI - The online Cough Clinic. PMID- 20356999 TI - The online Cough Clinic. PMID- 20357000 TI - The hydrophobic core of the Sec61 translocon defines the hydrophobicity threshold for membrane integration. AB - The Sec61 translocon mediates the translocation of proteins across the endoplasmic reticulum membrane and the lateral integration of transmembrane segments into the lipid bilayer. The structure of the idle translocon is closed by a lumenal plug domain and a hydrophobic constriction ring. To test the function of the apolar constriction, we have mutated all six ring residues of yeast Sec61p to more hydrophilic, bulky, or even charged amino acids (alanines, glycines, serines, tryptophans, lysines, or aspartates). The translocon was found to be surprisingly tolerant even to the charge mutations in the constriction ring, because growth and translocation efficiency were not drastically affected. Most interestingly, ring mutants were found to affect the integration of hydrophobic sequences into the lipid bilayer, indicating that the translocon does not simply catalyze the partitioning of potential transmembrane segments between an aqueous environment and the lipid bilayer but that it also plays an active role in setting the hydrophobicity threshold for membrane integration. PMID- 20357001 TI - Regulation of lens gap junctions by Transforming Growth Factor beta. AB - Gap junction-mediated intercellular communication (GJIC) is essential for the proper function of many organs, including the lens. GJIC in lens epithelial cells is increased by FGF in a concentration-dependent process that has been linked to the intralenticular gradient of GJIC required for lens transparency. Unlike FGF, elevated levels of TGF-beta are associated with lens dysfunction. We show that TGF-beta1 or -2 up-regulates dye coupling in serum-free primary cultures of chick lens epithelial cells (dissociated cell-derived monolayer cultures [DCDMLs]) via a mechanism distinct from that utilized by other growth factors. Remarkably, the ability of TGF-beta and of FGF to up-regulate GJIC is abolished if DCDMLs are simultaneously exposed to both factors despite undiminished cell-cell contact. This reduction in dye coupling is attributable to an inhibition of gap junction assembly. Connexin 45.6, 43, and 56-containing gap junctions are restored, and intercellular dye coupling is increased, if the activity of p38 kinase is blocked. Our data reveal a new type of cross-talk between the FGF and TGF-beta pathways, as well as a novel role for TGF-beta and p38 kinase in the regulation of GJIC. They also provide an explanation for how pathologically increased TGF beta signaling could contribute to cataract formation. PMID- 20357003 TI - A domesticated piggyBac transposase plays key roles in heterochromatin dynamics and DNA cleavage during programmed DNA deletion in Tetrahymena thermophila. AB - Transposons comprise large fractions of eukaryotic genomes and provide genetic reservoirs for the evolution of new cellular functions. We identified TPB2, a homolog of the piggyBac transposase gene that is required for programmed DNA deletion in Tetrahymena. TPB2 was expressed exclusively during the time of DNA excision, and its encoded protein Tpb2p was localized in DNA elimination heterochromatin structures. Notably, silencing of TPB2 by RNAi disrupts the final assembly of these heterochromatin structures and prevents DNA deletion to occur. In vitro studies revealed that Tpb2p is an endonuclease that produces double strand breaks with four-base 5' protruding ends, similar to the ends generated during DNA deletion. These findings suggest that Tpb2p plays a key role in the assembly of specialized DNA elimination chromatin architectures and is likely responsible for the DNA cleavage step of programmed DNA deletion. PMID- 20357002 TI - Arf3 is activated uniquely at the trans-Golgi network by brefeldin A-inhibited guanine nucleotide exchange factors. AB - It is widely assumed that class I and II Arfs function interchangeably throughout the Golgi complex. However, we report here that in vivo, Arf3 displays several unexpected properties. Unlike other Golgi-localized Arfs, Arf3 associates selectively with membranes of the trans-Golgi network (TGN) in a manner that is both temperature-sensitive and uniquely dependent on guanine nucleotide exchange factors of the BIGs family. For example, BIGs knockdown redistributed Arf3 but not Arf1 from Golgi membranes. Furthermore, shifting temperature to 20 degrees C, a temperature known to block cargo in the TGN, selectively redistributed Arf3 from Golgi membranes. Arf3 redistribution occurred slowly, suggesting it resulted from a change in membrane composition. Arf3 knockdown and overexpression experiments suggest that redistribution is not responsible for the 20 degrees C block. To investigate in more detail the mechanism for Arf3 recruitment and temperature-dependent release, we characterized several mutant forms of Arf3. This analysis demonstrated that those properties are readily separated and depend on pairs of residues present at opposite ends of the protein. Furthermore, phylogenetic analysis established that all four critical residues were absolutely conserved and unique to Arf3. These results suggest that Arf3 plays a unique function at the TGN that likely involves recruitment by a specific receptor. PMID- 20357004 TI - RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin. AB - We report on the characterization of RNF-121, an evolutionarily conserved E3 ligase RING finger protein that is expressed in the endoplasmic reticulum (ER) of various cells and tissues in Caenorhabditis elegans. Inactivation of RNF-121 induced an elevation in BiP expression and increased the sensitivity of worms to ER stress. Genetic analysis placed RNF-121 downstream of the unfolded protein response (UPR) regulator protein kinase-like endoplasmic reticulum kinase (PERK). We identify PAT-3::GFP, the beta subunit of the heterodimeric integrin receptors, as an RNF-121 substrate; whereas induction of RNF-121 expression reduced the level of PAT-3::GFP in the gonad distal tip cells, inhibition of RNF-121 led to the accumulation of stably bound PAT-3::GFP inclusions. Correspondingly, overexpression of RNF-121 during early stages of gonad development led to aberrations in germline development and gonad migration that overlap with those observed after PAT-3 inactivation. The formation of these gonad abnormalities required functional ER-associated degradation (ERAD) machinery. Our findings identify RNF-121 as an ER-anchored ubiquitin ligase that plays a specific role in the ERAD pathway by linking it to the regulation of the cell adhesion integrin receptors. PMID- 20357005 TI - Mitf induction by RANKL is critical for osteoclastogenesis. AB - Microphthalmia-associated transcription factor (Mitf) regulates the development and function of several cell lineages, including osteoclasts. In this report, we identified a novel mechanism by which RANKL regulates osteoclastogenesis via induction of Mitf isoform E (Mitf-E). Both Mitf-A and Mitf-E are abundantly present in osteoclasts. Unlike Mitf-A, which is ubiquitously expressed and is present in similar amounts in macrophages and osteoclasts, Mitf-E is almost nondetectable in macrophages, but its expression is significantly up-regulated during osteoclastogenesis. In addition to their different expression profiles, the two isoforms are drastically different in their abilities to support osteoclastogenesis, despite sharing all known functional domains. Unlike Mitf-A, small amounts of Mitf-E are present in nuclear lysates unless chromatin is digested/sheared during the extraction. Based on these data, we propose a model in which Mitf-E is induced during osteoclastogenesis and is closely associated with chromatin to facilitate its interaction with target promoters; therefore, Mitf-E has a stronger osteoclastogenic activity. Mitf-A is a weaker osteoclastogenic factor, but activated Mitf-A alone is not sufficient to fully support osteoclastogenesis. Therefore, this receptor activator for nuclear factor kappaB ligand (RANKL)-induced Mitf phenomenon seems to play an important role during osteoclastogenesis. Although the current theory indicates that Mitf and its binding partner Tfe3 are completely redundant in osteoclasts, using RNA interference, we demonstrated that Mitf has a distinct role from Tfe3. This study provides the first evidence that RANKL-induced Mitf is critical for osteoclastogenesis and Mitf is not completely redundant with Tfe3. PMID- 20357006 TI - Activation of the mitogen-activated protein kinase, Slt2p, at bud tips blocks a late stage of endoplasmic reticulum inheritance in Saccharomyces cerevisiae. AB - Inheritance of the endoplasmic reticulum (ER) requires Ptc1p, a type 2C protein phosphatase of Saccharomyces cerevisiae. Genetic analysis indicates that Ptc1p is needed to inactivate the cell wall integrity (CWI) MAP kinase, Slt2p. Here we show that under normal growth conditions, Ptc1p inactivates Slt2p just as ER tubules begin to spread from the bud tip along the cortex. In ptc1Delta cells, the propagation of cortical ER from the bud tip to the periphery of the bud is delayed by hyperactivation of Slt2p. The pool of Slt2p that controls ER inheritance requires the CWI pathway scaffold, Spa2p, for its retention at the bud tip, and a mutation within Slt2p that prevents its association with the bud tip blocks its role in ER inheritance. These results imply that Slt2p inhibits a late step in ER inheritance by phosphorylating a target at the tip of daughter cells. The PI4P5-kinase, Mss4p, is an upstream activator of this pool of Slt2p. Ptc1p-dependant inactivation of Slt2p is also needed for mitochondrial inheritance; however, in this case, the relevant pool of Slt2p is not at the bud tip. PMID- 20357007 TI - Keratin 8/18 modulation of protein kinase C-mediated integrin-dependent adhesion and migration of liver epithelial cells. AB - Keratins are intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatocyte and hepatoma cell IFs are made solely of keratins 8/18 (K8/K18), the hallmark of all simple epithelia. Cell attachment/spreading (adhesion) and migration involve the formation of focal adhesions at sites of integrin interactions with extracellular matrix, actin adaptors such as talin and vinculin, and signaling molecules such as focal adhesion kinase (FAK) and member(s) of the protein kinase C (PKC) family. Here, we identify the novel PKCdelta as mediator of the K8/K18 modulation of hepatoma cell adhesion and migration. We also demonstrate a K8/K18-dependent relationship between PKCdelta and FAK activation through an integrin/FAK-positive feedback loop, in correlation with a reduced FAK time residency at focal adhesions. Notably, a K8/K18 loss results to a time course modulation of the receptor of activated C-kinase-1, beta1-integrin, plectin, PKC, and c-Src complex formation. Although the K8/K18 modulation of hepatocyte adhesion also occurs through a PKC mediation, these differentiated epithelial cells exhibit minimal migrating ability, in link with marked differences in protein partner content and distribution. Together, these results uncover a key regulatory function for K8/K18 IFs in the PKC-mediated integrin/FAK-dependent adhesion and migration of simple epithelial cells. PMID- 20357008 TI - Different effects of sevoflurane, desflurane, and isoflurane on early and late left ventricular diastolic function in young healthy adults. AB - BACKGROUND: Knowledge on the effects of volatile anaesthetics on left ventricular (LV) diastolic function in humans in vivo is limited. We tested the hypothesis that sevoflurane, desflurane, and isoflurane do not impair LV diastolic function in young healthy humans. METHODS: Sixty otherwise healthy subjects (aged 18-48 yr) undergoing minor procedures under general anaesthesia were studied. After randomization for the anaesthetic, transthoracic echocardiographic examinations were performed at baseline and under anaesthesia with 1 minimum alveolar concentration (MAC) of the volatile anaesthetics during spontaneous breathing and intermittent positive pressure ventilation (IPPV). Peak early (E') and late (A') diastolic velocities of the mitral annulus were studied as the main echocardiographic indicators of diastolic function. RESULTS: During anaesthesia with 1 MAC under spontaneous breathing, E' increased with desflurane (P<0.001), was not significantly different with isoflurane (P=0.030), and decreased with sevoflurane (P=0.006). During IPPV, E' was similar to baseline with desflurane (P=0.550), insignificantly decreased with isoflurane (P=0.029), and decreased with the sevoflurane group (P<0.001). In contrast, A' was similarly reduced in all groups during spontaneous breathing without further changes during IPPV. Haemodynamic changes were comparable in all study groups. CONCLUSIONS: The findings of this in vivo study indicate that desflurane and isoflurane, and most likely sevoflurane, have no relevant direct negative effect on early diastolic relaxation in young healthy humans. In contrast, all three volatile anaesthetics appear to impair late diastolic LV filling during atrial contraction. PMID- 20357009 TI - Surgical resection for oral tongue cancer pulmonary metastases. AB - The aim of this study was to evaluate the efficacy of surgical resection of oral tongue cancer (OTC) pulmonary metastases. Between 1977 and 2003, 23 OTC patients who developed 1-3 pulmonary metastases underwent metastasectomy. There were 14 men and nine women with a median age at the time of first metastasectomy of 56 years. All patients had advanced squamous cell OTC with synchronous or metachronous regional lymph node metastases. The median tumor-free interval after the last OTC treatment was 12 months. Five patients underwent pneumonectomy, three bilobectomy, 13 lobectomy, and two wedge resection. Two patients underwent a second pulmonary metastasectomy. One patient continues to survive, without recurrence 19 years after metastasectomy. Another patient was alive with disease at 24 months after metastasectomy but was lost to follow-up. Twenty-two out of 23 patients developed systemic metastases. The median interval to systemic recurrence after lung resection was 4.1 months, and 21 out of 23 patients died of OTC (median, 9.5 months) after metastasectomy. Most patients who underwent pulmonary metastasectomy died of the disease within two years of metastasectomy. Even for patients with a solitary metastasis, surgical metastasectomy is not a recommended treatment option. PMID- 20357010 TI - Spontaneous combined lung and bowel hernia following an episode of acute bronchitis. AB - Spontaneous lung hernias are unusual conditions which usually follow attacks of excessive straining. Spontaneous bowel hernias are even rarer. Here, we present the first reported case of a combined spontaneous herniation of both the lung and bowel following an attack of acute bronchitis and coughing together with a description of surgical approach and repair. PMID- 20357011 TI - Aortic root distensibility and cross-sectional areas in stented and subcoronary stentless bioprostheses in pigs. AB - A flexible aortic root is essential for natural leaflet stress distribution. It is suggested that stentless bioprosthetic valves retain the flexibility of native valves. We investigated aortic root distensibility and cross-sectional area (CSA) in stentless (Solo, n=4; Toronto SPV, n=7), stented (Mitroflow, n=8) and in native valves (n=8) in pigs. Magnetic resonance imaging was performed to assess aortic root areas. At the annular level the Solo valve had a larger CSA (2.83+/ 0.26 cm(2)) than both the Mitroflow (2.24+/-0.23 cm(2)) and Toronto SPV (1.87+/ 0.59 cm(2)) (P=0.003; P=0.01). At the sino-tubular junction the Mitroflow valve had a significantly larger CSA (2.96+/-0.80 cm(2)) than the Toronto SPV (2.05+/ 0.47 cm(2); P=0.02). At the annular level the percentage change in area between end-diastole and end-systole was lower for the Mitroflow than for all the other valves (P=0.006). No difference was found between native and stentless valves. In conclusion, the Solo valve had a larger CSA at the annulus than both the Mitroflow and the Toronto SPV. However, the stentless valves had a smaller CSA at the sino-tubular junction than the Mitroflow. We, furthermore, found that implantation of stentless heart valves preserves aortic root distensibility at the annular level in pigs. PMID- 20357012 TI - Medium to long-term clinical outcome following stentless aortic valve replacement: comparison between allograft and xenograft valves. AB - The xenograft stentless valve was designed to emulate the haemodynamic performance of the allograft. Early outcomes using either surgical option (stentless xenograft valve or allograft) have been similar. However, follow-up outcomes remain to be compared. Between 1st January 1991 and 1st January 2001, 415 patients underwent aortic valve replacement. Two hundred and seventeen patients received an allograft and in 198 patients a Toronto stentless porcine valve (TSPV) was implanted. Mean time to follow-up was 6.3+/-4.4 years. Ten years freedom from structural valve deterioration (SVD) (TSPV 86+/-5%, allograft 82+/ 5%, P=0.49) and freedom from reoperation (RE) (TSPV 80+/-4% vs. allograft 85+/ 4%, P=0.61) were not significantly different. The TSPV was associated with significantly worse actuarial survival than the homograft (TSPV 40+/-4% vs. homograft 55+/-4%, P=0.02). However, after adjustment for other variables using a multivariate model, TSPV use was not an independent predictor of impaired late survival (LS) (P=0.44). Kaplan-Meier analysis in a subgroup of patients aged 45 65 years comparing LS, RE and SVD between xenografts and allografts identified similar results. The porcine stentless valve may be associated with similar clinical performance to the allograft over the medium to long-term. PMID- 20357013 TI - Cardiac herniation and lung torsion following heart and lung transplantation. AB - A 45-year-old male heart-lung transplant recipient reported reduced exercise tolerance two months post-transplant. Spirometry, right heart pressures, bronchoscopy, trans-bronchial and endomyocardial biopsy were normal. Investigations demonstrated posterior and leftwards herniation of the heart through the posterior pericardial window created during the transplant operation with secondary 90 degrees forward twist of the left lung. This phenomenon generated mild functional narrowing of the left pulmonary artery demonstrable on magnetic resonance imaging. Cardiac herniation with lung torsion is a rare finding post heart-lung transplantation and usually manifests in the early postoperative period with haemodynamic compromise, requiring immediate correction. Our case demonstrates that heart graft herniation and secondary partial lung torsion can occur in the chronic phase without catastrophic consequences. PMID- 20357014 TI - Right mini-thoracotomy for left maze with transesophageal echo guidance. AB - Minimally invasive surgery (MIS) is widening with the development of new specialized instrumentation, allied with improved surgical experience and techniques, some of which have shown to be effective for the ablation of atrial fibrillation (AF). These developments enable us to achieve a so-called 'ideal procedure', epicardially on beating hearts, with less operative risk, high cure rates and rapid patient recovery. Epicor (St Jude Medical, Sunnyvale, CA, USA) low profile (LP) system is a device using high intensity focused ultrasound (HIFU). We describe the use of this technology for ablation of AF through MIS approach using transesophageal echocardiography (TEE) to pilot the ablation on mitral isthmus. Ten patients underwent monolateral small thoracotomy, through the 4th intercostal space. HIFU was carried out in all cases to create an epicardial box lesion of the pulmonary veins (PVs) and mitral isthmus. TEE was employed to guide the positioning of the ablation device on mitral isthmus, in all patients. There were no mortalities or major complications, including pacemaker implantation. One patient had postoperative atrial tachycardia and was cardioverted before hospital discharge. Three patients had a postoperative AF and were scheduled for cardioversion after three months, and one patient spontaneously revealed a normal sinus rhythm (SR). During the follow-up period, all patients recorded a normal SR. We consider Epicor LP system safe and effective for AF ablation through a single right minimal invasive approach. PMID- 20357015 TI - CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor. AB - Chloride intracellular channel 5 (CLIC5) and other CLIC isoforms have been implicated in a number of biological processes, but their specific functions are poorly understood. The association of CLIC5 with ezrin and the actin cytoskeleton led us to test its possible involvement in gastric acid secretion. Clic5 mutant mice exhibited only a minor reduction in acid secretion, Clic5 mRNA was expressed at only low levels in stomach, and Clic5 mutant parietal cells were ultrastructurally normal, negating the hypothesis that CLIC5 plays a major role in acid secretion. However, the mutants exhibited gastric hemorrhaging in response to fasting, reduced monocytes and granulocytes suggestive of immune dysfunction, behavioral and social disorders suggestive of neurological dysfunction, and evidence of a previously unidentified metabolic defect. Wild type and mutant mice were maintained on normal and high-fat diets; plasma levels of various hormones, glucose, and lipids were determined; and body composition was studied by quantitative magnetic resonance imaging. Clic5 mutants were lean, hyperphagic, and highly resistant to diet-induced obesity. Plasma insulin and glucose levels were reduced, and leptin levels were very low; however, plasma triglycerides, cholesterol, phospholipids, and fatty acids were normal. Indirect calorimetry revealed increased peripheral metabolism and greater reliance on carbohydrate metabolism. Because Clic5 mutants were unable to maintain energy reserves, they also exhibited increased susceptibility to fasting-induced torpor, as indicated by telemetric measurements showing episodes of reduced body temperature and heart rate. These data reveal a requirement for CLIC5 in the maintenance of normal systemic energy metabolism. PMID- 20357016 TI - The role of amylin in the control of energy homeostasis. AB - Amylin is an important player in the control of nutrient fluxes. Amylin reduces eating via a meal size effect by promoting meal-ending satiation. This effect seems to depend on a direct action in the area postrema (AP), which is an area rich in amylin receptors. Subsequent to the activation of AP neurons, the neural signal is conveyed to the forebrain via relays involving the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (lPBN) to the lateral hypothalamic area (LHA) and other hypothalamic nuclei. While the NTS and lPBN seem to be necessary for amylin's eating inhibitory effect, the role of the LHA has not yet been fully investigated. Amylin may also act as an adiposity signal. Plasma levels of amylin are higher in obese individuals, and chronic infusion of amylin into the brain reduces body weight gain and adiposity; chronic infusion of an amylin receptor antagonist into the brain increases body adiposity. Amylin increases energy expenditure in rats; this effect occurs under various experimental conditions after peripheral and central administration. Together, these animal data, but also clinical data in humans, indicate that amylin is a promising candidate for the treatment of obesity; effects are most pronounced when amylin is combined with leptin. Finally, recent findings indicate that amylin acts as a neurotrophic factor in specific brain stem areas. Whether this effect may be relevant under physiological conditions requires further studies. PMID- 20357017 TI - Counterpoint: physiologists should not distinguish "sex" and "gender". PMID- 20357018 TI - Point: a call for proper usage of "gender" and "sex" in biomedical publications. PMID- 20357019 TI - Sustained hypercapnia induces cerebral microvascular degeneration in the immature brain through induction of nitrative stress. AB - Hypercapnia is regularly observed in chronic lung disease, such as bronchopulmonary dysplasia in preterm infants. Hypercapnia results in increased nitric oxide synthase activity and in vitro formation of nitrates. Neural vasculature of the immature subject is particularly sensitive to nitrative stress. We investigated whether exposure to clinically relevant sustained high CO(2) causes microvascular degeneration in the newborn brain by inducing nitrative stress, and whether this microvascular degeneration has an impact on brain growth. Newborn rat pups were exposed to 10% CO(2) as inspired gas (Pa(CO(2)) = 60-70 mmHg) starting within 24 h of birth until postnatal day 7 (P7). Brains were notably collected at different time points to measure vascular density, determine brain cortical nitrite/nitrate, and trans-arachidonic acids (TAAs; products of nitration) levels as effectors of vessel damage. Chronic exposure of rat pups to high CO(2) (Pa(CO(2)) approximately 65 mmHg) induced a 20% loss in cerebrovascular density at P3 and a 15% decrease in brain mass at P7; at P30, brain mass remained lower in CO(2)-exposed animals. Within 24 h of exposure to CO(2), brain eNOS expression and production of nitrite/nitrate doubled, lipid nitration products (TAAs) increased, and protein nitration (3 nitrotyrosine immunoreactivity) was also coincidently augmented on brain microvessels (lectin positive). Intracerebroventricular injection of TAAs (10 microM) replicated cerebrovascular degeneration. Treatment of rat pups with NOS inhibitor (L-N(omega)-nitroarginine methyl ester) or a peroxynitrite decomposition catalyst (FeTPPS) prevented hypercapnia-induced microvascular degeneration and preserved brain mass. Cytotoxic effects of high CO(2) were reproduced in vitro/ex vivo on cultured endothelial cells and sprouting microvessels. In summary, hypercapnia at values frequently observed in preterm infants with chronic lung disease results in increased nitrative stress, which leads to cerebral cortical microvascular degeneration and curtails brain growth. PMID- 20357020 TI - Variation in levels of luteinizing hormone and reproductive photoresponsiveness in a population of white-footed mice (Peromyscus leucopus). AB - Natural genetic variation in reproduction and life history strategies is a manifestation of variation in underlying regulatory neuronal and endocrine systems. A test of the hypothesis that genetic variation in luteinizing hormone (LH) level could be related to a life history trait, seasonal reproduction, was conducted on artificial selection lines from a wild-source population of white footed mice (Peromyscus leucopus). Variation exists in the degree of suppression of reproduction by winter short-day photoperiods (SD) in wild-source individuals and in the laboratory population. In this population, most individuals from a photoperiod-responsive (R) artificial selection line are strongly suppressed reproductively in SD, while most individuals from a photoperiod-nonresponsive (NR) artificial selection line are only weakly reproductively suppressed in SD. We assayed levels of LH to test for genetic variation between lines that could contribute to variation in reproductive status in SD. Females from both lines were raised in long-day photoperiods (LD) or SD, ovariectomized under isoflurane anesthesia, and given estradiol implants. Levels of LH were significantly higher in the NR line than in the R line, indicating genetic variation for levels of LH. Levels of LH were higher in LD than in SD, indicating that levels of LH were sensitive to photoperiod treatment even with a controlled level of estradiol negative feedback. The results indicate that there is genetic variation in levels of LH that could be functionally important both in the laboratory in SD and in the wild population in winter. Thus genetic variation in levels of LH is a plausible causal factor determining winter reproductive phenotype in the wild population. PMID- 20357022 TI - Gut glucose metabolism in rainbow trout: implications in glucose homeostasis and glucosensing capacity. AB - The main objective of the present study was to evaluate the relative contribution of the intestine to glucose homeostasis in rainbow trout. In a first set of in vivo experiments trout were subjected to oral glucose treatments alone or in combination with insulin injections to assess changes in glucose-related enzymes activities, metabolite levels, and mRNA levels. Rainbow trout gut displays an important glucose metabolism that includes the ability to store glucose as glycogen (mostly in the muscle layers) and a large capacity to oxidize glucose. This constitutes a surprising result for a carnivorous fish. In a second set of in vivo experiments, trout received an oral amino acid solution alone or in combination with insulin injection to determine whether other factors besides fasting could regulate gluconeogenesis in intestine. The results confirm the absence of regulation of gluconeogenesis in trout gut, which does not respond to hormones, glucose, lactate, or amino acid changes, either in vivo or in vitro. We also fully characterized gut glucose metabolism in vitro. We observed that a large amount of glucose is oxidized to lactate, supporting the importance of glucose in gut metabolism. Moreover, we corroborated the minor actions of insulin in trout gut, whereas other hormones such as glucagon-like peptide-1 and C peptide appear to be major hormonal regulators of glucose metabolism in fish gut. Finally, we obtained the first evidence for the existence of a glucosensing mechanism in the midgut of this carnivorous species. PMID- 20357023 TI - Adaptive trends in respiratory control: a comparative perspective. AB - In 1941, August Krogh published a monograph entitled The Comparative Physiology of Respiratory Mechanisms (Philadelphia, PA: University of Pennsylvania Press, 1941). Since that time comparative studies have continued to contribute significantly to our understanding of the fundamentals of respiratory physiology and the adaptive trends in these processes that support a broad range of metabolic performance under demanding environmental conditions. This review specifically focuses on recent advances in our understanding of adaptive trends in respiratory control. Respiratory rhythm generators most likely arose from, and must remain integrated with, rhythm generators for chewing, suckling, and swallowing. Within the central nervous system there are multiple "segmental" rhythm generators, and through evolution there is a caudal shift in the predominant respiratory rhythm-generating site. All sites, however, may still be capable of producing or modulating respiratory rhythm under appropriate conditions. Expression of the respiratory rhythm is conditional on (tonic) input. Once the rhythm is expressed, it is often episodic as the basic medullary rhythm is turned on/off subject to a hierarchy of controls. Breathing patterns reflect differences in pulmonary mechanics resulting from differences in body wall and lung architecture and are modulated in different species by various combinations of upper and lower airway mechanoreceptors and arterial chemoreceptors to protect airways, reduce dead space ventilation, enhance gas exchange efficiency, and reduce the cost of breathing. PMID- 20357021 TI - Physical (in)activity-dependent alterations at the rostral ventrolateral medulla: influence on sympathetic nervous system regulation. AB - A sedentary lifestyle is a major risk factor for cardiovascular disease, and rates of inactivity and cardiovascular disease are highly prevalent in our society. Cardiovascular disease is often associated with overactivity of the sympathetic nervous system, which has both direct and indirect effects on multiple organ systems. Although it has been known for some time that exercise positively affects the brain in terms of memory and cognition, only recently have changes in how the brain regulates the cardiovascular system been examined in terms of physical activity and inactivity. This brief review will discuss the evidence for physical activity-dependent neuroplasticity related to control of sympathetic outflow. It will focus particularly on recent studies from our laboratory and others that have examined changes that occur in the rostral ventrolateral medulla (RVLM), considered one of the primary brain regions involved in the regulation and generation of sympathetic nervous system activity. PMID- 20357024 TI - Diversified cardiovascular actions of six homologous natriuretic peptides (ANP, BNP, VNP, CNP1, CNP3, and CNP4) in conscious eels. AB - The natriuretic peptide (NP) family consists of seven paralogs [atrial NP (ANP), brain NP (BNP), ventricular NP (VNP), and C-type NP 1-4 (CNP1-4)] in teleosts, but relative biological activity of the seven NPs has not been comprehensively examined using homologous peptides. In this study, we newly identified CNP3 and CNP4 in eels to use homologous peptides, but the CNP2 gene may have been silenced in this species. The CNP4 gene was expressed exclusively in the brain as CNP1, but the CNP3 gene, from which cardiac ANP, BNP, and VNP were generated by tandem duplication, was most abundantly expressed in the pituitary, suggesting its local action. All NPs induced hypotension dose dependently after intra-arterial injection with a potency order of ANP > VNP > BNP > CNP4 > CNP1 = CNP3. The degree of hypotension was similar at the ventral and dorsal aorta, indicating similar actions on the branchial and systemic circulation. The hypotension induced by cardiac NPs was longer lasting than CNPs, probably because of the difference in preferential receptors. Among cardiac NPs, the hypotensive effect of VNP lasted much longer than those of ANP and BNP, even though VNP disappeared from the blood more quickly than ANP. To analyze the unique effect of VNP, we examined possible involvement of the autonomic nervous system using ANP, VNP, and CNP3. Beta-adrenergic blockade diminished hypotensive effects of all three NPs, but alpha-adrenergic and cholinergic blockade enhanced only the effect of VNP, suggesting a specific mechanism for the VNP action. The NP-induced tachycardia was diminished by all blockers examined. Furthermore, the cardiovascular action of VNP was not impaired by a blocker of NP receptor, HS-142-1. Taken together, the homologous NPs exhibit diverse cardiovascular actions in eels partially through the autonomic nervous system, and the unique VNP action may be mediated by a novel receptor that has not been identified in teleosts. PMID- 20357025 TI - Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation. AB - Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications. PMID- 20357026 TI - Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats. AB - The cellular effects of gastric electrical stimulation (GES), which has recently been introduced as a potential therapy for the treatment of gastroparesis and obesity, were investigated in rat antrum smooth muscle cells (SMCs). Effects on cell membrane potentials of single electrical current pulses (pulse width from 0.1 ms to 200 ms) and 2-s pulse train stimuli with different pulse widths (0.1-4 ms), different frequencies (20-200 Hz), and different intensities were studied: 1) the stimulus amplitude had an exponential relationship to the pulse width from 2 ms to 200 ms, along with a rapidly rising strength-duration curve at pulse widths less than 5 ms, and a relatively flat curve at pulse widths greater than 50 ms; 2) when the pulse frequency was at 80 Hz or above, pulse train electrical stimulation, with a pulse width of 2 ms or above but not < or = 1 ms, was able to depolarize cell membrane potentials to above -30 mV and/or generate action potentials. Electrical stimulation with a single long pulse and a width of 50 ms or greater is effective in depolarizing cell membrane potentials of SMCs with low amplitude. Pulse train electrical stimulation with a pulse width of < or = 1 ms fails to generate action potentials in SMCs, whereas pulse train electrical stimulation with a pulse width of 2-4 ms and a sufficiently high pulse frequency is able to generate action potentials. These cellular findings may be useful in optimizing stimulation parameters of GES. PMID- 20357028 TI - Acute neurosteroids inhibit the spinal reflex potentiation via GABAergic neurotransmission. AB - Recently, we demonstrated a chronic neurosteroid-dependent inhibition of activity dependent spinal reflex potentiation (SRP), but it remains unclear whether neurosteroids acutely modulate SRP induction. This study shows progesterone as well as two of its 3alpha,5alpha-derivatives, allopregnalonone and 3alpha,5alpha tetrahydrodeoxycorticosterone (THDOC), to be capable of producing acute GABA(A) receptor (GABA(A)R)-dependent inhibition of SRP. When compared with test simulation (1 stimulation/30 s) of pelvic afferent nerves that evoked a baseline reflex activity in an external urethra sphincter electromyogram, repetitive stimulation (RS; 1 stimulation/1 s) induced SRP characterized by an increase in the evoked activity. Intrathecal progesterone (3-30 muM, 10 microl) at 10 min before stimulation onset dose dependently prevented RS induction. Intrathecal allopregnalonone (10 muM, 10 microl it) and THDOC (10 microM, 10 microl it) also prevented the SRP caused by RS. Pretreatment with the GABA(A)R antagonist bicuculline (10 microM, 10 microl it) at 1 min before progesterone/neurosteroid injection attenuated the inhibition of SRP caused by progesterone, allopregnanolone, and THDOC. Results suggest that progesterone and its neurosteroid metabolites may be crucial to the development of pelvic visceral neuropathic/postinflammatory pain and imply clinical use of neurosteroids, such as allopregnanolone and THDOC, for visceral pain treatment. PMID- 20357027 TI - Cerebrovascular responses in mice deficient in the potassium channel, TREK-1. AB - We tested the hypothesis that TREK-1, a two-pore domain K channel, is involved with dilations in arteries. Because there are no selective activators or inhibitors of TREK-1, we generated a mouse line deficient in TREK-1. Endothelium mediated dilations were not different in arteries from wild-type (WT) and TREK-1 knockout (KO) mice. This includes dilations of the middle cerebral artery to ATP, dilations of the basilar artery to ACh, and relaxations of the aorta to carbachol, a cholinergic agonist. The nitric oxide (NO) and endothelium-dependent hyperpolarizing factor components of ATP dilations were identical in the middle cerebral arteries of WT and TREK-1 KO mice. Furthermore, the NO and cyclooxygenase-dependent components were identical in the basilar arteries of the different genotypes. Dilations of the basilar artery to alpha-linolenic acid, an activator of TREK-1, were not affected by the absence of TREK-1. Whole cell currents recorded using patch-clamp techniques were similar in cerebrovascular smooth muscle cells (CVSMCs) from WT and TREK-1 KO mice. alpha-linolenic acid or arachidonic acid increased whole cell currents in CVSMCs from both WT and TREK-1 KO mice. The selective blockers of large-conductance Ca-activated K channels, penitrem A and iberiotoxin, blocked the increased currents elicited by either alpha-linolenic or arachidonic acid. In summary, dilations were similar in arteries from WT and TREK-1 KO mice. There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1. PMID- 20357029 TI - Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice. AB - In the present study, we evaluated the roles of type II and type III sodium dependent P(i) cotransporters in fibroblast growth factor 23 (FGF23) activity by administering a vector encoding FGF23 with the R179Q mutation (FGF23M) to wild type (WT) mice, Npt2a knockout (KO) mice, Npt2c KO mice, and Npt2a(-/-)Npt2c(-/-) mice (DKO mice). In Npt2a KO mice, FGF23M induced severe hypophosphatemia and markedly decreased the levels of Npt2c, type III Na-dependent P(i) transporter (PiT2) protein, and renal Na/P(i) transport activity. In contrast, in Npt2c KO mice, FGF23M decreased plasma phosphate levels comparable to those in FGF23M injected WT mice. In DKO mice with severe hypophosphatemia, FGF23M administration did not induce an additional increase in urinary phosphate excretion. FGF23 administration significantly decreased intestinal Npt2b protein levels in WT mice but had no effect in Npt2a, Npt2c, and DKO mice, despite marked suppression of plasma 1,25(OH)(2)D(3) levels in all the mutant mice. The main findings were as follow: 1) FGF23-dependent phosphaturic activity in Npt2a KO mice is dependent on renal Npt2c and PiT-2 protein; 2) in DKO mice, renal P(i) reabsorption is not further decreased by FGF23M, but renal vitamin D synthesis is suppressed; and 3) downregulation of intestinal Npt2b may be mediated by a factor(s) other than 1,25(OH)(2)D(3). These findings suggest that Npt2a, Npt2c, and PiT-2 are necessary for the phosphaturic activity of FGF23. Thus complementary regulation of Npt2 family proteins may be involved in systemic P(i) homeostasis. PMID- 20357030 TI - Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease. AB - Angiotensin-converting enzyme 2 (ACE2) is expressed at high levels in the kidney and converts angiotensin II (ANG II) to ANG-(1-7). We studied the effects of ACE2 inhibition and ANG-(1-7) in the (5/6) nephrectomy ((5/6) Nx) mouse model of chronic kidney disease (CKD). Male FVB mice underwent sham surgery (Sham) or (5/6) Nx and were administered either vehicle, the ACE2 inhibitor MLN-4760 (MLN), the AT(1) receptor antagonist losartan, MLN plus losartan, or ANG-(1-7) for 4 wk. In (5/6) Nx mice with or without MLN, kidney cortical ACE2 protein expression was significantly decreased at 4 wk, compared with Sham. Inhibition of ACE2 caused a decrease in renal cortical ACE2 activity. Kidney cortical ACE expression and activity did not differ between groups of mice. In (5/6) Nx mice treated with MLN, kidney levels of ANG II were significantly increased, compared with Sham. (5/6) Nx induced a mild but insignificant increase in blood pressure (BP), a 50% reduction in FITC-inulin clearance, and a significant increase in urinary albumin excretion. ACE2 inhibition in (5/6) Nx mice did not affect BP or FITC-inulin clearance but significantly increased albuminuria compared with (5/6) Nx alone, an effect reversed by losartan. Treatment of (5/6) Nx mice with ANG-(1-7) increased kidney and plasma levels of ANG-(1-7) but did not alter BP, FITC-inulin clearance, or urinary albumin excretion, and it increased relative mesangial area. These data indicate that kidney ACE2 is downregulated in the early period after (5/6) Nx. Inhibition of ACE2 in (5/6) Nx mice increases albuminuria via an AT(1) receptor-dependent mechanism, independent of BP. In contrast, ANG-(1-7) does not affect albuminuria after (5/6) Nx. We propose that endogenous ACE2 is renoprotective in CKD. PMID- 20357031 TI - Decrease in dietary K intake stimulates the generation of superoxide anions in the kidney and inhibits K secretory channels in the CCD. AB - We previously demonstrated that K depletion inhibited ROMK-like small-conductance K channels (SK) in the cortical collecting duct (CCD) and that the effect was mediated by superoxide anions that stimulated Src family protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) (51). However, because animals on a K-deficient diet had a severe hypokalemia, superoxide-dependent signaling may not regulate ROMK channels under physiological conditions with a normal plasma K concentration. In the present study, we used the patch-clamp technique and Western blot to examine the effect of a moderate K restriction on ROMK-like SK channels and the role of PTK and MAPK in regulating apical K channels in the CCD of animals on a low-K diet (LK; 0.1% K). Rats and mice fed a LK diet for 7 days had a normal plasma K concentration. However, a LK intake increased the expression of angiotensin II type 1 receptor in the kidney. Moreover, patch-clamp experiments demonstrated that LK intake decreased the probability finding SK channels and channel activity defined by NP(o) (a product of channel number and open probability) in the CCD of both rat and mouse kidneys. Also, LK intake significantly stimulated the production of superoxide anions in the renal cortex and outer medulla in both rats and mice and increased superoxide level in the rat CCD. Moreover, LK intake augments the phosphorylation of p38 and ERK MAPK, the expression of c-Src and tyrosine phosphorylation of ROMK channels. However, treatment of animals with tempol abolished the effect of LK intake on MAPK and c Src and increased ROMK channel activity in comparing with those of nontreated rats on a LK diet. Inhibiting p38 and ERK with SB202190 and PD98059 significantly stimulated SK in the CCD in rats on a LK diet. In addition, inhibition of PTK with herbimycin A activated SK channels in the CCD from rats on a LK diet. We conclude that LK intake stimulates the generation of superoxide anion and related products and that MAPK and Src family PTK play a physiological role in inhibiting apical K channels in the principal cells in response to LK intake. PMID- 20357033 TI - Maintenance of physical activity and body weight in relation to subsequent quality of life in postmenopausal breast cancer patients. AB - BACKGROUND: We prospectively examined the association between physical activity, body weight and quality of life in Dutch postmenopausal early breast cancer patients treated with adjuvant endocrine therapy. PATIENTS AND METHODS: In this side study of a large clinical trial, lifestyle and quality-of-life questionnaires were filled out 1 and 2 years after the start of endocrine therapy (T1 and T2, respectively) and included a pre-diagnosis lifestyle assessment (T0). A total of 435 breast cancer patients returned both questionnaires. RESULTS: Individuals with a physical activity level above the median who maintained this level from T0 to T1 reported the best global quality of life and physical functioning and the least fatigue at T2, as compared with individuals with low levels of physical activity which further decreased after diagnosis (difference of +16, +14, and -22 points on a 0-100 quality-of-life scale, respectively; P < 0.01). Overweight or obese women who gained body weight after diagnosis reported worst quality of life and most fatigue as compared with women who maintained a stable body weight (difference of -8, -10 and +2 points, respectively; P < 0.01). CONCLUSION: Maintaining high pre-diagnosis physical activity levels and a healthy body weight is associated with better quality of life after breast cancer. PMID- 20357034 TI - Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary. AB - BACKGROUND: Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer. We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin (PLD) in patients with advanced taxane-pretreated ovarian and breast cancer. METHODS: Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients. RESULTS: Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination. The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2) on days 1, 8, and 15 plus PLD 30 mg/m(2) given on day 1, repeated every 4 weeks. Hand-foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks. Objective responses were observed in 3 of 13 patients (23%) with breast cancer and 5 of 17 patients (29%) with ovarian cancer. CONCLUSION: Ixabepilone may be safely combined with PLD, but tolerability is highly dependent upon the scheduling of both agents. This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these settings. PMID- 20357035 TI - Human immunodeficiency virus postexposure prophylaxis at IBadan, Nigeria. AB - HIV infection from occupational and nonoccupational exposures can be prevented through risk assessment and management with antiretroviral drug therapy (ART). This study sought to examine the pattern of presentation and outcome of clients who were given postexposure prophylaxis (PEP) at the University College Hospital, Ibadan, Nigeria. A retrospective review of case notes of clients presenting for HIV PEP from January 2005 to December 2006 was carried out. A total of 48 clients with a mean age of 27.9 +/- 12.3 years underwent PEP during the period under review. Rape constituted 50% of reasons for PEP, while needle pricks and blood splash into mucous membranes constituted 25% each. Among those who received therapy, 10 (23.8%) could not complete drug therapy because of side effects. Although no client was HIV positive after the recommended 6 months of follow-up, 8 (16.7%) clients did not complete attendance to the clinic during the period. PMID- 20357036 TI - HCV recurrence in HIV-infected patients after liver transplant. AB - Patients coinfected with hepatitis C virus (HCV) and HIV undergoing liver transplantation (LT) are at risk of early, aggressive HCV recurrence. This study investigates the use of frequent protocol-driven biopsies to identify HCV recurrence post LT in coinfected patients. Five consecutive HIV/HCV-coinfected patients underwent LT. Liver biopsies were obtained post LT at 1 hour; days 7, 120, and 365; then annually; and as clinically indicated. Stage 2 (Ishak) or higher fibrosis occurred in 4 of the 5 patients by 60, 120, 270, and 365 days. Two patients died of HCV recurrence and liver failure at 6 and 35 months post LT. Three patients survived more than 4 years after LT, 2 having sustained virologic responses to anti-HCV treatment. Another has histologic recurrence not responding to treatment. Hepatitis C virus recurrence can be rapid and aggressive after LT in HIV-coinfected patients. Serial biopsies identify recurrence early, allowing for prompt initiation of treatment. PMID- 20357037 TI - Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells. AB - Hepatitis C virus (HCV) core protein genotype 3a induces the expression of suppressor of cytokine signalling protein 7 (SOCS-7), which is partially involved in the development of insulin resistance. The aim of the present study was to investigate the mechanism through which the core protein regulates SOCS-7 expression. We have explored, in the in vitro model of Huh-7 cells expressing the HCV core protein of genotype 3a, whether the expression of SOCS-7 as well as of other members of the SOCS family (SOCS-1 and SOCS-3) was activated by the STAT3 pathway, using immunoblotting and real-time PCR upon alpha interferon (IFN-alpha) treatment. We found that, whilst IFN-alpha treatment induced STAT3 activation and consequently SOCS-1 and SOCS-3 upregulation in HCV genotype 3a core-expressing Huh-7 cells, SOCS-7 mRNA expression was independent of STAT3 and seemed to be modulated by peroxisome proliferator-activated receptor gamma (PPAR-gamma) activity, as demonstrated by quantitative real-time PCR and immunoblot detection after treatment with the PPAR-gamma agonist rosiglitazone or the PPAR-gamma antagonist GW9262. In contrast to the other studied members of the SOCS family (1 and 3), which are regulated by STAT3 activation, SOCS-7 expression appears to be STAT3-independent and seems to be regulated instead by PPAR-gamma. This is the first report proposing a molecular mechanism through which the HCV core protein (genotype 3a) modulates SOCS-7 expression. PMID- 20357032 TI - Impact of setting of care on pain management in patients with cancer: a multicentre cross-sectional study. AB - BACKGROUND: No study has so far addressed whether differences do exist in the management of cancer-related pain in patients admitted to oncology and non oncology settings. PATIENTS AND METHODS: A multicentre cross-sectional study in 48 Italian hospitals has enrolled 819 patients receiving analgesic therapy for cancer-related pain. Demographics and clinical and analgesic therapy information have been prospectively collected by standardized forms. Adequacy of pain management has been evaluated by the Pain Management Index (PMI). RESULTS: Differences in the analgesic drug administration according to settings of care have been evident, non-opioids more frequently being administered in non-oncology units (19.6% versus 7.0%; P < 0.0001), while strong opioids are more frequently used in the oncology units (69.5% versus 51.9%; P < 0.0001). The number of patients receiving inadequate therapy (PMI < 0) has lowered in oncology compared with non-oncology units (11.3% versus 18.8%; P = 0.0024). Results of multiple logistic regression analysis have shown that the admission to non-oncology setting [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.15-2.67; P = 0.0096] and the absence of metastatic disease (OR = 1.60, 95% CI = 1.04-2.44; P = 0.0317) were independent factors associated with an increased risk of receiving an inadequate analgesic therapy. CONCLUSION: Oncology wards provide the most adequate standard of analgesic therapy for cancer-related pain. PMID- 20357038 TI - A novel method for preclinical detection of PrPSc in blood. AB - In this study, we demonstrate that a moderate amount of protein misfolding cyclic amplification (PMCA) coupled to a novel surround optical fibre immunoassay (SOFIA) detection scheme can be used to detect the disease-associated form of the prion protein (PrP(Sc)) in protease-untreated plasma from preclinical and clinical scrapie sheep, and white-tailed deer with chronic wasting disease, following natural and experimental infection. PrP(Sc), resulting from a conformational change of the normal (cellular) form of prion protein (PrP(C)), is considered central to neuropathogenesis and serves as the only reliable molecular marker for prion disease diagnosis. While the highest levels of PrP(Sc) are present in the central nervous system, the development of a reasonable diagnostic assay requires the use of body fluids that characteristically contain exceedingly low levels of PrP(Sc). PrP(Sc) has been detected in the blood of sick animals by means of PMCA technology. However, repeated cycling over several days, which is necessary for PMCA of blood material, has been reported to result in decreased specificity (false positives). To generate an assay for PrP(Sc) in blood that is both highly sensitive and specific, we have utilized limited serial PMCA (sPMCA) with SOFIA. We did not find any enhancement of sPMCA with the addition of polyadenylic acid nor was it necessary to match the genotypes of the PrP(C) and PrP(Sc) sources for efficient amplification. PMID- 20357039 TI - High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state. AB - Because of their high susceptibility to infection with various influenza virus strains, Madin-Darby canine kidney (MDCK) cells have been widely used as a substrate for influenza virus isolation and vaccine production. However, MDCK cells are also interferon (IFN) competent, and the type I IFN response is commonly thought to be a factor strongly inhibiting virus replication. Therefore, the inhibition of influenza virus replication by IFN signalling was analysed for an adherent MDCK cell line used in vaccine manufacturing. Depending on the respective virus strain, different levels of IFN induction and a corresponding upregulation of the IFN-induced myxovirus resistance protein 1 (Mx1) were observed. Suppression of IFN induction by transient expression of the viral non structural protein 1 protein enhanced replication of an influenza virus lacking NS1, but not wild-type strains. In agreement with this, stimulation of cells with MDCK cell-derived IFN prior to infection resulted only in a decrease in replication rate, and not in a change of final yields for wild-type influenza viruses. This lack of IFN-induced antiviral activity correlated with missing anti influenza activity of MDCK Mx proteins. No inhibitory effect on viral polymerase activity was found for canine Mx1 (cMx1) and cMx2 in minireplicon assays. In conclusion, in MDCK cells, IFN expression is not a limiting factor for influenza virus replication and this might partially be caused by a lack of anti-influenza activity of canine Mx proteins. PMID- 20357041 TI - Acute partial sleep deprivation increases food intake in healthy men. AB - BACKGROUND: Acute partial sleep deprivation increases plasma concentrations of ghrelin and decreases those of leptin. OBJECTIVE: The objective was to observe modifications in energy intake and physical activity after acute partial sleep deprivation in healthy men. DESIGN: Twelve men [age: 22 +/- 3 y; body mass index (in kg/m(2)): 22.30 +/- 1.83] completed a randomized 2-condition crossover study. During the first night of each 48-h session, subjects had either approximately 8 h (from midnight to 0800) or approximately 4 h (from 0200 to 0600) of sleep. All foods consumed subsequently (jam on buttered toast for breakfast, buffet for lunch, and a free menu for dinner) were eaten ad libitum. Physical activity was recorded by an actimeter. Feelings of hunger, perceived pleasantness of the foods, desire to eat some foods, and sensation of sleepiness were also evaluated. RESULTS: In comparison with the 8-h sleep session, subjects consumed 559 +/- 617 kcal (ie, 22%) more energy on the day after sleep restriction (P < 0.01), and preprandial hunger was higher before breakfast (P < 0.001) and dinner (P < 0.05). No change in the perceived pleasantness of the foods or in the desire to eat the foods was observed. Physical activity from 1215 to 2015 was higher after sleep restriction than after 8 h of sleep (P < 0.01), even though the sensation of sleepiness was more marked (P < 0.01). CONCLUSIONS: One night of reduced sleep subsequently increased food intake and, to a lesser extent, estimated physical activity-related energy expenditure in healthy men. These experimental results, if confirmed by long-term energy balance measurements, suggest that sleep restriction could be a factor that promotes obesity. This trial was registered at clinicaltrials.gov as NCT00986492. PMID- 20357040 TI - Serum n-6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP study. AB - BACKGROUND: The associations of serum omega-6 (n-6) fatty acids with lipoprotein subclasses at the population level are uncertain. OBJECTIVE: We aimed to examine associations between major n-6 fatty acids [ie, linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6)] and the lipoprotein subclasses VLDL, LDL, and HDL. DESIGN: We conducted a cross-sectional study in 1098 participants using population-based data from US white, Japanese American, Japanese, and Korean men aged 40-49 y. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Multiple linear regression models as a function of each fatty acid were used after adjustment for age, population, body mass index, pack years of smoking, alcohol consumption, diabetes, hypertension, and omega-3 (n-3) and trans fatty acids. RESULTS: Serum LA was inversely associated with large VLDL (beta = -0.62, P < 0.001), total LDL (beta = -22.08, P < 0.001), and small LDL (beta = -31.89, P < 0.001) particle concentrations and VLDL size (beta = -0.72, P < 0.001). Serum LA was positively associated with large HDL particle concentration (beta = 0.21, P < 0.001) and HDL size (beta = 0.03, P < 0.001). The patterns of association of AA with large VLDL and large HDL particle concentrations were comparable with those of LA. CONCLUSIONS: At the population level, higher serum concentrations of LA were significantly associated with lower concentrations of total LDL particles. Higher serum concentrations of LA and AA were significantly associated with a lower concentration of large VLDL particles and a higher concentration of large HDL particles. These associations were consistent across the population groups. This trial was registered at clinicaltrials.gov as NCT00069797. PMID- 20357042 TI - Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. AB - BACKGROUND: Folate deficiency has serious consequences for the fetus. Folic acid fortification of food addresses this problem. However, clinical consequences of vitamin B-12 deficiency may be worsened by high folic acid intakes, perhaps as a direct result of unmetabolized folic acid, which does not occur naturally in body tissues. OBJECTIVE: We attempted to attribute associations that we previously found between higher folate status and anemia and cognitive test performance to circulating unmetabolized folic acid or 5-methyltetrahydrofolate (5MeTHF). DESIGN: The subjects (n = 1858) were senior participants in the US National Health and Nutrition Examination Survey (1999-2002) who had normal renal function and reported no history of stroke, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries. Subjects had undergone a phlebotomy, a complete blood count, and cognitive and dietary assessments. RESULTS: Circulating unmetabolized folic acid was detected in approximately 33% of the subjects and was related to an increased odds of anemia in alcohol users. In seniors with a serum vitamin B-12 concentration <148 pmol/L or a plasma methylmalonic acid concentration > or =210 nmol/L, the presence compared with the absence of detectable circulating unmetabolized folic acid was related to lower cognitive test scores and lower mean cell volume. In the same subgroup, higher serum 5MeTHF was related to an increased odds of anemia and a marginally significantly decreased odds of macrocytosis. In seniors with a normal vitamin B-12 status, a higher serum 5MeTHF concentration was related to higher cognitive test scores. CONCLUSION: Results of this epidemiologic study were somewhat consistent with reports on the folic acid treatment of patients with pernicious anemia, but some findings were unexpected. PMID- 20357043 TI - Severe obesity, gestational weight gain, and adverse birth outcomes. AB - BACKGROUND: The 2009 Institute of Medicine (IOM) Committee to Reevaluate Gestational Weight Gain Guidelines concluded that there were too few data to inform weight-gain guidelines by obesity severity. Therefore, the committee recommended a single range, 5-9 kg at term, for all obese women. OBJECTIVE: We explored associations between gestational weight gain and small-for-gestational age (SGA) births, large-for-gestational-age (LGA) births, spontaneous preterm births (sPTBs), and medically indicated preterm births (iPTBs) among obese women who were stratified by severity of obesity. DESIGN: We studied a cohort of singleton, live-born infants without congenital anomalies born to obesity class 1 (prepregnancy body mass index [BMI (in kg/m(2))]: 30-34.9; n = 3254), class 2 (BMI: 35-39.9; n = 1451), and class 3 (BMI: > or =40; n = 845) mothers. We defined the adequacy of gestational weight gain as the ratio of observed weight gain to IOM-recommended gestational weight gain. RESULTS: The prevalence of excessive gestational weight gain declined, and weight loss increased, as obesity became more severe. Generally, weight loss was associated with an elevated risk of SGA, iPTB, and sPTB, and a high weight gain tended to increase the risk of LGA and iPTB. Weight gains associated with probabilities of SGA and LGA of < or =10% and a minimal risk of iPTB and sPTB were as follows: 9.1-13.5 kg (obesity class 1), 5.0-9 kg (obesity class 2), 2.2 to <5.0 kg (obesity class 3 white women), and <2.2 kg (obesity class 3 black women). CONCLUSION: These data suggest that the range of gestational weight gain to balance risks of SGA, LGA, sPTB, and iPTB may vary by severity of obesity. PMID- 20357044 TI - Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. AB - BACKGROUND: The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses, modulate nitric oxide synthesis, and promote vasodilation, which thereby improves blood flow. Resveratrol may therefore modulate aspects of brain function in humans. OBJECTIVE: The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults. DESIGN: In this randomized, double-blind, placebo-controlled, crossover study, 22 healthy adults received placebo and 2 doses (250 and 500 mg) of trans-resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min. Cerebral blood flow and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated hemoglobin, were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy. The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort (n = 9). RESULTS: Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, as indexed by total concentrations of hemoglobin. There was also an increase in deoxyhemoglobin after both doses of resveratrol, which suggested enhanced oxygen extraction, that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period. CONCLUSION: These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables. PMID- 20357045 TI - Suicide victim of paraquat poisoning make suitable corneal donor. AB - This report addresses the possibility of expanding transplant corneal donor pool by inclusion of more patients who have suffered poisoning with paraquat pre mortem. A 27-year-old depressed man committed suicide by ingesting 50 mL of 24% paraquat (Gramoxone, Syngenta, Taiwan). He was treated aggressively with gastric lavage, with large amounts of normal saline, followed by infusion of activated charcoal and magnesium citrate. Blood paraquat level was 1.90 MUg/mL. Charcoal hemoperfusion was performed for 8 hours using a charcoal-containing dialysis machine. Furthermore, pulse therapies of cyclophosphamide (15 mg/kg/day for 2 days) and methylprednisolone (1 g/day for 3 days) were administered, followed by dexamethasone (20 mg/day for 14 days). Methylprednisolone pulse therapy was repeated since PaO(2) on the 15th day of poisoning was <60 mm Hg. Chest radiography demonstrated diffuse ground glass opacities of both lungs, with thickening of the intralobular interstitium, compatible with interstitial pneumonitis. Arterial blood gas found persistent hypoxemia and large alveolar arterial oxygen tension differences. Respiratory failure developed on the 21st day and he was intubated for mechanical ventilatory support. As the patient expressed his wish for organ donation, the corneas were harvested after expiration on the 22nd day. His corneas were transplanted in two recipients and visual acuities of the recipients were doing well at 6 months after transplantation. PMID- 20357046 TI - Embryonic stem cells as models of trophoblast differentiation: progress, opportunities, and limitations. AB - While the determination of the trophoblast lineage and the facilitation of placental morphogenesis by trophoblast interactions with other cells of the placenta are crucial components for the establishment of pregnancy, these processes are not tractable at the time of human implantation. Embryonic stem cells (ESCs) provide an embryonic surrogate to derive insights into these processes. In this review, we will summarize current paradigms which promote trophoblast differentiation from ESCs, and potential opportunities for their use to further define signals directing morphogenesis of the placenta following implantation of the embryo into the endometrium. PMID- 20357047 TI - Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success. AB - Mammalian spermatozoa undergo a strong selection process along the female tract to guarantee fertilization by good quality cells, but risks of fertilization with DNA-damaged spermatozoa have been reported. In contrast, most external fertilizers such as fish seem to have weaker selection procedures. This fact, together with their high prolificacy and external embryo development, indicates that fish could be useful for the study of the effects of sperm DNA damage on embryo development. We cryopreserved sperm from rainbow trout using egg yolk and low-density lipoprotein as additives to promote different rates of DNA damage. DNA fragmentation and oxidization were analyzed using comet assay with and without digestion with restriction enzymes, and fertilization trials were performed. Some embryo batches were treated with 3-aminobenzamide (3AB) to inhibit DNA repair by the poly (ADP-ribose) polymerase, which is an enzyme of the base excision repair pathway. Results showed that all the spermatozoa cryopreserved with egg yolk carried more than 10% fragmented DNA, maintaining fertilization rates of 61.1+/-2.3 but a high rate of abortions, especially during gastrulation, and only 14.5+/-4.4 hatching success. Furthermore, after 3AB treatment, hatching dropped to 3.2+/-2.2, showing that at least 10% DNA fragmentation was repaired. We conclude that trout sperm maintains its ability to fertilize in spite of having DNA damage, but that embryo survival is affected. Damage is partially repaired by the oocyte during the first cleavage. Important advantages of using rainbow trout for the study of processes related to DNA damage and repair during development have been reported. PMID- 20357048 TI - Hypertension study in anaesthetized rabbits: protocol proposal for AT1 antagonists screening. AB - INTRODUCTION: The aim of this study was to establish an optimized fast and safe protocol for the pharmacological screening of AT(1) antagonists. MATERIALS AND METHODS: The pharmaceutical prototype AT(1) antagonist losartan, its active metabolite EXP3174 and the synthetic compound MMK1 were analysed in order to validate the protocol. Ang II was continuously infused while the animals received the drugs in two procedures. RESULTS: In the post-treatment procedure drugs were administered either in a single bolus dose or in a sequential manner. When losartan was administered in a single bolus dose, efficacy was evident until the 7th min (p=0.012) whilst EXP3174 infusion extended the efficiency up to the end of the study (p=0.006). In addition, the sequential injections of losartan prolonged the inhibitory time interval until the end of the study (p=0.045). In the pre-treatment procedure, results suggested a dose-dependent inhibitory effect for both antagonists. The pressor response to Ang II was unchanged after MMK1 administration either in the post- or in the pre-treatment mode. CONCLUSIONS: The proposed protocol appears to be safe, simple and fast for the pharmacological screening of AT(1) antagonists and enables the evaluation of new antagonists using lower doses than any other reported in the literature. PMID- 20357049 TI - Simultaneous administration of Ang(1-7) or A-779 does not affect the chronic hypertensive effects of angiotensin II in normal rats. AB - HYPOTHESIS: The following studies were designed to test the hypothesis that simultaneous administration of either Ang(1-7) or its antagonist A-779 would affect the chronic hypertensive effects of angiotensin II (Ang II). INTRODUCTION: Despite the well-described actions of Ang(1-7) and its role possessing opposite actions to Ang II, there have been few studies examining the role of Ang(1-7) in a chronic setting. It is well established that Ang(1-7) plays a protective role in preventing deleterious effects of Ang II in the heart, but little is known of its role in modulating the chronic hypertensive effects of Ang II. MATERIALS AND METHODS: Rats were instrumented with venous catheters and telemetric pressure transducers. Arterial pressure responses were measured in rats treated with Ang II (10 ng/kg/ min) (n=9) and compared with those treated with Ang II and Ang(1-7) (24 microg/kg/h) (n=8), or the Ang(1-7) antagonist A-779 (24 microg/kg/h) (n=7) for 8 days. RESULTS: Mean arterial pressure rose significantly and similarly in all three groups of rats, such that by day 8 of Ang II infusion, pressures had risen 25-30 mmHg in all rats. CONCLUSIONS: These results do not support the hypothesis that the chronic hypertensive effects of Ang II in normal rats are altered by co-administration of either Ang(1-7) or A-779. PMID- 20357050 TI - Copy number variation, chromosome rearrangement, and their association with recombination during avian evolution. AB - Chromosomal rearrangements and copy number variants (CNVs) play key roles in genome evolution and genetic disease; however, the molecular mechanisms underlying these types of structural genomic variation are not fully understood. The availability of complete genome sequences for two bird species, the chicken and the zebra finch, provides, for the first time, an ideal opportunity to analyze the relationship between structural genomic variation (chromosomal and CNV) and recombination on a genome-wide level. The aims of this study were therefore threefold: (1) to combine bioinformatics, physical mapping to produce comprehensive comparative maps of the genomes of chicken and zebra finch. In so doing, this allowed the identification of evolutionary chromosomal rearrangements distinguishing them. The previously reported interchromosomal conservation of synteny was confirmed, but a larger than expected number of intrachromosomal rearrangements were reported; (2) to hybridize zebra finch genomic DNA to a chicken tiling path microarray and identify CNVs in the zebra finch genome relative to chicken; 32 interspecific CNVs were identified; and (3) to test the hypothesis that there is an association between CNV, chromosomal rearrangements, and recombination by correlating data from (1) and (2) with recombination rate data from a high-resolution genetic linkage map of the zebra finch. We found a highly significant association of both chromosomal rearrangements and CNVs with elevated recombination rates. The results thus provide support for the notion of recombination-based processes playing a major role in avian genome evolution. PMID- 20357051 TI - Pronounced inter- and intrachromosomal variation in linkage disequilibrium across the zebra finch genome. AB - The extent of nonrandom association of alleles at two or more loci, termed linkage disequilibrium (LD), can reveal much about population demography, selection, and recombination rate, and is a key consideration when designing association mapping studies. Here, we describe a genome-wide analysis of LD in the zebra finch (Taeniopygia guttata) using 838 single nucleotide polymorphisms and present LD maps for all assembled chromosomes. We found that LD declined with physical distance approximately five times faster on the microchromosomes compared to macrochromosomes. The distribution of LD across individual macrochromosomes also varied in a distinct pattern. In the center of the macrochromosomes there were large blocks of markers, sometimes spanning tens of mega bases, in strong LD whereas on the ends of macrochromosomes LD declined more rapidly. Regions of high LD were not simply the result of suppressed recombination around the centromere and this pattern has not been observed previously in other taxa. We also found evidence that this pattern of LD has remained stable across many generations. The variability in LD between and within chromosomes has important implications for genome wide association studies in birds and for our understanding of the distribution of recombination events and the processes that govern them. PMID- 20357052 TI - The recombination landscape of the zebra finch Taeniopygia guttata genome. AB - Understanding the causes and consequences of variation in the rate of recombination is essential since this parameter is considered to affect levels of genetic variability, the efficacy of selection, and the design of association and linkage mapping studies. However, there is limited knowledge about the factors governing recombination rate variation. We genotyped 1920 single nucleotide polymorphisms in a multigeneration pedigree of more than 1000 zebra finches (Taeniopygia guttata) to develop a genetic linkage map, and then we used these map data together with the recently available draft genome sequence of the zebra finch to estimate recombination rates in 1 Mb intervals across the genome. The average zebra finch recombination rate (1.5 cM/Mb) is higher than in humans, but significantly lower than in chicken. The local rates of recombination in chicken and zebra finch were only weakly correlated, demonstrating evolutionary turnover of the recombination landscape in birds. The distribution of recombination events was heavily biased toward ends of chromosomes, with a stronger telomere effect than so far seen in any organism. In fact, the recombination rate was as low as 0.1 cM/Mb in intervals up to 100 Mb long in the middle of the larger chromosomes. We found a positive correlation between recombination rate and GC content, as well as GC-rich sequence motifs. Levels of linkage disequilibrium (LD) were significantly higher in regions of low recombination, showing that heterogeneity in recombination rates have left a footprint on the genomic landscape of LD in zebra finch populations. PMID- 20357053 TI - Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds. AB - We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome-wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNA MHM (male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) near MHM, the zebra finch Z chromosome appears to lack the MHM sequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression near MHM similar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near the MHM region of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms. PMID- 20357054 TI - Detection of Latin American strains of Histoplasma in a murine model by use of a commercially available antigen test. AB - During a Histoplasma outbreak in a colony of fruit bats at a southern United States zoo, it was observed that although Histoplasma was recovered in culture from multiple sites at necropsy, none of the samples collected from those bats tested positive for Histoplasma antigen (HAg). Five of the Histoplasma isolates from the bats were subsequently identified as Latin American (LA) clade A, restriction fragment length polymorphism (RFLP) class 6. These observations raised concern as to whether the commercially available HAg test could detect Histoplasma antigen not of the North American clade upon which the HAg test had been developed. To evaluate this concern, a murine model of disseminated histoplasmosis was established, and mice were infected with multiple LA Histoplasma isolates, including clinical isolates recovered from Brazilian AIDS patients (RFLP class 5 and class 6) and isolates recovered from the bats during the outbreak (RFLP class 6). Histoplasma antigen was detected in all infected mice in our experiments, even when Histoplasma was not recovered in culture. Because the currently available HAg test is able to detect Histoplasma antigen in mice infected with Latin American isolates, this suggests that bat host factors rather than differences among Histoplasma RFLP classes were responsible for the inability to detect HAg in infected bats. PMID- 20357055 TI - Protein-specific analysis of humoral immune responses in a clinical trial for vaccines against contagious bovine pleuropneumonia. AB - Specific humoral immune responses in a clinical trial on cattle for vaccines against contagious bovine pleuropneumonia (CBPP) were investigated. The trial included a subunit vaccine consisting of five recombinant putative variable surface proteins of the infectious agent Mycoplasma mycoides subsp. mycoides small colony type (M. mycoides SC) compared to the currently approved attenuated vaccine strain T1/44 and untreated controls. Humoral immune responses to 65 individual recombinant surface proteins of M. mycoides SC were monitored by a recently developed bead-based array assay. Responses to the subunit vaccine components were found to be weak. Animals vaccinated with this vaccine were not protected and had CBPP lesions similar to those of the untreated controls. In correlating protein-specific humoral responses to T1/44-induced immunity, five proteins associated with a protective immune response were identified by statistical evaluation, namely, MSC_1046 (LppQ), MSC_0271, MSC_0136, MSC_0079, and MSC_0431. These five proteins may be important candidates in the development of a novel subunit vaccine against CBPP. PMID- 20357056 TI - Synergic effect of genotype changes in pertussis toxin and pertactin on adaptation to an acellular pertussis vaccine in the murine intranasal challenge model. AB - The Bordetella pertussis pertussis toxin and pertactin (Prn) are protective antigens and are contained in acellular pertussis vaccines. Polymorphisms in the A subunit of pertussis toxin (PtxA) and pertactin have been proposed to mediate vaccine resistance and contribute to pertussis reemergence. To test this hypothesis, previous studies compared clinical isolates expressing different alleles for the proteins. However, other virulence factors or virulence factor expression levels also may vary, confounding the analysis. To overcome these limitations, we constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains. These results suggest that an allele shift to the ptxA1 prn2 genotype may play a role in the emergence of pertussis in vaccinated populations. PMID- 20357057 TI - Positive deamidated gliadin peptide antibodies and negative tissue transglutaminase IgA antibodies in a pediatric population: to biopsy or not to biopsy. AB - Reports from our clinical laboratory database show that 75% of children <2 years old tested for celiac serology who were found positive for deamidated gliadin peptide (DGP) antibodies had negative results for tissue transglutaminase IgA. DGP levels were shown to decline and disappear without a gluten-free diet. This observation questions DGP's specificity for diagnosis of celiac disease. PMID- 20357058 TI - Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system. AB - Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine. PMID- 20357059 TI - Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant. AB - Novel immunization strategies are needed to enhance the global control of tuberculosis (TB). In this study, we assessed the immunizing activity of a recombinant modified vaccinia Ankara (MVA) construct (MVA/IL-15/5Mtb) which overexpresses five Mycobacterium tuberculosis antigens (antigen 85A, antigen 85B, ESAT6, HSP60, and Mtb39), as well as the molecular adjuvant interleukin-15 (IL 15). Homologous prime/boost studies showed that the MVA/IL-15/5Mtb vaccine induced moderate but highly persistent protective immune responses for at least 16 months after the initial vaccination and that the interval between the prime and boost did not significantly alter vaccine-induced antituberculosis protective immunity. At 16 months, when the Mycobacterium bovis BCG and MVA/IL-15/5Mtb vaccine-induced protection was essentially equivalent, the protective responses after a tuberculous challenge were associated with elevated levels of gamma interferon (IFN-gamma), IL-17F, Cxcl9, and Cxcl10. To amplify the immunizing potential of the MVA/IL-15/5Mtb vaccine, a heterologous prime/boost regimen was tested using an ESAT6-antigen 85B (E6-85) fusion protein formulated in dimethyldiotacylammonium bromide/monophosphoryl lipid A (DDA/MPL) adjuvant as the priming vaccine and the MVA/IL-15/5Mtb recombinant virus as the boosting agent. When MVA/IL-15/5Mtb vaccine boosting was done at 2 or 6 months following the final fusion protein injections, the prime/boost regimen evoked protective responses against an aerogenic M. tuberculosis challenge which was equivalent to that induced by BCG immunization. Long-term memory after immunization with the E6 85-MVA/IL-15/5Mtb combination regimen was associated with the induction of monofunctional CD4 and CD8 IFN-gamma-producing T cells and multifunctional CD4 and CD8 T cells expressing IFN-gamma/tumor necrosis factor alpha (TNF-alpha), TNF alpha/IL-2, and IFN-gamma/TNF-alpha/IL-2. In contrast, BCG-induced protection was characterized by fewer CD4 and CD8 monofunctional T cells expressing IFN-gamma and only IFN-gamma/TNF-alpha and IFN-gamma/TNF-alpha/IL-2 expressing multifunctional T (MFT) cells. Taken together, these results suggest that a heterologous prime/boost protocol using an MVA-based tuberculosis vaccines to boost after priming with TB protein/adjuvant preparations should be considered when designing long-lived TB immunization strategies. PMID- 20357061 TI - Heterogeneous response dynamics in retinal ganglion cells: the interplay of predictive coding and adaptation. AB - To make efficient use of their limited signaling capacity, sensory systems often use predictive coding. Predictive coding works by exploiting the statistical regularities of the environment--specifically, by filtering the sensory input to remove its predictable elements, thus enabling the neural signal to focus on what cannot be guessed. To do this, the neural filters must remove the environmental correlations. If predictive coding is to work well in multiple environments, sensory systems must adapt their filtering properties to fit each environment's statistics. Using the visual system as a model, we determine whether this happens. We compare retinal ganglion cell dynamics in two very different environments: white noise and natural. Because natural environments have more power than that of white noise at low temporal frequencies, predictive coding is expected to produce a suppression of low frequencies and an enhancement of high frequencies, compared with the behavior in a white-noise environment. We find that this holds, but only in part. First, predictive coding behavior is not uniform: most on cells manifest it, whereas off cells, on average, do not. Overlaid on this nonuniformity between cell classes is further nonuniformity within both cell classes. These findings indicate that functional considerations beyond predictive coding play an important role in shaping the dynamics of sensory adaptation. Moreover, the differences in behavior between on and off cell classes add to the growing evidence that these classes are not merely homogeneous mirror images of each other and suggest that their roles in visual processing are more complex than expected from the classic view. PMID- 20357060 TI - Fatigue and motor redundancy: adaptive increase in finger force variance in multi finger tasks. AB - We studied the effects of fatigue of the index finger on indices of force variability in discrete and rhythmic accurate force production tasks performed by the index finger and by all four fingers pressing in parallel. An increase in the variance of the force produced by the fatigued index finger was expected. We hypothesized that the other fingers would also show increased variance of their forces, which would be accompanied by co-variation among the finger forces resulting in relatively preserved accuracy of performance. The subjects performed isometric tasks including maximal voluntary contraction (MVC) and accurate force production before and after a 1-min MVC fatiguing exercise by the index finger. During fatigue, there was a significant increase in the root mean square index of force variability during accurate force production by the index finger. In the four-finger tasks, the variance of the individual finger force increased for all four fingers, while the total force variance showed only a modest change. We quantified two components of variance in the space of hypothetical commands to fingers, finger modes. There was a large increase in the variance component that did not affect total force and a much smaller increase in the component that did. The results suggest an adaptive increase in force variance by nonfatigued elements as a strategy to attenuate effects of fatigue on accuracy of multi element performance. These effects were unlikely to originate at the level of synchronization of motor units across muscle compartments but rather involved higher control levels. PMID- 20357062 TI - Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain. AB - Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the auditory midbrain increases neural discrimination of complex vocalizations. PMID- 20357063 TI - Abnormal anterior pretectal nucleus activity contributes to central pain syndrome. AB - Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS. PMID- 20357065 TI - Kinetics of fast short-term depression are matched to spike train statistics to reduce noise. AB - Short-term depression (STD) is observed at many synapses of the CNS and is important for diverse computations. We have discovered a form of fast STD (FSTD) in the synaptic responses of pyramidal cells evoked by stimulation of their electrosensory afferent fibers (P-units). The dynamics of the FSTD are matched to the mean and variance of natural P-unit discharge. FSTD exhibits switch-like behavior in that it is immediately activated with stimulus intervals near the mean interspike interval (ISI) of P-units (approximately 5 ms) and recovers immediately after stimulation with the slightly longer intervals (>7.5 ms) that also occur during P-unit natural and evoked discharge patterns. Remarkably, the magnitude of evoked excitatory postsynaptic potentials appear to depend only on the duration of the previous ISI. Our theoretical analysis suggests that FSTD can serve as a mechanism for noise reduction. Because the kinetics of depression are as fast as the natural spike statistics, this role is distinct from previously ascribed functional roles of STD in gain modulation, synchrony detection or as a temporal filter. PMID- 20357064 TI - Manipulation after object rotation reveals independent sensorimotor memory representations of digit positions and forces. AB - Planning of object manipulations is dependent on the ability to generate, store, and retrieve sensorimotor memories of previous actions associated with grasped objects. However, the sensorimotor memory representations linking object properties to the planning of grasp are not well understood. Here we use an object rotation task to gain insight into the mechanisms underlying the nature of these sensorimotor memories. We asked subjects to grasp a grip device with an asymmetrical center of mass (CM) anywhere on its vertical surfaces and lift it while minimizing object roll. After subjects learned to minimize object roll by generating a compensatory moment, they were asked to rotate the object 180 degrees about a vertical axis and lift it again. The rotation resulted in changing the direction of external moment opposite to that experienced during the prerotation block. Anticipatory grasp control was quantified by measuring the compensatory moment generated at object lift onset by thumb and index finger forces through their respective application points. On the first postrotation trial, subjects failed to generate a compensatory moment to counter the external moment caused by the new CM location, thus resulting in a large object roll. Nevertheless, after several object rotations subjects reduced object roll on the initial postrotation trials by anticipating the new CM location through the modulation of digit placement but not tangential forces. The differential improvement in modulating these two variables supports the notion of independent memory representations of kinematics and kinetics and is discussed in relation to neural mechanisms underlying visuomotor transformations. PMID- 20357066 TI - Proximodistal gradient in the perception of delayed stiffness. AB - Proximal and distal muscles are different in size, maximum force, mechanical action, and neuromuscular control. In the current study we explore the perception of delayed stiffness when probing is executed using movement of different joints. We found a proximodistal gradient in the amount of underestimation of delayed stiffness in the transition between probing with shoulder, elbow, and wrist joints. Moreover, there was a similar gradient in the optimal weighting between estimation of stiffness and the inverse of estimation of compliance that predicted the perception of the subjects. These gradients could not be ascribed to differences in movement amplitude, duration, velocity, and force amplitude because these variables were not significantly modulated by the joint used for probing. Mean force did not follow a similar gradient either. Therefore we suggest that the observed gradient in perception reveals a proximodistal gradient in control, such that proximal joints are dominated by force control, whereas distal joints are dominated by position control. PMID- 20357067 TI - Nociceptive processing by anterior cingulate pyramidal neurons. AB - Although the cingulate cortex is frequently activated in acute human pain studies, postsynaptic responses are not known nor are links between nociceptive afferents, neuronal responses, and outputs to other structures. Intracellular potentials were recorded from neurobiotin-injected, pyramidal neurons in anterior cingulate area 24b following noxious stimulation of the sciatic nerve in anesthetized rabbits. Layer IIIc pyramids had extensive and horizontally oriented basal dendrites in layer IIIc where nociceptive afferents terminate. They had the longest excitatory postsynaptic potentials (EPSPs; 545 ms) that were modulated with hyperpolarizing currents. Pyramids in layer V had an intermediate tuft of oblique apical dendrites in layer IIIc that were 150-350 microm from somata in layer Va and 351-550 microm in layer Vb. Although average EPSP durations were short in layers II-IIIab (222 +/- 31), Va (267 +/- 65), and Vb (159 +/- 31), there were five neurons in layers IIIab-Va that had EPSP durations lasting >300 ms (548 +/- 63 ms). Neurons in layers IIIc, Va, and Vb had the highest amplitude EPSPs (6.25, 6.84 +/- 0.58, and 6.4 +/- 0.47 mV, respectively), whereas those in layers II-IIIab were 5 +/- 0.56 mV. Nociceptive responses in layer Vb were complex and some had initial inhibitory postsynaptic potentials with shorter duration EPSPs. Layers II-IIIab had dye-coupled pyramids and EPSPs in these layers had short durations (167 +/- 33 ms) compared with those in layers IIIc-Va (487 +/- 28 ms). In conclusion there are two populations of anterior cingulate cortex pyramids with EPSPs of significantly different durations, although their dendritic morphologies do not predict EPSP duration. Short-duration EPSPs are thalamic-mediated, nociceptive responses lasting < or =200 ms. Longer, "integrative" EPSPs are >350 ms and are likely modulated by intracortical axon collateral discharges. These findings suggest that links between nociception and projections to cortical and motor systems are instantaneous because nociceptive responses are generated directly by pyramidal projection neurons in all layers. PMID- 20357068 TI - Learning not to generalize: modular adaptation of visuomotor gain. AB - When a new sensorimotor mapping is learned through practice, learning commonly transfers to unpracticed regions of task space, that is, generalization ensues. Does generalization reflect fixed properties of movement representations in the nervous system and thereby limit what visuomotor mappings can and cannot be learned? Or does what needs to be learned determine the shape of generalization? We used the broad generalization properties of visuomotor gain adaptation to address these questions. Adaptation to a single gain for reaching movements is known to generalize broadly across movement directions. By training subjects on two different gains in two directions, we set up a potential conflict between generalization patterns: if generalization of gain adaptation indicates fixed properties of movement amplitude encoding, then learning two different gains in different directions should not be possible. Conversely, if generalization is flexible, then it should be possible to learn two gains. We found that subjects were able to learn two gains simultaneously, although more slowly than when they adapted to a single gain. Analysis of the resulting double-gain generalization patterns, however, unexpectedly revealed that generalization around each training direction did not arise de novo, but could be explained by a weighted combination of single-gain generalization patterns, in which the weighting takes into account the relative angular separation between training directions. Our findings therefore demonstrate that the mappings to each training target can be fully learned through reweighting of single-gain generalization patterns and not through a categorical alteration of these functions. These results are consistent with a modular decomposition approach to visuomotor adaptation, in which a complex mapping results from a combination of simpler mappings in a "mixture-of experts" architecture. PMID- 20357069 TI - Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields. AB - The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network. PMID- 20357070 TI - Differences in Na+ conductance density and Na+ channel functional properties between dopamine and GABA neurons of the rat substantia nigra. AB - Dopamine (DA) neurons and GABA neurons of the substantia nigra (SN) promote distinct functions in the control of movement and have different firing properties and action potential (AP) waveforms. APs recorded from DA and GABA neurons differed in amplitude, maximal rate of rise, and duration. In addition, the threshold potential for APs was higher in DA neurons than in GABA neurons. The activation of voltage-gated Na(+) channels accounts largely for these differences as the application of a low concentration of the voltage-gated Na(+) channel blocker TTX had an effect on all of these parameters. We have examined functional properties of somatic Na(+) channels in nucleated patches isolated from DA and GABA neurons. Peak amplitudes of macroscopic Na(+) currents were smaller in DA neurons in comparison to those in GABA neurons. The mean peak Na(+) conductance density was 24.5 pS microm(-2) in DA neurons and almost twice as large, 41.6 pS microm(-2), in GABA neurons. The voltage dependence of Na(+) channel activation was not different between the two types of SN neurons. Na(+) channels in DA and GABA neurons, however, differed in the voltage dependence of inactivation, the mean mid-point potential of steady-state inactivation curve being more positive in DA neurons than in GABA neurons. The results suggest that specific Na(+) channel gating properties and Na(+) conductance densities in the somatic membrane of SN neurons may have consequences on synaptic signal integration in the soma of both types of neurons and on somatodendritic release of dopamine by DA neurons. PMID- 20357071 TI - Effects of category-specific costs on neural systems for perceptual decision making. AB - Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category specific cost in keeping with the hypothesis that loss functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between perception and action, expressed via general effects on frontal cortex, and selective effects on extrastriate cortex. These findings indicate that asymmetric costs may affect a neural implementation of perceptual decision making in a similar manner to changes in category expectation, constituting a step toward accounting for how prospective losses are flexibly integrated with sensory evidence in the brain. PMID- 20357072 TI - Expression of neuronal nitric oxide synthase in rabbit carotid body glomus cells regulates large-conductance Ca2+-activated potassium currents. AB - Our previous studies show that a decrease in endogenous nitric oxide (NO) is involved in the blunted outward K(+) currents in carotid body (CB) glomus cells from chronic heart failure (CHF) rabbits. In the present study, we measured the effects of the neuronal nitric oxide synthase (nNOS) transgene on the K(+) currents in CB glomus cells from pacing-induced CHF rabbits. Using single-cell real-time RT-PCR and immunofluorescent techniques, we found that nNOS mRNA and protein are expressed in the rabbit CB glomus cells and CHF decreased the expression of nNOS mRNA and protein in CB glomus cells. After 3 days of an adenoviral nNOS (Ad.nNOS) gene transfection, the expression of nNOS protein was increased to the level found in sham CB glomus cells. In whole cell patch-clamp experiments, Ad.nNOS markedly reversed the attenuated K(+) currents in CB glomus cells from CHF rabbits. The specific nNOS inhibitor (S-methyl-l-thiocitrulline [SMTC]) and large-conductance Ca(2+)-activated K(+) (BK) channel blocker (iberiotoxin) fully abolished the effect of Ad.nNOS on the K(+) currents in the CB glomus cells from CHF rabbits. However, neither CHF nor Ad.nNOS altered the protein expression of BK channel alpha-subunit. These results suggest that a decrease of NO induced by an attenuated nNOS activity lowers the activation of the BK channels but not the protein expression of the BK channel alpha-subunit in the CB glomus cells during CHF. PMID- 20357074 TI - Role of the rostral superior colliculus in gaze anchoring during reach movements. AB - When reaching for an object, primates usually look at their target before touching it with the hand. This gaze movement prior to the arm movement allows target fixation, which is usually prolonged until the target is reached. In this manner, a stable image of the object is provided on the fovea during the reach, which is crucial for guiding the final part of the hand trajectory by visual feedback. Here we investigated a neural substrate possibly responsible for this behavior. In particular we tested the influence of reaching movements on neurons recorded at the rostral pole of the superior colliculus (rSC), an area classically related to fixation. Most rSC neurons showed a significant increase in their activity during reaching. Moreover, this increase was particularly high when the reaching movements were preceded by corresponding saccades to the targets to be reached, probably revealing a stronger coupling of the oculo-manual neural system during such a natural task. However, none of the parameters tested- including movement kinematics and target location--was found to be closely related to the observed increase in neural activity. Thus the increase in activity during reaching was found to be rather nonspecific except for its dependence on whether the reach was produced in isolation or in combination with a gaze movement. These results identify the rSC as a neural substrate sufficient for gaze anchoring during natural reaching movements, placing its activity at the core of the neural system dedicated to eye-hand coordination. PMID- 20357073 TI - Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. AB - Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease. PMID- 20357076 TI - Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva. PMID- 20357075 TI - Phase-dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury. AB - Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11-Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals. PMID- 20357077 TI - Pistachios increase serum antioxidants and lower serum oxidized-LDL in hypercholesterolemic adults. AB - Pistachios are high in lutein, beta-carotene, and gamma-tocopherol relative to other nuts; however, studies of the effects of pistachios on oxidative status are lacking. We conducted a randomized, crossover controlled-feeding study to evaluate 2 doses of pistachios on serum antioxidants and biomarkers of oxidative status in 28 hypercholesterolemic adults (LDL-cholesterol >or=2.86 mmol/L). Participants consumed 3 isoenergetic diets for 4 wk each after a 2-wk baseline Western diet. Experimental diets included a lower-fat control diet without pistachios (25% total fat) with 1 serving/d (i.e. 32-63 g/d; energy adjusted) of pistachios (1 PD; 10% energy from pistachios; 30% total fat) or with 2 servings/d (63-126 g/d; energy adjusted) of pistachios (2 PD; 20% energy from pistachios; 34% total fat). When participants consumed the pistachio-enriched diets, they had higher plasma lutein (P < 0.0001), alpha-carotene, and beta-carotene (P < 0.01) concentrations than after the baseline diet. After consuming the pistachio diets, participants had greater plasma lutein (P < 0.001) and gamma-tocopherol (P < 0.05; 2 PD only) relative to the lower-fat control diet. After the 2 PD diet period, participants also had lower serum oxidized-LDL concentrations than following the baseline diet period (P < 0.05). After both the 1 PD and 2 PD diet periods, they had lower serum oxidized-LDL concentrations than after the control diet period (P < 0.05). The change in oxidized-LDL from baseline correlated positively with the change in LDL-cholesterol across all treatments (r = 0.42; P < 0.005). After controlling for the change in serum LDL-cholesterol as a covariate, increases in serum lutein and gamma-tocopherol following the 2 PD period were still modestly associated with decreases in oxidized-LDL (r = -0.36, P = 0.06 and r = -0.35, P = 0.08, respectively). This suggests that a heart healthy diet including pistachios contributes to the decrease in the serum oxidized-LDL concentration through cholesterol-lowering and may provide an added benefit as a result of the antioxidants the pistachios contain. PMID- 20357078 TI - Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells. AB - The following proteins are candidates for maintaining biotin homeostasis in humans: the biotin transporters sodium-dependent multivitamin transporter (SMVT) and monocarboxylate transporter 1, the biotinyl-protein ligase holocarboxylase synthetase (HCS), and the lysine-epsilon-biotin hydrolase biotinidase. Liver cells are supplied through the portal vein with high levels of water-soluble vitamins compared with those of peripheral tissues. We hypothesized that the mechanisms of biotin homeostasis are qualitatively and quantitatively different in cells derived from human liver (HepG2 cells) and lymphoid tissues (Jurkat cells). Cells were cultured in biotin-defined media, representing deficient (D), normal (N), and supplemented (S) individuals. Biotinylation of carboxylases depended on biotin availability in both cell types, but HepG2 cells required 3 times more biotin than Jurkat cells to maintain normal levels of holocarboxylases. The expression of biotin transporters was less in both types in medium S compared with cells in media D and N; in contrast, the expression of HCS was higher in cells in medium S compared with the other cells. The abundance of 3 methylcrotonyl-CoA carboxylase mRNA was lower in cells in medium D than cells in media N and S. The enrichment of biotinylated histones was higher at the SMVT promoter 1 in HepG2 and Jurkat cells in medium S compared with the corresponding cells in media D and N, presumably repressing the SMVT gene. The mechanisms of biotin homeostasis are qualitatively similar but quantitatively different in HepG2 and Jurkat cells; HCS, histone biotinylation, and biotin transporters play a role in homeostasis in both. PMID- 20357080 TI - Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype. AB - Dietary choline deprivation (CD) is associated with behavioral changes, but mechanisms underlying these detrimental effects are not well characterized. For instance, no literature data are available concerning the CD effects on brain mitochondrial function related to impairment in cognition. Therefore, we investigated brain mitochondrial function and redox status in male Wistar rats fed a CD diet for 28 d. Moreover, the CD behavioral phenotype was characterized. Compared with rats fed a control diet (CTRL), CD rats showed lower NAD-dependent mitochondrial state III and state IV respiration, 40% lower complex I activity, and significantly higher reactive oxygen species production. Total glutathione was oxidatively consumed more in CD than in CTRL rats and the rate of protein oxidation was 40% higher in CD than in CTRL rats, reflecting an oxidative stress condition. The mitochondrial concentrations of cardiolipin, a phospholipid required for optimal activity of complex I, was 20% lower in CD rats than in CTRL rats. Compared with CTRL rats, the behavioral phenotype of CD rats was characterized by impairment in motor coordination and motor learning assessed with the rotarod/accelerod test. Furthermore, compared with CTRL rats, CD rats were less capable of learning the active avoidance task and the number of attempts they made to avoid foot shock was fewer. The results suggest that CD induced dysfunction in brain mitochondria may be responsible for impairment in cognition and underline that, similar to the liver, the brain also needs an adequate choline supply for its normal functioning. PMID- 20357079 TI - Growing rats respond to a sulfur amino acid-deficient diet by phosphorylation of the alpha subunit of eukaryotic initiation factor 2 heterotrimeric complex and induction of adaptive components of the integrated stress response. AB - Mammalian cells respond to various kinds of stress, including nutritional stress, via pathways that are initiated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 complex (eIF2alpha). Because the models used to study eIF2alpha-kinase-mediated responses to amino acid deficiency have commonly used media or diets devoid of 1 or more essential amino acids, we asked whether eIF2alpha-kinase-mediated responses would be induced in animals fed a more typical diet that was not as imbalanced as one in which 1 essential amino acid is totally absent. To answer this question, we fed rats soy protein-based diets that were either adequate or limiting in sulfur-containing amino acids (SAA). Rats fed a SAA-deficient diet (3.4 g methionine equivalents/kg diet) grew more slowly than rats fed the control diet (5.86 g methionine equivalents/kg diet). Analysis of liver from rats fed these diets for 7 d showed that the SAA-deficient rats had higher levels of eIF2alpha phosphorylation and higher levels of activating transcription factor (ATF) 4, ATF3, asparagine synthetase, solute carrier 7A11, cysteinyl-tRNA synthetase, and cystathionine gamma-lyase. On the other hand, components of the integrated stress response (ISR) known to promote apoptosis or translational recovery were not induced. Taken together, our results indicate that rats fed the SAA-deficient diet had a prolonged activation of an eIF2alpha kinase that leads to upregulation of adaptive components of the ISR. PMID- 20357081 TI - Intake of trans fatty acids causes nonalcoholic steatohepatitis and reduces adipose tissue fat content. AB - We investigated the effects of dietary trans fatty acids, PUFA, and SFA on body and liver fat content, liver histology, and mRNA of enzymes involved in fatty acid metabolism. LDL receptor knockout weaning male mice were fed for 16 wk with diets containing 40% energy as either trans fatty acids (TRANS), PUFA, or SFA. Afterwards, subcutaneous and epididymal fat were weighed and histological markers of nonalcoholic fatty liver disease (NAFLD) were assessed according to the Histological Scoring System for NAFLD. PPARalpha, PPARgamma, microsomal triglyceride transfer protein (MTP), carnitine palmitoyl transferase 1 (CPT-1), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA were measured by quantitative RT-PCR. Food intake was similar in the 3 groups, although mice fed the TRANS diet gained less weight than those receiving the PUFA diet. Compared with the PUFA- and SFA-fed mice, TRANS-fed mice had greater plasma total cholesterol (TC) and triglyceride (TG) concentrations, less epididymal and subcutaneous fat, larger livers with nonalcoholic steatohepatitis (NASH)-like lesions, and greater liver TC and TG concentrations. Macrosteatosis in TRANS-fed mice was associated with a higher homeostasis model assessment of insulin resistance (HOMA(IR)) index and upregulated mRNA related to hepatic fatty acid synthesis (SREBP-1c and PPARgamma) and to downregulated MTP mRNA. Diet consumption did not alter hepatic mRNA related to fatty acid oxidation (PPARalpha and CPT-1). In conclusion, compared with PUFA- and SFA-fed mice, TRANS-fed mice had less adiposity, impaired glucose tolerance characterized by greater HOMA(IR) index, and NASH-like lesions due to greater hepatic lipogenesis. These results demonstrate the role of trans fatty acid intake on the development of key features of metabolic syndrome. PMID- 20357082 TI - Teaching internal medicine residents quality improvement and patient safety: a lean thinking approach. AB - Patient safety (PS) and quality improvement (QI) are among the highest priorities for all health systems. Resident physicians are often at the front lines of providing care for patients. In many instances, however, QI and PS initiatives exclude trainees. By aligning the goals of the health system with those of the residency program to engage residents in QI and PS projects, there is a unique opportunity to fulfill both a corporate and educational mission to improve patient care. Here, the authors briefly describe one residency program's educational curriculum to provide foundational knowledge in QI and PS to all its trainees and highlight a resident team-based project that applied principles of lean thinking to evaluate the process of responding to an in-hospital cardiopulmonary arrest. This approach provided residents with a practical experience but also presented an opportunity for trainees to align with the health system's approach to improving quality and safety. PMID- 20357083 TI - Coinfection of hepatic cell lines with human immunodeficiency virus and hepatitis B virus leads to an increase in intracellular hepatitis B surface antigen. AB - Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals. PMID- 20357084 TI - Combinatorial latency reactivation for HIV-1 subtypes and variants. AB - The eradication of HIV-1 will likely require novel clinical approaches to purge the reservoir of latently infected cells from a patient. We hypothesize that this therapy should target a wide range of latent integration sites, act effectively against viral variants that have acquired mutations in their promoter regions, and function across multiple HIV-1 subtypes. By using primary CD4(+) and Jurkat cell-based in vitro HIV-1 latency models, we observe that single-agent latency reactivation therapy is ineffective against most HIV-1 subtypes. However, we demonstrate that the combination of two clinically promising drugs-namely, prostratin and suberoylanilide hydroxamic acid (SAHA)-overcomes the limitations of single-agent approaches and can act synergistically for many HIV-1 subtypes, including A, B, C, D, and F. Finally, by identifying the proviral integration position of latent Jurkat cell clones, we demonstrate that this drug combination does not significantly enhance the expression of endogenous genes nearest to the proviral integration site, indicating that its effects may be selective. PMID- 20357085 TI - Viral entry inhibitors targeted to the membrane site of action. AB - The fusion of enveloped viruses with the host cell is driven by specialized fusion proteins to initiate infection. The "class I" fusion proteins harbor two regions, typically two heptad repeat (HR) domains, which are central to the complex conformational changes leading to fusion: the first heptad repeat (HRN) is adjacent to the fusion peptide, while the second (HRC) immediately precedes the transmembrane domain. Peptides derived from the HR regions can inhibit fusion, and one HR peptide, T20 (enfuvirtide), is in clinical use for HIV-1. For paramyxoviruses, the activities of two membrane proteins, the receptor-binding protein (hemagglutinin-neuraminidase [HN] or G) and the fusion protein (F), initiate viral entry. The binding of HN or G to its receptor on a target cell triggers the activation of F, which then inserts into the target cell and mediates the membrane fusion that initiates infection. We have shown that for paramyxoviruses, the inhibitory efficacy of HR peptides is inversely proportional to the rate of F activation. For HIV-1, the antiviral potency of an HRC-derived peptide can be dramatically increased by targeting it to the membrane microdomains where fusion occurs, via the addition of a cholesterol group. We report here that for three paramyxoviruses-human parainfluenza virus type 3 (HPIV3), a major cause of lower respiratory tract diseases in infants, and the emerging zoonotic viruses Hendra virus (HeV) and Nipah virus (NiV), which cause lethal central nervous system diseases-the addition of cholesterol to a paramyxovirus HRC-derived peptide increased antiviral potency by 2 log units. Our data suggest that this enhanced activity is indeed the result of the targeting of the peptide to the plasma membrane, where fusion occurs. The cholesterol-tagged peptides on the cell surface create a protective antiviral shield, target the F protein directly at its site of action, and expand the potential utility of inhibitory peptides for paramyxoviruses. PMID- 20357086 TI - The Rab11 pathway is required for influenza A virus budding and filament formation. AB - Influenza A virus buds through the apical plasma membrane, forming enveloped virus particles that can take the shape of pleomorphic spheres or vastly elongated filaments. For either type of virion, the factors responsible for separation of viral and cell membranes are not known. We find that cellular Rab11 (a small GTP-binding protein involved in endocytic recycling) and Rab11-family interacting protein 3 ([FIP3] which plays a role in membrane trafficking and regulation of actin dynamics) are both required to support the formation of filamentous virions, while Rab11 is additionally involved in the final budding step of spherical particles. Cells transfected with Rab11 GTP-cycling mutants or depleted of Rab11 or FIP3 content by small interfering RNA treatment lost the ability to form virus filaments. Depletion of Rab11 resulted in up to a 100-fold decrease in titer of spherical virus released from cells. Scanning electron microscopy of Rab11-depleted cells showed high densities of virus particles apparently stalled in the process of budding. Transmission electron microscopy of thin sections confirmed that Rab11 depletion resulted in significant numbers of abnormally formed virus particles that had failed to pinch off from the plasma membrane. Based on these findings, we see a clear role for a Rab11-mediated pathway in influenza virus morphogenesis and budding. PMID- 20357087 TI - Route of adenovirus-based HIV-1 vaccine delivery impacts the phenotype and trafficking of vaccine-elicited CD8+ T lymphocytes. AB - Candidate HIV-1 vaccine regimens utilizing intramuscularly (i.m.) administered recombinant adenovirus (rAd)-based vectors can induce potent mucosal cellular immunity. However, the degree to which mucosal rAd vaccine routing might alter the quality and anatomic distribution of vaccine-elicited CD8(+) T lymphocytes remains unclear. We show that the route of vaccination critically impacts not only the magnitude but also the phenotype and trafficking of antigen-specific CD8(+) T lymphocytes in mice. I.m. rAd immunization induced robust local transgene expression and elicited high-frequency, polyfunctional CD8(+) T lymphocytes that trafficked broadly to both systemic and mucosal compartments. In contrast, intranasal (i.n.) rAd immunization led to similarly robust local transgene expression but generated low-frequency, monofunctional CD8(+) T lymphocytes with restricted anatomic trafficking patterns. Respiratory rAd immunization elicited systemic and mucosal CD8(+) T lymphocytes with phenotypes and trafficking properties distinct from those elicited by i.m. or i.n. rAd immunization. Our findings indicate that the anatomic microenvironment of antigen expression critically impacts the phenotype and trafficking of antigen-specific CD8(+) T lymphocytes. PMID- 20357088 TI - Making sense of antisense: seemingly noncoding RNAs antisense to the master regulator of Kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mRNAs encoding small peptides. AB - The mammalian transcriptome is studded with putative noncoding RNAs, many of which are antisense to known open reading frames (ORFs). Roles in the regulation of their complementary mRNAs are often imputed to these antisense transcripts, but few have been experimentally examined, and such functions remain largely conjectural. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two transcripts that lack obvious ORFs and are complementary to the gene (RTA) encoding the master regulator of the latent/lytic switch. Here, we show that, contrary to expectation, these RNAs do not regulate RTA expression. Rather, they are found on polysomes, and genetic analysis indicates that translational initiation occurs at several AUG codons in the RNA, leading to the presumptive synthesis of peptides of 17 to 48 amino acids. These findings underscore the need for circumspection in the computational assessment of coding potential and raise the possibility that the mammalian proteome may contain many previously unsuspected peptides generated from seemingly noncoding RNAs, some of which could have important biological functions. Irrespective of their function, such peptides could also contribute substantially to the repertoire of T cell epitopes generated in both uninfected and infected cells. PMID- 20357089 TI - Evidence for translational regulation by the herpes simplex virus virion host shutoff protein. AB - The herpes simplex virus (HSV) virion host shutoff protein (vhs) encoded by gene UL41 is an mRNA-specific RNase that triggers accelerated degradation of host and viral mRNAs in infected cells. We report here that vhs is also able to modulate reporter gene expression without greatly altering the levels of the target mRNA in transient-transfection assays conducted in HeLa cells. We monitored the effects of vhs on a panel of bicistronic reporter constructs bearing a variety of internal ribosome entry sites (IRESs) located between two test cistrons. As expected, vhs inhibited the expression of the 5' cistrons of all of these constructs; however, the response of the 3' cistron varied with the IRES: expression driven from the wild-type EMCV IRES was strongly suppressed, while expression controlled by a mutant EMCV IRES and the cellular ApaF1, BiP, and DAP5 IRES elements was strongly activated. In addition, several HSV type 1 (HSV-1) 5' untranslated region (5' UTR) sequences also served as positive vhs response elements in this assay. IRES activation was also observed in 293 and HepG2 cells, but no such response was observed in Vero cells. Mutational analysis has yet to uncouple the ability of vhs to activate 3' cistron expression from its shutoff activity. Remarkably, repression of 5' cistron expression could be observed under conditions where the levels of the reporter RNA were not correspondingly reduced. These data provide strong evidence that vhs can modulate gene expression at the level of translation and that it is able to activate cap-independent translation through specific cis-acting elements. PMID- 20357090 TI - Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection. AB - During primary infection, the number of HIV-1 particles in plasma increases rapidly, reaches a peak, and then declines until it reaches a set point level. Understanding the kinetics of primary infection, and its effect on the establishment of chronic infection, is important in defining the early pathogenesis of HIV. We studied the viral dynamics of very early HIV-1 infection in 47 subjects identified through plasma donation screening. We calculated how fast the viral load increases and how variable this parameter is among individuals. We also estimated the basic reproductive ratio, the number of new infected cells generated by an infectious cell at the start of infection when target cells are not limiting. The initial viral doubling time had a median of 0.65 days with an interquartile range of 0.56 to 0.91 days. The median basic reproductive ratio was 8.0 with an interquartile range of 4.9 to 11. In 15 patients, we also observed the postpeak decay of plasma virus and found that the virus decay occurred at a median rate of 0.60 day(-1), corresponding to a half life of 1.2 days. The median peak viral load was 5.8 log(10) HIV-1 RNA copies/ml, and it was reached 14 days after the virus was quantifiable with an assay, with a lower limit of detection of 50 copies/ml. These results characterize the early plasma viral dynamics in acute HIV infection better than it has been possible thus far. They also better define the challenge that the immune response (or therapeutic intervention) has to overcome to defeat HIV at this early stage. PMID- 20357091 TI - Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. AB - The variability of the hepatitis C virus (HCV), which likely contributes to immune escape, is most pronounced in hypervariable region 1 (HVR1) of viral envelope protein 2. This domain is the target for neutralizing antibodies, and its deletion attenuates replication in vivo. Here we characterized the relevance of HVR1 for virus replication in vitro using cell culture-derived HCV. We show that HVR1 is dispensable for RNA replication. However, viruses lacking HVR1 (Delta HVR1) are less infectious, and separation by density gradients revealed that the population of Delta HVR1 virions comprises fewer particles with low density. Strikingly, Delta HVR1 particles with intermediate density (1.12 g/ml) are as infectious as wild-type virions, while those with low density (1.02 to 1.08 g/ml) are poorly infectious, despite quantities of RNA and core similar to those in wild-type particles. Moreover, Delta HVR1 particles exhibited impaired fusion, a defect that was partially restored by an E1 mutation (I347L), which also rescues infectivity and which was selected during long-term culture. Finally, Delta HVR1 particles were no longer neutralized by SR-B1-specific immunoglobulins but were more prone to neutralization and precipitation by soluble CD81, E2-specific monoclonal antibodies, and patient sera. These results suggest that HVR1 influences the biophysical properties of released viruses and that this domain is particularly important for infectivity of low-density particles. Moreover, they indicate that HVR1 obstructs the viral CD81 binding site and conserved neutralizing epitopes. These functions likely optimize virus replication, facilitate immune escape, and thus foster establishment and maintenance of a chronic infection. PMID- 20357092 TI - Hepatitis C virus differentially modulates activation of forkhead transcription factors and insulin-induced metabolic gene expression. AB - Chronic hepatitis C virus (HCV) infection is often associated with insulin resistance and hepatic steatosis. Insulin regulates gene expression of key enzymes in glucose and lipid metabolism by modulating the activity of specific Forkhead box transcriptional regulators (FoxO1 and FoxA2) via the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway in the liver. In this study, we observed that HCV infection of human hepatocytes impaired insulin induced FoxO1 translocation from the nucleus to the cytoplasm and significantly reduced accumulation of FoxA2 in the nucleus. Phosphorylation of FoxO1 at Ser(256), a downstream target for Akt, was inhibited in hepatocytes infected with HCV or expressing the core protein or full-length (FL) genome of HCV. Further, an interaction between FoxO1 and 14-3-3 protein, important for FoxO1 translocation, was inhibited in HCV core-expressing cells. Hepatocytes infected with HCV, expressing the core protein alone or polyprotein displayed an increased level of glucose-6-phosphatase (G6P) mRNA. On the other hand, microsomal triglycerol transfer protein (MTP) activity and apolipoprotein B (ApoB) secretion were significantly reduced in hepatocytes expressing HCV proteins. Together, these observations suggest that HCV infection or ectopic expression of the core protein either alone or together with other viral proteins from an FL gene construct differentially modulates FoxO1 and FoxA2 activation and affects insulin-induced metabolic gene regulation in human hepatocytes. PMID- 20357093 TI - Whole-genome characterization and genotyping of global WU polyomavirus strains. AB - Exploration of the genetic diversity of WU polyomavirus (WUV) has been limited in terms of the specimen numbers and particularly the sizes of the genomic fragments analyzed. Using whole-genome sequencing of 48 WUV strains collected in four continents over a 5-year period and 16 publicly available whole-genome sequences, we identified three main WUV clades and five subtypes, provisionally termed Ia, Ib, Ic, II, IIIa, and IIIb. Overall nucleotide variation was low (0 to 1.2%). The discriminatory power of the previous VP2 fragment typing method was found to be limited, and a new, larger genotyping region within the VP2/1 interface was proposed. PMID- 20357094 TI - p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha. AB - TRIM5 proteins mediate a potent block to the cross-species transmission of retroviruses, the most well known being the TRIM5alpha protein from rhesus macaques, which potently inhibits human immunodeficiency virus type 1 (HIV-1) infection. This restriction occurs at an early stage in the replication cycle and is mediated by the binding of TRIM5 proteins to determinants present in the retroviral capsid. TRIM5alpha, as well as other TRIM family proteins, has been shown to be regulated by interferons (IFN). Here we show that TRIM5alpha associates with another IFN-induced gene, sequestosome-1/p62 (p62). p62 plays a role in several signal transduction cascades that are important for maintaining the antiviral state of cells. Here we demonstrate that p62 localizes to both human and rhesus macaque TRIM5alpha cytoplasmic bodies, and fluorescence resonance energy transfer (FRET) analysis demonstrates that these proteins closely associate in these structures. When p62 expression was knocked down via small interfering RNA (siRNA), the number of TRIM5alpha cytoplasmic bodies and the level of TRIM5alpha protein expression were reduced in cell lines stably expressing epitope-tagged versions of TRIM5alpha. In accordance with these data, p62 knockdown resulted in reduced TRIM5alpha-mediated retroviral restriction in cells expressing epitope-tagged TRIM5alpha or expressing endogenously expressed human TRIM5alpha. p62 may therefore operate to enhance TRIM5alpha-mediated retroviral restriction, contributing to the antiviral state of cells following IFN treatment. PMID- 20357095 TI - Interplay of RNA elements in the dengue virus 5' and 3' ends required for viral RNA replication. AB - Dengue virus (DENV) is a member of the Flavivirus genus of positive-sense RNA viruses. DENV RNA replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5' and 3' ends, designated 5' and 3' cyclization sequences (5'-3' CS) and the 5' and 3' upstream of AUG region (5' 3' UAR). Here, we demonstrate that another stretch of six nucleotides in the 5' end is involved in DENV replication and possibly genome cyclization. This new sequence is located downstream of the AUG, designated the 5' downstream AUG region (5' DAR); the motif predicted to be complementary in the 3' end is termed the 3' DAR. In addition to the UAR, CS and DAR motifs, two other RNA elements are located at the 5' end of the viral RNA: the 5' stem-loop A (5' SLA) interacts with the viral RNA-dependent RNA polymerase and promotes RNA synthesis, and a stem-loop in the coding region named cHP is involved in translation start site selection as well as RNA replication. We analyzed the interplay of these 5' RNA elements in relation to RNA replication, and our data indicate that two separate functional units are formed; one consists of the SLA, and the other includes the UAR, DAR, cHP, and CS elements. The SLA must be located at the 5' end of the genome, whereas the position of the second unit is more flexible. We also show that the UAR, DAR, cHP, and CS must act in concert and therefore likely function together to form the tertiary RNA structure of the circularized DENV genome. PMID- 20357096 TI - Japanese encephalitis virus utilizes the canonical pathway to activate NF-kappaB but it utilizes the type I interferon pathway to induce major histocompatibility complex class I expression in mouse embryonic fibroblasts. AB - Flaviviruses have been shown to induce cell surface expression of major histocompatibility complex class I (MHC-I) through the activation of NF-kappaB. Using IKK1(-/-), IKK2(-/-), NEMO(-/-), and IKK1(-/-) IKK2(-/-) double mutant as well as p50(-/-) RelA(-/-) cRel(-/-) triple mutant mouse embryonic fibroblasts infected with Japanese encephalitis virus (JEV), we show that this flavivirus utilizes the canonical pathway to activate NF-kappaB in an IKK2- and NEMO-, but not IKK1-, dependent manner. NF-kappaB DNA binding activity induced upon virus infection was shown to be composed of RelA:p50 dimers in these fibroblasts. Type I interferon (IFN) production was significantly decreased but not completely abolished upon virus infection in cells defective in NF-kappaB activation. In contrast, induction of classical MHC-I (class 1a) genes and their cell surface expression remained unaffected in these NF-kappaB-defective cells. However, MHC-I induction was impaired in IFNAR(-/-) cells that lack the alpha/beta IFN receptor, indicating a dominant role of type I IFNs but not NF-kappaB for the induction of MHC-I molecules by Japanese encephalitis virus. Our further analysis revealed that the residual type I IFN signaling in NF-kappaB-deficient cells is sufficient to drive MHC-I gene expression upon virus infection in mouse embryonic fibroblasts. However, NF-kappaB could indirectly regulate MHC-I expression, since JEV-induced type I IFN expression was found to be critically dependent on it. PMID- 20357097 TI - Autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys. AB - While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored env sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies. PMID- 20357098 TI - Identification of a domain of the baculovirus Autographa californica multiple nucleopolyhedrovirus single-strand DNA-binding protein LEF-3 essential for viral DNA replication. AB - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) lef-3 is one of nine genes required for viral DNA replication in transient assays. LEF-3 is predicted to contain several domains related to its functions, including nuclear localization, single-strand DNA binding, oligomerization, interaction with P143 helicase, and interaction with a viral alkaline nuclease. To investigate the essential nature of LEF-3 and the roles it may play during baculovirus DNA replication, a lef-3 null bacmid (bKO-lef3) was constructed in Escherichia coli and characterized in Sf21 cells. The results showed that AcMNPV lef-3 is essential for DNA replication, budded virus production, and late gene expression in vivo. Cells transfected with the lef-3 knockout bacmid produced low levels of early proteins (P143, DNA polymerase, and early GP64) and no late proteins (P47, VP39, or late GP64). To investigate the functional role of domains within the LEF 3 open reading frame in the presence of the whole viral genome, plasmids expressing various LEF-3 truncations were transfected into Sf21 cells together with bKO-lef3 DNA. The results showed that expression of AcMNPV LEF-3 amino acids 1 to 125 was sufficient to stimulate viral DNA replication and to support late gene expression. Expression of Choristoneura fumiferana MNPV lef-3 did not rescue any LEF-3 functions. The construction of a LEF-3 amino acid 1 to 125 rescue bacmid revealed that this region of LEF-3, when expressed in the presence of the rest of the viral genome, stimulated viral DNA replication and late and very late protein expression, as well as budded virus production. PMID- 20357100 TI - Conformational changes in the capsid of a calicivirus upon interaction with its functional receptor. AB - Nonenveloped viral capsids are metastable structures that undergo conformational changes during virus entry that lead to interactions of the capsid or capsid fragments with the cell membrane. For members of the Caliciviridae, neither the nature of these structural changes in the capsid nor the factor(s) responsible for inducing these changes is known. Feline junctional adhesion molecule A (fJAM A) mediates the attachment and infectious viral entry of feline calicivirus (FCV). Here, we show that the infectivity of some FCV isolates is neutralized following incubation with the soluble receptor at 37 degrees C. We used this property to select mutants resistant to preincubation with the soluble receptor. We isolated and sequenced 24 soluble receptor-resistant (srr) mutants and characterized the growth properties and receptor-binding activities of eight mutants. The location of the mutations within the capsid structure of FCV was mapped using a new 3.6-A structure of native FCV. The srr mutations mapped to the surface of the P2 domain were buried at the protruding domain dimer interface or were present in inaccessible regions of the capsid protein. Coupled with data showing that both the parental FCV and the srr mutants underwent increases in hydrophobicity upon incubation with the soluble receptor at 37 degrees C, these findings indicate that FCV likely undergoes conformational change upon interaction with its receptor. Changes in FCV capsid conformation following its interaction with fJAM-A may be important for subsequent interactions of the capsid with cellular membranes, membrane penetration, and genome delivery. PMID- 20357101 TI - Functional contribution of adult-generated olfactory bulb interneurons: odor discrimination versus odor memory. PMID- 20357099 TI - Murine coronavirus delays expression of a subset of interferon-stimulated genes. AB - The importance of the type I interferon (IFN-I) system in limiting coronavirus replication and dissemination has been unequivocally demonstrated by rapid lethality following infection of mice lacking the alpha/beta IFN (IFN-alpha/beta) receptor with mouse hepatitis virus (MHV), a murine coronavirus. Interestingly, MHV has a cell-type-dependent ability to resist the antiviral effects of IFN alpha/beta. In primary bone-marrow-derived macrophages and mouse embryonic fibroblasts, MHV replication was significantly reduced by the IFN-alpha/beta induced antiviral state, whereas IFN treatment of cell lines (L2 and 293T) has only minor effects on replication (K. M. Rose and S. R. Weiss, Viruses 1:689-712, 2009). Replication of other RNA viruses, including Theiler's murine encephalitis virus (TMEV), vesicular stomatitis virus (VSV), Sindbis virus, Newcastle disease virus (NDV), and Sendai virus (SeV), was significantly inhibited in L2 cells treated with IFN-alpha/beta, and MHV had the ability to rescue only SeV replication. We present evidence that MHV infection can delay interferon stimulated gene (ISG) induction mediated by both SeV and IFN-beta but only when MHV infection precedes SeV or IFN-beta exposure. Curiously, we observed no block in the well-defined IFN-beta signaling pathway that leads to STAT1-STAT2 phosphorylation and translocation to the nucleus in cultures infected with MHV. This observation suggests that MHV must inhibit an alternative IFN-induced pathway that is essential for early induction of ISGs. The ability of MHV to delay SeV-mediated ISG production may partially involve limiting the ability of IFN regulatory factor 3 (IRF-3) to function as a transcription factor. Transcription from an IRF-3-responsive promoter was partially inhibited by MHV; however, IRF-3 was transported to the nucleus and bound DNA in MHV-infected cells superinfected with SeV. PMID- 20357102 TI - Differential effects of ApoE isoforms on dendritic spines in vivo: linking an Alzheimer's disease risk factor with synaptic alterations. PMID- 20357103 TI - Molecular cross talk between misfolded proteins in animal models of Alzheimer's and prion diseases. AB - The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration and exacerbation of both pathologies. The onset of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. A striking increase in amyloid plaque deposition was observed in prion-infected mice compared with their noninoculated counterparts. Histological and biochemical studies showed the association of the two misfolded proteins in the brain and in vitro experiments showed that protein misfolding can be enhanced by a cross-seeding mechanism. These results suggest a profound interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second one. Our findings may have important implications to understand the origin and progression of PMDs. PMID- 20357105 TI - Early spatial attentional modulation of inputs to the fovea. AB - Attending to a specific spatial location modulates responsivity of neurons with receptive fields processing that part of the environment. A major outstanding question is whether attentional modulation operates differently for the foveal (central) representation of the visual field than it does for the periphery. Indeed, recent animal electrophysiological recordings suggest that attention differentially affects spatial integration for central and peripheral receptive fields in primary visual cortex. In human electroencephalographic recordings, spatial attention to peripheral locations robustly modulates activity in early visual regions, but it has been claimed that this mechanism does not operate in foveal vision. Here, however, we show clear early attentional modulation of foveal stimulation with the same timing and cortical sources as seen for peripheral stimuli, demonstrating that attentional gain control operates similarly across the entire field of view. These results imply that covertly attending away from the center of gaze, which is a common paradigm in behavioral and electrophysiological studies of attention, results in a precisely timed push pull mechanism. While the amplitude of the initial response to stimulation at attended peripheral locations is significantly increased beginning at 80 ms, the amplitude of the response to foveal stimulation begins to be attenuated. PMID- 20357104 TI - Different relationship of N- and P/Q-type Ca2+ channels to channel-interacting slots in controlling neurotransmission at cultured hippocampal synapses. AB - Synaptic transmission at CNS synapses is often mediated by joint actions of multiple Ca(2+) channel subtypes, most prominently, P/Q- and N-type. We have proposed that P/Q-type Ca(2+) channels saturate type-preferring slots at presynaptic terminals, which impose a ceiling on the synaptic efficacy of the channels. To test for analogous interactions for presynaptic N-type Ca(2+) channels, we overexpressed their pore-forming Ca(V)2.2 subunit in cultured mouse hippocampal neurons, recorded excitatory synaptic transmission from transfected cells, and dissected the contributions of N-, P/Q-, and R-type channels with subtype-specific blockers. Overexpression of Ca(V)2.2 did not increase the absolute size of the EPSC even though somatic N-type current was augmented by severalfold. Thus, the strength of neurotransmission is saturated with regard to levels of Ca(2+) channel expression for both N-type and P/Q-type channels. Overexpression of Ca(2+)-impermeable Ca(V)2.2 subunits decreased EPSC size, corroborating competition for channel slots. Striking asymmetries between N- and P/Q-type channels emerged when their relative contributions were compared with channel overexpression. Overexpressed N-type channels could competitively displace P/Q-type channels from P/Q-preferring slots and take over the role of supporting transmission. The converse was not found with overexpression of P/Q type channels, regardless of their C-terminal domain. We interpret these findings in terms of two different kinds of presynaptic slots at excitatory synapses, one accepting N-type channels but rejecting P/Q-type (N(specific)) and the other preferring P/Q-type but also accepting N-type (PQ(preferring)). The interaction between channels and slots governs the respective contributions of multiple channel types to neurotransmission and, in turn, the ability of transmission to respond to various stimulus patterns and neuromodulators. PMID- 20357106 TI - Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease. AB - Oxidative stress contributes to neurodegeneration in Huntington's disease (HD). However, the origins of oxidative stress in HD remain unclear. Studies in HD transgenic models suggest involvement of mitochondrial dysfunction, which would lead to overproduction of reactive oxygen species (ROS). Impaired mitochondria complexes occur in late stages of HD but not in presymptomatic or early-stage HD patients. Thus, other mechanisms may account for the earliest source of oxidative stress caused by endogenous mutant huntingtin. Here, we report that decreased levels of a major intracellular antioxidant glutathione coincide with accumulation of ROS in primary HD neurons prepared from embryos of HD knock-in mice (HD(140Q/140Q)), which have human huntingtin exon 1 with 140 CAG repeats inserted into the endogenous mouse huntingtin gene. Uptake of extracellular cysteine through the glutamate/cysteine transporter EAAC1 is required for de novo synthesis of glutathione in neurons. We found that, compared with wild-type neurons, HD neurons had lower cell surface levels of EAAC1 and were deficient in taking up cysteine. Constitutive trafficking of EAAC1 from recycling endosomes relies on Rab11 activity, which is defective in the brain of HD(140Q/140Q) mice. Enhancement of Rab11 activity by expression of a dominant-active Rab11 mutant in primary HD neurons ameliorated the deficit in cysteine uptake, increased levels of intracellular glutathione, normalized clearance of ROS, and improved neuronal survival. Our data support a novel mechanism for oxidative stress in HD: Rab11 dysfunction slows trafficking of EAAC1 to the cell surface and impairs cysteine uptake, thereby leading to deficient synthesis of glutathione. PMID- 20357107 TI - Role of G-proteins in odor-sensing and CO2-sensing neurons in Drosophila. AB - A central question in insect chemoreception is whether signaling occurs via G proteins. Two families of seven-transmembrane-domain chemoreceptors, the odor (Or) and gustatory receptor (Gr) families, have been identified in Drosophila (Clyne et al., 1999, 2000; Vosshall et al., 1999). Ors mediate odor responses, whereas two Grs, Gr21a and Gr63a, mediate CO2 response (Hallem et al., 2004; Jones et al., 2007; Kwon et al., 2007). Using single-sensillum recordings, we systematically investigate the role of Galpha proteins in vivo, initially with RNA interference constructs, competitive peptides, and constitutively active Galpha proteins. The results do not support a role for Galpha proteins in odor sensitivity. In parallel experiments, manipulations of Galpha(q), but not other Galpha proteins, affected CO2 response. Transient, conditional, and ectopic expression analyses consistently supported a role for Galpha(q) in the response of CO2-sensing neurons, but not odor-sensing neurons. Genetic mosaic analysis confirmed that odor responses are normal in the absence of Galpha(q). Ggamma30A is also required for normal CO2 response. The simplest interpretation of these results is that Galpha(q) and Ggamma30A play a role in the response of CO2 sensing neurons, but are not required for Or-mediated odor signaling. PMID- 20357108 TI - The angiogenic factor angiopoietin-1 is a proneurogenic peptide on subventricular zone stem/progenitor cells. AB - In the adult mammalian brain, the subventricular zone (SVZ) hosts stem cells constantly generating new neurons. Angiopoietin-1 (Ang-1) is an endothelial growth factor with a critical role in division, survival, and adhesion of endothelial cells via Tie-2 receptor activity. Expression of Tie-2 in nonendothelial cells, especially neurons and stem cells, suggests that Ang-1 may be involved in neurogenesis. In the present work, we investigated the putative role of Ang-1 on SVZ neurogenesis. Immature cells from SVZ-derived neurospheres express Ang-1 and Tie-2 mRNA, suggesting a role for the Ang-1/Tie-2 system in the neurogenic niche. Moreover, we also found that Tie-2 protein expression is retained on differentiation in neurons and glial cells. Ang-1 triggered proliferation via activation of the ERK1/2 (extracellular signal-regulated kinase 1/2) mitogen-activated protein kinase (MAPK) kinase pathway but did not induce cell death. Accordingly, coincubation with an anti-Tie-2 neutralizing antibody prevented the pro-proliferative effect of Ang-1. Furthermore, Ang-1 increased the number of NeuN (neuronal nuclear protein)-positive neurons in cultures treated for 7 d, as well as the number of functional neurons, as assessed by monitoring [Ca(2+)](i) rises after application of specific stimuli for neurons and immature cells. The proneurogenic effect of Ang-1 is mediated by Tie-2 activation and subsequent mTOR (mammalian target of rapamycin kinase) mobilization. In agreement, neuronal differentiation significantly decreased after exposure to an anti-Tie-2 neutralizing antibody and to rapamycin. Moreover, Ang-1 elicited the activation of the SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase) MAPK, involved in axonogenesis. Our work shows a proneurogenic effect of Ang-1, highlighting the relevance of blood vessel/stem cell cross talk in health and disease. PMID- 20357109 TI - The range of intrinsic frequencies represented by medial entorhinal cortex stellate cells extends with age. AB - In both humans and rodents, the external environment is encoded in the form of cognitive maps. Neurons in the medial entorhinal cortex (mEC) represent spatial locations in a sequence of grid-like patterns scaled along the dorsal-ventral axis. The grid spacing correlates with the intrinsic resonance frequencies of stellate cells in layer II of mEC. We investigated the development of frequency preferences in these cells from weaning to adulthood using patch-clamp and sharp microelectrode recordings. We found that the dorsal-ventral gradient of stellate cell properties and frequency preferences exists before animals are able to actively explore their environment. In the transition to adulthood, cells respond faster and become less excitable, and the range of intrinsic resonance frequencies in the population expands in the dorsal direction. This is likely to reflect both the growth of the brain and the expansion of the internal representation caused by new exploratory experience. PMID- 20357110 TI - Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning. AB - NMDA receptors (NMDARs) are key mediators of certain forms of synaptic plasticity and learning. NMDAR complexes are heteromers composed of an obligatory GluN1 subunit and one or more GluN2 (GluN2A-GluN2D) subunits. Different subunits confer distinct physiological and molecular properties to NMDARs, but their contribution to synaptic plasticity and learning in the adult brain remains uncertain. Here, we generated mice lacking GluN2B in pyramidal neurons of cortex and CA1 subregion of hippocampus. We found that hippocampal principal neurons of adult GluN2B mutants had faster decaying NMDAR-mediated EPSCs than nonmutant controls and were insensitive to GluN2B but not NMDAR antagonism. A subsaturating form of hippocampal long-term potentiation (LTP) was impaired in the mutants, whereas a saturating form of LTP was intact. An NMDAR-dependent form of long-term depression (LTD) produced by low-frequency stimulation combined with glutamate transporter inhibition was abolished in the mutants. Additionally, mutants exhibited decreased dendritic spine density in CA1 hippocampal neurons compared with controls. On multiple assays for corticohippocampal-mediated learning and memory (hidden platform Morris water maze, T-maze spontaneous alternation, and pavlovian trace fear conditioning), mutants were impaired. These data further demonstrate the importance of GluN2B for synaptic plasticity in the adult hippocampus and suggest a particularly critical role in LTD, at least the form studied here. The finding that loss of GluN2B was sufficient to cause learning deficits illustrates the contribution of GluN2B-mediated forms of plasticity to memory formation, with implications for elucidating NMDAR-related dysfunction in disease-related cognitive impairment. PMID- 20357111 TI - TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. AB - Thermosensitive TRP (thermo TRP) channels are well recognized for their contributions to sensory transduction, responding to a wide variety of stimuli including temperature, nociceptive stimuli, touch, and osmolarity. However, the precise roles for the thermo TRP channels during development have not been determined. To explore the functional importance of thermo TRP channels during neural development, the temporal expression was determined in embryonic mice. Interestingly, TRPV2 expression was detected in spinal motor neurons in addition to the dorsal root ganglia from embryonic day 10.5 and was localized in axon shafts and growth cones, suggesting that the channel is important for axon outgrowth regulation. We revealed that endogenous TRPV2 was activated in a membrane stretch-dependent manner in developing neurons by knocking down the TRPV2 function with dominant-negative TRPV2 and TRPV2-specific shRNA and significantly promoted axon outgrowth. Thus, for the first time we revealed that TRPV2 is an important regulator for axon outgrowth through its activation by membrane stretch during development. PMID- 20357113 TI - Accumbens shell-hypothalamus interactions mediate extinction of alcohol seeking. AB - The nucleus accumbens shell (AcbSh) is required to inhibit drug seeking after extinction training. Conversely, the lateral hypothalamus (LH), which receives projections from AcbSh, mediates reinstatement of previously extinguished drug seeking. We hypothesized that reversible inactivation of AcbSh using GABA agonists (baclofen/muscimol) would reinstate extinguished alcohol seeking and increase neuronal activation in LH. Rats underwent self-administration training for 4% (v/v) alcoholic beer followed by extinction. AcbSh inactivation reinstated extinguished alcohol seeking when infusions were made after, but not before, extinction training. We then used immunohistochemical detection of c-Fos as a marker of neuronal activity, combined with immunohistochemical detection of the orexin and cocaine- and amphetamine-related transcript (CART) peptides, to study the profile and phenotype of neural activation during reinstatement produced by AcbSh inactivation. AcbSh inactivation increased c-Fos expression in hypothalamus, as well as in paraventricular thalamus and amygdala. Within hypothalamus, there was an increase in the number of orexin and CART cells expressing c-Fos. Finally, we hypothesized that concurrent inactivation of LH would prevent reinstatement produced by inactivation of AcbSh alone. Our results confirmed this. Together, these findings suggest that AcbSh mediates extinction of reward seeking by inhibiting hypothalamic neuropeptide neurons. Reversible inactivation of the AcbSh removes this influence, thereby releasing hypothalamus from AcbSh inhibition and enabling reinstatement of reward seeking. These ventral striatal-hypothalamic circuits for extinction overlap with those that mediate satiety, and we suggest that extinction training inhibits drug seeking because it co-opts neural circuits originally selected to produce satiety. PMID- 20357112 TI - Attention-like modulation of hippocampus place cell discharge. AB - Hippocampus place cell discharge is an important model system for understanding cognition, but evidence is missing that the place code is under the kind of dynamic attentional control characterized in primates as selective activation of one neural representation and suppression of another, competing representation. We investigated the apparent noise ("overdispersion") in the CA1 place code, hypothesizing that overdispersion results from discharge fluctuations as spatial attention alternates between distal cues and local/self-motion cues. The hypothesis predicts that: (1) preferential use of distal cues will decrease overdispersion; (2) global, attention-like states can be decoded from ensemble discharge such that both the discharge rates and the spatial firing patterns of individual cells will be distinct in the two states; (3) identifying attention like states improves reconstructions of the rat's path from ensemble discharge. These predictions were confirmed, implying that a covert, dynamic attention-like process modulates discharge on a approximately 1 s time scale. We conclude the hippocampus place code is a dynamic representation of the spatial information in the immediate focus of attention. PMID- 20357114 TI - Reelin regulates postnatal neurogenesis and enhances spine hypertrophy and long term potentiation. AB - Reelin, an extracellular protein essential for neural migration and lamination, is also expressed in the adult brain. To unravel the function of this protein in the adult forebrain, we generated transgenic mice that overexpress Reelin under the control of the CaMKIIalpha promoter. Overexpression of Reelin increased adult neurogenesis and impaired the migration and positioning of adult-generated neurons. In the hippocampus, the overexpression of Reelin resulted in an increase in synaptic contacts and hypertrophy of dendritic spines. Induction of long-term potentiation (LTP) in alert-behaving mice showed that Reelin overexpression evokes a dramatic increase in LTP responses. Hippocampal field EPSP during a classical conditioning paradigm was also increased in these mice. Our results indicate that Reelin levels in the adult brain regulate neurogenesis and migration, as well as the structural and functional properties of synapses. These observations suggest that Reelin controls developmental processes that remain active in the adult brain. PMID- 20357115 TI - Voltage-gated Na channels in AII amacrine cells accelerate scotopic light responses mediated by the rod bipolar cell pathway. AB - During night (i.e., scotopic) vision in mammals, rod photoreceptor output is conveyed to ganglion cells (GCs), the output cells of the retina, by a specialized neural circuit comprising rod bipolar (RB) and AII amacrine cells. Here, we examined how intrinsic postsynaptic conductances in AIIs contribute to transmission of rod-derived signals. Using paired recordings from synaptically coupled RBs and AIIs, we found that a voltage-gated Na conductance in AII amacrines accelerated EPSPs arising from RB synaptic input. EPSPs also could be amplified by the Na conductance when AIIs were hyperpolarized below resting membrane potential, thereby increasing the availability of Na channels. AII amacrines are coupled electrically, and coupled AII amacrines likely receive common input from individual RBs. Na channel-mediated effects on EPSPs, however, appeared to occur at the single-cell rather than the AII network level. By recording light-evoked synaptic currents from GCs, we determined that the Na channel-dependent acceleration, but not amplification, of RB output by AII amacrines is reflected in the dynamics of AII synaptic output to retinal ganglion cells: synaptic inputs to both ON and OFF GCs are slowed equivalently, although not attenuated in amplitude, when Na channels in AIIs are blocked. Thus, during scotopic vision, Na conductances in AIIs serve to accelerate RB output. PMID- 20357116 TI - Shared mechanisms for opioid tolerance and a transition to chronic pain. AB - Clinical pain conditions may remain responsive to opiate analgesics for extended periods, but such persistent acute pain can undergo a transition to an opiate resistant chronic pain state that becomes a much more serious clinical problem. To test the hypothesis that cellular mechanisms of chronic pain in the primary afferent also contribute to the development of opiate resistance, we used a recently developed model of the transition of from acute to chronic pain, hyperalgesic priming. Repeated intradermal administration of the potent and highly selective mu-opioid agonist, [d-Ala(2),N-MePhe(4),gly-ol]-enkephalin (DAMGO), to produce tolerance for its inhibition of prostaglandin E(2) hyperalgesia, simultaneously produced hyperalgesic priming. Conversely, injection of an inflammogen, carrageenan, used to produce priming produced DAMGO tolerance. Both effects were prevented by inhibition of protein kinase Cepsilon (PKCepsilon). Carrageenan also induced opioid dependence, manifest as mu-opioid receptor antagonist (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2))-induced hyperalgesia that, like priming, was PKCepsilon and G(i) dependent. These findings suggest that the transition from acute to chronic pain, and development of mu-opioid receptor tolerance and dependence may be linked by common cellular mechanisms in the primary afferent. PMID- 20357117 TI - Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells. AB - Despite their therapeutic potential, progress in generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuraxis. GABAergic interneuron precursors have the remarkable ability to migrate extensively and survive after transplantation into postnatal cortex, making them an attractive candidate for use in cell-based therapy for seizures or other neuropsychiatric disorders. We have modified a mouse ESC line with an Lhx6-GFP reporter construct that allows for the isolation of newly generated cortical interneuron precursors. When transplanted into postnatal cortex, these cells can migrate into the cortical parenchyma, survive for months, and display morphological, neurochemical, and electrophysiological properties characteristic of mature interneurons. This work demonstrates that forebrain neuronal subtypes with complex traits can be generated from embryonic stem cells, and provides a novel approach to the study of cortical interneuron development and to the establishment of cell-based therapies for neurological disease. PMID- 20357118 TI - Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala. AB - Drug seeking and the vulnerability to relapse occur when individuals are exposed to an environment with sensory cues in which drug taking has occurred. Memory formation is thought to require plasticity in synaptic circuits, and so we examined whether the memory for a drug-paired environment correlates with changes in the synaptic circuits of the basolateral amygdala (BLA), in which emotional learning is a recognized phenomenon. We used amphetamine (AMPH) as the unconditioned stimulus in the conditioned place preference (CPP) paradigm. Rats were conditioned with 1.0 mg/kg AMPH and tested, drug free, 72 h after the last conditioning session. Controls included a saline-conditioned group and a home cage AMPH injection group, whose exposure to the CPP apparatus was delayed by 4 h, long enough to clear the AMPH from the brain. We counted excitatory synapses in the BLA using the electron microscope and the physical disector design (stereology). Rats that expressed AMPH CPP had an increase in excitatory synapses compared with controls. Excitatory synaptic activity was measured using in vivo intracellular recordings from the BLA in anesthetized rats. We found that AMPH CPP, but not drug alone, increased measures of synaptic drive, including the frequency of synaptic events, and the paired-pulse ratio of synaptic inputs to BLA pyramidal neurons. The in vivo findings suggest that the increase in BLA neuronal excitatory drive reflects the change in excitatory synapse number. Thus, context-drug associations are accompanied by structural and functional plasticity in the BLA, findings that have important implications for drug-seeking behavior. PMID- 20357119 TI - Slow and persistent postinhibitory rebound acts as an intrinsic short-term memory mechanism. AB - Many neurons exhibit postinhibitory rebound (PIR), in which neurons display enhanced excitability following inhibition. PIR can strongly influence the timing of spikes on rebound from an inhibitory input. We studied PIR in the lateral pyloric (LP) neuron of the stomatogastric ganglion of the crab Cancer borealis. The LP neuron is part of the pyloric network, a central pattern generator that normally oscillates with a period of approximately 1 s. We used the dynamic clamp to create artificial rhythmic synaptic inputs of various periods and duty cycles in the LP neuron. Surprisingly, we found that the strength of PIR increased slowly over multiple cycles of synaptic input. Moreover, this increased excitability persisted for 10-20 s after the rhythmic inhibition was removed. These effects are considerably slower than the rhythmic activity typically observed in LP. Thus this slow postinhibitory rebound allows the neuron to adjust its level of excitability to the average level of inhibition over many cycles, and is another example of an intrinsic "short-term memory" mechanism. PMID- 20357121 TI - Past experience modulates the neural mechanisms of episodic memory formation. AB - Neuroscientists have observed the "birth" of memories, but have not explored how an organism's past experience with materials interacts with the neural mechanisms of episodic memory formation. Using functional neuroimaging, we searched for such an interaction by examining brain activity during memory encoding that predicted participants' subsequent episodic memory for novel and repeated scenes. Memory for both scene types was predicted by a common posterior network in occipital and parietal cortices. Medial temporal memory predictors were modulated by scene repetition: the right anterior hippocampus and right amygdala predicted memory for novel scenes only, whereas posterior hippocampi predicted memory for repeated scenes only. There was also greater functional connectivity between the temporal pole and anterior versus posterior hippocampus, and this link predicted memory for novel but not repeated scenes. In contrast, there was greater functional connectivity between the precuneus and posterior versus anterior hippocampus, and this link predicted memory for repeated but not novel scenes. Together, these results reveal a functional specialization within the hippocampus for the encoding of novel and previously experienced materials, and suggest that the topography of this specialization might be related to local variations in connectivity. Because episodic memory for repeated scenes was superior, our results also support traditional views of encoding emphasizing the role of prior representations, and illuminate one way in which humans use existing memories to help form new ones. In so doing, our results challenge recent novelty-encoding hypotheses. PMID- 20357122 TI - Differential regulation of dopaminergic gene expression by Er81. AB - A recent study proposed that differentiation of dopaminergic neurons requires a conserved "dopamine motif" (DA-motif) that functions as a binding site for ETS DNA binding domain transcription factors. In the mammalian olfactory bulb (OB), the expression of a set of five genes [including tyrosine hydroxylase (Th)] that are necessary for differentiation of dopaminergic neurons was suggested to be regulated by the ETS-domain transcription factor ER81 via the DA-motif. To investigate this putative regulatory role of ER81, expression levels of these five genes were compared in both olfactory bulbs of adult wild-type mice subjected to unilateral naris closure and the olfactory bulbs of neonatal Er81 wild-type and mutant mice. These studies found that ER81 was necessary only for Th expression and not the other cassette genes. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA) experiments showed that ER81 bound directly to a consensus binding site/DA-motif in the rodent Th proximal promoter. However, the ER81 binding site/DA-motif in the Th proximal promoter is poorly conserved in other mammals. Both ChIP assays with canine OB tissue and EMSA experiments with the human Th proximal promoter did not detect ER81 binding to the Th DA-motif from these species. These results suggest that regulation of Th expression by the direct binding of ER81 to the Th promoter is a species-specific mechanism. These findings indicate that ER81 is not necessary for expression of the OB dopaminergic gene cassette and that the DA-motif is not involved in differentiation of the mammalian OB dopaminergic phenotype. PMID- 20357120 TI - A chemical screen identifies novel compounds that overcome glial-mediated inhibition of neuronal regeneration. AB - A major barrier to regeneration of CNS axons is the presence of growth-inhibitory proteins associated with myelin and the glial scar. To identify chemical compounds with the ability to overcome the inhibition of regeneration, we screened a novel triazine library, based on the ability of compounds to increase neurite outgrowth from cerebellar neurons on inhibitory myelin substrates. The screen produced four "hit compounds," which act with nanomolar potency on several different neuronal types and on several distinct substrates relevant to glial inhibition. Moreover, the compounds selectively overcome inhibition rather than promote growth in general. The compounds do not affect neuronal cAMP levels, PKC activity, or EGFR (epidermal growth factor receptor) activation. Interestingly, one of the compounds alters microtubule dynamics and increases microtubule density in both fibroblasts and neurons. This same compound promotes regeneration of dorsal column axons after acute lesions and potentiates regeneration of optic nerve axons after nerve crush in vivo. These compounds should provide insight into the mechanisms through which glial-derived inhibitors of regeneration act, and could lead to the development of novel therapies for CNS injury. PMID- 20357123 TI - Interleukin-15 receptor is essential to facilitate GABA transmission and hippocampal-dependent memory. AB - Interleukin-15 (IL15) is a cytokine produced by normal brain, but the functions of the IL15 system in normal adults are not yet clear. The hypothesis that the hippocampal IL15 system is essential for memory consolidation was tested by use of IL15Ralpha knock-out mice in behavioral, biochemical, immunohistological, and electron microscopic analyses. The knock-out mice showed deficits in memory, determined by the Stone T-maze and fear conditioning. In their hippocampi, the concentration of GABA was significantly lower. There were region-specific changes of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), with increased GAD-67-immunopositive interneurons in the stratum oriens of the CA1 region of the hippocampus, accompanied by nonsignificant reduction of GAD-67 synapses in the CA3 region. Western blotting showed an increase of GAD-65, but not GAD-67, in the hippocampal homogenate. The ultrastructure of the hippocampus remained intact in the knock-out mice. To further test the hypothesis that IL15 directly modulates GABA turnover by reuptake mechanisms, the dose-response relationship of IL15 on (3)H-GABA uptake was determined in two neuronal cell lines. The effective and nontoxic dose was further used in the synaptosomal uptake studies. IL15 decreased the uptake of (3)H-GABA in synaptosomes from the forebrain of wild-type mice. Consistent with this, IL15Ralpha knock-out mice had increased synaptosomal uptake of (3)H-GABA. Overall, the results show novel functions of a unique cytokine in normal hippocampal activity by regulating GABA transmission. PMID- 20357124 TI - Synaptic mechanism for functional synergism between delta- and mu-opioid receptors. AB - By sustained activation of mu-opioid receptors (MORs), chronic opioids cause analgesic tolerance, physical dependence, and opioid addiction, common clinical problems for which an effective treatment is still lacking. Chronic opioids recruit delta-opioid receptors (DORs) to plasma membrane through exocytotic trafficking, but the role of this new DOR and its interaction with existing MOR in brain functions and in these clinical problems remain largely unknown. In this study, we investigated the mechanisms underlying synaptic and behavioral actions of chronic morphine-induced DORs and their interaction with MORs in nucleus raphe magnus (NRM) neurons important for opioid analgesia. We found that the emerged DOR inhibited GABAergic IPSCs through both the phospholipase A(2) (PLA(2)) and cAMP/protein kinase A (PKA) signaling pathways. MOR inhibition of IPSCs, normally mediated predominantly by the PLA(2) pathway, was additionally mediated by the cAMP/PKA pathway, with MOR potency significantly increased after chronic morphine treatment. Isobologram analysis revealed a synergistic DOR-MOR interaction in their IPSC inhibition, which was dependent on upregulated activities of both the PLA(2) and cAMP/PKA pathways. Furthermore, DOR and MOR agonists microinjected into the NRM in vivo also produced a PLA(2)-dependent synergism in their antinociceptive effects. These findings suggest that the cAMP/PKA pathway, upregulated by chronic opioids, becomes more important in the mechanisms of both MOR and DOR inhibition of GABA synaptic transmission after chronic opioid exposure, and DORs and MORs are synergic both synaptically and behaviorally in producing analgesic effects in a PLA(2)-dependent fashion, supporting the potential therapeutic use of DOR agonists in pain management under chronic opioid conditions. PMID- 20357125 TI - A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding. AB - Nucleus accumbens (NAc) inactivation increases food intake, indicating that NAc neurons exert ongoing inhibition of feeding. We previously described a subpopulation of NAc neurons that pause during sucrose licking and proposed that the pause permits consumption. We tested this hypothesis by first recording NAc neurons during sucrose consumption, and then electrically stimulating through the same electrodes. A large proportion of NAc shell and core neurons were inhibited during sucrose consumption, and local electrical stimulation abruptly interrupted licking. Effective stimulation sites were more anterior than ineffective sites in NAc. At low stimulus intensities, licking resumed immediately on stimulation offset. The latency to lick resumption from NAc neuron inhibition onset ( approximately 460 ms) was very similar to that after electrical stimulation offset ( approximately 440 ms). These results directly support the hypothesis that a significant subpopulation of NAc neurons inhibit palatable food consumption and that a pause in their firing is required to initiate and maintain consumption. PMID- 20357126 TI - SAP102 is a highly mobile MAGUK in spines. AB - Membrane-associated guanylate kinases (MAGUKs), which are essential proteins in the postsynaptic density (PSD), cluster and anchor glutamate receptors and other proteins at synapses. The MAGUK family includes PSD-95, PSD-93, SAP102, and SAP97. Individual family members can compensate for one another in their ability to recruit and retain receptors at the postsynaptic membrane as shown through deletion and knock-down studies. SAP102 is highly expressed in both young and mature neurons; however, little is known about its localization and mobility at synapses. Here, we compared the distribution, mobility, and turnover times of SAP102 to the well studied MAGUK PSD-95. Using light and electron microscopy, we found that SAP102 shows a broader distribution as well as peak localization further away from the postsynaptic membrane than PSD-95. Using fluorescence recovery after photobleaching (FRAP), we found that 80% of SAP102 and 36% of PSD 95 are mobile in spines. Previous studies showed that PSD-95 was stabilized at the PSD by N-terminal palmitoylation. We found that stabilization of SAP102 at the PSD was dependent on its SH3/GK domains but not its PDZ interactions. Furthermore, we showed that stabilizing actin or blocking NMDA/AMPA receptors reduced the mobile pool of SAP102 but did not affect the mobile pool of PSD-95. Our results show significant differences in the localization, binding mechanism, and mobility of SAP102 and PSD-95. These differences and the compensatory properties of the MAGUKs point out an unrecognized versatility of the MAGUKs in their function in synaptic organization and plasticity. PMID- 20357128 TI - ClC-2 voltage-gated channels constitute part of the background conductance and assist chloride extrusion. AB - The function of voltage-gated chloride channels in neurons is essentially unknown. The voltage-gated chloride channel ClC-2 mediates a chloride current in pyramidal cells of the hippocampus. We directly show that ClC-2 assists chloride extrusion after high chloride load. Furthermore, the loss of this chloride channel leads to a dramatic increase of the input resistance of CA1 pyramidal cells, making these cells more excitable. Surprisingly, basal synaptic transmission, as judged from recordings of field EPSPs, was decreased. This difference was eliminated when GABAergic inhibition was blocked. Recordings from hippocampal interneurons revealed ClC-2-mediated currents in a subset of these cells. An observed increase in GABAergic inhibition could thus be explained by an increase in the excitability of interneurons, caused by the loss of ClC-2. Together, we suggest a dual role for ClC-2 in neurons, providing an additional efflux pathway for chloride and constituting a substantial part of the background conductance, which regulates excitability. In ClC-2 knock-out mice, an increased inhibition seemingly balances the hyperexcitability of the network and thereby prevents epilepsy. PMID- 20357127 TI - Functional significance of striatal responses during episodic decisions: recovery or goal attainment? AB - Memory retrieval is typically a goal-directed behavior, and as such, potentially influenced by reinforcement and motivation processes. Although striatal activation is often evident during memory retrieval, its functional significance remains unclear because typical memory paradigms do not control the motivational significance of memory decisions. We used event-related functional magnetic resonance imaging (fMRI) to investigate striatal activation during recognition with and without performance-linked monetary incentives. During initial performance in the absence of incentives, dorsal striatal activation for "Old" memory conclusions nonetheless exceeded that for "New" conclusions regardless of the accuracy of these conclusions. In contrast, subsequent scans paired incentives with either "Old" or "New" conclusions and demonstrated greater activation for whichever judgment was potentially rewarded, both with and without performance feedback. The data demonstrate that striatal activation during recognition judgments does not signal monetary reward receipt, cognitive feedback, or successful episodic retrieval. Instead, it is heavily dependent upon satisfaction of the subjective goals of the observer. PMID- 20357129 TI - Superposition model predicts EEG occipital activity during free viewing of natural scenes. AB - Visual event-related potentials (ERPs) produced by a stimulus are thought to reflect either an increase of synchronized activity or a phase realignment of ongoing oscillatory activity, with both mechanisms sharing the assumption that ERPs are independent of the current state of the brain at the time of stimulation. In natural viewing, however, visual inputs occur one after another at specific subject-paced intervals through unconstrained eye movements. We conjecture that during natural viewing, ERPs generated after each fixation are better explained by a superposition of ongoing oscillatory activity related to the processing of previous fixations, with new activity elicited by the visual input at the current fixation. We examined the electroencephalography (EEG) signals that occur in humans at the onset of each visual fixation, both while subjects freely viewed natural scenes and while they viewed a black or gray background. We found that the fixation ERPs show visual components that are absent when subjects move their eyes on a homogeneous gray or black screen. Single-trial EEG signals that comprise the ERP are predicted more accurately by a model of superposition than by either phase resetting or the addition of evoked responses and stimulus-independent noise. The superposition of ongoing oscillatory activity and the visually evoked response results in a modification of the ongoing oscillation phase. The results presented suggest that the observed EEG signals reflect changes occurring in a common neuronal substrate rather than a simple summation at the scalp of signals from independent sources. PMID- 20357131 TI - Epigenetic gene silencing underlies C-fiber dysfunctions in neuropathic pain. AB - Peripheral nerve injury causes neuropathic pain, which is characterized by the paradoxical sensations of positive and negative symptoms. Clinically, negative signs are frequently observed; however, their underlying molecular mechanisms are largely unknown. Dysfunction of C-fibers is assumed to underlie negative symptoms and is accompanied by long-lasting downregulation of Na(v)1.8 sodium channel and mu-opioid receptor (MOP) in the dorsal root ganglion (DRG). In the present study, we found that nerve injury upregulates neuron-restrictive silencer factor (NRSF) expression in the DRG neurons mediated through epigenetic mechanisms. In addition, chromatin immunoprecipitation analysis revealed that nerve injury promotes NRSF binding to the neuron-restrictive silencer element within MOP and Na(v)1.8 genes, thereby causing epigenetic silencing. Furthermore, NRSF knockdown significantly blocked nerve injury-induced downregulations of MOP and Na(v)1.8 gene expressions, C-fiber hypoesthesia, and the losses of peripheral morphine analgesia and Na(v)1.8-selective blocker-induced hypoesthesia. Together, these data suggest that NRSF causes pathological and pharmacological dysfunction of C fibers, which underlies the negative symptoms in neuropathic pain. PMID- 20357132 TI - Mismatched decoding in the brain. AB - "How is information decoded in the brain?" is one of the most difficult and important questions in neuroscience. We have developed a general framework for investigating to what extent the decoding process in the brain can be simplified. First, we hierarchically constructed simplified probabilistic models of neural responses that ignore more than Kth-order correlations using the maximum entropy principle. We then computed how much information is lost when information is decoded using these simplified probabilistic models (i.e., "mismatched decoders"). To evaluate the information obtained by mismatched decoders, we introduced an information theoretic quantity, I*, which was derived by extending the mutual information in terms of communication rate across a channel. We showed that I* provides consistent results with the minimum mean-square error as well as the mutual information, and demonstrated that a previously proposed measure quantifying the importance of correlations in decoding substantially deviates from I* when many cells are analyzed. We then applied this proposed framework to spike data for vertebrate retina using short natural scene movies of 100 ms duration as a set of stimuli and computing the information contained in neural activities. Although significant correlations were observed in population activities of ganglion cells, information loss was negligibly small even if all orders of correlation were ignored in decoding. We also found that, if we inappropriately assumed stationarity for long durations in the information analysis of dynamically changing stimuli, such as natural scene movies, correlations appear to carry a large proportion of total information regardless of their actual importance. PMID- 20357130 TI - NOS1AP associates with Scribble and regulates dendritic spine development. AB - The formation and function of the neuronal synapse is dependent on the asymmetric distribution of proteins both presynaptically and postsynaptically. Recently, proteins important in establishing cellular polarity have been implicated in the synapse. We therefore performed a proteomic screen with known polarity proteins and identified novel complexes involved in synaptic function. Specifically, we show that the tumor suppressor protein, Scribble, associates with neuronal nitric oxide synthase (nNOS) adaptor protein (NOS1AP) [also known as C-terminal PDZ ligand of nNOS (CAPON)] and is found both presynaptically and postsynaptically. The Scribble-NOS1AP association is direct and is mediated through the phosphotyrosine-binding (PTB) domain of NOS1AP and the fourth PDZ domain of Scribble. Further, we show that Scribble bridges NOS1AP to a beta-Pix [beta-p21 activated kinase (PAK)-interacting exchange factor]/Git1 (G-protein-coupled receptor kinase-interacting protein)/PAK complex. The overexpression of NOS1AP leads to an increase in dendritic protrusions, in a fashion that depends on the NOS1AP PTB domain. Consistent with these observations, both full-length NOS1AP and the NOS1AP PTB domain influence Rac activity. Together these data suggest that NOS1AP plays an important role in the mammalian synapse. PMID- 20357133 TI - The PANSS should be rescaled. PMID- 20357134 TI - Schizophrenia in the internalizing-externalizing framework: a third dimension? AB - BACKGROUND: Prior studies of common disorders in community-dwelling adults identified internalizing and externalizing spectra of mental illness. We investigated the placement of schizophrenia and schizotypal personality disorder in this framework and tested the validity of the resulting organization in a clinical population. METHODS: The data came from the Suffolk County Mental Health Project cohort (N = 628), which consists of first-admission patients with psychosis recruited from inpatient units throughout Suffolk County, NY (72% response rate). The sample was reassessed multiple times over the following 10 years. Complete diagnostic data were available for 469 participants. Mental health professionals diagnosed 11 target conditions based on semistructured clinical interviews, review of medical records, and reports of significant others. Two validators were included: family history of schizophrenia and 10-year illness course. RESULTS: Confirmatory factor analysis revealed that the The Diagnostic and Statistical Manual of Mental Disorders-IV grouping of conditions fit the data poorly. The best alternative classification consisted of three clusters: internalizing, externalizing, and schizophrenic. Both validators supported the coherence and distinctiveness of the schizophrenic cluster. CONCLUSIONS: We replicated internalizing and externalizing spectra in a clinical population, identified a schizophrenic spectrum, and provided initial evidence of its validity. These findings suggest that schizotypal personality disorder may be better placed with schizophrenia, antisocial conditions with substance use disorders, and major depression with anxiety disorders. PMID- 20357135 TI - Role of thylakoid ATP/ADP carrier in photoinhibition and photoprotection of photosystem II in Arabidopsis. AB - The chloroplast thylakoid ATP/ADP carrier (TAAC) belongs to the mitochondrial carrier superfamily and supplies the thylakoid lumen with stromal ATP in exchange for ADP. Here, we investigate the physiological consequences of TAAC depletion in Arabidopsis (Arabidopsis thaliana). We show that the deficiency of TAAC in two T DNA insertion lines does not modify the chloroplast ultrastructure, the relative amounts of photosynthetic proteins, the pigment composition, and the photosynthetic activity. Under growth light conditions, the mutants initially displayed similar shoot weight, but lower when reaching full development, and were less tolerant to high light conditions in comparison with the wild type. These observations prompted us to study in more detail the effects of TAAC depletion on photoinhibition and photoprotection of the photosystem II (PSII) complex. The steady-state phosphorylation levels of PSII proteins were not affected, but the degradation of the reaction center II D1 protein was blocked, and decreased amounts of CP43-less PSII monomers were detected in the mutants. Besides this, the mutant leaves displayed a transiently higher nonphotochemical quenching of chlorophyll fluorescence than the wild-type leaves, especially at low light. This may be attributed to the accumulation in the absence of TAAC of a higher electrochemical H(+) gradient in the first minutes of illumination, which more efficiently activates photoprotective xanthophyll cycle-dependent and independent mechanisms. Based on these results, we propose that TAAC plays a critical role in the disassembly steps during PSII repair and in addition may balance the trans-thylakoid electrochemical H(+) gradient storage. PMID- 20357137 TI - Agrobacterium tumefaciens-mediated transformation of maize endosperm as a tool to study endosperm cell biology. AB - Developing maize (Zea mays) endosperms can be excised from the maternal tissues and undergo tissue/cell-type differentiation under in vitro conditions. We have developed a method to transform in vitro-grown endosperms using Agrobacterium tumefaciens and standard binary vectors. We show that both aleurone and starchy endosperm cells can be successfully transformed using a short cocultivation with A. tumefaciens cells. The highest transformation rates were obtained with the A. tumefaciens EHA101 strain and the pTF101.1 binary vector. The percentage of aleurone cells transformed following this method varied between 10% and 22% whereas up to the eighth layer of starchy endosperm cells underneath the aleurone layer showed transformed cells. Cultured endosperms undergo normal cell type (aleurone and starchy endosperm) differentiation and storage protein accumulation, making them suitable for cell biology and biochemical studies. In addition, transgenic cultured endosperms are able to express and accumulate epitope-tagged storage proteins that can be isolated for biochemical assays or used for immunolabeling techniques. PMID- 20357136 TI - Arabidopsis RAP2.2: an ethylene response transcription factor that is important for hypoxia survival. AB - Arabidopsis (Arabidopsis thaliana) RAP2.2 (At3g14230) is an APETALA2/ethylene response factor-type transcription factor that belongs to the same subfamily as the rice (Oryza sativa) submergence tolerance gene SUB1A. RAP2.2 is expressed at constitutively high levels in the roots and at lower levels in the shoots, where it is induced by darkness. Effector studies and analysis of ethylene signal transduction mutants indicate that RAP2.2 is induced in shoots by ethylene and functions in an ethylene-controlled signal transduction pathway. Overexpression of RAP2.2 resulted in improved plant survival under hypoxia (low-oxygen) stress, whereas lines containing T-DNA knockouts of the gene had poorer survival rates than the wild type. This indicates that RAP2.2 is important in a plant's ability to resist hypoxia stress. Observation of the expression pattern of 32 low-oxygen and ethylene-associated genes showed that RAP2.2 affects only part of the low oxygen response, particularly the induction of genes encoding sugar metabolism and fermentation pathway enzymes, as well as ethylene biosynthesis genes. Our results provide a new insight on the regulation of gene expression under low oxygen conditions. Lighting plays an important regulatory role and is intertwined with hypoxia conditions; both stimuli may act collaboratively to regulate the hypoxic response. PMID- 20357138 TI - Potential role for purple acid phosphatase in the dephosphorylation of wall proteins in tobacco cells. AB - It is not yet known whether dephosphorylation of proteins catalyzed by phosphatases occurs in the apoplastic space. In this study, we found that tobacco (Nicotiana tabacum) purple acid phosphatase could dephosphorylate the phosphoryl residues of three apoplastic proteins, two of which were identified as alpha xylosidase and beta-glucosidase. The dephosphorylation and phosphorylation of recombinant alpha-xylosidase resulted in a decrease and an increase in its activity, respectively, when xyloglucan heptasaccharide was used as a substrate. Attempted overexpression of the tobacco purple acid phosphatase NtPAP12 in tobacco cells not only decreased the activity levels of the glycosidases but also increased levels of xyloglucan oligosaccharides and cello-oligosaccharides in the apoplast during the exponential phase. We suggest that purple acid phosphatase controls the activity of alpha-xylosidase and beta-glucosidase, which are responsible for the degradation of xyloglucan oligosaccharides and cello oligosaccharides in the cell walls. PMID- 20357139 TI - Ectopic expression of apple F3'H genes contributes to anthocyanin accumulation in the Arabidopsis tt7 mutant grown under nitrogen stress. AB - Three genes encoding flavonoid 3'-hydroxylase (F3'H) in apple (Malus x domestica), designated MdF3'HI, MdF3'HIIa, and MdF3'HIIb, have been identified. MdF3'HIIa and MdF3'HIIb are almost identical in amino acid sequences, and they are allelic, whereas MdF3'HI has 91% nucleotide sequence identity in the coding region to both MdF3'HIIa and MdF3'HIIb. MdF3'HI and MdF3'HII genes are mapped onto linkage groups 14 and 6, respectively, of the apple genome. Throughout the development of apple fruit, transcriptional levels of MdF3'H genes along with other anthocyanin biosynthesis genes are higher in the red-skinned cv Red Delicious than that in the yellow-skinned cv Golden Delicious. Moreover, patterns of MdF3'H gene expression correspond to accumulation patterns of flavonoids in apple fruit. These findings suggest that MdF3'H genes are coordinately expressed with other genes in the anthocyanin biosynthetic pathway in apple. The functionality of these apple F3'H genes has been demonstrated via their ectopic expression in both the Arabidopsis (Arabidopsis thaliana) transparent testa7-1 (tt7) mutant and tobacco (Nicotiana tabacum). When grown under nitrogen-deficient conditions, transgenic Arabidopsis tt7 seedlings expressing apple F3'H regained red color pigmentation and significantly accumulated both 4'-hydrylated pelargonidin and 3',4'-hydrylated cyanidin. When compared with wild-type plants, flowers of transgenic tobacco lines overexpressing apple F3'H genes exhibited enhanced red color pigmentation. This suggests that the F3'H enzyme may coordinately interact with other flavonoid enzymes in the anthocyanin biosynthesis pathway. PMID- 20357141 TI - How sweet it is . . . (or isn't)! PMID- 20357140 TI - Regulation of microbe-associated molecular pattern-induced hypersensitive cell death, phytoalexin production, and defense gene expression by calcineurin B-like protein-interacting protein kinases, OsCIPK14/15, in rice cultured cells. AB - Although cytosolic free Ca(2+) mobilization induced by microbe/pathogen associated molecular patterns is postulated to play a pivotal role in innate immunity in plants, the molecular links between Ca(2+) and downstream defense responses still remain largely unknown. Calcineurin B-like proteins (CBLs) act as Ca(2+) sensors to activate specific protein kinases, CBL-interacting protein kinases (CIPKs). We here identified two CIPKs, OsCIPK14 and OsCIPK15, rapidly induced by microbe-associated molecular patterns, including chitooligosaccharides and xylanase (Trichoderma viride/ethylene-inducing xylanase [TvX/EIX]), in rice (Oryza sativa). Although they are located on different chromosomes, they have over 95% nucleotide sequence identity, including the surrounding genomic region, suggesting that they are duplicated genes. OsCIPK14/15 interacted with several OsCBLs through the FISL/NAF motif in yeast cells and showed the strongest interaction with OsCBL4. The recombinant OsCIPK14/15 proteins showed Mn(2+) dependent protein kinase activity, which was enhanced both by deletion of their FISL/NAF motifs and by combination with OsCBL4. OsCIPK14/15-RNAi transgenic cell lines showed reduced sensitivity to TvX/EIX for the induction of a wide range of defense responses, including hypersensitive cell death, mitochondrial dysfunction, phytoalexin biosynthesis, and pathogenesis-related gene expression. On the other hand, TvX/EIX-induced cell death was enhanced in OsCIPK15 overexpressing lines. Our results suggest that OsCIPK14/15 play a crucial role in the microbe-associated molecular pattern-induced defense signaling pathway in rice cultured cells. PMID- 20357142 TI - Context-sensitive airway management. PMID- 20357143 TI - In normal controls, both age and gender affect coagulability as measured by thrombelastography. AB - BACKGROUND: Our objective was to analyze the effects of age, gender, and the use of oral contraceptives (OCs) on coagulation using thrombelastography (TEG), a single test to analyze both plasma coagulation factors and cellular elements in whole blood. METHODS: TEG variables were measured in native whole blood and in recalcified citrated blood from 120 healthy adults (60 men and 60 women) with various ages and in an additional 29 healthy women using OCs. RESULTS: We observed hypercoagulability in women compared with men and in women using OCs compared with age-matched nonusers. Moreover, we found hypercoagulability with aging. Using the method of Bland and Altman (Lancet 1986;1:307-10), we demonstrated no correlation between TEG measurements in native and recalcified citrated blood. CONCLUSIONS: Aging, female gender, use of OCs, and low-normal hematocrit levels have significant procoagulant effects. TEG measurements in native and recalcified citrated blood are not interchangeable, as indicated by differences between the 2 measurements ranging from 20% in maximal amplitude to 246% in clotting time. Furthermore, the limits of agreement strongly exceeded clinical acceptability to conclude interchangeability. PMID- 20357144 TI - Derivation and validation of a simple perioperative sleep apnea prediction score. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a largely underdiagnosed, common condition, which is important to diagnose preoperatively because it has implications for perioperative management. Our purpose in this study was to identify independent clinical predictors of a diagnosis of OSA in a general surgical population, develop a perioperative sleep apnea prediction (P-SAP) score based on these variables, and validate the P-SAP score against standard overnight polysomnography. METHODS: A retrospective, observational study was designed to identify patients with a known diagnosis of OSA. Independent predictors of a diagnosis of OSA were derived by logistic regression, based on which prediction tool (P-SAP score) was developed. The P-SAP score was then validated in patients undergoing overnight polysomnography. RESULTS: The P-SAP score was derived from 43,576 adult cases undergoing anesthesia. Of these, 3884 patients (7.17%) had a documented diagnosis of OSA. Three demographic variables: age > 43 years, male gender, and obesity; 3 history variables: history of snoring, diabetes mellitus Type 2, and hypertension; and 3 airway measures: thick neck, modified Mallampati class 3 or 4, and reduced thyromental distance were identified as independent predictors of a diagnosis of OSA. A diagnostic threshold P-SAP score > or = 2 showed excellent sensitivity (0.939) but poor specificity (0.323), whereas for a P-SAP score > or = 6, sensitivity was poor (0.239) with excellent specificity (0.911). Validation of this P-SAP score was performed in 512 patients with similar accuracy. CONCLUSION: The P-SAP score predicts diagnosis of OSA with dependable accuracy across mild to severe disease. The elements of the P-SAP score are derived from a typical university hospital surgical population. PMID- 20357145 TI - High-dose bupivacaine remotely loaded into multivesicular liposomes demonstrates slow drug release without systemic toxic plasma concentrations after subcutaneous administration in humans. AB - BACKGROUND: Depot formulations prolong the analgesic effect of local anesthetics and reduce peak plasma drug concentration. This allows for safer administration of larger doses of local anesthetics, which further prolongs the duration of analgesic effect. We previously reported the development of large multivesicular vesicles (LMVVs) remotely loaded with bupivacaine (LMVV liposomal bupivacaine) and demonstrated a >5-fold prolongation of analgesic effect in animals and humans. In this study, we present pharmacokinetic data of LMVV liposomal bupivacaine in humans. METHODS: Healthy volunteers received subcutaneous injections of 20 mL plain 0.5% bupivacaine and, 1 week later, 20 mL of 2% LMVV liposomal bupivacaine in a prospective, open-label, crossover, controlled study. RESULTS: Eight subjects were studied. No subjective side effects of local anesthetics were observed. The maximal plasma concentration and the time to achieve maximal plasma concentration were assessed by modeling plasma concentration-time profiles. Maximal plasma concentration was not significantly different between groups (0.87 +/- 0.45 microg/mL and 0.83 +/- 0.34 microg/mL for plain and liposomal bupivacaine, respectively; P = not significant, 0.83). These values are well below the putative toxic plasma concentration of 2 to 4 microg/mL. Time to achieve maximal plasma concentration was 7-fold greater for the liposomal preparation (262 +/- 149 minutes vs 37.5 +/- 16 minutes, P < 0.01). CONCLUSIONS: Peak plasma bupivacaine concentrations were not different in the 2 groups, despite a 4-fold increase in total bupivacaine dose administered in the novel liposomal preparation. The delayed elimination and prolonged redistribution of liposomal bupivacaine to plasma is compatible with the depot-related slow release effect leading to the prolonged pharmacodynamic effect previously reported. PMID- 20357146 TI - Reversible conduction block in isolated toad sciatic nerve by emulsified isoflurane. AB - BACKGROUND: Studies have shown that the local use of volatile anesthetics can produce local anesthetic effects. We designed this study to evaluate the characteristics of nerve conduction block of emulsified isoflurane (EI) and compare its nerve blockade with 1%lidocaine, by measuring compound nerve action potential (CNAP) parameters in isolated toad sciatic nerve. METHODS: One hundred isolated toad sciatic nerves were selected and randomly assigned to 10 groups of 10 each, administered 2% to 8% EI (v/v) (EI(8) group, etc.), 1% lidocaine, 30% Intralipid(R) (Huarui Pharmacy, Wuxi, Jiangsu, China), and Ringer solution (RS) for 10 minutes, respectively. All nerves were then washed and soaked with RS for 10 minutes and 30 minutes. The nerve conduction block effect was represented by CNAP parameters that were recorded by an extracellular recording technique per minute. RESULTS: The results showed that the negative amplitudes of CNAP were decreased by EI and lidocaine (P < 0.05), and the conduction velocities of CNAP were also decreased at some time points (D7-W3) (P < 0.05). After RS washing, the 2 parameters recovered gradually. The changes in the 2 parameters induced by EI had slower onset rates and faster recoveries than those produced by lidocaine (7 minutes vs 1 minute and 9 minutes vs 30 minutes). The nerve blockade induced by EI was dose dependent (P < 0.05), and the half maximal inhibition concentration of EI was 5.46%. CONCLUSIONS: EI produced completely reversible and dose dependent nerve conduction inhibition, which had slower onset and faster recovery compared with those produced by lidocaine. PMID- 20357148 TI - A nasal catheter for the measurement of end-tidal carbon dioxide in spontaneously breathing patients: a preliminary evaluation. AB - BACKGROUND: Several devices have been proposed to monitor end-tidal carbon dioxide tension (Petco(2)) in spontaneously breathing patients; however, many have been reported to be inaccurate. We designed this study to investigate the accuracy of a balloon-tipped nasal catheter in measuring Petco(2) in nontracheally intubated, spontaneously breathing patients. METHODS: The catheter was assembled using a 14-F rubber Foley catheter, a tracheal tube pilot balloon, and the plastic sheath from an 18-gauge needle. The catheter was connected to the sampling tube of a gas analyzer. Petco(2) and Paco(2) were determined simultaneously in 20 otherwise healthy postsurgical patients while receiving oxygen. RESULTS: The mean Petco(2) - Paco(2) difference was -4.4 +/- 1.6 (SD) mm Hg with a correlation coefficient r = +0.87 (P < 0.001). CONCLUSION: Our results suggest that a balloon-tipped nasal catheter can provide a simple, easy, and reliable method for Petco(2) measurement in nontracheally intubated, spontaneously breathing patients. PMID- 20357147 TI - Monitoring with head-mounted displays in general anesthesia: a clinical evaluation in the operating room. AB - BACKGROUND: Patient monitors in the operating room are often positioned where it is difficult for the anesthesiologist to see them when performing procedures. Head-mounted displays (HMDs) can help anesthesiologists by superimposing a display of the patient's vital signs over the anesthesiologist's field of view. Simulator studies indicate that by using an HMD, anesthesiologists can spend more time looking at the patient and less at the monitors. We performed a clinical evaluation testing whether this finding would apply in practice. METHODS: Six attending anesthesiologists provided anesthesia to patients undergoing rigid cystoscopy. Each anesthesiologist performed 6 cases alternating between standard monitoring using a Philips IntelliVue MP70 and standard monitoring plus a Microvision Nomad ND2000 HMD. The HMD interfaced wirelessly with the MP70 monitor and displayed waveform and numerical vital signs data. Video was recorded during all cases and analyzed to determine the percentage of time, frequency, and duration of looks at the anesthesia workstation and at the patient and surgical field during various anesthetic phases. Differences between the display conditions were tested for significance using repeated-measures analysis of variance. RESULTS: Video data were collected from 36 cases that ranged from 17 to 75 minutes in duration (median 31 minutes). When participants were using the HMD, compared with standard monitoring, they spent less time looking toward the anesthesia workstation (21.0% vs 25.3%, P = 0.003) and more time looking toward the patient and surgical field (55.9% vs 51.5%, P = 0.014). The HMD had no effect on either the frequency of looks or the average duration of looks toward the patient and surgical field or toward the anesthesia workstation. CONCLUSIONS: An HMD of patient vital signs reduces anesthesiologists' surveillance of the anesthesia workstation and allows them to spend more time monitoring their patient and surgical field during normal anesthesia. More research is needed to determine whether the behavioral changes can lead to improved anesthesiologist performance in the operating room. PMID- 20357149 TI - Tracheal intubation of a difficult airway using Airway Scope, Airtraq, and Macintosh laryngoscope: a comparative manikin study of inexperienced personnel. AB - BACKGROUND: The Airway Scope (AWS) (Pentax-AWS, Hoya Corp., Tokyo, Japan) and the Airtraq (ATQ) (Prodol, Vizcaya, Spain) have similarities in the novel structures of their blades. In this study, we evaluated the ease of use of the AWS and ATQ compared with the Macintosh laryngoscope (ML) by inexperienced personnel in a simulated manikin difficult airway. METHODS: Twenty-four fifth-year medical students with no previous experience in tracheal intubation participated in this study. We used an advanced patient simulator (SimMan(R), Laerdal Medical, Stavanger, Norway) to simulate difficult airway scenarios including cervical spine rigidity, limited mouth opening, and pharyngeal obstruction. The sequences in selecting devices and scenarios were randomized. Success rates for tracheal intubation, and the time required for visualization of the glottis, tracheal intubation, and inflation of the lungs, and the number of optimization maneuvers and dental click sounds were analyzed. The 3 different intubation devices were tested in 4 different scenarios by 24 students. RESULTS: Both the AWS and ATQ had very high success rates of tracheal intubation compared with the ML (AWS 100%*; ATQ 98%*; and ML 89%; *P < 0.05 AWS, ATQ versus ML). The time to intubation with the AWS was significantly shorter than with the ATQ and ML (AWS 11 +/- 6 seconds; ATQ 16 +/- 12 seconds; and ML 16 +/- 11 seconds; *P < 0.05 AWS versus ATQ, ML). The number of optimization maneuvers with the AWS was significantly lower than with the ATQ and ML. There were significantly more audible dental click sounds with the ML than with the AWS and ATQ. CONCLUSION: Both the AWS and ATQ may be suitable devices for difficult intubation by inexperienced personnel in this manikin simulated scenario. Further studies in a clinical setting are necessary to confirm these findings. PMID- 20357150 TI - Laryngeal mask airway or endotracheal tube for percutaneous dilatational tracheostomy: a comparison of visibility of intratracheal structures. AB - PURPOSE: Some severe complications during percutaneous dilatational tracheostomy (PDT) may be related to poor visualization of tracheal structures. Subjectively, the bronchoscopical view obtained via a laryngeal mask airway (LMA) seems to be better than that obtained with an endotracheal tube (ETT). In this prospective, randomized study, we compared LMA and ETT as the ventilatory device during PDT mainly with respect to visualization of tracheal structures. The quality of ventilation and airway-related complications are also reported. METHODS: In this prospective, randomized study, PDT was performed using an LMA (n = 33) or an ETT (n = 30). Quality of ventilation and visualization of tracheal structures (thyroid, cricoid, and tracheal cartilages) were rated as follows: very good (1), good (2), difficult (3), and not possible (4) with LMA/ETT. A rating of 4 required the alternate airway. Groups were compared using the chi(2) test. RESULTS: Visualization of tracheal structures was better with the LMA: ratings were 1 or 2 in 94% of patients with an LMA, compared with 66% of patients with an ETT (P <0.05). Visual control during puncturing the trachea was 1 or 2 in 97% of patients using an LMA and 77% of patients for an ETT (P < 0.05). A rating of 4 was assigned to 1 patient with an LMA and to 3 patients with an ETT. Hemodynamic variables were similar in both groups. Blood gas analysis during PDT showed decreased Pao(2) in both groups, and increased Paco(2), which was more pronounced with an ETT compared with an LMA (59 +/- 14 mm Hg and 51 +/- 11 mm Hg [P < 0.05]). In the ETT group, 2 patients were extubated accidentally, and in another patient, the bronchoscope was damaged because of insufficient visualization of the tracheal puncture site. CONCLUSION: The LMA technique showed definite advantages regarding visualization of relevant tracheal structures and the dilation process compared with an ETT. This may be especially relevant in the hands of inexperienced intensivists and in cases of difficult patient anatomy where improved structural visualization optimizes operating conditions. PMID- 20357151 TI - Case report: massive blood transfusion in a patient with immunoglobulin a deficiency undergoing cesarean delivery. AB - Patients with immunoglobulin (Ig)A deficiency develop autoantibodies against IgA, which render them vulnerable to severe anaphylactic reactions when transfused with conventional blood or blood products containing IgA. In this report, we describe a patient with IgA deficiency and placenta accreta undergoing emergency cesarean delivery who required massive blood transfusion. We discuss the workup and treatment options in patients with known IgA deficiency. PMID- 20357152 TI - Real-time assessment of perioperative behaviors in children and parents: development and validation of the perioperative adult child behavioral interaction scale. AB - BACKGROUND: Behavior in response to distressful events during outpatient pediatric surgery can contribute to postoperative maladaptive behaviors, such as temper tantrums, nightmares, bed-wetting, and attention seeking. Currently available perioperative behavioral assessment tools have limited utility in guiding interventions to ameliorate maladaptive behaviors because they cannot be used in real time, are only intended to be used during 1 phase of the experience (e.g., perioperative), or provide only a static assessment of the child (e.g., level of anxiety). A simple, reliable, real-time tool is needed to appropriately identify children and parents whose behaviors in response to distressful events at any point in the perioperative continuum could benefit from timely behavioral intervention. Our specific aims were to (1) refine the Perioperative Adult Child Behavioral Interaction Scale (PACBIS) to improve its reliability in identifying perioperative behaviors and (2) validate the refined PACBIS against several established instruments. METHODS: The PACBIS was used to assess the perioperative behaviors of 89 children aged 3 to 12 years presenting for adenotonsillectomy and their parents. Assessments using the PACBIS were made during perioperative events likely to prove distressing to children and/or parents (perioperative measurement of blood pressure, induction of anesthesia, and removal of the IV catheter before discharge). Static measurements of perioperative anxiety and behavioral compliance during anesthetic induction were made using the modified Yale Preoperative Anxiety Scale and the Induction Compliance Checklist (ICC). Each event was videotaped for later scoring using the Child-Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF) and Observational Scale of Behavioral Distress (OSBD). Interrater reliability using linear weighted kappa (kappa(w)) and multiple validations using Spearman correlation coefficients were analyzed. RESULTS: The PACBIS demonstrated good to excellent interrater reliability, with kappa(w) ranging from 0.62 to 0.94. The Child Coping and Child Distress subscores of the PACBIS demonstrated strong concurrent correlations with the modified Yale Preoperative Anxiety Scale, ICC, CAMPIS-SF, and OSBD. The Parent Positive subscore of the PACBIS correlated strongly with the CAMPIS-SF and OSBD, whereas the Parent Negative subscore showed significant correlation with the ICC. The PACBIS has strong construct and predictive validities. CONCLUSIONS: The PACBIS is a simple, easy to use, real-time instrument to evaluate perioperative behaviors of both children and parents. It has good to excellent interrater reliability and strong concurrent validity against currently accepted scales. The PACBIS offers a means to identify maladaptive child or parental behaviors in real time, making it possible to intervene to modify such behaviors in a timely fashion. PMID- 20357153 TI - Accuracy of preoperative electrocardiographic and chest radiographic screening for prediction of left ventricular dysfunction in patients with suspected neuromuscular disorders. AB - BACKGROUND: We sought to determine the reliability of electrocardiography (ECG) and chest radiography (CXR) in predicting left ventricular (LV) dysfunction in patients with suspected neuromuscular disorders (NMDs) undergoing preanesthetic evaluation for muscle biopsy. METHODS: In this retrospective study, 255 patients with a preliminary diagnosis of NMDs based on history, physical examination, and laboratory testing underwent preanesthetic screening before muscle biopsy. The screening included various combinations of ECG, CXR, and transthoracic echocardiography (Echo) to assess perioperative risk associated with potentially undiagnosed LV dysfunction. Multivariate logistic regression analysis was applied to ascertain whether CXR and ECG were independently predictive of LV dysfunction. In addition, receiver-operating characteristic curve analysis was used to assess the diagnostic accuracy of each test and the combination of CXR and ECG in differentiating LV dysfunction from normal function based on Echo "gold standard" data. RESULTS: The study consisted of 255 patients who had a transthoracic Echo, and among these patients, 235 had CXR and 237 had ECG. Forty-four patients were diagnosed by transthoracic Echo to have LV dysfunction (17.3%). Of the 255 patients in the study population, 24 were found to have mild LV dysfunction (9.4%) and 20 had moderate to severe LV dysfunction (7.8%) on Echo. With Echo providing the definitive standard for the diagnosis of LV dysfunction, we found that a CXR alone was predictive in 37% of cases of LV dysfunction, an ECG alone was predictive in 14% of cases, and the combination of both was predictive in 81% of cases. The combination of ECG and CXR test offered the highest diagnostic accuracy (area under the curve of 0.95, P < 0.0001) for differentiating moderate to severe LV dysfunction from normal LV function. CONCLUSIONS: In patients with suspected neuromuscular disease, CXR and ECG provided low independent diagnostic prediction for the presence or absence of LV dysfunction. The combination of both tests can identify cardiomyopathy with relatively high accuracy in children with suspected NMDs independent of age and gender, particularly in patients with moderate to severe LV dysfunction. Although our findings suggest that combination ECG and CXR screening is a reliable means of detecting LV dysfunction, this approach fails to differentiate the severity or type of cardiomyopathy that may exist. Therefore, the decision to obtain a perioperative Echo before muscle biopsy should involve careful consideration of the disease suspected, ECG and CXR results, laboratory studies, patient age, physical examination, and family history. PMID- 20357154 TI - Posttreatment but not pretreatment with selective beta-adrenoreceptor 1 antagonists provides neuroprotection in the hippocampus in rats subjected to transient forebrain ischemia. AB - BACKGROUND: beta-Adrenoreceptor antagonists provide neuroprotection against focal cerebral ischemia, but the effects of these antagonists on experimental global cerebral ischemia are unknown. That is, the effect of beta-adrenoreceptor antagonism in vulnerable brain regions after ischemic insult has not been examined. Therefore, we investigated the neuroprotective effects of preischemic or postischemic administration of propranolol (a nonselective beta-adrenoreceptor antagonist), esmolol, and landiolol (selective beta-adrenoreceptor 1 antagonists) against forebrain ischemia in rats. METHODS: IV administration of saline 10 microL . h(-1), propranolol 100 microg . kg(-1) . min(-1), esmolol 200 microg . kg(-1) . min(-1), or landiolol 50 microg . kg(-1) . min(-1) in male Sprague Dawley rats was started 30 minutes before or 60 minutes after 8-minute bilateral carotid artery occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All drugs were administered continuously until 5 days after reperfusion, and the animals were evaluated neurologically and histologically after this 5-day period. RESULTS: Preischemic treatment with propranolol, esmolol, or landiolol failed to provide neuroprotection against forebrain ischemia in the hippocampus. Rats treated with propranolol tended to have a worse score for motor activity and a higher mortality rate (up to 64%), but the differences with other groups were not statistically significant. Postischemic treatment with esmolol and landiolol, but not with propranolol, reduced neuronal injury after forebrain ischemia. However, motor activity did not differ among rats treated postischemically with any of the beta-adrenoreceptor antagonists or saline. CONCLUSIONS: Postischemic treatment with esmolol and landiolol provided neuroprotection in the hippocampus in rats subjected to bilateral carotid artery occlusion combined with hemorrhagic shock, whereas treatment with propranolol failed to show neuroprotection. We suggest that concomitant beta-blockade and shock might work as a systemic depressant, rather than a neuroprotectant, resulting in exacerbation of cerebral ischemia. PMID- 20357155 TI - Influence of procedure classification on process variability and parameter uncertainty of surgical case durations. AB - BACKGROUND: Predictive variability of operating room (OR) times influences decision making on the day of surgery including when to start add-on cases, whether to move a case from one OR to another, and where to assign relief staff. One contributor to predictive variability is process variability, which arises among cases of the same procedure(s). Another contributor is parameter uncertainty, which is caused by small sample sizes of historical data. METHODS: Process variability was quantified using absolute percentage errors of surgeons' bias-corrected estimates of OR time. The influence of procedure classification on process variability was studied using a dataset of 61,353 cases, each with 1 to 5 scheduled and actual Current Procedural Terminology (CPT) codes (i.e., a standardized vocabulary). Parameter uncertainty's sensitivity to sample size was quantified by studying ratios of 90% prediction bounds to medians. That studied dataset of 65,661 cases was used previously to validate a Bayesian method to calculate 90% prediction bounds using combinations of surgeons' scheduled estimates and historical OR times. RESULTS: (1) Process variability differed significantly among 11 groups of surgical specialty and case urgency (P < 0.0001). For example, absolute percentage errors exceeded the overall median of 22% for 57% of urgent spine surgery cases versus 42% of elective spine surgery cases. (2) Process variability was not increased when scheduled and actual CPTs differed (P = 0.23 without and P = 0.47 with stratification based on the 11 groups), because most differences represented known (planned) options inherent to procedures. (3) Process variability was not associated with incidence of procedures (P = 0.79), after excluding cataract surgery, a procedure with high relative variability. (4) Parameter uncertainty from uncommon procedures (0-2 historical cases) accounted for essentially all of the uncertainty in decisions dependent on estimates of OR times. The Bayesian method moderated the effect of small sample sizes on uncertainty in estimates of OR times. In contrast, from prior work, the use of broad categories of procedures reduces parameter uncertainty but at the expense of increased process variability. CONCLUSIONS: For procedures with few historic data, the Bayesian method allows for effective case duration prediction, permitting use of detailed procedure descriptions. Although fine resolution of scheduling procedures increases the chance of performed procedure(s) differing from scheduled procedure(s), this does not increase process variability. Future studies need both to address differences in process variability among specialties and accept the limitation that findings from one may not apply to others. PMID- 20357156 TI - Analgesic properties of the novel amino acid, isovaline. AB - BACKGROUND: Isovaline, a nonproteinogenic alpha-amino acid rarely found in the biosphere, is structurally similar to the inhibitory neurotransmitters glycine and gamma-aminobutyric acid. Because glycine(A) and gamma-aminobutyric acid receptor agonists are antiallodynic, we hypothesized that isovaline produces antinociception in mice. METHODS: All experiments were performed on female CD-1 mice using a blinded, randomized, and controlled design. The effects of RS isovaline were studied on nociceptive responses to (1) formalin injection into the hindpaw; (2) glutamate injection into the hindpaw; and (3) strychnine injection either into the lumbar intrathecal space or cisterna magna. We determined the effects of IV RS-isovaline (50, 150, or 500 mg/kg; n = 10/dose) or intrathecal RS-, R-, and S-isovaline, glycine, and beta-alanine into the lumbar intrathecal space (5-microL volumes of 60, 125, 250, and 500 mM; n = 9/dose/group) on the response to formalin in the paw. The response to 20 microL intraplantar glutamate (750 mM) was compared with glutamate (750 mM) coadministered with isovaline. We also determined the response to intraplantar strychnine. Lumbar intrathecal (100 microM) or intracisternal (200 microM) injections of strychnine into the lumbar intrathecal space or the cisterna magna were used to induce allodynia as a measure of glycine inhibitory dysfunction. The effects of intrathecal or intracisternal strychnine were compared with isovaline coapplied with the strychnine (n = 8/group). RESULTS: In the formalin paw test, IV isovaline did not change phase I but decreased phase II responses in a dose dependent manner (50% effective dose = 66 mg/kg, n = 10, P < 0.01). There was no effect on rotarod performance, appearance, or behavior of the mouse, and no respiratory depression. Intrathecal isovaline, glycine, and beta-alanine attenuated phase I and II responses (P < 0.01 for each drug). In contrast to beta alanine and glycine, isovaline at maximally effective doses did not produce scratching, biting, or agitation. Intrathecal RS- and S-isovaline attenuated phase I (P < 0.05 for each group) and RS-, R-, and S-isovaline attenuated phase II responses (P < 0.05 for each group), with no significant difference between the efficacies of R- and S-enantiomers. Localized strychnine-induced glycine inhibitory dysfunction was greatly reduced by intracisternal (P < 0.01) and intrathecal (P < 0.01) isovaline. Although intraplantar strychnine did not induce peripheral allodynia, high doses of isovaline did not block the peripheral allodynia induced by glutamate. CONCLUSIONS: Isovaline reduced responses in mouse pain models without producing acute toxicity, possibly by enhancing receptor modulation of nociceptive information. PMID- 20357157 TI - Phenylephrine suppresses the pain modulation of diffuse noxious inhibitory control in rats. AB - BACKGROUND: Diffuse noxious inhibitory control (DNIC) is a phenomenon whereby wide dynamic range neurons are selectively and powerfully inhibited through the central nervous system by noxious stimuli heterotopically applied to a body area distant from their excitatory receptive fields. Previous work has shown that systemic administration of an alpha1-adrenoceptor agonist, phenylephrine (PE), blocked the DNIC. We hypothesized that descending inhibitory pathways mediate the DNIC mechanism and that the neural network of the DNIC loop exists in the middle brainstem, likely in a more rostral part than formerly assumed, possibly the nucleus raphe magnus (RMg). The aim of this study was to determine whether DNIC is directly modulated by PE when administered close to the RMg. METHODS: The experiments were performed on anesthetized male Sprague-Dawley rats. For administration of different drugs close to the RMg, the tip of a 33-gauge cannula was placed into an area close to the RMg as determined using the atlas of Paxinos and Watson. Single square-wave electrical stimuli were applied to the digits of the left hindpaw. The C-fiber reflex response elicited by electrical stimulation within the receptive field of the ipsilateral sural nerve was recorded from the biceps femoris muscle in the absence and presence of noxious tail immersion in warm water at 50 degrees C. The DNIC effect was calculated from a recorded electromyogram as the "inhibition rate." Saline (0.05 microL) or PE (0.05 microg/0.05 microL) was microinjected close to the RMg through the cannula. The C fiber reflex evoked by electromyographic activity was recorded the same way. The inhibition rate of the C-fiber reflex was compared before and after administration of drugs. A paired t test was used for statistical comparison between same drug administration groups, and 1-way analysis of variance and Bonferroni multiple comparison were used for statistical analysis between different drugs. At the end of all experiments, the tissue-contacting end of the cannula tip was cauterized with an electric current to localize the drug administration site. The brain was removed, sliced in coronal sections, and stained with hematoxylin and eosin. RESULTS: The C-fiber reflex inhibited by noxious thermal stimuli (DNIC) was significantly blocked after the injection of PE close to the RMg. CONCLUSION: Direct administration of PE close to the RMg inhibited DNIC, thereby affecting and modulating the intrinsic pain inhibition system. These findings suggest that the RMg may be involved in the regulation of DNIC. PMID- 20357159 TI - Sedation with GPI 15715, a water-soluble prodrug of propofol, using target controlled infusion in volunteers: retraction. PMID- 20357158 TI - A model of intravenous regional anesthesia in rats. AB - BACKGROUND: We developed an IV regional anesthesia (IVRA) model using the tails of rats to allow preclinical evaluation of the safety and efficacy of drugs used in IVRA and analgesia. METHODS: Three sequential experiments were designed to determine local anesthetic and analgesic effects of drugs injected IV in the tail. The anesthesia was assessed by monitoring the response of the tail-clamp (RTC) test on the tail, whereas the analgesia was assessed by recording the latency in the tail-flick test on the tail. In the first 2 experiments, we studied the effects of different environmental temperatures (15 degrees C, 25 degrees C, and 37 degrees C) and length of tourniquet time on the tail-flick and tail-clamp tests, respectively. Based on the outcomes of these 2 experiments, the pharmacological effects of 1% lidocaine (L group) and 0.5% bupivacaine (B group) were compared with normal saline (NS group) to evaluate this model in experiment 3. RESULTS: In experiment 1, compared with its baseline, tail-flick latency increased rapidly in the 15 degrees C group (P < 0.0001), whereas there were no changes in tail-flick latency in the 25 degrees C group (P = 0.3640) and the 37 degrees C group (P = 0.0641) after the first 20 minutes of tail submersion in a water bath. RTCs in all rats were positive during the entire observation period. In experiment 2, tail-flick latency did not change compared with baseline tail flick latency after the first 20 minutes of tourniquet application (P = 0.0902), but significantly increased at the 30-, 40-, 50-, and 60-minute intervals (P = 0.0001). RTCs in all rats were positive during the experiment. In experiment 3, local anesthesia was generated in the tail (distal to the tourniquet) in the L and B groups with a similar onset time of anesthesia (approximately 1 minute), but with a longer recovery time of anesthesia and analgesia in the B group (56.0 +/- 22.0 minutes) than the L group (31.0 +/- 19.0 minutes), whereas no anesthetic and analgesic effects were observed in the NS group. CONCLUSIONS: A reliable model for studying IVRA and analgesia has been developed in rats. PMID- 20357160 TI - Cochrane corner: sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade. AB - BACKGROUND: Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs). OBJECTIVES: To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information. SELECTION CRITERIA: All randomized controlled trials (RCTs) on adult patients (> or = 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers. DATA COLLECTION AND ANALYSIS: We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta- analytic techniques. MAIN RESULTS: We included18 RCTs (n=1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T2 reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P=0.59, I2=0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P=0.95, I2=43%, 3 RCTs). AUTHORS' CONCLUSIONS: Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes. PMID- 20357161 TI - Cochrane corner: hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. AB - BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcome parameters. We aimed to perform individual patient data analysis if data were available, and to from subgroups according to the cardiac arrest situation. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007 Issue 1); MEDLINE (1971 to January 2007); EMBASE (1987 to January 2007); CINAHL (1988 to January 2007); PASCAL (2000 to January 2007); and BIOSIS (1989 to January 2007). SELECTION CRITERIA: We included all randomized controlled trials assessing the effectiveness of the therapeutic hypothermia in patients after cardiac arrest without language restrictions. Studies were restricted to adult populations cooled with any cooling method applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: Validity measures, the intervention, outcome parameters and additional baseline variables were entered into the database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies individual patient data were available. MAIN RESULTS: Four trials and one abstract reporting on 481 patients were included in the systematic review. Quality of the included studies was good in three out of five included studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods patients in the hypothermia group were more likely to reach a best cerebral performance categories score of one or two (CPC, five point scale; 1=good cerebral performance, to 5=brain death) during hospital stay (individual patient data; RR, 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR, 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies there was no significant difference in reported adverse events between hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines. PMID- 20357162 TI - Requested retraction of six studies on the PK/PD and tolerability of fospropofol. PMID- 20357163 TI - The genetics of malignant hyperthermia and related muscular syndromes. PMID- 20357164 TI - Iatrogenic hypoalbuminemia due to hydroxyethyl starch 130/0.4: a risk factor for acute kidney injury? PMID- 20357165 TI - Pretreatment time with norbinaltorphimine. PMID- 20357166 TI - Is a 5-year follow-up for addicted attendings who entered a physicians health program valuable information? PMID- 20357167 TI - Retrieval of aspirated nasopharyngeal airway using foley catheter. PMID- 20357168 TI - Downfolding of the epiglottis during intubation. PMID- 20357169 TI - Airway pressure waveform transduced from central venous catheter indicating catheter migration. PMID- 20357172 TI - Review of the 23rd annual meeting of the Society for Pediatric Anesthesia: practice improvement. PMID- 20357173 TI - ESAs in dialysis patients: are you a hedgehog or a fox? PMID- 20357174 TI - Genistein aglycone does not affect thyroid function: results from a three-year, randomized, double-blind, placebo-controlled trial. AB - CONTEXT AND OBJECTIVE: Genistein aglycone positively affects postmenopausal symptoms. However, questions about its long-term safety on the thyroid gland still remain. DESIGN: The parent study was a randomized, double-blind, placebo controlled trial involving 389 osteopenic, postmenopausal women for 24 months. A subcohort (138 patients) continued therapy for an additional year. SETTING: Patients received ambulatory care. PATIENTS AND INTERVENTIONS: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67), plus calcium and vitamin D(3) at therapeutic doses. Circulating thyroid hormones (TSH, free T(3), free T(4)) and autoantibodies (thyroid peroxidase, thyroglobulin, and thyroid microsomal antigen) were assessed in 40 genistein and 37 placebo subjects who completed 3 yr. Thyroid hormone receptor (THRalpha and THRbeta) and retinoid receptor (RARalpha, RARgamma, and RXRalpha) expression from peripheral blood monocytes was also evaluated at baseline, 12, 24, and 36 months in all 3-yr completers. RESULTS: Genistein administration over 3 yr did not affect serum thyroid hormones or autoantibodies. In addition, there were no differences in THRalpha, THRbeta, RARalpha, RARgamma, or RXRalpha mRNA expression between groups. CONCLUSION: These data suggest that genistein aglycone intake does not significantly increase the risk of clinical or subclinical hypothyroidism at the dose of 54 mg/d. PMID- 20357175 TI - Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas. AB - CONTEXT: Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. METHODS: Eighty five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. RESULTS: Cabergoline normalized hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 microadenomas disappeared. Eighty patients (94%) conceived 95 pregnancies, two of which were cabergoline-free second pregnancies. The dose of cabergoline at the first pregnancy was 0.25-9 mg/wk overall and 2-9 mg/wk in the resistant patients. Of the 93 pregnancies achieved on cabergoline, 86 resulted in 83 single live births, one stillbirth, and two abortions; the remaining seven were ongoing. All babies were born healthy, without any malformations. No mothers experienced impaired vision or headache suggestive of abnormal tumor reexpansion throughout pregnancy. CONCLUSION: Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumor size and bromocriptine resistance or intolerance. Cabergoline monotherapy could substitute for the conventional combination therapy of pregestational surgery or irradiation plus bromocriptine in macroprolactinomas. PMID- 20357176 TI - Age in men does not determine gonadotropin-releasing hormone's dose-dependent stimulation of luteinizing hormone secretion under an exogenous testosterone clamp. AB - BACKGROUND: Aging is associated with a decline in incremental LH pulse amplitude, which could be due to decreased GnRH secretion or impaired GnRH action. HYPOTHESIS: Inconsistent published studies of GnRH action in older men may be due to disparate sex-steroid milieus. FACILITY: This study was conducted at a clinical translational-research unit. SUBJECTS: We studied 16 healthy men (8 young men and 8 older men). METHODS: An overnight transdermal testosterone (T) clamp was implemented before randomly ordered injections of 0, 2.5, 10, 25, 250, and 750 ng GnRH on separate days (96 study sessions). OUTCOMES: LH responses were quantified by variable-waveform deconvolution analysis. RESULTS: The T clamp maintained age-invariant mean concentrations of total, bioavailable, and free T, SHBG, LH, FSH, and prolactin. By two-way analysis of covariance, GnRH dose (P < 0.001) but not age (0.15 < or = P < or = 0.83) determined mean, peak, incremental, and pulsatile LH responses. Statistical power (median) was 95, 98, 90, and 99% to detect a 30% or greater age contrast at P < or = 0.05 in mean, peak, incremental, and pulsatile LH responses, and greater than 99% to detect a 30% or greater age contrast in bioavailable or total T concentrations. Higher GnRH doses (P < 0.001) abbreviated LH secretory bursts in both age groups. CONCLUSION: In the face of eugonadal concentrations of total, bioavailable, and free T, young and older men exhibit remarkably similar LH responses to a 300-fold dose range of exogenous GnRH. Accordingly, previously reported disparate effects of age on GnRH action may reflect in part age-discrepant sex-steroid milieus. PMID- 20357177 TI - Near normalization of adult height and body proportions by growth hormone in pycnodysostosis. AB - CONTEXT: Mutations in the cathepsin K gene (CTSK) cause a very rare form of short limb dwarfism called pyknodysostosis (online inheritance in man 265800) that reduces adult height to 130-150 cm. OBJECTIVE: To study the effects of GH in children with pyknodysostosis. DESIGN AND METHODS: This was a pilot open study of three children with pyknodysostosis (P1, P2, P3) and 16 age-matched children with idiopathic short stature (ISS) treated with a similar IGF-I-based dosing of GH therapy. P1, P2, and P3 received a mean GH dose of 29, 67, and 120 microg/kg x d, respectively, during 12, 6.5, and 5 yr, whereas the ISS group received a mean dose of 62 +/- 21 microg/kg x d during 5.4 +/- 2 yr. RESULTS: P1, P2, and P3 had the typical clinical and radiological features of pyknodysostosis. They were shown to carry three different homozygous missense mutations of the CTSK gene. After onset of GH at 4.5, 5.4, and 10.9 yr of age, respectively, height increased from -2, -4.2, and -3 SD score to -1, -0.5, and -1 SD score after a 12, 6.5, and 5 yr GH treatment. Remarkably, body disproportion was largely corrected by GH treatment. IGF-I levels in P1, P2, and P3 were within the range of the ISS group. CONCLUSIONS: Pyknodysostotic patients can reach near-normal stature and skeletal proportions with a personalized GH treatment targeted at appropriate IGF-I levels. Given the severity of this rare dwarfism, we propose that GH should be offered to affected children. PMID- 20357178 TI - A heterozygous mutation of the insulin-like growth factor-I receptor causes retention of the nascent protein in the endoplasmic reticulum and results in intrauterine and postnatal growth retardation. AB - BACKGROUND: Mutations in the IGF-I receptor (IGF1R) gene can be responsible for intrauterine and postnatal growth disorders. OBJECTIVE: Here we report on a novel mutation in the IGF1R gene in a female patient. The aim of our study was to analyze the functional impact of this mutation. PATIENT: At birth, the girl's length was 47 cm [-1.82 sd score (SDS)], and her weight was 2250 g (-2.26 SDS). Clinical examination revealed microcephaly and retarded cognitive development. She showed no postnatal catch-up growth but had relatively high IGF-I levels (+1.83 to +2.17 SDS). RESULTS: Denaturing HPLC screening and direct DNA sequencing disclosed a heterozygous missense mutation resulting in an amino acid exchange from valine to glutamic acid at position 599 (V599E-IGF1R). Using various cell systems, we found that the V599E-IGF1R mutant was not tyrosine phosphorylated and had an impaired downstream signaling in the presence of IGF-I. Flow cytometry and live cell confocal laser scanning microscopy revealed a lack of cell surface expression due to an extensive retention of V599E-IGF1R proteins within the endoplasmic reticulum. CONCLUSION: The V599E-IGF1R mutation interferes with the receptor's trafficking path, thereby abrogating proreceptor processing and plasma membrane localization. Diminished cell surface receptor density solely expressed from the patient's wild-type allele is supposed to lead to insufficient IGF-I signaling. We hypothesize that this mechanism results in intrauterine and postnatal growth retardation of the affected patient. The reported retention of the nascent IGF1R in the endoplasmic reticulum presents a novel mechanism of IGF I resistance. PMID- 20357179 TI - Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. AB - Breathing-disordered states, such as in obstructive sleep apnea, which are cyclical in nature, have been postulated to induce neurocognitive morbidity in both pediatric and adult populations. The oscillatory nature of intermittent hypoxia, especially when chronic, may mimic the paradigm of ischemia-reperfusion in that tissues and cells are exposed to episodes of low and high O(2) and this may lead to oxidant stress. Therefore, we decided to explore the potential contribution of oxidant stress in our intermittent hypoxia/hypercapnia animal model and the role that mitochondria might play in this stress. Neonatal mice were exposed to intermittent hypoxia/hypercapnia for 10 days and 2 wk. Combined intermittent hypoxia/hypercapnia led to a marked increase in apoptotic cell death in the cerebral cortex. Oxygen consumption studies in isolated mitochondria from intermittent hypoxia/hypercapnia-exposed brains demonstrated significant reductions in both state 4 and state 3 respiratory activities by approximately 60% and 75%, respectively. Electron paramagnetic resonance spectroscopy registered a significant increase in superoxide production during nonphosphorylating state 4 by 37%, although superoxide leakage during state 3 did not increase upon treatment. Neuronal superoxide-specific dihydroethidium oxidation was also greater in exposed animals. These studies indicate that intermittent hypoxia/hypercapnia leads to oxidative stress due to mitochondrial response within the mouse central nervous system. PMID- 20357181 TI - Regulation of muscle force in the absence of actin-myosin-based cross-bridge interaction. AB - For the past half century, the sliding filament-based cross-bridge theory has been the cornerstone of our understanding of how muscles contract. According to this theory, active force can only occur if there is overlap between the contractile filaments, actin and myosin. Otherwise, forces are thought to be caused by passive structural elements and are assumed to vary solely because of the length of the muscle. We observed increases in muscle force by a factor of 3 to 4 above the purely passive forces for activated and stretched myofibrils in the absence of actin-myosin overlap. We show that this dramatic increase in force is crucially dependent on the presence of the structural protein titin, cannot be explained with calcium activation, and is regulated by actin-myosin-based cross bridge forces before stretching. We conclude from these observations that titin is a strong regulator of muscle force and propose that this regulation is based on cross-bridge force-dependent titin-actin interactions. These results suggest a mechanism for stability of sarcomeres on the "inherently unstable" descending limb of the force-length relationship, and they further provide an explanation for the protection of muscles against stretch-induced muscle injuries. PMID- 20357180 TI - Autophagy in health and disease. 5. Mitophagy as a way of life. AB - Our understanding of autophagy has expanded greatly in recent years, largely due to the identification of the many genes involved in the process and to the development of better methods to monitor the process, such as green fluorescent protein-LC3 to visualize autophagosomes in vivo. A number of groups have demonstrated a tight connection between autophagy and mitochondrial turnover. Mitochondrial quality control is the process whereby mitochondria undergo successive rounds of fusion and fission with a dynamic exchange of components to segregate functional and damaged elements. Removal of the mitochondrion that contains damaged components is accomplished via autophagy (mitophagy). Mitophagy also serves to eliminate the subset of mitochondria producing the most reactive oxygen species, and episodic removal of mitochondria will reduce the oxidative burden, thus linking the mitochondrial free radical theory of aging with longevity achieved through caloric restriction. Mitophagy must be balanced by biogenesis to meet tissue energy needs, but the system is tunable and highly dynamic. This process is of greatest importance in long-lived cells such as cardiomyocytes, neurons, and memory T cells. Autophagy is known to decrease with age, and the failure to maintain mitochondrial quality control through mitophagy may explain why the heart, brain, and components of the immune system are most vulnerable to dysfunction as organisms age. PMID- 20357182 TI - Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling. AB - Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells. PMID- 20357183 TI - Normal targeting of a tagged Kv1.5 channel acutely transfected into fresh adult cardiac myocytes by a biolistic method. AB - The transfection of cardiac myocytes is difficult, and so most of the data regarding the regulation of trafficking and targeting of cardiac ion channels have been obtained using heterologous expression systems. Here we apply the fast biolistic transfection procedure to adult cardiomyocytes to show that biolistically introduced exogenous voltage-gated potassium channel, Kv1.5, is functional and, like endogenous Kv1.5, localizes to the intercalated disc, where it is expressed at the surface of that structure. Transfection efficiency averages 28.2 +/- 5.7% of surviving myocytes at 24 h postbombardment. Ventricular myocytes transfected with a tagged Kv1.5 exhibit an increased sustained current component that is approximately 40% sensitive to 100 microM 4-aminopyridine and which is absent in myocytes transfected with a fluorescent protein-encoding construct alone. Kv1.5 deletion mutations known to reduce the surface expression of the channel in heterologous cells similarly reduce the surface expression in transfected ventricular myocytes, although targeting to the intercalated disc per se is generally unaffected by both NH(2)- and COOH-terminal deletion mutants. Expressed current levels in wild-type Kv1.5, Kv1.5DeltaSH3(1), Kv1.5DeltaN209, and Kv1.5DeltaN135 mutants were well correlated with apparent surface expression of the channel at the intercalated disc. Our results conclusively demonstrate functionality of channels present at the intercalated disc in native myocytes and identify determinants of trafficking and surface targeting in intact cells. Clearly, biolistic transfection of adult cardiac myocytes will be a valuable method to study the regulation of surface expression of channels in their native environment. PMID- 20357184 TI - Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme. AB - Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechanisms free heme [Fe(III)-protoporphyrin IX (FP)] might contribute to the dysregulation of L arginine (L-Arg) metabolism and bioavailability. Carrier systems "y+" [or cationic amino acid transporter (CAT)] and "y+L" transport L-Arg into red blood cells (RBC), where it is hydrolyzed to ornithine and urea by arginase (isoform I) or converted to NO* and citrulline by endothelial nitric oxide synthase (eNOS). Our results show a significant and dose-dependent impairment of L-Arg transport into RBC pretreated with FP, with a strong inhibition of the system carrier y+L. Despite the impaired L-Arg influx, higher amounts of L-Arg-derived urea are produced by RBC preexposed to FP caused by activation of RBC arginase I. This activation appeared not to be mediated by oxidative modifications of the enzyme. We conclude that L-Arg transport across RBC membrane is impaired and arginase mediated L-Arg consumption enhanced by free heme. This could contribute to reduced NO production in severe malaria. PMID- 20357185 TI - The glitter of gold: biolistic transfection of fresh adult cardiac myocytes. Focus on "normal targeting of a tagged Kv1.5 channel acutely transfected into fresh adult cardiac myocytes by a biolistic method". PMID- 20357186 TI - Homocysteine: to measure or not to measure? Focus on "functional NMDA receptors in rat erythrocytes". PMID- 20357187 TI - An essential role of PDCD4 in vascular smooth muscle cell apoptosis and proliferation: implications for vascular disease. AB - It is well established that vascular smooth muscle cell (VSMC) apoptosis and proliferation are critical cellular events in a variety of human vascular diseases. However, the molecular mechanisms involved in controlling VSMC apoptosis and proliferation are still unclear. In the current study, we have found that programmed cell death 4 (PDCD4) is significantly downregulated in balloon-injured rat carotid arteries in vivo and in platelet-derived growth factor-stimulated VSMCs in vitro. Overexpression of PDCD4 via adenovirus (Ad PDCD4) increases VSMC apoptosis in an apoptotic model induced by serum deprivation. In contrast, VSMC apoptosis is significantly decreased by knockdown of PDCD4 via its small interfering RNA. In the rat carotid arteries in vivo, VSMC apoptosis is increased by Ad-PDCD4. We have further identified that activator protein 1 is a downstream signaling molecule of PDCD4 that is associated with PDCD4-mediated effects on VSMC apoptosis. In addition, VSMC proliferation was inhibited by overexpression of PDCD4. The current study has identified, for the first time, that PDCD4 is an essential regulator of VSMC apoptosis and proliferation. The downregulation of PDCD4 expression in diseased vascular walls may be responsible for the imbalance of VSMC proliferation and apoptosis. The results indicate that PDCD4 may be a new therapeutic target in proliferative vascular diseases. PMID- 20357188 TI - Altered expression of metallothionein-I and -II and their receptor megalin in inherited photoreceptor degeneration. AB - PURPOSE: To examine in rodent models of retinitis pigmentosa (RP) the expression of the neuroprotectants metallothionein-I and -II and of megalin, an endocytic receptor that mediates their transport into neurons. METHODS: Gene and protein expression were analyzed in retinas of rd1 and rds mice and in those of RCS (Royal College of Surgeons) rats of various ages. Glial cell markers (cellular retinaldehyde binding protein, CRALBP; glial fibrillary acidic protein, GFAP; CD11b; and isolectin B4) were used to establish the identity of the cells. RESULTS: Metallothionein-I and -II gene expression increased with age in normal and degenerating retinas and was significantly greater in the latter. Protein expression, corresponding to metallothionein-I+II, was first observed in rd1 mice in Muller cells at postnatal day (P)12 and in rds mice at P16, coinciding with the onset of GFAP expression in these cells. In RCS rats, the same distribution was observed, but not until P32, long after the onset of GFAP expression. Metallothionein-I+II was observed also in a small number of microglial cells. Megalin was expressed in the nerve fiber layer and in the region of the inner and outer segments in normal animals, but expression in the outer retina was lost with age in degenerating retinas. CONCLUSIONS: Induction of metallothionein-I and -II occurs in the RP models studied and correlates with glial activation. The progressive loss of megalin suggests that transport of metallothionein-I+II into the degenerating photoreceptors (from e.g., Muller cells), could be impaired, potentially limiting the actions of these metallothioneins. PMID- 20357189 TI - Effect of bevacizumab on strabismus surgery in rabbits. AB - PURPOSE: This study was conducted to evaluate the effect of bevacizumab on postoperative inflammation and adhesion after strabismus surgery in rabbits. METHODS: Fifteen New Zealand White rabbits were used for this study. Both eyes of each of 15 rabbits underwent reinsertion of the superior rectus muscle (SRM). The right eye of each animal received a subconjunctival bevacizumab injection (2.5 mg/0.1 mL). As controls, normal saline was injected subconjunctivally in the contralateral eye. To assess acute inflammation changes, macrophages, neutrophils, and monocytes were localized in the SRM using an anti-CD11b antibody at postoperative day 1. At 4 weeks, the sites of muscle reattachment were evaluated grossly for postoperative adhesion score and histologically for collagen formation. RESULTS: Infiltration of acute inflammatory cells showing CD11b+ was significantly reduced in the bevacizumab injection group (P=0.001). The difference in adhesion (SRM/conjunctiva and SRM/sclera) scores between the two groups was statistically insignificant (P=0.93 and P=0.85). Histopathologic findings revealed that muscle changes and fibrosis showed no significant difference (P=0.69) between the treated eyes and the control eyes. CONCLUSIONS: The intraoperative use of bevacizumab reduced inflammatory cell infiltration in the early stage of the procedure, but it was insufficient to prevent postoperative adhesion in rabbit eyes after extraocular muscle surgery. PMID- 20357190 TI - Retinal protection from acute glaucoma-induced ischemia-reperfusion injury through pharmacologic induction of heme oxygenase-1. AB - PURPOSE: To investigate the protective effects of cobalt protoporphyrin (CoPP), a potent heme oxygenase (HO)-1 inducer, in a rat model of ischemia-reperfusion injury and to document the possible antiapoptotic and anti-inflammatory mechanisms underlying the protection. METHODS: Rats pretreated with intraperitoneal injection of CoPP (5 mg/kg) were subjected to retinal ischemia by increases in intraocular pressure to 130 mm Hg for 60 minutes. The protective effects of CoPP were evaluated by determining the morphology of the retina, counting the survival of retinal ganglion cells (RGCs), and measuring apoptosis in retinal layers. In addition, expressions of HO-1, caspase-3, p53, Bcl-xL, monocyte chemoattractant protein (MCP)-1, and inducible nitric oxide synthase (iNOS) were documented by Western blot analysis. Detection of HO-1, NF-kappaB, and CD68 protein in the retina was performed by immunohistochemistry or immunofluorescence. RESULTS: Pharmacologic induction of HO-1 by CoPP led to HO-1 expression in the full retinal layer. HO-1 overexpression alleviated apoptosis in the retina, preserved RGCs, and attenuated the reduction of inner retinal thickness after ischemia-reperfusion injury. Concurrently, overexpression of HO-1 was associated with inhibition of caspase-3, p53, NF-kappaB, and iNOS and with increased expression of Bcl-xL. Meanwhile, the anti-inflammatory effect of HO-1 was related to reduction in the recruitment of macrophage infiltration in the retina through the suppression of MCP-1. These beneficial effects of HO-1 induced by CoPP were diminished by the HO-1 inhibitor ZnPP. CONCLUSIONS: Overexpression of HO-1 by pharmacologic induction protected the retina from subsequent cellular damage caused by ischemia-reperfusion injury through antiapoptotic and anti inflammatory effects. PMID- 20357191 TI - Functional MRI signal changes in primary visual cortex corresponding to the central normal visual field of patients with primary open-angle glaucoma. AB - PURPOSE: To investigate, by functional magnetic resonance imaging (fMRI), the impact of glaucomatous neuropathy of primary open-angle glaucoma (POAG) on neuronal activity in the primary visual cortex, which corresponds to the central normal visual field. METHODS: Six POAG patients with asymmetric visual field damage and spared central vision were enrolled in the study. All patients underwent detailed ophthalmic examinations, including visual acuity, intraocular pressure, refraction, gonioscopy, and fundus examination. Scanning laser polarimetry with variable corneal compensation, confocal scanning laser ophthalmoscopy, posterior segment optical coherence tomography (OCT), and SITA standard 30-2 and 10-2 visual field perimetry were also performed on each patient. Block-design fMRI was then performed. The stimulus was a hemifield checkerboard contrast, reversing at 8 Hz and viewed by the examined eye monocularly during fMRI scanning, with the fellow eye occluded. RESULTS: The blood oxygen level-dependent (BOLD) fMRI signal change in the primary visual cortex corresponding to central visual input from the more severely affected eye was less than that of the fellow eye. Such a difference in fMRI response did not correlate with interocular differences in measurements of scanning laser polarimetry, OCT, and scanning laser ophthalmoscopy, but showed a negative correlation with interocular pattern SD (PSD) difference of visual field analysis. CONCLUSIONS: Glaucomatous neuropathy from POAG may lead to decreased cortical activity in the primary visual cortex, which corresponds to the central normal visual field. The resultant cortical depression is not related to interocular differences in results of polarimetry, OCT, and ophthalmoscopy, but is negatively correlated with PSD of visual field analysis. PMID- 20357192 TI - Time course changes of oxidative stress markers in a rat experimental glaucoma model. AB - PURPOSE: To evaluate the relationship between oxidative stress markers and increased intraocular pressure in experimental glaucoma. METHODS: In vivo chemiluminescence (CL), total antioxidant capacity (TRAP), nitrite concentration (NC), and lipid peroxidation markers (TBARS) were evaluated. Wistar rats (n=18 for each time point) underwent operation, and two episcleral veins were cauterized. RESULTS: Decreases of 22%, 35%, and 27% at 7, 15, and 30 days and an increase of 22% at 60 days in CL were observed in glaucomatous eyes. In optic nerve, TBARS values were 6.9+/-0.5 nmol/mg protein (7 days), 9.4+/-0.4 nmol/mg protein (15 days), 18.0+/-1.2 nmol/mg protein (30 days), and 43.1+/-5.3 nmol/mg protein (60 days) (control, 6.2+/-0.4 nmol/mg protein; P<0.001). NC was 37.0+/ 1.8 microM (7 days), 31.4+/-1.2 microM (15 days), 39.6+/-1.3 microM (30 days), and 40.0+/-1.3 microM (60 days) (control, 21.1+/-1.7 microM; P<0.001). In glaucomatous vitreous humor, TRAP decreased by 42% at 15 days and 78% at 60 days (control, 414+/-29 microM; P<0.001). In glaucomatous aqueous humor, TRAP values were 75+/-7 microM (7 days), 54+/-4 microM (15 days), 25+/-4 microM (30 days), and 50+/-3 microM (60 days) (control, 90+/-10 microM; P<0.001). CONCLUSIONS: Reactive species were increased in glaucoma, as evidenced by the increases in CL, TBARS, and NC. The decrease in the antioxidant levels may be a consequence of an increase in oxidative processes. PMID- 20357193 TI - Methyl palmitate: a potent vasodilator released in the retina. AB - PURPOSE: To determine whether palmitic acid methyl ester (PAME) or methyl palmitate is the retina-derived relaxing factor (RRF). METHODS: A superfusion bioassay cascade technique was used with rat isolated retina as donor tissue and rat aortic ring as detector tissue. The superfusate was analyzed with gas chromatography/mass spectrometry (GC/MS). The biochemical and pharmacologic characteristics of RRF and PAME were compared. RESULTS: The authors demonstrated that the retina on superfusion with Krebs solution spontaneously released RRF (indicated by aortic ring relaxation) and PAME (measured by GC/MS). The release of RRF and PAME was calcium dependent because the release was abolished when the retinas were superfused with calcium-free Krebs solution. Furthermore, aortic relaxations induced by RRF and PAME were not affected after heating their solutions at 70 degrees C for 1 hour, suggesting that both are heat stable. Exogenous PAME concentration dependently induced aortic relaxation with EC50 of 0.82+/-0.75 pM. The aortic relaxations induced by RRF and exogenous PAME were inhibited by 4-aminopyridine (2 mM) and tetraethylammonium (TEA, 10 mM) but were not affected by TEA at 1 mM or 3 mM, glibenclamide (3 microM), or iberiotoxin (100 nM). The vasodilator activity of Krebs solution containing RRF or exogenous PAME was greatly attenuated after hexane extraction. CONCLUSIONS: RRF and PAME share similar biochemical properties and react similarly to all pharmacologic inhibitors examined. Both act primarily on the voltage-dependent K+ (Kv) channel of aortic smooth muscle cells, causing aortic relaxation. These results suggest that PAME is the hydrophobic RRF. PMID- 20357194 TI - Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration. AB - PURPOSE: To investigate, with the use of spectral-domain optical coherence tomography (SD-OCT), microstructural alterations over time in eyes with progressive geographic atrophy (GA) due to age-related macular degeneration. METHODS: Forty-six eyes of 26 patients (median age, 77.9 years [interquartile range (IQR), 71.8-81.0]) with GA without evidence of active or previous neovascular disease at baseline were examined by simultaneous confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT. Serial examinations with alignment of follow-up to baseline scans were performed over a median period of 12.2 months (IQR, 10.2-15.3). Longitudinal SD-OCT variations were evaluated, including quantification of retinal thickness (RT) change and lateral spread of GA (LSGA) at a temporal, nasal, inferior, and superior GA border-section in each eye. RESULTS: GA-enlargement was characterized by progressive loss of the outer hyperreflective SD-OCT bands and by thinning of the outer nuclear layer with subsequent approach of the outer plexiform layer toward Bruch's membrane. In the perilesional zone, various dynamic changes were recorded, including migration of hyperreflective material and changes in drusen height. At the borders, there was a median RT change of -14.09 microm/y (IQR -26.21 to -7.48 microm/y). The median LSGA was 106.90 microm/y (IQR, 55.44-161.70 microm/y). Both parameters showed only moderate intraocular agreement (RT change: intraclass correlation coefficient [ICC], 0.54; 95% CI, 0.39-0.67; LSGA: ICC, 0.49; 95% CI, 0.34-0.64) and no statistical significant difference for one location (RT change, P = 0.125; LSGA, P = 0.516; likelihood ratio test). CONCLUSIONS: Combined cSLO and SD-OCT imaging provides unprecedented insight into dynamic microstructural changes of GA enlargement that may help to better understand the pathogenesis of the disease. Quantitative progression data indicate local factors may exist that drive progression in junctional areas (ClinicalTrials.gov number, NCT00393692). PMID- 20357195 TI - Detection of cystoid macular edema with three-dimensional optical coherence tomography versus fluorescein angiography. AB - PURPOSE: To compare the sensitivity and reproducibility of three-dimensional optical coherence tomography (3D-OCT) and fluorescein angiography (FA) for the detection of cystoid macular edema (CME). METHODS: Data were retrospectively collected from all patients who underwent digital FA and 512 * 128 horizontal raster 3D-OCT scans on the same day in a retina subspecialty clinic. Images were reviewed independently by four reading center graders and adjudicated as a group to render a single result for each eye and each imaging modality. The kappa statistic was used to determine the level of agreement between graders for each modality. The sensitivity of each imaging modality for CME detection was calculated by using the presence of CME on either modality as the ground truth; subgroup analysis was performed according to disease diagnosis and lens status. RESULTS: Four hundred thirteen eyes of 207 patients were included in the analysis. Intergrader agreement was higher for 3D-OCT than for FA both before (kappa(OCT) = 0.61, kappa(FA) = 0.43) and after adjudication (kappa(OCT) = 0.74, kappa(FA) = 0.58).The sensitivity for detection of definite CME was higher for 3D OCT (95%, 144/151 cases) than for FA (44%, 67/151 cases). Definite FA (+) 3D-OCT (-) CME was identified in 1 eye (0.2%), whereas definite FA (-) 3D-OCT (+) CME was identified in 40 eyes (10%). No significant associations between CME detection and lens examination or disease diagnosis were observed. CONCLUSIONS: In this study, 3D-OCT was more sensitive and had better intergrader agreement than did FA for the detection of CME. PMID- 20357196 TI - Effects of topical phenylephrine and tafluprost on optic nerve head circulation in monkeys with unilateral experimental glaucoma. AB - PURPOSE: To compare the effects of a topical alpha agonist (vasoconstrictor) and a prostaglandin receptor (FP) agonist (vasodilator) on circulation in the optic nerve head (ONH) in experimental glaucomatous and normal eyes of monkeys. METHODS: Tissue blood velocity in the ONH (NB(ONH)) was determined using the laser speckle method in both eyes of eight normal cynomolgus monkeys under systemic anesthesia for 180 minutes after bilateral instillation of 5% phenylephrine. The effect of 0.0015% tafluprost, a potent FP agonist, was also studied after single and once-daily 7-day instillations. Measurements were repeated in both eyes of the eight monkeys after establishment of unilateral laser-induced glaucoma. RESULTS: NB(ONH) decreased significantly in both eyes of normal monkeys 30 to 120 minutes after phenylephrine instillation by a maximum of 9% to 11% (P < 0.05) without significant change in intraocular pressure (IOP). A similar decrease in NB(ONH) was found in non-laser-treated eyes in glaucomatous monkeys despite the absence of significant changes in contralateral experimental glaucomatous eyes. NB(ONH) increased by 16% (P < 0.05) 60 minutes after a single instillation and also after 7-day repeated instillations of tafluprost in both eyes of normal monkeys. A similar increase in NB(ONH) occurred in both eyes after the establishment of unilateral glaucoma but was completely abolished by 5 mg/kg indomethacin injected intravenously 15 minutes after tafluprost instillation. Tafluprost significantly reduced IOP only in experimental glaucomatous eyes by 34%. CONCLUSIONS: The ONH vasculature in glaucomatous and normal eyes reacts differently to an exogenous alpha agonist, whereas it reacts similarly to an FP agonist. PMID- 20357197 TI - Reduced expression of aquaporin-9 in rat optic nerve head and retina following elevated intraocular pressure. AB - PURPOSE: To investigate the effect of chronically elevated intraocular pressure (IOP) on the expression of water channel aquaporins (AQPs) 1, 4, and 9 in the optic nerve and retina in rats. METHODS: Three episcleral veins were cauterized to elevate IOP in the left eyes of Sprague-Dawley rats. IOPs were monitored with a rebound tonometer. At 2 and 4 weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and desheathed optic nerves were subjected to gene expression analyses. RESULTS: IOP was significantly increased after surgery up to 4 weeks (P=0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and AQP9 immunoreactivities colabeled for glial fibrillary acidic protein but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 was expressed in Muller cell endfeet, and AQP9 was expressed primarily in NeuN-positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1. CONCLUSIONS: AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Given that AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy. PMID- 20357199 TI - An agonistic TrkB mAb causes sustained TrkB activation, delays RGC death, and protects the retinal structure in optic nerve axotomy and in glaucoma. AB - PURPOSE: Brain-derived neurotrophic factor (BDNF) receptors TrkB and p75(NTR) are expressed in the retina. However, exogenous BDNF does not provide retinal ganglion cells (RGCs) with long-lasting neuroprotection in vivo during optic nerve axotomy or in glaucoma rat models of neurodegeneration. The authors set out to answer the hypothesis that a selective TrkB agonist might afford more efficient neuroprotection. METHODS: Animal models of acute neurodegeneration (complete optic nerve axotomy) and chronic neurodegeneration (ocular hypertension, glaucoma) were used. After intravitreal delivery of test agents or controls, surviving RGCs were quantified. Transient or sustained activation of TrkB receptors in vivo was quantified by Western blot analysis retinal samples for TrkB-phosphotyrosine. Time-dependent changes to the neuronal retinal layers were quantified longitudinally by Fourier domain-optical coherence tomography. RESULTS: The authors show that a selective TrkB agonist caused long-lived TrkB activation and significantly delayed RGC death in these models of acute and chronic retinal injury in vivo. Importantly, using noninvasive retinal imaging, they also show that a selective TrkB agonist caused preservation of the retinal structure in both animal models, with maintenance of the layers comprising neurons and neuronal fibers. CONCLUSIONS: In animal models of acute and chronic neurodegeneration, a TrkB agonist affords long-lasting neuroprotection by causing sustained TrkB activation. The use of structural end points could have prognostic value to evaluate neuroprotection. This work contributes to the understanding of neurotrophic mechanisms underlying RGC death in glaucoma and optic nerve axotomy. PMID- 20357198 TI - Linkage of posterior amorphous corneal dystrophy to chromosome 12q21.33 and exclusion of coding region mutations in KERA, LUM, DCN, and EPYC. AB - PURPOSE: To identify the genetic basis of posterior amorphous corneal dystrophy (PACD) segregating in a large pedigree. METHODS: The authors performed clinical evaluation of a previously unreported pedigree with PACD, light and electron microscopic examination of an excised corneal button, genomewide linkage analysis, fine mapping linkage and haplotype analysis, and screening of four candidate genes (KERA, LUM, DCN, and EPYC). RESULTS: Twenty-one participants were determined to be affected based on the presence of characteristic clinical features of PACD; 15 affected and 39 unaffected individuals from a single pedigree enrolled in the study and provided DNA for analysis. Histopathologic examination of an excised corneal specimen from an affected individual demonstrated disorganized stromal lamellae and stromal staining with colloidal iron. Genomewide analysis demonstrated significant evidence of linkage to chromosome region 12q21.33 and evidence suggestive of linkage to chromosome region 8q22.3. Fine mapping of the chromosome 12 locus confirmed significant linkage; the largest multipoint log odds ratio score was 5.6 at D12S351. The linkage support interval was approximately 3.5 Mb (3.5 cM) in length between flanking markers D12S1812 and D12S95, roughly the entire chromosome band 12q21.33. No coding region mutations were identified in four candidate genes KERA, LUM, DCN, EPYC-located in the chromosome 12 linkage support interval. CONCLUSIONS: Linkage and haplotype analyses identified 12q21.33 as a locus for PACD. However, no mutations were identified in the candidate genes (KERA, LUM, DCN, EPYC) within this region. PMID- 20357200 TI - The cellular expression of antiangiogenic factors in fetal primate macula. AB - PURPOSE: To characterize the cellular expression patterns of antiangiogenic factors differentially regulated in the fetal human macula. METHODS: RNA was extracted from macular, nasal, and surround biopsies of three human fetal retinas at midgestation. Relative levels of expression of pigment epithelium-derived factor (PEDF), brain natriuretic peptide (BNP), collagen type IValpha2 (COL4A2), and natriuretic peptide receptors A and C (NPRA and NPRC) were determined with quantitative PCR. Cellular expression of PEDF and BNP was investigated by in situ hybridization on retinal sections from monkeys aged between fetal day 55 and 11 years. BNP, COL4A2, and NPRA proteins were localized by immunohistochemistry. Labeling was imaged and quantified by confocal microscopy and optical densitometry. RESULTS: Quantitative PCR confirmed higher levels of PEDF and BNP and lower levels of COL4A2 in the macula at midgestation. PEDF mRNA was detected in ganglion cells (GCs) and the pigment epithelium (RPE). BNP mRNA was detected in GCs and macroglia, although BNP immunoreactivity (IR) was predominantly perivascular. COL4A2-IR was detected in large blood vessels and NPRA-IR on the retinal vascular endothelium, GC axons in fetal retinas, and cone axons at all ages. Optical densitometry showed a graded expression of PEDF and BNP at all ages, with highest levels of expression in GCs in the developing fovea. CONCLUSIONS: Because the retinal vessels initially form in the GC layer, it is likely that PEDF has a key role in defining and maintaining the foveal avascular area. The precise role of BNP is unclear, but it may include both antiangiogenic and natriuretic functions. PMID- 20357202 TI - Regional macular light sensitivity changes in myopic Chinese adults: an MP1 study. AB - PURPOSE: To investigate the variation of macular light sensitivity (MLS) in myopic Chinese adults by using microperimetry. METHODS: MLS was recorded with the MP1 microperimeter (Nidek Technologies, Padova, Italy) in eyes affected by various degrees of myopia. Subjects were divided into group A (18-30 years) and group B (31-60 years). Subjects in both age groups were further divided based on refractive status: (1) high myopia (spherical equivalent, SE<-6.00 D); (2) low to moderate myopia (-6.00 DA; rs1800629) in TNF demonstrated a significant association with HTG (P = 0.012). The allele G frequency was higher in HTG patients than in control subjects (94.6% vs. 90.3%; OR = 1.89). One haplotype consisting of rs1799724 and rs1800629 was significantly associated with HTG (P = 0.015, corrected P = 0.045). One SNP (R72P; rs1042522) in TP53 was significantly associated with NTG (P = 0.018). The allele G frequency was higher in NTG patients than in control subjects (56.1% vs. 45.8%; OR = 1.52). The significance of these associations survived the Bonferroni correction (corrected P < 0.024). Other gene variants were not significantly associated with HTG (P > 0.063) or NTG (P > 0.13). None of the studied variants was significantly associated with JOAG (P > 0.17). CONCLUSIONS: The findings suggest that variants in TNF and TP53 are risk factors for POAG, whereas variants in other studied genes are not major risk factors for POAG, at least in the Chinese population. PMID- 20357203 TI - Absolute quantification of oxygenated hemoglobin within the visual cortex with functional near infrared spectroscopy (fNIRS). AB - PURPOSE: To examine absolute changes in oxygenated (HbO) and deoxygenated (Hb) hemoglobin concentrations over the visual cortex in response to visual stimulation. Before this study, only relative changes have been reported at the visual cortex. METHODS: Near infrared spectroscopy (NIRS) can be used to assess changes in hemoglobin concentration in tissue. A frequency domain oximeter with a specially designed probe was placed over the visual cortex while the participant viewed a checkerboard stimulus. The stimulus was alternated at 7.5 Hz for 30 seconds before being replaced by a control gray screen. RESULTS: The mean HbO concentration when the stimulus was presented was 26.8+/-3.9 microM, as opposed to 25.9+/-3.9 microM for the control condition, and the mean Hb concentration was 18.8+/-2.3 microM during stimulation and 19.1+/-2.3 microM during the control condition. The greatest change in HbO concentration occurred within the first 10 seconds. It did not increase significantly (P>0.01) after that time. CONCLUSIONS: This study is the first to demonstrate absolute quantification of HbO and Hb concentrations in the visual cortex with functional changes in hemoglobin concentrations in response to a visual stimulus. NIRS has the potential to be a valuable clinical tool in assessing the hemodynamics of the visual system in a quantitative and localized manner. PMID- 20357204 TI - Lattice corneal dystrophy type IV (p.Leu527Arg) is caused by a founder mutation of the TGFBI gene in a single Japanese ancestor. AB - PURPOSE: Lattice corneal dystrophy (LCD) type IV (LCD4) is a late-onset corneal dystrophy with amyloid deposition at the deep stromal layer of cornea. As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, beta-induced (TGFBI) gene. Although LCD type I has been reported worldwide, LCD4 has been reported only in the Japanese population. In the present study, a haplotype analysis was performed to investigate whether this LCD subtype is caused by a founder mutation. METHODS: Genomic DNA samples were extracted from 13 unrelated patients with LCD4. As a control, genomic DNA samples from 96 normal volunteers were also analyzed. For the haplotype analysis, the samples were amplified by polymerase chain reaction (PCR), TA-cloned, isothermally amplified, and subjected to a 1-base primer extension assay against a mutation site (c.1580T>G) and six known single nucleotide polymorphisms (SNPs; rs4669, rs2072239, rs7727725, rs17689879, rs6871571, and rs3792900), which are located adjacent to the mutation site. RESULTS: The haplotype analysis revealed that all the disease-carrying alleles from the 13 LCD4 patients shared an identical haplotype, whereas non-disease carrying alleles from the normal volunteers and the LCD4 patients exhibited four haplotypes. There was a statistically significant difference in the haplotype distribution between the disease-carrying and the non-disease-carrying alleles. CONCLUSIONS: The findings of this study strongly indicate that LCD4 was caused by a founder mutation of the TGFBI gene that occurred in a single Japanese ancestor. PMID- 20357206 TI - Macular thickness variations with sex, age, and axial length in healthy subjects: a spectral domain-optical coherence tomography study. AB - PURPOSE: To assess the relationship between macular retinal thickness and volume and age, sex, and refractive error/axial length with spectral domain-optical coherence tomography (SD-OCT). METHODS: One randomly selected eye of 198 consecutive ophthalmically normal subjects (104 men, 94 women) between July 2008 and January 2009, with corrected visual acuities better than 20/30 were included in this cross-sectional study. Complete ophthalmic examination, axial length measurement with a laser interferometer, and macular cube 512 x 128 scan by SD OCT were performed. RESULTS: The mean age was 55.6 +/- 16.4 years (range, 17-83), average refractive error was -2.17 +/- 4.82 (range, -23.50-3.75), and average axial length was 24.73 +/- 1.98 mm (range, 21.52-32.51). The central subfield thickness, average inner macular thickness, and overall macular volume were significantly lower in the female subjects (partial correlation: P = 0.009, P = 0.027, and P = 0.042, respectively). As age increased, average inner macular thickness, average outer macular thickness, overall average macular thickness, and macular volume decreased significantly (partial correlation: P = 0.002, P = 0.002, P = 0.002, and P = 0.000, respectively). Refractive error had no significant influence in partial correlation analysis. Axial length correlated negatively with average outer macular thickness, overall average macular thickness, and macular volume (partial correlation: P = 0.006, P = 0.044, and P = 0.003, respectively). CONCLUSIONS: In normal subjects, SD-OCT showed that retinal thickness is related to age, sex, and axial length, with regional variations. PMID- 20357205 TI - Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients. AB - PURPOSE: To determine mitochondrial (mt)DNA variants in AMD and age-matched normal retinas. METHODS: Total DNA was isolated from retinas (AMD, n = 13; age matched normal, n = 13), choroid (AMD, n = 3), and blood (AMD, n = 138; normal, n = 133). Long-extension-polymerase chain reaction amplified the full-length ( approximately 16.2 kb) mtDNA genome. Retinal mtDNA was sequenced for nucleotide variants and length heteroplasmy. Pyrosequencing was performed on heteroplasmic mtDNA. PCR amplification and enzyme digestions were used to analyze for nucleotide changes. RESULTS: Retinal mtDNA had a greater number of rearrangements and deletions than did blood mtDNA in normal samples (9.3 +/- 1.78 vs. 3 +/- 1.18, P = 0.019), and AMD samples (14.33 +/- 1.96 vs. 5.2 +/- 0.80, P = 0.0031. Five (55%) of 9 AMD patients had unreported SNPs, and 2 (16.6%) of 12 of the normal group did. The mtDNA coding region had 20 SNPs that produced amino acid changes. The noncoding MT-Dloop region had nucleotide heteroplasmy and length heteroplasmy. There were more SNPs per person in the AMD population than in the older (P = 0.003) and younger (P = 0.05) normal subjects. The C12557T (T-I) in the MT-ND5 gene was present in two AMD subjects (2/138) but was absent in the normal (0/133). Common mutations for Leber's hereditary optic neuropathy (LHON: G11778A; T14484C; and G3460A) were not present in AMD samples. CONCLUSIONS: AMD subjects have high levels of large mtDNA deletions/rearrangements in the retinas, unreported and amino acid-changing SNPs in the coding genome, and a greater number of SNPs per person in the noncoding MT-Dloop region. These mtDNA variants could diminish energy production efficiency, alter the mtDNA copy numbers and/or impact transcription in AMD retinas. PMID- 20357207 TI - Quantitative analysis of the effects of extracellular matrix proteins on membrane dynamics associated with corneal epithelial cell motility. AB - PURPOSE: Interaction of corneal epithelial cells with components of the basement membrane regulates cell morphology, adhesion, and migration. The authors examined the effects of basement membrane components on the behavior of human corneal epithelial (HCE) cells, including movement of the cell membrane in relation to the direction of cell migration. METHODS: HCE cells were plated on fibronectin, laminin, collagen types I and IV, and bovine serum albumin (BSA). Cell adhesion was evaluated by staining with crystal violet. Cell movement was monitored by time-lapse microscopy, and an image processing program was developed for quantitative analysis of movement of the cell membrane in relation to the direction of cell migration. Actin cytoskeleton, focal adhesions, and the K+ channel Kv2.1 were detected by fluorescence microscopy. RESULTS: Laminin, fibronectin, and collagen types I and IV each promoted cell adhesion compared with that apparent with BSA. Fibronectin and collagen types I and IV, but not laminin, increased cell motility. Laminin had no effect on membrane movement compared with that observed in the presence of BSA. Collagen types I and IV each increased membrane movement but in a manner independent of the direction of cell migration. Fibronectin induced membrane movement in the direction of cell migration. Fibronectin induced the formation of thick bundles of F-actin and focal adhesions at the cell periphery and the localization of Kv2.1 at the leading edge of the cell, whereas laminin and collagen types I and IV elicited the formation of thinner bundles of F-actin and smaller focal adhesions. CONCLUSIONS: Fibronectin may modulate the directional migration of corneal epithelial cells. PMID- 20357208 TI - Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor. AB - Glucocorticoids, major end effectors of the stress response, play an essential role in the homeostasis of the central nervous system (CNS) and contribute to memory consolidation and emotional control through their intracellular receptors, the glucocorticoid and mineralocorticoid receptors. Cyclin-dependent kinase 5 (CDK5), on the other hand, plays important roles in the morphogenesis and functions of the central nervous system, and its aberrant activation has been associated with development of neurodegenerative disorders. We previously reported that CDK5 phosphorylated the glucocorticoid receptor and modulated its transcriptional activity. Here we found that CDK5 also regulated mineralocorticoid receptor-induced transcriptional activity by phosphorylating multiple serine and threonine residues located in its N-terminal domain through physical interaction. Aldosterone and dexamethasone, respectively, increased and suppressed mRNA/protein expression of brain-derived neurotrophic factor (BDNF) in rat cortical neuronal cells, whereas the endogenous glucocorticoid corticosterone showed a biphasic effect. CDK5 enhanced the effect of aldosterone and dexamethasone on BDNF expression. Because this neurotrophic factor plays critical roles in neuronal viability, synaptic plasticity, consolidation of memory, and emotional changes, we suggest that aberrant activation of CDK5 might influence these functions through corticosteroid receptors/BDNF. PMID- 20357210 TI - False-positive IgM serology in coccidioidomycosis. AB - The clinical observation has been made that there might be an unacceptable number of false-positive enzyme immunoassay (EIA) test results for IgM among persons suspected of having coccidioidomycosis. Patients with a positive result for IgM by EIA are thought to have a diagnosis of acute coccidioidomycosis. However, this study found that 82% of patients with an IgM-positive and IgG-negative EIA result did not have coccidioidomycosis. PMID- 20357211 TI - Streptococcus gallolyticus subspecies pasteurianus (biotype II/2), a newly reported cause of adult meningitis. AB - We report the first case of adult meningitis confirmed to be due to Streptococcus gallolyticus subsp. pasteurianus. Phenotypically reported as Streptococcus bovis biotype II/2, 16S rRNA sequencing revealed S. gallolyticus subsp. pasteurianus. Because of taxonomic uncertainties, S. gallolyticus subsp. pasteurianus may be an underrecognized agent of systemic infections. PMID- 20357212 TI - Multicenter evaluation of a new shortened peptide nucleic acid fluorescence in situ hybridization procedure for species identification of select Gram-negative bacilli from blood cultures. AB - A shortened protocol for two peptide nucleic acid fluorescence in situ hybridization (PNA FISH) assays for the detection of Gram-negative bacilli from positive blood cultures was evaluated in a multicenter trial. There was 100% concordance between the two protocols for each assay (368 of 368 and 370 of 370 results) and 99.7% (367 of 368 and 369 of 370 results) agreement with routine laboratory techniques. PMID- 20357213 TI - Evaluation of new rapid antigen test for detection of pandemic influenza A/H1N1 2009 virus. AB - We evaluated the SD Bioline Influenza Ag A/B/A(H1N1) Pandemic test kit and compared it with real-time reverse transcriptase PCR (RT-PCR) for its ability to detect H1N1 2009. The sensitivity and specificity of the test kit for H1N1 2009 were 77% and 100%, respectively. PMID- 20357214 TI - Caspofungin: cross-reactivity in the Aspergillus antigen assay. PMID- 20357209 TI - Molecular genetic studies of gene identification for osteoporosis: the 2009 update. AB - Osteoporosis is a complex human disease that results in increased susceptibility to fragility fractures. It can be phenotypically characterized using several traits, including bone mineral density, bone size, bone strength, and bone turnover markers. The identification of gene variants that contribute to osteoporosis phenotypes, or responses to therapy, can eventually help individualize the prognosis, treatment, and prevention of fractures and their adverse outcomes. Our previously published reviews have comprehensively summarized the progress of molecular genetic studies of gene identification for osteoporosis and have covered the data available to the end of September 2007. This review represents our continuing efforts to summarize the important and representative findings published between October 2007 and November 2009. The topics covered include genetic association and linkage studies in humans, transgenic and knockout mouse models, as well as gene-expression microarray and proteomics studies. Major results are tabulated for comparison and ease of reference. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis. PMID- 20357215 TI - Comparison of the Luminex Respiratory Virus Panel fast assay with in-house real time PCR for respiratory viral infection diagnosis. AB - The Luminex xTAG Respiratory Virus Panel (RVP) assay has been shown to offer improved diagnostic sensitivity over traditional viral culture methods and to have a sensitivity comparable to those of individual real-time nucleic acid tests for respiratory viruses. The objective of this retrospective study was to test a new, streamlined version of this assay, the RVP Fast assay, which requires considerably less run time and operator involvement. The study compared the performance of the RVP Fast assay with those of viral culture, a direct fluorescent assay (DFA), and a panel of single and multiplex real-time PCRs in the testing of 286 respiratory specimens submitted to the Edinburgh Specialist Virology Centre for routine diagnosis of viral infection between December 2007 and February 2009. At least one respiratory viral infection was detected in 13.6% of specimens by culture and DFA combined, in 49.7% by real-time PCR, and in 46.2% by the RVP Fast assay. The sensitivity and specificity of the RVP Fast assay compared to the results of real-time PCR as the gold standard were 78.8% and 99.6%, respectively. Real-time PCR-positive specimens missed by the RVP Fast assay generally had low viral loads or were positive for adenovirus. Additionally, a small number of specimens were positive by the RVP Fast assay but were not detected by real-time PCR. For some viral targets, only a small number of positive results were found in our sample set using either method; therefore, the sensitivity of detection of the RVP Fast assay for individual targets could be investigated further with a greater number of virus-positive specimens. PMID- 20357216 TI - Legionella feeleii serotype 2 pneumonia in a man with chronic lymphocytic leukemia: a challenging diagnosis. AB - Legionella feeleii has rarely been reported as causing pneumonia in patients with hematologic malignancies. We present a case of Legionella feeleii serotype 2 pneumonia with empyema in a man with chronic lymphocytic leukemia and describe the methods of identifying this organism using both standard methods and newer diagnostic techniques. PMID- 20357217 TI - Emergence of vanB Enterococcus gallinarum colonization in association with glycopeptide therapy. PMID- 20357219 TI - Ag43 promotes persistence of uropathogenic Escherichia coli isolates in the urinary tract. PMID- 20357218 TI - Species recognition and clinical relevance of the zygomycetous genus Lichtheimia (syn. Absidia pro parte, Mycocladus). AB - The zygomycete genus Lichtheimia (syn. Absidia pro parte, Mycocladus) consists of saprotrophic fungi inhabiting soil or dead plant material. Lichtheimia corymbifera (syn. Absidia corymbifera, Mycocladus corymbifer) and Lichtheimia ramosa (syn. Absidia ramosa, Mycocladus ramosus) may cause fulminant infections in patients with impaired immunity. The present study investigated the species boundaries in Lichtheimia using genealogical concordance phylogenetic species recognition (by comparison of the genealogies of the internal transcribed spacer [ITS] sequence, the D1/D2 region of the large subunit [LSU], and actin), biological species recognition by mating tests, as well as morphological and physiological characteristics. The three molecular markers used were selected by evaluating the polymorphisms and paralogies of several loci, including those for beta-tubulin, translation elongation factor 1alpha, the two largest subunits of the RNA polymerase II (RPB1 and RPB2), the mitochondrial cytochrome c oxidase subunit I (COI), and the mitochondrial small-subunit (mtSSU) rDNA, among four strains belonging to different putative species. Comparing the genealogies of the ITS, LSU, and actin genes, we recognized seven phylogenetic species. However, mating tests did not show intrinsic reproductive barriers for two pairs of the phylogenetic species. Therefore, we regard five species in Lichtheima to be confirmed: Lichtheimia corymbifera, L. ornata comb. nov., L. ramosa, L. hyalospora, and L. sphaerocystis sp. nov. Only the first three species seem to have clinical relevance. Lichtheimia blakesleeana is reduced to a synonym of Lichtheimia hyalospora. We provide a detailed description of Lichtheimia sphaerocystis sp. nov. and a key for the identification of all accepted species identified in the present study on the basis of their morphological traits and growth at different temperatures. PMID- 20357220 TI - Chlamydia trachomatis serovar distribution and Neisseria gonorrhoeae coinfection in male patients with urethritis in Greece. AB - The distribution of Chlamydia trachomatis serovars and Neisseria gonorrhoeae coinfection was studied in a group of 100 C. trachomatis-positive males with urethritis in Greece. The serovar distribution revealed that apart from the predominant worldwide types E and F, the relatively uncommon type G is also prevalent. Gonococcal coinfection was frequent (30%) and was associated with genovariant Ja (75%, P = 0.008). PMID- 20357221 TI - New therapeutic and biomarker discovery for peripheral diabetic neuropathy: PARP inhibitor, nitrotyrosine, and tumor necrosis factor-{alpha}. AB - This study evaluated poly(ADP-ribose) polymerase (PARP) inhibition as a new therapeutic approach for peripheral diabetic neuropathy using clinically relevant animal model and endpoints, and nitrotyrosine (NT), TNF-alpha, and nitrite/nitrate as potential biomarkers of the disease. Control and streptozotocin-diabetic rats were maintained with or without treatment with orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2 diaza-benzo[de]anthracen-3-one (GPI-15,427), 30 mg kg(-1) d(-1), for 10 wk after first 2 wk without treatment. Therapeutic efficacy was evaluated by poly(ADP ribosyl)ated protein expression (Western blot analysis), motor and sensory nerve conduction velocities, and tibial nerve morphometry. Sciatic nerve and spinal cord NT, TNF-alpha, and nitrite/nitrate concentrations were measured by ELISA. NT localization in peripheral nervous system was evaluated by double-label fluorescent immunohistochemistry. A PARP inhibitor treatment counteracted diabetes-induced motor and sensory nerve conduction slowing, axonal atrophy of large myelinated fibers, and increase in sciatic nerve and spinal cord NT and TNF alpha concentrations. Sciatic nerve NT and TNF-alpha concentrations inversely correlated with motor and sensory nerve conduction velocities and myelin thickness, whereas nitrite/nitrate concentrations were indistinguishable between control and diabetic groups. NT accumulation was identified in endothelial and Schwann cells of the peripheral nerve, neurons, astrocytes, and oligodendrocytes of the spinal cord, and neurons and glial cells of the dorsal root ganglia. The findings identify PARP as a compelling drug target for prevention and treatment of both functional and structural manifestations of peripheral diabetic neuropathy and provide rationale for detailed evaluation of NT and TNF-alpha as potential biomarkers of its presence, severity, and progression. PMID- 20357222 TI - Gonadotropins regulate rat testicular tight junctions in vivo. AB - Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n = 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonadotropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immunostaining. Short-term hormone replacement stimulated significant recoveries in adluminal germ cell numbers. In hCG +/- FSH antibody-treated rats, occludin and claudin-11 protein relocalized at the TJ, but such relocalization was minimal with FSH alone. Tubule lumens also reappeared, but most tubules remained permeable to biotin tracer, despite the presence of occludin. It is concluded that gonadotropins maintain Sertoli cell TJs in the adult rat via a mechanism that includes the localization of occludin and claudin-11 at functional TJs. PMID- 20357223 TI - Identification of a novel role for endothelins within the oviduct. AB - Endothelins were first identified as potent vasoactive peptides; however, diversity in the biological function of these hormones is now evident. We have identified a novel role for endothelins: a requirement for these peptides within the oviduct during fertilization and/or early embryo development. In vivo, treatment after ovulation with a dual endothelin receptor antagonist (tezosentan) decreased the number of two-cell embryos that could be collected from within the oviducts. In vitro fertilization experiments showed that gamete viability and their ability to fertilize were not affected by treatment with this antagonist, suggesting that the effect observed in vivo was mediated by the oviduct itself. Expression of mRNA for all three isoforms of the endothelins and both receptor subtypes was detectable within the oviduct. Expression of mRNA for endothelin-3 was regulated by gonadotropins in epithelial cells of the oviduct and increased specifically within the isthmus of this structure. Immunostaining revealed localization of both endothelin receptors A and B to the columnar epithelial cells within the oviduct, suggestive of a local role for endothelins in the regulation of epithelial function and ultimately oviductal secretions. A microarray analysis revealed three likely endothelin-regulated protein networks for future analysis: the TGFbeta, IL-10, and CCAAT/enhancer-binding protein superfamilies. Overall, these results suggest a novel and requisite role for endothelins within the oviduct during fertilization and/or early embryo development. PMID- 20357227 TI - Sometimes the answer is asking the question. PMID- 20357224 TI - Runt-related transcription factors impair activin induction of the follicle stimulating hormone {beta}-subunit gene. AB - Synthesis of the FSH beta-subunit (FSHbeta) is critical for normal reproduction in mammals, and its expression within the pituitary gonadotrope is tightly regulated by activin. Here we show that Runt-related (RUNX) proteins, transcriptional regulators known to interact with TGFbeta signaling pathways, suppress activin induction of FSHbeta gene expression. Runx2 is expressed within the murine pituitary gland and dramatically represses activin-induced FSHbeta promoter activity, without affecting basal expression in LbetaT2 cells, an immortalized mouse gonadotrope cell line. This repressive effect is specific, because RUNX2 induces LHbeta transcription (with or without activin) and does not interfere with GnRH induction of either gonadotropin beta-subunit gene. Analysis of the murine FSHbeta promoter by transfection and gel shift assays reveals that RUNX2 repression localizes to a Runx-binding element at -159/-153, which is adjacent to a previously recognized region critical for activin induction. Mutation of this -153 activin-response element or, indeed, any of the five activin-responsive regions prevents activin induction and, in fact, RUNX2 suppression, instead converting RUNX2 to an activator of the FSHbeta gene. Although the Runx-binding element is required for RUNX2-mediated repression of FSHbeta induction by either activin or Smad3, confirming a functional role of this novel site, protein interactions in addition to those between RUNX2 and Smads are necessary to account for full repression of activin induction. In summary, the present study provides evidence for Runx2-mediated repression of activin-induced FSHbeta gene expression and reveals the context dependence of Runx2 action in hormonal regulation of the gonadotropin genes. PMID- 20357228 TI - Reporting and notification of adverse events in orthopaedics. AB - Surgeons should know how to alert the US FDA when an adverse event occurs with a device that has been approved by the FDA. Documentation of such events is critically important to help identify trends concerning a particular device, thereby helping surgeons and other health care professionals avoid similar events. The FDA created the MedWatch program to aid health care professionals in reporting adverse events. Orthopaedic surgeons can use the program to get up-to date alerts and help protect their patients. PMID- 20357225 TI - Interventions to improve patient comprehension in informed consent for medical and surgical procedures: a systematic review. AB - BACKGROUND: Patient understanding in clinical informed consent is often poor. Little is known about the effectiveness of interventions to improve comprehension or the extent to which such interventions address different elements of understanding in informed consent. PURPOSE: . To systematically review communication interventions to improve patient comprehension in informed consent for medical and surgical procedures. Data Sources. A systematic literature search of English-language articles in MEDLINE (1949-2008) and EMBASE (1974-2008) was performed. In addition, a published bibliography of empirical research on informed consent and the reference lists of all eligible studies were reviewed. Study Selection. Randomized controlled trials and controlled trials with nonrandom allocation were included if they compared comprehension in informed consent for a medical or surgical procedure. Only studies that used a quantitative, objective measure of understanding were included. All studies addressed informed consent for a needed or recommended procedure in actual patients. Data Extraction. Reviewers independently extracted data using a standardized form. All results were compared, and disagreements were resolved by consensus. Data Synthesis. Forty-four studies were eligible. Intervention categories included written information, audiovisual/multimedia, extended discussions, and test/feedback techniques. The majority of studies assessed patient understanding of procedural risks; other elements included benefits, alternatives, and general knowledge about the procedure. Only 6 of 44 studies assessed all 4 elements of understanding. Interventions were generally effective in improving patient comprehension, especially regarding risks and general knowledge. Limitations. Many studies failed to include adequate description of the study population, and outcome measures varied widely. CONCLUSIONS: . A wide range of communication interventions improve comprehension in clinical informed consent. Decisions to enhance informed consent should consider the importance of different elements of understanding, beyond procedural risks, as well as feasibility and acceptability of the intervention to clinicians and patients. Conceptual clarity regarding the key elements of informed consent knowledge will help to focus improvements and standardize evaluations. PMID- 20357229 TI - Hip dislocation: evaluation and management. AB - A simple hip dislocation is one without fracture of the proximal femur or acetabulum. Complex fracture-dislocations involve the acetabulum, femoral head, or femoral neck. The incidence of posttraumatic arthritis is much lower in simple dislocations than in fracture-dislocations. The most common mechanism of injury is a high-energy motor vehicle accident, which is usually associated with other systemic and musculoskeletal injuries. The hip should be reduced emergently in an atraumatic fashion. For acetabular fracture, intraoperative stress views may be necessary to evaluate for instability and to determine whether surgical fixation is required. The appearance of a concentric reduction on plain radiographs and CT does not rule out intra-articular hip pathology; such injury may contribute to long-term degenerative changes. Other complications of hip dislocation include osteoarthritis, osteonecrosis, and sciatic nerve injury. Indications for surgical management include nonconcentric reduction, associated proximal femur fracture (including hip, femoral neck, and femoral head), and associated acetabular fracture producing instability. Surgical management ranges from formal open arthrotomy to minimally invasive hip arthroscopy. Hip arthroscopy has become popular for treating intra-articular hip pathology, including loose bodies, chondral defects, and labral tears. PMID- 20357230 TI - Advances in the management of spinal cord injury. AB - Historically, clinical outcomes following spinal cord injury have been dismal. Over the past 20 years, the survival rate and long-term outcome of patients with spinal cord injury have improved with advances in both medical and surgical treatment. However, the efficacy and timing of these adjuvant treatments remain controversial. There has been a tremendous increase in the number of basic science and clinical studies on spinal cord injury. Current areas of investigation include early acute management, including early surgical intervention, as well as new pharmacotherapy and cellular transplantation strategies. It is unlikely that a single approach can uniformly address all of the issues associated with spinal cord injury. Thus, a multidisciplinary approach will be needed. PMID- 20357231 TI - Evolving techniques in foot and ankle amputation. AB - Multiple clinical pathways lead to lower extremity amputation, including trauma, dysvascular disease, congenital defects, and malignancy. However, the principles of successful amputation-careful preoperative planning, coordination of a multidisciplinary team, and good surgical technique-remain the same. Organized rehabilitation and properly selected prostheses are integral components of amputee care. In the civilian setting, amputation is usually performed as a planned therapy for an unsalvageable extremity, not as an emergency procedure. The partial loss of a lower limb often represents a major change in a person's life, but patients should be encouraged to approach amputation as the beginning of a new phase of life and not as the culmination of previous treatment failures. PMID- 20357232 TI - Scapulothoracic fusion. PMID- 20357238 TI - Safety, tolerability, and efficacy of high-frequency chest wall oscillation in pediatric patients with cerebral palsy and neuromuscular diseases: an exploratory randomized controlled trial. AB - Airway secretions and infections are common in cerebral palsy and neuromuscular diseases. Chest physiotherapy is standard therapy but effort is substantial. High frequency chest wall oscillation is used in cystic fibrosis but tolerability and safety data in cerebral palsy and neuromuscular disease are limited. A prospective, randomized, controlled trial of high-frequency chest wall oscillation and standard chest physiotherapy was performed in participants with neuromuscular disease or cerebral palsy. Outcome measures included respiratory related hospitalizations, antibiotic therapy, chest radiographs, and polysomnography. Care-givers were questioned regarding therapy adherence. A total of 28 participants enrolled, 23 completed (12 chest physiotherapy, mean study period 5 months). No adverse outcomes were reported. Adherence to prescribed regimen was higher with high-frequency chest wall oscillation (P = .036). Our data suggest safety, tolerability, and better compliance with high-frequency chest wall oscillation. Improvement in airway clearance may help prevent hospitalizations. Larger controlled trials are required to confirm these results. PMID- 20357237 TI - Incidence of papilledema and obesity in children diagnosed with idiopathic ''benign'' intracranial hypertension: case series and review. AB - Idiopathic intracranial hypertension is an important cause of headaches in the pediatric population and can lead to permanent blindness if not diagnosed in a timely manner. The aim of this study was to characterize the incidence of papilledema and obesity in children with idiopathic intracranial hypertension. We retrospectively analyzed 27 patients followed at The University of Texas Houston Pediatric Neurology Clinic. Papilledema was absent in 13 (48%) patients. The majority of our patients were nonobese (70%). Our results are contrary to the current medical practice of associating papilledema and obesity with idiopathic intracranial hypertension in childhood and highlight the importance of revised diagnostic criteria in this population needed to detect and manage this condition. PMID- 20357239 TI - Epidemiology and clinical spectrum of schizencephaly in south-eastern Hungary. AB - The epidemiology and clinical spectrum of schizencephaly in south-eastern Hungary have been surveyed in a retrospective population-based study. A total of 10 patients (6 boys and 4 girls) were found with schizencephaly among 185 486 live births in a period of 14 years (July 1, 1992 to June 30, 2006), which means a birth prevalence of 0.54 per 10 000 (95% confidence interval [CI]: 0.20-0.87). The schizencephaly was unilateral in 7 cases (with closed lips in 5 and open lips in 2 patients) and bilateral in 3 children (with closed lips in 2 and open lips in 1). The septum pellucidum was absent in 5 cases; however, optic nerve hypoplasia was not found in these patients. Delayed development and intellectual disability were observed in all patients, except 2 with unilateral closed lip schizencephaly. Epilepsy was diagnosed in 3 patients (2 with unilateral and 1 with bilateral schizencephaly). PMID- 20357240 TI - Maternal methylenetetrahydrofolate reductase (MTHFR) homozygosity and neonatal outcome: follow-up of 42 pregnancies at risk. AB - From February 2006 to March 2008, 42 pregnant women homozygous for the 677CT methylenetetrahydrofolate reductase (MTHFR) allele were recruited in our obstetrics service for pregnancy at risk. All had antithrombotic prophylaxis with low-dose aspirin and/or low-molecular-weight heparin, supplemented with folic acid. In all, 2 women lost the fetus and 4 were lost to follow-up before delivery. A total of 36 women delivered term infants who all underwent transfontanellar ultrasonography within 24 hours of birth. Six (16.6%) had ischemic or hemorrhagic cerebral lesions. No differences were observed in gestational age, birth weight, or umbilical cord pH between the 30 healthy infants and the 6 with cerebral lesions. Neonatal outcomes were negative in spite of maternal folic acid supplementation and antithrombotic prophylaxis during pregnancy. This suggests a relationship between maternal homozygous mutation in the 677CT-MTHFR allele and neonatal cerebral lesions. PMID- 20357241 TI - Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development. AB - The generation of natural regulatory T cells (nTregs) is crucial for the establishment of immunologic self-tolerance and the prevention of autoimmunity. Still, the origin of nTregs and the mechanisms governing their differentiation within the thymus are poorly understood, particularly in humans. It was recently shown that conventional dendritic cells (cDCs) in human thymus were capable of inducing nTreg differentiation. However, the function of plasmacytoid DCs (pDCs), the other major subset of thymic DCs, remains unknown. Here we report that pDCs resident in the human thymus, when activated with CD40 ligand (CD40L) plus interleukin-3, efficiently promoted the generation of CD4(+)CD25(+)Foxp3(+) nTregs from autologous thymocytes. The progenitors of these nTregs were selectively found within CD4(+)CD8(+) thymocytes that had accomplished positive selection, as judged by their CD69(hi)TCR(hi) phenotype. Supporting the involvement of the CD40-CD40L pathway in pDC-induced nTreg generation, we show that positively selected CD4(+)CD8(+) progenitors specifically transcribed CD40L in vivo and up-regulated CD40L expression on T-cell receptor engagement, thereby promoting the activation of pDCs. Finally, evidence is provided that nTregs primed by pDCs displayed reciprocal interleukin-10/transforming growth factor beta cytokine expression profiles compared with nTregs primed by cDCs. This functional diversity further supports a nonredundant tolerogenic role for thymic pDCs in the human thymus. PMID- 20357242 TI - Hematopoietic stem cell function requires 12/15-lipoxygenase-dependent fatty acid metabolism. AB - Fatty acid metabolism governs multiple intracellular signaling pathways in many cell types, but its role in hematopoietic stem cells (HSCs) is largely unknown. Herein, we establish a critical role for 12/15-lipoxygenase (12/15-LOX)-mediated unsaturated fatty acid metabolism in HSC function. HSCs from 12/15-LOX-deficient mice are severely compromised in their capacity to reconstitute the hematopoietic compartment in competitive and serial reconstitution assays. Furthermore, we demonstrate that 12/15-LOX is required for the maintenance of long-term HSC quiescence and number. The defect in HSCs is cell-autonomous and associated with a selective reduction in 12/15-LOX-mediated generation of bioactive lipid mediators and reactive oxygen species and with a decrease in canonical Wnt signaling as measured by nuclear beta-catenin staining. These results have implications for development, aging, and transformation of the hematopoietic compartment. PMID- 20357243 TI - The IgG-specific endoglycosidase EndoS inhibits both cellular and complement mediated autoimmune hemolysis. AB - EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human immunoglobulin G and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody-mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, ie, phagocytosis, complement activation, and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pretreatment of anti-D with EndoS before sensitization of RBCs and abrogated by direct addition of EndoS to blood containing sensitized RBCs. The toxic effects of monocytes stimulated with anti-D-sensitized RBCs, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBCs and complement-mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBCs was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC immunoglobulin G2a monoclonal autoantibody and complement activation and erythrophagocytosis by Kupffer cells in the liver were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody-mediated destruction of RBCs. PMID- 20357244 TI - Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro. AB - In the disorder leukocyte adhesion deficiency III (LAD-III), integrins on platelets and leukocytes are expressed but fail to function and this leads to severe bleeding and infections at an early age. Mutation in the KINDLIN3 (FERMT3) gene is the cause of LAD-III in patients from the Middle East, Malta, and Turkey. We describe 2 novel homozygous mutations in the KINDLIN3 gene of a new African American patient that destabilize KINDLIN3 mRNA leading to loss of kindlin-3 protein. Transfection of wild-type (WT) KINDLIN3 cDNA restored integrin-related adhesion and migration in the LAD-III patient's T and B lymphocytes. We analyzed the individual mutations separately in vitro to learn more about the function of the kindlin-3 protein. The first G>A mutation gives rise to a Gly308Arg change at the end of FERM (protein 4.1, ezrin, radixin, moesin) subdomain 2, and the second mutation is a base deletion causing early termination within the pleckstrin homology (PH) domain. This second mutation prevented membrane association of kindlin-3 and did not restore either adhesion or migration, whereas the FERM subdomain 2 mutation affected only migration. Thus, these LAD-III patient mutations have highlighted functionally important regions of kindlin-3 that alter leukocyte integrin-dependent function in 2 distinct ways. PMID- 20357246 TI - Racial disparities in outcomes of colorectal cancer screening: biology or barriers to optimal care? PMID- 20357245 TI - Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities. AB - BACKGROUND: It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility. METHODS: A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race. RESULTS: Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas <10 mm), or colorectal cancer. CONCLUSIONS: We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology. PMID- 20357247 TI - How well can MRI predict MS in children with acute disseminated encephalomyelitis? PMID- 20357248 TI - Intron-containing type I and type III IFN coexist in amphibians: refuting the concept that a retroposition event gave rise to type I IFNs. AB - Type I and III IFNs are structurally related cytokines with similar antiviral functions. They have different genomic organizations and bind to distinct receptor complexes. It has been vigorously debated whether the recently identified intron containing IFN genes in fish and amphibians belong to the type I or III IFN family or diverged from a common ancestral gene, that subsequently gave rise to both types. In this report, we have identified intron containing type III IFN genes that are tandemly linked in the Xenopus tropicalis genome and hence demonstrate for the first time that intron containing type I and III genes diverged relatively early in vertebrate evolution, and at least by the appearance of early tetrapods, a transition period when vertebrates migrated from an aquatic environment to land. Our data also suggest that the intronless type I IFN genes seen in reptiles, birds, and mammals have originated from a type I IFN transcript via a retroposition event that led to the disappearance of intron-containing type I IFN genes in modern vertebrates. In vivo and in vitro studies in this paper show that the Xenopus type III IFNs and their cognate receptor are ubiquitously expressed in tissues and primary splenocytes and can be upregulated by stimulation with synthetic double-stranded RNA, suggesting they are involved in antiviral defense in amphibians. PMID- 20357249 TI - CXC chemokine ligand 2 induced by receptor activator of NF-kappa B ligand enhances osteoclastogenesis. AB - CXCL2 has been known to regulate immune functions mainly by chemo-attracting neutrophils. In this study, we show that CXCL2 can be induced by receptor activator of NF-kappaB ligand, the osteoclast (OC) differentiation factor, through JNK and NF-kappaB signaling pathways in OC precursor cells. CXCL2 in turn enhanced the proliferation of OC precursor cells of bone marrow-derived macrophages (BMMs) through the activation of ERK. Knockdown of CXCL2 inhibited both the proliferation of and the ERK activation in BMMs. During osteoclastogenesis CXCL2 stimulated the adhesion and the migration of BMMs. Moreover, the formation of OCs from BMMs was significantly increased on treatment with CXCL2. Conversely, the CXCL2 antagonist repertaxin and a CXCL2 neutralizing Ab potently reduced receptor activator of NF-kappaB ligand-induced osteoclastogenesis. Furthermore, CXCL2 evoked fulminant bone erosion in the in vivo mouse experiments. Finally, prominent upregulation of CXCL2 was detected in synovial fluids and sera from rheumatoid arthritis patients, suggesting a potential involvement of CXCL2-mediated osteoclastogenesis in rheumatoid arthritis-associated bone destruction. Thus, CXCL2 is a novel therapeutic target for inflammatory bone destructive diseases. PMID- 20357250 TI - TLR4 promotes B cell maturation: independence and cooperation with B lymphocyte activating factor. AB - We have previously shown that TLR4 triggering promotes the generation of CD23(+)CD93(+) transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23(+) transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF. For both BAFF and LPS, functional maturation of the IgM(+)CD23(+)CD93(+) cells was confirmed by their higher proliferative response to anti-CD40 plus IL-4 compared with IgM(+)CD23(neg)CD93(+) cells. BAFF R-Fc-mediated neutralization experiments showed that TLR4-induced B cell maturation was independent of BAFF. Distinct from BAFF, maturation by LPS relied on the activation of canonical NF-kappaB pathway, and the two factors together had complementary effects, leading to higher numbers of IgM(+)CD23(+)CD93(+) cells with their simultaneous addition. Importantly, BCR cross-linking abrogated the generation of CD23(+) B cells by LPS or BAFF, indicating that signals mimicking central tolerance act on both systems. Addition of cyclosporin A reverted BCR-mediated inhibition, both for BAFF and LPS, suggesting similar regulation of signaling pathways by calcineurin. Finally, LPS-injected mice showed a rapid increase of mature B cells in the bone marrow, suggesting that TLR4 signaling may effectively stimulate B cell maturation in vivo, acting as an accessory stimulus in B cell development, complementary to the BAFF physiological pathway. PMID- 20357251 TI - At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells. AB - Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil(+), as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil(+) compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10-producing aTreg/Tr1s in Fil(+). Together, these data show that at steady state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level. PMID- 20357252 TI - The role of skin-derived dendritic cells in CD8+ T cell priming following immunization with lentivectors. AB - Although skin dendritic cells (DCs) have been shown to directly present Ag to CD8(+) T cells after intradermal immunization with lentivectors, the contribution of the different skin DC subsets to this process remains unclear. Using langerin diphtheria toxin receptor transgenic mice we demonstrated that ablation of langerhans cells and langerin-expressing positive dermal DCs (Ln(+)dDCs) did not interfere with the generation of CD8(+) T cells by lentiviral vectors. Consistent with these findings, the absence of langerhans cells and Ln(+)dDCs did not hamper the presentation level of lentiviral-derived Ag by skin DCs in vitro. We further demonstrated that only dDCs and Ln(+)dDCs were capable of presenting Ag, however, the number of dDCs migrating to the draining lymph nodes was 6-fold higher than that of Ln(+)dDCs. To study how the duration of DC migration influences CD8(+) T cell responses, we analyzed the kinetics of Ag expression at the injection site and manipulated DC migration by excising the injected skin at various times after immunization. A low level of Ag expression was seen 1 wk after the immunization; peaked during week 2, and was considerably cleared by week 3 via a perforin dependent fas-independent mechanism. Removing the injection site 3 or 5 d, but not 10 d, after the immunization, resulted in a reduced CD8(+) T cell response. These findings suggest that dDCs are the main APCs active after intradermal lentiviral-mediated immunization, and migration of dDCs in the initial 10-d period postimmunization is required for optimal CD8(+) T cell induction. PMID- 20357253 TI - Intragraft Th17 infiltrate promotes lymphoid neogenesis and hastens clinical chronic rejection. AB - To evaluate the influence of intragraft inflammatory infiltrate on the course of chronic rejection, 11 human renal grafts, detransplanted for terminal failure, were analyzed. Samples were divided into two groups according to their graft survival (> or < or = 8 y). In both groups, the main cell population infiltrating the graft interstitia was T lymphocytes. The extent of the lymphocytic infiltration and the distribution of naive and memory, CD4(+) and CD8(+) T cells, were similar in both groups. Although all types of Th polarization profiles can lead to terminal chronic rejection, a correlation between shorter graft survival and the presence of Th17 cells that produce IL-17 and IL-21 was observed. In contrast, grafts infiltrated by regulatory T cells survived significantly longer. The correlation between the expressions of activation-induced cytidine deaminase (the key enzyme of the germinal center reaction) and IL-21 suggests that Th17 could exert their deleterious effect by promoting lymphoid neogenesis, namely, the organization of inflammatory effectors into ectopic germinal centers in which a local humoral immune response is elicited. Further studies will determine whether Th17 infiltration can be used as a prognosis tool and whether the Th17 subset constitutes a therapeutic target for slowing down chronic rejection. PMID- 20357255 TI - Cutting edge: granulocyte-macrophage colony-stimulating factor is the major CD8+ T cell-derived licensing factor for dendritic cell activation. AB - During priming, CD8(+) T lymphocytes can induce robust maturation of dendritic cells (DCs) in a CD40-independent manner by secreting licensing factor(s). In this study, we isolate this so-far elusive licensing factor and identify it, surprisingly, as GM-CSF. This provides a new face for an old factor with a well known supporting role in DC development and recruitment. Signaling through the GM CSFR in ex vivo-purified DCs upregulated the expression of costimulatory molecules more efficiently than did any tested TLR agonist and provided a positive feedback loop in the stimulation of CD8(+) T cell proliferation. Combined with a variety of microbial stimuli, GM-CSF supports the formation of potent "effector" DCs capable of secreting a variety of proinflammatory cytokines that guide the differentiation of T cells during the immune response. PMID- 20357254 TI - Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins block distinct steps in transendothelial migration of effector memory CD4+ T cells by targeting different endothelial proteins. AB - ORFK3 (K3) and ORFK5 (K5) are Kaposi's sarcoma-associated herpesvirus-encoded E3 ubiquitin ligases that differentially reduce surface expression of various proteins in infected cells. In this study, we describe their effects on human dermal microvascular endothelial cells (ECs), a natural target of Kaposi's sarcoma-associated herpesvirus infection. TNF-treated human dermal microvascular ECs transduced to express K5 show reduced capacity to capture effector memory (EM) CD4+ T cells under conditions of venular shear stress. K5 but not K3 transduction significantly reduces ICAM-1 expression and the inhibition of T cell capture was phenocopied by small interfering RNA knockdown of ICAM-1 and by anti ICAM-1 Ab blocking. Cotransduction with an ICAM-1 truncated construct not subject to K5 ubiquitylation restored EM CD4+ T cell capture. K3 transductants effectively capture EM CD4+ T cells, but fail to support their transendothelial migration (TEM) in response to TCR engagement by superantigen presented by the ECs, leaving intact chemokine-dependent TEM. K3 but not K5 transduction significantly reduces PECAM-1 expression, and the effect on TCR-induced TEM is phenocopied by small interfering RNA knockdown of PECAM-1 and by anti-PECAM-1 Ab blocking. TCR-dependent TEM was restored in K3 transductants cotransduced to express a mutant of PECAM-1 not subject to K3-induced ubiquitylation. EM CD4+ T cells lack any known PECAM-1 counter receptor, but heterophilic engagement of PECAM-1 can involve glycosaminoglycans. In addition, TCR-induced TEM, but not chemokine-induced TEM, appears to involve a heparan- or chondroitin-like molecule on T cells. These results both identify specific roles of K5 and K3 in immune evasion and further differentiate the processes of inflammatory chemokine- versus TCR-dependent recruitment of human EM CD4+ T cells. PMID- 20357256 TI - Disordered lymphoid purine metabolism contributes to the pathogenesis of persistent Borrelia garinii infection in mice. AB - Extracellular ATP and adenosine are important regulators of immune responses; however, contribution of purinergic signaling to host defense during persistent microbial infections remains obscure. Lyme borreliosis is a common arthropod borne infection caused by Borrelia burgdorferi sensu lato. In this study, we investigated whether lymphoid purinergic signaling contributes to the mechanisms by which borreliae species evade the immune system and trigger joint inflammation. Intracutaneous inoculation of Borrelia garinii to C3H/He mice induced symptomatic infection manifested in elevated levels of borrelia-specific IgG Abs, persistent spirochete dissemination into the tissues and joint swelling, as well as approximately 2- to 2.5-fold enlargement of draining lymph nodes with hyperplasia of B cell follicle area and L-selectin shedding from activated T lymphocytes. Purine catabolism was also activated in lymph nodes but not spleen and blood of infected C3H/He mice within the first 4 postinfection weeks, particularly manifested in transient upregulations of adenosine triphosphatase/ectonucleoside triphosphate diphosphohydrolase and ecto-5' nucleotidase/CD73 on CD4(+)CD8(+) T lymphocytes and adenosine deaminase activity on B220(+) B lymphocytes. Compared with borrelia-susceptible C3H/He strain, lymphocytes from C57BL/6 mice displayed markedly enhanced adenosine-generating capability due to approximately three times higher ratio of ecto-5'-nucleotidase to adenosine deaminase. Borrelia-infected C57BL/6 mice efficiently eradicated the inoculated spirochetes at more chronic stage without any signs of arthritis. Strikingly, deletion of key adenosine-generating enzyme, ecto-5' nucleotidase/CD73, was accompanied by significantly enhanced joint swelling in borrelia-infected CD73-deficient C57BL/6 mice. Collectively, these data suggest that insufficient basal adenosine level and/or pathogen-induced disordered lymphoid purine homeostasis may serve as important prerequisite for promotion of inflammatory responses and further host's commitment to persistence of bacterial infection and arthritis development. PMID- 20357257 TI - Evolution of the pentraxin family: the new entry PTX4. AB - Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins, some of which are components of the humoral arm of innate immunity and behave as functional ancestors of Abs. They are divided into short (C-reactive protein and serum amyloid P component) and long pentraxins (PTX3 and neuronal pentraxins). Based on a search for pentraxin domain-containing sequences in databases, a phylogenetic analysis of the pentraxin family from mammals to arthropods was conducted. This effort resulted in the identification of a new long pentraxin (PTX4) conserved from mammals to lower vertebrates, which clusters alone in phylogenetic analysis. The results indicated that the pentraxins consist of five clusters: short pentraxins, which can be found in chordate and arthropods; neuronal pentraxins; the prototypic long pentraxin PTX3, which originated very early at the divergence of the vertebrates; the Drosophila pentraxin-like protein B6; and the long pentraxin PTX4 discovered in this study. Conservation of flanking genes in mammalian evolution indicates maintenance of synteny. Analysis of PTX4, in silico and by transcript expression, shows that the gene is well conserved from mammals to lower vertebrates and has a unique pattern of mRNA expression. Thus, PTX4 is a new unique member of the pentraxin superfamily, conserved in evolution. PMID- 20357258 TI - IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes. AB - Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17-producing CD4(+) T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17(+) T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17(+) T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-gamma(+)IL 17(+)) and Th0/IL-17 (IFN-gamma(+)IL-17(+)IL-4(+)) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-gamma-dominated ACD environment, IL-17 releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL 6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL 17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte-T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-gamma and IL-17 rendered keratinocytes susceptible to ICAM-1-dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage. PMID- 20357259 TI - B cells have distinct roles in host protection against different nematode parasites. AB - B cells can mediate protective responses against nematode parasites by supporting Th2 cell development and/or by producing Abs. To examine this, B cell-deficient mice were inoculated with Nippostrongylus brasiliensis or Heligmosomoides polygyrus. B cell-deficient and wild type mice showed similar elevations in Th2 cytokines and worm expulsion after N. brasiliensis inoculation. Worm expulsion was inhibited in H. polygyrus-inoculated B cell-deficient mice, although Th2 cytokine elevations in mucosal tissues were unaffected. Impaired larval migration and development was compromised as early as day 4 after H. polygyrus challenge, and administration of immune serum restored protective immunity in B cell deficient mice, indicating a primary role for Ab. Immune serum even mediated protective effects when administered to naive mice prior to inoculation. This study suggests variability in the importance of B cells in mediating protection against intestinal nematode parasites, and it indicates an important role for Ab in resistance to tissue-dwelling parasites. PMID- 20357261 TI - Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. AB - Random V(D)J junctions ensure that the diversity of the Ig primary repertoire is adapted to the vast heterogeneity of Ags. In two-thirds of cases, recombination between variable segments induces a frameshift in the open reading frame and generates a premature termination codon. In B cells harboring biallelic V(D)J rearrangement of Ig genes, transcription is known to occur on both the functional and nonfunctional alleles, generating considerable amounts of primary transcripts with out-of-frame V regions. In this study, we analyzed in cell lines and primary B cells the RNA surveillance of nonfunctional Igkappa transcripts arising from nonproductive rearrangement. We demonstrated that splicing inhibition, nonsense mediated decay and nonsense-altered splicing each have an individual partial effect that together associate into an efficient surveillance machinery, downregulating nonfunctional Igkappa mRNA. Moreover, we provide evidence that the RNA surveillance efficiency increases throughout B cell development. Whereas splicing inhibition remains constant in most cell lines, differences in nonsense mediated decay and nonsense-altered splicing are responsible for the higher RNA surveillance observed in plasma cells. Altogether, these data show that nonfunctionally rearranged alleles are subjected to active transcription but that multiple RNA surveillance mechanisms eradicate up to 90% of out-of-frame Igkappa mRNA. PMID- 20357260 TI - TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. AB - The hallmark of chronic lymphocytic leukemia (CLL) is the relentless accumulation of mature lymphocytes, mostly due to their decreased apoptosis. CD74 was recently shown to serve as a survival receptor on CLL cells. In this study, we show that stimulation of CD74 with its natural ligand, migration inhibitory factor, initiates a signaling cascade that results in upregulation of TAp63, which directly regulates CLL survival. In addition, TAp63 expression elevates the expression of the integrin VLA-4, particularly during the advanced stage of the disease. Blocking of CD74, TAp63, or VLA-4 inhibits the in vivo homing of CLL cells to the bone marrow (BM). Thus, CD74 and its target genes TAp63 and VLA-4 facilitate migration of CLL cells back to the BM, where they interact with the supportive BM environment that rescues them from apoptosis. These results could form the basis of novel therapeutic strategies aimed at blocking homing of CLL cells in their return to the BM and attenuating their survival. PMID- 20357263 TI - TLR4 is a negative regulator in noninfectious lung inflammation. AB - Low m.w. hyaluronan (LMW HA) has been shown to elicit the expression of proinflammatory cytokines and chemokines in various cells in vitro. However, the effects of this molecule in vivo are unknown. In this study, we report that intratracheal administration of LMW HA (200 kDa) causes inflammation in mouse lung. A lack of TLR4 is associated with even stronger inflammatory response in the lung as shown by increased neutrophil counts and elevated cytokine and chemokine concentrations. We also demonstrate that TLR4 anti-inflammatory signaling is dependent upon a MyD88-independent pathway. TLR4-mediated IL-1R antagonist production plays a negative regulatory role in LMW HA (200 kDa) induced lung inflammation. These data provide a molecular level explanation for the function of TLR4 in LMW HA (200 kDa)-induced lung inflammation, as inhibition of the beta form of pro-IL-1 promotes an anti-inflammatory response. PMID- 20357264 TI - An imbalance of two functionally and phenotypically different subsets of plasmacytoid dendritic cells characterizes the dysfunctional immune regulation in multiple sclerosis. AB - Plasmacytoid dendritic cells (pDCs) are instrumental in peripheral T cell tolerance and innate immunity. How pDCs control peripheral immunetolerance and local parenchymal immune response and contribute to the altered immunoregulation in autoimmune disorders in humans is poorly understood. Based on their surface markers, cytokine production, and ability to prime naive allogenic T cells, we found that purified BDCA-2(+)BDCA-4(+) pDCs consist of at least two separate populations, which differed in their response to oligodeoxynucleotides and IFNs (IFN-beta), and differently induced IL-17- or IL-10-producing T cells. To evaluate the potential immunoregulatory role of these two types of pDCs in multiple sclerosis (MS) and other human autoimmune disorders (myasthenia gravis), we studied the phenotype and regulatory function of pDCs isolated from clinically stable, untreated patients with MS (n = 16). Patients with MS showed a reversed ratio of pDC1/pDC2 in peripheral blood (4.4:1 in healthy controls, 0.69:1 in MS), a phenomenon not observed in the other autoimmune disorders. As a consequence, MS pDCs had an overall propensity to prime IL-17-secreting cells over IL-10 secreting CD4+ T cells. Immunomodulatory therapy with IFN-beta induced an increase of the pDC1 population in vivo (n = 5). Our data offer a plausible explanation for the disturbed immune tolerance in MS patients and provide evidence that immunomodulatory therapy acts at the level of reconstituting homeostasis of pDC, thus reconstituting the disturbed balance. PMID- 20357262 TI - Production of vascular endothelial growth factors from human lung macrophages induced by group IIA and group X secreted phospholipases A2. AB - Angiogenesis and lymphangiogenesis mediated by vascular endothelial growth factors (VEGFs) are main features of chronic inflammation and tumors. Secreted phospholipases A(2) (sPLA(2)s) are overexpressed in inflammatory lung diseases and cancer and they activate inflammatory cells by enzymatic and receptor mediated mechanisms. We investigated the effect of sPLA(2)s on the production of VEGFs from human macrophages purified from the lung tissue of patients undergoing thoracic surgery. Primary macrophages express VEGF-A, VEGF-B, VEGF-C, and VEGF-D at both mRNA and protein level. Two human sPLA(2)s (group IIA and group X) induced the expression and release of VEGF-A and VEGF-C from macrophages. Enzymatically-inactive sPLA(2)s were as effective as the active enzymes in inducing VEGF production. Me-Indoxam and RO092906A, two compounds that block receptor-mediated effects of sPLA(2)s, inhibited group X-induced release of VEGF A. Inhibition of the MAPK p38 by SB203580 also reduced sPLA(2)-induced release of VEGF-A. Supernatants of group X-activated macrophages induced an angiogenic response in chorioallantoic membranes that was inhibited by Me-Indoxam. Stimulation of macrophages with group X sPLA(2) in the presence of adenosine analogs induced a synergistic increase of VEGF-A release and inhibited TNF-alpha production through a cooperation between A(2A) and A(3) receptors. These results demonstrate that sPLA(2)s induce production of VEGF-A and VEGF-C in human macrophages by a receptor-mediated mechanism independent from sPLA(2) catalytic activity. Thus, sPLA(2)s may play an important role in inflammatory and/or neoplastic angiogenesis and lymphangiogenesis. PMID- 20357265 TI - CD4+CD25+Foxp3+ regulatory T cells optimize diversity of the conventional T cell repertoire during reconstitution from lymphopenia. AB - The functional capacity of the adaptive immune system is dependent on the size and the diversity of the T cell population. In states of lymphopenia, T cells are driven to proliferate to restore the T cell population size. However, different T cell clones proliferate at different rates, and some T cells experience burst like expansion called spontaneous lymphopenia-induced proliferation (LIP). These T cells are likely receiving stimulation from cognate Ags and are most responsible for inflammatory pathology that can emerge in lymphopenic states. Foxp3(+) regulatory T cells (Tregs) selectively inhibit spontaneous LIP, which may contribute to their ability to prevent lymphopenia-associated autoimmunity. We hypothesized that another potential negative consequence of unrestrained spontaneous LIP is constriction of the total T cell repertoire. We demonstrate that the absence of Foxp3(+) Tregs during the period of immune reconstitution results in the development of TCR repertoire "holes" and the loss of Ag-specific responsiveness to infectious microorganisms. In contrast, the presence of Tregs during the period of immune reconstitution preserves optimal TCR diversity and foreign Ag responsiveness. This finding contrasts with the generally accepted immunosuppressive role of Tregs and provides another example of Treg activity that actually enhances immune function. PMID- 20357266 TI - Human endometrial stromal cell rho GTPases have opposing roles in regulating focal adhesion turnover and embryo invasion in vitro. AB - Implantation of the embryo into the uterine compartment is a multistep event involving attachment of the embryo to the endometrial epithelia, followed by invasion of the embryo through the endometrial stroma. RHOA, RAC1, and CDC42 are members of the Rho GTPase family of proteins, which control cell functions such as cell migration and cytoskeletal reorganization. Herein, using a heterologous in vitro coculture model, we show that implantation of mouse blastocysts into human endometrial stromal cells (hESCs) is regulated by Rho GTPase activity in hESCs. Whereas iRNA-mediated silencing of RAC1 expression in hESCs led to inhibition of embryo implantation, silencing of either RHOA or CDC42 in hESCs promoted embryo implantation in coculture assays. Analysis of downstream signaling pathways demonstrated that RAC1 silencing was associated with decreased focal adhesion disassembly and resulted in large focal adhesion complexes in hESCs. In contrast, RHOA or CDC42 silencing resulted in perturbed focal adhesion assembly, leading to a decrease in the number of focal adhesions observed. Furthermore, inhibition of Rho signaling using a Rho kinase inhibitor, Y27632, led to decreased activation of protein tyrosine kinase 2 (PTK2, also called focal adhesion kinase) and decreased focal adhesion assembly. Importantly, perturbation of focal adhesion turnover in hESCs, mediated by PTK2 silencing, resulted in inhibition of embryo implantation into hESC monolayers. These findings suggest that Rho GTPase-PTK2-dependent remodeling of the endometrial stromal cell compartment may be critical for successful embryo implantation. PMID- 20357268 TI - Species-specific differences in the activity and nuclear localization of murine and bovine phospholipase C zeta 1. AB - Injection of mammalian sperm extracts or cRNA of the sperm-specific phospholipase C zeta 1 (PLCZ1) has been shown to trigger repetitive oscillations in the concentration of free calcium ([Ca(2+)](i)), leading to oocyte activation and embryo development in all mammals studied to date. While PLCZ1 has cross-species activity, it has also been observed that species-specific differences may exist in the frequency and pattern of the resulting [Ca(2+)](i) oscillations following PLCZ1 cRNA injection into oocytes of different species. Accordingly, we used a crossover design strategy to directly investigate the activity of murine and bovine PLCZ1 in both murine and bovine oocytes. In murine oocytes, injection of murine Plcz1 cRNA induced [Ca(2+)](i) oscillations at 10-fold lower concentrations than bovine PLCZ1, although in bovine oocytes bovine PLCZ1 was more effective than murine Plcz1 at inducing [Ca(2+)](i) oscillations. Investigation of ITPR1 (IP(3)R1) down-regulation in bovine oocytes by PLCZ1 cRNA also showed that bovine PLCZ1 was more active in homologous oocytes. To determine whether these PLCZs exhibited similar cellular distribution, Venus-tagged PLCZ1 cRNA was injected into oocytes, and PLCZ1 was overexpressed. Bovine PLCZ1 failed to accumulate in the pronucleus (PN) of bovine or murine zygotes, despite possessing a putative nuclear localization signal. Conversely, murine PLCZ1 accumulated in the PN of both murine and bovine zygotes. These results demonstrate that murine PLCZ1 and bovine PLCZ1 possess species-specific differences in activity and suggest potential differences in the mode of action of the protein between the two species. Variation in sperm PLCZ1 protein content among species, along with oocyte-specific differences in the localization and availability of PLCZ1 substrates, may further contribute to optimize the activation stimulus to enhance embryo development. PMID- 20357267 TI - Acute and chronic effects of oral genistein administration in neonatal mice. AB - Soy-based infant formulas are widely used in the United States and some other countries. These formulas contain high levels of the estrogenic isoflavone genistein, leading to concern that neonatal genistein exposure could cause acute and/or long-term adverse effects on reproductive and other organs. However, previous work to assess genistein effects in rodent models has not typically replicated the route of delivery and/or serum genistein concentrations reported for soy formula-fed human infants. Our objective was to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants. Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and non-reproductive organs were assessed after dosing and during subsequent development. Neonatal treatment resulted in changes both at the completion of dosing (PND 5) and in adult animals. At PND 5, neonatal genistein treatment caused increased relative uterine weight and down regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (MOFs) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age despite normal fertility in these mice. The immediate and long-term effects in this neonatal animal model raise concerns that high serum concentrations of genistein are estrogenic and could potentially impact the development of human infants fed soy formula. PMID- 20357269 TI - First evidence of bone morphogenetic protein 1 expression and activity in sheep ovarian follicles. AB - Bone morphogenetic protein (BMP) 1 is a vertebrate metalloproteinase of the astacin family. BMP1 plays a key role in regulating the formation of the extracellular matrix (ECM), particularly by processing the C-propeptide of fibrillar procollagens. BMP1 also promotes BMP signaling by releasing BMP signaling molecules from complexes with the BMP-antagonist chordin. As a result of BMP1's dual role in both ECM formation and BMP signaling, we hypothesized that BMP1 could play a role in ovarian physiology. Using the sheep ovary as a model system, we showed that BMP1 was expressed in the ovary throughout early fetal stages to adulthood. Furthermore, in adult ovaries, BMP1 was expressed along with chordin, BMP4, and twisted gastrulation, which together form an extracellular regulatory complex for BMP signaling. Within ovine ovaries, immunohistochemical localization demonstrated that BMP1 was present in granulosa cells at all stages of follicular development, from primordial to large antral follicles, and that the levels of BMP1 were not affected by the final follicle selection mechanism. In cultured granulosa cells, BMP1 expression was not affected by gonadotropins, but BMP4 and activin A had opposing effects on the levels of BMP1 mRNA. BMP1 appeared to be secreted into the follicular fluid of antral follicles, where it is able to exert procollagen C-proteinase and chordinase activities. Interestingly, BMP1 activity in follicular fluid decreased with follicular growth. PMID- 20357270 TI - MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells. AB - MicroRNAs (miRNAs) play important roles in many developmental processes, including cell differentiation and apoptosis. Transition of proliferative ovarian granulosa cells to terminally differentiated luteal cells in response to the ovulatory surge of luteinizing hormone (LH) involves rapid and pronounced changes in cellular morphology and function. MicroRNA 21 (miR-21, official symbol Mir21) is one of three highly LH-induced miRNAs in murine granulosa cells, and here we examine the function and temporal expression of Mir21 within granulosa cells as they transition to luteal cells. Granulosa cells were transfected with blocking (2'-O-methyl) and locked nucleic acid (LNA-21) oligonucleotides, and mature Mir21 expression decreased to one ninth and one twenty-seventh of its basal expression, respectively. LNA-21 depletion of Mir21 activity in cultured granulosa cells induced apoptosis. In vivo, follicular granulosa cells exhibit a decrease in cleaved caspase 3, a hallmark of apoptosis, 6 h after the LH/human chorionic gonadotropin surge, coincident with the highest expression of mature Mir21. To examine whether Mir21 is involved in regulation of apoptosis in vivo, mice were treated with a phospho thioate-modified LNA-21 oligonucleotide, and granulosa cell apoptosis was examined. Apoptosis increased in LNA-21-treated ovaries, and ovulation rate decreased in LNA-21-treated ovaries, compared with their contralateral controls. We have examined a number of Mir21 apoptotic target transcripts identified in other systems; currently, none of these appear to play a role in the induction of ovarian granulosa cell apoptosis. This study is the first to implicate the antiapoptotic Mir21 (an oncogenic miRNA) as playing a clear physiologic role in normal tissue function. PMID- 20357271 TI - Differential expression of the enzymatic system controlling synthesis, metabolism, and transport of PGF2 alpha in human fetal membranes. AB - The present study investigated the expression of genes and proteins associated with PGF2alpha biosynthesis, catabolism, and transport in matched amnion and choriodecidua of human term placenta. The concentration of PGF2alpha within fetal membranes depends on the balance between complex enzymatic systems responsible for, respectively, its synthesis-by prostaglandin-endoperoxide synthase 2 (PTGS2) and members of the aldo-keto reductase (AKR) family, AKR1C3 and AKR1B1-and its catabolic inactivation-through hydroxy-prostaglandin-dehydrogenase (HPGD). We observed that AKR1C3 shows equal basal expression (mRNA and protein) in choriodecidua and amnion but that AKR1B1 exhibits preferential expression in the choriodecidua. Expression of HPGD and solute carrier organic anion transporter family member 2A1 (SLCO2A1) was found primarily in the choriodecidua. We also evaluated whether an inflammatory environment induced by the gram-negative bacterial endotoxin lipopolysaccharide (LPS) affects expression of each candidate enzymes. The amnion responded to LPS with a small but significant decrease of AKR1B1 mRNA expression. In contrast, we found a significant increase in PTGS2 and AKR1C3 mRNA expression in choriodecidua after LPS challenge, but such regulation was confirmed only at protein levels for PTGS2 and not for AKR1C3. Our results suggest that the choriodecidua appears to be the main tissue, which expresses maximally all the components (synthesis, degradation, and transport) controlling PGF2alpha levels. PMID- 20357272 TI - Role of apoptosis and cell proliferation in the testicular dynamics of seasonal breeding mammals: a study in the Iberian mole, Talpa occidentalis. AB - Apoptosis and cell proliferation are two important cellular processes known to be involved in the normal functioning of the testis in nonseasonally breeding mammals, but there is some controversy concerning their roles in the gonads of males from seasonally breeding species. We have studied the processes of apoptosis and cell proliferation in the testes of males of the Iberian mole (Talpa occidentalis), a species showing a strict seasonal reproduction pattern. Both males and females are sexually active during the winter and completely inactive in the summer, with two transitional periods, in the autumn and the spring. Adult males from these four reproductive stages were captured, and their testes were immunohistochemically studied for the presence of apoptotic and proliferation molecular markers as well for other testicular and meiotic cell specific markers. We found that apoptosis varies in a season-dependent manner in the testes of male moles, affecting mainly late zygotene and pachytene cells during the period of sexual inactivity, but it does not differentially affect the number of Sertoli cells. More interestingly, apoptosis is not responsible for the massive germ-cell depletion occurring during mole testis regression. In addition, a wave of spermatogonial cell proliferation appears to restore the number of spermatogonia lost during the period of testis inactivity. According to current knowledge, data from moles indicate that mammals do not form a homogeneous group regarding the mechanisms by which the cell-content dynamics are regulated in the testes of males from seasonally breeding species. PMID- 20357273 TI - Germline replacement by transfer of primordial germ cells into partially sterilized embryos in the chicken. AB - We report a novel technique for almost complete replacement of the recipient germline with donor germ cells in the chicken. Busulfan solubilized in a sustained-release emulsion was injected into the yolk of fertile eggs before incubation. A dose of 100 microg was found to provide the best outcome in terms of reducing the number of endogenous primordial germ cells (PGCs) in embryonic gonads (0.6% of control numbers) and hatchability (36.4%). This was applied for preparing partially sterilized embryos to serve as recipients for the transfer of exogenous PGCs. Immunohistochemical analysis showed that the proportion of donor PGCs in busulfan-treated embryos was significantly higher than in controls (98.6% vs. 6.4%). Genetic cross-test analysis revealed that the germline transmission rate in busulfan-treated chickens was significantly higher than in controls (99.5% vs. 6.0%). Of 11 chimeras, 7 produced only donor-derived progenies, suggesting that these produced only donor-derived gametes in the recipient's gonads. This novel germline replacement technique provides a powerful tool for studying germline differentiation, for generating transgenic individuals, and for conserving genetic resources in birds. PMID- 20357274 TI - Implementation and the legacy of health care reform. PMID- 20357275 TI - Cost consciousness in patient care--what is medical education's responsibility? PMID- 20357276 TI - Malpractice reform--opportunities for leadership by health care institutions and liability insurers. PMID- 20357278 TI - Images in clinical medicine. Cycling for freezing of gait. PMID- 20357277 TI - Pain management in the cirrhotic patient: the clinical challenge. AB - Pain management in patients with cirrhosis is a difficult clinical challenge for health care professionals, and few prospective studies have offered an evidence based approach. In patients with end-stage liver disease, adverse events from analgesics are frequent, potentially fatal, and often avoidable. Severe complications from analgesia in these patients include hepatic encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding, which can result in substantial morbidity and even death. In general, acetaminophen at reduced dosing is a safe option. In patients with cirrhosis, nonsteroidal anti-inflammatory drugs should be avoided to avert renal failure, and opiates should be avoided or used sparingly, with low and infrequent dosing, to prevent encephalopathy. For this review, we searched the available literature using PubMed and MEDLINE with no limits. PMID- 20357279 TI - Improving the security and privacy of implantable medical devices. PMID- 20357280 TI - Trajectories of disability in the last year of life. AB - BACKGROUND: Despite the importance of functional status to older persons and their families, little is known about the course of disability at the end of life. METHODS: We evaluated data on 383 decedents from a longitudinal study involving 754 community-dwelling older persons. None of the subjects had disability in essential activities of daily living at the beginning of the study, and the level of disability was ascertained during monthly interviews for more than 10 years. Information on the conditions leading to death was obtained from death certificates and comprehensive assessments that were completed at 18-month intervals after the baseline assessment. RESULTS: In the last year of life, five distinct trajectories were identified, from no disability to the most severe disability: 65 subjects had no disability (17.0%), 76 had catastrophic disability (19.8%), 67 had accelerated disability (17.5%), 91 had progressive disability (23.8%), and 84 had persistently severe disability (21.9%). The most common condition leading to death was frailty (in 107 subjects [27.9%]), followed by organ failure (in 82 subjects [21.4%]), cancer (in 74 subjects [19.3%]), other causes (in 57 subjects [14.9%]), advanced dementia (in 53 subjects [13.8%]), and sudden death (in 10 subjects [2.6%]). When the distribution of the disability trajectories was evaluated according to the conditions leading to death, a predominant trajectory was observed only for subjects who died from advanced dementia (67.9% of these subjects had a trajectory of persistently severe disability) and sudden death (50.0% of these subjects had no disability). For the four other conditions leading to death, no more than 34% of the subjects had any of the disability trajectories. The distribution of disability trajectories was particularly heterogeneous among the subjects with organ failure (from 12.2 to 32.9% of the subjects followed a specific trajectory) and frailty (from 14.0 to 27.1% of the subjects followed a specific trajectory). CONCLUSIONS: In most of the decedents, the course of disability in the last year of life did not follow a predictable pattern based on the condition leading to death. PMID- 20357282 TI - Glycogenin-1 deficiency and inactivated priming of glycogen synthesis. AB - Glycogen, which serves as a major energy reserve in cells, is a large, branched polymer of glucose molecules. We describe a patient who had muscle weakness, associated with the depletion of glycogen in skeletal muscle, and cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart. The skeletal muscle showed a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation. Western blotting showed the presence of unglucosylated glycogenin-1 in the muscle and heart. Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other. The missense mutation resulted in inactivation of the autoglucosylation of glycogenin-1 that is necessary for the priming of glycogen synthesis in muscle. PMID- 20357284 TI - Clinical practice. Prolactinomas. PMID- 20357283 TI - Advance directives and outcomes of surrogate decision making before death. AB - BACKGROUND: Recent discussions about health care reform have raised questions regarding the value of advance directives. METHODS: We used data from survey proxies in the Health and Retirement Study involving adults 60 years of age or older who had died between 2000 and 2006 to determine the prevalence of the need for decision making and lost decision-making capacity and to test the association between preferences documented in advance directives and outcomes of surrogate decision making. RESULTS: Of 3746 subjects, 42.5% required decision making, of whom 70.3% lacked decision-making capacity and 67.6% of those subjects, in turn, had advance directives. Subjects who had living wills were more likely to want limited care (92.7%) or comfort care (96.2%) than all care possible (1.9%); 83.2% of subjects who requested limited care and 97.1% of subjects who requested comfort care received care consistent with their preferences. Among the 10 subjects who requested all care possible, only 5 received it; however, subjects who requested all care possible were far more likely to receive aggressive care as compared with those who did not request it (adjusted odds ratio, 22.62; 95% confidence interval [CI], 4.45 to 115.00). Subjects with living wills were less likely to receive all care possible (adjusted odds ratio, 0.33; 95% CI, 0.19 to 0.56) than were subjects without living wills. Subjects who had assigned a durable power of attorney for health care were less likely to die in a hospital (adjusted odds ratio, 0.72; 95% CI, 0.55 to 0.93) or receive all care possible (adjusted odds ratio, 0.54; 95% CI, 0.34 to 0.86) than were subjects who had not assigned a durable power of attorney for health care. CONCLUSIONS: Between 2000 and 2006, many elderly Americans needed decision making near the end of life at a time when most lacked the capacity to make decisions. Patients who had prepared advance directives received care that was strongly associated with their preferences. These findings support the continued use of advance directives. PMID- 20357285 TI - Images in clinical medicine. Varicella pneumonia in an adult. PMID- 20357286 TI - Clinical problem-solving. More than meets the ear. PMID- 20357287 TI - Chemoprevention of prostate cancer. PMID- 20357288 TI - Reversing the code status of advance directives? PMID- 20357289 TI - MMP12, lung function, and COPD in high-risk populations. PMID- 20357291 TI - Discharge planning and rates of readmissions. PMID- 20357290 TI - Sensitive cardiac troponin T assay. PMID- 20357292 TI - Molecular basis of colorectal cancer. PMID- 20357293 TI - More on integrated delivery systems. PMID- 20357294 TI - Human parvovirus B19-associated myocarditis. PMID- 20357295 TI - Exposure-response analyses of the effects of pregabalin in patients with fibromyalgia using daily pain scores and patient global impression of change. AB - Data from 4 phase 2/3 studies were pooled to characterize the exposure response of daily pregabalin (150-600 mg) in patients with fibromyalgia using self assessed daily pain scores (PAIN) and end-of-treatment patient global impression of change (PGIC). The exposure responses of both endpoints were characterized by an Emax model using nonlinear mixed-effects modeling (NONMEM). Drug effect on PAIN relative to placebo was significant with additional maximum effect of 1.51 points on the logit scale and EC50 of 1.54 ng/mL (dose of 174 mg) and a rapid onset (half-life of 11 hours), consistent with the half-life of the drug. The decrease in PAIN with placebo occurred more slowly, reaching maximum response (1.52 points on the logit scale) after 1 month. Drug response in fibromyalgia was dependent on age and sex, with greater PAIN reduction in older patients, in addition to the effect of creatinine clearance, and in females. For PGIC, administration of pregabalin resulted in an increase in the proportion of patients reporting improvement with an ED50 of 228 mg. The analyses support the recommended dose of pregabalin in patients with fibromyalgia of 300 to 450 mg/d. PMID- 20357296 TI - Pacemaker malfunction induced by a pharmaco-metabolic "perfect storm": a brief report. PMID- 20357297 TI - Should our major classifications of mental disorders be revised? AB - Our major classification systems (DSM and ICD) face three main problems: the high rates of 'comorbidity' that are produced by our present diagnostic rules, the increasing use of 'not elsewhere classified' (NEC) by practising clinicians, and the fact that each new edition is longer and more complex than the one preceding it. A major simplification of the chapter structure used by each classification might pave the way to address these problems. PMID- 20357298 TI - Utility of computerised cognitive-behavioural therapy for depression. AB - A recent study found that people with depression identified in the community recovered equally well given unsupported computerised cognitive-behavioural therapy (CBT), general practitioner treatment or a combination of the two, even if they did not comply. The results are different from those reported elsewhere. Could natural remission explain the finding? PMID- 20357299 TI - Cognitive model of caregiving in psychosis. AB - BACKGROUND: There is a long history of research into the attributes of carers of people with psychosis, but few interventions target their distress or their difficulties. AIMS: To describe an empirically based model of the relationships of those caring for people with psychosis to inform clinical and theoretical advances. METHOD: We developed a model of informal carer relationships in psychosis, based on an integration of the literature elaborating the concept of expressed emotion. The model accounts for divergent outcomes of three relationship types: positive, overinvolved and critical/hostile relationships. RESULTS: Good evidence supports a number of hypotheses concerning the origin and maintenance of these relationship outcomes, which relate to specific differences in carer attributions, illness perceptions, coping behaviour, social support, distress, depression and low self-esteem predicted by our model. We propose that interventions aimed at modifying the specific maintenance factors involved in the different styles of relationships will optimise therapeutic change both for service users with psychosis and for their carers. CONCLUSIONS: Family work in psychosis, which improves relationships through problem-solving, reduces service user relapse. It is now time to consider theory-based interventions focused on improving carer outcomes. PMID- 20357300 TI - Ethnic minorities and mental health services: developing a more sustainable approach. PMID- 20357301 TI - Efficacy and acceptability of mood stabilisers in the treatment of acute bipolar depression: systematic review. AB - BACKGROUND: Although people with bipolar disorder spend more time in a depressed than manic state, little evidence is available to guide the treatment of acute bipolar depression. AIMS: To compare the efficacy, acceptability and safety of mood stabiliser monotherapy with combination and antidepressant treatment in adults with acute bipolar depression. METHOD: Systematic review and meta-analysis of randomised, double-blind controlled trials. RESULTS: Eighteen studies with a total 4105 participants were analysed. Mood stabiliser monotherapy was associated with increased rates of response (relative risk (RR) = 1.30, 95% CI 1.16-1.44, number needed to treat (NNT) = 10, 95% CI 7-18) and remission (RR = 1.51, 95% CI 1.27-1.79, NNT = 8, 95% CI 5-14) relative to placebo. Combination therapy was not statistically superior to monotherapy. Weight gain, switching and suicide rates did not differ between groups. No differences were found between individual medications or drug classes for any outcome. CONCLUSIONS: Mood stabilisers are moderately efficacious for acute bipolar depression. Extant studies are few and limited by high rates of discontinuation and short duration. Further study of existing and novel agents is required. PMID- 20357304 TI - Social communication deficits in disruptive primary-school children. AB - BACKGROUND: Parent and teacher data, from questionnaire surveys, suggest that school-identified disruptive children often have pragmatic language deficits of an autistic type. AIMS: This replication study aimed to confirm earlier findings, using individual clinical assessment to investigate traits of autism-spectrum disorder in disruptive children. METHOD: Persistently disruptive children (n = 26) and a comparison group (n = 22) were recruited from primary schools in a deprived inner-city area. Measures included standardised autism diagnostic interviews (with parents) and tests of IQ, social cognition, theory of mind and attention (with children). RESULTS: The disruptive children possessed poorer pragmatic language skills (P<0.0001) and mentalising abilities (P<0.05) than comparisons. Nine disruptive children (35%) met ICD-10 criteria for atypical autism or Asperger syndrome. CONCLUSIONS: Many persistently disruptive children have undetected disorders of social communication, which are of potential aetiological significance. PMID- 20357302 TI - Autism, ethnicity and maternal immigration. AB - BACKGROUND: A growing number of European studies, particularly from Nordic countries, suggest an increased frequency of autism in children of immigrant parents. In contrast, North American studies tend to conclude that neither maternal ethnicity nor immigrant status are related to the rate of autism spectrum disorders. AIMS: To examine the hypotheses that maternal ethnicity and/or immigration are linked to the rate of childhood autism-spectrum disorders. METHOD: Retrospective case-note analysis of all 428 children diagnosed with autism-spectrum disorders presenting to the child development services in two centres during a 6-year period. RESULTS: Mothers born outside Europe had a significantly higher risk of having a child with an autism-spectrum disorder compared with those born in the UK, with the highest risk observed for the Caribbean group (relative risks (RRs) in the two centres: RR = 10.01, 95% CI 5.53 18.1 and RR = 8.89, 95% CI 5.08-15.5). Mothers of Black ethnicity had a significantly higher risk compared with White mothers (RR = 8.28, 95% CI 5.41 12.7 and RR = 3.84, 95% CI 2.93-5.02). Analysis of ethnicity and immigration factors together suggests the increased risk is predominately related to immigration. CONCLUSIONS: Maternal immigration is associated with substantial increased risk of autism-spectrum disorders with differential risk according to different region of birth and possibly ethnicity. PMID- 20357305 TI - Outcomes of occasional cannabis use in adolescence: 10-year follow-up study in Victoria, Australia. AB - BACKGROUND: Regular adolescent cannabis use predicts a range of later drug use and psychosocial problems. Little is known about whether occasional cannabis use carries similar risks. AIMS: To examine associations between occasional cannabis use during adolescence and psychosocial and drug use outcomes in young adulthood; and modification of these associations according to the trajectory of cannabis use between adolescence and age 20 years, and other potential risk factors. METHOD: A 10-year eight-wave cohort study of a representative sample of 1943 secondary school students followed from 14.9 years to 24 years. RESULTS: Occasional adolescent cannabis users who continued occasional use into early adulthood had higher risks of later alcohol and tobacco dependence and illicit drug use, as well as being less likely to complete a post-secondary qualification than non-users. Those using cannabis at least weekly either during adolescence or at age 20 were at highest risk of drug use problems in young adulthood. Adjustment for smoking in adolescence reduced the association with later educational achievement, but associations with drug use problems remained. CONCLUSIONS: Occasional adolescent cannabis use predicts later drug use and educational problems. Partial mediation by tobacco use raises a possibility that differential peer affiliation may play a role. PMID- 20357306 TI - Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk. AB - BACKGROUND: The nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear. AIMS: To re examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year. METHOD: Symptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n = 101) were re-analysed in the context of duration of untreated illness (DUI). RESULTS: At admission, those with long DUI were more likely to have lower scores on tension derived from the Present State Examination, exhibited more behaviour threatening to others and more bizarre behaviour, were more likely to be single, to live alone or dependently, to be unemployed and to have experienced more adverse life events prior to admission. Logistic regression showed that diminished tension, bizarre behaviour and unemployed status independently increased the risk of relapse, bizarre behaviour making the single biggest contribution. Tension did not remain significant with log-transformation of data. CONCLUSIONS: Findings are consistent with the conclusion that long DUI can reflect characteristics of the psychosis itself rather than delay in treatment. PMID- 20357307 TI - Burden of chronic physical conditions and mental disorders in primary care. AB - BACKGROUND: The World Health Organization (WHO) has stated that the three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depression and ischaemic heart disease. AIMS: To estimate health-related quality of life (HRQoL) and quality-adjusted life-year (QALY) losses associated with mental disorders and chronic physical conditions in primary healthcare using data from the diagnosis and treatment of mental disorders in primary care (DASMAP) study, an epidemiological survey carried out with primary care patients in Catalonia (Spain). METHOD: A cross-sectional survey of a representative sample of 3815 primary care patients. A preference-based measure of health was derived from the 12-item Short Form Health Survey (SF-12): the Short Form-6D (SF-6D) multi attribute health-status classification. Each profile generated by this questionnaire has a utility (or weight) assigned. We used non-parametric quantile regressions to model the association between both mental disorders and chronic physical condition and SF-6D scores. RESULTS: Conditions associated with SF-6D were: mood disorders, beta = -0.20 (95% CI -0.18 to -0.21); pain, beta = -0.08 (95%CI -0.06 to -0.09) and anxiety, beta = -0.04 (95% CI -0.03 to -0.06). The top three causes of QALY losses annually per 100 000 participants were pain (5064), mood disorders (2634) and anxiety (805). CONCLUSIONS: Estimation of QALY losses showed that mood disorders ranked second behind pain-related chronic medical conditions. PMID- 20357308 TI - Psalm 38: A man with major depression - psychiatry in the Old Testament. PMID- 20357281 TI - Effect of dutasteride on the risk of prostate cancer. AB - BACKGROUND: We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease. METHODS: In this 4-year, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in the study if they were 50 to 75 years of age, had a prostate-specific antigen (PSA) level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years. RESULTS: Among 6729 men who underwent a biopsy or prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group, representing a relative risk reduction with dutasteride of 22.8% (95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001). Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group (P=0.81). During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group, as compared with only 1 in the placebo group (P=0.003). Dutasteride therapy, as compared with placebo, resulted in a reduction in the rate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia, except that in our study, as compared with previous studies, the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group (0.7% [30 men] vs. 0.4% [16 men], P=0.03). CONCLUSIONS: Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate cancer detected on biopsy and improved the outcomes related to benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00056407.) PMID- 20357309 TI - Economic evaluation of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial. AB - BACKGROUND: Evidence about the cost-effectiveness and cost utility of computerised cognitive-behavioural therapy (CCBT) is still limited. Recently, we compared the clinical effectiveness of unsupported, online CCBT with treatment as usual (TAU) and a combination of CCBT and TAU (CCBT plus TAU) for depression. The study is registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236). AIMS: To assess the cost-effectiveness of CCBT compared with TAU and CCBT plus TAU. METHOD: Costs, depression severity and quality of life were measured for 12 months. Cost-effectiveness and cost-utility analyses were performed from a societal perspective. Uncertainty was dealt with by bootstrap replications and sensitivity analyses. RESULTS: Costs were lowest for the CCBT group. There are no significant group differences in effectiveness or quality of life. Cost-utility and cost-effectiveness analyses tend to be in favour of CCBT. CONCLUSIONS: On balance, CCBT constitutes the most efficient treatment strategy, although all treatments showed low adherence rates and modest improvements in depression and quality of life. PMID- 20357310 TI - Cost-effectiveness of a stepped care intervention to prevent depression and anxiety in late life: randomised trial. AB - BACKGROUND: There is an urgent need for the development of cost-effective preventive strategies to reduce the onset of mental disorders. AIMS: To establish the cost-effectiveness of a stepped care preventive intervention for depression and anxiety disorders in older people at high risk of these conditions, compared with routine primary care. METHOD: An economic evaluation was conducted alongside a pragmatic randomised controlled trial (ISRCTN26474556). Consenting individuals presenting with subthreshold levels of depressive or anxiety symptoms were randomly assigned to a preventive stepped care programme (n = 86) or to routine primary care (n = 84). RESULTS: The intervention was successful in halving the incidence rate of depression and anxiety at euro563 ( pound412) per recipient and euro4367 ( pound3196) per disorder-free year gained, compared with routine primary care. The latter would represent good value for money if the willingness to pay for a disorder-free year is at least euro5000. CONCLUSIONS: The prevention programme generated depression- and anxiety-free survival years in the older population at affordable cost. PMID- 20357311 TI - Robert Schumann's contribution to the genetics of psychosis - psychiatry in music. PMID- 20357312 TI - Early intervention in panic: pragmatic randomised controlled trial. AB - BACKGROUND: Many people suffer from subthreshold and mild panic disorder and are at risk of developing more severe panic disorder. AIMS: This study (trial registration: ISRCTN33407455) was conducted to evaluate the effectiveness of an early group intervention based on cognitive-behavioural principles to reduce panic disorder symptomatology. METHOD: Participants with subthreshold or mild panic disorder were recruited from the general population and randomised to the intervention (n = 109) or a waiting-list control group (n = 108). The course was offered by 17 community mental health centres. RESULTS: In the early intervention group, 43/109 (39%) participants presented with a clinically significant change on the Panic Disorder Severity Scale-Self Report (PDSS-SR) v. 17/108 (16%) in the control group (odds ratio (OR) for favourable treatment response 3.49, 95% CI 1.77-6.88, P = 0.001). The course also had a positive effect on DSM-IV panic disorder status (OR = 1.96, 95% CI=1.05-3.66, P = 0.037). The PDSS-SR symptom reduction was also substantial (between-group standardised mean difference of 0.68). The effects were maintained at 6-month follow-up. CONCLUSIONS: People presenting with subthreshold and mild panic disorder benefit from this brief intervention. PMID- 20357313 TI - Sample bias may obscure results. PMID- 20357314 TI - Antipsychotics and borderline personality disorder. PMID- 20357316 TI - Microdialysis as a method for biochemical and physiological studies of the porcine and human disc. AB - At present, no minimally invasive technique exists for the continuous evaluation of the biochemistry of animal and human intervertebral discs, but for research purposes microdialysis may be such a new technique. Thus, the aims of this study were to (1) evaluate if microdialysis can be used successfully in lumbar porcine disc and (2) develop a suitable procedure for the application of microdialysis in the human disc. Conventional specific pathogen-free pigs were used to evaluate cannulation (n = 2) and then insertion of a 10 mm microdialysis membrane, including recovery of a dialysate from the nucleus pulposus (n = 6). The procedure was performed immediately after euthanasia and aided by fluoroscopy to guide the needle and confirm catheter placement. Access to lumbar porcine disc was obtained with an 18 G 2 in. needle applied at a 35-45 degrees angle from the sagittal plane, and took less than 8 min to perform. At a 0.5 microL/min flush rate, dialysates could be recovered and analysable amounts of glucose, lactate and pyruvate were obtained. In one human cadaver, the L4-L5 disc was accessed by a 19 G 3 in. needle inserted at a 35-40 degrees angle. It was possible to apply 10 mm as well as 30 mm microdialysis membranes in the nucleus. In both species the position of the membranes was verified by direct fluoroscopy and with contrast fluid. The results obtained from porcine and human cadavers are promising, and encourage further in vivo studies using microdialysis technique on intervertebral discs. PMID- 20357317 TI - Combination medium of cryoprotective agents containing L-glutamine and methyl {beta}-cyclodextrin in a preincubation medium yields a high fertilization rate for cryopreserved C57BL/6J mouse sperm. AB - Recently, a vast number of genetically-engineered mice have been created in various laboratories worldwide, all of which need to be effectively archived. The cryopreservation of mouse sperm provides a simple and economical means of storing the mice in mouse resource facilities. The current protocol for sperm cryopreservation using 18% raffinose pentahydrate and 3% skim milk (R18S3) has been adopted in most laboratories. In general, we can attain relatively high fertilization rates for frozen/thawed sperm in many inbred and F1 hybrid strains. However, the sperm of C57BL/6J mice shows an extremely low fertility rate after freezing and thawing (0-20%). In this study, we attempted to improve the low fertility of frozen/thawed C57BL/6J mouse sperm. Our results showed that a combination of R18S3 containing l-glutamine and methyl-beta-cyclodextrin (MBCD) in a preincubation medium dramatically increased the rate of fertilization (69.2 +/- 12.2%). Furthermore, the developmental potencies of two-cell embryos produced by frozen/thawed sperm to live young were normal (fresh: 46.0 +/- 8.2%, frozen/thawed: 51.5 +/- 11.1%). In summary, we conclude that a new method of sperm cryopreservation and in vitro fertilization using modified R18S3 with l glutamine and MBCD in a preincubation medium yields a high fertilization rate for frozen/thawed C57BL/6J strain sperm. Furthermore, the new method provides a reliable archiving and reproducing system for genetically-engineered mice using sperm cryopreservation. PMID- 20357318 TI - Use of endoscopy for management of acute upper gastrointestinal bleeding in the UK: results of a nationwide audit. AB - OBJECTIVES: To examine the use of endoscopy in the UK for acute upper gastrointestinal bleeding (AUGIB) and compare with published standards. To assess the organisation of endoscopy services for AUGIB in the UK. To examine the relationship between outcomes and out of hours (OOH) service provision. DESIGN: Multi-centre cross sectional clinical audit. SETTING: All UK hospitals accepting admissions with AUGIB. PATIENTS: All adults (>or=16 yrs) presenting with AUGIB between 1st May and 30th June 2007. DATA: Collection A custom designed web-based reporting tool was used to collect data on patient characteristics, comorbidity and haemodynamic status at presentation to calculate the Rockall score, use and timing of endoscopy, treatment including endoscopic, rebleeding and in-hospital mortality. A mailed questionnaire was used to collect data on facilities and service organisation. RESULTS: Data on 6750 patients (median age 68 years) were analysed from 208 hospitals. 74% underwent inpatient endoscopy; of these 50% took place within 24 h of presentation, 82% during normal working hours and 3% between midnight and 8 am. Of patients deemed high-risk (pre-endoscopy Rockall score >or=5) only 55% were endoscoped within 24 h and 14% waited >or=72 h for endoscopy. Lesions with a high risk of rebleeding were present in 28% of patients of whom 74% received endoscopic therapy. Further bleeding was evident in 13% and mortality in those endoscoped was 7.4% (95% CI 6.7% to 8.1%). In 52% of hospitals a consultant led out of hours (OOH) endoscopy rota existed; in these hospitals 20% of first endoscopies were performed OOH compared with 13% in those with no OOH rota and endoscopic therapy was more likely to be administered (25% vs 21% in hospitals with no OOH rota). The risk adjusted mortality ratio was higher (1.21, p=0.10, (95%CI 0.96 to 1.51)) in hospitals without such rotas. CONCLUSIONS: This audit has found continuing delays in performing endoscopy after AUGIB and underutilisation of standard endoscopic therapy particularly for variceal bleeding. In hospitals with a formal OOH endoscopy rota patients received earlier endoscopy, were more likely to receive endoscopic therapy and may have a lower mortality. PMID- 20357319 TI - The influence of the size of the component on the outcome of resurfacing arthroplasty of the hip: a review of the literature. AB - The survivorship of contemporary resurfacing arthroplasty of the hip using metal on-metal bearings is better than that of first generation designs, but short-term failures still occur. The most common reasons for failure are fracture of the femoral neck, loosening of the component, osteonecrosis of the femoral head, reaction to metal debris and malpositioning of the component. In 2008 the Australian National Joint Registry reported an inverse relationship between the size of the head component and the risk of revision in resurfacing hip arthroplasty. Hips with a femoral component size of /= 55 mm irrespective of gender. We have reviewed the literature to explore this observation and to identify possible reasons including the design of the implant, loading of the femoral neck, the orientation of the component, the production of wear debris and the effects of metal ions, penetration of cement and vascularity of the femoral head. Our conclusion is that although multifactorial, the most important contributors to failure in resurfacing arthroplasty of the hip are likely to be the design and geometry of the component and the orientation of the acetabular component. PMID- 20357320 TI - Orthopaedic training: 'run through' or uncoupled. AB - The Postgraduate Medical Education and Training Board wants either 'run through' or 'uncoupled' orthopaedic training to be adopted throughout the United Kingdom but it is not willing to let both continue together as is the current situation. This annotation explores the argument for and against 'run through' training. PMID- 20357321 TI - The Freeman femoral component with hydroxyapatite coating and retention of the neck: an update with a minimum follow-up of 17 years. AB - The outcome at ten years of 100 Freeman hip stems (Finsbury Orthopaedics, Leatherhead, United Kingdom) retaining the neck with a proximal hydroxyapatite coating in a series of 52 men (six bilateral) and 40 women (two bilateral), has been described previously. None required revision for aseptic loosening. We have extended the follow-up to 20 years with a minimum of 17 years. The mean age of the patients at total hip replacement was 58.9 years (19 to 84). Six patients were lost to follow-up, but were included up to their last clinical review. A total of 22 patients (22 hips) had died, all from causes unrelated to their surgery. There have been 43 re-operations for failure of the acetabular component. However, in 38 of these the stem was not revised since it remained stable and there was no associated osteolysis. Two of the revisions were for damage to the trunnion after fracture of a modular ceramic head, and in another two, removal of the femoral component was because of the preference of the surgeon. In all cases the femoral component was well fixed, but could be extracted at the time of acetabular revision. In one case both components were revised for deep infection. There has been one case of aseptic loosening of the stem which occurred at 14 years. This stem had migrated distally by 7.6 mm in ten years and 8.4 mm at the time of revision at which stage it was found to be rotationally loose. With hindsight this component had been undersized at implantation. The survivorship for the stem at 17 years with aseptic loosening as the endpoint was 98.6% (95% confidence interval 95.9 to 100) when 62 hips were at risk. All remaining stems had a satisfactory clinical and radiological outcome. The Freeman proximally hydroxyapatite-coated femoral component is therefore a dependable implant and its continued use can be recommended. PMID- 20357322 TI - Charnley low-friction arthroplasty in teenage patients: the ultimate challenge. AB - Increasing follow-up identifies the outcome in younger patients who have undergone total hip replacement (THR) and reveals the true potential for survival of the prosthesis. We identified 28 patients (39 THRs) who had undergone cemented Charnley low friction arthroplasty between 1969 and 2001. Their mean age at operation was 17.9 years (12 to 19) and the maximum follow-up was 34 years. Two patients (4 THRs) were lost to follow-up, 13 (16 THRs) were revised at a mean period of 19.1 years (8 to 34) and 13 (19 THRs) continue to attend regular follow up at a mean of 12.6 years (2.3 to 29). In this surviving group one acetabular component was radiologically loose and all femoral components were secure. In all the patients the diameter of the femoral head was 22.225 mm with Charnley femoral components used in 29 hips and C-stem femoral components in ten. In young patients who require THR the acetabular bone stock is generally a limiting factor for the size of the component. Excellent long-term results can be obtained with a cemented polyethylene acetabular component and a femoral head of small diameter. PMID- 20357323 TI - Total hip replacement in patients with multiple epiphyseal dysplasia with a mean follow-up of 15 years and survival analysis. AB - The hip joint is commonly involved in multiple epiphyseal dysplasia and patients may require total hip replacement before the age of 30 years. We retrospectively reviewed nine patients (16 hips) from four families. The diagnosis of multiple epiphyseal dysplasia was based on a family history, genetic counselling, clinical features and radiological findings. The mean age at surgery was 32 years (17 to 63), with a mean follow-up of 15.9 years (5.5 to 24). Of the 16 hips, ten required revision at a mean of 12.5 years (5 to 15) consisting of complete revision of the acetabular component in three hips and isolated exchange of the liner in seven. No femoral component has loosened or required revision during the period of follow-up. With revision for any reason, the 15-year survival was only 11.4% (95% confidence interval 1.4 to 21.4). However, when considering revision of the acetabular shell in isolation the survival at ten years was 93.7% (95% confidence interval 87.7 to 99.7), reducing to 76.7% (95% confidence interval 87.7 to 98.7) at 15 and 20 years, respectively. PMID- 20357324 TI - Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement: a cause for concern? AB - We measured the plasma 25-hydroxyvitamin D(3) (25(OH)D(3)) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct. PMID- 20357325 TI - Wear-pattern analysis in retrieved tibial inserts of mobile-bearing and fixed bearing total knee prostheses. AB - Components from 73 failed knee replacements (TKRs) consisting of rotating platform, mobile-bearing and fixed-bearing implants were examined to assess the patterns of wear. The patterns were divided into low-grade (burnishing, abrasion and cold flow) and high-grade (scratching, pitting/metal embedding and delamination) to assess the severity of the wear of polyethylene. The rotating platform group had a higher incidence of low-grade wear on the upper surface compared with the fixed-bearing group. By contrast, high-grade wear comprising scratching, pitting and third-body embedding was seen on the lower surface. Linear regression analysis showed a significant correlation of the wear scores between the upper and lower surfaces of the tibial insert (R(2) = 0.29, p = 0.04) for the rotating-platform group, but no significant correlation was found for the fixed-bearing counterpart. This suggests that high-grade wear patterns on the upper surface are reduced with the rotating-platform design. However, the incidence of burnishing, pitting/third-body embedding and scratching wear patterns on the lower surface was higher compared with that in the fixed-bearing knee. PMID- 20357326 TI - Survival and functional outcome after revision of a unicompartmental to a total knee replacement: the New Zealand National Joint Registry. AB - We reviewed the rate of revision of unicompartmental knee replacements (UKR) from the New Zealand Joint Registry between 1999 and 2008. There were 4284 UKRs, of which 236 required revision, 205 to a total knee replacement (U2T) and 31 to a further unicompartmental knee replacement (U2U). We used these data to establish whether the survival and functional outcome for revised UKRs were comparable with those of primary total knee replacement (TKR). The rate of revision for the U2T cohort was four times higher than that for a primary TKR (1.97 vs 0.48; p < 0.05). The mean Oxford Knee Score was also significantly worse in the U2T group than that of the primary TKR group (30.02 vs 37.16; p < 0.01). The rate of revision for conversion of a failed UKR to a further UKR (U2U cohort) was 13 times higher than that for a primary TKR. The poor outcome of a UKR converted to a primary TKR compared with a primary TKR should contra-indicate the use of a UKR as a more conservative procedure in the younger patient. PMID- 20357327 TI - The impact of pre-operative obesity on weight change and outcome in total knee replacement: a prospective study of 529 consecutive patients. AB - We carried out a prospective, continuous study on 529 patients who underwent primary total knee replacement between January 2006 and December 2007 at a major teaching hospital. The aim was to investigate weight change and the functional and clinical outcome in non-obese and obese groups at 12 months post-operatively. The patients were grouped according to their pre-operative body mass index (BMI) as follows: non-obese (BMI < 30 kg/m(2)), obese (BMI (3) 30 to 39 kg/m(2)) and morbidly obese (BMI > 40 kg/m(2)). The clinical outcome data were available for all patients and functional outcome data for 521 (98.5%). Overall, 318 (60.1%) of the patients were obese or morbidly obese. At 12 months, a clinically significant weight loss of > or =5% had occurred in 40 (12.6%) of the obese patients, but 107 (21%) gained weight. The change in the International Knee Society score was less in obese and morbidly obese compared with non-obese patients (p = 0.016). Adverse events occurred in 30 (14.2%) of the non-obese, 59 (22.6%) of the obese and 20 (35.1%) of the morbidly obese patients (p = 0.001). PMID- 20357328 TI - A comparison of early and delayed arthroscopically-assisted reconstruction of the anterior cruciate ligament using hamstring autograft. AB - Delayed rather than early reconstruction of the anterior cruciate ligament is the current recommended treatment for injury to this ligament since it is thought to give a better functional outcome. We randomised 105 consecutive patients with injury associated with chondral lesions no more severe than grades 1 and 2 and/or meniscal tears which only required trimming, to early (< two weeks) or delayed (> four to six weeks) reconstruction of the anterior cruciate ligament using a quadrupled hamstring graft. All operations were performed by a single surgeon and a standard rehabilitation regime was followed in both groups. The outcomes were assessed using the Lysholm score, the Tegner score and measurement of the range of movement. Stability was assessed by clinical tests and measurements taken with the KT-1000 arthrometer, with all testing performed by a blinded uninvolved experienced observer. A total of six patients were lost to follow-up, with 48 patients assigned to the delayed group and 51 to the early group. None was a competitive athlete. The mean interval between injury and the surgery was seven days (2 to 14) in the early group and 32 days (29 to 42) in the delayed group. The mean follow-up was 32 months (26 to 36). The results did not show a statistically significant difference for the Lysholm score (p = 0.86), Tegner activity score (p = 0.913) or the range of movement (p = 1). Similarly, no distinction could be made for stability testing by clinical examination (p = 0.56) and measurements with the KT-1000 arthrometer (p = 0.93). Reconstruction of the anterior cruciate ligament gave a similar clinical and functional outcome whether performed early (< two weeks) or late at four to six weeks after injury. PMID- 20357329 TI - Are extreme distal periprosthetic supracondylar fractures of the femur too distal to fix using a lateral locked plate? AB - It is unclear whether there is a limit to the amount of distal bone required to support fixation of supracondylar periprosthetic femoral fractures. This retrospective multicentre study evaluated lateral locked plating of periprosthetic supracondylar femoral fractures and compared the results according to extension of the fracture distal with the proximal border of the femoral prosthetic component. Between 1999 and 2008, 89 patients underwent lateral locked plating of a supracondylar periprosthetic femoral fracture, of whom 61 patients with a mean age of 72 years (42 to 96) comprising 53 women, were available after a minimum follow-up of six months or until fracture healing. Patients were grouped into those with fractures located proximally (28) and those with fractures that extended distal to the proximal border of the femoral component (33). Delayed healing and nonunion occurred respectively in five (18%) and three (11%) of more proximal fractures, and in two (6%) and five (15%) of the fractures with distal extension (p = 0.23 for delayed healing; p = 0.72 for nonunion, Fisher's exact test). Four construct failures (14%) occurred in more proximal fractures, and three (9%) in fractures with distal extension (p = 0.51). Of the two deep infections that occurred in each group, one resolved after surgical debridement and antibiotics, and one progressed to a nonunion. Extreme distal periprosthetic supracondylar fractures of the femur are not a contra-indication to lateral locked plating. These fractures can be managed with internal fixation, with predictable results, similar to those seen in more proximal fractures. PMID- 20357330 TI - The reverse shoulder prosthesis in the treatment of fractures of the proximal humerus in the elderly. AB - We have previously described the short-term outcome of the use of reverse shoulder arthroplasty in the treatment of acute complex proximal humeral fractures in the elderly. We now report the clinical and radiological outcome of 36 fractures at a mean of 6.6 years (1 to 16). Previously, at a mean follow-up of 6 years (1 to 12) the mean Constant score was 58.5; this was reduced to 53 points with the further follow-up. A total of 23 patients (63%) had radiological evidence of loosening of the glenoid component. Nevertheless, only one patient had aseptic loosening of the baseplate at 12 years' follow-up. The reduction in the mean Constant score with longer follow-up and the further development of scapular notching is worrying. New developments in design, bearing surfaces and surgical technique, and further follow-up, will determine whether reverse shoulder arthroplasty has a place in the management of complex proximal humeral fractures in the elderly. PMID- 20357331 TI - A good outcome following complete injury of the brachial plexus: long-term analysis of the management of two patients. AB - Restoration of hand function is rarely achieved after a complete closed traction lesion of the supraclavicular brachial plexus. We describe the injury, treatment, rehabilitation and long-term results of two patients who regained good function of the upper limb and useful function in the hand after such an injury. Successful repairs were performed within six days of injury. Tinel's sign proved accurate in predicting the ruptures and the distribution of pain was accurate in predicting avulsion. The severe pain that began on the day of injury resolved with the onset of muscle function. Recovery of muscle function preceded recovery of sensation. Recovery of the function of C and Adelta fibres was the slowest of all. PMID- 20357332 TI - Percutaneous anterior transarticular screw fixation for atlantoaxial instability: a case series. AB - We reviewed the outcome of a retrospective case series of eight patients with atlantoaxial instability who had been treated by percutaneous anterior transarticular screw fixation and grafting under image-intensifier guidance between December 2005 and June 2008. The mean follow-up was 19 months (8 to 27). All eight patients had a solid C1-2 fusion. There were no breakages or displacement of screws. All the patients with pre-operative neck pain had immediate relief from their symptoms or considerable improvement. There were no major complications. Our preliminary clinical results suggest that percutaneous anterior transarticulation screw fixation is technically feasible, safe, useful and minimally invasive when using the appropriate instruments allied to intra operative image intensification, and by selecting the correct puncture point, angle and depth of insertion. PMID- 20357333 TI - Micro-decompression for lumbar spinal stenosis: the early outcome using a modified surgical technique. AB - We describe a modified technique of micro-decompression of the lumbar spine involving the use of an operating microscope, a malleable retractor and a high speed burr, which allows decompression to be performed on both sides of the spine through a unilateral, hemi-laminectomy approach. The first 100 patients to be treated with this technique have been evaluated prospectively using a visual analogue score for sciatica and back pain, the MacNab criteria for patient satisfaction, and functional assessment with the Oswestry Disability Index. After a period of follow-up from 12 months to six years and four months, sciatica had improved in 90 patients and back pain in 84 patients. Their result was graded as good or excellent by 82 patients according to the MacNab criteria, and 75 patients had subjective improvement in their walking distance. Late instability developed in four patients. Lumbar micro-decompression has proved to be safe, with few complications. Postoperative instability requiring fusion was uncommon, and less than using traditional approaches in published series. PMID- 20357334 TI - The usefulness of serum amyloid A as a postoperative inflammatory marker after posterior lumbar interbody fusion. AB - The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) mug/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker. PMID- 20357335 TI - The radiological evaluation of acetabular fractures in the elderly. AB - We have examined the accuracy of reduction and the functional outcomes in elderly patients with surgically treated acetabular fractures, based on assessment of plain radiographs and CT scans. There were 45 patients with such a fracture with a mean age of 67 years (59 to 82) at the time of surgery. All patients completed SF-36 questionnaires to determine the functional outcome at a mean follow-up of 72.4 months (24 to 188). All had radiographs and a CT scan within one week of surgery. The reduction was categorised as 'anatomical', 'imperfect', or 'poor'. Radiographs classified 26 patients (58%) as anatomical,13 (29%) as imperfect and six (13%) as poor. The maximum displacement on CT showed none as anatomical, 23 (51%) as imperfect and 22 (49%) as poor, but this was not always at the weight bearing dome. SF-36 scores showed functional outcomes comparable with those of the general elderly population, with no correlation with the radiological reduction. Perfect anatomical reduction is not necessary to attain a good functional outcome in acetabular fractures in the elderly. PMID- 20357336 TI - Complications associated with distraction osteogenesis for infected nonunion of the femoral shaft in the presence of a bone defect: a retrospective series. AB - We undertook a retrospective study of 50 consecutive patients (41 male, 9 female) with an infected nonunion and bone defect of the femoral shaft who had been treated by radical debridement and distraction osteogenesis. Their mean age was 29.9 years (9 to 58) and they had a mean of 3.8 (2 to 19) previous operations. They were followed for a mean of 5.9 years (2.0 to 19.0). The mean duration of the distraction osteogenesis was 24.5 months (2 to 39). Pin-track infection was observed in all patients. The range of knee movement was reduced and there was a mean residual leg-length discrepancy of 1.9 cm (0 to 8) after treatment. One patient required hip disarticulation to manage intractable sepsis. In all, 13 patients had persistent pain. Bony union was achieved in 49 patients at a mean of 20.7 months (12 to 35). Although distraction osteogenesis is commonly used for the treatment of infected femoral nonunion with bone defects, it is associated with a high rate of complications. PMID- 20357337 TI - The reliability and variation of measurements of the os calcis angles in children. AB - The databases of the Picture Archiving and Communication Systems of two hospitals were searched and all children who had a lateral radiograph of the ankle during their attendance at the emergency department were identified. In 227 radiographs, Bohler's and Gissane's angles were measured on two separate occasions and by two separate authors to allow calculation of inter- and intra-observer variation. Intraclass correlation coefficients were used to assess the reliability of the measurements. For Bohler's angle the overall inter-observer reliability, the intraclass correlation coefficient was 0.90 and the intra-observer reliability 0.95, giving excellent agreement. This reliability was maintained across the age groups. For Gissane's angle, inter- and intra-observer reliability was only fair or poor across most age groups. Further analysis of the Bohler's angle showed a significant variation in the mean angle with age. Contrary to published opinion, the angle is not uniformly lower than that of adults but varies with age, peaking towards the end of the first decade before attaining adult values. The age related radiologic changes presented here may help in the interpretation of injuries to the hindfoot in children. PMID- 20357338 TI - Cerebral venous sinus thrombosis following cervical disc arthroplasty. AB - Cerebral venous sinus thrombosis is a rare condition, which is difficult to diagnose. It has not previously been reported following surgery to the cervical spine . We report such a case in a 45-year-old man after cervical disc replacement. A high index of suspicion, with early imaging of the brain and prompt treatment, can produce a favourable outcome, albeit not in this case. PMID- 20357339 TI - Targeted hyperthermia using magnetite cationic liposomes and an alternating magnetic field in a mouse osteosarcoma model. AB - We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45 degrees C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung. PMID- 20357340 TI - Histological evaluation of repair of the rotator cuff in a primate model. AB - The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight 'middle-aged' baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing. PMID- 20357341 TI - Effect of lumbar disc replacement on the height of the disc space and the geometry of the facet joints: a cadaver study. AB - In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charite prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation software applied to CT scans before and after instrumentation. After disc replacement the mean lumbar disc height was doubled (p < 0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p < 0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p < 0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance. PMID- 20357342 TI - Debridement of cartilage lesions before autologous chondrocyte implantation by open or transarthroscopic techniques: a comparative study using post-mortem materials. AB - We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage subchondral bone interface. PMID- 20357343 TI - Dependence of tree ring stable isotope abundances and ring width on climate in Finnish oak. AB - We measured ring widths and isotopic abundances of carbon, oxygen and hydrogen (delta(13)C, delta(18)O and delta(2)H) from the latewood of tree rings of pedunculate oak (Quercus robur L.) in its distributional northern limit in Southern Finland. Ring width was observed to be related to precipitation and relative humidity but not significantly to temperature. delta(13)C and delta(18)O were significantly related to all studied climatic variables, most strongly to cloud cover. Variations in delta(2)H were discovered to be complex combinations of signals from biochemical and physical processes. The results suggest that oaks in Finland can be used as a source of climate information. delta(18)O was discovered to be especially promising as it showed the strongest climate signal and highest common signal between trees. The relationship between climate and ring width indicates that water availability is the main control of ring radial growth. This is supported by the isotope data. High correlation between delta(13)C and delta(18)O time series indicates that photosynthetic carbon assimilation is limited by stomatal control. Therefore, in contrast to the expected temperature limitation, our data indicate that drought limits oak growth more than cold temperatures on the border of its northernmost distribution range. PMID- 20357344 TI - Phenotypic plasticity and local adaptation in leaf ecophysiological traits of 13 contrasting cork oak populations under different water availabilities. AB - Plants distributed across a wide range of environmental conditions are submitted to differential selective pressures. Long-term selection can lead to the development of adaptations to the local environment, generating ecotypic differentiation. Additionally, plant species can cope with this environmental variability by phenotypic plasticity. In this study, we examine the importance of both processes in coping with environmental heterogeneity in the Mediterranean sclerophyllous cork oak Quercus suber. For this purpose, we measured growth and key functional traits at the leaf level in 9-year-old plants across 2 years of contrasting precipitation (2005 and 2006) in a common garden. Plants were grown from acorns originated from 13 populations spanning a wide range of climates along the distribution range of the species. The traits measured were: leaf size (LS), specific leaf area (SLA), carbon isotope discrimination (Delta(13)C) and leaf nitrogen content per unit mass (N(mass)). Inter-population differences in LS, SLA and Delta(13)C were found. These differences were associated with rainfall and temperature at the sites of origin, suggesting local adaptation in response to diverging climates. Additionally, SLA and LS exhibited positive responses to the increase in annual rainfall. Year effect explained 28% of the total phenotypic variance in LS and 2.7% in SLA. There was a significant genotype x environment interaction for shoot growth and a phenotypic correlation between the difference in shoot growth among years and the annual mean temperature at origin. This suggests that populations originating from warm sites can benefit more from wet conditions than populations from cool sites. Finally, we investigated the relationships between functional traits and aboveground growth by several regression models. Our results showed that plants with lower SLA presented larger aboveground growth in a dry year and plants with larger leaf sizes displayed larger growth rates in both years. Overall, the study supports the adaptive value of SLA and LS for cork oak under a Mediterranean climate and their potentially important role for dealing with varying temperature and rainfall regimes through both local adaptation and phenotypic plasticity. PMID- 20357345 TI - First come, first served revisited: factors affecting the same alternative splicing event have different effects on the relative rates of intron removal. AB - Alternative splicing accounts for much of the complexity in higher eukaryotes. Thus, its regulation must allow for flexibility without hampering either its specificity or its fidelity. The mechanisms involved in alternative splicing regulation, especially those acting through coupling with transcription, have not been deeply studied in in vivo models. Much of our knowledge comes from in vitro approaches, where conditions can be precisely controlled at the expense of losing several levels of regulation present in intact cells. Here we studied the relative order of removal of the introns flanking a model alternative cassette exon. We show that there is a preferential removal of the intron downstream from the cassette exon before the upstream intron has been removed. Most importantly, both cis-acting mutations and trans-acting factors that regulate the model alternative splicing event differentially affect the relative order of removal. However, reduction of transcriptional elongation causing higher inclusion of the cassette exon does not change the order of intron removal, suggesting that the assumption, according to the "first come, first served" model, that slow elongation promotes preferential excision of the upstream intron has to be revised. We propose instead that slow elongation favors commitment to exon inclusion during spliceosome assembly. Our results reveal that measuring the order of intron removal may be a straightforward read-out to discriminate among different mechanisms of alternative splice site selection. PMID- 20357346 TI - Writing for the Global Health Promotion audience: Global Health Promotion's niche. PMID- 20357347 TI - The effectiveness of health communication strategies in health education in Kushima, Japan. AB - Japan's 2008 health policy focuses more than ever on health education for behaviour change and outcome measures for physical health status. This is at odds with contemporary health promotion and health education, which frame health as a resource for everyday life and indicate that the evaluation of interventions should measure broader aspects of health rather than just physical aspects. The application of a combination of different health communication models and theories allows for a customized approach, depending on the types of change that are being sought, and can lead to increased relevance as well as a better fit when it comes to evaluating the achievement of broad health promotion goals. This article explores the application of the Outcome Model for Health Promotion to a two-year health education intervention in Kushima, Japan. This model measures program effectiveness from four aspects: physical health outcomes; intermediate health outcomes; health promotion outcomes; and health promotion actions. A quantitative and qualitative longitudinal, mixed model study design and methods were used for the analysis. Data was taken from health exams, structured interviews, and participant observations collected from 67 participants at four times over two years. This intervention relied primarily on health education and communication to achieve mental and social health outcomes more significantly and faster than physical health outcomes. The importance of moving outcome measurement beyond direct health achievements is discussed in light of the relationships between physical, mental, and social health and its determinants, and our results. PMID- 20357348 TI - Policy analysis of oral health promotion in South Africa. AB - This article reports an analysis of oral health promotion in South African health policy. The central aim of this research was to determine the form and coherence of oral health promotion elements within health policies of post-apartheid South Africa. The study set out to test the hypothesis that oral health promotion elements are fully integrated into health policy and programmatic efforts. A conceptual framework was developed to systematically analyse oral health promotion policy and subsequent decision-making across the country at national and provincial levels. The information was drawn from policy documents, protocols and programme plans, complemented by interviews. The results indicate distinct contradictions between the policy formulation process and its impact on health system decision-making. South African health policy was found to be strong on the rhetoric of equity, health promotion, integration and several other features of the Primary Health Care Approach, but showed little evidence of translating this into action. The development and implementation of oral health promotion appears to be dominated by the influence of dental professionals that perpetuate a curative focus on service delivery. There is an urgent need to re-examine the process and content of oral health policy-making in South Africa. The conceptual framework developed for this study could facilitate further research in this area. PMID- 20357349 TI - Network evaluation: principles, structures and outcomes of the German working group of Health Promoting Universities. AB - With more than 60 participating universities, the German working group of Health Promoting Universities (German HPU network) is the largest and most active network of universities as healthy settings. This study aims at evaluating processes and effects of the German HPU network and at supporting the future development of the network. The evaluation was based on the multi faceted network assessment instrument developed by Broesskamp-Stone (7). We used a document analysis, two expert interviews and a survey among members (n = 33) to collect relevant data for the assessment. The analysis showed that the visions of the network can be regarded as fulfilled in most aspects. The members of the network received network support through trustful and mutual relationships. The network ranked high on general network principles like implementation of mutual relationships, sharing of information, risks and resources, equal access to resources, responsibility and consensus orientation. However, a high degree of centralization was found as a negative indicator. Other critical aspects of the network's structures and processes have been the regional predominance of universities from the northern and middle part of Germany, the low representation of students in the network, and the low proportion of members that could successfully implement health promotion into the guiding principles of their university. Overall, the evaluation has shown that the network has worked effectively, has developed meaningful processes and structures and has formulated practical guidelines. Since its 12 years of existence the German HPU network has been able to adapt and to adequately respond to changing contextual conditions regarding health promotion at universities in Germany. The network should develop strategies to counteract the critical aspects and detected imbalances in order to further increase its impact on universities as healthy settings. PMID- 20357350 TI - The sirens' song of empowerment: a case study of health promotion and the New Zealand Prostitutes Collective. AB - The New Zealand Prostitutes Collective (NZPC) formed in 1987 with the intention of reforming the policy that governed prostitution. The Prostitution Reform Act 2003 was created to protect sex workers from exploitation and to give them the same rights as other workers by protecting their occupation health and safety. It is an example of community empowerment in which a small and relatively powerless group of women strived to achieve social justice and equity for all sex workers. This article provides, for the first time, the story of how the NZPC was not only able to decriminalize prostitution but also to form a framework that safeguarded the rights of all sex workers in New Zealand. It is a fascinating case study that provides insightful information into how one civil society group had a direct influence on public policy. The implications of the case study to health promotion practice are discussed and will be of interest to planners and practitioners involved in the strengthening of community empowerment. PMID- 20357351 TI - Sustainability of community-capacity to promote safer motherhood in northwestern Tanzania: what remains? AB - OBJECTIVE: To examine the remains of the Community-Based Reproductive Health Project (CBRHP) implemented by CARE-Tanzania to address high maternal mortality in two rural districts. METHODS: In early 2007, data were collected from 29 villages and used to assess sustainability of emergency transport systems, retention of village health workers (VHWs), and their potential impact on maternal health. Surveillance data from the Ministry of Health were reviewed to assess changes in prenatal and service use indicators. RESULTS: From 2001 through 2006, the CBRHP-trained VHWs have continued to provide education and referrals to women in their communities including prenatal and emergency obstetric care; six villages with emergency transport systems have continued for more than 5 years providing free or low-cost transport to health facilities. Selected maternal and infant health indicators, such as early prenatal care, identification of pregnancy-related danger signs, and data on maternal and infant outcomes, improved in the two targeted districts over time. CONCLUSIONS: The two components of CBRHP, work of VHWs and community-financing for emergency transport systems in six villages, have continued. Both of these promote maternal health and linkages with the health delivery systems. Surveillance data show changes in maternal health indicators that were targeted by the district-wide CBRHP interventions. Programs such as CBRHP, with focus on capacity-building and empowerment, can assist in mobilizing the formal and informal systems in communities, components of which may be sustained over time. PMID- 20357352 TI - The uncompassionate elements of the Compassionate Care Benefits Program: a critical analysis. AB - Palliative care is a heavy burden to many Canadians who have dying relatives or friends. The Canadian government implemented a sub-program under the Employment Insurance - Compassionate Care Benefits Program (CCBs) to financially assist informal end-of-life caregivers (1). Since the current Employment Insurance Program's regulations pose a number of barriers for non-standard employees, many informal caregivers are automatically excluded from its sub-program; the CCBs program. This is especially true for those who belong to disadvantaged social groups, and women. This article explores whether a program designed as part of Employment Insurance can provide comprehensive support to those informal end-of life care-givers, and whether it is equally accessible to all Canadians. The authors argue that, in order to make the CCBs program effective, it needs to be made independent from Canada's Employment Insurance Program and hence become a true compassionate program that supports all the informal caregivers equally. PMID- 20357353 TI - Building capacity in workplace health promotion: the case of the Healthy Together e-learning project. AB - The current global economic crisis poses major challenges for workplace health promotion (WHP). Activities that are not perceived to obviously and directly contribute to profits could be sacrificed. This paper argues that WHP must remain centre-stage because of the rights of workers to a healthy, safe working environment but also because of WHP's beneficial financial implications for enterprises. Capacity building for WHP can be developed even within a recessionary environment, particularly if the focus is on the wider workforce, described here as people for whom workplace health promotion may not be their primary function but who have an important role to play in health improvement in workplaces. There is a strong case for the development of the wider workforce based both on the lack of suitably qualified specialists and on the practicalities of having WHP implemented within organizations, particularly for small and medium-sized enterprises (SMEs). SMEs make up a very significant proportion of the global economy and are identified as a priority area for action internationally. An example of an e-learning course, the Healthy Together programme, developed by a partnership of three countries, is discussed as an approach that has potential to develop capacity for WHP in the current climate. The findings of the evaluation of the Healthy Together programme indicate that there is a real potential in developing e-learning materials for training those with a brief for promoting workplace health and safety in SMEs. Although modifications in some aspects of delivery identified in the evaluation of the pilot course need to be considered, the course was well received, and was reported to be relevant to the learning needs of students, to their workplaces and specifically to small businesses in rural areas. Specific features of the e learning approach increase its potential to address capacity building for WHP. PMID- 20357354 TI - Tackling health determinants in rural India: the KHOJ initiative. AB - There have been significant public health achievements in recent years; not only do people live longer and healthier lives, but there has also been a decline in communicable diseases, like tuberculosis, and water-borne diseases, especially in developing countries like India. Although lifestylerelated problems are emerging globally, developing countries carry heavier burdens of poor health conditions, which is an issue of serious concern, in particular among marginalized populations. Reaching out to these groups is a global challenge, and particularly in India, where one-third of the population (between 250 and 300 million people) live in remote, difficult and vulnerable areas lacking basic amenities. In order to address the 'health for all' challenge, this Commentary advocates for the public, private and non-profit sectors to work together to implement innovative community-based approaches that address the various social determinants of health. The case of the Voluntary Health Association of India (VHAI), a national NGO, is presented as an example of successful coordinated community and policy actions to improve health determinants in remote rural areas of India. PMID- 20357355 TI - Health inequalities in the Caribbean: increasing opportunities and resources. AB - Social inequalities in health are not a priority in the Caribbean region. However, a few studies suggested such disparities and indicators show important socioeconomic disparities between and within countries. There are indications that governments' investment in health and other social programs is insufficient in the region and that regional health institutions that guide national health policies and programs do not make the reduction of social inequalities a priority. Furthermore, the public health sector is generally weak and health services are mainly focusing on curative services. The author argues that there is a need to develop and to implement social policies that include equity and social justice as core values. In order to increase the focus on health inequalities in the region, there is also a need to strengthen the Public Health field that integrates Health Promotion strategies. It is also suggested that international, regional and national health sectors that include academic and research institutions, health-related journals and associations, and non governmental organizations put health inequalities in the Caribbean on their agenda. Furthermore, there should be a fundamental switch from a biomedical perspective of health to a paradigm that considers health as the expression of political, social and economic circumstances. PMID- 20357356 TI - A health promotion approach to addressing health equity. PMID- 20357358 TI - [Prevention and reduction of health inequities: a difficult conciliation]. PMID- 20357360 TI - Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. AB - OBJECTIVE: Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity. RESEARCH DESIGN AND METHODS: Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c(+)CD206(+) cells in "crown" aggregates and solitary CD11c(-)CD206(+) cells at adipocyte junctions. In obese women, CD11c(+) ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c(+) ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1beta, -6, -8, and -10; tumor necrosis factor-alpha; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c(+) ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c(-) ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c(+) ATMs, but not CD11c(-) ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes. CONCLUSIONS: These findings identify proinflammatory CD11c(+) ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c(+) ATMs indicates they metabolize lipid and may initiate adaptive immune responses. PMID- 20357361 TI - Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers. AB - OBJECTIVE: Type 1 diabetes results from selective T-cell-mediated destruction of the insulin-producing beta-cells in the pancreas. In this process, islet epitope specific CD8(+) T-cells play a pivotal role. Thus, monitoring of multiple islet specific CD8(+) T-cells may prove to be valuable for measuring disease activity, progression, and intervention. Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive. RESEARCH DESIGN AND METHODS: Here, we used a combinatorial quantum dot major histocompatibility complex multimer technique to simultaneously monitor the presence of HLA-A2 restricted insulin B(10-18), prepro-insulin (PPI)(15-24), islet antigen (IA)-2(797-805), GAD65(114-123), islet-specific glucose-6 phosphatase catalytic subunit-related protein (IGRP)(265-273), and prepro islet amyloid polypeptide (ppIAPP)(5-13)-specific CD8(+) T-cells in recent-onset diabetic patients, their siblings, healthy control subjects, and islet cell transplantation recipients. RESULTS: Using this kit, islet autoreactive CD8(+) T cells recognizing insulin B(10-18), IA-2(797-805), and IGRP(265-273) were shown to be frequently detectable in recent-onset diabetic patients but rarely in healthy control subjects; PPI(15-24) proved to be the most sensitive epitope. Applying the "Diab-Q-kit" to samples of islet cell transplantation recipients allowed detection of changes of autoreactive T-cell frequencies against multiple islet cell-derived epitopes that were associated with disease activity and correlated with clinical outcome. CONCLUSIONS: A kit was developed that allows simultaneous detection of CD8(+) T-cells reactive to multiple HLA-A2-restricted beta-cell epitopes requiring limited amounts of blood, without a need for in vitro culture, that is applicable on stored blood samples. PMID- 20357363 TI - Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. AB - OBJECTIVE: Brown adipose tissue (BAT) regulates energy homeostasis and fat mass in mammals and newborns and, most likely, in adult humans. Because BAT activity and BAT mass decline with age in humans, the impact of BAT on adiposity may decrease with aging. In the present study we addressed this hypothesis and further investigated the effect of age on the sex differences in BAT activity and BAT mass. RESEARCH DESIGN AND METHODS: Data from 260 subjects (98 with BAT and 162 study date-matched control subjects) who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) under thermoneutral conditions were analyzed. BAT activity and BAT mass were determined in the upper body. RESULTS: BAT activity and BAT mass were higher in female (1.59 +/- 0.10 and 32 +/- 5 g vs. 1.02 +/- 0.10 and 18 +/- 4 g, both P < or = 0.0006) than in male subjects. In multivariate analyses, sex (P < 0.0001), age (P < 0.0001), and BMI (P = 0.0018) were associated independently with BAT activity. Interestingly, only in male subjects was there an interaction between BMI and age in determining BAT activity (P = 0.008) and BAT mass (P = 0.0002); BMI decreased with increasing BAT activity and BAT mass in the lowest age tertile (Spearman rank correlation coefficient r(s) = -0.38, P = 0.015 and r(s) = -0.37, P = 0.017, respectively), not in the higher age tertiles. Furthermore, BAT activity and mass differed between female and male subjects only in the upper two age tertiles (all P < or = 0.09). CONCLUSIONS: Our data corroborate that, in general, BAT activity and BAT mass are elevated in female subjects and in younger people. Importantly, we provide novel evidence that the impact of BAT activity and BAT mass on adiposity appears to decline with aging only in male subjects. Furthermore, while BAT activity and BAT mass only moderately decline with increasing age in female subjects, a much stronger effect is found in male subjects. PMID- 20357362 TI - Pituitary adenylate cyclase-activating polypeptide stimulates glucose production via the hepatic sympathetic innervation in rats. AB - OBJECTIVE: The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). RESEARCH DESIGN AND METHODS: Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. RESULTS: Intracerebroventricular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. CONCLUSIONS: This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production. PMID- 20357364 TI - Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content. AB - OBJECTIVE: Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. RESEARCH DESIGN AND METHODS: We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 +/- 8.9 years, BMI 33.8 +/- 4 kg/m(2)). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test. RESULTS: For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = -0.27, P < 0.05), and visceral (r = 0.25, P < 0.05) and total fat mass (r = -0.32, P < 0.05), but not to intramyocellular lipids (r = -0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r(2) = -0.43, P < 0.01, r(2) = -0.34, and r(2) = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. CONCLUSIONS: Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction. PMID- 20357365 TI - Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. AB - OBJECTIVE: The hormone fibroblast growth factor 21 (FGF21) exerts diverse, beneficial effects on energy balance and insulin sensitivity when administered systemically to rodents with diet-induced obesity (DIO). The current studies investigate whether central FGF21 treatment recapitulates these effects. RESEARCH DESIGN AND METHODS: After preliminary dose-finding studies, either saline vehicle or recombinant human FGF21 (0.4 microg/day) was infused continuously for 2 weeks into the lateral cerebral ventricle of male Wistar rats rendered obese by high fat feeding. Study end points included measures of energy balance (body weight, body composition, food intake, energy expenditure, and circulating and hepatic lipids) and glucose metabolism (insulin tolerance test, euglycemic hyperinsulinemic clamp, and hepatic expression of genes involved in glucose metabolism). RESULTS: Compared with vehicle, continuous intracerebroventricular infusion of FGF21 increased both food intake and energy expenditure in rats with DIO, such that neither body weight nor body composition was altered. Despite unchanged body fat content, rats treated with intracerebroventricular FGF21 displayed a robust increase of insulin sensitivity due to increased insulin induced suppression of both hepatic glucose production and gluconeogenic gene expression, with no change of glucose utilization. CONCLUSIONS: FGF21 action in the brain increases hepatic insulin sensitivity and metabolic rate in rats with DIO. These findings identify the central nervous system as a potentially important target for the beneficial effects of FGF21 in the treatment of diabetes and obesity. PMID- 20357366 TI - PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans. AB - OBJECTIVE: Peptide YY(3-36) (PYY(3-36)), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY(3-36) and oxyntomodulin can be additive. RESEARCH DESIGN AND METHODS: Twelve overweight or obese human volunteers underwent a randomized, double-blinded, placebo-controlled study. An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY(3-36) or oxyntomodulin or combined PYY(3-36)/oxyntomodulin. RESULTS: Energy intake during coadministration of PYY(3-36) and oxyntomodulin was reduced by 42.7% in comparison with the saline control and was significantly lower than that during infusions of either hormone alone. CONCLUSIONS: The anorectic effects of PYY(3 36) and oxyntomodulin can be additive in overweight and obese humans. Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity. PMID- 20357367 TI - Racial disparities in health status: a comparison of the morbidity among American Indian and U.S. adults with diabetes. AB - OBJECTIVE: American Indians and Alaska Natives are 2.3 times more likely to have diabetes than are individuals in the U.S. general population. The objective of this study was to compare morbidity among American Indian and U.S. adults with diabetes. RESEARCH DESIGN AND METHODS: We extracted demographic and health service utilization data for an adult American Indian population aged 18-64 years (n = 30,121) served by the Phoenix Service Unit from the Indian Health Service clinical reporting system. Similar data for a U.S. population (n = 1,500,002) with commercial health insurance, matched by age and sex to the American Indian population, were drawn from the MartketScan Research Database. We used Diagnostic Cost Groups to identify medical conditions for which each individual was treated and to assign a risk score to quantify his or her morbidity burden. We compared the prevalence of comorbidities and morbidity burden of American Indian and U.S. adults with diabetes. RESULTS: American Indians with diabetes had significantly higher rates of hypertension, cerebrovascular disease, renal failure, lower extremity amputations, and liver disease than commercially insured U.S. adults with diabetes (P < 0.05). The American Indian prevalence rates were 61.2, 6.9, 3.9, 1.8, and 7.1%, respectively. The morbidity burden among the American Indian with diabetes exceeded that of the insured U.S. adults with diabetes by 50%. CONCLUSIONS: The morbidity burden associated with diabetes among American Indians seen at the Phoenix Service Unit far exceeded that of commercially insured U.S. adults. These findings point to the urgency of enhancing diabetes prevention and treatment services for American Indians/Alaska Natives to reduce diabetes-related disparities. PMID- 20357368 TI - Estimated average glucose and self-monitored mean blood glucose are discordant estimates of glycemic control. AB - OBJECTIVE: The A1C-Derived Average Glucose study recommended reporting A1C in estimated average glucose (eAG) equivalents. We compared eAG with self-monitored mean blood glucose (MBG) to determine whether eAG is systematically biased due to biological variation in the relationship between MBG and A1C. RESEARCH DESIGN AND METHODS: MBG and A1C were recorded from charts of 202 pediatric type 1 diabetic patients at 1,612 clinic visits. Patients were divided into groups with low, moderate, or high A1C bias based on a hemoglobin glycation index (HGI). RESULTS: The mean +/- SD values for MBG versus eAG were as follows: total population, 194 +/- 34 vs. 196 +/- 36 mg/dl; low-HGI group, 186 +/- 31 vs. 163 +/- 20 mg/dl; moderate-HGI group, 195 +/- 28 vs. 193 +/- 19 mg/dl; and high-HGI group, 199 +/- 42 vs. 230 +/- 31 mg/dl. CONCLUSIONS: eAG underestimated MBG in low HGI patients and overestimated MBG in high HGI patients. Disagreement between eAG and MBG downloaded from patient glucose meters will cause confusion if eAG is implemented for clinical use. PMID- 20357369 TI - No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes. AB - OBJECTIVE: To determine whether daily intake of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is safe and improves beta-cell function in patients with recently diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS: Safety was assessed in an open study of 25 patients aged 18-39 years with recent-onset type 1 diabetes who received 0.25 microg 1,25(OH)(2)D(3) daily for 9 months. An additional 40 patients were randomly assigned to 0.25 microg 1,25(OH)(2)D(3) or placebo daily for 9 months and followed for a total of 18 months for safety, beta cell function, insulin requirement, and glycemic control. RESULTS: Safety assessment showed values in the normal range in nearly all patients, regardless of whether they received 1,25(OH)(2)D(3) or placebo. No differences in AUC C peptide, peak C-peptide, and fasting C-peptide after a mixed-meal tolerance test between the treatment and placebo groups were observed at 9 and 18 months after study entry, with approximately 40% loss for each parameter over the 18-month period. A1C and daily insulin requirement were similar between treatment and placebo groups throughout the study follow-up period. CONCLUSIONS: Treatment with 1,25(OH)(2)D(3) at a daily dose of 0.25 microg was safe but did not reduce loss of beta-cell function. PMID- 20357370 TI - A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess. AB - OBJECTIVE: Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. RESEARCH DESIGN AND METHODS: We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry. RESULTS: Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1 year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005). CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine metabolic profile improve most with metformin therapy. PMID- 20357371 TI - Dose-response effects of insulin glargine in type 2 diabetes. AB - OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 +/- 3 years, with BMI 36 +/- 2 kg/m(2) and A1C 8.3 +/- 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique. RESULTS Glargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and beta-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 mumol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal. CONCLUSION: A single subcutaneous injection of glargine at a dose of >or=0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes. PMID- 20357372 TI - Further improvement in postprandial glucose control with addition of exenatide or sitagliptin to combination therapy with insulin glargine and metformin: a proof of-concept study. AB - OBJECTIVE: To assess the effect of a 4-week adjunctive therapy of exenatide (EXE) (5-10 microg b.i.d.) or sitagliptin (SITA) (100 mg once daily) in response to a standardized breakfast meal challenge in 48 men or women with type 2 diabetes receiving insulin glargine (GLAR) + metformin (MET). RESEARCH DESIGN AND METHODS: This was a single-center, randomized, open-label, active comparator-controlled study with a three-arm parallel group design, consisting of: screening, 4- to 8 week run-in period, 4-week treatment period, and follow-up. In all three groups, the GLAR dose was titrated according to an algorithm (fasting blood glucose 40 mg/24 h sustained for >or=1 year in normoalbuminuric individuals. RESULTS In a mean follow-up of 6.5 years, we observed a lower mean UAER (difference 22.7 mg/24 h [95% CI 1.6-43.8)]) in the top versus the bottom third of dietary n-3 LC-PUFAs, but we found no association with incident albuminuria. CONCLUSIONS: Dietary n-3 LC-PUFAs appear inversely associated with the degree but not with the incidence of albuminuria in type 1 diabetes. These findings require further investigation in prospective studies. PMID- 20357377 TI - Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial. AB - OBJECTIVE: To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer. RESEARCH DESIGN AND METHODS: Forty-five adult diabetic patients with nonischemic, noninfected neuropathic plantar ulcer were randomly assigned for treatment with a nonremovable fiberglass off-bearing cast (total contact cast [TCC] group) or walker cast (Stabil-D group). Treatment duration was 90 days. Percent reduction in ulcer surface area and total healing rates were evaluated after treatment. RESULTS: A total of 48 patients were screened; however, 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts. There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study. Ulcer surface decreased from 1.41 to 0.21 cm(2) (P < 0.001) in the TCC group and from 2.18 to 0.45 cm(2) (P < 0.001) in the Stabil-D group, with no significant differences between groups (P = 0.722). Seventeen patients (73.9%) in the TCC group and 16 patients (72.7%) in the Stabil-D group achieved healing (P = 0.794). Average healing time was 35.3 +/- 3.1 and 39.7 +/- 4.2 days in the TCC and Stabil-D group, respectively (P = 0.708). CONCLUSIONS: The Stabil D cast walker, although removable, was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate. The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers. PMID- 20357379 TI - Psychosocial well-being and functional outcomes in youth with type 1 diabetes 12 years after disease onset. AB - OBJECTIVE: Type 1 diabetes in youth and community controls were compared on functional outcomes. Relationships were examined between psychosocial variables at diagnosis and functional outcome 12 years later. RESEARCH DESIGN AND METHODS: Participants were subjects with type 1 diabetes (n = 110, mean age 20.7 years, SD 4.3) and control subjects (n = 76, mean age 20.8 years, SD 4.0). The measures used included the Youth Self-Report and Young Adult Self-Report and a semi structured interview of functional outcomes. Type 1 diabetes participants also provided information about current diabetes care and metabolic control from diagnosis. RESULTS: Type 1 diabetes participants and control subjects reported similar levels of current well-being but for the youth with type 1 diabetes, the mental health referral rates over the previous 12 years were higher by 19% and school completion rates were lower by 17%. Over one-third of clinical participants were not currently receiving specialist care and this group had higher mental health service usage in the past (61 vs. 33%) and lower current psychosocial well- being. Within the type 1 diabetes group, behavior problems, high activity, and low family cohesion at diagnosis predicted lower current well being, but were not associated with metabolic control history. Poorer metabolic control was associated with higher mental health service usage. CONCLUSIONS: Type 1 diabetes participants report similar levels of current psychosocial well-being compared with control subjects, but higher levels of psychiatric morbidity since diagnosis and lower school completion rates. Psychiatric morbidity was associated with poor metabolic control and failure to transition to tertiary adult diabetes care. PMID- 20357380 TI - Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. AB - OBJECTIVE: Growth deferentiation factor-15 (GDF-15) is involved in inflammation and apoptosis. Expression is induced in the heart in response to ischemia and in atherosclerotic plaques. The aim of this study was to investigate GDF-15 levels in relation to all-cause mortality, cardiovascular mortality and morbidity, decline in glomerular filtration rate (GFR), and progression toward end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: The study was a prospective observational follow-up study including 451 type 1 diabetic patients with diabetic nephropathy (274 men, aged 42.1 +/- 0.5 years [means +/- SD], diabetes duration 28.3 +/- 8.9 years, GFR 76 +/- 33 ml/min/1.73 m(2)) and a control group of 440 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men, aged 45.4 +/- 11.5 years, duration of diabetes 27.7 +/- 10.1 years). The patients were followed for 8.1 (0.0-12.9) years (median [range]). RESULTS: Among normoalbuminuric patients, GDF-15 above the median predicted an adjusted (age, systolic blood pressure [sBP], and estimated GFR) increased risk of all cause mortality (hazard ratio [HR] 3.6 [95% CI 1.3-10.3]; P = 0.014). Among patients with diabetic nephropathy, higher (fourth quartile) versus lower (first quartile) GDF-15 levels predict all-cause mortality (covariate-adjusted [sex, age, smoking, blood pressure, A1C, cholesterol, GFR, N-terminal prohormone B-type natriuretic peptide, antihypertensive treatment, and previous cardiovascular events]; HR 4.86 [95% CI 1.37-17.30]) as well as fatal and nonfatal cardiovascular events (adjusted HR 5.59 [1.23-25.43] and 3.55 [1.08-11.64], respectively). In addition, higher GDF-15 levels predict faster decline in GFR (P < 0.001) but not development of ESRD. CONCLUSIONS: Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function. PMID- 20357381 TI - Partial sleep restriction decreases insulin sensitivity in type 1 diabetes. AB - OBJECTIVE: Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied seven patients (three men, four women) with type 1 diabetes: mean age 44 +/- 7 years, BMI 23.5 +/- 0.9 kg/m(2), and A1C 7.6 +/- 0.3%. They were studied once after a night of normal sleep duration and once after a night of only 4 h of sleep. Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with an infusion of [6,6-(2)H(2)]glucose. RESULTS Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (469 +/- 8.5 vs. 222 +/- 7.1 min, P = 0.02). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids (NEFAs), or endogenous glucose production. Endogenous glucose production during the hyperinsulinemic clamp was not altered during the night of sleep restriction compared with the night of unrestricted sleep (6.2 +/- 0.8 vs. 6.9 +/- 0.6 micromol x kg lean body mass(-1) x min(-1), NS). In contrast, sleep restriction decreased the glucose disposal rate during the clamp (25.5 +/- 2.6 vs. 22.0 +/- 2.1 micromol x kg lean body mass(-1) x min(-1), P = 0.04), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 21% (P = 0.04). Sleep restriction did not alter plasma NEFA levels during the clamp (143 +/- 29 vs. 133 +/- 29 micromol/l, NS). CONCLUSIONS: Partial sleep deprivation during a single night induces peripheral insulin resistance in these seven patients with type 1 diabetes. Therefore, sleep duration is a determinant of insulin sensitivity in patients with type 1 diabetes. PMID- 20357382 TI - Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non ST elevation acute coronary syndrome. AB - OBJECTIVE: We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris. RESEARCH DESIGN AND METHODS: Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software. RESULTS: In patients with diabetes and A1C of >or=8-10% at randomization (n = 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI -1.4 to -1.0), and the placebo-adjusted (n = 182) decrease in A1C by ranolazine was 0.59% (95% CI -0.99 to -0.20, P < 0.001). In patients with FPG of 150-400 mg/dl at randomization, ranolazine (n = 131) compared with placebo (n = 147) reduced FPG by 25.7 mg/dl (95% CI -43.3 to -8.1, P = 0.001). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P = 0.046; FPG, P < 0.001), indicating that lowering of A1C and FPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina. CONCLUSIONS: Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes. PMID- 20357384 TI - Assessment of coronary plaque burden by computed tomography: getting closer--step by step. PMID- 20357383 TI - Glycemic control, coping, and internalizing and externalizing symptoms in adolescents with type 1 diabetes: a cross-lagged longitudinal approach. AB - OBJECTIVE: This study examines how active coping and withdrawal, psychological (internalizing and externalizing) symptoms, and glycemic control (A1C values) influence each other across time in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: One hundred and nine adolescents participated in a four-wave longitudinal study spanning four years (mean age at Time 1 was 13.77). Patients were visited at home and completed questionnaires measuring coping and psychological symptoms. The treating physicians were contacted to obtain A1C values. Cross-lagged path analysis from a structural equation modeling approach was used for data analysis. RESULTS: Clinically meaningful pathways between coping and glycemic control were found across time. Active coping prospectively predicted lower A1C levels, which, in turn, predicted active coping. Higher A1C levels and higher psychological symptoms consistently predicted avoidance coping across time. Finally, psychological symptomatology constituted an important link in the observed longitudinal chain of effects. More specifically, higher A1C values and symptomatology at Time 1 positively predicted withdrawal at Time 2, which, in turn, positively predicted symptomatology at Time 3. Next, symptomatology at Time 3 positively predicted higher A1C values at Time 4, thus coming full circle. CONCLUSIONS: Coping with everyday stress, psychological symptoms, and glycemic control were interrelated across time. Evidence was obtained for reciprocal pathways and mutually reinforcing mechanisms, indicating the need to monitor coping strategies and psychological symptoms along with glycemic control in optimizing clinical care in adolescents with type 1 diabetes. PMID- 20357385 TI - To ventilate or not to ventilate during cardiopulmonary resuscitation: that is the question. PMID- 20357386 TI - Subcutaneous abdominal adipose tissue is associated with the metabolic syndrome in Asian Indians independent of intra-abdominal and total body fat. AB - HYPOTHESIS: Subcutaneous abdominal adipose tissue (SCAT) compared with intra abdominal adipose tissue (IAAT) would be more significantly associated with the metabolic syndrome in Asian Indians. DESIGN: Cross-sectional study. SETTING: Tertiary care medical institution. SUBJECTS: 100 healthy adults without known heart disease or diabetes. INTERVENTIONS: Magnetic resonance imaging to measure cross-sectional areas of abdominal adipose tissue compartments at the L3-L4 intervertebral level. Dual energy x-ray absorptiometry to measure fat percentage (BF%) and lean mass of total body, trunk, legs and arms. RESULTS: Subjects with the metabolic syndrome (n=35) had a significantly higher BF%, SCAT and IAAT than those without it. Both SCAT and IAAT showed a significant correlation with blood pressure and triglycerides. One SD increase in IAAT (odds ratio (OR) 3.43; 95% CI 1.78 to 6.63) or SCAT area (OR 6.35; 95% CI 2.75 to 14.7) was significantly associated with the metabolic syndrome. On comparing them in the same model, SCAT was the only significant factor associated with the metabolic syndrome (OR 4.92; 95% CI, 1.95 to 12.38). In receiver operating characteristic curve analysis, significant areas under the curves (AUC) were noted for IAAT (0.77) and SCAT (0.89). On comparing the equality of AUC by C statistics, SCAT was a more significant predictor of the metabolic syndrome than IAAT (p=0.009). Only SCAT was significantly associated with the metabolic syndrome after adjusting for BF%, lean body mass or trunk lean mass. CONCLUSION: SCAT is a more important predictor of the metabolic syndrome in Asian Indians than IAAT. The significance of SCAT in the pathogenesis of atherosclerosis and diabetes needs to be investigated further in Asian Indians. PMID- 20357387 TI - Is direct stenting superior to stenting with predilation in patients treated with percutaneous coronary intervention? Results from a meta-analysis of 24 randomised controlled trials. AB - BACKGROUND: In the last decade, direct stenting has been proposed as an alternative strategy to conventional stenting with balloon predilation. The aim of this study was to perform a meta-analysis of randomised trials comparing a direct stenting strategy versus a conventional one. METHODS: A literature search was performed using Medline, EMBASE, the Cochrane Central Register of Controlled Trials, scientific session abstracts and relevant websites, from inception of each database to June 2009. Included studies comprised randomised controlled trials evaluating direct versus conventional stenting in patients undergoing percutaneous coronary intervention. Primary endpoint was the composite of death or myocardial infarction and secondary endpoints were myocardial infarction and target-vessel revascularisation occurrence. RESULTS: 24 trials met inclusion criteria, with 6803 patients enrolled (3412 or 50.15% randomised to direct stenting and 3391 or 49.85% randomised to conventional stenting). Up to 6-month follow-up, the composite of death or myocardial infarction was significantly reduced with direct stenting compared with conventional stenting (3.95% versus 5.10% respectively, OR=0.76 (95% CI 0.60 to 0.96), p=0.02). This reduction was primarily driven by a lower myocardial infarction occurrence (3.16% versus 4.04%, respectively, OR=0.77 (0.59 to 0.99), p=0.04). Furthermore, direct stenting was not associated with a reduction in target-vessel revascularisation (6.50% versus 6.96%, respectively, OR=0.92 (0.76 to 1.12), p=0.42). CONCLUSION: This meta analysis demonstrates that, in selected coronary lesions, direct stenting improves outcome in patients undergoing percutaneous coronary intervention, primarily reducing myocardial infarction incidence. PMID- 20357388 TI - Is there benefit in implanting defibrillators in patients with severe heart failure? AB - BACKGROUND: It is current practice to withhold implantable cardioverter defibrillators (ICD) from patients with severe heart failure because their deaths are judged as non-sudden and therefore assumed not to be preventable by ICD. If this was true, there should be a trend towards reduced preventability of deaths in the severe heart failure subgroups within existing randomised control ICD trials. We tested the prevailing assumption that patients with most severe heart failure would not benefit from ICD implantation. METHODS Six trials were identified enrolling 7873 patients, with 2734 patients randomly assigned to receive an ICD. Reduction in mortality in the ICD arm varied between 5.6% and 31%. All six trials provided data separated into higher and lower ejection fraction subgroups. Five trials provided data separated into higher and lower New York Heart Association (NYHA) class patient subgroups. RESULTS: For patients subcategorised by NYHA class, there was a non-significant difference in z-score (p=0.922) between patients with mild to moderate and severe heart failure. Similarly, subgrouping by left ventricular ejection fraction (LVEF) revealed no significant difference between z-scores (p=0.170). Both observations suggest no attenuation of benefit of ICD implantation in patients with higher NYHA class or lower LVEF. CONCLUSION: There is no evidence within the existing trial populations of a tendency for the relative risk reduction to be smaller in patients with severe heart failure. The prevailing assumption that severe heart failure patients are less likely to benefit from ICD therapy must be questioned. PMID- 20357389 TI - 22q11.2 Deletion Syndrome is under-recognised in adult patients with tetralogy of Fallot and pulmonary atresia. AB - BACKGROUND: Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice to test all children with typical CHD for 22q11.2DS, many adult patients have not been tested in the past and therefore 22q11.2DS might be under-recognised in adults. OBJECTIVES: To determine the prevalence of 22q11.2DS in adults with tetralogy of Fallot (TOF) and pulmonary atresia (PA)/ventricular septal defect (VSD) and to assess the level of recognition of the syndrome in adult patients. METHODS: Patients were identified from CONCOR, a nationwide registry for adult patients with CHD. Inclusion criteria were diagnosis of TOF or PA/VSD and the availability of DNA. Patients with syndromes other than 22q11.2DS were excluded. Multiplex ligation-dependent probe amplification was used to detect 22q11.2 microdeletions. RESULTS: 479 patients with TOF and 79 patients with PA/VSD (56% male, median age 34.7 years) were included and analysed. Twenty patients were already known to have 22q11.2DS. A 22q11.2 microdeletion was detected in a further 24 patients. Thirty-one patients with TOF (6.5%) had 22q11.2DS, whereas 13 patients with PA/VSD had 22q11.2DS (16.5%). Of all 22q11.2 microdeletions, 54% (24/44) were unknown before this study. CONCLUSION: This study shows that although the prevalence of 22q11.2DS in adults with TOF and PA/VSD is substantial, it is unrecognised in more than half of patients. As the syndrome has important clinical and reproductive implications, a diagnostic test should be considered in all adult patients with TOF and PA/VSD. PMID- 20357390 TI - Percutaneous closure of hypertensive ductus arteriosus. AB - BACKGROUND: The Amplatzer duct occluder (ADO) has been used with success to close large patent ductus arteriosus (PDA), but some problems exist especially with hypertensive PDAs, such as incomplete closure, haemolysis, left pulmonary artery stenosis, obstruction of the descending aorta and progressive pulmonary vascular disease. METHODS AND RESULTS: We analysed a group of 168 patients with isolated PDA and pulmonary artery systolic pressure (PSAP) > or =50 mm Hg. Mean age was 10.3 +/- 14.3 years (median 3.9), PDA diameter was 6.4 +/- 2.9 mm (median 5.9), PASP was 63.5 +/- 16.2 mm Hg (median 60), Qp/Qs was 2.7 +/- 1.2 (median 2.5), total pulmonary resistance index (PRI) was 3.69 +/- 2.15 (median 3.35) and vascular PRI was 2.73 +/- 1.72 (median 2.37). We used ADOs in 145 (86.3%) cases, Amplatzer muscular ventricular septal defect occluders (AMVSDO) in 18 (10.7%), Amplatzer septal occluders (ASO) in three (1.8%) and the Gianturco-Grifka device in two (1.2%) cases. Device diameter was 106.3% +/- 51% higher than PDA diameter. PASP decreased after occlusion to 42.5 +/- 13.3 mm Hg (p<0.00001). Immediately after closure, no or trivial shunt was present in 123 (74.5%) cases. Immediate complications were device embolisation in five (3%) cases and descending aortic obstruction in one case. The overall success rate was 98.2%. Follow-up in 145 (86.3%) cases for 37.1 +/- 24 months (median 34.1) showed further decrease of the PASP to 30.1 +/- 7.7 mm Hg (p<0.0001). CONCLUSIONS: Percutaneous treatment of hypertensive PDA is safe and effective. ADO works well for most cases, but sometimes other devices (MVSDO or ASO) have to be used. When cases are selected adequately, pulmonary pressures decrease immediately and continue to fall with time. PMID- 20357391 TI - Missing data in repeated measures study. PMID- 20357393 TI - The Doppler flow wire in acute myocardial infarction. AB - Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15 70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI. PMID- 20357394 TI - Peripheral arterial disease. Current evidence for carotid endarterectomy and carotid artery stenting. PMID- 20357395 TI - Brugada-pattern ECG and cardiac arrest in cocaine toxicity: reading between the white lines. PMID- 20357396 TI - Recognising bicuspid aortic stenosis in patients referred for transcatheter aortic valve implantation: routine screening with three-dimensional transoesophageal echocardiography. PMID- 20357397 TI - Letter to the editor. The treatment of tibial stress fractures in elite dancers. PMID- 20357398 TI - Letter to the editor. The effects of timing of pediatric knee ligament surgery on short-term academic performance in school-aged athletes. PMID- 20357400 TI - Fair trade? PMID- 20357401 TI - Effect of age on functional and structural outcome after rotator cuff repair. AB - BACKGROUND: There are numerous reports on the outcome of rotator cuff repair according to age. However, the results are conflicting and driven by univariate analysis, which is not free of confounding factors. HYPOTHESIS: Age does not affect the anatomical and functional outcomes of rotator cuff repair. STUDY DESIGN: Case series; Level of evidence, 4. MATERIALS AND METHODS: Eighty-one men and 96 women underwent rotator cuff repair at one institution and received computed tomography arthrography and functional evaluations at least 1 year after surgery. Various structural and clinical features according to age were evaluated. The correlation was assessed between age and outcomes, with adjustment for the preoperative score. RESULTS: Patient mean age was 60.0 +/- 8.7 years. The mean ages were higher in women, nonsmokers, and those with positive paradoxical abduction, lower level of sports activity, the presence of biceps injury, higher fatty degeneration in cuff muscles, inferior isokinetic muscle performance, bigger tear size, more retraction of tear, and symptomatic acromioclavicular arthritis. For the integrity of the repair, the mean age was higher in the retear group (31.1%) than in the intact group (68.9%)-that is, 63.7 +/- 7.5 and 58.4 +/- 8.7 years, respectively (P <.001). Only the Constant score exhibited a positive correlation with age after adjustment (P = .009). Univariate regression analysis revealed that a 0.313-point increment of Constant score could be expected for each year of age. CONCLUSION: On univariate analysis, older age was related with poor postoperative integrity and better functional improvement in Constant score. Multivariate regression revealed that age was not an independent determinant for anatomical or functional outcome whereas the tear retraction and fatty degeneration of the infraspinatus were independent factors for the integrity of repair and the presence of the paradoxical abduction and abduction torque of the unaffected shoulder for the Constant score. PMID- 20357402 TI - Biomechanical analysis of an ovine rotator cuff repair via porous patch augmentation in a chronic rupture model. AB - BACKGROUND: Rotator cuff repair is a commonly performed procedure, but many of these repairs fail in the postoperative term. Despite advances in surgical methods to optimize the repair, failure rates still persist clinically, thereby suggesting the need for novel mechanical or biological augmentation strategies. Nonresorbable implants provide an appealing approach because patch materials may confer acute mechanical stability and act as a conductive scaffold for tissue ingrowth at the site of the tendon insertion. HYPOTHESIS: The polyurethane scaffold mesh will confer greater biomechanical function relative to a nonaugmented repair after 12 weeks in vivo using a chronic ovine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: After development of the chronic rupture model, the tensile failure properties of the nonresorbable mesh-augmented repair (n, 9) were compared with those of a surgical control in an ovine model (n, 8). RESULTS: Rotator cuff repair with the scaffold mesh in the chronic model resulted in a significant 74.2% increase in force at failure relative to the nonaugmented surgical control (P = .021). Apparent increases in stiffness (55.4%) and global displacement at failure (21.4%) in the mesh-augmented group relative to nonaugmented controls were not significant (P = .126 and P = .123, respectively). At the study endpoint, the augmented shoulders recovered 37.8% and 40.7% of the force at failure and stiffness, respectively, of intact, nonoperated controls. CONCLUSION: Using the previously described chronic rupture model, this study demonstrated that repair of a chronic tendon tear with the polyurethane scaffold mesh provides greater mechanical strength in the critical healing period than that of traditional suture anchor repair. CLINICAL RELEVANCE: This device could be used to enhance the surgical repair of the rotator cuff and consequently improve long-term clinical outcome. PMID- 20357403 TI - Which method of rotator cuff repair leads to the highest rate of structural healing? A systematic review. AB - BACKGROUND: The purpose of rotator cuff repair is to diminish pain and restore function, and this most predictably occurs when the tendon is demonstrated to heal. Recent improvements in repair methods have led to improved biomechanical performance, but this has not yet been demonstrated to result in higher healing rates. The purpose of our study was to determine whether different repair methods resulted in different rates of recurrent tearing after surgery. HYPOTHESES: We hypothesized that (1) the rotator cuff repair method will not affect retear rate, and (2) the surgical approach will not affect the retear rate for a given repair method. STUDY DESIGN: Systematic review of the literature. METHODS: The literature was systematically searched to find articles reporting imaging study assessment of structural healing rates after rotator cuff repair, with data stratified according to tear size. Retear rates were compared for transosseous (TO), single-row suture anchor (SA), double-row suture anchor (DA), and suture bridge (SB) repair methods, as well as for open (O), miniopen (MO), and arthroscopic (A) approaches. RESULTS: Retear rates were available for 1252 repairs collected from 23 studies. Retear rates were significantly lower for double-row repairs when compared with TO or SA for all tears greater than 1 cm and ranged from 7% for tears less than 1 cm to 41% for tears greater than 5 cm, in comparison with retear rates for single-row techniques (TO and SA) of 17% to 69% for tears less than 1 cm and greater than 5 cm, respectively. There was no significant difference in retear rates between TO and SA repair methods or between arthroscopic and nonarthroscopic approaches for any tear size. CONCLUSION: Double-row repair methods lead to significantly lower retear rates when compared with single-row methods for tears greater than 1 cm. Surgical approach has no significant effect on retear rate. PMID- 20357407 TI - Enhanced photoluminescence due to lateral ordering of GeSi quantum dots on patterned Si(001) substrates. AB - Multilayer ordered GeSi quantum dots (QDs) with thin Si spacers were obtained via self-assembly on pit-patterned Si(001) substrates. The lateral ordering of GeSi QDs predetermined by the periodic pit pattern results in remarkably improved size uniformity in comparison with random QDs on flat substrates. A much stronger and narrower photoluminescence (PL) peak from ordered QDs were observed than that from random ones, particularly at high excitation power. Such enhanced PL signal was attributed to the high density of states and the uniform distribution of excitons in the ordered and uniform QDs, which can efficiently suppress the Auger effect and the Coulomb screening effect. Moreover, anomalous narrowing of the PL peak from the ordered QDs with the excitation power was observed, which was explained in terms of distributed feedback associated with the periodic stacked GeSi QDs. PMID- 20357408 TI - Swift heavy ion irradiation induced enhancement in the antioxidant activity and biocompatibility of polyaniline nanofibers. AB - Polyaniline (PAni) nanofibers doped with HCl and CSA have been irradiated with 90 MeV O(7+) ions with fluence of 3 x 10(10), 3 x 10(11) and 1 x 10(12) ions cm(-2). TEM micrographs show a decrease in the fiber diameter with increasing irradiation fluence, which has been explained on the basis of the Coulomb explosion model. XRD analysis reveals a decrease in the crystalline domain length and an increase in the strain. The increase in d-spacing for the (100) reflection with increasing irradiation fluence is ascribed to the increase in the tilt angle of the polymer chain, which is also evident from micro-Raman spectra. UV-vis spectra of the PAni nanofibers exhibit blue-shift in the absorption bands attributed to pi-pi* band transitions indicating a reduction in particle size after SHI irradiation; as also observed in TEM micrographs. Micro-Raman spectra also reveal a transition from the benzenoid to quinoid structures in the PAni chain as the fluence is increased. Although the quinoid unit has no hydrogen for DPPH scavenging, the antioxidant activity of PAni nanofibers is found to increase with increasing fluence. This has been attributed to the availability of more reaction sites as a result of fragmentation of the PAni nanofibers which compensates for the benzenoid to quinoid transition after irradiation. The biocompatibility of the PAni nanofibers is also found to increase with increasing irradiation fluence, indicating the possibility of employing swift heavy ion irradiation as an effective technique in order to modify conducting polymer nanostructures for biomedical applications. PMID- 20357410 TI - The fabrication of ordered arrays of exchange biased Ni/FeF2 nanostructures. AB - The fabrication of ordered arrays of exchange biased Ni/FeF(2) nanostructures by focused ion beam lithography is reported. High quality nano-elements, with controlled removal depth and no significant re-deposition, were carved using small ion beam currents (30 pA), moderate dwell times (1 micros) and repeated passages over the same area. Two types of nanostructures were fabricated: square arrays of circular dots with diameters from 125 +/- 8 to 500 +/- 12 nm and periodicities ranging from 200 +/- 8 to 1000 +/- 12 nm, and square arrays of square antidots (207 +/- 8 nm in edge length) with periodicities ranging from 300 +/- 8 to 1200 +/- 12 nm. The arrays were characterized using scanning ion and electron microscopy, and atomic force microscopy. The effect of the patterning on the exchange bias field (i.e., the shift in the hysteresis loop of ferromagnetic Ni due to proximity to antiferromagnetic FeF(2)) was studied using magneto transport measurements. These high quality nanostructures offer a unique method to address some of the open questions regarding the microscopic origin of exchange bias. This is not only of major relevance in the fabrication and miniaturization of magnetic devices but it is also one of the important proximity phenomena in nanoscience and materials science. PMID- 20357409 TI - Monte Carlo simulation of focused helium ion beam induced deposition. AB - The details of a Monte Carlo helium ion beam induced deposition simulation are introduced and initial results for reaction rate and mass transport limited growth regimes are presented. Reaction rate limited growth leads to fast vertical growth from incident primary ions and minimal lateral broadening, whereas mass transport limited growth has lower vertical growth velocity and exhibits broadening due to scattered ions and secondary electrons. The results are compared to recent experiments and previous electron beam induced deposition simulations. PMID- 20357411 TI - Low-cost and large-scale synthesis of graphene nanosheets by arc discharge in air. AB - Large scale production of graphene nanosheets was achieved by arc evaporation of a graphite rod in air. The graphene nanosheets are approximately 100-200 nm wide and the number of layers is mainly in the range of 2-10. Several tens of grams of product were obtained per day. The yield of graphene nanosheets was found to be dependent on the pressure of the air, i.e. high pressure facilitates the formation of graphene nanosheets, but low pressure favors the growth of other carbon nanostructures including carbon nanohorns and nanospheres. Based on this result, a pressure-induced mechanism of formation of graphene nanosheets is proposed. The impurities in the products could be eliminated by oxidation in air. PMID- 20357412 TI - Highly UV luminescent ZnO microtetrapod-on-nanowire hybrids. AB - The author reports the first all-ZnO microtetrapod-on-nanowire hybrids using the cost-effective Au nanoseed assisted open static atmospheric pressure vapor transport method. The unconventional ZnO flower analogue hybrid structure consists of center-tapered ZnO microtetrapods (typically 1-2 microm in dimension) on ZnO 'backbone' nanowires (typically 20 nm in diameter). Three new Raman peaks, centered at 225, 275, 561 cm( - 1), never seen before in ZnO nanocrystals, were first observed in the ZnO hybrids. The hybrids exhibit excellent luminescent properties with a single ultraviolet emission band centered at about 377 nm with an ultra-narrow full width at half maximum of approximately 4 nm, which makes it a promising candidate for optoelectronic applications. A preliminary self assembled synergic growth mechanism is proposed to understand the formation of the structurally stable morphology where the vapor-liquid-solid and vapor-solid mode work together. Our results could open up possibilities for making ZnO nanocrystals to a new level of more complex nanoarchitectures. PMID- 20357413 TI - Long-term hepatotoxicity of polyethylene-glycol functionalized multi-walled carbon nanotubes in mice. AB - The toxicity of polyethylene-glycol functionalized (PEGylated) multi-walled carbon nanotubes (MWCNTs) and non-PEGylated MWCNTs in vivo was evaluated and compared. Mice were exposed to MWCNTs by intravenous injection. The activity level of glutathione, superoxide dismutase and gene expression in liver, as well as some biochemical parameters and the tumor necrosis factor alpha level in blood were measured over 2 months. The pathological and electron micrographic observations of liver evidently indicate that the damage caused by non-PEGylated MWCNTs is slightly more severe than that of PEGylated MWCNTs, which means that PEGylation can partly, but not substantially, improve the in vivo biocompatibility of MWCNTs. PMID- 20357414 TI - Inorganic salt-induced phase control and optical characterization of cadmium sulfide nanoparticles. AB - Phase-controlled synthesis of CdS nanoparticles from zinc-blende to wurtzite has been successfully realized by an inorganic salt-induced process with no use of surfactants or other ligands in an ultrasound-assisted microwave synthesis system. Pure zinc-blende CdS nanoparticles were produced without adding NaCl, while mixed zinc-blende and wurtzite nanoparticles were obtained by adding NaCl/Cd(2+) molar ratios below 1, and pure wurtzite nanoparticles were produced at a molar ratio of 1. The energy bandgap (E(g)) of the CdS nanoparticles calculated from optical absorption spectra increases as the phase transformation from zinc-blende to wurtzite occurs. Additionally, the CdS nanoparticles showed a 489 nm band-edge emission without adding NaCl, and a 501 nm emission when the molar ratios of NaCl to Cd(2+) are 0.25, 0.5 and 1. It was found that the phase transformation originates from the effect of the halide ion Cl(-). We also found that some other halide ions such as Br(-) and I(-) can induce the phase transformation. It is shown that the phase, size and optical properties of the anisotropic nanoparticles can be well tuned by varying the concentration of the halide ions. PMID- 20357415 TI - Long-term stability and minimal detectable change of the cervical flexion rotation test. AB - STUDY DESIGN: Reliability of clinical measurements over time. OBJECTIVES: To determine the long-term stability and minimal detectable change (MDC) of the flexion-rotation test (FRT) measurements over days in subjects with cervicogenic headache (CGH). BACKGROUND: The FRT is used by physical therapists to assist in identifying upper cervical movement impairment, as well as to gauge treatment effectiveness. Test-retest reliability for the FRT has been reported, but the stability of range-of-motion measures taken during the FRT over time and the MDC have not been investigated. METHODS: Fifteen subjects with CGH were evaluated on headache-free days using the FRT by a blinded examiner at baseline, 2, 4, and 14 days later. An additional 10 asymptomatic subjects were included for blinding purposes. On each occasion, the examiner measured range of motion and determined whether the FRT was positive or negative. RESULTS: For subjects with CGH, there was no significant change in FRT range of motion over days (P>.05). Intraclass correlation coefficients for intratester reliability were 0.95 (95% CI: 0.90 to 0.98) and 0.97 (95% CI: 0.94 to 0.99) for right and left rotation, respectively. MDC90 was 4.7 degrees for right rotation and 7 degrees for left rotation. Examiner interpretation of the FRT was consistent over time, with kappa = 0.92. CONCLUSIONS: This study provides evidence that FRT measurements are stable over time, and the MDC90 indicates that a change in FRT range of motion of at least 7 degrees is required to be confident that a change has occurred due to an intervention rather than measurement error. PMID- 20357416 TI - Rehabilitation following lumbosacral percutaneous nucleoplasty: a case report. AB - STUDY DESIGN: Case report. BACKGROUND: Lumbar spine nucleoplasty is a new surgical option for patients with disc pathology. There are no reports in the literature describing the role of physical therapy in postoperative lumbar nucleoplasty management. The purpose of this case is to describe the postoperative physical therapy management of a patient who underwent this procedure. CASE DESCRIPTION: A 50-year-old male, 7 weeks following a L5/S1 lumbar nucleus replacement, completed 6 weeks of rehabilitation. The focus of the treatment was controlled reloading of the spine through a spinal stabilization progression in weight-bearing and non-weight-bearing activities. In addition, education, spinal manual therapy techniques, and a home exercise program were also incorporated. OUTCOMES: The patient's Oswestry Disability Index decreased from 56% to 4% over 6 weeks of treatment. When contacted at 6, 12, 18, and 24 months posttherapy, his Oswestry Disability Index was 2%, 2%, 0%, and 0%, respectively, and he had returned to all previous activities without recurrence of symptoms. DISCUSSION: This case report outlines the clinical decision-making process during the postoperative management of an individual who had undergone a single-level lumbar nucleoplasty. A postoperative regimen of education, segmental spinal stabilization, and a home exercise program might have contributed to the observed improvement in pain and disability levels in this patient. The role of these postoperative interventions warrants further research. LEVEL OF EVIDENCE: Therapy, level 4. PMID- 20357417 TI - Reducing impact loading during running with the use of real-time visual feedback. AB - STUDY DESIGN: Single-subject with repeated measures. OBJECTIVES: To determine if runners can use real-time visual feedback from an accelerometer to achieve immediate reductions in tibial acceleration and vertical-force loading rates. BACKGROUND: Stress fractures are a common injury among runners. Previous studies suggest that runners with higher than normal tibial acceleration and vertical force loading rates are at increased risk for tibial stress fractures. If these runners can be trained to reduce the loading on their lower extremities, it may reduce their risk of stress fractures. METHODS: Five subjects participated in this study. All subjects ran on a treadmill, instrumented with force transducers, during a single 30-minute session that was divided into warm-up, feedback, no feedback, and cool-down periods. During running, the subjects also wore an accelerometer taped to their distal right tibia. Peak positive acceleration of the tibia, vertical force impact peak, and average and instantaneous vertical force loading rates were assessed at the end of the warm-up, feedback, and no feedback periods. RESULTS: Single-subject analysis revealed that 4 of the 5 subjects had significant reductions in their peak positive acceleration at the end of the no-feedback period compared to the warm-up. In addition, all of the subjects had significant decreases in impact peak and vertical ground reaction force loading rates at the end of the no-feedback period. CONCLUSION: In a single session of training with real-time visual feedback, it appears that most runners can reduce the types of lower extremity loading associated with stress fractures. This may lead to training programs that reduce the risk of stress fractures for runners. PMID- 20357419 TI - JOSPT honors authors for research and clinical inquiry papers at CSM 2010. PMID- 20357418 TI - A psychometric investigation of fear-avoidance model measures in patients with chronic low back pain. AB - STUDY DESIGN: Validity and test-retest reliability of questionnaires related to the fear-avoidance model (FAM). OBJECTIVE: To investigate test-retest reliability, construct redundancy, and criterion validity for 4 commonly used FAM measures. BACKGROUND: Few studies have reported psychometric properties for more than 2 FAM measures within the same cohort, making it difficult to determine which specific measures should be implemented in outpatient physical therapy settings. METHODS: Fifty-three consecutive patients (mean age, 44.3 + or - 18.5 years) with chronic low back pain participated in this study. Data were collected with validated measures for FAM constructs, including the Fear-Avoidance Beliefs Questionnaire (FABQ), Fear of Pain Questionnaire (FPQ), Tampa Scale for Kinesiophobia, and Pain Catastrophizing Scale. Validated measures were used to investigate criterion validity of the FAM measures, including the Patient Health Questionnaire for depression, the numerical rating scale for pain intensity, the Physical Impairment Scale for physical impairment, and the Oswestry Disability Questionnaire for self-report of disability. Test-retest reliability of the FAM measures was determined with intraclass correlation coefficients (ICC2,1) for total questionnaire scores at baseline and 48 hours later. Construct redundancy was determined with Pearson correlation coefficients for FAM measures. Criterion validity was assessed by 4 separate multiple regression models that included age, sex, and employment status as covariates. Depression, pain intensity, physical impairment, and disability were the dependent variables for these analyses. RESULTS: Test-retest ICC coefficients ranged from 0.90 to 0.96 for all FAM questionnaires. The FAM measures were significantly correlated with each other, with the only exception being that the FPQ was not correlated with the FABQ work scale. In the multiple regression models, the Pain Catastrophizing Scale contributed additional variance to depression. The FABQ physical activity scale contributed additional variance to pain intensity and disability. The FABQ work scale contributed additional variance to physical impairment and disability. No other FAM measures contributed to these regression models. CONCLUSION: These data suggest that 4 commonly used FAM measures have similar test-retest reliability, with varying amounts of construct redundancy. The criterion validity analyses suggest that measurement of fear-avoidance constructs for patients seeking outpatient physical therapy with chronic low back pain should include the Pain Catastrophizing Scale and the FABQ. PMID- 20357421 TI - Osteochondral lesion of the talus. PMID- 20357423 TI - Mirror syndrome: a systematic review of fetal associated conditions, maternal presentation and perinatal outcome. AB - INTRODUCTION: Mirror syndrome, also referred to as Ballantyne's syndrome, is normally defined as the development of maternal edema in association with fetal hydrops. The incidence of mirror syndrome is low and few cases have been published. We describe a case report in association with fetal Ebstein anomaly and provide a systematic review on the fetal associated conditions, maternal presentation and perinatal outcome reported for mirror syndrome. DATA SOURCES: A PubMed database search was done until December 2008 (English, French or German) without any restriction of publication date or journal, using the following key words: Ballantyne syndrome, Mirror syndrome, Triple edema, Pseudotoxemia, Maternal hydrops syndrome, Pregnancy toxemia, Acute second trimester gestosis, and Early onset preeclampsia. Reported cases were considered eligible when fetal associated conditions, maternal symptoms and fetal outcome were clearly described. RESULTS: Among 151 publications a total of 56 reported cases satisfying all inclusion criteria were identified. Mirror syndrome was associated with rhesus isoimmunization (29%), twin-twin transfusion syndrome (18%), viral infection (16%) and fetal malformations, fetal or placental tumors (37.5%). Gestational age at diagnosis ranged from 22.5 to 27.8 weeks of gestation. Maternal key signs were edema (80-100%), hypertension (57-78%) and proteinuria (20-56%). The overall rate of intrauterine death was 56%. Severe maternal complications including pulmonary edema occurred in 21.4%. Maternal symptoms disappeared 4.8-13.5 days after delivery. DISCUSSION: Mirror syndrome is associated with a substantial increase in fetal mortality and maternal morbidity. PMID- 20357424 TI - Pleomorphic adenoma of the trachea. PMID- 20357420 TI - Knee stability and movement coordination impairments: knee ligament sprain. PMID- 20357425 TI - Thoracoscopic findings and pharmacokinetics of inhaled fluorescein in a pig model. AB - BACKGROUND: Fluorescein-enhanced autofluorescence thoracoscopy (FEAT) reveals regions of abnormal fluorescence in patients with primary spontaneous pneumothorax and in normal subjects. Some of these lesions are undetectable by white light thoracoscopy and it has been hypothesized that they represent underlying pleural and/or parenchymal abnormalities. OBJECTIVES: In order to standardize and evaluate this novel technique, we developed an animal model. METHODS: Six pigs underwent thoracoscopy after the inhalation of nebulized sodium fluorescein by either volume-controlled mechanical ventilation or spontaneous ventilation. Pleural cavity and lung surface were inspected by white light thoracoscopy and FEAT during a period of 90 min. Fluorescence intensities were quantified in pleura and in blood. Regions of interest were examined postmortem for a histological assessment of the lesions. RESULTS: FEAT lesions were observed in all animals, with a maximum intensity of the lesions 20-30 min after the onset of fluorescein administration. The plasma concentrations of sodium fluorescein reached a maximum after approximately 20 min. The microscopic findings suggest that fluorescein accumulates in the subpleural space of better ventilated lung areas. CONCLUSIONS: This is the first animal model using FEAT. Valuable information has been gathered but further investigations are required to explain the phenomena observed in humans and pigs. PMID- 20357426 TI - Estimating peak work rate during incremental cycle ergometry from the 6-minute walk distance: differences between reference equations. AB - BACKGROUND: Prescription of an appropriate exercise training intensity is critical to optimise the outcomes of pulmonary rehabilitation; however, prescribing cycle ergometry training is challenging if peak work is unknown. Recently two studies reported regression equations which allow estimation of peak cycle work rate from the 6-minute walk distance (6MWD) in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To compare estimates of peak work and target training work rate (60% peak) obtained from these equations. METHODS: Sixty-four (38 male) subjects, mean +/- SD age 70 +/- 8 years and FEV(1) 49 +/- 18% predicted with COPD performed the 6-minute walk test according to a standardised protocol. Estimates of peak work were obtained using the published equations and agreement was examined using Bland and Altman plots. RESULTS: Mean 6MWD was 376 +/- 86 m compared to 464 +/- 110 m and 501 +/- 83 m in samples used to derive the equations. There was substantial variation in estimates of peak work between equations (range 1-75 Watts difference) with a coefficient of variation of 35%. Differences were greater in men than in women (p < 0.001). The Luxton equation predicted higher peak work than the Hill equation in younger subjects and at work rates over 50 Watts. Estimated training work rate differed by more than 20 Watts in 18 subjects (28%). CONCLUSIONS: This comparison of reference equations for predicting peak cycle work rate from 6MWD indicates substantial variation between methods that differs systematically across the range of work rates. Further research is required to validate the equations and assess their utility for exercise prescription in pulmonary rehabilitation. PMID- 20357427 TI - Blood pressure in the first year of life in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a pilot study. AB - AIMS: Evaluation of blood pressure in the first year of life in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. METHODS: Twenty-four children were included. Retrospective blood pressure values, fludrocortisone dosages, and serum renin, 17-hydroxyprogesterone (17-OHP) and androstenedione levels in the first year of life were evaluated. Blood pressure values were compared to reference values. Correlations between blood pressures and serum renin levels, and the dosage of fludrocortisone were calculated. RESULTS: Mean peak systolic blood pressure values were generally not elevated, most values were around the 50th percentile, except incidentally higher mean peak systolic blood pressure values most below the 95th percentile. No significant correlations between blood pressure and serum renin, androstenedione and 17-OHP levels and fludrocortisone dosage were found. CONCLUSION: In this pilot study in CAH patients, blood pressure values do not seem to be elevated in the first year of life. Further investigations are necessary to evaluate blood pressure in the first year of life in CAH patients in more detail. PMID- 20357428 TI - Disparate companions: tissue engineering meets cancer research. AB - Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit. PMID- 20357429 TI - MicroRNA profiles of drug-resistant myeloma cell lines. PMID- 20357430 TI - C-peptide as a therapeutic tool in diabetic nephropathy. AB - BACKGROUND/AIMS: Insulin is synthesised as a pro-hormone with an interconnecting C-peptide, cleaved during post-translational modification. This review discusses growing evidence which indicates that C-peptide is biologically active, benefiting microvascular complications associated with diabetes. METHODS: To explore the renoprotective role of C-peptide in diabetic nephropathy (DN), we reviewed the literature using PubMed for English language articles that contained key words related to C-peptide, kidney and DN. RESULTS: Numerous studies have demonstrated that C-peptide ameliorates a number of the structural and functional renal disturbances associated with uncontrolled hyperglycaemia in human and animal models of type 1 diabetes mellitus that lead to the development and progression of nephropathy, including abrogation of glomerular hyperfiltration, reduced microalbuminuria, decreased mesangial expansion and increased endothelial nitric oxide synthase levels. The in vitro exposure of kidney proximal tubular cells to physiological concentrations of C-peptide activates extracellular signal regulated kinase, phosphatidylinositol 3-kinase, protein kinase C, elevates intracellular calcium, and stimulates transcription factors NF-kappaB and peroxisome proliferator-activated receptor-gamma. CONCLUSION: Burgeoning studies suggest that C-peptide is more than merely a link between the A and B chains of the proinsulin molecule and represents a future therapeutic tool in reducing complications of DN. PMID- 20357431 TI - Hepatitis E virus infection: a general review with a focus on hemodialysis and kidney transplant patients. AB - BACKGROUND: Hepatitis E virus (HEV) infection is a self-limited viral disease that causes acute hepatitis epidemics in developing countries. The common route of transmission for HEV is supposedly fecal-oral. Serological evidence may be unexpectedly found in hemodialysis (HD) patients and kidney transplant recipients. Although the route of HEV transmission is not usually determined in HD subjects, this virus seems to be transmitted either directly through HD or nosocomially. In this study, we gathered the published information on HEV infection in HD patients and kidney transplant recipients. METHODS: For this review, we collected the relevant articles by searching through Medline and Google Scholar from January 1980 up to September 2009. RESULTS: Some variables including older age, low education, living in rural versus urban areas and the duration of HD seem to be risk factors for HEV infection in HD patients. Compared with non-HD subjects, HEV infection may be specifically associated with poor outcome in HD patients. Specific considerations seem to be required to prevent transmission of HEV to HD patients. CONCLUSION: More extensive investigations are required to determine the disease burden of HEV infection in HD subjects in countries which experience outbreaks of HEV infection. PMID- 20357432 TI - Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth. AB - BACKGROUND/OBJECTIVE: Hypoketotic hypoglycaemia and hypertriglyceridaemia are biochemical hallmarks of glycogen storage disease (GSD) 1. Increased malonyl coenzyme A production which compromises oxidation of long-chain fatty acids via carnitine palmitoyltransferase (CPT) 1 inhibition plays a crucial role in the pathogenesis of these complications. Therapy consists primarily of nutritional support including frequent carbohydrate-rich meals. We studied the effect of a diet enriched in medium-chain triglycerides (MCT) on metabolic control/growth in GSD 1 as medium-chain fatty acids can be oxidised independently of CPT 1. METHODS: An adult female, a 1.6-year-old boy with GSD 1a and a 6.5-year-old girl with GSD 1b treated with a classical GSD diet were enrolled; their 'classical GSD diet' was supplemented with MCT fats. Concentrations of glucose, lactate, ketone bodies triglycerides, uric acid, acylcarnitines in blood and organic acids in urine were determined. RESULTS: No clinical or biochemical side-effects were observed. The MCT diet led to a decrease in uric acid concentrations in all patients. Triglyceride levels were reduced only in the youngest patient, while lactate concentrations did not significantly decrease. The MCT diet allowed for a reduction in carbohydrate and caloric intake required to maintain euglycaemia and led to improvement in growth in the two prepubertal patients. CONCLUSIONS: MCT supplementation had a positive effect on metabolic control and growth in our patients suffering from GSD 1. PMID- 20357433 TI - Early and sustained systemic and renal hemodynamic effects of intravenous radiocontrast. AB - BACKGROUND AND AIMS: To measure the extended renal hemodynamic changes induced by intravenous radiocontrast. METHODS: Cross-ewes were studied in a randomized cross over study. Intravenous saline or radiocontrast were administered, and continuous measurement of cardiac output and renal blood flow (RBF) was performed with flow probes. RESULTS: Radiocontrast induced early but transient increases in cardiac output with vasodilatation, followed by return to baseline values within 2 h. There was an initial decline in RBF (-5.2 +/- 4.5 vs. 2.1 +/- 5.3%; p < 0.0001) and decreased renal vascular conductance (-4.0 +/- 7.2 vs. 3.3 +/- 7.1%, p < 0.0001; vasoconstriction). This renal vasoconstriction resolved within 2 h and was followed by sustained (72 h) renal vasodilatation with higher RBF (270 +/- 13 vs. 236 +/- 11 ml/min; p < 0.0001). CONCLUSIONS: Radiocontrast induces short renal vasoconstriction followed by sustained vasodilatation and increased RBF. Short-term studies are not representative of the overall sustained renal hemodynamic effects of radiocontrast. PMID- 20357434 TI - Vascular calcification and cardiovascular outcome in dialysis patients: the role of gene polymorphisms. AB - Vascular calcification and accelerated atherosclerosis are major causes of death in hemodialysis (HD) patients. Epigenetic mechanisms of gene regulation may be crucial determinants of cellular behavior in uremic conditions, determining an increased risk of cardiovascular morbidity and mortality. The common polymorphisms on different gene promoters have been related to increased coronary artery calcification and associated with cardiovascular outcome in HD population. In this review, we reported the gene polymorphisms of different proteins as negative prognostic risk factors for all-cause mortality in HD patients, independent of traditional risk factors. These data may have important implications for better understanding the pathogenesis of the increased mortality in this population. PMID- 20357435 TI - Sevelamer decreases systemic inflammation in parallel to a reduction in endotoxemia. AB - INTRODUCTION: Uremic toxins play a pivotal role in the development of systemic complications of chronic kidney disease (CKD), which are largely mediated by the activation of the immune system. Triggers of inflammation in CKD are largely unknown and strategies aiming to reduce circulating ligands that could start the inflammatory response are potentially important. In the present study, we investigated the impact of sevelamer hydrochloride treatment in reducing endotoxemia and inflammation in a group of hemodialysis (HD) patients. MATERIAL AND METHODS: HD patients, who were converted from calcium carbonate treatment to sevelamer according to KDOQI guidelines, were included and prospectively followed for 6 months. Systemic inflammation was evaluated by serum ultra-high-sensitivity C-reactive protein (hsCRP) using an automated immunoturbidimetric assay. Endotoxin was measured using Limulus amebocyte lysate chromogenic endpoint assay. All the analyses were performed immediately before conversion and after 6 months of treatment. RESULTS: After the exclusion of patients discontinuing the treatment, 20 patients (mean dialysis time 12 +/- 4 months on HD, age 52 +/- 2 years, 38% males, 11% diabetics) were included in the analysis. No significant changes were observed in Ca, P and PTH levels, while a reduction in cholesterol levels was seen. Plasma concentration of hsCRP and endotoxin significantly decreased after 6 months of conversion to sevelamer compared with baseline. CONCLUSION: We conclude that sevelamer treatment leads to a decrease in hsCRP levels, which was accompanied by a parallel decrease in endotoxemia, suggesting that endotoxemia may contribute to the systemic inflammation in HD patients, which was partially reduced by the use of sevelamer. PMID- 20357436 TI - Sugar and NICE - aggressive hyperglycaemic control in ischaemic stroke and what can we learn from non-neurological intensive glucose control trials in the critically ill? PMID- 20357437 TI - Navigating the gray zones of stroke management for a graying population. PMID- 20357438 TI - Association of a genetic variant in the ALOX5AP with higher risk of ischemic stroke: a case-control, meta-analysis and functional study. AB - BACKGROUND: Variants in the 5-lipoxygenase-activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) genes have first been associated with ischemic stroke (IS) through whole-genome linkage screens. However, association studies obtained conflicting results. We aimed to investigate the contribution of selected single nucleotide polymorphisms (SNPs) in these genes for the first time in a large Iberian population. METHODS: A case-control design was used to analyze one SNP in ALOX5AP and five SNPs in PDE4D in a total of 1,092 IS patients and 781 healthy controls of two different subsets from Spain and Portugal. The analysis was adjusted for confounding variables and the results were integrated in a meta analysis of all case-control studies. In addition, ALOX5AP gene expression levels were determined in controls and IS cases. RESULTS: A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in ALOX5AP was a risk factor for IS after Bonferroni correction [OR = 1.22 (1.06-1.40); p = 0.006]. A second meta-analysis of white populations confirmed these results [OR = 1.18 (1.07 1.31); p = 0.001]. ALOX5AP gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of ALOX5AP (p = 0.001) and mRNA levels were higher in IS cases (2.8 +/- 2.4%) than in controls (1.4 +/- 1.3%; p = 0.003). No association of the variants in PDE4D with IS was observed in our study. CONCLUSIONS: The ALOX5AP SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with ALOX5AP expression levels. The role of this gene in stroke merits further investigation. PMID- 20357439 TI - Severe pulmonary toxicity associated with fludarabine and possible contribution of rituximab. AB - Fludarabine is a nucleoside analogue used in the treatment of low-grade lymphoproliferative disorders and in conditioning regimens of non-myeloablative allogeneic stem cell transplantation. This is a relatively safe drug for clinical use but may cause side effects, some of which may be life-threatening. Here a case of severe pulmonary toxicity associated with fludarabine and a possible contribution of rituximab is presented and the literature reviewed. PMID- 20357440 TI - Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. AB - BACKGROUND: The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase II trial was conducted to determine the efficacy and tolerability of capecitabine and oxaliplatin (XELOX) given every 3 weeks in combination in patients with AGC. METHODS: Patients with previously untreated AGC received intravenous oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks. Treatment was continued for 8 cycles or until disease progression or intolerable toxicity. RESULTS: Fifty patients were enrolled. In total, 210 cycles of XELOX were delivered. The OVERALL response rate was 42% (95% CI 28.6-56.7), with 2 complete and 19 partial responses. At 15.2 months of median follow-up, median time to progression and overall survival were 5.8 (95% CI 3.4-8.2) and 11.1 (95% CI 5.6-16.5) months, respectively. The most common hematological adverse event was neutropenia (56% of patients); grade 3-4 neutropenia was observed in 6 patients, with neutropenic fever in only 2 patients. The most common non-hematological toxicities were vomiting (34%), hand-foot syndrome (26%), diarrhea (24%) and neurosensory toxicity (22%). There were no treatment-related deaths. CONCLUSIONS: XELOX is active for the first-line treatment of AGC with a manageable tolerability profile. PMID- 20357441 TI - Molecular mechanism of cell apoptosis by paclitaxel and pirarubicin in a human osteosarcoma cell line. AB - BACKGROUND: Paclitaxel and pirarubicin exhibit cytotoxic and antitumor activities. However, little is known about the apoptosis-inducing effects of paclitaxel and pirarubicin on human osteosarcoma MG-63 cells. METHODS: The effects of paclitaxel and pirarubicin on cell cycle arrest and apoptosis were studied in MG-63 cells using flow cytometry. PCNA, Bcl-2, Bax, cyclin D1 and cyclin E expression was assessed by Western blotting. RESULTS: Paclitaxel and pirarubicin caused G2/M and G0/G1 cell cycle arrest in MG-63 cells, respectively. Apoptosis of MG-63 cells mediated by paclitaxel was dependent on treatment duration. Interestingly, in cells treated with pirarubicin, apoptosis was related to treatment duration at concentrations of 10(2)-10(3) nM, whereas the effect of treatment duration was less marked at concentrations >10(4)-10(5) nM. Furthermore, paclitaxel and pirarubicin suppressed the expression of PCNA, cyclin D1, cyclin E and Bcl-2, and increased Bax expression. CONCLUSION: These results suggest that the G2/M or G0/G1 cell cycle arrest and apoptosis induced by paclitaxel and pirarubicin are Bcl-2/Bax dependent, suggesting favorable effects of combination therapy with paclitaxel and pirarubicin in the treatment of osteosarcoma. PMID- 20357442 TI - Effects of carboxymethyl cellulose-based saliva substitutes with varying degrees of saturation with respect to calcium phosphates on artificial enamel lesions. AB - The aim of the present study was to evaluate the effects of experimental saliva substitutes based on carboxymethyl cellulose (CMC) differing in degrees of saturation with respect to calcium phosphates on the mineral loss of enamel in vitro. Demineralized bovine specimens (subsurface lesions) were exposed to one of six experimental CMC-based solutions with theoretical degrees of saturation with respect to octacalcium phosphate (S(OCP)) of S0, S0.5, S1, S2, S4, and S8 for 10 weeks. A previously studied saliva substitute (Glandosane) and two aqueous solutions (C0 and C1) served as controls. Mineral losses and lesion depths before and after storage were evaluated from microradiographs. Free and bound calcium as well as phosphate and fluoride concentrations were determined. According to these measurements, S(OCP) of S2, S4, and S8 was 0.3, 1.1, and 3.4, respectively. Storage in Glandosane and both negative controls resulted in significant demineralization (p < 0.05). Only S2 significantly remineralized the specimens (p < 0.05). All other solutions showed neutral effects. No significant differences in mineralization between S0 and C0 as well as between S1 and C1 could be observed (p > 0.05). It can be concluded that a CMC-based solution actually unsaturated with respect to octacalcium phosphate (S2) shows most pronounced remineralization capability under the conditions chosen. This might be explained by a more favorable balance between calcium bound to CMC in an adsorbed layer at the enamel-liquid interface and heterogeneous nucleation of calcium phosphates within a solution compared to solutions either supersaturated or having lower levels of saturation. PMID- 20357444 TI - Management of benign liver tumors. PMID- 20357443 TI - Effect of different fluoride concentrations of experimental dentifrices on enamel erosion and abrasion. AB - It has been suggested that fluoride products are able to reduce erosive tooth wear. Thus, the purpose of this in vitro study was to evaluate the effect of dentifrices with different fluoride concentrations as well as of a low fluoridated dentifrice supplemented with trimetaphosphate (TMP) on enamel erosion and abrasion. One hundred twenty bovine enamel blocks were assigned to the following experimental dentifrices: placebo, 1,100 microg F/g, 500 microg F/g plus 3% TMP and 5,000 microg F/g. The groups of enamel blocks were additionally subdivided into conditions of erosion (ERO) and of erosion plus abrasion (ERO + ABR). For 7 days, the blocks were subjected to erosive challenges (immersion in Sprite 4 times a day for 5 min each time) followed by a remineralizing period (immersion in artificial saliva between erosive challenges for 2 h). After each erosive challenge, the blocks were exposed to slurries of the dentifrices (10 ml/sample for 15 s). Sixty of the blocks were additionally abraded by brushing using an electric toothbrush (15 s). The alterations of the enamel were quantified using the Knoop hardness test and profilometry (measurements in micrometers). The data were analyzed using a 2-way ANOVA test followed by a Bonferroni correction (p < 0.05). In in vitro conditions, the 5,000 microg F/g and 500 microg F/g plus 3% TMP dentifrices had a greater protective effect when compared with the 1,100 microg F/g dentifrice, under both ERO and ERO + ABR conditions. The results suggest that dentifrices alone are not capable of completely inhibiting tooth wear. PMID- 20357445 TI - Giant haemangioma of the liver: observation or resection? AB - BACKGROUND: Haemangiomata are the most frequent benign solid liver lesion. The management of giant (> or =5 cm) haemangiomata of the liver remains controversial. METHODS: A search of relevant peer-reviewed literature was conducted using PubMed and original articles were reviewed. RESULTS AND CONCLUSIONS: The vast majority of giant haemangiomata remain asymptomatic and have a benign and uncomplicated natural history. Decisions regarding the optimal management of giant haemangiomata depend on a high level of confidence in diagnostic imaging. Diagnostic biopsy to differentiate giant haemangiomata from malignant lesions should be discouraged. Despite limitations and alternative modalities, surgery remains the only consistently effective curative treatment for giant haemangiomata. Surgery is not generally justified to prevent complications in asymptomatic patients. Principal indications for the surgical management of giant haemangiomata include established complications, incapacitating symptoms and uncertainty of diagnosis. Patients should only be selected for surgery based on a careful assessment of risks and benefits of intervention. PMID- 20357446 TI - Management of congenital bile duct cysts. AB - Bile duct cysts (BDC) are rare congenital anomalies of the biliary tree that are characterized by cystic dilatation of the extrahepatic and/or intrahepatic bile ducts. Presence of an anomalous bilio-pancreatic junction allowing pancreatic juice to reflux into the biliary tree is the most widely aetiopathogenic concept currently accepted. BDC are associated with biliary stasis and lithiasis, and the whole biliary epithelium is considered at risk of malignant transformation. Magnetic resonance cholangio-pancreatography is currently the most accurate preoperative imaging study to assess cyst anatomy and classify the disease according to the standard Todani classification. Complete cyst excision with cholecystectomy followed by biliary reconstruction using a Roux-en-Y hepatico jejunostomy is the treatment of choice for the extrahepatic component of the disease (type I and IV BDC), but cystic involvement up to the roof of the main biliary convergence represents a real surgical challenge to perform complete resection. The optimal treatment of intrahepatic bile duct dilatations remains controversial, especially for type IV-A BDC. In type V BDC (Caroli's disease), extent of the liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver (congenital hepatic fibrosis) and kidney disease. Late postoperative cholangitis secondary to intrahepatic strictures and lithiasis, as well as the risk of metachronous cholangiocarcinoma that can occur throughout the whole biliary tree even after complete cyst excision, represent serious complications justifying careful long-term follow-up. PMID- 20357447 TI - Mucinous cystadenomas in liver: management and origin. AB - BACKGROUND: Mucinous cystadenomas of the liver are rare cystic neoplasms. The aim of this study was to assess management of a consecutive series of patients who underwent laparotomy for a suspected cystadenoma or cystadenocarcinoma. Secondly, the origin of ovarian stroma (OS) in mucinous liver cystadenomas was examined during early embryonic development. PATIENTS AND METHODS: Patients diagnosed with mucinous liver cystadenomas or cystadenocarcinoma between 1994 and 2009 were included. Pathology specimens of patients who had undergone resection were reviewed for OS. Furthermore, in human embryos, morphology of the peritoneal epithelium and the position of the gonads in relation to the embryonic liver, pancreas and spleen were examined. RESULTS: 15 surgically treated patients (13 female, 2 male) with hepatic tumors were eventually diagnosed with mucinous liver cystadenomas (12) or cystadenocarcinomas (3). OS was present in all female patients with mucinous cystadenoma or cystadenocarcinoma. The 2 male patients were rediagnosed as intraductal papillary mucinous neoplasm (IPMN) or cystadenocarcinoma with features of IPMN. In human embryos, preceding their 'descent', the gonads are situated directly under the diaphragm, dorsal to the liver, the tail of the pancreas and the spleen, but separated from these organs by the peritoneal cavity. In contrast to the peritoneal epithelium elsewhere, the cells covering the gonads show an activated morphology. CONCLUSION: For the diagnosis of mucinous liver cystadenoma, the presence of OS is prerequisite. This may be explained by the common origin of cystadenoma and OS in epithelial cells that cover the embryonic gonads in early fetal life. PMID- 20357448 TI - Focal nodular hyperplasia and hepatic adenoma: epidemiology and pathology. AB - Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) represent the most frequent non-vascular benign liver tumors. They are often asymptomatic. The widespread use of high-resolution imaging modalities leads to an increase of incidental detection of FNH and HA. Physicians are thus increasingly confronted with these formerly rarely recognized conditions, stressing the need for concise but adequate information on the optimal clinical strategies for these patients. FNH is the most common non-vascular benign tumor of the liver. It probably arises as a polyclonal, hyperplastic response to a locally disturbed blood flow. It is typically found in asymptomatic women. Histologically, FNH can be described as a focal form of cirrhosis. Complications of FNH are extremely rare and surgical resection is generally not advised. HA is a rare monoclonal, but benign liver tumor primarily found in young females using estrogen-containing contraceptives. Although its exact etiology is unknown, a direct link between sex steroid exposure and the uncontrolled hepatocellular growth is suspected. Complications of HA are spontaneous bleeding and malignant transformation. Withdrawal of estrogen treatment and excision of large tumors (>5 cm) are established therapeutic strategies. In conclusion, although FNH and HA are reasonably well described clinical and histopathological entities, their epidemiology and pathophysiology need to be further unraveled. PMID- 20357449 TI - Malignant transformation of liver adenoma: an analysis of the literature. AB - As adenoma in other locations, hepatic adenoma (HA) may transform into hepatocellular carcinoma (HCC) and hepatocyte dysplasia is most probably the intermediate step between both conditions. Malignant HA may appear as microscopic or macroscopic areas of HCC within the HA. These areas are typically well differentiated and without vascular extension or satellite nodules. AFP measurements are not reliable as they are usually normal. The risk of malignant transformation of HA cannot be reliably quantified yet. Several series are concordant to show that approximately 5% of patients whose HA have been resected had pathological evidence of HCC within their HA. This figure however does not take into account fully transformed HA where evidence of the preexisting benign lesion might have disappeared. The risk of malignant transformation is correlated with the diameter of the HA and it is very unusual when it is <5 cm and the same holds true for patients with multiple HA. These results suggest that small HA could be safely observed as they are also at low risk of bleeding. These conclusions might not apply to male patients who are at lower risk of HA, except in specific conditions, but appear to be at a much higher risk of malignant changes. PMID- 20357450 TI - Subtype classification of hepatocellular adenoma. AB - Hepatocellular adenomas (HCA) are rare benign tumours occurring mainly in women under oral contraceptives. HCA bleed frequently and transform rarely into hepatocellular carcinoma. Identification of genes recurrently mutated in HCA and good genotype/phenotype correlations provided the basis of a pathomolecular classification of different HCA subgroups, characterized using immunohistochemical markers. HNF1A-mutated HCA: Biallelic-inactivating mutations of HNF1A gene are identified in 35-40% of HCA. HNF1alpha-inactivated HCA display characteristic pathological features, including marked steatosis. The expression of FABP1 (which is a HNF1A target gene) is downregulated and the absence of L FABP expression diagnosed this subgroup. beta-Catenin-mutated HCA: beta-catenin mutations leading to activation of the Wnt/beta-catenin pathway represented 10 15% of HCA. They are characterized by overexpression of glutamine synthetase and aberrant nuclear beta-catenin staining. These beta-catenin-activated HCA are at greater risk of malignant transformation; they are difficult to differentiate from well-differentiated HCC. Inflammatory HCA (50%): These are defined by the presence of inflammatory infiltrates, sinusoidal dilatation and thick-walled arteries. Small in-frame deletions that target the binding site of gp130 for IL-6 have been reported in 60% of inflammatory HCA. There is an overexpression of the inflammatory proteins serum amyloid A and C-reactive protein in tumour hepatocytes both at mRNA and protein levels. Inflammatory HCA occurred more frequently in patients with high body mass index; they can be also mutated for beta-catenin and therefore are probably at risk of HCC. Unclassified HCA: Less than 10% of HCA do not express any of the above-mentioned phenotypic markers. Taking into account noticeable differences between the HCA subgroups, in terms of clinical and prognostic features, phenotyping may become an important tool for HCA management strategy. PMID- 20357451 TI - Imaging modalities for focal nodular hyperplasia and hepatocellular adenoma. AB - BACKGROUND/AIMS: There are several imaging modalities available for the detection of focal liver lesions. Differentiation between focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is important because of the consequences for management. However, differentiation based on imaging alone still shows limitations. METHODS: We reviewed the literature for typical features of FNH and HCA on radiologic and nuclear imaging with emphasis on differentiation of both lesions. RESULTS: Seven articles describe the performance of an imaging modality for the differentiation between FNH and HCA. Limitations of these studies are the small sample size and/or the lack of comparison with the 'gold standard', i.e. histological diagnosis. No studies are available that compare the accuracy of several imaging modalities in the differentiation of FNH and HCA. Conventional ultrasound (US) is not useful in the differentiation because of the non-specific features. On contrast-enhanced US, the arterial filling direction of FNH is centrifugal and centripetal in case of HCA. The parenchymal enhancement of FNH is sustained in the portal venous and delayed phases, but shows rapid washout in case of HCA. Multiphase CT scan can differentiate FNH from HCA when there is a central scar. FNH may have a slightly higher relative enhancement in the arterial phase. On MRI with hepatocyte-specific contrast agents, HCA does not show contrast uptake in the hepatobiliary phase in contrast to FNH. CONCLUSION: We conclude that there is limited evidence of the diagnostic performance of currently used imaging modalities for the differentiation of FNH and HCA. We therefore propose a prospective study (DiFA trial) to determine the accuracy of several radiologic and nuclear imaging studies in differentiating FNH and HCA. PMID- 20357452 TI - Management of ruptured hepatocellular adenoma. AB - Hepatocellular adenoma (HA) is an increasingly prevalent benign liver tumor that is strongly associated with use of oral contraceptive medication. The diagnosis is often made after abdominal imaging in female patients with sudden abdominal pain, with or without signs of hemorrhage. Especially larger adenomas are of potential hazard to patients, because of the increased likelihood of rupture or malignant degeneration. Standard treatment of larger adenomas has since long consisted in surgical resection, both for non-ruptured and for ruptured tumors. Although resection is still considered the gold standard, recent reports have advocated initial conservative management. Recently, newer and less invasive methods using selective transarterial embolization have been described that can successfully stop bleeding and even lead to tumor regression. This review addresses different treatment options and recent advances regarding this relatively new condition, focusing mainly on treatment of bleeding and ruptured tumors in an acute setting. A possible algorithm for optimal treatment is presented. PMID- 20357453 TI - Diagnosis and treatment of hepatocellular adenoma in the Netherlands: similarities and differences. AB - BACKGROUND: The diagnosis of hepatocellular adenoma (HA) has a great impact on the lives of young women and may pose clinical dilemmas to the clinician since there are no standardized protocols to follow. We aimed to establish expert opinions on diagnosis and treatment of HA by collecting data from a nationwide questionnaire in the Netherlands. METHODS: A questionnaire was sent to 20 Dutch hospitals known to offer hepatologic and surgical experience on liver tumours. RESULTS: 17 hospitals (85%) responded to the questionnaire. Annually, a median of 52 patients presented with a solid liver tumour. In 15 (88%) hospitals, hepatic adenomas were diagnosed with contrast-enhanced, multiphase spiral CT or MRI. In 2 (12%) hospitals, histology was required as part of a management protocol. Surveillance after withdrawal of oral contraceptives was the initial policy in all clinics. MRI, CT or ultrasound was used for follow-up. Criteria for surgical resection were a tumour size >5 cm and abdominal complaints. In 5 (29%) hospitals, patients were dismissed from follow-up after surgery. In complex cases (e.g. large, multiple or centrally localized lesions, a wish for pregnancy), the treatment policy was highly variable. Pregnancy was not discouraged in 15 hospitals, but in 11 (65%) of these, strictly defined conditions were noted: frequent follow-up, peripheral tumour localization that makes surgery easier if necessary, stable tumour size, and a good informed consent. CONCLUSION: The management of HAs in the Netherlands is rather uniform, except in complex cases in which multiple factors may influence policy. PMID- 20357454 TI - Liver transplantation for benign hepatic tumors: a systematic review. AB - Orthotopic liver transplantation (OLT) has been performed for several benign hepatic tumors. Most of these diseases are usually managed conservatively, or treated by liver resection. OLT might be required when the lesions are symptomatic, diffuse in hepatic parenchyma, causing life-threatening complications or malignant transformation cannot be ruled out. Polycystic liver disease is the most common indication for OLT. We present a review of transplantable benign hepatic lesions to evaluate the need of OLT for these diseases, to summarize in which OLT is a good therapeutic option, and to show the early and long-term survival which might be expected. PMID- 20357455 TI - The influence of drinking pattern, at individual and aggregate levels, on alcohol related negative consequences. AB - AIM: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. METHODS: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. RESULTS: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country's drinking pattern, the less steep the association between the volume of drinking and its consequences. CONCLUSION: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences. PMID- 20357456 TI - Primary and secondary prevention of ischemic stroke. AB - Prevention of stroke and transient ischemic attack includes both conventional approaches to vascular risk factor management (blood pressure lowering, cholesterol reduction with statins, smoking cessation and antiplatelet therapy) and more specific interventions, such as carotid revascularization or anticoagulation for atrial fibrillation. The objective of this review is to discuss effective interventions for optimal primary and secondary stroke prevention. PMID- 20357457 TI - Historical perspectives. AB - The phenomenon of yawning is just as intriguing and fascinating as sleep, yet understanding of its causes and consequences has defied the human mind for centuries. Hippocrates, Sennert, Boerhaave and de Gorter each advanced a theory in his time. From the release of tainted humor to the awakening of animal spirits and improved brain oxygenation, the metaphors that developed from these theories are all characterized by their popular success, which endured until the time of J.M. Charcot and even into our own day. However, starting in the early 19th century, a neuromuscular theory developed from the experimental physiology of Broussais and Flourens, which Dumpert (working in Germany after World War I) explained in detail. Experimental ethology and pharmacology in the 20th century brought the neuromediators and subcortical structures involved in yawning and pandiculation to light. Phylogenetically and ontogenetically primitive, these motor behaviors have been remarkably well preserved during evolution and are nearly universal in vertebrates. They are closer to an emotional stereotypy than to a reflex. Originating in the diencephalon, they appear to exteriorize homeostatic processes in the systems controlling arousal, hunger and sexuality. PMID- 20357458 TI - Popular knowledge and beliefs. AB - Although few things are as common as yawning, it has traditionally held little interest for researchers and enquiring minds of all disciplines. Yawning is a recognized behavior in almost all vertebrates, present throughout life, which often procures a sense of well-being for the yawner. Modern science is still searching for a complete explanation of the mechanisms and purpose of yawning, with debate about its usefulness as a stimulatory mechanism still ongoing. In this paper, we offer an overview of the popular beliefs and myths seen within Arabic, Western and Indian cultures. PMID- 20357459 TI - Yawning throughout life. AB - Yawning is a behavior that begins in the first stages of life. It has not only been observed in infants and in newborns, but also in fetuses of 12-14 weeks' gestational age. Yawning frequency changes over the life span. In preterm infants, the number of yawns decreases between 31 and 40 weeks' postconceptional age, mainly during the day. In this period of life, yawning is an isolated behavior rarely occurring in bursts, and its frequency is quite low with respect to adults. The incidence of yawning seems to increase when children attend elementary school, whereas this is reduced in the elderly. Aged people yawn less than younger ones, mainly during morning and mid-afternoon. In adults, the time course of yawning is associated with the time course of sleepiness, except upon awakening when the high frequency of yawns is not associated with high sleepiness. In adults, yawning frequency increases in the early morning and in the late evening, whereas at the earliest stages of development (fetuses and preterm infants) yawning does not show diurnal variations. Yawning seems to be involved in the modulation of arousal process across the whole life span. In preterm infants, yawning is often followed by motor activation and it is more common during waking than sleep; in adults, yawning occurs mainly at sleep onset and upon awakening. PMID- 20357460 TI - Fetal yawning. AB - Fetal neurobehavioral patterns have been considered as indicators of nervous system development. Moreover, the capacity of 4-dimensional sonography to evaluate complex facial expressions allows recognition of common behaviors with which one can appreciate the prenatal functional development of the central nervous system. Using yawning as an example, we review this interpretation on the basis of knowledge derived from phylogeny and ontogeny. As a flip-flop switch, the reciprocal interactions between sleep- and wake-promoting brain regions allow the emergence of distinct states of arousal. By its ontogenic links with REM sleep, yawning appears to be a behavior which causes arousal reinforcement through the powerful stretching and the neuromuscular connections induced. Yawning indicates a harmonious progress in the development of both the brainstem and the peripheral neuromuscular function, testifying to the induction of an ultradian rhythm of vigilance. The lack of fetal yawn, frequently associated with lack of swallowing (associated or not with retrognathia), may be a key to predicting brainstem dysfunction after birth. PMID- 20357461 TI - Sleep, sleepiness and yawning. AB - This chapter will discuss the relationship between yawning, sleep onset, awakening and sleepiness. Models concerning wake-sleep regulation will be discussed in relation to yawning. Yawning close to sleep, before and after, will be examined in several conditions and populations. Also, the time course of yawning and sleepiness assessed by subjective estimates will be described. PMID- 20357462 TI - Interplay between yawning and vigilance: a review of the experimental evidence. AB - BACKGROUND: Yawning is a phylogenetically old behavior of ubiquitous occurrence. The origin and function of this conspicuous phenomenon have been subject to speculation for centuries. A widely held hypothesis posits that yawning increases the arousal level during sleepiness; thus, providing a homeostatic regulation of vigilance. METHODS: This chapter reviews experimental data on the relationship between yawning and vigilance that allow testing of the components and predictions of this hypothesis. RESULTS: Behavioral studies and electroencephalographic (EEG) recordings of brain activity before and after yawning have provided consistent evidence that yawning occurs during states of low vigilance; thus, substantiating the notion that it is provoked by sleepiness. However, studies analyzing autonomic nervous activity and EEG-based indices of vigilance in yawning subjects did not find specific autonomic activations or increased arousal levels after yawning. CONCLUSIONS: The data therefore do not support an arousing effect of yawning or a role in regulation of vigilance or autonomic tone. PMID- 20357463 TI - The hidden sexuality of the yawn and the future of chasmology. AB - Chasmology is the scientific study of yawning. Though its official history started only recently, its unofficial history stretches back to antiquity. This chapter outlines the history and current state of chasmology, through textual research and analysis, and offers a vision of its future. Particular emphasis is placed upon the author's favorite theory: the hidden sexuality of the human yawn. The 'First Law of Chasmology' states that a yawn occurs: (1) if the yawner cannot do what he would like to do, or (2) if the yawner must do something that he would rather not do. The 'Second Law of Chasmology', which is a special instance of the more general First Law, states that the yawn has an erotic and even a sexual aspect. A critical mass of proof for the validity of this Second Law is derived from various sciences and disciplines, ranging from theology and (the history of) art to ethology and pharmacology. The process of evidencing the Second Law has also established chasmology as an emerging science, i.e. a science that uses the data and information of primary sciences to make a synthesis that transforms and transcends the original scope and results of the auxiliary disciplines. The Second Law allows at least two concrete predictions about future corroborations or refutations in chasmological research. CONCLUSION: Chasmology has a bright future and may yield some surprising results in the near future. PMID- 20357464 TI - Non-human primates: a comparative developmental perspective on yawning. AB - There is a long history of yawning in Old World monkeys being viewed as a form of communication, in particular, as a kind of threat. Yawning in agonistic and tense situations is seen in adult males, in particular, and it varies with male hormonal levels and social status. Experiments are reviewed that demonstrate operant control of the rate of yawning in adult male macaques, using food rewards. This indicates a degree of flexibility in the production of yawning. However, although adult male Old World monkeys often engage in 'canine contests', there is little evidence for the contagious yawning seen in humans. Experiments are reviewed showing that chimpanzees tested under comparable conditions to human adults, namely exposed to video sequences showing yawns, may yawn contagiously to yawn stimuli. Chimpanzees also yawn to computer animations of yawns. There is controversy in the literature over whether other species, including dogs and some monkeys, may also show contagious yawning. Further research is required to address unresolved issues. A hypothesis is put forward that in modern industrial society adults' natural pattern of yawning is inhibited, and that being reminded to yawn by seeing another individual yawn (contagious yawning) can help us to catch up on missed yawns. This would explain the lack of contagious yawning reported in young children and chimpanzees in natural surroundings, as these populations do not have the same social constraints on yawning. PMID- 20357465 TI - Punishment-induced fear modifies the daily course of yawning in rats. AB - A challenge in the study of yawning behavior is understanding the way external factors may modify it. This study investigated whether response-dependent punishment or random punishment decreased yawning by the application of buzzer noise paired with electric shocks in a high-yawning strain of Sprague-Dawley male rats. Yawn rate increased daily in response to the experimental cage, and also to the buzzer noise. Two alternate periods of no punishment and punishment were followed by a final period of buzzer noise occurring alone. Punishment did not diminish yawning significantly in either condition although the yawn rate increased in the following period of no punishment and in the buzzer-noise period, relative to the period of yawn-dependent punishment. Yawn rate increased in the buzzer-noise period relative to the first period of no punishment and first period of random punishment. These findings indicate that there are constraints that impede the suppression of yawning using punishment, and that yawning is a delayed response to fear produced by response-dependent punishment. PMID- 20357466 TI - A thermoregulatory behavior. AB - The existence of yawning across vertebrate species suggests important basic functions, and the spontaneous and involuntary nature of a yawn lends support for it having adaptive significance. Recent research suggests the biological function of yawning among homeotherms is central thermoregulation. Comparative research from birds, rats and humans shows that yawning reduces brain and body temperature, is influenced by the range and direction of ambient temperature change, and is inhibited by methods of behavioral cooling. This research provides strong support for the view that yawning stimulates or facilitates cortical arousal, demonstrating that a yawn is a behavioral response to transient brain hyperthermia, acting to counter intermittent increases in brain temperature and promote thermal homeostasis. This theory is powerful because it not only integrates a great deal of seemingly diverse information about yawning, but it can also be used to generate numerous testable predictions. Applications from this research range from basic physiological understanding to the improved treatment and understanding of diseases associated with thermoregulatory dysfunction. PMID- 20357467 TI - Neurophamacology of yawning. AB - Yawning is a common behavioral event that is observed in humans, as well as other mammals, birds and reptiles. In humans, yawning often occurs just before bed and upon waking up, and is also associated with tedious or boring situations. Although the physiologic roles of yawning have yet to be fully elucidated, the past 50 years of research has led to a much greater understanding of the neuropharmacologic regulation of yawning. While many of the early studies concluded that yawning was primarily driven by changes in cholinergic neurotransmission, we now know that numerous neurotransmitters and neurohormones are involved in the mediation of yawning, including acetylcholine, dopamine, glutamate, serotonin, oxytocin, GABA, opioids, adrenergics, nitric oxide, as well as the proopiomelanocortin-derived peptides ACTH and alpha-MSH. Furthermore, antagonist interaction studies have clearly defined at least 3 distinct neural pathways involved in the induction of yawning, as well as the hierarchical order through which these different neurotransmitter systems interact to regulate yawning. The following sections will discuss the state of knowledge for each of the major neurotransmitters and neurohormones involved in the regulation of yawning, their interactions with one another, and their place in the hierarchical organization of yawning. PMID- 20357468 TI - Yawn, yawn, yawn, yawn; yawn, yawn, yawn! The social, evolutionary and neuroscientific facets of contagious yawning. AB - Contagious yawning is a common phenomenon affecting upwards of 60% of healthy humans. It has also been observed, at a lesser rate, in great apes and other primates. Here I summarize the suggestion that contagious yawning is a primitive expression of social cognition, namely empathy. Susceptibility to contagious yawning is correlated with the speed in recognizing one's own face, theory of mind processing, and is also associated with activation in regions of the brain that have been associated with social cognitive processes. This suggests that contagious yawning may be an evolutionarily old process that begot a higher level of social cognition in certain species. PMID- 20357469 TI - Developmental and comparative perspectives of contagious yawning. AB - Contagious yawning (i.e. yawning triggered by perceiving others' yawning) is a well-documented phenomenon, but the mechanism underlying it is still unclear. In this chapter, I review the current evidence about: (1) developmental studies with typically and atypically developing populations, and (2) comparative studies in non-human animals. Developmental studies have revealed that contagious yawning is disturbed in individuals with autism spectrum disorders, suggesting that contagious yawning may share a developmental basis with the capacity for theory of mind. Comparative studies have suggested that contagious yawning can be observed in non-primate species, such as domestic dogs. As dogs are known to have exceptional skills in communicating with humans, it has also been suggested that contagious yawning may be related to the capacity for social communication. These results from developmental and comparative studies are consistent with the claim that the mechanism underlying contagious yawning relates to the capacity for empathy. PMID- 20357470 TI - Methodological problems in the study of contagious yawning. AB - The recent interest in contagious yawning has raised several challenges as the varied methods of testing have left some unresolved issues. We do not know how differences in key variables affect the observed rates of yawning, and we highlight these as being in need of direct testing. Different researchers analyze their results differently, and we make some recommendations for more rigorous, thorough and informative analyses. Ultimately, problems arise when authors compare studies that used different methods and different analyses without acknowledging how these differences may have affected the results. In these cases, authors make inappropriate comparisons, which lead to conclusions that add confusion to the literature. Our goal in raising awareness of these issues is to generate new experiments and improve the discussion of existing research. With its link to empathy, a more standardized study of contagious yawning may be a useful tool for a variety of disciplines. PMID- 20357471 TI - Exploring yawning with neuroimaging. AB - The neural mechanisms responsible for spontaneous yawning as well as contagious yawning are not well characterized. Neuroimaging is an essential tool for helping to identify the seminal neural structures and their inter-related functions to carry out this complex stereotyped motor program. Studies to date have explored the structural neural correlates of yawning through a series of lesion-based case reports and identified participatory structures at various levels of the central nervous system. Functional neuroimaging methods like fMRI have also shed led on the genesis of contagious yawning, though cohesive models explaining the neural mechanisms of contagious motor programs such as yawning remain limited. PMID- 20357472 TI - Associated movements in hemiplegic limbs during yawning. AB - BACKGROUND: Yawning is phylogenetically ancient and associated with a stereotyped behavioral pattern. OBJECTIVE: To describe the pattern of associated movements observed in hemiplegic limbs during yawning and its relationship to gender, laterality of hemiplegia and muscle tone. MATERIAL AND METHODS: An observational study was designed for 75 patients with newly detected anterior circulatory stroke due to ischemia or hemorrhage in the internal capsule region. The subjects were free from any arthropathy, autoimmune disease, muscular disorders and injury/deformity. RESULTS: There were 48 males and 27 females, whose median ages were 48 and 47 years, respectively. The median yawning onset times after stroke in males and females were 36 and 38 h, respectively. Associated movements in hemiplegic limbs during yawning were minimal and observed in 59 hemiplegics (78.6%); significantly more were seen in males (83%) vs. females (70%), left sided (94%) vs. right-sided hemiplegics (64%), those with hypotonia (87%) vs. hypertonia (61%), and in the upper limbs (91%) vs. lower limbs (83%)and proximal (72%) vs. distal joints (29%), irrespective of limb. CONCLUSION: The appearance of associated movements in hemiplegic limbs indicates the return of ancestral function observed in quadrupeds. However, further studies are needed to ascertain the reasons for such variations and determine how to utilize these movements in rehabilitation programs. PMID- 20357473 TI - Associated diseases. AB - Yawning is a physiological behavior and, as with all such behaviors, its deregulation is indicative of an underlying disorder. This chapter breaks this topic down into the types of yawning (incomplete, absent or excessive) and the direction of causality (triggering or relieving a disorder). PMID- 20357474 TI - A capuchin monkey (Cebus apella) uses video to find food. AB - We examined the ability of capuchin monkeys to use video without immediate visual kinaesthetic feedback as a source of information to guide their action in the 3 dimensional world. In experiment 1, 2 capuchins learned to retrieve food under 1 of 2 different objects in 1 cage after watching the experimenter hiding food under 1 of 2 replica objects while in another cage. Information space and retrieval space were thus separate. The performance criterion was 71% first correct choices in blocks of 24 trials. However, when the subjects watched prerecorded videos of the hiding events, they chose randomly. In experiment 2, we gave the capuchins further trials with video and we enhanced the object shapes by line drawings. One capuchin eventually learned to use the video clips to locate food and he generalized this learning to 2 new objects. PMID- 20357475 TI - Correlation between first-trimester maternal serum markers, second-trimester uterine artery doppler indices and pregnancy outcome. AB - AIMS: The aim of this study was to assess the correlation between first trimester maternal serum free beta-human chorionic gonadotropin (fBHCG), pregnancy associated plasma protein A (PAPPA), second-trimester uterine artery (UA) Doppler measurements and adverse pregnancy outcomes. METHODS: Serum levels of PAPPA and fBHCG were determined at the first trimester, and patients underwent bilateral UA Doppler assessments at 20-25 weeks of gestation. A serum PAPPA level <0.4 MoM was termed as low and the abnormal Doppler findings were the presence of bilateral notches and RI >0.52 (mean) or unilateral notch and RI >0.66 (90th percentile). RESULTS: Mean PAPPA level was significantly lower in cases with unilateral or bilateral notches (1.09; 0.79 and 0.80 MoM for 0, 1 and 2 notches, p < 0.001). Fifty-two cases (12.8%) had a low PAPPA level; in this group the incidence of abnormal Doppler was significantly higher (34.6 vs. 18.4%, p = 0.011). In the presence of abnormal Doppler in a case with a low serum PAPPA the risk of pregnancy-induced hypertension (OR = 4.56, p = 0.0067), low birth weight (OR = 6.8, p = 0.0002) and the risk of at least one complication (OR = 7.6, p = 0.00001) were significantly high. CONCLUSION: Combination of first- and second trimester findings might improve the efficiency of screening for pregnancy complications. PMID- 20357476 TI - Studying the joint effects of population stratification and sampling in case control association studies. AB - Population stratification (PS) is referred to the systematic difference in allele frequencies between subpopulations in a population. It could cause a false positive conclusion in a case-control association study, where the association is due to the structure of the underlying population, not a disease-associated locus. In this paper, we study the joint effects of PS and data sampling when the genetic effect is null. The level of the PS effect depends on the variation of the baseline genotype frequency across subpopulations and matching effectiveness of the sampling. In the case of simple random sampling (SRS), the matching effectiveness equals the inverse of the variation of the disease odds, and thus the PS bias is null under constant disease risk. However, if the latter condition holds but the sampling is not SRS, the bias may still exist. The magnitude of the bias increases as the deviation between the true sampling and SRS increases. We also derive bounds for the bias. If the bounds are approximately known or estimable, we show that this information can be used to compute a conservative p value for the usual association test. We give two real examples to demonstrate the application of the new method. PMID- 20357477 TI - Genome-wide linkage scan maps ETINPH gene to chromosome 19q12-13.31. AB - OBJECTIVE: Essential tremor (ET), one of the most common neurological disorders, comprises uncontrollable tremor, usually in the upper extremities. Idiopathic normal pressure hydrocephalus (iNPH) features ventricular enlargement in the absence of elevated intracranial pressure; its three cardinal symptoms are gait impairment, incontinence, and dementia. iNPH is among the most common medical problems in the older population. To date, the genetic etiologies of ET and iNPH remain largely elusive. METHODS: We previously identified a large kindred in which the affected members developed ET in adolescence or young adulthood and iNPH when elderly, in that case called ETINPH. Employing two different genotyping microarrays and two- or multipoint linkage analysis strategies, genome-wide linkage scans were performed. RESULTS: We mapped the ETINPH locus to chromosome 19q12-13.31. Fine-mapping in this region revealed a maximum two-point lod score of 2.8 at rs2023865 and a maximum multipoint lod score of 17.9 at rs9304878. By haplotype construction, a (conservatively) approximately 17-cM critical region from SNP rs11084582 to SNP rs7258420 was defined. This region contains several neuronal genes that constitute tantalizing etiological candidates for ETINPH. CONCLUSION: The importance of uncovering the genetic etiology of this disorder is irrefutable, as such a discovery could offer valuable insights into ET, iNPH, and related neurological conditions. PMID- 20357478 TI - Feasible and successful: genome-wide interaction analysis involving all 1.9 x 10(11) pair-wise interaction tests. AB - The Genome-Wide Association Study (GWAS) is the study design of choice for detecting common genetic risk factors for multifactorial diseases. The performance of full Genome-Wide Interaction Analyses (GWIA) has always been considered computationally challenging. Two-stage strategies to reduce the amount of numerical analysis require the detection of single marker effects or prior pathophysiological hypotheses before the analysis of interaction. This prevents the detection of pure epistatic effects. Our case-control study in idiopathic generalized epilepsy demonstrates that a full GWIA is feasible through use of data compression, specific data representation, interleaved data organization, and parallelization of the analysis on a multi-processor system. Following extensive quality control of the genotypes, our final list of top interaction hits contains only pairs of interacting SNPs with negligible marginal effects. The TOP HIT interaction was between a SNP-pair intragenic to gene DNER (chr 2) and gene CTNNA3 (chr 10). Both of these genes are functionally involved in neuronal migration, synaptogenesis, and the formation of neuronal circuits. Our results therefore indicate a possible interaction between these two genes in epileptogenesis. Results from GWAS are beginning to reveal a 'missing heritability' in complex traits and diseases. Systematic, hypothesis-free analysis of epistatic interaction (GWIA) may help to close this increasingly recognized gap in heritability. PMID- 20357479 TI - Characterization of the T-cell epitopes of the major peach allergen Pru p 3. AB - BACKGROUND: Pru p 3 is the major peach allergen recognized by more than 90% of peach-allergic individuals of the Mediterranean area. Identification of the dominant Pru p 3 T-cell epitopes can improve our understanding of the immune responses against this protein and could be helpful in the development of hypoallergenic immunotherapy. For this purpose, we examined the phenotypes, specificities and cytokine secretion profiles of proliferating T cells in response to Pru p 3 in peach-allergic individuals. METHODS: Peripheral blood mononuclear cells from 15 peach-allergic patients were incubated with Pru p 3. The proliferation of antigen-specific T-cell lines (TCLs) was assessed by tritiated methylthymidine incorporation. T-cell epitopes were identified by analyzing the reactivity of TCLs against 8 overlapping peptides spanning the entire length of Pru p 3. We characterized the phenotype of Pru-p-3-specific TCLs by flow cytometry and analyzed their production of interleukin (IL) 4 and gamma interferon (IFN-gamma) by ELISA. RESULTS: Ninety-two Pru-p-3-specific TCLs were isolated (stimulation index > or =5). These TCLs proliferated mainly in response to Pru p 3(12-27) and Pru p 3(57-72). Pru-p-3-specific TCLs were mainly CD4+ (81%) and expressed cell surface CD30. In addition, TCLs produced high levels of IL-4 and low levels of IFN-gamma, indicating a Th2 phenotype. CONCLUSIONS: Two immunodominant T-cell-reactive regions of Pru p 3 were identified: Pru p 3(12-27) and Pru p 3(57-72). These peptides showed a differential ability to elicit a Th2 response. Taken together, our results provide a better understanding of the immunological T-cell reactivity against Pru p 3. PMID- 20357480 TI - Alpha-melanocyte-stimulating hormone plays an important role in the onset of pollinosis in a pollen allergy mouse model. AB - BACKGROUND: alpha-Melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that controls melanogenesis in pigmentary cells. In addition, its potent immunomodulatory activity has been recently described in cutaneous inflammatory disorders. However the mechanism of such pollen allergies remains to be elucidated. The purpose of this study was to investigate the role of alpha-MSH in a murine model of pollen allergy. METHODS: Eight-week-old male BDF-1 mice were sensitized with Cry j I. After the last intranasal antigen, the number of sneezes was counted for 5 min. In addition, the serum levels of IgE and neuronal hormones were measured by ELISA. The expression of IgA, melanocortin receptor 1 (MC1R) and MC5R in the trachea were also observed by immunohistochemistry. RESULTS: Both the concentration of alpha-MSH and adrenocorticotropin in plasma increase in pollen allergy model mice. Furthermore, MC5R increased in the trachea; however, MC1R did not increase in the trachea. In addition, the changes in sneezing and IgA expression in the pollen allergy model mice were suppressed by alpha-MSH antibody treatment, but they remained unchanged after MC1R antagonist (agouti) treatment. CONCLUSIONS: These results indicate that sneezing due to pollen allergy is associated with an increased concentration of alpha-MSH and the expression of MC5R. PMID- 20357481 TI - Induction of CD4+CD25+Foxp3+IL-10+ T cells in HDM-allergic asthmatic children with or without SIT. AB - BACKGROUND: Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-beta(1), may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy. METHODS: PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5-2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-gamma and TGF-beta(1 )in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay. RESULTS: Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-beta were lower and the amounts of IFN-gamma were higher in the SIT group compared with the asthma group. CONCLUSION: There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4(+)CD25(+)Foxp3(+) Treg cells. PMID- 20357482 TI - Glucocorticoids inhibit double-stranded RNA-induced thymic stromal lymphopoietin release from keratinocytes in an atopic cytokine milieu more effectively than tacrolimus. AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes in skin lesions in atopic dermatitis and bronchial epithelial cells in asthma, plays a key role in allergic diseases. Double-stranded RNA (dsRNA) stimulates keratinocytes to release TSLP in vitro. OBJECTIVE: To examine the potential of glucocorticoids and calcineurin inhibitors to suppress dsRNA-induced release of TSLP from keratinocytes. METHODS: Primary human kerarinocytes were stimulated with dsRNA in the presence of IL-4, IL-13 and TNF-alpha. TSLP release was measured by ELISA. The effects of glucocorticoids and 2 calcineurin inhibitors, cyclosporin A and FK506/tacrolimus, were analyzed. RESULTS: The glucocorticoids inhibited dsRNA-induced release of TSLP. The inhibitory effect became saturated (50-70% reduction) at concentrations higher than 10(-10)M. Cyclosporin A inhibited the release of TSLP by 50-60% at 10(-5) and 10(-4)M. FK506 had no effect at 10(-5)M or less, but almost completely inhibited the release of TSLP at 10(-4)M. No synergistic effect was obtained with a glucocorticoid plus either of the calcineurin inhibitors. An additive inhibitory effect was obtained with a glucocorticoid plus 10(-5)M cyclosporin A. Glucocorticoid inhibited dsRNA-induced TSLP transcription in the absence of Th2/TNF cytokines. CONCLUSIONS: Glucocorticoids inhibited the dsRNA-induced release of TSLP in the atopic cytokine milieu at much lower concentrations than calcineurin inhibitors, suggesting that they could be effective in the treatment of atopic dermatitis when exogenous or endogenous dsRNA is involved in the pathogenesis. In addition, the in vitro system established in this study would be useful for screening of therapeutic reagents which target TSLP expression. PMID- 20357483 TI - Low molecular weight glutenins in wheat-dependant, exercise-induced anaphylaxis: allergenicity and antigenic relationships with omega 5-gliadins. AB - BACKGROUND: Adults suffering from wheat-dependant, exercise-induced anaphylaxis (WDEIA) develop IgE directed against wheat omega5-gliadins (major allergens for this allergy) and against wheat low-molecular weight glutenin subunits (LMW-GS). However, the ability of LMW-GS to trigger an inflammatory response is still unknown. It also remains to be determined if IgE from these patients bind the same epitopes on LMW-GS and omega5-gliadins or if the epitopes are independent. METHODS: WDEIA patients were selected and skin prick tests (SPTs) were performed on them using commercial gluten, wheat flour extracts, prolamin fractions and a purified natural LMW-GS P42. The IgE-binding ability of natural and recombinant wheat prolamins was verified by immunoblot experiments. Cross-reactivity between LMW-GS and omega5-gliadins was studied by immunoblot inhibition experiments, using purified natural omega5-gliadin as an inhibitor. RESULTS: Patients developed positive SPTs with natural LMW-GS fractions and/or with the purified LMW-GS P42. Natural and recombinant LMW-GS were highly reactive with patient IgE in immunoblot experiments, as was omega5-gliadin. However, differences in reactivity were evident within the LMW-GS group. Except for one recombinant LMW GS (P73), IgE cross-reactivity between LMW-GS and natural omega5-gliadin was only partial. CONCLUSION: LMW-GS are able to promote local inflammation and they share common epitopes with omega5-gliadins. The nature of these epitopes is discussed. LMW-GS also carried specific epitopes, completely independent from the omega5 gliadin epitopes. Thus, LMW-GS behaved partly as independent allergens. PMID- 20357484 TI - Airborne fungi induce nasal polyp epithelial cell activation and Toll-like receptor expression. AB - BACKGROUND: The nasal epithelium is the first barrier encountered by airborne allergens and is an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and airway diseases. The aim of the study was to evaluate fungal protease activity during cytokine production in nasal polyp epithelial cells and to determine the expression of Toll-like receptor (TLR) mRNA by fungi. METHODS: Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria and Aspergillus. Interleukin-8 (IL-8) and granulocyte macrophage colony-stimulating factor (GM CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase polymerase chain reaction for the TLR mRNA expression of the nasal epithelial cells was performed. Cytokine production was inhibited with protease inhibitors and anti-human TLR antibodies. RESULTS: The fungi enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. When nasal epithelial cells were activated by the fungi, TLR2, TLR3 and TLR4 mRNAs were more strongly expressed than in the nonactivated cells. Cytokine production was inhibited by protease inhibitors and anti-human TLR4 antibodies. CONCLUSIONS: The results of this study showed that fungi interacted with nasal epithelial cells and enhanced the production of cytokines and TLR mRNA expression. The cytokine production was related to the protease in fungi and TLR4. PMID- 20357485 TI - Safety of cefuroxime as an alternative in patients with a proven hypersensitivity to penicillins: a DAHD cohort survey. AB - OBJECTIVE: In patients sensitized to beta-lactams, a safe beta-lactam alternative is often needed. The objective was to assess the safety of cefuroxime in patients with a proven beta-lactam allergy. DESIGN: Using the Drug Allergy and Hypersensitivity Database cohort, patients with a proven beta-lactam allergy and tested for cefuroxime between September 1996 and April 2007 were selected. The European Network of Drug Allergy recommendations were followed. Prevalence of sensitization to cefuroxime (as an alternative) was established in patients with a proven beta-lactam allergy. RESULTS: Amongst the 650 subjects tested, 143 (22.0%) presented at least one beta-lactam sensitization other than cefuroxime [39-27.3% male, median age at test 44.0 (32.0-56.0) years]. One hundred and eighteen (82.5%) were sensitized to penicillins, 8 (5.6%) to cephalosporins and 17 (11.9%) to both penicillins and cephalosporins. Nine (6.3%) patients were sensitized to cefuroxime (6 diagnosed by provocation test): 5 (55.6%) in the penicillin-only allergic group and 4 (44.4%) in the penicillin and cephalosporin allergic group. Prevalence of cefuroxime hypersensitivity reaction in patients sensitized to beta-lactams was 6.3% (95% CI 2.3-10.3%) and in those sensitized to penicillin 4.2% (95% CI 0.6-7.9). This rate decreased to 2.9% (95% CI 0-6.9) in patients with prior histories involving a penicillin only (without any history involving an unknown beta-lactam). CONCLUSION: Cefuroxime appeared to be a safe alternative in beta-lactam-allergic patients after testing. The risk of giving cefuroxime being not null, a thorough drug allergy work-up, including provocation test, is still needed. PMID- 20357486 TI - Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response. AB - BACKGROUND: Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. METHODS: Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments. RESULTS: Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. CONCLUSIONS: The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts. PMID- 20357487 TI - Exhaled breath temperature increases during mild exacerbations in children with virus-induced asthma. AB - BACKGROUND: Exhaled breath temperature (EBT) has been suggested as a non-invasive surrogate marker of airway inflammation in asthma. The aim of the study was to evaluate differences in EBT between periods of controlled disease and during exacerbations in children with virus-induced asthma. METHODS: Twenty-nine children (aged 6-14 years) with a history of intermittent, virus-induced asthma were included in this case-control study. Cases presented with a common cold and/or mild exacerbation of asthma, while controls were free of asthmatic or common cold symptoms during the previous 6 weeks. A baseline questionnaire was obtained. Atopy assessment, central temperature and a spirometric measurement were recorded. EBT was measured with a new device (Delmedica, Singapore). A nasal wash (for identification of common respiratory viruses) was obtained. RESULTS: Twenty-four children (12 from each group) completed the study. Groups were homogeneous with respect to baseline characteristics. PCR revealed the presence of a virus in 3 out of 17 controls and 10 out of 12 cases (17.6 and 83.3%, respectively, p = 0.002). The most commonly identified virus was rhinovirus (3/3 controls and 7/10 cases, p = 0.02). EBT values were significantly higher for cases (34.91 +/- 0.62 degrees C) compared to controls (34.18 +/- 1.1 degrees C, p = 0.032). No important differences were observed in the increase rate of EBT (Deltae degrees T) between groups. CONCLUSIONS: Changes in airway inflammation during virus-induced asthma exacerbations are reflected in EBT changes. These preliminary data suggest a possible role of EBT measurements in the assessment of airway inflammation in children with virus-induced asthma. PMID- 20357488 TI - Changes in high-sensitivity C-reactive protein in serum and exhaled breath condensate after intensive exercise in patients with allergic asthma. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) in asthmatics depends on the presence of allergic inflammation. This study was performed to assess the possible association of EIB with low-grade systemic inflammation, whose presence was revealed in asthmatic patients. METHODS: The study was conducted in a group of 24 asthmatics (14 with EIB, 10 without EIB) and 8 healthy volunteers. Changes in serum and exhaled breath condensate (EBC) high-sensitivity C-reactive protein (hs-CRP) levels induced by intensive exercise were determined. Moreover, the possible correlation of these measurements with the results of other tests used in the diagnosis of asthma as well as laboratory tests commonly associated with asthma were investigated. RESULTS: In asthmatic patients with EIB, a statistically significant increase in hs-CRP levels both in serum and EBC after an exercise test was observed. Twenty-four hours after the exercise test in the group of asthmatics with EIB, a statistically significant increase in exhaled nitric oxide (F(ENO)), serum eosinophil cationic protein (ECP) concentrations and bronchial hyperreactivity to histamine was revealed. A statistically significant correlation between the maximum increase in hs-CRP levels both in serum and EBC after exercise and either baseline F(ENO) and an increase in serum ECP or F(ENO) 24 h after exercise in the group of asthmatics with EIB was revealed. CONCLUSIONS: We show that, as a result of intensive exercise leading to bronchoconstriction, an increase in serum and EBC hs-CRP occurs. Our observations could suggest that in asthmatic patients, as a consequence of exercise-induced bronchoconstriction, an intensification of low-grade systemic inflammation can be observed. PMID- 20357489 TI - Immunoglobulin E sensitization to cross-reactive carbohydrate determinants: epidemiological study of clinical relevance and role of alcohol consumption. AB - BACKGROUND: The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal. OBJECTIVE: To investigate the relationship of alcohol consumption with CCD sensitization, the role of alcohol dehydrogenase gene polymorphisms, and the clinical consequences of CCD sensitization. METHODS: Serum-specific IgE sensitization (> or =0.1 kU/l) to a CCD (the N-glycan from bromelain) was assessed in 1,197 adults participating in a population-based study in Copenhagen, Denmark. Alcohol consumption and atopic symptoms (rhinitis, asthma and oral allergy syndrome) were assessed by questionnaire. Examinations included skin prick tests (SPTs), qualitative multiallergen IgE test (Phadiatop), methacholine bronchial hyperreactivity, eosinophil cationic protein and alcohol dehydrogenase (ADH) gene polymorphisms. RESULTS: Alcohol consumption was significantly associated with CCD sensitization and this was particularly evident in SPT-negative individuals. The fast metabolizing allele of the ADH1b polymorphism was significantly associated with CCD sensitization in alcohol drinkers. CCD sensitization was associated with atopic symptoms, but associations attenuated markedly when adjusting for SPT reactivity. CONCLUSIONS: Our results suggest that the positive association between alcohol consumption and CCD sensitization is universal and not specific to certain populations. The observed association between the ADH1b polymorphism and CCD sensitization may support that alcohol is causally related to the risk of CCD sensitization. The observed association between CCD sensitization and atopic phenotypes did not appear to be independent of SPT reactivity indicating limited significance of CCD sensitization per se. PMID- 20357490 TI - Change in referral diagnoses and diagnostic delay in hypogammaglobulinaemic patients during 28 years in a single referral centre. AB - BACKGROUND: The classical clinical manifestation of untreated immunoglobulin deficiency comprises predominantly recurrent and complicated respiratory tract infections. Before the 1980s, little was known about the clinical manifestation of immunodeficiency in the general medical population, and also the availability of serum immunoglobulin laboratory determination was not sufficient, leading to a significant diagnostic delay. METHODS: We have analysed the diagnostic delay and referral diagnoses in patients in whom any form of primary hypogammaglobulinaemia had been diagnosed at our department, which was established in 1981. RESULTS: Comparing the diagnostic delay in the 1980s (19 patients, median 5.5 years), the 1990s (37 patients, median 3.5 years) and the years 2001-2008 (33 patients, median 1 year), a significant decrease was observed (p < 0.05, Spearman's correlation coefficient). Also, the median number of pneumonia episodes during the diagnostic delay decreased from 5 in the 1980s, to 1 in the 1990s and to 0 in the period of 2001-2008 (p < 0.05, Spearman's correlation coefficient). While in the 1980s 17 of the 19 patients had pneumonia in their past history, in the period of 2001-2008 only 13 of the 33 patients were concerned. CONCLUSIONS: Our observation documents improved awareness of immunodeficiencies among physicians. It is supposed that earlier diagnosis will prevent complications, improve the quality of life and even survival of hypogammaglobulinaemic patients. PMID- 20357491 TI - An elevated value on drug-induced lymphocyte stimulation test for immunoglobulin is an immunological abnormality of Kawasaki disease. AB - BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis in childhood. Currently, treatment with 2 g/kg of intravenous immunoglobulin (IVIG) is recommended. Previously we had encountered a patient with KD who showed persistent fever and a severe eruption after IVIG treatment. Using a drug-induced lymphocyte stimulation test (DLST), he was positive for an immunoglobulin product. The aim of this study was to clarify the importance of a positive value for the DLST for immunoglobulin products in KD patients. METHODS: Subjects were 30 confirmed KD patients treated with IVIG at the Kagoshima Medical Association Hospital. DLST values were compared between patients with additional events and those without additional events using the stimulation index (SI = value of (3)H thymidine absorption with antigen/without antigen). Additional events were defined as symptoms observed after IVIG that were considered unexplainable by the symptoms of KD alone. RESULTS: DLST results were evaluated in 13 patients with additional events and 17 patients without additional events. Elevated DLST values were observed not only in patients with additional events but also in those without additional events. Elevated SI values were observed in the initial 14 days after IVIG and the SI values in this period were significantly higher than those after day 14 (initial 14 days, n = 20, 194 +/- 112%; after day 14, n = 10, 117 +/- 66%, p = 0.010). CONCLUSIONS: Elevated SI values of DLST for immunoglobulin products are not related with additional events. Our results show they may represent one of the immunological abnormalities of KD. PMID- 20357492 TI - Multiple integrations of human T-lymphotropic virus type 1 proviruses in the engrafted cells from the asymptomatic carriers in NOD/SCID/gammacnull mice. AB - OBJECTIVES: Successful engraftment of human T-lymphotropic virus type 1 (HTLV-1) infected cells and a marked increase of proviral DNA loads (PVLs) in non-obese diabetic/severe combined immunodeficient (NOD/SCID)/gammac(null) (NOG) mice have been reported. Whether the increased PVL in transplanted mice is due to the new infection of HTLV-1 was examined. METHODS: Mononuclear cells from 3 NOG mice with primary engraftment from asymptomatic HTLV-1 carriers were transplanted into a second group of NOG mice. HTLV-1 PVL, proviral integration by fluorescence in situ hybridization assay, expression of viral antigen, and T-cell clonality were analyzed. RESULTS: The PVLs in the secondarily transplanted NOG mice were significantly higher than those of primarily transplanted NOG mice. Multiple signals of HTLV-1 proviruses in the nucleus of the infected cells were revealed by fluorescence in situ hybridization analysis. Expression of HTLV-1 tax/rex mRNA and antigen was observed. The variety of T-cell clones was limited in the transplanted NOG mice. CONCLUSIONS: Multiple proviral integrations were considered to be due to the new infection from HTLV-1-infected cells to the other cells. Only a certain fraction of T cells seemed to have selectively survived in NOG mice after engraftment. PMID- 20357493 TI - Evaluation of a 6-year highly active antiretroviral therapy in Chinese HIV-1 infected patients. AB - OBJECTIVE: To evaluate the long-term efficacy and tolerability of nevirapine (NVP)-based regimens in the treatment of human immunodeficiency virus (HIV) infected Chinese patients in routine clinical practice. METHODS: From October 2002 to May 2004, 57 HIV-1-infected patients commenced antiretroviral therapy (ART), and were followed up to December 2008. These antiretroviral-naive patients, who originally received two nucleoside reverse transcriptase inhibitors and NVP, had HIV RNA levels, T lymphocyte subsets and safety parameters assessed over 6 years. RESULTS: Of the 57 patients, 34 patients participated in the long term follow-up. After 5-6 years, >60% of the patients had HIV RNA levels <50 copies/microl, and the median increase in CD4 cell counts from baseline was 329 cells/microl. gamma-Glutamyl transferase increased in 17 patients (29.8%); serum cholesterol and triglyceride levels were elevated in 15 patients (26.3%), and 25.0% (6/24) of the patients developed lipodystrophy (mainly females). Grade 3/4 adverse events occurred in 3 cases. CONCLUSION: ART with NVP-based regimens suppressed HIV viremia and produced continued CD4 cell increases in a majority of subjects for 6 years. Safety and tolerance were good with no unexpected long-term toxicity. Though based on a small group, this study demonstrates durable effects of ART in Chinese patients. PMID- 20357494 TI - Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free-living population of men and women. AB - BACKGROUND/AIMS: The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. METHODS: Caucasian men (n = 96) and women (n = 217) 20-29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. RESULTS: Among men, consumption of sucrose was 60 +/- 6, 48 +/- 4, and 39 +/- 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 +/- 4, 53 +/- 2, and 44 +/- 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. CONCLUSIONS: These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption. PMID- 20357495 TI - Renal magnesium handling is not subject to developmental programming. AB - Developmental programming of hypertension, induced by maternal protein restriction, is associated with enhanced urinary excretion of sodium and calcium in the rat. Although calcium and magnesium are reabsorbed via different pathways, renal calcium excretion often parallels magnesium output. Accordingly, the aim of the current study was to assess magnesium handling in rats exposed to a low protein (LP) diet in utero. Wistar rats were fed a control (18%) or LP (9%) diet throughout pregnancy; offspring were weaned onto standard rat chow and studied at 4 weeks of age. Renal clearance measurements were made in both volume expanded and euvolaemic anaesthetised rats; 24-hour magnesium turnover was also assessed in conscious animals. Plasma and total body magnesium content were measured. Total (U(Mg)V) and fractional excretion (FE(Mg)) of magnesium did not differ between control and LP rats under any of the experimental conditions. Neither plasma nor total body magnesium content differed between control and LP rats. Thus the hypercalciuria of LP rats is not mirrored by an increase in renal magnesium excretion. These data suggest that renal magnesium handling is not affected by developmental programming. PMID- 20357496 TI - Alterations of lipid metabolism in chronic nephropathies: mechanisms, diagnosis and treatment. AB - Nephropathic subjects show an increased tendency to develop cardiovascular diseases, mainly as the consequence of several risk factors including increased oxidative stress, inflammation, physical inactivity, anemia, vascular calcification, and endothelial dysfunction. The alterations in lipid metabolism represent a relatively lesser important cause of genesis and progression of atherosclerosis. Unfortunately, in these patients the atherogenic potential of dyslipidemia may depend more on apolipoproteins than on lipid abnormalities, and may not always be recognized by measurement of plasma lipids alone. The aim of this review was therefore to analyze the main lipid alterations that can occur in nephropathic patients, as well as their causes and their effects on the cardiovascular system. The clinical evidence and recommendations for the use of lipid-regulating drugs in patients with chronic kidney disease, nephrotic syndrome, in patients undergoing hemo- and peritoneal dialysis and in transplanted patients was also reviewed. Moreover, we analyzed the link between dyslipidemia and kidney disease onset and progression and the role of statins in preventing it. PMID- 20357498 TI - Frequency and type of chromosomal abnormalities in childhood acute lymphoblastic leukemia patients in Kuwait: a six-year retrospective study. AB - OBJECTIVE: To characterize the frequency of genetic profiles in pediatric acute lymphoblastic leukemia (ALL) patients in Kuwait. SUBJECTS AND METHODS: This review presents the general cytogenetic characteristics of 164 pediatric patients diagnosed as having ALL in a 6-year period. Chromosomal and fluorescence in situ hybridization studies were made on bone marrow aspirates at diagnosis and during different stages of the disease. RESULTS: Recurring aberrations, observed in 123 (75%) patients, included hyperdiploidy (n=68, 41%), tetraploidy (n=12, 7.3%), hypodiploidy (n=2, 1.2%), TEL-AML1 fusion (n=11, 7%), mixed-lineage leukemia rearrangement (n=6, 3.6%), t(9;22) (n=4, 2.4%), t(1;19) (n=3, 1.8%), t(8;14) or t(8;22) (n=2, 1.2%), +21 (n=2, 1.2%), del(6) (n=2, 1.2%) and miscellaneous abnormalities (n=9, 5%). The highest observed numerical chromosome abnormality was high hyperdiploidy in 89 patients (54%) with abnormal karyotype while the TEL AML fusion was the highest observed structural abnormality. CONCLUSION: This study showed that clonal anomalies detected in pediatric ALL have shown correlations between specific abnormalities and clinicobiological characteristics of the patients. PMID- 20357499 TI - Corticosteroid nonprescription use: a cross-sectional hospital-based study in Basrah. AB - OBJECTIVE: To study the prevalence and attitude of using nonprescription corticosteroids (oral or parenteral formulation of glucocorticosteroids) in Basrah, Iraq. METHODS: A face-to-face model structured interview was used to collect information from 682 patients between January 2006 and December 2008. The following information was obtained: age, gender, marital status, smoking, drinking of alcohol, occupation, educational level, social class and place of residence. RESULTS: Of the 682 (2.6%) subjects using nonprescription corticosteroids most were females: 471 (69%); married: 567 (83%); of low social class: 430 (63.1%); lived in the city center: 475 (69.6%). The majority (569, 83.5%) thought that corticosteroid use was safe and 463 (68.0%) did not feel guilty for using such medications. About half of them (377, 55.3%) were still using drugs at the time of presentation. Three hundred and fifty-seven (52.4%) reported that physicians advised them for the first time to use corticosteroids and the remaining 325 (42.2%) used it to become beautiful or marry. Three hundred and sixty-four (53.4%) patients obtained the drug from the pharmacy and 252 (36.9%) from street vendors. Weight gain was the main indication for use in 342 (50.1%) patients. Almost all had some features of corticosteroid side effects. CONCLUSION: This study showed high use of nonprescription corticosteroid in Basrah, Iraq. We therefore recommend educational programs to alert the population of the untoward side effects of corticosteroids. PMID- 20357497 TI - Principles and practice of nonpharmacological interventions to reduce cardiometabolic risk. AB - The components of the metabolic syndrome, including prediabetes, prehypertension and dyslipidemia, represent prodromal stages of major cardiometabolic disorders. Lifestyle interventions have been shown to ameliorate or prevent the progression of individual components of the metabolic syndrome. The specific interventions utilized in randomized controlled studies often include dietary modification and physical activity. The effects of smoking cessation and the reduction of psychosocial stress on cardiometabolic risk factors need to be studied more. Because of the close concordance between the metabolic syndrome and multiple cardiometabolic diseases, the adoption of an effective lifestyle change upon initial recognition of the metabolic syndrome can be expected to delay or prevent the future development of sequelae such as diabetes, hypertension, and atherosclerotic cardiovascular and cerebrovascular diseases. Such a nonpharmacological approach to primary prevention and disease interruption carries enormous public health significance. Meeting the challenge of an implementation of effective lifestyle change at the community level requires (a) a system for the identification of at-risk populations, (b) an optimization of the knowledge base and practices of health care providers, and (c) a piloting of targeted biobehavioral intervention programs. Once identified, persons and communities at risk for cardiometabolic disorders can be empowered through increased health and nutritional literacy, the promotion of lifestyle interventions, provision of community resources, and pertinent legislative action that rewards preventive behavior. This paper reviews landmark studies that demonstrate the principles of nonpharmacological approaches to the reduction of cardiometabolic risk. We also discuss the physiological and emerging molecular genetic mechanisms that underlie the efficacy of lifestyle interventions. PMID- 20357500 TI - Evaluation of urine collection methods for the diagnosis of urinary tract infection in children. AB - OBJECTIVE: To evaluate the accuracy of urine sample collection methods among children suspected of having urinary tract infections. SUBJECTS AND METHODS: Four methods for urine sample collection were evaluated in 1,067 children aged 0-16 years with suspected urinary tract infections over 2 months at Dr. Sami Ulus Children's Hospital. Within 30 min of collection, all specimens were sent to the laboratory, refrigerated and processed according to standard hospital microbiological procedures. Urine samples were analyzed using routine culture techniques. RESULTS: At initial sending of the urine culture, 617 (57.8%) had negative culture results, 145 (13.6%) had positive culture results, and 305 (28.6%) had evidence of bacterial contamination. Clean catch specimens showed a contamination rate of 14.3% and urethral catheterization specimens showed a similar contamination rate (14.3%). However, urethral catheterization was preferred in only a small number of cases (n=7). Suprapubic aspiration was also used in a small number of cases (n: 11) and the contamination rate for suprapubic aspiration was 9.1% (n: 1/11). The contamination rate for sterile urine bag was 43.9%, significantly higher than the other methods (p<0.001). CONCLUSION: Suprapubic aspiration showed the lowest contamination rate and sterile urine bag showed the highest contamination rate among 4 methods of urine sample collection. Contaminated specimens, needed to be repeated and this procedure increased the cost of urine culture. In conclusion, measures should be taken to reduce the contamination rate in our center. This is an area where further investigation is required. PMID- 20357501 TI - Significance of antinuclear antibodies and rheumatoid factor in patients with advanced peripheral arterial disease. AB - OBJECTIVE: To determine whether or not elevated titers of antinuclear antibodies (ANA) and/or rheumatoid factor (RF) are associated with patients with advanced peripheral arterial disease (PAD). SUBJECTS AND METHODS: A cross-sectional study was done between September 2005 and December 2006. Fifty-eight patients with clinical and angiographic evidence of PAD and 41 controls were studied. Controls had no documented history of peripheral, coronary or cerebral vascular disease. All subjects were screened for metabolic syndrome and C-reactive protein (CRP) as risk factors for peripheral vascular disease. Additionally, all were tested for anti-mitochondrial, anti-neutrophil cytoplasmic and anti-smooth muscle antibodies; those with positive results were excluded. ANA and RF were measured in sera from cases and controls. RESULTS: One case and 3 controls had positive anti-smooth muscle antibodies and were therefore excluded from statistical analysis. Metabolic syndrome was significantly more prevalent in patients than controls (p<0.05). Mean CRP level was 4.78+/-7.70 and 2.65+/-3.86 mg/dl in cases and controls, respectively (p=0.021). ANA were detected at a titer of >or=1:40 in 6 (10.5%) of the advanced PAD patients but none of the controls; the difference was not statistically significant. RF was less prevalent in cases than controls (p<0.05). CONCLUSION: RF and ANA do not appear to be associated with PAD in a Kuwaiti population. PMID- 20357502 TI - Primary hepatic actinomycosis. AB - OBJECTIVES: To present a case of primary hepatic actinomycosis. CLINICAL PRESENTATION: A-40-year-old man was admitted to the general surgery clinic with a 1-month history of abdominal pain and weight loss. Liver transaminase, bilirubin levels and white blood cell counts were increased. Abdominal ultrasound and CT revealed cystic lesions with necrotic debris involving the posterior segment of the right lobe of the liver and the medial segment of the left lobe. INTERVENTION: The patient underwent surgery under general anesthesia. On exploration, three cavities were found within the liver containing necrotic material. Surgical debridement and drainage was performed. Histopathological examination revealed actinomycotic colonies with a surrounding suppurative granulomatous reaction. The patient was treated with penicillin for 3 months. CONCLUSION: This case showed that histological examination of biopsy or surgical material or anaerobic cultures was needed for definitive diagnosis and that hepatic actinomycosis should be included in the differential diagnosis of solitary or multiple hypodense liver lesions. PMID- 20357503 TI - Association of estrogen receptor-alpha gene polymorphism with pathogenesis of osteoporosis in Korean vegetarian men. AB - OBJECTIVE: The purpose of this study was to investigate the association between two genetic polymorphisms (PvuII and XbaI restriction fragment length polymorphisms, RFLPs) of the estrogen receptor-alpha (ER1) gene and the quantitative ultrasound (QUS) parameters at the calcaneus. SUBJECTS AND METHODS: Two hundred and sixty-six Korean vegetarian men, mean age 50.9+/-12.0 years (range 26-80), were studied. Polymorphisms at the ER1 gene sites and the cross sectional associates of genetic factors with calcaneal QUS parameters including broadband ultrasound attenuation (BUA) and the speed of sound (SOS) were analyzed by RFLPs using polymerase chain reaction. RESULTS: The distribution of PvuII and XbaI RFLPs in the ER1 gene was as follows: PP 11.6%, Pp 47.2%, pp 41.2%, XX 1.2%, Xx 24.4% and xx 74.4%. After adjusting for potential confounding factors such as age and body mass index, two genetic polymorphisms of the ER1 gene were independently associated with BUA, SOS and stiffness index at the calcaneus of our subjects. The QUS measurements of the subjects with the xx genotype were higher than those of the subjects with an Xx genotype, while the QUS measurements of the subjects with a Pp genotype were significantly lower than those of the subjects with PP or pp genotypes (p<0.05). CONCLUSION: The results suggest that the PvuII and XbaI RFLPs of the ER1 gene may be genetic factors that affect QUS at the calcaneus. PMID- 20357504 TI - Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients. AB - OBJECTIVE: To investigate the effects of Nigella sativa seed supplementation on symptom levels, polymorphonuclear leukocyte (PMN) functions, lymphocyte subsets and hematological parameters of allergic rhinitis. SUBJECTS AND METHODS: Twenty four patients randomly selected from an experimental group of 31 (mean age 34 years) sensitive to house dust mites with allergic rhinitis and a control group of 8 healthy volunteers (mean age 23 years) were treated with allergen-specific immunotherapy in conventional doses for 30 days. After a month of immunotherapy, 12 of the 24 patients and the 8 healthy volunteers were given N. sativa seed supplementation (2 g/day orally) for 30 days. The remaining 12 patients continued only on immunotherapy during the same period. The other 7 patients were given 0.1 ml saline solution subcutaneously once a week as a placebo. The symptom scores, PMN functions, lymphocyte subsets and other hematological parameters were evaluated before and after all treatment periods. RESULTS: There was a statistically significant increase in the phagocytic and intracellular killing activities of PMNs of patients receiving specific immunotherapy, especially after the addition of N. sativa seed. The CD8 counts of patients receiving specific immunotherapy plus N. sativa seed supplementation significantly increased compared to patients receiving only specific immunotherapy. PMN functions of healthy volunteers significantly increased after N. sativa seed supplementation compared to baseline. CONCLUSION: N. sativa seed supplementation during specific immunotherapy of allergic rhinitis may be considered a potential adjuvant therapy. PMID- 20357505 TI - Investigation of a one-time phenol application for pilonidal disease. AB - OBJECTIVE: To investigate wound healing rates and postoperative recovery of patients after a one-time phenol application for pilonidal disease. SUBJECTS AND METHODS: A total 30 consecutive patients with chronic pilonidal disease ranging from midline to complex sinuses were enrolled in the study. No preoperative laboratory examinations or bowel preparation were required. No antibiotic prophylaxis or sedation was used. A small incision was made on the midline and hair/debris in the sinuses was removed. A cotton swab with saturated phenol was moved into the cavity and the phenol was left for 2 min. No special dressing was necessary and patients left the hospital immediately afterwards. Patients filled out a daily questionnaire for 7 days. We did not intervene in the wounds with a second phenol application or curettage during the observation period. Wounds were inspected at weekly intervals for 2 months. RESULTS: At the end of the third day, 97% of the patients were pain-free and 100% of the patients were free from analgesics. Time off work was 2 days for most patients (93.3%). Twenty-eight (93.3%) patients were satisfied with the procedure, they found it easy and painless and suggested the procedure to other patients. Twenty-five (83%) patients were asymptomatic at the end of 2 months' observation and the remaining 5 patients had unhealed sinuses. Mean time for wound healing was 25 days (range 10-63 days). There were 4 recurrences after a mean of 14 months' follow-up and the overall success rate was 70%. CONCLUSIONS: A one-time phenol application was an effective treatment for pilonidal disease with acceptable wound healing rates, less postoperative pain and less time off work. Hence it can be an alternative treatment modality. PMID- 20357506 TI - 5- and 10-year recurrence rate is the new gold standard in pilonidal sinus surgery benchmarking. PMID- 20357507 TI - Simultaneous detection and differentiation of Staphylococcus species in blood cultures using fluorescence in situ hybridization. AB - OBJECTIVE: To develop a new protocol for the simultaneous detection and differentiation of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) in blood cultures using fluorescence in situ hybridization (FISH), without cultivation and biotyping. MATERIALS AND METHODS: Oligonucleotide probes were used to target the variable regions of the 16S rRNA of S. aureus and CoNS, the probes were labeled with fluorochrome Cy3 (red signal) and fluorescein isothiocyanate (green signal), respectively. It is not possible to design one probe that will hybridize to all CoNS species. Therefore, in this study two differentially labeled probes (STA and SAU) were mixed and used to detect and differentiate S. aureus from CoNS rapidly in a single smear. Samples of 189 positive blood cultures with Gram-positive cocci in clusters and 11 Gram-positive cocci in chains or pairs were included. RESULTS: The FISH assay showed 91.8% sensitivity and 100% specificity for S. aureus and 100% sensitivity and 93.3% specificity for CoNS when hybridized with STA and SAU probes. Meanwhile, the assay showed 91.8% sensitivity and 100% specificity for S. aureus and 100% sensitivity and 90% specificity for CoNS, when hybridized with the SAU probe only. CONCLUSION: Our data showed that the FISH technique was suitable for the simultaneous detection and differentiation of Staphylococcus sp. in blood cultures. PMID- 20357508 TI - The value of transvaginal ultrasonography in the endometrial evaluation of breast cancer patients using tamoxifen. AB - OBJECTIVE: To estimate the value of transvaginal ultrasonography (TVU) in evaluating the endometrium in breast cancer patients on tamoxifen, and to investigate the relationship between TVU and histologic endometrial findings in these patients. SUBJECTS AND METHODS: 107 breast cancer patients taking tamoxifen were included in this study. TVU was performed twice for each patient: prior to starting tamoxifen therapy and 1 year after taking tamoxifen. An endometrial thickness of >or=5 mm was considered abnormal. Endometrial biopsy was performed at the same time the 2nd TVU was done. The patients were divided into 2 groups: symptomatic (group A) and asymptomatic (group B), based on whether or not there was abnormal vaginal bleeding. RESULTS: 31 patients (29%) were symptomatic, while the remaining 76 (71%) were asymptomatic. The endometrial thickness increased after 1 year of taking tamoxifen from 4.84+/-0.4 mm to 6.34+/-2.1 mm in group A and from 4.73+/-0.3 mm to 5.67+/-1.95 mm in group B (p>0.05). Endometrial biopsy revealed 77 (71.96%) atrophic endometria and 21 (19.62%) polyps. A comparison between the 2 groups showed a significant difference in patients with endometrial atrophy and atypical hyperplasia. Patients who had an endometrial thickness of >5 mm had a significantly higher prevalence of atypical hyperplasia (p=0.003) and polyps (p=0.041). The sensitivity, specificity, positive predictive and negative predictive values of TVU were 63.3, 28.57, 25.67 and 66.66%, respectively. CONCLUSION: Our study showed a discrepancy between TVU and endometrial biopsy findings, due to the specific histology of the endometrium in breast cancer patients using tamoxifen. Due to this discrepancy, TVU alone is not an effective screening test for endometrial pathology and its application alone might lead to an undesirably high frequency of invasive diagnostic procedures. PMID- 20357509 TI - Spontaneous osteochondroma resolution in a young female: imaging and histopathological findings. AB - OBJECTIVE: To report the first operated and histopathologically studied case of spontaneously resolving solitary osteochondroma. CASE PRESENTATION AND IDENTIFICATION: An 18-year-old girl presented with leg pain of 2 months' duration. She had been diagnosed to have a proximal tibial osteochondroma since the age of 9 years. Excision biopsy of the tumor remnant and its surrounding tissue was done after CT and MRI imaging. CONCLUSION: The spontaneous resolution of this case could have been due to simultaneous interruption of blood supply to the tumor and its cartilaginous cap or hyperemia around the tumor. PMID- 20357510 TI - A rare cause of small bowel transection: metastatic lung cancer. AB - OBJECTIVE: To present a case of small bowel perforation due to metastatic lung cancer. CASE PRESENTATION AND INTERVENTION: A 78-year-old male patient, who had been diagnosed with lung cancer 3 months earlier, presented to our clinic with acute abdominal pain. He underwent emergency laparotomy. At surgery, there was a circumferential lesion encompassing the ileum with complete transection. There was no obvious macroscopic appearance of metastatic disease. The involved bowel segment was resected and an ileostomy was performed. Postoperative pathologic analysis confirmed metastatic squamous cell carcinoma metastasis to the ileum, arising from the patient's lung cancer. CONCLUSION: This case report showed that small bowel metastases should always be considered in the differential diagnosis of lung cancer patients presenting with acute abdominal pain. PMID- 20357512 TI - 'Refeeding syndrome' in a Kuwaiti child: clinical diagnosis and management. AB - OBJECTIVE: To report a case of refeeding syndrome in a Kuwaiti child, its clinical presentation and management. CLINICAL PRESENTATION AND INTERVENTION: A 13-month-old Kuwaiti boy presented with acute severe malnutrition in the form of marasmic kwashiorkor. On admission, blood sugar and serum electrolytes were normal but on the 3rd day he developed typical biochemical features of refeeding syndrome in the form of hyperglycemia, severe hypophosphatemia, hypokalemia, hypocalcemia and hypomagnesemia. The child then received treatment appropriate for refeeding syndrome in the form of lower calorie intake with gradual increase, as well as supplementation of electrolytes, thiamine and vitamins and he eventually made a safe recovery. CONCLUSION: This case showed that during rehabilitation of a malnourished child, a severe potentially lethal electrolyte disturbance (refeeding syndrome) can occur. Careful monitoring of electrolytes before and during the refeeding phase was needed and helped to detect this syndrome early. We suggest that slow and gradual calorie increase in the 'at risk' patient can help prevent its occurrence. PMID- 20357511 TI - A case of community-onset meningitis caused by hospital methicillin-resistant Staphylococcus aureus successfully treated with linezolid and rifampicin. AB - OBJECTIVE: To report a relatively rare presentation of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a previously healthy boy in Kuwait. CLINICAL PRESENTATION AND INTERVENTION: A 14-year-old boy presented with a 2 weeks' history of headache and fever with increasing severity. He developed photophobia and double vision 2 days prior to his hospital visit and received ceftriaxone for 6 days prior to admission to the hospital. There was no history of head trauma or neurosurgical operation. Lumbar puncture revealed a slightly turbid cerebrospinal fluid with pleocytosis and greatly reduced glucose, elevated protein level and on culture grew MRSA. Staphylococcal chromosome cassette mec (SCCmec) typing revealed that it belonged to SCCmec type III and sequence type 238 (ST238-SCCmec-III). Polymerase chain reaction screening for the presence of Panton-Valentine leukocidin (PVL) genes yielded a negative result; all these findings were consistent with hospital-acquired MRSA. He was treated with intravenous linezolid and rifampicin for 2 weeks, made good response and was discharged home fully recovered and well. CONCLUSION: Hospital MRSA should be considered in the differential diagnosis of the causative agents of community onset meningitis in healthy patients even without predisposing factor. PMID- 20357513 TI - Advanced glycation end products and acute myocardial infarction. AB - OBJECTIVE: The aim of this study was to analyse the dynamics of advanced glycation end products (AGEs) after acute myocardial infarction (MI). SUBJECTS AND METHODS: Blood samples were taken from 20 non-diabetic patients with acute MI on the 1st, 2nd, 3rd and 5th day after the onset of symptoms. Serum AGE levels were estimated spectrofluorometrically. RESULTS: A marked decrease in the AGE specific fluorescence was observed, especially between the 1st and the 2nd days after MI. CONCLUSION: The findings of this study tend to contradict the suggestion that AGEs are relatively stable markers of carbonyl stress. Although the reason for this is currently unknown, this observation may have implications for ongoing studies of AGEs in cardiovascular diseases. PMID- 20357514 TI - Epidemiology in a globalising world: new challenges for researchers. PMID- 20357515 TI - Analyses of diagnostic patterns at 30 Alzheimer's disease centers in the US. AB - BACKGROUND: The US Alzheimer's Disease Centers (ADCs) (n = 30) recently created a uniform data set. We sought to determine which variables were most important in making a diagnosis, and how these differed across ADCs. METHODS: A cross sectional analysis of first visits to ADCs via polytomous logistic regression. We analyzed subjects with complete data (n = 7,555, 89%), and also used multiple imputation to infer missing data. RESULTS: There were 8,495 subjects; 50, 26, and 24% were diagnosed as normal, having mild cognitive impairment (MCI), or mild Alzheimer's disease [Clinical Dementia Rating (CDR) score <1], respectively. The model using 7,555 subjects was 86% accurate in predicting diagnosis. Important predictors were physician-reported decline and the CDR sum of boxes, followed by 4 cognitive tests (Mini Mental State Examination, Category Fluency Tests, Logical Memory Test, Boston Naming Test). Multiple imputation revealed Trail Making Test B to be additionally important. Consensus versus single-clinician diagnoses were 2-3 times more likely to result in MCI than normal diagnoses. Excluding clinical judgment variables, functional assessment and psychiatric symptoms were important additional predictors; model accuracy remained high (78%). There were significant differences between centers in the use of different cognitive tests in making diagnoses. CONCLUSIONS: We recommend creating a hypothetic data set to use across ADCs to improve diagnostic consistency, and a survey on the use of raw or adjusted cognitive test scores by different ADCs. PMID- 20357516 TI - Individual life expectancy estimation using validated prognostic scores for patients with cancer of unknown primary. AB - PURPOSE: To implement 3 published prognostic scores in an independent set of patients with cancer of unknown primary (CUP), and compare their performance on individual life expectancy prediction. PATIENTS AND METHOD: The survival of 430 consecutive patients with CUP was measured after they had allocated to their prognostic group (good prognosis vs. poor prognosis) according to each prognostic score. Using a 2 x 2 contingency table, we measured the sensitivity, specificity, positive predictive value (PPV) and accuracy of each score in predicting individual outcome (survival <90 days or >180 days). RESULTS: The median overall survival was 189 days (1-4,801 days). Survival was <90 days in 143/421 cases and >180 days in 208/413 cases. The three PPVs were within the same range for prediction of survival <90 days (from 43 to 49%) as well as for prediction of survival >180 days (from 70 to 80%), and underestimate individual life expectancy of 40-50% of the patients. None of the 3 scores appeared significantly better. CONCLUSION: The main finding of this retrospective analysis is that the published prognostic scores cannot be used for rational decision making. PMID- 20357517 TI - Use of thymidine kinase gene-modified endothelial progenitor cells as a vector targeting angiogenesis in glioma gene therapy. AB - OBJECTIVE: The poor prognosis of patients with glioma is due to infiltrative growth of glioma cells, which correlates with their ability to induce angiogenesis. Tumor angiogenesis is supported by the mobilization and functional incorporation of endothelial progenitor cells (EPCs). The aim of this study was to propose the use of gene-modified EPCs as a vector system that allowed systemic gene delivery into multiple areas of tumor angiogenesis for glioma therapy. METHODS: Thymidine kinase (TK) gene-modified EPCs were mixed with glioma cells or human umbilical vein endothelial cells (HUVECs) at varying ratios for ganciclovir in vitro. Cell proliferation was evaluated by MTT assay, and apoptosis was examined by annexin-V and phosphatidylserine (propidium iodide) staining. EPCs were injected via tail vein into nude mice bearing glioma, and EPC incorporation into the tumor was determined immunohistochemically. The antitumor effects of TK gene-modified EPCs in vivo were evaluated by apoptosis assay and microvessel density analysis. RESULTS: TK gene-modified EPCs exerted a potent bystander effect on glioma cells and HUVECs by induction of apoptosis via caspase activation in vitro. EPCs incorporated preferentially into glioma vasculatures. Furthermore, TK gene-modified EPCs clearly augmented the antitumor effect by inhibition of angiogenesis following repeated intravenous injection in vivo. CONCLUSION: The results indicate the feasibility of EPC-based gene delivery into disseminated areas of tumor angiogenesis as a rational strategy for glioma gene therapy. PMID- 20357518 TI - Acquired resistance to temozolomide in glioma cell lines: molecular mechanisms and potential translational applications. AB - Treatment for glioblastoma multiforme includes the alkylating agent temozolomide combined with ionizing radiation. Persistent O6-guanine methylation by temozolomide in O6-methylguanine methyl transferase negative tumors causes cytotoxic lesions recognized by DNA mismatch repair, triggering apoptosis. Resistance (intrinsic or acquired) presents obstacles to successful temozolomide treatment, limiting drug efficacy and life expectancy. Two glioma cell lines, SNB19 and U373, sensitive to temozolomide (GI(50) values 36 and 68 microM, respectively) were exposed to increasing temozolomide concentrations (1-100 microM). Variant cell lines (SNB19VR, U373VR) were generated that displayed acquired temozolomide resistance (GI(50) values 280 and 289 microM, respectively). Cross-resistance to mitozolomide was observed in U373VR cells only. In clonogenic and MTT assays, methylguanine methyltransferase (MGMT) depletion using O6-benzylguanine sensitized U373VR cells to temozolomide, indicating the resistance mechanism involves MGMT re-expression. Indeed, Western blot analyses revealed MGMT protein in cell lysates. In SNB19VR cells, down regulation of MSH6 message and protein expression may confer temozolomide tolerance. Inhibition of poly(ADP-ribose) polymerase-1 (a key base excision repair (BER) enzyme) partially restored sensitivity, and DNA repair gene arrays demonstrated up-regulation (>5-fold) of BER gene NTL1 in SNB19VR cells. In conclusion, we have developed two glioma cell lines whose distinct mechanisms of acquired resistance to temozolomide, involving expression of MGMT, or inactivation of DNA mismatch repair and recruitment of BER enzymes, are consistent with clinical observations. These cell lines provide valuable models for the development of strategies to combat temozolomide resistance. PMID- 20357519 TI - Formalin fixation could interfere with the clinical assessment of the tumor-free margin in tumor surgery: magnetic resonance imaging-based study. AB - OBJECTIVES: The tumor-free margin in bone and soft-tissue cancer is a key factor for subsequent treatment. While flattening and shrinkage of specimens after formalin fixation have been described in breast cancer, there are no data for bone and soft tissue sarcoma. Fixation could interfere with the accuracy of the assessment of the tumor-free margin. METHODS: The influence of formalin fixation was assessed on forelimb specimens in a preclinical porcine model. The specimens were subjected to magnetic resonance imaging before and after formalin fixation. Weight, width and height of the specimen were measured and different consecutive volumes (total, muscles, bones and fatty tissue) were obtained by segmentation. RESULTS: After formalin fixation, the weight increased, total volume and muscle volume slightly increased while bone did not change and fatty tissue decreased. The width of the specimens increased while their height decreased. CONCLUSIONS: Formalin fixation caused slight muscle expansion, fatty tissue shrinkage and flattening of the specimen. These changes could interfere with the assessment of the tumor-free margin in clinical practice. PMID- 20357520 TI - A target-specific electrode and lead design for internal globus pallidus deep brain stimulation. AB - In nearly all deep brain stimulation (DBS) applications, the same quadripolar electrode design is used for different anatomical targets even if shape and volume differences exist between nuclei. Taking into account the electrode location within the internal globus pallidus (GPi) and the size of the GPi, 2 electrodes were designed in order to improve the therapeutic benefit, to minimize side effects from DBS and to obtain a more homogeneous electric field distribution. The electrodes were evaluated numerically by using a stereotactic model measuring the correlation between the electric field and the GPi. The model was applied to 26 dystonodyskinetic patients who underwent surgery for a bilateral lead implantation into the posteroventral part of the GPi. The designed electrodes produced a more homogeneous distribution of the electric field than the quadripolar electrode. PMID- 20357521 TI - Defining the intercommissural plane and stereotactic coordinates for the Basal Ganglia in the Gottingen minipig brain. AB - The intercommissural line joining the anterior and posterior commissures defines stereotactic coordinate systems used in functional neurosurgical procedures. Such coordinate systems are generally accepted in humans and nonhuman primate experimental settings and provide high stereotactic precision and reproducibility. The ethical concern surrounding the use of nonhuman primates has motivated and helped popularize the use of the Gottingen minipig as an alternative experimental model for experimental functional neurosurgery. We investigated the position and variability of the intercommissural line in the minipig brain using in vivo MRI. From these data, standard coordinates for the minipig basal ganglia were estimated. We found the variability of the intercommissural line to be small in the Gottingen minipig and the variability of the basal ganglia structures to the mid-commissural point to be minor. PMID- 20357522 TI - Infections and hardware salvage after deep brain stimulation surgery: a single center study and review of the literature. AB - AIMS: Infection of hardware is a serious complication after deep brain stimulation (DBS), as this may result in additional surgery, cost and loss of treatment benefit for the patient. We report the incidence and management of infections after DBS in a single institution over the past 11 years. METHODS: A database of 270 patients with 484 implants was used in the study. Incidence, clinical characteristics and management of infections were analyzed. RESULTS: The overall infection rate was 9.3% (25/270) by patients and 6.8% (33/484) by episode/implants. The median time of infection after implantation was 64 days. Only 7/33 episodes (21.2%) occurred within 30 days after surgery, 22/33 episodes (66.7%) within 6 months and 28/33 episodes (84.8%) within 12 months. There was no age difference between infected and noninfected patients, while comorbidities were more frequent in the former. Infection rates before and after January 2003 were 14.3 and 4.9%, respectively. The rate of complete and partial hardware salvage was 30.3 and 21.2% while that of complete hardware removal was 48.5%. Patients with deep purulent infections and patients with Staphylococcus aureus as the causative organism were more likely to have their hardware removed. CONCLUSIONS: The incidence of hardware infections declined significantly over time. Improvements in hardware and implantation techniques may be responsible. Hardware can often be completely or partly saved in infected patients. PMID- 20357523 TI - Effect of various surgical modalities in recurrent or persistent trigeminal neuralgia. AB - BACKGROUND/AIMS: In recurrent or persistent idiopathic trigeminal neuralgia (TN) after initial operation, additional surgical procedures may be required. There are numerous articles reporting the outcomes of additional surgical treatment and it is unclear how best to treat patients with recurrent or persistent TN. We evaluated the subsequent therapeutic options for recurrent or persistent TN. METHODS: The study was a retrospective study. The authors reviewed 29 patients (15 female/14 male) who underwent retreatments for recurrent or persistent symptoms after an initial operation. RESULTS: The mean follow-up duration was 56.4 months (range 12-78.7) from final treatment. Patients underwent a mean of 2.3 retreatments with a mean period of 26 months (range 1-72) between treatments. Final treatments were as follows: microvascular decompression (MVD) in 12 patients, percutaneous rhizotomy in 10, and radiosurgery in 7. Of the 29 patients, after final treatments, 9 patients (31%) achieved excellent results and 15 (52%) good results. Failure results were seen in 17% of patients with recurrent TN. CONCLUSION: In this study the authors demonstrate that percutaneous rhizotomy is recommended for most patients with recurrent pain after MVD, and MVD can be effective in patients with a history of failed percutaneous procedures. Radiosurgery can be utilized to treat those that have not responded to other surgical modalities. PMID- 20357524 TI - [Primary rectal malignant melanoma with rapid progression after complete resection]. PMID- 20357525 TI - [Clinical approach to incidental pancreatic cystic lesions]. AB - Cystic lesions of the pancreas are being incidentally recognized with increasing frequency and become a common finding in clinical practice. Despite of recent remarkable advances of radiological and endoscopic assessment and a better understanding of natural history of certain subgroups of cystic lesions, differentiating among lesions and making an optimal management plan is still challenging. A multimodal approach should be performed to evaluate incidentally detected cystic lesions. Emerging evidence supports selective nonoperative management for the majority of patients with cystic lesions, but, for those in whom a suspicion of malignancy remains, surgery is indicated. Concerning long term follow-up, there is limited data to support the ideal modality, intensity, and duration. Therefore, evidence-based guidelines for the diagnosis, management, and follow-up of cystic lesions of the pancreas should be established. PMID- 20357526 TI - [Clinical significance of incidentally detected eosinophilic esophagitis with pathologic review]. AB - BACKGROUND/AIMS: Eosinophilic esophagitis (EE) is a chronic inflammatory disorder characterized by abnormal dense eosinophilic infiltration of esophageal mucosa and results in dysphasia and food impaction. EE is being increasingly recognized in adults. The prevalence is largely unknown. This study was performed to evaluate the detection rate of EE diagnosed based on pathologic criteria and to define the clinical characteristics of EE in Korea. METHODS: We reviewed biopsy specimen of the 1,609 patients who underwent esophageal biopsy from January 2006 till August 2008. The presence of more than 20 eosinophils per high power field in biopsy specimens was considered cases of EE. Clinical information and endoscopic findings were obtained. RESULTS: 7 (0.4%) patients were diagnosed as EE based on pathologic criteria retrospectively. Clinical symptoms were epigastric pain (43%), regurgitation (29%), dyspepsia (14%), and no symptom (14%). Endoscopic findings were whitish exudates or granules (57%), esophageal polyp (29%), and hyperemic change (14%). Two patients received treatment. One patient with bronchial asthma improved after treatment with inhaled corticosteroid, and one patient improved after 8 week proton pump inhibitor therapy. CONCLUSIONS: Eosinophilic esophagitis was found in 0.4% of the total esophageal biopsied cases. Our results suggest that Korean patients with eosinophilic esophagitis showed symptoms mimicking gastroesophageal reflux disease and atypical endoscopic findings. Therefore, regardless of the gross appearance of the mucosa, meticulous diagnostic approaches are needed for patients with swallowing difficulty and lack of response to proton pump inhibitor. PMID- 20357527 TI - [Change of Clostridium difficile colitis during recent 10 years in Korea]. AB - BACKGROUND/AIMS: Our clinical experience and recent published literatures suggest that Clostridium difficile colitis (CDC) has become more common and potentially more pathogenic in recent years. The aim of study was to evaluate changes in the epidemiological features of CDC in hospitalized patients in Korea. METHODS: We retrospectively reviewed all patients of CDC diagnosed at Kangnam St. Mary Hospital from 1998 to 2007. CDC was defined as having a positive C. difficile cytotoxicity assay, or endoscopic or pathologic evidence of CDC. RESULTS: A total of 189 cases (male 73, female 116, mean age 63.3 years) of CDC were diagnosed during the study period. The prevalence of CDC increased from 1.9/10,000 patient admissions in 1998-1999 to 8.82/10,000 patient admissions in 2006-2007. One hundred sixty three indication for cases (86.2%) of patients identified a prior use of antibiotics in the 2 months preceding diagnosis. The most common antibiotic use was prophylactic use during perioperational period (33.3%) followed by pneumonia (23.3%). The overall response rate to initial antibiotics was 82.7%. One hundred seventy two (91%) patients were initially treated with metronidazole. The response rate was 84.3%. All patients with initial failure to metronidazole were successfully treated by vancomycin. The response rate of vancomycin as first treatment was 80%. Three deaths were associated with CDC despite the use of combination of metronidazole and vancomycin. CONCLUSIONS: The prevalence of CDC in hospitalized patients in Korea significantly increased from 1998 to 2007. PMID- 20357528 TI - [The incidence and clinical features of Clostridium difficile infection; single center study]. AB - BACKGROUND/AIMS: Clostridium difficile is the predominant cause of nosocomial diarrhea. Recently, the incidence of Clostridium difficile infection (CDI) increases in Europe and North America. A retrospective study was performed to evaluate the change of incidence and clinical features of CDI in Korea. METHODS: From January 2003 to December 2008, inpatients diagnosed with CDI in Seoul Paik hospital were enrolled. The diagnosis of CDI was made when patients complained diarrhea with any positive results in C. difficile toxin assay, stool culture, or endoscopy. The incidence, recurrence rate, and clinical features were compared between early period (2003-2005) and late period (2006-2008). RESULTS: The incidence of CDI was 21.73 cases per 10,000 admitted patients in early period group, and significantly increased to 71.71 cases per 10,000 admitted patients in late period group (p < 0.01). The hospital stay duration at the time of CDI diagnosis was shorter in late period group. Cephalosporin had the highest ratio as the causative antibiotics of CDI. However, there was no difference in recurrence rate between early and late period groups. Recurrence associated clinical factor was serum albumin level. CONCLUSIONS: The incidence of CDI showed increasing tendency during recent 6 years. The awareness of increasing disease burden is the first step in control of CDI. PMID- 20357530 TI - [A case of segmental colitis associated with diverticular disease]. AB - Segmental colitis associated with diverticular disease (SCAD) is a colonic inflammatory disorder with localized non-granulomatous inflammation at sigmoid colon, and associated with colonic diverticulosis. SCAD is an apparently uncommon disorder in Western. We experienced a rare case of SCAD in a 46-year-old woman who visited the hospital due to abdominal discomfort. Colonoscopic examination showed multiple sigmoid diverticula in association with a segment length colitis. Colonoscopic biopsies of the sigmoid colon demonstrated cryptitis and crypt abscess along with chronic inflammatory cells infiltration. The biopsies of the rectum was histologically normal. The patient was given the diagnosis of SCAD and treated with oral mesalamine. This is the first case of SCAD reported in Korea. PMID- 20357529 TI - [Seroprevalence of IgG anti-HAV in hospital employees below 40 years old]. AB - BACKGROUND/AIMS: Hepatitis A is an acute infectious disease transmitted by fecal oral route. As the incidence of hepatitis A has been increased in Gwangju and Chonnam province of Korea recently, the number of hepatitis A patients in hospital employees has also increased. Thus, we investigated the seroprevalence of IgG anti-HAV in hospital employees below 40 years old. METHODS: We analysed the seroprevalence of anti-HAV IgG from 1,002 Chonnam national university hospital employees (men: 190, women: 812) who were below 40 years old. The age group was divided by 5 years; 21-25 years old 199 (19.9%), 26-30 years old 426 (42.5%), 31-35 years old 215 (21.5%), 36-40 years old 162 (16.1%). RESULTS: Overall seropositive rate of IgG anti-HAV was 32.8% (329/1,002). The seropositive rate of men was 40.5% (77/190) and that of women was 31.0% (252/812). The seropositive rates of each age group were 1.5% (3/199) in 21-25 years old, 21.6% (92/426) in 26-30 years old, 48.4% (104/215) in 31-35 years old, and 80.2% (130/162) in 36-40 years old. The seropositivity rate of the high risk group (doctors, nurses, technicians) was 28.9% (234/809). CONCLUSIONS: The seropositive rate of IgG anti-HAV was the lowest in early twenties of hospital employees and below 50% in early thirties. Therefore, hepatitis A vaccination may be warranted in the hospital employees below the early thirties. PMID- 20357531 TI - [A case of non-occulsive mesentery ischemia with pulmonary embolism due to protein C deficiency]. AB - Protein C is an important physiological anticoagulant factor. Protein C deficiency has been linked to venous thrombosis at unusual sites, including the cerebral and mesenteric veins. Hereditary protein C deficiency is inherited primarily as an autosomal dominant trait with incomplete penetrance. Protein C and S deficiencies are known to increase the risk of venous thrombosis and pulmonary thromboembolism. Testing for protein C levels and function is necessary for the detection of both type I and type II protein C deficiency. In this article, we report a case of pulmonary embolism and mesentery ischemia due to type 1 protein C deficiency. PMID- 20357532 TI - [A case of pleural effusion associated with acute hepatitis A]. AB - Hepatitis A virus (HAV) infection is common in developing countries, including Korea. It can be accompanied by extrahepatic complications such as renal failure, arthritis, and vasculitis. Pleural effusion is a very rare complication of HAV infection, which has been reported usually in children, and has benign clinical courses. Here we report a case of pleural effusion with ascites which occurred in an adult hepatitis A patient. A 26-year-old-woman presented generalized myalgia and fever and was diagnosed as acute hepatitis A. Despite of the improvement of laboratory findings, fever and cough persisted. Pleural effusion newly appeared on the serial chest radiologic images. After the fever settled down, the pleural effusion resolved spontaneously at 13th day of admission. PMID- 20357533 TI - [A case of Fitz-Hugh-Curtis syndrome in a male]. AB - Fitz-Hugh-Curtis syndrome has been described as focal perihepatitis accompanying pelvic inflammatory disease caused by Neisseria gonorrhea and Chlamydia trachomatis. The highest incidence occurs in young, sexually active females. However, the syndrome has been reported to occur infrequently in males, according to the foreign literature. The predominant symptoms are right upper quadrant pain and tenderness, and pleuritic right sided chest pain. The clinical presentation is similar in men and women. In women, the spread of infection to liver capsule is thought to occur directly from infected fallopian tube via the right paracolic gutter. In men, hematogenous and lymphatic spread is thought to be postulated. Recently, we experienced a case of Fitz-Hugh-Curtis syndrome occurred in a man. As far as we know, it is the first report in Korea, and we report a case with a review of the literature. PMID- 20357534 TI - [Is Clostridium difficile infection increasing in Korea?]. PMID- 20357535 TI - Focuses on the organization of our healthcare systems. PMID- 20357536 TI - Opinions: When healthcare is bad for your health. PMID- 20357537 TI - CHSRF knowledge transfer: Policy priorities for primary healthcare improvement: a national conversation. PMID- 20357538 TI - CIHI survey: bariatric surgery in Canada. AB - Bariatric surgery is a treatment option for obese patients when weight-reduction strategies such as lifestyle modifications and pharmacotherapy fail. To date, bariatric surgery has resulted in sustained weight loss; the resolution of diabetes for some patients has also been observed. The objective of this study was to explore changes in-patient bariatric surgery delivery in Canada between 2004-2005 and 2008-2009. PMID- 20357539 TI - ICES reports: Canada's response to pandemic H1N1 influenza: the collection of individual-level data at the point of vaccination. PMID- 20357540 TI - Accelerating excellence report: Releasing time to care. AB - Saskatchewan's Health Quality Council (HQC) was launched in 2003 with a mandate to not only measure and report on healthcare but also work with a range of partners to improve the province's health system. In late 2007, HQC's board decided it was time for Saskatchewan to reinvent its healthcare system, using the highest-performing systems in the world as its model. And in 2008, HQC launched Accelerating Excellence, a multi-level program to rethink, redesign and renew healthcare. To help maintain momentum and show other provinces whether high performing healthcare can be achieved in Canada, HQC is documenting its journey toward high-performing healthcare. This second article in this series discusses the Releasing Time to Care program. PMID- 20357541 TI - Insight: In conversation with Richard Alvarez. Interview by Ken Tremblay. PMID- 20357542 TI - Creating community governance: a view from the inside. PMID- 20357543 TI - Enhancing lives together: reviewing the process of an organizational amalgamation. AB - The amalgamation between two hospitals creates a transition period of significant change, uncertainty and complexity. It is a challenging time within an organization that needs to be managed effectively. This article outlines the integration process and eight-step framework used during an amalgamation of an acute hospital organization and a post-acute hospital. The initial process evaluation and lessons learned are also presented. PMID- 20357544 TI - Strategic implementation and accountability: the case of the long-term care alliance. AB - A group of chief executives of long-term care homes formed an alliance in order to tap the resources residing within their management teams. Adopting a strategic implementation project based on a framework of accountability, the executives were able to better understand the uncertainties of the environment and potentially structure their strategic implementation to best use scarce resources. The framework of accountability allowed the homes to recognize the need for a strong business approach to long-term care. Communication improved throughout the organizations while systems and resources showed improved utilization. Quality became the driving force for all actions taken to move the organizations toward achieving their visions. PMID- 20357545 TI - Time for a paradigm shift: managing smarter by moving from data and information to knowledge and wisdom in healthcare decision-making. AB - Senior decision-makers in the Canadian healthcare system have to continuously make significant, and complex, policy and program decisions. However, it appears that, often, the evidence they have available is fairly simple descriptive information, collected for operational purposes. Trying to solve complex problems with fairly simple data may lead to suboptimal decisions. This article presents a new knowledge development system (KDS) that should allow senior decision-makers and others to manage smarter and take their decision-making to the next level. A KDS represents the integration of information systems, and research and analysis, into one system. It can generate sophisticated, strategic information around complex issues, which should ultimately lead to wiser decisions. This article describes the KDS, provides an example of a current KDS and concludes by presenting a self-diagnostic tool for decision-makers to allow them to determine whether their organization could benefit from a KDS. PMID- 20357546 TI - Evaluation of the consensus-building process to develop a balanced scorecard for York Region public health. PMID- 20357547 TI - Adapting the Hamilton Health Sciences critical care pandemic triage protocol. PMID- 20357548 TI - Establishing an antimicrobial stewardship program. AB - Hospitals are faced with increasing challenges of antibiotic-resistant organisms and rising antimicrobial costs despite widespread attention to infection prevention and control measures. Government, professional organizations and accreditation bodies are all signalling an urgent need for the establishment of programs in hospitals to address antibiotic misuse. Although variations of such "antimicrobial stewardship programs" have been functioning in Canada for some time, a formal approach using change management and quality improvement principles has largely been lacking. We describe how we have established such a program in a teaching hospital, modelled on John Kotter's eight steps of leading change. PMID- 20357549 TI - 360-degree physician performance assessment. AB - Few jurisdictions have a robust common approach to assessing the quantitative and qualitative dimensions of physician performance. In this article, we examine the need for 360-degree physician performance assessment and review the literature supporting comprehensive physician assessment. An evidence-based, "best practice" approach to the development of a 360-degree physician performance assessment framework is presented, including an overview of a tool kit to support implementation. The focus of the framework is to support physician career planning and to enhance the quality of patient care. Finally, the legal considerations related to implementing 360-degree physician performance assessment are explored. PMID- 20357550 TI - Medical clearance in the psychiatric emergency setting: a call for more standardization. AB - Literature suggests little standardization in the practice of medical clearance of patients who present to emergency rooms in psychiatric crisis. The present quality improvement study examined current practice in a large psychiatric teaching hospital setting. Using chart review, the completeness of physical examination was examined for 10 body areas in a random sample of 20 psychiatric patients admitted via a psychiatric emergency department (ED) during a one-month period. Charts were examined for four professional groups - family physicians or nurse practitioners, psychiatry residents, medical students and general ED physicians. Results indicated a wide variation in documentation across the four groups and some body systems that were consistently never assessed. To improve standardization, a physical examination form is proposed that is user friendly and based on a review of current literature. PMID- 20357551 TI - Ombudsman in a mental health centre. AB - The Israeli Ministry of Health attributes significance to the issue of patients' complaints in mental health settings. A Public Petition Commission was established in Lev Hasharon Mental Health Center, Netanya, Israel, in 1997 and includes representatives from the medical, nursing and social work sectors. We examined the ombudsman's activities in Lev Hasharon Mental Health Center - as a representative institution for mental health centres - in an effort to characterize those who sought the services of the ombudsman and the treatment of the petitions. We also evaluated treatment of the complaint across time, the satisfaction of the complainant and the factors that influenced satisfaction. The files of those who sought the services of the ombudsman prior to and during the six-month duration of the study were examined using a predetermined checklist, and those who approached the ombudsman were contacted and asked whether or not they were satisfied with the treatment of their petition/complaint, and what factors influenced their level of satisfaction. Though solutions were found for only 55% of the problems, 88% of the patients reported satisfaction with the treatment of their petitions and complaints. Beyond the resolution of complaints, the office of the ombudsman improves dialogue with patients and their families, continuously improves in-patient care and perhaps reduces future complaints. PMID- 20357552 TI - Assessing innovations: what is the optimal approach for healthcare organizations? AB - Innovations in healthcare may improve patient outcomes and create economic benefits for healthcare organizations. The information available when an innovation is introduced to the market, however, may be insufficient to provide a compelling rationale for an institution to invest in the innovation. Generating the data required for an effective decision-making process involves assessing current performance indicators for an individual institution and the projected impact of adopting the innovation. The benefits of the innovation are verified after implementation. This article explores some of the issues and processes in evaluating healthcare innovations. PMID- 20357553 TI - Paying for technology. The cost of ignoring opportunity costs. PMID- 20357554 TI - Human resources in healthcare. AB - This issue of World Health & Population presents papers that have been published online by WHP and are selected here as representative of recent outstanding contributions to the journal. The papers in this issue include research from South and Southeast Asia, Africa and Latin America. PMID- 20357555 TI - The thai-Australian alliance: developing a rural health management curriculum by participatory action research. AB - In 2006, the Thai National Health Security Office and the Ministry of Public Health, through the Nakhonratchasima Provincial Health Office in Thailand, asked the Thai-Australian Health Alliance to identify competencies and skills for a health management curriculum for health professionals working in primary healthcare in rural Thailand. The study was conducted in Nakhonratchasima province, Thailand, utilizing questionnaires, focus group discussions and an intensive 3-day workshop involving a purposive sample of 35 participants drawn from various sectors in the health industry. Findings identified the core curriculum competencies and skills required by rural doctors, nurses and public health officers. Critical issues regarding continuing education for health professionals in primary healthcare were also examined. This study found that a primary healthcare approach should include the principles of sustainability and capacity building, and incorporate team-based, interprofessional and long-term continuous learning. PMID- 20357556 TI - "Social marketing" for early neonatal care: saving newborn lives in Pakistan. AB - According to the World Health Organization and the United Nations Children's Fund, developing countries carry a large share of neonatal mortality in the world. According to UNICEF, almost 450 newborn children die every hour, mostly from preventable causes. Restricted access to quality and hygienic delivery services and limited knowledge about handling the newborn aggravate the situation. South Asia, and Pakistan in particular, have reduced their child and infant mortality during the last decade; however, neonatal mortality still remains unacceptably high. There are multiple reasons, mainly related to practices and behaviours of communities and traditional birth attendants. Rural and poor populations suffer most in Pakistan, where three out of five deliveries still occur at home. Traditional community practices and conservative norms drastically affect neonatal health outcomes. Preventing sepsis at the umbilical cord, keeping the baby at the correct temperature after birth and early initiation of exclusive breastfeeding are three simple strategies or messages that need to be disseminated widely to prevent many neonatal mortalities and morbidities. Since inappropriate practices in handling newborns are directly linked with persistent and unremitting behaviours among health providers and the community at large, we suggest doing robust "social marketing" for saving newborn lives. The objective of the paper is to present a social-marketing strategy and a marketing mix that will help address and surmount actual barriers and promote alternative behaviours in early neonatal care. PMID- 20357557 TI - Determinants of gender differences in health among the elderly in Latin America. AB - This paper identifies the main gender differences in health and socio-economic characteristics of the elderly in four Latin American cities. Using locally weighted regressions as well as a flexible model specification that treats age non-parametrically, we investigate whether these unadjusted gender gaps in health are due to gender differences in the distribution of age and other explanatory variables. Interestingly, for all cities, the analyses show a gender gap in health in favour of males at each age. The gaps are larger when one uses functional impairment in mobility and personal self-care as indicators of an individual's health instead of self-reported health. Furthermore, controlling for demographic characteristics, baseline health and the availability of family support do little to change the disadvantage for women in measured health outcomes. Controlling for socio-economic variables does, however, reduce most of the gender differences in health. PMID- 20357558 TI - The potential for nosocomial infection transmission by white coats used by physicians in Nigeria: implications for improved patient-safety initiatives. AB - Microbiological analysis of swabs taken from the cuffs and pocket mouths of physicians' white coats in an acute care hospital showed that 91.3% of the coats had bacterial contamination. Specifically diphtheroids, Staphylococcus aureus and Gram-negative bacilli were isolated. In contrast, comparatively lower rates of bacterial contamination were observed on the white coats (1) of visiting physicians, (2) of the medical unit compared with the rest of the hospital, (3) that were less 1 year old, and (4) that were laundered daily. Further, the white coats of physicians who wore them only when seeing patients had significantly lower bacterial contamination than white coats of physicians who wore theirs during clinical and nonclinical duties (chi(2) = 4.99, df = 1, p < .05). In particular, white-coat cuffs had a higher bacterial load than the mouths of the pockets. The bacterial isolates were resistant to nearly all of the antibiotics tested; the most effective, however, was ciproflox. Results suggest that physicians' white coats may increase nosocomial infection transmission. Proper handling of white coats by physicians and other healthcare workers could minimize cross-contamination and improve patient safety by potentially reducing nosocomial infections. PMID- 20357559 TI - Safe abortion services in Nepal: initial years of availability and utilization. AB - INTRODUCTION: Following the liberalization of the very strict Nepalese abortion law in 2002, the first services for safe induced abortion were introduced in 2004 at the nation's largest women's hospital. This paper examines the client profile, the context of demand for services, affordability and satisfaction with services. DATA AND METHODS: Data for the analysis came from a survey of women who presented themselves at the hospital for induced abortion services and subsequently received the services. RESULTS: Based on a survey of 672 clients, the median age was 26, and most women were married with an average of two living children. The majority reported being impregnated by the husband. Nearly three out of five gave their primary reason for termination as already having the number of children desired; another 42% cited finances. About two-thirds made the decision to abort jointly with the male partner. Most were satisfied with the services received and expenses incurred. About two-fifths reported having used a modern contraceptive method at the time the unwanted pregnancy occurred, while 22.6% reported practising either the safe-period or withdrawal methods. CONCLUSION: The clinic has provided affordable, quality abortion services to women in need. Findings also suggest that many areas need services strengthened, including the continued role of the family planning program in preventing unintended pregnancies. PMID- 20357563 TI - Gailey's 1895 anesthetic inhaler. PMID- 20357564 TI - Churchill acupuncture needles. PMID- 20357565 TI - Temporal trends in the epidemiology of severe postoperative sepsis after elective surgery: a large, nationwide sample. AB - INTRODUCTION: Multiple studies have used administrative datasets to examine the epidemiology of sepsis in general, but the entity of postoperative sepsis has been studied less intensively. Therefore, we undertook an analysis of the epidemiology of postoperative sepsis using the Nationwide Inpatient Sample, the largest in-patient dataset available in the United States. METHODS: Elective admissions of patients aged 18 yr or older with a length of stay more than 3 days for any 1 of the 20 most common elective operative procedures were extracted from the dataset for the years 1997-2006. Postoperative sepsis was defined using the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes; severe sepsis was defined as sepsis along with organ dysfunction. Logistic regression was used to assess the significance of temporal trends after adjusting for relevant demographic characteristics, operative procedure, and comorbid conditions. RESULTS: We identified 2,039,776 admissions for analysis. The rate of severe sepsis increased from 0.3% in 1997 to 0.9% in 2006. This trend persisted after adjusting for relevant covariables-the adjusted odds ratio of severe sepsis per year increase in the study period was 1.12 (95% CI, 1.11-1.13; P < 0.001). The in-hospital mortality rate for patients with severe postoperative sepsis declined from 44.4% in 1997 to 34.0% in 2006; this trend also persisted after adjustment for relevant covariables-the adjusted odds ratio per year was 0.94 (95% CI, 0.93-0.95; P < 0.001). CONCLUSION: During the 10 yr period that we studied, there was a marked increase in the rate of severe postoperative sepsis but a concomitant decrease in the in-hospital mortality rate in severe sepsis. PMID- 20357566 TI - Corning's "ice-water cap" for congestive headaches. PMID- 20357569 TI - Early labor neuraxial analgesia: effects on the progress and outcome of labor. PMID- 20357571 TI - Rapid eye movement sleep and general anesthesia. PMID- 20357573 TI - Sensory nerve damage after the use of the LMA supreme. PMID- 20357579 TI - Current world literature. PMID- 20357584 TI - Communication between the doctor and the child. PMID- 20357585 TI - Functional results after surgical treatment for congenital knee dislocation. AB - BACKGROUND: Congenital knee dislocation (CDK) is a rare congenital deformity, which often requires surgery for treatment. Little objective data exist characterizing the outcome of patients who require operative treatment for this condition. The purposes of this study were to objectively evaluate the functional, clinical, and gait outcomes of patients who underwent surgical treatment of CDK; and compare the results of outcome between 2 surgical approaches for this condition: quadricepsplasty and femoral shortening. METHODS: We performed a retrospective review of all patients (7) treated surgically for CDK. Patients were evaluated at an average follow-up of 12+6 years. Each patient underwent a clinical examination, functional evaluation using the Lysholm Knee Questionnaire and Pediatric Outcomes Data Collection Instrument, and a 3 dimensional gait evaluation. The results of the total group were compared with normal controls. Additionally, results of the patients treated with quadricepsplasty were compared with patients treated with femoral shortening. RESULTS: Total knee range of motion for the entire group averaged 112 degrees, with 8 of the 9 knees having flexion>90 degrees. Seven of the 9 knees were found to have some degree of instability on examination, yet none of the patients reported using any form of brace for ambulation. Functional evaluation showed good knee specific and overall function, comparable to normal controls. There were no differences in clinical or functional outcomes between the 2 surgical approaches. Gait analysis revealed a stiff-knee gait pattern to the congenital knee dislocation group, as compared with normal controls, and subtle differences in knee function between the surgical approaches. CONCLUSIONS: The function of patients after surgical treatment for CDK seems to be quite good compared with normal controls. Good knee specific and overall function scores are reported with limitations seen only in higher demand activities. Despite instability of the knee noticed on clinical examination, patients ambulate without braces and have a functional knee range of motion. Little difference in outcome was seen between the 2 surgical approaches used to treat this condition. LEVEL OF EVIDENCE: Therapeutic Study, Level III. PMID- 20357586 TI - Medial collateral ligament of the knee on magnetic resonance imaging: does the site of the femoral origin change at different patient ages in children and young adults? AB - BACKGROUND: The medial patellofemoral ligament (MPFL), a chief medial restraint preventing lateral patellar dislocation, often is reconstructed in children with recurrent dislocation. The femoral MPFL attachment can be difficult to delineate at surgery. Therefore, the origin of the medial collateral ligament (MCL) frequently is used to approximate the reattachment site. The purpose of our study was to compile normative data from MR imaging examinations over different patient ages, to determine the effect of growth on the relationship of the MCL origin site to the distal femoral physis and medial femoral condyle (MFC). SUBJECTS AND METHODS: This HIPAA-compliant study was IRB approved. Informed consent requirement was waived. Three hundred knee MR imaging examinations (143 boys, 157 girls, 0-20 y) were evaluated. MCL origin to femoral physis distance, MFC height, and MCL origin-physis distance: MFC height ratio (MCL:MFC ratio) were calculated. Relationships between these values and age, gender, and physeal patency were assessed using linear regression models. RESULTS: With physeal patency, MCL origin-physis distance was significantly associated with increasing age in boys (P=0.0394), and trended toward significance in girls (P=0.0557). Distance increased 0.01 cm/y in both genders. MFC height increased 0.15 cm/y in boys and 0.13 cm/y in girls (P<0.0001). MCL:MFC ratio decreased 0.01/y (P<0.0001). With physeal closure, no significant change was measured for any variable. CONCLUSIONS: During growth, there are statistically significant, albeit minimal, changes of the MCL origin-physis distance and MFC height. As these changes are essentially negligible, no adjustment for age is needed during restorative MPFL surgery in growing children. CLINICAL RELEVANCE: As there is neglible change in location of the origin of the MCL relative to the distal femoral physis during skeletal growth in both boys and girls, no adjustment for patient age is necessary when using the origin of the MCL as a landmark to locate the site of femoral reattachment of a disrupted MPFL. PMID- 20357587 TI - Evaluation of embryonic and perinatal myosin gene mutations and the etiology of congenital idiopathic clubfoot. AB - BACKGROUND: Congenital idiopathic clubfoot is the most common musculoskeletal birth defect that develops during the fetal period, but with no known etiology. MYH 2, 3, 7, and 8 are expressed embryonically or perinatally, the period during which congenital idiopathic clubfoot develops; are all components of Type II muscle, which is consistently decreased in clubfoot patients; and are associated with several muscle contracture syndromes that have associated clubfoot deformities. In this study, we hypothesized that a mutation in an embryonic or perinatal myosin gene could be associated with congenital idiopathic clubfoot. METHODS: We screened the exons, splice sites, and predicted promoters of 24 bilateral congenital idiopathic clubfoot patients and 24 matched controls in MYH 1, 2, 3, and 8 via sequence-based analysis, and screened an additional 76 patients in each discovered SNP. RESULTS: Although many single-nucleotide polymorphisms were found; none proved to be significantly associated with the phenotype of congenital idiopathic clubfoot. Also, no known mutations that cause distal arthrogryposis syndromes were found in the congenital idiopathic clubfoot patients. CONCLUSIONS: These findings demonstrate that congenital idiopathic clubfoot has a different pathophysiology than the clubfoot seen in distal arthrogryposis syndromes, and defects in myosin are most likely not directly responsible for the development of congenital clubfoot. Given the complexity of early myogenesis, many regulatory candidate genes remain that could cause defects in the hypaxial musculature that is invariably observed in congenital idiopathic clubfoot. CLINICAL RELEVANCE: This study further differentiates congenital idiopathic clubfoot as distinct from other complex genetic syndromes that can present with similar deformities, and thus facilitates further research to improve the clinical diagnosis and treatment of congenital idiopathic clubfoot. PMID- 20357588 TI - Gait analysis of children treated for moderate clubfoot with physical therapy versus the Ponseti cast technique. AB - BACKGROUND: Nonoperative methods for clubfoot treatment include the Ponseti technique and French functional method. The purpose of this study was to compare the gait of children presenting with moderate clubfeet who were treated successfully with these techniques. We hypothesized: (1) no difference in gait parameters of moderate clubfeet treated with either of these nonsurgical techniques and (2) gait parameters after treatment for less severe feet would more closely approximate normal gait. METHODS: Patients whose clubfeet were initially scored between 6 and <10 on the Dimeglio scale underwent gait analysis at the age of 2 years. Kinematic evaluation of the ankle was analyzed and kinematic data were classified as abnormal if more than 1 standard deviation from age-matched normal data. Spearman nonparametric correlation coefficients were used to analyze combined data of moderate to very severe clubfeet to determine any relationship between initial severity and gait outcomes. RESULTS: Gait analysis was performed on 33 patients with 40 moderate clubfeet [17 Ponseti, 23 French physical therapy (PT) feet]. Three Ponseti feet were excluded because they had undergone surgery. No statistically significant differences existed in ankle equinus, dorsiflexion, or push-off plantarflexion between the groups. Swing phase foot drop was present in 6 PT feet (26%) compared with zero Ponseti feet (P=0.026). Normal kinematic ankle motion was present more often in the Ponseti group (82%) than PT (48%) (P=0.027). Regardless of treatment, residual intoeing was seen in one-third of children with moderate clubfeet. The combined group of moderate and severe clubfeet showed no correlation between initial Dimeglio score and presence of normal ankle motion or normal gait at 2 years-of-age. CONCLUSIONS: Normal ankle motion was documented more frequently in the Ponseti feet compared with the PT group. Recent implementation of early tendo-achilles release in PT feet may change these outcomes in the future. In conclusion, gait in children with moderate clubfeet is similar to those in patients with severe clubfeet, but the likelihood of surgery may be less. LEVEL OF EVIDENCE: Therapeutic level II. PMID- 20357589 TI - Development of calcaneal gait without prior triceps surae lengthening: an examination of predictive factors. AB - BACKGROUND: Although equinus is more common in cerebral palsy (CP), the prevalence of calcaneal gait (CG) has been reported at more than 30% among patients with CP, even in the absence of prior surgical intervention. The goal of this study was to identify patient characteristics predictive of the development of CG in patients without prior triceps surae lengthening. METHODS: Gait data were reviewed for 58 participants with bilateral involvement owing to CP (116 limbs) who had 2 gait analysis tests with no triceps surae lengthening between tests. None of the patients exhibited CG at the initial gait study. Patients were grouped according to whether or not they exhibited CG patterns at the second test. Factors potentially predictive of calcaneal gait patterns were compared statistically between groups. RESULTS: CG was shown by 24/116 extremities (21%) at the second study. The CG group experienced greater increase in body weight and body mass index between tests (P=0.006 and 0.03 respectively). Passive dorsiflexion range with the knee flexed was significantly greater in the CG group (P=0.008). The CG group also showed a tendency toward greater plantarflexor weakness, although this only approached statistical significance (P=0.08) likely owing to small sample size. Age, CP subtype, time to follow-up, hamstring range, selective motor control, and gross motor functional level were not predictive. CONCLUSIONS: Patients who undergo (or have potential to undergo) significant weight gain, and have tendencies toward excessive passive dorsiflexion with the knee flexed may be at risk for development of CG over time. In such patients, treatment regimens should include therapy to maintain or improve plantarflexor strength, and methods to prevent overstretching the plantarflexors. Nonsurgical treatments for triceps surae contractures, such as serial casting, may be preferable, to avoid hastening development of calcaneal crouch gait over time. LEVEL OF EVIDENCE: Prognostic study---Level III (case-control). PMID- 20357590 TI - Access to care for children with fractures. AB - BACKGROUND: Earlier studies have found that children with fractures and PPO insurance have no access problems to orthopaedic care, but children with Medicaid have problems with access to orthopaedic care. METHODS: Fifty randomly selected orthopaedic offices in each of the 2 counties served by a children's hospital were telephoned to seek an appointment for a fictitious 10-year-old boy with a forearm fracture. Each office was called twice, 1 time reporting that the child had PPO insurance and 1 time that he was having Medicaid. In the second arm of the study, data including insurance status were prospectively collected on all patients with fractures seen in the emergency department of children's hospital. RESULTS: Of the 100 offices telephoned, 8 offices gave an appointment within 1 week to the child with Medicaid insurance. Thirty-six of the 100 offices gave an appointment within 1 week to the child with PPO insurance. For the 2210 pediatric fractures seen in the emergency department, the payer mix for patients presenting initially to our facility (1326 patients) was 41% Medicaid, 9% selfpay, and 50% commercial. For the patients presenting to our emergency department after being seen at an outside facility first (884 patients), the payer mix was 47% Medicaid, 13% self-pay, and 40% commercial. The percentages between these two groups were similar but did have a statistically significant difference (P=0.021). CONCLUSIONS: To the best of our knowledge, this is the first study that reports a majority (64/100) of orthopaedic offices in the region would not care for a child with a fracture regardless of insurance status. Consistent with earlier studies, children with Medicaid have less access to care. The similar insurance status of children sent to the emergency department from other facilities compared with those presenting directly suggests that children in this study are sent to a children's hospital for specialized care rather than for economic reasons. LEVEL OF EVIDENCE: Level II. PMID- 20357591 TI - Emergency room visits by pediatric fracture patients treated with cast immobilization. AB - BACKGROUND: The purpose of this review was to determine when and why pediatric patients with cast complaints return to the emergency room (ER). If this could be determined, educational and treatment strategies may help decrease the number of these visits and the cost of care. METHODS: Retrospective chart review of patients initially seen in a busy urban pediatric orthopaedic clinic identified those who had an ER visit because of a cast-related problem over a 5-year period. Patients were included only if they were seen for their initial visit and cast application in our fracture clinic. RESULTS: Of 168 ER visits made by 155 children treated with cast immobilization, 29% were because of a wet cast; 10%, a damaged cast; 23%, a tight cast; 13%, a loose cast; and 10%, pain. In addition to wet and damaged casts, compliance issues included a missed clinic appointment (5%) and being told by medical personnel to return to the ER for a cast check (8%). Several groups with a high risk for return to the ER were identified: the younger the patient, the more likely that the cast was too loose or wet, and the older the patient, the more likely the cast was too tight. Cast type also played a role: a significantly higher rate of return to the ER was found with long arm, long leg, and hand casts. There were no major complications and no child required hospitalization. CONCLUSIONS: All 168 ER visits required only a cast change or reassurance, which could have been done during regular fracture clinic hours; no child required hospitalization or surgery. From these results, a program has been instituted that includes patient education, triage, and follow-up in our fracture clinics to not only improve the quality of patient care but to decrease the financial burden on physicians and the healthcare system. LEVEL OF EVIDENCE: Economic and decision analysis, Level III. PMID- 20357592 TI - Nerve injuries associated with pediatric supracondylar humeral fractures: a meta analysis. AB - BACKGROUND: Supracondylar fractures of the humerus are the most common type of elbow fracture in children. Of all complications associated with supracondylar fractures, nerve injury ranks highest, although reports of the incidence of specific neurapraxia vary. This meta-analysis aims primarily to determine the risk of traumatic neurapraxia in extension-type supracondylar fractures as compared with that of flexion-type fractures; secondarily it aims to use subgroup analysis to assess the risk of iatrogenic neurapraxia induced by pin fixation. METHODS: A literature search identified studies that reported the incidence of nerve injury presenting with displaced supracondylar fractures of the humerus in children. Meta-analysis was subsequently performed to evaluate the risk of traumatic neurapraxia associated with supracondylar fractures. Subgroup analysis of included articles was additionally performed to assess the risk of iatrogenic neurapraxia associated with lateral-only or medial/lateral pin fixation. RESULTS: Data from 5148 patients with 5154 fractures were pooled for meta-analysis. Among these patients, traumatic neurapraxia occurred at a weighted event rate of 11.3%. Anterior interosseous nerve injury predominated in extension-type fractures, representing 34.1% of associated neurapraxias; meanwhile, ulnar neuropathy occurred most frequently in flexion-type injuries, representing 91.3% of associated neurapraxias. Nerve injury induced by lateral-only pinning occurred at a weighted event rate of 3.4%, while the introduction of a medial pin elicited neurapraxia at a weighted event rate of 4.1%. Lateral pinning carried increased risk of median neuropathy, whereas the use of a medial pin significantly increased the risk of ulnar nerve injury. CONCLUSIONS: Of nerve injury associated with extension-type fractures, anterior interosseous neurapraxia ranks highest, whereas of flexion-type neuropathy, ulnar nerve injury predominates. We confirm that medial pinning carries the greater overall risk of nerve injury as compared with lateral-only pinning and that the ulnar nerve is at risk of injury in medially pinned patients. We additionally suggest that lateral pinning carries neurapraxic risk with respect to the median nerve. LEVEL OF EVIDENCE: Level IV; Meta-analysis. PMID- 20357593 TI - Growing rods for spinal deformity: characterizing consensus and variation in current use. AB - SUMMARY OF BACKGROUND DATA: Growing rods are a commonly used form of growth guidance for patients with early onset scoliosis, but no studies exist to characterize their use among a large group of surgeons. METHODS: A survey regarding growing rod use preferences and a case-based survey regarding early onset scoliosis were completed by an international group of surgeons. Two hundred and sixty-five growing rod patients treated over 4.7+/-2.1 years in the Growing Spine Study Group database were analyzed to characterize actual practice and compare it with the survey results. All patients had at least 2 years of treatment. RESULTS: In the case-based survey, there was correlation (P=0.04, r=0.58) between increasing curve size and choice of growing rods over nonoperative treatment, rib-based distraction (vertically expandable prosthetic titanium rib), growth guidance (Shilla), and primary fusion. In practice, growing rods were used for most types of early onset spine deformity. Most surgeons stated that their indication for growing rod treatment was a curve over 60 degrees (10/13) in a patient younger than 8 to 10 years (14/17). In practice, mean curve at rod insertion was 73+/-20 degrees and age was 6.0+/-2.5 years. Other factors favoring growing rods included curve rigidity (8/17), brace intolerance (6/17) and syndromic diagnoses (2/17). In the database, idiopathic scoliosis represented <50% of diagnoses. The most common preferred surgical lengthening interval was 6 months. However, in practice, lengthening actually occurred at a mean of 8.6+/-5.1 months. In the database, the number of growing rod insertions per year (P=0.02, r=0.96) and percentage of surgeons using dual rods over single rods (P=0.065, r=0.93) increased over time. Insertion age (P=0.075, r=-0.87) and lengthening interval (P=0.006, r=-0.69) decreased as time progressed. The most common stated indication on the survey for final fusion was skeletal maturity (13/17), and 7/13 surgeons used Risser 3 or more. Indications to stop lengthening included complications such as infection or implant failure (14/17), curves progressing past 90 degrees (8/17), and failure to distract (6/13). The most common method of final fusion was replacement of implants with more intermediate anchors. CONCLUSIONS: Significant practice variation exists in growing rod treatment, but there is some consensus on indications for surgery including curve size, diagnosis and age, and lengthening intervals and final fusion methods. Mean curve size and lengthening interval are greater in practice than in surgeons' stated aims. In principle and in practice, most growing rods are used for curves over 60 degrees in patients under 10, in all diagnoses. This information may form a starting point as practice variation is studied. PMID- 20357594 TI - Surgical treatment of kyphosis in children in healed stages of spinal tuberculosis. AB - BACKGROUND: Very less literature focuses on the treatment of kyphosis in healed stages of spinal tuberculosis (TB), especially in children. The purpose of this study was to evaluate the outcomes of anterior release, decompression, deformity correction, and instrumented fusion, followed by posterior osteotomy, deformity correction, and pedicle screw instrumented fusion, which is used to treat kyphosis in children in healed stages of spinal TB. METHODS: Sixteen children with kyphotic deformity of the spine in healed stages of TB underwent anterior release, decompression, deformity correction, and instrumented fusion, followed by posterior osteotomy, deformity correction, and pedicle screw instrumented fusion between 2003 and 2007 with at least 2 years of follow-up. Radiologic assessment including the angle of kyphosis and scoliosis, and neurologic status using the modified Frankel grade were analyzed before surgery, after surgery, and at the last follow-up. Fusion was evaluated on flexion-extension lateral radiographs. RESULTS: Good cosmetic results were achieved in all patients. Neurologic improvement was shown in all 4 patients with paraplegia. The mean preoperative angle of kyphosis was 55.8 degrees that reduced to 21.7 degrees, postoperatively. The difference in the mean angle of kyphosis was statistically significant (P<0.05). The mean angle of kyphosis at the last follow-up was 23.2 degrees. The mean correction loss was 1.5 degree, and there was no statistically significant difference in the mean angles of kyphosis between the postoperative and last follow-up measurements. The mean preoperative angle of scoliosis was 6.9 degrees that reduced to 0.8 degree postoperatively. The difference in the mean angle of scoliosis was statistically significant (P<0.05). The mean angle of scoliosis at the last follow-up was 0.9 degree. The mean correction loss was 0.2 degree and there was no statistically significant difference in the mean angles of scoliosis between the postoperative and last follow-up measurements. All patients returning for follow-up had bony fusion. There were no cases of failure of fixation. CONCLUSIONS: Combined anterior and posterior osteotomy, deformity correction, and instrumented fusion halted progression of kyphosis and improved neurologic symptoms. LEVEL OF EVIDENCE: Therapeutic-level IV, retrospective study. PMID- 20357595 TI - The mechanism of acute elbow flexion contracture in children with congenital proximal radioulnar synostosis. AB - We have evaluated and treated 3 cases of acute onset elbow flexion contracture in children ranging in age from 6 to 13 years, with type-IV (Cleary and Omer) congenital proximal radioulnar synostosis. All were resolved by manipulative traction under general anesthesia during which an audible elbow "snap" was noted. Two of the cases required surgical treatment of a deformed radial head with good results after a 2 to 4-year follow-up. Our clinical radiographic and intraoperative evidence suggests that the acute onset fixed-flexion contracture results from an anterosuperiorly overgrown dislocated radial head becoming trapped under hypertrophied annular ligament-type tissue after elbow hyperflexion. Excision of the dislocated radial head after release from its entrapment was effective in 2 of the 3 patients in this report, and should be considered. PMID- 20357596 TI - Steel syndrome: dislocated hips and radial heads, carpal coalition, scoliosis, short stature, and characteristic facial features. AB - BACKGROUND: A syndrome of children with short stature, bilateral hip dislocations, radial head dislocations, carpal coalitions, scoliosis, and cavus feet in Puerto Rican children, was reported by Steel et al in 1993. The syndrome was described as a unique entity with dismal results after conventional treatment of dislocated hips. The purpose of this study is to reevaluate this patient population with a longer follow-up and delineate the clinical and radiologic features, treatment outcomes, and the genetic characteristics. METHODS: This is a retrospective cohort study of 32 patients in whom we evaluated the clinical, imaging data, and genetic characteristics. We compare the findings and quality of life in patients with this syndrome who have had attempts at reduction of the hips versus those who did not have the treatment. RESULTS: Congenital hip dislocations were present in 100% of the patients. There was no attempt at reduction in 39% (25/64) of the hips. In the remaining 61% (39/64), the hips were treated with a variety of modalities fraught with complications. Of those treated, 85% (33/39) remain dislocated, the rest of the hips continue subluxated with acetabular dysplasia and pain. The group of hips that were not treated reported fewer complaints and limitation in daily activities compared with the hips that had attempts at reduction. CONCLUSIONS: Steel syndrome is a distinct clinical entity characterized by short stature, bilateral hip and radial head dislocation, carpal coalition, scoliosis, cavus feet, and characteristic facial features with dismal results for attempts at reduction of the hips. LEVEL OF EVIDENCE: Prognostic Study Level II. PMID- 20357597 TI - Orthopaedic manifestations of Navajo familial neurogenic arthropathy. AB - BACKGROUND: Navajo Familial Neurogenic Arthropathy is a disease identified in Navajo children, primarily residing in Arizona, New Mexico, and Utah. To date, there are no reports in the orthopaedic literature regarding this disorder, particularly the clinical manifestations and treatment considerations. METHODS: We carried out a retrospective chart and radiographic review of 2 patients with Navajo familial neurogenic arthropathy. We present these 2 patients as representative of the orthopaedic manifestations of Navajo familial neurogenic arthropathy. RESULTS: Both patients have significant axial and appendicular bone abnormalities, Charcot-type arthopathy, heat intolerance and also anhidrosis. They have normal intelligence. Both patients underwent surgical interventions, with recurrent deformity and infection being the most common complications. CONCLUSIONS: Navajo familial neurogenic arthropathy is a rare clinical entity, seen most commonly in the southwestern regions of the United States. Patients are found to have a myriad of orthopaedic abnormalities, and surgical intervention, while sometimes indicated, can be fraught with complications. LEVEL OF EVIDENCE: Level IV, case series. PMID- 20357598 TI - Teleconsultation using multimedia messaging service for management plan in pediatric orthopaedics: a pilot study. AB - BACKGROUND: Application and assessment of the usefulness of image transfer through a mobile telephone in pediatric orthopaedic practice was investigated. METHODS: Twenty patients with traumatic lesions requiring urgent consultation were included. Relevant x-rays were photographed and transferred using Multimedia Messaging Service to the orthopaedic surgeon at our department. The discussion on the need to transfer the patient for treatment and the final treatment was retrospectively scrutinized by 10 independent orthopaedic surgeons. The agreement on the diagnosis and the management plan proposed after image transfer were assessed. RESULTS: The lesion concerned the lower limb in 6 cases, upper limbs in 13 cases, and the spine in 1 case in patients aged 2 to 16 years. The transmitted images were 160 x 120-pixel jpeg files in 1 case, 240 x 180-pixel jpeg files in 8 cases, 320 x 240-pixel jpeg files in 1 case, and 640 x 480-pixel jpeg files in 10 cases. In all the cases studied, all the investigators agreed that the images were good enough for doing the diagnosis even in cases of minor or nondisplaced fractures. The same decisions of transfer or management were taken in all the cases by all the investigators. Review of the transferred images versus the original full-scale images did not change the final diagnosis and management plan. CONCLUSIONS: In this study, even in case of low-resolution images (160 x 120-pixel jpeg), images were of sufficiently high quality for interpretation. This enables rational management decisions to be made using this costless and widely available technology. In patients requiring surgical treatment, a final operative decision is mandatory after transfer, bedside examination, and review of other data in addition to images. Teleconsultation using Multimedia Messaging Service is especially useful to improve remote management of orthopaedic patients in local hospitals or for decisions of transfer when surgical treatment is needed. CLINICAL RELEVANCE: Level IV (case series). PMID- 20357599 TI - Kingella kingae osteoarticular infections in young children: clinical features and contribution of a new specific real-time PCR assay to the diagnosis. AB - BACKGROUND: Kingella kingae is an emerging pathogen that may be recognized as the most common bacteria responsible for osteoarticular infections (OAI) in young children. However, its diagnosis remains a challenge and thus little evoked in infants, because K. kingae is a difficult germ to isolate on solid medium, and clinical signs are often mild. The main objective of this prospective study is to describe the clinical, biologic, and radiologic features of children with OAI caused by K. kingae. In addition, we describe the usage of a new specific real time PCR assay in children under 4 years admitted for OAI with a probe that detects 2 independent gene targets from the K. kingae RTX toxin. PATIENTS AND METHODS: All children less than 4 years admitted in our institution between January 2007 and November 2009 for suspected OAI were enrolled in this prospective study (43 cases). Age, gender, clinical signs, duration of symptoms, bone or joint involved, imaging studies, and laboratory data, including bacterial investigations, full blood count, erythrocyte sedimentation rate, and serum C reactive protein were collected for analysis. RESULTS: Identification of the microorganism was possible for 28 cases (65.1%) yielding K. kingae in 23 cases (82.1%). Mean age of children with K. kingae OAI was 19.6 months. Less than 15% of these patients were febrile during the admission, but 46% of them presented a history of fever-peak superior to 38.5 degrees C before admission. Thirty-nine percent of the children with K. kingae OAI had normal C-reactive protein; WBC was elevated in only 2 cases, whereas 21 patients had abnormal erythrocyte sedimentation rate, and 13 abnormal platelet counts. Direct Gram staining and classical isolation methods were negative for all cases subsequently detected as K. kingae OAI by specific real-time PCR. CONCLUSION: This study confirms that K. kingae is the major bacterial cause of OAI in children less than 4 years. The real-time PCR assay, specific to the K. kingae RTX toxin, provides interesting diagnostic performance when implemented in the routine microbiologic laboratory. Needless to say, a bigger cohort is required to adequately study this new qPCR assay, but the results so far seem promising. The most important additional finding is the mild-to-moderate clinical, radiologic, and biologic inflammatory response to K. kingae infection with the result that these children present few criteria evocative of OAI. LEVEL OF EVIDENCE: II. PMID- 20357600 TI - Cancer control planners' perceptions and use of evidence-based programs. AB - The Cancer Prevention and Control Research Network surveyed 282 cancer control planners to inform its efforts to increase the use of evidence-based cancer control programs (EBPs; programs that have been scientifically tested and have successfully changed behavior). Respondents included planners from organizations in state Comprehensive Cancer Control coalitions as well as other governmental and nongovernmental organizations and community-based coalitions. Respondents provided information about personal and organizational characteristics, their cancer control programs, their attitudes toward EBPs, and their awareness and use of Web-based resources for EBPs. Although findings showed strong preferences for cancer control programs that have been shown to work, less than half of respondents (48%) had ever used EBP resources. Regardless of whether they had used EBP resources, almost all respondents (97%) indicated that further training would help them and their organizations adopt and adapt EBPs for use in their communities. The most frequently endorsed training needs were finding and securing additional resources (such as funding and technical assistance), followed by adapting EBPs for cultural appropriateness. The Cancer Prevention and Control Research Network consortium is using these findings to develop a Web based interactive training and decision support tool that is responsive to the needs identified by the survey respondents. PMID- 20357601 TI - Crosswalking public health and health education competencies: implications for professional preparation and practice. AB - This article highlights similarities and differences between the public health competencies recently developed by the Association of Schools of Public Health (ASPH) and one public health specialty, health education (HE), which has used competencies in its quality assurance systems for more than 20 years. Based on a crosswalk methodology developed for this analysis, some 50 percent to 61 percent of the HE and ASPH competencies had similarities of varying degrees; 18 percent were deemed matches due to sameness in skill or content. Most similarities were found between the ASPH social and behavioral sciences competencies and the HE competencies. Significant domains of "no match" were found between the HE and ASPH competencies in the areas of Systems Thinking, Leadership, and Public Health Biology. The study results have implications for academic programs related to curricula review and revision, continuing education providers who are developing training agendas for the workforce, employers anticipating competencies in new job hires, and prospective students and practitioners who are considering a form of certification. Qualitative insights from the study related to professional culture, purpose, age, and consistency of the scope or depth of the two competency sets, as well as the crosswalk methodology itself, may be useful to those comparing other competency sets. PMID- 20357602 TI - Translating public health knowledge into practice: development of a lay health advisor perinatal tobacco cessation program. AB - The value of lay health advisor (LHA) interventions as an effective approach toward ameliorating racial, ethnic and/socioeconomic health disparities has been noted by researchers and policy makers. Translating scientific knowledge to bring state-of-the-art health promotion/disease prevention innovation to underserved populations is critical for addressing these health disparities. This article examines the experiences of a community-academic partnership in designing, developing, and implementing an evidence-based, LHA-driven perinatal tobacco cessation program for low-income, predominately African American and Hispanic women. A multimethod process evaluation was conducted to analyze three essential domains of program implementation: (1) fit of the tobacco cessation program into the broader project context, (2) feasibility of program implementation, and (3) fidelity to program implementation protocols. Findings indicate that project partners have largely succeeded in integrating an evidence-based tobacco cessation program into a community-based maternal and infant health project. The successful implementation of this intervention appears to be attributable to the following two predominant factors: (1) the utilization of a scientifically validated tobacco cessation intervention model and (2) the emphasis on continuous LHA training and capacity development. PMID- 20357603 TI - Indoor anthrax decontamination: how clean is clean? PMID- 20357605 TI - Lessons learned from the investigation of a cluster of cutaneous anthrax cases in Connecticut. AB - In 2007, two cases of cutaneous anthrax associated with West African drum making were reported in Connecticut in a drum-maker and his child. Although both cases were due to exposure to naturally occurring Bacillus anthracis from imported animal hides, ensuing investigative and remediation efforts were affected by the intentional B anthracis attacks in 2001. To share our experience of responding to an outbreak of anthrax in the biologic terrorism preparedness era, we summarize Connecticut's investigation and describe lessons learned. Laboratory capacity to rapidly assist in diagnosing anthrax, collaborative associations between epidemiologists and law enforcement personnel, and training in use of the Incident Command System, all these a result of public health preparedness, enhanced the initial recognition and subsequent investigation of these anthrax cases. However, without established guidelines for environmental risk assessment and remediation of private residences contaminated by B anthracis, challenges were encountered that resulted in a conservative and expensive approach to remediation. Without a more rigorous approach to ensuring that B anthracis spore free hides are used, the making of animal hide drums is likely to pose a continuing risk for anthrax to those working with contaminated hides and those exposed to subsequently contaminated environments. PMID- 20357606 TI - Public health errors: costing lives, millions at a time. PMID- 20357604 TI - Public health and environmental response to the first case of naturally acquired inhalational anthrax in the United States in 30 years: infection of a new york city resident who worked with dried animal hides. AB - In Pennsylvania on February 16, 2006, a New York City resident collapsed with rigors and was hospitalized. On February 21, the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene were notified that Bacillus anthracis had been identified in the patient's blood. Although the patient's history of working with dried animal hides to make African drums indicated the likelihood of a natural exposure to aerosolized anthrax spores, bioterrorism had to be ruled out first. Ultimately, this case proved to be the first case of naturally occurring inhalational anthrax in 30 years. This article describes the epidemiologic and environmental investigation to identify other cases and persons at risk and to determine the source of exposure and scope of contamination. Because stricter regulation of the importation of animal hides from areas where anthrax is enzootic is difficult, public healthcare officials should consider the possibility of future naturally occurring anthrax cases caused by contaminated hides. Federal protocols are needed to assist in the local response, which should be tempered by our growing understanding of the epidemiology of naturally acquired anthrax. These protocols should include recommended methods for reliable and efficient environmental sample collection and laboratory testing, and environmental risk assessments and remediation. PMID- 20357607 TI - Toward a taxonomy of public health error. PMID- 20357608 TI - Challenges involved in the Salmonella Saintpaul outbreak and lessons learned. AB - A 2008 multistate food-borne outbreak of Salmonella Saintpaul caused more than 1 400 illnesses in the United States. Although initial investigations suggested tomatoes as the potential vehicle, jalapeno and serrano peppers were subsequently found positive for the outbreak strain. The uncertainty associated with this incident caused government, industry, and the public to question the efficacy of the US food safety system. Examination of the response to this incident exposed breakdowns in several areas. Communication at all levels was lacking, leading to an absence of coordinated actions and conflicting risk communication messages. Variations in resources between local and state health departments created delays in gathering accurate information for epidemiological investigations. Although new laws required increased documentation, rapid and thorough traceback of products remained elusive. Three factors contributed to the difficulty in the Salmonella Saintpaul outbreak, including (1) delayed response due to discrepancies in available resources and expertise at state and local levels, (2) inadequate communication between stakeholders and agencies, and (3) poor traceability capabilities. Future responses to food-borne illness outbreaks may be improved by addressing these three factors. PMID- 20357609 TI - Show me the money: state contributions toward STD prevention, 2007. AB - The importance of state investment in sexually transmitted disease (STD) prevention has been discussed since the mid-1990s; however, little has become known about state public health funding for STD prevention. To establish a baseline understanding of state STD prevention funding, financial data for fiscal year 2007 were gathered by survey of state STD, immunization, laboratory, and hepatitis program directors. Results revealed that on average states funded 25.8 percent of their total STD prevention budgets and invested $0.23 per capita in STD prevention. The percentage of state funding in the total state STD prevention budget ranged from 0 percent to 70.2 percent, and state investment in STD prevention ranged from $0.00 to $1.55 per capita. The direction and expenditure of state STD prevention resources was also examined. This study strengthens the national understanding of what states are doing to fund STD prevention, and it broadens state public health awareness of the overall STD prevention investment at the state level. The inclusion of Medicaid data and expenditure of federal resources by states would strengthen the study and assist longitudinal analyses focused on the impact of investment on epidemiologic indicators. PMID- 20357610 TI - Legal prison tattooing centers: viable health policy initiative? AB - Tattooing exemplifies several important links between criminal justice systems, public health, custodial management, and the social organization and behavior of prisoners. This commentary examines the efficiency of setting up legal, prison financed tattooing centers as a way of discouraging illicit tattooing and minimizing bloodborne disease transmission risks in prison settings. The author posits that the impact of legal prison tattooing centers is unlikely to be significant since less than 5 percent of bloodborne infectious diseases have been reliably attributable to tattooing, either in prison or in community settings. Behavioral studies indicate that prisoners at the highest risk of contracting bloodborne infections would probably not utilize legal prison tattooing services. Furthermore, such a service is likely to be very expensive relative to potential health benefits. Strategies focussed on reducing injecting drug use among prisoners will yield greater benefits for reducing bloodborne disease transmission per dollar spent compared with setting up legal prison tattooing parlors. Social marketing of temporary tattooing alternatives (eg, henna tattoos) to traditional illicit tattooing techniques in prison settings is potentially valuable, as temporary tattoos pose no infection risk and may also facilitate reduction in occupational and social stigma associated with many illicit prison tattoos. PMID- 20357612 TI - Planning for organizational possibilities. AB - The National Association of County and City Health Officials (NACCHO) is the national organization representing local health departments. It supports efforts that protect and improve the health of all people and all communities by promoting national policy, developing resources and programs, seeking health equity, and supporting effective local public health practice and systems. PMID- 20357611 TI - Hospital discharge data: can it serve as the sole source of case ascertainment for population-based birth defects surveillance programs? AB - INTRODUCTION: Because of the relatively high expense of collecting primary data and limited resources, electronically available, population-based hospital discharge data have been increasingly used for disease surveillance by public health researchers. The objective of this study was to compare the New York State Congenital Malformations Registry (CMR) data, which relies on hospital reports, with the hospital discharge files to identify cases in the CMR that were missed in the hospital discharge data files. The ultimate goal was to evaluate whether hospital discharge data can serve as the sole source of case ascertainment for a population-based birth defects surveillance program. METHODS: CMR cases that were born to the New York State residents for the years 2000 to 2005 were selected and matched to the hospital discharge files from the New York Statewide Planning and Research Cooperative System (SPARCS) for the same birth year period. Since the SPARCS database does not contain patient's name, extensive database matching and manual review by staff members were performed using identifying variables such as the hospital's permanent facility identifier, child's date of birth and medical record number, and mother's medical record number and residential address. RESULTS: Out of 66 757 CMR cases selected for the study period, 62 118 cases (93.1%) were matched to SPARCS hospital discharge records with International Classification of Diseases, Ninth Revision (ICD-9) codes that were reportable to the CMR, 3 444 cases (5.2%) were matched to SPARCS records with ICD-9 codes that were not reportable to the CMR, and 1 195 cases (1.8%) were not matched. The percentage of cases with multiple congenital malformations was significantly higher (21.3%) for the matched cases that had reportable ICD-9 codes in SPARCS, compared with that for matched CMR cases that had no reportable ICD-9 codes in SPARCS (10.2%). CONCLUSION: The study found that 93% of CMR infants selected for the study were matched to hospital discharge records with at least one ICD-9 code that was reportable to the CMR; 87 percent had reportable ICD codes in SPARCS that were exactly matched to those in the CMR, that is, all the birth defect codes in SPARCS were matched to those in the CMR. Thus, about 7 percent of CMR children with birth defects would have been missed if only hospital discharge files were used to ascertain the birth defect cases, indicating that there are limitations to using hospital discharge files as the sole source of case ascertainment for population-based birth defects surveillance programs. PMID- 20357613 TI - Taking programs to scale: a phased approach to expanding proven interventions. PMID- 20357614 TI - Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. PMID- 20357615 TI - Osteoblastosis and activating epidermal growth factor receptor mutations: a relationship? PMID- 20357616 TI - Clinicopathologic analysis of multiple (five or more) atypical adenomatous hyperplasias (AAHs) of the lung: evidence for the AAH-adenocarcinoma sequence. AB - OBJECTIVE: Clarification of the clinicopathologic characteristics of patients with multiple atypical adenomatous hyperplasias (AAHs). MATERIALS AND METHODS: The subjects were 1,639 patients who underwent lobectomy or pneumonectomy for lung tumors. The clinicopathologic features of the AAHs in the lung background and the main tumors were examined with regard to the number and the size of the AAHs, the incidence and histology of adenocarcinomas (ADs), and the outcome. RESULTS: Thirty-two patients (2.0%) had 5 or more AAHs (ranging from 5 to 171), being present predominantly in the upper lobe (86%) and in women (75%). Among the 794 AAHs, 495 (62%) measured less than 1 mm, 170 (22%) measured 1 to less than 2 mm, 118 (15%) measured 2 to less than 5 mm, and 11 (1%) measured 5 to less than 10 mm. Twenty-eight patients (88%) had AD (1 in 18 patients and 2 to 6 in 10 patients). Thirty-two of the 51 patients with ADs (63%) had an AAH component. The incidence of ADs among the total of both AAHs and ADs was 6.0% (51 of 845). The 5 year cancer-free survival rate was 71.4%. CONCLUSION: Five or more AAHs were seen in the background in 2.0% of lung tumors. Most of the AAHs were small, measuring less than 2 mm, and few exceeded 5 mm. Most of the patients had ADs, which were histologically suggested to be derived from AAH. However, the incidence of the AAH-AD sequence was considered to be low at the tumor basis, and the outcome of ADs was not very favorable. PMID- 20357617 TI - Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma. AB - INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy so diagnosing MPM early is very important. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for MPM. Here, we investigated the serum levels of VEGF in patients with MPM in comparison with a population that had been exposed to asbestos without developing MPM. METHODS: Serum concentrations of VEGF were measured in 51 patients with MPM and 42 individuals with benign asbestos-related diseases (asbestosis or pleural plaques) or who were healthy despite asbestos exposure. RESULTS: We demonstrated that patients with MPM had significantly higher serum levels of VEGF than a population who had been exposed to asbestos but had not developed MPM, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage patients with MPM. The difference in overall survival between the groups with VEGF serum levels lower and higher than the assumed cutoff of 460 pg/ml was significant. CONCLUSIONS: Our data suggest that the VEGF serum concentration could be a useful marker for screening MPM among asbestos exposed individuals and as a prognostic factor. PMID- 20357618 TI - Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer. AB - INTRODUCTION: In 2003, consolidation docetaxel was a promising concept for unresectable stage IIIA/B nonsmall cell lung cancer (NSCLC). To test the hypothesis that chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel would be feasible and clinically active, we conducted a phase II study. METHODS: Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks. Concurrent radiotherapy was administered more than 7 weeks to a total dose of 63 Gy in 35 fractions. Consolidation docetaxel (75 mg/m) was administered every 3 weeks for 3 doses 4 weeks after chemoradiotherapy. The primary end point was objective response rate by RECIST. RESULTS: Complete responses occurred in 4 patients and partial responses occurred in 14, for an objective response rate of 56.3% (95% confidence interval [CI], 37.7-73.6%). Median progression-free survival was 6.5 months (95% CI, 4.6-13.5); median duration of survival was 14.8 months (95% CI, 6.9-27.3). The most common hematologic toxicity was leukopenia, which were grade 3 or 4 in 16 patients (50%). Radiation pneumonitis (grade >or=2) occurred in 13 of 31 treated patients (42%). CONCLUSIONS: These findings suggested that concurrent chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel is clinically active based on median survival in patients with unresectable stage III NSCLC; however, the 42% incidence of clinical radiation pneumonitis was unexpected and warrants further investigation to determine the mechanism and preventive strategies. PMID- 20357619 TI - Possible delayed cut-end recurrence after limited resection for ground-glass opacity adenocarcinoma, intraoperatively diagnosed as Noguchi type B, in three patients. AB - INTRODUCTION: In our limited resection trial of pulmonary peripheral ground-glass opacity (GGO) lesions from 1998 to 2002, limited resection of Noguchi type A and B carcinomas seemed to have a positive outcome. However, recently three of the 24 patients, with mixed GGO lesions intraoperatively diagnosed as type B, developed a solid lesion at the cut-end scar. METHODS: Medical records and radiology and pathology findings of the three patients were reviewed. We also analyzed epidermal growth factor receptor gene mutations when possible. RESULTS: Radiologically, these three second tumors were clearly cut-end scar area recurrences. However, other pathologic and mutation findings suggest metachronous primary cancers developed in Case 1, cut-end recurrence in Case 2, and needle biopsy implantation in Case 3. It is difficult to definitively conclude whether the second tumors were recurrences or metachronous primaries. CONCLUSIONS: These second tumors have convinced us that our initial caution in concluding GGO lesions can be cured by limited resection was very appropriate. The recurrences definitely indicate that continuing follow-up attention for more than 5 years is needed after limited resection even for GGO bronchioloalveolar carcinomas. PMID- 20357620 TI - Is cytology reliable for epidermal growth factor receptor gene evaluation in non small cell lung cancer? AB - BACKGROUND: Epidermal growth factor receptor (EGFR) gene copy number has been proposed as predictor of response to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer (NSCLC). METHODS: Cytologic and matched histologic samples from 33 primary non-small cell lung cancers were analyzed by fluorescence in situ hybridization (FISH) for epidermal growth factor receptor gene. RESULTS: FISH was positive in 52% and negative in 35% of the 31 matched evaluable samples. Four of 31 (13%) cases were discordant (K = 0.736; p < 0.001). CONCLUSION: Our data support the feasibility and reliability of epidermal growth factor receptor gene assessment by FISH on cytology. PMID- 20357621 TI - Osteoblastic bone lesions developing during treatment with erlotinib indicate major response in patients with non-small cell lung cancer: a brief report. AB - BACKGROUND: The osteoblastic bone flare or response is the paradoxical phenomenon of increase in the quantity and/or density of bone lesions in the presence of well-documented disease response to treatment in other tumor sites. It results from the rapid repair and increased osteoblastic activity in bone metastases responding to therapy and therefore represents treatment efficacy. Nevertheless, no reliable markers can differentiate an osteoblastic flare or response from disease progression. In non-small cell lung cancer (NSCLC) osteoblastic bone flare or response has been reported in only a few patients. METHODS: Pre- and posttreatment CT scans of NSCLC patients with osteolytic bone lesions and treated with erlotinib as a single treatment modality were reviewed. RESULTS: In 3 cases fulfilling these criteria and responding to erlotinib according to RECIST criteria, an osteoblastic bone response was found. With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitors in patients with NSCLC harboring mutations predicting a good response, the osteoblastic response will likely be increasingly seen. Awareness of this phenomenon with epidermal growth factor receptor tyrosine kinase inhibitors is important for physicians treating patients with NSCLC, so that it is not misinterpreted as progressive disease resulting in premature cessation of effective therapy. PMID- 20357622 TI - Primary pulmonary T-cell lymphoma in a human T-lymphotropic virus type-1 carrier showing atypical shadow. PMID- 20357623 TI - Synchronous primary lung cancer, breast cancer recurrence, and mediastinal silicon-induced lymphadenitis. PMID- 20357624 TI - S-1 plus cisplatin chemotherapy with concurrent radiation for thymic basaloid carcinoma. PMID- 20357625 TI - Solitary choriocarcinoma in the lung. PMID- 20357626 TI - Resection of mucinous lung adenocarcinoma presenting with intractable bronchorrhea. PMID- 20357628 TI - Caudal border of level 2R in the new international lymph node map for lung cancer. PMID- 20357629 TI - Cavitary lung cancer with an aspergilloma-like shadow. PMID- 20357630 TI - BAHA in single-sided deafness: patient compliance and subjective benefit. AB - OBJECTIVE: Despite most patients with single-sided deafness (SSD) after operation for acoustic neuroma (AN) perceiving a significant hearing handicap, less than 25% are interested in bone-anchored hearing aid (BAHA) implantation. We evaluated the treatment compliance of BAHA in SSD and the effect of BAHA on the subjective handicap. METHODS: Part 1: It was determined, from our first study, how many of the SDD patients after operation for AN (n = 59) and interested in BAHA (n = 14) had been implanted. Part 2: Of 23 BAHA-implanted patients with SSD due to various causes, including the implanted patients from the previous study, 21 answered a questionnaire on the BAHA treatment compliance and the subjective handicap with and without BAHA. RESULTS: Part 1: Of the 14 patients from our first study who were interested in implantation for BAHA, 11 had been implanted (18.6% of all 59 patients). Part 2: Of the 21 patients with SSD, 95% still used BAHA, and of these, 81% used it more than 8 hours a day. Of the patients, 90% considered BAHA a moderate to significant aid; it reduced the subjective hearing handicap from 7.4 to 2.3 arbitrary units on a visual analog scale. CONCLUSION: Despite the subjective handicap perception among most patients with SSD after AN surgery, less than 20% chose treatment with BAHA. Conversely, patients with SSD choosing implantation had high treatment compliance and felt that BAHA reduced their handicap. Thus, when selected by the patients after testing, BAHA is effective in SSD and results in a high patient compliance. PMID- 20357631 TI - De visione, voce et auditu: the contribution of Hieronymous Fabricius to our understanding of tensor tympani function. AB - STUDY DESIGN: This work reviews the literature concerning the life and scientific contributions of Hieronymous Fabricius (1533-1619). We also analyze the translated Latin text that focuses on the middle ear muscles from a first edition of Fabricius' book entitled 'De Visione, Voce et Auditu' (The Vision, Voice and Hearing, 1600). RESULTS: Hieronymous Fabricius was one of the first scientists to introduce structure-function relationships in anatomic research. Better known for his descriptions of venous valves and human fetal development, his major contribution to otology was his theory on tensor tympani (TT) function. The TT is 1 of 2 middle ear muscles whose function has undergone a long period of speculation since its discovery by Vesalius (1514-1564) and description by Eustachius (1510-1574). Fabricius' theory of TT physiology was described in his treatise 'De Visione, Voce et Auditu' (1600). He wrote that the TT "protected" the tympanic membrane and helped in middle ear ventilation. In the 20th century, the development of the acoustic impedance measuring bridge by Otto Metz (1905 1993) allowed for the first objective measurements of middle ear function. Experiments on human subjects with various ear pathologies confirmed that the stapedius was the dominant sound evoked middle ear muscle. However, Fabricius' original theory on the TT's role in middle ear ventilation persists to this day based on recent physiologic, embryologic, and histologic studies. CONCLUSION: Hieronymous Fabricius was a pioneer in approaching anatomy from a structure function relationship, and was an active proponent for maximizing the learning environment for students. Fabricius' writings provided the foundation for contemporary theories on the role of the TT, and he proposed those ideas during an era when great strides were being made to increase our understanding of ear anatomy and physiology. PMID- 20357632 TI - Middle ear cholesteatoma extending into the petrous apex. PMID- 20357633 TI - The long prosthesis syndrome. PMID- 20357635 TI - Acute cervical fractures in ankylosing spondylitis: an opportunity to correct preexisting deformity. AB - STUDY DESIGN: A new technique for the management of traumatic cervical fracture in patients with chin-on-chest deformity in ankylosing spondylitis is presented. OBJECTIVE.: To present a new surgical technique for acute deformity correction through cervical fractures in the setting of kyphotic deformities. SUMMARY OF BACKGROUND DATA: Cervicothoracic kyphotic deformity in ankylosing spondylitis is currently treated with extension osteotomy in an elective setting. In elective extension osteotomies, the surgeon manipulates the head to generate osteoclasis, temporarily producing an unstable cervical fracture. Cervical fractures in ankylosing spondylitis are highly unstable and frequently associated with neurologic compromise. Most reports describe either no reduction and fixation in situ or reduction in preoperative traction followed by fixation. METHODS: A 60 year-old man with chronic ankylosing spondylitis and profound kyphotic deformity suffered a traumatic lower cervical spine fracture. He was treated with an acute cervical spine extension osteotomy through the fracture site using an anterior lengthening bar modification to a halo vest. The anterior lengthening bar allows controlled extension of the neck without manual manipulation by the surgeon. RESULTS: This patient presented with a chin-brow angle of approximately 90 degrees and was corrected to approximately 5 degrees to 8 degrees . No immediate or delayed complications were seen. After halo vest treatment for 3 months, an excellent postural correction was obtained. CONCLUSION: Surgical extension osteotomy in the lower cervical spine through the fracture site using the anterior lengthening bar-halo extension brace seems to be a safe method for correcting spine flexion deformity in ankylosing spondylitis after traumatic fracture. PMID- 20357637 TI - Understanding bony safety zones in the posterior iliac crest: an anatomic study from the Hamann-Todd collection. AB - STUDY DESIGN: Morphometric analysis of the human ilia obtained from the Hamann Todd Collection at Cleveland Museum of Natural History. OBJECTIVE: To identify whether gender and pelvis size affect the distances between anatomic landmarks of the posterior pelvis. SUMMARY OF BACKGROUND DATA: The iliac crest bone harvest is commonly performed in orthopedic, neurosurgic, and maxillofacial surgery. Morbidity from the bone graft harvest is well described (Arrington et al, Clin Orthop Relat Res 1996:300-9; Ebraheim et al, J Am Acad Orthop Surg 2001;9:210-8; Hu and Bohlman, Clin Orthop Relat Res 1994;208-13; Kahn, Clin Orthop Relat Res 1979;204-7; Kurz et al, Spine 1989;14:1324-31; Lim et al, Spine 1996;21:2376-8; Sasso et al, J Bone Joint Surg Am 1998;80:631-5; St. John et al, A J Orthop (Belle Mead NJ) 2003;32:18-23; Summers and Eisenstein, J Bone Joint Surg Br 1989;71:677-80). Several studies have advanced our understanding of the bony, vascular, and neurologic anatomy of the posterior iliac crest (Ebraheim et al, J Am Acad Orthop Surg 2001;9:210-8; Xu et al, Spine 1996;21:1017-20). There is no literature documenting the measurement of this region on a large, statistically significant scale. METHODS: An anatomic study was undertaken using the Hamann Todd collection. The bilateral human ilia were examined from 50 men and 50 women between 18 and 80 years of age. Age, gender, and side were recorded. Four parameters were recorded: the shortest distance from the posterior superior iliac spine to the sciatic notch (PN), the shortest distance from posterior superior iliac spine to the sacroiliac joint (PS), the anterior-posterior length of the sciatic notch (P90), and the maximum length of the sacroiliac joint (SI). RESULTS: The right and left ilia were compared, and no significant difference was found. The mean for all 4 measurements was slightly larger in men and statistically significant (PN: men 43.7 +/- 4.6 mm vs. women 39.7 +/- 5.8 mm; PS: 21.5 +/- 7.8 mm vs. 16.9 +/- 5.3 mm; P90: 16.7 +/- 3.8 mm vs. 15.3 +/- 3.6 mm; SI: 60.0 +/- 5.9 mm vs. 55.2 +/- 5.8 mm). The ranges and distribution of data within the ranges were compared. Men had higher maximum limits although the lower limits were similar (PN: men 28.7-62.7 mm vs. women 28.0-51.0 mm; PS: 7.3-43.3 mm vs. 4.7-34.3 mm; P90: 9-25.3 mm vs. 7.7-22.7 mm; SI: 42.3-69 mm vs. 50.0-79.0 mm). CONCLUSION: This study defines distances in the posterior iliac crest beyond which the risk of injuring important structures is present (2.80 cm for 100% of the population or 3.00 cm for > or = 90%). PMID- 20357638 TI - The influence of intervertebral disc shape on the pathway of posterior/posterolateral partial herniation. AB - STUDY DESIGN: Basic scientific investigation employing the medical imaging techniques of contrast-enhanced plane film radiographs and computed tomography in addition to gross dissection techniques on a sample of spines. OBJECTIVE: To document the specific posterior/posterolateral pathway of mechanically-induced intervertebral disc (IVD) herniation as the result of repetitive loading and disc geometry. SUMMARY OF BACKGROUND DATA: In vitro cadaveric and animal investigations have indicated that the posterior/posterolateral aspects of the IVD are most susceptible to damage leading to herniation, and that cyclic bending is the most potent variable influencing herniation. The IVD in horizontal cross section ranges in shape from ovoid to limacon (kidney-shaped) which influences stress distributions. The purpose of this investigation was to determine the role of the IVDs shape and size on influencing the pathway of herniation. METHODS: Compressive loads (1472 N) in conjunction with 7000 repetitive cycles of flexion extension were applied to 22 porcine motion segments. Computed tomography images and contrast-enhanced plane file radiographs, in addition to dissection techniques were used to evaluate the progression of herniations. A logistical regression assessed the links between endplate size and shape, and the probability of a specific herniation type (directionally diffuse or directionally concentrated). RESULTS: A total of 18 out of the 22 specimens exhibited detectable anular damage in the posterior/posterior lateral direction. Of the 18 specimens, 17 were partial herniations while one incurred a full herniation. IVD shape was found to be predictive of the pathway of herniation (P = 0.0329); oval IVD shapes were more likely to herniate in a directionally diffuse manner (6/18), while limacon IVDs were more likely to herniate in a directionally concentrated manner (12/18). CONCLUSION: The shape of the IVD appears to be predictive of the pathway of IVD herniation. PMID- 20357640 TI - Cleland JA, Fritz JM, Kulig K, et al. Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule. A randomized clinical trial. Spine 2009;34:2720-9. PMID- 20357641 TI - Re: Gouveia LO, Castanho P, Ferreira JJ. Safety of chiropractic interventions: a systematic review. Spine 2009; 34:E405-13. PMID- 20357643 TI - Re: Chou R, Atlas SJ, Stanos SP, et al. Nonsurgical interventional therapies for low back pain: a review of the evidence for an American Pain Society clinical practice guideline. Spine (Phila Pa 1976) 2009;34: 1078-93. PMID- 20357644 TI - Re: Furlan AD, Imamura M, Dryden T, et al. Massage for low back pain: an updated systematic review within the framework of the Cochrane Back Review Group. Spine 2009;34:1669-84. PMID- 20357646 TI - Traffic collisions between electric mobility devices (wheelchairs) and motor vehicles: Accidents, hubris, or self-destructive behavior? AB - OBJECTIVE: This study had its genesis in a personally observed collision between a motor vehicle and a motorized wheelchair (electric mobility device) on a busy street in the middle of the block at an unmarked crossing. To the observer, at the time, this appeared to be a suicidal act. This investigation was initiated to both delineate the number of these crashes nationally and understand this phenomena as a potentially planned act of self-destruction. DESIGN: An initial survey of police reports was immediately frustrated by an inability to separate motor vehicle and electric mobility device collisions from the much larger group that involved ambulatory citizens because both types were classified together as "pedestrian" accidents. Instead, the search engine NexisLexis was used to identify 107 newspaper articles each of which described a motor vehicle and electric mobility device accident. RESULTS: In the motor vehicle and electric mobility device collisions, men predominated women (3:1 ratio) with an average age of 56 yrs. Sixty of these accidents were fatal. Ninety-four percent involved an electric mobility device and 6% a manual wheelchair. In 50% of the cases, the motor vehicle was a truck, van, or sport utility vehicle. Fifty percent occurred at dusk or dawn or at night. The electric mobility device occupant was cited as the guilty party in 39% of the cases and the driver of the motor vehicle in 27%. Twenty percent were unwitnessed hit-and-run accidents, whereas "no fault" was found in 8% of the cases. CONCLUSIONS: Although many accidents do happen by chance, when an electric mobility device operator openly challenges busy traffic by attempting to traverse it in the middle of the block at an unmarked crossing, predisposing psychosocial factors must also be considered. Hubris or premeditated self-destructive behavior or both need to be explored as preeminent issues with reference to the prodromal of the "accident process." PMID- 20357647 TI - Preamputation evaluation of lower-limb skeletal muscle perfusion with H(2) (15)O positron emission tomography. AB - OBJECTIVE: To establish whether muscle blood flow (MBF) measurements with O-water positron emission tomography could reliably identify patients with critical limb ischemia and detect and quantify a distal deficit in skeletal MBF in these cases. DESIGN: O-water positron emission tomography scans were performed at rest or during unloaded ankle plantar and dorsiflexion exercise of the diseased leg in 17 subjects with leg ischemia or on a randomly selected leg of 18 age-matched healthy control subjects. TcPO2 was evaluated with Novametrix monitors and perfusion of skin topically heated to 44 degrees C and adjacent nonheated areas with a Moor Instruments laser Doppler imaging scanner. RESULTS: The enhancement of MBF induced by exercise was significantly lower in ischemic than in normal legs, and the sensitivity and specificity of this phenomenon were similar to those of laser Doppler imaging or TcPO2 in identifying ischemia subjects. In addition, the exercise MBF deficit was predominant at the distal-leg levels, indicating the ability of the technique to help determine the correct level of amputation. CONCLUSIONS: Skeletal MBF of legs with severe ischemia can be detected accurately with O-water positron emission tomography and could add valuable information about viability of skeletal muscle in the residual limb when deciding the level of an amputation. PMID- 20357648 TI - Relapsing and remitting scapular winging in a pediatric patient. AB - Scapular winging (scapula alata) is a condition in which the scapula is rotated or displaced away from the body. The nature of this rotation or displacement can vary depending on the origin. There are many different causes of scapular winging including neurogenic, structural, muscular, and bursal (Frontera, Silver, Essentials of Physical Medicine and Rehabilitation. Philadelphia, Hanley and Belfus, 2002, pp 99-102). Structural causes are not frequently at the top of a clinician's differential diagnosis, but they must always be considered. We review the case of a teenage boy who developed intermittent scapular winging after tackling his brother in a backyard football game. His symptoms resolved and recurred over a period of 9 mos. Approximately 1 yr after the initial episode of winging, during a recurrence of his symptoms, a repeat shoulder x-ray was ordered. This study revealed a previously undetected osteochondroma. The patient subsequently underwent resection of the inferior angle of his right scapula and had complete resolution of his symptoms. PMID- 20357649 TI - Validation of the central blood pressure estimation by the SphygmoCor system in Chinese. AB - BACKGROUND: Pulse wave analysis using the SphygmoCor system allows the estimation of central blood pressures (BP). However, there is controversy over its accuracy for clinical use. METHODS: In 45 patients undergoing coronary angiography, we compared the ascending aorta BPs measured by the invasive catheter with the estimations by the SphygmoCor system, using paired t-tests, simple correlation analysis, and Bland-Altman plots. RESULTS: The estimation of central systolic BP by SphygmoCor was lower, although statistically insignificant, than that measured by the catheter (144+/-29 vs. 148+/-30 mmHg; P=0.98). The standard deviation of the difference amounted to 17 mmHg. Both the measured and estimated central systolic BPs were significantly (P<0.001) lower than the brachial systolic BP (156+/-30 mmHg). The diastolic BP measured at the brachial artery (87+/-15 mmHg) and provided by SphygmoCor (90+/-15 mmHg) were systematically higher (P<0.001) than that measured by the catheter (74+/-13 mmHg). The SphygmoCor system underestimated the central pulse pressure by -20+/-14 mmHg compared with the catheter method. The correlation coefficients for systolic BP, diastolic BP, and pulse pressure between catheter measurements and the SphygmoCor estimations were 0.84, 0.60, and 0.82 (P<0.001), respectively. CONCLUSION: When the radial waveform was calibrated with the oscillometric brachial pressures, the SphygmoCor system could not provide accurate estimation of central BPs. The inaccurate measurement of cuff pressure was the major limiting factor for the use of the transfer function in the clinical settings. PMID- 20357650 TI - Nurse autonomy in cancer care. AB - BACKGROUND: The concept of autonomy is regarded as an essential element for gaining professional status. Yet, it remains poorly defined and understood. To date, there is little research that has focused on exploring how nurses in different specialty areas perceive autonomy. OBJECTIVE: The purpose of this research was to explore oncology nurses' perceptions of autonomy and understand how they develop and exhibit autonomy in their everyday practice. METHODS: Using Leininger's ethnonursing method, data were collected from 15 oncology nurses using semistructured interviews. Participant observation was also carried out through job shadowing to complement interview data. RESULTS: Three themes emerged from the findings: autonomy is an unspoken opportunity in the workplace; autonomy is developed through professional and personal growth acquired over time; and demonstrating autonomous behaviors is a conscious choice. CONCLUSION: The findings provide insight into how oncology nurses perceive, develop, and exhibit autonomy in everyday practice and how autonomous and collaborative clinical decision making contributes to quality cancer care. IMPLICATIONS FOR PRACTICE: Descriptions of the meaning of autonomy and its explication in a nursing specialty practice can add to nursing knowledge by clarifying nurse autonomy and its relevance to nurses' work life. Descriptive studies can identify nurse behaviors and attitudes related to autonomy that may be measurable and relevant to real life. PMID- 20357651 TI - Examining the most relevant conceptualization of the socioeconomic status construct for cancer research. AB - BACKGROUND: Although previous research has established a link between socioeconomic status (SES) and cancer outcomes, there is still little understanding of the processes that contribute to these outcome disparities. OBJECTIVE: This study aimed to describe the ways a family's SES influences their healthcare behavior after a child is diagnosed with cancer. METHODS: The sample included 5 case study families and in-depth interviews with 21 parents. Case study families were interviewed and observed once a month for 6 months. RESULTS: Parents' finances influenced their ability to maintain household expenses and to pay for healthcare expenses and household help. Wealth and help from friends and family are important aspects of families' financial statuses. Parents' educational attainment affected their ability to understand diagnosis and treatment options, their confidence and communication with healthcare professionals, and the utility of their social networks. Parents' occupation influenced their work schedule flexibility, fringe benefits, and their access to and quality of employer-sponsored health insurance. CONCLUSIONS: Findings suggest that 3 overarching domains of SES (eg, financial, education, and occupation) have important implications for parents' healthcare navigation. This study underscores the need to use a nuanced set of SES measures (beyond income and education) in future research to enhance our understanding of how SES affects healthcare navigation and refine intervention initiatives designed to help reduce health disparities. IMPLICATIONS FOR PRACTICE: Cancer education initiatives should focus on enhancing patient-provider interactions, health communication, accessing health information, and resolving work and financial barriers to cancer care. PMID- 20357652 TI - Patterns of the use of complementary and alternative medicine in women with metastatic cancer. AB - BACKGROUND: Complementary and alternative medicine (CAM) has been widely used in the general population and in patients with cancer. Female sex and advanced cancer are 2 reported factors contributing to CAM use. OBJECTIVE: The aim of this study was to examine the patterns of CAM use among women with metastatic cancer. METHODS: A total of 68 women were enrolled into this cross-sectional study. All participants were receiving conventional treatment in a single inpatient oncology center. Data were collected from the women through a face-to-face interview guided by a questionnaire. On the basis of women's responses, all participants were divided into 2 groups: CAM users and nonusers. RESULTS: The 2 cancers most frequently diagnosed in these women were gastrointestinal cancer (36.8%) and breast cancer (33.8%). Of 68 women, 40 (58.8%) reported the use of at least 1 type of CAM therapy after the diagnosis of cancer. There were no significant differences in the sociodemographic and clinical characteristics between CAM users and nonusers (P > .05). The most frequently used CAM method was herbal therapy (34.6%) and the second was nutritional supplements (17.9%). A considerable proportion (60.0%) of CAM users had not discussed their CAM use with their physicians or nurses. Four (10%) patients reported an adverse effect due to CAM use. CONCLUSIONS: Our findings indicate that Turkish women with metastatic cancer seek to use CAM, with a small minority being at risk of potential adverse effects of certain CAM products. IMPLICATIONS FOR PRACTICE: Because of the high prevalence of CAM therapies among women with metastatic cancer, oncology specialists and nurses should increase their knowledge about CAM therapies. Nurses are in a position to provide knowledge and education about CAM therapies and to develop protocols and guidelines about CAM use for patients with cancer. PMID- 20357653 TI - Diffusion effects of an inpatient hospice unit on improving the parent hospital's pain management of terminally ill cancer patients not receiving hospice care in Taiwan. AB - BACKGROUND: The impact of hospice care on cancer-pain management at the institutional level of an acute-care hospital setting has not been addressed in prior research. OBJECTIVE: The aim of the study was to investigate the diffusion effects of an inpatient hospice unit on improving the parent hospital's quality of pain management. METHODS: A convenience sample of 1370 terminally ill cancer patients not receiving hospice care in Taiwan measured pain relief experiences and perceived pain-management practices of healthcare professionals. RESULTS: Taiwanese terminally ill cancer patients in the with-hospice group were 2.40 times (95% confidence interval [CI], 1.53-3.76]) more likely than those in the without-hospice group to report their pain as not controlled before hospital admission. However, after patients with uncontrolled pain were hospitalized, they were equally as likely as those in the without-hospice group to report pain as not yet been relieved when interviewed (adjusted odds ratio, 1.42; 95% CI, 0.77 2.64). Patients in the with-hospice group were (1) less likely to complain about waiting too long for pain medication (adjusted odds ratio, 0.41; 95% CI, 0.18 0.93) and (2) more or as likely to rate the amount of pain medication received as adequate (depending on the status of adequate pain control before admission) than/as those from hospitals without an inpatient hospice unit. CONCLUSION: Hospice care may add value at the institutional level by effectively and appropriately managing cancer pain of Taiwanese terminally ill patients not receiving hospice care. IMPLICATIONS FOR PRACTICE: Translation of evidence-based strategies to manage cancer pain could be facilitated by expanding collaboration between hospice-care professionals and other healthcare professionals both within and among institutions. PMID- 20357654 TI - A systematic review of oral assessment instruments: what can we recommend to practitioners in children's and young people's cancer care? AB - BACKGROUND: Observing and recording the signs and symptoms of oral mucositis are an important part of oral care, essential to the prevention and treatment of mucositis. Structured oral assessment enables a more informed and accurate identification of signs and symptoms and will enable early and individualized interventions. OBJECTIVE: A United Kingdom-based mouth-care group conducted a systematic review of the published literature through to March 2004 and repeated in 2008. The goal of this review was to identify and evaluate the range of instruments used to assess oral mucositis to recommend in evidence-based guidelines the "best" instrument to use in the field of children's and young people's cancer care. METHODS: Search sources included the Cochrane Library, MEDLINE, EMBASE, and CINAHL. Studies were selected using defined criteria and reviewed by 3 pairs of group members. RESULTS: Fifty-four individual oral assessment instruments were identified with only 15 reporting evidence of reliability and validity testing. Only 3 articles reported on oral assessment exclusively in our population. CONCLUSIONS: The guidelines recommend only 1 assessment instrument, the Oral Assessment Guide, or adaptations of this instrument, to be used in clinical practice. Five factors influenced this recommendation: purpose of assessment, population, outcomes assessed, and quality of the instrument and ease of use. IMPLICATIONS FOR PRACTICE: The Oral Assessment Guide has been consistently judged to be user-friendly and appropriate for everyday clinical practice with both adults and children, as well as a useful research tool. PMID- 20357655 TI - Effectiveness of peer education for breast cancer screening and health beliefs in eastern Turkey. AB - BACKGROUND: The primary site of cancer in Turkish women is breast cancer. The incidence of breast cancer is increasing in Turkey. OBJECTIVE: The aim of the research was to educate women 40 years and older to increase their awareness on early detection and diagnosis, to facilitate the use of the early diagnosis methods, to improve the women's beliefs in relation breast cancer, and to increase the use of Cancer Early Diagnosis and Screening Centers available in the city. METHODS: The target population of the research was 5000 women. Forty selected women were educated as peer educators. Twenty-five of them were selected as principal peer educator. Each peer educator was expected to educate 200 women. Peer trainers educated their peer and also arranged for the mammography appointment of the women who decided to have theirs taken. Data were obtained before and after the training by Champion's Health Belief Model Scale, questionnaire forms, and Cancer Early Diagnosis and Screening Centers data for mammography practice. RESULTS: Breast cancer was detected in 8 women. Statistical analyses showed positive changes in women's health beliefs and breast self examination knowledge. There were 20.4% of women (n = 1040) who did get mammograms, and 8% (n = 8) of women were found to have cancer in all of those screened. CONCLUSION: Peer education was found to be effective for increasing the knowledge, beliefs, and practice of women related to breast cancer. IMPLICATIONS FOR PRACTICE: Peers can reinforce learning through ongoing contact. Peer education can be used to improve early diagnosis of breast cancer and breast cancer awareness in asymptomatic women. PMID- 20357656 TI - The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. AB - BACKGROUND: Assessment of chemotherapy-induced peripheral neuropathy signs and symptoms has been hampered because of the lack of simple, reliable, and valid measures. OBJECTIVE: The study objective was to examine the internal consistency and interrater reliability as well as the structural validity of a 5-component total neuropathy score-reduced (TNSr) variant and a chemotherapy-induced neuropathy-specific Neuropathic Pain Scale. METHODS: One hundred seventeen outpatients receiving taxanes or platinums were assessed by a consistent nurse practitioner using the 2 instruments. Ten subjects participated in interrater reliability testing. RESULTS: Mean scores and SDs for individual items were low. The strength item was deleted because of low interitem correlations and a floor effect. The reflex item was deleted because of low interitem correlations and its negative influence on Cronbach alpha. Pin sensibility was deleted because of low factor loadings. The TNSr-short form and the chemotherapy-induced neuropathy specific Neuropathic Pain Scale formed 2 distinct factors, providing evidence of structural validity. Cronbach alpha's for the 2 instruments were .80 and .96, respectively. The TNSr interrater reliability results suggested acceptable rater concordance, but minor revisions could further improve scoring precision. CONCLUSION: Clinimetric evidence supports the use of 2 new instruments when monitoring taxane- and platinum-related neuropathy and pain. Further instrument modifications are recommended, followed by additional testing in diverse populations. IMPLICATIONS FOR PRACTICE: With these new instruments, nurses can more easily incorporate prospective neuropathy assessment into daily clinical practice. The outcome will be improved symptom awareness by oncology clinicians and patients, leading to fewer chemotherapy-induced peripheral neuropathy-related devastating effects on functionality and quality of life. PMID- 20357657 TI - Shielded from the real world: perspectives on Internet cancer support groups by Asian Americans. AB - BACKGROUND: Despite positive reports about Internet cancer support groups (ICSGs), ethnic minorities, including Asian Americans, have been reported to be less likely to use ICSGs. Unique cultural values, beliefs, and attitudes have been considered reasons for the low usage rate of ICSGs among Asian Americans. However, studies have rarely looked at this issue. OBJECTIVE: The purpose of this study was to explore (a) how Asian Americans living with cancer who participated in ICSGs viewed ICSGs, (b) what facilitated or inhibited their participation in ICSGs, and (c) what cultural values and beliefs influenced their participation in ICSGs. METHODS: The study was a 1-month qualitative online forum among 18 Asian American cancer patients recruited through a convenience sampling method. Nine topics on the use of ICSGs organized the forum discussion, and the data were analyzed using thematic analysis. RESULTS: Four themes emerged from the data analysis process: (a) "more than just my family," (b) "part of my family," (c) "anonymous me," and (d) "shielded from the real world." CONCLUSION: The overarching theme was Asian Americans' marginalized experience in the use of ICSGs. IMPLICATIONS FOR PRACTICE: Offering the most current information on cancer and cancer treatment is essential for nursing practice in developing a culturally competent ICSG for Asian Americans. Also, emotional familiarity should be incorporated into the design of the ICSG, and the ICSG needs to be based on nonjudgmental and nondiscriminative interactions. PMID- 20357658 TI - The relationship between optimism and quality of life in newly diagnosed cancer patients. AB - BACKGROUND: Understanding the relationships between social and psychological determinants of health-related quality of life (HRQOL) is a critical step in developing effective screening tools and targeted interventions for psychosocial care. OBJECTIVE: The purpose of this study was to examine the relationship between dispositional optimism and HRQOL in newly diagnosed adult cancer patients. METHODS: A cross-sectional, predictive correlational design was used. The sample consisted of 163 patients with mixed diagnoses and stages who were within 180 days since diagnosis and had completed a battery of psychosocial measures upon enrollment into a psychosocial data registry during their first outpatient visit or treatment. Hierarchical multiple regression analyses were conducted to determine predictors of HRQOL. RESULTS: Optimism was significantly correlated with spiritual well-being, anxiety, depression, and HRQOL. Optimism was not a significant predictor of HRQOL at initial diagnosis and treatment when age, scores on functional status, spiritual well-being, depression, and anxiety were entered into the regression equation. CONCLUSION: Dispositional optimism is not a primary factor in HRQOL at initial diagnosis and treatment. Further exploration is needed to determine if optimism exerts a greater influence on HRQOL at another point along the cancer trajectory and if there is overlap between the constructs of optimism and spirituality. IMPLICATIONS FOR PRACTICE: Although systematic screening for dispositional optimism is not recommended, patients who display characteristics associated with low optimism require further assessment. Also, patients with poor functional status, young age, low levels of spirituality, and high levels of depression may be vulnerable for poor HRQOL. PMID- 20357661 TI - An early structured psychoeducational intervention in patients with breast cancer: results from a feasibility study. AB - BACKGROUND: Although the incidence of breast cancer in Italy is high, like in most Western countries, the role of psychosocial support in disease management and outcome is incompletely understood. A structured psychoeducational group intervention has been shown by Fawzy (J Psychosom Res. 1999, 45:191-200) to increase psychological well-being and natural killer immunological reactivity in patients with melanoma, with decreased relapse rate and prolonged survival time. OBJECTIVE: The aims of the present study were to assess the feasibility of Fawzy's intervention by preliminary evaluation of its usefulness on a sample of women with early-stage breast cancer. METHODS: Psychological reaction to the disease and its possible modification by the psychoeducational treatment were determined with the Mini-Mental Adjustment to Cancer scale at the time of study recruitment and at the end of the intervention. RESULTS: A total of 29 patients participated in the study. Rate of participation and adherence to the intervention were 83% and 100%, respectively. A significant reduction in anxious preoccupation was observed in treated patients, whereas the other coping strategies identified by the Mini-Mental Adjustment to Cancer scale were not significantly modified. CONCLUSION: The results support the feasibility of the intervention. In particular, the reduction in anxious preoccupation, characterizing the early phase of adaptation to breast cancer, may be the target for psychosocial intervention including specific nursing contributions. IMPLICATIONS FOR PRACTICE: The results obtained encourage investigating in more depth and with adequate methodology the role of psychoeducational group support for patients with early-stage breast cancer. In particular, they suggest that more attention should be given to the early phase, which follows the communication of cancer diagnosis and precedes the beginning of chemotherapy, which seems to be characterized by anxious preoccupation. A further indication resulting from the study and development of psychoeducational groups for patients with cancer is the opportunity to include cancer nursing among the topics that are addressed during psychoeducational group meetings because it seems to have been neglected in the available studies despite its evident relevance in cancer care. PMID- 20357660 TI - Symptom monitoring and self-care practices among oncology adults in China. AB - BACKGROUND: Cancer is a major health problem in Asia. OBJECTIVE: This study's purpose was to examine patient-reported symptoms and self-care strategies of Chinese adults during cancer treatments. METHODS: A cross-sectional, descriptive study in cancer centers in Hong Kong and Xi'an, China, was conducted. A total of 222 patients were included: those undergoing combined radiation therapy (RT) and chemotherapy (CT) (n = 73), CT alone (n = 63), or RT alone (n = 82). Institutional review board approvals were obtained and participants provided signed consent to participate. Instruments used were the following: (a) 25-item Therapy-Related Symptom Checklist (TRSC) Chinese version, (b) Symptom Alleviation: Self-care Methods tool, (c) Karnofsky Scale and Health Form, and (d) a demographic form. RESULTS: : The TRSC-Chinese version has good reliability and validity. Chinese patients on combined RT and CT reported more symptoms with greater severity on the TRSC than did those receiving either RT or CT alone (F = 3.08, P < .05). Similar to Midwestern US findings, patients on all treatment types reported severe symptoms on TRSC subscales eating, oropharynx, nausea, fatigue, and pain. Complementary/self-care categories used were diet/nutrition/lifestyle change (most used, found helpful), mind/body control, and biologic treatments: other. CONCLUSION: The TRSC, a standardized patient report symptom checklist, facilitates symptom monitoring and management. IMPLICATIONS FOR PRACTICE: Patient-reported symptom occurrence and severity scale enable health providers to prioritize, evaluate interventions, and promote/assist patients' self-care. PMID- 20357659 TI - Trajectories of fatigue in patients with breast cancer before, during, and after radiation therapy. AB - BACKGROUND: Fatigue is a significant problem associated with radiation therapy (RT). OBJECTIVE: This study examined how evening and morning fatigue changed from the time of simulation to 4 months after the completion of RT and investigated whether specific demographic and disease characteristics and baseline severity of symptoms predicted the initial levels of fatigue and characteristics of the trajectories of fatigue. METHODS: Seventy-three women with breast cancer completed questionnaires that assessed sleep disturbance, depression, anxiety, and pain prior to the initiation of RT and the Lee Fatigue Scale, over 6 months. Descriptive statistics and hierarchical linear modeling were used for data analysis. RESULTS: Large amounts of interindividual variability were found in the trajectories of fatigue. Evening fatigue at baseline was negatively influenced by having children at home and depression. The trajectory of evening fatigue was worse for women who were employed. Morning fatigue at baseline was influenced by younger age, lower body mass index, and the degree of sleep disturbance and trait anxiety. Trajectories of morning fatigue were worse for patients with a higher disease stage and more medical comorbidities. CONCLUSION: Interindividual and diurnal variability in fatigue found in women with breast cancer is similar to that found in men with prostate cancer. However, the predictors of interindividual variability in fatigue between these 2 cohorts were different. IMPLICATIONS FOR PRACTICE: Diurnal variability and different predictors for morning and evening fatigue suggest different underlying mechanisms. The various predictors of fatigue need to be considered in the design of future intervention studies. PMID- 20357662 TI - Two adjacent microdeletions in 8q11.2 cause a phenotype suggestive of the 22q11 deletion syndrome. PMID- 20357663 TI - Fibroblast growth receptor-3 (FGFR3) G375C mutation in a case of achondroplasia and thanatophoric dysplasia phenotypic overlap. PMID- 20357664 TI - Escitalopram versus serotonin noradrenaline reuptake inhibitors as second step treatment for patients with major depressive disorder: a pooled analysis. AB - The objective of this study was to evaluate the efficacy and tolerability of escitalopram versus serotonin and noradrenaline reuptake inhibitors (SNRIs) as second step treatment (defined operationally as poor response or intolerability to an antidepressant) for major depressive disorder (MDD). Results from all eligible head-to-head clinical trials of MDD (which excluded patients who earlier failed two or more antidepressants) sponsored by Lundbeck or Forest comparing escitalopram and SNRIs (venlafaxine and duloxetine) were pooled. A second step treatment subgroup was identified, defined as patients treated earlier with any antidepressant in the 6-month period before baseline. Data from three clinical trials were included in the analysis; 132 patients were identified in the second step treatment subgroup (66 in each of the escitalopram and SNRI groups). The primary efficacy analysis showed that the patients subsequently treated with escitalopram had significantly lower Montgomery Asberg Depression Rating Scale total scores after 8 weeks compared with those subsequently treated with SNRIs (difference = -6.4, P<0.0001). Escitalopram treatment was also associated with higher clinical response (73 vs. 44%, P=0.0004) and remission rates (62 vs. 41%, P=0.0083) compared with subsequent treatment with SNRIs. Escitalopram showed a better tolerability profile with lower all-cause withdrawals from study (9 vs. 23%, P<0.04) and lower withdrawals because of adverse events (2 vs. 17%, P<0.003). In conclusion, escitalopram is associated with a better efficacy and tolerability profile than SNRIs (duloxetine and venlafaxine) when used as a second step treatment in patients with MDD. These results should be confirmed in prospective randomized clinical trials. PMID- 20357665 TI - Cognitive deficits and health-related quality of life in chronic heart failure. AB - BACKGROUND: Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. OBJECTIVES: The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. DESIGN AND SAMPLE: This study was part of a larger explanatory study; 249 patients with HF completed face to-face interviews. METHODS: Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. RESULTS: Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. CONCLUSIONS: Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care. PMID- 20357666 TI - Predictors of complications following sheath removal with percutaneous coronary intervention. AB - BACKGROUND AND RESEARCH OBJECTIVES: Complex antiplatelet and antithrombotic regimens used in conjunction with percutaneous coronary intervention may increase the risk of vascular complications. The purpose of this study was to examine predictors of vascular complications following sheath removal for percutaneous coronary intervention. SUBJECTS AND METHODS: This prospective cohort study enrolled 413 patients during a 7-month period. Data elements were collected by chart abstraction. Practice variable included pharmacological agents and method and duration of sheath removal procedure. Patient outcomes included hematoma formation, bleeding occurrence, pseudoaneurysm prevalence, incidence of arteriovenous fistula formation, and thrombosis. RESULTS AND CONCLUSIONS: Of the 413 patients, 68 (16.5%) had a complication. Sixty-four (15.5%) developed hematomas ranging in size from 1 to 5 cm (n = 35, 8.5%) to greater than 5 cm (n = 29, 7.0%), 6 experienced bleeding (1.5%), 4 (1%) had arteriovenous fistulas, and 3 (0.7%) developed pseudoaneurysms. There were no significant differences for complications using manual, C-clamp, or arterial vascular closure device. Patients with a higher systolic blood pressure (135 vs 129; df = 410, P = .025) and of older age (66 vs 63; df = 411, P = .016) were significantly more likely to have complications. Clinically significant major vascular complications were low. Arterial closure devices, mechanical C-clamp, and manual compression all provide low and comparable complication risks following sheath removal in the era of antiplatelet and antithrombotic therapies. Patients who are older and those with elevated blood pressure should have their femoral access site closely monitored and be observed for vascular complications. PMID- 20357667 TI - Electroconvulsive therapy clinical database: a standardized approach in tertiary care psychiatry. AB - Across health care disciplines research reflects the usefulness of integrating computer technology into administrative and clinical practices. Electroconvulsive therapy (ECT) researchers are often interested in examining 3 primary areas: patient characteristics, treatment characteristics, and treatment outcomes. Generating reports and conducting research analysis via the traditional patient chart review are a time-consuming and costly method. At Riverview Hospital, a tertiary care psychiatric hospital, the active use of a clinical database for patients receiving ECT allows for detailed treatment tracking and evaluation of pretreatment and posttreatment patient outcome measures. Initially, designed as part of a quality improvement process to readily access patient information and generate periodic reports, the ECT clinical database is now a central resource for ECT-specific patient, treatment, and outcome tracking. The relevance, design, content variables, and subsequent functions of the entry and storage of ECT related administrative, treatment, outcome, and patient factors are clearly outlined and discussed. Strengths and limitations to the existing database are shared. Recommendations to other ECT services to implement this valuable documentation strategy are addressed. This approach can be an invaluable tool in providing the field of psychiatry with further contributions to ECT clinical outcomes. PMID- 20357668 TI - Retrospective study of continuation electroconvulsive therapy in 50 patients. AB - OBJECTIVES: To examine patient and treatment characteristics in continuation electroconvulsive therapy (c-ECT), defined as prolonged treatment with ECT with a maximum frequency of once a week to prevent relapse. METHODS: Medical charts of 50 patients (mean age, 59 years; 74% were female) undergoing c-ECT were examined retrospectively for patient and treatment characteristics. Electrical stimulus dosage, seizure duration, and postictal suppression indices between the first and the last 4 ECT sessions were compared, and their associations with the time interval between c-ECT sessions were analyzed. RESULTS: Almost all the patients (n=46; 92%) experienced recurrent medication-resistant mood disorders. During a median c-ECT period of 393 days (interquartile rate, 211-677 days), the frequency of c-ECT ranged from once a week (n=15; 30%) to once every 4 to 6 weeks (n=17; 34%), and ECT was administered almost exclusively bifrontotemporally (n=46, 92%). The mean (SD) time interval between consecutive c-ECT sessions was 19 (11) days. The number of days between c-ECT sessions correlated positively with median seizure duration (motor activity: r=0.390, P=0.005; electroencephalographic activity: r=0.351, P=0.013). CONCLUSIONS: In 50 patients with long-standing, recurrent, medication-resistant mood disorders who were treated with c-ECT, increased time interval between consecutive c-ECT sessions was correlated with increased seizure duration. Whether bifrontotemporal c-ECT requires a lower frequency to sustain remission compared with unilateral c-ECT needs further investigation. PMID- 20357669 TI - Resident education in electroconvulsive therapy. AB - OBJECTIVE: In 2001, the American Psychiatric Association's Task Force on electroconvulsive therapy (ECT) recommended that psychiatry residents should receive at least 4 hours of didactic instruction on ECT, participate in at least 10 treatments, and assist in the care of at least 3 patients receiving ECT. Residency accreditation requirements as of 2007, however, require only that training programs ensure competency in "understanding the indications and uses" of ECT. Anecdotally, training in ECT is said to vary widely between residency programs. The purpose of the study was to obtain more systematic information about ECT training. METHOD: A survey was e-mailed to directors of all accredited psychiatry residency programs in the United States and Puerto Rico in early to mid 2008, requesting information regarding their didactic and clinical instruction in ECT and estimates of number of treatments provided by their institutions. RESULTS: Responses were obtained from 91 training programs. Of these programs, 75% reported that some clinical exposure to ECT was required of their residents, but 37% estimated that the typical resident would participate in fewer than 10 treatments and 27% estimated that the typical resident would care for fewer than 5 patients receiving ECT. Most programs devoted less than 4 hours of lecture time to ECT. Most respondents believed that ECT was underused nationally; this perception did not differ based on the theoretical orientation of the training program. CONCLUSIONS: This study suggests that resident education in ECT varies considerably between programs but is often less than that suggested by the American Psychiatric Association's Task Force. PMID- 20357670 TI - Acoustic neuroma identified after electroconvulsive therapy in a patient with recurrent major depression and undifferentiated somatoform disorder. AB - Little is known about the safety of electroconvulsive therapy (ECT) in patients with brain tumors, especially in patients with acoustic neuroma, which is difficult to diagnose early. For patients with somatoform disorder, physicians may alter the sensitivity to the somatic complaints, making it even more difficult to make an early diagnosis of "silent" brain tumors. This report describes a rare case involving treatment of refractory major depression and somatoform disorder that developed into increased intracranial pressure after ECT, possibly due to an undiagnosed acoustic neuroma. It is suggested that for patients with refractory major depression with somatoform disorders, the threshold of suspicion for silent tumors should be lowered and pre-ECT brain imaging study should be performed, specifically when the pattern of symptoms of the central nervous system-related somatoform syndrome changes. PMID- 20357671 TI - Influence of age on effectiveness and tolerability of electroconvulsive therapy. AB - OBJECTIVES: The effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy-resistant major depressive disorder and schizophrenia has been shown for all age groups. Nevertheless, age-specific adverse effects such as greater cognitive impairment and higher somatic risks due to medical comorbidities and concomitant medication may be limiting factors in geriatric patients. METHODS: We retrospectively evaluated 4457 treatments in 380 patients to investigate the influence of age on ECT outcome, safety, and adverse effects. Clinical variables, treatment modalities, and neurophysiological parameters were analyzed. For modeling the influence of age on these variables of interest, linear and logistic regression models were performed. RESULTS: The mean (SD) age of our patients was 51.2 (15) years; 30% were older than 60 years. Diagnoses were major depressive disorder in 74.4% and schizophrenia in 25.6%. We found a considerable clinical improvement in all age groups. A higher severity of disease at admission corresponded to a better clinical response. Analyzing treatment modalities of elderly patients older than 60 years, no significant differences in need and number of concomitant psychotropic medications were seen, but significant differences were seen in medical co-medication. Ictal and postictal neurophysiological parameters were only in part predictive for clinical outcome, but age had a significant influence on most of them. Transient cardiovascular adverse effects and cognitive disturbances were more frequent in the elderly. In most cases, there was no need for any specific treatment. CONCLUSIONS: Our data confirm previous studies indicating the good effectiveness of ECT irrespective of age. We also found an excellent tolerability profile in the elderly in our patient sample. There was no mortality, and only transient and no life threatening adverse events occurred. PMID- 20357672 TI - Approaching neck pain from in a multidisciplinary perspective: a comprehensive approach to an important public health and societal issue. PMID- 20357673 TI - A survey of injury claims data after introduction of injury care protocols in Alberta, Canada. AB - OBJECTIVE: To monitor the impact of auto insurance regulatory reforms on the no fault injury claims experience of Alberta auto insurers. METHODS: Retrospective file review and abstraction of data from individual auto insurer claim files. RESULTS: Reforms were associated with change in diagnostic frequencies as well as higher health utilization, average cost per treatment episode, cost per claimant, claim closure rate, and reduced incidence of disputes. In spite of these positive indicators, over 40% of claims were still open at 6-month post-injury. CONCLUSIONS: Regulatory reforms in auto insurance systems may affect access to care, health utilization, costs, and outcomes. Stakeholders must continue to monitor the effect of regulatory change on health and insurance practices. PMID- 20357674 TI - Using self-reports of symptom severity to measure and manage workplace depression. AB - OBJECTIVES: To test the workplace impact of depression when it is stratified by severity and considered in broader context. METHODS: Structural equation models of health risk appraisal data (n = 39,097) involving 41 measures of contextual characteristics, depression severity, health, and job performance. RESULTS: Approximately 15.7% exhibited mild depression, whereas 6.9% recorded moderate to severe symptoms. Depression severity exerted large effects on general health and productivity loss, with the mild group posting the largest aggregate impact. Adverse personal life impact and financial concerns more significantly affected moderate to severe depression. In contrast, factors more directly amenable to employer health management efforts (eg, stressful job) better predicted mild depression. CONCLUSIONS: These results link depression to large health and productivity deficits. They call for public-private collaboration, parity in mental and physical health benefits, and resource allocation that is proportionate across the depression spectrum and facilitated by symptom severity screening. PMID- 20357675 TI - The burden of atrial fibrillation and other cardiac arrhythmias in an employed population: associated costs, absences, and objective productivity loss. AB - OBJECTIVE: To establish the burden of atrial fibrillation (AF) and other cardiac arrhythmias (CA) in an employed population. METHODS: Regression model analysis comparing objective work output, employee turnover, comorbidity prevalence, total health benefit (health care, drug, sick leave, disability, workers' compensation) costs, and absence days for AF versus Non-AF and CA versus Non-CA cohorts, while controlling for differences in patient characteristics. RESULTS: Cohort sizes were 1403 (AF), 323,333 (Non-AF), 4497 (CA), and 318,917 (Non-CA) employees. Annual AF benefit costs exceeded Non-AF costs by $3958. CA costs exceeded Non-CA costs by $2897. AF and CA cohorts had significantly more sick leave and short term disability absence days than Non-AF and Non-CA cohorts, respectively. Annual CA work output was significantly lower than Non-CA output. CONCLUSIONS: AF and CA place significant cost, absence, and productivity burdens on employers. PMID- 20357676 TI - The effects of age and shiftwork on perceived sleep problems: results from the VISAT-combined longitudinal and cross-sectional study. AB - OBJECTIVES: With the workforces in industrialized countries getting older, this study sought to determine how shiftworking affects sleep in later life. METHOD: Longitudinal data were collected from a large sample in 1996, 2001, and 2006 from employees who were 32, 42, 52, and 62 years old in 1996. RESULTS: The effects of shift work were most apparent in the early and middle years of working life. Former shiftworkers reported more sleep problems than both current shiftworkers and those who had never worked shifts. Giving up shift work off-set the age related accumulation of sleep problems, with the net result that former shiftworkers showed little or no change in sleep problems over the three measurement occasions. CONCLUSIONS: The effects of shift work on sleep may persist for a long time after giving up shift work but they are not permanent. PMID- 20357677 TI - Neck injuries among electric utility workers, 1995-2007. AB - OBJECTIVE: To describe the incidence and impact of neck injuries among electric utility workers. METHODS: Rates of neck injuries per 10,000 employee-years were calculated for various demographic and occupational factors using data from an injury surveillance database established among 17 electric utility companies over the period 1995-2007. RESULTS: The overall rate of neck injuries was 13.3. Male workers had a slightly higher rate than females, and younger workers (<30) had the highest neck injury rates. Trade/craft workers experienced the highest rates of neck injuries, whereas office-based experienced the lowest. The majority of neck injuries (69%) were sprain/strains and resulted in less than 1 lost day of work (76.7%). CONCLUSIONS: The occurrence of neck injuries in the electric utility workforce varies widely with respect to age, sex, and occupational groups with different characteristics, activities, and work environments. Industry-wide surveillance allows easier identification of injury patterns and risk factors of various injury types and facilitates the development of targeted prevention and intervention strategies to reduce the occurrence of these injuries. PMID- 20357678 TI - Workstyle in office workers: ergonomic and psychological reactivity to work demands. AB - OBJECTIVE: To investigate whether variation in work demands are related to keyboard force, postural change, cognitive reactivity, physiological arousal, and work output in asymptomatic office workers who varied in workstyle. METHODS: Eighty asymptomatic office workers prescreened for level of workstyle (high = 39, low = 41) were enrolled in this study. Participants were exposed to a high- and low-demand work task and biomechanical, physiological, and psychological reactivity were measured. RESULTS: Results indicate that the high workstyle group demonstrated elevated keyboard force (F[1, 74] = 3.99, P < 0.05), greater awkward posture (F[1, 69] = 4.80, P < 0.05), more negative mood changes (F[1, 73] = 10.70, P < 0.01), and more negative work-related cognitions (F[1, 73] = 4.99, P < 0.05). CONCLUSIONS: Asymptomatic office workers with higher levels of self reported adverse workstyle responded to a manipulation of work demands with greater psychological and biomechanical strain. PMID- 20357680 TI - An estimate of cancers attributable to occupational exposures in France. AB - OBJECTIVE: To perform a quantitative estimate of the proportion of cancers attributable to occupational exposures in France in 2000. METHODS: Exposure data for established carcinogens were obtained from a 1994 survey and other sources. Relative risks for 23 exposure-cancer combinations were derived from meta analyses and pooled analyses. RESULTS: A total of 4335 cases of cancer among men (2.7% of all cancers) and 403 cases among women (0.3% of all cancers) were attributed to occupational exposures. Asbestos, polycyclic aromatic hydrocarbons, and chromium VI were the main occupational carcinogens in men, and asbestos and involuntary smoking were the main carcinogens in women. Corresponding proportions for cancer deaths were 4.0% and 0.6% in men and women, respectively. Lung cancer represented 75% of deaths attributable to occupational exposures. CONCLUSION: Our estimates are comparable with those obtained for other countries in studies based on similar methodology. PMID- 20357679 TI - Evaluation of cumulative lead dose and longitudinal changes in structural magnetic resonance imaging in former organolead workers. AB - OBJECTIVE: : We evaluated whether tibia lead was associated with longitudinal change in brain volumes and white matter lesions in male former lead workers and population-based controls in whom we have previously reported on the cognitive and structural consequences of cumulative lead dose. METHODS: : We used linear regression to identify predictors of change in brain volumes and white matter lesion grade scores, using two magnetic resonance imaging scans an average of 5 years apart. RESULTS: : On average, total brain volume declined almost 30 cm, predominantly in gray matter. Increasing age at the first magnetic resonance imaging was strongly associated with larger declines in volumes and greater increases in white matter lesion scores. Tibia lead was not associated with change in brain volumes or white matter lesion scores. CONCLUSIONS: : In former lead workers in whom cumulative lead dose was associated with progressive declines in cognitive function decades after occupational exposure had ended, cumulative lead dose was associated with earlier persistent effects on brain structure but not with additional worsening during 5 years. PMID- 20357681 TI - Illness-associated productivity costs among women with employer-sponsored insurance and newly diagnosed breast cancer. AB - OBJECTIVE: Determine lost work time and job attrition for incident breast cancer (BC). METHODS: The cases were employed women, aged 18 to 64, with BC identified by a validated algorithm between 1999 and 2005, from claims (MarketScan) and attendance databases. Controls without cancer were matched 3:1 on age, comorbidity, and index year. RESULTS: First-year mean disability days were 60 (cases, N = 880) versus 5 (controls, N = 2640) (P < 0.001). The first-year disability costs were $4900 for cases versus $385 for controls (P < 0.001). In years 2 through 4, the disability days and associated costs were similar for the cases versus controls. After 4 years, 56.4% of cases were still enrolled in the employer-sponsored insurance programs compared to 6.5% of controls (P < 0.001). CONCLUSIONS: The lost work associated with BC is substantial in the first year after diagnosis. Employee retention is much higher for BC cases versus controls. PMID- 20357682 TI - Findings from the bone and joint decade 2000 to 2010 task force on neck pain and its associated disorders. AB - OBJECTIVE: To summarize the key findings of a best-evidence synthesis on neck pain. METHODS: A systematic search, critical review, and best-evidence synthesis of the literature on the burden and determinants of neck pain, its assessment and intervention, and its course and prognostic factors. RESULTS: There were 552 studies judged to have adequate internal validity to form the basis of the best evidence synthesis. Neck pain is common across populations and age groups. Most do not experience a complete resolution of symptoms, and its course of recovery is similar across populations. In the absence of trauma and "red flags," routine imaging is not needed. Treatments emphasizing activity and return to normal function are more beneficial than those without such a focus. CONCLUSION: Neck pain is common, and its determinants and prognosis are multifactorial. PMID- 20357683 TI - Epidemiology in the courtroom: an evidence-based paradigm for the determination of causation in compensation environments. AB - OBJECTIVE: Identify an evidence-based paradigm for the determination of causation of occupational injury and illness litigation. METHODS: The Westlaw and LexisNexis databases were used to identify legal principles governing the admissibility of scientific evidence in legal proceedings. The Medline database was referenced to identify evidence-based methods for the determination of causation complying with legal precepts for the admissibility of scientific testimony. RESULTS: Expert witness testimony must be relevant and reliable. Testimony must be sufficiently based on reliable facts and data. Testimony must be the product of reliable principles or methods. The witness must have reliably applied the principles and methods to the facts of the case. CONCLUSIONS: Conscientious application of the National Institute for Occupational Safety and Health Guide for the Determination of Work-Relatedness of Disease, as adapted, comforts with legal prerequisites for the admissibility of scientific evidence in medicolegal proceedings. PMID- 20357684 TI - Whiplash injury is more than neck pain: a population-based study of pain localization after traffic injury. AB - OBJECTIVES: To describe the distribution of bodily pain and identify common patterns of pain localization after traffic injury. METHODS: Cross-sectional analysis of a population-based cohort of 6481 Saskatchewan residents who were treated or filed an auto insurance claim within 30 days of traffic injury or both. The prevalence of pain in each of 13 body areas was calculated and compared with pain confined exclusively to each of these areas. Principal component analysis was used to identify the main patterns of pain localization after traffic injury. RESULTS: Irrespective of pain in other areas, 86% of respondents reported posterior neck pain, 72% indicated head pain, and 60% noted lumbar back pain. Ninety-five percent of claimants reported some pain within the posterior trunk region, comprising the posterior neck, shoulder, mid-back, lumbar, and buttock areas. Only 0.4% of respondents reported posterior neck pain only. Four main patterns accounted for 60% of the variance in pain localization: 1) upper anterior trunk and upper extremity pain; 2) head, posterior neck, and upper posterior trunk pain; 3) low back pain; and 4) lower anterior trunk and lower extremity pain. CONCLUSION: Pain after traffic injury is most commonly reported in multiple body areas; isolated neck pain is extremely rare. These results have implications for clinical management of traffic injuries and interpretation of whiplash-related trials. PMID- 20357685 TI - Preventing minor neck injuries in rear crashes--forty years of progress. AB - OBJECTIVE: This article offers a historical review of vehicle design measures that have been implemented to reduce the risk of neck injuries to the occupants of rear struck vehicles. METHODS: The literature on regulations, consumer information programs, and efforts by vehicle manufacturers to address whiplash injuries is summarized along with studies evaluating the efficacy of the resulting vehicle design changes. RESULTS: Vehicle designs and, in particular, the designs of seats and head restraints have changed considerably over the last 40 years. With varying degrees, these changes seem to be reducing the likelihood that occupants in rear struck vehicles will suffer neck injuries in such crashes. CONCLUSIONS: Vehicle design has influenced the risk of neck injuries in crashes, and future design changes offer potential for further risk reduction. PMID- 20357686 TI - Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma. AB - The aim of this study was to analyze microphthalmia-associated transcription factor (MITF) as a marker for the detection of circulating melanoma cells, determine its prognostic value in melanoma patients, and compare it with tyrosinase. Blood samples from 201 melanoma patients in all stages of the disease and 40 healthy volunteers were analyzed. RNA was isolated from mononuclear cell fraction of the blood and assayed by reverse transcription-PCR for the expression of MITF and tyrosinase. All samples from healthy volunteers were negative for both MITF and tyrosinase. Out of 201 blood samples from melanoma patients 32 were positive for MITF, 20 for tyrosinase, and four for both MITF and tyrosinase. Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive). A positive value of MITF was associated with shorter progression-free (P=0.005) and overall survival (P=0.042). A positive value of tyrosinase was associated with shorter overall survival (P=0.012), whereas there was no significant association between the value of tyrosinase and progression-free survival. The value of MITF was selected with multivariate analysis as the independent prognostic factor for progression free survival, whereas the only independent prognostic factor for overall survival was the stage of disease. This study has shown that MITF is a specific marker for detection of circulating melanoma cells that has a prognostic value in melanoma patients. Determination of MITF in addition to tyrosinase improved the detection of circulating melanoma cells in melanoma patients. PMID- 20357687 TI - Impact of walking on eating behaviors and quality of life of premenopausal and early postmenopausal obese women. AB - OBJECTIVE: Aerobic exercise is known to improve health-related quality of life (QoL). The aim of this study was to compare the effects of a 16-week walking program on eating behaviors and QoL between late premenopausal and early postmenopausal obese and sedentary women, once chronological aging is taken into account. METHODS: Sixteen women 49 +/- 2 years old and 14 women 53 +/- 2 years old, whose body mass index ranged between 29 and 35 kg/m, were subjected to three sessions per week of 45-minute walking at 60% of their heart rate reserve. Fat mass and lean mass (bioelectrical impedance), cardiorespiratory fitness estimated by maximum oxygen consumption (2-km walking test), eating behaviors (Three-Factor Eating Questionnaire), and QoL, estimated by the Short Form-36 Health Survey, Pittsburgh Sleep Quality Index, and Perceived Stress Scale-10 questionnaires, were recorded before and after exercise. RESULTS: With the exception of a higher attitude of self-regulation in postmenopausal than in premenopausal women (P = 0.05), no between-group differences were observed in body composition, eating behaviors, and QoL at baseline. In all participants, body weight and fat mass decreased, whereas cardiorespiratory fitness increased after walking (0.001 < P < 0.0001). Situational susceptibility was the only eating behavior reduced after training in all women (P = 0.02). Neither the sleep quality index nor the perceived stress score changed in response to endurance exercise. Finally, in all women, Short Form-36 physical and mental scores increased after walking (0.001 < P < 0.05). CONCLUSIONS: Despite modest body weight and fat mass losses, a 16-week walking program seems to be sufficient to improve physical and mental well-being, irrespective of menopause status. PMID- 20357688 TI - Human orbitofrontal-striatum functional connectivity modulates behavioral persistence. AB - The degree at which individuals maintain behavioral strategies during uncertain conditions varies widely; however, the neural bases of these individual differences remain unclear. This study examines the functional connectivity of the orbitofrontal cortex during a decision-making task using functional magnetic resonance imaging. The strength of the functional connectivity observed between the medial orbitofrontal cortex and the nucleus accumbens was determined to be correlated with the number of persistent responses made during the decision making task. It is proposed that top-down control of the orbitofrontal cortex over the ventral striatum is a critical component underlying individual differences in decision making during uncertain conditions. PMID- 20357689 TI - Influence of global motion onset on goal-directed eye movements. AB - Saccades are very rapid eye movements in between two phases of fixation, which offer a precise measure of behaviour for the direction of the spotlight of attention. The onset of global motion is known to attract our attention reflexively. We asked whether brief global motion stimuli are able to modify the execution of saccades. When participants performed visually guided saccades towards a target presented in front of a structured background, saccade latency was 174 ms on average and correctness of saccades was 100%. If the presentation of the target occurred at the same time as the onset of a brief global motion signal, then the saccade latency increased dramatically to 243 ms with a slight decrease in correctness to 89%. However, if the motion stimulus preceded the presentation of the target, then the latency decreased to 114 ms while the correctness dropped close to chance levels (62%). PMID- 20357690 TI - Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics. AB - OBJECTIVES: This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism 31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer. METHODS: Eighty patients with pancreatic cancer and 160 healthy controls were investigated for genotype and allelic frequencies of caspase-9 1263A/G and survivin -31G/C polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. RESULTS: The G carrier group of patients and the G allele of caspase-9 1263A/G were overrepresented among the pancreatic cancer cases. With regard to tumor characteristics, a statistically significant association was detected between the survivin C carrier group of patients and the advanced T stage as well as the presence of lymph node metastasis. CONCLUSIONS: The caspase 9 G allele confers increased susceptibility to pancreatic cancer development, and the survivin C carriage status may be related to aggressive features of this malignancy. PMID- 20357691 TI - MUC1 is a useful molecular marker for malignant intraductal papillary mucinous neoplasms in pancreatic juice obtained from endoscopic retrograde pancreatography. AB - OBJECTIVES: Some intraductal papillary mucinous neoplasms (IPMNs) have no proliferation to malignant IPMNs, and benign IPMNs can observe the natural course without a surgical intervention. Therefore, an accurate assessment is required to determine the appropriate decision on managing malignant IPMNs. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction was performed for pancreatic juice by a LightCycler instrument focused on carcinoembryonic antigen, MUC1, and human telomerase reverse transcriptase. RESULTS: MUC1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) ratio in intraductal papillary mucinous carcinoma (IPMC; median, 4710.7) was significantly higher in intraductal papillary mucinous adenoma (IPMA; median, 727; P = 0.0229). Furthermore, the MUC1/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in carcinoma in situ and minimum invasive IPMC (median, 26,490) was significantly higher than that in IPMA (P = 0.0152). The cutoff level of MUC1 ratio was determined as 1600 for the division of IPMC from IPMA by the receiver operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MUC1 mRNA were 88.9%, 71.4%, 80.0%, 83.3%, and 81.3%, respectively. CONCLUSIONS: Quantitative reverse transcription-polymerase chain reaction using MUC1 is useful for the detection of malignant IPMN in pure pancreatic juice. PMID- 20357693 TI - Early mannan detection in bronchoalveolar lavage fluid with preemptive treatment reduces the incidence of invasive Candida infections in preterm infants. AB - BACKGROUND: Candida colonization is an important predictor for development of invasive fungal infection (IFI). We investigated whether early detection of Candida mannan (Mn) in bronchoalveolar lavage fluid (BALF) reduces IFI among preterm infants. METHODS: We conducted an observational study of infants with gestational age of < or =28 weeks, where a group undergoing Candida surveillance cultures (pre-Mn detection group) was compared with a group defined after the initiation of routine use of Candida Mn detection in BALF (Mn detection group). Antifungal treatment was started based on positive microbiologic (surveillance culture or Mn-antigen assay) results. RESULTS: No significant differences were detected when the groups were compared for several predictors of IFI. IFI was observed for 12 (23%) of 51 infants in the pre-Mn detection group, and for 0 (0%) of 29 infants in the Mn detection group (P = 0.003). Surveillance cultures in the pre-Mn detection group became positive at 15.0 +/- 7.2 days after birth, whereas the mean age at time of positive Mn antigen results in the Mn detection group was 4.3 +/- 3.1 days (P < 0.0001). Among 16 infants positive for surveillance cultures, 12 (75%) developed IFI (P < 0.0001). CONCLUSIONS: This study suggests that Candida Mn detection in BALF may be useful for earlier identification and preemptive therapy targeting preterm infants at high risk of IFI. PMID- 20357692 TI - Optimal timing of oral refeeding in mild acute pancreatitis: results of an open randomized multicenter trial. AB - OBJECTIVES: The aim of this study was to compare 2 protocols regarding the initiation of oral nutrition in patients with mild acute pancreatitis. METHODS: We randomized 143 patients to the Lipase directed (LIP) (n = 74) and the self selected PAT (n = 69) group. In the (PAT) group, the patients restarted eating through self-selection. In the LIP group, serum lipase had to normalize before eating. RESULTS: The mean time between admission and oral nutrition was 2 days (interquartile range [IQR], 1-3) in the PAT group and 3 days (IQR, 2-4) in the LIP group (P < 0.005). Before and after the first meal, the mean Delta visual analogue scale (VAS) was +3.14 mm (+/-11.5 mm) in the PAT group and +2.85 mm (+/ 16.4) in the LIP group (P = 0.597). The length of hospital stay was 7 days (median; IQR, 5-10.5) in the PAT group and 8 days (median; IQR, 5.75-12) in the LIP group (P = 0.315). CONCLUSIONS: We were not able to demonstrate a difference in postprandial abdominal pain or in the length of hospital stay. Patients with self-selected eating, however, were able to restart eating 1 day earlier, and this difference was found to be significant. Our data suggest that normalization of serum lipase is not obligatory for enteral nutrition in mild acute pancreatitis. PMID- 20357694 TI - Effect of subcutaneous fat on quantitative bone ultrasound in chicken and neonates. AB - Bone quantitative ultrasound generated speed of sound (SOS) is a marker of bone strength. However, critical evaluation of its validity for use in small bones is extremely limited, and SOS data may not be consistent with data obtained from dual energy x ray absorptiometry, another marker of bone strength. We report the SOS values pre and postinjection of s.c. fat using a chicken bone model; and in large for gestation and appropriate for gestation neonates to determine the influence of s.c. fat. Average SOS were lowered for the chicken bones postfat injection by 36 m/s (CS probe) and 58 m/s (CR probe), and in large for gestation group by 75 m/s (CS probe) and 51 m/s (CR probe) (p = 0.03-0.004 paired t test) although SOS measurements from each probe are significantly correlated within the large (r = 0.78) and appropriate (r = 0.83) for gestation group. Failed SOS measurements occurred significantly more frequently in the postinjection studies regardless of the probe used in the chicken bone model and for the CS probe in large for gestation neonates. The lowered bone quantitative ultrasound measurements in large for gestation neonates is likely a measurement artifact from increased s.c. fat. PMID- 20357695 TI - 2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease. AB - 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) is a promising experimental therapy for Niemann-Pick type C disease that improved intracellular cholesterol transport, substantially reduced neurodegeneration and hepatic disease, and increased lifespan in npc1 mice. On the basis of favorable treatment outcome in mice, HPbetaCD is being evaluated as a therapy in children with Niemann-Pick type C (NPC) disease. We evaluated the efficacy of HPbetaCD in the feline model of NPC disease and recognized a dose-dependent increase in hearing threshold associated with therapy as determined by brain stem auditory evoked response (BAER) testing. To further assess the effect of HPbetaCD on hearing threshold, normal cats were administered the drug s.c. at either 4000 mg/kg or 8000 mg/kg body weight, or intrathecally at a dose of 4000 mg/kg brain weight. HPbetaCD caused a significant increase in hearing threshold following one dose of 8000 mg/kg s.c. or 120 mg intrathecally, and the effect was maintained for at least 12 weeks. Repeated weekly s.c. administration of 4000 mg/kg HPbetaCD resulted in a similar increase in hearing threshold. These studies are the first to describe a specific negative effect of HPbetaCD on the auditory system and suggest the need for auditory testing in patients receiving similar doses of HPbetaCD. PMID- 20357696 TI - Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension. AB - Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 +/- 2 mmHg (mean +/- SD) to 31 +/- 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 +/- 14 mmHg to 27 +/- 13 mmHg (mean +/ SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% +/- 21%, 69% +/- 20%, 76% +/- 16%, 79% +/- 18%, and 81% +/- 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% +/- 19%, 77% +/- 13%, 66% +/- 26%, and 71% +/- 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows. PMID- 20357698 TI - Genetic variations in ABCB1 and CYP3A5 as well as sex influence quinine disposition among Ugandans. AB - Quinine is one of the most effective antimalarial drugs, although its clinical use is limited as a result of its narrow safety margin. Quinine is a substrate of the polymorphic p-glycoprotein and CYP3A4/3A5. This study aimed to examine the effects of genetic variations in ABCB1 and CYP3A5 genes, sex, demographic, and biochemical variables (serum albumin, creatinine, alanine aminotransferase and albumin) on quinine disposition among Ugandans. Quinine (600 mg) was orally administered to 140 healthy volunteers. Quinine and its metabolite 3 hydroxyquinine concentrations were determined from 16-hour postdose plasma by high-performance liquid chromatography. CYP3A5 activity was measured using quinine/3-hydroxyquinine ratio (metabolic ratio). Genotyping for a total of 20 single nucleotide polymorphisms in ABCB1 (n = 13) and CYP3A5 (n = 7) was done using Taqman and minisequencing on microarray. There were 20.5- and 13-fold variations in body weight-adjusted plasma quinine concentrations (mean +/- standard deviation, 5.26 +/- 2.5 mumol/L; range, 0.88-18.10 mumol/L) and quinine to-3-hydroxyquinine metabolic ratio (mean +/- standard deviation, 7.68 +/- 3.3 mumol/L; range, 1.66-22.3 mumol/L), respectively. Weight-adjusted plasma quinine concentration was significantly influenced by sex and ABCB1 haplotype. There was a significant sex difference in quinine metabolic ratio, women being faster metabolizers than men (P = 0.01). CYP3A5 genotype/haplotype significantly (P = 0.03) influenced quinine disposition with a clear CYP3A5*1 gene dose effect. The result confirms that quinine disposition is influenced mainly by sex as well as by ABCB1 and CYP3A5 genotypes. Despite being fast metabolizers, women display higher quinine bioavailability than men in Uganda. This may have clinical significance in determining an individual's susceptibility to quinine-associated adverse reactions such as cinchonism. PMID- 20357697 TI - The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model. AB - Sepsis is often associated with cholestatic liver dysfunction caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models, the role of ischemic hepatitis caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. Fifteen anesthetized and instrumented pigs were randomized to either fecal peritonitis (n = 8) or control (n = 7). Resuscitation was performed by hydroxyethyl starch and norepinephrine infusion. Hemodynamic parameters and markers of cholestatic and ischemic hepatic dysfunction were recorded. At baseline and after 21 h, messenger RNA (mRNA) and protein expression of bile salt transporters was determined by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, on in vivo liver biopsies. All resuscitated septic pigs developed a normotensive hyperdynamic circulation with increased portal flow. After 21 h of peritonitis, no signs of biochemical or histological cholestasis were present. Na-taurocholate cotransporting polypeptide and bile salt export pump mRNA were downregulated by 83% (P = 0.001) and 67% (P = 0.001), respectively, in comparison with controls, whereas multidrug resistance associated protein 4 (MRP4) mRNA was upregulated by 85% (P = 0.02). Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids. PMID- 20357699 TI - Pharmacokinetics of mycophenolic acid and its glucuronidated metabolites in stable islet transplant recipients. AB - Given the paucity of data on pharmacokinetics of mycophenolic acid (MPA) in islet transplant, the aim of this study was to characterize pharmacokinetic parameters of MPA and its 2 glucuronidated metabolites in stable islet transplant recipients. Sixteen subjects were entered into this open-label study after written informed consent. Upon administration of a steady-state morning mycophenolate mofetil dose, 12-hour serial concentrations of MPA and its phenolic glucuronide (MPAG) and acyl-glucuronide (AcMPAG) were measured by a validated high-performance liquid chromatography method and pharmacokinetic parameters analyzed by noncompartmental modeling. Subjects included 11 women and 5 men who had received 2.7 +/- 0.8 islet transplants. Age was 50 +/- 8 years, weight 64 +/- 11 kg, serum albumin 4.2 +/- 0.3 g/dL, and serum creatinine 1.1 +/- 0.4 mg/dL. All patients were also on tacrolimus-based steroid-free immunosuppressant regimens. Mycophenolate mofetil dosage ranged from 1 to 2 g daily (25.4 +/- 6.1 mg/kg/d). Pharmacokinetic parameters for MPA were area under the curve 42.9 +/- 21.6 microg h/mL; dose-normalized AUC 52.9 +/- 25.4 microg h/mL/g; maximal concentration (Cmax) 13.0 +/- 6.2 microg/mL; time to Cmax (tmax) 1.2 +/- 0.4 hours; minimum concentration (Cmin) 1.4 +/- 1.0 microg/mL; and MPA-free fraction 1.2% +/- 1.0%. Area under the curve ratios of MPAG/MPA and AcMPAG/MPA were 17.8 +/- 12.4 and 0.1 +/- 0.1, respectively. The wide interpatient variability in all pharmacokinetic parameters of MPA and metabolites are consistent with results from the only other published pharmacokinetic study in islet transplant recipients. A population model and a search for significant covariates may help reduce this variability. Pharmacokinetic parameters calculated in the present study, coupled with findings from the only other published MPA study in islet transplant, form a preliminary base on which to build a population model for future multicenter studies of this little-studied transplant subpopulation. PMID- 20357701 TI - Using the media to promote palliative care. PMID- 20357702 TI - Improving palliative care for people with long-term neurological conditions. PMID- 20357700 TI - Prolactin supplementation to culture medium improves beta-cell survival. AB - OBJECTIVES: Recent studies demonstrated that prolactin (PRL) has beneficial effects on beta cells for islet transplantation. We examined the effect of human recombinant PRL (rhPRL) supplementation to the culture media to determine its potential use in the context of clinical islet transplantation. MATERIALS AND METHODS: Each human islet isolated from 14 deceased multiorgan donors was cultured in Miami modified media-1 supplemented with or without rhPRL (500 microg/L) for 48 hr. beta-Cell survival and proliferation (BrdU and Ki-67) were determined by laser scanning cytometry. The cytoprotective effects of rhPRL against noxious stimuli were assessed by flow cytometry (tetramethylrhodamine ethyl ester). Cytokine/chemokine and tissue factor productions were measured in vitro, and islet potency was assessed in vivo in diabetic immunodeficient mice. RESULTS: beta-Cell survival during culture was 37% higher in the rhPRL group than in control (P=0.029). rhPRL protected beta cells in vitro from cytokines, Nitric oxide donor, and H2O2. The exposure to rhPRL did not affect human beta-cell proliferation with our protocol. rhPRL treatment did not alter cytokine/chemokine and tissue factor production in vitro or affected human islet functionality in vivo: recipient mice achieved normoglycemia with a comparable tempo, whereas loss of graft function was observed in two of the seven mice in the control group and in none of the rhPRL group (p=n.s.). CONCLUSION: rhPRL supplementation to islet culture media improved human beta-cell-specific survival without altering islet quality. Addition of rhPRL to cultured islets may grant a more viable beta-cell mass in culture. The development of beta-cell cytoprotective strategies will be of assistance in improving islet transplantation outcomes. PMID- 20357703 TI - Learning to live with childhood cancer: a literature review of the parental perspective. AB - This article presents an analysis of literature on paternal and maternal development and resilience through the experience of having a child diagnosed, treated, and possibly die from cancer. The methods and analysis of findings from research conducted in this area are assessed, as are the data's relevance and implications for practice. The review required an in-depth search of relevant health-care databases using appropriate search terms. Findings were then culled and analysed based on the inclusion and exclusion criteria, and two papers were deemed appropriate for selection. Four contrasting themes emerged from each article. It was generally acknowledged that mothers and fathers enduring such an experience stated that changes occurred in their lives. The mothers felt a need to become tougher for their child and family, and the fathers recognized a need to focus quickly on what needed to be done to treat their child's illness. However, analytically the differences in each paper are vast. The research was conducted in Japan and the United States, where contrasting cultural and societal beliefs and influences are apparent, therefore inadvertently affecting the research findings. Furthermore, a gap in research in this area has been detected, and much more research specifically focused on this subject is required if the children's nurse is to provide evidence-based holistic care in this area on a continual basis. PMID- 20357704 TI - Collaborative working in end-of-life care: developing a guide for health and social care professionals. AB - This article describes a project to develop collaborative working between palliative care nurse specialists and community matrons for patients with a non cancer diagnosis. Pathways to clarify decision-making in end-of-life care were created as part of the project and were subsequently developed into a guide for use by health or social care professionals caring for any patient, irrespective of diagnosis. The guide is designed to facilitate best practice in end-of-life care, by identifying the key questions which need to be addressed and the appropriate responses at different stages of the patient journey. The project was supported by the Help the Hospices' Care Beyond Cancer programme, funded by the St James's Place Foundation. The programme is designed to identify models of effective, replicable end-of-life care provision for patients with a non-cancer diagnosis, and to widen access to specialist palliative care. PMID- 20357705 TI - Using syringe drivers in palliative care within a rural, community setting: capturing the whole experience. AB - The aim of this research was to understand how the introduction of a syringe driver, which is considered routine practice in many palliative care settings, impacted on patients, carers and community nurses within a rural, community setting. A phenomenological study was conducted exploring the experiences from the perspective of patients (n=4), carers (n=9) and community nurses (n=12) when syringe drivers are used at home. We interviewed patients and carers in their own homes and conducted two focus groups with community nurses who had an interest in palliative care but were not specialists. Despite the wide use of syringe drivers within palliative care, our study found their use among community nurses, particularly in rural areas can be variable with frequent time lapses between a nurse's exposure, impacting on both their technical abilities and knowledge. In depth interviews with patients revealed few barriers to their use, but carers clearly identified areas where their expectations and experiences differed and where more information setting realistic goals of care would have been helpful. The authors conclude that although nurses require competencies related to syringe drivers, they also need an in-depth knowledge of the actions of the drugs and the likely changes which occur physiologically as patients approach the end of their life. This will ensure accurate information is delivered, and facilitate meaningful dialogue. PMID- 20357706 TI - Establishing the validity of a spiritual distress scale for cancer patients hospitalized in southern Taiwan. AB - The present study was conducted to establish the validity of the spiritual distress scale (SDS), a scale developed as part of a qualitative study in which 20 cancer patients were interviewed about spiritual needs in 2003-2004. The SDS has four domains: relationship with self, relationship with others, relationship with God, and attitude towards death A measurement study was conducted whereby 85 patients completed the SDS during their hospitalization in the oncology unit of a medical centre in southern Taiwan. The SDS, including four domains of sub-scales, was broader than other spiritual scales in the literature that only contained one or two domains and focused on the health area. The SDS has established the adequate content and construct validity. Further training of nurses for assessing spiritual distress of cancer patients using the SDS would be recommended for future study. The established content and construct validity of the SDS could be applied in oncology for nurses to assess spiritual distress of cancer patients. PMID- 20357707 TI - Community nurses' perceptions of a good death: a qualitative exploratory study. AB - AIMS: This study sought to gain an insight into perceptions of a 'good death' among community nurses, and to identify its central components. By understanding these factors, it was hoped that common difficulties could be identified, enabling recommendations to be made to enhance patient care and reduce the pressures to which nurses are exposed. METHOD AND SAMPLE: This qualitative exploratory study relied on semi-structured interviews, incorporating the critical incident technique to elicit retrospective accounts of experiences of palliative care and a good death. Data was obtained from a purposive sample of 17 community nurses, working in a single primary care trust in south-east England. RESULTS: The participants identified eight key themes in supporting a good death: symptom control, patient choice, honesty, spirituality, interprofessional relationships, effective preparation and organization and provision of seamless care. When these are in place, a good death is possible. Factors such as lack of necessary medication/resources, unsuccessful interprofessional relationships and lack of teamwork were significant determinants of less successful care. The provision of seamless care was an important criterion for success. CONCLUSIONS: In identifying the contributory factors, this study has shown that a good death can be provided in the community, although it has also revealed many challenges associated with such care. While it could be argued that due to the unpredictability of death, such challenges may always be a threat to effective care anticipatory planning and a recognition that patients need and are entitled to specialist care many of these difficulties could be overcome. PMID- 20357710 TI - Vanadate affects proliferation of healing fibroblasts, cellular production of collagen, and expression of alpha-SMA in vitro. AB - BACKGROUND: The medial collateral ligament of the knee is frequently injured in sports. The medial collateral ligament healing is slow. Vanadate is a transition element that has been shown to be a nonspecific inhibitor of protein tyrosine phosphatases. It has notable effects on wound healing. This study sought to examine the effect of vanadate on proliferation, collagen type I, and alpha smooth muscle actin (alpha-SMA) production in healing fibroblasts in rat (Sprague Dawley). MATERIAL/METHODS: Fibroblasts were obtained from a healing medial collateral ligament. Cell cultures were treated with different concentrations of vanadate (5, 10, 20 micromol/L). Healing fibroblasts without vanadate treatment were used control group. Fibroblast proliferation was measured using a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Production of collagen type I in a supernatant culture was assayed by enzyme-linked immunosorbent assay (ELISA). Expression of alpha-SMA was assessed by Western blot. RESULTS: At concentrations of 5 micromol/L, 10 micromol/L, 20 micromol/L of vanadate, fibroblast proliferation was significantly increased. Treatment with vanadate significantly increased the production of collagen type I and decreased a-SMA expression in healing fibroblasts in a dose-dependent manner. CONCLUSIONS: Our results showed that vanadate therapy improves ligament repair via increase in proliferation and collagen type I production, and a decrease in alpha-SMA expression in healing fibroblasts. The results provide a cellular and molecular basis for vanadate's action as a therapeutic agent for enhancing medial collateral ligament healing and reducing scar formation. PMID- 20357711 TI - Fasudil attenuates lipopolysaccharide-induced acute lung injury in mice through the Rho/Rho kinase pathway. AB - BACKGROUND: The transendothelial migration of polymorphonuclear leukocytes (PMNs, neutrophils) may be a hallmark of acute lung injury (ALI). The breakdown of the vascular endothelial barrier has likewise been considered to have etiologic linkage in the pathogenesis of ALI. Rho-associated coiled-coil-forming protein kinase (ROCK), a downstream target effector of the small GTP-binding protein Rho, plays a key role in cell adhesion, motility, and contraction mediated by reorganization of the actin cytoskeleton. The aims were to investigate protection by fasudil in lipopolysaccharide (LPS)-induced ALI and the role of ROCK2 in neutrophil transendothelial migration in a murine model. MATERIAL/METHODS: Mice were assigned to three groups: sham-treated controls (Sham group), LPS instillation (LPS group), and protective application of fasudil and LPS instillation (Fasudil/LPS group). Indexes tested were breathing frequency, histopathological examination, lung injury score, lung wet-to-dry weight ratio, neutrophil percentage in bronchoalveolar lavage fluid (BALF), myeloperoxidase activity, and ROCK2 mRNA expression in lung homogenate. RESULTS: Permeability pulmonary edema (histopathological examination, lung injury score, and lung wet to-dry weight ratio) was ameliorated and neutrophil infiltration in the lungs (neutrophil percentage in BALF, myeloperoxidase activity) was depressed in response to fasudil administration. Expression of ROCK2 mRNA in the lung homogenates of the LPS-treated mice increased approximately fourfold; however, fasudil did not affect the increase. CONCLUSIONS: The Rho/Rho kinase pathway may play an important role in the pathogenesis of LPS-induced ALI and fasudil, as a ROCK inhibitor, could decrease neutrophil transendothelial migration by attenuating cytoskeletal rearrangement of endothelial cells, leading to the inhibition of ALI development. PMID- 20357712 TI - The supratrochlear foramen of the humerus and its relation to the medullary canal: a potential surgical application. AB - BACKGROUND: The supratrochlear foramen of the humerus is located at the septum separating the coronoid from the olecranon fossa. Beyond its anthropologic interest, that trait seems to have clinical significance as well. MATERIAL/METHODS: The supratrochlear foramen was studied in 240 macerated adult humeri. The foramen was recorded in each sex and each side. We attempted to enlighten the likely relation of the foramen with the inferior edge of the medullary canal, as well as that of the dimensions of that canal of humerus and compare it to contralateral humeri without foramen. RESULTS: The medullary canal width at the entry point of a retrograde intramedullary nail was statistically smaller in humeri with foramen than in humeri without it. Furthermore, the medullary canal of the humeri with foramen ends more proximally than the canal of nonforamen humeri. CONCLUSIONS: In cases of humeral fractures of the supratrochlear foramen, the surgeon must keep in mind that it is better to perform an antegrade medullary nailing than a retrograde one; as there is higher chance of a secondary fracture, due to the extreme narrowness of the canal at the distal portion of humeri with the supratrochlear foramen. PMID- 20357713 TI - Effects of acute verjuice consumption with a high-cholesterol diet on some biochemical risk factors of atherosclerosis in rabbits. AB - BACKGROUND: Metabolic changes in postprandial state particularly after fatty meals lead to atherosclerosis progression. Verjuice is an acidic juice made from unripe grape, commonly used as a popular ingredient in Iran. In this study the acute effects of verjuice intake on postprandial values of some biochemical atherosclerosis risk factors in rabbits fed high-cholesterol diets were investigated to see if it has is a possible protective role. MATERIAL/METHODS: Rabbits were allowed free access to diets containing: no cholesterol, 1% cholesterol, 1% cholesterol with 5 ml of verjuice, and 1% cholesterol with 10 ml of verjuice. C-reactive protein (CRP), malondialdehyde (MDA), nitrite, nitrate, glucose, LDL-cholesterol (LDL-C), oxidized-LDL (ox-LDL), total cholesterol (TC), apolipoprotein B (ApoB), triglyceride (TG), HDL-cholesterol (HDL-C), apolipoprotein A(ApoA), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT), and fibrinogen levels were measured before and three hours after feeding these diets. RESULTS: Significant differences were observed in fibrinogen and glucose levels between the high cholesterol diet with 5 and 10 ml verjuice and the high-cholesterol diet alone. Using 10 ml verjuice with the the high-cholesterol diet caused a significant reduction in ox-LDL, MDA, and nitrite compared with the high-cholesterol diet alone. No significant difference was found between the groups receiving verjuice and the high-cholesterol diet group in TC, HDL-C, TG, LDL-C, ApoA, ApoB, SGPT, SGOT, nitrate, or CRP. CONCLUSIONS: These results suggest that there might be an acute protective effect in the postprandial use of verjuice on some of the risk factors of atherosclerosis, particularly as an antioxidant. PMID- 20357714 TI - Gene polymorphism of epidermal growth factor receptor and airway hyperresponsiveness in young allergic subjects without respiratory symptoms. AB - BACKGROUND: Airway hyperresponsiveness (AHR) in young asymptomatic adults with atopy can be one of indicators of future symptomatic asthma. We aimed to investigate genetic association of epidermal growth factor receptor (EGFR) with the asymptomatic AHR. MATERIAL/METHODS: We recruited one-hundred and eighty-nine allergic volunteers (mean age 19.5+/-1.4 y.o.) without history of respiratory symptoms, measured bronchial responsiveness to methacholine (0.3 to 10.0 mg/ml) and classified them into subjects with AHR and those without AHR according to a cutoff level of PC20 (8.0 mg/ml). Then, we genotyped 12 SNPs on EGFR gene, and estimate total imbalance of haplotypes frequencies within haplotype block between two groups. RESULTS: Seventy-two (38.1%) in 189 subjects exhibited 20% decrease in FEV1 from the baseline values by inhalation of methacholine 8.0mg/ml or less. Significant results were observed in the following haplotype block: rs 4947972 - rs 12718945 - rs 2072454 (block-1), rs 4947972 - rs 12718945 - rs 2227983 (block 2), or rs 4947972 - rs 12718945 - rs 2293347 (block-3). In each haplotype block, higher frequency of a haplotype, C-T-C (block-1), C-T-A (block-2) and C-T-A (block-3), was observed in subjects with AHR than in those without AHR (odds ratio and the corresponding P value; 3.289 and 0.00087 (block-1), 3.436 and 0.00055 (block-2), and 4.036 and 0.00181 (block-3), respectively). No significant differences were observed in serological parameters and pulmonary function between two subject groups. CONCLUSIONS: Our results indicate that the EGFR gene polymorphism might be associated with presence of asymptomatic AHR in young allergic adults. PMID- 20357715 TI - Expression of 3-nitrotyrosine, a marker for peroxynitrite, in nasal polyps of nonatopic patients. AB - BACKGROUND: Several works have reported that nitric oxide and free oxygen radicals are up-regulated in nasal polyposis. This study aimed to assess the distribution of peroxynitrite in nasal polyps from nonatopic patients. Occurrence of peroxynitrite also was analyzed in relation with eosinophil infiltration and epithelial alterations. MATERIAL/METHODS: Hematoxylin and eosin staining was used for histologic study. Peroxynitrite was assessed by 3-nitrotyrosine immunohistochemistry. Quantitative evaluation was done by measuring the total number of eosinophils, the number of 3-nitrotyrosine-positive eosinophils, and the extension of the various epithelial alterations. RESULTS: Hematoxylin and eosin staining showed that the nasal polyp epithelium is characterized by progressive disruption or squamous metaplasia. In both cases, infiltrating eosinophils were found in the epithelium and lamina propria. The regions featuring epithelial disruption exhibited 3-nitrotyrosine immunostaining in eosinophils and epithelial cells; hematoxylin-and-eosin - stained eosinophils and 3-nitrotyrosine - positive eosinophils showed conspicuous variations in number. Within the regions featuring squamous metaplasia, 3-nitrotyrosine-positive eosinophils were rarely found, and the epithelium exhibited 3-nitrotyrosine only in the superficial cells. In these regions, hematoxylin-eosin - stained eosinophils showed slight variations in number. CONCLUSIONS: Peroxynitrite plays a pivotal role in the pathophysiology of nasal polyps. In fact, strong expression of peroxynitrite is associated with epithelial disruption, while poor expression of peroxynitrite is associated with squamous metaplasia. Peroxynitrite could influence afflux of eosinophils in the nasal mucosa; moreover, the total number of eosinophils is not critical in generating alterations of nasal polyp mucosa. PMID- 20357716 TI - Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children. AB - BACKGROUND: In obesity, increased tumor necrosis factor (TNF)-alpha level is involved in the development of insulin resistance. Toll-like receptor (TLR)-4 and TLR2 are expressed in adipose tissue, and polymorphisms of these receptors may influence TNF-alpha secretion from adipocytes. In our study, TNF-alpha, soluble TNF receptor 1 (sTNFR1), and soluble TNF receptor 2 (sTNFR2) levels were determined, and any association between polymorphisms of TLR4 (D299G, T399I), TLR2 (R753Q, R677W), and cytokine levels was assessed in obese children and non obese control subjects. MATERIAL/METHODS: In a cross-sectional study, 79 obese children and 42 matched non-obese control children were investigated. Cytokine levels were measured by enzyme amplified sensitivity immunoassay. TLR4 and TLR2 polymorphisms were determined using polymerase chain reaction - restriction fragment length polymorphism technique. RESULTS: TNF-alpha and sTNFR2 levels in obese children were significantly (P<.01) higher than controls. Significant (P<.05), positive, linear correlations were observed between TNF-alpha, sTNFR2 levels, and BMI. Patients carrying the mutant alleles of TLR4 (299G and 399I) had lower TNF-alpha and sTNFR2 levels compared to patients carrying wild-type alleles (299D and 399T) (TNF-alpha 4.4+/-0.7 pg/mL vs 5.5+/-0.9 pg/mL; sTNFR2 2.9+/-1.2 ng/mL vs 4.4+/-1.1 ng/mL; P<.001). The R753Q polymorphism of TLR2 was not associated with altered cytokine levels, and the R677W polymorphism was not detected in the sample population. CONCLUSIONS: Serum levels of TNF-alpha and its soluble receptors are elevated and associated with increasing BMI values in obese children. Serum cytokine levels, as modifying factors of insulin resistance, may be affected by TLR4 polymorphisms in obese children. PMID- 20357717 TI - Perioperative analgesia of infants during the therapy for retinopathy of prematurity. AB - BACKGROUND: In this retrospective investigation, we compared the main anesthesiologic aspects in the preoperative, perioperative, and postoperative care of 2 different surgical methods (cryotherapy, laser coagulation) for retinopathy of prematurity. MATERIAL/METHODS: A retrospective analysis of analgesia for retinopathy of prematurity was performed for a 14-year period. Infants treated from January 1994 to December 2007 were involved in the study. Before 1997, we performed transconjunctival cryotherapy with ketamine analgesia for 28 newborn infants, while in the last 10 years, laser photocoagulation was done with nalbuphine-diazepam analgesia in 85 cases. RESULTS: Significant differences were verified in gestational age of birth in the group of retinopathy of prematurity patients treated with cryotherapy compared with those treated with laser coagulation 27.9+/-2.7 weeks vs 26.4+/-2.4 weeks (P<.05). The difference in the need for postoperative ventilation (43% vs 19%; P<.05) as well as the number of cases with hypoxemia (54% vs 21%; P<.05) was significant, compared with the group of infants treated with cryotherapy with those treated with laser coagulation. CONCLUSIONS: This study demonstrates that intravenous analgesia (with ketamine or nalbuphine-diazepam) can be used in the surgical treatment of retinopathy of prematurity. PMID- 20357718 TI - Manganese superoxide dismutase (MnSOD) gene (Ala-9Val, Ile58Thr) polymorphism in patients with age-related macular degeneration (AMD). AB - BACKGROUND: Oxidative stress is involved in the pathogenesis of many chronic disorders including cancer, inflammation, and neurologic diseases. Reactive oxygen species (ROS) may play a major role in age-related macular degeneration (AMD). This study investigated the mRNA and protein profiles of manganese superoxide dismutase MnSOD in patients with AMD and healthy controls, while examining its genetic sequence polymorphism (Ala-9Val, Ile58Thr). Our intent was to find a correlation between the expression of MnSOD genes and nucleotide sequence polymorphisms encoded in the gene of the dry and wet form of AMD. MATERIAL/METHODS: We examined 300 unrelated AMD patients and 300 unrelated healthy controls who gave free consent to participate in the study. The MnSOD gene polymorphisms were determined by PCR/RFLP method. We also used real-time RT PCR and ELISA methods to estimate expression of MnSOD mRNA and protein. RESULTS: There were statistically significant differences in the genotype distribution between patients with AMD and controls. Our results showed positive correlations between gene sequence polymorphism and the level of MnSOD mRNA and protein expression. The Ala-9Ala genotype and alanine allele (Ala-9Val sequence polymorphism) is much more frequent in AMD patients than in healthy subjects. Healthy controls who are homozygotes Val/Val and heterozygotes Ala/Val showed lower expression of the MnSOD gene as compared to homozygote Ala/Ala. The lowest expression of MnSOD (homozygotes Val/Val and heterozygotes Ala/Val for wet and dry form of AMD) was noted in patients with AMD. CONCLUSIONS: These data suggest a genetic role of MnSOD polymorphism in the development of age-related degeneration. PMID- 20357719 TI - Menstrual pattern following tubal sterilization. AB - BACKGROUND: We sought to investigate the effects of tubal sterilization over menstrual parameters and determine the timing of the detected influences. MATERIAL/METHODS: We questioned 97 voluntary patients among 301 women who had been subjected to tubal sterilization in our clinic between 1996-2006. Patients were asked via questionnaire about menstrual parameters concerning the 5 years before and after the surgery, which focused on each year separately. Statistical analyses were carried out by considering the preoperative data of patients as controls and postoperative data as the study group. RESULTS: Some kind of pattern change was detected in 7.6% of all patients. Hemorrhage with chunky clots of blood incidence decreased significantly by the second postoperative year (31.9%, 21.6%; P<.05). We had a significant decrease in dysmenorrhea postoperatively in the third, fourth, and fifth years (38.1%, 21.6%, 16.4%, 13.4%; P<.05). While the premenstrual syndrome was 45.3% before surgery, it was 30.9% and 24.7% postoperatively in the fourth and fifth years (P<.05). CONCLUSIONS: Hemorrhage and dysmenorrhea were most frequently seen after tubal sterilization. The statistically significant drop in the mean weekly coital frequency during postoperative period indicates a need for further studies, which might evaluate the reasons behind this reduction. PMID- 20357720 TI - Increased mean platelet volume in chronic hepatitis B patients with inactive disease. AB - BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide, responsible for considerable morbidity and mortality from chronic liver disease. Conflicting findings on the possible association between HBV surface antigen (HBsAg) positivity, indicating inactive HBsAg carrier status, and atherosclerosis have been reported. Platelet activation and aggregation are central processes in the pathophysiology of atherosclerosis. Mean platelet volume, a determinant of platelet activation, is a newly emerging risk factor for atherothrombosis. Elevated MPV levels have been identified as an independent risk factor for myocardial infarction in patients with coronary heart disease, and for death or recurrent vascular events after myocardial infarction. Moreover, increased platelet size has been reported in patients with vascular risk factors such as diabetes mellitus, in patients with acute ischemic stroke, and essential hypertension. According to our knowledge, there has been no previous study of MPV in inactive HBsAg carriers. Therefore, we have investigated the possible association between HBsAg positivity and MPV. MATERIAL/METHODS: We selected 260 inactive HBsAg carriers, and 80 healthy control subjects matched for age, sex, and body mass index. RESULTS: The MPV level was significantly higher in the inactive HBsAg carrier group than in the control group (8.8+/-1.2 fl vs 8.1+/-0.9 fl, P=.001). CONCLUSIONS: Our results suggest that inactive HBsAg carriers tend to have relatively increased platelet activation and an atherothrombotic risk. PMID- 20357721 TI - A case with cardiac tamponade as the first sign of primary gastric signet-ring cell carcinoma treated with combination therapy. AB - BACKGROUND: This report presents a rare patient with cardiac tamponade as the first manifestation of primary gastric signet-ring cell carcinoma. CASE REPORT: A 56-year-old woman with emergent dyspnea, anterior chest oppression, and hypotension was diagnosed as having cardiac tamponade due to massive pericardial effusion. The endoscopic examination of the stomach disclosed gastric cancer in the posterior wall of the antrum and the biopsy showed signet-ring cell carcinoma. The gastric cancer was complicated by malignant pericardial effusion and pleural effusion as well as metastasis to the peripheral lymph nodes and bones. The patient was treated with percutaneous pericardiocentesis followed by systemic chemotherapy (oxaliplatin and sequential 5-fluorouracil plus leucovorin). The pericardial effusion gradually disappeared and there was no cardiac tamponade occurrence. The patient has survived more than 6 months so far. CONCLUSIONS: Cardiac tamponade may originate from a primary gastric signet-ring cell carcinoma. Pericardiocentesis followed by systemic chemotherapy may be effective in controlling such advanced gastric signet-ring cell carcinoma. PMID- 20357722 TI - Compression peroneal neuropathy following a bicycle injury in a child. AB - BACKGROUND: The spectrum of bicycle riding injuries is extremely wide. However, compression peroneal neuropathy complicating a bicycle injury has not been previously reported. CASE REPORT: An 11-year-old girl with common peroneal neuropathy is presented. Her knee was caught in between the chain stay and the crank arm on the left side of her bicycle and was jammed. Clinical examination indicated a motor paralysis producing foot drop and a sensory deficit over the lateral calf and the dorsum of the foot. Magnetic resonance imaging (MRI), although not diagnostic, provided useful information regarding soft tissue injury in relation to the common peroneal nerve's course in the popliteal fossa. An electrodiagnostic (EDX) study was indicative of a common peroneal neuropathy. Complete recovery of the peroneal nerve was noted 7 months post-injury. CONCLUSIONS: Compression peroneal neuropathy may be included in traumatic bicycle related injuries, while the space between the chain stay and the crank arm on the left side of the bicycle may be recognized as potentially hazardous to entrap the rider's leg. PMID- 20357723 TI - Bilateral Baxter's neuropathy secondary to plantar fasciitis. AB - BACKGROUND: Baxter's neuropathy is a nerve entrapment syndrome that results from the compression of the inferior calcaneal nerve. The causes of Baxter's neuropathy include altered foot biomechanics such as flatfoot, plantar calcaneal enthesophytes, and plantar fasciitis. Baxter's neuropathy and causative pathologies such as plantar fasciitis can be identified with the help of typical MRI findings. CASE REPORT: In this report, bilateral Baxter's neuropathy developed in a 42-year-old woman secondarily to bilateral plantar fasciitis. On MR images, fatty atrophy of the abductor digiti minimi muscles was found in both feet, revealing high-signal areas in the T1-weighted images and low-signal areas in the T2-weighted images. Additionally, findings of plantar fasciitis were observed in both feet. CONCLUSIONS: To the authors' knowledge, no case of bilateral Baxter's neuropathy secondarily to plantar fasciitis has been reported. Baxter's neuropathy and causative disorders are easily recognized with help of typical MRI findings. Selective fatty atrophy of the abductor digiti minimi muscle is the unique sign of this neuropathy. Recognition of unique MRI findings of this rare condition that can cause heel pain are important since they provide an effective treatment plan. PMID- 20357724 TI - Implications of positive and negative neuroplasticity on cognition in HIV. AB - HIV cognitive impairments are a common occurrence. Although some of the etiologies of such cognitive impairments are understood, some of the causes are not always straightforward because adults with HIV represent a very heterogenous population. Unfortunately, many of the studies that investigate cognition in this population rely on convenience samples of HIV-positive adults who may lack cognitive stimulation due to poor education or unemployment, both of which can promote negative neuroplasticity. By the same token, other adults with HIV may be cognitively stimulated by their work, educational pursuits, and intellectual interests which may promote positive neuroplasticity which may be protective against cognitive impairments. Implications for how this impacts research as well as prevention and intervention of cognitive impairments are posited. PMID- 20357726 TI - Inactive Hepatitis B carriage, HBV DNA level and biopsy. PMID- 20357727 TI - 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice. AB - BACKGROUND: This study aimed to assess the impact of 99mTc-EDDA/HYNIC-TOC (99mTc TOC) somatostatin receptor scintigraphy (SRS) in clinical practice. MATERIAL/METHODS: One hundred seventeen patients were divided into 6 groups: 1, initial detection and localization of suspected neuroendocrine tumor (NET); 2, tumor staging before therapy; 3, staging of NET of unknown origin, 4, restaging after surgery of primary tumor; 5, diagnosis of solitary pulmonary nodules (SPNs), and 6, follow-up after "cold" somatostatin analogues treatment. RESULTS: In group 1, clinical suspicions were not confirmed in any of the patients; in group 2, most of the primary lesions showed overexpression of somatostatin receptors (SSRT); in group 3, the primary tumor was not identified in any of the patients; in group 4, recurrences were depicted in 7 out of 47 patients; in group 5, only 1 malignant SPN was detected, and in group 6, regression of primary mass and metastases were seen on follow-up SRS in 1 patient. CONCLUSIONS: 99mTc-TOC SRS is useful in staging of SSRT-overexpressing tumors of known and unknown primary origin, as well as in restaging after primary tumor surgery. This method is less effective in detecting suspected NET and assessing SPNs. Further investigation is necessary to evaluate the usefulness of SRS in monitoring patients after biological treatment. PMID- 20357728 TI - Laparoscopic surgery for the management of ovarian endometriomas. AB - BACKGROUND: Treatment for mild and moderate endometriosis is controversial, whereas ovarian endometriomas of diameter > 3 cm must be treated surgically. A minimally invasive and inexpensive surgical approach should be always preferred. The objective of this randomized, prospective, clinical trial was to assess operative time, hemostasis, accuracy, recurrence rates, and pregnancy outcomes of 2 different laparoscopic techniques for management of ovarian endometriomas. MATERIAL/METHODS: Ninety-two patients with ovarian endometriomas were randomized to undergo direct stripping of cystic wall from the initial adhesion site (group A), or circular excision of ovarian tissue around the initial adhesion site and then stripping (group B). Pregnancy outcome results were retrieved at 36 months after surgery. Recurrence rate corresponded to evaluation at 4 and 12 months after surgery performed by transvaginal ultrasound and Ca125 serum level. RESULTS: Direct stripping leads to bleeding more frequently than does circular excision. Hemostasis at the ovarian hilus does show differences between groups; an easy exposure of damage after circular excision reduces execution time. Cumulative pregnancy outcomes at 36 months, and recurrence rates during follow up, did not significantly differ among techniques. CONCLUSIONS: Circular excision of endometrioma cystic wall reduces surgical time, and results in better hemostasis. In addition, excision techniques allow complete removal of the cystic wall in 93% of cases (compared to 74.5% for direct stripping technique), showing differences in recurrence rate, and bringing about a better pregnancy. Data are not statistically significant owing to the small number of collected cases. PMID- 20357729 TI - Women gynecologists' attitude toward their own health. AB - BACKGROUND: Following the publication of the results of Women's Health Initiative in 2002 there have been gross changes in the attitude of women and physicians towards the risks and benefits of hormone replacement therapy (HRT). We evaluated the attitude of women gynecologist towards their own health, including adherence to recommended screening tests and self usage and prescription of hormone replacement therapy. MATERIAL/METHODS: Questionnaires regarding performance of screening tests, self usage and recommendation of HRT were posted by mail to all Israel's women gynecologists. RESULTS: Ninety questionnaires were eligible for analysis (43.2% response rate). Average age was 48+/-7.7 years. Only 7/90 (7.8%) gynecologists smoke regularly and average body mass index was 25+/-3.8 kg/m2. Most participants performed at least one screening tests in the past 2 years. The median interval from the last self breast exam, mammography, gynecologisy exam, Papanicolaou test, colonoscopy and bone density test was 0.2, 1.82, 1.79, 1.95, 3.27 and 1.41 years, respectively. Most of them (68.3%) did not routinely recommend HRT to their patients. The duration of self HRT usage ranged between 1 20 years (average 5.1+/-3.4 years). Most gynecologists (87.7%) recommended continuous estrogen and progesterone for women with their uterus in place. CONCLUSIONS: The health profile of Israeli women gynecologists is chracterized by a high performance of screening tests for cancer and low rate of smoking. Our study also demonstrates that the impact of the results of the WHI trial is still well manifested and most Israeli women gynecologists do not routinely recommend HRT to postmenopausal women. PMID- 20357730 TI - The frequency of depression and menopause-related symptoms in postmenopausal women living in a province in Eastern Turkey, and the factors that affect depressive status. AB - BACKGROUND: This study was designed to determine depression in women in the postmenopausal stage in Elazig city, located in Eastern Turkey, and determine the factors affecting depressive status. MATERIAL/METHODS: The sample included 546 women and of these, 519 could be contacted. A questionnaire was conducted with the women who were included in the study. This included demographic properties, which are thought to affect depression. Subjects were given the Beck Depression Inventory (BDI). RESULTS: In total, 97.7% of women reported that they experienced a problem or had complaints during menopause, while 54.9% reported that they experienced problems in their sexual lives. The mean BDI score of women was 17.01+/-8.75. The ratio of women whose total scores were higher than the breakpoint of 17 was 42.2%. Single, widowed, and divorced women had higher ratios than married women; primary school or lower education women had higher ratios than high school or lower education graduate women; the women who reported that they had problems in their sexual lives had higher ratios than the other women within the survey; the women who were subject to violence at any time during their lives had higher ratios than the women who had not experienced violence (P<.05). CONCLUSIONS: The frequency of depression symptoms in women living in Elazig is high. The information and services that the local women receive about menopause are inadequate. PMID- 20357731 TI - Aminofeel improves the sensitivity to taste in patients with HCV-infected liver disease. AB - BACKGROUND: Patients with chronic liver diseases have a taste disorder and altered zinc metabolism. We investigated the effects of a supplement enriched with branched-chain amino acids (BCAA) (Aminofeel) on sensitivity to different tastes in patients with hepatitis C virus (HCV) infected liver disease. MATERIAL/METHODS: Nine patients (mean age 63.3+/-9.1 years) with HCV-related liver diseases were identified and examined for sensitivity to different tastes. Eight patients had no awareness of taste disorders, and 3 patients had oral lichen planus. We examined 4 tastes (sweet, salty, sour, and bitter) using a Taste Disk and sensitivity to different tastes was rated on a 6-point scale (I, II, III, IV, V, and VI). Each patient was given one sachet of Aminofeel after breakfast and another at bedtime for 90 days. RESULTS: Only one patient was aware of a taste disorder before administration of Aminofeel, but 4 patients had decreased gustatory sensitivity in the sour taste test, and 2 had it in the bitter taste test. Sensitivity to sour tastes significantly increased after the administration of Aminofeel(R) (P=0.03). Sensitivity to sweet tastes increased after the administration of Aminofeel (P=0.06). Zinc value significantly increased after the administration of Aminofeel (P=0.02). CONCLUSIONS: Patients with HCV-infected liver disease have decreased sensitivity to different tastes and decreased zinc levels. Some patients were unaware that they had a taste disorder. Aminofeel improved sensitivity to different tastes and increased zinc values. Thus, Aminofeel is a useful therapeutic agent for taste disorders. PMID- 20357732 TI - Evidence-based treatment limitations prevent any therapeutic recommendation for acute poststreptococcal glomerulonephritis in children. AB - The majority of children with the epidemic form of acute post-streptococcal glomerulonephritis (APSGN) have an excellent prognosis, which contrasts with the poor long-term outcome of sporadic cases. Therapy is largely supportive. Rarely, the disease shows long-term complications, worsening to chronic kidney disease requiring long-term interventional measures. To compare the effectiveness of different therapeutic strategies for the prevention and treatment of APSGN in childhood, the authors reviewed randomized controlled trials on the prevention and treatment of APSGN in children. Nine studies fit the inclusion criteria. Primary outcomes were the development of APSGN, the effectiveness of medication for controlling hypertension, and the development of chronic renal failure in patients with crescentic glomerulonephritis. No advantages of antimicrobials (cefuroxim, ceftibuten, and others) given for 5 days were found over penicillin V given for 10 days (4 trials). Nifedipine showed advantages in controlled acute hypertension (1 trial). ACE inhibitors (captopril and enalapril) had better control of blood pressure and echocardiographic changes than other antihypertensive drugs/diuretics (2 trials). The use of combined immunosuppressants for crescentic poststreptococcal glomerulonephritis showed no advantages over supportive therapy alone (1 study). The studies were of small number and with limitations that seriously weaken the results. PMID- 20357733 TI - Advances in the research of fetal DNA in maternal plasma for noninvasive prenatal diagnostics. AB - Molecular analysis of fetal DNA present in the maternal circulation allows noninvasive, early, and precise determination of fetal genetic status in prenatal diagnostics. The most common clinical applications, i.e. prenatal gender determination and fetal RhD genotyping, are possible already in the first trimester using specialized protocols for DNA isolation from plasma and subsequent real-time PCR detection. Recent advances in molecular techniques enable other applications of fetal DNA purified from maternal plasma samples. Chromosomal abnormalities (e.g. trisomy 21) can be diagnosed by digital PCR, which offers higher accuracy in quantifying DNA sequences than standard real-time PCR. Digital PCR, but also MALDI-TOF, are suitable for detecting point mutations, widening the spectrum of applications to monogenic diseases. The ongoing lowering of costs for massively parallel sequencing might lead to replacement of most of the other currently used approaches. Adopting specialized protocols for the purification of fragmented circulating fetal DNA and improving the bioinformatic analysis of raw data can bring us closer to sequencing the fetal genome as the ultimate goal of prenatal DNA diagnostics, with wide-ranging medical applications. The discussion and solution of ethical issues beyond early fetal gender or paternity determination is hanging just behind the rapid technical progress of noninvasive prenatal DNA diagnostics. PMID- 20357734 TI - Short-term effects of the activator in skeletal class II division 1 patients with different vertical skeletal pattern. A retrospective study. AB - AIM: The aim of this retrospective study was to analyse the effectiveness of Andresen appliance in inducing an increased mandibular dimension and, above all, to test the "null" hypotesis that the patients' vertical skelettofacial morfology could influence this increase using the Ricketts' method of VERT. METHODS: Cephalometric records of 42 skeletal class II patients treated at the Orthodontic Department of Catania University were randomly selected. The sample was divided for vertical facial patterns, according to the facial classification method of Ricketts (VERT), into three groups: brachyfacial, mesiofacial and dolicofacial. Ten landmarks were located on the lateral cephalometric radiographs; growth in the horizontal-sagittal direction and in the vertical direction was evaluated using the measurements of total mandibular length (Co-Gn, Co-Pg, Ar-Pg, Ar-Gn), mandibular sagittal position (SNB, ANB) and mandibular ramus height (S-Go, Ar-Go, Co-Go). The intragroup comparisons were made using two tailed t-tests, while the intergroup comparisons were analyzed statistically using the Kruskal-Wallis test. RESULTS: The cephalometric values before (T0) and after (T1) treatment showed significant changes for the majority of the cephalometric variables in each group. Our findings demonstrated a statistically significant greater increase of mandibular dimension in the brachyfacial group, while similar results were found for mesiofacial and dolichofacial groups. CONCLUSION: The "null" hypothesis, that the skeletal pattern of subjects could influence the increase of mandibular dimension after Andresen treatment, had to be accepted: the brachyfacial patients showed a greater anterior mandibular displacement when compared to mesiofacial or dolichofacial group. PMID- 20357735 TI - Retrospective analysis of 521 endosseous implants placed under antibiotic prophylaxis and review of literature. AB - AIM: Antibiotic prophylaxis in surgical implants has not a consensus in the scientific world. This is due both to reports and statistical studies with contradictory results, both to the risk of severe anaphylactic reactions and the emergence of antibiotic resistance and, finally, to the lack of published RCTs. The purpose of this study is to retrospectively analyze and assess the success of surgical therapy with endosseous implants inserted under antibiotic prophylaxis at the Department of Oral Sciences "S. Palazzi", University of Pavia. The data presented are compared to those published in international literature. The work is complemented by a statistical data analysis in order to propose a statistically valid judgement on the effectiveness of antibiotic prophylaxis in preventing postoperative infections. METHODS: Retrospective observational study with an average follow-up of 4.5 months, until the abutment connection. Furthermore, after extensive review of the literature, published data are compared with what retrieved in our department. Patients operated consecutively from June 2002 to December 2007. Review of literature data concerning the influence of antibiotic prophylaxis on the implant success. RESULTS: The data relating to post-operative complications encountered at the Division of Oral Surgery, University of Pavia and the comparison with those presented in the bibliography indicate statistically significant differences in favor of the antibiotic prophylaxis used in our department. CONCLUSION: There were no anaphylactic reactions recorded. It seems advisable to perform implantology with prophylactic antibiotic coverage. PMID- 20357736 TI - Clinical and computerized evaluation in study of temporo-mandibular joint intracapsular disease. AB - AIM: In this work authors show a diagnostic criteria in study of TMID: neuro occlusal clinical evaluation (NOE), T-Scan 2 system and surface electromyography (sEMG). METHODS: Nine patients 25-30 years old with TMID problem and 9 healthy group control have been selected and examined. On each patients it has been performed NOE, T-Scan and sEMG test. NOE has been calculated on each patient photos lateral mandibular excursion angle called: masticatory functional angle (AFM). T-Scan System is a computerized occlusal analyzer that provide in-depth understanding of the overall balance of the occlusion. At the same time of T-Scan record sEMG tests, in resting position and in maximum clench, have been performed. RESULTS: In healthy control there were no AFM difference. In no healthy group there were difference between the two AFM greater than 6 degrees. T Scan COF showed how in healthy group control there was never a difference of COF greater than 5%. In no healthy group the difference were greater than 5% P<0.05. T-scan showed difference of time force in maximum intercuspidation (MIFT) in healthy respect TMID patients. In healthy patients MIFT was higher than TMID patients P<0.05. sEMG test showed in non healthy group a great asymmetrical activation of masseter (MM). MM activation were greater on side affected by joint sound than the balance side P<0.001. sEMG show how in TMID patients maximum masseter activation is always lower than maximum masseter activation of healthy subjects P<0.001. CONCLUSION: Neuro occlusal clinical evaluation (NOE) in TMID patients is supported by instrumental evaluation. PMID- 20357737 TI - Effect of hydroxyapatite-based biomaterials on human osteoblast phenotype. AB - The present study evaluated human primary osteoblasts and two different osteoblast-like cell lines behaviour when cultured in presence of different hydroxyapatite-based (HA) biomaterials (SINTlife-FIN-CERAMICA S.p.a., Faenza, Italy; Bio-Oss, Geistlich Biomaterials, Woulhusen, Switzerland; Biostite-GABA Vebas, San Giuliano Milanese, MI, Italy), focusing attention on the effect of HA/Biostite in terms of modulation of osteoblastic differentiation. Analysis were about adhesion, proliferation and mineralization activity. Runt-related transcription factor 2 (Runx2), Estrogen Receptor alpha (ERalfa) expression and alkaline phosphatase activity (ALP) were measured as osteoblastic differentiation markers. Determination of viable cells was done with MTT colorimetric assay. Scanning electron microscopy (SEM) analysis was performed on biomaterial-treated cells. All hydroxyapatite-based biomaterials didn't affect cells morphology and viability, whereas only presence of HA/Biostite improved cells adhesion, growth and differentiation. Adhesion and spreading of the primary cells on HA/Biostite were the same showed by two different osteoblast-like cell lines. These results have important implications for both tissue-engineered bone grafts and enhancement of HA implants performance, to develop new teeth's supporting structure therapies and replacement. PMID- 20357738 TI - Cleidocranial dysplasia: etiology and stomatognathic and craniofacial abnormalities. AB - Cleidocranial dysplasia (CCD) is a rare disorder which is inherited as an autosomal genetic trait. It is characterized by defective ossification, delayed bone and tooth development, stomatognathic and craniofacial abnormalities, and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. The purpose of this review is to collect and analyze data in the literature on orofacial typical manifestations of the syndrome and to present knowledge of the eziopatogenics mechanisms of the CCD. Clinical, genetic, aetiopathogenetic studies on this syndrome were compliled through a systematic approach using Medline. This review reports the cranio-facial features and dental characteristics of the CCD on the basis of all data in the literature. This review pays particular attention on the eziopatogenics mechanisms of CCD and summarises the results of the most recent studies. Access to detailed review of the etiopathogenic mechanisms of CCD is a fundamental support for clinicians as it can allow to make an informed assessment regarding the most effective choice of therapy. The review shows how an interdisciplinary approach is necessary for an appropriate treatment since CCD patients suffer from a skeletal third class, transverse deficiency of the maxilla, supernumerary permanent teeth and deficient eruption of impacted permanent teeth. PMID- 20357739 TI - Oral and craniofacial findings in a patient with methylmalonic aciduria and homocystinuria: review and a case report. AB - Combined methylmalonic aciduria and homocystinuria (MMA-HC) is a rare metabolic disease characterized by an inborn defect in B12 vitamin metabolism. This case report concerns an 11-year-old patient with MMA-HC, which developed during the neonatal period. The patient shows some of the facial features that were already reported in the literature (high forehead, large floppy, low-set ears, flat philtrum and hypotonia of perioral and masticatory muscles) but no dolichocephalic skull nor long face. The patient also shows signs that had not been previously described: epicanthal folds, broad nasal bridge, long and flat philtrum, amimic expression and, particularly, a postural alteration (the head is rotated and bent towards the left shoulder, which is lower than the right one). Such alteration can be attributed to visual impairment and is responsible for breaking muscular and skeletal balance in the frontal plane, thus causing the horizontal planes of both maxillary bones to converge towards the right--as highlighted by the cephalometric analysis of the Teleradio-graph of the skull in Posteroanterior projection according to Ricketts. As for the patient's teeth, eruption times are normal, but there are anomalies of shape (chisel-like central incisors). As far as dental caries is concerned, the patient's DMFT is 4 (D=4, M=0, F=0). This clinical case highlights the need for dental prevention programs suggested by the pediatrician once the pathology is diagnosed. PMID- 20357740 TI - Angina bullosa hemorrhagica: report of 4 cases. AB - Angina bullosa hemorrhagica is characterized by the sudden appearance of solitary or multiple hemorrhagic blisters on oral mucosa, with diameters ranging from 2 mm to 3 cm. The soft palate is most commonly affected, but angina bullosa hemorrhagica may also appear on the buccal mucosa, lips and tongue border. Clinically, the blisters have a dark red to purple appearance, and may or may not be painful. The blisters usually break, releasing bloody content and leaving an ulcer surface that heals within 7 to 10 days. In this article the authors describe four cases of angina bullosa hemorrhagica attended in Stomatology Department of Dental School, Sao Paulo State University. In case 1, a 29-year-old male presented with a sudden hemorrhagic blister on the soft palate. A drainage was performed and after seven days of follow-up the patient reported no symptoms. In case 2, a 63-year-old male presented complaining of a blister on the palate six days earlier that had spontaneously broken. General exam showed hypertension under medical control. An incisional biopsy was performed and after seven days follow-up the healing was completed. In case 3, a 61-year-old male arrived complaining of a sudden appearance of an hemorrhagic blister on the soft palate that had spontaneously broken. The patient had systemic hypertension under medical control. The ulcer healed in 10 days follow-up. In case 4, a 49-year-old woman presented complaining of pain and an ulcer on the soft palate. The patient reported the rapid onset of a blood blister during a meal that broke in few minutes. The resolution occurred after 14 days. Angina bullosa hemorrhagica seems to be more common than reported in the literature and knowledge of the condition is important to right diagnosis and approach when necessary. PMID- 20357741 TI - Idiopathic gingival fibromatosis: description of two cases. AB - Gingival fibromatosis is an enlargement localized or generalized of the gingival tissue characterized by an expansion and accumulation of the connective tissue, predominantly type I collagen, with occasional presence of increased number of cells, supposed fibroblastic proliferation. Gingival fibromatosis can be induced as a side effect of systemic drugs, such as phenytoin, cyclosporin, and nifedipine, or due to hereditary factors. However, in some cases, the gingival overgrowth is idiopathic. This paper reports two cases of idiopathic gingival fibromatosis and discusses the diagnosis, histopathological features, treatment and immunohistochemical evaluation of myofibroblasts of this condition. The tissues removed were fixed in formalin, and sections used for hematoxylin and eosin and Masson tricromic stain. To determine the presence of myofibroblasts, we performed immunohistochemistry against a-SMA protein. Histological examination revealed epithelial hyperplasia with long rete pegs and increase in the dense fibrous connective tissue. The Masson tricromic stain revealed wide bundles of collagen strongly stained. It was showed negative labeling to a-SMA. These results strongly suggest that myofibroblasts are not involved in gingival overgrowth in the cases of IGF reported. Future studies will be necessary to determine the pathogenesis of idiopathic gingival fibromatosis. PMID- 20357742 TI - Medication therapy for peripheral arterial disease. Foreword. PMID- 20357743 TI - Three-year cardiovascular events and disease progress in patients with peripheral arterial disease: results from the Japan Medication Therapy for Peripheral Arterial Disease (J-METHOD). AB - AIM: To investigate the current status of peripheral arterial disease (PAD) drug treatment in Japan, and the effects of drug treatment, risk factors, and complications on disease progress and onset of cardiovascular events in PAD patients. METHODS: In this prospective observational cohort study, 557 PAD patients were followed up for 3 years, and the current status of PAD treatment, risk factors, and cardiovascular events were monitored. RESULTS: Three drugs, i.e., beraprost sodium, cilostazol, and aspirin, were most frequently used. The patients who had undergone vascular reconstruction of the lower limbs before enrollment showed significant improvement in ABI. Among the patients who had not undergone vascular reconstruction before enrollment, there was a significant improvement in ABI after treatment with beraprost. During the observation period, cardiovascular deaths occurred in 35 patients (6.3%), heart diseases in 63 (11.3%), brain diseases in 39 (7.0%), and events in the lower limbs in 94 (16.9%). The factors affecting the increase of the cardiovascular events were explored by multivariate analysis (Cox regression analysis). As a result, age (75 years or older), ischemic heart disease and increase in severity on the Fontaine classification were identified as significant factors for cardiovascular deaths, whereas kidney disorders and increase in severity on the Fontaine classification were identified for heart diseases, the number of oral drugs for treating PAD was identified for brain diseases, and age (younger than 75 years), dialysis, ABI (less than 0.7) and aspirin were identified for the events in the lower limbs. CONCLUSION: As a result of the three-year follow-up on the Japanese PAD cohort, the current status of PAD treatment, risk factors, and cardiovascular events could be identified. PMID- 20357744 TI - Orally active prostacyclin analogue for cardiovascular disease. AB - Prostacyclin has vasoprotective effects such as vasodilation and antiplatelet aggregatory activity. A relative deficiency of prostacyclin contributes to the pathogenesis of cardiovascular disease including pulmonary artery disease (PAH). Inconvenient intravenous dosing of prostacyclin led to the development of more stable, an orally active analogue: beraprost. It is a chemically stable prostacyclin analogue owing to its cyclo-pentabenzofuranyl structure and produces strong vasodilation and inhibition of platelet aggregation. To date, beraprost has been used in the treatment of PAH and peripheral arterial disease (PAD). Recently, we have shown that beraprost induces neovascularization in ischemic myocardium by enhancement of bone marrow cell mobilization. Interestingly, meta analysis of clinical studies for PAD has shown that repeated administration of beraprost decreases the number of cardiovascular events. These results suggest that oral administration of beraprost has beneficial effects on cardiovascular disease. Orally active prostacyclin analogues, are promising drugs for the treatment of cardiovascular disease. PMID- 20357745 TI - Roles of prostanoids in the pathogenesis of cardiovascular diseases. AB - The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified. PMID- 20357746 TI - Novel effects of beraprost sodium on vasculatures. AB - Beraprost sodium (BPS) is a stable orally active prostacyclin analogue with vasodilatory and anti-platelet effects, and has been widely used as therapeutics for pulmonary artery hypertension and chronic arterial obstruction. In order to elucidate its effects on endothelium, we first examined the short-term effects of BPS on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation using bovine aortic endothelial cells. Short-term treatment of BPS induced NO production as well as eNOS phosphorylation at Ser-1179 mediated via cAMP/protein kinase A (PKA) pathway. The effects of BPS on capillary-like tube formation were next determined using human umbilical vein ECs (HUVECs)/normal human dermal fibroblasts co-culture system. BPS was observed to induce capillary-like tube formation mediated via cAMP/PKA pathway, but not via NO generation. Finally, we performed DNA microarray analyses using RNA extracted from BPS treated HUVECs. Interestingly, BPS up-regulated several genes involved in angiogenesis, anti atherosclerosis, and endothelial function, while down-regulated several genes involved in atherosclerosis. Our data therefore indicate that BPS may be useful not only for patients with pulmonary artery hypertension and chronic arterial obstruction, but also for general atherosclerotic patients complicated with endothelial dysfunction. Further studies are needed to clarify molecular mechanisms of these BPS effects including the involvement of peroxisome proliferator-activated receptor-delta. PMID- 20357747 TI - Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. AB - Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. PGI2 synthase (PTGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PTGIS gene is localized to 20q13.11-13 and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction, and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PTGIS gene and that they may influence the risk of cardiovascular disease. Thus, individualized management strategies, such as the administration of PGI2 analogues, could be selected for variants of this gene, to help prevent the development of cardiovascular disease. PMID- 20357748 TI - Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques. AB - AIM: Prostaglandin (PG) receptor agonists are frequently used for the pharmacological treatment of arteriosclerosis obliterans (ASO). In particular, the PG receptors EP2 and IP stimulate vasodilation and inhibit platelet aggregation, biological processes thought to be protective against ASO and important for physiological homeostasis. However it is uncertain whether EP2 and IP exist in diseased arteries, or what their distribution within the artery might be. In this study, we analyzed the distribution of these PG receptors in patients with severe ASO to determine the potential application of stimulation of these receptors as targets for pharmacological treatment. METHODS: We collected segments of atherosclerotic femoral arteries during femoropopliteal bypass surgery and determined the expression levels of EP2 and IP receptors by western blotting. Immunofluorescence was used to observe receptor localization. RESULTS: Findings of western blotting showed an increased Cox-2 expression in patients with ASO. The EP2 as well as IP receptors were each induced approximately 3-fold in comparison to normal samples. The expression of these receptors was increased in the intimal layer as well as the medial layer; their expression was also detectable within the atherosclerotic plaque. CONCLUSION: We observed induction of the PG receptors EP2 and IP in atherosclerotic femoral arteries in the arterial intima, medial layer, as well as the associated atherosclerotic plaque. These results suggest that receptor-selective PG agonists specifically target atherosclerotic arteries and therefore, may find potential application in the pharmacological management of patients with ASO. PMID- 20357749 TI - The efficacy of oral beraprost sodium, a prostaglandin I2 analogue, for treating intermittent claudication in patients with arteriosclerosis obliterans. AB - AIM: This study aimed to evaluate the effect of oral beraprost sodium, a prostaglandin I2 analogue, on symptoms of intermittent claudication in patients with arteriosclerosis obliterans. The research design consisted of a before and after treatment study without comparison groups. The subjects comprised arteriosclerosis obliterans patients who experienced intermittent claudication. Furthermore, this study aimed to assess the mechanism of action of beraprost sodium via blood sampling and measurements of flow-mediated vasodilatation before and after treatment. METHODS: The study was performed prospectively in 7 patients with arteriosclerosis obliterans. Beraprost sodium (40 microg) was orally administered to 7 patients at study entry, followed by administration of 120 microg/day for 12 weeks. Blood sampling and measurements of flow-mediated vasodilatation were performed before and after treatment at study entry, 4 weeks, and 12 weeks after treatment. Treadmill exercise tests were performed three times at study entry, 4 weeks, and 12 weeks after treatment. The ankle-brachial index (ABI) was measured at rest and after exercise. RESULTS: Pain-free walking distances increased by 138% at 12 weeks after treatment. Maximum walking distances increased by 133%. The ABI was significantly increased at 4 weeks and 12 weeks after treatment at rest. Endothelin-1 levels tended to be decreased at 1 h after administration of 40 microg beraprost sodium. N(G),N(G)-dimethyl-L arginine, nitrate ions, and flow-mediated vasodilatation. CONCLUSION: Beraprost sodium tended to decrease endothelin-1 levels and improved symptoms of intermittent claudication in patients with arteriosclerosis obliterans. PMID- 20357750 TI - Conservative treatment for patients with intermittent claudication. AB - AIM: The effect of pharmacotherapy or supervised exercise training on patients with intermittent claudication was assessed. METHODS: One hundred patients with stable intermittent claudication due to arteriosclerosis obliterans were analyzed. We divided the patients into 2 groups: patients treated by pharmacotherapy alone (Group A: 39 claudicants) and patients treated by supervised exercise training and pharmacotherapy (Group B: 61 claudicants). The changes in ankle-brachial pressure index (ABI) and recovery time of ABI after a 40-m walk (RT(40)) and absolute claudication distance (ACD) on a treadmill before and after each treatment were assessed. RESULTS: In Group A, RT(40) decreased from 9.5 +/- 5.8 min at the baseline to 6.4 +/- 3.5 min after 6 months (P=0.0002). In Group B, it decreased from 9.7+/-5.2 min at the baseline to 6.3+/ 4.2 min after 3 weeks (P<0.0001). In Group A, ACD increased from 249+/-177 m at the baseline to 317+/-168 m after 6 months (P=0.0003). In Group B, it increased from 143+/-90 m at the baseline to 257+/-161 m after 3 weeks (P<0.0001). CONCLUSION: Hemodynamics and walking ability were improved by either short-term supervised exercise training or midterm pharmacotherapy. RT(40) may be useful for predicting the effect of conservative treatment on intermittent claudication. Greater increases in ACD after treatment can be achieved in claudicants with a shorter RT(40) before conservative treatment. PMID- 20357751 TI - Current status of the medical expenses for the treatment of arteriosclerosis obliterans in Japan. AB - AIM: We aimed to determine the current status of the medical expenses for the treatment of arteriosclerosis obliterans (ASO) and evaluate the cost effectiveness of the medical practices employed in ASO treatment in Japan. METHODS: We performed a prospective observational study using 140 ASO patients. The cost of the medical practices comprised the costs of outpatient treatment, pharmacological agents, and hospitalization. To compare the average monthly costs, the patients were divided into preintervention, postintervention, or conservative-therapy groups. To compare the total costs and effectiveness of each treatment, the patients who had first visited our division during the study period were classified into surgery, endovascular-revascularization (EVR), or conservative-therapy groups. The adverse reactions of the 4 most popular agents for ASO were investigated, and bleeding events were assessed specifically. RESULTS: The average monthly costs for outpatient treatment and pharmacological agents were yen 168,002 in conservative cases, yen 149,871 in preoperation cases, and yen 128,527 in postoperation cases. The mean total costs were yen 5,407,950 in conservative cases, yen 7,375,290 in surgical cases, and yen 2,631,650 in EVR cases. The average change of the gauge in clinical status was 0.57 in conservative cases, 2.13 in surgical cases, and 2.25 in EVR cases. Warfarin induced more bleeding complications than the other agents. CONCLUSION: The costs of pharmacological agents represented much of the medical costs in any treatment groups. PMID- 20357752 TI - Application of stopped-flow kinetics methods to investigate the mechanism of action of a DNA repair protein. AB - Transient kinetic analysis is indispensable for understanding the workings of biological macromolecules, since this approach yields mechanistic information including active site concentrations and intrinsic rate constants that govern macromolecular function. In case of enzymes, for example, transient or pre-steady state measurements identify and characterize individual events in the reaction pathway, whereas steady state measurements only yield overall catalytic efficiency and specificity. Individual events such as protein-protein or protein ligand interactions and rate-limiting conformational changes often occur in the millisecond timescale, and can be measured directly by stopped-flow and chemical quench flow methods. Given an optical signal such as fluorescence, stopped-flow serves as a powerful and accessible tool for monitoring reaction progress from substrate binding to product release and catalytic turnover(1,2). Here, we report application of stopped-flow kinetics to probe the mechanism of action of Msh2 Msh6, a eukaryotic DNA repair protein that recognizes base-pair mismatches and insertion/deletion loops in DNA and signals mismatch repair (MMR)(3-5). In doing so, Msh2-Msh6 increases the accuracy of DNA replication by three orders of magnitude (error frequency decreases from approximately 10(-6) to 10(-9) bases), and thus helps preserve genomic integrity. Not surprisingly, defective human Msh2 Msh6 function is associated with hereditary non-polyposis colon cancer and other sporadic cancers(6-8). In order to understand the mechanism of action of this critical DNA metabolic protein, we are probing the dynamics of Msh2-Msh6 interaction with mismatched DNA as well as the ATPase activity that fuels its actions in MMR. DNA binding is measured by rapidly mixing Msh2-Msh6 with DNA containing a 2-aminopurine (2-Ap) fluorophore adjacent to a G:T mismatch and monitoring the resulting increase in 2-aminopurine fluorescence in real time. DNA dissociation is measured by mixing pre-formed Msh2-Msh6 G:T(2-Ap) mismatch complex with unlabeled trap DNA and monitoring decrease in fluorescence over time(9). Pre-steady state ATPase kinetics are measured by the change in fluorescence of 7-diethylamino-3-((((2-maleimidyl)ethyl)amino)carbonyl) coumarin) labeled Phosphate Binding Protein (MDCC-PBP) on binding phosphate (Pi) released by Msh2-Msh6 following ATP hydrolysis(9,10). The data reveal rapid binding of Msh2-Msh6 to a G:T mismatch and formation of a long-lived Msh2-Msh6 G:T complex, which in turn results in suppression of ATP hydrolysis and stabilization of the protein in an ATP-bound form. The reaction kinetics provide clear support for the hypothesis that ATP-bound Msh2-Msh6 signals DNA repair on binding a mismatched base pair in the double helix. F PMID- 20357753 TI - The ratio of aminotransferase to platelets is a useful index for predicting hepatic fibrosis in hemodialysis patients with chronic hepatitis C. AB - Percutaneous liver biopsy is the gold standard for staging hepatic fibrosis of hemodialysis patients with chronic hepatitis C before renal transplantation or antiviral therapy. Concerns exist, however, about serious post-biopsy complications. To evaluate a more simple approach using standard laboratory tests to predict hepatic fibrosis and its evolution, we studied 279 consecutive hemodialysis patients with chronic hepatitis C and a baseline biopsy. Among them, 175 receiving antiviral therapy underwent follow-up biopsy to evaluate the histological evolution of fibrosis. Multivariate analysis of routine laboratory tests at baseline showed the aspartate aminotransferase-to-platelet ratio index was an independent predictor of significant hepatic fibrosis. The areas under curves of this ratio to predict fibrosis stages F2-4 were 0.83 and 0.71 in the baseline and follow-up sets; and 0.75 and 0.80 respectively, for patients with sustained or non-sustained virological response groups in the follow-up sets. By a judicious setting of cut-off levels for the baseline and non-sustained groups, and the sustained virological response group, almost half and 60 percent of the baseline and follow-up sets could be correctly diagnosed without biopsy. Our study found the aminotransferase-to-platelet ratio index is accurate and reproducible for assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C. Applying this simple index could decrease the need of percutaneous liver biopsy in this clinical setting. PMID- 20357754 TI - Disconnection of the entorhinal cortex and dorsomedial striatum impairs the sensitivity to instrumental contingency degradation. AB - The capacity to detect changes in the causal efficacy of actions is mediated by a number of brain areas, including the entorhinal cortex (EC) and the posterior part of the dorsomedial striatum (pDMS). In this study we examined whether interactions between the EC and pDMS are required to detect changes in the instrumental contingency. Rats that received EC-pDMS disconnection lesions, that is, unilateral cell body lesions of the EC and contralateral dopamine depletions of the pDMS, were trained to press two levers, with one delivering food pellets and the other a sucrose solution. Thereafter, we tested whether rats were sensitive (1) to a selective devaluation of the value of one of two outcomes using a specific satiety procedure, and (2) to a selective degradation of one of two contingencies controlling instrumental choice behavior. Our results reveal that rats with EC-pDMS disconnection lesions were sensitive to outcome devaluation. However, unlike rats with sham lesions or unilateral EC and pDMS lesions, rats with EC-pDMS disconnection lesions showed a reduced sensitivity to contingency degradation. These findings suggest that EC and pDMS may be part of a neural system that supports the detection of changes in the causal relationship between an action and its consequences. PMID- 20357755 TI - FAAH-/- mice display differential tolerance, dependence, and cannabinoid receptor adaptation after delta 9-tetrahydrocannabinol and anandamide administration. AB - Repeated administration of Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of Cannabis sativa, induces profound tolerance that correlates with desensitization and downregulation of CB(1) cannabinoid receptors in the CNS. However, the consequences of repeated administration of the endocannabinoid N-arachidonoyl ethanolamine (anandamide, AEA) on cannabinoid receptor regulation are unclear because of its rapid metabolism by fatty acid amide hydrolase (FAAH). FAAH(-/-) mice dosed subchronically with equi-active maximally effective doses of AEA or THC displayed greater rightward shifts in THC dose-effect curves for antinociception, catalepsy, and hypothermia than in AEA dose-effect curves. Subchronic THC significantly attenuated agonist-stimulated [(35)S]GTP gamma S binding in brain and spinal cord, and reduced [(3)H]WIN55,212 2 binding in brain. Interestingly, AEA-treated FAAH(-/-) mice showed less CB(1) receptor downregulation and desensitization than THC-treated mice. Experiments examining tolerance and cross-tolerance indicated that the behavioral effects of THC, a low efficacy CB(1) receptor agonist, were more sensitive to receptor loss than those of AEA, a higher efficacy agonist, suggesting that the expression of tolerance was more affected by the intrinsic activity of the ligand at testing than during subchronic treatment. In addition, the CB(1) receptor antagonist, rimonabant, precipitated a markedly reduced magnitude of withdrawal in FAAH(-/-) mice treated subchronically with AEA compared with mice treated repeatedly with THC. The findings that repeated AEA administration produces lesser adaptive changes at the CB(1) receptor and has reduced dependence liability compared with THC suggest that pharmacotherapies targeting endocannabinoid catabolic enzymes are less likely to promote tolerance and dependence than direct acting CB(1) receptor agonists. PMID- 20357756 TI - Stress impairs GABAergic network function in the hippocampus by activating nongenomic glucocorticoid receptors and affecting the integrity of the parvalbumin-expressing neuronal network. AB - Stress facilitates the development of psychiatric disorders in vulnerable individuals. It affects physiological functions of hippocampal excitatory neurons, but little is known about the impact of stress on the GABAergic network. Here, we studied the effects of stress and a synthetic glucocorticoid on hippocampal GABAergic neurotransmission and network function focusing on two perisomatic interneurons, the parvalbumin (PV)- and the cholecystokinin (CCK) positive neurons. In acute hippocampal slices of rat, application of the potent glucocorticoid receptor (GR) agonist dexamethasone (DEX) caused a rapid increase in spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons. This effect was mediated by a nongenomic GR that evoked nitric oxide (NO) release from pyramidal neurons. Retrograde NO signaling caused the augmentation of GABA release from the interneurons and increased CCK release, which in turn further enhanced the activity of the PV-positive cells. Interestingly, chronic restraint stress also resulted in increased sIPSCs in CA1 pyramidal neurons that were Ca(2+)-dependent and an additional DEX application elicited no further effect. Concomitantly, chronic stress reduced the number of PV-immunoreactive cells and impaired rhythmic sIPSCs originating from the PV positive neurons. In contrast, the CCK-positive neurons remained unaffected. We therefore propose that, in addition to the immediate effect, the sustained activation of nongenomic GRs during chronic stress injures the PV neuron network and results in an imbalance in perisomatic inhibition mediated by the PV and CCK interneurons. This stress-induced dysfunctional inhibitory network may in turn impair rhythmic oscillations and thus lead to cognitive deficits that are common in stress-related psychiatric disorders. PMID- 20357757 TI - Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. AB - Bipolar disorder, characterized by extreme manic and depressive moods, is a prevalent debilitating disease of unknown etiology. Because mood stabilizers, antipsychotics, antidepressants, and mood-regulating neuromodulators increase the inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3), we hypothesized that deficient GSK3 serine-phosphorylation may increase vulnerability to mood-related behavioral disturbances. This was tested by measuring behavioral characteristics of GSK3 alpha/beta(21A/21A/9A/9A) knockin mice with serine-to-alanine mutations to block inhibitory serine-phosphorylation of GSK3. GSK3 knockin mice displayed increased susceptibility to amphetamine induced hyperactivity and to stress-induced depressive-like behaviors. Furthermore, serine-phosphorylation of GSK3 was reduced during both mood-related behavioral responses in wild-type mouse brain and in blood cells from patients with bipolar disorder. Therefore, proper control of GSK3 by serine phosphorylation, which is targeted by agents therapeutic for bipolar disorder, is an important mechanism that regulates mood stabilization, and mice with disabled GSK3 serine-phosphorylation may provide a valuable model to study bipolar disorder. PMID- 20357758 TI - Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT. AB - Gamma-aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy. Two of the GAD1 SNPs (rs1978340 (p=0.005) and rs769390 (p=0.004)) showed effects on GABA levels as did COMT val158met (p=0.04). We then tested three SNPs in GAD1 (rs1978340, rs11542313, and rs769390) for interaction with COMT val158met based on previous clinical results. In this model, rs11542313 and COMT val158met showed significant main effects (p=0.001 and 0.003, respectively) and a trend toward a significant interaction (p=0.05). Interestingly, GAD1 risk alleles for schizophrenia were associated with higher GABA/Cre, and Val-Val homozygotes had high GABA/Cre levels when on a GAD1 risk genotype background (N=6). These results support the importance of genetic variation in GAD1 and COMT in regulating prefrontal cortical GABA function. The directionality of the effects, however, is inconsistent with earlier evidence of decreased GABA activity in schizophrenia. PMID- 20357759 TI - Paroxetine-induced increase in activity of locus coeruleus neurons in adolescent rats: implication of a countertherapeutic effect of an antidepressant. AB - The concern that antidepressant (AD) drugs, especially selective serotonin reuptake inhibitors and paroxetine (PAR) in particular, can increase suicidality during the early treatment of juvenile patients (children and adolescents) has created a dilemma for clinicians treating depressives. Although preclinical research cannot resolve controversy in this area, our present findings may provide insight into how AD drugs might, under certain conditions, exacerbate rather than ameliorate the depressive state. Both clinical and preclinical evidences indicate that the principal noradrenergic cell group in the brain, the locus coeruleus (LC), is overactive in depressives and that, conversely, effective AD treatments decrease the activity of LC neurons. We report here that short-term (2 and 4 days) administration of PAR produces an increase in the activity of LC neurons (spontaneous firing rate and sensory-evoked responses) in young rats, contrary to the 'therapeutic' decrease in activity typically observed in adult rats. Blood levels of PAR were lower in young rats than in adult rats, although similar low blood levels produced by a lower dose of PAR in adult rats failed to produce an increase in LC activity. In addition, activity of young rats in the swim test was determined to assess depressive-like responses. The same dose/durations of PAR, which produced the largest increases in LC activity in young rats, produced decreases in swim-test activity, indicating that brief administration of PAR in young rats can promote, rather than reduce, the depressive state. These results offer a model that may help screen potential adjunctive treatments to avoid early adverse effects of ADs. PMID- 20357760 TI - Noradrenergic alpha1 receptors as a novel target for the treatment of nicotine addiction. AB - Nicotine is the main psychoactive ingredient in tobacco and its rewarding effects are considered primarily responsible for persistent tobacco smoking and relapse. Although dopamine has been extensively implicated in the rewarding effects of nicotine, noradrenergic systems may have a larger role than previously suspected. This study evaluated the role of noradrenergic alpha(1) receptors in nicotine and food self-administration and relapse, nicotine discrimination, and nicotine induced dopamine release in the nucleus accumbens in rats. We found that the noradrenergic alpha(1) receptor antagonist prazosin (0.25-1 mg/kg) dose dependently reduced the self-administration of nicotine (0.03 mg/kg), an effect that was maintained over consecutive daily sessions; but did not reduce food self administration. Prazosin also decreased reinstatement of extinguished nicotine seeking induced by either a nicotine prime (0.15 mg/kg) or nicotine-associated cues, but not food-induced reinstatement of food-seeking, and decreased nicotine induced (0.15 mg/kg) dopamine release in the nucleus accumbens shell. However, prazosin did not have nicotine-like discriminative effects and did not alter the dose-response curve for nicotine discrimination. These findings suggest that stimulation of noradrenergic alpha(1) receptors is involved in nicotine self administration and relapse, possibly via facilitation of nicotine-induced activation of the mesolimbic dopaminergic system. The findings point to alpha(1) adrenoceptor blockade as a potential new approach to the treatment of tobacco dependence in humans. PMID- 20357761 TI - Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study. AB - Preclinical studies suggest that lithium may exert neurotrophic effects that counteract pathological processes in the brain of patients with bipolar disorder (BD). To describe and compare the course and magnitude of gray matter volume changes in patients with BD who are treated with lithium or valproic acid (VPA) compared to healthy comparison subjects, and to assess clinical relationships to gray matter volume changes induced by lithium in patients with BD, we conducted longitudinal brain imaging and clinical evaluations of treatment response in 22 mood-stabilizing and antipsychotic medications-naive patients with BD who were randomly assigned to either lithium or VPA treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10-12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium. PMID- 20357763 TI - Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. AB - We performed a feasibility study to determine the optimal dosage and time of administration of the monoclonal antibody zirconium-89 ((89)Zr)-trastuzumab to enable positron emission tomography (PET) imaging of human epidermal growth factor receptor 2 (HER2)-positive lesions. Fourteen patients with HER2-positive metastatic breast cancer received 37 MBq of (89)Zr-trastuzumab at one of three doses (10 or 50 mg for those who were trastuzumab-naive and 10 mg for those who were already on trastuzumab treatment). The patients underwent at least two PET scans between days 2 and 5. The results of the study showed that the best time for assessment of (89)Zr-trastuzumab uptake by tumors was 4-5 days after the injection. For optimal PET-scan results, trastuzumab-naive patients required a 50 mg dose of (89)Zr-trastuzumab, and patients already on trastuzumab treatment required a 10 mg dose. The accumulation of (89)Zr-trastuzumab in lesions allowed PET imaging of most of the known lesions and some that had been undetected earlier. The relative uptake values (RUVs) (mean +/- SEM) were 12.8 +/- 5.8, 4.1 +/- 1.6, and 3.5 +/- 4.2 in liver, bone, and brain lesions, respectively, and 5.9 +/- 2.4, 2.8 +/- 0.7, 4.0 +/- 0.7, and 0.20 +/- 0.1 in normal liver, spleen, kidneys, and brain tissue, respectively. PET scanning after administration of (89)Zr-trastuzumab at appropriate doses allows visualization and quantification of uptake in HER2-positive lesions in patients with metastatic breast cancer. PMID- 20357762 TI - Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection. AB - Pigtail macaques (PTMs) rapidly progress to AIDS after simian immunodeficiency virus (SIV) infection. Given the strong association between human immunodeficiency virus (HIV) and SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTMs. We found that before SIV infection, PTMs had high levels of microbial translocation that correlated with significant damage to the structural barrier of the gastrointestinal tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of interleukin-17 producing T cells. These data highlight the relationship among mucosal damage, microbial translocation and systemic immune activation in the absence of SIV replication, and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTMs. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation. PMID- 20357765 TI - Atom-chip-based generation of entanglement for quantum metrology. AB - Atom chips provide a versatile quantum laboratory for experiments with ultracold atomic gases. They have been used in diverse experiments involving low dimensional quantum gases, cavity quantum electrodynamics, atom-surface interactions, and chip-based atomic clocks and interferometers. However, a severe limitation of atom chips is that techniques to control atomic interactions and to generate entanglement have not been experimentally available so far. Such techniques enable chip-based studies of entangled many-body systems and are a key prerequisite for atom chip applications in quantum simulations, quantum information processing and quantum metrology. Here we report the experimental generation of multi-particle entanglement on an atom chip by controlling elastic collisional interactions with a state-dependent potential. We use this technique to generate spin-squeezed states of a two-component Bose-Einstein condensate; such states are a useful resource for quantum metrology. The observed reduction in spin noise of -3.7 +/- 0.4 dB, combined with the spin coherence, implies four partite entanglement between the condensate atoms; this could be used to improve an interferometric measurement by -2.5 +/- 0.6 dB over the standard quantum limit. Our data show good agreement with a dynamical multi-mode simulation and allow us to reconstruct the Wigner function of the spin-squeezed condensate. The techniques reported here could be directly applied to chip-based atomic clocks, currently under development. PMID- 20357764 TI - Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. AB - Adiponectin is an anti-diabetic adipokine. Its receptors possess a seven transmembrane topology with the amino terminus located intracellularly, which is the opposite of G-protein-coupled receptors. Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes. PMID- 20357766 TI - The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness. AB - The T-cell receptor (TCR) interacts with peptide-major histocompatibility complexes (pMHC) to discriminate pathogens from self-antigens and trigger adaptive immune responses. Direct physical contact is required between the T cell and the antigen-presenting cell for cross-junctional binding where the TCR and pMHC are anchored on two-dimensional (2D) membranes of the apposing cells. Despite their 2D nature, TCR-pMHC binding kinetics have only been analysed three dimensionally (3D) with a varying degree of correlation with the T-cell responsiveness. Here we use two mechanical assays to show high 2D affinities between a TCR and its antigenic pMHC driven by rapid on-rates. Compared to their 3D counterparts, 2D affinities and on-rates of the TCR for a panel of pMHC ligands possess far broader dynamic ranges that match that of their corresponding T-cell responses. The best 3D predictor of response is the off-rate, with agonist pMHC dissociating the slowest. In contrast, 2D off-rates are up to 8,300-fold faster, with the agonist pMHC dissociating the fastest. Our 2D data suggest rapid antigen sampling by T cells and serial engagement of a few agonist pMHCs by TCRs in a large self pMHC background. Thus, the cellular environment amplifies the intrinsic TCR-pMHC binding to generate broad affinities and rapid kinetics that determine T-cell responsiveness. PMID- 20357767 TI - Nonlinear atom interferometer surpasses classical precision limit. AB - Interference is fundamental to wave dynamics and quantum mechanics. The quantum wave properties of particles are exploited in metrology using atom interferometers, allowing for high-precision inertia measurements. Furthermore, the state-of-the-art time standard is based on an interferometric technique known as Ramsey spectroscopy. However, the precision of an interferometer is limited by classical statistics owing to the finite number of atoms used to deduce the quantity of interest. Here we show experimentally that the classical precision limit can be surpassed using nonlinear atom interferometry with a Bose-Einstein condensate. Controlled interactions between the atoms lead to non-classical entangled states within the interferometer; this represents an alternative approach to the use of non-classical input states. Extending quantum interferometry to the regime of large atom number, we find that phase sensitivity is enhanced by 15 per cent relative to that in an ideal classical measurement. Our nonlinear atomic beam splitter follows the 'one-axis-twisting' scheme and implements interaction control using a narrow Feshbach resonance. We perform noise tomography of the quantum state within the interferometer and detect coherent spin squeezing with a squeezing factor of -8.2 dB (refs 11-15). The results provide information on the many-particle quantum state, and imply the entanglement of 170 atoms. PMID- 20357768 TI - Caspase activation precedes and leads to tangles. AB - Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death, severe cytological abnormalities, and markers of caspase activation and apoptosis, leading to the idea that tangles cause neurodegeneration in Alzheimer's disease and tau-related frontotemporal dementia. However, using in vivo multiphoton imaging to observe tangles and activation of executioner caspases in living tau transgenic mice (Tg4510 strain), we find the opposite: caspase activation occurs first, and precedes tangle formation by hours to days. New tangles form within a day. After a new tangle forms, the neuron remains alive and caspase activity seems to be suppressed. Similarly, introduction of wild-type 4-repeat tau (tau-4R) into wild-type animals triggered caspase activation, tau truncation and tau aggregation. Adeno-associated virus mediated expression of a construct mimicking caspase-cleaved tau into wild-type mice led to the appearance of intracellular aggregates, tangle-related conformational- and phospho-epitopes, and the recruitment of full-length endogenous tau to the aggregates. On the basis of these data, we propose a new model in which caspase activation cleaves tau to initiate tangle formation, then truncated tau recruits normal tau to misfold and form tangles. Because tangle bearing neurons are long-lived, we suggest that tangles are 'off pathway' to acute neuronal death. Soluble tau species, rather than fibrillar tau, may be the critical toxic moiety underlying neurodegeneration. PMID- 20357769 TI - Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity. AB - Strategies to combat HIV-1 require structural knowledge of envelope proteins from viruses in HIV-1 clade C, the most rapidly spreading subtype in the world. We present a crystal structure containing a clade C gp120 envelope. The structure, a complex between gp120, the host receptor CD4 and the CD4-induced antibody 21c, reveals that the 21c epitope involves contacts with gp120, a nonself antigen, and with CD4, an autoantigen. Binding studies using wild-type and mutant CD4 show that 21c Fab binds CD4 in the absence of gp120, and that binding of 21c to clade C and HIV-2 gp120s requires the crystallographically observed 21c-CD4 interaction. Additional binding data suggest a role for the gp120 V1V2 loop in creating a high-affinity, but slow-forming, epitope for 21c after CD4 binds. These results contribute to a molecular understanding of CD4-induced antibodies and provide the first visualization to our knowledge of a potentially autoreactive antibody Fab complexed with both self and nonself antigens. PMID- 20357770 TI - A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain. AB - Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody mimic (or 'monobody'), termed HA4, that bound to the Abelson (Abl) kinase SH2 domain with low nanomolar affinity. SH2 protein microarray analysis and MS of intracellular HA4 interactors showed HA4's specificity, and a crystal structure revealed how this specificity is achieved. HA4 disrupted intramolecular interactions of Abl involving the SH2 domain and potently activated the kinase in vitro. Within cells, HA4 inhibited processive phosphorylation activity of Abl and also inhibited STAT5 activation. This work provides a design guideline for highly specific and potent inhibitors of a protein interaction domain and shows their utility in mechanistic and cellular investigations. PMID- 20357771 TI - Structural characterization of a capping protein interaction motif defines a family of actin filament regulators. AB - Capping protein (CP) regulates actin dynamics by binding the barbed ends of actin filaments. Removal of CP may be one means to harness actin polymerization for processes such as cell movement and endocytosis. Here we structurally and biochemically investigated a CP interaction (CPI) motif present in the otherwise unrelated proteins CARMIL and CD2AP. The CPI motif wraps around the stalk of the mushroom-shaped CP at a site distant from the actin-binding interface, which lies on the top of the mushroom cap. We propose that the CPI motif may act as an allosteric modulator, restricting CP to a low-affinity, filament-binding conformation. Structure-based sequence alignments extend the CPI motif-containing family to include CIN85, CKIP-1, CapZIP and a relatively uncharacterized protein, WASHCAP (FAM21). Peptides comprising these CPI motifs are able to inhibit CP and to uncap CP-bound actin filaments. PMID- 20357772 TI - Crystal structure of the carnitine transporter and insights into the antiport mechanism. AB - CaiT is a membrane antiporter that catalyzes the exchange of L-carnitine with gamma-butyrobetaine across the Escherichia coli membrane. To obtain structural insights into the antiport mechanism, we solved the crystal structure of CaiT at a resolution of 3.15 A. We crystallized CaiT as a homotrimer complex, in which each protomer contained 12 transmembrane helices and 4 l-carnitine molecules outlining the transport pathway across the membrane. Mutagenesis studies revealed a primary binding site at the center of the protein and a secondary substrate binding site at the bottom of the intracellular vestibule. These results, together with the insights obtained from structural comparison with structurally homologous transporters, provide mechanistic insights into the association between substrate translocation and the conformational changes of CaiT. PMID- 20357773 TI - Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis. AB - Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNP-specific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs). Here we show that depletion of coilin in zebrafish embryos leads to CB dispersal, deficits in snRNP biogenesis and expression of spliced mRNA, as well as reduced cell proliferation followed by developmental arrest. Notably, injection of purified mature human snRNPs restored mRNA expression and viability. snRNAs were necessary but not sufficient for rescue, showing that only assembled snRNPs can bypass the requirement for coilin. Thus, coilin's essential function in embryos is to promote macromolecular assembly of snRNPs, likely by concentrating snRNP components in CBs to overcome rate-limiting assembly steps. PMID- 20357774 TI - Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. AB - Telomerase is a specialized DNA polymerase that extends the 3' ends of eukaryotic linear chromosomes, a process required for genomic stability and cell viability. Here we present the crystal structure of the active Tribolium castaneum telomerase catalytic subunit, TERT, bound to an RNA-DNA hairpin designed to resemble the putative RNA-templating region and telomeric DNA. The RNA-DNA hybrid adopts a helical structure, docked in the interior cavity of the TERT ring. Contacts between the RNA template and motifs 2 and B' position the solvent accessible RNA bases close to the enzyme active site for nucleotide binding and selectivity. Nucleic acid binding induces rigid TERT conformational changes to form a tight catalytic complex. Overall, TERT-RNA template and TERT-telomeric DNA associations are remarkably similar to those observed for retroviral reverse transcriptases, suggesting common mechanistic aspects of DNA replication between the two families of enzymes. PMID- 20357775 TI - The Hox genes and their roles in oncogenesis. AB - Hox genes, a highly conserved subgroup of the homeobox superfamily, have crucial roles in development, regulating numerous processes including apoptosis, receptor signalling, differentiation, motility and angiogenesis. Aberrations in Hox gene expression have been reported in abnormal development and malignancy, indicating that altered expression of Hox genes could be important for both oncogenesis and tumour suppression, depending on context. Therefore, Hox gene expression could be important in diagnosis and therapy. PMID- 20357776 TI - Safer CARS. PMID- 20357779 TI - Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. PMID- 20357780 TI - Designer lipids advance systemic siRNA delivery. PMID- 20357781 TI - AAV provides an alternative for gene therapy of the peripheral sensory nervous system. PMID- 20357783 TI - Pain by name, pain by nature. PMID- 20357785 TI - Acute inflammatory arthritis: are glucocorticoids of benefit in very early arthritis? PMID- 20357786 TI - Therapy: Surgery or nonsurgical therapy for carpal tunnel syndrome? PMID- 20357787 TI - Autoimmunity: effectiveness of treatments for pregnant women with APS. PMID- 20357788 TI - Adverse effects of chronic opioid therapy for chronic musculoskeletal pain. AB - The use of opioids for the treatment of chronic pain has increased dramatically over the past decade. Whether these drugs provide considerable benefits in terms of pain reduction and improved function to balance the risks associated with their use, however, is unclear. Of particular importance to clinicians treating chronic musculoskeletal pain is opioid-induced hyperalgesia, the activation of pronociceptive pathways by exogenous opioids that results in central sensitization to pain. This phenomenon results in an increase in pain sensitivity and can potentially exacerbate pre-existing pain. Opioids also have powerful positive effects on the reward and reinforcing circuits of the brain that might lead to continued drug use, even if there is no abuse or misuse. The societal risk of increased opioid prescription is associated with increased nonmedical use, serious adverse events and death. Patients with chronic musculoskeletal pain should avoid the long-term use of opioids unless the benefits are determined to outweigh risks, in which case, the use of chronic opioids should be regularly re evaluated. PMID- 20357789 TI - Self-management of chronic low back pain and osteoarthritis. AB - Chronic low back pain and osteoarthritis are two musculoskeletal problems that are highly prevalent in the general population, are frequently episodic and persistent, and are associated with high costs to society, both direct and indirect. This epidemiological picture provides the background that justifies the use of self-management strategies in managing these problems. For this Review, relevant systematic reviews were included that related to effectiveness; other study designs were included that addressed other aspects of the topic. The accepted definition of self-management includes liaison between health professionals and individuals with these problems, as well as independent health promotion activities. Independent self-management strategies, such as exercise and self-medication, are practiced by individuals in the general population. Consistent evidence shows that self-management programs for osteoarthritis are effective in addressing pain and function, but effect sizes are small and might be clinically negligible. Educational programs for patients with back pain are effective in an occupational setting and if combined with an exercise program. Exercise is an effective strategy in the management of both chronic low back pain and osteoarthritis, although it is unclear what the optimum exercise is. Exercise, supported by advice and education, should be at the core of self management strategies for chronic low back pain and osteoarthritis. PMID- 20357790 TI - Psychological approaches to understanding and treating arthritis pain. AB - Arthritis pain has traditionally been evaluated from a biomedical perspective, but there is increasing evidence that psychological factors have an important role in patients' adjustment to arthritis pain. The evolution of pain theories has led to the development of models, such as the cognitive-behavioral model, which recognize the potential involvement of psychological factors in pain. Emotional, cognitive, behavioral and social context variables are useful in understanding pain in patients with arthritis, and have led to the development of psychological approaches for treating arthritis pain. These include pain coping skills training, interventions that include patients' partners, and emotional disclosure strategies. PMID- 20357792 TI - The role of the rheumatologist in managing pain therapy. AB - Despite the clinical importance of pain in patients with rheumatic diseases, rheumatologists have not delegated a proportionate amount of effort to its investigation and treatment. Some of the assumptions that have hindered progress in pain management for rheumatologists include a preference for immunologic research over pain research, a reluctance to provide opioid therapy, and inadequate compensation. Contrary to these assumptions, pain management is becoming an area of increasing research and clinical effort in the field of rheumatology. This article discusses how the barriers to effective pain management can be overcome, although the relative differential compensation for psychosocial versus interventional therapy remains a concern. In the future, rheumatologists will need to expend greater time and effort in the study of pain management to remain pertinent to the needs of their rheumatic disease patients. PMID- 20357793 TI - Kinase inhibitors attract attention as oral rheumatoid arthritis drugs. PMID- 20357795 TI - Trial watch: Phase III success for novel Clostridium difficile antibiotic. PMID- 20357791 TI - Surgical options for patients with shoulder pain. AB - Shoulder pain is a common musculoskeletal complaint in the community, which can arise from diverse causes. Regardless of the cause, mild cases can often be effectively treated conservatively, with options including rest, physiotherapy, pain relief and glucocorticoid injections. If conservative strategies fail after a 3-6 month period then surgery might be considered. Generally, the proportion of patients with shoulder pain who require surgery is small. When surgery is considered, a clear diagnosis and structural information from imaging are required. The indications for surgery, and success rate, depend on the specific diagnosis as well as on the individual clinical presentation. Evidence from case series suggest that surgical interventions for shoulder pain are effective when used appropriately. This article outlines the surgical management of the most common painful conditions that affect the shoulder, including impingement, rotator cuff tear, frozen shoulder, osteoarthritis, rheumatoid arthritis and calcific tendonitis. PMID- 20357796 TI - Trial watch: NeuroSearch's dopaminergic stabilizer improves movement disorders in Huntington's disease. PMID- 20357797 TI - Market watch: key clinical and regulatory events in Q2 2010. PMID- 20357799 TI - An audience with...Margaret Anderson. PMID- 20357800 TI - The anticonvulsants market. PMID- 20357801 TI - Liraglutide. AB - In January 2010, liraglutide (Victoza; Novo Nordisk)--an injectable glucagon-like peptide 1 receptor agonist--was approved by the US FDA to improve glycaemic control in adults with type 2 diabetes mellitus. PMID- 20357802 TI - Virtual screening: an endless staircase? AB - Computational chemistry--in particular, virtual screening--can provide valuable contributions in hit- and lead-compound discovery. Numerous software tools have been developed for this purpose. However, despite the applicability of virtual screening technology being well established, it seems that there are relatively few examples of drug discovery projects in which virtual screening has been the key contributor. Has virtual screening reached its peak? If not, what aspects are limiting its potential at present, and how can significant progress be made in the future? PMID- 20357804 TI - In memoriam: Minoru Tomita, MD, PhD, 1934-2010. PMID- 20357805 TI - Mcl1 becomes ubiquitin-ous: new opportunities to antagonize a pro-survival protein. PMID- 20357803 TI - Carbohydrate vaccines: developing sweet solutions to sticky situations? AB - Recent technological advances in glycobiology and glycochemistry are paving the way for a new era in carbohydrate vaccine design. This is enabling greater efficiency in the identification, synthesis and evaluation of unique glycan epitopes found on a plethora of pathogens and malignant cells. Here, we review the progress being made in addressing challenges posed by targeting the surface carbohydrates of bacteria, protozoa, helminths, viruses, fungi and cancer cells for vaccine purposes. PMID- 20357806 TI - Mad revival of cancer. PMID- 20357807 TI - Divalent metal transporter, iron, and Parkinson's disease: a pathological relationship. PMID- 20357808 TI - Validity of neonatal jaundice evaluation by primary health-care workers and physicians in Karachi, Pakistan. AB - OBJECTIVE: The purpose of this study was to validate primary health-care workers' and physicians' visual assessment of neonatal hyperbilirubinemia in Karachi, Pakistan. STUDY DESIGN: We compared primary health-care workers' and physicians' clinical identification of jaundice in infants <60 days old. RESULT: Primary health-care workers identified 1- to 20-day-old neonates with hyperbilirubinemia > or =15 mg per 100 ml (260 micromol l(-1)) with 83.3% sensitivity and 50.5% specificity; neonates aged 1 to 6 days were identified with 76.2% sensitivity and 60.7% specificity. Physicians identified neonates aged 1 to 20 days with hyperbilirubimemia > or =15 mg per 100 ml (260 micromol l(-1)) with 51.4% sensitivity and 90.7% specificity, and neonates aged 1 to 6 days with 50% sensitivity and 88.5 % specificity. The primary health-care workers' and physicians' assessments showed fair interobserver agreement (kappa statistic 0.29). CONCLUSION: Primary health-care workers identified hyperbilirubinemic neonates with adequate sensitivity. With proper training and supervision, their assessment could improve the referral of hyperbilirubinemic neonates in low resource settings in the developing world. PMID- 20357809 TI - Perinatal predictors of outcome in gastroschisis. AB - OBJECTIVE: To identify perinatal risk variables predictive of outcome in gastroschisis. STUDY DESIGN: Gastroschisis cases were collected over a 3-year period from a national database. Risk variables evaluated included gestational age (GA), birth weight, time of birth, admission illness severity (score for neonatal acute physiology-II, SNAP-II) score, and abdominal closure type. Mortality and survival outcomes were analyzed. Multivariate analyses were performed. RESULT: In all, 239 infants were survived (96%). SNAP-II score predicted mortality (relative risk (RR)=1.07, 95% confidence interval (CI)=1.0 to 1.1). Length of hospital stay (LOS) and ventilation days were predicted by GA and by SNAP-II score. SNAP-II score predicted total parenteral nutrition (TPN) days (P=0.006). Severe cholestasis (conjugated bilirubin of >10 mg per 100 ml) was inversely related to GA (RR=0.77, 95% CI=0.61 to 0.97) and directly to categorical SNAP-II score (RR=3.4, 95% CI=1.2 to 10.1). Urgent closure predicted fewer TPN days (P=0.003) and shorter LOS (P=0.0002). CONCLUSION: SNAP-II scores significantly predict mortality and survival outcomes. Urgent closure favors fewer TPN days and shorter LOS. Our data refute routine preterm delivery in gastroschisis. PMID- 20357810 TI - Tele-education vs classroom training of neonatal resuscitation: a randomized trial. AB - OBJECTIVE: To compare gain in knowledge and skills of neonatal resuscitation using tele-education instruction vs conventional classroom teaching. STUDY DESIGN: This randomized controlled trial was conducted in the tele-education facility of a tertiary care center. In-service staff nurses were randomized to receive training by tele-education instruction (TI, n=26) or classroom teaching (CT, n=22) method from two neonatology instructors using a standardized teaching module on neonatal resuscitation. Gain in knowledge and skill scores of neonatal resuscitation were measured using objective assessment methods. RESULT: Age, educational qualification and professional experience of the participants in two groups were comparable. Pre-training mean knowledge scores were higher in TI group (8.3+/-1.7 vs 6.6+/-1.4, P=0.004). However, skill scores were comparable in the two groups (11.7+/-3 vs 10.3+/-2.9, P=0.13). Training resulted in a significant and comparable gain in knowledge scores (4.2+/-2.2 vs 5.3+/-1.7; P=0.06) and skills scores (4.5+/-3.3 vs 5.0+/-3.1, P=0.62) in both the groups. The post-training knowledge scores (TI: 12.5+/-1.7 vs CT: 12.0+/-1.7, P=0.37) and the post-training skill scores (TI: 16.0+/-0.5 vs CT: 15.6+/-2.5, P=0.55) were comparable in the two groups. However, the post-training scores, adjusted for baseline knowledge scores, were statistically higher in the in-person group compared with the telemedicine group (knowledge: 12.46+/-0.03 vs 12.16+/-0.01, P=0.00; skills: 15.6+/-2.5 vs 16.0+/-2.8, P=0.00). The quantum of lower scores in the telemedicine group was only 2% for knowledge and 6% for skills. This difference was felt to be of only marginal importance. Satisfaction scores among trainees and instructors were comparable in the two groups. CONCLUSION: Tele education offers a feasible and effective alternative to conventional training in neonatal resuscitation among health-care providers. PMID- 20357811 TI - Clinical characterization and long-term prognosis of neurological development in preterm infants with late-onset circulatory collapse. AB - OBJECTIVE: To characterize the risk factors for late-onset circulatory collapse (LCC) in preterm infants responsive to corticosteroid therapy and evaluate the long-term neurological prognosis. STUDY DESIGN: A retrospective case-control study for preterm infants (<=32 weeks' gestation) admitted to our neonatal intensive care unit from 1994 through 2002. RESULT: Sixty-five infants (11%) were diagnosed with LCC. Infants with a shorter gestation and lower birth weight had a higher incidence of LCC. LCC infants had a significantly lower 1-min Apgar score, significantly higher incidence of severe intraventricular hemorrhage, chronic lung disease, and postnatal periventricular leukomalacia, and significantly longer duration of ventilation use, oxygen use, and hospital stay. Somatic growth at 36 weeks' postmenstrual age was poorer in infants with LCC than without LCC (controls). LCC infants were significantly more likely than controls to have cerebral palsy at 3 years. CONCLUSION: LCC is associated with poor neurodevelopmental outcomes. Prevention of LCC can lead to improved neurological prognoses. PMID- 20357813 TI - Revertant mosaicism in recessive dystrophic epidermolysis bullosa. PMID- 20357812 TI - Functional modulation of IGF-binding protein-3 expression in melanoma. AB - IGF-binding protein-3 (IGFBP3) is a member of the IGFBP family, which regulates mitogenic and antiapoptotic effects of IGFs. In this report we evaluated the role of IGFBP3 in melanoma. Quantitative real-time PCR (qRT-PCR), western blot, and ELISA analyses indicated a significant downregulation of IGFBP3 expression in melanoma cell lines as compared with a normal melanocyte cell line. Melanoma cell lines treated with the demethylating agent 5-AZA-2'-deoxycytidine reexpressed IGFBP3 at the mRNA and protein levels. Chromatin immunoprecipitation assays revealed enrichment of acetylated histones H3 and H4, and H3 di- and tri methylated lysine 4 on the unmethylated IGFBP3 promoter. The IGFBP3 promoter region was highly methylated in human melanoma samples as compared with normal nevi. Overexpression of IGFBP3 in melanoma cells in vitro suppressed tumor cell survival, induced apoptosis, reduced colony formation and invasion, and induced expression of the proapoptotic genes p21, PUMA, and BAX. IGFBP3 overexpression also resulted in cleavage of caspase 3 and reduced expression of phosphorylated AKT. Stable overexpression of IGFBP3 suppressed tumor cell growth in vivo. Our study results indicate that silencing of IGFBP3 in melanoma is due to the methylation of its promoter, and that overexpression of IGFBP3 induces apoptosis and suppresses cell survival and growth. PMID- 20357814 TI - Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis. AB - Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed. PMID- 20357815 TI - Cyclic AMP suppresses matrix metalloproteinase-1 expression through inhibition of MAPK and GSK-3beta. AB - Expression of matrix metalloproteinase-1 (MMP-1) is stimulated by diverse stimuli and is likely to be regulated by many signaling pathways. cAMP is known to act as a second messenger for various extracellular stimuli and to be involved in the regulation of cell proliferation, apoptosis, and inflammation. Here, we investigated the effect of cAMP on tumor necrosis factor (TNF)-alpha-induced MMP 1 expression and the molecular events involved in the processes in human skin fibroblasts. We showed that cAMP suppresses TNF-alpha-induced MMP-1 expression via protein kinase A (PKA) pathway. cAMP inhibited TNF-alpha-stimulated ERK and JNK activation, which was shown to have an important role in MMP-1 expression. However, MMP-1 expression could also be inhibited by cAMP even when ERK and JNK activities were unaffected, indicating that there might be other target(s) that mediate cAMP-mediated suppression of MMP-1 expression. Further studies revealed that glycogen synthase kinase (GSK)-3beta can be inactivated by cAMP/PKA pathway and has important roles in MMP-1 expression, and showed that inactivation of GSK 3beta is critical for suppression of MMP-1 expression by cAMP elevation after TNF alpha treatment. Taken together, our results suggest that cAMP/PKA pathway can suppress MMP-1 expression through inhibition of multiple signaling pathways, including MAPK and GSK-3beta. PMID- 20357816 TI - Canine follicle stem cell candidates reside in the bulge and share characteristic features with human bulge cells. AB - The hair follicle bulge has attracted great interest as a stem cell repository. Previous studies have focused on rodent or human bulge stem cells, and our understanding of those in other species is limited. In this study, we attempted to localize and characterize stem cell candidates in canine hair follicles. The canine skin xenografting study located label-retaining cells in the outer root sheath around the insertion point of the arrector pili muscle, where the immunoreactivity of human bulge markers, keratin 15 and follistatin, were detected. Canine bulge cell-enriched keratinocytes up-regulated human bulge biomarkers CD200 and DIO2, and conserved key cell regulators of bulge stem cells, such as SOX9 and LHX2. Importantly, canine bulge-derived keratinocytes were highly proliferative in vitro and, when combined with trichogenic dermal cells, reconstituted pilosebaceous structures as well as the epidermis in vivo. Successful detection of canine specific DNA sequences suggested that the regenerated tissue was of canine origin. In addition, canine specific bulge cell and sebocyte lineage markers were expressed in reconstituted pilosebaceous units, implying the multipotency of canine bulge cells. Our findings demonstrate a unique strategy utilizing canine bulge cells to investigate human stem cell biology and intractable hair disorders that involve the bulge region. PMID- 20357817 TI - MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. AB - Malignant cutaneous melanoma is a highly aggressive form of skin cancer. Despite improvements in early melanoma diagnosis, the 5-year survival rate remains low in advanced disease. Therefore, novel biomarkers are urgently needed to devise new means of detection and treatment. In this study, we aimed to improve our understanding of microRNA (miRNA) deregulation in melanoma development and their impact on patient survival. Global miRNA expression profiles of a set of melanoma lymph node metastases, melanoma cell lines, and melanocyte cultures were determined using Agilent array. Deregulated miRNAs were evaluated in relation with clinical characteristics, patient survival, and mutational status for BRAF and NRAS. Several miRNAs were differentially expressed between melanocytes and melanomas as well as melanoma cell lines. In melanomas, miR-193a, miR-338, and miR-565 were underexpressed in cases with a BRAF mutation. Furthermore, low expression of miR-191 and high expression of miR-193b were associated with poor melanoma-specific survival. In conclusion, our findings show miRNA dysregulation in malignant melanoma and its relation to established molecular backgrounds of BRAF and NRAS oncogenic mutations. The identification of an miRNA classifier for poor survival may lead to the development of miRNA detection as a complementary prognostic tool in clinical practice. PMID- 20357818 TI - HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta. AB - The regulation of CD44v6, a variant of the CD44 family of glycosylated adhesion molecules, through hepatocyte growth factor (HGF) has implications for motility in primary human melanocytes. We show that exposure of primary human melanocytes to HGF results in an increase of CD44v6 expression. Immunostaining of melanocytic lesions revealed low cytoplasmic positivity of CD44v6 in some nevi but high membranous expression in primary cutaneous melanomas, and cutaneous and lymph node metastases. HGF-dependent CD44v6 regulation in melanocytes is NF-kappaB dependent because BAY 11-7082, an inhibitor of NF-kappaB activation, but not interference with the mitogen-activated protein kinase or phosphatidylinositol 3 kinase cascade, antagonized HGF-induced CD44v6 expression. NF-kappaB-mediated transcriptional regulation of CD44v6 involves the transcription factors Egr-1 and CCAAT enhancer-binding protein-beta (C/EBP-beta). In gel shift assays, the initial binding of p100/p52 NF-kappaB, C/EBP-beta, and Egr-1 to the CD44 promoter experienced reshuffling toward increased affinity of C/EBP-beta after HGF stimulation. A blocking antibody to CD44v6 decreased HGF-induced c-Met phosphorylation as well as enhanced random- and site-directed migration. Our data show that HGF-induced motility in primary human melanocytes depends on c-Met CD44v6 interaction, and that HGF-enhanced CD44v6 expression is required for motility and transcriptional upregulation of CD44v6, presumably mediated through a complex comprising NF-kappaB/C/EBP-beta and Egr-1. PMID- 20357819 TI - A transgenic mouse for imaging caspase-dependent apoptosis within the skin. AB - Apoptosis is an essential process for the maintenance of normal physiology. The ability to noninvasively image apoptosis in living animals would provide unique insights into its role in normal and disease processes. Herein, a recombinant reporter consisting of beta-galactosidase gene flanked by two estrogen receptor regulatory domains and intervening Asp-Glu-Val-Glu sequences was constructed to serve as a tool for in vivo assessment of apoptotic activity. The results demonstrate that when expressed in its intact form, the hybrid reporter had undetectable beta-galactosidase activity. Caspase 3 activation in response to an apoptotic stimulus resulted in cleavage of the reporter, and thereby reconstitution of beta-galactosidase activity. Enzymatic activation of the reporter during an apoptotic event enabled noninvasive measurement of beta galactosidase activity in living cells, which correlated with traditional measures of apoptosis in a dose- and time-dependent manner. Using a near-infrared fluorescent substrate of beta-galactosidase (9H-{1,3-dichloro-9,9-dimethylacridin 2-one-7-yl} beta-D-galactopyranoside), noninvasive in vivo imaging of apoptosis was achieved in a xenograft tumor model in response to proapoptotic therapy. Finally, a transgenic mouse model was developed expressing the ER-LACZ-ER reporter within the skin. This reporter and transgenic mouse could serve as a unique tool for the study of apoptosis in living cells and animals, especially in the context of skin biology. PMID- 20357820 TI - The cleaning of photographic retractors; a survey, clinical and laboratory study. AB - OBJECTIVES: To determine the methods currently being used to decontaminate photographic retractors in specialist orthodontic practice and to investigate the effectiveness of the cleaning methods. DESIGN: The study was carried out in two parts: I - a postal self-report questionnaire, and II - a cross-sectional clinical and laboratory investigation. SETTING: The Orthodontic Department of the Charles Clifford Dental Hospital. SUBJECTS AND MATERIALS: I - The questionnaire was sent to 278 specialist UK orthodontists. II - One hundred and twenty pairs of photographic retractors were collected following use. One retractor from each pair was randomly chosen to be the unwashed control and immediately placed in 20 ml of PBS-Tween for elution. The other was subjected to the one of four cleaning procedures: alcohol wipe, handwashing, ultrasonic bath or washer-disinfector, before being placed in PBS-Tween. Aliquots were taken for assay. MAIN OUTCOME MEASURES: Antibody capture (ELISA) for amylase, to detect the presence of saliva, and for albumin, to detect the presence of serum. RESULTS: I - The questionnaire response rate was 65% and the majority of respondents (87.2%) were routinely taking clinical photographs. A wide variety of techniques were being used to decontaminate photographic retractors. II - All unwashed controls had detectable levels of amylase and albumin. All the retractors that were cleaned using an alcohol wipe had residual detectable levels of amylase and 80% had detectable levels of albumin. Only one retractor had detectable amylase and one had detectable albumin following cleaning using the washer-disinfector. There was a highly significant statistical difference between the techniques in the proportional reduction in both amylase and albumin detected from the unwashed control and cleaned experimental retractors (p <0.001). The infective risk from inadequate cleaning of photographic retractors is discussed. CONCLUSIONS: The washer-disinfector is the most effective method of cleaning photographic retractors, but no method was found to be 100% successful at removing amylase and albumin. PMID- 20357821 TI - Trisomy 11: prevalence among 22,403 unique patient cytogenetic studies and clinical correlates. PMID- 20357822 TI - AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. AB - Activation-induced cytidine deaminase (AID) diversifies immunoglobulin through somatic hypermutation (SHM) and class-switch recombination (CSR). AID-transgenic mice develop T-lymphoma, indicating that constitutive expression of AID leads to tumorigenesis. Here, we transplanted mouse bone marrow cells transduced with AID. Twenty-four of the 32 recipient mice developed T-lymphoma 2-4 months after the transplantation. Surprisingly, unlike AID-transgenic mice, seven recipients developed B-leukemia/lymphoma with longer latencies. None of the mice suffered from myeloid leukemia. When we used nude mice as recipients, they developed only B-leukemia/lymphoma, presumably due to lack of thymus. Analysis of AID mutants suggested that an intact form with SHM activity is required for maximum ability of AID to induce lymphoma. Except for a K-ras active mutant in one case, specific mutations could not be identified in T-lymphoma; however, Notch1 was constitutively activated in most cases. Importantly, truncations of Ebf1 or Pax5 were observed in B-leukemia/lymphoma. In conclusion, this is the first report on the potential of AID overexpression to promote B-cell lymphomagenesis in a mouse model. Aberrant expression of AID in bone marrow cells induced leukemia/lymphoma in a cell-lineage-dependent manner, mainly through its function as a mutator. PMID- 20357823 TI - CBL mutations in juvenile myelomonocytic leukemia and pediatric myelodysplastic syndrome. PMID- 20357824 TI - CD5+CD23+ leukemic cell populations in TCL1 transgenic mice show significantly increased proliferation and Akt phosphorylation. AB - B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia. Deregulation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene in mouse B cells causes a CD5-positive leukemia similar to aggressive human B-CLLs. We recently reported that levels of TCL1 expression in B-CLL are regulated by miR-29 and miR 181 that target 3' UTR of TCL1. To determine whether treatment with microRNAs targeting TCL1 can inhibit B-CLL in mice, we generated TCL1 transgenic mice using a construct containing the 3' and 5' UTRs of TCL1 under B-cell-specific Emicro promoter (Emicro-TCL1FL). At the age of 16-20 months, these mice showed B-CLL like disease. Immunophenotyping revealed accumulation of CD5+CD23+B220+ population in spleens and lymph nodes. Our results show that CD5+CD23+ B-cell populations from Emicro-TCL1FL mice actively proliferate and show significantly increased levels of phospho-Akt. Emicro-TCL1FL mice showed immunological abnormalities similar to human B-CLL, including hypoimmunoglobulinemia, abnormal levels of cytokines and impaired immune response. These findings revealed biochemical and immunological similarities between Tcl1-driven B-CLL in mice and human B-CLL. PMID- 20357825 TI - MSK1 activation in acute myeloid leukemia cells with FLT3 mutations. PMID- 20357826 TI - EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia. AB - Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1+), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1+ using gene expression profiling and RQ-PCR. EVI1+ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLL-rearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1+ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1+ and EVI1- pediatric AML were observed (28%+/-11 vs 44%+/-4, P=0.04), multivariate analysis did not identify EVI1+ as an independent prognostic factor. We conclude that EVI1+ can be found in approximately 10% of pediatric AML. Although EVI1+ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1+ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1+ pediatric AML. PMID- 20357829 TI - Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model. AB - Foxp3, a member of the forkhead transcription factor family, is a master gene that controls the development and function of CD4(+)CD25(+) regulatory T (Treg) cells. It is thought to contribute to pathogenesis of many different tumors, including ovarian carcinoma and pancreatic, breast and pancreatic ductal adenocarcinoma. Selectively depleted Foxp3-expressing cells with anit-CD25 antibodies or vaccination of Foxp3 mRNA-transfected dendritic cells engender protective immunity against tumor. This study targeted silencing Foxp3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector to evaluate the therapeutic role of Foxp3 short-hairpin RNAs (shRNAs) in a murine model of leukemia. RLmale symbol1, a mouse CD4(+)CD25(+) leukemia cell with Foxp3 expression, was used as the leukemia animal model. By infecting RLmale symbol1 cells with Lenti-Foxp3-siRNA, we reduced Foxp3 gene expression and the suppressive function of CD4(+)CD25(-) effector cells stimulated with ConA. Moreover, lentiviral-mediated Foxp3 RNAi transduced into RLmale symbol1 cell or injected into the tumor showed suppressive effects on tumor growth and prolonged the survival of tumor-transplanted mice. However, this suppressive effect was abrogated in NOD-SCID mice transplanted with Lenti-Foxp3-siRNA-infected RLmale symbol1 cells. In conclusion, inhibiting Foxp3 gene expression by shRNAs effectively decreases tumor growth of Treg cell-like leukemia. The results may provide a novel strategy for future immunotherapy against cancers. PMID- 20357828 TI - IL-10 delivery by AAV5 vector attenuates inflammation in mice with Pseudomonas pneumonia. AB - Lung infections with Pseudomonas aeruginosa and other pathogens in cystic fibrosis (CF) cause progressive airway obstruction and tissue damage, the predominant cause of morbidity and mortality in CF. We investigated whether a recombinant adeno-associated virus type 5 (AAV5) vector expressing murine interleukin (IL)-10 (AAV5.Cbeta-mIL-10), a regulatory/anti-inflammatory cytokine, could decrease airway inflammation in IL-10 knockout mice chronically infected with mucoid P. aeruginosa. Mice that received AAV5.Cbeta-mIL10 through intratracheal inoculation produced IL-10 at an average of 25 000 pg/ml in the epithelial lining fluid (ELF) and 12 000 pg/g-lung tissue 6 weeks post-vector delivery, significantly higher levels than in placebo-treated mice. At 3 days post-infection, proinflammatory cytokines (IL-1beta, tumor necrosis factor (TNF) alpha, macrophage inhibitory protein (MIP)-1alpha and (KC) in the ELF and lung homogenate were decreased (1-9 folds) in the AAV5.Cbeta-mIL10-treated mice accompanied by less pronounced and more localized neutrophil infiltration in lung sections, when compared with placebo-treated mice. These results suggest that AAV5.Cbeta-mIL10 induces IL-10 levels in the lungs mediating a significant anti inflammatory response and making AAV-IL-10 gene transfer a potentially useful therapy in the treatment of CF lung disease. PMID- 20357827 TI - Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. AB - The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs. PMID- 20357830 TI - Generation of human TRIM5alpha mutants with high HIV-1 restriction activity. AB - Rhesus macaque tripartite motif (TRIM)5alpha potently inhibits early stages of human immunodeficiency virus (HIV)-1 replication, while the human orthologue has little effect on this virus. We used PCR-based random mutagenesis to construct a large library of human TRIM5alpha variants containing mutations in the PRYSPRY domain. We then applied a functional screen to isolate human cells made resistant to HIV-1 infection by the expression of a mutated TRIM5alpha. This protocol led to the characterization of a human TRIM5alpha variant containing a mutation at arginine 335 as conferring resistance to HIV-1 infection. The level of protection stemming from expression of this mutant was comparable to that of previously described mutations at position 332. R332/R335 double mutants decreased permissiveness to HIV-1 and to other lentiviruses by 20- to 50-fold in TE671 fibroblasts and in the T-cell line SUP-T1, and prevented HIV-1 spreading infection as efficiently as the rhesus macaque TRIM5alpha orthologue did. The finding that only two substitutions in human TRIM5alpha can confer resistance to HIV-1 at levels as high as one of the most potent natural orthologues of TRIM5alpha removes a roadblock toward the use of this restriction factor in human gene therapy applications. PMID- 20357832 TI - Further limitations of phylogenetic group-specific probes used for detection of bacteria in environmental samples. PMID- 20357831 TI - Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10(+)IFN-gamma(+)CD4(+) T cells. AB - Asthma is characterized by allergen-induced airway inflammation orchestrated by Th2 cells. Dendritic cells (DCs) were found to efficiently prime naive T-helper cells. Thus, modification of DC function may be used as an ideal tool to treat allergic asthma by changing CD4(+) T-cell differentiation or suppressing Th2 development. In this study, we examined whether a DC-based vaccine can be applied to DCs modified with interleukin (IL)-10- and IL-12-expressing adenoviruses to prevent ovalbumin (OVA)-induced asthma in mice. Herein, we show that these modified DCs efficiently moderated the characteristics of asthma, including expressions of OVA-specific antibodies, airway hyperresponsiveness, eosinophilic airway inflammation, and Th2 cytokines production. Additionally, IL-10 and IL-12 gene-modified DCs enhanced the development of both T-helper type 1 (Th1) and IL 10(+)IFN-gamma(+) (interferon-gamma) double-positive T cells in vivo. In vitro generated OVA-specific IL-10(+)IFN-gamma(+)CD4(+) T cells inhibited the proliferation of naive CD4(+) T cells, and this suppressive effect was a cell contact-dependent mechanism. Furthermore, we showed that combined cytokine modulated DCs could alleviate established allergic airway inflammation. Taken together, these results suggest that IL-10 and IL-12 gene-modulated DCs are effective in suppressing asthmatic airway inflammation through both immune deviation and immune suppression and are a potential therapeutic approach for asthma. PMID- 20357833 TI - Mesoscale eddies: hotspots of prokaryotic activity and differential community structure in the ocean. AB - To investigate the effects of mesoscale eddies on prokaryotic assemblage structure and activity, we sampled two cyclonic eddies (CEs) and two anticyclonic eddies (AEs) in the permanent eddy-field downstream the Canary Islands. The eddy stations were compared with two far-field (FF) stations located also in the Canary Current, but outside the influence of the eddy field. The distribution of prokaryotic abundance (PA), bulk prokaryotic heterotrophic activity (PHA), various indicators of single-cell activity (such as nucleic acid content, proportion of live cells, and fraction of cells actively incorporating leucine), as well as bacterial and archaeal community structure were determined from the surface to 2000 m depth. In the upper epipelagic layer (0-200 m), the effect of eddies on the prokaryotic community was more apparent, as indicated by the higher PA, PHA, fraction of living cells, and percentage of active cells incorporating leucine within eddies than at FF stations. Prokaryotic community composition differed also between eddy and FF stations in the epipelagic layer. In the mesopelagic layer (200-1000 m), there were also significant differences in PA and PHA between eddy and FF stations, although in general, there were no clear differences in community composition or single-cell activity. The effects on prokaryotic activity and community structure were stronger in AE than CE, decreasing with depth in both types of eddies. Overall, both types of eddies show distinct community compositions (as compared with FF in the epipelagic), and represent oceanic 'hotspots' of prokaryotic activity (in the epi- and mesopelagic realms). PMID- 20357835 TI - Identification and transcriptional analysis of trans-DCE-producing reductive dehalogenases in Dehalococcoides species. AB - During microbial reductive dechlorination of tetrachloroethene (PCE) and trichloroethene (TCE), trans-1, 2-dichloroethene (trans-DCE) has been observed to be produced predominantly by certain mixed and pure cultures. However, the reductive dehalogenase (RDase) genes involved in trans-DCE generation remain elusive. In this study, identification and transcriptional analysis of RDases were conducted on trans-DCE-producing Dehalococcoides sp. strain MB. Two pairs of degenerate primers targeting the conserved regions of RDases in known Dehalococcoides species were applied to amplify the putative RDase genes of strain MB. Cloning and restriction analysis revealed the presence of seven unique RDase gene fragments (dceA1 to dceA7) that possess sequence identity to known RDase genes. Gene expression analysis of the PCE-grown culture MB exhibited 10 fold regulation of the RDase gene dceA6 (designated mbrA gene), suggesting that it is involved in the production of trans-DCE. This is in agreement with the molecular size of the most abundant protein that is resolved on the denaturing protein gel. Complete sequence of the mbrA gene was obtained by chromosome walking, and the upstream of it is a regulator of transcription, indicating that the expression of this functional gene is tightly controlled in the microbe. The mbrA gene was subsequently found to be present in other trans-DCE-producing cultures containing Dehalococcoides sp. The new mbrA gene identified in this study may serve as an important biomarker for evaluating, predicting and elucidating the biological production of trans-DCE in the chloroethene contaminated sites. PMID- 20357836 TI - Adaptive hierarchical architecture for visual recognition. AB - We propose a new hierarchical architecture for visual pattern classification. The new architecture consists of a set of fixed, directional filters and a set of adaptive filters arranged in a cascade structure. The fixed filters are used to extract primitive features such as orientations and edges that are present in a wide range of objects, whereas the adaptive filters can be trained to find complex features that are specific to a given object. Both types of filter are based on the biological mechanism of shunting inhibition. The proposed architecture is applied to two problems: pedestrian detection and car detection. Evaluation results on benchmark data sets demonstrate that the proposed architecture outperforms several existing ones. PMID- 20357837 TI - Spatially efficient reference phase-encrypted joint transform correlator. AB - A novel joint transform correlator (JTC) system is presented in which the stored reference image is phase encrypted prior to applying the JTC. The encryption disperses all the trivial correlation peaks in the correlator output. The reference image is encrypted electronically, which simplifies the need for a complex optical setup. The encryption removes the JTC requirement for spatial separation between the reference and the target images in the joint input plane. This efficient use of spatial light modulator space can be used to phase multiplex more reference images so that correlations with multiple reference images can be performed in a single JTC cycle. PMID- 20357838 TI - Spectral fringe-adjusted joint transform correlation. AB - A novel spectral fringe-adjusted joint transform (SFJTC) correlation based technique is proposed for detecting very small targets involving only a few pixels in hyperspectral imagery. In this technique, spectral signatures from the unknown hyperspectral imagery are correlated with the reference signature using the SFJTC technique. This technique can detect both single and/or multiple desired targets in constant time while accommodating the in-plane and out-of plane distortions. Furthermore, in this paper, a new metric, called the peak-to clutter mean, is introduced that provides sharp and high correlation peaks corresponding to targets and makes the proposed technique intensity invariant. Test results using real life hyperspectral image datacubes are presented to verify the effectiveness of the proposed technique. PMID- 20357839 TI - Point spread function engineering for iris recognition system design. AB - Undersampling in the detector array degrades the performance of iris-recognition imaging systems. We find that an undersampling of 8 x 8 reduces the iris recognition performance by nearly a factor of 4 (on CASIA iris database), as measured by the false rejection ratio (FRR) metric. We employ optical point spread function (PSF) engineering via a Zernike phase mask in conjunction with multiple subpixel shifted image measurements (frames) to mitigate the effect of undersampling. A task-specific optimization framework is used to engineer the optical PSF and optimize the postprocessing parameters to minimize the FRR. The optimized Zernike phase enhanced lens (ZPEL) imager design with one frame yields an improvement of nearly 33% relative to a thin observation module by bounded optics (TOMBO) imager with one frame. With four frames the optimized ZPEL imager achieves a FRR equal to that of the conventional imager without undersampling. Further, the ZPEL imager design using 16 frames yields a FRR that is actually 15% lower than that obtained with the conventional imager without undersampling. PMID- 20357840 TI - What can we learn from the shape of a correlation peak for position estimation? AB - Matched filtering is a robust technique to identify and locate objects in the presence of noise. Traditionally, the amplitude of the correlation peak is used for detection of a match. However, when distinguishing objects that are not significantly different or detecting objects under high noise imaging conditions, the normalized peak amplitude alone may not provide sufficient discrimination. In this paper, we demonstrate that measurements derived from the shape of the correlation peak offer not only higher levels of discrimination but also accurate position estimation. To our knowledge, this is the first time such features have been used in a real-time system, like the National Ignition Facility, where such techniques enable real-time, accurate position estimation and alignment under challenging imaging conditions. It is envisioned that systems utilizing matched filtering will greatly benefit from incorporating additional shape based information. PMID- 20357834 TI - Bacterial diversity in rhizosphere soil from Antarctic vascular plants of Admiralty Bay, maritime Antarctica. AB - The Antarctic is a pristine environment that contributes to the maintenance of the global climate equilibrium. The harsh conditions of this habitat are fundamental to selecting those organisms able to survive in such an extreme habitat and able to support the relatively simple ecosystems. The DNA of the microbial community associated with the rhizospheres of Deschampsia antarctica Desv (Poaceae) and Colobanthus quitensis (Kunth) BartI (Caryophyllaceae), the only two native vascular plants that are found in Antarctic ecosystems, was evaluated using a 16S rRNA multiplex 454 pyrosequencing approach. This analysis revealed similar patterns of bacterial diversity between the two plant species from different locations, arguing against the hypothesis that there would be differences between the rhizosphere communities of different plants. Furthermore, the phylum distribution presented a peculiar pattern, with a bacterial community structure different from those reported of many other soils. Firmicutes was the most abundant phylum in almost all the analyzed samples, and there were high levels of anaerobic representatives. Also, some phyla that are dominant in most temperate and tropical soils, such as Acidobacteria, were rarely found in the analyzed samples. Analyzing all the sample libraries together, the predominant genera found were Bifidobacterium (phylum Actinobacteria), Arcobacter (phylum Proteobacteria) and Faecalibacterium (phylum Firmicutes). To the best of our knowledge, this is the first major bacterial sequencing effort of this kind of soil, and it revealed more than expected diversity within these rhizospheres of both maritime Antarctica vascular plants in Admiralty Bay, King George Island, which is part of the South Shetlands archipelago. PMID- 20357841 TI - Experimentally validated computational imaging with adaptive multiaperture folded architecture. AB - We present experimental results of imaging and digital superresolution in a multiaperture miniature folded imaging architecture called PANOPTES. We prove the feasibility of integrating a low f-number folded imagers within a steerable multiaperture framework while maintaining a thin profile. Stringent requirements including low f-number and compact form factor, combined with the need for an ability to steer individual fields of view necessitate an off-axis design, resulting in a plane symmetric optical system. We present a detailed description of the ensuing optical design and its performance. The feasibility of this architecture is demonstrated through experiments and preliminary reconstruction results. PMID- 20357842 TI - Identification of fluorescent beads using a coded aperture snapshot spectral imager. AB - We apply a coded aperture snapshot spectral imager (CASSI) to fluorescence microscopy. CASSI records a two-dimensional (2D) spectrally filtered projection of a three-dimensional (3D) spectral data cube. We minimize a convex quadratic function with total variation (TV) constraints for data cube estimation from the 2D snapshot. We adapt the TV minimization algorithm for direct fluorescent bead identification from CASSI measurements by combining a priori knowledge of the spectra associated with each bead type. Our proposed method creates a 2D bead identity image. Simulated fluorescence CASSI measurements are used to evaluate the behavior of the algorithm. We also record real CASSI measurements of a ten bead type fluorescence scene and create a 2D bead identity map. A baseline image from filtered-array imaging system verifies CASSI's 2D bead identity map. PMID- 20357843 TI - Artificial neural networks using complex numbers and phase encoded weights. AB - The model of a simple perceptron using phase-encoded inputs and complex-valued weights is proposed. The aggregation function, activation function, and learning rule for the proposed neuron are derived and applied to Boolean logic functions and simple computer vision tasks. The complex-valued neuron (CVN) is shown to be superior to traditional perceptrons. An improvement of 135% over the theoretical maximum of 104 linearly separable problems (of three variables) solvable by conventional perceptrons is achieved without additional logic, neuron stages, or higher order terms such as those required in polynomial logic gates. The application of CVN in distortion invariant character recognition and image segmentation is demonstrated. Implementation details are discussed, and the CVN is shown to be very attractive for optical implementation since optical computations are naturally complex. The cost of the CVN is less in all cases than the traditional neuron when implemented optically. Therefore, all the benefits of the CVN can be obtained without additional cost. However, on those implementations dependent on standard serial computers, CVN will be more cost effective only in those applications where its increased power can offset the requirement for additional neurons. PMID- 20357844 TI - Acceleration of spiking neural network based pattern recognition on NVIDIA graphics processors. AB - There is currently a strong push in the research community to develop biological scale implementations of neuron based vision models. Systems at this scale are computationally demanding and generally utilize more accurate neuron models, such as the Izhikevich and the Hodgkin-Huxley models, in favor of the more popular integrate and fire model. We examine the feasibility of using graphics processing units (GPUs) to accelerate a spiking neural network based character recognition network to enable such large scale systems. Two versions of the network utilizing the Izhikevich and Hodgkin-Huxley models are implemented. Three NVIDIA general purpose (GP) GPU platforms are examined, including the GeForce 9800 GX2, the Tesla C1060, and the Tesla S1070. Our results show that the GPGPUs can provide significant speedup over conventional processors. In particular, the fastest GPGPU utilized, the Tesla S1070, provided a speedup of 5.6 and 84.4 over highly optimized implementations on the fastest central processing unit (CPU) tested, a quadcore 2.67 GHz Xeon processor, for the Izhikevich and the Hodgkin-Huxley models, respectively. The CPU implementation utilized all four cores and the vector data parallelism offered by the processor. The results indicate that GPUs are well suited for this application domain. PMID- 20357845 TI - Compressive video sensors using multichannel imagers. AB - We explore the possibilities of obtaining compression in video through modified sampling strategies using multichannel imaging systems. The redundancies in video streams are exploited through compressive sampling schemes to achieve low power and low complexity video sensors. The sampling strategies as well as the associated reconstruction algorithms are discussed. These compressive sampling schemes could be implemented in the focal plane readout hardware resulting in drastic reduction in data bandwidth and computational complexity. PMID- 20357846 TI - Large-scale pose-invariant face recognition using cellular simultaneous recurrent network. AB - In this work, we propose a novel technique for face recognition with +/-90 degrees pose variations in image sequences using a cellular simultaneous recurrent network (CSRN). We formulate the recognition problem with such large pose variations as an implicit temporal prediction task for CSRN. We exploit a face extraction algorithm based on the scale-space method and facial structural knowledge as a preprocessing step. Further, to reduce computational cost, we obtain eigenfaces for a set of image sequences for each person and use these reduced pattern vectors as the input to CSRN. CSRN learns how to associate each face class/person in the training phase. A modified distance metric between successive frames of test and training output pattern vectors indicate either a match or mismatch between the two corresponding face classes. We extensively evaluate our CSRN-based face recognition technique using the publicly available VidTIMIT Audio-Video face dataset. Our simulation shows that for this dataset with large-scale pose variations, we can obtain an overall 77% face recognition rate. PMID- 20357847 TI - Convergence in optical and digital pattern recognition: introduction to the feature issue. AB - This Applied Optics feature issue, in addition to optical and digital pattern recognition, includes their convergence in the form of computational imaging. PMID- 20357849 TI - Nd:glass regenerative amplifier with increased bandwidth and high output energy for chirped pulse amplification systems. AB - We demonstrate a large energy output and a wider output spectral bandwidth from Nd:glass-based regenerative amplifiers. The maximum energy extracted from the regenerative amplifier is 24 mJ with an overall gain of 3.4 x 10(8). The maximum output bandwidth achieved is 4.2 nm FWHM when the input pulse spectral bandwidth is 7 nm FWHM. This was made possible by a new cavity optimization technique. PMID- 20357848 TI - Biophotonic in situ sensor for plant leaves. AB - Knowledge of the water concentration of plants can be helpful in several environmental and agricultural domains. There are many methods for the determination of water content in plant leaves; however, most of them give a relative moisture level or an analytical measure after a previous calibration procedure. Even for other biochemical compounds such as dry matter or chlorophyll, the measurement techniques could be destructive. For this reason, a nondestructive method has been developed to measure the biochemical compounds of a plant leaf, using an infrared spectroscopy technique. One important advantage is the simplicity of the device (RAdiometre portatif de Mesure In Situ, RAMIS) and its capability to perform measurements in situ. The prototype is a leaf-clip configuration and is made of LEDs at five wavelengths (656, 721, 843, 937, and 1550 nm), and a silicon/germanium photosensor. To compute the water content of vegetative leaves, the radiative transfer model PROSPECT was implemented. This model can accurately predict spectral transmittances in the 400 nm to 2500 nm spectral region as a function of the principal leaf biochemical contents: water, dry matter, and chlorophyll. Using the transmittance measured by RAMIS into an inversion procedure of PROSPECT: A Model of Leaf Optical Properties Spectra, we are able to compute the values of water contents that show an agreement with the water contents measured directly using dry weight procedures. This method is presented as a possibility to estimate other leaf biochemical compounds using appropriate wavelengths. PMID- 20357850 TI - Rapid and accurate estimation of blood saturation, melanin content, and epidermis thickness from spectral diffuse reflectance. AB - We present a method to determine chromophore concentrations, blood saturation, and epidermal thickness of human skin from diffuse reflectance spectra. Human skin was approximated as a plane-parallel slab of variable thickness supported by a semi-infinite layer corresponding to the epidermis and dermis, respectively. The absorption coefficient was modeled as a function of melanin content for the epidermis and blood content and oxygen saturation for the dermis. The scattering coefficient and refractive index of each layer were found in the literature. Diffuse reflectance spectra between 490 and 620 nm were generated using Monte Carlo simulations for a wide range of melanosome volume fraction, epidermal thickness, blood volume, and oxygen saturation. Then, an inverse method was developed to retrieve these physiologically meaningful parameters from the simulated diffuse reflectance spectra of skin. A previously developed accurate and efficient semiempirical model for diffuse reflectance of two layered media was used instead of time-consuming Monte Carlo simulations. All parameters could be estimated with relative root-mean-squared error of less than 5% for (i) melanosome volume fraction ranging from 1% to 8%, (ii) epidermal thickness from 20 to 150 mum, (iii) oxygen saturation from 25% to 100%, (iv) blood volume from 1.2% to 10%, and (v) tissue scattering coefficient typical of human skin in the visible part of the spectrum. A similar approach could be extended to other two layer absorbing and scattering systems. PMID- 20357851 TI - Study of azo dye surface command photoalignment material for photonics applications. AB - We provide detailed quantitative characterization of sulfonic bisazodye SD1 as a photoalignment material for photonics applications. The reversibility of photoalignment was tested for transformations between planar and 90 degrees twist orientation states in a liquid crystal (LC) cell using polarized UV light. No degradation was observed for 100 cycles of transformations. A given twist angle of the LC orientation was obtained in a single step, as well as in a sequence of gradually increasing angles. A hysteresis is revealed in the latter case for planar-twist-planar cycles. The material was used for obtaining patterned orientation of a LC polymer providing similarly good quality photoalignment for UV as well as visible light. High efficiency large area and high spatial frequency optical axis gratings (or, polarization gratings) were demonstrated on a polycarbonate substrate. We show the opportunity of obtaining photoalignment in a multilayer system with single exposure to a polarized light. Finally, we provide evidence of a positive feedback in the dynamics of photoalignment due to the orientational effect of an increasing number of aligned molecules. PMID- 20357852 TI - Microwave response of magnetized hydrogen plasma in carbon nanotubes: multiple reflection effects. AB - We derived simple sets of equations to describe the microwave response of the magnetized hydrogen plasma slab embedded inside carbon nanotubes, which were grown by iron-catalyzed high-pressure disproportionation. These equations, which are useful when interference effects due to multiple reflections between plasma film interfaces are small, were used to analyze the reflection, absorption, and transmission coefficients of the magnetized hydrogen plasma slab. A discussion on the effects of the continuously changing external magnetic field and hydrogen plasma parameters on the reflected power, absorbed power, and transmitted power in the system is presented. PMID- 20357853 TI - Grating-based optical scheme for the universal generation of inhomogeneously polarized laser beams. AB - We propose and analyze a new optical system to transform linearly polarized laser modes into axially symmetric (radial or azimuthal) modes that show more promise in various applications, as well as generating various inhomogeneously polarized configurations. The system is based on the coherent composition of modal beams with phase diffraction gratings that allow the intermode phase shift to be varied without the need for auxiliary components. What makes the system simple and universal is the use of diffractive optical elements to generate required mode patterns with specific space orientation along with the simultaneous generation of different beams with different transverse mode content, all of which can subsequently be combined. PMID- 20357854 TI - Deep-etched sinusoidal polarizing beam splitter grating. AB - A sinusoidal-shaped fused-silica grating as a highly efficient polarizing beam splitter (PBS) is investigated based on the simplified modal method. The grating structure depends mainly on the ratio of groove depth to grating period and the ratio of incident wavelength to grating period. These ratios can be used as a guideline for the grating design at different wavelengths. A sinusoidal-groove PBS grating is designed at a wavelength of 1310 nm under Littrow mounting, and the transmitted TM and TE polarized waves are mainly diffracted into the zeroth order and the -1st order, respectively. The grating profile is optimized by using rigorous coupled-wave analysis. The designed PBS grating is highly efficient (>95.98%) over the O-band wavelength range (1260-1360 nm) for both TE and TM polarizations. The sinusoidal grating can exhibit higher diffraction efficiency, larger extinction ratio, and less reflection loss than the rectangular-groove PBS grating. By applying wet etching technology on the rectangular grating, which was manufactured by holographic recording and inductively coupled plasma etching technology, the sinusoidal grating can be approximately fabricated. Experimental results are in agreement with theoretical values. PMID- 20357855 TI - Temperature performance of a macrobending single-mode fiber-based refractometer. AB - We present, theoretically and experimentally, an investigation of temperature dependence of a macrobending single-mode fiber-based refractometer utilizing a ratiometric scheme. The conventional scalar approximation method is utilized for predicting the temperature dependent loss of the proposed fiber refractometer. An all-fiber ratiometric measurement system is built to allow the comparison of modeled and measured results. Calculated and measured results for an SMF28 refractometer are in good agreement and confirm the effect of temperature on refractive index measurements. Both calculated and measured ratio responses monotonically change with temperature, which allows for a temperature correction process. PMID- 20357856 TI - Rough Fresnel zone plates over metallic surfaces. AB - We analyze the focusing properties of Fresnel zone plates fabricated over steel tapes using laser ablation. Our intention is to implement the use of micro optical elements when the use of conventional chrome-glass elements is not indicated. Because of the manufacture process, the surface presents a certain anisotropic roughness, which reduces the focusing properties. First, we develop numerical simulations by means of the Rayleigh-Sommerfeld approach, showing how roughness in both levels of the Fresnel zone plate affects the focalization of the lens. We also manufacture Fresnel zone plates over steel tape, and perform experimental verification that corroborates the numerical results. PMID- 20357857 TI - Highly efficient refractive Gaussian-to-tophat beam shaper for compact terahertz imager. AB - We describe an efficient and compact terahertz (THz) illumination system as part of an active THz imager. The design and fabrication methods are verified by comparing measurements with wave optical simulations that form a basis for the design of a Gaussian-to-tophat beam shaper. Introducing realistic alignment tolerances in the simulations led to an improved agreement with the experimental data. Furthermore, we propose a method to reduce the alignment effort for THz beam shaping elements by correlating measured results with simulated data of a misaligned system. PMID- 20357858 TI - Correction method for stripe nonuniformity. AB - Stripe nonuniformity is very typical in line infrared focal plane arrays (IR-FPA) and uncooled staring IR-FPA. In this paper, the mechanism of the stripe nonuniformity is analyzed, and the gray-scale co-occurrence matrix theory and optimization theory are studied. Through these efforts, the stripe nonuniformity correction problem is translated into the optimization problem. The goal of the optimization is to find the minimal energy of the image's line gradient. After solving the constrained nonlinear optimization equation, the parameters of the stripe nonuniformity correction are obtained and the stripe nonuniformity correction is achieved. The experiments indicate that this algorithm is effective and efficient. PMID- 20357859 TI - Further investigation of the characteristics of nodular defects. AB - To increase the understanding of the damage sensitivity of nodular defects and provide exact evidence for theoretical study, the structures and the damage behavior of nodular defects in electron-beam deposited mirrors of HfO(2)/SiO(2) are systemically investigated with a double-beam microscope (focused ion beam, scanning electron microscope). Nodular defects are classified into two kinds. In one kind the boundaries between nodules and the surrounding layers have become continuous for the last deposited materials, and in the other there are discontinuous boundaries between nodules and the surrounding layers. Nodular defects of the first kind typically have low domes, and the second have high domes. Laser damage experiments show that nodular defects of the first kind usually have a high laser resistance, and the laser-induced damage thresholds are limited in the second class of nodules. The dominant parameter of nodular defects related to damage is the height of the nodular defect. PMID- 20357860 TI - Clustering-based robust three-dimensional phase unwrapping algorithm. AB - Relatively recent techniques that produce phase volumes have motivated the study of three-dimensional (3D) unwrapping algorithms that inherently incorporate the third dimension into the process. We propose a novel 3D unwrapping algorithm that can be considered to be a generalization of the minimum spanning tree (MST) approach. The technique combines characteristics of some of the most robust existing methods: it uses a quality map to guide the unwrapping process, a region growing mechanism to progressively unwrap the signal, and also cut surfaces to avoid error propagation. The approach has been evaluated in the context of noncontact measurement of dynamic objects, suggesting a better performance than MST-based approaches. PMID- 20357861 TI - Three-dimensional measurement of small mechanical parts under a complicated background based on stereo vision. AB - We present an effective method for the accurate three-dimensional (3D) measurement of small industrial parts under a complicated noisy background, based on stereo vision. To effectively extract the nonlinear features of desired curves of the measured parts in the images, a strategy from coarse to fine extraction is employed, based on a virtual motion control system. By using the multiscale decomposition of gray images and virtual beam chains, the nonlinear features can be accurately extracted. By analyzing the generation of geometric errors, the refined feature points of the desired curves are extracted. Then the 3D structure of the measured parts can be accurately reconstructed and measured with least squares errors. Experimental results show that the presented method can accurately measure industrial parts that are represented by various line segments and curves. PMID- 20357862 TI - Numerical simulation of dual-loss-modulated Q-switched and mode-locked laser with an acousto-optic and Cr4+:YAG saturable absorber. AB - By considering the influence of the turn-off time and the modulation frequency of the acousto-optic (AO) modulator as well as the Gaussian spatial distribution of the photon density, we give a developed rate equation model for a diode-pumped dual-loss-modulated Q-switched and mode-locked (QML) Nd:GdVO(4) laser with AO modulator and Cr(4+):YAG saturable absorber. With this developed model, the dual loss-modulated QML laser characteristics, such as pulse width and pulse energy, can be numerically simulated, and the theoretical evaluations are in good agreement with the experimental results. PMID- 20357863 TI - Coherent 2 microm differential absorption and wind lidar with conductively cooled laser and two-axis scanning device. AB - A coherent 2 microm differential absorption and wind lidar (Co2DiaWiL) was developed to measure CO(2) concentration and line-of-sight wind speed. We conductively cooled a pumping laser head to -80 degrees C and diode arrays to approximately 20 degrees C. A Q-switched laser outputs an energy of 80 mJ (pulse width 150 ns (FWHM), pulse repetition frequency up to 30 Hz). CO(2) measurements made over a column range (487-1986 m) for 5 min accumulation time pairs achieved 0.7% precision. Line-of-sight wind speeds for ranges up to approximately 20 km and returns from a mountainside located 24 km away from the Co2DiaWiL were obtained. PMID- 20357864 TI - Optical transfer functions derived from solar adaptive optics system data. AB - Adaptive optics (AO) systems installed at large ground-based telescopes partially correct Earth's atmosphere, making post facto image reconstruction techniques necessary to produce diffraction-limited observations. To achieve accurate photometry in the reconstructed images, some post facto techniques require knowledge of transfer functions that describe the optical system. I present a new, fast method for the estimation of the long-exposure and speckle transfer functions from data gathered by a solar AO system simultaneously with the observations. The results of the presented method are tested with extensive analytical models, demonstrating that the estimation is robust for situations where the AO system is performing with Strehl ratios larger than 45%. Application to observations of solar granulation produces reconstructed images that are photometrically in agreement with earlier results. PMID- 20357865 TI - Phase retrieval by means of a spatial light modulator in the Fourier domain of an imaging system. AB - We present an experimental configuration for phase retrieval from a set of intensity measurements. The key component is a spatial light modulator located in the Fourier domain of an imaging system. It performs a linear filter operation that is associated to the process of propagation in the image plane. In contrast to the state of the art, no mechanical adjustment is required during the recording process, thus reducing the measurement time considerably. The method is experimentally demonstrated by investigating a wave field scattered by a diffuser, and the results are verified by comparing them to those obtained from standard interferometry. PMID- 20357866 TI - Phase and amplitude retrieval of objects embedded in a sinusoidal background from its diffraction pattern. AB - Efforts of phase and amplitude retrieval from diffraction patterns have almost exclusively been applied for nonperiodic objects. We investigated the quality of retrieval of nonperiodic objects embedded in a sinusoidal background, using the approach of iterative hybrid input-output with oversampling. Two strategies were employed; one by filtering in the frequency domain prior to phase retrieval, and the other by filtering the phase or amplitude image after retrieval. Results obtained indicate better outcomes with the latter approach provided detector noise is not excessive. PMID- 20357867 TI - Experimental generation of Laguerre-Gaussian beam using digital micromirror device. AB - A digital micromirror device (DMD) modulates laser intensity through computer control of the device. We experimentally investigate the performance of the modulation property of a DMD and optimize the modulation procedure through image correction. Furthermore, Laguerre-Gaussian (LG) beams with different topological charges are generated by projecting a series of forklike gratings onto the DMD. We measure the field distribution with and without correction, the energy of LG beams with different topological charges, and the polarization property in sequence. Experimental results demonstrate that it is possible to generate LG beams with a DMD that allows the use of a high-intensity laser with proper correction to the input images, and that the polarization state of the LG beam differs from that of the input beam. PMID- 20357868 TI - Tip-enhanced Raman spectroscopy with silver-coated optical fiber probe in reflection mode for investigating multiwall carbon nanotubes. AB - We developed a tip-enhanced Raman spectrometer (TERS) with reflection mode. The instrument, with a scanning shear-force microscope (ShFM) and a side-illumination Raman spectroscope, can overcome the diffraction limit and has high sensitivity. A chemical method to fabricate optical fiber probes with Ag coating is proposed. The local electromagnetic responses of the silver-coated optical fiber probe are numerically analyzed by the finite-difference time-domain method, and the excitation wavelength is optimized to resonate with the localized surface plasmons (LSP) of the probe tip. The instrument is applied to investigate a single multiwall carbon nanotube. The experiment results indicate that our TERS instrument has a spatial resolution better than 70 nm, and the enhancement factor is about 5 x 10(3). PMID- 20357869 TI - Deformation-free form error measurement of thin, plane-parallel optics floated on a heavy liquid. AB - We describe a novel method for measuring the unconstrained flatness error of thin, plane-parallel precision optics. Test parts are floated on high-density aqueous metatungstate solutions while measuring the flatness error with an interferometer. The support of the flat optics by the uniform hydrostatic pressure at the submerged face of the flat optic eliminates flatness errors caused by mounting forces. A small, well characterized flatness error results from the bending of the floating flat by the hydrostatic pressure gradient at the edges. An equation describing the bending of thin, flat plates floating on a liquid is derived, which can be used to correct the flatness measurements of arbitrarily shaped plates. The method can be used to measure flatness errors of both nontransparent and transparent parts, and it is illustrated with flatness measurements of photomask blanks and substrates for extreme ultraviolet lithography. The refractive index of a saturated aqueous lithium metatungstate solution was measured at 632.8 nm and was found to be close to the refractive indices of several low thermal expansion optical materials. PMID- 20357870 TI - Internal quantum efficiency modeling of silicon photodiodes. AB - Results are presented for modeling of the shape of the internal quantum efficiency (IQE) versus wavelength for silicon photodiodes in the 400 nm to 900 nm wavelength range. The IQE data are based on measurements of the external quantum efficiencies of three transmission optical trap detectors using an extensive set of laser wavelengths, along with the transmittance of the traps. We find that a simplified version of a previously reported IQE model fits the data with an accuracy of better than 0.01%. These results provide an important validation of the National Institute of Standards and Technology (NIST) spectral radiant power responsivity scale disseminated through the NIST Spectral Comparator Facility, as well as those scales disseminated by other National Metrology Institutes who have employed the same model. PMID- 20357871 TI - Optical monitoring of anchoring change in vertically aligned thin liquid crystal film for chemical and biological sensor. AB - A significant advance in sensitivity of liquid-crystal (LC)-based chemical and biological sensors can be achieved by actively monitoring anchoring energy change. We simulate the deformation of a LC director with different anchoring energies using the finite element method and the optical properties of the LC film using the finite-difference time-domain method. Polarizing micrographs are collected and compared with simulated textures. Measurement of optical transmission is used to monitor the anchoring change. Experimental and simulation results both demonstrate the optical method can effectively monitor the surface anchoring change due to the presence of targeted analytes. PMID- 20357872 TI - Spectral characterization of a photonic bandgap fiber for sensing applications. AB - We study the measurand-induced spectral shift of the photonic bandgap edge of a hollow-core photonic crystal fiber. The physical measurands considered are strain, temperature, curvature, and twist. A noticeable sensitivity to strain, temperature, and twist is observed, with a blueshift to increase strain and twist. An increase in temperature induces a redshift. On the other hand, curvature has no observable effect on the spectral position of the photonic bandgap edge. PMID- 20357873 TI - Ion-implanted polymethyl methacrylate beam splitter/coupler for 1.55 microm applications. AB - The applicability of layers of ion-implanted polymethyl methacrylate (PMMA) for beam splitting of laser light at the telecommunications wavelength of 1.55 mum is examined. Bulk PMMA is studied, subjected to low-energy (50 keV) silicon ion implantation at various ion fluences in the range from 10(14) to 10(17) cm(-2). The formed ultrathin near-surface ion-implanted layer of a thickness of about 100 nm, buried in a depth of approximately 100 nm, can be used to split (or combine) laser beams at 1.55 microm with a low absorption loss. PMID- 20357874 TI - Narrow-bandwidth tunable picosecond pulses in the visible produced by noncollinear optical parametric amplification with a chirped blue pump. AB - Narrow-bandwidth (approximately 27 cm(-1)) tunable picosecond pulses from 480 nm 780 nm were generated from the output of a 1 kHz femtosecond titanium:sapphire laser system using a type I noncollinear optical parametric amplifier (NOPA) with chirped second-harmonic generation (SHG) pumping. Unlike a femtosecond NOPA, this system utilizes a broadband pump beam, the chirped 400 nm SHG of the Ti:sapphire fundamental, to amplify a monochromatic signal beam (spectrally-filtered output of a type II collinear OPA). Optimum geometric conditions for simultaneous phase- and group-velocity matching were calculated in the visible spectrum. This design is an efficient and simple method for generating tunable visible picosecond pulses that are synchronized to the femtosecond pulses. PMID- 20357875 TI - Development of image mappers for hyperspectral biomedical imaging applications. AB - A new design and fabrication method is presented for creating large-format (>100 mirror facets) image mappers for a snapshot hyperspectral biomedical imaging system called an image mapping spectrometer (IMS). To verify this approach a 250 facet image mapper with 25 multiple-tilt angles is designed for a compact IMS that groups the 25 subpupils in a 5 x 5 matrix residing within a single collecting objective's pupil. The image mapper is fabricated by precision diamond raster fly cutting using surface-shaped tools. The individual mirror facets have minimal edge eating, tilt errors of <1 mrad, and an average roughness of 5.4 nm. PMID- 20357876 TI - Low-loss ultracompact optical power splitter using a multistep structure. AB - We propose a low-loss ultracompact optical power splitter for broadband passive optical network applications. The design is based on a multistep structure involving a two-material (core/cladding) system. The performance of the proposed device was evaluated through the three-dimensional finite-difference beam propagation method. By using the proposed design, an excess loss of 0.4 dB was achieved at a full branching angle of 24 degrees. The wavelength-dependent loss was found to be less than 0.3 dB, and the polarization-dependent loss was less than 0.05 dB from O to L bands. The device offers the potential of being mass produced using low-cost polymer-based embossing techniques. PMID- 20357877 TI - Periodic, pseudonoise waveforms for multifunction coherent ladar. AB - We report the use of periodic, pseudonoise waveforms in a multifunction coherent ladar system. We exploit the Doppler sensitivity of these waveforms, as well as agile processing, to enable diverse ladar functions, including high range resolution imaging, macro-Doppler imaging, synthetic aperture ladar, and range resolved micro-Doppler imaging. We present analytic expressions and simulations demonstrating the utility of pseudonoise waveforms for each of the ladar modes. We also discuss a laboratory pseudonoise ladar system that was developed to demonstrate range compression and range-resolved micro-Doppler imaging, as well as the phase recovery common to each of the coherent modes. PMID- 20357878 TI - Channel model for InSb-based superresolution optical disc system. AB - A signal model of a superresolution optical channel would be an efficient tool for developing components of an associated high-density optical disc system. While the behavior of the laser diode, aperture, lens, and detector is properly described, a general mathematical model of the superresolution disc itself is not yet available. However, different approaches have been made to describe the properties of a mask layer, mainly based on temperature- or power-dependent nonlinear effects. The main problem of the modeling is that temperature-dependent material properties, such as thermal conductivity and refractive indices, are not known or not accurate enough to allow quantitative predictions. Therefore, it could be useful to define a signal-based or phenomenological model that can be calibrated with experimental data. In this contribution, we developed a complete optical channel model--from non-return-to-zero inverted (NRZI) input to disc readout signal--including the reflectivity of a superresolution disc with InSb used for the mask layer. Model parameters are derived from data measured using a static tester. The model is finally applied to a configuration appropriate for a dynamic superresolution optical drive by moving the focused spot relative to the material. PMID- 20357880 TI - Inscription and characterization of waveguides written into borosilicate glass by a high-repetition-rate femtosecond laser at 800 nm. AB - A series of waveguides was inscribed in a borosilicate glass (BK7) by an 11 MHz repetition rate femtosecond laser operating with pulse energies from 16 to 30 nJ and focused at various depths within the bulk material. The index modification was measured using a quantitative phase microscopy technique that revealed central index changes ranging from 5 x 10(-3) to 10(-2), leading to waveguides that exhibited propagation losses of 0.2 dB/cm at a wavelength of 633 nm and 0.6 dB/cm at a wavelength of 1550 nm with efficient mode matching, less than 0.2 dB, to standard optical fibers. Analysis of the experimental data shows that, for a given inscription energy, the index modification has a strong dependence on inscription scanning velocity. At higher energies, the index modification increases with increasing inscription scanning velocity with other fabrication parameters constant. PMID- 20357879 TI - Multiple source frequency-modulated continuous-wave optical reflectometry: theory and experiment. AB - We propose and demonstrate a novel approach to increase the effective bandwidth of a frequency-modulated continuous-wave (FMCW) ranging system. This is achieved by algorithmically stitching together the swept spectra of separate laser sources. The result is an improvement in the range resolution proportional to the increase in the swept-frequency range. An analysis of this system as well as the outline of the stitching algorithm are presented. Using three distinct swept frequency optical waveforms, we experimentally demonstrate a threefold improvement in the range resolution of a three-sweep approach over the conventional FMCW method. PMID- 20357881 TI - Process parameter effects on material removal in magnetorheological finishing of borosilicate glass. AB - We investigate the effects of processing parameters on material removal for borosilicate glass. Data are collected on a magnetorheological finishing (MRF) spot taking machine (STM) with a standard aqueous magnetorheological (MR) fluid. Normal and shear forces are measured simultaneously, in situ, with a dynamic dual load cell. Shear stress is found to be independent of nanodiamond concentration, penetration depth, magnetic field strength, and the relative velocity between the part and the rotating MR fluid ribbon. Shear stress, determined primarily by the material mechanical properties, dominates removal in MRF. The addition of nanodiamond abrasives greatly enhances the material removal efficiency, with the removal rate saturating at a high abrasive concentration. The volumetric removal rate (VRR) increases with penetration depth but is insensitive to magnetic field strength. The VRR is strongly correlated with the relative velocity between the ribbon and the part, as expected by the Preston equation. A modified removal rate model for MRF offers a better estimation of MRF removal capability by including nanodiamond concentration and penetration depth. PMID- 20357882 TI - Generalized method for calculating astigmatism of the unit-magnification multipass system. AB - A generalized method to accurately calculate astigmatism of the unit magnification multipass system (UMS) is proposed. A practical coaxial optical transmission model is developed for the UMS. Astigmatism analysis is then made convenient by a 4 by 4 general transfer matrix. Astigmatism correction is significantly promoted, and hence further improvement in imaging quality can be expected. Good agreement between numerical simulations and Zemax ray tracing results verifies the effectiveness of this method. The resulted RMS spot size of this method is only 25% to 64% of other previous methods based on the golden section search for minimum astigmatism in real design cases. This method is helpful for the optical design of the UMS. PMID- 20357883 TI - Efficient coupling of narrow beams into polyimide waveguides by means of grating couplers with high-index coating. AB - The effect of a thin high-index coating deposited on polyimide waveguide grating couplers was investigated. A comprehensive numerical study was performed using an efficient simulation tool based on a Floquet-Bloch algorithm, and the results of this study were compared with experimentally obtained values for input coupling efficiencies. The application of a high-index coating permits efficient coupling from narrow beams even in material systems with a low index difference. This not only facilitates a denser integration of grating couplers but also permits low loss lateral tapering to single-mode waveguides. PMID- 20357884 TI - Relaxation oscillation in Er3+-doped and Yb3+/Er3+ co-doped fiber grating lasers. AB - Relaxation oscillations in Er(3+)-doped and Yb(3+)/Er(3+) co-doped fiber grating lasers were investigated. Intensity noise models were established for both cases in which the fluctuations of pump power and cavity loss were analyzed. Simulation indicates that the relaxation oscillation is induced by the pump power fluctuation, and fluctuation of the cavity loss can broaden the relaxation oscillation peak and enhance the amplitude. The relaxation oscillation of a laser with Er(3+)-doped fiber exhibits a lower frequency and larger amplitude than that of an Yb(3+)/Er(3+) co-doped fiber grating laser. Distributed Bragg reflector fiber grating lasers with Er(3+)-doped fiber and Yb(3+)/Er(3+) co-doped fiber were fabricated, and the relaxation oscillations were measured. For the former, the relaxation oscillation frequency is at the magnitude of several hundreds of kilohertz and linearly shifts toward the higher frequency with the pump power. For the latter, no obvious relaxation oscillation was measured. PMID- 20357886 TI - Optical rotor capable of controlling clockwise and counterclockwise rotation in optical tweezers by displacing the trapping position. AB - A clockwise rotor and a counterclockwise rotor (a clockwise rotor placed upside down) are linked on the optical axis to control the rotation direction in optical tweezers by displacing the trapping (focus) position. The dependence of optical torque on the trapping position of this linked rotor is analyzed using an upward directed focused beam as illumination, via an objective lens with a numerical aperture of 1.4, using a ray optics model under the condition that laser light is incident to not only the lower surfaces, but also to the side surfaces of both rotors. The rotation rate in water is also simulated for an SU-8 linked rotor with 20 microm diameter at a laser power of 200 mW, with rotor thickness as a parameter, by balancing the optical torque with the drag force evaluated using computational fluid dynamics. It is confirmed that the rotation direction changes from clockwise to counterclockwise with the displacement of the trapping position, that almost the same rotation speed is possible in both directions, and that both speeds increase, reach a maximum at a rotor thickness of 9 microm, and then decrease as the thickness increases. PMID- 20357885 TI - Ultrawideband photonic crystal fiber coupler for multiband optical imaging system. AB - We report a photonic crystal fiber (PCF) coupler having an ultrawide spectral bandwidth keeping single mode operation. The use of the PCF coupler in a fiber based optical coherence tomography (OCT) system enables us to handle the wide spectral bands of various light sources, including superluminescent diodes (SLDs) at 1300 nm and 820 nm, Ti:sapphire lasers, and white-light sources. The multiband imaging performances of the PCF-based OCT system are demonstrated by obtaining dental images at 1300 nm and 820 nm with the same setup. In addition, we show that the PCF coupler could cover the spectrum over a one octave span and guide both the fundamental wave (1030 nm) and the second harmonic wave (515 nm) simultaneously. PMID- 20357888 TI - Information: currency of life? AB - In biology, the exception is mostly the rule, and the rule is mostly the exception. However, recent results indicate that known universal concepts in biology such as the genetic code or the utilization of ATP as a source of energy may be complemented by a large class of principles based on Shannon's concept of information. The present position paper discusses various promising pathways toward the formulation of such generic informational principles and their relevance for the realm of biology. PMID- 20357889 TI - Stigmergic gene transfer and emergence of universal coding. AB - We consider a simple information-theoretic model for evolutionary dynamics approaching the "coding threshold," where the capacity to symbolically represent nucleic acid sequences emerges in response to a change in environmental conditions. We study the conditions when a coupling between the dynamics of a "proto-cell" and its proto-symbolic representation becomes beneficial in terms of preserving the proto-cell's information in a noisy environment. In particular, we are interested in understanding the behavior at the "error threshold" level, which, in our case, turns out to be a whole "error interval." The useful coupling is accompanied by self-organization of internal processing, i.e., an increase in complexity within the evolving system. Second, we study whether and how different proto-cells can stigmergically share such information via a joint encoding, even if they have slightly different individual dynamics. Implications for the emergence of biological genetic code are discussed. PMID- 20357890 TI - How evolution guides complexity. AB - Long-standing debates about the role of natural selection in the growth of biological complexity over geological time scales are difficult to resolve from the paleobiological record. Using an evolutionary model-a computational ecosystem subjected to natural selection-we investigate evolutionary trends in an information-theoretic measure of the complexity of the neural dynamics of artificial agents inhabiting the model. Our results suggest that evolution always guides complexity change, just not in a single direction. We also demonstrate that neural complexity correlates well with behavioral adaptation but only when complexity increases are achieved through natural selection (as opposed to increases generated randomly or optimized via a genetic algorithm). We conclude with a suggested research direction that might be able to use the artificial neural data generated in these experiments to determine which aspects of network structure give rise to evolutionarily meaningful neural complexity. PMID- 20357887 TI - From evidence to inference: probing the evolution of protein interaction networks. AB - The evolutionary mechanisms by which protein interaction networks grow and change are beginning to be appreciated as a major factor shaping their present-day structures and properties. Starting with a consideration of the biases and errors inherent in our current views of these networks, we discuss the dangers of constructing evolutionary arguments from naive analyses of network topology. We argue that progress in understanding the processes of network evolution is only possible when hypotheses are formulated as plausible evolutionary models and compared against the observed data within the framework of probabilistic modeling. The value of such models is expected to be greatly enhanced as they incorporate more of the details of the biophysical properties of interacting proteins, gene phylogeny, and measurement error and as more advanced methodologies emerge for model comparison and the inference of ancestral network states. PMID- 20357891 TI - Initialization and self-organized optimization of recurrent neural network connectivity. AB - Reservoir computing (RC) is a recent paradigm in the field of recurrent neural networks. Networks in RC have a sparsely and randomly connected fixed hidden layer, and only output connections are trained. RC networks have recently received increased attention as a mathematical model for generic neural microcircuits to investigate and explain computations in neocortical columns. Applied to specific tasks, their fixed random connectivity, however, leads to significant variation in performance. Few problem-specific optimization procedures are known, which would be important for engineering applications, but also in order to understand how networks in biology are shaped to be optimally adapted to requirements of their environment. We study a general network initialization method using permutation matrices and derive a new unsupervised learning rule based on intrinsic plasticity (IP). The IP-based learning uses only local learning, and its aim is to improve network performance in a self-organized way. Using three different benchmarks, we show that networks with permutation matrices for the reservoir connectivity have much more persistent memory than the other methods but are also able to perform highly nonlinear mappings. We also show that IP-based on sigmoid transfer functions is limited concerning the output distributions that can be achieved. PMID- 20357892 TI - Integrating ELF4 into the circadian system through combined structural and functional studies. AB - The circadian clock is a timekeeping mechanism that enables anticipation of daily environmental changes. In the plant Arabidopsis thaliana, the circadian system is a multiloop series of interlocked transcription-translation feedbacks. Several genes have been arranged in these oscillation loops, but the position of the core clock gene ELF4 in this network was previously undetermined. ELF4 lacks sequence similarity to known domains, and functional homologs have not yet been identified. Here we show that ELF4 is functionally conserved within a subclade of related sequences, and forms an alpha-helical homodimer with a likely electrostatic interface that could be structurally modeled. We support this hypothesis by expression analysis of new elf4 hypomorphic alleles. These weak mutants were found to have expression level phenotypes of both morning and evening clock genes, implicating multiple entry points of ELF4 within the multiloop network. This could be mathematically modeled. Furthermore, morning expression defects were particular to some elf4 alleles, suggesting predominant ELF4 action just preceding dawn. We provide a new hypothesis about ELF4 in the oscillator-it acts as a homodimer to integrate two arms of the circadian clock. PMID- 20357893 TI - Carbon Dots as Nontoxic and High-Performance Fluorescence Imaging Agents. AB - Fluorescent carbon dots (small carbon nanoparticles with the surface passivated by oligomeric PEG molecules) were evaluated for their cytotoxicity and in vivo toxicity and also for their optical imaging performance in reference to that of the commercially supplied CdSe/ZnS quantum dots. The results suggested that the carbon dots were biocompatible, and their performance as fluorescence imaging agents was competitive. The implication to the use of carbon dots for in vitro and in vivo applications is discussed. PMID- 20357894 TI - Hybrid Vigour? Genes, Genomics, and History. AB - Is the gene 'special' for historians? What effects, if any, has the notion of the 'gene' had on our understanding of history? Certainly, there is a widespread public and professional perception that genetics and history are or should be in dialogue with each other in some way. But historians and geneticists view history and genetics very differently - and assume very different relationships between them. And public perceptions of genes, genetics, genomics, and indeed the nature and meanings of 'history' differ yet again. Here, in looking at the meaning, and the implications - the significance - of the gene (and its corollary scientific disciplines and approaches) specifically to historians, I will focus on two aspects of the discourse. First, I will examine the ways in which historians have thus far approached genes and genetics, and the impact such studies have had on the field. There is considerable overlap between the subject matter of genetics/genomics and many of the most widely used analytic categories of contemporary historiography - race, gender, sexuality, ethnicity, (dis)ability, among others. Yet the impact of genetics and genomics on society has been studied principally by anthropologists, sociologists and ethicists.2 Only two historical sub-disciplines have engaged with the rise of genetics to any significant degree: the histories of science and of medicine. What does this indicate or suggest? Second, I will explore the impact of the 'gene' and genetic understandings (of, for example, the body, health, disease, identity, the family, and evolution) on public conceptions of history itself. PMID- 20357895 TI - TARGETED REJECTION PREDICTS HASTENED ONSET OF MAJOR DEPRESSION. AB - Although severe life stress frequently precipitates the onset of major depression, little is known about the basic nature of stressors in this general category of adversity and how exposure to different life events might be related to clinical aspects of the disorder. We addressed this issue by introducing, and examining the effects of, targeted rejection (TR), which involves the exclusive, active, and intentional social rejection of an individual by others. Twenty-seven adults with major depressive disorder were administered an interview-based measure of life stress. Severe life events that occurred prior to the onset of depression were subsequently coded as TR or as non-TR. Participants who experienced a pre-onset severe TR event became depressed approximately three times faster than did their non-TR counterparts. These findings highlight the potential importance of TR as a marker of hastened depression onset and demonstrate how refining characterizations of stress may advance our understanding of depression. PMID- 20357896 TI - Child Support, Father-Child Contact, and Preteens' Involvement with Nonresidential Fathers: Racial/Ethnic Differences. AB - This study examined how child support, frequency of contact with children, and the relationship between nonresidential parents influenced preteens' reports of the involvement of fathers and mothers in their life. Data are from the National Longitudinal Survey of Youth 1979 (NLSY79) that has followed the children of NLSY mothers from birth into their twenties. Results showed that increases in child support and in contact with the child over time after separation are linked to a better coparental relationship when children are age 11 or 12. This better relationship between parents is, in turn, associated with greater involvement of both mothers and nonresidential fathers with their children. PMID- 20357897 TI - Reporting on first sexual experience: The importance of interviewer-respondent interaction. AB - Survey methodologists typically seek to improve data on sensitive topics by standardizing surveys and avoiding the use of human interviewers. This study uses data collected from 90 never-married young adults in rural Malawi to compare reports on first sexual encounters between a standard survey and an in-depth interview. A significant fraction of young women who claimed in the survey to have never been sexually active affirmed sexual experience during the in-depth interview, fielded shortly thereafter. Two elements of the in-depth interview, flexibility and reciprocal exchange, foster trust and more truthful reporting. The findings contradict the long-standing presumption that face-to-face interviews are inherently threatening when the topic is sex. PMID- 20357898 TI - Environmental exposures to Florida red tides: Effects on emergency room respiratory diagnoses admissions. AB - Human exposure to Florida red tides formed by Karenia brevis, occurs from eating contaminated shellfish and inhaling aerosolized brevetoxins. Recent studies have documented acute symptom changes and pulmonary function responses after inhalation of the toxic aerosols, particularly among asthmatics. These findings suggest that there are increases in medical care facility visits for respiratory complaints and for exacerbations of underlying respiratory diseases associated with the occurrence of Florida red tides.This study examined whether the presence of a Florida red tide affected the rates of admission with a respiratory diagnosis to a hospital emergency room in Sarasota, FL. The rate of respiratory diagnoses admissions were compared for a 3-month time period when there was an onshore red tide in 2001 (red tide period) and during the same 3-month period in 2002 when no red tide bloom occurred (non-red tide period). There was no significant increase in the total number of respiratory admissions between the two time periods. However, there was a 19% increase in the rate of pneumonia cases diagnosed during the red tide period compared with the non-red tide period. We categorized home residence zip codes as coastal (within 1.6 km from the shore) or inland (>1.6 km from shore). Compared with the non-red tide period, the coastal residents had a significantly higher (54%) rate of respiratory diagnoses admissions than during the red tide period. We then divided the diagnoses into subcategories (i.e. pneumonia, bronchitis, asthma, and upper airway disease). When compared with the non-red tide period, the coastal zip codes had increases in the rates of admission of each of the subcategories during the red tide period (i.e. 31, 56, 44, and 64%, respectively). This increase was not observed seen in the inland zip codes.These results suggest that the healthcare community has a significant burden from patients, particularly those who live along the coast, needing emergency medical care for both acute and potentially chronic respiratory illnesses during red tide blooms. PMID- 20357899 TI - Recent advances in polyubiquitin chain recognition. AB - Polyubiquitin chains are regulatory signals for a wide array of biological processes. Recent structural studies reveal novel modes of polyubiquitin chain recognition and implicate the diverse repertoire of interactions in providing the specificity of polyubiquitin recognition. PMID- 20357900 TI - Parent Involvement in School Conceptualizing Multiple Dimensions and Their Relations with Family and Demographic Risk Factors. AB - Parent involvement (PI) in school is associated with more positive academic performance and social competence in children. However, there are inadequacies in current measures of PI and a need for a better understanding of predictors of PI. In this study, measures were obtained from a normative sample of 387 children in kindergarten and first grade from high-risk neighborhoods in 4 different sites. First, a confirmatory factor analysis of a theoretical factor model of PI identified 6 reliable multiple-reporter PI factors: Parent-Teacher Contact, Parent Involvement at School, Quality of Parent-Teacher Relationship, Teacher's Perception of the Parent, Parent Involvement at Home, and Parent Endorsement of School. Next, the relations among 3 specific family and demographic risk factors parental education level, maternal depression, and single-parent status-and these 6 PI factors were examined using path analyses in structural equation modeling. Results indicated that the 3 risk factors were differentially associated with the 6 PI factors: Parental education was significantly associated with 4 PI outcomes, maternal depression was significantly associated with 5 PI outcomes, and single parent status was significantly associated with 3 PI outcomes. No significant ethnic group differences between African American and Caucasian families were found in these relations. PMID- 20357901 TI - Mediating Mechanisms for the Intergenerational Transmission of Constructive Parenting: A Prospective Longitudinal Study. AB - Based on a prospective longitudinal panel data set that was collected at three developmental stages-early adolescence, young adulthood, and middle adulthood- this study investigates marital satisfaction and educational attainment as mediating mechanisms as well as gender's moderating effect for the intergenerational transmission of constructive parenting (N = 1,560). The results show that perceived satisfying experiences with parents during early adolescence are positively related to marital satisfaction and educational attainment in young adulthood, which, in turn, are positively related to individuals' utilization of constructive parenting in middle adulthood. The two mediating mechanisms account for most of the direct effect of the intergenerational transmission of constructive parenting. Furthermore, the mediating effect of marital relationship is stronger for current fathers than for mothers because of a stronger association between marital satisfaction and constructive parenting for men. The implications are discussed. PMID- 20357902 TI - Conformational changes in receptor tyrosine kinase signaling: an ErbB garden of delights. AB - The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors. PMID- 20357903 TI - Influence of Inner Transducer Properties on EMF Response and Stability of Solid Contact Anion Selective Membrane Electrodes Based on Metalloporphyrin Ionophores. AB - The performance of solid-contact/coated wire type electrodes with plasticized PVC membranes containing metalloporphyrins as anion selective ionophores is reported. The membranes are deposited on transducers based on graphite pastes and graphite rods. The hydrophobicity of the underlying conductive transducer surface is found to be a key factor that influences the formation of an aqueous layer beneath the polymer film. Elimination of this ill-defined water layer greatly improves the electrochemical properties of the ion-sensors, such as EMF stability and life time. Only highly lipophilic electrode substrates, namely graphite paste with mineral oil, were shown to prevent the formation of aqueous layer underneath the ion-sensing membrane. The possibility of employing Co(III)-tetraphenylporphyrin both as NO(2) (-) selective ionophore and as electron/ion conducting species to ensure ion-to-electron translation was also discussed based on the results of preliminary experiments. PMID- 20357904 TI - A Novel Application of a Bivariate Regression Model for Binary and Continuous Outcomes to Studies of Fetal Toxicity. AB - Public health concerns over the occurrence of birth defects and developmental abnormalities that may occur as a result of prenatal exposure to drugs, chemicals, and other environmental factors has led to an increasing number of developmental toxicity studies. Because fetal pups are commonly evaluated for multiple outcomes, data analysis frequently involves a joint modeling approach. In this paper, we focus on modelling clustered binary and continuous outcomes in the setting where both outcomes are potentially observable in all offspring but, due to practical limitations, the continuous outcome is only observed in a subset of offspring. The subset is not a simple random sample (SRS) but is selected by the experimenter under a prespecified probability model.While joint models for binary and continuous outcomes have been developed when both outcomes are available for every fetus, many existing approaches are not directly applicable when the continuous outcome is not observed in a SRS. We adapt a likelihood-based approach for jointly modelling clustered binary and continuous outcomes when the continuous response is missing by design and missingness depends on the binary trait. The approach takes into account the probability that a fetus is selected in the subset. Through the use of a partial likelihood, valid estimates can be obtained by a simple modification to the partial likelihood score. Data involving the herbicide 2,4,5-T are analyzed. Simulation results confirm the approach. PMID- 20357905 TI - Synthesis and bio-functionalization of multifunctional magnetic Fe(3)O(4)@Y(2)O(3):Eu nanocomposites. AB - A facile homogenous precipitation method has been developed for the synthesis of multifunctional, magnetic, luminescent nanocomposites with Fe(3)O(4) nanoparticles as the core and europium-doped yttrium oxide (Y(2)O(3):Eu) as the shell. The nanocomposites showed both super-paramagnetic behavior and unique europium fluorescence properties with high emission intensity. Their surface has been modified with a bifunctional ligand, p-aminobenzoic acid (PABA), and further biofunctionalized with biotin; the nanocomposites showed specific targeting for avidin-coupled polystyrene beads. PMID- 20357906 TI - An improved hybrid global optimization method for protein tertiary structure prediction. AB - First principles approaches to the protein structure prediction problem must search through an enormous conformational space to identify low-energy, near native structures. In this paper, we describe the formulation of the tertiary structure prediction problem as a nonlinear constrained minimization problem, where the goal is to minimize the energy of a protein conformation subject to constraints on torsion angles and interatomic distances. The core of the proposed algorithm is a hybrid global optimization method that combines the benefits of the alphaBB deterministic global optimization approach with conformational space annealing. These global optimization techniques employ a local minimization strategy that combines torsion angle dynamics and rotamer optimization to identify and improve the selection of initial conformations and then applies a sequential quadratic programming approach to further minimize the energy of the protein conformations subject to constraints. The proposed algorithm demonstrates the ability to identify both lower energy protein structures, as well as larger ensembles of low-energy conformations. PMID- 20357907 TI - Intrinsic Free Energy of the Conformational Transition of the KcsA Signature Peptide from Conducting to Nonconducting State. AB - We explore a conformational transition of the TATTVGYG signature peptide of the KcsA ion selectivity filter and its GYG to AYA mutant from the conducting alpha strand state into the nonconducting pII-like state using a novel technique for multidimensional optimization of transition path ensembles and free energy calculations. We find that the wild type peptide, unlike the mutant, intrinsically favors the conducting state due to G77 backbone propensities and additional hydrophobic interaction between the V76 and Y78 side chains in water. The molecular mechanical free energy profiles in explicit water are in very good agreement with the corresponding adiabatic energies from the Generalized Born Molecular Volume (GBMV) implicit solvent model. However comparisons of the energies to higher level B3LYP/6-31G(d) Density Functional Theory calculations with Polarizable Continuum Model (PCM) suggest that the nonconducting state might be more favorable than predicted by molecular mechanics simulations. By extrapolating the single peptide results to the tetrameric channel, we propose a novel hypothesis for the ion selectivity mechanism. PMID- 20357908 TI - O Labeling for a Quantitative Proteomic Analysis of Glycoproteins in Hepatocellular Carcinoma. AB - INTRODUCTION: Quantitative proteomics using tandem mass spectrometry is an attractive approach for identification of potential cancer biomarkers. Fractionation of complex tissue samples into subproteomes prior to mass spectrometric analyses increases the likelihood of identifying cancer-specific proteins that might be present in low abundance. In this regard, glycosylated proteins are an interesting class of proteins that are already established as biomarkers for several cancers. MATERIALS AND METHODS: In this study, we carried out proteomic profiling of tumor and adjacent non-cancer liver tissues from hepatocellular carcinoma (HCC) patients. Glycoprotein enrichment from liver samples using lectin affinity chromatography and subsequent (18)O/(16)O labeling of peptides allowed us to obtain relative abundance levels of lectin-bound proteins. As a complementary approach, we also examined the relative expression of proteins in HCC without glycoprotein enrichment. Lectin affinity enrichment was found to be advantageous to quantitate several interesting proteins, which were not detected in the whole proteome screening approach. We identified and quantitated over 200 proteins from the lectin-based approach. Interesting among these were fetuin, cysteine-rich protein 1, serpin peptidase inhibitor, leucine rich alpha-2-glycoprotein 1, melanoma cell adhesion molecule, and heparan sulfate proteoglycan-2. Using lectin affinity followed by PNGase F digestion coupled to (18)O labeling, we identified 34 glycosylation sites with consensus sequence N-X T/S. Western blotting and immunohistochemical staining were carried out for several proteins to confirm mass spectrometry results. CONCLUSION: This study indicates that quantitative proteomic profiling of tumor tissue versus non cancerous tissue is a promising approach for the identification of potential biomarkers for HCC. PMID- 20357909 TI - Surface molecular property modifications for poly(dimethylsiloxane) (PDMS) based microfluidic devices. AB - Fast advancements of microfabrication processes in past two decades have reached to a fairly matured stage that we can manufacture a wide range of microfluidic devices. At present, the main challenge is the control of nanoscale properties on the surface of lab-on-a-chip to satisfy the need for biomedical applications. For example, poly(dimethylsiloxane) (PDMS) is a commonly used material for microfluidic circuitry, yet the hydrophobic nature of PDMS surface suffers serious nonspecific protein adsorption. Thus the current major efforts are focused on surface molecular property treatments for satisfying specific needs in handling macro functional molecules. Reviewing surface modifications of all types of materials used in microfluidics will be too broad. This review will only summarize recent advances in nonbiofouling PDMS surface modification strategies applicable to microfluidic technology and classify them into two main categories: (1) physical approach including physisorption of charged or amphiphilic polymers and copolymers, as well as (2) chemical approach including self assembled monolayer and thick polymer coating. Pros and cons of a collection of available yet fully exploited surface modification methods are briefly compared among subcategories. PMID- 20357910 TI - Effects of assertiveness training and expressive writing on acculturative stress in international students: A randomized trial. AB - International university students often experience acculturative stress, and culturally appropriate techniques to manage stress are needed. This randomized trial tested the effects of group assertiveness training, private expressive writing, their combination, and a wait-list control on the acculturative stress, affect, and health of 118 international students at an urban North American university. Interventions were conducted at the start of a semester, and assessments were conducted at baseline and at the end of the semester. Group assertiveness training was rated positively by students and led to lower negative affect, whereas expressive writing was less well received and led to higher homesickness and fear, but also to higher positive affect. The combined intervention had no effects, perhaps because the 2 components negated each other. It is concluded that group assertiveness training improves emotional adjustment of international students but that expressive writing has mixed effects and needs further development and study. (PsycINFO Database Record PMID- 20357911 TI - Identification of Pirh2D, an Additional Novel Isoform of Pirh2 Ubiquitin Ligase. AB - Pirh2 is an E3 ubiquitin ligase that promotes tumor suppressor p53 ubiquitination and proteasomal degradation. Recently, we have reported the identification and characterization of two novel isoforms of Pirh2 named Pirh2B and Pirh2C and accordingly, reclassified the full-length Pirh2 as Pirh2A. Both Pirh2B and C negatively regulate p53 and also exhibit interactions with MDM2. Here, we report the existence of an additional Pirh2 isoform that we have named Pirh2D. Translation of nucleotide sequence predicts Pirh2D to be composed of 75 amino acids with a molecular mass of 8493.74 Da. Thus, Pirh2D is a truncated protein that harbors 67 amino-terminal amino acids identical to those in Pirh2A, Pirh2B and Pirh2C and has 8 additional unique amino acids at the carboxyl-terminal end. Further studies are needed to determine whether Pirh2D also functions in a manner similar to Pirh2B and Pirh2C. PMID- 20357912 TI - Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis. AB - Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Since current treatments are aimed at nonspecifically down regulating inflammation and natural mechanisms of repair and remyelination within the CNS are inadequate for recovery of function, MS patients presently only have available treatments that delay symptom progression. The complex nature of this disease means that only multifaceted treatments hold the promise of a cure. Recent studies indicate that the ER stress response, a cellular pathway that allows a cell to survive and recover from a stressful event, could be elicited to help the myelin-generating and myelin-support cells of the CNS survive inflammatory insult. PMID- 20357913 TI - Effective depletion of regulatory T cells allows the recruitment of mesothelin specific CD8 T cells to the antitumor immune response against a mesothelin expressing mouse pancreatic adenocarcinoma. AB - Vaccine-induced CD8(+) T-cell responses can eradicate developing tumors in vivo in mouse models. Translating these successes into approved treatments for cancer patients has been challenging, since many of these models lack expression of clinically proven/relevant tumor antigens. We have shown that mesothelin is a clinically relevant CD8(+) T-cell target in human pancreas cancer, which is also highly conserved among species. Here, we utilize the murine mesothelin-expressing pancreatic tumor model (Panc02) to identify the immune-relevant mesothelin derived peptides and study interventions that enhance the antitumor response. We first screened overlapping peptides of the entire murine mesothelin protein to identify two new CD8(+) mesothelin-restricted epitopes. These peptides were then evaluated for recognition by vaccine-induced T cells from mice treated with vaccine in sequence with low-dose cyclophosphamide (CY) and an anti-CD25 IL 2Ralpha monoclonal antibody (PC61). These treatments are both known to deplete subpopulations of T regulatory cells (Tregs). Our findings demonstrate that combined Treg-depleting therapies synergize to enhance vaccine efficacy. Furthermore, our data supports mesothelin as a relevant antigen in murine and clinical models and the use of Panc02 as a clinically relevant murine model of pancreatic cancer for evaluating antigen-targeted immunotherapies in immune tolerant hosts. PMID- 20357914 TI - A mixed ordinal location scale model for analysis of Ecological Momentary Assessment (EMA) data. AB - Mixed-effects logistic regression models are described for analysis of longitudinal ordinal outcomes, where observations are observed clustered within subjects. Random effects are included in the model to account for the correlation of the clustered observations. Typically, the error variance and the variance of the random effects are considered to be homogeneous. These variance terms characterize the within-subjects (i.e., error variance) and between-subjects (i.e., random-effects variance) variation in the data. In this article, we describe how covariates can influence these variances, and also extend the standard logistic mixed model by adding a subject-level random effect to the within-subject variance specification. This permits subjects to have influence on the mean, or location, and variability, or (square of the) scale, of their responses. Additionally, we allow the random effects to be correlated. We illustrate application of these models for ordinal data using Ecological Momentary Assessment (EMA) data, or intensive longitudinal data, from an adolescent smoking study. These mixed-effects ordinal location scale models have useful applications in mental health research where outcomes are often ordinal and there is interest in subject heterogeneity, both between- and within subjects. PMID- 20357915 TI - Recurrent Abdominal Pain in Primary and Tertiary Care: Differences and Similarities. PMID- 20357916 TI - Is melamine contamination an issue in Canada? PMID- 20357917 TI - Kids on kids' health: Creating a child health magazine with students from an urban, multicultural, low-income elementary school. PMID- 20357918 TI - Dr Elizabeth (Lee) Ford-Jones: Closing the book on a decade devoted to the Canadian Paediatric Society journal. PMID- 20357919 TI - Melamine food contamination: Relevance to Canadian children. PMID- 20357920 TI - The role of economic and cultural status as risk indicators for alcohol and marijuana use among adolescents. AB - INTRODUCTION: A number of reports suggest that Aboriginal cultural status is a major risk indicator for drug and alcohol use. The primary purpose of the present paper was to determine whether Aboriginal cultural status is independently associated with risk behaviours, such as marijuana use and alcohol abuse, among youth after multivariate adjustment for other factors, such as socioeconomic status. METHODS: Every student between grades 5 and 8 in Saskatoon, Saskatchewan, was asked to complete a questionnaire in February 2007. Logistic regression was used to determine the independent risk indicators associated with alcohol abuse and marijuana use. RESULTS: Four thousand ninety-three youth participated in the school health survey. At the cross-tabulation level, cultural status and neighbourhood income were both strongly associated with alcohol and marijuana use. After multivariate adjustment, the association between Aboriginal cultural status and alcohol abuse was not statistically significant (crude OR=3.52 to adjusted OR=0.80). For marijuana use, the association was significantly reduced (crude OR=9.91 to adjusted OR=2.79). After controlling for all other variables, results showed that low-income youth were 103% more likely to get drunk at least once and were 163% more likely to have tried marijuana at least once. CONCLUSION: To be more successful, future policies directed toward reducing risk behaviours among youth should consider neighbourhood income characteristics. PMID- 20357921 TI - Diagnosing fetal alcohol spectrum disorder: History, challenges and future directions. AB - Fetal alcohol spectrum disorder (FASD) is one of the most common preventable causes of developmental disability, and is currently one of the most pressing public health concerns in Canada. FASD refers to the range of physical, mental, behavioural and learning disabilities that an individual may acquire as a result of maternal alcohol consumption. In the present paper, the history of the diagnostic approach to alcohol-related disorders over the past 35 years is reviewed. Research supporting the importance of early diagnosis for the long-term outcomes and management of individuals with FASD is presented, and challenges that have plagued efforts to efficiently diagnose individuals with FASD are discussed. Finally, the study reviews the future directions and implications regarding current diagnostic strategies. PMID- 20357923 TI - Vaccination site reaction or bacterial cellulitis? PMID- 20357922 TI - Two hour blood glucose levels in at-risk babies: An audit of Canadian guidelines. AB - BACKGROUND: The Canadian guidelines recommend blood glucose (BG) screening starting at 2 h of age in asymptomatic 'at-risk' babies (including small-for gestational-age [SGA] and large-for-gestational-age [LGA] infants), with intervention cut-offs of 1.8 mmol/L and 2.6 mmol/L. The present study reviews and audits this practice in full-term newborn populations. METHODS: A literature review meta-analyzed BG values in appropriate-for-gestational age (AGA) term newborns to establish normal 1 h, 2 h and 3 h values. A clinical review audited screening of 'at-risk' SGA and LGA term newborns, evaluating both clinical burden and validity. RESULTS: The review included six studies, although none clearly defined the plasma glucose standard. The pooled mean (plasma) BG level in AGA babies 2 h of age was 3.35 mmol/L (SD=0.77), significantly higher than 1 h levels (3.01 mmol/L, SD=0.96). In the audit, 78 SGA and 142 LGA babies each had an average of 6.0 and 4.7 BG tests, respectively. The mean 2 h BG levels for SGA (3.42 mmol/L, SD=1.02) and LGA (3.31 mmol/L, SD=0.66) babies did not differ significantly from the AGA pooled mean. Receiver operating characteristic curves showed that 2 h BG levels in LGA and SGA babies predicted later hypoglycemia (defined as a BG level lower than 2.6 mmol/L), but sensitivities and specificities were poor. CONCLUSIONS: Published 2 h BG levels for AGA babies are higher than 1 h values and are similar to audited 2 h levels in SGA and LGA babies. Clinically, 2 h levels are predictive of later hypoglycemia but may require repeat BG testing. Audit is an important tool to validate national guidelines, to minimize their burden and to maximize their utility. PMID- 20357924 TI - Vision screening in infants, children and youth. PMID- 20357925 TI - High anxiety: recognizing stress as the stressor. PMID- 20357926 TI - Oxidative stress and anxiety: relationship and cellular pathways. AB - High O(2) consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal anxiety and also on a possible causal relationship between cellular oxidative stress and emotional stress. This review examines the recent discoveries made on the link between oxidative status and normal anxiety levels and the putative role of oxidative stress in genesis of anxiety. We discuss the different opinions and questions that exist in the field and review the methodological approaches that are being used to determine a causal relationship between oxidative and emotional stress. PMID- 20357927 TI - Lipid peroxidation and antioxidant status in head and neck squamous cell carcinoma patients. AB - Oxidative stress, a consequence of an imbalance between the formation and inactivation of reactive oxygen species, may be involved in the pathogenesis of many diseases including cancer. To evaluate the magnitude of oxidative stress, a study on the plasma levels of superoxide dismutase, total thiols, ascorbic acid and malondialdehyde (MDA) has been done in head and neck squamous cell carcinoma patients before the start of any oncological treatment and compared with healthy controls. The specific activity of superoxide dismutase in cancer patients is decreased significantly when compared to the control (p < 0.05). The total thiol and ascorbic acid levels are significantly reduced (p < 0.005) whereas MDA levels are significantly increased in the patients (p < 0.00005). Our findings show that the oxidative stress is elevated in cancer patients as evidenced by elevated levels of lipid peroxidation products and depletion of enzymatic and non enzymatic antioxidants. PMID- 20357928 TI - Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine. AB - The testis is an immunologically privileged organ. Sertoli cells can form a blood testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2(nd) group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients. PMID- 20357929 TI - Specific factors influence the success of autologous and allogeneic hematopoietic stem cell transplantation. AB - Successful hematopoietic stem cell transplantation (HSCT), both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/microL) and platelet (>20,000/microL) reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT) and 40 allogeneic bone marrow transplantation (BMT) patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00) and 19.00 (16.00/23.00) and platelet on day 11.00 (10.00/13.00) and 21.00 (18.00/25.00), respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM) and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD) and aplastic anemia (AA) and MM presented the best overall survival (OS) in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR), where CBV, melphalan (M-200) and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50-59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery. PMID- 20357930 TI - Pineal proteins upregulate specific antioxidant defense systems in the brain. AB - The neuroendocrine functions of the pineal affect a wide variety of glandular and nervous system processes. Beside melatonin (MEL), the pineal gland secretes and expresses certain proteins essential for various physiological functions. It has been suggested that the pineal gland may also have an antioxidant role due to secretory product other than MEL. Therefore, the present study was designed to study the effect of buffalo (Bubalus bubalis) pineal proteins (PP) on the antioxidant defense system in the brain of female rats. The twenty-four rats were taken in present study and were divided into four groups: control (0 day), control (28 day), vehicle control and buffalo PP. The PP was injected 100 MUg/kg BW intraperitoneal (i.p.) daily for 28 days. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) and reduced glutathione (GSH) concentration and the levels of lipid peroxidation (LPO) in the brain tissue were measured to assess the antioxidant systems. These enzymes protect from adverse effects of free radicals and help in amelioration of oxidative stress. Buffalo pineal proteins administration did not cause any effect on brain LPO, whereas GPx, GR and GSH were significantly (p < 0.05) decreased. However, SOD and CAT activities were increased to significant levels than the control in PP treated rats. Our study herein suggested that buffalo (Bubalus bubalis) pineal proteins upregulates specific antioxidant defense systems and can be useful in control of various oxidative stress-induced neuronal diseases. PMID- 20357931 TI - Urate oxidase knockdown decreases oxidative stress in a murine hepatic cell line. AB - Humans, birds, and some primates do not express the uric acid degrading enzyme urate oxidase (UOX) and, as a result, have plasma uric acid concentrations higher than UOX expressing animals. Although high uric acid concentrations are suggested to increase the antioxidant defense system and provide a health advantage to animals without UOX, knockout mice lacking UOX develop pathological complications including gout and kidney failure. As an alternative to the knockout model, RNA interference was used to decrease UOX expression using stable transfection in a mouse hepatic cell line (ATCC, FL83B). Urate oxidase mRNA was reduced 66% (p < 0.05) compared to wild type, as measured by real time RT-PCR. To determine if UOX knockdown resulted in enhanced protection against oxidative stress, cells were challenged with hexavalent chromium (Cr(VI)) or 3-morpholinosydnonimine hydrochloride (SIN-1). Compared to wild type, cells with UOX knockdown exhibited a 37.2 +/- 3.5% reduction (p < 0.05) in the electron spin resonance (ESR) signal after being exposed to Cr(VI) and displayed less DNA fragmentation (p < 0.05) following SIN-1 treatment. Cell viability decreased in wild type cells (p < 0.05), but not cells with UOX knockdown, after treatment with SIN-1. These results are consistent with an increased intracellular uric acid concentration and an increased defense against oxidative stress. PMID- 20357933 TI - Iron toxicity: new conditions continue to emerge. AB - During the past half century, excessive/misplaced iron has been observed to be a risk factor for an increasing number and diversity of disease conditions. An extensive list of conditions and of the types of iron association were published in early 2008. Within the subsequent year, four additional disorders have been recognized to be enhanced by iron: aging muscle atrophy, viral replication, rosacea and pulmonary alveolar proteinosis. This paper adds new data and emphasis on these disorders as entities associated with increased iron load and toxicity. PMID- 20357932 TI - Implications for degenerative disorders: antioxidative activity, total phenols, flavonoids, ascorbic acid, beta-carotene and beta-tocopherol in Aloe vera. AB - In order to demonstrate whether the known biological effects of Aloe vera (L.) Burm. fil. could correlate with the antioxidant activity of the plant, the antioxidant activity of the aqueous leaf extract was investigated. The present study demonstrated that the aqueous extract from A. vera leaves contained naturally occuring antioxidant components, including total phenols, flavonoids, ascorbic acid, beta-carotene and alpha-tocopherol. The extract exhibited inhibitory capacity against Fe(3+)/ascorbic acid induced phosphatidylcholine liposome oxidation, scavenged stable DPPH(*), ABTS(*+) and superoxide anion radicals, and acted as reductant. In contrast, the leaf inner gel did not show any antioxidant activity. It was concluded that the known beneficial effects of Aloe vera could be attributed to its antioxidant activity and could be related to the presence of phenolic compounds and antioxidant vitamins. PMID- 20357935 TI - MAP in the environment of dairy herds - a comment. PMID- 20357934 TI - Excitotoxic insults lead to peroxiredoxin hyperoxidation. AB - Post-mitotic neurons must have strong antioxidant defenses to survive the lifespan of the organism. We recently showed that neuronal antioxidant defenses are boosted by synaptic activity. Elevated synaptic activity, acting via the N methyl-D-aspartate (NMDA) receptor, enhances thioredoxin activity, facilitates the reduction of hyperoxidized peroxiredoxins, and promotes resistance to oxidative stress. In contrast, blockade of spontaneous synaptic NMDA receptor activity renders neurons highly sensitive to hyperoxidation of peroxiredoxins by oxidative insults. These NMDA receptor-dependent effects are mediated in part by a coordinated program of gene expression changes centered on the thioredoxin peroxiredoxin system, a thiol-based enzymatic system which is an important reducer of oxidative stressors such as hydroperoxides. We show here that while too little glutamatergic activity can render neurons vulnerable to peroxiredoxin hyperoxidation, so can too much. Exposure of neurons to toxic concentrations of glutamate, activating both synaptic and extrasynaptic NMDA receptors, acutely induces peroxiredoxin hyperoxidation. Thus, the effect of NMDA receptor activity on the activity of neuronal peroxiredoxins follows the classical U-shaped dose response curve. PMID- 20357940 TI - An ethicist's commentary on euthanasia in difficult circumstances. PMID- 20357941 TI - Use of thyroid stimulating hormone (TSH) in cats. PMID- 20357942 TI - The new influenza A H1N1 virus: balancing on the interface of humans and animals. AB - In the spring of 2009, a new human influenza A H1N1 virus emerged in Mexico and the United States. The strain was referred to as "swine flu" as it has strong similarities with current circulating swine influenza viruses, although the first outbreak on a swine farm was recorded more than 2 mo following the first human reports. This new strain, designated as pandemic (H1N1) 2009, has shown the ability to spread amongst the human population and can be found on all continents. The way influenza viruses and specifically this influenza A pandemic (H1N1) 2009 virus evolve is described in this manuscript. PMID- 20357943 TI - Canine hypoadrenocorticism: part I. AB - Hypoadrenocorticism (Addison's disease) has been referred to as "the great pretender," due to its ability to mimic other common diseases in the dog and thereby represent a diagnostic challenge. Naturally occurring hypoadrenocorticism is an uncommon canine disease. Young, female dogs are overrepresented. Hypoadrenocorticism typically results from immune-mediated destruction of all adrenocortical layers, resulting in deficiencies of min-eralocorticoids (aldosterone) and glucocorticoids (cortisol). A small number of dogs suffer from glucocorticoid deficiency only. Dogs suffering from hypoadrenocorticism may present in a variety of conditions, from a mildly ill dog to a shocky and recumbent dog. This review discusses etiology, pathophysiology, history, physical examination findings, and diagnostic findings in the Addisonian patient. A follow up article (Part II) will discuss the definitive diagnosis and management strategies for these patients. PMID- 20357944 TI - Mortality and morbidity associated with gunshot in raptorial birds from the province of Quebec: 1986 to 2007. AB - Although raptors have been protected for decades in Quebec they are still regular victims of poaching. The objective of this study was to characterize cases of raptor shootings in Quebec over the last 2 decades. We reviewed clinical files, radiographs, and pathology reports on 4805 free-flying birds of prey admitted to the Faculte de medecine veterinaire between 1986 and 2007. Evidence of gunshots was detected in 6.4% of the birds. Large species, such as ospreys, turkey vultures, snowy owls, and bald eagles represented the most frequently targeted species. The percentage of shot birds has decreased from 13.4% during 1991 to 1992 to 2.2% in 2006 to 2007. Potential reasons for this trend include a decrease in the presence of firearms in raptor habitats and changes in human attitude towards raptorial birds. PMID- 20357945 TI - A survey of Aleutian mink disease virus infection of feral American mink in Nova Scotia. AB - Spleen samples from 14 mink that were trapped in 4 counties of Nova Scotia were tested for the presence of the Aleutian mink disease virus (AMDV) by polymerase chain reaction. Viral DNA was not detected in samples from Kings County (n = 2), but was detected in all the mink sampled from Colchester (n = 2) and Halifax (n = 6) counties, and 3 of 4 mink from Yarmouth County. The high level of AMDV infected mink in Colchester and Halifax counties may pose a serious threat to the captive mink and wild animal populations. Because treatment of infected free ranging mink is not an option, AMDV control strategies for the captive mink should be primarily focused on bio-security to protect clean ranches. PMID- 20357947 TI - Chronic mesenteric volvulus in a dog. AB - A chronic, partial mesenteric volvulus was found on laparotomy of an adult Bernese mountain dog with a 4-month history of intermittent vomiting, diarrhea, and weight loss. The dog had elevated cholestatic and hepatocellular leakage enzymes, increased bile acids, azotemia, isosthenuria, and a hypokalemic, hypochloremic, metabolic alkalosis. The dog recovered fully following reduction of the volvulus. PMID- 20357946 TI - Clonality and phenotyping of canine lymphomas before chemotherapy and during remission using polymerase chain reaction (PCR) on lymph node cytologic smears and peripheral blood. AB - Polymerase chain reaction (PCR) assays for the immunoglobulin and T-cell receptor genes were utilized to determine phenotype and clonality from lymph node cytologic smears and peripheral blood lymphocytes from 10 dogs with lymphoma, before chemotherapy and during remission. Results were compared with those from 13 dogs with a cytologic diagnosis of lymph node hyperplasia. Clonality was identified in 7 of the lymphomas on the basis of either lymph node cytology or peripheral blood lymphocytes before treatment. No lymph node hyperplasia samples were clonal. In 6 of the dogs with lymphoma, clonality was demonstrated during clinical remission. Detection of PCR clonality during clinical remission is an effective means of identifying minimal residual disease in canine lymphoma and thus additional work is warranted to determine if molecular remission is prognostic or predictive for outcome in well-controlled and well-defined lymphoma subtypes. PMID- 20357950 TI - Diagnostic ophthalmology. PMID- 20357949 TI - Syringomyelia in the Cavalier King Charles spaniel (CKCS) dog. PMID- 20357951 TI - Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin. AB - Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects. PMID- 20357952 TI - Characterization of Salmonella Typhimurium isolates associated with septicemia in swine. AB - Salmonella Typhimurium is frequently isolated from pigs and may also cause enteric disease in humans. In this study, 33 isolates of S. Typhimurium associated with septicemia in swine (CS) were compared to 33 isolates recovered from healthy animals at slaughter (WCS). The isolates were characterized using phenotyping and genotyping methods. For each isolate, the phage type, antimicrobial resistance, and pulsed-field gel electrophoresis (PFGE) DNA profiles were determined. In addition, the protein profiles of each isolate grown in different conditions were studied by Coomassie Blue-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot. Various phage types were identified. The phage type PT 104 represented 36.4% of all isolates from septicemic pigs. Resistance to as many as 12 antimicrobial agents, including some natural resistances, was found in isolates from CS and WCS. Many genetic profiles were identified among the PT 104 phage types. Although it was not possible to associate one particular protein with septicemic isolates, several highly immunogenic proteins, present in all virulent isolates and in most isolates from clinically healthy animals, were identified. These results indicated that strains associated with septicemia belong to various genetic lineages that can also be recovered from asymptomatic animals at the time of slaughter. PMID- 20357953 TI - Identification and differentiation of Taylorella equigenitalis and Taylorella asinigenitalis by lipopolysaccharide O-antigen serology using monoclonal antibodies. AB - Lipopolysaccharides (LPSs) from Taylorella equigenitalis, the causative agent of contagious equine metritis, and T. asinigenitalis were compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Lipopolysaccharide profiles of 11 T. equigenitalis strains were similar, but different from the profiles of 3 T. asinigenitalis strains, and the profiles of 2 T. asinigenitalis strains were similar to each other. The serological specificities of the LPSs from these 14 strains were examined by immunoblotting and enzyme-linked immunosorbent assay with monoclonal antibodies (MAbs) to the LPSs of the T. equigenitalis and T. asinigenitalis type strains and T. asinigenitalis strain 2329-98. A MAb to T. equigenitalis LPS O-polysaccharide (O-PS) (M2560) reacted with LPSs from all T. equigenitalis strains but did not react with LPSs from the 3 T. asinigenitalis strains or with 43 non-Taylorella bacteria. Three MAbs to the T. asinigenitalis type strain LPS O-PS or core epitopes (M2974, M2982, M3000) reacted with the homologous strain and T. asinigenitalis strain Bd 3751/05, but not with any of the other bacteria. Five MAbs to T. asinigenitalis 2329-98 LPS O PS or core epitopes (M2904, M2907, M2910, M2923, M2929) reacted only with this strain. Proton nuclear magnetic resonance spectra of the O-PSs of the type strains of T. equigenitalis and T. asinigenitalis provided fingerprint identification and differentiation of these 2 organisms. The serological results were consistent with our previous finding that the O-antigen of the type strain of T. equigenitalis, being a linear polymer of disaccharide repeating [-->4) alpha-L-GulpNAc3NAcA-(1-->4)-beta-D-ManpNAc3NAcA-(1-->] units, differs from that of the T. asinigenitalis O-antigen polymer that is composed of repeating [-->3) beta-D-QuipNAc4NAc-(1-->3)-beta-D-GlcpNAmA-(1-->] units. Lipopolysaccharide O-PS could be a specific marker for identification and differentiation of T. equigenitalis and T. asinigenitalis, and provide the basis for the development of specific detection assays for T. equigenitalis. PMID- 20357954 TI - Protective potential of an attenuated Pasteurella multocida, which expresses only the N-terminal truncated fragment of P. multocida toxin. AB - Pasteurella multocida serogroup D causes progressive atrophic rhinitis in pigs and produces a potent, intracellular, mitogenic toxin known as P. multocida toxin (PMT), which is encoded by the toxA gene. Highly toxic to cells, PMT is a poor antigen and becomes more immunogenic after its native structure has been destroyed. Previously, we found that the N-terminal fragment of PMT (N-PMT) can induce a strong immune response that is protective against wild-type challenge. Here, an attenuated P. multocida mutant expressing only N-PMT was developed and its protective effect was evaluated. The mutant provides protective immune responses against bacterial and toxin challenges, and so is a good live vaccine candidate. PMID- 20357955 TI - Activation of the ovine hypothalamic-pituitary-adrenal axis and febrile response by interleukin-6: a comparative study with bacterial lipopolysaccharide endotoxin. AB - Sheep were subjected to immune challenge with either recombinant human interleukin-6 (rhIL-6; 2.0 microg/kg; n = 5), Escherichia coli lipopolysaccharide (LPS) endotoxin (400 ng/kg; n = 7), or saline (n = 6) to determine if IL-6 activates the febrile and hypothalamic-pituitary-adrenal axis (HPAA) responses in sheep, and to compare these responses with those associated with endotoxemia. Blood was collected over time to measure plasma adrenocorticotropic hormone (ACTH) and serum cortisol concentrations as indicators of HPAA activity. Unlike LPS, rhIL-6 was not pyrogenic in sheep at this challenge dose. In contrast, rhIL 6 elicited ACTH and cortisol responses that peaked earlier than those induced by LPS. These results suggest that this dose of IL-6, alone, is not sufficient to elicit the febrile response in sheep, however, it is a potent activator of the ovine HPAA response. PMID- 20357956 TI - The effect of body position, sedation, and thoracic bandaging on functional residual capacity in healthy deep-chested dogs. AB - The objective of this study was to determine the effect of body position, chest wrap, and sedation on functional residual capacity (FRC) in 6 healthy dogs. Functional residual capacity was determined by helium dilution (re-breathing) whilst in different clinically relevant conditions. These conditions included the standing (sternal) and lateral positions in unsedated dogs and then again both standing and lateral following chest bandaging, and sedation with acepromazine, IV and butorphanol, IV. The mean FRC at each measurement point was determined, as was the change in FRC (delta FRC) from one measurement point to another. Analysis of variance (ANOVA) with repeated measures with Fisher's LSD post hoc test was used to evaluate the effect of interventions. The differences in delta FRC were evaluated using a t-test or Wilcoxon rank-sum test. P < 0.05 was considered significant. The mean FRC at baseline, defined as standing, unsedated and unwrapped, was 75.3 +/- 23.8 mL/kg. Body position or sedation had the most profound effect on FRC with right lateral recumbency lowering FRC by a median of 20.4 mL/kg and sedation lowering FRC by a median of 19.8 mL/kg. Common clinical procedures and positioning result in lowered FRC in healthy deep-chested dogs. In critically ill or injured dogs, the iatrogenic loss of FRC through chest bandaging, sedation, or body position may be clinically relevant. PMID- 20357957 TI - Degradation of foot-and-mouth disease virus during composting of infected pig carcasses. AB - The objective of this study was to investigate the inactivation and degradation of foot-and-mouth disease (FMD) virus during composting of infected pig carcasses as measured by virus isolation in tissue culture and by real-time reverse transcriptase polymerase chain reaction (RRT-PCR). Three FMD-infected pig carcasses were composted in a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. Compost temperatures had reached 50 degrees C and 70 degrees C by days 10 and 19, respectively. Under these conditions, FMD virus was inactivated in specimens in compost by day 10 and the viral RNA was degraded in skin and internal organ tissues by day 21. In comparison, at ambient temperatures close to 20 degrees C, FMD virus survived to day 10 in the skin tissue specimen from the pig that had the highest initial level of viral RNA in its tissues and the viral RNA persisted to day 21. Similarly, beta-actin mRNA, tested as a PCR control, persisted to day 21 in specimens held at ambient temperatures, but it was degraded in the remnants of tissues recovered from compost on day 21. Results from this study provide evidence that composting could be used for safe disposal of pig carcasses infected with FMD virus. PMID- 20357959 TI - Increased risk of chronic wasting disease in Rocky Mountain elk associated with decreased magnesium and increased manganese in brain tissue. AB - Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of Rocky Mountain elk in North America. Recent studies suggest that tissue and blood mineral levels may be valuable in assessing TSE infection in sheep and cattle. The objectives of this study were to examine baseline levels of copper, manganese, magnesium, zinc, selenium, and molybdenum in the brains of Rocky Mountain elk with differing prion genotypes and to assess the association of mineral levels with CWD infection. Elk with leucine at prion position 132 had significantly lower magnesium levels than elk with 2 copies of methionine. Chronic wasting disease-positive elk had significantly lower magnesium than control elk. The incorporation of manganese levels in addition to magnesium significantly refined explanatory ability, even though manganese alone was not significantly associated with CWD. This study demonstrated that mineral analysis may provide an additional disease correlate for assessing CWD risk, particularly in conjunction with genotype. PMID- 20357960 TI - Kinetics and role of antibodies against intimin beta in colostrum and in serum from goat kids and longitudinal study of attaching and effacing Escherichia coli in goat kids. AB - The presence of antibodies to the intimin beta-binding region (Int280-beta) of attaching and effacing Escherichia coli (AEEC) in serum from 20 goat kids from 2 herds, as well as in goat colostrum, was investigated by enzyme-linked immunosorbent assay. In addition, the onset and subsequent pattern of shedding of AEEC from the same goat kids over a 6-mo period was investigated. All the colostrum and serum samples tested contained antibodies against Int280-beta. The association between the antibody titer and the isolation of AEEC suggests that antibodies to intimin beta do not prevent colonization of the intestine by AEEC in goat kids. The AEEC were generally shed only transiently. Most AEEC isolated from the kids belonged to serogroup O26. Three isolates belonged to serogroup O157. These data show that goat kids may be a reservoir of AEEC that are potentially pathogenic for humans. PMID- 20357958 TI - Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses. AB - Endotoxemia causes significant mortality and morbidity in horses. The mechanisms underlying this complex pathophysiology remain unclear. Therefore, effective tools to treat endotoxemia in horses are lacking. Furthermore, the multifactorial and multiorgan pathophysiology of equine endotoxemia has not been fully addressed, especially the lung injury associated with endotoxemia. Within the context of the broader picture of endotoxemia and lung injury, we offer a perspective on the roles of pulmonary intravascular macrophages in endotoxin induced lung inflammation in horses. PMID- 20357961 TI - Isolation of Escherichia coli from piglets in South Korea with diarrhea and characteristics of the virulence genes. AB - Escherichia coli was isolated from the feces of 122 piglets with diarrhea on 55 farms in Korea. The virulence genes of each isolate were characterized by polymerase chain reaction (PCR). Of the 562 isolates, 191 carried 1 or more of the virulence genes tested for in this study. Of the 191 isolates, 114 (60%) carried 1 or more of the genes for enterotoxigenic E. coli (ETEC) fimbriae F4, F5, F6, F18, and F41 and ETEC toxins LT, STa, and STb, 57 (30%) carried 1 or more of the genes for the Shiga-toxin-producing E. coli (STEC) toxins Stx1, Stx2, and Stx2e, and 21% and 37% carried the gene for enteropathogenic E. coli intimin and for enteroaggregative E. coli toxin, respectively. Collectively, our results indicate that other pathotypes of E. coli as well as ETEC can be strongly associated with diarrhea in piglets. In addition, detection of the genes for Stx1 and Stx2 indicates that pigs are reservoirs of human pathogenic STEC. PMID- 20357962 TI - Pleiotropic effects of polysaccharide capsule loss on selected biological properties of Streptococcus suis. AB - In this study, an unencapsulated Streptococcus suis mutant was used to investigate the pleiotropic effects resulting from capsule loss. The capsule deficient mutant of S. suis acquired a biofilm-positive phenotype, which was associated with significantly increased cell surface hydrophobicity. Cell associated fibrinogen-binding and chymotrypsin-like activities were decreased in the unencapsulated mutant. The mutant did not differ significantly from the encapsulated parent strain for minimal inhibitory concentrations to penicillin G, ampicillin, and tetracycline. However, while the encapsulated strain was highly resistant to the bactericidal action of penicillin G and ampicillin, the unencapsulated mutant was approximately 60-fold more sensitive. Compared with the parent strain, the unencapsulated mutant induced a much higher inflammatory response in monocyte-derived macrophages resulting in an increased secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8. The capsule appears to hinder important adhesins or hydrophobic molecules that mediate biofilm formation, as well as cell wall components capable of stimulating immune cells. PMID- 20357963 TI - Rapid serodiagnosis with the use of surface plasmon resonance imaging for the detection of antibodies against major surface protein A of Mycoplasma synoviae in chickens. AB - Mycoplasma synoviae, a major worldwide pathogen in poultry, causes respiratory tract infection and arthritis in chickens and turkeys. Two major surface antigens of M. synoviae are encoded by a single gene, vlhA (variably expressed lipoprotein and hemagglutinin). The gene product is cleaved post-translationally to yield the lipoprotein major surface protein (MSP) B (MSPB) and the hemagglutinin MSPA. The availability of MSPA as an antigen for serodiagnosis was studied by means of a protein chip based on surface plasmon resonance imaging (SPRi). The diagnostic potential of SPRi for measurement of levels of antibody to MSPA was compared with that of a conventional enzyme-linked immunosorbent assay (ELISA) kit. The results from SPRi, a process that took only 1 h, were similar to those from ELISA. Therefore, MSPA can be used as an antigen for serologic studies, and SPRi, a label-free and high-throughput method, may be a valuable tool in avian serodiagnostic studies. PMID- 20357964 TI - Bighorn sheep fetal lung cell line for detection of respiratory viruses. AB - Pneumonia is an important disease of bighorn sheep (BHS) that is primarily responsible for the drastic decline in numbers of these animals in North America. Members of the genus Mannheimia and Pasteurella have frequently been isolated from the pneumonic lungs of BHS. Antibodies to several respiratory viruses, including bovine parainfluenza virus 3 (BPIV-3), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea virus (BVDV), and bovine herpesvirus 1 (BoHV 1), have been detected in herds of BHS. The availability of BHS fetal lung cell lines is likely to enhance the chances of isolation of these viruses. Here we report the development of such a cell line. This line is permissive for BPIV-3, BRSV, BVDV, and BoHV-1 infection, as revealed by an enzyme immunoassay of virus infected cells with antibodies specific for each of these viruses. This cell line should be valuable for detecting these 4, and possibly other, respiratory viruses in BHS. PMID- 20357965 TI - Influence of parity and litter size on gestation length in beagle dogs. AB - This study was conducted to investigate the effects of parity and litter size on gestation length in beagle bitches. The mean duration of the initial elevation (>2 ng/mL) in progesterone concentrations after the onset of proestrus was shorter (P < 0.05) in bitches without (nulliparous) whelping experience than in bitches with (multiparous) whelping experience (6.9 d versus 8.0 d). When calculated as the interval between the day of initial elevation in progesterone concentrations and the day of whelping, the gestation length in the nulliparous bitches was noted to be similar to that in the multiparous bitches (64.3 d versus 64.2 d). No significant correlation between gestation length and litter size was observed in any of the bitches. Our results indicate that the gestation length in beagle bitches is not affected by parity or litter size. PMID- 20357976 TI - Sources of variability among replicate samples separated by two-dimensional gel electrophoresis. AB - Two-dimensional gel electrophoresis (2DE) offers high-resolution separation for intact proteins. However, variability in the appearance of spots can limit the ability to identify true differences between conditions. Variability can occur at a number of levels. Individual samples can differ because of biological variability. Technical variability can occur during protein extraction, processing, or storage. Another potential source of variability occurs during analysis of the gels and is not a result of any of the causes of variability named above. We performed a study designed to focus only on the variability caused by analysis. We separated three aliquots of rat left ventricle and analyzed differences in protein abundance on the replicate 2D gels. As the samples loaded on each gel were identical, differences in protein abundance are caused by variability in separation or interpretation of the gels. Protein spots were compared across gels by quantile values to determine differences. Fourteen percent of spots had a maximum difference in intensity of 0.4 quantile values or more between replicates. We then looked individually at the spots to determine the cause of differences between the measured intensities. Reasons for differences were: failure to identify a spot (59%), differences in spot boundaries (13%), difference in the peak height (6%), and a combination of these factors (21). This study demonstrates that spot identification and characterization make major contributions to variability seen with 2DE. Methods to highlight why measured protein spot abundance is different could reduce these errors. PMID- 20357975 TI - Problems with multiple use of transfer buffer in protein electrophoretic transfer. AB - Two-dimensional gel electrophoresis (2DE) and SDS-PAGE are the two most useful methods in protein separation. Proteins separated by 2DE or SDS-PAGE are usually transferred to membranes using a variety of methods, such as electrophoretic transfer, heat-mediated transfer, or nonelectrophoretic transfer, for specific protein detection and/or analysis. In a recent study, Pettegrew et al. claim to reuse transfer buffer containing methanol for at least five times for transferring proteins from SDS-PAGE to polyvinylidene difluoride. They add 150 200 ml fresh transfer solution each time for extended use as a result of loss of transfer buffer. Finally, they test efficiency of each protein transfer by chemiluminescence detection. Here, we comment on this report, as we believe this method is not accurate and useful for protein analysis, and it can cause background binding as well as inaccurate protein analysis. PMID- 20357977 TI - Simultaneous protein expression and modification: an efficient approach for production of unphosphorylated and biotinylated receptor tyrosine kinases by triple infection in the baculovirus expression system. AB - Protein kinases can adopt multiple protein conformations depending on their activation status. Recently, in drug discovery, a paradigm shift has been initiated, moving from inhibition of fully activated, phosphorylated kinases to targeting the inactive, unphosphorylated forms. For identification and characterization of putative inhibitors, also interacting with the latent kinase conformation outside of the kinase domain, highly purified and homogeneous protein preparations of unphosphorylated kinases are essential. The kinetic parameters of nonphosphorylated kinases cannot be assessed easily by standard kinase enzyme assays as a result of their intrinsic autophosphorylation activity. Kinetic binding rate constants of inhibitor-protein interactions can be measured by biophysical means upon protein immobilization on chips. Protein immobilization can be achieved under mild conditions by binding biotinylated proteins to streptavidin-coated chips, exploiting the strong and highly specific streptavidin biotin interaction. In the work reported here, the cytoplasmic domains of insulin receptor and insulin-like growth factor-1 receptor fused to a biotin ligase recognition sequence were coexpressed individually with the phosphatase YopH and the biotin-protein ligase BirA upon triple infection in insect cells. Tandem affinity purification yielded pure cytoplasmic kinase domains as judged by gel electrophoresis and HPLC. Liquid chromatography-mass spectrometry analysis showed the absence of any protein phosphorylation. Coexpression of BirA led to quantitative and site-specific biotinylation of the kinases, which had no influence on the catalytic activity of the kinases, as demonstrated by the identical phosphorylation pattern upon autoactivation and by enzymatic assay. This coexpression approach should be applicable to other protein kinases as well and should greatly facilitate the production of protein kinases in their phosphorylated and unphosphorylated state suitable for enzymatic and biophysical studies. PMID- 20357978 TI - Novel method of single antibiotic selection of cells containing multiple stage specific promoter-fluorophore plasmids. AB - This study demonstrates a novel method by which multiple separate plasmids can be stably integrated into the genome using single antibiotic resistance for selection. This method was used to integrate three different cardiac-specific promoters driving different fluorophores into murine embryonic stem cells, allowing sequential visualization of various stages of cardiac differentiation. This method is broadly applicable to the study of cell lineage of different stem/progenitor cells. PMID- 20357979 TI - Laser-capture microdissection impairs activity-based protein profiles for serine hydrolase in human lung adenocarcinoma. AB - Laser-capture microdissection (LCM) enables the selection of a specific and pure cell population from a heterogenous tissue such as tumors. Activity-based protein profiling/profile (ABPP) is a chemical technology using enzyme-specific active site-directed probes to read out the functional state of many enzymes directly in any proteome. The aim of this work was to assess the compatibility of LCM with downstream ABPP for serine hydrolase (SH) in human lung adenocarcinoma. Fresh frozen lung adenocarcinoma tissue was stained with hematoxylin, toluidine blue, or methyl green (MG). Proteome from stained tissue was labeled further with SH directed probes, and ABPPs were determined on a one-dimensional gel-based approach. This allowed us to assess the impact of staining procedures on their ABPPs. The effect of the LCM process on ABPPs was assessed furthermore using MG stained lung adenocarcinoma tissue. The staining procedures led to strong changes in ABPPs. However, MG staining seemed the most compatible with downstream ABPP. MG-stained, laser-captured, microdissected tissue showed additional change in profiles as a result of the denaturing property of extraction buffer but not to the microdissection process itself. LCM staining procedures but not microdissection per se interfered with downstream ABPP and led to a strong change in ABPPs of SHs in human lung adenocarcinoma. PMID- 20357980 TI - Cost (non)-recovery by platform technology facilities in the Bio21 Cluster. AB - Platform technologies (PT) are techniques or tools that enable a range of scientific investigations and are critical to today's advanced technology research environment. Once installed, they require specialized staff for their operations, who in turn, provide expertise to researchers in designing appropriate experiments. Through this pipeline, research outputs are raised to the benefit of the researcher and the host institution. Platform facilities provide access to instrumentation and expertise for a wide range of users beyond the host institution, including other academic and industry users. To maximize the return on these substantial public investments, this wider access needs to be supported. The question of support and the mechanisms through which this occurs need to be established based on a greater understanding of how PT facilities operate. This investigation was aimed at understanding if and how platform facilities across the Bio21 Cluster meet operating costs. Our investigation found: 74% of platforms surveyed do not recover 100% of direct operating costs and are heavily subsidized by their home institution, which has a vested interest in maintaining the technology platform; platform managers play a major role in establishing the costs and pricing of the facility, normally in a collaborative process with a management committee or institutional accountant; and most facilities have a three-tier pricing structure recognizing internal academic, external academic, and commercial clients. PMID- 20357981 TI - Development of a membrane-bound random DNA sequence combinatorial array recognition surface (CARS). AB - A partially overlapping population of random sequence 60mer DNA molecules consisting of many concatamers of varied lengths was spatially separated in one and two dimensions by electrophoresis in polyacrylamide and transferred to nitrocellulose membranes. The spatially separated library serves as a potential sensor interface on which many different molecular recognition events or target analyte-binding patterns may emerge, thereby theoretically representing a "universal sensor" surface. The separated DNA library has been referred to as a DNA combinatorial array recognition surface or "CARS." After UV baking and various fluorescence staining or fluorescent probe interactions, the one dimensional (1-D) and 2-D membrane-bound CARS were digitally photographed and subjected to image analysis with National Institutes of Health Image-Java software. Image analysis demonstrated relatively consistent and more similar spatial fluorescence patterns within CARS analyte treatment groups but noteworthy pattern differences before and after analyte addition and between different analyte treatments. Taken together, these data suggest a potential role for CARS as a novel, inexpensive, self-assembling universal molecular recognition surface that could be coupled to sophisticated Bayesian or other pattern recognition algorithms to classify analytes or make specific identifications, much like the senses of smell or taste. PMID- 20357984 TI - Toward responsibility in international health: death following treatment in Rockefeller hookworm campaigns, 1914-1934. PMID- 20357982 TI - The comparison of different pre- and post-analysis filters for determination of exon-level alternative splicing events using Affymetrix arrays. AB - Understanding the biologic significance of alternative splicing has been impeded by the difficulty in systematically identifying and validating transcript isoforms. Current exon array workflows suggest several different filtration steps to reduce the number of tests and increase the detection of alternative splicing events. In this study, we examine the effects of the suggested pre-analysis filtration by detection above background P value or signal intensity. This is followed post-analytically by restriction of exon expression to a fivefold change between groups, limiting the analysis to known alternative splicing events, or using the intersection of the results from different algorithms. Combinations of the filters are also examined. We find that none of the filtering methods reduces the number of technical false-positive calls identified by visual inspection. These include edge effects, nonresponsive probe sets, and inclusion of intronic and untranslated region probe sets into transcript annotations. Modules for filtering the exon microarray data on the basis of annotation features are needed. We propose new approaches to data filtration that would reduce the number of technical false-positives and therefore, impact the time spent performing visual inspection of the exon arrays. PMID- 20357985 TI - "Divine stramonium": the rise and fall of smoking for asthma. PMID- 20357986 TI - The case history in medieval Islamic medical literature: Tajarib and Mujarrabat as source. PMID- 20357987 TI - It's probably in the air: medical meteorology in Denmark, 1810-1875. PMID- 20357988 TI - "An all-white institution": defending private practice and the formation of the West African Medical Staff. PMID- 20357989 TI - Major determinants of serum homocysteine concentrations in a Korean population. AB - The objective of this study was to identify the factors that determine serum homocysteine concentrations in Korean population. In a community-based study, 871 participants completed detailed questionnaires and physical examination. We found that increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine significantly increased the risk of hyperhomocysteinemia. However, hormonal and behavioral factors (smoking, alcohol drinking, coffee consumption, and sedentary time) were not associated with the risk of hyperhomocysteinemia. The risk of hyperhomocysteinemia was steeply increased in subjects with two or more risk factors among four selected risk factors (deficiencies of serum folate and vitamin B12, elevated creatinine, and family history of stroke) compared to subjects who did not have any risk factors, especially subjects over the age of 65 yr (odds ratio [OR], 33.5; 95% confidence interval [CI], 3.71-302.0 in men; OR, 39.2; 95% CI, 7.95-193.2 in women). In conclusion, increased age, male sex, family history of stroke, deficiencies of serum folate and vitamin B12, and elevated serum creatinine are important determinants of serum homocysteine concentrations with interaction effects between these factors. PMID- 20357990 TI - Anatomical consideration of the anterior and lateral cutaneous nerves in the scalp. AB - To better understand the anatomic location of scalp nerves involved in various neurosurgical procedures, including awake surgery and neuropathic pain control, a total of 30 anterolateral scalp cutaneous nerves were examined in Korean adult cadavers. The dissection was performed from the distal to the proximal aspects of the nerve. Considering the external bony landmarks, each reference point was defined for all measurements. The supraorbital nerve arose from the supraorbital notch or supraorbital foramen 29 mm lateral to the midline (range, 25-33 mm) and 5 mm below the supraorbital upper margin (range, 4-6 mm). The supratrochlear nerve exited from the orbital rim 16 mm lateral to the midline (range, 12-21 mm) and 7 mm below the supraorbital upper margin (range, 6-9 mm). The zygomaticotemporal nerve pierced the deep temporalis fascia 10 mm posterior to the frontozygomatic suture (range, 7-13 mm) and 22 mm above the upper margin of the zygomatic arch (range, 15-27 mm). In addition, three types of zygomaticotemporal nerve branches were found. Considering the superficial temporal artery, the auriculotemporal nerve was mostly located superficial or posterior to the artery (80%). There were no significant differences between the right and left sides or based on gender (P>0.05). These data can be applied to many neurosurgical diagnostic or therapeutic procedures related to anterolateral scalp cutaneous nerve. PMID- 20357991 TI - Clinical characteristics of monomorphic post-transplant lymphoproliferative disorders. AB - Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD. PMID- 20357992 TI - Infections after living donor liver transplantation in children. AB - The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children. PMID- 20357993 TI - Clinical and radiographic features of adult-onset ankylosing spondylitis in Korean patients: comparisons between males and females. AB - The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4+/-8.9 yr and average disease duration was 9.6+/-6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment. PMID- 20357994 TI - Primary pancreatic lymphoma in Korea--a single center experience. AB - The aim of this study was to report a single center experience of primary pancreatic lymphoma (PPL) in Korea. We analyzed the clinicopathological data from four PPL patients (three male, median age 36 yr) diagnosed from 1997 to 2007 at Seoul National University Hospital. The diagnoses were: diffuse large B cell lymphoma (n=2), Ki-1 (+) anaplastic large cell lymphoma (n=1), and Burkitt lymphoma (n=1). Presenting symptoms and signs were: abdominal pain (n=4), pancreatitis (n=2), weight loss (n=2) and abdominal mass (n=1). No patient underwent surgery. The Ann Arbor stages of the patients were: IEA (n=1), IIEA (n=1), and IVEB (n=2). Two patients underwent treatment. The stage IEA patient underwent chemotherapy and radiation therapy that resulted in a complete remission. The stage IVEB patient who underwent chemotherapy relapsed. This patient underwent subsequent peripheral blood stem cell transplantation and is alive at 30 months. Two patients (stages IVEB and IIEA) without treatment died at 0.8 and 7.0 months, respectively. For PPL patients, chemotherapy-based treatment, and addition of radiation therapy, if possible, may offer good prognosis. PMID- 20357995 TI - Postoperative complications of thyroid cancer in a single center experience. AB - The aim of this study was to investigate the complications following surgical treatment of thyroid cancer and the association between the extent of surgery and complication rates. A total of 2,636 patients who underwent surgery due to thyroid cancer were retrospectively reviewed to identify surgical complications. Complication rates were assessed according to the extent of surgery, which was classified as follows; less-than-total thyroidectomy with central compartment node dissection (CCND) (Group I, n=636), total thyroidectomy with CCND (Group II, n=1,390), total thyroidectomy plus ipsilateral neck dissection (Group III, n=513), and total thyroidectomy plus bilateral neck dissection (Group IV, n=97). The most common surgical complication was symptomatic hypoparathyroidism, of which 28.4% of cases were transient and 0.3% permanent. The other surgical complications included vocal cord palsy (0.7% transient, and 0.2% permanent), hematoma (0.5%), seroma (4.7%), chyle fistula (1.8%), and Horner's syndrome (0.2%). The complication rates increased significantly with increasing the extent of surgery from Group I to Group IV. The more extensive surgery makes more complications, such as hypoparathyroidism, seroma, and others. PMID- 20357996 TI - Long term follow-up results of external beam radiotherapy as primary treatment for retinoblastoma. AB - The authors reviewed their experiences of external beam radiotherapy (EBR) as an initial treatment in retinoblastoma patients to determine its long-term effect on subsequent tumor control and complications. A total of 32 eyes in 25 patients that underwent EBR for retinoblastoma were reviewed retrospectively. The patients consisted of 21 boys and 4 girls of median age at treatment of 7.1 months. Radiation doses ranged from 35 to 59.4 Gy. The 10-yr ocular and patient survivals were 75.4% and 92.3%, respectively. Nine of the 32 eyes progressed; 7 of these were enucleated and 2 were salvaged by focal treatment. According to the Reese Ellsworth classification, 4 of 5 eyes of Group II, 13 of 16 Group III eyes, 2 of 4 Group IV eyes, and 5 of 7 Group V eyes were retained, and of the 32 eyes, 13 had visual acuity better than 20/200. Eleven patients experienced a radiation induced complication. No patient developed a second malignancy during follow-up. Despite the limited number of patients enrolled, EBR may provide a mean of preserving eyeball and vision for some advanced lesions. PMID- 20357997 TI - Necessity of radical hysterectomy for endometrial cancer patients with cervical invasion. AB - To determine whether radical hysterectomy is necessary in the treatment of endometrial cancer patients with cervical involvement, we reviewed the medical records of women who underwent primary surgical treatment for endometrial carcinoma and selected patients with pathologically proven cervical invasion. Among 133 patients, 62 patients underwent extrafascial hysterectomy (EH) and 71 radical or modified radical hysterectomy (RH). The decision regarding EH or RH was made at the discretion of the attending surgeon. The sensitivity of pre operative magnetic resonance imaging for cervical invasion was 44.7% (38/85). In RH patients, 10/71 (14.1%) patients had frankly histologic parametrial involvement (PMI). All were stage III or over. Eight of 10 patients had pelvic/paraaortic node metastasis and two showed extrauterine spread. In 74 patients with stage II cancer, RH was performed in 41 and PMI was not seen. Sixty six (89.2%) patients had adjuvant radiation therapy and there were 3 patients who had developed recurrent disease in the RH group and none in the EH group (Mean follow-up: 51 months). Although these findings cannot conclusively refute or support the necessity of radical hysterectomy in patients with cervical extension, it is noteworthy that the risk of PMI seems to be minimal in patients with a tumor confined to the uterus without evidence of extrauterine spread. PMID- 20357998 TI - IL-10 mediates rosiglitazone-induced kidney protection in cisplatin nephrotoxicity. AB - Cisplatin, a major anti-neoplastic drug, is known to be nephrotoxic and inflammation-inducing. A peroxisome proliferator-activated receptor gamma agonist, regulating lipid metabolism, has known to have anti-inflammatory effect, but the protection mechanisms in various kidney injuries are not fully understood. The purpose of this study was to examine the reno-protective effect of rosiglitazone on cisplatin nephrotoxicity in mice focusing on inflammation and apoptosis. Male BALB/c mice were pretreated with rosiglitazone (10 mg/kg) or vehicle through daily intraperitoneal injection for 3 days and then were given a single injection of cisplatin (20 mg/kg). Cisplatin induced a significant rise in blood urea nitrogen and creatinine levels, and tubular cell damage with marked tissue inflammation. Tissue cytokines and chemokines measured by a cytometric bead array showed increased TNF-alpha, IL-6, MCP-1, and IFN-gamma levels, while IL-10, an anti-inflammatory cytokine, was significantly decreased by cisplatin treatment. However, rosiglitazone pretreatment substantially reversed the depressed IL-10 level with simultaneous suppression of proinflammatory cytokines and chemokines. This tissue cytokine and chemokine milieu was associated with marked attenuation of kidney injury elicited by cisplatin. These findings suggest that the rosiglitazone-mediated renoprotective effect in cisplatin nephrotoxicity of mice is partially mediated by upregulation of anti-inflammatory IL-10 production. PMID- 20357999 TI - Influence of transforming growth factor-beta1 gene polymorphism at codon 10 on the development of cirrhosis in chronic hepatitis B virus carriers. AB - Transforming growth factor (TGF)-beta1 is a key cytokine producing extracellular matrix. We evaluated the effect of TGF-beta1 gene polymorphism at codon 10 on the development of cirrhosis in patients with chronic hepatitis B. One hundred seventy eight patients with chronic hepatitis (CH, n=57) or liver cirrhosis (LC, n=121), who had HBsAg and were over 50 yr old, were enrolled. The genotypes were determined by single strand conformation polymorphism. There were no significant differences in age and sex ratio between CH and LC groups. HBeAg positivity and detection rate of HBV DNA were higher in LC than in CH groups (P=0.055 and P=0.003, respectively). There were three types of TGF-beta1 gene polymorphism at codon 10: proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotype. In CH group, the proportions of P/P, P/L, and L/L genotype were 32%, 51%, and 17%, respectively. In LC group, the proportions of those genotypes were 20%, 47%, and 33%, respectively. The L/L genotype was presented more frequently in LC than in CH groups (P=0.017). Multivariate logistic regression analysis confirms that detectable HBV DNA (odds ratio [OR]: 3.037, 95% confidence interval [CI]: 1.504-6.133, P=0.002) and L/L genotype (OR: 3.408, 95% CI: 1.279-9.085, P=0.014) are risk factors for cirrhosis. PMID- 20358000 TI - Differential expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in thioacetamide-induced chronic liver injury. AB - Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA) induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of alpha smooth muscle actin (alpha-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and alpha-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA. PMID- 20358001 TI - Bioelectrical impedance may predict cell viability during ischemia and reperfusion in rat liver. AB - Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia. PMID- 20358002 TI - Rebamipide may be comparable to H2 receptor antagonist in healing iatrogenic gastric ulcers created by endoscopic mucosal resection: a prospective randomized pilot study. AB - Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H(2) receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers. PMID- 20358003 TI - Effect of recombinant human epidermal growth factor against cutaneous scar formation in murine full-thickness wound healing. AB - A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD 1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta(1) in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta(1), and mediating the formation of collagen. PMID- 20358004 TI - Sympathetic nerve reconstruction for compensatory hyperhidrosis after sympathetic surgery for primary hyperhidrosis. AB - We performed sympathetic nerve reconstruction using intercostal nerve in patients with severe compensatory hyperhidrosis after sympathetic surgery for primary hyperhidrosis, and analyzed the surgical results. From February 2004 to August 2007, sympathetic nerve reconstruction using intercostal nerve was performed in 19 patients. The subjected patients presented severe compensatory hyperhidrosis after thoracoscopic sympathetic surgery for primary hyperhidrosis. Reconstruction of sympathetic nerve was performed by thoracoscopic surgery except in 1 patient with severe pleural adhesion. The median interval between the initial sympathetic surgery and sympathetic nerve reconstruction was 47.2 (range: 3.5-110.7) months. Compensatory sweating after the reconstruction surgery improved in 9 patients, and 3 out of them had markedly improved symptoms. Sympathetic nerve reconstruction using intercostal nerve may be one of the useful surgical options for severe compensatory hyperhidrosis following sympathetic surgery for primary hyperhidrosis. PMID- 20358005 TI - Virulence characteristics and phylogenetic background of ciprofloxacin resistant Escherichia coli in the urine samples from Korean women with acute uncomplicated cystitis. AB - To clarify the characteristics of the virulence factors (VFs) of ciprofloxacin resistant Escherichia coli (CFRE) with acute uncomplicated cystitis (AUC), we determined the VFs and the phylogenetic background of all 54 CFRE strains and the 55 randomly selected ciprofloxacin sensitive E. coli strains (CFSE) from patients with AUC in 22 Korean hospitals. The prevalence of the VFs was as follows: fimA, papEF, papGIII, sfaI, dafaBC, cnf1, and hlyA were presented in 96%, 54%, 68%, 91%, 49%, 72%, and 29% of the samples, respectively. The expressions of papEF, cnf1, and hlyA were significantly more prevalent in the CFSE. Moreover, the expressions of cnf, and papEF significantly reduced the risk of ciprofloxacin resistance. The CFSE was also marginally associated with the group B2 (P=0.05). Although the presence of pyuria and a previous cystitis history were not related with the phylotyping and the expressions of VFs, group B2, and fimA and papEF were more expressed in the younger age patients (P<0.05). In conclusion, the CFRE exhibits a selective loss of VFs and the non-B2 phylotype in Korean AUC patients. The group B2 and the presence of fimA and papEF are associated with a younger age of AUC patients. PMID- 20358006 TI - Neuroanatomical study of periprostatic nerve distributions using human cadaver prostate. AB - We investigated the distribution and navigation of periprostatic nerve fibers and constructed a 3-dimensional model of nerve distribution. A total of 5 cadaver specimens were serially sectioned in a transverse direction with 0.5 cm intervals. Hematoxylineosin staining and immunohistochemical staining were then performed on whole-mount sections. Three representative slides from the base, mid part, and apex of each prostate were subsequently divided into 4 sectors: two lateral, one ventral, and one dorsal (rectal) part. The number of nerve fibers, the distance from nerve fiber to prostate capsule, and the nerve fiber diameters were analyzed on each sector from the representative slides by microscopy. Periprostatic nerve fibers revealed a relatively even distribution in both lateral and dorsal parts of the prostate. There was no difference in the distances from the prostate capsule to nerve fibers. Nerve fibers in the ventral area were also thinner as compared to other areas. In conclusion, periprostatic nerve fibers were observed to be distributed evenly in the periprostatic area, with the exception of the ventral area. As the number of nerve fibers on the ventral part is fewer in comparison, an excessive high up incision is insignificant during the nerve-sparing radical prostatectomy. PMID- 20358007 TI - Platelet serotonin transporter function and heart rate variability in patients with panic disorder. AB - Many studies showed abnormal serotonin transporter (5-HTT) function and heart rate variability (HRV) in panic disorder patients. The present study investigated the relationship between HRV power spectral analysis findings and platelet serotonin uptake in panic disorder patients. Short-term HRV over 5 min and platelet serotonin transporter uptake parameters (V(max) and K(m)) were measured both in 45 patients with panic disorder and in 30 age-matched normal healthy control subjects. Low frequency power (LF) normalized unit (nu) and LF/high frequency power (HF) were significantly higher, whereas HF and HF nu were lower in the patient group than in the control group. V(max) and K(m) were all significantly lower (i.e., reflects decreased 5-HTT function) in patients with panic disorder than in normal controls. In the patient group, K(m) was negatively correlated with LF/HF and LF nu whereas no such correlations between them were found in the control group. By multivariate analysis based on multiple hierarchical linear regression, a low K(m) independently predicted an increased LF nu even after controlling for age, sex, and body mass index in the patient group. These results suggest that impaired 5-HTT function is closely related to dysregulation of autonomic nervous system in panic disorder. PMID- 20358008 TI - Expression profiling of calcium induced genes in cultured human keratinocytes. AB - Terminal differentiation of skin keratinocytes is a vertically directed multi step process that is tightly controlled by the sequential expression of a variety of genes. To examine the gene expression profile in calcium-induced keratinocyte differentiation, we constructed a normalized cDNA library using mRNA isolated from these calcium-treated keratinocytes. After sequencing about 10,000 clones, we were able to obtain 4,104 independent genes. They consisted of 3,699 annotated genes and 405 expressed sequence tags (ESTs). Some were the genes involved in constituting epidermal structures and others were unknown genes that are probably associated with keratinocytes. In particular, we were able to identify genes located at the chromosome 1q21, the locus for the epidermal differentiation complex, and 19q13.1, another probable locus for epidermal differentiation related gene clusters. One EST located at the chromosome 19q13.1 showed increased expression by calcium treatment, suggesting a novel candidate gene relevant to keratinocyte differentiation. These results demonstrate the complexity of the transcriptional profile of keratinocytes, providing important clues on which to base further investigations of the molecular events underlying keratinocyte differentiation. PMID- 20358009 TI - Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia. AB - We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation. PMID- 20358010 TI - Cytomegalovirus ventriculoencephalitis after unrelated double cord blood stem cell transplantation with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia. AB - Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia. PMID- 20358011 TI - Primary squamous cell carcinoma in the testis: a case report. AB - A 51-yr-old man presented with an enlarged right testis for two months. The radically resected testis showed a relatively well-circumscribed ovoid mass, nearly replacing the normal architecture with central cystic changes. Microscopically, the mass was composed of ovoid shaped tumor cells of a moderately differentiated squamous cell carcinoma (SCC). The central portion of the mass was filled with well-formed laminated keratinous materials and the remnant cavity lined by dysplastic squamous epithelium, indicated SCC may be derived from an epidermal cyst. SCC is among the most common types of neoplasm afflicting human beings, but it is rare in the testis. To our knowledge, this is the second report of the testicular squamous cell carcinoma occurring in a patient without other primary tumors, and the firstly reported case in Korea. PMID- 20358012 TI - Transcatheter embolization of a ruptured internal pudendal artery pseudoaneurysm in a patient with neurofibromatosis type 1. AB - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder. Pseudoaneurysms formation and rupture is an unusual complication of neurofibromatosis. To date, pseudoaneurysm of the internal pudendal artery associated with NF-1 has not been reported. In this article, we present a 62-yr old man with NF-1 suffering from spontaneous hematoma of the perinea and scrotum. A digital substraction angiography disclosed a ruptured pseudoaneurysm of the right internal pudendal artery, which was successfully managed with transcatheter embolization. PMID- 20358013 TI - Native coronary artery and grafted artery spasm just after coronary artery bypass grafting: a case report. AB - Native coronary artery spasm after coronary artery bypass grafting (CABG) is scarce. It frequently causes disastrous circulatory collapse. We report a 72-yr old male, who experienced native coronary artery spasm and grafted artery spasm following CABG, which was successfully treated with coronary angiography and intracoronary injection of nitroglycerine. PMID- 20358014 TI - Multiple, bilateral fibroepithelial polyps causing acute renal failure in a gastric cancer patient. AB - We report a case of primary fibroepithelial polyps (FEPs) in the middle of both ureters in a patient with advanced gastric cancer and acute renal failure. Ureteral FEPs are rare benign lesions, and multiple, bilateral lesions are extremely rare. To our knowledge, this report is the seventh case of bilateral FEPs in the literature. Our case has clinical implications because FEPs should be considered as a cause of ureteral obstruction inducing acute renal failure in advanced gastric cancer. PMID- 20358015 TI - Acute shunt malfunction after cesarean section delivery: a case report. AB - Shunt malfunctions that require surgical intervention during pregnancy and the postpartum period are rare. Furthermore, no study has reported on an acute shunt malfunction immediately after cesarean section. Here, we describe the case of a 32-yr-old woman who became drowsy 12 hr after cesarean section delivery of her second child. She had a ventriculoperitoneal shunt placed to treat hydrocephalus associated with meningitis at 26 yr of age. Marked ventriculomegaly was seen on brain computed tomography and her consciousness recovered temporarily after aspirating cerebrospinal fluid from the flushing device. At surgery, the distal catheter tip was plugged by a blood clot. We believe that the blood spilled over during the cesarean section. The clogged catheter end was simply cut off and the remaining catheter was repositioned in the peritoneal cavity. Her consciousness recovered fully. PMID- 20358016 TI - Prophylactic hypogastric artery ballooning in a patient with complete placenta previa and increta. AB - Abnormal attachment of the placenta (Placenta accreta, increta, and percreta) is an uncommon but potentially lethal cause of maternal mortality from massive postpartum hemorrhage. A 33-yr-old woman, who had been diagnosed with a placenta previa, was referred at 30 weeks gestation. On ultrasound, a complete type of placenta previa and multiple intraplacental lacunae, suggestive of placenta accreta, were noted. For further evaluation of the placenta, pelvis MRI was performed and revealed findings suspicious of a placenta increta. An elective cesarean delivery and subsequent hysterectomy were planned for the patient at 38 weeks gestation. On the day of delivery, endovascular catheters for balloon occlusion were placed within the hypogastric arteries, prior to the cesarean section. In the operating room, immediately after the delivery of the baby, bilateral hypogastric arteries were occluded by inflation of the balloons in the catheters previously placed within. With the placenta retained within the uterus, a total hysterectomy was performed in the usual fashion. The occluding balloons were deflated after closure of the vaginal cuff with hemostasis. The patient had stable vital signs and normal laboratory findings during the recovery period; she was discharged six days after delivery without complications. The final pathology confirmed a placenta increta. PMID- 20358018 TI - Clinical characteristics of adult asthma. PMID- 20358019 TI - Prevalence of childhood asthma in Korea: international study of asthma and allergies in childhood. AB - Childhood asthma is a major concern because it leads to more hospital visits and a heavy economic burden. Proper management and prevention strategies for childhood asthma must be based on correct evaluation of prevalence and risk factors for its development. In Korea, nationwide studies were conducted in 1995 and 2000 on students from 68 elementary schools (age, 6-12 years) and junior high schools (age, 12-15 years) by the Korean Academy of Pediatric Allergy and Respiratory Diseases. We used the Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) written and video questionnaires at the same schools during the same period (October-November). The prevalence of asthma in junior high school children seemed to increase over 5 years. However, in elementary school children, the prevalence of asthma symptoms decreased, although the prevalence of 'diagnosis of asthma, ever' and 'treatment of asthma, last 12 months' increased. In addition, it was found that various factors, such as obesity, passive smoking, dietary habits, raising pets at home, and fever/antibiotic use during infancy were associated with childhood asthma. When prevalence of asthma in Korea was compared with that in different regions, the prevalence changes in the 6-7 years age group did not seem to be consistent between regions, whereas similar trends were observed among children aged 13-14 years. To conduct another epidemiological study to evaluate the time trend over time, a third nationwide survey is planned in 2010, and we anticipate ISAAC Phase 3 will explore recent changes in the prevalence of childhood asthma and assess its risk factors in Korean children. On the basis of accurate data on the current status of childhood asthma in 2010, we will be able to establish proper management strategies. PMID- 20358020 TI - The pathophysiology, diagnosis and treatment of allergic rhinitis. AB - Treatment of AR requires a stepwise approach depending on the severity and duration of symptoms. Treatment options for AR consist of allergen avoidance, pharmacotherapy, immunotherapy and surgery. For the mechanisms of AR, anti-IgE antibody and specific antibody to cytokines such as IL-4 or IL-5 that correlate with allergic inflammation have recently emerged. SLIT is currently widely used due to its efficacy, safety and convenience, which replaces subcutaneous immunotherapy. Although allergen avoidance and immunotherapy are theoretically ideal, antihistamines and intranasal corticosteroids will play the main role in the management of AR until an innovative treatment develops. However, patients' main symptom, the duration and severity of AR, patients' compliance, safety of medication and cost-effectiveness should be considered when treatment options are chosen. In conclusion, physicians should be aware of etiology, pathophysiology, symptoms, signs and diseases related to AR in order to make a correct diagnosis and choose a proper treatment option for each patient. PMID- 20358021 TI - Update on the management of antibiotic allergy. AB - Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed. PMID- 20358023 TI - Clinical characteristics according to sensitized allergens in adult korean patients with bronchial asthma. AB - PURPOSE: Allergic sensitization is a risk factor for the development of bronchial asthma. This study was conducted to investigate clinical manifestations according to sensitized allergens in adult Korean patients with bronchial asthma. METHODS: In total, 523 adult patients who were diagnosed with bronchial asthma between March 2002 and March 2008 were included in the study. All patients underwent skin prick tests for approximately 45 allergens or a specific IgE test. Sensitized allergens were grouped into the following categories: house dust mites, fungus, pollen, and animal dander. Atopy was defined as a positive skin prick test response or the presence of a specific IgE to one or more allergens. RESULTS: Of the 523 patients, 295 (56%) were sensitized to one or more allergens. A younger median age, greater proportion of males, higher eosinophil counts, and higher total IgE levels were observed in the atopic asthma group compared to the non atopic asthma group. The PC20 value was negatively correlated with eosinophil counts and total IgE in the atopic asthma group. In the subgroup analysis, patients sensitized to Cladosporium showed poorer pulmonary function and a higher response to bronchodilators. In addition, patients sensitized to Alternaria showed severer bronchial hyperresponsiveness than non-atopic patients with asthma. Finally, a gradual increase in the number of sensitized allergens was noted with increasing age, eosinophil counts, and total IgE levels. CONCLUSIONS: We suggest the need for identifying the existence of atopy and exact offending allergens at the time of asthma diagnosis, since significant differences in sex, age, blood test results, and lung function were observed according to atopy and sensitized allergens. PMID- 20358022 TI - Eosinophil survival and apoptosis in health and disease. AB - Eosinophilia is common feature of many disorders, including allergic diseases. There are many factors that influence the production, migration, survival and death of the eosinophil. Apoptosis is the most common form of physiological cell death and a necessary process to maintain but limit cell numbers in humans and other species. It has been directly demonstrated that eosinophil apoptosis is delayed in allergic inflammatory sites, and that this mechanism contributes to the expansion of eosinophil numbers within tissues. Among the proteins known to influence hematopoiesis and survival, expression of the cytokine interleukin-5 appears to be uniquely important and specific for eosinophils. In contrast, eosinophil death can result from withdrawal of survival factors, but also by activation of pro-apoptotic pathways via death factors. Recent observations suggest a role for cell surface death receptors and mitochondria in facilitating eosinophil apoptosis, although the mechanisms that trigger each of these death pathways remain incompletely delineated. Ultimately, the control of eosinophil apoptosis may someday become another therapeutic strategy for treating allergic diseases and other eosinophil-associated disorders. PMID- 20358024 TI - Asthmatics without rhinitis have more fixed airway obstruction than those with concurrent rhinitis. AB - PURPOSE: Rhinitis and asthma usually occur together. There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. The aim of this study is to evaluate clinical parameters and therapeutic response in patients with between asthma and asthma with AR. METHODS: Four hundred eighty-five patients with asthma and 428 asthmatics with AR, who had lesser than 50 years old and smoked less than 10 pack-years were recruited. We compared FEV1 and FEV1/FVC following bronchodilator, atopy, IgE, emphysema on HRCT, and aspirin intolerance between two groups. Also we compared physiologic fixed airway obstruction defined using FEV1/FVC and FEV1 less than 75% following anti-asthmatic drug for 1 year. RESULTS: 46.8% (428/913) asthmatics suffered from AR. There were no differences of total IgE, body mass index, PC20, sputum eosinophils and emphysema on HRCT between two groups. The age in asthmatics was higher than that in those with AR. FEV1/FVC was lower in asthmatics than in those with AR. The prevalence of atopy was higher in asthmatics with AR than in asthmatics. Aspirin intolerance was higher in asthmatics with AR than in asthmatics (42/218 vs 13/109, P=0.001). Fixed airway obstruction were more observed in asthmatics than in those with AR (39/319 vs 28/355, P=0.001) after anti-asthmatic drug for 1 year. CONCLUSIONS: Asthmatics with AR had more atopy and aspirin intolerance than asthmatics, and asthmatics had poor response to anti inflammatory drugs than those with concurrent rhinitis, indicating that asthmatics have more fixed airway obstruction than those with concurrent rhinitis. PMID- 20358025 TI - Beta-lactam antibiotic sensitization and its relationship to allergic diseases in tertiary hospital nurses. AB - PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi(2)=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi(2)=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi(2)=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23 12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy. PMID- 20358026 TI - Comparison of the causes and clinical features of drug rash with eosinophilia and systemic symptoms and stevens-johnson syndrome. AB - PURPOSE: Drug rash with eosinophilia and systemic symptoms (DRESS) and the Stevens-Johnson syndrome (SJS) are both severe drug reactions. Their pathogenesis and clinical features differ. This study compared the causes and clinical features of SJS and DRESS. METHODS: We enrolled 31 patients who were diagnosed with DRESS (number=11) and SJS (number=20). We retrospectively compared the clinical and laboratory data of patients with the two disorders. RESULTS: In both syndromes, the most common prodromal symptoms were itching, fever, and malaise. The liver was commonly involved in DRESS. The mucosal membrane of the oral cavity and eyes was often affected in SJS. The most common causative agents in both diseases were antibiotics (DRESS 4/11 (37%), SJS 8/20 (40%)), followed by anticonvulsants (DRESS 3/11 (27%), SJS 7/20 (35%)). In addition, dapsone, allopurinol, clopidogrel, sulfasalazine and non-steroidal anti-inflammatory drugs (NSAIDs) were sporadic causes. CONCLUSIONS: The most common causes of DRESS and SJS were antibiotics, followed by anticonvulsants, NSAIDs and sulfonamides. The increase in the use of antibiotics in Korea might explain this finding. PMID- 20358027 TI - Association Between Serum IgE Levels and the CTLA4 +49A/G and FCER1B -654C/T Polymorphisms in Korean Children With Asthma. AB - PURPOSE: T cells play a central role in cell-mediated immunity, atopic disease, and asthma. The balance of CD28/cytotoxic T-lymphocyte antigen 4 (CTLA4)-derived signal transduction plays an important role in the activation of T cells and an increased immunoglobulin E (IgE) response. The aim of the current study was to investigate the association between polymorphisms in the genes encoding both CTLA4 and the high-affinity IgE receptor 1B (FCER1B) and serum IgE levels in Korean children with asthma. METHODS: We enrolled 238 controls and 742 children with asthma. The CTLA4 +49A/G and FCER1B -654C/T polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: We observed no difference in the distribution of CTLA4 +49A/G among controls, children with asthma, and those with atopic asthma. In contrast, the GA genotype of CTLA4 +49A/G in children with atopic asthma was significantly higher compared to that in those with non-atopic asthma. Moreover, significantly higher log Dp/Df specific IgE levels were found in children with asthma and those with atopic asthma carrying one or two copies of the CTLA4 +49A versus those homozygous for +49G. Gene-gene interactions between CTLA4 and FCER1B with the heterozygote and homozygote of variant genotypes were associated with the log Dp/Df-specific IgE levels, but not asthma development. In addition, children with Dp/Df (+) asthma carried an elevated combined genotype of risk allele compared to those with Dp/Df (-) asthma. CONCLUSIONS: The CTLA4 +49A/G polymorphism may contribute to the production of IgE in Korean children with asthma, especially in Dp/Df-specific IgE levels, but not in the direct development of asthma. In addition, Dp/Df specific IgE levels with a FCER1B -654C/T polymorphism may involve additive effects. PMID- 20358028 TI - IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma. AB - PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype 1055C>T (P<0.001) had a significantly higher frequency of rhinosinusitis, as compared to those with the minor alleles of these two single nucleotide polymorphisms. AIA patients with the GG genotype had a higher peripheral eosinophil count (P=0.025) and a higher serum eotaxin-1 level (P=0.044), as compared to patients with the AA genotype IL-13 Arg110Gln (110G>A). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA. PMID- 20358029 TI - A case of occupational rhinitis caused by rice powder in the grain industry. AB - Rice is the major staple food in a large part of the world, especially in Asia. Hypersensitivity reactions to rice are rare. Moreover, cases of occupational allergies induced by inhalation of rice powder are uncommon. We report a 31-year old male with work-related rhinitis and conjunctivitis symptoms caused by occupational exposure to rice powder in the grain industry. He showed positive responses to rice extracts on a skin prick test, and a high level of serum specific IgE to rice was detected by ELISA. Occupational rhinitis was confirmed by a nasal provocation test with rice extracts. An IgE ELISA inhibition test showed cross-creativity between rice and various grass pollen extracts. These findings suggest that the inhalation of rice powder can induce IgE-mediated occupational rhino-conjunctivitis, which may be derived from cross-reactivity to major grass pollens. PMID- 20358030 TI - Smoking-Induced Acute Eosinophilic Pneumonia in a 15-year-old Girl: A Case Report. AB - Acute eosinophilic pneumonia is a very rare disease that is characterized by acute febrile respiratory failure, diffuse bilateral infiltrates on chest X-ray, and eosinophilia in bronchoalveolar lavage fluid in the absence of infection. We present the case of a 15-year-old girl diagnosed with smoking-induced acute eosinophilic pneumonia. A previously healthy young girl with a 1-day history of fever presented with cough, dyspnea, and diffuse bilateral infiltrates on chest X ray. She had started smoking only 3 weeks before presentation. She was diagnosed by bronchoalveolar lavage fluid tests and lung biopsy and dramatically improved after steroid treatment. We emphasize that acute eosinophilic pneumonia must be considered when acute pneumonia does not respond to broad-spectrum antibiotics. Effective treatment and prompt institution of therapy can obviate unnecessary morbidity and mortality. PMID- 20358031 TI - A case of anaphylaxis after the ingestion of yacon. AB - Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55 year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots. PMID- 20358032 TI - The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes. AB - BACKGROUND: Hereditary gastrointestinal polyposis syndromes account for about 1% of all cases of colorectal cancer and are associated with a broad spectrum of extracolonic tumors. The early detection and accurate classification of these syndromes are essential, since effective methods for surveillance and treatment are available. METHODS: This review article is based on a selective literature search, the author's own work, and evidence-based guidelines and recommendations. RESULTS AND CONCLUSIONS: The diagnosis is initially suspected on the basis of the endoscopic findings and polyp histology. Because different syndromes can resemble each other phenotypically, e.g., autosomal dominant familial adenomatous polyposis and autosomal recessive MUTYH-associated polyposis, molecular genetic studies are important for differential diagnosis and for assessing the risk of recurrence. Identification of the familial mutation in an affected patient is a prerequisite for predictive testing in asymptomatic persons at risk and sometimes enables prognostication. In recent years, the rate of detection of mutations has risen by 10% to 30%, and clinically relevant genotype-phenotype correlations have been described for juvenile polyposis syndrome. Except in cases of mild adenomatous polyposis, phenotypic overlap among the hamartomatous polyposes often causes difficulties in differential diagnosis. Thus, in unclear cases, a pathologist with special expertise in gastrointestinal disorders should be consulted for the evaluation of polyp tissue. Aside from the monogenic polyposes, there are many other types of polyposis that are non-hereditary or of unknown cause, including the hyperplastic and mixed polyposis syndromes. Risk-adapted surveillance programs have been established for the more frequently occurring polyposes. PMID- 20358034 TI - Click synthesis of podand triazole-linked gold nanoparticles as highly selective and sensitive colorimetric probes for lead(II) ions. AB - Podand triazole-linked gold nanoparticles were designed via an in situ'click' reaction. The resulting gold nanoparticles were characterized by UV-vis spectroscopy, FT-IR spectroscopy, transmission electron microscopy (TEM). Podand triazole-linked gold nanoparticles were utilized as colorimetric probes for Pb(2+)via Pb(2+)-induced gold nanoparticle aggregation which incorporates two podand molecules from different nanoparticles forming an intermolecule type of association. Moreover, the application of the resulting gold nanoparticles to evaluate the exceeding standard of lead ions in drinking water and leaded paint was investigated. PMID- 20358035 TI - Observation of oscillatory behavior during the dissolution of a pharmaceutical compound and evidence for the existence of an inverse Ostwald rule. AB - Oscillatory kinetic behavior is reported for the first time in a solid-state phase transformation of an organic compound, specifically, in the dissolution of Form V crystals of etoricoxib in neat toluene. The dissolution involves kinetics of bistability due to the generation of a second polymorph, Form I, during the process. While an attempt is made to reconcile the periodic behavior with the oscillatory rate coefficient predicted by time-dependent Marcus theory, more successful simulations of the data are obtained using superimposed, elementary dispersive kinetic models for both dissolution and nucleation-and-growth. Contrastingly, the dissolution of Form V in toluene containing a suspected small quantity of methanol/base contaminant shows that the phase transformation of Form V to the less-stable Form I crystals is rate-limiting and that the process is well described by a single, elementary dispersive kinetic model (i.e., no oscillations are observed). The latter observation lends support to the bistability hypothesis and provides evidence for the existence of a 'corollary' to Ostwald's rule of stages. PMID- 20358033 TI - Chlamydial zoonoses. AB - BACKGROUND: Zoonoses were already a subject of intense interest even before the SARS and avian influenza epidemics arose. For many years, chlamydiae have been hypothesized to be important zoonotic pathogens, because of their wide distribution and their infectious cycle. This article provides an overview of the current state of knowledge on this subject. METHODS: The authors present a selective review of the literature as well as their own findings. RESULTS: The scientific knowledge of the distribution and infectious cycle of chlamydiae is still inadequate. The laboratory diagnosis of chlamydial zoonoses remains unsatisfactory in both human and veterinary medicine, as there are no commercially available sensitive and species-specific tests. Acute chlamydial infections are usually treated with macrolides, tetracyclines, or quinolones. Persistent varieties are not covered by standard therapy. CONCLUSIONS: There is a considerable need for research on chlamydial infections, especially with regard to the diagnosis and treatment of persistent varieties. PMID- 20358036 TI - Rydberg gas theory of a glow discharge plasma: II. Electrode kinetics (probe theory) and the thermal rate constant for Symmetrical charge transfer involving Rydberg atoms of Ar. AB - A steady state chemical kinetic model is developed to describe the conduction of electrical current between two probes, of relatively large surface area, immersed in a fast flowing plasma by the mechanism of charge transfer through a gas of Rydberg atoms. It correctly predicts the shape of current-voltage profiles which are similar to those of Langmuir, or floating double probe measurements. The difference is that the plateau current at the probe reflects the transport limited ion current at the cathodic electrode, even when the probe is being scanned in the anodic region. The sharp gradient leading up to the plateau of the I-V curve is associated with the field dependence of the efficiency of Rydberg atom ionisation, not the electron temperature. This approach gives a good qualitative explanation of experimental behaviour over a wide range of probe bias voltages and includes the occurrence of electron impact ionisation at the anode. It also gives a value for the thermal rate coefficient of symmetrical charge transfer between Rydberg atoms of Ar (8.2 x 10(-7) molecule(-1) cm(3) s(-1), at 313 K; plasma density approximately = 10(10) atoms cm(-3), total pressure = 2.7 mbar). PMID- 20358037 TI - Thermochemistry from ion-molecule reactions of hydrated ions in the gas phase: a new variant of nanocalorimetry reveals product energy partitioning. AB - A new variant of nanocalorimetry is proposed for the thermochemical analysis of ion-molecule reactions of hydrated ions in the gas phase. The average number of water molecules evaporating during the reaction is extracted by quantitative modeling of the average number of water molecules in the reactant and product cluster distribution as a function of time, taking into account black-body radiation induced dissociation. The method is tested on reactions of (H2O)n(-) with O2 and CO2, and the core exchange reaction of CO2(-)(H2O)n with O2 to yield O2(-)(H2O)n and CO2. Reproducible results are obtained for the number of water molecules evaporating. Nanocalorimetric analysis reveals a non-ergodic component of DelatE(ne) = 59 +/- 14 kJ mol(-1) in the core exchange reaction, most likely carried away by the neutral CO2 product. Extrapolation to solution phase values suggests hydration enthalpies of DeltaH(hyd) = -375 +/- 30 kJ mol(-1) for O2(-) and DeltaH(hyd) = -268 +/- 27 kJ mol(-1) for CO2(-). PMID- 20358038 TI - Effect of polymer, poly(ethylene glycol)(PEG-400), on solvent and rotational relaxation of coumarin-480 in an ionic liquid containing microemulsions. AB - The effect of a polymer, polyethylene glycol with a molecular weight of 400 (PEG 400), on the dynamics of solvent and rotational relaxation have been investigated in [bmim][BF4]/TX100/cyclohexane microemulsions using steady state and time resolved fluorescence spectroscopy as a tool and coumarin 480 (C-480) as a fluorescence probe. The size of the microemulsions increases with addition of PEG 400, which was revealed by dynamic light scattering (DLS) measurement. This leads to faster collective motion of the cations and anions of [bmim][BF4], which contributes to faster solvent relaxation in microemulsions. PMID- 20358039 TI - Direct ab initio MD study on the interaction of hydroperoxy radical (HOO) with water molecules. AB - Structures and electronic states of the HOO radical interacting with water molecules, expressed by HOO(H2O)n (n = 1 and 2), have been investigated by means of a direct ab initio molecular dynamics (MD) method. From the static ab initio calculation of HOO-H2O complex, two types of HOO radical were found: i.e., the HOO radical acts as a hydrogen donor or acceptor in the complex (n = 1). The binding energies of former and latter complexes were calculated to be 8.7 and 3.3 kcal mol(-1), respectively, at the QCISD/6-311++G(2d,2p) level. In the case of 1:2 complex HOO(H2O)2, a cyclic structure with a hydrogen donor of HOO was obtained as the stable form. Effects of zero point vibration on the structures and hyperfine coupling constants of the HOO radical were also investigated. The structures and electronic states of HOO(H2O)n (n = 1 and 2) were discussed on the basis of theoretical results. PMID- 20358040 TI - Combinatorial screening of a lanthanide complex library for luminescence sensing of amino acids. AB - A lanthanide complex library including 196 combinations of N-heteroaromatic ligands, luminescent lanthanide centers and amino acid substrates was prepared to develop visible and near-infrared luminescent sensory systems for a series of amino acids. PMID- 20358041 TI - Preparation and structures of enantiomeric dinuclear zirconium and hafnium complexes containing two homochiral N atoms, and their catalytic property for polymerization of rac-lactide. AB - The hydroxy- and phenoxy-bridged dinuclear zirconium and hafnium complexes and of an amine-pyridine-bis(phenolate) ligand (H(2)L) were prepared from the reaction of Na(2)L and ZrCl(4) in the presence of 0.5 equiv of water in THF, while the reaction of H(2)L with NaH and then with ZrCl(4) in the freshly distilled THF gave an eight-coordinate bis(homoleptic) mononuclear complex L(2)Zr (). Two homochiral N atoms were created in each complex upon coordination of the unsymmetric tertiary amine ligands to the metal centers. Enantiomeric dinuclear complexes and both undergo spontaneous resolution during crystallization. The molecular structure of each enantiomer of and , as well as the structure of , was determined by X-ray analysis and the circular dichroism spectra of N(R)N(R)- and N(S)N(S)- were studied. The racemates of and catalyzed controlled polymerization of rac-lactide in terms of the linearity of molecular weight versus conversion, forming isotactic-rich polylactide in high yields with a narrow polydispersity. PMID- 20358044 TI - Deep-space glycine formation via Strecker-type reactions activated by ice water dust mantles. A computational approach. AB - A Strecker-type synthesis of glycine by reacting NH(3), H(2)C=O and HCN in presence of ice water (H(2)O-ice) as a catalyst has been theoretically studied at B3LYP/6-31+G(d,p) level within a cluster approach in order to mimic reactions occurring in the interstellar and circumstellar medium (ICM). Results indicate that, despite the exoergonic character of the considered reactions occurring at the H(2)O-ice surface, the kinetics are slow due to relatively high electronic energy barriers (DeltaU(0)(?)=15-45 kcal mol(-1)). Reactions occurring within H(2)O-ice cavities, in which ice bulk effects have been modeled by assuming a dielectric continuum (epsilon=78), show energy barriers low enough to allow NH(2)CH(2)OH formation but not NH=CH2 (DeltaU(0)(?)= 2 and 21 kcal mol(-1), respectively) thus hindering the NH(2)CH(2)CN formation, i.e. the precursor of glycine, through Strecker channels. Moreover, hydrolysis of NH(2)CH(2)CN to give glycine is characterized by high electronic energy barriers (DeltaU(0)(?)=27-34 kcal mol(-1)) and cannot readily occur at cryogenic temperatures. Nevertheless, the facts that NH=CH(2) formation can readily be achieved through the radical radical HCN+2H - NH-->CH2 reaction [D. E. Woon, Astrophys. J., 2002, 571, L177 L180], and that present results indicate that the Strecker step of NH=CH(2)+HCN- >NH(2)CH(2)CN exhibits a relative low energy barrier (DeltaU(0)(?)=8-9 kcal mol( 1)), suggest that a combination of these two mechanisms allows for the formation of NH(2)CH(2)CN in the ICM. These results strengthen the thesis that NH(2)CH(2)CN could have been formed and protected by icy dust particles, and then delivered through micro-bombardments onto the early Earth, leading to glycine formation upon contact with the primordial ocean. PMID- 20358043 TI - Targeted proteomics for Chlamydomonas reinhardtii combined with rapid subcellular protein fractionation, metabolomics and metabolic flux analyses. AB - In the era of fast genome sequencing a critical goal is to develop genome-wide quantitative molecular approaches. Here, we present a metaproteogenomic strategy to integrate proteomics and metabolomics data for systems level analysis in the recently sequenced unicellular green algae Chlamydomonas reinhardtii. To achieve a representative proteome coverage we analysed different growth conditions with protein prefractionation and shotgun proteomics. For protein identification, different genome annotations as well as new gene model predictions with stringent peptide filter criteria were used. An overlapping proteome coverage of 25%, consistent for all databases, was determined. The data are stored in a public mass spectral reference database ProMEX (http://www.promexdb.org/home.shtml). A set of proteotypic peptides comprising Calvin cycle, photosynthetic apparatus, starch synthesis, glycolysis, TCA cycle, carbon concentrating mechanisms (CCM) and other pathways was selected from this database for targeted proteomics (Mass Western). Rapid subcellular fractionation in combination with targeted proteomics allowed for measuring subcellular protein concentrations in attomole per 1000 cells. From the same samples metabolite concentrations and metabolic fluxes by stable isotope incorporation were analyzed. Differences were found in the growth dependent crosstalk of chloroplastidic and mitochondrial metabolism. A Mass Western survey of all detectable carbonic anhydrases partially involved in carbon concentrating mechanism (CCM) revealed highest internal cell concentrations for a specific low-CO2-inducible mitochondrial CAH isoform. This indicates its role as one of the strongest CO2-responsive proteins in the crosstalk of air-adapted mixotrophic chloroplast and mitochondrial metabolism in Chlamydomonas reinhardtii. PMID- 20358042 TI - Cyclization of aromatic polyketides from bacteria and fungi. PMID- 20358045 TI - Modular glass chip system measuring the electric activity and adhesion of neuronal cells--application and drug testing with sodium valproic acid. AB - We developed a modular neurochip system by combining a small (16x16 mm2) glass neurochip (GNC) with a homemade head stage and commercial data acquisition hardware and software. The system is designed for the detection of the electric activity of cultivated nerve or muscle cells by a 52-microelectrode array (MEA). In parallel, cell adhesion can be registered from the electric impedance of an interdigitated electrode structure (IDES). The GNC was tested with various cell lines and primary cells. It is fully autoclavable and re-useable. Murine embryonic primary cells were used as a model system to correlate the electric activity and adhesion of neuronal networks in a drug test with sodium valproic acid. The test showed the advantage of the parallel IDES and MEA measurements, i.e. the parallel detection of cytotoxic and neurotoxic effects. Toxic exposure of the cells during neuronal network formation allows for the characterization of developmental neurotoxic effects even at drug concentrations below the EC50-value for acute neurotoxic effects. At high drug concentrations, the degree of cytotoxic damage can still be assessed from the IDES data in the event that no electric activity develops. The GNC provides optimal cell culture conditions for up to months in combination with full microscopic observability. The 4'' glass wafer technology allows for a high precision of the GNC structures and an economic production of our new system that can be applied in general and developmental toxicity tests as well as in the search for neuro-active compounds. PMID- 20358046 TI - Copper(II)-catalyzed highly diastereoselective three-component reactions of aryl diazoacetates with alcohols and chalcones: an easy access to furan derivatives. AB - Copper(II) complexes are efficient catalysts in three-component reactions of aryl diazoacetates with alcohols and chalcones to give gamma-hydroxyketone derivatives in high yield with excellent diastereoselectivity. The resulting coupling adducts can be easily converted into furan-containing oligoaryls, tetrahydrofuran and 2,3 dihydrofuran derivatives. PMID- 20358047 TI - Asymmetric synthesis of 2-arylpyrrolidines starting from gamma-chloro N-(tert butanesulfinyl)ketimines. AB - The enantioselective reductive cyclization of gamma-chloro N-(tert butanesulfinyl)ketimines towards the short and efficient synthesis of (S)- and (R)-2-arylpyrrolidines (ee >99%) is described for the first time by treatment with LiBEt(3)H and subsequent acid deprotection. PMID- 20358048 TI - Dendrimers and nanotubes: a fruitful association. AB - Dendrimers and nanotubes (particularly carbon nanotubes (CNTs)) are two types of nano-objects which have met independently a large success within the scientific community. Surprisingly, their association has been poorly studied up to now, despite some original properties recently reported and that will be emphasized in this tutorial review. One can name as a few, the elaboration of single-walled carbon nanotubes from dendrimers, CNTs functionalised with dendrimers displaying field effect transistor properties and/or used as biosensors, and modified biological properties (either enhanced biocompatibility or enhanced antimicrobial activity). However, not all the nanotubes are carbon nanotubes, and original properties were also reported for dendrimers associated with non-CNTs, such as the elaboration of specific nano-filters and of highly efficient and reusable catalysts. Furthermore, non-CNTs constituted of dendrimers, particularly those obtained by layer-by-layer deposition of positively and negatively charged dendrimers associated with quantum dots display an excellent detection limit for DNA hybridization (10 fM). PMID- 20358049 TI - Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. AB - Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors. A recently discovered thyroid hormone derivative, 3-iodothyronamine (T(1)AM), has distinct biological effects that are opposite those of thyroid hormone. Here we investigate the effects of T(1)AM on thyroid hormone transporters using COS-1 cells transfected with the multispecific organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 1C1, as well as the specific thyroid hormone transporters MCT8 and MCT10, and show that T(1)AM displays differential inhibition of T(3) and T(4) cellular uptake by these transporters. T(1)AM inhibits T(3) and T(4) transport by OATP1A2 with IC(50) values of 0.27 and 2.1 microM, respectively. T(4) transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T(1)AM with an IC(50) of 4.8 microM. T(1)AM also inhibits both T(3) and T(4) uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC(50) values of 95 and 31 microM, respectively. By contrast, T(1)AM has no effect on thyroid hormone transport by OATP1B3 and MCT10. Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T(1)AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system. PMID- 20358050 TI - Validation of a blood plasma separation system by biomarker detection. AB - A microfluidic system was developed for blood plasma separation at high flow rate. This system uses only hydrodynamic forces to separate plasma from whole blood. The microfluidic network features a series of constrictions and bifurcations to enhance the product yield and purity. A maximum purity efficiency of 100% is obtained on blood with entrance hematocrit level up to 30% with a flow rate of 2 mL h(-1). Flow cytometry was performed on the extracted plasma to evaluate the separation efficiency and to assess cell damage. A core target of this study was the detection of cell-free DNA from the on-chip extracted plasma. To this effect, PCR was successfully carried out off-chip on the cell-free DNA present in the plasma extracted on-chip. A house-keeping gene sequence (GAPDH) was amplified without the need for a purification after the separation, thereby showing the high quality of the plasma sample. The resulting data suggests that the system can be used as a preliminary module of a total analysis system for cell-free DNA detection in human plasma. PMID- 20358051 TI - Single-molecule sequence detection via microfluidic planar extensional flow at a stagnation point. AB - We demonstrate the use of a microfluidic stagnation point flow to trap and extend single molecules of double-stranded (ds) genomic DNA for detection of target sequences along the DNA backbone. Mutant EcoRI-based fluorescent markers are bound sequence-specifically to fluorescently labeled ds lambda-DNA. The marker DNA complexes are introduced into a microfluidic cross slot consisting of flow channels that intersect at ninety degrees. Buffered solution containing the marker-DNA complexes flows in one channel of the cross slot, pure buffer flows in the opposing channel at the same flow rate, and fluid exits the two channels at ninety degrees from the inlet channels. This creates a stagnation point at the center of a planar extensional flow, where marker-DNA complexes may be trapped and elongated along the outflow axis. The degree of elongation can be controlled using the flow strength (i.e., a non-dimensional flow rate) in the device. Both the DNA backbone and the markers bound along the stretched DNA are observed directly using fluorescence microscopy, and the location of the markers along the DNA backbone is measured. We find that our method permits detection of each of the five expected target site positions to within 1.5 kb with standard deviations of <1.5 kb. We compare the method's precision and accuracy at molecular extensions of 68% and 88% of the contour length to binding distributions from similar data obtained via molecular combing. We also provide evidence that increased mixing of the sample during binding of the marker to the DNA improves binding to internal target sequences of dsDNA, presumably by extending the DNA and making the internal binding sites more accessible. PMID- 20358052 TI - Methodology for collecting, storing, and analyzing human milk for volatile organic compounds. AB - Biomonitoring, or the measurement of environmental chemicals in human tissues and fluids, is used to supplement-and in some cases replace-more traditional exposure assessments which measure chemicals in environmental media. Volatile organic compounds (VOCs) in physiological fluids are biomarkers of exposure that present numerous challenges for sample collection and analysis. To date, a thorough evaluation of methods for collection and analysis of breast milk samples for volatiles has not been conducted. In this paper, we describe the development and validation of methods for collecting, storing, and analyzing 36 volatile organic compounds (VOCs) in breast milk to assess VOC exposure of lactating women and nursing infants. Volatile analyte loss was minimized by collecting and storing samples in containers with small headspace volume resulting in recovery >or=70% for all 10 VOCs detected in most breast milk samples. Potential contamination by chloroform, benzene, toluene, ethylbenzene, xylenes, and methyl-tert-butyl ether was minimized by using specially treated sample collection materials. Method detection limits in the low parts per trillion range were achieved by using solid phase microextraction headspace sampling, gas chromatography, and selective ion monitoring mass spectrometry. We used this method to analyze 3 mL aliquots of breast milk collected from 12 women and found that 10 of the 36 VOCs were detectable in most samples (median values follow): m/p-xylene, 0.539 ng mL(-1); toluene, 0.464 ng mL(-1); 1,4-dichlorobenzene, 0.170 ng mL(-1); tetrachloroethylene, 0.165 ng mL(-1); o-xylene, 0.159 ng mL(-1); ethylbenzene, 0.0149 ng mL(-1); styrene, 0.129 ng mL(-1); benzene, 0.080 ng mL(-1); chloroform, 0.030 ng mL(-1); and methyl-tert-butyl ether, 0.016 ng mL(-1). PMID- 20358054 TI - Synthesis of [RhCl(CO)(cyclopentadienone)]2 from [RhCl(cod)]2 and a 1,6-diyne under CO: application to Rh(I)-catalyzed tandem [2+2+1] carbonylative cycloaddition of diynes and Claisen rearrangement. AB - Although Rh(I)Cl(CO)(cpd) (cpd = cyclopentadienone) complexes were identified more than 40 years ago, their exact structures have not been determined because of the polymeric nature of these complexes. We determined the structure of [Rh(I)Cl(CO)(cpd)](2), which was formed by the reaction of [Rh(cod)Cl](2) with a 1,6-diyne under CO. In addition, based on determination of the structure of the [Rh(I)Cl(CO)(cpd)](2) complex, we identified a new catalytic tandem reaction--the Rh-catalyzed [2+2+1] carbonylative cycloaddition of phenoxide-substituted diynes and Claisen rearrangement. PMID- 20358053 TI - The sodium/galactose symporter crystal structure is a dynamic, not so occluded state. AB - The recent elucidation of the sodium/galactose symporter structure from the Vibrio parahaemolyticus bacterium, vSGLT, has revealed a similarity in the core architecture with transporters from different gene families, including the leucine transporter (LeuT). Even though several transporters sharing this core have been structurally determined over the past few years, vSGLT is the only one crystallized in the substrate-bound inward-facing conformation so far. In this study, we report the first insight into the dynamics and coordination of the galactose (Gal) and proposed Na+ ion in vSGLT using a series of molecular dynamics simulations with a total time of about 0.1 micros. Our study reveals new residues, not observed in the crystal structure, which closely interact with the Na(+) ion or the substrate for extended times, and shows that in the crystallized conformation, a Na+ ion placed at the site equivalent to Na2 in LeuT can escape into the intracellular (IC) space in the absence of external forces. We have identified the highly conserved Asp189 as a likely binding residue on the pathway of Na(+) into the IC cavity. The release of Gal, on the other hand, requires the rotation of the side chain of the inner hydrophobic gate, Tyr263, without a significant change in vSGLT backbone conformation. Our simulations further show that the crystal structure represents but one accessible binding pose of Gal and Na+ among an ensemble of microstates, and that the Gal undergoes versatile alternate interactions at the binding pocket. PMID- 20358055 TI - Magnetism in metal-organic capsules. AB - Nickel and cobalt seamed metal-organic capsules have been isolated and studied using structural, magnetic and computational approaches. Antiferromagnetic exchange in the Ni capsule results from coordination environments enforced by the capsule framework. PMID- 20358060 TI - Monitoring electronic structure changes of TiO2(110) via sign reversal of adsorbate vibrational bands. AB - The adsorption of NO on single crystalline rutile TiO(2)(110) surfaces at 100 K and the subsequent formation of N(2)O via NO dimer intermediates was studied by reflection-absorption infrared spectroscopy using a UHV-FTIR system. Analysis of the IR data reveals that the occurrence of s-polarized adsorbate vibrational bands always increases the reflectivity, giving negative bands, whereas p polarized bands are either positive or negative, depending on the reduction state of the substrate. This sign reversal of optical bands is caused by vacancy doping, which also affects the optical constants governing the complex interplay between reflection and transmission of p-polarized light on a dielectric substrate. PMID- 20358056 TI - Sensitive electrochemical immunosensor for matrix metalloproteinase-3 based on single-wall carbon nanotubes. AB - A novel electrochemical immunosensor for the detection of matrix metalloproteinase-3 (MMP-3), a cancer biomarker protein, based on vertically aligned single-wall carbon nanotube (SWCNT) arrays is presented. Detection was based on a sandwich immunoassay consisting of horseradish peroxidase (14-16 labels) conjugated to a secondary antibody and/or a polymer bead loaded with multi-enzyme labels. Performance was optimized by effective minimization of non specific binding (NSB) events using Bovine serum albumin (BSA), Tween-20 and optimization of the primary antibody and secondary antibody concentrations. Results provided a detection limit of 0.4 ng mL(-1) (7.7 pM) for the 14-16 label sensor protocol and 4 pg mL(-1) (77 fM) using a multiply enzyme labeled polymeric bead amplification strategy in 10 microL of calf serum. This immunosensor based on SWCNT arrays offers great promise for a rapid, simple, cost-effective method for clinical screening of cancer biomarkers for point-of-care diagnosis. PMID- 20358061 TI - Direct measurement of vertical binding energy of a hydrated electron. AB - We present the first measurement of the vertical binding energy (VBE) of a hydrated electron in bulk water by the time-resolved photoelectron spectroscopy (TRPES) of the charge-transfer-to-solvent (CTTS) reaction in aqueous NaI solution. Our best estimate of VBE is 3.27 +/- 0.10 eV for H(2)O and 3.20 +/- 0.10 eV for D(2)O. PMID- 20358062 TI - Patterns in the Belousov-Zhabotinsky reaction in water-in-oil microemulsion induced by a temperature gradient. AB - We investigate the effect of changing temperature in the ferroin-catalysed Belousov-Zhabotinsky (BZ) reaction dispersed in the water nanodroplets of a water in-oil aerosol OT (AOT) microemulsion, which undergoes a temperature-induced percolation transition at about 38 degrees C. We observe stationary Turing patterns at temperatures in the range 15-35 degrees C and bulk oscillations at T = 40-55 degrees C. When a temperature gradient DeltaT is applied normal to a thin layer of the BZ-AOT reaction mixture, the range of patterns observed is dramatically expanded. Anti-phase oscillatory Turing patterns, leaping waves, and chaotic waves emerge, depending on the temperature gradient and the average temperature. These new patterns originate from the coupling between a low temperature Turing mode and a high temperature Hopf mode. Simulations with a simple model of the BZ-AOT system give good agreement with our experimental results. PMID- 20358063 TI - Low temperature rate coefficients for reactions of the butadiynyl radical, C4H, with various hydrocarbons. Part I: reactions with alkanes (CH4, C2H6, C3H8, C4H10). AB - The kinetics of the reactions of the linear butadiynyl radical, C4H (CCCCH), with methane, ethane, propane and butane have been studied over the temperature range of 39-300 K using a CRESU (Cinetique de Reaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. The rate coefficients, except for the reaction with methane, show a negative temperature dependence and can be fitted with the following expressions over the temperature range of this study: k(C2H6) = 0.289 x 10(-10) (T/298 K)(-1.23) exp(-24.8 K/T) cm3 molecule(-1) s(-1); k(C3H8) = 1.06 x 10(-10) (T/298 K)(-1.36) exp(-56.9 K/T) cm3 molecule(-1) s(-1); k(C4H10) = 2.93 x 10(-10) (T/298 K)(-1.30) exp(-90.1 K/T) cm3 molecule(-1) s(-1). The rate coefficients for the reaction with methane were measured only at 200 K and 300 K yielding a positive temperature dependence: k(CH4) = 1.63 x 10(-11) exp(-610 K/T) cm3 molecule(-1) s(-1). Possible reaction mechanisms and product channels are discussed in detail for each of these reactions. Potential implications of these results for models of low temperature chemical environments, in particular cold interstellar clouds and planetary atmospheres such as that of Titan, are considered. PMID- 20358064 TI - Low temperature rate coefficients for reactions of the butadiynyl radical, C4H, with various hydrocarbons. Part II: reactions with alkenes (ethylene, propene, 1 butene), dienes (allene, 1,3-butadiene) and alkynes (acetylene, propyne and 1 butyne). AB - The kinetics of the reactions of the linear butadiynyl radical, C4H (CCCCH), with a variety of unsaturated hydrocarbons have been studied over the temperature range of 39-300 K using a CRESU (Cinetique de Reaction en Ecoulement Supersonique Uniforme, or reaction kinetics in uniform supersonic flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. The rate coefficients for all the reactions studied are found to all be in excess of 10( 10) cm(3) molecule(-1) s(-1) over the entire temperature range. They can be fitted with the following expressions (valid from 39 K to 300 K, with RMS deviations of the experimental points from the predicted values shown, to which should be added 10% possible systematic error) for reaction of C4H with alkenes: k(C2H4) = (1.95 +/- 0.17) x 10(-10) (T/298 K)(-0.40) exp(9.4 K/T) cm3 molecule( 1) s(-1); k(C3H6) = (3.25 +/- 0.12) x 10(-10) (T/298 K)(-0.84) exp(-48.9 K/T) cm3 molecule(-1) s(-1); k(1-C4H8) = (6.30 +/- 0.35) x 10(-10) (T/298 K)(-0.61) exp( 65.0 K/T) cm3 molecule(-1) s(-1), for reaction of C4H with dienes: k(C3H4) = (3.70 +/- 0.34) x 10(-10) (T/298 K)(-1.18) exp(-91.1 K/T) cm3 molecule(-1) s(-1); k(1,3-C4H6) = (5.37 +/- 0.30) x 10(-10) (T/298 K)(-1.25) exp(-116.8 K/T) cm3 molecule(-1) s(-1), and for reaction of C4H with alkynes: k(C2H2) = (1.82 +/- 0.19) x 10(-10) (T/298 K)(-1.06) exp(-65.9 K/T) cm3 molecule(-1) s(-1); k(C3H4) = (3.20 +/- 0.08) x 10(-10) (T/298 K)(-0.82) exp(-47.5 K/T) cm3 molecule(-1) s(-1); k(1-C4H6) = (3.48 +/- 0.14) x 10(-10) (T/298 K)(-0.65) exp(-58.4 K/T) cm3 molecule(-1) s(-1). Possible reaction mechanisms and product channels are discussed in detail for each of these reactions. Potential implications of these results for models of low temperature chemical environments, in particular cold interstellar clouds and star-forming regions, are considered. PMID- 20358065 TI - Theoretical study on conformational preferences of ribose in 2-thiouridine--the role of the 2'OH group. AB - Conformational changes in ribose are well-known to play a significant role in biomolecular identification. The mechanism of selectivity towards C3'-endo conformation (conformer b) in ribose of 2-thiouridine has been studied using DFT (B3LYP) and MP2 methodology, together with 6-31+G(d,p) basis set. The polarity of the C2S2 bond is enhanced due to the orientation of H2' towards the S2 atoms, which leads to a difference in the corresponding bond lengths, the atomic charges and the vO2'H2' stretch vibrations in all the conformers. NBO analysis shows that charge transfer mainly occurs in the C2N3 and C2S2 orbitals. The higher stability of conformer b is attributed to its larger orbital interaction energies within the 2-thiouracil base, and total orbital interaction energies of conformer b. Our conclusion is that the distant electrostatic rather than hydrogen bonding effects between 2'OH and the S2 atoms play the dominant role in the orbital interaction, and enhance the selectivity towards the C3'-endo conformation of ribose. PMID- 20358066 TI - Rydberg gas theory of a glow discharge plasma: I. Application to the electrical behaviour of a fast flowing glow discharge plasma. AB - Current-voltage (I-V) curves have been measured, independent of the main discharge, for electricity passing through the steady state fast flowing 'afterglow' plasma of a low power dc glow discharge in Ar. Voltage profiles along the axial line of conduction have been mapped using fixed probes and potentiometry, and the mass spectra of cations emerging from the downstream sampling Cone, also acting as a probe anode, were recorded simultaneously. Floating double probe experiments were also carried out. The electrical behavior is consistent with the well established I-V characteristics of such discharges, but does not comply with classical plasma theory predictions. The plasma decays along the line of conduction, with a lifetime of approximately 1 ms, despite carrying a steady state current, and its potential is below that of the large surface area anode voltage; a situation which cannot exist in the presence of a conventional free ion-electron plasma, unless the electron temperature is super cold. Currents, large by comparison with the main discharge current, and independent of it, are induced to flow through the downstream plasma, from the Anode (acting as a cathode) to the anodic ion exit Cone, induced by electron impact ionisation at the anode, but without necessarily increasing the plasma density. It appears to be conducted by direct charge transfer between a part of the anode surface (acting as cathode to the auxiliary circuit) and the plasma, without secondary electron emission or heating, which suggests the direct involvement of Rydberg atom intermediates. The reaction energy defect (= the work function of the electrode surface) fits with the plasma potential threshold observed for the cathodic reaction to occur. A true free ion-electron plasma is readily detected by the observation of cations at the anode surface, when induced at the downstream anode, at high bias voltages, by the electron impact ionisation in the boundary region. In contrast to the classical model, the complex electrical (and mass spectrometric) behaviour fits qualitatively, but can be understood well, with the Rydberg gas model described in papers II and III (R. S. Mason, and R. S. Mason and P. Douglas, PCCP, 2010, DOI: 10.1039/b918081h and b918083d) over a wide range of probe bias voltages. The full cycle of behavior is then described for the development of a true secondary discharge within the downstream plasma. PMID- 20358067 TI - Rydberg gas theory of a glow discharge plasma: III. Formation, occupied state distributions, free energy, and kinetic control. AB - It has been suggested that Rydberg gas atoms are involved in conducting electricity through a steady state flowing afterglow (FAG) discharge plasma (R. S. Mason, D. J. Mitchell and P. M. Dickinson, Phys. Chem. Chem. Phys., 2010, DOI: ). From known properties of Rydberg atoms, a statistical model is developed here to find the distribution of levels (principal quantum number n) occupied in such a hypothetical Rydberg gas. It behaves non-ideally at positive column plasma densities, predicting 30 < n < 150, peaking at n approximately = 85. These values depend on assumptions concerning the power of n dependency of 'pressure ionization' and the free charge density. The occupied states are very long-lived and almost completely separated from the low n states by the low probability of intermediate levels. The effects of Rydberg gas (N(R)) and free charge densities are examined. The gas can exist in a deep free energy well (> 120 kJ mol(-1) below ionisation level when 10(10) < or = N(R) < or = 10(11) atoms cm(-3)) but this is approximately 11 kJ mol(-1) higher than that of the equivalent free ion electron gas; therefore if it exists in preference to the classical form of the plasma, it is controlled by kinetic factors. A mechanism is suggested by which this could occur. Thus, whilst ionization by high energy electron impact occurs at the Cathode Fall-Negative Glow (NG) boundary as usual, excitation of Rydberg atoms becomes more probable, by electrons slowed by collision and deceleration at the opposite NG-Positive Column (PC) plasma boundary. The atoms become stabilized after passing into the PC, by collisionally induced (nlm) mixing of states and the removal of free charge by charge transfer (and hence the passage of electric current through the Rydberg gas). The coupling of Rydberg states with the ionization continuum is poor; therefore, if the rate of their charge transfer is greater than that of their ionization, the Rydberg gas will remain relatively charge free and hence stable when it is conducting a current. When applied to the FAG plasma, the model provides a self-consistent interpretive framework for all its electrical, mass spectrometric and chemical behaviour. The effect on the optical spectroscopy of these plasmas is considered briefly. PMID- 20358068 TI - Interplay of stereo-electronic, environmental, and dynamical effects in determining the EPR parameters of aromatic spin-probes: INDCO as a test case. AB - An integrated computational strategy for the evaluation of reliable structures and magnetic properties of spin probes and spin labels has been extended to aromatic species. From an electronic point of view, delocalization of the unpaired electron density over aromatic moieties reduces significantly the computed nitrogen isotropic hyperfine coupling constant (A(N)) with respect to values characteristic of aliphatic nitroxides. Solvent effects in not too high polarity media are quite small, but not negligible. At this stage computed A(N) are lower than their experimental counterparts by more than 1 G. Inclusion of vibrational averaging effects by molecular dynamics simulations with a new reliable force field restores full agreement with experiment pointing out the limits of static approaches irrespective of the sophistication of the electronic quantum mechanical method. The generality and computational effectiveness of the proposed integrated approach paves the route toward a reliable analysis of the interplay of stereo-electronic, environmental, and dynamical effects in tuning the properties of large flexible magnetic systems of biological and technological interest. PMID- 20358069 TI - Electromagnetic field enhancement in the gap between two Au nanoparticles: the size of hot site probed by surface-enhanced Raman scattering. AB - We have estimated the apparent size of the 'hot' site for surface-enhanced Raman scattering (SERS) located within the gap between two spherical Au nanoparticles. Initially, 55-nm sized Au nanoparticles are laid on a thiol-group terminated silane film, and then 1,4-phenylenediisocyanide (1,4-PDI) molecules are self assembled onto the Au nanoparticles. 1,4-PDI is bonded to Au by forming one Au-CN bond, with another isocyanide group being pendent with respect to the Au surface. Up to this point, no Raman scattering is detected at all for 1,4-PDI. Upon attaching new Au nanoparticles onto the pendent isocyanide groups of 1,4-PDI, a Raman signal is distinctly observed. In agreement with the finite-difference time domain (FDTD) calculation, this is understood in terms of the electromagnetic hot sites formed at the gaps between two Au nanoparticles. The Raman signal does not increase further, however, even after the adsorption of additional 1,4-PDI onto the vacant surfaces of the second Au nanoparticles. To a rough estimate, about 400 molecules residing only within a 10-nm diameter area of the center of the gap, adsorbed in the first stage, are then conjectured to have contributed most of the measured Raman signal of 1,4-PDI. This apparently indicates that the size of 'hot' site is very limited. PMID- 20358070 TI - The first passage probability of intracellular particle trafficking. AB - The first passage probability (FPP), of trafficked intracellular particles reaching a displacement L, in a given time t or inverse velocity S = t/L, can be calculated robustly from measured particle tracks. The FPP gives a measure of particle movement in which different types of motion, e.g. diffusion, ballistic motion, and transient run-rest motion, can readily be distinguished in a single graph, and compared with mathematical models. The FPP is attractive in that it offers a means of reducing the data in the measured tracks, without making assumptions about the mechanism of motion. For example, it does not employ smoothing, segmentation or arbitrary thresholds to discriminate between different types of motion in a particle track. In contrast to conventional mean square displacement analysis, FPP is sensitive to a small population of trafficked particles that move long distances (> or = 5 microm), which are thought to be crucial for efficient long range signaling in theories of network dynamics. Taking experimental data from tracked endocytic vesicles, and calculating the FPP, we see how molecular treatments affect the trafficking. We show the FPP can quantify complicated movement which is neither completely random nor completely deterministic, making it highly applicable to trafficked particles in cell biology. PMID- 20358071 TI - Cycle formation from acetylene addition on C4H3 radicals. AB - Various reactions following acetylene addition on i- and n-C(4)H(3) radicals are studied using a modified G3B3 method. For the addition of C(2)H(2) on n-C(4)H(3), the commonly admitted phenyl radical decomposition path of Madden and coworkers has been considered. In addition, several energetically competitive cyclisation steps are described for the first time. Data concerning addition to form non cyclisable compounds are also provided. Addition on i-C(4)H(3) is extensively described including new cyclisation steps and hydrogen elimination reactions. The lowest energy path from n- or i-C(4)H(3) to a cyclic system goes through dehydro fulvene radicals formation, which in the case of n-C(4)H(3) + C(2)H(2) is energetically competitive to the formation of the phenyl radical. Considering the degradation of the latter, the formation of 6-dehydrofulvene is energetically competitive as compared to the decomposition to ortho-benzyne + H, which is the assumed main degradation channel of the phenyl radical. Rate constants for all the steps considered in this work are obtained through the conventional transition state theory and provided at the end of the paper. PMID- 20358072 TI - Second-order optical nonlinearity and ionic conductivity of nanocrystalline GeS2 Ga2S3-LiI glass-ceramics with improved thermo-mechanical properties. AB - IR-transparent chalcogenide glass-ceramics were fabricated through a careful ceramization process of the as-prepared 65 GeS(2) x 25 Ga(2)S(3) x 10 LiI glasses at a temperature of 403 degrees C for various durations. Owing to the precipitation of Li(x)Ga(y)S(z) crystals with a Ga(2)S(3)-like structure, clear second-harmonic generation was observed in the sample crystallized at 403 degrees C for 60 h, which has a greatly improved resistance to environmental impairment. Additionally, it is found that the shorter crystallization process (< or = 60 h) contributed to the enhancement of Li(+) ionic conductivity, whereas a longer heat treatment (80 h) would impair that of the glass-ceramics. The micro-structural origin of these varied properties was elucidated in detail. The corresponding results will be of benefit for the optimization of designed transparent chalcogenide glass-ceramics with improved thermo-mechanical properties, a permanent second-order optical nonlinearity, or a well-enhanced ionic conductivity for application in amorphous solid electrolytes. PMID- 20358073 TI - Driving force of metallo (Mg-H and Mg-Cl)-ene reaction mechanisms. AB - The potential-energy surfaces of the metallo-ene reactions of allyl-MgH and allyl MgCl with ethylene were studied using ab initio molecular-orbital (MO) methods. The concerted path and the stepwise path of the metallo-ene reactions of allyl MgH and allyl-MgCl with ethylene were identified and it was determined that the energy barriers on concerted paths of the metallo-ene reactions of allyl-MgH and allyl-MgCl with ethylene are lower than those on the stepwise paths. Furthermore, the concerted path of the metallo-ene reaction of allyl-MgCl with ethylene is more favorable than that of the allyl-MgH reaction system. The reaction mechanisms were analyzed using a CiLC method on the basis of CASSCF MOs. The driving force for the concerted path reactions arises from the migration process of the metal. The difference between the reactivity of allyl-MgH and allyl-MgCl can be explained with the reaction mechanism on the basis of the driving force. PMID- 20358074 TI - Durability of Pt/graphitized carbon catalysts for the oxygen reduction reaction prepared by the nanocapsule method. AB - Monodisperse Pt nanoparticles supported on a graphitized carbon black (GC; 150 m(2) g(-1)), which exhibits higher resistance to carbon corrosion than a conventional high-surface-area carbon black (CB; 800 m(2) g(-1)), were prepared by the nanocapsule method. Three kinds of 50 wt%-Pt loaded catalysts (our nanocapsule Pt/GC, a commercial Pt/GC, and a commercial Pt/CB) were subjected to the durability test by a standard potential step protocol (E = 0.9 V <--> 1.3 V vs. RHE, holding 30 s at each E, 1 min for one cycle) in N(2)-saturated 0.1 M HClO(4) solution at 25 degrees C. The oxygen reduction reaction (ORR) activities at these catalysts were evaluated from the hydrodynamic voltammograms in O(2) saturated 0.1 M HClO(4) solution at 25 degrees C by the rotating ring-disk electrode technique. The kinetically-controlled mass activities (MA) for the ORR at these catalysts at E = 0.85 to 0.70 V vs. RHE were found to decrease in proportion to log [number of potential step cycles] from 100 to 5000 cycles. It was found that our nanpcapsule Pt/GC showed the highest durability; the time elapsed for the reduction of MA(0.8V) to 700 A g(-1) (ca. 1/2 of the initial MA(0.8V)) at our Pt/GC was 30 and 60 times longer than those for the commercial Pt/GC and Pt/CB, respectively. It was found that the most important factor leading to both high MA and high durability is highly dispersed state of Pt nanoparticles with uniform size over the whole surface of the corrosion-resistant GC support, to which our nanocapsule method has contributed greatly. PMID- 20358075 TI - Structural changes in surface and bulk LiNi0.5Mn0.5O2 during electrochemical reaction on epitaxial thin-film electrodes characterized by in situ X-ray scattering. AB - Surface and bulk structural changes of LiNi(0.5)Mn(0.5)O(2) were investigated during electrochemical reaction using synchrotron X-ray scattering and a restricted reaction plane consisting of two-dimensional epitaxial-film electrodes. The changes in bulk structure confirmed lithium diffusion through the (110) surface, which was perpendicular to the two-dimensional (2D) edges of the layered structure. No (de)intercalation reaction was observed through the (003) surface at voltages of 3.0-5.0 V. However, intercalation did proceed through the (003) plane below 3.0 V, indicating unusual three-dimensional (3D) lithium diffusion in the over-lithiated 2D structure. During the electrochemical process, the surface of the electrode showed different structure changes from those of the bulk structure. The reaction mechanism of the intercalation electrodes for lithium batteries is discussed on the basis of surface and bulk structural changes. PMID- 20358076 TI - A structural and spectroscopic investigation of the hydrochlorination of 4,4' methylenedianiline. AB - The hydrochlorination of 4,4'-methylenedianiline, NH(2)C(6)H(4)CH(2)C(6)H(4)NH(2) (MDA), in chlorobenzene to produce 4,4'-methylenedianiline dihydrochloride, [H(3)NC(6)H(4)CH(2)C(6)H(4)NH(3)]Cl(2) (MDA x 2 HCl) is an important reaction for the production of isocyanates, which are used to manufacture polyurethanes. This reaction is examined here. MDA is moderately soluble in chlorobenzene, whereas MDA x 2 HCl is effectively insoluble. Controlled addition of anhydrous HCl to MDA in chlorobenzene led to the isolation of a solid whose stoichiometry is MDA x HCl. Crystals obtained from solutions of MDA x HCl in methanol were found by X ray analysis to consist of the basic hydrochloride salt, [MDAH(2)][Cl](2)[MDA](2)H(2)O, which is stabilised by complex hydrogen-bonding. The starting material MDA has an H-bonded structure in which the molecules are linked in a one-dimensional chain. Hydrogen-bonding is extensive in MDA x 2 HCl which contains ladders of [H(3)NC(6)H(4)CH(2)C(6)H(4)NH(3)](2+) dications stabilised by N-H...Cl linkages. Energy calculations on the crystalline systems allow an identification of the main factors in intermolecular cohesion; these are related to melting temperature and solubility data. Such improvements in understanding of solute-solute interactions are prerequisites for improving the atom economy of this important stage within the polyurethane manufacture process chain. The solid phase IR spectrum of MDA x 2 HCl is diagnostic, principally as a result of a Fermi resonance process. PMID- 20358077 TI - Structure and gelation mechanism of silk hydrogels. AB - Silk fibroin was regenerated from cocoons produced by the silkworm Bombyx Mori. Light scattering showed that an aqueous solution of the regenerated silk fibroin (RSF) was made of individual proteins with a weight average molar mass of about 4 x 10(5) g mol(-1) and a hydrodynamic radius of about 10 nm. Gel formation of RSF in acidic solutions was investigated as a function of the pH (2-4), concentration (0.5-10 g L(-1)) and temperature (5-70 degrees C). The structure of the gels was studied using light scattering and confocal laser scanning microscopy. The structure was found to be self-similar from length scales of less than 15 nm up to length scales of about 1 microm, and characterized by a correlation length of a few microns. Gel formation was tracked using turbidity, rheology, light scattering and circular dichroism. Gelation involves the formation of self similar aggregates with a growth rate that increases exponentially. The protein aggregation is correlated to, and perhaps caused by, the formation of beta sheets, the fraction of which also increases exponentially with time. PMID- 20358078 TI - Acetylenic spacers in phenylene end-substituted oligothiophene core for highly air-stable organic field-effect transistors. AB - Two thiophene-phenylene semiconductors, bis(2-phenylethynyl) end-substituted oligothiophenes (diPhAc-nTs, n = 2, 3), were synthesized and studied with respect to their optical, electrochemical, structural and electrical properties. The optical and electrochemical properties of the oligomers in solution were investigated by UV-vis absorption and photoluminescence spectroscopies, and cyclic voltammetry. High vacuum evaporated thin films were investigated by optical absorption, X-ray diffraction and AFM, and implemented as p-type semiconducting layers into organic thin-film transistors (OTFTs). A comparative study in solution and in the solid state with distyryl-oligothiophenes (DSnTs, n = 2, 3) reveals the great influence of acetylenic (-C[triple bond]C-) vs. olefinic (-C=C-) spacers in thiophene-phenylene derivatives on electronic structure, physical properties, and device efficiencies. Substituting olefinic for acetylenic pi-spacers in terthiophene-based conjugated semiconductors leads to one of incontrovertible attributes of OTFTs for low cost applications, a high mobility at low substrate temperature (T(sub)) i.e. typically 25 degrees C. Fine tuning in the HOMO/LUMO levels by reducing the HOMO level introduces increased air-oxidation strength of thin films where OTFTs provide exactly the same hole mobility value after 100 days in air. All the results suggested that introduction of carbon-carbon triple bonds provided an efficient route to highly air-stable organic thin film transistors. PMID- 20358079 TI - Controlling particle morphology and size in the synthesis of mesoporous SBA-15 materials. AB - Plate-like particles of SBA-15 form from smaller units (primary particles) that aggregate in an oriented manner. In this report we influence this aggregation by adding salt to the ongoing synthesis, generating well-ordered hexagonal p6m structure (SBA-15), with varying particle diameters. The additions, with either NaCl or NaI, were made at a time corresponding to the onset of oriented aggregation. Both salts promote the aggregation and particles with diameters of up to 5 microm were obtained. The thickness, about 0.4 microm, of the particles was retained, in accordance with the proposed growth mechanism. The aggregation characteristic was dependent on the salt used and the concentration of the salt. Both the cation and the anion were found to influence the aggregation. Having salt present already at the start of the synthesis gave a different product. The particle formation process depends on an interplay between attractive and repulsive forces between aggregates. We interpret the observed effect of salt addition to a medium which already has a very high ionic strength (1.6 M HCl) as due to ion binding to the combined polyethylene oxide-silica brush at the particles surface. PMID- 20358080 TI - Photoabsorption spectra of a natural polyphenol compound for therapeutic applications: the protocatechuic acid in dilute water solution at room temperature. AB - The UV-Vis absorption spectra of the protocatechuic acid, a potential new drug for the treatment of cancerous tumors and central nervous diseases, is for the first time fully reproduced in water solution at room temperature; these results open up the routes to integrated experimental/simulated studies in order to identify characteristic spectroscopic features of such a molecule and its derivatives within different hosting receptors in nature. PMID- 20358081 TI - Inorganic ammonium salts and carbonate salts are efficient catalysts for aldol condensation in atmospheric aerosols. AB - In natural environments such as atmospheric aerosols, organic compounds coexist with inorganic salts but, until recently, were not thought to interact chemically. We have recently shown that inorganic ammonium ions, NH(4)(+), act as catalysts for acetal formation from glyoxal, a common atmospheric gas. In this work, we report that inorganic ammonium ions, NH(4)(+), and carbonate ions, CO(3)(2-), are also efficient catalysts for the aldol condensation of carbonyl compounds. In the case of NH(4)(+) this was not previously known, and was patented prior to this article. The kinetic results presented in this work show that, for the concentrations of ammonium and carbonate ions present in tropospheric aerosols, the aldol condensation of acetaldehyde and acetone could be as fast as in concentrated sulfuric acid and might compete with their reactions with OH radicals. These catalytic processes could produce significant amounts of polyconjugated, light-absorbing compounds in aerosols, and thus affect their direct forcing on climate. For organic gases with large Henry's law coefficients, these reactions could also result in a significant uptake and in the formation of secondary organic aerosols (SOA). This work reinforces the recent findings that inorganic salts are not inert towards organic compounds in aerosols and shows, in particular, that common ones, such as ammonium and carbonate salts, might even play important roles in their chemical transformations. PMID- 20358082 TI - Classical description in a quantum spirit of the prototype four-atom reaction OH + D2. AB - Classical mechanics is the only practical way to simulate internuclear motion in many complex systems that are important for biology, materials science, and technology. It is therefore important to test classical dynamics on simpler systems. The OH + H(2) or OH + D(2) system is the prototype four-body chemical reaction for fundamental studies of this nature, and high-resolution experiments have been reported by Davis and co-workers. Here we use those experiments to test state-resolved quasi-classical trajectory calculations in a quantum spirit, and find good agreement with experiment. Our simulations correctly predict that the newly formed oxygen-deuterium bond in the HOD product is preferentially excited to the vibrational state v = 2, and they yield a state-resolved product translational energy distribution. Of special interest is that the triple (angle velocity) differential cross section shows the same state-resolved structure associated with the product vibrational states that were analyzed. This level of accuracy has previously been achieved only for triatomic systems, and these new simulations demonstrate that the quasi-classical method with quantum corrections may represent a reasonable alternative to quantum scattering approaches for the description of polyatomic reaction dynamics. PMID- 20358083 TI - Templates for wax deposition? AB - Molecular dynamics simulations have been used to study the behaviour of a liquid mixture of octacosane and heptane between two planar hematite surfaces; one of the surfaces was coated by a monolayer of an imidazoline-based corrosion inhibitor (CI). It was found that the octacosane could be inserted into the CI monolayer when it was aligned with the alkyl tails of the CIs, but the rate for such an insertion was slow. Potential of mean force calculations confirmed that there is a free energy barrier to insertion of octacosane into the CI film, and identified a secondary minimum about 13 A from the surface as a metastable intermediate for insertion. A much more rapid process was adsorption of the octacosane onto the exposed hematite (1012) surface, forming multiple layers and with a packing that was reminiscent of the octacosane crystal structure but with an orientation that matched the topology of the haematite surface. PMID- 20358084 TI - Extra-framework aluminium species in hydrated faujasite zeolite as investigated by two-dimensional solid-state NMR spectroscopy and theoretical calculations. AB - Extra-framework aluminium (EFAL) species in hydrated dealuminated HY zeolite were thoroughly investigated by various two-dimensional solid-state NMR techniques as well as density functional theoretical calculations. (27)Al MQ MAS NMR experiments demonstrated that five-coordinated and four-coordinated extra framework aluminium subsequently disappeared with the increase of water loading, and the quadrupole interaction of each aluminium species decreased gradually during the hydration process. (1)H double quantum MAS NMR revealed that the EFAL species in the hydrated zeolite consisted of three components: a hydroxyl AlOH group, and two types of water molecule (rigid and mobile water). (1)H-(27)Al LG CP HETCOR experiments indicated that both the extra-framework and the framework Al atoms were in close proximity to the rigid water in the fully rehydrated zeolite. The experimental results were further confirmed by DFT theoretical calculations. Moreover, theoretical calculation results further demonstrated that the EFAL species in the hydrated zeolite consisted of the three components and the calculated (1)H NMR chemical shift for each component agreed well with our NMR observations. It is the rigid water that connects the extra-framework aluminium with the four-coordinated framework aluminium through strong hydrogen bonds. PMID- 20358085 TI - Temperature-resolved thermal analysis of cisplatin by means of Li+ ion attachment mass spectrometry. AB - Li(+) ion attachment mass spectrometry (IAMS) was evaluated as an analytical methodology for measurement of the thermally labile, nonvolatile, and insoluble compound cisplatin, which is used as an anticancer agent in the treatment of testicular and ovarian cancers. We aimed to develop an improved method for the mass spectrometric determination of cisplatin, particularly in its molecular ion form. A uniquely designed quadrupole mass spectrometry system along with a Li(+) ion attachment technique and a direct inlet probe provided cisplatin molecular ions as Li(+) ion adducts; to our knowledge this is the first reported instance of cisplatin Li(+) ion adducts. Full-scan spectra were obtained with approximately 10 microg samples. Infrared image furnace-ion attachment mass spectrometry (IIF-IAMS) also was used to study the temperature-programmed decomposition of this drug. The slope of the plot of signal intensity versus temperature for cisplatin decomposition from 225 to 249 degrees C was used to determine an apparent activation energy (E(a)) of 38.0 kcal mol(-1) for the decomposition of cisplatin. This decomposition parameter is useful for predicting drug stability (shelf life). In this study, we have demonstrated that IAMS can be a valuable technique for the direct mass spectral analysis and kinetic study of d metal complex platinum anticancer agents. PMID- 20358086 TI - Measurements of the wavelength dependent extinction of aerosols by cavity ring down spectroscopy. AB - Cavity ring down measurements are performed on accumulation mode aerosol, 240 nm to 700 nm in diameter, over a range in wavelength, extending from 540 to 570 nm. We demonstrate that the measured variation in extinction efficiency with wavelength can be used to retrieve the dispersion in the real part of the refractive index. These measurements are contrasted with previous aerosol cavity ring down studies which have focussed on investigating the variation in optical extinction with particle size parameter through a variation in the sampled particle size distribution. In the measurements reported here, the gradient in the optical extinction can be recorded with fine resolution in size parameter (approximately 0.02) through variation in laser wavelength. Such an approach, as well as allowing a determination of the dispersion in refractive index, could be used to constrain the retrieval of refractive index at a single wavelength. PMID- 20358089 TI - Management of charges and excitons for high-performance white organic light emitting diodes. AB - This tutorial review highlights recent work on white organic light-emitting diodes (WOLEDs) in view of their potential as the next generation lighting source. It begins with an introduction to the fundamentals of WOLEDs, and then discusses the key factors that determine the performance of WOLEDs. The focus is on charges and excitons, which are the fundamental elements associated with the physical processes within the device. Correspondingly, the third section illustrates how to control the efficiency and color quality of WOLEDs through the management of charges and excitons. Finally, challenges and opportunities for the further improvement of device performance will be discussed. PMID- 20358090 TI - Fusion and alloying of (bi)metallic nanocrystals onto TiO2 nanowires in the presence of surface grafted polymer brushes. AB - In present paper, the fusion of metal nanocrystals on TiO2 nanowires is studied and utilized to synthesize bimetallic nanoparticles on nanowires. Cationic polydimethyl aminoethyl methacrylate (PDMAEMA) brushes are grafted onto TiO2 nanowires, and palladium nanocrystals are produced by polymer brush-bound PdCl(4)(2-) and subsequent in situ reduction with NaBH4 in high density and low polydispersity. It is found that Pd nanocrystals of 2-3 nm starts to fuse even at 100 degrees C, but are apparently obstructed by the polymer brush matrix. Nanocrystal fusion speeds up instantly after polymer decomposition degradation at temperatures above 300 degrees C. By taking advantage of the polymer brush technique successive, templated uploading of different nanoparticles and fusion, Pd-Au bimetallic nanoparticles or alloys are formed on TiO2 nanowires. The results provide a novel method towards TiO2 nanowire supported (bi)metallic nanoparticles and have hinted at practical uses for elucidating the catalytic behavior of the composites. PMID- 20358091 TI - Structure and bonding of aqueous glutamic acid from classical molecular dynamics simulations. AB - Using classical molecular dynamics we have studied the solution structure of (1:1:29) glutamate with sodium counter ions and water. We provide a structural description of the system, focusing on glutamate-glutamate interactions and providing further insight into glutamate-water interactions. In particular we have characterised the solution structure using three different water potentials, finding little difference between the structural features they predict. We find key differences in the bonding motifs for the two different carboxyl groups, both in the glutamate-glutamate and glutamate-water interactions. Finally, we have examined the hydration structure of the sodium ions in the solution, showing that 10% of the ions are fully hydrated by water, despite the high glutamate concentration. PMID- 20358092 TI - Ultrafast radiationless transition pathways through conical intersections in photo-excited 9H-adenine. AB - We performed CASSCF and MRCI calculations for determination of the effective pathways of ultrafast radiationless transitions from the optically allowed pipi* 1La state to the ground state S0 of 9H-adenine. The npi*, pisigma*, and two pipi* states were taken into account as states involved in the radiationless process. Optimized geometry and conical intersections were searched in the full dimensional space for the vibrational degrees of freedom by using the suite of quantum chemistry codes MOLPRO. The MRCI transition energies to excited states are in good agreement with the experimental values. The mechanisms of three competing pathways, two indirect pathways via the pisigma* and npi* states, 1La >pisigma*->S0 and 1La->npi*-> S0, and a direct pathway 1La->S0, were examined on the basis of the structures and energies of conical intersections involved in ultrafast radiationless transitions from 1La to S0. Any conical intersection between the pisigma* and npi* states was not found. This suggests that the two indirect pathways are independent of each other. The pipi* 1La-pisigma* conical intersection lies higher than the pipi* 1La state at the Franck-Condon geometry by 0.19 eV according to the present MRCI calculation, which is consistent with the experimental observation that a new channel is open at the excess energy of 0.2 eV above the band origin of the pipi* 1La state. It is concluded that relaxation from the pipi* 1La-pisigma* conical intersection to S0 occurs mainly through the pisigma*-S0 conical intersection. The pipi* 1La-npi* conical intersection lies higher by 0.1 eV (MRCI value) than the pipi* 1La state at the Franck-Condon geometry. The fast decay component in time-resolved spectra of 9H adenine is attributed to rapid radiationless transitions to the npi* state via this conical intersection followed by the transition to S0 via the npi*-S0 (or pipi* 1La-S0) conical intersection. The pipi* 1La-S0 conical intersection of large out-of-plane distortion has the lowest energy among the conical intersections found in this study. We identified the transition state between the pipi* 1La at the Franck-Condon geometry and the pipi* 1La-S0 conical intersection. The MRCI energy of the transition state on the 1La potential surface is higher by 0.21 eV than the vertical excitation energy. The possibility of strong coupling between the two close-lying states 1La and npi* indicates that, besides this direct pathway, radiationless transitions to S0 via the pipi* 1La-S0 conical intersection can also occur after rapid relaxations between 1La and npi*. The analysis of the h-vector for each conical intersection has shown that the active coupling for the pisigma* pathway is dominated by the out-of plane normal mode nu10, while the active coupling for the npi* pathway is distributed among many normal modes. Control of the branching ratio of the two indirect pathways can be achieved by selective excitation of single vibronic levels involving active coupling modes such as the mode nu10. PMID- 20358093 TI - Coordination of Cu(2+)and Ni(2+) with the histone model peptide of H2B N-terminal tail (1-31 residues): A spectroscopic study. AB - The interaction of Cu(2+) and Ni(2+) with the N-terminal tail of histone H2B, the 31 amino acid peptide H2B(1-31) (Ac-PEPAKSAPAPKKG(13)SKKAVTKAQKKD(25)GKKRKR NH(2)), studied by various spectroscopic techniques (UV/Vis, CD, EPR and NMR) are described. The results showed the formation of Cu(2+)-H2B(1-31) complexes above pH 7.3 most probably through the beta-carboxylate group of D25. With the increase of the pH, a mixture of 3 N and 4 N species presenting {2N(-), CO, epsilonNH(2)} and {2N(-), OH(2), epsilonNH(2)}{epsilonNH(2)} coordination modes, respectively is formed, while at highly basic solutions the binding of an additional amide donor is suggested. NMR spectroscopy supported by CD spectroscopy indicated that Ni(2+) coordination takes place most likely through Q22-K23-K24-D25 peptide fragment. Direct coordination to Ni(2+), in a {4N(-)} coordination mode, with a severe conformation change in all residues from G13 to G26 was observed. Cu(2+) and Ni(2+) binding to the N-terminal tail of H2B causes a severe conformational change that might interfere with histone post-translational modifications, possibly leading to epigenetic changes. PMID- 20358094 TI - Organocatalytic kinetic resolution via intramolecular aldol reactions: enantioselective synthesis of both enantiomers of chiral cyclohexenones. AB - Kinetic resolution of 6-aryl-2,6-hexanediones was achieved with chiral secondary amine catalyzed intramolecular aldolization. The current kinetic resolution protocol enables the synthesis of both enantiomers of cyclohexenones with moderate to good enantioselectivity. PMID- 20358095 TI - Seven-component reactions by sequential chemoselective Ugi-Mumm/Ugi-Smiles reactions. AB - A seven-component reaction was accomplished by utilizing the different chemoselectivities of the Ugi-Mumm and the Ugi-Smiles reaction. The sequential multicomponent reactions led to highly diverse peptide and glycopeptide like structures. PMID- 20358096 TI - Nanohole arrays in chemical analysis: manufacturing methods and applications. AB - Since the last decade, nanohole arrays have emerged from an interesting optical phenomenon to the development of applications in photophysical studies, photovoltaics and as a sensing template for chemical and biological analyses. Numerous methodologies have been designed to manufacture nanohole arrays, including the use of focus ion beam milling, soft-imprint lithography, colloidal lithography and, more recently, modified nanosphere lithography (NSL). With NSL or colloidal lithography, the experimental conditions control the density of the nanosphere mask and, thus, the aspect of the nanohole arrays. Low surface coverage of the nanosphere mask produces disordered nanoholes. Ordered nanohole arrays are obtained with a densely packed nanosphere mask in combination with electrochemical deposition of the metal, glancing angle deposition (GLAD) or etching of the nanospheres prior to metal deposition. A review of these methodologies is presented here with an emphasis on the optical properties of nanoholes interesting in analytical chemistry. In particular, applications of these novel plasmonic materials will be demonstrated as substrates for a localized surface plasmon resonance (LSPR), Surface Plasmon Resonance (SPR), surface enhanced Raman spectroscopy (SERS), and in electrochemistry with nano patterned electrodes. PMID- 20358097 TI - A butenolide intermediate in methylenomycin furan biosynthesis is implied by incorporation of stereospecifically 13C-labelled glycerols. AB - The label from [3-(13)C]-L-glycerol is incorporated into the hydroxymethyl group of methylenomycin furans suggesting a butenolide intermediate in their biosynthesis. PMID- 20358102 TI - Microfluidic cell culture systems for drug research. AB - In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted. PMID- 20358103 TI - Nanofluidic technology for biomolecule applications: a critical review. AB - In this review, we present nanofluidic phenomena, particularly as they relate to applications involving analysis of biomolecules within nanofabricated devices. The relevant length scales and physical phenomena that govern biomolecule transport and manipulation within nanofabricated nanofluidic devices are reviewed, the advantages of nanofabricated devices are presented, and relevant applications are cited. Characteristic length scales include the Debye length, the Van der Waals radius, the action distance of hydrogen bonding, the slip length, and macromolecular dimensions. On the basis of the characteristic lengths and related nanofluidic phenomena, a nanofluidic toolbox will be assembled. Nanofluidic phenomena that affect biomolecule behavior within such devices can include ion depletion and enrichment, modified velocity and mobility, permselectivity, steric hindrance, entropy, adsorption, and hydrodynamic interaction. The complex interactions and coupled physics of such phenomena allow for many applications, including biomolecule separation, concentration, reaction/hybridization, sequencing (in the case of DNA) and detection. Examples of devices for such applications will be presented, followed by a discussion of near-term challenges and future thoughts for the field. PMID- 20358104 TI - Electrokinetic label-free screening chip: a marriage of multiplexing and high throughput analysis using surface plasmon resonance imaging. AB - We present an electrokinetic label-free biomolecular screening chip (Glass/PDMS) to screen up to 10 samples simultaneously using surface plasmon resonance imaging (iSPR). This approach reduces the duration of an experiment when compared to conventional experimental methods. This new device offers a high degree of parallelization not only for analyte samples, but also for multiplex analyte interactions where up to 90 ligands are immobilized on the sensing surface. The proof of concept has been demonstrated with well-known biomolecular interactant pairs. The new chip can be used for high throughput screening applications and kinetics parameter extraction, simultaneously, of interactant-protein complex formation. PMID- 20358105 TI - Platelet retraction force measurements using flexible post force sensors. AB - Platelets play an important role in hemostasis by forming a thrombotic plug that seals the vessel wall and promotes vascular healing. After platelets adhere and aggregate at the wound site, their next step is to generate contractile forces through the coordination of physicochemical interactions between actin, myosin, and alpha(IIb)beta(3) integrin receptors that retract the thrombus' size and strengthen its adhesion to the exposed matrix. Although platelet contractile forces (PCF) are a definitive feature of hemostasis and thrombosis, there are few approaches that can directly measure them. In this study, we describe the development of an approach to measure PCF in microthrombi using a microscopic flexible post force sensor array. Quasi-static measurements and live microscopic imaging of thrombin-activated platelets on the posts were conducted to assay the development of PCF to various hemostatic conditions. Microthrombi were observed to produce forces that monotonically increased with thrombin concentration and activation time, but forces subsided when thrombin was removed. PCF results were statistically similar on arrays of posts printed with fibronectin or fibrinogen. PCF measurements were combined with clot volume measurements to determine that the average force per platelet was 2.1 +/- 0.1 nN after 60 min, which is significantly higher than what has been measured with previous approaches. Overall, the flexible post arrays for PCF measurements are a promising approach for evaluating platelet functionality, platelet physiology and pathology, the impacts of different matrices or agonists on hemostatic responses, and in providing critical information regarding platelet activity that can guide new hemostatic or thrombotic strategies. PMID- 20358106 TI - Building and manipulating neural pathways with microfluidics. AB - Communication between different brain regions, and between local circuits in the same brain region, is an important area of study for basic and translational neuroscience research. Selective and chronic manipulation of one of the components in a given neural pathway is frequently required for development and plasticity studies. We designed an in vitro platform that captures some of the complexity of mammalian brain pathways but permits easy experimental manipulation of their constituent parts. Organotypic cultures of brain slices were carried out in compartments interconnected by microchannels. We show that co-cultures from cortex and hippocampus formed functional connections by extending axons through the microchannels. We report synchronization of neural activity in co-cultures, and demonstrate selective pharmacological manipulation of activity in the constituent slices. Our platform enables chronic, spatially-restricted experimental manipulation of pre- and post-synaptic neurons in organotypic cultures, and will be useful to investigators seeking to understand development, plasticity, and pathologies of neural pathways. PMID- 20358107 TI - Combined microfluidics/protein patterning platform for pharmacological interrogation of axon pathfinding. AB - Assembly of functional neural circuits relies on the ability of axons to navigate a complex landscape of guidance cues in the extracellular environment. In this report, we investigate localized cell signaling in response to these cues by combining a microfabricated compartmentalization chamber with multicomponent, protein-micropatterned surfaces; this system offers improved spatial resolution and new capabilities for targeted manipulation of neuronal axons. We illustrate the potential of this system by addressing the role of fibroblast growth factor receptor (FGFR) signaling in modulating axon guidance by N-cadherin. Motor neurons that were derived from embryonic stem cells extend axons from one compartment through a microchannel barrier and into a second compartment containing patterns of N-cadherin, against a background of laminin. N-cadherin was effective in both guiding and accelerating motor axon outgrowth. Using the chamber system to target the application of pharmacological agents to specific parts of the neuron, we demonstrate that FGFR signaling in the axon but not the cell body increases the rate of axon outgrowth while not affecting guidance along N-cadherin. These results demonstrate that cell signaling must take into account the spatial layout of the cell. This new platform provides a powerful tool for understanding such effects over a wide range of signaling systems. PMID- 20358108 TI - Lab-On-a-Chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB). AB - We describe a new eight channel Lab-On-a-Chip (LOC) for a Carbon Nanotube (CNT) based immunoassay with optical detection of Staphylococcal Enterotoxin B (SEB) for food safety applications. In this work, we combined four biosensing elements: (1) CNT technology for primary antibody immobilization, (2) Enhanced Chemiluminescence (ECL) for light signal generation, (3) a cooled charge-coupled device (CCD) for detection and (4) polymer lamination technology for developing a point of care immunological assay for SEB detection. Our concept for developing versatile LOCs, which can be used for many different applications, is to use a modular design with interchangeable recognition elements (e.g. various antibodies) to determine the specificity. Polymer lamination technology was used for the fabrication of a six layer, syringe operated LOC capable of analyzing eight samples simultaneously. An anti-SEB antibody-nanotube mixture was immobilized onto a polycarbonate strip, to serve as an interchangeable ligand surface that was then bonded onto the LOC. SEB samples are loaded into the device and detected by an ELISA assay using Horse Radish Peroxidase (HRP) conjugated anti-SEB IgG as a secondary antibody and ECL, with detection by a previously described portable cooled CCD detector. Eight samples of SEB in buffer or soy milk were assayed simultaneously with a limit of detection of 0.1 ng mL(-1). CNT immobilization of the antibody increased the sensitivity of detection six fold. Use of a simple interchangeable immunological surface allows this LOC to be adapted to any immunoassay by simply replacing the ligand surface. A syringe was used to move fluids for this assay so no power is needed to operate the device. Our versatile portable point-of-care CCD detector combined with the LOC immunoassay method described here can be used to reduce the exposure of users to toxins and other biohazards when working outside the lab, as well as to simplify and increase sensitivity for many other types of immunological diagnostics and detection assays. PMID- 20358109 TI - On-chip determination of spermatozoa concentration using electrical impedance measurements. AB - In this article we describe the development of a microfluidic chip to determine the concentration of spermatozoa in semen, which is a main quality parameter for the fertility of a man. A microfluidic glass-glass chip is used, consisting of a microchannel with a planar electrode pair that allows the detection of spermatozoa passing the electrodes using electrical impedance measurements. Cells other than spermatozoa in semen also cause a change in impedance when passing the electrodes, interfering with the spermatozoa count. We demonstrate that the change in electrical impedance is related to the size of cells passing the electrodes, allowing to distinguish between spermatozoa and HL-60 cells suspended in washing medium. In the same way we are able to distinguish between polystyrene beads and spermatozoa. Thus, by adding a known concentration of polystyrene beads to a boar semen sample, the spermatozoa concentrations of seven mixtures are measured and show a good correlation with the actual concentration (R(2)-value = 0.97). To our knowledge this is the first time that the concentration of spermatozoa has been determined on chip using electrical impedance measurements without a need to know the actual flow speed. The proposed method to determine the concentration can be easily applied to other cells. The described on-chip determination of the spermatozoa concentration is a first step towards a microfluidic system for a complete quality analysis of semen. PMID- 20358110 TI - Diffusive spreading of time-dependent pressures in elastic microfluidic devices. AB - Here we show that transient flow of Newtonian fluids in viscoelastic PDMS microfluidic channels can be described by a diffusive pressure spreading mechanism analogous to the electric telegrapher's equation. The pressure diffusion constant D(p) = 1/R(x)C(x) of a channel with length l is determined by the hydrodynamic resistance R(x) and capacitance C(x) per unit length of the channel. l(2)/D(p) sets the timescale for the transmission of pressure steps along the channel and the relaxation after a pressure step in steady state flow. For oscillatory flows, the channel acts as a low-pass filter with a cutoff frequency omega(cutoff) = 2piD(p)l(-2), so that pressure and flow rate pulses disperse and get smoothed while they travel along the channel. The combination of different microparticle tracking techniques allows the determination of pressure and flow profiles at any point in the channel and excellent agreement with theoretical predictions is obtained. PMID- 20358111 TI - The integration of 3D carbon-electrode dielectrophoresis on a CD-like centrifugal microfluidic platform. AB - We introduce the integration of a novel dielectrophoresis (DEP)-assisted filter with a compact disk (CD)-based centrifugal platform. Carbon-electrode dielectrophoresis (carbon-DEP) refers to the use of carbon electrodes to induce DEP. In this work, 3D carbon electrodes are fabricated using the C-MEMS technique and are used to implement a DEP-enabled active filter to trap particles of interest. Compared to traditional planar metal electrodes, 3D carbon electrodes allow for superior filtering efficiency. The system includes mounting modular 3D carbon-DEP chips on an electrically interfaced rotating disk. This allows simple centrifugal pumping to replace the large footprint syringe pump approaches commonly used in DEP systems. The advantages of the CD setup include not only a reduced footprint, but also complexity and cost reduction by eliminating expensive precision pumps and fluidic interconnects. To demonstrate the viability of this system we quantified the filter efficiency in the DEP trapping of yeast cells from a mix of latex and yeast cells. Results demonstrate selective filtering at flow rates up to 35 microl min(-1). The impact of electrode height, DEP chip misalignment and particle sedimentation on filter efficiency and the advantages this system represents are analyzed. The ultimate goal is to obtain an automated platform for bioparticle sorting with application in different fields such as point-of-care diagnostics and cell-based therapies. PMID- 20358112 TI - Lateral patch-clamping in a standard 1536-well microplate format. AB - Lateral patch-clamping has emerged as a chip-based platform for automation of the conventional patch-clamp technique, the 'gold' standard for studying cellular ion channels. The conventional technique, as it relies on skilled-maneuver of glass micropipettes to patch cells, is extremely delicate, low in throughput, and thus cannot be used for primary screening of compounds against ion channels. Direct integration of glass capillaries on silicon provides lateral junctions for automated trapping and patching of cells. We demonstrate here a method of scaling up the lateral junctions to a standard 1536-well microtiter plate format. A single unit of 1536-well plate has been formed here on a 9 mm by 9 mm microstructured silicon with the inclusive of 16 wells molded in a capping layer made of polydimethylsiloxane (PDMS). The silicon substrate provides integrated glass capillaries (total 12) and their associated microfluidic network. Each glass capillary has an independent access through a dedicated well in PDMS and leads to a centralized channel in which cell suspension can be delivered through one of the remaining 4 wells. The unit has been tested on RBL-1 cells by recording whole-cell activity from inwardly rectifying endogenous potassium channels. A revised test protocol has been prescribed to avoid inaccurate readings due to altered ionic composition of the recording buffer when a typical suction is applied to capture cells. PMID- 20358113 TI - Polypropylene CD-organic light-emitting diode biosensing platform. AB - This paper describes the development of a compact platform for simultaneous photoluminescence (PL)-based sensing of multiple bioanalytes using a lab-on-CD. The platform is based on microfluidic features generated on foamed polypropylene (PP) surfaces by ultrasonic micro-embossing, sub-micron thick organic light emitting diode (OLED) pixels that serve as the PL excitation sources, and a compatible array of compact photodetectors (PDs). The localized heating resulting from the ultrasonic micro-embossing enables generation of flash-free micro patterns on the foamed PP surfaces. The embossed features are designed to function as reservoirs, channels, valves, and reaction chambers, to allow, in combination with compact OLED/PD arrays, the simultaneous monitoring of glucose, lactate, ethanol, and dissolved oxygen (DO) in four separate single CD segments using a standard PC-CD player. The analytes' concentrations are determined following CD rotation for reagent mixing by measuring the DO level via the PL decay time of an oxygen-sensitive dye following an OLED excitation pulse. Glucose, lactate, and ethanol are monitored following their oxidation in sealed cells in the presence of oxygen and their specific oxidase enzyme, which results in consumption of DO. Calibration curves for each of the analytes and their concentrations in mixtures were monitored on the four separate segments of the bio-CD. The attributes and utility of the compact OLED-bio-CD-PD platform for sensitive and accurate monitoring of multiple analytes, and its potential field deployability, are discussed. PMID- 20358114 TI - High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios. AB - We demonstrate the use of high-speed, multiphoton absorption polymerization (MAP) for the fabrication of large-area microfluidic master structures. High-speed fabrication in SU8 without laser-induced damage is made possible by the use of a novel photoacid generator with a high two-photon-absorption cross-section. Master structures fabricated with MAP can be used to produce polydimethylsiloxane microchannels with high aspect ratios and/or arbitrary cross-sections. Microchannels with different cross-sections and heights can be combined readily in a single device. This fabrication technique significantly increases the diversity of channel architectures available for microfluidic devices. PMID- 20358115 TI - Planar digital nanoliter dispensing system based on thermocapillary actuation. AB - We provide guidelines for the design and operation of a planar digital nanodispensing system based on thermocapillary actuation. Thin metallic microheaters embedded within a chemically patterned glass substrate are electronically activated to generate and control 2D surface temperature distributions which either arrest or trigger liquid flow and droplet formation on demand. This flow control is a consequence of the variation of a liquid's surface tension with temperature, which is used to draw liquid toward cooler regions of the supporting substrate. A liquid sample consisting of several microliters is placed on a flat rectangular supply cell defined by chemical patterning. Thermocapillary switches are then activated to extract a slender fluid filament from the cell and to divide the filament into an array of droplets whose position and volume are digitally controlled. Experimental results for the power required to extract a filament and to divide it into two or more droplets as a function of geometric and operating parameters are in excellent agreement with hydrodynamic simulations. The capability to dispense ultralow volumes onto a 2D substrate extends the functionality of microfluidic devices based on thermocapillary actuation previously shown effective in routing and mixing nanoliter liquid samples on glass or silicon substrates. PMID- 20358116 TI - A reconfigurable optofluidic Michelson interferometer using tunable droplet grating. AB - This paper presents a novel optofluidic Michelson interferometer based on droplet microfluidics used to create a droplet grating. The droplet grating is formed by a stream of plugs in the microchannel with constant refractive index variation. It has a real-time tunability in the grating period through varying the flow rates of the liquids and index variation via different combinations of liquids. The optofluidic Michelson interferometer is highly sensitive and is suitable for the measurement of biomedical and biochemical buffer solutions. The experimental results show that it has a sensitivity of 66.7 nm per refractive index unit (RIU) and a detection range of 0.086 RIU. PMID- 20358117 TI - Infrared light induced patterning of proteins on ppNIPAM thermoresponsive thin films: a "protein laser printer". AB - Protein micropatterns have applications in fundamental life sciences and clinical medicine. In this work, we present a new technique to create 2-D protein micropatterns by local activation of a thin film of thermoresponsive plasma deposited poly(N-isopropylacrylamide) (ppNIPAM) using a computer-controlled infrared laser beam. While the whole substrate is exposed to the protein solution, protein deposition happens only at laser-activated locations. A few seconds of laser exposure is all that is required to form a pattern with resolution in the single micrometre range. Successful ligand binding after protein deposition indicates that protein function remains intact after laser induced adsorption onto ppNIPAM. This rapid, simple technique advances currently available strategies for protein patterning by its potential to pattern proteins in an enclosed environment or onto a 3-D scaffold. PMID- 20358118 TI - Enclosed pillar arrays integrated on a fluidic platform for on-chip separations and analysis. AB - Due to the difficulty of reliably producing sealed 3-D structures, few researchers have tackled the challenges of creating pillar beds suitable for miniaturized liquid phase separation systems. Herein, we describe an original processing sequence for the fabrication of enclosed pillar arrays integrated on a fluidic chip which, we believe, will further stimulate interest in this field. Our approach yields a mechanically robust enclosed pillar system that withstands mechanical impacts commonly incurred during processing, sealing and operation, resulting in a design particularly suitable for the research environment. A combination of a wafer-level fabrication sequence with chip-level elastomer bonding allows for chip reusability, an attractive and cost efficient advancement for research applications. The characteristic features in the implemented highly ordered pillar arrays are scalable to submicron dimensions. The proposed fluidic structures are suitable for handling picolitre sample volumes and offer prospects for substantial improvements in separation efficiency and permeability over traditional packed and monolithic columns. Our experimental observations indicate plate heights as low as 0.76 microm for a 10 mm long pillar bed. Theoretical calculations confirm that ordered pillar arrays with submicron pore sizes combine superior analysis speed, picolitre sample volumes, high permeability and reasonably large plate numbers on a small footprint. In addition, we describe a fluidic interface that provides streamlined coupling of the fabricated structures with off-chip fluidic components. PMID- 20358120 TI - Selective separation of larger molecules from a Lewis-base mixture by flexible one-dimensional Cu(II) coordination polymer with shape-recognizing space. AB - A flexible one-dimensional Cu(II) coordination polymer with shape-recognizing space shows selective adsorption of larger 2-butanone guests from Lewis-base mixtures containing 2-butanone-EtOH or 2-butanone-MeOH. PMID- 20358121 TI - Dynamical model for assessment of anti-angiogenic therapy of cancer. AB - Different experimental models have substantially established that the anti angiogenic (AAG)group of drugs are able to control the growth of tumor mass by cutting down the nutritive supply to the cancer cells. The mechanism of action of this group of drugs acts on the cells of the vascular endothelium. Recently, different AAG drugs have been in clinical trials. Initial clinical trials showed that application of AAG drugs produced different sorts of toxicity in patients,so calibration of the doses and drug application schedules are very important at present.Hence, development of analytical models would definitely help in this respect, particularly atthe individual level. The analytical model presented here may help to make a judicious choice of drug doses and drug schedule to control the growth of the tumor system under the condition of malignancy. PMID- 20358122 TI - Oligo(amidoamine)s hydrogels with tunable gel properties. AB - A series of oligo(amidoamine)s (OAAs) that can be reversibly switched between sol and gel phases upon changes in pH and temperature have been synthesized and characterized. Their viscoelastic properties were significantly increased upon increasing the number of methylene groups, implying that viscoelasticity could clearly be tuned at the molecular level. PMID- 20358123 TI - Uptake and phototoxicity of meso-tetrahydroxyphenyl chlorine are highly variable in human biliary tract cancer cell lines and correlate with markers of differentiation and proliferation. AB - Photodynamic therapy (PDT) using Photofrin and, recently, Foscan has gained broad acceptance for palliative treatment of non-resectable cholangiocarcinoma (CC). No information, however, is available whether the phenotype of CC tumour cells has an effect on the efficiency of the treatment. Using a well-characterised set of n = 9 biliary tract cancer cell lines this study investigated the uptake, phototoxicity, and release of meso-tetrahydroxyphenyl chlorine (mTHPC, Foscan) after incubation with 200 or 400 ng ml(-1) mTHPC. For uptake of mTHPC we found great variations between the individual cell lines (up to a factor 2), resulting in even more pronounced differences in phototoxicity. Based on statistical classification by hierarchical cluster analysis, two groups of cell lines can be distinguished which are characterised by either high or low susceptibility towards mTHPC-based photodynamic treatment. Correlation analysis with previously established immunochemical parameters showed that cells with a low cytokeratin-19 (ductal differentiation), high vimentin (mesenchymal marker), and high proliferative phenotype preferentially show higher uptake of mTHPC and subsequent phototoxicity. These results demonstrate high variability of biliary tract cancer cells when subjected to mTHPC-based photodynamic treatment and identify possible markers that could be used in the clinical setting in order to predict the efficiency of PDT and adjust the dose for complete tumour elimination. PMID- 20358124 TI - Synthesis of chiral polyazamacrocycles of variable ring size. AB - Synthesis and structure elucidation of optically active tri-, tetra-, and penta azamacrocycles having 4-methoxyphenyl pendants are described. Regioselective ring opening of a nosylaziridine with secondary benzyl amines was repeatedly performed to afford the cyclization precursors. Intramolecular N-alkylation of N-(omega haloalkyl) nosylamide provided tri-, tetra-, and penta-azamacrocycles. On the basis of our study of the tetra-azamacrocycle previously elucidated by X-ray single-crystal analysis and in solution by NMR analysis, we conclude that the tri azamacrocycle does not mainly have a vase-type conformation because of the steric hindrance of the 4-methoxyphenyl groups but the penta-azamacrocycle has a vase type conformation in CDCl(3) and in CD(2)Cl(2). The vase-type conformation of the penta-azamacrocycle is, however, not as much stable as that observed in the tetra azamacrocycle because conformational flexibility of the penta-azamacrocycle was observed in deuterated benzene. PMID- 20358125 TI - Asymmetric epoxidation of 2-arylidene-1,3-diketones: facile access to synthetically useful epoxides. AB - In this article the first enantioselective epoxidation reaction of acyclic and cyclic 2-arylidene-1,3-diketones is reported. Easily accessible or commercially available alpha,alpha-diaryl prolinols as the organocatalysts in the presence of tert-butyl hydroperoxide (TBHP) provide the corresponding epoxides in high to excellent yield (up to 99%) and up to 85% ee (ee >90% after crystallisation). These epoxides are pharmaceutically important building blocks and intermediates for the synthesis of densely functionalised epoxide derivatives. PMID- 20358127 TI - Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases. PMID- 20358126 TI - A photo- and electrochemically-active porphyrin-fullerene dyad electropolymer. AB - A hole- and electron-conducting polymer has been prepared by electropolymerization of a porphyrin-fullerene monomer. The porphyrin units are linked by aminophenyl groups to form a linear chain in which the porphyrin is an integral part of the polymer backbone. The absorption spectrum of a film formed on indium-tin-oxide-coated glass resembles that of a model porphyrin-fullerene dyad, but with significant peak broadening. The film demonstrates a first oxidation potential of 0.75 V vs. SCE, corresponding to oxidation of the porphyrin polymer, and a first reduction potential of -0.63 V vs. SCE, corresponding to fullerene reduction. Time-resolved fluorescence studies show that the porphyrin first excited singlet state is strongly quenched by photoinduced electron transfer to fullerene. Transient absorption investigations reveal that excitation generates mobile charge carriers that recombine by both geminate and nongeminate pathways over a large range of time scales. Similar studies on a related polymer that lacks the fullerene component show complex, laser-intensity-dependent photoinduced electron transfer behavior. The properties of the porphyrin-fullerene electropolymer suggest that it may be useful in organic photovoltaic applications, wherein light absorption leads to charge separation within picoseconds in a "molecular heterojunction" with no requirement for exciton migration. PMID- 20358128 TI - Lability of metal complexes at spherical sensors. Dynamic voltammetric measurements. AB - The diffusive-kinetic steady-state (dkss) approximation is applied to the case of a metal ion reaching a transforming/consuming spherical surface (sensor) when the ion is involved in a complexation reaction in solution. Simple time-dependent expressions for the surface metal flux, the lability degree and the half-wave potential are presented, valid for any value of the ratio of concentrations at the surface and the sensor radius. The solution presented is compared with other theoretical approaches, such as the kinetic steady state (kss) and the total steady state (tss), pointing out that the easy dkss approach is much more accurate than the tss one to study the metal flux and the lability degree for any value of the radius, from ultramicro to planar sensors. PMID- 20358129 TI - Density functional study of structural and electronic properties of bimetallic copper-gold clusters: comparison with pure and doped gold clusters. AB - The geometrical structures, relative stabilities, and electronic properties of small bare gold clusters Au(n)(lambda) and bimetallic complexes of bare metal clusters with one copper atom Au(n-1)Cu(lambda) (charge lambda = 0, +1, -1; 2 < or = n < or = 9) have been systematically investigated by means of first principles density functional calculations at the B3LYP level. The results show that the most stable isomers have a planar structure and resemble pure gold clusters in shape, and no three-dimensional isomers were obtained for neutral and anionic doped gold clusters. However, the geometries of Au(n-1)Cu(+) are found to undergo a structural change from two dimensional to three dimensional when the cluster contains 7 atoms. The calculated dissociation energy and second difference energy as a function of the cluster size exhibit a pronounced even-odd alternation phenomenon. Ionization potentials and electron detachment energies (both vertical and adiabatic) of Au(n)(lambda) and Au(n-1)Cu(lambda) clusters are discussed and compared with available experimental results. A good agreement between experimental and theoretical results suggests good prediction of the lowest energy structures for all clusters calculated in the present study. PMID- 20358130 TI - The capture of .H and .OH radicals by vitamin C and implications for the new source for the formation of the anion free radical. AB - To gain a better understanding of the antioxidation behaviors of vitamin C, the reactions between vitamin C (monoanionic form, AAH(-)) and two radicals, (.)H and (.)OH, have been investigated employing the B3LYP and BHandHLYP methods in combination with the atoms in molecules (AIM) theory and energy decomposition analyses (EDA). Both the radical additions to the five-membered ring of AAH(-) and H-abstraction reactions are explored. The reaction profiles of various reactions have been obtained. The most favorable active site to be attacked by radical addition has been confirmed to be the C2 site of AAH(-), which is different from that of the C3 site in the neutral vitamin C. The (.)OH addition reactions are essentially diffusion-controlled processes, which is in contrast to the previous reports. A new source for the formation of the principal anion free radical (AFR) of AAH(-) has been observed in the (.)OH attack process, i.e., AFR can be formed mainly from the H13 abstraction reaction involving two types of concerted proton-electron transfer (CPET) mechanisms. Moreover, the binding characters and formation mechanisms of the stable reaction complex formed during the formation of AFR have been systematically investigated. PMID- 20358131 TI - Dissociative double photoionization of CO2 molecules in the 36-49 eV energy range: angular and energy distribution of ion products. AB - Dissociative double photoionization of CO(2), producing CO(+) and O(+) ions, has been studied in the 36-49 eV energy range using synchrotron radiation and ion-ion coincidence imaging detection. At low energy, the reaction appears to occur by an indirect mechanism through the formation of CO(+) and an autoionizing state of the oxygen atom. In this energy range the reaction leads to an isotropic distribution of products with respect to the polarization vector of the light. When the photon energy increases, the distribution of products becomes anisotropic, with the two ions preferentially emitted along the direction of the light polarization vector. This implies that the molecule photoionizes when oriented parallel to that direction and also that the CO(2)(2+) dication just formed dissociates in a time shorter than its typical rotational period. At low photon energy, the CO(+) and O(+) product ions separate predominantly with a total kinetic energy between 3 and 4 eV. This mechanism becomes gradually less important when the photon energy increases and, at 49 eV, a process where the two products separate with a kinetic energy between 5 and 6 eV is dominant. PMID- 20358132 TI - Synthesis, structures, adsorption behaviour and magnetic properties of a new family of polynuclear iron clusters. AB - Solvothermal reactions of 1,10-phenanthroline-2,9-dicarbaldehyde dioxime (H(2)phendox) with FeCl(3).6H(2)O or FeBr(3) under solvothermal conditions yielded two trinuclear iron(III) clusters [Fe(III)(3)(mu(3) O)(phendox)(3)]X.14H(2)O (X = Cl 1.14H(2)O, Br 2.14H(2)O) and three hexanuclear iron(III) and iron(II) clusters, [Fe(III)(6)(mu(4) O)(2)(MeO)(6)X(4)(phendox)(2)].MeOH (X = Cl , Br 4) and (H(3)O)[Fe(II)(6)(mu(6) Cl)(phenda)(6)].6H(2)O (5.6H(2)O). The phendox(2-) ligand is very useful in constructing magnetically active and stable high-nuclearity metal clusters in that the phenanthroline rings and the oxime nitrogen atoms grasp the metal ions tightly while the two oxygen atoms on the oximates can link other metal centres in the shortest pairwise magnetic exchange pathway. Adjacent Fe(3)(mu(3) O)(phendox)(3)(+) motifs in 1 and 2 are packed by off-set pi-pi interactions of the aromatic rings on phendox(2-) to generate a 3D supramolecular architecture in the honeycomb topology and with 1D hexagonal channels in the dimension of 13 x 13 A along the c-axis. 2 is stable upon the removal of guest molecules and the desolvated compound absorbed considerable amount of N(2), CO(2) and H(2). 3 and 4 are isostructural. Two mu(4)-O(2-) and two phendox(2-) units link four metal atoms into a coplanar butterfly-shaped unit with the mu(4)-O(2-) slightly above and below the plane (+/-0.264 A). The other two Fe(III) ions are capped on the alternate planes via the three bridging mu(2)-methoxides and accordingly form an unprecedented hexanuclear Fe(III) cluster. Furthermore, the oximes underwent hydrolysis to yield carboxylate groups and the resulted 1,10-phenanthroline-2,9 dicarboxylate link the iron atoms to form a hexanuclear cluster of 5. Magnetic studies show that the antiferromagnetic interactions are present in the Fe(3)O core of 2 and in the (mu(6)-Cl)Fe(6)(mu-O)(12) core of 5. PMID- 20358133 TI - fac-Specific syntheses of homochiral [Fe(NN)3]2+ complexes (NN = pyridine keto hydrazone); origins of the stereoselectivity. AB - The 2-pyridinehydrazones (from condensation of pyridine-2-carbaldehyde and hydrazines) have previously been noted to have poor ligating ability as a result of a sterically demanding planar conformation. Destabilisation of this conformation is achieved through simple use of the ketohydrazones, and as a result the diamagnetic chiral tris-bidentate diimine complexes fac-[FeL3]2+ are readily isolated. In the solid state, inter-ligand - stacking and complex/counter ion H-bonding are apparent, and these features persist in solution according to dynamic NMR spectra, which also indicate extremely high stereoselectivity for the fac isomers (>200:1). The compounds crystallise as conglomerates, and time resolved CD spectra of non-racemic samples indicate a high degree of persistence of chirality (racemisation t1/2 ca 77 min). Variations of solvent and counter-ion indicate that H-bonding is unimportant in determining the structure of the cation. The fac-selectivity arises in the induction of a chiral conformation in the coordinated ligand, and the fact that such non-planar ligands can only be accommodated about the Fe(II) centre if they all have the same absolute configuration. Adding a hydrazine N-methyl group increases the steric demand further, while retaining the novel non-planar conformation, and as a result paramagnetic chiral bis-bidentate complexes such as [FeL72(CH3CN)2]2+ are readily available. PMID- 20358134 TI - Vanadium procatalysts bearing chelating aryloxides: structure-activity trends in ethylene polymerisation. AB - High-valent vanadium complexes bearing a variety of chelating aryloxides including di- and linear tri-phenolates, C/N-capped tripods, phenoxyimines and calixarenes type ligands, when used in combination with dialkylaluminium halides as co-catalyst and a reactivator, are found to act as highly active catalytic systems for alpha-olefin polymerisation. Pro-catalyst structure-catalytic activity trends can be identified for the various ligand families employed. PMID- 20358135 TI - A robust, sensitive, and versatile HMBC experiment for rapid structure elucidation by NMR: IMPACT-HMBC. AB - A robust, versatile and easy to optimize HMBC experiment for complex organic structure elucidation which has been experimentally tested on cholesteryl acetate, cyclosporine and isopropylidene glycerol is described. The proposed experiment, IMPACT-HMBC (improved and accelerated constant-time heteronuclear multiple-bond correlation), combines sensitivity, easy experimental setup and can be recorded with short recovery times. PMID- 20358136 TI - Beliefs and attitudes about endemic dental fluorosis among adolescents in rural Brazil. AB - OBJECTIVE: To understand beliefs and attitudes about fluorosis among young people living in a rural area. METHODOLOGICAL PROCEDURES: Qualitative study consisting of semi-structured interviews with 23 adolescents with dental fluorosis, 14 teachers and three health authorities in the city of Sao Francisco, Southeastern Brazil, in 2002. Content analysis and social representation theory were applied. ANALYSIS OF RESULTS: The organoleptic characteristics of carbonates that affect groundwater (salty flavor, whitish coloration, and turbidity) associated with negative aspects of household use of this water are considered a cause of mottled enamel. Even after contact with researchers who investigated this phenomenon and helped find a solution for this condition, the local population is still unwilling to accept fluoride as the cause of the problem and does not fully agree to use water from other sources because they are afraid of the quality of water. CONCLUSIONS: Misperceptions of the causes of dental fluorosis and water treatment costs compromise the implementation of uncontaminated surface water supplies. Health education strategies are required in parallel with solutions for securing water supply in drought-ravaged areas. PMID- 20358137 TI - Klinefelter's syndrome with renal tubular acidosis: impact on height. AB - A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature. PMID- 20358138 TI - Cystojejunostomy for non-parasitic hepatic cyst with biliary communication. AB - Non-parasitic hepatic cysts containing bile are rare entities and pose a challenge in surgical management as they cannot be managed by simple de-roofing. The biliary communication to the cyst cavity should either be closed meticulously, or these cysts should be managed by an internal drainage procedure such as cystoenterostomy. We report a 17-year-old Indian girl, in which such a cyst was treated by cystojejunostomy. PMID- 20358139 TI - Deafness due to haemorrhagic labyrinthitis and a review of relapses in Streptococcus suis meningitis. AB - Deafness is a common and often permanent neurological sequel of Streptococcus (S.) suis meningitis. Suppurative labyrinthitis, rather than direct auditory nerve infection, has been found to be the site responsible for deafness. Neuroimaging is important to localise the site involved in hearing loss and to assess the feasibility of a cochlear implantation. S. suis is very sensitive to penicillin. Although a relapse of S. suis meningitis is uncommon, it can occur despite an adequate duration of appropriate antibiotic therapy. We describe a patient with S. suis meningitis, who developed permanent deafness from haemorrhagic labyrinthitis, as shown on magnetic resonance imaging. She suffered a relapse despite a seven-week course of intravenous antibiotics. A review on six cases of relapse reported in the literature shows that relapses occurred despite two to four weeks of antibiotics being administered to the patients. The clinical implications and treatment of relapse are discussed. PMID- 20358140 TI - Complicated grief in a two-and-a-half-year-old child. AB - The concept of "absence of grief" in children has been embedded in psychoanalytic literature since its beginning. The clinical phenomenon of grief in a toddler is rarely described or analysed in the psychiatric literature. Early theorists felt that grieving does not occur until adolescence due to a younger child's psychological structure, including poor object-relations development. However, data on grief reaction in preschool children has mostly been under-reported or neglected, especially since most of the studies on childhood grief have been conducted on school-age children. We present a two-and-a-half-year-old girl, whose emotional and behavioural reactions to the loss of her grandfather became a focus of clinical attention. This report shows that even toddlers can mourn for their loved ones, although the expression and process of grief differ from that of older children and may occasionally draw clinical attention. Suggestions on how to investigate this phenomenon more closely and how to avoid it in socio cultural contexts are proposed. PMID- 20358141 TI - Brown fat uptake of 18F-FDG on dual time point PET/CT imaging. AB - The aim of this report was to assess the changes in the 18F-fluorodeoxyglucose (18F-FDG) uptake of brown fats on integrated positron emission tomography/computed tomography (PET/CT) imaging. The patient presented with an enlargement of the neck lymph nodes, and was suspicious for tuberculous lymphadenitis. A whole body PET/CT imaging was performed, followed by a delayed imaging of the neck and thoracic regions. A visually increased 18F-FDG uptake was taken as a positive finding. A semi-quantitative evaluation was performed using a maximum standardised uptake value (SUVmax), with a cut-off value above 2.5. There were a number of 18F-FDG avid activity areas seen at the supraclavicular, mediastinal, paravertebral and perirenal regions. These are in keeping with the physiological 18F-FDG uptake in brown fat. The differences in SUVmax between the two images ranged from -20 percent to +20 percent. Based on our observations, dual time point imaging may not be a reliable method for assessing the 18F-FDG uptake of brown fat. PMID- 20358142 TI - Variations of the origin and branches of the external carotid artery in a human cadaver. AB - We report a unique variation in the origin and branches of both the left and right external carotid artery (ECA) found during the dissection of a human cadaver. Knowledge of the possible anatomical variations of the ECA is especially important in facio-maxillary and neck surgeries. Surgeons need to be aware of the possibility of encountering such variations, as they may lead to difficulties in differentiating between the external and internal carotid arteries, and in identifying the branches and origins. This knowledge is also important for radiologists in the image interpretation of the face and neck regions. PMID- 20358143 TI - The man with the boggy head: cranial melioidosis. AB - Melioidosis is known to cause abscesses in various organs, including the cranium, though less commonly. We present a patient with scalp abscess and subdural empyema that was visible on computed tomography of the brain. The neurosurgical drainage grew Burkholderia pseudomallei. Despite our best effort to treat the patient using parenteral antibiotics and surgical drainage, the patient did not survive. PMID- 20358144 TI - Eruptive syringoma in a patient with trisomy 21. AB - Syringomas are benign adnexal neoplasia that are classified into four main types, according to their clinical features and associations. Syringoma associated with trisomy 21 typically presents with a periorbital cutaneous involvement. We report an 18-year-old Chinese girl with trisomy 21, who presented with eruptive syringoma, an unusual generalised form involving her trunk and limbs. A histological examination was performed to confirm the diagnosis. PMID- 20358145 TI - Diagnosis and endoscopic resection of early gastric cancer. AB - The overall prognosis of gastric cancer is generally poor due to late presentation and diagnosis. When detected early, the prognosis for gastric cancer is excellent, and curative endoscopic resection may be possible, without the need for surgery. Careful endoscopic examination is important so as to avoid missed lesions. Endoscopic resection, especially with the technique of endoscopic submucosal dissection, is a viable alternative to surgery for the curative treatment of early gastric cancer, with similar long term results, as long as strict inclusion criteria are adhered to. PMID- 20358146 TI - Writing a technical note. AB - A technical note is a short article giving a brief description of a specific development, technique or procedure, or it may describe a modification of an existing technique, procedure or device applicable to medicine. The technique, procedure or device described should have practical value and should contribute to clinical diagnosis or management. It could also present a software tool, or an experimental or computational method. Technical notes are variously referred to as technical innovations or technical developments. The main criteria for publication will be the novelty of concepts involved, the validity of the technique and its potential for clinical applications. PMID- 20358147 TI - The difference in seizure incidences between young and adult rats related to lipid peroxidation after intracortical injection of ferric chloride. AB - INTRODUCTION: Clinical studies have shown that the incidence of early post traumatic seizures is higher in children than in adults. It has been proposed that iron-induced lipid peroxidation plays an important role in the development of epileptogenic foci. This study examined some of the hypothesised reasons for the difference in the incidence of early post-traumatic seizures between children and adults. METHODS: 12 young rats and 12 adult rats were randomised into four groups. Groups 1 and 2 were control groups, comprising six young rats and six adult rats, respectively, and they were administered an intracortical injection of saline. Groups 3 and 4 were injury groups, comprising six young rats and six adult rats, respectively, and they were administered an intracortical injection of FeCl3. All the rats were observed for six hours post-injection for the occurrence of seizures, and were then killed. The injected hemispheres were extirpated and tested for the malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity as indices of oxidative damage. RESULTS: Seizures were observed only in Group 3. Increased MDA levels and decreased SOD activity were observed in Group 3 (ANOVA, p-value is less than 0.001). Increased MDA levels and decreased SOD activity were significantly higher in rats with seizures (Group 3) than in those without seizures (independent t-test, p-value is less than 0.001). CONCLUSION: Different levels of lipid peroxidation induced by an intracortical ferric chloride injection may account for the different incidence rates of seizures between young and adult rats. PMID- 20358148 TI - Studies on lipid peroxidation and non-enzymatic antioxidant status as indices of oxidative stress in patients with chronic myeloid leukaemia. AB - INTRODUCTION: Chronic myeloid leukaemia (CML) is a myeloproliferative disorder of the haematopoietic cell. Free radicals can be important causative agents of a number of human diseases, including cancer and leukaemia. Thus, antioxidants, which control the oxidative stress state, represent a major line of defense for regulating the overall true state of health. The relationship between non enzymatic antioxidant status and the levels of well-known markers of oxidative stress that are measured as lipid peroxides reflects better health indices. The aim of this study was to evaluate the plasma levels of lipid peroxidation products and non-enzymatic antioxidant status as indices of oxidative stress, disease progression and early responses to chemotherapeutic agents in chronic myeloid leukaemia patients. METHODS: The study included 128 CML patients and 50 age- and gender-matched healthy control volunteers. Indices of oxidative stress were evaluated as lipid peroxidation and non-enzymatic antioxidant status using the spectrophotometric method. RESULTS: There was a significant increase in the plasma levels of lipid peroxidation products in CML patients as compared to the healthy volunteers. The plasma levels of lipid peroxidation products continued to rise significantly as the disease progressed. The non-enzymatic antioxidant status was found to be significantly decreased in CML patients as compared to the healthy participants. The plasma levels of non-enzymatic antioxidant status continued to decrease significantly during the disease progression. CONCLUSION: It can be concluded that plasma lipid peroxidation and non-enzymatic antioxidant status reflect oxidative stress in CML patients, and may be used as indices for oxidative stress, disease progression and early responses to different therapeutic modalities. PMID- 20358149 TI - The prevalence of iron deficiency anaemia in female medical students in Tehran. AB - INTRODUCTION: Female adolescents and adults are among the population groups who are most affected by iron deficiency. Thus, the aim of this study was to investigate the prevalence of iron deficiency and iron deficiency anaemia in female students aged 18 to 25 years old from the Tehran University of Medical Sciences, Iran. METHODS: 295 female university students participated in the study. The mean corpuscular volume (MCV) and haemoglobin (Hb), serum ferritin, serum iron and total iron binding capacity (TIBC) levels were measured. Iron deficiency anaemia was defined as a situation where Hb is less than 12 g/dL, MCV is less than 78 microm3, ferritin is less than 12 ng/ml or transferin saturation (TS) (iron/TIBC x 100) is less than 15 percent, Iron deficiency (ID) was defined as a situation where Hb is greater than or equal to 12 g/dL, MCV is greater than or equal to 74 microm3, ferritin is less than 12 ng/ml or TS is less than 15 percent. RESULTS: The complete data was available for 237 students. The prevalence of ID was 40.9 percent and that of IDA was 3.8 percent. Normal iron status was found in 49.8 percent of the subjects. The remaining (5.5 percent) had other kinds of anaemia or required confirmatory tests. CONCLUSION: ID is common among 18 to 25-year-old Iranian female university students. Iron supplementation is thus required for the target group. PMID- 20358150 TI - A comparison between short-interval and regular-interval follow-up for BI-RADS category 3 lesions. AB - INTRODUCTION: The aim of this study was to compare the short-interval and regular interval follow-up in women with Breast Imaging Reporting and Data System (BI RADS) category 3 screen imaging studies. The image stability, rate of image detected breast cancer and stage of cancer are studied. METHODS: Women who had BI RADS 3 screen imaging studies (mammography and ultrasonography) conducted between the period January 2003 and December 2005 were retrospectively identified using the computerised database at the Department of Radiology, Ramathibodi Hospital, Thailand. Women who had known breast cancer status at two years after screening were included in the study and divided into two groups: short-interval (six months after screening) or regular-interval (one year after screening) follow-up. The two groups were compared in terms of the baseline clinicoradiologic characteristics and outcomes, including the image stability, image-detected breast cancer and the cancer stage at detection. RESULTS: A total of 10,086 women underwent screen imaging studies within the study period. Of these, 1,541 (15 percent) were categorised as BI-RADS 3. Only 1,036 women (67 percent) had follow up images done six to 12 months after screening, and 846 (82 percent of 1,036 women) also had known cancer status two years after the screening. Breast cancer was noted in seven women (a positive predictive value of 0.7 percent). There were no significant differences between the two groups of women in terms of their baseline characteristics, image stability at the initial follow-up, the rate of image-detected breast cancer and the stage of cancer at detection. CONCLUSION: There were no significant differences in the effectiveness of short-interval versus regular-interval follow-up in women with BI-RADS 3 screen imaging studies. PMID- 20358151 TI - The prevalence of obesity among clinical students in a Malaysian medical school. AB - INTRODUCTION: This study aimed to determine the prevalence of obesity among medical students and its relationship with their dietary intake and physical activities. METHODS: This observational study was carried out on 240 medical students during the clinical phase of their medical course in a private medical school. Their body weight and height were measured, and a standardised questionnaire was used to collect information on their physical activities and dietary intake. RESULTS: The median body weight of the participants was 59.0 kg (interquartile range: 51.3-66.8), the mean body height was 166.1 cm (standard deviation [SD] 8.5 cm), and the mean body mass index (BMI) was 21.8 kg/m2 (SD 3.4 kg/m2). Based on the World Health Organization BMI cut-offs for the Asian population, 30.1 percent (n is equal to 72) of the students were overweight or obese, with a BMI that was equal to or greater than 23.0 kg/m2. Logistic regression analysis showed that, after controlling for various potential confounders, the only significant risk factors associated with overweight/obesity among these students were: male gender (adjusted odds ratio [OR] 2.1; 95 percent confidence intervals [CI] of 1.1 and 4.1; p is equal to 0.03), Malay ethnic group (adjusted OR 2.4; 95 percent CI 1.0 and 5.7; p is equal to 0.04), Indian ethnic group (adjusted OR 3.6; 95 percent CI 1.5 and 8.9; p is equal to 0.005), and the number of soft drinks consumed per week (adjusted OR 1.3; 95 percent CI 1.0 and 1.5; p is equal to 0.02). Skipping breakfast, the frequency of physical exercise per week, the number of hours of sleep per day, and eating noodles or roti canai (a type of Malaysian pancake) for breakfast were not significant risk factors. CONCLUSION: Obesity remains a common problem among medical students in their clinical years. PMID- 20358152 TI - Cytogenetic and epidemiological profiles of Down syndrome in a Moroccan population: a report of 852 cases. AB - INTRODUCTION: Trisomy 21 or Down syndrome is the most common type of autosomal chromosome abnormality, with an incidence of one out of 700 live births. Down syndrome is associated with psychomotor delay, characteristic facial features, and sometimes, cardiac, digestive and ocular malformations. The aim of this study was to estimate the proportions of various cytogenetic types of trisomy 21, and to study the link between maternal age and trisomy 21 in the Moroccan population, in order to provide data on the cytogeneticity and epidemiology of Down syndrome in Morocco. METHODS: A retrospective analysis was performed on the case records of 852 patients who were confirmed as Down syndrome by cytogenetic analysis at the Department of Medical Genetics, National Institute of Health, Morocco. RESULTS: Among the 852 cases of Down syndrome presenting over a period of 15 years, free trisomy 21 was present in 820 cases (96.24 percent). 27 patients had translocation and five cases were mosaics. The median maternal age of the Moroccan mothers at the birth of the affected child was 35.39 years. CONCLUSION: The identification of specific types of chromosomal abnormalities in Down syndrome children is important as it assists with patient management and family counselling. PMID- 20358153 TI - The risk factors for mortality in elderly patients with hip fractures: postoperative one-year results. AB - INTRODUCTION: Hip fractures in the elderly are associated with significant mortality. This study aimed to investigate the risk factors for mortality in elderly patients with hip fractures during a one-year period. METHODS: This was a prospective study which included consecutive isolated nonpathologic hip fractures in 74 (52 female, 22 male) patients in a level-1 trauma centre. These patients were 65 years or older and were ambulatory before the fracture. The patients were treated with hemiarthroplasty. The factors investigated were age, gender, nutritional status determined by blood albumin and total lymphocyte count, haemoglobin levels on the day of admission, mobilisation time after surgery, length of hospital stay, comorbidities, American Society of Anaesthesiologists (ASA) rating of operative risk, and the time period between injury and surgery. The patients were followed up for one year after surgery, or until death. RESULTS: In total, 15 patients died during the one-year period. Patient survival was 94.6 percent at 3 months, 81.1 percent at 6 months and 79.7 percent at 12 months. There were two in-hospital deaths. The factors significantly associated with mortality were patients with more than two comorbidities, an ASA score of III-IV, a blood albumin level of less than 3.5 g/dl and a total lymphocyte count of less than 1500 cells/ml on admission. However, after the multivariate analysis, an ASA score of III-IV, low total lymphocyte count, female gender and low haemoglobin levels on admission remained the independent and significant risk factors associated with a one-year mortality. CONCLUSION: This study confirms that a high ASA score, female gender, a lower lymphocyte count and low haemoglobin levels on admission are significant factors in assessing the one-year mortality in elderly patients with hip fractures. Predicting these risk factors improves the case management. PMID- 20358154 TI - Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn. AB - INTRODUCTION: The aim of this study was to compare the response and survival rates of term infants with persistent pulmonary hypertension of the newborn (PPHN) on high frequency oscillatory ventilation (HFOV) treated with either inhaled nitric oxide (iNO) or intravenous magnesium sulphate (MgSO4). METHODS: This was a randomised controlled study. The inclusion criteria were infants with respiratory distress, oxygen index equal to or greater than 25 despite HFOV support, and echocardiographic evidence of PPHN. Infants in the MgSO4 group (n is 13) were loaded with MgSO4 200 mg/kg infused over half an hour, followed by continuous infusion at 50-150 mg/kg/hour to attain a serum magnesium level of 5.0 7.0 mmol/L. Infants in the iNO group (n is 12) were administered nitric oxide at an initial concentration of 20 ppm. Analysis was done on an intention-to-treat basis. RESULTS: There was no significant difference in the median age when the vasodilators were commenced (MgSO4 group: 14.0 hours, interquartile range [IQR]: 7.5, 27.0; iNO group: 14.8 hours, IQR: 12.5, 35.3, p is 0.8). There was no significant difference in the proportion of infants who responded primarily to either vasodilator (MgSO4: 23.3%, iNO: 33.3%, p is 1.0) . After switching over to iNO following a failed MgSO4 therapy, a significantly higher proportion (9 out of 10) of the non-respondents in the MgSO4 group recovered from PPHN and survived compared to the non-respondents in the iNO group (1 out of 8) who switched over to intravenous MgSO4 (p is less than 0.03). CONCLUSION: Infants who were administered iNO following a failed MgSO4 therapy were associated with a better outcome than those who were administered MgSO4 following a failed iNO therapy. PMID- 20358155 TI - Dual blockade of the renin-angiotensin-aldosterone system is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy. AB - INTRODUCTION: Blockade of the renin-angiotensin-aldosterone system (RAAS) by either the angiotensin converting enzyme inhibitor (ACE-I) or the angiotensin II receptor blocker (ARB) has been shown to reduce albuminuria and delay the progression of diabetic nephropathy. This study evaluated the effect of dual blockade of the RAAS by adding an ACEI or an ARB to the administration of either drug alone on albuminuria in Asian type 2 diabetic patients with nephropathy. METHODS: 34 patients were randomly assigned to receive either enalapril 20 mg or losartan 100 mg once daily for eight weeks. Following this, all patients received a combination of enalapril 10 mg and losartan 50 mg daily for eight weeks, followed by enalapril 20 mg and losartan 100 mg daily for another eight weeks. The blood pressure and 24-hour urinary albumin excretion (UAE) were monitored. RESULTS: Following monotherapy with enalapril, there was a mean and standard error (SE) reduction in the UAE and mean arterial pressure (MAP) of 9.8 (SE 6.8) percent (p-value is 0.061) and 5.3 (SE 2.2) mmHg (p-value is 0.026), respectively; the reduction in UAE and MAP following monotherapy with losartan was by 10.9 (SE 14.1) percent (p-value is 0.053) and 4.5 (SE 1.9) mmHg (p-value is 0.034), respectively. Combination therapy with enalapril and losartan further reduced the UAE (11.2 [SE 8.7] percent, p-value is 0.009] despite there being no significant change in the MAP (-1.2 [SE 1.47] mmHg, p-value is 0.42). The adverse effects included dry cough (seven [19.4 percent] patients, resulting in the withdrawal of medication in two patients), and transient hyperkalaemia (two [six percent] patients). CONCLUSION: Dual blockade of the RAAS is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy. PMID- 20358156 TI - Type 2 diabetes mellitus patients with poor glycaemic control have lower quality of life scores as measured by the Short Form-36. AB - INTRODUCTION: This study aimed to compare the quality of life based on the Short Form-36 (SF-36) between two different groups of type 2 diabetes mellitus patients with glycaemic control: those with a glycosylated haemoglobin (HbA1c) level at or below 7.5 percent and those above 7.5 percent. METHODS: In this cross-sectional study, a generic SF-36 questionnaire was self-administered to patients with type 2 diabetes mellitus. Based on the HbA1c level, the mean SF-36 scale scores were compared. The analysis of covariance was used to obtain the adjusted mean scores of the SF-36 scales while controlling for age and duration of type 2 diabetes mellitus. RESULTS: 150 patients with type 2 diabetes mellitus were analysed. There were 63 (42 percent) women and 87 (58 percent) men, and their mean HbA1c level was 8.9 percent (SD 2.4 percent). When comparing the two groups of patients with different HbA1c levels, the adjusted means of four scales: physical health functioning, general health, social functioning and mental health, differed significantly between the two. The SF-36 scale scores in type 2 diabetes mellitus patients were also lower than those of the SF-36 norms for the Malaysian population. CONCLUSION: Type 2 diabetes mellitus patients with poor glycaemic control had lower mean SF-36 scores in physical functioning, general health, social functioning and mental health, and the SF-36 scores in these patients were also lower than the SF-36 norms of the Malaysian population. PMID- 20358157 TI - Iodopovidone pleurodesis: experience of a tertiary hospital in Kolkata. AB - INTRODUCTION: The management of recurrent pleural effusion or pneumothorax has always been a cause for serious concern among chest physicians. Among the wide variety of agents that are available for pleurodesis, povidone iodine is now perhaps the most sought after agent as it is cheap, easily available, effective and safe. This study was conducted to establish the efficacy and safety of povidone iodine as an agent for pleurodesis in patients with recurrent pleural effusion and pneumothorax. METHODS: A total of 38 consecutive patients with symptomatic malignant or recurrent pleural effusion and pneumothorax received povidone iodine for pleurodesis over a period of 18 months. The mean follow-up period was 10.2 months, with a standard deviation of 2.9 months. RESULTS: Out of the 38 patients, 29 had malignant pleural effusion, eight had recurrent pneumothorax and one had tubercular pleural effusion which was nonresponsive to antitubercular therapy. A complete response with no recurrence during follow-up was obtained in 34 (89.5 percent) patients. All the cases of failure had malignant pleural effusion. Three (7.9 percent) patients experienced intense chest pains after the installation of sclerosing agent, but they recovered with immediate symptomatic management. CONCLUSION: Recurrent pleural effusion or pneumothorax due to any cause may be managed effectively and safely by chemical pleurodesis with povidone iodine. It may be considered as the agent of choice to achieve pleurodesis, especially in resource constrained countries like India, as it is inexpensive and easily available. PMID- 20358158 TI - Ministry of health clinical practice guidelines: cancer screening. AB - The Ministry of Health publishes national clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with key recommendations from the guidelines) from the Ministry of Health clinical practice guidelines on cancer screening, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov. sg/mohcorp/publications.aspx?id=24018). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines. PMID- 20358160 TI - Comments on: Airway foreign bodies in children: experience of 132 cases. PMID- 20358161 TI - Ptosis due to parasitic infestation. PMID- 20358162 TI - Apolipoproteins: emerging biomarkers for CAD. PMID- 20358163 TI - Swine flu and respiratory protection. PMID- 20358164 TI - The LOOPPEG system--ready for prime time? PMID- 20358168 TI - Effect of shock wave stimulation on hypertonic plantar flexor muscles in patients with cerebral palsy: a placebo-controlled study. AB - BACKGROUND: Extracorporeal shock wave therapy has been reported to be effective in reducing muscle hypertonia in adults. AIM: To evaluate the effect of shock wave treatment of spastic muscles in children with cerebral palsy. METHODS: Twelve children with spastic equinus foot (6 boys,6 girls; mean age 8 years (standard deviation (SD) 2.31)) were monitored. Clinical (Ashworth Scale, passive range of motion) and instrumental (pedobarography) examination were performed. This is an open study with one placebo treatment session, followed 6 weeks later by one active shockwave treatment session. Gastrocnemius muscles and soleus muscles were treated. RESULTS: After placebo stimulation no clinical or instrumental effect was seen. After a single active shock wave stimulation a significant decrease in the Ashworth Scale (from 3 to 2), an increase in the range of motion (from 20 degrees to 50 degrees), and an increase in the whole plantar surface area of the treated limb (from 40.3 to 80.2 cm2) were observed in all patients. This effect lasted for 4 weeks in all patients. CONCLUSIONS: A single active shock wave stimulation produced a significant long-lasting reduction in hypertonia in the plantar flexors in children with cerebral palsy. PMID- 20358169 TI - [Intubation-linked dental injuries. Relevance of individually adaptable tooth protection models]. AB - BACKGROUND: Tooth damage during anaesthesia could be reduced by using tooth protectors during endotracheal intubation. The effectiveness of different models was investigated using an upper jaw model. METHOD: A total of 6 individual adaptable dental protectors (Endoragard and Camo, with wax or silicone filling, respectively, Beauty pink dental wax with and without tissue inserts) were examined in three different categories. The upper jaw was covered with each dental shield and then loaded with a force of 150 N via a blade of a laryngoscope. Subsequently, force reduction was measured in axial as well as horizontal directions. Furthermore, the reduction in oral view was determined by measuring the thickness of each dental shield with a micrometer. RESULTS: The combination of Camo and silicone achieved the maximum horizontal force reduction value (39.2 N). Endoragard and silicone achieved the best axial value (21.6 N). Beauty pink wax had the thinnest dental shield (2.8 mm), whereas the combination of Camo and silicone gave the most limited view inside the oral cavity (3.8 mm). CONCLUSION: Preformed dental shields are useful for reducing the force applied to the teeth and potentially reducing the probability of tooth damage during laryngoscopy. However, the shield with the highest force reduction capability is relatively large and expensive which makes general use almost impossible. The model Beauty pink was slightly less force reducing and could be considered as an inexpensive and yet effective tool for clinical assignment. PMID- 20358170 TI - [Thyroid diseases and hypertension]. AB - Thyroid hormones have several well-recognized effects on the vasculature and heart, resulting in characteristic cardiovascular changes in thyroid disease, including an increase in blood pressure. In hyperthyroidism reduced systemic vascular resistance and increased blood volume lead to an enhanced preload, which, in association with reduced afterload, improved contractility, as well as increased beta-adrenergic activity, results in isolated systolic hypertension based on enhanced stroke volume and cardiac output. In contrast, hypothyroidism causes increased systemic vascular resistance in association with decreased arterial compliance resulting in elevated diastolic blood pressure. Therefore in the evaluation of arterial hypertension secondary hypertension based on thyroid disease should always be considered, especially given the fact that blood pressure changes in the course of thyroid dysfunction are usually reversible upon adequate treatment of hypo- or hyperthyroidism. PMID- 20358171 TI - [Organ manifestations of hyperthyroidism]. AB - Patients with hyperthyroidism tend to feel well and procrastinate the visit to the doctor and hence diagnosis of the disease. Among a whole variety of more or less distinct symptoms affecting many organs, cardiovascular disease is most prevalent and serious, because it relates to an increase in mortality of patients with hyperthyroidism. Recent epidemiological studies have clearly demonstrated that the disease already begins with the subclinical states of hyperthyroidism and, as a consequence, treatment should also be commenced early on. Novel insights into the mechanisms and actions of thyroid hormones at the pathophysiological level offer a potential for the development and future therapeutic use of selective hormone analogues. Despite the high frequency and importance of thyroid disorders, awareness appears to be decreasing and over dosage of thyroid hormones in benign thyroid conditions is frequent. This review should emphasize that the thyroid gland affects the structure and function of a multitude of organs and, on the other hand, many symptoms and complaints, related to various organ systems, should raise suspicion of thyroid disease. PMID- 20358172 TI - Recruits of the stingless bee Scaptotrigona pectoralis learn food odors from the nest atmosphere. AB - The ability to learn food odors inside the nest and to associate them with food sources in the field is of essential importance for the recruitment of nestmates in social bees. We investigated odor learning by workers within the hive and the influence of these odors on their food choice in the field in the stingless bee Scaptotrigona pectoralis. During the experiments, recruited bees had to choose between two feeders, one with an odor that was present inside the nest during the recruitment process, and one with an unknown odor. In all experiments with different odor combinations (linalool/phenylacetaldehyde, geraniol/eugenol) a significant majority of bees visited the feeder with the odor they had experienced in their nest (chi (2)-tests; p < 0.05). By contrast, the bees showed no preference for one of two feeders when they were either baited with the same odor (linalool) or contained no odor. Our results clearly show that naive workers of S. pectoralis can learn the odor of a food source during the recruitment process from the nest atmosphere and that their subsequent food search in the field is influenced by the learned odor. PMID- 20358173 TI - Genetic mapping of microsatellite markers around the arcelin bruchid resistance locus in common bean. AB - The deployment in common beans (Phaseolus vulgaris L.) of arcelin-based bruchid resistance could help reduce post-harvest storage losses to the Mexican bean weevil [(Zabrotes subfasciatus (Boheman)]. Arcelin is a member of the arcelin phytohemagglutinin-alpha-amylase inhibitor (APA) family of seed proteins, which has been extensively studied but not widely used in bean breeding programs. The purpose of this study was to evaluate microsatellite markers for genetic analysis of arcelin-based bruchid resistance and to determine the orientation of markers and the rate of recombination around the APA locus. A total of 10 previously developed microsatellites and 22 newly developed markers based on a sequenced BAC from the APA locus were screened for polymorphism and of these 15 were mapped with an F(2) population of 157 individuals resulting from a susceptible x resistant cross of SEQ1006 x RAZ106 that segregated for both the arcelin 1 allele and resistance to the bruchid, Z. subfasciatus. Microsatellites derived from APA gene sequences were linked within 0.8 cM of each other and were placed relative to the rest of the b04 linkage group. In a comparison of genetic to physical distance on the BAC sequence, recombination was found to be moderate with a ratio of 125 kb/cM, but repressed within the APA locus itself. Several markers were predicted to be very effective for genetic studies or marker-assisted selection, based on their significant associations with bruchid resistance and on low adult insect emergence and positions flanking the arcelin and phytohemagglutinin genes. PMID- 20358174 TI - Symptom recognition and help seeking for depression in young adults: a vignette study. AB - PURPOSE: Many young people with psychological problems do not seek help. Recognition of problems and knowledge of appropriate sources of help may increase the likelihood of help seeking. This study aimed to explore whether young adults recognised depressive symptoms in a vignette, and how they thought a young person might respond to these symptoms. METHODS: A postal survey was sent to 3,004 young people aged 16-24 in SW England. The survey included a two-part vignette; the first part depicted mild depressive symptoms, and the second part depicted severe depressive symptoms. Open-ended questions exploring symptom recognition and illness behaviour were answered by 1,125 respondents. RESULTS: Severe depressive symptoms were recognised by 61.4% of respondents. Young men, particularly those from deprived backgrounds were less likely than women to recognise a mental health problem. Men were also less likely to suggest seeing a doctor than women. 64.7% of the respondents who recognised a mental health problem suggested seeing a doctor, however, only 16.4% thought a severely depressed person actually would see a doctor. CONCLUSIONS: Whilst the majority of young people recognised symptoms of severe depression, the gap between perceived options for help and proposed help seeking behaviour is clinically relevant. The sociodemographic groups at greatest risk of suicide are the least likely to recognise depression, highlighting a need to develop interventions targeting men, particularly those from deprived backgrounds. PMID- 20358175 TI - Role of physical and sedentary activities in the development of depressive symptoms in early adolescence. AB - OBJECTIVE: To examine whether levels of physical activity or sedentary activity are risk factors for the development of depressive symptoms in early adolescence. METHODS: A representative sample of 2,464 12- to 15-year-old adolescents living in the middle of Norway was assessed twice, during the years 1998 (T1) and 1999/2000 (T2). The attrition rate was 4.3%. We assessed depressive symptoms (using the Mood and Feelings Questionnaire, MFQ) and levels of physical and sedentary activities at baseline and follow-up. Various potentially confounding factors, including demographic factors, were assessed at baseline. RESULTS: The MFQ scores at T1 were cross-sectionally associated with low levels of vigorous exercise. A possible buffering effect of vigorous exercise on the relationship between stressful life events and depression was demonstrated. In longitudinal analysis low levels of vigorous exercise and high levels of sedentary activities (boys only) predicted a high score (MFQ >= 25) at T2. CONCLUSIONS: Low levels of vigorous exercise and high levels of sedentary activities (boys only) constituted independent risk factors for the development of a high level of depressive symptoms in a 1-year study of young adolescents. This knowledge should be considered by policy makers, preventative services, and health-care professionals. PMID- 20358176 TI - Botulinum toxin and urinary bladder disorders in women: new insight into an old problem. PMID- 20358177 TI - TVT-S for surgical treatment of stress urinary incontinence: prospective trial, 1 year follow-up. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the effectiveness of and morbidity associated with the tension-free vaginal tape secur (TVT-S) procedure in women with stress urinary incontinence (SUI). METHODS: We performed a prospective trial, examining 86 women with primary SUI. Eighty-two patients had a 1-year follow-up (dropout rate = 4.6%). The preoperative evaluation included urinalysis, urodynamic studies, and validated questionnaires. The 1-year outcome evaluation also included a 1-h pad testing. RESULTS: At the 1 year follow-up, 43 (52.4%) women were objectively cured, and 14 (17.1%) women were objectively improved. Subjectively, 49 (59.7%) patients did not experience urine loss, and 18 (22.2%) women improved in this respect. Postoperative de novo urge incontinence symptoms developed in 24.4% (n = 20) of patients. Vaginal defect healing occurred in 6.1% (n = 5) of patients, and one (1.2%) case of urethral erosion was reported. CONCLUSION: Objective and subjective cure rates following TVT-S are inferior to other tape procedures. PMID- 20358178 TI - Extracellular monoenzyme deglycosylation system of 7-O-linked flavonoid beta rutinosides and its disaccharide transglycosylation activity from Stilbella fimetaria. AB - We screened for microorganisms able to use flavonoids as a carbon source; and one isolate, nominated Stilbella fimetaria SES201, was found to possess a disaccharide-specific hydrolase. It was a cell-bound ectoenzyme that was released to the medium during conidiogenesis. The enzyme was shown to cleave the flavonoid hesperidin (hesperetin 7-O-alpha-rhamnopyranosyl-beta-glucopyranoside) into rutinose (alpha-rhamnopyranosyl-beta-glucopyranose) and hesperetin. Since only intracellular traces of monoglycosidase activities (beta-glucosidase, alpha rhamnosidase) were produced, the disaccharidase alpha-rhamnosyl-beta-glucosidase was the main system utilized by the microorganism for hesperidin hydrolysis. The enzyme was a glycoprotein with a molecular weight of 42224 Da and isoelectric point of 5.7. Even when maximum activity was found at 70 degrees C, it was active at temperatures as low as 5 degrees C, consistent with the psychrotolerant character of S. fimetaria. Substrate preference studies indicated that the enzyme exhibits high specificity toward 7-O-linked flavonoid beta-rutinosides. It did not act on flavonoid 3-O-beta-rutinoside and 7-O-beta-neohesperidosides, neither monoglycosylated substrates. In an aqueous medium, the alpha-rhamnosyl-beta glucosidase was also able to transfer rutinose to other acceptors besides water, indicating its potential as biocatalyst for organic synthesis. The monoenzyme strategy of Acremonium sp. SES201 = DSM 24697, [corrected] as well as the enzyme substrate preference for 7-O-beta-flavonoid rutinosides, is unique characteristics among the microbial flavonoid deglycosylation systems reported. PMID- 20358179 TI - Advances in molecular detection of Aspergillus: an update. AB - Filamentous cosmopolitan fungi of the genus Aspergillus can be harmful in two ways, directly they can be opportunistic pathogens causing aspergillosis and indirectly due to aflatoxin production on food products which can lead to aflatoxicosis. Therefore, a number of methods have been proposed so far for detection of the fungi with lowest possible concentration at the earliest. Molecular methods such as PCR and/or in combination with certain techniques have been found to be useful for Aspergillus detection. We discuss here various technologies that have emerged in recent years and can possibly be used for the molecular detection of Aspergillus in an efficient way. These methods like RSIC, C-probe, and inversion probe with pyrosequencing or direct ss/dsDNA detection have been used for the identification of fungal or bacterial pathogens and thus formulate a 'gold standard' for Aspergillus detection. PMID- 20358180 TI - Molecular characterization and isolation of cytochrome P450 genes from the filamentous fungus Aspergillus oryzae. AB - We explored the molecular diversity of cytochrome P450 genes in the filamentous fungus Aspergillus oryzae using bioinformatic and experimental approaches. Based on bioinformatic annotation, we found 155 putative genes of cytochromes P450 in the whole genome sequence; however, 13 of 155 appeared to be pseudogenes due to sequence deletions and/or inframe stop codon(s). There are 87 families of A. oryzae cytochromes P450 (AoCYPs), indicating considerable phylogenetic diversity. To characterize A. oryzae AoCYPs, we attempted to isolate cDNAs using RT-PCR and determined their transcriptional capabilities. To date, we have confirmed gene expression of 133 AoCYPs and cloned 121 AoCYPs as full-length cDNAs encoding a mature open reading frame. Using experimentally deduced sequences and intron-exon organization, we analyzed AoCYPs phylogenetically. We also identified intronic consensus sequences in AoCYPs genes. The experimentally validated exonic and intronic sequences will be a powerful advantage in identification and characterization of novel P450s from various ascomycetous fungi. PMID- 20358181 TI - 26-Week carcinogenicity study of di-isodecyl phthalate by dietary administration to CB6F1-rasH2 transgenic mice. AB - This study examined the carcinogenic potential of di-isodecyl phthalate (DIDP) in rasH2 mice. DIDP was administered to 15 rasH2 mice/gender/group at dietary levels of 0, 0.1, 0.33, or 1% and 15 wild-type mice/gender/group at dietary levels of 0 and 1% for 26 weeks. Non-neoplastic changes were observed in the liver (parenchymal inflammation, fatty changes, diffuse hepatocyte hypertrophy with eosinophilic granules and focal necrosis) and kidneys (tubular basophilia and tubular hyperplasia) after administration of DIDP in the rasH2 and wild-type mice. In the neoplastic lesions, there were a higher number of hepatocellular adenomas in the male rasH2 mice receiving 1% DIDP, compared with the findings in the liver of control rasH2 mice or wild-type mice. The incidence of hepatocellular adenomas in the 0.1, 0.33, and 1% DIDP exposed rasH2 mice was 7% (1/15), 7% (1/15), and 33% (5/15), respectively. This study adds a set of results for an additional test chemical for the performance of the rasH2 short-term transgenic model to the existing database of 3 compounds (WY-14643, DEHP, and clofibrate) tested in the ILSI/HESI ACT project. PMID- 20358182 TI - Suitability of ultra-high performance liquid chromatography for the determination of fat-soluble nutritional status (vitamins A, E, D, and individual carotenoids). AB - Our aim was to assess the suitability of ultra-high performance liquid chromatography (UHPLC) for the simultaneous determination of biomarkers of vitamins A (retinol, retinyl esters), E (alpha- and gamma-tocopherol), D (25-OH vitamin D), and the major carotenoids in human serum to be used in clinical practice. UHPLC analysis was performed on HSS T3 column (2.1 x 100 mm; 1.8 microm) using gradient elution and UV-VIS detection. The system allows the simultaneous determination of retinol, retinyl palmitate, 25-OH-vitamin D, alpha- and gamma-tocopherol, lutein plus zeaxanthin, alpha-carotene, beta-carotene, alpha- and beta-cryptoxanthin and lycopene. The method showed a good linearity over the physiological range with an adequate accuracy in samples from quality control programs. Suitability of the method in clinical practice was tested by analyzing samples (n = 286) from patients. In conclusion, UHPLC constitutes a reliable approach for nutrient/biomarker profiling allowing the rapid, simultaneous and low-cost determination of vitamins A, E, and D (including vitamers and ester forms) and the major carotenoids in clinical practice. PMID- 20358183 TI - X-ray diffraction microtomography (XRD-CT), a novel tool for non-invasive mapping of phase development in cement materials. AB - A recently developed synchrotron-based imaging technique, X-ray diffraction microtomography (XRD-CT), has been applied here for the first time to a complex system, the hydrating Portland cement paste, in order to monitor the evolution of microstructure and phase formation with a 3D non-invasive imaging approach. The ettringite-XRD-peak-based image reconstructions, combined with transmission microtomography (X-microCT) images, allowed to assess the ubiquitous distribution of this phase, which appears early in the hydration process and showed its preferential concentration in the relatively less compact regions of the paste. The comparison of greyscale histograms for cement pastes after 9 and 58 h from hydration showed an increase of ettringite content with age, in agreement with the quantitative Rietveld analysis of the sum patterns. By renormalizing the greyscale histograms to the relative weight fraction, as obtained from Rietveld refinements, a new technique which allows estimation of phase contents with spatial resolution has been developed. The results achievable by combining XRD CT, X-microCT and Rietveld appear very promising to provide experimental snapshots of the cement hydration process to be compared with results obtained from computer simulations. PMID- 20358184 TI - Layer-by-layer assembly of small interfering RNA and poly(ethyleneimine) for substrate-mediated electroporation with high efficiency. AB - Electroporation microarrays have been developed for the high-throughput transfection of expression constructs and small interfering RNAs (siRNAs) into living mammalian cells. These techniques have potential to provide a platform for the cell-based analysis of gene functions. One of the key issues associated with microarray technology is the efficiency of transfection. The capability of attaining reasonably high transfection efficiency is the basis for obtaining functional data without false negatives. In this study, we aimed at improving the transfection efficiency in the system that siRNA loaded on an electrode is electroporated into cells cultured directly on the electrode. The strategy we adopted here is to increase the surface density of siRNA loaded onto electrodes. For this purpose, the layer-by-layer assembly of siRNA and cationic polymers, branched or linear form of poly(ethyleneimine), was performed. The multilayer thus obtained was characterized by infrared reflection-adsorption spectroscopy and surface plasmon resonance analysis. Transfection efficiency was evaluated in a system that siRNA specific for enhanced green fluorescent protein (EGFP) was electroporated on the electrode into human embryonic kidney cells stably transformed with the EGFP gene. The suppression of EGFP expression was assessed by fluorescence microscopy and flow cytometry. Our data showed that the layer-by layer assembly of siRNA with branched poly(ethyleneimine) facilitated to increase the surface density of loaded siRNA. As a result, the expression of EGFP gene in the electroporated cells was suppressed much more on the electrodes with the multilayer of siRNA than that with the monolayer. PMID- 20358185 TI - Monitoring the large-scale production of the antihypertensive peptides RYLGY and AYFYPEL by HPLC-MS. AB - This work reports the quantitative analysis of two novel antihypertensive peptides alpha(s1)-CN f(90-94), with sequence RYLGY, and alpha(s1)-CN f(143-149), with sequence AYFYPEL, by high-performance liquid chromatography-mass spectrometry in food-grade hydrolysates of milk proteins. The method was validated and showed sufficient specificity, reproducibility, linearity and recovery. Linear calibrations of the molecular ions m/z 671.2 and 902.3 were selected for the determination of the peptides RYLGY and AYFYPEL, respectively, and showed good statistical results (R(2) > or = 0.995 and with no significant lack-of-fit). The simplicity of RP-HPLC-MS method allowed the automated quantification of both antihypertensive peptides without any sample pretreatment. The application of this method permitted the evaluation of some hydrolysis variables, i.e., substrate, temperature, hydrolysis time or enzyme/substrate ratio, on the formation of antihypertensive peptides. The quantitative analysis of RYLGY and AYFYPEL showed that ultrafiltration was not effective to improve the content in active peptides, containing the hydrolysates and their respective permeates similar peptide amounts. PMID- 20358186 TI - Analysis of polychromaticity effects in X-ray Talbot interferometer. AB - The influence of polychromaticity of the X-ray source on the performance of an X ray Talbot interferometer applied for phase-contrast imaging is analyzed through numerical simulations based on the Fresnel diffraction theory. The presented simulation results show that the visibility of the self-image is fairly insensitive to the source polychromaticity and explain why the interferometer could be well combined with polychromatic X-ray sources in recent experiments. Furthermore, the self-image with a high visibility can be obtained under polychromatic illumination even at a high-order fractional Talbot distance. This fact implies that the acquired image quality for phase measurements can be improved, since the primary signal for phase measurement is proportional to the inter-grating distance. Finally, we mention that the results are also valid for Talbot-Lau interferometer and scanning double-grating configuration. PMID- 20358187 TI - Biomimetic chromatographic analysis of selenium species: application for the estimation of their pharmacokinetic properties. AB - The retention behavior of selenites, selenates, seleno-DL-methionine, selenocystine, selenocystamine, selenourea, dimethyl selenide, and dimethyl diselenide was investigated by means of biomimetic liquid chromatography. For this purpose, two immobilized artificial membrane (IAM) columns, namely, IAM.PC.DD2 and IAM.PC.MG, and two immobilized plasma protein columns, human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) columns, were employed using different mobile phase conditions in respect to pH and buffer composition. In general, satisfactory interrelations between retention factors obtained with the two IAM stationary phases and HSA/AGP columns were obtained. Large differences were observed between biomimetic retention factors and octanol-water logD values, since the latter fail to describe electrostatic interactions. In contrast, despite the column diversity, the net retention outcome on all four biomimetic columns was quite similar, especially in the presence of phosphate-buffered saline, which by its effective shielding alleviates the differences between the stationary phases. Of the two IAM columns, IAM.PC.DD2 showed better performance when compared with HSA and AGP columns as well as to octanol-water partitioning. Biomimetic chromatographic indices were further used to estimate the percentage of human oral absorption and plasma protein binding of the eight selenium species investigated, according to equations previously reported in the literature. The estimated values of human oral absorption imply moderate absorption only for dimethyl diselenide, which also may exhibit considerable plasma protein binding. Moderate affinity for plasma proteins should also be expected for dimethyl selenide and selenocystamine. PMID- 20358188 TI - Muscle activity differs with load compliance during fatiguing contractions with the knee extensor muscles. AB - The purpose of this study was to determine the influence of load compliance on the time to failure and rate of change in electromyographic (EMG) activity when the knee extensor muscles performed fatiguing contractions against submaximal loads. The low-compliance condition required the subject to exert a force against a rigid restraint (force control), whereas the high-compliance condition involved maintaining the knee joint angle while supporting an equivalent inertial load (position control). Both contractions were sustained for as long as possible. Each subject exerted a similar net torque about the knee joint during the force and position tasks; the target force corresponded to a force at the ankle equal to 20% of the maximal voluntary contraction (MVC) force. Thirteen healthy adults (25 +/- 7 year) participated in the study. MVC forces before the force and position tasks were similar (189 +/- 40 N vs. 179 +/- 43 N, P = 0.4), and the target force was 36 +/- 8 N. The time to task failure was longer for the force task (224 +/- 114 s) than for the position task (110 +/- 36 s, P < 0.05), but MVC force declined to a similar level immediately after task failure for the two tasks (-31 +/- 16%). The briefer time to failure for the position task was accompanied by greater rates of increase in agonist EMG amplitude and the pressor response. Coactivation ratios, in contrast, were similar for the two tasks and did not contribute to task differences in time to failure. These findings indicate that it was more difficult to sustain a submaximal contraction with the knee extensor muscles when the task required position control, despite comparable net muscle torques for the low- and high-compliance tasks. PMID- 20358189 TI - Serum concentrations of paliperidone versus risperidone and clinical effects. AB - PURPOSE: The major aim of this multicenter retrospective analysis was to examine the relationship between paliperidone serum concentrations and clinical effects in patients treated with this new antipsychotic drug. Intra-individual variability in trough serum concentrations was also analyzed in patients under treatment with either the paliperidone-extended release (ER) formulation or the risperidone immediate-release formulation. METHODS: Data were obtained from 217 patients of four medical centers who were being followed by therapeutic drug monitoring (TDM). Serum concentrations were associated with clinical response using Clinical Global Impressions (CGI) scores. RESULTS: The mean concentration of paliperidone was 36 +/- 25 ng/ml, and the mean dose corrected concentration (C/D) was 4.7 +/- 2.9 ng/ml/mg. Among patients receiving paliperidone as antipsychotic monotherapy and who showed at least a much improved level according to the CGI scores, the 25th-75th percentiles of paliperidone concentrations were 20-52 ng/ml; these were very similar to the recommended therapeutic range of 20 60 ng/ml for risperidone plus 9-hydroxy-risperidone (active moiety). In 13 patients treated with paliperidone ER and 17 patients treated with risperidone, all of whom had repeated drug measurements, the intra- and inter-individual variabilities of trough serum concentrations were similar for the paliperidone and risperidone active moiety, ranging between 30 and 35%. CONCLUSION: Based on these results, we conclude that risperidone and paliperidone have a similar therapeutic range and similar intra-individual variability in terms of trough serum levels. For treatment optimization, monitoring of plasma concentrations may be as useful for paliperidone as for risperidone. PMID- 20358191 TI - Role of lactose on the production of D-arabitol by Kluyveromyces lactis grown on lactose. AB - There are remarkably few reports on D-arabitol production from lactose. Previous studies in our laboratory have shown that the osmophilic yeast Kluyveromyces lactis NBRC 1903 convert lactose to extracellular D-arabitol. The present study was undertaken to determine the participation of osmotic stress caused by lactose on D-arabitol production by K. lactis NBRC 1903 and to provide the information on the kinetics of D-arabitol production from lactose by K. lactis NBRC 1903. It was confirmed that D-arabitol production was triggered when an initial lactose concentration was above 278 mmol L(-1). D-Arabitol yield increased with an increase in initial lactose concentration. The highest D-arabitol concentration of 79.5 mmol L(-1) was achieved in the cultivation of K. lactis NBRC 1903 in a medium containing 555 mmol L(-1) lactose and 40 g L(-1) yeast extract. Lactose was found to play two important roles in D-arabitol production by K. lactis NBRC 1903 grown on lactose. First, lactose was assimilated as the substrate both for cell growth and D-arabitol production. Second, a high lactose concentration induced cellular response to high osmotic stress and up-regulated the flow from D glucose-6-phosphate to D-arabitol. The arrest of cell growth triggered D-arabitol production. PMID- 20358192 TI - A review: recent advances and future prospects of taxol-producing endophytic fungi. AB - In the urgent search for more effective ways to treat cancer, new extraction methods of taxol from endophytic fungus have demonstrated high potential in increasing the efficiency of taxol extraction for more efficient and sustainable production of taxol and cancer treatment products. This paper summarizes recent advances in taxol-producing endophytic fungi, both in China and abroad, in the following areas: isolation and identification of endophytic fungi types, extraction and detection methods of endophytic taxol in plants, and improved efficiency of the extraction process. With the advancement of science and technology, new techniques in biotechnology, such as fungal strain improvement and recombining technique and microbial fermentation engineering, have increased the extraction yield from taxol-producing fungi, thereby improved the overall efficiency of taxol production. PMID- 20358193 TI - Molecular cloning and characterization of a novel metagenome-derived multicopper oxidase with alkaline laccase activity and highly soluble expression. AB - Lac591, a gene encoding a novel multicopper oxidase with laccase activity, was identified through activity-based functional screening of a metagenomic library from mangrove soil. Sequence analysis revealed that lac591 encodes a protein of 500 amino acids with a predicted molecular mass of 57.4 kDa. Lac591 was overexpressed heterologously as soluble active enzyme in Escherichia coli and purified, giving rise to 380 mg of purified enzyme from 1 l induced culture, which is the highest expression report for bacterial laccase genes so far. Furthermore, the recombinant enzyme demonstrated activity toward classical laccase substrates syringaldazine (SGZ), guaiacol, and 2, 6-dimethoxyphenol (2, 6 DMP). The purified Lac591 exhibited maximal activity at 55 degrees C and pH 7.5 with guaiacol as substrate and was found to be stable in the pH range of 7.0 10.0. The substrate specificity on different substrates was studied with the purified enzyme, and the optimal substrates were in the order of 2, 6-DMP > catechol > alpha-naphthol > guaiacol > SGZ > 2,2'-azino-bis(3-ethylbenzthiazoline 6-sulfonic acid). The alkaline activity and highly soluble expression of Lac591 make it a good candidate of laccases in industrial applications for which classical laccases are unsuitable, such as biobleaching of paper pulp and dyestuffs processing. PMID- 20358195 TI - Key role of nuclear medicine in seeking biomarkers of Huntington's disease. PMID- 20358196 TI - Approaches to quantify radioligands that wash out slowly from target organs. PMID- 20358197 TI - Regional lymph node involvement in T1 papillary thyroid carcinoma: a bicentric prospective SPECT/CT study. AB - PURPOSE: Hybrid imaging combining single photon emission computed tomography (SPECT) with (131)I and X-ray computed tomography (CT) performed at radioablation (RA) for thyroid carcinoma more accurately detects regional lymph node metastases (LNM) than does planar imaging. In this bicentric prospective study we used hybrid imaging in conjunction with histopathological examination to measure LNM frequency in a consecutive group of patients referred for RA due to stage T1 papillary thyroid carcinoma (PTC). METHODS: At the Departments of Nuclear Medicine of the Ludwig Maximilian University of Munich and the Friedrich Alexander University of Erlangen-Nuremberg SPECT/spiral CT is routinely performed in all PTC subjects at the time of RA. Screening of our SPECT/CT databases for PTC patients with T1 histology produced 98 patients from Munich and 53 patients from Erlangen, including 96 of 151 patients with microcarcinoma. In 69 patients of the entire group, cervical lymph node dissection had been performed, whereas nodal staging in the remaining 82 subjects was based on SPECT/CT. RESULTS: LNM incidence in the whole group was 26% [95% confidence interval (CI): 20-33%] versus 22% (95% CI: 15-31%) in the microcarcinoma subgroup. SPECT/CT was more accurate in 24.5% of our patients than planar imaging with regard to nodal staging. CONCLUSION: LNM occurs in one quarter of all patients with T1 PTC, and also in the subset with microcarcinoma. Performing (131)I SPECT/CT, either with therapeutic or diagnostic radioactivities, directly after thyroidectomy should provide more accurate staging of T1 PTC, thus facilitating optimal therapeutic management. PMID- 20358198 TI - Impacts of adjacent land use and isolation on marsh bird communities. AB - Over the next half century the human population is expected to grow rapidly, resulting in the conversion of rural areas into cities. Wetlands in these regions are therefore under threat, even though they have important ecosystem services and functions. Many obligate marsh-nesting birds in North America have shown declines over the past 40 years, and it is important to evaluate marsh bird community response to increased urbanization. We surveyed 20 coastal marshes in southern Ontario, Canada, and found that obligate marsh-nesting birds preferred rural over urban wetlands, generalist marsh-nesting birds showed no preference, while synanthropic species showed a trend towards increased richness and abundance in urban marshes. The Index of Marsh Bird Community Integrity (IMBCI) was calculated for each wetland and we found significantly higher scores in rural compared to urban wetlands. The presence of a forested buffer surrounding the marsh was not an important factor in predicting the distribution of generalists, obligates, synanthropic species, or the IMBCI. More isolated marshes had a lower species richness of obligate marsh-nesters and a lower IMBCI than less isolated marshes. Based on our results, we recommend that urban land use is not the dominant land use within 1000 m from any wetland, as it negatively affects the abundance and richness of obligate marsh-nesters, and the overall integrity of the avian community. We also recommend that all existing wetlands be conserved to mitigate against isolation effects and to preserve biodiversity. PMID- 20358199 TI - Anatomical landmarks for localizing the buccal branch of the trigeminal nerve on the face. AB - The current literature is lacking in anatomical landmarks for identifying the buccal branch of the trigeminal nerve on the face. The current study was performed to elucidate this anatomy. Forty cadaveric sides underwent dissection to measure the distances from landmarks of the superficial face to the buccal nerve in this region. On average, the buccal nerve was found to lie 3 cm lateral to the angle of the mouth and at this same level, the nerve was located a mean of 5 mm medial to the medial aspect of the masseter muscle. The buccal nerve was found to be on average 7 mm from the point of entrance of the parotid duct into the buccinator muscle and had an average distance of 5.5 mm from the facial artery. We believe that additional landmarks for identifying the buccal nerve on the face may be of use to the surgeon and dentist. PMID- 20358201 TI - Oral tranexamic acid as a novel treatment option for persistent haematuria in patients with sickle cell disease. PMID- 20358202 TI - Etanercept treatment in patients with rheumatoid arthritis on dialysis. PMID- 20358200 TI - Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia. AB - The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life. PMID- 20358203 TI - Assessment of latent tuberculosis infection in Takayasu arteritis with tuberculin skin test and Quantiferon-TB Gold test. AB - A possible relationship between Takayasu arteritis (TA) and tuberculosis (TB) has been suggested. An increased frequency of tuberculin skin test (TST) was observed in TA patients. Quantiferon-TB Gold test (QFT) is a new in vitro assay measuring interferon-gamma response to M. tuberculosis antigens and helpful in diagnosing latent TB infection. The aim of this study was to investigate latent TB infection among TA patients by the use of both TST and QFT Gold test. Ninety-four (male/female: 7/87) TA patients fulfilling ACR 1990 TA criteria from three different university hospitals in Turkey and 107 control subjects without inflammatory diseases were included in the study. Data about medical history (TA and TB) were collected for both groups. TST and QFT were performed. TST values > or =5 mm for TA patients and > or =15 mm for controls was accepted as TST positivity. Even though TA group was older (40 +/- 12 vs. 32 +/- 8, P < 0.001), there was no significant difference between TA patients and controls regarding demographic characteristics. Six TA patients and one control had a history of previous TB infection (P = 0.054). Although TST positivity was higher in TA group [55 patients (62.5%) vs. 24 controls (41.4%), P = 0.008], QFT positivity was similar between two groups [21 patients (22.3%) vs. 24 controls (22.4%), P > 0.05]. QFT was negative in two of six TA patients with previous TB history. Rate of latent TB infection in TA patients measured with QFT is no more than controls. QFT seems to be a good and favorable test compared with TST in detecting LTBI in TA. PMID- 20358204 TI - Fibromyalgia and nutrition, what do we know? AB - Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships. PMID- 20358205 TI - Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus. AB - To assess whether the CYP2C19 polymorphism modified the effect of cyclophosphamide on ovarian toxicity in Thai patients with SLE. We performed a case-control study of female patients with SLE who were treated with cyclophosphamide at Ramathibodi Hospital, Bangkok, Thailand. Cases were patient who had ovarian toxicity (sustained amenorrhoea >12 months or lack of menstruation for >4 months). CYP2C19 polymorphism was genotyped using PCR-RFLP method. Logistic regression was applied to assess CYP2C19 polymorphism as an effect modifier of cyclophosphamide. Seventy-one patients with SLE were enrolled, of which 36 (59.7%) had ovarian toxicity. CYP2C19*2 allele frequencies were 27.8 and 21.4% in the ovarian and non-ovarian toxicity groups. Patients with CYP2C19*1/*1 genotype and higher cumulative dose of cyclophosphamide (>23.75 g) had the highest odds of ovarian toxicity, i.e. 11.0 (95% CI: 1.2-99.1) times higher than patients with the CYP2C19*1/*2 or *2/*2 genotypes who received less cyclophosphamide (<23.75 g). After adjusting for age at start of treatment, this risk increased to 13.6 (95% CI: 1.1-162.2). Our results suggest that a cumulative cyclophosphamide dose of 23.75 g or higher carries a twofold higher risk of ovarian toxicity and the CYP2C19*1/*1 genotype increases the risk of toxicity a further fivefold. PMID- 20358206 TI - Can fibromyalgia be associated with whiplash injury? A 3-year follow-up study. AB - The objective of this study is to assess the long-term outcome and natural history of a cohort of patients with whiplash injury regarding the development of fibromyalgia. Of the 153 patients who were admitted to the emergency room after whiplash injury in 2004, 126 were reassessed 3 years later. Also, 33 of 53 patients from the original control group of hospitalized patients with fractures were reevaluated. Patients were interviewed by phone and by written forms using a detailed questionnaire. Patients who complained of musculoskeletal symptoms were invited and examined. The study group included 68 men and 58 women, with a mean age of 50.1 +/- 9.7. The control group included 19 men and 14 women with a mean age of 44.2 +/- 10.3. Follow-up period did not differ significantly between the groups 38.3 +/- 2.3 vs. 36.4 +/- 4.2 months. At the end of the follow-up period, three patients in the study group compared with one patient in the control group were diagnosed as having fibromyalgia; all of them were women. The rate of new onset widespread pain increased with time in both groups. Symptoms of dizziness, headaches, fatigue and sleep disturbances improved, as well as the quality of life (QOL) and the Fibromyalgia Impact Questionnaire (FIQ) scores. Insurance claims continued to be more prevalent in the control group. The results of this extended follow-up study confirm previous short-term results showing that whiplash injury and road accident trauma are not associated with an increased risk of fibromyalgia. PMID- 20358207 TI - Psychological correlates of child and adolescents with familial Mediterranean fever. PMID- 20358209 TI - Clinical impact of intraoperative frozen sections during nerve-sparing radical prostatectomy. AB - PURPOSE: Enhanced surgical techniques and standardised selection criteria have led to a higher rate of nerve-sparing (NS) radical prostatectomy (RP) procedures. The aim of this study was to evaluate the clinical value of intraoperative frozen sections (IFS) during nerve-sparing radical prostatectomy (NSRP). MATERIALS AND METHODS: Thousand and eighty-three patients with localised prostatic carcinoma were treated using retropubic RP (from 2004 to 2006). Two hundred and eighty seven of the 1083 documented cases received NS. One hundred and thirty procedures were carried out with IFS from the area of the neurovascular bundles and 157 without IFS. The decision to use IFS was made intraoperatively and based on clinical suspicion of possible positive resection margins in the area of the bundles. RESULTS: In the NS group with IFS, the results revealed positive margins in nine (6.9%) out of 130 cases, resulting in subsequent resection of the ipsilateral neurovascular bundle. The final histological report on this group revealed four additional patients (3.1%) with positive margins, but only one (0.7%) in the area of the previous neurovascular bundle. The final histopathologic reports on the 157 NS cases without IFS showed that the positive margin was in the area of the previous neurovascular bundle in only one (0.6%) of the nine cases with positive margins (5.7%). CONCLUSION: According to our data, there is no need for routine IFS during NSRP. The negative predictive value for infiltration of the NVB is high, and IFS can be dispensed with. Intraoperative biopsies should be taken in those cases where the surgeon is in doubt about the resection margins in the area of bundles. PMID- 20358210 TI - Posterior sagittal approach for mesh rectopexy as a management of complete rectal in adults. AB - OBJECTIVES: The aim of this study was to evaluate prospectively the functional outcome of posterior sagittal rectopexy with prolene mesh for rectal prolapse in young adults. PATIENTS AND METHODS: The study was carried out on 32 patients, 21 were males (65.63%) presented with complete rectal prolapse with a mean age of 36.7 +/- (range, 28-45) years. All patients were subjected to preoperative colonoscopy, clinical assessment, and anorectal manometry, dynamic magnetic resonance defecography before and after posterior sagittal rectopexy with prolene mesh. Anal incontinence and constipation were evaluated using a Wexner scale and Cleveland clinic constipation score, respectively. The patients were followed for a mean of 18.7 +/- 6.4 months. RESULTS: Fecal incontinence score recovered from 11.1 +/- 4.3 to 4.38 +/- 6.7, and constipation was improved in 13 out of 15 cases (86.57%). Straining anorectal angle (S-ARA) by MRI defecography improved from 127.2 +/- 5.9 degrees of 93.5 +/- 4.5 degrees (P < 0.05), perineal descent (PD) improved from 15.9 +/- 3.1 cm to 7.3 +/- 1.5 cm (P < 0.05). Maximal resting pressure (MRP) increased from 19.8 +/- 4.7 cm H(2)O to 43.5 +/- 3.9 cm H(2)O (P < 0.05). No mortality occurred, single case of recurrence of prolapse (3.22%), mucosal prolapse in two patients (6.44%), and mild wound infection in three patients (9.38%). CONCLUSION: These findings indicate that posterior sagittal rectopexy with prolene mesh in adults with rectal prolapse is an effective technique, with excellent functional results and without major morbidities, but still long-term results are awaited. PMID- 20358211 TI - Uterine compression suture may be useful not only for hemostasis in postpartum hemorrhage but also for prophylaxis of acute recurrence of uterine inversion. AB - Uterine compression suture is a safe and effective technique for hemostasis in postpartum hemorrhage. This technique was useful for the prophylaxis of acute recurrence of uterine inversion, which was repositioned under laparotomy. We add a new compression suture to the list of those introduced by earlier researchers. PMID- 20358212 TI - Polycythemia vera and pregnancy: experience of four pregnancies in a single patient. AB - INTRODUCTION: The association of polycythemia vera (PV) and pregnancy is rare. The estimated incidence ranges from 0.04 per 100,000 in women aged 20-34 years to 0.25 per 100,000 in those aged 35-39 years. The management of pregnant patient with PV may be problematic; less than 50 pregnancies have been reported so far in PV. MATERIAL AND METHODS: We hereby describe four pregnancies in a woman where PV was diagnosed in the fourth pregnancy. Aspirin and phlebotomy were used to maintain cell count in normal range and to avoid thrombotic complications. CONCLUSION: Pregnancy in PV appears to be associated with significantly better outcome with tailor-made management for achieving good hematocrit control, low dose aspirin and good maternal and fetal surveillance. PMID- 20358213 TI - Critical appraisal regarding the effect on reproductive outcome of hysteroscopic metroplasty in patients with recurrent miscarriage. PMID- 20358214 TI - Detection of age-related duplications in mtDNA from human muscles and bones. AB - Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification. PMID- 20358215 TI - Neuromuscular manifestations in hereditary haemochromatosis. AB - Involvement of peripheral nerves and skeletal muscles has been reported in the course of hereditary haemochromatosis (HH) but a systematic study is lacking. However, patients with HH report symptoms suggesting a possible polyneuropathy or myopathy. In this study patients with DNA proven HH were recruited from a large general teaching hospital. First, all patients were clinically examined using a structured interview and neurological exam. After reviewing these data an expert panel reached consensus about the presence of a possible neuropathy or myopathy and made recommendations for ancillary investigations (nerve conduction studies, electromyography, thermal threshold tests, laboratory tests). After a second meeting consensus was reached about the final diagnosis. Patients who had a neuropathy or myopathy of which the origin was still unclear were referred to an independent neurologist for further evaluation. Ultimately, of 46 patients included, 25 had no myopathy or neuropathy, 5 an axonal sensory motor polyneuropathy of which the cause was found (diabetes in 2, combination of diabetes and chemotherapy in 1, Charcot Marie Tooth type 2 in 1, Morbus Sjogren in 1), 9 an idiopathic axonal sensory motor polyneuropathy, 3 an idiopathic small fiber polyneuropathy and 4 a carpal tunnel syndrome. There were no cases of proven myopathy. We conclude that an idiopathic polyneuropathy was diagnosed in a relative large number of patients with HH (26%), but the causal relationship needs to be confirmed in larger (case-control) series. PMID- 20358216 TI - Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. AB - Lower limb spasticity in post-stroke patients can impair ambulation and reduces activities of daily living (ADL) performance of patients. Botulinum toxin type A (BoNTA) has been shown effective for upper limb spasticity. This study assesses the treatment of lower limb spasticity in a large placebo-controlled clinical trial. In this multicenter, randomized, double-blind, parallel-group, placebo controlled study, we evaluate the efficacy and safety of one-time injections of botulinum toxin type A (BoNTA) in Japanese patients with post-stroke lower limb spasticity. One hundred twenty patients with lower limb spasticity were randomized to a single treatment with BoNTA 300 U or placebo. The tone of the ankle flexor was assessed at baseline and through 12 weeks using the Modified Ashworth Scale (MAS). Gait pattern and speed of gait were also assessed. The primary endpoint was area under the curve (AUC) of the change from baseline in the MAS ankle score. Significant improvement in spasticity with BoNTA 300 U was demonstrated by a mean difference in the AUC of the change from baseline in the MAS ankle score between the BoNTA and placebo groups (-3.428; 95% CIs, -5.841 to 1.016; p = 0.006; t test). A significantly greater decrease from baseline in the MAS ankle score was noted at weeks 4, 6 and 8 in the BoNTA group compared to the placebo group (p < 0.001). Significant improvement in the Clinicians Global Impression was noted by the investigator at weeks 4, 6 and 8 (p = 0.016-0.048, Wilcoxon test), but not by the patient or physical/occupational therapist. Assessments of gait pattern using the Physician's Rating Scale and speed of gait revealed no significant treatment differences but showed a tendency towards improvement with BoNTA. No marked difference was noted in the frequency of treatment-related adverse events between BoNTA and placebo groups. This was the first large-scale trial to indicate that BoNTA significantly reduced spasticity in lower limb muscles. PMID- 20358217 TI - Autoradiographic study on the regenerative capability of the epithelium lining the center of the cornea after multiple debridements of its peripheral region. AB - BACKGROUND: The epithelium lining the center of the cornea is assumed to lack stem cells.The purpose is to investigate by autoradiography the regenerative capability of the epithelium lining the central region of the rabbit cornea following seven scrapings of its peripheral lining, during several months. METHODS: After marking the center of the cornea with a 6 mm-diameter trephine, the epithelium outside this area was scraped until reaching the corneoscleral zone. This procedure was repeated seven times on the same eye at intervals of 20 days. One day after the last scraping, (3)H-thymidine was injected intravitreally and the corneas processed for autoradiography. RESULTS: At 2 days after injection, the corneal surface was entirely lined by an epithelium made up by two layers of squamous cells, most of them being labeled with the DNA precursor. A multilayered epithelium was visualized at the center with most of its basal cells also labeled. The limbal epithelium had at least two of its layers labeled with the precursor. At 9 days, the multilayered central unscraped epithelium exhibited labeled cells not only in the basal but also in its suprabasal layers. The labeling index (labeled nuclei/100 cells) for its basal stratum was very close to 100%. A similar feature was observed at 16 days, except that the mutilayered central epithelium was seen lining a larger area when compared to the precedent interval and that it exhibited evidences for vertical renewal. CONCLUSIONS: The epithelium lining the central region of the cornea--where it was assumed that stem cells do not exist--exhibited capability for regeneration and self-renewal in spite of seven consecutive debridements of its periphery. No evidence was found for transposition of limbal epithelial cells to the center of the cornea during the early merger of the epithelial sliding fronts. PMID- 20358218 TI - Neural and muscular adjustments following repeated running sprints. AB - This study aimed to reveal the neural and muscular adjustments following a repeated-sprint (RS) running exercise. Sixteen subjects performed a series of neuromuscular tests before, immediately after and 30 min (passive recovery) post RS exercise (12 x 40 m sprints interspaced by 30 s of passive recovery). Sprint times significantly lengthened over repetitions (+17% from the first to the last sprint; P < 0.05). After RS running exercise, maximal voluntary contraction torque of the plantar flexors (-11 +/- 7.3%), muscle activation (twitch interpolation) (-2.7 +/- 3.4%) and soleus maximal M-wave amplitude (-20 +/- 17%) were significantly (P < 0.05) reduced but returned close to baseline after 30 min. Both soleus EMG activity and maximal Hoffmann reflex normalized with respect to M-wave amplitude did not change during the whole experiment. From pre- to post RS exercise, evoked twitch response was characterized by lower peak torque and maximal rate of torque development (-13 and -11%, respectively, P < 0.05), but was not different from baseline after recovery. Peak tetanus at 20 and 80 Hz were 17 and 8% lower (P < 0.05) in the fatigued state, respectively. Acute muscle fatigue induced by RS running exercise is mainly peripheral as the short-term (30 min) recovery pattern of plantar flexors contractile properties follows that of the voluntary force-generating capacity. PMID- 20358219 TI - Differences in whole-body fat oxidation kinetics between cycling and running. AB - This study aimed to quantitatively describe and compare whole-body fat oxidation kinetics in cycling and running using a sinusoidal mathematical model (SIN). Thirteen moderately trained individuals (7 men and 6 women) performed two graded exercise tests, with 3-min stages and 1 km h(-1) (or 20 W) increment, on a treadmill and on a cycle ergometer. Fat oxidation rates were determined using indirect calorimetry and plotted as a function of exercise intensity. The SIN model, which includes three independent variables (dilatation, symmetry and translation) that account for main quantitative characteristics of kinetics, provided a mathematical description of fat oxidation kinetics and allowed for determination of the intensity (Fat(max)) that elicits maximal fat oxidation (MFO). While the mean fat oxidation kinetics in cycling formed a symmetric parabolic curve, the mean kinetics during running was characterized by a greater dilatation (i.e., widening of the curve, P < 0.001) and a rightward asymmetry (i.e., shift of the peak of the curve to higher intensities, P = 0.01). Fat(max) was significantly higher in running compared with cycling (P < 0.001), whereas MFO was not significantly different between modes of exercise (P = 0.36). This study showed that the whole-body fat oxidation kinetics during running was characterized by a greater dilatation and a rightward asymmetry compared with cycling. The greater dilatation may be mainly related to the larger muscle mass involved in running while the rightward asymmetry may be induced by the specific type of muscle contraction. PMID- 20358220 TI - Reflexes and preflexes: on the role of sensory feedback on rhythmic patterns in insect locomotion. AB - Neuromuscular systems are stabilized and controlled by both feedforward and feedback signals. Feedforward pathways driven by central pattern generators (CPGs), in conjunction with preflexive mechanical reaction forces and nonlinear muscle properties, can produce stable stereotypical gaits. Feedback is nonetheless present in both slow and rapid running, and preflexive mechanisms can join with neural reflexes originating in proprioceptive sensors to yield robust behavior in uncertain environments. Here, we develop a single degree-of-freedom neuromechanical model representing a joint actuated by an agonist/antagonist muscle pair driven by motoneurons and a CPG in a periodic rhythm characteristic of locomotion. We consider two characteristic feedback modes: phasic and tonic. The former encodes states such as position in the timing of individual spikes, while the latter can transmit graded measures of force and other continuous variables as spike rates. We use results from phase reduction and averaging theory to predict phase relationships between CPG and motoneurons in the presence of feedback and compare them with simulations of the neuromechanical model, showing that both phasic and tonic feedback can shift motoneuronal timing and thereby affect joint motions. We find that phase changes in neural activation can cooperate with preflexive displacement and velocity effects on muscle force to compensate for externally applied forces, and that these effects qualitatively match experimental observations in the cockroach. PMID- 20358221 TI - Protein phosphatases type 2A mediate tuberization signaling in Solanum tuberosum L. leaves. AB - Tuber formation in potato (Solanum tuberosum L.) is regulated by hormonal and environmental signals that are thought to be integrated in the leaves. The molecular mechanisms that mediate the responses to tuberization-related signals in leaves remain largely unknown. In this study we analyzed the roles of protein phosphatase type 2A catalytic subunits (PP2Ac) in the leaf responses to conditions that affect tuberization. The responses were monitored by analyzing the expression of the "tuber-specific" genes Patatin and Pin2, which are induced in tubers and leaves during tuber induction. Experiments using PP2A inhibitors, together with PP2Ac expression profiles under conditions that affect tuberization indicate that high sucrose/nitrogen ratio, which promotes tuber formation, increases the transcript levels of Patatin and Pin2, by increasing the activity of PP2As without affecting PP2Ac mRNA or protein levels. Gibberellic acid (GA), a negative regulator of tuberization, down-regulates the transcription of catalytic subunits of PP2As from the subfamily I and decreases their enzyme levels. In addition, GA inhibits the expression of Patatin and Pin2 possibly by a PP2A independent mechanism. PP2Ac down-regulation by GA may inhibit tuberization signaling downstream of the inductive effects of high sucrose/nitrogen ratio. These results are consistent with the hypothesis that PP2As of the subfamily I may positively modulate the signaling pathways that lead to the transcriptional activation of "tuber-specific" genes in leaves, and act as molecular switches regulated by both positive and negative modulators of tuberization. PMID- 20358222 TI - Metabolic and structural rearrangement during dark-induced autophagy in soybean (Glycine max L.) nodules: an electron microscopy and 31P and 13C nuclear magnetic resonance study. AB - The effects of dark-induced stress on the evolution of the soluble metabolites present in senescent soybean (Glycine max L.) nodules were analysed in vitro using (13)C- and (31)P-NMR spectroscopy. Sucrose and trehalose were the predominant soluble storage carbons. During dark-induced stress, a decline in sugars and some key glycolytic metabolites was observed. Whereas 84% of the sucrose disappeared, only one-half of the trehalose was utilised. This decline coincides with the depletion of Gln, Asn, Ala and with an accumulation of ureides, which reflect a huge reduction of the N(2) fixation. Concomitantly, phosphodiesters and compounds like P-choline, a good marker of membrane phospholipids hydrolysis and cell autophagy, accumulated in the nodules. An autophagic process was confirmed by the decrease in cell fatty acid content. In addition, a slight increase in unsaturated fatty acids (oleic and linoleic acids) was observed, probably as a response to peroxidation reactions. Electron microscopy analysis revealed that, despite membranes dismantling, most of the bacteroids seem to be structurally intact. Taken together, our results show that the carbohydrate starvation induced in soybean by dark stress triggers a profound metabolic and structural rearrangement in the infected cells of soybean nodule which is representative of symbiotic cessation. PMID- 20358223 TI - A tomato bZIP transcription factor, SlAREB, is involved in water deficit and salt stress response. AB - Abiotic stresses such as cold, water deficit, and salt stresses severely reduce crop productivity. Tomato (Solanum lycopersicum) is an important economic crop; however, not much is known about its stress responses. To gain insight into stress-responsive gene regulation in tomato plants, we identified transcription factors from a tomato cDNA microarray. An ABA-responsive element binding protein (AREB) was identified and named SlAREB. In tomato protoplasts, SlAREB transiently transactivated luciferase reporter gene expression driven by AtRD29A (responsive to dehydration) and SlLAP (leucine aminopeptidase) promoters with exogenous ABA application, which was suppressed by the kinase inhibitor staurosporine, indicating that an ABA-dependent post-translational modification is required for the transactivation ability of SlAREB protein. Electrophoretic mobility shift assays showed that the recombinant DNA-binding domain of SlAREB protein is able to bind AtRD29A and SlLAP promoter regions. Constitutively expressed SlAREB increased tolerance to water deficit and high salinity stresses in both Arabidopsis and tomato plants, which maintained PSII and membrane integrities as well as water content in plant bodies. Overproduction of SlAREB in Arabidopsis thaliana and tomato plants regulated stress-related genes AtRD29A, AtCOR47, and SlCI7-like dehydrin under ABA and abiotic stress treatments. Taken together, these results show that SlAREB functions to regulate some stress-responsive genes and that its overproduction improves plant tolerance to water deficit and salt stress. PMID- 20358224 TI - Solute permeation across the apoplastic barrier in the perisperm-endosperm envelope in cucumber seeds. AB - An apoplastic barrier consisting of callose and lipid layers in the perisperm endosperm (PE) envelope is known to restrict inward and outward transport of solutes in cucurbit seeds. The present work examines permeability properties of the barrier using cucumber seed as a model system. Osmometrically determined osmotic potential of the apoplastic fluid was used as a basis for osmotic studies aimed at examining solute exclusion from the apoplastic barrier in the PE envelope. The assessment of apoplastic permeability involved measuring the amount of anionic and cationic organic dyes diffused into agarose gel discs through the PE envelope. Ionic/non-ionic solutes including polyethylene glycols having Stokes radii 2,3,5-triphenyltetrazolium chloride (TTC) approximately methyl orange approximately methylene blue > Eosin Y >> Janus green approximately crystal violet approximately Evans Blue. Permeation time(0.5) for DCPIP and TTC was 9.71 and 9.96 h, respectively. Dyes having Stokes radii < 0.5 nm showed significant inward as well as outward diffusion across the PE envelope in contrast to restricted diffusion of dyes having Stokes radii > 0.5 nm. Size exclusion limit for apoplastic barrier in cucumber PE envelope was resolved to be about 0.5 nm by dye permeation and around 0.8 nm by osmotic studies. Dye permeances depended primarily on particle size as described by a quadratic polynomial function rather than on charge or log D. PMID- 20358225 TI - Survival of Schismus arabicus seedlings exposed to desiccation depends on annual periodicity. AB - Schismus arabicus, a desert annual grass, is one of the most common pasture annuals in the deserts of Israel and Asia. S. arabicus exhibits a unique set of adaptations and survival strategies, which enable it to germinate, develop and produce seeds even in years with annual rainfall of less than 100 mm. The current study examined whether an annual rhythm exists in the survival ability of S. arabicus seedlings exposed to desiccation. Our results indicate that survival of S. arabicus seedlings after six different periods of 7 to 42 days of desiccation depended on the month of germination of the caryopses (seeds). Seed germination was 80-100% in all experiments, regardless the month of germination; however, seedlings that germinated in different months varied in their root and shoot elongation rates. None of about 2,500 seedlings that germinated in July (in each of the 4 years) survived the desiccation treatment. The percentages of surviving seedlings in each month of June from 2002 to 2005 were less than 40%. In contrast, over 80% of the seedlings that germinated in each of the months of December and January survived after the desiccation periods of 7-42 days. Seedlings that survived were transferred to 5 L soil pots in which the seedlings developed into mature plants, completed their life cycle and produced seeds that germinated well. The current study demonstrated a novel phenomenon indicating that seedling survival in plants may depend on an annual periodicity according to the date of germination. PMID- 20358226 TI - Overexpression of carbonic anhydrase IX (CAIX) in vulvar cancer is associated with tumor progression and development of locoregional lymph node metastases. AB - Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. The protein is specifically overexpressed in a wide variety of malignant tumors. This study was designed to assess the role of CAIX in primary vulvar cancer. One hundred forty two well-characterized primary vulvar carcinomas were analyzed on a tissue microarray (TMA). Three tissue cores were sampled from each tumor. CAIX expression was determined by immunohistochemistry, using a four-step scoring system. To determine CAIX expression in benign vulvar tissue, we constructed a TMA with 120 samples of normal mucosa and non-neoplastic diseases. CAIX expression was found in 77/135 (57%) of all assessable vulvar cancer specimens and 48 (35.5%) exhibited a moderate or strong expression. CAIX expression in vulvar carcinomas was significantly stronger compared to non-neoplastic vulvar tissue (p < 0.001). High levels of CAIX expression were related to pT stage (p < 0.01), tumor size (p < 0.01), depth of invasion (p < 0.05), as well as inguinal lymph node metastases (p < 0.05). There was also a trend towards shorter recurrence-free patient survival in CAIX-positive compared to CAIX-negative vulvar cancers. CAIX staining results in different tissue cores from the same tumor were homogeneous, raising the possibility of a hypoxia-independent expression. In conclusion, CAIX is overexpressed in the majority of vulvar carcinomas with relationships to advanced tumor stages and development of lymph node metastases. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced vulvar cancer. PMID- 20358227 TI - Response of Pediculus humanus humanus (Pediculidae: Phthiraptera) to water or 70% ethanol immersion and determination of optimal times for measuring toxic effects. AB - Human pediculosis is caused by Pediculus humanus humanus (Linnaeus 1758) and Pediculus humanus capitis (De Geer 1767). We studied the response of body lice to immersion in water and ethanol 70% and determined the optimal times for measuring knockdown and mortality. After immersion in water, all lice remained alive from 5 min to 22 h for both times of exposure. A low proportion of lice were affected after 2 min of immersion in ethanol in the 10-min exposure test, but recovered completely after 5 min. Different proportions of lice were affected between 2 and 7 h after immersion in ethanol, depending on the immersion time. However, a high proportion of lice recovered after 22 h. The results suggest that the optimal times for measuring early knockdown effects of insecticides are the 5-min to 7-h interval for water and 5-min to 1-h interval for ethanol. On the other hand, the best time for measuring mortality is 22 h after immersion. These results should improve the interpretations of the effects of pediculicides in immersion bioassays. PMID- 20358228 TI - Urinary hyaluronidase activity in rats infected with Blastocystis hominis- evidence for invasion? AB - The fact whether Blastocystis hominis can invade has always been in question. Apart from a few sporadic studies such as that done on gnotobiotic guinea pigs which showed surface invasion and mucosal inflammation of the host's intestine caused by B. hominis infection, no real documentation of invasion has been proven. Studies have shown that hyaluronidase is secreted during the penetration into the host's skin and gut by nematode parasites. Hyaluronidase activity in protozoa namely Entamoeba histolytica has also been described previously. This study attempts to determine hyaluronidase in urine samples of B. hominis-infected rats. The presence of hyaluronidase in urine provides an indirect evidence of invasion by B. hominis into colonic epithelium causing the degradation of extracellular matrix proteins namely hyaluronic acid (HA). HA is depolymerized by hyaluronidase which may be used by organisms to invade one another. In this study, the levels of urinary hyaluronidase of Sprague-Dawley rats infected with B. hominis were monitored for 30 days. Hyaluronidase levels in the infected rats were significantly higher on days 28 and 30 compared to the day before inoculation (P < 0.01 and P < 0.05, respectively). During this stage, parasitic burden in infected stools was also at a high level. Proinflammatory cytokines, interleukin-6 and interleukin-8, were also significantly higher (P < 0.05) in the serum of infected rats. The study demonstrates that since no other pathogen was present and that amoeboid forms of the parasites have been shown to exist previously, the elevated levels of hyaluronidase in this preliminary finding suggests that the organism is capable of having invasion or penetration activity in the hosts' intestine. PMID- 20358229 TI - Screening of antileishmanial activity from marine sponge extracts collected off the Tunisian coast. AB - The present study reports on the in vitro antileishmanial activity of two Ircinidae (Dictyoceratida, Demospongiae, Porifera) Ircinia spinosula and Sarcotragus sp. Sampled from the east coast of Tunisia. The ethyl acetate, dichloromethane, and aqueous extracts were tested against Leishmania major promastigotes. The anti-proliferative activity was checked using different extracts concentration during 72 h. We found that the IC50 (sub-inhibitory concentration) values ranged from 1.39 to 264.67 mug/ml. The most active extract was that from sarcotragus sp dichloromethane extract. Microscopic observations showed that the extracts promoted cellular alterations and induce enlargement of the nucleus and modification of the parasite shape. These promising results in relation with in vitro antileishmanial activity open the way for complementary investigation in order to purify and identify active molecules. PMID- 20358230 TI - Disorders of sex development and Diamond-Blackfan anemia: is there an association? AB - Diamond-Blackfan anemia (DBA) is a rare disorder characterized by congenital pure red cell aplasia. Mutations in ribosomal protein S19 (RPS19) have been identified in 25% of DBA patients. More recently, mutations in other ribosomal protein genes, namely RPS7, RPS15, RPS24, RPS17, RPS27A, RPL35a, RPL36, RPL11, and RPL5, have also been found in patients with DBA. Approximately 30-40% of affected patients have various associated physical anomalies, mostly craniofacial and at the extremities, but also cardiac or urogenital malformations. Anomalies of the urogenital tract in DBA patients comprise changes in the kidney (dysplasia, agenesis, duplication, horseshoe kidney) and genitalia (hypospadias). To date, disorders of sex development (DSD) have only been described once in association with DBA. We report here four DBA patients who exhibited DSD. PMID- 20358231 TI - ANCA-associated vasculitides-lessons from the adult literature. AB - Anti-neutrophil cytoplasmic antigen antibody (ANCA)-associated disease is a rare manifestation of primary systemic vasculitis in paediatric patients but one that carries significant morbidity, potential long-term disability and early mortality. It therefore requires a high index of suspicion, targeted investigation, prompt treatment and long-term follow-up with specialist input at every stage. The well-recognised diversity and overlap in clinical, laboratory and histopathological features of the ANCA-associated systemic vasculitides continue to hamper accurate diagnosis, confounding epidemiological data and necessitating a blanket approach to treatment, which is largely extrapolated from studies in adult patients and carries significant side-effects. Herein we summarise current knowledge of the epidemiology, pathogenesis, principal manifestations, investigation and evidence-based management, extrapolated from adult studies, of these disorders. We also discuss recent efforts towards classification of the childhood vasculitides that emphasise the value of histological diagnosis. Progress in our understanding of the pathophysiology underlying ANCA-associated disease should lead to targeted, safer and more effective therapies for these conditions. Nonetheless, many questions remain outstanding, and academic paediatricians face real challenges in identifying and collating the few cases they encounter into study cohorts. Meeting this challenge will require international collaboration, not only among paediatricians but also with the specialists taking over care of these patients as they reach adulthood. PMID- 20358232 TI - The influence of climate on durum wheat quality in Tuscany, Central Italy. AB - Climate and meteorological conditions greatly affect agricultural activities, modifying plant responses and determining the quantity and the quality of production. In this respect, the aim of this research was to analyze the quality of winter durum wheat (Triticum turgidum L. var. durum), in terms of protein content through the use of meteorological information. Meteorological conditions were described utilizing both local weather station data (air temperature, cumulated precipitation) and large-scale information available freely on the internet, such as geopotential height (GPH), sea surface temperature (SST), and the North Atlantic Oscillation (NAO) index. The analysis was carried out for the period 1997-2009 in the Tuscany region, Central Italy. Grain protein was positively correlated with air temperature during the February to June period, and negatively with cumulative precipitation during the entire period from November to June. Protein content was also negatively correlated with 500 hPa GPH over Gibraltar and North-Western Africa during the March to June period and with the SST of the Atlantic Ocean south-west of the Canary Islands during the January to June period. Finally, with regard to the NAO, winter durum wheat quality was positively correlated with the specific index for several months, in particular during the winter period. These results demonstrate that precipitation and air temperature over the production area represent two crucial variables driving the vegeto-productive responses of winter durum wheat. On the other hand, the use of large-scale meteorological information showed great potential from the perspective of a local quality forecast system setup. PMID- 20358233 TI - [Alkylphosphocholines inhibit lens epithelial cell proliferation and attachment]. AB - BACKGROUND: Posterior capsule opacification (PCO) is one of the major concerns in modern cataract surgery. Ten years after successful surgery, Nd:YAG capsulotomy is required in up to 42% of patients with an acrylic sharp-edged intraocular lens (IOL). Some accommodative and multifocal IOLs display even higher capsulotomy rates. Pharmacologic prophylaxis with alkylphosphocholines (APCs) could be a novel option in PCO prevention. METHODS: The human lens epithelial cell line HLE B3 served as an in-vitro model. After incubation with APCs in different concentrations (0.01, 0.1, and 1 mM), the trypan blue exclusion assay and the live/dead test were performed at serum concentrations of only 5%. Cell proliferation was assessed with the MTT test. Evaluation of cell attachment was done with fibronectin- and laminin-coated wells. RESULTS: APCs can inhibit the proliferation of human lens epithelial cells in the presence of only 5% serum in a dose-dependent manner. Proliferation inhibition of 60% and attachment inhibition of about 50% were reached at concentrations of 0.1 uM. CONCLUSION: APCs inhibit proliferation and attachment of human lens epithelial cells in nontoxic concentrations in vitro. The substance can be applied topically, and an intraoperative application for pharmacologic PCO prophylaxis is feasible. PMID- 20358234 TI - The effect of dopamine on pain-related neurons in the parafascicular nucleus of rats. AB - Dopamine (DA) regulates pain perception in the central nervous system (CNS). However, the mechanism of the action of DA in pain-related neurons of the parafascicular nucleus (Pf) is not clear. The present study aimed to determine the effect of DA and its receptor antagonist, droperidol on the pain-evoked responses of the pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the Pf of rats and to analyze the mechanisms underlying this effect. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN and PIN in the Pf were recorded by using a glass microelectrode. The results showed that, in the Pf, intra-Pf microinjection of DA (5 microg/0.5 microl) increased the frequency of noxious stimulation induced discharges of the PEN and decreased the frequency of those of the PIN, while the intra-Pf administration of droperidol (0.15 microg/0.5 microl) produced an opposite effect. On the basis of the above-mentioned findings, we could conclude that DA and its receptors in the Pf are involved in the modulation of the nociceptive response by regulating the discharges of PEN and PIN. PMID- 20358235 TI - Atopic conditions and mental health problems: a 3-year follow-up study. AB - The aim of this study was to test the hypothesis that atopic conditions at 15/16 years of age affect both internalized and externalized mental health problems 3 years later. Combined school and postal survey was conducted in urban and rural settings. A total of 3,674 adolescents (70.1% response rate) were followed at two time points and interviewed with similar questionnaires at baseline and follow up. Hopkins Symptoms Checklist (HSCL-10) was used to assess internalized problems, and two subscales (conduct problems and hyperactivity) from the Strength and Difficulties Questionnaire to measure externalized mental health problems. The atopic conditions investigated were asthma, hay fever and eczema by asking the adolescents whether these conditions were present or not. There was an increase in the prevalence of internalized mental health problems from about 17 25% and a decrease in externalized mental health problems and number of atopic conditions in the follow-up period. Of the atopic conditions, hay fever was most prevalent with about 34% at 15 years of age and 20% at 18. The asthma prevalence was at 10 and 5% and eczema at 25 and 10%, respectively. Internalized mental health problems among girls were significantly associated with atopic conditions 3 years earlier, also after controlling for confounding variables. To live with atopic conditions seem to affect the mood and level of anxiety among adolescent girls. This should be kept in mind by health professionals treating young girls with atopic conditions. PMID- 20358236 TI - Desulfosporosinus acidiphilus sp. nov.: a moderately acidophilic sulfate-reducing bacterium isolated from acid mining drainage sediments : New taxa: Firmicutes (Class Clostridia, Order Clostridiales, Family Peptococcaceae). AB - An obligately anaerobic, spore-forming, acidophilic sulfate-reducing bacterium, strain SJ4(T), was isolated from an acid mining effluent decantation pond sediment sample (pH around 3.0). Cells were Gram negative, non-motile, curved rods occurring singly. Strain SJ4(T) grew at pH 3.6-5.5 with an optimum at pH 5.2. Strain SJ4(T) utilized H(2), lactate, pyruvate, glycerol, glucose, and fructose as electron donors. Lactate and glucose were weakly used. Sulfate was used as electron acceptors, but not sulfite, elemental sulfur, arsenate (V), and fumarate. The G + C content of genomic DNA was 42.3 mol% (HPLC). 16S rRNA gene sequence analysis indicated that strain SJ4(T) belonged to the genus Desulfosporosinus within the family Peptococcaceae in the phylum Firmicutes. The level of 16S rRNA gene sequence similarity with other Desulfosporosinus species was 94.7-96.2%, D. orientis DSM 765(T) (similarity of 96.2%) and D. auripigmenti DSM 13351(T) (similarity of 95%) being its closest relatives. DNA-DNA relatedness values with D. orientis and D. auripigmenti were 16.5 and 31.8%, respectively. On the basis of phenotypic, phylogenetic, and genetic characteristics, strain SJ4(T) represents a novel species within the genus Desulfosporosinus, for which the name Desulfosporosinus acidiphilus sp. nov. is proposed. The type strain is SJ4(T) (=DSM 22704(T) = JCM 16185(T)). PMID- 20358237 TI - Characterization of Microaerobacter geothermalis gen. nov., sp. nov., a novel microaerophilic, nitrate- and nitrite-reducing thermophilic bacterium isolated from a terrestrial hot spring in Tunisia. AB - A novel thermophilic anaerobic and microaerophilic bacterium (optimal growth in the presence of 5-10% O(2)), strain Nad S1(T) was isolated from the terrestrial hot spring of Hammam Sidi Jdidi, Nabeul, Tunisia. Cells were motile rods having a Gram-positive cell wall structure. Strain Nad S1(T) grew optimally at 55 degrees C (range 37-70 degrees C). Optimum pH for growth was 6.5-7.0. It was halotolerant growing with NaCl up to 7% (optimum concentration 1.5-3.0%). It grew chemoorganotrophically on various carbohydrates, organic-acids and amino-acids as energy sources, or chemolithotrophically on H(2) using nitrate, as terminal electron acceptor. Beside oxygen (under microaerobic conditions) and nitrate, nitrite was also used. Nitrate was completely reduced to N(2). No fermentation occurred. The genomic DNA G + C content was 41.8 mol%. Based on 16S rRNA gene sequence analysis, strain Nad S1(T) belongs to the Bacillaceae family within the class 'Bacilli'. Because of its phylogenetic and phenotypic characteristics, we propose this isolate to be assigned as a novel genus and a novel species within the domain Bacteria, Microaerobacter geothermalis gen. nov., sp. nov. The type strain is Nad S1(T) (=DSM 22679(T) =JCM 16213(T)). PMID- 20358238 TI - Limited mouth opening after primary therapy of head and neck cancer. AB - OBJECTIVES: Patients after surgery and radiation/chemoradiation for treatment of head and neck cancer often suffer from oral complications. These problems may be caused by surgery and radiation. Patients complain, for example, of swallowing problems and limited mouth opening (trismus). METHODS: The maximal interincisal mouth opening (MIO) was measured in patients treated with surgery and radiation/chemoradiation for head and neck cancer at the Department of Otorhinolaryngology at the University of Rostock. These patients also completed a 20-item questionnaire concerning nutritional, sensual, and speech disorders and pain. RESULTS: One hundred one patients (16 female and 85 male) returned the questionnaire and were included in the study. About 50% of the patients had a limited mouth opening (<36 mm); patients with oropharyngeal cancer had a significant higher risk for trismus (p = .024) than patients with other head and neck cancers, especially compared to patients with laryngeal cancer (p = .013). The questionnaire showed that especially patients with oral cancer report about problems with opening the mouth (73%), eating (65%), drinking (73%), xerostomia (92%), speech disorders (68%), and voice (62%). Patients with laryngeal cancer only reported about problems with xerostomia (62%), speech (83%), and voice (90%), similar to patients with pharyngeal cancer. CONCLUSIONS: About half of the patients who underwent primary treatment for oral and oropharyngeal cancer developed trismus and reported about problems with opening the mouth, eating, drinking, dry mouth, voice, and speech. Trismus has a negative impact on quality of life and should be a focus in the postoperative management of patients with oral and oropharyngeal cancer, and, if diagnosed, special treatment should be initialized. PMID- 20358239 TI - Incidence of contralateral occult inguinal hernia found at the time of laparoscopic trans-abdominal pre-peritoneal (TAPP) repair. AB - BACKGROUND: Trans-abdominal laparoscopic inguinal hernia repair allows rapid assessment and exploration of the contralateral groin and repair of an occult hernia. Although previous studies have shown that the totally extra-peritoneal (TEP) hernia repair can be used to assess the contralateral groin, there is little data pertaining to the trans-abdominal pre-peritoneal (TAPP) approach. The aim of this study was to document the incidence of occult contralateral hernia at the time of TAPP hernia repair. METHODS: Data were collected prospectively from all patients undergoing laparoscopic TAPP hernia repair in a District General Hospital over a three-year period. Two specialist laparoscopic/upper gastrointestinal surgeons undertook all of the operations and telephone follow-up was carried out by a dedicated laparoscopic specialist nurse. RESULTS: A total of 310 patients underwent hernia surgery. Four cases were excluded, leaving 306 patients in the study. The male:female ratio was 10.5:1, with a median age of 59 years. Two hundred and six (67%) patients were booked for a unilateral hernia repair; of these, a contralateral hernia was found and repaired in 45 (22%). In 76 cases where a bilateral repair was planned, 61 (80%) went on to have both groin defects repaired. In the remaining 20%, the clinical suspicion of bilateral hernia was revised at the time of surgery to unilateral only. Twenty (7%) patients were booked to undergo a unilateral repair with the possibility of a contralateral hernia--in this group, the suspected contralateral defect was confirmed in 6 (30%) cases. Four (1%) cases were booked as femoral repairs, one of which was found to be an inguinal hernia. The clinical diagnostic accuracy was 78%. CONCLUSION: Accurate incidence figures of an occult contralateral inguinal hernia will enhance the pre-operative information given to patients and may impact on resource allocation and planning theatre logistics. Finding and repairing an occult contralateral hernia at the time of TAPP has the distinct advantage that it saves the patient from further symptoms and from another operation with its associated potential morbidity. PMID- 20358240 TI - Cloning and functional identification of delta5 fatty acid desaturase gene and its 5'-upstream region from marine fungus Thraustochytrium sp. FJN-10. AB - A gene encoding delta5 fatty acid desaturase (fad5) was cloned from marine fungus Thraustochytrium sp. FJN-10, a species capable of producing docosahexaenoic acid. The open reading frame of fad5 was 1,320 bp and encoded a protein comprising 439 amino acids. Expression of the fad5 in Saccharomyces cerevisiae INVSC1 revealed that FAD5 is able to introduce a double bond at position 5 of the dihomo-gamma linolenic acid (20:3 Delta(8,11,14)), resulting in arachidonic acid (20:4 Delta(5,8,11,14)) with a conversion rate of 56.40% which is the highest among engineering yeasts reported so far. The 5'-upstream region of fad5 was cloned by LA-PCR and analyzed. Phylogenetic analysis of this sequence with the 5'-upstream region of other delta5 desaturases showed that the 5'-upstream region of fad5 from Thraustochytrium share the smallest evolution distance with human and rhesus. Computational analysis of the nucleotide sequence of the 5'-upstream region of fad5 has revealed several basic transcriptional elements including five TATA boxes, three CCAAT boxes, 12 GC boxes, and several putative target-binding sites for transcription factors such as HSF, CAP, and ADR1. Preliminary functional analysis of this promoter in S. cerevisiae shows that the 5'-upstream region of fad5 could drive the expression of green fluorescent protein. PMID- 20358241 TI - Surgical management of brainstem cavernomas: selection of approaches and microsurgical techniques. AB - This study reviewed surgical experience with brainstem cavernomas in an attempt to define optimal surgical approaches and risks associated with surgical management. Clinical courses were retrospectively reviewed for 36 consecutive patients (12 men, 24 women; mean age, 42 years) who underwent microsurgical resection of brainstem cavernomas between 1996 and 2006. Medical records, surgical records, and neuroimaging examinations were evaluated. All 36 patients presented with > or =1 hemorrhage from the cavernomas and preoperatively displayed some neurological symptoms. Surgical approach was midline suboccipital for 16 pontine and/or medullary cavernomas under the floor of the fourth ventricle, retrosigmoid for 10 lateral mesencephalic, pontine, and/or medullary cavernomas, occipital transtentorial for 2 thalamomesencephalic and 3 mesencephalic cavernomas, combined petrosal for 2 pontine cavernomas, and other for 3 cavernomas. Complete resection according to postoperative magnetic resonance imaging was achieved in 33 of 36 patients. No mortality was encountered in this study. New neurological deficit occurred in the early postoperative period for 18 patients, but was transient in 15 of these. Neurological state as of final follow-up was improved in 16 patients (44%), unchanged in 17 (47%), and worsened in 3 (8%) compared with preoperatively. In conclusion, symptomatic brainstem cavernomas should be considered for surgical treatment. Careful selection of the optimal operative approach and a meticulous microsurgical technique are mandatory. PMID- 20358242 TI - Physiological and psychophysical modeling of the precedence effect. AB - Many past studies of sound localization explored the precedence effect (PE), in which a pair of brief, temporally close sounds from different directions is perceived as coming from a location near that of the first-arriving sound. Here, a computational model of low-frequency inferior colliculus (IC) neurons accounts for both physiological and psychophysical responses to PE click stimuli. In the model, IC neurons have physiologically plausible inputs, receiving excitation from the ipsilateral medial superior olive (MSO) and long-lasting inhibition from both ipsilateral and contralateral MSOs, relayed through the dorsal nucleus of the lateral lemniscus. In this model, physiological suppression of the lagging response depends on the inter-stimulus delay (ISD) between the lead and lag as well as their relative locations. Psychophysical predictions are generated from a population of model neurons. At all ISDs, predicted lead localization is good. At short ISDs, the estimated location of the lag is near that of the lead, consistent with subjects perceiving both lead and lag from the lead location. As ISD increases, the estimated lag location moves closer to the true lag location, consistent with listeners' perception of two sounds from separate locations. Together, these simulations suggest that location-dependent suppression in IC neurons can explain the behavioral phenomenon known as the precedence effect. PMID- 20358243 TI - Visualization of through-plane blood flow measurements obtained from phase contrast MRI. AB - The purpose of this work was to develop a visualization method for concurrent observation of both velocity and magnitude data obtained from through-plane velocity measurements using phase-contrast magnetic resonance imaging. Magnitude and velocity images were combined using an opacity transfer function (OTF) where the opacity was a function of a velocity range defined by the velocity encoding (v (enc)) parameter. Measured velocities were color-coded according to a predefined color scale and then combined into one image with the gray-scale magnitude image according to the OTF. In the combined images, simultaneous information of velocity and anatomy was presented. The proposed visualization method facilitated the understanding of how the measured blood flow was related to the underlying anatomy. Results are shown where the method is used to visualize blood flow measurements in the ascending aorta and the aortic valve. Adjustments of the OTF render possible identification of the peak velocities and their localization. Forward and backward blood flow is easily shown when applying appropriate OTF and color-coding. An advantage when using the proposed method is the ability of developing standardized protocol settings since the velocity information is quantitative and not relative as is the case for data obtained from the magnitude images. The intended application of the visualization method is the analysis of common flow studies used in the diagnosis of different cardiovascular diseases. PMID- 20358244 TI - Successful treatment of three children with post-neurosurgical multidrug resistant Acinetobacter baumannii meningitis. PMID- 20358245 TI - An outbreak of Burkholderia cenocepacia bacteremia in immunocompromised oncology patients. AB - BACKGROUND: Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. METHODS: A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). RESULTS: Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. CONCLUSIONS: B. cenocepacia is an emerging nosocomial pathogen among oncology patients. PMID- 20358246 TI - Lethal influenza B myocarditis in a child and review of the literature for pediatric age groups. AB - CASE PRESENTATION: We report on the case of a 5 year-old girl who developed fulminant myocarditis due to acute infection with influenza virus type B. Cardiac arrest occurred suddenly, resuscitation efforts were not successful, and the patient died of congestive heart failure 24 h after admission to the hospital. DIAGNOSIS: Lymphocytic infiltration of cardiac tissues and virologic studies confirmed the suspected diagnosis of acute viral myocarditis. CONCLUSION: In conclusion, influenza virus type B is one of the infective agents that can cause rapid and fatal myocarditis in previously healthy children. Early cardiac support may be the only option to prevent fatal outcome. PMID- 20358247 TI - Rothia aeria acute bronchitis: the first reported case. PMID- 20358248 TI - Pancytopenia in a patient with Lyme disease. PMID- 20358249 TI - Expression of defensins in non-infected araneomorph spiders. AB - Defensins are a major family of antimicrobial peptides found throughout the phylogenetic tree. From the spider species: Cupiennius salei, Phoneutria reidyi, Polybetes pythagoricus, Tegenaria atrica, and Meta menardi, defensins belonging to the 'ancestral' class of invertebrate defensins were cloned and sequenced. The deduced amino acid sequences contain the characteristic six cysteines of this class of defensins and reveal precursors of 60 or 61 amino acid residues. The mature peptides consist of 37 amino acid residues, showing up to 70% identities with tick and scorpion defensins. In C. salei, defensin mRNA was found to be constitutively expressed in hemocytes, ovaries, subesophageal nerve mass, hepatopancreas, and muscle tissue. This is the first report presenting and comparing antimicrobial peptides belonging to the family of defensins from spiders. PMID- 20358250 TI - Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A. AB - Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. PMID- 20358251 TI - Endocytosis of hepatitis C virus non-enveloped capsid-like particles induces MAPK ERK1/2 signaling events. AB - Although HCV is an enveloped virus, naked nucleocapsids have been reported in the serum of infected patients. The HCV core particle serves as a protective capsid shell for the viral genome and recombinant in vitro assembled HCV core particles induce strong specific immunity. We investigated the post-binding mechanism of recombinant core particle uptake and its intracellular fate. In hepatic cells, these particles are internalized, most likely in a clathrin-dependent pathway, reaching early to late endosomes and finally lysosomes. The endocytic acidic milieu is implicated in trafficking process. Using specific phosphoantibodies, signaling pathway inhibitors and chemical agents, ERK(1/2) was found to be activated in a sustained way after endocytosis, followed by downstream immediate early genes (c-fos and egr-1) modulation. We propose that the intriguing properties of cellular internalization of HCV non-enveloped particles can induce specific ERK(1/2)-MAPKs events that could be important in HCV life cycle and pathogenesis of HCV infection. PMID- 20358255 TI - Ecological links between water storage behaviors and Aedes aegypti production: implications for dengue vector control in variable climates. AB - Understanding linkages between household behavior and Aedes aegypti (L.) larval ecology is essential for community-based dengue mitigation. Here we associate water storage behaviors with the rate of A. aegypti pupal production in three dengue-endemic Colombian cities with different mean temperatures. Qualitative, semi-structured interviews and pupal counts were conducted over a 7-15-day period in 235 households containing a water storage vessel infested with larvae. Emptying vessels more often than every 7 days strongly reduced pupal production in all three cities. Emptying every 7-15 days reduced production by a similar magnitude as emptying <7 days in Armenia (21.9 degrees C), has a threefold smaller reduction as compared to <7 days in Bucaramanga (23.9 degrees C), and did not reduce production in Barranquilla (29.0 degrees C). Lidding vessels reduced mosquito production and was most feasible in Barranquilla because of container structure. Vessel emptying strongly correlated with usage in Barranquilla, where many households stored water in case of interruptions in piped service rather than for regular use. In the cooler cities, >90% of households regularly used stored water for washing clothes, generating a weaker correlation between emptying and usage. Emptying was less frequent in the households surveyed in the dry season in all three cities. These results show that A. aegypti production and human behaviors are coupled in a temperature-dependent manner. In addition to biological effects on aquatic stages, climate change may impact A. aegypti production through human behavioral adaptations. Vector control programs should account for geographic variation in temperature and water usage behaviors in designing targeted interventions. PMID- 20358252 TI - Retroviral reverse transcriptases. AB - Reverse transcription is a critical step in the life cycle of all retroviruses and related retrotransposons. This complex process is performed exclusively by the retroviral reverse transcriptase (RT) enzyme that converts the viral single stranded RNA into integration-competent double-stranded DNA. Although all RTs have similar catalytic activities, they significantly differ in several aspects of their catalytic properties, their structures and subunit composition. The RT of human immunodeficiency virus type-1 (HIV-1), the virus causing acquired immunodeficiency syndrome (AIDS), is a prime target for the development of antiretroviral drug therapy of HIV-1/AIDS carriers. Therefore, despite the fundamental contributions of other RTs to the understanding of RTs and retrovirology, most recent RT studies are related to HIV-1 RT. In this review we summarize the basic properties of different RTs. These include, among other topics, their structures, enzymatic activities, interactions with both viral and host proteins, RT inhibition and resistance to antiretroviral drugs. PMID- 20358256 TI - Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness. AB - AIM: We conducted this phase II study in an effort to evaluate the efficacy and safety of a gemcitabine single chemotherapy as a second-line treatment for biliary tract cancer (BTC) patients who evidenced disease progression after the administration of 5-fluorouracil (5-FU)-based palliative chemotherapy. PATIENTS AND METHOD: Patients treated previously with 5-FU-based palliative treatment as a BTC were enrolled in this study. Treatment consisted of gemcitabine at a dosage of 1,250 mg/m(2) administered intravenously over a 30-minute period on days 1 and 8 of each 21-day cycle until progression. RESULTS: Between Feb. 2006 and July 2009, a total of 32 patients were assigned to treatment groups. 16 patients (50%) had cancers of intra-hepatic cholangiocarcinoma, 12 patients (37.5%) had gall bladder cancer, and 4 patients (12.5%) had extra-hepatic cholangiocarcinoma. In the 29 patients whose tumor responses were evaluated, two achieved a partial response, with an overall response rate of 6.9% (95% confidence interval [CI]: 0.0-16.7%). Six patients (20.7%) evidenced stable disease and 21 patients (72.4%) evidenced progression during the course of treatment. The median follow-up duration was 23.2 months (range: 3.0-53.1 months). The median time to progression (TTP) was 1.6 months (95% CI: 1.3-1.9 months), and the median overall survival (OS) time was 4.1 months (95% CI: 2.7-5.5 months). Poor performance status (ECOG 2) in patients was predictive of shorter TTP. Lower albumin levels (<3.5 g/dL) in patients were predictive of shorter TTP and OS. CONCLUSIONS: Despite first salvage chemotherapy in the phase II study for patients with 5-FU refractory BTC, the results in terms of RR, TTP, and OS were lower than expected. However, selected patients with good performance status and sufficient albumin levels may have derived some survival benefits from salvage chemotherapy. PMID- 20358257 TI - Trachoma control in two Central Australian Aboriginal communities: a case study. AB - This prospective case study assessed the additional impact of environmental changes (E) within the SAFE strategy in controlling trachoma in two Aboriginal communities (populations 315 and 385) in Central Australia. Baseline levels for trachoma, facial cleanliness, and nasal discharge were measured in children <15 years old. Health and facial cleanliness promotion were initiated in each community and housing and environmental improvements were made in one community. Azithromycin was distributed to all members of each community (coverage 55-73%). Assessments of trachoma and facial cleanliness were made at 3, 6, and 12 months post-intervention. Baseline trachoma rates were similar for the two communities (48 and 50%). Rates were significantly lower at 3, 6, and 12 months compared to baseline, but there was no significant difference between the two communities. The A/F components of the SAFE strategy significantly reduced the prevalence of trachoma; however, while the E intervention did not bring any apparent benefits, several factors might have masked them. PMID- 20358253 TI - Protein folding and aggregation in bacteria. AB - Proteins might experience many conformational changes and interactions during their lifetimes, from their synthesis at ribosomes to their controlled degradation. Because, in most cases, only folded proteins are functional, protein folding in bacteria is tightly controlled genetically, transcriptionally, and at the protein sequence level. In addition, important cellular machinery assists the folding of polypeptides to avoid misfolding and ensure the attainment of functional structures. When these redundant protective strategies are overcome, misfolded polypeptides are recruited into insoluble inclusion bodies. The protein embedded in these intracellular deposits might display different conformations including functional and beta-sheet-rich structures. The latter assemblies are similar to the amyloid fibrils characteristic of several human neurodegenerative diseases. Interestingly, bacteria exploit the same structural principles for functional properties such as adhesion or cytotoxicity. Overall, this review illustrates how prokaryotic organisms might provide the bedrock on which to understand the complexity of protein folding and aggregation in the cell. PMID- 20358258 TI - QM/MM based 3D QSAR models for potent B-Raf inhibitors. AB - Three dimensional (3D) quantitative structure-activity relationship studies of 37 B-Raf inhibitors, pyrazole-based derivatives, were performed. Based on the co crystallized compound (PDB ID: 3D4Q), several alignment methods were utilized to derive reliable comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. Receptor-guided alignment with quantum mechanics/molecular mechanics (QM/MM) minimization led to the best CoMFA model (q (2) = 0.624, r (2) = 0.959). With the same alignment, a statistically reliable CoMSIA model with steric, H-bond acceptor, and hydrophobic fields was also derived (q (2) = 0.590, r (2) = 0.922). Both models were validated with an external test set, which gave satisfactory predictive r (2) values of 0.926 and 0.878, respectively. Contour maps from CoMFA and CoMSIA models revealed important structural features responsible for increasing biological activity within the active site and explained the correlation between biological activity and receptor-ligand interactions. New fragments were identified as building blocks which can replace R1-3 groups through combinatorial screening methods. By combining these fragments a compound with a high bioactivity level prediction was found. These results can offer useful information for the design of new B-Raf inhibitors. PMID- 20358259 TI - Prediction of SAMPL2 aqueous solvation free energies and tautomeric ratios using the SM8, SM8AD, and SMD solvation models. AB - We applied the solvation models SM8, SM8AD, and SMD in combination with the Minnesota M06-2X density functional to predict vacuum-water transfer free energies (Task 1) and tautomeric ratios in aqueous solution (Task 2) for the SAMPL2 test set. The bulk-electrostatic contribution to the free energy of solvation is treated as follows: SM8 employs the generalized Born model with the Coulomb field approximation, SM8AD employs the generalized Born approximation with asymmetric descreening, and SMD solves the nonhomogeneous Poisson equation. The non-bulk-electrostatic contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell is treated as a sum of terms that are products of geometry-dependent atomic surface tensions and solvent-accessible surface areas of the individual atoms of the solute. On average, three models tested in the present work perform similarly. In particular, we achieved mean unsigned errors of 1.3 (SM8), 2.0 (SM8AD), and 2.6 kcal/mol (SMD) for the aqueous free energies of 30 out of 31 compounds with known reference data involved in Task 1 and mean unsigned errors of 2.7 (SM8), 1.8 (SM8AD), and 2.4 kcal/mol (SMD) in the free energy differences (tautomeric ratios) for 21 tautomeric pairs in aqueous solution involved in Task 2. PMID- 20358260 TI - Evaluation of the value of rapid D-dimer test in conjunction with cardiac troponin I test for early risk stratification of myocardial infarction. AB - We sought to determine the diagnostic value of a D-dimer test for myocardial infarction (MI). The prospective cohort study was carried in the ED of a university hospital. All included patients were tested for D-dimer and cardiac troponin I (cTnI) on ED admission and additional cTnI 6 h later. AMI was retrospectively confirmed by employing the ESC-ACC-AHA-WHF 2007 universal definition. The discriminative value of D-dimer test was assessed by ROC curve analysis. Multivariate analysis was used to identify independent risk factors associated with D-dimer elevation other than MI. A total of 178 patients were included in this study. Median D-dimer levels were significantly higher in MI patients. A D-dimer value greater than 200 ng/ml was significantly associated with MI. When used alone, the test has a high sensitivity of 91.8% but a low specificity of 23.9%. Combined use of cTnI and D-dimer tests raised the sensitivity to 98.4% and helped early triage a subgroup of low risk patients. However, the test had the downside of 58% false positives. High false positives could be partly explained by the high prevalence of underlying hypercoagulable comorbidities. Diabetes mellitus with chronic renal insufficiency was identified as the strongest risk factor associated with D-dimer elevation in patients without MI. D-dimer test alone has a low diagnostic value for MI. Co-existing hypercoagulable conditions may confound the results. Combining cTnI and D-dimer tests enables early identification a low risk group of patients for MI at the cost of high false positives. PMID- 20358261 TI - The putative Arabidopsis zinc transporter ZTP29 is involved in the response to salt stress. AB - Salt stress leads to a stress response, called the unfolded protein response (UPR), in the endoplasmic reticulum (ER). UPR is also induced in a wide range of organisms by zinc deficiency. However, it is not clear whether regulation of zinc levels is involved in the initiation of the UPR in plant response to salt stress. In this study, a putative zinc transporter, ZTP29, was identified in Arabidopsis thaliana. ZTP29 localizes to the ER membrane and is expressed primarily in hypocotyl and cotyledon tissues, but its expression can be induced in root tissue by salt stress. T-DNA insertion into the ZTP29 gene led to NaCl hypersensitivity in seed germination and seedling growth, leaf etiolation, and widening of cells in the root elongation zone. In addition, in ztp29 mutant plants, salt stress induced upregulation of the UPR pathway genes BiP2 and bZIP60 was inhibited. Furthermore, under conditions of salt stress, upregulation of BiP2 and bZIP60 was inhibited by treatment with high concentrations of zinc in both control and ztp29 plants. However, zinc chelation restored salt stress-induced BiP2 and bZIP60 upregulation in ztp29 mutant plants. These experimental results suggest that ZTP29 is involved in the response to salt stress, perhaps through regulation of zinc levels required to induce the UPR pathway. PMID- 20358262 TI - Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies. AB - In pharmaco-epidemiology, the use of drugs is the determinant of interest when studying exposure-outcome associations. The increased availability of computerized information about drug use on an individual basis has greatly facilitated analyses of drug effects on a population-based scale. It seems likely that many negative findings in the early days of pharmaco-epidemiology can be explained by non-differential misclassification because of too simple (yes/no) exposure measures. In this paper, the authors discuss the importance of an adequate definition of drug exposure in pharmaco-epidemiological research and how this time-varying determinant can be analyzed in cohort studies. To reduce the risk of non-differential misclassification, a precise definition of exposure is mandatory and it is important to distinguish the complete follow-up period of a population into mutually exclusive episodes of non-use, past use and current use for each individual. By analyzing exposure to drugs as a time-dependent variable in a Cox regression model, cohort studies with complete coverage of all filled prescriptions can provide us with valid and precise risk estimates of drug outcome associations. However, such estimates may be biased in the presence of time-dependent confounders which are themselves affected by prior exposure. PMID- 20358263 TI - Multivariate data analysis of factors affecting the in vitro dissolution rate and the apparent solubility for a model basic drug substance in aqueous media. AB - PURPOSE: To evaluate the usefulness of a miniaturized rotating disk equipment for the determination of factors influencing the in vitro dissolution rate, G, of a model basic drug substance (terfenadine) in different aqueous media, using experimental design and multivariate data analysis. The apparent solubility, S, was included in the chemometric study. METHODS: The dissolution rate was determined with a miniaturized rotating disk apparatus and the solubility by shake-flask methodology. Media were based on acetate, phosphate or maleate buffers-the latter used in fasted state simulated intestinal fluid (FaSSIF-V2). The chemometric analyses included fractional factorial design, principal component analysis (PCA) and orthogonal partial least squares (OPLS). Quantifications were made with a RP-HPLC-DAD system. RESULTS: The most influential factor for both G and S of terfenadine in the different media was pH. Apart from the ionic strength and sodium chloride concentration in the acetate medium, the effects of the other variables were insignificant, implying no wetting effect of the surfactants. CONCLUSIONS: The miniaturized rotating disk equipment was suitable to use, in conjunction with the chemometric analyses, in the evaluation of the factors affecting the in vitro dissolution rate. The apparent solubility was found to be influenced by the same factors as G. PMID- 20358264 TI - The lysosomal trafficking regulator interacting protein-5 localizes mainly in epithelial cells. AB - Endocytosis, subsequent protein sorting into multivesicular bodies (MVBs), and eventual degradation in lysosomes compose an important mechanism for controlling protein expression on the plasma membrane. The lysosomal trafficking regulator interacting protein-5 (LIP5) is part of the complex protein machinery involved in MVB biosynthesis. LIP5 interacts with other players of the ESCRT machinery as well as with two known cargo proteins, AQP2 and EGFR, whose degradation is affected upon reduction of LIP5 expression. To investigate the expression and localization pattern of LIP5, we studied LIP5 protein expression in a mouse tissue panel and subjected various rodent and human tissues to immunohistochemistry. Immunoblotting revealed that, except for jejunum, LIP5 is expressed as a 42 kDa protein in all mouse tissues tested. Alternatively-spliced gene products could not be detected. Immunohistochemical studies revealed that in tissues positive for LIP5, LIP5 is detected in virtually all epithelial cells of the examined rodent and human tissues. The observed LIP5 expression in epithelial tissues suggests that LIP5 is of particular importance in the MVB sorting and degradation of proteins expressed in polarized cells. PMID- 20358265 TI - Predictors of hepatitis knowledge improvement among methadone maintained clients enrolled in a hepatitis intervention program. AB - This randomized, controlled study (n = 256) was conducted to compare three interventions designed to promote hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination completion, among clients undergoing methadone maintenance treatment (MMT) in Los Angeles and Santa Monica. The participants were randomized into three groups: Motivational Interviewing-Single Session (MI-Single), Motivational Interviewing-Group (MI-Group), or Nurse-Led Hepatitis Health Promotion (HHP). All three treatment groups received the 3-series HAV/HBV vaccine. The MI sessions were provided by trained therapists, the Nurse-Led HHP sessions were delivered by a research nurse. The main outcome variable of interest was improvement in HBV and HCV knowledge, measured by a 6-item HBV and a 7-item HCV knowledge and attitude tool that was administered at baseline and at 6 month follow-up. The study results showed that there was a significant increase in HBV- and HCV-related knowledge across all three groups (p < 0.0001). There were no significant differences found with respect to knowledge acquisition among the groups. Irrespective of treatment group, gender (P = 0.008), study site (P < 0.0001) and whether a participant was abused as a child (P = 0.017) were all found to be predictors of HCV knowledge improvement; only recruitment site (P < 0.0001) was found to be a predictor of HBV knowledge. The authors concluded that, although MI-Single, MI-Group and Nurse-Led HHP are all effective in promoting HBV and HCV knowledge acquisition among MMT clients, Nurse-Led HHP may be the method of choice for this population as it may be easier to integrate and with additional investigation may prove to be more cost efficient. PMID- 20358266 TI - Impact of neighborhood racial composition and metropolitan residential segregation on disparities in breast cancer stage at diagnosis and survival between black and white women in California. AB - We examined the impact of metropolitan racial residential segregation on stage at diagnosis and all-cause and breast cancer-specific survival between and within black and white women diagnosed with breast cancer in California between 1996 and 2004. We merged data from the California Cancer Registry with Census indices of five dimensions of racial residential segregation, quantifying segregation among Blacks relative to Whites; block group ("neighborhood") measures of the percentage of Blacks and a composite measure of socioeconomic status. We also examined simultaneous segregation on at least two measures ("hypersegregation"). Using logistic regression we examined effects of these measures on stage at diagnosis and Cox proportional hazards regression for survival. For all-cause and breast-cancer specific mortality, living in neighborhoods with more Blacks was associated with lower mortality among black women, but higher mortality among Whites. However, neighborhood racial composition and metropolitan segregation did not explain differences in stage or survival between Black and White women. Future research should identify mechanisms by which these measures impact breast cancer diagnosis and outcomes among Black women. PMID- 20358267 TI - Further opportunities for cost reduction of medical care. AB - The already high and still rising cost of health care has become a matter of serious concern and a subject of political dispute. The problem has no magic cures but, as is shown here, there are a number of promising modifications in current practice that promise to reduce the required outlays without impairing appropriate health care. Continual reports of new medicines, new tests, and new procedures have created an urgent need for careful comparison and evaluation of the advantages and beneficial results that these innovations offer. The same is true for the growing knowledge of genetic variations, which affects the course of therapy for some patients. Costs also can be saved, in some instances, by utilization of medical therapy, rather than interventional procedures. Preventive medicine provides still more opportunities for cost savings. This paper provides an overview of promising potential approaches to reduce the cost of health care. PMID- 20358270 TI - Re: unprepared, understaffed, and unplanned. PMID- 20358271 TI - Prenatal and perinatal risk factors for autism in China. AB - We conducted a case-control study using 190 Han children with and without autism to investigate prenatal and perinatal risk factors for autism in China. Cases were recruited through public special education schools and controls from regular public schools in the same region (Tianjin), with frequency matching on sex and birth year. Unadjusted analyses identified seven prenatal and seven perinatal risk factors significantly associated with autism. In the adjusted analysis, nine risk factors showed significant association with autism: maternal second-hand smoke exposure, maternal chronic or acute medical conditions unrelated to pregnancy, maternal unhappy emotional state, gestational complications, edema, abnormal gestational age (<35 or >42 weeks), nuchal cord, gravidity >1, and advanced paternal age at delivery (>30 year-old). PMID- 20358272 TI - Male gender identity in complete androgen insensitivity syndrome. AB - Women and girls with complete androgen insensitivity syndrome (CAIS) invariably have a female typical core gender identity. In this case report, we describe the first case of male gender identity in a CAIS individual raised female leading to complete sex reassignment involving both androgen treatment and phalloplasty. CAIS was diagnosed at age 17, based on an unambiguously female phenotype, a 46,XY karyotype, and a 2660delT androgen receptor (AR) gene mutation, leading to a premature stop in codon 807. Bilateral gonadectomy was performed but a short period of estrogen treatment induced a negative emotional reaction and treatment was stopped. Since the age of 3, childhood-onset cross gender behavior had been noticed. After a period of psychotherapy, persisting male gender identity was confirmed. There was no psychiatric co-morbidity and there was an excellent real life experience. Testosterone substitution was started, however without inducing any of the desired secondary male characteristics. A subcutaneous mastectomy was performed and the patient received phalloplasty by left forearm free flap and scrotoplasty. Testosterone treatment was continued, without inducing virilization, and bone density remained normal. The patient qualifies as female to-male transsexual and was treated according to the Standards of Care by the World Professional Association for Transgender Health with good outcome. However, we do not believe that female sex of rearing as a standard procedure should be questioned in CAIS. Our case challenges the role of a functional AR pathway in the development of male gender identity. PMID- 20358273 TI - Recreational use of erectile dysfunction medications in undergraduate men in the United States: characteristics and associated risk factors. AB - Mounting evidence indicates that erectile dysfunction medications (EDMs) have become increasingly used as a sexual enhancement aid among men without a medical indication. Recreational EDM use has been associated with increased sexual risk behaviors, an increased risk for STIs, including incident HIV infection, and high rates of concomitant illicit drug use. The aim of the present study was to investigate the characteristics and associated risk factors for recreational EDM use among young, healthy, undergraduate men. A cross-sectional sample of 1,944 men were recruited from 497 undergraduate institutions within the Unites States between January 2006 and May 2007. The survey assessed patterns of EDM use, as well as demographic, substance use, and sexual behavior characteristics. Four percent of participants had recreationally used an EDM at some point in their lives, with 1.4% reporting current use. The majority of recreational EDM users reported mixing EDMs with illicit drugs and particularly during risky sexual behaviors. Recreational EDM use was independently associated with increased age, gay, or bisexual sexual orientation, drug abuse, lifetime number of sex partners, and lifetime number of "one-night stands." Recreational EDM users also reported a 2.5-fold rate of erectile difficulties compared to nonusers. Overall, recreational use of EDMs was associated with sexual risk behaviors and substance abuse; however, a relatively small proportion of undergraduates reported using EDMs. Results also suggest that a sizable portion of recreational EDM users are heterosexual men, and that use does not solely occur within the environments of venues that cater to men having sex with men. PMID- 20358274 TI - A behavioral decision model testing the association of marijuana use and sexual risk in young adult women. AB - We created a model conceptualizing sexual risk as a series of discrete event specific behavioral decisions and tested the hypothesis that marijuana use was associated with increased sexual risk-taking. Three hundred eight marijuana-using women aged 18-24 completed a 90-day time-line-follow-back to assess sexual behaviors and marijuana use. A sequential logit model estimated the effect of marijuana use on the likelihood of being sexually active, partner type when sexually active, and condom nonuse conditional on partner type. Participants had a mean age of 20.4 years, with 67% Caucasian. Marijuana use was associated with an increased likelihood of being sexually active (OR 1.6; 95% CI 1.33, 1.93) and with condom nonuse when sexually active with casual partners (OR 2.58; 95% CI 1.1, 6.09). This behavioral decision model identified where marijuana use affected sexual risk, and suggests where interventions designed to reduce risk may have an impact. PMID- 20358275 TI - Genome-wide microarray evidence that 8-cell human blastomeres over-express cell cycle drivers and under-express checkpoints. AB - PURPOSE: To understand cell cycle controls in the 8-Cell human blastomere. METHODS: Data from whole human genome (43,377 elements) microarray analyses of RNAs from normal 8-Cell human embryos were compiled with published microarrays of RNAs from human fibroblasts, before and after induced pluripotency, and embryonic stem cells. A sub database of 3,803 genes identified by high throughput RNA knock down studies, plus genes that oscillate in human cells, was analyzed. RESULTS: Thirty-five genes over-detected at least 7-fold specifically on the 8-Cell arrays were enriched for cell cycle drivers and for proteins that stabilize chromosome cohesion and spindle attachment and limit DNA and centrosome replication to once per cycle. CONCLUSIONS: These results indicate that 8-cell human blastomere cleavage is guided by cyclic over-expression of key proteins, rather than canonical checkpoints, leading to rapidly increasing gene copy number and a susceptibility to chromosome and cytokinesis mishaps, well-noted characteristics of preimplantation human embryos. PMID- 20358278 TI - Developing and improving after-school programs to enhance youth's personal growth and adjustment: a special issue of AJCP. AB - Participating in after-school programs (ASPs) has become a common experience for children. This special issue provides a perspective on the current status of research on ASPs. This introductory article overviews the historical and current context of ASPs and then describes a developmental ecological model to guide research in this area. The model offers a framework from which to organize and synthesize the research presented in this issue. Key principles include a holistic view of development that recognizes interrelations between multiple domains of youth adjustment, attention to multiple, relevant factors within and outside of youth that affect development, examining the dynamic interplay between persons, program features, and other contexts over time, and understanding the active role of youth in affecting their own development. These principles are examined in relation to five main areas: youth characteristics, social ecologies, program features, participation, and short- and long-term outcomes. Recommendations for future research are discussed. PMID- 20358276 TI - Embryo selection criteria based on morphology VERSUS the expression of a biochemical marker (sHLA-G) and a graduated embryo score: prediction of pregnancy outcome. AB - PURPOSE: To compare pregnancy and implantation rates when embryos are selected based on a single Day 3 (D 3) morphology score vs. a GES score plus sHLA-G expression. METHODS: A prospective randomized study (n = 214) undergoing fresh ICSI cycles. Embryos were selected for transfer based on either Day 3 morphology score (Group A) or GES-scoring plus sHLA-G expression (Group B). RESULTS: Clinical [35/107 (33%) vs. 52/107 (49%)] and ongoing pregnancy [20/107 (19%) vs. 52/107 (49%)] rates were significantly different between Group A and Group B (p < 0.05). Implantation rates were not significantly different between Group A [52/353 (15%)] and Group B [73/417 (18%)] (p < 0.05). The number of pregnancies lost during the first trimester was nearly 12 times higher in Group A [25/52 (48%)]. CONCLUSION: The miscarriage rate was significantly lower in Group B than Group A and the pregnancy results were superior when embryos were selected based on GES plus sHLA-G expression. PMID- 20358279 TI - COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients. AB - In breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated with primary surgery between 1985 and 1994 and explained the variable results of COX2 expression found in the literature. A tissue microarray was constructed of available tumour material, and ER, PgR, HER2, Ki67 and COX2 were examined by immunohistochemistry. Median follow-up was 19 years. Fifty-five percent (n = 369/677) of patients received no systemic treatment. COX2 was scored using a weighted histoscore. Analysis of COX2 expression in two groups based on the median (148; below vs. above) showed an increased hazard ratio (HR) of 1.35 (95% CI 1.05-1.75, P = 0.021) for disease free survival (DFS) and of 1.39 (95% CI 1.03-1.82, P = 0.016) for overall survival (OS). However, COX2 did not remain independent in multivariate analysis. In patients with hormone receptor positive tumours, COX2 expression had a negative influence on outcome (low vs. high: DFS: HR 1.37, 95% CI 1.07-1.76, P = 0.013). This effect disappeared when endocrine therapy was administered (low vs. high: DFS: HR 0.93, 95% CI 0.51-1.70, P = 0.811) while it remained statistically significant when endocrine therapy was omitted (low vs. high: DFS: HR 1.48, 95% CI 1.12-1.94, P = 0.005). Our results show that COX2 plays a role in hormonal pathways. Our results can explain the results found in previously published studies. PMID- 20358280 TI - Longitudinal aggregate data model-based meta-analysis with NONMEM: approaches to handling within treatment arm correlation. AB - Literature data are often reported as multiple (longitudinal) mean outcomes observed in several groups of patients within a study. Observations within a study are correlated because the patients come from a common population, and the mean observations over time within a treatment arm are correlated because they are based on the same set of patients. As a result, model-based meta-analysis may require more than two levels of random effects to correctly characterize this correlation structure. Using simulation, we explored and evaluated ways to implement multi-level random effects in NONMEM. Simulation models that were linear and non-linear in the random effects were investigated. We compared estimation models that included study and/or treatment arm-level random effects, with and without residual correlation. With all estimation strategies, the fixed random effects parameters were accurately estimated. With regard to correctly characterizing the variability, models that accounted for correlation within a study and treatment arm over time were the best in some situations, while models that accounted for study-level correlation only were better in others. Models that included only treatment arm-level random effects were not superior in any scenario. PMID- 20358281 TI - The fluorescence properties and lifetime study of G-quadruplexes single- and double-labeled with pyrene. AB - We report steady state fluorescence and lifetime emission studies of d(GGTTGGTGTGGTTGG) (TBA) and d(GGGTTAGGGTTAGGGTTAGGG) (Htelom) oligonucleotides labeled with pyrene through a 3-aminopropyl linker. Such G-rich sequences are able to self-assemble into G-quadruplexes, especially in the presence of specific cations like potassium. A comparative studies with single- and double-labeled G quadruplexes were carried out. For each probe we have measured fluorescence decays for emission wavelength of 390 and 480 nm in the varying concentration of potassium ion. We have calculated average lifetimes for every system as well as the fractional distribution alpha(i) of emitting species. PMID- 20358282 TI - Spectrometric studies on the sonodynamic damage of protein in the presence of levofloxacin. AB - Taking bovine serum albumin (BSA) as typical molecules, the sonodynamic damage of protein in the presence of Levofloxacin (LVFX) and its mechanism were studied by fluorescence and UV-vis spectra. Various influencing factors such as ultrasonic irradiation time, pH value, ionic strength and solution temperature on the damage of BSA were also discussed. The results showed that ultrasound can enhance the damage of LVFX on BSA. The damage degree of BSA was aggravated with the increase of ultrasonic irradiation time, solution temperature and ionic strength, whereas decreased with the increase of solution pH value. Furthermore, the reactive oxygen species (ROS) in reaction system were studied by oxidation and extraction photometry. Experimental results showed that the amounts of superoxide anion radical (.O(2)(-)) and hydroxyl radical (.OH) were significantly more than that of singlet oxygen ((1)O(2)) in the presence of LVFX under ultrasonic irradiation. PMID- 20358284 TI - Diazepam fluorimetric monitoring upon photo-degradation in an automatic miniaturized flow system. AB - The present work describes the fully integration in line of a photo-degradation unit, comprising a low pressure UV lamp, in a Multipumping Flow System (MPFS), for the fluorimetric chemical control of commercially available pharmaceutical formulations containing diazepam. The utilization of an organized micellar medium provided enhanced fluorescence emission. The results allowed to obtain a linear working range for diazepam concentrations of up to 40 mg L(-1) (r = 0.9998) and the detection limit was about 0.97 mg L(-1). The results obtained by the miniaturized and automatic flow system were in agreement with those furnished by the reference procedure, with relative deviations comprised between -2.09% and 2.13%. PMID- 20358285 TI - Biochemical characterization of Candida albicans alpha-glucosidase I heterologously expressed in Escherichia coli. AB - Protein glycosylation is one of the most common post-translational modifications present in the eukaryotic cell. The N-linked glycosylation is a biosynthetic pathway where an oligosaccharide is added to asparagine residues within the endoplasmic reticulum. Upon addition of the N-linked glycan to nascent proteins, alpha-glucosidase I removes the outermost alpha1,2-glucose unit from the N-linked core Glc(3)Man(9)GlcNAc(2). We have previously demonstrated that the endoplasmic reticulum alpha-glucosidase I is required for normal cell wall composition, and virulence of the human pathogen Candida albicans. In spite of the importance of this enzyme for normal cell biology, little is known about its structure and the amino acids participating in enzyme catalysis. Here, a DNA fragment corresponding to the 3'-end fragment of C. albicans CWH41, the encoding gene for alpha glucosidase I, was expressed in a bacterial system and the recombinant peptide showed alpha-glucosidase activity, despite lacking 419 amino acids from the N terminal end. The biochemical characterisation of the recombinant enzyme showed that presence of hydroxyl groups at carbons 3 and 6, and orientation of hydroxyl moiety at C-2 are important for glucose recognition. Additionally, results suggest that cysteine rather than histidine residues are involved in the catalysis by the recombinant enzyme. PMID- 20358286 TI - Inactivation and sub-lethal injury of Escherichia coli in a copper water storage vessel: effect of inorganic and organic constituents. AB - This study provides information on the effects of inorganic and organic constituents on inactivation and sub-lethal injury of Escherichia coli in water stored in a copper vessel. E. coli suspensions were stored for up to 24 h in copper vessels containing one of the following dissolved constituents at 1 g/l: salts of inorganic ions, carbohydrates, proteins and complex natural organic mixtures. Samples were surface plated onto (i) nutrient agar, incubated under standard aerobic conditions to provide conventional counts for uninjured bacteria count and onto (ii) nutrient agar plates with 0.5 g/l sodium pyruvate incubated under anaerobic conditions to enumerate sub-lethally injured (oxygen-sensitive) bacteria alongside their healthy counterparts. The concentration of dissolved copper in the stored water was determined using atomic absorption spectrophotometry. The addition of chloride salts resulted in a faster inactivation of E. coli compared to pure water with no dissolved additives, irrespective of the counterion. In contrast, a slower inactivation was observed in the presence of Na(2)SO(4), NaNO(3) and NaNO(2) when compared to NaCl. Addition of the carbohydrates glucose, lactose and starch gave broadly similar results to those obtained using unsupplemented water. However, the addition of amino acids, proteins, humic acid or complex organic mixtures caused a dramatic decrease in inactivation of E. coli, with evidence of a greater number of sub lethally injured bacteria than was seen with other added constituents. The amount of copper was highest in stored water containing amino acids and complex organic constituents, with the slow inactivation most likely to be due to complex formation between leached copper and these organic constituents. The present study clearly demonstrates that water composition, particularly natural organic constituents, has a substantial impact on the antibacterial effectiveness and dissolved copper concentration of water stored in copper vessels and that both aspects will need to be considered in terms of their impact on the practical use of copper-based systems for small-scale water treatment. PMID- 20358283 TI - The concept of lambda-ratiometry in fluorescence sensing and imaging. AB - Very limited number of parameters is available for fluorescence sensing and imaging. The changes of intensity are of low analytical value due to the absence of internal reference. Anisotropy and lifetime sensing have their own limitations. In this respect the lambda-ratiometric (based on intensity ratios at two or more wavelengths) recording of spectral changes becomes more popular. Because the spectral changes are connected directly with the variations of interaction energies this approach is seen as the most universal method to study intermolecular interactions. It is applicable for different sensor formats and for obtaining analytical information from cell images. Here we critically analyze different approaches in lambda-ratiometric sensing that use single and double fluorescence emitters and are based on different mechanisms producing spectroscopic change. Very promising is the exploration of mechanisms that allow obtaining ratiometric response from a single dye. PMID- 20358287 TI - Studying implementation quality of a school-based prevention curriculum in frontier Alaska: application of video-recorded observations and expert panel judgment. AB - This study assesses the implementation quality of Think Smart, a school-based drug prevention curriculum that was designed to reduce use of harmful legal products (HLPs; e.g., inhalants and over-the-counter drugs), alcohol, tobacco, and other drugs among 5th- and 6th-grade students in frontier Alaska. Participating in the study were eight communities that took part in a larger randomized control trial to assess the short-term effects of the Think Smart curriculum. Video-recorded observations of the 12 core and 3 booster lessons were conducted in 20 classrooms. Ninety-five sessions were randomly selected from 228 usable videodiscs, and two pairs of researchers observed each video recording to code level of dosage, adherence to curriculum design, and teachers' delivery skills. Inter-rater reliability for all implementation quality measures was very high. An expert panel consisting of 16 scientists reviewed the results of the implementation study and concluded that the level of dosage and adherence to the curriculum design was at least as high as those yielded by similar studies. However, the panel assessed the delivery quality to be only marginal in comparison to results of other studies. The experts concluded that the implementation quality of the Think Smart curriculum was adequate even though the teachers' delivery skills were only marginal. A bootstrapping analysis, in which 1,000 samples were drawn for each implementation quality result, found the expert judgments to be reliable. The authors conclude that despite some limitations, video-recorded observations, as well as expert judgment, provide strong methodologies that should be considered for future implementation quality studies. PMID- 20358288 TI - Phospholipid Polymer Biointerfaces for Lab-on-a-Chip Devices. AB - This review summarizes recent achievements and progress in the development of various functional 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer biointerfaces for lab-on-a-chip devices and applications. As phospholipid polymers, MPC polymers can form cell-membrane-like surfaces by surface chemistry and physics and thereby provide biointerfaces capable of suppressing protein adsorption and many subsequent biological responses. In order to enable application to microfluidic devices, a number of MPC polymers with diverse functions have been specially designed and synthesized by incorporating functional units such as charge and active ester for generating the microfluidic flow and conjugating biomolecules, respectively. Furthermore, these polymers were incorporated with silane or hydrophobic moiety to construct stable interfaces on various substrate materials such as glass, quartz, poly(methyl methacrylate), and poly(dimethylsiloxane), via a silane-coupling reaction or hydrophobic interactions. The basic interfacial properties of these interfaces have been characterized from multiple aspects of chemistry, physics, and biology, and the suppression of nonspecific bioadsorption and control of microfluidic flow have been successfully achieved using these biointerfaces on a chip. Further, many chip-based biomedical applications such as immunoassays and DNA separation have been accomplished by integrating these biointerfaces on a chip. Therefore, functional phospholipid polymer interfaces are promising and useful for application to lab-on-a-chip devices in biomedicine. PMID- 20358289 TI - Retro-convection enhanced drug delivery: a computational study. AB - Retro-convection enhanced delivery (R-CED) is an emerging drug delivery method to overcome the blood brain barrier (BBB). We have developed a mathematical model to understand the fluid flow and mass transfer in the interstitium of brain tissue in R-CED therapy. The model was used to predict pressure distributions, fluid flow patterns, and drug concentration profiles. Some numerical results were obtained by computer simulations. Three kinds of microdialysis membranes used in R-CED protocols were analyzed in detail. While fluid flow was independent of the choice of membranes, mass transfer processes and drug distributions were found to be highly dependent on the choice of membranes. Sensitivity analysis on a variety of parameters and over a wide range of parameter values was carried out. Although R-CED turned out to be efficacious in generating fluid flows within the brain tissue, it did not favor a large effective treatment volume and needed to be re examined and re-evaluated experimentally. PMID- 20358290 TI - Prediction of sphingosine 1-phosphate-stimulated endothelial cell migration rates using biochemical measurements. AB - The ability to predict endothelial cell migration rates may aid in the design of biomaterials that endothelialize following implantation. However, the complexity of the signaling response to migration-promoting stimuli such as sphingosine 1 phosphate (S1P) makes such predictions quite challenging. A number of signaling pathways impact S1P-mediated cell migration, including the Akt and Src pathways, which both affect activation of the small GTPase Rac. Rac activation promotes the formation of lamellipodia, and thus should be intimately linked to cell migration rates. In immortalized endothelial cells, expression of proteins that inhibit Akt, Src, and Rac (PTEN, CSK, and beta2-chimaerin, respectively) was decreased using RNA interference, resulting in increases in the basal level of activation of Akt, Src, and Rac. Cells were scrape-wounded and stimulated with 1 microM S1P. The timecourse of Akt, Src, and Rac activation was followed over 2 h in the perturbed cells, while migration into the scrape wound was measured over 6 h. Rac activation at 120 min post-stimulation was highly correlated with the mean migration rate of cells, but only in cells stimulated with S1P. Using partial least squares regression, the migration rate of cells into the scrape wound was found to be highly correlated with the magnitude of the early Akt peak (e.g., 5 15 min post-stimulation). These results demonstrated that biochemical measurements might be useful in predicting rates of endothelial cell migration. PMID- 20358291 TI - Positron emission tomography; viable tool in patients pre-CABG? PMID- 20358292 TI - A GA-insensitive dwarf mutant of Brassica napus L. correlated with mutation in pyrimidine box in the promoter of GID1. AB - A dwarf mutant from Brassica napus, namely NDF-1, which was derived from a high doubled haploid (DH) line '3529'(Brassica napus L.) of which seeds were jointly treated with chemical inducers and fast neutron bombardment, was revealed that dwarfism is under the control of a major gene(designated as ndf1) with a mainly additive effect and non-significant dominance effect. The germination and hypocotyls elongation response of dwarf mutants after exogenous GA and uniconazol application showed NDF-1 was a gibberellin insensitive dwarf. We cloned the Brassica napus GID1 gene, named BnGID1, and found it was the ortholog of AtGID1a. The sequence blasting of the BnGID1 genes from NDF-1 and wild type showed there was no mutant in the gene. But the quantitative RT-PCR analysis of GID1 EST pointed out the mutation was caused by the low-level expression of BnGID1 gene. After sequenced the BnGID1 gene's upstream, we found three bases mutated in the pyrimidine box (P-box) of the BnGID1 promoter, which is linkage with the dwarf mutant. PMID- 20358294 TI - Assessment of protozoa in Yunnan Yellow cattle rumen based on the 18S rRNA sequences. AB - Library of ruminal protozoal 18S rRNA of Yunnan Yellow Cattle has been constructed in the present study. Phylogenic analysis of sequences was meanwhile employed to reveal the diversity of protozoa in the rumen of Yunnan Yellow Cattle. One Yellow Cattle was fed malt meal (YCRPB) and the other was fed wheat straw (YCRPS). A protozoa-specific primer (P-SSU-342f) and a eukarya-specific primer (Medlin B) were used to amplify a 1,360-bp fragment of DNA encoding protozoal small subunit (SSU) ribosomal RNA from rumen fluid. The results showed as follows: A total of 121 clones were obtained and fell into four genera identified as Entodinium (66.9%), Dasytricha (5.8%), Isotricha (9.1%), and Diplodinium (18.2%). Within the genus Entidinium, 48 of the YCRPB sequences and 33 of the YCRPS sequences clustered with the Entodinium caudatum. 7 of the YCRPB sequences were phylogenetically placed within the genus Dasytricha. 11 of the YCRPB sequences were related with high confidence to Isotricha intestinalis. 22 of the YCRPS sequences were phylogenetically placed within the genus Diplodinium. The predominant protozoal genus identified in the rumen fluid belonged to the Entodinium group, and the divergences between two cattle may due to diet and individual differences. PMID- 20358293 TI - TWEAK as a target for therapy in systemic lupus erythematosus. AB - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Through activation of the fibroblast growth factor-inducible 14 (Fn14) receptor, TWEAK regulates cell proliferation, cell death and inflammation. The available evidences have indicated that TWEAK might be a target for therapeutic intervention in renal, vascular injury and neuropathy. Since renal, vascular and neuropsychiatric complications are frequently encountered in systemic lupus erythematosus (SLE)--a systemic autoimmune disease, TWEAK-Fn14 pathway may be implicated in the pathogenesis of SLE. In this review, we will discuss the TWEAK-Fn14 pathway and the therapeutic potential of modulating this pathway in SLE. PMID- 20358295 TI - Molecular analysis of a UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT) gene from purple potato (Solanum tuberosum). AB - In anthocyanin biosynthesis, UDP-glucose: anthocyanidin 3-O-glucosyltransferase (UFGT) catalyzes the transfer of the glucosyl moiety from UDP-glucose to the 3 hydroxyl group of anthocyanidins, producing the first stable anthocyanins. The full-length cDNA of UFGT (designated as StUFGT) was isolated and characterized from Solanum tuberosum. The full-length cDNA of StUFGT was 1536 bp containing a 1344 bp open reading frame (ORF) encoding 448 amino acids with a calculated molecular mass of 49.9 kDa and an isoelectric point of 5.62. Comparative and bioinformatic analyses revealed that StUFGT has extensive homology with UFGTs from other plant species. Phylogenetic analysis indicates that StUFGT belongs to the plant UFGT cluster. StUFGT was found to be expressed in roots, stems, leafstalks and leaves. Expression profiling analysis revealed that StUFGT expression was induced correspondingly by exogenous elicitors including gibberellic acid and sucrose, suggesting that UFGT might play a regulatory role in anthocyanin biosynthesis in Solanum tuberosum at the transcriptional level. PMID- 20358296 TI - Characterization of peptidoglycan hydrolase in Cag pathogenicity island of Helicobacter pylori. AB - The Cag Type IV secretion apparatus proteins in Helicobacter pylori can mediate the injection of effector CagA protein into eukaryotic target cells. Although this apparatus forms an important pathway for bacterium-host interaction, its assembly process in vivo is poorly understood, and the proteins which contribute to break the bacterial cell walls in Cag-PAI have not yet been identified. The caggamma gene in Cag-PAI is a unique member that contains a conserved SLT catalysis domain, which makes it an attracting question whether cagy gene has the capacity to digest the bacterial cell wall. In the current study, therefore, the caggamma gene was cloned from the H. pylori NCTC 11637 and expressed in Escherichia coli, and its lytic effect on cell walls in vitro was observed. Results indicated that Caggamma protein has a lytic activity against bacterial cell walls. An allelic-exchange mutant (Deltacaggamma) was further constructed to investigate the relationship between Caggamma and effector CagA translocation. These results suggested that Caggamma contributed to the assembly of Cag Type IV secretion apparatus by digesting the peptidoglycan meshwork of bacterial cell walls. PMID- 20358297 TI - ARLTS1, MDM2 and RAD51 gene variations are associated with familial breast cancer. AB - Genetic factors that contribute to the risk of breast cancer are largely not known and association studies have revealed several genes with low penetrance risk alleles for breast cancer. Analysis of these genes may provide important information on the risk factors affecting carcinogenesis. Variations in the ARLTS1, RAD51 and MDM2 genes have been associated with increased risk of different cancer types but for breast cancer the results are not consistent. In this study we investigated the role of the allelic variants in candidate genes acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease. Presence of the polymorphic variants were investigated by amplification of the corresponding regions and restriction fragment length polymorphism analysis. Genotype and allele frequencies in the patients were significantly different for all three variants. Our results indicate that the polymorphic variants might affect individual susceptibility towards breast cancer. PMID- 20358298 TI - The mRNA of lipin1 and its isoforms are differently expressed in the longissimus dorsi muscle of obese and lean pigs. AB - Lipin1 has been documented to play an important role in adipogenesis. In the present study, the mRNA expression level of lipin1 and its isoforms in longissimus dorsi muscle were determined by semi-quantification RT-PCR in lean PIC and obese Rongchang pigs. Further, we determined mRNA expression for lipin1 and its two isoforms in Rongchang obese pigs which had either a high or low intramuscular fat content. We demonstrate for the first time that porcine lipin1 has two alternative forms, lipin-alpha and lipin-beta. Unlike mice and humans where the lipin-beta has 99 more nucleotides than lipin-alpha, we found that in swine, lipin-beta has 108 more nucleotides than lipin-alpha. Our results indicate that the longissimus dorsi muscle of Rongchang obese pigs have a higher level of mRNA expression for lipin1 and its isoforms than PIC lean pigs. Furthermore, Rongchang pigs with higher intramuscular fat content had a higher lipin1 and lipin-beta mRNA expression in longissimus dorsisi muscle than Rongchang pigs with lower intramuscular fat content (P<0.05), whereas no difference was seen in lipin alpha mRNA expression between Rongchang pigs with high or low intramuscular fat. The ratio of lipin-beta mRNA to lipin-alpha mRNA was also significantly different between Rongchang pigs distinguished by a high intramuscular fat content compared with those with low intramuscular fat (P<0.05). These data suggested that the lipin1 gene may have a crucial effect on body lipid accumulation in pigs, whereas the lipin-beta isoform may play an important role in intramuscular fat deposition in obese pigs. PMID- 20358299 TI - Quality of life after the menopause in Iran: a population study. AB - OBJECTIVE: Quality of life (QoL) decreases after the menopause as it has been assessed by several designed tools. The aim of the present research was to assess QoL and determine factors related to its impairment among postmenopausal Iranian women. METHODS: This cross-sectional study was conducted through cluster sampling among 480 postmenopausal women in Yazd, Islamic Republic of Iran, in 2008. Data were collected using the menopause quality of life questionnaire (MENQOL) by interviewing. Content validity and Cronbach's alpha were used, respectively, to ensure the validity and reliability of the questionnaires. Inferential and descriptive statistics via SPSS.15 software was used for data analysis. RESULTS: The results showed that the menopausal women have worse QoL scores in vasomotor dimension and higher QoL scores in physical dimension. Univariate analysis showed that there were significant differences in the MENQOL scores by age, number of children, education, postmenopausal stage, employment status, and BMI. Women aged 60-65 (P < 0.05), with a university level of education (P < 0.01), who had employment (P < 0.01), who had postmenopausal stage 5 or more years (P < 0.05), with a body mass index or=5 increased the risk for higher scores within the sexual domain, respectively. CONCLUSION: Menopause causes a decrease in quality of life, which is dependent to work and other socio-demographic variables. Therefore, it is necessary to develop effective intervention programs to improve quality of life after menopause. PMID- 20358301 TI - The clinical significance of vimentin-expressing gastric cancer cells in bone marrow. AB - BACKGROUND: Expression of the mesenchymal marker gene vimentin (VIM) in gastric cancer is associated with a more aggressive form of the disease and poor prognosis. Because epithelial mesenchymal transition (EMT) plays a critical role in the progression of gastric cancer, VIM expression was examined in the bone marrow (BM) of gastric cancer patients. METHODS: BM samples from 437 gastric cancer patients were collected and analyzed by quantitative RT-PCR. Expression of VIM protein in the primary lesions of resected gastric cancers was evaluated using immunohistochemistry. Furthermore, induction of VIM expression by TGF-beta1 and hypoxia was evaluated in gastric cancer cells. RESULTS: VIM mRNA expression increased concordantly with clinical staging and was significantly associated with tumor invasion and lymph node metastasis (P < .0001). Though cancer cells in the primary lesions did not stain with VIM antibody, some of the cells invading the intratumoral vessels were strongly positive for VIM, but were negative for E cadherin. Hypoxic conditions and treatment with TGF-beta1 induced VIM expression and repressed E-cadherin in gastric cancer cells, coupled with an alteration of cellular morphology. CONCLUSIONS: We found that gastric cancer cells undergo EMT in BM to survive and metastasize. These findings suggest that isolated tumor cells have the potential to undergo EMT, which could increase the malignancy of gastric cancer. PMID- 20358300 TI - Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction. AB - BACKGROUND: Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. MATERIALS AND METHODS: Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy-Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed preprocedure and at 1 and 4 weeks following PBD. RESULTS: A total of 109 (60 male/49 female) patients enrolled; 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were 2 procedure-related deaths. All-cause mortality was 10% (N = 11) at 4 weeks and 28% (N = 31) at 8 weeks post-PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P < .01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P < .01). CONCLUSIONS: PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population. PMID- 20358302 TI - The effect of low molecular weight heparin thromboprophylaxis on bleeding complications after gastric cancer surgery. AB - BACKGROUND: Low molecular weight heparin (LMWH) has been widely used to prevent venous thromboembolism in cancer surgical patients. However, relatively few studies have examined the safety aspects related to the use of LMWH after abdominal cancer surgery. This study was designed to investigate the relationship between bleeding complications and LMWH thromboprophylaxis after gastric cancer surgery. METHODS: From March to July in 2009, 179 consecutive patients who underwent gastric cancer surgery at our institution were administered LMWH (3200 U once daily from 2 to 6 h before surgery until discharge) perioperatively. A total of 182 patients consecutively treated before the introduction of LMWH prophylaxis were selected as controls. RESULTS: There were 234 men and 127 women (mean age, 60 +/- 12 years). No significant intergroup differences were observed with respect to clinicopathological features and operative procedures. No patient in the LMWH or control group developed symptomatic venous thromboembolism postoperatively. However, the LMWH group had a significantly higher surgical complication rate (27.4 versus 15.4%, P = 0.005). Among the surgical complications, postoperative bleeding and wound complications were significantly higher in the LMWH group, whereas other complications were similar in the two study groups. Multivariate analysis showed that LMWH administration was an independent risk factor (odds ratio, 2.83; 95% confidence interval, 1.28-6.23, P = 0.009) of postoperative bleeding. CONCLUSIONS: LMWH thromboprophylaxis was found to increase significantly the risk of bleeding complications after gastric cancer surgery. Optimal LMWH prophylaxis regimens, including the dosage and timing of treatment commencement, for gastric cancer surgery should be determined in further clinical trials. PMID- 20358303 TI - Effective mental health consumer education: a preliminary exploration. AB - People with serious mental illnesses are increasingly becoming more active participants in their treatment and recovery. At times, their participation may be limited by incomplete, unclear, or insufficient information. The authors used a grounded theory approach to look at the unmet informational needs described by consumers. Participants in this study called for materials appropriate to their level of understanding, assistance with interpreting and comprehending information when necessary, and information on policies that affect the treatment they receive. Ultimately, an informed consumer is one empowered to make decisions about the course of his or her recovery and participate meaningfully in the patient-provider relationship. PMID- 20358304 TI - A mathematical method for constraint-based cluster analysis towards optimized constrictive diameter smoothing of saphenous vein grafts. AB - This study was concerned with the cluster analysis of saphenous vein graft data to determine a minimum number of diameters, and their values, for the constrictive smoothing of diameter irregularities of a cohort of veins. Mathematical algorithms were developed for data selection, transformation and clustering. Constrictive diameter values were identified with interactive pattern evaluation and subsequently facilitated in decision-tree algorithms for the data clustering. The novel method proved feasible for the analysis of data of 118 veins grafts, identifying the minimum of two diameter classes. The results were compared to outcome of a statistical recursive partitioning analysis of the data set. The method can easily be implemented in computer-based intelligent systems for the analysis of larger data sets using the diameter classes identified as initial cluster structure. PMID- 20358305 TI - Psychiatric symptoms and HPA axis function in adolescent methamphetamine users. AB - Methamphetamine (METH) is a widely abused drug. However, little is known about the effects of chronic METH consumption on HPA axis function and psychiatric symptomatology in adolescent METH users. The current study evaluated psychiatric symptoms and changes in the stress response of adolescent METH users. Forty-one adolescent METH users and 75 comparison subjects in the same age range (ages 12 23 years) were recruited. Each subject completed the Symptom Checklist-90R (SCL 90) and was evaluated using the Brief Psychiatric Rating Scale. In addition, the subjects completed the Trier Social Stress Test (TSST) and had salivary cortisol levels measured 30 min before, immediately after, and 60 min after the TSST. Adolescent METH users showed greater severity of symptoms across all measures of the SCL-90. Younger female METH users had the most symptoms. Furthermore, the METH users exhibited significantly enhanced cortisol levels immediately following the TSST (+31%, p = 0.03). Adolescent METH use is associated with greater psychiatric symptoms and enhanced cortisol secretion following a social stressor, particularly in younger female METH users. The psychiatric symptoms may reflect altered prefrontal cortical function resulting from chronic stress/drug use and the resulting glucocorticoid exposure. The results further suggest that treatment approaches should focus on stress-coping strategies to decrease the probability of relapse. PMID- 20358306 TI - Alcohol absorption modification after a laparoscopic sleeve gastrectomy due to obesity. AB - BACKGROUND: The different bariatric surgery techniques that alter the digestive anatomy also modify the gastric absorption surface. Since alcohol is a substance that is mainly metabolized in the stomach, the goal of this study was to determine alcohol absorption before and after a laparoscopic sleeve gastrectomy (LSG) in the same patients. METHODS: Studies were carried out on 12 morbidly obese patients who underwent a LSG (eight men and four women). Each patient was given 3.6 ml of red wine to drink at 14% for each liter of body water mass. Alcotest values (Alcoscan Alcomate AL-6000) were measured 10 min after the wine dose had been consumed. Measurements were then repeated every 5 min until the alcohol had been completely eliminated from the bloodstream. During the postoperatory period (median of 2.3 months), the measurement was repeated with the total dose per kg adjusted to the new water body mass. The results were measured with a nonparametric analysis for repeated samples. RESULTS: The maximum average peak of the Alcotest was 2.02 g/l during the postoperative period compared to 0.87 g/l during the preoperative period (p = 0.001 Wilcoxon). At 175 min, the blood alcohol level value reaches zero (0) in all pre-operatory patients, while after surgery, an average value of 0.26 g/l was observed (p = 0.027 Wilcoxon). After 4 h, an Alcotest average of 0.20 g/l was observed in these patients. CONCLUSION: Alcohol absorption was considerably modified after LSG with higher and longer blood alcohol values for equivalent amounts of alcohol. PMID- 20358307 TI - Collision/reaction cell ICP-MS with shielded torch and sector field ICP-MS for the simultaneous determination of selenium isotopes in biological matrices. AB - The determinations of selenium isotopes in biological samples were performed using both inductively coupled plasma collision/reaction cell quadruple mass spectrometer (CRC-ICP-QMS) and inductively coupled plasma sector field mass spectrometers (SF-ICP-MS). To significantly decrease the argon-based interferences at m/z 74 ((36)Ar(38)Ar), 76 ((38)Ar(38)Ar, (40)Ar(36)Ar), 78 ((38)Ar(40)Ar), and 80 ((40)Ar(40)Ar), the gas-flow rates of a helium and hydrogen mixture used in the collision cell were optimized to 1.0 mL/min H(2) and 3.5 mL/min He. Under the optimized condition, the precisions for natural selenium isotope ratio measurements of both instruments were evaluated and compared using 100 ppb Se standard solution. A modified external calibration quantification method was applied for the simultaneous determination of clinically used enriched selinocompounds ((77)Se-selenate, (82)Se-selenite, (76)Se-methylseleninic acid(IV), (78)Se-methylselenonic acid(VI)) and to examine their fate in rat organs (liver, kidney, and lung). PMID- 20358308 TI - Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats. AB - The synergistic scavenger effects of selenium and melatonin collectively we called Se-Mel was studied on the prevention of neuronal injury induced by ischemia/reperfusion. Male Wistar rats were treated with sodium selenite (0.1 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) 30 min before the middle carotid artery occlusion (MCAO) and immediately after MCAO to male Wistar rats and was continued for 3 days once daily at the interval of 24 h. Behavioral activity (spontaneous motor activity and motor deficit) was improved in Se-Mel-treated rats as compared to MCAO group rats. The level of glutathione and the activity of antioxidant enzymes was depleted significantly while the content of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide radical (NO(.)) was increased significantly in MCAO group. Systemic administration of Se-Mel ameliorated oxidative stress and improves ischemia/reperfusion-induced focal cerebral ischemia. Se-Mel also inhibited inducible nitric oxide synthase expression in Se-Mel+MCAO group as compared to MCAO group rats. Thus, Se-Mel has shown an excellent neuroprotective effect against ischemia/reperfusion injury through an anti-ischemic pathway. In conclusion, we demonstrated that the pretreatment with Se-Mel at the onset of reperfusion, reduced post-ischemic damage, and improved neurological outcome following transient focal cerebral ischemia in male Wistar rat. PMID- 20358309 TI - Acquired hemophagocytic lymphohistiocytosis associated with multiple myeloma. AB - Acquired or secondary hemophagocytic lymphohistiocytosis (sHLH) is a life threatening hyperinflammation syndrome caused mostly by various infectious agents, autoimmune disorders or malignancy. So far, only anecdotal cases of sHLH associated with multiple myeloma have been published. We provide a review of all these reports and include a previously not published case of myeloma-associated sHLH in a 59-year-old male with complex partial epilepsy. Due to aggressive course of sHLH, increased awareness is indicated in all patients with malignancies which develop unremitting fever, cytopenia and splenomegaly. Early diagnosis and immediate introduction of adequate therapy is crucial for the outcome of HLH. PMID- 20358310 TI - A relative value method for measuring and evaluating neonatal cardiac reserve. AB - OBJECTIVE: To devise some indicators for measuring and evaluating the neonatal cardiac reserve by using phonocardiogram test (PCGT). METHODS: Two hundred and thirty one (231) full term and one hundred and fifty four (154) preterm infants participated in this study. The amplitude ratio of the first heart sound to the second heart sound (S1/S2), the ratio of diastolic to systolic duration (D/S) and the cardiac contractility change trend after stimulation (CCCTS) of the neonates were measured, calculated and analyzed. RESULTS: The S1/S2, D/S and CCCTS of full preterm infants were higher than that of preterm infants. The differences of D/S and CCCTS between them were significant (P<0.05). According to the full term neonatal cardiac reserve data, a normal reference range of full term neonatal cardiac reserve was primarily known. CONCLUSION: The indicators S1/S2, D/S and CCCTS may be beneficial for evaluating the neonatal cardiac reserve. We can screen out neonates with reduced cardiac reserve by using the phonocardiogram test. PMID- 20358311 TI - Mutation studies in X-linked myotubular myopathy in three Indian families. AB - Congenital myopathies are a group of genetic disorders characterized by generalised muscle hypotonia and weakness of varying severity. They are distinct entities and do not include muscular dystrophies, metabolic myopathies and mitochondrial disorders. Myotubular myopathy is a rare sub type within this group of disorders. Clinical differentiation of the various types is difficult and requires muscle biopsy with histopathological and immunohistochemical studies for specific diagnosis. Gene studies are a prerequisite for genetic counseling adn prenatal diagnosis. Here presented three cases of X-linked myotubular myopathy in three Indian families where the diagnosis was established by mutation analysis in the MTM1 gene in all, and supported his histopathology in two. All three families had history of previous male neonatal deaths with similar complaints. Molecular analysis revealed hemizygous mutations in the MTM1 gene including c.1261-10A>G in case, 1, c.70C>T (R24X) in case 2, and a previously unreported mutation, c.924_926delCTT(p. F308del), in case 3. Genetic counseling was performed regarding the X-linked inheritance, their 50% risk of recurrence in boys in subsequent pregnancies, and a feasibility of prenatal diagnosis. This is the first report of cases of X-linked myotubular myopathy from India. PMID- 20358312 TI - Effect of improvement of pre-school education through Anganwadi center on intelligence and development quotient of children. AB - OBJECTIVE: To find usefulness of a package of interventions to improve preschool education through Anganwadi centers on psychosocial development of children. METHODS: A case-control study was undertaken to evaluate an intervention. Eight Anganwadi centers were selected using simple random sampling out of sixteen Anganwadi centers in Talegaon PHC area where intervention was done. Ten children in age group of 4-6 years were selected randomly from each of the eight Anganwadi center in intervention arm. For each child from intervention arm, one agematched child was selected from the matched Anganwadi center. For each subject, Intelligence Quotient and Development Quotient were assessed. RESULTS: Mean Development Quotient (DQ) and Intelligence Quotient (IQ) values were higher among children in intervention Anganwadi centers (16.2 points for DQ and 10.2 points for IQ). This difference was found statistically significant (p = <0.01). Mean DQ among boys was found 10.1 points higher than that among the girls in control arm, this was statistically significant. According to multivariate linear regression model, the determinants of DQ were: intervention; age of the child; education of mother; sex of child; and PEM grade and the determinants for IQ were: intervention; age of the child; and income. CONCLUSION: This study shows that intervention to improve the Early Childhood Education and Development component through Anganwadi centers results in improvement in Developmental and Intelligence Quotient of children. PMID- 20358313 TI - Unusual presentations of malaria in children: an experience from a tertiary care center in North East India. AB - OBJECTIVE: To identify cases of malaria with unusual presentations. METHODS: The medical record of all the cases of malaria admitted to PICU and pediatric general ward from Oct 2006 to Sep 2009, were reviewed and cases with unusual presentations were identified. The study design was retrospective descriptive study. RESULTS: Sixteen (10%) out of 162 malaria cases had unusual presentations three had hemiplegia, two each with viral hepatitis-like presentation, acute abdomen, gastrointestinal bleed, generalized edema and hyperglycemia and one each with ptosis, severe headache and subacute intestinal obstruction-like presentation. Eleven cases had mixed parasitemia and two each with P. vivax and P. falciparum. One case was diagnosed on clinical grounds. CONCLUSION: Malaria is a common disease, but both typical and atypical presentations deserve attention for early diagnosis and management. PMID- 20358314 TI - The relationship between the waist-to-height ratio and glucose and lipid metabolism in Han adolescents. AB - OBJECTIVE: To evaluate the relationship between waist-to-height ratio (WHtR) and glucose and lipid metabolism in Han adolescents aged 13-15 years. METHODS: A study was conducted on 1665 Han adolescents aged 13-15 years. Measurements included height, weight, waist circumference, fasting plasma glucose(FPG), triglyceride and high-density lipoprotein cholesterol. The subjects were divided into two groups according to WHtR. RESULTS: Compared with the control group (n=1340,WHtR<0.46), the abdominal obesity group(n=325,WHtRe"0.46) had significantly higher levels of body mass index (BMI) (26.3+/-3.6 vs 18.9+/-2.3), WHtR (0.51+/-0.04 vs 0.40+/-0.03), FPG (4.99+/-0.48 vs 4.86+/-0.46), and triglyceride (1.21+/-0.62 vs 0.87+/-0.41), and a lower level of high-density lipoprotein cholesterol (1.26+/-0.27 vs 1.46+/-0.30) (P<0.01). Logistic regression analysis showed that after controlling for age, sex and BMI, the elevated FPG and dyslipidemia risk odds ratios of the abdominal obesity group were 1.954 (95% CI:1.250 approximately 3.054) and 2.012 (95% CI:1.204 approximately 3.362) (P<0.01) respectively. When clustered, the odds ratio of elevated FPG and dyslipidemia was 6.659 (95% CI: 1.337 approximately 33.159) (P<0.01). CONCLUSION: The waist-to-height ratio is an appropriate measure to assess dyslipidemic-diabetic adolescents and should be used to guide early intervention with the aim of future prevention of these linked diseases. PMID- 20358315 TI - Management of pain in leukemic children using the WHO analgesic ladder. AB - OBJECTIVE: To ascertain the effectiveness of WHO analgesic ladder in pain management in children with leukemia. METHODS: Children with leukemia who were referred to a pain and palliative care clinic attached to the Department of Pediatrics of a medical teaching hospital during a period of 6 months were included in the study. RESULTS: Thirty nine (39) children, who constituted 64% of children on treatment for leukemia, required referral to pain and palliative care services during the study period. Of these 92% had Acute Lymphocytic Leukemia (ALL) and 8% had Acute Non Lymphocytic Leukemia (ANLL). 95% of children had nociceptive pain and 5% had neuropathic pain. Step - 1 analgesia was effective in 12 (31%) children and 21 (54%) could be managed with Step - 2 analgesia. Step - 3 analgesia was required in only 6 (15%) children. Step 3 analgesia was required in children with neuropathic pain and bone pain. CONCLUSION: WHO analgesic ladder is effective in managing pain in children with leukemia. Majority of cases of cancer pain in children could be managed by the treating physician using non-opioids, weak opioids and adjuvants as per the WHO guidelines. Children with bone pain and neuropathic pain may require referral to specialist services and use of strong opioids like morphine. The study emphasizes the need for establishing specialist pain management services in all centres where children with cancer are treated. PMID- 20358316 TI - Treatment options for surgically resectable gastric cancer. AB - Surgery is the only curative therapy for gastric cancer. The standard recommendations for resectable gastric adenocarcinoma are free-margin surgery with at least D1 resection and the removal of a minimum of 15 lymph nodes. The overall 5-year survival rate for resected gastric patients remains poor due to locoregional recurrence. The results of a large North American study (Gastrointestinal Cancer Intergroup Trial INT 0116) reported that postoperative chemoradiotherapy conferred a survival advantage compared with surgery alone, which led to the regimen being adopted as a standard of care. More recently the MAGIC/UK Medical Research Council (MRC) trial demonstrated that perioperative chemotherapy resulted in an improvement in overall survival and progression free survival. Thus, two successful strategies are available to improve outcomes in patients with localized gastric cancer. This article reviews data on adjuvant and perioperative treatment modalities for gastric cancer. The article discusses ongoing randomized adjuvant and perioperative trials that are designed to optimize chemotherapy regimens and also investigate combinations of chemotherapy and biologic agents. It is important to understand the mechanisms or pathways involved in gastric cancer development and metastasis. Identification of novel molecules pivotal to tumor biology may lead to new therapeutic approaches for this malignancy. PMID- 20358318 TI - Anger suppression predicts pain, emotional, and cardiovascular responses to the cold pressor. AB - BACKGROUND: Manipulated anger suppression has been shown to heighten pain and anger responses to pain. PURPOSE: We examined whether individual differences in self-reported anger suppression predicted pain, anger, and blood pressure responses to acute pain. METHODS: Healthy participants (N = 47) underwent an anger-provoking speech task followed by a cold pressor pain task. Participants reported their degree of suppression of thoughts and feelings related to the speech. Pain intensity ratings were obtained throughout the cold pressor. Self reported anger, anxiety and positive emotion, as well as ratings of sensory, general distress, and anger-specific elements of pain were obtained following the cold pressor. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded throughout. RESULTS: Self-reported suppression predicted greater pain intensity ratings, perception of sensory and anger specific elements of pain, and self-reported anger in response to the cold pressor. Associations between self-reported suppression and pain intensity and ratings of anger-specific elements of pain were statistically mediated by pain induced changes in self-reported anger, whereas the effect of suppression on sensory pain ratings was not. Self-reported suppression was also correlated inversely with SBP responses to the cold pressor. CONCLUSIONS: Consistent with an ironic process model and prior studies involving experimental manipulation of suppression, self-reported suppression of anger predicted greater pain intensity and perception of the anger-specific element of pain. Findings also suggest that suppression might attenuate homeostatic pressor responses to acute pain. PMID- 20358319 TI - Is optimism associated with physical health? A commentary on Rasmussen et al. PMID- 20358320 TI - Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA). AB - Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is known about the peptides involved in the process. In this study, we investigated the possible involvement of HSPA in HLA class I or class II antigen presentation and analysed the antigenic potential of the associated peptides. HSPA was purified from CCRF-CEM and K562 cell lines, and using mass spectrometry techniques, we identified 44 different peptides which were co-purified with HSPA. The affinity of the identified peptides to two HSPA isoforms, HSPA1A and HSPA8, was confirmed using a peptide array. Four of the HSPA associated peptides were matched with 13 previously reported HLA epitopes. Of these 13 peptides, nine were HLA class I and four were HLA class II epitopes. These results demonstrate the association of HSPA with HLA class I and class II epitopes, therefore providing further evidence for the involvement of HSPA in the antigen presentation process. PMID- 20358321 TI - Psychometric properties of the processes of change scale for smoking cessation in UK adolescents. AB - BACKGROUND: The transtheoretical model (TTM) proposes that individuals move stage and hence change behaviour through the use of processes of change (POC)- cognitive, emotional and behavioural activities related to the target behaviour. PURPOSE: This study was a test of the psychometric properties of the POC scale. METHOD: The sample consisted of year 9 students from 26 schools who completed a computer-based version of the POC questionnaire on up to three occasions. There were 1,160 former and current smokers who completed the questionnaire on the first occasion, 978 on the second, and 836 on the third occasion. Confirmatory factor analysis was used to explore three alternative factor structures. Cronbach alpha and test-retest reliability coefficients were examined. Construct validity was examined by calculating POC means for each stage and testing differences between means using analysis of variance. RESULTS: The TTM-hypothesised second order factor that clustered ten primary factors into experiential and behavioural processes fitted the data reasonably, though an alternative model, removing the second-order factors, was a significantly improved fit. Cronbach alpha coefficients were reasonable except for two processes. Test-retest reliabilities were modest. Experiential processes showed differences across precontemplation to preparation, but differences between preparation, action, and maintenance were slight. Behavioural processes showed linear differences between stages, though helping relationships was not different across stages. CONCLUSIONS: There is evidence of some specific difficulties with the POC questionnaire that may be overcome with some reformulation. The POC questionnaire shows evidence of adequate factorial validity, sufficient to allow its use in future predictive testing. PMID- 20358322 TI - [Abstracts of the 116th Internal Medicine Congress. April 10-14, 2010, Wiesbaden, Germany]. PMID- 20358323 TI - [Orthotic methods for osteoporosis and osteoporotic vertebral fracture]. AB - Even in times of kyphoplasty and vertebroplasty, braces remain an efficient option in the treatment of osteoporotic hyperkyphosis due to imminent or manifest vertebral wedging with the obligatory pain and fracture risk of adjacent vertebraes. In the same fashion, acute osteoporotic fractures with considerable backpain can be treated with an adequate orthosis besides analgetics and osteological drugs. Essential is the careful selection of the right brace for a given type of osteoporotic fracture: Overall brace-frames (Stagnara type) should be used only in highly unstable or multiple osteoporotic fractures with impact onto the spinal canal where surgery is not possible. These brace frames should be administered only for the shortest possible period (8-12 weeks) to reduce muscle atrophy and immobilization. However, in the typical stable osteoporotic wedge fracture, light weight constructions like the Jewett or Bahler-Vogt brace or - in less severe cases - dynamic braces (e.g. TorsoStretch brace or SpinoMedActive brace) should be used to minimize muscle atrophy and demineralisation. Brace treatment at its best though, can be only one step in the cascade of measures to fight demineralisation and the clinical consequences: General physiotherapy, analgetics and specific osteological drugs and minerals add essentially to the treatment. PMID- 20358324 TI - [Stabilization of the osteoporotic spine from a biomechanical viewpoint]. AB - The altered trabecular structure of the osteoporotic spine leads to an increased vulnerability of its biomechanical characteristics and reduction of load resistance. Therefore, any surgical procedure must account for these circumstances. In cement-augmented vertebrae, both the overall stability and load transfer to the adjacent structures are influenced by a variety of factors. This has been demonstrated by different findings regarding volume, special characteristics, choice of approach and application, as well as distribution of the cement within the vertebral body. Independent of the well-known good clinical results, these features leave the discussion regarding the most appropriate form of cement-augmenting technique open. In cases where implants are required, there are increasing data to allow for an appropriate choice of stabilizing devices to fit the biomechanical demands in poor bone quality. Thereby, multilevel instrumentation, additive stabilization techniques, cement-augmented pedicle screws and adapted implant designs ensure and increase patient safety. However, regardless of the procedure chosen to stabilize the osteoporotic spine, reconstruction of the column profile appears to be of pre-eminent importance. PMID- 20358325 TI - [Instrumental fixation in spinal surgery. Particular characteristics in patients with manifest osteoporosis]. AB - A number of factors need to be borne in mind in the planning and performance of instrumental fixation of the spine in patients with osteoporosis. Improved implant anchoring using special screws and cement augmentation can help to avoid implant dislocations. Nevertheless, particular attention should be paid to spinal balance in these patients. PMID- 20358326 TI - Envisioning the evolution of orthopedic surgery in the twenty-first century. PMID- 20358327 TI - Statistics for orthopedic surgery 2006-2007: data from the Japanese Diagnosis Procedure Combination database. AB - BACKGROUND: The epidemiology of orthopedic surgery cases in Japan has not been determined adequately. This study analyzed statistics in orthopedic surgery for 2006 and 2007 using the Japanese Diagnosis Procedure Combination database. METHODS: Data were collected between July 1 and December 31 in both 2006 and 2007. We selected 78 diagnostic groups of musculoskeletal diseases and trauma, and recategorized them into eight specialties: trauma, spine, knee joint, hip joint, hand, oncology, rheumatoid arthritis, others. We then focused on the following five major diseases or procedures: spinal canal stenosis, disc degeneration or herniation, hip fracture, total hip arthroplasty, and total knee arthroplasty. We extracted the following information: type of admission, use of ambulance, age, sex, preoperative co-morbidities, surgical procedures, postoperative complications such as surgical-site infection or pulmonary embolism, in-hospital mortality, length of stay, and costs. RESULTS: A total of 226 644 patients were included. Approximately 33% were emergency cases. More than half of the patients were >or=60 years old. The surgery rate increased with age, with 13.1% of cases in their fifties to 22% in their seventies. The highest rate of surgery of the spine (5.8%), knee joint (4.5%), or hip joint (1.8%) occurred in patients in their seventies, and the highest rate of surgery for trauma (9.1%) occurred in patients in their eighties. The overall in-hospital mortality was 0.41%. Approximately 0.63% patients had a surgical-site infection, 0.22% had pulmonary embolism, 0.54% had cardiac events, and 0.41% had respiratory disorders. Hip fracture surgeries resulted in relatively high in-hospital mortality (1.38%) and postoperative complication rate (3.6%). CONCLUSIONS: This study presents an overview of the clinical features of orthopedic surgery in Japan, which may be of value for determining therapeutic strategies in the management of orthopedic surgery patients. PMID- 20358328 TI - Two-year results for scoliosis secondary to Duchenne muscular dystrophy fused to lumbar 5 with segmental pedicle screw instrumentation. AB - BACKGROUND: Instrumentation and fusion to the sacrum/pelvis has been a mainstay in the surgical treatment of scoliosis in patients with Duchenne muscular dystrophy since the development of the intrailiac post. It is recommended for correcting pelvic obliquity. However, caudal extent of instrumentation and fusion has remained a matter of considerable debate. This study was performed to determine the efficacy and safety of stopping segmental pedicle screw constructs at L5 during surgical treatment of scoliosis associated with Duchenne muscular dystrophy (DMD). METHODS: From May 2005 to June 2007, a total of 20 consecutive patients underwent posterior spinal fusion and segmental pedicle screw instrumentation only to L5 for scoliosis secondary to DMD. All patients had progressive scoliosis, difficulty sitting, and back pain before surgery. A minimum 2-year follow-up was required for inclusion in this study. Assessment was performed clinically and with radiological measurements. The Cobb angles of the curves and spinal pelvic obliquity were measured on the coronal plane. Thoracic kyphosis and lumbar lordosis were measured on the sagittal plane. These radiographic assessments were performed before surgery, immediately after surgery, and at a 3-month interval thereafter. The operating time, blood loss, and complications were evaluated. Patients were questioned about whether they had difficulty sitting and felt back pain before surgery and at 6 weeks, 1 year, and 2 years after surgery. RESULTS: A total of 20 patients, aged 11-17 years, were enrolled. The average follow-up period was 37 months. Preoperative coronal curves averaged 70 degrees (range 51 degrees -85 degrees ), with a postoperative mean of 15 degrees (range 8 degrees -25 degrees ) and a mean of 17 degrees (range 9 degrees -27 degrees ) at the last follow-up. Pelvic obliquity improved from 13 degrees (range 7 degrees -15 degrees ) preoperatively to 5 degrees degrees (range 3 degrees -8 degrees ) postoperatively and 6 degrees (range 3 degrees -9 degrees ) at the last follow-up. Good sagittal plane alignment was recreated and maintained. Only a small loss of correction of scoliosis and pelvic obliquity was noted. The mean operating time was 271 min (range 232-308 min). The mean intraoperative blood loss was 890 ml (range 660-1260 ml). The mean total blood loss was 2100 ml (range 1250-2880 ml). There was no major complication. All patients reported that difficulty sitting and back pain were alleviated after surgery. CONCLUSION: Segmental pedicle screw instrumentation and fusion only to L5 is safe and effective in patients with DMD scoliosis of <85 degrees and pelvic obliquity of <15 degrees . Good sagittal plane alignment was achieved and maintained. All patients benefited from surgery in terms of improved quality of life. There was no major complication. PMID- 20358329 TI - Early surgery-related complications after anteroposterior stabilization of vertebral body fractures in the thoracolumbar region. AB - BACKGROUND: The complication rate after trauma-associated spine surgery remains unknown because of the rarity of this injury and the polymorphism of treatment methods. We report the complication rates recorded at one center after treatment of unstable vertebral body fractures according to a single, uniform procedure. The aim of this analysis was to identify the typical complications associated with this surgical procedure and, consequently, to contribute to critical deliberations on the introduction of technical innovations such as navigation, intraoperative three-dimensional imaging, and neuromonitoring. METHODS: Perioperative complications related to surgery of 208 consecutive patients, operated on for unstable vertebral body fractures were analyzed. First, stabilization was performed through an open, posterior, nonnavigated approach. This was followed, in all patients, by reconstruction of the anterior column form with a tricortical iliac crest graft during a second operation. RESULTS: In regard to posterior stabilization, at least one pedicle screw in six patients (3%) was placed incorrectly; furthermore, there were five patients with general complications, all of which required revision surgery. After anterior spondylodesis, there were also nine general complications and five neurological complications, one of them in a patient with persistent paraplegia. At the graft donor site, three patients experienced an avulsion fracture of the anterosuperior iliac crest. Overall, at least one complication occurred in 13% of patients (confidence interval 0.08-0.18). CONCLUSIONS: With regard to early complications, two-stage anteroposterior stabilization of unstable spinal fractures of the thoracolumbar spine is a reliable procedure. PMID- 20358330 TI - Impact of oral corticosteroid use for idiopathic osteonecrosis of the femoral head: a nationwide multicenter case-control study in Japan. AB - BACKGROUND: Previous studies on corticosteroid use and idiopathic osteonecrosis of the femoral head (ONF) have been conducted involving patients with systemic lupus erythematosus and renal transplantation, among other disorders, which make it possible only to compare high- and low-dose corticosteroids. The main objective here was to estimate the impact of oral corticosteroid use for idiopathic ONF compared to nonuse of corticosteroids. In addition, we investigated the relations between underlying medical conditions and idiopathic ONF. METHODS: A nationwide multicenter case-control study was conducted in Japan. Cases were defined as patients who visited the cooperative orthopedic department after January 2002 and received a diagnosis of idiopathic ONF after the visit. For each case, up to five matched controls were selected from among patients without idiopathic ONF who consulted the same orthopedic department after the visit of the identified case. The matching conditions were sex, age (5-year age groups), and ethnicity. The subjects' demographic and anthropometric data and histories of medications, diseases, alcohol consumption, and smoking were collected by a structured self-administered questionnaire. A conditional logistic regression model was used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 73 cases and 250 matched controls completed the questionnaire. After adjustment for the potential confounders, the multivariate OR of oral corticosteroid use compared to nonuse was 20.3 (95% CI 6.73-61.5). Furthermore, a positive association of liver disease with idiopathic ONF was observed with marginal significance (multivariate OR 3.53, 95% CI 0.88 14.1) regardless of oral corticosteroid use, alcohol consumption, and smoking. CONCLUSIONS: The current findings first revealed the impact of oral corticosteroid use for idiopathic ONF compared to nonuse. However, because the regimen of corticosteroid therapy (dose and duration) could not be assessed, further study is required. An independent role of liver disease was also suggested. PMID- 20358331 TI - Risk factors for second hip fractures among elderly patients. AB - BACKGROUND: Hip fractures following falls by the elderly, which increase with age, are increasing in number annually. The incidence of refracture (second hip fractures) has been reported to be 5%-10% in Japan and is expected to increase with the aging of the population in the future. Therefore, through a retrospective cohort study, we attempted to clarify the risk factors associated with second hip fractures. METHODS: A total of 400 patients were consecutively treated for hip fracture at a single orthopedic hospital between January 2001 and December 2007. We excluded 16 subjects: 11 patients who died within a year after a hip fracture and 5 who were <50 years of age. The remaining 384 patients, consisting of 64 men and 320 women, were chosen as the study subjects. The mean age of the subjects at the time of the initial fracture was 83.1 +/- 9.0 years (range 51-102 years). Age, sex, interval between the two fractures, body mass index (BMI), length of bed-rest periods and of rehabilitation periods, living place after an initial fracture, and complicating diseases were determined from medical records. Furthermore, effectors of second hip fractures were extracted using the Cox proportional hazard model. RESULTS: In all, 384 patients were observed for 1140.0 person-years (mean: 3.0 +/- 1.4 years per patient) following the initial hip fracture. During the observation period, 49 second hip fractures were identified, giving an overall incidence of 0.043 per person-year. The second fracture occurred within 3 years in 85.7% (42 patients). Dementia and respiratory disease were recognized as being significantly related to refracture. Using a Cox proportional hazard model, dementia showed a significant influence, with the hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.02-3.41; P = 0.042]. Respiratory diseases also were associated with second hip fracture (HR 4.41, 95% CI 2.33-8.34; P < 0.001). CONCLUSIONS: In this study, 85.7% of refractures occurred within 3 years of the first fracture, with dementia and respiratory disease being the complicating factors that influenced refracture. PMID- 20358332 TI - Clinical and radiological outcomes of postoperative septic arthritis after anterior cruciate ligament reconstruction. AB - BACKGROUND: Septic arthritis after arthroscopic anterior cruciate ligament (ACL) reconstruction is a rare complication. In the literature, several treatments have been proposed. The aim of the study was to report our results using ambulatory irrigation of the knee and parenteral and oral antibiotics. METHODS: From January 2001 to December 2008, a total of 12 patients were treated for postoperative septic arthritis of the knee after ACL reconstruction in our hospital. The average age at trauma was 24 years (range 16-43 years). The treatment protocol included irrigation of the knee (for 2 days) and parenteral antibiotics and oral antibiotics subsequently. Repetitive irrigation was performed if necessary. The average duration of follow-up for our series was 38 months (range 6-54 months). Follow-up included International Knee Documentation Committee (IKDC) forms, radiography, Tegner and Lysholm scores, and KT-1000 arthrometric evaluation. RESULTS: In all cases treatment of infection was successful. Neither graft nor hardware removal was needed in any of the cases. At final examination, the pivot shift was negative in 10 of 12 patients, and it was 1+ in the other 2 patients; the Lachman was negative in all cases. The mean postoperative Tegner score was 7.2, and the mean Lysholm score was 98.3. In all, 10 of the 12 patients were graded as group A and the other 2 as group B using the IKDC form. The mean postoperative manual maximum KT-1000 side-to-side difference was 2.3. No significant bone tunnel enlargement was found at radiographic evaluation. CONCLUSIONS: The described treatment regimen gives reliable results for this complication. There were no recurrences of septic arthritis or bone infection. No further surgeries were required, and the graft was retained during the treatment of septic arthritis. PMID- 20358333 TI - Clinical and radiological results of calcium phosphate cement-assisted balloon osteoplasty for Colles' fractures in osteoporotic senile female patients. AB - BACKGROUND: Distal radius fractures in osteoporotic senile female patients often used to be complicated with residual deformity, stiffness, and pain. Recently, however, adequate usage of a palmar locking plate or external fixation has led to fewer subsequent complications. The method proposed here deserves consideration because it is less invasive and more cost-effective. METHODS: A total of 11 Colles' type fractures (AO type A2) in 11 patients (all female; mean age 78 years) were treated. After a closed reduction, the fractures were fixed by percutaneous pinning, as Kapandji previously described. Through a 5-mm longitudinal skin incision on the dorsoulnar aspect of the fracture site, the barrel of a disposable 1-ml syringe was inserted into the fracture site as a port. Next, a pediatric uromatic balloon was introduced into the fracture site and inflated by contrast medium. The balloon inflation enlarged the void of the fracture site. A compression bandage around the fracture site was applied before calcium phosphate cement injection with a cement gun through the port under an image intensifier. The functional and radiological results were evaluated. The mean follow-up period was 16 months (range 12-25 months). RESULTS: All results were graded as good or excellent within 3 months, and all were graded as excellent at the final follow-up. The average duration of immobilization was 4 weeks with a short forearm cast. The overall postoperative correction loss in ulnar variance was 1.7 mm. Radial inclination and volar tilt showed no postoperative correction loss. The final volar tilt, radial inclination, and ulnar variance were comparable to those of the nonaffected side. CONCLUSIONS: Calcium phosphate cement-assisted balloon osteoplasty is a less invasive procedure and can be clinically justified as a therapeutic option for a Colles' fracture in osteoporotic senile female patients. PMID- 20358334 TI - Importance of distal radioulnar joint arthroscopy for evaluating the triangular fibrocartilage complex. AB - BACKGROUND: The present study evaluated the importance of visualizing both sides of the triangular fibrocartilage complex (TFCC) when diagnosing ulnar wrist pain. METHODS: A total of 20 patients with ulnar wrist pain who underwent both radiocarpal joint (RCJ) and distal radioulnar joint (DRUJ) arthroscopy were studied retrospectively. TFCC was graded as normal or as having wear or tear. The definitive diagnosis was made by evaluating the TFCC from both joints. The medical records were reviewed to document the preoperative diagnosis, arthroscopic findings, postoperative diagnosis, and operative procedure(s) performed after the arthroscopic examinations. The patients' status at final follow-up was evaluated using the modified Green and O'Brien wrist scoring system. The TFCC grading on RCJ and DRUJ arthroscopies was compared. RESULTS: The final diagnosis was modified after arthroscopic examination in three cases (15%). In six patients (30%), DRUJ arthroscopy revealed pathological TFCC findings that could not be detected on RCJ arthroscopy. The DRUJ arthroscopy detected wear or degenerative changes seen only on the proximal aspect of the TFCC in four patients and tear in two patients. On the other hand, in only one patient (5%) were there no pathological findings observed from the DRUJ portal, although RCJ arthroscopy found wear. In eight patients (45%), the arthroscopic grading of TFCC was the same on RCJ and DRUJ arthroscopy; of these, the TFCC was graded as normal in one patient, showing wear in three patients, and with a tear in five patients. For diagnosing TFCC pathology, RCJ arthroscopy had a sensitivity of 68% and a negative predictive value (NPV) of 14%, whereas the sensitivity was 95% and the NPV was 50% for DRUJ. CONCLUSIONS: Adding DRUJ arthroscopy to RCJ arthroscopy enables more accurate diagnosis of TFCC pathology because the proximal aspect of the articular disk and the foveal insertion of the distal radioulnar ligament can be visualized. PMID- 20358335 TI - Does an ulnar styloid fracture interfere with the results of a distal radius fracture? AB - BACKGROUND: The ulnar styloid is a supportive structure for the capsular ligament complex of the distal radioulnar joint. The relation between fractures of the ulna and distal radius is not clear, especially in regard to whether ulnar fractures predict worse outcomes for distal radius fractures. The objective of this study was to analyze the influence of ulnar styloid fractures in patients with reducible and unstable distal radius fractures. METHODS: A total of 100 patients with unstable and reducible distal radius fractures, with or without an ulnar styloid fracture, were randomly assigned to treatment with transarticular bridging external fixation or transulnar percutaneous pinning. Follow-up was obtained for 91 patients. For the secondary data analysis, three patient cohorts were created: a no ulnar styloid fracture group with the radius fracture treated by pinning or external fixation (n = 30); an ulnar styloid fracture with radius fracture group treated by external fixation (n = 31); and an ulnar styloid fracture with radius fracture treated by pinning (n = 30). Functional and radiological outcomes were measured at 6 and 24 months. Functional outcome measures included wrist pain (visual analogue scale) and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: At 24 months, patients with both fractures had worse wrist pain and worse scores on the DASH questionnaire than the patients with an isolated distal radius fracture; and those treated by pinning had less wrist pain and showed better scores on the DASH questionnaire than the patients treated by fixation. CONCLUSIONS: Ulnar styloid fracture may be a predictive factor of worse functional outcome for distal radius fracture. Pinning and above-the-elbow casting, used to treat ulnar styloid fractures, led to better function than fixation. PMID- 20358336 TI - Clinical result of sintered bovine hydroxyapatite bone substitute: analysis of the interface reaction between tissue and bone substitute. AB - BACKGROUND: Autogenic bone graft is the first choice for managing bone defects. However, donor site-associated morbidity and limited bone volume are constraints in clinical applications. Allografts can provide sufficient amounts for bone defects but have a high risk of infection. Bone substitute composed of hydroxyapatite (HA) is an alternative material for avoiding the aforementioned risks. Sintered bovine bone is a naturally occurring HA that has been proved to have excellent bioactivity for inducing osteoblastic expression and new bone formation in animal studies. The objective of this study was to evaluate the interactions between the tissue and the bone substitute composed of HA (sintered from bovine bone) in the human body. METHODS: From 2003 to 2005, a total of 33 patients were enrolled to receive the sintered bovine HA as a bone substitute. Inclusion criteria were fractures with bony defects, benign bone tumors with a cavity, and spinal fusions. Bone healing was monitored by a series of radiographs, and bone microstructure was checked by scanning electron microscopy (SEM) and von Kossa staining. RESULTS: In 81.8% (27/33) of cases, significant fusion mass formation was visible in the radiographs after 6-12 months. New bone formation on the surface of the sintered bovine HA was seen under microscopic observation. Tight bonding between the interface of the bone and the sintered bovine HA was shown with SEM/energy-dispersive spectroscopy and von Kossa staining. CONCLUSIONS: Sintered bovine HA is a suitable material as a bone substitute to provide bone growth and promote bone healing. PMID- 20358337 TI - Effect of near-infrared light-emitting diodes on nerve regeneration. AB - BACKGROUND: Photobiomodulation by red to near-infrared light-emitting diodes (LEDs) has been reported to accelerate wound healing, attenuate degeneration of an injured optic nerve, and promote tissue growth. The purpose of this study was to investigate the effect of LEDs on nerve regeneration. A histological study as well as a measurement of antioxidation levels in the nerve regeneration chamber fluid was performed. METHODS: For the histological study, the bilateral sciatic nerves were transected, and the left proximal stump and the right distal stump were inserted into the opposite ends of a silicone chamber, leaving a 10-mm gap. Light from an LED device (660 nm, 7.5 mW/cm(2)) was irradiated for 1 h per day. At 3 weeks after surgery, regenerated tissue was fixed and examined by light microscopy. For the antioxidation assay of chamber fluid, the left sciatic nerve and a 2-mm piece of nerve from the proximal stump were transected and inserted into opposite sides of a silicone chamber leaving a 10-mm gap. LEDs were irradiated using the same parameters as those described in the histological study. At 1, 3, and 7 days after surgery, antioxidation of the chamber fluid was measured using an OXY absorbent test. RESULTS: Nerve regeneration was promoted in the LED group. Antioxidation of the chamber fluid significantly decreased from 3 days to 7 days in the control group. In the LED group, antioxidation levels did not decrease until 7 days. CONCLUSIONS: Chamber fluid is produced from nerve stumps after nerve injury. This fluid contains neurotrophic factors that may accelerate axonal growth. Red to near-infrared LEDs have been shown to promote mitochondrial oxidative metabolism. In this study, LED irradiation improved nerve regeneration and increased antioxidation levels in the chamber fluid. Therefore, we propose that antioxidation induced by LEDs may be conducive to nerve regeneration. PMID- 20358338 TI - Effect of low-intensity pulsed ultrasound on fracture callus mineral density and flexural strength in rabbit tibial fresh fracture. AB - BACKGROUND: Low-intensity ultrasound is a biophysical intervention on a fracture repair process. However, the effect of low-intensity ultrasound therapy on fracture healing is controversial. The aim of the present study was to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) therapy on the fracture healing process, including mineral density and strength of callus using a rabbit model. METHODS: A total of 30 rabbits underwent unilateral, transverse, and mid tibia open osteotomies that were stabilized with external fixators. Then, the animals were divided into two study groups composed of 15 rabbits each: the case group (US), which were exposed to low-intensity pulsed ultrasound with 30 mW/cm(2) intensity and 1.5 MHz sine waves; and the control group (C), which underwent sham ultrasound treatment. Callus development and mineral density were evaluated using multidetector computed tomography at 2, 5, and 8 weeks, after which the animals were killed. Three-point bending tests of both healed and intact bones were assessed and compared. RESULTS: The results demonstrated that the callus mineral density in the US group was higher than in the C group (1202.20 +/- 81.30 vs. 940.66 +/- 151.58 HU; P = 0.001) at the end of the 8th week. The mean recorded three-point bending test score of healed bones in the US group was not significantly different from that of the C group (359.35 +/- 173.39 vs. 311.02 +/- 80.58 N; P = 0.114). CONCLUSIONS: The present study showed that low-intensity pulsed ultrasound enhanced callus mineral density with an insignificant increase in the strength of the fractured bone. PMID- 20358339 TI - Optimum predrilled hole size for bone screws used in osteochondral fixation: in vitro biomechanical study and clinical case. AB - BACKGROUND: Bone screws have a mechanical advantage over bone pegs for fixation of osteochondral fractures. The purpose of this study was to investigate predrilling methods to facilitate bone screw insertion. METHODS: The 162 bone screws (major diameter 3.0 mm; minor diameter 2.5 mm; length 10 mm) used were made from porcine tibial cortical bone. Metal screws of the same design were used as a control. The screws were inserted, without tapping, into predrilled holes of six different sizes (2.4-2.9 mm diameter; 80%-97% of the screw) made in cancellous bone harvested from porcine femoral condyle, and pullout strength was determined. The volumetric bone mineral densities of porcine bones were compared to those of human bones. In a clinical case, an osteochondral fracture of the patella was repaired using three autologous bone screws. RESULTS: Bone screws occasionally broke due to high insertion torque (108-158 N.mm); the incidences were 30% and 19% with the 80% and 83% sized holes, respectively. None of the screws inserted into holes of size >/= 87% broke, and their insertion torques never exceeded 100 N.mm. Metal screws were inserted without breakage regardless of hole size. Bone screws inserted into 80%-93% holes had the greatest pullout strengths (range 154-165 N), whereas 97% holes had a mean strength of 84 N. Metal screws had large pullout strengths when inserted into 80% and 83% holes (164 and 169 N, respectively). The mineral density of porcine bone was lower than that of human bone (1167 and 1357 mg/cm(3) for cortical bone and 193 and 269 mg/cm(3) for cancellous bone, respectively). In the clinical case, bone screws were inserted smoothly into 90% holes. CONCLUSIONS: The optimal size of predrilled holes for bone screws (87%-93%) differs from that for metal screws. PMID- 20358340 TI - Mucoid degeneration of the anterior cruciate ligament associated with subclinical instability in young patients. PMID- 20358341 TI - Unreduced atlantoaxial dislocation locked with a combined lateral mass fracture. PMID- 20358342 TI - Ganglion cyst arising from the posterolateral capsule of the knee. PMID- 20358343 TI - Osteosarcoma with metastasis to the stomach. PMID- 20358344 TI - Anatomic double-bundle anterior cruciate ligament reconstruction. PMID- 20358345 TI - Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat. AB - 11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HCl stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old maleSprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus. PMID- 20358346 TI - Protective effects of caffeic acid phenethyl ester on iron-induced liver damage in rats. AB - Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti inflammatory, antitumor, and antioxidant activities, and attenuates inflammation and lipid peroxidation. The purpose of the present study was to investigate the effects of CAPE on iron-induced liver damage. Rats were divided into four groups and treated for 7 days with saline (control group), 10 micromol kg CAPE/day s.c. (CAPE group), 50 mg iron-dextran/kg i.p. (IRON group) and CAPE and iron at the same time (IRON+CAPE group). Seven days later, rats were killed and the livers were excised for biochemical analysis. The administration of IRON alone resulted in higher myeloperoxidase (MPO) activity and lipid peroxidation than in the control and CAPE treatment prevented the increase in MPO activity and malondialdeyde (MDA) level. No differences were observed in all four groups with regards to superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Our results collectively suggest that CAPE may be an available agent to protect the liver from injury via inhibition of MPO activity. PMID- 20358347 TI - Altered food consumption in mice lacking lysophosphatidic acid receptor-1. AB - The release of lysophosphatidic acid (LPA) by adipocytes has previously been proposed to play a role in obesity and associated pathologies such as insulin resistance and diabetes. In the present work, the sensitivity to diet-induced obesity was studied in mice lacking one of the LPA receptor subtype (LPA1R). Conversely to what was observed in wild type (WT) mice, LPA1R-KO-mice fed a high fat diet (HFD) showed no significant increase in body weight or fat mass when compared to low fat diet (LFD). In addition, in contrast to what was observed in WT mice, LPA1R-KO mice did not exhibit over-consumption of food associated with HFD. Surprisingly, when fed a LFD, LPA1R-KO mice exhibited significant higher plasma leptin concentration and higher level of adipocyte leptin mRNA than WT mice. In conclusion, LPA1R-KO mice were found to be resistant to diet-induced obesity consecutive to a resistance to fat-induced over-consumption of food that may result at least in part from alterations in leptin expression and production. PMID- 20358348 TI - Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes. AB - Visfatin, a protein identified as a secretion product of visceral fat in humans and mice, is also expressed in different anatomical locations, and is known as pre-B cell-colony enhancing factor (PEBF1). It is also an enzyme displaying nicotinamide phosphoribosyltransferase activity (Nampt). The evidence that levels of visfatin correlate with visceral fat mass has been largely debated and widely extended to other regulations in numerous clinical studies and in diverse animal models. On the opposite, the initial findings regarding the capacity of visfatin/Nampt/PEBF1 to bind and to activate the insulin receptor have been scarcely reproduced, and even were contradicted in recent reports. Since the putative insulin mimicking effects of visfatin/Nampt/PEBF1 have never been tested on mature human adipocytes, at least to our knowledge, we tested different human visfatin batches on human fat cells freshly isolated from subcutaneous abdominal fat and exhibiting high insulin responsiveness. Up to 10 nM, visfatin was devoid of clear activatory action on glucose transport in human fat cells while, in the same conditions, insulin increased by more than threefold the basal 2 deoxyglucose uptake. Moreover, visfatin was unable to mimic the lipolysis inhibition induced by insulin. Visfatin definitively cannot be considered as a direct activator of insulin signalling in human fat cells. Nevertheless itsin vivo effects on insulin release and on glucose handling deserve to further study the role of this multifunctional extracellular enzyme in obese and diabetic states. PMID- 20358349 TI - Native fructose extracted from apple improves glucose tolerance in mice. AB - Fructose is one of the most abundant monosaccharide in nature. It is also the sweetest naturally occurring carbohydrate. Since decades, fructose used for food preparations is not provided by fruit or vegetable but by a chemical process of starch or inulin conversion. We processed a new method of fructose extraction from apple and investigated the acute and long term effect of this carbohydrate on glucose metabolism in C57Bl6/j mice. By using the glycemic index (GI), we have shown that one of the sugars obtained from apple, FructiLight, has a very low impact on glycemic and insulin response during acute treatment compared to other sugars. This carbohydrate, essentially constituted by fructose, has also beneficial properties when administrated for long term treatment. Indeed, as two other sugars extracted from apple (FructiSweetApple and FructiSweet67), FructiLight exposure during 21 weeks in beverage has promoted an enhancement of glucose tolerance compared to glucose treatment without affecting food intake and weight. All these results indicate that apple-extracted sugars and more precisely fructose from these fruits could be a promising way to produce new food and sweet beverages. PMID- 20358350 TI - Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet. AB - Recently resveratrol, a compound naturally occurring in various plants, has been proposed as a potential anti-obesity compound. The aim of the present work was to analyse the effects of different doses of resveratrol on body fat and serum parameters in rats. Thirty-two male Sprague-Dawley rats were randomly divided into four groups and fed on a hypercaloric diet for 6 weeks. The doses oftrans resveratrol used were 6, 30 and 60 mg/kg body weight/d in RSV1, RSV2 and RSV3 groups respectively. The stability of resveratrol when added to the diet was evaluated. Blood samples were collected, and white adipose tissue from different anatomical locations, interscapular brown adipose tissue, gastrocnemious muscles and liver were weighed. Commercial kits were used to measure serum cholesterol, glucose, triacylglycerols and non-esterified fatty acids. While the lowest dose did not have a body fat reducing effect, the intermediate dose reduced all the white adipose depots. The highest dose significantly reduced mesenteric and subcutaneous depots but not epididymal and perirenal tissues. Although the reduction in all the anatomical locations analysed was 19% in the RSV3 group, in the RSV2 group it was 24%. No significant differences among the experimental groups were found in brown adipose tissue, gastrocnemious muscle or liver weights. Serum parameters were not affected by resveratrol intake because no differences among the experimental groups were observed. These results suggest that resveratrol is a molecule with potential anti-obesity effect. The most effective of the three experimental doses was 30 mg/kg body weight/d. PMID- 20358351 TI - Possible mechanisms of weight loss of Siberian hamsters (Phodopus sungorus sungorus) exposed to short photoperiod. AB - Several weeks of short day photoperiod (SD) exposure promote a dramatic decrease of white adipose tissue (WAT) mass in Siberian hamsters(Phodopus sungorus sungorus). This slimming effect is accompanied by changes in the adipocyte responsiveness to adrenergic stimulation that are still under debate. We investigated whether possible changes in the antilipolytic responses, and/or lipogenic activities could be involved in such lipid deposition/mobilisation imbalance. Male Siberian hamsters were exposed for 11 weeks to SD or long day photoperiod and basal or stimulated lipolytic and lipogenic activities were measured on white adipocytes. As expected, the body mass of SD-animals was decreased. Besides a slight reduction in the basal lipolysis and in the maximal response to dibutyryl-cAMP, the responses to adrenergic and non-adrenergic lipolytic agents (forskolin, adenosine deaminase) were similar in both groups. Fat mass loss was likely not resulting from changes in the lipolytic responses of adipocytes to biogenic amines (e.g. octopamine), which were unaltered, or to a direct lipolytic stimulation by melatonin or histamine, which were inactive. Antilipolytic responses to insulin or tyramine were slightly decreased in SD adipocytes. Basal or insulin-stimulated lipid accumulation in WAT, measured by glucose incorporation into lipids, did not change after SD-exposure. However, a significant decrease in the lipoprotein lipase activity was observed in the WAT of SDanimals. Despite the observed changes, the weight loss of SD-exposed Siberian hamsters was likely not resulting only from impaired antilipolytic orde novo lipogenic activities in white adipocytes, but either from other dramatic changes occurring during seasonal photoperiod-sensitive body weight regulation. PMID- 20358352 TI - Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats. AB - The aim of this study was to investigate the role of dietary macronutrient content on adiposity parameters and adipocyte hypertrophy/hyperplasia in subcutaneous and visceral fat depots from Wistar rats using combined histological and computational approaches. For this purpose, male Wistar rats were distributed into 4 groups and were assigned to different nutritional interventions: Control group (chow diet); high-fat group, HF (60% E from fat); high-fat-sucrose group, HFS (45% E from fat and 17% from sucrose); and high-sucrose group, HS (42% E from sucrose). At day 35, rats were sacrificed, blood was collected, tissues were weighed and fragments of different fat depots were kept for histological analyses with the new softwareAdiposoft. Rats fed with HF, HFS and HS diets increased significantly body weight and total body fat against Control rats, being metabolic impairments more pronounced on HS rats than in the other groups. Cellularity analyses usingAdiposoft revealed that retroperitoneal adipose tissue is histologically different than mesenteric and subcutaneous ones, in relation to bigger adipocytes. The subcutaneous fat pad was the most sensitive to the diet, presenting adipocyte hypertrophy induced by HF diet and adipocyte hyperplasia induced by HS diet. The mesenteric fat pad had a similar but attenuated response in comparison to the subcutaneous adipose tissue, while retroperitoneal fat pad only presented adipocyte hyperplasia induced by the HS diet intake after 35 days of intervention. These findings provide new insights into the role of macronutrients in the development of hyperplastic obesity, which is characterized by the severity of the clinical features. Finally, a new tool for analyzing histological adipose samples is presented. PMID- 20358353 TI - A moderate intake of phytosterols from habitual diet affects cholesterol metabolism. AB - Cholesterol metabolism homeostasis is the result of a balance between synthesis, degradation and intestinal absorption. It is well established that intestinal cholesterol absorption efficiency can be modified by the intake of phytosterol enriched food and, therefore, have a serum cholesterol-lowering effect. Recent epidemiological and clinical studies have shown that presence of phytosterols at normal diet levels could also be effective on lowering total and LDL serum cholesterol since they affect whole-body cholesterol metabolism even at those moderate doses. The aim of this study was to analyze the effect of the levels of the naturally-occurring phytosterols in the diet on cholesterol metabolism parameters. In order to do that a group of 99 healthy volunteers was studied for their dietary habits and surrogate markers of cholesterol synthesis and absorption. The mean daily dietary intake of phytosterols, measured by a food semiquantitative frequency questionnaire, was found to be 494 mg being beta sitosterol the major contributor to it. Subjects were classified into tertiles according to their total phytosterol intake and comparisons were done between subgroups. No statistical differences were observed for surrogate markers of intestinal cholesterol absorption, but a significant increase in the cholesterol synthesis surrogate marker lathosterol-to-cholesterol ratio associated to highest dietary phytosterol intake was observed. Regardless of this, only a non significant trend toward a less atherogenic lipid profile was observed in the upper tertile. In conclusion, the intake of moderate amounts of phytosterols naturally present in habitual diet may affect cholesterol metabolism and specially the rate of cholesterol synthesis as estimated by the surrogate marker lathosterol-to-cholesterol ratio in serum. PMID- 20358354 TI - Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors. AB - During the last decades, the prevalence of obesity has increased rapidly among young people. A polymorphism in the promoter region of the IL6 gene (-174G/C), has been previously reported to be involved in obesity and metabolic syndrome development. Therefore, the aim of the study was to examine whether the IL6 174G/C polymorphism influence the association of body fat with low-grade inflammatory markers and blood lipids and lipoproteins in Spanish adolescents. 504 Spanish adolescents participating in the AVENA study were genotyped for the 174G/C polymorphism of the IL6 gene. Anthropometric and body composition measurements were taken and blood samples were collected for plasma molecules determinations. No differences between genotypes were observed in anthropometric values, body composition measurements and plasma markers concentration. Physical activity level differ between genotypes with subjects carrying the C allele of the polymorphism being significantly (p<0.05) more active than GG subjects. The association between body fat mass and plasma glucose was influenced by the 174G/C polymorphism of the IL6 gene. Subjects carrying the C allele of the mutation seem to have higher values of lipoprotein (a) and C-reactive protein as their percentage of body fat mass increase. Our results suggest that this promoter polymorphism influences the association between adiposity and some plasma markers. PMID- 20358355 TI - Abdominal fat and metabolic risk in obese children and adolescents. AB - The aim of this study was to investigate fat distribution, mainly abdominal fat, and its relationship with metabolic risk variables in a group of 126 children and adolescents (60 males and 66 females) aged 5.0 to 14.9. According to IOTF criteria, 46 were classified as normal weight, 28 overweight and 52 obese. Weight, height, waist (WC) and hip circumferences were measured. The body mass index (BMI) was calculated. Total body fat, trunkal and abdominal fat were also assessed by dual energy x-ray absorptiometry (DXA). Glucose, insulin, HDL Cholesterol, triglycerides (TG), ferritine, homocystein and C-reactive protein (CRP) were measured. Obesity status was related with insulin concentrations, CRP, TG and HDL. Obese patients had higher abdominal fat and higher CRP values than overweight and normal subjects. All markers of central body adiposity were related with insulin and lipid metabolism; however, they were not related with homocystein or ferritin. A simple anthropometric measurement, like waist circumference, seems to be a good predictor of the majority of the obesity related metabolic risk variables. PMID- 20358356 TI - Adipose tissue lymphocytes: types and roles. AB - Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development. PMID- 20358357 TI - [Bipolar depression. Spectrum of clinical pictures and differentiation from unipolar depression]. AB - Patients with bipolar disorder often present initially with a major depressive episode. The correct diagnosis at the first presentation could help to find an effective medication regimen, to prevent antidepressant-induced rapid cycling and to reduce antidepressant-induced manic episodes, e.g. though combination therapy with a mood stabilizer. Consistent predictors for an underlying bipolar illness are an early age of onset, a highly recurrent illness course with more than five episodes, the presentation of atypical features, psychotic symptoms, the presence of psychiatric comorbidities like anxiety disorders, history of suicide attempts (especially at an early age), positive family anamnesis for bipolar disorder, and a rapid evolvement of the depressive episode. So far there are no pathognomonic markers for bipolar disorder. Therefore we propose to assess the risk of each patient for having bipolar disorder individually. Patients who are at a high risk should at least be informed and should be closely monitored for the development of manic episodes. PMID- 20358358 TI - Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury. AB - Osteoporosis after spinal cord injury is common. Reductions in bone density are rapid and fracture rates are higher after injury. Early treatment with 4 mg zoledronic acid significantly reduced bone loss at the hip compared to untreated individuals in the first year. Treatment appeared safe and well tolerated. INTRODUCTION: Bone mineral density (BMD) is lost rapidly following spinal cord injury (SCI), predominantly in the lower limbs. Bone turnover markers suggest an early increase in resorption. METHODS: A randomised, open-label study of 14 patients with acute SCI randomised to receive 4 mg IV zoledronic acid or standard treatment. BMD was measured by dual-X-ray absorptiometry at the lumbar spine and hip (femoral neck, total and trochanter) at baseline, 3, 6 and 12 months. Bone turnover markers (serum C-terminal telopeptide and Procollagen I N-terminal peptide and urinary N-terminal telopeptide/Cr ratio) were also measured. RESULTS: After 12 months, there was a significant difference in BMD between the groups at the total hip (12.4%, p = 0.005), trochanter (13.4%, p = 0.028) and lumbar spine (2.7%, p = 0.033). However, the difference between groups at the femoral neck was not significant (4.8%, p = 0.741). In the treated group, bone resorption was reduced and remained reduced up to 12 months. Other than flu-like symptoms immediately after the infusion, no adverse events were observed. CONCLUSION: IV zoledronic acid is an effective and well-tolerated treatment to prevent bone mineral density loss at the total hip and trochanter for up to 12 months following SCI. PMID- 20358359 TI - Nurse case-manager vs multifaceted intervention to improve quality of osteoporosis care after wrist fracture: randomized controlled pilot study. AB - Few outpatients with fractures are treated for osteoporosis in the years following fracture. In a randomized pilot study, we found a nurse case-manager could double rates of osteoporosis testing and treatment compared with a proven efficacious quality improvement strategy directed at patients and physicians (57% vs 28% rates of appropriate care). INTRODUCTION: Few patients with fractures are treated for osteoporosis. An intervention directed at wrist fracture patients (education) and physicians (guidelines, reminders) tripled osteoporosis treatment rates compared to controls (22% vs 7% within 6 months of fracture). More effective strategies are needed. METHODS: We undertook a pilot study that compared a nurse case-manager to the multifaceted intervention using a randomized trial design. The case-manager counseled patients, arranged bone mineral density (BMD) tests, and prescribed treatments. We included controls from our first trial who remained untreated for osteoporosis 1-year post-fracture. Primary outcome was bisphosphonate treatment and secondary outcomes were BMD testing, appropriate care (BMD test-treatment if bone mass low), and costs. RESULTS: Forty six patients untreated 1-year after wrist fracture were randomized to case-manager (n = 21) or multifaceted intervention (n = 25). Median age was 60 years and 68% were female. Six months post-randomization, 9 (43%) case-managed patients were treated with bisphosphonates compared with 3 (12%) multifaceted intervention patients (relative risk [RR] 3.6, 95% confidence intervals [CI] 1.1-11.5, p = 0.019). Case managed patients were more likely than multifaceted intervention patients to undergo BMD tests (81% vs 52%, RR 1.6, 95%CI 1.1-2.4, p = 0.042) and receive appropriate care (57% vs 28%, RR 2.0, 95%CI 1.0-4.2, p = 0.048). Case-management cost was $44 (CDN) per patient vs $12 for the multifaceted intervention. CONCLUSIONS: A nurse case-manager substantially increased rates of appropriate testing and treatment for osteoporosis in patients at high-risk of future fracture when compared with a multifaceted quality improvement intervention aimed at patients and physicians. Even with case-management, nearly half of patients did not receive appropriate care. TRIAL REGISTRY: clinicaltrials.gov identifier: NCT00152321. PMID- 20358360 TI - Failure to perceive increased risk of fracture in women 55 years and older: the Global Longitudinal Study of Osteoporosis in Women (GLOW). AB - We compared self-perception of fracture risk with actual risk among 60,393 postmenopausal women aged >=55 years, using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. Improved education about osteoporosis risk factors is needed. INTRODUCTION: This study seeks to compare self-perception of fracture risk with actual risk among postmenopausal women using data from GLOW. METHODS: GLOW is an international, observational, cohort study involving 723 physician practices in 17 sites in ten countries in Europe, North America, and Australia. Participants included 60,393 women >=55 years attended by their physician during the previous 24 months. The sample was enriched so that two thirds were >=65 years. Baseline surveys were mailed October 2006 to February 2008. Main outcome measures were self-perception of fracture risk in women with elevated risk vs women of the same age and frequency of risk factors for fragility fracture. RESULTS: In the overall study population, 19% (10,951/58,434) of women rated their risk of fracture as a little/much higher than that of women of the same age; 46% (27,138/58,434) said it was similar; 35% (20,345/58,434) believed it to be a little/much lower. Among women whose actual risk was increased based on the presence of any one of seven risk factors for fracture, the proportion who recognized their increased risk ranged from 19% for smokers to 39% for current users of glucocorticoid medication. Only 33% (4,185/12,612) of those with >=2 risk factors perceived themselves as being at higher risk. Among women reporting a diagnosis of osteopenia or osteoporosis, only 25% and 43%, respectively, thought their risk was increased. CONCLUSION: In this international, observational study, most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. PMID- 20358361 TI - Validation of a simple isotope method for estimating true calcium fractional absorption in adolescents. AB - We validated a single oral isotope method for estimating fractional calcium absorption determined by double isotope methods in adolescents. Developed equations with an oral isotope including a single blood draw or spot urine collection can be used to evaluate fractional calcium absorption in adolescents which allows flexibility in developing protocols. INTRODUCTION: This study was designed to develop and validate a simpler, less expensive single oral isotope method for determining fractional calcium (Ca) absorption in adolescents. METHODS: We used our database of 31 observations from ten white and 12 black adolescent girls aged 10-15 years who participated in metabolic and kinetic studies. Tracer data following oral ((44)Ca) and intravenous (IV, (42)Ca) administration of calcium stable isotopes and samples in serum and urine from various time points up to 4 days were used to develop methods using multiple regression analysis based on a single measurement of enriched stable isotope/tracee defined as tracer/tracee (TT) in serum (TT(serum)) or urine (TT(urine)). Reference values for fractional calcium absorption were from oral/IV stable isotope ratios in 24-h serum or urine and full kinetic modeling. RESULTS: The strongest equation using a single blood sample had R (2) = 0.94 (p < 0.001): fractional Ca absorption = 1.3340(4-h TT(serum))(0.7872) BSA(1.7132)e ((-0.01652 PMA)), where BSA is body surface area and PMA is post-menarcheal age. The strongest equation using a single urine sample had R (2) = 0.95 (p < 0.001): fractional Ca absorption = 2.3088 (5-12 h TT(urine))(0.8208) BSA(1.5260)e (( 0.01850 PMA)). Equations were also developed with Tanner score. An external data set of Asian adolescent boys and girls was used to validate the equations. CONCLUSION: Equations using an oral isotope and a single blood draw or urine collection for determining fractional calcium absorption were successfully validated in healthy, non-obese white and black adolescent girls aged 10-15 years. The equations well-predicted fractional calcium absorption in Asian adolescent boys and girls. PMID- 20358362 TI - An observational study of glucocorticoid-induced osteoporosis prophylaxis in a national cohort of male veterans with rheumatoid arthritis. AB - We applied regression techniques to a large cohort of patients to understand why certain patients are prescribed medications to prevent glucocorticoid-induced osteoporosis (GIO). Rates of prescriptions to prevent osteoporosis were low. The presence of drugs and disorders associated with osteoporosis and gastrointestinal conditions actually are associated with a decreased likelihood of receiving osteoporosis-preventing medications. INTRODUCTION: To understand why some patients are prescribed medications to prevent GIO while other patients are not, we examined whether there is an association among osteoporosis-inducing medical conditions or medications and prescriptions for osteoporosis prophylaxis in a large cohort of rheumatoid arthritis patients on chronic glucocorticoids. METHODS: Department of Veterans' Affairs national administrative databases were used to construct a cohort (n = 9,605) and provide the data for this study. Multivariate logistic regression was performed to determine medical conditions and medications associated with dispensing of GIO-preventive medications, controlling for sociodemographic variables, comorbidities, glucocorticoid dosage, prior fractures, and rheumatoid arthritis severity. A subanalysis examined predictors of early GIO prevention. RESULTS: Subjects were more likely to receive GIO prophylaxis if they were older, African American, treated with multiple antirheumatic disease-modifying drugs, or received greater glucocorticoid exposure. The prescription of certain drug classes (loop diuretics and anticonvulsants) and conditions (malignancy, renal insufficiency, alcohol abuse, and hepatic disease) were associated with lower likelihood of GIO prophylaxis, despite putative links between these agents/conditions and osteoporosis. The presence of gastrointestinal disorders dramatically decreased likelihood of GIO prophylaxis. Few characteristics predicted the dispensing of GIO-preventing medications within 7 days of the initial glucocorticoid start date. CONCLUSIONS: Rates of prescriptions to prevent osteoporosis in a cohort of older men with rheumatoid arthritis on chronic glucocorticoids were low. Gastrointestinal disorders and drugs and disorders potentially linked to osteoporosis are associated with diminished odds of being prescribed GIO-preventing medications. PMID- 20358363 TI - Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. AB - BACKGROUND: Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance. METHODS: We examined the effects of two drugs that cause disruptions in perception and cognition in humans-the kappa-opioid receptor (KOR) agonist salvinorin A (salvA; 0.125-4.0 mg/kg) and the non competitive NMDA receptor antagonist ketamine (0.63-20 mg/kg)-on behavior in rats using the 5-choice serial reaction time task (5CSRTT), a food-motivated test that quantifies attention. We also compared the binding profiles of salvA and ketamine at KORs and NMDA receptors. RESULTS: SalvA and ketamine produced the same pattern of disruptive effects in the 5CSRTT, characterized by increases in signs often associated with reduced motivation (omission errors) and deficits in processing (elevated latencies to respond correctly). Sessions in which rats were fed before testing suggest that reduced motivation produces a subtly different pattern of behavior. Pretreatment with the KOR antagonist JDTic (10 mg/kg) blocked all salvA effects and some ketamine effects. Binding and function studies revealed that ketamine is a full agonist at KORs, although not as potent or selective as salvA. CONCLUSIONS: SalvA and ketamine have previously under-appreciated similarities in their behavioral effects and pharmacological profiles. By implication, KORs might be involved in some of the cognitive abnormalities observed in psychiatric disorders such as schizophrenia. PMID- 20358365 TI - Hyperdense basilar artery sign diagnoses acute posterior circulation stroke and predicts short-term outcome. AB - INTRODUCTION: It is well established that the hyperdense middle cerebral artery sign is a specific marker for early ischemia in anterior circulation. However, little is known about the hyperdense basilar artery sign (HDBA) in posterior circulation. Our aim was to determine whether the HDBA sign has utility in early diagnosis of acute posterior circulation stroke and prediction of short-term outcome. METHODS: Three-blinded readers examined unenhanced computed tomography scans for the HDBA sign, and materials were classified into two groups according to this sign. Vascular risk factors, admission and discharge National Institute of Health Stroke Scale (NIHSS) scores, short-term outcome, and radiological findings between the two groups were compared. RESULTS: One hundred and twenty six cases of acute posterior circulation stroke (PCS) were included in the study. No statistically significant differences were found in risk factors of ischemic stroke, except atrial fibrillation (P=0.025). Admission and discharge NIHSS scores for the positive HDBA group were significantly higher than scores for the negative HDBA group (P=0.001, 0.002, respectively). The infarction territory for the positive HDBA group was mainly multi-region in nature (51.6%, P<0.001), while the negative HDBA group showed mainly middle territory infarction. Significant independent predictors of short-term outcome included the HDBA sign (P<0.001) and admission NIHSS scores (P<0.001). CONCLUSION: Approximately half of the HDBA patients showed multi-region infarction and a serious neurological symptom. Based on our results, this sign might not only be helpful in early diagnosis of acute PCS but also be able to correlate with a poor short-term outcome. PMID- 20358364 TI - Reinforcing effects of nicotine and non-nicotine components of cigarette smoke. AB - RATIONALE: Nicotine and non-nicotine components of cigarette smoke contribute to its reinforcing effects; however, the specific role of each component in maintaining behavior has not yet been elucidated. OBJECTIVES: To assess the reinforcing effects of nicotine and non-nicotine components of cigarette smoke by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized ("denic") cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component. METHODS: Sixteen smokers participated in seven sessions: 1) a baseline smoking assessment, used to tailor the nicotine dose per infusion; 2) two sessions for training discrimination of IV nicotine vs. saline infusions and denic smoke vs. sham puffs; and 3) four sessions assessing choice behavior after different satiation conditions. RESULTS: Denic smoke was self-administered more than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was inversely correlated with subjective ratings of "comfort" associated with nicotine. Smoke satiation reduced the number of denic puffs taken during choice periods, while prior nicotine administration did not affect puffing behavior. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke. CONCLUSIONS: In established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non nicotine factors. PMID- 20358366 TI - Diffusion-weighted magnetic resonance imaging for the detection of lipid-rich necrotic core in carotid atheroma in vivo. AB - INTRODUCTION: Research has shown that knowing the morphology of carotid atheroma improves current risk stratification for predicting subsequent thrombo-embolic events. Previous magnetic resonance (MR) ex vivo studies have shown that diffusion-weighted imaging (DWI) can detect lipid-rich necrotic core (LR/NC) and fibrous cap. This study aims to establish if this is achievable in vivo. METHODS: Twenty-six patients (mean age 73 years, range 54-87 years) with moderate to severe carotid stenosis confirmed on ultrasound were imaged. An echo-planar DWI sequence was performed along with standard high-resolution MR imaging. Apparent diffusion coefficient (ADC) maps were evaluated. Two independent readers reported the mean ADC values from regions of interest defining LR/NCs and fibrous caps. For subjects undergoing carotid endarterectomy (n = 19), carotid specimens were obtained and stained using Nile red. RESULTS: The mean ADC values were 1.0 * 10( 3) mm(2)/s (+/-SD 0.3 * 10(-3) mm(2)/s) and 0.7 * 10(-3) mm(2)/s (+/-SD 0.2 * 10( 3) mm(2)/s) for fibrous cap and LR/NC, respectively; the difference was significant (p < 0.0001). The intra-class correlation coefficients summarising the agreement between the two independent readers were 0.84 and 0.60 for fibrous cap and LR/NC, respectively. Comparison of quantitative ADC values and histology (by subjective grading of lipid content) showed a significant correlation: heavier lipid staining matched lower ADC values (r = -0.435, p = 0.005). CONCLUSIONS: This study indicates that DWI can be used to distinguish LR/NC and the fibrous cap. The study also suggests that the mean ADC value may be linearly related to subjective graded LR/NC content determined by histology. PMID- 20358367 TI - Utility of susceptibility-weighted MRI in differentiating Parkinson's disease and atypical parkinsonism. AB - INTRODUCTION: Neuropathological studies report varying patterns of brain mineralization in Parkinson's diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P. METHODS: Eleven patients with PD, 12 with PSP, 12 with MSA-P, and 11 healthy controls underwent SWI of the brain. Hypointensity of putamen, red nucleus, substantia nigra, and dentate nucleus in all groups were measured using an objective grading scale and scored from 0 to 3. RESULTS: In PSP, hypointensity score of red nucleus was higher than that in MSA-P (p=0.001) and PD (p=0.001), and a score of >= 2 differentiated the PSP group from the PD and MSA-P groups. Putaminal hypointensity score was higher in PSP when compared to that in PD (p=0.003), and a score of >= 2 differentiated PSP from PD groups. SWI hypointensity scores of red nucleus and putamen had an excellent intrarater and interrater correlation. Substantia nigra hypointensity score of the PSP group was higher than that of the MSA-P (p=0.004) and PD (p=0.006) groups, but the scores had only a moderate intrarater and interrater correlation. CONCLUSIONS: SWI shows different patterns of brain mineralization in clinically diagnosed groups of PD, PSP, and MSA-P and may be considered as an additional MR protocol to help differentiate these conditions. PMID- 20358368 TI - Understanding the role of thiol and disulfide self-assembled DNA receptor monolayers for biosensing applications. AB - A detailed study of the immobilization of three differently sulfur-modified DNA receptors for biosensing applications is presented. The three receptors are DNA (CH)n-SH-, DNA-(CH)n-SS-(CH)n-DNA, and DNA-(CH)n-SS-DMTO. Nanomechanical and surface plasmon resonance biosensors and fluorescence and radiolabelling techniques were used for the experimental evaluation. The results highlight the critical role of sulfur linker type in DNA self-assembly, affecting the kinetic adsorption and spatial distribution of DNA chains within the monolayer and the extent of chemisorption and physisorption. A spacer (mercaptohexanol, MCH) is used to evaluate the relative efficiencies of chemisorption of the three receptors by analysing the extent to which MCH can remove physisorbed molecules from each type of monolayer. It is demonstrated that -SH derivatization is the most suitable for biosensing purposes as it results in densely packed monolayers with the lowest ratio of physisorbed probes. PMID- 20358370 TI - MR-guided freehand biopsy of liver lesions with fast continuous imaging using a 1.0-T open MRI scanner: experience in 50 patients. AB - The purpose of this study was to assess a new open system with a field-strength of 1.0 T for the feasibility of liver biopsy using the freehand technique with fast continuous imaging. Fifty patients with focal liver lesions measuring 5 to 30 mm in diameter were included in the study. Guidance and monitoring was performed using a 1.0-T open magnetic resonance (MR) scanner (Panorama HFO; Philips Healthcare, Best, The Netherlands). With fast continuous imaging using a T1-weighted (T1W) gradient echo (GRE) sequence after administration of gadolinium (Gd)-EOB-DTPA, the needle was placed into the lesion. An interface for interactive dynamic viewing in two perpendicular planes prevented needle deviations T2-weighted turbo spin echo (TSE) fat-suppressed sequence was added to rule out postinterventional hematoma or biloma. All lesions were visible on the interventional images. Biopsy was technically successful, and solid specimens were obtained in all cases. Forty-six patients showed a histopathologic pattern other than native liver tissue, thus confirming correct position of the needle. Time between determination of the lesion and performance of the control scan was on average 18 min. No major complications were recorded. MR guidance with the new 1-T open system must be considered an attractive alternative for liver punction. An interface for dynamic imaging of needle guidance and T1W-GRE imaging with administration of Gd-EOB-DTPA for contrast enhancement allows the pinpoint puncture of liver lesions. PMID- 20358371 TI - Production of an in vitro-derived deletion mutation of Brevibacillus laterosporus by constructing a homology-driven integration vector. AB - In this study, a homology-driven integration vector and electroporation system was developed to delete a protease gene in the pathogenic bacterium Brevibacillus laterosporus strain G4. Furthermore, an in vitro protease-deficient mutation was generated by introducing the integration vector with a 445-bp protease BLG4 fragment into B. laterosporus chromosomal target via homologous recombination. The BLG4-deficient mutant showed a significant drop in protease activity as compared to the wild-type G4 strain, but had a slight effect on bacterial growth and sporulation. The results revealed that the developed method can become an important tool for studying the molecular pathogenesis mechanisms of B. laterosporus. PMID- 20358372 TI - Osmoregulated periplasmic glucan polymerization requires constant protein synthesis in Escherichia coli. AB - Osmoregulated periplasmic glucans are a family of oligosaccharides found in the periplasm of Gram negative bacteria. Mutants devoid of OPGs show strong reduction or absence of virulence on their hosts and display pleiotropic phenotype. Glucose is the sole constituent sugar and OPG level increases as the osmolarity of the medium decreases. OPG synthesis is regulated both at the transcriptional and at the enzymatic level. Data presented in this article indicate that in addition, OPG synthesis requires constant synthesis of protein indicating rapid turnover of one of the two proteins catalyzing glucose backbone of OPGs. PMID- 20358373 TI - Growth, Fe3+ reductase activity, and siderophore production by Paenibacillus polymyxa SQR-21 under differential iron conditions. AB - An experiment was planned to evaluate the behavior of Paenibacillus polymyxa SQR 21 under differential iron availability. P. polymyxa was grown under three differential iron conditions (0, 2, 20 MUM). Iron starvation slowed bacterial growth and at all iron levels, pH of liquid culture was decreased, but maximum decrease was observed at highest iron level. Cell surface ferrireductase activity decreased as culture aged, while extracellular Fe(3+)-reducing activity constantly increased. Hydroxamates type siderophores production was increased with the decrease in iron levels. Numerous cellular proteins were expressed by P. polymyxa in the range of 5-140 kDa and several of them showed conspicuous differential iron regulation. P. polymyxa seems to have more than one type of iron acquisition mechanism including gradual release of organic acids, cell surface ferrireductases, extracellular reductants, and secretion of low molecular weight hydroxamates chelators. This article is the first to report the kinetic study of P. polymyxa under differential iron availability. The information provided here gives initial information about the iron uptake mechanism of P. polymyxa. PMID- 20358374 TI - SCAR makers and multiplex PCR-based rapid molecular typing of Lentinula edodes strains. AB - Lentinula edodes is the second most important cultivated mushroom worldwide, the most commercial strains have been identified only through traditional phenotypic analysis. In this study, a simple rapid PCR-based molecular method was developed for distinguishing commercial strains of L. edodes by developing specific sequence characterized amplified region (SCAR) markers and establishing multiplex PCR assays with the SCAR primers. Derived from the randomly amplified polymorphic DNA (RAPD) and sequence-related amplified polymorphism (SRAP) techniques, 10 informative SCAR markers were generated from 10 polymorphic RAPD and SRAP bands. The differences in SCAR phenotypes among different strains made these SCAR markers potentially useful to characterize 6 strains and identify them from other studied strains. Moreover, different SCAR phenotypes also made the other 17 studied strains to be divided into four distinguishable groups. The multiplex PCR assays were further established for the joint use of some SCAR markers efficiently. Compared with some identification methods reported previously, the special feature of this new molecular method is technically rapid and convenient in the practical use and suitable for analyzing large numbers of samples. Thus, the simple rapid PCR-based molecular method can be used as a helpful assistant tool for the lentinula industry. To our knowledge, this study is the first to describe a development of a new SCAR maker-based multiplex PCR assay for rapid molecular typing of edible mushroom. PMID- 20358375 TI - Expression of Vitreoscilla hemoglobin enhances cell growth and dihydroxyacetone production in Gluconobacter oxydans. AB - Dihydroxyacetone (DHA) is an important ketose sugar, which is extensively used in the cosmetic, chemical, and pharmaceutical industries. DHA has been industrially produced by Gluconobacter oxydans with a high demand of oxygen. To improve the production of DHA, the gene vgb encoding Vitreoscilla hemoglobin (VHb) was successfully introduced into G. oxydans, where it was stably maintained, and expressed at about 76.0 nmol/g dry cell weight. Results indicated that the constitutively expressed VHb improved cell growth and DHA production in G. oxydans under different aeration conditions. Especially at low aeration rates, the VHb-expressing strain (VHb(+)) displayed 23.13% more biomass and 37.36% more DHA production than those of VHb-free strain (VHb(-)) after 32 h fermentation in bioreactors. In addition, oxygen uptake rate (OUR) was also increased in VHb(+) strain relative to the control strain during fermentation processes. PMID- 20358376 TI - An account describing an operation for the bullet extraction from the middle of 17th century Ottoman traveller Evliya Celebi (1611-1682 AD: ). PMID- 20358378 TI - Ahp2 (Hop2) function in Arabidopsis thaliana (Ler) is required for stabilization of close alignment and synaptonemal complex formation except for the two short arms that contain nucleolus organizer regions. AB - A cytological comparative analysis of male meiocytes was performed for Arabidopsis wild type and the ahp2 (hop2) mutant with emphasis on ahp2's largely uncharacterized prophase I. Leptotene progression appeared normal in ahp2 meiocytes; chromosomes exhibited regular axis formation and assumed a typical polarized nuclear organization. In contrast, 4',6'-diamidino-2-phenylindole stained ahp2 pachytene chromosome spreads demonstrated a severe reduction in stabilized pairing. However, transmission electron microscopy (TEM) analysis of sections from meiocytes revealed that ahp2 chromosome axes underwent significant amounts of close alignment (44% of total axis). This apparent paradox strongly suggests that the Ahp2 protein is involved in the stabilization of homologous chromosome close alignment. Fluorescent in situ hybridization in combination with Zyp1 immunostaining revealed that ahp2 mutants undergo homologous synapsis of the nucleolus-organizer-region-bearing short arms of chromosomes 2 and 4, despite the otherwise "nucleus-wide" lack of stabilized pairing. The duration of ahp2 zygotene was significantly prolonged and is most likely due to difficulties in chromosome alignment stabilization and subsequent synaptonemal complex formation. Ahp2 and Mnd1 proteins have previously been shown, "in vitro," to form a heterodimer. Here we show, "in situ," that the Ahp2 and Mnd1 proteins are synchronous in their appearance and disappearance from meiotic chromosomes. Both the Ahp2 and Mnd1 proteins localize along the chromosomal axis. However, localization of the Ahp2 protein was entirely foci-based whereas Mnd1 protein exhibited an immunostaining pattern with some foci along the axis and a diffuse staining for the rest of the chromosome. PMID- 20358377 TI - Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges. AB - BACKGROUND: In tuberous sclerosis complex (TSC), a substantially increased risk of developing epilepsy is present as a result of a disruption of a TSC gene expression in the brain and secondary abnormal cellular differentiation, migration, and proliferation. Dysregulated excitation probably has its roots in the disruption of GABAergic interneuron development. There is an age-dependent electroclinical expression of seizures, and epilepsy is often quite severe and unremitting. DISCUSSION: The majority of patients (>60%) who are candidates for surgery remain seizure-free after tuberectomy. During the recent years technical advances in the localization of the epileptogenic zone during the recent years have lead to a 63% of Engel class I status after surgery compared with a previous 52%. In medically refractory patients not suitable for surgery, vagus nerve stimulation has proved efficacy in significantly reducing seizure frequency in more than 50% of cases. New evidence suggests that mTOR inhibitors may be helpful in the management of intractable epilepsy for individuals with TSC. PMID- 20358379 TI - Cancer mortality study among French cement production workers. AB - PURPOSE: To analyse the mortality and its causes, especially cancer, among French cement production workers. METHODS: A cohort of all workers employed at least 1 year in one of the main four cement companies in France was assembled (9,118 workers, 122,124 person-years of follow-up between 1990 and 2005). A common job titles classification was used to analyse occupational risk factors. We conducted a standardized mortality ratio analysis based on age, gender and calendar-period specific national mortality rates and explored the combined effect of job titles and duration through an internal Cox regression analysis. RESULTS: The number of deaths during the follow-up period was 430 (4.7%). Malignant neoplasm was the cause of 48.1% of deaths. Overall, a deficit in all-causes mortality (standardized mortality ratio (SMR): 0.68, 95% confidence interval (CI) 0.61 0.74) and in cancer mortality (SMR: 0.80, CI 0.69-0.92) was observed. Working in the quarry, yard and shipping sectors was associated with a 50% higher all-causes mortality risk in comparison with the administrative sector. CONCLUSIONS: This cohort study does not support previous observations that cement workers are at higher risk of cancer mortality than the general population. The length of follow up should be increased, and specific exposures deserve analysis. PMID- 20358380 TI - Prognostic factors affecting survival and recurrence after hepatic resection for hepatocellular carcinoma in cirrhotic liver. AB - AIM: Hepatic resections for hepatocellular carcinoma (HCC) in cirrhotic liver are characterized by early recurrence and poor survival. In this study, we analyzed several factors affecting both survival and recurrence after hepatic resection. PATIENTS AND METHODS: From October 1995 to April 2007, 550 patients underwent hepatic resections, of which, 175 patients had HCC in cirrhotic liver in Gastroenterology Surgical Center, Mansoura University, Egypt. There were 131 males (74.9%) and 44 females (25.1%) with a mean age of 54.8 +/- 9.2 years (ranges from 26 to 75 years). RESULTS: Most of our patients were in Child's Pugh class A (86.9%). Major hepatic resection was done for 65 patients (37.1%), segmentectomy was done for 62 patients (35.4%), and localized resection was done for 48 patients (27.4%). Hospital mortality occurred in 16 (9.1%) patients, while hospital morbidity occurred in 40% of patients. The 1, 3, and 5 years survival were 68.6%, 29.6%, and 10.7%, respectively. The prognostic factors affecting recurrence were multifactorial, and the univariate analysis showed that multifocality of the tumor (p = 0.006), capsule (p = 0.001), staging (p = 0.001), blood transfusion (p = 0.02), infiltration of the cut margin (p = 0.001), vascular invasion (p = 0.006), and lymph nodes infiltration (p = 0.014) affect the recurrence rate, while with multivariate analysis, only cut margin was significantly affecting the recurrence (p = 0.026). Also, factors that significantly predicted survival were preoperative serum albumin (p = 0.005), tumor differentiation (p = 0.008), staging (p = 0.001), tumor's capsule (p = 0.001), cut margin (p = 0.031), vascular invasion (p = 0.049), and operative blood transfusion (p = 0.001). However, tumor differentiation (p = 0.048) was the only independent factor on multivariate analysis affecting long-term survival. CONCLUSION: In our experience, the prognostic factors after resection for recurrence and survival are different and multifactorial. However, resection of HCC in cirrhotic liver with preserved liver function is the treatment of choice in the present time and can be done with favorable results. PMID- 20358381 TI - Evaluation of UICC-TNM and JSBS staging systems for surgical patients with extrahepatic cholangiocarcinoma. AB - AIM: Two staging systems exist to classify extrahepatic cholangiocarcinoma (EHC), the TNM staging of the International Union Against Cancer (UICC) and the classification system of the Japanese Society of Biliary Surgery (JSBS). This study sought to evaluate the utility of these two staging systems. METHOD: One hundred and twenty eight consecutive patients who underwent surgical resection were retrospectively classified into the appropriate stages using the UICC-TNM and JSBS systems. We also compared the distribution and survival curves of respective stages. RESULTS: Although the UICC-TNM staging system divided patients into seven categories, 106 of 128 patients (82.8%) fell into three stages (stages IA, IIA, or IIB). In contrast, patients were relatively evenly divided across the five categories in JSBS staging. The survival curve of UICC-TNM stage IIB was more similar to stage IV than stages IIA or III; survival rates for stages IIB and IV were significantly lower than the other stages. According to the JSBS staging system, there were significant differences between stages I and III, IVA and IVB, and II and IVA/IVB, and III and IVA/IVB. CONCLUSIONS: Patients who underwent surgical resection were not evenly divided across UICC-TNM staging categories in comparison to JSBS staging. Stratification of survival ability was better when using the JSBS staging in comparison to the UICC-TNM system. The better understanding about distribution of patient classified by stage and stratification ability of survival of these two staging system may help surgeons assess the patients with EHC. PMID- 20358382 TI - The dynamic locking screw (DLS) can increase interfragmentary motion on the near cortex of locked plating constructs by reducing the axial stiffness. AB - BACKGROUND: The plate-screw interface of an angular stable plate osteosynthesis is very rigid. So far, all attempts to decrease the stiffness of locked plating construct, e.g. the bridged plate technique, decrease primarily the bending stiffness. Thus, the interfragmentary motion increases only on the far cortical side by bending the plate. To solve this problem, the dynamic locking screw (DLS) was developed. MATERIALS AND METHODS: Comparison tests were performed with locking screws (LS) and DLS. Axial stiffness, bending stiffness and interfragmentary motion were compared. For measurements, we used a simplified transverse fracture model, consisting of POM C and an 11-hole LCP3.5 with a fracture gap of 3 mm. Three-dimensional fracture motion was detected using an optical measurement device (PONTOS 5 M/GOM) consisting of two CCD cameras (2,448 x 2,048 pixel) observing passive markers. RESULTS: The DLS reduced the axial stiffness by approximately 16% while increasing the interfragmentary motion at the near cortical side significantly from 282 microm (LS) to 423 microm (DLS) applying an axial load of 150 N. CONCLUSION: The use of DLS reduces the stiffness of the plate-screw interface and thus increases the interfragmentary motion at the near cortical side without altering the advantages of angular stability and the strength. PMID- 20358383 TI - Comparison of gene expression in hepatocellular carcinoma, liver development, and liver regeneration. AB - Proliferation of liver cells can be observed in hepatocarcinogenesis, at different stages of liver development, and during liver regeneration after an injury. Does it imply that they share similar molecular mechanisms? Here, the transcriptional profiles of hepatocellular carcinoma (HCC), liver development, and liver regeneration were systematically compared as a preliminary attempt to answer this question. From the comparison, we found that advanced HCC mimics early development in terms of deprived normal liver functions and activated cellular proliferation, but advanced HCC and early development differ in expressions of cancer-related genes and their transcriptional controls. HCC and liver regeneration demonstrate different expression patterns as a whole, but regeneration is similar to dysplasia (pre-stage of HCC) in terms of their proximity to the normal state. In summary, of these three important processes, the carcinogenic progress carries the highest variance in expression; HCC pre stage shares some resemblance with liver regeneration; and advanced HCC stage displays similarity with early development. PMID- 20358385 TI - Rise and fall of plant mitochondria. PMID- 20358384 TI - Zoledronic acid and atrial fibrillation in cancer patients. AB - BACKGROUND AND PURPOSE: Treatment with a bisphosphonate was found to be associated with a significantly increased risk for atrial fibrillation (AF) in a few studies. A recent study showed that once-yearly infusions of intravenous zoledronic acid (ZA) significantly increased the risk of serious AF in postmenopausal women with osteoporosis. This study was conducted to determine the frequency of atrial fibrillation among cancer patients receiving the standard treatment of ZA. METHODS: Patients with bone metastases who presented to our outpatient clinic for any reason (routine control, chemotherapy, or ZA administration) were included in the study. All patients had been receiving 4 mg ZA at 4-week intervals, with each dose administered over 15 min. A short survey was completed and standard 12-lead ECG recordings were obtained. RESULTS: One hundred and twenty-four cancer patients with documented bone metastases were evaluated. Mean age of the patients was 55 +/- 13.0 years, 60% of the patients were female. Forty-one percent of the patients had breast cancer, 18% had non small cell lung cancer, and the remainder had other solid tumors. Mean duration of ZA administration was 13.4 +/- 15.0 months. Mean total cumulative dose was 54 +/- 15.0 mg per patient. Sixty patients (48%) had previously been treated with anthracycline-containing regimens, and 37 (30%) had received chest radiotherapy that might affect the heart. Twenty-three percent of the patients had hypertension, 10% had diabetes mellitus, 3.7% had myocardial infarction history, 1.9% had congestive heart failure, and 1% had valvular disease; 10.5% were current smokers and 32% ex-smokers. On ECG evaluation, we observed normal sinus rhythm in 58%, sinus tachycardia in 15%, sinus bradicardia in 3.2%, and ventricular extrasystole in 5.7% of the patients. There was no AF in any of the cases. CONCLUSIONS: There was no increase in the risk of AF frequency in cancer patients who were treated with intravenous ZA, although most of the patients had additional risk factors including previous treatment with cardiotoxic agents or with chest radiotherapy. We believe that the risk of AF is negligible in this patient population and does not affect treatment decisions. PMID- 20358386 TI - Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models. AB - Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms. PMID- 20358388 TI - Peritonitis following stapling of a flush ileostomy. AB - Peritonitis following staple stabilization of a flush ileostomy has not yet been reported in the literature. We report a case of iatrogenic injury to a loop of the ileum in an unrecognized parastomal hernia which caused peritonitis after stapling of a flush ileostomy. PMID- 20358387 TI - Analysis of NF1 somatic mutations in cutaneous neurofibromas from patients with high tumor burden. AB - Neurofibromatosis type 1, (NF1) is a complex, autosomal dominant disorder characterized by benign and malignant tumors which result from NF1 gene mutations. The molecular mechanisms that underlie NF1 tumorigenesis are still poorly understood although inactivation of other modifying loci in conjunction with NF1 mutations is postulated to be involved. These modifying loci may include deficiencies in mismatch repair genes and elements involved in cell cycle regulation (TP53, RB1, and CDKN2A). We have analyzed the somatic mutations in 89 cutaneous neurofibromas derived from three unrelated NF1 patients with high tumor burden, by loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, and CDKN2A genes, by assessing microsatellite instability (MSI), by direct sequencing of the NF1, TP53, and several mismatch repair (MMR) genes and by multiplex ligation-dependent probe amplification of the NF1 and TP53 genes. The aim was both to assess the possible clonality of these tumors and also to assess the involvement of other potential genetic loci in the development of these neurofibromas. Somatic NF1 mutations were identified in 57 (64%) of neurofibroma samples. Each mutation was distinct demonstrating the independent origin of each tumor. While somatic LOH of the TP53 gene was identified in four tumors, no specific deletions or sequence variations were identified. LOH of markers flanking the RB1 gene was also found in one tumor but no CDKN2A mutations were detected. Although evidence of MSI was seen in 21 tumors, no MMR gene alterations were identified. The identification of LOH involving TP53 and RB1 loci is a novel finding in benign cutaneous neurofibromas possibly demonstrating an alternative underlying molecular mechanism associated with the development of these benign tumors from this cohort of patients. PMID- 20358389 TI - Effect of counterions on the Rayleigh-Plateau instability of a charged cylinder. AB - The effect of counterions on the instability of a charged cylinder is investigated. Both axisymmetric and asymmetric perturbations are considered. The analysis shows that the Rayleigh-Plateau instability is modified for a charged cylinder in the presence of counterions. For the axisymmetric instability, the counterions have a stabilizing effect at low values of kappa, the inverse Debye layer thickness. However, the effect is destabilizing at higher values of kappa . The asymmetric modes which are stable for an uncharged cylinder are rendered unstable at high values of kappa . The analysis should be important in pearling instability of charged cylindrical vesicles. The expression for the correlation time of thermally induced shape fluctuations of charged cylindrical vesicles is also derived. PMID- 20358390 TI - A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate. AB - OBJECTIVE AND DESIGN: Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. SUBJECTS: Eight healthy subjects were recruited for this study. TREATMENT: Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. METHODS: Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. RESULTS: SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. CONCLUSIONS: SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS induced inflammation may be a useful model for studying the mechanisms of inflammatory pain. PMID- 20358391 TI - Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals. AB - The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity. PMID- 20358392 TI - What is it exactly that you do? An introduction. PMID- 20358393 TI - Potential role of ticks as vectors of bluetongue virus. AB - When the first outbreak of bluetongue virus serotype 8 (BTV8) was recorded in North-West Europe in August 2006 and renewed outbreaks occurred in the summer of 2007 and again in 2008, the question was raised how the virus survived the winter. Since most adult Culicoides vector midges are assumed not to survive the northern European winter, and transovarial transmission in Culicoides is not recorded, we examined the potential vector role of ixodid and argasid ticks for bluetongue virus. Four species of ixodid ticks (Ixodes ricinus, Ixodes hexagonus, Dermacentor reticulatus and Rhipicephalus bursa) and one soft tick species, Ornithodoros savignyi, ingested BTV8-containing blood either through capillary feeding or by feeding on artificial membranes. The virus was taken up by the ticks and was found to pass through the gut barrier and spread via the haemolymph into the salivary glands, ovaries and testes, as demonstrated by real-time reverse transcriptase PCR (PCR-test). BTV8 was detected in various tissues of ixodid ticks for up to 21 days post feeding and in Ornithodoros ticks for up to 26 days. It was found after moulting in adult Ixodes hexagonus and was also able to pass through the ovaries into the eggs of an Ornithodoros savignyi tick. This study demonstrates that ticks can become infected with bluetongue virus serotype 8. The transstadial passage in hard ticks and transovarial passage in soft ticks suggest that ticks have potential vectorial capacity for bluetongue virus. Further studies are required to investigate transmission from infected ticks to domestic livestock. This route of transmission could provide an additional clue in the unresolved mystery of the epidemiology of Bluetongue in Europe by considering ticks as a potential overwintering mechanism for bluetongue virus. PMID- 20358394 TI - Modulation of inflammasome activity for the treatment of auto-inflammatory disorders. AB - INTRODUCTION: The innate immune system orchestrates inflammatory responses to microorganisms or danger-associated molecular patterns generated, for example, by the deposition of uric acid in the joints of gout patients. The innate immune system comprises multiple germ-line encoded receptors, of which the nucleotide binding domain and leucine-rich repeat containing receptors (NLRs) are crucial for the maturation of pro-inflammatory cytokines. NLRs oligomerize to form large multi-protein complexes termed inflammasomes that generate active caspase-1 fragments leading to the cleavage and secretion of mature cytokines such as IL 1beta and IL-18. THE REGULATION OF MULTIPLE INFLAMMASOMES: At least four independent inflammasomes have been identified, NLRP1, NLRP3, IPAF, and AIM2. These inflammasomes assemble in response to different stimuli to confer specificity and are also subject to negative regulatory mechanisms to ensure that once a productive inflammatory response has been mounted, inflammatory cytokine production is restrained. TREATMENT OF AUTO-INFLAMMATORY DISORDERS: A number of human conditions are characterized by unrestrained inflammasome activation. As much is now known about how inflammasomes are regulated, it is hoped that this can be channeled into the development of novel therapeutics, for example, those that may block the upstream activation and assembly of inflammasomes. PMID- 20358395 TI - Joint effects of child temperament and maternal sensitivity on the development of childhood obesity. AB - The interplay between child characteristics and parenting is increasingly implicated as crucial to child health outcomes. This study assessed the joint effects of children's temperamental characteristics and maternal sensitivity on children's weight status. Data from the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development were utilized. Infant temperament, assessed at child's age of 6 months by maternal report, was categorized into three types: easy, average, and difficult. Maternal sensitivity, assessed at child's age of 6 months by observing maternal behaviors during mother-child semi-structured interaction, was categorized into two groups: sensitive and insensitive. Children's height and weight were measured longitudinally from age 2 years to Grade 6, and body mass index (BMI) was calculated. BMI percentile was obtained based on the Centers for Disease Control and Prevention's BMI charts. Children, who had a BMI >= the 85th percentile, were defined as overweight-or-obese. Generalized estimating equations were used to analyze the data. The proportions of children overweight-or-obese increased with age, 15.58% at 2 years old to 34.34% by Grade 6. The joint effects of children's temperament and maternal sensitivity on a child's body mass status depended on the child's age. For instance, children with difficult temperament and insensitive mothers had significantly higher risks for being overweight-or-obese during the school age phase but not during early childhood. Specific combinations of child temperament and maternal sensitivity were associated with the development of obesity during childhood. Findings may hold implications for childhood obesity prevention/intervention programs targeting parents. PMID- 20358396 TI - Genetics of learning abilities and disabilities: recent developments from the UK and possible directions for research in China. 2008. PMID- 20358397 TI - The end of behavioral genetics? 2008. PMID- 20358398 TI - The early growth and development study: using the prospective adoption design to examine genotype-environment interplay. 2008. PMID- 20358400 TI - Isolation and characterization of Indian isolates of camel pox virus. AB - In this study, we isolated and identified three camel pox viruses (CMLV) from two outbreaks of camel pox infection in camels associated with eruptions on cheeks, nostrils, limbs, scrotum, and sheath that occurred at different places of Bikaner district, Rajasthan (India). The scab specimens collected were subjected for virus isolation in Vero cell culture, and the isolated viruses were characterized by employing polymerase chain reaction (PCR) and sequencing. The causative agent was identified as CMLV, based on A-type inclusion, B5R and C18L genes-specific PCRs and partial sequencing of these genes, which clearly confirmed that the outbreaks were caused by CMLV and identity of CMLV isolates. Further, phylogenetic analysis of partial C18L gene sequences have showed that Indian CMLV are clustered together with other reported isolates/strains. PMID- 20358399 TI - Probing the meiotic mechanism of intergenomic exchanges by genomic in situ hybridization on lampbrush chromosomes of unisexual Ambystoma (Amphibia: Caudata). AB - The meiotic mechanism of unisexual salamanders in the genus Ambystoma was previously explained by observing lampbrush chromosomes (LBCs). In polyploid unisexual females, a pre-meiotic endomitotic event doubles the chromosome number so that, after meiotic reduction, the mature eggs have the same ploidy as the female. It was assumed that synapses during meiotic I prophase, which result in observed bivalents, join duplicated sister chromosomes. Previous studies also found LBC quadrivalents in some oocytes that could be explained by occasional synapses between homologs. The discovery of widespread intergenomic exchanges among unisexual populations has prompted new speculations on this meiotic mechanism. Synapses that involve homeologous chromosomes may be frequent during meiosis and could be responsible for intergenomic exchanges and the high embryonic mortality of unisexuals. Furthermore, LBC quadrivalents may be established by associations between homeologous rather than homologous chromosomes. The present study investigated these two important aspects pertaining to the mechanism of intergenomic exchanges: the frequency of homeologous synapses and the relationship between homeologous associations and meiotic quadrivalents. We applied genomic in situ hybridization (GISH) on LBCs from oocytes of 14 triploid and two tetraploid unisexual females. Homeologous bivalents were not observed, and all 13 LBC quadrivalents that we found were the result of homologous synapses and were not associated with any homeologous or exchanged LBCs. Intergenomic exchanges were used as markers to compare the same chromosomes at meiotic diplotene and mitotic metaphase stages. We conclude that contemporary intergenomic exchanges are very rare, and no direct link exists between intergenomic exchanges and high embryonic mortality. The actual mechanisms and evolutionary implications of intergenomic exchanges appear to be complicated and difficult to assess. The application of GISH-type molecular cytogenetic techniques will help to improve our understanding of the role that intergenomic interactions play in the persistence of unisexual Ambystoma and other unisexual vertebrates. PMID- 20358401 TI - Efficiency of methods applied for goat estrous synchronization in subtropical monsoonal climate zone of Southwest China. AB - Two experiments were undertaken to select the efficient method applied for goat estrous synchronization. In experiment 1, a total of 120 does (Capra hircus) were divided into five groups with a randomized block design, and the does of treatment 1 were synchronized by intravaginal sponges impregnated with 30 mg Levonorgestrel inserted for 10 days. Does of treatments 2, 3, and 4 were treated with further injection of 25 IU follicle-stimulating hormone (FSH), 0.05 mg prostaglandin F2 alpha (PGF(2alpha)), and 25 IU FSH + 0.05 mg PGF(2alpha) at sponge withdrawal, respectively. The does in the control group (n = 40) without estrous synchronization treatment and natural estrous does were observed. In experiment 2, a total of 140 does in five goat farms in breeding and non-breeding seasons were treated with the selective efficient procedure. The results presented that all the employed treatments were capable of inducing and synchronizing estrous goats. According to estrous response and economy, the use of intravaginal sponges impregnated with 30 mg Levonorgestrel and 0.05 mg PGF(2alpha) (treatment 3) is the first choice for estrous synchronization, and 95.0% of synchronized does demonstrated estrus, which was significantly higher than that of treatment 1 (P < 0.05) and control group (P < 0.01). The percentages of ovulating of treatments 3 and 4 were the same (95.0%), which were significantly higher than that of treatment 1 (P < 0.01). The ovulation rates among different groups were not significant (P > 0.05). When the selective procedure was applied to five goat farms, 85.7% (120/140) of does demonstrated estrus, and the kidding percentage, litter size, and prolificacy rate were 53.6%, 0.95, and 177%, respectively. PMID- 20358402 TI - Estimation of goat production potential and efficiency in the resource-poor communal areas of the Eastern Cape Province of South Africa. AB - It is often inappropriately assumed that the contributions of goats to household economies are similar across flock sizes. A monthly questionnaire was administered to 19, 21, and 13 farmers in Matatiele and Qawukeni and Mankone. Entries and exits to and from each flock were assessed. Most (P < 0.05) kids were born in August (4.92 +/- 0.362 and 2.03 +/- 0.329 for large and small flocks, respectively). Total entries were higher (P < 0.05) in August, September, and October than in the other months. Kid mortality peaked in May and September at 21%. Most (P < 0.05) goats were sold in December (1.06 +/- 0.127 for large flocks and 0.23 +/- 0.135 for small flocks). Goat production efficiency (GPE) was affected (P < 0.05) by month and flock size. The GPE was higher (P < 0.05) in small than in large flocks. The low GPE values obtained in this study indicates the need to devise other indices that factor in the neglected functions of goats when measuring goat production efficiency in communities where the main function of goats is not for sale or consumption. PMID- 20358403 TI - Efficiency of two timed artificial insemination protocols in Murrah buffaloes managed under a semi-intensive system in the tropics. AB - The objective of the study was to determine the efficiency of ovsynch (OV) versus presynch-ovsynch (P-OV) protocol for synchronization of ovulation and timed artificial insemination (TAI) in female buffaloes. The OV group (n = 40) received gonadotrophin-releasing hormone (GnRH) on day 0 (random day of the estrous cycle), prostaglandin PGF2alpha on day 7 and a second GnRH administration on day 9 followed by a single artificial insemination (AI) 16-20 h later. The P-OV group (n = 40) received two PGF2alpha injections 14 days apart, with the second injection administered 14 days before starting the OV protocol. Progesterone (P(4)) was measured at the time of PGF2alpha administration (within the OV protocol) and AI. Neither ovulation rate ((24 h after TAI) OV 90%-36/40 vs. P-OV 85%-34/40) nor pregnancy rates ((day 60 after TAI) OV 35%-14/40 vs. P-OV 45% 18/40) differed between the two protocols. Pregnant buffaloes had lower concentrations of P(4) at AI compared with non-pregnant animals in the OV group (0.7 +/- 0.1 vs. 1.1 +/- 0.1 ng/ml); but in the P-OV group, differences did not reach statistical significance (0.8 +/- 0.1 vs. 1.0 +/- 0.1 ng/ml). This apparent trend reached statistical significance when the analysis was carried out in animals from both protocols (0.7 +/- 0.1 (pregnant) vs. 1.1 +/- 0.1 (non pregnant) ng/ml). In conclusion, both protocols synchronize ovulation effectively with no significant differences in conception rates. High concentrations of P(4) at AI seem to be detrimental for the establishment of pregnancy in lactating buffalo cows. PMID- 20358405 TI - Theoretical and practical problems with wide reflective equilibrium in bioethics. AB - Various theories have been put forward in an attempt to explain what makes moral judgments justifiable. One of the main theories currently advocated in bioethics is a form of coherentism known as wide reflective equilibrium. In this paper, I argue that wide reflective equilibrium is not a satisfactory approach for justifying moral beliefs and propositions. A long-standing theoretical problem for reflective equilibrium has not been adequately resolved, and, as a result, the main arguments for wide reflective equilibrium are unsuccessful. Moreover, practical problems that arise in using the method of wide reflective equilibrium undermine the idea that it is a viable approach for justifying moral judgments about cases and policies. Given that wide reflective equilibrium is the most prominent version of coherentism, these considerations call into question the coherentist approach to justification in bioethics. PMID- 20358404 TI - Implementation of guidelines for sequential therapy with fluoroquinolones in a Belgian hospital. AB - OBJECTIVE: This study measured the impact of three interventions for physicians, in order to implement guidelines for sequential therapy (intravenous to oral conversion) with fluoroquinolones. SETTING: A Belgian university hospital with 1,065 beds. Method The first intervention consisted of the hospital-wide publication of guidelines in the local drug letter towards all prescribers. The consumption of fluoroquinolones was measured by means of an interrupted time series (ITS) analysis 21 months before (period A) and 24 months after publication (period B). The second intervention was an educational interactive session, by infectious disease specialists, to the medical staff of orthopaedics and endocrinology. The third intervention comprised a proactive conversion programme on the abdominal surgery, gastro-enterology and plastic surgery wards, where pharmacists attached a pre-printed note with a suggestion to switch to an oral treatment every time a patient met the criteria for switching. The second and third intervention took place 6 months after the first intervention. Fluoroquinolone treatments were evaluated during a 2 month period before (group 1) and after the introduction of the second (group 2) and third (group 3) intervention. MAIN OUTCOME MEASURE: The monthly ratio of intravenous versus total fluoroquinolone consumption (daily defined doses per 1,000 bed days) was measured to assess the impact of the first intervention. The impact of the second and third intervention was measured in relation to the number of days that intravenous therapy continued beyond the day that the patient fulfilled the criteria for sequential therapy and the antibiotic cost. RESULTS: The ITS demonstrated a reduction of 3.3% in the ratio of intravenous versus total consumption after the publication of the guidelines (P = 0.011). In group 1, patients were treated intravenously for 4.1 days longer than necessary. This parameter decreased in group 2 to 3.5 days and in group 3 to 1.0 day (P = 0.006). The mean additional cost for longer intravenous treatment decreased from 188.0 euro in group 1, to 103.0 euro in group 2 and 44.0 euro in group 3 (P = 0.037). CONCLUSION: This study demonstrated that active implementation of guidelines is necessary. A proactive conversion programme by a pharmacist resulted in a reduction in the duration of the intravenous treatment, and the treatment cost. PMID- 20358406 TI - The reliability and validity of the Korean version of the Epworth sleepiness scale. AB - OBJECTIVE: The Epworth sleepiness scale (ESS) is widely used to measure the subject's average sleep propensity across those different situations in daily life, particularly in patients with sleep-disordered breathing. The purposes of this study were to test the hypothesis that the Korean version of the ESS (KESS) is valid and evaluate its usefulness. MATERIALS AND METHODS: We developed the KESS, which involved translating into Korean and then translating back into English to check its accuracy. A total of 273 participants (181 obstructive sleep apnea (OSA)-37 mild, 61 moderate, 83 severe, 32 simple snoring and 60 normal) were included in this study. All subjects completed the overnight polysomnograph and 53 of the total subjects were randomly selected for a retest with the questionnaire approximately 2~4 weeks later. The associations between KESS and the degree of OSA were examined through ANCOVA, adjusted for age, sex and BMI. RESULTS: The total score and each item's score of KESS in patients with OSA were significantly higher than subjects with normal controls (p < 0.01). As the severity of OSA increased, the KESS showed significantly increasing patterns (p for trend <0.01). The KESS in patient groups showed good internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (r = 0.78 to 0.93). CONCLUSION: The KESS is a reliable and valid tool for screening patients with daytime sleepiness in Korea. PMID- 20358407 TI - Minimally invasive esophagectomy for Barrett's with high-grade dysplasia and early adenocarcinoma of the esophagus. PMID- 20358408 TI - Beta-D-galactosidase from Enterobacter cloacae: production and some physicochemical properties. AB - A bacterial strain isolated from soil and identified as Enterobacter cloacae had been found to be capable of producing both intra and extracellular beta-D: galactosidase.The intracellular enzyme was thermostable and its optimum temperature, pH and time for enzyme-substrate reaction were found to be 50 degrees C, 9.0 and 5 min respectively, using ONPG as substrate. The maximum beta galactosidase production in shake flask was achieved at 30 degrees C, pH 7.0, incubation time 72 h using 50 ml medium in 250 ml Erlenmeyer flask. Only Mg(2+) stimulated the activity of enzyme. Cetyl trimethyl ammonium bromide showed stimulatory effect on catalytic activity of the enzyme whereas EDTA inhibited enzyme activity. The enzyme retained its activity upto 55 degrees C after incubating at that temperature for 1 h.The maximum activity of crude intracellular enzyme was 14.35 IU/mg of protein. The K (m) and V (max) values of beta-galactosidase using ONPG as substrate at 50 degrees C were 2.805 mM and 37.45 x 10(-3) mM/min/mg, respectively. PMID- 20358409 TI - Potential of biocellulose nanofibers production from agricultural renewable resources: preliminary study. AB - In the present preliminary study, we report results for the biocellulose nanofibres production by Gluconacetobacter xylinus. Production was examined by utilizing different feedstocks of single sugars and sugar mixtures with compositions similar to the acid hydrolyzates of different agriculture residues. Profiles for cell proliferation, sugar consumption, and the subsequent pH changes were thoroughly analyzed. Highest biocellulose production of 5.65 g/L was achieved in fructose medium with total sugar consumption of 95.57%. Moreover, the highest production using sugar mixtures was 5.2 g/L, which was achieved in feedstock with composition identical to the acid hydrolyzate of wheat straws. This represented the highest biocellulose yield of 17.72 g/g sugars compared with 14.77 g/g fructose. The lowest production of 1.1 and 1.75 g/L were obtained in xylose and glucose media, respectively, while sucrose and arabinose media achieved relatively higher production of 4.7 and 4.1 g/L, respectively. Deviation in pH of the fermentation broths from the optimum value of 4-5 generally had marked effect on biocellulose production with single sugars in feedstock. However, the final pH values recorded in the different sugar mixtures were approximately 3.3-3.4, which had lower effect on production hindrance. Analyzing profiles for sugars' concentrations and cell growth showed that large amount of the metabolized sugars were mainly utilized for bacterial cell growth and maintenance, rather than biocellulose production. This was clearly observed with single sugars of low production, while sugar consumption was rather utilized for biocellulose production with sugar mixtures. Results reported in this study demonstrate that agriculture residues might be used as potential feedstocks for the biocellulose nanofibres production. Not only this represents a renewable source of feedstock, but also might lead to major improvements in production if proper supplements and control were utilized in the fermentation process. PMID- 20358410 TI - Osteolysis in well-functioning fixed- and mobile-bearing TKAs in younger patients. AB - BACKGROUND: Periprosthetic osteolysis is an increasingly prevalent complication of TKA. To reduce the polyethylene wear and periprosthetic osteolysis, particularly in young patients, the design of the contemporary fixed-bearing TKAs has been modified and mobile-bearing TKAs have been introduced. QUESTIONS/PURPOSES: We asked whether the prevalence of osteolysis would be less in well-functioning mobile-bearing TKAs than in well-functioning contemporary fixed-bearing TKAs in young patients. PATIENTS AND METHODS: We compared 488 patients (894 knees) who received fixed-bearing knee prostheses with 445 patients (816 knees) who received mobile-bearing knee prostheses. There were 187 men and 301 women (mean age, 58.6 years; range, 33-65 years) in the fixed-bearing group and 167 men and 278 women (mean age, 55.7 years; range, 33-65 years) in the mobile-bearing group. The mean followup was 12.6 years (range, 10-17 years) in the fixed-bearing group and 12.9 years (range, 10-17 years) in the mobile-bearing group. RESULTS: The incidence of osteolysis was 1.6% (14 of 894 knees) in the fixed-bearing group and 2.2% (18 of 816 knees) in the mobile-bearing group at the final review. The mean postoperative Knee Society knee and function scores were 92.9 points and 83.5 points, respectively, in the fixed-bearing group and 90.7 points and 83.8 points, respectively, in the mobile-bearing group. The revision rates were 3.7% (33 of 894 knees) in the fixed-bearing group and 2.7% (22 of 816 knees) in the mobile-bearing group. CONCLUSIONS: We found the incidence of osteolysis, rate of revision, and implant survivorship were similar between fixed bearing and mobile-bearing TKAs in younger patients. PMID- 20358411 TI - A confirmed case of agranulocytosis after use of cocaine contaminated with levamisole. AB - More than 2 million Americans use cocaine each month (National Survey on Drug Use and Health, Department of Health and Human Services: Substance Abuse and Mental Health Services Administration (SAMHSA) & Office of Applied Studies (OAS), Rockville, MD 2007). Starting in early 2003, South American cocaine cartels began to add levamisole, a pharmaceutical agent, to bulk cocaine prior to shipment to the USA (Valentino and Fuentecilla 2005). A dramatic increase in the prevalence of levamisole in cocaine was noted in early 2008. By October, 30% of cocaine bricks analyzed by the United States Drug Enforcement Administration contained levamisole (Casale et al. 2008). Exposure to levamisole can cause agranulocytosis (Amery and Bruynseels 1992). We report the first confirmed case of agranulocytosis associated with consumption of levamisole-contaminated cocaine in the USA. A previously healthy adult male presented to the emergency department with 5 days of mouth pain. He admitted to chronic active ethanol and crack cocaine abuse. Laboratory studies revealed severe neutropenia, with an absolute neutrophil count of 19 cells/mm3 (normal = 1,500-8,000 cells/mm3). A urine screen for drugs of abuse was positive for cocaine metabolites and opiates. Evaluation of a peripheral blood smear showed leukopenia with severe absolute neutropenia. A bone marrow biopsy revealed recently injured bone marrow showing early recovery. While in the hospital, the patient had little spontaneous bone marrow recovery. He received granulocyte colony-stimulating factor with improvement in peripheral white blood cell counts. The residue in the patient's crack pipe contained 10% levamisole. Subsequently, levamisole was detected in the patient's urine. Levamisole-associated agranulocytosis should be considered in the diagnosis of patients who present with neutropenia and a history or evidence of cocaine use. PMID- 20358413 TI - Medical toxicology and public health: update on research and activities at the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry: introduction to activities at the radiation studies branch. PMID- 20358414 TI - A controlled clinical trial of a novel antivenom in patients envenomed by Bungarus multicinctus. AB - In northern Vietnam, a majority of severely envenomed patients are bitten by Bungarus multicinctus. Hitherto, these victims have received supportive care only. The aims of this study were to assess the possible efficacy and side effects of a new antivenom. This trial (ClinicalTrials.gov Identifier: NCT00811239) was performed during 2004-2006 at an ICU in Hanoi. For ethical reasons, the study was not randomized. All patients who fulfilled the inclusion criteria during 2004-2005 were prospectively enrolled, carefully recorded, and treated with optimal supportive therapy (control group). The patients who entered the study 2006 were treated with antivenom in addition to supportive care (antivenom group). The inclusion criteria were: envenomation by B. multicinctus, presence of systemic envenomation, and (during 2006) provision of written informed consent. Predefined endpoints were number of patients requiring mechanical ventilation, duration of mechanical ventilation, length of ICU stay, duration of muscle paralysis, and number of patients with ventilator-associated pneumonia. Eighty-one patients were included, 54 during 2004-2005 and 27 during 2006. Baseline characteristics were similar in the groups. The antivenom-group patients had a shorter duration of muscle paralysis of the limbs (p < 0.001), of the diaphragm (p < 0.001), and of ptosis (p < 0.001). The duration of mechanical ventilation and length of ICU stay were shorter in the antivenom group (p < 0.001). The rate of ventilator-associated pneumonia was lower in the antivenom group (p < 0.02). However, the relative number of patients requiring mechanical ventilation was not reduced in the antivenom group. The rate of adverse reactions to the antivenom was 7.4%. A favorable efficacy and acceptable safety of this antivenom were demonstrated. PMID- 20358415 TI - Alcohol levels do not accurately predict physical or mental impairment in ethanol tolerant subjects: relevance to emergency medicine and dram shop laws. AB - The human body and the central nervous system can develop tremendous tolerance to ethanol. Mental and physical dysfunctions from ethanol, in an alcohol-tolerant individual, do not consistently correlate with ethanol levels traditionally used to define intoxication, or even lethality, in a nontolerant subject. Attempting to relate observed signs of alcohol intoxication or impairment, or to evaluate sobriety, by quantifying blood alcohol levels can be misleading, if not impossible. We report a case demonstrating the disconnect between alcohol levels and generally assigned parameters of intoxication and impairment. In this case, an alcohol-tolerant man, with a serum ethanol level of 515 mg/dl, appeared neurologically intact and cognitively normal. This individual was without objective signs of impairment or intoxication by repeated evaluations by experienced emergency physicians. In alcohol-tolerant individuals, blood alcohol levels cannot always be predicted by and do not necessarily correlate with outward appearance, overt signs of intoxication, or physical examination. This phenomenon must be acknowledged when analyzing medical decision making in the emergency department or when evaluating the ability of bartenders and party hosts to identify intoxication in dram shop cases. PMID- 20358416 TI - Severe drug-induced liver injury associated with prolonged use of linezolid. AB - This study aims to describe a patient developing concomitant severe liver failure and lactic acidosis after long-term treatment with linezolid. A 55-year-old Caucasian woman developed concomitant severe liver failure and lactic acidosis after a treatment with linezolid for 50 days because of infected hip prosthesis. Other causes of liver failure and lactic acidosis were excluded by extensive diagnostic workup. A liver biopsy showed microvesicular steatosis. As linezolid toxicity was considered to be the cause of the lactic acidosis and the severe hepatic failure, the antibiotic was withdrawn. After 4 days of supportive therapy and hemodialysis, the serum lactate level returned within normal limits. The prothrombin time ratio and thrombocytes recovered within 2 weeks. Bilirubin levels normalized within 14 weeks. Since no other cause could be identified, liver injury was considered to be drug-related. Resolution of the hepatotoxicity occurred after discontinuation of linezolid, supportive treatment measures, and hemodialysis. Both lactic acidosis and microvesicular steatosis after the use of linezolid are related to mitochondrial dysfunction. The Council for International Organizations of Medical Sciences/Roussel Ucalf Causality Assessment Method scale revealed that the adverse drug event was probable. Prolonged exposure to linezolid may induce severe hepatotoxicity. Clinicians should be aware of this possible adverse effect especially in case of long-term treatment. PMID- 20358417 TI - Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. AB - INTRODUCTION: Cathinone is a pharmacologically active alkaloid that can be extracted from the leaves of the khat plant (Catha edulis). There are synthetic derivatives of cathinone entering the recreational drug market, including mephedrone (4-methylmethcathinone, 4-MMC). There are discrepancies in the legal status of both the khat plant and its extracted alkaloids between the UK and the USA. CASE REPORT: A 22-year-old man purchased 4 g of mephedrone powder over the Internet from a chemical supplier based in China. He initially ingested 200 mg of the mephedrone orally, with no perceived clinical effects, and thereafter injected the remaining 3.8 g intramuscularly into his thighs. Shortly after the injection, he developed palpitations, "blurred tunnel vision," chest pressure, and sweating and felt generally unwell; he presented to hospital with continuing features of sympathomimetic toxicity. His symptoms settled over the next 4 h after a single dose of oral lorazepam. Qualitative analysis of the urine and serum sample was undertaken using gas chromatography with mass spectrometric (GC/MS) detection, both positive for the presence of 4-methylmethcathinone. Quantitative analysis of the serum sample was undertaken by liquid chromatography with tandem mass spectrometric detection; the estimated mephedrone concentration was 0.15 mg/l. Routine toxicological analysis of the serum and urine specimens using a broad GC/MS toxicology screen did not detect any other drugs or alcohol. DISCUSSION: This is the first case of isolated 4-MMC toxicity, with confirmatory analytical findings. It is important that clinical toxicologists and emergency physicians work together to ensure a better understanding of the toxicity of novel/emerging drugs such as 4-MMC. PMID- 20358418 TI - A retrospective review of supratherapeutic modafinil exposures. AB - Modafinil is a non-amphetamine wakefulness-promoting agent used for the treatment of various sleep disorders characterized by excessive daytime sleepiness. There is little information in the medical literature with respect to supratherapeutic doses of this medication. We performed a retrospective review of the California Poison Control System database for all cases of single-substance ingestion of modafinil with follow-up to a known outcome for the time period 1998-2008. Data collected included age, gender, dose ingested, clinical effects, and medical outcome. There were a total of 87 patients, 53 (61%) of which were female. Patient ages ranged from 1.25 to 72 years with a mean of 30 years; 17 (20%) patients were aged 6 years or less. Thirty-three (38%) were intentional overdoses. Most commonly reported effects were tachycardia (n=23), agitation (n=14), anxiety (n=11), headache (n=8), hypertension (n=6), dystonia/tremor (n=6), and dizziness (n=5). Forty-nine patients (56%) were managed at home, and 38 (44%) were managed in a healthcare setting. Therapies administered included activated charcoal (n=8), benzodiazepines (n=7), antihistamines (n=2), intravenous fluids (n=2), haloperidol (n=2), and beta-blockers (n=1). Effects were classified as none (n=22), minor (n=54), and moderate (n=11). No major effects and no deaths occurred. Effects of modafinil overdose appear to be mild in most cases, with tachycardia and CNS symptoms predominating. Clinically significant effects requiring treatment occurred in a small number of patients. PMID- 20358419 TI - In vivo factors influencing tumour M2-pyruvate kinase level in human pancreatic cancer cell lines. AB - In tumour cells, the tetramer/dimer ratio of the pyruvate kinase isoenzyme type M2 (M2-PK) determines whether glucose carbons are degraded to lactate with production of energy (tetrameric form) or are channelled into synthetic processes (dimeric form). The influence of different tumour microenvironment conditions on the tetramer/dimer ratio of M2-PK and cell doublings were investigated in a non metastatic and metastatic pancreatic cancer cell line. The metastatic Colo357 cells contained about fourfold more M2-PK protein and about 3.5-fold more dimeric M2-PK than the non-metastatic Panc-1 cells. In Colo357 cells hypoxia, glucose starvation as well as acidification induced an increase of the dimeric form of M2 PK, whereas in Panc-1 cells no effect on M2-PK was observed. Under hypoxia in Colo357 cells, the dimerization and inactivation of M2-PK results in an inhibition of cell proliferation, whereas under glucose starvation and acidification the dimerization of M2-PK allowed further cell doublings. M2-PK expression and the quaternary structure of M2-PK are influenced by the tumour metastatic potential. The quaternary structure of M2-PK may be differently affected by hypoxia, glucose starvation and acidification with severe consequences on cell doublings. PMID- 20358420 TI - Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF. AB - Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of (125)I-labeled EGF. The anti-EGFR Affibody molecule (Z(EGFR:955))(2) was then assessed as a blocking agent of (111)In-labeled EGF in a dual isotope study (50, 100, and 200 microg, preadministered 30 or 60 min before (111)In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased (125)I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 microg (Z(EGFR:955))(2) as a blocking agent 30 min before the (111)In-EGF decreased the uptake of (111)In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (Z(EGFR:955))(2) shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging. PMID- 20358421 TI - Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression. AB - Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors. PMID- 20358422 TI - Serum micronutrient and antioxidant levels at baseline and the natural history of men with localised prostate cancer on active surveillance. AB - The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or=4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml( 1) year(-1). Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer. PMID- 20358423 TI - Antibody array-based technologies for cancer protein profiling and functional proteomic analyses using serum and tissue specimens. AB - In the context of other proteomic technologies, targeted antibody arrays are strongly contributing for protein profiling and functional proteomics analyses in serum specimens. Protein-protein interactions, post-translational modifications, and interaction between protein and DNA or RNA can all shift the activity of a protein from what would have been predicted by its level of transcription. Functional proteomics studies the interaction of proteins within their cellular environment to determine how a given protein accomplishes its specific cellular task. Accordingly, the promise of protein profiling and functional proteomics is that by chronicling the function of aberrant or over-expressed proteins, it will be possible to characterize the mechanism of the disease-sustaining proteins. The further understanding of the disease networks will eventually lead to targeted cancer therapy and specific biomarkers for diagnosis, prognosis or therapeutic response prediction based on disease specific proteins. This review describes how such strategies reported to date in serum specimens may assist in characterizing tumor biology, and for the diagnosis, surveillance, prognosis, and potentially for predictive and therapeutic purposes for patients affected with solid and hematological neoplasias. PMID- 20358424 TI - HE4: a new potential early biomarker for the recurrence of ovarian cancer. AB - Human epididymis protein 4 (HE4) has recently been described as a new marker for the early diagnosis of ovarian cancer (OC). The objective of this study was to evaluate (a) the expression of HE4 vs. OC mucin CA125 in 32 patients with OC compared to 163 patients with other malignant or benign pathologies (b) HE4 as indicator of the recurrence of the disease in eight patients followed-up for 20 months after OC diagnosis. Serum HE4 and CA 125 levels were determined by ELISA and IRMA, respectively. At diagnosis, the patients with OC demonstrated high levels of both biomarkers with 96.9% sensitivity for HE4 and 85.7% for CA125. In the other pathologies there was 3.7% positivity for HE4 and 21.0% for CA125. The follow-up study showed an increase of HE4 5-8 months before CA125 increment in five of the eight patients, this early expression being strictly associated to a relapse of the disease. In conclusion, this study showed that HE4, compared to CA125, potentially is a better marker for the diagnosis of OC and could be an important early indicator of the recurrence of the disease. PMID- 20358425 TI - Brain-derived neurotrophic factor induces proliferation, migration, and VEGF secretion in human multiple myeloma cells via activation of MEK-ERK and PI3K/AKT signaling. AB - This study investigated the signaling pathways involved in the different biological effects of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM). The effects of BDNF on proliferation of MM cell lines and primary myeloma cells were examined by [(3)H]thymidine incorporation assay. The effects of BDNF on MM cells migration were studied by transwell migration assay. Stimulation by BDNF of vascular endothelial growth factor (VEGF) production was analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. The signal-transduction pathways that are activated in response to BDNF were determined by Western blots. VEGF is induced by BDNF in a dose-dependent manner in MM cells. Stimulation of MM cells with BDNF led to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the MEK extracellular signal-regulated protein kinase pathways. Using specific signal transduction inhibitors, we demonstrated that MEK is required for BDNF-induced proliferation, whereas activation of PI3K is required for BDNF-stimulated migration and VEGF production. BDNF affects different cell signaling pathways mediating growth, migration, and VEGF secretion in MM cells. Our observations provided the framework for novel therapeutic strategies targeting BDNF signaling cascades in MM. PMID- 20358426 TI - Initial formation of IGROV1 ovarian cancer multicellular aggregates involves vitronectin. AB - Ovarian cancer progression is frequently associated with the development of malignant ascites. Multicellular aggregates of carcinoma cells (spheroids) found within ascites are thought to be able to promote peritoneal carcinomatosis. We have previously demonstrated the involvement of the vitronectin/alphav integrin adhesive system in the dissemination of ovarian cancer cells and continue to investigate the influence of these molecules by studying their role(s) in spheroid behavior. The aim of this study was to generate ovarian cancer multicellular aggregates and to focus on the role of vitronectin and alphav integrins in their initiation. IGROV1 cancer cells cultured in the absence of adhesive substratum formed multicellular aggregates comparable to spheroids. After 21 days, a fraction of the cells within clusters remained viable and proliferated recurrently. Within the multicellular aggregates, vitronectin and alphav integrins were co-localized at intercellular sites, suggesting their involvement in cell-cell interactions. Initial formation of IGROV1 aggregates was inhibited using anti-vitronectin and anti-alphav integrin blocking antibodies or the cyclic peptide cRGDfV. Vitronectin expression persisted during cluster disaggregation on fibronectin. These results demonstrate the ability of IGROV1 cells to generate multicellular aggregates and point to a contributory role for the vitronectin/alphav integrin system in the initial step of this process. These events could represent a prerequisite for further dissemination. PMID- 20358427 TI - Effect of cetuximab treatment in squamous cell carcinomas. AB - The purpose of this study was to assess the effects of the monoclonal antibody cetuximab in a panel of cultured squamous cell carcinoma cell lines. This antibody, targeting the epidermal growth factor receptor (EGFR), is emerging as a promising agent for treatment of several cancers. As this antibody comes into clinical use, the identification of predictive markers of therapeutic benefit remains a pressing issue. Cells were first characterized according to EGFR expression, cell doubling time, and BRAF and K-ras mutations. The effects of cetuximab on cell-cycle distribution, proliferation, as well as cell growth rate were then evaluated. Cetuximab decreased cell proliferation in three out of four cell lines in a time-dependent manner, and all cell lines were found to exhibit wild type K-ras and BRAF genes. A possible correlation between EGFR expression and cetuximab effect on growth inhibition rate was observed, whereas reduction of cell doubling time seemed to be more dependent on initial growth rate. In addition, other factors may further influence the long-term treatment response of cetuximab. Moreover, the time-dependent manner of cetuximab response demonstrates the importance of long-term measurements for this substance. PMID- 20358428 TI - From dispositional affect to academic goal attainment: the mediating role of coping. AB - The purpose of this research was to examine a mediation model in which coping was hypothesized to mediate the relationship between positive and negative dispositional affect and academic goal attainment. At Time 1, a sample of 217 undergraduate students completed measures of dispositional affect and set a personal academic goal. At Time 2, 4 weeks later, they completed a follow-up questionnaire assessing their coping strategies and degree of goal attainment. Results from structural equation modeling revealed that task-oriented coping significantly mediated the relationship between dispositional positive affect and goal attainment. Results also supported disengagement-oriented coping as a mediator in the relationship between dispositional negative affect and goal attainment. These findings highlight the role of coping as an important process in the relationship between dispositional affect and goal attainment. PMID- 20358429 TI - Bacterial attachment on optical fibre surfaces. AB - Optical fibres have received considerable attention as high-density sensor arrays suitable for both in vitro and in vivo measurements of biomolecules and biological processes in living organisms and/or nano-environments. The fibre surface was chemically modified by exposure to a selective etchant that preferentially erodes the fibre cores relative to the surrounding cladding material, thus producing a regular pattern of cylindrical wells of approximately 2.5 mum in diameter and 2.5 mum deep. The surface hydrophobicity of the etched and non-etched optical fibres was analysed using the sessile pico-drop method. The surface topography was characterised by atomic force microscopy (AFM), while the surface chemistry was probed by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Six taxonomically different bacterial strains showed a consistent preference for attachment to the nano-scale smoother (R(q) = 273 nm), non-etched fibre surfaces (water contact angle, theta = 106 degrees +/- 4 degrees). In comparison, the surfaces of the etched optical fibres (water contact angle, theta = 96 degrees +/- 10 degrees) were not found to be amenable to bacterial attachment. Bacterial attachment on the non-etched optical fibre substrata varied among different strains. PMID- 20358430 TI - Con un pie en dos islas: cultural bridges that inform sexual and reproductive health in the Dominican Republic and New York. AB - Immigrants from the Dominican Republic have grown in number and currently make up a substantial portion of New York City's population. In order to better understand the cultural context of Dominican women's sexual and reproductive health attitudes and practices, focus groups were conducted with Dominican women living in New York City as well as with women living in the Dominican Republic. Analysis found that women in the USA had more economic independence and a greater sense of freedom in regards to sexuality than women in the Dominican Republic. However, those in New York City also hoped to maintain their cultural identity in many ways. Women associated the prevalence of gender-based violence with male unemployment and alcohol abuse. Women in both locales reported limited condom use and saw contraception as a woman's responsibility. Many barriers to using the healthcare system were identified and, in many cases, there exists a preference for herbal treatments and folk remedies. This study provided many important insights that have the potential to increase the quality of sexual and reproductive health care for Dominican women. PMID- 20358431 TI - Further discussion on the design and analysis of thorough QTc clinical trials: guest editors' notes. PMID- 20358432 TI - Statistical characteristics of moxifloxacin-induced QTc effect. AB - Moxifloxacin has been the most commonly used positive control in "thorough" QTc (TQT) studies. In a TQT study, the assay sensitivity is often considered to be established if the baseline corrected mean difference in QTc between moxifloxacin and placebo is greater than 5 ms in common practice at one or more prespecified time points and the observed moxifloxacin induced QTc effect over time follows the proper pharmacokinetics profile. To better understand the statistical characteristics of moxifloxacin-induced QTc prolongation and to provide guidance for future studies, 20 TQT studies that involved moxifloxacin have been evaluated. We study the QTc profile of the baseline adjusted mean difference in QTc between moxifloxacin and placebo over time. Zhang (2008) proposed that the moxifloxacin induced QTc effect can be evaluated between 1 and 4 h after a single dose (400 mg) administration near the time (T(max)) of peak concentration instead of all time points (typically 9-12 time points) at which QT was measured for the study drug evaluation. After evaluating 20 TQT studies, we confirm that the maximum moxifloxacin effect occurs in the time window between 1 and 4 h post dose. We also investigate the variability of the data as well as correlations between time points and between regimens. These findings and results can be used as a reference for future studies. PMID- 20358433 TI - A nonparametric approach to QT interval correction for heart rate. AB - We propose to use generalized additive models to fit the relationship between QT interval and RR (RR = 60/heart rate), and develop two new methods for correcting the QT for heart rate: the linear additive model and log-transformed linear additive model. The proposed methods are compared with six commonly used parametric models that were used in four clinical trial data sets and a simulated data set. The results show that the linear additive models provide the best fit for the vast majority of individual QT-RR profiles. Moreover, the QT correction formula derived from the linear additive model outperforms other correction methods. PMID- 20358434 TI - A Bayesian measurement error approach to QT interval correction and prolongation. AB - Assessment of QT interval prolongation is an integral part of clinical studies in drug development because a prolonged QT interval can cause sudden cardiac death. Traditionally a linear or non-linear regression method is applied to estimate subject- or group-specific heart rate corrected QT intervals (QTc) on which comparisons are based among treatment groups. These regression models rely on a fundamental assumption that the predictor variable (RR interval) is measured without error. However, the fact is that both QT and RR intervals measured in electrocardiogram (ECG) are subject to not only measurement error, but also fluctuation that is caused by physiological and biological factors. Hence the assumption in the regression models is most likely violated. In this paper we propose a Bayesian hierarchical measurement error model to evaluate QTc interval and prolongation. The proposed approach is illustrated using a real data set. Simulation studies show that our proposed Bayesian measurement error approach outperforms the current most commonly used frequentist methods. PMID- 20358435 TI - Statistical characterization of QT prolongation. AB - The appropriate assessment of QT prolongation remains controversial. We suggest that before the relative merits of various methods can be evaluated, we must state what we assume an assessment of QT prolongation should be about. As a general framework for the assessment of QT prolongation we propose that an assessment of "absolute" or "uncorrected" QT prolongation is properly carried out through a between-treatment (active versus placebo) comparison of the marginal distributions of QT data; an assessment of "heart rate corrected" QT prolongation is carried out through a between-treatment comparison of the conditional distributions of QT data (conditional on RR interval or heart rate). Under this general framework, conditional QT prolongation is, in general, a function of RR interval, and we discuss three possible summary characteristics for that function. We show how current procedures for the assessment of QT prolongation relate to the general approach (that is, to between-treatment contrasts of the marginal and conditional expectation of the QT interval), and to each other. It transpires that only the so-called "one-step procedure" can provide a complete characterization of conditional QT prolongation. We show that the "two-step procedure" with data-driven correction provides an unbiased estimate of expected conditional QT prolongation, which may, from a clinical point of view, be a more satisfactory characteristic than the conventional characteristic, QT prolongation at the reference RR interval. We strongly suggest that two-step procedures with fixed correction be abandoned in the analysis of thorough QT/QTc studies: Fixed correction is either redundant (when a drug has no effect on average RR interval), or systematically biased (when a drug does affect average RR interval). PMID- 20358436 TI - Sample size calculation for thorough QT/QTc study considering various factors related to multiple time points. AB - The sample size requirement in a thorough QT/QTc study is discussed under a balanced parallel or crossover study design. First, we explore the impacts of various factors on the study power, including the mean effect profile across time and correlation among time points. Then we estimate the variability parameters needed based on multiple historical studies. Different baseline usage is illustrated to have a significant impact on the analysis variability in the parallel studies. Finally, the sample size calculations and recommendations are given for demonstrating a "negative" drug effect and the study assay sensitivity, respectively. PMID- 20358437 TI - Sample size and power estimation in "thorough" QT/QTc studies with parallel group design. AB - We developed analytical results for computing the power in a thorough QT/QTc study with a four-group parallel design in which the treatments are placebo, positive control, supratherapeutic dose of investigational drug, and therapeutic dose of investigational drug. An assessment of non-inferiority of the supratherapeutic dose to placebo is performed by the intersection-union test within the framework of a linear mixed effects analysis with baseline covariate. The power estimates obtained using analytical results and from the simulation study were presented and they are quite close and hence the analytical results could be used for computing power and sample size in the planning stage of a thorough QT/QTc study. PMID- 20358438 TI - Sample size calculations for crossover thorough QT studies: satisfaction of regulatory threshold and assay sensitivity. AB - The cost for conducting a "thorough QT/QTc study" is substantial and an unsuccessful outcome of the study can be detrimental to the safety profile of the drug, so sample size calculations play a very important role in ensuring adequate power for a thorough QT study. Current literature offers some help in designing such studies, but these methods have limitations and mostly apply only in the context of linear mixed models with compound symmetry covariance structure. It is not evident that such models can satisfactorily be employed to represent all kinds of QTc data, and the existing literature inadequately addresses whether there is a change in sample size and power for more general covariance structures for the linear mixed models. We assess the use of some of the existing methods to design a thorough QT study through data arising from a GlaxoSmithKline (GSK) conducted thorough QT study, and explore newer models for sample size calculation. We also provide a new method to calculate the sample size required to detect assay sensitivity with adequate power. PMID- 20358439 TI - Multiple comparisons of repeated measured response: issues of assessment of prolongation of QT interval in thorough QT trials. AB - The primary objective of a thorough QT clinical trial is to demonstrate the lack of QT prolongation induced by the test treatment. The ICH E14 guidance defined drug-induced prolongation of QT interval as evidenced by an upper bound of the 95% one-sided confidence interval around the mean effect on QTc of 10 ms. Furthermore, it defined a negative thorough QT/QTc study as one in which the upper bound of the 95% one-sided confidence interval for the largest time-matched mean effect of the drug on the QTc interval excludes 10 ms. Conventionally, this objective is tested with the intersection-union test by testing the mean difference between the test treatment and placebo of QTc changes from baseline at each of the matched time points. The multiple-comparison nature of the test leads to higher false positive rate when comparisons are made repeatedly at multiple time points. Many approaches have been proposed in the last 5 years in order to improve the efficiency of the test. In this article, we survey and discuss some of the approaches. PMID- 20358440 TI - Exposure-response modeling approach for assessing QT effect in "thorough" QT/QTc studies. AB - We assess the QT effect using an exposure-response model in a "thorough QT/QTc study" with a four-period crossover design in which the treatments are placebo, positive control, higher dose of investigational drug, and therapeutic dose of investigational drug. In the study, QTc interval values and the drug concentrations are obtained for several specified times during treatment. This approach to the assessment of non-inferiority of the higher dose to placebo is an alternative strategy suggested in ICH-E14 guideline (Section 2.2.5) to the intersection-union test. PMID- 20358441 TI - A comparison of several methods for analyzing data from thorough QT studies. AB - Currently, the intersection-union test (IUT) is the standard method of analysis of the data from a thorough QT (TQT) study. In this current work, we compared the methods proposed in three recent publications (Boos et al., 2007; Cheng et al., 2008; Eaton et al., 2006) to IUT using a simulation study. The methods proposed by Cheng and Eaton did not produce a considerable improvement over IUT in the power and size of the test. The power of the Boos et al. method was a substantial improvement over IUT, but the size of the test was found to be greater than 5%. PMID- 20358442 TI - Statistical consideration in testing for assay sensitivity in a "thorough" QT study. AB - The current guidelines, ICH E14, for the evaluation of non-antiarrhythmic compounds recommends a "thorough" QT study (TQT) to be conducted during clinical development. Typically the treatment arms in the TQT study should include study drug at therapeutic and supra-therapeutic doses, placebo and a positive control such as Moxifloxacin (Avelox). The current hypothesis for assay sensitivity involves testing at pre-selected time points, where electrocardiograms (ECG) are obtained, if the mean baseline adjusted differences between positive control and placebo are greater than 5 ms. Since multiple time points are tested, the overall type I error rate should be adjusted using an appropriate multiple comparison procedure. In this article, we consider some recently proposed tests (Zhang, 2008) and explore the use of some standard global test procedures such as O'Brien's ordinary least squares (OLS) and Lauter's standardized sum (SS) tests for testing sensitivity of positive control. The powers of several test procedures are evaluated using simulation. The simulation shows that Zhang's method performs quite well in general but the OLS and SS tests have higher power when the coefficient of variations of QTc intervals have high heterogeneity. PMID- 20358443 TI - Multiple comparisons of repeatedly measured response: issues of validation testing in thorough QT/QTc clinical trials. AB - In order to validate the results of a thorough QT/QTc clinical trial, ICH E14 recommended that a concurrent positive control treatment be included in the trial. Zhang (2008) recommended that the study results are validated if the positive control establishes assay sensitivity, i.e., has an effect on the mean QT/QTc interval of 5 ms or more. Zhang (2008) and Tsong et al. (2008) discussed the intersection-union test approach and an alternative global average test approach for testing assay sensitivity during the validation process. In this article, we further discuss the multiple comparison issues of the repeatedly measured QT difference between positive control treatment and placebo in the validation test. We describe and discuss several approaches for type I error rate adjustment that are applicable to the situation. PMID- 20358444 TI - Use of the average baseline versus the time-matched baseline in parallel group thorough QT/QTc studies. AB - Using historical studies, we compared the impact of using the average baseline or time-matched baseline on diurnal effect correction, treatment effect estimation, and analysis of variance/covariance (ANOVA/ANCOVA) efficiency in a parallel thorough QT/QTc (TQT) study. Under a multivariate normal distribution assumption, we derived conditions for achieving unbiasness and better efficiency when using the average baseline, and confirmed these conditions using historical TQT studies. Furthermore, simulations were conducted under the randomized trial with and without observed imbalanced baseline settings. We conclude that the analyses using average baseline yield better efficiency and unbiased or less biased results under our TQT study conditions. PMID- 20358445 TI - Revisit the combination validation test of Tsong et al. for thorough QT/QTc clinical trials. PMID- 20358447 TI - Response to letter to the editor: Statistical issues of QT prolongation assessment based on linear concentration modeling by Yi Tsong et al. PMID- 20358453 TI - On the inconsistencies related to prediction of flow into an enclosing hood obstructed by a worker. AB - The recirculating flow structures formed in the wake of a worker standing in front of an enclosing fume hood were numerically investigated. Two- and three dimensional, unsteady, laminar/turbulent computations were performed for a Reynolds number (Re) range of 1.0 x 10(3)-1.0 x 10(5). The standard k-epsilon, Renormalization group (RNG) k-epsilon, and Shear Stress Transport (SST) k-omega models were used in Unsteady Reynolds Averaged Navier-Stokes (URANS) computations, and the results were compared with each other and also with the previous predictions reported in the literature. Numerical issues regarding the grid convergence and the inadequacies of turbulence models that may come into play at low Reynolds numbers were addressed. On the whole, SST k-omega model was found to be promising for qualitatively accurate prediction of both steady and unsteady recirculatory flow patterns in the wake of the worker. On the other hand, the standard and RNG k-epsilon models failed in prediction of anticipated unsteadiness at low Reynolds numbers. In a more realistic three-dimensional simulation with SST k-omega model, the anticipated unsteady and recirculating flow field in the wake of the worker was captured. Present results seem to qualitatively agree with the deductions made from experimental analyses in the literature while conflicting with some aspects of the previously reported numerical results. The apparent inconsistencies observed between the current results and those published in the literature were elucidated. PMID- 20358452 TI - Diagnosis of Alzheimer's disease using neuropsychological testing improved by multivariate analyses. AB - Neuropsychological assessment aids in the diagnosis of Alzheimer's disease (AD) by objectively establishing cognitive impairment from standardized tests. We present new criteria for diagnosis that use weighted combined scores from multiple tests. Our method employs two multivariate analyses: principal components analysis (PCA) and discriminant analysis. PCA (N = 216 participants) created more interpretable cognitive dimensions by resolving 49 test measures in our neuropsychological battery to 13 component scores for each participant. The component scores were used to build discriminant functions that classified each participant as either an early-stage AD (N = 55) or normal elderly (N = 78). Our discriminant function performed with high accuracy, sensitivity, and specificity (nearly all >90%) in the development, a cross-validation, and a new-subjects validation. When contrasted to two different traditional empirical methods for diagnosis (using cutscores and defining AD as falling below 5% on two or more test domains), our results suggested that the multivariate method was superior in classification (approximately 20% more accurate). PMID- 20358454 TI - Annual Review of Sex Research. PMID- 20358455 TI - Elucidating women's (hetero)sexual desire: definitional challenges and content expansion. AB - The literature on women's sexual desire is reviewed with an emphasis on definitional challenges, an assessment of the empirical basis for the distinction between spontaneous and responsive desire, a reconsideration of the extent to which women's sexual desire is relational in nature, and an exploration of the incentive value of sex for women as a factor partially independent from the experience of sexual desire. Nine recommendations are made regarding research and diagnostic directions. The article concludes with an appeal for the inclusion of eroticism in research and clinical work on sexual desire. PMID- 20358456 TI - Heterosexual anal sexuality and anal sex behaviors: a review. AB - Little research addresses the role of anal sexuality and anal sexual behaviors as a widely practiced but relatively less frequent element of a heterosexual sexual repertoire. However, the importance of anal sex in sexual health is increasingly well-defined by epidemiological and clinical studies. This article reviews existing data on a range of heterosexual anal sex practices and provides conceptual and methodological recommendations for new research. PMID- 20358457 TI - First heterosexual intercourse in the United kingdom: a review of the literature. AB - First sexual intercourse is an event of immense social and personal significance, which also has major health implications. However, there has been no recent review of the literature in the United Kingdom specifically relating to this event. This review addresses this gap, examining the timing, circumstances, and consequences of first heterosexual intercourse. Studies were identified by electronic search, as well as through contact with experts in the field. Academic literature published from 1960 and pertaining to the UK context was included. A dominant focus of the literature is on the timing of the event, which shows that the age at which young people become sexually active has fallen in recent decades. In addition, much of the literature is concerned with the risk of adverse outcomes, and a young age at first sex is often associated with more negative consequences. There is evidence to suggest that age may not be the most useful criterion for judging optimal timing for first having sex. It is proposed that a more promising concept in relation to first sexual intercourse is that of sexual readiness. PMID- 20358458 TI - Chronic disease and sexuality: a generic conceptual framework. AB - Although sexual dysfunctions are frequently comorbid with many chronic diseases and their treatments, until recently, these dysfunctions have been neglected in both research and clinical practice. Fortunately, sexual functioning in the context of chronic disease has now begun to receive more scientific attention. Studies in the field are, however, quite diverse in terms of topics and methodology, not only making comparisons across studies on a single disease difficult, but also making comparisons across different diseases impossible. In an attempt to inspire researchers, this article presents a "generic" conceptual framework regarding the impact of chronic diseases (and their treatments) on sexual function. The major goals of this conceptual framework are to provide an in-depth analysis of, and insight into, the process by which disease-related psychological and relational factors impact the sexual functioning and well-being of patients, their partners, and their relationships. Some of the associations within the conceptual framework have already been supported by the results of empirical studies on various diseases. This review ends with an overview of the limitations of previous research, proposes a research agenda for the field, and presents a research tool that may be helpful in developing new studies investigating the association between chronic diseases and sexuality. PMID- 20358459 TI - Human nonverbal courtship behavior--a brief historical review. AB - This article reviews research findings documenting the nature of nonverbal courtship behavior compiled through both observation and self-report methods. I briefly present the major theoretical perspectives guiding research methodologies used in the field and in the laboratory. Studies of verbal courtship, including those conducted via computer, via text messaging, or through personal advertisement, are not included in this review. The article ends by elucidating some key features of human nonverbal courtship behavior that have become apparent after scrutinizing these data. PMID- 20358460 TI - Diagnosis, assessment, and treatment of hypersexuality. AB - This article reviews the current evidence base for the diagnosis, assessment, and treatment of hypersexual conditions. Controversy concerning this diagnosis is discussed. Terminology and diagnostic criteria, as well as psychological, psychopharmacological, and other treatment approaches, are presented. PMID- 20358461 TI - Sexual dysfunction in women with diabetes mellitus. AB - Diabetes mellitus (DM) is an increasing health concern throughout the world. DM is categorized as either type 1 (DM-1) or type 2 (DM-2), where DM-1 represents a lack of insulin production, and DM-2 is characterized by a relative lack of insulin (i.e., decreased sensitivity to the effect of insulin). DM has long been considered a risk factor for sexual dysfunction in men and women, although the evidence in women is less clear. This review attempts to give an overview of female sexual dysfunction in women with DM. Although women with DM are at higher risk of developing sexual dysfunction than women without DM, there is great variability in results across studies, with the incidence of sexual dysfunction in women with DM generally linked less to organic factors and more to psychological factors, especially coexisting depression. This review hypothesizes several presumed causes for such variation in findings across studies and uses these explanations as the basis for a discussion of differences between men's and women's sexuality. PMID- 20358462 TI - Dance and sexuality: many moves. AB - This literature review of dance and sexual expression considers dance and religion, dance and sexuality as a source of power, manifestations of sexuality in Western theater art and social dance, plus ritual and non-Western social dance. Expressions of gender, sexual orientation, asexuality, ambiguity, and adult entertainment exotic dance are presented. Prominent concerns in the literature are the awareness, closeting, and denial of sexuality in dance; conflation of sexual expression and promiscuity of gender and sexuality, of nudity and sexuality, and of dancer intention and observer interpretation; and inspiration for infusing sexuality into dance. Numerous disciplines (American studies, anthropology, art history, comparative literature, criminology, cultural studies, communication, dance, drama, English, history, history of consciousness, journalism, law, performance studies, philosophy, planning, retail geography, psychology, social work, sociology, and theater arts) have explored dance and sexual expression, drawing upon the following concepts, which are not mutually exclusive: critical cultural theory, feminism, colonialism, Orientalism, postmodernism, poststructuralism, queer theory, and semiotics. Methods of inquiry include movement analysis, historical investigation, anthropological fieldwork, autoethnography, focus groups, surveys, and self-reflection or autobiographical narrative. Directions for future exploration are addressed. PMID- 20358463 TI - Paraphilias across cultures: contexts and controversies. AB - Cultures define and describe what is normal and what is deviant. These definitions of normality vary across cultures and are influenced by a number of factors, such as religion. Cultures have been described in various ways, including sex-positive where the sexual act itself is seen as important for pleasure, or sex-negative where the sexual act is seen only as for procreative purposes. The role and development of paraphilias across cultures is also variable, with cultures defining what is legal or illegal. Such differences make collection of epidemiological data and comparison across paraphilias problematic. This discussion suggests that characteristics of cultures may influence the rate of reporting paraphilias, as well as the rate of paraphilias themselves. Furthermore, with increased industrialization and urbanization, families will become more nuclear, with attitudes toward sex and paraphilias changing as well. This review also explores whether paraphilias can be seen as culture-bound syndromes, and recommends consideration of a number of conceptual issues regarding the diagnosis and prevalence of paraphilias as future cross-cultural studies on this topic are developed. PMID- 20358464 TI - Epidemiologic evidence on coffee and cancer. AB - Coffee consumption is a major and frequent dietary exposure in diverse cultures around the globe whose safety has been questioned. A substantial body of epidemiologic evidence, consisting of over 500 papers relating the consumption of coffee to cancer of various sites, has accumulated to date. Numerous individual, site-specific meta analyses have been undertaken at various times. However, there is no comprehensive, up-to-date overview of the entirety of the knowledge base. To address this need, this review summarized the findings of the meta analyses and recent papers on site-specific human cancers among coffee consumers. For hepatocellular and endometrial cancers, there appears to be a strong and consistent protective association; for colorectal cancer, the direction of association is borderline protective. There appears to be no association with breast, pancreatic, kidney, ovarian, prostate, or gastric cancer. Risk of bladder cancer appears to be associated with heavy coffee consumption in some populations and among men. The associations with childhood leukemia and mother's consumption of coffee were ambiguous-with some suggestion of risk at high levels of daily consumption. PMID- 20358465 TI - Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids. AB - The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority. PMID- 20358466 TI - Dairy products and prostate cancer risk. AB - Increased calcium intake from dairy products has been suggested as a risk factor for prostate cancer. We propose that the high dietary phosphate of dairy products may more readily explain this risk rather than the increased calcium. Several epidemiologic correlations have indicated an increased risk of prostate cancer with long-term, high intake of dairy products in male U.S. physicians and males in Sweden. This relation has been mechanistically associated with the higher dietary intake of calcium in dairy products. We propose, however, that the high dietary phosphate of dairy products affects much larger fluctuation in serum phosphate and may be a more likely source of prostate cancer risk from high dietary intake of dairy products. PMID- 20358467 TI - Common dietary patterns and risk of breast cancer: analysis from the United Kingdom Women's Cohort Study. AB - The relationship between diet and breast cancer is uncertain. We assessed the relationship of 4 common dietary patterns to the risk of breast cancer using the UK Women's Cohort Study (UKWCS). A total of 35,372 women aged between 35 to 69 yr were recruited from 1995 to 1998. The UKWCS was selected to have a wide range of dietary intakes; 28% were self-reported vegetarian. Diet was assessed at baseline by a 217-item food frequency questionnaire. Four dietary patterns were defined based on a hierarchy of consumption of fish and meat to reflect commonly consumed dietary patterns. Hazards ratios (HRs) were estimated using Cox regression adjusted for known confounders. Subjects were followed up for a mean of 9 yr, and 330 premenopausal and 453 postmenopausal women developed invasive breast cancer. In postmenopausal women, there was a strong inverse association between the fish eating dietary pattern 0.60 (95% CI = 0.38-0.96) but not for a vegetarian pattern 0.85 (95% CI = 0.58-1.25) compared to red meat eaters. There were no statistically significant associations with dietary pattern and risk of premenopausal breast cancer. A fish eating dietary pattern that excludes meat from the diet may confer some benefit with regard to risk of postmenopausal breast cancer. PMID- 20358468 TI - Fluid intake and colorectal cancer risk in the Netherlands Cohort Study. AB - Total fluid intake, specifically water intake, has been suggested to protect against colorectal cancer. We examined the association of total fluid intake with colorectal cancer endpoints and possible effect modification by fiber intake within the Netherlands Cohort Study (N = 120,852). We also investigated intake of specific beverages. After 13.3 yr, 1,443 male and 1,040 female colorectal cancer cases with complete baseline questionnaires were available for case-cohort analyses. Multivariate analyses showed no dose-response relationship of total fluid intake and intake of specific beverages with the risk of overall colorectal, proximal, and distal colon cancer. For rectal cancer risk in men, there was a nonsignificant positive trend for total fluid intake [> 1,500 vs. 6 vs. 5 points) patients were allocated to a group without (n = 160) or with symptoms suggestive of depression (n = 82). The study groups did not differ with respect to age, sex or place of residence. Univariate logistic regression analysis showed that independent predictors for the presence of symptoms suggestive of depression at 3 months after stroke were: low level of education, low income, greater severity of stroke, worse functional status, self-reported problems with daily living activities and need of help in daily living activities. More than 60% of patients with depressive symptoms limited their social contacts. Patients with depressive symptoms were unsatisfied with their relations with life partners and friends. CONCLUSIONS: Our study showed a complex aetiology of post-stroke depressive symptoms with an important role of socioeconomic factors. Depressive symptoms after stroke worsen existing health, social and economic problems, and cause social isolation of patients. PMID- 20358482 TI - Degenerative pontine lesions in patients with familial narcolepsy. AB - BACKGROUND AND PURPOSE: Narcolepsy is characterized by chronic excessive daytime sleepiness with episodic sleep attacks. There are several associated symptoms of narcolepsy: cataplexy (bilateral muscle weakness without loss of consciousness provoked by an emotional trigger, e.g. laughter), sleep paralysis and hypnagogic hypnopompic hallucinations. Most cases are sporadic; familial narcolepsy contributes to only 1-5% of all cases. While most cases of narcolepsy are idiopathic and are not associated with clinical or radiographic evidence of brain pathology, symptomatic or secondary narcolepsy may occur occasionally in association with lesions caused by tumours, demyelination or strokes of the diencephalon, midbrain, and pons. There are some examples of non-specific brainstem lesions found in magnetic resonance imaging (MRI) in patients with idiopathic narcolepsy. MATERIAL AND METHODS: The authors present eleven patients from a five-generation family with many members who suffer from episodic excessive daytime sleepiness. Narcolepsy was diagnosed in 9 patients. Sleepiness was frequently associated with cataplexy, hypnagogic-hypnopompic hallucinations and sleep paralysis. Improvement in their clinical state was observed during the treatment with modafinil. All probands had MRI of the brain, routine blood tests, EEG, polysomnography, examination of the level of hypocretin in cerebrospinal fluid and evaluation by means of Epworth and Stanford Sleepiness Scales. RESULTS: In 9 patients with narcolepsy, decreased thickness of the substantia nigra was found and in six of them degenerative lesions in the pontine substantia nigra were also noticed. CONCLUSIONS: The significance of these changes remains unclear. No data have been published until now concerning the presence of any brain lesions in patients with familial narcolepsy. PMID- 20358483 TI - Radiation therapy in paediatric gliomas: our institutional experience. AB - BACKGROUND AND PURPOSE: The aim of our retrospective study was to analyze the clinical outcome of paediatric glioma patients treated with radiation therapy (RT) in our institution. MATERIAL AND METHODS: We retrieved the case records of all children with gliomas (age < 18 years) who received RT in our department between 2004 and 2007. We analyzed the information regarding patients' demography, clinical details, treatment given, RT details, and survival. The event-free survival (EFS), the period from the date of completion of RT to the date of the event, i.e. death/recurrence, was calculated with respect to age, sex, location of tumour (brainstem vs. non-brainstem), histopathology (low grade vs. high grade), extent of surgical resection, dose and duration of RT, and use of chemotherapy. RESULTS: A total of 70 children with glioma received RT during the above-mentioned period. The 3-year EFS rate for all patients was 44% and the median EFS period was 18 months. The 3-year EFS in patients who underwent surgical decompression and no surgery was 58% and 25%, respectively (p < 0.05). Patients with brainstem lesions had statistically significantly lower 3-year EFS to non-brainstem gliomas (28% vs. 56%, p < 0.01). Chemotherapy use showed no statistically significant trend towards better survival. CONCLUSIONS: RT is an effective modality of treatment in paediatric glioma patients in our setup. Early use of RT in incompletely resected low-grade gliomas is worth revisit-ing. Results of chemotherapy in high-grade glioma and brainstem gliomas are encouraging. PMID- 20358484 TI - Evaluation of postural balance control in patients with multiple sclerosis - effect of different sensory conditions and arithmetic task execution. A pilot study. AB - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect of concomitant cognitive task execution and different sensory conditions on balance control in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Thirty-two subjects with MS and 30 healthy age- and sex-matched control subjects were included in the study. Balance Performance Oriented Mobility Assessment was performed in all subjects. Their spontaneous sway characteristics while standing with different sensory conditions and during execution of a simple arithmetic task were analysed. Mean sway in the coronary and sagittal plane, as well as sway velocity, were measured. RESULTS: The values of all evaluated variables obtained in all tests were significantly higher in the MS group than in controls. In the MS group, more pronounced progression of changes in response to increased difficulty of the test was also observed. Analysis of risk of falls in MS revealed a significant increase of sway velocity and mean sway in the mediolateral and anteroposterior plane in the majority of tests. CONCLUSIONS: Postural stability in patients with MS is significantly decreased in comparison with the control group in all evaluated conditions. Stability deficit is enhanced in response to more difficult conditions of evaluation. Increased risk of falls is related to the increased postural sway velocity and length of mean sway; this association is most pronounced in the coronary plane. PMID- 20358485 TI - [Are botulinum toxin type A preparations really the same medication? A comparison of three botulinum toxin A for variations in labelled neurological indications]. AB - Recently, the list of clinical applications of botulinum toxin type A (BTX-A) enlarged. This medication is used not only by neurologists, but also by medical rehabilitation specialists, urologists, proctologists, and migraine and aesthetic medicine specialists. Currently, there are three commercially available BTX-A preparations available: Botox, Dysport and Xeomin. They have similar mechanisms of action but their chemical formulation, clinical potency, migration and diffusion as well as safety profile seem to be different. This may result in problems of bioequivalence, not only clinical but also economic ones. The authors reviewed the available clinical and laboratory studies on neurological indications labelled in Poland. Each BTX-A formulation should be treated as a different medication and used cautiously according to the individual range of dosages established in clinical trials. PMID- 20358486 TI - [The role of cyclooxygenases in neurotoxicity of amyloid beta peptides in Alzheimer's disease]. AB - In the course of Alzheimer's disease (AD), chronic inflammation is initiated by amyloid beta (Ab) peptide aggregates that extensively participate in neurodegeneration. Epidemiological studies have shown that long-term use of non steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. NSAIDs are inhibitors of cyclooxygenases (COXs), enzymes involved in synthesis of eicosanoids, a major component of the inflammatory process. Recent studies have brought two new findings: 1) the toxic form of Ab is its intra- and extracellular oligomers, rather than aggregates; 2) COX-2 activation is an early event in AD, preceding plaque formation and microglia activation. This finding suggests that COX might participate in Ab toxicity in neurons in the early stage of AD independently of its role in the inflammatory reaction in glial cells in the advanced stage of AD. However, further studies on the role of COXs in the pathogenesis/pathomechanism of AD are needed. PMID- 20358487 TI - The role of the PTEN gene in malignant gliomas. AB - This article focuses on the latest data about the role of the gene for phosphatase and tensin homologue located on chromosome 10 (PTEN) in malignant gliomas. PTEN acts as a tumour suppressor gene and plays a critical role in cell cycle progression, angiogenesis, migration, invasions and stem cell regulation. Furthermore, there is an interaction with other tumour suppressor genes. We discuss the role of miRNAs in modulating PTEN expression and also PTEN's role in the nucleus. PMID- 20358488 TI - [Spontaneous third ventriculostomy in obstructive hydrocephalus with composed aetiology: a case report]. AB - Third ventriculostomy (TV) is the most common neuroendoscopic procedure for restoration of near physiological circulation of cerebrospinal fluid in obstructive hydrocephalus. Among 70 adults operated on using this technique, the authors encountered one case of spontaneous TV. Only a few case reports of spontaneous ventriculostomy revealed by ventriculography, flow-sensitive phase contrast cine magnetic resonance imaging (MRI) or at autopsy have been published. A 43-year-old woman with symptoms of hydrocephalus and signs of chronic obstructive hydrocephalus secondary to aqueductal stenosis on MRI was qualified for TV. Enlarged infundibulo-mammillary triangle with perforation was noted intraoperatively. During the postoperative course, the condition of the patient partially improved although radiological appearance remained unchanged. Three weeks later symptoms of hydrocephalus recurred and the patient underwent an infusion test which revealed increased cerebrospinal fluid outflow resistance. Implantation of a ventriculo-peritoneal shunt yielded stable improvement. Spontaneous TV should be taken into consideration during selection of patients for TV, especially in cases with chronic obstructive hydrocephalus. PMID- 20358489 TI - Giant schwannoma of the lumbar spine. A case report. AB - Giant "invasive" schwannomas of the spine occur occasionally, most frequently in the lumbar region. We present the case of a 46-year-old woman with giant "invasive" schwannoma of the lumbar spine, with a 12-year history of illness. The tu-mour originated in the vertebral canal and passed through the paraspinal muscles and retroperitoneal area to the abdominal cavity. The part of the tumour which was in the abdominal cavity was removed by means of laparotomy during the first operation. In the second one, the remaining part of the tumour was removed completely from the vertebral canal and retroperitoneal area through posterior lateral access. The spine was stabilized with metal implants. Histological examination revealed cellular schwannoma. During the follow-up the pain resolved while paresis of the right quadriceps muscle of the thigh was still present. Cellular schwannoma is a benign form of schwannoma, but it may cause a local recurrence if not removed completely. PMID- 20358490 TI - History of Polish neurology and neurosurgery. Samuel Goldflam. PMID- 20358492 TI - [Intensive care and infectiology--important elements of internal medicine]. PMID- 20358493 TI - [Life-threatening complications of Crohn's disease and ulcerative colitis: a systematic analysis of admissions to an ICU during 18 years]. AB - BACKGROUND AND OBJECTIVE: Despite numerous publications on the epidemiology of inflammatory bowel diseases (IBD) there is a lack of systematic investigations on live-threatening complications of IBD and their causes. This study evaluates risk factors, course and outcome in intensive-care patients which were related to complications of IBD. PATIENTS AND METHODS: Among 6071 admissions to the intensive-care unit (ICU) of a gastroenterological department (university hospital with IBD-outpatient unit) between 1.1.1991 and 31.1.2008 36 ICU admissions of 28 patients with IBD were documented and prospectively analysed from 1996 onwards, using a structured questionnaire on causes for ICU admission as well as risk factors regarding death, organ failure and length of ICU stay. RESULTS: ICU admissions of IBD patients mainly resulted from three causes: complications specific to IBD (44 %), including acute flare-up, perforation and electrolyte imbalance, septic complications (22 %) and thromboembolic complications (17 %). Five patients died, all from septic complications related to immunosuppression including candida sepsis, varicella pneumonia during treatment with infliximab, and pneumocystis pneumonia related to treatment with azathioprine. The most important risk factors according to uni- and multivariate analyses were old age on ICU-admission and first diagnosis of IBD, previous surgery related to IBD and Crohn's disease. CONCLUSIONS: Complications of both IBD and immunosuppressive therapy may be live-threatening in patients with IBD. Better characterization of patients with a high probability of improved outcome by immunosuppressive and/or antibody-therapy seems to be preferable to noncritical early use of these drugs. PMID- 20358494 TI - [Leptospirosis (Weil's disease) in Augsburg]. AB - HISTORY: Three unrelated patients presented within three months at the Central Hospital of Augsburg, Southern Germany, with jaundice of initially unknown etiology. Patient (Pt.) 1, a 51-year old man was admitted with a history of nausea, vomiting, diarrhea, jaundice and anuria. Pt. 2 was a 58-year-old man who had fever and shivering, and had developed jaundice after a fishing-trip to Canada. Pt. 3 was a 66-year-old woman who presented at the Emergency Unit with recently developed jaundice and pain in the right lateral epigastric area. INVESTIGATIONS: Laboratory results showed elevated levels for bilirubin, CK, BUN, creatinine and low thrombocytes in patients 1 and 2. An elevated lipase level was found in Pt 1, while Pt 3 had an elevated bilirubin and thrombocytopenia. In Pt 1 and 2 active leptospirosis was diagnosed by serological tests. The third patient showed a subsided leptospirosis, the jaundice having been due to a histologically confirmed drug-associated hepatitis. TREATMENT AND COURSE: Patients 1 and 2, who had active disease, showed the full-blown clinical picture of Weil's disease with jaundice, renal failure and thrombocytopenia. After administration of penicillin G and a third generation cephalosporin (ceftriaxone), respectively, all symptoms disappeared. The 66-year-old woman (Pt 3) developed pneumonia and died of multiple organ failure. CONCLUSION: Leptospirosis is an important differential diagnosis in patients with recent onset of jaundice and acute renal failure. A detailed history may offer the crucial hint and serological tests provide proof. The clinical outcome mainly depends on starting antimicrobial therapy with penicillin G or a third generation cephalosporin as soon as practicable. PMID- 20358495 TI - [Unclear cause of ileus]. PMID- 20358496 TI - [Interdisciplinary emergencies in rheumatic diseases]. AB - Rheumatic disease can affect and severely damage vital organs and thus cause acute emergencies and life-threatening complications. As systemic diseases they can cause any presenting complaint commonly encountered in emergency medicine. Because of their relative rarity in general practice, a high level of vigilance is required in order to recognize an emergency caused by an underlying rheumatic disease in individual cases. The most important rheumatological emergencies comprise septic arthritis, gout, atlantoaxial subluxation, renal crisis and digital ulcers in systemic sclerosis, amaurosis fugax in giant cell arteritis, the catastrophic anti-phospholipid antibody syndrome and the pulmonary-renal syndrome. This article provides an overview over these rheumatological emergencies in order to aid recognition of these entities in individual cases and to thus facilitate immediate and adequate treatment, which is of vital importance for affected patients. PMID- 20358497 TI - [Clostridium difficile infection]. PMID- 20358498 TI - [Tight glucose control in intensive care patients--pro]. PMID- 20358499 TI - [Tight glucose control in intensive care patients--contra]. PMID- 20358500 TI - [Infectious endocarditis]. PMID- 20358501 TI - [Endocrine regulation in critically ill patients]. AB - Disturbances of the hormonal regulation of critically ill patients are known since many years. In the last years, two topics received a lot of attention since a single intervention led to a mortality benefit: the intensive blood glucose control in surgical intensive care patients and the low dose hydrocortisone therapy in sepsis. These results were quickly incorporated in guidelines. However, large multi-center studies failed to support the initial results in several points. This review discusses these and other disturbances of endocrine regulation of critically ill patients. PMID- 20358503 TI - [Metabolic disturbances in liver cirrhosis: hepatogenous diabetes]. PMID- 20358504 TI - Energy expenditure, lipid profile, oxidative stress, and cardiac energy metabolism after growth hormone treatment in obese young rats. AB - Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n=16): control (C) was fed standard-chow and water and hypercaloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n=8): C+PL was fed standard-chow, water and received saline subcutaneously; C+GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H+PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H+GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H+PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C+PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO (2))/body weight. H+GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H+PL. Comparing C+GH with C+PL, despite no effects on morphometric parameters, lipid profile, myocardial LH, and LDH activity, GH enhanced fed RMR and myocardial pyruvate dehydrogenase. In conclusion, the present study brought new insights into the GH effects on obesity related cardiovascular damage demonstrating, for the first time, that GH regulated cardiac metabolic pathways, enhanced energy expenditure and improved the lipid profile in obesity condition. Growth hormone in standard fed condition also offered promising therapeutic value enhancing pyruvate-dehydrogenase activity and glucose oxidation in cardiac tissue, thus optimizing myocardial energy metabolism. PMID- 20358505 TI - Varicosis of the venous epidural plexus caused by portocaval hypertension mimicking symptomatic lumbar disc herniation: case report and review of the literature. PMID- 20358506 TI - Rosette-forming glioneuronal tumor of the fourth ventricle. PMID- 20358507 TI - Intramuscular infiltrating lipoma of the longus colli muscle. a very rare cause of neck structures compression. PMID- 20358508 TI - [Violent patients: what to do? How to react?]. PMID- 20358509 TI - Radiofrequency neurotomy for headache stemming from the zygapophysial joints C2/3 and C3/4. AB - BACKGROUND: Headaches are a major socio-economic problem, and reliable and effective treatments may have an important economic impact. While many studies have investigated neck pain stemming from the zygapophysial joint, there is little data on the specific problem of headache from the zygapophysial joint C3/4. METHODS: In this investigation we included only patients who suffered from chronic headaches which had lasted for at least 12 months and were due to irritation of the zygapophysial joints (facets) of the upper cervical spine. As we aimed to prove the effectiveness of radiofrequency neurotomy in these patients, we had no randomized control group. Patients with the following underlying diseases were included in the study group: cervical fusions (followed by pseudoarthrosis); traumatic cervical fractures (not fused); arthritis. RESULTS: We examined the extent of pain relief on the first day after radiofrequency treatment and the duration of pain relief until recurrence of 50% of pre-coagulation pain in the whole collective and the three subgroups. CONCLUSIONS: Our results indicate that this therapy is effective in patients with underlying diseases of primarily degenerative origin. A significant finding was that in the group of patients with arthritis, the duration and extent of pain relief were extremely short compared to the other two groups (p<0.005, U-test). PMID- 20358510 TI - Isolated lympho-histiocytic inflammation of the Gasserian ganglion mimicking trigeminal schwannoma. AB - We present an unusual case of a patient with trigeminal pain and hypesthesia suggesting trigeminal schwannoma, where histology demonstrated an inflammatory lesion of the Gasserian ganglion. CLINICAL PRESENTATION: Patient history and imaging were typical for a trigeminal schwannoma with a dumbbell growth in the middle and posterior fossa. Surgery was performed and resection of a firm mass intermingled with fascicles originating from the ganglion and the mandibular branch was carried out via a subtemporal approach. Histological diagnosis revealed a non-caseating, vaguely granulomatous lymphocyte- and histiocyte-rich inflammation. CONCLUSION: Inflammatory lesions of the Gasserian ganglion are rare but may mimic tumors. Intraoperative biopsies should be taken prior to complete resection to limit neurological deterioration. PMID- 20358511 TI - Fusiform aneurysm of the proximal anterior cerebral artery (A1). AB - OBJECTIVE: Fusiform aneurysms of the A1 segment of the anterior cerebral artery (ACA) are exceptional, with only 15 reported cases. This article presents an additional case treated by microsurgical trapping. The aim is to discuss the treatment of these aneurysms based on the aneurysm morphology and the anatomy of the ACA complex. CASE REPORT: A 52-year-old woman with subarachnoid hemorrhage (Hunt-Hess grade II) showed an aneurysm of the proximal part of the A1 segment of the left ACA involving the whole circumference of the arterial wall on computerized tomography angiography and digital angiography. There was good collateral blood flow from the right ACA to the distal left ACA. A left pterional craniotomy allowed us to expose a large aneurysm of the proximal part of the A1 segment; the artery entered into the aneurysm sac and could not be identified at the level of the aneurysm. Trapping of the aneurysm was performed with a distal clip placed just before the origin of the artery of Heubner. No neurological deficits were observed postoperatively. CONCLUSION: Clipping of fusiform aneurysms of the A1 segment using an encircling clip is the treatment of choice but, more often, this is impossible. Trapping of the aneurysm with preservation of the perforating branches (mainly the Heubner artery) may be easily performed when collateral blood flow from the contralateral ACA is sufficient. PMID- 20358512 TI - Just say 'No' to soylent green medicine-you'll be glad you did. PMID- 20358513 TI - [Assessment of chronic abdominal pain]. PMID- 20358515 TI - [ A. Burkhart, P.A. Krayenbuhl, P.M. Suter. Vitamin-B12 deficiency. Continuing medical education. Praxis 2010; 99: 5-12]. PMID- 20358516 TI - [Breast cancer: screening, treatment and follow-up]. AB - Treatment of breast cancer is complex and needs multidisciplinarity. Preferably it should be performed in breast cancer units. Chemo-/endocrine treatment modalities are chosen by the targets (eg hormone receptors, Her2 receptor) and not by the risk any more (bi-annual St. Galler Konsensus meeting). The choice of local and systemic treatment should be adapted to the patient's conditions (age, co-morbidities, sometimes preferences) and must strongly consider the risk of relapse. Treatment of breast cancer patients is demanding and requires knowledge and skills, both of which is best available in breast cancer units. PMID- 20358517 TI - [Pathogenesis of functional gastrointestinal disorders - an interdisciplinary perspective]. AB - Functional gastrointestinal disorders (FGD) are highly prevalent worldwide. Recent research demonstrates that complex and interacting biological and behavioral mechanisms contribute particularly to the pathogenesis of irritable bowel syndrome and functional dyspepsia. Dysregulation of the enteral, neuroenteric, visceral-autonomic, and central nervous systems are important biological contributors, whereas the psychological state of a patient may evidently modulate aspects related to biological stress reactivity and somatic perception both playing a role in the clinical manifestation of FGD. Our overview clearly shows that an interdisciplinary perspective of the pathogenesis of FGD may best serve clinicians and patients. PMID- 20358518 TI - [Oral anticoagulation in the elderly - practical aspects and risk-benefit trade off in atrial fibrillation]. AB - Use of oral anticoagulants is common in elderly persons. Oral anticoagulation can be used safely in the elderly if careful titration of the loading dose, careful changes in maintenance doses as well as consideration of drug interactions are taken into account. Frequent monitoring of the INR is essential, especially with changes in medical status and in co-medication. Correction of elevated INRs can be done following the recommendations. If vitamin K is used in stable patients, only small doses are required. In patients with atrial fibrillation, ischemic stroke risk and bleeding risk are predicted by overlapping factors. So patients who profit most from stroke risk reduction also show high bleeding risk. Risk stratification for ischemic stroke can be done easily with CHADS2-Score. Fall risk tends to be overestimated as a contraindication, whereas cognitive decline in combination with an unstable social network argues against anticoagulation. In the end, the decision to start or withhold anticoagulation has to be taken individually. PMID- 20358519 TI - [Treatment of the injured patient with ankylosing spondylitis]. PMID- 20358520 TI - [A diagnosis of coeliac disease can hide an alternative diagnosis]. AB - The Common variable Immunodeficiency (CVID) is next to the selective IgA deficiency the most frequent primary immunodeficiency syndrome. Because of its variable clinical manifestations and age of declaration, CVID can mimic different other pathologies and is therefore frequently diagnosed in a later stage of the disease. However, as a consequence of late diagnosis, irreversible organ damage can have occurred which could have been prevented by early treatment. Therefore, early diagnosis of CVID by the general practitioner in patients with recurrent infections or other typical clinical manifestations is of great importance. PMID- 20358521 TI - [Age itself is not a contraindication to anticoagulation in patients with atrial fibrillation]. PMID- 20358522 TI - [Risk and duration of high risk period for postoperative thromboembolism in middle-aged women is substantial]. PMID- 20358524 TI - [The physician's literature puzzle]. PMID- 20358525 TI - [The physician's art column]. PMID- 20358528 TI - One-step fabrication of triple-layered polymeric microparticles with layer localization of drugs as a novel drug-delivery system. AB - Particulate systems have tremendous potential to achieve controlled release and targeted delivery of drugs. However, conventional single-layered particles have several inherent limitations, including initial burst release, the inability to provide zero-order release, and a lack of time-delayed or pulsatile release of therapeutic agents. Multilayered particles have the potential to overcome these disadvantages. Herein, it is shown how triple-layered polymeric microparticles can be fabricated through a simple, economical, reliable, and versatile one-step solvent evaporation technique. Particle morphologies and layer configurations are determined by scanning electron microscopy, polymer dissolution tests, and Raman mapping. Key fabrication parameters that affect the formation of triple-layered polymeric microparticles comprising poly(DL-lactide-co-glycolide) (50:50), poly(L lactide), and poly(ethylene-co-vinyl acetate) (40 wt% vinyl acetate) are discussed, along with their formation mechanisms. Layer thickness and the configurations of these microparticles are altered by changing the polymer mass ratios. Finally, it is shown that drugs can be localized in specific layers of the microparticles. This fabrication process can therefore be used to tailor microparticle designs, thus allowing such "designer" particulate drug-delivery systems to function across a wide range of applications. PMID- 20358529 TI - Aligned, ultralong single-walled carbon nanotubes: from synthesis, sorting, to electronic devices. AB - Aligned, ultralong single-walled carbon nanotubes (SWNTs) represent attractive building blocks for nanoelectronics. The structural uniformity along their tube axis and well-ordered two-dimensional architectures on wafer surfaces may provide a straightforward platform for fabricating high-performance SWNT-based integrated circuits. On the way towards future nanoelectronic devices, many challenges for such a specific system also exist. This Review summarizes the recent advances in the synthesis, identification and sorting, transfer printing and manipulation, device fabrication and integration of aligned, ultralong SWNTs in detail together with discussion on their major challenges and opportunities for their practical application. PMID- 20358530 TI - Bulk electron transport and charge injection in a high mobility n-type semiconducting polymer. PMID- 20358531 TI - Interface-directed self-assembly of cell-laden microgels. AB - Cell-laden hydrogels show great promise for creating engineered tissues. However, a major shortcoming with these systems has been the inability to fabricate structures with controlled micrometer-scale features on a biologically relevant length scale. In this Full Paper, a rapid method is demonstrated for creating centimeter-scale, cell-laden hydrogels through the assembly of shape-controlled microgels or a liquid-air interface. Cell-laden microgels of specific shapes are randomly placed on the surface of a high-density, hydrophobic solution, induced to aggregate and then crosslinked into macroscale tissue-like structures. The resulting assemblies are cell-laden hydrogel sheets consisting of tightly packed, ordered microgel units. In addition, a hierarchical approach creates complex multigel building blocks, which are then assembled into tissues with precise spatial control over the cell distribution. The results demonstrate that forces at an air-liquid interface can be used to self-assemble spatially controllable, cocultured tissue-like structures. PMID- 20358533 TI - Technetium-99m-sestamibi redistribution after exercise stress test identified by a novel cardiac gamma camera: two case reports. AB - Single photon emission computer tomography (SPECT) myocardial perfusion imaging (MPI) employing technetium-99m (Tc-99m)-based imaging tracers is the mainstay of nuclear cardiology for the detection of myocardial ischemia. Current guidelines for same day rest/stress Tc-99m-sestamibi SPECT MPI recommend image acquisition 15-60 minutes after the stress testing. A novel sensitive SPECT imaging technique, D-SPECT, allows fast acquisition of images and captures rapid changes in radiotracer distribution. Here we report 2 cases of SPECT MPI in patients with angiographically confirmed coronary artery disease (CAD) where Tc-99m-sestamibi exhibited marked redistribution between early (6-8 min) and late (60-70 min) post stress imaging leading to an underestimation of the extent and severity of ischemia on late images. These observations suggest that early imaging maybe more sensitive for CAD detection. Fast SPECT imaging techniques, such as D-SPECT, will facilitate similar studies in the future as they will allow fast image acquisition at several time points after the stress test. PMID- 20358534 TI - Increased restenosis rates 12 months after coronary implantation of the sirolimus eluting YUKON-choice stent compared to the paclitaxel-eluting TAXUS Stent. AB - BACKGROUND: Previously the polymer-free sirolimus-eluting YUKON-Choice stent (A) has demonstrated noninferiority compared to the polymer-based paclitaxel-eluting TAXUS stent (B). To test for long-term equivalency in unselected real-world coronary lesions of various complexities, we retrospectively compared both stents. METHODS: A total of 410 patients with symptomatic coronary artery disease (CAD) were treated with stent A (n = 205) or stent B (n = 205). Baseline clinical characteristics, lesion location, and length and the number of stents implanted per lesion were equally distributed. Clinical follow-up with assessment of major adverse cardiac events (MACE) and noncardiac deaths was obtained at 9 and 12 months. RESULTS: Nominal stent diameter and nominal length of the stented segment were without differences between the groups. The incidence of MACE after 12 months was significantly higher in group A (35.1%) compared to group B (16.6%, P = .001). This was mainly due to increased rates of target-lesion revascularizations in group A (13.7%) vs group B (4.4%, P = .005). No significant differences in target-vessel revascularizations and non-target-vessel revascularizations were observed. In group B, 1 stent thrombosis was documented (0.5%) vs none in group A (P > .05); in each group 1 myocardial infarction (MI), but no cardiac deaths occurred; 3 noncardiac deaths in group A (1.5%) vs 7 in group B (3.4%) were observed (P = .3). CONCLUSIONS: In contrast to our previous findings indicating no differences in MACE between patients treated with the polymer-free sirolimus-eluting YUKON-Choice stent and the polymer-based paclitaxel-eluting TAXUS stent at 6 months, we herewith show that 12 months after percutaneous coronary intervention (PCI) of real-world coronary lesions the YUKON stent appears to be inferior due to increased target-lesion revascularization (TLR) rates as a consequence of delayed restenosis. PMID- 20358535 TI - Evaluation of the surface ECG in detecting isthmus conduction block after ablation of typical atrial flutter. AB - OBJECTIVES: To investigate the value of changes in P wave morphology and duration detected by surface electrocardiogram (ECG) during proximal coronary sinus (PCS) and low lateral right atrial (LLRA) stimulation as a marker for complete bidirectional isthmus conduction block in the procedure of typical atrial flutter ablation. METHODS: Morphology, duration, and ratio of a positive terminal P wave were estimated in 52 typical atrial flutter patients before and after radiofrequency catheter ablation (RFCA). RESULTS: Atrial flutter ablation resulted in a complete bidirectional isthmus block in all 52 patients. The terminal portion of the P wave towards a positive morphology was detected in 90.7% (47/52) patients both during PCS and LLRA stimulation. These changes were predominantly observed in the inferior leads. Positive morphological changes of the terminal P wave portion and the measured P wave ratio (40% +/- 12%) in the inferior leads indicating bidirectional isthmus conduction block with a sensitivity of 87.5% and a specificity of 91.7% were observed. An increment of 20 ms or more in P wave duration during the PCS stimulation and 10 ms or more during the LLRA stimulation indicating the conduction block with a sensitivity of 90% and a specificity of 100%. CONCLUSIONS: The variation of P wave morphology and duration in inferior leads of the surface ECG is a helpful technique to assess the complete bidirectional isthmus conduction block in the procedure of typical atrial flutter ablation. PMID- 20358536 TI - Thrombus in sirolimus-eluting stent identified by optical coherence tomography. PMID- 20358537 TI - Study on amino amides and enzyme kinetics of L-asparaginase by MCE. AB - Seven kinds of amino amides including three synthetic arylglycine amides and four normal amino amides were successfully separated by MCE with LIF detector. Using micellar electrokinetic electrophoresis, the optimized separation of the seven kinds of amino amides was achieved with FITC as the labeling reagent and polyoxyethylene lauryl ether as the surfactant in 20.0 mM borate at pH 9.2. Under the optimized conditions, linearity of L-asparagine was obtained in the range of 6.6x10(-6)-2.6x10(-4) M; the detection limit (S/N=3) was 0.7 muM. The enzyme kinetic constants of L-asparaginase using L-asparagine as substrate were also determined by this method and the kinetic parameter K(m) and V(max) for the enzymatic hydrolysis of L-asparagine were 442.0 microM and 69.9 microM/min, respectively. PMID- 20358538 TI - Investigations on the migration behavior of insulin and related synthetic analogues in CZE, MEKC and MEEKC employing different surfactants. AB - The retention/migration behavior of insulin and five synthetic insulin analogues in CZE, MEKC and MEEKC employing seven different detergents within the latter two techniques has been investigated. Substantial changes in separation selectivity in MEKC could be observed for several insulins when moving from SDS to cholate based micellar systems. Customized separations could be achieved by using mixtures of SDS and deoxycholate. A similar effect could be observed in MEEKC although the overall quality of MEEKC separations was inferior to those obtained with MEKC. PMID- 20358539 TI - Peak parking determination of the obstruction factor in lauryl acrylate monolithic CEC columns. AB - The peak parking method was used to determine the obstruction factor of lauryl acrylate porous polymer monoliths. Polymers were prepared in situ in fused-silica capillaries using thermally initiated polymerization. These columns have been used for CEC of neutral analytes. Thiourea, which is unretained, was used as the test analyte for the obstruction factor measurement. The obstruction factor was determined to be 0.72 with a SD of (+/-0.01), which is consistent with the concept that organic porous polymer monoliths are more permeable than traditional LC stationary phases. PMID- 20358540 TI - Liposomes for entrapping local anesthetics: a liposome electrokinetic chromatographic study. AB - Bupivacaine is a lipophilic, long-acting, amide class local anesthetic commonly used in clinical practice to provide local anesthesia during surgical procedures. Several cases of accidental overdose with cardiac arrest and death have been reported since bupivacaine was introduced to human use. Recent case reports have suggested that Intralipid (Fresenius Kabi) is an effective therapy for cardiac toxicity from high systemic concentrations of, e.g. bupivacaine, even though the mechanism behind the interaction is not fully clear yet. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances in vivo. In this study, the in vitro interaction of local anesthetics (bupivacaine, prilocaine, and lidocaine) with Intralipid or lipid vesicles containing phosphatidylglycerol, phosphatidylcholine, cardiolipin, cholesterol, and N-palmitoyl-D-erythro sphingosine (ceramide) was determined by liposome electrokinetic chromatography. The interactions were evaluated by calculating the retention factors and distribution constants. Atomic force microscopy measurements were carried out to confirm that the interaction mechanism was solely due to interactions between the analytes and the moving pseudostationary phase and not by interactions with a stationary lipid phase adsorbed to the fused-silica wall. The heterogeneity of the liposomes was also studied by atomic force microscopy. The liposome electrokinetic chromatography results demonstrate that there is higher interaction between the drugs and negatively charged liposome dispersion than with the commercial Intralipid dispersion. PMID- 20358541 TI - New capillary coatings in open tubular CEC as models for biological membranes. AB - Novel stationary phases in open tubular CEC were investigated. The coating procedure was fast and simple. The coating material contained membrane suspension of different neuronal cell lines. The performance and stability of three cell lines: human neuroblastoma SH-SY5Y, murine microglia Bv-2 and human glioma U87-MG cells were studied. The coating solution was expected to contain both membrane proteins and membrane lipids. The presence of membrane proteins was tested by Western blotting and the presence of phospholipids by the analysis of phosphorus content. The stability of the coating was estimated by monitoring the mobility of EOF over successive runs. The effects of pH, storage time and temperature on the coating stability were also studied. The results showed that the cell membrane based coating was stable over pH range of 6.5-8.5. Coatings derived from different cells yielded similar stability and EOF mobility. Capillary coated with a membrane solution was stable over 3-day period. The same coating solution could be used for 3 weeks. PMID- 20358542 TI - Development of a PDMS-based microchip electrophoresis device for continuous online in vivo monitoring of microdialysis samples. AB - A PDMS-based microfluidic system for online coupling of microdialysis sampling to microchip electrophoresis with fluorescence detection for in vivo analysis of amino acid neurotransmitters using naphthalene-2,3-dicarboxaldehyde and sodium cyanide as the derivatization reagents is described. Fabricating chips from PDMS rather than glass was found to be simpler and more reproducible, especially for chips with complex designs. The microchip incorporated a 20-cm serpentine channel in which sample plugs were introduced using a "simple" injection scheme; this made fluid handling and injection on-chip easier for the online system compared with gated or valve-based injection. The microchip was evaluated offline for the analysis of amino acid standards and rat brain microdialysis samples. Next, precolumn derivatization was incorporated into the chip and in vivo online microdialysis-microchip electrophoresis studies were performed. The system was employed for the continuous monitoring of amino acid neurotransmitters in the extracellular fluid of the brain of an anesthetized rat. Fluorescein was dosed intravenously and monitored simultaneously online as a marker of in vivo blood brain barrier permeability. The microdialysis-microchip electrophoresis system described here will be employed in the future for simultaneous monitoring of changes in blood-brain barrier permeability and levels of amino acid neurotransmitters in the rat stroke model. PMID- 20358543 TI - Enantioselective CE analysis of hepatic ketamine metabolism in different species in vitro. AB - Ketamine, an injectable anesthetic and analgesic consisting of a racemic mixture of S-and R-ketamine, is routinely used in veterinary and human medicine. Nevertheless, metabolism and pharmacokinetics of ketamine have not been characterized sufficiently in most animal species. An enantioselective CE assay for ketamine and its metabolites in microsomal preparations is described. Racemic ketamine was incubated with pooled microsomes from humans, horses and dogs over a 3 h time interval with frequent sample collection. CE data revealed that ketamine is metabolized enantioselectively to norketamine (NK), dehydronorketamine and three hydroxylated NK metabolites in all three species. The metabolic patterns formed differ in production rates of the metabolites and in stereoselectivity of the hydroxylated NK metabolites. In vitro pharmacokinetics of ketamine N demethylation were established by incubating ten different concentrations of racemic ketamine and the single enantiomers of ketamine for 8 min and data modeling was based on Michaelis-Menten kinetics. These data revealed a reduced intrinsic clearance of the S-enantiomer in the racemic mixture compared with the single S-enantiomer in human microsomes, no difference in equine microsomes and the opposite effect in canine microsomes. The findings indicate species differences with possible relevance for the use of single S-ketamine versus racemic ketamine in the clinic. PMID- 20358544 TI - Determination of glyphosate and its metabolites in plant material by reversed polarity CE with indirect absorptiometric detection. AB - A simple CE method for simultaneous determination of glyphosate and its metabolites (i.e. aminomethylphosphonic acid, glyoxylate, sarcosine and formaldehyde) in plants is reported here. A BGE of pH 7.5, 10% ACN, 7.5 mM phthalate, containing 0.75 mM hexadecyltrimethylammonium bromide as an electro osmotic flow modifier, an applied voltage of -20 kV and absorptiometric monitoring at 220 nm were the optimal chemical and instrumental parameters. The method, with development time 20 min, shows linear calibrations within the range 5-500 microg/mL (for all target analytes) with correlation coefficients between 0.999 and 0.998. It has been validated by application to samples of Lolium spp. The electroinjection mode hinders most interferents to enter the capillary, thus providing a clean electropherogram and making unnecessary long sample-preparation steps. PMID- 20358545 TI - Simultaneous analysis of multiple PCR amplicons enhances capillary SSCP discrimination of MHC alleles. AB - Major histocompatibility complex (MHC) genotyping still remains one of the most challenging issues for evolutionary ecologists. To date, none of the proposed methods have proven to be perfect, and all provide both important pros and cons. Although denaturing capillary electrophoresis has become a popular alternative, allele identification commonly relies upon conformational polymorphisms of two single-stranded DNA molecules at the most. Using the MHC class II (beta chain, exon 2) of the black kite (Aves: Accipitridae) as our model system, we show that the simultaneous analysis of overlapping PCR amplicons from the same target region substantially enhances allele discrimination. To cover this aim, we designed a multiplex PCR capable to generate four differentially sized and labeled amplicons from the same allele. Informative peaks to assist allele calling then fourfold those generated by the analysis of single PCR amplicons. Our approach proved successful to differentiate all the alleles (N=13) isolated from eight unrelated birds at a single optimal run temperature and electrophoretic conditions. In particular, we emphasize that this approach may constitute a straightforward and cost-effective alternative for the genotyping of single or duplicated MHC genes displaying low to moderate sets of divergent alleles. PMID- 20358546 TI - Maleopimaric acid anhydride-bonded silica monolith as chiral stationary phase for separations of phenylthiocarbamyl amino acids by CEC. AB - A new type of chiral silica monolith was successfully developed for the enantioseparation of phenylthiocarbamyl amino acids (PTC-(D/L)-AAs) by CEC. The bare monolithic silica column was prepared by a sol-gel process and has been modified chemically with aminopropyltrimethoxysilane, followed by immobilization of a chiral selector maleopimaric acid anhydride. Eight pairs of tested amino acids enantiomers including PTC-(D/L)-arginine, PTC-(D/L)-valine, PTC-(D/L) leucine, PTC-(D/L)-4-methylphenylalanine, PTC-(D/L)-phenylalanine, PTC-(D/L)-beta phenylalanine, PTC-(D/L)-tryptophan and PTC-(D/L)-kynurenine were well resolved with high column efficiencies. The influences of organic modifier in mobile phase on apparent retention factor, enantioselectivity factor and resolution were also investigated. PMID- 20358547 TI - CE assay for simultaneous determination of charged and neutral impurities in dexamphetamine sulfate using a dual CD system. AB - A CE assay for the simultaneous determination of charged and uncharged potential impurities (1S,2S-(+)-norpseudoephedrine, 1R,2S-(-)-norephedrine, phenylacetone and phenylacetone oxime) of dexamphetamine sulfate including the stereoisomer levoamphetamine was developed and validated. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 3.0, containing 80 mg/mL sulfobutylether-beta-CD and 25 mg/mL sulfated beta-CD. Separations were performed in 40.2/35 cm, 50 mum id fused-silica capillaries at a temperature of 20 degrees C and an applied voltage of -10 kV. 1R,2S-(-)-ephedrine was used as internal standard. The assay was validated in the range of 0.05-1.0% for the related substances and in the range of 0.05-5.0% for levoamphetamine. The LOD was 0.01 0.02% depending on the analyte. The assay also allowed the separation of the E,Z stereoisomers of phenylacetone oxime. The effect of the degree of substitution of sulfobutylether-beta-CD was investigated. In commercial samples of dexamphetamine sulfate between 3.2 and 3.7% of levoamphetamine were found. Furthermore, phenylacetone and phenylacetone oxime could be observed at the LOD, indicating the synthetic origin of the investigated samples. PMID- 20358548 TI - Separation of propranolol enantiomers by CE using sulfated beta-CD derivatives in aqueous and non-aqueous electrolytes: comparative CE and NMR study. AB - Separations using CE employing non-aqueous BGE are already as well established as separations in aqueous buffers. The separation mechanisms in achiral CE with non aqueous BGEs are most likely similar to those in aqueous buffers. However, for the separation of enantiomers involving their interaction with chiral buffer additives, the interaction mechanisms might be very different in aqueous and non aqueous BGEs. While the hypothesis regarding distinct mechanisms of enantiomer separations in aqueous and non-aqueous BGEs has been mentioned in several papers, no direct proof of this hypothesis has been reported to date. In the present study, the enantiomers of propranolol were resolved using CE in aqueous and non aqueous methanolic BGEs with two single isomer sulfated derivatives of beta-CD, namely heptakis (2,3-diacetyl-6-sulfo)-beta-CD and heptakis (2,3-dimethyl-6 sulfo)-beta-CD. The enantiomer migration order of propranolol was inverted when an aqueous BGE was replaced with non-aqueous BGE in the case of heptakis (2,3 dimethyl-6-sulfo)-beta-CD but remained the same in the case of heptakis (2,3 diacetyl-6-sulfo)-beta-CD. The possible molecular mechanisms leading to this reversal of enantiomer migration order were studied by using nuclear overhauser effect spectroscopy in both aqueous and non-aqueous BGEs. PMID- 20358549 TI - Enhanced selectivity in CZE multi-chiral selector enantioseparation systems: proposed separation mechanism. AB - It has been reported many times that the commercial mixtures of chiral selectors (CS), namely highly sulfated beta-CDs (HS-beta-CDs), provide remarkable enantioselectivity in CZE when compared with single-isomer CDs, even single isomer HS-beta-CDs. This enhanced enantioselectivity of multi-CS enantioseparative CZE is discussed in the light of multi-CS model that we have introduced earlier. It is proposed on a theoretical basis and verified experimentally that the two enantiomers of a chiral analyte under interaction with a mixture of CSs are very likely to differ in their limit mobilities, which is opposite to single-CS systems where the two limit mobilities are likely to be the same. Thus while the enantioseparation is usually controlled by different distribution constants between the two enantiomers and CS used in single-CS systems, an additional, electrophoretic, enantioselective mechanism resulting from different limit mobilities may play a significant role in multi-CS systems. This additional mechanism generally makes the multi-CS systems more selective than the single-CS systems. The possible inequality of limit mobilities is also significant for optimization of separation conditions using mixtures of CSs. A practical example supporting our considerations is shown on enantioseparation of lorazepam in the presence of a commercial mixture of HS-beta-CDs and a single isomer HS-beta-CD, heptakis(6-O-sulfo)-beta-CD. PMID- 20358550 TI - Determination of free and total levels of phenytoin in human plasma from patients with epilepsy by MEKC: an adequate alternative to HPLC. AB - Phenytoin is a widely used anti-seizure agent, and a good correlation is observed between its concentration in plasma and the clinical effect. We developed a selective CE with UV detection at 200 nm for analysis of free and total levels of phenytoin in human plasma based on MEKC. A sample pretreatment by liquid-liquid extraction with ethyl acetate for determination of total level of phenytoin and serum ultrafiltrate was prepared by ultrafiltration technique (ultrafiltration membrane 30 kDa; 2000 g, 10 min) for determination of free level of phenytoin and subsequent quantification by MEKC was used. MEKC was performed in Tris buffer (25 mM; pH 10.5) containing SDS (180 mM) and EG (13%) as BGE. Hydrodynamic injection for phenytoin determination (0.5 psi 5 s for total level, 2 psi 5 s for free level) was used to introduce samples. The separation voltage was set at 20 kV. Data obtained by MEKC were compared with the results by a validated HPLC method. The MEKC assay of phenytoin exhibited a very good correlation with respect to HPLC by Bland-Altman method. The equations for the Passing-Bablok regression line were as follows: for total level: MEKC=1.0143 x HPLC+0.0976, r(2)=1; for free level: MEKC=1.0013 x HPLC-0.0016, r(2)=1. The proposed method was applied successfully to monitor free and total levels of phentoin in 20 patients with seizures. PMID- 20358551 TI - Bayesian semiparametric frailty selection in multivariate event time data. AB - Biomedical studies often collect multivariate event time data from multiple clusters (either subjects or groups) within each of which event times for individuals are correlated and the correlation may vary in different classes. In such survival analyses, heterogeneity among clusters for shared and specific classes can be accommodated by incorporating parametric frailty terms into the model. In this article, we propose a Bayesian approach to relax the parametric distribution assumption for shared and specific-class frailties by using a Dirichlet process prior while also allowing for the uncertainty of heterogeneity for different classes. Multiple cluster-specific frailty selections rely on variable selection-type mixture priors by applying mixtures of point masses at zero and inverse gamma distributions to the variance of log frailties. This selection allows frailties with zero variance to effectively drop out of the model. A reparameterization of log-frailty terms is performed to reduce the potential bias of fixed effects due to variation of the random distribution and dependence among the parameters resulting in easy interpretation and faster Markov chain Monte Carlo convergence. Simulated data examples and an application to a lung cancer clinical trial are used for illustration. PMID- 20358553 TI - Metal-organic frameworks with exceptionally high methane uptake: where and how is methane stored? AB - Metal-organic frameworks (MOFs) are a novel family of physisorptive materials that have exhibited great promise for methane storage. So far, a detailed understanding of their methane adsorption mechanism is still scarce. Herein, we report a comprehensive mechanistic study of methane storage in three milestone MOF compounds (HKUST-1, PCN-11, and PCN-14) the CH(4) storage capacities of which are among the highest reported so far among all porous materials. The three MOFs consist of the same dicopper paddlewheel secondary building units, but contain different organic linkers, leading to cagelike pores with various sizes and geometries. From neutron powder diffraction experiments and accurate data analysis, assisted by grand canonical Monte Carlo (GCMC) simulations and DFT calculations, we unambiguously revealed the exact locations of the stored methane molecules in these MOF materials. We found that methane uptake takes place primarily at two types of strong adsorption site: 1) the open Cu coordination sites, which exhibit enhanced Coulomb attraction toward methane, and 2) the van der Waals potential pocket sites, in which the total dispersive interactions are enhanced due to the molecule being in contact with multiple "surfaces". Interestingly, the enhanced van der Waals sites are present exclusively in small cages and at the windows to these cages, whereas large cages with relatively flat pore surfaces bind very little methane. Our results suggest that further, rational development of new MOF compounds for methane storage applications should focus on enriching open metal sites, increasing the volume percentage of accessible small cages and channels, and minimizing the fraction of large pores. PMID- 20358554 TI - Solution-phase racemization in the presence of an enantiopure solid phase. AB - Solution-phase racemization drives the evolution of single chirality in the solid phase by the "chiral amnesia" process first described by Viedma. The current investigations lay the basis for a better understanding of the mechanism of the solid-phase deracemization by uncoupling the chemical rate processes associated with the interconversion of enantiomers in the solution phase from the physical processes associated with solution-solid phase transfer via dissolution and reaccretion of molecules onto crystals. In addition, the enantiomer concentration profiles presented in this work, together with an analytical treatment of the racemization process in the presence of excess enantiopure solid, unequivocally reconfirm the validity of the Meyerhoffer double solubility rule for systems under solution racemization conditions. PMID- 20358555 TI - Molecular structure of amyloid fibrils formed by residues 127 to 147 of the human prion protein. AB - Amyloid fibrils are filamentous and insoluble forms of peptides or proteins. Proline has long been considered to be incompatible with the cross-beta structural motif of amyloid fibrils. On the basis of solid-state NMR spectroscopy data, we present a structural model of an in-register parallel beta sheet for the amyloid fibrils formed from a human prion protein fragment, huPrP(127-47). We have developed a simple solid-state NMR spectroscopy technique to identify solvent-protected backbone amide protons in a H/D exchange experiment without disaggregating the amyloid fibrils, from which we find that proline residue P(137) does not disrupt the beta-sheet structure from G(127) to G(142). We suggest that the resultant kink at P(137) generates a twist between adjacent peptide strands to maintain hydrogen bonding in the beta-sheet regions flanking the P(137) residue. Although proline can be well integrated into the cross-beta structure of amyloid fibrils, the kink formed at the position of the proline residue will considerably weaken the hydrogen bonding between the neighboring strands, especially when the mutation site is near the central region of a beta sheet. PMID- 20358556 TI - Neutral and oxidized triisopropylsilyl end-capped oligothienoacenes: a combined electrochemical, spectroscopic, and theoretical study. AB - This work presents an analysis of the structural, electrochemical, and optical properties of a family of triisopropylsilyl end-capped oligothienoacenes (TIPS-Tn TIPS, n=4-8) by combining cyclic voltammetry, spectroscopic techniques, and quantum-chemical calculations. TIPS-Tn-TIPS compounds form stable radical cations, and dications are only obtained for the longest oligomers (n=7 and 8). Oxidation leads to the quinoidization of the conjugated backbone, from which electrons are mainly extracted. The absorption and fluorescence spectra show partially resolved vibronic structures even at room temperature, due to the rigid molecular geometry. Two well-resolved vibronic progressions are observed at low temperatures due to the vibronic coupling, with normal modes showing wavenumbers of approximately 1525 and approximately 480 cm(-1). Optical absorption bands display remarkable bathochromic dispersion with the oligomer length, indicative of the extent of pi conjugation. The optical properties of the oxidized compounds are characterized by in situ UV/Vis/NIR spectroelectrochemistry. The radical cation species show two intense absorption bands emerging at energies lower than in the neutral compounds. The formation of the dication is only detected for the heptamer and the octamer, and shows a new band at intermediate energies. Optical data are interpreted with the help of density functional theory calculations performed at the B3LYP/6-31G** level, both for the neutral and the oxidized compounds. PMID- 20358557 TI - Highly efficient Rh(I)-catalyzed asymmetric hydrogenation of beta-amino acrylonitriles. PMID- 20358559 TI - Catalytic asymmetric 1,3-dipolar cycloaddition of alpha-iminonitriles. PMID- 20358558 TI - Structural analysis of a helical peptide unfolding pathway. AB - The analysis of the folding mechanism in peptides adopting well-defined secondary structure is fundamental to understand protein folding. Herein, we describe the thermal unfolding of a 15-mer vascular endothelial growth factor mimicking alpha helical peptide (QK(L10A)) through the combination of spectroscopic and computational analyses. In particular, on the basis of the temperature dependencies of QK(L10A) H(alpha) chemical shifts we show that the first phase of the thermal helix unfolding, ending at around 320 K, involves mainly the terminal regions. A second phase of the transition, ending at around 333 K, comprises the central helical region of the peptide. The determination of high-resolution QK(L10A) conformational preferences in water at 313 K allowed us to identify, at atomic resolution, one intermediate of the folding-unfolding pathway. Molecular dynamics simulations corroborate experimental observations detecting a stable central helical turn, which represents the most probable site for the helix nucleation in the folding direction. The data presented herein allows us to draw a folding-unfolding picture for the small peptide QK(L10A) compatible with the nucleation-propagation model. This study, besides contributing to the basic field of peptide helix folding, is useful to gain an insight into the design of stable helical peptides, which could find applications as molecular scaffolds to target protein-protein interactions. PMID- 20358560 TI - A scanning probe microscopy study of annulated redox-active molecules at a liquid/solid interface: the overruling of the alkyl chain paradigm. PMID- 20358561 TI - Aryl phosphoramides: useful electrophiles for Suzuki-Miyaura coupling catalyzed by a NiCl2/dppp system (dppp=1,3-bis(diphenylphosphino)propane). PMID- 20358562 TI - Soluble and columnar liquid crystalline peropyrenequinones by coupling of phenalenones in caesium hydroxide. PMID- 20358563 TI - The impact of amino acid side chain mutations in conformational design of peptides and proteins. AB - Local energetic effects of amino acid replacements are often considered to have only a moderate influence on the backbone conformation of proteins or peptides. As these effects are difficult to determine experimentally, no comparison has yet been performed. However, knowledge of the influence of side chain mutations is essential in protein homology modeling and in optimizing biologically active peptide ligands in medicinal chemistry. Furthermore, the tool of N-methylation of peptides is of increasing importance for the design of peptidic drugs to gain oral availability or receptor selectivity. However, N-methylation is often accompanied by considerable population of cis-peptide bond structures, resulting in completely different conformations compared with the parent peptide. To retain a favored structure, it might be important to understand the effect of different side chains on the backbone conformation and to enable the introduction of an N methylation at the right position without disturbing a biologically active conformation. In order to detect even small energetic effects due to side chain mutations, we employed a trick to investigate the structural equilibrium of a selected cyclic pentapeptide in which two conformations are equally populated. Very small energetic differences between both conformations could easily be determined experimentally by identifying shifts in the population of both isomers. PMID- 20358564 TI - Australia's plastic banknotes: fighting counterfeit currency. PMID- 20358565 TI - Lithium-doped conjugated microporous polymers for reversible hydrogen storage. PMID- 20358567 TI - In situ stepwise synthesis of functional multijunction molecular wires on gold electrodes and gold nanoparticles. PMID- 20358566 TI - Antiplasmodial thiostrepton derivatives: proteasome inhibitors with a dual mode of action. PMID- 20358568 TI - Reductive retrofunctionalization of single-walled carbon nanotubes. PMID- 20358569 TI - The fundamental role of exchange-enhanced reactivity in C-H activation by S=2 oxo iron(IV) complexes. PMID- 20358571 TI - A simple route to univalent gallium salts of weakly coordinating anions. PMID- 20358570 TI - A highly reactive dicationic iridium(III) catalyst for the polarized Nazarov cyclization reaction. PMID- 20358572 TI - Concerted [2+2] cycloaddition of alkenes to a ruthenium-phosphorus double bond. PMID- 20358575 TI - Environmental effects in computational spectroscopy: accuracy and interpretation. AB - Spectroscopic techniques are valuable tools for understanding the structure and dynamics of complex systems, such as biomolecules or nanomaterials. Most of the current research is devoted to the development of new experimental techniques for improving the intrinsic resolution of different spectra. However, the subtle interplay of several different effects acting at different length and time scales still makes the interpretation and analysis of such spectra a very difficult task. In this respect, computational spectroscopy is becoming a needful and versatile tool for the assignment and interpretation of experimental spectra. It is in fact possible nowadays to model with relatively high accuracy the physical chemical properties of complex molecules in different environments, and to link spectroscopic evidence directly to the structural and dynamical properties of optically or magnetically active solvated probes. In this Review, significant steps toward the simulation of entire spectra in condensed phases are presented together with some basic aspects of computational spectroscopy, which highlight how intramolecular and intermolecular degrees of freedom influence several spectroscopic parameters. PMID- 20358576 TI - Synthesis and biological characterization of argyrin F. PMID- 20358577 TI - An isolated CO2 adduct of a nitrogen base: crystal and electronic structures. PMID- 20358579 TI - MicroRNAs and their role in gynecological tumors. AB - There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (~22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed. PMID- 20358578 TI - Transesterification of cyclic carbonates to dimethyl carbonate using solid oxide catalyst at ambient conditions: environmentally benign synthesis. PMID- 20358580 TI - Deeper understanding of unclassified intronic variants and ESEs. PMID- 20358584 TI - SACGHS mulls recommendations for genetics training. PMID- 20358582 TI - Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. AB - PRKAR1A encodes the regulatory subunit type 1-alpha (RIalpha) of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Inactivating PRKAR1A mutations are known to be responsible for the multiple neoplasia and lentiginosis syndrome Carney complex (CNC). To date, at least 117 pathogenic variants in PRKAR1A have been identified (online database: http://prkar1a.nichd.nih.gov). The majority are subject to nonsense mediated mRNA decay (NMD), leading to RIalpha haploinsufficiency and, as a result, activated cAMP signaling. Recently, it became apparent that CNC may be caused not only by RIalpha haploinsufficiency, but also by the expression of altered RIalpha protein, as proven by analysis of expressed mutations in the gene, consisting of amino acid substitutions and in-frame genetic alterations. In addition, a new subgroup of mutations that potentially escape NMD and result in CNC through altered (rather than missing) protein has been analyzed-these are frame-shifts in the 3' end of the coding sequence that shift the stop codon downstream of the normal one. The mutation detection rate in CNC patients is recently estimated at above 60%; PRKAR1A mutation-negative CNC patients are characterized by significant phenotypic heterogeneity. In this report, we present a comprehensive analysis of all presently known PRKAR1A sequence variations and discuss their molecular context and clinical phenotype. PMID- 20358585 TI - New test could make carrier screening more accessible. PMID- 20358586 TI - Tsukahara syndrome established as specific diagnosis. PMID- 20358587 TI - Molecular and functional analysis of a novel MEK2 mutation in cardio-facio cutaneous syndrome: transmission through four generations. AB - Cardio-facio-cutaneous (CFC) syndrome is one of the RASopathies and is caused by alteration of activity through the Ras/mitogen-activated protein kinase (MAPK) pathway due to heterozygous de novo mutations in protein kinases BRAF, MEK1, or MEK2. CFC is a rare multiple congenital anomaly disorder in which individuals have characteristic dysmorphic features, cardiac defects, ectodermal anomalies and developmental delay.We report a 7(1/2)-month-old boy with a clinical diagnosis of CFC. Bidirectional sequence analysis of MEK2 revealed a novel c.383C ->A transversion in exon 3 resulting in a nonsynonymous missense substitution, p.P128Q. Other family members, including the proband's mother and half-sibling, displayed phenotypic features of CFC and were also screened for the MEK2 mutation identified in the proband. Sorting Intolerant From Tolerant (SIFT) analysis determined the novel MEK2 p.P128Q to be deleterious. To corroborate the functional alteration of the novel mutant protein, transient transfection of HEK 293T cells with subsequent Western analysis was used to demonstrate increased kinase activity, as measured by ERK phosphorylation. This first reported case of a vertically transmitted functional CFC MEK mutation further expands our understanding of germline mutations within the Ras/MAPK pathway. PMID- 20358588 TI - Ultrasound diagnosis of severe mesomelic dysplasia in two fetuses, associated with increased neck translucency and tetralogy of Fallot in one and cystic hygroma in the other. AB - Two stillborn male sibling fetuses born to the same parents had severe mesomelic dysplasia documented at ultrasound and confirmed by radiography and autopsy. The 17-week-old fetus with increased neck translucency had additional heart and great vessel anomalies consistent with tetralogy of Fallot. The 15-week-old fetus had a nuchal cystic hygroma. We posit that these sibs have a distinct, previously unreported skeletal dysplasia. The mode of genetic transmission could be autosomal recessive or X-linked recessive. PMID- 20358589 TI - Commentary: The second step in syndrome delineation: who belongs and who does not? Thoughts generated by the paper on Floating-Harbor syndrome by White and colleagues. PMID- 20358590 TI - The phenotype of Floating-Harbor syndrome in 10 patients. AB - Floating-Harbor syndrome (FHS) is a rare condition typified by short stature, speech impairment, delayed bone age, and characteristic facies. The diagnosis can be difficult as the facial changes are subtle in infancy, and the features of short stature, delayed speech, and delayed bone age are frequently encountered in clinical practice. We refine the phenotype in FHS by reporting clinical findings in 10 typically affected individuals ranging in age from 7 to 34 years and present a mother and daughter who display some features of FHS. Bone age measurements were delayed when measured from age 6 months to 6 years but in some patients were normal between 6 and 12 years. Dysmorphic features at different ages are characterized. The lateral profile of the face and the characteristic body habitus aided diagnosis. Significant behavioral problems of hyperactivity, short attention span and aggression during childhood were reported for most individuals. The children studied had a severe and incapacitating disorder of speech and language. Intellectual functioning ranged from borderline normal to moderate intellectual disability. Early puberty was noted. Adult heights were 140 155 cm. Microarray analysis in eight of the patients provided no evidence that FHS is caused by a large-scale copy-number genomic change. PMID- 20358591 TI - PAX2 mutations in fetal renal hypodysplasia. AB - Papillorenal syndrome also known as renal-coloboma syndrome (OMIM 120330) is an autosomal dominant condition comprising optic nerve anomaly and renal oligomeganephronic hypoplasia. This reduced number of nephron generations with compensatory glomerular hypertrophy leads towards chronic insufficiency with renal failure. We report on two fetuses with PAX2 mutations presenting at 24 and 18 weeks' gestation, respectively, born into two different sibships. In our first patient, termination of pregnancy was elected for anhydramnios and suspicion of renal agenesis in the healthy couple with an unremarkable previous clinical history. This fetus had bilateral asymmetric kidney anomalies including a small multicystic left kidney, and an extremely hypoplastic right kidney. Histology showed dysplastic lesions in the left kidney, contrasting with rather normal organization in the hypoplastic right kidney. Ocular examination disclosed bilateral optic nerve coloboma. The association of these anomalies, highly suggestive of the papillorenal syndrome, led us to perform the molecular study of the PAX2 gene. Direct sequencing of the PAX2 coding sequence identified a de novo single G deletion of nucleotide 935 in exon 3 of the PAX2 resulting in a frameshift mutation (c.392delG, p.Ser131Thrfs*28). In the second family, the presence of a maternally inherited PAX2 mutation led to a decision for termination of pregnancy. The 18-week gestation fetus presented the papillorenal syndrome including hypoplastic kidneys and optic nerve coloboma. In order to address the PAX2 involvement in isolated renal "disease," 18 fetuses fulfilling criteria were screened: 10/18 had uni- or bilateral agenesis, 6/18 had bilateral multicystic dysplasia with enlarged kidneys, and 2/18 presented bilateral severe hypodysplasia confirmed on fetopathological examination. To the best of our knowledge, our first patient represents an unreported fetal diagnosis of papillorenal syndrome, and another example of the impact of oriented fetopathological examination in genetic counseling of the parents. PMID- 20358592 TI - Development of a culturally tailored genetic counseling booklet about hereditary breast and ovarian cancer for Black women. AB - Printed educational materials (PEM) can serve as important tools to enhance and reinforce information presented during genetic counseling (GC) for BRCA1/2 testing, yet few such materials have been specifically developed for the Black community. The goal of the current study was to develop a BRCA1/2 genetic education booklet for Black women at increased risk for hereditary breast and ovarian cancer (HBOC). Investigators identified available PEM about BRCA1/2 targeted toward Blacks. To obtain possible perspectives of the target population regarding modified and newly developed materials, a Community Advisory Panel (CAP) comprising breast cancer survivors, advocates, and community leaders was convened. While the CAP felt PEM were an important adjunct to GC, the panel recommended developing materials that were more personalized and relevant to Black women. A 12-page booklet that follows the flow of a standard GC session was developed; it includes a limited amount of technical information, incorporates familiar terms and images to describe key concepts, and contains vignettes and photographs of Black women. Upon review of the newly developed booklet, CAP members agreed their input had been well implemented, and only had minor suggestions. The booklet is currently being used in a population-based study of BRCA1/2 mutations among Black women diagnosed with early-onset breast cancer. Involving members of the target community is critical to the development of culturally tailored PEM. Further evaluation of the utility of our booklet in increasing awareness and understanding of HBOC and promoting informed decision making regarding genetic testing and medical management among Black women is needed. PMID- 20358593 TI - Identification of susceptibility loci for scoliosis in FIS families with triple curves. AB - The triple curve pattern (three lateral curvatures of equal severity) has been recognized as a distinct and unique clinical subtype of scoliosis. As part of a large study of familial idiopathic scoliosis (FIS), a subset of five families with a triple curve pattern (at least one member of each family having a triple curve) was evaluated to determine if this curve pattern was linked to any of the markers previously genotyped as part of the STRP-based previous linkage screen. Model independent linkage analysis (SIBPAL, v4.5) of the initial genomic screen identified candidate regions on chromosomes 6 and 10 when FIS was analyzed both as qualitative and quantitative traits in single- and multipoint linkage analyses. Additional fine mapping analyses of this subgroup with SNPs corroborated the findings in these regions (P < 0.001). These regions have been previously linked to FIS, however, this is the first time these regions have been implicated in a clinically well-defined subgroup and may suggest a unique genetic etiology for the formation of a triple curve. PMID- 20358594 TI - Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. AB - Nonsyndromic oral cleft is a common developmental malformation of humans. Embryonic development is regulated by microRNAs. MicroRNA-140-5p (miR-140-5p) was found to regulate palatal development. As sequence variants in miRNA genes are likely to affect miRNA expression and/or maturation, we investigated the miRNA 140 gene and identified a SNP (rs7205289: C>A) located in precursor miRNA-140. We carried out a case-control analysis in 557 patients with nonsyndromic oral clefts and 306 unaffected controls from west China and found that the frequency of minor allele (A allele) was significantly increased (P = 0.003 after Bonferroni correction) in nonsyndromic cleft palate (NSCP) patients in comparison with that in controls. We constructed expression vectors of primary miRNA-140 (pri-miR-140) with the major and minor alleles of rs7205289. The vectors were transfected into HEK293 cells, and the mature forms of miR-140 were detected by Northern blot. Compared to the vector with the C allele, the vector with the A allele was found to influence the miR-140 processing, resulting in a significant decrease of miR 140-5p and an increase of miR-140-3p. These results suggest that the SNP located in pre-miR-140 contributes to NSCP susceptibility by influencing the processing of miR-140. PMID- 20358595 TI - Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy. AB - Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix protein, and matrilin 3: COL9A1, COL9A2, COL9A3, COMP, and MATN3, respectively. Splicing mutations have been identified in all three genes encoding type IX collagen and are restricted to specific exons encoding an equivalent region of the COL3 domain in all three alpha(IX) chains. MED has been associated with mild myopathy in some families, in particular one family with a COL9A3 mutation and two families with C-terminal COMP mutations. In this study we have identified COL9A2 mutations in two families with MED that also have osteochondritis dissecans and mild myopathy. This study therefore extends the range of gene-mutations that can cause MED-related myopathy. (c) 2010 Wiley-Liss, Inc. PMID- 20358596 TI - Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. AB - Craniometaphyseal dysplasia (CMD) is a rare, sclerosing skeletal disorder caused by mutations in ANKH, which encodes a putative pyrophosphate transporting membrane protein. Six distinct ANKH mutations have been described to date. We report here on three novel mutations in simplex patients with CMD. The c.1015T>C (p.Cys339Arg) mutation found in Patient A was associated with congenital facial palsy, early-onset conductive hearing loss, and a generalized undermodeling of the long bones. The c.1172T>C (p.Leu391Pro) mutation in Patient B was associated with facial palsy, progressive conductive hearing loss, and generalized undermodeling of tubular bones. A milder phenotype without cranial nerve affection was observed in Patient C, associated with a c.1001T>G (p.Leu334Arg) mutation. All affected residues lie in evolutionarily conserved sequence blocks. These additional cases and the associated mutations contribute to an improved appreciation of the variability of this rare skeletal dysplasia. (c) 2010 Wiley Liss, Inc. PMID- 20358597 TI - A variant of Desbuquois dysplasia characterized by advanced carpal bone age, short metacarpals, and elongated phalanges: report of seven cases. AB - We present the clinical and radiological findings of seven patients with a seemingly new variant of Desbuquois dysplasia (DBQD) and emphasize the radiographic findings in the hand. All cases showed remarkably accelerated carpal bone ages in childhood, but none of the patients had an accessory ossification center distal to the second metacarpal, or thumb anomalies, instead, there was shortness of one or all metacarpals, with elongated appearance of phalanges, resulting in nearly equal length of the second to fifth fingers. The two sibs followed for 20 years showed narrowing and fusion of the intercarpal joints with age and ultimately, precocious degenerative arthritis. The changes in the feet were similar to those of the hands, with advanced tarsal bone ages, shortness of the metatarsals and elongation of the second and third toes. Other radiographic findings were narrowness of the intervertebral disc spaces resulting in precocious degenerative spondylosis and progressive scoliosis. The femoral neck was short and thick and showed a persistent enlargement of the lesser trochanter with a high-riding, bulbous greater trochanter that became more prominent with age. Molecular testing of the diastrophic dysplasia sulfate transporter (DTDST) gene was performed on six patients and no mutations were detected. This radiographic and clinical observation further adds to the evidence that there may be subtypes of DBQD. Long-term follow-up showed that severe precocious osteoarthritis of the hand and spine is a major manifestation of this specific variant. PMID- 20358600 TI - Clinical and molecular characterization of overlapping interstitial Xp21-p22 duplications in two unrelated individuals. AB - Development and implementation of high-density DNA arrays demonstrated the important role of copy number changes on the X chromosome in the etiology of developmental delay and mental retardation (MR). We describe two unrelated patients with developmental delay due to similar interstitial duplications at Xp21-p22. The first patient is a 6-month-old male with multiple affected family members including many females. The second patient is a 5-year-old adopted female. In both patients, chromosome analysis and array comparative genomic hybridization (aCGH) showed duplications of overlapping regions at Xp21-p22. The duplicated segments contain numerous genes associated with MR, including AP1S2, NHS, CDKL5, RPS6KA3, SMS, and ARX. Except for developmental delay, there is little phenotypic overlap between the male and the female patient. Additionally, the female patient and affected female relatives of the male patient have variable severities of cognitive impairment, likely due to different X inactivation patterns and effects of other, nonduplicated genes important for normal development. These cases illustrate that increased gene dosage of X-linked MR genes lead to cognitive impairment. Precise delineation of chromosome rearrangements by aCGH and identification of genes within duplicated segments helped in establishing genotype-phenotype correlations for each of our patients, in comparing them to each other, as well as with previously reported cases of Xp21-p22 duplications. However, we show that even with detailed molecular characterization, phenotype prediction remains challenging in patients with structural abnormalities of the X chromosome. PMID- 20358599 TI - Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. AB - The GALNT3 gene encodes GalNAc-T3, which prevents degradation of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Biallelic mutations in either GALNT3 or FGF23 result in hyperphosphatemic familial tumoral calcinosis or its variant, hyperostosis-hyperphosphatemia syndrome. Tumoral calcinosis is characterized by the presence of ectopic calcifications around major joints, whereas hyperostosis-hyperphosphatemia syndrome is characterized by recurrent long bone lesions with hyperostosis. Here we investigated four patients with hyperphosphatemia and clinical manifestations including tumoral calcinosis and/or hyperostosis-hyperphosphatemia syndrome to determine underlying genetic cause and delineate phenotypic heterogeneity of these disorders. Mutational analysis of FGF23 and GALNT3 in these patients revealed novel homozygous mutations in GALNT3. Although the presence of massive calcifications, cortical hyperostosis, or dental anomalies was not shared by all patients, all had persistent hyperphosphatemia. Three of the patients also had inappropriately normal 1,25-dihyroxyvitamin D [1,25(OH)(2)D] and confirmed low circulating intact FGF23 concentrations. The four novel GALNT3 mutations invariably resulted in hyperphosphatemia as a result of low intact FGF23, but other clinical manifestations were variable. Therefore, tumoral calcinosis and hyperostosis-hyperphosphatemia syndrome represent a continuous spectrum of the same disease caused by increased phosphate levels, rather than two distinct disorders. PMID- 20358598 TI - Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3. AB - Biliary atresia (BA) is a progressive, idiopathic obliteration of the extrahepatic biliary system occurring exclusively in the neonatal period. It is the most common disease leading to liver transplantation in children. The etiology of BA is unknown, although infectious, immune and genetic causes have been suggested. Although the recurrence of BA in families is not common, there are more than 30 multiplex families reported and an underlying genetic susceptibility has been hypothesized. We screened a cohort of 35 BA patients for genomic alterations that might confer susceptibility to BA. DNA was genotyped on the Illumina Human Hap 550 Beadchip platform, which analyzes over 550,000 single nucleotide polymorphisms (SNPs) for genomic deletions and duplications. Areas of increased and decreased copy number were compared to those found in control populations. To identify regions that could serve as susceptibility factors for BA, we searched for regions that were found in BA patients, but not in controls. We identified two unrelated BA patients with overlapping heterozygous deletions of 2q37.3. Patient 1 had a 1.76 Mb (280 SNP), heterozygous deletion containing 30 genes. Patient 2 had a 5.87 Mb (1,346 SNP) heterozygous deletion containing 55 genes. The overlapping 1.76 Mb deletion on chromosome 2q37.3 from 240,936,900 to 242,692,820 constitutes the critical region and the genes within this region could be candidates for susceptibility to BA. PMID- 20358601 TI - A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect. AB - Using an Affymetrix GeneChip(R) Human Mapping 100K Set to study a patient with a late-presenting, right-sided diaphragmatic hernia and microphthalmia, we found a maternally inherited deletion that was 2.7 Mb in size at chromosome 18q22.1. Mapping of this deletion using fluorescence in situ hybridization revealed three deleted genes-CDH19, DSEL, and TXNDC10, and one gene that contained the deletion breakpoint, CCDC102B. We selected DSEL for further study in 125 patients with diaphragmatic hernias, as it is involved in the synthesis of decorin, a protein that is required for normal collagen formation and that is upregulated during myogenesis. We found p.Met14Ile in an unrelated patient with a late-presenting, anterior diaphragmatic hernia. In the murine diaphragm, Dsel was only weakly expressed at the time of diaphragm closure and its expression in C2C12 myoblast cells did not change significantly during myoblast differentiation, thus reducing the likelihood that the gene is involved in myogenesis of the diaphragm. Although it is possible that the 18q22.1 deletion and haploinsufficiency for DSEL contributed to the diaphragmatic defect in the patient, a definite role for DSEL and decorin in the formation of the collagen-containing, central tendon of the diaphragm has not yet been established. PMID- 20358603 TI - Fetal intracranial calcification: pseudo-TORCH phenotype and discussion of related phenotypes. AB - Fetal intracranial calcification (ICC) noted during antenatal imaging poses a diagnostic challenge. Although this presentation is most commonly associated with intrauterine infection, non-infectious causes of fetal ICC have been reported and include metabolic, genetic, or hemodynamic conditions. We report on a patient with antenatally detected extensive ICC, in whom postnatal imaging revealed a distinctive band-like ICC with abnormal gyral pattern and a negative serology for TORCH infections. Such a constellation of findings have been previously described under the terminology of "pseudo-TORCH phenotype," and we posit that our patient represents this entity. Our patient had unreported dysmorphic features, which expands the phenotypic spectrum of this recently described heterogenous condition. In addition we report on the progression of the phenotype both clinically and radiologically. In view of the limited information available for the differential diagnosis of fetal ICC, we also review the available literature on this topic. PMID- 20358602 TI - Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome. AB - Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes (NIPBL, SMC1A, and SMC3) of the cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations in NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex. PMID- 20358604 TI - Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. AB - We report on two siblings doubly heterozygous for null mutations in the recently identified AGS5 gene SAMHD1. The older female child showed mild intellectual disability with microcephaly. Her brother demonstrated a significant spastic paraparesis with normal intellect and head size. Both children had an unclassified chronic inflammatory skin condition with chilblains, and recurrent mouth ulcers. One child had a chronic progressive deforming arthropathy of the small and large joints, with secondary contractures. This family illustrate the remarkable phenotypic diversity accruing from mutations in genes associated with Aicardi-Goutieres syndrome (AGS). The association of arthropathy with SAMHD1 mutations highlights a phenotypic overlap of AGS with familial autoinflammatory disorders such as chronic infantile neurological cutaneous and articular syndrome (CINCA). This family therefore illustrate the need to consider mutation analysis of SAMHD1 in non-specific inflammatory phenotypes of childhood. We propose that arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutieres syndrome because of SAMHD1 mutations. PMID- 20358605 TI - New subtype of familial intracranial calcification in a mother and two children. AB - We report on a mother and two children from a consanguineous Arab Qatari family demonstrating a highly distinctive pattern of intracranial calcification involving the globus pallidus, posterior limb of the internal capsule, genu of the corpus callosum, and deep white matter. Both siblings, a girl and boy, presented with neonatal seizures without subsequent deterioration in neurological function. The girl demonstrated mild to moderate psychomotor delay but her brother and mother showed completely normal development. All three affected individuals were normocephalic. To the best of our knowledge this phenotype represents a novel disorder of inherited brain calcification, which may be recognizable on computerized tomography brain imaging in other cases. Although the disease shows apparent autosomal dominant inheritance, the high degree of consanguinity in the family leaves open the possibility of pseudo-dominance for an autosomal recessive trait. PMID- 20358606 TI - A second patient with Tsukahara syndrome: type A1 brachydactyly, short stature, hearing loss, microcephaly, mental retardation and ptosis. AB - In 1989, Tsukahara and colleagues described a single female with a provisionally unique pattern of malformation consisting of low intelligence, short stature, brachydactyly type A1, and characteristic facial features. We report on a second patient confirming Tsukahara syndrome as an established entity. PMID- 20358607 TI - Microdeletion of the Down syndrome critical region at 21q22. AB - The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice. PMID- 20358608 TI - Periventricular nodular heterotopia and distal limb deficiency: a recurrent association. AB - Malformations of cerebral cortical development, in particular periventricular nodular heterotopia (PNH), and distal transverse limb deficiency have been reported as associated congenital anomalies. Patients with PNH and transverse limb deficiency can be classified as having amniotic band sequence or Adams Oliver syndrome (AOS). Controversy exists whether these should be considered separate entities. In some AOS patients, autosomal recessive inheritance has been shown, but in most patients causes are unknown, and both environmental and genetic factors have been implicated. We present three patients with PNH and distal transverse limb deficiency to support the hypothesis that these should be considered part of one group of disorders, and highlight the variable severity of the clinical and neuroradiological phenotype. Chromosome abnormalities were excluded by copy number analysis on 250K SNP microarray data.Research done on limb deficiency as on PNH caused by mutations in known genes, suggests the involvement of vascular developmental pathways. The combination of limb deficiency and PNH may have a common causative mechanism. Recognition and grouping of patients with this combination of abnormalities will help elucidating the cause. PMID- 20358609 TI - Majewski osteodysplastic primordial dwarfism type II (MOPD II): expanding the vascular phenotype. AB - Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present. PMID- 20358610 TI - A recurrence of a hydrop lethal skeletal dysplasia showing similarity to Desbuquois dysplasia and a proposed new sign: the Upsilon sign. AB - We report on a recurrence of a lethal skeletal dysplasia with features similar to Desbuquois dysplasia (DD) to expand the phenotypic spectrum of DD-like conditions, to increase awareness of DD-like phenotypes in the differential diagnosis of prenatal onset skeletal dysplasias, and to suggest a new sign, the Upsilon sign, to aid in the differential diagnosis of skeletal dysplasias with an extra ossification centre distal to second metacarpal. PMID- 20358611 TI - Lipedema: an inherited condition. AB - Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas. PMID- 20358612 TI - Longitudinal observation of a patient with Rieger syndrome and interstitial deletion 4 (q25-q31.1). AB - Rieger syndrome (RS; OMIM 180500) is a rare autosomal dominant disorder of morphogenesis, with ocular and systemic abnormalities and variability in phenotypic expression. Some patients with RS presented with a deletion of the band 4q25 to which the homeobox gene PIT X2 (former RIEG) was mapped. To study the natural history and perform a genotype-phenotype correlation, we followed a girl with RS from the age of 1 year to puberty. The study included physical examination, clinical and psychological evaluation, and cytogenetic analysis with GTG-banded karyotype and array CGH. Additionally, molecular analysis using microsatellite markers for chromosome 4 (D4S427, D4S194 and D4S1615) was performed. Conventional chromosome analysis showed a 4q deletion, and aCGH confirmed the determination of the breakpoints at 4q25 and 4q31. With the exception of the typical features of RS is the patient, the clinical manifestations were relatively mild, despite the relatively large size of the deleted chromosome segment. The patient was periodically re-evaluated for several years. The teeth are still abnormal, and she is still under orthodontic treatment. The facial features were attenuated with age. Currently, she is under constant monitoring of eye pressure. She benefited from early intervention program, and her tonus is normal. She attends a normal school with minor learning difficulties. In conclusion, this study offers a comprehensive phenotypic delineation of RS through almost two decades and may contribute to a more accurate genetic counseling in cases of this syndrome. PMID- 20358613 TI - RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome. AB - We report here on a RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome. All children presented with acrocephaly and polysyndactyly. However, intrafamilial variability was observed with variable severity of craniosynostosis ranging from cloverleaf skull to predominant involvement of the metopic ridge. All children also presented with a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly (2/4) in the hands, and preaxial polydactyly (3) and syndactyly (4) in the toes. Mental development was normal in all four children but the eldest one presented with impaired motor development as a result of orthopedic complications. Brain imaging showed hydrocephalus in 2/4 and additional features included genu valgum (2/4), abnormal genitalia (3/4), corneal anomaly (2/4), umbilical hernia (1/4), severe cyphoscoliosis (1), patent ductus arteriosus (1/4), and accessory spleen (1). In contrast to previous reports, growth was below average except for one patient and the eldest one became moderately overweight with time. We conclude from the report of this large unique family with four affected children that Carpenter syndrome is a genetically homogenous but a clinically variable condition. PMID- 20358614 TI - Interstitial deletion 1q42 in a patient with agenesis of corpus callosum: Phenotype-genotype comparison to the 1q41q42 microdeletion suggests a contiguous 1q4 syndrome. AB - Interstitial deletions of 1q4 are rare and present with different deletion breakpoints and variable phenotype. We report on the clinical and molecular cytogenetic findings in a girl with minor anomalies, midline defects including prenatally ascertained agenesis of the corpus callosum, epilepsy and developmental delay. A de novo 5.45 Mb deletion almost exclusively located within 1q42 was found to cause this phenotype, which shows significant overlap with the microdeletion 1q41q42 syndrome reported in a few patients except for the agenesis of the corpus callosum. However, deletions in patients with the 1q41q42 syndrome mainly extend into the 1q41 region with a region of overlap including the DISP1 gene involved in the SHH pathway, which is not part of the 1q42 deletion in our patient. We suggest that an interaction of genes involved in pathways of embryonic development rather than haploinsufficiency of single genes in the so called critical regions is causing complex malformation syndromes due to cytogenetic microaberrations in the 1q4 region. PMID- 20358615 TI - Additional clinical and molecular analyses of TFAP2A in patients with the branchio-oculo-facial syndrome. AB - The branchio-oculo-facial syndrome (BOFS) is a rare disorder with approximately 50 sporadic and familial cases in the literature. We report on the clinical and molecular analyses of five additional patients with BOFS (two familial and three sporadic). DNA analysis of the TFAP2A gene associated with BOFS using DNA sequencing detected a mutation [c.763A>G (p.Arg255Gly)] in two unrelated patients. This mutation had been reported in another patient and indicates a probable mutational hotspot in the TFAP2A gene. We also detected three new mutations which are restricted to exons 4-6. These gene regions are almost free of any single nucleotide polymorphisms. An evolutionary sequence comparison showed a high degree of sequence conservation from humans to the honey bee (Apis mellifera) in exon 6 showing that this part of the protein is probably essential. Our study represents the second group of BOFS patients with molecular confirmation, expanding the phenotype and spectrum of mutations and limiting it to a restricted part of the gene. PMID- 20358616 TI - A tale of two deletions: a report of two novel 20p13 --> pter deletions. AB - We report on two patients with 1.7 and 1.2 Mb terminal 20p deletions, which have apparently not been reported previously. Both individuals exhibit certain similar features including large fontanelles, ear abnormalities, and seizures. However, even though the deletions are of similar size, there were many disparate features between the two. The deletions in each patient encompass at least 28 genes that may provide useful candidates for ear development and cranial ossification. PMID- 20358617 TI - Characterization of an interstitial 4q32 deletion in a patient with mental retardation and a complex chromosome rearrangement. AB - Interstitial deletions of chromosome band 4q32 are rare. We report on a 22-year old female patient with a de novo interstitial deletion of chromosome 4q32 and a balanced translocation t(2;5)(p21;q12.1). Clinical problems of the patient comprised mild to moderate mental retardation, psychosis, obesity, broad nasal root, sparse lateral eyebrows, thin upper lip, short philtrum, micrognathia, and strabismus. Analysis by whole genome array CGH using an Agilent 244K oligonucleotide array and subsequent FISH using BAC clones from the 4q32 region revealed an unexpectedly complex rearrangement comprising a deletion of approximately 10 Mb in 4q32.1q32.3 and the insertion of two small fragments of 0.8 and 0.11 Mb originating from the derivative chromosome 4q32 into derivative chromosome 5q. The breakpoints of the t(2;5) translocation were mapped by BAC FISH; no genes were disrupted by these breakpoints. The deleted interval in 4q32 harbored more than 30 genes, and haploinsufficiency of one or several of these genes is likely to have caused the clinical problems of the patient. Candidate genes for cognitive defects are GRIA2, GLRB, NPY1R, and NPY5R. In conclusion, this patient increases our knowledge about the phenotypic consequences of interstitial 4q32 deletions. Reports of patients with overlapping deletions will be needed to elucidate the role of individual genes and to establish genotype phenotype correlations. PMID- 20358618 TI - Further delineation of the Kapur-Toriello syndrome. AB - The Kapur-Toriello syndrome (KTS) is a rare multiple congenital anomaly syndrome, with presumed autosomal recessive inheritance based on the initial report of affected siblings. Here we report on a female with multiple anomalies, including cleft lip and palate, coloboma, mental retardation with cerebral atrophy, and imperforate anus who, upon re-evaluation at 30 months, was recognized to have a columella that extended below the nares. This distinctive finding prompted the diagnosis of KTS. This is the 5th report of KTS, and the second female. Interestingly, both female cases also manifest an ano/rectal malformation, suggesting that this should be considered a component manifestation of this rare syndrome. PMID- 20358619 TI - Germline TGF-beta receptor mutations and skeletal fragility: a report on two patients with Loeys-Dietz syndrome. AB - Loeys-Dietz syndrome (LDS, OMIM # 609192) caused by heterozygous mutations in TGFBR1 and TGFBR2 has recently been described as an important cause of familial aortic aneurysms. These patients have craniofacial and skeletal features that overlap with the Marfan syndrome (MFS), and more importantly, have significant vascular fragility as is seen in MFS and Ehlers-Danlos syndrome Type IV (EDS-IV). The skeletal phenotype with respect to low bone mineral density and skeletal fragility is not clear. We present two patients with LDS with significant skeletal fragility. The first is a 17-year-old male who had talipes equinovarus, diaphragmatic and inguinal and herniae, aortic root dilatation necessitating surgical repair, craniofacial and skeletal dysmorphism consistent with LDS, and a history of numerous fragility fractures leading to significant skeletal deformity. He was found to be heterozygous for a c.923T > C transition in exon 4 of TGFBR2. The second is a 26-year-old male with submucous cleft palate, talipes equinovarus, pectus excavatum requiring surgery, inguinal hernia, and aneurysms in the ascending aorta, abdominal aorta, carotid, subclavian, vertebral and brachial arteries requiring surgical repairs. He also had craniofacial and skeletal dysmorphism consistent with LDS, multiple fractures in childhood, low bone mineral density, and was found to be heterozygous for a c.1561 T > C transition in exon 7 of TGFBR2. These case studies highlight the importance of paying close attention to fractures and bone density in patients with LDS. Osteopenia or osteoporosis may become increasingly important issues as earlier detection and treatment of the vascular complications of LDS improves life expectancy in these patients. PMID- 20358620 TI - Severe pulmonary emphysema in a girl with interstitial deletion of 2q24.2q24.3 including ITGB6. AB - Owing to the large size of chromosome 2, partial monosomy of the long arm of this chromosome gives rise to many specific phenotypes. We report on a 2-month-old girl with an interstitial deletion of 2q24.2q24.3, which was confirmed by microarray-based comparative genomic hybridization analysis. The patient showed delayed growth and mental retardation, early myoclonic seizures, and characteristic dysmorphic features including thick arched eyebrows, upslanting palpebral fissures, long eyelashes, depressed nasal bridge, short nose, long philtrum, small mouth, micrognathia, and low set ears. Her early myoclonic seizures were likely due to haploinsufficiency of SCN1A and SCN2A, which are included in the deletion region. When she experienced acute bronchopneumonia, she showed severe pulmonary emphysema. The deletion region of 2q24.2 includes the integrin beta6 gene (ITGB6), which may prevent acute lung injury and pulmonary emphysema. Many previously reported patients with deletions of 2q24.2 showed poor outcomes because of respiratory failure. These observations suggest the possibility of a strong relationship between haploinsufficiency of ITGB6 and pulmonary dysfunction. PMID- 20358621 TI - Interstitial microdeletion of 4p16.3: contribution of WHSC1 haploinsufficiency to the pathogenesis of developmental delay in Wolf-Hirschhorn syndrome. PMID- 20358622 TI - Transverse limb defect in a patient with Jacobsen syndrome: concurrence of malformation and disruption. PMID- 20358623 TI - Rubinstein-Taybi syndrome in first cousins with different de novo mutations. PMID- 20358624 TI - A patient with Duchenne muscular dystrophy and autism demonstrates a hemizygous deletion affecting Dystrophin. PMID- 20358625 TI - A tandem duplication of chromosome 21 in a newborn showing a phenotype inconsistent with Down syndrome. PMID- 20358626 TI - 18q22.3 --> 18q23 deletion syndrome and cleft palate. PMID- 20358627 TI - Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings. AB - Pseudoxanthoma elasticum (PXE) is a systemic disorder affecting elastic tissues most markedly in skin, retina, and blood vessels. It is caused by mutations in the ABCC6 gene and is transmitted in an autosomal recessive fashion. In 1994 a new classification system for PXE was published as the result of a consensus conference. Since then the ABCC6 gene has been discovered. We propose that there is a need for a classification system incorporating all relevant systemic symptoms and signs, based on standardized clinical, histological, and molecular biological examination techniques. We re-evaluated the histopathologic PXE signs and propose a classification system with unambiguous criteria leading to a consistent diagnosis of definitive, probable, or possible PXE world-wide. We put this proposed classification forward to encourage further debate on the diagnosis of this multi-organ disorder. PMID- 20358628 TI - 3p Deletion and (skewed) literature review. PMID- 20358631 TI - KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: implication for combinatorial approach. AB - KRAS is frequently mutated in nonsmall cell lung cancer (NSCLC), resulting in the activation of the MAPK/ERK kinase (MEK)/ERK pathway. High-throughput mutation profile has shown that lung cancer frequently harbors comutation of cancer related genes. Therefore, given that cancer cells have multiple genetic alterations, combinatorial therapeutic strategy is demanded for effective cancer therapy. To address this, we first characterized MEK dependence in four NSCLC cells. Two cells (H358, A549) carried KRAS mutation only, and the other two (H23, H157) harbored comutation of KRAS/PTEN. H358 cells with KRAS mutation only were sensitive to MEK inhibition. However, the other KRAS mutant A549 cells were resistant to MEK inhibition. Previously, we have shown that dual inhibition of EGFR and MEK signaling shows a synergistic effect on KRAS mutant gastric cancer cells by suppressing compensatory activation of AKT. Here we also observed that this combination was effective in KRAS mutant A549 cells. However, the combination was ineffective in H23 and 157 cells with comutation of KRAS/PTEN. Compared to KRAS mutant/PTEN wild-type cells, signal transducer and activator of transcription 3 (STAT3) was significantly activated following MEK inhibition in KRAS/PTEN comutant cells. Combined STAT3 inhibition by a JAK2 inhibitor or gene knockdown with MEK inhibition blocked STAT3 activation, synergistically suppressed cell growth, and induced apoptosis in comutant cells. Taken together, our study provides molecular insights that help explain the heterogeneous response to MEK inhibition in KRAS mutant lung cancers, and presents a rationale for the clinical investigation of combination of MEK and EGFR inhibitor or MEK and JAK2 inhibitor depending on PTEN status. PMID- 20358633 TI - HILIC and mixed-mode chromatography: the rising stars in separation science. PMID- 20358632 TI - LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinoma. AB - BACKGROUND: LAPTM4B-35 is a 35-kDa tetra-transmembrane protein overexpressed in hepatocellular carcinoma (HCC) and promotes cell survival, proliferation, and tumorigenesis. However, the potential clinical implications of LAPTM4B-35 in HCC are still unclear. This study is aimed to investigate the correlations between LAPTM4B-35 expression and prognosis in patients with HCC. METHODS: Western blot and immunohistochemistry assays were used to determine the expression of LAPTM4B 35 in HCCs and their paired noncancerous liver tissues from 65 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters were assessed by Chi-square test. Patient survival was determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. RESULTS: LAPTM4B-35 overexpression occurred in 76.9% of HCC tissues, while only in 4.6% of noncancerous liver tissues. Overexpression of LAPTM4B-35 was significantly associated with TNM staging and invasive tumors. Patients with higher LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P < 0.001). On multivariate analysis, elevated expression of LAPTM4B-35 was found to be an independent prognostic factor for OS and DFS (P = 0.009, 0.043, respectively). CONCLUSIONS: LAPTM4B-35 overexpression is an independent prognostic factor for OS and DFS of HCC. PMID- 20358635 TI - Proceedings from the Cleveland Clinic Workshop on Innovation in Treatment of Uremia. PMID- 20358636 TI - ICPF Cleft 2008. Proceedings from the International Cleft Palate Conference, Dallas, Texas, USA. PMID- 20358634 TI - Flexible UV-ozone-modified carbon nanotube electrodes for neuronal recording. PMID- 20358637 TI - Exterminated by the bloody flux: dysentery in eighteenth-century naval and military medical accounts. PMID- 20358639 TI - Laying the foundation for catalytic change. Interview by Susan Dentzer. PMID- 20358638 TI - Surgical site infections in HIV-infected patients: results from an Italian prospective multicenter observational study. AB - BACKGROUND: The quality of life of the HIV-infected population in developed countries has substantially improved over the years. Accordingly, the clinical limitations in the surgical treatment of the HIV-infected patients are becoming fewer, and the number of HIV-infected patients undergoing surgical interventions of all types is increasing. However, available data on the incidence and risk factors for post-surgical complications, such as surgical site infections (SSI), in HIV-infected patients are still limited and often controversial. The aim of this study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients. METHODS: A 1-year observational prospective multicenter surveillance study was conducted in 11 Italian Infectious Diseases Clinical Centers from which 305 consecutive HIV-infected patients undergoing different surgical procedures were enrolled. Postdischarge surveillance was conducted within 30 days after surgery. A number of variables were included in a multivariate analysis aimed at assessing potential risk factors for SSI, including body mass index, diabetes, Hepatitis C (HCV) and hepatitis B virus infection, lipodistrophy, HIV viral load, CD4 cell count and white blood cell count, preoperative hospital stay, National Nosocomial Infection Surveillance (NNIS) risk score, and any antimicrobial prophylaxis. RESULTS: SSI occurred in 29 of 305 (9.5%) patients, of which 17 (58.6%) SSI occurred during hospital stay, and 12 (41.4%) occurred during the postdischarge period. The SSI of the 29 patients were classified as superficial (21, 72.4%), deep (four, 13.8%), organ/space (one, 3.4%), and sepsis (three, 10.3%). Nearly 50% of the superficial and 50% of the deep SSI occurred during the postdischarge period. Organ/space infection and sepsis accounted for 13.7% of all SSI and were observed during the in-hospital stay. The multivariate analysis revealed that HCV co-infection was significantly associated to SSI occurrence. Total hospital stay was longer among patients with SSI than among those without SSI (p = 0.041). CONCLUSION: Although 92.5% of our HIV-infected patients presented a NNIS score < or = 1, the SSI rate was twofold higher than that reported in Italian and European studies for the general population, with more severe clinical presentations. This is the first report of an association between HCV-HIV co-infection and SSI occurrence. Additionally, the viro-immunological status of our patients was not related to SSI occurrence, which suggests the need for further research for other potential risk factors that may be implicated in the occurrence of SSI. PMID- 20358640 TI - Reversible lesion in the splenium of the corpus callosum in a child with influenza-associated encephalitis-encephalopathy (IAEE). PMID- 20358641 TI - Cell culture platform with mechanical conditioning and nondamaging cellular detachment. AB - Cells implanted after injury may remodel undesirably with improper mechanical stimulation from surrounding tissue. Proper conditioning of tissue engineered constructs before implantation can lead to suitable tissue architectures, along with an extracellular matrix (ECM) environment that more closely mimics native tissue. Additionally, cell implantation without bulky polymeric scaffolding is often desirable. Previous researchers have created devices capable of applying mechanical forces to cells (e.g., stretch) but cellular removal from these devices, such as by trypsin, often results in irreversible damage. Conversely, devices are available that can detach intact cells, but these are inelastic, nonstretchable substrates. We have created a cell culture platform that allows for mechanical conditioning and then subsequent nondamaging detachment of those cells. We have modified silicone culture surfaces, to incorporate thermally responsive polymers of N-isopropylacrylamide (NIPAAm) to create an elastic substrate that can also change surface properties with temperature change. A copolymer of NIPAAm and 10percent w/w acrylic acid (AAc) was conjugated to an amine-bonded silicone surface through carbodiimide chemistry. Cells were able to attach to the resulting surfaces at 37 degreeC and showed detachment by rounded morphology at 25degreeC. Following mechanical stretching, cells were still able to spontaneously detach from these modified silicone surfaces with temperature change. PMID- 20358642 TI - Proposed nurse license fee increase to help solve Oregon nursing shortage. PMID- 20358643 TI - Proceedings of the International Conference on Biorefinery and the 5th International Conference on Separation Science and Technology, October 20-23, 2007, Beijing, China. PMID- 20358645 TI - Sphenoid wing lesion. PMID- 20358646 TI - [Acute myocardial infarction due to thrombosis after withdrawal of antiplatelet treatment in a patient with a drug-releasing stent]. PMID- 20358647 TI - [Anaphylaxis and adjuvants]. PMID- 20358644 TI - The RON tyrosine kinase receptor regulates vascular endothelial growth factor production in pancreatic cancer cells. AB - OBJECTIVES: The RON receptor mediates tumorigenic phenotypes in pancreatic cancer (PC), but no investigations currently have implicated RON signaling as a regulator of angiogenesis in PC. Angiogenesis is vital to oncogenesis, and vascular endothelial growth factor (VEGF) is the most well-characterized angiogenic protein. This study sought to determine the effect of RON stimulation on in vitro angiogenesis and VEGF production in PC cell lines. METHODS: Vascular endothelial growth factor levels from conditioned media of hepatocyte growth factor-like protein-stimulated BxPC-3 and FG cells were quantitated via enzyme linked immunosorbent assay and likewise interrogated in the presence and absence of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase/AKT inhibitors. To determine in vitro angiogenesis, human microvascular endothelial cells were subsequently exposed to the same conditioned media to assay for microtubule formation. RESULTS: RON signaling resulted in a 52% and 34% increase in VEGF levels in BxPC-3 and FG cells, respectively. Vascular endothelial growth factor secretion was inhibited with MAPK or phosphatidylinositol-3-kinase blockade in BxPC-3 cells, but only MAPK inhibition resulted in decreased VEGF production in FG cells. BxPC-3 conditioned media induced tubule formation in human microvascular endothelial cells, which was abrogated by RON inhibition. CONCLUSIONS: RON signaling results in MAPK-mediated VEGF secretion by PC cells and promotion of microtubule formation. These findings suggest another mechanism by which RON signaling may promote PC progression. PMID- 20358648 TI - Further evidence for the spread of attention during contour grouping: a reply to Crundall, Dewhurst, and Underwood (2008). AB - In a contour-grouping task, subjects decide whether contour elements belong to the same or different curves. Houtkamp, Spekreijse, and Roelfsema (2003) demonstrated that object-based attention spreads gradually over contour elements that have to be grouped in perception. Crundall, Dewhurst, and Underwood (2008) challenged this spreading-attention model and suggested that attention in the contour-grouping task is not object based but rather has the shape of a zoom lens that moves along the relevant curve. To distinguish between object-based and spatial attention, they changed the stimulus and measured the impact on performance. Subjects were not able to correct for changes at the start of the relevant curve toward the end of the trial. They suggested that attention did not stay at the beginning of the curve, in accordance with a moving zoom lens model. Here, we examine the task of Crundall et al. and find that subjects perceive the changes but fail to correct their response. By measuring change detection directly, we find that performance is much better for the start of the relevant curve than for an irrelevant curve, at all times. Our findings do not support the zoom lens model but provide further support for the spreading attention model. PMID- 20358649 TI - Structure and function of the vertebrate magnetic sense. AB - Some vertebrates can navigate over long distances using the Earth's magnetic field, but the sensory system that they use to do so has remained a mystery. Here we describe the key components of a magnetic sense underpinning this navigational ability in a single species, the rainbow trout (Oncorhynchus mykiss). We report behavioural and electrophysiological responses to magnetic fields and identify an area in the nose of the trout where candidate magnetoreceptor cells are located. We have tracked the sensory pathway from these newly identified candidate magnetoreceptor cells to the brain and associated the system with a learned response to magnetic fields. PMID- 20358650 TI - ["Can there be no exceptional status for exceptional people?" The law on registered partnership: its history and implications]. PMID- 20358651 TI - ["The marital duty that a husband owes his wife": love, masculinity, and the bed in Swedish marriage ideology, ca. 1760-1835]. PMID- 20358652 TI - Partners in crime: diabetes & obesity. PMID- 20358653 TI - Most reliable condoms. PMID- 20358654 TI - Concern over canned foods. Our tests find wide range of bisphenol A in soups, juice, and more. PMID- 20358655 TI - Is it a cold or the flu? PMID- 20358656 TI - [The cemeteries of the "Turkish slaves" of the arsenals of Marseilles and Toulouse during the 18th century]. PMID- 20358657 TI - Information from your doctor. MRSA: What you should know. PMID- 20358658 TI - Information from your family doctor. Urethritis in men. PMID- 20358659 TI - Legal ephedra? PMID- 20358660 TI - Will a pill boost your brain power? PMID- 20358661 TI - Revisiting the great famine. PMID- 20358662 TI - Deadly infections. Hospitals can lower the risks, but many fail to act. PMID- 20358663 TI - Homes for the working class? Irish public house-building cycles, 1945-2001. PMID- 20358664 TI - [Exercises, physical activities and public health (21). Exercises, physical activities, stress and mental health]. PMID- 20358665 TI - [Revision of the law concerning public health nurses, midwives and nurses and an overview on public health nursing education (5). The educational system for the educational course for public health nurses]. PMID- 20358666 TI - ["No longer normal but still not mentally ill": cases of borderline psychopathology in imperial Germany]. PMID- 20358667 TI - [The pious insane and psychiatry in the Vormarz period: religious madness among patients at the Hofheim hospital in the grand duchy of Hesse]. PMID- 20358668 TI - ["Bringing sandwich consumption into line": the psychology of nutrition in the Third Reich - two source texts]. PMID- 20358670 TI - [Witches, learned discourse, and discipline: magic and the early Enlightenment in the Saxon Ore Mountains, 1712-20]. PMID- 20358671 TI - [The spirit of self-reliance and the appropriation of Western science: the transition in Chinese literati attitudes toward Western science and its social context, ca. 1700-60]. PMID- 20358672 TI - [A Chinese translation of Ambroise Pare's Anatomie]. PMID- 20358673 TI - The vest. PMID- 20358674 TI - Article focuses on often-ignored male breast cancer. PMID- 20358675 TI - Invisible and involuntary: female genital mutilation as a basis for asylum. PMID- 20358676 TI - Well-being of the elderly residing in old age home vs. those in family setting in Tripura. PMID- 20358677 TI - Immediate effects of effleurage back massage on physiological and psychological relaxation. PMID- 20358678 TI - Computer vision syndrome. PMID- 20358679 TI - Molecular, clinical and environmental toxicology. Volume 2: clinical toxicology. Preface. PMID- 20358681 TI - Toxicology of mycotoxins. AB - Humans are exposed to mycotoxins via ingestion, contact and inhalation. This must have occurred throughout human history and led to severe outbreaks. Potential diseases range from akakabio-byo to stachybotryotoxicosis and cancer. The known molecular bases of toxicology run the gamut of 23 compounds, from aflatoxins (AFs) to zearalenone, ochratoxin A and deoxynivalenol. Ergotism is one of the oldest recognized mycotoxicosis, although mycotoxin science only commenced in the 1960s with the discovery of AFs in turkey feed. AFs are carcinogenic. Some others are suspected carcinogens. The effects of mycotoxins are acute or chronic in nature. Mycotoxins are well known in the scientific community, although they have a low profile in the general population. An incongruous situation occurs in United States where mycotoxins from "moldy homes" are considered to be a significant problem, although there is a general debate about seriousness. This contrasts with the thousands of deaths from mycotoxins that occur, even now, in the technologically less developed countries (e.g., Indonesia, China, and Africa). Mycotoxins are more toxic than pesticides. Studies are moving from whole animal work to investigating the biochemical mechanisms in isolated cells, and the mechanisms of toxicity at the molecular level are being elucidated. The stereochemical nature of AFs has been shown to be important. In addition, the effect of multiple mycotoxins is being increasingly investigated, which will more accurately represent the situation in nature. It is anticipated that more fungal metabolites will be recognized as dangerous toxins and permitted statutory levels will decrease in the future. PMID- 20358682 TI - Phycotoxins: chemistry, mechanisms of action and shellfish poisoning. AB - Phycotoxins are natural metabolites produced by micro-algae. Through accumulation in the food chain, these toxins may concentrate in different marine organisms, including filter-feeding bivalves, burrowing and grazing organisms, herbivorous and predatory fish. Human poisoning due to ingestion of seafood contaminated by phycotoxins has occurred in the past, and harmful algal blooms (HABs) are naturally occurring events. Still, we are witnessing a global increase in HABs and seafood contaminations, whose causative factors are only partially understood. Phycotoxins are small to medium-sized natural products and belong to many different groups of chemical compounds. The molecular mass ranges from approximately 300 to over 3000 Da, and the compound classes represented include amino acids, alkaloids and polyketides. Each compound group typically has several main compounds based on the same or similar structure. However, most groups also have several analogues, which are either produced by the algae or through metabolism in fish or shellfish or other marine organisms. The different phycotoxins have distinct molecular mechanisms of action. Saxitoxins, ciguatoxins, brevetoxins, gambierol, palytoxins, domoic acid, and, perhaps, cyclic imines, alter different ion channels and/or pumps at the level of the cell membrane. The normal functioning of neuronal and other excitable tissues is primarily perturbed by these mechanisms, leading to adverse effects in humans. Okadaic acid and related compounds inhibit serine/threonine phosphoprotein phosphatases, and disrupt major mechanisms controlling cellular functions. Pectenotoxins bind to actin filaments, and alter cellular cytoskeleton. The precise mechanisms of action of yessotoxins and azaspiracids, in turn, are still undetermined. The route of human exposure to phycotoxins is usually oral, although living systems may become exposed to phycotoxins through other routes. Based on recorded symptoms, the major poisonings recognized so far include paralytic, neurotoxic, amnesic, diarrheic shellfish poisonings, ciguatera, as well as palytoxin and azaspiracid poisonings. PMID- 20358680 TI - Toxins from bacteria. AB - Bacterial toxins damage the host at the site of bacterial infection or distant from the site. Bacterial toxins can be single proteins or oligomeric protein complexes that are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity. ADP ribosylation of host proteins is the earliest post-translational modification determined to be performed by bacterial toxins; other modifications include glucosylation and proteolysis. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers the A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the secretion mechanism that delivers the toxin out of the bacterium, termed types I-VII. This review summarizes the major families of bacterial toxins and also describes the specific structure-function properties of the botulinum neurotoxins. PMID- 20358683 TI - Poisonous plants. AB - A large number of plants can cause adverse effects when ingested by animals or people. Plant toxicity is due to a wide diversity of chemical toxins that include alkaloids, glycosides, proteins and amino acids. There are several notable toxic plants for which a specific chemical responsible for toxicity has not been determined. There are many examples of species differences in terms of their sensitivity to intoxication from plants. Pets, such as dogs and cats, and people, especially children, are frequently exposed to the same toxic plants due to their shared environments. On the other hand, livestock are exposed to toxic plants that are rarely involved in human intoxications due to the unique environments in which they are kept. Fortunately, adverse effects often do not occur or are generally mild following most toxic plant ingestions and no therapeutic intervention is necessary. However, some plants are extremely toxic and ingestion of small amounts can cause rapid death. The diagnosis of plant intoxication can be challenging, especially in veterinary medicine where a history of exposure to a toxic plant is often lacking. Analytical tests are available to detect some plant toxins, although their diagnostic utility is often limited by test availability and timeliness of results. With a few notable exceptions, antidotes for plant toxins are not available. However, general supportive and symptomatic care often is sufficient to successfully treat a symptomatic patient. PMID- 20358684 TI - Toxic plants: a chemist's perspective. AB - Chemistry has long been an integral part of toxicology, as the two fields originated in much the same way: the investigation of plants with interesting properties. In this chapter I review the role that chemistry has played in understanding toxic and medicinal plants. After some introductory remarks, three broad areas are addressed: the role of natural products in understanding plant taxonomy and evolution, recent developments in chemical synthesis, especially efforts to discover and efficiently synthesize novel structures based upon naturally occurring toxins, and finally, developments in the new field of systems toxicology, which seeks to integrate all aspects of an organism's response to toxic insult. PMID- 20358685 TI - High-molecular weight protein toxins of marine invertebrates and their elaborate modes of action. AB - High-molecular weight protein toxins significantly contribute to envenomations by certain marine invertebrates, e.g., jellyfish and fire corals. Toxic proteins frequently evolved from enzymes meant to be employed primarily for digestive purposes. The cellular intermediates produced by such enzymatic activity, e.g., reactive oxygen species or lysophospholipids, rapidly and effectively mediate cell death by disrupting cellular integrity. Membrane integrity may also be disrupted by pore-forming toxins that do not exert inherent enzymatic activity. When targeted to specific pharmacologically relevant sites in tissues or cells of the natural enemy or prey, toxic enzymes or pore-forming toxins even may provoke fast and severe systemic reactions. Since toxin-encoding genes constitute "hot spots" of molecular evolution, continuous variation and acquirement of new pharmacological properties are guaranteed. This also makes individual properties and specificities of complex proteinaceous venoms highly diverse and inconstant. In the present chapter we portray high-molecular weight constituents of venoms present in box jellyfish, sea anemones, sea hares, fire corals and the crown-of thorns starfish. The focus lies on the latest achievements in the attempt to elucidate their molecular modes of action. PMID- 20358686 TI - Venomous animals: clinical toxinology. AB - Venomous animals occur in numerous phyla and present a great diversity of taxa, toxins, targets, clinical effects and outcomes. Venomous snakes are the most medically significant group globally and may injure >1.25 million humans annually, with up to 100 000 deaths and many more cases with long-term disability. Scorpion sting is the next most important cause of envenoming, but significant morbidity and even deaths occur following envenoming with a wide range of other venomous animals, including spiders, ticks, jellyfish, marine snails, octopuses and fish. Clinical effects vary with species and venom type, including local effects (pain, swelling, sweating, blistering, bleeding, necrosis), general effects (headache, vomiting, abdominal pain, hypertension, hypotension, cardiac arrhythmias and arrest, convulsions, collapse, shock) and specific systemic effects (paralytic neurotoxicity, neuroexcitatory neurotoxicity, myotoxicity, interference with coagulation, haemorrhagic activity, renal toxicity, cardiac toxicity). First aid varies with organism and envenoming type, but few effective first aid methods are recommended, while many inappropriate or frankly dangerous methods are in widespread use. For snakebite, immobilisation of the bitten limb, then the whole patient is the universal method, although pressure immobilisation bandaging is recommended for bites by non-necrotic or haemorrhagic species. Hot water immersion is the most universal method for painful marine stings. Medical treatment includes both general and specific measures, with antivenom being the principal tool in the latter category. However, antivenom is available only for a limited range of species, not for all dangerous species, is in short supply in some areas of highest need, and in many cases, is supported by historical precedent rather than modern controlled trials. PMID- 20358687 TI - Mechanistic insights on spider neurotoxins. AB - In physiology research, animal neurotoxins historically have served as valuable tools for identification, purification, and functional characterization of voltage-dependent ion channels. In particular, toxins from scorpions, sea anemones and cone snails were at the forefront of work aimed at illuminating the three-dimensional architecture of sodium channels. To date, at least six different receptor binding sites have been identified and--most of them- structurally assigned in terms of protein sequence and spatial disposition. Recent work on Australian funnel-web spiders identified certain peptidic ingredients as being responsible for the neurotoxicity of the crude venom. These peptides, termed delta-atracotoxins (delta-ACTX), consist of 42 amino acids and bind to voltage-gated sodium channels in the same way as classical scorpion alpha toxins. According to the 'voltage-sensor trapping model' proposed in the literature, delta-ACTX isoforms interact with the voltage sensor S4 transmembrane segment of alpha-subunit domain IV, thereby preventing its normal outward movement and concurrent conformational changes required for inactivation of the channel. As consequence prolonged action potentials at autonomic or somatic synapses induce massive transmitter release, resulting in clinical correlates of neuroexcitation (e.g., muscle fasciculation, spasms, paresthesia, tachycardia, diaphoresis, etc.). On the other hand, the major neurotoxin isolated from black widow spiders, alpha-latrotoxin (alpha-LTX), represents a 132 kDa protein consisting of a unique N-terminal sequence and a C-terminal part harboring multiple ankyrin-like repeats. Upon binding to one of its specific presynaptic receptors, alpha-LTX has been shown to tetramerize under physiological conditions to form Ca2+-permeable pores in presynaptic membranes. The molecular model worked out during recent years separates two distinguishable receptor-mediated effects. According to current knowledge, binding of the N terminus of alpha-LTX at one of its specific receptors either triggers intracellular signaling cascades, resulting in phospholipase C-mediated mobilization of presynaptic Ca2+ stores, or leads to the formation of tetrameric pore complexes, allowing extracellular Ca2+ to enter the presynaptic terminal. Alpha-LTX-triggered exocytosis and fulminant transmitter release at autonomic synapses may then provoke a clinical syndrome referred to as 'latrodectism', characterized by local and incapacitating pain, diaphoresis, muscle fasciculation, tremor, anxiety, and so forth. The present review aims at providing a short introduction into some of the exciting molecular effects induced by neurotoxins isolated from black widow and funnel-web spiders. PMID- 20358688 TI - Analytical toxicology. AB - This paper reviews procedures for screening, identification and quantification of drugs, poisons and their metabolites in biosamples, and the corresponding work-up procedures. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry are mostly used today in analytical toxicology. Selection of the most appropriate biosample, e.g., ante/postmortem blood, urine, or tissues or alternative matrices like hair, sweat and oral fluid, nails or meconium, is discussed. The importance of quality control and possibilities and limitations of interpretation of the analytical result are also discussed. PMID- 20358689 TI - Household chemicals: management of intoxication and antidotes. AB - Exposure to household products is very common, but in industrialized countries severe or fatal poisoning with household products is rare today, due to the legal restriction of sale of hazardous household products. The big challenge for physicians, pharmacologists and toxicologists is to identify the few exceptional life-threatening situations where immediate intervention is needed. Among thousands of innocuous products available for the household only very few are hazardous. Substances found in these products include detergents, corrosives, alcohols, hydrocarbons, and some of the essential oils. The ingestion of batteries and magnets and the exposure to cyanoacrylates (super glue) can cause complications in exceptional situations. Among the most dangerous substances still present in household products are ethylene glycol and methanol. These substances cause major toxicity only through their metabolites. Therefore, initial symptoms may be only mild or absent. Treatment even in asymptomatic patients has to be initiated as early as possible to inhibit production of toxic metabolites. For all substances not only the compound itself but also the route of exposure is relevant for toxicity. Oral ingestion and inhalation generally lead to most pronounced symptoms, while dermal exposure is often limited to mild irritation. However, certain circumstances need special attention. Exposure to hydrofluoric acid may lead to fatal hypocalcemia, depending on the concentration, duration of exposure, and area of the affected skin. Accidents with hydrocarbon pressure injectors and spray guns are very serious events, which may lead to amputation of affected limbs. Button batteries normally pass the gastrointestinal tract without problems even in toddlers; in rare cases, however, they get lodged in the esophagus with the risk of localized tissue damage and esophageal perforation. PMID- 20358690 TI - Heavy metal poisoning: management of intoxication and antidotes. AB - Of the known elements, nearly 80% are either metals or metalloids. The highly reactive nature of most metals result in their forming complexes with other compounds such oxygen, sulfide and chloride. Although this reactivity is the primary means by which they are toxic, many metals, in trace amounts, are vital to normal physiological processes; examples include iron in oxygen transport, manganese and selenium in antioxidant defense and zinc in metabolism. With these essential metals toxicity occurs when concentrations are either too low or too high. For some metals there are no physiological concentrations that are beneficial; as such these metals only have the potential to cause toxicity. This chapter focuses on four of these: arsenic, mercury, lead and thallium. PMID- 20358691 TI - Drugs and pharmaceuticals: management of intoxication and antidotes. AB - The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life support- airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N acetylcysteine, physostigmine, L-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of decontamination and enhanced elimination, and the use of specific antidotes where warranted. Data supporting antidotes effectiveness vary considerably. Clinicians are encouraged to utilize consultation with regional poison centers or those with toxicology training to assist with diagnosis, management, and administration of antidotes, particularly in unfamiliar cases. PMID- 20358692 TI - Inhalation toxicology. AB - Inhalation of gases, vapors and aerosols can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. The large number of chemicals and complex mixtures present in indoor and outdoor air coupled with the introduction of new materials such as nanoparticles and nanofibers, is an area of growing concern for human health. Animal-based assays have been used to study the toxic effects of chemicals for many years. However, even so, very little is known about the potential toxicity of the vast majority of inhaled chemicals. As well as new or refined OECD test guidelines, continuing scientific developments are needed to improve the process of safety evaluation for the vast number of chemicals and inhaled materials. Although studying the toxic effects of inhaled chemicals is more challenging, promising in vitro exposure techniques have been recently developed that offer new possibilities to test biological activities of inhaled chemicals under biphasic conditions at the air liquid interface. This chapter gives an overview of inhalation toxicology as well as focusing on the potential application of in vitro methods for toxicity testing of airborne pollutants. PMID- 20358693 TI - Biological testing for drugs of abuse. AB - Testing for drugs of abuse has become commonplace and is used for a variety of indications. Commonly employed testing methods include immunoassay and chromatography. Testing methods vary in their sensitivity, specificity, time, and cost. While urine remains the most common body fluid used for testing of drugs of abuse, over the last several decades the use of alternative matrices such as blood, sweat, oral fluids, and hair has increased dramatically. Each biological matrix offers advantages and disadvantages for drug testing, and the most appropriate matrix frequently depends on the indications for the drug test. Drugs of abuse that are most commonly tested include alcohol, amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. Testing may involve detection of the parent compound or metabolites and sensitivity, specificity, and reliability of drug testing may vary depending on the drug being tested. Toxicologists have a responsibility to understand the strengths and limitations of testing techniques and matrices to be able to critically evaluate the results of a drug test. PMID- 20358694 TI - Drugs of abuse: management of intoxication and antidotes. AB - Illicit drug intoxications are an increasing public health problem for which, in most cases, no antidotes are clinically available. The diagnosis and treatment of these intoxications requires a trained clinician with experience in recognizing the specific signs and symptoms of intoxications to individual drugs as well as polydrug intoxications, which are more the rule than the exception. To make the diagnosis, the clinical observation and a urine toxicology test are often enough. Evaluating the blood levels of drugs is frequently not practical because the tests can be expensive and results may be delayed and unavailable to guide the establishment of a treatment plan. Other laboratory tests may be useful depending on the drug or drugs ingested and the presence of other medical complications. The treatment should be provided in a quiet, safe and reassuring environment. Vital signs should be closely monitored. Changes in blood pressure, respiratory frequency and temperature should be promptly treated, particularly respiratory depression (in cases of opiate intoxication) or hyperthermia (in cases of cocaine or amphetamine intoxication). Intravenous fluids should be administered as soon as possible. Other psychiatric and medical complication should receive appropriate symptomatic treatment. Research on immunotherapies, including vaccines, monoclonal and catalytic antibodies, seems to be a promising approach that may yield specific antidotes for drugs of abuse, helping to ameliorate the morbidity and mortality associated with illicit drug intoxications. PMID- 20358695 TI - Chemical warfare agents. AB - Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents. PMID- 20358696 TI - Biological warfare agents. AB - Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents. PMID- 20358697 TI - Forensic toxicology. AB - Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results. PMID- 20358698 TI - The Long-Term Career Outcome Study (LTCOS): where we've been and where we hope to go. PMID- 20358699 TI - Respecting our patients by respecting their records. PMID- 20358700 TI - Department of Defense position on patient movement during influenza A (H1N1) pandemic: implications for actions now. PMID- 20358701 TI - Clinical treatment of nondysentery travelers' diarrhea during deployment. PMID- 20358702 TI - Midterm health and personnel outcomes of recent combat amputees. AB - OBJECTIVE: Warfighters who sustained combat amputations in Operation Enduring Freedom or Operation Iraqi Freedom (OEF/OIF) have unique challenges during rehabilitation. This study followed their outcomes. METHODS: Subjects were 382 U.S. warfighters with major limb amputations after combat injury in OEF/OIF between 2001 and 2005. Outcome measures were diagnoses, treatment codes, and personnel events captured by health and personnel databases during 24 months postinjury. RESULTS: Most patients had multiple complications generally within 30 days postinjury (e.g., infections, anemia), with important exceptions (e.g., heterotopic ossification). Lower limb amputees had 50% more complications than upper limb amputees. Two-thirds of patients had a mental health disorder (e.g., adjustment, post-traumatic stress disorder), with rates of major disorder categories between 18% and 25%. Over 80% of patients used physical and occupational therapy, prosthetic/orthotic services, and psychiatric care. CONCLUSIONS: Combat amputees had a complex set of outcomes supporting the continued need for military amputee care programs. PMID- 20358703 TI - War-related illness symptoms among Operation Iraqi Freedom/ Operation Enduring Freedom returnees. AB - OBJECTIVE: Our objective was to determine the pattern of war-related illness (WRI) symptoms among returnees of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) living on Long Island, NY. METHODS: We conducted an anonymous mail survey of WRI symptoms of a random cohort of 786 returnees (718 male, 68 female) living on Long Island from among 5,500 who registered with the OIF/OEF Registry. RESULTS: From among the 786 returnees whom we surveyed, we subsequently excluded 111 whose surveys were either returned unopened or who changed address. Two hundred seventy-four of the remaining 675 returnees responded to the survey (a 41% response rate). Disabling WRI symptoms were documented in approximately 2/3 of the responders and 75% of these responders had two or more symptoms. CONCLUSION: War-related illness symptoms are very common among OIF/OEF returnees suggesting the need for management strategies targeting their symptoms. BACKGROUND: Military conflicts have produced war-related illness (WRI) among our troops and veterans since the Civil War. Common to all these WRIs are a group of symptoms including body pain, fatigue, headache, sleep disturbance, diarrhea, forgetfulness, and impaired concentration. Also common to them is the absence of a discernable pathophysiology. Because WRI is poorly understood, we cannot prevent new occurrences with each new engagement of our armed forces. PMID- 20358706 TI - Use of vacuum-assisted closure negative pressure wound therapy in combat-related injuries--literature review. AB - Despite surgical and technological advances, managing combat-related injuries remains challenging both within and outside of the war theater. Unique characteristics of a war theater such as environmental contamination, varying evacuation procedures, and differing levels of medical care, add to the complexity. The advent of body armor has increased blast survival rates and soldiers are surviving with increasingly mangled limbs that require lengthy, multifaceted care. An inherent high risk of infection contraindicates immediate closure for these wounds. There is growing reported use of negative pressure wound therapy with reticulated open-cell foam (NPWT/ROCF) as delivered by vacuum assisted closure (VAC) therapy (KCI Licensing Inc., San Antonio, TX) as an adjunctive therapy in these open soft-tissue combat wounds. This review evaluates the efficacy of NPWT/ROCF for adjunctive treatment of wartime wounds. Following a literature review, data are summarized and presented. PMID- 20358704 TI - Biochemical markers of possible immunodepression in military training in harsh environments. AB - Prolonged, exhaustive exercise frequently leads to an increased incidence of upper respiratory tract illness (URTI) which is linked to transient immunodepression. We investigated potential biochemical markers of stress and fatigue, and URTI symptoms as a surrogate of immunodepression, in US Marines undergoing intensive winter training at altitude. Selected plasma amino acids and leptin (p[Lep]) were measured as possible markers of fatigue and immunodepression, together with nonesterified fatty acids (p[NEFA]) and total antioxidant capacity (p[TAC]). Changes were observed in plasma free tryptophan (p[FT]), p[Gln], p[Lep], p[NEFA], p[TAC] but not branched chain amino acids (p[BCAA]). p[FT] decreased markedly. Resting p[Gln] decreased overall after one month at altitude. p[Gln] routinely decreases 1-2 hrs after prolonged exercise. Importantly, we observed early morning decreases in p[Gln], suggesting a cumulative effect of prolonged activity, stress, and fatigue. Concomitantly, individuals with highest illness scores had the greatest p[Gln] decrease: low p[Gln] may therefore be associated with a diminished stress tolerance. PMID- 20358705 TI - Pyruvate-fortified fluid resuscitation improves hemodynamic stability while suppressing systemic inflammation and myocardial oxidative stress after hemorrhagic shock. AB - OBJECTIVES: To determine whether controlled resuscitation with pyruvate-fortified Ringer's (PR) solution vs. conventional lactate Ringer's (LR) more effectively stabilizes mean arterial pressure (MAP) and suppresses myocardial inflammation postresuscitation. METHODS: Goats were hemorrhaged (255 +/- 22 ml) to lower MAP to 48 +/- 1 mmHg. Next, the right femoral vessels were occluded for 90 min to model tourniquet application. Beginning at 30 min occlusion, LR or PR was infused i.v. at 10 ml/min for 90 min. The femoral occlusions were released at 60 min infusion. RESULTS: At 4 h postocclusion, MAP (mmHg) was increased in PR (59 +/- 4) vs. LR (47 +/- 3) resuscitated goats (p < 0.05). PR also more effectively augmented circulating HCO3 and total base excess. Nitrosative stress, detected in myocardium 4 h after LR resuscitation, was suppressed by PR. Finally, PR prevented the increase in circulating neutrophils that accompanied LR resuscitation. CONCLUSIONS: Relative to LR, resuscitation with PR more effectively stabilized MAP, suppressed myocardial nitrosative stress and minimized systemic inflammation after hemorrhagic shock with hindlimb ischemia reperfusion. PMID- 20358707 TI - Splenic injury sustained during body hardening drills and the utility of ultrasound in a prehospital combat medical environment. AB - This report describes a case of intra-abdominal hemorrhage from body hardening drills in a U.S. soldier during Operation Iraqi Freedom. In body hardening, participants allow themselves to be repeatedly punched and kicked in an effort to impart physical resilience. Portable sonography was used to diagnose hemoperitoneum and to guide the decision for urgent surgical evacuation, ultimately resulting in splenectomy. The case illustrates the risks of body hardening, the medical challenges unique to a prehospital combat environment, and the utility of ultrasound in this setting. PMID- 20358708 TI - Evaluation of time required for water-only decontamination of an oil-based agent. AB - STUDY OBJECTIVE: The objective was to evaluate the time to decontaminate an area of skin exposed to an oil-based agent using a water-only decontamination protocol. METHODS: A fluorescent mock chemical/biological agent was created. Each of 20 subjects had his/her forearm sprayed with the agent. Each subject placed his/her arm under a decontamination shower, which provided water at a pressure of 60-70 psi and 35 degrees C. After 30 sec a black light was used by three evaluators to determine whether the agent was removed. The process of 30 sec decontamination and re-evaluation was repeated for a total of 5 min. The primary endpoint was proportion decontaminated over time. RESULTS: After 90 sec, 100% of subjects were decontaminated. CONCLUSION: Whereas the data suggest the possibility of rapid water-only decontamination, the applicability of this data in current form is doubtful, but provides a model as a basis for future study. PMID- 20358709 TI - Association of weight at enlistment with enrollment in the Army Weight Control Program and subsequent attrition in the Assessment of Recruit Motivation and Strength Study. AB - The ongoing obesity epidemic has made recruiting qualified Army applicants increasingly difficult. A cohort of 10,213 Army enlisted subjects was enrolled in the Assessment of Recruit Motivation and Strength (ARMS) study from February 2005 through September 2006. Overweight recruits obtained a waiver for enlistment (n = 990) if they passed a screening physical fitness test. Recruits were evaluated for enrollment into the Army Weight Control Program (AWCP) and discharged during the 15 months following enlistment. Enrollment was higher among overweight recruits than recruits who met entrance standards (men: adjusted OR = 13.3 [95% CI: 10.3, 17.2]; women: adjusted OR = 3.6 [3.3, 3.9]). Although the discharge frequency was higher in the waiver group than in those who met standards (25.4% versus 19.9%, p < 0.001), there were only 10 (0.5% of total) discharges directly attributed to weight. Granting overweight waivers through the ARMS program increases enrollment to the AWCP but has little effect on weight-related attrition. PMID- 20358710 TI - Meals ready to eat: a brief history and clinical vignette with discussion on civilian applications. AB - Meals ready to eat (MRE) have undergone many revisions of their origins in the trench ration from World War I. The MRE was implemented in 1980. Its design allows extended storage and easy, safe meal preparation. MRE sodium content varies by meal and may range from 1.6 g/meal to 2.3 g/meal. The average MRE contains 1,200 kcal. When consumed as intended, MREs are adequate for maintaining a soldier's physical parameters without undesirable consequences. The average soldier has a healthy cardiovascular system, has the ability to excrete high sodium loads, and has high insensible losses. The American Heart Association recommends limiting sodium to 2.3 g/day for the general population. Additionally, those with heart failure should limit sodium to 2 g/day. Excess intake of calories and electrolytes may lead to adverse outcomes in certain populations. We describe a case of heart failure exacerbated by regular MRE consumption and the "perfect storm" of risk factors encountered with postdisaster distribution of MREs to a civilian population. PMID- 20358711 TI - Corrective lens use and refractive error among United States Air Force aircrew. AB - Corrective lens use by military aviators is an important consideration in the design of head-mounted equipment. The United States Air Force (USAF) has periodically monitored lens use by aviators; however, it has been over a decade since the last study. We provide an update on the prevalence of corrective lenses and refractive error among USAF aircrew based on eyeglass orders processed through the Spectacle Request Transmission System (SRTS). Currently, 41% of active duty USAF pilots and 54% of other aircrew require corrective lenses to perform flight duties. Refractive errors are characterized by low to moderate levels of myopia with a mean spherical equivalent power of -1.01 diopters (D) for pilots and -1.68 D for others. Contact lenses, and more recently refractive surgery, reduce the number of aircrew that must rely on spectacles when flying; however, spectacle compatibility remains an important consideration in the cockpit. PMID- 20358712 TI - NO-Xplode: a case of supplement-associated ischemic colitis. AB - The most common cause of ischemic colitis (IC) is a sudden and transient reduction in splanchnic perfusion. In the younger population, medications are an increasingly recognized cause of ischemic bowel disease. Over-the-counter supplements may also lead to the development of ischemic colitis through similar effects. We present a case of ischemic colitis in a 42-year-old active duty service member after using the performance-enhancing supplement, NO-Xplode. In this report, we review the pharmacology of this supplement and its proposed mechanism of injury. PMID- 20358713 TI - Shotgun injury to the arm: a staged protocol for upper limb salvage. AB - Low-energy shotgun fractures involving the arm are complex injuries. Previously published reports have emphasized various problems associated with these injuries. This case report describes a low-energy shotgun wound managed by a staged treatment protocol involving: (1) a spanning external fixator and immediate soft tissue management, followed by (2) osteosynthesis and autogenous bone grafting and (3) epineural suturing of injured radial nerve, with a successful outcome. Although adequate debridement of the fracture and soft tissue wound is the key to open fracture management, some difference of opinion exists with regard to the timing of bone reconstruction and grafting. In severe type III open fractures, or in wounds that are marginal, it may be best to delay cancellous bone grafting until soft tissue has stabilized following acute trauma when the risk of infection has been minimized. If early coverage of vital structures is not possible, local or remote flap coverage may be necessary. PMID- 20358714 TI - Radiology corner. Case 45. Noncardiogenic pulmonary edema as a result of urosepsis. PMID- 20358715 TI - Call for individual action. PMID- 20358716 TI - Nursing by the numbers. PMID- 20358717 TI - Nurses step up to take on expanded role during pandemic. PMID- 20358718 TI - Plain D5W or hypotonic saline solutions post-op could result in acute hyponatremia and death in healthy children. PMID- 20358719 TI - Bridging the gap between research and the front line. PMID- 20358720 TI - Alberta's own fastest RN on ice. PMID- 20358721 TI - How is your nurse-thinking? PMID- 20358722 TI - Lymphoma diagnosed at inguinal hernia repair. AB - Tumors presenting in the inguinal hernia sac are considered to be extremely rare, with the more common neoplasms metastasizing from the gastrointestinal tract, ovary and prostate. We report the case of Mantle cell lymphoma identified in the inguinal hernia sac following hernia repair While the hernia sac appeared normal to the surgeon, evaluation by the pathologist showed subtle gross irregularities, with subsequent histologic and immunochemical diagnosis of Mantle cell lymphoma. Twelve previous cases of a lymphoma diagnosed during hernia repair have been described in the English literature. This is the first report of Mantle cell lymphoma found in the hernia sac. This case illustrates the value of routine microscopic evaluation of hernia sacs found from inguinal/femoral herniorrhaphies, as it may be the primary presentation of an asymptomatic metastatic lymphoma. Additionally it underscores the importance of the surgeon's role in screening hernia sacs if the practice of submitting only macroscopically abnormal specimens for microscopic evaluation is adopted. PMID- 20358723 TI - A case report of urachal abscess: a rare differential in adult abdominal pain. AB - A 59-year-old woman presents with decreased appetite and abdominal pain. Her symptoms lead to lethargy and weakness. Abdominal pain is a common presentation in the primary care and emergency room setting. She was initially diagnosed with an abscess and treated with antibiotics and drainage. Upon further evaluation and cystoscopy she was discovered to have a urachal cyst. Urachal cysts are extremely rare and even more uncommon in adults, as it is usually diagnosed in children. It is an important diagnosis not to miss in the differential of adult abdominal pain as surgical intervention is often necessary for treatment. This case highlights urachal cyst as a rare and serious differential of adult abdominal pain. PMID- 20358724 TI - Diversifying residents' outpatient psychiatry experience: a contemporary model for academic outpatient psychiatry clinics. AB - A diversified, outpatient experience is an important part of psychiatric training, yet challenging to attain. We describe a multiple, subspecialty psychiatry clinic model for 3rd year psychiatry residents. Evaluation findings based on its initial implementation indicated improved resident supervision, better therapeutic alliance and an overall increase in satisfaction. This model facilitates resident exposure to diverse patients and treatment modalities as well as faculty development of expertise. It also promotes academic training excellence. PMID- 20358726 TI - Disparities in health, obesity and access to care among an insured population of Asian and Pacific Islander Americans in Hawai'i. AB - OBJECTIVE: To examine differences in health status, obesity and access among Asian and Pacific Islander Americans in Hawai'i using data from a 2007 health plan survey, including Caucasians, Puerto Ricans, American Indian and Alaska Natives, Chinese, Filipinos, Japanese, Koreans, Native Hawai'ians, Samoans, and Other Pacific Islanders. METHODS: Data were collected through a stratified random sample of adult members of a health plan in Hawai'i (n = 119,563) who saw a physician in the past 12 months. Multivariable logistic and ordinary least squares regression analyses were used to examine racial/ethnic differences in health status, access, and obesity and the impact of obesity and access on health status, after controlling for age, gender, and education. RESULTS: The highest obesity rates were found among Samoans (50%), Puerto Ricans (37%), Native Hawai'ians (36%), and Other Pacific Islanders (35%). Puerto Ricans and Samoans reported the highestnumber of poor physical health days (5.4). Samoans reported the highest number of poor mental health days (4.4). Obesity had a stronger impact than access on self-reported health status. CONCLUSION: Samoans had the highest rate of obesity, low health ratings, and a high number of days of poor health. Targeted interventions may be needed for this group. PMID- 20358725 TI - Intussusception and colonic ischemia in portal hypertension: a case report. AB - Intestinal intussusception is a relatively uncommon occurrence in adults in comparison to pediatric patients. While the management of intussusception in children is frequently decompression of the involved segment, adults often require surgical resection secondary to frequent association with neoplastic lead points. A less common reason for surgical removal of an intussuscepted segment in adults is the development of ischemic colitis. The authors present an unusual case of adult intussusception with associated ischemic colitis in a patient with portal hypertension awaiting liver transplantation. Portal hypertension is associated with the development of a microvascular colopathy This condition may serve as the lead point for intestinal intussusception. Furthermore, the vascular changes of portal hypertension leave the bowel unable to respond appropriately to the threat of ischemia. The colopathy of portal hypertension may have predisposed our patient to the development of colonic intussusception by submucosal vascular engorgement; it may have also rendered the intussuscepted segment more susceptible to the development of ischemia. PMID- 20358727 TI - Use of an atriocaval shunt in a trauma patient: first reported case in Hawai'i. AB - BACKGROUND: Traumatic injuries to the retrohepatic vena cava are typically fatal. Emergent access to this area is difficult and patients typically exsanguinate before the injury can be identified and fixed. OBJECTIVE: To report the use of an atriocaval shunt in the repair of an injury to the retrohepatic vena cava from a gunshot wound. CASE REPORT: A 24-year-old man was shot in his right chest suffering a penetrating injury to the liver and inferior vena cava. Surgical repair was performed with the aid of an atriocaval shunt fashioned from a chest tube. He survived and recovered without incident. CONCLUSION: Atriocaval shunting maybe a life-saving option for uncontrolled hemorrhage from injuries to the retrohepatic vena cava. PMID- 20358728 TI - Developing shortage of physicians. PMID- 20358729 TI - 2010 election campaign. PMID- 20358731 TI - Achieving quality in life and death. PMID- 20358730 TI - Inspired midwife. PMID- 20358732 TI - Collaboration amendment insulting to nurses and midwives. PMID- 20358733 TI - New nurses award 2010: your questions answered. PMID- 20358734 TI - Industrial fair work resolution. PMID- 20358735 TI - Avoiding litigation--a matter of consent. PMID- 20358736 TI - Pre-hospital clinical management of heat stress. PMID- 20358737 TI - Passion for midwifery. PMID- 20358738 TI - Promoting careers in health to indigenous youth. PMID- 20358739 TI - Revolution in indigenous maternal health gathers momentum. PMID- 20358740 TI - PEPA: bridging the gap in palliative care. PMID- 20358741 TI - Making sexual health services accessible. PMID- 20358742 TI - Empowering indigenous families. PMID- 20358743 TI - Show some emotion. PMID- 20358744 TI - Is your practice becoming a 'home'? PMID- 20358745 TI - CMS defines 'meaningful use'. Proposed rule outlines requirements for EHR incentive payments. PMID- 20358746 TI - Charity begins at home, not in the office. The evolving nature of charity care in medical groups. PMID- 20358747 TI - 5 ways to enhance patient check-in. PMID- 20358748 TI - Back to better-performing practice basics. PMID- 20358749 TI - Walk the line. Balance the needs of all stakeholders when developing care systems. PMID- 20358750 TI - Patients treated together can improve together. Are shared patient visits right for your practice? AB - Consider offering group visits to increase physician productivity, enhance satisfaction among doctors and patients, and boost patients' knowledge of their health conditions. PMID- 20358751 TI - United we stand. The formula for creating a "megagroup". PMID- 20358752 TI - [Dyspnea in a high performance athlete. Differential "asthma" diagnosis]. PMID- 20358753 TI - [Patient criticizes treatment? Remaining calm and admitting no guilt!]. PMID- 20358754 TI - [Nutrition counseling: what can I offer my patients?]. PMID- 20358755 TI - [Disregarded guidelines--inadequate training--poor intensive care management]. PMID- 20358756 TI - [What is mainly inadequate in resuscitation. Clueless in an emergency (interview by Dr. med. Jochen Aumiller)]. PMID- 20358757 TI - [Depression and depressive symptoms]. PMID- 20358758 TI - [Optimal therapy of cardiologic illnesses--age is not an exclusion criterion]. PMID- 20358759 TI - [Allergy and environment. A chronic, irritating matter]. PMID- 20358760 TI - [What the general practitioner should know about food allergy]. PMID- 20358761 TI - [Interaction between viral respiratory infections, allergy and air pollution in asthma patients]. PMID- 20358762 TI - [Polyposis nasi--conservative measures versus surgical treatment]. PMID- 20358763 TI - [Estrogens--wound dressings--vacuum therapy. How chronic wounds can still heal]. PMID- 20358764 TI - [Diverticulitis: what's new?]. PMID- 20358765 TI - [Aspirin-induced asthma in patients with osteoarthritis]. PMID- 20358766 TI - [Positive added effect of telmisartan. New therapy alternative for a large collection of cardiovascular risk patients]. PMID- 20358767 TI - [Histogenetic and neurodegenerative processes in the nervous system using heterotopic neurotransplantation]. AB - The aim of this article was to summarize the author's own experimental data and the data available from literature on the neurotransplantation in the ectopic sites such as peripheral nerve (mainly) and rat anterior eye chamber. The review examines issues relating to the following problems: histogenesis and survival of neural tissues after transplantation, host/transplant tissue interactions, the fate of long-term transplants, co-transplants of different embryonic anlages, dorsal root ganglion grafting, the effects of various trophic factors on graft development. The review discusses the new data on stem cell transplantation into a peripheral nerve. PMID- 20358768 TI - [Novel calretinin-positive cells with polymorphous spines in the mouse forebrain during early postnatal ontogenesis]. AB - Using an immunocytochemical method for calretinin (CR) detection, we have earlier described (Morfologiya, 2009 v. 135. No. 3, p. 7-19) the population of previously unknown mono- and bipolar cells with polymorphous spines (PS) covering their cell bodies and processes, in adult mice forebrain structures adjacent to anterior horn of lateral ventricle. CR-positive spiny (CR+PS) cells were negative to GAD67 and were detected in the white matter and in layers V and VI of frontal area of dorsomedial cortex close to the cingulum, in in rostro-dorsal part of the caudate nucleus-putamen complex, anterior olfactory nucleus and in subependymal layer of the dorso-lateral angle of the lateral ventricle. In this work, the distribution of these cells in 7-day-old mice was studied. Comparative topographical analysis of definitive and early CR+PS cells demonstrated that in 7-day-old mice CR+PS cells were absent from the areas of their localization in adult animals - anterior olfactory nucleus, cortical plate and inner portion of neostriatum. Meanwhile, some CR+PS-like cells were detected in 7-day-old mice inside the rostral migratory route, close to neostriatum anterior boundary, along the dorsal border between neostriatum and corpus callosum, subependymal layer of lateral wall of the lateral ventricle, and in the cingulum area. These findings are indicative of the possible postnatal appearance of CR+PS cells. To test this hypothesis, the experiments were conducted in which bromodeoxyuridine (BrdU) was administered to the mice on their postnatal days 2-4 with the subsequent study of the brain sections of these animals sacrificed on their postnatal day 20. Double immunolabeling of these sections for CR and BrdU has detected the presence of CR+PS cells that contained postnatally administered BrdU. These results strongly suggest that, at least, some portion of CR+PS cells have their mitosis postnatally. It may be assumed, that CR+PS cells migrate to the sites of their distribution in adult animals from day 7 till day 20 of postnatal develpment. PMID- 20358769 TI - [Neuronal division or enucleation]. AB - In this work,using the classical neurohistological Bielschowsky-Gros method, all the morphological phenomena were reproduced that were earlier interpreted by many authors as the signs of neuron division, budding and fission. It is suggested that these phenomena are associated with the effect of enucleation demonstrated in many cells of other tissue types exposed to different physical and chemical factors. The experiments were conducted in tissue culture, using the isolated neurons of the mollusk Lymnnaea stagnalis, in which the neural cells were treated with actin microfilament inhibitor cytochalasin B. Phase-contrast time-lapse video recording during 4-8 hours demonstrated the effects of nucleus displacement, ectopy and bulging up to almost complete fission of neuronal body. These effects reproduce the images obtained in static fixed preparations under "normal" and various experimental conditions. Sometimes, at the early experimental stages, the bulging of cytoplasm was also detected. Control experiments in which the neurons were treated with the culture medium containing cytochalasin B solvent dimethyl sulfoxide, showed no changes in neurons during 8 hour period. It is suggested that the images, interpreted earlier as neuron division or fission, could be explained by inhibition of actin microfilaments, which sometimes may develop spontaneously in cells experiencing individual metabolic changes compromising the cytoskeleton stability maintenance. PMID- 20358770 TI - [Changes in neurons and gliocytes of the rat mesoaccumbocingulate system following perinatal morphine administration]. AB - To study the changes of neuron and gliocyte numbers and some morphometric parameters in mesoaccumbocingulate (MAC) dopaminergic system of rats after pre- and postnatal opiate treatment, 0.1 mg dose of 1% morphine hydrochloride solution was injected into the fetal amnion of Wistar female rats (n=4) at Day 17 post fertilization and intraperitoneally into newborn rats (n=4) at postnatal Day 4. Perinatal influence of morphine on MAC-system in rats resulted in the chromophilic degeneration, swelling and death of some part of neurons, decrease in the volume of the other (slightly injured) neurons. Neuronal injury was more pronounced after prenatal morphine treatment and was accompanied by the increase in both microgliocyte cell number and phagocytic activity. Morphine administration induced no changes in the satellite macrogliocyte number and in the average distance between these cells and the bodies of slightly injured neurons. PMID- 20358771 TI - [Effect of mild hypobaric hypoxia in the preconditioning regime on expression of pCREB and NF-kappaB transcription factors in the rat hippocampus before and after severe hypoxia]. AB - Preconditioning using threefold mild hypobaric hypoxia (HH) is known to increase the tolerance of vulnerable brain neurons to severe hypoxia and other damaging factors. In the present study, the changes of the expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB (cAMP response element binding protein) were studied in the hippocampus of rats preconditioned by mild hypoxia. Using immunocytochemical method, it was demonstrated that HH increased NF-kappaB and phosphorylated CREB (pCREB) immunoreactivity in CA1-CA4 fields of the hippocampus and gyrus dentatus. It also contributed to the up-regulation of the expression of these transcription factors in the hippocampus of preconditioned rats 3-24 h following severe HH. These findings suggest that NF kappaB and CREB are involved in HH-activated mechanisms of brain tolerance development. PMID- 20358773 TI - [Morpho-functional changes in the frog urinary bladder receptors under the influence of barbiturates]. AB - The effect of hexenal and nembutal on the tissue bushy receptors was studied the living isolated frog urinary bladder using methylene blue staining. These drugs were shown to induce the changes in the receptor pulse activity which included three phases: an initial sharp increase, an abrupt decline and a low protracted plateau. Reactions to hexenal and nembutal, while possessing some common features, had their own peculiarities. Synchronously, the dynamics of methylene blue staining of the receptor elements was registered for the control of the intensity of oxidation-reduction processes in the receptor neuroplasm, that is for redox-system dynamics. It was found that the phases of this dynamics coincided in many respects with the phases of the receptor electric activity changes. No ultrastructural changes associated with the putative damaging effect of barbiturates on the receptors were recorded (during the exposure of 1-30 min). The most significant characteristic was an accumulation glycogen granules in the neuroplasm of the receptor elements, suggesting the prevalence of energy substrate deposition over its expenditure. Depression of the receptor pulse activity supports the assumption that barbiturates, besides their soporific and narcotic actions, apparently possess some anesthetic property. PMID- 20358772 TI - [Morpho-functional changes in the goldfish Mauthner neurons after beta-amyloid application]. AB - The influence of aggregated beta-amyloid peptide fragment 25-35 application on three-dimensional structure and volume of Mauthner cells (MCs), as determined by reconstruction from serial histological sections, and on goldfish motor asymmetry was studied. It was shown that in intact and control goldfish motor asymmetry was stable and strongly correlated with structural asymmetry of neurons. But under the influence of beta-amyloid, motor asymmetry appeared to be strongly changed or inverted, did not correlate with structural asymmetry and frequently even was opposite to it. This resulted from strong dystrophy or, on the contrary, hypertrophy of individual neurons and their separate dendrites with the change in the proportions between them. It is suggested that injurious effect of beta amyloid peptide on MCs structure, discordant with ("irregular") fish behavior, could be the result of mechanical deformation, induced by ribbon-like fibrils of amyloid peptide. These findings collectively suggest that MCs are the adequate object for the study of the structural aspects of amyloidosis. PMID- 20358774 TI - [Histochemical study of the myocardium structure in the heart contusion]. AB - The experimental modeling of heart contusion which was accompanied by ventricular fibrillation development was performed in Wistar rats, with the electrocardiographic study and subsequent histological and histochemical examination of the myocardium samples. Following heart contusion, acute circulatory disturbances, muscle fiber fragmentation, cardiomyocyte overcontraction or relaxation were detected in the myocardium. Also, the increase of total and intracellular calcium ion content in the myocardium was demonstrated. It is suggested that the mechanism of ventricular fibrillation development after heart contusion is associated with the increase of calcium concentration in both the cardiomyocytes and intercellular spaces leading to uncoordinated cardiac contractions. PMID- 20358775 TI - [Evaluation of the endothelial monolayer after re-endothelization of the thoracic duct cryodestruction area]. AB - Using the standard cryodestruction model, the peculiarities of reparative regeneration were studied in cat thoracic duct endothelium. Material was collected 12 hours, 1, 2 and 3 days after the injury and was analyzed using scanning electron microscopy. The restoration of the endothelial layer was shown to be completed by day 3 due to cell migration and proliferation at the margin of cryodestruction zone. The degree of tissue regeneration was evaluated using the topological and informational parameters. The results demonstrated the imperfect completion of regeneration process by day 3; the borderline state of the cellular system was detected together with the possibility of the disturbance of endothelial lining reorganization process. Thus, the informational parameters may be used as the complementary criteria for the assessment of the processes, cellular system state and functioning. PMID- 20358776 TI - [Structural changes in the rat intestinal wall during starvation]. AB - The aim of this study was to determine the effect of starvation on all the tunics of duodenum and rectum wall. The animals were 20 outbred albino rats; the control group comprised 4 animals. The animals were starved while the drinking regime remained unchanged. Material was obtained at days 3 and 6 of starvation and was studied using electron microscopy. The changes were detected in the structure of mucosa, submucosa, tunica muscularis and serosa. These structural changes were of similar nature in all the tunics and differed only by the degree of their severity. The most pronounced changes were observed in all the epithelial cell types (absorbing, goblet and endocrine) in both parts of the intestine. These included cell flattening, microvilli reduction and deformation, mucus production disturbances, destructive changes in the mitochondria (swelling, cristae reduction, vacuoles and myelin-like structures formation, disruption of both mitochondrial membranes). PMID- 20358777 TI - [Response mechanisms of the airway smooth muscle tissue in experimental bronchial spasm]. AB - This investigation was aimed at the complex evaluation of the reactivity mechanisms of bronchial smooth muscle tissue (SMT) in experimental bronchial spasm. Morphometric, cytospectrophotometric and electron microscopical analysis demonstrated the presence of three types of smooth muscle cells (SMC) within the bronchial SMT (small, medium, large), that differed in their linear and metabolic parameters. The findings of this study indicate that under the conditions of experimental bronchial spasm development, the ratios of SMC in bronchial SMT are changed with the increase in proportion of small SMC and the elimination of large SMC. In the dynamics of experimental bronchial spasm development, the activation of cytoplasmic synthesis as well as of DNA synthesis was detected mainly in group of small SMC. The reactive-dystrophic changes were marked at the subcellular level, that were most often identified in large SMC resulting in their elimination from population in the dynamics of an experiment. The data obtained suggest that one of the important mechanisms of airway SMT adaptation to the bronchial spasm development is a dynamic reorganization of SMC population. PMID- 20358778 TI - [Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease]. AB - The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD. PMID- 20358779 TI - [Structural and functional changes of the foot after cyclic centrifugal physical loads in sports runners]. AB - Foot structural and functional peculiarities after cyclic centrifugal physical loads in sports runners were studied. The work demonstrates the results of computer morphometry of 120 athlete runners (50 boys and 70 girls) aged 15-17 years--the students of Volgograd School of Olympic Reserve and Volgograd State Academy of Physical Education. Cyclic centrifugal loads of shock-type (long run on an inclined plane) resulted in significant reduction of the foot arch hight. In female runners, the reduction was found mainly in the longitudinal foot arch, while in male runners it was detected in transverse foot arch. Two basic types of foot arch reaction to prolonged cyclic loads were detected. This allowed us, for the first time, to divide the static flat-footedness into two major categpries: compensated, or dynamic, and true. In compensated static flat-footedness, the structural and functional foot parameters returned to their initial levels after the rehabilitation, while in true flat-footedness the complex rehabilitation measures could not restore the initial morpho-functional parameters: foot arches remained reduced. PMID- 20358780 TI - [Computer assessment of membrane structure in various erythrocyte forms]. AB - The photometric computer image analysis method is described. It is based on the creation of the gallery of the images of various erythrocyte forms (discocytes, ecchinocytes, target cells and degenerative forms). Using the Bio Vision program, the structure of membranes of each type of erythrocytes was studied. It was found that the morpho-functional changes of erythrocytes of various degrees were accompanied by the alterations in the relative content of condensed membrane protein-lipid complexes. PMID- 20358781 TI - [Juxtaoral organ of Chievitz]. AB - This review presents the analysis of the systematized data on human juxtaoral organ (JOO) development, structure and function based on the results of classical and recent morphological studies. JOO morphogenesis is traced, including the appearance of its anlage at the bottom of the primitive mouth, epithelial invagination into the mesenchyme, JOO detachment from the oral epithelium, its innervation, connective tissue capsule formation, and final maturation. The analysis of the results of macroscopical, histological, electron microscopical, histochemical and immunohistochemical studies is presented, suggesting high metabolic and synthetic activity of its epithelium, which expresses several neural markers, and emphasizing a rich innervation of both its epithelial and stromal components. The findings supporting the concepts of JOO secretory and mechanosensory functions, are examined. The data on the differential diagnosis between JOO and tumoral processes are discussed, as well as the pathological changes of JOO itself and their significance for the diagnosis of the diseases. PMID- 20358782 TI - [Proliferation markers used in histological studies]. AB - The present paper reviews the current approaches used to study cell proliferative activity. In the last years, a number of proteins involved in cell cycle control were discovered, that may serve as selective markers of proliferating cells. This work gives the characteristics of immunocytochemical methods demonstrating 5 bromodeoxyuridine, PCNA, Ki-67, FEN-1, phosphorylated histone H3 and cyclins. The data on the role of these proteins in cell cycle control are presented. PMID- 20358783 TI - [Conducting myocytes of the heart (on the 170th anniversary of discovery)]. PMID- 20358784 TI - [All-Russian Congress of Anatomists, Histologists and Embryologists (Saratov, September, 23-25, 2009)]. PMID- 20358785 TI - Cranio-maxillofacial trauma: clinical presentation, aetiology and management. PMID- 20358786 TI - Presentation and management of maxillofacial trauma in Dar es Salaam, Tanzania. AB - OBJECTIVE: To describe the presentation and management of maxillofacial trauma. DESIGN: A retrospective study. SETTING: Department of Oral and Maxillofacial Surgery, Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. SUBJECTS: Patients presenting with maxillofacial trauma at the oral and maxillofacial surgery department of the MNH over a six year period (2001-2007). METHOD: Information was gathered including age, gender, length of interval between injury and presentation to the hospital, aetiology, pattern of soft tissue injury and fractures, therapy, co-morbidity, complications and number of hospitalisation days. RESULTS: The 21-30-year old age group was most affected. The overall male to female ratio was 4.3:1. The major cause of maxillofacial trauma was road traffic accidents (42.3%), followed by assaults (39.1%). Over 90% of the patients sustained soft tissue injuries, with cut wounds seen most frequently (45.0%). Of the soft tissue injuries, 75% required surgical intervention. Most of the fractures were located in the mandible (52.8%). Accompanying injuries elsewhere in the body occurred in 51.5%. Complications occurred in 13.3% of the cases. The mean hospitalisation period was 4.3 days. CONCLUSION: Road traffic accidents and assaults were the most common causes of maxillofacial trauma. Males below forty years of age were the majority of the victims. PMID- 20358787 TI - Post-prandial glucose levels and consumption of omega 3 fatty acids and saturated fats among two rural populations in Kenya. AB - BACKGROUND: Amount and quality of dietary fat modifies glucose tolerance. Omega 3 Fatty Acids (n-3F A) are polyunsaturated fats, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found primarily in fish and they have a positive effect on glucose tolerance. OBJECTIVE: To compare risk of type 2 diabetes mellitus (T2DM), as demonstrated thourough impaired glucose tolerance (IGT), and n-3FA intake among two rural populations. DESIGN: A descriptive, cross-sectional comparative study. SETTING: Bondo District (Luo Community) and Kericho District (Kipsigis Community) of the Lake Victoria basin of Kenya. SUBJECTS: Sample of 150 individuals, aged above 18 years was randomly selected from each of the two communities. INTERVENTIONS: Impaired glucose tolerance (IGT) was measured according to World Health Organisation diagnostic criteria. The intake of n-3FA was determined using a 24 hour dietary recall and food frequency schedule. Data was analysed using SPSS and Pearson Correlation Coefficient was used to test correlation between n-3FA consumption and IGT. The inter-group comparisons were done using the t-test and analysis of variance. RESULTS: The prevalence of IGT was 11.8% among the Kipsigis and 4.8% among the Luo (P<0.001). The mean EPA and DHA intake was found to be 0.29 g/day and 0.34 g/day respectively among the Luo and 0.01 g/day and 0.01 g/day among the Kipsigis (P<0.001). The relationship between 2 hour post-prandial glucose level and consumption of DHA was (r=-0.111, p<0.05), EPA (r=-0.123, p<0.05), polyunsaturated fatty acids (r=-0.128, p<0.05) and saturated fats (r=-0.002, p=0.973). CONCLUSION: The levels of IGT were significantly lower (P<0.001) among the Luo, than among the Kipsigis. There was also evidence of significant inverse relationship between IGT and consumption of n-3FA and polyunsaturated fatty acids (PUFA) but no association between saturated fats intake and IGT. The saturated fat ingested did not affect the level of post prandial glucose. The Luo who consumed higher n-3FA amounts, recorded lower levels of IGT than the Kipsigis who had significantly lower consumption. RECOMMENDATIONS: Effective screening methods should be used at the existing health units to determine risk factors of type 2 diabetes mellitus like IGT among patients. This could help in advising them accordingly on lifestyle changes, especially concerning diet and beneficial fats. PMID- 20358788 TI - Pregnancy outcome in booked and unbooked mothers in South Eastern Nigeria. AB - BACKGROUND: In order for individual health institutions in Nigeria to contribute towards the achievement of the Millennium Development Goals (MDG) with regards to maternal health, there is need for research on the local causes of and factors influencing adverse maternal outcomes. This would enable care providers and policy makers appreciate the burden of the problem and know where to focus as they distribute resources. OBJECTIVES: To compare the socio-demographical characteristics, obstetrical complications and foetal outcome in booked verses unbooked mothers who delivered at this hospital. DESIGN: A hospital based retrospective study. SETTING: The Abia State University Teaching Hospital (ABSUTH), Aba in South Eastern Nigeria. SUBJECTS: Three thousand, seven hundred and thirty four mothers who delivered in the hospital between 1st January 2005 and 31st December 2007. RESULTS: Unbooked mothers constituted 17.0% of the 3734 deliveries in the studied period. Compared to booked mothers, unbooked mothers were younger in age (28.2 +/- 5.80 vs. 29.3 +/- 6.04; p<0.001) and had a lower educational status (P<0.001). Majority of the unbooked were of lower social class; p<0.001. Unbooked mothers had a statistically significant higher incidence of pre-eclampsia/eclampsia (OR 3.88; 95%CI 2.61-5.77; p<0.001) and were 13 times more likely to die in the hospital than booked patients (OR: 13.54; 95%CI: 6.89 27.03); p<0.0001). Unbooked mothers were about half as likely to deliver by spontaneous vaginal delivery compared to booked mothers (OR 0.64; 95%CI 0.55 0.73; P<0.001) and eight times more likely to be delivered by emergency laparotomy due to uterine rupture than booked mothers (OR 8.80; 95%CI 3.84-20.55; P<0.001). Unbooked mothers were nine times more likely to have babies with birth asphyxia. CONCLUSION: The study showed a positive correlation between lack of proper antenatal care and adverse pregnancy outcome with poorer outcomes in unbooked than booked patients. Improving the availability and accessibility of quality antenatal and delivery care services in our environment will improve pregnancy outcome. PMID- 20358790 TI - Molecular typing and antibiotic susceptibility patterns of enteropathogenic and shigatoxin producing Escherichia coli isolated from food handlers in three areas of Kenya. AB - OBJECTIVES: To determine the aetiology, epidemiology and sanitary factors of carriage of enteropathogenic Escherichia coli (EPEC) and Shiga-toxin producing E. coli (STEC) in food-handlers working in tourist hotels in three popular tourist destinations in Kenya. DESIGN: Cross sectional laboratory based study. SETTING: Three tourist destinations of Nairobi, Malindi and Diani in Kenya. SUBJECTS: Food handlers who were working in hotels frequented by tourists in the three study sites. RESULTS: Overall, during the period of April 2003 to May 2004, a total of 1399 food handlers stool samples were collected and analysed. EPEC expressing the eaeA gene and STEC expressing the stx2 gene were detected in 11/1399 (0.8%) and 2/1399 (0.1%) of the study subjects respectively. The mean age of the subjects from whom EPEC and STEC were isolated was similar (32.6 years) to those from whom no EPEC and STEC were isolated (32.5 years). Prior use of antibiotics, water source and toilet types were not significantly associated with the isolation of EPEC and STEC (p>0.05). There were 11 resistance patterns with six isolates (6/13, 46.2%) showing multidrug resistance. High prevalence of resistance was observed to co-trimoxazole (55.6%), chloramphenicol (33.3%), ampicillin (22.2%) and tetracycline (22.2%). High concentrations of antibiotics were required to achieve MIC90 for tetracycline, (>64 mg ml(-1)) and ampicillin (>256 mg ml(-1)). Cluster analysis of the Pulse Field Gel Electrophoresis profiles revealed that the EPEC and STEC isolates belonged to two main genotypes with 11 distinct DNA fragment profiles. CONCLUSION: This is the first report in Africa on the isolation of STEC from food handlers working in tourist hotels. These food handlers who carry the STEC and EPEC could potentially infect tourists and other people through food or water contamination in the hotel settings and thus our findings are of great public health importance. PMID- 20358789 TI - Intestinal polyparasitism in a rural Kenyan community. AB - BACKGROUND: Polyparasitism seems to be a common feature in human populations in sub-Saharan Africa. However, very little is known about its epidemiological significance, its long term impact on human health or the types of interactions that occur between the different parasite species involved. OBJECTIVES: To determine the prevalence and co-occurrence of intestinal parasites in a rural community in the Kibwezi, Makueni district, Kenya. DESIGN: A cross sectional study. SETTING: Kiteng'ei village, Kibwezi, Makueni district, between May and September 2006. SUBJECTS: One thousand and forty five who comprised of 263 adult males, 271 adult females > 15 years of age and 232 boys, and 279 girls <15 years of age. INTERVENTIONS: All infected members of the community were offered Praziquantel (at dosages of 40 mg/kg body weight) for Schistosomiasis and Albendazole (600 mg) for soil transmitted helminths. RESULTS: A total of ten intestinal parasite species (five protozoan and five helminth parasite species) were present in this community and polyparasitsm was common in individuals 5-24 years of age with no gendar related differences. Most of the infections were mild. The protozoan parasites of public health significance present were Entamoeba histolytica and Giardia lamblia with prevalence of 12.6% and 4.2%, respectively. The helminth parasites of public health significance in the locality were Schistosoma mansoni with a prevalence of 28%, and hookworms prevalence of 10%. About 53% of the study population harboured intestinal parasite infections, with 31% of the infected population carrying single parasite species infections, and 22% harbouring two or more intestinal parasite species per individual. Significant positive associations (p values <0.05) were observed between S. mansoni and hookworms, hookworms and Hymenolepis. nana and Entamoeba histolytica and Entamoeba coli. CONCLUSION: Intestinal polyparasitism was common in the Kiteng'ei community, particularly in individuals aged of 5-24 years old. An integrated control programme of approach would be recommended for the control of S. mansoni, hookworms and Entamoeba histolytica for this community. PMID- 20358791 TI - General and regional anaesthesia for thyroidectomy in rural/semi-urban Nigerian centres. AB - OBJECTIVE: To evaluate the feasibility and benefits of regional anaesthesia (RA) for thyroidectomy in rural/semi-urban centres. DESIGN: A prospective study. SETTINGS: Missionary Hospital Saki, Nigeria and Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. SUBJECTS: One hundred and seventy five patients with goitre. RESULTS: The average time for the anaesthetists to put patients to sleep was 4.06 +/- 1.02 minutes, while it took 17.8 +/- 2.9 minutes to give the regional block. Post operative laryngeal complications in RA group were very minimal, while in general anaesthesia (GA) group, there were significant complications in 32 (36%) patients laryngeal oedema 15 (17%), erosions in 10 (11%) and ulcer in seven (8%). Cost of surgery in GA was thrice as much as in RA group. Thirty one (35%) with GA had steam inhalation for sore throat. It was possible to converse (laryngeal nerve monitoring) with the patient during operation but not possible with GA group. There was early discharge of patients in RA group. CONCLUSION: Regional/local anaesthesia is feasible for some cases of thyroidectomy with a lot of advantages and specifically allows surgeons to converse with the patients during operation-direct laryngeal and other nerve monitoring. Despite advancement in cuff design a lot of lesions still occur from endotracheal intubations. PMID- 20358792 TI - Therapeutic misconception and clinical trials in sub-Saharan Africa: a review. AB - OBJECTIVES: To identify possible existence of therapeutic misconception and its effects on clinical trials in sub-Saharan Africa. DATA SOURCE: Original research findings and reviews published in the English literature and author's professional experience with clinical trials in some East, Central and West African countries. DESIGN: Review of peer-reviewed articles. DATA EXTRACTION: Online searches and requests for reprints from corresponding authors and institutional subscription. DATA SYNTHESIS: Information categorised accordingly. RESULTS: Therapeutic misconception, defined as a conflation by research subjects of research goals and those of routine health care is considered widely prevalent globally. The subjects misunderstand the disclosures during consenting process and enroll hoping to derive personal benefits from the study. Though no study has looked at therapeutic misconception specifically in sub-Saharan Africa, available evidence suggests that it is prevalent. Therapeutic misconception is incompatible with informed voluntary consent. It may affect participation in clinical trials, subjects' safety and well-being and possibly the research findings. CONCLUSIONS: There is need for studies to identify the prevalence and effects of therapeutic misconception in the region. Researchers in sub-Saharan Africa should be aware of its existence, thus design trials in which it will not have significant effects and strengthen the consent process to reduce it. PMID- 20358793 TI - Vertex epidural haematoma manifesting with bilateral upper limb decerebrate posture: case report. AB - Vertex epidural haematomas (VEDH) are rare and difficulties are encountered in diagnosis and management. This is a case report of a patient with a vertex epidural haematoma who presented with signs of severe head injury with upper limb decerebrate posture. We discuss the challenges of radiological investigation and neurosurgical management of VEDH. PMID- 20358794 TI - [Quality of life--at last]. PMID- 20358795 TI - [The person, not the wound should be in the center]. PMID- 20358796 TI - [The palliative nurse as rescuer of the culture]. PMID- 20358797 TI - [Versatility can be learned]. PMID- 20358798 TI - [Matters about a person does not know show a person who does not know himself]. PMID- 20358799 TI - [What are the quality indicators for team work?]. PMID- 20358800 TI - [Effective nursing prevention of delirium]. PMID- 20358801 TI - [First nurse president]. PMID- 20358802 TI - ["I have been your woman for sixty years..."]. PMID- 20358803 TI - [Reflections on everyday ordinariness]. PMID- 20358804 TI - [Support for mourning parents]. PMID- 20358805 TI - [In search of a consensus and established criteria]. PMID- 20358806 TI - ["The question is not the solution"]. PMID- 20358807 TI - [Determination of trace metals in atmospheric dry deposition with a heavy matrix of PUF by inductively coupled plasma mass spectroscopy after microwave digestion]. AB - Interest in atmospheric dry deposition results mostly from concerns about the effects of the deposited trace elements entering waterbody, soil and vegetation as well as their subsequent health effects. A microwave assisted digestion method followed by inductively coupled plasma mass spectrometric (MAD-ICP/MS) analysis was developed to determine the concentrations of a large number of trace metals in atmospheric dry deposition samples with a heavy matrix of polyurethane foam (PUF). A combination of HNO3-H2O2-HF was used for digestion. The experimental protocol for the microwave assisted digestion was established using two different SRMs (GBW 07401, Soil and GBW 08401, Coal fly ash). Subsequently, blanks and limits of detection for total trace metal concentrations were determined for PUF filter which was used for dry deposition sampling. Finally, the optimized digestion method was applied to real world atmospheric dry deposition samples collected at 10 sites in Jingjinji area in winter from Dec. 2007 to Feb. 2008. The results showed that the area-averaged total mass fluxes ranged between 85 and 912 mg x (m2 x d)(-1), and fluxes of most elements were highest at Baoding and lowest at Xinglong. In addition, the elemental fluxes in urban areas of Beijing, Tianjin and Tangshan were measured to be higher than that in suburb and rural sites. The average fluxes of crust elements (A1, Fe, Mn, K, Na, Ca and Mg) were one to three orders of magnitude higher than anthropogenic elements (Cu, Pb, Cr, Ni, V, Zn and Ba), varying from 151 to 16034 microg x (m2 x d)(-1) versus 14 to 243 microg x (m2 x d)(-1). Zinc was the most abundant heavy metal and calcium the highest of the crust elements while the elements Mo, Co, Cd, As and Be deposited less or even could not be detected. The anthropogenic and crustal contributions were estimated by employing enrichment factors (EF) calculated relative to the average crustal composition. The EF values of all elements except Pb and Zn were below 10, suggesting that local soil and/or dust generally dominate in the dry deposition flux. PMID- 20358808 TI - [Assessing PM10 and SO2 networks using positive matrix factorization in Beijing city]. AB - The aim of this study was to identify city areas with similar air pollution characteristics and determine which sites may be providing redundant information. Positive matrix factorization (PMF) was applied in this study to assess the mass concentrations of sulfur dioxide (SO2) and particulate matter with an aerodynamic diameter less than 10 microm (PM010), collected in the air quality monitoring network in the year of 2000. The analysis indicated that there were obviously seasonal variations for PM10 and SO2 in Beijing. The PM10 concentrations were higher in spring and lower in summer, but the SO2 concentrations were higher in winter and lower in summer. The results of the PMF showed that the sites of PM10 network in Beijing could be identified as three regions, which represented city areas characterized by the same specific air pollution. These three regions represented Gucheng site/Chegongzhuang site, Qianmen site/National Olympic Sports Center site/Tiantan site/Nongzhanguan site, and Ming Tombs site, respectively. Some sites in region 2 which included four sites may be redundant and can be removed. SO2 network can be divided into six regions including Chegongzhuang site/Qianmen site, Tiantan site/Nongzhanguan stie, Ming Tombs site, National Olympic Sports Center site, Dongsi site, and Gucheng site. It indicated that some sites in Beijing PM10 and SO2 monitoring networks might be redundant and could be removed or relocated to other areas. PMID- 20358809 TI - [Modeling the vehicle pollution in the urban streets before and during the Beijing Olympic Games traffic control period]. AB - In order to investigate the vehicle pollution situation in the streets in Beijing and the abatement during the Olympic Games, the OSPM model was applied to calculate the concentrations of PM10, CO, NO2 and O3 inside the urban streets of Beijing before and during the Olympic traffic controlling period in July, 2008. The modeled concentrations before the traffic control are 146 micog/m3, 3.83 mg/m3, 114.4 microg/m3 and 4.71 x 10(-1), while after the traffic control are 112 microg/m3, 3.16 mg/m3, 102.4 microg/m3 and 5.31 x 10(-9) , with the reduction rates of 23.4%, 20.5%, 10.5% and -12.5%, respectively. The research on these concentration changes and the daily variations of the pollutants reveals: the concentration of PM10 is most influenced by the traffic control; the concentration of CO presents the most similar daily variation with the traffic flow; the reduction of NO2 concentration is limited, indicating the influence of other factors other than the traffic emission; the concentration of O3 increases after the traffic control, which means the traffic management measures can not abate the O3 pollution in the street. Furthermore, the comparison between the calculation results in different types of street canyons reveals that the fleet composition and street geometry impact the concentration changes. In a word, the vehicle pollution inside the streets of Beijing before the traffic control is relatively serious, as the concentrations of PM10, CO and NO2, all approach or exceed the Grade II National Air Quality Standard; the traffic control measures take effect in reducing the primary pollutants, but the secondary pollutants may increase after the traffic control. PMID- 20358810 TI - [Effects of synoptic type on surface ozone pollution in Beijing]. AB - Ozone (O), influenced by meteorological factors, is a primary gaseous photochemical pollutant during summer to fall in Beijing' s urban ambient. Continuous monitoring during July to September in 2008 was carried out at four sites in Beijing. Analyzed with synoptic type, the results show that the ratios of pre-low cylonic (mainly Mongolia cyclone) and pre-high anticylonic to total weather conditions are about 42% and 20%, illustrating the high-and low-ozone episodes, respectively. At the pre-low cylonic conditions, high temperature, low humidity, mountain and valley winds caused by local circulation induce average hourly maximum ozone concentration (volume fraction) up to 102.2 x 10(-9), negative correlated with atmospheric pressure with a slope of -3.4 x 10(-9) Pa( 1). The time of mountain wind changed to valley wind dominates the diurnal time of maximum ozone, generally around 14:00. At the pre-high anticylonic conditions, low temperature, high humidity and systematic north wind induce average hourly maximum ozone concentration (volume fraction) only 49.3 x 10(-9), the diurnal time of maximum ozone is deferred by continuous north wind till about 16:00. The consistency of photochemical pollution in Beijing region shows that good correlation exists between synoptic type and ozone concentration. Therefore, getting an eye on the structure and evolution of synoptic type is of great significances for forecasting the photochemical pollution. PMID- 20358811 TI - [Indoor deposition flux and congener profiles of polybrominated diphenyl ethers (PBDEs) in Shanghai, China]. AB - Indoor dry deposition of eight homes and offices in the urban area of Shanghai, China were sampled with clean glass plate during July to August of 2008 to study the indoor deposition flux and congener profiles of polybrominated diphenyl ethers (PBDEs). 16 PBDEs congeners which including BDE-17, -28, -71, 47, -66, 77, -100, -99, -85, -118, -154, -153, -138, -183, -190 and BDE-209 were measured by GC-MS with negative chemical ionization (NCI) in selected ion monitoring (SIM) mode. The particulate deposition flux of PBDEs in homes and offices were (10.9 +/ 8.2) and (14.2 +/- 11.9) ng x (m2 x d)(-1) respectively. Deca-BDE (BDE-209) was the major compound, accounting for 88.2% -99.2% of the quantified PBDEs. The particulate deposition flux in the offices [(3.1 +/- 2.0) mg x (m2 x d)(-1)] was relatively lower than that of homes, but the concentration of PBDEs in the particles [(3361.6 +/- 1987.4) ng x g(-1)] was significantly higher than that of homes [(1169.1 +/- 647.1) ng x g(-1)]. The concentration of PBDEs in the indoor dry deposition of Shanghai ranked in the middle level comparing with other cities around the world. The indoor deposition flux of PBDEs was mainly correlated with the flux of particle deposition and the usage of electrical and electronic products, but not the interior decoration and the amount of furniture. PMID- 20358812 TI - [Distribution character of organochlorinated pesticides in the karst cavity atmosphere from Guilin City, south China]. AB - The investigation was performed on organochlorinated pesticides (OCPs) pollution in karst cavity atmosphere in Guilin City, South China. The total concentrations of OCPs outside the cave atmosphere ranged from 1.82 to 2.01 ng x m(-1), were far more than those of inside cave (range of 0.27-0.83 ng x m(-3)). OCPs concentrations fell gradually from cave gate to inside, especially to HCH, which reflected outside atmospheric transportation contributed most of pollutants inside cave. OCPs concentrations inside cave equaled to those in South and North poles therefore could be considered as background for OCPs research. The concentrations distribution sequence of HCH isomers corresponded to degradation rates themselves and that might provide critical information on the exhibiting their inherent character differences of HCH pesticides well under peculiarly original surrounding. In addition, a possibly fresh introduction of discofol-type and a historical usage potential for HCH pesticides in studied area were identified by isomer percentage combined isomer ratios. PMID- 20358813 TI - [Inhibition of sulfite oxidation catalyzed by heavy metals in dual alkali flue gas desulfurization slurry]. AB - Heavy metals accumulated in slurry of dual alkali flue gas desulfurization (FGD) present a significant catalysis to SO3(2-) oxidation, resulting in a waste of effective components for desulfurization. Na2S was adopted to precipitate heavy metal ions in FGD slurry, and the oxidation rate of SO3(2-) was obtained under different concentrations of heavy metal ions, to reveal the inhibition effect of Na2S on SO3(2-) oxidation catalyzed by heavy metal ions. Mn2+ showed a remarkable catalysis to SO3(-2) oxidation, as the initial oxidation rate of SO3(2-) was tripled to 0.65 mmol/(L x min) by adding 1.0 mmol/L Mn2+ into the slurry. SO3(2-) was catalytically oxidized rapidly with the reaction order 0.169 of Mn2+ within first 60 minutes, so it is of great importance to control the concentration of Mn2+ to inhibit SO3(2-) oxidation. At initial pH value of 6.50-8.50, Na2S removed heavy metal ions effectively from FGD slurry. Higher pH value favored the removal of heavy metal ions. The removal efficiencies of Mn2+, Zn2+, Ni2+ and Cd2+ were 91.0%, 88.1%, 85.5%, and above 99.9% respectively under the conditions of initial pH value 8.50 and Na2S dosage 240.0 mg/L. Mn2+ could be used as an indicator for the concentration of the heavy metal ions in the slurry. As the Mn2+ concentration decreased from 1.0 mmol/L to 5.0 x 10(-3) mmol/L by adding Na2S, the initial oxidation rate of SO3(2-) decreased by 64.6% to 0.23 mmol/(L x min). The desulfurization efficiencies increase 3.8%-5.1% by adding Na2S in a pilot scale setup. It comes to conclusion that heavy metal ions precipitation by adding Na2S with an indicator of Mn2+ to inhibit catalytic oxidation of SO3(2-) is feasible to reduce the consumption of desulfurizer in FGD slurry. PMID- 20358814 TI - [Depth profile of suspended particle scattering coefficient and its impact factors in Taihu Lake]. AB - To acquire the depth profile of suspended particle scattering coefficient and the mechanism of surface reflection, three different depths of Taihu Lake scattering coefficient and backscattering coefficient are obtained in Nov. 2008, respectively. And their characteristic variation with depth is studied. Profiling distribution of the slope of particulate size distribution (PSD) is computed by the attenuation coefficient. Profiling distribution of the concentration and composition of suspended particle is computed according the relationship between the scattering coefficient and the suspended particle concentration. Impact dominant factors on scattering coefficient of the depth of water are divided according to the range of refractive index. At the three depths (0, 50, 100 cm), the particle scattering, with the percentage 14%, 17%, 12% of the samples are dominated by algae, respectively. 35%, 30%, 34% of the samples are dominated by inorganic particulate matter and Non-algal organic particulate matter,and 51%, 53%, 51% of the samples are dominated by the above all. The results can be concluded as: scattering and backscattering coefficient of Taihu Lake water body changes with depth slightly. The concentration of total suspended particles is of more diversity in different lake area, but there is less difference at different depths except those samples near the inflow rivers. The main factors of scattering coefficient of most aquatic scattering in Taihu Lake had little difference at different depths, except several samples beside the inflow rivers. PMID- 20358815 TI - [Identification of spatio-temporal variation in the seaside water quality along Macau Peninsula]. AB - Cluster analysis (CA) and discriminant analysis (DA) were coupled to identify the spatial and temporal variation of the seaside water quality for 14 parameters and 22 different sites along Macau Peninsula, so as to identify the temporal and spatial variation for further optimizing the monitoring network and controlling the seaside water quality along Macau Peninsula. The results show that 12 months could be grouped into two periods, June-September and the remaining months, and the entire area was divided into two clusters, one located at western sides of Macau Peninsula, and another one is in southeast and southern sides of the Macau peninsula. Through backward stepwise DA, pH, Cl-, TSS, color and TP, Cl-, color, NH4+, DO, COD were identified as the discriminant variables of spatial and temporal variation, with 84.82% and 76.57% correct assignments, respectively. This study illustrates the application of multivariate statistical techniques is beneficial for understanding the temporal and spatial variation of seaside water quality and further effective water quality management. PMID- 20358816 TI - [Correlationships between the coverage of vegetation and the quality of groundwater in the lower reaches of the Tarim River]. AB - The variations vegetation coverage is the result of conjunct effects of inner and outer energy of the earth, however, the human activity always makes the coverage of vegetation change a lot. Based on the monitoring data of chemistry of groundwater and the coverage of vegetation from 2002 to 2007 in the lower reaches of Tarim River, relations between vegetation coverage and groundwater chemistry were studied. It is found that vegetation coverage at Sector A was more than 80%, and decreased from sector to sector, the coverage of Sector I was less than 10%. At the same sector, samples near to water source owned high coverage index, and samples far away from the river had low coverage index. The variations of pH in groundwater expressed similar regulation to vegetation coverage, that is, Sectors near the water source had higher pH index comparing than those far away. Regression between groundwater quality and vegetation coverage disclosed that the coverage of Populus euphratica climbed up along with increase of pH in groundwater, change of Tamarix ramosissima coverage expressed an opposite trend to the Populus euphratica with the same environmental factors. This phenomenon can interpret spatial distribution of Populus euphratica and Tamarix ramosissima in lower reaches of the Tarim River. PMID- 20358817 TI - [Characteristics and its forming mechanism on grain size distribution of suspended matter at Changjiang Estuary]. AB - In July of 2008, under the natural condition of sea water, the Laser in-situ scattering and transmissometry (LISST-100X Type C) was used to measure grain size distribution spectrum and volume concentration of total suspended matter in the sea water, including flocs at different layers of 24 sampling stations at Changjiang Estuary and its adjacent sea. The characteristics and its forming mechanism on grain size distribution of total suspended matter were analyzed based on the observation data of LISST-100X Type C, and combining with the temperature, salinity and turbidity of sea water, simultaneously observed by Alec AAQ1183. The observation data showed that the average median grain size of total suspended matter was about 4.69 phi in the whole measured sea area, and the characteristics of grain size distribution was relatively poor sorted, wide kurtosis, and basically symmetrical. The conclusion could be drawn that vertically average volume concentration decreased with the distance from the coastline, while median grain size had an increase trend with the distance, for example, at 31.0 degrees N section, the depth-average median grain size had been increased from 11 microm up to 60 microm. With the increasing of distance from the coast, the concentration of fine suspended sediment reduced distinctly, nevertheless some relatively big organic matter or big flocs appeared in quantity, so its grain size would rise. The observation data indicated that the effective density was ranged from 246 kg/m3 to 1334 kg/m, with average was 613 kg/m3. When the concentration of total suspended matter was relatively high, median grain size of total suspended matter increased with the water depth, while effective density decreased with the depth, because of the faster settling velocity and less effective density of large flocs that of small flocs. As for station 37 and 44, their correlation coefficients between effective density and median grain size were larger than 0.9. PMID- 20358818 TI - [Temporal distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons in sediment core from Miyun reservoir]. AB - The temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was measured in sediment core from Miyun reservoir, and the possible sources and the potential risk assessment also have been identified. The aim of the present work is to understand the temporal trend of PAHs in Miyun reservoir recently. The concentrations of sigma PAH16 in sediment ranged from 618.5 ng/g to 1087.9 ng/g, and roughly, increased continuously from the bottom (16 cm under the surface) to the surface sediment. The PAHs in sediment core were mainly composed of phenanthrene and fluorene. The concentrations of phenanthrene and fluorene in sediment core were 236.1-417.9 ng/g and 91-130.8 ng/g, respectively. Both of them accounted for 47.2%-58.1% of the sigma PAH16 in sediments. Nevertheless, high rings aromatic hydrocarbons (5-6 rings) were increased steadily in recent years. PAHs compositional profile indicated that the main source of PAHs was originated from the combustion of coal and biomass. However, the vertical profiles of Flu/Flu + Pyr and INP/INP + BghiP ratios suggested that the vehicles emission was increased very recently. Risk assessment suggested that PAHs in sediment from Miyun reservoir was no significant biological impairment, and low toxicological risk of PAHs was found up to now. PMID- 20358819 TI - [Characteristics of nitrogen cycling in farm systems in a small watershed of Three Gorges Reservoir Area, China]. AB - In China, the agricultural activities are often carried out by single family, and the balance of nitrogen in every farm may have great effect on agricultural production and environment. A farm survey was carried out on the amounts of chemical fertilizers consumed, the amounts of food and feed purchased, and the livestock manures used in Zhangjiachong watershed of Three Gorges Reservoir Area for each farmer. According to the characteristics of nitrogen flow, farms in this watershed could be divided into 5 types: breeding specialized farms, orange growing farms, tea-growing farms, vegetable-growing farms and traditional farms. Differences in environmental nitrogen load were observed among the five farm types in the following order: breeding specialized farms > vegetable-growing farms > orange-growing farms > tea-growing farms approximately = traditional farms, being (363 +/- 129), (355 +/- 127), (345 +/- 107), (152 +/- 60) and (151 +/- 73) kg x (hm2 x a)(-1) respectively by nitrogen. Nitrogen cycle for different farm fields showed that field surplus nitrogen ranged from (102 +/- 68) to (303 +/- 134) kg x (hm2 x a)(-1) among different farms. Among the five farm types, the field surplus nitrogen followed the order of vegetable-growing farms > citrus growing farms > tea-growing farms > breeding specialized farms approximately = traditional farms, being (303 +/- 134), (262 +/- 100), (111 +/- 46), (102 +/- 68) and (103 +/- 67) kg x (hm2 x a)(-1). The nitrogen from farm life activities accounted for 28% of the total N load, while the field surplus nitrogen was 72%. It was estimated that field nitrogen consumption was the predominated nitrogen pollution source in the watershed. However, the farmer's daily life pollution should not to be neglected. Breeding specialized farms, vegetable-growing farms and orange-growing farms were the high potential pollution sources for the water environment in the watershed, and the major attention should be paid to these types of farms. Field survey on farm nitrogen cycle is of significance in evaluating the nitrogen flows in the agro-ecosystems and revealing the characteristics of nitrogen cycling in the region. PMID- 20358820 TI - [Examination of silicate limitation of primary production by diatoms phytoplankton in the Daihai Lake]. AB - The Daihai Lake (40 degrees 29'27"-40 degrees 37'6"N, 112 degrees 33'31"-112 degrees 46'40"E) is a typical inland lake in a semiarid region in Inner Mongolia, China. Based on the geochemistry character of biogenic silica (BSi) in the water sediments system of the Daihai Lake, the theory of silicate limitation of Primary Production by Diatoms phytoplankton in the Daihai Lake are discussed in this work by interpreting the information of the BSi concentrations, horizontal and vertical distributions and the response relation between BSi and past environmental conditions. It is found that the concentration of Si is very low in overlying water while very high in the sediments. The spatial distribution patters of SiO3(2-) and BSi suggest the Si source of the lake. The geochemistry information of BSi is well archived in the lake sediment profiles, and the geochemistry information of BSi well responses to the past environmental conditions of the Daihai drainage basin. The ratios between Si, and C, N, P in the water-sediment system and the response relation between BSi and past environmental conditions indicate the main reasons for the theory of silicate limitation of Primary Production by Diatoms phytoplankton. Furthermore, the dominant factor for silicate limitation of Primary Production by Diatoms phytoplankton is different in different periods. PMID- 20358821 TI - [Treatment of Cr( VI) in deoxygenated simulated groundwater using nanoscale zero valent iron]. AB - Laboratory experiments and theoretical modeling studies were performed to investigate the mechanisms of Cr( VI) removal from deoxygenated simulated groundwater using nanoscale zero-valent iron, and to evaluate influencing factors and kinetics based on zeta potential, redox potential, ferrous concentrations, and the pe-pH diagram of Fe-Cr-H2O system. Experimental results demonstrate that the removal efficiency of Cr(VI) decreases with the increasing Cr( VI)/Fe mass ratio. When the Cr(VI)/Fe mass ratios are 0.025, 0.050, 0.075, and 0.100, the corresponding Cr(VI) removal rates are 100.0%, 85.6%, 72.7% and 39.6%, respectively. The Cr( VI) removal is favorable at acidic pH with fixed Cr(VI)/Fe mass ratio of 0.100. When pH are 3.0, 5.0, 7.0, 9.0 and 11.0, the Cr(VI) removal rates are 73.4%, 57.6%, 39.6%, 44.1%, and 41.2%, accordingly. The Cr(VI) removal follows the pseudo second-order kinetics. When pH is 7.0 and Cr(VI)/nZVI mass ratio is 0.025, the rate of Cr(VI) removal is the highest with rate constant at 9.76 x 10(-3) g x (mg x min)(-1). The conversion from Cr2O7(2-) to Cr3+ should be instantaneous when Cr2O7(2-) is absorbed on the surface of Fe. The Cr(VI) was reduced to Cr(III), which was subsequently incorporated into the FeOOH shell and formed a Cr-Fe film. The film once formed could further inhibit the electron transfer between Cr2O7(2-) and Fe. Then Cr(V) removal was primary controlled by the adsorption process. PMID- 20358822 TI - [Water quality model and its application in polluted river remediation by aeration]. AB - Aeration is a main method to remediate polluted river water. Based on Shanghai Xingang River's aeration remediation, theoretical polluted water quality model was built. At the same time, parameters identification and solution were defined. Compared with observation values, the results from the model showed that: the dissolved oxygen had an average relative error of 11.38%, of which the relative error less than 20% accounted for 83.3%; BOD, had an average relative error of 9.16%, of which the relative error less than 20% accounted for 91.7%; ammonia had an average relative error of 11.15%, of which the relative error less than 20% accounted for 91.7%. With the exception of the individual points, most of the values from this model had relative error less than 20%. This model could describe well Xingang River's water quality under aeration conditions. Aeration intensity, velocity, sediment suspension and temperature simulation were analyzed by this model, which provides theoretical calculation methods and the basis for engineering design and operation of polluted river aeration remediation. PMID- 20358823 TI - [Construction of a landscaping-type wetland system for wastewater treatment construction of a landscaping-type wetland system for wastewater treatment and analysis of plant denitrifying effect]. AB - A pilot landscaping-type wetland system for wastewater treatment was constructed by introduction of 15 selected ornamental plant species (including 4 terrestrial plant species). The pilot system consists of 2 sequenced treatment units and 12 sub-units, i.e., a primary treatment unit with 4 parallel cells and a secondary treatment unit with 8 subsurface flow cells. Designed experiments were conducted in the established system to investigate the characteristics of nitrogen accumulation in different plants and the contribution of plant nitrogen uptake to total nitrogen removal of the constructed wetland system. The result shows that the direct contribution by plant uptake to the total nitrogen removal is low, ca. 1%-3% within the nitrogen concentration range 37.5-55.6 mg/L in the influent. Plant uptake does not fully reflect the important role of the plant species in the constructed wetland system for wastewater treatment as the function of the plant should include further its interaction with microorganisms and wetland fillers by enhancing microbial activities and filler adsorption capacities. The plant denitrifying effect, defined as the difference in nitrogen removal rates between units with and without plants, has been used to represent the contribution in nitrogen removal due to presence of plant in the system. The plant denitrifying effect thus includes both the plant nitrogen uptake and the interaction effect of plant with microorganisms and wetland fillers, the later being found to account for more than 80% of the total nitrogen removal in the established treatment system. PMID- 20358824 TI - [Physiological character and the ratio of the sinking Microcystis in Lake Dianchi]. AB - Aimed to explore the relationship between Microcystis cells sinking and water bloom development, the physiological status of the sinking cells was characterized by comparing with the floating cells. The sinking ratio and the 3 [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) staining were also employed in surface and bottom samples to substantiate the character. The dynamics of the sinking ratio and the chlorophyll a concentration were also compared. The field Microcystis cells had relative stable positions in the sample container after 2 hours settlement in the lab. Statistic analysis suggested that the floating and the sinking colonies did not differ significantly on the indicators maximum quantum yield of PS II and membrane integrity (p > 0. 05), but did significantly on the electron transfer rate and nicotinamide adenine dinucleotide (phosphate), reduced disodium salt [ NAD (P) H] dependent oxidoreductase and dehydrogenase activities (p < 0.01). Furthermore, comparison between bottom samples and surface samples suggested the bottom had higher ratio of sinking and MTT negative cells (p < 0.01). These results implied that the sinking cells were injured and had lower metabolic activity. During the time from October 2007 to May 2008, the sinking ratio reached climax about 40% in winter, and a negative correlation between the sinking ratio and chlorophyll a concentration was observed (p < 0.05). Sinking played an important role in the decline of Microcystis bloom. A research on the sinking ratio will be helpful for the understanding of bloom development tendency. The characterization on the physiology status of sinking cells constructed basement for the introduction of sinking ratio to the prediction of water bloom development. PMID- 20358825 TI - [Effect of extracelluar organic matter and natural organic matter on coagulation]. AB - Influence of EOM and NOM on removal of algae and turbidity was investigated. The result showed that EOM had both beneficial and harmful effects on coagulation, it hindered the charge neutrality of the flocculant. Zeta potential of algae decreased from -40.6 mV to -14.7 mV, only when the modified chitosan was added above 0.2 mg x L(-1). But it became a coagulant aid when it combined with flocculant. The experiment indicated that turbidity removal would reach the peak efficiency (96%) with appropriate concentration of EOM (5.18 mg x L(-1)), therefore EOM would enhance the removal efficiency. NOM had the more negative effect on coagulation, the optimum removal efficiency of algae and turbidity decreased by 11% and 18% separately. Besides, the optimum dosage of modified chitosan increased from 0.35 mg x L(-1) and 0.1 mg x L(-1) to 0.7 mg x L(-1) and 0.3 mg x L(-1) respectively. So it is the key point to take advantage of EOM and remove the NOM in practice, as a result the flocculant loading will be decreased, the removal efficiency will be improved. PMID- 20358826 TI - [Study on preparation of composite nano-scale Fe3O4 for phosphorus control]. AB - Composite nano-scale Fe3O4 particles were prepared in sodium carboxymethyl cellulose (CMC) solution by the oxidation deposition method. The adsorptions of phosphorus by micro-scale Fe3O4 and composite nano-scale Fe3O4 were investigated in water and soil, and the role of cellulase in the adsorption of composite nano scale Fe3O4 was studied. Kinetic tests indicated that the equilibrium adsorption capacity of phosphorous on the composite nano-scale Fe3O4 (2.1 mg/g) was less than that of micro-scale Fe3O4 (3.2 mg/g). When cellulase was added to the solution of composite nano-scale Fe3O4 to degrade CMC, the removal rate of P by the nanoparticles (86%) was enhanced to the same level as the microparticles (90%). In the column tests, when the composite nano-scale Fe3O4 suspension was introduced in the downflow mode through the soil column, 72% of Fe3O4 penetrated through the soil bed under gravity. In contrast, the micro-scale Fe3O4 failed to pass through the soil column. The retention rate of P was 45% in the soil column when treated by the CMC-stabilized nanoparticles, in comparison with only 30% for the untreated soil column, however it could be improved to 74% in the soil column when treated by both the CMC-stabilized nanoparticles and cellulase, which degraded CMC after the nanoparticles were delivered into the soil. PMID- 20358827 TI - [Making optimal operation for a BNR process: modeling prediction and experimental verification]. AB - Based on the process model of a BNR system (BCFS), the effects of operational parameters on the effluent quality were predicted by modeling, and were testified simultaneously by a lab-scale experiment, from which almost the same results in the modeling and the experiment were obtained. This means that modeling can be realizably applied to make the optimal operation schemes regardless of pilot scale and/or full-scale experiments. Both the modeling and the experiment demonstrated that the bio-P removal performance was not influenced by the biomass amount in the anaerobic tank when the returned ratio (rA ) reached 1.5 and that rA had no significant correlation with COD and N removals. After the returned mixed liquor ratio (rB) increased over 2, the TN removal efficiency was not improved any more, and the COD and TP removals were not influenced by the variations of the rB. The returned mixed liquor ratio rC had almost no influences on the COD, TP and TN removals. Further, the COD and TP removals were not influenced when the dissolved oxygen (DO(R5)) in the aerobic tank was in the range of 1-2.5 mg x L(-1), but the effluent NH4+ -N increased over 1 mg x L(-1) when DO(R5 ) was below 2 mg x L(-1). So, the optimal operational parameters for the BCFS should be set at rA = 2, rB 2-2.5, rC = 0, DO(R5) 2-2.5 mg x L(-1). PMID- 20358828 TI - [Rapid startup and nitrogen removal characteristic of anaerobic ammonium oxidation reactor in packed bed biofilm reactor with suspended carrier]. AB - Packed bed biofilm reactor with suspended carrier was used to cultivate ANAMMOX bacteria with sludge inoculums from WWTP secondary settler. The startup of ANAMMOX reactor was comparatively studied using high nitrogen loading method and low nitrogen loading method with aerobically biofilmed on the carrier, and the nitrogen removal characteristic was further investigated. The results showed that the reactor could be started up successfully within 90 days using low nitrogen loading method, the removal efficiencies of ammonium and nitrite were nearly 100% and the TN removal efficiencywas over 75% , however, the high nitrogen loading method was proved unsuccessfully for startup of ANAMMOX reactor probably because of the inhibition effect of high concentration of ammonium and nitrite. The pH value of effluent was slightly higher than the influent and the pH value can be used as an indicator for the process of ANAMMOX reaction. The packed bed ANAMMOX reactor with suspended carrier showed good characteristics of high nitrogen loading and high removal efficiency, 100% of removal efficiency could be achieved when the influent ammonium and nitrite concentration was lower than 800 mg/L. PMID- 20358829 TI - [Coupling anaerobic baffled reactor and membrane-aerated biofilm reactor]. AB - Based on the consistent anaerobic status of outer layer of membrane-aerated biofilm reactor (MABR) and internal anaerobic baffled reactor (ABR), MABR and ABR were started up separately. The aerating membrane module was installed into a compartment of anaerobic baffled bioreactor to form the Hybrid MAB-ABR (HMABR). After the installation of membrane module, total COD and VFA concentrations in the HMABR effluent were deceased by 59.5% and 68.1% respectively, with increased nitrogenous pollutant remove efficiency by 83.5%, at influent COD concentration of 1600 mg/L and NH4+ -N concentration of 80 mg/L. When organic loading rate was increased by 50%, the effluent COD concentration was still below the level of 60 mg/L, indicating its good capability of counteracting influent organic loading fluctuation. Due to the decreased COD concentration and increased nitrate concentration in the third compartment after installing the membrane module, the biogas volume and methane contents in the third compartment were decreased, resulting in the steady and excellent effluent quality. In this hybrid process, the improved simultaneous removal of carbon and nitrogen for high-strength nitrogenous organic pollutants was realized in a single reactor. PMID- 20358830 TI - [Process characteristics of zeolite media biological aerated filter for treating aquaculture wastewater]. AB - In this study, an up-flow zeolite media biological aerated filter (ZBAF) was developed and employed for the treatment of aquaculture wastewater. The results showed that ZBAF could start up quickly after 7 d and 25 d in viewpoint of mineralization and nitrification. 0.25 m/h and 20:1 were found to be the optimal hydraulic loading and gas/water ratio, under which around 85% of COD and 70% of NH4+ -N were removed stably in the ZBAF. Through analysis of water quality and microorganism along the flow direction, the heterotrophic and nitrifying population occupied respectively in the bottom and top of the filter column, and lower DO concentration was regarded as the boundary zone for these two different groups of chemotrophic bacteria. The changing profiles of biomass (phospholipid P) and activity (oxygen uptake rate) showed the similar mode along the height of ZBAF, and their maximum values of 114.12 nmol/g and 0.67 mg/(g x h) were detected at the bottom of the filter. PMID- 20358831 TI - [Performance of a combined bio-chemical sulfidogenic system and microbial characteristics in the presence of H2]. AB - To study and evaluate the performance of the continuously-operated autohydrogenotrophic sulfate reduction technique enhanced with electrochemical method and to improve the sulfate removal efficiency, a combined bio-electrical sulfidogenic system was developed with a three-dimensional bio-cathode. Sulfate reduction rate was elevated markedly owing to H2 mass transfer enhancement, biomass augmentation and electrical field stimulation. Indeed, when a current of 0.50 mA was applied to the system, the average sulfate removal load was 1.94 g/(L x d) during the stable running status and the maximum removal load was 2.23 g/(L x d). Furthermore, the combined bio-electrical system was comparatively more stable in terms of response to the variation of influx load under the same hydraulic conditions. Results of SEM showed that besides the bacteria attached on the surface of the hollow fiber, large amount of biomass was aggregated on the surface and the inner gridding space of the graphite felt. PCR-DGGE analysis indicated that the diversity of the microbial community structure was slightly reduced resulting in an optimized one. The dominant genera were Desulfovibrio and Desulfomicrobium. Enhanced H2 mass transfer, biomass augmentation, optimized microbial community structure and electrical stimulation were the key important factors for the high sulfate reduction efficiency of the system. PMID- 20358832 TI - [CuO-Ru/Al2O3 catalytic ozonation of acetophenone in water]. AB - Two-component CuO-Ru based on active Al2O3 (CuO-Ru/Al2O3) catalyst was prepared by incipient wetness impregnation and used to catalytic ozonation of acetophenone (AP). The results showed that doping Ru could significantly improve the catalytic activity of CuO/Al2O3. For example, the COD removal rates of AP solution after 30 min by ozonation alone, CuO/Al2O3/O3, and CuO-Ru/Al2O3/O3 were 6.3%, 20.0% and 54.0%, respectively. The change of pH almost had no affect on degradation efficiency of AP. However, a comparison of COD removal between ozonation alone and catalytic ozonation indicated that CuO-Ru/Al2O3 catalyst was more suitable for application in neutral or acidic condition. CuO-Ru/Al2O3 catalyst could accelerate decomposition rate of ozone in water, and its decomposition rate constant reached 2.58 x 10(-3) s(-1) while that of ozone alone in double-water was 1.19 x 10(-3) s(-1). The experimental result of t-butanol indicated that CuO Ru/Al2O3 catalytic ozonation of AP followed a radical-type mechanism. PMID- 20358833 TI - [Non-dissociated species and dissociated species photodegradation and the rate constants prediction of phenolic compounds]. AB - Xe lamp was employed to simulate the sunlight as light source to study the direct photolysis of three kinds of phenolic pollutants under different pH values. The effects of the dissociation on their photolysis were investigated, and a calculation method and a forecasting model for the photolysis rate constants under the situation of dissociation and non-dissociation of phenolic pollutants were established. The experiment results showed that the photolysis rate constant of pentachlorophenol (PCP) increased from 25.30 x 10(-4) min(-1) to 82.90 x 10( 4) min(-1) when pH value varied from 4.0 to 9.0, and that of nitrophenol (PNP) decreased from 11.90 x 10(-4) min(-1) to 3.18 x 10(-4) min(-1) Similar to the PNP, the photolysis rate constant of phenol decreased from 32.50 x 10(-4) min(-1) to 13.40 x 10(-4) min(-1) with the pH value increased from 4.0 to 11.0. From analysis of the results, a power function relationships between the total photolysis rate constants (K) and dissociation degrees (alpha) of these three phenolic compounds could be established. If alpha had been determined, the dissociation and non-dissociation species photolysis rate constants could be calculated by the tangent equation of the power function. The effect of dissociation on the photolysis should be mainly attributed to the formation of the negative oxygen ions, which led to the changes of the activities of benzene ring and substituent groups. These results will provide theoretical references to further understand environmental behaviors of phenolic compounds in natural waters. PMID- 20358834 TI - [Analysis of methanogenic community of anaerobic granular sludge in a full-scale UASB treating avermectin wastewater]. AB - Methanogens is considered to be important functional microbial population in anaerobic granular sludge. Fluorescence in situ hybridization was used to analyze methanogens of anaerobic granular sludge in a full-scale UASB treating avermectin wastewater. The results indicated that the distribution forms of methanogens, Methanobacteriales and Methanosarcinales were identical on the surface and inner face of granular sludge samples in different formation stages (with different diameters) , although the relative abundances of these methanogens were different. The relative abundances of methanogens on the inner face were larger than these on the surface of granular sludge samples. The relative abundances of Methanobacteriales were larger than these of Methanosarcinales. The relative abundances of methanogens in all granular sludge samples ranged from (25.50 +/- 8.63)% to (48.67 +/- 8.87)%. The maximum relative abundances of methanogens were obtained in mature granular sludge with diameter of 1.0-2.0 mm, (47.08 +/- 8.26)% on the surface and (48.67 +/- 8.87)% on the inner face, respectively. The avermectin residue in wastewater showed possible inhibition effect on methanogens. The maximum specific methanogenic activities of granular sludge samples ranged from 1.311 to 1.562 g/(g x d), varying as same as COD removal ratios and relative abundances of methanogens, implying the strong correlation of methanogens with bioactivity of granular sludge. PMID- 20358835 TI - [Cu2+ biosorption by bacterial alginate extracted from aerobic granules and its mechanism investigation]. AB - The biosorption characteristic of copper ions onto dried Ca-alginate made of bacterial alginate extracted from aerobic granules was investigated in batch system. The biosorption rate of Cu2+ onto the alginate, effects of pH and alginate dosage on Cu2+ biosorption capacity and adsorption isotherm were analyzed. The biosorption of Cu2+ onto the dried Ca-alginate was a rapid process. The maximum Cu2+ uptake was 67.67 mg/g at pH 4, initial Cu2+ concentration of 100 mg/L, dried Ca-alginate dosage 0.7 g/L. Accumulation of Cu2+ followed Langmuir and Freundlich adsorption isotherm. Cu2+ adsorption was accompanied by Ca2+ releasing from the dried Ca-alginate and H+ uptake, indicating that the ion exchange between Cu2+ and Ca2+ requires H+ for charge balance. FT-IR secondary derivative spectra and atomic force microscopy analysis gave proof that, the reaction of MG blocks in dried Ca-alginate with Cu2+ and Ca+ were different. Cu2+ may form complex with MG blocks, leading to a much more ordered structure on the surface of the dried Ca-alginate. The dried Ca-alginate bio-adsorbent was regenerated by 100 mmol/L HCI with 91% Cu2+ recovery. PMID- 20358836 TI - [Densification of autotrophic bacteria sludge and its characteristics for wastewater treatment]. AB - Autotrophic granular sludge was developed in an SBR reactor using inorganic carbonal substrate. The variation of ammonia-oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) during the densification process and their effects on granulation have been evaluated. It was found that the autotrophic bacteria granular sludge was compact with the density reached up to 1.06 g/mL, and the rod like bacteria predominated in granules on the evidence of scanning electron microscopic (SEM) results. Ammonia, nitrite and nitrate in the effluent were 4.5 15.2 mg/L, 10.2-20.3 mg/L and 17.9-30.1 mg/L, respectively, and the ammonia removal efficiency was 78% -92%. By evaluating the profile of various types of nitrogen and their conversion rates, it was found that short settling time was the main factor that enriched the AOB at the beginning of this experiment, and the granulation did not correlate with AOB. On the contrary, nitrification rate well correlated with granulation, and evidence demonstrated that the formation of granulation was in favorate of immoblization of NOB and the metabolite of NOB stabilized granules, therefore granules and NOB mutually enhanced. Additionally, it was found that the autotrophic denitrification was gradually increased with the process of granulation. PMID- 20358837 TI - [Cultivation of aerobic granules by a method of alternative feed loading]. AB - The formation process and morphological and physicochemical properties of aerobic granules were examined in a SBR system by a method of alternative feed loading. The results showed that the aerobic granules could be quickly and effectively cultivated using the alternative feeding COD 400, 800, 1200 mg/L [feed loading 0.96, 1.92 and 3.84 kg/(m3 x d)] when other conditions were fixed. The developed granules of the reactor were maintained in MLSS 20-22 g/L and SVI 14-16 mL/g. The average size of completely granular particles was 613.6 microm in diameter. The cocci occupied mainly in outer layer of granules, and both cocci and rods existed in inner layer of particles. The granules reached 95% COD removal and 97% NH4+ -N removal simultaneously. The analysis of FISH showed AOB was distributed in outer surface of aerobic granules, and NOB existed in outer and inner layer small amounts of aerobic granules. PMID- 20358838 TI - [Characteristics of operational performance and membrane fouling in a sidestream membrane sequencing batch reactor with aerobic granule]. AB - The characteristics of operational performance and membrane fouling were investigated using synthetic wastewater as feed in a sidestream membrane sequencing batch reactor (MSBR) system. The experimental results showed that the average removal efficiencies of COD, TN, TP and NH4+ -N were 90%, 60%-80%, 80% and 95% respectively under the influent COD of 200 mg x L(-1) to 1200 mg x L(-1) during more than 150 days' operation. It was possible to achieve a complete granulation of sludge. In 70th day, sludge particles around 350 microm were detected more than 90%. From then, sludge grew up continuously and finally reached to 394 microm in diameter. With the formation of granular sludge in MSBR, the cleaning time of membrane system was prolonged to 65 days, which was larger than three times compared with flocculent sludge MSBR. It was also much better than conventional MBR. These results clearly demonstrated that the formation of granular sludge was good for improving the resistance to organic loading shock and retaining the membrane fouling of the system, and maintaining the stable operation for a long time. PMID- 20358839 TI - [Sludge performances and membrane pollution in aerobic granular sludge membrane bioreactor]. AB - The aerobic granular sludge membrane bioreactor worked for 75 days. In this operation, the removal efficiencies for COD, NH4+ -N and TN were 91%-95%, 89.57% 100% and 48.25%-90.84%, respectively. The granular sludge appeared disintegration to some extent and the sludge settlement performances deteriorated. Sludge specific resistance from initial resistance of 1.085 x 10(13) m/kg rose to 2.712 x 10(13) m/kg at the end; extracellular polymeric substances maintained between 44.71 and 72.23 mg/g. Then, pollution characteristics of the membrane module were studied. It was found that membrane surface cake layer resistance and membrane pore plugging resistance were 5.32 x 10(11) m(-1) and 2.34 x 10(11) m(-1), accounted for the total resistance of 67.42% and 29.66%, respectively. Through the analysis of infrared spectrum for membrane fouling matters found that the main fouling matters were proteins and carbohydrate materials for membrane. PMID- 20358840 TI - [Enhanced hydrolysis of excess sludge by external enzymes]. AB - The effects of external enzymes to enhance excess sludge hydrolysis were investigated. Protease and alpha-amylase were added singly and in combination, and it was found that external enzymes can enhance sludge hydrolysis. When treated with single enzyme, alpha-amylase had higher efficiency than protease, SCOD/TCOD rose from 16.3% to 22.3% and VSS reduction improved from 39.8% to 54.24% at the optimal dosage of 60 mg/g (calculated by addition of enzyme in TS). Furthermore, mixture enzymes showed better hydrolysis efficiency than single enzyme. The highest VSS reduction was observed at an enzyme mixture ratio of 1:3 with protease and amylase when the hydrolysis temperature was 50 degrees C, and the VSS reduction achieved 68.43%. Correspondingly, the concentration of reducing sugar and NH4+ -N rose from 37.29, 47.60 mg/L to 177.8, 143.43 mg/L, respectively. According to the kinetic and enzymatic analysis of hydrolysis process, sludge hydrolysis within prior 4 h was consistent with first-order reaction dynamic. During the hydrolysis, both protease and amylase activity rose gradually, the highest activity observed were 2.57 U/mL and 4.64 U/mL at 4h after hydrolysis. Thereafter, the enzyme activity decreased. PMID- 20358841 TI - [Analysis on heavy metal concentrations in agricultural soils of Baoshan, Shanghai]. AB - Based on the acquisition of heavy metal data from 216 topsoil samples of the agricultural land in Baoshan District, a typical region of Shanghai City, the content, distribution characteristics and sources of the heavy metals in agricultural soil of Shanghai Baoshan District were analyzed with the methods of combining multivariate statistics and geo-statistical. The results show that the average concentrations of the Cd, Hg, As, Cr, Pb, Cu and Zn in agricultural soil of Baoshan District are 0.195, 0.148, 7.44, 82.5, 29.1, 33.2 and 124.5 mg x kg( 1), they are lower than the secondary standards of the national soil environment; but the average concentrations of the Cd, Hg, Cr, Pb, Cu and Zn are more than background values of soil in Shanghai. Especially the Cd, Hg, Zn, they are 1.50, 1.48, 1.45 times higher than the background values, showing a net cumulative trend. The results of correlation analysis and factor analysis show that the sources of these elements can be divided into three categories; the Zn, Cd, Hg and Pb as one class; the Cr and Cu as another class; the As in a separate category. The concentrations of the former two classes are much higher than the background value, implying mainly from various human activities; the content of the As is almost the same as the background value of soil, it has the lowest degree of variation. Spatial structure analysis shows that the distribution of the As is influenced by the soil structural variations, such as soil parent material, topography, and other elements are mainly affected by random factors of human activities. Through the probability distribution of contour lines of the critical value, it can be found that the Cd, Zn, Cr, Cu, Hg come mainly from the point sources of pollution, but the source of Pb is relatively dispersed. PMID- 20358842 TI - [Reducing nutrients loss by plastic film covering chemical fertilizers]. AB - With the low utilization rate of fertilizers by crop and the growing amount of fertilizer usage,the agricultural non-point source pollution in China is becoming more and more serious. The field experiments planting corns were conducted, in which the applied chemical fertilizers were recovered with plastic film to realize the separation of fertilizers from rain water. In the experiments, the influences of different fertilizing treatments on the growing and production of sweet corn were observed. The fertilizer utilization rate and the nutrient contents in surface run-off water with and without the film covering were also determined. Results showed that, with only 70% of the normal amount of fertilizers,the sweet corn could already get high yield under the experimental soil conditions. Soil analysis after corn crops showed that the amounts of available N, P and K in the soil increased obviously with the film-covering, and the decreasing order was: 100% fertilizers with film-covering > 70% fertilizers with film-covering > 100% fertilizers, 70% fertilizers > no fertilizer. The average utilization coefficients of fertilizers by the crop were 42%-87%, 0%-3%, 5%-15% respectively for N, P and K. It was higher with film-covering than that without covering, especially for the high fertilization treatment. Analysis of water samples collected for eight run-off events showed that, without film covering, N, P and K average concentrations in the runoff waters with fertilizations were 27.72, 2.70 and 7.07 mg x L(-1), respectively. And they were reduced respectively by 39.54%, 28.05%, 43.74% with the film-covering. This can give significant benefits to the decrease of agricultural non-point source pollution and water eutrophication. PMID- 20358843 TI - [Effect of iron plaque on root surfaces on phosphorus uptake of two wetland plants]. AB - In situ micro-suction cups were used to collect samples of soil solution with Arundo donax Linn and Typha latifolia from defined segments at rhizosphere in field. The experiment was conducted to elucidate the contribution of iron plaque while wetland plants were used to remove phosphorus. The reddish iron plaque was observed and measured on the surfaces of roots of Arundo donax Linn and Typha latifolia in the field, 20,170.8 mg/kg (fresh weight) for Arundo donax Linn and 7640.3 mg/kg (fresh weight) for Typha latifolia were collected. Olsen-P contents of Arundo donax Linn with iron plaque were 28.85 mg/kg, 46.2% more than that of without, 34.99 mg/kg for Typha latifolia 21.9% more than that of without. The phosphate concentrations in the in situ rhizosphere soil solution of Arundo donax Linn with iron plaque were 0.65 mg/kg, 9.2% more than that of without, 0.56 mg/kg for Typha latifolia, 33.9% more than that of without. The phosphorus contents adsorbed by iron plaque were 81.7% for Arundo donax Linn and 85.7% for Typha latifolia of the wetland plants with iron plaque. Phosphate use efficiency of Arundo donax Linn with iron plaque was 16.5% more than that of without, 31.4% for Typha latifolia. The contents of phosphorus of single plant of the two wetland plants with iron plaque are higher than that of without. Due to adsorb phosphate with iron plaque, the transfer speeds of phosphate from non-rhizosphere to rhizosphere and from soil to soil solution are increasing. The phosphorus contents with iron plaque accumulated at rhizosphere and depleted at rhizosphere without iron plaque of Arundo donax Linn and Typha latifolia. PMID- 20358844 TI - [Effect of the melamine residue in soil on growth of Chinese cabbage]. AB - Soil and foliar application of melamine (ME) treatments to 'Zaoshu 5' Chinese cabbage were investigated. The ME was degraded very slowly in soil treated with different dosages (40,160 and 800 mg x kg(-1)), and 90 days later the residuals of ME were 21.1%, 15.8% and 43.6% respectively. The Chinese cabbage could take in exogenously applied ME through its root and stem leaf and accumulate it to considerable levels with the increasing applied density. In soil application test, the maximum and minimum contents of ME were 105.7 and 8.0 mg x kg(-1) in root, and 139.9 and 7.1 mg x kg(-1) in stem leaf; the ME transport occurred from root to stem leaf. In foliar application test,the maximum and minimum contents of ME were 4.3 and 0.9 mg x kg(-1) in root, and 8.5 and 3.2 mg x kg(-1) in stem leaf. In soil application test,the low level of ME (40 mg x kg(-1)) increased the biomass yield by 9.8% and the high level of ME (800 mg x kg(-1)) decreased the biomass yield by 15.9%; the contents of chlorophyll and soluble sugar increased,but the content of Vitamin C decreased. Foliar application ME had no obvious significance on the growth of Chinese cabbage. The studies indicate that the residual time of ME in soil is long and the Chinese cabbage can absorb exogenously applied ME and ME can affect the growth of Chinese cabbage. PMID- 20358845 TI - [Effect of napthalene on the DNA methylation patterns and level in rice (Oryza sativa L.)]. AB - In this study,two elite rice inbred lines, Nipponbare and Mastumae were selected and irrigated with naphthalene solution with different concentrations. Epigenetic instabilities in the blade of the plants in tillering and heading stage were assessed by MSAP marks. The results showed that naphthalene exposure induced epigenetic variations in all the samples based on different levels and patterns of DNA methylation. The changes of the percentage of 5-methylcytosine have no regulation. In total 1051 sites tested,the variation of 16.56 percentage of Nipponbare has significant difference compared with the variation of 12.08 percentage of Mastumae,which showed that the capability to resist naphthalene pollution was related to genotype and Mastumae was stronger than Nipponbare in the capability to resist naphthalene pollution. The variations of DNA methylation in different genotypes and different growth periods have significant differences. In general, the frequencies of demethylation (0.48%-10.41%) were higher than hypermethylation (0.10%-1.92%). We concluded that DNA demethylation might be one part of in plants mechanism to resist naphthalene pollution in plants. PMID- 20358847 TI - [Application of zebrafish microarray on the toxicity mechanism study of bisphenol A]. AB - The toxicity mechanism of bisphenol A (BPA) to zebrafish (Danio rerio) was studied in the molecular level,by the method of zebrafish microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Zebrafish embryos were exposed to 0.5, 1.5 and 4.5 mg/L BPA for 8 days since fertilization. The results from microarray and validated by qRT-PCR showed that, 50 specific genes were up-or down-regulated, and dose-responses for them were significant (p < 0.05). This study demonstrates the genotoxicity of BPA. Moreover,according to their function and pathway analysis,it could support the mechanisms for the morphological toxicity and metabolize turbulence observed in prophase study. PMID- 20358846 TI - [Effects of two organic pollutants on biomarker system of fish Lateolabrax japonicus and the pollution assessment]. AB - Responses of a select suite of protective enzymes in Lateolabrax japonicus including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (GSH) glutathione S-transferase (GST), nitric oxide synthase (iNOS) in liver tissue and brain acetylcholinesterase (AChE), which could work as sensitively biochemical biomarkers were analyzed when exposed to different concentrations of sodium dodecylbenzene sulfonate (SDBS) and benzo[a]pyrene (B[a]P) under controlled laboratory conditions. Results showed that: (1) The biochemical biomarkers included in this investigation, different responses occurred in the enzymatic activities when exposed to different pollutants: the activities of SOD, GST, Gpx and GSH content were significantly induced by B[a]P (p < 0.05) while others present little different as compared to the control. Differently, SDBS exposure greatly affected the activities of CAT, Gpx, iNOS and AChE while showed little effect on the other evaluated biomarkers. Gpx was the most sensitive biomarker that sensitively indicated the organic pollution stress. (2) The simultaneous assay on heat shock protein 70 (Hsp70) expression was conducted by flow cytometry (FCM) and result presented that Hsp 70 expression could be effectively induced by SDBS as compared to the control throughout the experiment; however, B[a]P obviously induced Hsp70 during the first 12 d and then decreased to the level of the control. (3) The evaluated method of biomarker system combined with principal component analysis (PCA) could effectively distinguish different pollutants under controlled laboratory conditions and might be a promising and warning method for the early assessment of environmental change exposed to different organic pollutions. PMID- 20358848 TI - [Isolation and characterization of a sulfate reducing Citrobacter sp. strain SR3]. AB - A sulfate reducing bacterium, designated strain 'SR3', was isolated from sludge of a sulfate-reducing up-flow anaerobic sludge bed (UASB) reactor for treating high concentration sulfate wastewater. It was identified as Citrobacter sp. based upon the phenotypic-characteristics and physiological properties as well as the analysis of the sequence of 16S rDNA. The strain could reduce sulfate under anaerobic and micro-aerobic conditions. The dissimilatory sulphite reductase gene (dsr) was also amplified from this strain's genomic DNA using specific dsr gene primers. In aerobic conditions, the strain couldn't reduce sulfate, but exhibited a highest growth rate. In anaerobic conditions, the optimal growth conditions for this stain were temperature 37 degrees C and initial pH 8.0. Under this conditions,the strain could reduced both SO4(2-) and Cr(VI) at initial Cr(VI) concentrations of 0.4-0.8 mmol synchronously. Its tolerance ability to Cr(VI) concentrations reaches 1.0 mmol. This is the first report about an facultative anaerobe with sulfate reducing function and dissimilatory sulphite reductase gene (dsr). PMID- 20358849 TI - [Isolation, identification and biodegradation characteristics of A new bacterial strain degrading BTEX]. AB - A bacterial strain, able to efficiently degrade benzene, toluene, ethyl benzene, and o-xylene ( BTEX) compounds, was isolated by acclimating and enriching the activated sludge from the aeration tank in refinery wastewater treatment plant using BTEX as the sole carbon source. Based on the morphological characteristics, physiological and biochemical characteristics, sequence analysis of 16S rDNA,and Biolog identification system,the isolate was identified as Mycobacterium cosmeticum which was a newly discovered species able to degrade BTEX. The optimal conditions for the growth of the strain were at 30 degrees C and pH 7.0. The order of BTEX degradation by this isolate is benzene,toluene, ethyl benzene,and o xylene. The specific oxygen utilization rates (SOUR) of the strain degrading benzene,toluene, ethyl benzene, and o-xylene were 165.3, 170.5, 49.3 and 57.4 mg x (min x mg)(-1), respectively. The degrading process of the strain followed the Haldane kinetic model. The maximum specific degradation rate degrading benzene, toluene, ethyl benzene,and o-xylene were 0.518, 0.491, 0.443 and 0.422 h(-1), respectively. Accordingly,the maximum specific growth rate 0.352, 0.278, 0.172 and 0.136 h(-1), respectively. PMID- 20358850 TI - [Isolation of a PHA producing strain with butyric acid as the carbon source and its shaking-flask fermentation character]. AB - A bacterial strain,WD-3,with high polyhydroxyalkanoates (PHA) yield was isolated from activated sludge. Its fermentation characters including the effects of C:N ratio, pH,fermentation time on the PHA production were also primary studied. The results showed that the optimal C/N ratio and pH were 35 and 7.0, respectively. PHA accumulation increased rapidly during the stable growth stage. The maximum PHA yield was 3.01 g x L(-), the strain accumulated PHA up to 45.4% of its cellular dry weight, and the proportion of PHV occupied one-third of the PHA production. Analysis of its 16S rRNA sequence showed that strain WD-3 belongs to Enterobacter. PMID- 20358851 TI - Toxoplasma: shutting the barn door after the horse ran off? PMID- 20358852 TI - [Atrioventricular septal defect characteristics in infants with and without Down's syndrome: a Lebanese study]. AB - OBJECTIVES: Analyze the demographic and clinical characteristics of complete atrioventricular septal defect (AVSD), its association with Down's syndrome, with other cardiac and extra-cardiac anomalies, and finally the impact of consanguineous marriages on the incidence of AVSD. PATIENTS & METHODS: The sample consisted of 2195 consecutive patients with congenital heart defect, entered in the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut, between Jan 1999 and Dec 2007. 120 patients with AVSD were analyzed. The gathered data included age, sex, type of AVSD, mother's age, 1st and 2nd degree cousins, and other associated cardiac or extra-cardiac anomalies. RESULTS: AVSD was diagnosed in 5.5% of all patients with congenital heart disease, with 81.7% (n = 98) being complete AVSD. Male sex was predominant (58%). More than half (57.5%) were also diagnosed with Down's syndrome. The mean maternal age was 30.4 years (+/- 4.7 years) and consanguinity found in 16.7% of the cases. Cardiac and extra-cardiac anomalies (all in the esophagus and intestine) were associated in 15% and 6.7% respectively. Complete AVSD was significantly associated with Down's syndrome: 94% of patients with Down's syndrome had a complete AVSD. Digestive anomalies were also significantly more frequent with Down's syndrome (10% versus 2%, p = 0.02). Other cardiac anomalies, however, were less frequent with Down's syndrome (33% versus 7.7%, p = 0.02). CONCLUSION: Down's syndrome is more frequently associated with isolated and complete AVSD. Other anomalies may complicate the management of these patients. The cause of this probable genetic anomaly is still debated. PMID- 20358853 TI - Seroprevalence of Toxoplasma antibodies among individuals tested at hospitals and private laboratories in Beirut. AB - Toxoplasmosis is a zoonotic disease of worldwide distribution. Infection with Toxoplasma gondii can result in debilitating disease especially in the immunocompromized host and pregnant women. Determination of its seroprevalence and risk factors have been studied in many countries as a mean to understand its epidemiology and implement control measures. The scarcity of information on T. gondii infection in Lebanon warranted studying the toxoplasma antibody findings among individuals tested at different hospitals and private laboratories in Beirut in order to have an insight on its current seroprevalence in this country. This is a retrospective study targeting information related to IgG and IgM anti T. gondii antibodies among females tested at different hospitals and private laboratories in Beirut. Toxoplasma antibody determination in the sera was done using different formats of semi-automated enzyme immunoassay techniques. The age of each tested individual was also recorded. The generated data was based on testing done at seven hospitals and seven private laboratories located in different areas of Beirut. The vast majority (around 96%) of the tested population were females with age ranging between 16 yrs and 40 yrs (i.e. mostly females at childbearing age). The seroprevalence of IgG anti-T. gondii antibodies determined on 1371 sera from hospital laboratories and 2145 sera from private laboratories were 55% and 67%, respectively. The IgM anti-T. gondii antibodies determined on 1352 sera from hospital laboratories and 2074 sera from private laboratories were 6.7% and 6.8%, respectively. Overall and among the 3516 and 3426 blood samples tested for toxoplasma IgG and IgM antibodies at all laboratories, the seropositivity was 62.2% and 6.8%, respectively. The toxoplasma IgG seropositivity showed significant (p<0.05) increasing correlation with advanced age, for example, from 9% at < or = 5 yrs to 78% at 46-50 yrs, and 94% at > or = 51 yrs. Based on this seroprevalence study, exposure to toxoplasm infection is considered high among the Lebanese population and it increases with advanced age. This current information reflects the endemicity of this disease and would help the medical and public health authorities to address policies for monitor and control aspects of the disease in Lebanon. PMID- 20358854 TI - [Body mass index and quantitative osseous ultrasonography of the phalanges in Lebanese post-menarcheal adolescent girls]. AB - AIM OF THE STUDY: To explore the relation between body mass index and phalanx ultrasound measurements in a group of Lebanese post-menarchal girls. METHODS AND RESULTS: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 168 post-menarchal girls aged 12-17 years using a DBM sonic bone profiler device. Anthropometrical characteristics (weight and height) were measured. Age and maturation index (years since menarche) were positively related to AD-SoS and BTT (p < 0.01). AD-SoS values were negatively related to BMI and body weight (r = -0,27; p < 0.001 and r = - 0,25; p < 0.001 respectively). There was no relation between BTT values and neither BMI nor body weight. Overweight girls (n = 36) had lower AD-SoS values than normal-weight girls (n = 122) (1994 +/- 87 m x sec(-1) vs 2041 +/- 82 m x sec(-1) respectively; p < 0.01). Obese girls (n = 10) had lower AD-SoS values than normal-weight girls (n = 122) (1976 +/- 96 m x sec(-1) vs 2041 +/- 82 m x sec(-1) respectively; p < 0.05). CONCLUSION: In this group of Lebanese post-menarchal girls, AD-SoS values are inversely correlated to BMI while BTT values were not related to BMI. PMID- 20358855 TI - The ultrasonographic prenatal diagnosis of conjoined twins. A case report. AB - Conjoined twins represent one of the rarest forms of twin gestation, occurring once in 30,000 to 100,000 births. This entity, if unnoticed early, implies major complication risks to the fetuses. We are reporting one case of conjoined thoracopagus twins diagnosed by ultrasonography at 19 weeks, thus emphasizing the role of ultrasound in early diagnosis, and decision on management of such a condition. PMID- 20358856 TI - Chronic pain: a review. AB - Chronic pain has been increasing in prevalence. It is considered the most underestimated health care problem impacting quality of life. A number of epidemiological studies conducted in different parts of the world, reported prevalence rates of chronic pain ranging from 12-80%. Chronic pain has detrimental effects on physical and mental health, daily activities, family relationships, employment, and economic well-being of the sufferers and family caregivers. Since the epidemiological studies about chronic pain in Lebanon are limited, the aim of this article is to help understand the magnitude of the problem and to depict strategies for the prevention and management of chronic pain. The article provides a review of the literature on the prevalence of chronic pain and the factors associated with it in adults. PMID- 20358857 TI - [The History of Medicine in Lebanon]. PMID- 20358858 TI - Michael Abraham Shadid: a Lebanese precursor of prepaid and cooperative medical care. PMID- 20358859 TI - Alzahrawy's management of fractures of the skull and spinal dislocations. PMID- 20358860 TI - Suturing methods and materials with special emphasis on the jaws of giant ants (an old-new surgical instrument). AB - The historical development of surgical sutures, ligatures, and staples is discussed. The use of the jaws of giant ants, especially in the suturing of bowel injuries, is documented. PMID- 20358861 TI - Strain diversity within Mycobacterium avium subspecies paratuberculosis--a review. AB - Mycobacterium avium subspecies paratuberculosis (MAP), is the etiological agent of Johne's disease (or paratuberculosis) in animals and has also been linked with Crohn's disease of human beings. Extreme fastidious nature of the organism (MAP) has hampered studies on diversity within the organism. Studies based on phenotypic properties like growth rate, pigmentation, lipid profile etc., are unable to provide complete information on diversity of MAP organism in nature. However, with the advent of molecular assays (IS900 RFLP, PFGE, IS1311 PCR-REA, SSR typing, VNTR typing etc.) in last 2 decades, progress has been made to differentiate MAP strains. MAP isolates have been classified into various types and subtypes using these molecular tools. Optimization of these typing assays has led to generation of new information about MAP strains, subtypes, their comparative genomics, relative evolution, comparative virulence etc. Knowledge of strain diversity is important for better understanding of molecular and sero epidemiology, infection and patho-biology, vaccine development and planning control strategies. The present review provides available information on MAP strains, ho st adaptations, their virulence,comparative genomics, relative genetic evolution and differentiation. PMID- 20358862 TI - Trans-differentiation of iris pigmented epithelial cells of Euphlyctis cyanophlyctis tadpoles into lens in vitro. AB - Meshed pigmented iris epithelium along with neural retina of tadpoles of the frog Euphlyctis cyanophlyctis were found to undergo dedifferentiation and subsequently transdifferentiate into lens in culture medium. During lag period, depigmentation (dedifferentiation) occurred in many cells. When culture became confluent 3-4 weeks after seeding tiny lens like structures differentiated from foci of cultured pigmented iris epithelium cells. The percentage of lens formation was higher in vitamin A treated cases. The culture system appears to be a suitable for investigating the changes occurred during trans-differentiation of pigmented epithelial cells into lens. PMID- 20358863 TI - Evaluation of effect of aqueous extract of Enicostemma littorale Blume in streptozotocin-induced type 1 diabetic rats. AB - The present investigation was undertaken to standardize and study the dose dependent effect of three weeks treatment with hot and cold aqueous extract of E. littorale (0.5, 1 and 2 g/kg, po) on streptozotocin (STZ) induced type I diabetic (confirmed by histopathology) rats (45 mg/kg, iv single dose). Treatment of rats with STZ produced cardinal signs of diabetes-mellitus like a significant loss of body weight, polyuria and polydipsia. There was also a significant increase in fasting blood glucose levels and AUC(glucose) associated with decrease in insulin levels and AUC(insulin) in STZ-diabetic rats. Treatment with E. littorale hot extract (1 and 2 g/kg) significantly reduced the elevated food intake and water intake, glucose and AUC(glucose) levels of diabetic rats. There was also a significant increase in serum cholesterol, serum triglyceride in the STZ diabetic rats. Treatment with E. littorale hot extract (1 and 2 g/kg) significantly decreased all these elevated levels in diabetic rats. Hot aqueous extract of E. littorale at 0.5 g/kg produced a significant decrease in serum glucose and triglycerides. At this doses serum cholesterol and AUC(glucose) were not found to be altered significantly.TLC finger-print profiles were established for the aqueous extract using HPTLC. Swertiamarin, which was used as a chemical marker, was found to be one of the major components in the hot extract while it was absent in cold extract. The results suggest that E. littorale possesses potential antidiabetic activity and improves lipid profile at a small dose of 0.5 g/kg. PMID- 20358864 TI - Rapamycin induces autophagy and exacerbates metabolism associated complications in a mouse model of type 1 diabetes. AB - Type 1 diabetes mellitus (T1DM) is characterized by lack of insulin production as a consequence of massive beta cells destruction. The contributions of autophagy to loss of beta cell mass were not clearly elucidated. Rapamycin is a specific and potent inhibitor of mammalian target of rapamycin (mTOR) and is used as the central immunosuppressant in T1DM patients especially for those who received islet transplantation. In the present study, effects of rapamycin on autophagy of T1DM were investigated in a mouse model treated with multiple low doses of streptozotocin. Rapamycin treatment led to hyperglycemia, weight loss, increased intake of food and drinking water, and islet inflammation in T1DM mice. Pathological changes including autophagy and apoptosis in pancreas, kidney, spleen and thymus, accompanied with an accumulation of LC3-II, Beclin1 and Caspase-3 protein were observed. The results indicate that rapamycin may exacerbate metabolism associated complications by activating autophagy and apoptosis in T1DM. PMID- 20358865 TI - Stem bark extraction of Ficus bengalensis Linn for anti-inflammatory and analgesic activity in animal models. AB - In the present study, anti-inflammatory and analgesic effect of aqueous extract of Ficus bengalensis (AEFB) and methanolic extract of F. bengalensis (MEFB) was evaluated in animal models. Preliminary results indicated that MEFB treatment possesses significant anti-inflammatory potential as compared to AEFB. The anti inflammatory activity of MEFB exhibited in both acute (carrageenan induced hind paw edema and acetic acid induced vascular permeability) and subchronic (cotton pellet-induced granuloma) models of inflammation was found to be significant. In addition, the extract also showed significant analgesic activity in acetic acid induced writhing. Pretreatment with MEFB during inflammatory condition (both acute and sub-chronic) prevented increase in malondialdehyde (MDA) formation and myeloperoxidase activity in edematous as well as granulomatous tissue. Further, serum marker enzymes (AST, ALT and ALP) increased in inflammatory conditions were also inhibited with MEFB treatment. Hence, the anti-inflammatory activity observed in the present study with MEFB could be attributed largely to its antioxidant and lysosomal membrane stabilizing effects. PMID- 20358866 TI - Antiallergic activity of Aristolochia bracteolata Lank in animal model. AB - Antiallergic activity of Aristolochia bracteolata was evaluated by using compound 48/80 induced anaphylaxis, dermatitis rhinitis and pruritus, as a preclinical model for acute phase of hypersensitivity reactions. The late phase hypersensitivity was evidenced by considering toluidine diisocyanate induced volume of bronchoalveolar fluid secretion and its inhibition. The possible antiallergic mechanism was evaluated by using compound 48/80 induced mast cell activation and estimated serum nitric oxide (NO), rat peritoneal fluid NO, bronchoalveolar fluid NO and blood histamine levels. The present study implied that the chloroform extract of Aristolochia bracteolata had potent and significant inhibitory effect on compound 48/80 induced pruritus and dermatitis activity in Swiss albino mice. It showed significant effect in toluidine diisocyanate induced rhinitis in swiss albino mice. Mast cell membrane stabilization activity was also observed in compound 48/80 induced mast cell activation. A significant reduction was observed in serum nitrate levels, rat peritoneal fluid nitrate levels and BAL nitrate levels. The extract was also found to possess significant inhibitory effect on blood histamine levels. It could be concluded that chloroform extract of A. bracteata possess potent antiallergic activity, possibly through mast cell membrane stabilization, inhibiting NO and histamine pathway. PMID- 20358867 TI - Adaptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm.f) Boj. in acute and chronic stress paradigms in rodents. AB - Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity. PMID- 20358869 TI - Production of bioemulsifier by Acinetobacter species isolated from healthy human skin. AB - Six Acinetobacter sp. isolated from healthy human skin were checked for the production of bioemulsifier. Optimization studies indicated that Luria Bertani broth pH 7 supplemented with calcium chloride (1%) was the optimum medium. Temperature at 37 degrees C was optimum and inducer oils in the medium did not enhance bioemulsifier production. Partial purification of bioemulsifier and chemical analysis revealed that it is a proteoglycan with protein (53%), polysaccharide (43%) and lipid (2%). Maximum emulsification activity obtained was 400 EU/ml. Thin layer chromatography revealed the presence of mannose and rhamnose sugar and oleic and palmitic acids as parts of lipids. The yield obtained was 1.9 g / 1. Reconstitution studies revealed that the protein and polysaccharide fractions together display 94.55% of emulsification activity. It was also noted that the bioemulsifier was stable for 72 hr at 37 degrees C and displayed good cleaning property towards different oils. The partially purified bioemulsifier formed stable oil-in-water emulsions with plant oils. PMID- 20358868 TI - Role of glucagon-like peptide- 1 in vascular endothelial dysfunction. AB - The present study has been undertaken to investigate the effect of exendin-4 (a glucagon-like peptide-1 agonist) in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg-1, iv, once) and methionine (1.7% w/w, po, 4 weeks) were administered to rats to produce DM (serum glucose >200 mg d1-1) and HHcy (serum homocysteine >10 microM) respectively. VED was assessed using isolated aortic ring preparation, microscopy of thoracic aorta, and serum nitrite/nitrate concentration. Serum TBARS concentration was estimated to assess oxidative stress. Atorvastatin has been employed as standard agent. Exendin-4 (1 microg kg 1, ip) and atorvastatin (30 mg kg-1, po) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Exendin-4 and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine-induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. However, this ameliorative effect of exendin-4 has been prevented by L NAME (25 mg kg-1, ip), an inhibitor of NOS. It may be concluded that exendin-4 may activate eNOS due to activation of GLP-1 and consequently reduce oxidative stress to improve vascular endothelial dysfunction. PMID- 20358870 TI - Wheat (Triticum aestivum) peptide (s) mimic gibberellin action and regulate stomatal opening. AB - Wheat peptides (0.5 to 3 KDa M(r)) mimick hormonal activity like that of gibberellins and forced open dark closed stomata. The deionized amphoteric peptides solution after passing through cation and anion exchanger resins was run through Amicon's ultrafilters, 10, 3 and 0.5 kDa (M(r)) cut off system. The 3 to 0.5 kDa fraction passed through sephadex LH-20 column and collected in 140 tubes (5 ml in each tube). The two fractions F 9 (91-100 tubes) and F 12 (121-130) were found much active on stomatal opening and a-amylase activity, respectively and were ninhydrin positive. Capillary electrophoresis of F 9 fraction yielded several peptides ranging 1600 to 2200 (M(r) and F 12 fraction showed 1800 - 2800(M(r)). Both the fractions were totally hydrolysed for amino acid analysis by HPLC. Most of the amino acids were present except cystein in both the fractions. The F 9 fraction, (peptide present in 10 microg fresh wt tissue per ml) induced the dark grown closed stomata to open upto 70%. In F 12 fraction, (peptide present in 10 microg fresh wt equivalent tissue per ml) showed alpha-amylase induction which was much higher than GA(3) (10(9) M). The peptide might be present in membrane and bound with GA that activated alpha-amylase m-RNA synthesis. The peptide might act directly on alpha-amylase gene. PMID- 20358871 TI - Screening and partial immunochemical characterization of sulfite oxidase from plant source. AB - Sulfite oxidase [SO; EC 1.8.3.1] catalyses the physiologically vital oxidation of sulfite to sulfate, the terminal reaction in degradation of sulfur containing amino acids, cysteine and methionine. Sulfite oxidase from vertebrate sources is among the best studied molybdenum enzymes. Existence of SO in plants has been established recently by identification of a cDNA from Arabidopsis thaliana encoding a functional SO. The present study was undertaken to identify herbaceous and woody plants (viz., Azardirachta indica L., Cassia fistula L., Saraca indica L., Spinacea oleracea L., and Syzyzium cumini L.), a relatively less explored source, having significant SO activity and to characterize some of its immuno biochemical properties. The Syzyzium cumini was chosen to characterize SO as it showed maximum enzyme activity in the crude extract as compared to other plants. Absorption spectra of SO revealed two peaks at 235 and 277 nm, but no distinct peak in the visible region could be observed. Crude extract of all the plants were taken into considerations for immuno-biochemical studies. Despite of significant protein structure-functional similarities between plant and animal SO, no cross-reactivity could be established between the two sources of SO. These data suggested that plants SO, however, differed with regards to their immunobiochemical properties. PMID- 20358872 TI - We have not heard reform's swan song. PMID- 20358873 TI - Strategies for dealing with the national coding shortage. AB - Steps providers should consider to deal with a national coding shortage and implementation of ICD-10 include the following: Concentrate on employee retention (consider retention bonuses; upgrade pay scales; and offer flex-time and flexible work schedules). Begin a training program for ICD-10. Target other healthcare professionals and current employees to transition into coding positions. Collaborate with colleges, high schools, and middle schools to draw prospective students to this career path and your organization. PMID- 20358874 TI - Payment change: 3 ways to set your course for success. AB - Healthcare organizations can take three approaches to preparing for significantly slower spending growth: Reflect on lessons learned from past spending cuts. Chart their course for the payment reform journey. Learn from early adopters: accountable care organizations. PMID- 20358875 TI - Squeezing the funding you need from today's capital sources. AB - Healthcare providers need to understand traditional and nontraditional financing options and other potential strategies for accessing capital. Common financing options include bonds, commercial lending, acquisition financing, and financing through the Department of Housing and Urban Development's Section 232 program. Alternative strategies for accessing capital include joint ventures, equity, sale of assets, fund-raising, capital leases, internal capital, public grants, and grants from foundations. PMID- 20358876 TI - Capitalizing hidden values from hospital assets. AB - Benefits from selling noncore assets include generating capital and freeing up management resources. Monetization transaction structures include sale, partnership, and strategic affiliation. A hospital that engages in such a transaction needs to ensure that the purchaser or joint venture partner will maintain the hospital's high standards of care and ethical principles. PMID- 20358877 TI - Access to capital: implications for hospital consolidation. AB - Recent economic challenges have left many independent hospitals and their boards concerned about long-term viability of their organizations as stand-alone facilities. The CFO's role should be to facilitate a candid, objective assessment of the organization's ability to continue to go it alone. Key indicators that should be considered in such an assessment include patient volume, degree of physician alignment, profitability, current debt burden, cash, available capital versus capital requirements, and credit rating changes. PMID- 20358878 TI - Are alternative investments the right approach for your organization? AB - The decision by a healthcare provider to implement and monitor an alternative investment program requires careful consideration and planning. There are several things an organization should do when making this decision: Begin slowly. Consider access and liquidity. Don't force the investment to fill a target allocation. View an alternative investment as an opportunity investment." PMID- 20358879 TI - Culture clash: aligning payers and providers for real reform. AB - Self-imposed cost containment is not part of providers' heritage. The payer business model and its problems are complicated; simplistic reforms won't help. Health reform needs to be refocused on policies that allow providers and payers to align their cultures so that all parties benefit from potential synergies to provide top-quality care as inexpensively as possible. PMID- 20358880 TI - A Form 990 Schedule H conundrum: how much of your bad debt might be charity? AB - IRS Form 990 Schedule H requires hospitals to estimate the amount of bad debt expense attributable to patients eligible for charity under the hospital's charity care policy. Responses to Schedule H, Part III.A.3 open up the entire patient collection process to examination by the IRS, state officials, and the public. Using predictive analytics can help hospitals efficiently identify charity-eligible patients when answering Part III.A.3. PMID- 20358881 TI - Recovering FICA tax paid on resident stipends: 2010 update. AB - Recently, the IRS announced that it would cease contesting timely filed refund claims for taxable quarters before April 1, 2005, although the details that apply to its processing of those claims were not available as this article went to press. The IRS will continue to contest refund claims filed for taxable quarters after March 31, 2005, so those claims will have to be litigated to a conclusion. Financial officials at teaching hospitals should consult with advisers who are knowledgeable about the litigation against, and the settlement practices of, the Department of Justice. PMID- 20358882 TI - CFOs should be engaged with an EHR initiative. PMID- 20358883 TI - Why a detailed IT plan should be part of your organization's strategy. PMID- 20358884 TI - What would you do? Primary care growth at any cost? PMID- 20358885 TI - Capital allocation and risk mitigation. PMID- 20358886 TI - Decoration of carbon nanotubes with metal nanoparticles by wet chemical method: a small-angle neutron scattering study. AB - Multi-wall carbon nanotubes have been synthesized by catalytic chemical vapour deposition method. Attempts have been made to decorate the walls of these nanotubes with various metal nanoparticles (Ni, Cu and Fe) after functionalizing the nanotubes walls by wet chemical method. Small-Angle Neutron Scattering data reveals chain cluster type morphology of the carbon nanotubes. Transmission electron microscopy, Energy dispersive analysis of X-rays and Small-Angle Neutron Scattering measurements show that decoration of nanotube walls by metallic nano particles could be realized for Ni and Cu nano-particles. Further, wall decoration by nano-particles of Fe could not be achieved by wet chemical method due to strong agglomeration behavior of Fe nano-particles. PMID- 20358887 TI - Marine fouling release silicone/carbon nanotube nanocomposite coatings: on the importance of the nanotube dispersion state. AB - The present work reports on the influence of the dispersion quality of multiwall carbon nanotubes (MWCNTs) in a silicone matrix on the marine fouling-release performance of the resulting nanocomposite coatings. A first set of coatings filled with different nanofiller contents was prepared by the dilution of a silicone/MWCNTs masterbatch within a hydrosilylation-curing polydimethylsiloxane resin. The fouling-release properties of the nanocomposite coatings were studied through laboratory assays with the marine alga (seaweed) Ulva, a common fouling species. As reported previously (see Ref. [19]), the addition of a small (0.05%) amount of carbon nanotubes substantially improves the fouling-release properties of the silicone matrix. This paper shows that this improvement is dependent on the amount of filler, with a maximum obtained with 0.1 wt% of multiwall carbon nanotubes (MWCNTs). The method of dispersion of carbon nanotubes in the silicone matrix is also shown to significantly (p = 0.05) influence the fouling-release properties of the coatings. Dispersing 0.1% MWCNTs using the masterbatch approach yielded coatings with circa 40% improved fouling-release properties over those where MWCNTs were dispersed directly in the polymeric matrix. This improvement is directly related to the state of nanofiller dispersion within the cross-linked silicone coating. PMID- 20358888 TI - Magnetic properties of Fe(x)Pt(y)Au(100-x-y) nanoparticles. AB - Fe(x)Pt(y)Au(100-x-y) nanoparticles of size 3.5 nm were prepared by polyol reduction of platinum acetylacetonate and gold acetate and the thermal decomposition of iron pentacarbonyl. The as-synthesized nanoparticles with disordered fcc structure were then heat treated to transform to the L1(0) structure with high magnetocrystalline anisotropy. By tuning the stoichiometry of the Fe(x)Pt(y)Au(100-x-y) nanoparticles, the phase transition temperature was reduced by more than 200 degrees C. After the annealing 500 degrees C, for instance, the highest coercivity of 18 kOe was obtained from the Fe51Pt36Au13 nanoparticles which is substantially higher compared to 2 kOe for Fe51Pt49 nanoparticles annealed at the same temperature. In addition to the high coercivity, the saturation magnetization value obtained from Fe51Pt36Au13 nanoparticles was 47 emu/g which is similar to that for the Fe51Pt49 nanoparticles, indicating that there is no trade-off between the coercivity and the saturation magnetization upon Au doping. PMID- 20358889 TI - Coordination of graphene oxide with Fe3O4 nanoparticles and its enhanced optical limiting property. AB - A graphene oxide-Fe3O4 (GO-Fe3O4) hybrid material was prepared by a simple chemical precipitation method. The formation of this hybrid material was verified by Fourier transform infrared spectroscopy, high resolution transmission electron microscopy and X-ray powder diffraction. The optical limiting performance of this hybrid material was studied using the Z-scan measurement, which shows a much enhanced optical limiting performance compared with GO and is comparable with the benchmark material-C60. The mechanism responsible for this enhancement may be attributed to the enhanced nonlinear scattering effect introduced by the Fe3O4 nanoparticles. PMID- 20358890 TI - An efficient strategy for sequencing-by-synthesis. AB - Currently, the products of polymerase chain reaction (PCR) provide the templates for most of sequencing methods. RCA is a method for amplifying DNA. We report an approach for preparing sequencing templates based on rolling-circle amplification (RCA) to reduce the cost of sequencing when compared to the cost of conducting PCR. We describe a method using modified slides: acrylamide-modified slides, streptavidin-modified slides and aldehyde-modified slides. The products of RCA can be immobilized onto an acryl-modified slide surface. The Cy5-labeled deoxyribonucleoside triphosphate (dNTP) species are incorporated in extension reactions which can be read by determining the level of fluorescence. Then the fluorescence is deactivated using hydrogen peroxide (H2O2) as one of the oxidants. With the fluorescence deactivated, further extension and reading along the DNA chain is possible. Using this method, we successfully read a sequence of 27 bases. This strategy shows potential as a next-generation sequencing method. PMID- 20358891 TI - Mechanical characteristics of silicon nanostructures using force distance spectroscopy. AB - Experimental studies were undertaken to determine mechanical stiffness of Si chevron nanostructures grown by glancing angle deposition. Atomic force microscope based force-distance spectroscopy was performed on two types of chevron structures. The average stiffness of four-armed chevrons was found to be 381 +/- 16 Nm(-1), while that of five-armed chevrons was determined to be 375 +/- 23 Nm(-1). Simulations using finite element modeling were carried out to understand the mechanical characteristics of chevrons. For the nanostructures investigated in the present study, the simulation results indicate that while five-armed chevrons behave as springs, the four-armed chevrons act as cantilevers. It is shown that the position of loading point, physical dimensions and the geometry of the chevron control the overall mechanical response of chevron structures when subjected to an external load. It is proposed that by controlling the deposition parameters in glancing angle deposition, the topography of the structures and hence the position of loading points can be manipulated to generate a desirable mechanical response. PMID- 20358892 TI - Realization and manipulation of ZnO nanorod arrays on sapphire substrates using a catalyst-free metalorganic chemical vapor deposition technique. AB - Single-crystalline ZnO nanorod arrays (ZNRs) were grown by metalorganic chemical vapor deposition on ZnO buffer/sapphire substrate without using any metal catalyst. The density of vertically aligned ZNRs was found to govern by the morphology and thickness of buffer layer. That is to say, the ZnO buffer layer can be used as the nucleation template to control the growth direction and density of the ZNRs. In addition, by controlling the diethyl zinc flow rate, we can manipulate the size, crystal, and optical quality of ZNRs. Finally, the possible growth mechanism of ZNRs was discussed in detail. PMID- 20358893 TI - Molecular architecture of thin films fabricated via physical vapor deposition and containing a poly(azo)urethane. AB - Organic thin films are widely applied as transducers in devices whose performance is determined by the optical and electrical properties of the films. In this context, the molecular architecture of the thin films plays an important role. In this work we report the fabrication and characterization of a poly(azo)urethane synthesized fixing CO2 in bis-epoxide followed by a copolymerization reaction with an azodiamine without using isocyanate. The poly(azo)urethane thin films were fabricated by physical vapor deposition (PVD) technique using vacuum thermal evaporation. The molecular architecture of the PVD films was investigated under control growth at nanometer level of thickness, as well as the surface morphology at micro and nanometer scales and the molecular organization. The thermal stability of the poly(azo)urethane molecules, which is a challenge in itself considering the thermal evaporation process, was followed by thermogravimetric analysis (TG) and also by both Fourier transform infrared absorption (FTIR) and ultraviolet-visible (UV-vis) absorption spectroscopies. The UV-vis absorption spectra showed a linear growth of the absorbance of the PVD films with the mass thickness measured by a quartz crystal balance. A random distribution of the poly(azo)urethane molecules in the PVD films was revealed by FTIR spectra. The film morphology was investigated at microscopic level combining chemical and topographical information through micro-Raman technique. At nanoscopic scale, the morphology was investigated by atomic force microscopy (AFM) for films fabricated using distinct evaporation rates. As a proof of principle (for potential applications), the film luminescence was measured over a wide range of temperature. Interestingly, an unusual increase of fluorescence intensity was observed at +150 degrees C after a monotonic decrease from -150 degrees C. PMID- 20358894 TI - Influence of fillers on NR/SBR blends containing ENR-organoclay nanocomposites: morphology and wear. AB - In this study the Epoxidized natural rubber (ENR) and Organoclay (Cloisite 20A) were prepared by solution mixing process. The obtained nanocomposites were incorporated in Natural rubber (NR) and Styrene butadiene rubber (SBR) blends in presence of varying types of carbon black as reinforcing fillers. Morphology, curing characteristics, mechanical and thermal properties were characterized and analyzed. Also, the wear characteristics of the nanocomposites against Du-Pont abrader, DIN abrader and different mining rock surfaces were determined and discussed. The morphology of the organoclay incorporated in ENR shows a highly intercalated structure. ISAF type of carbon black shows a significant effect on curing and mechanical properties by reacting at the interface between SBR and NR matrix. All the samples show only one melting peak at same temperature on the DSC curve. Blends containing ISAF N234 type of carbon black shows high abrasion resistant properties against Du-Pont abrader, DIN abrader and different mining rock. The rubber compound containing 70 wt% of NR, 30 wt% of SBR and 10 wt% of ENR/nanoclay with ISAF N231 are found to be the toughest rubber against all types of rock under the present study. PMID- 20358895 TI - Strong surface plasmon resonance of ordered gold nanorod array fabricated in porous anodic alumina template. AB - High-density, uniform-sized and vertically aligned gold nanorods were grown on aluminum substrate by DC electrodeposition into modified porous anodic alumina (PAA) template. Optical reflection measurements using s- and p-polarized light showed strong surface plasmon resonances (SPRs), for both Au/PAA composites and freestanding Au nanorod arrays. By changing the aspect ratio of the Au nanorods, the angle of incidence of the polarized light, and the dielectric environment, it was possible to vary the position and the intensity of the SPR reflection minima in a reproducible and predictable manner. We successfully measured higher order transverse SPR, which proves the formation of highly uniform Au nanorods. PMID- 20358896 TI - Nano-inspired fibrous matrix with bi-phasic release of proteins. AB - Nanofibrous matrix was fabricated for the purpose of obtaining bi-phasic protein releases from a single protein delivery system. A block copolymer composed of poly(ethylene glycol) and poly(epsilon-caprolactone) was co-electrospun with protein solutions through a dual nozzle electrospinning system. Surface-exposed amine groups of the protein-encapsulating nanofiber at an aqueous phase were chemically conjugated to the carboxyl groups of another protein for surface immobilization. The surface-immobilized proteins and the core-encapsulated proteins in the nanofibers were characterized by scanning electron microscopy and confocal microscopy. Encapsulation efficiency of protein in the core of the nanofiber was increased when poly(vinyl alcohol) was mixed in the protein solution. Flow rate ratios of protein solutions to polymeric solutions significantly affected encapsulation efficiency of proteins in the nanofiber, where high flow rate ratios increased encapsulation efficiencies of proteins in the nanofiber. Release profiles of the immobilized proteins and the encapsulated proteins from the nanofiber were examined for 4 days. The encapsulated proteins showed initial burst profiles while the surface-immobilized proteins showed no or minimal release of proteins for the release period. Thus, the nano-inspired fibrous matrix can be potentially employed to fabricate a drug delivery device with a bi-phasic release profile of proteins. PMID- 20358897 TI - Synthesis of beta-SiC/SiO2 core-sheath nanowires by CVD technique using Ni as catalyst. AB - Cubic silicon carbide (beta-SiC)/SiO2 nanowires with uniform and knotted-core structures have been synthesized on nickel-coated Si(111) substrates at 1150 degrees C by using hexamethyldisilane (HMDS) as the source material in a hot wall atmospheric pressure chemical vapor deposition (APCVD) system. The nanowires consist of a single crystalline beta-SiC core wrapped with an amorphous SiO2 shell. The as-prepared SiC nanowires and the deposited Ni films were characterized by field emission scanning electron microscopy, X-ray diffraction, high resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, infrared spectroscopy and atomic force microscopy. The results show that the nanowires are random in direction and have diameter ranges from 25 nm to 70 nm. The core of the nanowires has a cubic zinc blend structure and a high density of planar defects is often found. The twin plane defects are suspected to be the main reason for the formation of the knotted-core SiC nanowires. A possible growth mechanism based on vapor-liquid solid (VLS) by base growth technique is proposed. PMID- 20358898 TI - Chemical synthesis of monodisperse Fe-Ni nanoparticles via a diffusion-based approach. AB - We report a chemical route for the preparation of monodisperse Fe-Ni nanoparticles with tunable compositions and sizes. Unlike commonly used synthetic approaches that involve the simultaneous reduction of metal precursors in the presence of reducing agents, the approach developed in this study utilizes pre formed Ni nanoparticles to react with Fe(III) acetylacetonate in high boiling point solvents, wherein newly-generated Fe atoms diffuse into Ni nanoparticles to form Fe-Ni nanoparticles. The analytic results of powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) show that the as-synthesized Fe-Ni nanoparticles possess a face-centered cubic (fcc) crystalline structure and have a spherical or near-spherical morphology. X-ray photoelectron spectroscopy (XPS) study reveals metallic characteristics for the chemical state of Fe and Ni. The particle morphology and size distribution of the as-synthesized Fe-Ni nanoparticles are regulated by the pre-formed Ni nanoparticles, while the composition can be adjusted to some extent by the ratio of Fe precursor to Ni nanoparticles. Magnetic measurements reveal a superparamagnetic characteristic above the blocking temperature for the as-synthesized Fe-Ni nanoparticles. The synthetic approach may also be applied to other bimetallic nanoparticle systems. PMID- 20358899 TI - Synthesis and characterization of phthalic europium(III) fluorescent complex nanorods. AB - The rare earth ion europium(III) was chosen as the central fluorescent ion, and phthalic acid (H2L) was chosen as the ligand. The rod-like phthalic europium(III) fluorescent complex was synthesized using a co-precipitation method in a polyvinylpyrrolidone (PVP) aqueous medium. The chemical composition of the synthesized complex was speculated to be PVP/Eu2L3 x 3H2O by elemental analysis, inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and Fourier transform infrared spectroscopy (FT-IR). The X-ray diffraction analytic (XRD) results indicated that the synthesized complex is a crystalline substance, and the scanning electron microscopy (SEM) analytic results showed that the synthesized complex is nanorod with an average size of about 40 nm. The thermogravimetry and differential thermal analysis (TG-DTA) result showed that the nanoscale complex has good stability below 449 degrees C. Photoluminescence spectra (PL) spectra showed that the nanoscale complex emitted characteristic red luminescence of Eu (III) under ultraviolet light. PMID- 20358900 TI - Pre-heating effect on the catalytic growth of partially filled carbon nanotubes by chemical vapor deposition. AB - The surface reconstruction of the Fe catalyst films due to high temperature processing in hydrogen prior to nanotube nucleation and its effect on the growth morphologies of partially filled carbon nanotubes (CNTs) synthesized using atmospheric pressure chemical vapor deposition (APCVD) of propane was investigated. Results show that pre-heating of the catalyst film deeply influences the particle size distribution, which governs the growth morphologies of the corresponding CNTs. The distribution of the catalyst particles over the Si substrate was analyzed before and after the heat treatment by atomic force microscopy (AFM) which reveals that heat treatment causes clusters of catalyst to coalesce and form macroscopic islands. The X-ray diffraction (XRD) pattern of the grown material indicates that they are graphitic in nature. Scanning electron microscopy (SEM) analysis suggested that the growth density strongly depends on the pre heat treatment of the Fe catalyst film. Multiwalled CNTs with partial catalyst filling were observed via high-resolution transmission electron microscopy (HRTEM) measurements. The degree of graphitization of the CNTs also depends on the pre heating as demonstrated by Raman analysis. A simple model for the growth of partially catalyst filled nanotubes is proposed. PMID- 20358901 TI - Copper pattern on self-assembled monolayer through microcontact printing. AB - Cu pattern on 3-mercaptopropyltrimethoxysilane self-assembled monolayers (MPTS SAMs) modified glass substrate was achieved by a combination of hydrophobic treatment through microcontact printing, activation and electroless plating. The MPTS-SAMs modified glass substrate was selectively deactivated by microcontact printing 1-hexadecanethiol ethanol solution. X-ray photoelectron spectroscopy (XPS) and water contact angle measurements confirmed that a selectively deactivated pattern was obtained, which was attributed to the formation of disulfide linkages between MPTS and 1-hexadecanethiol. The substrate was selectively activated by dipping into Ag colloids solution and then applied for electroless Cu plating. XPS spectra suggested an ideal catalytic pattern on the substrate due to the deposition of Ag particles on the MPTS and the formation of S-Ag bonds. SEM showed that the microstructure of Cu pattern on MPTS-SAMs was in good agreement with the corresponding silicon master with a resolution of 10 microm. The average electrical resistivity was about 1.8 x 10(-6) omegacm, measured by four-point probe technique. The results suggested that microcontact printing deactivating reagents on SAMs is a potential technique for Cu patterns preparation. PMID- 20358902 TI - Crystallization of a (1-butene)-ethylene copolymer in phase I directly from the melt in nanocomposites with montmorillonite. AB - Nanocomposites based on a copolymer of 1-butene and ethylene filled with montmorillonite (Cloisite 15A) were studied, obtaining for the first time crystallization from the melt directly into phase I. The polymorphism of the polymer and the dispersion of the filler in the matrix were investigated. The effect of the compatibilizer (PB-g-MA) on these properties was also singled out. The dramatic increase in the rate of the II --> I phase transition due to montmorillonite was attributed to the alteration in the phase stability diagram of the matrix, due to the introduction of defects and to induction of local pressure on the crystalline domains. PMID- 20358903 TI - Self-assembly of biological membranes into 200-400 nm aqueous compartments. AB - Membrane formation by amphipathic mixtures in aqueous environments is central to eukaryotic biology. Formation of aqueous compartments enclosed by membranes is of immense importance in designing liposomal systems for pharmaceutical applications. It is also continuously controlled within the dynamic environment of a living cell and, during cell division. In spite of over four decades of research on protein-free lipid bilayers, membrane compartment formation is still an art rather than science. This is because the experimental efforts to date have been aimed at making aqueous compartments from different lipid mixtures in different buffers and solutions of different ionic strengths. Thus, even similar methodologies produce varying results in different laboratories. In this work, we provide for the first time, experimental parameters of minimum hydration volume and maximum possible volumes for aqueous entrapments formed by DOPE:DOPC:Chol stoichiometries similar to intracellular environments and those used in pharmaceutical research for liposomal systems. We define a new experimental parameter of "Critical Compartmentalization Concentration" for formation of membrane-bound 200-400 nm aqueous compartments by these amphipathic mixtures in the simplest possible controlled environment of pure water. We report the first experimental insights into "equations" governing self-assembly leading to formation of membrane compartments encapsulating aqueous volumes. Our work opens a completely new avenue for engineering of aqueous compartment and liposomal preparations using known biological lipids in different aqueous environments. PMID- 20358904 TI - Nanocapsules prepared from amorphous polyesters: effect on the physicochemical characteristics, drug release, and photostability. AB - The influence of the polymeric amorphous materials on the physicochemical and drug release properties of drug-loaded nanocapsules as well as their role on the protection of the entrapped drug against the degradation induced by UV radiation was evaluated. Nanocapsules were prepared by interfacial deposition of preformed polymer (PLA, PLGA 50:50, and PLGA 85:15) using clobetasol propionate as the drug model. In vitro drug release was evaluated by the dialysis bag method. Photochemical stability was studied under UVA radiation. After preparation, all formulations presented nanometric mean size (180-200 nm), polydispersity index below 0.20, acid pH, negative zeta potential, and encapsulation efficiency close to 100%. Clobetasol propionate-loaded PLGA nanocapsules presented a lower physicochemical stability, showing a high drug leakage during 3 months of storage. In vitro studies showed biphasic drug release from all nanocapsules (according to an anomalous transport) and no influence of the hydrophilic characteristics of the amorphous polymeric material on the release rate. The photostability of clobetasol propionate under UVA radiation was improved by its incorporation into PLA and PLGA nanocapsules showing that besides semicrystalline polymers, amorphous polymers could also efficiently protect nanoencapsulated drugs against UV radiation. PMID- 20358906 TI - A new two-step route to CdTe micrometer-scaled spindles and nanorods. AB - In this study, a simple and convenient synthetic approach for producing high quality CdTe crystals has been developed. Cadmium telluride micrometer- and nanometer-scaled crystals were synthesized through a novel two-step route: CdTe nanoparticles were synthesized first via hydrothermal method and followed by diethylenetriamine (DETA) treatment. Scanning electron microscopy and transmission electron microscopy images showed that spindle- and rod-like CdTe crystals were obtained by varying the temperature of the hydrothermal reaction and the time of the DETA treatment. The possible growth mechanism is discussed. The advantages of this synthetic route, when compared to others, are under mild conditions that the reaction carried out and without any prerequisite on the particles in the second step. PMID- 20358905 TI - Nanoparticle platform to modulate reaction mechanism of phenothiazine photosensitizers. AB - Herein, we report on the synthesis of photosensitizing nanoparticles in which the generation of different oxidizing species, i.e., singlet oxygen (1O2) or radicals, was modulated. Sol gel and surface chemistry were used to obtain nanoparticles with specific ratios of dimer to monomer species of phenothiazine photosensitizers (PSs). Due to competition between the reactions involving electron transfer within dimer species and energy transfer from monomer triplets to oxygen, the efficiency of 1O2 generation could be controlled. Nanoparticles with an excess of dimer have an 1O2 generation efficiency (S(delta)) of 0.01 while those without dimer have a S(delta) value of 0.4. Furthermore, we demonstrate that the PS properties of the nanoparticles are not subjected to interference from the external medium as is commonly the case for free PSs, i.e., PS ground and triplet states are not reduced by NADH and ascorbate, respectively, and singlet excited states are less suppressed by bromide. The modulated 1O2 generation and the PS protection from external interferences make this nanoparticle platform a promising tool to aid in performing mechanistic studies in biological systems. Also, it offers potential application in technological areas in which photo-induced processes take place. PMID- 20358907 TI - Pulse laser deposited nanocrystalline cobalt ferrite thin films. AB - Cobalt ferrite thin films were pulsed laser deposited on fused quartz substrates at different substrate temperatures and ex-situ annealed at 750 degrees C in air. Grain size of these films was found to be 6-44 nm. Magnetization of these nanocrystalline thin films was found to be dependent on the substrate temperature. Magnetization higher than the cobalt ferrite bulk value was observed in the room temperature deposited film after post deposition annealing at 750 degrees C. This could be explained on the basis of a changed cation distribution in the film caused by quenching during deposition. PMID- 20358908 TI - Surface plasmon resonance tuning of silver nanoparticle array produced by nanosphere lithography through ion etching and thermal annealing. AB - It was demonstrated that size of the Ag nanoparticles array fabricated by nanosphere lithography (NSL) can be changed as needed by reactive ion etching (RIE) of the self-assembled polystyrene (PS) nanosphere template and post annealing of the Ag particle array. A macroscopic 2D array of ordered Ag nanoparticles stretching over an area greater than 1 cm2 was achieved using a modified nanosphere lithography method. The wavelength corresponding to the extinction maximum of the surface plasmon resonance (SPR) from the Ag nanoparticle array was systematically tuned by RIE of the PS template. Additional tuning of SPR was achieved by post-annealing the Ag nanoparticles which induced shape-changes in the Ag nanoparticles. We demonstrated that SPR can be tuned over the entire visible spectrum by RIE of the PS mask and thermal annealing, which can be potentially used to display localized SPR spectrum (hence, different color) throughout the visible range. PMID- 20358909 TI - Facile and controllable growth of ZnO 1D nanostructure arrays on Zn substrate by hydrothermal process. AB - ZnO nanorod, nanowire and nanotube arrays have been synthesized respectively on Zn substrates using a simple hydrothermal method. The morphology, size, length, density and uniformity of ZnO nanostructures can be well controlled by changing the different reaction conditions. The effects of substrates, temperature, positive and negative ions on the growth of nanostructure have been studied in detail. The results indicate that the addition of MgCl2 facilitates the growth of ZnO nanowires with higher density and formation of well-aligned nanowire arrays. The use of ammonia induces growth of longer nanowires but with lower density. PL spectrum show only strong UV emission at 385 nm, and no green band emission was observed, suggesting the excellent crystal quality of the nanowires. PMID- 20358910 TI - One-step route to wurtzite-structured ZnS thin nanorods in pure ethylenediamine or mixed solvent. AB - In the paper, we report one-step synthesis of novel wurtzite-structured ZnS three dimensional architectures assembled from thin nanorods in mixed solvent of ethylenediamine (en) and ethylene glycol, and wurtzite ZnS nanorods in a pure en solvent, both adopting Zn(CH3COO)2 x 2H2O and (NH2)2CS as raw materials. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high resolution transmission electron microscopy and selected area electron diffraction were applied to characterize the samples. It was found that the volume ratio of solvents and the concentration of (NH2)2CS played important roles in the formation of wurtzite-structured ZnS nanorods, and the thin wurtzite ZnS nanorods with mean diameter of 6 nm were successfully synthesized. The optical absorption edges of the thin ZnS nanorods were found to be blue-shifted compared with that of the bulk ZnS due to the quantum confinement effect. PMID- 20358911 TI - Preparation, structure and catalytic activity of Pt-Pd bimetallic nanoparticles on multi-walled carbon nanotubes. AB - Different amounts of Pd, Pt and Pt-Pd alloy nanoparitcles were deposited on mesoporous carbon nanotube microparticles through an easy polyol reduction method. Pt-Pd bimetallic nanoparticles of varied Pt/Pd molar ratios have alloy structures that are identified by XRD, TEM with EDX and XPS. The activities of five different nanocatalysts were evaluated for the hydrogenation of allyl alcohol, and the alloy nanocatalyst showed superior activity at high Pd loading. More importantly, the synthesized nanocatalysts could be easily recovered completely from the final reaction solution via conventional filtration. PMID- 20358912 TI - On the application of different bimetallic alloy nanoparticle combinations in fiber optic surface plasmon resonance salinity sensor and its performance optimization against thermal effects. AB - In the present work, we have theoretically investigated the capability of the layer composed of various combinations of bimetallic alloy nanoparticles to be used in fiber optic salinity sensor based on the technique of surface plasmon resonance (SPR). The metals considered for the present analysis are silver, gold, copper, and aluminum. The performance of the sensor with six different bimetallic alloy nanoparticle combinations is evaluated and compared. Furthermore, the performance optimization is carried out in order to minimize the effect of the variation in operating temperature. The overall performance is analyzed in terms of four parameters: sensitivity, signal-to-noise ratio, detection limit, and operating range for the salinity detection in the water sample. On the basis of the comparisons and logistic criteria, the best possible bimetallic alloy combinations along with requisite alloy composition ratio are predicted. The nanoparticle layer made of bimetallic alloy is capable of simultaneously providing larger values of sensitivity, signal-to-noise ratio, detection and operating range, against the temperature-variation compared to single metallic nanoparticle layer. PMID- 20358913 TI - Structural investigations of hybrid TiO2/CNTs nanomaterials. AB - In the present study, pure TiO2 and hybrid TiO2/CNTs nanomaterials are prepared by sol gel technique. Post heat treatment is performed at 600, 800, and 1000 degrees C, respectively. The structural characterizations are performed by field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction and synchrotron X-ray absorption spectroscopy techniques. Experimental results show that anatase to rutile transformation can be observed for pure TiO2 nanomaterials after heat treatment at 800 degrees C. The anatase to rutile transformation is inhibited by carbon nanotubes, and therefore only anatase phases for TiO2 nanomaterials can be observed in the hybrid nanomaterials. The 600 degrees C hybrid nanomaterials show a microstructure with CNTs covered by continuous TiO2 films of numerous small nanoparticles. After applying heat treatment on the hybrid nanomaterials at 1000 degrees C, only TiO2 nanoparticles adhere individually to the uncovered CNTs. Though all hybrid nanomaterials exhibit anatase TiO2, synchrotron X-ray absorption spectra investigations reveal that hybrid TiO2/CNTs exhibit different electronic properties as compared to those of pure TiO2 nanomaterials. PMID- 20358914 TI - Size effect of nano scale phase change random access memory. AB - In this paper, we have investigated the size effect of nano scale PRAM using three-dimensional finite element analysis tool. The reset current and temperature profile of PRAM cells with top and bottom electrode contact hole size were calculated by the numerical method. And temperature profile of PRAM unit cell with size and thickness of GST thin film was simulated. As top electrode contact size was smaller, reset current decreased. But these variations couldn't affect to operate memory. On the other hand, as bottom electrode contact size was smaller, reset current abruptly decreased. PMID- 20358915 TI - Efficient transfer of reporter gene-loaded nanoparticles to bone marrow stromal cells (D1) by reverse transfection. AB - Nucleic acids can be complexed with cationic polymer to form DNA nanoparticles (polyplex) which are then immobilized on the surface coated extracellular matrix protein (ECM), the process termed as reverse transfection. ECM-containing proteins provide a surface for cell attachment and sustain the release of polyplexes from their surface, thereby inducing transgene expression for prolonged period of time. Consequently, long-term expression of the desired protein can be achieved with the smaller amount of required DNA, as compared to bolus delivery. First of all, we investigated the different ECM components as a coating material and the range of optimal coating density in different ECM was examined for enhanced transfection to neighboring cells. Reporter genes such as luciferase (luc) and enhanced green fluorescent protein (eGFP) were initially used to quantitate transfection efficiencies from polyplex from the coated ECMs of Collagen type I (Col I), fetal bovine serum protein (FBS), bovine serum albumin (BSA). DNA was complexed with positively charged polyethyleneimine (PEI) at N/P ratio 9. Our initial work exhibited that, in the case of both NIH/3T3 cell line and bone marrow stromal (D1) cell line, Col I facilitated the greatest cell adhesion compared to the other coating proteins and 0.5 microg/cm2 of Col I coating density resulted in highest transfection efficiency. On the other hand, comparison of reverse delivery system with atelocollagen-I have shown that reverse delivery system to yield ten times higher transfection efficiency than atelocollagen-PEI/DNA delivery system and one hundred times higher than atelocollagen-naked plasmid delivery system. Moreover, the amount of DNA used for reverse delivery system was much lower than the other systems. This methodology would be applied to induce cellular differentiation in 3-dimensional scaffold after coating scaffolds with genes inducing the differentiation in the nanoparticle formulation. Our final goal is to search for the optimal conditions for the differentiation of stem cells to specific cell types. PMID- 20358916 TI - Autothermal reforming of propane over Ni-based hydrotalcite catalysts. AB - Ni-based hydrotalcite catalysts were investigated for ATR of propane in a fixed bed flow reactor. The reactions were carried out with a H2O/C/O2 stream ratio of 3/1/0.73 at temperatures ranging from 300 to 700 degrees C. The solvents used in the manufacture of Ni-based catalysts noble metal/Ni/MgAl catalysts or substituted active material were changed in order to decrease the level of catalyst deactivation. The use of a mixture of ethanol and water during the formation of the Pd-Ni/MgAl catalyst produced a higher hydrogen yield than that using water only. In addition, the use of acetone in the synthesis of Ru-Ni/MgAl catalyst produced a higher hydrogen yield than using water only. This shows that the solvents used for the noble metals affect the degree of dispersion and particle size of the nickel and prevented carbon deposition resulting in the enhanced hydrogen selectivity and catalyst activity. Active metals were substituted during the preparation of hydrotalcite catalysts. Among the catalysts prepared with various ratio (Ni:Fe) tested at high temperature, the ratio, Ni:Fe = 75:25, showed best performance. There was less sintering of Ni particles due to substitution of the active metal at the optimal ratio. PMID- 20358917 TI - Fabrication of highly uniform conductive polypyrrole nanowires with DNA template. AB - Deoxyribonucleic acid (DNA) is considered as one of the alternative materials for electronic device applications; however, DNA has critical limitation to electronic device applications due to its low electrical conductivity and unreliability. Therefore, it is required for electronic devices to prepare the well defined conductive polymer nanowires with DNA as a template. Polypyrrole (PPy) is an attractive polymer due to its high conductivity and environmental stability in bulk; although it is well known that ammonium persulfate (APS) used for the polymerization of pyrrole causes the deformation of DNA molecules. We minimized the damage of immobilized DNA strands on (3-aminopropyl) triethoxysilane (APTES) modified silicon wafer during APS polymerization. Atomic force microscopy (AFM) images from different APS treatment times and from using the vortex process obviously showed the effect on the synthesis of individual and continuous polypyrrole nanowires (PPy NWs). The PPy NWs at various pyrrole concentrations had similar height; however, the higher concentration gave more residues. Fourier transform-infrared spectroscopy (FT-IR) spectroscopy provided the strong evidence that PPy NWs were successfully synthesized on the DNA strands. PMID- 20358918 TI - Maskless laser direct patterning of PEDOT/PSS layer for soluble process organic thin film transistor. AB - In this work, we have fabricated TIPS-pentacene TFTs with conductive polymer (3,4 ethylenedioxythiophene):poly(4-stylenesulfonate) (PEDOT:PSS) source/drain electrodes which is patterned by maskless laser direct patterning (LDP). The 5 microm resolution of source and drain patterns with PEDOT:PSS were clearly defined. Furthermore, the OTFTs with 10-microm channel length were successfully achieved by exposing the focused Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser beam onto the spin-coated PEDOT:PSS films and developing with deionized water. The electrical performance of the TIPS-pentacene TFTs with PEDOT:PSS source/drain electrodes were improved with decrease of the sheet resistance of PEDOT:PSS films when the PEDOT:PSS films were annealed at the temperature above 200 degrees C. PMID- 20358919 TI - Low power consumption and high sensitivity carbon monoxide gas sensor using indium oxide nanowire. AB - In this paper, micro gas sensor was fabricated using indium oxide nanowire for effective gas detection and monitoring system. Indium oxide nanowire was grown using thermal CVD, and their structural properties were examined by the SEM, XRD and TEM. The electric properties for microdropped indium oxide nanowire device were measured, and gas response characteristics were examined for CO gas. Sensors showed high sensitivity and stability for CO gas. And with below 20 mw power consumption, 5 ppm CO could be detected. PMID- 20358920 TI - Fluorenylpyridine-derived iridium complexes for electrophosphorescent light emitting diodes. AB - To develop efficient emitting materials for organic light-emitting diodes (OLEDs), a series of cyclometalated iridium complexes with 2-fluorenylpyridine derived ligands were synthesized. Complexes 1-4 exhibited yellow to red phosphorescence with quantum yields of 0.17-0.33 in degassed CH2Cl2. Multilayered OLEDs were fabricated by using these iridium complexes as dopant materials. In the device employing complex 1 as a dopant, the maximum luminance, maximum luminance efficiency and maximum power efficiency were 15600 cd/m2 at 14 V, 12.8 cd/A, and 8.94 Im/W, respectively, at the CIE coordinates of (0.648, 0.350), which is close to the saturated red emission. The electron-withdrawing carbonyl substituent groups affected markedly the EL performances of fluorenylpyridine derived iridium complexes as red emitting materials. PMID- 20358921 TI - Organic thin film transistor with poly(4-vinylbiphenyl) blended 6,13 bis(triisopropylsilylethynyl)pentacene on propyleneglycolmonomethyletheracetate dielectric surface. AB - This paper presents the latest results in the use of soluble materials, such as organic semiconductors (OSCs) and gate-dielectrics, for simplified processing of organic thin film transistors (OTFTs). In this work, the fabrication of a solution-processed OTFT, with 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene) and TIPS-pentacene mixed with poly(4-vinylbiphenyl) (PVBP) as the OSC, and propyleneglycolmonomethyletheracetate (PGMEA) as the gate-dielectric, is described. From electrical measurements, we observed exemplary I-V characteristics for these TFTs. Device performance characteristics have been obtained, including the charge carrier mobility (micro) of 1.47 x 10(-2) cm2Ns, threshold voltage (V(T)) of -11.36 V, current on/off ratio (I(ON/OFF)) of 1.08 x 10(4), sub-threshold swing (SS) of 2.13 V/decade for an OTFT with PVBP blended TIPS-pentacene and micro of 1.39 x 10(-4) cm2/Vs, V(T) of 0.7 V, I(ON/OFF) of 1.64 x 10(3), SS of 4.21 V/decade for an OTFT without polymer binder, individually. PMID- 20358922 TI - Sulfonated poly(styrene-b-ethylene-co-butylene-b-styrene) and fullerene composites for ionic polymer actuators. AB - Ionic polymer-metal composite (IPMC) actuators employing sulfonated poly(styrene b-ethylene-co-butylene-b-styrene) (SSEBS) ionomer and fullerene-C60 composite membrane were developed. Due to the poor electroactive performance of IPMC actuators employing pure SSEBS, fullerenes as the reinforcement agent are incorporated. The bending responses under both direct current (DC) and alternating current (AC) excitations were investigated. Compared with the actuator based on pure SSEBS, the tip displacement of IPMC actuator based on Fullerene-SSEBS composites has great improvement under DC excitations, and also the responses are quick and harmonic under AC excitations. More meaningful improvement is that Fullerene-SSEBS based IPMC actuators don't have back relaxation towards the cathode under DC activation for a long time. SEM study was carried out on the samples of Fullerene-SSEBS actuators. Platinum layers were finely synthesized on the interfaces of Fullerene-SSEBS actuators. Present results show that the fullerene, C60, can be successfully applied to reinforce the electro-mechanical properties of the ionic polymer metal composite actuators. PMID- 20358923 TI - Functional microscopy tip fabrication by an electric conductive nanowire. AB - The functional microscopy tip was fabricated by an electric conductive nanowire (NW). Single crystalline nickel silicide (NiSi) NW grown by plasma-enhanced chemical vapor deposition has an excellent electrical conductivity. On behalf of the advantages in tiny size and conductivity of NiSi NW, it was utilized as a nanoscale probe. Dielectrophoretic method was applied to position the NW. The NiSi NW containing solution was dropped in an ac electric field applying system to align the NiSi NW on a Si cantilever. The fabricated NiSi NW-sitting functional microscopy tip obtained the information of topography and electrical signals from a nanoscale structure. It shows the high potential of nanoscale microscopy tip fabrication at reduced processing steps. PMID- 20358924 TI - Prediction of TiO2 thin film growth on the glass beads in a rotating plasma chemical vapor deposition reactor. AB - We calculated the concentration profiles of important chemical species for TiO2 thin film growth on the glass beads in the TTIP + O2 plasmas and compared the predicted growth rates of thin films with the experimental measurements. The film thickness profile depends on the concentration profile of TiO(OC3H7)3 precursors in the gas phase because TiO(OC3H7)3 is the main precursor of the thin film. The TTIP concentration decreases with time, while the TiO(OC3H7)3 concentration increases, and they reach the steady state about 2 approximately 3 sec. The growth rate of TiO2 film predicted in this study was 9.2 nm/min and is in good agreements with the experimental result of 10.5 nm/min under the same process conditions. This study suggests that a uniform TiO2 thin film on particles can be obtained by using a rotating cylindrical PCVD reactor. PMID- 20358925 TI - Effect of nanoparticle coating on the thermal conductivity of microporous thermal insulations. AB - Microporous thermal insulations were prepared from mixtures of nano-sized fumed silica, micron-sized fibers and opacifier particles. Those micron-sized particles were dry coated with nano-sized fumed silica particles by mechanical process using a compressive-shear type mill. The effect of nanoparticle coating on the thermal conductivity of the insulation media was investigated using a hot-wire method. Effect of nanoparticle coating was found to be more pronounced for the insulation composed of fumed silica and fiber than for the one composed of fumed silica, fiber and an opacifier. By adding 15% SiC or TiO2 opacifier, the thermal conductivity of the insulation samples could be lowered to 0.08 Wm(-1) K(-1) at temperature range of 805 approximately 817 degrees C. The temperature dependent thermal conductivity of the sample containing glass fiber did not exhibit any remarkable changes compared to the one containing ceramic fiber. PMID- 20358926 TI - Ferredoxin molecular thin film with intrinsic switching mechanism for biomemory application. AB - A biomemory device consisting of cysteine modified ferredoxin molecules which possess a memory effect via a charge transfer mechanism was developed. For achieving an efficient bioelectronic device, cysteine modified ferredoxin was developed by embodying cysteine residues in ferredoxin by site--directed mutagenesis method to directly coordinate with the gold (Au) surface without use of any additional linkers. The thin film formation of ferredoxin molecules on Au electrode is confirmed by surface plasmon resonance (SPR) spectroscopy and scanning tunneling microscope (STM). Cyclic voltammetry (CV) and open circuit potential amperometry (OCPA) methods were used to verify the memory switching characteristics of the fabricated device. The charge transfer between ferredoxin protein molecules and Au electrode enables a bi-stable electrical conductivity allowing the system to be used as a digital memory device. Data storage is achieved by applying redox voltages which are within the range of -500 mV. These results suggest that the proposed device has a function of memory and can be used for the construction of a nano-scale bioelectronic device. PMID- 20358927 TI - Effects of poloxamer 188 on the characteristics of poly(lactide-co-glycolide) nanoparticles. AB - We tested the effects of poloxamer 188 on the preparation and characteristics of poly(lactice-co-glycolide) (PLGA) nanoparticles containing all-trans retinoic acid (ATRA). Spherical nanoparticles incorporated ATRA were prepared by an emulsification-diffusion method increasing concentrations of poloxamer 188 decreased nanoparticle size. The endothermic peak of ATRA at 183 degrees C disappeared in the nanoparticles and X-ray diffraction measurements showed the disappearance of characteristics of ATRA suggesting the change of the crystallinity of ATRA in the nanoparticles to an amorphous state. ATRA release in vitro increased as the concentration of poloxamer increased. The mean residence time of ATRA-loaded nanoparticles after the administration of a single intravenous dose to rats was longer than that of the sodium ATRA solution. The anti-cancer activity of ATRA-loaded nanoparticles in the human leukemia-60 cell line was similar to free ATRA. Thus, PLGA/poloxamer nanoparticles can provide a sustained release preparation of ATRA. PMID- 20358928 TI - Ultra-sensitive detection of tumor necrosis factor-alpha on gold nano-patterned protein chip formed via E-beam nanolithography by total internal reflection fluorescence microscopy. AB - We detected "tumor necrosis factor-alpha (TNF-alpha)" on a gold nanoarray protein chip at the attomolar (aM) concentration level (x10(-18)) by total internal reflection fluorescence microscopy (TIRFM). The 4 x 5 nanoarray patterning of gold with a spot diameter of 500 nm was successfully achieved on 10-mm square glass substrates using an electron beam evaporator. The dithiobis(succinimidyl propionate) as a protein linker and the Protein A/G to help oriented immobilization of antibody were used. The interactions of individual protein molecules were detected based on the sandwich fluorescence immunoassay by TIRFM. The linear regression equation for TNF-alpha in the range of 13 aM-130 fM was determined to be y = 6687.8x +126133 (R = 0.9938). The detection limit was 1.3 aM (S/N = 3). These results show that TNF-alpha as a tumor marker protein molecule was applied to gold nano-patterned protein chip. PMID- 20358929 TI - Nano-sized silver patterning using nano-ink with an indirect patterning method of nanoimprint and lift-off processes. AB - Silver nanopatterns were fabricated using a nanoimprint and lift-off process using silver nano-ink. Particle-based silver nano-ink was used to fabricate metal patterns below 100 nm in a lift-off process without the undercut shape of polymer patterns typically required in a conventional lift-off process using evaporated metal. The silver film made by spin-coating the silver nano-ink and removing the solvent using PDMS, has a low density compared to evaporated metal film; hence, unnecessary nano-ink that is not part of the pattern area is easily eliminated during the lift-off process. Using the proposed patterning process, patterns defined on a stamp were successfully transferred to the nano-ink through nanoimprinted polymer patterns on a four-inch Si wafer. Compared to other metal patterning methods that involve lift-off processes, the proposed metal patterning process is a simple and cost-effective process capable of fabricating the micro- and nano-sized metal patterns due to its low operating temperature and one-step polymer patterning process by nanoimprinting. PMID- 20358930 TI - Design and optimization of in-plane actuator driven cantilever with high sensitivity sensors. AB - We present a new mode of actuation and excitation for cantilevers, which endows cantilevers with large deflection for the specific application. Differing from all of the conventional methods in which the deflection is aroused by the vertical drive of cantilever itself or external vibration, the bending and oscillating actuation here is by means of the in-plane actuators, where the out of-plane motion of the cantilever is driven by the actuation of integrated in plane actuators combined with curl-shaped cantilever. Because the driving force of the horizontal actuator can be converted through curl-shaped cantilever into a bending moment that results in cantilever deflection, out-of-plane actuation source for cantilever deflection is independent of the cantilever itself. An in plane electrostatic actuator with comb-drive structures that has two sets of fixed fingers and one set of moving fingers was introduced for both statically bending and dynamically oscillating the cantilever. The optimal structure was obtained through an analytical model and finite element simulation; it achieves a substantially greater deflection and a concentrated stress distribution located on the hinges, in which the integrated piezoresistive sensors are embedded to suffer from larger stress for high sensitive sensing. PMID- 20358931 TI - Nanoscale film formation of recombinant azurin variants with various cysteine residues on gold substrate for bioelectronic device. AB - Nanoscale film fabrication of recombinant azurin variants with various cysteine residues on gold substrate was developed without any surface modification for bioelectronic device. We have modified azurin with different number of cysteine residues at its amino acid chain based on site-directed mutagenesis. The resulting recombinant protein, azurin, retained its original redox property in the same manner as native azurin. Recombinant azurin was immobilized on Au substrate by strong affinity between thiol of cysteine and gold. The orientations of recombinant azurin with various cysteine residues immobilized on the Au substrate were analyzed by fluorescence microscope, scanning tunneling microscope, and surface plasmon resonance. Our data revealed that binding activity of recombinant azurin with three cysteine residues on the Au substrate significantly increased in comparison to single residue azurin. Immobilization method of highly oriented recombinant azurin based on cysteine-modification could be useful for the nanoscale film fabrication of nanobiochip. PMID- 20358932 TI - Enhanced biomolecular detection based on localized surface plasmon resonance (LSPR) using enzyme-precipitation reaction. AB - An enzyme-catalyzed precipitation reaction was employed as a means to increase the change in the LSPR signal after intermolecular bindings between antigens and antibodies occurred on gold nanodot surfaces. The gold nanodot array with an diameter of 175 nm and a thickness of 20 nm was fabricated on a glass wafer using thermal nanoimprint lithography. The human interleukin (hIL) 5 antibody was immobilized on the gold nanodot, followed by binding of hIL 5 to the anti-hIL 5. Subsequently, a biotinylated anti-hIL 5 and a alkaline phosphatase conjugated with streptavidin were simultaneously introduced. A mixture of 5-bromo-4-chloro-3 indolyl phosphate p-toluidine (BCIP) and nitro blue tetrazolium (NBT) was then used for precipitation, which resulted from the biocatalytic reaction of the alkaline phosphatase on gold nanodot. The LSPR spectra were obtained after each binding process. Using this analysis, the enzyme-catalyzed precipitation reaction on gold nanodots was found to be effective in amplifying the change in the peak wavelength of LSPR after molecular bindings. PMID- 20358933 TI - Electroluminescence property of highly soluble Ir(III) complex utilized by various hole blocking layers in polymer light emitting diodes. AB - The tris(2-phenylpyridine)iridium(III) [Ir(ppy)3] is a well known highly efficient green light-emitting phosphorescent guest dye dopant, but its relatively low solubility has been obstructing it to be used in polymer light emitting diodes (PLEDs). According to our latest reports the solubility of Ir(ppy)3 complexes with the carbazole ligands, i.e., Ir(Czppy)3, was improved significantly in organic solvents, and was sufficient to be used in soluble process. This highly soluble Ir(Czppy)3 complex showed remarkably higher photoluminescence characteristics than conventional Ir(ppy)3, but it showed similar or comparably better electroluminescence (EL) characteristics, when the PLED was composed by widely used conventional hole blocking layer (HBL) and electron transport layer; 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline and tris(8-hydroxyquinoline)aluminum, respectively. In this report, we applied various HBLs to improve the EL characteristics of soluble Ir(III) complex based phosphorescent PLEDs. The PLEDs utilized by the wide band-gap 3-(4-biphenylyl)-4 phenyl-5-tert-butylphenyl-1,2,4-triazole demonstrated highly improved the current and the external quantum efficiency of 17.61 cd/A and 6.42%, respectively. PMID- 20358934 TI - Interfacial reactions of nano-structured Cu-doped indium oxide/indium tin oxide ohmic contacts to p-GaN. AB - Interfacial microstructure and elemental diffusion of Cu-doped indium oxide (CIO)/indium tin oxide (ITO) ohmic contacts to p-type GaN for light-emitting diodes (LEDs) were investigated using cross-sectional transmission electron microscopy (XTEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction. The CIO/ITO contacts gave specific contact resistances of approximately 10(-4) omegacm2 and transmittance greater than 95% at a wavelength of 405 nm when annealed at 630 degrees C for 1 min in air. After annealing at 630 degrees C, multi-component oxides composed of Ga2O3-In2O3, Ga2O3-CuO, and In2O3-CuO formed at the interface between p-GaN and ITO. Formation of multi-component oxides reduced the barrier height between p-GaN and ITO due to their higher work functions than that of ITO, and caused Ga in the GaN to diffuse into the CIO/ITO layer, followed by generation of acceptor-like Ga vacancies near the GaN surface, which lowered contact resistivity of the CIO/ITO contacts to p-GaN after the annealing. PMID- 20358935 TI - Preparation of TiO2 nanoparticle from Ti-salt flocculated sludge with dye wastewater. AB - Dye wastewater flocculation using TiCl4 and FeSO4 coagulants was studied for organic removal and precipitation efficiency. Moreover, TiCl4 was assessed in a pilot-scale flocculation process to investigate organic removal and solution pH effect. A large amount of TiO2 was produced from sludge of Ti-salt flocculation in dye wastewater. This flocculation process simultaneously reduces a large amount of sludge produced from wastewater. The TiO2 nanoparticle was characterized in terms of physical and chemical properties. Results showed that 77.6% of organic matter was removed from dye wastewater when using FeSO4 as coagulant, while TiCl4 degraded 75.9% of organic matter. On the other hand, floc precipitation efficiency was better for TiCl4 if compared with FeSO4. The optimum concentration of TiCl4 for pilot-scale flocculation was found to be equal to 2.1 g/L. DWT (Dye wastewater titania) size was 15-20 nm, mainly doped with carbon atoms and exhibited a dominant anatase structure. DWT was similar to P-25 in decomposing acetaldehyde under UV-irradiation and complete photocatalytic degradation was achieved after 140 min. PMID- 20358936 TI - Chemical sensor based on porous silicon dual transducers. AB - Novel porous Si exhibiting dual optical properties, both Fabry-Perot fringe (optical reflectivity) and photoluminescence, were developed and used as chemical sensors. Porous Si samples were prepared by an electrochemical etch of p-type silicon under the illumination with a 300 W tungsten filament bulb for the duration of etch. The surface of porous Si was characterized by FT-IR instrument. The porosity of samples was about 80%. Both reflectivity and photoluminescence were simultaneously measured under the exposure of organic vapors. The shift of Fabry-Perot fringe to the longer wavelength under the exposure of chloroform vapors was obtained. The steady-state photoluminescence spectra and quenching photoluminescence under the exposure of various organic vapors were obtained. A set of organic compounds were analyzed by both quenching photoluminescence and change of optical thickness. PMID- 20358937 TI - Multiwalled carbon nanotube/polyarcylonitrile composite as anode material for microbial fuel cells application. AB - A microbial fuel cell (MFC) is an electrochemical device that can directly convert the chemical energy stored in organic matter into electricity using microorganisms as a biocatalyst. The performance of multiwalled carbon nanotube (MWCNT)/polyarcylonitrile (PAN) composite modified carbon paper electrodes in two chambered MFC was investigated. The electrocatalytic behaviors of the MWCNT/PAN composite anode were examined by using cyclic voltammetry. The MWCNT/PAN composite anode showed better electrochemical performance than that of PAN anode without MWCNT and the electricity generation of the MFC increased along with the increase of the MWCNT composite loading. The 5 wt% MWCNT/PAN composite anode has the highest electrochemical activity and its maximum power density is found to be 45 mW/m2 with acetate. PMID- 20358938 TI - A new PEG-lipid conjugate micelle for encapsulation of CdSe/ZnS quantum dots. AB - A new polymer conjugate of poly(ethylene glycol) (PEG) and 10,12-pentacosadiynoic acid (PCDA), PEG-PCDA conjugate, was synthesized by coupling reaction between carboxyl group of PCDA and hydroxyl group of PEG. Luminescent CdSe/ZnS QDs were encapsulated in the polymer micelles of mixtures of PEG-PCDA and PCDA using solid dispersion method to prepare water-soluble and biocompatible QD micelles. Upon UV irradiation, the core of QD micelles was further stabilized by intramicellar crosslinking between neighboring PCDA moieties. The polymer conjugate was characterized by 1H-NMR, FT-IR, and GPC measurements, and thereof QD micelles observed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The QD micelles were spherical with diameters in the range of 30-190 nm. The encapsulated QDs in polymer micelles are water-soluble and have the high potential for applications in biomedical imaging and detection due to their good colloidal stability and biocompatible surface. PMID- 20358939 TI - Intratumoral administration of anti-KITENIN shRNA-loaded PEI-alt-PEG nanoparticles suppressed colon carcinoma established subcutaneously in mice. AB - Biodegradable gene carrier, termed as PEI-alt-PEG, has been synthesized based on Michael addition reaction between lower Mw PEI and poly(ethylene glycol) (PEG) diacrylate and tested its potential of anti-metastatic cancer gene therapy by using anti-KITENIN short hairpin RNA. KITENIN is known to promote invasion of mouse colon adenocarcinoma in vivo. Intratumoral administration of anti-KITENIN shRNA-loaded PEI-alt-PEG nanoparticles has shown suppressed proliferlation and enhanced apoptosis signal in tumor compared to commercial available liposome, leading to delayed tumor growth. PMID- 20358940 TI - Nanoemulsion-eicosapentaenoic acid enhanced alkaline phosphatase, calcium contents, and surface molecules expression during osteogenesis using mouse multipotent bone marrow stromal cells. AB - Long-chain eicosapentaenoic acid (EPA) is found mainly in marine oils, and has wide ranging biological effects. In this study, we evaluated the effect of nanoemulsion-EPA on the osteogenic differentiation of mouse mesenchymal stem cells (D1 cells). D1 cells were cultured in osteogenic differentiation medium (ODM) for 6 days and treated with nanoemulsion-EPA for 2 days and then subjected to various tests; MTT assays, alizarin red S staining, alkaline phosphatase (ALP) activity determinations, calcium contents analysis, reverse transcriptase polymerase chain reaction (RT-PCR), confocal microscopy, and flow cytometric analysis. D1 cells were found to differentiate into osteoblasts in the presence of osteogenic differentiation medium, as determined by positive alizarin red S staining, increased alkaline phosphatase activity and calcium contents, osteocalcin, osteopontin and Runx2 mRNA expressions, and by positive immunofluorescence staining against CD44 or CD51. Furthermore, osteogenic differentiation was enhanced when cells were treated with nanoemulsion-EPA, as determined by alizarin red S staining, elevated ALP activity, calcium contents and osteocalcin and Runx2 mRNA expression, and immunofluorescence staining and flow cytometric analysis for CD44. Furthermore, pretreatment with p38 inhibitor prior to nanoemulsion-EPA decreased alizarin red S staining and ALP activity. These findings suggest that nanoemulsion-EPA enhances osteogenic differentiation via the p38 pathway when administered to mouse mesenchymal stem cells in osteogenic differentiation medium. PMID- 20358941 TI - Highly efficient blue fluorescent materials based on fluorene derivatives end capped with arylaminofluorenylethylenes for organic light-emitting diodes. AB - Multilayered organic light-emitting diodes (OLEDs) were fabricated by using the new fluorine derivatives end-capped with arylaminofluorenylethylenes as dopant materials. The device structure was ITO/NPB/15% blue dopants doped in MADN/Bphen/Liq/Al. Among those, a device shows the maximum luminance of 40800 cd/m2 at 12 V, the luminous efficiency of 12.8 cd/A at 20 mA/cm2, power efficiency of 9.13 Im/W at 20 mA/cm2 and CIE(x,y) coordinates of (x = 0.188, y = 0.372) at 8 V. PMID- 20358942 TI - Folate conjugated poly(ester amine) for lung cancer therapy. AB - Folate conjugated poly(ester amine) (PEA) was prepared by reaction of folic acid with PEAs based on polycaprolactone (PCL) and low molecular weight polyethylenimine (LMW-PEI) with PEG as a linker. This novel gene carrier showed excellent physicochemical properties and relatively low cytotoxicity compared with PEI 25K. It showed excellent transfection efficiency through folate receptor mediated endocytosis. PMID- 20358943 TI - Optimum condition of anisotropic plasma etching for improving bending properties of ionic polymer-metal composites. AB - We presented an anisotropic plasma etching technique by reactive ion etcher (RIE) as a new pretreatment method of fabrication of ionic polymer-metal composite (IPMC). We already found that the new technique provided large displacement to the fabricated IPMC in the presence of low applied voltage. However, we did not examine the optimum condition for the anisotropic plasma etching. In this research, we tried to figure out optimum treatment condition of film in etcher. Nafion (by DuPont) films were etched using various etching time and shadow masks with various slit and space sizes. The etched samples were plated with Pt at top and bottom side by Oguro's reduction method. The surface morphology of fabricated IPMCs was characterized by SEM. And, we've measured surface resistance, bending displacement, and driving force in order to check the IPMC properties out. Here, we found that optimum condition for pre-treatment of Nafion was 1 min for etching time under shadow mask with 200 microm slit and 100 microm space. PMID- 20358944 TI - Temperature dependent electrical properties of organic light-emitting diodes using a Zn complex. AB - We synthesized a new electroluminescent material [(1,10-phenanthroline)(8 hydroxyqu inoline)] Zn(phen)q. The temperature dependence of the electrical properties of OLED using Zn(phen)q are studied to understand the electrical conduction mechanism. The current density-voltage characteristics are measured in the temperature range of 60 approximately 240 K and analyzed using a hopping model with an exponential trap distribution. At temperatures above 150 K, hopping conduction with an exponential trap distribution is dominant. We have obtained a characteristic trap depth of E(t) = 0.13 eV. PMID- 20358945 TI - Analysis of a metallic nano-rod polarizer using finite-difference-time-domain method. AB - The polarization behavior of metallic nano-rods has been analyzed by means of the finite-difference-time-domain method. When the average spacing between the nano rods is less than a half wavelength, the layer reflects the light polarized parallel to the nano-rods, as in a nano-slit. However, when the spacing is larger than a half wavelength, the metallic surface absorbs the light, polarized perpendicular to the rods, leading to a polarization switching. Multiple layers of nano-rods can make a polarizer with a high extinction ratio and good transmittance. PMID- 20358946 TI - Design and modeling of an efficiency horizontal thermal micro-actuator with integrated piezoresistors for precise control. AB - An integrated system made up of a double-hot arm electro-thermal microactuator and a piezoresistor embedded at the base of the 'cold arm' is proposed. The electro-thermo-mechanical modeling and optimization is developed to elaborate the operation mechanism of the hybrid system through numerical simulations. For given materials, the geometry design mostly influences the performance of the sensor and actuator, which can be considered separately. That is because thermal expansion induced heating energy has less influence on the base area of the 'cold arm,' where is the maximum stress. The piezoresistor is positioned here for large sensitivity to monitor the in-plane movement of the system and characterize the actuator response precisely in real time. Force method is used to analyze the thermal induced mechanical expansion in the redundant structure. On the other hand, the integrated actuating mechanism is designed for high speed imaging. Based on the simulation results, the actuator operates at levels below 5 mA appearing to be very reliable, and the stress sensitivity is about 40 MPa per micron. PMID- 20358947 TI - Explicit continuous current-voltage (I-V) models for fully-depleted surrounding gate MOSFETs (SGMOSFETs) with a finite doping body. AB - An analytical and continuous dc model for cylindrical doped surrounding-gate MOSFETs (SGMOSFETs) in the fully-depleted regime is presented. Starting from Poisson's equation, an implicit charge equation is derived approximately by a superposition principle with the exact channel potential and the charge equations in the depletion approximation. Also, a new explicit charge equation is derived from the implicit charge equation. The current equations without any charge-sheet approximation are based on the implicit and explicit charge control models, and both of them are valid for all the operation regions (linear, saturation, and subthreshold) and traces the transition between them without any fitting parameters. In the case of the SGMOSFETs with the fully-depleted condition, both of results simulated from the SGMOSFET models reproduce various 3D simulation results within 5% errors. PMID- 20358948 TI - Preparation of born-doped a-SiC:H thin films by ICP-CVD method and to the application of large-area heterojunction solar cells. AB - Hydrogenated amorphous silicon carbide (a-SiC:H) film has been widely used as an emitter p layer in solar cells. For the better p layer, wide optical bandgap, and high electrical conductivity should be obtained from the effective method. We prepared the boron-doped a-SiC:H thin films using inductively coupled plasma chemical vapor deposition (ICP-CVD) method and characteristics on the small-area (2 cm x 2 cm) as well as the large-area films (diameter of 100 mm) were shown on it. As a substrate, the n-type (100) oriented CZ c-Si (5.5 approximately 6.5 omega x cm, 650 microm) wafers were used and cleaned by using the reduced RCA method. A silane (SiH4) of 99.999% purity, H2 and 60% hydrogen diluted ethylene (C2H4) was used as source gas for the deposition of intrinsic a-SiC:H films, and then diborane (B2H6), as the doping gas, is added to C2H4 and SiH4/H2 during the deposition of films. The uniformity of thickness and optical bandgap from large area as-dep. films was at 1.8% and 0.3%, respectively. Heterojunction solar cell with 2 wt%-AZO/p-a-SiC:H/i-a-Si:H/c-Si/Ag structure was fabricated and characterized with diameter of 152.3 mm in this large-area ICP-CVD system. Conversion efficiency of 9.123% was achieved with a practical area of 100 mm x 100 mm, which can show the potentials to the fabrication of the large-area solar cell using ICP-CVD method. PMID- 20358949 TI - Nanoscale thickness and roughness control of gravure printed MEH-PPV layer by solvent printing for organic light emitting diode. AB - In this work, a nanoscale thick organic light emitting MEH-PPV (poly[2-methoxy-5 (2-ethylhexyloxy)-1,4-phenylenevinylene]layer) was realized by gravure printing technology and its roughness was controlled by the solvent printing process. Also, an organic light emitting diode (OLED) was successfully fabricated by the gravure printing of MEH-PPV layers with surface treatments of solvent printing. There is strong demand for high throughput and large area processing technology for the commercialization of OLEDs and the gravure printing process is a good candidate. We applied gravure printing process technology to OLED fabrication in this work. We controlled the thickness of the organic layers by the multi printing technique. To control the roughness of the MEH-PPV organic layer, solvent printing was proposed in this work with various solvent mixture of chloroform, chlorobenzene and 1,2-dichlorobenzene on the top of the gravure printed MEH-PPV layers and a significant reduction in roughness was achieved. We were able to achieve a 51 nm thick and 3.7 nm rough MEH-PPV layer with the gravure printing process and subsequent solvent printing treatment and an OLED was fabricated using the gravure printed organic layers. An improvement of the brightness and efficiency was observed due to the improved roughness of the organic layers. PMID- 20358951 TI - Formation of nanotubule, nanorod and polycrystalline nanoparticles TiO2 by alkaline hydrothermal transformation of anatase TiO2. AB - Nanostructured titanium oxides with various morphologies were prepared through the hydrothermal treatment of TiO2 anatase, using LiOH, NaOH and KOH as a peptizing agent at 400 K for 30 hrs. The obtained samples were characterized using the scanning electron microscopy, transmission electron microscopy, X-ray diffraction, BET measurement and the electron spin resonance spectroscopy. The observed morphologies such as tubule, partially plugged nanorod and polycrystalline nanoparticles can be tailored depending on the types of alkali metal ion, Na+, K+, and Li+ used in the hydrothermal treatments. The result of the ESR studies suggested the existence of paramagnetic sites on the annealed nanostructured TiO2 samples. The ESR signals came from the single electron trapped in oxygen vacancy (SETOV) and Ti3+. PMID- 20358950 TI - Synthesis, characterization, and photocatalytic activity of TiO2/SiO2 nanoparticles loaded on carbon nanofiber web. AB - TiO2/SiO2 catalysts were loaded on carbon nanofibers (CNF) support by sol-gel preparation and followed by a dip-coating and heat treatment up to 900 degrees C in inert atmosphere. The photocatalytic activities of the catalysts (TiO2/SiO2)/CNF were tested by the photocatalytic degradation rate of methylene blue (MB) under UV irradiation. It was found that (TiO2/SiO2)/CNF showed a higher photocatalytic activity than TiO2/CNF only. It was analyzed that SiO2 contributed to an increase the photo catalytic activity by suppressing the phase transformation of the TiO2 crystals from anatase to rutile on the heat treatment up to 900 degrees C. PMID- 20358952 TI - Microscopic evidence of a new 9R-AgI polytype heterostructure. AB - The extraordinary high ionic conductivity and the phase transition with large thermal hysteresis of AgI:Al2O3 nanocomposites can be ascribed to the presence of unusual polytype 7H and 9R modification of AgI as mesoscopic heterostructures. In addition to the 7H AgI phase in the composites previously identified by a Rietveld analysis of X-ray diffraction, a new 9R AgI polytype with a characteristic three-fold contrast was directly evidenced by high resolution transmission electron microscopy. The epitaxial intergrowth of various polytypes was also microscopically evidenced which is in accordance with the Rietveld analysis. PMID- 20358953 TI - Growth of TiO2 nanorods on a Ta substrate by metal-organic chemical vapor deposition. AB - TiO2 nanorods were successfully grown on Tantalum (Ta) substrates using titanium tetra isopropoxide (TTIP) as a single precursor without any carriers or bubbling gases. For characterization of the TiO2 structures, scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were employed. For substrate temperatures below 800 degrees C, a rough film structure without nanorods could be found. However, at a sample temperature of 800 degrees C, nanorod structures with a respective diameter and length of 0.1 approximately 0.2 microm and 0.7 approximately 1.5 microm, respectively, could be synthesized. The nanorods exhibited a rutile phase with a 2:1 stoichiometry of O:Ti, identified using XRD and XPS. When the growth temperature exceeded 800 degrees C, agglomeration of the nanorods was identified. PMID- 20358954 TI - Fabrication and ink-jet patterning of copper nanoparticles with improved dispersion stability. AB - Copper (Cu) nanoparticles as the metal nanoparticles in the conductive ink were synthesized using electrochemical reaction. This method is characterized as the synthesis process without any metal salts and the post-treatment of washing and drying. It means that it does not need to consider about oxidized and agglomerated metal nanoparticles during the extra treatments. The Cu nanoparticles were synthesized in the various conditions of electrolyte to investigate the mechanism of the synthesis reaction of Cu nanoparticles. And also, the synthesized Cu nanoparticles were controlled the dispersion stability with the addition of dispersion agent such as PVP and Dextran. Finally, it was achieved the ink-jet printed Cu patterns using the synthesized Cu nanoparticles, and examined the morphology of the patterns. PMID- 20358955 TI - Characteristics of Ge-Sb-Te films prepared by cyclic pulsed plasma-enhanced chemical vapor deposition. AB - Ge-Sb-Te (GST) thin films were deposited on TiN, SiO2, and Si substrates by cyclic-pulsed plasma-enhanced chemical vapor deposition (PECVD) using Ge{N(CH3)(C2H5)}, Sb(C3H7)3, Te(C3H7)3 as precursors in a vertical flow reactor. Plasma activated H2 was used as the reducing agent. The growth behavior was strongly dependent on the type of substrate. GST grew as a continuous film on TiN regardless of the substrate temperature. However, GST formed only small crystalline aggregates on Si and SiO2 substrates, not a continuous film, at substrate temperatures > or = 200 degrees C. The effects of the deposition temperature on the surface morphology, roughness, resistivity, crystallinity, and composition of the GST films were examined. PMID- 20358956 TI - Synthesis and electrochemical properties of LiMPO4 (M = Fe, Mn, Co) nanocrystals in polyol medium. AB - Olivine structured LiMPO4 (M = Fe, Mn, Co) was synthesized by the solvothermal process using a polyol medium of diethylene glycol (DEG) without any further heating as a post procedure. The synthesized LiMPO4 nanoparticles exhibited an average length of 200 approximately 400 nm, width of 200 approximately 300 nm, and thickness of 20 approximately 50 nm, and with well dispersed plate and rod morphologies. The Rietveld-refined X-ray diffraction (XRD) pattern of LiFePO4 exhibited a good fit with an olivine structure (space group: Pnma) and no undesirable impurity phases. The LiFePO4 nanocrystals showed a reversible capacity of 167 mAh/g, equating to a utilization efficiency of 98% of its theoretical capacity, with a good cyclability over an extended range up to 40 cycles. PMID- 20358957 TI - Effects of catalyst on the super-growth of multi-walled carbon nanotubes. AB - We investigated the effects of catalyst (Fe)/buffer layer (Al2O3) on the vertical growth multiwalled carbon nanotubes (CNTs) synthesized by thermal chemical vapor deposition. The Fe was deposited onto Al2O3/SiO2/Si wafer by using e-beam evaporator. Ethylene was used as a feeding gas while argon was used as a carrier gas. Hydrogen was also introduced. The catalyst layers were optimized to control the length, diameter, purity, and alignment of CNTs. For the optimized conditions we produced vertically aligned CNTs of about 1 cm in length during 10 h. The effects of catalysts on nanotube characteristics were systematically analyzed using SEM, TEM, and Raman measurement. PMID- 20358959 TI - Morphology and properties of sulfonated poly(styrene-b-(ethylene-co-butylene)-b styrene)/ poly(4-styrene sulfonic acid) blends filled with multiwalled carbon nanotubes. AB - Nanocomposites based on poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) and multiwalled carbon nanotubes (MWNTs) were prepared. In order to facilitate the dispersion of MWNTs in the nanocomposites, the pristine MWNTs were reduced by Li to anions and SEBS was sulfonated. Poly(4-styrenesulfonic acid) (PSSA) was also added to either SEBS or S-SEBS and the morphology and properties of the nanocomposites were examined. Nanocomposites prepared from S-SEBS, PSSA, and the modified MWNTs showed a threshold decrease in electrical resistivity due to the percolation of MWNTs at a critical MWNT content (P(c)) lower than those for the nanocomposites based on SEBS, PSSA, and the MWNTs. It was found that the P(c) decreased with increasing the concentration of PSSA in the nanocomposites containing S-SEBS. The efficient percolation of MWNTs in the S-SEBS/PSSA nanocomposites was attributed to interactions between the ionic moieties of MWNTs and S-SEBS and the fine dispersion of the MWNTs. Nanocomposites based on S-SEBS showed large increase of rubbery plateau modulus compared with those based on SEBS. PSSA played the role of plasticizer of sulfonated PS blocks above T(g) of PS blocks in S-SEBS. PMID- 20358958 TI - Biodegradable nano-polymeric system for efficient Akt1 siRNA delivery. AB - Biodegradable nano-polymeric carrier composed of polycaprolactone (PCL) and polyethylenimine (PEI) (BNPP) was successfully synthesized for the delivery of sh/siRNA in lung cancer cells. BNPP efficiently and safely delivered siRNA in lung cancer cells. BNPP-delivered Akt1 siRNA silenced Akt1 protein, and reduced the cancer cell survival, proliferation, malignancy and metastasis. PMID- 20358960 TI - Smart particles for noble drug delivery system. AB - Optically encoded smart particles were prepared for noble drug delivery materials. Distributed Bragg reflector (DBR) porous silicon (PSi) was generated by applying a computer-generated pseudo-square wave current waveform. This DBR PSi film was lifted off from the Si substrate and thermally oxidized to convert PSi to porous silicon dioxide (PSD). DBR PSD film was derivatized with 20(S) Camptothecin (CPT) and fractured by ultrasono-method to give smart particles. DBR PSD smart particles exhibited a sharp photonic band gap in the optical reflectivity spectrum. Optical characteristic of PSD smart particles retained DBR photonic property in aqueous buffer solution. The release of CPT and change of reflection wavelength were measured by UV-vis and reflectance spectrometer, respectively. The intensity of differential peak from reflection resonances of the smart particles was increased with a drug release. The blue shift of reflection peak resulted in the decrease of refractive index of PSD smart particles during the drug release. The concentration of released drug exhibited an linear relationship with a release time. PMID- 20358961 TI - Uniform and reproducible barrier layer removal of porous anodic alumina membrane. AB - A method for the fabrication of porous anodic alumina (PAA) membrane without bottom barrier layer on Al substrate is described. In this method, two-step anodizing followed by a barrier thinning process at the end of the second anodization was used to prepare wide range highly-ordered PAA membrane with a thin barrier layer. Finally, cathodic polarization and pore widening processes were combined to remove the barrier layer completely between the oxide film and Al substrate. Scanning electron microscope (SEM) was used to characterize the morphology and structure of the PAA membrane. From the SEM images, the PAA membrane prepared with the assistance of cathodic polarization showed more homogeneous pore diameters and pore wall quality than that made by pore widening only. In addition, the barrier layer was removed completely with 7.5 min of cathodic polarization and 70 min of pore widening without corrosion in the Al substrate. It was possible to control the pore diameter without any damage to the PAA template from 70 to 90 nm. The fabricated PAA template can be applied to the growth of ordered nanowires, nanorods, nanotubes, and similar structures. PMID- 20358962 TI - High sensitive NO2 gas sensor with low power consumption using selectively grown ZnO nanorods. AB - The noble gas sensor using multiple ZnO nanorods was fabricated with CMOS compatible process and sol-gel growth method on selective area and gas response characteristics to NO2 gas of the sensor device were investigated. We confirmed the sensors had high sensitive response denoted by the sensitivity of several tens for NO2 gas sensing and also showed pretty low power consumption close to 20 mW even though the recovery of resistance come up to almost the initial value. PMID- 20358963 TI - Evolution of nano-grains in high purity copper by accumulative roll-bonding process. AB - The evolution of nano-grains in oxygen free copper with accumulative roll-bonding is investigated by TEM and EBSD analysis. The ultrafine grains developed in the sample after 8-cycle ARB. It was found that the mean spacing of grain boundaries, which was 63 microm in initial material, reduced to 5.5 microm after 1 cycle, then surprisingly 450 nm after 3 cycles. In addition, the fraction of high-angle boundaries in the sample after 1-cycle ARB was 0.32, but it after 3-cycle ARB was surprisingly more than 0.6. Texture development of the ARB processed samples is different depending on the number of ARB cycles. PMID- 20358964 TI - Growth factors for silver nanoplates formed in a simple solvothermal process. AB - We synthesized both big and ultra-small silver nanoplates through a simple solvothermal process in a common autoclave. Using this approach, we achieved the reduction of silver nitrate in DMF or ethanol in the presence of PVP as a capping agent. The reduction capacity of PVP was also investigated. Growth factors such as the concentration of silver precursor, quantity of capping agent, reaction time, and temperature have been shown to play important roles in the formation of different sizes and shapes of silver nanoplates. The big plates, over 100 nm in edge length, were found mainly in the shape of a connected triangular. Single triangle plates, truncated triangular plates, and hexangular plates were also found under different reaction conditions. The ultra-small silver nanoplates, 20 100 nm in edge length, were successfully extracted from the solution under different centrifugation conditions. The UV-vis spectrum exhibited intense in plane dipole absorption peaks varying from 470-630 nm, as reflected by the gradual color change of the solution from orange to red, and finally to blue. PMID- 20358965 TI - Molybdenum and tungsten promoted carbons for use as catalyst supports in methanol electro-oxidation. AB - Two types of the molybdenum and tungsten promoted carbons (MWCs) were prepared by the successive impregnation and co-impregnation of molybdenum and tungsten precursors on carbon black with a heat treatment. The resulting MWCs were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and electrochemical techniques and evaluated as a catalyst support for a Pt catalyst in methanol electro-oxidation. MWC-S, prepared by successive impregnation, showed a well developed carbidic phase with a large portion of tungsten carbide phase. In contrast, MWC-C, prepared by co-impregnation, had a lower amount of carbidic carbon and larger fraction of molybdenum carbide phase. MWCs-supported Pt catalysts showed higher catalytic activities than the Pt catalyst on pure carbon black in both CO oxidation and methanol electro oxidation. In particular, Pt/MWC-S exhibited the highest performance among the Pt catalysts employed in this work. The high activity of Pt/MWC-S can be attributed to the positive effect of molybdenum-tungsten carbide phase, which promotes the activation of water and the removal of intermediate CO species. PMID- 20358966 TI - Characterization and morphology of prepared titanium dioxide nanofibers by electrospinning. AB - Dispersed titanium dioxide in polymer nanofibers were prepared by sol-gel processing and electrospinning techniques using titanium isopropoxide (TiP)/polyvinylpyrrolidone (PVP) solution. The prepared titanium dioxide nanofibers were characterized by FE-SEM, TEM, XRD, and FT-IR. Pure titanium dioxide nanofibers were obtained from calcination of inorganic-organic composite fiber. The diameter of titanium oxide nanofibers were in the range of 70 nm to 150 nm. Prepared titanium dioxide nanofibers show rough surface and rather small diameter compare with TiP/PVP composite nanofibers. After calcined at 500 degrees C, TiO2 nanofibers convert into anatase and rutile mixed phased from amorphous structure. Calcination of these composite fibers above 600 degrees C resulted in pure rutile TiO2 nanofibers. PMID- 20358967 TI - Effect of microstructure on thermal conductivity of Cu, Ag thin films. AB - Thin film type materials are widely used in modern industries, such as semiconductor devices, functional superconductors, machining tools, and so on. The thermal properties of material in semiconductor are very important factors for stable operation because the heat generated during device operation may increase clock frequency. Even though thermal properties of thin films may play a major role in assessing reliability of parts, the measurement methods of thin film thermal properties are generally known to be complex to devise. In this study, a temperature distribution method was applied for the measurement of thermal conductivity of Cu and Ag thin film on borosilicate glass substrate. Cu and Ag thin films were deposited on borosilicate glass using thermal evaporation processes. To measure the thermal conductivity changes according to the microstructure of metallic thin film, the processing variables for the Cu and Ag thin film deposition were changed. To minimize the effect of film thickness, the film thickness was fixed to the thickness of approximately 500 nm throughout experiments. The thermal conductivities of thin films were measured to be much lower than those of bulk materials. Thin film with larger grain size showed higher thermal conductivity probably due to the lower number density of grain boundary. Weidman-Franz law could be applied to thin films produced in this study. Thermal conductivity was also estimated from the resistivity of thin film and Lorenz number of bulk material. PMID- 20358968 TI - Effect of bath temperature on the properties of nanocrystalline ZnO thin films. AB - The nanocrystalline zinc oxide (ZnO) thin films have been prepared by chemical bath deposition (CBD) method from aqueous zinc nitrate solution at room temperature (25 degrees C) and at higher temperature (75 degrees C). The changes in structural, morphological and optical properties were studied by means of X ray diffraction (XRD), scanning electron microscopy (SEM), and optical absorption. The structural studies revealed that the film deposited at room temperature showed mixed phases of ZnO and Zn(OH)2 with wurtzite and orthorhombic crystal structure whereas at higher temperature, the deposited film is ZnO with wurtzite crystal structure. After air annealing at 400 degrees C, all the films converted into pure ZnO with wurtzite crystal structure. The films deposited at room temperature showed fibrous surface morphology with interconnected flakes while films deposited at higher temperature shows well-developed nano-rod morphology. Optical study shows that band gap energy (E(g)) of as-deposited thin films deposited at room temperature and at higher temperature are 3.81 and 3.4 eV, decreases up to 3.20 eV, after annealing treatment. PMID- 20358969 TI - Synthesis and electrochemical properties of LiFePO4/carbon nanocomposites in polyol medium. AB - LiFePO4/Carbon nanocomposites with varying amounts of carbon were synthesized using polyol process without any further heating as a post step. The X-ray diffraction patterns of all samples were indexed on the basis of orthorhombic olivine-type structure. The field emission-TEM images of composites with the amount of 3 approximately 15 wt% carbon showed the average sizes of 45 approximately 80 nm with nanorod shape surrounded by carbon. The initial discharge curves of LiFePO4/Carbon show 166, 157, 142, and 119 mAh/g capacities at a current density of 0.1 mA/cm2 in the voltage range of 2.5-4.2 V, respectively, without capacity fading and excellent cycle retentions during the 20 cycles. Especially, the sample of amount of 3 wt% carbon shows the excellent high rate performances at 15 and 30 C rates with high capacity retention compared with previously reported results of high temperature processed results, due to the existence of conductive agents such as carbon which suppresses particle growth and exhibits improved electronic conductivity and lithium ion diffusivity, simultaneously. PMID- 20358970 TI - Synthesis and characterization of iridium complexes bearing substituted 2,2' bipyridyl and 2-pyridylphenyl ligands for photoluminescence. AB - The reaction of [Ir(ppy)2(micro-Cl)]2 (ppy = 2-pyridiylphenyl) with a substituted bpy ligand (5-bromo-2,2'-bipyridiyl, 5,5'-dibromo-2,2'-bipyridiyl, 5-ethynyl-2,2' bipyridiyl) affords [Ir(ppy)2R-(bpy)-R'](CIO4) (R = H, R' = Br (1); R = R, R' = Br (2); R = H, R' = ethynyl (3)) in high yield. The structural, physical, and electrochemical properties of the iridium complexes 1, 2, and 3 were characterized by elemental analysis, NMR and optical spectroscopy, cyclic voltammetry, and X-ray structural analysis. PMID- 20358971 TI - Multi-amine-grafted SBA-15 spherical nanoparticles for the adsorption of proteins. AB - Mesoporous silica spheres (SBA-15) have been obtained via a two-step synthesis process by using a triblock copolymer as a template in combination with a co surfactant and co-solvent. Multi-amine-grafted mesoporous silicas were prepared by attaching 3-aminopropyl triethoxysilane, N-2(-aminoethyl)-3 aminopropyltrimethoxysilane and (3-trimethoxysilylpropyl)diethylenetriamine via a post-synthetic method. The proteins used in adsorption experiments include Bovine Serum Albumin (BSA), Lysozyme (LYS) and Myoglobin (MYO). The protein adsorption properties such as equilibrium and kinetics were investigated. The results show that the original SBA-15 samples have the highest adsorption capacity for all proteins due to their largest pore size and internal surface area. PMID- 20358972 TI - Photocatalytic degradation of methylene blue dye under visible light over Cr doped strontium titanate (SrTiO3) nanoparticles. AB - Strontium titanate (SrTiO3) and chromium doped SrTiO3 (Cr/SrTiO3) were prepared by modified sol-gel method with the citric acid as a chelating agent in the ethylene glycol solution for the effective photodegradation of methylene blue dye under visible light irradiation. The synthesized doped and un-doped SrTiO3 nanoparticles were structurally characterized and their photoresponse performances for the efficient degradation of methylene blue dye have been demonstrated. After introducing the Cr on SrTiO3, UV-Vis absorption was appeared the red-shift at 566 nm from 392 nm as compare with bare SrTiO3. The photocatalytic degradation activity of Cr/SrTiO3 was significantly improved to 60% degradation of methylene blue in 3 h under visible light, which is approximately 5 times higher than that of the bare SrTiO3. PMID- 20358973 TI - Orientational relationships and atomic arrangements of GaN nanorods grown on Al2O3 (0001) substrates by using hydride vapor phase epitaxy. AB - Scanning electron microscopy (SEM) images and transmission electron microscopy (TEM) images showed that the one-dimensional GaN nanorods were formed on Al2O3 (0001) substrates by using hydride vapor phase epitaxy without a catalyst. Selected area electron diffraction (SAED) pattern and high-resolution TEM (HRTEM) results showed that GaN nanorods grown on Al2O3 (0001) substrates had crystalline wurzite structures and (0001) preferential orientation. The morphologies of GaN nanorods were affected by the flow rates of the source materials. The orientational relationships between the GaN nanorods and the Al2O3 substrates were (0001)GaN perpendicular (0001) Al2O3 and [0110]GaN perpendicular [1120] Al2O3. Cross-sectional and plan-view atomic arrangements of the fully relaxed interfacial region are described on the basis of the TEM, the SAED pattern, and the HRTEM results. PMID- 20358974 TI - Electrochemical properties of nanoparticle-based Ti-Co-Mg electrodes by mechanical alloying process. AB - The Ti-Co-Mg powders were synthesized by mechanical alloying process. The crystalline structure, particle size, surface morphology and the electrochemical performance of the Ti-Co-Mg alloy electrodes have been characterized by X-ray diffractometer, field emission-scanning electron microscopy, and charge-discharge cycler. PMID- 20358975 TI - Reflective and magnetic properties of photonic polymer composite materials based on porous silicon and magnetite nanoparticles. AB - Photonic polymer composite materials exhibiting both reflective and magnetic properties were prepared by the replication of rugate porous silicon (PS) using polystyrene and magnetite nanoparticle (Fe3O4). Rugate PS prepared by applying a computer-generated pseudo-sinusoidal current waveform resulted in a mirror with high reflectivity in a specific narrow spectral region and served as a template for replicating its nanostructure with polystyrene containing the magnetic nanoparticles of magnetite. The composite films replicated a sharp photonic resonance with full-width at half maximum (FWHM) of 20 nm from rugate PS in the reflectivity spectrum as well as displayed a magnetic property of magnetite nanoparticles in SQUID magnetometry. Optical characteristics of composite films indicated that the surface of polymer film had a negative structure of rugate PS. The composite films were stable in aqueous solutions for several days without any degradation. PMID- 20358976 TI - Electrical impedance properties of carbon nanotube composite electrodes for chemical and biosensor. AB - Electrical impedance properties of different type of carbon nanotubes based bulk electrodes have been investigated to develop chemical and biosensors. The bulk composite electrodes were fabricated with single-wall and multi-wall carbon nanotubes involving ionic conducting host polymer, Nafion, by using traditional solution-casting techniques. Under the various amounts of buffer solution, resistance and capacitance of the electrodes were measured with LCR meter and their characteristics due to ionic conducting host polymer were investigated by means of electrokinetic analysis. The capacitance values showed drastic change while the resistances only changed within few percent ranges. Electrical impedance measurement provided rapid and simple sensing mechanism to develop chemical sensor and biosensors with bulk nano electrodes. PMID- 20358977 TI - Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. AB - The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism. PMID- 20358978 TI - Improvement of the stability of hydroxyapatite through glass ceramic reinforcement. AB - Hydroxyapatite has achieved significant application in orthopedic and dental implants due to its excellent biocompatibility. Sintered hydroxyapatites showed significant dissolution, however, after their immersion in water or simulated body fluid (SBF). This grain boundary dissolution, even in pure hydroxyapatites, resulted in grain separation at the surfaces, and finally, in fracture. In this study, hydroxyapatite ceramics containing apatite-wollastonite (AW) or calcium silicate (SG) glass ceramics as additives were prepared to prevent the dissolution. AW and SG glass ceramics were added at 0-7 wt% and powder-compacted uniaxially followed by firing at moisture conditions. The glass phase was incorporated into the hydroxyapatite to act as a sintering aid, followed by crystallization, to improve the mechanical properties without reducing the biocompatibility. As seen in the results of the dissolution test, a significant amount of damage was reduced even after more than 14 days. TEM and SEM showed no decomposition of HA to the secondary phase, and the fracture toughness increased, becoming even higher than that of the commercial hydroxyapatite. PMID- 20358979 TI - Effect of deposition temperature on the characteristics of HfN(x) thin films prepared by plasma assisted cyclic chemical vapor deposition. AB - This study examined the resistivity, composition and crystallinity of chemically vapor-deposited HfN(x) films deposited using tetrakis(dimethylamido)hafnium and plasma activated hydrogen as a function of the deposition temperature. The film growth rate (thickness/cycle) ranged from 0.09-0.15 nm/cycle depending on the deposition temperature. The deposition rate was initially insensitive to the substrate temperature at 150-200 degrees C but increased significantly at higher temperatures. The carbon impurities in the films were in the range of approximately 17 to 18 at% and formed Hf-C bonds. All the deposited films were polycrystalline, regardless of the deposition conditions, with a (111) preferred orientation. High substrate temperatures tended to yield films with low resistivity that was relatively constant at temperatures above 225 degrees C. PMID- 20358980 TI - Releasing properties of proteins on SBA-15 spherical nanoparticles functionalized with aminosilanes. AB - Based on morphology of SBA-15 particles, each has its own synthetic procedure and characteristics, resulting in different adsorption capacity as well as application in drug delivery system. This study focused on the synthesis mesoporous material SBA-15 with spherical morphology. The synthesized mesoporous silica SBA-15 were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), fourier transform infrared (FT-IR), and BET analysis. The release study of original and modified samples were carried out to assess application for controlled drug delivery system. The adsorbed proteins can be readily desorbed on amine-modified samples. Especially, the diamine-modified sample has the highest release amount for two proteins, Lysozyme (LYS) and Myoglobin (MYO). PMID- 20358981 TI - Relative humidity effect on the preparation of porous electrospun polystyrene fibers. AB - Porous polystyrene (PS) fibers were prepared by relative humidity control during electrospinning process. The relative humidity and solvent mixing ratio strongly affect the surface morphology and average diameter of electrospun PS fibers. In the circumstance of 30% relative humidity at MC/EtOH (90/10, v/v), pores did not form on the surface of polystyrene fibers. However, as the relative humidity increased to 60%, pores appeared on the fiber surface at the same composition of solvent. In comparison, solvent ratio of MC/EtOH (80/20, v/v) gave rather smooth surface of PS fibers. When the MC/EtOH ratio are 90/10 (v/v) and 80/20 (v/v), electrospun PS fibers with minimum average diameter of 5,211 nm (SD = 1,986) and 5,315 nm (SD = 1,039) were prepared. Surface area and average pore size are found to be 30.7 m2/g and 8.7 nm, respectively, with the relative humidity of 40%. PMID- 20358982 TI - Synthesis and characterization of a fluorescent water-soluble paclitaxel prodrug. AB - A fluorescence susceptible water-soluble paclitaxel was synthesized by a condensation reaction between PEGylated paclitaxel (namely, PP7) and 1-pyrene butyric acid (PBA) in order to obtain a better understanding of the mechanism of action of paclitaxel as well as of the environment of the paclitaxel-binding site. The reaction was performed successfully and the resulting paclitaxel was characterized by FT-NMR, analytical-HPLC, UV spectro photometry, and fluorescence spectrometry. The synthesized paclitaxel analogue showed a high susceptibility to fluorescence in both excitation and emission spectra. And we have investigated the time-resolved fluorescence behavior of them in different solvents and at different excitation wavelengths. PMID- 20358983 TI - Electrical characteristics and doping mechanism of DNA molecules doped with iodine solutions. AB - This study examined the electrical characteristics of deoxyribonucleic acid (DNA) molecules doped with iodine solution and their chemical state changes before and after doping. The experiments were progressed in each lambda (A), poly(dA) poly(dT) and poly(dG)-poly(dC) DNA under the same conditions. The authors prepared 20 nm gap Au/Ti electrodes fabricated by e-beam lithography. DNA solutions were dropped on the nano gap of the electrodes and DNA films were formed by drying in a vacuum. DNA films were doped with an iodine solution dissolved in methanol. The authors measured the electrical conductivity of DNA molecules as the number of iodine doping times in 10(-2) torr vacuum. As increase of the iodine solution doping number, the electrical conductivity of three sorts of DNA molecules was remarkably improved respectively. X-ray photoelectron spectroscopy (XPS) was performed to inspect the electrical conduction mechanism that holes on DNA nitrogen region were generated by transferring electrons to iodine molecules. PMID- 20358984 TI - Temperature dependence of bis(triisopropylsilylethynyl)-pentacene nanofilm deposited on octadecyltrichlorosilane self assembled monolayer surface as a transistor channel. AB - Highly pure 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-PEN) nanofilms were deposited on a hydrophobic OTS-SAM surface at two different substrate temperatures (70 degrees C and 90 degrees C) via the vacuum thermal evaporation (VTE) method. X-ray reflectivity measurements over a wide temperature range (30 degrees C-284 degrees C) revealed that out-of-plane crystallinity of the film (approximately 10 nm) remains intact but in-plane crystallinity starts to become poor from approximately 100 degrees C, and to become much more worse from 260 degrees C. Atomic force microscope images showed that TIPS-PEN films (approximately 55 nm) prepared at the substrate temperature of 90 degrees C or above commonly have a number of huge cracks between enormous crystal domains (up to 3 microm) whereas the films didn't form such morphology below T(s) = 90 degrees C. These results clearly suggest that an optimum substrate temperature of TIPS-PEN nanofilms on OTS-SAM surface must be somewhere between 70 degrees C and 90 degrees C, and the process temperature must be kept below 90 degrees C in order to form and maintain a highly crystalline film for an organic thin film transistor device since in-plane crystallinity of a semiconductor channel deeply affects the performance of a transistor. PMID- 20358985 TI - Characterization of nanoporous cavity of quardruply bridged calix[6]arenes by means of hyperpolarized 129Xe NMR. AB - The bridged calix[6]arenes, which are well known as cavitands to capture ions and molecules, were characterized via the hyperpolarized 129Xe NMR. Also, we could deduce the pathway of a guest molecule into hosts and estimate the pore diameter of bridged calix[6]arenes. The characterized results of nanoporous cavity by the hyperpolarized 129Xe NMR corresponded with the measurement from the X-ray structure. This study showed that the hyperpolarized 129Xe NMR could be used as a promising tool to characterize nanoporous cavity of host compounds with low surface area. PMID- 20358986 TI - Effect of surface passivation on dielectrophoresis-prepared multi-channel ZnO nanowire field effect transistor (FETs). AB - We report on the effect of surface passivation on the electrical characteristics of multi-channel ZnO nanowire field-effect transistors (FETs). Surface passivation was performed using a SiO2 layer on ZnO nanowires. Multi-channel FETs were prepared by assembling as synthesized ZnO nanowires on a SiO2/Si substrate using an alternating current (AC) dielectrophoresis (DEP) technique. We observed that surface passivation with a SiO2 layer on ZnO nanowires was significantly affected by electrical characteristics of multi-channel ZnO nanowire FETs such as the threshold voltage and transconductance. PMID- 20358987 TI - Carbon nanotube (CNT)-polymethyl methacrylate (PMMA) composite electrolyte for solid-state dye sensitized solar cells. AB - A novel carbon nanotube (CNT)-polymethyl methacrylate (PMMA) composite electrolyte was successfully synthesized by the thermal polymerization of methyl methacrylate (MMA) with CNTs for solid-state dye sensitized solar cells (DSSCs). The prepared CNTs-PMMA composite electrolytes were characterized by Fourior transformed-infrared (FT-IR) spectroscopy, field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and ionic conductivity. A strong bonding was observed between CNT and PMMA through ester bonding in the CNT-PMMA composite, resulting in the lowering of crystallinity and increasing the ionic conductivity of composite electrolyte. DSSCs fabricated with CNTs-PMMA composite electrolytes achieved relatively high conversion efficiency of 2.9% with an open circuit voltage (V(oc)) of 0.567 volt, short circuit current (I(sc)) of 8.9 mA/cm2 and fill factor of 61.8%, which is attributed to enhanced amorphicity and ionic conductivity due to the formation of strong bonding between CNT and PMMA molecules. PMID- 20358988 TI - Enhancement of the memory effects for nonvolatile memory devices fabricated utilizing ZnO nanoparticles embedded in a Si3N4 layer. AB - ZnO nanoparticles embedded in a Si3N4 layer by using spin-coating and thermal treatment were fabricated to investigate the feasible applications in charge trapping regions of the metal/oxide/nitride/oxide/p-Si memory devices. The magnitude of the flatband voltage shift of the capacitance-voltage (C-V) curve for the Al/SiO2/ZnO nanoparticles embedded in Si3N4 layer/SiO2/p-Si memory device was larger than that of Al/ZnO nanoparticles embedded in SiO2 layer/p-Si and Al/SiO2/Si3N4/SiO2/p-Si devices. The increase in the flatband voltage shift of the C-V curve for the Al/SiO2/ZnO nanoparticles embedded in Si3N4 layer/SiO2/p-Si memory device in comparison with other devices was attributed to the existence of the ZnO nanoparticles or the interface trap states between the ZnO nanoparticles and the Si3N4 layer resulting from existence of ZnO nanoparticles embedded in the Si3N4 layer. PMID- 20358989 TI - Thermal characteristics of a transparent film heater using single-walled carbon nanotubes. AB - This article presents thermal characteristics of a transparent thin-film heater made of single-walled carbon nanotubes on a glass substrate. A simplified analysis model is developed for predicting the thermal behaviors of the heater and its validity is verified by numerical and experimental results. The analytic solution discloses that the key factors controlling steady thermal performance and transient thermal adjustment. For a thin heater of which the Biot number is very small, the temperature of the heater is determined by the applied gradient of electric potential, the sheet resistance of the nanotube film, and the surface heat transfer coefficient. The time scale required for transient heat-up is a function of the thermal mass of glass substrate and the surface heat transfer coefficient. PMID- 20358990 TI - Prevention of coalescence during annealing of FePt nanoparticles assembled by convective coating. AB - FePt nanoparticle suspension was synthesized by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine. The composition of the synthesized nanoparticles was Fe40Pt60. To prevent the coalescence during annealing of FePt nanoparticles we tried two steps of convective coating, where first coating was for silica particle assembly on a silicon substrate and second one was for FePt nanoparticles on the silica layers. It was observed by scanning electron microscopy that FePt nanoparticles were dispersed on the silica surface. After being annealed at 700 degrees C for 30 minutes under nitrogen atmosphere, the particle size of FePt nanoparticles increased slightly from 4 nm to 6 nm but dispersity of the nanoparticles was maintained. Magnetic hysteresis of Fe40Pt60 nanoparticles coating on silica layer after annealing showed typical characteristics of hard magnetic materials, and no incorporation of soft magnetic materials. It was suggested that convective self-assembly with the parallel use of pre-coating that offers solvent flux weakening capillary force between FePt nanoparticles was an effective method to prevent coalescence of nano-sized particles under high temperature annealing. PMID- 20358991 TI - Effect of the growth of nano-sized Pd particle in 1 wt% Pd/gamma-Al2O3 catalyst on the complete oxidation of volatile organic compounds. AB - The effect of growth of nano-sized Pd particle on the catalytic activity of 1 wt% Pd/gamma-Al2O3 catalyst were examined to obtain the complete oxidation of volatile organic compounds (VOCs: toluene, xylene). Fresh and used forms of 1 wt% Pd/gamma-Al2O3 catalysts were characterized by using X-ray photoelectron microscopy (XPS), Transmission electron microscopy (TEM), and Brunauer Emmett Teller (BET) surface area analyses. Catalytic activity tests revealed that the conversion of VOCs increased with the lapse of reaction time at certain reaction temperature. The results of the instrumental analyses and the catalytic performance indicated that the conversion of VOCs was highly dependent on the growth of nano-sized Pd particle in the catalyst. PMID- 20358992 TI - Photocatalytic degradation of 2,4-dinitrophenol using TiO2 in aqueous solution. AB - A new method was developed to synthesize uniform anatase TiO2 nanocrystals by the hydrolysis of titanium tetraisopropoxide in nitric acid-isopropyl alcohol aqueous solutions at 353 K. The samples were characterized by XRD, TEM, FE-SEM, and specific surface area determination. In this work, the photocatalytic degradation of 2,4-dinitrophenol in the presence of TiO2 using ultraviolet (UV) light source was investigated in a batch reactor. The effects of various factors, namely TiO2, pH, temperature and concentration, on the degradation performance of 2,4-DNP were studied. The photocatalytic degradation of 2,4-DNP follows the pseudo-first-order kinetics. In acidic or alkaline conditions, the photocatalytic degradation efficiency of 2,4-DNP was greater than that in neutral conditions. Thermodynamic studies have also been carried out and values of standard free energy (deltaG degrees), enthalpy (deltaH degrees) and entropy (deltaS degrees) were calculated. PMID- 20358993 TI - In-situ deposition of iron oxide nanoparticles on polyacrylonitrile-based nanofibers by chemico-thermal reduction method. AB - Polyacrylonitrile (PAN)-based nanocomposite fibers were prepared by co precipitation of different amounts of Fe(II) and Fe(III) in an alkaline medium to get iron oxide impregnated nanofibers. Nanofibers web were prepared from blend solution of PAN containing different concentrations (1, 2 and 3 wt%) of ferrous (Fe2+)/ferric (Fe3+) solution in the 1:2 molar ratio in an effort to further improvement of the porosity and thereby, electrical properties. Electrospun fibers containing various concentrations of iron salts were then treated with KOH solution to produce nanosized magnetite particles in situ within the PAN nanofibers by precipitating Fe2+ ions or mixture of Fe2+ and Fe3+ ions. Such nanoscale particles homogeneously dispersed in PAN nanofibers to form the three dimensional network structure. The homogeneously dispersed nanoparticles of iron oxide in and on the PAN carbon nanofibers produced the network structure of reasonably well-aligned configuration. Composite nanofibers morphologies and surface properties were discussed utilizing the combined techniques viz., field emission scanning electron microscope (FE-SEM), particle size analyzer, surface area and pore size distribution measurements. PMID- 20358994 TI - The effect of microwave-assisted for photo-catalytic reaction in aqueous nano TiO2 particles dispersions. AB - In this study, the photo-catalytic degradation of methylene blue in TiO2 particles-dispersed aqueous solution was carried out by irradiating microwave and UV light simultaneously. The results of photocatalytic degradation of methylene blue showed that the decomposition rate increased with the microwave intensity, UV intensity, TiO2 particle dosages and the circulating fluid velocity. From the result of microwave-assisted photo-catalytic degradation of methylene blue, decomposition rate were shown gradually increased according to the increase of pH. The photo-catalytic degradation rate constant obtained under simultaneous irradiation of microwave and UV light case was about 1.5 times higher than irradiation of UV light only case. This result suggests that there is a synergy effect when the constituent techniques are applied together and that the additional irradiation of microwave can play a very important role in photo catalysis of organic water pollutants. PMID- 20358995 TI - Selective aggregation of polyanion-coated gold nanorods induced by divalent metal ions in an aqueous solution. AB - A simple, accurate method for detecting metal ions in an aqueous solution using functionalized gold nanorods (AuNRs) is described. The method involves the complexing of divalent metal ions with poly(acrylic acid) (PAA) and, the localized surface plasmon resonance (LSPR) phenomena of AuNRs. Changes in the longitudinal surface plasmon bands (LSPBs) were monitored using aggregates of PAA coated AuNRs with various divalent metal ions via UV-vis spectroscope. Functionalized AuNRs underwent robust aggregate formation by chelation with divalent metal ions (e.g., Cu2+, Zn2+, Cd2+, and Fe2+). Copper ions formed largest aggregates within 2 h, because complexation between Cu2+ and dicarboxylate has the highest deltaH and -deltaG values. This process represents an easy and useful method for detecting certain divalent metal ions, and the aggregates are also, in some cases, clearly visible to the naked eye. PMID- 20358997 TI - Oxidation of refractory sulfur compounds over Ti-containing mesoporous molecular sieves prepared by using a fluorosilicon compound. AB - Titanium containing mesoporous molecular sieve (Ti-MMS) catalysts were studied for the oxidative desulfurization of refractory sulfur compounds. Ti-MMS catalysts were synthesized from fluorosilicon compounds and Ti with the hydrolysis reaction of H2SiF6 in an ammonia-surfactant mixed solution. The solid products were characterized by XRD, XRF, nitrogen adsorption, and diffuse reflectance UV-vis spectroscopy. Effects of Ti loading and oxidant/sulfur mole ratio, and sulfur species on ODS activity were investigated. PMID- 20358996 TI - Synthesis of bimetallic nanoparticles and their application to growth of multiwalled carbon nanotube forest. AB - We synthesized bimetallic nanoparticles and used them to grow CNTs with an atmospheric-pressure plasma-enhanced chemical vapor deposition system. FePt and FeCo bimetallic nanoparticles were synthesized by the bottom-up high-temperature polyol process using a simple centrifugal method. The diameter of synthesized nanoparticles ranged from 2 to 5 nm with high uniformity, as measured with a transmission electron microscope. The CNTs synthesis was carried out on bimetallic nanoparticles as a catalyst using acetylene as a carbon source gas. The CNT forests grown exhibited a maximum height of 96 microm, which is relatively high compared with other growth technologies. A forest of highly pure multiwalled CNTs with diameters of 10-20 nm was successfully synthesized on a bimetallic nanoparticle catalyzed substrate. As the growth temperature increased, the quality of CNTs improved remarkably, indicating that the graphitization could be controlled by varying the growth temperature. Furthermore, the oxygen plasma pre-treatment of dispersed bimetallic nanoparticles before CNTs growth could contribute to the production of highly pure CNTs. By TEM measurements, we observed that pure multiwall CNTs without defects or amorphous carbon could be synthesized. PMID- 20358998 TI - Induced circular dichroism of gold in the self-assembled polymeric nanoparticles. AB - This study reports that the alkanethiol-capped golds loaded in the self-assembled polymeric nanoparticles exhibit the characteristic induced circular dichroism (ICD) in the near UV absorption region. The core-shell type polymeric nanoparticles composed of poly(y-benzyl L-glutamate) (PBLG) as hydrophobic inner core and poly(ethylene oxide) (PEO) as hydrophilic outer shell were obtained by the diafiltration method after dissolving PBLG/PEO block copolymer in organic solvent. The circular dichroism (CD) of alkanethiol-capped gold nanoparticles as the guest was induced by the chiral PBLG as the host in self-assembled polymeric nanoparticles with Cotton effect in the range of 220-230 nm whose crossing point matched lambda(max) in the UV region of alkanethiol-capped gold nanoparticles. Transmission electron microscopy and electrophoretic light scattering spectrophotometry were used to study the morphology and particle size of gold loaded core-shell type polymeric nanoparticles, respectively. The results indicated that the PBLG chains in the block copolymer and alkanethiol-capped gold nanoparticles were associated together by hydrophobic interaction and chiral PBLG core in the self-assembled polymeric nanoparticles induced CD of the gold. PMID- 20358999 TI - New synthetic route of alkyl-terminated silicon nanoparticles and their optical characteristics. AB - New synthetic route and characterization of alkyl-capped nanocrystalline silicon (R-n-Si) were achieved from the reaction of silicon tetrachloride with sodium/benzophenone ketal, followed by n-butyllithium. Optical characteristics of silicon nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), and photoluminescence (PL) spectroscopy. Butyl-capped silicon nanoparticles exhibited an emission band at 410 nm with excitation wavelength of 360 nm. Average size of n-butyl-capped silicon nanoparticles was obtained by particle size analyzer (PSA) and transmission electron microscopy (TEM). Average size of n-butyl-capped Si nanoparticles was about 6.5 nm. PMID- 20359000 TI - Local structural and optical properties of ZnO nanoparticles. AB - This study examined the local structural and optical properties of ZnO nanoparticles (NPs) with mean diameters of 4.5 and 70 nm using extended X-ray absorption fine structure (EXAFS) measurements at the Zn K edge and photoluminescence (PL) measurements. EXAFS revealed that the average bond length of atomic pairs in the NPs was shorter than that of the powder. Furthermore, a substantial amount of structural disorder existed in the NPs. From the PL measurements, we observed the direct band gap peak of 3.41 eV from the 70 nm ZnO NPs at low temperatures. This blue shift was related to the structural property changes. PMID- 20359001 TI - Preparation and characterization of nanostructured Pt/TiO2 thin films treated using electron beam. AB - Pt nanoparticle-doped titanium dioxide (Pt/TiO2) thin films were prepared on a silicon wafer substrate by sol-gel spin coating process. The prepared thin films were treated with electron beam (EB at 1.1 MeV, 100, 200, 300 kGy) at air atmosphere. The effect of EB-irradiation on the composition of the treated thin films, optical properties and morphology of thin films were investigated by various analytical techniques such as X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE), X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The crystal structure of the TiO2 layer was found to be an anatase phase and the size of TiO2 particles was determined to be about 13 nm. Pt nanoparticles with diameter of 5 nm were observed on surface of the films. A new layer (presumed to be Pt-Ti complex and/or PtO2 compound) was created in the Pt/TiO2 thin film treated with EB (300 kGy). The transmittance of thin film decreased with EB treatment whereas the refractive index increased. PMID- 20359002 TI - Ag-doped multiwalled carbon nanotube/polymer composite electrodes. AB - Two types of carbon nanotube (CNT) based films were fabricated by adsorbing two different types of multiwalled carbon nanotubes (MWCNTs) on bacterial cellulose membrane templates. A bacterial cellulose membrane consists of ribbon-shaped nanofibrils that are arranged to form a porous 3D network. These characteristics lead to the uniform deposition of MWCNTs on the membrane structure and the final CNT based films with high surface areas. Two types of MWCNTs were used: (1) MWCNTs that had been purified by an acid treatment and (2) Ag-doped MWCNTs, which consisted of MWCNTs with Ag nanoparticles attached to their surfaces. The morphologies of the Ag-doped MWCNTs and CNT based films were examined using transmission electron microscopy. In addition, the electrical conductivity and electrochemical properties of the CNT based films were measured using a four point probe and a cyclic voltammeter, respectively. The cyclic voltammetry data showed that the Ag particles attached to the MWCNT surfaces influenced the electrochemical properties of the CNT based films. PMID- 20359003 TI - Electrical and mechanical properties of poly(L-lactide)/carbon nanotubes/clay nanocomposites. AB - An organoclay containing epoxy groups, twice-functionalized organoclay (TFC), was synthesized by reacting (glycidoxypropyl)trimethoxy silane with Cloisite25A (C25A), which had already been modified with an amine compound. The introduction of epoxy groups to the clay surface and carboxylic group-functionalized multiwalled carbon nanotubes (MWCNTs) improved the interfacial adhesion between the poly(L-lactide) (PLLA) and nano-sized fillers when melt-compounded. The PLLA/MWCNTs/TFC nanocomposites showed superior tensile properties to those of PLLA and PLLA/CNTs. The dispersion of MWCNTs in the PLLA matrix decreased the electrical resistivity of the composite substantially due to the higher MWCNT loading. However, the introduction of TFC to the PLLA/MWCNTs nanocomposites resulted in a slight increase in volume resistivity. This increase was attributed to the individual MWCNTs being blocked by the TFC. The clays in the PLLA/MWCNTs/TFC nanocomposites prevented direct contact between the neighboring MWCNTs, which increased the electrical resistivity of the nanocomposites. PMID- 20359004 TI - The effect of nanotubular titanium surfaces on osteoblast differentiation. AB - The biological response of fetal rat calvarial cells on a TiO2 nanotubular surface (Ti-NT) was evaluated by cell viability assay, alkaline phosphatase (ALP) activity and reverse transcription polymerase chain reaction (RT-PCR) analysis. The cell viability assay showed no significant difference between the Ti-NT and smooth titanium surfaces (Ti-S). Ti-NT had better cellular responses with regard to the ALP activity and bone-associated markers, such as bone sialoprotein and osteocalcin mRNA than Ti-S. These results suggest that Ti-NT stimulate the differentiation into osteoblasts of fetal rat calvarial cells, potentially contributing to rapid osseointegration. PMID- 20359005 TI - Effects of the type of solvents on the morphology of styrene-methacrylic acid random copolymers cast onto silicon wafer. AB - The effects of the type of solvents on the aggregation behavior of poly(styrene ran-methacrylic acid) (PSMAA) cast onto silicon wafer were studied using a SEM method. It was found that polystyrene prepared from DMF formed non-spherical aggregates but that PSMAA formed mixtures of ellipsoids and spheres. As the acid content increased, the spheres having a distinct boundary started contacting each other, and the average size of spherical particles decreased. Upon neutralization, the spherical particles became contacted spheres covered with much smaller spheres (ca. 20 nm in their sizes) and formed micro-gels. These results were compared to the data in the previous study of samples obtained from either water or THF. It was observed that the solubility parameters of the copolymers and ionomers, and polarity of solvents were some of key factors that determine the aggregation behavior of the polymers. The volatility of the solvent was also found to be an important factor for the aggregation behavior of polymers. PMID- 20359006 TI - Fabrication of encoded rugate porous silicon interferometer for biosensor. AB - Multi-encoded rugate porous silicon (PSi)-based optical biosensor was developed to specify the biomolecules. Multi-encoded rugate PSi was generated by an electrochemical etching of silicon wafer using an electrode configuration in aqueous ethanolic HF solution. Multi-encoded rugate PSi displayed three very sharp reflection bands whose reflection maxima varied spatially across the PSi. The sensor system studied consisted of a multilayer of PSi modified with biotin. The system was probed with various fragments of an aqueous protein analyte. The sensor operates by measurement of the reflection peaks in the white light reflection spectrum from the PSi layer. When the biotin-derivatized rugate PSi was exposed to protein in phosphate buffer solution (PBS), the molecular binding caused a change of its refractive index is detected as a shift in wavelength of these reflection peaks. A red-shift of reflective spectra were observed, when the biotin-modified rugate PSi was exposed to a flow of protein. PMID- 20359007 TI - Roll-printed organic thin-film transistor using patterned poly(dimethylsiloxane) (PDMS) stamp. AB - The roll-printed gate, source, and drain electrodes of organic thin-film transistors (OTFTs) were fabricated by gravure printing or gravure-offset printing using patterned poly(dimethylsiloxane) (PDMS) stamp with various channel lengths and low-resistance silver (Ag) pastes on flexible 150 x 150 mm2 plastic substrates. Bottom-contact roll-printed OTFTs used polyvinylphenol (PVP) as polymeric dielectric and bis(triisopropyl-silylethynyl) pentacene (TIPS pentacene) as organic semiconductor; they were formed by spin coating or ink jetting. Depending on the choice of roll-printing method, the printed OTFTs obtained had a field-effect mobility of between 0.08 and 0.1 cm2/Vs, an on/off current ratio of between 10(4) and 10(5), and a subthreshold slope of between 1.96 and 2.32 V/decade. The roll-printing using patterned PDMS stamp and soluble processes made it possible to fabricate a printed OTFT with a channel length of between 12 to 74 microm on a plastic substrate; this was not previously possible using traditional printing techniques. The proposed fabrication process was 20 steps shorted than conventional fabrication techniques. PMID- 20359008 TI - Kinetic Monte Carlo (kMC) simulation of carbon co-implant on pre-amorphization process. AB - We report our kinetic Monte Carlo (kMC) study of the effect of carbon co-implant on the pre-amorphization implant (PAL) process. We employed BCA (Binary Collision Approximation) approach for the acquisition of the initial as-implant dopant profile and kMC method for the simulation of diffusion process during the annealing process. The simulation results implied that carbon co-implant suppresses the boron diffusion due to the recombination with interstitials. Also, we could compare the boron diffusion with carbon diffusion by calculating carbon reaction with interstitial. And we can find that boron diffusion is affected from the carbon co-implant energy by enhancing the trapping of interstitial between boron and interstitial. PMID- 20359009 TI - Growth of nanograins in TiO2 nanofibers synthesized by electrospinning. AB - Present study focuses the effect of calcination temperature and its duration on the morphology and growth of nanograins in individual TiO2 nanofibers synthesized by electrospinning method. Polyvinyl acetate and titanium tetraisopropoxide were used as chemical precursors along with other standard solvents in the synthesis process. This study shows that synthesized TiO2 nanofibers are randomly arranged and spreads uniformly over the Si substrate and possess polycrystalline nature consisting of nanograins. Similar to the sintering behavior generally observed in bulk ceramics, the nanograins coalesce and grow under higher calcination temperature and longer calcination time. The activation energy for the growth of nanograins is found to be 47.2 kJ/mol. The dominant growth mechanism changes depending on the stages of calcination. PMID- 20359010 TI - Dependences of the electrical properties on the diameter and the doping concentration of the Si nanowire field effect transistors with a Schottky metal semiconductor contact. AB - A compact model of the current-voltage (I-V) characteristics for the Si nanowire field effect transistor (FET) taking into account dependence of the analytical electrical properties on the diameter and the concentration of the Si nanowire of the FETs with a Schottky metal-semiconductor contact has been proposed. I-V characteristics of the nanowire FETs were analytically calculated by using a quantum drift-diffusion current transport model taking into account an equivalent circuit together with the quantum effect of the Si nanowires and a Schottky model at Schottky barriers. The material parameters dependent on different diameters and concentrations of the Si nanowire were numerically estimated from the physical properties of the Si nanowire. The threshold voltage, the mobility, and the doping density of the Si nanowire and the Schottky barrier height at a metal Si nanowire heterointerface in the nanowire FET were estimated by using the theoretical model. PMID- 20359011 TI - Luminance mechanisms in green organic light-emitting devices fabricated utilizing tris(8-hydroxyquinoline)aluminum/4,7-diphenyl-1, 10-phenanthroline multiple heterostructures acting as an electron transport layer. AB - The electrical and the optical properties in green organic light-emitting devices (OLEDs) fabricated utilizing tris(8-hydroxyquinoline)aluminum (Alq3)/4,7-diphenyl 1,10-phenanthroline (BPhen) multiple heterostructures acting as an electron transport layer (ETL) were investigated. The operating voltage of the OLEDs with a multiple heterostructure ETL increased with increasing the number of the Alq3/BPhen heterostructures because more electrons were accumulated at the Alq3/BPhen heterointerfaces. The number of the leakage holes existing in the multiple heterostructure ETL of the OLEDs at a low voltage range slightly increased due to an increase of the internal electric field generated from the accumulated electrons at the Alq3/BPhen heterointerface. The luminance efficiency of the OLEDs with a multiple heterostructure ETL at a high voltage range became stabilized because the increase of the number of the heterointerface decreased the quantity of electrons accumulated at each heterointerface. PMID- 20359012 TI - Luminance efficiency enhancement in green organic light-emitting devices fabricated utilizing a cesium fluoride/fullerene heterostructure electron injection layer. AB - Enhancement mechanisms of the luminance efficiency in green organic light emitting devices (OLEDs) fabricated utilizing a cesium fluoride (CsF)/fullerene (C60) heterostructure acting as an electron injection layer (EIL) were investigated. The luminance efficiencies as functions of the current density showed that the luminance efficiency in the green OLEDs fabricated utilizing a CsF/C60 heterostructure acting as an EIL was higher than that in the green OLEDs fabricated utilizing a CsF, a Liq, or a C60 single EIL. The interfacial dipole existing at the CsF layer decreased the electron injection barrier, and the stability of the OLEDs with a CsF EIL was enhanced due to the lower diffusion rate of Cs atoms in comparison with Li atoms. The enhancement of the luminance efficiency of the OLEDs with a heterostructure EIL was attributed to the increase in the electron injection. These results can help improve understanding of the enhancement mechanisms of the luminance efficiency in green OLEDs utilizing a CsF/C60 heterostructure acting as an EIL. PMID- 20359013 TI - Enhanced efficiency of dye-sensitized solar cells with novel synthesized TiO2. AB - An anatase TiO2 and three kinds of novel TiO2 nanoparticles were prepared by a hydrothermal method for dye-sensitized solar cells (DSSCs), which were obtained by mixing NaOH (10 M), KOH (14 M) and LiOH (10 M) solution with an anatase TiO2 powder, respectively. The TiO2 working electrodes of DSSCs were prepared and the photoelectric properties of the cells were characterized. The influence of different poly(ethylene glycol) contents in TiO2 films with and without HNO3 treatment on the electron transfer in DSSCs were investigated. It is found that the DSSC with HNO3 (0.002 mol/l)-treated film containing 16.7 wt% PEG shows the higher power conversion efficiency of 6.0%, which was mainly depended on the degrees of TiO2 pore size and uniformity of TiO2 films. PMID- 20359014 TI - Sub-50 nm template fabrications for nanoimprint lithography using hydrogen silsesquioxane and silicon nitride. AB - The sub-50 nm templates are successfully fabricated using hydrogen silsesquioxane (HSQ) and silicon nitride on silicon substrate. The HSQ template is directly patterned by e-beam direct writing. The cured HSQ pattern is used for the template of nanoimprint process. The silicon nitride template is reactively ion etched by ZEP resist mask pattern which is prepared by e-beam direct writing using ZEP resist. The line widths of HSQ templates and ZEP patterns after developments are between 22-30 nm and 24-30 nm, respectively. The line width of silicon nitride templates without performing descum is same as that of the ZEP pattern but shows a rough surface. When plasma descum was performed before RIE, the line width of silicon nitride templates increased from 27 nm to 35 nm and has a clean surface. The HSQ template fabrication results in this study will be promise for sub-nm imprint process. PMID- 20359015 TI - The fabrication and properties of Ag/Ni nanocomposite fluid. AB - In this article, an arc-submerged nanofluid synthesis system is proposed and developed for Ag/Ni nanocomposite fluid fabrication. In the fabrication process, the positive electrode uses an Ag rod and the negative electrode uses a Ni rod, with the two electrodes processed in the dielectric liquid. The nanocomposite fluid generated by the synthesis system is analyzed by morphological analysis, heat transfer analysis, magnetic analysis and the UV-Vis spectrophotometer optical property analysis. Experimental results show that the Ag/Ni nanocomposite fluid has a very high Zeta potential of 45 mV, so that without dispersant it can remain stabile longer than five months. Testing the Ag/Ni nancomposite fluid magnetism by SQUID, shows that paramagnetism appears in the nanocomposite fluid. Moreover, the Ag/Ni nanocomposite fluid preserves both the nickel's magnetic characteristic and silver's absorption capability to visible light. PMID- 20359016 TI - Preparation and characterization of Pt nanoparticles inside nanotubule TiO2. AB - Platinum nanoparticle has been supported on the tubular type titanium oxide using incipient wetness method employing H2PtCl6 as a precursor, where the loading was controlled to 4 wt%. The result of transmission electron micrographs of the sample showed the formation of Pt nanoparticles inside the tubule. The distribution of the particle size was found to be bimodal at ca. 1-2 nm and 5-6 nm, respectively. The former size was limited due to the inner diameter of the nanotubule. The particle size obtained from the hydrogen chemisorption, 1.24 H/Pt ratio was nearly 1 nm assuming spherical particle geometry, which was consistent with the formation of the Pt particle of 1-2 nm. The result suggested that there was no pore blockage for hydrogen since hydrogen can diffuse inside the channel through adsorption-diffusion-desorption on the Pt nanoparticle where the one dimensional channel was blocked with the particle itself. PMID- 20359017 TI - Catalytic conversion of 1,2-dichlorobenzene over mesoporous materials from zeolite. AB - In this study, 1,2-dichlorobenzene (DCB), an important precursor of PCDDs and PCDFs, was chosen as a suitable model compound for the catalyzed deep oxidation of dioxin. The recently developed mesoporous materials from zeolites (MMZ) were used for the first time as a support for an oxidation catalyst. The catalytic oxidation of 1,2-dichlorobenzene over Pt/MMZ was carried out, and the catalytic activity was compared with that of Pt/gamma-Al2O3, Pt/Al-MCM-41 and Pt/Beta catalysts. Pt/MMZ showed the highest catalytic activity among the catalysts tested. Interestingly, the catalytic activity of Pt/MMZ was maintained (> 40%) at low temperatures (250 degrees C) at which the other catalysts showed extremely low activity (< 5%). The high catalytic activity of Pt/MMZ was attributed to both the sufficient acidity and mesoporosity of the MMZ support. PMID- 20359018 TI - Performance of PtPd electrocatalysts in direct methanol fuel cell. AB - PtPd nanoparticles on carbon black were prepared to investigate the role of Pd in the anode and cathode of a direct methanol fuel cell (DMFC). The PtPd catalysts in the anode showed a significantly lower performance than the PtRu catalyst. However, the cell performances of these catalysts in the cathode were comparable to that of the Pt catalyst. From cyclic voltammetry, it was observed that the Pd with the Pt catalyst lowered the peak potential and increased the coulombic charge for oxide reduction on the surface of the catalyst. Also, the Pd catalyst without Pt showed relatively high activity for oxygen reduction reaction. PMID- 20359019 TI - The effect of surface roughness on in-situ intrinsic tensile stress behavior in Cu thin films. AB - Intrinsic stress of Cu thin films, which grows in Volmer-Weber type, is reported to show the three unique stress stages, such as initial compressive, broad tensile and incremental compressive. The tensile stress stage may be related to the volume contraction through grain growth and coalescence to reduce over-piled ad-atom on surface. We observed the in-situ stresses behavior of Cu thin films during deposition using multi-beam curvature measurement system attached to a thermal evaporation device. We adopted the 100 microm Si(111) substrate with different surface roughness. The effect of substrate surface roughness was assessed on in-situ tensile stress. Intrinsic tensile stress increase when substrate surface roughness increase due to the increment of surface area deposited. PMID- 20359020 TI - Effect of fiber orientation and fiber contents on the tensile strength in fiber reinforced composites. AB - The study for strength calculation of one direction fiber-reinforced composites and the study measuring precisely fiber orientation distribution were presented. Need the systematic study for the data base that can predict mechanical properties of composite material and fiber orientation distribution by the fiber content was not constructed. Therefore, this study was investigated what affect the fiber content and fiber orientation distribution have on the strength of composites. Fiber-reinforced thermoplastic composites by changing fiber orientation distribution and the fiber content were made. Tensile strength ratio of 0 degrees direction of fiber-reinforced composites increased being proportional the fiber content and fiber orientation function as change from isotropy (J = 0) to anisotropy (J = 1). But, tensile strength ratio of 90 degrees direction by separation of fiber filament decreased when tensile load is imposed for width direction of reinforcement fiber length direction. PMID- 20359021 TI - Thermally grown ZnO nanosheets for high efficiency dye-sensitized solar cells. AB - High efficiency dye-sensitized solar cells (DSSCs) were fabricated using ZnO nanosheet electrodes. ZnO nanosheets were synthesized on top of fluorine-doped tin oxide (FTO) glass using Zn(OAc)2 as a precursor in the gold catalyzed chemical vapor deposition (CVD) method at a temperature of 800-900 degrees C. The synthesized materials were characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), and Raman and photoluminescence (PL) spectroscopy. Typical DSSCs with ZnO nanosheets achieved moderately good conversion efficiency eta of approximately 2.12% with short-circuit current density J(SC) = 3.56 mA/cm2, open-circuit voltage V(OC) = 0.831 V, and fill factor FF = 71%. The high J(SC) and eta are attributed to high dye absorption through high surface ZnO nanosheets, which increased the light harvesting. The lower recombination rate was also observed in the ZnO nanosheet electrodes, resulting in high values of V(OC) and FF in the DSSCs. PMID- 20359022 TI - Synthesis and characterization of nanocrystalline Gd and Tb co-doped ceria-based electrolyte materials for IT-SOFC. AB - Gd and Tb co-doped Ce0.8Gd0.2-xTb(x)O2-delta (0 < or = x < or = 0.09) nanopowders were synthesized by the combustion method using aspartic acid as fuel. The calcined powders formed a ceria-based single phase with a cubic fluorite structure. In addition, the powders were pure, homogeneous, and nanocrystalline nature, i.e., 20.1-23.4 nm in the calculated crystallite size. The partial incorporation of Tb for Gd caused a decrease in the average grain size of the sintered bodies. The high-quality nanosized Ce0.8Gd0.17Tb0.03O2-delta powders provided a high density, ultra-fine grain size, and high electrical conductivity even at the low sintering temperature of 1300 degrees C. The grain size and density of the Ce0.8Gd0.17Tb0.03O2-delta were approximately 146 nm and approximately 99% of the theoretical density, respectively, allowing enhanced electrical conductivity (0.106 Scm(-1) at 800 degrees C). PMID- 20359023 TI - Catalytic removal of sulfur dioxide from dibenzothiophene sulfone over Mg-Al mixed oxides supported on mesoporous silica. AB - Dibenzothiophene sulfone (DBTS), one of the products of the oxidative desulfurization of heavy oil, can be removed through extraction as well as by an adsorption process. It is necessary to utilize DBTS in conjunction with catalytic cracking. An object of the present study is to provide an Mg-Al-mesoporous silica catalyst for the removal of sulfur dioxide from DBTS. The characteristics of the Mg-Al-mesoporous silica catalyst were investigated through N2 adsorption, XRD, ICP, and XRF. An Mg-Al-mesoporous silica catalyst formulated in a direct incorporation method showed higher catalytic performance compared to pure MgO during the catalytic removal of sulfur dioxide from DBTS. The higher dispersion of Mg as well as the large surface area of the Mg-Al-mesoporous silica catalyst strongly influenced the catalyst basicity in DBTS cracking. PMID- 20359025 TI - Effects of highly ordered TiO2 nanotube substrates on the nucleation of Cu electrodeposits. AB - We investigated the effects of TiO2 nanotube substrates on the nucleation density of Cu during electrodeposition in a solution of CuSO4 and H2SO4 at 50 degrees C compared with those of pure Ti and micro-porous TiO2 substrates. During electrodeposition, the density of Cu nuclei on the TiO2 nanotube substrate increased and the average size of Cu nuclei decreased with increasing anodizing voltage and time for the synthesis of the substrate. In addition, the nucleation density of Cu electrodeposits on the highly ordered TiO2 nanotube substrate was much higher than that on pure Ti and micro-porous TiO2 substrates. PMID- 20359024 TI - Highly size-controlled synthesis of metal nanoclusters by inert-gas condensation for nano-devices. AB - Metal nanoclusters were fabricated by inert-gas condensation in a sputtering reactor. From transmission electron microscopy, it was confirmed that copper nanoclusters with a high degree of monodispersity in size of about 5 nm were successfully produced. The conductance of the percolated nanocluster film was measured. In order to incorporate nano-scale arrangement characterizations in nano-devices being operated in air, aging experiments of the specimen after long time in air were carried. Negative temperature coefficient of resistance suggests that surface native copper oxide in core-shell structured nanoclusters was mainly responsible for the conductance, because copper oxide is known as semiconductor. After aged at higher than 100 degrees C, the conductance at room temperature didn't return to the original value. This irreversible phenomenon might be due to coarsening and/or coalescence of copper nanoclusters. PMID- 20359026 TI - Fabrication of mesoporous cobalt oxide (Co3O4) film by electrochemical method for electrochemical capacitor. AB - Mesoporous cobalt oxide (Co3O4) films were deposited on ITO coated glass substrates by electrodeposition from an aqueous CoSO4 solution using CTAB (cetyltrimethylammonium bromide) as the templating agent. The structures of the synthesized films were characterized by X-ray diffraction, and X-ray photoelectron spectroscopy. The presence of mesoporosity was confirmed by transmission electron microscopy and small angle X-ray diffraction analyses. The mesoporous structures of the synthesized films were found to be strongly dependent on the deposition conditions, such as deposition voltage, deposition time, temperature and concentration of templating agent. Cyclic voltammetry and discharging curves were used to examine the electrochemical properties as a capacitor. The mesoporous films prepared with CTAB templating showed a much higher specific capacitance and current density than the nonporous electrode prepared without CTAB templating. PMID- 20359027 TI - Structural and energetic characterizations of thin multi-walled carbon nanotubes using adsorption isotherms. AB - The structural and energetic heterogeneity of thin multi-walled carbon nanotubes (t-MWCNTs) was evaluated from the adsorption of nitrogen and aromatic compounds (benzene, toluene, and m-xylene). The t-MWCNTs was synthesized through the catalytic vapor deposition and characterized by using nitrogen adsorption desorption isotherm and high-resolution transmission electron microscopy (HRTEM) analyses. The equilibrium adsorption data of aromatic compounds on t-MWCNTs were measured using gravimetric apparatus at three different temperatures (303.15, 313.15 and 323.15 K) and at pressures up to 4.0 kPa. The temperature dependent Toth isotherm model was employed to correlate the experimental adsorption isotherm data. The isosteric heat of adsorption was calculated from van't Hoff equation using the temperature dependent Toth isotherm parameters. The adsorption energy distributions (AEDs) were calculated from adsorption isotherms data of nitrogen and aromatic molecules to investigate the surface energetic heterogeneity of t-MWCNTs. The results of pore size distributions, isosteric heats of adsorption and AEDs revealed that t-MWCNTs have structurally and energetically heterogeneous surface. PMID- 20359028 TI - Effect of complexing agent and annealing atmosphere on properties of nanocrystalline ZnS thin films. AB - The nanocrystalline Zinc Sulfide (ZnS) thin films were prepared on glass substrates by chemical bath deposition (CBD) method using aqueous solutions of zinc acetate, thiourea and tri-sodium citrate in alkaline medium at 80 degrees C. The tri-sodium citrate acts as a complexing agent. The effects of complexing agent and annealing atmosphere (95%N2 + 5%H2S) on structural, morphological and optical properties of ZnS thin films were studied using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and optical absorption. XRD study revealed that single phase ZnS powder was formed in the solution with tri sodium citrate, however, ZnS and ZnO mixed phase powder was formed in the solution without tri-sodium citrate. The films deposited with trisodium citrate showed ZnS with hexagonal wurtzite phase. However, annealed film in (N2 + H2S) atmosphere showed cubic (zincblende) phase. FE-SEM images show that grain size of as-deposited and annealed ZnS films are about 20 nm and 50 nm, respectively. Optical absorption study showed that the films have moderate optical transmission from 65% to 75% in the visible region and the optical band gap energy of as deposited ZnS film is 3.91 eV and it decreases to 3.73 eV after annealing. PMID- 20359029 TI - Efficient preparation and characterization of silver-polyphenylsilane nanocomposites. AB - Silver-polyphenylsilane nanocomposites have been effectively prepared by the dehydrocoupling reaction of phenylsilane (PS, PhSiH3) to polyphenylsilane (PPS, [PhSiH]n) in the presence of silver nitrate. The one-step reduction of Ag(+1) nitrate to stable Ag(0) nanoparticles is mediated by PS, resulting in the formation of Ag-PPS composites. The Ag-PPS nanocomposites were characterized by various analytical techniques such as XRD, TEM, FE-SEM, and solid-state UV-vis. TEM and FE-SEM data clearly show that the silver nanoparticles with the size of < 20 nm are well dispersed throughout the PPS matrix in the nanocomposites. XRD patterns are consistent with those for fcc crystalline silver. The size of silver nanoparticles increased with increasing the relative molar concentration of silver salts added. It was found that in the absence of PS, most of the silver nanoparticles undergo macroscopic precipitation by aggregation, indicating that PPS is essential to stabilize the silver nanoparticles by the complexation of Si H to the silver metal centers. PMID- 20359030 TI - Synthesis and characterization of poly(alkoxysilane)s catalyzed by Co/Ni colloidal nanoparticles. AB - Si-Si/Si-O dehydrocoupling of hydrosilanes with alcohols (1:1.5 mole ratio), catalyzed by group VIII metallocenes Cp2M' (M' = Co, Ni) which converted to Co(O)/nickel(O) colloidal nanoparticles, produced poly(alkoxysilane)s in one-pot in high yield. The hydrosilanes include p-X-C6H4SiH3 (X = H, CH3, OCH3, F), PhCH2SiH3, and (PhSiH2)2. The alcohols include MeOH, EtOH, 'PrOH, PhOH, and CF3(CF2)2CH2OH. The weight average molecular weight of the poly(alkoxysilane)s were in the range of 600 to 8100. The dehydrocoupling reactions of phenylsilane with ethanol (1:3 mole ratio) in the presence of the nanocolloid catalyst gave only triethoxyphenylsilane as product. PMID- 20359031 TI - Nano-sized cobalt based Fischer-Tropsch catalysts for gas-to-liquid process applications. AB - Nano-sized cobalt supported catalysts were prepared for Fischer-Tropsch synthesis in gas-to-liquid (GTL) process. The dependence of crystallite size and reducibility of Co3O4 on the supports were investigated with FTS activity. XRD peaks revealed nano crystallites (< 5.47 nm) of Co3O4 crystallites. TEM showed round shaped particles with size less than 5 nm. Support with higher acidity decreased crystallite size of Co3O4. XRD data of used catalysts showed Co3O4 crystallites smaller than 3.5 nm which do not reduce easily to Co(0) state. The crystallite size of Co3O4 plays a role in its reduction to Co(0). TPR results showed that the reduction temperature shifts to higher temperature due to metal support interaction. The variation in the activity of the catalysts depends on the support which in turn affects the crystallite size, dispersion, reducibility and activity of Co species in Fischer-Tropsch Synthesis (FTS). In this study, Co/Al2O3 showed higher CO conversion than the other catalysts. However, the C5+ production was in order Co/SiO2 (78.1%) > Co/Al2O3 (70.0%) > Co/R_TiO2 (61%) > Co/A_TiO2 (57.5%). PMID- 20359032 TI - A study on modification of nanoporous rice husk silica for hydrophobic nano filter. AB - Nanoporous rice husk silica (RHS) was modified with alkylsilylation reagents, hexamethyldisilazane, diethoxydiphenylsilane, dichlorodimethylsilane and n octodecyltrimethoxysilane. The silica samples were characterized with Raman spectrometer, thermal gravimetric analyzer, scanning electron microscope, nitrogen adsorption measurement and solid state nuclear magnetic resonance spectrometer. Raman spectra of the modified silica showed growth of the peaks of C-H stretching and CH3 bending at approximateluy 3000 cm(-1) and approximately 1500 cm(-1), respectively. Weight losses of 3 approximately 5% were observed in thermo gravimetric profiles of the modified silica. The microscopic shape of RHS, approximately 20 nm primary particles and their aggregates was almost not changed by the modification but there were colligations of the silica particles in the sample treated with dichlorodimethylsilane or diethoxydiphenylsilane. BET adsorption experiment showed the modification significantly decreased the mean pore size of the silica from approximately 5 nm to approximately 4 nm as well as the pore volume from 0.5 cm3/g to 0.4 cm3/g except the case of treatment with n octodecyltrimethoxysilane. 29Si Solid NMR Spectra of the silica samples showed that there were decrease in the relative intensities of Q2 and Q3 peaks and large increments in Q4 after the modification except for the case of bulky n octodecyltrimethoxysilane. From the results, it was concluded that the alkylsilylation reagents reacted with hydroxyl groups on the silica particles as well as in the nano pores while the size of the reagent molecule affected its diffusion and reaction with the hydroxyl groups in the pores. PMID- 20359033 TI - Catalytic sol-gel co-polycondensation of para-substituted phenylsilanes and bis(silyl)phenylene to robust organosilicas using colloidal nickel nanoparticles. AB - The dry sol-gel co-polycondensation at toluene in ambient air atmosphere of p-X C6H4SiH3 (X = H, CH3, CH3O, F, Cl) and p-H3Si-C6H4SiH3 (9:1 mole ratio) to co silicas (p-X-C6H4SiO1.5)9(p-O1.5Si-C6H4SiO1.5)1 in high yield, catalyzed by colloidal nickel nanoparticles in-situ generated from nickelocene(II) is described. The co-gels (p-X-C6H4SiO1.5)9(p-O1.5Si-C6H4SiO1.5)1 with higher molecular weights and TGA residue yield were obtained when compared to the homogels p-X-C6H4SiO1.5 Some degree of unreacted Si-H bonds still remained in the gel matrix because of steric bulkiness. All the insoluble gels adopt an amorphous structure with a smooth surface. A plausible mechanism for the dry sol-gel reaction was provided. PMID- 20359034 TI - Dehydropolymerization of 1,1-dihydrotetraphenylsilole and 1,1 dihydrotetraphenylgermole to optoelectronic copolymers catalyzed by colloidal silver nanoparticles. AB - The co-dehydrocoupling at ambient air atmosphere of 1,1-dihydrotetraphenylsilole 1 and 1,1-dihydrotetraphenylgermole 2 (9:1 mole ratio) with 2 mol% of AgNO3 in toluene at 90 degrees C produces optoelectronic poly(silole-co-germole)s 3 in high yield. The copolymer mainly has Si-Si bonds (and Si-Ge/Ge-Ge bonds in minor) along with the small portion of Si-O/Ge-O bonds in the polymer backbone chain. While Ag2SO4 is also a good catalyst as AgNO3 for the co-dehydrocoupling, AgI is a moderate catalyst. However, CP2Co, Cp2Ni, Cp2ZrCl2/Red-Al, AgX (X = F, Cl, Br) and AgI@MWCNT do not show appreciable catalytic activity. The silver complexes (AgNO3, Ag2SO4, AgI) transformed to colloidal silver nanoparticles during the catalytic reaction. The co-dehydrocoupling of 1 and 2 with AgNO3 even at dry nitrogen atmosphere is occurred, supporting that the oxidation of NO3- ion to NO2 is only the possible oxygen source, but not from the adventitious moisture in air. All cyclodextrins (sigma, beta, and gamma forms) considerably deteriorated the co-dehydrocoupling of 1 and 2 probably by forming toluene-insoluble inclusion complexes and by encapsulating SiH2 moiety. The resulting copolymer emits green light at 521 nm and is electroluminescent at 523 nm, which is similar to the polysilole. PMID- 20359035 TI - Morphology and vulcanizate properties of ethylene-propylene-diene rubber/ styrene butadiene rubber blends. AB - Morphology and vulcanizate properties of EPDM/SBR blends were investigated. AAHR (a mixture of aliphatic and aromatic hydrocarbon resins) was used as a compatibilizer and bis(3-triethoxysilylpropyl)tetrasulfide (TESPT) was used as a coupling agent. The vulcanizate properties and the morphological studies revealed that EPDM and SBR were incompatible, and the addition of AAHR was very effective to enhance the compatibility between EPDM and SBR. The weight percent of bound rubbers was increased with increasing SBR contents. The addition of an AAHR increased the amounts of bound rubbers, and hence the vulcanizate properties such as tear strength and fatigue resistance of the EPDM/SBR blends were improved. The dynamic mechanical analysis and the morphological studies revealed that the addition of TESPT increased the weight of bound rubbers and provided better dispersion of carbon black, resulting in good mechanical properties such as tear strength and fatigue resistance of the vulcanized EPDM/SBR blends. The smaller particle of zinc oxide (i.e., 50 nm > 100 nm > 1000 nm) yielded to the better blending properties of the polymer blend. PMID- 20359036 TI - What were you thinking? PMID- 20359037 TI - Dr. Jessica Guy: career and family takes multitasking to new levels. PMID- 20359038 TI - Dr. Drew Carlin: conquering new challenges every day. PMID- 20359039 TI - Dr. Stefanie S. Walker: going the extra mile for the next generation of dentists. PMID- 20359040 TI - Dr. Alejandro Montalvo: overcoming initial hardships builds confidence. PMID- 20359041 TI - Dr. Sara Haines: navigating the unique challenges of a dentist and new mom. PMID- 20359042 TI - Dr. Constance Wilson: practice thriving despite surprises, bumps in the road. PMID- 20359044 TI - Wait, late and rebate. PMID- 20359043 TI - Keeping current with the evolving makeup of the Pennsylvania population. AB - The changing residential population of the Pennsylvania requires continued monitoring if health practitioners are to maintain an awareness of the individuals in their community. A review of federal agency reports provides a general overview of Pennsylvania and national demographic and health factor characteristics. PMID- 20359045 TI - It's not just about the teeth. PMID- 20359046 TI - Take issue with MCDC article. PMID- 20359048 TI - The ethics of a doctor's due diligence. PMID- 20359047 TI - Smilematters. Patient fact sheet: "For a sparkling smile, remember to brush and floss everyday!". PMID- 20359049 TI - Illegal arrangements with dental laboratories. PMID- 20359050 TI - Is this really harassment? PMID- 20359051 TI - Can I stop a peer review complaint once it's started? PMID- 20359052 TI - Striking a balance between practice cash flow and personal spending. PMID- 20359053 TI - U-M study: people with less education could be more susceptible to flu. PMID- 20359054 TI - Submitting dental claims: tips for faster processing. PMID- 20359055 TI - What to do when a partnership goes sour. PMID- 20359056 TI - Start your career right by making good decisions. PMID- 20359057 TI - Is your practice at the "center" of a controversy? PMID- 20359059 TI - Unfortunate display. PMID- 20359058 TI - Firm footing. PMID- 20359060 TI - Where the candidate stands. PMID- 20359061 TI - A paradigm shift in dental education. How can we address the current challenges? PMID- 20359062 TI - Single-tooth zirconia implant located in anterior maxilla. A clinical report. AB - Expectations regarding esthetics in dentistry are growing and research in the field of all ceramic materials for restoration of natural dentition and dental implants has intensified. Although the crown that covers the abutment of an implant may be esthetically optimal, the possibility exists that the grayish color of the titanium implant shines through the thin peri-implant mucosa and, because of the short peri-implant tissue recessions, impairs the entire esthetic result. To improve the esthetic aspect of dental implants, a ceramic material, zirconia, was introduced. We present a case in which a zirconia implant and an all-ceramic crown system were used for the maxillary anterior region and followed for 12 months. PMID- 20359063 TI - Oral mucositis. Review of literature. AB - The standard treatment for malignant neoplasia of the cervicofacial area is surgery in association with radio- and/or chemotherapy. These therapies can cause local and systemic complications. Mucositis is the most common dose-correlated complication to the oral cavity. It is particularly difficult to treat in patients who are already physically and psychologically exhausted by the tumoral pathology. This study illustrates, through a review of the literature, the attack rate, the pathogenesis and the clinical course of the mucositis, as well as the correct dental approach and clinical-therapeutic management of these patients, with the aim of improving the quality of their lives. PMID- 20359064 TI - Bone remodeling and individual-based implant therapy. AB - There has been a strong movement in implant dentistry to immediately load implants at time of placement. This movement has been generated by implant manufacturers, who have acceded to patient wishes for faster function and fewer surgeries. Immediate function has been a therapy for tooth extraction and implant replacement and for implant loading at the time of implant placement in edentulous sites. Bone is a dynamic connective tissue and its reaction to surgery is in response to modeling and remodeling. In this paper, the literature of bone remodeling is reviewed, with emphasis on various parameters that modulate this process and have an impact on the healing period of osseointegration and the prognosis for immediate or delayed loading of dental implants. These parameters define a bone phenotype characteristic of each individual. I suggest a new therapeutic concept for implant dentistry that I call "individualized implant therapy". PMID- 20359065 TI - Surreptitious surgery on Long Island Sound: The oral cancer surgeries of President Grover Cleveland. AB - Grover Cleveland rose from being the mayor of Buffalo to the governor of New York to the president of the United States. At the start of Cleveland's second term as president, the nation was involved in a severe financial crisis, the extent of which was not known by the general public. President Cleveland was to make a strong appeal to Congress in the coming months to repeal the Sherman Silver Purchase Act of 1890. He thought this would set the nation on the road to fiscal recovery. However, his vice president, Adlai Stevenson, strongly opposed repeal of the Sherman Act. Prior to scheduling his appearance before Congress, President Cleveland noticed a rough spot on his palate. A biopsy confirmed that it was cancer, and it was determined that surgery was needed. Cleveland and his advisors thought the nation would be thrown into a panic if the President's health did not remain a secret. A surgical team, which included a dentist, performed the surgery in secrecy while traveling aboard a yacht. A prosthetic obturator was fabricated by a New York prosthodontist to close the surgical defect. Cleveland recovered well, made a forceful speech before Congress, had the Sherman Act repealed and lived without a recurrence of his oral cancer for the rest of his life. The public remained unaware, for the most part, of the gravity of President Cleveland's health for decades. PMID- 20359066 TI - Joint sounds in complete denture wearers. Literature review. AB - Long-term denture wearers can present with prosthesis instability, reduced occlusal vertical dimension and incorrect positioning of the jaw. This can lead to muscular changes and joint vibration. This study presents the main considerations related to joint vibrations in partially or totally edentulous patients. Occlusal treatment improves the disc-condyle relationship in the mandibular fossa. Furthermore, a detailed clinical exam and anamnesis must be performed to identify the dysfunction and its etiology, so that appropriate treatment can be provided. PMID- 20359067 TI - Increasing population, limited dental insurance, but increasing use of services. AB - During the careers of many current and soon-to-be dental practitioners, one-in five residents of the U.S. will be 65-plus years of age. Although the current population of seniors has limited dental insurance coverage, older Americans are increasing their use of services. Demographic variations are reviewed in terms of the need for services, dental visit patterns and expenditures for services. A challenge is presented to prepare practitioners for the care of this burgeoning population. PMID- 20359068 TI - The question for universities: how can they win the war on attrition? PMID- 20359069 TI - Tempting treats. AB - In the third article in our series on managing change, Dorothy Jeffery describes how she improved nutrition in long-term care. PMID- 20359070 TI - Bosom buddies. AB - Exclusive breastfeeding for the first six months gives babies the best possible start in life, but only 2 per cent of UK women achieve this goal. PMID- 20359071 TI - Meeting changing needs. AB - The Terrence Higgins Trust has been at the forefront of offering care and support since the beginning of the HIV/AIDS epidemic. PMID- 20359072 TI - Who's smiling? PMID- 20359073 TI - Medicines management. PMID- 20359074 TI - Measuring the safety climate in NHS organisations. AB - This article discusses the differences between organisational culture and organisational climate, and provides an overview of the relationship between safety culture and safety climate within these wider concepts. The article concludes with a brief description of an initiative to test a safety climate measurement tool for use in NHS organisations. PMID- 20359075 TI - Caring for patients with long-term conditions and depression. AB - Long-term conditions are an increasingly important part of healthcare activity. The prevalence of these health problems is high and their personal and social effects are extensive, requiring an approach to health care that emphasises integration, continuity and self-care. The risk of depression is significantly increased among people with chronic illnesses. Recognising and assisting in the management of this aspect of care is a crucial part of the nurse's role. To help people with long-term conditions, services need to be organised so that the assessment and recall of all patients at risk is co-ordinated, and to ensure a range of treatments, including case management, is available for those who are depressed. Nurses need to be familiar with appropriate case-finding tools, and to have knowledge of and access to evidence-based treatments ranging from guided self-help and exercise, to problem-solving, antidepressant and cognitive therapies. PMID- 20359076 TI - Wound care and pain assessment. PMID- 20359077 TI - Managing acute skin reactions to radiotherapy treatment. AB - Promoting tissue viability and caring for skin damaged as a result of radiotherapy are critical to the quality of care patients receive. However, few nurses recognise fully the effect of radiotherapy on tissue viability and wound healing. This article considers the causes and types of skin damage resulting from radiotherapy treatment that nurses may encounter, and how this damage can be graded. Based on the extent of skin reaction to radiotherapy, management options are explored, illustrated by a case study. A guide to product selection, derived from the authors' experience, is presented. PMID- 20359078 TI - Implementing the quality accounts agenda in tissue viability. AB - This article attempts to summarise and interpret recent quality initiatives from the Department of Health to improve tissue viability nursing services across England. It is directed towards nurses responsible for the planning and delivery of tissue viability services, and to nursing management at trust level. Quality initiatives are aimed at encouraging trust board members and service providers to assess, and make public, the quality and standards of care that they provide in the form of quality accounts. All healthcare service providers will have to produce a quality account in 2010. This article offers guidance on the use of quality indicators or nursing metrics to measure quality, and prepare quality accounts in tissue viability. PMID- 20359079 TI - Pathway for learning. PMID- 20359080 TI - Sorting out home delivery. PMID- 20359081 TI - Easing the step up from junior roles to taking charge of a unit. PMID- 20359082 TI - Essential care. PMID- 20359083 TI - [Polymorphisms of GSTM1, GSTT1 and susceptibility of laryngeal and hypopharyngeal carcinomas]. AB - OBJECTIVE: To study the relationship between genetic polymorphisms of GSTM1 GSTT1 and the susceptibility of laryngeal and hypopharyngeal carcinomas (LHC). METHOD: The GSTM1 and GSTT1 genotypes were determined by multiplex PCR analysis in 76 LHC patients and 76 population controls. The association between the genotypes and LHC risk was measured by odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULT: The frequency of GSTM1 null genotype was 59.2% in the LHC patients and 42.1% in controls (OR=1.935, 95% CI=1.069-3.510), the difference was significant (P<0.01). The frequency of GSTT1 null genotype was 57.9% in the LHC patients and 51.3% in controls. The difference was not significant (P>0.05). In smokers, the risk of the LHC increased in subjects of GSTM1 null genotype (OR=5.545, 95% CI=2.158-13.528). CONCLUSION: GSTM1 polymorphisms are associated with susceptibility to the LHC. It has the synergistic effects with smoking in the development of the LHC. GSTT1 genotypes might have no association with risk of the LHC in urban Linyi. PMID- 20359084 TI - [Study and analysis on the quantitive detection of EBV-DNA in adenoidal hypertrophic and tonsillitis tissues of children]. AB - OBJECTIVE: To investigate the epidemiology of EBV in adenoidal hypertrophy and chronic tonsillitis and discuss the affection of EBV on the nosogenesis of adenoidal hypertrophy and tonsillitis of children. METHOD: Fifty-two children with chronic tonsillitis and/or adenoidal hypertrophy had the operations of the tonsillectomy and/or the adenoidectomy. These tissues resected and plasma of all cases were detected to find EBV-DNA by RQ PCR. RESULT: The infection rate of EBV in the tissues of adenoidal hypertrophy and tonsillitis of children was 51.9%. The boys' infection rate of EBV was 50.0%, and the girls' infection rate of EBV was 55.6%, which had not significantly different. The EBV infection rate in the tissues of tonsillitis was 40.4%, The EBV infection rate in the tissues of adenoidal hypertrophy was 48.9%, which had not significant difference. The school age group (7- to 14-years-old) presented higher infection rate of EBV in the tissues of adenoid and tonsil (65.5%) than the pre-school children group (2- to 6 years-old) (34.8%). Comparing the copies numbers of EBV-DNA in the different degrees of adenoidal hypertrophy, we found that the copies numbers of EBV-DNA in the severe hypertrophy group were higher than the midrange and slight hypertrophy groups (P<0.05). Meanwhile we detected EBV-DNA in these childrens' blood plasma by RQ-PCR. No blood plasma was detected EBV-DNA copies higher than normal (< 1 x 10(3) copies/ml). CONCLUSION: The tissues of adenoidal hypertrophy and tonsillitis had same sensitivity to EBV. There was not significant difference between the infection rates of the boys and girls with adenoidal hypertrophy and/or tonsillitis. With these children growing up and the course of diseases prolonging, the infection rate of EBV increased correspondingly. There was a certain correlation between the hypertrophy of adenoid and EBV. There were no EBV DNA fragments in blood plasma of the children with adenoidal hypertrophy and/or tonsillitis. So there were essential different between benign hyperplasia and nasopharyngeal carcinoma. PMID- 20359085 TI - [The expression and significance of Pin1 and CyclinD1 in adult papilloma of larynx]. AB - OBJECTIVE: To study the expression and relationship of Pin1 and CyclinD1 in adult papilloma of larynx, and the effect of both in laryngeal papilloma's canceration. METHOD: Ninety-two cases of paraffin section with immunoperoxidase (SP) staining method was used to detect the distribution of Pin1 and CyclinD1 in 10 cases of laryngeal normal epithelial tissue, 39 cases of laryngeal papilloma, 27 cases of laryngeal papilloma with middle, severe atypical hyperplasia and 16 cases of laryngeal carcinoma. RESULT: The distribution of Pin1 and CyclinD1 increased gradually from laryngeal normal epithelial tissue to laryngeal carcinoma (P<0.05); No difference of the expression of CyclinD1 (not including Pin1, for Pin1, P=0.009) was found between laryngeal papilloma and laryngeal papilloma with middle, severe atypical hyperplasia (P>0.0125), but there had significant difference of the expression of Pin1 and CyclinD1 among the rest groups; There was significantly direct correlation between the expression of Pin1 and CyclinD1 (P<0.05). CONCLUSION: The hyper-expressions of Pin1 and CyclinD1 may play a key role in laryngeal papilloma's malignant change. Pin1 up-regulating the expressions of cyclinD1 possibly participate in its malignant change. PMID- 20359086 TI - [Analysis of proteomic spectra in serum from patients with laryngeal carcinoma by SELDI-TOF-MS technology]. AB - OBJECTIVE: To screen the tumor markers of laryngeal carcinoma and to investigate their expression in preoperative and postoperative serum. METHOD: The distinct protein in serum was detected in 32 cases of laryngeal carcinoma and 38 healthy people by IMAC-Cu proteinchip array and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The distinct proteins in serum were detected in 32 cases of laryngeal carcinoma preoperation and within 10 days 15 cases of laryngeal carcinoma postoperation with the same methods. The discriminatory profiling between preoperative and postoperative patients was analyzed by Biomarker Wizard software and Biomarker Pattern software. RESULT: The results showed that fifteen differentially expressed proteins in serum were screened by analysis of proteomic spectra of preoperative patients and normal subjects. Seventeen kinds of protein differentially expressed in serum were screened by analysis of proteomic spectra of preoperative and postoperative patients. Six kinds of protein (2958.52, 3796.89, 5148.86, 6115.57, 4052.18, and 7770.76) were obtained for making up patterns that was able to class the preoperative-team and postoperative-team. Corresponding correct ratio were 84.38% (27/32) and 73.33% (11/15). CONCLUSION: The preliminary results suggest that classification system will provide a highly accurate and innovative approach for the early diagnosis of laryngeal carcinoma and judgement of prognosis. SELDI-TOF-MS technology is a useful tool for a high throughput screening of large-sized serum samples to discover potential biomarkers for laryngeal carcinoma. PMID- 20359087 TI - [The relationship between the abnormal behavior and serum C-reactive protein in children with obstructive sleep apnea-hypopnea syndrome]. AB - OBJECTIVE: To explore the pathogenesis of abnormal behavior in children with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: The behavioral problems and C-reactive protein were measured in 40 children with OSAHS and 30 children with habitual snoring who underwent overnight Polysomnography, 40 cases of healthy children for the control group. RESULT: The ratio of abnormal behavior in OSAHS and habitual snoring children was significantly higher than that of the healthy control group, while no significant difference between the two groups. The content of C-reactive protein in OSAHS children (4.24 mg/L) was significantly higher than habitual snoring (2.76 mg/L) and healthy control group (1.27 mg/L); in habitual snoring children C-reactive protein was higher than in healthy control group. The content of serum C-reactive protein in OSAHS children accompanied by abnormal behavior (4.63 mg/L) was significantly higher than that without abnormal behavior (3.23 mg/L). The content of serum C-reactive protein content in habitual snoring children accompanied by abnormal behavior (3.63 mg/L) was significantly higher than that without abnormal behavior (1.76 mg/L). CONCLUSION: OSAHS and habitual snoring children have more behavior problems. C reactive protein levels are higher in children with OSAHS and habitual snoring, and the levels of C-reactive protein are related to the abnormal behavior in these children. PMID- 20359088 TI - [Difference of upper airway variety with respiration in the sufferer of OSAHS and normal adult]. AB - OBJECTIVE: To inquiry the variety difference of upper airway caliber OSAHS sufferer and normal person in quiet respiration. METHOD: Twenty OSAHS sufferer who were viewed by PSG and 16 normal adults who hagve no chief complaint of sleeping disease were selected. The curves of the subjects in a respiratory cycle were recorded by respiratory monitoring system in PSG, while the morphological changes in the pharynx of all subjects were observed by fiberscope in a calm respiratory cycle, and then both of the two processes simultaneously were recorded on the same computer. According to the different stages of respiratory cycle by analyzing respiratory curve the video had been edited into pictures about the various anatomical areas in the upper airway, the cross section area and the dimension of palate and lingua and root of the tongue region upper airway whereas studied by the image tools in computer, and the changes of areas and dimensions at palate, and lingua and root of the tongue region upper airway were calculated. RESULT: It was found that there wasps a morphological change of the upper airway with the respiratory movement in the both groups. The upper airway caliber decrease with inspiration begin and reach the most narrowing at the end of inspiration, then upper airway caliber enlarges with the expiration begin and reach the most widening at the end of expiration. No matter the normal group or the OSAHS group has the obvious changes in the palate and lingua region on the diameter, the cross section area and the dimension in respiration. The changes in the palate and lingua region on the diameter, the cross section area and the dimension of OSAHS group were greater than normal group. No matter OSAHS group or normal group on the diameter and cross section area change in the palate was obviously more than the tongue area and the root of tongue area. The changes of OSAHS group on the dimension in the palate were greater than the tongue area and the root of tongue area. CONCLUSION: There are periodically changes of upper airway during respiration cycle in normal adults and OSAHS patients. The effects of respiration on upper airway caliber of OSAHS patients are more obviously than normal adults, and the increasing effects in OSAHS patients is one of OSAHS etiology. PMID- 20359089 TI - [The expression of oncogene c-myc and its role on human laryngeal cancer]. AB - OBJECTIVE: To detect the expression of oncogene c-myc and explore its role on human laryngeal cancer. METHOD: The mRNA and of oncogene c-myc levels were detected in human laryngeal cancer tissues and laryngeal normal tissues by the means of real-time PCR and immunohistochemistry, respectively. RESULT: Compared with normal laryngeal tissues, the mRNA and protein levels of oncogene c-myc were both upregulated in laryngeal cancer tissues of all differentiation degree (P<0.05). Moreover, the level of c-myc was inverse correlated with the differentiation degree in human laryngeal cancer tissues. CONCLUSION: The oncogene c-myc is overexpressed in human laryngeal cancer tissues, and c-myc may play an important role in carcinogenesis and progression of human laryngeal cancer tissues. It may provide a new target for gene therapy of human laryngeal cancer. PMID- 20359090 TI - [Expression and pathobiological significance of Col I, Col IV and Fn in laryngeal squamous cell carcinomas]. AB - OBJECTIVE: To investigate the expression of collagen type I (Col I), collagen type IV (Col IV) and fibronectin (Fn) in laryngeal squamous cell carcinomas (LSCC) and their pathobiological relationship with invasion and metastasis of tumor. METHOD: The expression of Col I, Col IV and Fn was detected by immunohistochemistry method in normal tissue of latero-carcinoma and tissue of carcinoma in 60 specimens of LSCC. Integral optical density (iOD) was detected by image analysis of computer and was analyzed by SPSS13.0. RESULT: The expression of Col I was obvious and integrity. The expression of Col IV and Fn of basal membrane was like intact line-shape appearance and Fn of interstitial substance appeared like a complete network in the normal tissue of latero-carcinoma. Their expression decreased gradually and their integrity was broken and disappeared gradually from well to poorly differentiated LSCC. Their expressions also fell off with the tumor size, clinical stage and cervical lymphatic metastasis gradually and consistently in LSCC. Their variances were statistical significance separately (P<0.05 or P<0.01). CONCLUSION: The expression of Col I, Col IV and Fn was closely related to tumor invasion, the regional lymph node metastasis and other some pathobiological features in LSCC. A detection of Col I, Col IV and Fn was of definite significance on a better comprehension of the possibility of metastasis, choice of surgery and prognosis. PMID- 20359091 TI - [Comparing MSCT with MRI in preoperative staging of laryngeal carcinoma]. AB - OBJECTIVE: To investigate the value of MRI and MSCT in TNM staging of laryngocarcinoma. METHOD: Thirty-seven patients with laryngocarcinoma were underwent by contrast enhanced scan and multiplanar reconstruction. Thirty-five patients with laryngocarcinoma were underwent contrast enhanced multislice spiral CT, which of them were done by MPR. There are 28 cases which were scan by MRI and MSCT in the two former and we contrasted the accuracy rating in laryngeal manifestation of abnormality. In the former two groups, we observed them the variability in the aspect of lymphaden metastasis and TNM staging. RESULT: In all 28 cases, the MRI had better accuracy rating in displaying the parts of preepiglottic space, larynx side interspace, lingual root, neck tissue, vocal cord. In the TNM staging, there was no difference in stage one in accuracy rating, as the stag stepping up, the accuracy rating of MRI had became better. The last result was that the two methods had difference in staging. In the two methods, MSCT had better sensitivity, specificity and accuracy rating. CONCLUSION: MRI and MSCT had good accuracy rating in TNM staging, MRI has better accuracy rating in some of laryngeal, but as the lymphaden metastasis, the MSCT was better. There were variability in staging, and the MRI was better. PMID- 20359092 TI - [Study of the effect of JNK signal transduction pathway in intense noise-induced apoptosis in cochlea of guinea pig]. AB - OBJECTIVE: To investigate the mechanism of intense noise-induced cochlea cells death in guinea pig, and the effect of JNK signal transduction pathway in the procedure of cochlea cells apoptosis by intense noise-induced. METHOD: Thirty-two guinea pigs were randomly divided into 4 groups. The guinea pigs in the experiment groups were exposed to 4 kHz narrow band noise at 120 dB SPL for 4 h. After the noise expose for 1, 4, 14 days of the experiment guinea pigs, ABR of the guinea pigs on experiment and control groups were tested before put them to death. Four guinea pig's cochleas of every group were taken to paraffin section, and the rest was extracted the total cochlear's protein. Apoptosis was tested by terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyuridine triphosphate (d UTP) nick and labeling method (TUNEL). The phosphorylation of JNK and c-Jun were tested by immunohistochemistry and western blot methods. RESULT: Tunel-Positive cells in the Corti's, SGC and SV of experiment groups, and there have significant differences compared with the control group (P<0.01) and Tunel-Positive cells are most in 1 d experiment group. The positive cells of P-JNK and P-c-Jun could be detected in guinea pig's cochleas after noise exposed, but no positive cells were found in the control. Protein levels of P-JNK and P-c-Jun were risen up and activated quickly after noise exposed, and achieved peak in 1 d, 4 d and then fallen-offs, but still maintained higher levels within 14 d. CONCLUSION: Intense noise causes cochlea cell lesion by inducing apoptosis to result in and JNK signal transduction pathway plays an important role in the procedure of apoptosis. PMID- 20359093 TI - [The diagnostic value of high resolution CT in assessment of temporal bone traumatic facial nerve paralysis]. AB - OBJECTIVE: To investigate the diagnostic value of high resolution CT for temporal bone traumatic facial nerve paralysis and the guidance significance for surgery. METHOD: Twenty-nine patients of traumatic facial nerve paralysis were investigated. The predictive diagnosis was made according to the clinical data and the image features of HRCT, then a comparative analysis of the preoperative image features and the surgical findings were carried out. RESULT: The trend of temporal bone fracture displayed on the CT scan was basically consisted with the surgical findings. The direct CT signs of facial nerve injury include the bone fracture line went through the tube, bone tube rupture or continuity interruption, while the indirect CT signs include local incrassation of the facial nerve, lower bone density of the tube, geniculate fossa expansion, oppressed facial nerve, et al. The predictive diagnostic accordance rates of all the image features were above 90% as to the surgical findings. CONCLUSION: High resolution CT could localize the trend of temporal bone fracture,and is helpful to estimate the extent of facial nerve injury and other complications. High resolution CT could provide reliable basis for clinical diagnosis and treatment. PMID- 20359094 TI - [Analysis of imaging and clinical feature of leukoencephalopathy with hearing loss first complaint]. AB - OBJECTIVE: To investigate the imaging and clinical feature of leukoencephalopathy with hearing loss first complaint. METHOD: The head MRI and clinical feature of 7 cases leukoencephalopathy with hearing loss first complaint were retrospectively analysed, including their place, shape, range and blood plasma very-long-chain fatty acid (VLCFA). RESULT: The head MRI of 2 cases shows symmetry distributed long T, and T2 signal like butterfly aliform in white matter beside both cornu posterior ventriculi lateralis. The head MRI of 5 cases shows abnormal long T1 and T2 signal in different part in Alba. The pathological changes often located in white matter of frontal lobe and secondly beside both cornu posterior ventriculi lateralis. The shape shows little patching in 7 cases. The range only shows beside cornu posterior ventriculi lateralis in 2 cases. The range only shows in frontal lobe in 1 cases. Two or more than two parts shows in the rest 5 cases. The result of VLCFA is normal in 3 cases. The rest 4 cases refused to have examination of VLCFA. CONCLUSION: The patient who firstly complained of hearing loss should be routinely done head MRI. The head MRI imaging could clearly show abnormal white matter in order to avoid omitting existent pathological changes. PMID- 20359095 TI - [Implication of technique of "two-flap" in ear reconstruction]. AB - OBJECTIVE: To explore the technique of "two-flap" in ear reconstruction. METHOD: Quantitative tissue expansions were used in the mastoid area in the first stage. After the final injection, there was 1 month of sustaining time. Expanded skin flap and unexpanded fascia flap were designed in the second stage, so the "two flap" technique was used in the ear reconstruction. From January 2004 to December 2008, 1427 patients of microtia were treated using "two-flap" technique. RESULT: The expanded skin flap could show the fine structures of the reconstructed ears. The reconstructed ears had vivid cranioauricular angle after using the unexpanded fascia flap. CONCLUSION: "Two-flap" method was easily manipulated and the complications were rare. The reconstructed ears had lucid and three-dimensional contour. PMID- 20359096 TI - [Long-term results of endolymphatic sac decompression and endolymphatic-mastoid shunting for Meniere's disease]. AB - OBJECTIVE: To investigate the efficacy of endolymphatic sac surgery for Meniere's disease, and compare the effects of endolymphatic sac decompression with endolymphatic-mastoid shunting. METHOD: Twelve patients(13 ears) undergoing endolymphatic-mastoid shunting and eleven patients (11 ears) undergoing endolymphatic sac decompression were retrospectively compared for hearing results and vertigo controlled rates. All of them have been followed up for more than two years after surgery. RESULT: According to Chinese Meniere's disease diagnosis and curative effect standard evaluation criteria published in 2006, for vertigo symptom of endolymphatic mastoid shunting group, 9 cases (69.2%) achieved grade A(completely controlled), 4 cases (30.8%) achieved grade B (fundamentally controlled). There were 8 cases (72.7%) with grade A, 2 cases (18.2%) with grade B and one case (9%) with grade C among 11 patients who received endolymphatic sac decompression. There was not statistically significant differences in postoperative speech pure tone average and vertigo controlled rate between the two groups. CONCLUSION: Endolymphatic sac decompression and endolymphatic-mastoid shunting are effective management with less complication for intractable Meniere's disease. Particularly, the vertigo symptoms were controlled significantly. Patients with Meniere's disease in advanced clinical stages may also be relieved. PMID- 20359097 TI - [Analysis of evoked otoacoustic emission in normal pure tone hearing thresholds patients with aural fullness]. AB - OBJECTIVE: To analyze normal pure tone hearing thresholds patients with aural fullness using evoked otoacoustic emission in order to detect the early cochlear impairment. METHOD: Forty-three normal pure tone hearing thresholds patients (72 ears, aural fullness group) with aural fullness were served as subjects and 30 normal volunteers (60 ears, control group) as controls. Transiently evoked otoacoustic emission (TEQAF) and distortion product evoked otoacoustic emission (DPOAE) were tested with Capella otoacoustic emission machine. The DPOAE detection rate and amplitudes at all frequencies,the passing rate and wave signal noise ratio (SNR) ,wave reproducibility, band SNR and band reproducibility of TEOAE were recorded and analyzed. RESULT: (1) Only on the frequency points of 0.50 kHz and 0.75 kHz, the detection rate of DPOAE in aural fullness group was lower than that in control group (P < 0.05). There was no significant difference in the rate among other frequency points (P > 0.05). (2) The passing rate of TEOAE was 100w in control group and 90. in aural fullness group. There were statistical differences between two groups (chi2 = 6.16, P < 0.05). (3) Compared with the control group, the DPOAE amplitudes at all frequencies, the wave signal noise ratio (SNR), wave reproducibility, band SNR and band reproducibility of TEOAE in patients with aural fullness were significantly decreased. There were statistical differences (P < 0.05 or P < 0.01). CONCLUSION: Some patients of normal hearing thresholds with aural fullness have had early harm of Outer hair cell in cochlear. TEOAE and DPOAE may he used to detect these lesions early before the hearing impairment occurred. PMID- 20359098 TI - [Retaining time of tympanic ventilation tube and aural complications]. AB - OBJECTIVE: To study the relationship of retaining time of tympanic ventilation tube and aural complications. METHOD: Three-hundred-five patients(659 ears)with otitis media with effusion (OME) received tympanostomy tube insertion. The tube were removed 6-36 months after tube insertion. Then aural complications were recorded in different tube retaining time, followed with a statistic analysis. RESULT: Fifty-five tubes of 29 patients were removed at 1-6 months after tube insertion, with spontaneous extrusion 3.4%, blocked tube 10.3%, intrusion into the middle ear 0, granulation tissue 0, cholesteatoma 0, otorrhea 6.9%, perforation 0. One hundred and ninety tubes of 96 patients were removed at 6-12 months after tube insertion , with spontaneous extrusion 7.3%, blocked tube 15.6%, intrusion into the middle ear 1%, granulation tissue 0, cholesteatoma 0, otorrhea 5.2%, perforation 0. Three hundred and eight tubes of 156 patients were removed at 12-24 months after tube insertion, with spontaneous extrusion 9%, blocked tube 12.8%, intrusion into the middle ear 1.3%, granulation tissue 1. 9%, cholesteatoma 0.6%, otorrhea 2.5%, perforation was 0. One hundred and sixty one tubes of 83 patients were removed at 24-36 months after tube insertion, with spontaneous extrusion 36.1%, blocked tube 53%, intrusion into the middle ear 6%, granulation tissue 3.6%, cholesteatoma 2.4%, otorrhea 2.4%, perforation 2.4%. CONCLUSION: The occurrence of complication didn't increase with time going by when the ventilation tube retained less than two years. However, when the ventilation tube retained more than two years, the occurrence of spontaneous extrusion and blocked tube increased obviously. PMID- 20359099 TI - [Analysis of prognosis factors of idiopathic sudden hearing loss]. AB - OBJECTIVE: To study the prognosis factors of idiopathic sudden hearing loss. METHOD: The clinical data of 165 patients with idiopathic sudden hearing loss were retrospectively studied and the computer software was used to investigate the relevant effects on prognosis. RESULT: The prognosis of patients who had been treated within 14 days under the age of 55 were better. The prognosis of the elderly and the patients with vertigo and high hearing loss were not satisfied. Sex, tinnitus, cardiac or cerebral vascular diseases, diabetic and the medicine or the duration of treatment have no statistical points on prognosis. CONCLUSION: The prognosis of idiopathic sudden hearing loss related with the treatment time and coverage and extent of the damaged inner ear. PMID- 20359100 TI - [Analysis of deafness gene mutations by gene chip and its clinical significance]. AB - OBJECTIVE: To analyze deafness gene mutations by genechip. METHOD: The peripheral blood samples were obtained and DNA templates were extracted by extraction kits. The deafness gene mutations were distinguished by genechip. RESULT: Among 42 patients with non-syndromic hearing loss, GJB2 235delC was found in 11 cases (7 cases were homozygosis, 4 cases were heterozygosis); 4 cases were shown to carry the PDS IVS7-2A>G mutation. CONCLUSION: The incidence of GJB2 gene and PDS IVS7 2A>G mutations among the deaf- mute children in Guiyang city is 38.10%. Molecular genetic screening for these mutations and genetic counseling are effective methods to prevent the occurrence of hereditary hearing loss. PMID- 20359101 TI - [The prevalence of otitis media with effusion of kindergarten children in Wuhan city]. AB - OBJECTIVE: To investigate the prevalence of otitis media with effusion (OME) of kindergarten children in Wuhan City. METHOD: The study subjects were 3-6-year-old children in some kindergarten children in Wuhan City . All subjects were assessed with routine otorhinolaryngologic examination, otoscopic examination and tympanometry. Chi-square test were used to analyse the difference of data. RESULT: The prevalence of children of some kindergarten in Wuhan City is 6.67%. There was no statistical difference were found between sexuality. The prevalence of OME in 3 years old group is obviously higher than that in 4-6 years old group. Previous acute otitis media episodes, feeding, high-arched palate, and nasal obstruction are risk factors of OME. CONCLUSION: Children with previous acute otitis media episode and nasal obstruction should be suggested to have otorhinolaryngologic examination regularly. It is necessary to have routine otoscopic examination and tympanometry in children of kindergarten. PMID- 20359102 TI - [Electrophysiologic study of murine spiral ganglion neurons]. AB - OBJECTIVE: To explore the nature of voltage dependent ion channels and basic electrophysiological characteristics of cochlear spiral ganglion neurons of apical and basal turn by patch clamp techniques of whole cell configure on murine spiral ganglion neurons. METHOD: Different voltage dependent ionic currents were recorded with patch clamp techniques of whole cell configure on the condition of different internal electrode solution, blockers and stimulus protocol. RESULT: Inward sodium channel current (I(Na)), hyperpolarization-activated inward cationic current (Ih), outward delay rectification potassium current (I(K)) and outward transient potassium current (I(A)) were recorded ,significant difference of electrophysiological characteristics of I(A) and I(K) was found between apical and basal turns (P < 0.05). CONCLUSION: Various ionic currents are recorded, which shows that spiral ganglion neurons have the base of ionic channels to complete formation,conduction and modulation of action potential for auditory information transduction, the difference of electrophysiological characteristics between apical and basal turns contributes to the course of hearing formation. PMID- 20359103 TI - [Expression of toll-like receptors signaling pathway in chronic rhinosinusitis with nasal polyps]. AB - OBJECTIVE: To investigate the expression of Toll-like receptors (TLRs) signaling pathway in chronic rhinosinusitis (CRS) with nasal polyps. METHOD: Gene microarray analysis was used to detect the expression of TLRs signaling pathway in CRS with nasal polyps. RESULT: Of 19 differentially expressed (two fold changes), 4 genes were upregulated and 15 genes were downregulated. CONCLUSION: The differentially expressed genes in TLRs signaling pathway may exert its effect in the pathogenesis of CRS. In addition, the roles of TLR9 and its agonists need further study. PMID- 20359104 TI - [Expression of CD23 and CD19 on peripheral blood lymphocytes and its association with serum total IgE in patients with allergic rhinitis]. AB - OBJECTIVE: To explore the expression of CD23, CD19 on peripheral blood lymphocytes as well as its association with serum total IgE levels and nasal allergic symptoms in patients with allergic rhinitis (AR). METHOD: Symptom scores were evaluated in 46 AR patients, expression of CD23, CD19 on peripheral blood lymphocytes were measured by flow cytometry, and serum total IgE levels were determined by immune chemiluminescence. Thirty two healthy individuals were enrolled as controls. RESULT: The percentage of CD23+, CD19+ and CD23+/ CD19+,on peripheral blood lymphocytes in AR patients were 11.6 +/- 1. , 22.8 +/- 3.3,10.2 +/- 1.7, respectively. Higher frequencies of CD23+, CD19+, and CD23+/CD19+ were found in AR patients compared with controls (P < 0.05). There were positive correlations between expression rates of CD23+, CD19+, CD23+/CD19+ and levels of serum total IgE, nasal allergic symptom scores, respectively. CD23+/CD19+ demonstrated greater correlations with serum total IgE and nasal allergic symptom (r = 0.65 and 0.49, P < 0.05) than CD23+ and CD19+ did. Correlation between CD23+/CD19+ and nasal allergic symptom scores was greater than the corresponding correlations of serum total IgE (r = 0.33, P < 0.05). CONCLUSION: CD23 and CD19 are important factors that associated with serum total IgE in the pathogenesis of AR, Analysis on the expression of CD23+/CD19+ on peripheral blood lymphocytes is helpful for evaluating the severity of AR. PMID- 20359105 TI - [Improvement on primary culture of human nasal epithelium by enzymatical dissociation]. AB - OBJECTIVE: To highlight the key points of primary culture of human nasal epithelial cells by enzymatical dissociation for high achievement ratio, and to establish a successful primary culture model for subsequent experiments. METHOD: Primary culture of human nasal epithelial cells was performed with enzymatical dissociation of isolated tissue in serum--free medium. On the basis of this method, some improvements were subjected, such as stripping mucosal epithelium from adjacent connective tissue, applying DNase type I to digesting procedure, adding trypsin directly to the collagenase solution containing digested mucosa pieces, employing uncoated culture dishes and so on. Immunofluorescence with a monoclonal anti-cytokeratin antibody 8/18 was used to confirm the epithelial nature of the cultured cells. RESULT: Nasal epithelial cells grew well and confluence on the 6th to 8th day. Positive expression of cytokeratin (CK) 8/18 showed the epithelial property of cultured cells. CONCLUSION: Primary culture model of human nasal epithelial cells can be successfully established by enzymatical dissociation. Improvements on processes of material using and enzyme digestion can gain a high achievement ratio and harvest a high purity and certain amount of reliable primary epithelial cells. PMID- 20359106 TI - [Non-distinctive features on CT scan of fungal sinusitis]. AB - OBJECTIVE: This article was a retrospective analysis on the preoperative CT scan of fungal sinusitis patients. The non-distinctive clinic feature was suggested to improve the accuracy of preoperative diagnosis. METHOD: A retrospective analysis was made for 176 patients with fungal sinusitis,which were confirmed by postoperative pathologic diagnosis from January 2000 to January 2008. Every patient was performed both CT examination and nasal endoscopy preoperatively. All patients underwent endoscopic sinus surgery and the lesions in sinus were cleared and confirmed fungal infection by pathology. Thirty-five cases fungal infection located in sphenoid sinus, 84 cases in maxillary sinus, 49 cases in both maxillary and ethmoid sinus, 3 cases in all sinus, 5 cases in both ethmoid and sphenoid sinus. There were 179 sinuses in 176 patients were infected. RESULT: This group totally had 175 cases (179 sides). One hundred and seventy-three cases had unilateral lesion,3 cases had bilateral lesion. The CT scan showed non distinctive features including uniform dense, uneven dense in the sinus and bone resorption of the inner side bone wall. Five cases in sphenoid sinus lesion were found calcification in CT scan but 8 cases didn't show such features. Among these cases, 5 cases showed uniform dense and 3 cases showed uneven dense. In 84 cases maxillary sinus lesion, there were 12 cases without distinctive change, among these cases,8 cases showed uniform dense, 4 cases showed uneven dense and 5 cases had bone resorption. In 49 cases both ethmoid and maxillary sinus lesion, 13 cases didn't show distinctive change, among these cases, 9 cases showed uniform dense, 4 cases showed uneven dense and 6 cases had bone resorption. Five cases had calcification in the both sphenoid and ethmoid sinus. Totally 81.56% of these patients had calcification feature in the CT scan. CONCLUSION: The calcification in the lesion of sinus is usually featured as characteristic manifestation of fungal sinusitis. But in clinic, the calcification does not exit in some patients CT scan. When being absent of the featured sign in CT scan, the fungal sinusitis have to be diagnosed by other detecting means,even postoperative pathology. PMID- 20359107 TI - [Monostotic fibrous dysplasia of the sphenoid sinus: two cases report and literature review]. AB - OBJECTIVE: To study the etiopathogenesis, clinical features, diagnosis and treatments of monostotic fibrous dysplasia of the sphenoid sinus. METHOD: Two cases of monostotic fibrous dysplasia of the sphenoid sinus without any symptoms was reported with relevant literature review. RESULT: No aggravation was found after 6 months-follow-up. CONCLUSION: The cranial fibrous dysplasia has low incidence rate with non-specific symptoms and high rate of misdiagnosis. The monostotic fibrous dysplasia of the sphenoid sinus without any symptom is rarely seen clinically. Imagiological examination, for example, CT and MRI, is valuable for the diagnosis of this disease. The histopathological evidence is absolutely necessary to make definite diagnosis. The conservative treatment may be chosen for the asymptomatic cases. Nasal Endoscopic surgery can not only remove the diseased region but also make diagnosis. The long-term follow-up should be carried out in all of these patients. PMID- 20359108 TI - [Epidemiological investigation of allergic rhinitis in the primary school students in grade three of Shihezi city]. AB - OBJECTIVE: To investigate the epidemic features of allergic rhinitis(AR)and correlative risk factors in Shihezi city, Xinjiang province, China. METHOD: A questionnaire survey on AR and airway diseases was conducted among 2 300 elementary school children in 12 schools, aged from 9 to 10 years old, from july 10 to 25, 2008 . in Shihezi city, Xinjiang province. Suspects of AR was identified by the survey, then they were recommended to specialist examinations for accurate diagnosis. Allergen skin tests were performed to explore the allergenic varieties of allergic rhinitis. Diagnosis criteria of AR were that of ARIA (Allergic rhinitis and its impact on asthma). RE-SULT: Two thousand two hundred and eleven questionnaires were returned. The response rate was 96.1% and 2205 questionnaires were available. The prevalence rate of AR in children aged from 9 to 10 was 12.56% (277/2 205) in Shihezi city. The difference of prevalence between female 13.76% (153/1112) and male 11. 34% (124/1093) was insignificant statistically(CHI2 = 2.924, P > 0. 05). The positive rate of the allergen skin test was 65. 3%. The most common allergen of allergic rhinitis were plants of the mugwort and house dust mite. According to the classification criteria of ARIA in 2001, of 155 children suffered from intermittent AR, 112 cases were mild and 43 cases were moderate-severe, while 122 suffered from persistent AR,110 cases were mild and 12 cases were moderate severe. 5.4% (15/277) patients with AR also had bronchial asthma. 25. 3% (70/277) of the children with AR had inherent predisposition. CONCLUSION: The prevalence rate of AR in children aged from 9 to 10 in Shihezi city is 12.56%. Strategy of prevention and treatment of AR can be worked out according to the epidemical feature of AR. PMID- 20359109 TI - [Analysis of histopathologic parameters and symptomatology in patients with chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery]. AB - OBJECTIVE: To estimate the predictable value of histopathologic parameters in chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery(ESS). METHOD: Symptomatology was rated in 53 patients 12 to 24 months after ESS. Specimens taken during the surgical procedure were examined and scored for eosinophils, goblet cells, lymphocytes, subepithelial thickening, subepithelial edema and submucous gland formation. The correlation between histopathologic parameters and postoperative symptoms was then evaluated. RESULT: The most common symptome after ESS were nasal obsruction, nasal secretion, discharge and sneezing. The correlation between goblet cells and sneezing, discharge, submucous gland formation and headache, subepithelial edema and postnasal secretion was significant (P < 0.05). CONCLUSION: Certain histopathologic parameters in CRSwNP are predictive of favorable response to ESS. PMID- 20359110 TI - [Comparative morphology of the two type's hair cells from saccule and utricle under inverted phase contrast microscope]. AB - OBJECTIVE: To explore more reliable standards for identifying vestibular hair cells of saccule and utricle prepared in studies with patch clamp technique under inverted phase contrast microscope. METHOD: The length and width of two type's hair cell's were measured besides the length of cilia, and all datas were analyzed statistically. RESULT: The width and length of cilia of two types hair cells in saccule and utricle from guinea pig were similar. The length of type I was longer than that of type II, so the ratio between length and width was larger and the ratio of the length between cilia and cell body was small. CONCLUSION: Two type's hair cells of saccule and utricle from guinea pig may be distinguished through the ratio of cell body's length and width even the ratio of the length between cilia and cell body, besides the standards before. PMID- 20359111 TI - [Study on the expression of Eotaxin and the role of histamine in allergic rhinitis]. AB - OBJECTIVE: To explore the expression of Eotaxin and the effect of histamine in allergic rhinitis model (AR), and aim to explore the pathogenesis of AR. METHOD: The AR models were established by application of ovum albumin in rats. The expression of Eotaxin in nasal mucosa, serum and nasal cavity lavage fluid, were observed before and after treatment of histamine or its antagonist by immunochemistry, RT-PCR and ELISA technique. RESULT: The expression of Eotaxin in nasal lavage fluid and nasal mucosa increased after treatment of histamine (P < 0.05). Contrarily, the expression of Eotaxin in nasal lavage fluid, nasal mucosa and serum decreased after treatment of the antagonist of histamine. CONCLUSION: Both histamine and its receptor can involve in the pathogenesis of AR by affecting the expression of Eotaxin. PMID- 20359112 TI - [Reconstruction with the anterolateral thigh flap interposition for defect after tumor resection of hypopharyngeal and cervical esophageal cancer]. AB - OBJECTIVE: To evaluate the effectiveness of the anterolateral thigh flap in reconstruction for the tissue defects of hypopharyngeal and cervical esophageal tumor resection. METHOD: Retrospective review of two clinical cases who underwent pharyngoesophageal reconstruction with the anterolateral thigh flap after tumor ablation. RESULT: No flap failure, fistula and stricture occurred in two patients. Two patients tolerated a regular diet. An esophageal voice was progressively acquired with the help of speech therapy. With followup for 16 and 41 months two patients were alive without tumor evolution. CONCLUSION: The higher success rate,lower complication, quick recovery, made the anterolateral thigh flap interposition is the ideal choice for pharyngoesophageal reconstruction. PMID- 20359113 TI - [Relationship between cranial nerve involvement in nasopharyngeal carcinoma and the prognosis]. AB - OBJECTIVE: To analyze the feature of cranial nerve involvement in nasopharyngeal carcinoma (NPC) and its relationship with the prognosis. METHOD: A total of 1892 patients who were diagnosed as NPC in our hospital from January 2002 to December 2003, of which the cranial nerve involvement was 183 (9.6%) patients, were analyzed the effect of cranial nerve involvement on the prognosis. RESULT: The percentage of cranial nerve involvement was 9.4%. The 5 year overall survival rate was 61.0%, disease free survival rate was 55.3%, local relapse free survival rate was 75.2% and distant metastasis free survival rate was 73.4%. Periods of cranial nerve involvement, clinical stage, the diameter of the lymph nodes, involvement of cavernous sinus, and the level of the recovery of cranial nerve involvement were significantly associated with prognosis in univariate analysis(P < 0.05). With multivariate analysis, the recovery level of cranial nerve involvement was the independent factor that affected the 5-year overall survival (RR = 2.087). The diameter of the lymph nodes and involvement of cavernous sinus were the independent factors that affected the 5-year distant metastasis-free survival (RR = 1.954 and 2.136, respectively). CONCLUSION: Periods of cranial nerve involvement and the level of the recovery of cranial nerve involvement were significantly correlated with prognosis. Involvement of cavernous sinus could increase the rate of distant metastasis. PMID- 20359114 TI - [Primary aspergillus laryngitis: report of six cases]. AB - OBJECTIVE: To discuss the distinctive clinical manifestation of primary aspergillus laryngitis. METHOD: Six cases of primary aspergillus laryngitis in our department were reviewed, among which 3 cases were diabetes patients, and were laryngeal mucosal barrier impairment. 2 cases were smoking, 2 cases were over use of voice and 1 case was gastro-pharyngeal reflux. Refractory hoarseness was the main clinical manifestation of all patients. The prophase treatment with antibiotics and glucocorticoid should breakdown the balance of flora and exacerbate the disease. RESULT: Stop using antibiotics and glucocorticoid and alter to oral administration of itraconazole in 2 to 4 weeks after final diagnosis can effectively cure the disease. No recurrence was found in 6 month to 4 years follow up. CONCLUSION: Diffuse hyperemia, pachynsis and scattered lamellar leukasmus of vocal cord were the characteristic physical findings of primary aspergillus laryngitis. Pathology is the major means to get the final diagnosis. Oral administration of itraconazole could be effective. PMID- 20359115 TI - [Clinical analysis of laryngeal neuroendocrine carcinoma]. AB - OBJECTIVE: To investigate the clinical characteristics and therapy of laryngeal neuroendocrine carcinoma (LNEC). METHOD: Ten cases of LNEC treated in our department were retrospectively analyzed. RESULT: Eight out of 10 cases were were atypical carcinoid: 1 case treated as supraglottic horizontal partial laryngectomy died 22 months after operation; 1 case was lost; the other 6 cases were followed up for more than 2 years. Two cases were small cell type, one received supra-cricoid partial laryngectomy-cricohyoidopexy (SCPL-CHP), neck dissection, and radiotherapy, but died after 14 months; the other was receiving radiotherapy. CONCLUSION: LNEC is a rare malignant tumor and the diagnosis relies on clinical characteristics, histopathological and immunohistochemistry examination. The different types of LNEC should give different treatment protocols. PMID- 20359116 TI - [Treatment and clinical analysis of laryngeal function preserving surgery in hypopharyngeal carcinoma]. AB - OBJECTIVE: To evaluate the therapeutic effect and the prognosis of the laryngeal function preserving surgery (LFPS) and total laryngectomy in hypopharyngeal carcinoma. METHOD: Ninety-three cases of laryngopharynx carcinoma were retrospectively analyzed from September 1974 to September 2006. Among which 57 cases were primary pyriform sinus cancer, 20 cases were postero-cricoid cancer and 16 cases were postero-pharyngeal wall cancer. 53 cases were treated by LFPS, and 40 cases were treated by total laryngectomy. The treatment effectiveness, complication, survival rate and repair materials were analysed. RESULT: Adopting Kaplan-Meier survival analysis, the 3-year survival rates were 69.9% and 5-year survival rates were 43.0%. The 3-year survival rates of LFPS and Non-LFPS were 73.6% and 67.5%, and the 5-year survival rates of LFPS and Non-LFPS were 49.1% and 32. 5%. There was no significant difference between the two groups (chi2 = 2.566, P > 0.05). Single element analysis indicated survival rates concerned with T-stage (chi2 = 9.764, P < 0.05), neck lymphatic transfer (chi2 = 10.472, P < 0.01) and the degree of pathological differentiation (chi2 = 25.894, P < 0.01). Cox regression analysis suggested that T-stage, the degree of pathological differentiation and whether going through the surgical operation were the independent element of the patient's prognosis. There was no significant difference between LFPS and No-LFPS in the neoplasms location, complication, neoplasms residuum and neoplasms recurrence. CONCLUSION: LFPS did not affect the survival rates and LFPS was feasible. LFPS can increase the living quality of laryngopharynx carcinoma patients. PMID- 20359117 TI - [Expression and clinical significance of Ang-2 and MMP-7 in laryngeal carcinoma]. AB - OBJECTIVE: To investigate the expression and clinical significance of Ang-2 and MMP-7 protein in laryngeal carcinoma tissue. METHOD: Immunohistochemical technique was used to detect the expression of Ang-2 and MMP-7 protein in 65 tissues of laryngeal carcinoma and 34 biopsies of adjacent non- cancerous tissue. The relationship between the expression of Ang-2 and MMP-7 and invasion, metastasis or prognosis in laryngeal carcinoma tissue was analyzed. RESULT: The positive rates of Ang-2 and MMP-7 were significantly higher in laryngeal carcinoma tissue than those in adjacent non-cancerous tissue (P < 0.05). The level of Ang-2 and MMP-7 expression had no significant correlations with the age and course as well as the smoking, drinking, histological differentiation of carcinoma and clinical classification (P > 0.05). While the expression of Ang-2 significantly differed between patients with different T stage and clinical stage (P < 0.05), and the expression of MMP-7 was notably correlated with the T stage, clinical stage and lymph node metastases (P < 0.05). There was a correlation between the expression of Ang-2 and MMP-7 (P < 0.05). The Kaplan-Meier survival analysis showed that patients with positive expression of Ang-2 had worse overall survival (P < 0.05). However, MMP-7 expression was not related to overall survival or disease-free survival (all P > 0.05). Cox regression analysis indicated that Ang-2 and MMP-7 expression were independent prognostic factors of laryngeal carcinoma. CONCLUSION: Overexpression of Ang-2 and MMP-7 was observed in laryngeal carcinoma and they might be served as an objective indicator for biological behaviour and prognosis. PMID- 20359118 TI - [To investigate the overexpression of Stat3 and Cyclin D1 in laryngeal neoplasm by immunohistochemistry]. AB - OBJECTIVE: To investigate the overexpression of Stat3 and Cyclin D1 in laryngeal neoplasm with immunohistochemistry method. METHOD: With immunohistochemistry method, we investigated the expression of Stat3 and Cyclin D1 in laryngeal neoplasm and analysis the relationship between Stat3 and clinical pathological factor. RESULT: Stat3 and Cyclin D1 overexpressed in laryngeal neoplasm tissue and they have positive relationship. CONCLUSION: Active Stat3 may promote the transcription of target gene Cyclin D1, which could accelerate carcinomatous change. PMID- 20359119 TI - [Expression of RAGE in laryngeal squamous cell carcinoma and clinical significance]. AB - OBJECTIVE: To study the expression and clinical significance of receptor for advanced glycation end products (RAGE) in laryngeal squamous cell carcinoma (LSCC). METHOD: immunohistochemical staining was used to detect the expressions of RAGE protein and semiquantitative method of reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression level of RAGE mRNA in LSCC tissues and laryngeal normal tissues of 37 cases, respectively. RESULT: The mRNA and protein expression of RAGE was significantly higher in LSCC than that in normal laryngeal tissues (P < 0.05), correlated with differentiation (P < 0.01), but not with tumor stage and location (P > 0.05). CONCLUSION: The expression levels of RAGE were significantly higher in LSCC than these in laryngeal normal tissues, RAGE is involved in differentiation of LSCC. PMID- 20359120 TI - [Temperament of children with vocal fold nodules]. AB - OBJECTIVE: To examine the temperament of children with vocal fold nodules. METHOD: To compare the temperament dimension and temperamental types of 42 children with vocal fold nodules with 46 vocally normal children, using Chinese children's Temperament Problem Screening system (CCTPSs). RESULT: The children with vocal fold nodules differed significantly from the comparison group in their temperament dimension's adaptability, intensity of reaction, mood value, persistency and temperamental types. CONCLUSION: There are more difficult and slow-to-warm-up children in patients with vocal fold nodules than vocally normal children. PMID- 20359121 TI - [Studies on inhibitive effect of low-voltage electrochemotherapy on head and neck cancer-bearing nude mice]. AB - OBJECTIVE: To analyse the therapie effect of low-voltage electrochemotherapy (EP) on the head and neck cancer. METHOD: YCU-N861 human head and neck cancer cells were subcutaneously inoculated in the neck of nude mice to establish tumor bearing models. Then the mice were treated with bleomycin (BLM, 20 microg per mouse), accompanied with electric stimulation (50 V or 100 V). RESULT: BLM treatment applied with EP can significantly inhibit the proliferation of tumor cells than BLM or EP treatment separately (P < 0.01). The tumor volume, the mitotic index (MI) and the labeling index (LI) of Ki67 in BLM+EP group were all obviously decreased than BLM group, EP group and control group (P < 0.01). CONCLUSION: Low-voltage electrochemotherapy can offer promising method in the local treatment of head and neck cancer. PMID- 20359122 TI - Commentaries of the 50th anniversary of the relaunch of the Chinese Physiological Society in Taiwan. Dedicated to an academician of the Academia Sinica and Professor Emeritus Hwai-Sze Fang of the Department of Physiology at the National Taiwan University in Taiwan for his 95th birthday. PMID- 20359123 TI - The role of mast cells in citric acid-induced airway constriction and cough. AB - Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, compound 48/80 pretreated animals were divided into 2 parts; the first one was used to test the role of exogenous leukotriene (LT) C4, while the second one to test the role of exogenous histamine. Decreases in respiratory compliance (Crs) and forced expiratory volume in 0.1 sec (FEV0.1) were used as indicators for airway constriction in anesthetized guinea pigs. CA-induced cough was recorded for 12 min using a barometric body plethysmograph in conscious animals. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining lung tissue or arterial plasma histamine concentration in animals. Exposure to CA induced marked airway constriction and increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced airway constriction and cough. Injection of LTC4 or histamine caused a significant increase in CA-induced airway constriction and cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in lung tissue and plasma histamine concentrations, which were blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction and cough via perhaps mediators including LTs and histamine. PMID- 20359124 TI - From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is the most devastating form of acute lung injury (ALI) or pulmonary edema (PE). We presented the experimental studies and clinical investigations of two serious forms of ALI. Drastic and severe PE could be induced by intracranial hypertension or cerebral compression (CC). The CC-induced PE was attributed to overactivation of the medullary sympathetic mechanism. Sympathetic vasoconstriction of the systemic and pulmonary resistance and capacitance vessels caused shift of blood volume from the splanchnic vascular beds to the lung. The hemodynamic changes led to systemic and pulmonary hypertension. Consequently, left ventricular failure as evidenced by dramatic decline in aortic flow with a slow decrease in pulmonary flow resulted in pressure and volume loading in the pulmonary circulation. These changes finally produced severe alveolar flooding and sudden death. Vasodilators such as sodium nitroprusside or nitroglycerin were capable of reducing the CC-induced pulmonary pathology and hemodynamic alterations. Fat embolism syndrome (FES) is a serious clinical problem in patients suffering from long bone fractures. ARDS may develop and cause mortality. Our laboratory reported a total of 14 subjects associated with FES and died of ARDS. We also developed a simple technique to produce FES. Corn oil was mixed with distilled water to form fatty micelles. Intravenous administration of or introduction of fatty micelles in anesthetized rats or isolated perfused lungs caused severe alveolar damage. Our clinical observation and animal experimentation revealed that infusion of fatty acids caused physical phase, resulting in microvascular obstruction accompanied by pulmonary hypertension and increased capillary permeability. Thereafter, the lipases in the lung hydrolyzed the neutral fat and released free fatty acids and biochemical mediators which were toxic to the lung. Our data have suggested that nitric oxide (NO), inducible NO synthase (iNOS), phospholipase A2, free radical and inflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta and interleukin-6) are involved in the biochemical phase of FES with ARDS. The alveolar macrophages are the major source of iNOS. Later study also found that neutrophil elastase and myeloperoxidase were elevated following fat embolism. N acetylcysteine (an antioxidant), and NOS inhibitors such as Nomega nitro-L arginine methyl ester (L-NAME), S-methylisothiourea (SMT) or L-N6 (1-iminoethyl) lysine (L-Nil) were able to abrogate the FES or the fat embolism-induced changes. PMID- 20359125 TI - Somatosympathetic reflex and acupuncture-related analgesia. AB - Both acute and chronic pains correspond to nociceptive substances (NSs), which are naturally produced and metabolized by the organism experiencing the pains. The accumulation of NSs in regional tissues triggers a series of pathophysiological reactions and initiates certain threats to the health and the quality of human life. Pharmacological intervention is the most popular treatment for pain relief, which is achieved by either reducing the production of NSs or blocking the transmission of nociceptive signals through the nervous system, but no drug has been developed for the elimination of NSs. Therefore, improving blood circulation to eliminate NSs in painful tissues is an alternative strategy for pain relief. Acupuncture has been proved to be effective for the treatment of certain kinds of pain, but the mechanisms therein remain unclear. The effectiveness of acupuncture analgesia is also variable owing to the uncertainty surrounding the mechanism and the poor standardization of the technique. There is some evidence that acupuncture may induce pain relief by changing the regional blood flow through somatosympathetic reflex (SSR). Therefore, when exploring the mechanisms of SSR in detail, it is helpful to clarify the mechanisms of acupuncture analgesia and to develop a more standardized and effective protocol for acupuncture analgesia. Increasing evidence has suggested that both sympathetic activity and stimulation-induced SSR are differentially controlled in an organ-specific and activity-dependent manner. Vasomotor outflow, which involves the regulation of impaired regional blood circulation, is also differentially controlled in response to specific somatic stimulation. Therefore, we vigorously review the relations between SSR and acupuncture-related analgesia so that we can develop a targeted pain therapy where in certain areas of the body undergo site-specific somatic stimulation, which in turn, can adjust the impaired regional blood circulation. PMID- 20359126 TI - Modulation of propofol on the effects of blood pressure and firing activity of related neurons in the medulla. AB - Many studies have demonstrated that the ventrolateral medulla (VLM) plays an important role in the maintenance of systemic arterial pressure (SAP) and vascular tone. The VLM is divided into rostral (RVLM) and caudal (CVLM) portions which play opposing roles in regulating cardiovascular functions. The purposes of this study are to explore the relationship of fibers projecting between the RVLM and CVLM, and to investigate the effect of propofol (PPF, 2 mg/kg), an anesthetic agent, on modulating their neuronal firing rate (NFR). Forty-four adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of SAP and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. Microinjection of glutamate (Glu, 3.0 nmol/30 nl), kynurenic acid (Kyn, 3.0 nmol/30 nl), gamma-aminobutyric acid (GABA, 4.0 nmol/30 nl), or bicuculline (Bicu, 4.0 nmol/30 nl) into the RVLM produced SAP increases or decreases, but did not significantly change the NFR in the CVLM. This occurred even after intravenous administration of PPF. This shows that there are few fiber projections from the RVLM to the CVLM. Conversely, microinjection of Glu, Kyn, GABA or Bicu into the CVLM produced SAP changes, and the NFR in the RVLM was significantly changed. These changes were more significant after intravenous administration of PPF. These results show that there are more fibers projecting from the CVLM to the RVLM and fewer fibers projecting from the RVLM to the CVLM to affect the SAP and its NFR. PMID- 20359127 TI - Protection of ischemic preconditioning on renal neural function in rats with acute renal failure. AB - We tested whether tolerance induced by ischemic preconditioning (IPC) in kidneys was related to renal nerves. Experimental acute renal failure (ARF) in a rat model was induced for 45 min of left renal arterial occlusion (RAO), followed by 6 or 24 h of reperfusion (ischemic reperfusion (I/R) group). The episode of IPC was four cycles of 4 min of RAO at 11 min intervals and then the I/R injury was treated as above (IPC-I/R group). After 6 h of reperfusion, polyuria was found in the I/R group associated with an enhancement of afferent renal nerve activity (ARNA) and a reflexive decrease in efferent renal nerve activity (ERNA). Changes in nerve responses were related with a reduction in neutral endopeptidase (NEP) activity and an increased release of substance P (SP). After 24 h of reperfusion, the I/R group showed oliguria which was associated with a lower ARNA, hyperactivity of ERNA and a nine-fold increase in SP release due to a further 52% loss in NEP activity. Prior IPC treatment did not affect the changed ischemia induced excretory and nervous activity patterns during the first 6 h of reperfusion, but normalized both responses in the kidneys 24 h after ischemia. The IPC-mediated protection in oliguric ARF was related to the preservation of NEP activity to only 25% loss that caused an increase of SP amounts of only three fold and a minor change in neurokinin 1 receptor (NK-1R) activities. Finally, both excretory and sensory responses in oliguric ARF after saline loading were significantly ameliorated by IPC. We conclude that IPC results in preservation of the renal sensory response in postischemic kidneys and has a beneficial effect on controlling efferent renal sympathetic nerve activity and excretion of solutes and water. PMID- 20359128 TI - Enhancement of superoxide dismutase activity in rat lungs after hypoxic preconditioning. AB - Ischemic preconditioning has been proved to reduce tissue damages and benefit subsequent organ transplantation. Chronic hypoxic preconditioning was found to increase the levels of lung antioxidants. This study was to test the hypothesis that levels of lung antioxidants might increase after hypoxia which may counteract the insults of free radicals. Female Wistar rats were kept in an altitude chamber (380 torr) 15 h a day for 4 weeks (hypoxia-adapted). Controls were kept at room air pressure (sea-level). After hypoxic preconditioning, no significant difference in the levels of the oxidative markers, malondialdehyde, thiobarbituric acid reactive substances and isoprostane was seen in the lungs of the hypoxia-adapted rats compared to the sea-level controls. Both the activity and protein level of manganese superoxide dismutase were higher in hypoxia adapted lungs. Lung manganese superoxide dismutase mRNA levels, determined by real-time RT-PCR, were not significantly different in the two groups of rats. When isolated saline-perfused lungs were prepared and treated with xanthine (500 microM) and xanthine oxidase (5 mU/ml), and the levels of free radicals in the perfusate determined by chemiluminescence, less chemiluminescence was seen in the hypoxia-adapted lung perfusate. When the vascular response was determined in this same preparation before or 45 min after xanthine/xanthine oxidase treatment, the filtration coefficient was increased in the sea-level lungs but not in the hypoxia-adapted lungs. We conclude that an increase in superoxide dismutase activity and protein levels is one of the benefits of hypoxic preconditioning. PMID- 20359129 TI - Enhancement of vascular formation but not improvement of ventricular function of infarcted rat hearts by a high dose of adenovirus-carried VEGF transgene. AB - The purpose of this study was to examine the influence of adenovirus-carried VEGF165 transgene at 5 x 10(10) pfu (Ad-VEGF) on vascular formation, cardiac geometry and ventricular function in infarcted hearts of the rat and to explore the mechanism of Ad-VEGF-mediated actions on ventricular function by quantitative proteomic analysis. Seven days after coronary occlusion, intramyocardial injection with normal saline (vehicle control), adenovirus-carried beta galactosidase gene (Ad-LacZ, vector control) or Ad-VEGF to infarcted hearts was conducted. Seven days after intramyocardial injection, ventricular function, cardiac morphology and vascular density were assessed after echocardiographic analysis and immunohistological staining. One dimensional gel electrophoresis coupled with stable isotope dimethyl labeling and LC/MS/MS was used to quantify the abundance ratio of each protein pair in Ad-VEGF- and Ad-LacZ-treated hearts. Our data indicated that both Ad-VEGF and Ad-LacZ increased arteriolar densities. However, the former increased arterial densities but the latter did not. Compared with the vehicle control, Ad-LacZ reversed occlusion-induced wall thinning and functional impairment but Ad-VEGF did not. Quantitative proteomic analysis showed increased ratios of plasma proteins (such as albumin) and oxygen carriers (such as myoglobin) by Ad-VEGF and decreased ratios of proteins involved in glycolysis, calcium homeostasis and lipolysis by Ad-VEGF. Taken together, our functional, morphological and proteomic data suggest that intramuscular delivery of Ad-LacZ at higher doses may improve ventricular function and wall thinning with arteriolar formation. Excessive amounts of VEGF by Ad-VEGF may offset Ad-LacZ induced improvement in ventricular functions by interfering with calcium homeostasis and lipolysis in infarcted hearts. PMID- 20359130 TI - Effects of serotonin on acid secretion in isolated rat stomach: the role of 5-HT3 receptors. AB - Serotonin (5-hydroxytryptamin; 5-HT) content has been measured using high performance liquid chromatography with electrochemical detection (HPLC-ECD). The distributions of 5-HT-containing cells and 5-HT3 receptors have been determined with specific antibodies against 5-HT and 5-HT3 receptors, respectively. The effect of serotonin on acid secretion has been studied using an isolated rat stomach model. It has been shown that 5-HT concentrations in the fundus, mucosal layers of the corpus, remaining layer of the corpus and antrum are approximately 152, 498, 1494 and 972 nmol/mg protein, respectively. The distribution of 5-HT containing cells is concentrated in the enteric plexus and enterochromaffin (EC) cells in the deep mucosal layer. Immunoreactivity to 5-HT3 receptors is localized in numerous neurons of the myenteric and submucosal plexus and concentrated in the neuronal plasma membrane, submucosa, endocrine cells and lamina propria. In the present study, the effect of 5-HT on gastric acid secretion was investigated on an everted preparation of isolated rat stomach. 5-HT at 1-100 microM reduced acid secretion stimulated by oxotremorine while 10 microM 5-HT did not modify the basal secretion of gastric acid. We further showed that 10 microM 5-HT reduced acid secretion and pepsin output stimulated by oxotremorine, histamine and pentagastrin; among the 5-HT receptors agonists tested, 2-methyl-5-HT (1-10 microM), a 5-HT3 receptor agonist, inhibited oxotremorine-, histamine- and pentagastrin-stimulated acid secretions, and this inhibitory effect was blocked by 1 microM MDL 72222, a specific 5-HT3 receptor antagonist. These results suggest that 5-HT is released from serotoninergic neurons, their processes and EC cells. The effect of 5-HT mediated by 5-HT3 receptors involves distinct neuronal and non-neuronal pathways which modulate gastric acid secretion. PMID- 20359131 TI - Reduction of hexa(sulfobutyl)fullerence on oxidative injury by xanthine and xanthine oxidase in isolated rat lungs. AB - The present study was undertaken to evaluate whether some fullerenols could effectively reduce direct damages of free radicals produced by xanthine/xanthine oxidase (X/XO) in isolated rat lungs. METHODS: Female Wistar rats (205 +/- 4 g) were used in studies in pulmonary vascular response to the challenge of xanthine/xanthine oxidase by an isolated-perfused lung method. Free radicals were determined by chemiluminescence (CL) to confirm the release of free radicals after X/XO treatment. The CL count in the lung perfusate was 737 +/- 213 (CL/10 sec); 5 min and 45 min after X/XO administration, the CL counts were 3,778 +/- 425 (CL/10 sec) and 1,183 +/- 193 (CL/10 sec), respectively. Challenge with X/XO caused a mild but significant increase in pulmonary arterial pressure (P(pa)) and a marked increase of filtration coefficient (K(fc)). The pretreatment of Hexa (sulfobutyl) fullerence antioxidant, K(fc) became insignificantly increased in pretreated lungs. In conclusion, We found that hexa(sulfobutyl) fullerene, but not Co60(glucosamine)6, nor superoxide dismutase could attenuate the oxidative stress, judged from the attenuated increase in pulmonary filtration coefficient after challenge. PMID- 20359132 TI - The gender gap in Italian Academic Medicine. PMID- 20359133 TI - [Employment of psychiatrically disabled people. The Lavoro LiberaMente project]. AB - BACKGROUND: The complexity of giving psychiatrically disabled persons access to work is well known. The percentage of persons thus defined who are on the provincial unemployment lists is constantly increasing. OBJECTIVES: The 'Lavoro Liberamente" ('I work freely') project is aimed not only at enabling a number of psychiatric patients to gain access to work but to do so by experimenting with a network methodology that includes the various agencies that can contribute to a successful outcome. METHOD: The project was developed in various stages- psychiatric services and company awareness campaigns and task-definition, candidate selection, skills assessment, and work placement--all aimed at finding and maintaining employment. RESULTS: After a thorough preparatory phase, 19 psychiatrically disabled persons were placed in 14 companies. When the apprenticeship was concluded, 13 of them were hired. CONCLUSIONS: Considering the short time-frame--about one year between candidates being selected and finally recruited--the ratio between the number of disabled people recruited and those placed was satisfactory. This result should be interpreted positively because, even taking into account some of the most sensitive issues that surfaced and were analysed, it shows that access of the psychiatrically disadvantaged to work is possible if all involved people work synergistically, each according to their responsibilities and knowledge, and on condition that a recognised management of each individual project exists. Within such a network synergism, it is even possible to identify some tasks that are the responsibility of the Occupational Health Physician, therefore further contributing to the overall success of placements. PMID- 20359134 TI - [Work-related musculoskeletal disorders: appropriateness of the requests of clinical consultation in occupational medicine departments]. AB - BACKGROUND AND OBJECTIVES: The authors analyze the results of the clinical assessment of patients suffering from suspected work-related muscular-skeletal disorders (WMSDs), observed during the course of 2008 in the Department of Occupational Medicine of the Ospedali Riuniti hospital in Bergamo. The aim was to analyse the appropriateness of the requests of clinical consultation, comparing the cases sent by general practitioners and by occupational physicians. METHODS: We assessed 149 patients (mean age 47 years, DS 9.4; mean work seniority 29.5 years, DS 10.2), investigating 218 disorders in different muscular-skeletal segments. The majority of patients (63.7%) for whom a clinical consultation was requested were sent by general practitioners, 32.9% by occupational physicians, 3.4% by the National Insurance Institute for Occupational Accidents and Diseases (INAIL). The assessment was made in two steps: first a clinical and instrumental definition of the disorders, prescribing the necessary medical investigations were the diagnosis was not already clear; secondly a definition of the aetiology, requesting documentation about working conditions when this was not clear from the medical history, experience and literature, or making an inspection. RESULTS: A majority of the patients (40.2%) were employed in the construction industry. Regarding symptoms, 54.4% of the subjects reported low back pain, 74.5% upper limb disorders (some of the patients reported several problems in different segments). The clinical diagnosis was already clear at the first consultation for 62.8% of all cases; for the other 37.2% it was necessary to prescribe some instrumental examinations or specialistic (neurologic, physiatric, orthopaedic) medical examinations. We concluded for a diagnosis of WMSDs in 99 (45.4%) of the 218 cases (50% of the assessments requested by occupational physicians, 45.3% of the assessments requested by general practitioners). The most frequent reason for rejecting an occupational aetiology was the lack of correlation between type of disease and occupational exposure, both for patients referred by occupational physicians (58.1%) and by general practitioners (51.8%). DISCUSSION: The results demonstrated that the appropriateness requests for clinical consultation was identical for general practitioners and occupational physicians. All physicians showed a high degree of attention for the upper limb disorders, which is a topical subject of great epidemiological interest. General practitioners and occupational physicians need to take more advantage of the diagnostic support and clinical evaluations offered by Occupational Medicine Departments and Universities for WMSDs. PMID- 20359135 TI - [Exposure to air pollutants in the city of Bari]. AB - BACKGROUND: Air pollution leads to increased levels of morbidity and mortality for cardiovascular and respiratory diseases in populations living in urban environments. OBJECTIVES: Our study tested the possibility of using sampling techniques that are typical of industrial hygiene to measure exposure to atmospheric pollutants and using personal samplers for concentrations of certain pollutants to which an ordinary resident of Bari is exposed on a daily basis. METHODS: We monitored dusts (PM10, PM2.5), CO, CO2, humidity, ventilation and noise, by dynamical sampling along a route on foot, bicycle, motorbike and automobile and then compared the results with data provided by fixed stations distributed in the municipality of Bari. RESULTS: By comparing our data with those values provided for by the law, we found out that the concentrations of all pollutants resulted to be higher than 50 microg/m3, with the exception of the measurements carried out along the route by car. The measurements of PM2.5 were, on average, similar to the values of PM10 for the route on foot, but they were totally different for the measurements made along the route by car, bicycle and motorbike. Moreover, comparing our data with those obtained from the municipal network of fixed stations, we found that results provided by our measurements were higher for PM10. CONCLUSIONS: Considering that compliance with the limits set by law refers to average values over 24 hours, we can conclude that those hours in which pollutant concentration reaches a risk level shall be considered especially regarding groups of people with respiratory disorders. PMID- 20359136 TI - [Validation of a screening method for occupational bladder cancer]. AB - BACKGROUND: Transitional bladder cancer is the most frequent malignant urinary neoplasm. Occupational exposure to aromatic amines and to polycyclic aromatic hydrocarbons are the main risk factors, in addition to cigarette smoking, recurrent inflammatory diseases of the urinary tract, consumption of certain drugs and a positive family history. Nevertheless cases of work-related bladder cancer are poorly identified in Italy. OBJECTIVE: The aim of this study is to assess the screening accuracy of a short structured interview to detect suspected cases of occupational bladder cancer, which may be confirmed in a second step assessment by an occupational physician. METHODS: The study sample consisted of 94 transitional bladder cancer patients, first hospitalised in 2004 and 2005 at the Department of Urology of the Ospedale di Circolo - Fondazione Macchi, in Varese, Italy. Based on data collected through a simple structured interview, it was possible to estimate two occupational exposure indices: one taking into account only the length of employment in industrial settings (DS Index) and the other considering job title in addition (DSM Index). For all cases a second-step assessment by an occupational physician (gold standard) made it possible to establish the occupational origin of cancer and to assess accuracy. RESULTS: Satisfactory values of the area under the ROC curve were found for both indices (AUC 0,81 for DS and 0,87 for DSM). In particular at the same level of sensitivity (90%), the DSM Index showed a better specificity (72%) in comparison to the DS Index (64%). CONCLUSIONS: The short structured interview proposed here proved to be a valuable tool for general practitioners and urologists to detect cases of bladder cancer of suspected occupational aetiology, which can be referred to an occupational physician for further investigations. PMID- 20359137 TI - [Fertility changes in women working in greenhouses]. AB - BACKGROUND: Greenhouse workers (GW) are exposed to environmental contaminants, including pesticides, that may not only cause known immediate effects such as acute poisoning, but also long-term effects related to chronic exposure to low dosages, a problem that has not been extensively studied This study investigated the relationship between fertility changes and exposure to pesticides in a group of women working in greenhouses. STUDY GROUP AND METHODS: The analysis is based on a retrospective cohort of 145 women working in greenhouses located in the province of Latina, Lazio Region, Italy, who were exposed to pesticides at the time of their first pregnancy. Information on health status, lifestyle, work activity, reproductive history and some confounding factors (age, smoking, alcohol abuse, drug consumption) were collected using a questionnaire. Exposure to pesticides was classified in two levels (high or low) according to the work task and the length of exposure. Changes in fertility were measured in terms of time to pregnancy (TTP), that is the number of non-contraceptive cycles that it takes a couple to conceive. A control group was selected among public administration employees in the same province. The difference in average TTP between exposed and non-exposed groups was analysed by using Student t-test. A Cox proportional hazard model was used to compare TTP between the two groups after correction for confounding factors. RESULTS: In the high-level exposure group average TTP was 10.8 months (+/- 2.0), among the non-exposed average TTP was 6.2 months (+/- 1.0). The difference between exposed and non-exposed was thus 4.6 months (p<0.05). Comparison of the distribution of TTP between the high-level exposure group and nonexposed resulted in a hazard ratio of 1.27 (I.C. 95%: 1.03 1.79); the same analysis using the low-level exposure group and non-exposed group yielded a hazard ratio of 1.12 (I.C. 95%: 0.67-1.87). DISCUSSION: The study showed reduced fertility, in terms of TTP, in the population exposed to pesticides. Among GW, TTP was as much as 50% higher than for the control group. Controlling for confounding factors, the study confirmed an increase in risk for the exposed group. The issue under investigation, however, is complex as health status is not the only factor that needs to be taken into account in studies of reproductive health; emotional status as well as congenital and acquired factors may also have a notable impact on women's fertility. Occupational exposure, therefore, can be said to be a condition requiring careful analysis while bearing in mind that other factors may influence the outcome. PMID- 20359138 TI - Toxicity of monazite particulates and its attenuation with a complex of bio protectors. AB - BACKGROUND: Workers employed on mining, processing and storage of monazite are at risk of exposure to dust with expected adverse health effects. OBJECTIVES: To study the adverse health effects of monazite particles in experiments on rats and to test the possibility of attenuating these effects. METHODS: Outbred white rats were injected intratracheally with a suspension of ground monazite concentrate (MC) in order to investigate the cellular response of the lower airways 24 hours later and the organism's status 6 months after the injection. The bio-protective complex (BPC) tested in these experiments consisted of glutamate, an iodine preparation, methionine, a polyvitamin-polymineral composition, and/or "Eicosavitol" (fish oil preparation rich in PUFA, predominantly of the omega 3 group). Bio-protectors were administered together with the rat food and drink daily for one month before the MC injection in the short-term experiment, or over 6 months after such injection in the long-term experiment. RESULTS: MC induced manifestations of its cytotoxicity, fibrogenicity and systemic toxicity as well as genotoxicity. The tested BPC attenuated virtually all these effects. Although a similar protective potential of "Eicosavitol" against almost all of them was lower compared with that of BPC, combining BPC with "Eicosavitol" provided, as a rule, the greatest protective effect. CONCLUSION: It may be assumed that the many sided adverse effects of MC on the organism is due, at least partially, to the presence in its composition of not only rare earth elements but also of natural radioisotopes of the thorium and uranium families. The combination of the bio protectors tested was highly effective and may be recommended for administering in periodic preventive programmes to exposed workers. PMID- 20359139 TI - [Hand-arm vibration syndrome in a nurse carrying out gypsum cutting operations]. AB - BACKGROUND: A professional nurse, employed mainly on gypsum cutting operations, developed a hand-arm vibration syndrome with Raynaud's phenomenon, neurosensitive disorders and impairment of the bone and joints apparatus of the hand and arm. METHODS: The nurse underwent diagnostic investigations (cold test, X-ray of the upper limbs, blood tests); also the vibration levels transmitted from instrument were measured and the exposure times were established. RESULTS AND CONCLUSIONS: Clinical investigations showed the presence of a hand-arm vibration syndrome with secondary Raynaud's phenomenon and environmental surveys revealed very high vibration levels, such as could be associated with the disease with a causal relationship. In the literature no reports exist of the vibration syndrome being associated with health care workers in orthopaedic departments. The case described in this study occurred because of peculiar organisational factors that most likely have never occurred in other hospitals or orthopaedic departments. PMID- 20359140 TI - Nursing education: CH versus CEU--which is correct? PMID- 20359141 TI - Practical review of pharmacology concepts. AB - Pharmacology concepts are used routinely in nursing practice. These concepts may be as simple as drug names and side effects, or as complex as pharmacokinetics or pharmacodynamics. All play major roles in drug efficacy and safety. A practical review of pharmacology, including pharmacokinetic and pharmacodynamic concepts, will be presented. PMID- 20359142 TI - Individual variations in drug responses. AB - This article provides an overview of the modifiable and non-modifiable variables that influence drug responses. Knowledge of these issues need to be known by nurses to assure adequate medication is prescribed and treatment adherence occurs. PMID- 20359143 TI - Update on the pharmacologic management of overactive bladder: the present and the future. AB - Overactive bladder (OAB) is a common condition, affecting approximately 17% of females and males 40 years of age and older. Historically, oxybutynin was the only medication approved for use in the management of OAB. Over the past decade, several new antimuscarinics have been approved for the treatment of OAB. Although all are deemed to be effective in improving the bothersome symptoms of OAB, they differ in their molecular properties, metabolism, and tolerability/side effect profile. A greater understanding of the pathophysiology of OAB has led to approved and investigative therapies to treat refractory OAB, such as neuromodulation and intravesical injection of Botulinum toxin, respectively. A variety of pharmacologic agents are in clinical trials for OAB that target different components of bladder function, such as the urothelium, the afferent sensory nerve pathways, and the central nervous system. It is the intent of this article to highlight these aspects of OAB management. PMID- 20359144 TI - New therapeutic strategies for renal cell carcinoma. AB - Treatment options for renal cell carcinoma have changed dramatically since 2005 when the U.S. Food and Drug Administration approved six new therapies. These agents inhibit pathways relevant in the pathogenesis of renal cell carcinoma, interfering with tumor angiogenesis, cell progression, and metastasis. Understanding the pharmacology of these agents is necessary for clinicians to provide appropriate patient education, assure adherence with the treatment plan, and facilitate early identification and intervention for side effects. These activities will provide positive clinical outcomes. PMID- 20359145 TI - The essential role of the clinical research nurse (CRN). AB - In an age of increasing focus on expanding the opportunity of clinical research trial participation to broader patient populations, the clinical research nurse (CRN) has become an essential member of the clinical research team. The CRN is responsible for many roles and aspects of clinical trial management. Clarification of these roles and responsibilities will be provided in this article. PMID- 20359147 TI - Adding to the evidence base: Impact of penile injections on men with erectile dysfunction after prostatectomy. PMID- 20359146 TI - Impact of penile injections on men with erectile dysfunction after prostatectomy. AB - Penile injection has been shown to be an effective treatment for erectile dysfunction (ED) following prostatectomy, yet it is not commonly used by these men. The purpose of this study was to determine the impact on quality of life of injection treatment of ED in men after prostatectomy, as well as barriers to use. The study used a one-group, pretest/posttest design, with data collection before treatment, and one and three months after treatment. Use of penile injections resulted in improved erectile function, sexual self esteem and confidence, and satisfaction with the sexual relationship. Side effects reported were pain, priapism, bruising, and curvature or the penis. PMID- 20359148 TI - Update on global climate change. AB - Global climate change brings new challenges to the control of infectious diseases. Since many waterborne and vector-borne pathogens are highly sensitive to temperature and rainfall, health risks resulting from a warming and more variable climate are potentially huge. Global climate change involves the entire world, but the poorest countries will suffer the most. Nations are coming together to address what can be done to reduce greenhouse gas emissions and cope with inevitable temperature increases. A key component of any comprehensive mitigation and adaptation plan is a strong public health infrastructure across the world. Nothing less than global public health security is at stake. PMID- 20359149 TI - Under-hyped and over-hyped drug-dietary supplement interactions and issues. AB - Complementary and alternative medicine utilization continues to abound, as does the use of prescription medications. Thus, real and hypothetical concerns exist for potential drug-dietary supplement interactions. Several supplements, including kava and St. John's Wort, have the potential for adverse medication interactions, but there are also several supplements, such as fish oil, garlic, ginkgo, pygeum, and saw palmetto, whose adverse potential may have been embellished. Still, there are other common supplements, such as vitamin D, that are enjoying an impressive amount of attention and consumption but their potential for current or future toxicity seems considerable and concerning, especially with individuals with multiple non-communicating practitioners. Regardless, it is important to continue to monitor dietary supplements (not just herbal products) that may have interaction and toxicity issues, and to also educate patients and clinicians on other supplements that do not have these issues despite an earlier concern and avoidance based on a minimal number of laboratory studies or case reports. PMID- 20359150 TI - Getting ready for certification: basic cystoscopy equipment and supplies. PMID- 20359151 TI - [Croatian guidelines for use of enteral nutrition in Crohn's disease]. AB - Nutrition has an important role in the management of inflammatory bowel disease (IBD), especially in patients with Crohn's disease (CD). This role includes the prevention and correction of malnutrition, the prevention of osteoporosis and the promotion of optimal growth and development in children. In active Crohn's disease, nutritional therapy (in the form of enteral feeding) is an effective primary therapy for pediatric patients. Studies have shown that there is no difference in the efficacy of elemental, oligomeric and polymeric enteral formulas. Therefore, the use of polymeric formula is recommended because of higher palatability, better acceptance by patients, lower rate of complications and lower cost when compared with other enteral formulas. Today we have knowledge that some nutrients which are added to modified special enteral formulas have almost pharmacological terapeutic potential in the management of inflammatory bowel disease. Novel nutritional therapeutic strategies for inflammatory bowel disease, such as transforming growth factor-beta-enriched (TGF-beta2) enteral feeding, showed beneficial effects in several clinical studies. Croatian guidelines for enteral nutrition in Crohn's disease have been developed by interdisciplinary expert group of Croatian clinicians involved with inflammatory bowel disease. The guidelines are based on evidence from relevant medical literature and clinical experience of working group. PMID- 20359152 TI - [Succinylcholine use by anesthesiologists in Croatia--is it really abandoned?]. AB - The aim was to establish the prevalence of succinylcholine use among Croatian anesthesiologists in adult elective and emergency surgery, as well as in pediatric surgery, regarding gender, position, working place, and working experience of physicians. The anesthesiologists were expected to express their personal opinions regarding the drug, as well as experienced side effects in their own clinical practice. A total of 125 anesthesiologists (out of 590 in Croatia) from both university and county hospitals in Croatia anonymously filled out the questionnaire regarding the use of succinylcholine (Appendix 1). The questionnaire was structured to assess the use of succinylcholine in adult elective and emergency surgery, and in pediatric anesthesia, to obtain the reasons for the preference or rejection of succinylcholine, and information about observed side effects. The differences in use regarding gender, position, working place, and working experience were tested using chi-squared test and Fisher's exact test. p < 0.05 was considered significant. Vast majority (approximately 70%) of anesthesiologists in Croatia still use succinylcholine. The percentages of anesthesiologists that never use succinylcholine in adult elective, adult emergency and pediatric surgery were 20%, 6%, and 31%, respectively. There were no significant differences in the use of succinylcholine regarding position, working place, and working experience, but male anesthesiologists used it less frequently in pediatric anesthesia compared with their female colleagues (chi2 = 5.08; p = 0.02). Forty-two per cent never experienced a complication from the drug use. The most frequently reported side effects were bradycardias (67%) and myalgias (54%), followed by prolonged blockade (33%), and allergy (33%). Asystole was reported by 10% of the respondents. In conclusion, succinylcholine is still widely used by anesthesiologists in Croatia. The majority of surveyed physicians were aware of its possible dangerous adverse effects, but still use it in certain situations. Therefore, indications and contraindications for its use deserve expert consensus guidelines based on the available scientific evidence. PMID- 20359153 TI - [The ultrasound characteristics of kidneys in children and adolescents with diabetes mellitus type 1]. AB - The aim of the study was to compare ultrasound findings of morphometric measurements and registration of Doppler signs of kidneys between children and adolescents with diabetes mellitus type 1 (DMT1) with microalbuminuria, and metabolic control with duration of the disease. Retrospective-prospective study included 80 patients, who got DMT1 in the age from 2 to 16 years. In relation to the duration of the disease, all patients were divided into two groups: the first was whose illness had lasted less than 10 years, the second group was with duration of DMT1 more than 10 years. In patients with duration of DMT1 more than 10 years, the frequency of microalbuminuria, pathological findings of the volume of right kidney, and higher HbA1C were significantly greater. The significant difference was found in the frequency of pathological findings of the resistance index (RI) in the interlobar arteries in both kidneys. Alongside microalbuminuria, monitoring the dimension and volume of the kidneys may indicate the existence of the early phases of diabetic nephropathy. PMID- 20359154 TI - [Acute colonic pseudo-obstruction with complication--case report]. AB - This case report examines the surgical treatment of megacolon and its complications in a 17-year-old male patient. He was examined in the surgical emergency unit because of severe abdominal pain and absence of stool for one week. Detailed history revealed that the patient had difficulties in defecation from the early childhood. Sphincter control was not established by the age of five. During hospitalzation as a child, the diagnosis of congenital megacolon was excluded (pathohistological examination of rectal biopsy material showed normal findings). He was followed-up regulary, had stool every four to five days and few times received laxatives to relieve constipation. The patient was hospitalized at the Department of Abdominal Surgery and primarily treated with conservative methods trying to induce intestinal peristaltics. As the patient's condition worsened, Hartmann's procedure was performed (sigmoid colon resection). Postoperative recovery was successful and after nine months we established colon continuity. The patient reports for check-ups without any difficulty in defecation. PMID- 20359155 TI - [Influence of manual therapy of cervical spine on typical trigeminal neuralgia: a case report]. AB - This article presents the case of a 43-year-old female patient with pain in the cervical spine area and a typical trigeminal neuralgia (TN; French name "tic douloureux") in the receptive field of the second and the third branches of the left trigeminal nerve. The patient came to our medical practice for a manual therapy of the cervical spine as the application of the standard therapy had not given her any pain reduction in the cervical spine area. As the result of the manual therapy of the cervical spine (nonspecific traction mobilization, specific or segmental mobilization, manipulation), not only a significant pain reduction in the cervical spine area occurred but also a complete cessation of TN. Before manual treatment, and in spite of antiepileptic drugs therapy and acupuncture, the patient had suffered from everyday typical TN attacks. The cessation of typical TN after manual therapy of cervical spine suggests a conclusion that the painful stimuli from the cervical spine structures can be manifested not only as atypical facial pain and/or a cervicogenic headache, but also as a typical TN (painful stimuli from the cervical spine structures-->trigeminocervical nuclei- >convergence of the painful stimuli-->referred pain in the receptive field of the trigeminal nerve-->typical or atypical TN and/or cervicogenic headache). PMID- 20359156 TI - [Hypothermia after cardiac arrest--underused method that saves lives]. AB - Cardiorespiratory arrest causes ischemia and lesion of all organ systems, but the central nervous system is the most vulnerable. It is known that only few minutes of hypoperfusion and ischemia can cause irreversible damage to the brain which is the major frustration of reanimatology. Results of clinical trials suggest positive effects of hypothermia on survival and neurological recovery which led to including this method to Guidelines for resuscitation as a recommended standard method in post-resuscitation period for patients who have not regained consciousness. Methods for induction and maintenance of hypothermia are numerous and various, basically divided into invasive and non-invasive, each with its own advantages and disadvantages which are described in this paper. Despite recognised positive effects of mild therapeutic hypothermia after resuscitation from cardiac arrest, the method is not fully implemented as a standard method in post-resuscitation period. PMID- 20359157 TI - [The role of bcl-2 family proteins in psoriasis]. AB - Apoptosis is a physiological process of programmed cell death responsible for homeostasis in the body. In skin, apoptotic process regulates keratinocyte proliferation and differentiation in that way maintaining homeostasis of epidermal compartment. The process of apoptosis is controlled by proteins of the Bcl-2 family, several proapoptotic (Bax, Bak, Bad) and antiapoptotic (Bcl-2, Bcl x(L)) proteins. Nowadays, it seems that dysfunctional apoptosis has an important role in the pathogenesis of several skin diseases. Psoriasis is a chronic hypeproliferative inflammatory skin disease characterized by abnormal keratinocyte hyperproliferation and differentiation as well as by decreased keratinocyte apoptosis. Based on recent studies, it is likely that apoptosis has an important role in epidermal hyperproliferation of psoriatic lesion. Having in mind the significance of Bcl-2 family proteins in apoptosis, it is important to elucidate their role in psoriasis pathogenesis. Observed upregulation of antiapoptotic and downregulation of proapoptotic Bcl-2 family molecules in psoriatic skin implies their significance in psoriasis development. PMID- 20359158 TI - [Molecular basis of breast cancer related to BRCA 1 and BRCA2 genes: characteristics and targeting therapy]. AB - Breast cancer is one of the most frequent tumors in women, and BRCA1 and BRCA2 genes play a major role in the hereditary susceptibility for this disease. Until the age of 70 women carrying a mutation in BRCA1 or BRCA2 gene have a 45-85% probability of developing breast cancer, and 11-62% probability of developing ovarian cancer. Mutation carrier's tumors contain nonfunctional BRCA1 or BRCA2 genes, which in healthy cells are involved in DNA repair. These tumors show an increased sensitivity to DNA damaging chemical agents and to PARP (poly(adenosine diphosphate-ribose) polymerase1) inhibitors. New targeted therapies already in use are directed toward tumors of mutation carriers. Successful treatment is most likely to be achieved through cooperation of a pathologist, oncologist and a genetic laboratory performing BRCA genes mutation screening. PMID- 20359159 TI - [The organization of mental health care in community]. AB - Integration of the psychiatry in primary care is beneficial for the early detection of mental disorder, better outcome of mental disorder and reduction of stigma. Psychiatry is a leading profession in organisation of mental health services. General practitioners (GPs) in Europe deal with mental disorders in their everyday practice, so the same is expected in Croatia. Graduate and postgraduate education of our GPs is insufficient for this new role. The paper compares actual situation in Croatia with forthcoming needs. The paper suggests that community psychiatry, anti-stigma program, continuing medical education of GPs and network of consultant psychiatrists give the best results in the early detection and treatment of mental disorder. PMID- 20359160 TI - [Croatian Medical Association in the period of transition 1989-1997]. AB - By reviewing the minutes of the 56 sessions of the Presidency and thereafter of the Management council of the Croatian Medical Association, the minutes of annual conventions and other relevant publications, the events in the Croatian Medical Association in the first period of social and market transition, from the first democratic elections in the country up to the beginning of the year 1997 are presented. The construction of the Association before transition, its changes in the statutes during the first three years are demonstrated: the Association restores its old and previous denominations, the professional sections convert to professional societies, the secret elections for all leading places in the organization are introduced. One after another are presented the appeals, meetings and symposia that were sent or held in the headquarter at a time of aggression against Croatia with an aim to ask international help in the defense of the homeland. The conflict between the president of the Association and the Ministry of health and social affairs is presented, as well as the introducing of the Association and its societies in international organizations, the establishing of new scientific/professional societies, the founding of the Commission for human rights and medical ethics, the Norwegian initiative for conciliation of conflicted parties during the war, the non-held 9th and the held 10th Congress of Croatian physicians in Zadar. The list of succumbed Croatian physicians during war is presented. The Association's activity in establishing the Croatian Medical Chamber and thereafter the encounter Association-Chamber is presented as well. The review ends by demonstration of less pronounced activities and by efforts to provide money necessary for renovation ofAssociation's building. Separately the names of colleagues who actively participated in often dramatic moments of transition are mentioned. PMID- 20359161 TI - [Antibiotic prophylaxis of infective endocarditis in patients with moderate risk- rationale for and against]. PMID- 20359162 TI - [Medicolegal excuses for indicating unnecessary diagnostic tests]. PMID- 20359163 TI - [On (internal) propedeutics]. PMID- 20359164 TI - Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. AB - It is well recognized that capsaicin increases thermogenesis through enhancement of catecholamine secretion from the adrenal medulla. In the present study of the antiobesity effect of capsaicin, rats (5-week old) received capsaicin (10 mg/kg) along with a high-fat diet (HFD). In comparison with saline-treated rats, body weight of those in the capsaicin-treated group decreased by 8%. We performed differential proteomic analysis using two-dimensional electrophoresis (2-DE) combined with MALDI-TOF mass spectrometry to elucidate the molecular action of capsaicin on the antiobesity effect in epididymal white adipose tissue (WAT). Protein mapping of WAT homogenates using 2-DE revealed significant alterations to a number of proteins: 10 spots were significantly up-regulated and 10 spots were remarkably down-regulated in HFD fed rats treated with capsaicin. Among them, significant down-regulation of heat shock protein 27 (Hsp27) and Steap3 protein, as well as up-regulation of olfactory receptor (Olr1434) in obese WAT was reported for the first time in association with obesity. Most of the identified proteins are associated with lipid metabolism and redox regulation, in which levels of vimentin, peroxiredoxin, and NAD(P)H:quinone oxidoreductase 1 (NQO1) were significantly reduced (>2-fold), whereas aldo-keto reductase, flavoprotein increased with capsaicin treatment. These data demonstrate that thermogenesis and lipid metabolism related proteins were markedly altered upon capsaicin treatment in WAT, suggesting that capsaicin may be a useful phytochemical for attenuation of obesity. PMID- 20359165 TI - Secretome analysis of human BMSCs and identification of SMOC1 as an important ECM protein in osteoblast differentiation. AB - Extracellular matrix proteins have been implicated in the regulation of osteoblast differentiation of bone marrow derived mesenchymal stem cells (BMSCs) through paracrine or autocrine mechanisms. In the current study, we analyzed the secretory protein profiles of BMSCs grown in osteogenic medium (OSM) and identified SPARC-related modular calcium-binding protein 1 (SMOC1), a member of the SPARC family, as a regulator of osteoblast differentiation of BMSCs. BMSCs with high and low osteogenic potential were grouped and stimulated with OSM, after which conditioned medium was collected and analyzed by LC-MS/MS. We identified 410 proteins, 64 of which were selectively secreted by high osteogenic potential BMSCs. Of these 64 secreted proteins, we selected extracellular matrix proteins for validation in BMSCs undergoing osteoblast differentiation and found that SMOC1 is highly expressed and secreted in BMSCs stimulated with OSM. To examine the role of SMOC1 in osteoblast differentiation, we analyzed the effect of SMOC1 knockdown and overexpression using shRNAs and wild-type cDNA, respectively. Knockdown of SMOC1 significantly inhibited mineralization and the expression of osteoblast differentiation markers, while overexpression of SMOC1 substantially increased the expression of osteoblast differentiation-related genes. Thus, validation of secretome profiling data identified SMOC1 as a putative regulator of osteoblast differentiation of BMSCs. PMID- 20359166 TI - Combined comparative and chemical proteomics on the mechanisms of levo tetrahydropalmatine-induced antinociception in the formalin test. AB - This study investigated the mechanisms involved in the antinociceptive action induced by levo-tetrahydropalmatine (l-THP) in the formalin test by combined comparative and chemical proteomics. Rats were pretreated with l-THP by the oral route (40 mg/kg) 1 h before formalin injection. The antinociceptive effect of l THP was shown in the first and second phases of the formalin test. To address the mechanisms by which l-THP inhibits formalin-induced nociception in rats, the combined comparative and chemical proteomics were applied. A novel high throughput comparative proteomic approach based on 2D-nano-LC-MS/MS was applied to simultaneously evaluate the deregulated proteins involved in the response of l THP treatment in formalin-induced pain rats. Thousands of proteins were identified, among which 17 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (Neurabin-1 and Calcium-dependent secretion activator 1) were randomly selected, and their expression levels were further confirmed by Western Blots. The results matched well with those of proteomics. In the present study, we also described the development and application of l-THP immobilized beads to bind the targets. Following incubation with cellular lysates, the proteome interacting with the fixed l-THP was identified. The results of comparative and chemical proteomics were quite complementary. Although the precise roles of these identified moleculars in l-THP-induced antinociception need further study, the combined results indicated that proteins associated with signal transduction, vesicular trafficking and neurotransmitter release, energy metabolism, and ion transport play important roles in l-THP-induced antinociception in the formalin test. PMID- 20359167 TI - Proteomic profiling of perturbed protein sulfenation in renal medulla of the spontaneously hypertensive rat. AB - Protein sulfenic acids have been proposed as potential biochemical switches for redox signaling. This post-translational modification (PTM) is readily reversible, in contrast to some other types of oxidative PTM. Enhanced oxidative stress has been reported as a feature of hypertension, and renal function has been implicated in the development and progression of the disease in animal models such as the spontaneously hypertensive rat (SHR). However, reactive oxygen species (ROS) are also signaling molecules and may play a role in vascular function. To investigate protein sulfenation under hypertensive conditions, we examined protein extracts of SHR kidney medulla in comparison to medulla from normotensive Wistar rats. Total free thiol content of the SHR medulla was significantly lower than that of Wistar medulla, indicating enhanced oxidation of sulfhydryls. Protein sulfenation was also significantly greater in the medulla of hypertensive animals. Thioredoxin reductase activity was also reduced in SHR medulla and this may account, in part, for enhanced protein sulfenation. Purification of sulfenated proteins from SHR medulla revealed several proteins involved in processes such as metabolism, antioxidant defense, and regulation of nitric oxide synthase. Enhanced sulfenation may represent perturbed redox signaling in SHR medulla, or simply enhanced ROS generation. PMID- 20359168 TI - Lensfree holographic imaging of antibody microarrays for high-throughput detection of leukocyte numbers and function. AB - Characterization of leukocytes is an integral part of blood analysis and blood based diagnostics. In the present paper, we combine lensless holographic imaging with antibody microarrays for rapid and multiparametric analysis of leukocytes from human blood. Monoclonal antibodies (Abs) specific for leukocyte surface antigens (CD4 and CD8) and cytokines (TNF-alpha, IFN-gamma, IL-2) were printed in an array so as to juxtapose cell capture and cytokine detection antibody (Ab) spots. Integration of Ab microarrays into a microfluidic flow chamber (4 muL volume) followed by incubation with human blood resulted in capture of CD4 and CD8 T-cells on specific Ab spots. On-chip mitogenic activation of these cells induced release of cytokine molecules that were subsequently captured on neighboring anticytokine Ab spots. The binding of IL-2, TNF-alpha, and IFN-gamma molecules on their respective Ab spots was detected using horseradish peroxidase (HRP)-labeled anticytokine Abs and a visible color reagent. Lensfree holographic imaging was then used to rapidly ( approximately 4 s) enumerate CD4 and CD8 T lymphocytes captured on Ab spots and to quantify the cytokine signal emanating from IL-2, TNF-alpha, and IFN-gamma spots on the same chip. To demonstrate the utility of our approach for infectious disease monitoring, blood samples of healthy volunteers and human immunodeficiency virus (HIV)-infected patients were analyzed to determine the CD4/CD8 ratio, an important HIV/AIDS diagnostic marker. The ratio obtained by lensfree on-chip imaging of CD4 and CD8 T-cells captured on Ab spots was in close agreement with conventional microscopy-based cell counting. The present paper, describing tandem use of Ab microarrays and lensfree holographic imaging, paves the way for future development of miniature cytometry devices for multiparametric blood analysis at the point of care or in a resource limited setting. PMID- 20359169 TI - Reducing sugar: new functional molecules for the green synthesis of graphene nanosheets. AB - In this paper, we developed a green and facile approach to the synthesis of chemically converted graphene nanosheets (GNS) based on reducing sugars, such as glucose, fructose and sucrose using exfoliated graphite oxide (GO) as precursor. The obtained GNS is characterized with atomic force microscopy, UV-visible absorption spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and so on. The merit of this method is that both the reducing agents themselves and the oxidized products are environmentally friendly. It should be noted that, besides the mild reduction capability to GO, the oxidized products of reducing sugars could also play an important role as a capping reagent in stabilizing as-prepared GNS simultaneously, which exhibited good stability in water. This approach can open up the new possibility for preparing GNS in large-scale production alternatively. Moreover, it is found that GNS-based materials could be of great value for applications in various fields, such as good electrocatalytic activity toward catecholamines (dopamine, epinephrine, and norepinephrine). PMID- 20359170 TI - Copper-catalyzed enantioselective 1,4-addition to alpha,beta-unsaturated aldehydes. AB - The first asymmetric Cu-catalyzed conjugate addition of dialkylzinc zinc reagents to a large scope of enals in presence of phosphoramidite, SimplePhos, or (R) BINAP ligands with enantiomeric excesses up to 90% is reported. Moreover, ACA of Grignard reagents afforded moderate to good 1,4-regioselectivities with enantioselectivities up to 90%. PMID- 20359171 TI - Oxidative amidation and azidation of aldehydes by NHC catalysis. AB - N-heterocyclic carbene catalyzed oxidative amidations of various aldehydes to the corresponding hexafluoroisopropylesters by using the readily available organic oxidant A are described. The hexafluoroisopropylesters prepared in situ are shown to be highly useful active esters for amide bond formation. In addition, oxidative azidation of aldehydes is presented. These mild organocatalytic processes do not use any transition metal. PMID- 20359172 TI - Enantioselective alpha-amination of 1,3-dicarbonyl compounds using squaramide derivatives as hydrogen bonding catalysts. AB - Catalytic enantioselective alpha-hydrazination of 1,3-dicarbonyl compounds with azodicarboxylates was investigated in the presence of our newly developed hydrogen bonding catalyst, squaramide 3j. High yields and high enantioselectivities were achieved with low catalyst loading under mild conditions. PMID- 20359173 TI - Acetylation of chitin nanofibers and their transparent nanocomposite films. AB - Chitin nanofibers were acetylated to modify the fiber surface and were characterized in detail. The acetyl DS could be controlled from 0.99 to 2.96 by changing the reaction time. FT-IR spectra indicate that chitin nanofibers were acetylated completely after 50 min reaction time. X-ray diffraction profiles and TGA curves show that the chitin nanofibers were acetylated heterogeneously from the surface to the core. SEM images show that fiber shape was maintained even in the high-DS sample and that the thickness of the nanofibers increased with the introduction of bulky acetyl groups. Acetylated chitin nanofiber composites were fabricated with acrylic resin with the fiber content of approximately 25 wt %. Due to the size effect, all nanocomposites had high transparency, despite the variety of acetyl DS, and the transparency of the chitin nanofiber composite was less sensitive to acetylation. By only 1 min acetylation, the moisture absorption of the nanocomposite drastically decreased from 4.0 to 2.2%. Although the coefficient of thermal expansion (CTE) of the tricyclodecane dimethanol dimethacrylate (TCDDMA) resin was 6.4 x 10(-5) degrees C(-1), the CTE of the chitin nanofiber/TCDDMA composite decreased to 2.3 x 10(-5) degrees C(-1) by the reinforcement effect of the chitin nanofibers with low thermal expansion. PMID- 20359177 TI - Effect of solvent composition on transformation of micelles to vesicles of rod coil poly(n-hexyl isocyanate-block-2-vinylpyridine) diblock copolymers. AB - The self-aggregation behavior of an amphiphilic rod-coil block copolymer of poly(n-hexyl isocyanate-block-2-vinylpyridine) (PHIC(189)-b-P2VP(228)) (f(P2VP) = 0.78, M(n) = 24.5K) in a tetrahydrofuran (THF)/water system was examined using dynamic light scattering (DLS), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM). The presence of a certain amount of water in the THF-based polymer solution induced a morphological transition from spherical solid micelles to open mouth platelike vesicles. The size of the aggregates increased with an increase in water content in the mixed solvent of THF/water. In the range of 30-40% water, the polymer formed vesicles with an interdigitated architecture of poly(n-hexyl isocyanate) (PHIC) at the center of the membrane and with the poly(2-vinylpyridine) (P2VP) block forming the outer layers and pointing toward the solvent. However, at higher water contents, the thickness of the bilayer increased due to the rearrangement of the vesicle membrane from a flip-flop to a lamellar architecture. After the degradation of the PHIC from the vesicles at basic pH, hollow spherical aggregates remained stable. After removing the THF from the mixed solvent using dialysis, large-sized compound vesicles were formed. PMID- 20359175 TI - Is vanadate reduced by thiols under biological conditions? Changing the redox potential of V(V)/V(IV) by complexation in aqueous solution. AB - Although dogma states that vanadate is readily reduced by glutathione, cysteine, and other thiols, there are several examples documenting that vanadium(V)-sulfur complexes can form and be observed. This conundrum has impacted life scientists for more than two decades. Investigation of this problem requires an understanding of both the complexes that form from vanadium(IV) and (V) and a representative thiol in aqueous solution. The reactions of vanadate and hydrated vanadyl cation with 2-mercaptoethanol have been investigated using multinuclear NMR, electron paramagnetic resonance (EPR), and UV-vis spectroscopy. Vanadate forms a stable complex of 2:2 stoichiometry with 2-mercaptoethanol at neutral and alkaline pH. In contrast, vanadate can oxidize 2-mercaptoethanol; this process is favored at low pH and high solute concentrations. The complex that forms between aqueous vanadium(IV) and 2-mercaptoethanol has a 1:2 stoichiometry and can be observed at high pH and high 2-mercaptoethanol concentration. The solution structures have been deduced based on coordination induced chemical shifts and speciation diagrams prepared. This work demonstrates that both vanadium(IV) and (V)-thiol complexes form and that redox chemistry also takes place. Whether reduction of vanadate takes place is governed by a combination of parameters: pH, solute- and vanadate-concentrations and the presence of other complexing ligands. On the basis of these results it is now possible to understand the distribution of vanadium in oxidation states (IV) and (V) in the presence of glutathione, cysteine, and other thiols and begin to evaluate the forms of the vanadium compounds that exert a particular biological effect including the insulin enhancing agents, antiamoebic agents, and interactions with vanadium binding proteins. PMID- 20359178 TI - Amphiphilic surface active triblock copolymers with mixed hydrophobic and hydrophilic side chains for tuned marine fouling-release properties. AB - Two series of amphiphilic triblock surface active block copolymers (SABCs) were prepared through chemical modification of two polystyrene-block-poly(ethylene-ran butylene)-block-polyisoprene ABC triblock copolymer precursors. The methyl ether of poly(ethylene glycol) [M(n) approximately 550 g/mol (PEG550)] and a semifluorinated alcohol (CF(3)(CF(2))(9)(CH(2))(10)OH) [F10H10] were attached at different molar ratios to impart both hydrophobic and hydrophilic groups to the isoprene segment. Coatings on glass slides consisting of a thin layer of the amphiphilic SABC deposited on a thicker layer of an ABA polystyrene-block poly(ethylene-ran-butylene)-block-polystyrene thermoplastic elastomer were prepared for biofouling assays with algae. Dynamic water contact angle analysis, X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) measurements were utilized to characterize the surfaces. Clear differences in surface structure were realized as the composition of attached side chains was varied. In biofouling assays, the settlement (attachment) of zoospores of the green alga Ulva was higher for surfaces incorporating a large proportion of the hydrophobic F10H10 side chains, while surfaces with a large proportion of the PEG550 side chains inhibited settlement. The trend in attachment strength of sporelings (young plants) of Ulva did not show such an obvious pattern. However, amphiphilic SABCs incorporating a mixture of PEG550 and F10H10 side chains performed the best. The number of cells of the diatom Navicula attached after exposure to flow decreased as the content of PEG550 to F10H10 side chains increased. PMID- 20359179 TI - Electrokinetic vortices and traveling waves in nondilute colloidal dispersions. AB - We report a diverse set of coherent fluid flow instabilities, particle patterns, and traveling waves that develop when an ac electric field is applied to nondilute colloidal dispersions with volume fractions that span 3 orders of magnitude. Novel observed phenomena include the following: vortices with steady and unsteady axes of rotation, unsteady time evolution of vortices formation and vortex merging, as well as traveling waves that propagate through the dispersion. Vortical flows are influenced by strong interactions between particle electrical dipoles as well as electric body forces due to electric fields coupled with gradients in particle volume fraction. We use a 1D Burgers equation to predict the existence of traveling waves in colloidal dispersions. PMID- 20359180 TI - Plasmonic nanorods provide reversible control over nanostructure of self assembled drug delivery materials. AB - The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate of release of incorporated agents from the material, such as drug molecules, and reversible transition between different nanostructures essentially provides an "on-off" switch for release (Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218-226). In this study, the incorporation of plasmonic hydrophobized gold nanorods (GNRs) permits reversible manipulation of nanostructure on-demand, by irradiation of the matrix using a near-infrared laser. Synchrotron small-angle X-ray scattering was used to probe the kinetics of the response of nanostructure to laser irradiation, and the specificity of the approach is shown by the lack of response in the absence of nanorods, or for GNR whose dimensions are not matched to the specific wavelength of the incident light. PMID- 20359181 TI - Rapid and sensitive biomolecular screening with encoded macroporous hydrogel photonic beads. AB - We present a new method to prepare inverse opaline photonic beads with good spherical shape and superior optical performance by simply introducing an interfacial tension system into a template replication method. When the scaffolds of these beads were composed of poly(ethylene glycol) diacrylate hydrogel, they could provide a homogeneous water surrounding, which remedied many shortcomings of biomolecular microcarriers introduced by the presence of the solid surface of them. The suspension array, which used these macroporous hydrogel photonic beads as coding elements, showed obvious advantages in multiplexed capability, rapid biomolecular screening (within 12 min), and highly sensitive detection (with limit of detection of approximately 10(-12) M). PMID- 20359182 TI - Polyphosphazenes as tunable and recyclable supports to immobilize alcohol dehydrogenases and lipases: synthesis, catalytic activity, and recycling efficiency. AB - The polyphosphazene {NP[O(2)C(12)H(7.5)(NH(2))(0.5)]}(n), prepared by reacting {NP[O(2)C(12)H(7.5)(NO(2))(0.5)]} with the Lalancette's reagent, was used for attaching enzymes such as alcohol dehydrogenase (ADH-A) and lipase (CAL-B). The resulting new biocatalysts exhibited great potential as tunable supports for enzymatic reactions in both aqueous and organic media. The material with immobilized ADH-A was as efficient as the commercial enzyme to perform stereoselective bioreductions of ketones in aqueous solutions and could be used for the reduction of various aliphatic and aromatic ketones up to 60 degrees C and recycled several times without significant loss of activity even after three months of storage. The biocatalyst obtained with CAL-B was more efficient than the free enzyme for kinetic resolutions in organic solvents and exhibited a moderately good capability of reutilization. PMID- 20359183 TI - Stereospecific octahedral group 4 bis(phenolate) ether complexes for olefin polymerization. AB - Octahedral group 4 bisphenolate ether complexes, activated by methylaluminoxane, are highly active and stereospecific alpha-olefin polymerization catalysts. X-ray crystallographic analysis reveals the Zr and Hf complexes to be closely isostructural; the bond lengths of the Hf complex are slightly shorter, but the maximum deviation is only 0.062 A. Despite the structural similarity of the Hf and Zr complexes, the Hf complexes generate more highly stereoselective catalysts. In addition to the influence of the transition metal, the structure of the ligand has a large influence on the stereospecificity. Bis-tert-butyl phenyl substituted complexes of Hf and Zr, when activated by MAO at 50-80 degrees C, generate high molecular weight polypropylene (M(n) = 130,000-360,000 g/mol) with isotacticities [mmmm] > 97% and melting points as high as 165 degrees C. PMID- 20359184 TI - Pd(II)-catalyzed hydroxyl-directed C-H olefination enabled by monoprotected amino acid ligands. AB - A novel Pd(II)-catalyzed ortho-C-H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle. PMID- 20359185 TI - Kinetic and inhibition studies of dihydroxybenzoate-AMP ligase from Escherichia coli. AB - Inhibition of siderophore biosynthetic pathways in pathogenic bacteria represents a promising strategy for antibacterial drug development. Escherichia coli synthesize and secrete the small molecule iron chelator siderophore, enterobactin, in response to intracellular iron depletion. Here we describe a detailed kinetic analysis of EntE, one of six enzymes in the enterobactin synthetase gene cluster. EntE catalyzes the ATP-dependent condensation of 2,3 dihydroxybenzoic acid (DHB) and phosphopantetheinylated EntB (holo-EntB) to form covalently arylated EntB, a product that is vital for the final assembly of enterobactin. Initial velocity studies show that EntE proceeds via a bi-uni-uni bi ping-pong kinetic mechanism with a k(cat) equal to 2.8 s(-1) and K(m) values of 2.5, 430, and 2.9 microM for DHB, ATP, and holo-EntB-ArCP, respectively. Inhibition and direct binding experiments suggest that, during the first half reaction (adenylation), DHB binds first to the free enzyme, followed by ATP and the release of pyrophosphate to form the adenylate intermediate. During the second half-reaction (ligation), phosphopantetheinylated EntB binds to the enzyme followed by the release of products, AMP and arylated EntB. Two hydrolytically stable adenylate analogues, 5'-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) and 5' O-[N-(2,3-dihydroxybenzoyl)sulfamoyl]adenosine (DHB-AMS), are shown to act as slow-onset tight-binding inhibitors of the enzyme with (app)K(i) values of 0.9 and 3.8 nM, respectively. Direct binding experiments, via isothermal titration calorimetry, reveal low picomolar dissociation constants for both analogues with respect to EntE. The tight binding of Sal-AMS and DHB-AMS to EntE suggests that these compounds may be developed further as effective antibiotics targeted to this enzyme. PMID- 20359186 TI - Gastroprotective effect of carnosic acid gamma-lactone derivatives. AB - Carnosic acid (1) has been shown to possess gastroprotective activity in vitro and in vivo. However, little is known of the gastroprotective effect or cytotoxicity of carnosic acid gamma-lactone (3). To determine structure-activity relationships, a series of 17 esters of 3 were prepared including aliphatic, aromatic, and heterocyclic derivatives. Also, two units of 3 were coupled with succinic and phthalic acid as linkers. The compounds were assessed for their gastroprotective effect in the HCl/EtOH-induced gastric lesions model in mice and for cytotoxicity in human lung fibroblasts, human adenocarcinoma AGS cells, and Hep G2 hepatocellular carcinoma cells. At a single oral dose of 40 mg/kg, the gastroprotective effect increased moderately with the length of the alkyl chain. The best effects were observed for the butyrate (9) and chloroacetate (6) derivatives. Activity of fatty acid esters increased with chain length but decreased with unsaturation. The best gastroprotective effect, with lowest cytotoxicity, was found for the palmitate (11) and oleate (12) derivatives. PMID- 20359187 TI - Highly selective hydroiodation of alkynes using an iodine-hydrophosphine binary system. AB - A novel hydroiodation of alkynes (1) using an iodine/hydrophosphine binary system takes place regioselectively to provide the corresponding Markovnikov-type adducts (2) in good yield. This hydroiodation is advantageous in terms of mild conditions, convenient operation, and tolerance to various functional groups. PMID- 20359188 TI - Synthesis of monodisperse TiO2-paraffin core-shell nanoparticles for improved dielectric properties. AB - Core-shell structures of oxide nanoparticles having a high dielectric constant, and organic shells with large breakdown field are attractive candidates for large electrical energy storage applications. A high growth temperature, however, is required to obtain the dielectric oxide nanoparticles, which affects the process of core-shell formation and also leads to poor control of size, shape, and size distribution. In this communication, we report a new synthetic process to grow core-shell nanoparticles by means of an experimental method that can be easily adapted to synthesize core-shell structures from a variety of inorganic-organic or inorganic-inorganic materials. Monodisperse and spherical TiO2 nanoparticles were produced at room temperature as a collimated cluster beam in the gas phase using a cluster-deposition source and subsequently coated with uniform paraffin nanoshells using in situ thermal evaporation, prior to deposition on substrates for further characterization and device processing. The paraffin nanoshells prevent the TiO2 nanoparticles from contacting each other and also act as a matrix in which the volume fraction of TiO2 nanoparticles was varied by controlling the thickness of the nanoshells. Parallel-plate capacitors were fabricated using dielectric core-shell nanoparticles having different shell thicknesses. With respect to the bulk paraffin, the effective dielectric constant of TiO2-paraffin core-shell nanoparticles is greatly enhanced with a decrease in the shell thickness. The capacitors show a minimum dielectric dispersion and low dielectric losses in the frequency range of 100 Hz-1 MHz, which are highly desirable for exploiting these core-shell nanoparticles for potential applications. PMID- 20359189 TI - Solution-processed squaraine bulk heterojunction photovoltaic cells. AB - The donor, 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl] squaraine (SQ) is used with the acceptor, [6,6]-phenyl C70 butyric acid methyl ester (PC70BM) to result in efficient, solution-processed, small-molecule bulk heterojunction photovoltaic cells. The distribution of the donor nanoparticles in the acceptor matrix as a function of relative concentrations results in a trade-off between exciton dissociation and hole mobility (and hence, cell series resistance). A bulk heterojunction solar cell consisting of an active region with a component ratio of SQ to PC70BM of 1:6 has a power conversion efficiency of 2.7 +/- 0.1% with a 8.85 +/- 0.22 mA/cm(2) short-circuit current density and an open-circuit voltage of 0.89 +/- 0.01 V obtained under simulated 1 sun (100 mW/cm(2)) air mass 1.5 global (AM1.5 G) solar illumination. This is a decrease from 3.3 +/- 0.3% at 0.2 sun intensity, and is less than that of a control planar heterojunction SQ/C60 cell with 4.1 +/- 0.2% at 1 sun, suggesting that the nanoparticle morphology introduces internal resistance into the solution-based thin film. The nanomorphology and hole mobility in the films is strongly dependent on the SQ-to PC70BM ratio, increasing by greater than 2 orders of magnitude as the ratio increases from 28% to 100% SQ. PMID- 20359190 TI - Self-assembly of CdTe tetrapods into network monolayers at the air/water interface. AB - Cadmium telluride (CdTe) tetrapods are synthesized with varying aspect ratios through multiple injections of the Te precursor, which provides an excellent means of controlling and tailoring the optical properties of the tetrapods. The self-assembly of CdTe tetrapods at the air/water interface is explored using the Langmuir-Blodgett (LB) technique due to potential use in solar cells arising from the intriguing tetrapod shape that improves charge transport and the optimum band gap energy of CdTe that enhances light absorption. Interestingly, the Langmuir isotherm shows two pressure plateau regions: one at approximately 10 mN/m with the other at the high surface pressure of approximately 39 mN/m. LB deposition at various pressures allows the discernment of the unique two-dimensional packing alluded in the isotherm. By placing CdTe at the air/water interface, it is revealed in the deposition that the tetrapods experienced a dewetting phenomenon, forming a ribbon structure at the onset of surface pressure with a height corresponding to the length of one tetrapod arm. With the increase of surface pressure, the ribbons widen to an eventual large-scale percolated network pattern. The packing density of tetrapods is successfully manipulated by controlling the surface pressure, which may find promising applications in optoelectronic devices. PMID- 20359191 TI - Transition states of uncatalyzed hydrolysis and aminolysis reactions of a ribosomal P-site substrate determined by kinetic isotope effects. AB - The ester bond of peptidyl-tRNA undergoes nucleophilic attack in solution and when catalyzed by the ribosome. To characterize the uncatalyzed hydrolysis reaction, a model of peptide release, the transition state structure for hydrolysis of a peptidyl-tRNA mimic was determined. Kinetic isotope effects were measured at several atoms that potentially undergo a change in bonding in the transition state. Large kinetic isotope effects of carbonyl (18)O and alpha deuterium substitutions on uncatalyzed hydrolysis indicate the transition state is nearly tetrahedral. Kinetic isotope effects were also measured for aminolysis by hydroxylamine to study a reaction similar to the formation of a peptide bond. In contrast to hydrolysis, the large leaving group (18)O isotope effect indicates the C-O3' bond has undergone significant scission in the transition state. The smaller carbonyl (18)O and alpha-deuterium effects are consistent with a later transition state. The assay developed here can also be used to measure isotope effects for the ribosome-catalyzed reactions. These uncatalyzed reactions serve as a basis for determining what aspects of the transition states are stabilized by the ribosome to achieve a rate enhancement. PMID- 20359192 TI - Hybrid polymer therapeutics incorporating bioresponsive, coiled coil peptide linkers. AB - This article reports the design, synthesis and results of first in vitro model studies of a conceptually novel class of polymer therapeutics in which the cargo is attached to a polymer backbone via a noncovalent, biologically inspired coiled coil linker, which is formed by heterodimerization of two complementary peptide sequences that are linked to the polymer carrier and the cargo, respectively. In contrast with the polymer-drug conjugates prepared so far, in which the drug is typically attached via an enzymatically or hydrolytically cleavable linker, the noncovalent polymer therapeutics proposed in this article offer several potential advantages, including facile access to combination therapeutics and rapid production of compound libraries to screen for structure-activity relationships. Furthermore, the coiled coil based peptide linkers may not only be useful to bind and release guests but may also play an active role in enhancing and directing intracellular transport and trafficking, which may make these constructs of particular interest for the cytosolic delivery of biomolecular therapeutics. PMID- 20359193 TI - Single-molecule chemistry of metal phthalocyanine on noble metal surfaces. AB - To develop new functional materials and nanoscale electronics, researchers would like to accurately describe and precisely control the quantum state of a single molecule on a surface. Scanning tunneling microscopy (STM), combined with first principles simulations, provides a powerful technique for acquiring this level of understanding. Traditionally, metal phthalocyanine (MPc) molecules, composed of a metal atom surrounded by a ligand ring, have been used as dyes and pigments. Recently, MPc molecules have shown great promise as components of light-emitting diodes, field-effect transistors, photovoltaic cells, and single-molecule devices. In this Account, we describe recent research on the characterization and control of adsorption and electronic states of a single MPc molecule on noble metal surfaces. In general, the electronic and magnetic properties of a MPc molecule largely depend on the type of metal ion within the phthalocyanine ligand and the type of surface on which the molecule is adsorbed. However, with the STM technique, we can use on-site molecular "surgery" to manipulate the structure and the properties of the molecule. For example, STM can induce a dehydrogenation reaction of the MPc, which allows us to control the Kondo effect, which describes the spin polarization of the molecule and its interaction with the complex environment. A specially designed STM tip can allow researchers to detect certain molecule-surface hybrid states that are not accessible by other techniques. By matching the local orbital symmetry of the STM tip and the molecule, we can generate the negative differential resistance effect in the formed molecular junction. This orbital symmetry based mechanism is extremely robust and does not critically depend on the geometry of the STM tip. In summary, this simple model system, a MPc molecule absorbed on a noble metal surface, demonstrates the power of STM for quantum characterization and manipulation of single molecules, highlighting the potential of this technique in a variety of applications. PMID- 20359194 TI - The influence of spin effects on the gas phase reactions of carbanions with N and O atoms. AB - Molecular anions have been recently detected in the denser regions of the interstellar medium. However, the chemical reactions of molecular anions with atomic species that are abundant in the ISM remain largely unexplored. This work is an experimental and computational study of CH(2)CN(-), CH(3)CHCN(-), (CH(3))(2)CCN(-), and CH(2)CHO(-) reacting with N and O atoms. In all cases the reactions of anions with O atoms exhibit larger reaction rate constants compared to the corresponding reactions with N atoms. Our study indicates that spin forbidden reactions are the probable pathways in the reactions with N atoms, whereas spin-allowed reactions are the dominant processes in the reactions with O atoms. The major factor influencing the reaction rate constants of anions with N and O atoms is whether a spin-allowed barrierless pathway exists. The rich chemistry observed in this work provides a greater understanding of the ion-atom reaction processes, as well as some new avenues for further spin chemistry research. PMID- 20359195 TI - Charge dependent substrate activity of C3' and N3 functionalized, organometallic technetium and rhenium-labeled thymidine derivatives toward human thymidine kinase 1. AB - Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for the noninvasive imaging of cancer cell proliferation using radiolabeled thymidine analogues such as [(18)F]3'-fluoro-3'-deoxythymidine ([(18)F]FLT). A thymidine analogue for single photon emission computed tomography (SPECT), which incorporates the readily available and inexpensive nuclide technetium-99m, would be of considerable practical interest. hTK1 is known to accommodate modification of the structure of the natural substrate thymidine at the positions N3 and C3' and, to a lesser extent, C5. In this work, we used the copper-catalyzed azide alkyne cycloaddition to synthesize two series of derivatives in which thymidine is functionalized at either the C3' or N3 position with chelating systems suitable for the M(CO)(3) core (M = (99m)Tc, Re). The click chemistry approach enabled complexes with different structures and overall charges to be synthesized from a common precursor. Using this strategy, the first organometallic hTK1 substrates in which thymidine is modified at the C3' position were identified. Phosphorylation of the organometallic derivatives was measured relative to thymidine. We have shown that the influence of the overall charge of the derivatives is dependent on the position of functionalization. In the case of the C3'-functionalized derivatives, neutral and anionic substrates were most readily phosphorylated (20-28% of the value for the parent ligand thymidine), whereas for the N3-functionalized derivatives, cationic and neutral complexes were apparently better substrates for the enzyme (14-18%) than anionic derivatives (9%). PMID- 20359196 TI - Remodeling of dynamic structures of HIV-1 envelope proteins leads to synthetic antigen molecules inducing neutralizing antibodies. AB - A synthetic antigen targeting membrane-fusion mechanism of HIV-1 has a newly designed template with C3-symmetric linkers mimicking N36 trimeric form. The antiserum produced by immunization of the N36 trimeric form antigen showed structural preference in binding to N36 trimer and stronger inhibitory activity against HIV-1 infection than the N36 monomer. Our results suggest an effective strategy of HIV vaccine design based on a relationship to the native structure of proteins involved in HIV fusion mechanisms. PMID- 20359197 TI - Influence of cation structure on binary liquid-liquid equilibria for systems containing ionic liquids based on trifluoromethanesulfonate anion with hydrocarbons. AB - Binary liquid-liquid equilibria for 15 systems containing an ionic liquid (1 butyl-3-methylimidazolium trifluoromethanesulfonate, 1-butyl-3-methylpyridinium trifluoromethanesulfonate, 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate) with a hydrocarbon (n-hexane, n-heptane, cyclohexane, benzene, toluene) were measured by the dynamic method. The influence of cation structure of trifluoromethanesulfonate anion based ionic liquids on solubility of aliphatic and aromatic hydrocarbons is discussed. PMID- 20359198 TI - Evidence for a bicarbonate "escort" site in Haemophilus influenzae beta-carbonic anhydrase . AB - The Haemophilus influenzae beta-carbonic anhydrase (HICA) allosteric site variants V47A and G41A were overexpressed and purified to homogeneity. These variants have k(cat)/K(m) values similar to that of the wild-type enzyme and exhibit a similar dramatic decrease in catalytic activity at pH <8.0. However, both HICA-G41A and -V47A were serendipitously found to bind sulfate ion or bicarbonate ion near pairs of Glu50 and Arg64 residues located on the dimerization interface. In the case of HICA-V47A, bicarbonate ions simultaneously bind to both the dimerization interface and the allosteric sites. For HICA-G41A, two of 12 chains in the asymmetric unit bind bicarbonate ion exclusively at the dimerization interface, while the remaining 10 chains bind bicarbonate ion exclusively at the allosteric site. We propose that the new anion binding site along the dimerization interface of HICA is an "escort" site that represents an intermediate along the ingress and egress route of bicarbonate ion to and from the allosteric binding site, respectively. The structural evidence for sulfate binding at the escort site suggests that the mechanism of sulfate activation of HICA is the result of sulfate ion competing for bicarbonate at the escort site, preventing passage of bicarbonate from the bulk solution to its allosteric site. PMID- 20359199 TI - Surface modification of cellulose fiber via supramolecular assembly of biodegradable polyesters by the aid of host-guest inclusion complexation. AB - In this article, we report a novel surface modification method for cellulose fiber that is based on supramolecular assembly. Beta-cyclodextrin (beta-CD) was first covalently grafted onto the fiber surface. Then poly(epsilon-caprolactone) (PCL) oligomers having both ends capped with adamantane motifs (i.e., PCL-AD) were immobilized to the cellulose fiber surface through the host-guest inclusion complexation between beta-CD and AD motif. FTIR-ATR and XPS analyses confirmed the successful assembly of PCL-ADs, which was further supported by the increasing trend of weight gain with the concentration of CDs on the fiber surface. Contact angle and TGA measurements reflect the enhanced hydrophobicity and thermal stability of the cellulose fiber as a consequence of this modification. The morphologies of the cellulose fiber before and after the assembly process have also been compared by SEM. PMID- 20359201 TI - Athabasca oil sands process water: characterization by atmospheric pressure photoionization and electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. AB - The Athabasca oil sands in Canada are a less conventional source of oil which have seen rapid development. There are concerns about the environmental impact, with particular respect to components in oil sands process water which may enter the aquatic ecosystem. Naphthenic acids have been previously targeted for study, due to their implications in toxicity toward aquatic wildlife, but it is believed that other components, too, contribute toward the potential toxicity of the oil sands process water. When mass spectrometry is used, it is necessary to use instrumentation with a high resolving power and mass accuracy when studying complex mixtures, but the technique has previously been hindered by the range of compounds that have been accessible via common ionization techniques, such as electrospray ionization. The research described here applied Fourier transform ion cyclotron resonance mass spectrometry in conjunction with electrospray ionization and atmospheric pressure photoionization, in both positive-ion and negative-ion modes, to the characterization of oil sands process water for the first time. The results highlight the need for broader characterization when investigating toxic components within oil sands process water. PMID- 20359200 TI - Approach to interfacial and intramolecular electron transfer of the diheme protein cytochrome c4 assembled on Au(111) surfaces. AB - Intramolecular electron transfer (ET) between metal centers is a core feature of large protein complexes in photosynthesis, respiration, and redox enzyme catalysis. The number of microscopic redox potentials and ET rate constants is, however, prohibitive for experimental cooperative ET mapping, but two-center proteins are simple enough to offer complete communication networks. At the same time, multicenter redox proteins operate in membrane environments where conformational dynamics may lead to gated ET features different from conditions in homogeneous solution. The bacterial respiratory diheme protein Pseudomonas stutzeri cytochrome c(4) has been a target for intramolecular, interheme ET. We report here voltammetric and in situ scanning tunneling microscopy (STM) data for P. stutzeri cyt c(4) at single-crystal, atomically planar Au(111)-electrode surfaces modified by variable-length omega-mercapto-alkanoic carboxylic acids. As evidenced by in situ STM, the strongly dipolar protein is immobilized in a close to vertical orientation at this surface with the positively charged high potential heme domain adjacent to the electrode. This orientation gives asymmetric voltammograms with two one-ET peaks in the cathodic direction and a single two-ET peak in the anodic direction. Intramolecular, interheme ET with high, 8,000-30,000 s(-1), rate constants is notably an essential part of this mechanism. The high rate constants are in striking contrast to ET reactions of P. stutzeri cyt c(4) with small reaction partners in homogeneous solution for which kinetic analysis clearly testifies to electrostatic cooperative effects but no intramolecular, interheme ET higher than 0.1-10 s(-1). This difference suggests a strong gating feature of the process. On the basis of the three-dimensional structure of P. stutzeri cyt c(4), gating is understandable due to the through space, hydrogen-bonded electronic contact between the heme propionates which is highly sensitive to environmental configurational fluctuations. PMID- 20359202 TI - Desulfitative cross-coupling of protecting group-free 2-thiouracil derivatives with organostannanes. AB - We here report a unique and efficient copper bromide mediated pallado-catalyzed coupling of protecting group-free 2-thiouracil derivatives with organostannanes. The nature of the copper appears to be crucial for successful cross coupling. PMID- 20359203 TI - Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source. AB - A simple copper-catalyzed direct amination of ortho-functionalized haloarenes (2 halobenzoic acid, 2-halobenzamide, and N-(2-bromophenyl)acetamide derivatives) has been developed with use of NaN(3) as the amino source in ethanol, and the corresponding ortho-functionalized aromatic amines were synthesized in good to excellent yields. The protocol undergoes one-pot Ullmann-type coupling of ortho functionalized haloarenes with NaN(3) to lead to ortho-functionalized azidoarenes, followed by reduction with ethanol. PMID- 20359204 TI - Gas phase energetics of CN radicals in radio frequency discharges: influence on surface reaction probability during deposition of carbon nitride films. AB - The CN radical has been implicated as an important contributor to the plasma deposition of amorphous carbon nitride. Here, laser-induced fluorescence and optical emission spectroscopy were used to explore in greater detail the gas phase energetics of CN in CH(3)CN, BrCN, and CH(4)/N(2) plasmas. Measurements of CN internal temperatures from these systems yield rotational temperatures well above 300 K, with notably higher ones for CN formed in BrCN plasmas, and vibrational temperatures of 4500-6000 K in all three systems. The data agree with the results of literature photodissociation experiments, and extension of those results to the plasma systems studied here provides insight into both the mechanisms for CN formation as well as the disposal of energy during fragmentation of the parent molecules. The internal energies of these species may influence their surface behavior; this issue is discussed in the context of previous work from our lab as well as others. The apparent trends not only offer a valuable perspective on the chemical dynamics of CN during the plasma deposition of a-CN(x) films but are also suggestive of a more general relationship between the energetics of plasma species and their behavior at surfaces. PMID- 20359205 TI - Electrochemical study of 3-(N-alkylamino)thiophenes: experimental and theoretical insights into a unique mechanism of oxidative polymerization. AB - A number of conjugated polymer systems can be generated via electropolymerization, including polythiophenes and polyanilines. While both have been reported to polymerize anodically via radical coupling, the presence of the aniline nitrogen plays a significant role in the mechanism of electropolymerization. In this study, the electropolymerization mechanism of 3-(N alkylamino)thiophenes, structural hybrids of thiophene and aniline, is studied utilizing experimental and theoretical methods. Synthesis of new short chain 3-(N alkylamino)thiophenes is discussed, and a mechanism of electropolymerization is proposed whereby oxidation occurs through removal of a nitrogen lone pair electron, followed by a chemical step resulting in radical contribution at the 2 position of the thiophene ring. Coupling of these final radical cations thus results in a typical poly(alpha-alpha'-thiophene) backbone. PMID- 20359206 TI - Kinetic isotope effects on the noncovalent flavin mutant protein of pyranose 2 oxidase reveal insights into the flavin reduction mechanism. AB - Pyranose 2-oxidase (P2O) from Trametes multicolor contains a flavin adenine dinucleotide (FAD) cofactor covalently linked to the N(3) atom of His167. The enzyme catalyzes the oxidation of aldopyranoses by molecular oxygen to generate 2 keto-aldoses and H(2)O(2) as products. In this study, the transient kinetics and primary and solvent kinetic isotope effects of the mutant in which His167 has been replaced with Ala (H167A) were investigated, to elucidate the functional role of the 8a-N(3)-histidyl FAD linkage and to gain insights into the reaction mechanism of P2O. The results indicate that the covalent linkage is mainly important for a reductive half-reaction in which the FAD cofactor is reduced by d glucose, while it is not important for an oxidative half-reaction in which oxygen reacts with the reduced FAD to generate H(2)O(2). d-Glucose binds to H167A via multiple binding modes before the formation of the active Michaelis complex, and the rate constant of flavin reduction decreases approximately 22-fold compared to that of the wild-type enzyme. The reduction of H167A using d-glucose isotopes (2 d-d-glucose, 3-d-d-glucose, and 1,2,3,4,5,6,6-d(7)-d-glucose) as substrates indicates that the primary isotope effect results only from substitution at the C2 position, implying that H167A catalyzes the oxidation of d-glucose regiospecifically at this position. No solvent kinetic isotope effect was detected during the reductive half-reaction of the wild-type or H167A enzyme, implying that the deprotonation of the d-glucose C2-OH group may occur readily upon the binding to P2O and is not synchronized with the cleavage of the d glucose C2-H bond. The mutation has no drastic effect on the oxidative half reaction of P2O, as H167A is very similar to the wild-type enzyme with respect to the kinetic constants and the formation of the C4a-hydroperoxyflavin intermediate. Kinetic mechanisms for both half-reactions of H167A were proposed on the basis of transient kinetic data and were verified by kinetic simulations and steady-state kinetic parameters. PMID- 20359207 TI - A computer simulation study on self- and cross-aggregation of multiple polar species in supercritical carbon dioxide. AB - The effect of hydrogen-bond cooperativity on self- and cross-aggregation of multiple polar species in supercritical carbon dioxide was investigated using both ab initio calculations and Monte Carlo simulations. Ab initio calculations indicate that hydrogen-bond cooperativity has a significant impact on the cluster size, but does not greatly influence the composition of clusters. The microscopic structures in the ethanol + CO(2) and acetic acid + CO(2) binary mixtures were first studied using Monte Carlo simulations with a strict set of criteria for hydrogen bonding, and a satisfactory agreement with experimental data was achieved. The state of microscopic phase separation in the ethanol + water + CO(2) and acetic acid + water + CO(2) ternary mixtures was then extensively investigated, indicating that the size and composition of aggregates are strongly dependent on the mixing ratio. Moreover, hydrogen-bond cooperativity must be considered to acquire more thorough understanding of the hydration process. On the basis of the detailed distributions of aggregate size and structure, a new two-staged hydration mechanism was finally proposed for the ternary solutions. PMID- 20359208 TI - Preparation and characterization of self-cleaning glass for vehicle with niobia nanosheets. AB - Self-cleaning glasses were prepared by coating niobia nanosheets and investigated on the performance. The coated glass heated at >450 degrees C had very low turbidity, high hardness, and excellent adhesion properties. Niobia nanosheets ([Nb(3)O(8)](-)) reacted with sodium ions (Na(+)) diffused from the glass into the films to form a crystalline phase of NaNb(3)O(8) and this phase was converted to NaNbO(3) at >450 degrees C. The films exhibited photoinduced hydrophilicity under UV irradiation but low photocatalytic oxidation activity. Excellent self cleaning ability of the niobia nanosheet coated glass was confirmed by the Taber abrasion test, which is thought to be a candidate as self-cleaning glasses for vehicles. PMID- 20359209 TI - Benzothiazole-based fluorophores of donor-pi-acceptor-pi-donor type displaying high two-photon absorption. AB - A series of novel heterocycle-based dyes with donor-pi-bridge-acceptor-pi-bridge donor (D-pi-A-pi-D) structural motif, where benzothiazole serves as an electron withdrawing core, have been designed and synthesized via palladium-catalyzed Sonogashira and Suzuki-type cross-coupling reactions. All the target chromophores show strong one-photon and two-photon excited emission. The maximum two-photon absorption (TPA) cross sections delta(TPA) of the prepared derivatives bearing diphenylamino functionalities occur at wavelengths ranging from 760 to 800 nm and are as large as approximately 900-1100 GM. One- and two-photon absorption characteristics of the title dyes have also been investigated by using density functional theory (DFT) and the structure-property relationships are discussed. The TPA cross sections calculated by means of quadratic response time-dependent DFT using the Coulomb-attenuated CAM-B3LYP functional support the experimentally observed trends within the series, as well as higher delta(TPA) values of the title compounds compared to those of analogous fluorene or carbazole-derived dyes. In contrast, the traditional B3LYP functional was not successful in predicting the observed trend of TPA cross sections for systems with different central cores. In general, structural modification of the pi-bridge composition by replacement of ethynylene (alkyne) with E-ethenylene (alkene) linkages and/or replacement of dialkylamino electron-donating edge substituents by diarylamino ones results in an increase of delta(TPA) values. The combination of large TPA cross sections and high emission quantum yields makes the title benzothiazole based dyes attractive for applications involving two-photon excited fluorescence (TPEF). PMID- 20359210 TI - Surface-initiated polymerization of superhydrophobic polymethylene. AB - We report a new surface-initiated polymerization strategy that yields superhydrophobic polymethylene (PM) films from initially smooth substrates of gold and silicon. The films are prepared by assembling a vinyl-terminated self assembled monolayer, followed by exposure of the surface to a 0.1 M solution of borane, and polymerizing from the borane sites upon exposure to a solution of diazomethane at -17 degrees C. Surface-initiated polymethylenation (SIPM) presents rapid growth in relation to other surface-initiated reactions, producing PM films thicker than 500 nm after 2 min of reaction and 3 microm after 24 h of reaction. AFM and SEM images show the presence of micro- and nanoscale features that enable the entrapment of air when exposed to water. Consistent with this result, these films exhibit advancing water contact angles greater than 160 degrees, dramatically different than 103 degrees measured for smooth PM films, and hysteresis values ranging from 2 degrees to 40 degrees, depending on the substrate and polymerization time. The superhydrophobic character of the films results in the entrapment of air at the polymer/solution interface to provide remarkable resistances greater than 10(10) Omega x cm(2) against the transport of aqueous redox probes and cause the film to behave as a "perfect" capacitor. PMID- 20359212 TI - Multiple nonstoichiometric phases with discrete composition ranges in the CaAu5 CaAu4Bi-BiAu2 system. A case study of the chemistry of spinodal decomposition. AB - Synthetic explorations in the CaAu(5)-CaAu(4)Bi-BiAu(2) system at 400 degrees C reveal five separate solid solution regions that show three distinct substitution patterns in the CaAu(5) parent: (I) CaAu(4)(Au(1-m)Bi(m)) with 0 < or = m < or = 0.15(1), (II) 0.33(1) < or = m < or = 0.64(1), (III) 0.85(4) < or = m < or = 0.90(2); (IV) (Ca(1-r)Au(r))Au(4)(Bi(1-s)Au(s)) with 0 < or = r < or = 0.39(1) and 0 < or = s < or = 0.12(2); (V) (Ca(1-p-q)Au(p)Bi(q))Au(4)Bi with 0.09(2) < or = p < or = 0.13(1) and 0.31(2) < or = q < or = 0.72(4). Single crystal X-ray studies establish that all of these phase regions have common cubic symmetry F43m and that their structures (MgCu(4)Sn-type, an ordered derivative of MgCu(2)) all feature three-dimensional networks of Au(4) tetrahedra, in which the truncated tetrahedra are centered and capped by Ca/Au, Au/Bi, or Ca/Au/Bi mixtures to give 16-atom Friauf polyhedra. TB-LMTO-ASA and -COHP calculations also reveal that direct interactions between Ca-Au and Ca-Bi pairs of atoms are relatively weak and that the Bi-Au interactions in the unstable ideal CaAu(4)Bi are antibonding in character at E(F) but that their bonding is optimized at +/-1 e. Compositions between the five nonstoichiometric phases appear to undergo spinodal decompositions. The last phenomenon has been confirmed by HRTEM, STEM-HAADF, EPMA, and XRD studies of the nominal composition CaAu(4.25)Bi(0.75). Its DTA analyses suggest that the phases resulting from spinodal decomposition have nearly the same melting point (approximately 807 degrees C), as expected, and that they are interconvertible through peritectic reactions at approximately 717 degrees C. PMID- 20359211 TI - p-Nitrophenol degradation via 4-nitrocatechol in Burkholderia sp. SJ98 and cloning of some of the lower pathway genes. AB - Microbial degradation studies have pointed toward the occurrence of two distinct PNP catabolic pathways in Gram positive and Gram negative bacteria. The former involves 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT), and maleylacetate (MA) as major degradation intermediates, whereas the later proceeds via formation of 1,4-benzoquinone (BQ) and hydroquinone (HQ). In the present study we identified a Gram negative organism viz. Burkholderia sp. strain SJ98 that degrades PNP via 4NC, BT, and MA. A 6.89 Kb genomic DNA fragment of strain SJ98 that encompasses seven putatively identified ORFs (orfA, pnpD, pnpC, orfB, orfC, orfD, and orfE) was cloned. PnpC is benzenetriol dioxygenase belonging to the intradiol dioxygenase superfamily, whereas PnpD is identified as maleylacetate reductase, a member of the Fe-ADH superfamily showing NADH dependent reductase activity. The in vitro activity assays carried out with purified pnpC and pnpD (btd and mar) gene products transformed BT to MA and MA to beta-ketoadipate, respectively. The cloning, sequencing, and characterization of these genes along with the functional PNP degradation studies ascertained the involvement of 4-NC, BT, and MA as degradation intermediates of PNP pathway in this strain. This is one of the first conclusive reports for 4-NC and BT mediated degradation of PNP in a Gram negative organism. PMID- 20359213 TI - Effect of stalling after mismatches on the error catastrophe in nonenzymatic nucleic acid replication. AB - The frequency of errors during genome replication limits the amount of functionally important information that can be passed on from generation to generation. During the origin of life, mutation rates are thought to have been quite high, raising a classic chicken-and-egg paradox: could nonenzymatic replication propagate sequences accurately enough to allow for the emergence of heritable function? Here we show that the theoretical limit on genomic information content may increase substantially as a consequence of dramatically slowed polymerization after mismatches. As a result of postmismatch stalling, accurate copies of a template tend to be completed more rapidly than mutant copies and the accurate copies can therefore begin a second round of replication more quickly. To quantify this effect, we characterized an experimental model of nonenzymatic, template-directed nucleic acid polymerization. We found that most mismatches decrease the rate of primer extension by more than 2 orders of magnitude relative to a matched (Watson-Crick) control. A chemical replication system with this property would be able to propagate sequences long enough to have function. Our study suggests that the emergence of functional sequences during the origin of life would be possible even in the face of the high intrinsic error rates of chemical replication. PMID- 20359214 TI - A calix[4]arene strapped calix[4]pyrrole: an ion-pair receptor displaying three different cesium cation recognition modes. AB - An ion-pair receptor, the calix[4]pyrrole-calix[4]arene pseudodimer 2, bearing a strong anion-recognition site but not a weak cation-recognition site, has been synthesized and characterized by standard spectroscopic means and via single crystal X-ray diffraction analysis. In 10% CD(3)OD in CDCl(3) (v/v), this new receptor binds neither the Cs(+) cation nor the F(-) anion when exposed to these species in the presence of other counterions; however, it forms a stable 1:1 solvent-separated CsF complex when exposed to these two ions in concert with one another in this same solvent mixture. In contrast to what is seen in the case of a previously reported crown ether "strapped" calixarene-calixpyrrole ion-pair receptor 1 (J. Am. Chem. Soc. 2008, 130, 13162-13166), where Cs(+) cation recognition takes place within the crown, in 2.CsF cation recognition takes place within the receptor cavity itself, as inferred from both single-crystal X-ray diffraction analyses and (1)H NMR spectroscopic studies. This binding mode is supported by calculations carried out using the MMFF94 force field model. In 10% CD(3)OD in CDCl(3) (v/v), receptor 2 shows selectivity for CsF over the Cs(+) salts of Cl(-), Br(-), and NO(3)(-) but will bind these other cesium salts in the absence of fluoride, both in solution and in the solid state. In the case of CsCl, an unprecedented 2:2 complex is observed in the solid state that is characterized by two different ion-pair binding modes. One of these consists of a contact ion pair with the cesium cation and chloride anion both being bound within the central binding pocket and in direct contact with one another. The other mode involves a chloride anion bound to the pyrrole NH protons of a calixpyrrole subunit and a cesium cation sandwiched between two cone shaped calix[4]pyrroles originating from separate receptor units. In contrast to what is seen for CsF and CsCl, single-crystal X-ray structural analyses and (1)H NMR spectroscopic studies reveal that receptor 2 forms a 1:1 complex with CsNO(3), with the ions bound in the form of a contact ion pair. Thus, depending on the counteranion, receptor 2 is able to stabilize three different ion-pair binding modes with Cs(+), namely solvent-bridged, contact, and host-separated. PMID- 20359215 TI - Palladium-catalyzed asymmetric addition of diarylphosphines to enones toward the synthesis of chiral phosphines. AB - An asymmetric addition of diarylphosphines to beta-substituted enones under mild conditions using a chiral pincer-palladium catalyst has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 99% ee). PMID- 20359217 TI - Imaging structure sensitive catalysis on different shape-controlled platinum nanoparticles. AB - The structure sensitive catalytic activity for oxygen reduction reaction (ORR) on shape-controlled Pt nanoparticles (NPs) is directly imaged using scanning electrochemical microscopy (SECM). We synthesize and compare four types of Pt NPs: spherical, cubic, hexagonal, and tetrahedral-octahedral. Our SECM images show the hexagonal Pt NPs displaying the highest activity for ORR in two acid electrolytes. Meanwhile, cubic and tetrahedral-octahedral NPs drastically change their activity depending on specific adsorption of the different anions in solution. The NPs morphology produces predominant crystallographic planes at the surface of these shape-controlled Pt NPs, which are responsible for their different catalytic activity. Our results translate the studies on Pt single crystal electrodes present in the literature into Pt NPs that are useful as a catalyst in real fuel cells. PMID- 20359218 TI - NMR-based structural modeling of graphite oxide using multidimensional 13C solid state NMR and ab initio chemical shift calculations. AB - Chemically modified graphenes and other graphite-based materials have attracted growing interest for their unique potential as lightweight electronic and structural nanomaterials. It is an important challenge to construct structural models of noncrystalline graphite-based materials on the basis of NMR or other spectroscopic data. To address this challenge, a solid-state NMR (SSNMR)-based structural modeling approach is presented on graphite oxide (GO), which is a prominent precursor and interesting benchmark system of modified graphene. An experimental 2D (13)C double-quantum/single-quantum correlation SSNMR spectrum of (13)C-labeled GO was compared with spectra simulated for different structural models using ab initio geometry optimization and chemical shift calculations. The results show that the spectral features of the GO sample are best reproduced by a geometry-optimized structural model that is based on the Lerf-Klinowski model (Lerf, A. et al. Phys. Chem. B 1998, 102, 4477); this model is composed of interconnected sp(2), 1,2-epoxide, and COH carbons. This study also convincingly excludes the possibility of other previously proposed models, including the highly oxidized structures involving 1,3-epoxide carbons (Szabo, I. et al. Chem. Mater. 2006, 18, 2740). (13)C chemical shift anisotropy (CSA) patterns measured by a 2D (13)C CSA/isotropic shift correlation SSNMR were well reproduced by the chemical shift tensor obtained by the ab initio calculation for the former model. The approach presented here is likely to be applicable to other chemically modified graphenes and graphite-based systems. PMID- 20359219 TI - Oxidation catalysis of Nb(salan) complexes: asymmetric epoxidation of allylic alcohols using aqueous hydrogen peroxide as an oxidant. AB - Several optically active Nb(salan) complexes were synthesized, and their oxidation catalysis was examined. A dimeric mu-oxo Nb(salan) complex that was prepared from Nb(OiPr)(5) and a salan ligand was found to catalyze the asymmetric epoxidation of allylic alcohols using a urea-hydrogen peroxide adduct as an oxidant with good enantioselectivity. However, subsequent studies of the time course of this epoxidation and of the relationship between the ee of the ligand and the ee of the product indicated that the mu-oxo dimer dissociates into a monomeric species prior to epoxidation. Moreover, monomeric Nb(salan) complexes prepared in situ from Nb(OiPr)(5) and salan ligands followed by water treatment were found to catalyze the epoxidation of allylic alcohols better using aqueous hydrogen peroxide in CHCl(3)/brine or toluene/brine solution with high enantioselectivity ranging from 83 to 95% ee, except for the reaction of cinnamyl alcohol that showed a moderate ee of 74%. This is the first example of the highly enantioselective epoxidation of allylic alcohols using aqueous hydrogen peroxide as an oxidant. PMID- 20359220 TI - Palladium-catalyzed ortho-arylation of O-phenylcarbamates with simple arenes and sodium persulfate. AB - By palladium catalysis, the C-H bond functionalization of O-phenylcarbamates with simple arenes has been achieved using sodium persulfate (Na(2)S(2)O(8)), an inexpensive, easy-to-handle, and environmentally friendly oxidant. This oxidative cross-coupling involves two aromatic C-H bonds undergoing concomitant oxidation to furnish a new biaryl C-C linkage. Excellent reaction efficiencies and regioselectivities were observed with a range of electron-rich, electron-neutral, and electron-deficient arenes; minimal homocoupling of either component was observed. When two reactive C-H bonds are present on the O-phenylcarbamate, selective diarylation can be achieved via quadruple C-H bond functionalization. This work represents a rare example of using O-carbamates as directing groups for catalytic C-H bond activation. Additionally, a palladacycle obtained from an O phenylcarbamate was prepared and fully characterized. This trifluoroacetate bridged bimetallic Pd complex exhibits clean conversion to the ortho-arylation product upon treatment with simple arenes. The addition of trifluoroacetic acid (TFA) was found to be critical for successful cyclopalladation of O phenylcarbamates. We propose this oxidative arene cross-coupling occurs via two discrete C-H bond activations, namely cyclopalladation and electrophilic metalation, within a Pd(0/II) catalytic cycle. PMID- 20359221 TI - Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement. AB - NMR paramagnetic relaxation enhancement experiments were applied to the intrinsically disordered protein alpha-synuclein, the primary protein in Parkinson's disease, to directly characterize transient intermolecular complexes at neutral and low pH. At neutral pH, we observed weak N- to C-terminal interchain contacts driven by electrostatic interactions, while at low pH, the C- to C-terminal interchain interactions are significantly stronger and driven by hydrophobic contacts. Characterization of these first interchain interactions will provide fundamental insight into the mechanism of amyloid formation. PMID- 20359222 TI - 1H NMR, mechanism, and mononuclear oxidative activity of the antibiotic metallopeptide bacitracin: the role of D-Glu-4, interaction with pyrophosphate moiety, DNA binding and cleavage, and bioactivity. AB - The peptidyl antibiotic bacitracin (Bc) is one of the most widely used antibiotics which can bind divalent transition metal ions, including Mn(II), Co(II), Ni(II), Cu(II), and Zn(II). The metal binding is essential for its antimicrobial activity. Previous analysis of the hyperfine-shifted (1)H NMR signals of Co(II)-Bc A(1) revealed the structure of the metal binding environment and a potential hydrophobic site important for the bioactivity of this antibiotic. Co(II)-Bc in DMSO shows relatively sharper hyperfine-shifted (1)H NMR signals compared with the spectrum acquired in an aqueous solution, allowing more thorough analysis of the signals with 1D and 2D NMR methods. Pyrophosphate and derivatives bind to Co(II)-Bc to form kinetically inert ternary complexes. The coordinated D-Glu-4 is found detached from the metal center of metallobacitracin upon trimetaphosphate binding, implying its role in the antibiotic activity of Bc. We further demonstrate in this report the structure-function relationship on desamido-Bc of low antibiotic activity by the use of NMR, wherein D-Glu-4 is suggested to be important for the bioactivity of Bc. The interaction of the phospho-moiety with Bc is also reflected by DNA binding, wherein metal-free Bc does not bind DNA, whereas various metal complexes of Bc do. Cu(II)-Bc was further demonstrated to bind and oxidatively cleave DNA under reduction conditions in the air. It also exhibited a significant oxidative activity toward catechol oxidation, showing enzyme-like saturation kinetics with k(cat) = 7.0 x 10(-3) s(-1) and k(cat)/K(m) = 2.1 M(-1) s(-1) aerobically and k(cat) = 0.38 s( 1) and k(cat)/K(m) = 14.7 M(-1) s(-1) in the presence of 32 mM of H(2)O(2). The binding of pyrophosphate moiety to metallobacitracin, the detachment of d-Glu-4, and the significant oxidative activity of Cu(II)-Bc provide further insights into the bioactivity of this metallopeptide and Cu-oxygen chemistry. PMID- 20359223 TI - Determination of reduced cysteine in oenological cell wall fractions of Saccharomyces cerevisiae. AB - Compounds containing cysteine residues, such as glutathione, can affect the redox potential of must and wine by reduction of o-quinones and hydrogen peroxide. The oenological yeast cell wall fractions contain cysteine residues in their protein structure, and they could affect both oxidative and odor properties of wine. An analytical approach based on the derivatization of cysteinyl residues with p benzoquinone followed by reversed-phase high-performance liquid chromatography separation was developed to quantify glutathione and free and protein cysteine in 16 Saccharomyces cerevisiae strains and 12 commercial samples of yeast mannoproteins, hulls, and lysates. The chemical modifications induced by the Maillard reaction following the industrial preparation of such fractions were evaluated as well. Lysates showed the highest protein cysteine content and high contents of glutathione and free cysteine. Mannoproteins showed an intense Maillard reaction (furosine >60 mg/100 g protein), and most of the samples were able to bind thiol compounds with a potentially detrimental effect toward the thiol-related odors in wine. PMID- 20359225 TI - Targeting multiple chorismate-utilizing enzymes with a single inhibitor: validation of a three-stage design. AB - Chorismate-utilizing enzymes are attractive antimicrobial drug targets due to their absence in humans and their central role in bacterial survival and virulence. The structural and mechanistic homology of a group of these inspired the goal of discovering inhibitors that target multiple enzymes. Previously, we discovered seven inhibitors of 4-amino-4-deoxychorismate synthase (ADCS) in an on bead, fluorescent-based screen of a 2304-member one-bead-one-compound combinatorial library. The inhibitors comprise PAYLOAD and COMBI stages, which interact with active site and surface residues, respectively, and are linked by a SPACER stage. These seven compounds, and six derivatives thereof, also inhibit two other enzymes in this family, isochorismate synthase (IS) and anthranilate synthase (AS). The best binding compound inhibits ADCS, IS, and AS with K(i) values of 720, 56, and 80 microM, respectively. Inhibitors with varying SPACER lengths show the original choice of lysine to be optimal. Lastly, inhibition data confirm the PAYLOAD stage directs the inhibitors to the ADCS active site. PMID- 20359226 TI - Amino acid composition and antioxidant properties of pea seed ( Pisum sativum L.) enzymatic protein hydrolysate fractions. AB - The amino acid composition and antioxidant activities of peptide fractions obtained from HPLC separation of a pea protein hydrolysate (PPH) were studied. Thermolysin hydrolysis of pea protein isolate and ultrafiltration (3 kDa molecular weight cutoff membrane) yielded a PPH that was separated into five fractions (F1-F5) on a C(18) reverse phase HPLC column. The fractions that eluted later from the column (F3-F5) contained higher contents hydrophobic and aromatic amino acids when compared to fractions that eluted early or the original PPH. Fractions F3-F5 also exhibited the strongest radical scavenging and metal chelating activities; however, hydrophobic character did not seem to contribute to reducing power of the peptides. In comparison to glutathione, the peptide fractions had significantly higher (p < 0.05) ability to inhibit linoleic acid oxidation and chelate metals. In contrast, glutathione had significantly higher (p < 0.05) free radical scavenging properties than the peptide fractions. PMID- 20359227 TI - "Chain-like" trimetallic ruthenium complexes with C7 carbon-rich bridges: experimental and theoretical investigations of electronic communication tuning in five distinct oxidation states. AB - In this work, we report the synthesis and the electronic properties of the unique highly conjugated molecular wires trans-[Cl-(dppe)(2)Ru=C=C=(Ph)C-CH=(CH(3))C C[triple bond]C-(X)(2)Ru-C=C-C(CH(3))=CH-C(Ph)=C=C=Ru(dppe)(2)Cl](n+) (n = 2, X = dppe ([3a](OTf)(2)) and dppm ([3b](OTf)(2)) with three similar metal centers spanned by two odd-numbered unsaturated C(7) chains providing a 28 A long conjugated path and displaying five well-separated redox states (n = 0-4). Successive one-electron transfer steps were studied by means of cyclic voltammetry, EPR and UV-vis-NIR-IR spectroelectrochemistry. The electronic and physical properties of the different states were further rationalized with the help of DFT-based calculations. Upon one-electron reduction (n = 1), the single electron is delocalized over the two carbon chains through the central metal atom to an extent driven by the rotations within and between the chains. The second reduction (n = 0) involves the whole carbon-rich conjugated path of the molecule in a spin polarized scheme: one electron is delocalized over each chain, and the two electrons are antiferromagnetically coupled with a coupling on the order of kT. Interestingly, oxidation processes strongly involve both the metal atoms and the bridging ligands. The combined investigations reveal that the mono-oxidized system (n = 3) presents a spin density uniformly distributed between the metal atoms and the carbon atoms of the chains, whereas in the second oxidation state (n = 4) the compounds show a strong antiferromagnetic coupling on the order of 4 kT between the two single electrons localized in two distinct delocalized spin orbitals implying all the carbon atoms of the bridges and the three metal atoms. Thus, for the first time, electronic communication was fully evidenced and tuned in homonuclear trimetallic oligomeric carbon-rich systems in either an oxidation or a reduction process. PMID- 20359224 TI - Macrocyclic pyridyl polyoxazoles: selective RNA and DNA G-quadruplex ligands as antitumor agents. AB - The synthesis of a series of 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new macrocycles were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) and BCRP (KBH5.0). Macrocycles in which the pyridyl polyoxazole moiety is linked by a 1,3-bis(aminomethyl)phenyl group with a 5-(2 aminoethyl)- (18) or a 5-(2-dimethylaminoethyl)- substituent (19) displayed the greatest cytotoxic potency. These compounds exhibit exquisite selectivity for stabilizing G-quadruplex DNA with no stabilization of duplex DNA or RNA. Compound 19 stabilizes quadruplex mRNA that encodes the cell-cycle checkpoint protein kinase Aurora A to a greater extent than the quadruplex DNA of a human telomeric sequence. These data may suggest a role for G-quadruplex ligands interacting with mRNA being associated with the biological activity of macrocyclic polyoxazoles. Compound 19 has significant in vivo anticancer activity against a human breast cancer xenograft (MDA-MB-435) in athymic nude mice. PMID- 20359228 TI - Lignans from the tuber-barks of Colocasia antiquorum var. esculenta and their antimelanogenic Activity. AB - Colocasia antiquorum var. esculenta , a variant of C. antiquorum , commonly known as "Imperial Taro", is an edible vegetable in many tropical and subtropical regions of the world. This study with the aim of evaluating the potential of C. antiquorum var. esculenta as a functional food with a depigmenting effect resulted in the identification of a new sesquilignan, named colocasinol A (1), and a new acyclic phenylpropane lignanamide, named cis-grossamide K (2), together with 10 known compounds (3-12). The identification and structural elucidation of these compounds were based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data analysis as well as high-resolution fast atom bombardment mass spectrometry (FABMS) and electron impact mass spectrometry (EIMS). Quantitation of the melanin contents and cell viability in murine melanocyte melan-a cells was used to assess the antimelanogenic activities of the isolated compounds. Among them, cis-grossamide K (2), isoamericanol A (3), americanol A (4), 2-hydroxy-3,2' dimethoxy-4'-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl (5), and (-)-pinoresinol (6) showed inhibitory effects on melanin production. Compounds 2, 5, and 6 exerted a particularly strong antimelanogenic activity on the cells without high cell toxicity (IC(50) = 54.24, 53.49, and 56.26 microM, and LD(50) = 163.60, 110.23, and >500 microM, respectively). PMID- 20359229 TI - Synthesis of notoamide J: a potentially pivotal intermediate in the biosynthesis of several prenylated indole alkaloids. AB - An efficient total synthesis of notoamide J, a new prenylated indole alkaloid and potential biosynthetic precursor, is described herein. Starting from L-proline and a substituted tryptophan derivative, this synthesis also employs an oxidation and pinacol rearrangement for the formation of the oxindole in the final step. PMID- 20359230 TI - Study on the relevance between beany flavor and main bioactive components in Radix Astragali. AB - Beany flavor is a traditional sensory indicator for evaluating the quality of Radix Astragali (RA or "Huangqi" in Chinese). A RA root with a strong beany flavor is considered to be good quality in Chinese medicine. However, there is neither a study reporting volatile compounds contributing to RA beany flavor nor the relevance between beany flavor and the quality of RA. In this study, we assessed the quantification of beany flavor substance and main bioactive metabolites. The results showed that hexanal was a major volatile component contributing to the beany flavor in RA. The value of hexanal was significantly related to the origin and growth age of RA, indicating that the component could be used as a volatile indicator for the distinction of RA. Statistical analysis further demonstrated that hexanal, astragaloside IV, and total polysaccharides were primary indicators and total isoflavonoids, astragalosides, calycosin, and formononetin were the secondary indicators for quality control of RA. Correlation analysis showed that the level of hexanal was positively associated with the concentration of astragaloside IV and total polysaccharides. Our study demonstrated that aroma is one of the most important quality attributes of RA and will help to understand the role of aroma in quality assessment of traditional Chinese medicines. PMID- 20359231 TI - Collapse of highly charged polyelectrolytes triggered by attractive dipole-dipole and correlation-induced electrostatic interactions. AB - In the first part of the paper, we study the collapse of flexible highly charged polyelectrolyte chains induced by attractive dipole-dipole interactions. The latter emerge due to the formation of dipoles between the chain monomers and counterions condensed on the polyelectrolyte from solution. Using the statistics of slightly perturbed Gaussian polymers, we obtain the scaling relations for the chain dimensions as a function of polyelectrolyte linear charge density in the limit of compacting chains. The results are in good agreement with the outcomes of recent molecular dynamics simulations of the collapse of flexible polyelectrolytes in the presence of explicit counterions. In the second part, we analyze the results of molecular dynamics simulations for the complex formation by two highly charged polyelectrolyte chains carrying opposite charges. We use the scaling arguments based on the picture of complexation of electrostatic blobs in order to rationalize the size of the complexes of two polyelectrolyte chains in the collapsed state. Similar scaling relation for the complex size was recently obtained in computer simulations of complexation of diblock polyampholytes and was described theoretically on the basis of similar electrostatic blob concepts. We also analyze the density of complexes formed and polyelectrolyte linear charge densities required for the onset onto the collapse as a function of interaction strength between the monomers. In both parts of the paper, we overview the scaling relationships obtained for similar systems with alternating charges from other theoretical approaches. PMID- 20359232 TI - Engineering metal organic frameworks for heterogeneous catalysis. PMID- 20359234 TI - Enhanced thermoelectric performance of single-walled carbon nanotubes/polyaniline hybrid nanocomposites. AB - Hybrid nanocomposites containing carbon nanotubes (CNTs) and ordered polyaniline (PANI) have been prepared through an in situ polymerization reaction using a single-walled nanotube (SWNT) as template and aniline as reactant. TEM, SEM, XRD, and Raman analyses show that the polyaniline grew along the surface of CNTs forming an ordered chain structure during the SWNT-directed polymerization process. The SWNT/PANI nanocomposites show both higher electrical conductivity and Seebeck coefficient as compared to pure PANI, which could be attributed to the enhanced carrier mobility in the ordered chain structures of the PANI. The maximum electrical conductivity and Seebeck coefficient of composites reach 1.25 x 10(4) S m(-1) and 40 microV K(-1), respectively, and the maximum power factor is up to 2 x 10(-5) W m(-1) K(-2), more than 2 orders of magnitude higher than the pure polyaniline. This study suggests that constructing highly ordered chain structure is a novel and effective way for improving the thermoelectric properties of conducting polymers. PMID- 20359233 TI - Cerium(IV) ammonium nitrate as a catalyst in organic synthesis. PMID- 20359235 TI - p-Type PbSe and PbS quantum dot solids prepared with short-chain acids and diacids. AB - We show that ligand exchange with short-chain carboxylic acids (formic, acetic, and oxalic acid) can quantitatively remove oleic acid from the surface of PbSe and PbS quantum dot (QD) films to yield p-type, carboxylate-capped QD solids with field-effect hole mobilities in the range of 10(-4)-10(-1) cm(2) V(-1) s(-1). For a given chemical treatment, PbSe devices have 10-fold higher mobilities than PbS devices because of stronger electronic coupling among the PbSe QDs and possibly a lower density of surface traps. Long-term optical and electrical measurements (i) show that carboxylate-capped PbSe QD films oxidize much more gradually in air than do thiol-capped PbSe films and (ii) quantify the slower and less extensive oxidation of PbS relative to PbSe QDs. We find that whereas the hole mobility of thiol-capped samples decreases continuously with time in air, the mobility of carboxylate-capped films first increases by an order of magnitude over several days before slowly decreasing over weeks. This behavior is a consequence of the more robust binding of carboxylate ligands to the QD surface, such that adsorbed oxygen and water initially boost the hole mobility by passivating surface states and only slowly degrade the ligand passivation to establish an oxide shell around each QD in the film. The superior hole mobilities and oxidation resistance of formic- and acetic-treated QD solids may prove useful in constructing efficient, stable QD photovoltaic devices. PMID- 20359236 TI - Two-dimensional diffusion-ordered NMR spectroscopy as a tool for monitoring functionalized carbon nanotube purification and composition. AB - Functionalized carbon nanotube (CNT) derivatives are currently under thorough investigation in different biomedical investigations. In this field of research, the composition of sample either in terms of covalently attached or physisorbed moieties can greatly affect the observed results and hamper the comparison between different studies. Therefore, the availability of a fast and reliable analytical technique to assess both the type of interaction (covalent vs noncovalent) and the composition of CNT conjugates is of great importance. Here we describe that the two-dimensional diffusion-ordered (DOSY) NMR spectroscopy is extremely useful to discriminate between conjugated and unconjugated polyethylene glycol groups in samples obtained by condensation with oxidized single-walled carbon nanotubes (SWNTs). This fast and nondestructive technique allows us to follow the removal of unconjugated polyethylene glycol chains during the purification. In particular, DOSY analysis reveal that about 1/3 (wt %) of the polyethylene glycol used for the condensation remained physisorbed to functionalized SWNTs after dialysis. Complete elimination of physisorbed polyethylene glycol was achieved using diafiltration. PMID- 20359237 TI - HPPD: ligand- and target-based virtual screening on a herbicide target. AB - Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment. PMID- 20359238 TI - Fluorogenic peptide substrates for serine and threonine phosphatases. AB - A new fluorescent assay for Ser/Thr protein phosphatases has been developed. Hydrolysis of a phosphoSer residue liberates the Ser hydroxyl group, which induces a cyclization reaction on the N-terminal carbamate and releases a fluorescent reporter. Sequence selectivity is observed using several peptide substrates against alkaline phosphatase (ALP), bacteriophage lambda protein phosphatase (lambda-PPase), and vaccinia H1 related phosphatase (VHR). These studies suggest that the assay could be a useful tool for profiling the substrate specificities of medicinally important phosphatases. PMID- 20359239 TI - Decorating parylene-coated glass with ZnO nanoparticles for antibacterial applications: a comparative study of sonochemical, microwave, and microwave plasma coating routes. AB - A glass substrate, coated with a Parylene film, was coated with ZnO by three different methods: ultrasound, microwave, and microwave-plasma irradiation. These coating modes are simple, efficient, and environmentally friendly one-step processes. The structure of the coated products was characterized and compared using methods such as XRD, HR-SEM, EDS, RBS, and optical spectroscopy. Coating by ZnO nanoparticles was achieved for all three approaches. The products were found to differ in their particle sizes, coating thickness, and depth of penetration. All of the ZnO-Parylene-glass composites demonstrated a significant antibacterial activity against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) strains. PMID- 20359240 TI - Symmetric six-fold arrays of photo- and electrochromic dithienylethene switches. AB - The direct synthesis of six-fold symmetric hexaphenylbenzenes with multiple photochromic dithienylethene units via a cobalt-catalyzed cyclotrimerization is reported. This approach allows for six photochromic units to be held in proximity with a well-defined spatial separation without affecting the photochromic properties of each unit. PMID- 20359241 TI - Baiting proteins with C60. AB - About 20 proteins are known to modify their activity upon interaction with C60. Their structures are present in a database that includes more than 1200 protein structures selected as possible targets for drugs and to represent the entire Protein Data Bank. The set was examined with an algorithm that appraises quantitatively the interaction of C60 and the surface of each protein. The redundancy of the set allows to establish the predictive power of the approach that finds explicitly the most probable site where C60 docks on each protein. About 80% of the known fullerene binding proteins fall in the top 10% of scorers. The close match between the model and experiments vouches for the accuracy of the model and validates its predictions. The sites of docking are shown and discussed in view of the existing experimental data available for protein-C60 interaction. A closer exam of the 10 top scorers is discussed in detail. New proteins that can interact with C60 are identified and discussed for possible future applications as drug targets and fullerene derivatives bioconjugate materials. PMID- 20359242 TI - Investigating active site of gold nanoparticle Au55(PPh3)12Cl6 in selective oxidation. AB - We present an ab initio investigation of structural, electronic, catalytic, and selective properties of the ligand-covered gold nanoparticle Au55(PPh3)12Cl6 and associated model clusters. The catalytic activity of the Au55(PPh3)12Cl6 nanoparticle in the presence of O2 stems from a combined effect of triphenylphosphine ligands and surface structure of the "magic-number" quasi icosahedral Au55 core, which entails numerous ligand-encompassed triangle Au6 faces as the active sites. Under the Eley-Rideal mechanism, the "triangle-socket" active site not only can accommodate one pre-adsorbed O2 (which is subsequently activated to the superoxo species) with one styrene molecule at a time but also can provide spatial confinement which favors the formation of an oxametallacycle intermediate that leads to unique selectivity in styrene oxidation. PMID- 20359243 TI - Nanoporous carbon supercapacitors in an ionic liquid: a computer simulation study. AB - Supercapacitors composed of carbon nanotube (CNT) micropores in the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI+BF4(-)) are studied via molecular dynamics (MD)computer simulations. It is found that the distribution of RTIL ions inside the micropore varies significantly with the pore size. Internal solvation of small (6,6) and (7,7) CNTs with an electrified interior wall is effected almost exclusively via counterions. Surprisingly, these counterions, even though they all have the same charge, lead to a charge density characterized by multiple layers with alternating signs. This intriguing feature is attributed to the extended nature of RTIL ion charge distributions, which result in charge separation through preferential orientation inside the electrified nanotubes. In the case of larger (10,10) and (15,15) CNTs, counterions and coions develop multilayer solvation structures. The specific capacitance normalized to the pore surface area is found to increase as the CNT diameter decreases from (15,15) to (7,7). As the pore size further reduces from (6,6) to(5,5), however, the specific capacitance diminishes rapidly. These findings are in excellent agreement with recent experiments with carbon-based materials. A theoretical model based on multiple charge layers is proposed to understand both the MD and experimental results. PMID- 20359244 TI - A new family of sandwich-type polytungstophosphates containing two types of metals in the central belt: M'2M2(PW9O34)(2)(12-) (M' = Na or Li, M = Mn2+, Co2+, Ni2+, and Zn2+). AB - A new family of sandwich-type polytungstophosphates containing two different types of metals in the central belt, M'(2)M(2)(PW(9)O(34))(2)(12-) (M' = Na or Li, M = Mn(2+), Co(2+), Ni(2+), and Zn(2+)), have been synthesized and characterized by infrared spectroscopy, (31)P solution NMR spectroscopy, and elemental analysis. Compounds Na(2)Co(2)(PW(9)O(34))(2)(12-) (Na2Co2), Na(2)Ni(2)(PW(9)O(34))(2)(12-) (Na2Ni2), Li(2)Ni(2)(PW(9)O(34))(2)(12-) (Li2Ni2), Na(2)Mn(2)(PW(9)O(34))(2)(12-) (Na2Mn2), and Li(2)Zn(2)(PW(9)O(34))(2)(12-) (Li2Zn2) were characterized by X-ray crystallography. All these compounds have similar structures, in which two transition-metal ions and two alkali metal ions (sodium or lithium) are sandwiched between two [B-alpha-PW(9)O(34)](9-) units; the transition and alkali metals reside in the internal and external (solvent exposed) positions of the central belt, respectively. By adding LiCl to aqueous solutions of compounds Na2M2, lithium-sodium exchanges in the external belt positions are observed by (31)P solution NMR spectroscopy and X-ray crystallography. Magnetic measurements indicate ferromagnetic exchange interactions between the two Ni(2+) ions in Na2Ni2 at 10-300 K and the two Co(2+) ions in Na2Co2 at 6-30 K. In contrast, Na2Mn2 exhibits an antiferromagnetic interaction between the Mn(2+) ions at 2-50 K. PMID- 20359245 TI - Structure and function of intact photosystem 1 monomers from the cyanobacterium Thermosynechococcus elongatus. AB - Until now, the functional and structural characterization of monomeric photosystem 1 (PS1) complexes from Thermosynechococcus elongatus has been hampered by the lack of a fully intact PS1 preparation; for this reason, the three-dimensional crystal structure at 2.5 A resolution was determined with the trimeric PS1 complex [Jordan, P., et al. (2001) Nature 411 (6840), 909-917]. Here we show the possibility of isolating from this cyanobacterium the intact monomeric PS1 complex which preserves all subunits and the photochemical activity of the isolated trimeric complex. Moreover, the equilibrium between these complexes in the thylakoid membrane can be shifted by a high-salt treatment in favor of monomeric PS1 which can be quantitatively extracted below the phase transition temperature. Both monomers and trimers exhibit identical posttranslational modifications of their subunits and the same reaction centers but differ in the long-wavelength antenna chlorophylls. Their chlorophyll/P700 ratio (108 for the monomer and 112 for the trimer) is slightly higher than in the crystal structure, confirming mild preparation conditions. Interaction of antenna chlorophylls of the monomers within the trimer leads to a larger amount of long wavelength chlorophylls, resulting in a higher photochemical activity of the trimers under red or far-red illumination. The dynamic equilibrium between monomers and trimers in the thylakoid membrane may indicate a transient monomer population in the course of biogenesis and could also be the basis for short-term adaptation of the cell to changing environmental conditions. PMID- 20359246 TI - In vitro recombination and inverted terminal repeat binding activities of the Mcmar1 transposase. AB - The Mcmar1 mariner element (MLE) presents some intriguing features with two large, perfectly conserved, 355 bp inverted terminal repeats (ITRs) containing two 28 bp direct repeats (DRs). The presence of a complete ORF in Mcmar1 makes it possible to explore the transposition of this unusual MLE. Mcmar1 transposase (MCMAR1) was purified, and in vitro transposition assays showed that it is able to promote ITR-dependent DNA cleavages and recombination events, which correspond to plasmid fusions and transpositions with imprecise ends. Further analyses indicated that MCMAR1 is able to interact with the 355 bp ITR through two DRs: the EDR (external DR) is a high-affinity binding site for MCMAR1, whereas the IDR (internal DR) is a low-affinity binding site. The main complex detected within the EDR contained a transposase dimer and only one DNA molecule. We hypothesize that the inability of MCMAR1 to promote precise in vitro transposition events could be due to mutations in its ORF sequence or to the specific features of transposase binding to the ITR. Indeed, the ITR region spanning from EDR to IDR resembles a MITE and could be bent by specific host factors. This suggests that the assembly of the transposition complex is more complex than that of those involved in the mobility of the Mos1 and Himar1 mariner elements. PMID- 20359247 TI - Effects of the nature and concentration of salt on the interaction of the HIV-1 nucleocapsid protein with SL3 RNA. AB - The mature nucleocapsid protein of HIV-1, NCp7, and the NC domains in gag precursors are attractive targets for anti-AIDS drug discovery. The stability of the 1:1 complex of NCp7 with a 20mer mimic of stem-loop 3 RNA (SL3, also called psi-RNA, in the packaging domain of genomic RNA) is strongly affected by changes in ionic strength. NC domains recognize and specifically package genomic HIV-1 RNA, while electrostatic attractions and high concentrations of protein and RNA drive NCp7 to completely coat the RNA in the mature virion. The specific interactions of NCp7 binding to loop bases of SL3 produce 1:1 complexes in solutions that have a NaCl concentration of >or=0.2 M, while the electrostatic interactions can dominate at 65 years, and represent 25% of those undergoing surgery. The proportion of the population aged >or=65 years is rapidly growing, and an increasing number are affected with cardiovascular disease. The older person is a high-risk patient. This is because of their altered physiology and associated co-morbidities, as well as the pharmacokinetic and pharmacodynamic changes that may alter drug responses. There is considerable variability seen in the physical and physiological states of individual patients within the older population. This has an important impact on choosing a safe anaesthetic technique for each individual, which in turn can influence the morbidity and mortality in this population. The physiological changes in the aging cardiovascular system affect the arterial and venous vasculature, myocardium and autonomic nervous system, making the older person more prone to cardiovascular instability. In addition to the physiological changes, the cardiovascular status of the older person tends to be compromised by associated pathological conditions that are more common with increasing age. Pharmacokinetic and pharmacodynamic changes must be taken into account when deciding about drug dosing in this age group. Aspects of dose reduction, titration of drugs, dosing intervals and the pharmacodynamic effects of each class of drug are explained in detail in the text. The major challenge in anaesthesia for the older person with cardiovascular disease is maintenance of haemodynamic stability, particularly in the face of reduced physiological reserve and capability to respond to periods of instability. An appropriate anaesthetic technique must be selected to minimize haemodynamic changes and maintain near normal physiological status. The other key objective is to minimize the incidence of adverse outcomes, such as perioperative myocardial ischaemia/infarction, arrhythmias, heart failure, postoperative cognitive dysfunction and stroke. No single anaesthetic regimen or agent can be advocated. Knowledge of the pharmacokinetic and pharmacodynamic principles of anaesthetic agents and their altered response in elderly patients is essential when selecting an anaesthetic agent. This article provides a practical guide to the selection and use of general anaesthetic agents in older patients with cardiovascular disorders, highlighting the differences among various agents. PMID- 20359260 TI - Multiple sclerosis in the elderly patient. AB - Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease of the CNS that is typically diagnosed in the second or third decade of life. It is generally believed that over the last few decades the life expectancy of patients with adult onset MS (AOMS) has approached that of the general population as a result of better medical and nursing care. Thus, an increasing number of MS patients are entering or have reached senescence. A second group of elderly patients with MS that may be very different in terms of disease pathogenesis are patients with late onset MS (LOMS). The diagnosis in LOMS patients can be challenging because of a large number of age-associated MS differential diagnoses, atypical presentations, a low index of suspicion and the lack of diagnostic criteria specific to this age group. Also, specific problems these patients encounter have only recently become a focus of attention. Changes in renal and hepatic function with age, in addition to the coexistence of medical co morbidities, require special attention in the management of elderly patients with MS. In this review we outline the characteristics of senescent AOMS and LOMS patients. In addition, we discuss therapeutic strategies in elderly patients with MS based on our knowledge of immunosenescence and age-associated characteristics of this disorder. Given the overall aging of the population, focusing on these two patient groups appears highly relevant. PMID- 20359261 TI - Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson's disease. AB - Dopamine receptor agonists provide a viable alternative or adjunct to levodopa therapy in Parkinson's disease and are associated with fewer motor complications and dyskinesia. However, all available dopamine agonists may cause profound adverse effects in some patients. In many cases, these adverse effects amplify non-motor symptoms that people with Parkinson's disease may already be experiencing. Nausea from dopamine agonists generally lessens with time and may be responsive to both antiemetic therapy and complementary remedies, such as ginger, peppermint and chamomile. Unfortunately, compulsive behaviours, as well as peripheral oedema caused by dopamine agonists, are poorly responsive to pharmacological therapy and require a reduction or discontinuation of agonist therapy. Somnolence and associated sleep attacks generally require elimination of the agonist or the use of a stimulating agent. The necessity of treatment for hallucinations and psychosis associated with dopamine agonists must be thoroughly evaluated prior to initiating therapy. If a medication is initiated for hallucinations or psychosis, quetiapine or clozapine are agents of choice. Orthostatic hypotension, though not always symptomatic, responds well to nonpharmacological strategies and medications, including indometacin, midodrine and fludrocortisone. Care must be taken to educate patients with Parkinson's disease about the common adverse effects of dopamine agonists and what can be done to lessen them. PMID- 20359263 TI - Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly finns: a population-based intervention study. AB - BACKGROUND: Pharmacoepidemiological studies assessing the associations between psychotropic drug use and adverse events in the elderly frequently employ automated pharmacy databases as the source of exposure data. However, information on the validity of these databases for estimating psychotropic drug exposures in elderly people is scarce. OBJECTIVE: This study evaluated the validity of the Finnish Prescription Register for estimating current exposures to psychotropic drugs in elderly people. Furthermore, the potential change in the validity over time was determined. METHODS: This was a population-based intervention study (GeMS; Geriatric Multidisciplinary Strategy for the Good Care of the Elderly) conducted between 2004 and 2007. Initially, 1000 randomly selected persons aged >or=75 years living in the City of Kuopio, Finland, in November 2003 were invited to participate in the study. Of these, 716 agreed to participate at baseline (2004) and 570 were still available for 3-year follow-up (2007). The validity of the Prescription Register was assessed by comparing it with the self-reported information collected by interviews in 2004 and in 2007 in the GeMS study. Using the self-reported data as a reference standard, sensitivity, specificity and Cohen's kappa statistic (measure of inter-rater agreement for qualitative [categorical] items) with 95% confidence intervals were computed for different categories and subcategories of psychotropic drugs, applying fixed-time windows of 4, 6 and 12 months. RESULTS: In 2007, the sensitivity varied between psychotropic categories and subcategories, being generally highest with the 12 month time window (0.57-0.96). The specificity was highest with the 4-month time window (0.94-0.99), showing a slight tendency to decrease with an extended time window. The sensitivity and specificity were highest for antidepressants and antipsychotics, followed by benzodiazepines. The agreement was almost perfect (kappa = 0.81-1.00) or substantial (kappa = 0.61-0.80) for all categories and subcategories of psychotropic drugs. Few differences in validity were observed between the two years. CONCLUSION: Using self-reported data as a reference standard, the Prescription Register provides valid information on current exposures to antidepressants and antipsychotics in elderly people if the time window is selected with adequate consideration. However, the validity is lower for benzodiazepines, suggesting that other sources of information should be considered when performing pharmacoepidemiological studies. PMID- 20359262 TI - Assessment and management of pressure ulcers in the elderly: current strategies. AB - Pressure ulcers (pressure sores) continue to be a common health problem, particularly among the physically limited or bedridden elderly. The problem exists within the entire health framework, including hospitals, clinics, long term care facilities and private homes. For many elderly patients, pressure ulcers may become chronic for no apparent reason and remain so for prolonged periods, even for the remainder of the patient's lifetime. A large number of grade 3 and 4 pressure ulcers become chronic wounds, and the afflicted patient may even die from an ulcer complication (sepsis or osteomyelitis). The presence of a pressure ulcer constitutes a geriatric syndrome consisting of multifactorial pathological conditions. The accumulated effects of impairment due to immobility, nutritional deficiency and chronic diseases involving multiple systems predispose the aging skin of the elderly person to increasing vulnerability. The assessment and management of a pressure ulcer requires a comprehensive and multidisciplinary approach in order to understand the patient with the ulcer. Factors to consider include the patient's underlying pathologies (such as obstructive lung disease or peripheral vascular disease), severity of his or her primary illness (such as an infection or hip fracture), co-morbidities (such as dementia or diabetes mellitus), functional state (activities of daily living), nutritional status (swallowing difficulties), and degree of social and emotional support; focusing on just the wound itself is not enough. An understanding of the physiological and pathological processes of aging skin throws light on the aetiology and pathogenesis of the development of pressure ulcers in the elderly. Each health discipline (nursing staff, aides, physician, dietitian, occupational and physical therapists, and social worker) has its own role to play in the assessment and management of the patient with a pressure ulcer. The goals of treating a pressure ulcer include avoiding any preventable contributing circumstances, such as immobilization after a hip fracture or acute infection. Once a pressure ulcer has developed, however, the goal is to heal it by optimizing regional blood flow (by use of a stent or vascular bypass surgery), managing underlying illnesses (such as diabetes, hypothyroidism or congestive heart failure) and providing adequate caloric and protein intake (whether through use of dietary supplements by mouth or by use of tube feeding). If the ulcer has become chronic, the ultimate goal changes from healing the wound to controlling symptoms (such as foul odour, pain, discomfort and infection) and preventing complications, thereby contributing to the patient's overall well-being; providing support for the patient's family is also important. Recent advances in wound dressings allow for greater control of symptoms and prevention of complications, and have also enabled the affected patient to be integrated more readily into the family setting and in the community at large. Ethical and end-of-life issues must also be addressed soon after the wound has become chronic. This article discusses the pathogenesis of pressure ulcer development in the elderly in relation to concomitant diseases, risk factor assessment and the management of such ulcers. PMID- 20359265 TI - Organic foods contain higher levels of certain nutrients, lower levels of pesticides, and may provide health benefits for the consumer. AB - The multi-billion dollar organic food industry is fueled by consumer perception that organic food is healthier (greater nutritional value and fewer toxic chemicals). Studies of the nutrient content in organic foods vary in results due to differences in the ground cover and maturity of the organic farming operation. Nutrient content also varies from farmer to farmer and year to year. However, reviews of multiple studies show that organic varieties do provide significantly greater levels of vitamin C, iron, magnesium, and phosphorus than non-organic varieties of the same foods. While being higher in these nutrients, they are also significantly lower in nitrates and pesticide residues. In addition, with the exception of wheat, oats, and wine, organic foods typically provide greater levels of a number of important antioxidant phytochemicals (anthocyanins, flavonoids, and carotenoids). Although in vitro studies of organic fruits and vegetables consistently demonstrate that organic foods have greater antioxidant activity, are more potent suppressors of the mutagenic action of toxic compounds, and inhibit the proliferation of certain cancer cell lines, in vivo studies of antioxidant activity in humans have failed to demonstrate additional benefit. Clear health benefits from consuming organic dairy products have been demonstrated in regard to allergic dermatitis. PMID- 20359266 TI - Biomarker-guided interventions of clinically relevant conditions associated with autism spectrum disorders and attention deficit hyperactivity disorder. AB - Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are common and complex neurodevelopmental conditions. Diagnostic criteria for these conditions have traditionally relied solely on behavioral criteria without consideration for potential biomedical underpinnings. Newer evidence, however, reveals that ASDs are associated with: oxidative stress; decreased methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal dysbiosis; increased toxic metal burden; immune dysregulation, characterized by a unique inflammatory bowel disease and immune activation of neuroglial cells; and ongoing brain hypoperfusion. Many of these same problems are common features in children with ADHD. These medical conditions, whether co-morbidities or etiopathogenic, would be expected to have synergistically negative effects on the development, cognition, focus, and attention of affected children. It is likely these biological abnormalities contribute significantly to the behavioral symptoms intrinsic in these diagnoses. However, treatment for these underlying medical disorders is clinically justified, even if no clear immediate behavioral improvements are observed. This article reviews the medical literature and discusses the authors clinical experience using various biomarkers for measuring oxidative stress, methylation capacity and transsulfuration, immune function, gastrointestinal problems, and toxic metal burden. These biomarkers provide useful guides for selection, efficacy, and sufficiency of biomedical interventions. The use of these biomarkers is of great importance in young children with ADHD or individuals of any age with ASD, because typically they cannot adequately communicate regarding their symptoms. PMID- 20359268 TI - A review of homeopathic research in the treatment of respiratory allergies. AB - There are conceptual and historical links between homeopathic medicine and modern allergy desensitization treatment. Conventional allergy desensitization and homeopathic treatment both utilize small doses of substances that might cause symptoms in order to prevent or treat a hypersensitive state. Homeopathy has historically been associated with allergy treatment. This article reviews evidence from controlled trials for the use of homeopathy in respiratory allergies. Several clinical trials, many of which were published in "high impact" conventional medical journals, describe significant effects of homeopathic treatment in allergic patients. Most of these clinical studies have been deemed to be high quality trials, according to the three most commonly referenced meta analyses of homeopathic research. Basic in vitro experimental studies also provide evidence that the effects of homeopathy differ from placebo. PMID- 20359267 TI - Immune-modifying and antimicrobial effects of Eucalyptus oil and simple inhalation devices. AB - Eucalyptus oil (EO) and its major component, 1,8-cineole, have antimicrobial effects against many bacteria, including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA), viruses, and fungi (including Candida). Surprisingly for an antimicrobial substance, there are also immune stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Of the white blood cells, monocytes and macrophages are most affected, especially with increased phagocytic activity. Application by either vapor inhalation or oral route provides benefit for both purulent and non-purulent respiratory problems, such as bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). There is a long history of folk usage with a good safety record. More recently, the biochemical details behind these effects have been clarified. Although other plant oils may be more microbiologically active, the safety of moderate doses of EO and its broad-spectrum antimicrobial action make it an attractive alternative to pharmaceuticals. EO has also been shown to offset the myelotoxicity of one chemotherapy agent. Whether this is a general attribute that does not decrease the benefit of chemotherapy remains to be determined. This article also provides instruction on how to assemble inexpensive devices for vapor inhalation. PMID- 20359269 TI - Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. AB - OBJECTIVE: To evaluate the effectiveness of vitamin E, evening primrose oil (EPO), and the combination of vitamin E and EPO for pain control in women with cyclical mastalgia. PROCEDURE: A double-blind, randomized, placebo-controlled trial was conducted at two U.S. academic medical centers. Eighty-five women with premenstrual cyclical breast discomfort were enrolled. Participants were randomly assigned to one of four six-month oral treatments: vitamin E (1,200 IU per day), EPO (3,000 mg per day), vitamin E (1,200 IU per day) plus EPO (3,000 mg per day), or double placebo. The primary outcome measure was change in breast pain, measured by the modified McGill Pain Questionnaire at enrollment and at six months. RESULTS: Forty-one patients completed the study. Intent-to-treat analysis (pretesting and post testing) showed a difference in worst-pain improvement with the treatments EPO (p=0.005), vitamin E (p=0.04), and EPO plus vitamin E (p=0.05), but no difference with placebo (p=0.93). Results from two-sample t-test showed a nonsignificant decrease in cyclical mastalgia individually for the three treatment groups compared with the placebo group (EPO, p=0.18; vitamin E, p=0.10; and EPO plus vitamin E, p=0.16). The data were also analyzed with the separation test by Aickin, which showed a trend toward a reduction of cyclical mastalgia with vitamin E and EPO individually and in combination. CONCLUSION: Daily doses of 1,200 IU vitamin E, 3,000 mg EPO, or vitamin E and EPO in combination at these same dosages taken for six months may decrease the severity of cyclical mastalgia. PMID- 20359270 TI - The effect of a novel viscous polysaccharide along with lifestyle changes on short-term weight loss and associated risk factors in overweight and obese adults: an observational retrospective clinical program analysis. AB - BACKGROUND: Viscous soluble dietary fiber has been demonstrated to reduce postprandial glycemia and may promote satiety. PolyGlycopleX (PGX) is a highly viscous polysaccharide manufactured by reacting glucomannan with other soluble polysaccharides using a proprietary process (EnviroSimplex). The resulting polysaccharide (alpha-D-glucurono-alpha-D-manno-beta-D-manno-beta-D-glucan, alpha L-gulurono-beta-D-mannuronan, beta-D-gluco-beta-D-mannan, alpha-D-glucurono-alpha D-manno-beta-D-manno-beta-D-gluco, alpha-L-gulurono-beta-D-mannurono, beta-D gluco-beta-D-mannan) is a novel entity with the highest viscosity and water holding capacity of currently known fibers. MATERIALS AND METHODS: A total of 29 sedentary overweight or obese adults (23 women; six men), ages 20-65 with a body mass index (BMI) range of 25 kg/m(2) to 36 kg/m(2) participated in a clinical weight-loss program. PGX (5 g) was consumed with 500 mL water, 5-10 minutes before each meal, 2-3 times daily for 14 weeks. RESULTS: Significant reductions were observed (p less than 0.05) in weight (-5.79 +/- 3.55 kg), waist circumference (-12.07 +/- 5.56 cm), and percentage body fat (-2.43 +/- 2.39 percent) compared to baseline values. In addition, subjects employing PGX had a significant reduction of 19.26 percent (n=17; p less than 0.05) and 25.51 percent (n=16; p less than 0.05) in total and LDL plasma cholesterol values, respectively, at the end of the study period. CONCLUSION: The consumption of PGX in concert with lifestyle modifications may be a useful strategy for weight loss in overweight and obese individuals. PMID- 20359271 TI - Acetyl-L-carnitine. Monograph. PMID- 20359272 TI - Krill oil. Monograph. PMID- 20359273 TI - The effect of a four-year caries prevention programme started at six-years of age on crowding in the early permanent dentition. AB - AIM: This research was conducted to study the effect of school-based caries prevention program on the crowding in the early permanent dentition. STUDY DESIGN: upper and lower arch crowding was compared between 78 subjects who had received a successful caries prevention programme and 94 control subjects. MATERIALS AND METHODS: A study model was taken for each of the subjects. From these models the arch perimeter and the total tooth width were determined and the degree of upper and lower arch crowding was calculated. RESULTS: The total mesiodistal tooth widths in the upper and the lower arches in the prevention group were not significantly different from the total mesiodistal tooth widths in the control group. Nevertheless, due to a smaller arch perimeter, the degree of crowding was significantly greater in the control group in both arches. STATISTICS: Independent t-test was used to determine the differences between the two groups. P values less than 0.05 were considered significant. CONCLUSION: A successful caries prevention programme started at the age of six years results in reduction of upper and lower arch crowding in the early permanent dentition. PMID- 20359274 TI - Effects of xylitol chewing gum on salivary flow rate, pH, buffering capacity and presence of Streptococcus mutans in saliva. AB - AIM: The first studies on the use of chewing gum in dentistry were done in the 1970s. The Turku Sugar Studies, carried out between 1970 and 1973, showed the excellent anticaries properties of xylitol chewing gums. Since then, many dentists, particularly in Scandinavian countries, have studied the role of chewing xylitol-sweetened chewing gums as another preventive strategy in the control of dental caries. OBJECTIVE: To compare variations in salivary flow rate, pH, buffering capacity, and levels of Streptococcus mutans in baseline conditions and after chewing paraffin pellets or xylitol chewing gum in children between the ages of 6 and 12 years who eat lunch in a school canteen. MATERIALS AND METHODS: The study sample consisted of 90 children divided into 2 study groups, and a control group. The children ate lunch at the canteen of the Escultor Ortells state school in the town of Vila-real (Castellon, Spain). The baseline data recorded in the first phase of the study were compared with the data recorded in the second phase, after 15 minutes of chewing xylitol- sweetened chewing gums or paraffin pellets, depending on the study group. Salivary flow rate was measured by collecting the stimulated saliva in a graduated beaker. Levels of pH were measured using a Cyberscan pH 110 pH meter (Eutech Instruments). CRT buffer strips and the CRT bacteria test (Ivoclar-Vivadent) were used to measure buffering capacity and levels of S. mutans, respectively. RESULTS: The data obtained after sample collection were compared by means of a 1-way analysis of variance using the StatGraphics Plus statistical software package, version 5.0. Statistically significant differences were found (p<.05) when pH, buffering capacity and levels of S. mutans were compared between the 3 groups. Comparison of salivary flow rates revealed no statistically significant differences (p>.05), though salivary flow rates were higher in the groups where gum was chewed. CONCLUSION: The effect of chewing is essential to the stimulation of salivary flow and the resulting recovery of pH levels and reduction of levels of S. mutans in saliva. PMID- 20359275 TI - Effectiveness of plaque indicators and air polishing for the sealing of pits and fissures. AB - AIM: Sealing of pits and fissures is one of the most effective techniques in caries prevention: however incomplete removal of plaque debris, can cause lack of retention of the sealant. MATERIALS AND METHODS: Sixty first permanent molars were sealed for this study. The teeth were divided into four groups. All teeth were isolated with a dental dam before cleaning and coronal polishing was performed with synthetic bristles or air polishing. Disclosing solution was used to reveal plaque. Three different operators performed cleanings and sealing. RESULTS: The results show that the plaque indicator was necessary to ensure complete cleansing of pit and fissures. PROPHYflex3 was the easiest and most effective device for removing plaque and debris. Synthetic bristles failed to thoroughly cleanse the surface in most attempts. CONCLUSION: Results suggest that pits and fissures should be cleaned with a plaque indicator and air polishers before placing a sealing material to ensure complete removal of plaque from the tooth. PMID- 20359276 TI - Comparison of oral Midazolam and Midazolam-Ketamine as sedative agents in paediatric dentistry. AB - AIM: We compared the efficacy of sedation with oral Midazolam and a combination of oral Midazolam and Ketamine, used as alternatives to general anaesthesia during tooth extraction. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 30 patients aged between 3 and 9 years, who had elective tooth extraction were included in the study. Subjects in Group A (n. 15) were given 0.75 mg/kg Midazolam orally while those in Group B (n. 15) were given 0.75 mg/kg Midazolam orally+5 mg/kg ketamine. Acceptance of orally administered drugs, sedation and anxiety scores and reactions to local anaesthetic injection and tooth extraction were assessed. RESULTS: Sedation and anxiety scores in Group B were better than in Group A (p<0.05). Reactions to local anaesthetic injection and tooth extraction were very significantly less common in Group B (p<0.0001). Requirement for an additional medication was more common in Group A (p<0.05). Side effects were not observed in either group. STATISTICS: Patient demographics and time to discharge were analysed by Mann-Whitney U test, whereas Chi-square test was used to analyse compliance to sedation, anxiety and sedation scores, reaction to tooth extraction, side effects and additional drug requirement. CONCLUSION: Compared to oral Midazolam only, a combination of oral Midazolam+Ketamine resulted in better sedation and surgical comfort in children during a painful procedure such as tooth extraction. PMID- 20359277 TI - Comparative evaluation of the group of teeth with the best prediction value in the mixed dentition analysis. AB - AIM: Mixed dentition analysis allows the prediction of the tooth width of non erupted permanent canines and premolars (SPCP). It is an essential factor in treatment planning since it could predict a tooth-size to arch-length discrepancy. The aim of this study was to determine which group of permanent teeth presented the best prediction capability for the width sums of the unerupted canine and premolars in an Italian sample. MATERIALS AND METHODS: A total of 150 subjects with complete permanent dentition were selected. Their dental casts were measured to 0.01 mm with a digital caliper. Pearson correlation and T-test were used for the statistical analysis. RESULTS/STATISTICS: The combination of the sums of the four lower incisors and the first upper molars showed the best prediction capability for the SPCP in the Italian sample. Moreover new regression equations were formulated including sex and arch as additional predictor variables. In 80% of the cases estimated differences between the predicted and the actual values were smaller than 1 mm. CONCLUSION: It can be concluded that the new regression equations proposed seemed to show good accuracy. PMID- 20359278 TI - Mothers' perceptions concerning oral health of children and adolescents with Down syndrome: a qualitative approach. AB - AIM: The aim of this qualitative study was to investigate the perceptions of a group of mothers of children and adolescents with Down syndrome (DS) concerning the overall health and oral health of their children. METHODS: The information was collected interviewing in depth 19 mothers using an open-ended orientation form. To investigate the perceptions of the mothers was carried out a thematic content analysis. Two general themes were addressed: mothers' perceptions concerning the health of the child with DS and mothers' opinion on the impact of oral health on the life of the child with DS. RESULTS: According to the interviews, for the mothers, overall health and oral health entail specificities associated mainly with the absence of illness, the performance of daily activities, and feelings of well-being. Mothers tended to hold themselves accountable for their children's health status. Within the situations these women experience, many of the interviewees reported difficulties in caring for their children's oral health. CONCLUSION: Factors linked to financial constraints, time, and access to healthcare referral services hamper the search for specialised dental care for individuals with special needs. PMID- 20359279 TI - 180-day screening study for predicting the risk factors for developing acute oral Graft-versus-Host disease in paediatric patients subjected to allogenic haematopoietic stem cells transplantation. AB - AIM: In this study, 58 paediatric patients were prospectively evaluated with a number of screening studies performed between 0 and 180 days after allogenic hematopoietic stem cells transplantation (HSTC) to detect any risk factors for developing oral manifestations of acute Graft-versus-Host Disease (a-GvHD). MATERIALS AND METHODS: A total of 58 paediatric allogenic HSTC patients (37 males aged 1 to 15, and 21 females aged 4 to 18), entered the study and were observed by a trained dental team for a period of 6 months following transplantation while assuming cyclosporine, an immunosuppressive agent with a-GvHD prophylactic activity. Mean age at transplantation was 7.2 years old. Screening studies included physical examination, complete blood counts and liver function tests. Complete extraoral and intraoral clinical examinations were performed for all patients to detect oral lesions. Furthermore, some variables (sex, number of HSTC performed in the same patient, degree of HLA disparity and the positive/negative result of cytomegalovirus antigenemia test during the three months after engraftment) were investigated in the attempt to evaluate their predictive and/or diagnostic value in paediatric HSTC recipients. The resulting data were analysed with the Fisher's exact test. RESULTS: Twenty-two percent of the patients developed oral manifestations of a-GvHD. Oral symptoms frequently are the major complaints of the patients during the follow-up period. The oral changes included mucositis, erosions and/or ulcerations; xerostomia, pain and bleeding were also referred. The variables investigated for predictive and/or diagnostic value in paediatric HSTC recipients included: sex (relative risk 0.494, 95% confidence interval 0.119-2.052, P=0.1242); number of HSTC performed in the same patient (relative risk 5.4, 95% confidence interval 0759-3.843; P=0.0714); degree of HLA disparity (relative risk 0.24, 95% confidence interval 0.058-0987, P=0.0428); and the result to cytomegalovirus (CMV) antigenemia test during the three months after engraftment (relative risk 0.86, 95% confidence interval 0.273-2.712, P=1). CONCLUSION: Patients presenting two or more risk factors should be closely monitored for development of clinical oral a-GVHD, as oral complications are a significant cause of morbidity and potential mortality for children undergoing HSTC and can interfere significantly with transplant recovery. PMID- 20359280 TI - Effect of full mouth rehabilitation on the amount of Streptococcus mutans in children with Early Childhood Caries. AB - AIM: The purpose of this study is to evaluate the effect of full mouth rehabilitation on the amount of S. mutans in children with Early Childhood Caries. MATERIALS AND METHODS: Thirty-nine children between 2 and 5 years old treated under general anaesthesia participated in this study. Prior to treatment two baselines samples were collected, one of dental plaque and one of saliva. In addition, samples were obtained one week post operatively, and then three months later. In each sampling, the amount and the concentration (cfu/ml) of S. mutans were evaluated. RESULTS: The findings demonstrate that the operative procedures under general anaesthesia, significantly decrease (p<0.01) the concentration (cfu/ml) and the amount of S. mutans for at least three months. After three months, saliva concentrations and plaque colony numbers of S. mutans increased significantly in relation to one week post-operatively (p<0.01). However, none of the saliva or plaque samples collected three months following treatment reached the pretreatment levels of S. mutans in any of our subjects. CONCLUSIONS: The data indicates that full mouth rehabilitation under general anaesthesia produces a statistically significant decrease in S. mutans levels for at least three months. PMID- 20359281 TI - Craniofacial changes and treatment of the stomatognathic system in subjects with Cleidocranial dysplasia. AB - AIM: Cleidocranial dysplasia (CCD) is a rare disorder that is inherited as an autosomal genetic trait. It is characterised by defective ossification, delayed bone and tooth development, stomatognathic and craniofacial abnormalities and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. CCD is a dental disease that needs complex rehabilitation and the assistance of several specialists. In most cases, this disease precipitates towards the end of childhood with the progressive morbidity of the deciduous dentition, thus leading to edentulism at a young age and giving patients an older appearance. Several therapeutic approaches have been proposed within literature. The aim of this paper is to revise the literature on the proposed therapeutic approaches for the functional and aesthetical rehabilitation of the typical defects caused by CCD in the cephalic region, and to identify the most effective therapy currently available. CONCLUSIONS: The most effective therapeutic approach for the early treatment of the orthodontic and orthopaedic diseases in CCD patients would start with an orthopaedic treatment of the upper jaw followed by orthodontic and surgical treatments. When growth is completed a reintervention for maxillofacial surgery and the orthodontic treatment may be required. Finally, if some teeth are missing. function and aesthetics can be achieved replacing them with prosthesis. PMID- 20359282 TI - Use of laser technology in orthodontics: hard and soft tissue laser treatments. AB - AIM: Modern technology has perfected a new instrument that has become almost indispensable in modern dentistry, in accordance with the philosophy of minimally invasive therapy: the laser. The aim of this work is to evaluate the effectiveness and efficacy of laser technology to solve mucogingival problems associated with orthodontic treatment. Some laser wavelengths work both on hard and soft tissues (2780 nm, 2940 nm), other lasers, such as the 810 nm diode, have a very good surgical and haemostatic action on soft tissues and an important analgesic and biostimulating effect that can help the healing of both TMJ painful symptoms as well as the pain following active orthodontic treatment. Several cases connected to orthodontic therapy are presented. MATERIALS AND METHODS: Different laser systems (diode laser at 810 nm; Er,Cr:YSGG laser at 2780 nm; Erbium:YAG laser at 2940 nm) were used, both for soft tissue surgery and enamel etching, and for biostimulating effect. These wavelengths were used with different parameters for each case, according to international current studies in view of minimally invasive therapy. RESULTS: The cases reported showed very quick and good healing of the laser treated tissues. These treatments, necessary for the orthodontic therapy or for its completion, become extremely simple, safe and rapid and the orthodontic specialist can perform them himself. CONCLUSION: The laser technique is very effective in many operative and surgical procedures during orthodontic therapy. Further studies are however necessary to set the treatment protocols in orthodontic biostimulation. PMID- 20359283 TI - Customised Bluegrass appliance reminder therapy. Report of two cases. AB - BACKGROUND: Thumb sucking habits make up the majority of oral habits. While thumb sucking is considered normal during the first two years of life, if it is not controlled and persists beyond the preschool period it may cause deleterious effects on dentofacial structures. Reminder therapy using Bluegrass appliance has been proven successful to intercept thumb sucking habit. CASE REPORT: We present here two cases of thumb sucking habit in 7 and 10 year old children corrected by non- punitive reminder therapy using a customised Bluegrass appliance. PMID- 20359284 TI - Macaque CYP2C76 encodes cytochrome P450 enzyme not orthologous to any human isozymes. AB - Cynomolgus monkey is used in the study of drug metabolism and toxicity due to its evolutionary closeness to human as compared with other non-human primate species. However, it has become certain that drug metabolism in monkeys is different than in humans. Such species differences have not been fully investigated at a molecular level largely due to the scarcity of information on drug-metabolizing enzyme genes. In cynomolgus monkey, we have identified cDNAs for 21 kinds of cytochromes P450 (CYPs), among which CYP2C76 does not correspond to any human CYP isozymes and is partly responsible for the difference in pitavastatin metabolism between cynomolgus monkey and human. In cynomolgus monkey CYP2C76, we identified numerous genetic variants including a null genotype. Heterozygotes for this null genotype are expected to be poor metabolizers in CYP2C76-mediated drug metabolism. To provide new clues to CYP2C76 function, here, we have taken advantage of sequence information that has been recently deposited to public databases to assess the presence of CYP2C76 orthologs in primate species. In this assessment, we found the CYP2C76 cDNA sequence in rhesus monkey, and a gene sequence highly homologous to cynomolgus monkey CYP2C76 in the marmoset and orangutan genomes, raising the possibility that CYP2C76 could also play a role in these primate species. This review paper gives an overview of CYP2C76 from isolation to molecular characterization, and its implication in drug metabolism. PMID- 20359285 TI - Comparison of enzyme kinetic parameters obtained in vitro for reactions mediated by human CYP2C enzymes including major CYP2C9 variants. AB - Cytochrome P450 (CYP) 2C enzymes contribute to the metabolism of about 30% of all drugs. Known polymorphisms of the respective enzymes and drug-drug interactions have a major impact on the efficacy and safety of some CYP2C substrate drugs. In vivo - in vitro correlations including prediction of the effect of such covariates requires quantitative information on enzyme kinetics. In this article there will be a summary of the values of the Michaelis-Menten constant (K(m)), the maximal velocity (V(max)) and the intrinsic clearance (Cl(int); V(max)/K(m)) for 84 substrates (100 reactions) reported to be mediated by CYP2C9 (variant enzymes CYP2C9.1, CYP2C9.2 and CYP2C9.3), CYP2C8 and/or CYP2C19. Particularly contradictory findings for the same reactions call for some standardization in the assessment of enzyme kinetics. PMID- 20359286 TI - An update on drug interactions with the herbal medicine Ginkgo biloba. AB - Medicinal plants are gaining in popularity due to the various advantages they offer, such as fewer side-effects, better patient compliance, relatively low cost and high accessibility as well as their high acceptability due to a long history of use. There is a widespread belief among the general public that herbal preparations are "good for humans" as they are "all natural". However, the increasing use of herbal medicinal products in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be have significant public health consequences. There is little understanding or appreciation of the fact that these "all natural" preparations are actually a combination of potentially biologically active compounds already existing in marketed products in unknown quantities. Among the most popular herbal products used worldwide is Ginkgo biloba, used for the treatment of cerebral insufficiency, peripheral vascular diseases, and frequently taken for the enhancement of memory function. Although the safety of Ginkgo biloba is promising, accumulated data show evidence of significant interactions with medications, which can place individual patients at great risk. In this review, we examined the literature from 2000 to 2008 and focused on the importance of the risk of drug interactions and potential side effects when Ginkgo biloba is involved. The aim of this systematic review is to assess the clinical evidence on interactions between Ginkgo biloba and drugs. PMID- 20359287 TI - Nanoparticle-based delivery system for application of siRNA in vivo. AB - Small interfering RNAs (siRNAs) silence the expression of specific target genes by mediating RNA interference (RNAi) in mammalian cells. siRNAs have not only been widely used as a valuable tool for functional genomics research, but they also have demonstrated great potential in biomedical therapeutic applications for diseases caused by abnormal gene overexpression or mutation. One of the most important issues to overcome before full clinical application is the development of effective administration methods for siRNAs to the target tissue or cells in vivo, which is highly dependent on the delivery system. Currently, there are two major kinds of in vivo delivery systems: viral or nonviral. As one of the nonviral carrier systems, nanoparticles, combinations of liposomes and cationic polymer complexes, have exhibited improved in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated RNAi oligos, which result in more effective silencing with less cellular toxicity and immune stimulation. This review will discuss the latest advancements in nanoparticle mediated RNAi delivery systems, including nano-materials, preparation, and characteristics. In conjunction, the clinical trial cases related to the nanoparticle-siRNA complexes will be highlighted. The safety issues of nanoparticles used in vivo will also be mentioned. Finally, this review will summarize the perspectives for future applications of nanoparticle-mediated RNAi delivery systems. PMID- 20359288 TI - Evolution of the scientific literature of cytochrome P450 from 1977 to 2008. AB - This study traces the evolution of the scientific literature on cytochrome P450 (P450) published during the last 30+ years (1977-2008). Using the Web of Science, P450 articles from the Science Citation Index Expanded published from 1977 to 2008 were retrieved and analyzed. The number of P450 papers has increased from 342 articles in 1977-1978 to 2,357 in 2007-2008, and the number of contributing countries has grown from 23 countries for 1977-1978 to 76 for 2007-2008. While the USA and Japan were the most productive countries, along with several industrialized countries (e.g. UK, Germany and Canada), two Asian countries have recently joined the group of leading countries (in 2007-2008 China ranked 4th and South Korea, 7th). During 1977-2008, the number of journals publishing papers in P450 research increased more than seven-fold (7.7): 94 journals in 1977-1978 and 724 in 2007-2008; however, citation by readers (as measured by the journal impact factor) of the top-ten leading journals increased only slightly from 3.25 for 1977-1978 to 3.81 for 2007-2008. While Biochemistry & Molecular Biology and Pharmacology and Pharmacy are the two main targeted subject areas for P450 research during the period considered, there has been a gradual shift from the biophysical and biochemical fields of interest to aspects of genomics and clinical approaches. The rapid evolution of P450 research in the last 30+ years was accompanied by important changes in the landscape of the contributing countries, in the subject domains, and consequently in the scientific journals targeted by researchers. PMID- 20359289 TI - Nanoparticles for tumor targeted therapies and their pharmacokinetics. AB - Various types of nanoparticles, such as liposomes, polymeric micelles, dendrimers, superparamagnetic iron oxide crystals, and colloidal gold, have been employed in targeted therapies for cancer. Both passive and active targeting strategies can be utilized for nano-drug delivery. Passive targeting is based on the enhanced permeability and retention (EPR) effect of the vasculature surrounding tumors. Active targeting relies on ligand-directed binding of nanoparticles to receptors expressed by tumor cells. Release of loaded drugs from nanoparticles may be controlled in response to changes in environmental condition such as temperature and pH. Biodistribution profiles and anticancer efficacy of nano-drugs in vivo would be different depending upon their size, surface charge, PEGylation and other biophysical properties. This review focuses on the recent development of nanoparticles for tumor targeted therapies, including physicochemical properties, tumor targeting, control of drug release, pharmacokinetics, anticancer efficacy and safety. Future perspectives are discussed as well. PMID- 20359290 TI - New prospects for nelfinavir in non-HIV-related diseases. AB - Nelfinavir (Viracept) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes. PMID- 20359291 TI - Treating asthma as a neuroelectrical disorder. AB - The trend in asthma therapy for the last two decades has been based on the suppression of inflammation and bronchodilation via adrenergic agonism or cholinergic antagonism. These strategies help to control asthmatic symptoms but do not lead to a cure. Substantial populations of patients may still have poorly managed symptoms and suffer a decline in quality of life due to the disease. Reversible airflow obstruction and nonspecific airway reactivity are the key features of asthma. Inflammatory changes do not correlate always with symptoms in asthma patients. It is our opinion that the primary defect in asthma is cell membrane excitation-bronchoconstriction and reactivity-rather than inflammation. Our research, clinical experience and the accumulated evidence from medical literature strongly suggest that controlling other excitatory mechanisms such as voltage-gate sodium channel and glutamate receptors in the central nervous system and lung tissue could lead to more effective and safer strategies for asthma prevention and treatment. PMID- 20359292 TI - A new protocol for functional analysis of adipogenesis using reverse transfection technology and time-lapse video microscopy. AB - Since the worldwide increase in obesity represents a growing challenge for healthcare systems, research focusing on fat cell metabolism has become a focal point of interest. Here, we describe a small interfering RNA (siRNA)-technology based screening method to study fat cell differentiation in human primary preadipocytes that could be further developed towards an automated middle throughput screening procedure. First, we established optimal conditions for the reverse transfection of human primary preadipocytes demonstrating that an efficient reverse transfection of preadipocytes is technically feasible. Aligning the processes of reverse transfection and fat cell differentiation utilizing peroxisome proliferator-activated receptor gamma (PPAR gamma)-siRNA, we showed that preadipocyte differentiation was suppressed by knock-down of PPAR gamma, the key regulator of fat cell differentiation. The use of fluorescently labelled fatty acids in combination with fluorescence time-lapse microscopy over a longer period of time enabled us to quantify the PPAR gamma phenotype. Additionally, our data demonstrate that reverse transfection of human cultured preadipocytes with TIP60 (HIV-1 Tat-interacting protein 60)-siRNA lead to a TIP60 knock-down and subsequently inhibits fat cell differentiation, suggesting a role of this protein in human adipogenesis. In conclusion, we established a protocol that allows for an efficient functional and time-dependent analysis by quantitative time-lapse microscopy to identify novel adipogenesis-associated genes. PMID- 20359293 TI - Effect of budesonide on TGF-beta1-enhanced VEGF production by lung fibroblasts. AB - VEGF (vascular endothelial growth factor) is a potent proangiogenic cytokine, and vascular change is one of the characteristic features of airway remodelling. Since the glucocorticoids have shown antifibrosis properties, we sought to investigate whether budesonide, a widely used glucocorticoid in clinical practice, could attenuate TGF-beta1 (transforming growth factor-beta1)-induced VEGF production by HFL-1 (human lung fibroblasts). HFL-1 fibroblasts were treated with various concentrations of budesonide (10(-11) M, 10(-9) M and 10(-7) M) in the absence or presence of TGF-beta1. Postculture media were collected for ELISA of VEGF at the indicated times. The cell lysates were subjected to Western blotting analysis to test TGF-beta1/Smad and MAP (mitogen-activated protein) kinase signalling activation, respectively. The results suggested that budesonide pretreatment reduced the significant increase of VEGF release induced by TGF beta1 in HFL-1 fibroblasts in a dose-dependent manner, and suppressed the increase of phospho-Smad3 and phosphor-ERK (extracellular signal-regulated kinase) protein levels. In conclusion, budesonide may reduce TGF-beta1-induced VEGF production in the lung, probably through the Smad/ERK signalling pathway and, thus, may provide new sight into the molecular mechanism underlying glucocorticoid therapy for airway inflammatory diseases. PMID- 20359294 TI - A Cre-based double fluorescence indicator system for monitoring cell fusion events and selection of fused cells. AB - We have established an in vitro Cre/loxP-based assay for monitoring cell fusion events that specifically traces the transport of cytoplasm from one cell to its fusion partner. Cells with a double fluorescence vector indicate fusion with cells expressing Cre recombinase by switching expression from red to green fluorescent protein through a Cre-mediated recombination event that simultaneously activates puromycin-acetyltransferase expression. This strategy allows for both the observation and puromycin selection of indicator cells that have undergone fusion with a Cre recombinase-expressing partner. A fusion protein of Cre with estrogen receptor (ER) can be used to control Cre recombinase activity through the tamoxifen-induced translocation of the Cre-ER fusion protein to the nucleus. Here we have established a new methodology that not only allows the monitoring of the transport of cellular contents, but also enables the purification of fused cells using puromycin. PMID- 20359295 TI - An agarose spot assay for chemotactic invasion. AB - The directed motility of cells toward the source of a soluble chemical (chemotaxis) plays a role in events ranging from immune function to cancer progression. Numerous chemotaxis assays are commonly employed, yet none provides an optimal combination of the relevant parameters. The ideal chemotaxis assay for use in the analysis of cells crawling across a planar surface should be cost effective, simple to perform, and suitable for high-throughput multiplexing, as well as permit alteration of experimental conditions during cell motility. Here we describe a novel chemotaxis assay based upon the invasion of cells into agarose spots into which chemoattractants are suspended. Our studies demonstrate that this system assays chemotaxis and not chemokinesis, and provide proof-of principle for drug screening studies as well as analysis through high-resolution cellular imaging. PMID- 20359296 TI - Enhanced fluorescence imaging in chlorophyll-suppressed tobacco tissues using virus-induced gene silencing of the phytoene desaturase gene. AB - Fluorescence imaging in plants is unusually challenging because of the large amounts of photosynthetic pigments contained in green plant tissues. For example, chlorophyll can obstruct the penetration of light and has high levels of autofluorescence at wavelengths that are often used for fluorescence imaging. Until now, mostly confocal laser scanning microscopy or the use of non-green parts of the plants, typically roots, have been used to overcome these limitations. We constructed tobacco (Nicotiana attenuata) plants expressing GFP sporamin fusion polypeptide in their vascular tissues. As expected, it was not possible to visualize GFP fluorescence in tobacco leaves or stems using a stereomicroscope and filters specific for GFP detection; however, GFP fluorescence was readily detectable when virus-induced gene silencing (VIGS) was used to transiently silence the phytoene desaturase (PDS) gene in order to bleach chlorophyll-containing tissues. This method is an inexpensive alternative to confocal laser scanning microscopy for the detection of GFP fusion proteins or promoter-GFP reporter fusions in plant leaves. PMID- 20359297 TI - A micro-incubator for cell and tissue imaging. AB - A low-cost micro-incubator for imaging dynamic processes in living cells and tissues has been developed. This micro-incubator provides a tunable environment that can be altered to study responses of cell monolayers for several days as well as relatively thick tissue samples and tissue-engineered epithelial tissues in experiments lasting several hours. Samples are contained in a sterile cavity closed by a gas-permeable membrane. The incubator can be positioned in any direction and used on an inverted or upright microscope. Temperature is regulated using a Peltier module controlled by a sensor positioned close to the sample, enabling compensation for any changes in temperature. Rapid changes in a sample's surrounding environment can be achieved due to the fast response of the Peltier module. These features permit monitoring of sample adaptation to induced environmental changes. PMID- 20359298 TI - A new technique for obtaining whole pathogen transcriptomes from infected host tissues. AB - We propose a novel experimental approach based on coincidence cloning for analyzing sequences of bacterial intracellular pathogens specifically transcribed in affected tissues. Co-denaturation and co-renaturation of excess bacterial genomic DNA with the cDNA prepared on total RNA of the infected tissue allows one to select the bacterial fraction of the cDNA sample. We used this technique for preparing and characterizing the Mycobacterium tuberculosis cDNA pool, representing the transcriptome of infected mouse lungs in the chronic phase of infection. A cDNA pool enriched in fragments of mycobacterial cDNA was analyzed by the high-throughput 454 sequencing procedure. We demonstrated that its composition corresponded to what can be expected in the chronic phase of infection and, after the adaptation of M. tuberculosis to the host immune system, was characterized by an active lipid metabolism and switched from aerobic to anaerobic respiration. The technique is universal and requires no prior knowledge of the pathogen genome sequence. Pools of transcribed sequences obtained by this technique retain the main characteristics of the genome-wide gene transcription pattern within infected tissue, and can be used for in vivo analysis of gene expression of a wide spectrum of infection agents, such as viruses, bacteria, and protista. PMID- 20359299 TI - A proximity ligation assay using transiently transfected, epitope-tagged proteins: application for in situ detection of dimerized receptor tyrosine kinases. AB - The development of small molecule and antibody inhibitors targeting the interaction of receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), is of high pharmacological and biological interest. Unfortunately, conventional biochemical techniques using cell or tissue lysates and co-immunoprecipitation experiments to investigate EGFR dimerization are not always conclusive. Here we describe a series of technical and biological validation experiments demonstrating the utility of a proximity ligation assay (PLA)-based methodology for in situ visualization and quantification of ligand dependent EGFR receptor dimerization in intact cells. Using the PLA approach combined with a universally applicable epitope tagging strategy, we detected EGFR dimers in cells transiently co-expressing FLAG-tagged and MYC-tagged human EGFRs. Our data strongly suggest that PLA can be used to detect ligand-dependent EGFR dimerization and this signal is generated in a protein interaction-based manner, rather than solely due to proximity of target proteins. This application represents a generalized RTK expression strategy for protein-interaction analysis in a transient expression system where antibody epitopes are not known or not unique enough to discriminate between interaction partners. This assay also holds promise as a general RTK dimerization screening tool in tissue specimens to identify potential dimerization inhibitors with clinical relevance. PMID- 20359300 TI - Linear measurement of cell contraction in a capillary collagen gel system. AB - Three-dimensional collagen gel contraction is the standard assay utilized for functionally quantifying a variety of cell types, in particular smooth muscle cells (SMCs) and myofibroblasts. Here, we have developed a method to effectively reduce the three-dimensional parameters of the standard collagen gel into a single, linear measurement. Cell/collagen suspensions that are cast into glass capillary tubes provide several advantages over the well plate format, such as eliminating the need for digital imaging equipment and software to quantify the amount of cellular contraction. In addition, capillary tube gels require significantly fewer cells and far less reagents than standard methods. PMID- 20359301 TI - Antibody validation. AB - Antibodies are among the most frequently used tools in basic science research and in clinical assays, but there are no universally accepted guidelines or standardized methods for determining the validity of these reagents. Furthermore, for commercially available antibodies, it is clear that what is on the label does not necessarily correspond to what is in the tube. To validate an antibody, it must be shown to be specific, selective, and reproducible in the context for which it is to be used. In this review, we highlight the common pitfalls when working with antibodies, common practices for validating antibodies, and levels of commercial antibody validation for seven vendors. Finally, we share our algorithm for antibody validation for immunohistochemistry and quantitative immunofluorescence. PMID- 20359303 TI - Concordance among digital gene expression, microarrays, and qPCR when measuring differential expression of microRNAs. AB - Profiling microRNA (miRNA) expression is of widespread interest given the critical role of miRNAs in many cellular functions. Profiling can be achieved via hybridization-based (microarrays), sequencing-based, or amplification-based (quantitative reverse transcription-PCR, qPCR) technologies. Among these, microarrays face the significant challenge of accurately distinguishing between mature and immature miRNA forms, and different vendors have developed different methods to meet this challenge. Here we measure differential miRNA expression using the Affymetrix, Agilent, and Illumina microarray platforms, as well as qPCR (Applied Biosystems) and ultra high-throughput sequencing (Illumina). We show that the differential expression measurements are more divergent when the three types of microarrays are compared than when the Agilent microarray, qPCR, and sequencing technology measurements are compared, which exhibit a good overall concordance. PMID- 20359302 TI - Quantifying the relative amount of mouse and human DNA in cancer xenografts using species-specific variation in gene length. AB - Human cancer cell lines and xenografts are valuable samples for whole-genome sequencing of human cancer. Tumors can be maintained by serial xenografting in athymic (nude) or severe combined immunodeficient (SCID) mice. In the current study, we developed a molecular assay to quantify the relative contributions of human and mouse in mixed DNA samples. The assay was designed based on deletion/insertion variation between human and mouse genomes. The percentage of mouse DNA was calculated according to the relative peak heights of PCR products analyzed by capillary electrophoresis. Three markers from chromosomes 9 and 10 accurately predicted the mouse genome ratio and were combined into a multiplex PCR reaction. We used the assay to quantify the relative DNA amounts of 93 mouse xenografts used for a recently reported integrated genomic analysis of human pancreatic cancer. Of the 93 xenografts, the mean percentage of contaminating mouse DNA was 47%, ranging from 17% to 73%, with 43% of samples having >50% mouse DNA. We then comprehensively compared the human and mouse genomes to identify 370 additional candidate gene loci demonstrating human-mouse length variation. With increasing whole-genome sequencing of human cancers, this assay should be useful to monitor strategies to enrich human cancer cells from mixed human-mouse cell xenografts. Finally, we discuss how contaminating mouse DNA affects next generation DNA sequencing. PMID- 20359304 TI - An efficient stress-free strategy to displace stable bacterial plasmids. AB - A key stage in determining the phenotype(s) conferred by a plasmid is its displacement, or 'curing,' to create a plasmid-free strain. However, many plasmids are very stable, not only because they contain multiple replicons, but also because they can encode post-segregational killing systems that reduce the viability of plasmid-free segregants. We have developed an efficient curing strategy that involves combining key regions of the replicons and the post segregational killing loci into an unstable cloning vector carrying sacB, which confers sensitivity to sucrose. Targeting plasmids of both the F family of Escherichia coli and the broad-host-range IncP-1 family, we demonstrated displacement of susceptible resident plasmids from all clones tested. Growth on sucrose allowed the isolation of many clones without either plasmid. This strategy is highly efficient and avoids the stress of inducing and surviving the effects of post-segregational killing systems or other lethal gene products. PMID- 20359305 TI - A modified feeding RNAi method for simultaneous knock-down of more than one gene in Caenorhabditis elegans. AB - RNA interference (RNAi) is a commonly used technique for reverse genetic approaches in Caenorhabditis elegans. Feeding RNAi is the most convenient and inexpensive method for performing genome-wide RNAi screens. However, it has been reported that knock-down of two genes (double RNAi) by feeding RNAi using a mixture of bacteria that each contained one dsRNA species produced poor results. To overcome this problem of inefficiency, we designed and tested a double feeding RNAi method using a single RNAi construct containing two gene fragments. From experiments with three different sets of genes, we found that the new double RNAi method consistently produced significantly enhanced double knock-down phenotypes. The double feeding RNAi approach described here provides a method to consistently examine phenotypes caused by depletion of more than one gene in C. elegans. PMID- 20359306 TI - Direct PCR amplification and sequencing of specimens' DNA from preservative ethanol. AB - DNA extraction is the first step in many molecular biology protocols. However, we hypothesized that DNA from a preserved specimen can leak into its preservative medium, allowing the medium itself to be directly PCR-amplified. We successfully tested this idea on mescal-the alcoholic beverage famous for the "worm" (a caterpillar) that is placed in the bottle of many brands-and indeed obtained amplifiable quantities of caterpillar DNA. We then successfully amplified and sequenced DNA from the 95% ethanol preservative of 70 freshly collected specimens and 7 archival specimens 7-10 years old. These results suggest that DNA extraction is a superfluous step in many protocols and that preservative ethanol can be used as a source of genetic material for non-invasive sampling or when no tissue specimen is left for further DNA analyses. PMID- 20359307 TI - A lens-specific co-injection marker for medaka transgenesis. AB - Recent advances in generating transgenic fish have improved the efficiency of germline transmission and enabled the generation of large numbers of transgenic animals. A suitable co-injection marker may help facilitate the preselection of transgenic embryos. For this purpose, a lens-specific marker appears to be a suitable candidate since the lens is a well-defined tissue that is easily accessible for examination of reporter gene expression. We constructed reporter vectors including the mouse gamma-F crystallin (mgammaF-Cry) promoter, which drives high levels of lens-specific heterologous expression of the reporter gene and thereby enables easy sorting of transgenic fish. PMID- 20359308 TI - An assessment of adverse effects of antiretroviral therapy on the development of HIV positive children by observation of dental mineralization chronology. AB - BACKGROUND: The difference between dental age (DA) and chronological age (CA) indicates an advance or delay in comparison with the normal standard. Considering that DA has a very close correlation with CA in a developing child, this study aimed to investigate the relationship between the effects of antiretroviral therapy on the development of HIV positive children, by observing the timing of dental mineralization. METHODS: A retrospective examination was made of the medical records and dental panoramic radiographs of 50 HIV-positive pediatric patients, aged 37-168 months of age. Through these radiographs, their DA was estimated and compared with their CA. RESULTS: The mean DA was significantly lower than the mean CA in the entire studied sample (P < 0.01). There was a statistical difference between children who received antiretroviral drugs and those who used no drugs (P = 0.02), i.e. the non-treated individuals presented practically no difference between CA and DA, while the treated patients showed a difference of 10.67 months. CONCLUSION: We conclude that the DA of HIV infected children was delayed when compared to the CA, and there was a positive association between the use of antiretroviral therapy and a delay in the chronology of dental mineralization in the sample. PMID- 20359309 TI - Podoplanin expression in human tooth germ tissues and cystic odontogenic lesions: an immunohistochemical study. AB - BACKGROUND: Podoplanin expression was described in mouse tooth germ and apical bud cells. The aim of this study was to analyse the podoplanin expression of human tooth germ tissues, adult teeth and odontogenic lesions immunohistochemically. STUDY DESIGN: Nine human tooth germ biopsies and seven healthy permanent teeth extracted for orthodontic reasons were examined. Anti podoplanin (D2-40) reactivity was investigated immunohistochemically. Five well defined cystic odontogenic lesions (10 radicular cysts, 10 follicular cysts, three keratocystic odontogenic tumours, five ameloblastomas, and two adenomatoid odontogenic tumours) were analysed simultaneously. RESULTS: Podoplanin expression was detected in the majority of epithelial and ecto-mesenchymal cells of human tooth germ tissues, odontoblasts and superficial dental pulp fibroblasts of permanent teeth. Cystic odontogenic lesions revealed positive reactions predominantly at the invasion front edge within basal epithelial layers. CONCLUSION: Podoplanin appears to be involved in the orthologic and pathologic processes of the formation of elongated cell extensions and odontoblastic fibers, in the epithelial-mesenchymal transition and local invasion during tooth germ development as well as in both reactive and neoplastic odontogenic cystic lesions. PMID- 20359310 TI - Mast cells in periapical lesions: potential role in their pathogenesis. AB - OBJECTIVE: The aim of this study was to qualitatively and semi-quantitatively analyze mast cells in periapical lesions. MATERIALS AND METHODS: Biopsy specimens of 96 periapical lesions were stained with hematoxylin-eosin, histochemical Giemsa and immunohistochemical CD 117 (C kit) antibody. Mast cell count below 100 mast cells on 1000 fields of high power magnification was noted as 'negative', 101-400 as 'mild', 401-800 cells as 'moderate', and over 800 cells as 'severe'. RESULTS: Mast cells are found in 68 (70.8%) lesions. The presence of mast cells was greater in cysts than in granulomas (P < 0.0028). There was no difference in semi-quantitative expression of CD 117 in granulomas and cysts (P > 0.05). Mast cells were placed in both: inflammatory infiltrate and in fibroblastic areas of periapical lesions, and their presence was most frequently mild to moderate. CONCLUSIONS: The findings of present study could suggest a role of mast cells in regulation of cellular immune mechanisms in periapical lesions, balancing between alterative and reparatory processes in inflamed periapical tissue. PMID- 20359311 TI - Human oral keratinocyte E-cadherin degradation by Candida albicans and Candida glabrata. AB - BACKGROUND: E-cadherin (E-Cad) is a 120-kDa adhesive protein found in adherens junctions of the digestive tract epithelium. We tested the ability of two Candida strains to degrade human E-Cad in the Candida virulence factor perspective. MATERIALS AND METHODS: We set out to study oral mucosal E-Cad degradation by clinical and reference strains of Candida albicans and Candida glabrata. We also included hyphal and secreted aspartic proteinase (Sap) mutants of C. albicans to test the effect of yeast/hyphal transition on the ability to degrade E-Cad. The tests were performed at pH 4 and pH 6 to determine the effect of local tissue acidity on the activation of Saps. The C. albicans strains used were: CCUG 32723; clinical strain SC5314 which is known to be strongly invasive; hyphal mutants of SC5314: HLC52 (efg1/efg1), HLC54 (cph1/cph1 efg1/efg1) and JKC19 (cph1/cph1); clinical strain B1134; Sap 1-3 and Sap 4-6 mutants of SC5314. The C. glabrata strains used were ATCC 90030, and the clinical strains 5WT and G212. RESULTS: The sonicated yeast cells of C. albicans JKC19 and SC5314, both in hyphal form, degraded E-Cad at pH 4. The 10x concentrated growth media of the strains HLC-52, HLC-54, 32723 and B1134; all in yeast form, caused degradation at pH 4, HLC-52 and HLC-54 also at pH 6. The C. glabrata strains did not degrade E-Cad. CONCLUSIONS: pH is a strain dependent triggering factor in activating yeast or hyphal form related Candida Saps in degrading epithelial cell associated E-Cads. PMID- 20359312 TI - Polymorphisms in the apoptosis-associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population. AB - BACKGROUND: Our aim was to measure the relationship of FAS (-1377G>A and 670A>G), FASL (-844C>T) gene variants and risk of oral cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the FAS and FASL polymorphisms in 294 oral squamous cell carcinoma (OSCC), 53 oral submucous fibrosis (OSF), and 84 oral leukoplakia (OL) patients, as well as in 333 healthy controls. A standardized questionnaire was applied to collect demographic data, and potential confounding factors. JMP statistical software was used to analyze the association. RESULTS: FAS and FASL polymorphisms were not correlated with OSCC development or the malignant potential of OL by simple and multivariate logistic regression. However, a two- to fourfold difference in the risks of betel quid chewing, alcohol consumption, and smoking on OSCC development were observed between participants with different FAS polymorphisms. FAS polymorphisms were significantly correlated with the malignant potential of OSF. Multivariate logistic regression analysis indicated that FAS A(-1377)-G(-670) vs. G(-1377)-A( 670) haplotype (OR = 2.26, 95% CI = 1.16-4.41) was correlated with the malignant potential of OSF. CONCLUSIONS: We suggest that FAS and FASL polymorphisms are not significantly correlated with OSCC development or malignant potential of OL. The impact of substance usage on OSCC development could be differentiated by FAS polymorphisms. FAS A(-1377)-G(-670) haplotype may play a role in the malignant potential of OSF. PMID- 20359313 TI - Non-invasive ventilation in acute respiratory failure related to 2009 pandemic Influenza A/H1N1 virus infection. PMID- 20359314 TI - Disaster medicine: the caring contradiction. AB - The nature of mankind is a concern for those in need. Disasters, both natural and manmade, have been with us since the beginning of recorded history but media coverage of them is a relatively new phenomenon. When these factors come together, there is great potential to both identify and serve the sick and injured. However, the mass media by its nature tends to enhance the humanistic aspect of rescue while minimizing the practical problems involved. We describe a recent scenario in Haiti that puts some of these complications into a practical perspective. PMID- 20359315 TI - Can heterogeneity in ventilation be good? AB - Selection of the optimal positive end-expiratory pressure (PEEP) to avoid ventilator-induced lung injury in patients under mechanical ventilation is still a matter of debate. Many methods are available, but none is considered the gold standard. In the previous issue of Critical Care, Zhao and colleagues applied a method based on electrical impedance tomography to help select the PEEP that minimized ventilation inhomogeneities. Though promising when alveolar collapse and overdistension are present, this method might be misleading in patients with normal lungs. PMID- 20359316 TI - Pinpointing key mechanisms in Alzheimer's disease development. AB - van Exel and colleagues present an elegant study testing relationships between vascular and inflammatory traits and the risk of Alzheimer's disease (AD) development. They compared middle-aged offspring of AD cases with similar offspring of nondemented parents and observed greater inflammatory response to challenge and increased hypertension in those at high genetic risk. These observations join a growing body of evidence implicating inflammation/innate immunity as a crucial component in disease development. Recent discoveries of new risk genes for Alzheimer's disease also implicate innate immunity and to some extent vascular health as potentially important in pathogenesis. Further identification and refinement of putative disease mechanisms is likely as the genetic architecture of AD is uncovered through current large-scale association and sequencing studies. PMID- 20359317 TI - Genome of a songbird unveiled. AB - An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena. PMID- 20359318 TI - Robust and specific inhibition of microRNAs in Caenorhabditis elegans. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of numerous target genes. Yet, while hundreds of miRNAs have been identified, little is known about their functions. In a recent report published in Silence, Zheng and colleagues demonstrate a technique for robust and specific knockdown of miRNA expression in Caenorhabditis elegans using modified antisense oligonucleotides, which could be utilized as a powerful tool for the study of regulation and function of miRNAs in vivo. PMID- 20359319 TI - Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature. AB - BACKGROUND: Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in GFAP that cause this disease, cases of adult-onset ALX have been increasingly reported. CASE PRESENTATION: We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the GFAP gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX. CONCLUSION: The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the GFAP gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX. PMID- 20359320 TI - Histone variant macroH2A1 deletion in mice causes female-specific steatosis. AB - BACKGROUND: Vertebrate heterochromatin contains a non-allelic variant of the histone H2A called macroH2A1, which has the characteristic of being three times the size of the canonical H2A. The macroH2A1 C-terminal extension can recruit onto chromatin the poly-ADP-ribose polymerase (PARP)1, which is crucial for DNA repair. This led to the speculation that macroH2A1 could be essential for genome surveillance; however, no experimental evidence supported this hypothesis. Because macroH2A1 has been found to be enriched on the inactive X-chromosome in females, it is thought to play a role in sex chromosome dosage compensation through its ability to regulate gene expression. However, more genetic data are needed to further understand the function of macroH2A1 in mammals. RESULTS: Deletion of the murine gene H2afy, which encodes for macroH2A1, resulted in lipid accumulation in liver. Hepatic steatosis caused by H2afy disruption occurred specifically in homozygous mutant females. The metabolic disorder constantly affected half of the number of homozygote females. Given the mixed genetic background of the mutants, an unreported genetic modifier is likely to influence the penetrance of the phenotype. In addition, the X-linked thyroxine-binding globulin (Tbg) gene was specifically upregulated in steatotic livers. Chromatin immunoprecitation indicated that macroH2A1 is enriched at the Tbg promoter in wild-type female animals, indicating that increased Tbg expression in H2afy null mutants is likely to be a direct consequence of the absence of macroH2A1. Furthermore, male mice, which are not prone to the metabolic disorder, had a reduced level of macroH2A1 incorporated into the Tbg promoter. CONCLUSIONS: Because TBG is the main carrier of the thyroid hormone T4, which regulates energy metabolism, we propose that overexpression of TBG is responsible for the fat accumulation observed in H2afy-deficient liver. Moreover, our results suggest that the sexual dimorphism of the steatotic phenotype is probably due to the different incorporation of macroH2A1 in males and females. In combination with previous studies, our data demonstrate a role for macroH2A1 in regulating homeostasis in a sex-dependent manner, subject to genetic background. PMID- 20359321 TI - Optimized design and data analysis of tag-based cytosine methylation assays. AB - Using the type III restriction-modification enzyme EcoP15I, we isolated sequences flanking sites digested by the methylation-sensitive HpaII enzyme or its methylation-insensitive MspI isoschizomer for massively parallel sequencing. A novel data transformation allows us to normalise HpaII by MspI counts, resulting in more accurate quantification of methylation at >1.8 million loci in the human genome. This HELP-tagging assay is not sensitive to sequence polymorphism or base composition and allows exploration of both CG-rich and depleted genomic contexts. PMID- 20359322 TI - Inhibiting miRNA in Caenorhabditis elegans using a potent and selective antisense reagent. AB - BACKGROUND: Antisense reagents can serve as efficient and versatile tools for studying gene function by inhibiting nucleic acids in vivo. Antisense reagents have particular utility for the experimental manipulation of the activity of microRNAs (miRNAs), which are involved in the regulation of diverse developmental and physiological pathways in animals. Even in traditional genetic systems, such as the nematode Caenorhabditis elegans, antisense reagents can provide experimental strategies complementary to mutational approaches. Presently no antisense reagents are available for inhibiting miRNAs in the nematode C. elegans. RESULTS: We have developed a new class of fluorescently labelled antisense reagents to inhibit miRNAs in developing worms. These reagents were synthesized by conjugating dextran with 2'-O-methyl oligoribonucleotide. The dextran-conjugated antisense reagents can be conveniently introduced into the germline of adult hermaphrodites and are transmitted to their progeny, where they efficiently and specifically inhibit a targeted miRNA in different tissues, including the hypodermis, the vulva and the nervous system. We show that these reagents can be used combinatorially to inhibit more than one miRNA in the same animal. CONCLUSION: This class of antisense reagents represents a new addition to the toolkit for studying miRNA in C. elegans. Combined with numerous mutants or reporter stains available, these reagents should provide a convenient approach to examine genetic interactions that involve miRNA, and may facilitate studying functions of miRNAs, especially ones whose deletion strains are difficult to generate.See related research article: http://jbiol.com/content/9/3/20. PMID- 20359323 TI - A comparison of SNPs and microsatellites as linkage mapping markers: lessons from the zebra finch (Taeniopygia guttata). AB - BACKGROUND: Genetic linkage maps are essential tools when searching for quantitative trait loci (QTL). To maximize genome coverage and provide an evenly spaced marker distribution a combination of different types of genetic marker are sometimes used. In this study we created linkage maps of four zebra finch (Taeniopygia guttata) chromosomes (1, 1A, 2 and 9) using two types of marker, Single Nucleotide Polymorphisms (SNPs) and microsatellites. To assess the effectiveness and accuracy of each kind of marker we compared maps built with each marker type separately and with both types of marker combined. Linkage map marker order was validated by making comparisons to the assembled zebra finch genome sequence. RESULTS: We showed that marker order was less reliable and linkage map lengths were inflated for microsatellite maps relative to SNP maps, apparently due to differing error rates between the two types of marker. Guidelines on how to minimise the effects of error are provided. In particular, we show that when combining both types of marker the conventional process of building linkage maps, whereby the most informative markers are added to the map first, has to be modified in order to improve map accuracy. CONCLUSIONS: When using multiple types and large numbers of markers to create dense linkage maps, the least error prone loci (SNPs) rather than the most informative should be used to create framework maps before the addition of other potentially more error prone markers (microsatellites). This raises questions about the accuracy of marker order and predicted recombination rates in previous microsatellite linkage maps which were created using the conventional building process, however, provided suitable error detection strategies are followed microsatellite-based maps can continue to be regarded as reasonably reliable. PMID- 20359324 TI - Evolution of a cluster of innate immune genes (beta-defensins) along the ancestral lines of chicken and zebra finch. AB - BACKGROUND: Avian beta-defensins (AvBDs) represent a group of innate immune genes with broad antimicrobial activity. Within the chicken genome, previous work identified 14 AvBDs in a cluster on chromosome three. The release of a second bird genome, the zebra finch, allows us to study the comparative evolutionary history of these gene clusters between from two species that shared a common ancestor about 100 million years ago. RESULTS: A phylogenetic analysis of the beta-defensin gene clusters in the chicken and the zebra finch identified several cases of gene duplication and gene loss along their ancestral lines. In the zebra finch genome a cluster of 22 AvBD genes were identified, all located within 125 Kbp on chromosome three. Ten of the 22 genes were found to be highly conserved with orthologous genes in the chicken genome. The remaining 12 genes were all located within a cluster of 58 Kbp and are suggested to be a result of recent gene duplication events that occurred after the galliformes- passeriformes split (G-P split). Within the chicken genome, AvBD6 was found to be a duplication of AvBD7, whereas the gene AvDB14 seems to have been lost along the ancestral line of the zebra finch. The duplicated beta-defensin genes have had a significantly higher accumulation of non-synonymous over synonymous substitutions compared to the genes that have not undergone duplication since the G-P split. The expression patterns of avian beta-defensin genes seem to be well conserved between chicken and zebra finch. CONCLUSION: The genomic comparisons of the beta-defensins gene clusters of the chicken and zebra finch illuminate the evolutionary history of this gene complex. Along their ancestral lines, several gene duplication events have occurred in the passerine line after the galliformes-passeriformes split giving rise to 12 novel genes compared to a single duplication event in the galliformes line. After the duplication events, the duplicated genes have been subject to a relaxed selection pressure compared to the non-duplicated genes, thus supporting models of evolution by gene duplication. PMID- 20359325 TI - Digital gene expression analysis of the zebra finch genome. AB - BACKGROUND: In order to understand patterns of adaptation and molecular evolution it is important to quantify both variation in gene expression and nucleotide sequence divergence. Gene expression profiling in non-model organisms has recently been facilitated by the advent of massively parallel sequencing technology. Here we investigate tissue specific gene expression patterns in the zebra finch (Taeniopygia guttata) with special emphasis on the genes of the major histocompatibility complex (MHC). RESULTS: Almost 2 million 454-sequencing reads from cDNA of six different tissues were assembled and analysed. A total of 11,793 zebra finch transcripts were represented in this EST data, indicating a transcriptome coverage of about 65%. There was a positive correlation between the tissue specificity of gene expression and non-synonymous to synonymous nucleotide substitution ratio of genes, suggesting that genes with a specialised function are evolving at a higher rate (or with less constraint) than genes with a more general function. In line with this, there was also a negative correlation between overall expression levels and expression specificity of contigs. We found evidence for expression of 10 different genes related to the MHC. MHC genes showed relatively tissue specific expression levels and were in general primarily expressed in spleen. Several MHC genes, including MHC class I also showed expression in brain. Furthermore, for all genes with highest levels of expression in spleen there was an overrepresentation of several gene ontology terms related to immune function. CONCLUSIONS: Our study highlights the usefulness of next generation sequence data for quantifying gene expression in the genome as a whole as well as in specific candidate genes. Overall, the data show predicted patterns of gene expression profiles and molecular evolution in the zebra finch genome. Expression of MHC genes in particular, corresponds well with expression patterns in other vertebrates. PMID- 20359326 TI - Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals. AB - BACKGROUND: The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch. RESULTS: A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in CASP3 and BACE, and a large genomic expansion of acrosin. CONCLUSIONS: We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions. PMID- 20359327 TI - Evolution of the MAGUK protein gene family in premetazoan lineages. AB - BACKGROUND: Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK) are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki, an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa. RESULTS: Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki. However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria) is quite similar, except for one class that is missing in Trichoplax, while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI. Furthermore, M. brevicollis has suffered a lineage specific diversification. CONCLUSIONS: The diversification of the MAGUK protein gene family occurred, most probably, prior to the divergence between Metazoa+choanoflagellates and the Capsaspora+Ministeria clade. A MAGI-like, a DLG like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK diversification. This study highlights the importance of generating enough genome data from the broadest possible taxonomic sampling, in order to fully understand the evolutionary history of major protein gene families. PMID- 20359328 TI - Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch. AB - BACKGROUND: Steroids are small molecule hormones derived from cholesterol. Steroids affect many tissues, including the brain. In the zebra finch, estrogenic steroids are particularly interesting because they masculinize the neural circuit that controls singing and their synthesis in the brain is modulated by experience. Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors. Based on these analyses, we also investigated neural expression of a cholesterol transport protein gene in the context of song neurobiology. RESULTS: We present sequence based analysis of twenty steroid-related genes using the genome assembly and other resources. Generally, zebra finch genes showed high homology to genes in other species. The diversity of steroidogenic enzymes and receptors may be lower in songbirds than in mammals; we were unable to identify all known mammalian isoforms of the 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase families in the zebra finch genome assembly, and not all splice sites described in mammals were identified in the corresponding zebra finch genes. We did identify two factors, Nobox and NR1H2-RXR, that may be important for coordinated transcription of multiple steroid-related genes. We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR). We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed. Also, transcription of TSPO, but not StAR, may be regulated by the experience of hearing song. CONCLUSIONS: The genes required for estradiol synthesis and action are represented in the zebra finch genome assembly, though the complement of steroidogenic genes may be smaller in birds than in mammals. Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated. Integration of genomic and neuroanatomical analyses will continue to provide insights into the evolution and function of steroidogenesis in the songbird brain. PMID- 20359329 TI - Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17beta-HSD type 4. AB - BACKGROUND: Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2) is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4), an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ) and females (ZW) because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. RESULTS: Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. CONCLUSIONS: Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z linked gene may occur via post-transcriptional mechanisms. PMID- 20359330 TI - SSHscreen and SSHdb, generic software for microarray based gene discovery: application to the stress response in cowpea. AB - BACKGROUND: Suppression subtractive hybridization is a popular technique for gene discovery from non-model organisms without an annotated genome sequence, such as cowpea (Vigna unguiculata (L.) Walp). We aimed to use this method to enrich for genes expressed during drought stress in a drought tolerant cowpea line. However, current methods were inefficient in screening libraries and management of the sequence data, and thus there was a need to develop software tools to facilitate the process. RESULTS: Forward and reverse cDNA libraries enriched for cowpea drought response genes were screened on microarrays, and the R software package SSHscreen 2.0.1 was developed (i) to normalize the data effectively using spike in control spot normalization, and (ii) to select clones for sequencing based on the calculation of enrichment ratios with associated statistics. Enrichment ratio 3 values for each clone showed that 62% of the forward library and 34% of the reverse library clones were significantly differentially expressed by drought stress (adjusted p value < 0.05). Enrichment ratio 2 calculations showed that > 88% of the clones in both libraries were derived from rare transcripts in the original tester samples, thus supporting the notion that suppression subtractive hybridization enriches for rare transcripts. A set of 118 clones were chosen for sequencing, and drought-induced cowpea genes were identified, the most interesting encoding a late embryogenesis abundant Lea5 protein, a glutathione S transferase, a thaumatin, a universal stress protein, and a wound induced protein. A lipid transfer protein and several components of photosynthesis were down-regulated by the drought stress. Reverse transcriptase quantitative PCR confirmed the enrichment ratio values for the selected cowpea genes. SSHdb, a web accessible database, was developed to manage the clone sequences and combine the SSHscreen data with sequence annotations derived from BLAST and Blast2GO. The self-BLAST function within SSHdb grouped redundant clones together and illustrated that the SSHscreen plots are a useful tool for choosing anonymous clones for sequencing, since redundant clones cluster together on the enrichment ratio plots. CONCLUSIONS: We developed the SSHscreen-SSHdb software pipeline, which greatly facilitates gene discovery using suppression subtractive hybridization by improving the selection of clones for sequencing after screening the library on a small number of microarrays. Annotation of the sequence information and collaboration was further enhanced through a web-based SSHdb database, and we illustrated this through identification of drought responsive genes from cowpea, which can now be investigated in gene function studies. SSH is a popular and powerful gene discovery tool, and therefore this pipeline will have application for gene discovery in any biological system, particularly non-model organisms. SSHscreen 2.0.1 and a link to SSHdb are available from http://microarray.up.ac.za/SSHscreen. PMID- 20359331 TI - The zebra finch neuropeptidome: prediction, detection and expression. AB - BACKGROUND: Among songbirds, the zebra finch (Taeniopygia guttata) is an excellent model system for investigating the neural mechanisms underlying complex behaviours such as vocal communication, learning and social interactions. Neuropeptides and peptide hormones are cell-to-cell signalling molecules known to mediate similar behaviours in other animals. However, in the zebra finch, this information is limited. With the newly-released zebra finch genome as a foundation, we combined bioinformatics, mass-spectrometry (MS)-enabled peptidomics and molecular techniques to identify the complete suite of neuropeptide prohormones and final peptide products and their distributions. RESULTS: Complementary bioinformatic resources were integrated to survey the zebra finch genome, identifying 70 putative prohormones. Ninety peptides derived from 24 predicted prohormones were characterized using several MS platforms; tandem MS confirmed a majority of the sequences. Most of the peptides described here were not known in the zebra finch or other avian species, although homologous prohormones exist in the chicken genome. Among the zebra finch peptides discovered were several unique vasoactive intestinal and adenylate cyclase activating polypeptide 1 peptides created by cleavage at sites previously unreported in mammalian prohormones. MS-based profiling of brain areas required for singing detected 13 peptides within one brain nucleus, HVC; in situ hybridization detected 13 of the 15 prohormone genes examined within at least one major song control nucleus. Expression mapping also identified prohormone messenger RNAs in areas associated with spatial learning and social behaviours. Based on the whole-genome analysis, 40 prohormone probes were found on a commonly used zebra finch brain microarray. Analysis of these newly annotated transcripts revealed that six prohormone probes showed altered expression after birds heard song playbacks in a paradigm of song recognition learning; we partially verify this result experimentally. CONCLUSIONS: The zebra finch peptidome and prohormone complement is now characterized. Based on previous microarray results on zebra finch vocal learning and synaptic plasticity, a number of these prohormones show significant changes during learning. Interestingly, most mammalian prohormones have counterparts in the zebra finch, demonstrating that this songbird uses similar biochemical pathways for neurotransmission and hormonal regulation. These findings enhance investigation into neuropeptide-mediated mechanisms of brain function, learning and behaviour in this model. PMID- 20359333 TI - A graphical vector autoregressive modelling approach to the analysis of electronic diary data. AB - BACKGROUND: In recent years, electronic diaries are increasingly used in medical research and practice to investigate patients' processes and fluctuations in symptoms over time. To model dynamic dependence structures and feedback mechanisms between symptom-relevant variables, a multivariate time series method has to be applied. METHODS: We propose to analyse the temporal interrelationships among the variables by a structural modelling approach based on graphical vector autoregressive (VAR) models. We give a comprehensive description of the underlying concepts and explain how the dependence structure can be recovered from electronic diary data by a search over suitable constrained (graphical) VAR models. RESULTS: The graphical VAR approach is applied to the electronic diary data of 35 obese patients with and without binge eating disorder (BED). The dynamic relationships for the two subgroups between eating behaviour, depression, anxiety and eating control are visualized in two path diagrams. Results show that the two subgroups of obese patients with and without BED are distinguishable by the temporal patterns which influence their respective eating behaviours. CONCLUSION: The use of the graphical VAR approach for the analysis of electronic diary data leads to a deeper insight into patient's dynamics and dependence structures. An increasing use of this modelling approach could lead to a better understanding of complex psychological and physiological mechanisms in different areas of medical care and research. PMID- 20359332 TI - Gene duplication and fragmentation in the zebra finch major histocompatibility complex. AB - BACKGROUND: Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC) has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC) sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines. RESULTS: The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH) evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes. CONCLUSION: The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving chromosomal fission, gene duplication and translocation in the history of the MHC in birds, and highlight striking differences in MHC structure and organization among avian lineages. PMID- 20359334 TI - Air pollution research: visualization of research activity using density equalizing mapping and scientometric benchmarking procedures. AB - BACKGROUND: Due to constantly rising air pollution levels as well as an increasing awareness of the hazardousness of air pollutants, new laws and rules have recently been passed. Although there has been a large amount of research on this topic, bibliometric data is still to be collected. Thus this study provides a scientometric approach to the material published on this subject so far. METHODS: For this purpose, data retrieved from the "Web of Science" provided by the Thomson Scientific Institute was analyzed and visualized both with density equalizing methods and classic data-processing methods such as tables and charts. RESULTS: For the time span between 1955 and 2006, 26,253 items were listed and related to the topic of air pollution, published by 124 countries in 24 different languages. General citation activity has been constantly increasing since the beginning of the examined period. However, beginning with the year 1991, citation levels have been rising exponentially each year, reaching 39,220 citations in the year 2006. The United States, the UK and Germany were the three most productive countries in the area, with English and German ranked first and second in publishing languages, followed by French. An article published by Dockery, Pope, Xu et al. was both the most cited in total numbers and in average citation rate. J. Schwartz was able to claim the highest total number of citations on his publications, while D.W. Dockery has the highest citation rate per publication. As to the subject areas the items are assigned with, the most item were published in Environmental Sciences, followed by Meteorology & Atmospheric Sciences and Public, Environmental & Occupational Health. Nine out of the ten publishing journals with more than 300 entries dealt with environmental interests and one dealt with epidemiology. CONCLUSIONS: Using the method of density-equalizing mapping and further common data processing procedures, it can be concluded that scientific work concerning air pollution and related topics enjoys unbrokenly growing scientific interest. This can be observed both in publication numbers and in citation activity. PMID- 20359335 TI - Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats. AB - BACKGROUND: Fibrosis can be described as the excess deposition of extracellular matrix (ECM) components, such as collagens and proteoglycans. Fibrosis of the liver, which eventually leads to cirrhosis, is a major global health problem. Being able to measure fibrosis progression may enable timely preventative intervention. The aim of the current study was to investigate the utility of serum procollagen type I N-terminal propeptide (PINP) as a marker of hepatic fibrosis, as distinct from bone formation, during three different periods of fibrosis development following hepatic injury induced by bile duct ligation (BDL) in rats. METHODS: BDL was performed on 30 female Sprague-Dawley rats aged 6 months, and sham operations on 30 controls. Animals were killed after 14, 28, or 35 days. The extent of liver fibrosis was evaluated by quantitative histology after Sirus Red staining. Levels of serum PINP and osteocalcin (a marker solely for osteoblastic bone formation) were determined using ELISA at baseline and post termination. RESULTS: Collagen formation increased by 30% compared to 3% in sham operated animals (P < 0.0001). PINP levels increased significantly in all BDL groups compared with baseline (14 days: baseline 13.9 ng/ml, termination 17.7 ng/ml, P = 0.047; 28 days: baseline 17.9 ng/ml, termination 26.2 ng/ml, P = 0.005; 35 days: baseline 18.0 ng/ml, termination 27.4 ng/ml P = 0.015, an increase of 52%). PINP levels did not change from baseline in the sham-operated rats, indicating that the increased PINP levels were due to hepatic injury. The bone-specific marker, osteocalcin, did not increase in either BDL or sham operated rats. PINP measured in serum correlated to the extent of liver fibrosis as evaluated by quantitative histology (R2 = 0.42, P < 0.001). CONCLUSION: PINP was associated with the development of liver fibrosis, but not bone formation, in mature rats subjected to BDL. Thus, PINP may be useful in studying the pathogenesis of liver fibrosis. However, caution should be applied when interpreting PINP levels in other disease states. PMID- 20359336 TI - A novel soft-tissue in vitro model for bisphosphonate-associated osteonecrosis. AB - BACKGROUND: Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) has been reported in patients receiving intravenous BP, particularly zoledronic acid (ZA). The purpose of this study was to develop an in vitro model representative of the effects BP has on soft tissue secondary to its release from bone. Human gingival fibroblasts and oral epithelial cell lines were exposed to various concentrations (0-10 muM) of ZA using dentine discs (DDs) as a direct carrier of BP, which were exposed for 24 hours to ZA in normal medium (NM), washed in phosphate-buffered saline (PBS) and placed in a new co-culture with the cells. The cells were allowed to proliferate until they grew over the bone discs and then the discs either were left unchelated, or were chelated using 0.001% EDTA or EGTA to release BP from the discs and to observe the cellular effects. Direct effects were determined using direct and fluorescent imaging. Apoptotic effects were determined by vital stain, terminal dUTP nick-end labeling, and annexin V studies. The effect on cell proliferation was determined by mitochondrial tetrazolium salt assay. The level of BP release was determined based on the effect of BP directly on cells, using the DDs or the supernatant fluids resulting from chelation. RESULTS: A dose-response effect was seen on imaging, and effects on apoptosis and cell proliferation were observed with increasing ZA concentrations liberated from the DDs, particularly after calcium cleavage and release of ZA from the DDs with a variety of chelating agents. Apoptotic effects were observed microscopically after chelation at 24 hours. Release of ZA was confirmed by extracting medium from non-chelated and chelated cell culture models with DDs and applying this medium to untreated fresh cell cultures, providing appropriate controls. CONCLUSIONS: The results from this study demonstrate that low concentrations of ZA released from bone can rapidly and directly affect the oral mucosal tissues, initially through the induction of apoptosis and long term through the inhibition of cell proliferation. These findings provide an in vitro model for a soft-tissue mechanistic component in the initiation and/or progression of ONJ. PMID- 20359337 TI - Specificity and functionality of microRNA inhibitors. AB - BACKGROUND: Micro(mi)RNAs regulate gene expression through translational attenuation and messenger (m)RNA degradation, and are associated with differentiation, homeostasis and disease. Natural miRNA target recognition is determined primarily by perfect complementarity in a seed region (nucleotide positions 2 to 7) with additional interactions contributing in a sequence- and target-specific manner. Synthetic miRNA target analogs, which are fully complementary, chemically modified oligonucleotides, have been used successfully to inhibit miRNA function. RESULTS: In this paper, we present a first systematic study to evaluate the effect of mismatches in the target site on synthetic inhibitor activity. Panels of miRNA inhibitors containing two-nucleotide mismatches across the target site were tested against three miRNAs (miR-21, miR 22 and miR-122). The results showed that the function of inhibitors vary as mismatch positions in the inhibitors change. CONCLUSIONS: The data indicate that features important for natural miRNA target recognition (such as seed region complementarity) are also important for inhibitor functionality. In addition, base pairing at a second, more 3' region appears to be equally important in determining the efficacy of synthetic inhibitors. Considering the importance of these inhibitor regions and the expression of closely related miRNA sequences will enable researchers to interpret results more accurately in future experiments. PMID- 20359338 TI - Determination of silver nanoparticle release from antibacterial fabrics into artificial sweat. AB - Silver nanoparticles have been used in numerous commercial products, including textiles, to prevent bacterial growth. Meanwhile, there is increasing concern that exposure to these nanoparticles may cause potential adverse effects on humans as well as the environment. This study determined the quantity of silver released from commercially claimed nanosilver and laboratory-prepared silver coated fabrics into various formulations of artificial sweat, each made according to AATCC, ISO and EN standards. For each fabric sample, the initial amount of silver and the antibacterial properties against the model Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria on each fabric was investigated. The results showed that silver was not detected in some commercial fabrics. Furthermore, antibacterial properties of the fabrics varied, ranging from 0% to greater than 99%. After incubation of the fabrics in artificial sweat, silver was released from the different fabrics to varying extents, ranging from 0 mg/kg to about 322 mg/kg of fabric weight. The quantity of silver released from the different fabrics was likely to be dependent on the amount of silver coating, the fabric quality and the artificial sweat formulations including its pH. This study is the unprecedented report on the release of silver nanoparticles from antibacterial fabrics into artificial sweat. This information might be useful to evaluate the potential human risk associated with the use of textiles containing silver nanoparticles. PMID- 20359339 TI - A subtelomeric non-LTR retrotransposon Hebe in the bdelloid rotifer Adineta vaga is subject to inactivation by deletions but not 5' truncations. AB - BACKGROUND: Rotifers of the class Bdelloidea are microscopic freshwater invertebrates best known for: their capacity for anhydrobiosis; the lack of males and meiosis; and for the ability to capture genes from other non-metazoan species. Although genetic exchange between these animals might take place by non canonical means, the overall lack of meiosis and syngamy should greatly impair the ability of transposable elements (TEs) to spread in bdelloid populations. Previous studies demonstrated that bdelloid chromosome ends, in contrast to gene rich regions, harbour various kinds of TEs, including specialized telomere associated retroelements, as well as DNA TEs and retrovirus-like retrotransposons which are prone to horizontal transmission. Vertically-transmitted retrotransposons have not previously been reported in bdelloids and their identification and studies of the patterns of their distribution and evolution could help in the understanding of the high degree of TE compartmentalization within bdelloid genomes. RESULTS: We identified and characterized a non-long terminal repeat (LTR) retrotransposon residing primarily in subtelomeric regions of the genome in the bdelloid rotifer Adineta vaga. Contrary to the currently prevailing views on the mode of proliferation of non-LTR retrotransposons, which results in frequent formation of 5'-truncated ('dead-on-arrival') copies due to the premature disengagement of the element-encoded reverse transcriptase from its template, this non-LTR element, Hebe, is represented only by non-5'-truncated copies. Most of these copies, however, were subject to internal deletions associated with microhomologies, a hallmark of non-homologous end-joining events. CONCLUSIONS: The non-LTR retrotransposon Hebe from the bdelloid rotifer A. vaga was found to undergo frequent microhomology-associated deletions, rather than 5' terminal truncations characteristic of this class of retrotransposons, and to exhibit preference for telomeric localization. These findings represent the first example of a vertically transmitted putatively deleterious TE in bdelloids, and may indicate the involvement of microhomology-mediated non-homologous end-joining in desiccation-induced double-strand break repair at the genome periphery. PMID- 20359340 TI - Creation of a novel telomere-cutting endonuclease based on the EN domain of telomere-specific non-long terminal repeat retrotransposon, TRAS1. AB - BACKGROUND: The ends of chromosomes, termed telomeres consist of repetitive DNA. The telomeric sequences shorten with cell division and, when telomeres are critically abbreviated, cells stop proliferating. However, in cancer cells, by the expression of telomerase which elongates telomeres, the cells can continue proliferating. Many approaches for telomere shortening have been pursued in the past, but to our knowledge, cutting telomeres in vivo has not so far been demonstrated. In addition, there is lack of information on the cellular effects of telomere shortening in human cells. RESULTS: Here, we created novel chimeric endonucleases to cut telomeres by fusing the endonuclease domain (TRAS1EN) of the silkworm's telomere specific non-long terminal repeat retrotransposon TRAS1 to the human telomere-binding protein, TRF1. An in vitro assay demonstrated that the TRAS1EN-TRF1 chimeric endonucleases (T-EN and EN-T) cut the human (TTAGGG)n repeats specifically. The concentration of TRAS1EN-TRF1 chimeric endonucleases necessary for the cleavage of (TTAGGG)n repeats was about 40-fold lower than that of TRAS1EN alone. When TRAS1EN-TRF1 endonucleases were introduced into human U2OS cancer cells using adenovirus vectors, the enzymes localized at telomeres of nuclei, cleaved and shortened the telomeric DNA by double-strand breaks. When human U2OS and HFL-1 fibroblast cells were infected with EN-T recombinant adenovirus, their cellular proliferation was suppressed for about 2 weeks after infection. In contrast, the TRAS1EN mutant (H258A) chimeric endonuclease fused with TRF1 (ENmut-T) did not show the suppression effect. The EN-T recombinant adenovirus induced telomere shortening in U2OS cells, activated the p53-dependent pathway and caused the senescence associated cellular responses, while the ENmut T construct did not show such effects. CONCLUSIONS: A novel TRAS1EN-TRF1 chimeric endonuclease (EN-T) cuts the human telomeric repeats (TTAGGG)n specifically in vitro and in vivo. Thus, the chimeric endonuclease which is expressed from an adenoviral vector can suppress cell proliferation of cancer cells. PMID- 20359341 TI - Effectiveness of community based Safe Motherhood promoters in improving the utilization of obstetric care. The case of Mtwara Rural District in Tanzania. AB - BACKGROUND: In Tanzania, maternal mortality ratio remains unacceptably high at 578/100,000 live births. Despite a high coverage of antenatal care (96%), only 44% of deliveries take place within the formal health services. Still, "Ensure skilled attendant at birth" is acknowledged as one of the most effective interventions to reduce maternal deaths. Exploring the potential of community based interventions in increasing the utilization of obstetric care, the study aimed at developing, testing and assessing a community-based safe motherhood intervention in Mtwara rural District of Tanzania. METHOD: This community-based intervention was designed as a pre-post comparison study, covering 4 villages with a total population of 8300. Intervention activities were implemented by 50 trained safe motherhood promoters (SMPs). Their tasks focused on promoting early and complete antenatal care visits and delivery with a skilled attendant. Data on all 512 deliveries taking place from October 2004 to November 2006 were collected by the SMPs and cross-checked with health service records. In addition 242 respondents were interviewed with respect to knowledge on safe motherhood issues and their perception of the SMP's performance. Skilled delivery attendance was our primary outcome; secondary outcomes included antenatal care attendance and knowledge on Safe Motherhood issues. RESULTS: Deliveries with skilled attendant significantly increased from 34.1% to 51.4% (rho < 0.05). Early ANC booking (4 to 16 weeks) rose significantly from 18.7% at baseline to 37.7% in 2005 and 56.9% (rho < 0.001) at final assessment. After two years 44 (88%) of the SMPs were still active, 79% of pregnant women were visited. Further benefits included the enhancement of male involvement in safe motherhood issues. CONCLUSION: The study has demonstrated the effectiveness of community-based safe motherhood intervention in promoting the utilization of obstetric care and a skilled attendant at delivery. This improvement is attributed to the SMPs' home visits and the close collaboration with existing community structures as well as health services. PMID- 20359342 TI - Quantifying culture gaps between physicians and managers in Dutch hospitals: a survey. AB - BACKGROUND: The demands in hospitals for safety and quality, combined with limitations in financing health care require effective cooperation between physicians and managers. The complex relationship between both groups has been described in literature. We aim to add a perspective to literature, by developing a questionnaire which provides an opportunity to quantitatively report and elaborate on the size and content of differences between physicians and managers. Insight gained from use of the questionnaire might enable us to reflect on these differences and could provide practical tools to improve cooperation between physicians and managers, with an aim to enhance hospital performance. METHODS: The CG-Questionnaire was developed by adjusting, pre-testing, and shortening Kralewski's questionnaire, and appeared suitable to measure culture gaps. It was shortened by exploratory factor analysis, using principal-axis factoring extraction with Varimax rotation. The CG-Questionnaire was sent to all physicians and managers within 37 Dutch general hospitals. ANOVA and paired sample T-tests were used to determine significant differences between perceptions of daily work practices based in both professional cultures; culture gaps. The size and content of culture gaps were determined with descriptive statistics. RESULTS: The total response (27%) consisted of 929 physicians and 310 managers. The Cronbachs alpha's were 0.70 - 0.79. Statistical analyses showed many differences; culture gaps were found in the present situation; they were even larger in the preferred situation. Differences between both groups can be classified into three categories: (1) culture gaps in the present situation and not in the preferred, (2) culture gaps in the preferred situation and not in the present, and (3) culture gaps in both situations. CONCLUSIONS: With data from the CG-Questionnaire it is now possible to measure the size and content of culture gaps between physicians and managers in hospitals. Results gained with the CG-Questionnaire enables hospitals to reflect on these differences. Combining the results, we distinguished three categories of increasing complexity. We linked these three categories to three methods from intergroup literature (enhanced information, contact and ultimately meta cognition) which could help to improve the cooperation between physicians and managers. PMID- 20359343 TI - Uncommon cause for anterior knee pain - Aggressive aneurysmal bone cyst of the patella. AB - A 56-year-old man presented with a two month history of increasing anterior knee pain without previous trauma. As usual we recommended physiotherapy with stretching exercises of the quadriceps muscle. Since symptoms did not improve after 6 weeks MRI was performed. Surprisingly a hyperintense lobulated mass of the patella with small fluid-filled cavities at the inferior pole was revealed. We performed an open biopsy to exclude any malignancy and diagnosed an aneurysmal bone cyst. Further examination with CT scans showed an aggressive behaviour with cortical breakthrough.We performed an intralesional curettage with additional high-speed burring and bone cement packing. Sixteen months later the patient was free from any complaints and without signs of local recurrence.Primary bone tumors of the patella are extremely rare and occurrence of aneurysmal bone cysts in this localization is very uncommon. This case report indicates that although anterior knee pain is a very frequent and usually harmless symptom, it is essential to consider that it might also be caused by more severe disorders such as bone tumors. PMID- 20359344 TI - Evaluation of a novel approach for the measurement of RNA quality. AB - BACKGROUND: Microarray data interpretation can be affected by sample RNA integrity. The ScreenTape Degradation Value (SDV) is a novel RNA integrity metric specific to the ScreenTape(R) platform (Lab901). To characterise the performance of the ScreenTape(R) platform for RNA analysis and determine the robustness of the SDV metric, a panel of intentionally degraded RNA samples was prepared. These samples were used to evaluate the ScreenTape(R) platform against an alternative approach for measuring RNA integrity (Agilent Bioanalyzer RIN value). The samples were also subjected to microarray analysis and the resulting data correlated to the RNA integrity metrics. FINDINGS: Measurement of SDV for a panel of intentionally degraded RNA samples ranged from 0 for intact RNA to 37 for degraded RNA, with corresponding RIN values ranging from 10 to 4 for the same set of samples. SDV and RIN scales both demonstrated comparable discrimination between differently treated samples (RIN 10 to 7, SDV 0 to 15), with the SDV exhibiting better discrimination at higher degradation levels. Increasing SDV values correlated with a decrease in microarray sample labelling efficiency and an increase in numbers of differentially expressed genes. CONCLUSIONS: The ScreenTape(R) platform is comparable to the Bioanalyzer platform in terms of reproducibility and discrimination between different levels of RNA degradation. The robust nature of the SDV metric qualifies it as an alternative metric for RNA sample quality control, and a useful predictor of downstream microarray performance. PMID- 20359345 TI - Surviving within the amoebal exocyst: the Mycobacterium avium complex paradigm. AB - BACKGROUND: Most of environmental mycobacteria have been previously demonstrated to resist free-living amoeba with subsequent increased virulence and resistance to antibiotics and biocides. The Mycobacterium avium complex (MAC) comprises of environmental organisms that inhabit a wide variety of ecological niches and exhibit a significant degree of genetic variability. We herein studied the intra ameobal location of all members of the MAC as model organisms for environmental mycobacteria. RESULTS: Type strains for M. avium, Mycobacterium intracellulare, Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense, Mycobacterium marseillense, Mycobacterium timonense and Mycobacterium bouchedurhonense were co-cultivated with the free-living amoeba Acanthamoeba polyphaga strain Linc-AP1. Microscopic analyses demonstrated the engulfment and replication of mycobacteria into vacuoles of A. polyphaga trophozoites. Mycobacteria were further entrapped within amoebal cysts, and survived encystment as demonstrated by subculturing. Electron microscopy observations show that, three days after entrapment into A. polyphaga cysts, all MAC members typically resided within the exocyst. CONCLUSIONS: Combined with published data, these observations indicate that mycobacteria are unique among amoeba-resistant bacteria, in residing within the exocyst. PMID- 20359346 TI - A preliminary survey of the practice patterns of United States Guild Certified Feldenkrais PractitionersCM. AB - BACKGROUND: The Feldenkrais Method(R) of somatic education purports to guide people of varying ages and abilities to improve function. Many people choose this method to aid with recovery from injury, manage chronic conditions, or enhance performance even though limited research supporting its safety and effectiveness exists to guide decisions about use and referral. Very little information about practitioner characteristics and practice patterns is publicly available to assist researchers in the design of appropriate safety and effectiveness studies. The purpose of this study was to obtain an initial overview of the characteristics of United States Guild Certified Feldenkrais PractitionersCM. METHODS: Of 1300 certified Feldenkrais practitioners at the time of the study, there were 1193 practitioners with email accounts who were sent invitations to complete a web-based survey. The survey inquired about practice locations, additional credentials, service patterns and workloads during the previous 3 months. Response rate and descriptive statistics were calculated. RESULTS: The survey had a 32.3% (385/1193) response rate. The top states in which responders practiced were California (n = 92) and New York (n = 44). Most responders did not hold other credentials as traditional health care providers or as complementary and alternative medicine providers. Among those who did, the most common credentials were physical therapist (n = 83) and massage therapist (n = 38). Just over a third of traditional health care providers only provided Feldenkrais lessons, compared to 59.3% of complementary and alternative providers. On average, responders saw 7.6 +/- 8.1 (median = 5) clients per week for individual lessons, 8.4 +/- 11.5 (median = 5) clients per week for group lessons, and 2.9 +/ 3.9 (median = 2) new clients per month for individual lessons. CONCLUSIONS: This preliminary survey of United States Guild Certified Feldenkrais Practitioners indicated that most practiced in the west and northeast, did not hold additional credentials, and had part-time practices. Those who were traditional health care providers were more likely than complementary and alternative medicine providers in other areas to combine their services. These results provide a foundation for further analyses of Feldenkrais practitioner characteristics and practice patterns that can aid the design of safety and effectiveness studies, and enhance use and referral decision-making. PMID- 20359347 TI - The Trichoderma harzianum demon: complex speciation history resulting in coexistence of hypothetical biological species, recent agamospecies and numerous relict lineages. AB - BACKGROUND: The mitosporic fungus Trichoderma harzianum (Hypocrea, Ascomycota, Hypocreales, Hypocreaceae) is an ubiquitous species in the environment with some strains commercially exploited for the biological control of plant pathogenic fungi. Although T. harzianum is asexual (or anamorphic), its sexual stage (or teleomorph) has been described as Hypocrea lixii. Since recombination would be an important issue for the efficacy of an agent of the biological control in the field, we investigated the phylogenetic structure of the species. RESULTS: Using DNA sequence data from three unlinked loci for each of 93 strains collected worldwide, we detected a complex speciation process revealing overlapping reproductively isolated biological species, recent agamospecies and numerous relict lineages with unresolved phylogenetic positions. Genealogical concordance and recombination analyses confirm the existence of two genetically isolated agamospecies including T. harzianum sensu stricto and two hypothetical holomorphic species related to but different from H. lixii. The exact phylogenetic position of the majority of strains was not resolved and therefore attributed to a diverse network of recombining strains conventionally called 'pseudoharzianum matrix'. Since H. lixii and T. harzianum are evidently genetically isolated, the anamorph - teleomorph combination comprising H. lixii/T. harzianum in one holomorph must be rejected in favor of two separate species. CONCLUSIONS: Our data illustrate a complex speciation within H. lixii - T. harzianum species group, which is based on coexistence and interaction of organisms with different evolutionary histories and on the absence of strict genetic borders between them. PMID- 20359348 TI - Bax inhibitor-1 down-regulation in the progression of chronic liver diseases. AB - BACKGROUND: Bax inhibitor-1 (BI-1) is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1) to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2) to determine whether HCV and HBV infections modulate said expression. METHODS: We examined 62 patients: 39 with chronic hepatitis (CH) (31 HCV-related and 8 HBV-related); 7 with cirrhosis (6 HCV-related and 1 HBV-related); 13 with hepatocellular carcinoma (HCC) [7 in viral cirrhosis (6 HCV- and 1 HBV-related), 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. RESULTS: CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P < 0.0001) or HCC (P < 0.0001). Significantly higher Bax transcripts were observed in HCV-genotype-1-related than in HCV-genotype-3-related CH (P = 0.033). A positive correlation emerged between BI-1 and Bax transcripts in CH tissues, even when HCV-related CH and HCV-genotype-1-related CH were considered alone (P = 0.0007, P = 0.0005 and P = 0.0017, respectively). CONCLUSIONS: BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression. PMID- 20359349 TI - Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology. AB - BACKGROUND: The availability of clinically valid biomarkers contribute to improve the diagnosis and clinical management of diseases. A valine-to-phenylalanine substitution at position 617 (V617F) in the Janus kinase 2 (JAK2) gene has been recently associated with key signaling abnormalities in the transduction of haemopoietic growth-factor receptors and is now considered as a useful clinical marker of myeloproliferative neoplasms. Several methods have recently been reported to detect the JAK2 V617F point mutation and show variable sensitivity. METHODS: Using the Luminex xMAP technology, we developed a quantitative assay to detect the JAK2V617F variant. The method was based on polymerase chain reaction (PCR) followed by hybridization to specific probes coupled with internally dyed microspheres. The assay comprises 3 steps: genomic DNA extraction, end point PCR reaction, direct hybridization of PCR fragments and quantification. It has been tested with different sources of nucleic acid. RESULTS: Applied to whole blood samples, this quantitative assay showed a limit of detection of 2%. A highly sensitive allele-specific primer extension reaction performed in parallel allowed to validate the results and to identify the specimens with values below 2%. CONCLUSION: Direct hybridization assay using the Luminex xMAP technology allows sensitive quantification of JAK2V617F from blood spots. It is simple and can be easily performed in a clinical setting. PMID- 20359350 TI - Establishment and identification of a rabbit model of peritoneal carcinomatosis from gastric cancer. AB - BACKGROUND: Gastric cancer peritoneal carcinomatosis is a common clinical problem, but there are no suitable large animal models to study this problem. This study was to establish a stable rabbit peritoneal carcinomatosis model of gastric cancer using VX2 tumor, and analyze the clinico-pathological features. METHODS: VX2 tumor was implanted into 36 New Zealand rabbits by 3 methods: laparotomic orthotopic injection of cancer cells into the submucosal layer of the stomach (Group A), laparotomic implantation of tumor tissue into the greater omentum immediately beneath the gastric antrum (Group B), and percutaneous injection of tumor cells directly into the peritoneal cavity (Group C), 12 rabbits in each group. The animals were closely observed and detailed clinico pathological studies were conducted. RESULTS: The success rates of peritoneal carcinomatosis formation were 100% (12/12), 91.7% (11/12) and 58.3% (7/12), respectively, for Groups A, B and C (P = 0.019, A versus C; P = 0.077, B versus C; P = 0.500, A versus B, Fisher's exact test). Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous pulmonary metastases. The clinico-pathological progression pattern was very similar to patients of advanced gastric cancer with peritoneal carcinomatosis. Groups B and C showed similar pattern of cancer progression, but less aggressive. CONCLUSIONS: First large animal model of peritoneal carcinomatosis from gastric cancer has been established by laparotomic orthotopic injection of VX2 cancer cells into the submucosal layer of the stomach, providing a more suitable model for surgical interventional studies. The clinico-pathological features of this model resemble human peritoneal carcinomatosis. PMID- 20359351 TI - New symmetry of intended curved reaches. AB - BACKGROUND: Movement regularities are inherently present in automated goal directed motions of the primate's arm system. They can provide important signatures of intentional behaviours driven by sensory-motor strategies, but it remains unknown if during motor learning new regularities can be uncovered despite high variability in the temporal dynamics of the hand motions. METHODS: We investigated the conservation and violation of new movement regularity obtained from the hand motions traced by two untrained monkeys as they learned to reach outwardly towards spatial targets while avoiding obstacles in the dark. The regularity pertains to the transformation from postural to hand paths that aim at visual goals. RESULTS: In length-minimizing curves the area enclosed between the Euclidean straight line and the curve up to its point of maximum curvature is 1/2 of the total area. Similar trend is found if one examines the perimeter. This new movement regularity remained robust to striking changes in arm dynamics that gave rise to changes in the speed of the reach, to changes in the hand path curvature, and to changes in the arm's postural paths. The area and perimeter ratios characterizing the regularity co-varied across repeats of randomly presented targets whenever the transformation from posture to hand paths was compliant with the intended goals. To interpret this conservation and the cases in which the regularity was violated and recovered, we provide a geometric model that characterizes arm-to-hand and hand-to-arm motion paths as length minimizing curves (geodesics) in a non-Euclidean space. Whenever the transformation from one space to the other is distance-metric preserving (isometric) the two symmetric ratios co-vary. Otherwise, the symmetric ratios and their co-variation are violated. As predicted by the model we found empirical evidence for the violation of this movement regularity whenever the intended goals mismatched the actions. This was manifested in unintended curved "after-effect" trajectories executed in the absence of obstacles. In this case, the system was "perturbed" away from the symmetry but after several repeats it recovered its default state. CONCLUSIONS: We propose this movement regularity as a sensory-motor transformation invariant of intentional acts. PMID- 20359352 TI - Prospective monitoring of cefepime in intensive care unit adult patients. AB - INTRODUCTION: Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia. METHODS: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis. RESULTS: Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest. CONCLUSIONS: These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs 813 ml/d, n 390). Heavy drinkers had a decreased risk (RR = 0.28, 95 % CI 0.08, 0.98) for depression when compared with non-drinkers, after adjustment for age and examination years. Further adjustment for socio-economic status, alcohol consumption, smoking, maximal oxygen uptake, BMI and the energy-adjusted daily intakes of folate and PUFA did not attenuate this association (relative risk (RR) = 0.23, 95 % CI 0.06, 0.83). No associations were observed between depression and intake of tea (drinkers v. non-drinkers; RR = 1.19, 95 % CI 0.54, 2.23) or caffeine (highest quartile v. lowest quartile; RR = 0.99, 95 % CI 0.40, 2.45). CONCLUSIONS: Coffee consumption may decrease the risk of depression, whereas no association was found for tea and caffeine intake. PMID- 20359378 TI - Actual use of a front-of-pack nutrition logo in the supermarket: consumers' motives in food choice. AB - OBJECTIVE: A front-of-pack nutrition logo on products with relatively favourable product compositions might help consumers to make more healthful choices. Studies investigating actual nutrition label use in point-of-purchase settings are scarce. The present study investigates the use of the 'Choices' nutrition logo in Dutch supermarkets. DESIGN: Adults were asked to complete a validated questionnaire about motivation for food choice and their purchased products were scored for the Choices logo after they had done their shopping. SETTING: Nine supermarkets in The Netherlands. SUBJECTS: A total of 404 respondents participated. RESULTS: Of the respondents, 62 % reported familiarity with the logo. The motivations for food choice that were positively associated with actually purchasing products with the logo were attention to 'weight control' and 'product information'. The food choice motive 'hedonism' was negatively associated with purchasing products with the logo. CONCLUSIONS: This is the first study to investigate actual use of the Choices logo. In order to stimulate consumers to purchase more products with a favourable product composition, extra attention should be paid to hedonistic aspects such as the tastefulness and the image of healthy products. PMID- 20359379 TI - Quality, but not cost, of diet is associated with 5-year incidence of CVD: the ATTICA study. AB - OBJECTIVE: The aim of the present work was to calculate the current cost of the Mediterranean diet in Greece and to evaluate the role of diet cost in the development of cardiovascular events after a 5-year follow-up. DESIGN: Cross sectional. Cost of diet was measured in ?/week based on common Greek dietary choices, while baseline dietary habits were assessed through a semi-quantitative FFQ (Greek-EPIC). The Mediterranean Diet Score (MedDietScore) was applied to assess overall adherence to this pattern using scores of eleven food variables and alcohol, according to the principles of the Mediterranean diet. SETTING: Five year follow-up of the ATTICA study, a nutrition and health survey of a representative, free-living sample of the Greek population resident in the province of Attica, where Athens is a major metropolis. SUBJECTS: From 2001 to 2002, 1514 men and 1528 women (aged >18 years) without known CVD were enrolled. In 2006, the 5-year follow-up was performed. RESULTS: The weekly cost of participants' diets varied from 5.35 to 83.57 ?/week in men (mean 25.45 (sd 6.80) ?/week) and from 10.89 to 55.49 ?/week in women (mean 25.63 (sd 6.30) ?/week). Diet cost was correlated marginally to MedDietScore (r = 0.060, P = 0.05) as well as being associated with history of hypercholesterolaemia (mean (sd), yes v. no: 24.90 (5.73) v. 25.82 (6.95) ?/week, P = 0.027), physical activity (mean (sd), yes v. no: 26.42 (6.90) v. 24.82 (6.20) ?/week, P < 0.001) and current smoking (mean (sd), yes v. no: 24.99 (6.40) v. 25.98 (6.70) ?/week, P = 0.017). No significant association was found between diet cost and 5-year incidence of CVD (hazard ratio = 1.021, 95 % CI 0.965, 1.081). However, adherence to the traditional Mediterranean diet was inversely associated with the development of CVD (relative risk per 1-unit increase in MedDietScore = 0.92, 95 % CI 0.89, 0.94) after adjustment for various potential confounders including diet cost. CONCLUSIONS: Quality but not cost of the diet is associated with the development of CVD. PMID- 20359380 TI - Endemic goitre and excessive iodine in urine and drinking water among Saharawi refugee children. AB - OBJECTIVE: To assess the prevalence of enlarged thyroid volume (Tvol) in Saharawi refugee children, and their urinary iodine concentration (UIC), and to identify possible sources of excess iodine intake. DESIGN: A cross-sectional survey was performed during January-February 2007. Tvol was measured by ultrasound and iodine concentration was analysed in casual urine samples, in household drinking water and in milk samples from household livestock. SETTING: The study was undertaken in four refugee camps in the Algerian desert. SUBJECTS: The subjects were 421 Saharawi children, 6-14 years old. RESULTS: Enlarged Tvol was found in 56 % (Tvol-for-age) and 86 % (Tvol-for-body-surface-area) of the children. The median (25th percentile-75th percentile, P25-P75) UIC was 565 (357-887) microg/l. The median (P25-P75) iodine concentration in household drinking water was 108 (77 297) microg/l. None of the children had UIC below 100 microg/l, 16 % had UIC between 100 and 299 microg/l, and 84 % had UIC above 300 microg/l. There was a positive association between Tvol and whether the household possessed livestock. CONCLUSIONS: The children are suffering from endemic goitre and high UIC caused probably by an excessive intake of iodine. The excessive iodine intakes probably originate from drinking water and milk. PMID- 20359381 TI - Three-dimensional training. PMID- 20359382 TI - What we mean by community orientation - and how do we teach it? PMID- 20359383 TI - The PMETB National Trainee Survey: is it a useful tool? PMID- 20359384 TI - Continuing professional development for general practitioners in the first five years after training. PMID- 20359385 TI - Consensus paper: resources for teaching critical appraisal. PMID- 20359386 TI - Closing the gap between expectations and practice in continuity of care: can we still teach continuity of care? AB - An educational improvement audit of general practitioner (GP) training in continuity of patient care with special reference to patients with long-term conditions was commissioned by a postgraduate medical and dental deanery. The audit comprised interviews (n = 13) with GP trainers, trainees and GPs who had recently completed their training. These interviews were thematically analysed and the findings discussed in workshops with stakeholders in GP education. The interviews showed that trainers and trainees found considerable difficulty in reconciling the values of continuity of care with recent changes in policy and practice. It was also found that while training practices could demonstrate aspects of continuity of patient care, it was difficult to give trainees practical experience and responsibilities that could underline and reinforce this. Newly qualified GPs found it particularly difficult to maintain and apply their understanding of continuity of care in the realities of practice after moving on from their training practice and before obtaining a long-term GP post. The workshops formulated proposals for a series of measures to make continuity of care, in all its forms, more explicit in every element of training and in support for professional development. These proposals were analysed to develop a phased action programme and to assess their cost and utility. This showed great potential to improve the value of training in continuity of care for GP practices and trainees, and ultimately for patients. PMID- 20359387 TI - Moving general practitioner training into primary care with cluster-based learning: a qualitative study in the West Midlands. AB - This study sought to explore the early implementation of cluster-based learning (CBL) pilots in one part of the UK. A qualitative study using semi-structured one to-one interviews was conducted with 10 key informants responsible for managing and delivering local training programmes across 14 general practice specialty training schemes. Data were analysed using thematic content analysis using the constant comparative method. Wide variation existed in the running of CBL pilots between different schemes. The principal reasons for trialling CBL were the high numbers of general practitioner trainees, resulting in extra pressure placed on postgraduate education facilities. Training programme directors (TPDs) managed and facilitated the current pilots. Effective facilitation of the groups was considered essential, along with good organisation and planning, and enthusiastic facilitators. Having a mixture of specialist trainees from different stages of training promoted shared learning in the group. The cluster-based approach was also judged to enable the targeting of training to meet the needs of learners and to address specific local needs. Responders considered that CBL should ultimately comprise learner-led sessions facilitated by educational supervisors, with TPDs being responsible for leading the improvement of the quality of educational and clinical supervision. The main reasons why CBL was not implemented were anxieties about the risks of losing the perceived benefits of the current training format in the absence of evidence of the added value of CBL. The reluctance of trainers to get involved was a major barrier - this resulted mainly from a lack of confidence with facilitating small groups and funding for their time. PMID- 20359388 TI - Some effects of teaching undergraduate medical students on general practitioner thinking and learning. AB - BACKGROUND: This study examined the processes of thinking and learning undertaken by general practitioners (GPs, family physicians) brought about by the presence of undergraduate medical students. METHOD: A qualitative study was undertaken using critical incident templates (a novel approach in this context) and focus groups. Data were analysed thematically, with iterative discussion between members of the study team after independent analysis. RESULTS: Thirty-eight critical incident templates were returned (40%), of which 27 (28%) were completed. Three themes were identified: challenges to the GP's thinking or learning behaviour (these included having to justify actions and answer questions); changes to the dynamic between doctor and patient (listening to discussion of their condition between doctor and student was reported to change the patient's experience); and additions to the GP's workload. Teaching made GPs' day longer and sometimes caused friction with colleagues. CONCLUSIONS: Our data elucidate a range of thinking and learning activities that are brought about by the presence of a student in a GP's consulting room. They show that there are a number of challenges that stimulate these activities. We recommend that undergraduate teaching in general practice be given greater recognition for the stimulus it provides for continuing professional development. PMID- 20359389 TI - Why do general practitioners apply to do an MSc in primary healthcare? A retrospective study. AB - The aim of this study was to examine the characteristics of general practitioners (GPs) applying to the MSc in Primary Health Care at King's College London and their reasons for doing so, and to see whether these have changed during the last 20 years. Demographic data came from 157 applications submitted between 1986 and 2006. GPs' answers to an open-ended question on the reasons for applying were analysed, using both qualitative and quantitative methods. Male sex (66%) and experience of 11.1 (+/-7.1) years in primary care characterised the GPs. Six reasons for applying were identified: (a) career development; (b) personal development; (c) understanding the context of general practice; (d) to improve job satisfaction; (e) to improve clinical practice; and (f) to be a member of an educational group. Understanding the context of general practice was stated more frequently by GPs in the later cohorts (P < 0.05), who also tended to have had less experience of general practice (8.3 versus 11.1 years, P < 0.05). Understanding the developing discipline of general practice is an increasingly important motivation in applying for an MSc, and one that is identified earlier in GPs' careers. The requirement of appraisals and the advent of revalidation may motivate many more GPs to pursue Master's study. Postgraduate educators need to continue to ensure that their programmes reflect the changing landscape of primary care. PMID- 20359390 TI - The FORMATIVE approach to enhanced appraisal. PMID- 20359391 TI - The educational benefits of a federation of four training practices. PMID- 20359392 TI - Practical ideas on how to teach community orientation. PMID- 20359393 TI - How to ... Carry out a literature search. PMID- 20359394 TI - The management and quality of GP specialty training in the light of the requirements set out by the Postgraduate Medical Education and Training Board. PMID- 20359395 TI - Promoting unprofessionalism in the UAE? PMID- 20359396 TI - Usability: a critical dimension for assessing the quality of clinical systems. PMID- 20359397 TI - When your words count: a discriminative model to predict approval of referrals. AB - OBJECTIVE: To develop and test a statistical model which correctly predicts the approval of outpatient referrals when reviewed by a specialty service based on nine discriminating variables. DESIGN: Retrospective cross-sectional study. SETTING: Large public county hospital system in a southern US city. PARTICIPANTS: Written documents and associated data from 500 random adult referrals made by primary care providers to various specialty services during the course of one month. MAIN OUTCOME MEASURES: The resulting correct prediction rates obtained by the model. RESULTS: The model correctly predicted 78.6% of approved referrals using all nine discriminating variables, 75.3% of approved referrals using all variables in a stepwise manner and 74.7% of approved referrals using only the referral total word count as a single discriminating variable. CONCLUSIONS: Three iterations of the model correctly predicted at least 75% of the approved referrals in the validation set. A correct prediction of whether or not a referral will be approved can be made in three out of four cases. PMID- 20359398 TI - Electronic patient record evaluation in community mental health. AB - BACKGROUND: Deployment of electronic patient records (EPRs) is one of the primary goals of national NHS information technology (IT) initiatives. However, many systems come into disrepute through poor planning or design flaws, and media scrutiny focuses on these problems rather than the potential gains. OBJECTIVE: To evaluate the deployment of an EPR in a community mental health setting. METHOD: A validated user questionnaire was issued to all clinically qualified staff working in community mental health teams followed by interview and validation phases. The study encompassed both quantitative and qualitative mechanisms to establish the efficacy and usability of the system. RESULTS: The questionnaire had a response rate of 49.3%. Overall, the response was positive, with almost no extreme negative responses. Of respondents, 88.5% were satisfied with system accuracy, while 91.7% of responses indicated that data was made available in a timely manner. Of those surveyed, 88.7% agreed the system was 'worth the time and effort required to use it'. Additionally, electronic notes are used more frequently than paper-based equivalents. CONCLUSION: The research concludes that the implemented system appears to offer a robust EPR that gives its users a high degree of satisfaction and provides tangible benefits to clinical staff. PMID- 20359399 TI - Identifying the optimal search strategy for coronary heart disease patients in primary care electronic patient record systems. AB - OBJECTIVES: General practitioners are increasingly required to practice in a paperless environment and to collect clinical data electronically on electronic patient record (EPR) systems. A principal step in meeting general practice information needs continues to be the establishment of disease registers and consequently the identification of patient populations within primary care databases is a prerequisite. This study aims to identify and validate the optimal search strategy for coronary heart disease (CHD). METHODS: A multiple logistic regression model for the identification of CHD patients was developed in one site using electronic data, the receiver operating characteristic (ROC) curve and Bayesian statistics. The model was tested on two trial sites. RESULTS: Young male CHD patients are more easily identified by generic searches than older females. The optimal search strategy for CHD was found to be the diagnostic code for CHD, nitrate and digoxin but this was dependent on the disease description, age and sex of the study population and the coding system used within the database. Diagnostic code for CHD identified 80.6% (95% confidence interval (CI) 77-83%), 90.0% (CI 88-92%) and 95.9% (CI 94-97%) of local, national and international definitions respectively, with 100% positive predictive values (PPVs) for all definitions. CONCLUSION: Generic queries may inadvertently perpetuate inequalities in health care. Queries should be bespoke and mindful of the conceptualization of disease by the clinicians recording these data. PMID- 20359401 TI - Documentation-based clinical decision support to improve antibiotic prescribing for acute respiratory infections in primary care: a cluster randomised controlled trial. AB - BACKGROUND AND OBJECTIVE: Clinical guidelines discourage antibiotic prescribing for many acute respiratory infections (ARIs), especially for non-antibiotic appropriate diagnoses. Electronic health record (EHR)-based clinical decision support has the potential to improve antibiotic prescribing for ARIs. METHODS: We randomly assigned 27 primary care clinics to receive an EHR-integrated, documentation-based clinical decision support system for the care of patients with ARIs - the ARI Smart Form - or to offer usual care. The primary outcome was the antibiotic prescribing rate for ARIs in an intent-to-intervene analysis based on administrative diagnoses. RESULTS: During the intervention period, patients made 21 961 ARI visits to study clinics. Intervention clinicians used the ARI Smart Form in 6% of 11 954 ARI visits. The antibiotic prescribing rate in the intervention clinics was 39% versus 43% in the control clinics (odds ratio (OR), 0.8; 95% confidence interval (CI), 0.6-1.2, adjusted for clustering by clinic). For antibiotic appropriate ARI diagnoses, the antibiotic prescribing rate was 54% in the intervention clinics and 59% in the control clinics (OR, 0.8; 95% CI, 0.5 1.3). For non-antibiotic appropriate diagnoses, the antibiotic prescribing rate was 32% in the intervention clinics and 34% in the control clinics (OR, 0.9; 95% CI, 0.6-1.4). When the ARI Smart Form was used, based on diagnoses entered on the form, the antibiotic prescribing rate was 49% overall, 88% for antibiotic appropriate diagnoses and 27% for non-antibiotic appropriate diagnoses. In an as used analysis, the ARI Smart Form was associated with a lower antibiotic prescribing rate for acute bronchitis (OR, 0.5; 95% CI, 0.3-0.8). CONCLUSIONS: The ARI Smart Form neither reduced overall antibiotic prescribing nor significantly improved the appropriateness of antibiotic prescribing for ARIs, but it was not widely used. When used, the ARI Smart Form may improve diagnostic accuracy compared to administrative diagnoses and may reduce antibiotic prescribing for certain diagnoses. PMID- 20359400 TI - Many family physicians will not manually update PDA software: an observational study. AB - BACKGROUND: In a prospective study to explore connections between clinical information delivery and information retrieval, 41 Canadian family physicians searched an electronic knowledge resource (EKR) as needed for practice. Research software, called the Information Assessment Method (IAM), prompted family physicians to report on the situational relevance, perceived cognitive impact and application of their retrieved information hits. Both the IAM and the EKR needed periodic updating to properly address our research questions. OBJECTIVE: To determine the frequency of software updating when manual or semi-automatic approaches are used by family physicians. METHODS: Each family physician received a handheld computer (PDA) that ran the Windows Mobile 6 operating system. For technical reasons, both the IAM and the EKR were accessed offline on PDA. To update the EKR and the IAM, family physicians were asked to synchronize their PDA to their PC. Updating the IAM was a manual process, whereas updating the EKR was semi-automatic. RESULTS: We found: (1) about 25% of family physicians never or rarely updated PDA software on their own, (2) a large number of software updates were never installed and (3) the semi-automatic method was associated with a small increase in the proportion of installed software updates (58.9% versus 48.6% for the manual method). CONCLUSIONS: When a wireless internet connection is not used to update PDA software, sociotechnical issues complicate mobile data collection and data transfer. PMID- 20359402 TI - Physicians' attitudes towards eprescribing: a comparative web survey in Austria and Sweden. AB - BACKGROUND: The eHealth Action Plan required the member states of the European Union (EU) to provide online services such as eprescribing of pharmaceuticals by the end of 2008. So far, implementation activities and efforts of the member states have been uneven. While in Austria pilot projects and feasibility studies have been conducted, Sweden has always been one of the leading countries in the field of eprescribing. OBJECTIVE: To identify potential success factors for the implementation of eprescribing in Sweden, by comparing the attitudes of Austrian and Swedish physicians. METHOD: In a web survey, we asked 1824 Austrian and 427 Swedish physicians within primary care and other disciplines to declare to what extent they agreed with ten statements regarding their attitudes towards eprescribing. We deployed the chi-square test for testing the relationship between the country of residence of physicians and their attitudes towards eprescribing. RESULTS: We demonstrated a relationship between the country of residence of physicians and their attitudes towards eprescribing (P<0.001) for all the responses. Of the Swedish physicians, 92% regarded eprescribing as time saving, 88.1% as being safer and 96.0% as providing a better service for patients. Although less strongly supportive, the attitudes of the Austrian physicians were mainly positive. CONCLUSION: We found that the major potential success factors for the implementation of eprescribing in Sweden were saving of time for the physician, improved safety and better service for patients. The mainly positive attitudes of the Austrian physicians may enable implementation of eprescribing in due course. PMID- 20359403 TI - An analysis of healthcare providers' online ratings. AB - BACKGROUND: Many websites allow consumers to evaluate their healthcare experience yet scant data exist that explore the type and content of reviews. OBJECTIVE: To evaluate and describe online healthcare provider reviews. METHODS: We analysed 16,703 ratings on 6101 providers from four US cities. Ratings spanned five categories and an overall provider score. We also performed text analyses of narrative commentary (n = 15,952). RESULTS: Providers had a high mean score for each category (3.7-4.0 out of 5). Higher overall scores were associated with higher staff (adjusted odds ratio (aOR) 3.0, 95% CI 2.9-3.0, P < 0.01) and punctuality scores (aOR 2.1, 95% CI 2.05-2.15, P < 0.01). Review frequency was inversely associated with scores, (aOR 0.94, 95% CI 0.92-0.96, P < 0.01). Analyses of narrative commentaries revealed more positive than negative terms (P < 0.01). CONCLUSIONS: Online ratings were largely positive. Future research must discern how online surveys affect patient referrals, provider reputations and patients' perceptions of quality of care. PMID- 20359404 TI - Personal electronic health records: from biomedical research to people's health. AB - Access to web technologies and the increased bandwidth and capacity of these systems has facilitated the development of personal electronic health records (PEHRs). This conference reports the key messages from the Friends of the National Library of Medicine (FNLM) meeting on PEHRs 'From Biomedical Research to People's Health' in May 2009. The conference provided a comprehensive overview of issues and best practice for PEHR. The key messages of the conference were: PEHR have the potential to ensure equity, continuity and healthcare quality. Electronic records may allow individuals to contribute to disease surveillance, public health and research in ways that were not previously possible. We need to prepare carefully for a 'brave new world' in which a small number of commercial organisations may become trusted custodians of the planet's medical information. Ethical dilemmas are already emerging from the use of PEHRs - largely stemming from our experiences within the UK. This report links the findings of this conference with key UK and European innovations. Informaticians, in conjunction with clinicians and solution providers, should both prepare for the realities of PEHR and more formally articulate their potential benefits and risks. PMID- 20359405 TI - Accuracy of online health information about controlling childhood fever during the H1N1 influenza pandemic. PMID- 20359406 TI - Innovation in primary care for cost effective health services. PMID- 20359407 TI - Improving primary and community health services through nurse-led social enterprise. PMID- 20359408 TI - Addressing the needs of caregivers of cancer patients in general practice: a complex intervention. AB - BACKGROUND: This study aimed to develop an innovation to assist general practitioners (GPs) in Australia to proactively address the needs of caregivers of people with cancer. METHOD: Six GPs were video recorded each consulting six actor-patients in their respective practices. All cases depicted caregivers of people with cancer. The patients were instructed to complete a Needs Assessment Tool for Caregivers (NAT-C), before the consultation. Actor-patients were instructed to present the NAT-C to three of the six GPs they consulted, selected at random. Two assessors independently reviewed each consultation performance using the Leicester Assessment Package (LAP). The practitioners and actor patients focused on the value of the NAT-C and how it could be deployed to best effect in a subsequent 'stimulated recall session'. RESULTS: Thirty-four consultations were successfully recorded. The mean duration of consultations was 13 min. 47 sec. (range 6 min. 3 sec. to 22 min. 51 sec.). GPs differed in core competencies as measured by the LAP (P<0.001), range 37-92%. However, they demonstrated no significant differences in performance (LAP scores) analysed by scenario (P = 0.99). The 'generalised estimating equation' (GEE) model identified an improved LAP score in consultations in which the NAT-C was used (average of 3.3 points; 95% CI: -3.99, 10.6), after controlling for the different GPs and scenarios, but this improvement was not statistically significant (P = 0.37). The participants felt that the NAT-C was beneficial and suggested how it could be further refined. CONCLUSIONS: If this innovation had been formally tested in a randomised trial without assessing its impact on the consultation there might have been significant difficulties with administering the intervention in practice. PMID- 20359409 TI - Health information system linkage and coordination are critical for increasing access to secondary prevention in Aboriginal health: a qualitative study. AB - BACKGROUND: Aboriginal Australians have low rates of participation in cardiac rehabilitation (CR), despite having high rates of cardiovascular disease. Barriers to CR participation reflect multiple patient-related issues. However, an examination of the broader context of health service delivery design and implementation is needed. AIMS: To identify health professionals' perspectives of systems related barriers to implementation of the National Health and Medical Research Council (NHMRC) guidelines Strengthening Cardiac Rehabilitation and Secondary Prevention for Aboriginal and Torres Strait Islander Peoples. METHOD: Semi-structured interviews were conducted with health professionals involved in CR within mainstream and Aboriginal Community Controlled Health Services in Western Australia (WA). Thirty-eight health professionals from 17 services (ten rural, seven metropolitan) listed in the WA Directory of CR services and seven Aboriginal Medical Services in WA were interviewed. RESULTS: Respondents reported barriers encountered in health information management and the impact of access to CR services for Aboriginal people. Crucial issues identified by participants were: poor communication across the health care sector and between providers, inconsistent and insufficient data collection processes (particularly relating to Aboriginal ethnicity identification), and challenges resulting from multiple clinical information systems and incompatible technologies. CONCLUSIONS: This study has demonstrated that inadequate information systems and communication strategies, particularly those representing the interface between primary and secondary care, contribute to the low participation rates of Aboriginal Australians in CR. Although these challenges are shared by non-Aboriginal Australians, the needs are greater for Aboriginal Australians and innovative solutions are required. PMID- 20359410 TI - Use of information and communication technology to provide health information: what do older migrants know, and what do they need to know? AB - BACKGROUND: Governments and businesses are increasingly using the internet and mobile telephones to disseminate information about services and products. However, not all population groups have the resources and capabilities to support equality of access to and use of these technologies. While Australia's ageing population receives attention in a wide variety of literatures, the ageing migrant population has received very little attention in relation to understanding their place in the 'digital divide'. It is not known how this group gathers information used in everyday living, or what role the internet or mobile phones plays within this. At a time when the population is ageing and there is an increasing use of the internet to deliver services and information, there is little research on the effects of ethnicity, migration, socio-economic status, education or gender of older people on the use of information and communication technology (ICT). Addressing this should be a priority in Australia, which has an old and ageing population that includes many post-war migrants from non-English speaking European countries. AIMS: To analyse the views of older migrants living in South Australia with respect to their current information sources, their use of ICT and any barriers and enablers to future use of ICT for accessing health information. METHODS: A qualitative study employing eight focus groups involving 43 older Italian and Greek migrants living in the community in metropolitan or regional settings in South Australia. Interviews were held and audio-recorded and the English language components transcribed. Transcriptions were analysed manually using a grounded theory approach. RESULTS: Older migrants do not use ICT to a great extent to access information in their everyday lives, with many expressing no interest in learning how to do so. However, they access the information they need to function in society with a desired quality of life from multiple sources by various means. Sources include electronic and print media from Australia and their home countries, family and acquaintances, government departments or service providers. Many expressed a preference for receiving information as printed material or directly from another person. DISCUSSION: Governments or primary healthcare organisations planning to make health information solely available via ICT should be aware that doing so may lead to an increase in 'information exclusion' and the formation of functional knowledge deficits for older migrants. At the moment at least, our participants do not perceive any functional knowledge deficits as they engage multiple sources to access the information they need for everyday life. We recommend that governments and healthcare organisations evaluate the appropriateness of using ICT to directly provide information to older migrants and consider non-digital means or the engagement of 'information brokers' when communicating with groups identified as low or non-users of ICT. PMID- 20359411 TI - Effect of computerisation on Australian general practice: does it improve the quality of care? AB - BACKGROUND: There is an assumption expressed in literature that computer use for clinical activity will improve the quality of general practice care, but there is little evidence to support or refute this assumption. AIM: This study compares general practitioners (GPs) who use a computer to prescribe, order tests or keep patient records, with GPs who do not, using a set of validated quality indicators. METHODS: BEACH (Bettering the Evaluation and Care of Health) is a continuous national crosssectional survey of general practice activity in Australia. A sub-sample of 1257 BEACH participants between November 2003 and March 2005 were grouped according to their computer use for test ordering, prescribing and/or medical records. Linear and logistic regression analysis was used to compare the two groups on a set of 34 quality indicators. RESULTS: Univariate analyses showed that computerised GPs managed more problems; provided fewer medications; ordered more pathology; performed more Pap smear tests; provided more immunisations; ordered more HbA1c tests and provided more referrals to ophthalmologists and allied health workers for diabetes patients; provided less lifestyle counselling, and had fewer consultations with Health Care Card (HCC) holders. After adjustment, differences attributable solely to computer use were prescribed medication rates, lifestyle counselling, HCC holders and referrals to ophthalmologists. Three other differences emerged - computerised GPs provided fewer referrals to allied health workers and detected fewer new cases of depression, and fewer of them prescribed anti-depressants. Twenty-three measures failed to discriminate before or after adjustment. CONCLUSION: Deciding on 'best quality' is subjective. While literature and guidelines provide clear parameters for many measures, others are difficult to judge. Overall, there was little difference between these two groups. This study has found little evidence to support the claim that computerisation of general practice in Australia has improved the quality of care provided to patients. PMID- 20359412 TI - Inequitable distribution of human resources for health: perceptions among Thai healthcare professionals. AB - BACKGROUND: Effective delivery of health care is dependent on health manpower. In Thailand, an insufficiency of human resources relates to an inequitable distribution of healthcare professionals rather than to insufficiencies overall. Both internal and external factors influence healthcare professionals' choice of where to work, although perceptions rather than actual circumstances are more influential in their decision-making process. This inequitable distribution of healthcare professionals in Thailand affects rural areas and the provision of primary health care. OBJECTIVES: To understand the subjective perceptions, attitudes and dynamics among healthcare professionals regarding where they seek employment and the impact on the provision of primary care. DESIGN: Questionnaire survey among Thai healthcare students and professionals and semi-structured interviews with healthcare professionals investigating attitudes and perceptions. SETTING: Thai rural, urban and metropolitan areas. RESULTS: An interesting mix of factors influences healthcare professionals with regard to where they seek employment, or continue their employment. Family and community commitments, social status and a sense of belonging were associated with healthcare professionals seeking employment in their province of origin. Tensions are also emerging between preventative and curative health. These tensions, together with financial remuneration and professional development opportunities and promotions, as perceived by healthcare professionals themselves, have implications for current and future healthcare policy. CONCLUSION: The scaling up of human resources for health in Thailand will not, based on past experiences and attitudes outlined in this research, ensure an equitable distribution of healthcare professionals. Further consideration of these professionals' expectations of being able to work in areas close to their families and of sufficient financial remuneration is required. It is likely that rural regions and the delivery of primary care will be negatively affected by continued inequities. It was also found that current healthcare policies are creating new tensions. PMID- 20359414 TI - Antenatal services for Aboriginal women: the relevance of cultural competence. AB - BACKGROUND: Due to persistent significantly poorer Aboriginal perinatal outcomes, the Women's and Newborns' Health Network, Western Australian Department of Health, required a comprehensive appraisal of antenatal services available to Aboriginal women as a starting point for future service delivery modelling. A services audit was conducted to ascertain the usage frequency and characteristics of antenatal services used by Aboriginal women in Western Australia (WA). METHODS: Telephone interviews were undertaken with eligible antenatal services utilising a purpose specific service audit tool comprising questions in five categories: 1) general characteristics; 2) risk assessment; 3) treatment, risk reduction and education; 4) access; and 5) quality of care. Data were analysed according to routine antenatal care (e.g. risk assessment, treatment and risk reduction), service status (Aboriginal specific or non-specific) and application of cultural responsiveness. RESULTS: Significant gaps in appropriate antenatal services for Aboriginal women in metropolitan, rural and remote regions in WA were evident. Approximately 75% of antenatal services used by Aboriginal women have not achieved a model of service delivery consistent with the principles of culturally responsive care, with few services incorporating Aboriginal specific antenatal protocols/programme, maintaining access or employing Aboriginal Health Workers (AHWs). Of 42 audited services, 18 Aboriginal specific and 24 general antenatal services reported utilisation by Aboriginal women. Of these, nine were identified as providing culturally responsive service delivery, incorporating key indicators of cultural security combined with highly consistent delivery of routine antenatal care. One service was located in the metropolitan area and eight in rural or remote locations. CONCLUSION: The audit of antenatal services in WA represents a significant step towards a detailed understanding of which services are most highly utilised and their defining characteristics. The cultural responsiveness indicators used in the audit establish benchmarks for planning culturally appropriate antenatal services that may encourage Aboriginal women to more frequently attend antenatal visits. PMID- 20359413 TI - Facilitating uptake of Aboriginal Adult Health Checks through community engagement and health promotion. AB - BACKGROUND: Adult Health Checks (AHCs) for Aboriginal and Torres Strait Islander people (MBS Item 710) promote comprehensive physical and psychosocial health assessments. Despite the poor uptake of health assessments in Aboriginal and Torres Strait Islander people, a small number of successful implementation initiatives have been reported. In order to ensure uptake of these screening initiatives, there remains a need to demonstrate the feasibility of models of implementing AHCs. AIMS: The aim of this paper is to address the process issues and overarching outcomes of a two-day targeted screening and assessment programme to increase the uptake of AHCs at an Aboriginal Community Controlled Medical Service. METHOD: Clients of an urban Aboriginal Medical Service (AMS) were invited to undertake an AHC during a two-day screening initiative. On-site general practitioners (GPs), nurses, and Aboriginal Health Workers (AHWs) worked within a team to facilitate screenings at an AMS. Barriers and facilitators to the initiative and strategies for quality improvement were discussed by the team. A review of medical notes was undertaken six months following the screening days to document uptake of recommendations. RESULTS: Forty clients undertook AHCs as part of the initiative. In total, 113 diagnostic tests, interventions, specialist referrals and medication initiatives had been enacted within the following six months as a result of screening day visits. Benefits to individual clients, the community, the AMS and staff were identified. CONCLUSIONS: The screening day demonstrated feasibility and acceptability of this approach and provides support for its implementation in other health facilities. Importantly, this service was provided in a culturally sensitive framework and within an interdisciplinary teamwork model. This targeted approach increased uptake of assessment items and provided opportunities for health advice and risk factor modification. PMID- 20359415 TI - Learning to write. PMID- 20359416 TI - Evaluating the effects of coaching to improve motivational interviewing skills of dental hygiene students. AB - PURPOSE: Motivational Interviewing (MI) is a style of encouraging and supporting patients in making their own choices in matters concerning their health. MI is emerging in health care as a viable strategy for enhancing a patient's intrinsic motivation to change self care. The purpose of this pilot study was to determine the effects and level of incorporation of coaching to improve MI adherence of dental hygiene students' patient education presentations as measured by parts of the Motivational Interviewing Integrity Coding System (MITI) and Motivational Interviewing Skills Code (MISC). METHODS: A convenience sample of second year dental hygiene students from a Midwestern community college were invited to participate in the study. This pilot study utilized a pre- and post-test design to evaluate the effect of coaching to improve MI scores of students. Students were audio taped during 2 brief patient education sessions. Upon completion of the first tape, students received feedback and coaching in MI and then made a second tape of a brief patient education encounter. RESULTS: Student subjects changed behavior scores in the direction appropriate to MI following coaching on most measures. Summary scores indicate an improvement in the use of open questions, complex reflections and MI adherence, but not in change talk or reflections-to-questions ratio. CONCLUSIONS: The use of coaching sessions improved the skills of dental hygiene students learning MI-adherent behaviors. PMID- 20359417 TI - Halitosis: a review of current literature. AB - PURPOSE: Halitosis is defined as an unpleasant odor that emanates from the oral cavity with intra-oral and/or extra-oral origins. Fifty percent of people worldwide view themselves as having halitosis, with 90% of the etiology being intra-oral. Dental hygiene practitioners should be knowledgeable about the current classifications, diagnosis and treatment modalities to best meet the needs of patients either self-reporting or diagnosed with this problem. Classification of halitosis, assessment, diagnosis, intra-oral and systemic contributing factors, treatment, management and clinical application are discussed in this review. PMID- 20359419 TI - Application of a conceptual framework for distance learning in dental hygiene education and allied health disciplines. AB - PURPOSE: Distance education (DE) and distance learning (DL) technologies use continues to experience exponential, global growth. Various DE delivery platforms are being used for dental hygiene and allied health programs offered in post secondary education. However, a need exists to analyze factors of program and student success using DL modalities. Administrators and educators should consider building educational programs on sound pedagogical principles when using DL for their delivery mechanism. This paper offers an applied conceptual framework as a model when developing DE/DL programs for preparing professionals in dental hygiene and allied health careers. PMID- 20359418 TI - An analysis of student performance benchmarks in dental hygiene via distance education. AB - PURPOSE: Three graduate programs, 35 undergraduate programs and 12 dental hygiene degree completion programs in the United States use varying forms of Distance Learning (DL). Relying heavily on DL leaves an unanswered question: Is learner performance on standard benchmark assessments impacted when using technology as a delivery system? A 10 year, longitudinal examination looked for student performance differences in a Distance Education (DE) dental hygiene program. The purpose of this research was to determine if there was a difference in performance between learners taught in a traditional classroom as compared to their counterparts taking classes through an alternative delivery system. METHODS: A longitudinal, ex post facto design was used. Two hundred and sixty-six subject records were examined. Seventy-seven individuals (29%) were lost through attrition over 10 years. One hundred and eighty-nine records were used as the study sample, 117 individuals were located face-to-face and 72 were at a distance. Independent variables included time and location, while the dependent variables included course grades, grade point average (GPA) and the National Board of Dental Hygiene Examination (NBDHE). Three research questions were asked: Were there statistically significant differences in learner performance on the National Board of Dental Hygiene Examination (NBDHE)? Were there statistically significant differences in learner performance when considering GPAs? Did statistically significant differences in performance exist relating to individual course grades? T-tests were used for data analysis in answering the research questions. RESULTS: From a cumulative perspective, no statistically significant differences were apparent for the NBDHE and GPAs or for individual courses. CONCLUSIONS: Interactive Television (ITV), the synchronous DL system examined, was considered effective for delivering education to learners if similar performance outcomes were the evaluation criteria. PMID- 20359420 TI - Oral health knowledge attitudes and behaviors of migrant preschooler parents. AB - PURPOSE: The purpose of the study was to establish baseline data about oral health knowledge, attitudes and behaviors of migrant and seasonal farm workers (MSFW). The study focused on MSFWs that are parents of preschool-aged children, and who utilized services at 3 migrant dental clinics. METHODS: An oral health knowledge attitudes and behaviors survey was developed and pilot tested in 2006. The resulting 34 item survey was administered by trained promotores de salud (community health workers) to 45 parents of preschoolers (15 at each clinic site) served by 3 migrant dental clinics. Parents answered questions as they pertained to their oldest preschooler (up to age 5). RESULTS: Dental visits in the last 12 months were reported for 26 (58%) of the children. Fifteen parents (33%) had a dental visit in the last year. Thirty-five parents (77/8%) reported their child's oral health to be good, and 21 (46.7%) reported their own to be good. Half of the children were enrolled in Head Start (HS). Of those, 18 (79%) had a dental visit in the last year, whereas 8 (36%) of those not enrolled in HS had a visit. Discrepancies existed for the age parents believed children should stop using a bottle and the age they actually did stop using a bottle. There were discrepancies in knowledge about decay causing drinks and consumption of drinks by preschool-aged children. CONCLUSIONS: MSFWs remain an underserved population with poor access to oral health care and multiple factors affecting oral health knowledge, attitudes and behaviors. A better understanding of influences on oral health knowledge, attitudes and behaviors within the population can assist in implementing appropriate interventions for the maintenance of good oral health in MSFW families. HS can have a positive impact on oral health for MSFW children. PMID- 20359421 TI - Factors affecting North Carolina dental hygienists' confidence in providing obesity education and counseling. AB - PURPOSE: Obesity is a major public health issue in the United States. Dental hygienists influence their patients' oral health by providing dietary and behavioral recommendations that encourage good oral health practices. However, it is not known if they are ready to provide behavioral counseling strategies for weight loss. This study investigates whether dental hygienists in North Carolina are confident to counsel patients who are at-risk for obesity. METHODS: A questionnaire was used to survey 246 dental hygienists attending a continuing education (CE) course. It investigated self-reported confidence in providing obesity counseling, educational preparation, outcome expectations and self efficacy. The primary outcome was confidence in providing weight loss counseling. Mantel Haenszel statistics were used to compare group of interest. RESULTS: Of the dental hygienists surveyed, 43% perceived an increase of overweight patients in their practices. Nearly all (95%) felt that dental hygienists have a role in helping patients improve nutrition. Over half (65%) expressed confidence in discussing obesity-related health risks. On average, the confidence in getting patients to follow weight loss advice was significantly different (p=0.02) for those with a 2 year degree and those with a 4 year degree. CONCLUSIONS: The findings indicate that many North Carolina dental hygienists are willing to discuss obesity with patients. PMID- 20359422 TI - Informed consent. PMID- 20359423 TI - Pediatric oral health-related quality of life improvement after treatment of early childhood caries: a prospective multisite study. AB - PURPOSE: This study's purpose was to compare changes in parent-reported pediatric oral health-related quality of life between children with early childhood caries (ECC) and children who were caries-free; the ECC children received surgical dental intervention between baseline and follow-up. METHODS: A newly developed self-report instrument, the POQL, was administered to 501 parents of 2- to 8-year old children (caries-free=315; ECC=186) in hospital dental clinics in Columbus, Ohio, and Washington, D.C. RESULTS: At baseline, ECC children were more likely to have fair or poor oral health and were rated as having more pain and trouble with physical, mental, and social functioning due to their teeth or mouth vs caries free children (P<.001). At 6 and 12 months following dental treatment for ECC, there were significant improvements in parental ratings of their children's oral health status and a significant reduction in problems reported with physical, mental, and social functioning (all P<.001). CONCLUSIONS: Compared with caries free children, early childhood caries children were more likely to have worse questionnaire response scores and to experience greater negative impacts on physical, mental, and social functioning. Dental interventions in ECC children had a significant positive impact on parental ratings of their overall oral health and physical, mental, and social functioning. PMID- 20359424 TI - Flowable glass ionomer cement as a liner: improving marginal adaptation of atraumatic restorative treatment restorations. AB - PURPOSE: The present study aims to evaluate the in vitro microleakage of two layers GIC proximal restorations in primary molars. METHODS: Forty primary molars received proximal cavity preparations and were randomly divided in two groups. G1 was restored with a regular powder/liquid ratio GIC. G2 firstly received a flowable layer of GIC and secondly a regular GIC layer. After 24h water storage (37 degrees C), the teeth were made impermeable with the exception of the restoration area and 1 mm of their surrounding, immersed in 0.5% methylene blue solution (4h), rinsed and sectioned mesio-distally. One side was polished and analyzed under light microscope. Replicates from the other side were observed under SEM. Microleakage evaluation was carried out by 3 evaluators. RESULTS: The data analysis (Mann-Whitney) showed a significant (P<0.01) better result for G2. Regarding the SEM evaluation, irregularities were observed in the G1 at the tooth/GIC interface. For G2, it was not possible to observe any displacement of the GIC in relation to the tooth structure, which confirmed better adaptation as seen in the microleakage test. CONCLUSION: the insertion of a flowable GIC layer in proximal cavities before the insertion of a regular GIC layer improves the material adaptation to the tooth. PMID- 20359425 TI - Comparison of the retentive strength of 3 different posts in restoring badly broken primary maxillary incisors. AB - PURPOSE: The management of mutilated primary incisors in early childhood caries is a clinical challenge and necessitates the use of intraradicular retention. This study's purpose was to compare the retentive strength of 3 different types of posts in restoring broken primary incisors: (1) composite posts; (2) orthodontic "gamma" wire posts; and (3) glass fiber posts. METHODS: This vitro study was performed on 30 extracted human primary maxillary incisors. Samples were randomly divided into 3 groups of 10 each: group 1 (composite posts and composite core); group 2 (orthodontic "gamma" wire posts and composite core); and group 3 (glass fiber posts and composite core). Mounted specimens were subjected for tensile strength on an Instron testing machine. The values were statistically analyzed. RESULTS: Mean tensile strength values for glass fiber posts was 5.89+/ 0.66 kg force, followed by 4.46+/-0.82 and 3.56+/-0.53 kg force for orthodontic wire posts and composite posts, respectively, with a statistically significant difference between and within the groups (P<.01). Groups 1 and 2 showed more bulk cohesive failure and less adhesive bond failure. Group 3 showed only adhesive bond failure. CONCLUSION: Glass fiber posts showed greater dislodging strength, followed by orthodontic "gamma" wire posts and, least of all, composite posts. PMID- 20359426 TI - Evaluation of chlorhexidine on the quality of the hybrid layer in noncarious primary teeth: an in vitro study. AB - It has recently been observed that chlorhexidine has the capacity to inhibit matrix metalloproteinase. Therefore, the object of this study was to assess the effect of chlorhexidine on the quality of the hybrid layer of noncarious primary teeth. In group 1, the teeth were subjected to acid-etching, chlorhexidine application, Single Bond adhesive insertion, and restoration with resin composite Z250. Group 2 received the same procedures, without the application of the antimicrobial agent. Twenty-five regions were examined by scanning electronic microscopy by blind examiners. The data obtained were statistically analyzed by the chi-square and student t tests at a 5% level of significance. The groups presented few interfacial gaps without statistically significant differences. Group 1 presented a larger number of areas with a visible hybrid layer (68%) vs group 2 (52%). The layer's thickness was 3.33 microm and 3.28 microm for groups 1 and 2, respectively (P=.94). The results showed that the clinical restorative protocol with the use of chlorhexidine application does not interfere significantly in the morphological characteristics of the hybrid layer. PMID- 20359427 TI - Marginal microleakage of alternative restorative treatment and conventional glass ionomer restorations in extracted primary molars. AB - PURPOSE: The objective of this study was to compare the marginal leakage of cervical glass ionomer restorations made using alternative restorative treatment (ART) and conventional restoration techniques. METHODS: Twenty primary molars with Class V carious dentin on the buccal surfaces were prepared using ART, and a second set of 20 noncarious molars had Class V preparations made with a high speed handpiece. The occlusal margin was located in enamel and the gingival margin in dentin/cementum. All teeth were restored with high-density glass ionomer cement (GIC; Fuji IXgp) according to manufacturers' instructions, thermally stressed for 300 cycles, and stained with methylene blue. Samples were sectioned and evaluated for microleakage. RESULTS: One-way analysis of variance revealed no statistically significant difference between leakage at margins of ART and conventional restorations. (P=.92) There was no significant difference between leakage at the enamel and dentin margins. CONCLUSIONS: Alternative restorative treatment with high-density glass ionomer cement provides enamel and dentin margins that show marginal leakage comparable to conventionally restored primary teeth. These results show the potential of ART in conjunction with high density GIC in providing treatment for children and adolescents in situations where traditional cavity preparation and restoration is not possible. PMID- 20359428 TI - Novel cathepsin C mutation in a Brazilian family with Papillon-Lefevre syndrome: case report and mutation update. AB - PURPOSE: Papilion-Lefevre syndrome (PLS) is a rare autosomal recessive disorder that involves palmoplantar keratosis (PK) and severe aggressive periodontitis. Cathepsin C (CTSC) gene mutations are etiologic for PLS, with more than 60 different mutations reported in different ethnic groups worldwide. The purpose of this study was to report a novel cathepsin C mutation in a Brazilian patient. METHODS: A 4-year-old boy presented with aggressive periodontitis, recession, missing teeth, and hyperkeratosis of the palms of hands and soles. Peripheral blood samples were obtained from family members for genomic DNA isolation. The coding region and exon/intron boundaries of the CTSC gene were amplified and sequenced. RESULTS: The patient had a PLS phenotype, which included PK and early onset severe periodontitis. Sequence analysis showed a novel CTSC mutation (c.267 268del) present in the homozygous state. CONCLUSION: This report described a novel mutation in a family with Brazilian Papillon-Lefevre syndrome and presented a review of all cathepsin C (65) mutations reported to date. PMID- 20359429 TI - Coronal pulp dimensions in noncarious and restored deciduous second molars: a radiovisiographic study. AB - PURPOSE: The purpose of this study was to measure the coronal pulp dimensions in primary maxillary and mandibular second molars and to evaluate the influence on restorative procedures on them. METHODS: Included in this study were 80 4-7 year old male and female patients with occlusal or proximal restorations on primary maxillary or mandibular second molars and with noncarious antimeres. Radiovisiographic images were captured utilizing standard bitewing radiographs via the parallel cone technique. Morphometric analysis was performed using Dexis and AutoCAD 2000 software, and data was analyzed using student's t test (unpaired). RESULTS: A significant difference was found in crown and coronal pulp dimensions in noncarious (sound) primary maxillary and mandibular second molars, even though no significant reductions were found in restored primary second molars. CONCLUSIONS: Crown and coronal pulp dimensions were significantly greater in noncarious primary mandibular second molars than in maxillary second molars. The mesiodistal crown width of maxillary molars was greater in males than in females. Nonsignificant reductions were observed in amalgam restored primary maxillary and mandibular second molars over a period of six months. No significant difference in pulpal dimensions was observed when Class I restorations were compared with Class II restorations in either arch. PMID- 20359430 TI - Knowledge and attitudes toward dental avulsion of public and private elementary schoolteachers. AB - PURPOSE: The purpose of this study was to evaluate and compare the knowledge and attitudes toward dental avulsion of public and private elementary schoolteachers. METHODS: the study was performed by applying a questionnaire in a sample composed of 95 elementary schoolteachers (46 from public schools and 49 from private schools). The questionnaire comprised 9 questions and was pretested before final implementation. RESULTS: Thirty-nine percent of private schoolteachers and 15% of public schoolteachers witnessed at least 1 case of dental avulsion at the school (P=.009). Ninety-two percent and 62% of private and public schoolteachers, respectively, admitted the possibility of an avulsioned tooth to be reimplanted (P<.001). Both responses were statistically different when school type (public or private) was considered. Only 27% of private schoolteachers and 11% of public schoolteachers knew the procedures to be taken in cases of avulsed teeth, and more than 95% of all teachers did not feel capable of executing tooth reimplantation. The study showed no statistical difference between private and public schoolteachers' knowledge. CONCLUSIONS: Teachers and other professionals involved in children's care and supervision must be correctly and well informed about dental avulsion, its consequences and the correct procedures to be performed in such cases. PMID- 20359431 TI - Oral and dental findings in a child with growth hormone insensitivity syndrome. AB - Growth hormone insensitivity syndrome, also known as Laron syndrome, is an autosomal recessive disorder caused by defects the of growth hormone receptor gene and may lead to increased growth hormone levels. This syndrome's main clinical features are: dwarfism; acromicria; organomicria; cervical spinal stenosis; early osteoarthritic changes of the atlantoaxial joint; small oropharynx; decreased growth velocity; insulin resistance; hypoglycemia; delayed skeletal maturation and osteoporosis; and muscular and central nervous tissue underdevelopment. The facial bones, especially sphenoid and mandibular, are also underdeveloped. No reports of the incidence of growth hormone insensitivity syndrome in the population are available in the literature. The purpose this case report was to describe oral findings and particularities of dental treatment in a child with growth hormone insensitivity syndrome. PMID- 20359432 TI - Management of a dentigerous cyst in a child with hereditary angioedema. AB - The purpose of this paper was to report the case of an 8-year-old girl with hereditary angioedema (HAE) who underwent 2 oral surgeries for removal of a dentigerous cyst without any significant episode of angioedema. One week after routine radiographic examination revealed an odontogenic cyst, short-term prophylactic therapy (Danazol 600 mg/day) was initiated to avoid an angioedema attack. The cyst was carefully removed under general anesthesia without life threatening complications. Postoperative prophylactic therapy also was performed. Histopathological exam confirmed the diagnosis of a dentigerous cyst. Nine months after surgery, the cyst recurred and it was successfully removed once more under general anesthesia. The same prophylactic therapy was used, this time with fresh frozen plasma. The case presented showed that the oral management of a pediatric patient with HAE is a high-risk procedure. It can be performed successfully, however, when the involved health professionals are aware of both the risks and preventive strategies. PMID- 20359433 TI - Prognostic significance of absolute lymphocyte count and lymphocyte subsets in lymphomas. AB - Lymphocytopenia is a poor prognostic marker in initial staging of non- Hodgkin lymphomas (below 1.0 x 10(9)/l) and Hodgkin lymphoma (below 0.6 x 10(9)/l) and in relapsed diffuse large B cell lymphoma. Early lymphocyte recovery > or =0.5 x 10(9)/l after autologous and allogeneic stem cell transplantation is a significant predictor of tumor control and survival in lymphomas. Natural killer cells are involved in tumor cell killing and are the only subset of lymphocytes associated with disease outcome in initial staging and after autologous stem cell transplantation in lymphomas. The antitumor effect of various NK cell subsets should be defined. PMID- 20359434 TI - Premenstrual dysphoric disorder--review of actual findings about mental disorders related to menstrual cycle and possibilities of their therapy. AB - It is known that mood disorders in women explicitly relates to estrogen production. Except for these findings phenomenon as Premenstrual Syndrome and Premenstrual Dysphoric Disorder, directly connected to menstrual cycle in women, is widely discussed. Premenstrual dysphoric disorder (PMDD) is a set of subjectively unpleasant mental and somatic symptoms. It appears in luteal phase of ovarian cycle. During menstruation it remits and disappears up to one week from its termination. DSM IV classified PMDD into the category of "Other specific depressive disorders" and further revision DSM IV-TR classifies PMDD as a separate strictly defined psychiatric diagnosis. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) does not include any specific category as PMDD or similar. The closest category F38.8 does not represent the core of the phenomenon because it relates only to general depressive symptomatology and does not give specific diagnostic criteria to menstrual cycle related mood disorders (Grady-Weliky, 2003). In the presented article, possible effectivity of PMDD treatment with the focus to antidepressants of SSRI type (Serotonin selective reuptake inhibitors) is discussed. In spite of interesting and significant findings, the treatment of PMDD and accordingly PMS is above all multidisciplinary question and it must be treated like that. PMID- 20359435 TI - Our experience with surgical treatment of tympanojugular pragangliomas. AB - Tympanojugular paragangliomas are benign and slow growing lesions of the lateral skull base. Due to their localization and vascularity, they represent a surgical challenge. Treatment modalities include preoperative embolization of feeding vessels and tumour itself, surgical removal and irradiation. In our group, 16 patients with large tympanojugular paragangliomas have been operated in the period of 10 years. Surgical radicality has been achieved in 62.5%, in the rest of patients the tumour remnants were either irradiated with a Leksell gamma knife, or left without treatment in a wait-end-rescan approach. According to the benign character of the tumour, radicality is not always the highest goal, since a radical removal may be compromised by a high postoperative morbidity. PMID- 20359437 TI - Comparison of three methods for determination of glucose. AB - Study refers comparison of three methods for glucose determination - precision (repeatability, reproducibility), traceability to SRM 965a NIST, comparability in blood-pools and in patients' samples: Electrochemical determination on Super GL (DiaSys, Germany) in hemolyzate - GL method, spectrophotometric determination using hexokinase (Glucose System Reagent 800, Olympus) - HKL method - and using glucose dehydrogenase (Glucose Gluc-DH, EcolineS+, DiaSys, Germany) - GDL method in hemolyzate. For showing differences between the concentration of glucose in hemolyzed blood and corresponding plasma, spectrophotometric determination using hexokinase in plasma was used (Glucose System Reagent 800, Olympus) - HKP method. Coefficients of variation characterizing precision under repeatability and reproducibility conditions are not higher than 3.0% for the GL method, 6.3% for the GDL method and 15.8% for the HKL method with low sensitivity. For glucose concentration less than 8 mmol/l, HKL tends to give lower results than GDL, and GL tends to give higher results than GDL. For glucose concentration about 2 mmol/l, the results of glucose in plasma - HKP method - tend to be significantly lower (by more than ten percent) than in corresponding total (hemolyzed) blood. HKL method can be reasonably used in a high number of parallel determinations. For glucose 8 mmol/l and lower, comparability of results given by HKL, GDL and GL methods gradually worsens, while for glucose between 8 and 34 mmol/l results of the three mentioned methods are well comparable. PMID- 20359436 TI - Association between human papilloma virus-type infections with micronuclei frequencies. AB - To determine the association between Human papillomavirus (HPV)-type infections with the frequency of Micronucleus (MN), a hospital-based, unmatched case-control study was carried out. We evaluated and compared the average number of MN/1,000 cells among three groups of Mexican females. Twenty one women ranging in age from 31-56 years and divided into three groups were studied. Group I comprised seven control women without cervical lesions and with HPV-negative, Group II was composed of seven women with Squamous intraepithelial lesions (SIL) infected with low-risk HPV low-risk, and Group III was made up of seven women with SIL infected with high-risk HPV infection. Analysis of variance (ANOVA) test revealed differences among Groups I (5.14+/-3.02), II (13.43+/-3.41), and III (25.43+/ 3.41) (F=67.46; P=0.0001). We demonstrated an association between HPV type infection and higher MN frequencies. However, a larger controlled study with sufficient follow-up will be required to further evaluate the usefulness of this test in the clinical management of women with HPV infection. PMID- 20359438 TI - Magnesium and posthypoxic changes of nitrergic population in rat hippocampus. AB - We used NADPH-diaphorase staining to study effects of magnesium pre-treatment during long-lasting hypoxia on the brain structure of rats. NADPH-diaphorase is an enzyme co-localized in neurons with NO-synthase that is responsible for NO synthesis. NO participates in hypoxic-ischaemic injury of the brain. Hypoxia was induced in consecutive days from the 2nd till the 11th day of postnatal life in a hypobaric chamber (for 8 hours per day). Magnesium was administered before each hypoxia exposition. At the age of 12 days, the animals were transcardially perfused with 4% buffered neutral paraformaldehyde under the deep thiopental anaesthesia. Cryostat sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in five hippocampal regions. In comparison to the control animals, intermittent hypoxia brought about higher density of NADPH diaphorase positive neurons in all studied areas of the hippocampal structure: in CA1 and CA3 areas of the hippocampus and in hilus, in the dorsal and ventral blades of the dentate gyrus. Magnesium pre-treatment during hypoxia reduced number of NADPH-diaphorase positive neurons in all studied areas. PMID- 20359439 TI - Adhesive bowel strangulation after caesarean section, the rare puerperal complication. AB - Caesarean section is the most frequent abdominal operation carried out in obstetric practice. Parturients undergoing this operation are still exposed to a substantial rate of short- and long-term complications. The incidence of re laparotomy after caesarean section is 0.12-0.70%. The most common indication for re-laparotomy is intra-abdominal bleeding, uterine atony, eventration, haematoma in the muscle and intra-abdominal abscesses. We present the case report of an unusual life-threatening complication of caesarean section that led to re laparotomy. Caesarean section rate has been continually increasing globally in the last few decades, thus we also have to take into account unusual complications e.g. intestinal complication. PMID- 20359440 TI - Acute pancreatitis after viperid snake cerastes cerastes envenoming: a case report. AB - Snakebites by the viper snake Cerastes cerastes are quite common across the world but rarely published with regard to their mostly benign course. The reported case study depicts the envenoming of a 36-year-old Czech man, a private herpetologist, who suffered snakebite to his finger. He developed a painful local reaction with hemorrhagic oedema. Subsequently, consumption coagulopathy with thrombocytopenia and haemolysis, colicky pain in the epigastrium and acute renal failure developed. Acute exudative pancreatitis was diagnosed on the third day after envenoming. Hemorrhagic oedema of the arm was complicated by a phlegmon. Symptomatic treatment including haemodialysis, fresh frozen plasma and thrombocytes was administered. Antivenom was not administered due to the delay in referral to the specialized unit. The patient recovered within one month, only postnecrotic defects of the finger persisted. PMID- 20359441 TI - A giant villous adenoma: case mimicking rectosigmoid malignancy; radiological survey to diagnosis. AB - Villous adenomas are benign lesions, which are difficult to interpret because of their malignancy potential. They have similar radiological findings to malignant lesions. Usually, villous adenomas are asymptomatic although they may cause rectal bleeding like malignant tumours. We present a case of giant villous adenoma to evaluate the contribution of its radiological features including double contrast barium enema, computed tomography and magnetic resonance imaging examinations for the differential diagnosis. PMID- 20359442 TI - Micro- and macrovascular complications among Greenlanders and Danes with type 2 diabetes mellitus in Nuuk, Greenland. AB - OBJECTIVES: To estimate the prevalence of micro- and macrovascular complications and risk factors among Greenlanders and Danes with type 2 diabetes mellitus (T2DM) in Nuuk, Greenland. STUDY DESIGN: Observational and cross-sectional study, based on a review of medical records and patient interviews. METHODS: Review of the electronic medical records and interviews obtained from T2DM patients connected to the Center of Primary Health Care in Nuuk. RESULTS: A total of 123 patients (81 Greenlanders and 42 Danes) with T2DM for a mean of 6 years were included. Fifty-seven percent of the Greenlanders were diagnosed within the last 3 years. Ninety-one percent of the patients had BMI>or=25 kg/m(2), 42% had 1 or more first-degree relatives with diabetes, 43% were current smokers, 69% were categorized as leading a very physically active lifestyle and 60% described a healthy diet pattern. Sixty-eight percent of all the patients suffered from at least 1 complication - 51% neuropathy, 14% retinopathy, 10% macrovascular complication and 43% microalbuminuria. The number of complications was significantly correlated to the duration of diabetes (p=0.008) and low physical activity (p=0.037). Retinopathy was correlated to Danish ethnicity (p=0.020). CONCLUSION: The majority of the Greenlandic patients (57%) were diagnosed within the last 3 years, which may indicate either the beginning of an epidemic or an increased awareness of T2DM, or both. The high prevalence of microvascular complications and risk factors such as smoking and microalbuminuria are a matter of concern. Efforts to reduce smoking and increase physical activity could be considered as prime targets for initiatives. PMID- 20359443 TI - Ethnicity, self-reported health, discrimination and socio-economic status: a study of Sami and non-Sami Norwegian populations. AB - OBJECTIVES: Investigate the association between ethnicity, social factors and self-reported health conditions of Sami and non-Sami Norwegian populations. STUDY DESIGN: Cross-sectional questionnaire. METHODS: SAMINOR is a population-based study of health and living conditions that was conducted in 24 municipalities in northern Norway during 2003 and 2004. The present study included 12,265 individuals aged between 36 and 79, whose ethnicity was categorized as Sami (33.1%), Kven (7.8%) and Norwegian majority population (59.1%). RESULTS: Sami respondents reported inferior health conditions in comparison to the Norwegian majority population. The most unsatisfactory conditions were reported by Sami females living outside the defined Sami area (with greater integration and assimilation) (p<0.05). Females typically reported less favourable health conditions than did males. Health inequalities varied by age and were more apparent in persons aged in their mid-50s or above. Across ethnic groups, respondents with the highest education and household income were healthier than others. Furthermore, those reporting to have been frequently discriminated against were more likely to report poorer health than those who did not; the odds ratios (95% CI) was found to be 2.88 (1.92-4.32) for women and 1.61 (1.08-2.42) for men. When discrimination was included in the logistical model, the increased risk of poor self-reported health decreased to non-significance for Sami respondents. The estimated risk decreased further when the socio-economic status was taken into account. CONCLUSIONS: The findings of this study suggest that self reported ethnic discrimination combined with low socio-economic status contributes to inequalities in self-reported health when Sami and Norwegian majority population are compared. PMID- 20359444 TI - [Periodontal diagnosis in orthodontics]. AB - Before any orthodontic treatment can begin, it is essential that the patient's periodontium be in sound condition, capable of responding to the movement of teeth in a healthy fashion. Inspection of the dentition, palpation of tissues, and careful study of adequate X-Rays are all necessary for establishing a diagnosis, but review of the depth of gingival pockets with periodontal probes is the key procedure for avoiding blunders in treatment. After periodontal health has been validated, it is vital that orthodontists determine the patient's periodontal biotype by clinical observation and periodontal probing and assess the quality of the gingival attachments of the teeth that will be affected by the expansion forces of treatment. The ensemble of these criteria will dictate what treatment paths and forces the orthodontist will employ. PMID- 20359445 TI - [Er:YAG laser in periodontics and implication in the orthodontic treatment plan]. AB - The Er:YAG laser is used in periodontal surgery to remove excess tissue formations and to clean periodontal pockets. Combined with ultrasonic procedures lasers have significantly advanced the parameters of periodontal surgery. The goal of this article is to review the working mechanisms of the Er:YAG laser in the wide variety of its applications in complex treatment situations in both periodontics and orthodontics. PMID- 20359446 TI - [Contribution of orthodontics in treatment planning patients with reduced periodontium]. AB - Orthodontics is the planned movement of teeth that can be carried thanks to the provoked resorption and apposition of osseous tissue. From the standpoint of the periodontium orthodontists should always be cognizant of the risk of iatrogenically weakening soft tissue status but at the same time they should consider that an improved character of the periodontium is one of the benefits that can be derived from mechano-therapy. These periodontal improvements, in the broadest sense of the term, can result from traditional overall therapy as well as treatment aimed solely at a local condition requiring extrusion of a tooth or, more rarely, alveolar distraction. PMID- 20359447 TI - [Plaque control, a key element of successful orthodontics]. AB - It is mainly because of periodontal tissues and, more particularly, the periodontal ligament that the orthodontist is able to move teeth. According the ratio cost/benefit/security, the orthodontist needs to prevent and/or to avoid the deleterious effects of its treatments on periodontal tissues. Gingival inflammation with a high hyperplasia compound, periodontal attachment loss, bone loss and root resorption may result, in absolute value, in a reduction of periodontal support. The key to prevent these problems is plaque control, phase too often neglected. The challenge before any orthodontic treatment, both in children or in adults, is to change the behavior of the patient concerning the mouth and the dental plaque. The aim of this paper is to explore the evidence based literature (systematic revues, meta-analysis), to provide thought elements and concrete proposals to definitely resolve this critical phase of orthodontic treatment that is the motivation, phase that can also be achieved by "dental auxiliaries". PMID- 20359448 TI - [Reciprocal relationships between orthodontics and periodontics: relevance of a synergistic action]. AB - The aim of this article is to review evidence on the reciprocal relationships between orthodontics and periodontics. Normal intra-arch and inter-arch relationships have long been considered as an anatomic prerequisite for the preservation of dental health and function. Certain malocclusion traits are associated with difficulties in maintaining good oral hygiene and as a consequence to poor periodontal condition. Therefore, proper alignment of the teeth provided by orthodontic treatment may promote good control of soft deposit and calculus and subsequent periodontal inflammation. The tendency of orthodontic appliances, particularly the brackets and bands to promote the accumulation of plaque and thus increasing the risk of developing localized periodontal disease must however be constantly emphasized. Periodontitis involves progressive loss of the alveolar bone around the teeth, pathological tooth migration and gingival recession with pathological tooth migration and gingival recession as a possible outcome. The effectiveness of orthodontics in conjunction with periodontics in the management of these esthetic and functional defects is highlighted in this review. PMID- 20359450 TI - [Diagnosis and treatment of temporo-mandibular disorders in orthodontics]. AB - Orthodontists are fully prepared to treat the problems of occlusion that they are called upon to deal with every day. On the other hand temporo-mandibular joint disorders present more obscure difficulties from the point of view of detection and diagnosis as well the management of their treatment. That is why a profound understanding of the anatomical and physiological functioning of the temporo mandibular joint has become indispensable for today's orthodontists who are now asked to detect and diagnose an assortment of TMJ disturbances whose etiology may vary greatly. By performing a rigorous diagnostic procedure, based on a thorough clinical examination supported by careful axiographic and radiological studies, of temporo-mandibular malfunctioning and its underlying etiological causes, which are primarily dento-alveolar and occlusal in nature, orthodontists will be able to adopt an appropriate therapeutic approach that might be purely orthodontic or multi-disciplinary and carried out with the collaboration of specialists in occlusion, oral surgery, and even osteopathy. PMID- 20359451 TI - [Can orthodontic treatment generate temporomandibular disorders and pain? A review]. AB - While considered for years to play the primary role in the etiology of temporo mandibular joint disturbances (TMD), occlusal discrepancies are now considered to be just one causative factor among many. Recent studies, literature reviews or meta-analyses, and longitudinal studies with follow-up of children treated for many years all conclude that there is no risk of orthodontic treatment giving rise to episodes of temporo-mandibular disorders. The signs of TMD appearing during the course of orthodontic treatment should be considered in the context of the epidemiology of the disorder, which is characterized by a strong increase in its occurrence during adolescence. In conclusion, it should be stated that if orthodontic treatment can no longer be considered as one of the etiopathogenic factors in the TMD complex, there are no scientific arguments to justify the converse, that there are indications for orthodontic treatment whose sole goal would be the treatment of TMD. PMID- 20359454 TI - Production of biofuels from synthesis gas using microbial catalysts. AB - World energy consumption is expected to increase 44% in the next 20 years. Today, the main sources of energy are oil, coal, and natural gas, all fossil fuels. These fuels are unsustainable and contribute to environmental pollution. Biofuels are a promising source of sustainable energy. Feedstocks for biofuels used today such as grain starch are expensive and compete with food markets. Lignocellulosic biomass is abundant and readily available from a variety of sources, for example, energy crops and agricultural/industrial waste. Conversion of these materials to biofuels by microorganisms through direct hydrolysis and fermentation can be challenging. Alternatively, biomass can be converted to synthesis gas through gasification and transformed to fuels using chemical catalysts. Chemical conversion of synthesis gas components can be expensive and highly susceptible to catalyst poisoning, limiting biofuel yields. However, there are microorganisms that can convert the CO, H(2), and CO(2) in synthesis gas to fuels such as ethanol, butanol, and hydrogen. Biomass gasification-biosynthesis processing systems have shown promise as some companies have already been exploiting capable organisms for commercial purposes. The discovery of novel organisms capable of higher product yield, as well as metabolic engineering of existing microbial catalysts, makes this technology a viable option for reducing our dependency on fossil fuels. PMID- 20359452 TI - Zoonotic hepatitis E: animal reservoirs and emerging risks. AB - Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1 4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown. PMID- 20359455 TI - Microbial naphthenic Acid degradation. AB - Naphthenic acids (NAs) are an important group of trace organic pollutants predominantly comprising saturated aliphatic and alicyclic carboxylic acids. NAs are ubiquitous; occurring naturally in hydrocarbon deposits (petroleum, oil sands, bitumen, and crude oils) and also have widespread industrial uses. Consequently, NAs can enter the environment from both natural and anthropogenic processes. NAs are highly toxic, recalcitrant compounds that persist in the environment for many years, and it is important to develop efficient bioremediation strategies to decrease both their abundance and toxicity in the environment. However, the diversity of microbial communities involved in NA degradation, and the mechanisms by which NAs are biodegraded, are poorly understood. This lack of knowledge is mainly due to the difficulties in identifying and purifying individual carboxylic acid compounds from complex NA mixtures found in the environment, for microbial biodegradation studies. This paper will present an overview of NAs, their origin and fate in the environment, and their toxicity to the biota. The review describes the microbial degradation of both naturally occurring and chemically synthesized NAs. Proposed pathways for aerobic NA biodegradation, factors affecting NA biodegradation rates, and possible bioremediation strategies are also discussed. PMID- 20359456 TI - Surface and adhesion properties of lactobacilli. AB - The surface properties of lactobacilli are of significant technological importance as they determine the interaction of the bacterial cells with the gastrointestinal mucosa, and therefore influence their location in the gut and their functionality. Studying the surface of the bacteria is critical for understanding the adhesion process better. This review compiles the knowledge from studies on the characterization Lactobacillus surfaces and evaluates the potential relationship between the cells' physicochemical characteristics and their adhesive abilities. It also discusses the effect that the production processes, such as fermentation and drying, can exert on the surface properties and adhesion abilities of lactobacilli. PMID- 20359457 TI - Shining light on the microbial world the application of Raman microspectroscopy. AB - Raman microspectroscopy is a noninvasive, label-free, and single-cell technology for biochemical analysis of individual mammalian cells, organelles, bacteria, viruses, and nanoparticles. Chemical information derived from a Raman spectrum provides comprehensive and intrinsic information (e.g., nucleic acids, protein, carbohydrates, and lipids) of single cells without the need of any external labeling. A Raman spectrum functions as a molecular "fingerprint" of single cells, which enables the differentiation of cell types, physiological states, nutrient condition, and variable phenotypes. Raman microspectroscopy combined with stable isotope probing, fluorescent in situ hybridization, and optical tweezers offers a culture-independent approach to study the functions and physiology of unculturable microorganisms in the ecosystem. Here, we review the application of Raman microspectroscopy to microbiology research with particular emphasis on single bacterial cells. PMID- 20359458 TI - Detection of invasive aspergillosis. AB - Invasive aspergillosis (IA) caused by the fungus Aspergillus fumigatus is a frequent and life-threatening complication of chemotherapy and bone marrow transplantation with high rates of mortality and morbidity. Diagnosis of IA is complex and can only be confirmed by identification of the fungus in biopsy samples. Capturing tissue for diagnosis is in itself hazardous, and because of this many patients receive empirical antifungal treatment rather than undergo biopsy. However, the treatment carries with it significant side effects and is prohibitively expensive. Because of this, attempts have been made to develop specific and sensitive diagnostic tests that can be used to track the early onset of infection and permit rational administration of antifungal drugs. Early attempts at nonculture-based diagnosis using human immune serum to detect circulating Aspergillus antigens proved unreliable, and so focus turned to hybridoma technology and the use of monoclonal antibodies (MAbs) to detect signature molecules of infection. Detection of one such signature molecule, galactomannan (and associated galactomannoprotein molecules), forms the basis of the commercial Platelia enzyme immunoassay (EIA), an assay that has found widespread use in IA diagnosis. Nevertheless, concerns surrounding its accuracy mean that alternative strategies to diagnosis have been sought including detection of the fungal cell wall component (1-->3)-beta-d-glucan and polymerase chain reaction (PCR). The poor specificity of "panfungal" (1-->3)-beta-d-glucan tests and current lack of standardization of PCR assays have led to the recent development of next-generation MAb-based assays that detect surrogate markers of infection and that have been incorporated into "point-of-care" diagnostic devices. This chapter examines the development of antibody-antigen, (1-->3)-beta d-glucan, and nucleic acid-based approaches to IA detection, current concerns surrounding accurate disease diagnosis, and how animal models of infection can be used to inform assay development and validation. PMID- 20359453 TI - Thermostable enzymes as biocatalysts in the biofuel industry. AB - Lignocellulose is the most abundant carbohydrate source in nature and represents an ideal renewable energy source. Thermostable enzymes that hydrolyze lignocellulose to its component sugars have significant advantages for improving the conversion rate of biomass over their mesophilic counterparts. We review here the recent literature on the development and use of thermostable enzymes for the depolymerization of lignocellulosic feedstocks for biofuel production. Furthermore, we discuss the protein structure, mechanisms of thermostability, and specific strategies that can be used to improve the thermal stability of lignocellulosic biocatalysts. PMID- 20359459 TI - Bacteriophage host range and bacterial resistance. AB - Host range describes the breadth of organisms a parasite is capable of infecting, with limits on host range stemming from parasite, host, or environmental characteristics. Parasites can adapt to overcome host or environmental limitations, while hosts can adapt to control the negative impact of parasites. We consider these adaptations as they occur among bacteriophages (phages) and their bacterial hosts, since they are significant to phage use as antibacterials (phage therapy) or to protection of industrial ferments from phage attack. Initially, we address how phage host range can (and should) be defined plus summarize claims of host ranges spanning multiple bacterial genera. Subsequently, we review bacterial mechanisms of phage resistance. These include adsorption resistance, which results in reduced interaction between phage and bacterium; what we describe as "restriction," where bacteria live but phages die; and abortive infections, where both phage and bacterium die. Adsorption resistance includes loss of phage receptor molecules on hosts as well as physical barriers hiding receptor molecules (e.g., capsules). Restriction mechanisms include phage genome uptake blocks, superinfection immunity, restriction modification, and CRISPR, all of which function postphage adsorption but prior to terminal phage takeover of host metabolism. Standard laboratory selection methods, involving exposure of planktonic bacteria to high phage densities, tend to directly select for these prehost-takeover resistance mechanisms. Alternatively, resistance mechanisms that do not prevent bacterium death are less readily artificially selected. Contrasting especially bacteria mutation to adsorption resistance, these latter mechanisms likely are an underappreciated avenue of bacterial resistance to phage attack. PMID- 20359460 TI - Psb30 contributes to structurally stabilise the Photosystem II complex in the thermophilic cyanobacterium Thermosynechococcus elongatus. AB - A deletion mutant that lacks the Psb30 protein, one of the small subunits of Photosystem II, was constructed in a Thermosynechococcus elongatus strain in which the D1 protein is expressed from the psbA(3) gene (WT*). The DeltaPsb30 mutant appears more susceptible to photodamage, has a cytochrome b(559) that is converted into the low potential form, and probably also lacks the PsbY subunit. In the presence of an inhibitor of protein synthesis, the Psb30 lost more rapidly the water oxidation function than the WT* under the high light conditions. These results suggest that Psb30 contributes to structurally and functionally stabilise the Photosystem II complex in preventing the conversion of cytochrome b(559) into the low potential form. Structural reasons for such effects are discussed. PMID- 20359461 TI - Photoelectrochemical control of the balance between cyclic- and linear electron transport in photosystem I. Algorithm for P700+ induction kinetics. AB - Redox transients of chlorophyll P700, monitored as absorbance changes DeltaA810, were measured during and after exclusive PSI excitation with far-red (FR) light in pea (Pisum sativum, cv. Premium) leaves under various pre-excitation conditions. Prolonged adaptation in the dark terminated by a short PSII+PSI- exciting light pulse guarantees pre-conditions in which the initial photochemical events in PSI RCs are carried out by cyclic electron transfer (CET). Pre excitation with one or more 10s FR pulses creates conditions for induction of linear electron transport (LET). These converse conditions give rise to totally different, but reproducible responses of P700- oxidation. System analyses of these responses were made based on quantitative solutions of the rate equations dictated by the associated reaction scheme for each of the relevant conditions. These provide the mathematical elements of the P700 induction algorithm (PIA) with which the distinguishable components of the P700+ response can be resolved and interpreted. It enables amongst others the interpretation and understanding of the characteristic kinetic profile of the P700+ response in intact leaves upon 10s illumination with far-red light under the promotive condition for CET. The system analysis provides evidence that this unique kinetic pattern with a non responsive delay followed by a steep S-shaped signal increase is caused by a photoelectrochemically controlled suppression of the electron transport from Fd to the PQ-reducing Qr site of the cytb6f complex in the cyclic pathway. The photoelectrochemical control is exerted by the PSI-powered proton pump associated with CET. It shows strong similarities with the photoelectrochemical control of LET at the acceptor side of PSII which is reflected by release of photoelectrochemical quenching of chlorophyll a fluorescence. PMID- 20359462 TI - Phosphatidyl alcohols: effect of head group size on domain forming properties and interactions with sterols. AB - In this study, we have examined the membrane properties and sterol interactions of phosphatidyl alcohols varying in the size of the alcohol head group coupled to the sn-3-linked phosphate. Phosphatidyl alcohols of interest were dipalmitoyl derivatives with methanol (DPPMe), ethanol (DPPEt), propanol (DPPPr), or butanol (DPPBu) head groups. The Phosphatidyl alcohols are biologically relevant, because they can be formed in membranes by the phospholipase D reaction in the presence of alcohol. The melting behavior of pure phosphatidyl alcohols and mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or cholesterol was assessed using high sensitivity differential scanning calorimetry (DSC). DPPMe had the highest melting temperature ( approximately 49 degrees C), whereas the other phosphatidyl alcohols had similar melting temperatures as DPPC ( approximately 40 41 degrees C). All phosphatidyl alcohols, except DPPMe, also showed good miscibility with DPPC. The effects of cholesterol on the melting behavior and membrane order in multilamellar bilayer vesicles were assessed using steady-state anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and DSC. The ordering effect of cholesterol in the fluid phase was lower for all phosphatidyl alcohols as compared to DPPC and decreased with increasing head group size. The formation of ordered domains containing the phosphatidyl alcohols in complex bilayer membranes was determined using fluorescence quenching of DPH or the sterol analogue cholesta-5,7,(11)-trien-3-beta-ol (CTL). The phosphatidyl alcohols did not appear to form sterol-enriched ordered domains, whereas DPPMe, DPPEt appeared to form ordered domains in the temperature window examined (10-50 degrees C). The partitioning of CTL into bilayer membranes containing phosphatidyl alcohols was to a small extent increased for DPPMe and DPPEt, but in general, sterol interactions were weak or unfavorable for the phosphatidyl alcohols. Our results show that the biophysical and sterol interacting properties of phosphatidyl alcohols, having identical acyl chain structures, are markedly dependent on the size of the head group. PMID- 20359463 TI - Involvement of natural killer T cells in halothane-induced liver injury in mice. AB - Drug-induced liver injury (DILI) causes significant patient morbidity and mortality, and is the most common reason for drug withdrawals. It is imperative to gain a thorough understanding of the underlying mechanisms of DILI to effectively predict and prevent these reactions. We have recently developed a murine model of halothane-induced liver injury (HILI). The aim of the present study was to investigate the role of hepatic natural killer T (NKT) cells in the pathogenesis of HILI. The degrees of HILI were compared between WT and CD1d(-/-) mice, which are deficient in NKT cells. The data revealed that CD1d(-/-) mice were resistant in developing HILI. This resistance appeared to be a direct result of NKT cell depletion rather than an indirect one due to the absence of cross talk between NKT cells and other hepatic innate immune cells. Compared with WT mice, CD1d(-/-) mice exhibited a significantly lower number of hepatic infiltrating neutrophils upon halothane challenge (470,000+/-100,000/liver in WT vs. 120,000+/-31,500/liver in CD1d(-/-) mice). This result in conjunction with our previous finding of an indispensable role of neutrophils in HILI strongly suggests that NKT cells play a critical role in regulating neutrophil recruitment, thereby contributing to the development of HILI. Collectively, the current study and published reports indicate that this murine model of HILI provides an experimental system for the investigation of the underlying mechanisms of DILI. In addition, this model may yield the discovery of susceptibility factors that may control the development of liver injury in patients treated with halothane and potentially other drugs. PMID- 20359464 TI - Carbonylation of myosin heavy chains in rat heart during diabetes. AB - Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later the animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for 6 weeks, while the other group received no treatment. After 8 weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca(2+)- and Mg(2+)-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-alpha to MHC-beta ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-alpha and MHC-beta. Aminoguanidine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca(2+)-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. PMID- 20359466 TI - Anti-amyloidogenic effect of AA3E2 attenuates beta-amyloid induced toxicity in SK N-MC cells. AB - Beta-amyloid peptide (Abeta) is believed to play a recognized role in pathogenesis of Alzheimer's disease (AD). Self-association of Abeta peptide into amyloid fibrils causes neurotoxicity. Compounds capable of interfering with Abeta Abeta interaction through binding to nucleation sites can inhibit Abeta amyloidogenesis and Abeta-induced cytotoxicity. AA3E2 is a triazine-derivative whose anti-amyloidogenic ability has previously been established. In the present study, we evaluated the protective effect of AA3E3 against Abeta(1-42)-induced toxicity in SK-N-MC cell line. The cell exposure to the co-incubated Abeta(1-42) with AA3E2 decreased the cell viability loss dose-dependently, compared to cells exposed to Abeta(1-42) fibrils. Co-incubation with AA3E2 also attenuated the ROS production, activation of caspase-3 and the extent of apoptotic cell death induced by Abeta(1-42) fibril. Moreover, the 3D structure of the molecular associates between Abeta(1-42) and AA3E2 were theoretically determined by docking studies. Our docking data indicated that AA3E2 inhibits the formation of Abeta fibril likely via binding to the nucleation site within the hydrophobic region of Abeta (KLVFF). These observations provide the background for future design of more elegant beta-breaking agents for dissolution of Abeta fibrillar aggregates. PMID- 20359465 TI - An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice. AB - It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr(-/-)) mice may alter cardiovascular homeostasis in adulthood. We tested the hypothesis that blood pressure regulation in adult heterozygous mice (ahr(+/-)) would be normal, compared to ahr(-/-) mice, since no vascular abnormalities have been reported in the heterozygote animals. Mean arterial blood pressure (MAP) was measured using radiotelemetry prior to and during treatment with inhibitors of the autonomic nervous system, nitric oxide synthase (NOS), angiotensin converting enzyme (ACE), or endothelin-1 A receptor (ET(A)). Also, indices of renin-angiotensin system (RAS) activation were measured. ahr(+/-) and ahr(-/-) mice were normotensive and hypotensive, respectively, compared to wild type (ahr(+/+)) littermates. Responses of all genotypes to autonomic nervous system inhibition were normal. ahr(+/-) mice responded normally to NOS inhibition, while the responses of ahr(-/-) mice were significantly blunted. In contrast, ahr(+/-) mice were significantly more responsive to inhibition of ACE, an ET(A) antagonist, or both, while ahr(-/-) mice were significantly less responsive to ACE inhibition and more responsive to an ET(A) antagonist. ahr(+/-) mice also exhibited significant increases in plasma renin and ACE activity, plasma sodium, and urine osmolality, indicative of RAS activation. Thus, normotension in ahr(+/-) mice appears to be maintained by increased RAS and ET-1 signaling, while hypotension in ahr(-/-) mice may result from decreased RAS signaling. In conclusion, despite the lack of overt fetal vascular abnormalities in ahr(+/-) mice, the loss of a single ahr allele has a significant effect on blood pressure regulation. PMID- 20359467 TI - Evolution of cholinesterases in the animal kingdom. AB - Cholinesterases emerged from a family of enzymes and proteins with adhesion properties. This family is absent in plants and expanded in multicellular animals. True cholinesterases appeared in triploblastic animals together with the cholinergic system. Lineage specific duplications resulted in two acetylcholinesterases in most hexapods and in up to four genes in nematodes. In vertebrates the duplication leading to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is now considered to be an ancient event which occurred before the split of osteichthyes. The product of one or the other of the paralogues is responsible for the physiological hydrolysis of acetylcholine, depending on the species lineage and tissue considered. The BChE gene seems to have been lost in some fish lineages. The complete genome of amphioxus (Branchiostoma floridae: cephalochordate) contains a large number of duplicated genes or pseudogenes of cholinesterases. Sequence comparison and tree constructions raise the question of considering the atypical ChE studied in this organism as a representative of ancient BChE. Thus nematodes, arthropods, annelids, molluscs, and vertebrates typically possess two paralogous genes coding for cholinesterases. The origin of the duplication(s) is discussed. The mode of attachment through alternative C-terminal coding exons seems to have evolved independently from the catalytic part of the gene. PMID- 20359468 TI - Location of chlorhexidine in DMPC model membranes: a neutron diffraction study. AB - Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. It is known to partition into phospholipid bilayers of aqueous model-membrane preparations. Neutron diffraction data taken at 36 degrees C on the location of CHX in phosphatidylcholine (PC) bilayers is presented. The center of mass of the deuterated hydrocarbon chain of CHX is found to reside 16A from the center of the bilayer in 1,2-dimyristoyl-sn glycero-3-phosphatidylcholine (14:0-14:0PC). This places the drug near the glycerol backbone of the lipid, and suggests a mode of action whereby the molecule is bent in half and inserts wedge-like into the lipid matrix. This mechanism is distinct from detergent-like mechanisms of membrane disruption and more similar to some anti-microbial peptide action, where peptides insert obliquely into the bilayer headgroup region to disrupt its structure. PMID- 20359469 TI - Intraindividual variability of thyroid function tests in a pediatric population. PMID- 20359470 TI - External quality assessment of multi-analyte chromatographic methods in oral fluid. AB - BACKGROUND: A proficiency testing scheme was set up for the DRUID (Driving under the influence of Drugs, Alcohol and Medicines) research project, funded by the European Commission, in which oral fluid is analysed by eleven laboratories. A common collection and analysis methodology is used: Statsure Saliva Sampler is used for collection and LC-MS/MS or GC-MS confirmation analysis of 22 substances is performed on all samples. Despite internal validation and quality control samples, external quality assessment is still necessary to further increase comparability of results. Four rounds of proficiency testing (PT) were organized between March 2008 and September 2009. METHODS: Qualitative results were evaluated using sensitivity and specificity. Quantitative results were evaluated using z-scores and the standard deviation of Horwitz. RESULTS: Specificity was above 99% in each round, sensitivity per analyte varied between 81.7 and 100%, and 20 out of 22 analytes had a sensitivity above 90%. The percentage of satisfactory z-scores increased from 79.4% to 89.2%. This trend was seen for all drug classes, except zopiclone. Results were discussed with participating laboratories and problems were addressed. CONCLUSIONS: Because of these corrective actions, DRUID laboratories have a lower variation in results than previously published PT schemes in oral fluid. PMID- 20359471 TI - Association of biochemical parameters and RAGE gene polymorphisms in healthy infants and their mothers. AB - BACKGROUND: The receptor for advanced glycation end-products (RAGEs) and its gene polymorphisms are implicated in the pathogenesis of different chronic diseases including diabetes and its complications. Infant formulas contain high amounts of advanced glycation end-products (AGEs) - the ligands of RAGE. METHODS: In this cross-sectional study, we examined the impact of G82S and -374 A/T polymorphisms in the gene encoding RAGE on standard blood chemistry, soluble (s)RAGE and inflammatory markers in 244 healthy infants (3-16months of age) and in 119 healthy mothers. Children were subdivided according to age (younger and older than 8months) and for the -374 A/T polymorphism according to the feeding regimen (breast-fed vs. infant formula-fed). RESULTS: Minor allele of the RAGE gene polymorphism G82S was associated with reduced plasma sRAGE in all age groups and with increased sICAM-1 in older children and mothers. Minor allele carrying mothers had decreased insulin sensitivity and HDL. The A allele of the RAGE gene promoter polymorphism -374 A/T was associated with higher indices of insulin resistance in young infant formula-fed, but not breast-fed children. In older, formerly infant formula-fed children signs of insulin resistance diminished, while formerly breast-fed children with A allele were more insulin sensitive. CONCLUSIONS: The phenotype of minor allele carriers in G82S is associated with reduced levels of protective sRAGE in healthy infants. With increasing age sICAM 1 levels increased and insulin resistance developed. In early childhood the phenotype of the -374 A/T polymorphism was diet-dependently associated with changes in glucose metabolism, which diminished with increasing age. PMID- 20359472 TI - A spectral phenotype of oncogenic human papillomavirus-infected exfoliative cervical cytology distinguishes women based on age. AB - BACKGROUND: Human papillomavirus (HPV) is a sexually-transmitted infection associated with cervical cancer. Of over 100 HPV types identified, 13 are high risk oncogenic. In unvaccinated women worldwide, the incidence of cervical cancer from HPV16 and HPV18 will remain. Cervical cytology can be graded from normal (atypia-free) to low-grade to high-grade. Infrared (IR) spectroscopy is a non destructive technique that allows the acquisition of a biochemical-cell fingerprint based on vibrational states of chemical bonds. METHODS: Exfoliative cervical cytology specimens (n=147) were retrieved, graded by a cytologist and HPV-tested/genotyped using hybrid capture 2 and the Roche HPV Linear Array. Additionally, the spectral signatures of cervical cell lines C33A, HeLa and SiHa were examined. After washing, cellular material was transferred to low-E glass slides and interrogated using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Given the complex nature of the dataset consisting of thousands of variables (wavenumbers), we used multivariate analysis for data reduction and information retrieval. Principal component analysis coupled with linear discriminant analysis (PCA-LDA) generated a visual representation of the data (scores plot) and, identification of the wavenumbers and consequent biochemical entities responsible for segregation (loadings plot). RESULTS: Immortalised cell lines were readily distinguishable from each other. It was difficult to segregate categories of cytology associated with HPV infection types. However, in low-grade cytology infected with high-risk oncogenic HPV16 or HPV18, it was possible to segregate women based on whether they were aged 20 29years vs. 30-39years. CONCLUSIONS: Our findings suggest a spectral phenotype in exfoliative cervical cytology associated with transient vs. persistent HPV infection. PMID- 20359473 TI - Direct non-radioactive assay of galactose-1-phosphate:uridyltransferase activity using high performance liquid chromatography. AB - BACKGROUND: Galactose-1-phosphate:uridyltransferase (GALT) catalyses the conversion of galactose-1-phosphate (Gal-1-P) and UDP-glucose (UDP-Glc) into glucose-6-phosphate and UDP-galactose (UDP-Gal). Complete, or near complete, deficiency of GALT causes classic galactosaemia. The diagnosis is confirmed by measuring GALT activity in erythrocytes. The most commonly used assays require radio labelled substrates or indirect coupled assays. METHODS: GALT activity was measured in erythrocyte lysates using optimal concentrations of the substrates galactose-1-phosphate and UDP-Glc. UDP-Gal and UDP-Glc were separated using reversed-phase high performance liquid chromatography with UV detection. Clinical validity was assessed using blood samples from galactosaemic patients. RESULTS: UDP-Gal and UDP-Glc were separated with HPLC. The assay was linear with incubation times up 80 min and between 0 and 42.5 nmol haemoglobin. Within-day and between-day imprecision at 50, 75 and 100% enzyme activity was <1.4% and <2.4%, respectively. Mean GALT activity in 33 individuals was 601+/-79 nmol UDP Gal/(micromol Hb.h) (range 492-697). Patients with classical galactosaemia were easily detected by their extremely low activity. CONCLUSIONS: We have developed a reliable and convenient direct method to measure GALT activity in human erythrocytes using HPLC with UV detection. PMID- 20359474 TI - Evaluation of the Sysmex UF1000i flow cytometer for ruling out bacterial urinary tract infection. AB - BACKGROUND: Urine culture is one of the most frequently requested tests in microbiology, and it represents the gold standard for the diagnosis of UTIs. Considering the high prevalence of negative results and the long TAT of the culture test, the use of a rapid and reliable screening method is becoming more and more important, as it reduces the workload, the TAT of negative results, and above all, unnecessary antibiotic prescription. METHODS: The Sysmex UF1000i is a new urine flow cytometry analyzer capable of quantifying urinary particles, including BACT, WBCs, and YLCs. To evaluate the analytical performance of the UF1000i as a method for ruling out UTIs, we examined 1349 urine samples and compared the UF1000i results with standard urine culture results. RESULTS: With instrument cut-off values of 170BACTx10(6)/L and 150WBCsx10(6)/L, we obtained a sensitivity of 98.8%, a specificity of 76.5%, a NPV of 99.5%, and four false negative results (1.2%), avoiding the culture of 57.1% of samples. CONCLUSION: The Sysmex UF1000i was capable of improving the efficiency of a routine microbiology laboratory by processing 100samples/h and providing negative results in a few minutes, thus reducing unnecessary testing with an acceptable number of false negative results. In addition, the preliminary evaluation of B_FSC and B_FLH parameters from bacteria histograms seems to be useful for the distinction of bacterial strains detected (Gram-negatives versus Gram-positives). In fact when B_FSC was less than 30 ch, it allowed the distinction of Gram-negative bacteria in 97% of the samples. PMID- 20359475 TI - Proteomics-based identification of haptoglobin as a novel plasma biomarker in oral squamous cell carcinoma. AB - BACKGROUND: Identification of tumor biomarkers to assist early diagnosis and monitoring of disease progression may potentially decrease the mortality and morbidity associated with oral cancer. METHODS: A mouse model with oral squamous cell carcinoma (OSCC) induced by 4-nitroquinoline 1-oxide (4-NQO)/arecoline in drinking water was established to discover stage-associated biomarkers. A proteomics approach, immunoblot and immunohistochemical analysis were used to validate the expressed biomarkers in mice with OSCC. Human plasma samples were also collected and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay. RESULTS: Proteomic profiling of mouse plasma samples indicated that haptoglobin and apolipoprotein A1 precursor were up-regulated in the mice with OSCC. Immunoblotting of plasma samples and immunohistochemical analysis of oral tissues showed a significantly higher level of haptoglobin in the OSCC mice than in the control mice. The expression of haptoglobin in human plasma samples from 52 patients with OSCC indicated a strong correlation between the increasing levels of haptoglobin and the clinical stages of OSCC (P<0.01). CONCLUSIONS: These results suggest that haptoglobin has a great potential as a sensitive plasma biomarker for early detection of patients with OSCC. PMID- 20359476 TI - Genetic evidence that SOST inhibits WNT signaling in the limb. AB - SOST is a negative regulator of bone formation, and mutations in human SOST are responsible for sclerosteosis. In addition to high bone mass, sclerosteosis patients occasionally display hand defects, suggesting that SOST may function embryonically. Here we report that overexpression of SOST leads to loss of posterior structures of the zeugopod and autopod by perturbing anterior-posterior and proximal-distal signaling centers in the developing limb. Mutant mice that overexpress SOST in combination with Grem1 and Lrp6 mutations display more severe limb defects than single mutants alone, while Sost(-/-) significantly rescues the Lrp6(-/-) skeletal phenotype, signifying that SOST gain-of-function impairs limb patterning by inhibiting the WNT signaling through LRP5/6. PMID- 20359477 TI - Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis. AB - Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity. PMID- 20359478 TI - Changes in extracellular pH affect glycine receptor channels expressed in HEK 293 cells. AB - Glycine receptors are expressed throughout the central nervous system working for inhibitory neurotransmission. Since fluctuations of the blood pH value occur under certain physiological and pathological conditions, we investigated the influence of the extracellular pH on glycine homomeric and heteromeric receptor functions using patch clamp in combination with the fast agonist application technique. Our results demonstrated that both alpha1 homomeric and alpha 1 beta heteromeric glycine receptors were remarkably inhibited under acidic extracellular pH. Under alkaline extracellular pH 8.5, there was also a negative functional effect. Desensitization was accelerated depending on pH and a rebound current was observed at an extremely acidic pH value. In double-pulse experiments on alpha1 homomeric receptors, a more rapid recovery of the glycinergic current was shown at pH 4.5 compared to current induced at a physiological pH of 7.2. Our study provided a potential cause for the impaired function of the glycine receptor channels during pH fluctuations occurring in the central nervous system, especially under pathological conditions such as epileptic seizure or ischaemia. PMID- 20359479 TI - Mitochondria: Their role in ganglion cell death and survival in primary open angle glaucoma. AB - Retinal ganglion cell axons within the globe are functionally specialised being richly provided with many mitochondria. Mitochondria produce the high energy that is required for nerve conduction in the unmylenated part of the ganglion cell axons and for the maintenance of optimum neuronal function. We proposed that in the initiation of glaucoma (POAG) an alteration in the quality of blood flow dynamics in the optic nerve head results in sustained or intermittent ischemia of a defined nature. This results in normal mitochondrial function being negatively affected and as a consequence retinal ganglion cell function is compromised. Ganglion cells in this state are now susceptible to secondary insults which they would normally tolerate. One secondary insult to ganglion cell mitochondria in such a state might be light entering the eye. Other insults to the ganglion cells might come from substances such as glutamate, prostaglandins and nitric oxide released from astrocytes and microglia in the optic nerve head region. Such cascades of events initiated by ischemia to the optic nerve head region ultimately cause ganglion cells to die at different rates. PMID- 20359480 TI - Growth factors and chemotactic factors from parasitic helminths: molecular evidence for roles in host-parasite interactions versus parasite development. AB - For decades molecular helminthologists have been interested in identifying proteins expressed by the parasite that have roles in modulating the host immune response. In some cases, the aim was targeting parasite-derived orthologues of mammalian cytokines and growth factors known to have functions in immune modulation. In others, novel proteins without homology to mammalian cytokines were isolated by investigating effects of purified worm extracts on various immunological processes. Often, the role parasite-derived growth factors play in worm development was ignored. Here, we review growth factors and chemotactic factors expressed by parasitic helminths and discuss their recognised and potential roles in immunomodulation and/or parasite development. PMID- 20359481 TI - Processing and secretion of ROP13: A unique Toxoplasma effector protein. AB - Like most intracellular pathogens, Toxoplasma synthesizes and secretes an arsenal of proteins to successfully invade its host cell and hijack host functions for intracellular survival. The rhoptries are key secretory organelles that inject proteins into the host cell where they are positioned to co-opt host processes, although little is known regarding how these proteins exert their functions. We show here that the rhoptry protein ROP13 is synthesized as a pre-pro-protein that is processed in the parasite. Processing occurs at a conserved SphiXE cleavage site as mutagenesis of glutamic acid to alanine at the P1 position disrupts ROP13 maturation. We also demonstrate that processing of the prodomain is not necessary for rhoptry targeting and secretion. While gene disruption reveals that ROP13 is not essential for growth in fibroblasts in vitro or for virulence in vivo, we find that ROP13 is a soluble effector protein that can access the cytoplasm of host cells. Exogenously expressed ROP13 in human cells remains cytosolic but also appears toxic, suggesting that over-expression of this effector protein is disrupting some function within the host cell. PMID- 20359482 TI - Genetic characterisation of uninucleated cyst-producing Entamoeba spp. from ruminants. AB - Six ssrRNA gene sequences were obtained by PCR amplification of DNA from uninucleated Entamoeba cysts isolated from fresh faeces of sheep, cows, a roe deer and a reindeer. Phylogenetic analysis using sequences of non-, uni-, quadri- and octonucleate cyst-producing Entamoeba spp. for comparison showed that all six isolates formed a separate clade nested within the clade of quadrinucleate cyst producers. The data indicate that Entamoeba bovis can be isolated from ruminant hosts other than cattle, and we suggest that organisms clustering with the sheep and cattle isolates analysed in the present study be named E. bovis. PMID- 20359483 TI - Molecular architecture of the Mn2+-dependent lactonase UlaG reveals an RNase-like metallo-beta-lactamase fold and a novel quaternary structure. AB - The ulaG gene, located in the ula regulon, is crucial for the catabolism of l ascorbate under anaerobic conditions and it has been proposed to encode for the putative l-ascorbate-6-P lactonase. The ulaG gene is widespread among eubacteria, including human commensal and pathogenic genera such as Escherichia, Shigella, Klebsiella and Salmonella. Here, we report the three-dimensional structures of the apoenzyme and Mn(2+) holoenzyme of UlaG from E. coli to 2.6 A resolution, determined using single-wavelength anomalous diffraction phasing and molecular replacement, respectively. The structures reveal a highly specialized metallo beta-lactamase-like fold derived from an ancient structural template that was involved in RNA maturation and DNA repair. This fold has a novel quaternary architecture consisting of a hexameric ring formed by a trimer of UlaG dimers. A mononuclear Mn(2)(+)-binding site resides at the core of the active site, which displays micromolar affinity for Mn(2+) and a distorted trigonal bipyramidal coordination. The active site Mn(2+) ion can be replaced by Co(2+) or Zn(2+), but not by Fe(3+). We further show that the Mn(2+) or Co(2)(+)-loaded enzyme exhibits lactonase activity towards l-ascorbate 6-P, thereby providing the first direct evidence of its catalytic role in the L-ascorbate catabolic pathway. Guided by the structural homology, we show that UlaG is able to cleave phosphodiester linkages in cyclic nucleotides, suggesting that the conservation of the fold and of the key catalytic residues allows for the evolutionary acquisition of substrate specificity for novel but related substrates. PMID- 20359484 TI - Crystal structure of the leucine aminopeptidase from Pseudomonas putida reveals the molecular basis for its enantioselectivity and broad substrate specificity. AB - The zinc-dependent leucine aminopeptidase from Pseudomonas putida (ppLAP) is an important enzyme for the industrial production of enantiomerically pure amino acids. To provide a better understanding of its structure-function relationships, the enzyme was studied by X-ray crystallography. Crystal structures of native ppLAP at pH 9.5 and pH 5.2, and in complex with the inhibitor bestatin, show that the overall folding and hexameric organization of ppLAP are very similar to those of the closely related di-zinc leucine aminopeptidases (LAPs) from bovine lens and Escherichia coli. At pH 9.5, the active site contains two metal ions, one identified as Mn(2+) or Zn(2+) (site 1), and the other as Zn(2+) (site 2). By using a metal-dependent activity assay it was shown that site 1 in heterologously expressed ppLAP is occupied mainly by Mn(2+). Moreover, it was shown that Mn(2+) has a significant activation effect when bound to site 1 of ppLAP. At pH 5.2, the active site of ppLAP is highly disordered and the two metal ions are absent, most probably due to full protonation of one of the metal-interacting residues, Lys267, explaining why ppLAP is inactive at low pH. A structural comparison of the ppLAP-bestatin complex with inhibitor-bound complexes of bovine lens LAP, along with substrate modelling, gave clear and new insights into its substrate specificity and high level of enantioselectivity. PMID- 20359485 TI - Crystal structure of yeast FAD synthetase (Fad1) in complex with FAD. AB - Flavin adenine dinucleotide (FAD) synthetase is an essential enzyme responsible for the synthesis of FAD by adenylation of riboflavin monophosphate (FMN). We have solved the 1.9 A resolution structure of Fad1, the yeast FAD synthetase, in complex with the FAD product in the active site. The structure of Fad1 shows it to be a member of the PP-ATPase superfamily. Important conformational differences in the two motifs involved in binding the phosphate moieties of FAD compared to the Candida glabrata FMNT ortholog suggests that this loop is dynamic and undergoes substantial conformational changes during its catalytic cycle. PMID- 20359486 TI - Modeling fimbriae mediated parasite-host interactions. AB - Type 1 fimbriae are a known virulence factor in a number of pathogenic enterobacteriaceae, including Salmonella, Shigella and E. coli. Yet, they are also expressed by some commensal strains, notably of E. coli. One hypothesis of the role of fimbriae in commensals is that they evoke a small but tolerable host immune response in order to have the host release sialic acid, which is a valuable nutrient. Genetic evidence suggests that sialic acid down-regulates fimbriation. This has been believed to enable the cells to reduce virulence when the host response is increasing, thus avoiding a full activation of host defenses. In this article we assess the plausibility of this hypothesis using mathematical models. Our models lead us to two main conclusions: A slight activation of host defenses is only possible with a carefully tuned set of parameters, whereas under a wide range of parameters and assumptions, the model predicts the host defenses to be activated to at least half their potential in response to fimbriation. Secondly, the fact that fimbriation is suppressed by sialic acid seems irrelevant for the global qualitative properties. PMID- 20359487 TI - Effects of a standardized oral fat load on vascular remodelling markers in healthy subjects. AB - The most adequate way to experimentally reproduce the post-prandial lipemia condition appears to be the administration of a standardized oral fat load (OFL) to fasting patients. We studied the effects of a standardized OFL on markers of vascular remodelling in healthy subjects. We enrolled 286 Caucasians aged >or= 18 of either sex. The OFL was given after a 12-h fast. Blood samples were drawn before and 3, 6, 9 and 12h after the fat load. The following parameters were evaluated: body mass index (BMI), blood glucose (BG), systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid profile, nitrites and nitrates, adiponectin (ADP), metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). High density lipoprotein-cholesterol (HDL-C) decrease was present in subjects after 6h. Triglycerides (Tg) change was observed after 6h. Nitrites/nitrates variation was observed after 6 and 9h during OFL. Adiponectin level was decreased after 6 and 9h during OFL. Both MMP-2 and MMP-9 levels were higher after 6h during OFL. We observed that nitrites/nitrates and ADP significantly decreased and MMP-2 and MMP-9 significantly increased after a standardized OFL. Other studies need to confirm the direct acute effects of post-prandial lipemia on vascular damage. PMID- 20359488 TI - Molecular interactions of progesterone derivatives with 5 alpha-reductase types 1 and 2 and androgen receptors. AB - The aim of this study was to ascertain the inhibitory effect of several progesterone derivatives for 5 alpha-reductase types 1 and 2 isozymes and to determine the binding to the androgen receptor. The 3,20-dioxopregna-4-ene-17 alpha-yl acetate 4 containing an acetoxy group in C-17 and steroid 17 alpha hydroxypregn-4-ene-3,20-dione 5 having a hydroxyl group in the same position inhibited both isozymes. On the other hand, 17 alpha-hydroxy-4,5-epoxypregnan 3,20-dione 6 with an epoxy function at C-4, inhibited only the type 1 enzyme. Steroid 4-chloro-17 alpha-hydroxypregn-4-ene-3,20-dione 7a and 4-bromo-17 alpha hydroxypregn-4-ene-3,20-dione 7b having the C-4 conjugated system and a chlorine or a bromine atom at C-4 respectively, inhibited both types of 5 alpha-reductase. These results indicate that an increase in the electronegativity of ring A produces a major inhibitory activity for 5 alpha-reductase type 1; however this increase was not observed for type 2 enzyme. When the free hydroxyl group of 7a or 7b was esterified, compounds 3,20-dioxo-4-chloropregn-4-ene-17 alpha yl-4 ethylbenzoate 8a and 3,20-dioxo-4-bromopregn-4-ene-17 alpha yl-4-ethylbenzoate 8b were obtained; these steroids inhibited only the 5 alpha-reductase type 2 enzyme. Finasteride and steroids 4, 5, 7b, 8a showed a comparable in vivo pharmacological activity, however the IC(50) values of these compounds were higher as compared to that of finasteride. These results indicated also that steroids 4, 5, 7a, and 7b bind to the androgen receptor whereas compounds 6, 8a and 8b failed to do so. The overall data from this study showed that steroids 5 and 7b bind to the AR and decreased of the growth of prostate and seminal vesicles. Moreover, 4 decreased also the growth of seminal vesicles. PMID- 20359489 TI - Synthesis, aggregation behavior and cholesterol solubilization studies of 16-epi pythocholic acid (3 alpha,12 alpha,16 beta-trihydroxy-5 beta-cholan-24-oic acid). AB - Synthesis, aggregation behavior and in vitro cholesterol solubilization studies of 16-epi-pythocholic acid (3 alpha,12 alpha,16 beta-trihydroxy-5 beta-cholan-24 oic acid, EPCA) are reported. The synthesis of this unnatural epimer of pythocholic acid (3 alpha,12 alpha,16 alpha-trihydroxy-5 beta-cholan-24-oic acid, PCA) involves a series of simple and selective chemical transformations with an overall yield of 21% starting from readily available cholic acid (CA). The critical micellar concentration (CMC) of 16-epi-pythocholate in aqueous media was determined using pyrene as a fluorescent probe. In vitro cholesterol solubilization ability was evaluated using anhydrous cholesterol and results were compared with those of other natural di- and trihydroxy bile acids. These studies showed that 16-epi-pythocholic acid (16 beta-hydroxy-deoxycholic acid) behaves similar to cholic acid (CA) and avicholic acid (3 alpha,7 alpha,16 alpha trihydroxy-5 beta-cholan-24-oic acid, ACA) in its aggregation behavior and cholesterol dissolution properties. PMID- 20359490 TI - Decoding 3D search coil signals in a non-homogeneous magnetic field. AB - We present a method for recording eye-head movements with the magnetic search coil technique in a small external magnetic field. Since magnetic fields are typically non-linear, except in a relative small region in the center small field frames have not been used for head-unrestrained experiments in oculomotor studies. Here we present a method for recording 3D eye movements by accounting for the magnetic non-linearities using the Biot-Savart law. We show that the recording errors can be significantly reduced by monitoring current head position and thereby taking the location of the eye in the external magnetic field into account. PMID- 20359492 TI - Supercontraction of dragline silk spun by lynx spiders (Oxyopidae). AB - Supercontraction is commonly considered as a functional adaptation of major ampullate gland (MA) silk to its role as the main structural material in orb webs. However, the observation of supercontraction in the dragline silk of a lynx spider species, as it is shown in this work, offers a strong support to the hypothesis that the appearance of supercontraction preceded the advent of capture webs. Moreover, the absence of proline in the sequence of dragline silk spidroin in Oxyopidae and related spiders indicates that the presence of this amino acid may not be required for the existence of supercontraction. In this regard, the presence of particular subrepeats--in orb-web and non-orb-web building spiders- adds new clues for the understanding of supercontraction and associated effects. PMID- 20359494 TI - Hyponatremia and predictive rules for prognosis in adult patients with community acquired pneumonia. PMID- 20359491 TI - Sedentary patterns and media availability in European adolescents: The HELENA study. AB - OBJECTIVE: To describe sedentary behaviors in adolescents and to examine the influence of media availability on TV viewing. METHOD: The study assessed 3278 adolescents (1537 males and 1741 females, 12.5-17.5 years) involved in the HELENA study (2007). Adolescents reported hours of TV viewing, computer games, console, internet for study and non-study reasons, and study, as well as availability of TVs, computers and consoles. RESULTS: Time spent in sedentary behaviors was higher during weekends (all p<0.001). Males spent more hours on TV viewing (for > or = 15 years at weekends), playing computer games and console games while females spent more time studying and surfing for non-study reasons. During weekdays, one third of adolescents exceeded the screen time guidelines (>2h/day) based solely on TV viewing, whereas around 60% exceeded it at weekends. Having a TV or a console in the bedroom was associated with higher TV viewing (OR=2.66; 95% CI 2.23-3.18; and OR=1.92; 95% CI 1.61-2.28, respectively) whereas the presence of computer reduced it (OR=0.57; 95% CI 0.48-0.68). CONCLUSION: Adolescents living in Europe are not meeting media recommendations, especially during weekend. The absence of a TV in the adolescents' bedroom might reduce TV viewing. Further studies are needed to confirm or contrast our findings. PMID- 20359495 TI - The impact of a PCR assay for candidemia on antifungal drug prescribing in critical care: an interrupted time series pilot study. AB - SUMMARY OBJECTIVE: To evaluate the feasibility of conducting a definitive study to assess the impact of introducing a rapid PCR-based test for candidemia on antifungal drug prescribing. METHOD: Prospective, single centre, interrupted time series study consisting of three periods of six months' duration. The assay was available during the second period, during which the PCR assay was available for routine use by physicians Monday-Friday with guaranteed 24-h turnaround time. For each period total antifungal drug use, expressed as treatment-days, was recorded and an adjustment was made to exclude estimated use for proven candidemia. Also, during the intervention period, antifungal prescribing decisions for up to 72 h after each PCR result became available were recorded as either concordant or discordant with that result. RESULTS: While overall antifungal use remained relatively stable throughout, after adjustment for candidemia, there was a 38% reduction in use following introduction of the PCR test; however, this was nonsignificant at the 95% level. During the intervention period overall concordance between the PCR result and prescribing decisions was 84%. CONCLUSIONS: The PCR assay for candidemia was requested, prescribing decisions were generally concordant with the results produced and there was an apparent decrease in antifungal prescription, although this was sustained even after withdrawal of the intervention; these findings should be more thoroughly evaluated in a larger trial. PMID- 20359493 TI - Gene-environment interactions: neurodegeneration in non-mammals and mammals. AB - The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both genetic elements and differentiation processes between mammals and non-mammalians. Emerging model organisms, such as the nematode and zebrafish have made it possible to assess the effects of small molecules rapidly, inexpensively, and on a miniaturized scale. By combining the scale and throughput of in vitro screens with the physiological complexity and traditional animal studies, these models are providing relevant information on molecular events in the etiology of neurodegenerative disorders. The utility of these models is largely driven by the functional conservation seen between them and higher organisms, including humans so that knowledge obtained using non-mammalian model systems can often provide a better understanding of equivalent processes, pathways, and mechanisms in man. Understanding the molecular events that trigger neurodegeneration has also greatly relied upon the use of tissue culture models. The purpose of this summary is to provide-state-of the-art review of recent developments of non-mammalian experimental models and their utility in addressing issues pertinent to neurotoxicity (Caenorhabditis elegans and Danio rerio). The synopses by Aschner and Levin summarize how genetic mutants of these species can be used to complement the understanding of molecular and cellular mechanisms associated with neurobehavioral toxicity and neurodegeneration. Next, studies by Sunol and Olopade detail the predictive value of cultures in assessing neurotoxicity. Sunol and colleagues summarize present novel information strategies based on in vitro toxicity assays that are predictive of cellular effects that can be extrapolated to effects on individuals. Olopade and colleagues describe cellular changes caused by sodium metavanadate (SMV) and demonstrate how rat primary astrocyte cultures can be used as predicitive tools to assess the neuroprotective effects of antidotes on vanadium-induced astrogliosis and demyelination. PMID- 20359496 TI - Norovirus outbreak in a cruise ship sailing around the British Isles: investigation and multi-agency management of an international outbreak. AB - OBJECTIVE: Managing an outbreak of gastroenteritis (GI) on board a cruise ship while minimising disruption to passengers' on board and shore visit activities is difficult. For this reason it is important to understand the complex patterns of transmission in a closed community. We describe the epidemiological investigation of an outbreak of norovirus during an international cruise. METHODS: A retrospective cohort study was conducted using information from lists routinely maintained by the travel company, including the passenger manifest, and organised coach tour lists. Information on air-conditioning (AC) systems was used to assess the possible sources of exposures. FINDINGS: Of the 1194 passengers 191 (16%) and 5 crew (<1%) became ill with GI symptoms. The attack rate was higher amongst passengers whose cabin was on the main deck (RR 3.41, 95% CI 1.47-7.94) that houses both passengers' cabins and leisure facilities including shops. Passengers who went on one of the organised coach tours where there were symptomatic passengers were at an increased risk of infection (RR 2.14, CI 1.51-3.03). Analysis of the 56 AC sections on the ship and did not detect an association with infection. CONCLUSIONS: Patterns of transmission of norovirus on a cruise ship are complex. Our study suggests infections are more likely among those passengers staying in areas of the ship that are highly transited or used for communal activities and more difficult to clean. Emphasis on the importance of early reporting of symptoms can help minimise transmission. Internationally agreed guidelines on the management of outbreaks on cruise ships are needed. PMID- 20359497 TI - A successfully treated case of peritonitis due to Fusarium dimerum. AB - SUMMARY: Fungal peritonitis is a rare but serious complication of continuous ambulatory peritoneal dialysis (CAPD). We report the first known case of CAPD peritonitis due to Fusarum dimerum successfully treated with antifungals and catheter removal. PMID- 20359498 TI - Invasive group A streptococcal infection in pregnancy. AB - We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics and intravenous immunoglobulin may improve outcome of pregnant women suffering from flu-like symptoms, shock and strong uterine contractions suggestive of placental abruption. PMID- 20359499 TI - A rotarod test for evaluation of motor skill learning. AB - The rotarod test is widely used to evaluate the motor coordination of rodents, and is especially sensitive in detecting cerebellar dysfunction. However, mice with striatal dopamine depletion show only mild or no motor deficit on the typical accelerating rotarod. This suggests that dopamine-depleted mice are useful as animal models for non-motor symptoms, because the influence of motor deficit is minimum and easy to discriminate from cognitive aspects of the behavioral change. The typical accelerating rotarod test is designed to evaluate maximal motor performance and is not optimized to detect motor skill learning. In an attempt to make the test more selective to motor skill learning rather than maximal gait performance, we modified the rotarod test by using a slowly rotating large drum to obtain a steep learning curve. Furthermore, administration of nomifensine, a dopamine uptake inhibitor, improved the learning. On the other hand, apomorphine, an agonist of dopamine autoreceptor, a dopaminergic toxin, 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impaired the learning. These pharmacological profiles fit the involvement of the so-called phasic dopamine neurotransmission. Using our modified procedure, we found impaired learning of Parkin-deficit mice, which has not been detected in typical accelerating rotarod. The modified rotarod test would be useful for evaluation of dopamine involvement in the acquisition of motor skill learning. PMID- 20359501 TI - Environmental enrichment and chronic restraint stress in ICR mice: effects on prepulse inhibition of startle and Y-maze spatial recognition memory. AB - In most studies regarding the improving or therapeutical effects induced by enriched environment (EE), EE was performed after the stress treatment or in patients with certain diseases. In the current study, the effects of chronic restraint stress (6h/day) in mice living in an enriched environment or standard environment (SE) were tested. Mice were randomly divided into 4 groups: non stressed or stressed mice housed in SE or EE conditions (SE, stress+SE, EE, stress+EE). Prepulse inhibition (PPI) of startle was tested after the 2 weeks or 4 weeks stress and/or EE treatment and 1 or 2 weeks withdrawal from the 4 weeks treatment. After the 4 weeks treatment, spatial recognition memory in Y-maze was also tested. The results showed that EE increased PPI in stressed and non stressed mice after 2 weeks treatment. No effect of EE on PPI was found after the 4 weeks treatment. 4 weeks chronic restraint stress increased PPI in mice housed in standard but not EE conditions. Stressed mice showed deficits on the 1h delay version of the Y-maze which could be prevented by living in an enriched environment. Our results indicated that living in an enriched environment reversed the impairing effects of chronic restraint stress on spatial recognition memory. However, EE did not change the effects of stress on PPI. PMID- 20359500 TI - Population decoding of motor cortical activity using a generalized linear model with hidden states. AB - Generalized linear models (GLMs) have been developed for modeling and decoding population neuronal spiking activity in the motor cortex. These models provide reasonable characterizations between neural activity and motor behavior. However, they lack a description of movement-related terms which are not observed directly in these experiments, such as muscular activation, the subject's level of attention, and other internal or external states. Here we propose to include a multi-dimensional hidden state to address these states in a GLM framework where the spike count at each time is described as a function of the hand state (position, velocity, and acceleration), truncated spike history, and the hidden state. The model can be identified by an Expectation-Maximization algorithm. We tested this new method in two datasets where spikes were simultaneously recorded using a multi-electrode array in the primary motor cortex of two monkeys. It was found that this method significantly improves the model-fitting over the classical GLM, for hidden dimensions varying from 1 to 4. This method also provides more accurate decoding of hand state (reducing the mean square error by up to 29% in some cases), while retaining real-time computational efficiency. These improvements on representation and decoding over the classical GLM model suggest that this new approach could contribute as a useful tool to motor cortical decoding and prosthetic applications. PMID- 20359502 TI - Attention to visual, but not tactile, properties of a stimulus results in activation of FOS protein in the visual thalamic reticular nucleus of rats. AB - Previous reports have suggested that the modality-specific sectors of the thalamic reticular nucleus (TRN) may become selectively activated as a result of attention being drawn to their respective sensory modalities. Here we used a task that required the discrimination of digging bowls on the basis of their visual (the colour of the bowl) or tactile (the external texture of the bowl) characteristics. We trained rats to perform both modality discriminations, ensuring the equity of exposure to both visual and tactile aspects of the stimuli. On the test day, animals had to perform only one of the modality discriminations for a 1-h period prior to being transcardially perfused and their brains removed and processed for Fos immunocytochemistry. We found that animals that performed the visual discrimination prior to sacrifice demonstrated a selective activation of cells in the visual TRN. On the other hand, animals that had performed the tactile discrimination, despite encountering the same stimuli and having received equal visual stimulation as the animals performing the visual discrimination, did not have activation of the visual TRN. This evidence suggests that activation of visual TRN is a function of visual selective attention, and not merely visual stimulation. Surprisingly, the same was not true for somatic TRN, which was not labeled in any animals. It is possible that this lack of a double dissociation is the result of modality-specific differences in the attentional demands of the two discrimination tasks. PMID- 20359503 TI - Changes in food intake and anxiety-like behaviors after clonidine injected into the median raphe nucleus. AB - Serotonergic neurons in the median raphe nucleus (MnR) are stimulated by alpha(1) adrenergic agonists and inhibited by alpha(2) agonists. This study investigated the participation of MnR alpha(2)-adrenergic receptors in the control of anxiety like behavior and feeding as an attempt to establish a functional association between these behaviors. The alpha(2)-adrenergic agonist clonidine (CLON) was injected into the MnR (0, 0.2, 2, 6, 20nmol), into the pontine nucleus (Pn) or into the mesencephalic reticular formation (mRt) (0.2, 20nmol) of free-feeding rats. The animals were exposed to the elevated plus-maze to evaluate spatial temporal and ethological variables. Subsequently, the ingestive and non-ingestive behaviors were recorded during 30min and the quantity of food and water consumed were measured. The lowest dose of CLON injected into the MnR decreased the total risk assessment (TRA) frequency, an ethological parameter of anxiolytic-like effect, but did not change feeding behavior. The highest dose of CLON injected into the MnR increased the TRA frequency, an anxiogenic-like effect. Similar result was observed after CLON injected into the Pn and mRt at the highest dose. In addition, clonidine at the highest dose caused hyperphagy accompanied by a reduction in the latency to start eating and an increase in feeding frequency when injected into the MnR but not in the Pn or mRt. These data indicate that MnR alpha(2)-adrenergic receptors participate in the control of anxiety-like and feeding behaviors, probably decreasing the facilitatory influence on MnR serotonergic neurons. The present results suggest that these behaviors involve independent neural pathways. PMID- 20359504 TI - The moonlighting function of pyruvate carboxylase resides in the non-catalytic end of the TIM barrel. AB - Pyruvate carboxylase is a highly conserved enzyme that functions in replenishing the tricarboxylic acid cycle with oxaloacetate. In the yeast Hansenulapolymorpha, the pyruvate carboxylase protein is also required for import and assembly of the peroxisomal enzyme alcohol oxidase. This additional role, which is unrelated to the enzyme activity, represents an example of a special form of multifunctionality called moonlighting. We have performed a detailed site directed mutagenesis approach to elucidate which region(s) of H. polymorpha pyruvate carboxylase are involved in its second function. This resulted in the identification of three amino acids that are essential for the moonlighting function. Mutating these residues in a single mutant protein fully inactivated the moonlighting function, but not the enzyme activity of pyruvate carboxylase because the strain was prototrophic. A 3D homology model revealed that all three residues are positioned at the side of a TIM barrel where the N-terminal ends of the beta-strands are located. This is a novel observation as the TIM barrel proteins invariably are enzymes and have their catalytic side at the C-terminal end of the beta-sheets. Our finding implies that a TIM barrel fold can also fulfill a non-enzymatic function and that this function can reside at the N terminal end of the barrel. PMID- 20359505 TI - Interaction between the motor protein prestin and the transporter protein VAPA. AB - Prestin is the motor protein responsible for cochlear outer hair cell (OHC) somatic electromotility. Eliminating this abundant basolateral membrane protein not only causes loss of frequency selectivity and hearing sensitivity, but also leads to OHC death. A membrane-based yeast two-hybrid approach was used to screen an OHC-enriched cDNA (complementary Deoxyribonucleic Acid) library in order to identify prestin-associated proteins. Several proteins were recognized as potential prestin partners, including vesicle-associated membrane protein associated protein A (VAPA or VAP-33). VAPA is an integral membrane protein that plays an important role in membrane trafficking, endoplasmic reticulum homeostasis, and the stress-signaling system. The connection between VAPA and prestin was confirmed through co-immunoprecipitation experiments. This new finding prompted the investigation of the interaction between VAPA and prestin in outer hair cells. By comparing VAPA expression between wild-type OHCs and OHCs derived from prestin-knockout mice, we found that VAPA is expressed in OHCs and the quantity of VAPA expressed is related to the presence of prestin. In other words, less VAPA protein is found in OHCs lacking prestin. Thus, prestin appears to modify the expression of VAPA protein in OHCs. Intriguingly, more prestin protein appears at the plasma membrane when VAPA is co-expressed with prestin. These data suggest that VAPA could be involved in prestin's transportation inside OHCs and may facilitate the targeting of this abundant OHC protein to the plasma membrane. PMID- 20359506 TI - Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes. AB - PGC-1alpha is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1alpha expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1alpha participates in the regulation of muscle mass. PGC-1alpha gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1alpha in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1alpha expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21days, the levels of PGC-1alpha protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1alpha transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1alpha regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1alpha expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 mRNAs were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1alpha were also decreased in muscles of CnAalpha-/- and CnAbeta-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1alpha expression. These findings demonstrate that Cn activity is a major determinant of PGC-1alpha expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass. PMID- 20359507 TI - JNK inhibition arrests cotranslational degradation. AB - Adhesion to fibronectin stimulates protein synthesis (translation) of fibroblasts. Protein synthesis stimulation is dependent from the activation of beta(1)-integrin. beta(1)-Integrin elicits a PI3K cascade that modulates eIF4F (eukaryotic initiation factor 4F) complex formation. In the attempt to further dissect elements of the PI3K cascade that might be responsible for fibronectin stimulated translation, we used pharmacological inhibitors of known kinases. We found that JNK inhibition, by SP600125 treatment, increased (35)S-methionine incorporation. Paradoxically, the increase in methionine incorporation was associated to a reduction of initiation of translation. These data imply that, during the adhesion of fibroblasts to fibronectin, conspicuous protein degradation occurs. Indeed, we found that inhibition of the proteasome by MG132 also increased methionine incorporation. Cotranslational degradation depended on PI3K activation. In spite of this, serum promoted translation, but not cotranslational degradation. The crosstalk between translation and degradation was further analyzed by studying the phosphorylation of initiation factors. Briefly, inhibition of JNK leads to eIF2alpha phosphorylation, which may account for the decrease in initiation of translation. In conclusion, beta(1)-integrin activated translation causes the synthesis of short-lived proteins, whose degradation is controlled by the JNK pathway. We hypothesize that JNK is a general regulator of cotranslational degradation. PMID- 20359508 TI - A novel selective growth medium-PCR assay to isolate and detect Sphingomonas in environmental samples. AB - Sphingomonas species can be found ubiquitously in the environment and can be frequently found in surface biofilms. Some Sphingomonas strains are well known for metabolizing complex organic pollutants but some are opportunistic human pathogens. Despite the importance of the Sphingomonas species, a reliable system to isolate this group of bacteria from the environment has not been developed. In this study, a combined streptomycin-piperacillin selective growth medium/polymerase chain reaction (PCR) detection approach is developed to isolate and identify the Sphingomonas bacteria. A total of 72 known Sphingomonas strains (including 21 different Sphingomonas species type strains) and 14 non Sphingomonas species were tested using a new Sphingomonas-specific growth medium containing 100 and 50 microg/ml streptomycin and piperacillin, respectively. All the Sphingomonas strains showed positive growth on the selective medium and no growth was shown by the non-Sphingomonas species. In addition, two sets of PCR primers targeting the serine palmitoyltransferase gene (spt), a crucial sphingolipid biosynthesis gene, were developed. With the exception of the Sphingomonas subarctica type strain, 71 of the 72 known Sphingomonas samples were amplified positively by either one or both of the spt-specific primers. None of the non-Sphingomonas bacteria were amplified by the spt primers. To verify the effectiveness of this novel approach for use in environmental screening applications the Sphingomonas selective medium was used to isolate 165 potential Sphingomonas isolates, including 101 yellow, 4 orange and 58 unpigmented isolates, from the influent water and biofilm samples of a pulp and paper mill in Northwestern Ontario. Screening of these isolates with the two Sphingomonas spt PCR primer sets showed that 98% of the yellow isolates and 100% of the orange isolates were positive to the spt-PCR test. None of the unpigmented isolates was positive to the spt-PCR assay. The 16S rDNA of 17% of the spt+ve and -ve isolates were sequenced and analyzed. All of the yellow and orange pigmented isolates were Sphingomonas while none of the unpigmented isolates were Sphingomonas. REP-PCR was performed on 79 Sphingomonas samples randomly selected from the paper mill and hospital isolates and showed that a diverse group of Sphingomonas can be grown or isolated by our Sphingomonas selective growth medium. Therefore, by using the streptomycin-piperacillin selective growth medium in combination with the colour pigmentation and the positive spt-PCR reactions of the isolates, a diverse population of Sphingomonas strains can be isolated and identified from complex microbial communities with high accuracy. PMID- 20359509 TI - Introduction of stearoyl moieties into a biocompatible cationic polyaspartamide derivative, PAsp(DET), with endosomal escaping function for enhanced siRNA mediated gene knockdown. AB - Applications of siRNA for cancer therapy have been spotlighted in recent years, but the rational design of efficient siRNA delivery carriers is still controversial, especially because of possible toxicity of the carrier components. Previously, a cationic polyaspartamide derivative, poly{N-[N-(2-aminoethyl)-2 aminoethyl]aspartamide} (PAsp(DET)), was reported to exert high transfection efficacy for plasmid DNA with negligible cytotoxicity. However, its direct application for siRNA delivery was fairly limited due to the unstable polymer/siRNA complex formation. In this study, to overcome such instability, stearic acid as a hydrophobic moiety was conjugated to the side chain of PAsp(DET) with various substitution degrees. The stearoyl introduction contributed not only to siRNA complex formation with higher association numbers but also to complex stabilization. The obtained stearoyl PAsp(DET)/siRNA complex significantly accomplished more efficient endogenous gene (BCL-2 and VEGF) knockdown in vitro against the human pancreatic adenocarcinoma (Panc-1) cells than did the unmodified PAsp(DET) complex and commercially available reagents, probably due to the facilitated cellular internalization. This finding suggests that the hydrophobic PAsp(DET)-mediated siRNA delivery is a promising platform for in vivo siRNA delivery. PMID- 20359510 TI - Fractional laser as a tool to enhance the skin permeation of 5-aminolevulinic acid with minimal skin disruption: a comparison with conventional erbium:YAG laser. AB - The aim of this study was to examine the in vitro skin delivery and in vivo protoporphyrin IX (PpIX) accumulation of topically applied 5-aminolevulinic acid (ALA) enhanced by a fractional laser pretreatment. This was achieved by applying an array of microscopic treatment zones (MTZ) to the skin by ablation of superficial stratum corneum in a determined area. Re-epithelialization determined by transepidermal water loss was completed within 1 day after fractional laser irradiation. The conventional laser used in comparison showed more severe skin disruption and a greater recovery duration of 2 days. The in vitro ALA permeation was measured using a Franz cell apparatus, with nude mouse skin and porcine skin as the permeation barriers. The efficacy of the enhancement was determined as a function of various laser fluences (2 and 3 J/cm(2)) and number of passes (1-6 passes). The flux of ALA via laser-treated nude mouse skin was 27-124-fold higher than that across intact skin. A 3-260-fold increase in ALA flux was detected by using the porcine skin as the permeation barrier. The skin permeation was also investigated in a model of hyperproliferative skin obtained by repeated tape stripping. The results showed that the hyperproliferative skin was more permeable to ALA in comparison to the normal skin. The in vivo localization of PpIX in nude mouse skin was imaged using confocal laser scanning microscopy. As expected, an intense red fluorescence was observed in the lower epidermis and upper dermis after fractional laser irradiation. The penetration depth was also increased by the laser. The safety and efficacy of enhancing ALA permeation were demonstrated by using the fractional laser at low fluences. PMID- 20359511 TI - Silver nano - a trove for retinal therapies. AB - Pathological retinal angiogenesis (neovascularization) is one of the most feared complications among retinal diseases, leading to visual impairment and irreversible blindness. Recent findings made by us on therapeutic applications of biologically synthesized silver nanoparticles (AgNPs) against VEGF induced retinal endothelial cells, elucidates the effectual inhibitory activities of AgNPs over the downstream signaling pathways (Src and AKT/PI3K) leading to retinal angiogenesis. The current review focuses on the imperative role of VEGF induced angiogenesis in the development of retinal neovascularization and despite the fact that several VEGF targeting ocular drugs are available; the review examines the need for a cost economic alternative, thereby suggesting the role of AgNPs as an emerging economic ocular drug for retinal therapies. The current technologies available for the development of targeted and controlled release of drugs is being discussed and a model has been proposed for the amenable targeting mechanism, by which Poly gamma glutamic acid (PGA) capsulated AgNPs conjugated to cyclic RGD peptides carry out a sustained controlled release specifically targeting the neovascularization cells and induce apoptosis unaffecting the normal retinal cells. These constructs consequently affirm the futuristic application of silver nanoparticles as a boon to ocular therapies. PMID- 20359512 TI - Electrochemically controlled drug delivery based on intrinsically conducting polymers. AB - This paper reviews the application of intrinsically conducting polymers (ICPs) in drug delivery. ICPs are organic polymers with electrical, magnetic and optical properties usually associated with metals, whilst retaining the advantageous mechanical properties and ease of processing usually associated with polymers. Due to the inherent properties of these unique materials, electrical stimulation can be used to alter the redox state of ICPs, which in turn can modify the release rate of drug. The controlled release of drugs from ICPs has been reported in the literature since the 1980s. Following continued development, clinical applications of ICP-based drug delivery systems (DDS) have been reported recently. The next generation of controlled release technologies could utilise the biosensing properties of ICPs combined with their drug delivering abilities to develop an intelligent drug delivery system from a single material where the release rate of drug self adjusts in response to a sensed change in local body environment. This article provides an overview of ICP synthesis and properties relevant to their use as DDS, including biodegradability and biocompatibility, followed by literature on ICP-based DDS examining different methods of drug incorporation and release. The pharmaceutical applications of these systems have also been discussed. It is concluded that ICPs hold great promise in drug delivering implants where the dose can be adjusted through application of external stimulus, thus optimising benefit to side effect ratio while simultaneously ensuring patient adherence. PMID- 20359513 TI - Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death. AB - Partial inactivation and transient depletion of monocytes/macrophages by liposomal bisphosphonates (LIP-BPs) is widely experimented in various inflammatory disorders including restenosis. Previous studies on activation of cytokines by LIP-BPs are limited to certain cell lines. Moreover, the correlation between in vitro and in vivo studies and complement (C) activation has not been reported. We report here a comprehensive study on the bioactivity of LIP-BPs on various cells' internalization and proliferation, mechanism of cell death, cytokines (in vitro and in vivo) and C activation (in the rat, rabbit and pig). The role of the following parameters has been determined i) drug type (clodronate/alendronate); ii) vesicles size (60-800nm); iii) charge (neutral/negative/ positive); and iv) cell culture type (various cell lines and primary cultures). It was found that monocyte/macrophage inhibition and cytokine activation depend on the cell type, with a limited correlation to the bioactivity obtained in the rat and rabbit models of restenosis. Negatively charged liposomes (85+/-20nm) effectively depleted rabbit's monocytes (67% depletion), with a minor activation of cytokines and no C activation. It is concluded that cell culture studies are insufficient for assessing cytokine activation, and that by controlling LIP-BP properties (size, charge and drug type) optimal bioactivity could be achieved. PMID- 20359514 TI - Asthma: Chronopharmacotherapy and the molecular clock. AB - Bronchial asthma is characterized by chronic airways inflammation and reversible airflow limitation. In patients with asthma, symptoms generally worsen during the early hours of the morning, and pulmonary function often deteriorates at the same time, suggesting a role for chronopharmacotherapy. Several drugs for asthma have been developed based on chronopharmacology. Most medications employed for the chronotherapy of asthma are administered once at night with the goal of preventing chronic airway inflammation or development of airflow limitation. In addition to bronchodilators, the inhaled glucocorticosteroid ciclesonide is now available with once-daily dosing, which also improves patients' compliance. Numerous investigations have demonstrated the usefulness of chronotherapy for asthma, especially for patients with nocturnal asthma. This review focuses on chronotherapy of asthma, and also provides a molecular biological explanation for the influence of asthma medications on the clock genes. PMID- 20359515 TI - Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells. AB - Tau is a main component of the aberrant paired helical filaments (PHF) found in Alzheimer's disease (AD). It has also been reported to enhance oxidative stress, which is a major factor in the pathogenesis of neurodegenerative diseases. However, protective functions of Tau have recently been reported, including antagonizing apoptosis, in addition to its role in stabilizing microtubules. In this study, the interaction between Tau and triose phosphate isomerase (TPI) in a normal, nondisease state as well as in a neurodegeneration state was examined and demonstrated for the first time. More importantly, we also showed that Tau protects TPI against oxidative damage. An oxidative stress-induced decrease in the activity of TPI was attenuated in Tau-overexpressing cells, indicating that Tau protects TPI against oxidative damage. By contrast, the activity of TPI was decreased in Tau-transgenic (Tg) mice compared to non-Tg (NTg) mice even though protein levels were not changed in both groups. Some TPIs were found on the PHF in Tg mice, which explains the decrease in the activity of TPI. Taken together, we concluded that while Tau binds and protects TPI in normal cells, and conversely, the formation of PHF induced by Tau phosphorylation trap some TPI and trigger the functional loss of TPI in the development of neurodegenerative diseases. Our results provide new insights into understanding the in-depth involvement of Tau in the development of neurodegenerative disorders. PMID- 20359516 TI - CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese. AB - CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) -336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)-coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico pathologic outcomes in 824 serologic confirmed SARS patients showed that the 336AG/GG genotype SARS patients was associated with lower standardized lactate dehydrogenase (LDH) levels compared with the -336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 -336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating. PMID- 20359517 TI - Gene expression profiles of human promyelocytic leukemia cell lines exposed to volatile organic compounds. AB - Benzene, toluene, o-xylene, ethylbenzene, trichloroethylene and dichloromethane are the most widely used volatile organic compounds (VOCs), and their toxic mechanisms are still undefined. This study analyzed the genome-wide expression profiles of human promyelocytic leukemia HL-60 cells exposed to VOCs using a 35-K whole human genome oligonucleotide microarray to ascertain potential biomarkers. Genes with a significantly increased expression levels (over 1.5-fold and p values <0.05) with six VOCs were then classified with gene ontology and KEGG pathway annotation. At IC(20) doses identified genes were functionally categorized as being involved in cytokine-cytokine receptor interactions and the toll-like receptor signaling pathway, whereas exposure at IC(50) doses identified genes associated with the p53 signaling pathway, apoptosis, and natural killer cell-mediated cytotoxicity pathway. Functionally important immune response- and apoptosis-related genes were further validated by real-time RT-PCR. The results showed that IFIT1, IFIT2, IFIT3, USP18, INFGR2, PMAIP1, GADD45A, NFKBIA, TNFAIP3, and BIRC3 genes altered their expression profiles in a dose-dependent manner. Similar expressions profiles were also found in human erythromyeloblastoid leukemia K562 cells and in human leukemic monocyte lymphoma U937 cells. In conclusion, both gene expression profiles and gene ontology analysis have elucidated potential gene-based biomarkers and provided insights into the mechanism underlying the response of human leukemia cell lines to VOC exposure. PMID- 20359518 TI - Variations in human DEJ scallop size with tooth type. AB - OBJECTIVE: Recent literature suggests that the scalloped structure of the dentino enamel junction (DEJ) is critical for DEJ stability. Aim of our study was to see if there are differences in scallop size and shape with tooth type. METHODS: Enamel of extracted permanent human teeth was demineralised using EDTA. After fixation and dehydration the scallops of the DEJ were investigated in a scanning electron microscope. Scallop area and shape (circularity) were measured for molars, premolars, canines and incisors. RESULTS: Scallop area showed main effects for tooth type and specimen, while, due to high variability in third molars, there was also an interaction effect (repeated measures two-way ANOVA, p<0.05). Differences between tooth types were statistically significant, suggesting that posterior teeth showed larger scallops compared to anterior teeth. Differences in shape (circularity) were not statistically significant. CONCLUSION: Our results suggest that teeth which are subject to higher masticatory loads (posterior teeth) show larger and more pronounced scallops. These findings might be of interest for improving other interfaces joining dissimilar materials. PMID- 20359519 TI - Heterologous expression of non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Triticum aestivum and Arabidopsis thaliana. AB - Non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (np-Ga3PDHase) plays a key metabolic role in higher plants. Purification to homogeneity of enzymes found in relatively low abundance in plants represents a major technical challenge that can be solved by molecular gene cloning and heterologous expression. To apply this strategy to np-Ga3PDHase we performed the cloning of the gapN gene from Arabidopsis thaliana and Triticum aestivum, followed by the heterologous expression in Escherichia coli by two different strategies. Soluble expression of the Arabidopsis enzyme in the pET32c+ vector required a chaperone co-expression system (pGro7). The system using E. coli BL21-CodonPlus cells and the pRSETB vector was successful for expression of a soluble His(6)-taged recombinant wheat enzyme producing 2.5 mg of electrophoretically pure protein per liter of cell culture after a single chromatographic purification step. Both systems were effective for the expression of functional plant np-Ga3PDHases, however the expression of the Arabidopsis enzyme in pRSETB was affordable but not as optimal as for the wheat protein. This would be associated with a different codon usage preference between this specific plant and E. coli. Considering the relevant role played by np-Ga3PDHase in plant metabolism, it is experimentally valuable the development of a procedure to obtain adequate amounts of highly purified enzyme, which envisages the viability to perform studies of structure-to function relationships to better understand the enzyme kinetics and regulation, as well as carbon and energy metabolism in higher plants. PMID- 20359520 TI - Small conductance calcium-activated potassium channels: from structure to function. AB - The cloning of K(Ca)2 channels revealed three subtypes, with each displaying distinct but partially overlapping expression distributions in the mammalian CNS and periphery. Activation of K(Ca)2 channels leads to membrane hyperpolarization and inhibition of action potential firing. Block of K(Ca)2 channels has been suggested as a novel target for cognitive enhancement, depression, myotonic muscular dystrophy and heart arrhythmias. It is clear however, that blockers selective for individual K(Ca)2 channel subtypes would be required to be therapeutically useful. K(Ca)2 channel current is blocked by apamin, with the bee venom toxin being unusual in displaying some selectivity between K(Ca)2 channel subtypes. This suboptimal selectivity is not sufficient to be therapeutically useful and the toxin has been shown in vivo to have a very narrow therapeutic window. Mutational and molecular modelling studies of the K(Ca)2 channels are beginning to determine how selective block might be achieved. Mutagenesis has indicated the importance of the outer pore region and the extracellular loop between transmembrane domains S3 and S4 for block of K(Ca)2 current by apamin. Mapping the sequence of transmembrane domains S5, pore helix and S6 onto the crystal structures of KcsA, MthK and Kv1.2 has provided an approximation of the pore structure. This approach has allowed structural modelling of the interactions between toxins and channel, demonstrating that the toxins that show little discrimination between K(Ca)2 channel subtypes interact with the outer pore and around the K(+) selectivity filter. We present the structural modelling of the interaction of apamin and K(Ca)2.2, which is superimposed onto the crystal structure of Kv1.2. This has shown that apamin interacts only with the outer pore and does not come into contact with channel's selectivity filter. It is clear that by comparing how different toxins interact with each K(Ca)2 channel subtype, a detailed picture will be generated that will aid the development of more specific K(Ca)2 channel blockers. PMID- 20359521 TI - Testosterone responses to competition: The opponent's psychological state makes it challenging. AB - Testosterone (T) increases after competition have typically been attributed to winning, yet there is also evidence that being victorious is not in itself sufficient to provoke a T response. Instead, it has been proposed that T responses are moderated by psychological processes. Here, we investigated whether the opponent's psychological state affected hormonal changes in men competing face to face on a rigged computer task. The results show that, irrespective of outcome, the competition led to increases in heart rate and T levels. We found that the T levels of the participants increased more when their opponents had high self-efficacy and that T levels were not influenced by participants' own psychological state. Furthermore, the T levels of losers, but not winners, increased more when their opponent judged the competition to have low importance. The findings from this study are consistent with the challenge hypothesis. Both winners and losers were being challenged to compete for social status; therefore their T responses did not differ. In addition, the psychological state of the opponent makes a competition challenging and subsequently triggers T responses. PMID- 20359522 TI - Ubiquitination and SUMOylation of annexin A1 and helicase activity. AB - BACKGROUND: While annexin A1 in nuclei is proposed to be involved in cell transformation, its functions remain poorly understood. Since annexin A1 has the consensus motif, 160LKRD, for SUMOylation as well as Ks, acceptors for ubiquitination that regulates localization and functions of proteins, we investigated SUMOylation and ubiquitination of annexin A1. METHODS: SUMOylation and ubiquitination of bovine annexin A1 were biochemically tested in vitro by purified proteins, and were confirmed by cell experiments with L5178 lymphoma cells. Effects of the modifications on DNA helicase activity were measured by ssDNA binding activity and by dsDNA unwinding activity. RESULTS: SUMOylation of annexin A1 was catalyzed by Ubc9, while its ubiquitination was by Rad6-Rad 18. Ubiquitinated annexin A1 had higher affinity for damaged DNA, and promoted in vitro translesion DNA synthesis by Pol beta. In mouse lymphoma L5178Y tk(+/-) cells, levels of SUMOylated annexin A1 decreased by DNA damaging agents, MMS or As3, whereas those of ubiquitinated annexin A1 increased under the same conditions. CONCLUSION: These observations suggest but do not necessarily prove that ubiquitinated annexin A1 in nuclei may be involved in DNA damage response, while SUMOylated annexin A1 functions in proliferation-differentiation. SIGNIFICANCE: Ubiquitination of annexin A1 may play an important role in mutagenesis, an initial step of cell transformation. PMID- 20359523 TI - Activation of antioxidant defenses in response to freezing in freeze-tolerant painted turtle hatchlings. AB - BACKGROUND: Hatchlings of the painted turtle, Chrysemys picta marginata can endure long-term freezing of their extracellular body fluids. We hypothesized that freezing survival would include adaptive up-regulation of antioxidant defenses to deal with ischemia-reperfusion injuries associated with the freeze thaw cycle. A number of antioxidant enzymes are under the control of the NF-E2 related factor 2 (Nrf2) transcription factor including members of the glutathione S-transferase (GST) and aldo-keto reductase (AKR) families. METHODS: RT-PCR and Western immunoblotting were used to measure changes in transcript and protein levels in response to 5-h freezing exposure of hatchlings. RESULTS: Transcript levels of Nrf2 increased in turtle brain, liver, and muscle by 1.5- to 2-fold, and protein levels increased in the brain and muscle by 1.6- to 2.3-fold in response to freezing. GSTs responded strongly to freezing in turtle brain with amounts of GSTP1, M1, K1, and A3 elevated by 1.5- to 2.4-fold. GSTM3 and T1 rose by 1.8- to 2.3-fold in gut, whereas reduced levels of GSTP1, M1, M3, and K1 were found in livers of frozen animals. Levels of the AKR1B4 isozyme rose 2.1-fold during freezing in brain. CONCLUSIONS: Freezing triggered tissue-specific changes in the antioxidant defenses in C.pictamarginata organs. GENERAL SIGNIFICANCE: These data indicate that activation of an antioxidant response is an important aspect of natural freeze tolerance in turtles. PMID- 20359524 TI - Nocistatin excites rostral agranular insular cortex-periaqueductal gray projection neurons by enhancing transient receptor potential cation conductance via G(alphaq/11)-PLC-protein kinase C pathway. AB - Rostral agranular insular cortex (RAIC) projects to periaqueductal gray (PAG) and inhibits spinal nociceptive transmission by activating PAG-rostral ventromedial medulla (RVM) descending antinociceptive circuitry. Despite being generated from the same precursor prepronociceptin, nocistatin (NST) and nociceptin/orphanin FQ (N/OFQ) produce supraspinal analgesic and hyperalgesic effects, respectively. Prepronociceptin is highly expressed in the RAIC. In the present study, we hypothesized that NST and N/OFQ modulate spinal pain transmission by regulating the activity of RAIC neurons projecting to ventrolateral PAG (RAIC-PAG). This hypothesis was tested by investigating electrophysiological effects of N/OFQ and NST on RAIC-PAG projection neurons in brain slice. Retrogradely labeled RAIC-PAG projection neurons are layer V pyramidal cells and express mRNA of vesicular glutamate transporter subtype 1, a marker for glutamatergic neurons. N/OFQ hyperpolarized 25% of RAIC-PAG pyramidal neurons by enhancing inwardly rectifying potassium conductance via pertussis toxin-sensitive G(alphai/o). In contrast, NST depolarized 33% of RAIC-PAG glutamatergic neurons by causing the opening of canonical transient receptor potential (TRPC) cation channels through G(alphaq/11)-phospholipase C-protein kinase C pathway. There were two separate populations of RAIC-PAG pyramidal neurons, one responding to NST and the other one to N/OFQ. Our results suggest that G(alphaq/11)-coupled NST receptor mediates NST excitation of RAIC-PAG glutamatergic neurons, which is expected to cause the supraspinal analgesia by enhancing the activity of RAIC-PAG-RVM antinociceptive pathway. Opposite effects of NST and N/OFQ on supraspinal pain regulation are likely to result from their opposing effects on RAIC-PAG pyramidal neurons. PMID- 20359525 TI - The primary role of glutathione against nuclear DNA damage of striatum induced by permethrin in rats. AB - Pyrethroids are one of the most widely used class of insecticides and their toxicity is dominated by pharmacological actions upon the CNS. This study reports as the subchronic treatment (60 days) with permethrin (PERM) (1/10 of LD(50)) induced nuclear DNA damage in rat striatum cells. Comet assay outcomes showed that PERM produced single- and double-strand breaks in striatum cells, the DNA damage was not related to oxidation at pyrimidine and purine bases. Vitamin E (280 mg/kg body weight/day) and vitamin E+coenzyme Q(10) (10 mg/kg/3 ml) supplementation could protect PERM treated rats against nuclear DNA damage. With the aim to evaluate the cause of nuclear DNA damage observed in striatum of rat treated with PERM, in vitro studies on striatum submitochondrial particles (SMPs) and on striatum cells treated with 10 muM PERM alone or plus 16 or 32 nM GSH were performed. SMPs incubated with PERM showed a decrease in superoxide anion release from the electron transport chain by inhibition of mitochondrial complex I. The effect could be related to the decrease of membrane fluidity measured in the hydrophilic-hydrophobic region of the mitochondrial membrane. This result discarded the involvement of the mitochondrial reactive oxygen species in the nuclear DNA damage. On the contrary, GSH played a crucial role on striatum since it was able to protect the cells against nuclear DNA damage induced by PERM. In conclusion our outcomes suggested that nuclear DNA damage of striatum cells was directly related to GSH depletion due to PERM insecticide. PMID- 20359527 TI - Transdermal permeation of geniposide in the herbal complex liniment in vivo and in vitro. AB - Zhongtong Caji, a kind of liniment, is a traditional Chinese medicinal formula that is widely used for clinical treatment of inflammation and sprains. In this study, the principal effective compound of this formula, geniposide, was used as a criterion to represent the transdermal permeability of the whole formula. A passive diffusion of Zhongtong Caji through the stratum corneum was discovered by an in vitro experiment. The dosage-content relationship detected in subcutaneous tissue after in vivo drug administration was further evidence of its permeation. Blood analysis after different dosages showed that the geniposide could be absorbed and accumulated by subcutaneous tissue within 1h after drug administration, and it would be eliminated by blood circulation 1h after drug treatment. PMID- 20359526 TI - Spinal mediators that may contribute selectively to antinociceptive tolerance but not other effects of morphine as revealed by deletion of GluR5. AB - Several groups maintain that morphine tolerance and dependence correlate with increased activity of protein kinases ERK1/2 and P38 MAPK and PKC as well as elevated levels of the neuropeptides dynorphin (DYN), substance P (sP), and calcitonin gene-related peptide (CGRP) in spinal cord dorsal horn (SCDH). They demonstrate that tolerance and dependence can be prevented, and sometimes reversed, by constitutive genetic deletion or pharmacological inhibition of these factors. Recently, we showed that mice with a constitutive deletion of the GluR5 subunit of kainate receptors (GluR5 KO) are not different from wild type (WT) littermates with respect to baseline nociceptive thresholds as well as acute morphine antinociception, morphine physical dependence and conditioned place preference. However, unlike WT, GluR5 KO mice do not develop antinociceptive tolerance following systemic morphine administration. In this report, we examined levels of these mediators in SCDH of WT and GluR5 KO mice following subcutaneous implantation of placebo or morphine pellets. Surprisingly, spinal DYN and CGRP, along with phosphorylated ERK2 (pERK2), P38 (pP38) and PKCgamma (pPKCgamma) are elevated by deletion of GluR5. Additionally, chronic systemic morphine administration increased spinal pERK2, pP38 and pPKCgamma levels in both tolerant WT and non-tolerant GluR5 KO mice. In contrast, while morphine increased spinal DYN and CGRP in WT mice, DYN remained unchanged and CGRP was reduced in GluR5 KO mice. These observations suggest that spinal ERK2, P38 and PKCgamma are likely involved in multiple adaptive responses following systemic morphine administration, whereas DYN and CGRP may contribute selectively to the development of antinociceptive tolerance. PMID- 20359528 TI - Analgesic and anti-inflammatory effects of Pistacia integerrima extracts in mice. AB - AIM OF STUDY: Extracts of Pistacia integerrima galls have been dispensed by Traditional Practitioners of Subcontinent for chest diseases as well as for aches and pains in the body. This study was planned to evaluate the possible analgesic and antiinflammatory effects of Pistacia integerrima extracts. MATERIALS AND METHODS: Analgesia was determined using acetic acid induced abdominal constriction and formalin induced paw licking in mice. Antinociceptive effect was observed by thermally induced algesia in mice. RESULTS: Pistacia integerrima leaves extracts showed significant response against chemically induced pain (P<0.001) whereas galls extracts had highly significant protection (P<0.0001) in a dose dependent manner. In thermally induced algesia, Pistacia integerrima galls extracts 200 mg/kg (p.o.), showed significant (P<0.05) response but less than pentazocine and diclofenac, positive references. The extracts of Pistacia integerrima 50-200 mg/kg (p.o.) had modest activity against hind paw acute and chronic inflammation induced by formalin (P<0.01). CONCLUSION: These results demonstrate that Pistacia integerrima extracts have antinociceptive and analgesic effects and no apparent acute toxicity on oral administration. PMID- 20359529 TI - Full expression of Bacillus anthracis toxin gene in the presence of bicarbonate requires a 2.7-kb-long atxA mRNA that contains a terminator structure. AB - Bacillus anthracis toxin gene expression requires AtxA, a virulence regulator that also activates capsule gene transcription and controls expression of more than a hundred genes. Here we report that atxA mRNA is 2.7-kb-long and ends, after a 500 nt-long 3' untranslated region, with a stem loop structure followed by a run of U's. The presence of this structure stabilizes atxA mRNA and is necessary for AtxA maximal accumulation, full expression of the PA toxin gene, pagA and optimal PA accumulation. This structure displays terminator activity independently of its orientation when cloned between an inducible promoter and a reporter gene. The 3.6-kb-long DNA fragment carrying both AtxA promoters and the terminator is sufficient for full expression of pagA in the presence of bicarbonate. No pXO1-encoded element other than the DNA fragment encompassing the 2.7 kb atxA transcript and the pagA promoter is required for bicarbonate induction of pagA transcription. PMID- 20359530 TI - Therapeutic potential of endothelin receptor antagonists for chronic proteinuric renal disease in humans. AB - Diabetes and arterial hypertension continue to be the main causes of chronic renal failure in 2010, with a rising prevalence in part due to the worldwide obesity epidemic. Proteinuria is a main feature of chronic renal disease and mediated by defects in the glomerular filtration barrier and is as a good predictor of cardiovascular events. Indeed, chronic renal disease due to glomerulosclerosis is one of the important risk factors for the development of coronary artery disease and stroke. Glomerulosclerosis develops in response to inflammatory activation and increased growth factor production. Preclinical and first preliminary clinical studies provide strong evidence that endogenous endothelin-1 (ET-1), a 21-amino-acid peptide with strong growth-promoting and vasoconstricting properties, plays a central role in the pathogenesis of proteinuria and glomerulosclerosis via activation of its ET(A) subtype receptor involving podocyte injury. These studies have not only shown that endothelin participates in the disease processes of hypertension and glomerulosclerosis but also that features of chronic renal disease such as proteinuria and glomerulosclerosis are reversible processes. Remarkably, the protective effects of endothelin receptors antagonists (ERAs) are present even on top of concomitant treatments with inhibitors of the renin-angiotensin system. This review discusses current evidence for a role of endothelin for proteinuric renal disease and podocyte injury in diabetes and arterial hypertension and reviews the current status of endothelin receptor antagonists as a potential new treatment option in renal medicine. PMID- 20359532 TI - Gene delivery by lipoplexes and polyplexes. AB - Gene therapy has emerged as a promising approach for the treatment or prevention of acquired and genetic diseases. At the present time, major somatic gene transfer approaches employ either viral or non-viral vectors. Viral vectors show high gene transfer efficiency, but are deficient in several areas, including the induction of a host inflammatory and immune response. Some of these problems can be circumvented by employing non-viral vehicles, such as cationic liposomes or polymers. The complexes they form with DNA are defined as "lipoplexes" or "polyplexes, respectively, and constitute the most promising alternative to the use of viral vectors for gene therapy. Here we review the interactions between the vectors and DNA leading to complex formation, the supramolecular structures of lipoplexes and polyplexes, and their mechanisms of DNA transfer. Our objective is to provide a framework for the future design and synthesis of optimal non viral vectors for gene therapy. The structure, charge and formulation of these vehicles are also related to the stability, and consequently to the efficiency of gene transfection. While lipids that facilitate transformation of lipoplexes to non-bilayer phases mediate high transfection activity in vitro, lipids, like cholesterol, that confer stability in serum, are more suitable for gene delivery in vivo. The efficiency of polyplex-mediated transfection depends on the ability of the polymer to condense DNA, while allowing it to dissociate once inside the cell. PMID- 20359531 TI - Pharmacokinetic screening of soluble epoxide hydrolase inhibitors in dogs. AB - Epoxyeicosatrienoic acids that have anti-hypertensive and anti-inflammatory properties are mainly metabolized by soluble epoxide hydrolase (sEH, EC 3.3.2.3). Therefore, sEH has emerged as a therapeutic target for treating various cardiovascular diseases and inflammatory pain. N,N'-Disubstituted ureas are potent sEH inhibitors in vitro. However, in vivo usage of early sEH inhibitors has been limited by their low bioavailability and poor physiochemical properties. Therefore, a group of highly potent compounds with more drug-like physiochemical properties were evaluated by monitoring their plasma profiles in dogs treated orally with sEH inhibitors. Urea compounds with an adamantyl or a 4 trifluoromethoxyphenyl group on one side and a piperidyl or a cyclohexyl ether group on the other side of the urea function showed pharmacokinetic profiles with high plasma concentrations and long half lives. In particular, the inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) not only is very potent with good physiochemical properties, but also shows high oral bioavailability for doses ranging from 0.01 to 1mg/kg. This compound is also very potent against the sEH of several mammals, suggesting that t-AUCB will be an excellent tool to evaluate the biology of sEH in multiple animal models. Such compounds may also be a valuable lead for the development of veterinary therapeutics. PMID- 20359535 TI - Cancer stem cells: back to Darwin? AB - Current models of cancer propagation or 'stem' cells pay scant attention to the evolutionary dynamics of cancer or to the underlying genetic, mutational drivers. Recent genetic studies on acute lymphoblastic leukaemia at the single cell level reveal a complex non-linear, branching clonal architecture-with sub-clones having distinctive genetic signatures. Most cancers appropriately interrogated are found to have intra-clonal genetic heterogeneity indicative of divergent clonal evolution. These data further suggest that clonal architecture might be driven by genetic heterogeneity of propagating or 'stem' cells. When assayed for leukaemic regeneration in NOD/SCID/gamma mice, genetically diverse 'stem' cells read-out, broadly reflecting the clonal architecture. This has suggested a 'back to Darwin' model for cancer propagation. In this, cells with self-renewal potency or 'stem ness' provide genetically diverse units of evolutionary selection in cancer progression. The model has significant implications for targeted cancer therapy. PMID- 20359533 TI - Vitamin D inhibition of TACE and prevention of renal osteodystrophy and cardiovascular mortality. AB - In the course of kidney disease, the progressive loss of renal capacity to maintain normal serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) is a main contributor to parathyroid hyperplasia and high serum PTH. High PTH causes mineral and skeletal abnormalities predisposing to ectopic calcifications and increased mortality. Intriguingly, replacement therapy with 1,25(OH)2D or its less calcemic analogs was recently shown to improve survival in kidney disease patients through renal and cardiovascular protective actions that are independent of PTH suppression. This work presents preliminary evidence that 1,25(OH)2D inhibition of TACE (Tumor necrosis factor Alpha Converting Enzyme) is a potential common mechanism underlying the efficacy of therapy with 1,25(OH)2D or its analogs to improve outcomes in chronic kidney disease. 1,25(OH)2D prevents/moderates not only the onset and progression of parathyroid TACE/TGFalpha-driven secondary hyperparathyroidism, but, more significantly, renal TACE/TGFalpha-driven fibrotic and inflammatory lesions to the renal parenchyma, and TACE/TNFalpha-driven systemic inflammation, which is known to aggravate renal and cardiovascular lesions and enhance the risk of vascular calcification and cardiovascular mortality. PMID- 20359534 TI - Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia. AB - Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient global brain ischemia. RT-PCR and immunohistochemistry showed that the expression of TRAIL and DR5 was upregulated following transient ischemia-reperfusion. Dual immunofluorescence analysis indicated that TRAIL expression was significantly more pronounced in astrocytes and activated microglia/macrophages, whereas DR5 expression was more pronounced in neurons, which had a good correlation with the distribution of apoptotic cells. Treatment with soluble DR5 reduced ischemic cell death after transient global ischemia through blocking the interaction of endogenous TRAIL with DR5. These results indicate that TRAIL plays a deleterious role in the pathogenesis of delayed neuronal damage after global cerebral ischemia and inhibition of TRAIL function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke. PMID- 20359536 TI - Drug discovery in the p53 field. PMID- 20359537 TI - Characteristics of an extensive Mycobacterium avium subspecies paratuberculosis recombinant protein set. AB - In the first step of a comprehensive large-scale antigen discovery project, 651 genes of Mycobacterium avium subspecies paratuberculosis were expressed in Escherichia coli. All of these were purified by affinity chromatography, dialyzed in phosphate buffered saline, and analyzed on SDS-PAGE gels. Collectively, these purified recombinant proteins represent 14.9% of the total M. avium subsp. paratuberculosis proteome. This volume of protein expression and purification has yielded unique observations that may be missed in smaller scale expression and purification projects. For example, the 252 putative membrane proteins predicted by PSORTb analysis, resulted in lower average expression yields (3.51mg/l culture) than the 176 predicted cytoplasmic proteins (7.27mg/l culture). A few proteins (MAP0107c, MAP3169c and MAP3640) appear to promote lysis of E. coli since there was a drop in optical density of the growth culture minutes after the inducing agent was added. Certain M. avium subsp. paratuberculosis proteins, when expressed in E. coli changed the color of the column resin or appearance of harvested cell pellets. Finally, 19 proteins showed an absorbance maximum at 260nm rather than 280nm that was attributed to binding of nucleic acid during purification. This extensive recombinant protein repository provides a powerful tool for proteome- and genome-scale research of this organism. PMID- 20359538 TI - A software tool to accelerate design of protein constructs for recombinant expression. AB - Structural and biochemical analysis of proteins requires access to purified protein material. Modern molecular biology technologies facilitate straightforward molecular cloning and expression analysis of multiple protein constructs in parallel, and such approaches have proven very efficient to identify samples suitable for further analysis. A variety of information can be used to support rational design of protein constructs. This includes, e.g. prediction of secondary structure elements, protein domain predictions, and structure prediction methods such as threading. To fully access the available information, collation of data extracted from several different sources is required. This can be cumbersome and sometimes also confusing due to for example different implementation of amino acid residue numbering schemes. The SGC Domain Boundary Analyser tool provides a graphical interface that simplifies and accelerates rational design of protein expression constructs. PMID- 20359539 TI - A reappraisal of the evolution of Asian snakehead fishes (Pisces, Channidae) using molecular data from multiple genes and fossil calibration. AB - Freshwater snakehead fishes (Channidae) provide an interesting target for phylogenetic analysis for the following reasons, their unusual biology, potential for cryptic diversity and availability of a good fossil record. Here, a multi locus molecular phylogeny was constructed and calibrated using two fossil dates to estimate divergence times within the family. Sampling aimed to explore interspecific divergence of Channa species across Southeast Asia and intra specific variation where species possessed natural geographical ranges that were extensive. Results contradict divergence times estimated previously independently from single locus mitochondrial data or the fossil record and suggest that after divergence from African taxa 40-50 Ma, evolution of Asian snakeheads has been heavily influenced by multiple broad scale dispersal events across India and Southeast Asia. A similar pattern of divergence within multiple clades suggests that west-east dispersal was limited for many taxa during the Miocene. Deep intra specific divergence was inferred for C. striata, indicating that long historical periods of isolation ( approximately 8Ma) have not resulted in the evolution of reproductive isolation within this species. Results support suggestions that C. marulia like fishes in northern Cambodia may constitute an undescribed species, and that Indian C. diplogramma warrants taxonomic recognition as being distinct from Southeast Asian C. micropeltes, with the two taxa last sharing a common ancestor in the mid- to late-Miocene. PMID- 20359541 TI - Gene expression profile in rat hippocampus with and without memory deficit. AB - The cholinergic neuronal system, through its projections to the hippocampus, plays an important role in learning and memory. The aim of the study was to identify genes and networks in rat hippocampus with and without memory deficit. Genome-scale screening was used to analyze gene expression changes in rats submitted or not to intraparenchymal injection of 192 IgG-saporin and trained in spatial/object novelty tasks. Results showed learning processes were associated with significant expression of genes that could be grouped into several clusters of similar expression profiles and that are involved in biological functions, namely lipid metabolism, signal transduction, protein metabolism and modification, and transcription regulation. Memory loss following hippocampal cholinergic deafferentation was associated with significant expression of genes that did not show similar cluster organization. Only one cluster of genes could be identified; it included genes that would be involved in tissue remodeling. More important, most of the genes significantly altered in lesioned rats were down-regulated. PMID- 20359543 TI - miRNAs in the biogenesis of trans-acting siRNAs in higher plants. AB - Multicellular eukaryotes utilize many complex small RNA mechanisms to regulate gene expression from DNA modifications to RNA stability. RNA interference also regulates exogenous gene expression by degrading invading pathogen RNAs or preventing expression of foreign DNA incorporated into the host genome. Here we review the mechanisms for trans-acting (ta)-siRNA biogenesis and function, including pathways that utilize components of the miRNA and transitive RNAi defense. There are several distinguishing features of ta-siRNA pathways including the requirement for a miRNA-guided cleavage event that sets a processing register, RDR6 dependent dsRNA production, and DCL4 dependent processing to create unique, phased 21 nucleotide small RNAs. These phased small RNAs function to suppress target genes that only show similarity at the ta-siRNA recognition site, and act in trans to repress expression non-cell autonomously of specific target genes. Since the advent of high throughput sequencing technologies, phased siRNAs have been identified in a number of organisms [Heisel SE, Zhang Y, Allen E, Guo L, Reynolds TL, Yang X, et al. Characterization of unique small RNA populations from rice grain. PLoS One 2008;3:e2871. Zhao T, Li G, Mi S, Li S, Hannon GJ, Wang XJ, et al. A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev 2007;21:1190-203. Johnson C, et al. Clusters and superclusters of phased small RNAs in the developing inflorescence of rice. Genome Res 2009;19:1429-40. Zhu QH, Spriggs A, Matthew L, Fan L, Kennedy G, Gubler F, et al. A diverse set of microRNAs and microRNA-like small RNAs in developing rice grains. Genome Res 2008;18:1456-65. Howell MD, Fahlgren N, Chapman EJ, Cumbie JS, Sullivan CM, Givan SA, et al. Genome-wide analysis of the RNA-DEPENDENT RNA POLYMERASE6/DICER-LIKE4 pathway in Arabidopsis reveals dependency on miRNA- and ta-siRNA-directed targeting. Plant Cell 2007;19:926-42.]. These include transcripts generated either from non-protein coding or protein-coding transcripts, long imperfect dsRNA or through an unknown mechanism; therefore some of these may not necessarily be classified as canonical ta-siRNAs. PMID- 20359542 TI - Regulation of macroautophagy in Saccharomyces cerevisiae. AB - Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation. In this process, a double membrane vesicle, an autophagosome, surrounds part of the cytoplasm and fuses with the vacuole to allow the breakdown and subsequent recycling of the cargo. In yeast, many autophagy-related (ATG) genes have been identified that are required for selective and/or nonselective autophagy. In all autophagy-related pathways, core Atg proteins are required for the formation of the autophagosome, which is one of the most unique aspects of autophagy and is unlike other vesicle transport events. In contrast to nonselective autophagy, the selective processes are induced in response to various specific physiological conditions such as alterations in the carbon source. In this review, we provide an overview of the common aspects concerning the mechanism of autophagy-related pathways, and highlight recent advances in our understanding of the machinery that controls autophagy induction in response to nutrient starvation conditions. PMID- 20359544 TI - Transforming growth factor-beta expression by host cells is elicited locally by the filarial nematode Onchocerca volvulus in hyporeactive patients independently from Wolbachia. AB - Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local release of immunosuppressive cytokines. Therefore, using immunohistology, we investigated the expression of stable, released latent TGF-beta1 in subcutaneous nodules from highly infected, hyporeactive onchocerciasis patients, harbouring adult Onchocerca volvulus. Since many cell types produce TGF-beta, we elucidated the cellular source, distribution and dependency on the worms' sex, productivity and vitality. We found TGF-beta1 to be abundantly expressed by T cells, plasma/B cells, macrophages, mast cells, fibrocytes, and vascular endothelial cells, particularly in onchocercomas with productive or previously productive females, damaged, dead and resorbed adult worms or microfilariae. We conclude TGF-beta to be antigen induced by the filariae since expression was scarce around subcutaneous arthropods or cholesterol crystals in onchocercomas. Enhanced expression after ivermectin or endobacteria-depleting doxycycline treatment indicates induction to depend on filariae and not on Wolbachia endobacteria. TGF-beta(+) cells were reduced in HIV co-infection. This finding of local and sustained TGF-beta induction by vital and dead filariae, untreated and after treatment, adds new aspects to immunomodulation by helminths. PMID- 20359545 TI - New strategies to improve the intranasal absorption of insulin. AB - Recently, intranasal delivery of insulin as an alternative route of parenteral administration has been widely studied because it bears close resemblance to the 'pulsatile' pattern of endogenous insulin secretion during meal time. However, insulin is not well absorbed through nasal mucosa because of its large molecular size, hydrophilicity and low permeability through the membrane. This review describes the main barriers preventing nasal insulin absorption, and special attention is given to new approaches to improve the intranasal absorption of insulin, including the application of new safe absorption enhancers and the use of appropriate delivery systems. It seems that bioadhesive delivery systems or water-insoluble powders with absorption enhancers are the most promising methods for intranasal delivery of insulin. PMID- 20359546 TI - Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1. AB - GPR55 is a seven-transmembrane G-protein-coupled receptor that has been proposed as a novel type of cannabinoid receptor. Previously, we identified lysophosphatidylinositol (LPI), in particular 2-arachidonoyl-LPI, as an agonist for GPR55. In the present study, we examined whether intracellular phospholipase A1 (DDHD domain containing 1, or DDHD1), previously identified as phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), is involved in the formation of 2 arachidonoyl-LPI. HEK293 cells expressing DDHD1 produced [(3)H]arachidonic acid containing LPI after prelabeling with [(3)H]arachidonic acid and subsequent activation by ionomycin; the formation of [(3)H]LPI was inhibited by n-butanol and the overexpression of an inactive PLD1 mutant PLD1K898R. DDHD1 was translocated from the cytosol to membranes upon ionomycin treatment. A purified recombinant DDHD1 formed [(3)H]LPI when incubated with [(3)H]PI; the V(max) and apparent K(m) were 190 micromol/min/mg protein and 10 mol% PI, respectively. DDHD1 binds PA, and the addition of PA to DDHD1 increased the affinity for PI (K(m) ; 3 mol%) and augmented the PI-PLA1 activity. DDHD1 activated by PA was returned to a basal state by its own PA-hydrolytic activity. These results implicate DDHD1 in the formation of 2-arachidonoyl-LPI and indicate that the process is modulated by PA released by phospholipase D. Similar observations for the production of arachidonic acid-containing LPI in neuroblastoma cells suggest the DDHD1-LPI-GPR55 axis to be involved in functions in the brain. PMID- 20359547 TI - Brain cholesterol in normal and pathological aging. AB - Correct lipid homeostasis at the plasma membrane is essential for cell survival and performance. These are critically challenged in the aging brain. Changes in the levels of cholesterol, a major membrane component especially enriched in neurons, accompany the brain aging process. They also occur in neurodegenerative diseases. Understanding the causes and consequences of these changes is a crucial step when trying to delay the cognitive decline, which comes with age, or to design strategies to fight neurodegenerative disorders such as Alzheimer's disease. We here review work that has contributed to this understanding. PMID- 20359548 TI - Proclets in healthcare. AB - Healthcare processes can be characterized as weakly-connected interacting light weight workflows coping with different levels of granularity. Classical workflow notations fall short in supporting these kind of processes. Although these notations are able to describe the life-cycle of individual cases and allow for hierarchical decomposition, they primarily support monolithic processes. However, they are less suitable for healthcare processes. The Proclets framework is one formalism that provides a solution to this problem. Based on a large case study, describing the diagnostic process of the gynecological oncology care process at the Academic Medical Center (AMC), we identify the limitations of "monolithic workflows". Moreover, by using the same case study, we investigate whether healthcare processes can be described effectively using Proclets. In this way, we provide a comparison between the Proclet framework and existing workflow languages and identify research challenges. PMID- 20359550 TI - Role of the IFNG +874T/A polymorphism in Chagas disease in a Colombian population. AB - Genetic susceptibility to Trypanosoma cruzi infection and the development of cardiomyopathy is complex, heterogeneous, and likely involves several genes. Previous studies have implicated cytokine and chemokine genes in susceptibility to Chagas disease. Here we investigated the association between the interferon gamma gene (IFNG) +874T/A polymorphism and Chagas disease, focusing on susceptibility and severity. This study included 236 chagasic patients (asymptomatic, n=116; cardiomyopathic, n=120) and 282 healthy controls from a Colombian population where T. cruzi is highly endemic. Individuals were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) of the IFNG gene by amplification refractory mutational system PCR (ARMS-PCR). Moreover, clinical manifestations of Chagas in patients were analyzed. We found a significant difference in the distribution of the IFNG +874 "A" allele between patients and healthy controls (P=0.003; OR=1.46, 95% CI, 1.13-1.89). The frequency of the IFNG +874 genotype A/A, which is associated with reduced production of interferon-gamma, was increased in the patients relative to controls (38.1% vs. 26.6%). We compared the frequencies of IFNG alleles and genotypes between asymptomatic patients and those with chagasic cardiomyopathy and found no significant difference. Our data suggest that the IFNG +874T/A genetic polymorphism may be involved in susceptibility but not in the progression of Chagas disease in this Colombian population. PMID- 20359549 TI - The faith, activity, and nutrition (FAN) program: design of a participatory research intervention to increase physical activity and improve dietary habits in African American churches. AB - BACKGROUND: African Americans are at increased risk for cardiovascular disease and cancer morbidity and mortality. Physical activity and healthy dietary practices can reduce this risk. The church is a promising setting to address health disparities, and community-based participatory research is a preferred approach. OBJECTIVES: Using a community-based participatory approach and the social ecologic model, the FAN trial aims to increase self-reported moderate intensity physical activity and fruit and vegetable consumption and reduce blood pressure in African American church members. Secondary aims are to increase objectively measured moderate-intensity physical activity and fiber/whole grain consumption and reduce fat consumption. DESIGN: FAN is a group randomized trial (GRT) with two levels of clustering: participants (N=1279; n=316 accelerometer subgroup) within church and church within church cluster. In the first wave, seven clusters including 23 churches were randomized to an immediate intervention or delayed intervention. In subsequent waves, 51 churches were randomized to an immediate or delayed intervention. METHODS: Church committee members, pastors, and cooks participate in full-day trainings to learn how to implement physical activity and dietary changes in the church. Monthly mailings and technical assistance calls are delivered over the 15-month intervention. Members complete measurements at baseline and 15 months. A detailed process evaluation is included. SUMMARY: FAN focuses on modifying the social, cultural, and policy environment in a faith-based setting. The use of a community-based participatory research approach, engagement of church leaders, inclusion of a detailed process evaluation, and a formal plan for sustainability and dissemination make FAN unique. PMID- 20359551 TI - Inbreeding depression affects life-history traits but not infection by Plasmodium gallinaceum in the Asian tiger mosquito, Aedes albopictus. AB - Emerging and re-emerging vector-borne diseases represent an increasingly significant public health challenge. While geographic variation among populations of vector species for susceptibility to pathogen infection and vector competence has been thoroughly documented, relatively little attention has been devoted to understanding the ultimate evolutionary causes of this intraspecific variation. Local genetic drift is known to influence genetic differentiation among populations for a variety of container-inhabiting mosquito species, including Aedes albopictus. Because genetic drift is expected to reduce genetic variation and lead to the accumulation of (partially) recessive deleterious alleles, we hypothesized that reduced genetic variation might affect susceptibility to pathogen infection in a model pathogen-vector system. We therefore created replicate inbred (two generations of full-sib mating, expected f=0.375) and control (expected f approximately 0.07) lines of Ae. albopictus and measured life history traits including larval survivorship, adult longevity, and female wing length (body size) as well as susceptibility to infection by a model pathogen, Plasmodium gallinaceum. Inbred mosquitoes had significantly reduced larval survivorship and female adult longevity but inbreeding did not affect male adult longevity or female wing length (body size). Furthermore, there was no effect of inbreeding on susceptibility to infection by P. gallinaceum. Therefore, while our results did not support the hypothesis that reduced genetic variation influences susceptibility to pathogen infection in this system, we did find evidence for an effect of reduced genetic variation on female adult longevity, an important component of vectorial capacity. We suggest that additional research is needed to elucidate the genetic underpinnings of intraspecific variation in traits related to disease transmission and discuss the implications of our results for the efficacy of creating transgenic strains refractory to disease transmission. PMID- 20359552 TI - Simvastatin attenuates acrolein-induced mucin production in rats: involvement of the Ras/extracellular signal-regulated kinase pathway. AB - Airway mucus overproduction is a cardinal feature of airway inflammatory diseases, such as chronic obstructive pulmonary disease and cystic fibrosis. Since the small G-protein Ras is known to modulate cellular functions in the lung, we sought to investigate whether the Ras inhibitor simvastatin could attenuate acrolein-induced mucin production in rat airways. Rats were exposed to acrolein for 12 days, after first being pretreated intragastrically for 24 h with either simvastatin alone or simvastatin in combination with mevalonate, which prevents the isoprenylation needed for Ras activation. Lung tissue was analyzed for extracellular signal-regulated kinase (ERK) activity, goblet cell metaplasia and mucin production. To analyze the effect of simvastatin on mucin production in more detail, acrolein-exposed human airway epithelial NCI-H292 cells were pretreated with simvastatin alone or together with mevalonate. Culture medium was collected to detect mucin secretion, and cell lysates were examined for Ras GTPase activity and epidermal growth factor receptor (EGFR)/ERK phosphorylation. In vivo, simvastatin treatment dose-dependently suppressed acrolein-induced goblet cell hyperplasia and metaplasia in bronchial epithelium and inhibited ERK phosphorylation in rat lung homogenates. Moreover, simvastatin inhibited Muc5AC mucin synthesis at both the mRNA and protein levels in the lung. In vitro, simvastatin pretreatment attenuated the acrolein-induced significant increase in MUC5AC mucin expression, Ras-GTPase activity and EGFR/ERK phosphorylation. These inhibitory effects of simvastatin were neutralized by mevalonate administration both in vitro and in vivo. Our results suggest that simvastatin may attenuate acrolein-induced mucin protein synthesis in the airway and airway inflammation, possibly by blocking ERK activation mediated by Ras protein isoprenylation. Thus, the evidence from the experiment suggests that human trials are warranted to determine the potential safety and efficacy of simvastatin for treatment of over production of airway mucus. PMID- 20359554 TI - Development of bone-like composites via the polymer-induced liquid-precursor (PILP) process. Part 1: influence of polymer molecular weight. AB - Bone is an organic-inorganic composite consisting primarily of collagen fibrils and hydroxyapatite crystals intricately interlocked to provide skeletal and metabolic functions. Non-collagenous proteins (NCPs) are also present, and although only a minor component, the NCPs are thought to play an important role in modulating the mineralization process. During secondary bone formation, an interpenetrating structure is created by intrafibrillar mineralization of the collagen matrix. Many researchers have tried to develop bone-like collagen hydroxyapatite (HA) composites via the conventional crystallization process of nucleation and growth. While those methods have been successful in inducing heterogeneous nucleation of HA on the surface of collagen scaffolds, they have failed to produce a composite with the interpenetrating nanostructured architecture of bone. Our group has shown that intrafibrillar mineralization of type I collagen can be achieved using a polymer-induced liquid-precursor (PILP) process. In this process, acidic polypeptides are included in the mineralization solution to mimic the function of the acidic NCPs, and in vitro studies have found that acidic peptides such as polyaspartate induce a liquid-phase amorphous mineral precursor. Using this PILP process, we have been able to prepare collagen HA composites with the fundamental nanostructure of bone, wherein HA nanocrystals are embedded within the collagen fibrils. This study shows that through further optimization a very high degree of mineralization can be achieved, with compositions matching that of bone. Synthetic collagen sponges were mineralized with calcium phosphate while analyzing various parameters of the reaction, with the focus of this report on the molecular weight of the polymeric process directing agent. In order to determine whether intrafibrillar mineralization was achieved, an in-depth characterization of the mineralized composites was performed, including wide-angle X-ray diffraction, electron microscopy and thermogravimetric analyses. The results of this work lead us closer to the development of bone-like collagen-HA composites that could become the next generation of synthetic bone grafts. PMID- 20359553 TI - Role of central neurotransmission and chemoreception on airway control. AB - This review summarizes work on central neurotransmission, chemoreception and CNS control of cholinergic outflow to the airways. First, we describe the neural transmission of bronchoconstrictive signals from airway afferents to the airway related vagal preganglionic neurons (AVPNs) via the nucleus of the solitary tract (nTS) and, second, we characterize evidence for a modulatory effect of excitatory glutamatergic, and inhibitory GABAergic, noradrenergic and serotonergic pathways on AVPN output. Excitatory signals arising from bronchopulmonary afferents and/or the peripheral chemosensory system activate second order neurons within the nTS, via a glutamate-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor signaling pathway. These nTS neurons, using the same neurotransmitter receptor unit, transmit information to the AVPNs, which in turn convey the central command through descending fibers and airway intramural ganglia to airway smooth muscle, submucosal secretory glands, and the vasculature. The strength and duration of this reflex-induced bronchoconstriction is modulated by GABAergic inhibitory inputs. In addition, central noradrenergic and serotonergic inhibitory pathways appear to participate in the regulation of cholinergic drive to the tracheobronchial system. Down-regulation of these inhibitory influences results in a shift from inhibitory to excitatory drive, which may lead to increased excitability of AVPNs, heightened airway responsiveness, greater cholinergic outflow to the airways and consequently bronchoconstriction. In summary, centrally coordinated control of airway tone and respiratory drive serve to optimize gas exchange and work of breathing under normal homeostatic conditions. Greater understanding of this process should enhance our understanding of its disruption under pathophysiologic states. PMID- 20359555 TI - Mechanical properties, electronic structure and bonding of alpha- and beta tricalcium phosphates with surface characterization. AB - The mechanical properties and electronic structure of alpha- and beta-tricalcium phosphate (TCP) crystals are studied by using two ab initio density functional methods, the Vienna Ab initio Simulation Package (VASP) and the orthogonalized linear combination of atomic orbitals method. Based on the VASP optimized crystal structures, the elastic constants of alpha- and beta-TCP are obtained using an effective stress-strain computational scheme. From the calculated elastic constants, the bulk modulus, shear modulus, Young's modulus and Poisson's ratios are obtained. The results show that the mechanical properties of the two crystals are comparable and that alpha-TCP is somewhat softer than beta-TCP. Comparison with experimental extrapolations of the elastic constants shows significant differences, which attest to the difficulty of obtaining single crystal samples. The calculated electronic structure results show that both crystals are large gap insulators with a direct band gap of 4.89 eV for alpha-TCP and 5.25 eV for beta TCP. Effective charge calculations show that, on average, beta-TCP has slightly less charge transfer per Ca than alpha-TCP. The (010) ((001)) surface model for alpha-TCP (beta-TCP) is studied using a supercell slab geometry and fully relaxed to obtain the optimized structures. The estimated surface formation energies are 0.777 and 0.842 J m(-2) for alpha-TCP and beta-TCP, respectively. The electronic structures of the two surface models are compared with the bulk models. Charge density analysis shows that the surfaces of both TCP crystals are positively charged overall owing to the presence of Ca ions near the surfaces. PMID- 20359556 TI - Alginate-controlled formation of nanoscale calcium carbonate and hydroxyapatite mineral phase within hydrogel networks. AB - A one-step method was used to make nanostructured composites from alginate and calcium carbonate or calcium phosphate. Nanometer-scale mineral phase was successfully formed within the gel network of alginate gel beads, and the composites were characterized. It was found that calcite was the dominating polymorph in the calcium carbonate mineralized beads, while stoichiometric hydroxyapatite was formed in the calcium phosphate mineralized beads. A combination of electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis and powder X-ray diffraction showed that alginate played an active role in controlling mineral size, morphology and polymorphy. For the calcium phosphate mineralized beads, alginate was shown to modulate stoichiometric hydroxyapatite with low crystallinity at room temperature, which may have important applications in tissue engineering. The results presented in this work demonstrate important aspects of alginate-controlled crystallization, which contributes to the understanding of composite material design. PMID- 20359557 TI - Clinical presentations, diagnosis and treatment of adult intussusception, a 20 years survey. AB - BACKGROUND: Intussusception is a rare cause of intestinal obstruction in adult patients. The etiology of malignant nature has been reported to be more frequent in this group and the diagnosis is usually made at operation. Few reports are published for this clinical entity from Middle East. METHODS: The medical records of all adult patients admitted with the diagnosis of intussusception in a tertiary care center between 1989 and 2009 were reviewed. RESULTS: There were 15 cases of intussusception in this 20 years period. The mean age of patients was 33.6 years, 8 females and 7 males. In 14 cases the leading point of intussusception was in small bowel. Resection and primary anastomosis was the selected procedure in 13 patients; one patient underwent colostomy and one reduction alone. Malignant cause was detected in only 2 cases. 7 Patients were operated on with diagnosis of intussusception according to imaging findings. The diagnosis was made at operation in the remaining 8 cases. Only one anastomotic leakage occurred in patient on systemic steroids. CONCLUSION: The mean age of our patients is relatively low with more benign etiologies in small bowel. The CT scan may be the most helpful imaging modality in suspected cases but decision for operation in acute presentations should not be deferred for definite diagnosis. Resection of the involved bowel segment and primary anastomosis is associated with a good outcome. PMID- 20359558 TI - Popular misconceptions: agricultural biotechnology. AB - Agricultural biotechnology, especially genetic engineering or genetic modification (GM), is a topic of considerable controversy worldwide. The public debate is fraught with polarized views and opinions, some are held with religious zeal. Unfortunately, it is also marked with much ignorance and misinformation. Here we explore some popular misconceptions encountered in the public debate. PMID- 20359559 TI - A flexible and fully integrated system for amplification, detection and genotyping of genomic DNA targets based on microfluidic oligonucleotide arrays. AB - A strategy allowing for amplification, detection and genotyping of different genomic DNA targets in a single reaction container is described. The method makes use of primer-directed solution-phase amplification with integrated labeling in a closed, microfluidic oligonucleotide array. Selective array probes allow for subsequent detection and genotyping of generated amplicons by hybridization. The array contains up to 15,624 programmable features that can be designed, de novo synthesized and tested within 24 hours using an automated benchtop microarray synthesizer. This enables rapid prototyping and adaptation of the system to newly emerging targets such as pathogenic bacterial or viral subtypes. The system was evaluated by amplifying and detecting different loci of viral (HPV), bacterial (Bacillus sp.) and eukaryotic (human) genomes. Multiplex PCR and semi quantitative detection with excellent detection limits of <100 target copies is hereby demonstrated. The high automation grade of the system reduces contamination risk and workload and should enhance safety and reproducibility. PMID- 20359560 TI - A dynamic model of pneumococcal infection in the United States: implications for prevention through vaccination. AB - Universal infant vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) has nearly eliminated PCV7-serotype invasive pneumococcal disease (IPD) in young U.S. children, but has been accompanied by increases in the incidence of serotype 19A IPD. Because antibiotic-non-susceptible 19A has increased more than antibiotic-susceptible 19A, antibiotic selection pressure could be contributing to this trend. We developed a dynamic compartmental transmission model of pneumococcus to better understand the causes of this rise and to estimate the impact of vaccines or changes in antibiotic use on future IPD incidence in the U.S. in <2 year-olds. The model predicted that with current practices, serotype 19A IPD incidence will plateau at about the 2007 level over the next few years. The model suggests that antibiotic usage played a major role in the rise in antibiotic-non-susceptible 19A IPD, with a lesser contribution from PCV7 vaccination. However, hypothetical large decreases in antibiotic use starting in 2008 are predicted to yield only gradual decreases in antibiotic-non-susceptible 19A IPD. On the other hand, vaccines with modest (20%) effectiveness against 19A (or 6A or PCV7-serotypes) carriage are predicted to substantially (by 80%) decrease the incidence of IPD caused by those serotypes within 10 years of implementation. Our findings highlight that vaccine effects on colonization are key to their overall benefits. In addition, serotype changes following vaccine introduction may have multifactorial origins, with antibiotic use an important factor for resistant strains such as 19A. PMID- 20359561 TI - A novel mitogen fusion protein against CD40+ cells with potent vaccine adjuvant properties. AB - A large number of infectious diseases caused by viral or bacterial infections are treatable and/or preventable by vaccination. In addition, ongoing research is aimed at the development of vaccines against other types of diseases, including almost all forms of cancer. The efficacy of a vaccine relies on the antigen specific response by the entire repertoire of immune competent cells. Here, we have generated a powerful mitogen fusion protein, CD40L-FasL-IgFc, which stimulates CD40(+) cells robustly. We found that this specific cell activation is accompanied by increased expression of PRDI-BF1 (Blim-1) RNA, an indicator of terminal B-cell differentiation, in cultures stimulated with CD40L-FasL-IgFc. The addition of specific inhibitors of NF-kappaB and MEK1/2 partially suppressed the observed proliferative effects of CD40L-FasL-IgFc. When tested in vivo, the immune response to influenza HA vaccine was significantly increased by co administration of CD40L-FasL-IgFc. Moreover, the co-administration of the cDNA expression plasmid encoding CD40L-FasL-IgFc significantly boosted the vaccine response. We now have a unique opportunity to evaluate our novel fusion protein adjuvant, and other similarly constructed fusion proteins, in both protein-based and genetic vaccines. PMID- 20359562 TI - Squamous cell carcinoma arising from the pleura after pneumonectomy for squamous cell carcinoma of the lung. AB - BACKGROUND: A 67-year-old Caucasian man had a right pneumonectomy for primary bronchogenic carcinoma in 1998. He developed a bronchopleural fistula that was managed with an Eloesser procedure. His appearance 6 years later has been published previously. METHODS: We performed a case report and literature search. RESULTS: In 2008, the patient still had a bronchopleural fistula and reported a new symptom: constant right chest pain. He had experienced extensive asbestos exposure and mesothelioma was suspected. Endoscopy via the Eloesser aperture revealed innumerable tumor nodules. Biopsies of the pleura revealed multifocal, well-differentiated, squamous cell carcinoma with histology that was distinctly different from that of the original lung cancer. The tumor progressed rapidly during work-up and invaded the spine. He received palliative treatment but died 4 months after the onset of chest pain. We conducted a literature search and found 9 previous reports of epidermoid carcinoma arising from the pleura in patients with a chronically draining empyema; 5 patients had a prior pneumonectomy. CONCLUSIONS: Cancer can arise in areas of chronic inflammation such as osteomyelitis with a draining sinus, Crohn's disease, or chronic gastritis. Cases of squamous cell carcinoma arising from the pleura in patients with a chronically draining empyema cavity are extremely rare. We believe this is the sixth report in the literature of squamous cell carcinoma arising from the pleura in a patient with a chronic postpneumonectomy bronchopleural fistula. In vivo video footage of the involved pleura is available PMID- 20359563 TI - Pelvic retroperitoneal leiomyoma. AB - Primary retroperitoneal leiomyomas are a rare and unusual differential diagnosis in the acute abdomen. A 26-year-old woman presented with chronic constipation and acute abdominal pain. The diagnostic workup included contrast computer tomography, transabdominal ultrasonography, and colonoscopy that revealed an 8-cm homogeneous pelvic tumor with rectal compression. Retroperitoneal leiomyoma was suspected on imaging studies and finally confirmed after tumor excision and immunohistochemical staining. PMID- 20359564 TI - Pure hepatoid adenocarcinoma of the stomach with spleen and lymph-node metastases. AB - The authors report a rare case of hepatoid adenocarcinoma of the stomach, presenting initially with spleen and lymph node metastases. PMID- 20359565 TI - Enterolith ileus due to jejunal diverticulosis. AB - Jejunal diverticulosis is a rare malformation that is often asymptomatic. Complications might be similar to those occurring in large-bowel diverticula but also include a much more particular event: intestinal obstruction due to migration and impaction of enterolith formed inside diverticula. This is a very uncommon entity; diagnosis and management are thus often delayed. Mostly surgical exploration is necessary because obstruction symptoms are unresponsive to medical treatment. The authors report a new case of enterolith ileus in a 74-year-old man, due to jejunal diverticulosis, and its successful surgical management in emergency. Only 39 similar cases have ever been reported in the literature. PMID- 20359566 TI - Pacifying the open abdomen with concomitant intestinal fistula: a novel approach. AB - The management of the open abdomen, particularly when complicated by the presence of intestinal fistula, remains a significant challenge of modern trauma care. Although several approaches have been proposed, these varied and complex cases defy the application of a universal approach to local therapy. Ultimately, abdominal closure is desired but is not always possible. Accordingly, surgeons must be well versed in the application of a number of useful approaches that may serve to facilitate control of fistula drainage while permitting management of the surrounding open wound. We contribute a management approach that is simplistic in design, provides for effective fistula control, and permits the subsequent unhindered granulation of the surrounding wound in abdomens not amenable to delayed closure techniques. PMID- 20359567 TI - Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer. AB - BACKGROUND: Neoadjuvant chemotherapy reduces tumor size before surgery in women with breast cancer. The aim of this study was to assess the ability of mammography and ultrasound to predict residual tumor size following neoadjuvant chemotherapy. METHODS: In a retrospective review of consecutive breast cancer patients treated with neoadjuvant chemotherapy, residual tumor size estimated by diagnostic imaging was compared with residual tumor size determined by surgical pathology. RESULTS: One hundred ninety-two patients with 196 primary breast cancers were studied. Of 104 tumors evaluated by both imaging modalities, ultrasound was able to size 91.3%, and mammography was able to size only 51.9% (chi(2)P < .001). Ultrasound also was more accurate than mammography in estimating residual tumor size (62 of 104 [59.6%] vs 33 of 104 [31.7%], P < .001). There was little difference in the ability of mammography and ultrasound to predict pathologic complete response (receiver operating characteristic, 0.741 vs 0.784). CONCLUSIONS: Breast ultrasound was more accurate than mammography in predicting residual tumor size following neoadjuvant chemotherapy. The likelihood of a complete pathologic response was 80% when both imaging modalities demonstrated no residual disease. PMID- 20359568 TI - Surgical drains can be safely avoided in lateral neck dissections for papillary thyroid cancer. AB - BACKGROUND: Drains are widely used in lateral neck dissections (LNDs). Our objective was to compare outcomes of LNDs for papillary thyroid cancer (PTC) with and without drains. METHODS: One hundred sixty-five LNDs in 129 patients operated on from July 2001 to October 2008 were analyzed retrospectively. LNDs were divided according to the number of excised lymph nodes as follows: group A < median and group B > median. Further categorization was based on the use of a drain. Main outcome measures were wound complications requiring intervention. RESULTS: One hundred two LNDs were performed with a drain and 63 without. The overall rate of wound complications was 3%. There was no significant difference in complication rate between the drain and the non-drain group (group A: 1.8% vs 0; group B: 2.2% vs 7.9%, respectively). CONCLUSIONS: Significant seromas/hematomas are rare complications of LNDs. Patients who undergo LND for PTC without a drain show no significantly increased rate of these complications. PMID- 20359569 TI - Breast cancer treatment beliefs and influences among surgeons in areas of scientific uncertainty. AB - BACKGROUND: Breast cancer treatment beliefs in areas of scientific uncertainty may contribute to widely variable practices. We sought to better describe surgeons' beliefs and to identify the relative importance of different information sources on surgeons' decision-making. METHODS: A total of 2,188 American College of Surgeons (ACoS) members were surveyed on their treatment beliefs in 4 controversial areas and on the perceived influence of various information sources on their decision-making. Responses were analyzed by sex, practice type, oncology training, professional society membership, and breast cancer patient volume. RESULTS: Nine hundred twenty-three responses were received, with 459 eligible for analysis. Responses diverged most regarding significance of positive sentinel lymph node biopsy (SNLB) and role of post lumpectomy radiation for low-risk ductal carcinoma-in-situ (DCIS). Overall, expert opinion ranked as the most influential information source. CONCLUSIONS: Axillary dissection after positive SLNB and post-lumpectomy radiation in low-risk DCIS denoted areas of greater uncertainty. Breast cancer opinion leaders have substantial influence when standard practice is uncertain. PMID- 20359570 TI - A new vagal anchor electrode for real-time monitoring of the recurrent laryngeal nerve. AB - BACKGROUND: Despite conventional neuromonitoring, the recurrent laryngeal nerve (RLN) is still at risk for damage during thyroid surgery. The feasibility of continuous RLN monitoring by vagal nerve (VN) stimulation with a new anchor electrode should be shown, and electromyographic signal alterations of stressed RLN were analyzed to be alerted to imminent nerve failure whereby the nerve damage becomes reversible. METHODS: VN stimulation was achieved in 23 pigs. Sensed signals were analyzed and stored as real-time audio/video feedback EMG system. RLN was stressed by mechanical and thermal injury; signal alterations were evaluated. RESULTS: VNs were successfully real-time stimulated by using the anchor electrode. No complications or side effects during stimulation were detected. RLN injury led to an alteration of signal amplitude and latency period but signal restitution after injury. CONCLUSIONS: Real-time monitoring of the RLN is technically feasible to perceive imminent nerve failure. The anchor electrode was safely and easy to handle. Its implementation is being tested in an ongoing clinical trial. PMID- 20359571 TI - Cyclosporine A--protection against microvascular hyperpermeability is calcineurin independent. AB - BACKGROUND: Mitochondria-mediated apoptotic signaling contributes to microvascular hyperpermeability. We hypothesized that cyclosporine A (CsA), which protects mitochondrial transition pores, would attenuate hyperpermeability independent of its calcineurin inhibitory property. METHODS: Hyperpermeability was induced in microvascular endothelial cell monolayers using proapoptotic BAK or active caspase-3 after CsA or a specific calcineurin inhibitor, calcineurin autoinhibitory peptide (CIP), treatment. Permeability was measured based on fluorescein isothiocyanate-albumin flux across the monolayers. Mitochondrial transmembrane potential (MTP) was determined using 5,5',6,6'-tetrachoro-1,1',3,3' tetraethylbenzimidazolyl carbocyanine iodide. Mitochondrial release of cytochrome c was measured using an enzyme-linked immunosorbent assay and caspase-3 activity fluorometrically. RESULTS: CsA-attenuated (10 nmol/L) but not CIP-attenuated (100 mumol/L) BAK induced hyperpermeability (P < .05), CsA- but not CIP-attenuated BAK induced a decrease in MTP and an increase in cytochrome c levels and caspase-3 activity (P < .05). CsA and CIP were ineffective against caspase-3-induced hyperpermeability. CONCLUSIONS: CsA attenuated hyperpermeability by protecting MTP, thus preventing mitochondria-mediated apoptotic signaling. The protective effect of CsA is independent of calcineurin inhibition. PMID- 20359572 TI - Disparity in limb-salvage surgery among sarcoma patients. AB - BACKGROUND: Recent studies have shown that aggressive preoperative radiation increases the likelihood of limb salvage in sarcoma patients. METHOD: The Surveillance, Epidemiology and End Results database was used to run an adjusted logistic regression for the receipt of cancer-directed treatment modalities. RESULTS: Of patients with specific surgical procedures recorded (n = 2,104), 86.0% had undergone a limb-sparing procedure. On bivariate analysis, African American patients were less likely to receive a limb-sparing procedure than white patients (80.4% vs 86.9%; P = .02). On multivariate analysis, African Americans were significantly more likely to receive preoperative radiation (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.22-4.40; P = .011), yet this did not translate into an increase in limb salvage (OR, .67; 95% CI, .42-1.08; P = .10). Limb salvage significantly increased for all groups in 2001 and after (OR, 2.75; 95% CI, 1.55-4.88; P = .001) without a decrease in survival. For those with tumors greater than 4 cm, there was a trend away from limb salvage for African Americans (OR, .59; 95% CI, .32-1.07; P = .08). CONCLUSIONS: Our results of an increase in limb-salvage surgeries after 2001 without a decrease in survival support previous studies. The trend away from limb salvage for African Americans cannot be answered by this study. PMID- 20359573 TI - Insurance status is a potent predictor of outcomes in both blunt and penetrating trauma. AB - BACKGROUND: Patients with penetrating injuries are known to have worse outcomes than those with blunt trauma. We hypothesize that within each injury mechanism there should be no outcome difference between insured and uninsured patients. METHODS: The National Trauma Data Bank version 7 was analyzed. Patients aged 65 years and older and burn patients were excluded. The insurance status was categorized as insured (private, government/military, or Medicaid) and uninsured. Multivariate analysis adjusted for insurance status, mechanism of injury, age, race, sex, injury severity score, shock, head injury, extremity injury, teaching hospital status, and year. RESULTS: A total of 1,203,243 patients were analyzed, with a mortality rate of 3.7%. The death rate was significantly higher in penetrating trauma patients versus blunt trauma patients (7.9% vs 3.0%; P < .001), and higher in the uninsured (5.3% vs 3.2%; P < .001). On multivariate analysis, uninsured patients had an increased odds of death than insured patients, in both penetrating and blunt trauma patients. Penetrating trauma patients with insurance still had a greater risk of death than blunt trauma patients without insurance. CONCLUSIONS: Insurance status is a potent predictor of outcome in both penetrating and blunt trauma. PMID- 20359574 TI - Age is a strong risk factor for atrial fibrillation after pulmonary lobectomy. AB - BACKGROUND: Atrial fibrillation (AF) after pulmonary lobectomy can be associated with increased morbidity and mortality as well as increased costs. METHODS: The records of 360 patients who underwent lobectomy between 2004 and 2008 at a single institution were reviewed. Univariate and multivariate analyses were performed to identify whether any recorded parameters served as prognostic variables in the development of AF. RESULTS: The overall incidence of AF was 18% (65 of 360). Univariate/multivariate analyses showed that age and preoperative history of AF/antiarrhythmic medications were strongly predictive for the development of AF (P < or = .001). CONCLUSIONS: Age and pre-existing cardiac disease/arrhythmias are strong risk factors for AF after pulmonary lobectomy by both univariate and multivariate analyses. This study suggests that the elderly are at increased risk for AF. Therefore, this population should be monitored closely or targeted for prophylactic therapy. PMID- 20359575 TI - Residents' self-reported learning needs for intraoperative knowledge: are we missing the bar? AB - BACKGROUND: The purpose of this study was to compare the intraoperative learning needs and educational resource use of junior and senior residents. Our goal was to gain a better understanding of the progression of learning needs in surgical training. METHODS: Residents (n = 125) completed a previously validated, 27-item survey indicating the following: (1) the extent to which traditional learning resources are used when preparing for cases in the operating room, and (2) which intraoperative management topics in which they believed they were deficient despite preoperative preparation. RESULTS: On a scale of 1 to 5, with 5 indicating frequent use, postgraduate year (PGY)-5 residents (n = 39) indicated surgical atlases (4.15; SD, .90) and surgical texts (4.15; SD, .90) were their most frequently used resources when preparing for a case in the operating room. In contrast, PGY-1 residents (n = 32) indicated anatomy atlases (3.97; SD, .93) and advice from colleagues (3.64; SD, .90) were their most frequently used resources when preparing for a case in the operating room. Despite the differences in how the PGY-5 group and the PGY-1 group prepared for a case, of 12 intraoperative management topics both groups believed they were the least prepared for instrument use/selection and suture selection. CONCLUSIONS: Today's residents represent a heterogeneous group of individuals with different learning needs based on level of experience, knowledge, and learning style. Our study highlights unexpected but critical learning needs for senior-level residents that can and should be readily addressed. PMID- 20359576 TI - Ureteral trauma: patterns and mechanisms of injury of an uncommon condition. AB - BACKGROUND: Traumatic ureteral injuries are uncommon, thus large series are lacking. METHODS: We performed a retrospective analysis of the National Trauma Data Bank (2002-2006). RESULTS: Of the 22,706 genitourinary injuries, 582 ureteral injury patients were identified (38.5% blunt, 61.5% penetrating). Patients were 84% male, 38% white, and 37% black (mean age, 31 y). Blunt trauma patients had a median Injury Severity Score of 21.5 versus 16.0 for penetrating injury (P < .001). Mortality rates were 9% blunt, and 6% penetrating (P = .166). Penetrating trauma patients had a higher incidence of bowel injuries (small bowel, 46%; large bowel, 44%) and vascular injuries (38%), whereas blunt trauma patients had a higher incidence of bony pelvic injuries (20%) (P < .001). CONCLUSIONS: Ureteral injuries are uncommon, seen in approximately 3 per 10,000 trauma admissions, and occur more in penetrating than in blunt trauma. The most common associated injury for blunt ureteral trauma is pelvic bone fracture, whereas penetrating ureteral trauma patients have more hollow viscus and vascular injuries. PMID- 20359577 TI - Editorial comment: regarding "Moral angst for surgical residents: a qualitative study". PMID- 20359578 TI - Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy. AB - Current therapeutic design involves combinatorial chemistry and system biology based molecular synthesis and bulk pharmacological assays. Therapeutics delivery is usually non-specific to disease targets and requires excessive dosage. Efficient therapeutic discovery and delivery would require molecular level understanding of the therapeutics-effectors (e.g., channels and receptors) interactions and their cell and tissue responses. This review summarizes the application of multidimensional scanning probe techniques, especially atomic force microscopy (AFM), for drug discovery. Important features of AFM include its capability of atomic scale structural and physical properties study of live biological systems, its open architecture that allows its integration with other techniques, tools and operating environments, and its application for creating and characterizing nanocarriers and implantable vehicles for controlled delivery. Specific areas covered include: 1) the operating principle and examples of AFM integrated with electrical recording, fluorescence imaging and microfluidics, (2) examples of AFM nanoscale imaging that has provided new paradigms in pathogenesis, including protein misfolding diseases (e.g., Alzheimer's disease, cancer, diabetes) and diseases arising from environmental and life choices and thus identifies potential therapeutic targets, (3) high-throughput parallel sensors, comprising integrated cantilevered microarrays, TIRF, microfluidics and nanoelectronics, for potential rapid diagnosis of pathogens, allergens and biomarkers as well as for therapeutics design, (4) the definition target macromolecules and structures, using intermolecular interaction assays, (5) the definition of abnormal vs normal tissues and the assessment of therapeutic efficacy by monitoring biomechanics, and (6) the development and characterization of nanocarrier-based drug delivery (e.g., nanoliposomes and nanoparticles) systems that allow high efficiency in vivo or the topical administration of a small dosage of therapeutics. PMID- 20359579 TI - Functional classification of peripheral T-cell lymphomas as an approach to improve outcome prediction and therapy selection. AB - Many types of peripheral T-cell lymphoma (PTCL) are currently classified by the World Health Organization (WHO) based on their predominant site of organ involvement (eg, intestinal or cutaneous types). However, this approach and traditional staging scores such as the IPI can provide limited prognostic information, especially in those PTCL types where morbidity and mortality are primarily related to immune dysregulation and cytokine syndromes driven by the lymphoma cells. These "immune participatory" PTCLs (including, commonly, angioimmunoblastic T-cell lymphoma and many extranodal types) can therefore have poor outcomes even at low tumor burdens. For these reasons, a classification that includes functional profiling of the lymphoma cells may add valuable prognostic information. Such data, including cytokine expression patterns and T-cell receptor signaling pathway activation status, whether normal or abnormal, need to be considered in future classification systems, especially when incorpating targeted therapy. PMID- 20359580 TI - Novel agents in development for peripheral T-cell lymphoma. AB - Though peripheral T-cell lymphoma (PTCL) is an area of significant unmet therapeutic need, a number of new treatment options are available for patients, especially those with relapsed or refractory disease. A plethora of drugs are now in development for PTCL, but drugs that truly target novel disease biology are noticeably absent. Combinations of T-cell centric agents could produce novel platforms of therapy to replace the relatively ineffective CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based regimens. Among agents with T-cell activity are the folate analog pralatrexate, histone deacetylase inhibitors (HDACi) like romidepsin, the proteasome inhibitor bortezomib, the immunomodulatory agent lenalidomide, the purine nucleoside phosphorylase (PNP) inhibitor forodesine, the nucleoside analog gemcitabine, and BH3-only mimetics like ABT-263 and ABT-737. PMID- 20359581 TI - High-dose therapy and stem cell transplantation. AB - Results of conventional or high-dose chemotherapy for peripheral T-cell lymphoma (PTCL) are unsatisfactory, leaving a potential role for autologous or allogeneic stem cell transplantation. There are a number of retrospective studies and a few prospective studies on autologous transplantation for first-line PTCL treatment. Studies show that autologous transplant is feasible in relapsed and previously untreated patients, and efficacy is comparable to results in aggressive B-cell lymphomas. Allogeneic transplant may also have a role in relapsed PTCL, especially in the context of reduced-intensity conditioning, which has decreased nonrelapse mortality. However, it is unclear whether there is a role for allogeneic transplant as a frontline treatment option. PMID- 20359582 TI - Status of ongoing collaborative efforts. AB - T-cell lymphomas are the rarest of all non-Hodgkin lymphomas (NHLs) and may therefore be the least understood. The aim of the T-Cell Project is to pool prospective data from centers around the world to improve understanding of the more frequent and the uncommon subtypes of T-cell lymphomas. To be eligible for enrollment in this study, patients must have previously untreated, de novo peripheral T-cell lymphoma (PTCL) or natural killer (NK)/T-cell lymphoma and be at least 18 years of age. As of October 2009, 479 patients from 13 centers were enrolled, and 454 of these cases were validated. The patients are evaluated for their responses to treatment, progression-free and overall survival, and treatments received. PMID- 20359583 TI - Clinical trials for human T-cell lymphotropic virus type I-associated peripheral T-cell lymphoma in Japan. AB - The most common subtype of T-/natural killer (NK) cell lymphoma in Japan is adult T-cell leukemia-lymphoma (ATL), which is associated with the human T-cell lymphotropic virus type I (HTLV-1). The investigators in Japan have conducted several clinical trials on multi-agent chemotherapy and stem cell transplantation for patients with ATL. They have also initiated several new clinical trials with a number of agents: an anti-CCR4 antibody, KW-0761; forodesine, a purine nucleoside phosphorylase inhibitor; and lenalidomide, an immunomodulatory agent. Clinical trials with pralatrexate, a folate analog, and denileukin diftitox, an immunoconjugate, are under discussion for patients with ATL and peripheral T-cell lymphoma (PTCL). PMID- 20359584 TI - Enhancing existing approaches to peripheral T-cell lymphoma. AB - The National Comprehensive Cancer Network (NCCN) practice guidelines for peripheral T-cell lymphoma (PTCL) accentuate the lack of standard treatment options for this disease. Outcomes with conventional therapies, many of which are borrowed from B-cell lymphoma, are poor. Strategies to enhance existing approaches include creating a new platform for first-line therapy and adding novel agents, such as denileukin diftitox, to existing chemotherapy platforms. Furthermore, to improve outcomes, patients must reach transplant through effective first-line therapies. Additionally, treatment should be individualized based on histopathologic subtype, as all PTCL patients will not respond to the same treatment regimen. PMID- 20359586 TI - Cognitive activation theory of stress (CATS). AB - The cognitive activation theory of stress (CATS) is based on a long series of experiments on animals and on humans, in the laboratory, and in real life situations. From the common sense coping concept formulated by Seymour Levine; coping is when my "tommy" does not hurt, we have advanced to a systematic theory for what is behind the relaxed and happy coping rat (and cat). We also cover the translational leap to humans, starting with the now classic parachutist study. The bridge is based on formal and symbolic definitions, a theoretical short cut that Levine actually never really accepted. The essential pathophysiological concept is the potential pathological effects of sustained activation, which may occur in the absence of coping (positive response outcome expectancy). We review the current status of CATS in Behavioural Medicine by discussing its potential explanatory power in epidemiology, prevention and treatment of "subjective health complaints". PMID- 20359585 TI - Early attachment-figure separation and increased risk for later depression: potential mediation by proinflammatory processes. AB - Early maternal separation and other disruptions of attachment relations are known to increase risk for the later onset of depressive illness in vulnerable individuals. It is suggested here that sensitization involving proinflammatory processes may contribute to this effect. This argument is based on: (1) current notions of the role of proinflammatory cytokines in depressive illness; (2) evidence that proinflammatory cytokines mediate depressive-like behavior during separation in a rodent model of infant attachment; and (3) comparisons of the effects of early proinflammatory activation versus maternal separation on later proinflammatory activity and biobehavioral processes related to depression. The possible interaction of proinflammatory processes and corticotropin-releasing factor in the sensitization process is discussed. PMID- 20359587 TI - Significant aortic coarctation presenting as subarachnoid hemorrhage in the adult. PMID- 20359588 TI - 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology,American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons,and Society for Vascular Medicine. PMID- 20359589 TI - Acute coronary syndrome: emerging tools for diagnosis and risk assessment. AB - Acute coronary syndrome encompasses a broad and heterogeneous population that challenges the clinician at each step of treatment in terms of: 1) diagnosis; 2) appropriate risk stratification; 3) therapeutic decision making; and 4) monitoring response to therapy. Although there are many established tools for diagnosis, prognosis, and clinical decision making, understanding the advantages and limitations of each tool according the clinical scenario is essential. Several emerging tools, such as novel biomarkers (e.g., high-sensitivity troponin and growth differential factor-15), ECG techniques (e.g., heart rate turbulence or T-wave alternans), and imaging modalities (computed tomography angiography and cardiac magnetic resonance) may potentially improve clinical care; however, they must be fully evaluated and validated in different scenarios and patient cohorts before they are incorporated into clinical practice. This review identifies promising new or emerging techniques, as well as established tools, and reviews their current or potential role in clinical practice. PMID- 20359590 TI - Impact of delay to angioplasty in patients with acute coronary syndromes undergoing invasive management: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. AB - OBJECTIVES: The aim of this study was to determine the impact of delay to angioplasty in patients with acute coronary syndromes (ACS). BACKGROUND: There is a paucity of data on the impact of delays to percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) undergoing an invasive management strategy. METHODS: Patients undergoing PCI in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial were stratified according to timing of PCI after clinical presentation for outcome analysis. RESULTS: Percutaneous coronary intervention was performed in 7,749 patients (median age 63 years; 73% male) with NSTE-ACS at a median of 19.5 h after presentation (<8 h [n=2,197], 8 to 24 h [n=2,740], and >24 h [n=2,812]). Delay to PCI>24 h after clinical presentation was significantly associated with increased 30-day mortality, myocardial infarction (MI), and composite ischemia (death, MI, and unplanned revascularization). By multivariable analysis, delay to PCI of >24 h was a significant independent predictor of 30-day and 1-year mortality. The incremental risk of death attributable to PCI delay>24 h was greatest in those patients presenting with high-risk features. CONCLUSIONS: In this large-scale study, delaying revascularization with PCI>24 h in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes. These findings suggest that urgent angiography and triage to revascularization should be a priority in NSTE-ACS patients. PMID- 20359591 TI - Do not put off until tomorrow what you can do today. PMID- 20359592 TI - Pre-procedural glucose levels and the risk for contrast-induced acute kidney injury in patients undergoing coronary angiography. AB - OBJECTIVES: We sought to evaluate whether pre-procedural glucose levels are associated with contrast-induced acute kidney injury (CI-AKI) after coronary angiography. BACKGROUND: Although diabetes is a known risk factor for CI-AKI in patients undergoing coronary angiography, whether elevated pre-procedural glucose levels (regardless of pre-existing diabetes) are associated with higher risk for CI-AKI is unknown. METHODS: We evaluated 6,358 patients with acute myocardial infarctions undergoing coronary angiography. Patients were stratified into 5 pre procedural glucose groups: <110 mg/dl, 110 to <140 mg/dl, 140 to <170 mg/dl, 170 to <200 mg/dl, and >or=200 mg/dl. Logistic regression models were used to evaluate the relationship between glucose levels and risk for CI-AKI, first in the entire cohort and then in patients with and without established diabetes. The primary outcome was CI-AKI (>or=0.3 mg/dl absolute or >or=50% relative serum creatinine increase during 48 h after the procedure). RESULTS: The relationship between pre-procedural glucose and CI-AKI varied markedly in patients with and without diabetes. There was a strong association between glucose and CI-AKI risk in patients without diabetes (CI-AKI rates across the 5 glucose groups from lowest to highest: 8.2%, 9.9%, 12.4%, 14.9%, and 24.3%; p<0.001), but not in patients with diabetes (20.9%, 16.1%, 16.3%, 14.8%, and 19.2%, respectively; p=0.24; p for glucose x diabetes interaction<0.001). After adjusting for confounders (including baseline glomerular filtration rate), the relationship between higher glucose and greater CI-AKI risk persisted in patients without diabetes (odds ratios [95% confidence intervals] for glucose groups of 110 to <140 mg/dl, 140 to <170, mg/dl 170 to <200 mg/dl, and >or=200 mg/dl: 1.31 [1.00 to 1.71], 1.51 [1.11 to 2.10], 1.58 [1.03 to 2.43], and 2.14 [1.46 to 3.14] vs. glucose<110 mg/dl, respectively), but this relationship was not seen in patients with established diabetes. CONCLUSIONS: Elevated pre-procedural glucose is associated with greater risk for CI-AKI in patients without known diabetes who undergo coronary angiography in the setting of acute myocardial infarction. Measures used to prevent CI-AKI should be considered in these patients. PMID- 20359593 TI - Pre-procedural blood glucose levels: a new risk marker for contrast-induced acute kidney injury in patients without diabetes with acute myocardial infarction. PMID- 20359595 TI - A glimpse into multigene rare variant genetics: triple mutations in hypertrophic cardiomyopathy. PMID- 20359594 TI - Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations. AB - OBJECTIVES: The aim of this study was to describe the clinical profile associated with triple sarcomere gene mutations in a large hypertrophic cardiomyopathy (HCM) cohort. BACKGROUND: In patients with HCM, double or compound sarcomere gene mutation heterozygosity might be associated with earlier disease onset and more severe outcome. The occurrence of triple mutations has not been reported. METHODS: A total of 488 unrelated index HCM patients underwent screening for myofilament gene mutations by direct deoxyribonucleic acid sequencing of 8 genes, including myosin binding protein C (MYBPC3), beta-myosin heavy chain (MYH7), regulatory and essential light chains (MYL2, MYL3), troponin-T (TNNT2), troponin I (TNNI3), alpha-tropomyosin (TPM1), and actin (ACTC). RESULTS: Of the 488 index patients, 4 (0.8%) harbored triple mutations, as follows: MYH7-R869H, MYBPC3 E258K, and TNNI3-A86fs in a 32-year-old woman; MYH7-R723C, MYH7-E1455X, and MYBPC3-E165D in a 46-year old man; MYH7-R869H, MYBPC3-K1065fs, and MYBPC3-P371R in a 45-year old woman; and MYH7-R1079Q, MYBPC3-Q969X, and MYBPC3-R668H in a 50 year old woman. One had a history of resuscitated cardiac arrest, and 3 had significant risk factors for sudden cardiac death, prompting the insertion of an implantable cardioverter-defibrillator in all, with appropriate shocks in 2 patients. Moreover, 3 of 4 patients had a severe phenotype with progression to end-stage HCM by the fourth decade, requiring cardiac transplantation (n=1) or biventricular pacing (n=2). The fourth patient, however, had clinically mild disease. CONCLUSIONS: Hypertrophic cardiomyopathy caused by triple sarcomere gene mutations was rare but conferred a remarkably increased risk of end-stage progression and ventricular arrhythmias, supporting an association between multiple sarcomere defects and adverse outcome. Comprehensive genetic testing might provide important insights to risk stratification and potentially indicate the need for differential surveillance strategies based on genotype. PMID- 20359596 TI - Pharmacokinetic and hemodynamic responses to oral sildenafil during invasive testing in children with pulmonary hypertension. AB - OBJECTIVES: The purpose of our study was to characterize the hemodynamic and corresponding pharmacokinetic responses to a single dose of oral sildenafil by children with pulmonary arterial hypertension (PAH) undergoing invasive testing. BACKGROUND: Although used frequently for the treatment of children with PAH, data regarding the acute responses to sildenafil are limited. METHODS: Thirty-six patients (mean age 7.5+/-5.9 years; 24 females) were studied during cardiac catheterization with general anesthesia. Eight of 36 (22%) had idiopathic PAH; the remainder had associated congenital heart disease. Hemodynamics and serum cyclic-guanosine monophosphate levels (cGMP) were evaluated at baseline and after inhaled nitric oxide (NO) (40 ppm). In addition, cGMP and sildenafil levels were measured 30 min after administration of sildenafil (0.5 mg/kg, suspended in 5 ml sterile water) through a nasogastric tube. RESULTS: For the 36 patients, the pulmonary vasodilating capability of oral sildenafil was lower than that of inhaled NO (2.8% vs. 11.6% reduction in pulmonary vascular resistance indexed to body surface area [PVRI], respectively; p=0.01). However, only 21 of 36 (58%) patients had a detectable sildenafil level. In those with detectable sildenafil levels, the fall in PVRI was greater (-11.6% vs. -19.1%, p=NS). Mean cGMP levels at baseline and after NO were 41.8+/-20.0 pmol/ml and 83.8+/-35.5 pmol/ml, respectively (p<0.0001). Surprisingly, there was no significant increase in cGMP in patients with either undetectable (37.5+/-29.8 pmol/ml) or detectable (44.4+/ 31.7 pmol/ml) sildenafil levels (p=NS compared with baseline) with sildenafil. CONCLUSIONS: Our study demonstrates suboptimal absorption of sildenafil in almost half the children undergoing acute hemodynamic testing. When detectable, there was no statistically significant difference between the fall in PVRI associated with sildenafil and NO despite lower circulating cGMP levels in the sildenafil group. These data should be taken into account when designing acute testing protocols, and assessing the acute response to sildenafil in patients with PAH. PMID- 20359597 TI - Common functional genetic variants in catecholamine storage vesicle protein promoter motifs interact to trigger systemic hypertension. AB - OBJECTIVES: The purpose of this study is to understand whether naturally occurring genetic variation in the promoter of chromogranin B (CHGB), a major constituent of catecholamine storage vesicles, is functional and confers risk for cardiovascular disease. BACKGROUND: CHGB plays a necessary (catalytic) role in catecholamine storage vesicle biogenesis. Previously, we found that genetic variation at CHGB influenced autonomic function, with association maximal toward the 5' region. METHODS: Here we explored transcriptional mechanisms of such effects, characterizing 2 common variants in the proximal promoter, A-296C and A 261T, using transfection/cotransfection, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP). We then tested the effects of promoter variation on cardiovascular traits. RESULTS: The A-296C disrupted a c FOS motif, exhibiting differential mobility shifting to chromaffin cell nuclear proteins during EMSA, binding of endogenous c-FOS on ChIP, and differential response to exogenous c-FOS. The A-261T disrupted motifs for SRY and YY1, with similar consequences for EMSA, endogenous factor binding, and responses to exogenous factors. The 2-SNP CHGB promoter haplotypes had a profound (p=3.16E-20) effect on blood pressure (BP) in the European ancestry population, with a rank order of CT43 mmHg) were independently associated with a lower chance of survival. CONCLUSION: CPET with blood gas analysis may have a prognostic value in adult CF patients. Further larger prospective clinical studies are warranted to confirm these preliminary results. PMID- 20359614 TI - [Smoking and educational status in Africans]. AB - INTRODUCTION: Tobacco smoking is a scourge that continues to increase in developing countries despite its known consequences. Is the population of the Ivory Coast sufficiently informed about the consequences of smoking? For this reason, we decided to evaluate the knowledge of the effects of smoking among the people of Abidjan. OBJECTIVE: To evaluate the knowledge of the effects of smoking in the population of Abidjan. To relate this knowledge to the educational level and smoking status. METHODS: We evaluated knowledge about smoking and its consequences as a function of educational level and smoking status in the population of Abidjan over the age of 15 years. This was undertaken in 3 months, from November 2005 to January 2006, in the two busiest communes in Abidjan. The minimum number of persons required was 1152 but, in fact, we interviewed 1409. RESULTS: The prevalence of smoking was 36.5% with a predominance of males (sex ratio = 3:11). They were mainly young with a mean age of 27.44 years. This population's main sources of information on the ill effects of smoking were the mass media. In general, the subjects did not have a good understanding of smoking and its consequences. With regard to the diseases related to smoking, bronchial carcinoma and cardiovascular disorders were the best known, in 53.1 and 18.1%, respectively. With regard to the components of tobacco, nicotine was the best known (92.6%). Knowledge was related to the level of education: the subjects of a higher educational level were the most knowledgeable about the consequences of smoking. As a result, these subjects were less attached to smoking than the less educated. CONCLUSION: The consequences of smoking are poorly understood by the general population. With regard to the level of education, the better educated had a better understanding of the effects of smoking and were also those who smoked the least. PMID- 20359615 TI - [Interstitial lung disease and anti-TNF-alpha therapy in rheumatoid arthritis: Two different patterns?]. AB - The first lung complications of anti-TNF-alpha therapy in rheumatoid arthritis (RA) that were reported were infections. Recently, interstitial lung disease (ILD) has been described as a consequence of this treatment. We report two cases of women treated with anti-TNF-alpha therapy for RA who both developed exacerbations of their preexisting ILD thought to be due to the treatment. In one case, this complication occurred 2 months after anti-TNF-alpha therapy, whereas the delay of occurrence was 26 months in the second case. Based on these two cases and on the first 40 observations in the literature, we hypothesize that ILD may be exacerbated according to two distinct patterns during anti-TNF-alpha treatment for RA, occurring early (most frequently) or late after treatment was started, with a mean of 4 and 26 months, respectively. Other features that may differ between these two presentations include the risk factors, the anti-TNF alpha molecule used, the histopathological pattern, and the prognosis. PMID- 20359616 TI - [Clinical study of interstitial lung disease in mixed connective tissue disease]. AB - Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis/dermatomyositis, with a high anti-snRNP antibody titer. Respiratory manifestations, such as interstitial lung disease (ILD), are not well-described. Thirteen patients who met the diagnostic criteria for MCTD and showed ILD on high-resolution CT were analysed retrospectively. A restrictive pattern was found in 73% of cases and TLCO abnormalities in 90%. Exercise hypoxemia was observed in nine out of ten cases. The CT-scan pattern was compatible with non-specific interstitial pneumonia in seven cases and with usual interstitial pneumonia in five. Bronchoalveolar lavage showed lymphocytic alveolitis in two patients, neutrophil alveolitis in eight. Fifty percent ILD patients respond to steroids and immunosuppressive drugs. Progressive ILD (six in 13; 46%) compared with non-progressive ILD associated more systemic sclerosis manifestations (p<0.05). Progressive ILD tend to have more frequent pulmonary hypertension, neutrophilic alveolitis and honey combing pattern. MCTD-ILD characteristics are not specific. When systemic sclerosis manifestations are present, MCTD-ILD seems to associate more frequently pulmonary hypertension and progressive ILD. PMID- 20359617 TI - [Lyell's syndrome occurring in three HIV-positive patients undergoing anti tuberculous therapy]. AB - We describe three cases of Lyell syndrome - toxic epidermal necrolysis - occurring in patients under the respiratory service of CHU de Cocody in Abidjan in the Ivory Coast, who were undergoing anti-tuberculous (TB) chemotherapy. All three were adult males who were HIV-positive, but none of them were receiving anti-retroviral treatment. They were on standard anti-TB treatment; rifampicin, isoniazid, pyazinamide and ethambutol. The lesions appeared early during their treatment for TB (14, 20 and 45 days). The patients were on no other medication that might have caused Lyell's syndrome except one who had been on cotrimoxasole for 6 months without complications. Despite admission to the acute care facility and appropriate care two of the three patients died. PMID- 20359618 TI - [Paraneoplastic sclerodermiform syndrome]. AB - INTRODUCTION: Despite the known association between scleroderma and cancer, the current systemic sclerosis classifications do not clearly identify paraneoplastic sclerodermiform syndrome or sclerodermiform syndrome secondary to cancer treatments. CASE REPORT: A 56 year old man was hospitalized for severe Raynaud's phenomenon with bilateral digital necrosis and otherwise good health status. X rays did not show any subcutaneous calcification. Levels of serum antinuclear antibodies were high but anticentromere and anti-topoisomerase 1 antibodies were negative. Chest X-ray and CT-scan identified an irregular opacity in the right upper lobe with enlarged mediastinal lymph nodes. A diagnosis of bronchial adenocarcinoma was made following mediastinoscopy and the patient was treated with neo-adjuvant chemotherapy and lobectomy. After two cycles of treatment, his skin lesions had almost disappeared. CONCLUSION: The presence of a sclerodermiform syndrome may suggest the existence of an underlying neoplasm. In this case report, the skin lesions disappeared quickly after antineoplastic treatment. We suggest that sclerodermiform syndrome be included in the systemic sclerosis classification. PMID- 20359619 TI - [Pancytopenia in disseminated tuberculosis: Think of macrophage activation syndrome]. AB - INTRODUCTION: The macrophage activation syndrome (MAS), also known as haemophagacytosis, is a non-specific clinical syndrome, which includes, among other things general debility, fever and hepatospleneomegaly. The most frequent pathological abnormalities are pancytopenia, hypertryglyceraemia, and hyperferrititinaemia. These clinical and biological criteria, which determine the severity of MAS, must be associated with a histological criterion - haemophagocytosis (with histiocytosis), which is usually medullary but can more rarely be splenic, hepatic or ganglionic. MAS can be primary or secondary. In the latter case, it is frequently associated with an infection of which tuberculosis is the most common. OBSERVATION: We describe the case of a young immunocompetent patient who had disseminated tuberculosis complicated by MAS. CONCLUSION: It is important to be aware of MAS, because its occurrence is associated with a poor prognosis and its optimal treatment, which requires a multidisciplinary approach, has not been fully defined. The optimum strategy in relation to specific aetiologies remains to be clarified. PMID- 20359620 TI - [Small cell lung cancer and anti-Hu syndrome]. AB - INTRODUCTION: The anti-Hu associated syndrome is a rare paraneoplastic neurological syndrome, which is principally associated with small-cell lung cancer. OBSERVATION: We report the case of a patient with the following clinical features: dysautonomia with severe gastroparesis, sensory neuropathy and a rhombencephalitis. Tumour regression was obtained with chemotherapy but the patient ultimately died from the neurological complications. CONCLUSION: Neurological syndromes associated in small cell lung cancer with anti-Hu antibodies are very diverse. Cancer evolution is generally speaking more benign than usual with the prognosis linked to the severity of the neurological involvement. PMID- 20359621 TI - [Evaluation of the deficiency and the submaximal exercise capacity in obstructive sleep apnoea patients]. AB - BACKGROUND: In addition to excessive daytime somnolence, exercise limitation is a likely consequence of the cardiorespiratory problems that occur in patients who have obstructive sleep apnoea (OSA). However, few studies have evaluated the aerobic capacity of this patient group. AIMS: To evaluate submaximal exercise capacity over the 6-minute walking test (6-MWT). To determine the factors that influence 6-minutes walking distance (6-MWD). METHODS: INCLUSION CRITERIA: 120 consecutive patients with severe OSA treated by continuous positive airway pressure who were medically stable will be included. EXCLUSION CRITERIA: 6-MWT contraindications, orthopaedic or rheumatologic diseases likely to influence walking capacity and corticosteroid therapy. INVESTIGATIONS: polysomnography, electrocardiogram, plethysmography, and two 6-MWT's. Indicators of impaired exercise capacity: stops during the walk, 6-MWD less than or equal to predicted lower limit of normal, end walking dyspnoea greater than or equal to 5/10, oxygen saturation fall greater than or equal to five points, end walking heart rate less than or equal to 60 % maximal predicted. Data from our obese patients aged 40-60 years old will be compared with data from 45 age-matched obese subjects free from OSA. EXPECTED RESULTS: OSA will significantly affect the submaximal exercise capacity and will accelerate the ageing of the cardiorespiratory-muscle chain. Submaximal exercise capacity of obese subjects having OSA, compared to subjects free from OSA, will be significantly deteriorated. 6-MWD of OSA patients will be significantly influenced by: resting plethysmographic data, apnoea hypopnoea index, arterial hypertension, obesity or smoking histories. PMID- 20359622 TI - [About multiple extrapulmonary thoracic hydatidosis]. PMID- 20359623 TI - [Master specialty, year 2, cardiovascular and respiratory biology, physiology and pharmacology, Option: "respiration"; a new quadrennial]. PMID- 20359624 TI - [Respiratory research conference 2009]. PMID- 20359625 TI - Preface. The biology and treatment of myelodysplastic syndrome. PMID- 20359627 TI - The genetic basis of myelodysplastic syndromes. AB - Myelodysplastic syndrome (MDS) disorders are clonal diseases that often carry stereotypic chromosomal abnormalities. A smaller proportion of cases harbor point mutations that activate oncogenes or inactivate tumor suppressor genes. New technologies have accelerated the pace of discovery and are responsible for the identification of novel genetic mutations associated with MDS and other myeloid neoplasms. These discoveries have identified novel mechanisms in the pathogenesis of MDS. This article touches on the better known genetic abnormalities in MDS and explains in greater detail those that have been discovered more recently. Understanding how mutations lead to MDS and how they might cooperate with each other has become more complicated as the number of MDS-associated genetic abnormalities has grown. In some cases, these mutations have prognostic significance that could improve upon the various prognostic scoring systems in common clinical use. PMID- 20359626 TI - The epidemiology of myelodysplastic syndromes. AB - The incidence of the myelodysplastic syndromes (MDS) in the United States is reported as 3.4 per 100,000 people, translating to over 10,000 new diagnoses annually. This figure is considered to be an underestimate as our data capture techniques improve, and probably translates to a prevalence of approximately 60,000 people or more living with the disease. Patients are in their seventh or eighth decades at diagnosis, typically present with cytopenias, and have substantive transfusion requirements. The most common risk factors for developing MDS include advanced age, male gender, previous exposure to chemotherapy or radiation therapy, smoking, or, in rare cases, exposure to industrial chemicals. PMID- 20359628 TI - Epigenetic changes in the myelodysplastic syndrome. AB - Epigenetic mechanisms, such as DNA methylation and histone modifications, drive stable, clonally propagated changes in gene expression and can therefore serve as molecular mediators of pathway dysfunction in neoplasia. Myelodysplastic syndrome (MDS) is characterized by frequent epigenetic abnormalities, including the hypermethylation of genes that control proliferation, adhesion, and other characteristic features of this leukemia. Aberrant DNA hypermethylation is associated with a poor prognosis in MDS that can be accounted for by more rapid progression to acute myeloid leukemia. In turn, treatment with drugs that modify epigenetic pathways (DNA methylation and histone deacetylation inhibitors) induces durable remissions and prolongs life in MDS, offering some hope and direction in the future management of this deadly disease. PMID- 20359629 TI - Immunosuppression for myelodysplastic syndrome: how bench to bedside to bench research led to success. AB - Laboratory evidence and clinical evidence suggest that some patients with myelodysplastic syndrome (MDS) have immunologically mediated disease. This article describes the laboratory evidence supporting a role for the immune system in the marrow failure of MDS and clinical trials using IST in these patients. PMID- 20359630 TI - Innate immune signaling in the myelodysplastic syndromes. AB - Myelodysplastic syndromes (MDS) are heterogeneous clonal hematologic malignancies characterized by cytopenias caused by ineffective hematopoiesis and propensity to progress to acute myeloid leukemia. Innate immunity provides immediate protection against pathogens by coordinating activation of signaling pathways in immune cells. Given the prominent role of the innate immune pathway in regulating hematopoiesis, it is not surprising that aberrant signaling of this pathway is associated with hematologic malignancies. Increased activation of the innate immune pathway may contribute to dysregulated hematopoiesis, dysplasia, and clonal expansion in myelodysplastic syndromes. PMID- 20359632 TI - Lenalidomide for treatment of myelodysplastic syndromes: current status and future directions. AB - Lenalidomide was approved by the US Food and Drug Administration (FDA) for treatment of transfusion-dependent lower-risk myelodysplastic syndrome patients with deletion (del) (5q) alone or with additional karyotype abnormalities. The approval was based on high rates of prolonged transfusion independence and complete cytogenetic response in this subset. In lower-risk non-del(5q) patients, meaningful erythroid responses also were reported with a low frequency of cytogenetic improvement, although inferior to that observed in the del(5q) patients. There is now a better understanding of the mechanism of the karyotype dependent drug action, explaining the disparate response rates and frequency of myelosuppression. In del(5q) patients, lenalidomide suppresses the clone by inhibiting the nuclear sequestration of the haplodeficient cell cycle regulatory protein cdc25c, thereby promoting selective G2 arrest and apoptosis. In non del(5q) patients, lenalidomide enhances erythropoietin receptor signaling. Future directions include use of biologic and molecular markers as predictive tools to select patients and use of combination strategies to overcome resistance to lenalidomide in del(5q) patients or enhance erythropoiesis in non-del 5 patients. PMID- 20359631 TI - Mouse models of myelodysplastic syndromes. AB - Three general approaches have been used to model myelodysplastic syndrome (MDS) in mice, including treatment with mutagens or carcinogens, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. This article discusses the phenotypes observed in available mouse models for MDS with a concentration on a model that leads to aberrant expression of conserved homeobox genes that are important regulators of normal hematopoiesis. Using these models of MDS should allow a more complete understanding of the disease process and provide a platform for preclinical testing of therapeutic approaches. PMID- 20359633 TI - Practical recommendations for hypomethylating agent therapy of patients with myelodysplastic syndromes. AB - Clinicians commonly administer one or the other of the two hypomethylating agents currently approved in the United States--azacitidine or decitabine--to patients with aggressive forms of myelodysplastic syndromes (MDS). However, there continues to be uncertainty about the optimal choice of agent, the best initial dose and treatment schedule, the role of hypomethylating agents in patients with more indolent disease, the most appropriate management of treatment-associated adverse events, and the most desirable approach to maintain responses. The evidence base supporting clinical decisions around these questions varies widely in depth and quality. This article discusses practical considerations for clinicians who use hypomethylating agents to treat patients with MDS. PMID- 20359635 TI - Novel therapies for myelodysplastic syndromes. AB - Preliminary therapeutic successes have prompted a new wave of clinical trials enrolling patients with myelodysplastic syndromes (MDS), using compounds with a broad range of potential mechanisms of action. This article discusses several of the agents currently in development for MDS, reviewing clinical trial data related to five classes of novel therapeutics: clofarabine, a halogenated purine nucleoside analog; ezatiostat (TLK199), a glutathione analog that indirectly activates c-Jun kinase; tipifarnib, a farnesyltransferase inhibitor; laromustine (cloretazine), an alkylating agent with a metabolite that inhibits one mechanism of DNA damage repair; and eight drugs that inhibit histone deacetylase. Although MDS are still difficult clinical problems, and most patients with MDS still succumb to disease-related complications within 3 to 5 years of diagnosis, ongoing development of novel agents promises that there will be new treatment options for patients within the next 5 to 10 years. PMID- 20359634 TI - Hematopoietic stem cell transplantation for MDS. AB - Hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for patients with myelodysplastic syndromes (MDS). However, as the majority of patients with MDS are in the seventh or eighth decade of life, conventional transplant regimens have been used only infrequently, and only with the development of reduced-intensity conditioning has transplantation been applied more broadly to older patients. Dependent upon disease status at the time of transplantation, 30% to 70% of patients can be expected to be cured of their disease and survive long term. However, posttransplant relapse and graft-versus host disease (GVHD) remain problems and further investigations are needed. PMID- 20359636 TI - Myelodysplastic syndromes classification and risk stratification. AB - Myelodysplastic syndromes (MDS) are spectrum of bone marrow failure disorders that share a common pathologic feature: cytologic dysplasia. The classification of MDS reflects the understanding of the disease. It is hoped that in the future classification and risk stratification will be based on underlying pathobiology of different disease subsets and molecular signatures where the pathologic classification represents their phenotype. This article reviews MDS classification and risk stratification highlighting differences between the various systems. PMID- 20359637 TI - Prognostic classification and risk assessment in myelodysplastic syndromes. AB - The clinical heterogeneity of myelodysplastic syndromes (MDS) is best illustrated by the observation that these disorders range from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia (AML). A risk-adapted treatment strategy is mandatory for conditions showing a highly variable clinical course, and definition of the individual risk has been based so far on the use of prognostic scoring systems. The authors have developed a prognostic model that accounts for the World Health Organization (WHO) categories, cytogenetics, transfusion dependency, and bone marrow fibrosis. This WHO classification-based Prognostic Scoring System (WPSS) is able to classify patients into five risk groups showing different survivals and probabilities of leukemic evolution. WPSS predicts survival and leukemia progression at any time during follow-up, and may therefore be used for implementing risk-adapted treatment strategies. PMID- 20359638 TI - Patient selection for transplantation in the myelodysplastic syndromes. AB - Allogeneic hematopoietic stem cell transplantation remains the only known curative procedure for the myelodysplastic syndromes (MDS). Because the median age at diagnosis for MDS is in the late seventh decade of life, despite the curative potential, transplantation is not undertaken routinely, and careful consideration must be made regarding the appropriateness of the transplant recipient. This article focuses on appropriate patient selection for transplantation for MDS. PMID- 20359639 TI - Writing, publishing, and the Journal. PMID- 20359640 TI - Information literacy for evidence-based practice in perianesthesia nurses: readiness for evidence-based practice. AB - Information literacy, the recognition of information required, and the development of skills for locating, evaluating, and effectively using relevant evidence is needed for evidence-based practice (EBP). The purpose of this study was to examine perianesthesia nurses' perception of searching skills and access to evidence sources. The design was a descriptive, exploratory survey. The sample consisted of ASPAN members (n = 64) and nonmembers (n = 64). The Information Literacy for Evidence-Based Nursing Practice instrument was used. Findings were that ASPAN members read more journal articles, were more proficient with computers, and used Cumulative Index to Nursing and Allied Health Literature (CINAHL) more frequently than nonmembers. The three top barriers to use of research were: lack of understanding of organization or structure of electronic databases, lack of skills to critique and/or synthesize the literature, and difficulty in accessing research materials. In conclusion, education is needed for critiquing literature and understanding electronic databases and research articles to promote EBP in perianesthesia areas. PMID- 20359641 TI - Temperature measurement in patients undergoing colorectal surgery and gynecology surgery: a comparison of esophageal core, temporal artery, and oral methods. AB - Maintaining perioperative normothermia reduces postoperative complications. An accurate, noninvasive method to take temperatures representative of core temperature is needed. Oral thermometry is accepted as the most accurate means of non-core temperature assessment, but poses challenges in patients who are intubated or wearing oxygen masks. The purpose of this study was to determine the difference, if any, between core temperature as measured by an esophageal thermometer and temperatures measured by oral and temporal artery methods in patients undergoing colorectal or gynecology surgery. A repeated-measures design was used with a convenience sample of 23 patients undergoing colorectal or gynecology surgery. Two series of intraoperative temperatures were taken (oral and temporal artery thermometry) and compared with core temperature measured by esophageal probe. Repeated-measures analysis of variance tested for biases of oral or temporal temperatures versus core temperatures. Bland-Altman plots were drawn to test dependence of bias on actual core temperature. A priori, a temperature difference >0.4 degrees C was defined as clinically significant. Oral temperature was biased high relative to esophageal temperature by 0.12 degrees C on average (P = .0008; 95% confidence interval [0.061, 0.187]). Temporal artery temperature was biased high relative to esophageal, by 0.074 degrees C on average (P = .03; 95% confidence interval [0.010, 0.133]). Differences between core (esophageal) thermometry and oral or temporal artery thermometry were statistically significant but much smaller than the 0.4 degrees C identified as clinically acceptable. Oral and temporal artery temperatures are within the 0.4 degrees C of core (esophageal) temperatures, a difference that is considered clinically acceptable. Temperatures taken orally or by temporal artery thermometry are acceptable as noninvasive core measures for adult patients undergoing colorectal or gynecology surgery. PMID- 20359642 TI - The impact of music on the PACU patient's perception of discomfort. AB - Pain is a normal finding in the postoperative patient, and noise can accentuate one's perception of discomfort. In this study, physiological measurements, intravenous (IV) opioid administration, length of stay, and satisfaction for postoperative patients who listened to music were compared with patients not provided music during their PACU stay. Of the 213 subjects enrolled, 163 experienced postoperative pain. The mean change in experimental subjects' respiratory rate was significantly lower than the controls. Decreases in heart rate and blood pressure from admission to discharge were similar between the two groups. On average, peripheral oxygen saturation and opioid pain control were not significantly different between control and experimental subjects. Subjects provided with music reported acceptable noise levels and increased satisfaction with their PACU experience. Music intervention is therefore a viable, minimal cost, and alternative therapy that PACU nurses can use to assist patients coping with postoperative pain. PMID- 20359643 TI - Comfort, satisfaction, and anxiolysis in surgical patients using a patient adjustable comfort warming system: a prospective randomized clinical trial. AB - Comfort warming systems aim to produce a comfortable local environment over which the individual patient has control. We studied a patient-adjustable comfort warming system using the Bair PAWS (Patient Adjustable Warming System) (Arizant Healthcare, Inc, Eden Prairie, MN), specifically to study comfort warming rather than therapeutic warming. One-hundred thirty patients were enrolled in this prospective randomized clinical trial, with 58 patients randomized to the patient warming gown, and 72 randomized to the warm blanket group. Groups were similar for gender, age, height, weight, surgical time, body surface area, and body mass index. The patient-adjustable warming system group had perceived greater control and satisfaction at 30 minutes after treatment was initiated compared with the warmed blanket control group. However, there were no differences in satisfaction levels with thermal comfort among those patients contacted one day postoperatively. Additional research is needed to improve external validity of study findings. Further refinement of a nursing definition of thermal comfort should be explored. PMID- 20359644 TI - Contrast media use in the operating room. AB - Iodinated contrast media is frequently used in the OR, but often is not well understood by health care providers who are administering it. Although used for diagnosis rather than treatment, contrast media is classified as a drug by the FDA, and has indications, contraindications, adverse effects, drug interactions, disease interactions, and laboratory interference issues related to its use. Iodinated contrast media is classified according to osmolarity and ionicity, and these characteristics contribute to potential for adverse effects and choice of agent. Financial and safety concerns are factors to be considered when selecting an appropriate agent. Adverse effects can range from mild and self-limited to severe and life threatening; potentially the most serious of these are anaphylactoid reactions and contrast-induced acute renal failure. Knowledge of risk factors and preventive strategies is vital, as are issues related to substitution of gadolinium-based contrast, an off-label use. It is important for the perianesthesia nurse to become familiar with these commonly used imaging medications. PMID- 20359645 TI - Pressure ulcer prevention: bringing it home to the perianesthesia world. PMID- 20359646 TI - Nursing informatics and ASPAN: clinical decision support through the perianesthesia data elements. PMID- 20359647 TI - Improving patient safety through quality indicators. PMID- 20359648 TI - The ICU patient. PMID- 20359649 TI - Pediatric patient safety: educating parents. PMID- 20359650 TI - Point: residual neuromuscular blockade in the PACU--a continuing serious problem. PMID- 20359651 TI - Counterpoint: Residual neuromuscular blockade in the PACU--a continuing serious problem. PMID- 20359653 TI - Notes from the 2009 American Society of Anesthesiologists' annual meeting. PMID- 20359654 TI - National Priorities Partnership: palliative and end-of-life care. PMID- 20359655 TI - Broaden the debate about assisted dying. PMID- 20359656 TI - 50 years of allogeneic bone-marrow transplantation. PMID- 20359657 TI - Molecular subtyping of breast cancer: ready to use? PMID- 20359658 TI - Metronomic chemotherapy for renal cancer in the landscape of targeted therapy. PMID- 20359659 TI - Do all patients with head and neck cancer benefit from radiotherapy and concurrent cetuximab? PMID- 20359660 TI - Cetuximab in metastatic colorectal cancer. PMID- 20359661 TI - In the interest of full disclosure. PMID- 20359664 TI - Molecular epidemiology and its current clinical use in cancer management. AB - The revelation of the entire human DNA sequence in 2001, and the launching of the international haplotype map (HapMap) project, made the identification of common markers of disease possible, dramatically transforming molecular epidemiology. In recent years, the development of, and discoveries within, human genome research have been rapid, highlighted by the current explosion of genome-wide association studies (GWAS). GWAS aim at finding germline changes that increase cancer risk. An equally important and rapid development had been seen in cancer genomics, with great strides being made in our understanding of somatic mutations that allow and accompany cancer development. In this review we discuss whether it is currently possible to use these new discoveries to aid the reduction of cancer mortality by reducing risk of disease, improving prognosis, and keeping complications due to treatment to a minimum. Findings from GWAS have mostly been used to predict risk, but there is the potential to use them for prognostication and even treatment prediction. Expression arrays have identified prognostic patterns for breast cancer, but few reliable patterns are available for treatment prediction. More importantly, virtually no genetic signatures are available to predict morbidity from treatment. Thus, there is a need to bring different biological techniques together and integrate them with existing clinical oncological care for a simultaneous risk and outcome assessment. PMID- 20359665 TI - Initial human experience with restrictive duodenal-jejunal bypass liner for treatment of morbid obesity. AB - BACKGROUND: The duodenal-jejunal bypass liner is an endoscopically placed and removable intestinal liner that creates a duodenal-jejunal bypass, leading to diabetes improvement and weight loss. The aim of the present study was to evaluate the clinical effects and safety of the duodenal-jejunal bypass liner combined with a restrictor orifice (flow restrictor). METHODS: The device was endoscopically implanted in 10 patients (body mass index 40.8 +/- 4.0 kg/m(2)) and removed after 12 weeks. Dilation of the restrictor orifice was performed as clinically indicated with a 6-, 8-, or 10-mm diameter through-the-scope balloon. The measured outcomes included the percentage of excess weight loss, total weight loss, adverse events, and gastric emptying (GE) at baseline, weeks 4 and 12 of implantation, and 3-5 months after device removal. GE was measured by scintigraphy at 1, 2, and 4 hours after implantation. RESULTS: The percentage of excess weight loss and total weight loss at explantation was 40% +/- 3% (range 21 64%) and 16.7 +/- 1.4 kg (range 12.0-26.0), respectively. The 4-hour GE was 98% +/- 1% at baseline, 72% +/- 6% at 4 weeks (P = 0.001 versus baseline), and 84% +/ 5% at 12 weeks (P <.05 versus baseline). After explantation, the rate of GE returned to normal in 7 of 8 subjects, but remained slightly delayed in 1 subject (84% at 4 hours). Episodes of nausea, vomiting, and abdominal pain required endoscopic dilation of the restrictor orifice with a 6-mm through-the-scope balloon in 7 patients and a 10-mm balloon in 1, with no clinically significant adverse events. CONCLUSION: Endoscopic implantation of a combination flow restrictor and duodenal-jejunal bypass liner induced substantial weight loss. The implanted patients exhibited delayed GE that was reversed after device removal. PMID- 20359666 TI - Comment on: Initial human experience with restrictive duodenal-jejunal bypass liner for treatment of morbid obesity. PMID- 20359667 TI - Favorable internal hernia rate achieved using retrocolic, retrogastric alimentary limb in laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: The present study was performed at a tertiary care university hospital. The present study examined the incidence of internal hernia (IH) in our series of laparoscopic Roux-en-Y gastric bypass (LRYGB) with retrocolic, retrogastric routing of the alimentary limb accompanied by routine secure closure of all mesenteric defects. METHODS: During a 4-year period, 847 patients underwent LRYGB. Our operative technique included retrocolic, retrogastric placement of the alimentary limb. The enteroenterostomy mesenteric defect, mesocolic defect, and Petersen defect were routinely closed in running fashion with nonabsorbable suture. RESULTS: The study population had a mean age of 42.4 +/- 9.3 years and a mean preoperative body mass index of 45.3 +/- 5.6 kg/m(2). The mean operative time was 154 +/- 25 minutes. The mean excess body weight loss at 1 year was 70%. The incidence of IH among this large study population was 0%. A total of 11 patients (1.3%) presented with symptoms concerning for IH, most commonly nausea, vomiting, and crampy abdominal pain, from 1 month to 6 years after the initial surgery. On re-exploration, 4 patients had adhesive small bowel obstruction, 4 had adhesions without obstruction, 1 had small bowel intussusception, and 2 patients had negative findings. CONCLUSION: IH is a serious complication of LRYGB that can lead to catastrophic morbidity and mortality. We advocate vigilant screening for this complication and laparoscopic exploration for patients with worrisome symptoms. Our data have indicated that a routine and consistent technique to securely close the mesenteric defects can significantly reduce the risk of IH associated with retrocolic, retrogastric placement of the alimentary limb during LRYGB. PMID- 20359668 TI - Comment on: Favorable internal hernia rate achieved using retrocolic, retrogastric alimentary limb in laparoscopic Roux-en-Y gastric bypass. PMID- 20359669 TI - Intensive care unit stay not required for patients with obstructive sleep apnea after laparoscopic Roux-en-Y gastric bypass. AB - BACKGROUND: Many programs admit morbidly obese patients with obstructive sleep apnea (OSA) to the intensive care unit after laparoscopic gastric bypass (LGB), fearing pulmonary complications. Our practice has been to admit these patients to the surgical floor. Our objective was to compare the perioperative course and outcomes in morbidly obese patients with OSA to those of patients without OSA undergoing LGB in a physician-led health system with a 325-bed community teaching hospital serving 19 counties. METHODS: We retrospectively reviewed the medical records of 650 patients who had undergone LGB from 2001 to 2008 and divided them into 2 groups: patients with OSA as confirmed by polysomnography (OSA group) and those without OSA (non-OSA group). The patients who reported a diagnosis of OSA without documentation confirming the diagnosis were excluded. The statistical analysis included t tests and chi-square tests. RESULTS: A total of 217 patients met the inclusion criteria for the OSA cohort and 368 for the non-OSA cohort. Of the 650 patients, 65 reported a history of OSA without confirmation and were excluded from the present study, leaving 585 patients. The demographic data were similar between the 2 groups, and no difference was found between the OSA and non OSA groups for the length of postanesthesia care unit stay (105.4 versus 106.3 minutes), length of hospital stay (2.2 days for both groups), and 30-day major complication rate (3.7% versus 5.2%). No deaths and no intensive care unit admissions for pulmonary complications occurred in either group. CONCLUSION: The results of our study have shown that morbidly obese patients with OSA undergoing LGB have a perioperative course and postoperative pulmonary complication rate similar to that of patients without OSA. Thus, routine admission to the intensive care unit after LGB in patients with OSA is not indicated. PMID- 20359670 TI - Gastric bypass and On-Q pump: effectiveness of Soaker Catheter system on recovery of bariatric surgery patients. AB - BACKGROUND: The continuous infusion of ropivacaine is effective in controlling pain for a wide variety of surgical procedures and reducing opioid adverse effects and dependency. The present study assessed the efficacy of ropivacaine infusion using the I-Flow dual Soaker Catheter system at the surgical site for bariatric surgery recovery at the Dallas Veterans Affairs Medical Center Hospital (Dallas, TX). We hypothesized that patients receiving ropivacaine would report lower levels of morphine requirement and pain, would have shorter hospital stays, and would return to ambulating faster than patients in the control group. METHODS: A total of 45 patients undergoing Roux-en-Y gastric bypass surgery were randomized to 1 of 2 treatment groups, with a target study population of 50 patients, receiving either .2% ropivacaine (n = 24) or saline solution (n = 21). Before incision closure, the surgeon infiltrated the surrounding tissues with 30 mL of ropivacaine (.5%) or saline solution. The catheter was then placed in both the subfascial space and subcutaneously. Next, the infusion pump was connected to the Soaker Catheters to complete the system design and deliver solution to the surgical site. RESULTS: No significant differences were found in the pain scores, morphine requirement, or length of stay between the 2 groups. The ropivacaine group interval to sitting up was one half day shorter than that of patients receiving saline (P = .038). CONCLUSIONS: Patients receiving ropivacaine were found to ambulate much more quickly than did the control group patients. This could be very beneficial in reducing the complications from blood clots and improving patient recovery and overall well-being after surgery by assisting with a quicker return to activities of daily living and reducing the dependence on the nursing staff. PMID- 20359671 TI - Duodenal obstruction due to erosion and migration of an adjustable gastric band: a novel endoscopic approach to management. PMID- 20359672 TI - Revisional bariatric surgery can be done safely: it's nice to confirm our personal clinical experience with data. PMID- 20359673 TI - Self-directed physiatric education program in physical medicine and rehabilitation: foreword: pediatric rehabilitation. PMID- 20359674 TI - Pediatric rehabilitation: 2. Environmental factors affecting participation. AB - OBJECTIVE: This self-directed learning module highlights the environmental factors that influence the participation of children and youth with disabilities in life situations, including activities of self-care, mobility, socialization, education, recreation, and community life. It is part of the study guide on pediatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and pediatric medicine. This module emphasizes the participation of children with disabilities in adapted sports and reviews mobility devices to promote function, in the context of the International Classification of Functioning and in reference to the Americans with Disabilities Act. It provides the physiatrist with strategies to promote community participation, functional independence and healthcare transitions for children with disabilities as they approach adulthood. The goal of this article is to improve the learner's treatment strategies to maximize the participation of children and youth with disabilities in all settings, particularly schools and communities. PMID- 20359675 TI - Pediatric rehabilitation: 3. Facilitating family-centered treatment decisions. AB - OBJECTIVE: This self-directed learning module focuses on the role of accurate diagnosis, psychological support, and family integration of children who have chronic impairments such as pain, spasticity, or cognitive disability. It is part of the study guide on pediatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and pediatric medicine. The role of therapeutic, medical (traditional and nontraditional) and psychological interventions that improve family and individual function are emphasized. The goal of this article is to refine a learner's knowledge of the impact family-centered care can have on the medical, psychological, financial, and functional capabilities of families to improve treatment decisions in the context of children with disability. PMID- 20359676 TI - Pediatric rehabilitation: 4. Prescribing assistive technology to promote community integration. AB - OBJECTIVE: This self-directed learning module highlights the equipment and assistive technology needs of children and youth with disabilities. This article specifically focuses on preparing families and patients for equipment transitions that occur over the course of childhood and adolescence including progressing from stroller to wheelchair to powerchair, as well as job training and use of augmentative communication. It is part of the study guide on pediatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and pediatric medicine. The goal of this article is to modify the learner's current practice techniques to ensure that assistive technology is used to promote community integration from early childhood through transition and into adulthood. PMID- 20359677 TI - Pediatric rehabilitation: 1. Common medical conditions in children with disabilities. AB - OBJECTIVE: This self-directed learning module focuses on the physiatric management of the common morbidities associated with pediatric traumatic brain injury and cerebral palsy. It is part of the study guide on pediatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and pediatric medicine. The goal of this article is to enhance the learner's knowledge regarding current physiatric management of complications related with pediatric traumatic brain injury and cerebral palsy. PMID- 20359678 TI - Pediatric rehabilitation: 5. Transitioning teens with disabilities into adulthood. AB - OBJECTIVE: This self-directed learning module focuses on preparing adolescent patients with special health care needs for adulthood by promoting their independence in their own self-care; helping them to navigate issues of sexuality, marriage, and parenting; preparing the patient and family to make guardianship decisions during the transition between childhood and adulthood; and planning for higher education or vocation. Emphasis will be on the role of the physiatrist in providing this guidance and its importance in improving the patient's quality of life. It is part of the study guide on pediatric rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation and pediatric medicine. The goal of this article is to refine the learner's knowledge of preparing adolescent patients with special health care needs for adulthood to improve their quality of life. PMID- 20359679 TI - Sports and disability. AB - Participation in recreational and competitive sports at an early age has long been touted as a positive influence on growth and development, and for fostering lifelong healthy lifestyles. The benefits of an active lifestyle include not only fitness, but the promotion of a sense of inclusion and improved self-esteem. These benefits are well documented in all populations, and their importance has been summarized in the recent Healthy People 2010 guidelines. The American Academy of Pediatrics has recently produced a summary statement on the benefits of activity for disabled children. They note that children with disabilities tend to have an overall lower level of fitness and an increased level of obesity. For this population, developing a lifelong desire to be active can be a simple means for limiting illness and much of the morbidity associated with sedentary lifestyles often associated with disability. For disabled youth, participation in disabled sports programs available nationally and internationally can be an effective means to promote such precepts. The goal of this focused review is to improve the learner's knowledge of the positive impact that active lifestyles can have on overall health in the disabled youth population and, as a result, modify their practice by incorporating recreational and competitive sport activities as part of improving overall patient care. PMID- 20359680 TI - Physiatrists as pain medicine physicians. PMID- 20359681 TI - The diagnostic validity of hip provocation maneuvers to detect intra-articular hip pathology. AB - OBJECTIVE: To determine which hip provocation maneuvers best predict the presence of an intra-articular hip pathology. DESIGN: Prospective diagnostic study. SETTING: Musculoskeletal clinic at a university-based multispecialty group practice. PARTICIPANTS: Fifty subjects referred for intra-articular hip injection under fluoroscopic guidance. INTERVENTIONS: Subjects were examined with 4 pain provocation maneuvers before and after anesthetic intra-articular hip injection administered under fluoroscopic guidance. MAIN OUTCOME MEASUREMENTS: Presence of intra-articular hip pain generator was confirmed by > or =80% improvement on visual analog scale after intra-articular hip injection. RESULTS: The most sensitive tests were flexion abduction external rotation (FABER) test and internal rotation over pressure (IROP) maneuver. For the FABER test, sensitivity was 0.82 (95% CI 0.57-0.96); sensitivity for the IROP maneuver was 0.91 (95% CI 0.68-0.99). The most specific test was the Stinchfield maneuver, with specificity at 0.32 (95% CI 0.14-0.55). FABER and IROP had the highest positive predictive value, with 0.46 (95% CI 0.28-0.65) and 0.47 (95% CI 0.29-0.64), respectively. IROP had the highest negative predictive value at 0.71 (95% CI 0.25-0.98). CONCLUSIONS: IROP and FABER may be worthwhile components of the clinical evaluation of hip pain to determine intra-articular hip pathology. These tests are nonspecific and therefore not necessarily negative in the absence of intra articular hip pathology. These hip provocation maneuvers are a useful part of an evaluation that includes history, further examination findings, and other diagnostic studies. PMID- 20359682 TI - Understanding and critically appraising evidence about diagnostic tests. PMID- 20359683 TI - Changes in transversus abdominis thickness with use of the abdominal drawing-in maneuver during a functional task. AB - OBJECTIVE: The purpose of this study was to examine an individual's ability to produce an increase in transversus abdominis (TrA) thickness during the performance of a functional task with the use of the abdominal drawing-in maneuver (ADIM). DESIGN: Within-subject repeated measures analysis of variance was used to examine the effects of the ADIM and a loaded forward-reaching activity on the dependent variable of TrA thickness. SETTING: Laboratory. PARTICIPANTS: Convenience sample of 8 women and 8 men, asymptomatic, with a mean age of 27.6 +/- 7.1 years. INTERVENTIONS: Ultrasound imaging measurements were recorded during 4 conditions: (1) while the patient was standing without the ADIM; (2) while the patient was standing with the ADIM; (3) during a loaded forward-reaching activity without the ADIM; and (4) during a loaded forward reaching activity with the ADIM. MAIN OUTCOME MEASURES: Thickness of the TrA muscle. RESULTS: The measurement obtained by an investigator blinded to the condition revealed statistically significant differences in the thickness of the TrA between all uncontracted conditions as compared with all contracted conditions. No statistically significant difference in the thickness of the TrA in the contracted states during quiet standing versus loaded forward reach was observed. CONCLUSION: Subjects in this study demonstrated the ability to voluntarily activate the TrA during upright static and functional tasks. Additionally, the TrA thickness may change in a direction-specific manner. These findings support a protective role of the ADIM during functional activity and may add information to ways for promoting low back pain prevention. Future studies should include the effectiveness in the use of ADIM during functional tasks for the prevention of low back pain. PMID- 20359684 TI - Postinjury personality and outcome in acquired brain injury: the Millon Behavioral Medicine Diagnostic. AB - OBJECTIVE: To examine the relationship between postinjury personality and outcome in individuals with acquired brain injury. It was hypothesized that patients with differing levels of Introversive, Dejected, and Oppositional coping styles as described by Millon's Theory of Personality would show different outcomes after completion of a rehabilitation program. DESIGN: A retrospective chart review and completion of an outcome assessment was undertaken to examine study hypotheses. SETTING: A postacute brain injury rehabilitation program. PARTICIPANTS: Fifty patients who completed the rehabilitation program between 2005 and 2008, who were 18 years of age or older, who possessed at least a sixth-grade reading level, and who completed a valid Millon Behavioral Medicine Diagnostic (MBMD) were selected. Rehabilitation therapists who worked with these patients were also recruited to assess patient outcomes. METHODS: Charts of patients that met inclusion criteria were reviewed. Rehabilitation therapists completed the outcome measure retrospectively. The MBMD was used to predict outcome. The MBMD is a self-report questionnaire designed to assess psychosocial factors that relate to the course of medical treatment in chronic illness. MAIN OUTCOME MEASUREMENTS: The Mayo Portland Adaptability Inventory (MPAI-4) was used to assess patient outcome. It is a 29-item assessment designed to evaluate the common physical, cognitive, emotional, behavioral, and social issues after acquired brain injury. RESULTS: Findings supported our hypotheses that patients with differing levels of Introversive and Oppositional Coping Styles would have significantly different outcomes after rehabilitation. Thus, individuals with mild/moderate to moderate/severe limitations had significantly greater scores on the Introversive and Oppositional coping compared with individuals with more successful outcomes. CONCLUSIONS: The results of this study support the idea that postinjury personality is an important factor in understanding outcome after completion of a brain-injury rehabilitation program. Personality variables accounted for significant variance above and beyond variance accounted for by the severity of the injury alone. These findings have important implications for the development and implementation of rehabilitation treatment planning. PMID- 20359685 TI - A descriptive study on vitamin D levels in individuals with spinal cord injury in an acute inpatient rehabilitation setting. AB - OBJECTIVE: To determine the prevalence of inadequate or severely deficient levels of vitamin D in patients with spinal cord injury (SCI) admitted to an inpatient rehabilitation service and to describe any associations between patient demographics and injury characteristics and vitamin D levels. DESIGN: Retrospective case series. SETTING: Academic inpatient SCI rehabilitation program. SUBJECTS: One hundred patients with SCI who were consecutively admitted to acute inpatient rehabilitation from January to December 2007. METHODS: Data were retrospectively abstracted from the patient's medical chart. OUTCOME MEASURE: VitD-25(OH). RESULTS: The prevalence of VitD-25(OH) inadequacy or severe deficiency was 93% in this sample of patients with SCI. The mean VitD-25(OH) level was 16.29 +/- 7.73 ng/mL, with a range from 7.00 to 36.80 ng/mL. Twenty-one percent of the sample had VitD-25(OH) levels that were considered as severely deficient (< or =10 ng/mL). African-American subjects had statistically significant lower mean VitD-25(OH) levels compared with Caucasian subjects (12.96 versus 17.79 ng/mL; P = .003). Persons with an incomplete injury had significant lower mean VitD-25(OH) levels compared with complete injuries (14.64 versus 18.15 ng/mL; P = .023). CONCLUSIONS: Inadequate or severely deficient levels of VitD 25(OH) were highly prevalent in patients with SCI admitted to an acute inpatient rehabilitation service. Evaluation of serum VitD-25(OH) levels are recommended in patients with SCI because low levels may contribute to osteoporosis. PMID- 20359686 TI - Making sense of intention-to-treat. PMID- 20359687 TI - Manually-assisted versus robotic-assisted body weight-supported treadmill training in spinal cord injury: what is the role of each? PMID- 20359688 TI - Re: diabetic lumbosacral radiculoplexus neuropathy. PMID- 20359689 TI - Re: post-polio syndrome. PMID- 20359690 TI - ACh- and VIP-induced vasorelaxation in rabbit facial artery after carotid artery occlusion. AB - OBJECTIVES: The influence of carotid artery occlusion (10, 30 and 60 min) on regulatory mechanisms implicated in the vasorelaxant responses of isolated glandular branch of rabbit facial artery to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) was examined. DESIGN: In organ bath studies with arterial rings precontracted with phenylephrine (1 microM), before and after carotid artery occlusion, changes in isometric tension were recorded. RESULTS: Endothelium-dependent vasorelaxation by ACh and endothelium-independent vasorelaxation by VIP were significantly reduced, started from 30 and 10 min of carotid occlusion, respectively. Inhibitory effect of indomethacin on ACh vasorelaxation was enhanced whilst effect of N(G)-nitro-L-arginine reduced, started from 30 min of carotid occlusion. Sodium nitroprusside-induced vasorelaxation was not changed after carotid occlusion. Inhibition of VIP vasorelaxation by L-N(omega)-nitroarginine-2,4-L-diaminobutyric-amide, was reduced, started from 30 min of carotid occlusion. Forskolin enhanced VIP-induced vasorelaxation in control rings but this effect was reduced started from 30 min of occlusion. In the presence of VIP, vasorelaxant effect of ACh was increased; the increase was reduced, started from 10 min of carotid occlusion. CONCLUSIONS: The present investigation provides evidence for the decreased responsiveness to both, ACh-endothelium-dependent and VIP-endothelium-independent vasorelaxation in rabbit facial artery after carotid occlusion. In addition, the data suggest that ischaemia alters contribution of endothelial nitric oxide (eNO) and prostaglandin to ACh, and vascular smooth muscle's cAMP and neuronal NO to VIP vasorelaxant effects. PMID- 20359691 TI - Is it mere distraction? Peri-traumatic verbal tasks can increase analogue flashbacks but reduce voluntary memory performance. AB - Several experiments have shown that we can reduce the frequency of analogue flashbacks with competing tasks presented during a trauma film (i.e. peri traumatically). A "distraction" hypothesis suggests that any competing task may reduce flashbacks due to distraction and/or a load on executive control. Alternatively, a "modality" hypothesis based on clinical models of PTSD suggests that certain tasks will not protect against intrusions (Experiment 1) and could actually increase them (Experiment 2). Experiment 1 contrasted two concurrent tasks, Verbal Interference (counting backwards in threes) and Visuospatial tapping, against a no-task Control condition during trauma film viewing. The Visuospatial group had significantly fewer intrusions of the film over 1-week than the Control group. Contrary to a distraction account, the Verbal Interference group did not show this effect. Using a larger sample, Experiment 2 showed that the Verbal Interference group (counting backwards in sevens) had more intrusions (and inferior voluntary memory) than no-task Controls. We propose that this is in line with a modality hypothesis concerning trauma flashbacks. Disrupting verbal/conceptual processing during trauma could be harmful for later flashbacks. PMID- 20359692 TI - Behavioural group therapy for obsessive-compulsive disorder in Norway. An open community-based trial. AB - The aim of the current study was to test the effectiveness of ERP-based 12 weeks group therapy for OCD patients in a community-based, general Norwegian outpatient clinic. The sample consisted of 54 patients diagnosed with OCD. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Beck Depression Inventory (BDI) and the Spielberger State Anxiety Inventory (STAI-S) were administered before treatment, after treatment and at 3- and 12-month follow-ups. Analyses with mixed models for repeated measurements showed that group behavioural therapy offered to OCD patients significantly improved ratings of obsessive-compulsive symptoms, depression and anxiety. These improvements were maintained at 3- and 12-month follow-ups and an additional reduction in obsessive-compulsive symptoms was observed from post-treatment to 3-month follow-up. However, the delayed effect of therapy was no longer present at 12-month follow-up. The results also revealed that the patients had a lower chance for an increased outcome category (e.g. from unchanged to improved or recovered) with high scores on STAI-S at the given observation times (post-treatment, 3- and 12-months follow-ups). Depressive symptoms (BDI) at post-treatment and follow-ups had no significant influences on the three categories of outcome for OCD. In conclusion, the results indicate that behavioural group therapy can successfully be delivered to patients with considerable comorbidity in a real world setting conducted by therapists with limited training in the CBT. PMID- 20359693 TI - When should clinicians switch treatments? An application of signal detection theory to two treatments for women with alcohol use disorders. AB - Statistical application of signal detection theory has been used to study the clinical utility of early treatment response in a range of treatments and psychiatric disorders. The current study sought to examine the predictive value of weekly within-treatment drinking using receiver operator curves (ROCs) and zero-inflated Poisson (ZIP) regression in 102 women with alcohol use disorders (AUDs) randomized to either alcohol behavioral individual treatment (ABIT; n = 52) or alcohol behavioral couples treatment (ABCT; n = 50). ROC analyses indicated that failure to achieve or sustain abstinence by the end-of-treatment and one-year follow-up was predicted with reasonable accuracy by week 4 percent days abstinent (PDA) in ABIT. ZIP models yielded similar results with evidence for within-treatment PDA with week 6 PDA predicting both the abstinence as well as percent days drinking at the end-of-treatment and one-year follow-up. Within treatment PDA was a significantly better predictor of outcomes for ABIT than ABCT, despite a better overall treatment response for ABCT. Implications for stepped care models of alcohol treatment are discussed and recommendations for future research made. PMID- 20359695 TI - Compensation and disease severity on the memory-related activations in mild cognitive impairment. AB - BACKGROUND: Alzheimer's disease is a neurodegenerative disease with progressive cognitive impairments that are likely to affect the compensatory mechanisms and the cerebral activation patterns of the patients. METHODS: Functional neuroimaging was used to test the effect of disease severity on the brain activation of persons at risk for Alzheimer's disease and to highlight the process of compensation in some of these individuals. This was done for the verbal learning of either semantically related or semantically unrelated word pairs. Twenty-six persons with mild cognitive impairment (MCI) were separated into two groups, MCI higher-cognition and MCI lower-cognition, with a split median on their scores for the Mattis Dementia Rating Scale. A group of 14 healthy older adults were matched to the MCI participants. RESULTS: In both task conditions, MCI higher-cognition activated additional regions, relative to control subjects, in the right ventrolateral and dorsolateral prefrontal brain areas. Additional areas of hyperactivation were found in the right prefrontal area 45 when encoding semantically related word pairs and in the left hippocampus during encoding of unrelated word pairs. In contrast, MCI lower-cognition failed to show additional prefrontal activations when compared with healthy control subjects and showed decreased activation in posterior areas. CONCLUSIONS: These results are in line with compensation occurring at the beginning of the MCI continuum and with the breakdown of compensation in patients experiencing more severe symptoms. PMID- 20359694 TI - Orphanin FQ/nociceptin not only blocks but also reverses behavioral adaptive changes induced by repeated cocaine in mice. AB - BACKGROUND: Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL1) receptor, blocks cocaine sensitization in rats. In this study, we tested whether OFQ/N would block sensitization to the motor stimulatory and conditioned rewarding actions of cocaine in mice. We also examined whether OFQ/N, given to cocaine-sensitized mice, would reverse the sensitized response and whether it would prevent the amplified sensitized response induced by a second cocaine-sensitizing regimen in sensitized mice. METHODS: ORL1 knockout and wild-type mice were treated with saline or OFQ/N before saline or cocaine on Days 1-3 and tested for sensitization on Day 8. Additionally, wild-type mice were treated similarly but tested for the conditioned rewarding action of cocaine, in which mice were tested for place preference before and after single conditioning with cocaine. Furthermore, mice were rendered sensitized, treated with saline or OFQ/N before saline or cocaine on Days 13-15, and received cocaine on Day 20 to test whether OFQ/N would reverse sensitization or block the amplified sensitized response induced by a second cocaine-sensitizing regimen in sensitized mice. RESULTS: OFQ/N blocked cocaine-induced psychomotor sensitization in wild-type but not knockout mice. It also blocked sensitization to the conditioned rewarding action of cocaine and reversed a preexisting locomotor sensitized response. Furthermore, OFQ/N prevented the amplified sensitized response that developed following a second cocaine sensitizing regimen given to sensitized mice. CONCLUSIONS: These results illustrate that OFQ/N not only blocks but also reverses maladaptive behavioral changes induced by repeated cocaine treatment in mice. PMID- 20359696 TI - Rapid cerebral amyloid binding by Abeta antibodies infused into beta-amyloid precursor protein transgenic mice. AB - BACKGROUND: Passive immunization for the treatment of Alzheimer's disease (AD) was rapidly translated into clinical trials. However, basic mechanisms of AD immunotherapy remain only partially understood. METHODS: We analyzed the dynamic changes of amyloid-beta (Abeta) levels in plasma, brain, and cerebrospinal fluid (CSF) as well as cerebral amyloid binding by Abeta antibody after a single beta1 antibody infusion into APP(Swedish) and APP(wildtype) transgenic mice at preplaque and plaque-bearing age. RESULTS: Following intravenous Abeta antibody treatment, plasma Abeta increased rapidly, reaching significantly higher levels in preplaque compared with plaque-bearing mice, whereas cerebral and CSF Abeta remained unchanged. Strikingly, Abeta antibodies exhibited strong cerebral amyloid plaque binding rapidly after intravenous administration in a subset of animals with more severe vascular amyloid. CONCLUSIONS: Rapid plasma Abeta increase after Abeta antibody infusion results primarily from stabilization of Abeta. Nevertheless, the smaller plasma Abeta increase in plaque-bearing mice might be of diagnostic use. Importantly, intravenously administered antibodies can rapidly bind to cerebral plaques, potentially facilitated by vascular-amyloid mediated damage of the blood-brain barrier. PMID- 20359697 TI - Impaired decision making in oppositional defiant disorder related to altered psychophysiological responses to reinforcement. AB - BACKGROUND: When making decisions, children with oppositional defiant disorder (ODD) are thought to focus on reward and ignore penalty. This is suggested to be associated with a state of low psychophysiological arousal. METHODS: This study investigates decision making in 18 children with oppositional defiant disorder and 24 typically developing control subjects. Children were required to choose between three alternatives that carried either frequent small rewards and occasional small penalties (advantageous), frequent large rewards and increasing penalties (seductive), or frequent small rewards and increasing penalties (disadvantageous). Penalties in the seductive and disadvantageous alternatives increased either in frequency or magnitude in two conditions. Heart rate (HR) and skin conductance responses to reinforcement were obtained. RESULTS: In the magnitude condition, children with ODD showed an increased preference for the seductive alternative (carrying large rewards); this was not observed in the frequency condition. Children with ODD, compared with typically developing children, displayed greater HR reactivity to reward (more HR deceleration) and smaller HR reactivity to penalty. Correlation analyses showed that decreased HR responses to penalty were related to an increased preference for large rewards. No group differences were observed in skin conductance responses to reward or penalty. CONCLUSIONS: The findings suggest that an increased preference for large rewards in children with ODD is related to a reduced cardiac reactivity to aversive stimuli. This confirms notions of impaired decision making and altered reinforcement sensitivity in children with ODD and adds to the literature linking altered autonomic control to antisocial behavior. PMID- 20359698 TI - Seeing gray when feeling blue? Depression can be measured in the eye of the diseased. AB - BACKGROUND: Everyday language relates depressed mood to visual phenomena. Previous studies point to a reduced sensitivity of subjective contrast perception in depressed patients. One way to assess visual contrast perception in an objective way at the level of the retina is to measure the pattern electroretinogram (PERG). To find an objective correlate of reduced contrast perception, we measured the PERG in healthy control subjects and unmedicated and medicated patients with depression. METHODS: Forty patients with a diagnosis of major depression (20 with and 20 without medication) and 40 matched healthy subjects were studied. Visual PERGs were recorded from both eyes. RESULTS: Unmedicated and medicated depressed patients displayed dramatically lower retinal contrast gain. We found a strong and significant correlation between contrast gain and severity of depression. This marker distinguishes most patients on a single-case basis from control subjects. A receiver operating characteristic analysis revealed a specificity of 92.5% and a sensitivity of 77.5% for classifying the participants correctly. CONCLUSIONS: Because PERG recording does not depend on subjective ratings, this marker may be an objective correlate of depression in human beings. If replicated, PERG may be helpful in further animal and human research in depression. PMID- 20359700 TI - Kinetic and thermodynamic properties of MAG antagonists. AB - Paraplegia is caused by injuries of the central nervous system (CNS) and especially young people suffer from these severe consequences as, for example, the loss of motor functions. The lack of repair of the injured nerve strands originates from the inhibitory environment for axon regeneration in the CNS. Specific inhibitory proteins block the regrowth of nerve roots. One of these neurite outgrowth inhibitors is the myelin-associated glycoprotein (MAG), which is a member of the Siglec family (sialic acid-binding immunoglobulin-like lectin). In previous studies, we identified potent small molecule MAG antagonists. In this communication, we report new neuraminic acid derivatives modified in the 4- and 5-position, and the influence of various structural modifications on their kinetic and thermodynamic binding properties. PMID- 20359699 TI - Oxytocin and the development of parenting in humans. AB - BACKGROUND: The nonapeptide oxytocin (OT) has been repeatedly implicated in processes of parent-infant bonding in animal models; yet, its role in the development of human parenting has received less attention and no research has addressed the involvement of OT in the transition to fatherhood. METHODS: Using a prospective longitudinal design, 160 cohabitating mothers and fathers and their firstborn infant were visited at home during the first postpartum weeks and again at 6 months postpartum. Mothers' and fathers' plasma OT was analyzed at each time point with enzyme-linked immunosorbent assay methodology. Interactions between each parent and the infant were observed in the postpartum and microcoded for parenting behavior. RESULTS: Overall, parental OT increased across the study period and there were no differences between maternal and paternal OT at each time point. Oxytocin showed high intraindividual stability across the first 6 months of parenting and the OT levels of husband and wife were interrelated at both assessments. Maternal OT was related to the amount of affectionate parenting behaviors, including "motherese" vocalizations, the expression of positive affect, and affectionate touch, whereas paternal OT correlated with the degree of stimulatory parenting behaviors, including proprioceptive contact, tactile stimulation, and object presentation. CONCLUSIONS: Results are the first to describe plasma OT levels in new fathers and mothers across the transition to parenthood in relation to maternal and paternal typical parenting behaviors. These data may provide a normative basis for the study of parenting under conditions of high risk. PMID- 20359701 TI - Unusual amnesia in a patient with VGKC-Ab limbic encephalitis: a case study. AB - We describe the case of a patient with confirmed voltage-gated potassium channel antibody-associated encephalitis (VGKC-Ab). MRI studies revealed bilateral hyper intensity in the hippocampi, with their volumes preserved. At presentation, the patient's anterograde and retrograde memory skills were found to be impaired and he showed fluctuation in his ability to recall familiar information. Following treatment with immunotherapy, his condition improved considerably and, in a series of follow up assessments, he performed satisfactorily (i.e., within the average range or above) on formal tests of memory, as well as on a range of other cognitive tests, including tests of executive function. By contrast, in the context of contemporaneous unstructured interviews, he showed a strong tendency to confabulate. We argue that the reported case broadens the phenomenology of VGKC-Ab limbic encephalitis and raises important theoretical questions about the aetiology of this patient's most unusual memory disorder. PMID- 20359702 TI - [Utility of combined therapy in the prevention and treatment of the cardiovascular disease]. AB - Although blood pressure control is crucial in patients with hypertension, current clinical practice guidelines recommend that the goal of treatment should be aimed at not only reducing blood pressure values but decreasing global cardiovascular risk. Available data suggest that blood pressure and LDL-cholesterol control rates, two of the most common cardiovascular risk factors, are low, not only in the primary care setting but also in specialists setting. Clinical trials, such as the Anglo-Scandanavian Cardiac Outcomes Trial (ASCOT), have demonstrated that the integration of a multifactorial approach through the treatment of different risk factors effectively reduces the risk of cardiovascular morbidity and mortality. The aim of this review was to update the current knowledge about the combined therapy of different risk factors in the hypertensive population. PMID- 20359703 TI - [What does process management contribute to the analysis of the internal medicine activity in the hospitals of the national health system?]. PMID- 20359704 TI - [Compass for newly-graduated doctors]. AB - Taking advantage of the arrival to our hospital of a new group of medical residents, I believe this offers a good moment to reflect not on specific ways to resolve certain problems, but rather on the very nature of our profession. PMID- 20359705 TI - [The minor and his/her health care autonomy]. AB - The evolution of the human being from birth to death goes through successive stages that do not respond to standards that can be generalized. The evolution is a discovery that the child experiences and that is observed by those around the child. There are biological factors that mark the development. However, the decisive influence of the family setting, their financial and social status and the rest of the conditions of life under which the child is developing must not be overlooked. PMID- 20359707 TI - Do we follow triage protocols? PMID- 20359706 TI - What do patients want? Expectations and perceptions of IVF clinic information and support regarding frozen embryo disposition. AB - OBJECTIVE: To describe frozen embryo holders' expectations and perceptions of IVF clinic information, support, and storage fees and their relevance to embryo disposition decision making. DESIGN: Qualitative interview study. SETTING: Three northern California IVF practices. PATIENT(S): One hundred six families (110 women and 74 men) with an average of six frozen embryos in storage for 5 years. INTERVENTION(S): Three in-depth interviews over 1 year. MAIN OUTCOME MEASURE(S): Thematic analysis of interview transcripts. RESULT(S): Although embryo holders expected that IVF clinics were under obligation to assist in the disposition decision and would be their main source of information, these expectations did not become manifest until years after embryo cryopreservation. Patients expressed a variety of preferences for the timing, format, and content of information and support, ranging from detailed written information to counselor/advocates that could provide logistical guidance and/or psychologic support. Embryo holders perceived an insufficiently defined infrastructure to facilitate donation to other couples, whereas donating to medical research was seen as less complicated and more likely to be encouraged and supported by physicians and clinics. Although increasing storage fees motivated disposition decision making, they could be interpreted as coercive and/or not reflective of actual clinic costs. CONCLUSION(S): Frozen embryo-holding patients' expectations of information and support to assist them with disposition decision making and embryo donation suggests that IVF clinics may benefit from a review of their frozen embryo counseling, storage, and disposition policies and procedures. PMID- 20359708 TI - Quality of triage. PMID- 20359709 TI - Self-inflicted penetrating injuries at a Level I Trauma Center. AB - INTRODUCTION: Although gunshot and stab wounds are a common cause of self inflicted injury, very little is understood about this mechanism of injury. The aim of this study was to characterise the epidemiology and outcomes of patients who injured themselves with a gun or sharp object. METHODS: After IRB approval, the LAC+USC Trauma Registry was utilised to identify all patients who sustained a self-inflicted injury caused by firearm (GSW) or stabbing (SW) from 1997 to 2007. Demographic data, injury characteristics, surgical interventions, and outcomes were abstracted and analysed. RESULTS: During the 11-year study period, a total of 753 patients (1.6%) were admitted for a self-inflicted injury. Of these, 369 (49.0%) had a self-inflicted penetrating injury, with 72 (19.5%) having sustained a GSW and 297 (80.5%) having a SW. Overall, the mean age was 36.4+/-15.8 years, 83.5% were male, with a mean ISS of 7.4+/-11.0. The most commonly injured body region in GSW patients was the head (76.4%), followed by the chest (15.3%) and in SW patients the upper extremity (37.0%), followed by the abdomen (36.4%). When compared to SW, GSW were significantly more frequent in males (21.4% vs. 9.8%, p=0.04), and were most commonly to the head (21.4% vs. 8.2%, p=0.02). Patients sustaining a GSW were more likely to be older than 55 years (22.2% vs. 8.4%, p<0.001). Intoxication was noted at presentation in 38.3% of screened GSW patients and 39.9% of SW patients. SW patients required operative intervention more frequently (40.9% vs. 22.2%, p<0.01), with 12.8% of them requiring exploratory laparotomy. However, patients who shot themselves were much more likely to die (66.7%) than those presenting with SW (1.7%). For those presenting with a GSW to the head, the mortality rate was even higher, at 80%. Mortality did not differ between males and females in either group. CONCLUSION: Although a self inflicted SW is far more common than a self-inflicted GSW, patients sustaining a GSW are more severely injured, and have a nearly 110-fold increased risk of death. Though less lethal, stab wounds still consume significant amounts of healthcare resources and incur large in-hospital costs. The average hospital charge incurred for treating these self-inflicted injuries was five times the amount spent per annum on American citizens. Self-inflicted penetrating injuries represent a golden opportunity for secondary prevention through psychiatric intervention. These interventions may not only preserve life but also improve resource utilisation. PMID- 20359710 TI - Stress, coping and burn-out in nursing students. AB - AIM: To explore the relationship between sources of stress and psychological burn out and to consider the moderating and mediating role played sources of stress and different coping resources on burn-out. BACKGROUND: Most research exploring sources of stress and coping in nursing students construes stress as psychological distress. Little research has considered those sources of stress likely to enhance well-being and, by implication, learning. METHOD: A questionnaire was administered to 171 final year nursing students. Questions were asked which measured sources of stress when rated as likely to contribute to distress (a hassle) and rated as likely to help one achieve (an uplift). Support, control, self-efficacy and coping style were also measured, along with their potential moderating and mediating effect on burn-out. FINDINGS: The sources of stress likely to lead to distress were more often predictors of well-being than sources of stress likely to lead to positive, eustress states. However, placement experience was an important source of stress likely to lead to eustress. Self efficacy, dispositional control and support were other important predictors. Avoidance coping was the strongest predictor of burn-out and, even if used only occasionally, it can have an adverse effect on burn-out. Initiatives to promote support and self-efficacy are likely to have the more immediate benefits in enhancing student well-being. CONCLUSION: Nurse educators need to consider how course experiences contribute not just to potential distress but to eustress. How educators interact with their students and how they give feedback offers important opportunities to promote self-efficacy and provide valuable support. Peer support is a critical coping resource and can be bolstered through induction and through learning and teaching initiatives. PMID- 20359711 TI - Chronic hepatitis B infection and risk of atherosclerosis-related mortality: A 17 year follow-up study based on 22,472 residents in Taiwan. AB - BACKGROUND: Conflicting results have been reported on the association of chronic hepatitis B infection with risks of atherosclerotic diseases previously. The present study aimed to clarify the association between HBsAg seropositivity and atherosclerosis-related/cardiovascular mortality prospectively in Taiwan, one of the most endemic areas for hepatitis B infection in the world. METHODS AND RESULTS: After excluding subjects with HCV infection, we followed up a total of 22,472 subjects aged 30-65 years, consisting of 18,541 HBsAg seronegatives and 3931 seropositives, for 17 years for mortality. Cox proportional hazard models were used to estimate the hazard ratios of mortality after adjustment for traditional risk factors, glomerular filtration rates and the competing risk of liver mortality. In multivariate Cox regression analysis, taking into account liver mortality as a competing risk, the fully adjusted hazard ratios (95% CIs) of mortality from ischemic heart disease, cerebrovascular disease, atherosclerotic disease and all cardiovascular disease were 0.98 (0.82-1.17, P=0.28), 0.86 (0.79-1.05, P=0.25), 0.84 (0.72-1.06, P=0.27), and 0.96 (0.82-1.13, P=0.21) respectively for HBsAg seropositives compared with HBsAg seronegatives. CONCLUSION: HBsAg seropositivity was not associated with increased mortality risks of atherosclerosis-related/cardiovascular diseases during 17-year follow up. HBsAg seropositivity might not be a significant predictor for atherosclerosis related/cardiovascular deaths. PMID- 20359712 TI - Serial decline of kidney function as a novel biomarker for the progression of atherothrombotic disease. AB - OBJECTIVE: Impaired kidney function is associated with cardiovascular disease. However, from the available data it cannot be discerned which of the two entities presents first and entails the other. If renal dysfunction is first, a dynamic decline in the estimated glomerular filtration rate (eGFR) should predict vascular events and prove a useful biomarker for atherothrombotic disease. We therefore tested the hypothesis that a decrease in kidney function predicts future vascular events in a high-risk population of angiographically characterized coronary patients. METHODS: We calculated the eGFR by the Mayo clinic quadratic equation at baseline and after two years in a high-risk population of 400 consecutive men undergoing coronary angiography, of whom 355 had coronary artery disease (CAD). Vascular events were recorded over six years. RESULTS: A serial decrease in kidney function from baseline to the follow-up visit two years later significantly predicted vascular events in the subsequent four years independently from the baseline eGFR with a standardized adjusted hazard ratio (HR) of 1.41 (1.13-1.76); p=0.003. This result proved robust after adjustment for age, BMI, hypertension, diabetes, LDL-C, HDL-C, smoking, and high sensitivity C-reactive protein (HR=1.41 [1.12-1.78]; p=0.004). The predictive power of eGFR loss was confirmed even after further adjustment for the presence of CAD at baseline (HR=1.43 [1.12-1.81]; p=0.004). In this fully adjusted model a 10 ml/min/1.73 m2 decrease in eGFR independently conferred a 31% increase in cardiovascular event risk (p=0.004). CONCLUSION: A decline of eGFR over two years strongly, significantly, and independently predicts vascular events over the subsequent four years. Declining eGFR is a readily obtainable and inexpensive candidate new biomarker for the progression of atherothrombotic disease. PMID- 20359713 TI - Synthesis and surface modification of mesoporous mcm-41 silica materials. AB - Surface modification offers a great opportunity to adjust both the pore diameter and surface properties of MCM-41 type organic-inorganic hybrid materials which result in materials of improved hydrothermal and mechanical stability. Therefore, MCM-41 silica, surface modified with organic ligands, are promising systems with engineered properties and attractive for advanced applications. In the present study, after optimization of the reaction conditions highly ordered MCM-41 silica spheres with uniform mesopores were prepared by the pseudomorphic transformation route. The effect of functionality and alkyl chain length of the alkyl ligands during surface modification was probed by using butyl and octylsilanes with two different functionalities. Due to steric hindrance, the longer chains are assumed to bind only on the outer silica surface and near the entrance of the pores, while the shorter chains are also able to bind to the interior mesopore walls. The resulting materials were comprehensively characterized before and after surface modification using nitrogen sorption techniques, XRD, SEM, solid-state NMR spectroscopy and FTIR spectroscopy. From chromatographic test measurements it was found that the separation power primarily depends on surface coverage and alkyl chain length. On the basis of the present data, surface modified mesoporous silica of MCM-41 type are very promising candidates for future chromatographic applications. PMID- 20359714 TI - Perceptions of parents, nurses, and physicians on neonatal intensive care practices. AB - OBJECTIVE: To identify satisfaction with neonatal intensive care as viewed by parents and healthcare professionals and to explore similarities and differences between parents and healthcare professionals. STUDY DESIGN: A 3-round Delphi method to identify neonatal care issues (round 1) and to determine the importance of these issues (rounds 2 and 3) was conducted among nurses (n = 84) and physicians (n = 14), followed by an exploratory survey among parents (n = 259). Main outcome measures were 92 neonatal care-related items. RESULTS: Sixty-eight nurses and 13 physicians completed all 3 rounds. The first round yielded 419 neonatal care related statements, which were clustered into 92 items. The survey was completed by 148 (57%) parents. Parents rated 25 of 92 care items significantly higher than did the professionals (effect size of Cohen's d, 0.31 to 1.14, P 4.5) are removed to a significant extent (approx. 85%), while hydrophilic compounds (log K(ow) < 3.5) are poorly removed (<20%). For biofiltration, the removal of chemicals appears to be compound-dependent, although this outcome involves several mechanisms, namely: i) physical filtration of total suspended solids, ii) volatilisation, iii) sorption, and iv) biotransformation of substances. Even if the complex processes within a biofilter system do not yield an accurate prediction of pollutant removal, two groups of chemicals can still be clearly identified: i) hydrophobic or volatile compounds, for which moderate to high removal rates are observed (from 50% to over 80%); and ii) hydrophilic, non-volatile and refractory compounds for which a low removal rate would be expected (<20%). PMID- 20359733 TI - A comparative study of complex formation in the reactions of gold(III) with Gly Gly, Gly-L-Ala and Gly-L-His dipeptides. AB - Proton NMR spectroscopy was applied to study the reactions of the dipeptides glycyl-glycine (Gly-Gly) and glycyl-L-alanine (Gly-L-Ala) with hydrogen tetrachloridoaurate(III) (H[AuCl(4)]). All reactions were performed at pH 2.0 and 3.0 and at 40 degrees C. The final products in these reactions were [Au(Gly-Gly kappa(3)N(G1),N(G2),O(G2))Cl] and [Au(Gly-L-Ala-kappa(3)N(G),N(A),O(A))Cl] complexes. Tridentate coordination of the corresponding dipeptides and square planar geometry of these Au(III) complexes was confirmed by NMR ((1)H and (13)C) spectroscopy. This study showed that at pH<3.0 the Au(III) ion was able to deprotonate the amide nitrogen atom. However this displacement reaction was very slow and the total concentration of the corresponding Au(III)-peptide complex formed after 5 days was less than 60% for the Gly-L-Ala or 70% for the Gly-Gly dipeptide. The kinetic data of the reactions between the Gly-Gly and Gly-L-Ala dipeptides and [AuCl(4)](-) were compared with those for the histidine-containing Gly-l-His dipeptide. The differences in the reactivity of these three dipeptides with the Au(III) ion are discussed. PMID- 20359734 TI - Synthesis and tubulin-binding properties of new allocolchicinoids. AB - Allocolchicinoids with B- and C-ring variations were synthesized using sequential enyne-metathesis/ Diels-Alder reactions (A-->AB-->ABC approach) and evaluated for their inhibitory effect on tubulin assembly in vitro. (-)-Allocolchicine 11 with methyl ester at C10 and (+/-)-cyclopropyl allocolchicinoid 32 exhibit similar activity than (-)-colchicine (1), probably derived from a similar flexibility in the biphenyl system. The presence of methyl ester at C10 led to a little loss in potency in comparison with the series with methyl ester at C9. A complete loss of activity was observed for allocolchicine 9 with methyl ester at C11. PMID- 20359735 TI - Chemical composition of fine particles in fresh smoke plumes from boreal wild land fires in Europe. AB - A series of smoke plumes was detected in Helsinki, Finland, during a one-month lasting period in August 2006. The smoke plumes originated from wildfires close to Finland, and they were short-term and had a high particulate matter (PM) concentration. Physical and chemical properties of fine particles in those smokes were characterised by a wide range of real-time measurements that enabled the examination of individual plume events. Concurrently PM(1) filter samples were collected and analysed off-line. Satellite observations employing MODIS sensor on board of NASA EOS Terra satellite with the dispersion model SILAM and the Fire Assimilation System were used for evaluation of the emission fluxes from wildfires. The model predicted well the timing of the plumes but the predicted PM concentrations differed from the observed. The measurements showed that the major growth in PM concentration was caused by submicrometer particles consisting mainly of particulate organic matter (POM). POM had not totally oxidised during the transport based on the low WSOC-to-OC ratio. The fresh plumes were compared to another major smoke episode that was observed in Helsinki during April-May 2006. The duration and the source areas of the two episode periods differed. The episode in April-May was a period of nearly constantly upraised level of long range transported PM and it was composed of aged particles when arriving in Helsinki. The two episodes had differences also in the chemical composition of PM. The mass concentrations of biomass burning tracers (levoglucosan, potassium, and oxalate) increased during both the episodes but different concentration levels of elemental carbon and potassium indicated that the episodes differed in the form of burning as well as in the burning material. In spring dry crop residue and hay from the previous season were burnt whereas in August smokes from smouldering and incomplete burning of fresh vegetation were detected. PMID- 20359737 TI - Semantic integration during metaphor comprehension in Asperger syndrome. AB - Previous research indicates severe disabilities in processing figurative language in people diagnosed on the autism spectrum disorders. However, this aspect of language comprehension in Asperger syndrome (AS) specifically has rarely been the subject of formal study. The present study aimed to examine the possibility that in addition to their pragmatic deficits, the difficulties in the comprehension of metaphors in AS may be explained by deficient linguistic information processing. Specifically, we aimed to examine whether a deficient semantic integration process underlies the difficulties in metaphor comprehension frequently experienced by persons with AS. The semantic integration process of sixteen AS participants and sixteen matched controls was examined using event related potentials (ERPs). N400 amplitude served as an index for degree of effort invested in the semantic integration process of two-word expressions denoting literal, conventional metaphoric, and novel metaphoric meaning, as well as unrelated word pairs. Large N400 amplitudes for both novel and conventional metaphors demonstrated the greater difficulties in metaphor comprehension in the AS participants as compared to controls. Findings suggest that differences in linguistic information processing cause difficulties in metaphor comprehension in AS. PMID- 20359736 TI - Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes. AB - OBJECTIVE: The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas. METHODS: Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro. RESULTS: Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P<0.05).Patients with cervical carcinomas positive for nuclear Notch3 expression had significantly shorter overall survival than their peers whose tumors did not express nuclear Notch3. Inactivation of Notch3 decreased cell proliferation and induced apoptosis in ME180 and SKGIIIb cell lines that overexpressed Notch3. Injection of a gamma-secretase inhibitor into ME180 cell tumors established on mice, demonstrated a reduction in tumor growth. CONCLUSION: Our findings suggest that Notch3 might play important role for the proliferation and survival of Notch3 overexpressing tumors and that inactivation of Notch3 may represent a new therapeutic avenue for cervical squamous cell carcinomas. PMID- 20359738 TI - Hydrofluoric acid on dentin should be avoided. AB - Hydrofluoric acid can be used for intra-oral repair of restorations. Contamination of tooth substrate with hydrofluoric acid cannot always be avoided. OBJECTIVES: To investigate the bonding effectiveness to hydrofluoric acid contaminated dentin by, micro-tensile bond strength testing, SEM and TEM. METHODS: For this study, 15 molar teeth were used of which dentin surfaces were subjected to five, different etching procedures. Group A, 37.5% phosphoric acid (Kerr Gel) (control group); group B, 37.5% phosphoric acid followed by 3% hydrofluoric acid (DenMat); group C, 37.5% phosphoric acid, followed by 9.6% hydrofluoric acid (Pulpdent); group D, 3% hydrofluoric acid followed by 37.5%, phosphoric acid; group E, 9.6% hydrofluoric acid followed by 37.5% phosphoric acid. After the bonding procedure (OptiBond FL, Kerr) a composite resin build-up (Clearfil AP-X, Kuraray), was made. After 1 week storage, specimens were prepared for micro-tensile bond testing, SEM- and, TEM-analysis. Data were analyzed using ANOVA and post hoc Tukey's HSD (p<0.05). RESULTS: In the control group (solely phosphoric acid), the mean microTBS was 53.4+/-10.6 MPa, which was, significantly higher than any hydrofluoric acid prepared group (group A versus groups B-E, p<0.001). No, significant differences in microTBS were found between the 3% and 9.6% hydrofluoric acid groups: group B versus group C (13.5+/-5.5 MPa and 18.7+/ 4.3 MPa, respectively) or group D versus group E (19.9+/-6.8 MPa and 20.3+/-4.1 MPa, respectively). SIGNIFICANCE: Due to its adverse effect on the bond strength of composite to dentin, contact of hydrofluoric acid to dentin should be avoided. PMID- 20359739 TI - Brief report: Development of the family perceptions scale; a novel instrument for evaluating subjective functioning in the families of adolescents. AB - A pool of 75 items relating to family functioning was created and piloted in a sample of 12-18 year olds (N = 673). The responses were subjected to an exploratory factor analysis which indicated the presence of three significant latent traits. The results were then used to inform the development of a rating instrument with five subscales labelled Nurture, Problem Solving, Expressed Emotion, Behavioural Boundaries and Responsibility. These demonstrated high levels of internal consistency (Cronbach's alphas .70-.81), high test-retest reliability (rho = .70-.82), varying degrees of intercorrelation (rho = .18-.75) and significant associations with family functioning as defined by the McMaster Family Assessment Device (p < 0.0001 in all cases). This novel instrument is a promising tool for use in both clinical practice and research. PMID- 20359740 TI - Brief report: Parsing the heterogeneity of adolescent girls' sexual behavior: relationships to individual and interpersonal factors. AB - Clusters of pre-sexual and sexual behaviors were identified in an urban US sample of 546 mid-adolescent girls. No distinct group of girls engaging in sexually risky behavior was revealed. Sexually active girls were older, lived with a single parent, and reported more substance use and depression, but similar levels of conduct problems, impulsivity and deviant peers to girls engaging in pre sexual behavior. PMID- 20359741 TI - Temporal variation of coastal surface sediment bacterial communities along an environmental pollution gradient. AB - Terminal restriction fragment length polymorphism analysis (T-RFLP) was used to track the changes of bacterial community compositions (BCC) in coastal surface sediments along an environmental pollution gradient between 2004 and 2006. BCC in the chronically contaminated sites showed the largest deviation from those in the adjacent sites. Surprisingly, BCC at two contrasting environments (oceanic vs. river-influenced) were more similar. Unexpectedly, the BCC did not recover (when compared to oceanic control site) even after 5 years of pollution abatement initiatives in Victoria Harbour, Hong Kong. On the other hand, disposal of treated sewage for 5 years in one of the sites did not significantly affect the BCC. A striking seasonal variation in the BCC was observed at only the polluted sites. Although factors other than pollution gradients may explain the observed BCC patterns, the information presented here can be useful in predicting long term effects of pollution on BCC. Furthermore, this study suggests that BCC analysis using T-RFLP is a faster, reliable and easier approach to monitor microbenthic community response to environmental pollution gradient in coastal sediments. PMID- 20359742 TI - The incorporation of GALA peptide into a protein cage for an acid-inducible molecular switch. AB - Caged proteins have been utilized as a biological container in a wide range of applications from material science to biomedicine, and GALA peptide has been known to undergo coil-to-helix transition upon the increased acidity. In this study, GALA synthetic peptide is incorporated to cage protein by genetic modification. Our engineered caged scaffold retains intact at the physiological pH but dissociate completely at pH 6.0, and the dissociated subunits are re assembled simply by neutralization to biological pH. This acid-induced dissociation has the potential as molecular switch in vivo as well as in vitro so that the acid-sensitive caged proteins are applicable to drug delivery system for acidic target sites such as tumor. Since our design depends on the conformational transition of GALA peptide, not on removal of characteristic interface observed only in viral capsid-like protein, non-viral caged proteins can also be engineered to have molecular switching function. Therefore, this design for acid sensitive scaffold would broaden the width of applications in nanotechnology including biomimetic material synthesis and biomedicine. PMID- 20359743 TI - Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field. AB - A number of important changes take place in the maternal uterine vasculature during the first few weeks of pregnancy resulting in increased blood flow to the intervillous space. Vascular endothelial and smooth muscle cells are lost from the spiral arteries and are replaced by fetal trophoblast cells. Failure of the vessels to remodel sufficiently is a common feature of pregnancy pathologies such as early pregnancy loss, intrauterine growth restriction and pre-eclampsia. There is evidence to suggest that some vascular changes occur prior to trophoblast invasion, however, in the absence of trophoblasts remodelling of the spiral arteries is reduced. Until recently our knowledge of these events has been obtained from immunohistochemical studies which, although extremely useful, can give little insight into the mechanisms involved. With the development of more complex in vitro models a picture of events at a cellular and molecular level is beginning to emerge, although some caution is required in extrapolating to the in vivo situation. Trophoblasts synthesise and release a plethora of cytokines and growth factors including members of the tumour necrosis factor family. Studies suggest that these factors may be important in regulating the remodelling process by inducing both endothelial and vascular smooth muscle cell apoptosis. In addition, it is evident from studies in other vascular beds that the structure of the vessel is influenced by factors such as flow, changes in the composition of the extracellular matrix, the phenotype of the vascular cells and the local immune cell environment. It is the aim of this review to present our current knowledge of the mechanisms involved in spiral artery remodelling and explore other possible pathways and cellular interactions that may be involved, informed by studies in the cardiovascular field. PMID- 20359744 TI - Testicular cancer developed in a chronic myeloid leukemia patient with a continued complete cytogenetic and molecular response to imatinib. A case report and review of the literature. PMID- 20359745 TI - Immunogenic antigens as therapeutic targets against myeloid leukaemic cells. AB - SPAG9 is a further new antigen that might be a candidate for clinical use. In particular the high frequency of mRNA expression in different solid tumours and haematological malignancies is a prerequisite for a potentially wide use. Most of the tested CML patients showed humoral immune responses against SPAG9. Nevertheless, specific CD8-positive T cell-responses and clinical efficacy analogue to the targets RHAMM or WT-1 have to be shown. PMID- 20359746 TI - Clinical categories identified by a new prognostic index reflect biological characteristics of patients in early chronic lymphocytic leukemia: The Gruppo Italiano Studio Linfomi (GISL) experience. PMID- 20359747 TI - The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. AB - Bcl-2 family proteins have long been implicated in the pathology of chronic lymphocytic leukaemia (CLL). Indeed, a number of these proteins have been shown to have prognostic importance in this disease. The precise ways in which these proteins impact upon CLL and the ways in which they are regulated remain incompletely resolved. However, significant advances have been recently made in our understanding of how these proteins are controlled by genetic, epigenetic and microenvironmental cues. Furthermore, major progress has been made in trying to target these proteins therapeutically. Here we review the current knowledge about this family of apoptosis-regulating proteins and how they impact upon drug resistance and disease progression. We also summarise evolution in the development of Bcl-2 family inhibitors for the treatment of CLL and other cancers. PMID- 20359748 TI - Do trauma symptoms mediate the relationship between childhood physical abuse and adult child abuse risk? AB - OBJECTIVE: Although the intergenerational transmission of family violence has been well documented, the mechanisms responsible for this effect have not been fully determined. The present study examined whether trauma symptoms mediate the relationship between a childhood history of child physical abuse (CPA) and adult CPA risk, and whether any such mediation was similar for women and men. METHOD: Female and male US Navy (USN) recruits (N=5,394) and college students (N=716) completed self-report measures of their history of child abuse (i.e., CPA and child sexual abuse [CSA]), exposure to intimate partner violence (IPV), current trauma symptoms, and adult CPA risk. RESULTS: As expected, there was a strong association between a childhood history of CPA and adult CPA risk. This association was significant even after controlling for demographic variables and childhood exposure to other forms of violence (CSA and IPV), and the strength of the relationship did not vary depending on demographics or exposure to other forms of violence. However, the association between a history of CPA and adult risk of CPA was stronger for individuals high in defensive avoidance compared to those low in defensive avoidance. The association between a history of CPA and adult CPA risk was largely, although not entirely, mediated by psychological trauma symptoms. Mediation was observed for both women and men in both the USN and college samples. CONCLUSIONS: Trauma symptoms associated with a history of CPA accounted for a substantial part of the relationship between a history of CPA and adult CPA risk in both women and men. PRACTICE IMPLICATIONS: To the extent that trauma symptoms are a mechanism by which the intergenerational transmission of child abuse occurs, intervening to reduce trauma symptoms in CPA victims has the potential of reducing their risk of continuing the cycle of violence. PMID- 20359749 TI - Childhood sexual abuse in males and subsequent risky sexual behavior: a potential alcohol-use pathway. AB - OBJECTIVE: Childhood sexual abuse (CSA) among boys has been associated with a variety of subsequent maladaptive behaviors. This study explored a potential connection between CSA and an increased likelihood of risky sexual behavior in adulthood. Further, the study examined whether or not alcohol use may contribute to this relationship. METHOD: As part of a study on alcohol and sexual decision making, 280 heterosexual men completed multiple background questionnaires pertaining to past and current sexual experiences and patterns of alcohol use. CSA history was obtained and severity ratings were made based on type of contact reported. RESULTS: CSA was reported by 56 men (20%). Structural equation modeling revealed that CSA positively predicted number of sexual partners directly as well as indirectly, through its effect on alcohol use. Specifically, greater CSA severity predicted significantly lower age of first intoxication, which in turn predicted greater current alcohol consumption, followed by greater use of alcohol before sexual intercourse, leading to an increased number of reported sexual partners. The reported frequency of condom use was not predicted by CSA severity or the alcohol-use pathway. CONCLUSIONS: These findings suggest that CSA influences risky sexual behavior via multiple pathways and that more severe CSA may lead to elevated sexual risk indices. Moreover, these results suggest that men may elevate their risk of sexually transmitted infections via high numbers of sexual partners versus irregular condom use. PRACTICAL IMPLICATIONS: These results highlight the need for adequate assessment and early interventions in order to mitigate the effects CSA may have on subsequent alcohol use and risky sexual behavior. Secondly, ensuring that male CSA victims understand the inherent risks of high numbers of sexual partners may be an effective strategy to interrupt the path toward risk-taking. PMID- 20359750 TI - Neurodevelopmental and psychological assessment of adolescents born to drug addicted parents: effects of SES and adoption. AB - OBJECTIVES: Prenatal exposure to heroin may have long-term consequences for development during early and middle childhood. The present research studied the cognitive, social, and emotional functioning of adolescents exposed to drugs prenatally, and investigated the extent to which the early adoption of children exposed prenatally to drugs would alleviate the possible effects of exposure. METHODS: The study included 191 adolescents (12-16 years of age) and their parents in Israel, who had or had not been exposed prenatally to drugs and differing in socio-economic status (SES), and in adoptive status. They were administered five subtests of the Wechsler Intelligence Scale for Children (WISC III), and the Youth Self-Report Form for assessing behavior problems that measures problems associated with attention deficit, self-esteem and risk-taking. Parents were administered the Child Behavior Checklist (CBCL) for assessing behavior problems, the Conners Rating Scale (CRS) for assessing attention deficit problems in their children and the Wender Utah Rating Scale (WURS), a self-report measure of ADHD-related problems. RESULTS: Adolescents exposed to at least one risk factor (exposure to drugs, low SES, or adoption) performed more poorly than those exposed to none of these risk factors on the WISC-III subtests, the CBCL and the CRS. The effects of risk factors did not cumulate. Contrary to our hypothesis, adoption did not mitigate the effects of prenatal exposure to drugs: for cognitive functioning exposure to drugs was associated with poorer performance among the exposed High SES Adopted versus non-exposed High SES non adopted children on three of the WISC-III subtests. Exposed low SES children living with their parents performed at the same relatively low level as non exposed low SES controls. Exposure to drugs was associated with adult ADHD related problems assessed by the WURS. There were no direct or interaction effects of exposure on neurological functioning, self-competence, behavior problems on the CBCL or risk-taking. CONCLUSIONS: Children exposed to drugs of abuse prenatally, including those adopted away, and children who grow up in low SES backgrounds, may be at risk of relatively reduced cognitive functioning (though still within the normal range) in adolescence. Children exposed to drugs, who are from low SES backgrounds, or who are adopted, may be at risk for lower cognitive or social functioning than children who have not experienced such risks. PRACTICE IMPLICATIONS: There is a need for implementing early monitoring and long-term intervention programs featuring encouragement of cognitive and social skills for children prenatally exposed to drugs in order to alleviate the possible long-term effects of exposure to risk. PMID- 20359751 TI - The association of exon 3 VNTR polymorphism of the dopamine receptor D4 (DRD4) gene with alcoholism in Mexican Americans. AB - In this study, the variable number tandem repeats (VNTR) polymorphism of a 48-bp sequence located in exon 3 of the dopamine receptor D4 (DRD4) gene was genotyped in 365 alcoholic and 337 non-alcoholic Mexican Americans. Logistic regression showed that genotypes without the 7-repeat allele were risk factors for alcoholism. However, linear regression did not find an association between DRD4 VNTR and MAXDRINKS, which was defined as the maximum number of drinks consumed within 24h. Our results indicate the presence of an association between DRD4 VNTR and alcoholism in Mexican Americans. PMID- 20359752 TI - Bluetongue virus infection activates bovine monocyte-derived macrophages and pulmonary artery endothelial cells. AB - Bluetongue virus (BTV) is the cause of bluetongue (BT), an emerging, arthropod transmitted disease of ungulates. The cellular tropism of BTV in ruminants includes macrophages, dendritic cells and endothelial cells (ECs), and fulminant infection is characterized by lesions consistent with those of so-called viral hemorrhagic fevers. Specifically, BT is characterized by vascular injury with hemorrhage, tissue infarction and widespread edema. To further investigate the pathogenesis of vascular injury in BT, we evaluated the responses of cultured bovine pulmonary artery EC (bPAEC) and monocyte-derived macrophages (bMDM) to BTV infection by measuring transcript levels of genes encoding molecules important in mediating EC activation and/or endothelial barrier dysregulation. The data confirm that BTV infection of bPAEC resulted in increased transcription of genes encoding chemokine ligand 2 (CCL2) and E-selectin, and BTV infection of bMDM resulted in increased transcription of genes encoding TNF-alpha, IL-1beta, IL-8, and inducible nitric oxide synthase (iNOS). The data from these in vitro studies provide further evidence that cytokines and other vasoactive substances produced in macrophages potentially contribute to vascular injury in BTV-infected ruminants, along with direct effects of the virus itself on ECs. PMID- 20359753 TI - Bluetongue virus infection alters the impedance of monolayers of bovine endothelial cells as a result of cell death. AB - Bluetongue virus (BTV) is the cause of bluetongue, an emerging, arthropod transmitted disease of ungulates. Bluetongue is characterized by vascular injury with hemorrhage, tissue infarction and widespread edema, lesions that are consistent with those of the so-called viral hemorrhagic fevers. To further investigate the pathogenesis of vascular injury in bluetongue, we utilized an electrical impedance assay and immunofluorescence staining to compare the effects of BTV infection on cultured bovine endothelial cells (bPAEC) with those of inducers of cell death (Triton X-100) and interendothelial gap formation (tissue necrosis factor [TNF]). The data confirm that the adherens junctions of BTV infected bPAECs remained intact until 24h post-infection, and that loss of monolayer impedance precisely coincided with onset of virus-induced cell death. In contrast, recombinant bovine TNF-alpha caused rapid loss of bPAEC monolayer impedance that was associated with interendothelial gap formation and redistribution of VE-cadherin, but without early cell death. The data from these in vitro studies are consistent with a pathogenesis of bluetongue that involves virus-induced vascular injury leading to thrombosis, hemorrhage and tissue necrosis. However, the contribution of cytokine-induced interendothelial gap formation with subsequent edema and hypovolemic shock contributes to the pathogenesis of bluetongue remains to be fully characterized. PMID- 20359754 TI - Lipoxygenase metabolites modulate vascular-derived platelet activating factor production following endotoxin challenge. AB - Endotoxin promotes the production of potent pro-inflammatory lipid mediators, such as platelet activating factor (PAF) and eicosanoids, which contribute to the pathophysiology of endotoxic shock. Endothelial cells are both a target for and producers of these lipid mediators so it is vital to understand the pathways leading to their production in these cells. Previous research suggested a positive feedback loop between eicosanoids and PAF during endotoxemia. This study sought to determine if eicosanoids derived from the 15-lipoxygenase (15-LOX1) pathway can modulate the biosynthesis of PAF in cultured bovine aortic endothelial cells (BAEC) following endotoxin stimulation. Endotoxin stimulation increased the production of 15-LOX1-derived eicosanoids prior to PAF in primary BAEC. Exogenous addition of specific 15-LOX1 eicosanoids, as well as overexpression of 15-LOX1 in endotoxin-stimulated BAEC, further increased the endotoxin-induced production of PAF. Whereas increased expression of 15-LOX1 activity can further exacerbate endotoxin-induced PAF biosynthesis, inhibition of 15-LOX1 activity is not capable of abrogating the initial onset of endotoxin induced PAF production. The results indicate that 15-LOX1 activity is not necessary for the initial induction of PAF following endotoxin stimulation. There may exist, however, a role for elevated 15-LOX1 activity in further escalating the extent of PAF biosynthesis in BAEC during endotoxic shock. Determining factors that can potentiate endotoxin-induced vascular dysfunction may lead to the development of novel therapeutic targets to diminish the pathophysiological effects of endotoxic shock. PMID- 20359755 TI - Evaluation of musical skills in children with a diagnosis of an auditory processing disorder. AB - Impaired musical skills are reported in parental questionnaires to be present in children with an auditory processing disorder (APD). OBJECTIVES: To formally assess musical skills in children with a diagnosis of APD. METHODS: We used a validated musical test battery with extensive normative pediatric data, the Gordon's Musical Aptitude Profile and the tests of metre and melody in particular, in order to assess the musical skills of 8 children with a previously given diagnosis of APD (APD group) and 8 normal controls (control group) aged 7 15 years old. The two groups were well matched for age, sex, handedness, socio economic factors and musical training. RESULTS: The APD group had significantly lower metre percentile scores than normal children (mean difference 28.9, p=0.003). Melody scores tended to be lower in the APD group than in the controls, but this did not reach significance, possibly due to low power of the study. CONCLUSION: This is the first study that systematically assesses musical skills in children with a formal diagnosis of APD in the absence of other developmental disorders. The APD group did significantly worse than the control group in judging metre. Musical skills assessment in children with APD may help constrain our understanding of this heterogeneous condition and possibly inform the management plan for these children. PMID- 20359756 TI - Behavioural problems in young children with language problems. AB - OBJECTIVE: Analysis of behavioural problems in young children with language problems. MATERIALS AND METHODS: From 38 children diagnosed with a language problem, the opinion of the parents about the behaviour of their child, scored by the Child Behaviour Checklist 1.5-5 was compared with the behavioural problems in the Dutch population with the Chi-square test. T-tests and Mc Nemar tests were used to compare the opinion of the fathers about the behavioural problems with the opinion of the mothers and to compare the scores on internalizing problems with scores on externalizing problems. Plots display the measurement of the mean behavioural problems of the parents against the discrepancy between the parents and of the total behavioural problems against the discrepancy between internalizing and externalizing problems. The relation between the behavioural problems, the language score and the non-verbal intelligence score was also compared and is presented in a bar chart. RESULTS: All children had an inadequate language production (GDS). Twenty-seven children had an adequate and 11 children had an inadequate Language Comprehension Quotient (LCQ). Twenty-eight children had an adequate and 10 children had an inadequate non-verbal IQ (SON-IQ). In the clinical population mothers report more internalizing behavioural problems than in Dutch peers. The fathers also experience differences, but these are not significant. There is agreement between the parents in how they experience problems on the internalizing, externalizing and total problem scale. And there are no significant differences between the internalizing and externalizing problem scales, between boys and girls, and in behavioural problems in children with both adequate LCQ and SON-IQ and with inadequate LCQ and/or SON-IQ. CONCLUSION: Compared to their peers in the Dutch population, young children with language problems show more internalizing problems according to their mothers. The fathers also experience differences, but these are not significant. Fathers and mothers agree on the behaviour analysis of their child and there are no differences between the occurrences of internalizing or externalizing problems and between boys and girls. There is also no relation between the behavioural problems and the severity of the language problem or the level of non-verbal functioning. PMID- 20359757 TI - A transcriptomics-based biological framework for studying mechanisms of endocrine disruption in small fish species. AB - This study sought to construct a transcriptomics-based framework of signal transduction pathways, transcriptional regulatory networks, and the hypothalamic pituitary gonadal (HPG) axis in zebrafish (Danio rerio) to facilitate formulation of specific, testable hypotheses regarding the mechanisms of endocrine disruption in fish. For the analyses involved, we used data from a total of more than 300 microarrays representing 58 conditions, which encompassed 4 tissue types from zebrafish of both genders exposed for 1 of 3 durations to 10 different test chemicals (17alpha-ethynyl estradiol, fadrozole, 17beta-trenbolone, fipronil, prochloraz, flutamide, muscimol, ketoconazole, trilostane, and vinclozolin). Differentially expressed genes were identified by one class t-tests for each condition, and those with false discovery rates of less than 40% and treatment/control ratios > or =1.3-fold were mapped to orthologous human, mouse, and rat pathways by Ingenuity Pathway Analysis to look for overrepresentation of known biological pathways. To complement the analysis of known biological pathways, the genes regulated by approximately 1800 transcription factors were inferred using the ARACNE mutual information-based algorithm. The resulting gene sets for all transcriptional factors, along with a group of compiled HPG-axis genes and approximately 130 publicly available biological pathways, were analyzed for their responses to the 58 treatment conditions by Gene Set Enrichment Analysis (GSEA) and its variant, Extended-GSEA. The biological pathways and transcription factors associated with multiple distinct treatments showed substantial interactions among the HPG-axis, TGF-beta, p53, and several of their cross-talking partners. These candidate networks/pathways have a variety of profound impacts on such cellular functions as stress response, cell cycle, and apoptosis. PMID- 20359758 TI - Spatial and temporal clustering of calcium oxalate and magnesium ammonium phosphate uroliths in dogs living in Ontario, Canada between 1998 and 2006. AB - Using the spatial scan statistic with a Bernoulli model, in a comparison of the two most common canine uroliths, calcium oxalate (CaOx) and magnesium ammonium phosphate (struvite) we determined whether there was evidence of spatial and/or temporal clustering of each urolith type based on canine submissions from Ontario to the Canadian Veterinary Urolith Centre (CVUC) between 1998 and 2006. During this period, there were 10,478 canine submissions, excluding cases that were identified as recurrent. We were able to georeference approximately 93% of these incident cases. After adjusting for spatial and temporal distributions of dogs based on the demographic risk factors of age, sex, and breed-type, statistically significant spatial and temporal clusters were present for both CaOx and struvite urolith types. A purely temporal struvite cluster occurred between February 10, 1998 and December 20, 2001, whereas, a purely temporal CaOx cluster occurred between September 2, 2005 and December 21, 2006. Hypotheses to explain the spatial clustering of uroliths include variation in the spatial distribution of water hardness, diet-type, access to veterinary care, and the use of surgical versus medical therapies to treat these uroliths. Based on the cluster locations, water hardness was unlikely to explain the spatial difference between the two cluster types whereas variables related to human population density were more consistent with our findings; the CaOx cluster occurred in the highest population density area of Ontario, and the struvite cluster occurred in the lowest population density area of southern Ontario. The temporal struvite cluster at the beginning and CaOx cluster at the end of the study period reflect a similar trend away from struvite towards CaOx urolithiasis among both canines and humans in the developed countries of North America and Europe. PMID- 20359759 TI - The effect of children on adult demands for health-risk reductions. AB - We examine patterns in adults' willingness to pay for health-risk reductions. We allow both their marginal utilities of income and their marginal disutilities from health risks to vary systematically with the structures of their households. Demand by adults for programs which reduce their own health risks is found to be influenced by (1) their parenthood status, (2) the numbers of children in different age brackets currently in their households, (3) the ages of the adults themselves, (4) the latency period before they would fall ill, and (5) whether there will still be children in the household at that time. For younger adults, willingness to pay by parents is greater than for non-parents, and increases with each additional young child. For middle-aged adults, willingness to pay for corresponding risk reductions falls when teenagers are present and falls further with each additional teenager in the household. PMID- 20359760 TI - The role of education in the production of health: an empirical analysis of smoking behavior. AB - We estimate the effect of education on smoking. Our estimation strategy "differences out" the impact of unobserved characteristics correlated with education by exploiting education differences between similarly selected groups 1 year apart in their life cycle. Individuals with a given age, education, and student status in the current and previous year are compared to their counterparts born 1 year later with the same age, education, and student status in the following and current year. We find that an additional year of education does not have a causal effect on smoking. Unobserved factors correlated with education entirely explain their cross-sectional relationship. PMID- 20359761 TI - The potential role of self-cleaving purification tags in commercial-scale processes. AB - Purification tags are robust tools that can be used to purify a wide selection of target proteins, which makes them attractive candidates for implementation into platform processes. However, tag removal remains an expensive and significant issue that must be resolved before these tags can become widely used. One alternative is self-cleaving purification tags, which can provide the purity and versatility of conventional tags but eliminate the need for proteolytic tag removal. Many of these self-cleaving tags are based on inteins, but other emerging technologies, such as the FrpC and SrtAc proteins, have also been reported. In this review, we cover affinity and non-chromatographic self-cleaving purification tags and their potential industrial applications. PMID- 20359762 TI - Proteomics in clinical chemistry: will it be long? AB - Proteomics has stimulated the development of very powerful methods for protein analysis. Implementation of some of these methods in clinical chemistry laboratories could offer clinicians better tools for diagnosis, prognosis and therapeutic follow-up of human diseases. However, laboratory medicine activities are bound by a number of constraints and rules for ensuring quality of results for clinical practice. There is therefore a gap to be filled between the research and routine medical laboratories. In this opinion article, we present the proteomic methods that will most likely be implemented in clinical chemistry laboratories in the short term, and we discuss the major issues yet to be addressed before considering such a transfer. PMID- 20359763 TI - Individual differences in the visual control of intercepting a penalty kick in association football. AB - Recent perceptual-motor studies have revealed variations in learning trajectories of novices. Despite such observation, relatively little attention has been paid to studying individual differences in experienced performers' perceptual-motor behaviors. The present study examined individual differences for a visual anticipation task. Experienced association football goalkeepers attempted to intercept penalty kicks taken with deceptive and non-deceptive kicking actions. Data revealed that differences in the action capabilities of goalkeepers affected the timing and accuracy of movement response behaviors. Faster goalkeepers tended to wait until later before initiating movement in comparison with slower goalkeepers. The study of affordances in sport environments offers a theoretical framework with which to overcome some of the reported methodological limitations in the visual anticipation literature. PMID- 20359764 TI - Influences of simultaneous physicochemical stress exposures on injury and subsequent responses of E. coli O157:H7 to resuscitative and inactivative challenges. AB - E. coli O157:H7 responses namely, sublethal injury (% injury), subsequent resuscitation (lag) and growth parameters (k(G) and max population), and inactivation rates (D(25) and D(55)) were investigated following exposures to simultaneous pH (3.0-8.0), a(w) (0.93-0.99) and temperature stresses (3.0-62 degrees C). Multiple regression analyses showed that % injury was significantly influenced by a(w), a(w)(2), and temperature while the lag times were influenced by pH, pH-temperature interaction, and a(w)-temperature interaction. The measured growth parameters were however, not significantly influenced by any of the stressors. Acid inactivation rates (D(25)) in apple juice were influenced by a(w), pH-temperature interaction, and a(w)-temperature interaction; while the thermal inactivation rates (D(55)) in apple juice were influenced by pH and a(w) stresses. Results also showed that % injury alone may not correctly predict the subsequent resuscitation rates of the test organism at favorable growth conditions. The nature of the injury contributed by a specific stressor also influenced resuscitation. The occurrence of injury and loss of cell viability did not induce acid stress adaptation to the organism. However, exposures to very low and low pH conditions that resulted in injury and loss in cell viability induced thermal cross protection in E. coli O157:H7. The results obtained in the study contribute in further understanding the behavior of the test organism after exposure to combinations of stresses commonly encountered in food and food processing ecologies. PMID- 20359765 TI - High prevalence of diabetic neuropathy in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown. AB - AIMS: To determine the prevalence of diabetic peripheral neuropathy (DPN) and risk factors associated with DPN in type 2 diabetic patients. METHODS: 435 diabetic patients were evaluated on complete foot examination. Body mass measurements, resting blood pressure, fasting blood measures, urinary albumin-to creatinine ratio (ACR) and the digitally stored fundus images were investigated. RESULTS: (1) The prevalence of DPN was 61.8% among the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown, 59.1% with vibration perception threshold > or =25 V and 13.8% with inability to feel the monofilament. (2) DPN was significantly associated with age (beta: 0.068, S.E.: 0.013, OR: 1.070, CI: 1.043-1.098, P<0.001) and HbA1c (beta: 0.224, S.E.: 0.081, OR: 1.251, CI: 1.067-1.466, P=0.006) by a logistic regression analysis. (3) The percentage of diabetic retinopathy (DR) in the DPN group (26.5%) was significantly higher than that in the non-DPN group (15.2%). (4) The percentage of macroalbuminuria in the DPN group (9.0%) was significantly higher than that in the non-DPN group (1.8%). CONCLUSIONS: The prevalence of DPN observed in the Chinese patients diagnosed with type 2 diabetes aged over 30 in the Shanghai downtown reached up to 61.8% though the observations in our study might be representative of the diabetic patients of the Shanghai downtown. PMID- 20359766 TI - Patterns of health care use and expenditure during the last 6 months of life in Belgium: differences between age categories in cancer and non-cancer patients. AB - OBJECTIVES: We analysed end-of-life care in Belgium to examine potential age variation in place of death, transitions between care settings, health care utilisation and public expenditure in the last 6 months of life. METHODS: Administrative data of one sickness fund were used, and analysed through regression analysis and analysis of variance. The study population comprised 40,794 individuals (age>40 years). RESULTS: Several indicators showed that the end-of-life of older people, especially of those aged >or=90 years, differs from that of younger individuals. Older persons more likely died in a care home, were less transferred between care settings, and stayed less days in hospital. On the other hand, older persons used more home care services, and had more contacts with the general practitioner. Differences between age categories were equally observed for last week's end-of-life care. Opposite to the trend for cancer patients, the odds of having a palliative home care allowance increased with age for non-cancer patients. Public expenditure for the oldest old was lower as compared to the younger decedents, but dependent on place of death. CONCLUSION: Several aspects of end-of-life care in Belgium appear to be influenced by age. In view of ageing of the population, these findings can be of interest to decision makers. PMID- 20359767 TI - Automated segmentation of tissue images for computerized IHC analysis. AB - This paper presents two automated methods for the segmentation of immunohistochemical tissue images that overcome the limitations of the manual approach as well as of the existing computerized techniques. The first independent method, based on unsupervised color clustering, recognizes automatically the target cancerous areas in the specimen and disregards the stroma; the second method, based on colors separation and morphological processing, exploits automated segmentation of the nuclear membranes of the cancerous cells. Extensive experimental results on real tissue images demonstrate the accuracy of our techniques compared to manual segmentations; additional experiments show that our techniques are more effective in immunohistochemical images than popular approaches based on supervised learning or active contours. The proposed procedure can be exploited for any applications that require tissues and cells exploration and to perform reliable and standardized measures of the activity of specific proteins involved in multi-factorial genetic pathologies. PMID- 20359768 TI - Hospital outbreak control requires joint efforts from hospital management, microbiology and infection control. AB - An outbreak of multidrug-resistant Klebsiella pneumoniae producing the extended spectrum beta-lactamase CTX-M15 affected 247 mainly elderly patients in more than 30 wards in a 1000-bedded swedish teaching hospital between May 2005 and August 2007. A manual search of the hospital administrative records for possible contacts between cases in wards and outpatient settings revealed a complex chain of transmission. Faecal screening identified twice as many cases as cultures from clinical samples. Transmission occurred by direct and indirect patient-to-patient contact, facilitated by patient overcrowding. Interventions included formation of a steering group with economic power, increased bed numbers, better compliance with alcohol hand disinfection and hospital dress code, better hand hygiene for patients and improved cleaning. The cost of the interventions was estimated to be euro3 million. Special infection control policies were not necessary, but resources were needed to make existing policies possible to follow, and for educational efforts to improve compliance. PMID- 20359769 TI - A randomised controlled pilot study to compare filtration factor of a novel non fit-tested high-efficiency particulate air (HEPA) filtering facemask with a fit tested N95 mask. AB - Use of a fit-tested N95 or FFP2 mask is recommended to protect against transmission of airborne pathogens. This poses considerable logistic problems when preparing for, or dealing with, an epidemic. Some of these problems might be overcome by use of a compact reusable high-efficiency particulate air filtering mask that can be cut to size. We carried out a randomised controlled cross-over study to compare the efficacy of such a mask (Totobobo, Dream Lab One Pte Ltd, Singapore) with fit-tested N95 masks (1860 or 1860s or 1862; 3M, St Paul, MN, USA) in 22 healthy volunteers. The median (interquartile range) reduction in airborne particle counts was significantly higher [193-fold (145-200)] for N95 masks than for Totobobo masks [135-fold (83-184)] (P<0.05). There was no statistically significant difference between the proportion of subjects achieving a reduction of > or =100-fold between N95 (19/22) and Totobobo (16/22) masks. We conclude that use of the Totobobo mask without fit testing cannot be recommended, but its performance is sufficiently promising to warrant further investigation. PMID- 20359770 TI - Potential virulence factors of Candida spp. isolated from clinical and food sources. PMID- 20359771 TI - Improved out-of-hospital cardiac arrest survival after the sequential implementation of 2005 AHA guidelines for compressions, ventilations, and induced hypothermia: the Wake County experience. AB - STUDY OBJECTIVE: We assess survival from out-of-hospital cardiac arrest after community-wide implementation of 2005 American Heart Association guidelines. METHODS: This was an observational multiphase before-after cohort in an urban/suburban community (population 840,000) with existing advanced life support. Included were all adults treated for cardiac arrest by emergency responders. Excluded were patients younger than 16 years and trauma patients. Intervention phases in months were baseline 16; phase 1, new cardiopulmonary resuscitation 12; phase 2, impedance threshold device 6; and phase 3, full implementation including out-of-hospital-induced hypothermia 12. Primary outcome was survival to discharge. Other survival and neurologic outcomes were compared between study phases, and adjusted odds ratios with 95% confidence intervals (CIs) for survival by phase were determined by multivariate regression. RESULTS: One thousand three hundred sixty-five cardiac arrest patients were eligible for inclusion: baseline n=425, phase 1 n=369, phase 2 n=161, phase 3 n=410. Across phases, patients had similar demographic, clinical, and emergency medical services characteristics. Overall and witnessed ventricular fibrillation and ventricular tachycardia survival improved throughout the study phases: respectively, baseline 4.2% and 13.8%, phase 1 7.3% and 23.9%, phase 2 8.1% and 34.6%, and phase 3 11.5% and 40.8%. The absolute increase for overall survival from baseline to full implementation was 7.3% (95% CI 3.7% to 10.9%); witnessed ventricular fibrillation/ventricular tachycardia survival was 27.0% (95% CI 13.6% to 40.4%), representing an additional 25 lives saved annually in this community. CONCLUSION: In the context of a community-wide focus on resuscitation, the sequential implementation of 2005 American Heart Association guidelines for compressions, ventilations, and induced hypothermia significantly improved survival after cardiac arrest. Further study is required to clarify the relative contribution of each intervention to improved survival outcomes. PMID- 20359772 TI - The application of mechanical devices for CPR: make the first 5 minutes the best 5 minutes! PMID- 20359773 TI - Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. AB - Diabetes is a risk factor for Alzheimer's disease. We tested the effects of Val(8)GLP-1, an enzyme-resistant analogue of the incretin hormone glucagon-like peptide 1 originally developed to treat diabetes in a mouse model of Alzheimer's disease that expresses mutated amyloid precursor protein (APP) and presenilin-1. We tested long term potentiation (LTP) of synaptic plasticity, inflammation response, and plaque formation. Val(8)GLP-1 crosses the blood-brain barrier when administered via intraperitoneal injection. Val(8)GLP-1 protected LTP in 9- and 18-month-old Alzheimer's disease mice when given for 3 weeks at 25 nmol/kg intraperitoneally. LTP was also enhanced in 18-month-old wild type mice, indicating that Val(8)GLP-1 also ameliorates age-related synaptic degenerative processes. Paired-pulse facilitation was also enhanced. The number of beta amyloid plaques and microglia activation in the cortex increased with age but was not reduced by Val(8)GLP-1. In 18-month-old mice, however, the number of Congo red positive dense-core amyloid plaques was reduced. Treatment with Val(8)GLP-1 might prevent or delay neurodegenerative processes. PMID- 20359774 TI - Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice. AB - Environmental enrichment has been used in a variety of transgenic mouse models of Alzheimer's disease (AD), however, with conflicting results. Here we studied the influence of environmental enrichment in a severely affected AD mouse model, showing a multiplicity of pathological alterations including hippocampal neuron loss. APP/PS1KI and wild type (WT) control mice were housed under standard conditions or in enriched cages equipped with various objects and running wheels. Amyloid plaque load, motor and working memory performance, axonopathy, as well as CA1 neuron number and hippocampal neurogenesis were assessed. Although a partial improvement in motor performance was observed, 4 months of enriched housing showed no beneficial effects in terms of working memory, Abeta plaque pathology, or neuron loss in APP/PS1KI mice. In addition, no changes in hippocampal neurogenesis and even an aggravation of the axonal phenotype were detected with a tendency toward a premature death. The APP/PS1KI model represents a model for mild to severe AD showing early behavioral deficits starting at 2 months of age with fast deterioration. Therefore our data might suggest that physical activity and enriched environment might be more beneficial in patients with mild cognitive impairment than in patients with incipient AD. PMID- 20359775 TI - Hypermetabolism in a triple-transgenic mouse model of Alzheimer's disease. AB - A common feature of Alzheimer's disease (AD) is weight loss, even though there is often an increase in food intake in AD patients. The reasons for this weight loss are unknown, but may be due to increased energy expenditure (metabolic rate) or a reduction in energy intake. This was investigated in the present study, using a triple-transgenic (3xTgAD) mouse model of AD. Two-month-old 3xTgAD mice displayed greater food intake (17%) and body weight (34%) but no difference in metabolic rate, as compared with nontransgenic controls (non-Tg). At 12 months of age, 3xTgAD mice still consumed more food (30%), but their body weight was significantly lower (15%) than non-Tg controls. This reduction in body weight was accompanied by a significant rise in metabolic rate, indicated by greater oxygen consumption (24%) and carbon dioxide production (29%); the effects were also observed in 18-month-old 3xTgAD mice. These data demonstrate for the first time the existence of a hypermetabolic state in an experimental model of AD, but whether this can explain the weight loss observed in AD patients remains to be determined. PMID- 20359776 TI - MRI predictors of cognitive change in a diverse and carefully characterized elderly population. AB - BACKGROUND: Trajectories of cognitive decline among elderly individuals are heterogeneous, and markers that have high reliability for predicting cognitive trajectories across a broad spectrum of the elderly population have yet to be identified. METHOD: This study examined the utility of a variety of MRI-based brain measures, obtained at baseline, as predictors of subsequent declines in domain-specific measures of cognitive function in a cohort of 307 community dwelling elderly individuals with varying degrees of cognitive impairment who were diverse across several relevant demographic variables and were evaluated yearly. Psychometrically matched measures of cognition were used to assess episodic memory, semantic memory, and executive function. Relationships between baseline MRI measures, including the volumes of the brain, hippocampus, and white matter hyperintensities (WMH), and cognitive trajectories were assessed in mixed effects regression models that modeled MRI effects on cognitive performance at baseline and rate of change as well as interindividual variability in cognitive baseline and rate of change. RESULTS: Greater baseline brain volume predicted slower subsequent rate of decline in episodic memory and smaller WMH volume predicted slower subsequent rate of decline in executive function and semantic memory. Baseline hippocampal volume, while strongly related to baseline cognitive function, was not predictive of subsequent change in any of the cognitive domains. CONCLUSIONS: Baseline measures of brain structure and tissue pathology predicted rate of cognitive decline in a diverse and carefully characterized cohort, suggesting that they may provide summary measures of pre-existing neuropathological damage or the capacity of the brain to compensate for the impact of subsequent neuropathology on cognition. Conventional MRI measures may have use for predicting cognitive outcomes in highly heterogeneous elderly populations. PMID- 20359777 TI - Increased tissue factor pathway inhibitor and homocysteine in Alzheimer's disease. AB - We investigated the possible involvement of vascular damage in the pathogenesis of Alzheimer's disease (AD), by assessment of plasma levels of tissue factor pathway inhibitor (TFPI), a serine protease inhibitor induced by endothelial injury, and homocysteine (Hcy), a known risk factor for cerebrovascular disorders, folate levels were also measured. 110 probable AD, 38 mild cognitive impairment, 31 patients affected by idiopathic Parkinson's disease (without dementia) and 100 healthy controls, who displayed no vascular disorders were enrolled. TFPI and Hcy were significantly higher in AD patients with respect to other groups. The levels of TFPI and Hcy were positively correlated in hyperhomocysteinemic AD and mild cognitive impairment subjects, and were negatively correlated with folate levels. Our findings suggest that an impairment of endothelial function associated with high Hcy levels may occur in AD patients, despite the absence of manifest cerebrovascular lesions. Therefore, TFPI may represent a candidate marker of endothelial damage in AD and might be used for the identification and monitoring of patients that would benefit from folate supplementation treatment. PMID- 20359778 TI - Functional correlates of instrumental activities of daily living in mild Alzheimer's disease. AB - Instrumental activities of daily living (IADL) includes the integration of task initiation, -planning, and -performance. Little is known on the cerebral perfusion correlates of these subcomponents of IADL in Alzheimer's disease (AD). In 121 AD patients, cerebral perfusion, using single-photon emission computed tomography, in 13 bilateral regions of interest (ROI) and the perfusion correlates of IADL subcomponents, rated on the Disability Assessment in Dementia scale, were explored. Significant correlations were observed between IADL initiation and multiple bilateral prefrontal-striatal-anterior cingulate ROI (p < 0.01), IADL planning and right occipital ROI (p < 0.05), and IADL performance and right parietal ROI (p < 0.05). Multiple regression, accounting for age, cognitive impairment, and depression severity, revealed significant relationship between right basal ganglia perfusion and IADL-initiation (R = 0.6, R(2) = 0.39, F(4,117) = 17.8, SE = 1.56; p < 0.001) and right occipital perfusion and IADL-planning (R = 0.6, R(2) = 0.34, F(4,117) = 19.5, SE = 1.47; p < 0.001). In AD, perfusion correlates of these subcomponents may be linked to the heterogenous cognitive processes involved in IADL. PMID- 20359780 TI - Effects of aging on the ventral and dorsal substantia nigra using diffusion tensor imaging. AB - Dopaminergic neurons in the substantia nigra produce dopamine for the nigrostriatal pathway that facilitates motor function. Postmortem examinations demonstrate an age-related loss of cells in the substantia nigra, with most of the cell loss focused on the dorsal substantia nigra compared with the ventral substantia nigra. The current study used diffusion tensor imaging (DTI) to provide the first in vivo assessment of age-related degeneration in specific segments of the substantia nigra of humans. Measures extracted from DTI of 16 young adults (19-27 years) and 15 older adults (55-71 years) showed that in the dorsal substantia nigra, fractional anisotropy was reduced and radial diffusivity was increased with age. In the ventral substantia nigra and red nucleus, there were no differences across age for the DTI measures. DTI provides a noninvasive technique that accurately reflects the established pattern of age-related cell loss in the dorsal and ventral substantia nigra, further suggesting the robust potential for using DTI to characterize degeneration in the nigrostriatal pathway in both health and disease. PMID- 20359779 TI - Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease. AB - Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimer's disease (AD). However, alterations in vascular function under in vivo conditions are poorly understood. In this study, we assessed cerebrovascular reactivity (CVR) in AD patients and age-matched controls using CO(2)-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared with controls, AD patients had widespread reduction in CVR in the rostral brain including prefrontal, anterior cingulate, and insular cortex (p < 0.01). The deficits could not be explained by cardiovascular risk factors. The spatial distribution of the CVR deficits differed drastically from the regions of cerebral blood flow (CBF) deficits, which were found in temporal and parietal cortices. Individuals with greater CVR deficit tended to have a greater volume of leukoaraiosis as seen on FLAIR MRI (p = 0.004). Our data suggest that early AD subjects have evidence of significant forebrain vascular contractility deficits. The localization, while differing from CBF findings, appears to be spatially similar to PIB amyloid imaging findings. PMID- 20359782 TI - [Project AP-21. Dream or reality?]. PMID- 20359781 TI - Atrophy and dysfunction of parahippocampal white matter in mild Alzheimer's disease. AB - In addition to atrophy of mesial temporal lobe structures critical for memory function, white matter projections to the hippocampus may be compromised in individuals with mild Alzheimer's disease (AD), thereby compounding the memory difficulty. In the present study, high-resolution structural imaging and diffusion tensor imaging techniques were used to examine microstructural alterations in the parahippocampal white matter (PWM) region that includes the perforant path. Results demonstrated white matter volume loss bilaterally in the PWM in patients with mild AD. In addition, the remaining white matter had significantly lower fractional anisotropy and higher mean diffusivity values. Both increased mean diffusivity and volume reduction in the PWM were associated with memory performance and ApoE epsilon4 allele status. These findings indicate that, in addition to partial disconnection of the hippocampus from incoming sensory information due to volume loss in PWM, microstructural alterations in remaining fibers may further degrade impulse transmission to the hippocampus and accentuate memory dysfunction. The results reported here also suggest that ApoE epsilon4 may exacerbate PWM changes. PMID- 20359783 TI - [Regulation of smoking reduces the prevalence of smokers and tobacco consumption]. PMID- 20359784 TI - [High blood pressure: beyond the guidelines]. PMID- 20359785 TI - [Impact on the population of media campaigns on the influenza H1N1A pandemic. Incidence on the act of shaking hands on saying goodbye, in a rural health centre. Changes in social behavior due to the risk of contracting influenza H1N1A]. PMID- 20359786 TI - [Occupational passive smoker. When will there be a new anti-smoking law?]. PMID- 20359787 TI - Hairpin-shaped tetranuclear palladium(II) complex: synthesis, crystal structure, DNA binding and cytotoxicity activity studies. AB - A novel tetranuclear palladium(II) complex [Pd(4)(phen)(4) (micro pydc)(4)].10H(2)O (phen = 1,10-phenanthroline, pydc = pyridine-3,4-dicarboxylate) has been synthesized and characterized. In the tetranuclear complex, two pairs of dipalladated [Pd(phen)] moieties are bridged together by four pydc, presenting a hairpin molecular shape. The binding of the title complex with fish sperm DNA (FS DNA) has been investigated by UV spectrum and fluorescence spectrum. All the results indicate that the complex bind to DNA in an intercalative mode and considerating the molecular shape and size, the dipalladated phenanthroline moieties bisintercalate to the base pairs of DNA. Agarose gel electrophoresis assay demonstrates the ability of the complex to cleave the pBR322 plasmid DNA. Cytotoxic activity studies show the complex exhibited good cytotoxic activity against four different cancer cell lines. PMID- 20359788 TI - Synthesis and structure-activity relationship study of 8-hydroxyquinoline-derived Mannich bases as anticancer agents. AB - To continue our early study on the structural modifications of clioquinol, more 8 hydroxyquinoline-derived Mannich bases were synthesized and examined for growth inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8 hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study. PMID- 20359789 TI - Design, synthesis and antiproliferative activity of styryl lactones related to (+)-goniofufurone. AB - This paper describes a straightforward divergent synthesis of (+)-goniofufurone mimics (4, 5 and 6) starting from d-xylose. In a preliminary bioassay, analogues 4 and 5 exhibited a submicromolar antiproliferative activity towards HL-60 cells, while the corresponding parent compound 1 was completely inactive against this cell line. At the same time, these molecules showed approximately 10-fold stronger cytotoxicity in the same cell line when compared to the standard anticancer drug doxorubicin (DOX). Analogue 6 displayed 18- and 3-fold higher potency in Raji cell line when compared to control compounds 1 and DOX, respectively. A new divergent route for the preparation of (+)-goniofufurone (1) and (+)-crassalactone C (3) from d-xylose is also disclosed. PMID- 20359790 TI - [Retroperitoneal fibrosis and multiple myeloma: fortuitous association?]. AB - We report a 59-year-old man presenting with retroperitoneal fibrosis (RF) associated with IgG lambda multiple myeloma. Recent clinical and immunohistochemical findings suggest that RF might be a particular expression of plasma cell/lymphoid dyscrasia, and that this association is not merely fortuitous. We review the pathophysiological evidence supporting this hypothesis. PMID- 20359791 TI - [Celiac disease]. AB - Celiac disease is an enteropathy due to gluten intake in genetically predisposed individuals (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Clinical features observed in celiac disease are extremely various and anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may be the only presenting manifestations. Diagnosis relies on the evidence of histological villous atrophy in proximal small bowel and the presence of specific serum antibodies. Treatment relies on eviction of gluten (wheat, barley, rye) from diet. Gluten free diet allows prevention of malignant complications such as small bowel adenocarcinoma and lymphoma, and osteopenia. The main cause of resistance to gluten free diet is its poor observance. If not the case, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T-cell lymphoma should be suspected. Current therapeutic challenges concern alternative to gluten free diet and new efficient treatments of lymphomatous complications. PMID- 20359792 TI - The relationship between BMI and percent body fat, measured by bioelectrical impedance, in a large adult sample is curvilinear and influenced by age and sex. AB - OBJECTIVE: The study aimed to establish the effects of age, gender and age-gender interactions on BMI-% fat relationships over a wide range of BMI and age. It also aimed to examine controversies regarding linear or curvilinear BMI-% fat relationships. METHODS: Body composition was measured using validated bio impedance equipment (Bodystat) in a large self-selected sample of 23,627 UK adults aged 18-99 (99% <=70) years, of which 11,582 were males with a mean BMI of 26.3+/-4.7 (sd) kg/m(2), and 12,044 females, with a mean BMI of 25.7+/-5.1 kg/m(2). Multiple regression analysis was used. RESULTS: BMI progressively increased with age in women and plateaued between 40 and 70 years in men. At a fixed BMI, body fat mass increased with age (1.9 kg/decade), as did % fat (1.1 1.4% per decade). The relationship between BMI and % fat was found to be curvilinear (quadratic) rather than linear, with a weaker association at lower BMI. There was also a small but significant age-gender interaction. CONCLUSION: The association between BMI and % body fat is not strong, particularly in the desirable BMI range, is curvilinear rather than linear, and is affected by age. PMID- 20359793 TI - Biosorption of uranium (VI) by immobilized Aspergillus fumigatus beads. AB - Biosorption of uranium (VI) ions by immobilized Aspergillus fumigatus beads was investigated in a batch system. The influences of solution pH, biosorbent dose, U (VI) concentration, and contact time on U (VI) biosorption were studied. The results indicated that the adsorption capacity was strongly affected by the solution pH, the biosorbent dose and initial U (VI) concentration. Optimum biosorption was observed at pH 5.0, biosrobent dose (w/v) 2.5%, initial U (VI) concentration 60 mg L(-1). Biosorption equilibrium was established in 120 min. The adsorption process conformed to the Freunlich and Temkin isothermal adsorption models. The dynamic adsorption model conformed to pseudo-second order model. PMID- 20359794 TI - Atmospheric radon in Hong Kong. AB - For the first time in Hong Kong, atmospheric radon concentration was continuously monitored between November 2007 and October 2008. This paper presents the results obtained during the 12-month period. The annual mean atmospheric radon concentration in Hong Kong was found to be 9.3 Bqm(-3) which was close to the level at neighbouring places like Guangdong and Taiwan. An estimation of the dose arising from atmospheric radon to the Hong Kong population was made. The meteorological effects on the variation of atmospheric radon concentration were discussed. It was found that the origin of the airmass and stability of the local atmosphere played vital roles in the seasonal and diurnal variations respectively, whereas precipitation caused abrupt changes in rainy days. An attempt was also made to find out the contribution of atmospheric radon to the ambient gamma dose rate. PMID- 20359795 TI - Redox chemistry of sulphate and uranium in a phosphogypsum tailings dump. AB - The present study aims to assess the effect of redox conditions existing within the tailings dump on the stability of phosphogypsum (e.g. sulphate reduction) and uranium(VI). Phosphogypsum sampling and in-situ measurements were carried out at a coastal tailings dump in Vasiliko Cyprus, pH, E(H) and solubility experiments were performed in simulated laboratory systems and thermodynamic calculations using MINTEQA2. Generally, in the open tailings dump oxidizing conditions predominate stabilizing sulphur and uranium in their hexavalent oxidation states. On the other hand, after the application of a soil/vegetative cover and in the presence of natural organic matter, anoxic conditions prevail (E(H) < -70 mV) resulting in S(VI) and U(VI) reduction to S(-II) and U(IV), respectively. Although, the sulphide anion can form very insoluble compounds with heavy metal ions (e.g. Cd(II), Pb(II) etc.) and U(IV) oxide has very low solubility, partial reduction of sulphate to sulphide within gypsum may affect the stability of phosphogypsum resulting in enhanced erosion of the material by rain- and seawater and washing out of contaminants in particulate/colloidal form. PMID- 20359796 TI - Psychometric properties and factor structure of the Fertility Problem Inventory in a sample of infertile women undergoing fertility treatment. AB - OBJECTIVE: to examine the psychometric properties of the Fertility Problem Inventory (FPI) originally developed by Newton et al. (1999); as there are no data concerning the factorial structure of the FPI, a special focus is placed on construct validity through factor analysis. SETTING: public hospital in Athens, Greece. DESIGN: a cross-sectional study. PARTICIPANTS: 108 women undergoing fertility treatment with in-vitro fertilisation. METHODS: the FPI was 'forward backward' translated from English to Greek. The translated instrument was then administered to a set of infertile women for pilot testing. Principal axis factoring with promax rotation was used to test the factor structure of the FPI. Measures of anxiety State Trait Anxiety Inventory, depression (Center for Epidemiologic Studies--Depression Scale) and mood states Profile of Mood States were used to assess the convergent validity of the FPI. Cronbach's alpha was used to measure internal consistency of the FPI scales. FINDINGS: exploratory factor analysis suggested four factors. The majority of relationship and sexual concern items grouped into one solid factor, named 'spousal concern'. The original scales of social concern, need for parenthood and rejection of childfree lifestyle were reproduced after rearranging nine cross-loading items. Construct validity was confirmed by computing correlations between the derived FPI scales and conceptually similar constructions of anxiety, depression and mood states. Internal consistency reliability was satisfactory. CONCLUSION: the FPI was found to have a relatively stable factor structure and satisfactory reliability, and convergent and discriminant validity. The FPI may enable researchers and clinicians to apply a reliable measure that focuses on various/many dimensions of infertility-related stress. PMID- 20359797 TI - The middle layer of lumbar fascia can transmit tensile forces capable of fracturing the lumbar transverse processes: an experimental study. AB - BACKGROUND: Transversus abdominis and its aponeurotic attachment to the lumbar transverse processes via the middle layer of lumbar fascia are of proposed clinical and biomechanical importance. Moderate traction on these structures (simulating submaximal contraction of transversus abdominis) is reported to influence segmental motion, but their tensile capacity is unknown and the effects of sudden, maximal traction on these attachments and the transverse processes are uncertain. METHODS: In 15 embalmed cadaver abdomens, the middle layer of lumbar fascia was isolated, gripped and rapid tension applied in either a lateral or posteroanterior direction (simulating forces that may produce avulsion and traumatic fractures). Peak forces prior to tissue failure were recorded and the gross effects of traction documented. FINDINGS: Lumbar transverse process fractures were produced in all specimens; by transverse traction in 50% of tests and posteroanterior force in 80%. In the remainder the middle layer of lumbar fascia was torn. Mean transverse and posteroanterior peak forces reached in the middle layer of lumbar fascia prior to failure were 82 N (range 20-190 N) and 47 N (range 25-70 N), respectively. INTERPRETATION: The middle layer of lumbar fascia can transmit substantial tensile forces to lumbar vertebrae, capable of transverse process fracture under experimental conditions. Tensile capacity is likely to be even greater in-vivo. This suggests transversus abdominis and the middle layer of lumbar fascia can strongly influence vertebral motion, should be incorporated in biomechanical models of the spine and considered as potential contributors to transverse process fractures by avulsion. PMID- 20359798 TI - A comparison of the thermal properties of 2- and 3-fluted drills and the effects on bone cell viability and screw pull-out strength in an ovine model. AB - BACKGROUND: Drilling of bone is associated with an increase in temperature of the surrounding bone which may result in osteonecrosis. METHODS: In this study, cutting efficiency and thermal properties of one 2-fluted drill and two 3-fluted drills were determined in vitro using a porcine model. Drills were then used to create pilot holes in an in vivo ovine model to facilitate implantation of pedicle screws. The effect of the characteristic thermal profiles of each drill on cortical bone cell viability and screw pull-out strength was then assessed. FINDINGS: Cutting efficiencies of both 3-fluted designs were found to be greater than that of the 2-fluted drill, but this did not translate into a decrease in the maximum temperatures during drilling for both drills. Histologically, no empty osteocyte lacunae were seen at 2 or 4 weeks, suggesting that temperatures were not sufficiently high enough to induce thermonecrosis in the ovine tibia. No differences were found in the pull-out strength of the screws. INTERPRETATION: Both 2- and 3-fluted drills are currently in clinical use. Despite the theoretical advantage that 3-fluted drills possess over their 2-fluted counterparts, there is a lack of evidence in the literature in support of their use. In this study the observed increases in cutting efficiency of the 3-fluted drills tested did not translate into a reduction in heat generation or improvement in bone healing or screw fixation. PMID- 20359799 TI - Lower limb muscle pre-motor time measures during a choice reaction task associate with knee abduction loads during dynamic single leg landings. AB - BACKGROUND: Female neuromuscular control during dynamic landings is considered central to their increased ACL injury risk relative to males. There is limited insight, however, into the neuromuscular parameters governing this risk, which may hinder prevention success. This study targeted a new screenable and potentially trainable neuromuscular risk factor. Specifically, we examined whether lower limb muscle pre-motor times, being the time between stimulus presentation and initiation of the muscle EMG burst, elicited during a simple choice reaction task correlated with knee abduction loads during separate single leg landings. METHODS: Twenty female NCAA athletes had muscle (n=8) pre-motor time and knee biomechanics data recorded bilaterally during a choice reaction task. Knee biomechanics were also quantified during anticipated and unanticipated single (dominant and non-dominant) leg landings. Mean peak knee abduction loads during landings were submitted to a two-way ANOVA to test for limb and decision effects. Individual regression coefficients were initially computed between-limb based muscle pre-motor times and peak abduction moments elicited during both the choice reaction and landing tasks. Limb-based linear stepwise regression coefficients were also computed between muscle PMT's demonstrating significant (P<0.05) individual associations and peak knee abduction moments during landings. FINDINGS: Peak knee abduction moments were significantly (P=0.0001) larger during unanticipated (51.25 (7.41) Nm) compared to anticipated (38.93 (9.32) Nm) landings. Peak abduction moments were significantly (P<0.05) correlated with bilateral medial gastrocnemius (r=0.62 dominant; r=0.63 non-dominant) and medial hamstring (r=0.77 dominant; r=0.79 non-dominant) pre-motor times elicited within the choice reaction task. Peak abduction moments during anticipated landings were significantly (P<0.05) correlated with both dominant (r=0.60) and non-dominant (r=0.59) medial hamstring pre-motor times. For unanticipated landings, non dominant and dominant peak knee abduction moments were significantly correlated with medial hamstring pre-motor time (r=0.78) and combined medial gastroc and medial hamstring pre-motor times (r=0.94) respectively. INTERPRETATION: Medial muscle pre-motor times during a specific choice reaction task are associated with peak knee abduction loads during separate single leg landings. These muscles appear critical in stabilizing the knee against the extreme dynamic load states associated with such tasks. Targeted screening and training of supraspinal processes governing these muscle pre-motor times may ultimately enable external knee loads associated with landings to be more effectively countered by the overarching neuromuscular strategy. PMID- 20359800 TI - Females exhibit shorter paraspinal reflex latencies than males in response to sudden trunk flexion perturbations. AB - BACKGROUND: Females have a higher risk of experiencing low back pain or injury than males. One possible reason for this might be altered reflexes since longer paraspinal reflex latencies exist in injured patients versus healthy controls. Gender differences have been reported in paraspinal reflex latency, yet findings are inconsistent. The goal here was to investigate gender differences in paraspinal reflex latency, avoiding and accounting for potentially gender confounding experimental factors. METHODS: Ten males and ten females underwent repeated trunk flexion perturbations. Paraspinal muscle activity and trunk kinematics were recorded to calculate reflex latency and maximum trunk flexion velocity. Two-way mixed model analyses of variance were used to determine the effects of gender on reflex latency and maximum trunk flexion velocity. FINDINGS: Reflex latency was 18.7% shorter in females than in males (P=0.02) when exposed to identical trunk perturbations, and did not vary by impulse (P=0.38). However, maximum trunk flexion velocity was 35.3% faster in females than males (P=0.01) when exposed to identical trunk perturbations, and increased with impulse (P<0.01). While controlling for differences in maximum trunk flexion velocity, reflex latency was 16.4% shorter in females than males (P=0.04). INTERPRETATION: The higher prevalence of low back pain and injury among females does not appear to result from slower paraspinal reflexes. PMID- 20359802 TI - A rapid bioassay for detecting saxitoxins using a Daphnia acute toxicity test. AB - Bioassays using Daphnia pulex and Moina micrura were designed to detect cyanobacterial neurotoxins in raw water samples. Phytoplankton and cyanotoxins from seston were analyzed during 15 months in a eutrophic reservoir. Effective time to immobilize 50% of the exposed individuals (ET50) was adopted as the endpoint. Paralysis of swimming movements was observed between approximately 0.5 3 h of exposure to lake water containing toxic cyanobacteria, followed by an almost complete recovery of the swimming activity within 24 h after being placed in control water. The same effects were observed in bioassays with a saxitoxin producer strain of Cylindrospermopsis raciborskii isolated from the reservoir. Regression analysis showed significant relationships between ET50 vs. cell density, biomass and saxitoxins content, suggesting that the paralysis of Daphnia in lake water samples was caused by saxitoxins found in C. raciborskii. Daphnia bioassay was found to be a sensitive method for detecting fast-acting neurotoxins in natural samples, with important advantages over mouse bioassays. PMID- 20359801 TI - How best to use new therapies in multiple myeloma. AB - Advances in the molecular understanding of myeloma have led to the development of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib). When used alone, these agents have significant activity against myeloma and responses increase significantly when they are combined with additional agents including glucocorticosteroids and chemotherapeutic agents such as alkylators. There is a drive to use these novel agents in patients with newly diagnosed myeloma, where they lead to impressive response rates with increasing duration of responses. In addition, novel agents are now the mainstays of therapy for relapsed disease. In the following paper, we summarize the key observations from recent completed and ongoing studies that determined the effect of these novel therapies both in the setting of newly diagnosed myeloma and for relapsed disease. We also discuss our approach to the use of these agents in specific myeloma settings. PMID- 20359803 TI - Factors influencing gender differences in smoking and their separate contributions: evidence from South Korea. AB - This paper explores gender differences in smoking using information on 15,277 adults obtained from the Korea National Health and Nutrition Examination Surveys of 2001 and 2005. Applying a decomposition approach extended from the Oaxaca Blinder method, we obtained factors influencing gender differences in smoking and estimated their separate contributions. According to the outcomes of decomposition analyses, gender differences in smoking-tendency (or inclination to smoke) accounted for 98% of the total gender difference in smoking. When the gender difference in smoking was decomposed into specified factors, the difference in smoking-tendency between married men and women was found to be the most crucial factor as it explained 11% of the total gender difference in smoking. The gender difference in the proportion of persons attaining a low level of education contributed to a 6% reduction of the total gender difference in smoking. Additionally, factors influencing the gender-specific smoking-tendency were found to be important in explaining the gender difference in smoking. We conclude that, understanding separate contributions of sets of factors affecting gender differences in smoking and devising appropriate policies could effectively reduce the smoking rate of a target gender group to the level of that of a reference gender group. PMID- 20359804 TI - Recipes for medical education reform: will different ingredients create better doctors? A commentary on Sales and Schlaff. PMID- 20359805 TI - Context, evidence and attitude: the case for photography in medical examinations of asylum seekers in the Netherlands. AB - Can photographs of scars serve as evidence of torture? Amnesty International's Medical Examination Group in the Netherlands (AI-MEG) has, for more than a decade, been photographing torture scars to supplement the testimonies of asylum seekers who have been denied refuge. AI-MEG only intervenes at this point, when asylum seekers face extradition. Proving allegations of torture is of vital importance, as asylum seekers face rising anti-immigrant sentiment in European countries. All victims examined by AI-MEG present a combination of mental, physical and emotional scars. We summarize five cases where AI-MEG used photography in their medical examinations, and consider the ethical role physicians play in helping asylum seekers obtain refuge. Though photographs cannot capture all forms of trauma, as visual documents, they are a compelling form of concrete evidence of torture. In this way, photographs complement verbal testimonies and help doctors and immigration authorities to see and understand physical scars left by various forms of torture. AI-MEG explains in medical terms the connections between the visible late sequelae of torture and victims' testimonies. They then assess whether or not the physical scars are consistent with the forms of torture recounted by victims, using the terminology of the Istanbul Protocol (1999), the United Nations-adopted manual of guidelines that explains how to document torture. This paper outlines the medical examination process and argues for the use of photography as medical evidence on behalf of asylum seekers. PMID- 20359806 TI - Reforming medical education: a review and synthesis of five critiques of medical practice. AB - For physicians to provide appropriate healthcare at a reasonable cost, health reform may not be enough. This essay discusses the scope of educational reform needed in the U.S. to train tomorrow's physicians to practice effectively in an increasingly complicated health care arena. We undertook a review and synthesis of five critiques of medical practice in the U.S.: of quality, evidence-based medicine, population medicine, health policy and heuristics. Our findings suggest that physicians are inadequately trained to function in the complex organizational and social systems that characterize modern practice. Successful health care reform in the U.S. will require physicians who are trained not only in bio-medicine, but also in the social sciences. Other developed countries, which have both greater government control of health care and a culture less oriented to individualism, may have less need for specific efforts to train physicians in the social sciences but could still benefit from considering an expanded curriculum. Effective educational reform must address the medical admissions process, academic and intellectual preparation, and professional and clinical training. PMID- 20359807 TI - Socio-economic status and oral health-related behaviours in Korean adolescents. AB - The principle objective of this study was to assess the association between socio economic status (SES) and oral health-related behaviours in Korean adolescents aged 13-18, using the Family Affluence Scale (FAS). The secondary objective was to assess the influences of other factors (pocket money, school type, family structure and psychological factors) on this association. Cross-sectional data were from the national 2007 Korean Youth Risk Behavior Web-based Survey. Oral health-related behaviours included health-enhancing behaviours (frequency of toothbrushing and dental visits) and health-compromising behaviours (smoking and frequency of intake of soft drinks and confections). Logistic regression models were used to analyse the data. To assess the influence of other factors, additional models adjusting for sex, school grade and each of the other factors were compared to the initial model, which adjusted for sex and school grade only. We found that family affluence had a linear association with health-enhancing behaviours and a roughly U-shaped association with health-compromising behaviours. After adjusting for a number of variables, the linear association with health-enhancing behaviours persisted. The U-shaped association with health compromising behaviours remained but was partly attenuated and flattened. In addition, we found a marked influence of school type and family structure and pocket money on the association between FAS and oral health-compromising behaviours. The findings indicate that the health-enhancing behaviours of adolescents were strongly associated with family affluence, but the health compromising behaviours were more strongly linked to factors other than family affluence. However, it is difficult to determine which factors contribute most in relation to family affluence because of other confounding factors, such as the education system, peer group, youth culture, part-time work and advertising. Therefore, further studies are needed to assess factors that interact with family SES to better understand the association between the SES and the oral health compromising behaviours of adolescents. PMID- 20359808 TI - Male reproductive control of women who have experienced intimate partner violence in the United States. AB - Women who have experienced intimate partner violence (IPV) are consistently found to have poor sexual and reproductive health when compared to non-abused women, but the mechanisms through which such associations occur are inadequately defined. Through face-to-face, semi-structured in-depth interviews, we gathered full reproductive histories of 71 women aged 18-49 with a history of IPV recruited from a family planning clinic, an abortion clinic and a domestic violence shelter in the United States. A phenomenon which emerged among 53 respondents (74%) was male reproductive control which encompasses pregnancy promoting behaviors as well as control and abuse during pregnancy in an attempt to influence the pregnancy outcome. Pregnancy promotion involves male partner attempts to impregnate a woman including verbal threats about getting her pregnant, unprotected forced sex, and contraceptive sabotage. Once pregnant, male partners resort to behaviors that threaten a woman if she does not do what he desires with the pregnancy. Reproductive control was present in violent as well as non-violent relationships. By assessing for male reproductive control among women seeking reproductive health services, including antenatal care, health care providers may be able to provide education, care, and counseling to help women protect their reproductive health and physical safety. PMID- 20359809 TI - Poverty, vulnerability, and provision of healthcare in Afghanistan. AB - This paper presents findings on conditions of healthcare delivery in Afghanistan. There is an ongoing debate about barriers to healthcare in low-income as well as fragile states. In 2002, the Government of Afghanistan established a Basic Package of Health Services (BPHS), contracting primary healthcare delivery to non state providers. The priority was to give access to the most vulnerable groups: women, children, disabled persons, and the poorest households. In 2005, we conducted a nationwide survey, and using a logistic regression model, investigated provider choice. We also measured associations between perceived availability and usefulness of healthcare providers. Our results indicate that the implementation of the package has partially reached its goal: to target the most vulnerable. The pattern of use of healthcare provider suggests that disabled people, female-headed households, and poorest households visited health centres more often (during the year preceding the survey interview). But these vulnerable groups faced more difficulties while using health centres, hospitals as well as private providers and their out-of-pocket expenditure was higher than other groups. In the model of provider choice, time to travel reduces the likelihood for all Afghans of choosing health centres and hospitals. We situate these findings in the larger context of current debates regarding healthcare delivery for vulnerable populations in fragile state environments. The 'scaling-up process' is faced with several issues that jeopardize the objective of equitable access: cost of care, coverage of remote areas, and competition from profit orientated providers. To overcome these structural barriers, we suggest reinforcing processes of transparency, accountability and participation. PMID- 20359810 TI - Could a mediolateral episiotomy prevent obstetric anal sphincter injury? AB - OBJECTIVE: To analyse the significance of risk factors and the role of episiotomy in preventing obstetric anal sphincter injury at vaginal delivery. STUDY DESIGN: This is a retrospective cross-sectional study in the Norfolk and Norwich University Hospital in the UK. All caesarean sections and non-vertex presentations were excluded, which resulted in a study population of 10,314 deliveries. Obstetric anal sphincter injury (OASI) was defined as third or fourth degree tears to the anal sphincter muscles, with or without a tear involving the anal mucosa. First a univariate analysis was done to identify factors that had a significant association with OASI. Factors included parity, age, gestation, labour induction method, duration of second stage, use of epidural analgesia, episiotomy, method of delivery, time and month of delivery, and birth weight. All factors were then combined in a multivariate logistic regression analysis. The multivariate analysis was then repeated including only factors that had a significant association with OASI in the univariate analysis. Adjusted odds ratios with 95% confidence intervals (CI) were calculated. RESULTS: The frequency of anal sphincter lacerations was 3.2%. There were statistically significant associations between an increased incidence of OASI and parity, birth weight, method of delivery and shoulder dystocia. Women giving birth without a mediolateral episiotomy were 1.4 times more likely to experience OASI (95% CI 1.021-1.983). Interestingly, the incidence of OASI has risen between 2005 and 2007. CONCLUSION: Parity, age, birth weight, method of delivery and shoulder dystocia are strongly associated with obstetric anal sphincter injury. Mediolateral episiotomy appears to be protective against OASI but a randomised controlled trial would be needed to confirm this. The rising incidence of OASI after normal vaginal deliveries may be related to adoption of the hands off technique or increased identification of tears. PMID- 20359811 TI - A comparative study on the properties, mechanisms and process designs for the adsorption of non-ionic or anionic dyes onto cationic-polymer/bentonite. AB - The adsorption properties and mechanisms of a cationic-polymer/bentonite complex (EPI-DMA/bentonite), prepared from polyepicholorohydrin-dimethylamine and bentonite, for non-ionic dyes (Disperse Blue SBL and Vat Scarlet R) and anionic dyes (Reactive Violet K-3R and Acid Dark Blue 2G) were investigated in this study. The solution pH, presence of salt and surfactant can significantly affect the dye removal efficiency. The equilibrium data were analyzed using the Langmuir and Freundlich models. The Langmuir model is the most suitable to describe non ionic dye adsorption, but for anionic dyes the Freundlich model is best. The kinetic data for the adsorption of different dyes were analyzed using pseudo first- and second-order equations, and the experimental data conformed to the pseudo second-order kinetic model better. The possibility of intraparticle diffusion was also examined by using the intraparticle diffusion equation. The single-stage batch adsorber design for the adsorption of both types of dyes onto EPI-DMA/bentonite was studied based on the Langmuir isotherm model for non-ionic dyes and the Freundlich isotherm model for anionic dyes. The results showed that the required amount of EPI-DMA/bentonite for 95% dye removal in 5 L dye solution with a concentration of 50 mg/L is 378.0 g for DB SBL, 126.5 g for VS R, 9.7 g for RV K-3R and 15.5 g for ADB 2G. PMID- 20359812 TI - Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy. AB - CONTEXT: The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required. OBJECTIVE: To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC. EVIDENCE ACQUISITION: Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles. EVIDENCE SYNTHESIS: Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2. CONCLUSIONS: CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC. PMID- 20359813 TI - Matrix metalloproteinase-9 is required for tubular network formation and migration of resistant breast cancer cells MCF-7 through PKC and ERK1/2 signalling pathways. AB - Matrix metalloproteinase-9 (MMP-9) strongly influences tumor development and metastasis. Using resistant (rMCF-7) and sensitive (sMCF-7) breast cancer lines we investigated the role of MMP-9 in cell migration (CM) and tubular network (TN) formation, two processes implied in tumor growth and metastasis. Our data demonstrate that MMP-9 which is critical for CM is necessary but not sufficient for TN formation and suggest a link between MDR1/P-gp and constitutive MMP-9. Both TN formation and CM are dependent on PKC and ERK1/2 pathways. This study reinforces the logic of combining therefore MMP inhibitors in cancer therapy, especially in patients with chemoresistance and invasion/metastasis. PMID- 20359814 TI - Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to cirsimaritin-induced apoptosis in human gallbladder carcinoma GBC-SD cells. AB - In this study, the anticancer effect of cirsimaritin, a natural flavonoid, against human gallbladder carcinoma cell line GBC-SD and the underlying mechanisms were investigated. Cirsimaritin inhibited the growth of tumor cells and induced mitochondrial apoptosis in GBC-SD cells. In addition, cirsimaritin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt, while knock-down of CHOP dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of cirsimaritin. Furthermore, cirsimaritin provoked the generation of reactive oxygen species in GBC-SD cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting cirsimaritin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in GBC-SD cells. PMID- 20359815 TI - Performance of mesophilic anaerobic granules for removal of octahydro-1,3,5,7 tetranitro-1,3,5,7-tetrazocine (HMX) from aqueous solution. AB - The performance of mesophilic anaerobic granules to degrade octahydro-1,3,5,7 tetranitro-1,3,5,7-tetrazocine (HMX) was investigated under various conditions. The results of batch experiments showed that anaerobic granules were capable of removing HMX from aqueous solution with high efficiency. Both biotic and abiotic mechanisms contributed to the removal of HMX by anaerobic granules under mesophilic conditions. Adsorption appeared to play a significant role in the abiotic process. Furthermore, HMX could be biodegraded by anaerobic granules as the sole substrate. After 16 days of incubation, 99.04% and 96.42% of total HMX could be removed by 1g VSS/L acclimated and unacclimated granules, respectively. Vancomycin, an inhibitor of acetogenic bacteria, caused a significant inhibition of HMX biotransformation, while 2-bromoethanesulfonic acid, an inhibitor of methanogenic bacteria, only resulted in a slight decrease of metabolic activity. The presence of the glucose, as a suitable electron donor and carbon source, was found to enhance the degradation of HMX by anaerobic granules. Our study showed that sulfate had little adverse effects on biotransformation of HMX by anaerobic granules. However, nitrate had significant inhibitory effect on the extent of HMX removal especially in the initial period. This study offered good prospects of using high-rate anaerobic technology in the treatment of munition wastewater. PMID- 20359816 TI - Chemical changes during vermicomposting of sago industry solid wastes. AB - A laboratory study was undertaken to examine the temporal changes in physico chemical properties during vermicomposting of sago industry waste. The sago industry waste was blended with cow dung, poultry manure at various proportions, kept for pre-treatment for 21 days and subsequently vermicomposted for a period of 45 days under shade. Earthworm species (Eisenia foetida) was introduced at the rate of 50 g/kg of waste. The substrate moisture content and temperature were monitored regularly. The vermicomposts were sampled at 0, 15, 30 and 45 days for the assessment of temporal changes in physico-chemical properties. The data revealed vermicomposting of sago wastes, cow dung and poultry manure mixed at equal proportion (1:1:1) produced a superior quality manure with desirable C:N ratio and higher nutritional status than composting. E. foetida is an earthworm suitable for composting organic wastes such as poultry manure with extreme pH and high temperature and sago waste with high organic carbon in a shorter period of time. This study suggests that the sago industry solid waste could be effectively converted into highly valuable manure that can be exploited to promote crop production. PMID- 20359817 TI - Electrokinetic remediation of PAH mixtures from kaolin. AB - Because of increased industrialisation and new manufacturing processes, elevated amounts of organic pollutants are released into the environment. Hydrophobic organic contaminants, including polycyclic aromatic hydrocarbons (PAHs), are toxic and persistent contaminants that are not treatable by natural attenuation. In this work, electroremediation is proposed for cleaning soil contaminated by organic compounds. Model samples of kaolin clay polluted with a mixture of PAHs (fluoranthene, pyrene, and benzanthracene) were treated. Electroremediation of kaolin contaminated with a mixture of these three PAHs was carried out using a solution of 1% Tween 80 and 0.1 M Na(2)SO(4) as the processing fluid. Under these conditions, low removal was obtained. However, by using the same processing fluid and controlling the pH at 7 in the anode chamber, high electro-osmotic flow was detected. After the treatment, removal of around 40% of the PAHs was achieved. The created environment inside the soil during the electrokinetic treatment greatly influenced the process. The results of this work reveal the high potential for the application of the electroremediation process on soil polluted with different PAHs. PMID- 20359818 TI - Effects of TiO2 coating dosage and operational parameters on a TiO2/Ag photocatalysis system for decolorizing Procion red MX-5B. AB - In this study, titanium dioxide (TiO(2)) powder was coated onto the surface of a dendritic silver (Ag) carrier to synthesize TiO(2)/Ag for decolorizing Procion red MX-5B (MX-5B), and related operation factors were also studied. The results showed that even without ultraviolet-A (UVA) irradiation, the Ag carrier from the TiO(2)/Ag catalyst had oxidizing ability, which could effectively degrade MX-5B color, but TiO(2) was ineffective. In addition, TiO(2) from TiO(2)/Ag demonstrated photocatalysis performance when irradiated, and the Ag carrier further showed an electron-scavenging ability to mitigate electron-hole pair recombination, which can improve the photocatalytic efficacy. With the oxidization and electron-scavenging ability of Ag and the photocatalysis ability of TiO(2), TiO(2)/Ag can decolor MX-5B more efficiently than TiO(2). The heavier Ag carrier also improves the solid-liquid separation of nano-TiO(2), making TiO(2)/Ag more suitable for application in slurry systems of photocatalytic water treatment. When the TiO(2)/Ag coating ratio was 50% by weight, there was a sufficient amount of TiO(2) on Ag's surface with a good distribution, and it exhibited a good photocatalysis decolorizing effect. In a study of how operational factors impact the decolorizing of MX-5B in the TiO(2)/Ag photocatalysis system with UVA irradiation (UVA-TiO(2)/Ag), the decolorization efficiency was optimal when the solution was maintained at pH 6.35. The addition of 0.01 M hydrogen peroxide (H(2)O(2)) aided the photocatalysis decolorization efficiency, although excessive H(2)O(2) reacted with hydroxyl free radicals and decreased the active groups in the system, thereby reducing the photocatalysis activity. An operating temperature of 40 degrees C was conducive to MX-5B decolorization, which was better than operating at room temperature. PMID- 20359819 TI - Investigation on the activation of coal gangue by a new compound method. AB - In order to comprehensively utilize coal gangue as the main raw material in cementitious materials, improving its cementitious activity is a question of fundamental importance. In this paper, we present a new compound mechanical-hydro thermal activation (CMHTA) technology to investigate the activation effect of coal gangue, and the traditional mechanical-thermal activation (TMTA) technology was used as reference. The purpose of this study is to give a detailed comparison between these two methods with regard to the mineral composition, crystal structure and microstructure, by XRD, IR, MAS NMR, XPS and mechanical property analysis. The prepared coal gangue based blended cement, containing 52% of activated coal gangue C (by CMHTA technology), has a better mechanical property than activated coal gangue T (by TMTA technology) and raw coal gangue. The results show that both of the TMTA and CMHTA technologies can improve the cementitious activity of raw gangue greatly. Moreover, compared with TMTA, the mineral phases such as feldspar and muscovite in raw coal gangue were partially decomposed, and the crystallinity of quartz decreased, due to the effect of adding CaO and hydro-thermal process of CMHTA technology. PMID- 20359820 TI - Chemical stabilization of air pollution control residues from municipal solid waste incineration. AB - The by-products of the municipal solid waste incineration (MSWI) generally contain hazardous pollutants, with particular relevance to air pollution control (APC) residues. This waste may be harmful to health and detrimental to the environmental condition, mainly due to soluble salts, toxic heavy metals and trace organic compounds. Solidification/stabilization (S/S) with binders is a common industrial technology for treating such residues, involving however, a significant increase in the final mass that is landfilled. In our work, the chemical stabilization of APC residues by using NaHS x xH(2)O, H(3)PO(4), Na(2)CO(3), C(5)H(10)NNaS(2) x 3 H(2)O, Na(2)O x SiO(2) was investigated, and it was possible to conclude that all these additives lead to an improvement of the stabilization process of the most problematic heavy metals. Indeed, compliance leaching tests showed that after the stabilization treatment the waste becomes non-hazardous with respect to heavy metals. Chromium revealed to be a problematic metal, mainly when H(3)PO(4), Na(2)CO(3) and Na(2)O x SiO(2) were used for stabilization. Nevertheless, soluble phosphates are the most efficient additives for stabilizing the overall metals. The effect of the additives tested on the elements associated with soluble salts (K, Na, Cl(-)) is almost negligible, and therefore, the soluble fraction is hardly reduced without further treatment, such as pre-washing. PMID- 20359821 TI - Modeling the oxidation kinetics of Fenton's process on the degradation of humic acid. AB - The degradation of humic acid (HA) was carried out in the presence of the Fenton reagent. The experiments demonstrated that HA was removed by oxidation and coagulation. Moreover, the oxidation occurred mainly at the first 60 min and predominated the HA removal efficiency. A new kinetic model was established according to the generally accepted mechanism of high active OH oxidation in order to well describe the Fenton oxidation reaction in HA aqueous solution. The model embraced two key operating factors affecting the HA degradation in Fenton process, including the dosages of hydrogen peroxide and ferrous ion. The experimental data were fitted by using the most commonly used first- and the second-order reaction models and the new model, respectively. The goodness of fittings demonstrated that the new model could better fit the experimental data than the other two models, which indicated that this analytical model could better describe the kinetics of Fenton reaction mathematically and chemically. Results indicated that the oxidation rate and removal efficiency were strongly dependent on initial pH, initial concentration of Fenton reagents, initial HA concentration and reaction temperature. The experiments demonstrated that hydrogen peroxide and ferrous ion would approach their saturated value with increasing dosage. PMID- 20359822 TI - Experimental study on the fire protection properties of PVC sheath for old and new cables. AB - The objective of the present study is to analyze the fire protection properties of old and new cables through TG, FTIR and MCC experiments. The results show that the mass loss of old cable sheath is clearly larger than the new one when the temperature is higher than 550 K in air or nitrogen atmosphere. It suggests that the old cable sheath starts to pyrolyze generally at the same temperature based on the analysis of the onset temperatures of mass loss. The results also show that there is a main peak DTG for the old and new cable sheath under each condition. However, the main peak DTG of old cable sheath is larger than that of the new cable sheath, especially in air atmosphere. The FTIR experiments show that the HCl is released by the new cable later but more quickly than the old cable. The MCC experiments suggest that compared with the new one, the peak heat release rate is larger for the old cable. It illustrates that the old cable sheath generally pyrolyzes and combusts more strongly and completely than the new one. Namely, the fire protection properties of the old cable in old buildings are relatively weak. PMID- 20359824 TI - Naturalistic changes in insomnia symptoms and pain in temporomandibular joint disorder: a cross-lagged panel analysis. AB - An increasing number of prospective studies suggest a bi-directional association between the pain and sleep quality. Few of these investigations have controlled for synchronous correlations, an important source of extraneous variance in lagged associations, which may have confounded conclusions of prior investigations. Despite high rates of insomnia in temporomandibular joint disorders (TMD), no studies have examined temporal associations between naturalistic fluctuations in insomnia and pain in TMD. We conducted cross-lagged panel analysis to examine reciprocal temporal associations between 1-month changes in insomnia symptom severity and self-reported pain over 3 months among 53 TMD patients. This rigorous analytic strategy represents a comprehensive method to explore possible reciprocal temporal associations between insomnia and pain that controls for both auto- and synchronous correlations. Analyses revealed that initial-month increases in insomnia were associated with next-month increases in average daily pain, but not vice versa. The direction of the effect was such that initial-month increases in insomnia symptom severity were associated with next-month increases in average daily pain. These data suggest that naturally occurring fluctuations in insomnia symptom severity are prospectively associated with fluctuations in daily pain experience for persons with TMD. Potential mechanisms by which insomnia might influence pain in TMD and therapeutic implications of these findings are discussed. PMID- 20359825 TI - Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. AB - Extended viewing of movements of the intact hand in a mirror as well as motor imagery has been shown to decrease pain in phantom pain patients. We used functional magnetic resonance imaging to assess the neural correlates of mirrored, imagined and executed hand movements in 14 upper extremity amputees - 7 with phantom limb pain (PLP) and 7 without phantom limb pain (non-PLP) and 9 healthy controls (HC). Executed movement activated the contralateral sensorimotor area in all three groups but ipsilateral cortex was only activated in the non-PLP and HC group. Mirrored movements activated the sensorimotor cortex contralateral to the hand seen in the mirror in the non-PLP and the HC but not in the PLP. Imagined movement activated the supplementary motor area in all groups and the contralateral primary sensorimotor cortex in the non-PLP and HC but not in the PLP. Mirror- and movement-related activation in the bilateral sensorimotor cortex in the mirror movement condition and activation in the sensorimotor cortex ipsilateral to the moved hand in the executed movement condition were significantly negatively correlated with the magnitude of phantom limb pain in the amputee group. Further research must identify the causal mechanisms related to mirror treatment, imagined movements or movements of the other hand and associated changes in pain perception. PMID- 20359826 TI - Characterization of the electrical and optical properties of viologen devices using chlorophyll a as an electron excimer. AB - This paper uses self-assembled monolayers (SAMs) on an Au(111) substrate to detect the unique characteristics of viologen molecules using scanning tunneling microscopy (STM), and reports the orientation and surface changes of molecules at the nano level in real-time. In particular, the rectification characteristics of the viologen molecule were observed at the molecular level using scanning tunneling spectroscopy (STS). After verifying the rectification characteristics of viologen molecules, an experiment was carried out to demonstrate the possibility of applying viologen to photodiodes and switching devices by forming a thin film of chlorophyll a on the viologen SAMs using the Langmuir-Blodgett (LB) method. This material mimics the photoinduced electron transport phenomenon in the early stage of photosynthesis in living plants. This study demonstrates the applicability of viologen to bioelectronic photodiodes and switching devices based on photo effects by observing the topography, current sensing, and current voltage (I-V) characteristics using current-sensing atomic force microscopy (CS AFM) by introducing light to the AFM-tip/chlorophyll a/viologen/Au(111) substrate structure. PMID- 20359827 TI - Virulence of Mexican isolates of entomopathogenic fungi (Hypocreales: Clavicipitaceae) upon Rhipicephalus=Boophilus microplus (Acari: Ixodidae) larvae and the efficacy of conidia formulations to reduce larval tick density under field conditions. AB - The first objective was laboratory evaluation of the virulence of 53 Mexican isolates of fungi against larvae of Rhipicephalus (Boophilus) microplus. Thirty three isolates of Metarhizium anisopliae var. anisopliae (Metschnickoff) Sorokin (Hypocreales: Clavicipitaceae) and 20 isolates of Isaria (Paecilomyces) fumosorosea (fumosoroseus) (Wize) (Eurotiales: Trichomaceae) were tested on 7-day old larvae under laboratory conditions. Larvae were immersed in a suspension containing 10(8)conidia/mL and the CL(50) values were estimated. Then, field tests were conducted to determine the efficacy of formulations of the isolate with the highest virulence. M. anisopliae (Ma 14 isolate) was formulated with four carriers: Tween, Celite, wheat bran, and Citroline (mineral oil) and applied on pasture beds of Cynodon plectostachyus (L.), at a dose of 2 x 10(9)CFU/m(2). In the first trial, M. anisopliae was applied on plots naturally infested with larvae; in the second trial, tick populations in the experimental plots were eliminated and then re-infested with 20,000 7-day-old larvae. In the laboratory, all M. anisopliae isolates infected larvae with a mortality range between 2 and 100%; also, 13 of 20 I. fumosorosea isolates caused mortality rates between 7 and 94%. In the first field trial, 14 days post-application, conidial formulations in Celite and wheat bran caused 67.8 and 94.2% population reduction, respectively. In the second trial, the Tween formulation caused the highest larval reduction, reaching up to 61% (28 days post-application). Wheat bran formulation caused 58.3% larval reduction (21 days post-application) and was one of the most effective. The carriers and emulsifiers have a large impact on the effectiveness of conidial formulations. PMID- 20359828 TI - Severe burn injuries sustained whilst under inpatient psychiatric care--a worrying trend. PMID- 20359829 TI - Methods of "fake ID" obtainment and use in underage college students. AB - Fake IDs are highly prevalent among underage college students, and are strongly associated with heavy drinking. However it is not currently known how exactly fake IDs are most commonly obtained and used, and how often individuals are caught. Such information could aid law enforcement and school personnel in their enforcement responsibilities, and might further elucidate the extent and means by which students "make ethical compromises" to gain illegal access to alcohol. A cross-sectional online survey of 1098 underage students at a large Midwestern university indicated that comparable to previous findings, 21.0% reported possessing a fake ID (which was strongly associated with past-month frequent heavy drinking; OR=4.84, 95% CI=3.41-6.86). Of those with fake IDs, 93.5% reported having used them, and 29.1% reported having been caught. Greek (i.e., fraternity/sorority) members were more likely than others to obtain them through a Greek organization (OR=8.02, 95% CI=1.81-35.54). Also, men were more likely than women to buy (OR=2.74, 95% CI=1.57-4.77), yet less likely to be given them (OR=0.53, 95% CI=0.31-0.90). Future studies might examine whether and how fake ID capture reduces (or exacerbates) drinking over time. PMID- 20359830 TI - Positive family relationships and religious affiliation as mediators between negative environment and illicit drug symptoms in American Indian adolescents. AB - The present study tests how positive family relationships and religious affiliation mediate between negative familial and social environments, and adolescent illicit drug abuse/dependence symptoms. The theoretical framework is based on an integration of two theories: the ecological model of human development (Bronfenbrenner, 1979) and the social development model (Hawkins & Weis, 1985). We used a stratified random sample of 401 American Indian adolescents. A path analysis tested the integrative theoretical model. Findings showed that positive family relationships mediated the negative impact of addicted family members, violence victimization, and negative school environment on illicit drug abuse/dependence symptoms. Religious affiliation mediated the negative effect of deviant peers on positive family relationships. Intervention and prevention efforts may benefit from promoting positive family relationships and religious affiliation to reduce the impact of complex familial and social problems on illicit drug symptoms. PMID- 20359832 TI - Lobular neoplasia displaying central necrosis: a potential diagnostic pitfall. AB - The distinction between intraepithelial proliferations of ductal and lobular type is often straightforward. However, a small number of cases create diagnostic problems even for experienced pathologists. Among those is the recognized, but not always kept in mind, lobular neoplasia with "comedo-type" necrosis. Herein, we present six cases of lobular neoplasia with comedo necrosis. Three cases were classified correctly, whereas the three remaining cases were initially misdiagnosed as ductal carcinoma in situ with necrosis. Of these three misdiagnosed cases, one patient underwent radiation therapy before this study was carried out. The two other patients were correctly reclassified as lobular type in subsequent excisional biopsies. One case showed a focus of microinvasion. All six lesions were negative by E-cadherin immunohistochemistry. Our experience highlights that the correct differentiation between intraepithelial neoplasias of ductal and lobular type may be challenging, and that the correct differentiation is extremely important for prognostic information and therapeutic decisions. PMID- 20359831 TI - Family history of alcohol abuse associated with problematic drinking among college students. AB - Studies examining family history of alcohol abuse among college students are not only conflicting, but have suffered various limitations. The current report investigates family history of alcohol abuse (FH+) and its relationship with alcohol expectancies, consumption, and consequences. In the current study, 3753 student participants (35% FH+), completed online assessments. Compared to FH- same-sex peers, FH+ males and FH+ females endorsed greater overall positive expectancies, consumed more drinks per week, and experienced more alcohol-related negative consequences. Further, FH+ females evaluated the negative effects of alcohol to be substantially worse than FH- females. An ANCOVA, controlling for age, GPA, race, and alcohol expectancies, resulted in family history main effects on both drinking and consequences. An interaction also emerged between gender and family history, such that FH+ males were especially vulnerable to high levels of alcohol consumption. Results reveal the scope of FH+ individuals in the college environment and the increased risk for these students, particularly male FH+ students, suggesting a need for researchers and college health personnel to focus attention and resources on this issue. PMID- 20359833 TI - [Bleeding during the first trimester of pregnancy]. PMID- 20359834 TI - Detection and genotyping of Korean porcine rotaviruses. AB - Porcine group A rotavirus (GARV) is considered to be an important animal pathogen due to their economic impact in the swine industry and its potential to cause heterologous infections in humans. This study examined 475 fecal samples from 143 farms located in 6 provinces across South Korea. RT-PCR and nested PCR utilizing primer pairs specific for the GARV VP6 gene detected GARV-positive reactions in 182 (38.3%) diarrheic fecal samples. A total of 98 porcine GARV strains isolated from the GARV-positive feces were analyzed for G and P genotyping. Based on the sequence and phylogenetic analyses, the most predominant combination of G and P genotypes was G5P[7], found in 63 GARV strains (64.3%). The other combinations of G and P genotypes were G8P[7] (16 strains [16.3%]), G9P[7] (7 strains [7.1%]), G9P[23] (2 strains [2.0%]), and G8P[1] (1 strain [1.0%]). The counterparts of G or P genotypes were not determined in three G5, five P[7], and one P[1] strains. Interestingly, phylogenetic analysis indicated that all Korean G9 strains were more closely related to lineage VI porcine and human viruses than to other lineages (I-V) of GARVs and to Korean human G9 strains (lineage III). These results show that porcine GARV infections are common in diarrheic piglets in South Korea. The infecting strains are genetically diverse, and include homologous (G5P[7]), heterologous (G8P[1]), and reassortant (G8P[7]), as well as emerging G9 GARV strains. PMID- 20359835 TI - Pulsed GnRH secretion and the FSH secretory peaks that initiate ovarian antral follicular wave emergence in anestrous ewes. AB - In ewes, immunization against GnRH blocks LH pulses but mean serum FSH concentrations are only partly reduced; the fate of the FSH peaks that precede ovarian follicular waves has not been studied. In this study, we used immunization against GnRH to examine the need for pulsed GnRH secretion in the genesis of FSH peaks in the anestrous ewe. Six anestrous ewes were given a GnRH immunogen on Day 0 and a booster injection on Day 28. Control ewes (n=6) received adjuvant only. Transrectal ultrasonography was performed daily for 2 days prior to and 10 days following both the primary (Days -2 to 10) and booster (Days 26 38) injections and for a 13-day period beginning 26 days after booster injection (Days 54-66). Blood samples were collected daily. Intensive bleeding (every 12min for 7h) was performed on Days 9, 37, and 65 of the experimental period to characterize the pulsatile pattern of LH secretion. GnRH antibody titers were increased and LH pulses were abolished immediately after booster immunization (P<0.05). The number of FSH peaks, FSH peak concentration and amplitude and basal FSH concentrations were only decreased in immunized ewes in the period of observations starting 26 days after booster immunization (P<0.05); however, some peaks were still seen. The number of follicular waves was decreased in the period around booster immunization and no follicular waves were seen during the period starting 26 days after booster immunization in immunized ewes (P<0.05). In summary, in anestrous ewes, when pulsed LH secretion was abolished by immunization against GnRH, the peaks in serum concentrations of FSH that trigger ovarian follicular waves continued for a period of time. We concluded that although blocking the effects of GnRH gradually causes a diminution of FSH secretion, there is no acute requirement for GnRH in the regulation of FSH peaks. The existence of FSH peaks in the absence of follicular waves, and pulsed LH secretion, suggests that some endogenous rhythm may drive the occurrence of FSH peaks, independent of both changes in negative feedback by secretory products from ovarian antral follicles and GnRH. PMID- 20359836 TI - Bayesian estimation of optimal craniofacial reconstructions. AB - Forensic craniofacial reconstruction (CFR) aims at estimating the facial outlook associated to an unknown skull for victim identification. Computerized CFR techniques are essentially a virtual mimicking of manual CFR techniques and all share the same conceptual model-based framework. We propose a fully automated Bayesian based statistical framework estimating the most probable face, according to a known craniofacial model (CFM), given the, possibly inaccurate, skull data. A multivariate Gaussian distribution is assumed for the shape parameters of the CFM, only allowing face-like solutions. The CFM is improved by encoding tissue depth differently as an extra value for 52 landmarks on the face and by incorporating gray-valued texture information. A fully automated and consistent technique is obtained by the use of an implicit target skull representation (TSR). The most plausible face associated to the target skull is calculated using an expectation-maximization procedure that is robust to small (noise) and/or gross errors (outliers). A clinical database of 12 individuals is used for simulating realistic reconstruction scenarios. Validation is performed in terms of reconstruction accuracy and recognition success. Within the same EM reconstruction framework, the proposed procedure is compared to alternative reconstructions using different target skull representations and different CFMs incorporating various amounts of covariance. The results indicate that the proposed CFM performs better than the other models. Furthermore, the use of the implicit TSR generates more consistent and better results compared to a realistic landmark based skull representation. Finally, these results also confirm that the Bayesian framework formulation is indeed robust against noise and outliers in the skull data. PMID- 20359837 TI - Computerized craniofacial reconstruction: Conceptual framework and review. AB - When confronted with a corpse that is unrecognizable due to its state of decomposition, soft-tissue mutilation or incineration, and if no other identification evidence is available, craniofacial reconstruction (CFR) can be a useful tool in the identification of the body. Traditional methods are based on manual reconstruction by physically modelling a face on a skull replica with clay or plasticine. The progress in computer science and the improvement of medical imaging technologies during recent years has had a significant impact on this domain. New, fast, flexible and computer-based objective reconstruction programs are under development. Employing the newer technologies and permanently evaluating the obtained results will hopefully lead to more accurate reconstructions, beneficial to the added value of CFR methods during crime-scene investigations. A general model-based workflow is observed, when analysing computerized CFR techniques today. The main purpose of this paper is to give an overview of existing computer-based CFR methods up to date defined within a common framework using a general taxonomy. The paper will also discuss the various alternatives and problems which arise during the process of designing a CFR program. PMID- 20359838 TI - Targeting specific facial variation for different identification tasks. AB - A conceptual framework that allows faces to be studied and compared objectively with biological validity is presented. The framework is a logical extension of modern morphometrics and statistical shape analysis techniques. Three dimensional (3D) facial scans were collected from 255 healthy young adults. One scan depicted a smiling facial expression and another scan depicted a neutral expression. These facial scans were modelled in a Principal Component Analysis (PCA) space where Euclidean (ED) and Mahalanobis (MD) distances were used to form similarity measures. Within this PCA space, property pathways were calculated that expressed the direction of change in facial expression. Decomposition of distances into property-independent (D1) and dependent components (D2) along these pathways enabled the comparison of two faces in terms of the extent of a smiling expression. The performance of all distances was tested and compared in dual types of experiments: Classification tasks and a Recognition task. In the Classification tasks, individual facial scans were assigned to one or more population groups of smiling or neutral scans. The property-dependent (D2) component of both Euclidean and Mahalanobis distances performed best in the Classification task, by correctly assigning 99.8% of scans to the right population group. The recognition task tested if a scan of an individual depicting a smiling/neutral expression could be positively identified when shown a scan of the same person depicting a neutral/smiling expression. ED1 and MD1 performed best, and correctly identified 97.8% and 94.8% of individual scans respectively as belonging to the same person despite differences in facial expression. It was concluded that decomposed components are superior to straightforward distances in achieving positive identifications and presents a novel method for quantifying facial similarity. Additionally, although the undecomposed Mahalanobis distance often used in practice outperformed that of the Euclidean, it was the opposite result for the decomposed distances. PMID- 20359839 TI - Efficacy and tolerability of levetiracetam in children with epilepsy. AB - OBJECTIVE: To assess the efficacy and tolerability of levetiracetam (Lev) in children with epilepsy. METHODS: Open-label observational, prospective, single arm, non-interventional study examining patients (<=14 years) with epilepsy, receiving mono- or combination therapy with levetiracetam. Levetiracetam was started at a dose of approximately 10mg/kg/day. The dose was titrated up with 10mg/kg increments if seizures were poorly controlled but the maximum daily dose could not be more than 60 mg/kg/day. Documented were seizure type and frequency, levetiracetam dose and side effects. RESULTS: 120 patients (39.3% females, mean age 4.5 +/- 3.9 years) were enrolled. Average duration of follow-up was 10.3 +/- 3.5 months. At study endpoint, 64.8% of patients got seizure free and 83.0% got a seizure reduction of >=50%. Observed side effects were somnolence, dysphoria, nervousness, dystrophy, somnipathy, asitia, debilitation, etc. and the incidence rate in the study was 47.5%. Four (3.3%) of 120 patients withdrew because of intolerance of side effects. The estimated one year retention rate of levetiracetam was 73.3%. Poor effect was the most common reason for withdrawal. CONCLUSIONS: In our study, it seemed that levetiracetam was safe and effective for a wide range of epileptic seizures in children with epilepsy. PMID- 20359840 TI - Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study. AB - A series of synthesised tocainide analogues were characterized for their human serum albumin (HSA) binding, using high-performance liquid affinity chromatography (HPLAC) and circular dichroism (CD). The synthesis and physico chemical characterization of compounds 7a-7d is reported here. For the HPLAC investigation HSA was covalently immobilized to the silica matrix of the HPLC column, using an anchoring procedure, which allows the binding properties of the protein to be maintained. The HSA-based column was used for getting information on the high affinity binding sites of the tocainide analogues to HSA. According to the displacement chromatography approach, the retentions of the analytes were determined in the absence and in the presence of increasing concentrations of competitors known to bind to specific binding sites on the protein. The same system, drug/protein, was investigated in solution by CD. The analysed compounds, proved active as sodium channel blockers, showed a much higher affinity to the serum carrier with respect to the parent compound, tocainide. Further, a non cooperative interaction at sites I and II, and an almost independent binding at the bilirubin binding site on HSA were hypothesised on the bases of the competition experiments. PMID- 20359841 TI - Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma. AB - The effect of repeated consumption of virgin olive oil on endogenous phenolic metabolites of fasting plasma is unknown. For this reason, we hypothesized that regular long-term virgin olive oil intake could have an indirect protection effect on the endogenous phenols. Thus, the aim of the study was to determine the phenolic profile of human plasma in a fasting state of long-term regular virgin olive oil consumers, using the fasting plasma of non-consumers as a natural control. Forty participants living in the area of Reus (Catalonia, Spain) were selected, 20 life-long regular consumers of virgin olive oil and a natural control of 20 non-consumers, the latter being Rumanians who dislike the taste of olive oil. The diet was obtained from 3-day food records. The results showed similar phenolic composition of fasting plasmas of the two volunteer groups. Of special interest is that more of the compounds quantified showed higher concentration in fasting plasma from habitual virgin olive oil consumers. The compounds were semi-quantified using caffeic acid as the calibration standard. The quantification of fasting consumer's plasma showed higher concentration of a hydroxyflavanone type compound (2.90+/-0.04 microM vs 1.5+/-0.04 microM) and a catecholamine derivative (0.70+/-0.03 microM vs 0.56+/-0.03 microM) than the plasma of non-consumers (P<0.05). The results suggest an indirect protective mechanism of long-term regular virgin olive oil consumption related to the protection of the endogenous antioxidant system. PMID- 20359842 TI - Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. AB - OBJECTIVES: This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk. BACKGROUND: Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences. METHODS: Individual patient data, with 5-year outcomes, were obtained from FRISC II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived. RESULTS: Over 5 years, 14.7% (389 of 2,721) of patients randomized to an RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI strategy), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in highest-risk patients. CONCLUSIONS: An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients. PMID- 20359843 TI - Double-blind injectable hydromorphone versus diacetylmorphine for the treatment of opioid dependence: a pilot study. AB - Using data from the North American Opioid Maintenance Initiative study, a Phase III randomized and parallel arm trial, this pilot study is aimed at testing if treatment response with injectable hydromorphone differs compared to diacetylmorphine in the treatment of long-term opioid addiction. A total of 140 long-term, treatment-refractory opioid-dependent individuals received either injectable diacetylmorphine (n = 115) or hydromorphone (n = 25), in a double blind fashion, over 12 months. At the end of the study, none of the participants in the hydromorphone group thought they were definitely receiving this drug. Retention rates at 12 months with diacetylmorphine (87.8%; 95% confidence interval [CI] = 80.5%-92.7%) and hydromorphone (88.0%; 95% CI = 68.7%-96.1%) were virtually identical. The use of illicit heroin in the prior month declined from a mean of 26.6 and 26.3 days at baseline to 5.3 and 5.2 days at 12 month in the diacetylmorphine and hydromorphone groups, respectively. There were no differences between diacetylmorphine and hydromorphone in the adjusted mean scores of the European Addiction Severity Index. There were no differences in the safety profile of the medications. Hydromorphone may be similarly safe and effective as diacetylmorphine as opioid-agonist substitution treatment; future studies are required to confirm it. Further study will also be required to show that open-label hydromorphone can also successfully attract patients into care and retain them. PMID- 20359844 TI - Letter: the mechanisms of failure of totally implantable central venous access system: Analysis of 73 cases with fracture of catheter (EJSO 2010; 36:100-3). PMID- 20359845 TI - [Perioperative psychobehavioural changes in children]. AB - The relevant literature since the 1940s has been collected from the Medline database, using the keywords: child, operation, anxiety, distress, postoperative complications, preparation, premedication, parental presence, prevention. Preoperative anxiety, emergence delirium, and postoperative behavior changes are all manifestations of psychological distress in children undergoing surgery. Preoperative anxiety is most prominent during anaesthesia induction. Emergence delirium is frequent and somewhat independent of pain levels. Postoperative behavior changes most often include separation anxiety, tantrums, fear of strangers, eating problems, nightmares, night terrors and bedwetting. These difficulties tend to resolve themselves with time but can last up to one year in some children. The major risk factors for postoperative behavior problems are young age, prior negative experience with hospitals or medical care, certain kinds of hospitalization, postoperative pain, parental anxiety, and certain personality traits of the child. Currently, tools exist for quantifying anxiety (m-YPAS) and postoperative behavior (PHBQ). It is possible to identify those children who are at risk for postoperative complications during the preanaesthesia consultation by paying close attention to children under six years with higher levels of emotionality and impulsivity and poorer socialization skills with anxious parents. Suggested strategies for reducing child distress include preoperative preparation, premedication, parental presence during anaesthesia induction, and interventions affecting the child's environment, such as hypnosis. There are numerous ways to provide preoperative preparation (information, modeling, role playing, encouraging effective coping) and their effectiveness is proven in the preoperative setting but not during anaesthesia induction or in the operating room. Midazolam has been shown to be an effective preoperative sedative for reducing anxiety. Parental presence during induction has been shown to effectively reduce preoperative anxiety in children in certain contexts (when the parent is calm and the child is anxious). It is worthwhile if it is integrated into a family-centered anxiety management program and remains one of several options offered to families. Overall, taking into account the child's psychological needs should be considered an essential part of paediatric anaesthesia. Tools and techniques are available for assessing and managing the perioperative distress experienced by children. PMID- 20359846 TI - [Anaphylactic shock after injection of antitetanus serum]. PMID- 20359847 TI - Taurine deficiency in thalassemia major-induced osteoporosis treated with neridronate. AB - The aetiology of thalassemia major-induced osteoporosis is multifactorial. Up to now, bisphosphonates seem to be a promising therapy. Taurine is found in a high concentration in bone cells enhancing bone tissue formation and inhibiting bone loss. Recently we found a decrease taurine plasma level in children affected by osteogenesis imperfecta during neridronate (amino-bisphosphonate) therapy suggesting a possible interaction between pharmacological effect of this drug and taurine availability. On the basis of these results, we performed plasma and urine amino acid (AA) analysis in thalassemia major-induced osteoporosis before and after 12 months of neridronate treatment. Twelve patients, five males and seven females, aged from 20 to 29 years following a hypertransfusion treatment protocol were enrolled in the study. Patients were treated with neridronate infusion every one month (30 mg in 100ml of saline). Plasma and urine specimens for AA analysis, bone mineral density, bone mineral content and vertebral project area were examined at baseline (T0) and after 12 months of treatment (T12). A significant decrease was observed for plasma level and urinary excretion of taurine (T0 vs. T12=p<0.01) whereas bone mineral content and vertebral projection area showed a statistical significant increase (T0 vs. T12=p<0.05). These results and other experimental researches warrant further studies examining the long-term effect of taurine supplementation in association with neridronate treatment. PMID- 20359848 TI - Inhibition of type III TGF-beta receptor aggravates lung fibrotic process. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell proliferation, death, development or differentiation. In addition, TGF-beta is considered a key mediator in fibrogenic processes, and signals either directly or indirectly through types I, II and III (TbetaRI, II, and III) receptor complexes. The type III TGF-beta (TbetaRIII or betaglycan) is a transmembrane proteoglycan without a functional kinase domain, and is considered as a coreceptor to increase the affinity of ligand binding to TbetaRII. Little is studied on TGF-beta and TbetaRIII (or betaglycan) signaling, while it is well known about TGF-beta ligand and TbetaRII signaling. In this study, we investigated the effects of TbetaRIII expression on TGF-beta induced differentiation, in view of the finding that TbetaRIII is significantly downregulated during TGF-beta-induced differentiation in fibroblasts. TGF-beta induced alpha-SMA and Procollagen Type I expression were markedly inhibited in fibroblasts stably expressing TbetaRIII. Endogenous TbetaRIII expression did not alter the TbetaRI or TbetaRII levels, but inhibited Smad 2/3, Akt and ERK phosphorylation. The molecular mechanism of TbetaRIII action in TGF-beta-induced differentiation is associated with both Smad-dependent and Smad-independent pathways. Our results suggest that TbetaRIII is a novel molecular target for regulation of TGF-beta signaling in myofibroblast differentiation. PMID- 20359849 TI - Enzymes that hydrolyze adenine nucleotides in lymphocytes and platelets of immunosuppressed rats. AB - NTPDase (EC 3.6.1.5) is an enzyme that hydrolyzes extracellular nucleoside tri and/ or diphosphates to form ATP, which can serve as a substrate for ecto-5'- nucleotidase (EC 3.1.3.5), releasing adenosine, an inhibitor of platelet aggregation and an immunosuppressant agent. In this study, the activity of enzymes that hydrolyze adenine nucleotides was investigated in lymphocytes and platelets of immunosuppressed rats. NTPDase and ecto-5'-nucleotidase activities were determined by colorimetric assay with quantification of the inorganic phosphate released. A significant increase in NTPDase activity was observed in lymphocytes (about 30% in ATP hydrolysis and 80% in ADP hydrolysis, at p<0.05 and p<0.01, respectively). In platelets, there was a significant increase in 5' nucleotidase activity in immunosuppressed rats (p<0.01) when compared with controls. These results suggest that the hydrolysis of adenine nucleotides is modified in the immunosuppressed state, possibly to compensate for alterations that occur and to avoid the adverse effects of therapy. PMID- 20359850 TI - Interaction of Pdcd4 with eIF4E inhibits the metastatic potential of hepatocellular carcinoma. AB - Oxidative stress can contribute to the development of hepatocellular carcinoma (HCC) ability of the carcinoma. It has been found that oxidative stress stimulates the phosphorylation of eIF4E primarily through mitogen-activated protein kinase (MAPK) pathways resulting in increased protein translation. Utilizing specific inhibitors of MAPK pathways (SP600125 for c-Jun amino-terminal kinases [JNKs], PD098059 for extracellular signal-regulated kinases [ERKs], and SB203580 for p38 MAPK), we determined that it is primarily the inhibition of JNK that results in the suppression of the increase of p-eIF4E. We also found that PDCD4 inhibits JNK activity resulting in inhibition of the phosphorylation of c Jun, one isoform of AP-1. We demonstrated that transfection with PDCD4 or inhibition of JNK by SP600125 alters the expression and phosphorylation of eIF4E in the presence of H(2)O(2). PDCD4 results in a stronger inhibitory effect than SP600125. PMID- 20359851 TI - Are treatment options related to alexithymia in eating disorders? Results from a three-year naturalistic longitudinal study. AB - OBJECTIVE: Longitudinal studies have shown that alexithymic features can interfere with treatment response in eating disorders. However, an alternative hypothesis could be that clinicians faced with alexithymic patients chose different treatment options according to their perceptions of these patients. The aim of this investigation was to explore the relationships between alexithymic features and treatment options provided by professionals in a naturalistic prospective study of eating disorders. METHODS: We conducted a 3-year longitudinal study exploring a sample of 102 DSM-IV Eating Disorder patients with the Toronto Alexithymia Scale (TAS-20). All treatments received during follow-up were recorded and recoded dichotomously, and crossed with the variation of alexithymic categories (cut-off>=56) between inclusion and follow-up. RESULTS: Patients received different treatments according to their alexithymic profile, in terms both of number and type of treatment received. Patients with high, stable levels of alexithymia received overall more treatments, and significantly more antidepressants, than non-alexithymic patients. Patients who became alexithymics during follow-up were more often rehospitalized and received fewer regular psychotherapies than the non-alexithymic patients. CONCLUSIONS: Professionals should carefully monitor these personality features and be aware of the potential impact of alexithymic features on treatment compliance and on treatment choice for eating disordered patients. PMID- 20359852 TI - Expression of peptide NAP in rat retinal Muller cells prevents hypoxia-induced retinal injuries and promotes retinal neurons growth. AB - NAP (NAPVSIPQ) is a short peptide derived from activity-dependent neuroprotective protein (ADNP) sequence, whose potent and direct neuroprotective capabilities have been widely accepted. However, due to the high risk and inconvenience of intraocular injections, NAP is difficult to be clinically administered as therapeutic agent in treating retinal diseases. Currently, stable transfection of this octapeptide into cells has not been reported, partly because of its small size and lacking of 5' signal sequence. Here, we have developed a novel NT4-NAP fusion gene by attaching the 5' nonfunctional preproregion of neurotrophin 4 (NT4) to NAP cDNA. Recombinant adeno-associated virus was established to introduce NT4-NAP construct into cultured rat retinal Muller cells (RMC), resulting in sustained high level NAP production from stable transfection. Functional analyses of RMC cells transfected with NAP revealed the remarkably reduced cytotoxicity and apoptosis of the cells under hypoxia. Furthermore, coculturing of transfected RMC-NAP cells with primary rat retinal neural cells offer marked protection to the latter against hypoxia induced cellular damages. Together our data indicate that stable transfection of NAP into retinal Muller cells with constant NAP production is possible. NAP produced from cellular transfection maintained its biological neuroprotective activities. This targeted gene expression may provide an effective treatment for retinal diseases in the near future. PMID- 20359853 TI - Developmental delay associated with normal thyroidal function and long-term amiodarone therapy during fetal and neonatal life. AB - We reported a case of a child with neurodevelopment delay induced by long-term amiodarone exposure due to a treatment of fetal supraventricular tachycardia (FSVT), subtype permanent junctional reciprocating tachycardia (PJRT) with the normal thyroidal function. Refractory persistent FSVT was treated intrautero with digoxin (0.5 mg QD) until delivery and amiodarone (100 mg QD) from 26 to 35 weeks of gestation. A baby weighing 3550 g with normal acid-base status was delivered at 38 weeks of gestation. The PJRT recurred 28 hours after delivery and reverted to sinus rhythm with amiodarone and propranolol for another 24 months. The neurological disturbances were manifested at the age of 12 months, when hypotonia and delayed motor milestones were recognised. At the age of 18 months, the child had mildly neurological development delay with hypotonia, ataxia and foot deformities. At the age of 24 months, motor milestones were mildly delayed with the usage of a few words without the ability to connect them into the sentence. The developmental quotient (DQ) was 68. Electroencephalogram and magnetic resonance imaging of the central nervous system were all normal. At the age of 30 months, motor milestones were still delayed together with speech development and language delay, only some words were used, not distinctly, DQ was 78. Thyroid function was normal on each examination. All blood and urine analyses were in normal ranges. Chromosome analysis did not show any abnormalities. Since we excluded all possible reasons, we could only bring an indirect link between the long-term amiodarone exposure during fetal and postnatal life and neurodevelopment delay. PMID- 20359854 TI - Effect of low molecular weight heparin rectal suppository on experimental ulcerative colitis in mice. AB - The objective of this study was to investigate the effect and possible mechanism of rectally administered low molecular weight heparin (LMWH) on experimental ulcerative colitis. LMWH rectal suppository was prepared and its efficacy was studied by macroscopical and histological scoring systems as well as myeloperoxidase activity. Serum levels, including tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) and a link factor of blood coagulation and inflammation factor Xa (FXa) were assayed by enzyme-linked immunosorbent assay. The expression of Musashi-1 (as an intestinal stem cell marker) in the colons was assessed by immunohistochemical analysis. The results showed that LMWH rectal suppository significantly decreased serum levels of TNF-alpha, IL-6 as well as FXa, while increased the expression of Musashi-1 in colon compared with acetic acid induced ulcerative colitis model group. All these preliminary results indicate LMWH rectal suppository is promising for treatment of ulcerative colitis. PMID- 20359855 TI - The mechanisms of somatostatin induced enhanced chemosensitivity of gallbladder cancer cell line to doxorubicin: cell cycle modulation plus target enzyme up regulation. AB - BACKGROUND: Gallbladder carcinoma is known to be an aggressive malignancy and nonsensitive to routine chemotherapy. Its prognosis is quite poor. We have illustrated that somatostatin (SST) can enhance chemosensitivity of gallbladder cancer to Doxorubicin (DOX) in our precious studies. Here, we explored the possible mechanisms by which SST used to enhance the cytotoxicity of DOX on gallbladder carcinoma cell line. METHODS: Human gallbladder cancer cells line (GBC-SD cell line) were divided into four groups: control group, SST group, DOX group, SST+DOX co-treated-group. Cell cycle was detected by flow cytometry (FCM). Cell apoptosis index was detected by using Annexin V/Propidium Iodide Binding on FCM. The expressions of certain key cell cycle-related factors, including retinoblastoma protein (Rb) and E2F-1 protein were investigated by western blotting. ICBP90 protein, which could be a new downstream effector of E2F-1, was also detected by western blotting. The expression of Topo IIalpha protein, target enzyme of DOX, was assessed in synchronized GBC-SD cells by western blotting. RESULTS: After 24h treatment with SST alone, cell cycle was arrested at S phase in GBC-SD cells line, followed by indistinctive increment of apoptosis index. After 24h treatment with SST and DOX, apoptosis index significantly increased than that of DOX alone (P<0.05). Compared with control group, the expressions of Rb and E2F-1 protein were significantly up-regulated at 24h after treatment with SST. Similarly, the expressions of ICBP90 and Topo IIalpha protein were also enhanced at 24h after treatment with SST. CONCLUSION: These results suggested that SST could induce cell cycle block in S phase in GBC-SD cells line, the most sensitive phase of the cell cycle for DOX, through up-regulating Rb, E2F-1 and ICBP90 protein expression. Furthermore, ICBP90 induced the enhanced expression of Topo IIalpha protein which is the target enzyme of DOX and enhanced its cytotoxic effect on GBC-SD cells. We concluded that the mechanisms of SST enhanced chemosensitivity of GBC-SD cell line to DOX might be cell cycle arrest plus up regulated target enzyme. PMID- 20359856 TI - Preclinical pharmacokinetic analysis of NOV-002, a glutathione disulfide mimetic. AB - NOV-002 is a glutathione disulfide (GSSG) mimetic that is the subject of clinical investigation in oncology indications. GSSG is reduced by glutathione reductase (GR) to form glutathione (GSH), thereby maintaining redox homeostasis. The purpose of the study was to report the pharmacokinetic properties of NOV-002 and evaluate the effect that NOV-002 elicits in redox homeostasis. The pharmacokinetic analysis and tissue distribution of NOV-002 and GSH was evaluated in mice following a dose of 250 mg/kg, i.p. The redox potential and total protein thiol status was calculated. Here we show that NOV-002 is a substrate for GR and that GSH is a primary metabolite. Non-linear pharmacokinetic modeling predicted that the estimated absorption and elimination rate constants correspond to a half life of approximately 13 min with an AUC of 1.18 MUgh/mL, a C(max) of 2.16 MUg/ml and a volume of distribution of 42.61 L/kg. In addition, measurement of the redox potential and total protein thiol status indicated the generation of a transient oxidative signal in the plasma compartment after administration of NOV-002. These results indicate that NOV-002 exerts kinetic and dynamic effects in mice consistent with the GSSG component as the active pharmacological constituent of the drug. A longer-lasting decrease in total plasma free thiol content was also seen, suggesting that the oxidative effect of the GSSG from NOV-002 was impacting redox homeostasis. PMID- 20359857 TI - Characterization of a GSK-3 inhibitor in culture of human cord blood primitive hematopoietic cells. AB - Wnt signaling pathway plays important roles in the biology of stem cells in maintaining their self-renewal property. Glycogen synthase kinase-3 (GSK-3) inhibitors, the Wnt signaling agonists, maintain the pluripotency of embryonic stem cells. We report here that a synthetic GSK-3 inhibitor, 6-bromoindirubin-3' oxime (BIO), showed opposite effects on the expansion of human primitive hematopoietic cells isolated from umbilical cord blood (UCB). In combination with human c-kit ligand (KL), BIO at low concentration (0.2 MUM) enhanced the expansion of UCB CD34+ cells, which was BIO structure and exposure time dependent; however, at high concentration (2 MUM) it inhibited the expansion of the cells. Furthermore, hematopoietic stem cells (HSCs) were exhausted when the UCB CD34+ cells were exposed to 0.2 MUM BIO and KL longer than 2 days. In conclusion, the use of BIO in expansion of UCB HSCs remains a significant challenge. PMID- 20359858 TI - Therapeutic efficacy of experimental rheumatoid arthritis with low-dose methotrexate by increasing partially CD4+CD25+ Treg cells and inducing Th1 to Th2 shift in both cells and cytokines. AB - Low-dose methotrexate (MTX), a traditional folate antagonist and disease modifying antirheumatic drug administered weekly either alone or as combination therapy, is widely accepted as the gold standard in rheumatoid arthritis (RA) treatment. Although its mechanism of action in RA is still poorly understood, MTX potentially acts via antiproliferative, anti-inflammatory, and/or immunosuppressive means. The therapeutic mechanisms and efficacy of low-dose MTX and the oral tolerance protein natural chicken type II collagen (nCCII) were compared in vitro and in vivo using an established collagen-induced arthritis (CIA) rat model. We used clinical visual scoring, radiographic X-ray analysis, histopathological examination, and sera anti-CII IgG measurements to determine the severity of disease with and without treatment. Low-dose MTX had significant clinical therapeutic efficacy against established CIA. Similar to nCCII, MTX mediated CIA by specific immunotolerant effects and not by nonspecific immunosuppression. The mechanism underlying the therapeutic efficacy could be at least partially attributed to the increased production of CD4+CD25+ Treg cells. These cells specifically downmodulated the T lymphocyte proliferative response to CCII but not PHA, induced a Th1-to-Th2 shift, downregulated Th1 cytokines, and upregulated both Th2 and Th3 cytokines. To the best of our knowledge, this is the first demonstration that low-dose MTX probably serves as a potent inducer of specific immunotolerance but not of nonspecific immunosuppression in the treatment of RA. PMID- 20359859 TI - Carvedilol ameliorates sympathetic nerve sprouting and electrical remodeling after myocardial infarction in rats. AB - BACKGROUND: We hypothesized that carvedilol, a nonselective beta-blocker, can exert antiarrhythmogenic effects by inhibiting sympathetic nerve sprouting and electrical remodeling at peri-infarct zones after myocardial infarction (MI). METHODS: MI was induced by ligation of the coronary artery. The rats in the carvedilol group received 5.0mg/kg carvedilol twice a day. Eight weeks after MI, monophasic action potential duration (MAPD), effective refractory period (ERP) and the inducibility of ventricular arrhythmia at the peri-infarct zones were evaluated and compared with MI rats. After these studies, the expression of growth associated protein 43 (GAP43) and tyrosinehydroxylase (TH) at the peri infarct zones were examined by western blot and RT-PCR analysis. RESULTS: Eight weeks after surgery, carvedilol shortened the duration of the MAPD determined as 20% (MAPD(20)) and 90% (MAPD(90)) repolarization time (33 +/- 9 ms and 110 +/- 18 ms vs 21 +/- 6 ms and 76 +/- 13 ms, both P<0.05) and ERP (76 +/- 15 ms vs 62 +/- 12 ms, P<0.05), respectively. Carvedilol decreased the inducibility of ventricular arrhythmia after MI (76% vs 32%, P<0.05). The expression of GAP43 and TH were suppressed by carvedilol after MI. CONCLUSION: Carvedilol exerts antiarrhythmogenic effects by ameliorating sympathetic nerve sprouting and electrical remodeling in MI rats. The effects of carvedilol on amelioration of electrical remodeling may be partly related to the inhibition of sympathetic remodeling. PMID- 20359860 TI - [Autoimmune hemolytic anemia: An unusual revelation of human immunodeficiency virus]. PMID- 20359861 TI - Comparison of voice-use profiles between elementary classroom and music teachers. AB - Among teachers, music teachers are roughly four times more likely than classroom teachers to develop voice-related problems. Although it has been established that music teachers use their voices at high intensities and durations in the course of their workday, voice-use profiles concerning the amount and intensity of vocal use and vocal load have neither been quantified nor has vocal load for music teachers been compared with classroom teachers using these same voice-use parameters. In this study, total phonation time, fundamental frequency (F0), and vocal intensity (dB SPL [sound pressure level]) were measured or estimated directly using a KayPENTAX Ambulatory Phonation Monitor (KayPENTAX, Lincoln Park, NJ). Vocal load was calculated as cycle and distance dose, as defined by Svec et al (2003), which integrates total phonation time, F0, and vocal intensity. Twelve participants (n = 7 elementary music teachers and n = 5 elementary classroom teachers) were monitored during five full teaching days of one workweek to determine average vocal load for these two groups of teachers. Statistically significant differences in all measures were found between the two groups (P < 0.05) with large effect sizes for all parameters. These results suggest that typical vocal loads for music teachers are substantially higher than those experienced by classroom teachers (P < 0.01). This study suggests that reducing vocal load may have immediate clinical and educational benefits in vocal health in music teachers. PMID- 20359862 TI - A meta-analysis of outcomes of hydration intervention on phonation threshold pressure. AB - OBJECTIVES: Vocal fold hydration is purported to promote optimal biomechanical characteristics of vocal fold mucosa, increase efficiency of vocal fold oscillation, and enhance voice quality. The purpose of this work was to determine the magnitude and consistency of the effect of vocal fold hydration on vocal fold function across published clinical studies. METHODS: We completed a comprehensive meta-analysis of the effects of superficial and systemic vocal fold hydration on phonation threshold pressure (PTP), a measure of efficiency of voice production. RESULTS: We identified 34 studies that examined the effects of hydration on vocal function. Of these studies, 14 examined the effects of hydration on PTP. Nine of these articles met the criteria for inclusion in this analysis. We observed an average effect size of 0.33, indicating that, overall, hydration treatment demonstrated a tendency to reduce PTP. However, this decrease in phonatory effort did not reach significance at the 95% confidence level. The effects of hydration intervention varied considerably across studies (-0.19 to 3.96). We considered that two factors, pitch level of the task and vocal health of participants, may have contributed to this variability in findings. However, our analysis found that these factors could not account for differences in effect size. CONCLUSION: To understand the variability in outcomes across studies, the role of factors that may impact the effects of hydration, such as the amount, type, and duration of intervention, must be determined. Only then can we obtain data to guide best clinical practice for protecting and rehabilitating vocal function. PMID- 20359863 TI - Voice-related complaints in the pediatric population. AB - Subjective evaluation of the voice by the patient is routinely assessed in the adult dysphonic population; this is, however, not the case in the pediatric population. There were three objectives of this study: the first goal was to study the ability of children aged 5-13 years to express themselves about physical, emotional, and sociofunctional aspects of their voice. The second goal was to explore if specific voice-related complaints were expressed by dysphonic children as compared with normophonic children. The third goal was to compare the dysphonic children's voice-related complaints with those of their mothers. The overall objective was to set the grounds for the elaboration of a standardized questionnaire in French concerning subjective evaluation of voice in children. Twenty-five dysphonic children with vocal complaint (15 nodules, one polyp, one microweb, eight unspecified) and 55 normophonic children aged 5-13 years were interviewed. The interviews were semistructured based on a canvas of voice related questions. The dysphonic children's mothers were interviewed with the mean of a written questionnaire and were invited to discuss their answers orally with the examiner. The results were analyzed qualitatively and statistically. A Chi-square test and the Fisher's test were used to analyze the differences between the complaints expressed by the dysphonic and the normophonic children, and a binomial test was used to compare the children's answers with their mothers' answers. The qualitative analysis of the interviews suggests that children are capable of reflecting over their own voice and of giving autonomous information about different aspects of their voice. It also appeared that voice is a complex phenomenon and that it needs to be clearly and cautiously defined to the children. We identified 27 different complaints related to the voice, out of which 17 were significantly more expressed by dysphonic than by normophonic children (P<0.05). Three of the 27 identified complaints show significant discordances between the mothers and the dysphonic children. The results suggest that children are capable of making a subjective and autonomous evaluation of their voice and that dysphonic children experience significantly more voice related discomfort than nondysphonic children. The complaints expressed by the dysphonic children and their mothers are not all in concordance. The main conclusion is that a standardized subjective evaluation of the voice, not only by the parents but also by the child him/herself, would be relevant in the assessment of pediatric dysphonia. PMID- 20359864 TI - Experimental analysis of the characteristics of artificial vocal folds. AB - Specialized literature presents a number of models describing the function of the vocal folds. In most of those models, an emphasis is placed on the air flowing through the glottis and, further, on the effect of the parameters of the air alone (its mass, speed, and so forth). The article focuses on the constructional definition of artificial vocal folds and their experimental analysis. The analysis is conducted for voiced source voice phonation and for the changing mean value of the subglottal pressure. The article further deals with the analysis of the pressure of the airflow through the vocal folds, which is cut (separated) into individual pulses by the vibrating vocal folds. The analysis results show that air pulse characteristics are relevant to voice generation, as they are produced by the flowing air and vibrating vocal folds. A number of artificial vocal folds have been constructed to date, and the aforementioned view of their phonation is confirmed by their analysis. The experiments have confirmed that man is able to consciously affect only two parameters of the source voice, that is, its fundamental frequency and voice intensity. The main forces acting on the vocal folds during phonation are as follows: subglottal air pressure and elastic and inertia forces of the vocal folds' structure. The correctness of the function of the artificial vocal folds is documented by the experimental verification of the spectra of several types of artificial vocal folds. PMID- 20359865 TI - Low wall velocity of left atrial appendage measured by trans-thoracic echocardiography predicts thrombus formation caused by atrial appendage dysfunction. AB - BACKGROUND: Atrial fibrillation is associated with ischemic stroke because of thrombi that form within the left atrial appendage (LAA). The aim of this study was to develop a new parameter for LAA function that is easily performed using transthoracic echocardiography (TTE). METHODS: TTE and transesophageal echocardiography were performed in 106 patients with stroke. LAA wall motion velocity (TTE-LAWV) was measured using Doppler tissue imaging at the LAA tip. RESULTS: TTE-LAWV was significantly lower in patients with atrial fibrillation and LAA thrombus than in those with atrial fibrillation and no LAA thrombus and in sinus rhythm (7.5 +/- 1.9 vs 10.0 +/- 3.4 and 13.8 +/- 5.7 cm/s, respectively, P < .05). TTE-LAWV was significantly correlated with LAA emptying flow velocity (R = 0.462, P < .05). The multivariate logistic regression analysis showed that TTE-LAWV < 8.7 cm/s was an independent predictor of LAA thrombus formation (odds ratio, 9.473; 95% confidence interval, 1.172-76.55; P < .05). CONCLUSION: TTE LAWV can noninvasively evaluate LAA dysfunction and assist in the detection of LAA thrombus. PMID- 20359866 TI - Sydenham society: 2009. PMID- 20359867 TI - Gingival angiosarcoma mimicking necrotizing gingivitis. AB - The authors present a case of a rare highly malignant condition that initially appeared clinically and histologically to be the relatively common and benign condition necrotizing gingivitis. Conditions that do not follow the expected clinical course mandate further investigation because rare malignant disease is not foremost in the mind of dentists and oral and maxillofacial surgeons. PMID- 20359868 TI - Involvement of histamine 1 receptor in seizure susceptibility and neuroprotection in immature mice. AB - The central histaminergic neuronal system is a powerful modulator of brain activity, and its functional disturbance is related to e.g. epilepsy. We have recently shown in the slice culture system that histaminergic neurons attenuate kainic acid (KA)-induced epileptiform activity and neuronal damage in the hippocampus through histamine 1 (H1) receptors. We now further examined the role of H1 receptors in the regulation of KA-induced seizures and neuronal damage in immature 9-day-old H1 receptor knock out (KO) mice. In the H1 receptor KO mice, behavioral seizures were significantly more severe and duration of seizures was significantly longer when compared to the wild type (WT) mice at the KA dose of 2mg/kg. Moreover, neuronal damage correlated with seizure severity, and it was significantly increased in the thalamus and retrosplenial granular cortex (RGC) of the KO mice. The H1 receptor antagonist triprolidine treatment supported these findings by showing significantly increased seizures severity and neuronal damage in the septum, thalamus, CA3 region of the hippocampus, and RGC in the KA-treated WT mice. Our present novel findings suggest that H1 receptors play a pivotal role in the regulation of seizure intensity and duration as well as seizure-induced neuronal damage in the immature P9 mice. PMID- 20359869 TI - Molecular characteristics of extended-spectrum beta-lactamase-producing Escherichia coli from the Chicago area: high prevalence of ST131 producing CTX-M 15 in community hospitals. AB - This study was designed to characterise 30 non-duplicate extended-spectrum beta lactamase (ESBL)-producing Escherichia coli clinical isolates from the community in the Chicago metropolitan area collected during 2008. The majority of isolates (n=28) were recovered from urine and 2 isolates were from blood. Molecular characterisation was done using the following techniques: isoelectric focusing; polymerase chain reaction (PCR) and sequencing of bla(ESBL); PCR for plasmid mediated quinolone resistance determinants; identification of ST131; phylogenetic grouping; and replicon typing. Genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE) with XbaI and repetitive sequence-based PCR (rep-PCR) typing. Twenty-six (87%) of the ESBL-producing E. coli were positive for bla(CTX M) genes (22 CTX-M-15 and 4 CTX-M-14), whilst the remaining 4 isolates produced SHV-2. Twenty-eight isolates (93%) were non-susceptible to ciprofloxacin and 16 (53%) were positive for aac(6')-Ib-cr. Overall, 16 (53%) of the ESBL-producers belonged to clonal complex ST131 that produced CTX-M-15 or CTX-M-14. Molecular characteristics of ST131 showed that it belonged to three distinct but related PFGE clones, was derived from phylogenetic group B2 and contained IncFII type plasmids. These results illustrate that E. coli clonal complex ST131 producing CTX-M-15, CTX-M-14, OXA-1, TEM-1 and aac(6')-Ib-cr has emerged as an important cause of community-onset urinary tract infections caused by ESBL-producing E. coli isolates in the Chicago area. PMID- 20359870 TI - Microbial biosurfactants and hydrolytic enzymes mediates in situ development of stable supra-molecular assemblies in fatty acids released from triglycerides. AB - The present study demonstrates in situ formation of multilamellar stable vesicles (MLSVs) of fatty acids released during the growth of microorganisms in the presence of triglycerides. Release of lipase during initial phase of growth hydrolyzes the triglycerides and release free fatty acids (mono or diglycerides) and glycerol. By extending the growth and the prevailing composition of media (unspent nutrients, salts, pH of the medium, biosurfactants, fatty acids, glycerol) and agitation transforms free fatty acids to MLSV of both cylindrical and spherical macroscopic structures via micelle formation with in 240h of incubation. Cross-sectional view and SEM analysis of macroscopic structures reveal the existence of continuous multilayering. Thermo-gravimetric analysis illustrates the stability of the vesicles. FT-IR analysis emphasizes the presence of amide linkages, responsible for self-assembly processes. Schematic representation of formation of MLSV demonstrated for further understanding. Additional exploration on MLSV formation in arteries and the relationship between MLSV and in situ plaque formation by the components of blood in the arteries are schematically explained and submitted as supporting information (SI-2). PMID- 20359871 TI - Chemotherapy followed by chemoradiotherapy for locally advanced non-metastatic pancreatic cancer - a new paradigm? PMID- 20359872 TI - Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver. AB - Nowadays, people's exposure to chemical compounds such as organophosphorus insecticides is continuously on the rise more and more. Theses compounds have induced an excessive production of free radicals which are responsible for several cell alterations in the organism. Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, we investigate the role of date palm fruit extract (Phoenix dactylifera L.) in protection against oxidative damage and hepatotoxicity induced by subchronic exposure to dimethoate (20mg/kg/day). Oral administration of dimethoate caused hepatotoxicity as monitored by the increase in the levels of hepatic markers enzymes (transaminases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase), as well as in hepatic malondialdehyde thus causing drastic alteration in antioxidant defence system. Particularly, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were found increased by dimethoate while catalase (CAT) activity was reduced significantly. These biochemical alterations were accompanied by histological changes marked by appearance of vacuolization, necrosis, congestion, inflammation, and enlargement of sinusoids in liver section. Pretreatment with date palm fruit extract restored the liver damage induced by dimethoate, as revealed by inhibition of hepatic lipid peroxidation, amelioration of SOD, GPx and CAT activities and improvement of histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress induced hepatotoxicity. PMID- 20359873 TI - Griffonia simplicifolia negatively affects sexual behavior in female rats. AB - At present Griffonia simplicifolia is used in food supplement aimed to treat mood disorders as well as to reduce food intake and body weight. The plant has gained increasing interest for its high content in 5-hydroxy-L-tryptophan (5-HTP) particularly in the seed. The present study was designed to evaluate the influence of a seed extract of the plant, dosed at 25, 50 and 100 mg/kg, on the sexual behavior of ovariectomized hormone-primed rats after acute and subchronic treatment. The single administration of G. simplicifolia significantly reduced lordosis response and increased rejection behavior in female rats treated with the highest dose while it did not influence proceptive behaviors. On the other hand the subchronic administration of the extract significantly reduced proceptivity but not receptivity, and increased rejection behavior. All the tested dosages were able to markedly decrease food intake and body weight after a 9-day treatment. Taken together the present results, possibly ascribed to increased levels of 5-hydroxytryptamine (5-HT) in the brain, suggest a cautious administration of the plant extract owing to its negative influence on female sexual behavior. PMID- 20359874 TI - Trypanocidal and antileukaemic effects of the essential oils of Hagenia abyssinica, Leonotis ocymifolia, Moringa stenopetala, and their main individual constituents. AB - Essential oils from three Ethiopian medicinal plants; Hagenia abyssinica (Rosaceae), Leonotis ocymifolia (Lamiaceae), and Moringa stenopetala (Moringaceae) were investigated for their chemical composition, trypanocidal, and cytotoxic activities. Twenty components were identified from the essential oil of H. abyssinica female flowers, ledol (58.57%) being the principal volatile oil component. Sixty-eight components were identified from the essential oil of L. ocymifolia aerial part, caryophyllene oxide (12.06%) being the major component. The essential oil of M. stenopetala seeds was dominated by isothiocyanates; benzyl isothiocyanate (54.30%) and isobutyl isothiocyanate (16.37%) were the major components. The trypanocidal (Trypanosoma b. brucei) and antileukaemic (HL 60) effects of the three essential oils were studied. The oil of M. stenopetala seeds and its main compound, benzyl isothiocyanate showed the most potent trypanocidal activities with IC(50) values of 5.03 MUg/ml and 1.20 MUg/ml, respectively. The oils of H. abyssinica and L. ocymifolia exhibited trypanocidal activities with IC(50) values of 42.30 MUg/ml and 15.41 MUg/ml, respectively. Individual components (28 compounds) of the essential oils bearing different functional groups were also studied for their structure-activity relationships using trypanosomes and human leukaemia cells. Cinnamaldehyde (IC(50)=2.93 MUg/ml) (a representative for aldehydes), nerolidol (IC(50)=15.78 MUg/ml) (an alcohol), cedrene (IC(50)=4.07 MUg/ml) (a hydrocarbon), benzyl isothiocyanate (IC(50)=1.20 MUg/ml) (a representative for mustard oils), 1,8-cineole (IC(50)=83.15 MUg/ml) (an ether), safrole (IC(50)=18.40 MUg/ml) (aromatics with allyl and/or methoxy side chains), carvone (IC(50)=12.94MUg/ml) (a ketone), styrene oxide (IC(50)=3.76 MUg/ml) (an epoxide) and carvacrol (IC(50)=11.25 MUg/ml) (a phenol) showed the most potent trypanocidal activities from their respective groups. Of all essential oil components tested, carvone (selectivity index (SI)=17.46) and styrene oxide (SI=19.92) showed good selective indices for the parasite with minimal toxicity on the human leukaemia cells. These compounds could therefore serve as lead structures for the development of trypanocidal agents with higher potency. PMID- 20359875 TI - Differential lymphocyte infiltration in small airways and lung parenchyma in COPD patients. AB - BACKGROUND: In COPD, although histological lesions at both the small airways (wall thickening and tissue remodeling) and lung parenchyma (emphysematous destruction) are definitely different, the inflammatory cells involved in both processes are the same. Our study aims to determine if these histopathological phenotypes are related to two different lymphocyte profiles. METHODS: Distribution and cell density of CD3(+), CD4(+), CD8(+) and B lymphocytes were compared in small airways and parenchymal interstitium of 9 non-smokers, 18 smokers without COPD, 16 smokers with moderate COPD and 16 patients with very severe COPD undergoing lung transplantation. Spatial distribution of lymphocytes in periemphysematous parenchyma was also assessed. RESULTS: CD3(+) and B cell densities were significantly higher in small airways than parenchyma interstitium of very severe COPD patients. Furthermore, CD8(+) cells were increased in the epithelium of airways of moderate COPD patients compared to non-smokers. Although CD8(+) cell density was increased in parenchyma of COPD patients, CD8(+) and B cell densities were similar when comparing periemphysematous and non emphysematous alveolar interstitium. CONCLUSIONS: In COPD, it is true that the small airways' wall shows a clear inflammatory pattern, with a high mononuclear infiltration and tissue remodeling. However, parenchymal interstitium shows a milder CD8(+) infiltration which, moreover, is not spatially related to emphysematous destroyed areas. PMID- 20359876 TI - Inositol phosphate synthesis and the nuclear processes they affect. AB - Recent studies have implicated inositol phosphates, a highly charged family of lipid-derived metabolites, in a slue of cellular processes. However, it is their involvement in nuclear events that has attracted much attention. Several IP molecules have been linked to gene regulatory factors, chromatin-remodeling complexes, mRNA export, and DNA repair machinery, yet in many instances direct mechanistic roles remain elusive. The purpose of this review is to cover the latest data gathered regarding only the nuclear roles of the various inositol phosphates while simultaneously providing a step-by-step tour of IP synthesis in eukaryotes. PMID- 20359877 TI - An external evaluation of a peer-run outreach-based syringe exchange in Vancouver, Canada. AB - OBJECTIVE: Vancouver, Canada has been the site of an epidemic of human immunodeficiency virus (HIV) amongst injection drug users (IDU). In response, the Vancouver Area Network of Drug Users (VANDU) initiated a peer-run outreach-based syringe exchange programme (SEP) called the Alley Patrol. We conducted an external evaluation of this programme, using data obtained from the Vancouver Injection Drug Users Study (VIDUS). METHODS: Using generalised estimating equations (GEE) we examined the prevalence and correlates of use of the SEP amongst VIDUS participants followed from 1 December 2000 to 30 November 2003. RESULTS: Of 854 IDU, 233 (27.3%) participants reported use of the SEP during the study period. In multivariate GEE analyses, service use was positively associated with living in unstable housing (adjusted odds ratio [AOR]=1.83, 95% confidence interval [CI]: 1.39-2.40), daily heroin injection (AOR=1.31, 95% CI: 1.01-1.70), daily cocaine injection (AOR=1.34, 95% CI: 1.03-1.73), injecting in public (AOR=3.07, 95% CI: 2.32-4.06), and negatively associated with needle reuse (AOR=0.65, 95% CI: 0.46-0.92). CONCLUSION: The VANDU Alley Patrol SEP succeeded in reaching a group of IDU at heightened risk for adverse health outcomes. Importantly, access to this service was associated with lower levels of needle reuse. This form of peer-based SEP may extend the reach of HIV prevention programmes by contacting IDU traditionally underserved by conventional syringe exchange programmes. PMID- 20359878 TI - Effect of different tannery sludge compost amendment rates on growth, biomass accumulation and yield responses of Capsicum plants. AB - Composting has been recognized as one of the most cost effective and environmentally sound alternatives for organic wastes recycling from long and composted wastes have a potential to substitute inorganic fertilizers. We investigated the potential of composted tannery sludge for ornamental purposes and to examine the effects of two different composts and concentrations on ornamental Capsicum growth. The two composts were produced with tannery sludge and the composition of each compost was: compost(1) of tannery sludge (C(1)TS) - tannery sludge+sugarcane straw and cattle manure mixed in the ratio 1:3:1 (v:v:v); compost(2) of tannery sludge (C(2)TS) - tannery sludge+"carnauba" straw and cattle manure in the ratio 1:3:1 (v:v:v). Each compost was amended with soil at rates (% v:v) of 0%, 25%, 50%, 75% and 100% (designation hereafter as T(1) T(5), respectively). The number of leaves and fruits were counted, and the stem length was also measured. Chlorophyll content was recorded on three leaves of each harvested plant prior to harvest. Number of leaves and fruits, stem length, dry weight of shoot and roots did not vary significantly between the plants grown in two tannery composts. All the treatments with composted tannery sludge application (T(2)-T(5)) significantly increased the number of leaves and fruits, stem length and chlorophyll content compared with the control (T(1)). The chlorophyll content was higher in plants growing in the C(1)TS compared to C(2)TS. The results of the present study further suggest that Capsicum may be a good option to be grown on composted tannery amended soil. PMID- 20359879 TI - Fines migration from soil daily covers in Hong Kong landfills. AB - Laboratory tests using 240 mm diameter columns were conducted to study fines migration in conditions that simulate daily soil covers in Hong Kong municipal solid waste landfills. Five factors suspected to affect fines migration were examined: moisture content at soil compaction, overburden pressure, pumping rate, cover thickness, and soil-waste interface condition. The results show that moisture content at compaction, cover thickness, and soil-waste interface are the most influential parameters on fines migration in completely decomposed granite daily covers. The measured equivalent sizes of migratory fines from the soil covers were in the range of 4-140 MUm. The majority of migratory fines migrated during first permeations, representing 64-86% of the total by mass. Larger particles tended to migrate from the soil mass during the saturation process. In a typical run, about 0.0018% of the total cover soil (by dry weight) was washed out during a typical 1h rainfall event. The results of the laboratory studies point to important engineering implications on the operation of local MSW landfills regarding the use of sandy daily covers. PMID- 20359880 TI - Ultra-low fouling and functionalizable zwitterionic coatings grafted onto SiO2 via a biomimetic adhesive group for sensing and detection in complex media. AB - Non-specific protein binding from human plasma and serum has severely hindered the full capabilities of biosensors concerned with cancer biomarker detection. Currently, there is a strong desire for developing new materials which allow for the convenient attachment of an ultra-low fouling and functionalizable surface coating which can be used for highly sensitive and label-free detection of target analytes directly from complex media. In this work, a short 20 min in situ "graft to" protocol using Tris pH 8.5 buffer was developed for zwitterionic carboxybetaine methacrylate (CBMA) polymer conjugates containing the adhesive biomimetic moiety, 3,4-dihydroxy-L-phenylalanine (DOPA), on SiO(2) substrates. Using a surface plasmon resonance (SPR) biosensor, different buffers, pH values, salt concentrations, and temperatures were investigated for determining the "graft to" conditions that yield dense polymer films which both minimize non specific protein adsorption and maximize antibody immobilization. The optimized surface coatings were shown to be highly protein resistant to 100% human blood plasma and serum. Subsequent antibody functionalized surfaces without any blocking agents enabled the specific detection of the cancer biomarker ALCAM directly from undiluted human serum down to 64 ng/mL. The successful use of this zwitterionic surface coating for detection from complex media on SiO(2) surfaces indicates its potential for broad impacts in the development of implantable medical devices, in vivo diagnostics, and nano-scale biosensors. PMID- 20359881 TI - Mirror foot and our surgical experience: a case report and literature review. AB - Preaxial mirror polydactyly of foot is a rare congenital anomaly with even fewer documentations for definitive treatment. To provide a sensate, near normal foot with ability to wear shoes is difficult to achieve in this variant with fibular dimelia and calcaneal duplication, with a delayed presentation at 6 years. Our case obtained satisfactory cosmetic and functional outcome upon excision of accessory calcaneum and the medial three toes along with covering the defect with local full thickness skin flap: a first of its kind mentioned in literature. We report this case because of its rarity and to share our surgical experience and its acceptable outcome. PMID- 20359882 TI - Epimutations and cancer predisposition: importance and mechanisms. AB - Germline sequence mutations in tumour suppressor genes can cause cancer predisposition syndromes. More recently, epimutations have also been proposed to cause at least one such syndrome, hereditary non-polyposis colorectal cancer (HNPCC). 'Epigenetic predisposition', is defined as an inherited propensity to an altered epigenetic state in normal tissues that confers a predisposition to disease. Genetic sequence variations acting in cis or trans may contribute to epigenetic variations. Understanding the origin of epimutations will inform cancer risk assessment and will also aid the design and application of new therapies that target the epigenome. PMID- 20359884 TI - Beta-band oscillations--signalling the status quo? AB - In this review, we consider the potential functional role of beta-band oscillations, which at present is not yet well understood. We discuss evidence from recent studies on top-down mechanisms involved in cognitive processing, on the motor system and on the pathophysiology of movement disorders that suggest a unifying hypothesis: beta-band activity seems related to the maintenance of the current sensorimotor or cognitive state. We hypothesize that beta oscillations and/or coupling in the beta-band are expressed more strongly if the maintenance of the status quo is intended or predicted, than if a change is expected. Moreover, we suggest that pathological enhancement of beta-band activity is likely to result in an abnormal persistence of the status quo and a deterioration of flexible behavioural and cognitive control. PMID- 20359883 TI - Exploring genetic susceptibility to cancer in diverse populations. AB - Incidence rates for many cancers differ markedly by race/ethnicity and furthering our understanding of the genetic and environmental causes of such disparities is a scientific and public health need. Genome-wide association studies (GWAS) are widely acknowledged to provide important information about the etiology of common cancers. To date, these studies have been primarily conducted in European-derived populations. There are important reasons for extending the reach of GWAS studies to other groups and for conducting multiethnic genetic studies involving multiple populations and admixed populations. These include a (1) need to discover the full scope of variants that affect risk of disease in all populations, (2) furthering the understanding of disease pathways, and (3) to assist in fine mapping of genetic associations by exploiting the differences in linkage disequilibrium between populations to narrow the range of marker alleles demarking regions that contain a true biologically relevant variant. Challenges to multiethnic studies relating to study power, control for hidden population structure, imputation, and use of shared controls for multiple cancer endpoints are discussed. PMID- 20359885 TI - Neural correlations, decisions, and actions. AB - Multielectrode recording experiments let us measure correlations between the activity of individual neurons and the neural circuits in which they are embedded. Recently, multielectrode studies have been emphasizing how correlated neuronal activity is linked with behavior. Decisions are fundamental to voluntary behavior. Here, we discuss computations necessary to turn a decision into an action and review progress in studying correlated neural activity in areas of the brain which link sensory and motor representations. The themes that emerge are that correlated patterns of activity in populations of neurons can be revealed by measurements of field potential fluctuations and that these measurements can relate the activity of individual neurons to the activity of populations of neurons distributed across different regions of the brain. Investigations into patterns of neuronal correlation are helping us to understand how decisions and other cognitive processes result from the interactions between different brain systems that are responsible for controlling and regulating our behavior. PMID- 20359886 TI - Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer. AB - BACKGROUND: The 70-gene signature (MammaPrint) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer. In order to decide upon its use, a systematic comparative analysis of the effects of the 70-gene signature, the Sankt Gallen guidelines and the Adjuvant Online Software for these patients on survival, quality of life and costs is warranted. METHODS: A Markov decision model was used to simulate the 20-year costs and outcomes (survival and quality-of-life adjusted survival (QALYs)) in a hypothetical cohort of node-negative, estrogen receptor positive breast cancer patients. Sensitivity and specificity of the three prognostic tools were based on 5 and 10 years breast cancer specific survival and distant metastasis as first event, derived from a pooled analysis consisting of 305 tumour samples from 3 previously reported validation studies concerning the 70-gene signature. RESULTS: Small differences in survival, but substantial differences in quality-adjusted survival between the prognostic tools were observed. Quality-adjusted survival was highest when using the 70-gene signature. Based on costs per QALY, the 70 gene has the highest probability of being cost-effective for a willingness to pay for a QALY higher than euro12.000. Sankt Gallen showed the highest survival rates compared to the 70-gene signature, but leads to a substantial larger amount of adjuvant chemotherapy and lower cost-effectiveness, thus demanding a high willingness to pay to save a life year. CONCLUSIONS: When deciding upon the cost effectiveness of the prognostic tests, the 70-gene signature improves quality adjusted survival and has the highest probability of being cost-effective. PMID- 20359887 TI - Efficient strategy for enhancing aspergiolide A production by citrate feedings and its effects on sexual development and growth of marine-derived fungus Aspergillus glaucus. AB - Aspergiolide A production enhancement by citrate and its effects on growth and sexual development of marine-derived fungus Aspergillus glaucus HB1-19 were investigated. In agar plate culture, 15 mM citric acid decreased colony radial growth and aspergiolide A production by 31.5% and 23.0%, respectively. It also improved sexual cleistothecium formation by 360% but depressed asexual conidiospore generation by 84.8%. In submerged culture, adding 40 mM citric acid finally promoted aspergiolide A production by 80.0%, which accompanied with 16.7% increase of biomass and 10.0% enhancement of sugar utilization. Differently, sodium citrate made no obvious or even opposite effects. Citrate and low pH could significantly improve pyruvate accumulation but inhibit succinate and fumarate production. Moreover, low pH was favorable to citrate utilization. Organic acids changes were closely related to aspergiolide A biosynthesis. Comparing to pH controls, effects of citric acid comprised pH decrease solicitation and citrate utilization enhancement. PMID- 20359888 TI - Chemical looping reforming of waste cooking oil in packed bed reactor. AB - Chemical looping steam reforming for hydrogen production from waste cooking oil was investigated using a packed bed reactor. The steam to carbon ratio of 4 and temperatures between 600 and 700 degrees C yielded the best results of the range of conditions tested. Six cycles at two weighted hourly space velocities (WHSV of 2.64 and 5.28 h(-1)) yielded high (>0.74) and low (<0.2) oil conversion fractions, respectively, representing low and high coking conditions. The WHSV of 2.64 h(-1) yielded product concentrations closest to equilibrium values calculated assuming a fresh rapeseed oil composition. Repeated cycling revealed some output oscillations in reactant conversion and in the extent of Ni-NiO conversion, but did not exhibit deterioration by the 6th cycle. The selectivity of CO, CO(2) and CH(4) were remarkably constant over the performed cycles, resulting in a repeatable syngas composition with H(2) selectivity very close to the optimum. PMID- 20359889 TI - Design and an efficient synthesis of new thiorotenone derivatives. AB - A series of novel 4-aryl-thiopyrano[3,4-b]pyran-5-one derivatives were synthesized through an efficient one-pot three-component reaction under solvent free conditions. This work provides a new series of derivatives of thiorotenone with potential biological activity for biomedical screening. PMID- 20359890 TI - Structural requirement(s) of N-phenylthioureas and benzaldehyde thiosemicarbazones as inhibitors of melanogenesis in melanoma B 16 cells. AB - In order to define the structural requirements of phenylthiourea (PTU), a series of thiourea and thiosemicarbazone analogs were prepared and evaluated as inhibitors of melanogenesis in melanoma B16 cells. The most potent analog was 2 (4-tert-butylbenzylidene)hydrazinecarbothioamide (1u) with an IC(50) value of 2.7 microM in inhibition of melanogenesis. The structure for potent inhibitory activity of these derivatives are required with the direct connection of pi planar structure to thiourea without steric hinderance in PTU derivatives and the hydrophobic substituent at para position in case of semicarbazones. PMID- 20359892 TI - Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells. AB - Correct spatio-temporal regulation of Wnt5a signaling is required for normal developmental morphogenesis, and defects in this pathway are linked to tumorigenesis. The precise role of Wnt5a signaling in cancer has, however, been a matter of controversy. Loss of Wnt5a signaling is related to development of lymphoid malignancies, whereas constitutively active Wnt5a signaling is involved in invasion or metastasis of several cancers. Interestingly, recent studies in Drosophila and mouse have revealed that disrupted cell polarity might contribute to invasion/metastasis of cancers. Wnt5a activates the planar cell polarity (PCP) pathway, partly through the receptor tyrosine kinase Ror2. Here, we review developments in our understanding of the molecular mechanisms underlying Wnt5a signaling, with an emphasis on the role of Ror2 in cancer. We also propose a model where the outcomes of normal and aberrant Wnt5a/Ror2 signaling depend on cell/tissue-tropic contexts. PMID- 20359891 TI - A prodrug approach towards the development of tricyclic-based FBPase inhibitors. AB - For the purpose of reducing the strong CYP3A4 inhibitory potency of diamide prodrug 4, cyclic prodrugs of tricyclic-based FBPase inhibitors were synthesized. Extensive SAR studies led to the discovery of pyridine-containing cyclic prodrug 20, which strongly inhibited glucose production in monkey hepatocytes and also showed weak CYP3A4 inhibitory potency. PMID- 20359893 TI - Antibodies and immune effectors: shaping Gram-negative bacterial phenotypes. AB - Antibodies and immune effectors (IE) are crucial for protecting humans from Gram negative bacteria. Antibodies can bind outer membrane or cell surface (e.g. flagella) structures, thereby preventing adhesion, disrupting specific virulence functions, or targeting bacteria for phagocytosis. IE (antimicrobial peptides, cytokines and hormones) impinge on bacterial infections and regulate immune responses. A developing paradigm is that bacteria 'recognize' antibodies and IE, which alert them to challenging environments, promoting resistance phenotypes and increased virulence. A broader understanding of the interactions between bacteria and antibodies and IE will help define their relative contributions to pathogenesis, and perhaps indicate how we could use antibodies and IE to shape bacterial phenotypes that are easier for the immune system to control. PMID- 20359894 TI - A neuropathological study at autopsy of early onset spinocerebellar ataxia 6. AB - Spinocerebellar ataxia type 6 (SCA6) is a late-onset, autosomal dominantly inherited ataxic disorder, and most previous clinical studies consider SCA6 to be a "pure" cerebellar ataxia. We carried out a detailed pathoanatomical study at autopsy of two patients, brother and sister, with genetically confirmed SCA6. The disease in both patients was early onset and short, which is atypical for SCA6. We observed severe neurodegeneration in the cerebellum, dentate nucleus and olivary nuclei. Both patients showed evidence of synaptic modification in the cerebellar cortex, which morphologically confirmed the existence of retrograde and anterograde trans-synaptic degeneration secondary to the cerebellar cortical lesion. Furthermore, our study shows for the first time that neurodegeneration in SCA6 occurs in the spinal cord. Finally, our postmortem study confirms that SCA6 is not a simple "pure" cerebellar disease, but a complex neurodegenerative condition in which many extracerebellar structures are involved. PMID- 20359895 TI - A healthy man with intractable hiccups. AB - We present a patient with intractable hiccups. Medical treatment decreased the frequency of the hiccups to only 5-10 per minute. After exclusion of gastrointestinal reasons for the hiccups, cranial MRI revealed a small lesion in the right rhomboid fossa, close to the vagal trigone. Microsurgical resection of the lesion was performed via a suboccipital median craniotomy. The histopathological diagnosis was a cavernoma. Promptly after surgery the patient was free of symptoms. Intractable hiccups can be associated with intracranial pathologies, including lesions in the brain stem, which we highlight with the presentation of this patient. PMID- 20359896 TI - Solitary spinal metastasis of Hurthle cell thyroid carcinoma. AB - Hurthle cell carcinoma is a rare variant of differentiated thyroid cancer that occasionally forms distant metastases. However, even in the presence of metastases, patients with Hurthle cell carcinoma have a relatively good prognosis. There are few reports of Hurthle cell carcinoma metastases to the vertebral column, and none describing aggressive resection of spinal metastases. Here, we report a 68-year-old woman with a solitary metastasis of Hurthle cell carcinoma to the T1 vertebral body causing severe kyphotic deformity, myelopathy, and pain. The patient was treated with aggressive excisional decompression of the spinal cord and T1 vertebral body resection from an entirely posterior approach. Reconstruction and stabilization of the anterior spine was accomplished with a transforaminal lumbar interbody fusion allograft spacer and posterior instrumentation. We discuss aspects of the diagnosis, management, patient selection, and surgical treatment of metastatic Hurthle cell carcinoma in reference to the literature. PMID- 20359897 TI - Efficacy and reliability of highly functional open source DICOM software (OsiriX) in spine surgery. AB - We evaluated the feasibility and reliability of open source Digital Imaging and COmmunication in Medicine (DICOM) imaging software, OsiriX (Antoine Rosset, 2003 2009), in spine surgery. CT data were used and processed with OsiriX and with commercial software for comparison. Images were reconstructed and compared in volume rendering (VR) and multi-planar reconstruction (MPR) mode. When all images were compared, the three-dimensional (3D) reconstructed images from both software packages showed considerable consistency in VR mode. Measurements in MPR mode also showed similar values with no statistically significant difference. These results demonstrate that OsiriX has approximately equivalent values to commercial software and provides reliable preoperative 3D information for the surgical field. In addition, any clinician, can obtain information using OsiriX at any time. Thus, OsiriX is a helpful tool in preoperative planning for spine surgery. PMID- 20359898 TI - Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2 phenylbenzimidazole derivatives. AB - Seventy-six 2-phenylbenzimidazole derivatives were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, BVDV, Sb-1, HSV-1, and YFV, while HIV-1 and VSV were not affected, and RSV, VV and Reo-1 were only susceptible to a few compounds. Thirty-nine compounds exhibited high activity (EC(50)=0.1-10microM) against at least one virus, and four of them were outstanding for their high and selective activity against VV (24, EC(50)=0.1microM) and BVDV (50, 51, and 53 with EC(50)=1.5, 0.8, and 1.0microM, respectively). The last compounds inhibited at low micromolar concentrations the NS5B RdRp of BVDV and also of HCV, the latter sharing structural similarity with the former. The considered compounds represent attractive leads for the development of antiviral agents against poxviruses, pestiviruses and even HCV, which are important human and veterinary pathogens. PMID- 20359899 TI - The midgut of Cephalotes ants (Formicidae: Myrmicinae): ultrastructure of the epithelium and symbiotic bacteria. AB - The ultrastructural analysis of the midgut of Cephalotes atratus, C. clypeatus, and C. pusillus reveled that the midgut epithelium lays on a basal lamina and is composed basically of three cell types: digestive cells, regenerative cells, and goblet cells. In these ants, the rough endoplasmic reticulum, in addition to producing digestive enzymes, is involved in the formation of concretions and ion storage in specialized vacuoles present in the midgut. These concretions are spherocrystals and may contribute to stabilize the pH and to maintain symbiotic bacteria found between microvilli. The ultrastructure analysis of these bacteria revealed the presence of a double envelope typical of gram-negative bacteria. For the three species examined, the ultrastructure similarities are conspicuous, suggesting that this may be the pattern for the genus Cephalotes. Details of the relationship between bacteria and microvilli were examined. PMID- 20359900 TI - Characterization of radioactive particles using non-destructive alpha spectrometry. AB - Spherical particles with known properties were used to demonstrate and test a novel software package known as AASIFIT, which is able to unfold complex alpha spectra. A unique feature of the program is that it uses simulated peak shapes in the fitting process. The experimental reference particles in the testing were artificially produced U particles of diameter 1.4microm and a nuclear bomb particle with a twenty-fold greater diameter, mainly composed of U and Pu dioxides. AASIFIT was used to determine the density of the U particles. In addition, the activities of (239+240)Pu and (241)Am were determined for the nuclear bomb particle and compared to earlier determinations in the literature. The results of this investigation demonstrated that the software can be used to estimate the properties of particles emitting alpha radiation. However, the composition and geometry of the investigated particles need to be known with good accuracy for reliable estimates. Furthermore, uncertainties in the stopping power data, especially for U and Pu, may have an influence on the results obtained from the software. PMID- 20359901 TI - Preparation of (111)In-DTPA morpholino oligomer for low abdominal accumulation. AB - An ability to quantitate the beta cell mass by noninvasive nuclear imaging will be very useful in the prevention, diagnosis, and treatment of diabetes. However, to be successful, radioactivity from the pancreas must not be obscured by the background radioactivity in the abdomen. Pretargeting offers the promise of achieving high target organ to normal tissue ratios. In preparation for pancreas imaging studies by pretargeting using morpholino oligomers (MORF/cMORF), it was necessary to develop a simple and efficient method to radiolabel the cMORF effector. Because we have shown that labeling the cMORF with (111)In via DTPA reduces excretion into the intestines compared to labeling with (99m)Tc via MAG(3), the conjugation of DTPA to cMORF was investigated for (111)In labeling. The amine-derivatized cMORF was conjugated with DTPA using 1-ethyl-3(3 dimethylaminopropyl)carbodiimide hydrochloride (EDC) as an alternative to the conventional cyclic anhydride. The conjugation efficiency (represented by the number of DTPA groups attached per cMORF) was investigated by changing the EDC, DTPA, and cMORF molar ratios. Different open columns were considered for the purification of DTPA-cMORF. Before conjugation, each cMORF molecule was confirmed to have an amine by trinitrobenzene sulfonic acid (TNBS) assay using the omega amino butyric acid as positive standard and the non-amine derivatized cMORF as negative standard. The average number of DTPA groups per cMORF was 0.15-0.20 following the conjugation over a cMORF/DTPA molar ratio of 0.5-5 and over a cMORF/EDC molar ratio of 20-60. The conjugation efficiency was lower than expected probably due to steric hindrance. A 1 x 50cm P-4 column using ammonium acetate as eluting buffer provided an adequate separation of DTPA-cMORF from free DTPA. The (111)In labeling efficiency by transchelation from acetate exceeded 95%, thus avoiding the need for postlabeling purification. Despite the lower than expected conjugation efficiency in which no more than one-fifth of the cMORF were DTPA-derivatized, a specific radioactivity of at least 300microCi/microg or 1.90Ci/micromol of cMORF was achieved. In conclusion, a protocol is described for (111)In-DTPA-cMORF that provides the high specific activity favorable to beta cell imaging because of the low mass fraction of beta cells in pancreas (1-2%) and obviates the need for postlabeling purification. PMID- 20359902 TI - Polyamine biosynthesis and control of the development of functional pollen in kiwifruit. AB - The role of polyamines (PAs) in plant reproduction, especially pollen development and germination has been demonstrated in several higher plants. The aim of the present research was to investigate PA involvement in pollen development and germination in dioecious kiwifruit (Actinidia deliciosa). Differences in PA content, level and gene expression for PA biosynthetic enzymes, and the effect of PA biosynthetic inhibitors were found during pollen development (or abortion in female flowers). Whereas PAs, especially spermidine (Spd), remained high throughout the development of functional pollen, the levels collapsed by the last stage of development of sterile pollen. Mature and functional pollen from male fertile anthers showed S-adenosyl methionine decarboxylase activity (SAMDC; involved in Spd biosynthesis) throughout microgametogenesis, with high levels of soluble SAMDC found starting from the late uninucleate microspore stage. Soluble SAMDC was absent in male-sterile anthers. Arginine decarboxylase [ADC; for putrescine (Put) biosynthesis] showed little difference in functional vs sterile pollen; ornithine decarboxylase [ODC; also for putrescine (Put) biosynthesis] was present only in sterile pollen. Ultrastructural studies of aborted pollen grains in male-sterile flowers showed that cytoplasmic residues near the intine contain vesicles, extruding towards the pollen wall. Very high SAMDC activity was found in the wall residues of the aborted pollen. The combined application in planta of competitive inhibitors of S-adenosylmethionine decarboxylase (MGBG) and of spermidine synthase (CHA), or of D-arginine (inhibitor of Put synthesis), to male fertile plants led to abnormal pollen grains with reduced viability. The importance of PAs during male-fertile pollen germination was also found. In fact, PA biosynthetic enzymes (ADC and, mainly, SAMDC) were active early during pollen hydration and germination in vitro. Two different SAMDC gene transcripts were expressed in germinating pollen together with a lower level of ADC transcript. Gene expression preceded PA enzyme activity. The application of PA inhibitors in planta drastically reduced pollen germination. Thus, low free Spd can lead either to degeneration or loss of functionality of kiwifruit pollen grains. PMID- 20359903 TI - Aspirin and non-small cell lung cancer resections: effect on long-term survival. AB - OBJECTIVE: Survival after resections for non-small cell lung cancer remains poor. Recurrent lung cancer remains common. Due to the common risk factor of smoking, cardiovascular deaths occur in the absence of recurrent lung cancer in up to 15% of patients. Aspirin has been proven to reduce cardiovascular mortality as a secondary prophylactic agent, but not as a primary agent. Aspirin being a COX-2 inhibitor has been shown to reduce the chance of metastasis in adenocarcinoma but not squamous carcinoma. We sought to investigate the effect of long-term aspirin therapy on survival post potentially curative surgery. METHODS: We analysed a prospective thoracic surgical database, from time period 2003 to date. Patients who were on aspirin pre-operatively, N=412 were compared to non users, N=1353. Patient long-term outcome was assessed utilising the national strategic tracking service that operates in the United Kingdom. Cox proportional hazards analysis was used to determine significant factors affecting survival. RESULTS: 100% survival follow up was achieved. Regular users of aspirin had >5% increased survival, which was significant, p=0.05, despite having a higher cardiovascular risk profile. Mode of death data was not available. CONCLUSIONS: Adjuvant aspirin post resection for potentially curative non-small cell lung cancer significantly increases survival. The mechanism of increased survival needs further investigation and is the basis for the trial: Adjuvant Aspirin for Non-Small cell Lung Cancer--The Big A Trial. www.TheBigATrial.co.uk. PMID- 20359904 TI - The Ross operation - a feasible and safe option in the setting of a bicuspid aortic valve? AB - OBJECTIVES: The Ross operation in the setting of a bicuspid aortic valve (BAV) remains controversial. Using data from the German Ross Registry, we sought to investigate the effect of the presence of a BAV on autograft function and diameters over time after the Ross operation compared with the presence of a tricuspid aortic valve (TAV). METHODS: A total of 1277 patients (mean age 42.2 + or - 15.3 years) with intra-operatively documented aortic valve morphology during the Ross operation were analysed in the present study (sub-coronary technique, n=648, root replacement technique, n=629 patients). A BAV was present in 70.9% of patients. Clinical and echocardiographic follow-up was performed preoperatively and at pre-specified intervals (mean follow-up 5.7 + or - 3.8 years, 6806 patient years). Hierarchical multilevel modelling techniques were used for the statistical analysis of serial measurements and comparisons among groups. RESULTS: Initial neo-aortic regurgitation was lower in the BAV group (0.52 vs 0.62 aortic insufficiency (AI) grades, p=0.008), whereas the annual increase of it did not differ among groups. In both surgical techniques, no significant development of neo-aortic regurgitation (<0.02 AI grades per year) could be detected. Initial aortic annulus and sinus dimensions did not differ in the presence of a BAV. However, BAV patients developed a higher degree of annulus and sinus dilatation over time (0.20mm per year vs 0.06 mm per year, p=0.003; 0.24 vs 0.11 mm per year, p=0.013). This effect persisted when allowing for the two different surgical techniques. Baseline sinotubular junction (STJ) diameters did not differ among groups and annual increase thereof was similar (29.15 mm vs 28.9 mm, p=0.69; 0.44 mm vs 0.35 mm, p=0.15). CONCLUSIONS: For the observed time period, postoperative neo-aortic regurgitation after the Ross procedure did not differ between patients with a BAV or a TAV. Root dimensions, although clinically not relevant, increased in both valve entities supporting surgical reinforcement strategies. We cannot consider a BAV as a contraindication for the Ross operation. PMID- 20359905 TI - Is NT-pro-BNP predictive of atrial fibrillation in patients undergoing coronary artery bypass surgery? PMID- 20359906 TI - Long-term results of hybrid endovascular repair for thoraco-abdominal aortic aneurysms. AB - OBJECTIVE: The treatment of thoraco-abdominal aortic aneurysms (TAAAs) is extremely laborious, due to the surgical complexity of this condition. In particular, postoperative spinal paraplegia poses a severe complication that significantly lowers patient's quality of life. In 1997, we devised a hybrid procedure consisting of extended endovascular aortic repair (EVAR) and visceral reconstruction. In this article, we report the long-term results obtained from this procedure. METHODS: We conducted 1106 endovascular aortic repairs between 1997 and 2008. Among these, we selected 86 cases of TAAA. The mean patient age was 71.6 years. Preoperative complications included 19 cases of stroke, 22 cases of coronary artery disease (CAD) and 16 cases of chronic obstructive pulmonary disease (COPD). Cerebrospinal fluid drainage was initiated during the operation. We performed bypasses from the aortic bifurcation to abdominal visceral arteries, and deployed stent grafts to exclude the entire TAAA. RESULTS: Operative time averaged 386 min. We lost two patients and encountered only one case of graft occlusion. Two patients had acute renal failure, but neither required a tracheostomy. Furthermore, no patients exhibited paraplegia or delayed paraplegia. We observed endoleaks in nine cases, and shrunken aneurysms in 73 cases. Long-term results included survival rates of 94.8%, 85.8%, 80.2% and 66.6% at 2, 5, 8 and 10 years, respectively. Only two patients died from aortic events. Rates of freedom from aortic events were 90.7%, 80.6%, 70.8% and 70.8% at 2, 5, 8 and 10 years, respectively. CONCLUSIONS: The hybrid TAAA-repair protocol yielded satisfactory results. Although thorough follow-up is required for visceral bypass, this procedure could become the standard for TAAAs. PMID- 20359907 TI - Where the sun does not shine: is sunshine protective against melanoma of the vulva? AB - Intermittent sun exposure and sunburn are strong predictors of cutaneous malignant melanoma (CMM). On the other hand, melanomas may arise also in non-sun exposed areas such as the vulva. However, little is known about a possible relationship between sun exposure and vulvar melanoma. Temporal and latitudinal dependencies of the incidence rates of vulvar melanoma were studied in comparison with those of CMM among Caucasians in Sweden, East Germany, USA and Victoria (Australia). The ratios of vulvar melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. The incidence rates of CMM have increased with time until recently, while those of vulvar melanoma have either decreased or remain constant. In USA vulvar melanoma incidence rates seem to increase from south to north, while for CMM incidence rates on sun exposed skin areas decrease from south to north. Comparison of latitudinal trends of the incidence rates of vulvar melanomas and CMM show opposite trends. Whenever CMM rates increase, either with time or with decreasing latitude (indicating increased sun exposure) the ratio of vulvar melanoma rates to CMM rates on exposed skin, seem to decrease. Thus, latitudinal trends seem to support the assumption that vulvar melanomas are not generated by UV radiation, and the possibility exists that solar UV radiation, probably via its role in vitamin D photosynthesis in exposed skin, may have a protective effect against vulvar melanoma and should be further investigated. PMID- 20359908 TI - 'Giving and taking': endothelial and beta-cells in the islets of Langerhans. AB - The beta-cells of the islets of Langerhans are embedded in a dense capillary network. The blood vessels supply the islet cells with nutrients and oxygen, and in turn take up the secreted islet hormones to deliver them to target tissues. In addition, vessels provide a basement membrane, which optimizes islet function. In this review we focus on the dynamic interactions between blood vessels and beta cells, which are pivotal for enhancing insulin expression and beta-cell proliferation in response to increased insulin demand during body growth, pregnancy, and virtually all conditions associated with insulin resistance. Importantly, a failure in this adaptive response might contribute to the onset of type 2 diabetes mellitus. PMID- 20359909 TI - Undifferentiated primate spermatogonia and their endocrine control. AB - The biology of spermatogonial stem cells is currently an area of intensive research and contemporary studies in primates are emerging. Quantitative regulation of sperm output by the primate testis seems to be exerted primarily on the transition from undifferentiated to differentiating spermatogonia. This review examines recent advances in our understanding of the mechanisms governing spermatogonial renewal and early differentiation in male primates, with a focus on the monkey. Emerging revisions to the classic view of dark and pale type A spermatogonia as reserve and renewing spermatogonial stem cells, respectively, are critically evaluated and essential features of endocrine control of undifferentiated spermatogonia throughout postnatal primate development are discussed. Obstacles in gaining a more complete understanding of primate spermatogonia are also identified. PMID- 20359910 TI - The application of ICH S6 to the preclinical safety evaluation of plasma derivative therapeutic products. AB - The ICH S6 guidance was developed to describe a rational science-based flexible approach to the preclinical evaluation for biotechnology-derived pharmaceutical products. It also suggested that some of the principles described may be suitable for plasma-derived therapeutics. Some of the specific concerns unique to protein based therapeutics include complexity in structure and potential immunogenicity. S6 has been interpreted by some industry and regulatory authorities, often due to lack of experience with these types of products, as encouraging a broader or more conventional toxicology program similar to that normally conducted for small molecules. The guidance does encourage important and necessary preclinical evaluations but also recognizes the limitations of studies in non-relevant animal species because they are without pharmacological interaction with the biologic. In addition, studies of human proteins are often limited in useful chronic, reproductive and carcinogenic toxicity evaluations by the immunological response in animals. Thus the safety evaluation of biopharmaceuticals and plasma derivatives in animals has limitations that cannot be adequately addressed by the use of testing paradigms used for small molecule pharmaceuticals. S6 focuses evaluations on well-designed studies in relevant species for reasonable time periods to make the best use of available resources and enable clinical trials. PMID- 20359911 TI - The Irish epilepsy surgery experience: Long-term follow-up. AB - AIM: To assess the long-term seizure outcome of Irish patients who underwent resective surgery for refractory epilepsy since 1975. We also wished to determine the impact of pathology and surgical technique (with particular reference to neocorticectomy) on seizure outcome. METHODS: A retrospective review of medical notes, radiological and histopathological records, was undertaken between 1975 and 2005. Missing data was supplemented by telephone calls to patients. One hundred and ninety-nine patients suited the criteria for inclusion and had at least 1-year follow-up (1-24 years, mean 7.0 years). Engel's criteria were used to classify seizure outcome at 1, 2, 5, 10, 15 and >15 years follow-up. RESULTS: The percentage of patients seizure free at 2, 5, 10, 15 and >15 years were, 56.6%, 41.4%, 44%, 25% and 31.3%, respectively. Of patients with a pathologically confirmed diagnosis of mesial temporal sclerosis, 55.6% were seizure free at 10 years. Equivalent figures for tumour were 62.5%, for cortical dysplasia, 34.8%, for those without any demonstrable pathologic abnormality, 50%, for dual pathology, 50% and for all others, 33.3%. Of those with 10 years or greater follow-up only 20% of neocorticectomy patients were in Engel class 1, compared with an average of 58.5% for the other surgical techniques. CONCLUSION: Seizure freedom rates for Irish Patients were comparable to other large retrospective studies. Patients who underwent selective procedures tended to do better than those undergoing lobar resections, in keeping with international trends. The surgical technique unique to the Irish cohort, temporal necocorticectomy, had the worst long-term outcome. PMID- 20359912 TI - What is the place of surgery for intermittent claudication? PMID- 20359914 TI - Early results after treatment of open abdomen after aortic surgery with mesh traction and vacuum-assisted wound closure. AB - OBJECTIVES: This study aimed to describe the use of vacuum-assisted wound closure (VAWC) and mesh traction to repair an open abdomen after aortic surgery. DESIGN: Prospective clinical study. MATERIAL AND METHODS: From October 2006 to April 2009, nine consecutive patients were treated; seven of the patients received laparostomy following abdominal compartment syndrome (ACS), while two wounds were left open initially. The indication for laparostomy was intra-abdominal pressure (IAP) > 20 mmHg or abdominal perfusion pressure (APP) < 60 mmHg and development of organ failure. V.A.C. therapy (KCI, San Antonio, TX, USA) was initiated with the laparostomy, and supplemented with a fascial mesh after 2 days. The wound was then closed stepwise with mesh traction and VAWC. RESULTS: All wounds could be closed following a median interval of 10.5 (range: 6-19) days after laparostomy. A median of four (range: 2-7) dressing changes were performed. One patient died on the seventh postoperative day. Two other patients died 38 and 50 days after final closure, respectively. Left colonic necrosis was seen in two patients while incisional hernia was observed in two patients. Mean follow-up duration was 17 (range: 2-36) months. CONCLUSION: VAWC with mesh traction was successful in terms of early delayed primary closure and is a useful tool in the treatment of open abdomen after aortic surgery. PMID- 20359915 TI - Proximal radial artery ligation (PRAL) for reduction of flow in autogenous radial cephalic accesses for haemodialysis. AB - OBJECTIVE: Juxta-anastomosis proximal radial artery ligation (PRAL) is a new surgical technique for reduction of excessive blood flow of radial cephalic fistulas (RCFs). PATIENTS AND METHODS: This prospective study included 37 consecutive patients (eight children and 29 adults) who underwent PRAL of high flow RCFs causing ischaemia (n = 2), aneurysmal degeneration of the vein (n = 14), and cardiac insufficiency (n = 7) or for prevention of cardiac overload (n = 14). Mean fistula age was 2.6 years for children and 7.4 years for adults. None had diabetes. Anatomical prerequisites (side-to-end anastomosis fistula and retrograde flow in the distal radial artery) were checked by ultrasound or angiography. Division and ligation of the juxta-anastomosis proximal radial artery were performed under regional anaesthesia. Patency following ligation was estimated according to the life table method. RESULTS: The success rate was 92% (34/37). The three failures included one excessive and two insufficient reductions of flow (<33%). Mean flow reduction rates were 50% in children and 53% in adults. Primary patency rates at 1 and 2 years were 88% +/- 6% and 74% +/- 9%, respectively. Secondary patency rates were 88% +/- 6% and 78% +/- 8%, respectively. CONCLUSION: PRAL is a simple, safe, and effective technique for reduction of flow in RCFs. PMID- 20359916 TI - Societal costs of insomnia. AB - Insomnia is the most common sleeping disorder and has been recognized as a major public health issue, associated with a high societal cost. The aim of this review is firstly to understand how the socio-demographic and career characteristics of insomniacs may influence the economical consequences of this disease. Secondly, it also tries to explain how patients seek help to cope with their insomnia. The review aims to carefully describe the possible links between insomnia and public health concerns as to point out what are the certitudes and the missing data on the consequences of insomnia on work, economics, accidents, costs and health related quality of life (HrQol). PMID- 20359917 TI - Pharmacokinetic and milk penetration of a difloxacin long-acting poloxamer gel formulation with carboxy-methylcellulose in lactating goats. AB - The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n=6) after subcutaneous administration of a long-acting poloxamer 407 gel formulation with carboxy-methylcellulose (P407-CMC). Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by non compartmental kinetic methods. Plasma and milk elimination half-lives after P407 CMC dosing were 35.19 h and 33.93 h, respectively. With this formulation, difloxacin achieved maximum plasma concentrations of 2.67+/-0.34 mg/L at 2.92+/ 1.20 h and maximum milk concentrations of 2.31+/-0.35 mg/L at 4.00+/-0.00 h. The area under the curve (AUC) ratio AUC(milk)/AUC(plasma) was 0.89 after P407-CMC administration. It was concluded that a 15 mg/kg dose of difloxacin within P407 CMC would be effective against mastitis pathogens with a minimum inhibitory concentration (MIC)<=0.12 mg/L. PMID- 20359918 TI - On the practical aspects of recording wideline QCPMG NMR spectra. AB - The practical aspects of applying CPMG for acquisition of wideline powder patterns are examined. It is shown that most distortions/modulations of spikelet spectra can be traced to the incoherent signal averaging from multiple coherence transfer pathways. A strategy for minimizing these distortions/modulations is described. Also, a few interesting observations regarding the implementation of the wideline WURST-QCPMG experiment are presented, namely the accumulation of second-order signal phase and the effects of varying the sweep rate and rf field of chirp pulses. PMID- 20359919 TI - Ceramic cells for high pressure NMR spectroscopy of proteins. AB - Application of high pressure to biological macromolecules can be used to find new structural states with a smaller specific volume of the system. High pressure NMR spectroscopy is a most promising analytical tool for the study of these states at atomic resolution. High pressure quartz cells are difficult to handle, high quality sapphire high pressure cells are difficult to obtain commercially. In this work, we describe the use of high pressure ceramic cells produced from yttrium stabilized ZrO(2) that are capable of resisting pressures up to 200 MPa. Since the new cells should also be usable in the easily damageable cryoprobes a completely new autoclave for these cells has been constructed, including an improved method for pressure transmission, an integrated safety jacket, a displacement body, and a fast self-closing emergency valve. PMID- 20359920 TI - Next generation sequencing in research and diagnostics of ocular birth defects. AB - Sequence capture enrichment (SCE) strategies and massively parallel next generation sequencing (NGS) are expected to increase the rate of gene discovery for genetically heterogeneous hereditary diseases, but at present, there are very few examples of successful application of these technologic advances in translational research and clinical testing. Our study assessed whether array based target enrichment followed by re-sequencing on the Roche Genome Sequencer FLX (GS FLX) system could be used for novel mutation identification in more than 1000 exons representing 100 candidate genes for ocular birth defects, and as a control, whether these methods could detect two known mutations in the PAX2 gene. We assayed two samples with heterozygous sequence changes in PAX2 that were previously identified by conventional Sanger sequencing. These changes were a c.527G>C (S176T) substitution and a single basepair deletion c.77delG. The nucleotide substitution c.527G>C was easily identified by NGS. A deletion of one base in a long polyG stretch (c.77delG) was not registered initially by the GS Reference Mapper, but was detected in repeated analysis using two different software packages. Different approaches were evaluated for distinguishing false positives (sequencing errors) and benign polymorphisms from potentially pathogenic sequence changes that require further follow-up. Although improvements will be necessary in accuracy, speed, ease of data analysis and cost, our study confirms that NGS can be used in research and diagnostic settings to screen for mutations in hundreds of loci in genetically heterogeneous human diseases. PMID- 20359921 TI - Current molecular diagnostic algorithm for mitochondrial disorders. AB - Mitochondrial respiratory chain disorders (RCD) are a group of genetically and clinically heterogeneous diseases, due in part to the biochemical complexity of mitochondrial respiration and the fact that two genomes, one mitochondrial and one nuclear, encode the components of the respiratory chain. Because of the large number of genes involved, attempts to classify mitochondrial RCD incorporate clinical, biochemical, and histological criteria, in addition to DNA-based molecular diagnostic testing. While molecular testing is widely viewed as definitive, confirmation of the diagnosis by molecular methods often remains a challenge because of the large number of genes, the two genome complexity and the varying proportions of pathogenic mitochondrial DNA (mtDNA) molecules in a patient, a concept termed heteroplasmy. The selection of genes to be analyzed depends on the family history and clinical, biochemical, histopathological, and imaging results, as well as the availability of different tissues for analysis. Screening of common point mutations and large deletions in mtDNA is typically the first step. In cases where tissue-specific, recognizable clinical syndromes or characteristic RC complex deficiencies and histochemical abnormalities are observed, direct sequencing of the specific causative nuclear gene(s) can be performed on white blood cell DNA. Measurement of mtDNA content in affected tissues such as muscle and liver allows screening for mtDNA depletion syndromes. The ever-expanding list of known disease-causing genes will undoubtedly improve diagnostic accuracy and genetic counseling. PMID- 20359922 TI - Have panoramic indices the power to identify women with low BMD at the axial skeleton? AB - The purpose of this study was to investigate whether panoramic mandibular indices i.e. mandibular cortical width (MCW), alveolar bone resorption degree (M/M ratio) and panoramic mandibular index (PMI) can be used as pre-selection tests to identify women with low bone mineral density (BMD) at the axial skeleton. MCW, PMI and M/M ratio were measured on dental panoramic radiographs in a group of 151 postmenopausal women aged 38-80 years. BMD at the lumbar spine and hip was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal, osteopenic or osteoporotic according to the WHO classification. ROC analysis was used to determine cut-off values for MCW. MCW performed better than PMI and M/M ratio in its power to differentiate women with osteopenia or osteoporosis from healthy subjects. Cut-off values for the MCW estimated to detect women with T-score < -1 and those with T-score <= -2.5 identified a total of 45% and 34% of subjects respectively. Sensitivity and specificity was found to be low ranging between 55 and 70 for both cut-off values. Panoramic indices appear to have limited power in their ability to identify women with low BMD at the axial skeleton. PMID- 20359923 TI - [Acute secondary pancreatitis to azathioprine versus autoimmune pancreatitis in a patient with ulcerative colitis]. PMID- 20359925 TI - [Drugs in elderly institutionalized patients with renal failure]. PMID- 20359926 TI - [Application of joint analysis to ongoing training of pharmacy personnel]. AB - INTRODUCTION: Ongoing training by means of clinical sessions constitutes an essential activity for a pharmacy department, being joint analysis useful to adapt the clinical sessions' characteristics to the preferences of the professionals involved. By means of this study we hope to optimize clinical sessions for their better use and efficiency. METHODS: A least squares model was used to assess the usefulness of different clinical session profiles. Data was collected from 14 individual interviews (7 specialists and 7 residents); these interviews consisted in ordering the clinical session profiles by order of preference. RESULTS: The most valued attributes were duration of sessions (29.9%) and the structure of teaching content (27.8%) in both groups studied; although the duration of the sessions was assigned greater value by the group of residents (31.1% vs. 27.2%). The availability of bibliographical references was the third attribute most valued (17.9%), and the two last attributes by order of importance were availability of a copy in files for storage (13.8%) and multimedia content (10.5%). DISCUSSION: The adaptation of clinical sessions as an integral part of ongoing training leads us to see that we can modify the duration, content structure and availability of bibliographical references so as to adapt them to the preferences of the professionals involved. However, according to the population surveyed, other attributes are of little importance. PMID- 20359927 TI - [Adverse events in emergency departments. Review of reconsultations as a data source]. AB - OBJECTIVE: To identify potential adverse events that occur in an emergency department by reviewing cases of patients who make repeat visits. METHOD: A retrospective study of clinical data of patients returning to the emergency department within a period of less than one week in October 2006 with the aim of identifying problems that occurred in the first visit. The review was conducted by senior doctors of the same service who measured the reliability of the first intervention, by checking between observer agreement. The Chi square test was used to calculate the comparison ratios. RESULTS: We studied 311 cases. Of these, 203 cases (79.6%) returned to the department without been given a previous appointment and for a reason connected with the first visit. The progress was poor in 83.7% of cases. We reviewed the causes of the poor outcomes, with the most frequent being "natural progress of the process" in 75 cases (44.1%), followed by problems in treatment in 73 cases (42.9%). The effects on the patient were evaluated, and it was shown that there were consequences for the patient in 36 cases (21.2%). Of these 36 cases, 11 were considered as avoidable (30.5%) by the evaluators and 1% of clear failures in performance in patients returning to emergency rooms. In the part of if, in opinion of the evaluadores, there had been a clear failure in the first performance zoned like such 3 cases, two with consequences for the patient and 1 without consequences. CONCLUSIONS: In the conditions of the study, the internal evaluation of the reconsultas allows to identify the adverse events occurred and know his causes. This could facilitate the learning and the improvement of the culture of security. PMID- 20359928 TI - Is it important to reduce inter- and intra-individual variations to explore insulin sensitivity? PMID- 20359929 TI - Anatomy of the septomarginal trabecula in Landrace pig hearts. AB - The limitations on the availability of organs for transplantation have aroused interest in research on xenotransplantation of whole organs or certain parts of them. Thus, studies that confirm or reject similarities between the organs of different animals have started to have important clinical applications. In the present study, we investigated the septomarginal trabecula in 34 hearts from Landrace pigs with the aim of observing their similarities with the septomarginal trabecula in humans. In pigs, the muscle bundle of the septomarginal trabecula and the right branch of the stimulating complex are dissociated. The right branch is a narrow bridge that, after going out from the upper part of the interventricular septum, is attached to the upper part of the anterior papillary muscle. On the other hand, the muscle bundle of the septomarginal trabecula is generally a resistant crest that goes from the lower part of the septum to the lower part of the anterior papillary muscle. The septomarginal trabecula presents marked anatomical differences between humans and pigs. PMID- 20359930 TI - The axillary arch - morphological and histological study with clinical importance. AB - The latissimus dorsi is a muscle of the back which forms the posterior fold of the axilla and its tendon twists to insert into the floor of the intertubercular sulcus of the humerus. Occasionally, the muscle has a muscular slip which crosses the axilla to insert into the pectoralis major. This muscular slip is often termed as "axillary arch." In the present study, we report bilateral axillary arch detected in a 45-year-old male cadaver. The average vertical length of the axillary arch measured 7 cm. The average maximum width of the uppermost, middle and lower part of the arch measured 2, 3.5 and 3.2 cm, respectively. The presence of the axillary arch is an uncommon finding in humans, considering the fact that it is solely found in the animals who prefer to hang on the trees. A histological study of the axillary arch was also performed and it showed skeletal muscle fibres which was uniformly arranged. The presence of the axillary arch may assist in the adduction of the shoulder. It may also compress the axillary vessels and nerves thereby causing resultant symptoms. Prior anatomical knowledge of the presence of axillary arch may be helpful for surgeons performing radical dissection of the axillary lymph nodes and ligation of axillary vessels, clinicians diagnosing abduction syndromes and interventional radiologists interpreting axillary mass in day to day clinical practice. PMID- 20359931 TI - [Prognostic value of pretherapeutic 18F-FDG PET/CT in cancer of the uterine cervix: a retrospective study of 53 patients]. AB - OBJECTIVES: Assessment of prognostic value of pretherapeutic (18)F-FDG PET/CT (PET). PATIENTS AND METHODS: Retrospective study of 53 patients with invasive uterine cervix carcinoma. Each patient has been evaluated with pretherapeutic whole-body FDG PET/CT and pelvic MRI. Minimal follow-up lasted for 1 year. On PET/CT, we have visually analyzed metabolism of primary tumor, pelvic and para aortic lymph nodes in comparison with surrounding structures. We have compared prognostic factors as pretherapeutic haemoglobin rate, FIGO staging, MRI and PET/CT data using Mann-Whitney univariate analysis and Cox multivariate analysis. RESULTS: Para-aortic lymph node abnormal uptake on PET/CT was the only independent predictor of progression-free survival. Pelvic lymph node involvement on PET/CT was the only independent predictor of overall survival. MRI did not provide any additional information. DISCUSSION AND CONCLUSION: Lymph node involvement visually assessed by (18)F-FDG PET/CT was the most significant prognostic factor for overall and progression-free survival. PMID- 20359932 TI - Ultrasonic-assisted transesterification of Jatropha curcus oil using solid catalyst, Na/SiO2. AB - The production of biodiesel from non-edible vegetable oil using ultrasonication, calls for an efficient solid catalyst to make the process fully ecologically and economically friendly. The methodology allows for the reaction to be run under atmospheric conditions. Solid catalyst and ultrasonication reduced the reaction time comparing to the conventional batch processes and we found 98.53% biodiesel yield. The optimal conditions for biodiesel production is the molar ratio oil to methanol 1:9, Catalyst conc. 3 wt.% of oil and 15 min reaction time. PMID- 20359933 TI - A subject specific multibody model of the knee with menisci. AB - The menisci of the knee play an important role in joint function and our understanding of knee mechanics and tissue interactions can be enhanced through computational models of the tibio-menisco-femoral structure. Several finite element models of the knee that include meniscus-cartilage contact exist, but these models are typically limited to simplified boundary conditions. Movement simulation and musculoskeletal modeling can predict muscle forces, but are typically performed using the multibody method with simplified representation of joint structures. This study develops a subject specific computational model of the knee with menisci that can be incorporated into neuromusculoskeletal models within a multibody framework. Meniscus geometries from a 78-year-old female right cadaver knee were divided into 61 discrete elements (29 medial and 32 lateral) that were connected through 6x6 stiffness matrices. An optimization and design of experiments approach was used to determine parameters for the 6x6 stiffness matrices such that the force-displacement relationship of the meniscus matched that of a linearly elastic transversely isotropic finite element model for the same cadaver knee. Similarly, parameters for compliant contact models of tibio menisco-femoral articulations were derived from finite element solutions. As a final step, a multibody knee model was developed and placed within a dynamic knee simulator model and the tibio-femoral and patello-femoral kinematics compared to an identically loaded cadaver knee. RMS errors between finite element displacement and multibody displacement after parameter optimization were 0.017 mm for the lateral meniscus and 0.051 mm for the medial meniscus. RMS errors between model predicted and experimental cadaver kinematics during a walk cycle were less than 11 mm translation and less than 7 degrees orientation. A small improvement in kinematics, compared to experimental measurements, was seen when the menisci were included versus a model without the menisci. With the menisci the predicted tibio-femoral contact force was significantly reduced on the lateral side (937 N peak force versus 633 N peak force), but no significant reduction was seen on the medial side. PMID- 20359934 TI - Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. AB - The aim of this study was to evaluate the efficacy and safety of intramuscular (IM) administration of botulinum toxin type A (Dysport((R)), Ipsen Biopharm Ltd.) for the treatment of cervical dystonia (CD) and the long-term safety and efficacy of repeated treatments. During the randomized, double-blind, placebo-controlled phase patients were randomized to 500 units Dysport (n = 55) or placebo (n = 61). Efficacy assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total and subscale scores, visual analogue scale (VAS) for pain, subject/investigator's VAS for symptom assessments. Patients completing the double-blind treatment could enter an open-label extension phase and receive up to 4 additional Dysport treatments. Dysport produced a significant decrease from baseline in mean (+/-SE) TWSTRS total scores compared with placebo at Week 4 (primary efficacy endpoint; -15.6 +/- 2.0 vs. -6.7 +/- 2.0; p < 0.001) with significant improvements sustained to Week 12 (p = 0.019). Dysport also produced significant improvements in TWSTRS subscale scores, VAS pain scores, and subject/investigator's VAS symptom assessments compared to placebo. The mean duration of open-label study participation was 51.9 weeks (range 3.9-94.0 weeks). During open-label treatment, all treatment cycles resulted in improvements in mean TWSTRS total and subscale scores at Week 4 post-treatment; greatest improvement was seen in cycle 1. The mean duration between treatment cycles was 15-17 weeks. Dysport demonstrated a good long-term safety profile; most adverse events were mild or moderate and typical of the known safety profile of Dysport in this indication. These results confirm that Dysport (500 units) is safe, effective, and well-tolerated in patients with CD. PMID- 20359935 TI - Pain catastrophizing predicts pain intensity during a neurodynamic test for the median nerve in healthy participants. AB - Psychological factors within the Fear-Avoidance Model of Musculoskeletal Pain (FAM) predict clinical and experimental pain in both symptomatic and asymptomatic individuals. Clinicians routinely examine individuals with provocative testing procedures that evoke symptoms. The purpose of this study was to investigate which FAM factors were associated with evoked pain intensity, non-painful symptom intensity, and range of motion during an upper-limb neurodynamic test. Healthy participants (n = 62) completed psychological questionnaires for pain catastrophizing, fear of pain, kinesiophobia, and anxiety prior to neurodynamic testing. Pain intensity, non-painful sensation intensity, and elbow range of motion (ROM) were collected during testing and served as dependent variables in separate simultaneous regression models. All the psychological predictors in the model accounted for 18% of the variance in evoked pain intensity (p = .02), with only pain catastrophizing (beta = .442, p < .01) contributing uniquely to the model. Psychological predictors did not explain significant amounts of variance for the non-painful sensation intensity and ROM models. These findings suggest that pain catastrophizing contributed specifically to evoked pain intensity ratings during neurodynamic testing for healthy subjects. Although these findings cannot be directly translated to clinical practice, the influence of pain catastrophizing on evoked pain responses should be considered during neurodynamic testing. PMID- 20359936 TI - Impact of order of movement on nerve strain and longitudinal excursion: a biomechanical study with implications for neurodynamic test sequencing. AB - It is assumed that strain in a nerve segment at the end of a neurodynamic test will be greatest if the joint nearest that nerve segment is moved first in the neurodynamic test sequence. To test this assumption, the main movements of the median nerve biased neurodynamic test were applied in three different sequences to seven fresh-frozen human cadavers. Strain and longitudinal excursion were measured in the median nerve at the distal forearm. Strain and relative position of the nerve at the end of a test did not differ between sequences. The nerve was subjected to higher levels of strain for a longer duration during the sequence where wrist extension occurred first. The pattern of excursion was different for each sequence. The results highlight that order of movement does not affect strain or relative position of the nerve at the end of a test when joints are moved through comparable ranges of motion. When used clinically, different neurodynamic sequences may still change the mechanical load applied to a nerve segment. Changes in load may occur because certain sequences apply increased levels of strain to the nerve for a longer time period, or because sequences differ in ranges of joint motions. PMID- 20359937 TI - Pain biology education and exercise classes compared to pain biology education alone for individuals with chronic low back pain: a pilot randomised controlled trial. AB - The aim of this single-blind pilot RCT was to investigate the effect of pain biology education and group exercise classes compared to pain biology education alone for individuals with chronic low back pain (CLBP). Participants with CLBP were randomised to a pain biology education and group exercise classes group (EDEX) [n = 20] or a pain biology education only group (ED) [n = 18]. The primary outcome was pain (0-100 numerical rating scale), and self-reported function assessed using the Roland Morris Disability Questionnaire, measured at pre intervention, post-intervention and three month follow up. Secondary outcome measures were pain self-efficacy, pain related fear, physical performance testing and free-living activity monitoring. Using a linear mixed model analysis, there was a statistically significant interaction effect between time and intervention for both pain (F[2,49] = 3.975, p < 0.05) and pain self-efficacy (F[2,51] = 4.011, p < 0.05) with more favourable results for the ED group. The effects levelled off at the three month follow up point. In the short term, pain biology education alone was more effective for pain and pain self-efficacy than a combination of pain biology education and group exercise classes. This pilot study highlights the need to investigate the combined effects of different interventions. PMID- 20359939 TI - Advances in modifying lignin for enhanced biofuel production. AB - Renewable and sustainable liquid transportation biofuels based on lignocellulosics conversion face several obstacles that must be overcome in order for them to become commercially viable and cost-competitive. The presence of lignin is one of the most significant contributors to biomass recalcitrance and consequently increases the costs associated with conversion. Lignins are complex aromatic biopolymers, derived from hydroxyphenylpropanoids, that vary in composition and structure as a function of genotype, phenotype, and environment, as well as with the cell type and maturity of the plant tissue. Lignins consist of (mainly) syringyl (S), guaiacyl (G), and p-hydroxyphenyl (H) units, derived from sinapyl, coniferyl, and p-coumaryl alcohols. These units are not discrete within either the cell or a given lignin molecule, and the compositional ratios of these three moieties can vary significantly. This inherent complexity and heterogeneity of lignin, both in structure and composition, make it extremely difficult to develop a conversion technology that can efficiently process a wide range of sustainable feedstocks cost-effectively. There is a growing body of work that has demonstrated several genetic engineering strategies that, when coupled with an integrated approach to conversion, hold significant promise for the development of tailored feedstocks designed for biofuel production. The knowledgebase is at the point where researchers are also able to contemplate strategies to 'design' the lignin polymer for easier processing. The realization of advanced analytical techniques and an increasing number of plant genomes are enabling researchers to take a systems approach towards understanding and engineering lignin to develop these optimal feedstocks. PMID- 20359938 TI - Optimisation of orthopaedic implant design using statistical shape space analysis based on level sets. AB - Statistical shape analysis techniques have shown to be efficient tools to build population specific models of anatomical variability. Their use is commonplace as prior models for segmentation, in which case the instance from the shape model that best fits the image data is sought. In certain cases, however, it is not just the most likely instance that must be searched, but rather the whole set of shape instances that meet certain criterion. In this paper we develop a method for the assessment of specific anatomical/morphological criteria across the shape variability found in a population. The method is based on a level set segmentation approach, and used on the parametric space of the statistical shape model of the target population, solved via a multi-level narrow-band approach for computational efficiency. Based on this technique, we develop a framework for evidence-based orthopaedic implant design. To date, implants are commonly designed and validated by evaluating implant bone fitting on a limited set of cadaver bones, which not necessarily span the whole variability in the population. Based on our framework, we can virtually fit a proposed implant design to samples drawn from the statistical model, and assess which range of the population is suitable for the implant. The method highlights which patterns of bone variability are more important for implant fitting, allowing and easing implant design improvements, as to fit a maximum of the target population. Results are presented for the optimisation of implant design of proximal human tibia, used for internal fracture fixation. PMID- 20359940 TI - Systematic investigation of the influence of CdTe QDs size on the toxic interaction with human serum albumin by fluorescence quenching method. AB - Quantum dots (QDs) are complementary tools to the organic fluorescent dyes used in biological system. Investigation of QDs biological toxicity has attracted great interest for their depth application. Here, the fluorescence quenching method was used to investigate the influence of CdTe QDs size on the toxic interaction with human serum albumin (HSA). Two aqueous-compatible CdTe QDs with maximum emission of 535nm (green-emitting QDs, G-QDs, 2.04 nm) and 654 nm (red emitting QDs, R-QDs, 3.79 nm) were tested. The fluorescence quenching results indicated that the quenching effect of QDs on HSA fluorescence depended on the size and the nature of quenching is not dynamic but probably static, resulting in forming QDs-HSA complexes. The binding constants and the number of binding sites between R-QDs and HSA were higher than those of G-QDs. The results illustrated that the size of CdTe quantum dots affected the affinity for HSA and the increasing size of QDs enhanced the affinity for HSA. The values of lgK(a) are proportional to the number of binding sites (n). This result confirms the method used here is suitable to study the toxic interaction between QDs and HSA. PMID- 20359941 TI - Iron-oxide aerogel and xerogel catalyst formulations: characterization by 57Fe Mossbauer and XAFS spectroscopies. AB - Iron in various iron-oxide aerogel and xerogel catalyst formulations (> or =85% Fe(2)O(3); < or =10% K, Co, Cu, or Pd) developed for possible use in Fischer Tropsch synthesis (FTS) or the water-gas-shift (WGS) reaction has been examined by (57)Fe Mossbauer spectroscopy. The seventeen samples consisted of both as prepared and calcined aerogels and xerogels and their products after use as catalysts for FTS or the WGS reaction. Complementary XAFS spectra were obtained on the occurrence of the secondary elements in some of the same materials. A broad, slightly asymmetric, two-peak Mossbauer spectrum was obtained from the different as-prepared and calcined catalyst formulations in the majority of cases. Such spectra could only be satisfactorily fit with three quadrupole doublet components, but no systematic trends in the isomer shift and quadrupole splitting parameters and area ratios of the individual components could be discerned that reflected variations in the composition or preparation of the aerogel or xerogel materials. However, significant reductions were noted in the Mossbauer effective thickness (recoilless absorption effect per unit mass of iron) parameter, chi(eff)/g, determined at room temperature, for aerogels and xerogels compared to bulk iron oxides, reflecting the openness and lack of rigidity of the aerogel and xerogel structures. Mossbauer measurements for two aerogels over the range from 15 to 292K confirmed the greatly diminished nature of this parameter at room temperature. Major increases in the effective thickness parameter were observed when the open structure of the aerogel or xerogel collapsed during calcination resulting in the formation of iron oxides (hematite, spinel ferrite). Similar structural changes were indicated by increases in this parameter after use of iron-oxide aerogels as catalysts for FTS or the WGS reaction, during which the iron-oxide aerogel was converted to a mixture of nonstoichiometric magnetite and the Hagg carbide, chi-Fe(5)C(2), or nonstoichiometric magnetite, respectively. PMID- 20359942 TI - A search for activation of C nociceptors by sympathetic fibers in complex regional pain syndrome. AB - OBJECTIVE: Although the term 'reflex sympathetic dystrophy' has been replaced by 'complex regional pain syndrome' (CRPS) type I, there remains a widespread presumption that the sympathetic nervous system is actively involved in mediating chronic neuropathic pain ["sympathetically maintained pain" (SMP)], even in the absence of detectable neuropathophysiology. METHODS: We have used microneurography to evaluate possible electrophysiological interactions in 24 patients diagnosed with CRPS I (n=13), or CRPS II (n=11) by simultaneously recording from single identified sympathetic efferent fibers and C nociceptors, while provoking sympathetic neural discharges in cutaneous nerves. RESULTS: We assessed potential effects of sympathetic activity upon 35 polymodal nociceptors and 19 mechano-insensitive nociceptors, recorded in CRPS I (26 nociceptors) and CRPS II patients (28 nociceptors). No evidence of activation of nociceptors related to sympathetic discharge was found, although nociceptors in six CRPS II patients exhibited unrelated spontaneous pathological nerve impulse activity. CONCLUSIONS: We conclude that activation of nociceptors by sympathetic efferent discharges is not a cardinal pathogenic event in either CRPS I or CRPS II patients. SIGNIFICANCE: This study shows that sympathetic-nociceptor interactions, if they exist in patients communicating chronic neuropathic pain, must be the exception. PMID- 20359943 TI - The effects of healthy aging on auditory processing in humans as indexed by transient brain responses. AB - OBJECTIVE: The aim of the study was to investigate the effects of aging on human cortical auditory processing of rising-intensity sinusoids and speech sounds. We also aimed to evaluate the suitability of a recently discovered transient brain response for applied research. METHODS: In young and aged adults, magnetic fields produced by cortical activity elicited by a 570-Hz pure-tone and a speech sound (Finnish vowel /a/) were measured using MEG. The stimuli rose smoothly in intensity from an inaudible to an audible level over 750 ms. We used both the active (attended) and the passive recording condition. In the attended condition, behavioral reaction times were measured. RESULTS: The latency of the transient brain response was prolonged in the aged compared to the young and the accuracy of behavioral responses to sinusoids was diminished among the aged. In response amplitudes, no differences were found between the young and the aged. In both groups, spectral complexity of the stimuli enhanced response amplitudes. CONCLUSIONS: Aging seems to affect the temporal dynamics of cortical auditory processing. The transient brain response is sensitive both to spectral complexity and aging-related changes in the timing of cortical activation. SIGNIFICANCE: The transient brain responses elicited by rising-intensity sounds could be useful in revealing differences in auditory cortical processing in applied research. PMID- 20359945 TI - Sleep quality in CCU patients after controlling for environmental factors. PMID- 20359946 TI - Leishmanolysin-like molecules in Herpetomonas samuelpessoai mediate hydrolysis of protein substrates and interaction with insect. AB - Herpetomonas samuelpessoai, an insect trypanosomatid, produces a 63-kDa metallopeptidase that has similar biochemical/immunological properties to Leishmania leishmanolysin, a virulence factor that participates in different stages of the parasite life cycle. Herein, we described some biochemical characteristics of the major surface metallopeptidase of H. samuelpessoai that led us to infer some probable functions for this peptidase during the parasite invertebrate interaction. Gelatin-SDS-PAGE, flow cytometry and confocal fluorescence microscopy provided measurements for the relative levels of surface leishmanolysin-like molecules in H. samuelpessoai. Immunocytochemical analysis demonstrated the presence of leishmanolysin-like molecules on the surface and cytoplasm of the parasite. The surface metallopeptidase was active at a broad spectrum of pH and temperature, showing maximum activity at pH 6.0 at 37 degrees C, and an ability to degrade albumin, hemoglobin, IgG, mucin, casein and gut proteins obtained from Aedes aegypti. This wide substrate utilization might support parasite growth and development. Curiously, H. samuelpessoai cells were able to colonize A. aegypti guts. In an effort to implicate a possible role for the metallopeptidase from H. samuelpessoai, living parasites were treated with different compounds before the interaction with gut cells. The pre-incubation with metallopeptidase inhibitors, phospholipase C or anti-leishmanolysin antibodies promoted a significant reduction in the interaction with guts. Similarly, the pre-treatment of gut cells with purified leishmanolysin-like protein drastically diminished the adhesion process. Furthermore, the expression of surface leishmanolysin in H. samuelpessoai cells was drastically enhanced after passage in A. aegypti. These results suggest the participation of homologues of leishmanolysin in the interaction of H. samuelpessoai with the invertebrate vector. PMID- 20359944 TI - Cellular and chemical neuroscience of mammalian sleep. AB - Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. PMID- 20359947 TI - A functional variant within the MMP3 gene does not associate with human range of motion. AB - A recent heritability study has demonstrated that human range of motion (ROM) has a substantial genetic component. Furthermore, the COL5A1BstUI RFLP has now been identified as the first gene variant to be associated with human ROM. Interestingly, this variant is known to interact with a functional variant within the MMP3 gene (rs679620) to increase risk of Achilles tendinopathy. We sought to determine whether the MMP3 rs679620 variant was associated with ROM both as a single marker and as an interacting marker with the COL5A1 BstUI RFLP. One hundred and twenty one participants were included in this study. All participants were genotyped for the MMP3 rs679620 variant, and performed passive straight leg raise (SLR) and sit and reach (SR) measurements. There were no significant differences in left leg SLR (L-SLR), right leg SLR (R-SLR), or SR measurements between the genotype groups (L-SLR, P=0.494; R-SLR, P=0.435; SR, P=0.266). Furthermore, there was no evidence of an interaction between the COL5A1 BstUI RFLP and the MMP3 rs679620 variant. Our study suggests that the MMP3 rs679620 variant does not associate with passive ROM. PMID- 20359948 TI - Change in running kinematics after cycling are related to alterations in running economy in triathletes. AB - Emerging evidence suggests that cycling may influence neuromuscular control during subsequent running but the relationship between altered neuromuscular control and run performance in triathletes is not well understood. The aim of this study was to determine if a 45 min high-intensity cycle influences lower limb movement and muscle recruitment during running and whether changes in limb movement or muscle recruitment are associated with changes in running economy (RE) after cycling. RE, muscle activity (surface electromyography) and limb movement (sagittal plane kinematics) were compared between a control run (no preceding cycle) and a run performed after a 45 min high-intensity cycle in 15 moderately trained triathletes. Muscle recruitment and kinematics during running after cycling were altered in 7 of 15 (46%) triathletes. Changes in kinematics at the knee and ankle were significantly associated with the change in VO(2) after cycling (p<0.05). The change in ankle angle at foot contact alone explained 67.1% of the variance in VO(2). These findings suggest that cycling does influence limb movement and muscle recruitment in some triathletes and that changes in kinematics, especially at the ankle, are closely related to alterations in running economy after cycling. PMID- 20359949 TI - Epo production at altitude in elite endurance athletes is not associated with the sea level hypoxic ventilatory response. AB - The level of circulating erythropoietin (EPO) in response to a fixed level of hypoxia shows substantial inter-individual variability, the source of which is undetermined. Arterial PO(2) at altitude is regulated in part by the hypoxic ventilatory response, which also shows a wide inter-individual variability. We asked if the ventilatory response to hypoxia is related to the magnitude of EPO release at moderate altitude. Twenty-six national class US distance runners (17 M, 9 F) participated in a test of isocapnic hypoxic ventilatory response (HVR) at sea level, 2-7 days prior to departure to altitude. EPO measures were obtained at sea level and after 20 h at 2500 m. HVR for all subjects was 0.21+/-0.16 L min-1 %SaO2-1 (range 0.01-0.61 L min-1 %SaO2-1), with no significant difference between men and women. EPO was significantly increased from pre-altitude (8.6+/-2.6 ng ml(-1), range 4.0-14.6 ng ml-1) to acute altitude (16.6+/-4.4 ng ml-1, range 5.0 27.0 ng ml-1), an increase of 92.2+/-70.1%. There was no significant sex difference in the EPO increase. DeltaEPO for all subjects was not correlated with HVR (r=-0.17). Similarly, a statistically or physiologically significant correlation was not present between DeltaEPO and HVR within the group of men (r= 0.22) or women (r=-0.19). The variability in the acute EPO response to moderate altitude is not explained by differences in peripheral chemoresponsiveness in elite distance runners. These results suggest that factors acting downstream from the lung influence the magnitude of the acute EPO response to altitude. PMID- 20359950 TI - Cardiovascular health in indigenous communities: successful programs. AB - BACKGROUND: Indigenous people across the globe have generally had suboptimal access to quality medical care and effective prevention programs. The available programs that existed have generally been poorly funded and have primarily focussed on infectious diseases. More recent trends denoting significant rising morbidity and mortality of chronic diseases have brought some limited medical focus on cardiovascular diseases, their risk factors and their prevention. However, there is a growing body of evidence-published and unpublished-of developed and developing successful programs to provide culturally appropriate and sensitive treatment for cardiovascular diseases and prevention. Within this report, we aim to describe some of these programs in order to understand common approaches and links that make them successful. Once this survey is completed, a template for successful CVD programs can be created for the development of future programs. METHODS: We used several methods to gather information about successful Indigenous CVD programs: Pub Med search (keywords: Indigenous, native, First Nation, Aboriginal, cardiovascular, cardiac, etc.), online searches of government based health programs (World Health Organization, Centers for Disease Control, etc.) and non-government health programs (World Heart Federation, Bill & Melinda Gates Foundation, etc.), and, importantly, personal communication with multiple thought leaders and program directors in the field of international CVD treatment and prevention. RESULTS: Programs can be divided into: (1) epidemiologic programs, which focus on data collection, (2) focussed prevention programs and population approach to CVD prevention, and (3) clinical prevention and intervention programs. DISCUSSION: Common themes that define successful Indigenous CVD programs include: dedicated focus on the Indigenous population, widespread community involvement within the Indigenous population, often through the use of Indigenous community health workers, a focus on high-risk individuals within the population and regularly scheduled contact between the program and participants. We recommend that these themes are incorporated during development of future CVD programs for Indigenous people. PMID- 20359952 TI - Giant pulmonary hamartoma: an interesting clinico-pathologic entity. PMID- 20359951 TI - Improving cardiovascular care for indigenous populations. AB - The challenges and opportunities for provision of, and access to, reliable chronic cardiovascular health care for Indigenous people were addressed by expert speakers from New Zealand and Australia. It is well recognised that cardiovascular disease is a life-long concern, requiring reliable follow-up, early transition of clinical research into practice and ongoing support of patients. The clinical outcomes and long-term prognosis of individuals with cardiovascular disease are critically dependent upon the quality and availability of follow-up and chronic care facilities. This paper summarises the principal issues identified by the expert speakers for the provision of chronic cardiovascular health care to Indigenous peoples in Australia and New Zealand; identifies common challenges and describes important initiatives which the Cardiac Society of Australia and New Zealand (CSANZ), in partnership with health care professionals, communities and governments, can undertake in order to achieve the goals of uniform and equitable health care for chronic cardiovascular disease in all the Indigenous peoples, relevant to the needs of these peoples, in New Zealand and Australia. The issues addressed by the meeting include: 1) Determination of appropriate models for effective delivery of cardiovascular health care. (2) Who should deliver cardiovascular health care and what are the workforce requirements. (3) What support systems and infrastructure are required. (4) How can primary care and secondary specialist services be effectively integrated. PMID- 20359953 TI - Fertility and clinical outcome after bowel resection in infertile women with endometriosis. AB - Bowel resection for endometriosis improves pain symptoms and quality of life in symptomatic women. However, little is known about fertility after surgery, particularly after such treatment in women suffering from infertility. The aim of the present study was to evaluate post-operative fertility and long-term clinical outcome after laparoscopic colorectal resection for endometriosis in infertile women. This study reports clinical outcomes in 62 infertile women who underwent laparoscopic excision of endometriosis with segmental bowel resection performed for severe intestinal symptoms. Among women younger than 30 years trying to conceive spontaneously, the cumulative pregnancy rate was 58% and the cumulative pregnancy rate was 45% in those aged 30-34 years. The total pain recurrence was 9.7% (six cases) and endometriosis recurrence was diagnosed by ultrasound in 14.5% (nine cases) during the follow-up period. Four of these patients needed further surgery because of severe symptoms. The surgical treatment of bowel endometriosis seems to improve pain symptoms and patients' satisfaction rates, and it could also be indicated in infertile women. PMID- 20359954 TI - Antibody and cytokine responses to house dust mite allergens and Toxoplasma gondii antigens in atopic and non-atopic Brazilian subjects. AB - According to hygiene hypothesis, a lower exposure to infection is associated with increased prevalence of allergic diseases. This study aimed to investigate the association between atopy and Toxoplasma gondii (Tg) infection by analyzing the antibody and cytokine responses to house dust mite allergens and T. gondii antigens in Brazilian subjects. A total of 275 individuals were assessed and divided into atopics (n=129) and non-atopics (n=146) based on markers of allergy (positive skin prick test and ELISA-IgE to mite allergens) or Tg-seropositive (n=116) and Tg-seronegative (n=159) groups according to infection markers (positive ELISA-IgG to T. gondii). Tg-seropositive individuals presented lower allergenic sensitization (37%) to mite allergens than Tg-seronegative subjects (54%). A significant association was found between atopy and negative serology to T. gondii (OR: 2.0; 95% CI: 1.23-3.26; P<0.05). Proliferative responses and cytokine production after antigenic stimulation showed predominant synthesis of Th1-cytokines as IFN-gamma in Tg-seropositive patients, whether atopics or non atopics. Conversely, Th2-cytokines as IL-5 prevailed in atopics compared to non atopics, regardless the seropositivity to T. gondii. Levels of IL-10, IL-13, IL 17, and TGF-beta were not able to discriminate the groups. Hence, a negative association between atopy and infection by T. gondii was demonstrated for the first time in Brazilian subjects, focusing on the antibody and cytokine responses and indicating that the immunomodulation induced by the parasite may play a protective role in the development of allergic diseases. PMID- 20359955 TI - Administration of a determinant of preproinsulin can induce regulatory T cells and suppress anti-islet autoimmunity in NOD mice. AB - Antigen-specific immunotherapy is expected to be an ideal strategy for treating type 1 diabetes (T1D). We investigated the therapeutic efficacy of a peptide in the leader sequence of preproinsulin, which was selected because of its binding affinity to the MHC I-A(g7) molecule. Preproinsulin-1 L7-24 peptide (L7-24) emulsified in Freund's incomplete adjuvant was administered subcutaneously to NOD mice. Administration of L7-24 increased the proportion of regulatory T cells in the spleen. Splenocytes of NOD mice immunized with this peptide secreted IL-4 and IL-10 in response to L7-24. This peptide also significantly prevented the development of diabetes and cured some newly diabetic NOD mice without recurrence. L7-24 peptide, which has a high affinity for pockets of I-A(g7), induced regulatory T cells and showed therapeutic effects. This peptide may provide a new approach for developing antigen-specific immunotherapy for autoimmune diabetes. PMID- 20359956 TI - CD161 receptor participates in both impairing NK cell cytotoxicity and the response to glycans and vimentin in patients with rheumatoid arthritis. AB - We investigated the role of natural killer (NK) cells and CD161, their primary C type-lectin-like receptor in rheumatoid arthritis (RA). Samples were compared with healthy donors (HD), dermatomyositic (DM), polymyositic (PM), and osteoarthritic (OA) patients. RA, PM, and DM NK cell cytotoxicities significantly decreased relative to the HD and OA NK cells (p<0.0001). These results correlated with an increased expression of NK cell inhibitory receptor CD161, in active disease RA patients. We demonstrated that NK cells are able to respond to mutated citrullinated vimentin (MCV), an RA-specific autoantigen, leading to increases in both PAD4 enzyme and CD161 mRNA expression. MGAT5 glycosidase involvement was detected in GlcNAc metabolism within the synoviocytes of RA patients. Our findings reveal a functional relationship between CD161 expression and NK cell cytotoxicity as well as reactivity to glycans and MCV, thus providing new insight into the pathogenesis of RA and confirming the involvement of surface glycosylation. PMID- 20359957 TI - Three-dimensional dynamic in vivo motion of the cervical spine: assessment of measurement accuracy and preliminary findings. AB - BACKGROUND CONTEXT: Previous research has quantified cervical spine motion with conventional measurement techniques (eg, cadaveric studies, motion capture systems, and fluoroscopy), but these techniques were not designed to accurately measure three-dimensional (3D) dynamic cervical spine motion under in vivo conditions. PURPOSE: The purposes of this study were to characterize the accuracy of model-based tracking for measuring 3D dynamic cervical spine kinematics and to demonstrate its in vivo application. STUDY DESIGN: Through accuracy assessment and application of technique, in vivo cervical spine motion was measured. METHODS: The accuracy of model-based tracking for measuring cervical spine motion was determined in an in vitro experiment. Tantalum beads were implanted into the vertebrae of an ovine specimen, and biplane X-ray images were acquired as the specimen's neck was manually moved through neck extension and axial neck rotation. The 3D position and orientation of each cervical vertebra were determined from the biplane X-ray images using model-based tracking. For comparison, the position and orientation of each vertebra were also determined by tracking the position of the implanted beads with dynamic radiostereometric analysis. To demonstrate in vivo application of this technique, biplane X-ray images were acquired as a human subject performed two motion tasks: neck extension and axial neck rotation. The positions and orientations of each cervical vertebra were determined with model-based tracking. Cervical spine motion was reported with standard kinematic descriptions of translation and rotation. RESULTS: The in vitro validation demonstrated that model-based tracking is accurate to within +/-0.6 mm and +/-0.6 degrees for measuring cervical spine motion. For the in vivo application, there were significant rotations about all three anatomical axes for both the neck extension and axial neck rotation motion tasks. CONCLUSIONS: Model-based tracking is an accurate technique for measuring in vivo, 3D, dynamic cervical spine motion. Preliminary data acquired using this technique are in agreement with previous studies. It is anticipated that this experimental approach will enhance our understanding of cervical spine motion under normal and pathologic conditions. PMID- 20359958 TI - Neck Disability Index, short form-36 physical component summary, and pain scales for neck and arm pain: the minimum clinically important difference and substantial clinical benefit after cervical spine fusion. AB - BACKGROUND CONTEXT: The Neck Disability Index (NDI), the short form-36 (SF-36) physical component summary (PCS), and pain scales for arm and neck pain are increasingly used to evaluate treatment effectiveness after cervical spine surgery. The minimum clinically important difference (MCID) is a threshold of improvement that is clinically relevant to the patient. However, the true goal is to provide the patient with a substantial clinical benefit (SCB). PURPOSE: This study determines the MCID and SCB using common anchor-based methods for NDI, PCS, and pain scales for arm and neck pain in patients undergoing cervical spine fusion for degenerative disorders. STUDY DESIGN/SETTING: The study setting is a longitudinal cohort in a multisurgeon spine specialty clinic. PATIENT SAMPLE: The sample comprises 505 patients who underwent a cervical fusion for degenerative spine conditions and who have prospectively collected outcome scores with a minimum 1-year follow-up. OUTCOME MEASURES: The outcome measures of the study were NDI, SF-36, and numeric rating scales for arm and neck pain. METHODS: The MCID and SCB values for NDI, PCS, and pain scales for arm and neck pain were determined using receiver operating characteristic (ROC) curve analysis with the Health Transition Item of the SF-36 as an anchor. The Health Transition Item asks a patient "Compared to one year ago, how would you rate your health in general now?" with answers ranging from "Much Better," "Somewhat Better," "About the Same," "Somewhat Worse," to "Much Worse." An ROC curve was constructed for each measure. The ROC curve-derived MCID was the change score with equal sensitivity and specificity to distinguish the "Somewhat Better" from the "About the Same" patients. The ROC curve-derived SCB was the change score with equal sensitivity and specificity to distinguish the "Much Better" from the "Somewhat Better" patients. Distribution-based methods including the standard error of the mean and the minimum detectable change were also used to calculate MCID. RESULTS: The calculated MCID is 7.5 for the NDI, 4.1 for SF-36 PCS, and 2.5 for arm and neck pain. The calculated SCB is 9.5 for the NDI, 6.5 for SF-36 PCS, and 3.5 for arm and neck pain. CONCLUSIONS: Patients with an eight-point decrease in NDI, a 4.1 point increase in PCS, and a three-point decrease in arm or neck pain can detect a minimally clinically important change. Patients with a 10-point decrease in NDI, a 6.5-point increase in PCS, and a four-point decrease in arm or neck pain can detect an SCB after cervical spine fusion. PMID- 20359959 TI - Reliability assessment of Cobb angle measurements using manual and digital methods. AB - BACKGROUND CONTEXT: The vertebral spine angle in the frontal plane is an important parameter in the assessment of scoliosis and may be obtained from panoramic X-ray images. Technological advances have allowed for an increased use of digital X-ray images in clinical practice. PURPOSE: In this context, the objective of this study is to assess the reliability of computer-assisted Cobb angle measurements taken from digital X-ray images. STUDY DESIGN/SETTING: Clinical investigation quantifying scoliotic deformity with Cobb method to evaluate the intra- and interobserver variability using manual and digital techniques. PATIENT SAMPLE: Forty-nine patients diagnosed with idiopathic scoliosis were chosen based on convenience, without predilection for gender, age, type, location, or magnitude of the curvature. OUTCOME MEASURES: Images were examined to evaluate Cobb angle variability, end plate selection, as well as intra- and interobserver errors. METHODS: Specific software was developed to digitally reproduce the Cobb method and calculate semiautomatically the degree of scoliotic deformity. During the study, three observers estimated the Cobb angle using both the digital and the traditional manual methods. RESULTS: The results showed that Cobb angle measurements may be reproduced in the computer as reliably as with the traditional manual method, in similar conditions to those found in clinical practice. CONCLUSIONS: The computer-assisted method (digital method) is clinically advantageous and appropriate to assess the scoliotic curvature in the frontal plane using Cobb method. PMID- 20359960 TI - Cost and use of conservative management of lumbar disc herniation before surgical discectomy. AB - BACKGROUND CONTEXT: Lumbar discectomy is one of the most common spine surgical procedures. With the exception of true emergencies (eg, cauda equina syndrome), lumbar discectomy is usually performed as an elective procedure after a prudent trial of nonoperative treatment. Although several studies have compared costs of definitive operative or nonoperative management of lumbar disc herniation, no information has been published regarding the cost of conservative care in patients who ultimately underwent surgical discectomy. PURPOSE: The purpose of this study was to determine the financial costs (and relative distribution of those costs) associated with the nonoperative management of lumbar disc herniation in patients who ultimately failed conservative care and elected to undergo surgical discectomy. STUDY DESIGN: This is a retrospective database review. PATIENT SAMPLE: The sample comprises patients within the database who underwent lumbar discectomy. OUTCOME MEASURES: The outcome measures were frequency of associated procedures and the costs of those procedures. MATERIALS AND METHODS: A search was conducted using a commercially available online database of insurance records of orthopedic patients to identify all patients within the database undergoing lumbar discectomy between 2004 and 2006. Patients were identified by American Medical Association Current Procedural Terminology code. The associated charge codes for the 90-day period before the surgery were reviewed and categorized as outpatient physician visits, imaging studies, physical therapy, injection, chiropractic manipulation, medication charges, preoperative studies, or miscellaneous charges. The frequency of each code and the percentage of patients for whom that code was submitted to the insurance companies were noted, as were the associated charges. RESULTS: In total, 30,709 patients in the database met eligibility criteria. A total of $105,799,925 was charged during the 90 days preoperatively, an average of $3,445 per patient. Average charge for discectomy procedure was $7,841. Charges for injection procedures totaled $16,211,246 or 32% of total charges, diagnostic imaging $15,648,769 (31%), outpatient visits $6,552,135 (13%), physical therapy visits $5,723,644 (11%), chiropractic manipulation $1,177,406 (2%), preoperative studies $426,976 (0.8%), medications $263,039 (0.5%), and miscellaneous charges $1,177,371 (2%). CONCLUSIONS: Charges for preoperative care of patients with lumbar disc herniation are substantial and are split almost evenly between diagnostic charges (outpatient visits, imaging, laboratory studies, and miscellaneous) and therapeutic charges (injections, physical therapy, chiropractic manipulation, and medications). Although a large number of patients will ultimately require surgical intervention, given that many patients will improve with nonoperative therapy, a trial of conservative management is appropriate. Additional studies to identify patients who may ultimately fail nonoperative treatment and would benefit from early discectomy would be beneficial. PMID- 20359961 TI - Acupuncture, psyche and the placebo response. AB - With growing use of acupuncture treatment in various clinical conditions, the question has been posed whether the reported effects reflect specific mechanisms of acupuncture or whether they represent placebo responses, as they often are similar in effect size and resemble similarities to placebo analgesia and its mechanisms. We reviewed the available literature for different placebos (sham procedures) used to control the acupuncture effects, for moderators and potential biases in respective clinical trials, and for central and peripheral mechanisms involved that would allow differentiation of placebo effects from acupuncture and sham acupuncture effects. While the evidence is still limited, it seems that biological differences exist between a placebo response, e.g. in placebo analgesia, and analgesic response during acupunture that does not occur with sham acupuncture. It seems advisable that clinical trials should include potential biomarkers of acupuncture, e.g. measures of the autonomic nervous system function to verify that acupuncture and sham acupuncture are different despite similar clinical effects. PMID- 20359963 TI - A survey of exercise testing and training in UK cystic fibrosis clinics. AB - BACKGROUND: Exercise testing is a valuable prognostic tool and exercise training has many health benefits in cystic fibrosis (CF). The objective of this study was to survey the provision of exercise testing and training in UK CF clinics. METHODS: A three-page questionnaire was used to determine the extent of, scope and importance assigned to exercise testing and training. RESULTS: Data from returned questionnaires showed that 38.9% of paediatric and 27.8% of adult patients had performed an exercise test in the preceding 12 months, most as part of an annual review process. Pulmonary rehabilitation programmes were accessible in only 31.3% of clinics, and only 26.0% provide exercise training programmes. When assigning importance for exercise testing on a scale from 1 'not important' to 5 'very important', the mean and median respondent scores were 3.5 and 4.0, respectively, and for the importance of training were 4.0 and 4.0, respectively. CONCLUSIONS: Despite the level of importance given to exercise testing and training by healthcare providers, exercise is underused as either an assessment tool or therapeutic intervention in the healthcare of patients with CF in the UK. PMID- 20359962 TI - Clinical utility of the oxygen uptake efficiency slope in cystic fibrosis patients. AB - BACKGROUND: The present study investigated the validity and the reliability of the oxygen uptake efficiency slope (OUES) as a determinant of exercise tolerance in adults with cystic fibrosis (CF). METHODS: 31 CF patients and 34 healthy controls performed a maximal incremental cycle test with respiratory gas-exchange measurements. OUES was calculated from data taken from different percentages of the entire exercise duration, including 80% (OUES(80)) and 100% (OUES(100)). Peak oxygen uptake (VO(2peak)) and gas exchange threshold (GET) were also determined. The agreement between submaximal parameters and VO(2peak) was assessed using Bland Altman plots. Test retest reliability was evaluated in CF patients using absolute (SEM) and relative indices (ICC). RESULTS: On the contrary to the GET, which was undetectable in 16% of the CF patients, the OUES was easily determined in all patients. Among all the submaximal variables, OUES(80) had the best reliability (ICC=0.94, SEM=7.3%) and agreement with VO(2peak) (r(2)=0.83, P<0.01; limits of agreement: +/-365mL min(-1)) and did not differ from OUES(100). CONCLUSIONS: OUES(80) is a reliable and more useful submaximal parameter than the GET and may find use in the interpretation of exercise studies in CF patients who are unable to perform maximal exercise. PMID- 20359964 TI - A qualitative study of physiotherapy education for parents of toddlers with cystic fibrosis. AB - BACKGROUND: Education and daily physiotherapy are often highlighted as difficult and stressful tasks for parents of young children with cystic fibrosis. This study aimed to identify factors that impair the delivery and retention of physiotherapy education for parents of these children and factors that impair effective physiotherapy treatment in the home environment. METHODS: A focus group of physiotherapists and six semi-structured interviews of parents with children with cystic fibrosis were conducted. The qualitative method of Grounded Theory was used to analyse the information and develop key themes. RESULTS: Major emergent themes were 'transitions', 'psychological distress' and 'connectedness'. Factors influencing the effectiveness of parental physiotherapy education include the large volumes of information, appropriateness of educational resources and timing of education. Factors influencing home physiotherapy management for toddlers include mastering techniques, the transition from infant to toddler and time management. CONCLUSION: Physiotherapy education and management were key causes of psychological distress for parents. This research suggests that significant targeted development of educational resources is warranted, in conjunction with dedicated and ongoing formal psychosocial support for parents. PMID- 20359965 TI - Simultaneous speciation of selenomethionine and 2-hydroxy-4-methylselenobutanoic acid by HPLC-ICP MS in biological samples. AB - An analytical method was developed for the simultaneous speciation of selenomethionine (SeMet) and 2-hydroxy-4-methylselenobutanoic acid (NutraSelen), a new SeMet precursor. The compounds could be baseline resolved by ion-pairing reversed-phase HPLC using ICP MS detection. Detection limits of 1 ng mL(-1) (Se content) could be reached. SELM-1 reference material was used to validate the SeMet measurement. Additionally, the quantification of NutraSelen was validated by standard addition together with checking the Se mass balance. The procedure developed was then applied to the monitoring of the conversion of NutraSelen into SeMet by yeast. PMID- 20359966 TI - Determination of picamilon concentration in human plasma by liquid chromatography tandem mass spectrometry. AB - A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of picamilon concentration in human plasma. Picamilon was extracted from human plasma by protein precipitation. High performance liquid chromatography separation was performed on a Venusil ASB C(18) column with a mobile phase consisting of methanol -10mM ammonium acetate-formic acid (55:45:01, v/v/v) at a flow rate of 0.65ml/min. Acquisition of mass spectrometric data was performed in selected reaction monitoring mode, using the transitions of m/z 209.0-->m/z (78.0+106.0) for picamilon and m/z 152.0-->m/z (93.0+110.0) for paracetamol (internal standard). The method was linear in the concentration range of 1.00-5000ng/ml for the analyte. The lower limit of quantification was 1.00ng/ml. The intra- and inter-assay precision were below 13.5%, and the accuracy was between 99.6% and 101.6%. The method was successfully applied to characterize the pharmacokinetic profiles of picamilon in healthy volunteers. This validated LC-MS/MS method was selective and rapid, and is suitable for the pharmacokinetic study of picamilon in humans. PMID- 20359967 TI - Somatic mutation in the ACK1 ubiquitin association domain enhances oncogenic signaling through EGFR regulation in renal cancer derived cells. AB - Activated Cdc42-associated Kinase, ACK1, is a non-receptor tyrosine kinase with numerous interacting partners, including Cdc42 and EGFR. Gene amplification and overexpression of ACK1 were found in many cancer types such as those of the lung and prostate. Previously, we identified both somatic- and germ line missense mutations in the ACK1 coding sequence, by surveying 261 cancer cell lines and 15 control tissues. Here, we verified and characterized the non-synonymous mutation, ACK-S985 N, located in the ubiquitin association domain of the protein. Both overexpression and silencing experiments in MCF7 and A498 cells, respectively, demonstrated a role of the ACK1 S985 N mutation in enhancing cell proliferation, migration and anchorage-independent growth as well as the epithelial-mesenchymal transition. Further, we showed that the ACK1 S985 N mutant is unable to bind ubiquitin, unlike the wild type kinase. This contributed to ACK1 protein stability and stabilized EGFR after EGF stimulation, thereby prolonging mitogenic signaling in cancer cells. In addition, the ACK1 S985 N-EGFR interaction is enhanced, but not the ubiquitination of the receptor. Intriguingly, silencing of ACK1 in A498 cells sensitized the renal carcinoma cells to gefitinib, against which they are otherwise resistant. The work demonstrates that other than gene amplification, a single somatic mutation in ACK1 can result in extended protein stability enabling the oncoprotein to exert its oncogenic function in tumor progression. It also provides a rationale to target ACK1 in combination with other chemotherapeutic drugs, such as EGFR inhibitors, to potentiate therapeutic action against resistant tumors. PMID- 20359969 TI - [Inherited aplastic anemias]. AB - The inherited aplastic anaemias are a heterogeneous group of disorders characterized by bone marrow failure, frequent association with one or more somatic anomalies and increased risk of cancer. They are rare disorders, usually diagnosed at paediatric age, and have significant premature mortality. The authors report 11 cases of inherited aplastic anaemias, 8 of Fanconi's anaemia and 3 of Dyskeratosis congenita. These cases were diagnosed in the last 14 years in the Dona Estefania Hospital. PMID- 20359968 TI - Update on primary biliary cirrhosis. AB - Primary biliary cirrhosis is an autoimmune chronic liver disease characterized by progressive bile duct destruction eventually leading to cirrhosis, liver failure, and death. The autoimmune pathogenesis is supported by a plethora of experimental and clinical data, such as the presence of autoreactive T cells and serum autoantibodies. The aetiology remains unknown, although evidence suggests a role for both genetic susceptibility and environmental factors that remain to be determined. In fact, a number of chemicals and infectious agents have been proposed to induce the disease in predisposed individuals. The recent availability of several murine models will significantly help in understanding pathophysiology mechanisms. In this review, we critically summarize the most recent data on the aetiopathogenesis of primary biliary cirrhosis, discuss the latest theories and developments, and suggest directions for future research. PMID- 20359970 TI - Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy. AB - Evaluation of infants with hypoxic ischemic encephalopathy by magnetic resonance spectroscopy and imaging is useful to direct clinical care, and may assist the evaluation of candidate neuroprotective therapies. Cerebral metabolites measured by magnetic resonance spectroscopy, and visual analysis of magnetic resonance images during the first 30 days after birth accurately predict later neurological outcome and are valid biomarkers of the key physiological processes underlying brain injury in neonatal hypoxic ischemic encephalopathy. Visual assessment of magnetic resonance images may also be a suitable surrogate outcome in studies of neuroprotective therapies but current magnetic resonance methods are relatively inefficient for use in early phase, first in human infant studies of novel neuroprotective therapies. However, diffusion tensor imaging and analysis of fractional anisotropy with tract-based spatial statistics promises to be a highly efficient biomarker and surrogate outcome for rapid preliminary evaluation of promising therapies for neonatal hypoxic ischemic injury. Standardisation of scanning protocols and data analysis between different scanners is essential. PMID- 20359971 TI - Mimic hypoxia improves angiogenesis in ischaemic random flaps. AB - BACKGROUND: Hypoxia is the original signal to promote angiogenesis in ischaemic tissues. However, hypoxia-induced angiogenesis usually cannot compensate for the ischaemic injury in surgery, resulting in tissue necrosis. Mimic hypoxia may be an option to improve angiogenesis for the purpose of preventing or reducing necrosis. In this study, the authors explored the feasibility of applying hypoxic mimic--deferoxamine (DFO) to the treatment of ischaemic random skin flaps. METHODS: Ischaemic random skin flap models were developed in 18 nude mice using a cutaneous marking technique. The mice were divided into a DFO-treated group and a control group. Vascular endothelial growth factor (VEGF) protein level, vessel density and flap survival rate were evaluated on the seventh postoperative day. In vitro, both VEGF mRNA expression and protein level were investigated in endothelial cells and fibroblasts under DFO, hypoxia and normoxia conditions. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to study the impact of DFO-induced VEGF up-regulation on endothelial cell viability after severe hypoxia injury. RESULTS: The flap survival rate, vessel density and VEGF level in the DFO group are significantly higher than in the control group. In vitro, DFO-induced increase in VEGF mRNA expression translated into 2.3- and 5.8-fold increases in VEGF protein secretion in DFO conditioned media of endothelial cells and fibroblasts, respectively. The MTT assay showed that the cell viability both in the DFO group and in the VEGF group was significantly higher than in the control group. CONCLUSION: VEGF praracrine and autocrine secretion in fibroblasts and in endothelial cells play an important role in DFO-induced angiogenesis, which improves ischaemic flap survival. DFO induced VEGF autocrine secretion also protects endothelial cells from severe hypoxia injury. PMID- 20359972 TI - Evacuation of subungual haematomas using punch biopsy. PMID- 20359973 TI - Management of hypospadias cripples with two-staged Bracka's technique. AB - Patients labelled as 'hypospadias cripples' pose a challenge to reconstructive surgeons because of the complexity of the problem and limited options for reconstruction. The two-staged Bracka method is a versatile technique that is relatively easy to learn and applicable in difficult cases of salvage hypospadias. Over a period of 8 years, we applied this technique to 100 patients with hypospadias cripples who had previously undergone multiple (3-16) procedures. In the first stage, a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after release of chordee. Stage II was carried out at least 6 months after the first procedure. Meatal opening at the tip of the glans was achieved in 94 patients, straightening of the penis in 96 and proper urinary stream in 92 patients. Fistula formation occurred in nine patients. In our opinion, the two-staged Bracka technique is a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias. This technique not only creates a neourethra successfully, but also gives the penis a near-normal shape and appearance. PMID- 20359974 TI - The pedicled 'propeller' deep inferior epigastric perforator (DIEP) flap for a large abdominal wall defect. AB - The deep inferior epigastric perforator (DIEP) flap has become a popular free flap for use in breast reconstruction, providing a versatile volume of tissue with low donor site morbidity and in particular its ease of direct donor site closure. While its use in free tissue transfer has been widely reported, its use as a local pedicled flap has been more scarcely described. Limited reports include its use for hip and groin defects and in penile reconstruction. A long and robust vascular pedicle is ideal for islanded local advancement or so-called 'propeller' rotation to adjacent abdominal wall defects, with Seyhan and Borman (2008) describing such a technique for coverage of the lower abdominal wall, and we have described such a technique to aid closure of the lower abdominal wall during contralateral DIEP flap harvest. Having been presented with a large central-lower anterior abdominal wall defect, we describe a further application of the pedicled 'propeller' DIEP flap. PMID- 20359975 TI - [Membrane roughness: A relevant concept in haemodialysis]. AB - The molecular process that occurs at the interface between blood and a haemodialysis membrane determines the host response. The resulting reactions define the degree of membrane biocompatibility. These reactions are triggered by plasma protein adsorption onto the membrane and blood cell stress. Over the past decade, atomic force microscopy (AFM) has provided mechanistic insights into the molecular level of interactions that occur at the biomaterial surface. AFM provides tridimentional images produced by both changes in applied shear nanoforces and dynamic imaging through the molecular analysis of attraction and repulsion forces. The aim of the present brief review is to shortly present the technique of AFM and its emerging applications in haemodialysis, comparing hydrophilic and hydrophobic structures. Dialysis membrane roughness and protein adsorption mapping can be quantitatively estimated, since AFM resolution power is in the range of a nanometer. It is suggested that estimation of roughness and force mapping determining structure/function relationship should be proposed for the best understanding of membrane biocompatibility. PMID- 20359976 TI - A matter of degrees: advancing our understanding of acrylamide. PMID- 20359977 TI - ToxCast on target: in vitro assays and computer modeling show promise for screening chemicals. PMID- 20359978 TI - Mystery in a bottle: will the EPA require public disclosure of inert pesticide ingredients? PMID- 20359979 TI - Will ocean acidification erode the base of the food web? PMID- 20359980 TI - Brain drain? PBDEs alter development of human brain cells. PMID- 20359981 TI - Secondhand smoke exposure may alter fetal blood pressure programming. PMID- 20359982 TI - White House proposes healthy food financing initiative. PMID- 20359983 TI - Attention-worthy association: prenatal phthalate exposure and later child behavior. PMID- 20359985 TI - Chew on this: persistent organic pollutants may promote insulin resistance syndrome. PMID- 20359987 TI - [First documented cases of rheumatoid arthritis in Niger]. AB - The authors report the first eight documented cases of rheumatoid arthritis in Niger, all diagnosed during one year at the National Lamorde Hospital of Niamey. Systemic manifestations were rare. PMID- 20359988 TI - School health and environment. PMID- 20359989 TI - Who's in charge of children's environmental health at school? AB - Children spend many hours each week in and around school buildings. Their short- and long-term health outcomes and ability to learn are affected by numerous environmental factors related to the school buildings, the school grounds, the school transportation system, and the use of various products and materials in and around the school. Many school buildings are old, and they-and even newer buildings-can contain multiple environmental health hazards. While some districts self-report they have environmental health policies in place, no independent verification of these policies or their quality exists. Teachers and other staff, but not children who are more vulnerable to hazards than adults, are afforded some protections from hazards by Occupational Safety and Health Administration (OSHA) regulations, by their employment contracts, or through adult occupational health services. Major environmental problems include: indoor air quality, lighting, pests and pesticides, heavy metals and chemical management issues, renovation of occupied buildings, noise, and cleaning processes and products. No agency at the federal or state levels is charged with ensuring children's health and safety in and around school buildings. No systematic means exists for collecting data about exposures which occur in the school setting. Recommendations are made for dealing with issues of data collection, federal actions, state and local actions, and for building the capacity of the Environmental Protection Agency and the Centers for Disease Control and Prevention-designated and funded Pediatric Environmental Health Specialty Units (PEHSU) in responding to and evaluating risks to children's environmental health in schools. PMID- 20359990 TI - Failing our children: lead in U.S. school drinking water. AB - Lead is the most prevalent toxicant in U. S. school drinking water. Yet for the vast majority of schools, federal regulation for testing taps and remediating contamination is voluntary. Using school case studies, this article discusses the regulatory vacuum that leaves children unprotected from potential exposure to very high lead doses through consumption of school water. Controlling lead hazards from water fountains, coolers, and other drinking water outlets in schools requires improved sampling protocols that can capture the inherent variability of lead release from plumbing and measure both the particulate and dissolved lead present in water. There is a need to reevaluate the potential public health implications of lead-contaminated drinking water in schools. Accounting for this misunderstood and largely overlooked exposure source is necessary in order to better understand and address childhood lead poisoning in the U. S. PMID- 20359991 TI - Achieving healthy school siting and planning policies: understanding shared concerns of environmental planners, public health professionals, and educators. AB - Policy decisions regarding the quality of the physical school environment-both, school siting and school facility planning policies-are often considered through the lens of environmental planning, public health, or education policy, but rarely through all three. Environmental planners consider environmental justice issues on a local level and/or consider the regional impact of a school. Public health professionals focus on toxic exposures and populations particularly vulnerable to negative health outcomes. Educators and education policymakers emphasize investing in human capital of both students and staff. By understanding these respective angles and combining these efforts around the common goals of achieving adequacy and excellence, we can work toward a regulatory system for school facilities that recognizes children as a uniquely vulnerable population and seeks to create healthier school environments in which children can learn and adults can work. PMID- 20359992 TI - Integrated pest management policies in America's schools: is federal legislation needed? AB - America's school children are at risk of developing asthma and other respiratory illnesses as a result of exposure to hazardous pesticides. Integrated pest management (IPM) policies are being implemented in states and school districts across the country; however, the content and regulation of these policies vary. The need for standardization of such policies and a federal IPM law is the only way to ensure that children in America's schools are adequately protected from exposure to hazardous pesticides used to control pests. PMID- 20359993 TI - "We can't give up. It's too important." Health and safety stories from Canadian and U.S. schools. AB - Schools are supposed to be places where children learn and thrive; not where they, teachers, and other staff get sick. The hazards are many but recognition of those hazards is hard to come by in schools in Canada and the United States. The result can be an uphill fight for school-based organizations and unions. Representatives of four such groups, two each from Canada and the United States, discuss the hazards and their effects. They also have many-often unrecognized successes and related lessons to share. These include taking comprehensive approaches, looking for broad sweeps and entrees, using building sciences and strategies of solid information, acting with respect and with persistence, including students and parents, going for green cleaners, and using participatory methods. The representatives build on these to discuss what else needs to be done. The ideas are underpinned by the creativity, dedication, and persistence evident in their work to date. PMID- 20359994 TI - Surveillance of nail gun injuries by journeymen carpenters provides important insight into experiences of apprentices. AB - Experienced journeymen conducted detailed surveillance interviews with injured apprentice carpenters (n = 413). Nail gun injuries commonly occurred due to inadvertent discharge, ricocheting or projectile nails, and penetration of the wood surface. Framing nailers with contact trip triggers were most often involved; these triggers allow nail discharge anytime the trigger and nose piece are both depressed including following recoil of the tool after firing. Injured workers made concrete and practical suggestions for prevention. Scenarios were identified where changes in work practice, safer triggers, and thoughtful training could prevent injuries. Most injuries were not reported through workers' compensation; this was often due to perceived lack of injury severity, but also involved subtle as well as overt pressures on apprentices not to report. These case-based analyses are consistent with reports that many injuries from nail guns could be prevented with existing safer trigger mechanisms and training. Efforts should also focus on improved injury reporting. PMID- 20359995 TI - PCBs in school-persistent chemicals, persistent problems. AB - The issue of polychlorinated biphenyls (PCB) exposures resulting from occupancy of PCB-contaminated buildings is not new, but the contribution of building materials to that contamination is largely unrecognized. A rapidly emerging base of evidence shows that PCBs can be widely found in caulking and paint in masonry buildings constructed or renovated from about 1950 to the late 1970s. These materials can cause extensive PCB contamination of the building interiors and surrounding soil, and people who teach, live, or attend school in these buildings can have elevated serum PCB levels. The potential risk associated with this source of PCB exposure is not known; however, it is worth noting that the specific PCB congeners found at high levels in the building environments, and in biological samples from the occupants, include some that are suspected of being potent neurotoxins. The U. S. Environmental Protection Agency (EPA) is moving to address this issue in schools; however, the costs of remediating contaminated buildings will pose a formidable obstacle to most school districts. PMID- 20359996 TI - New Jersey's union-centered healthy schools work. AB - Healthy schools work is taking place on the state level throughout the United States. Perhaps more than in other states, New Jersey healthy schools work has been union-centered. The New Jersey Education Association (NJEA) collaborated with the New Jersey Work Environment Council (WEC) to produce educational materials and training sessions, provide technical assistance to local education associations, and pursue policy objectives. Pressure from members, personal connections among individuals with experience in health and safety coalitions, progressive union leadership, financial commitment, and a change in focus from regulatory compliance to member organizing contributed to the genesis and success of the work. Others doing healthy schools work may discover new possibilities from the New Jersey experience. PMID- 20359997 TI - Negotiating indoor air-case report on negotiation of teachers' union, school board on air contaminants. AB - School districts increasingly understand the need for an indoor air quality plan, but may have difficulty in producing a plan that all necessary parties will accept. This article provides a case study of how one Massachusetts school district, after experiencing environmental problems in an elementary school, worked with parents and unions to develop a comprehensive indoor air quality plan. PMID- 20359998 TI - "Serving two masters"--an interview with school teacher and union organizer Debra Askwith. AB - Debra Askwith is a teacher, union member, and environmental health and safety activist in the public schools of Springfield, Massachusetts. In the following interview, she talks about her experiences organizing around the right to public information as a teacher and a union member. Working with the assistance of lawyers, she has learned to maneuver in the hierarchy of city and school administrators as well as the city's department of education, finding allies and meeting resistance in a variety of places. She has worked on asbestos, mold, indoor air quality, infectious disease, and civil rights to protect all students and workers. PMID- 20359999 TI - Editorial from the "Monthly Journal of the International Association of Machinists," Vol. X, No. 4, April 1898. Upon the sinking of the battleship U.S.S. Maine. PMID- 20360002 TI - Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. AB - The formation of myelin requires a series of complex signaling events initiated by the axon to surrounding glial cells, which ultimately respond by tightly wrapping the axon with layers of specialized plasma membrane thereby allowing for saltatory conduction. Activation of the transcription factor NF-kappaB in Schwann cells has been suggested to be critical for these cells to differentiate into a myelinating phenotype; however, the mechanisms by which it is activated have yet to be elucidated. Here, we demonstrate that axonal membranes are sufficient to promote NF-kappaB activation in cultured Schwann cells and identify neuregulin 1 (NRG1), specifically the membrane-bound type III isoform, as the signal responsible for activating this transcription factor. Surprisingly, neither membrane-bound type I nor the soluble NRG1 EGF domain could activate NF-kappaB, indicating that type III induces a qualitatively unique signal. The transcriptional activity of NF-kappaB was significantly enhanced by treatment with forskolin, indicating these two signals converge for maximal activation. Both ErbB2 and -3 receptors were required for transducing the NRG1 signal, because gene deletion of ErbB3 in Schwann cells or treatment with the ErbB2 selective inhibitor, PKI-166, prevented the stimulation of NF-kappaB by axonal membranes. Finally, PKI-166 blocked the activation of the transcription factor in myelinating neuron/Schwann cell co-cultures and in vivo, in developing sciatic nerves. Taken together, these data establish NRG1 type III as the activator of NF kappaB during myelin formation. PMID- 20360003 TI - Kinetics of DNA unwinding by the RecD2 helicase from Deinococcus radiodurans. AB - RecD2 from Deinococcus radiodurans is a superfamily 1 DNA helicase that is homologous to the Escherichia coli RecD protein but functions outside the context of RecBCD enzyme. We report here on the kinetics of DNA unwinding by RecD2 under single and multiple turnover conditions. There is little unwinding of 20-bp substrates by preformed RecD2-dsDNA complexes when excess ssDNA is present to trap enzyme molecules not bound to the substrate. A shorter 12-bp substrate is unwound rapidly under single turnover conditions. The 12-bp unwinding reaction could be simulated with a mechanism in which the DNA is unwound in two kinetic steps with rate constant of k(unw) = 5.5 s(-1) and a dissociation step from partially unwound DNA of k(off) = 1.9 s(-1). These results indicate a kinetic step size of about 3-4 bp, unwinding rate of about 15-20 bp/s, and low processivity (p = 0.74). The reaction time courses with 20-bp substrates, determined under multiple turnover conditions, could be simulated with a four step mechanism and rate constant values very similar to those for the 12-bp substrate. The results indicate that the faster unwinding of a DNA substrate with a forked end versus only a 5'-terminal single-stranded extension can be accounted for by a difference in the rate of enzyme binding to the DNA substrates. Analysis of reactions done with different RecD2 concentrations indicates that the enzyme forms an inactive dimer or other oligomer at high enzyme concentrations. RecD2 oligomers can be detected by glutaraldehyde cross-linking but not by size exclusion chromatography. PMID- 20360004 TI - Scaffold proteins IRSp53 and spinophilin regulate localized Rac activation by T lymphocyte invasion and metastasis protein 1 (TIAM1). AB - The Rac exchange factor Tiam1 is involved in diverse cell functions and signaling pathways through multiple protein interactions, raising the question of how signaling and functional specificity are achieved. We have shown that Tiam1 interactions with different scaffold proteins activate different Rac-dependent pathways by recruiting specific Rac effector proteins, and reasoned that there must be regulatory mechanisms governing each interaction. Fibroblasts express at least two Tiam1-interacting proteins, insulin receptor substrate protein 53 kDa (IRSp53) and spinophilin. We used fluorescent resonance energy transfer (FRET) to measure localized Rac activation associated with IRSp53 and spinophilin complexes in individual fibroblasts to test this hypothesis. Pervanadate or platelet derived growth factor induced localized Rac activation dependent on Tiam1 and IRSp53. Forskolin or epinephrine induced localized Rac activation dependent on Tiam1 and spinophilin. In spinophilin-deficient cells, Tiam1 co-localized with IRSp53 in response to pervanadate or platelet-derived growth factor. In IRSp53 deficient cells, Tiam1 co-localized with spinophilin in response to forskolin or epinephrine. Total cellular levels of activated Rac were affected only in cells with exogenous Tiam1, and were primarily increased in the membrane fraction. Downstream effects of Rac activation were also stimulus and scaffold-specific. Cell ruffling, spreading, and cell adhesion were dependent on IRSp53, but not spinophilin. Epinephrine decreased IRSp53-dependent adhesion and increased cell migration in a Rac and spinophilin-dependent fashion. These results support the idea that Tiam1 interactions with different scaffold proteins couple distinct upstream signals to localized Rac activation and specific downstream pathways, and suggest that manipulating Tiam1-scaffold interactions can modulate Rac dependent cellular behaviors. PMID- 20360005 TI - A novel intronic peroxisome proliferator-activated receptor gamma enhancer in the uncoupling protein (UCP) 3 gene as a regulator of both UCP2 and -3 expression in adipocytes. AB - Uncoupling Proteins (UCPs) are integral ion channels residing in the inner mitochondrial membrane. UCP2 is ubiquitously expressed, while UCP3 is found primarily in muscles and adipose tissue. Although the exact molecular mechanism of action is controversial, it is generally agreed that both homologues function to facilitate mitochondrial fatty acid oxidation. UCP2 and -3 expression is activated by the peroxisome proliferator-activated receptors (PPARs), but so far no PPAR response element has been reported in the vicinity of the Ucp2 and Ucp3 genes. Using genome-wide profiling of PPARgamma occupancy in 3T3-L1 adipocytes we demonstrate that PPARgamma associates with three chromosomal regions in the vicinity of the Ucp3 locus and weakly with a site in intron 1 of the Ucp2 gene. These sites are isolated from the nearest neighboring sites by >900 kb. The most prominent PPARgamma binding site in the Ucp2 and Ucp3 loci is located in intron 1 of the Ucp3 gene and is the only site that facilitates PPARgamma transactivation of a heterologous promoter. This site furthermore transactivates the endogenous Ucp3 promoter, and using chromatin conformation capture we show that it loops out to specifically interact with the Ucp2 promoter and intron 1. Our data indicate that PPARgamma transactivation of both UCP2 and -3 is mediated through this novel enhancer in Ucp3 intron 1. PMID- 20360006 TI - Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. AB - Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). The largest of these were confirmed by quantitative PCR, which also revealed that insulin produced a similar effect, but with a smaller magnitude of response. After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. PMID- 20360007 TI - Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition. AB - Progression through mitosis requires the coordinated regulation of Cdk1 kinase activity. Activation of Cdk1 is a multistep process comprising binding of Cdk1 to cyclin B, relocation of cyclin-kinase complexes to the nucleus, activating phosphorylation of Cdk1 on Thr(161) by the Cdk-activating kinase (CAK; Cdk7 in metazoans), and removal of inhibitory Thr(14) and Tyr(15) phosphorylations. This dephosphorylation is catalyzed by the dual specific Cdc25 phosphatases, which occur in three isoforms in mammalian cells, Cdc25A, -B, and -C. We find that expression of Cdc25A leads to an accelerated G(2)/M phase transition. In Cdc25A overexpressing cells, Cdk1 exhibits high kinase activity despite being phosphorylated on Tyr(15). In addition, Tyr(15)-phosphorylated Cdk1 binds more cyclin B in Cdc25A-overexpressing cells compared with control cells. Consistent with this observation, we demonstrate that in human transformed cells, Cdc25A and Cdc25B, but not Cdc25C phosphatases have an effect on timing and efficiency of cyclin-kinase complex formation. Overexpression of Cdc25A or Cdc25B promotes earlier assembly and activation of Cdk1-cyclin B complexes, whereas repression of these phosphatases by short hairpin RNA has a reverse effect, leading to a substantial decrease in amounts of cyclin B-bound Cdk1 in G(2) and mitosis. Importantly, we find that Cdc25A overexpression leads to an activation of Cdk7 and increase in Thr(161) phosphorylation of Cdk1. In conclusion, our data suggest that complex assembly and dephosphorylation of Cdk1 at G(2)/M is tightly coupled and regulated by Cdc25 phosphatases. PMID- 20360009 TI - Recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon RME-1, Rab35/EPI64C, and an N-terminal domain. AB - Regulation of the number of Ca(2+)-activated K(+) channels at the endothelial cell surface contributes to control of the endothelium-derived hyperpolarizing factor response, although this process is poorly understood. To address the fate of plasma membrane-localized KCa2.3, we utilized an extracellular epitope-tagged channel in combination with fluorescence and biotinylation techniques in both human embryonic kidney cells and the human microvascular endothelial cell line, HMEC-1. KCa2.3 was internalized from the plasma membrane and degraded with a time constant of 18 h. Cell surface biotinylation demonstrated that KCa2.3 was rapidly endocytosed and recycled back to the plasma membrane. Consistent with recycling, expression of a dominant negative (DN) RME-1 or Rab35 as well as wild type EPI64C, the Rab35 GTPase-activating protein, resulted in accumulation of KCa2.3 in an intracellular compartment. Expression of DN RME-1, DN Rab35, or wild type EPI64C resulted in a decrease in steady-state plasma membrane expression. Knockdown of EPI64C increased cell surface expression of KCa2.3. Furthermore, the effect of EPI64C was dependent upon its GTPase-activating proteins activity. Co immunoprecipitation studies confirmed an association between KCa2.3 and both Rab35 and RME-1. In contrast to KCa2.3, KCa3.1 was rapidly endocytosed and degraded in an RME-1 and Rab35-independent manner. A series of N-terminal deletions identified a 12-amino acid region, Gly(206)-Pro(217), as being required for the rapid recycling of KCa2.3. Deletion of Gly(206)-Pro(217) had no effect on the association of KCa2.3 with Rab35 but significantly decreased the association with RME-1. These represent the first studies elucidating the mechanisms by which KCa2.3 is maintained at the plasma membrane. PMID- 20360008 TI - RecN is a cohesin-like protein that stimulates intermolecular DNA interactions in vitro. AB - The bacterial RecN protein is involved in the recombinational repair of DNA double-stranded breaks, and recN mutants are sensitive to DNA-damaging agents. Little is known about the biochemical function of RecN. Protein sequence analysis suggests that RecN is related to the SMC (structural maintenance of chromosomes) family of proteins, predicting globular N- and C-terminal domains connected by an extensive coil-coiled domain. The N- and C-domains contain the nucleotide-binding sequences Walker A and Walker B, respectively. We have purified the RecN protein from Deinococcus radiodurans and characterized its DNA-dependent and DNA independent ATPase activity. The RecN protein hydrolyzes ATP with a k(cat) of 24 min(-1), and this rate is stimulated 4-fold by duplex DNA but not by single stranded DNA. This DNA-dependent ATP turnover rate exhibits a dependence on the concentration of RecN protein, suggesting that RecN-RecN interactions are required for efficient ATP hydrolysis, and those interactions are stabilized only by duplex DNA. Finally, we show that RecN stimulates the intermolecular ligation of linear DNA molecules in the presence of DNA ligase. This DNA bridging activity is strikingly similar to that of the cohesin complex, an SMC family member, to which RecN is related. PMID- 20360010 TI - Phospho-regulated ACAP4-Ezrin interaction is essential for histamine-stimulated parietal cell secretion. AB - The ezrin-radixin-moesin proteins provide a regulated linkage between membrane proteins and the cortical cytoskeleton and also participate in signal transduction pathways. Ezrin is localized to the apical membrane of parietal cells and couples the protein kinase A activation cascade to the regulated HCl secretion. Our recent proteomic study revealed a protein complex of ezrin-ACAP4 ARF6 essential for volatile membrane remodeling (Fang, Z., Miao, Y., Ding, X., Deng, H., Liu, S., Wang, F., Zhou, R., Watson, C., Fu, C., Hu, Q., Lillard, J. W., Jr., Powell, M., Chen, Y., Forte, J. G., and Yao, X. (2006) Mol. Cell Proteomics 5, 1437-1449). However, knowledge of whether ACAP4 physically interacts with ezrin and how their interaction is integrated into membrane cytoskeletal remodeling has remained elusive. Here we provide the first evidence that ezrin interacts with ACAP4 in a protein kinase A-mediated phosphorylation dependent manner through the N-terminal 400 amino acids of ACAP4. ACAP4 locates in the cytoplasmic membrane in resting parietal cells but translocates to the apical plasma membrane upon histamine stimulation. ACAP4 was precipitated with ezrin from secreting but not resting parietal cell lysates, suggesting a phospho regulated interaction. Indeed, this interaction is abolished by phosphatase treatment and validated by an in vitro reconstitution assay using phospho mimicking ezrin(S66D). Importantly, ezrin specifies the apical distribution of ACAP4 in secreting parietal cells because either suppression of ezrin or overexpression of non-phosphorylatable ezrin prevents the apical localization of ACAP4. In addition, overexpressing GTPase-activating protein-deficient ACAP4 results in an inhibition of apical membrane-cytoskeletal remodeling and gastric acid secretion. Taken together, these results define a novel molecular mechanism linking ACAP4-ezrin interaction to polarized epithelial secretion. PMID- 20360011 TI - Efficient light harvesting by photosystem II requires an optimized protein packing density in Grana thylakoids. AB - A recently developed technique for dilution of the naturally high protein packing density in isolated grana membranes was applied to study the dependence of the light harvesting efficiency of photosystem (PS) II on macromolecular crowding. Slight dilution of the protein packing from 80% area fraction to the value found in intact grana thylakoids (70%) leads to an improved functionality of PSII (increased antenna size, enhanced connectivity between reaction centers). Further dilution induces a functional disconnection of light-harvesting complex (LHC) II from PSII. It is concluded that efficient light harvesting by PSII requires an optimal protein packing density in grana membranes that is close to 70%. We hypothesize that the decreased efficiency in overcrowded isolated grana thylakoids is caused by excited state quenching in LHCII, which has previously been correlated with neoxanthin distortion. Resonance Raman spectroscopy confirms this increase in neoxanthin distortion in overcrowded grana as compared with intact thylakoids. Furthermore, analysis of the changes in the antenna size in highly diluted membranes indicates a lipid-induced dissociation of up to two trimeric LHCII from PSII, leaving one trimer connected. This observation supports a hierarchy of LHCII-binding sites on PSII. PMID- 20360012 TI - Sympathetic activity in chronic kidney disease patients is related to left ventricular mass despite antihypertensive treatment. AB - BACKGROUND: Chronic kidney disease (CKD) patients often have sympathetic hyperactivity, which contributes to the pathogenesis of hypertension and cardiovascular organ damage. Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and angiotensin II receptor blockers (ARB) reduce sympathetic hyperactivity. Ideally, treatment should eliminate the relation between sympathetic activity and organ damage. The aim of the present study is firstly to compare left ventricular mass (LVM) of CKD patients using chronic ACEi or an ARB with LVM of controls. Secondly, we determine whether previously found muscle sympathetic nerve activity (MSNA) and arterial blood pressure during follow-up are predictive for the presence of increased LVM. Methods. We restudied 20 CKD patients and 30 healthy volunteers matched for age. Sympathetic nerve activity was quantified by the microneurography (MSNA). Arterial blood pressure was the mean of office blood pressure measurements. LVM was quantified by magnetic resonance imaging (MRI) without contrast. RESULTS: The period between MSNA and MRI measurements was 9 +/- 3 years. All patients were treated according to guidelines with an ACEi or an ARB. In CKD patients, mean systolic and diastolic arterial pressure were 129 +/- 10 and 84 +/- 5 mmHg, respectively, during follow up. In patients, as compared to controls, LVM was 93 +/- 16 versus 76 +/- 18 g, LVM index 30 +/- 5 versus 24 +/- 4 g/m(2.7) and mean wall thickness 11 +/- 2 versus 9.0 +/- 1 mm (all P < 0.01). Moreover, MSNA was related to LVM (r = 0.65, P < 0.002), LVM index (r = 0.46, P < 0.03) and LV mean wall thickness (r = 0.84, P < 0.001). Conclusions. In conclusion, the present study demonstrates that measures of LVM in CKD patients are greater than in healthy controls, despite a well-controlled blood pressure in the patients. Moreover, there is a positive relationship between these measures of LVM and MSNA, assessed years before, despite a standard antihypertensive treatment. These results support the notion that additional sympatholytic therapy could be beneficial. PMID- 20360013 TI - A simple approach for assessing equilibrated Kt/V beta 2-M on a routine basis. AB - BACKGROUND: Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods. METHODS: An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula. RESULTS: Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26). CONCLUSIONS: The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required. PMID- 20360014 TI - Systematic differences among patients initiated on home haemodialysis and peritoneal dialysis: the fallacy of potential competition. AB - BACKGROUND: The adoption of home-based dialysis therapies is growing internationally. There is a possibility that competition for patients may exist between peritoneal dialysis (PD) and home haemodialysis (HHD) for their respective growth. METHODS: Clinical demographics of patients initiating PD and HHD from 2004 to 2008 in our centre were abstracted using institutional electronic records. We compared clinical demographics, laboratory data and process of care to describe potential factors leading to patients choosing home based dialysis therapies. RESULTS: Between 2004 and 2008, 236 patients initiated home dialysis therapy in our centre: 153 patients to PD and 83 patients to HHD. PD and HHD patients differed in age (PD 62 +/- 16 vs HHD 46 +/- 13 years; P < 0.001) and gender distribution (PD 57 vs HHD 70% male; P = 0.05). A higher proportion of PD patients had diabetes and hypertension as the primary cause of their end-stage renal disease (ESRD). In contrast, there were more patients with glomerulonephritis among the HHD cohort. Cardiovascular and peripheral vascular diseases were more common among patients on PD. HHD patients had longer ESRD vintage (PD 0.34 +/- 0.69 and HHD 4.8 +/- 6.8 years on therapy; P = 0.002). The proportion of patients receiving chronic kidney disease care was higher among PD starters (PD 86 vs HHD 65%; P < 0.001). Sixteen percent of PD patients and 9% of HHD patients initiated their home-based renal replacement therapy after an acute hospitalization without prior modality education. CONCLUSION: There is a systematic difference between patients initiated on PD and HHD. Our data reaffirm that modality selection is a complex process. Patients on the two home therapies differ demographically and arrive through different routes. This finding suggests that the two home-based modalities are not in competition. PMID- 20360015 TI - Kidney allocation: where utility and fairness meet. PMID- 20360016 TI - The structure of parental involvement and relations to disease management for youth with type 1 diabetes. AB - OBJECTIVE: To test structural models of parental involvement in type 1 diabetes and to examine associations of parental involvement with adherence and metabolic control. METHODS: Two hundred and fifty-two young adolescents (10-14 years) completed reports of adherence and parents' involvement: acceptance, independence encouragement, communication, general and diabetes-specific monitoring, frequency of help, and intrusive support. HbA(1c) values came from medical records. RESULTS: A model of relationship quality, behavioral involvement, and monitoring as three separate yet interrelated factors best fit the data. Higher reports of mothers' and fathers' monitoring and fathers' relationship quality uniquely related to better adherence, whereas higher reports of fathers' behavioral involvement uniquely related to poorer adherence. Higher reports of paternal monitoring were related to lower HbA(1c). CONCLUSIONS: Adolescent perceptions of components of parental involvement are interrelated, yet separate constructs for both mothers and fathers. Parental monitoring was an important predictor of management of type 1 diabetes during adolescence. PMID- 20360017 TI - Relationship between school absenteeism and depressive symptoms among adolescents with juvenile fibromyalgia. AB - OBJECTIVE: To describe school absences in adolescents with Juvenile Primary Fibromyalgia Syndrome (JPFS) and examine the relationship between school absenteeism, pain, psychiatric symptoms, and maternal pain history. METHODS: Adolescents with JPFS (N = 102; mean age 14.96 years) completed measures of pain and depressive symptoms, and completed a psychiatric interview. Parents provided information about the adolescents' school absences, type of schooling, and parental pain history. School attendance reports were obtained directly from schools. RESULTS: Over 12% of adolescents with JPFS were homeschooled. Those enrolled in regular school missed 2.9 days per month on average, with one-third of participants missing more than 3 days per month. Pain and maternal pain history were not related to school absenteeism. However, depressive symptoms were significantly associated with school absences. CONCLUSION: Many adolescents with JPFS experience difficulties with regular school attendance. Long-term risks associated with school absenteeism and the importance of addressing psychological factors are discussed. PMID- 20360018 TI - The HEAT repeat protein ILITYHIA is required for plant immunity. AB - Plant innate immunity is mediated in part by resistance (R) proteins that detect pathogens and mount a robust defense response to fight against infection. We previously characterized proteins in the MOS4-associated complex (MAC) that function in the regulation of plant immune responses downstream of the autoactivated R protein snc1. The MAC is a highly conserved spliceosome associated complex homologous to the nineteen complex (NTC) in yeast and human. The availability of proteomics data sets in these organisms allowed us to systematically test the biological function of additional putative MAC proteins based on protein sequence homology and reverse genetics. In this study, we investigate the function of the GENERAL CONTROL NONDEREPRESSIBLE1 (GCN1) homolog in Arabidopsis. GCN1 was previously isolated as a novel component of the NTC in one proteomics study of the human spliceosome. We identified a single GCN1 homolog in Arabidopsis and partially characterized its function using available T DNA insertion mutants. This locus, previously named ILITYHIA (ILA), is required for non-host and basal resistance against Pseudomonas syringae as well as resistance conditioned by specific nucleotide binding, leucine-rich repeat (NB LRR) R proteins. Furthermore, ILA is required for systemic acquired resistance (SAR). Previous proteomic identification of MAC components in Arabidopsis did not identify ILA, and epistasis analysis between snc1 and ila revealed that ILA does not function in snc1-mediated resistance. Overall, our results show that ILA functions in immunity against bacterial infection. PMID- 20360019 TI - Overexpressing a putative aquaporin gene from wheat, TaNIP, enhances salt tolerance in transgenic Arabidopsis. AB - High soil salinity is a major abiotic stress in plant agriculture worldwide. Here, we report the characterization of a novel aquaporin gene TaNIP (Triticum asetivum L. nodulin 26-like intrinsic protein), which was involved in salt tolerance pathways in plants. TaNIP was identified and cloned through the gene chip expression analysis of a salt-tolerant wheat mutant RH8706-49 under salt stress. Quantitative reverse transcription-PCR (Q-RT-PCR) was used to detect TaNIP expression under salt, drought, cold and ABA treatment. The overexpression of TaNIP in transgenic Arabidopsis produced higher salt tolerance than wild-type plants. Localization analysis showed that TaNIP proteins tagged with green fluorescent protein (GFP) were localized to the cell plasma membrane. Under salt stress treatment, TaNIP-overexpressing Arabidopsis accumulated higher K(+), Ca(2+) and proline contents and lower Na(+) level than the wild-type plants. The overexpression of TaNIP in transgenic Arabidopsis also up-regulated the expression of a number of stress-associated genes. Our results suggest that TaNIP plays an important role in salt tolerance in Arabidopsis and can also enhance plants' tolerance to other abiotic stresses. PMID- 20360020 TI - Two coupled components of the mitogen-activated protein kinase cascade MdMPK1 and MdMKK1 from apple function in ABA signal transduction. AB - Plant mitogen-activated protein kinase (MAPK) cascades are involved in a range of biotic and abiotic stress responses, but many members of the MAPK family involved in signal transduction of the stress-related hormone ABA remain to be identified and how they regulate ABA signaling is still unclear. Here we characterized biochemically an apple MAPK signaling cascade MdMKK1-MdMPK1, which is transiently activated by ABA. Expression of MdMKK1 or MdMPK1 in the reference plant Arabidopsis (Arabidopsis thaliana) confers ABA hypersensitivity in both seed germination and seedling growth, showing that MdMKK1 and MdMPK1 are positively involved in ABA signaling. Expression of MdMKK1 or MdMPK1 up-regulates expression of several ABA-responsive transcription factor-encoding genes including ABI5. Furthermore, MdMPK1 phosphorylates the Arabidopsis ABI5 protein through the unique residue Ser314, showing that ABI5 is a potential direct downstream component of MAPK in ABA signaling. These findings indicate that the apple MdMKK1 MdMPK1-coupled signaling cascade may function in ABA signaling by regulating both expression and the phosphorylation status of the important ABA signaling component ABI5 or ABI5-like transcription factors. PMID- 20360021 TI - A rapid, direct observation method to isolate mutants with defects in starch grain morphology in rice. AB - Starch forms transparent grains, referred to as starch grains (SGs), in amyloplasts. Despite the simple glucose polymer composition of starch, SGs exhibit different morphologies depending on plant species, especially in the endosperm of the Poaceae family. This study reports a novel method for preparing thin sections of endosperm without chemical fixation or resin embedding that allowed us to visualize subcellular SGs clearly. Using this method, we observed the SG morphologies of >5,000 mutagenized rice seeds and were able to isolate mutants in which SGs were morphologically altered. In five mutants, named ssg (substandard starch grain), increased numbers of small SGs (ssg1-ssg3), enlarged SGs (ssg4) and abnormal interior structures of SGs (ssg5) were observed. Amylopectin chain length distribution analysis and identification of the mutated gene suggested a possible allelic relationship between ssg1, ssg2, ssg3 and the previously isolated amylose-extender (ae) mutants, while ssg4 and ssg5 seemed to be novel mutants. Compared with conventional observation methods, the methods developed here are more effective for obtaining fine images of subcellular SGs and are suitable for the observation of a large number of samples. PMID- 20360022 TI - Letter to the editor: Stability of Random Forest importance measures. AB - The goal of this article (letter to the editor) is to emphasize the value of exploring ranking stability when using the importance measures, mean decrease accuracy (MDA) and mean decrease Gini (MDG), provided by Random Forest. We illustrate with a real and a simulated example that ranks based on the MDA are unstable to small perturbations of the dataset and ranks based on the MDG provide more robust results. PMID- 20360023 TI - Changes in intracellular Na+ in heart failure following SERCA knockout--more of a solution or more of a problem? PMID- 20360024 TI - Swing those arms: automatic movement controlled by the cerebral cortex. PMID- 20360025 TI - An encounter of the third kind without the usual suspects: coherent activation of asynchronous transmitter release independent of presynaptic excitation. PMID- 20360026 TI - The epithelial glycine transporter GLYT1: protecting the gut from inflammation. PMID- 20360027 TI - Tangential torque tunes touch. PMID- 20360028 TI - Metaboreflex control of the heart. PMID- 20360029 TI - Aldosterone renin ratio in patients with resistant hypertension. PMID- 20360030 TI - An unusual cause of dyspepsia: oesophageal cavernous haemangioma. PMID- 20360031 TI - Health impact assessment of the 2012 London Olympic transport plans. AB - BACKGROUND: Transport is a structural determinant of health. We have assessed the potential of transport plans for the 2012 London Olympic Games to achieve the sustainability commitment of 'encouraging healthy living'. METHODS: We compared national and London-wide policies against developments described in the Transport Assessment, a public planning document, for the period of the Games and the aftermath legacy. RESULTS: National and London policies recommend modal shift in travel-more walking and cycling for health benefits, and fewer motor vehicles journeys to reduce harm and risks. For the Games, most spectators will use public transport, with low pollution and injury impacts and some are predicted to attend by cycling or walking. Redevelopment of the Olympics site after the Games will provide green areas for cycling and walking and better public transport, but road traffic is predicted to increase and noise and air pollution will persist above recommended levels. CONCLUSIONS: Transport planning for the London Olympic Games is contributing to sustainability. The impact on population health should be measured prospectively. PMID- 20360032 TI - Probing native protein structures by chemical cross-linking, mass spectrometry, and bioinformatics. AB - Chemical cross-linking of reactive groups in native proteins and protein complexes in combination with the identification of cross-linked sites by mass spectrometry has been in use for more than a decade. Recent advances in instrumentation, cross-linking protocols, and analysis software have led to a renewed interest in this technique, which promises to provide important information about native protein structure and the topology of protein complexes. In this article, we discuss the critical steps of chemical cross-linking and its implications for (structural) biology: reagent design and cross-linking protocols, separation and mass spectrometric analysis of cross-linked samples, dedicated software for data analysis, and the use of cross-linking data for computational modeling. Finally, the impact of protein cross-linking on various biological disciplines is highlighted. PMID- 20360034 TI - Comment on: Monitoring Achilles enthesitis in ankylosing spondylitis during TNF alpha antagonist therapy: an ultrasound study. PMID- 20360033 TI - Simultaneous glycan-peptide characterization using hydrophilic interaction chromatography and parallel fragmentation by CID, higher energy collisional dissociation, and electron transfer dissociation MS applied to the N-linked glycoproteome of Campylobacter jejuni. AB - Campylobacter jejuni is a gastrointestinal pathogen that is able to modify membrane and periplasmic proteins by the N-linked addition of a 7-residue glycan at the strict attachment motif (D/E)XNX(S/T). Strategies for a comprehensive analysis of the targets of glycosylation, however, are hampered by the resistance of the glycan-peptide bond to enzymatic digestion or beta-elimination and have previously concentrated on soluble glycoproteins compatible with lectin affinity and gel-based approaches. We developed strategies for enriching C. jejuni HB93-13 glycopeptides using zwitterionic hydrophilic interaction chromatography and examined novel fragmentation, including collision-induced dissociation (CID) and higher energy collisional (C-trap) dissociation (HCD) as well as CID/electron transfer dissociation (ETD) mass spectrometry. CID/HCD enabled the identification of glycan structure and peptide backbone, allowing glycopeptide identification, whereas CID/ETD enabled the elucidation of glycosylation sites by maintaining the glycan-peptide linkage. A total of 130 glycopeptides, representing 75 glycosylation sites, were identified from LC-MS/MS using zwitterionic hydrophilic interaction chromatography coupled to CID/HCD and CID/ETD. CID/HCD provided the majority of the identifications (73 sites) compared with ETD (26 sites). We also examined soluble glycoproteins by soybean agglutinin affinity and two-dimensional electrophoresis and identified a further six glycosylation sites. This study more than doubles the number of confirmed N-linked glycosylation sites in C. jejuni and is the first to utilize HCD fragmentation for glycopeptide identification with intact glycan. We also show that hydrophobic integral membrane proteins are significant targets of glycosylation in this organism. Our data demonstrate that peptide-centric approaches coupled to novel mass spectrometric fragmentation techniques may be suitable for application to eukaryotic glycoproteins for simultaneous elucidation of glycan structures and peptide sequence. PMID- 20360036 TI - Ultrasound-guided corticosteroid injection in rheumatology: accuracy or efficacy? PMID- 20360037 TI - Need for determining the incidence and prevalence of JIA in developing countries: the Indian predicament. PMID- 20360038 TI - Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis using vertebral fracture assessment. AB - OBJECTIVE: To study the prevalence and risk factors of vertebral fractures (VFs) in a large cohort of patients with RA using VF assessment (VFA). METHODS: We enrolled 172 women with RA, none of whom were taking osteoporosis medications. Patients underwent dual X-ray absorptiometry at the hip and spine and VFA, and completed a questionnaire. Radiological status was assessed by the modified Sharp erosion and narrowing score. VFA was classified using a combination of Genant semi-quantitative approach and morphometry. RESULTS: Patients had a mean (s.d.) disease duration of 8.4 (5.2) years. VFs were detected in 36% (62/172). This group of women had a statistically significant lower weight, height and lumbar spine and total hip BMD and T-scores than those without a VFA-identified VF. They also had more long-standing and severe disease and a greater consumption of corticosteroids. Stepwise regression analysis showed that the presence of VFs was independently associated with low weight and total hip T-score and long disease duration, CRP and Sharp erosion score. CONCLUSION: RA is a risk factor on its own for the development of osteoporosis and VFs and this risk increases more with low weight, disease duration and severe course of disease. These findings may suggest that to prevent the development of VFs, precautions should be taken immediately to suppress the disease activity and correct the weight loss in patients with RA. PMID- 20360039 TI - Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology--a genetic association study. AB - OBJECTIVES: Achilles tendon pathology is a multifactorial condition for which various risk factors, including genetic factors, have been identified. Gene transfection of two members of the TGF-beta family, TGF-beta1 and growth/differentiation factor-5 (GDF-5), have been shown to enhance tendon repair and mechanical strength within animal Achilles tendon injury models. The objective of this study was to investigate whether two functional 5' untranslated region (UTR) single nucleotide polymorphisms (SNPs), the TGFB1 rs1800469 variant and the GDF5 rs143383 variant, were associated with ATP within an Australian ('AUS') and a South African ('SA') case-control cohort. METHODS: One hundred and seventy-one subjects (58 AUS and 112 SA) with Achilles tendon pathology (ATP group) and 235 (142 AUS and 96 SA) asymptomatic control (CON group) subjects were genotyped for the selected SNPs using custom-designed Taqman assays. A chi(2) analysis or Fisher's exact test was used to analyse any differences in the genotype and allele frequencies. Significance was accepted when P < 0.05. RESULTS: There were no significant TGFB1 rs1800469 genotype (P = 0.491) or allele (P = 0.400) frequency differences between the ATP and CON groups. The TT genotype of the GDF5 rs143383 variant was significantly over-represented in the ATP group of the AUS cohort [P = 0.011; odds ratio (OR) = 2.24; 95% CI 1.21, 4.16], and when the AUS and SA cohorts were combined (P = 0.004; OR = 1.82; 95% CI 1.23, 2.74). CONCLUSIONS: In conclusion, this study suggests that individuals with a TT genotype of the functional GDF5 rs143383 variant have twice the risk of developing ATP. This finding highlights a role of GDF-5 in the pathogenesis of Achilles tendon pathology. PMID- 20360040 TI - Localized vasculitis of the gastrointestinal tract: a case series. AB - OBJECTIVE: To describe the clinical features and outcomes of patients with localized vasculitis of the gastrointestinal tract (LVGT). METHODS: Medical records of 608 patients diagnosed with vasculitis involving the intra-abdominal vasculature and/or abdominal viscera between January 1996 and December 2007 were reviewed. Only patients with histopathological confirmation or typical angiographic findings of vasculitis localized to the abdomen were included. RESULTS: We identified 18 cases with LVGT over the 12-year study period. The patients were predominantly Caucasian (89%) and female (67%) with a median age at diagnosis of 53.5 (range 17.4-83.3) years. Most of the patients presented with abdominal pain and 12 (66.6%) patients presented with an acute abdomen requiring surgical intervention. At diagnosis, the median ESR was 30.5 (range 4-77) mm/h. Autoantibody screening was generally unrevealing. Abdominal CT scan findings included: bowel wall thickening, bowel infarction and solid organ infarcts. In 14 patients, the diagnosis of vasculitis was established by abdominal angiography. Histological evidence of vasculitis was recorded in 5 (28%) patients, most commonly from gall bladder or small intestine specimens. Corticosteroid therapy was administered to 10 (56%) patients, 5 of whom also received other immunosuppressive agents. Median duration of follow-up was 10.5 (range 2-156) months. No evidence of vasculitis outside the abdomen was observed during follow up. Seven (39%) patients died during the follow-up period. Survival of the patient cohort (compared with an age-matched US white population) was significantly reduced (P < 0.001). CONCLUSION: LVGT is an uncommon form of vasculitis that can be associated with significant morbidity and mortality. PMID- 20360041 TI - Evaluation of the treatment effect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: results of a meta-analysis. AB - OBJECTIVES: To assess the treatment effect of NSAIDs and TNF blockers in AS according to different domains of interest. METHODS: A systematic literature research was performed in electronic databases up to October 2009. All randomized controlled trials (RCTs) reporting the efficacy (on pain and/or physical function and/or acute-phase reactants) of NSAIDs/anti-TNF vs placebo in AS were selected. Pooled effect sizes were calculated by meta-analysis, using fixed or random effect models. RESULTS: Optimal data to calculate the effect size were available in 8 out of the 240 selected RCTs evaluating anti-TNF and 5 of the 135 evaluating NSAIDs. For the domains pain, physical function and patient's global assessment, the treatment effect was large or medium for both TNF blockers and NSAIDs. For the domain acute-phase reactants, the effect of TNF blockers was medium [standardized mean difference (SMD) (95% CI) -0.56 (-0.70, -0.42)], whereas NSAIDs had no significant effect on acute-phase reactants {SMD [95% odds ratio (OR)] -0.09 (-0.34, 0.16)}. Finally for the domain mobility, the effect of both TNF blockers and NSAIDs was small and not significant. CONCLUSION: This study suggests that the treatment effect of NSAIDs and anti-TNF are both of relevant magnitude considering the main patient-reported outcomes but with a trend in favour of anti-TNF despite the fact that such drugs are given on top of NSAIDs in refractory patients. Moreover, a statistically significant difference was observed for the domain 'acute-phase reactants' confirming the specificity of such drug category. PMID- 20360042 TI - Distinct bacterial colonization patterns of Escherichia coli subtypes associate with rheumatoid factor status in early inflammatory arthritis. AB - OBJECTIVES: The aetiology of RA is unknown; however, bacterial exposure, particularly to Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae, has been linked to disease pathogenesis. The strongest association was observed for RF(+) RA. We compare colonization patterns of these bacteria, and the anti bacterial antibody levels in early onset RF(+) and RF(-) inflammatory arthritis. METHODS: Bacteria isolated from stool and urine of early-stage RF(+) and RF(-) patients recruited to the Early Arthritis Registry were biochemically identified and genotyped. IgM and IgA anti-bacterial and RF antibodies were assessed by ELISA. RESULTS: Differences in the types of colonizing pathogenic E. coli were identified. RF(+) patients were more commonly colonized with phylogenetic Group D E. coli, whereas RF(-) patients were more commonly colonized with phylogenetic Group B2 E. coli and these individuals also had lower joint scores and inflammatory markers yet higher IgA anti-E. coli antibody responses. CONCLUSIONS: These studies link the type of colonizing bacteria in the gut and urine with the immune response (anti-bacterial and RF) in early-onset inflammatory arthritis and provide evidence for a role of the host-pathogen response in the aetiology of RF. PMID- 20360043 TI - Dynamic evolution of megasatellites in yeasts. AB - Megasatellites are a new family of long tandem repeats, recently discovered in the yeast Candida glabrata. Compared to shorter tandem repeats, such as minisatellites, megasatellite motifs range in size from 135 to more than 300 bp, and allow calculation of evolutionary distances between individual motifs. Using divergence based on nucleotide substitutions among similar motifs, we determined the smallest distance between two motifs, allowing their subsequent clustering. Motifs belonging to the same cluster are recurrently found in different megasatellites located on different chromosomes, showing transfer of genetic information between megasatellites. In comparison, evolution of the few similar tandem repeats in Saccharomyces cerevisiae FLO genes mainly involves subtelomeric homologous recombination. We estimated selective constraints acting on megasatellite motifs and their host genes, and found that motifs are under strong purifying selection. Surprisingly, motifs inserted within pseudogenes are also under purifying selection, whereas the pseudogenes themselves evolve neutrally. We propose that megasatellite motifs propagate by a combination of three different molecular mechanisms: (i) gene duplication, (ii) ectopic homologous recombination and (iii) transfer of motifs from one megasatellite to another one. These mechanisms actively cooperate to create new megasatellites, that may play an important role in the adaptation of Candida glabrata to its human host. PMID- 20360044 TI - Cell-type-specific long-range looping interactions identify distant regulatory elements of the CFTR gene. AB - Identification of regulatory elements and their target genes is complicated by the fact that regulatory elements can act over large genomic distances. Identification of long-range acting elements is particularly important in the case of disease genes as mutations in these elements can result in human disease. It is becoming increasingly clear that long-range control of gene expression is facilitated by chromatin looping interactions. These interactions can be detected by chromosome conformation capture (3C). Here, we employed 3C as a discovery tool for identification of long-range regulatory elements that control the cystic fibrosis transmembrane conductance regulator gene, CFTR. We identified four elements in a 460-kb region around the locus that loop specifically to the CFTR promoter exclusively in CFTR expressing cells. The elements are located 20 and 80 kb upstream; and 109 and 203 kb downstream of the CFTR promoter. These elements contain DNase I hypersensitive sites and histone modification patterns characteristic of enhancers. The elements also interact with each other and the latter two activate the CFTR promoter synergistically in reporter assays. Our results reveal novel long-range acting elements that control expression of CFTR and suggest that 3C-based approaches can be used for discovery of novel regulatory elements. PMID- 20360045 TI - Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence. AB - FoxM1 is a member of the Forkhead family of transcription factors and is implicated in inducing cell proliferation and some forms of tumorigenesis. It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence. The affinity of the isolated FoxM1 DNA-binding domain for this site is in the micromolar range, lower than observed for other Forkhead proteins. To explain these FoxM1 features, we determined the crystal structure of its DNA-binding domain in complex with a tandem recognition sequence. FoxM1 adopts the winged-helix fold, typical of the Forkhead family. Neither 'wing' of the fold however, makes significant contacts with the DNA, while the second, C-terminal, wing adopts an unusual ordered conformation across the back of the molecule. The lack of standard DNA-'wing' interactions may be a reason for FoxM1's relatively low affinity. The role of the 'wings' is possibly undertaken by other FoxM1 regions outside the DBD, that could interact with the target DNA directly or mediate interactions with other binding partners. Finally, we were unable to show a clear preference for tandem consensus site recognition in DNA-binding, transcription activation or bioinformatics analysis; FoxM1's moniker, 'Trident', is not supported by our data. PMID- 20360046 TI - Global and local depletion of ternary complex limits translational elongation. AB - The translation of genetic information according to the sequence of the mRNA template occurs with high accuracy and fidelity. Critical events in each single step of translation are selection of transfer RNA (tRNA), codon reading and tRNA regeneration for a new cycle. We developed a model that accurately describes the dynamics of single elongation steps, thus providing a systematic insight into the sensitivity of the mRNA translation rate to dynamic environmental conditions. Alterations in the concentration of the aminoacylated tRNA can transiently stall the ribosomes during translation which results, as suggested by the model, in two outcomes: either stress-induced change in the tRNA availability triggers the premature termination of the translation and ribosomal dissociation, or extensive demand for one tRNA species results in a competition between frameshift to an aberrant open-reading frame and ribosomal drop-off. Using the bacterial Escherichia coli system, we experimentally draw parallels between these two possible mechanisms. PMID- 20360047 TI - Non-canonical DNA transcription enzymes and the conservation of two-barrel RNA polymerases. AB - DNA transcription depends on multimeric RNA polymerases that are exceptionally conserved in all cellular organisms, with an active site region of >500 amino acids mainly harboured by their Rpb1 and Rpb2 subunits. Together with the distantly related eukaryotic RNA-dependent polymerases involved in gene silencing, they form a monophyletic family of ribonucleotide polymerases with a similarly organized active site region based on two double-Psi barrels. Recent viral and phage genome sequencing have added a surprising variety of putative nucleotide polymerases to this protein family. These proteins have highly divergent subunit composition and amino acid sequences, but always contain eight invariant amino acids forming a universally conserved catalytic site shared by all members of the two-barrel protein family. Moreover, the highly conserved 'funnel' and 'switch 2' components of the active site region are shared by all putative DNA-dependent RNA polymerases and may thus determine their capacity to transcribe double-stranded DNA templates. PMID- 20360048 TI - The siRNA sequence and guide strand overhangs are determinants of in vivo duration of silencing. AB - The use of short interfering RNAs (siRNA) in animals for target validation or as potential therapeutics is hindered by the short physical half-life when delivered as unencapsulated material and in turn the short active half-life of siRNAs in vivo. Here we demonstrate that the character of the two 3'-overhang nucleotides of the guide strand of siRNAs is a determinant of the duration of silencing by siRNAs both in vivo and in tissue culture cells. We demonstrate that deoxyribonucleotides in the guide strand overhang of siRNAs have a negative impact on maintenance of both the in vitro and in vivo activity of siRNAs over time. Overhangs that contain ribonucleotides or 2'-O-methyl modified nucleotides do not demonstrate this same impairment. We also demonstrate that the sequence of an siRNA is a determinant of the duration of silencing of siRNAs directed against the same target even when those siRNAs have equivalent activities in vitro. Our experiments have determined that a measurable duration parameter exists, distinct from both maximum silencing ability and the potency of siRNAs. Our findings provide information on incorporating chemically modified nucleotides into siRNAs for potent, durable therapeutics and also inform on methods used to select siRNAs for therapeutic and research purposes. PMID- 20360051 TI - Remote memory deficits in transient epileptic amnesia. AB - Transient epileptic amnesia is a form of temporal lobe epilepsy in which sufferers often complain of irretrievable loss of remote memories. We used a broad range of memory tests to clarify the extent and nature of the remote memory deficits in patients with transient epileptic amnesia. Performance on standard tests of anterograde memory was normal. In contrast, there was a severe impairment of memory for autobiographical events extending across the entire lifespan, providing evidence for the occurrence of 'focal retrograde amnesia' in transient epileptic amnesia. There was a milder impairment of personal semantic memory, most pronounced for midlife years. There were limited deficits of public semantic memory for recent decades. These results may reflect subtle structural pathology in the medial temporal lobes or the effects of the propagation of epileptiform activity through the network of brain regions responsible for long term memory, or a combination of these two mechanisms. PMID- 20360050 TI - Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology. AB - Anti-amyloid-beta immunization leads to amyloid clearance in patients with Alzheimer's disease, but the effect of vaccination on amyloid-beta-induced neuronal pathology has not been quantitatively examined. The objectives of this study were to address the effects of anti-amyloid-beta active immunization on neurite trajectories and the pathological hallmarks of Alzheimer's disease in the human hippocampus. Hippocampal sections from five patients with Alzheimer's disease enrolled in the AN1792 Phase 2a trial were compared with those from 13 non-immunized Braak-stage and age-matched patients with Alzheimer's disease, and eight age-matched non-demented controls. Analyses included neurite curvature ratio as a quantitative measure of neuritic abnormalities, amyloid and tau loads, and a quantitative characterization of plaque-associated neuritic dystrophy and astrocytosis. Amyloid load and density of dense-core plaques were decreased in the immunized group compared to non-immunized patients (P < 0.01 and P < 0.001, respectively). The curvature ratio in non-immunized patients with Alzheimer's disease was elevated compared to non-demented controls (P < 0.0001). In immunized patients, however, the curvature ratio was normalized when compared to non immunized patients (P < 0.0001), and not different from non-demented controls. In the non-immunized patients, neurites close to dense-core plaques (within 50 microm) were more abnormal than those far from plaques (i.e. beyond 50 microm) (P < 0.0001). By contrast, in the immunized group neurites close to and far from the remaining dense-core plaques did not differ, and both were straighter compared to the non-immunized patients (P < 0.0001). Compared to non-immunized patients, dense-core plaques remaining after immunization had similar degree of astrocytosis (P = 0.6060), more embedded dystrophic neurites (P < 0.0001) and were more likely to have mitochondrial accumulation (P < 0.001). In addition, there was a significant decrease in the density of paired helical filament-1 positive neurons in the immunized group as compared to the non-immunized (P < 0.05), but not in the density of Alz50 or thioflavin-S positive tangles, suggesting a modest effect of anti-amyloid-beta immunization on tangle pathology. Clearance of amyloid plaques upon immunization with AN1792 effectively improves a morphological measure of neurite abnormality in the hippocampus. This improvement is not just attributable to the decrease in plaque load, but also occurs within the halo of the remaining dense-core plaques. However, these remaining plaques still retain some of their toxic potential. Anti-amyloid-beta immunization might also ameliorate the hippocampal tau pathology through a decrease in tau phosphorylation. These data agree with preclinical animal studies and further demonstrate that human anti-amyloid-beta immunization does not merely clear amyloid from the Alzheimer's disease brain, but reduces some of the neuronal alterations that characterize Alzheimer's disease. PMID- 20360052 TI - Functional gait assessment: concurrent, discriminative, and predictive validity in community-dwelling older adults. AB - BACKGROUND: The Functional Gait Assessment (FGA) is a reliable and valid measure of gait-related activities. OBJECTIVE: The purpose of this study was to determine the concurrent, discriminative, and predictive validity of the FGA in community dwelling older adults. DESIGN: This was a prospective cohort study. METHODS: Thirty-five older adults aged 60 to 90 years completed the Activities-specific Balance Confidence Scale (ABC), Berg Balance Scale (BBS), Dynamic Gait Index (DGI), Timed "Up & Go" Test (TUG), and Functional Gait Assessment (FGA) during one session. Falls were tracked by having participants complete a monthly fall calendar for 6 months. Spearman correlation coefficients were used to determine concurrent validity among the ABC, BBS, TUG, DGI, and FGA. To determine the optimum scores to classify fall risk, sensitivity (Sn), specificity (Sp), and positive and negative likelihood ratios (LR+ and LR-) were calculated for the FGA in classifying fall risk based on the published criterion scores of the DGI and TUG and for the FGA, TUG, and DGI in identifying prospective falls. Receiver operator curves with area under the curve were used to determine the effectiveness of the FGA in classifying fall risk and of the DGI, TUG, and FGA in identifying prospective falls. RESULTS: The FGA correlated with the ABC (r=.053, P<.001), BBS (r=.84, P<.001), and TUG (r=-.84, P<.001). An FGA score of or=10% or improved their NYHA functional class. Overall, 25 patients (60%) were classed as responders. At 12-month follow-up, six patients (14.2%) had died and one (2.4%) patient had been transplanted. Compared with responders, non responders had higher levels of TIMP-1 (277 +/- 59 vs. 216 +/- 46 ng/mL, P = 0.001), MMP-2 (325 +/- 115 vs. 258 +/- 56 ng/mL, P = 0.02), and creatinine (1.76 +/- 0.8 vs. 1.25 +/- 0.3 mg/dL, P = 0.01). In a multivariate analysis, TIMP-1 was the only independent predictor of non-response to CRT [OR 0.97, 95% (CI 0.96 0.99) P = 0.005]. TIMP-1>or=248 ng/mL predicted non-response with 71% sensitivity and 72% specificity. CONCLUSION: TIMP-1 is an independent predictor of non response in patients treated with CRT. PMID- 20360069 TI - Onset of convective rainfall during gradual late Miocene rise of the central Andes. AB - A decrease in the ratio of 18O to 16O (delta18O) of sedimentary carbonate from the Bolivian Altiplano has been interpreted to indicate rapid surface uplift of the late Miocene Andean plateau (AP). Here we report on paleoclimate simulations of Andean surface uplift with an atmospheric general circulation model (GCM) that tracks oxygen isotopes in vapor. The GCM predicts changes in atmospheric circulation and rainfall that influence AP isotopic source and amount effects. On eastern AP slopes, summer convective precipitation increases by up to 6 millimeters per day (>500%) for plateau elevations that are greater than about 2000 meters. High precipitation rates enhance the isotope amount effect, leading to a decrease in precipitation delta18O at high elevations and an increase in delta18O lapse rate. Our results indicate that late Miocene delta18O depletion reflects initiation and intensification of convective rainfall. PMID- 20360068 TI - Systematic analysis of human protein complexes identifies chromosome segregation proteins. AB - Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells. PMID- 20360071 TI - Climate studies. 'Asilomar 2' takes small steps toward rules for geoengineering. PMID- 20360070 TI - Empowering young scientists. PMID- 20360072 TI - Ecology. Madagascar's forests get a reprieve--but for how long? PMID- 20360075 TI - Conservation biology. Ivory ban upheld. PMID- 20360067 TI - Fermi gamma-ray imaging of a radio galaxy. AB - The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating from the giant radio lobes of the radio galaxy Centaurus A. The resolved gamma ray image shows the lobes clearly separated from the central active source. In contrast to all other active galaxies detected so far in high-energy gamma-rays, the lobe flux constitutes a considerable portion (greater than one-half) of the total source emission. The gamma-ray emission from the lobes is interpreted as inverse Compton-scattered relic radiation from the cosmic microwave background, with additional contribution at higher energies from the infrared-to-optical extragalactic background light. These measurements provide gamma-ray constraints on the magnetic field and particle energy content in radio galaxy lobes, as well as a promising method to probe the cosmic relic photon fields. PMID- 20360076 TI - Conservation biology. Trade trumps science for marine species at international meeting. PMID- 20360077 TI - Physics. Thought experiment torpedoes variable-speed-of-light theories. PMID- 20360078 TI - Newsmaker interview. NOAA's Tom Karl takes on task of serving up climate to the public. Interview by Richard A. Kerr. PMID- 20360079 TI - In the shadow of Jane Goodall. PMID- 20360080 TI - Chimpanzee research today. Makoku at 0 degrees 30'N 30 degrees 24'E: chimping via GPS. PMID- 20360081 TI - Chimpanzee research today. Chimps read lips. PMID- 20360082 TI - Chimpanzee research today. A matter of life and limb. PMID- 20360083 TI - Chimpanzee research today. The spread of culture, primitive as it is. PMID- 20360084 TI - Chimpanzee research today. The Chimpanzee Genome Project's seedy origins. PMID- 20360085 TI - Chimpanzee research today. Talking chimp to chimp. PMID- 20360086 TI - Chimpanzee research today. Boxed about the ears, ape language research field is still standing. PMID- 20360087 TI - Chimpanzee research today. The inner workings of the chimpanzee brain. PMID- 20360088 TI - Chimpanzee research today. Getting intimate with the chimp mind, Japanese style. PMID- 20360090 TI - Polystyrene overestimated. PMID- 20360089 TI - Chimpanzee research today. Cutting to the bone of human origins. PMID- 20360092 TI - Consent contraindicated? PMID- 20360094 TI - Suitability of artificial nests. PMID- 20360095 TI - Environment. China's road to sustainability. PMID- 20360096 TI - Virology. A vaccine monkey wrench? PMID- 20360097 TI - Applied physics. Why thick can be slick. PMID- 20360098 TI - Geochemistry. Ocean chemistry and early animals. PMID- 20360099 TI - Geophysics. What lies beneath. PMID- 20360100 TI - Physics. Fishing antihypernuclei out of a quark-gluon soup. PMID- 20360101 TI - Molecular biology. Mixing or not mixing. PMID- 20360103 TI - Evidence for strong extragalactic magnetic fields from Fermi observations of TeV blazars. AB - Magnetic fields in galaxies are produced via the amplification of seed magnetic fields of unknown nature. The seed fields, which might exist in their initial form in the intergalactic medium, were never detected. We report a lower bound B > or = 3 x 10(-16) gauss on the strength of intergalactic magnetic fields, which stems from the nonobservation of GeV gamma-ray emission from electromagnetic cascade initiated by tera-electron volt gamma rays in intergalactic medium. The bound improves as lambdaB(-1/2) if magnetic field correlation length, lambdaB, is much smaller than a megaparsec. This lower bound constrains models for the origin of cosmic magnetic fields. PMID- 20360102 TI - A gating charge transfer center in voltage sensors. AB - Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening. PMID- 20360104 TI - Frictional characteristics of atomically thin sheets. AB - Using friction force microscopy, we compared the nanoscale frictional characteristics of atomically thin sheets of graphene, molybdenum disulfide (MoS2), niobium diselenide, and hexagonal boron nitride exfoliated onto a weakly adherent substrate (silicon oxide) to those of their bulk counterparts. Measurements down to single atomic sheets revealed that friction monotonically increased as the number of layers decreased for all four materials. Suspended graphene membranes showed the same trend, but binding the graphene strongly to a mica surface suppressed the trend. Tip-sample adhesion forces were indistinguishable for all thicknesses and substrate arrangements. Both graphene and MoS2 exhibited atomic lattice stick-slip friction, with the thinnest sheets possessing a sliding-length-dependent increase in static friction. These observations, coupled with finite element modeling, suggest that the trend arises from the thinner sheets' increased susceptibility to out-of-plane elastic deformation. The generality of the results indicates that this may be a universal characteristic of nanoscale friction for atomically thin materials weakly bound to substrates. PMID- 20360105 TI - Mantle flow drives the subsidence of oceanic plates. AB - The subsidence of the sea floor is generally considered a consequence of its passive cooling and densifying since its formation at the ridge and is therefore regarded as a function of lithospheric age only. However, the lithosphere is defined as the thermal boundary layer of mantle convection, which should thus determine its structure. We examined the evolution of the lithosphere structure and depth along trajectories representative of the underlying mantle flow. We show that along these flow lines, the sea-floor depth varies as the square root of the distance from the ridge (as given by the boundary-layer equation) along the entire plate, without any flattening. Contrary to previous models, no additional heat supply is required at the base of the lithosphere. PMID- 20360106 TI - Orchestration of floral initiation by APETALA1. AB - The MADS-domain transcription factor APETALA1 (AP1) is a key regulator of Arabidopsis flower development. To understand the molecular mechanisms underlying AP1 function, we identified its target genes during floral initiation using a combination of gene expression profiling and genome-wide binding studies. Many of its targets encode transcriptional regulators, including known floral repressors. The latter genes are down-regulated by AP1, suggesting that it initiates floral development by abrogating the inhibitory effects of these genes. Although AP1 acts predominantly as a transcriptional repressor during the earliest stages of flower development, at more advanced stages it also activates regulatory genes required for floral organ formation, indicating a dynamic mode of action. Our results further imply that AP1 orchestrates floral initiation by integrating growth, patterning, and hormonal pathways. PMID- 20360107 TI - Maize tumors caused by Ustilago maydis require organ-specific genes in host and pathogen. AB - Infection of maize by corn smut (Ustilago maydis) provides an agronomically important model of biotrophic host-pathogen interactions. After penetration of the maize epidermis, fungal colonization of host tissue induces tumor formation on all aerial maize organs. We hypothesized that transformation of different primordia into plant tumors would require organ-specific gene expression by both host and pathogen and documented these differences by transcriptome profiling. Phenotypic screening of U. maydis mutants deleted for genes encoding secreted proteins and maize mutants with organ-specific defects confirmed organ-restricted tumorigenesis. This is the foundation for exploring how individual pathogen effectors, deployed in an organ-specific pattern, interact with host factors to reprogram normal ontogeny into a tumor pathway. PMID- 20360108 TI - Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. AB - Semiconservative DNA replication ensures the faithful duplication of genetic information during cell divisions. However, how epigenetic information carried by histone modifications propagates through mitotic divisions remains elusive. To address this question, the DNA replication-dependent nucleosome partition pattern must be clarified. Here, we report significant amounts of H3.3-H4 tetramers split in vivo, whereas most H3.1-H4 tetramers remained intact. Inhibiting DNA replication-dependent deposition greatly reduced the level of splitting events, which suggests that (i) the replication-independent H3.3 deposition pathway proceeds largely by cooperatively incorporating two new H3.3-H4 dimers and (ii) the majority of splitting events occurred during replication-dependent deposition. Our results support the idea that "silent" histone modifications within large heterochromatic regions are maintained by copying modifications from neighboring preexisting histones without the need for H3-H4 splitting events. PMID- 20360109 TI - Dynamic regulation of archaeal proteasome gate opening as studied by TROSY NMR. AB - The proteasome catalyzes the majority of protein degradation in the cell and plays an integral role in cellular homeostasis. Control over proteolysis by the 20S core-particle (CP) proteasome is achieved by gated access of substrate; thus, an understanding of the molecular mechanism by which these gates regulate substrate entry is critical. We used methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy to show that the amino-terminal residues that compose the gates of the alpha subunits of the Thermoplasma acidophilum proteasome are highly dynamic over a broad spectrum of time scales and that gating termini are in conformations that extend either well inside (closed gate) or outside (open gate) of the antechamber. Interconversion between these conformers on a time scale of seconds leads to a dynamic regulation of 20S CP proteolysis activity. PMID- 20360110 TI - Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. AB - Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV based vector development. PMID- 20360113 TI - The pretravel visit: a 'teaching moment'. PMID- 20360111 TI - Synchrony of thalamocortical inputs maximizes cortical reliability. AB - Thalamic inputs strongly drive neurons in the primary visual cortex, even though these neurons constitute only approximately 5% of the synapses on layer 4 spiny stellate simple cells. We modeled the feedforward excitatory and inhibitory inputs to these cells based on in vivo recordings in cats, and we found that the reliability of spike transmission increased steeply between 20 and 40 synchronous thalamic inputs in a time window of 5 milliseconds, when the reliability per spike was most energetically efficient. The optimal range of synchronous inputs was influenced by the balance of background excitation and inhibition in the cortex, which could gate the flow of information into the cortex. Ensuring reliable transmission by spike synchrony in small populations of neurons may be a general principle of cortical function. PMID- 20360114 TI - Giant nodules on the hands. PMID- 20360115 TI - When should serum amylase and lipase levels be repeated in a patient with acute pancreatitis? PMID- 20360116 TI - Bony bridge of a bifid rib. PMID- 20360117 TI - Breaking the cycle of medication overuse headache. AB - When patients who have frequent, disabling migraines take medications to relieve their symptoms, they run the risk that the attacks will increase in frequency to daily or near-daily as a rebound effect comes into play. This pattern, called medication overuse headache, is more likely to happen with butalbital and opioids than with migraine-specific drugs, as partial responses lead to recurrence, repeat dosing, and, eventually, overuse. Breaking the cycle involves weaning the patient from the overused medications, setting up a preventive regimen, and setting strict limits on the use of medications to relieve acute symptoms. PMID- 20360118 TI - Risks of travel, benefits of a specialist consult. AB - If patients are planning to travel to developing countries, their primary care physicians can counsel them on various medical risks, especially traveler's diarrhea, and offer to update their immunizations. However, travelers to areas where there is a risk of malaria, yellow fever, or other tropical diseases should be referred to a specialist. PMID- 20360119 TI - Vaccine update 2010: keeping up with the changes. AB - A number of new vaccines have been approved in recent years, and existing vaccines have been extended to new groups. We summarize the additions and changes over the past 3 years. PMID- 20360120 TI - The Courvoisier sign. PMID- 20360121 TI - New tools for detecting occult monoclonal gammopathy, a cause of secondary osteoporosis. AB - Most patients with multiple myeloma or other monoclonal gammopathies present with anemia, hypercalcemia, or renal insufficiency. However, osteoporosis may be the first sign. Measuring the concentration and ratio of free light chains in the serum can help detect monoclonal gammopathy and help to differentiate myeloma related bone loss from other secondary forms of osteoporosis. PMID- 20360122 TI - Being rational about (im)precision: a statement from the Biochemistry Subcommittee of the Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the definition of myocardial infarction. PMID- 20360123 TI - Interference in a glucose dehydrogenase-based glucose meter. PMID- 20360124 TI - B-type natriuretic peptides and the promise of improved cardiovascular risk prediction. PMID- 20360125 TI - Establishing a clinical basis for hsCRP in the prevention and treatment of cardiovascular disease. PMID- 20360126 TI - Validation of an enzyme immunoassay for detection and semiquantification of cannabinoids in oral fluid. AB - BACKGROUND: Oral fluid (OF) is gaining prominence as an alternative matrix for monitoring drugs of abuse in the workplace, criminal justice, and driving under the influence of drugs programs. It is important to characterize assay performance and limitations of screening techniques for Delta(9) tetrahydrocannabinol (THC) in OF. METHODS: We collected OF specimens by use of the Quantisal OF collection device from 13 daily cannabis users after controlled oral cannabinoid administration. All specimens were tested with the Immunalysis Sweat/OF THC Direct ELISA and confirmed by 2-dimensional GC-MS. RESULTS: The limit of detection was <1 microg/L THC equivalent, and the assay demonstrated linearity from 1 to 50 microg/L, with semiquantification to 200 microg/L. Intraplate imprecision (n = 7) ranged from 2.9% to 7.7% CV, and interplate imprecision (n = 20) was 3.0%-9.1%. Cross-reactivities at 4 microg/L were as follows: 11-hydroxy-THC, 198%; Delta(8)-tetrahydrocannabinol (Delta(8)-THC), 128%; 11-nor-9-carboxy-THC (THCCOOH), 121%; THC (target), 98%; cannabinol, 87%; THCCOOH-glucuronide, 11%; THC-glucuronide, 10%; and cannabidiol, 2.4%. Of 499 tested OF specimens, 52 confirmed positive (THC 2.0-290 microg/L), with 100% diagnostic sensitivity at the proposed Substance Abuse and Mental Health Services Administration screening cutoff of 4 microg/L cannabinoids and GC-MS cutoff of 2 microg/L THC. Forty-seven specimens screened positive but were not confirmed by 2D-GC-MS, yielding 89.5% diagnostic specificity and 90.6% diagnostic efficiency. Thirty-one of 47 unconfirmed immunoassay positive specimens were from 1 individual and contained >400 ng/L THCCOOH, potentially contributing to cross reactivity. CONCLUSIONS: The Immunalysis Sweat/OF THC Direct ELISA is an effective screening procedure for detecting cannabinoids in OF. PMID- 20360127 TI - An algorithm for acetylcholine receptor antibody testing in patients with suspected myasthenia gravis. PMID- 20360128 TI - Single-tube analysis of DNA methylation with silica superparamagnetic beads. AB - BACKGROUND: DNA promoter methylation is a signature for the silencing of tumor suppressor genes. Most widely used methods to detect DNA methylation involve 3 separate, independent processes: DNA extraction, bisulfite conversion, and methylation detection via a PCR method, such as methylation-specific PCR (MSP). This method includes many disconnected steps with associated losses of material, potentially reducing the analytical sensitivity required for analysis of challenging clinical samples. METHODS: Methylation on beads (MOB) is a new technique that integrates DNA extraction, bisulfite conversion, and PCR in a single tube via the use of silica superparamagnetic beads (SSBs) as a common DNA carrier for facilitating cell debris removal and buffer exchange throughout the entire process. In addition, PCR buffer is used to directly elute bisulfite treated DNA from SSBs for subsequent target amplifications. The diagnostic sensitivity of MOB was evaluated by methylation analysis of the CDKN2A [cyclin dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4); also known as p16(INK4a)] promoter in serum DNA of lung cancer patients and compared with that of conventional methods. RESULTS: Methylation analysis consisting of DNA extraction followed by bisulfite conversion and MSP was successfully carried out within 9 h in a single tube. The median pre-PCR DNA yield was 6.61-fold higher with the MOB technique than with conventional techniques. Furthermore, MOB increased the diagnostic sensitivity in our analysis of the CDKN2A promoter in patient serum by successfully detecting methylation in 74% of cancer patients, vs the 45% detection rate obtained with conventional techniques. CONCLUSIONS: The MOB technique successfully combined 3 processes into a single tube, thereby allowing ease in handling and an increased detection throughput. The increased pre-PCR yield in MOB allowed efficient, diagnostically sensitive methylation detection. PMID- 20360129 TI - Alternative splicing variant of kallikrein-related peptidase 8 as an independent predictor of unfavorable prognosis in lung cancer. AB - BACKGROUND: A relatively unexplored area for biomarker identification is alternative splice variants. We undertook this study to evaluate the usefulness of mRNA isoforms encoded by the KLK8 (kallikrein-related peptidase 8) gene as prognostic markers for lung cancer. METHODS: Real-time reverse-transcription PCR was used to analyze the mRNAs encoded by KLK8 (particularly 2 mRNA splice variants, KLK8-T3 and KLK8-T4) in 60 non-small-cell lung cancer (NSCLC) tumors and in paired unaffected tissues. The ratios of these mRNAs to those encoded by the KLK5, KLK6, KLK7, KLK10, KLK11, KLK13, and KLK14 genes were also determined and analyzed for correlations with various clinicopathologic variables. RESULTS: KLK8-T3 and KLK8-T4 were the most abundant of the 6 mRNA isoforms identified in lung tissues. The overall expression of the KLK8 gene and the amounts of the KLK8 T3 and KLK8-T4 mRNAs were significantly increased in lung tumor tissue (P < 0.0001). Univariate survival analysis revealed significant relationships of the relative concentrations of mRNA splice variants KLK8 (P = 0.043), KLK8-T3 (P = 0.037), and KLK8-T4 (P = 0.009) with overall survival (OS). Cox multivariate analysis indicated that the amount of KLK8-T4 mRNA was an independent prognostic factor for OS (relative risk = 3.90; P = 0.016) and that high KLK8-T4/KLK7, KLK8 T4/KLK10, and KLK8-T4/KLK11 mRNA ratios in NSCLC indicated increased risk of death. The increase was approximately 5-fold for the KLK8-T4/KLK7 and KLK8 T4/KLK10 ratios (P = 0.006, and P = 0.011, respectively) and 8-fold for the KLK8 T4/KLK11 ratio (P = 0.001). CONCLUSIONS: The KLK8-T4 alternative splice variant, alone or in combination, may be a new independent marker of unfavorable prognosis in lung cancer. PMID- 20360130 TI - Challenges in the diagnosis of the antiphospholipid syndrome. AB - BACKGROUND: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered. CONTENT: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and beta2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain. CONCLUSIONS: Despite updated APS criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their detection are needed to improve clinical risk assessment in APS. PMID- 20360131 TI - Mechanism and regulation of folate uptake by pancreatic acinar cells: effect of chronic alcohol consumption. AB - Folate plays an essential role in one-carbon metabolism, and a relationship exists between methyl group metabolism and pancreatic exocrine function. Little, however, is known about the mechanism(s) and regulation of folate uptake by pancreatic acinar cells and the effect of chronic alcohol use on the process. We addressed these issues using the rat-derived pancreatic acinar cell line AR42J and freshly isolated primary rat pancreatic acinar cells as models. We found [(3)H]folic acid uptake to be 1) temperature and pH dependent with a higher uptake at acidic than at neutral/alkaline pH; 2) saturable as a function of substrate concentration at both buffer pH 7.4 and 6.0; 3) inhibited by folate structural analogs and by anion transport inhibitors at both buffer pH 7.4 and 6.0; 4) trans-stimulated by unlabeled folate; 5) adaptively regulated by the prevailing extracellular folate level, and 6) inhibited by modulators of the cAMP/PKA-mediated pathway. Both the reduced folate carrier (RFC) and the proton coupled folate transporter (PCFT) were found to be expressed in AR42J and in primary pancreatic acinar cells, as well as in native human pancreas with expression of RFC being higher than PCFT. Chronic alcohol feeding of rats (4 wk; 36% of calories from ethanol) led to a significant decrease in folate uptake by freshly isolated primary pancreatic acinar cells compared with cells from pair fed controls; this effect was associated with a parallel decrease in the level of expression of RFC and PCFT. These studies reveal that folate uptake by pancreatic acinar cells is via a regulated carrier-mediated process which may involve RFC and PCFT. In addition, chronic alcohol feeding leads to a marked inhibition in folate uptake by pancreatic acinar cells, an effect that is associated with reduction in level of expression of RFC and PCFT. PMID- 20360132 TI - Genesis of multipeaked waves of the esophagus: repetitive contractions or motion artifact? AB - Multipeaked waves (MPW) in the distal esophagus occur frequently in patients with esophageal spastic motor disorders and diabetes mellitus and are thought to represent repetitive esophageal contractions. We aimed to investigate whether the relative motion between a stationary pressure sensor and contracted peristaltic esophageal segment that moves with respiration leads to the formation of MPW. We mathematically modeled the effect of relative movement between a moving pressure segment and a fixed pressure sensor on the pressure waveform morphology. We conducted retrospective analysis of 100 swallow-induced esophageal contractions in 10 patients, who demonstrated >30% MPW on high-resolution manometry (HRM) during standardized swallows. Finally, using HRM, we determined the effects of suspended breathing and hyperventilation on the waveform morphology in 10 patients prospectively. Modeling revealed that relative movement between a stationary pressure sensor and a moving contracted segment, contraction duration, contraction amplitude, respiratory frequency, and depth of respiration affects the waveform morphology. Retrospective analysis demonstrated a close temporal association with the onset of second and subsequent contractions in MPW with respiratory phase reversals. Numbers of peaks in MPW and respiratory phase reversals were closely related to the duration of contraction. In the prospective study, suspended breathing and hyperventilation resulted in a significant decrease and increase in the MPW frequency as well as the number of peaks within MPW respectively. We conclude that MPW observed during clinical motility studies are not indicative of repetitive esophageal contraction; rather they represent respiration-related movement of the contracted esophageal segment in relation to the stationary pressure sensor. PMID- 20360133 TI - Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland. AB - Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction. PMID- 20360134 TI - Peristalsis and fecal pellet propulsion do not require nicotinic, purinergic, 5 HT3, or NK3 receptors in isolated guinea pig distal colon. AB - The neuronal mechanism by which distension of the colon triggers peristalsis and the propulsion of colonic contents is incompletely understood. In this study, we used video imaging and spatiotemporal mapping techniques to investigate the neuroneuronal mechanisms underlying peristalsis in isolated guinea pig distal colon. In direct contrast to previous studies, we found that hexamethonium (100 muM-1 mM) or mecamylamine (20 muM) never abolished peristalsis or fecal pellet propulsion, although a temporary blockade of peristalsis was common, giving the impression perhaps that peristalsis was blocked permanently. During the initiation of peristalsis, the intraluminal propulsive force applied to an inserted fecal pellet was significantly reduced by hexamethonium 100 muM, even though, once initiated, the propagation velocity of fecal pellets was never reduced by nicotinic antagonists. In the presence of hexamethonium or mecamylamine, further addition of PPADS (10 muM), ondansetron (1 muM), and SR 142801 (300 nM) had no inhibitory effect on the propagation velocity of fecal pellets. In these preparations, antagonists for nicotinic, purinergic (P2), serotonergic (5-HT3), or tachykinergic (NK3) receptors always abolished responses to the agonists for these receptors, confirming that when peristalsis occurred, nicotinic, P2, 5-HT3, and NK3 receptors were blocked. Tetrodotoxin abolished nonnicotinic peristalsis. In summary, nicotinic transmission contributes to excitatory neuroneuronal transmission underlying peristalsis and fecal pellet propulsion but is not required for peristalsis, nor fecal pellet propulsion, as once thought. These observations could be explained by an excitatory nonnicotinic neuroneuronal pathway that can generate peristalsis and induce normal fecal pellet propagation velocities but does not require nicotinic, P2, 5-HT3, or NK3 receptors. PMID- 20360135 TI - IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis. AB - Interleukin-(IL)-4 and IL-13 signal through heterodimeric receptors containing a common IL-4 receptor-alpha (IL-4Ralpha) subunit, which is important for protection against helminth infections, including schistosomiasis. Previous studies demonstrated important roles for IL-4Ralpha-responsive hematopoietic cells, including T cells and macrophages in schistosomiasis. In this study, we examined the role of IL-4Ralpha responsiveness by nonhematopoietic smooth muscle cells during experimental acute murine schistosomiasis. Comparative Schistosoma mansoni infection studies with smooth muscle cell-specific IL-4Ralpha-deficient (SM-MHC(cre)IL-4Ralpha(-/flox)) mice, heterozygous control (IL-4Ralpha(-/flox)) mice, and global IL-4Ralpha-deficient (IL-4Ralpha(-/-)) mice were conducted. S. mansoni-infected SM-MHC(cre)IL-4Ralpha(-/flox) mice showed increased weight loss and earlier mortalities compared with IL-4Ralpha(-/flox) mice, despite comparable T(H)2/type 2 immune responses. In contrast to highly susceptible IL-4Ralpha deficient mice, increased susceptibility in SM-MHC(cre)IL-4Ralpha(-/flox) mice was not accompanied by intestinal tissue damage and subsequent sepsis. However, both susceptible mutant mouse strains failed to efficiently expel eggs, demonstrated by egg reduction in the feces compared with control mice. Reduced egg expulsion was accompanied by impaired IL-4/IL-13-mediated hypercontractile intestinal responses, which was present in the more resistant control mice. Together, we conclude that IL-4Ralpha responsiveness by smooth muscle cells and subsequent IL-4- and IL-13-mediated hypercontractility are required for host protection during acute schistosomiasis to efficiently expel S. mansoni eggs and to prevent premature mortality. PMID- 20360137 TI - The future of aptamers in medicine. AB - Aptamers, simply described as chemical antibodies, are synthetic oligonucleotide ligands or peptides that can be isolated in vitro against diverse targets including toxins, bacterial and viral proteins, virus-infected cells, cancer cells and whole pathogenic microorganisms. Aptamers assume a defined three dimensional structure and generally bind functional sites on their respective targets. They possess the molecular recognition properties of monoclonal antibodies in terms of their high affinity and specificity. The applications of aptamers range from diagnostics and biosensing, target validation, targeted drug delivery, therapeutics, templates for rational drug design to biochemical screening of small molecule leads compounds. This review describes recent progress made in the application of biomedically relevant aptamers and relates them to their future clinical prospects. PMID- 20360136 TI - Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. AB - BACKGROUND: Tumour necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons. OBJECTIVE: To determine whether infliximab might be discontinued after achievement of LDA in patients with RA and to evaluate progression of articular destruction during the discontinuation. METHODS: 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score, including a 28-joint count (DAS28) was <3.2 (LDA) for 24 weeks, were studied. RESULTS: The mean disease duration of the 114 patients was 5.9 years, mean DAS28 5.5 and mean modified total Sharp score (mTSS) 63.3. After maintaining LDA for >24 weeks by infliximab treatment, the drug was discontinued and DAS28 in 102 patients was evaluated at year 1. Fifty-six patients (55%) continued to have DAS28<3.2 and 43% reached DAS<2.6 at 1 year after discontinuing infliximab. For 46 patients remission induction by Remicade in RA (RRR) failed: disease in 29 patients flared within 1 year and DAS28 was >3.2 at year 1 in 17 patients. Yearly progression of mTSS (DeltaTSS) remained <0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated DeltamTSS was 0.3 and 1.6 and Health Assessment Questionnaire-Disability Index was 0.174 and 0.614 in the RRR-achieved and RRR-failed groups, respectively, 1 year after the discontinuation. CONCLUSION: After attaining LDA by infliximab, 56 (55%) of the 102 patients with RA were able to discontinue infliximab for >1 year without progression of radiological articular destruction. PMID- 20360139 TI - Design of a multiplex PCR assay for the simultaneous detection and confirmation of Neisseria gonorrhoeae. AB - OBJECTIVES: To improve the detection of Neisseria gonorrhoeae by designing a multiplex PCR assay using two N gonorrhoeae-specific genes as targets, thereby providing detection and confirmation of a positive result simultaneously. METHODS: PCR primers were designed to detect two N gonorrhoeae genes, namely porA and pgi1. Primers for an internal control targeting the ompW gene of Vibrio cholerae were also designed and incorporated in the assay. The DNA of 45 clinical isolates including 33 N gonorrhoeae isolates, seven non-gonococcal Neisseria species, and five non-Neisseria species was tested using the multiplex PCR assay. RESULTS: All 33 N gonorrhoeae isolates were successfully detected by the assay and none of the non-gonococcal isolates was detected. The assay showed a sensitivity and specificity of 100%, and a limit of detection of 1.25 ng of DNA. CONCLUSION: This multiplex PCR assay offers a sensitive and specific assay suitable for the detection of N gonorrhoeae, and offers real potential for diagnostic use. PMID- 20360140 TI - Toxoplasma tachyzoites from cell culture are more appropriate in some situations. AB - BACKGROUND: Laboratories traditionally culture toxoplasma tachyzoites in animals for testing and experimental use. This article considers why available cell culture methods are not used more often. AIM: To compare HeLa cell culture and animal culture for production of toxoplasma tachyzoites. METHODS: In 2000 HeLa culture replaced animal culture for continuous production of toxoplasma tachyzoites in the Scottish Toxoplasma Reference Laboratory. The performance of animal culture (1994-1998) was compared with HeLa culture (2004-2008). A PubMed search was carried out for 1998 and 2008 to assess the culture methods used in laboratories. RESULTS: Animal culture was able to produce higher yields of tachyzoites (10(9) from a cotton rat peritoneal harvest compared to 10(7) from a 75 cm(2) cell culture flask) but significantly more HeLa cultures were successful (93% versus 84%; p=0.025). There was no difference in the quality of tachyzoites from animal and HeLa cultures as demonstrated by the high levels of success in the dye test. HeLa culture offered significant advantages in flexibility and control. A review of the literature showed no significant change in the method of culture used in laboratories between 1998 and 2008 (p=0.36). CONCLUSION: The availability of cell culture methods and the increasingly stringent regulations on the use of animals have not resulted in a decline in the use of animal culture. Animals are necessary for certain experiments but many studies could use cell-culture-derived parasites. PMID- 20360141 TI - Proximal type epithelioid sarcoma arising in the base of the skull: a diagnostic challenge. PMID- 20360142 TI - Isolated eosinophilic coronary arteritis. PMID- 20360143 TI - Simple hand-held metal detectors are an effective means of detecting cardiac pacemakers in the deceased prior to cremation. AB - The hazard of undetected cardiac pacemakers exploding in crematoria is well described. This short report describes the use of an affordable hand-held metal detector to detect cardiac pacemakers. Over the course of a year, the metal detector located 100% of cardiac pacemakers in a district general hospital mortuary. A simple model using pigskin and fat is also used to demonstrate the effectiveness in vitro. Commercially purchased hand-held metal detectors should be used in all mortuaries responsible for detection and removal of cardiac pacemakers prior to cremation. PMID- 20360144 TI - Immunohistochemistry and molecular analyses in myeloid sarcoma of the breast in a patient with relapse of NPM1-mutated and FLT3-mutated AML after allogeneic stem cell transplantation. AB - Myeloid sarcoma of the breast is a rare manifestation of acute myeloid leukaemia (AML). This report describes a patient who was diagnosed with AML FAB M2. Molecular analysis showed evidence of an NPM1 mutation (subtype A) and internal tandem duplications of the FLT3 gene (FLT3-ITD). Eight months after allogeneic stem cell transplantation, the patient developed a palpable mass in the left breast initially suspected as breast carcinoma. Core needle biopsy of the lesion resulted in diagnosis of myeloid sarcoma. Molecular analysis of formalin-fixed specimens of the breast tumour confirmed the known FLT3 and NPM1 gene mutations. Immunohistochemically, an aberrant cytoplasmic staining pattern for NPM1 and overexpression of FLT3 were demonstrated. The myeloid sarcoma showed complete transient resolution following treatment with the kinase inhibitor sorafenib. However, the patient developed bone marrow relapse and died in fatal cerebral haemorrhage 1 year after initial diagnosis of AML. In summary, combined molecular and immunohistochemical examination of NPM1 and FLT3 is helpful in the diagnosis of extramedullary manifestations of AML in core needle biopsies. PMID- 20360145 TI - Negotiating care: patient tactics at an urban South African hospital. AB - OBJECTIVES: To examine the various ways in which patients sought to influence the care they received in the admission and adult medical services of a large urban, academic hospital in South Africa. These included the steps taken by patients to increase their access to services and improve their experience of care. METHODS: Part of a qualitative study of rationing behaviour, the methods combined, observations, interviews and a survey. RESULTS: Patient's actions were oriented to two main goals: obtaining care and preserving their sense of self and dignity. These actions shaped patients' pathways in five key ways: meeting the entry criteria for admission; presenting as a cooperative, expert patient; mobilizing social networks among health care staff; making use of complaints mechanisms; and deploying narratives of resistance. CONCLUSION: Patients made tactical use of small spaces at the margins of the health care system. Although, with some exceptions, they had limited impact on the care received in the hospital, they highlight patients as active players and point to the ways in which patient agency can be strengthened in the light of the shift towards chronic disease care and greater patient involvement in care. PMID- 20360146 TI - Validation of a rat seminiferous tubule culture model as a suitable system for studying toxicant impact on meiosis effect of hexavalent chromium. AB - There is evidence that exposure to environmental factors is at least partly responsible for changes in semen quality observed over the past decades. The detection of reproductive toxicants under Registration, Evaluation and Authorisation of Chemicals (REACH) will impact animal use for regulatory safety testing. We first validated a model of culture of rat seminiferous tubules for toxicological studies on spermatogenesis. Then, using this model of culture, we assessed the deleterious effects of 1, 10, and 100 microg/l hexavalent chromium [Cr(VI)] on meiotic cells. The prophase I of meiosis was studied in vivo and ex vivo. Bromo-2'-deoxyuridine (BrdU) was used to describe the kinetics of germ cell differentiation. SCP3 labeling allowed to establish the distribution of the stages of the meiotic prophase I and to perform a qualitative study of the pachytene stage in the absence or presence of Cr(VI). The development of the meiotic step of pubertal rats was similar in vivo and ex vivo. The number of total cells appeared not affected by the presence of Cr(VI) irrespective of its concentration. However, the numbers of late spermatocytes and of round spermatids were decreased by Cr(VI) even at the lower concentration. The percentage of synaptonemal complex abnormalities increased slightly with the time of culture and dramatically with Cr(VI) concentrations. This model of culture appears suitable for toxicological studies. This study shows that Cr(VI) is toxic for meiotic cells even at low concentrations, and its toxicity increases in a dose dependent manner. PMID- 20360147 TI - Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk. AB - Matrix metalloproteinase (MMP) 2, MMP7 and MMP9 are important members of the MMP family. Four polymorphisms in the promoter region of these MMPs, which are MMP2 1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G and MMP9 -1562 C>T, have been reported to be functional and may contribute to genetic susceptibility to cancers. However, the associations between these polymorphisms and cancer risk remain inconclusive due to conflicting results from different case-control studies. To better evaluate the role of these polymorphisms in cancer development, we conducted a meta-analysis that included 51 studies, with more than 40,000 subjects. The results showed that under dominant genetic model, MMP2 -1306 T was associated with lower susceptibility to lung cancer [odds ratio (OR) = 0.50, 95% confidence interval (CI) 0.43-0.59, P(heterogeneity) = 0.147, I(2) = 44.1%], head and neck cancer (OR = 0.53, 95% CI 0.41-0.69, P(heterogeneity) = 0.974, I(2) = 0.0%) and oesophageal cancer (OR = 0.67, 95% CI 0.55-0.80, P(heterogeneity) = 0.593, I(2) = 0.0%); MMP2-735T was associated with lower risk in lung cancer (OR = 0.65, 95%CI 0.53-0.79, P(heterogeneity) = 0.42, I(2) = 0.0%) and oesophageal cancer (OR = 0.84, 95% CI 0.70-0.99, P(heterogeneity) = 0.206, I(2) = 37.4%); MMP7 -181 AG and GG genotype carriers had an increased gastric cancer risk (OR = 1.90, 95% CI 1.43 2.51, P(heterogeneity) = 0.992, I(2) = 0.0%) and MMP9 -1562 C>T was not associated with cancer risk in the whole group analysis (OR = 0.99, 95% CI 0.91 1.08, P(heterogeneity) = 0.419, I(2) = 3.0%) and subgroup analyses. In all, our meta-analysis suggests that MMP2 -1306 C>T, MMP2 -735 C>T and MMP7 -181 A>G may play allele-specific roles in cancer development, while MMP9 -1562 C>T may not be a major risk factor for most cancer types. Large case-control studies should be performed to clarify the possible roles of these four polymorphisms in different kinds of cancer in more detail. PMID- 20360148 TI - School demands and subjective health complaints among Swedish schoolchildren: a multilevel study. AB - OBJECTIVES: As children spend a great deal of their time in school, the climate in the classroom can constitute a resource, but also a risk factor in the development of the pupils' health. The aim of the present study was to determine the extent to which demands in the classroom are associated with subjective health complaints in Swedish schoolchildren. METHODS: Data from the 2001/2002 and 2005/2006 Swedish cross-national Health Behaviour in School-aged Children (HBSC) survey were analysed using a multilevel logistic regression technique. RESULTS: The study demonstrated a substantial variation between school classes in pupils' subjective health complaints. In school classes with high demands, the odds of having subjective health complaints was about 50% higher than in school classes with low demands. Further, the results indicated that these effects were mediated by sex so as to girls being more affected by high levels of demands in the school class. CONCLUSIONS: The findings are important since they point at the crucial role that teachers play in creating a favourable school climate. Therefore interventions aiming at supporting teachers to set realistic demands and expectations are one way to improve the school climate. Such interventions should also make clear the need to take into consideration the fact that the school class effect was mediated by sex, i.e. girls being more vulnerable to high level of school class demands. PMID- 20360150 TI - Rehabilitation in practice: Spasticity management. AB - This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'The trainee consistently demonstrates a knowledge of the pathophysiology of various specific impairments including spasticity'. Spasticity is an extremely common feature of chronic neurological conditions and, if badly managed, it can result in pain, contractures and pressure sores, all of which can impact on function. It is therefore essential that a multidisciplinary management strategy is in place to help the individual manage their particular situation through education with timely access to interventions including instigation of a physical management programme and medication such as baclofen, tizanidine, dantrolene, benzodiazepines and gabapentin. Further treatment options for focal spasticity are botulinum toxin and phenol nerve blocks or intrathecal baclofen or phenol for predominant lower limb spasticity. Ongoing assessment with the use of appropriate outcome measures can both guide choice of treatment and monitor efficacy. PMID- 20360151 TI - A randomized controlled trial of a wellness intervention for women with fibromyalgia syndrome. AB - OBJECTIVE: To examine the effects of a wellness intervention, Lifestyle Counts, for women with fibromyalgia syndrome on the level of self-efficacy for health promoting behaviours, health-promoting activity and perceived quality of life. DESIGN: A randomized controlled single-blinded trial with treatment and attention control groups. SETTING: Community in the southwestern United States. SUBJECTS: Convenience sample of 187 women (98 treatment, 89 attention control) with fibromyalgia syndrome (mean age = 53.08 years, SD 9.86). INTERVENTION: The two phase Lifestyle Counts intervention programme included lifestyle change classes for eight weeks, with goal-setting and telephone follow-up for three months. Participants in the attention-control group were offered an equivalent amount of contact in classes on general disease-related information and health education topics and unstructured follow-up phone calls. Participants were followed for a total of eight months after baseline. OUTCOME MEASURES: Self-report instruments measuring self-efficacy for health behaviours, health-promotion behaviours and health-related quality of life (SF-36 and the Fibromyalgia Impact Questionnaire) were completed at baseline, two months (after the classes), five months (after telephone follow-up) and at eight months. RESULTS: Both groups improved significantly (P<0.05) over time on the measures of self-efficacy, health behaviours, fibromyalgia impact and quality of life. There were significant group x time interactions for scores on the Health Promoting Lifestyle II subscales of physical activity and stress management. CONCLUSIONS: The Lifestyle Counts wellness intervention holds promise for improving health-promoting behaviours and quality of life of women with fibromyalgia syndrome. PMID- 20360152 TI - Comparison of the effects of a physiotherapist-supervised exercise programme and a self-supervised exercise programme on quality of life in patients with Parkinson's disease. AB - OBJECTIVES: To compare the effects of a physiotherapist-supervised exercise programme in an exercise unit and self-supervised home exercise programme on quality of life in patients with Parkinson's disease. DESIGN: Assessor-blinded, quasi-randomized trial (alternate allocation). SETTING: An outpatient exercise unit; home settings. PARTICIPANTS: Thirty patients with idiopathic Parkinson's disease, Hoehn & Yahr I-III, stable medication use. INTERVENTIONS: Patients were included in the physiotherapist-supervised or home group. The exercise programme was performed for 10 weeks, three times/week either under the supervision of a physiotherapist or at home without supervision. MAIN OUTCOME MEASURES: Parkinson's Disease Quality of Life Questionnaire (PDQLQ), Nottingham Health Profile (NHP), Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI). RESULTS: Patients in the supervised physiotherapy group improved more than the home exercise group in Parkinson's Disease Quality of Life Questionnaire (total score, Parkinson's symptoms, emotional function), Nottingham Health Profile total, Unified Parkinson's Disease Rating Scale (all domains) and Beck Depression Inventory scores. CONCLUSIONS: The exercise programme under physiotherapist supervision was found to be more effective at improving activities of daily living, motor, mental, emotional functions and general health quality in patients with Parkinson's disease compared with a self-supervised home programme. PMID- 20360153 TI - Is achievement of short-term goals a valid measure of patient progress in inpatient neurological rehabilitation? AB - OBJECTIVE: To determine whether the use of short-term goal setting is effective in monitoring patient progress, with regard to achievement of rehabilitation goals for discharge and predicted length of hospital stay. DESIGN: A prospective observational cohort study. SETTING: An inpatient rehabilitation unit co-located with a large tertiary teaching hospital. SUBJECTS: Consecutive cases admitted to rehabilitation with a neurological condition and a planned length of stay of three weeks or longer. PROCEDURE: Discharge and short-term goals and predicted length were set in the initial team meeting. Goals were set, and achievement scored, in the domains of health, social functioning, communication and cognition, mobility and activities of daily living (ADLs) and a composite goal of global function. Actual length of stay and discharge destination were recorded. RESULTS: Data from 53 consecutive cases were examined, with 45 cases returning home. The median length of stay was 49 days (interquartile (IQ) 30-74). Significant correlations (P<0.05) were demonstrated between short-term goal achievement and discharge goals for continence (rho = 0.62), transfers (rho = 0.53), personal activities of daily living (rho = 0.47) and global function (rho = 0.62). For those that returned home, there were significant correlations (P<0.05) between adherence to predicted length of stay and achieving their initial goals in transfers (rho = 0.44), walking (rho = 0.51) and global function (rho = 0.55). CONCLUSION: Short-term goal setting is a valid measure of patient progress in inpatient neurological rehabilitation and can be used to identify patients who are not progressing as anticipated, facilitating review of the rehabilitation plan. PMID- 20360154 TI - Editorial on generic or global outcome measures in rehabilitation. PMID- 20360156 TI - Anterior internal capsule volumes increase in patients with schizophrenia switched from typical antipsychotics to olanzapine. AB - Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-treated patients than controls (p = 0.009). Patients treated with greater amounts of chlorpromazine-equivalent daily dosage had smaller anterior internal capsule volumes at baseline (r = -0.65, p = 0.04). At follow up, after being switched to olanzapine, there were no significant differences between patients and controls. Patients with schizophrenia had a significant 25% increase in anterior internal capsule volume from baseline to follow-up compared with controls (p = 0.04). These effects were most prominent in the anterior limb of the internal capsule, which consists of fronto-thalamic pathways, and were not statistically significant in the posterior limb of the internal capsule or corpus callosum. Olanzapine may be effective in normalizing fronto-thalamic structural connectivity in schizophrenia. PMID- 20360157 TI - Hospital psychiatric comorbidity and its role in heroin dependence treatment outcomes using naltrexone implant or methadone maintenance. AB - Our objectives were to (i) estimate lifetime prevalence of psychiatric comorbidity in heroin users and (ii) evaluate psychiatric comorbidity as a predictor of drug-related hospitalization following either (a) methadone maintenance or (b) naltrexone implant treatment. Our method consisted of retrospective, longitudinal follow-up using prospectively collected, state-wide hospital data on two cohorts of heroin-dependent persons (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), first time treated with naltrexone implant (n = 317) or methadone (n = 521) between January 2001 and December 2002. Outcome measures were: (i) prevalence of comorbidity and (ii) changes in risk for drug-related hospitalization - categorized as 'opioid drugs', 'non-opioid drugs', and 'any drug' - to 3.5 years post-treatment. Nearly 32% had psychiatric comorbidity. In both cohorts, comorbid patients generally had significantly greater odds of drug-related hospitalization pre-treatment compared with non-comorbid counterparts. These differences generally reduced in magnitude post-treatment. Comorbid naltrexone-treated patients had less 'opioid' and 'any drug' related hospitalizations post-treatment. Similarly, comorbid methadone treated patients had reduced hospitalization risk for 'non-opioid' and 'any drug' related hospitalization post-treatment. Treatment of persons without depression, anxiety, or personality disorder with naltrexone implant was associated with increased risk of 'non-opioid' drug-related hospitalization, while methadone treatment was associated with increased risk of 'opioid' drug-related hospitalization. Although comorbid heroin users entered treatment with significantly higher risk of drug-related hospitalization than non-comorbid users, substantial reductions in drug-related hospitalization were generally observed post-treatment. This challenges the view that comorbidity predicts poor drug treatment outcomes. Differences in research methodology were noted; recommendation for rigorous analytical methodology in future research on assessing treatment outcomes was accordingly offered. PMID- 20360158 TI - Emotion processing in schizophrenia: fMRI study of patients treated with risperidone long-acting injections or conventional depot medication. AB - We employed two event-related functional magnetic resonance imaging tasks using the pictures of mild and intense facial emotions of fear or happiness. The sample comprised 16 chronic schizophrenia patients treated with risperidone long-acting injections (RLAI), 16 patients treated with conventional antipsychotic depots (CONV) and 16 healthy controls (HC). The HC and RLAI groups demonstrated greater activation in the left amygdala in response to intensively fearful faces, and in right cerebellum to intensively happy faces compared with CONV patients. The CONV group demonstrated under-activation in the right temporal pole in response to intensively happy faces (compared with HC) and over-activation in ventro-medial prefrontal cortex (VMPFC) in response to both intensively happy and fearful expressions, compared with HC and RLAI groups. Our results suggest that networks implicated in the allocation of attentional resources (VMPFC) and emotion processing (amygdala, cerebellum) are differentially affected in patients on CONV versus RLAI. PMID- 20360159 TI - Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test. AB - Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Accordingly, nicotine enhances antidepressant-like actions of reuptake inhibitors selective for serotonin or noradrenaline in the mouse forced swim test and the mouse tail suspension test. Both high-affinity alpha4beta2 and low-affinity alpha7 nicotinic acetylcholine receptor subtypes are implicated in nicotine-mediated release of serotonin and noradrenaline. The present study therefore investigated whether selective agonism of alpha4beta2 or alpha7 nicotinic acetylcholine receptors would affect the mouse forced swim test activity of two antidepressants with distinct mechanisms of action, namely the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine. Subthreshold and threshold doses of citalopram (3 and 10 mg/kg) or reboxetine (10 and 20 mg/kg) were tested alone and in combination with the novel alpha4beta2-selective partial nicotinic acetylcholine receptor agonist, NS3956 (0.3 and 1.0 mg/kg) or the alpha7 selective nicotinic acetylcholine receptor agonist, PNU-282987 (10 and 30 mg/kg). Alone, NS3956 and PNU-282987 were devoid of activity in the mouse forced swim test, but both 1.0 mg/kg NS3956 and 30 mg/kg PNU-282987 enhanced the effect of citalopram and also reboxetine. The data suggest that the activity of citalopram and reboxetine in the mouse forced swim test can be enhanced by agonists at either alpha4beta2 or alpha7 nicotinic acetylcholine receptors, suggesting that both nicotinic acetylcholine receptor subtypes may be involved in the nicotine enhanced action of antidepressants. PMID- 20360160 TI - Meta-analyses and antidepressant prescribing. PMID- 20360161 TI - Auditory nerve compression: a forgotten treatable cause for tinnitus. PMID- 20360162 TI - Impact of secondary prevention on survival in patients with stroke: from clinical trials to clinical practice. PMID- 20360163 TI - Active upper-limb movement can be improved in hemiplegic patients by botulinum toxin injection. PMID- 20360164 TI - Neurological picture. Secondary parkinsonism due to arachnoid cyst of the frontal lobe. PMID- 20360165 TI - Magnetic resonance spectroscopy evaluation in patients with neuromyelitis optica. AB - OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory disease associated with optic neuritis and myelitis. Although some studies have reported multiple sclerosis (MS)-like lesions in 10-30% of NMO patients, brain MRI is usually normal. Several studies have observed metabolic abnormalities on MR spectroscopy in MS, even in normal-appearing white matter (NAWM). To the authors' knowledge, MR spectroscopy has never been used to investigate NMO. The aim of this study was to evaluate metabolic abnormalities in the NAWM and normal-appearing grey matter (NAGM) of NMO patients. METHODS: The authors evaluated 24 patients (17 women and seven men, with a mean age of 44.6 years). NMO was diagnosed according to revised criteria. All patients had a brain and spinal cord MR imaging including MR spectroscopy sequences in both NAWM and NAGM. Patients were compared with 12 healthy subjects. RESULTS: NAA/creatinine ratios in NAWM (1.89 + or - 0.26 in NMO compared with 1.91 + or - 0.15 in control subjects) and NAGM (1.62 + or - 0.21 compared with 1.59 + or - 0.18) were normal, as were choline/creatinine ratios in NAWM (1.03 + or - 0.18 compared with 1.08 + or - 0.14) and NAGM (0.89 + or - 0.2 compared with 0.94 + or - 0.2). Myo-inositol values in NAWM were also normal (0.42 + or - 0.12 compared with 0.42 + or - 0.18). CONCLUSION: Our results are clearly different from those found in MS, where NAA is frequently decreased and choline increased, even in NAWM. Our findings could have an impact on the differentiation between MS and NMO. PMID- 20360166 TI - Survival in progressive supranuclear palsy and frontotemporal dementia. AB - OBJECTIVE: To compare survival and to identify prognostic predictors for progressive supranuclear palsy and frontotemporal dementia. BACKGROUND: Progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) are related disorders. Homozygosity for H1 haplotype is associated with PSP, whereas several MAPT mutations have been identified in FTLD-tau. Survival duration probably reflects underlying pathophysiology or disease. METHODS: Patients with PSP and FTD were recruited by nationwide referral. Survival of 354 FTD patients was compared with that of 197 PSP patients. Cox regression analysis was performed to identify prognostic predictors. FTLD-tau was defined as Pick disease and FTDP 17 with MAPT mutations. Semiquantitative evaluation of tau-positive pathology was performed on all pathologically proven cases. RESULTS: The median survival of PSP patients (8.0 years; 95% CI 7.3 to 8.7) was significantly shorter than that of FTD patients (9.9 years; 95% CI 9.2 to 10.6). Corrected for demographic differences, PSP patients were still significantly more at risk of dying than FTD patients. In PSP, male gender, older onset-age and higher PSP Rating Scale score were identified as independent predictors for shorter survival, whereas in FTD a positive family history and an older onset-age were associated with a poor prognosis. The difference in hazard rate was even more pronounced when comparing pathologically proven cases of PSP with FTLD-tau. CONCLUSION: Survival of PSP patients is shorter than that of FTD patients, and probably reflects a more aggressive disease process in PSP. Independent predictors of shorter survival in PSP were male gender, older onset-age and higher PSP rating scale score, whereas in FTD a positive family history and higher onset-age were predictors for worse prognosis. PMID- 20360167 TI - Neurological picture. Ascending paralysis from malignant leptomeningeal melanomatosis. PMID- 20360168 TI - Carbamazepine responsive typewriter tinnitus from basilar invagination. AB - Basilar invagination due to a congenital skeletal disorder kinked the brainstem at the ponto-medullary junction causing both auditory nerves to make an acute turn at the porus acousticus. The associated bilateral asynchronous clicking tinnitus responded to carbamazepine. PMID- 20360169 TI - Can we see personal identity loss? A functional imaging study of typical 'hysterical amnesia'. PMID- 20360170 TI - A case of haemophagocytic syndrome presenting with oculogyric crises. PMID- 20360171 TI - A MELAS/MERRF phenotype associated with the mitochondrial DNA 5521G>A mutation. PMID- 20360172 TI - Taxing soft drinks and restricting access to vending machines to curb child obesity. AB - One of the largest drivers of the current obesity epidemic is thought to be excessive consumption of sugar-sweetened beverages. Some have proposed vending machine restrictions and taxing soft drinks to curb children's consumption of soft drinks; to a large extent, these policies have not been evaluated empirically. We examine these policies using two nationally representative data sets and find no evidence that, as currently practiced, either is effective at reducing children's weight. We conclude by outlining changes that may increase their effectiveness, such as implementing comprehensive restrictions on access to soft drinks in schools and imposing higher tax rates than are currently in place in many jurisdictions. PMID- 20360173 TI - Soda taxes, soft drink consumption, and children's body mass index. AB - Taxes on sugar-sweetened beverages have been proposed to combat obesity. Using data on state sales taxes for soda and individual-level data on children, we examine whether small taxes are likely to change consumption and weight gain or whether larger tax increases would be needed. We find that existing taxes on soda, which are typically not much higher than 4 percent in grocery stores, do not substantially affect overall levels of soda consumption or obesity rates. We do find, however, that subgroups of at-risk children--children who are already overweight, come from low-income families, or are African American--may be more sensitive than others to soda taxes, especially when soda is available at school. A greater impact of these small taxes could come from the dedication of the revenues they generate to other obesity prevention efforts rather than through their direct effect on consumption. PMID- 20360174 TI - Comparison of work-related ill health reporting by occupational physicians and general practitioners. AB - BACKGROUND: The provision of occupational health (OH) services to the UK population is limited and concentrated in certain industries. Occupational physicians (OPs) therefore see a different subset of the population than general practitioners (GPs) and their recognition of work-related ill health may differ. AIMS: To examine how reports submitted by OPs and GPs compare and to discuss how biases may affect diagnostic and demographic differences. METHODS: The Health & Occupation Reporting network collects information on work-related ill health. OPs and GPs report case details, including demographic information, occupation, industry and suspected agent/task/event. Differences in reporting patterns were assessed. RESULTS: Musculoskeletal and mental ill-health reports made up over 80% of reports to both schemes although the likelihood ratio (LR) showed OPs were 78% more likely to report a psychological case than GPs. OPs were also more (18%) likely to report a female case. Health & social care was the industry most frequently reported by both groups; however, this was in greatly differing proportions (OPs 38%, GPs 14%). When LRs were adjusted for industry, this reduced the likelihood of an OP reporting cases of mental ill health (to 40%) and found them 10% less likely to report females than GPs. CONCLUSIONS: OP and GP reporting patterns highlight the variation in OH provision and its influence on the data provided. OPs are best placed to report on health and work relationships; however, as some sectors have poor access to OH services, reports from suitably trained GPs will help inform about this 'blind spot'. PMID- 20360175 TI - Characterization of tRNA(Cys) processing in a conditional Bacillus subtilis CCase mutant reveals the participation of RNase R in its quality control. AB - We generated a conditional CCase mutant of Bacillus subtilis to explore the participation in vivo of the tRNA nucleotidyltransferase (CCA transferase or CCase) in the maturation of the single-copy tRNA(Cys), which lacks an encoded CCA 3' end. We observed that shorter tRNA(Cys) species, presumably lacking CCA, only accumulated when the inducible Pspac : cca was introduced into an rnr mutant strain, but not in combination with pnp. We sequenced the tRNA 3' ends produced in the various mutant tRNA(Cys) species to detect maturation and decay intermediates and observed that decay of the tRNA(Cys) occurs through the addition of poly(A) or heteropolymeric tails. A few clones corresponding to full size tRNAs contained either CCA or other C and/or A sequences, suggesting that these are substrates for repair and/or decay. We also observed editing of tRNA(Cys) at position 21, which seems to occur preferentially in mature tRNAs. Altogether, our results provide in vivo evidence for the participation of the B. subtilis cca gene product in the maturation of tRNAs lacking CCA. We also suggest that RNase R exoRNase in B. subtilis participates in the quality control of tRNA. PMID- 20360176 TI - Genetic diversity in Campylobacter jejuni is associated with differential colonization of broiler chickens and C57BL/6J IL10-deficient mice. AB - Previous studies have demonstrated that Campylobacter jejuni, the leading causative agent of bacterial food-borne disease in the USA, exhibits high frequency genetic variation that is associated with changes in cell-surface antigens and ability to colonize chickens. To expand our understanding of the role of genetic diversity in the disease process, we analysed the ability of three C. jejuni human disease isolates (strains 11168, 33292 and 81-176) and genetically marked derivatives to colonize Ross 308 broilers and C57BL/6J IL10 deficient mice. C. jejuni colonized broilers at much higher efficiency (all three strains, 23 of 24 broilers) than mice (11168 only, 8 of 24 mice). C. jejuni 11168 genetically marked strains colonized mice at very low efficiency (2 of 42 mice); however, C. jejuni reisolated from mice colonized both mice and broilers at high efficiency, suggesting that this pathogen can adapt genetically in the mouse. We compared the genome composition in the three wild-type C. jejuni strains and derivatives by microarray DNA/DNA hybridization analysis; the data demonstrated a high degree of genetic diversity in three gene clusters associated with synthesis and modification of the cell-surface structures capsule, flagella and lipo oligosaccharide. Finally, we analysed the frequency of mutation in homopolymeric tracts associated with the contingency genes wlaN (GC tract) and flgR (AT tracts) in culture and after passage through broilers and mice. C. jejuni adapted genetically in culture at high frequency and the degree of genetic diversity was increased by passage through broilers but was nearly eliminated in the gastrointestinal tract of mice. The data suggest that the broiler gastrointestinal tract provides an environment which promotes outgrowth and genetic variation in C. jejuni; the enhancement of genetic diversity at this location may contribute to its importance as a human disease reservoir. PMID- 20360177 TI - Genetic diversity in Italian Lactobacillus sanfranciscensis strains assessed by multilocus sequence typing and pulsed-field gel electrophoresis analyses. AB - Lactobacillus sanfranciscensis is a lactic acid bacterium that characterizes the sourdough environment. The genetic differences of 24 strains isolated in different years from sourdoughs, mostly collected in Italy, were examined and compared by PFGE and multilocus sequence typing (MLST). The MLST scheme, based on the analysis of six housekeeping genes (gdh, gyrA, mapA, nox, pgmA and pta) was developed for this study. PFGE with the restriction enzyme ApaI proved to have higher discriminatory power, since it revealed 22 different pulsotypes, while 19 sequence types were recognized through MLST analysis. Notably, restriction profiles generated from three isolates collected from the same firm but in three consecutive years clustered in a single pulsotype and showed the same sequence type, emphasizing the fact that the main factors affecting the dominance of a strain are correlated with processing conditions and the manufacturing environment rather than the geographical area. All results indicated a limited recombination among genes and the presence of a clonal population in L. sanfranciscensis. The MLST scheme proposed in this work can be considered a useful tool for characterization of isolates and for in-depth examination of the strain diversity and evolution of this species. PMID- 20360178 TI - Extracellular enzymes affect biofilm formation of mucoid Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa secretes a variety of hydrolases, many of which contribute to virulence or are thought to play a role in the nutrition of the bacterium. As most studies concerning extracellular enzymes have been performed on planktonic cultures of non-mucoid P. aeruginosa strains, knowledge of the potential role of these enzymes in biofilm formation in mucoid (alginate-producing) P. aeruginosa remains limited. Here we show that mucoid P. aeruginosa produces extracellular hydrolases during biofilm growth. Overexpression of the extracellular lipases LipA and LipC, the esterase EstA and the proteolytic elastase LasB from plasmids revealed that some of these hydrolases affected the composition and physicochemical properties of the extracellular polymeric substances (EPS). While no influence of LipA was observed, the overexpression of estA and lasB led to increased concentrations of extracellular rhamnolipids with enhanced levels of mono-rhamnolipids, elevated amounts of total carbohydrates and decreased alginate concentrations, resulting in increased EPS hydrophobicity and viscosity. Moreover, we observed an influence of the enzymes on cellular motility. Overexpression of estA resulted in a loss of twitching motility, although it enhanced the ability to swim and swarm. The lasB-overexpression strain showed an overall enhanced motility compared with the parent strain. Moreover, the EstA- and LasB-overproduction strains completely lost the ability to form 3D biofilms, whereas the overproduction of LipC increased cell aggregation and the heterogeneity of the biofilms formed. Overall, these findings indicate that directly or indirectly, the secreted enzymes EstA, LasB and LipC can influence the formation and architecture of mucoid P. aeruginosa biofilms as a result of changes in EPS composition and properties, as well as the motility of the cells. PMID- 20360179 TI - An RNA symbiont enhances heat tolerance and secondary homothallism in the oomycete Phytophthora infestans. AB - Some strains of Phytophthora infestans, the potato late blight pathogen, harbour a small extrachromosomal RNA called PiERE1. A previous study reported that this RNA symbiont does not noticeably affect its host. Here it is revealed that PiERE1 exerts subtle effects on P. infestans, which result in greater thermotolerance during growth and an increase in secondary homothallism, i.e. oospore formation in the absence of the opposite mating type. The interaction can be considered mutualistic since these traits may increase the fitness of P. infestans in nature. Assays of biomarkers for cellular stress revealed that an Hsp70 chaperone was upregulated by PiERE1. A genome-wide search for more members of the Hsp70 family identified ten belonging to the DnaK subfamily, one in the Hsp110/SSE subfamily, and pseudogenes. Four DnaK subfamily genes encoding predicted cytoplasmic or endoplasmic reticulum proteins were upregulated in strains harbouring PiERE1. This may explain the greater thermotolerance conferred by the RNA element, and suggests that Hsp70 may be a useful biomarker for testing organisms for the cellular effects of symbiotic elements. PMID- 20360180 TI - Comorbidities in patients with primary Sjogren's syndrome: a registry-based case control study. AB - OBJECTIVE: Although multiple diseases associated with primary Sjogren's syndrome (pSS) have been reported, reliable data regarding the prevalence of specific medical comorbidities among patients with pSS remain sparse. We investigated the prevalence and risk for a broad spectrum of medical conditions among patients with pSS in Taiwan. METHODS: A total of 1974 patients with pSS were eligible for inclusion in the study group. We randomly selected 9870 enrollees matched with the study subjects, using the Taiwan National Health Insurance Research Dataset for 2006 and 2007, inclusive. Conditional logistic regression analyses conditioned on sex, age, monthly income, and level of urbanization of the patient's community were used to calculate the odds ratios (OR) of various comorbid conditions. RESULTS: Pearson chi-square tests revealed that patients with pSS had significantly higher prevalence of hyperlipidemia, cardiac arrhythmias, headaches, migraines, fibromyalgia (FM), asthma, pulmonary circulation disorders, hypothyroidism, liver disease, peptic ulcers, hepatitis B, deficiency anemias, depression, and psychoses. Conditional regression analyses showed that, compared to patients without the condition, patients with pSS were more likely to have hyperlipidemia (OR 1.42), cardiac arrhythmias (OR 1.32), headaches (OR 1.47), migraines (OR 1.86), FM (OR 1.71), asthma (OR 1.54), pulmonary circulation disorders (OR 1.42), hypothyroidism (OR 2.37), liver disease (OR 1.89), peptic ulcers (OR 1.88), hepatitis B (OR 2.34), deficiency anemias (OR 1.33), depression (OR 2.57), and psychoses (OR 2.15). CONCLUSION: The prevalence of several comorbidities was increased among the patients with pSS. Our study provides epidemiological data for comorbidities among pSS patients in an ethnic Chinese population. PMID- 20360181 TI - Observational studies of infections in rheumatoid arthritis: a metaanalysis of tumor necrosis factor antagonists. AB - OBJECTIVE: Published metaanalyses of tumor necrosis factor (TNF) antagonists and infection have focused on randomized controlled trials, which tend to have short duration, relatively small size, and stringent inclusion/exclusion criteria that may limit enrollment to patients at low risk of infection. We performed a systematic review and synthesis of observational studies of TNF antagonists and infection risk. METHODS: We conducted a systematic literature search of studies estimating overall risk of serious infection after anti-TNF exposure in rheumatoid arthritis (RA). We estimated a pooled relative risk (RR) for the relevant observational studies, using a random-effects model. RESULTS: Five cohort studies and 2 nested case-control studies were included in the metaanalysis. Anti-TNF therapy appeared to significantly increase risk of serious infection (pooled adjusted RR 1.37, 95% CI 1.18, 1.60). CONCLUSION: Our metaanalysis of observational data demonstrated an increased risk of serious infection in subjects with RA receiving anti-TNF therapy, versus those not receiving these agents. PMID- 20360182 TI - Outcomes of children treated for Lyme arthritis: results of a large pediatric cohort. AB - OBJECTIVE: Children often develop arthritis secondary to Lyme disease; however, optimal treatment of Lyme arthritis in pediatric patients remains ill-defined. We sought to characterize the outcomes of a large cohort of children with Lyme arthritis treated using the approach recommended by the American Academy of Pediatrics and the Infectious Diseases Society of America. METHODS: Medical records of patients with Lyme arthritis seen by rheumatologists at a tertiary care children's hospital from 1997 to 2007 were reviewed. Patients were classified with antibiotic responsive or refractory arthritis based on absence or presence of persisting joint involvement 3 months after antibiotic initiation. Treatment regimens and outcomes in patients with refractory arthritis were analyzed. RESULTS: Of 99 children with Lyme arthritis, 76 had arthritis that responded fully to antibiotics, while 23 developed refractory arthritis. Most patients with refractory arthritis were successfully treated with nonsteroidal antiinflammatory drugs (6 patients), intraarticular steroid injections (4), or disease-modifying antirheumatic drugs (DMARD) (2). Five were lost to followup. Six patients with refractory arthritis were initially treated elsewhere and received additional antibiotic therapy, with no apparent benefit. Three subsequently required DMARD, while 3 had gradual resolution of arthritis without further therapy. Antibiotic responsiveness could not be predicted from our clinical or laboratory data. CONCLUSION: Lyme arthritis in children has an excellent prognosis. More than 75% of referred cases resolved with antibiotic therapy. Of patients with antibiotic refractory arthritis, none in whom followup data were available developed chronic arthritis, joint deformities, or recurrence of infection, supporting current treatment guidelines. PMID- 20360184 TI - Reproducibility of joint swelling assessments in long-lasting rheumatoid arthritis: influence on Disease Activity Score-28 values (SEA-Repro study part I). AB - OBJECTIVES: To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score 28 (DAS28). METHODS: Seven healthcare professionals from different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen's kappa statistic. RESULTS: Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively. CONCLUSION: Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone. PMID- 20360185 TI - More night than day--circadian rhythms in polymyalgia rheumatica and ankylosing spondylitis. AB - The circadian rhythm of symptoms in patients with chronic inflammatory diseases is well known. Circadian rhythms could be used to identify targets for time adapted antiinflammatory therapies, which are administered prior to the flare of cytokine synthesis and inflammatory activity. In recent years, the diurnal variations in rheumatoid arthritis have been described precisely for pain, stiffness, and functional disability, as well as the underlying cyclic variations in hormone levels and cytokine concentrations. This review summarizes the current knowledge on circadian rhythms in other rheumatic diseases, focusing on polymyalgia rheumatica and ankylosing spondylitis. PMID- 20360183 TI - Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. AB - OBJECTIVE: To systematically review the literature on reported adverse effects (AE) associated with use of topical nonsteroidal antiinflammatory drugs (NSAID) in older adults with osteoarthritis (OA). METHODS: A systematic search of Medline (1950 to November 2009), Scopus, Embase, Web of Science, Cochrane databases, Dissertation and American College of Rheumatology meeting abstracts was performed to identify original randomized controlled trials, case reports, observational studies, editorials, or dissertations reporting AE from topical NSAID in older adults with OA. Information was sought on study and participant characteristics, detailed recording of application site, and systemic AE as well as withdrawals due to AE. RESULTS: The initial search yielded 953 articles of which 19 met eligibility criteria. Subjects receiving topical NSAID reported up to 39.3% application site AE, and up to 17.5% systemic AE. Five cases of warfarin potentiation with topical agents were reported, 1 resulting in gastrointestinal bleeding. In formal trials, the withdrawal rate from AE ranged from 0 to 21% in the topical agents, 0 to 25% in the oral NSAID, and 0 to 16% in the placebo group. CONCLUSION: Although topical NSAID are safer than oral NSAID (fewer severe gastrointestinal AE), a substantial proportion of older adults report systemic AE with topical agents. The withdrawal rate due to AE with topical agents is comparable to that of oral NSAID. Given the safety profile and withdrawal rates described in this study, further data are needed to determine the incremental benefits of topical NSAID compared to other treatment modalities in older adults with OA. PMID- 20360186 TI - Socioeconomic burden of psoriatic arthritis in Hong Kong: direct and indirect costs and the influence of disease pattern. AB - OBJECTIVE: To estimate the direct costs and indirect costs of patients with psoriatic arthritis (PsA) in Hong Kong. METHODS: A retrospective cost-of-illness study was performed on 125 patients with PsA. Participants completed questionnaires on demographics, employment status, and out of pocket expenses. Health resources consumption was recorded by chart review and patient self-report questionnaire. Patients were grouped according to disease pattern, i.e., peripheral and axial disease. Multiple regression was used to determine the predictors of the costs. RESULTS: The average annual direct costs were $4,141 (2006 US dollars) per patient. Costs of inpatient care accounted for 27% of direct costs, followed by costs of visits to healthcare providers (25%). The estimated average indirect costs were $3,127 per patient-year. Forty-eight (42%) patients had no indirect costs. Sixty percent of patients with peripheral disease were still employed, compared to 39% of patients with axial disease. Patients with axial disease had almost twice the indirect costs compared to those with peripheral disease (p = 0.005). Increased pain and poor function were independently associated with increased direct costs. Worse physical health status, determined by indirect costs borne by the patient, and poor function and old age predicted high costs. CONCLUSION: PsA imposes substantial economic burden. Pain and function are significantly associated with costs. Improvements in treatments to reduce pain and restore function are likely to reduce the costs incurred by these patients. PMID- 20360187 TI - Influence of STAT4 polymorphism in primary Sjogren's syndrome. AB - OBJECTIVE: To examine the influence of STAT4 rs7574865 gene polymorphism on patients with primary Sjogren's syndrome (SS). METHODS: Two different cohorts were studied: 69 patients with primary SS and 296 controls from Colombia and 108 patients with primary SS and 227 controls from Germany. Samples were genotyped for the STAT4 rs7574865 single-nucleotide polymorphism with a predesigned TaqMan single-nucleotide polymorphism genotyping assay. We carried out a metaanalysis of our results combined with data published to date. RESULTS: Although no significant differences were observed in the allele frequencies of STAT4 rs7574865 gene polymorphism between patients and controls in Colombians (p = 0.28, OR 1.24, 95% CI 0.82-1.87) and Germans (p = 0.08, OR 1.40, 95% CI 0.96 2.02), the metaanalysis disclosed a significant effect of the T allele on disease (p = 4.7 x 10(-6), OR 1.40, 95% CI 1.21-1.62). CONCLUSION: These data reinforce the influence of STAT4 gene on primary SS and as a general autoimmune gene. PMID- 20360188 TI - Estimating indirect costs in primary Sjogren's syndrome. AB - OBJECTIVE: To estimate the indirect costs associated with primary Sjogren's syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. METHODS: Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. RESULTS: Using a conservative model, the estimated total annual indirect costs (95% CI) were 7677 pound sterling (5560 pound sterling, 9794 pound sterling) for pSS, 10,444 pound sterling (8206 pound sterling, 12,681 pound sterling) for RA, and 892 pound sterling (307 pound sterling, 1478 pound sterling) for controls. Using a model that maximizes the estimates, the equivalent figures were 13,502 pound sterling (9542 pound sterling, 17,463 pound sterling), 17,070 pound sterling (13,112 pound sterling, 21,028 pound sterling), and 3382 pound sterling (2187 pound sterling, 4578 pound sterling), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group. CONCLUSION: pSS is associated with significantly increased indirect costs equivalent to 69%-83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS. PMID- 20360189 TI - Secondary Sjogren's syndrome in systemic lupus erythematosus defines a distinct disease subset. AB - OBJECTIVE: Sjogren's syndrome (SS) may occur in patients with systemic lupus erythematosus (SLE). We sought to determine whether the presence of SS in a large cohort of patients with SLE defines a subset with distinctive sociodemographic, clinical, and laboratory features. METHODS: The Johns Hopkins Lupus Cohort was divided into 2 groups, based on the presence or absence of SS, defined by the presence of an objective measure of sicca or an abnormal minor salivary gland biopsy in a patient with sicca symptoms. These groups were compared with regard to sociodemographic, clinical, and laboratory features. Multivariable logistic regression was then performed to adjust the findings for potential sociodemographic, clinical, and laboratory confounders. RESULTS: The 259 patients with SS (14% of the cohort), when compared with the 1531 patients without SS, were older at the time of SLE diagnosis and were more commonly women and white. Photosensitivity, oral ulcers, Raynaud's phenomenon, anti-Ro antibodies, and anti La antibodies had a significant positive association while renal disease, anti ribonucleoprotein (RNP) antibodies, and anti-dsDNA antibodies had a negative association with the presence of SS after adjustment for age (at last cohort visit), gender, ethnicity, and anti-Ro antibodies. The older age at diagnosis of SLE among the patients with SS did not remain a significant finding after adjustment for the age of the patient at last cohort visit. CONCLUSION: The subset of patients with SLE and SS has a distinct clinical and laboratory phenotype, with a higher frequency of older white women with photosensitivity, oral ulcers, Raynaud's phenomenon, anti-Ro antibodies, and anti-La antibodies and a lower frequency of renal disease, anti-dsDNA antibodies, and anti-RNP antibodies. PMID- 20360190 TI - Using magnetic resonance angiography to measure abnormal synovial blood vessels in early inflammatory arthritis: a new imaging biomarker? AB - OBJECTIVE: To ascertain whether magnetic resonance angiography (MRA) can reliably detect synovial neovascularization in subjects with early inflammatory arthritis. METHODS: Subjects with 6 weeks to 6 months of clinical evidence of inflammatory hand arthritis had a radiograph, power Doppler ultrasound (PDU) scan, magnetic resonance imaging (MRI), and contrast enhanced MRA performed on the more symptomatic hand. Ultrasound examination of the wrist and 2nd-5th metacarpophalangeal (MCP) joints was scored for erosions, synovial thickening, and synovial blood flow. MRI were assessed using the OMERACT Rheumatoid Arthritis MRI Score (RAMRIS). MRA was used to assess the number of abnormal vessels in the 2nd-5th MCP and in the wrist. RESULTS: Of 30 subjects, 66.7% showed abnormal vasculature on MRA in the MCP and/or wrist; mean number of abnormal vessels was 5.24 (range 0-22). Number of abnormal vessels on MRA was strongly correlated with degree of blood flow seen in the corresponding area on PDU (r = 0.79, p or=50 (range 0.81-0.96, median 0.91), a referral guideline (0.80-0.94, 0.92), and immunochemical faeces tests (0.70-1.00, 0.95). Of these, only specificity of the faeces tests was good. Specificity was consistently high for family history (0.75-0.98, 0.91), weight loss (0.72-0.96, 0.89), and iron deficiency anaemia (0.83-0.95, 0.92), but all tests lacked sensitivity. None of these six tests was (sufficiently) studied in primary care. CONCLUSIONS: Although combinations of symptom and results of immunochemical faeces tests showed good diagnostic performance for colorectal cancer, evidence from primary care is lacking. High quality studies on their role in the diagnostic investigation of colorectal cancer in primary care are urgently needed. PMID- 20360224 TI - Carbon cost of trials. What cost evidence synthesis? PMID- 20360225 TI - Doctors and assisted suicide. Do it properly or not at all. PMID- 20360227 TI - Harmless cuts in health care. Improve care for elderly people. PMID- 20360228 TI - Harmless cuts in health care. Right first time, every time. PMID- 20360229 TI - Clostridium difficile. Monoclonal antibody treatment. PMID- 20360231 TI - UTI in primary care. Midstream urine sampling is still helpful. PMID- 20360232 TI - Do not sit on the bed. For these good reasons. PMID- 20360236 TI - Generic drug debate. Norgine's reply to ABPI. PMID- 20360235 TI - Generic drug debate. ABPI supports generic concept. PMID- 20360237 TI - Open all hours primary care. Whose access problem? PMID- 20360238 TI - Open all hours primary care. Feathering the cuckoo's nest. PMID- 20360242 TI - Optimizing the tracking of falls in studies of older participants: comparison of quarterly telephone recall with monthly falls calendars in the MOBILIZE Boston Study. AB - Tracking falls among elders is challenging. In this reliability study, which took place between October 2007 and February 2008, the authors compared participants' daily recordings of falls on calendars with a telephone survey of recall of falls over the previous 3 months within the population-based MOBILIZE Boston Study cohort, a cohort of 765 elders. From the cohort, 218 participants were randomly selected. Falls were tracked prospectively on daily calendars (mailed back monthly). Telephone recalls of falls over the previous 3 months were conducted in January and February 2008. Agreement, sensitivity, and specificity were calculated to compare the occurrence of falls as determined by 3-month recall with falls recorded by daily calendar (gold standard) during the same 3-month period. Results showed good agreement between recall and calendars: 27 persons reported a fall by both methods. However, while the 3-month recall correctly classified persons who did not fall (164 persons by both methods), it missed 25% of participants who fell (of 36 participants with a calendar-reported fall, 9 did not report a fall by telephone recall). Kappa was 0.74 (95% confidence interval: 0.68, 0.80), sensitivity was 75%, and specificity was 96%. Retrospective 3-month recall of falls resulted in underreporting of falls by as much as 25% compared with daily calendars. Calendars should be considered the preferred method of ascertaining falls in longitudinal studies. PMID- 20360243 TI - Relation of immediate postnatal growth with obesity and related metabolic risk factors in adulthood: the northern Finland birth cohort 1966 study. AB - The authors examined associations between postnatal growth velocity through age 2 years and metabolic outcomes at age 31 years in a population-based birth-cohort study of 3,778 Finns (1966-1998). Approximately 8 height measurements and 9 weight measurements were obtained from birth to age 2 years. Peak height velocity (PHV) and peak weight velocity (PWV) in infancy were derived from parametric growth curves fitted to longitudinal height and weight growth data. Body mass index (BMI), waist circumference (WC), high density lipoprotein (HDL) cholesterol, triglycerides, glucose, systolic and diastolic blood pressure (BP), and the metabolic syndrome were measured at age 31 years. PHV was significantly positively associated with systolic and diastolic BP and WC in adulthood. For each 8-cm/year (2-standard-deviation) increase in PHV, WC increased by 1.60 cm (95% confidence interval: 0.73, 2.46), after adjustment for potential confounders, including birth weight. PWV was significantly associated with adulthood systolic BP, WC, and BMI. A 4-kg/year higher PWV was associated with a 1.87-cm (95% confidence interval: 1.08, 2.65) larger WC in adulthood, after adjustment for potential confounders. HDL cholesterol (direct), triglycerides (inverse), and metabolic syndrome (inverse) displayed associations with PWV only after BMI was accounted for. These results showed that growth during the immediate postnatal period is associated with adulthood obesity and BP. Lifestyle changes from early life might be important in reducing adulthood obesity and high BP risk. PMID- 20360244 TI - Community incidence of norovirus-associated infectious intestinal disease in England: improved estimates using viral load for norovirus diagnosis. AB - Existing estimates of the incidence of infectious intestinal disease (IID) caused by norovirus are based on electron microscopy or reverse transcription-polymerase chain reaction (RT-PCR). Neither method accurately represents norovirus disease burden: Electron microscopy has poor diagnostic sensitivity, and RT-PCR has poor diagnostic specificity. In this study, viral load measurements were used to identify cases of norovirus-associated IID and to produce new incidence estimates for England. IID cases were ascertained in the Study of Infectious Intestinal Disease in England (1993-1996), and stool specimens were tested by semiquantitative real-time RT-PCR for norovirus. The age-adjusted community incidence of norovirus-associated IID was 4.5/100 person-years (95% credibility interval: 3.8, 5.2), equating to 2 million episodes/year. Among children aged less than 5 years, the community incidence was 21.4/100 person-years (95% credibility interval: 15.9, 27.7), and the incidence of consultations to general practitioners for norovirus-associated IID was 3.2/100 person-years (95% credibility interval: 2.6, 3.8), with 100,000 children visiting their general practitioner for norovirus-associated IID each year. Norovirus is the most common cause of IID in the community in England and is responsible for a similar number of pediatric primary care consultations as rotavirus. PMID- 20360245 TI - Nerve growth factor promotes cardiac repair following myocardial infarction. AB - RATIONALE: Nerve growth factor (NGF) promotes angiogenesis and cardiomyocyte survival, which are both desirable for postinfarction myocardial healing. Nonetheless, the NGF potential for cardiac repair has never been investigated. OBJECTIVE: To define expression and localization of NGF and its high-affinity receptor TrkA (tropomyosin-related receptor A) in the human infarcted heart and to investigate the cardiac roles of both endogenous and engineered NGF using a mouse model of myocardial infarction (MI). METHODS AND RESULTS: Immunostaining for NGF and TrkA was performed on heart samples from humans deceased of MI or unrelated pathologies. To study the post-MI functions of endogenous NGF, a NGF neutralizing antibody (Ab-NGF) or nonimmune IgG (control) was given to MI mice. To investigate the NGF therapeutic potential, human NGF gene or control (empty vector) was delivered to the murine periinfarct myocardium. Results indicate that NGF is present in the infarcted human heart. Both cardiomyocytes and endothelial cells (ECs) possess TrkA, which suggests NGF cardiovascular actions in humans. In MI mice, Ab-NGF abrogated native reparative angiogenesis, increased EC and cardiomyocyte apoptosis and worsened cardiac function. Conversely, NGF gene transfer ameliorated EC and cardiomyocyte survival, promoted neovascularization and improved myocardial blood flow and cardiac function. The prosurvival/proangiogenic Akt/Foxo pathway mediated the therapeutic benefits of NGF transfer. Moreover, NGF overexpression increased stem cell factor (the c-kit receptor ligand) expression, which translated in higher myocardial abundance of c kit(pos) progenitor cells in NGF-engineered hearts. CONCLUSIONS: NGF elicits pleiotropic beneficial actions in the post-MI heart. NGF should be considered as a candidate for therapeutic cardiac regeneration. PMID- 20360246 TI - Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction. AB - RATIONALE: Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in beta cells. Although vascular TRPM3 mRNA has been reported, there is no knowledge of TRPM3 protein or its regulation and function in the cardiovascular system. OBJECTIVE: To determine the relevance and regulation of TRPM3 in vascular biology. METHODS AND RESULTS: TRPM3 expression was detected at mRNA and protein levels in contractile and proliferating vascular smooth muscle cells. Calcium entry evoked by pregnenolone sulfate or sphingosine was suppressed by TRPM3 blocking antibody or knock-down of TRPM3 by RNA interference. Low-level constitutive TRPM3 activity was also detected. In proliferating cells, channel activity was coupled negatively to interleukin-6 secretion via a calcium-dependent mechanism. In freshly isolated aorta, TRPM3 positively modulated contractile responses independently of L-type calcium channels. Concentrations of pregnenolone sulfate required to evoke responses were higher than the known plasma concentrations of the steroids, leading to a screen for other stimulators. beta-Cyclodextrin was one of few stimulators of TRPM3, revealing the channels to be partially suppressed by endogenous cholesterol, the precursor of pregnenolone. Elevation of cholesterol further suppressed channel activity and loading with cholesterol to generate foam cells precluded observation of TRPM3 activity. CONCLUSIONS: The data suggest functional relevance of TRPM3 in contractile and proliferating phenotypes of vascular smooth muscle cells, significance of constitutive channel activity, regulation by cholesterol, and potential value of pregnenolone sulfate in therapeutic vascular modulation. PMID- 20360247 TI - Effects of free immunoglobulin light chains on viral myocarditis. AB - RATIONALE: In recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis. Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation. OBJECTIVE: We studied the possible involvement of FLC in the pathogenesis of viral myocarditis, and therapeutic effects of FLC using an animal model of viral myocarditis. METHODS AND RESULTS: DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis (EMC) virus. Serum levels and concentrations in the heart of kappa FLC on day 14 in mice inoculated with EMC virus were significantly increased compared with controls. Myocardial viral concentration was significantly inhibited, the area of myocardial lesions was smaller in mice treated with kappa or lambda FLC, and survival of mice given FLC significantly improved. In contrast, an FLC antagonist deteriorated myocarditis. kappa and lambda FLC chains inhibited EMC viral replication in human amnion cells in vitro. lambda FLC significantly increased the gene expression of interleukin-10 in the heart which was previously shown to improve viral myocarditis when given exogenously. FLC also tended to increase the gene expressions of interferon-alpha and -gamma in the heart mice. CONCLUSIONS: FLC have antiviral and antiinflammatory effects and improved viral myocarditis in mice. FLC may be promising agents for the treatment of viral myocarditis. PMID- 20360248 TI - Deep mRNA sequencing for in vivo functional analysis of cardiac transcriptional regulators: application to Galphaq. AB - RATIONALE: Transcriptional profiling can detect subclinical heart disease and provide insight into disease etiology and functional status. Current microarray based methods are expensive and subject to artifact. OBJECTIVE: To develop RNA sequencing methodologies using next generation massively parallel platforms for high throughput comprehensive analysis of individual mouse cardiac transcriptomes. To compare the results of sequencing- and array-based transcriptional profiling in the well-characterized Galphaq transgenic mouse hypertrophy/cardiomyopathy model. METHODS AND RESULTS: The techniques for preparation of individually bar-coded mouse heart RNA libraries for Illumina Genome Analyzer II resequencing are described. RNA sequencing showed that 234 high-abundance transcripts (>60 copies/cell) comprised 55% of total cardiac mRNA. Parallel transcriptional profiling of Galphaq transgenic and nontransgenic hearts by Illumina RNA sequencing and Affymetrix Mouse Gene 1.0 ST arrays revealed superior dynamic range for mRNA expression and enhanced specificity for reporting low-abundance transcripts by RNA sequencing. Differential mRNA expression in Galphaq and nontransgenic hearts correlated well between microarrays and RNA sequencing for highly abundant transcripts. RNA sequencing was superior to arrays for accurately quantifying lower-abundance genes, which represented the majority of the regulated genes in the Galphaq transgenic model. CONCLUSIONS: RNA sequencing is rapid, accurate, and sensitive for identifying both abundant and rare cardiac transcripts, and has significant advantages in time- and cost efficiencies over microarray analysis. PMID- 20360250 TI - The constitutive function of native TRPC3 channels modulates vascular cell adhesion molecule-1 expression in coronary endothelial cells through nuclear factor kappaB signaling. AB - RATIONALE: Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent, on expression and function of the Ca(2+)-permeable channel transient receptor potential canonical (TRPC)3, regardless of the ability of the stimulatory signal to induce regulated Ca(2+) influx, leading to the hypothesis that TRPC3 constitutive, rather than regulated function, contributes to the underlying signaling mechanism. OBJECTIVE: The present studies addressed this important question and gathered mechanistic insight on the signaling coupling constitutive TRPC3 function to VCAM-1 expression. METHODS AND RESULTS: In HCAECs, maneuvers that prevent Ca(2+) influx or knockdown of TRPC3 markedly reduced tumor necrosis factor (TNF)alpha-induced VCAM-1 and monocyte adhesion. TNFalpha also induced TRPC3 expression and TRPC3-mediated constitutive cation influx and currents. Stable (HEK293 cells) or transient (HCAECs) overexpression of TRPC3 enhanced TNFalpha-induced VCAM-1 compared to wild-type cells. IkappaBalpha phosphorylation/degradation was reduced by TRPC3 knockdown and increased by channel overexpression. Inhibition of calmodulin completely prevented nuclear factor kappaB activation, whereas blocking calmodulin-dependent kinases or NADPH oxidases rendered partial inhibition. CONCLUSIONS: Our findings indicate that in HCAECs expression of VCAM-1 and monocyte adhesion depend, to a significant extent, on TRPC3 constitutive function through a signaling mechanism that requires constitutive TRPC3-mediated Ca(2+) influx for proper activation of nuclear factor kappaB, presumably through Ca(2+)-dependent activation of the calmodulin/calmodulin-dependent kinase axis. PMID- 20360249 TI - Nox4 is a novel inducible source of reactive oxygen species in monocytes and macrophages and mediates oxidized low density lipoprotein-induced macrophage death. AB - RATIONALE: The enhanced formation of intracellular reactive oxygen species (ROS) induced by oxidized low-density lipoprotein (OxLDL) promotes macrophage death, a process likely to contribute to the formation of necrotic cores and the progression of atherosclerotic lesions. Yet macrophage deficiency of phagocytic NADPH oxidase (Nox2), the primary source of ROS in macrophages, does not reduce atherosclerotic lesion development in mice. This suggests an as yet unidentified NADPH oxidase may be present in macrophages and responsible for the intracellular ROS formation induced by OxLDL. OBJECTIVE: The aim of this study was to identify the source of intracellular ROS involved in macrophage death. METHODS AND RESULTS: Nox4 was expressed in human monocytes and mature macrophages, and was localized to the endoplasmic reticulum and to defined foci within the nucleus. Nox4 colocalized with p22(phox), and both proteins were upregulated in response to OxLDL stimulation, whereas Nox2/gp91(phox) levels remained unchanged. Induction of Nox4 expression, intracellular ROS formation and macrophage cytotoxicity induced by OxLDL were blocked by MEK1/2 inhibition, but not by inhibitors of p38-MAPK (mitogen-activated protein kinase), JNK (Jun N-terminal kinase), or JAK2 (Janus kinase 2). Small interfering RNA knockdown of Nox4 inhibited both intracellular ROS production and macrophage cytotoxicity induced by OxLDL, whereas Nox4 overexpression enhanced both OxLDL-stimulated ROS formation and macrophage death. CONCLUSIONS: Nox4 is a novel source of intracellular ROS in human monocytes and macrophages. Induction of Nox4 by OxLDL is mediated by the MEK1/ERK pathway and required for OxLDL cytotoxicity in human macrophages, implicating monocytic Nox4 in atherogenesis. PMID- 20360251 TI - Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival. AB - RATIONALE: The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation. OBJECTIVE: The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated. METHODS AND RESULTS: Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal regulated kinases 1 and 2. CONCLUSIONS: These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival. PMID- 20360252 TI - Lysophosphatidic acid receptors LPA1 and LPA3 promote CXCL12-mediated smooth muscle progenitor cell recruitment in neointima formation. AB - RATIONALE: The chemokine CXCL12 (CXC motif ligand 12) and its receptor CXCR 4 (CXC motif receptor 4) direct the recruitment of smooth muscle progenitor cells (SPCs) in neointima formation after vascular injury. Lysophosphatidic acid (LPA) induces CXCL12 and neointimal accumulation of smooth muscle cells (SMCs) in uninjured arteries. Thus, we hypothesize that LPA may regulate CXCL12-mediated vascular remodelling. OBJECTIVES: We evaluated the role of LPA receptors in initiating CXCL12-dependent vascular repair by SPCs. METHODS AND RESULTS: Wire induced carotid injury was performed in apolipoprotein E(-/-) mice on western type diet. LPA receptor expression was studied by immunostaining and quantitative RT-PCR. LPA receptors LPA(1) and LPA(3) were detected in the media of uninjured arteries and in the injury-induced neointima. LPA(3) mRNA was upregulated and LPA(1) mRNA downregulated at one week after injury. The LPA(1/3) antagonist Ki16425 inhibited neointima formation by 71% and reduced both relative neointimal SMCs and the macrophage content. Additionally, neointimal hypoxia-inducible factor-1alpha and CXCL12 expression, the injury-induced peripheral stem cell antigen-1 (Sca-1)(+)/Lin(-) SPC mobilization, and the neointimal recruitment of Sca-1(+)SMCs were inhibited by Ki16425. In wild type mice, LPA20:4 increased CXCL12 and hypoxia-inducible factor-1alpha expression in carotid arteries as early as 1 day following short-term endoluminal incubation. LPA20:4-induced SPC mobilization and neointima formation were blocked by Ki16425, LPA(1)- and LPA(3) specific small interfering (si)RNA, and the CXCR4 antagonist POL5551. Ki16425 reduced LPA20:4-mediated neointimal recruitment of SPC as demonstrated by 2 photon microscopy in bone marrow chimeric mice after repopulation with SM22-LacZ transgenic, hematopoietic cells. Moreover, POL5551 decreased the neointimal accumulation of CXCR4(+) SMCs. CONCLUSIONS: LPA(1) and LPA(3) promote neointima formation through activation of CXCL12-mediated mobilization and recruitment of SPCs. PMID- 20360253 TI - Manipulation of death pathways in desmin-related cardiomyopathy. AB - RATIONALE: Transgenic mice with cardiac specific overexpression of mutated alphaB crystallin (CryAB(R120G)) display Desmin-related myopathy (DRM) with dilated cardiomyopathy and heart failure. Our previous studies showed the presence of progressive mitochondrial abnormalities and activation of apoptotic cell death in CryAB(R120G) transgenic hearts. However, the role of mitochondrial dysfunction and apoptosis in the overall course of the disease was unclear. OBJECTIVE: We tested the hypothesis that prevention of apoptosis would ameliorate CryAB(R120G) pathology and decrease morbidity. METHODS AND RESULTS: We crossed CryAB(R120G) mice to transgenic mice with cardiac specific overexpression of Bcl-2. Sustained Bcl-2 overexpression in CryAB(R120G) hearts prolonged CryAB(R120G) transgenic mice survival by 20%. This was associated with decreased mitochondrial abnormalities, restoration of cardiac function, prevention of cardiac hypertrophy, and attenuation of apoptosis. CryAB(R120G) misfolded protein aggregation was significantly reduced in the double transgenic. However, inhibition of apoptotic signaling resulted in the upregulation of autophagy and alternative death pathways, the net result being increased necrosis. CONCLUSION: Although Bcl-2 overexpression prolonged life in this DRM model, in the absence of apoptosis, another death pathway was activated. PMID- 20360254 TI - TRB3 function in cardiac endoplasmic reticulum stress. AB - RATIONALE: Tribbles (TRB)3 is an intracellular pseudokinase that modulates the activity of several signal transduction cascades. TRB3 has been reported to inhibit the activity of Akt protein kinases. TRB3 gene expression is highly regulated in many cell types, and amino acid starvation, hypoxia, or endoplasmic reticulum (ER) stress promotes TRB3 expression in noncardiac cells. OBJECTIVE: The objective of this work was to examine TRB3 expression and function in cultured cardiac myocytes and in mouse heart. METHODS AND RESULTS: Agents that induced ER stress increased TRB3 expression in cultured cardiac myocytes while blocking insulin-stimulated Akt activation in these cells. Knockdown of TRB3 in cultured cardiac myocytes reversed the effects of ER stress on insulin signaling. Experimental myocardial infarction led to increased TRB3 expression in murine heart tissue in the infarct border zone suggesting that ER stress may play a role in pathological cardiac remodeling. Transgenic mice with cardiac-specific overexpression of TRB3 were generated and they exhibited normal contractile function but altered cardiac signal transduction and metabolism with reduced cardiac glucose oxidation rates. Transgenic TRB3 mice were also sensitized to infarct expansion and cardiac myocyte apoptosis in the infarct border zone after myocardial infarction. CONCLUSIONS: These results demonstrate that TRB3 induction is a significant aspect of the ER stress response in cardiac myocytes and that TRB3 antagonizes cardiac glucose metabolism and cardiac myocyte survival. PMID- 20360255 TI - Regulation of cardiomyocyte polyploidy and multinucleation by CyclinG1. AB - RATIONALE: Polyploidy and multinucleation are characteristic features of mammalian cardiomyocytes, which develop shortly after birth when most differentiated cardiomyocytes become acytokinetic. Cardiac overload and hypertrophy further increase the degree of polyploidy of cardiomyocytes, suggesting a role in cell type-specific responses to physiological and pathological stimuli. OBJECTIVE: We sought to study the function of cyclinG1 in the regulation of polyploidy and multinucleation in cardiomyocytes. METHODS AND RESULTS: We found that expression of cyclinG1, a transcriptional target of p53, coincides with arrest of cardiomyocyte proliferation and onset of polyploidization. Overexpression of cyclinG1 promoted DNA synthesis but inhibited cytokinesis in neonatal cardiomyocytes leading to an enlarged population of binuclear cardiomyocytes. Reciprocally, inactivation of the cyclinG1 gene in mice lowered the degree of polyploidy and multinucleation in cardiomyocytes. Moreover, lack of cyclinG1 prevented the increase of polynucleated cardiomyocytes in response to pressure overload and hypertrophy. CONCLUSIONS: CyclinG1 is an important player for the regulation of polyploidy and multinucleation in cardiomyocytes probably by inhibition of apoptosis caused by checkpoint activation. PMID- 20360256 TI - Glycogen synthase kinase-3beta regulates post-myocardial infarction remodeling and stress-induced cardiomyocyte proliferation in vivo. AB - RATIONALE: Numerous studies have proposed that glycogen synthase kinase (GSK) 3beta is a central regulator of the hypertrophic response of cardiomyocytes. However, all of this work has relied on overexpression of GSK-3beta, expression of constitutively active mutants, or small molecule inhibitors with documented off-target effects. Genetic loss of function approaches have not been used in the adult mouse because germ-line deletion of GSK-3beta is embryonic-lethal. OBJECTIVE: This study was designed to define the role played by GSK-3beta in pressure overload (PO)-induced hypertrophy and remodeling following myocardial infarction (MI). METHODS AND RESULTS: We used a mouse model that allows inducible, cardiomyocyte-specific deletion of GSK-3beta in the adult knockout. Surprisingly, we find that knockout mice exposed to PO induced by thoracic aortic constriction exhibit a normal hypertrophic response. Thus, in contrast to virtually all prior published studies, GSK-3beta appears to play at most a minor role in the hypertrophic response to PO stress. However, GSK-3beta does regulate post-MI remodeling because the GSK-3beta knockouts had less left ventricular dilatation and better-preserved left ventricular function at up to 8 weeks post MI despite demonstrating significantly more hypertrophy in the remote myocardium. Deletion of GSK-3beta also led to increased cardiomyocyte proliferation following PO and MI. CONCLUSIONS: Deletion of GSK-3beta protects against post-MI remodeling and promotes stress-induced cardiomyocyte proliferation in the adult heart. These studies suggest that inhibition of GSK-3beta could be a strategy to both prevent remodeling and to promote cardiac regeneration in pathological states. PMID- 20360257 TI - Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis. AB - RATIONALE: Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein (LDL). OBJECTIVE: We explored putative links between apoM and very-low-density (VLDL)/LDL metabolism and the antiatherogenic potential of apoM in vivo. METHODS AND RESULTS: Plasma apoM was increased approximately 2.1 and approximately 1.5 fold in mice lacking LDL receptors (Ldlr(-/-)) and expressing dysfunctional LDL receptor-related protein 1 (Lrp1(n2/n2)), respectively, but was unaffected in apoE-deficient (ApoE(-/-)) mice. Thus, pathways controlling catabolism of VLDL and LDL affect plasma apoM. Overexpression (approximately 10-fold) of human apoM increased (50% to 70%) and apoM deficiency decreased ( approximately 25%) plasma VLDL/LDL cholesterol in Ldlr(-/-) mice, whereas apoM did not affect plasma VLDL/LDL in mice with intact LDL receptors. Moreover, plasma clearance of apoM-enriched VLDL/LDL was slower than that of control VLDL/LDL in mice lacking functional LDL receptors and LRP1, suggesting that apoM impairs the catabolism of VLDL/LDL that occurs independently of the LDL receptor and LRP1. ApoM overexpression decreased atherosclerosis in ApoE(-/-) (60%) and cholate/cholesterol-fed wild-type mice (70%). However, in Ldlr(-/-) mice the antiatherogenic effect of apoM was attenuated by its VLDL/LDL-raising effect. CONCLUSION: The data suggest that defect LDL receptor function leads to increased plasma apoM concentrations, which in turn, impairs the removal of VLDL/LDL from plasma. This mechanism opposes the otherwise antiatherogenic effect of apoM. PMID- 20360258 TI - The national free delivery and caesarean policy in Senegal: evaluating process and outcomes. AB - This article presents the results of an evaluation of the free delivery and caesarean policy (FDCP) in Senegal. The policy was introduced into five poor regions in 2005 and in 2006 was extended at regional hospital level to all regions apart from the capital (Dakar). The evaluation was carried out in 2006-7. There were four research components, all focused on selected facilities and districts within the five FDCP regions: a financial analysis of expenditure on the policy and wider health financing in the five regions and nationally; 54 key informant interviews from national down to facility level; 10 focus group discussions and 8 in-depth interviews; and analysis based on clinical record extraction of 761 major obstetric interventions. The evaluation found significant implementation difficulties, especially related to the allocation of funds and kits and the adequacy of their contents. Despite that, significant increases in utilization in normal deliveries (from 40% to 44% of expected deliveries in FDCP areas over 2004-5) and in caesarean rates (rising from 4.2% to 5.6% in FDCP areas) were recorded. National data suggested that these trends were not found in non-FDCP regions. Using the evaluation data, the cost per additional caesarean under the policy was US$467 and the cost per additional supervised normal delivery was US$21. The article concludes that, in order to achieve its full potential, the FDCP requires improved systems for planning and allocating resources, and new channels to reimburse lower level facilities. It is also important that all complicated deliveries (not just caesareans) are included in the package. In the case of Senegal, a complementary strategy of investment in facilities, transportation and staffing is required to bring greater geographical access and upgrade services. These findings are likely to be relevant to other countries currently experimenting with similar approaches to reducing financial barriers to skilled attendance at delivery. PMID- 20360259 TI - Another addition to our article portfolio: announcing Brief UltraRapid Communications. PMID- 20360260 TI - Joseph Goldstein and Michael Brown: demoting egos, promoting success. Interview by Ruth Williams. PMID- 20360261 TI - MicroRNAs and heart failure diagnosis: MiR-acle or MiR-age? PMID- 20360262 TI - Regulation of myoendothelial junction formation: bridging the gap. PMID- 20360263 TI - Cold war battle against hot atherosclerotic plaques. PMID- 20360264 TI - Down but not out: candidate gene-based studies still have value in a world dominated by whole genome approaches. PMID- 20360266 TI - Comparative gene expression analysis of susceptible and resistant near-isogenic lines in common wheat infected by Puccinia triticina. AB - Gene expression after leaf rust infection was compared in near-isogenic wheat lines differing in the Lr10 leaf rust resistance gene. RNA from susceptible and resistant plants was used for cDNA library construction. In total, 55 008 ESTs were sequenced from the two libraries, then combined and assembled into 14 268 unigenes for further analysis. Of these ESTs, 89% encoded proteins similar to (E value of < or =10(-5)) characterized or annotated proteins from the NCBI non redundant database representing diverse molecular functions, cellular localization and biological processes based on gene ontology classification. Further, the unigenes were classified into susceptible and resistant classes based on the EST members assembled from the respective libraries. Several genes from the resistant sample (14-3-3 protein, wali5 protein, actin-depolymerization factor and ADP-ribosylation factor) and the susceptible sample (brown plant hopper resistance protein, caffeic acid O-methyltransferase, pathogenesis-related protein and senescence-associated protein) were selected and their differential expression in the resistant and susceptible samples collected at different time points after leaf rust infection was confirmed by RT-PCR analysis. The molecular pathogenicity of leaf rust in wheat was studied and the EST data generated made a foundation for future studies. PMID- 20360265 TI - Emerging anticancer therapeutic targets and the cardiovascular system: is there cause for concern? AB - The race for a cure to cancer continues, fueled by unprecedented discoveries of fundamental biology underlying carcinogenesis and tumorigenesis. The expansion of the target list and tools to approach them is moving the oncology community extraordinarily rapidly to clinical trials, bringing new hope for cancer patients. This effort is also propelling biological discoveries in cardiovascular research, because many of the targets being explored in cancer play fundamental roles in the heart and vasculature. The combined efforts of cardiovascular and cancer biologists, along with clinical investigators in these fields, will be needed to understand how to safely exploit these efforts. Here, we discuss a few of the many research foci in oncology where we believe such collaboration will be particularly important. PMID- 20360268 TI - A novel construction of genome space with biological geometry. AB - A genome space is a moduli space of genomes. In this space, each point corresponds to a genome. The natural distance between two points in the genome space reflects the biological distance between these two genomes. Currently, there is no method to represent genomes by a point in a space without losing biological information. Here, we propose a new graphical representation for DNA sequences. The breakthrough of the subject is that we can construct the moment vectors from DNA sequences using this new graphical method and prove that the correspondence between moment vectors and DNA sequences is one-to-one. Using these moment vectors, we have constructed a novel genome space as a subspace in R(N). It allows us to show that the SARS-CoV is most closely related to a coronavirus from the palm civet not from a bird as initially suspected, and the newly discovered human coronavirus HCoV-HKU1 is more closely related to SARS than to any other known member of group 2 coronavirus. Furthermore, we reconstructed the phylogenetic tree for 34 lentiviruses (including human immunodeficiency virus) based on their whole genome sequences. Our genome space will provide a new powerful tool for analyzing the classification of genomes and their phylogenetic relationships. PMID- 20360267 TI - Mutation@A Glance: an integrative web application for analysing mutations from human genetic diseases. AB - Although mutation analysis serves as a key part in making a definitive diagnosis about a genetic disease, it still remains a time-consuming step to interpret their biological implications through integration of various lines of archived information about genes in question. To expedite this evaluation step of disease causing genetic variations, here we developed Mutation@A Glance (http://rapid.rcai.riken.jp/mutation/), a highly integrated web-based analysis tool for analysing human disease mutations; it implements a user-friendly graphical interface to visualize about 40,000 known disease-associated mutations and genetic polymorphisms from more than 2600 protein-coding human disease causing genes. Mutation@A Glance locates already known genetic variation data individually on the nucleotide and the amino acid sequences and makes it possible to cross-reference them with tertiary and/or quaternary protein structures and various functional features associated with specific amino acid residues in the proteins. We showed that the disease-associated missense mutations had a stronger tendency to reside in positions relevant to the structure/function of proteins than neutral genetic variations. From a practical viewpoint, Mutation@A Glance could certainly function as a 'one-stop' analysis platform for newly determined DNA sequences, which enables us to readily identify and evaluate new genetic variations by integrating multiple lines of information about the disease-causing candidate genes. PMID- 20360269 TI - Roadblock ahead. PMID- 20360270 TI - Law & psychiatry: Genetic discrimination in mental disorders: the impact of the genetic information nondiscrimination act. AB - Genetics is one of the most active areas of research on mental disorders. As genetic tests related to psychiatric disorders and their treatments proliferate in research and clinical settings, the possibility becomes more troubling that such information will be used for purposes other than those for which it was collected. Because of this, the federal Genetic Information Nondiscrimination Act of 2008 is of substantial importance to persons with mental disorders, persons at risk for the conditions, and family members of both groups. This column discusses the process of passing the legislation, along with the implications of the act. PMID- 20360271 TI - Best practices: Best practices for improving engagement of clients in clinic care. AB - Mental health clinicians and program administrators must implement effective strategies for engaging and retaining clients in care. At a recent series of forums open to providers from clinics in New York City that was sponsored by the city and state public mental health authorities, high-performing providers described their client engagement strategies. In this column the effective strategies reported are summarized in four areas: the first session, staff training and expertise, productivity measures, and engaging families and support persons. The approaches should be of use to administrators to improve programs' ability to engage and retain clients in community-based clinic care. PMID- 20360272 TI - State mental health policy: Physical health screening in state mental health clinics: the New York health indicators initiative. AB - The New York State Office of Mental Health recently mandated that all adult outpatient clinics regularly monitor three health indicators--body mass index, blood pressure, and smoking status. After the population was defined, medical equipment was distributed. Regular training and quality improvement meetings were held to improve the electronic database for indicator data. Clinical directors were provided regular feedback on performance monitoring. Learning collaboratives allowed sharing of implementation strategies. After only four months of this coordinated effort, approximately 7,500 people with mental illnesses had been screened for the three health indicators across New York State. PMID- 20360273 TI - Provision of mental health services in U.S. nursing homes, 1995-2004. AB - OBJECTIVE: This study tracked the ability of U.S. nursing homes to provide on site mental health services after the Omnibus Budget Reconciliation Act (OBRA) of 1987 mandated the detection and treatment of mental illness among nursing home patients. The study also determined cross-sectional correlates of service availability and models of services. METHODS: Retrospective analyses were done using National Nursing Home Surveys from 1995, 1997, 1999, and 2004 (the most recent survey). The surveys are periodically conducted by the Centers for Disease Control and Prevention and represent the nation's approximately 17,000 nursing homes. The longitudinal trend of mental health service provision was analyzed for all facilities and for subgroups of facilities. Multivariate regression determined facility and geographic correlates in 2004. RESULTS: Roughly 80% of facilities provided on-site mental health services each survey year. In 2004, 25% of facilities provided mental health services regularly or at routinely scheduled times (regular basis), 24% provided them in an on-call manner (or as needed), and 28% provided them on both a regular and on-call basis. The remaining 22% of facilities provided no on-site mental health services. Multivariate analyses found that largest facilities (> or = 200 beds) were more able than small facilities (< 100 beds) to serve persons with mental illness (odds ratio=3.80, p=.024); compared with their counterparts, facilities were more likely to provide on-site services if they had a larger proportion of residents covered by Medicare or Medicaid programs, were in the Northeast region, or were in metropolitan areas. Similar correlates were found when the types of service provision models (regular basis, on-call basis, both a regular and on-call basis) were examined. CONCLUSIONS: The overall availability of nursing home-based mental health services did not improve over time during the post-OBRA era. Service availability is more problematic for certain facilities, such as small or rural ones. Financial, regulatory, and system-level efforts are needed to address this issue. PMID- 20360274 TI - Recent changes in the prevalence of psychiatric disorders among VA nursing home residents. AB - OBJECTIVE: This study identified recent changes in the prevalence of psychiatric disorders among Department of Veterans Affairs (VA) nursing home residents. METHODS: Psychiatric diagnoses in administrative databases were summarized for nursing home residents in 1998, 2002, and 2006. Census prevalence rates were compared with findings from earlier VA nursing home surveys. Prevalence rates were compared for age groups and birth cohorts of VA nursing home admissions in 1998 (N=27,734) and 2006 (N=32,543). RESULTS: Among residents in the census samples, prevalence rates for dementia and schizophrenia fluctuated moderately from 1990 to 2006, depression prevalence increased sharply, alcohol use disorder prevalence declined, and drug use disorder prevalence increased. Among 1998 and 2006 admissions, dementia prevalence increased for most birth cohorts but declined for most age groups (35% to 32% overall). Depression prevalence increased for all age groups and birth cohorts (27% to 37% overall), as did posttraumatic stress disorder prevalence (5% to 12% overall). Serious mental illness prevalence increased among the oldest residents and birth cohorts (19% to 22% overall). Alcohol use disorder prevalence declined for all birth cohorts and most age groups (18% to 16% overall), but drug use disorder prevalence increased substantially for younger age groups (6% to 9% overall). CONCLUSIONS: Examining differences in prevalence between birth cohorts and age groups can clarify trends in nursing home resident characteristics and improve projections of their future needs. PMID- 20360275 TI - Racial and ethnic disparities in use of psychotherapy: evidence from U.S. national survey data. AB - OBJECTIVE: This study investigated racial and ethnic disparities in psychotherapy use and expenditures in the United States and identified important factors associated with these disparities. METHODS: Using the Medical Expenditure Panel Survey from 1996 to 2006, the investigators performed bivariate and multivariable analyses to estimate racial and ethnic disparities in the probability of receiving any psychotherapy, total psychotherapy expenditures, and out-of-pocket payment share for 7,376 patients with depressive or anxiety disorders. Blinder Oaxaca decomposition techniques were used to identify the most important factors associated with these disparities. RESULTS: Caucasians were more likely to use psychotherapy than Latinos (57% versus 52%, p<.001), but there was no significant difference between Caucasians and African Americans in the probability of receiving any psychotherapy. Caucasians self-paid 29% of the total cost for each visit, significantly higher than the shares paid by Latinos (19%) and African Americans (14%). Racial-ethnic differences in the propensity to utilize psychotherapy vanished in multivariable regression, but Caucasians still paid a significantly higher out-of-pocket share than others. English proficiency was the most important factor associated with racial-ethnic disparities in psychotherapy use. The extensive Medicaid coverage among Latinos and African Americans was the main reason for their lower out-of-pocket payment for psychotherapy compared with Caucasians. CONCLUSIONS: This study found little evidence of racial and ethnic disparities in access to psychotherapy services. Health care reforms affecting mental health coverage under Medicaid would significantly affect psychotherapy expenditure and use among Latinos and African Americans. PMID- 20360276 TI - Stigma and depression treatment utilization among Latinos: utility of four stigma measures. AB - OBJECTIVES: Stigma associated with mental illness is an important yet understudied issue among Latinos. This study examined the psychometric properties of four stigma measures with a sample of Spanish-speaking Latino primary care patients. The study evaluated the scale for Perceived Discrimination Devaluation (PDD), the Stigma Concerns About Mental Health Care (SCMHC) scale, the Latino Scale for Antidepressant Stigma (LSAS), and the Social Distance (SD) scale. METHODS: Participants (N=200) were low-income Latinos who were screened for depression with the Patient Health Questionnaire (PHQ-2) and asked about their depression treatment history, and they completed the four stigma measures at two time points (25 and 30 months from baseline). The four stigma measures were examined for internal consistency, convergent validity, construct validity, and criterion-related validity. RESULTS: The factor-analytic results generally provided support for the construct validity of the measures. The four stigma measures also demonstrated internal consistency between two time points. Patients who reported greater social distance from individuals with depression were more likely to have been receiving treatment for emotional care in the past three months (odds ratio [OR]=.70, p<.05). Also, Latinos who scored high on the SCMHC (OR=.64, p<.05) and LSAS (OR=.77, p<.05) were less likely to have been taking antidepressant medications. CONCLUSIONS: The SCMHC, LSAS, and SD scales received support for their reliability and construct validity. Results also showed some support for their criterion-related validity. A more mixed picture emerged for the PDD. Stigma ratings were associated with depression treatment utilization. Stigma ratings changed over time and were associated with treatment experiences. PMID- 20360277 TI - Medication preferences and adherence among individuals with severe mental illness and psychiatric advance directives. AB - OBJECTIVE: Psychiatric advance directives allow patients with severe mental illness to document their preferences for particular medications. This study investigated the role of psychiatric advance directives in treatment choice and medication adherence. METHODS: A total of 123 persons with severe mental illness recorded medication preferences in psychiatric advance directives. The authors compared medication preferences to prescribed medications over 12 months, determined concordance between preferred and prescribed medications, and examined the effect of concordance on medication adherence at 12 months. RESULTS: Participants requested a median of two medications in their psychiatric advance directives (range from zero to six) and refused a median of one medication (range from zero to ten). Between baseline and follow-up there was a 27% increase in the number of medications prescribed that had been requested on the psychiatric advance directive (Wilcoxon matched pairs, p<.001). After correction for the number of medications listed in the psychiatric advance directive, a 10% increase in concordance remained significant (p<.001). Being prescribed at least one medication requested in the psychiatric advance directive predicted higher medication adherence at 12 months, after the analysis controlled for relevant covariates (odds ratio=7.8, 95% confidence interval=1.8-34.0). CONCLUSIONS: Providing information about medication preferences in psychiatric advance directives may increase prescribing of patient-preferred medications even in noncrisis settings. Patients who were prescribed medications that they requested in advance were significantly more likely to adhere to medications, supporting the benefit of patient participation in medication choice. Psychiatric advance directives appear to be a clinically useful conduit for communicating patient medication preferences. PMID- 20360278 TI - Pregnancy-related discontinuation of antidepressants and depression care visits among Medicaid recipients. AB - OBJECTIVE: This study examined whether pregnancy is associated with discontinuation of care for depression among low-income women. METHODS: Medicaid claims data from all 50 states were used in a matched cohort study design. The study included 3,237 women who gave birth between 1999 and 2000 and received depression treatment (antidepressant medications or a depression care visit) before initiating prenatal care. A control cohort of nonpregnant women receiving gynecologic care in the same period was matched by demographic and depression treatment characteristics. RESULTS: Prepregnancy, the antidepressant use rate was 66%. During pregnancy, antidepressant use dropped to 27% in the pregnant cohort compared with 62% in the control group (rate ratio [RR] =.44, 95% confidence interval [CI]=.41-.46) and remained low postpartum compared with the control group (35% versus 48%, RR=.74, CI=.70-.78). Similarly, depression care visits during the pregnancy period were reduced to 31% among the pregnant cohort compared with 49% for the control group (RR=.65, CI=.61-.69) and remained lower postpartum relative to the control group (24% versus 31%, RR=.78, CI=.73-.85). Interactions with pregnancy status were found for race-ethnicity and receipt of cash assistance from Medicaid. White women in the pregnancy cohort had a greater reduction in depression care visits than nonwhite women during the pregnancy period but less reduction in antidepressant use postpartum relative to the control group. Cash assistance was associated with less discontinuation in depression care visits postpartum compared with the control group (p<.05). CONCLUSIONS: Pregnancy was associated with discontinuation of any depression care among women receiving Medicaid; care did not resume postpartum. Race-ethnicity and Medicaid cash benefit status moderated this finding. Efforts are needed to mitigate these reductions. PMID- 20360279 TI - Pharmacotherapy of alcohol use disorders in the Veterans Health Administration. AB - OBJECTIVE: Acamprosate, oral and long-acting injectable naltrexone, and disulfiram are approved for treatment of alcohol dependence. Their availability and consideration of their use in treatment are now standards of high-quality care. This study determined rates of medication initiation among Veterans Health Administration (VHA) patients. METHODS: VHA pharmacy and administrative data were used to identify patients with alcohol use disorder diagnoses in fiscal years (FY) 2006 and 2007 and the proportion (nationally and by facility) who received each medication. Patient characteristics associated with receipt were also examined. RESULTS: Among more than a quarter-million patients with alcohol use disorder diagnoses, the percentage receiving any of the medications increased from 2.8% in FY 2006 to 3.0% in FY 2007. Receipt of these medications was more likely among patients who received specialty addiction care, those with alcohol dependence (compared with abuse), those younger than 55 years, and females. In the patient subgroups examined, the largest proportion to receive any of the medications was 11.6%. Across 128 VHA facilities, rates of use among patients in the sample who had received past-year specialty addiction treatment ranged from 0% to 20.5%; rates ranged from 0% to 4.3% among those with no specialty treatment. Patient preferences and medical contraindications could not be determined from the data. CONCLUSIONS: Findings suggest the need to better understand systemwide variation in use of these medications and their use as a rough proxy for availability and consideration of pharmacotherapy--a standard of care with strong organizational support. PMID- 20360280 TI - Consequences of receipt of a psychiatric diagnosis for completion of college. AB - OBJECTIVE: The purpose of this study was to evaluate the independent associations between DSM-IV psychiatric disorders and the failure to complete college among college entrants. METHODS: Data were from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The sample included 15,800 adults, aged 22 years and older, who at least entered college. Diagnoses were made with the NESARC survey instrument, the Alcohol Use Disorder and Associated Disability Interview Schedule-DSM-IV Version. The large sample permitted analysis of multiple psychiatric disorders in the same multivariable logistic regression models. Given the frequent comorbidity of these disorders, this approach is an important step toward disentangling the independent roles of disorders in postsecondary educational outcomes. RESULTS: Evaluation of the independent associations between specific psychiatric disorders and postsecondary educational attainment showed that five diagnoses were positively and significantly associated with the failure to graduate from college. Four were axis I diagnoses: bipolar I disorder, marijuana use disorder, amphetamine use disorder, and cocaine use disorder. One was an axis II diagnosis: antisocial personality disorder. CONCLUSIONS: This study provides new data on DSM-IV diagnoses associated with the failure to complete postsecondary education. The findings suggest that psychiatric factors play a significant role in college academic performance, and the benefits of prevention, detection, and treatment of psychiatric illness may therefore include higher college graduation rates. PMID- 20360281 TI - Simplifying adherence in schizophrenia. AB - Treatment nonadherence is a formidable challenge in today's clinical practice. Despite decades of focused research, medication adherence continues to be a significant risk factor for poor prognosis in schizophrenia. Studies demonstrate that no single strategy is effective for all patients and that a multidisciplinary approach customized to the patient's individual needs results in improved adherence rates. This Open Forum presents a comprehensive model for organizing and incorporating current and future evidence-based strategies with a focus on educational strategies, psychotherapeutic techniques, and a strong therapeutic alliance. PMID- 20360282 TI - Jail administrators' perceptions of the use of psychiatric advance directives in jails. AB - OBJECTIVE: Individuals with serious mental illnesses are at high risk of incarceration. Jails are often unable to obtain information needed to provide appropriate care. Psychiatric advance directives may be useful tools to communicate treatment information to jails. This study explored their use as a novel intervention for individuals with mental illnesses in jails. METHODS: Eighty jail administrators in North Carolina were surveyed to determine their support for psychiatric advance directives in jails. Relationships between respondents' job type (jail administrator or medical administrator) or jail census and support for the directives were examined by using chi square tests. Open-ended responses were analyzed using qualitative methods. RESULTS: Seventy three percent of respondents indicated they supported psychiatric advance directives. Respondents from jails at or below a median census of 120 were significantly more likely to support psychiatric advance directives than those from larger jails. CONCLUSIONS: Psychiatric advance directives' informational function may prove valuable in jail settings. Additional research assessing directives as interventions for individuals with mental illnesses at risk of incarceration is needed. PMID- 20360283 TI - Utilization of emergency medical transports and hospital admissions among persons with behavioral health conditions. AB - OBJECTIVE: Emergency medical services transport and emergency department misuse among persons with behavioral health conditions is a concern. Administrative data were used to examine medical transports and hospital admissions among persons with behavioral health conditions. METHODS: Data on 70,126 medical transports to emergency departments in three southeastern counties were analyzed. RESULTS: Compared with general medical transports, fewer behavioral health transports resulted in a hospital admission. Among behavioral health transports, persons with schizophrenia were 2.62 times more likely than those with substance use disorders to be admitted, and persons with mood disorders were 4.36 times more likely than those with substance use disorders to be admitted. Also, among behavioral health transports, rural transports were less likely than more urban transports to result in a hospital admission. CONCLUSIONS: More training of emergency medical services personnel and more behavioral health crisis resources, especially targeting rural areas and substance use disorders, are needed. PMID- 20360284 TI - Parenting with success and satisfaction among parents with severe mental illness. PMID- 20360285 TI - Employment for persons with borderline personality disorder. PMID- 20360287 TI - Recovery and the medical model in institutional care. PMID- 20360288 TI - 31-year-old man with fever, palpitations, and generalized rash. PMID- 20360289 TI - Rheumatology practice at Mayo Clinic: the first 40 years-1920 to 1960. PMID- 20360290 TI - Emergency department assessment of acute-onset chest pain: contemporary approaches and their consequences. PMID- 20360291 TI - Computed tomographic coronary artery calcium assessment for evaluating chest pain in the emergency department: long-term outcome of a prospective blind study. AB - OBJECTIVE: To determine the long-term outcome of computed tomographic (CT) quantification of coronary artery calcium (CAC) used as a triage tool for patients presenting with chest pain to an emergency department (ED). PATIENTS AND METHODS: Patients (men aged 30-62 years and women aged 30-65 years) with chest pain and low-to-moderate probability of coronary artery disease underwent both conventional ED chest pain evaluation and CT CAC assessment prospectively. Patients' physicians were blinded to the CAC results. The results of the conventional evaluation were compared with CAC findings on CT, and the long-term outcome in patients undergoing CT CAC assessment was established. Primary end points (acute coronary syndrome, death, fatal or nonfatal non-ST-segment elevation myocardial infarction, fatal or nonfatal ST-segment elevation myocardial infarction) and secondary outcomes (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, coronary stenting, or a combination thereof) were obtained when the patient was dismissed from the ED or hospital and then at 30 days, 1 year, and 5 years. RESULTS: Of the 263 study patients, 133 (51%) had a CAC score of zero. This absence of CAC correlated strongly with the likelihood of noncardiac chest pain. Among 133 patients with a CAC score of zero, only 1 (<1%) had cardiac chest pain. Conversely, of the 31 patients shown to have cardiac chest pain, 30 (97%) had evidence of CAC on CT. When a CAC cutoff score of 36 was used, as suggested by receiver operating characteristic analysis, sensitivity was 90%; specificity, 85%; positive predictive value, 44%; and negative predictive value, 99%. During long-term follow-up, patients without CAC experienced no cardiac events at 30 days, 1 year, and 5 years. CONCLUSION: Findings suggest that CT CAC assessment is a powerful adjunct in chest pain evaluation for the population at low-to-intermediate risk. Absent or minimal CAC in this population makes cardiac chest pain extremely unlikely. The absence of CAC suggests an excellent long-term (5-year) prognosis, with no primary or secondary cardiac outcomes occurring in study patients at 5 year follow-up. PMID- 20360292 TI - In-hospital major clinical outcomes in patients with chronic renal insufficiency presenting with acute coronary syndrome: data from a Registry of 8176 patients. AB - OBJECTIVE: To assess the impact of chronic renal insufficiency (CRI) on in hospital major adverse cardiac events across the acute coronary syndrome (ACS) spectrum. PATIENTS AND METHODS: From January 29, 2007, through July 29, 2007, 6 adjacent Middle Eastern countries participated in the Gulf Registry of Acute Coronary Events, a prospective, observational registry of 8176 patients. Patients were categorized according to estimated glomerular filtration rate into 4 groups: normal (>or=90 mL/min), mild (60-89 mL/min), moderate (30-59 mL/min), and severe CRI (<30 mL/min). Patients' characteristics and in-hospital major adverse cardiac events in the 4 groups were analyzed. RESULTS: Of 6518 consecutive patients with ACS, 2828 (43%) had mild CRI, 1304 (20%) had moderate CRI, and 345 (5%) had severe CRI. In CRI groups, patients were older and had a higher prevalence of hypertension, diabetes mellitus, and dyslipidemia. On admission, these patients had a higher resting heart rate and frequently had atypical and delayed presentations. Compared with the normal estimated glomerular filtration group, CRI groups were less likely to receive antiplatelet drugs, beta-blockers, angiotensin-converting enzyme inhibitors, and statins and were less likely to undergo coronary angiography. In-hospital heart failure, cardiogenic shock, and major bleeding episodes were significantly higher in all CRI groups. In multivariate analysis, mild, moderate, and severe CRI were associated with a higher adjusted odds ratio (OR) of death (mild: OR, 2.1; 95% confidence interval [CI], 1.2-3.7; moderate: OR, 6.7; 95% CI, 3.9-11.5; and severe: OR, 12.0; 95% CI, 6.6-21.7). CONCLUSION: Across the ACS spectrum, patients with CRI had a worse risk profile, had more atypical and delayed presentations, and were less likely to receive evidence-based therapy. Chronic renal insufficiency of varying stages is an independent predictor of in-hospital morbidity and mortality. PMID- 20360293 TI - Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. AB - The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice. However, safety concerns, especially regarding hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis, in which liver enzyme levels are elevated in the absence of proven hepatotoxicity. This class effect is usually asymptomatic, reversible, and dose-related. However, the increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment in patients with high cardiovascular risk. These diseases result in abnormally high liver biochemistry values, discouraging statin use by clinicians, fostering treatment discontinuation, and leaving a large number of at-risk patients untreated. A PubMed/MEDLINE search of the literature regarding statin safety (January 1, 1994 December 31, 2008) was performed, using the following search terms: statin safety, statin-related hepatotoxicity, and chronic liver disease and statin use, as well as the specific names of different statins and different liver diseases. Relevant clinical trials, review articles, panel discussions, and guideline recommendations were selected. This review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions. For each patient, the decision should be based on an individual assessment of risks and benefits. PMID- 20360294 TI - Responsible use of computed tomography in the evaluation of coronary artery disease and chest pain. AB - Many options are available to clinicians for the noninvasive evaluation of the cardiovascular system and patient concerns about chest discomfort. Cardiac computed tomography (CT) is a rapidly advancing field of noninvasive imaging. Computed tomography incorporates coronary artery calcium scoring, coronary angiography, ventricular functional analysis, and information about noncardiac thoracic anatomy. We searched the PubMed database and Google from inception to September 2009 for resources on the accuracy, risk, and predictive capacity of coronary artery calcium scoring and CT coronary angiography and have reviewed them herein. Cardiac CT provides diagnostic information comparable to echocardiography, nuclear myocardial perfusion imaging, positron emission tomography, and magnetic resonance imaging. A cardiac CT study can be completed in minutes. In patients with a nondiagnostic stress test result, cardiac CT can preclude the need for invasive angiography. Prognostic information portends excellent outcomes in patients with normal study results. Use of cardiac CT can reduce health care costs and length of emergency department stays for patients with chest pain. Cardiac CT examination provides clinically relevant information at a radiation dose similar to well-established technologies, such as nuclear myocardial perfusion imaging. Advances in technique can reduce radiation dose by 90%. With appropriate patient selection, cardiac CT can accurately diagnose heart disease, markedly decrease health care costs, and reliably predict clinical outcomes. PMID- 20360296 TI - Screening and brief intervention for underage drinkers. AB - In a 2007 report, the US Surgeon General called for health care professionals to renew efforts to reduce underage drinking. Focusing on the adolescent patient, this review provides health care professionals with recommendations for alcohol related screening, brief intervention, and referral to treatment. MEDLINE and published reviews were used to identify relevant literature. Several brief screening methods have been shown to effectively identify underage drinkers likely to have alcohol use disorders. After diagnostic assessment when germane, the initial intervention typically focuses on education, motivation for change, and consideration of treatment options. Internet-accessible resources providing effective brief interventions are available, along with supplemental suggestions for parents. Recent changes in federal and commercial insurance reimbursement policies provide some fiscal support for these services, although rate increases and expanded applicability may be required to prompt the participation of many practitioners. Nevertheless, advances in clinical methods and progress on reimbursement policies have made screening and brief intervention for underage drinking more feasible in general health care practice. PMID- 20360295 TI - A "hot" topic in dyslipidemia management--"how to beat a flush": optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention. AB - Niacin is the most effective lipid-modifying agent for raising high-density lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of English-language literature from January 1, 1985, through April 7, 2009. This search used the title keywords niacin or nicotinic acid crossed with the Medical Subject Headings adverse effects and human. Niacin flushing is a receptor-mediated, mainly prostaglandin D(2)-driven phenomenon, the frequency, onset, and duration of which are largely determined by the distinct pharmacological and metabolic profiles of different niacin formulations. Subjective assessments include ratings of redness, warmth, itching, and tingling. In clinical trials, most (>60%) niacin users experienced mild or moderate flushing, which tended to decrease in frequency and severity with continued niacin treatment, even with advancing doses. Approximately 5% to 20% of patients discontinued treatment because of flushing. Flushing may be minimized by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (alcohol or hot beverages), and taking 325 mg of aspirin 30 minutes before niacin dosing. The current review advocates an initially slow niacin dose escalation from 0.5 to 1.0 g/d during 8 weeks and then from 1.0 to 2.0 g in a single titration step (if tolerated). Through effective counseling, treatment prophylaxis with aspirin, and careful dose escalation, adherence to niacin treatment can be improved significantly. Wider implementation of these measures should enable higher proportions of patients to reach sufficient niacin doses over time to prevent cardiovascular events. PMID- 20360297 TI - 38-Year-old woman with increasing fatigue and dyspnea. PMID- 20360298 TI - Possible link between apical ballooning syndrome during anaphylaxis and inappropriate administration of epinephrine. PMID- 20360299 TI - Possible link between apical ballooning syndrome during anaphylaxis and inappropriate administration of epinephrine-1. PMID- 20360300 TI - Radiation therapy for gynecomastia. PMID- 20360301 TI - Vectorial transport of nucleoside analogs from the apical to the basolateral membrane in double-transfected cells expressing the human concentrative nucleoside transporter hCNT3 and the export pump ABCC4. AB - The identification of the transport proteins responsible for the uptake and the efflux of nucleosides and their metabolites enables the characterization of their vectorial transport and a better understanding of their absorption, distribution, and elimination. Human concentrative nucleoside transporters (hCNTs/SLC28A) are known to mediate the transport of natural nucleosides and some nucleoside analogs into cells in a sodium-dependent and unidirectional manner. On the other hand, several human multidrug resistance proteins [human ATP-binding cassette transporter, subfamily C (ABCC)] cause resistance against nucleoside analogs and mediate transport of phosphorylated nucleoside derivatives out of the cells in an ATP-dependent manner. For the integrated analysis of uptake and efflux of these compounds, we established a double-transfected Madin-Darby canine kidney (MDCK) II cell line stably expressing the human uptake transporter hCNT3 in the apical membrane and the human efflux pump ABCC4 in the basolateral membrane. The direction of transport was from the apical to the basolateral compartment, which is in line with the unidirectional transport and the localization of both recombinant proteins in the MDCKII cells. Recombinant hCNT3 mediated the transport of several known nucleoside substrates, and we identified 5-azacytidine as a new substrate for hCNT3. It is of interest that coexpression of both transporters was confirmed in pancreatic adenocarcinomas, which represent an important clinical indication for the therapeutic use of nucleoside analogs. Thus, our results establish a novel cell system for studies on the vectorial transport of nucleosides and their analogs from the apical to the basolateral compartment. The results contribute to a better understanding of the cellular transport characteristics of nucleoside drugs. PMID- 20360302 TI - Transporter studies with the 3-O-sulfate conjugate of 17alpha-ethinylestradiol: assessment of human liver drug transporters. AB - 17alpha-Ethinylestradiol (EE2), a component of oral contraceptives, is known to undergo considerable first-pass 3-O-sulfation in the intestine and liver. Once formed, the 3-O-sulfate conjugate (EE2-Sul) is detected in circulation at appreciable levels (versus parent EE2) and is present in bile. Therefore, hepatic uptake of EE2-Sul was assessed with suspensions of cryopreserved human primary hepatocytes. In this instance, there was evidence for active (temperature dependent) uptake, which was described by a two-K(m) (Michaelis constant) model (K(m1) = 220 nM; K(m2) = 15.5 microM). Uptake was inhibited (approximately 90%) by bromosulfophthalein but not by tetraethylammonium or p-aminohippurate. In agreement, EE2-Sul was shown to be a substrate of recombinant organic anion transporter peptides (OATP1B1 and OATP2B1), and Na(+)/taurocholate-cotransporting polypeptide (NTCP), expressed individually in human embryonic kidney (HEK) 293 cells. Transport by OATP1B1 was described by two K(m) values (87 nM and 141 microM), whereas OATP2B1- and NTCP-mediated uptake into HEK-293 cells conformed to single K(m) kinetics (10.7 and 2.6 microM, respectively). EE2-Sul was also assessed as an efflux transporter substrate using membrane vesicles expressing bile salt export pump, breast cancer resistance protein (BCRP), and individual forms of multidrug resistance-associated protein (MRP1, MRP2, and MRP3). Transport studies were also conducted with a cell line expression P-glycoprotein. Only vesicles that contained BCRP exhibited ATP-dependent uptake of EE2-Sul (K(m1) = 2.9 and K(m2) = 307 microM). Collectively, the data show that hepatic uptake of EE2-Sul can be mediated by three transporters (OATP1B1, OATP2B1, and NTCP), whereas biliary excretion of EE2-Sul into bile likely involves BCRP. PMID- 20360303 TI - Transporter studies with the 3-O-sulfate conjugate of 17alpha-ethinylestradiol: assessment of human kidney drug transporters. AB - 17alpha-Ethinylestradiol (EE2), a synthetic and potent estrogen receptor agonist, is extensively metabolized in both intestine and liver and is largely excreted in bile and urine as the 3-O-sulfate (EE2-Sul) and 3-O-glucuronide. In the present study, EE2-Sul was evaluated as a substrate of various transporters known to be expressed in the kidney. Uptake studies were performed with human epithelial cells [human embryonic kidney (HEK)-293] that contained individually expressed organic cation transporter 2 (OCT2), organic anion transporter (OAT) forms 3 and 4, and multidrug and toxin extrusion 1 (MATE1). The transporter phenotyping studies were extended to include insect cell (Sf9) membrane vesicles that expressed multidrug resistance-associated protein 4 (MRP4) and Madin-Darby canine kidney cells that expressed OAT1. Based on the results obtained, we concluded that EE2-Sul serves as a substrate of OAT3 and OAT4, but not OCT2, OAT1, MATE1, and MRP4. First, EE2-Sul uptake was highly increased in OAT3/HEK-293 cells (versus mock/HEK-293 cells) and was inhibited by OAT3 inhibitors such as bromosulfophthalein (BSP), cimetidine, and probenecid. OAT3-mediated uptake also conformed to single-K(m) (Michaelis constant) kinetics (K(m) = 21.1 microM). Second, EE2-Sul uptake was also significantly higher in OAT4/HEK-293 cells and was inhibited by BSP, methotrexate, and probenecid. In contrast to OAT3, OAT4 dependent uptake was characterized by a two-K(m) model (K(m1) = 1.6 microM; K(m2) = 195 microM). Based on the results of this study, we hypothesize that EE2-Sul is taken up into renal proximal tubule cells by OAT3, and OAT4 plays a role in its secretion into the renal brush border lumen. PMID- 20360304 TI - The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain. AB - Disrupted-in-schizophrenia 1 (DISC1) has been genetically associated with schizophrenia, and with brain phenotypes including grey matter volume and working memory performance. However, the molecular and cellular basis for these associations remains to be elucidated. One potential mechanism may be via an altered interaction of DISC1 with its binding partners. In this context, we previously demonstrated that one DISC1 variant, Leu607Phe, influenced the extent of centrosomal localization of pericentriolar material 1 (PCM1) in SH-SY5Y cells. The current study extends this work to human brain, and includes another DISC1 coding variant, Ser704Cys. Using immunohistochemistry, we first characterized the distribution of PCM1 in human superior temporal gyrus (STG). PCM1 immunoreactivity was localized to the centrosome in glia, but not in neurons, which showed widespread immunoreactivity. We quantified centrosomal PCM1 immunoreactivity in STG glia of 81 controls and 67 subjects with schizophrenia, genotyped for the two polymorphisms. Centrosomal PCM1 immunoreactive area was smaller in Cys704 carriers than in Ser704 homozygotes, with a similar trend in Phe607 homozygotes compared with Leu607 carriers, replicating the finding in SH SY5Y cells. No differences were seen between controls and subjects with schizophrenia. These findings confirm in vivo that DISC1 coding variants modulate centrosomal PCM1 localization, highlight a role for DISC1 in glial function and provide a possible cellular mechanism contributing to the association of these DISC1 variants with psychiatric phenotypes. Whether this influence of DISC1 genotype extends to other centrosomal proteins and DISC1 binding partners remains to be determined. PMID- 20360305 TI - Transcriptome analysis and molecular signature of human retinal pigment epithelium. AB - Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed 'signature' genes by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 RPE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of RPE signature genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the RPE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that RPE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The RPE signature gene set should allow the validation of RPE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases. PMID- 20360306 TI - Charting new territory by simulated modeling of a clinical trial. PMID- 20360307 TI - Evidence of extraordinary growth in the progressive enlargement of renal cysts. AB - BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease, cysts derived from tubules are detected at birth by ultrasound (threshold for detection >7.0 mm); thus, fetal cyst growth rates must exceed 2300%/yr. In adults, the combined renal cyst component enlarges at approximately 12%/yr by growth of individual cysts. To explore this discrepancy, the growth rates of individual cysts were determined in adult polycystic kidneys. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Diameter, volume, and growth rates of individual cysts were measured by magnetic resonance in 30 individual cysts in three adult patients over a span of 3 years. Results were confirmed in 22 cysts measured in five patients by computed tomography over a span of 11 years. RESULTS: Mean cyst diameters were 20.4 +/- 9.9 mm (range 7.1 to 40.5 mm) at baseline and 25.8 +/- 15.6 mm (range 7.8 to 49.6 mm) after 3 years. Mean cyst volumes, determined by manual segmentation and summation of magnetic resonance cross sections, were 8.7 +/- 12.9 cm(3) (0.3 to 43.3 cm(3)) and 24.2 +/- 66.3 cm(3) (0.3 to 364.8 cm(3)) after 3 years. Mean cyst growth rates ranged from 6.9 to 23.9%/yr; the maximum growth rate was 71.1%/yr, far less than required to develop a 7-mm diameter cyst in utero. Results were similar in 22 cysts examined by computed tomography. CONCLUSIONS: It was concluded that renal cysts detected by ultrasound in newborns must have grown at exuberant rates in utero; thereafter, expansion appears to proceed at much slower rates. PMID- 20360308 TI - The TRbeta-selective agonist, GC-1, stimulates mitochondrial oxidative processes to a lesser extent than triiodothyronine. AB - Specific tissue responses to thyroid hormone are mediated by the hormone binding to two subtypes of nuclear receptors, TRalpha and TRbeta. We investigated the relationship between TRbeta activation and liver oxidative metabolism in hypothyroid rats treated with equimolar doses of triiodothyronine (T(3)) and GC 1, a TRbeta agonist. T(3) treatment produces increases in O(2) consumption and H(2)O(2) production higher than those elicited by GC-1. The greater effects of T(3) on oxidative processes are linked to the higher hormonal stimulation of the content of respiratory chain components including autoxidizable electron carriers as demonstrated by the measurement of activities of respiratory complexes and H(2)O(2) generation in the presence of respiratory inhibitors. It is conceivable that these differential effects are dependent on the inability of GC-1 to stimulate TRalpha receptors that are likely involved in the expression of some components of the respiratory chain. The greater increases in reactive oxygen species production and susceptibility to oxidants exhibited by mitochondria from T(3)-treated rats are consistent with their higher lipid and protein oxidative damage and lower resistance to Ca(2)(+) load. The T(3) and GC-1 effects on the expression levels of nuclear respiratory factor-1 and -2 and peroxisome proliferator-activated receptor-gamma coactivator-1alpha suggest the involvement of respiratory factors in the agonist-linked changes in mitochondrial respiratory capacities and H(2)O(2) production. PMID- 20360309 TI - Macula densa sensing and signaling mechanisms of renin release. AB - Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release. Renin is the rate-limiting step in the activation of the renin-angiotensin system, a key modulator of body fluid homeostasis. Here, we discuss recent advances in understanding macula densa sensing and suggest these cells, in addition to salt, also sense various chemical and metabolic signals in the tubular environment that directly trigger renin release. PMID- 20360310 TI - Targeted deletion of Dicer from proximal tubules protects against renal ischemia reperfusion injury. AB - MicroRNAs are endogenous, noncoding, small RNAs that regulate expression and function of genes, but little is known about regulation of microRNA in the kidneys under normal or pathologic states. Here, we generated a mouse model in which the proximal tubular cells lack Dicer, a key enzyme for microRNA production. These mice had normal renal function and histology under control conditions despite a global downregulation of microRNAs in the renal cortex; however, these animals were remarkably resistant to renal ischemia-reperfusion injury (IRI), showing significantly better renal function, less tissue damage, lower tubular apoptosis, and improved survival compared with their wild-type littermates. Microarray analysis showed altered expression of specific microRNAs during renal IRI. Taken together, these results demonstrate evidence for a pathogenic role of Dicer and associated microRNAs in renal IRI. PMID- 20360312 TI - Uremic thrombocytopathy is not about urea. AB - Platelet dysfunction in renal failure is attributable to high levels of small, partly dialyzable molecules known as uremic toxins, hence the term "uremic thrombocytopathy." Although a variety of moieties contribute to platelet dysfunction or abnormal interactions between platelets and the vascular wall, urea remains a potential factor. Here, we studied three family members with familial azotemia, a rare autosomal dominant syndrome characterized by high plasma urea resulting from impaired urinary excretion but normal renal function otherwise. Platelet function, assessed in vitro and by traditional bleeding time, was normal in all individuals. Abnormal platelet function in patients with renal failure is not caused by high concentrations of urea. PMID- 20360311 TI - ATF3-mediated epigenetic regulation protects against acute kidney injury. AB - A variety of stress stimuli, including ischemia-reperfusion (I/R) injury, induce the transcriptional repressor ATF3 in the kidney. The functional consequences of this upregulation in ATF3 after renal I/R injury are not well understood. Here, we found that ATF3-deficient mice had higher renal I/R-induced mortality, kidney dysfunction, inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin), and apoptosis compared with wild type mice. Furthermore, gene transfer of ATF3 to the kidney rescued the renal I/R induced injuries in the ATF3-deficient mice. Molecular and biochemical analysis revealed that ATF3 interacted directly with histone deacetylase 1 (HDAC1) and recruited HDAC1 into the ATF/NF-kappaB sites in the IL-6 and IL-12b gene promoters. The ATF3-associated HDAC1 deacetylated histones, which resulted in the condensation of chromatin structure, interference of NF-kappaB binding, and inhibition of inflammatory gene transcription after I/R injury. Taken together, these data demonstrate epigenetic regulation mediated by the stress-inducible gene ATF3 after renal I/R injury and suggest potential targeted approaches for acute kidney injury. PMID- 20360313 TI - Hydrogen sulfide inhibits plasma renin activity. AB - The development of renovascular hypertension depends on the release of renin from the juxtaglomerular (JG) cells, a process regulated by intracellular cAMP. Hydrogen sulfide (H2S) downregulates cAMP production in some cell types by inhibiting adenylyl cyclase, suggesting the possibility that it may modulate renin release. Here, we investigated the effect of H2S on plasma renin activity and BP in rat models of renovascular hypertension. In the two-kidney-one-clip (2K1C) model of renovascular hypertension, the H2S donor NaHS prevented and treated hypertension. Compared with vehicle, NaHS significantly attenuated the elevation in plasma renin activity and angiotensin II levels but did not affect plasma angiotensin-converting enzyme activity. Furthermore, NaHS inhibited the upregulation of renin mRNA and protein levels in the clipped kidneys of 2K1C rats. In primary cultures of renin-rich kidney cells, NaHS markedly suppressed forskolin-stimulated renin activity in the medium and the intracellular increase in cAMP. In contrast, NaHS did not affect BP or plasma renin activity in normal or one-kidney-one-clip (1K1C) rats, both of which had normal plasma renin activity. In conclusion, these results demonstrate that H2S may inhibit renin activity by decreasing the synthesis and release of renin, suggesting its potential therapeutic value for renovascular hypertension. PMID- 20360314 TI - Prevalence of incompletely penetrant Huntington's disease alleles among individuals with major depressive disorder. AB - OBJECTIVE: Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established. METHOD: This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression. RESULTS: CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats. CONCLUSIONS: In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles. PMID- 20360316 TI - Automatic and strategic representation of the self in major depression: trait and state abnormalities. AB - OBJECTIVE: Dysfunctional negative thoughts about the self have long been hypothesized to reflect mood-independent cognitive vulnerability for major depressive disorder. These thoughts are believed to be predominantly automatic, in that they are involuntary and hard to inhibit. However, existing empirical evidence provides limited support for this theory, instead emphasizing the role of intentional ruminative (i.e., effortful) thoughts. To help clarify this theoretical controversy and investigate biased processing of emotional self referent information in major depression, the authors utilized event-related brain potentials, which are used to index neural engagement during specific stages of cognitive processing. METHOD: The P2 and late positive event-related brain components were examined during a free recall task in patients with current (N=17) or remitted (N=18) major depression and healthy comparison subjects (N=17). Participants made judgments on whether a word described them (self referential condition) or former U.S. President Bill Clinton (other-referential condition). RESULTS: Healthy comparison subjects and subjects with remitted, but not current, major depression demonstrated enhanced recall of positive self referent items. Greater component amplitudes in response to negative relative to positive self-referent items were evident in individuals with current and remitted major depression during the automatic processing stage (indexed by the P2 component) and in individuals with current depression during effortful encoding (indexed by the late positive component). CONCLUSIONS: Observed mood independent abnormalities in automatic processing and mood-dependent abnormalities in effortful processing of emotional self-referent information provide direct support for an integrative theory of cognitive dysfunction in major depression, which amalgamates two main, but largely competing, theories of the disorder. PMID- 20360315 TI - Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. AB - OBJECTIVE: The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs. METHOD: High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial. RESULTS: Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. A set of 72 a priori-selected candidate genes did not show pharmacogenetic associations above a chance level, but an association with response to escitalopram was detected in the interleukin-6 gene, which is a close homologue of IL11. CONCLUSIONS: While limited statistical power means that a number of true associations may have been missed, these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates. Genome-wide studies, if properly replicated, may thus be important steps in the elucidation of the genetic basis of pharmacological response. PMID- 20360317 TI - Efficacy and safety of long-term fluoxetine versus lithium monotherapy of bipolar II disorder: a randomized, double-blind, placebo-substitution study. AB - OBJECTIVE: The authors examined the safety and efficacy of long-term fluoxetine monotherapy, lithium monotherapy, and placebo therapy in preventing relapse and recurrence of bipolar type II major depressive episode. The authors hypothesized that fluoxetine monotherapy would be superior to lithium monotherapy with a similar hypomanic mood conversion rate. METHOD: Patients at least 18 years old who recovered from their major depressive episode during initial open-label fluoxetine monotherapy were randomly assigned to receive 50 weeks of double-blind monotherapy with fluoxetine at 10-40 mg/day, lithium at 300-1200 mg/day, or placebo. The primary outcome measure was time to relapse or recurrence. Secondary outcome measures included the proportion of patients remaining well and the frequency of hypomanic symptoms. RESULTS: There were no significant differences in clinical or demographic characteristics among the fluoxetine (N=28), lithium (N=26), and placebo (N=27) groups. The mean time to relapse was 249.9 days for the fluoxetine group, 156.4 days for the lithium group, and 186.9 days for the placebo group. The hazard of relapse was significantly lower with fluoxetine compared with lithium, and the estimated hazard of relapse with lithium was 2.5 times greater than with fluoxetine. There were no statistically significant or clinically meaningful differences in hypomanic symptoms among treatment groups over time. One patient taking fluoxetine and one patient taking placebo discontinued treatment because of hypomania. CONCLUSIONS: These findings suggest that long-term fluoxetine monotherapy may provide superior relapse-prevention benefit relative to lithium monotherapy after recovery from bipolar II major depressive episode without an increase in hypomanic mood conversion episodes. PMID- 20360318 TI - Emotion modulation in PTSD: Clinical and neurobiological evidence for a dissociative subtype. AB - In this article, the authors present evidence regarding a dissociative subtype of PTSD, with clinical and neurobiological features that can be distinguished from nondissociative PTSD. The dissociative subtype is characterized by overmodulation of affect, while the more common undermodulated type involves the predominance of reexperiencing and hyperarousal symptoms. This article focuses on the neural manifestations of the dissociative subtype in PTSD and compares it to those underlying the reexperiencing/hyperaroused subtype. A model that includes these two types of emotion dysregulation in PTSD is described. In this model, reexperiencing/hyperarousal reactivity is viewed as a form of emotion dysregulation that involves emotional undermodulation, mediated by failure of prefrontal inhibition of limbic regions. In contrast, the dissociative subtype of PTSD is described as a form of emotion dysregulation that involves emotional overmodulation mediated by midline prefrontal inhibition of the same limbic regions. Both types of modulation are involved in a dynamic interplay and lead to alternating symptom profiles in PTSD. These findings have important implications for treatment of PTSD, including the need to assess patients with PTSD for dissociative symptoms and to incorporate the treatment of dissociative symptoms into stage-oriented trauma treatment. PMID- 20360319 TI - International consensus study of antipsychotic dosing. AB - OBJECTIVE: Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated. METHOD: With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances. RESULTS: Participants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal function, illness stage and severity, sex, and diagnosis, were associated with dosing modifications. CONCLUSIONS: In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials. PMID- 20360320 TI - Performance-based measures of everyday function in mild cognitive impairment. AB - OBJECTIVE: The view that everyday function is preserved in mild cognitive impairment may be problematic. The objectives of this study were to determine the magnitude of impairment in everyday function in patients with mild cognitive impairment and Alzheimer's disease using a novel sensitive performance-based measure (the UCSD Performance-Based Skills Assessment; UPSA), contrast it with use of an informant-based measure (the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory; ADCS-ADL), and model the relationship between cognitive measures and the performance-based measure. METHOD: Fifty cognitively normal elders, 26 patients who met criteria for amnestic mild cognitive impairment, and 22 patients who suffered from mild to moderate Alzheimer's disease were assessed on the UPSA, the ADCS-ADL, and a battery of neurocognitive tests. RESULTS: Patients with mild cognitive impairment had significant impairments on the UPSA but not on the ADCS-ADL. The magnitude of the effect size between the cognitively healthy and the mild cognitive impairment group for the UPSA was large (d=0.86). A strong and significant relationship was observed between cognitive performances in speed (R(2)=0.37), episodic memory (R(2)=0.10), and semantic processing (R(2)=0.03) and UPSA score using multiple regression models. The psychometric properties of the UPSA were acceptable, as were its sensitivity and specificity in contrasts between cognitively normal elders and patients with mild cognitive impairment and between the latter group and patients with Alzheimer's disease. CONCLUSIONS: These findings indicate that performance-based measures of function may be a sensitive tool in studies of Alzheimer's disease and mild cognitive impairment and suggest the need for a reconceptualization of the relationship between cognition and function in mild cognitive impairment so that they can be usefully aligned. PMID- 20360321 TI - Does depression predict coronary heart disease and cerebrovascular disease equally well? The Health and Social Support Prospective Cohort Study. AB - BACKGROUND: The relationship between depression and cerebrovascular disease (CBVD) continues to be debated although little research has compared the predictive power of depression for coronary heart disease (CHD) with that for CBVD within the same population. This study aimed to compare the importance of depression for CHD and CBVD within the same population of adults free of apparent cardiovascular disease. METHODS: A random sample of 23,282 adults (9507 men, 13,775 women) aged 20-54 years were followed up for 7 years. Fatal and first non fatal CHD and CBVD events were documented by linkage to the National-hospital discharge and mortality registers. RESULTS: Sex-age-education-adjusted hazard ratio (HR) for CHD was 1.66 [95% confidence interval (CI) 1.24-2.24] for participants with mild to severe depressive symptoms, i.e. those scoring > or =10 on the 21-item Beck Depression Inventory, and 2.04 (1.27-3.27) for those who filled antidepressant prescriptions compared with those without depression markers in 1998, i.e. at study baseline. For CBVD, the corresponding HRs were 1.01 (0.67-1.53) and 1.77 (0.95-3.29). After adjustment for behavioural and biological risk factors these associations were reduced but remained evident for CHD, the adjusted HRs being 1.47 (1.08-1.99) and 1.72 (1.06-2.77). For CBVD, the corresponding multivariable adjusted HRs were 0.87 (0.57-1.32) and 1.52 (0.81 2.84). CONCLUSIONS: Self-reported depression using a standardized questionnaire and clinical markers of mild to severe depression were associated with an increased risk for CHD. There was no clear evidence that depression is a risk factor for CBVD, but this needs further confirmation. PMID- 20360322 TI - The shape of things to come in attention deficit hyperactivity disorder. PMID- 20360323 TI - "Splitting of the mind" revisited: recent neuroimaging evidence for functional dysconnection in schizophrenia and its relation to symptoms. PMID- 20360324 TI - Candidate gene studies in the GWAS era: the MET proto-oncogene, neurocognition, and schizophrenia. PMID- 20360325 TI - Neurocognition and white matter imaging: can the relationship be reliably quantified? PMID- 20360326 TI - The care and feeding of chairs of departments of psychiatry. PMID- 20360327 TI - Reflections on loss...of facial hair. PMID- 20360328 TI - Teaching trainees to negotiate research collaborations with industry: a mentorship model. AB - Research collaborations with the pharmaceutical industry can offer valuable opportunities for academic psychiatrists to gain access to important resources. Such relationships, however, often produce significant conflicts of interest, and recent attention has focused on the ways in which these conflicts can compromise research integrity. Psychiatric residents generally receive little education about industry-academia interactions. The authors report their experience collaborating on a research project with representatives of a pharmaceutical company, and they propose a model for teaching psychiatric trainees responsible and productive engagement with industry investigators. PMID- 20360329 TI - Jean Martin Charcot, 1825-1893: did he anticipate Freud's first topology? PMID- 20360330 TI - The effect of inmate populations on estimates of DSM-IV alcohol and drug use disorders in the United States. PMID- 20360331 TI - Suicide prevention on the Golden Gate Bridge. PMID- 20360332 TI - Dialectical behavior therapy versus general psychiatric management in the treatment of borderline personality disorder. PMID- 20360333 TI - Postpartum depression with psychotic features. PMID- 20360334 TI - Acute grief and physical pain. PMID- 20360335 TI - Neuroradiology of cholesteatomas. AB - The relevant aspects of cholesteatomas are reviewed with the emphasis on their diagnosis by using cross-sectional imaging. The indications and limitations of CT and MR imaging and the use of novel MR imaging techniques in the diagnosis of cholesteatomas are described. HRCT of the temporal bone has an excellent spatial resolution, thus even small soft-tissue lesions can be accurately delineated (high sensitivity). However, CT has poor specificity (ie, soft-tissue structures cannot be differentiated). MR imaging with the conventional sequences (T1WI, T2WI, postcontrast T1WI) provides additional information for distinguishing different pathologic entities and for accurately diagnosing primary (nonsurgical) and residual/recurrent (surgical) cholesteatomas. Higher diagnostic specificity is achieved by introducing DW-EPI, delayed postcontrast imaging, DW-non-EPI, and DWI-PROPELLER techniques. Studies using DW-non-EPI and DWI-PROPELLER sequences show promising results related to improved diagnostic sensitivity and specificity for even small (<5 mm) cholesteatomas, thus allowing avoidance of second-look surgery in the future. PMID- 20360336 TI - Role of CT angiographic plaque morphologic characteristics in addition to stenosis in predicting the symptomatic side in carotid artery disease. AB - BACKGROUND AND PURPOSE: Atherosclerotic disease of the carotid artery is an important cause of ischemic stroke. We evaluated carotid plaque morphologic features by using CTA in addition to stenosis in the setting of symptomatic hemispheric TIA/stroke to identify factors that may predict plaque activity. MATERIALS AND METHODS: Six hundred seventy-three patients (408 men; ages, 18-91 years; mean, 65.8 +/- 15.2 years) presenting with hemispheric ischemic symptoms and having a CTA that included imaging of both carotid arteries within 24 hours were studied. Scans were interpreted for morphologic features, such as plaque length and width, attenuation, shape, surface, presence and degree of calcification, and ILT in addition to stenosis. RESULTS: Univariable analysis showed that carotid occlusions (P = .01, OR = 5.27), high-grade stenosis (70% 99%) (P = .06, OR = 1.8), and the presence of ILT (P = .01, OR = 4.33) were highly predictive of the symptomatic side. Smooth plaque (P = .01, OR = 0.73) and extensive calcification (P = .03, OR = 0.72) were more commonly associated with the asymptomatic side. There was no correlation between plaque hypoattenuation (P = .7, OR = 1.06) or ulcerated plaque (P = .74, OR = 0.955) in predicting the symptomatic side. In a multivariable logistic regression model, the presence of ILT was still found to be significantly associated with the symptomatic side (P = .048, OR = 3.1) and the presence of extensive calcification, with the asymptomatic carotid artery (P = .047, OR = 0.69). CONCLUSIONS: In addition to higher stenosis grades, the presence of ILT is highly predictive of the symptomatic side in carotid disease. Smooth plaque and extensive calcification seem to afford a protective effect. This information may be useful in radiologic risk stratification in carotid disease in addition to the current evidence available based on stenosis criteria alone. PMID- 20360337 TI - Imaging characteristics of primary laryngeal lymphoma. AB - BACKGROUND AND PURPOSE: The larynx is a rare site for primary NHL. Fewer than 100 cases have been reported in the literature, with the largest imaging review involving only 4 patients. We describe the findings of laryngeal lymphoma on CT, PET, and MR imaging and identify features that may distinguish laryngeal lymphoma from the far more common laryngeal squamous cell carcinoma. MATERIALS AND METHODS: Multi-institutional retrospective chart review revealed 20 patients with histopathologically proved laryngeal lymphoma. Pretreatment CT, PET, and MR images were reviewed by a head and neck radiologist, focusing on extent of tumor, cervical lymph node involvement, and enhancement patterns. RESULTS: Patients ranged from 30 to 90 years of age with a mean of 63 years at the time of initial diagnosis and a 2:1 female predominance. The average tumor size was 37 +/- 19 mm. In all patients, laryngeal lymphoma involved the supraglottis but also extended into the glottis (65%) and hypopharynx (60%). The subglottis was less frequently involved (35%). Laryngeal cartilage invasion and cervical lymphadenopathy were each seen in 20% of patients. Lymphoma was consistently FDG-avid (100%) and usually enhanced uniformly with iodinated contrast (73%). Necrosis and calcification were not seen in any cases. CONCLUSIONS: Although laryngeal lymphoma is rare, particular imaging features suggest this diagnosis. A large uniformly enhancing supraglottic tumor without central necrosis and without cervical lymphadenopathy is a characteristic finding of lymphoma. Similar to squamous cell carcinoma, lymphoma may extend into the subglottis, pharynx, and laryngeal cartilages. PMID- 20360338 TI - Use of diffusion-weighted imaging to evaluate the initial response of progressive multifocal leukoencephalopathy to highly active antiretroviral therapy: early experience. AB - BACKGROUND AND PURPOSE: IRIS occurs in a small percentage of patients with AIDS following the initiation of HAART. Because PML lesions have a characteristic DWI/ADC appearance, our purpose was to determine if DWI/ADC measurements of PML lesions can be used to follow HAART treatment response and/or identify patients at risk for IRIS. MATERIALS AND METHODS: Six patients with AIDS and PML who had recently started HAART were retrospectively identified. On the basis of clinical history, patients were classified as having slow (non-IRIS) or rapid (IRIS) progression. Images were obtained at pre-HAART (time point 1) and post-HAART (time point 2). ADC parameters were measured and compared by using the 2-tailed t test. RESULTS: Seven lesions (4 rapidly progressing, 3 slowly progressing) were identified. Lesions from patients with rapid clinical progression had higher maximal ADC ratios at time point 1. There were also significant correlations between ADC parameters, time to clinical deterioration, and JCV titers. CONCLUSIONS: The ADC parameters of PML lesions were different for patients with rapid-versus-slow clinical progression. In our preliminary experience, ADC was helpful in diagnosing rapid clinical progression and IRIS. ADC values may correlate with the pathologic changes in PML lesions following HAART therapy. PMID- 20360339 TI - The present and the future of neuroimaging in amyotrophic lateral sclerosis. AB - In patients with ALS, conventional MR imaging is frequently noninformative, and its use has been restricted to excluding other conditions that can mimic ALS. Conversely, the extensive application of modern MR imaging-based techniques to the study of ALS has undoubtedly improved our understanding of disease pathophysiology and is likely to have a role in the identification of potential biomarkers of disease progression. This review summarizes how new MR imaging technology is changing dramatically our understanding of the factors associated with ALS evolution and highlights the reasons why it should be used more extensively in studies of disease progression, including clinical trials. PMID- 20360340 TI - T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age. AB - BACKGROUND AND PURPOSE: T2 relaxation times provide a continuous measure of changes in intervertebral disk biochemistry. The purpose of this study was to correlate T2 relaxation times in lumbar disks with patient age and stage of degeneration. MATERIALS AND METHODS: Sagittal T1- and T2-weighted images and axial images were acquired in 20 patients referred for MR imaging for back pain or radiculopathy. Two readers inspected these images and assigned a Pfirrmann grade to each disk. An additional sagittal multiecho FSE image sequence was obtained, and T2 relaxation times were calculated for a each lumbar disk. T2 relaxation times were correlated with Pfirrmann grade. T2 relaxation times in nondegenerated disks were correlated with patient age. Statistical significance was tested by ANOVA, ad hoc tests, and Pearson coefficients. RESULTS: T2 relaxation times were calculated for 95 lumbar disks in 19 patients and discarded for 5 disks in 1 patient due to motion artifacts. Forty-four disks were classified as Pfirrmann grade II; 34, as grade III; 14, as grade IV; and 3, as grade V. Mean T2 relaxation times of the central region decreased from 108 ms for grade II to 53 ms for grade IV disks. T2 relaxation times correlated significantly with Pfirrmann grade. For grade II disks, T2 relaxation times of the central region decreased significantly from an average of 132 ms for patients in their 20s to 86 ms for those in their 60s. CONCLUSIONS: T2 relaxation times in lumbar disks correlate with stage of degeneration and patient age. PMID- 20360341 TI - The triple rule-out for acute ischemic stroke: imaging the brain, carotid arteries, aorta, and heart. AB - BACKGROUND AND PURPOSE: Ischemic stroke is commonly embolic, either from carotid atherosclerosis or from cardiac origin. These potential sources of emboli need to be investigated to accurately prescribe secondary stroke prevention. Moreover, the mortality in ischemic stroke patients due to ischemic heart disease is greater than that of age-matched controls, thus making evaluation for coronary artery disease important in this patient population. The purpose of this study was to evaluate the image quality of a comprehensive CTA protocol in patients with acute stroke that expands the standard CTA coverage to include all 4 chambers of the heart and the coronary arteries. MATERIALS AND METHODS: One hundred twenty patients consecutively admitted to the emergency department with suspected cerebrovascular ischemia undergoing standard-of-care CTA were prospectively enrolled in our study. We used an original tailored acquisition protocol using a 64-section CT scanner, consisting of a dual-phase intravenous injection of iodinated contrast and saline flush, in conjunction with a dual phase CT acquisition, ascending from the top of the aortic arch to the vertex of the head, then descending from the top of the aortic arch to the diaphragm. No beta blockers were administered. The image quality, attenuation, and CNRs of the carotid, aortic, vertebral, and coronary arteries were assessed. RESULTS: Carotid, aorta, and vertebral artery image quality was 100% diagnostic (rated good or excellent) in all patients. Coronary artery image quality was diagnostic in 58% of RCA segments, 73% of LAD segments, and 63% of LCX segments. When we considered proximal segments only, the diagnostic quality rose to 71% in the RCA, 83% in the LAD, and 74% in the LCX. CONCLUSIONS: Our stroke protocol achieved excellent opacification of the left heart chambers, the cervical arteries, and each coronary artery, in addition to adequate carotid and coronary artery image quality. PMID- 20360342 TI - Intracranial stent placement for recanalization of acute cerebrovascular occlusion in 32 patients. AB - BACKGROUND AND PURPOSE: Stents have been reported as an option for improvement of the recanalization rate in AIS. The authors have also used intracranial stents in failed cases of IAT with pharmacologic and mechanical methods since 2004. We retrospectively reviewed our cases of intracranial stent use for IAT of AIS for recanalization and as a rescue procedure for iatrogenic intracranial vascular dissection during IAT. MATERIALS AND METHODS: Thirty-two patients, who were diagnosed with AIS, were treated with intracranial stents (28 balloon-mounted and 7 self-expandable stents) at our neurovascular center between April 2004 and December 2008. The stent use for all 32 patients was the final attempt to recanalize occluded vessels after various trials of pharmacologic or mechanical thrombolysis or to treat iatrogenic vascular dissection. RESULTS: Among the 32 patients, immediate poststenting angiographic recanalization was achieved in 100% with TIMI/TICI 2 (15 of 32 lesions, 46.9%) or TIMI/TICI 3 (17 of 32 lesions, 53.1%). However, complication rates were also high. Major symptomatic intracerebral hemorrhage (1 case of procedural symptomatic hemorrhage and 3 cases of delayed symptomatic hemorrhage) occurred in 4 (12.5%); intracranial vascular dissection, in 4 (12.5%); extracranial vascular dissection, in 3 (9.4%); immediate IST, in 4 (12.5%); subacute (within 1 week) IST, in 2; late (>1 week) IST, in 1, and 1 case of in-stent restenosis occurred twice (at 5 and 17 months). CONCLUSIONS: Intracranial stent placement for AIS management has an excellent recanalization rate. However, it is associated with high complication risks as our series showed. We believe that the decision to treat AIS with intracranial stent placement should be made after careful consideration of potential benefits and risks. PMID- 20360343 TI - Feasibility of angiographic CT in peri-interventional diagnostic imaging: a comparative study with multidetector CT. AB - BACKGROUND AND PURPOSE: The ability to perform neuroimaging on the angiography suite is important in making decisions during neurointerventions. Our aim was the evaluation of ACT as a fast available diagnostic tool during and after neuroendovascular procedures and the comparison of ACT with postinterventional MDCT. MATERIALS AND METHODS: Eighty-four peri-interventional ACT acquisitions were obtained and evaluated: 38 after coil embolization of cerebral aneurysms, 16 after intracranial angioplasty with stent placement, and 30 after endovascular mechanical thrombectomy and lysis. Interventions and ACTs were performed on a biplane angiography system equipped with flat panel detectors. Postprocessing was performed on a dedicated workstation, and multiplanar reformations were generated. Reference studies were performed on a 16- or 128-section MDCT scanner. All studies were independently evaluated by 3 blinded neuroradiologists. The Wilcoxon test was applied for the statistical analysis. RESULTS: ACT and MDCT images were of equal diagnostic quality in most cases related to the supratentorial ventricular system and the detection of hemorrhages (subarachnoidal, intraparenchymal, and intraventricular). Regarding the supratentorial ventricular system, an adequate diagnostic quality was assigned to 94% of the ACT acquisitions. For the detection of hemorrhage, no statistically significant difference was noted between ACT and MDCT. However, for the infratentorial region, ACT performed relatively poorly compared with MDCT. The diagnostic evaluation of gray matter (basal ganglia, insular cortex, and central cortex) by ACT is not sufficient, with <20% of the acquisitions scoring a diagnostic value. CONCLUSIONS: After neuroendovascular procedures and within the angiography suite, ACT enables an immediate detection of peri-interventional hemorrhage or hydrocephalus. However, for the detection of cerebral infarction, ACT is not yet reliable. PMID- 20360344 TI - Impact of superselective transarterial infusion therapy of high-dose cisplatin on maxillary cancer with orbital invasion. AB - BACKGROUND AND PURPOSE: We have been performing the superselective transarterial infusion of high-dose cisplatin for advanced maxillary cancer since 1998 and the local control rate, disease free survival rate, and organ preservation have improved markedly compared with our former therapy. This study evaluates the effectiveness of superselective transarterial infusion therapy by using high-dose cisplatin on maxillary cancer with orbital invasion. MATERIALS AND METHODS: We treated 23 patients with maxillary cancer by using superselective transarterial infusion therapy with high-dose cisplatin and concomitant radiation therapy for 10 years. Of all patients, 15 showed orbital invasion, with 11 of these tumors fed by both internal maxillary and ophthalmic arteries. In all patients, we performed superselective transarterial infusion therapy via the internal maxillary artery and/or the other feeding branches from the external carotid artery. After the operation, we determined whether a pCR had occurred by checking for the presence of viable cells. In addition, we calculated the overall survival rate, preservation rate of the eyeball, and disease-free survival rate. RESULTS: For all 23 patients, pCR and overall survival rates were 95.7% and 78.4%, respectively. To date, 2 of these patients died of lung metastasis without local recurrence. For the 15 patients with orbital invasion, the respective pCR and disease-free survival rates were 93.3% and 87.5%. Eyeballs were preserved in all patients, and local recurrence occurred in only 1 patient, at the inferior wall of the maxillary sinus (not in the orbit). CONCLUSIONS: Superselective transarterial infusion therapy with high-dose cisplatin remarkably improved the local control rate and disease-free survival rate of maxillary cancer. Even in patients with orbital invasion, a high local control rate was achieved, with preservation of the eyeball, through infusion only into branches of the external carotid artery. PMID- 20360346 TI - Report of spectroscopy findings not the first. PMID- 20360345 TI - Potent risk factor for aneurysm formation: termination aneurysms of the anterior communicating artery and detection of A1 vessel asymmetry by flow dilution. AB - BACKGROUND AND PURPOSE: There is a high incidence of intracranial aneurysms of the AcomA suggesting the possibility of an anatomic risk factor. There also exists an association of termination-type aneurysms with anatomic variations of 1 anterior cerebral artery trunk (A1) as the exclusive or dominant supply to both pericallosal arteries (A2). This yields the hypotheses of aneurysm formation from straight jets of A1 blood. MATERIALS AND METHODS: The anatomy and contrast filling of A1 and A2 segments and AcomAs were studied for a subset of cases entered into the Cerecyte Coil Trial for patients with AcomA (n = 105) and other aneurysms (n = 123) that were selected from imaging available at the Cerecyte Core Trial angiographic Core Lab. These cases were analyzed for A1 vessel dominance by measurement of the vessel diameter and dilution of angiographic contrast agent in A2s due to the differential flow source on selective angiography. A control group without aneurysms was assessed anatomically, using a large sequential CTA series (n = 159), acquired during acute stroke assessment. RESULTS: A1 dominance configuration is strongly associated with the presence of AcomA aneurysms for patients with intracranial aneurysms (odds ratio, 17.8). This association is also present compared with the incidence of A1 dominance in the large sequential control series of patients without aneurysms undergoing CTA for other reasons (odds ratio, 7.5). Outflow dilution of selective angiographic images augments anatomic information. CONCLUSIONS: A flow-based assessment of contrast flowing from the A1 to the A2 segments after injection pressure is superior to an A1 diameter based categorization when A1 vessel diameters are not strikingly different. The anatomic variant of asymmetric A1 configurations likely facilitates the development of AcomA aneurysms by flow stresses, providing further evidence to support the role of biophysical factors in intracranial aneurysm development. PMID- 20360347 TI - Listening to music. PMID- 20360348 TI - Syndromes of the first and second branchial arches, part 2: syndromes. AB - A variety of congenital syndromes affecting the face occur due to defects involving the first and second BAs. Radiographic evaluation of craniofacial deformities is necessary to define aberrant anatomy, plan surgical procedures, and evaluate the effects of craniofacial growth and surgical reconstructions. High-resolution CT has proved vital in determining the nature and extent of these syndromes. The radiologic evaluation of syndromes of the first and second BA should begin first by studying a series of isolated defects (cleft lip with or without CP, micrognathia, and EAC atresia) that compose the major features of these syndromes and allow a more specific diagnosis. After discussion of these defects and the associated embryology, we discuss PRS, HFM, ACS, TCS, Stickler syndrome, and VCFS. PMID- 20360349 TI - Association of venous malformation of the head and neck with meningoencephalocele: report of 3 cases. AB - Venous malformations have previously been reported to be associated with skeletal changes in humans, typically demineralization and localized deformation of the long bones. We report a presumed developmental association between venous malformations of the head and neck and meningoencephaloceles involving the sphenoid and temporal bones. Recognition of this association is important to avoid misinterpretation of these changes as a more aggressive process. We present the imaging findings and suggest an embryologic basis for this previously unreported association. PMID- 20360350 TI - Asymmetric frontal cortical activity and negative affective responses to ostracism. AB - Ostracism arouses negative affect. However, little is known about variables that influence the intensity of these negative affective responses. Two studies fill this void by incorporating work on approach- and withdrawal-related emotional states and their associated cortical activations. Study 1 found that following ostracism anger related directly to relative left frontal cortical activation. Study 2 used unilateral hand contractions to manipulate frontal cortical activity prior to an ostracizing event. Right-hand contractions, compared to left-hand contractions, caused greater relative left frontal cortical activation during the hand contractions as well as ostracism. Also, right-hand contractions caused more self-reported anger in response to being ostracized. Within-condition correlations revealed patterns of associations between ostracism-induced frontal asymmetry and emotive responses to ostracism consistent with Study 1. Taken together, these results suggest that asymmetrical frontal cortical activity is related to angry responses to ostracism, with greater relative left frontal cortical activity being associated with increased anger. PMID- 20360351 TI - Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR. AB - A functional variant of the serotonin transporter gene (5-HTTLPR) has been associated with increased risk for major depression in the context of stress. In attempting to understand the mechanisms underlying this relation, we tested the hypothesis that 5-HTTLPR genotype affects the speed with which amygdala is recruited during emotional processing in young girls with no history of psychiatric disorder. We used functional magnetic resonance imaging to compare the rise time to peak amygdala activation in 5-HTTLPR short-allele carriers and long-allele homozygotes during enhancement of sad mood. Relative to long-allele homozygotes, participants with at least one copy of the 5-HTTLPR short allele showed both stronger and earlier activation in left amygdala as they increased a sad mood state. Individuals carrying the short allele appear to exhibit a neural 'readiness' to engage and enhance negative affect. Future research should examine how exposure to negative life events and more chronic sadness modify the time course of amygdala activity during the experience of negative emotion. PMID- 20360353 TI - Electrophysiologic and antiarrhythmic effects of AZD1305 in canine pulmonary vein sleeves. AB - The objective of this study was to examine the electrophysiologic and antiarrhythmic effects of the new antiarrhythmic agent tert-butyl (2-[7-[2-(4 cyano-2-fluorophenoxy)ethyl]-9-oxa-3,7-diazabicyclo[3.3.1]non3-yl]ethyl)carbamate (AZD1305) in canine pulmonary vein (PV) sleeve preparations isolated from untreated and long-term amiodarone-treated animals. Ectopic activity arising from PV sleeves plays a prominent role in the development of atrial fibrillation (AF). Delayed afterdepolarizations (DADs) and late phase 3 early afterdepolarizations (EADs), originating from the PV have been proposed as potential triggers in initiation of AF. Action potentials were recorded from canine superfused PV sleeves using standard microelectrode techniques. Acetylcholine (1 microM), isoproterenol (1 microM), or their combination was used to induce EADs, DADs, and triggered activity (TA). The effects of AZD1305 (0.1-10 microM) were evaluated in PV sleeve preparations isolated from untreated and amiodarone-treated (40 mg/kg daily for 6 weeks) dogs. AZD1305 (0.1-10 microM, 30 min) significantly prolonged action potential duration and reduced excitability. Abbreviating basic cycle length from 1000 to 300 ms resulted in a decrease of V(max) from 314 +/- 79 to 251 +/- 55 V/s (Delta = -20%) in control and from 177 +/- 53 to 76.5 +/- 33 V/s (Delta = -57%) after AZD1305 (n = 6, p < 0.05). AZD1305 markedly attenuated or suppressed DADs and DAD-induced TA, but not late phase 3 EADs. AZD1305-induced attenuation of excitability, leading to activation failure at much longer cycle lengths, was much more pronounced in PV from amiodarone-treated dogs. Potent effects of AZD1305 to depress excitability, prolong action potential duration, and suppress DAD-induced triggered activity in canine PV sleeve preparations may be effective in suppressing triggers responsible for the genesis of AF and other atrial arrhythmias. PMID- 20360354 TI - Purification of Tetrahymena nuclei by sedimentation at unit gravity. AB - This protocol provides a method for purification of Tetrahymena nuclei using sedimentation at unit gravity. It is useful for applications where purity of micro- and macronuclei is required beyond that which is typically achieved by differential sedimentation alone. When differential sedimentation is followed by sedimentation at unit gravity, micro- and macronuclei can be purified to virtual homogeneity. This method also permits the purification of homogeneous populations of developing new macronuclei (anlagen) and distinct classes of micronuclei from various stages of conjugation. PMID- 20360352 TI - Psychosocial biomarker research: integrating social, emotional and economic factors into population studies of aging and health. AB - There are complex reciprocal relationships between health and social, emotional and economic factors in aging populations. Social and affective neurosciences are rapidly developing an understanding of the mechanisms underlying these phenomena using sophisticated behavioural, neuroimaging and psychophysiological methods. These techniques are often complex and expensive, so are generally used in relatively small selected samples rather than in large-scale cohort studies. However, an understanding of the significance of these processes in health and well-being depends on integrating findings from social and affective neuroscience into population-level studies. The aim of this article is to describe how a population perspective on the determinants of health and well-being in old age articulates with the agenda of social, affective and economic neuroscience, particularly through the application of psychosocial biomarker research. Social and affective neuroscience and epidemiological approaches provide complementary research strategies for understanding the mechanisms linking social, emotional and economic factors with health risk. This will be illustrated primarily from findings from two studies conducted at University College London, the Whitehall II Study and the English Longitudinal Study of Ageing. PMID- 20360355 TI - Phenotypic analysis of Arabidopsis mutants: germination rate under salt/hormone induced stress. AB - Abiotic stress, such as high salt or low temperature, adversely affects plant growth and development. Salt stress inhibits seed germination, retards plant growth, and accelerates senescence. Freezing or drought stress can cause cell damage and plant death. The following parameters can be used to evaluate plant tolerance to salt, drought, or freezing stress: root elongation, fresh weight gain, seed germination (described here), electrolyte leakage, or water loss measurement. Several stress mutants have been characterized using these tests, including hos1 and hos2, which show higher expression of some stress-regulated genes when exposed to low-temperature stress; hos5, which shows higher expression of some stress-regulated genes under abscisic acid (ABA) and salt treatments; sfr mutants, which are deficient in freezing tolerance; and eskimo1, which is constitutively freezing-tolerant. This protocol describes a germination assay that can be carried out on seeds subjected to osmotic or hormone-induced stress. The seeds are plated on filter paper saturated with ABA (for hormonal stress) or with NaCl or mannitol (for osmotic stress). The germination rate can be scored on different days; germination is considered to have occurred when the radicles have penetrated the seed coats. The levels of stress suggested in this protocol may need to be adjusted, depending on the ecotype and growth conditions used. PMID- 20360356 TI - Isolation of Drosophila egg chambers for imaging. AB - The fruit fly Drosophila melanogaster is an important model for basic research into the molecular mechanisms underlying cell function and development, as well as a major biomedical research tool. A significant advantage of Drosophila is the ability to apply live cell imaging to a variety of living tissues that can be dissected and imaged in vivo, ex vivo, or in vitro. Drosophila egg chambers, for example, have proven to be a useful model system for studying border cell migration, Golgi unit transport, the rapid movement of mRNA and protein particles, and the role of microtubules in meiosis and oocyte differentiation. A crucial first step before imaging is preparation of the experimental material to ensure physiological relevance and to achieve the best conditions for image quality. Early- to mid-stage egg chambers cannot be mounted in an aqueous-based medium, because this causes a change in microtubule organization and follicle cell morphology. Such egg chambers survive better in Halocarbon oil, which allows free diffusion of oxygen, has low viscosity, and thus prevents dehydration and hypoxia. With a refractive index similar to glycerol, Halocarbon oil also has good optical properties for imaging. It also provides a good environment for injection and is particularly useful for long-term imaging of embryos. However, unlike with aqueous solutions, changes in the medium are not possible. This protocol describes the isolation of Drosophila egg chambers. PMID- 20360357 TI - Collection and mounting of Drosophila embryos for imaging. AB - The fruit fly Drosophila melanogaster is an important model for basic research into the molecular mechanisms underlying cell function and development, as well as a major biomedical research tool. A significant advantage of Drosophila is the ability to apply live cell imaging to a variety of living tissues that can be dissected and imaged in vivo, ex vivo, or in vitro. For example, such imaging can be used for visual genetic screens such as analysis of morphological characteristics or of the distribution of fluorescently tagged proteins in living embryos. Indeed, Drosophila embryos have proven to be a useful model system for studying a variety of cellular processes such as asymmetric division, migration, wound healing, apoptosis, and fasciculation, as well as for tracking lipid droplet motility, protein recycling, fast mRNA transport, and the movement of chromosomal loci within individual cells. A crucial first step before imaging is preparation of the experimental material to ensure physiological relevance and to achieve the best conditions for image quality. Because it contributes to autofluorescence and lack of transparency, it is useful to remove the chorion before imaging by treating the embryos with bleach. This protocol describes the collection and mounting of Drosophila embryos for live cell imaging. PMID- 20360358 TI - Drosophila macrophage preparation and screening. AB - Drosophila plasmatocytes, also known as macrophages, are part of the Drosophila innate immune system and also have roles during development. In late-stage embryos, it is possible to image macrophage migration in situ during development and when they converge at sites of wounding. This protocol describes the isolation of macrophages from third instar Drosophila larvae. The macrophages can be cultured for several hours, and fluorescently labeled macrophages can be screened using a fluorescence-imaging system. PMID- 20360359 TI - Drosophila larval fillet preparation and imaging of neurons. AB - Drosophila is an established system in which to study synaptic development, function, and plasticity. A particular advantage of the larval neuromuscular system is its consistent well-defined segmental arrangement of neurons and muscle targets. Indeed, the motor neurons of the Drosophila central nervous system are particularly well characterized in terms of origin, identity, morphology, and electrophysiology, and have been used for studies on axonal transport of organelles, vesicle trafficking, and recycling. To facilitate the identification of nerves and synapses in vivo, specific fluorescent protein markers can be used. For example, UASmCD8-green fluorescent protein (GFP) and UASmyr-red fluorescent protein (RFP) both preferentially label plasma membranes, whereas Discs large (DLG) reveals synapses. Gal4 drivers can be used to target all neurons (e.g., elavGal4) or specifically label motor neurons (e.g., d42Gal4). This protocol describes the dissection of Drosophila larvae to isolate neurons for live cell imaging. PMID- 20360360 TI - Introduction of green fluorescent protein (GFP) into hippocampal neurons through viral infection. AB - Expression of green fluorescent protein (GFP), its more fluorescent mutant forms (e.g., EGFP [enhanced GFP]), or their fusion protein derivatives, affords a number of informative possibilities in cellular neuroscience. EGFP is a soluble protein and appears to be homogeneously distributed within the cytosol of neurons when expressed. Thus, it reveals the structure of the neuron, including the cell body, and axonal and dendritic arbors. It is also sufficiently bright to reveal detailed structures such as axonal boutons and dendritic spines. When expressed as a fusion protein, EGFP can provide information about the distribution characteristics of the proteins within neurons. Furthermore, during single-cell electrophysiological studies, such expression can direct the investigator to record from a cell carrying a foreign gene. In this protocol, we describe the use of the Sindbis pseudovirus expression system to deliver GFP to neurons. Sindbis is a member of the alphaviruses, which are plus-stranded RNA viruses. This protocol uses the DH(26S) strain, which preferentially infects neurons over glia (50:1). Two infection methods are given: one for dissociated hippocampal cultured neurons and one for organotypic hippocampal slices. PMID- 20360361 TI - Preparation of Trojan horse liposomes (THLs) for gene transfer across the blood brain barrier. AB - Nonviral plasmid DNA is delivered to the brain via a transvascular route across the blood-brain barrier (BBB) following intravenous administration of DNA encapsulated within Trojan horse liposomes (THLs), also called PEGylated immunoliposomes (PILs). The liposome surface is covered with several thousand strands of polymer (e.g., polyethylene glycol [PEG]), and the tips of 1%-2% of the polymer strands are conjugated with a targeting monoclonal antibody that acts as a molecular Trojan horse (MTH). The MTH binds to a receptor (e.g., for transferrin or insulin) on the BBB and brain cell membrane, triggering receptor mediated transcytosis of the THL across the BBB in vivo, and receptor-mediated endocytosis into brain cells beyond the BBB. The persistence of transgene expression in the brain is inversely related to the rate of degradation of the episomal plasmid DNA. THL technology enables an exogenous gene to be widely expressed in the majority of cells in adult brain (or other organs) within 1 d of a single intravenous administration. Applications of the THLs include tissue specific gene expression with tissue-specific promoters, complete normalization of striatal tyrosine hydroxylase in experimental Parkinson's disease following intravenous tyrosine hydroxylase gene therapy, a 100% increase in survival time of mice with brain tumors following weekly intravenous antisense gene therapy using THLs, and a 90% increase in survival time with weekly intravenous RNA interference (RNAi) gene therapy in mice with intracranial brain tumors. This protocol describes the preparation of THLs for use in gene transfer in vitro or in vivo. PMID- 20360362 TI - Optimized DNA preparation from mycobacteria. AB - Extraction of genomic DNA from mycobacteria requires special consideration because (i) many mycobacterial species exhibit extremely slow growth, and thus produce only small amounts of starting material, and (ii) a robust and waxy cell wall renders mycobacteria difficult to lyse. Hence, mycobacterial DNA extraction often results in low DNA yields of unsuitable quality. Published protocols for mycobacterial DNA preparations and commercially available extraction kits are mainly designed for the isolation of small amounts of genomic material suitable for polymerase chain reaction (PCR)-based applications like species identification. However, such DNA quantities and qualities are usually not sufficient for contemporary genomic analyses such as whole genome sequence analysis, single nucleotide polymorphism (SNP) detection, or DNA microarrays, or for investigations of bacterial evolution, virulence, or epidemiology on a world wide population level. Moreover, most protocols that achieve a high standard in DNA recovery typically employ large reaction volumes and thus require milliliter scale plasticware and centrifugal equipment as well as large amounts of chemicals, all of which are costly both in purchase and disposal. The DNA extraction method described here was established to address the challenges that result from the slow growth and distinct cell wall composition of mycobacteria, and to greatly enhance both yield and purity of mycobacterial DNA preparations in a small extraction volume. Designed to be performed using 1.5-mL reaction tubes and the corresponding equipment, the method is economical and practical, and reliably yields large amounts of pure genomic DNA--increases of at least 10-fold as compared to earlier protocols. PMID- 20360363 TI - Identifying and removing artificial replicates from 454 pyrosequencing data. AB - An intrinsic artifact of 454-based pyrosequencing leads to artificial overrepresentation of >10% of the original DNA sequencing templates. This artificial amplification of sequences is unbiased with regard to position on the pyrosequencing plate or sequence identity, and it occurs in all currently available 454 technologies. The amplified sequences start at the same position and are identical (duplicates), or vary in length, or contain a sequencing discrepancy. If the abundance of any sequence in a data set is going to be enumerated, either for comparative community analysis, transcriptional analysis or other applications, it is important to remove these artificial replicates before analysis. A web-based tool that incorporates the clustering algorithm cd hit was developed to identify and remove artificially replicated sequences in 454 based pyrosequencing data sets. This tool cannot be used for data sets that have an initial amplification step before the standard pyrosequencing procedure, because artificial replicates cannot be distinguished from expected replication due to polymerase chain reaction (PCR) amplification, e.g., in sequencing of amplified gene "tags." This protocol provides details on how to use the replicate filter and obtain a file of unique sequences for use in metagenomic or transcriptomic analyses. PMID- 20360364 TI - Calcium imaging of neuronal circuits in vivo using a circuit-tracing pseudorabies virus. AB - Pseudorabies virus (PRV) is a neuroinvasive virus of the herpes family that has a broad host range but does not infect higher-order primates. PRV characteristically travels along chains of synaptically connected neurons and has been used extensively for elucidating neural circuits in the peripheral and central nervous system in vivo. The recombinant virus PRV369 is an attenuated retrograde tracer that encodes G-CaMP2, a fluorescent calcium sensor protein that is stable at physiological pH and mammalian temperature. This protocol describes the use of PRV369 to express G-CaMP2 in a neuronal circuit and to monitor its activity in a living animal, specifically in the submandibular ganglia (SMG), the peripheral parasympathetic ganglia that innervate the salivary glands. The procedure describes the delivery of PRV369 to the glands and shows how SMG neurons can then be imaged post-inoculation to explore connectivity and activity. PMID- 20360365 TI - Pouring linear gradient gels with a gradient former. AB - Linear gradient gels, which are polyacrylamide gels having a gradient of increasing acrylamide concentration (and linearly decreasing pore size), can have advantages over fixed-concentration SDS-PAGE gels. First, a much greater range of protein M(r) values can be separated on a linear gradient gel than on a fixed concentration gel. Second, there is a greater likelihood of resolving proteins with very similar M(r) values on gradient gels than on fixed-concentration gels. This protocol describes the pouring of linear gradient gels with a gradient former. The most common gradient gel contains 4%-20% acrylamide; however, the range of acrylamide concentrations should be chosen on the basis of the size of the proteins being separated. PMID- 20360366 TI - CTAB-PAGE. AB - Although SDS-PAGE is the method of choice for most denaturing gel electrophoresis procedures, the anionic detergent SDS still presents some drawbacks. For example, SDS forms crystals at low temperatures and, in some cases, causes proteins to aggregate or precipitate. In addition, some proteins are not well-resolved in SDS gels or may migrate anomalously. In these situations, the use of a cationic detergent for PAGE offers an alternative approach. The system described in this protocol uses the cationic detergent cetyltrimethyl ammonium bromide (CTAB) and includes a stacking gel based on the zwitterion arginine (used as a stacking agent) and tricine (N-tris[hydroxymethyl]-methylglycine) used as a counterion and buffer. Some proteins separated on the CTAB electrophoresis system retain their native enzymatic activity, provided the samples are prepared without boiling and without the addition of a reducing agent. PMID- 20360367 TI - Rapid coomassie blue staining of protein gels. AB - Coomassie brilliant blue R250 (CBR-250) and silver staining are the most widely used methods for the routine visualization of proteins separated by SDS-PAGE. CBR 250 is an organic dye that complexes with basic amino acids, such as arginine, lysine, and histidine, as well as tyrosine. Conventional CBR-250 staining is capable of detecting as little as 30-100 ng of protein, but sensitivity can be improved by performing the staining and destaining at elevated temperatures. The method described in this protocol, which is a modified version of the conventional Coomassie protocol, speeds up the destaining process for faster results with increased sensitivity and is compatible with mass-spectrometry-based methods for identifying proteins. PMID- 20360368 TI - SYPRO Orange fluorescent staining of protein gels. AB - This method for staining protein gels uses a fluorescent dye, SYPRO Orange, which is very sensitive to protein (4-10 ng protein/band). SYPRO Orange cannot be visualized with the naked eye and thus a fluorescence scanner is required for detection of protein bands (the excitation maxima [Ex] are 300/472 nm and the emission maximum [Em] is 570 nm). SYPRO Red fluorescent protein stain uses the same binding principle as SYPRO Orange; hence, this protocol can also be used for SYPRO Red stain (Ex are 300/550 nm and Em is 630 nm). This staining method is mass-spectrometer-compatible. PMID- 20360369 TI - Multiply primed rolling-circle amplification method for the amplification of circular DNA viruses. AB - The use of whole genome amplification and analysis of viruses is of increasing importance, as data generated using these methods are currently used for clinical diagnostics, epidemiological studies, phylogenetic analyses, and studies of genome organization and evolution. The best known amplification method for DNA is the polymerase chain reaction (PCR). This technique, however, has drawbacks: PCR produces relatively small amplicons and also requires prior knowledge of sequence data for the construction of the required consensus or degenerate primers. For circular DNA templates, it is possible to overcome these drawbacks by using the multiply primed rolling-circle amplification (RCA) technique, which mimics the rolling-circle mechanism that occurs in nature for replication of circular DNA molecules, e.g., plasmids. The RCA protocol described here is optimized for the amplification of circular DNA virus genomes. PMID- 20360370 TI - The mouse cornea as a transplantation site for live imaging of engineered tissue constructs. AB - The field of tissue engineering aims to recapitulate healthy human organs and 3-D tissue structures in vitro and then transplant these constructs in vivo where they can be effectively integrated within the recipient patient and become perfused by the host circulation. To improve the design of materials for artificial tissue scaffolds, it would be ideal to have a high-throughput imaging system that allows one to directly monitor transplanted tissue constructs in live animals over an extended period of time. By combining such an assay with transgenic, cell-specific fluorescent reporters, one could monitor such parameters as tissue construct perfusion, donor cell survival, and donor-host cell interaction/integration. Here, we describe a protocol for a modified version of the classical corneal micropocket angiogenesis assay, employing it as a live imaging "window" to monitor angiogenic poly(ethylene glycol) (PEG)-based hydrogel tissue constructs. PMID- 20360371 TI - rAAV9--a human-derived adeno-associated virus vector for efficient transgene expression in mouse cingulate cortex. AB - The rostro-medial cortex of the mouse and rat, considered the functional homolog to the primate prefrontal cortex (PFC), is of growing importance for preclinical models of schizophrenia and other neurodevelopmental diseases for which symptoms typically emerge in adolescence and early adulthood. Therefore, in order to explore molecular mechanisms operating during these critical stages of PFC development, it will be important to develop an efficient gene delivery system for the PFC of juvenile animals. To this end, adeno-associated virus (AAV)-based systems are increasingly used in mice for targeted gene delivery in specific brain regions such as the hippocampus. Strikingly, there is very little literature on vector-mediated gene expression in the rostro-medial cortex. In addition, multiple AAV serotypes exist based on differences in their envelope capsid proteins. However, to date, the large majority of studies in the central nervous system (CNS) have utilized the AAV2 serotype. This is typically limited to a very focal transduction pattern and therefore is not ideal for the murine PFC, which occupies several square millimeters in the rostral hemisphere. Here, we introduce a protocol for efficient, AAV9-serotype-mediated gene delivery in juvenile (postnatal day 21) and young adult PFC, resulting in long-lasting transgene expression. PMID- 20360379 TI - Live cell imaging in Drosophila melanogaster. AB - Although many of the techniques of live cell imaging in Drosophila melanogaster are also used by the greater community of cell biologists working on other model systems, studying living fly tissues presents unique difficulties with regard to keeping the cells alive, introducing fluorescent probes, and imaging through thick, hazy cytoplasm. This article outlines the major tissue types amenable to study by time-lapse cinematography and different methods for keeping the cells alive. It describes various imaging and associated techniques best suited to following changes in the distribution of fluorescently labeled molecules in real time in these tissues. Imaging, in general, is a rapidly developing discipline, and recent advances in imaging technology are able to greatly extend what can be achieved with live cell imaging of Drosophila tissues. As far as possible, this article includes the latest technical developments and discusses likely future developments in imaging methods that could have an impact on research using Drosophila. PMID- 20360380 TI - Green fluorescent proteins (GFPs) for measuring voltage. AB - Measuring signal transduction in large numbers of cells, with high spatial and temporal resolution, is a fundamental problem for studying information processing in the nervous system. To address this problem, a family of detectors that are chimeras between signal transduction proteins and fluorescent proteins has been designed. The prototype sensor is a genetically encoded probe that can be used to measure transmembrane voltage in single cells. This article describes a modified green fluorescent protein (GFP), fused to a voltage-sensitive K(+) channel, so that voltage-dependent rearrangements in the K(+) channel induce changes in the fluorescence of GFP. The probe has a maximal fractional fluorescence change of 5.1%, making it comparable to some of the best organic voltage-sensitive dyes. Moreover, the fluorescent signal is expanded in time in a manner that makes the signal 30-fold easier to detect than a traditional linear dye. DNA-encoded sensors have the advantage that they may be introduced into an organism noninvasively and targeted to specific brain regions, cell types, and subcellular compartments. PMID- 20360381 TI - Understanding neuronal connectivity through the post-transcriptional toolkit. AB - Post-transcriptional regulatory mechanisms have emerged as a critical component underlying the diversification and spatiotemporal control of the proteome during the establishment of precise neuronal connectivity. These mechanisms have been shown to be important for virtually all stages of assembling a neural network, from neurite guidance, branching, and growth to synapse morphogenesis and function. From the moment a gene is transcribed, it undergoes a series of post transcriptional regulatory modifications in the nucleus and cytoplasm until its final deployment as a functional protein. Initially, a message is subjected to extensive structural regulation through alternative splicing, which is capable of greatly expanding the protein repertoire by generating, in some cases, thousands of functionally distinct isoforms from a single gene locus. Then, RNA packaging into neuronal transport granules and recognition by RNA-binding proteins and/or microRNAs is capable of restricting protein synthesis to selective locations and under specific input conditions. This ability of the post-transcriptional apparatus to expand the informational content of a cell and control the deployment of proteins in both spatial and temporal dimensions is a feature well adapted for the extreme morphological properties of neural cells. In this review, we describe recent advances in understanding how post-transcriptional regulatory mechanisms refine the proteomic complexity required for the assembly of intricate and specific neural networks. PMID- 20360382 TI - How does the royal family of Tudor rule the PIWI-interacting RNA pathway? AB - PIWI (P-element-induced wimpy testis) proteins are a subset of the Argonaute proteins and are expressed predominantly in the germlines of a variety of organisms, including Drosophila and mammals. PIWI proteins associate specifically with PIWI-interacting RNAs (piRNAs), small RNAs that are also expressed predominantly in germlines, and silence transposable DNA elements and other genes showing complementarities to the sequences of associated piRNAs. This mechanism helps to maintain the integrity of the genome and the development of gametes. PIWI proteins have been shown recently to contain symmetrical dimethyl arginines (sDMAs), and this modification is mediated by the methyltransferase PRMT5 (also known as Dart5 or Capsuleen). It was then demonstrated that multiple members of the Tudor (Tud) family of proteins, which are necessary for gametogenesis in both flies and mice, associate with PIWI proteins specifically through sDMAs in various but particular combinations. Although Tud domains in Tud family members are known to be sDMA-binding modules, involvement of the Tudor family at the molecular level in the piRNA pathway has only recently come into focus. PMID- 20360383 TI - Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells. AB - The stability of a lineage program (cellular memory) is dependent on mechanisms that epigenetically maintain active or repressed states of gene expression (transcriptional memory). Although epigenetic silencing of genes has been clearly demonstrated from yeast to mammals, heritable maintenance of active transcription has been less clearly defined. To investigate the potential role of active transcriptional memory during lineage diversification, we employed targeted mutation of a positive-acting cis element in the Cd4 locus to determine the impact on CD4 expression and the differentiation of CD4(+) helper T cells in mice. We show that the proximal enhancer (E4(P)) of Cd4 is essential for CD4 expression in immature CD4(+)8(+) thymocytes. Furthermore, its loss resulted in reduced and unstable expression of CD4 in mature T cells. However, if the enhancer was deleted after cells had already committed to the helper T-cell lineage, CD4 expression remained high and was stable upon cell division. "Active" histone modifications, once initiated by E4(P), were also propagated independently of the enhancer. Thus, E4(P) is responsible for establishing an epigenetically inherited active Cd4 locus in the helper T-cell lineage. To our knowledge, this is the first genetic demonstration of active transcriptional memory in mammalian cells. PMID- 20360384 TI - The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. AB - The transcriptional program orchestrated by Hedgehog signaling depends on the Gli family of transcription factors. Gli proteins can be converted to either transcriptional activators or truncated transcriptional repressors. We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the formation of either repressor or activator forms of Gli3. In the absence of signaling, Sufu restrains Gli3 in the cytoplasm, promoting its processing into a repressor. Initiation of signaling triggers the dissociation of Sufu from Gli3. This event prevents formation of the repressor and instead allows Gli3 to enter the nucleus, where it is converted into a labile, differentially phosphorylated transcriptional activator. This key dissociation event depends on Kif3a, a kinesin motor required for the function of primary cilia. We propose that the Sufu-Gli3 interaction is a major control point in the Hedgehog pathway, a pathway that plays important roles in both development and cancer. PMID- 20360385 TI - The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. AB - Malignant gliomas are the most common primary brain tumors, and are associated with frequent resistance to therapy as well as poor prognosis. Here we demonstrate that the nuclear receptor tailless (Tlx), which in the adult is expressed exclusively in astrocyte-like B cells of the subventricular zone, acts as a key regulator of neural stem cell (NSC) expansion and brain tumor initiation from NSCs. Overexpression of Tlx antagonizes age-dependent exhaustion of NSCs in mice and leads to migration of stem/progenitor cells from their natural niche. The increase of NSCs persists with age, and leads to efficient production of newborn neurons in aged brain tissues. These cells initiate the development of glioma-like lesions and gliomas. Glioma development is accelerated upon loss of the tumor suppressor p53. Tlx-induced NSC expansion and gliomagenesis are associated with increased angiogenesis, which allows for the migration and maintenance of brain tumor stem cells in the perivascular niche. We also demonstrate that Tlx transcripts are overexpressed in human primary glioblastomas in which Tlx expression is restricted to a subpopulation of nestin-positive perivascular tumor cells. Our study clearly demonstrates how NSCs contribute to brain tumorgenesis driven by a stem cell-specific transcription factor, thus providing novel insights into the histogenesis and molecular pathogenesis of primary brain tumors. PMID- 20360386 TI - The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. AB - The homeobox gene Prox1 is crucial for mammalian lymphatic vascular development. In the absence of Prox1, lymphatic endothelial cells (LECs) are not specified. The maintenance of LEC identity also requires the constant expression of Prox1. However, the mechanisms controlling the expression of this gene in LECs remain poorly understood. The SRY-related gene Sox18 is required to induce Prox1 expression in venous LEC progenitors. Although Sox18 is also expressed in embryonic arteries, these vessels do not express Prox1, nor do they give rise to LECs. This finding suggests that some venous endothelial cell-specific factor is required for the activation of Prox1. Here we demonstrate that the nuclear hormone receptor Coup-TFII is necessary for the activation of Prox1 in embryonic veins by directly binding a conserved DNA domain in the regulatory region of Prox1. In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of Prox1 expression during early stages of LEC specification and differentiation. PMID- 20360387 TI - CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP. AB - The estrogen receptor alpha (ERalpha) is activated as a transcription factor by both estrogen and a large variety of other extracellular signals. The mechanisms of this ligand-independent activation, notably by cAMP signaling, are still largely unknown. We now close the gap in the signaling pathway between cAMP and ERalpha. Whereas the direct phosphorylation of ERalpha by the cAMP-activated protein kinase A (PKA) is dispensable, the phosphorylation of the coactivator associated arginine methyltransferase 1 (CARM1) by PKA at a single serine is necessary and sufficient for direct binding to the unliganded hormone-binding domain (HBD) of ERalpha, and the interaction is necessary for cAMP activation of ERalpha. Sustained PKA activity promoting a constitutive interaction may contribute to tamoxifen resistance of breast tumors. Binding and activation involve a novel regulatory groove of the ERalpha HBD. As a result, depending on the activating signal, ERalpha recruits different coactivator complexes to regulate alternate sets of target genes. PMID- 20360388 TI - Dicentric breakage at telomere fusions. AB - Nonhomologous end-joining (NHEJ) inhibition at telomeres ensures that native chromosome ends do not fuse together. But the occurrence and consequences of rare telomere fusions are not well understood. It is notably unclear whether a telomere fusion could be processed to restore telomere ends. Here we address the behavior of individual dicentrics formed by telomere fusion in the yeast Saccharomyces cerevisiae. Our approach was to first stabilize and amplify fusions between two chromosomes by temporarily inactivating one centromere. Next we analyzed dicentric breakage following centromere reactivation. Unexpectedly, dicentrics often break at the telomere fusions during progression through mitosis, a process that restores the parental chromosomes. This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres. PMID- 20360389 TI - mRNA deep sequencing reveals 75 new genes and a complex transcriptional landscape in Mimivirus. AB - Mimivirus, a virus infecting Acanthamoeba, is the prototype of the Mimiviridae, the latest addition to the nucleocytoplasmic large DNA viruses. The Mimivirus genome encodes close to 1000 proteins, many of them never before encountered in a virus, such as four amino-acyl tRNA synthetases. To explore the physiology of this exceptional virus and identify the genes involved in the building of its characteristic intracytoplasmic "virion factory," we coupled electron microscopy observations with the massively parallel pyrosequencing of the polyadenylated RNA fractions of Acanthamoeba castellanii cells at various time post-infection. We generated 633,346 reads, of which 322,904 correspond to Mimivirus transcripts. This first application of deep mRNA sequencing (454 Life Sciences [Roche] FLX) to a large DNA virus allowed the precise delineation of the 5' and 3' extremities of Mimivirus mRNAs and revealed 75 new transcripts including several noncoding RNAs. Mimivirus genes are expressed across a wide dynamic range, in a finely regulated manner broadly described by three main temporal classes: early, intermediate, and late. This RNA-seq study confirmed the AAAATTGA sequence as an early promoter element, as well as the presence of palindromes at most of the polyadenylation sites. It also revealed a new promoter element correlating with late gene expression, which is also prominent in Sputnik, the recently described Mimivirus "virophage." These results-validated genome-wide by the hybridization of total RNA extracted from infected Acanthamoeba cells on a tiling array (Agilent)--will constitute the foundation on which to build subsequent functional studies of the Mimivirus/Acanthamoeba system. PMID- 20360390 TI - ARBITER 6-HALTS. Does it have the power to settle all matters? PMID- 20360391 TI - Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate. AB - With over 200 million people infected with hepatitis C virus (HCV) worldwide, there is a need for more effective and better-tolerated therapeutic strategies. The HCV genome is a positive-sense; single-stranded RNA encoding a large polyprotein cleaved at multiple sites to produce at least ten proteins, among them an error-prone RNA polymerase that confers a high mutation rate. Despite considerable overall sequence diversity, in the 3'-untranslated region of the HCV genomic RNA there is a 98-nucleotide (nt) sequence named X RNA, the first 55 nt of which (X55 RNA) are 100% conserved among all HCV strains. The X55 region has been suggested to be responsible for in vitro dimerization of the genomic RNA in the presence of the viral core protein, although the mechanism by which this occurs is unknown. In this study, we analyzed the X55 region and characterized the mechanism by which it mediates HCV genomic RNA dimerization. Similar to a mechanism proposed previously for the human immunodeficiency 1 virus (HIV-1) genome, we show that dimerization of the HCV genome involves formation of a kissing complex intermediate, which is converted to a more stable extended duplex conformation in the presence of the core protein. Mutations in the dimer linkage sequence loop sequence that prevent RNA dimerization in vitro significantly reduced but did not completely ablate the ability of HCV RNA to replicate or produce infectious virus in transfected cells. PMID- 20360392 TI - The requirement for the highly conserved G-1 residue of Saccharomyces cerevisiae tRNAHis can be circumvented by overexpression of tRNAHis and its synthetase. AB - Nearly all tRNA(His) species have an additional 5' guanine nucleotide (G(-1)). G( 1) is encoded opposite C(73) in nearly all prokaryotes and in some archaea, and is added post-transcriptionally by tRNA(His) guanylyltransferase (Thg1) opposite A(73) in eukaryotes, and opposite C(73) in other archaea. These divergent mechanisms of G(-1) conservation suggest that G(-1) might have an important cellular role, distinct from its role in tRNA(His) charging. Thg1 is also highly conserved and is essential in the yeast Saccharomyces cerevisiae. However, the essential roles of Thg1 are unclear since Thg1 also interacts with Orc2 of the origin recognition complex, is implicated in the cell cycle, and catalyzes an unusual template-dependent 3'-5' (reverse) polymerization in vitro at the 5' end of activated tRNAs. Here we show that thg1-Delta strains are viable, but only if histidyl-tRNA synthetase and tRNA(His) are overproduced, demonstrating that the only essential role of Thg1 is its G(-1) addition activity. Since these thg1 Delta strains have severe growth defects if cytoplasmic tRNA(His) A(73) is overexpressed, and distinct, but milder growth defects, if tRNA(His) C(73) is overexpressed, these results show that the tRNA(His) G(-1) residue is important, but not absolutely essential, despite its widespread conservation. We also show that Thg1 catalyzes 3'-5' polymerization in vivo on tRNA(His) C(73), but not on tRNA(His) A(73), demonstrating that the 3'-5' polymerase activity is pronounced enough to have a biological role, and suggesting that eukaryotes may have evolved to have cytoplasmic tRNA(His) with A(73), rather than C(73), to prevent the possibility of 3'-5' polymerization. PMID- 20360393 TI - Comparing RNA secondary structures using a relaxed base-pair score. AB - The use of free energy-based algorithms to compute RNA secondary structures produces, in general, large numbers of foldings. Recent research has addressed the problem of grouping structures into a small number of clusters and computing a representative folding for each cluster. At the heart of this problem is the need to compute a quantity that measures the difference between pairs of foldings. We introduce a new concept, the relaxed base-pair (RBP) score, designed to give a more biologically realistic measure of the difference between structures than the base-pair (BP) metric, which simply counts the number of base pairs in one structure but not the other. The degree of relaxation is determined by a single relaxation parameter, t. When t = 0, (no relaxation) our method is the same as the BP metric. At the other extreme, a very large value of t will give a distance of 0 for identical structures and 1 for structures that differ. Scores can be recomputed with different values of t, at virtually no extra computation cost, to yield satisfactory results. Our results indicate that relaxed measures give more stable and more meaningful clusters than the BP metric. We also use the RBP score to compute representative foldings for each cluster. PMID- 20360394 TI - Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing. AB - Yeast and human Tgs1 are orthologous RNA cap (guanine-N2) methyltransferases that convert m(7)G caps into the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal snRNAs. TMG caps are dispensable for vegetative yeast growth, but are essential in the absence of Mud2, the putative yeast homolog of human splicing factor U2AF. Here we exploited the synthetic lethal interactions of tgs1Delta and mud2Delta mutations to identify essential structural features of the Tgs1 and Mud2 proteins. Thirty-two new mutations were introduced into human Tgs1 and surveyed for their effects on function in vivo in yeast and on the two sequential guanine-N2 methylation reactions in vitro. The structure-function data highlight a strictly essential pi-cation interaction between Trp766 and the m(7)G base and a network of important enzymic contacts to the cap triphosphate via Lys646, Tyr771, Arg807, and Lys836. Mud2 is a 527-amino acid polypeptide composed of a hydrophilic N-terminal domain and a C-terminal RRM domain. We found that the RRM domain is necessary but not sufficient for Mud2 function in complementing growth of tgs1Delta mud2Delta and mud1Delta mud2Delta strains. Other changes in Mud2 elicited distinct phenotypes in tgs1Delta versus mud1Delta backgrounds. mud2Delta also caused a severe growth defect in cells lacking the Tgs1-binding protein encoded by the nonessential gene YNR004w (now renamed SWM2, synthetic with mud2Delta). Mud2 mutational effects in the swm2Delta background paralleled those for mud1Delta. The requirements for Mud2 function are apparently more stringent when yeast cells lack TMG caps than when they lack Mud1 or Swm2. PMID- 20360396 TI - Predominance of an ST11 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae clone causing bacteraemia and urinary tract infections in Korea. AB - To investigate the antimicrobial resistance, extended-spectrum beta-lactamases (ESBLs) and clones of Klebsiella pneumoniae isolates causing bacteraemia or urinary tract infection (UTI) in Korea, a total of 406 K. pneumoniae isolates from patients with bacteraemia (221 isolates) and UTI (185 isolates) were collected from 10 tertiary-care Korean hospitals from July 2006 to October 2007. In vitro antimicrobial susceptibility testing was performed for all isolates and ESBL production was tested. Multilocus sequence typing (MLST) analyses were performed to characterize genotypes of ESBL-producing K. pneumoniae isolates. PFGE was performed for sequence type 11 (ST11) isolates. Forty-seven UTI isolates (25.4 %) produced ESBLs, while 30 bacteraemia isolates (13.6 %) produced ESBLs (P=0.002). Among 77 ESBL-producing isolates, thirty-two (41.6 %) produced SHV type ESBLs. bla(CTX-M) genes such as bla(CTX-M-14) and bla(CTX-M-15) were detected in 36.4 %. MLST and PFGE analyses showed that ST11 was dominant in ESBL producing K. pneumoniae isolates causing UTI (57.4 %) and in those causing bacteraemia (70.0 %) and has been prevalent in Korean hospitals. ST11 isolates harbour a combination of different ESBL genes. The ST11 clone of ESBL-producing K. pneumoniae isolates prevails in Korea, but most isolates might acquire ESBL genes independently or several different clones might be distributed in Korea. PMID- 20360395 TI - Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. AB - RNA abundance and DNA copy number are routinely measured in high-throughput using microarray and next-generation sequencing (NGS) technologies, and the attributes of different platforms have been extensively analyzed. Recently, the application of both microarrays and NGS has expanded to include microRNAs (miRNAs), but the relative performance of these methods has not been rigorously characterized. We analyzed three biological samples across six miRNA microarray platforms and compared their hybridization performance. We examined the utility of these platforms, as well as NGS, for the detection of differentially expressed miRNAs. We then validated the results for 89 miRNAs by real-time RT-PCR and challenged the use of this assay as a "gold standard." Finally, we implemented a novel method to evaluate false-positive and false-negative rates for all methods in the absence of a reference method. PMID- 20360397 TI - Nosocomial infection by VIM-2 metallo-beta-lactamase-producing Pseudomonas putida. AB - Nosocomial infections caused by multidrug-resistant and carbapenem-resistant Pseudomonas putida isolates have been reported occasionally in severely ill or immunocompromised patients. Here we report the microbiological characteristics of what are believed to be the two first carbapenem-resistant VIM metallo-beta lactamase (MBL)-producing P. putida strains in Spain, which were isolated from patients at the University Hospital Complex of Santiago de Compostela. Both patients were immunocompromised with severe underlying diseases and had been hospitalized for more than 15 days. One of them had previously been treated with a broad-spectrum therapy. Antimicrobial susceptibility testing showed that both strains were resistant to piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, gentamicin, tobramycin, aztreonam, trimethoprim/sulfamethoxazole and ciprofloxacin, but sensitive to amikacin and colistin. For both isolates PCR and sequencing was positive for the bla(VIM-2) gene. Fingerprinting analysis revealed these were two different strains. One patient recovered clinically and one died; no direct link could be established between the isolation of P. putida and death. Our data expose the emergence of multidrug-resistant P. putida VIM-2 MBL, probably arising by independent horizontal transfer of resistance genes. So, although P. putida is not frequently isolated, it may survive easily in the hospital setting and occasionally cause difficult-to-treat nosocomial infections in severely ill patients. PMID- 20360398 TI - Identification of molecularly defined Staphylococcus aureus strains using matrix assisted laser desorption/ionization time of flight mass spectrometry and the Biotyper 2.0 database. AB - Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) has recently been introduced for bacterial identification. To our knowledge, this is the first study where the Biotyper 2.0 database (Bruker Daltonics) has been applied for bacterial identification in a local strain collection of molecularly defined Staphylococcus aureus. We showed that the accuracy of the Biotyper 2.0-based identification for 602 molecularly defined strains of S. aureus, irrespective of meticillin resistance, was equivalent to that of the molecularly defined reference even at a score cut-off value of 2. Also, 412 isolates of 20 different species of non-S. aureus staphylococci were all correctly identified to species level compared to the molecularly defined reference. Moreover, the MALDI-TOF MS-based S. aureus identification approach was clearly faster than more time-consuming methods such as a molecular identification approach. PMID- 20360399 TI - Differential roles for NOD2 in osteoblast inflammatory immune responses to bacterial pathogens of bone tissue. AB - Osteoblasts produce an array of immune molecules following bacterial challenge that can contribute to inflammation and the recruitment of leukocytes to sites of infection during bone diseases such as osteomyelitis. However, the mechanisms by which osteoblasts perceive and respond to facultative intracellular pathogens such as Salmonella species and Staphylococcus aureus have not been determined. Recently, our laboratory has described the expression in osteoblasts of members of the nucleotide-binding domain leucine-rich repeat region containing family of proteins that include nucleotide-binding oligomerization domain-2 (NOD2), a molecule that functions as an intracellular receptor for bacterial peptidoglycans. In the present study, we demonstrate that NOD2 expression is required for select inflammatory mediator production by osteoblasts following infection with the invasive pathogen Salmonella. In contrast, we have found that the inflammatory immune responses of osteoblasts to the passively internalized bacterial species Staphylococcus aureus, heat-killed pathogenic Salmonella, a non invasive Salmonella strain and specific Toll-like receptor ligands are not reduced in the absence of NOD2 expression but are, in fact, elevated. Based upon these findings, we suggest that NOD2 serves differential roles in osteoblasts, promoting inflammatory responses to invasive bacteria while tempering cell responses to extracellular and/or passively internalized bacterial species. PMID- 20360400 TI - Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in the IL-7 signaling pathway in B lymphoblastic lymphomas. AB - IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs. PMID- 20360401 TI - Distinct roles of complement receptor 3, Dectin-1, and sialic acids in murine macrophage interaction with Histoplasma yeast. AB - The yeast cells of dimorphic fungal pathogen Histoplasma reside primarily within the macrophages of an infected host; the interaction between the yeast and macrophage has a profound impact on host defense against the fungus. We used blocking antibodies and saccharides to identify the receptors that participate in the phagocytosis of and the cytokine response to Histoplasma. The phagocytosis and cytokine response results show that sialic acids on the macrophages were involved in the interaction between macrophages and Histoplasma. CR3, although not the only receptor involved, was responsible for phagocytosis and cytokine response. It is unclear which receptors other than CR3 are responsible for phagocytosis, but we did rule out the participation of TLR2, TLR4, MR, DC SIGN/SIGNR1, FcgammaR, VLA-5, and Dectin-1. Even though Dectin-1 did not participate in phagocytosis, it collaborated with CR3 in the cytokine response to Histoplasma, suggesting that in the presence of phagocytic receptors, Histoplasma triggers cytokine signals through Dectin-1. Moreover, macrophage phagocytosis of and cytokine response to Histoplasma are Syk kinase-dependent. Our study delineated the distinct roles of CR3, Dectin-1, and sialic acids in the interaction with Histoplasma and suggested that multiple receptor use might be important to host defense against Histoplasma. PMID- 20360402 TI - Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. AB - A cardinal feature of inflammation is the tissue recruitment of leukocytes, a process that is mediated predominantly by chemokines via their receptors on migrating cells. CCR2 and CCR5, two CC chemokine receptors, are important players in the trafficking of monocytes/macrophages and in the functions of other cell types relevant to disease pathogenesis. This review provides a brief overview of the biological actions of CCR2 and CCR5 and a comprehensive summary of published data that demonstrate the involvement of both receptors in the pathogenesis of immunologic diseases (RA, CD, and transplant rejection) and cardiovascular diseases (atherosclerosis and AIH). In light of the potential for functional redundancy of chemokine receptors in mediating leukocyte trafficking and the consequent concern over insufficient efficacy offered by pharmacologically inhibiting one receptor, this review presents evidence supporting dual targeting of CCR2 and CCR5 as a more efficacious strategy than targeting either receptor alone. It also examines potential safety issues associated with such dual targeting. PMID- 20360403 TI - Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation. AB - Alveolar macrophages and BDMCs undergo sequential biochemical changes during the chronic inflammatory response to chemically induced lung carcinogenesis in mice. Herein, we examine two chronic lung inflammation models-repeated exposure to BHT and infection with Mycobacterium tuberculosis-to establish whether similar macrophage phenotype changes occur in non-neoplastic pulmonary disease. Exposure to BHT or M. tuberculosis results in pulmonary inflammation characterized by an influx of macrophages, followed by systemic effects on the BM and other organs. In both models, pulmonary IFN-gamma and IL-4 production coincided with altered polarization of alveolar macrophages. Soon after BHT administration or M. tuberculosis infection, IFN-gamma content in BALF increased, and BAL macrophages became classically (M1) polarized, as characterized by increased expression of iNOS. As inflammation progressed in both models, the amount of BALF IFN-gamma content and BAL macrophage iNOS expression decreased, and BALF IL-4 content and macrophage arginase I expression rose, indicating alternative/M2 polarization. Macrophages present in M. tuberculosis-induced granulomas remained M1-polarized, implying that these two pulmonary macrophage populations, alveolar and granuloma associated, are exposed to different activating cytokines. BDMCs from BHT-treated mice displayed polarization profiles similar to alveolar macrophages, but BDMCs in M. tuberculosis-infected mice did not become polarized. Thus, only alveolar macrophages in these two models of chronic lung disease exhibit a similar progression of polarization changes; polarization of BDMCs was specific to BHT induced pulmonary inflammation, and polarization of granuloma macrophages was specific to the M. tuberculosis infection. PMID- 20360404 TI - Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synergy. AB - Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the expression of costimulatory molecules remained unchanged. Consequently, synergistic activation of DC did not affect their ability to induce T cell proliferation but resulted in T(H)1-biased responses in vitro and in vivo. Furthermore, we examined the impact of TLR ligand combinations on primary DC in vitro but observed only modest effects with a combination of CpG + Poly (I:C). However, noticeable synergy in terms of IL-12 production by DCs was detectable in vivo after systemic administration of CpG + Poly (I:C). Finally, we show that synergy is partially dependent on IFNAR signaling but does not require the release of IFNs to the enviroment, suggesting an autocrine action of type I IFNs. PMID- 20360405 TI - Adipose tissue macrophages: their role in adipose tissue remodeling. AB - The adipose tissue secretes a large number of bioactive substances, adipocytokines, which may be involved in a variety of physiologic and pathologic processes. Unbalanced production of pro- and anti-inflammatory adipocytokines seen in visceral fat obesity contributes critically to the development of the metabolic syndrome. Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation, suggesting that inflammation may be a potential mechanism, whereby obesity leads to insulin resistance. Indeed, obese adipose tissue is characterized by adipocyte hypertrophy, followed by increased angiogenesis, immune cell infiltration, extracellular matrix overproduction, and thus, increased production of proinflammatory adipocytokines during the progression of chronic inflammation. The dynamic change found in the adipose tissue can be referred to as "adipose tissue remodeling," in which stromal cells change dramatically in number and cell type during the course of obesity. Among stromal cells, infiltration of macrophages in the adipose tissue precedes the development of insulin resistance in animal models, suggesting that they are crucial for obesity-related adipose tissue inflammation. We have demonstrated that a paracrine loop involving saturated fatty acids and TNF-alpha derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for TLR4 complex, thereby activating macrophages. Understanding the molecular mechanism underlying adipose tissue remodeling may lead to the identification of novel, therapeutic strategies to prevent or treat obesity-induced adipose tissue inflammation. PMID- 20360406 TI - Diagnosis and management of dengue fever in children. PMID- 20360407 TI - Acute abdominal pain. PMID- 20360408 TI - Intimate partner violence. PMID- 20360409 TI - Patient safety and quality improvement: medical errors and adverse events. PMID- 20360410 TI - Pediatrics in the community: integrating community pediatrics into residency training. PMID- 20360411 TI - Research and statistics: understanding and identifying bias in research studies. PMID- 20360412 TI - Ethics for the pediatrician: pediatric research ethics: evolving principles and practices. PMID- 20360413 TI - Index of suspicion. PMID- 20360414 TI - Adenovirus. PMID- 20360415 TI - Toxic plants. PMID- 20360416 TI - Should the American Academy of Pediatrics respiratory syncytial virus guidelines be modified? PMID- 20360420 TI - A case of papillary squamous cell carcinoma of the uterine cervix. PMID- 20360421 TI - Comparison of time trends in gallbladder cancer mortality (1990-2006) between countries based using the WHO mortality database. PMID- 20360422 TI - Similar metabolic perturbations during all-out and constant force exhaustive exercise in humans: a (31)P magnetic resonance spectroscopy study. AB - It is not possible to attain a metabolic steady state during exercise above the so-called critical force or critical power. We tested the hypothesis that the muscle metabolic perturbations at the end of a bout of maximal isometric contractions, which yield a stable end-test force (equal to the critical force), would be similar to that at task failure following submaximal contractions performed above the critical force. Eight healthy subjects (four female) performed isometric single knee-extension exercise in the bore of a 1.5 T superconducting magnet on two occasions. Following familiarization, subjects performed the following exercises: (1) 60 maximal contractions (3 s contraction, 2 s rest); and (2) submaximal contractions (the same contraction regime performed at 54 +/- 8% maximal voluntary contraction) to task failure. Phosphocreatine (PCr), inorganic phosphate (P(i)) and diprotonated phosphate (H(2)PO(4)()) concentrations and pH were determined using (31)P magnetic resonance spectroscopy throughout both tests. During the maximal contractions, force production fell from 213 +/- 33 N to reach a plateau in the last 30 s of the test at 100 +/- 20 N. The muscle metabolic responses at the end of each test were substantial, but not different between conditions: [PCr] was reduced (to 21 +/- 12 and 17 +/- 7% of baseline for maximal and submaximal contractions, respectively; P = 0.17), [P(i)] was elevated (to 364 +/- 98 and 363 +/- 135% of baseline, respectively; P = 0.98) and pH reduced (to 6.64 +/- 0.16 and 6.69 +/- 0.17, respectively; P = 0.43). The [H(2)PO(4)()] was also elevated at the end of both tests (to 607 +/- 252 and 556 +/- 269% of baseline, respectively; P = 0.22). These data suggest that the exercise-induced metabolic perturbations contributing to force depression in all-out exercise are the same as those contributing to task failure during submaximal contractions. PMID- 20360423 TI - Telemetry in a motion-sickness model implicates the abdominal vagus in motion induced gastric dysrhythmia. AB - In humans, motion sickness is associated with disruption of normal gastric myoelectric activity, and it has been proposed that this results from an imbalance of autonomic nervous system activity. We used the established Suncus murinus (house musk shrew) model of motion-induced emesis to investigate the effect of horizontal motion on gastric myoelectric activity (recorded using telemetry) and the involvement of the abdominal vagi. Surgical vagotomy increased baseline dysrhythmia and reduced the dominant power of the gastric myoelectric signals. In response to motion, normal gastric myoelectric activity was reduced in sham-operated animals but not in vagotomized animals. Vagotomy, however, failed to affect motion-induced emesis. In conclusion, motion had a differential effect in sham-operated and vagotomized animals, which is consistent with the hypothesis that motion-induced dysrhythmia arises from an autonomic nervous system imbalance. PMID- 20360424 TI - Neurotransmitter and neuromodulatory mechanisms at peripheral arterial chemoreceptors. AB - The control of breathing depends critically on sensory inputs to the central pattern generator of the brainstem, arising from peripheral arterial chemoreceptors located principally in the carotid bodies (CBs). The CB receptors, i.e. glomus or type I cells, are excited by chemical stimuli in arterial blood, particularly hypoxia, hypercapnia, acidosis and low glucose, which initiate corrective reflex cardiorespiratory and cardiovascular adjustments. Type I cells occur in clusters and are innervated by petrosal afferent fibres. Synaptic specializations (both chemical and electrical) occur between type I cells and petrosal terminals, and between neighbouring type I cells. This, together with the presence of a wide array of neurotransmitters and neuromodulators linked to both ionotropic and metabotropic receptors, allows for a complex modulation of CB sensory output. Studies in several laboratories over the last 20 years have provided much insight into the transduction mechanisms. More recent studies, aided by the development of a co-culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response. This review highlights some of these developments, which have contributed to our current understanding of information processing at CB chemoreceptors. PMID- 20360425 TI - Ciliary beat frequency controlled by oestradiol and progesterone during ovarian cycle in guinea-pig Fallopian tube. AB - The ciliary beat frequency (CBF) of guinea-pig fimbria during the ovarian cycle was measured by video microscopy using a high-speed camera (500 Hz). In the follicular phase, with increasing concentrations of beta-oestradiol ([betaE(2)]) and a low concentration of progesterone ([PRG]), CBF increased from 13.5 to 16 Hz. In the ovulatory phase, with further increase of [betaE(2)], CBF decreased gradually from 16 to 13.5 Hz. In the early luteal phase, with low [PRG] and [betaE(2)], CBF increased to 17 Hz; however, in the middle luteal phase, with increasing [PRG], CBF decreased (12 Hz), and in the late luteal phase, with decreasing [PRG], CBF increased to 15 Hz. Then, in the resting phase, with low [betaE(2)] and [PRG], CBF decreased immediately to 14 Hz. The CBF of the fimbria was measured in guinea-pigs treated with beta-oestradiol benzoate (betaE(2)B) or medroxyprogesterone (mPRG). A low dose of betaE(2)B increased CBF to 14.5 Hz, whereas a high dose decreased it to 11 Hz. A betaE(2) receptor blocker, ICI 182,780, abolished the betaE(2)B-induced CBF changes and maintained CBF at 12.0 Hz. Medroxyprogesterone decreased CBF to 12.5 Hz, and mifepristone (a PRG receptor blocker) abolished the mPRG-induced CBF decrease and maintained CBF at 15 Hz. The addition of both blockers increased CBF to 18 Hz, suggesting that activation of betaE(2) or PRG receptors decreases the CBF of the fimbria. In conclusion, a moderate [betaE(2)] increase maintains a high CBF (15.5 Hz) in the follicular phase, and then further [betaE(2)] increase decreases CBF to 13.5 Hz in the ovulatory phase. In the early and late luteal phase, low [betaE(2)] and [PRG] increase CBF to 17 and 15 Hz, respectively, and in the middle luteal phase a high [PRG] decreases CBF (to 12 Hz). Thus, the CBF of the fimbria was controlled by signals via betaE(2) and PRG receptors in guinea-pigs. PMID- 20360426 TI - Scrub typhus: an unrecognized threat in South India - clinical profile and predictors of mortality. AB - Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus. PMID- 20360427 TI - Primary thromboprophylaxis in the palliative care setting: a qualitative systematic review. AB - Symptomatic venous thromboembolism (VTE) occurs in 15% of patients with advanced malignancy. Primary thromboprophylaxis using low-molecular-weight heparin (LMWH) is supported by Level 1A evidence but is under-utilized in the palliative setting. A systematic search was performed of Medline, Cochrane Library, EMBASE, AMED, and Web of Science for papers published between 1960 and January 2010 using search terms: 'palliative', 'thromboprophylaxis', 'thromboembolism', 'heparin', and 'advanced cancer'. Forty-two citations were obtained, of which 34 were excluded as they dealt with treatment of VTE, novel anticoagulants, or LMWH as a cancer treatment. Eight original articles were reviewed independently by two authors. Data was extracted according to a predetermined questionnaire. Studies examined practice in specialist palliative care (SPC) units, and attitudes held by a total of 32 physicians and 198 patients. Patients find LMWH acceptable, particularly patients who experienced a sudden decline in performance status. Reluctance to prescribe LMWH is based on physicians' concerns regarding negative impact on quality of life, and lack of evidence specific to the palliative care setting. In conclusion, LMWH prophylaxis should be implemented in patients with a previously good performance status who have a transiently increased risk of VTE and no contraindications. Further research is required using outcome measures specific to palliative care. PMID- 20360428 TI - Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice. AB - Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30-50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50-75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor alpha coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30-78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency (P=0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function. PMID- 20360429 TI - Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans. AB - Chronic systemic platelet cyclooxygenase (COX) inhibition with low-dose aspirin [acetylsalicylic acid (ASA)] significantly attenuates reflex cutaneous vasodilation in middle-aged humans, whereas acute, localized, nonisoform-specific inhibition of vascular COX with intradermal administration of ketorolac does not alter skin blood flow during hyperthermia. Taken together, these data suggest that platelets may be involved in reflex cutaneous vasodilation, and this response is inhibited with systemic pharmacological platelet inhibition. We hypothesized that, similar to ASA, specific platelet ADP receptor inhibition with clopidogrel would attenuate reflex vasodilation in middle-aged skin. In a double blind crossover design, 10 subjects (53+/-2 yr) were instrumented with four microdialysis fibers for localized drug administration and heated to increase body core temperature [oral temperature (Tor)] 1 degrees C during no systemic drug (ND), and after 7 days of systemic ASA (81 mg) and clopidogrel (75 mg) treatment. Skin blood flow (SkBF) was measured using laser-Doppler flowmetry over each site assigned as 1) control, 2) nitric oxide synthase inhibited (NOS-I; 10 mM NG-nitro-L-arginine methyl ester), 3) COX inhibited (COX-I; 10 mM ketorolac), and 4) NOS-I+COX-I. Data were normalized and presented as a percentage of maximal cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside+local heating to 43 degrees C). During ND conditions, SkBF with change (Delta) in Tor=1.0 degrees C was 56+/-3% CVCmax. Systemic low-dose ASA and clopidogrel both attenuated reflex vasodilation (ASA: 43+/-3; clopidogrel: 32+/-3% CVCmax; both P<0.001). In all trials, localized COX-I did not alter SkBF during significant hyperthermia (ND: 56+/-7; ASA: 43+/-5; clopidogrel: 35+/-5% CVCmax; all P>0.05). NOS-I attenuated vasodilation in ND and ASA (ND: 28+/-6; ASA: 25+/-4% CVCmax; both P<0.001), but not with clopidogrel (27+/-4% CVCmax; P>0.05). NOS-I+COX-I was not different compared with NOS-I alone in either systemic treatment condition. Both systemic ASA and clopidogrel reduced the time required to increase Tor 1 degrees C (ND: 58+/-3 vs. ASA: 45+/-2; clopidogrel: 39+/-2 min; both P<0.001). ASA-induced COX and specific platelet ADP receptor inhibition attenuate reflex vasodilation, suggesting platelet involvement in reflex vasodilation through the release of vasodilating factors. PMID- 20360430 TI - Sleep state dependence of ventilatory long-term facilitation following acute intermittent hypoxia in Lewis rats. AB - Ventilatory long-term facilitation (vLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH). Although vLTF has been reported in unanesthetized animals, little is known concerning the effects of vigilance state on vLTF expression. We hypothesized that AIH-induced vLTF is preferentially expressed in sleeping vs. awake male Lewis rats. Vigilance state was assessed in unanesthetized rats with chronically implanted EEG and nuchal EMG electrodes, while tidal volume, frequency, minute ventilation (Ve), and CO(2) production were measured via plethysmography, before, during, and after AIH (five 5-min episodes of 10.5% O(2) separated by 5-min normoxic intervals), acute sustained hypoxia (25 min of 10.5% O(2)), or a sham protocol without hypoxia. Vigilance state was classified as quiet wakefulness (QW), light and deep non-rapid eye movement (NREM) sleep (l-NREM and d-NREM sleep, respectively), or rapid eye movement sleep. Ventilatory variables were normalized to pretreatment baseline values in the same vigilance state. During d-NREM sleep, vLTF was observed as a progressive increase in Ve post-AIH (27 + or - 5% average, 30-60 min post-AIH). In association, Ve/Vco(2) (36 + or - 2%), tidal volume (14 + or - 2%), and frequency (7 + or - 2%) were increased 30-60 min post-AIH during d-NREM sleep. vLTF was significant but less robust during l-NREM sleep, was minimal during QW, and was not observed following acute sustained hypoxia or sham protocols in any vigilance state. Thus, vLTF is state-dependent and pattern-sensitive in unanesthetized Lewis rats, with the greatest effects during d-NREM sleep. Although the physiological significance of vLTF is not clear, its greatest significance to ventilatory control is most likely during sleep. PMID- 20360431 TI - Heterochromatin dysregulation in human diseases. AB - Heterochromatin is a repressive chromatin state that is characterized by densely packed DNA and low transcriptional activity. Heterochromatin-induced gene silencing is important for mediating developmental transitions, and in addition, it has more global functions in ensuring chromosome segregation and genomic integrity. Here we discuss how altered heterochromatic states can impair normal gene expression patterns, leading to the development of different diseases. Over the last years, therapeutic strategies that aim toward resetting the epigenetic state of dysregulated genes have been tested. However, due to the complexity of epigenetic gene regulation, the "first-generation drugs" that function globally by inhibiting epigenetic machineries might also introduce severe side effects. Thus detailed understanding of how repressive chromatin states are established and maintained at specific loci will be fundamental for the development of more selective epigenetic treatment strategies in the future. PMID- 20360434 TI - Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. AB - Our previous study reported that metabolic stress in skeletal muscle achieved by combining moderate blood flow restriction (BFR) with low-intensity resistance exercise at 20% of one repetition maximum (1 RM) could not reach the level achieved by high-intensity resistance exercise. Since the previous protocol is typical of current regimens of this type, we sought in this study to optimize the exercise protocol for low-intensity resistance exercise with BFR by examining the dose effects of exercise intensity and pressure. Twelve healthy subjects participated in this study. They were asked to perform unilateral plantar flexion for 2 min (30 repetitions/min) under six different conditions: two resistance exercises (20% 1 RM and 65% 1 RM) without BFR, and four BFR protocols. The four BFR protocols included three different exercise intensities (20, 30, and 40% 1 RM) with moderate pressure (MP) using 130% of systolic blood pressure (147+/-17 mmHg, mean+/-SD) and 20% 1 RM with high pressure at 200 mmHg. Intramuscular metabolites and pH were obtained by 31P-magnetic resonance spectroscopy. Significant dose effects on intramuscular metabolites and pH were observed for exercise intensity (P<0.001) but not for BFR pressure. The BFR protocol combining 30% 1 RM with MP had similar results as the high-intensity load at 65% 1 RM. Intramuscular metabolic stress during BFR exercise might be susceptible to increasing exercise intensity. To replace high-intensity resistance exercise, the BFR protocol might require an intensity of >or=30% 1 RM. PMID- 20360433 TI - The innervation and organization of motor units in a series-fibered human muscle: the brachioradialis. AB - We studied the innervation and organization of motor units in the brachioradialis muscle of 25 normal human subjects. We recorded intramuscular EMG signals at points separated by 15 mm along the proximodistal muscle axis during moderate isometric contractions, identified from 27 to 61 (mean 39) individual motor units per subject using EMG decomposition, and estimated the locations of the endplates and distal muscle/tendon junctions from the motor-unit action potential (MUAP) propagation patterns and terminal standing waves. In three subjects all the motor units were innervated in a single endplate zone. In the other 22 subjects, the motor units were innervated in 3-6 (mean 4) distinct endplate zones separated by 15-55 mm along the proximodistal axis. One-third of the motor units had fibers innervated in more than one zone. The more distally innervated motor units had distinct terminal waves indicating tendonous termination, while the more proximal motor units lacked terminal waves, indicating intrafascicular termination. Analysis of blocked MUAP components revealed that 19% of the motor units had at least one doubly innervated fiber, i.e., a fiber innervated in two different endplate zones by two different motoneurons, and thus belonging to two different motor units. These results are consistent with the brachioradialis muscle having a series-fibered architecture consisting of multiple, overlapping bands of muscle fibers in most individuals and a simple parallel-fibered architecture in some individuals. PMID- 20360432 TI - Respiratory and Mayer wave-related discharge patterns of raphe and pontine neurons change with vagotomy. AB - Previous models have attributed changes in respiratory modulation of pontine neurons after vagotomy to a loss of pulmonary stretch receptor "gating" of an efference copy of inspiratory drive. Recently, our group confirmed that pontine neurons change firing patterns and become more respiratory modulated after vagotomy, although average peak and mean firing rates of the sample did not increase (Dick et al., J Physiol 586: 4265-4282, 2008). Because raphe neurons are also elements of the brain stem respiratory network, we tested the hypotheses that after vagotomy raphe neurons have increased respiratory modulation and that alterations in their firing patterns are similar to those seen for pontine neurons during withheld lung inflation. Raphe and pontine neurons were recorded simultaneously before and after vagotomy in decerebrated cats. Before vagotomy, 14% of 95 raphe neurons had increased activity during single respiratory cycles prolonged by withholding lung inflation; 13% exhibited decreased activity. After vagotomy, the average index of respiratory modulation (eta(2)) increased (0.05 +/ 0.10 to 0.12 +/- 0.18 SD; Student's paired t-test, P < 0.01). Time series and frequency domain analyses identified pontine and raphe neuron firing rate modulations with a 0.1-Hz rhythm coherent with blood pressure Mayer waves. These "Mayer wave-related oscillations" (MWROs) were coupled with central respiratory drive and became synchronized with the central respiratory rhythm after vagotomy (7 of 10 animals). Cross-correlation analysis identified functional connectivity in 52 of 360 pairs of neurons with MWROs. Collectively, the results suggest that a distributed network participates in the generation of MWROs and in the coordination of respiratory and vasomotor rhythms. PMID- 20360435 TI - Locomotor activity and gait in aged mice deficient for type IX collagen. AB - Osteoarthritis (OA) is a risk factor for physical inactivity and impaired mobility, but it is not well understood how these locomotor behaviors are affected by the age of onset of OA and disease severity. Male mice homozygous for a Col9a1 gene inactivation (Col9a1(-/-)) develop early onset knee OA, increased tactile pain sensitivity, and gait alterations by 9 mo of age. We hypothesized that aged Col9a1(-/-) mice would reduce joint pain by adopting locomotor behaviors that reduce both the magnitude and daily frequency of joint loading. We tested this hypothesis by evaluating gait and spontaneous locomotor activity in 15- to 17-mo-old male Col9a1(-/-) (n = 5) and Col9a1(+/+)(WT) (n = 5) mice using well-controlled measures of voluntary activity in overground and running wheel conditions, as well as studies of gait in a velocity-controlled treadmill. We found no difference due to genotype in freely chosen locomotor velocity, stride frequency, hindfoot duty factor, dark phase activity time, or dark-phase travel distance during overground, running wheel, or speed-matched treadmill locomotion. Interpretation of these findings is potentially confounded by the observation that WT mice have greater knee OA than Col9a1(-/-) mice in the lateral tibial plateau by 17 mo of age. When accounting for individual differences in knee OA, functional locomotor impairments in aged Col9a1(-/-) and WT mice are manifested as reductions in total locomotor activity levels (e.g., both distance traveled and time active), particularly for wheel running. These results support the concept that current disease status, rather than age of disease onset, is the primary determinant of impaired locomotor activity with aging. PMID- 20360437 TI - An integrative model of motor unit activity during sustained submaximal contractions. AB - The purpose of the study was to expand a model of motor unit recruitment and rate coding (30) to simulate the adjustments that occur during a fatiguing contraction. The major new components of the model were the introduction of time varying parameters for motor unit twitch force, recruitment, discharge rate, and discharge variability, and a control algorithm that estimates the net excitation needed by the motoneuron pool to maintain a prescribed target force. The fatigue induced changes in motor unit activity in the expanded model are a function of changes in the metabolite concentrations that were computed with a compartment model of the intra- and extracellular spaces. The model was validated by comparing the simulation results with data available from the literature and experimentally recorded in the present study during isometric contractions of the first dorsal interosseus muscle. The output of the model was able to replicate a number of experimental findings, including the time to task failure for a range of target forces, the changes in motor unit discharge rates, the skewness and kurtosis of the interspike interval distributions, discharge variability, and the discharge characteristics of newly recruited motor units. The model output provides an integrative perspective of the adjustments during fatiguing contractions that are difficult to measure experimentally. PMID- 20360436 TI - Chronic hypercapnia alters lung matrix composition in mouse pups. AB - RATIONALE: permissive hypercapnia, a stretch-limiting ventilation strategy, often results in high Pa(CO(2)). This strategy is associated with reduced morbidity and mortality in premature infants and its benefits have been attributed to diminished barotrauma. However, little is known about the independent effect of high CO(2) levels during the lung development. METHODS: mice were exposed to 8% CO(2) or room air for 2 wk either from postnatal day 2 through 17 or as adults (approximately 2 mo of age). Lungs were excised and processed for protein, RNA, histology, and total lung volumes. RESULTS: histologic analysis demonstrated that alveolar walls of CO(2)-exposed mouse pups were thinner than those of controls and had twice the total lung volume. Molecular analysis revealed that several matrix proteins in the lung were downregulated in mouse pups exposed to hypercapnia. Interstitial collagen type I alpha1, type III alpha1, elastin and fibronectin protein, and mRNA levels were less than half of controls while collagen IV alpha 5 was unaffected. This decrease in interstitial collagen could thus account for the thinning of the interstitial matrix and the altered lung biomechanics. Matrix metalloproteinase (MMP)-8, a collagenase that has specificity for collagen types I and III, increased in hypercapnic mouse pups, suggesting increased collagen degradation. Moreover, tissue inhibitor of MMP (TIMP)-1, a potent inhibitor of MMP-8, was significantly decreased. However, unlike pups, adult mice exposed to hypercapnia demonstrated only a mild increase in total lung volumes and did not exhibit similar molecular or histologic changes. CONCLUSIONS: although permissive hypercapnia may prevent lung injury from barotrauma, our study revealed that exposure to hypercapnia may be an important factor in lung remodeling and function, especially in early life. PMID- 20360438 TI - Airway response to emotional stimuli in asthma: the role of the cholinergic pathway. AB - In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma. PMID- 20360439 TI - Rho kinase activation and ROS production contributes to the cooling enhanced contraction in cutaneous equine digital veins. AB - A decrease in environmental temperature can directly affect the contractility of cutaneous vasculature, mediated in part by alpha(2)-adrenoceptors. Most of the cellular mechanisms underlying the cooling-enhanced contractility to alpha(2) adrenoceptor agonists have been reported in cutaneous arteries but little information is available on cutaneous veins. To investigate the cellular mechanisms associated with the cooling-enhanced contraction to UK-14304 (alpha(2) adrenoceptor agonist), isolated equine digital veins (EDVs) were studied at 30 degrees C and 22 degrees C. The effects of inhibitors were studied on the contractile response to UK-14304 (0.1 microM). The cooling-enhanced responses were inhibited by Rho kinase inhibitors [maximum response to UK-14304 95.2 +/- 8% of response to depolarizing Krebs solution (DKS) in control vessels cooled to 22 degrees C, compared with 31.4 +/- 6% in the presence of fasudil 1 microM and 75.8 +/- 6% with Y-27632 0.1 microM] and the effects of these inhibitors were considerably less at 30 degrees C (control response 56.4 +/- 5% of DKS; 34.9 +/- 6% with fasudil 1 microM and 50.6 +/- 9% with Y-27632 0.1 microM). Furthermore, Western blotting showed that one of the downstream targets for Rho kinase activity, ezrin/radixin/moesin, was phosphorylated after cooling and reduced by fasudil (1 microM) only at 22 degrees C. The activation of protein kinase C contributed to the contractile response, but predominantly at 30 degrees C (maximum response 82.3 +/- 9% of DKS for control; 57.7 +/- 10% in the presence of chelerythrine 10 microM) with no significant effect at 22 degrees C. The reduction of the response at 22 degrees C by antioxidants, rotenone (14% reduction), and tempol (21% reduction) suggested the contribution of reactive oxygen species (ROS). No evidence was obtained to support the participation of tyrosine kinase. These data demonstrate that Rho kinase activation and the production of ROS contributes to the cooling-enhanced contraction in these cutaneous digital veins. PMID- 20360440 TI - Safety and barriers to care. PMID- 20360441 TI - Staff-perceived barriers and facilitators. PMID- 20360442 TI - Introduction. PMID- 20360443 TI - Introduction to progressive mobility. PMID- 20360444 TI - Continuous lateral rotation therapy. PMID- 20360445 TI - Tips for protecting critically ill patients from pressure ulcers. PMID- 20360446 TI - Using the beach chair position in ICU patients. PMID- 20360447 TI - Converting presentations into journal articles: a guide for nurses. PMID- 20360448 TI - Quality improvement in the catheterization laboratory: redesigning patient flow for improved outcomes. PMID- 20360449 TI - Changing the environment of care for patients with a pulmonary artery catheter. PMID- 20360450 TI - Undiagnosed pulmonary arterial hypertension at 33 weeks' gestation: a case report. PMID- 20360451 TI - Repair of ventricular aneurysm after stage I modified sano-norwood procedure. PMID- 20360452 TI - Identifying vulnerable patients at heightened risk for medical error. PMID- 20360453 TI - Stroke volume optimization versus central venous pressure in fluid management. PMID- 20360454 TI - Patient-directed music therapy as an adjunct during burn wound care. PMID- 20360456 TI - I am a critical care nurse. PMID- 20360457 TI - Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion. AB - The P2X(7) receptor is an ATP-gated cation channel expressed in immune cells and plays a role in proinflammatory cytokine release from monocytes and macrophages. This study investigated the coinheritance of 12 functionally relevant single nucleotide polymorphisms (SNPs) in the human P2X(7) gene (P2RX7), and the functional effect of each singly and in combination was assessed by measurements of ATP-induced currents and ethidium(+) uptake. Genotyping of 3430 Caucasian subjects identified 4 common haplotypes in addition to the common (wild-type) P2X(7)-1. Two haplotypes (denoted P2X(7)-2 and P2X(7)-4) contained various combinations of gain-of-function SNPs. P2X(7)-4 was identified uniquely by the Gln-460 to Arg polymorphism (rs2230912). When expressed in HEK-293 cells, recombinant P2X(7)-2, and P2X(7)-4 haplotypes displayed a 3-fold and 5-fold increase, respectively, in receptor function compared to the wild-type P2X(7)-1. Both P2X(7) haplotypes contained the Ala-348>Thr polymorphism (rs1718119), and this mutation was critical for the gain-of-function effect. Peripheral blood monocytes and erythrocytes from subjects homozygous for gain-of-function P2X(7) haplotypes exhibited increased ATP-induced ethidium(+) uptake and (86)Rb(+) efflux, respectively, and this correlated with increased IL-1beta secretion from LPS-primed monocytes. Inheritance of these P2X(7) haplotypes predisposing to increased proinflammatory cytokine secretion may be important in genetic association studies of inflammatory, infectious, and psychiatric disorders. PMID- 20360458 TI - Acoustic analysis of the voiced-voiceless distinction in Dutch tracheoesophageal speech. AB - PURPOSE: Confusions between voiced and voiceless plosives and voiced and voiceless fricatives are common in Dutch tracheoesophageal (TE) speech. This study investigates (a) which acoustic measures are found to convey a correct voicing contrast in TE speech and (b) whether different measures are found in TE speech than in normal laryngeal (NL) speech. The main focus was on plosives. METHOD: Nine TE and 5 NL speakers were included in this study. Fourteen acoustic measures were selected and analyzed. Comparisons were made between voiced and voiceless for the groups separately and between TE and NL speakers. Conditional inference trees were used to establish the most important distinguishing cue. RESULTS: TE speakers do not differ significantly from NL speakers, except for pitch-related measures. For plosives, all measures distinguished between voiced and voiceless for both speaker groups. The main distinguishing measure for the plosives was relative phonation time in the closure. CONCLUSIONS: TE and NL speakers differ less in the way the voiced-voiceless distinction is conveyed than expected. Further research is needed to show whether the main acoustic cue is also perceptually most relevant. PMID- 20360459 TI - Preschool speech, language skills, and reading at 7, 9, and 10 years: etiology of the relationship. AB - PURPOSE: To examine the etiology of the relationship between preschool speech and language, and later reading skills. METHOD: One thousand six hundred seventy-two children from the Twins Early Development Study (B. R. Oliver & R. Plomin, 2007) were given a comprehensive speech and language assessment at 4(1/2) years. Reading was assessed at 7, 9, and 10 years. Twin analyses were applied to the data to assess the contributions of genetic and environmental factors to the longitudinal relationships between speech and reading, and language and reading. RESULTS: Phenotypically, there is a moderate and stable relationship between 4(1/2)-year speech and language scores and reading at 7, 9, and 10 years. Etiologically, at the individual-differences level, both genetic and shared environmental factors contribute to the links between language skills and reading. By contrast, genetic factors account for most of the relationship between early speech and later reading. At the extremes, there appears to be an even stronger role for genetic factors in accounting for the prediction from early speech and language impairments to later reading outcome. CONCLUSION: Both genetic and environmental factors contribute to the relationship between early language skills and reading, whereas genetic factors play a dominant role in the relationship between early speech and reading. PMID- 20360460 TI - Mean length of utterance levels in 6-month intervals for children 3 to 9 years with and without language impairments. AB - PURPOSE: The mean length of children's utterances is a valuable estimate of their early language acquisition. The available normative data lack documentation of language and nonverbal intelligence levels of the samples. This study reports age referenced mean length of utterance (MLU) data from children with specific language impairment (SLI) and children without language impairments. METHOD: Of the 306 child participants drawn from a data archive, ages 2;6-9;0 (years;months), 170 were in the SLI group and 136 were in the control group. There were 1,564 spontaneous language samples collected, and these were transcribed and analyzed for sample size and MLU in words and morphemes. Means, standard deviations, and effect sizes for group differences are reported for MLUs, along with concurrent language and nonverbal intelligence assessments, per 6-month intervals. RESULTS: The results document an age progression in MLU words and morphemes and a persistent lower level of performance for children with SLI. CONCLUSION: The results support the reliability and validity of MLU as an index of normative language acquisition and a marker of language impairment. The findings can be used for clinical benchmarking of deficits and language intervention outcomes as well as for comparisons across research samples. PMID- 20360461 TI - Randomized comparison of augmented and nonaugmented language interventions for toddlers with developmental delays and their parents. AB - PURPOSE: This study compared the language performance of young children with developmental delays who were randomly assigned to 1 of 3 parent-coached language interventions. Differences in performance on augmented and spoken word size and use, vocabulary size, and communication interaction skills were examined. METHOD: Sixty-eight toddlers with fewer than 10 spoken words were randomly assigned to augmented communication input (AC-I), augmented communication output (AC-O), or spoken communication (SC) interventions; 62 children completed the intervention. This trial assessed the children's symbolic language performance using communication measures from the language transcripts of the 18th and 24th intervention sessions and coding of target vocabulary use. RESULTS: All children in the AC-O and AC-I intervention groups used augmented and spoken words for the target vocabulary items, whereas children in the SC intervention produced a very small number of spoken words. Vocabulary size was substantially larger for AC-O and AC-I than for SC groups. CONCLUSIONS: This study found that augmented language interventions that include parent coaching have a positive communication effect on young children with developmental delays who begin with fewer than 10 spoken words. Clinical implications suggest that augmented communication does not hinder, and actually aids, speech production abilities in young children with developmental delays. PMID- 20360462 TI - Relation of executive functioning to pragmatic outcome following severe traumatic brain injury. AB - PURPOSE: This study was designed to explore the behavioral nature of pragmatic impairment following severe traumatic brain injury (TBI) and to evaluate the contribution of executive skills to the experience of pragmatic difficulties after TBI. METHOD: Participants were grouped into 43 TBI dyads (TBI adults and close relatives) and 43 control dyads. All TBI participants had sustained severe injury (mean posttraumatic amnesia duration = 45.19 days, SD = 39.15) due to a moving vehicle-related trauma. A minimum of 2 years had elapsed since injury (M = 5.36 years, SD = 3.61). The La Trobe Communication Questionnaire (LCQ; Douglas, O'Flaherty, & Snow, 2000) was administered to all participants. Measures of executive function included the following: the FAS verbal fluency task (Spreen & Benton, 1969), the Speed and Capacity of Language Processing test (Baddeley, Emslie, & Nimmo-Smith, 1992), and the Rey Auditory Verbal Learning Task (Rey, 1964). RESULTS: Perceptions of TBI participants and their relatives were significantly correlated (r = .63, p < .001) and significantly different from those of controls, F(1, 84) = 37.2, p < .001. Pragmatic difficulties represented violations in 3 domains of Grice's (1975) Cooperative Principle (Quantity, Relation, and Manner), and executive function measures predicted 37% (32% adjusted) of the variability in LCQ scores. CONCLUSIONS: The study demonstrates evidence of a significant association between executive impairment and the pragmatic communication difficulties experienced by individuals with TBI. PMID- 20360464 TI - Production of tense morphology by Afrikaans-speaking children with and without specific language impairment. AB - PURPOSE: To establish whether the predictions of the extended optional infinitive (EOI) hypothesis (Rice, Wexler, & Cleave, 1995) hold for the language of Afrikaans-speaking children with specific language impairment (SLI) and whether tense marking is a possible clinical marker of SLI in Afrikaans. METHOD: Production of tense morphology was examined in 3 groups of Afrikaans-speaking children-15 with SLI who were 6 years old, 15 typically developing (TD) 4-year olds matched on mean length of utterance, and 15 TD 6-year-olds-using both elicited and spontaneously produced verb forms. RESULTS: On the sentence completion task, children with SLI fared on par with 4-year-olds and worse than age-matched peers. However, in terms of spontaneous production of morphemes pertaining to tense, children with SLI fared worse than both TD groups. Furthermore, children with SLI mostly made the same types of errors as 4-year olds, although some errors were unique to the SLI group. Most errors entailed omissions, of modal and temporal auxiliaries as well as of copula be. CONCLUSION: The errors offer support for the EOI hypothesis. Tense marking has the potential to be a clinical marker of SLI in Afrikaans, but further research with larger groups of Afrikaans-speaking children, including children of other ages, is needed to confirm this. PMID- 20360463 TI - Generalized motor abilities and timing behavior in children with specific language impairment. AB - PURPOSE: To examine whether children with specific language impairment (SLI) differ from normally developing peers in motor skills, especially those skills related to timing. METHOD: Standard measures of gross and fine motor development were obtained. Furthermore, finger and hand movements were recorded while children engaged in 4 different timing tasks, including tapping and drawing circles in time with a metronome or a visual target. Fourteen children with SLI (age 6 to 8 years) and 14 age-matched peers who were typically developing participated. RESULTS: As expected, children with SLI showed poorer performance on a standardized test of gross and fine motor skill than did their normally developing peers. However, timing skill in the manual domain was equivalent to that seen in typically developing children. CONCLUSIONS: Consistent with earlier findings, relatively poor gross and fine motor performance is observed in children with SLI. Surprisingly, rhythmic timing is spared. PMID- 20360465 TI - Identification of clinical markers of specific language impairment in adults. AB - PURPOSE: To investigate the usefulness of 3 tasks known to be effective diagnostic clinical markers of specific language impairment (SLI) in children: (a) nonword repetition, (b) sentence repetition, and (c) grammaticality judgments of finiteness marking. METHOD: Two groups of young adults, 13 with SLI and 18 with typical language, completed 3 experimental tasks: (a) nonword repetition, (b) sentence repetition, and (c) grammaticality judgments of sentences that were either correct or contained an omitted finiteness marker, an overt agreement error, or an omitted progressive -ing. Analyses included receiver operating characteristic curve analyses and computation of likelihood ratios associated with the use of each task as a clinical marker for SLI, as well as development of a logistic regression model that used multiple tasks as predictors. RESULTS: Each marker task significantly contributed to classification of adults as affected or unaffected by SLI, with moderate positive and negative likelihood ratios. A combination of the 3 marker tasks was the best predictor of affectedness status with moderate to large likelihood ratios. CONCLUSIONS: The results suggest that SLI persists into adulthood and that effective clinical markers of this disorder are similar to those used to identify SLI in children. Refinement of these tasks to increase their likelihood ratios will improve their usefulness in diagnosing SLI in adults. PMID- 20360466 TI - A treatment sequence for phonological alexia/agraphia. AB - PURPOSE: Damage to left perisylvian cortex often results in impaired phonological processing abilities with written language profiles consistent with phonological alexia and phonological agraphia. The purpose of this article was to examine a behavioral treatment sequence for such individuals intended to strengthen phonological processing and links between phonology and orthography, as well as train a means to maximize use of residual orthographic and phonological knowledge for spelling. METHOD: Two women with persistent impairments of written language and phonological processing following damage to left perisylvian cortical regions participated in this study. Both exhibited characteristic features of phonological alexia and agraphia in that reading and spelling performance for real words was better preserved than nonwords (lexicality effect). A 2-stage treatment protocol was administered to strengthen sublexical skills (phonological treatment) and to train interactive use of lexical and sublexical information to maximize spelling performance (interactive treatment). RESULTS: Both participants improved phonological processing abilities and reading/spelling via the sublexical route. They also improved spelling of real words and were able to detect and correct most residual errors using an electronic spelling aid. CONCLUSIONS: Behavioral treatment served to strengthen phonological skills supporting reading and spelling, and provided a functional compensatory strategy to overcome residual weaknesses. PMID- 20360467 TI - Reproduction of inflectional markers in French-speaking children with reading impairment. AB - PURPOSE: Children with reading impairment (RI) experience difficulties in oral and written production of inflectional markers. The origin of these difficulties is not well documented in French. According to some authors, acquisition of irregular items by typically developing children is predicted by token frequency, whereas acquisition of regular items is predicted by type frequency. The authors hypothesized that acquisition of inflectional markers in French depends on the distribution of irregular, invariable, and regular (transparent) items within a grammatical category. METHOD: Fifteen children with RI age matched with 15 children with typical reading development repeated and read aloud sentences containing adjectives inflected for gender and verbs inflected for number. Inflected adjectives and verbs were matched for token frequency and phonological complexity, whereas distribution of invariable, transparent, and irregular items differed within each grammatical category. RESULTS: Results show higher error rates in the RI group, who produced more errors in reading than repetition, and more errors on inflected verbs than adjectives. Error distribution varied with the proportion of invariable, irregular, and transparent items within each grammatical category, confirming the authors' hypothesis. CONCLUSION: The authors concluded that morphological difficulties of children with RI group originated from a delay in extracting systematicity in verb and adjective inflectional marking. PMID- 20360468 TI - The internal validity and acceptability of the Danish SI-3: a language-screening instrument for 3-year-olds. AB - PURPOSE: To document the development of a new parent- and day care-administered screening instrument (the Screening Instrument for 3-Year-Olds [SI-3]) to be used in a newly implemented, educationally motivated population language screening in Denmark. The authors investigated whether the basic principles of the SI-3 were working satisfactorily and studied the acceptability of the instrument. METHOD: To examine the general properties of the SI-3, 517 children from a population based sample were screened with the SI-3 instrument, which assesses various receptive and productive language dimensions on the basis of parental checklists and day care staff-administered structured tests. To examine the acceptability of the SI-3, 2 questionnaires were administered and completed by 291 parents and 135 preschool teachers. Result We obtained a distribution with sufficient negative skew to differentiate among children with low scores, and the instrument displayed acceptable psychometric properties for most subscales. Results of the acceptability study suggest that the acceptability of the SI-3 is high among parents and day care staff, which supports a high attendance rate. CONCLUSION: The SI-3 captures a variety of language skills and is good at differentiating children in the lower end of the tail; it is thereby suitable for population language screening, although results indicated the need for some revision. PMID- 20360469 TI - Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma. AB - Statin inhibitors, used to control hypercholesterolemia, trigger apoptosis of hematologic tumor cells and therefore have immediate potential as anticancer agents. Evaluations of statins in acute myelogenous leukemia and multiple myeloma have shown that statin efficacy is mixed, with only a subset of tumor cells being highly responsive. Our goal was to distinguish molecular features of statin sensitive and -insensitive myeloma cells and gain insight into potential predictive markers. We show that dysregulation of the mevalonate pathway is a key determinant of sensitivity to statin-induced apoptosis in multiple myeloma. In sensitive cells, the classic feedback response to statin exposure is lost. This results in deficient up-regulation of 2 isoforms of hydroxymethylglutaryl coenzyme A reductase: the rate-limiting enzyme of the mevalonate pathway and hydroxymethylglutaryl coenzyme A synthase 1. To ascertain the clinical utility of these findings, we demonstrate that a subset of primary myeloma cells is sensitive to statins and that monitoring dysregulation of the mevalonate pathway may distinguish these cancers. We also show statins are highly effective and well tolerated in an orthotopic model of myeloma using cells harboring this dysregulation. This determinant of sensitivity further provides molecular rationale for the significant therapeutic index of statins on these tumor cells. PMID- 20360470 TI - Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. AB - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by childhood onset of lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, elevated numbers of double-negative T (DNT) cells, and increased risk of lymphoma. Most cases of ALPS are associated with germline mutations of the FAS gene (type Ia), whereas some cases have been noted to have a somatic mutation of FAS primarily in their DNT cells. We sought to determine the proportion of patients with somatic FAS mutations among a group of our ALPS patients with no detectable germline mutation and to further characterize them. We found more than one-third (12 of 31) of the patients tested had somatic FAS mutations, primarily involving the intracellular domain of FAS resulting in loss of normal FAS signaling. Similar to ALPS type Ia patients, the somatic ALPS patients had increased DNT cell numbers and elevated levels of serum vitamin B(12), interleukin-10, and sFAS-L. These data support testing for somatic FAS mutations in DNT cells from ALPS patients with no detectable germline mutation and a similar clinical and laboratory phenotype to that of ALPS type Ia. These findings also highlight the potential role for somatic mutations in the pathogenesis of nonmalignant and/or autoimmune hematologic conditions in adults and children. PMID- 20360471 TI - Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. AB - Bone marrow injury is a major adverse side effect of radiation and chemotherapy. Attempts to limit such damage are warranted, but their success requires a better understanding of how radiation and anticancer drugs harm the bone marrow. Here, we report one pivotal role of the BH3-only protein Puma in the radiosensitivity of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Puma deficiency in mice confers resistance to high-dose radiation in a hematopoietic cell-autonomous manner. Unexpectedly, loss of one Puma allele is sufficient to confer mice radioresistance. Interestingly, null mutation in Puma protects both primitive and differentiated hematopoietic cells from damage caused by low-dose radiation but selectively protects HSCs and HPCs against high-dose radiation, thereby accelerating hematopoietic regeneration. Consistent with these findings, Puma is required for radiation-induced apoptosis in HSCs and HPCs, and Puma is selectively induced by irradiation in primitive hematopoietic cells, and this induction is impaired in Puma-heterozygous cells. Together, our data indicate that selective targeting of p53 downstream apoptotic targets may represent a novel strategy to protecting HSCs and HPCs in patients undergoing intensive cancer radiotherapy and chemotherapy. PMID- 20360472 TI - Syk [sic] of the same old chemotherapy? PMID- 20360473 TI - There's many a CLP on the path to B. PMID- 20360474 TI - The 3 Rs in CLL immune dysfunction. PMID- 20360475 TI - Sugar targets VWF for the chop. PMID- 20360476 TI - Validation of cytogenetic-based risk stratification in primary myelofibrosis. PMID- 20360477 TI - Proposal for a revised classification of systemic mastocytosis. PMID- 20360478 TI - Induction of p53 and up-regulation of the p53 pathway in the human 5q- syndrome. PMID- 20360479 TI - Rapid improvement of life-threatening capillary leak syndrome after stem cell transplantation by bevacizumab. PMID- 20360480 TI - To live or not to live: parenteral nutrition in subjects with isolated gut failure. PMID- 20360481 TI - Inappropriate placement of defibrillator self-adhesive electrode pads with possible fatal outcome. PMID- 20360482 TI - Pilot study of the prevalence, outcomes and detection of occult hypoperfusion in trauma patients. AB - BACKGROUND: Occult hypoperfusion (OH) is defined as hypoperfusion in the presence of normal vital signs. It is associated with increased length of stay (LOS) and increased mortality. OBJECTIVES: To compare four methods of detecting OH in adult major trauma patients at a level 1 trauma centre-base excess (BE), non-invasive cardiac index (CI), shock index (SI) and rate over pressure evaluation (ROPE). METHOD: Patients meeting the Victorian Trauma Registry entrance criteria who presented with normal vital signs were enrolled. CI was obtained half hourly using an USCOM monitor. BE, SI and ROPE were obtained clinically. RESULTS: Sixty four patients were enrolled. Mean injury severity score (ISS) was 19 (SD 11) and mean hospital LOS was 10 days (SD 8). Two patients (3%) died in hospital. Ten patients (16%) had OH detected by CI, seven (11%) by BE, four (6%) by SI and two (3%) by ROPE. There was a significant association between hospital LOS and BE (p<0.005). Agreement between BE and CI in detecting OH was poor to fair, kappa=0.25. CONCLUSION: OH is associated with increased hospital LOS and occurs in up to 16% of patients. BE performed best as a detection method. PMID- 20360483 TI - Achieving a neutral cervical spine position in suspected spinal cord injury in children: analysing the use of a thoracic elevation device for imaging the cervical spine in paediatric patients. AB - BACKGROUND: Paediatric patients with suspected cervical spine injury (CSI) are routinely immobilised on a firm surface using a hard collar, which results in excessive flexion of the cervical spine due to the relatively large size of the occiput. The objective of this study was to determine whether the use of a thoracic elevation device (TED) results in a more neutral cervical spine position and reduces the occurrence of cervical spine hyperflexion. METHODS: A prospective cohort study was conducted at two Emergency Departments (sites A and B) from January 2006 to May 2007. Children < or =10 years of age with suspected CSI requiring cervical imaging were included. Those at site A received a wedge-shaped TED and those at site B did not. x-Rays from both sites were analysed for flexion, extension or neutrality of the cervical spine as defined by the Cobb angle. RESULTS: A total of 76 patients were identified at site A and site B. There were four exclusions at each site for poor quality images. 51 patients in the site A group were found to be in neutral position (71%), compared to 29 patients in the site B group (43%) (p=0.001). One patient (1%) who had a TED was found to be hyperflexed (>10 degrees), whereas 12 (18%) patients at site B were hyperflexed (p=0.001). CONCLUSIONS: The use of a TED appears to produce a greater proportion of neutral cervical spine films in children < or =10 years of age presenting for suspected CSI. PMID- 20360484 TI - Severe chest pain after blunt chest trauma. PMID- 20360485 TI - Intracranial hypotension: an unusual cause of headache in the emergency department. PMID- 20360486 TI - Congenital absence of the posterior arch of the atlas: a benign anomaly? PMID- 20360487 TI - The Hoffa fracture--a fracture not to miss. AB - The Hoffa fracture is a rare unicondylar fracture of the lower femur that occurs in the coronal plane. The nature of the fracture pattern makes it both radiologically and clinically difficult to diagnose. The mechanism of injury is usually high energy, often associated with multiple injuries and so can easily be overlooked. A high degree of suspicion is warranted to avoid missing these fractures which have a propensity to displace if not fixed. This report highlights the clinical presentation and management of a Hoffa fracture in a patient presenting with polytrauma and reviews the current literature. PMID- 20360488 TI - Are routine repeat chest x-rays before leaving the trauma room useful? AB - BACKGROUND: Several guidelines advocate multiple chest x-rays during primary resuscitation of trauma patients. Some local hospital protocols include a repeat x-ray before leaving the trauma resuscitation room (TR). The purpose of this study was to determine the value of routine repeat x-rays. METHODS: One-year data of all radiological imaging in the TR were prospectively collected for all patients presenting to the TR of the hospital. The x-rays were counted and assessed and the findings were classified as either 'new injury detected', 'presence of intervention devices' or 'deterioration of previously detected injury'. RESULTS: A total of 674 patients were included. More than 75% had two x rays. Eight (2.1%) new injuries without clinical relevance were found on the repeat x-ray after an initial normal x-ray. 61 patients (9%) had a repeat x-ray to verify the effect of an intervention or position of devices. In 28 patients (22%) with two abnormal x-rays, newly diagnosed injuries (n=9) or deterioration of known injuries (n=19) were found. In 411 patients (81%) the results of the repeat x-ray had no clinical consequences. CONCLUSION: This study indicates that routine repeat chest x-rays can be omitted in trauma patients whose initial chest x-ray is normal. PMID- 20360489 TI - Do we really need 24-h observation for patients with minimal brain injury and small intracranial bleeding? The Bernese Trauma Unit Protocol. AB - BACKGROUND: Traumatic brain injury is one of the most common reasons for admission to hospital emergency departments. However, optimal diagnosis and treatment protocols remain controversial. The aim of this study is to assess whether a specific group of patients can be discharged from the hospital without 24-h neurological observation. METHODS: Retrospective analysis was performed for 1078 patients with a minor isolated head injury admitted to the authors' Emergency Department for 24-h observation. Exclusion criteria included intracranial bleeds with maximum diameter above 5 mm or multiple (>1) bleeds, a history of inherited coagulopathy or anticoagulant therapy, platelet aggregation inhibitor therapy, intoxication or multiple associated injuries. Furthermore, patients who had no-one to observe them at home or who lived more than 1 h away were excluded from the study. RESULTS: 110 patients presented with an isolated small intracranial bleed (<5 mm) with a Glasgow Coma Scale (GCS) of 13-15. Of these patients, 46% exhibited small intracerebral haematomas, 23% traumatic subarachnoid haematomas, 9% epidural haematomas and 7% subdural haematomas. Nine patients presented with a GCS of 13/15, 30 patients with a GCS 14/15 and 71 patients with a GCS 15/15. 85% of all patients regained GCS 15/15 within 1 h after admission and 15% within 2 h after admission. All patients maintained their GCS 15/15 over the 24-h period. CONCLUSIONS: Standard 24-h observation may not be required for adult patients with single intracranial bleeds with maximum diameter less than 5 mm, without a history of inherited coagulopathy or anticoagulant therapy, platelet aggregation inhibitor therapy, intoxication or multiple associated injuries. The decision for discharging patients may be made from the clinical picture. This might help to spare hospital resources and reduce unnecessary hospitalisations. PMID- 20360490 TI - Portable treatment technologies for urgent care. AB - BACKGROUND: In recent years UK government policy has increased the provision of urgent care in the community. As part of this initiative the emergency ambulance service is gradually changing from an organisation designed to convey patients to hospital to a professional group capable of assessing urgency and delivering the appropriate treatment to the patient. METHODS: This paper explores the portable technology requirements needed to support the new professional roles and draws on examples from ambulance trusts (emergency care practitioner services), primary care (out-of-hours general practitioner services and minor injuries units), and acute trusts (emergency departments) to investigate the workplace layout and clinical activities, including the use of equipment and consumables. It describes the iterative process used to develop the design specification for portable technologies using a qualitative exploratory methodological framework with data collected at stakeholder workshops, responder bag audits, clinical treatment observations and design decision groups. RESULTS: The results are discussed as a three-level technology system for: personal kit; assessment packages (and storage for other clinical treatment packages), a clinical workspace. Future developments are predicted to improve diagnostic and decision-making services through both miniaturisation (eg, portable diagnostic imaging) and improved real-time support (communication systems). CONCLUSION: This study has provided empirical research for portable technology requirements in urgent care. PMID- 20360491 TI - Digital anaesthesia: one injection or two? AB - BACKGROUND: Digital nerve blocks (DNB) are performed frequently in the Emergency Department (ED). The aim of this study was to establish whether single injection subcutaneous digital nerve block (SDNB) is as effective as the traditional (two injection) digital nerve block (TDNB) for digital anaesthesia. METHOD: Single blinded, prospective, randomised-controlled multicentre trial within Hampshire EDs. Patients > or = 16 years attending the ED with fingertip injuries/infections (distal to the distal-interphalangeal joint) requiring a DNB were randomised to SDNB/TDNB groups. Outcome measures were: primary - successful anaesthesia; secondary - patient distress, clinician satisfaction (CS), complications. RESULTS: 76 patients were randomised. (37 received SDNB). At 5 min, more patients in the SDNB group (28/37, 76%) were adequately anaesthetised than in the TDNB group, (22/34, 65%). At 10 min, 33/37 (89%) of the SDNB group compared to 28/34 (82%) of the TDNB group were adequately anaesthetised. The mean (SD) of self reported distress scores for the SDNB group were lower than those reported for the TDNB group, whereas the mean (SD) of CS scores for SDNB were higher than those reported for TDNB. Neither group reported complications from anaesthesia. CONCLUSIONS: SDNB is as effective as TDNB. Outcome measures favoured SDNB, but only CS scores achieved statistical significance. Trial recruitment is much slower than anticipated. However, clinical practice has demonstrated that SDNB works and practice is already changing within the Hampshire region, with some departments adopting SDNB as standard practice. Therefore, the results are being presented now to allow clinicians to make an informed choice. Our results may also contribute to future metanalyses. PMID- 20360493 TI - Urinary bladder hernia: an unusual presentation of abdominal pain. PMID- 20360492 TI - Recovery from sedation with remifentanil and propofol, compared with morphine and midazolam, for reduction in anterior shoulder dislocation. AB - OBJECTIVE: To compare recovery from sedation using remifentanil and propofol with our standard regimen of morphine and midazolam for closed reduction in shoulder dislocation in an ED. METHODS: We randomised 40 patients for closed shoulder reduction to receive either remifentanil and propofol (R&P) (20 patients) or morphine and midazolam (M&M) (20 patients). A suitably trained ED doctor gave the sedation. R&P patients received oxygen from a tight-fitting facemask and Mapleson C circuit to prevent hypocapnia and thus reduce the risk of apnoea. Shoulder reduction was performed by another doctor with an ED nurse also present. We noted recovery times, pain and sedation scores, operative conditions, additional medication and adverse events. RESULTS: All patients given remifentanil and propofol had recovered within 30 min in contrast to the morphine and midazolam group where 17 of 20 patients had recovered after 60 min, the remainder requiring a total of 90 min. Median recovery times were 15 min (95% CI 15 to 20) for the remifentanil and propofol group, and 45 min (95% CI 29 to 48) for the morphine and midazolam group. Reduction conditions and scores for pain/distress did not differ between the groups. Seven patients required additional sedation (four R&P, three M&M) to enable shoulder reduction. Five patients (three R&P, two M&M) had received analgesia prior to the procedure from the ambulance service (one R&P, one M&M) and ED (two R&P). Two patients given morphine and midazolam required flumazenil to counter oversedation. CONCLUSIONS: Remifentanil and propofol reduces patient recovery time and provides equivalent operating conditions compared with morphine and midazolam for the reduction of anterior glenohumeral dislocation. PMID- 20360494 TI - Unexpected failure of central venous catheterisation for resuscitation. PMID- 20360495 TI - Fatal nefopam overdose. AB - Nefopam hydrochloride (Acupan) is a potent non-opioid analgesic widely used for the relief of moderate to severe postoperative pain. The drug is generally well tolerated, but it has a broad spectrum of side effects including tachycardia, sweating, nausea, seizures and hallucinations. When taken in overdose, nefopam has been reported to cause cardiac conduction abnormalities, cerebral oedema, fever and renal failure. The case is presented of a previously healthy 19-year old man who presented to the emergency department in cardiac arrest following intentional nefopam overdose. It is only the fourth reported case of fatal nefopam overdose in the literature. PMID- 20360496 TI - An unusual presentation of a leaking abdominal aortic aneurysm. PMID- 20360497 TI - Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults. AB - INTRODUCTION: Bacterial meningitis is a medical emergency, the outcome of which is improved by prompt antibiotic treatment. For patients with suspected meningitis and no features of severe disease, the British Infection Society recommends immediate lumbar puncture (LP) before antibiotics, to maximise the chance of a positive cerebrospinal (CSF) culture. In such patients, CT scanning before LP is not needed. METHODS: The case notes of adults with meningitis admitted to a large district general hospital over 3 years were reviewed. Patients were classified as Likely Bacterial Meningitis or Likely Viral Meningitis based on their CSF and peripheral blood results using the Meningitest Criteria, with microbiological and virological confirmation. RESULTS: Of 92 patients studied, 24 had Likely Bacterial Meningitis, including 16 with microbiologically confirmed disease (none had PCR tests for bacteria). Sixty eight had Likely Viral Meningitis, four of whom had viral PCR, including one with herpes simplex virus. No patient had an LP before antibiotics. CSF culture was positive for eight (73%) of the 11 patients who had an LP up to 4 h after starting antibiotics, compared with eight (11%) of 71 patients with a later LP (p<0.001). None of the 34 LPs performed more than 8 h after antibiotics was culture-positive. For 62 (67%) of the 92 patients, the delay was due to a CT scan, although only 20 of these patients had a contraindication to an immediate LP. CONCLUSIONS: Too many patients with acute bacterial meningitis are being sent for unnecessary CT scans, causing delays in the LP, and reducing the chances of a positive CSF culture after starting antibiotics. However, even if antibiotics have been started, an LP within 4 h is still likely to be positive. Molecular tests for diagnosis should also be requested. PMID- 20360498 TI - Ketamine improves nasogastric tube insertion. AB - OBJECTIVES: Nasogastric (NG) intubation is one of the most common procedures performed in the emergency department (ED) and other hospital settings. The aim of this study was to compare the level of pain during NG tube insertion in groups receiving local ketamine plus water-soluble lubricating gel and water-soluble lubricating gel alone (the latter is the common practice in our hospital). It was hypothesised that ketamine has local anaesthetic effects in reducing the pain of NG tube insertion in the ED. METHODS: This prospective double-blind randomised clinical trial was performed on alert haemodynamically stable subjects aged >18 years who required NG tube placement for diagnostic or therapeutic purposes in the ED of a teaching hospital during January and June 2008. The subjects were divided into two groups using randomised allocation software. The ketamine group received intranasal ketamine, while an equivalent volume of sterile water was instilled into the nasal cavity in the control group. The same amount of lubricating gel was used in both groups. The pain of NG tube placement was measured using a standard 100 mm visual analogue scale (VAS). The physician was asked to evaluate the difficulty of the procedure using a 5-point Likert scale. RESULTS: Seventy-two subjects were enrolled in the study (36 subjects in each group). There was a significant difference between the pain score of the ketamine and control groups (19.03+/-3.56 vs 33.33+/-5.31), while the difficulty score was not statistically different between the two groups (2.39+/-1.25 vs 2.78+/-1.56). CONCLUSION: Intranasal ketamine is an effective agent in reducing pain during NG tube insertion among patients without serious underlying illness. PMID- 20360500 TI - A comparison of the long gamma nail with the sliding hip screw for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur: a prospective randomized trial. AB - BACKGROUND: Controversy exists with regard to whether to treat AO/OTA 31-A2 fractures of the proximal part of the femur with an intramedullary device or an extramedullary device. A prospective, randomized, controlled trial was performed to compare the outcome of treatment of these unstable fractures of the proximal part of the femur with either a sliding hip screw or a long gamma nail. METHODS: Two hundred and ten patients presenting with an AO/OTA 31-A2 fracture of the proximal part of the femur were randomized, at the time of admission, to fixation with use of either a long gamma nail or a sliding hip screw. The primary outcome measure was reoperation within the first postoperative year. Secondary measures included mortality, length of hospital stay, transfusion rate, change in mobility and residence, and quality of life as measured with the EuroQol 5D outcome score. RESULTS: There was no significant difference between the reoperation rates for the two groups. In total, five patients (three from the long-gamma-nail group and two from the sliding-hip-screw group) underwent revision surgery because of cut out. Tip-apex distance was found to correlate with the implant cut-out rate. There was no significant difference between the two groups in terms of the EuroQol 5D outcome scores, the mortality rates after correction for the mini mental score, or any of the secondary outcome measures. CONCLUSIONS: When compared with the long gamma nail, the sliding hip screw should remain the gold standard for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur because it is associated with similar outcomes with less expense. PMID- 20360501 TI - Ninety-day mortality after intertrochanteric hip fracture: does provider volume matter? AB - BACKGROUND: Research on the relationship between orthopaedic volume and outcomes has focused almost exclusively on elective arthroplasty procedures. Geriatric patients who have sustained an intertrochanteric hip fracture are older and have a heavier comorbidity burden in comparison with patients undergoing elective arthroplasty; therefore, any advantage of provider volume in terms of mortality could be overwhelmed by the severity of the hip fracture condition itself. This study examined the association between surgeon and hospital volumes of procedures performed for the treatment of intertrochanteric hip fractures in Medicare beneficiaries and inpatient through ninety-day postoperative mortality. METHODS: The Medicare 100% files of hospital and physician claims plus the beneficiary enrollment files for 2000 through 2002 identified beneficiaries who were sixty five years of age or older and who underwent inpatient surgery for the treatment of an intertrochanteric hip fracture with internal fixation. Provider volumes of intertrochanteric hip fracture cases were calculated with use of unique surgeon and hospital provider numbers in the claims. Fixed effects regression analysis using generalized estimating equations was used to model the association between hospital and surgeon intertrochanteric hip fracture volume and inpatient through ninety-day mortality, controlling for age, sex, race, Charlson comorbidity score, subtrochanteric fracture, prefracture nursing home residence, Medicaid administered assistance, surgical device, and year. The unadjusted inpatient, thirty, sixty, and ninety-day mortality rates and adjusted relative risks are reported. RESULTS: Between March 1, 2000, and December 31, 2002, 192,365 claims met inclusion criteria and matched with provider information. The unadjusted inpatient, thirty-day, sixty-day, and ninety-day mortality rates were 2.91%, 7.92%, 12.34%, and 15.19%, respectively. Patients managed at lower-volume hospitals had significantly higher (10% to 20%) adjusted risks of inpatient mortality than those managed at the highest-volume hospitals. By sixty days postoperatively, the increased mortality risk persisted only among patients managed at the lowest-volume hospitals (six cases per year or fewer). Patients who were managed by surgeons who treated an average of two or three cases per year had the highest mortality risks when compared with patients managed by the highest-volume surgeons. CONCLUSIONS: Only the highest-volume hospitals showed an inpatient mortality benefit for Medicare patients with intertrochanteric hip fractures. Unlike the situation with elective arthroplasty procedures, our findings do not indicate a need to direct patients with routine hip fractures exclusively to high-volume centers, although the higher mortality rates found in the lowest-volume hospitals warrant further investigation. PMID- 20360502 TI - Use of medical comorbidities to predict complications after hip fracture surgery in the elderly. AB - BACKGROUND: Comorbidities before and complications following hip fracture surgery can impact the return of function. We hypothesized that the American Society of Anesthesiologists (ASA) classification of medical comorbidities is a useful surrogate variable for the patient's general medical condition and would be a strong predictor of perioperative medical complications following hip fracture surgery. METHODS: A retrospective review of the cases of 197 elderly patients who had undergone operative management of a hip fracture was performed. The ASA class, data regarding perioperative medical and surgical complications, and demographic data were obtained. Medical complications were defined as those requiring intervention by an internist or medical specialist. Differences in complication rates among the ASA classes were determined. RESULTS: Medical complications were more common in patients in ASA class 3 (p < 0.001) and those in class 4 (p = 0.001) than in those in class 2. Patients in ASA class 3 had a 3.78 times greater chance of having a medical complication than did those in class 2 (p < 0.001). Patients in ASA class 4 had a 7.39 times greater chance of having medical complications than did those in class 2 (p = 0.001). No significant relationship was identified between the ASA class and surgical complications. CONCLUSIONS: The ASA class is strongly associated with medical problems in the perioperative period following hip fracture surgery in the elderly. Patients identified as being at higher risk (in ASA class 3 or 4) preoperatively should be closely managed medically so that perioperative medical complications can be managed and evolving medical issues can be addressed in a timely fashion. PMID- 20360503 TI - Ergometer cycling after hip or knee replacement surgery: a randomized controlled trial. AB - BACKGROUND: The optimal treatment strategy following primary total hip or knee replacement remains unknown. The purpose of this study was to evaluate the effect of ergometer cycling after hip or knee replacement surgery on health-related quality of life and patient satisfaction. METHODS: Three hundred and sixty-two patients were randomly assigned to either perform or not perform ergometer cycling beginning two weeks after total hip or knee replacement. The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at three, six, twelve, and twenty-four months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. RESULTS: The baseline characteristics of the two groups were similar. After the hip arthroplasties, all of the outcome parameters were superior in the ergometer cycling group at all follow-up intervals, and the primary outcome, physical function as measured with the WOMAC, was significantly better at three months (21.6 compared with 16.4 points, effect size = 0.33, p = 0.046) and twenty-four months (14.7 compared with 9.0 points, effect size = 0.37, p = 0.019). After the hip arthroplasties, a higher percentage of the ergometer cycling group was "very satisfied" at all follow-up intervals (for example, 92% compared with 80% at three months; p = 0.027). The significant differences in the primary outcome exceeded the absolute minimal clinically important improvement threshold by a factor of 2.0. No significant differences between the study groups were seen after the knee arthroplasties. CONCLUSIONS: Ergometer cycling after total hip arthroplasty is an effective means of achieving significant and clinically important improvement in patients' early and late health-related quality of life and satisfaction. However, this study does not support the use of ergometer cycling after knee arthroplasty. PMID- 20360504 TI - Maintenance of hardware after early postoperative infection following fracture internal fixation. AB - BACKGROUND: The development of a deep wound infection in the presence of hardware after open reduction and internal fixation presents a clinical dilemma, and there is scant literature to aid in decision-making. The purpose of the present study was to determine the prevalence of osseous union with maintenance of hardware after the development of postoperative infection within six weeks after internal fixation of a fracture. METHODS: The present study included 121 patients from three level-I trauma centers, retrospectively identified from billing and trauma registries, in whom 123 postoperative wound infections with positive intraoperative cultures had developed within six weeks after internal fixation of acute fractures. The incidence of fracture union without hardware removal was calculated, and the parameters that predicted success or failure were evaluated. RESULTS: Eighty-six patients (eighty-seven fractures; 71%) had fracture union with operative debridement, retention of hardware, and culture-specific antibiotic treatment and suppression. Predictors of treatment failure were open fracture (p = 0.03) and the presence of an intramedullary nail (p = 0.01). Several variables were not significant but trended toward an association with failure, including smoking, infection with Pseudomonas species, and involvement of the femur, tibia, ankle, or foot. CONCLUSIONS: Deep infection after internal fixation of a fracture can be treated successfully with operative debridement, antibiotic suppression, and retention of hardware until fracture union occurs. These results may be improved by patient selection based on certain risk factors and the specific bacteria and implants involved. PMID- 20360506 TI - Renal clearance of cobalt in relation to the use of metal-on-metal bearings in hip arthroplasty. AB - BACKGROUND: A concern regarding the use of metal-on-metal bearings in hip arthroplasty has been that the high levels of metal ions that are released overwhelm the renal threshold for metal excretion, leading to systemic buildup of metals. The purpose of this investigation was to determine if the physiological renal capacity for cobalt clearance and cobalt concentrating efficiency is overwhelmed by the elevation in metal ion levels seen in patients with metal-on metal-bearing hip devices. METHODS: Concurrent specimens of urine and plasma were obtained from a group of 461 patients (346 men and 115 women) at various intervals after either a unilateral (296) or a bilateral (130) metal-on-metal hip arthroplasty or preoperatively (thirty-five patients; the control specimens). Metal ion analyses were performed with high-resolution inductively coupled mass spectrometry. Renal efficiency was measured as the ratio of urine cobalt concentration to plasma cobalt concentration. Cobalt clearance was calculated by dividing the urine cobalt output in twenty-four hours by the plasma cobalt concentration. Dividing the quotient by 1440 adjusts it to clearance per minute. RESULTS: The median renal efficiency was found to be 0.9 in the analysis of the preoperative specimens, indicating that there was renal conservation of cobalt. In patients with metal-on-metal bearings, the median renal efficiency was 3.2, indicating that, as a result of cobalt excretion, the cobalt concentration in urine was threefold higher than the concentration in plasma. Linear regression analysis showed that renal efficiency progressively increased at a rate of 9% for every microg/24 hr increase in cobalt release. Cobalt clearance showed a similar trend, increasing from 1.3 mL/min in the preoperative group to 3.7 mL/min in the follow-up group. In the follow-up group, renal cobalt clearance progressively increased from 1.9 to 7.1 mL/min with increasing daily cobalt output, which indicates that with increasing in vivo metal ion release there was a progressive increase in the rate at which the kidneys cleared the plasma of cobalt. CONCLUSIONS: In subjects with no prosthetic device, the kidneys tend to conserve cobalt in the body. We found that, in patients with a metal-on-metal hip prosthesis, there is a progressive increase in cobalt clearance with increasing in vivo wear at the levels of cobalt release expected in patients with an array of metal-on-metal-bearing total joint arthroplasties. We found no threshold beyond which renal capacity to excrete these ions is overwhelmed. PMID- 20360505 TI - Relationship of tear size and location to fatty degeneration of the rotator cuff. AB - BACKGROUND: Fatty degeneration of the rotator cuff muscles may have detrimental effects on both anatomical and functional outcomes following shoulder surgery. The purpose of this study was to investigate the relationship between tear geometry and muscle fatty degeneration in shoulders with a deficient rotator cuff. METHODS: Ultrasonograms of both shoulders of 262 patients were reviewed to assess the type of rotator cuff tear and fatty degeneration in the supraspinatus and infraspinatus muscles. The 251 shoulders with a full-thickness tear underwent further evaluation for tear size and location. The relationship of tear size and location to fatty degeneration of the supraspinatus and infraspinatus muscles was investigated with use of statistical comparisons and regression models. RESULTS: Fatty degeneration was found almost exclusively in shoulders with a full thickness rotator cuff tear. Of the 251 shoulders with a full-thickness tear, eighty-seven (34.7%) had fatty degeneration in either the supraspinatus or infraspinatus, or both. Eighty-two (32.7%) of the 251 full-thickness tears had a distance of 0 mm between the biceps tendon and anterior margin of the tear. Ninety percent of the full-thickness tears with fatty degeneration in both muscles had a distance of 0 mm posterior from the biceps, whereas only 9% of those without fatty degeneration had a distance of 0 mm. Tears with fatty degeneration had significantly greater width and length than those without fatty degeneration (p < 0.0001). Tears with fatty degeneration had a significantly shorter distance posterior from the biceps than those without fatty degeneration (p < 0.0001). The distance posterior from the biceps was found to be the most important predictor for supraspinatus fatty degeneration, whereas tear width and length were found to be the most important predictors for infraspinatus fatty degeneration. CONCLUSIONS: Fatty degeneration of the rotator cuff muscles is closely associated with tear size and location. The finding of this study suggests that the integrity of the anterior supraspinatus tendon is important to the development of fatty degeneration. Patients with full-thickness tears that extend through this area may benefit from earlier surgical intervention if fatty degeneration has not already occurred. Additionally, the findings suggest the importance of secure fixation and healing of the anterior aspect of the supraspinatus with surgical repair. PMID- 20360507 TI - Shock wave therapy compared with intramedullary screw fixation for nonunion of proximal fifth metatarsal metaphyseal-diaphyseal fractures. AB - BACKGROUND: The current "gold standard" for treatment of chronic fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal is intramedullary screw fixation. Complications with this procedure, however, are not uncommon. Shock wave therapy can be an effective treatment for fracture nonunions. The purpose of this study was to evaluate the safety and efficacy of shock wave therapy as a treatment of these nonunions. METHODS: Twenty-three patients with a fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal received high-energy shock wave therapy (2000 to 4000 shocks; energy flux density per pulse, 0.35 mJ/mm(2)), and twenty other patients with the same type of fracture nonunion were treated with intramedullary screw fixation. The numbers of fractures that were healed at three and six months after treatment in each group were determined, and treatment complications were recorded. RESULTS: Twenty of the twenty-three nonunions in the shock wave group and eighteen of the twenty nonunions in the screw fixation group were healed at three months after treatment. One of the three nonunions that had not healed by three months in the shock wave group was healed by six months. There was one complication in the shock wave group (post-treatment petechiae) and eleven complications in the screw-fixation group (one refracture, one case of cellulitis, and nine cases of symptomatic hardware). CONCLUSIONS: Both intramedullary screw fixation and shock wave therapy are effective treatments for fracture nonunion in the metaphyseal-diaphyseal region of the fifth metatarsal. Screw fixation is more often associated with complications that frequently result in additional surgery. PMID- 20360508 TI - Treatment of unicameral bone cyst: a comparative study of selected techniques. AB - BACKGROUND: There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. METHODS: From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. RESULTS: The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 +/- 2.3 months compared with 23.4 +/- 14.9, 12.2 +/- 8.5, and 6.6 +/- 4.3 months in Groups 1, 2, and 3, respectively. CONCLUSIONS: This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts. PMID- 20360509 TI - Correlation between muscle oxygenation and compartment pressures in acute compartment syndrome of the leg. AB - BACKGROUND: Near-infrared spectroscopy estimates soft-tissue oxygenation approximately 2 to 3 cm below the skin. The purpose of the present study was to evaluate muscle oxygenation in the setting of an acute compartment syndrome of the leg and to determine if near-infrared spectroscopy is capable of detecting perfusion deficits. METHODS: Fourteen patients with unilateral lower extremity trauma were enrolled after the diagnosis of an acute compartment syndrome was made clinically and confirmed with intracompartmental pressure measurements. Lower extremity muscle compartments were evaluated with near-infrared spectroscopy, and near-infrared spectroscopy values of the uninjured, contralateral leg of each patient were used as internal reference values. The compartment perfusion gradient was calculated as the diastolic blood pressure minus the intracompartmental pressure. RESULTS: Intracompartmental pressures ranged from 21 to 176 mm Hg (mean, 79 mm Hg) and exceeded 30 mm Hg in all compartments but two (both in the same patient). Thirty-eight compartments had a perfusion gradient of < or = 10 mm Hg (indicating ischemia). Among ischemic compartments, near-infrared spectroscopy values in the anterior, lateral, deep posterior, and superficial posterior compartments of the injured limbs were decreased by an average 10.1%, 10.1%, 9.4%, and 16.3% in comparison with the corresponding compartments of the uninjured leg. Differences in near-infrared spectroscopy values (the near-infrared spectroscopy value for the injured leg minus the near-infrared spectroscopy value for the uninjured leg) were positively correlated with compartment perfusion gradient within each compartment (r = 0.82, 0.65, 0.67, and 0.62, for the anterior, lateral, deep posterior, and superficial posterior compartments, respectively; p < 0.05 for all). CONCLUSIONS: Normalized near-infrared spectroscopy values decrease significantly with decreasing lower limb perfusion pressures. Near-infrared spectroscopy may be capable of differentiating between injured patients with and without an acute compartment syndrome. PMID- 20360510 TI - Effect of tibial drill angles on bone tunnel aperture during anterior cruciate ligament reconstruction. AB - BACKGROUND: Anatomic reconstruction of the anterior cruciate ligament has received greater attention as patient outcome assessment has become increasingly sophisticated. A goal during anatomic reconstruction should be the creation of a tibial tunnel aperture that is similar in size and orientation to the native anterior cruciate ligament insertion. Aperture morphology depends primarily on three factors: (1) drill-bit diameter, (2) the angle at which the tunnel intersects the tibial plateau (drill-guide angle), and (3) the tibial tunnel orientation in the transverse plane (transverse drill angle). We evaluated the influence of the aforementioned factors on tibial bone-tunnel aperture size and orientation. METHODS: With use of various drill-bit diameters at different drill guide angles, tunnel aperture areas were calculated on the basis of an elliptical shape. The change in tunnel aperture orientation within the transverse plane (along the tibial plateau surface) was quantified by calculating the change in anteroposterior and mediolateral lengths of the aperture. RESULTS: Use of a 9-mm drill-bit at a 45 degrees drill-guide angle created a 90-mm(2) bone-tunnel aperture area. Decreasing the drill-guide angle from 65 degrees to 30 degrees resulted in an increase in area of 81%. An aperture oriented 45 degrees relative to the orientation of the native insertion of the anterior cruciate ligament in the transverse plane fell short of the anatomic anteroposterior distance by 2.3 mm and exceeded the mediolateral distance by 1.4 mm on the basis of a 9-mm drill bit at a drill-guide angle of 45 degrees. CONCLUSIONS: During anterior cruciate ligament reconstruction, the drill-bit diameter, sagittal drill angle, and transverse drill angle can all affect tibial tunnel aperture size and orientation. An improperly sized and oriented tunnel aperture may increase the risk of damaging surrounding structures. An optimal combination of these parameters should be chosen during anatomic reconstruction of the anterior cruciate ligament. PMID- 20360511 TI - Has the rate of extensive surgery to treat idiopathic clubfoot declined in the United States? AB - BACKGROUND: In the late 1990s, renewed interest emerged in less invasive treatment options, most notably the Ponseti method, to correct idiopathic clubfoot deformity. Recently, reports from several centers have demonstrated that such minimally invasive techniques may be used reliably to correct this complex deformity. The present study sought to determine whether the rate of extensive surgical releases to treat idiopathic clubfoot in the United States has decreased. METHODS: We used data from the Centers for Disease Control and Prevention and the Nationwide Inpatient Sample to determine the number of live births, the number of patients diagnosed with clubfoot, and the number of extensive surgical releases that were performed each year from 1996 to 2006. The trends over time were evaluated with use of regression analysis, and changes in frequency were analyzed with use of time series analysis. The percentage of clubfeet that were treated with surgery in each year was calculated by dividing the number of surgical release procedures by the number of clubfoot diagnoses. RESULTS: Between 1996 and 2006, the estimated number of patients under six months of age diagnosed with clubfoot remained fairly constant, averaging 2140 infants per year. The linear equation estimated a slight decrease of approximately thirty one infants with clubfoot per year (R(2) = 0.51, p < 0.05). In contrast, in the same decade, the estimated number of surgical releases performed in patients less than twelve months of age decreased substantially, from 1641 releases in 1996 to 230 releases in 2006. The linear equation estimated a decrease of approximately 157 surgical releases per year (R(2) = 0.83, p < 0.05). The trend analysis indicated that the percentage of clubfeet treated with surgical release generally decreased over time at a rate of 6.7% per year, decreasing from just over 70% in 1996 to just over 10% in 2006 (R(2) = 0.81, p < 0.05). CONCLUSIONS: In the United States between 1996 and 2006, the rate of extensive surgery to treat idiopathic clubfoot in patients less than twelve months old decreased substantially. This trend is likely due to an increased use of less invasive techniques, such as the Ponseti method, which a growing body of evidence has shown to be a viable treatment option for clubfoot. PMID- 20360512 TI - Isolated subtalar dislocation. AB - BACKGROUND: Little attention has been devoted to subtalar dislocations without an associated bone injury in the literature to date. The aim of this study was to assess the functional and subjective results of a cohort of patients with this injury. METHODS: A total of ninety-seven patients with a subtalar dislocation were treated at two major university trauma centers from January 1994 to March 2007. Computed tomographic scans indicated a subtalar dislocation without associated bone injury in twenty-three of these patients. Clinical and radiographic examinations were performed on all twenty-three patients at an average of 58.3 months after the completion of treatment. The postoperative clinical examination was supplemented by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and the degree of arthritis was assessed radiographically. RESULTS: The average score on the AOFAS ankle-hindfoot scale score was 82.3 points. Twenty-one patients achieved a good result, and two patients had a satisfactory result. The range of motion of the subtalar joint was an average of 41.3 degrees. No difference between the results of the medial and lateral subtalar dislocations was observed. Only six patients had minor radiographic changes. CONCLUSIONS: The intermediate-term results for a subtalar dislocation without an associated osseous injury are good, and the direction of the dislocation does not appear to make a difference with regard to clinical or radiographic outcome. PMID- 20360513 TI - Acetabular retroversion in developmental dysplasia of the hip. AB - BACKGROUND: Patients with developmental dysplasia of the hip are prone to the development of degenerative changes in the affected hip. The aim of this study was to evaluate the prevalence, morphological features, and clinical relevance of acetabular retroversion in these patients. METHODS: We investigated the version and morphological features of the acetabulum using pelvic radiographs and computed tomography images of ninety-six hips in fifty-nine patients with developmental dysplasia of the hip. A diagnosis of acetabular retroversion was based on the presence of a positive cross-over sign on the pelvic radiograph. Using computed tomography images, we determined the acetabular anteversion angle at various levels in the axial plane. The acetabular sector angle served as an indicator of acetabular coverage of the femoral head. We evaluated the association between acetabular version and the patient's age at the onset of pain. Fifty normal hips were examined as controls. RESULTS: We observed acetabular retroversion in 18% (seventeen) of the ninety-six hips in the patients with developmental dysplasia of the hip. The mean acetabular anteversion angle in the hips with acetabular retroversion was significantly smaller, at all levels, than that in the hips with acetabular anteversion; this tendency was more evident at proximal levels. There was significantly less posterior and posterosuperior coverage in the hips with acetabular retroversion than in those with acetabular anteversion, but superior acetabular coverage did not differ between the groups. Multivariate analysis showed that the onset of pain occurred at a significantly earlier age in patients with acetabular retroversion (27.9 years) than in those with acetabular anteversion (40.5 years), regardless of the severity of the dysplasia (p = 0.003). CONCLUSIONS: In patients with developmental dysplasia of the hip, acetabular retroversion results from relatively deficient coverage by the posterior portion of the acetabulum. Developmental dysplasia with acetabular retroversion is associated with an earlier onset of pain than is developmental dysplasia with anteversion, suggesting a correlation between deficiency of the posterior acetabular wall and the earlier onset of pain. PMID- 20360514 TI - Prospective longitudinal evaluation of elbow motion following pediatric supracondylar humeral fractures. AB - BACKGROUND: Temporary elbow stiffness after the treatment of a supracondylar humeral fracture in a child is often a concern of parents. However, little attention has been devoted to documenting, longitudinally, the time required for motion recovery. The purpose of the present study was to provide a prospective, longitudinal evaluation of elbow motion in a large population of pediatric patients undergoing treatment of a supracondylar humeral fracture. METHODS: We prospectively examined 373 patients (375 fractures) who presented to our urgent care center between March 1, 2007, and September 30, 2008. On the basis of a standard protocol, patients were managed with either casting or surgery, depending on the severity of the injury, and then were followed for a minimum of seven weeks. Values of elbow flexion and extension were recorded, and the relative arc of motion was calculated as a percentage of the motion of the contralateral elbow. RESULTS: In general, following a supracondylar humeral fracture, the greatest increases in flexion, extension, and the absolute and relative arcs of motion are observed within the first month after cast removal, with a progressive improvement for up to forty-eight weeks after the injury. Age had a significant effect on the recovery of elbow motion, with patients older than five years of age demonstrating a 3% to 9% lower relative arc of motion at the follow-up points in comparison with younger patients. Similarly, patients with more-severe fractures requiring surgical treatment demonstrated a decrease in relative elbow motion of 10% (with respect to the contralateral side) at the time of cast removal in comparison with those who were managed nonoperatively. CONCLUSIONS: The present study demonstrates that an initial rapid recovery in elbow motion can be expected after a supracondylar humeral fracture in a child, followed by a progressive improvement for up to one year after the injury. This motion recovery is slower in older patients and in those with more severe injuries. PMID- 20360515 TI - Plantar flexion influences radiographic measurements of the ankle mortise. AB - BACKGROUND: The treatment of ankle fractures often depends on the integrity of the deltoid ligament. Diagnosis of a deltoid ligament tear depends on the measurement of the medial clear space. We sought to evaluate the impact of ankle plantar flexion on the medial clear space. METHODS: Mortise radiographs were made for twenty-five healthy volunteers, with the ankle in four positions of plantar flexion (0 degrees, 15 degrees, 30 degrees, and 45 degrees). Four observers measured the medial clear space and the superior clear space on each radiograph. The mean medial clear space at 0 degrees was defined as the control, and the deviation of the medial clear space from the control value was calculated at 15 degrees, 30 degrees, and 45 degrees of plantar flexion. The ratio of the medial clear space to the superior clear space was determined on all radiographs, and ratios that were false-positive for a deltoid ligament injury were identified. RESULTS: Fourteen male and eleven female volunteers were evaluated. The average increase in the medial clear space when ankle plantar flexion was increased from 0 degrees to 45 degrees was 0.38 mm (95% confidence interval, 0.18 to 0.58 mm). This increase was significant (p = 0.005). The average increase in the medial clear space was 0.04 mm when ankle plantar flexion was increased from 0 degrees to 15 degrees and 0.22 mm when it was increased from 0 degrees to 30 degrees. Neither of these changes was significant (p = 0.99 and 0.20). The prevalence of false-positive findings of deltoid injury based on the ratio of the medial clear space to the superior clear space increased as ankle plantar flexion increased, but this increase did not reach significance in our study group (p = 0.18). CONCLUSIONS: Plantar flexion of the ankle produces changes in radiographic measurements of the medial clear space. The potential for false-positive findings of deltoid disruption increases with increasing ankle plantar flexion. PMID- 20360516 TI - Glenohumeral contact kinematics in patients after total shoulder arthroplasty. AB - BACKGROUND: Knowledge of in vivo glenohumeral joint contact mechanics after total shoulder arthroplasty may provide insight for the improvement of patient function, implant longevity, and surgical technique. The objective of this study was to determine the in vivo glenohumeral joint contact locations in patients after total shoulder arthroplasty. We hypothesized that the glenohumeral joint articular contact would be centered on the glenoid surface because of the ball-in socket geometric features of the implants. METHODS: Dual-plane fluoroscopic images and computer-aided design models were used to quantify patient-specific glenohumeral articular contact in thirteen shoulders following total shoulder arthroplasty. The reconstructed shoulder was imaged at arm positions of 0 degrees, 45 degrees, and 90 degrees of abduction (in the coronal plane) and neutral rotation and at 90 degrees of abduction with maximum internal and external rotation. The patients were individually investigated, and their glenohumeral joint contact centroids were reported with use of contact frequency. RESULTS: In all positions, the glenohumeral joint contact centroids were not found at the center of the glenoid surface but at an average distance (and standard deviation) of 11.0 +/- 4.3 mm from the glenoid center. Forty (62%) of the sixty-five total contact occurrences were found on the superior-posterior quadrant of the glenoid surface. The position of 0 degrees of abduction in neutral rotation exhibited the greatest variation of quadrant contact location; however, no contact was found on the superior-anterior quadrant of the glenoid surface in this position. CONCLUSIONS: In vivo, glenohumeral joint contact after total shoulder arthroplasty is not centered on the glenoid surface, suggesting that kinematics after shoulder arthroplasty may not be governed by ball-in-socket mechanics as traditionally thought. Although contact locations as a function of arm position vary among patients, the superior-posterior quadrant seems to experience the most articular contact in the shoulder positions tested. PMID- 20360517 TI - Reliability of clinical findings and magnetic resonance imaging for the diagnosis of chondromalacia patellae. AB - BACKGROUND: This diagnostic study was performed to determine the correlation between anterior knee pain and chondromalacia patellae and to define the reliability of magnetic resonance imaging for the diagnosis of chondromalacia patellae. METHODS: Fifty-six young adults (median age, 19.5 years) with anterior knee pain had magnetic resonance imaging of the knee followed by arthroscopy. The patellar chondral lesions identified by magnetic resonance imaging were compared with the arthroscopic findings. RESULTS: Arthroscopy confirmed the presence of chondromalacia patellae in twenty-five (45%) of the fifty-six knees, a synovial plica in twenty-five knees, a meniscal tear in four knees, and a femorotibial chondral lesion in four knees; normal anatomy was seen in six knees. No association was found between the severity of the chondromalacia patellae seen at arthroscopy and the clinical symptoms of anterior knee pain syndrome (p = 0.83). The positive predictive value for the ability of 1.0-T magnetic resonance imaging to detect chondromalacia patellae was 75% (95% confidence interval, 53% to 89%), the negative predictive value was 72% (95% confidence interval, 56% to 84%), the sensitivity was 60% (95% confidence interval, 41% to 77%), the specificity was 84% (95% confidence interval, 67% to 93%), and the diagnostic accuracy was 73% (95% confidence interval, 60% to 83%). The sensitivity was 13% (95% confidence interval, 2% to 49%) for grade-I lesions and 83% (95% confidence interval, 59% to 94%) for grade-II, III, or IV lesions. CONCLUSIONS: Chondromalacia patellae cannot be diagnosed on the basis of symptoms or with current physical examination methods. The present study demonstrated no correlation between the severity of chondromalacia patellae and the clinical symptoms of anterior knee pain syndrome. Thus, symptoms of anterior knee pain syndrome should not be used as an indication for knee arthroscopy. The sensitivity of 1.0-T magnetic resonance imaging was low for grade-I lesions but considerably higher for more severe (grade-II, III, or IV) lesions. Magnetic resonance imaging may be considered an accurate diagnostic tool for identification of more severe cases of chondromalacia patellae. PMID- 20360518 TI - Structural changes in muscle and glenohumeral joint deformity in neonatal brachial plexus palsy. AB - BACKGROUND: Internal rotation contracture of the shoulder is common in children with neonatal brachial plexus palsy. A long-standing contracture may cause osseous deformities in the developing shoulder. The purpose of the study was to evaluate the relationship between osseous deformities of the glenohumeral joint and structural differences due to muscle denervation in the rotator cuff muscles. METHODS: One hundred and two children with residual neonatal brachial plexus palsy underwent magnetic resonance imaging of both shoulders. The glenoid version and posterior, medial, and superior subluxation of the humeral head were measured. The shapes of the glenoid and the humeral head were categorized, and the infraspinatus, supraspinatus, subscapularis, and deltoid muscles were scored as being normal, atrophic, or atrophic with fatty degeneration. RESULTS: Muscle degeneration was most prominent in the subscapularis muscle. Glenoid version correlated with the structural differences in the subscapularis muscle. Posterior subluxation of the humeral head and the shape of the glenoid correlated with all abnormal rotator cuff muscles. Superior humeral subluxation correlated only with changes in the supraspinatus muscle. Medialization and the shape of the humeral head were not associated with atrophic changes of the rotator cuff. Regeneration of the rotator cuff muscles was not significantly different in patients with a C5 C6 (C7) or a complete brachial plexus lesion. However, the changes in glenoid version, the degree of posterior humeral subluxation, and the degree of medial humeral subluxation were significantly more severe in patients with a C5-C6 (C7) lesion compared with those in patients with a complete lesion of the brachial plexus. CONCLUSIONS: Structural differences in the rotator cuff muscles alter the direction of the humeral head forces on the developing glenoid fossa and can lead to osseous deformities. Glenohumeral deformities are significantly greater with a C5-C6 (C7) lesion than with a complete brachial plexus lesion in which the large internal rotators are also affected. Reducing the muscular imbalance that occurs with a C5-C6 (C7) lesion could diminish glenohumeral joint incongruency and may improve the outcome of subsequent soft-tissue release or tendon transfer surgery. PMID- 20360519 TI - Quantitative assessment of the vascularity of the proximal part of the humerus. AB - BACKGROUND: The current consensus in the literature is that the anterolateral branch of the anterior humeral circumflex artery provides the main blood supply to the humeral head. While the artery is disrupted in association with 80% of proximal humeral fractures, resultant osteonecrosis is infrequent. This inconsistency suggests a greater role for the posterior humeral circumflex artery than has been previously described. We hypothesized that the posterior humeral circumflex artery provides a greater percentage of perfusion to the humeral head than the anterior humeral circumflex artery does. METHODS: In twenty-four fresh frozen cadaver shoulders (twelve matched pairs), we cannulated the axillary artery proximal to the thoracoacromial branch and ligated the brachial artery in the forearm. In each pair, one shoulder served as a control with intact vasculature and, in the contralateral shoulder, either the anterior humeral circumflex artery or the posterior humeral circumflex artery was ligated. Gadolinium was injected through the cannulated axillary arteries, and magnetic resonance imaging was performed. After imaging, a urethane polymer was injected, and specimens were dissected. For volumetric analysis, the gadolinium uptake on the magnetic resonance imaging was quantified in each quadrant of the humeral head with use of a custom automated program. The gadolinium uptake was compared between the control and ligated sides and between the ligated anterior humeral circumflex artery and ligated posterior humeral circumflex artery groups. RESULTS: The posterior humeral circumflex artery provided 64% of the blood supply to the humeral head overall, whereas the anterior humeral circumflex artery supplied 36%. The posterior humeral circumflex artery also provided significantly more of the blood supply in three of the four quadrants of the humeral head. CONCLUSIONS: The finding that the posterior humeral circumflex artery provides 64% of the blood supply to the humeral head provides a possible explanation for the relatively low rates of osteonecrosis seen in association with displaced fractures of the proximal part of the humerus. In addition, protecting the posterior humeral circumflex artery during the surgical approach and fracture fixation may minimize loss of the blood supply to the humeral head. PMID- 20360520 TI - Contribution of the olecranon to elbow stability: an in vitro biomechanical study. AB - BACKGROUND: The amount of the olecranon that can be removed without substantially affecting the kinematics and stability of the elbow is controversial. The purpose of this study was to determine the effect of serial resections of the olecranon on elbow kinematics and stability. METHODS: Eight fresh, previously frozen cadaver arms were mounted in an in vitro motion simulator, and kinematic data were obtained with use of an electromagnetic tracking system for active and passive motion. Flexion was studied in the varus, valgus, horizontal, and dependent positions. Custom-written three-dimensional computer navigation software was utilized to guide serial resection of the olecranon in 12.5% increments from 0% to 100%. A traditional triceps advancement repair was performed following each resection. Flexion angle, amount of olecranon resection, and active and passive motion measurements were compared. RESULTS: Serial resection of the olecranon resulted in a significant increase in varus-valgus angulation with the arm in the varus (p < 0.04) and valgus (p = 0.01) orientations. Ulnohumeral rotation significantly increased in the varus (p < 0.001) and valgus (p < 0.007) orientations. Angular (p = 0.02) and rotational (p < 0.001) kinematics were greater with passive compared with active motion. There was no difference in elbow kinematics following olecranon resection with the arm positioned in the horizontal and dependent positions. CONCLUSIONS: Valgus-varus angulation and ulnohumeral rotation progressively increase with sequential excision of up to 75% of the olecranon. Elbow stability is progressively lost with sequential excision, with gross instability noted at resection of > or = 87.5% of the olecranon. PMID- 20360521 TI - Complete disassembly of the Coonrad-Morrey elbow replacement: a case report. PMID- 20360522 TI - Femoral condylar fracture through a femoral tunnel eleven years after anterior cruciate ligament reconstruction: a case report. PMID- 20360523 TI - The Pirogoff amputation for necrosis of the forefoot: a case report. PMID- 20360524 TI - Treatment of traumatic separation of the proximal femoral epiphysis without development of osteonecrosis: a report of two cases. PMID- 20360525 TI - Common peroneal nerve compression and heterotopic ossification resulting from severe burn injury: a case report. PMID- 20360526 TI - Monostotic fibrous dysplasia of the spine: a report of seven cases. PMID- 20360527 TI - American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of osteoarthritis (OA) of the knee. PMID- 20360528 TI - Management of articular cartilage defects of the knee. AB - Articular cartilage has a poor intrinsic capacity for healing. The goal of surgical techniques to repair articular cartilage injuries is to achieve the regeneration of organized hyaline cartilage. Microfracture and other bone marrow stimulation techniques involve penetration of the subchondral plate in order to recruit mesenchymal stem cells into the chondral defect. The formation of a stable clot that fills the lesion is of paramount importance to achieve a successful outcome. Mosaicplasty is a viable option with which to address osteochondral lesions of the knee and offers the advantage of transplanting hyaline cartilage. However, limited graft availability and donor site morbidity are concerns. Transplantation of an osteochondral allograft consisting of intact, viable articular cartilage and its underlying subchondral bone offers the ability to address large osteochondral defects of the knee, including those involving an entire compartment. The primary theoretical advantage of autologous chondrocyte implantation is the development of hyaline-like cartilage rather than fibrocartilage in the defect, which presumably leads to better long-term outcomes and longevity of the healing tissue. Use of synthetic scaffolds is a potentially attractive alternative to traditional cartilage procedures as they are readily available and, unlike allogeneic tissue transplants, are associated with no risk of disease transmission. Their efficacy, however, has not been proven clinically. PMID- 20360529 TI - Repair of complex and avascular meniscal tears and meniscal transplantation. PMID- 20360530 TI - The evidence-based approach in bringing new orthopaedic devices to market. PMID- 20360532 TI - The future of the orthopaedic clinician-scientist: part II: Identification of factors that may influence orthopaedic residents' intent to perform research. AB - BACKGROUND: The successful incorporation of research into the future careers of residents provides tremendous potential for increasing scientific orthopaedic inquiry and improving musculoskeletal care. Therefore, we sought to assess resident opinions regarding plans and incentives for future research and the opinions of academic chairs who must support them. METHODS: Residents from sixteen departments were surveyed with a twenty-four-question online survey. Similar surveys were sent to chairs of all residency-sponsoring departments. RESULTS: The response rate was 44% (183) for the residents and 60% (eighty-six) for the chairs. Forty-two percent of the residents felt certain or likely that they would perform research during their careers, and 28% were undecided. Ninety nine percent thought that orthopaedic surgeons performing research is important to clinical orthopaedics. Ninety-three percent of the residents expressed the need for monetary incentives for research, but only 40% would help to provide it. Chairs similarly noted the importance of research subsidization (92%) and a willingness to support it (70%). Residents indicated that increased funding and protected time would provide the greatest incentives for research during residency; chairs agreed. After training, debt relief and salary support were most important for residents; chairs chose protected time and a chair who is supportive of research as most important. Primary authorship on a prior manuscript and past research experience were found to be associated with greater future research interest in univariate analyses; primary authorship maintained an independent association in multivariate analysis. Younger residents and women were more likely to be unsure of their research interest. CONCLUSIONS: Many orthopaedic residents in training have interest in integrating research into their future practice and support the research mission of orthopaedic surgeons. Our results may aid in identifying residents with high research interest (and those unsure) and help to guide the provision of incentives to actuate those interests. PMID- 20360533 TI - What's new in shoulder and elbow surgery. PMID- 20360534 TI - Re: Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting. PMID- 20360536 TI - Atherosclerosis in abdominal aortic aneurysms: a causal event or a process running in parallel? The Tromso study. AB - OBJECTIVE: The pathogenesis of abdominal aortic aneurysm (AAA) formation is poorly understood. We investigated the relationship between carotid, femoral, and coronary atherosclerosis and abdominal aortic diameter, and whether atherosclerosis was a risk marker for AAA. METHODS AND RESULTS: Ultrasound of the right carotid artery, the common femoral artery, and the abdominal aorta was performed in 6446 men and women from a general population. The burden of atherosclerosis was assessed as carotid total plaque area, common femoral lumen diameter, and self-reported coronary heart disease. An AAA was defined as maximal infrarenal aortic diameter > or =30 mm. No dose-response relationship was found between carotid atherosclerosis and abdominal aortic diameter <27 mm. However, significantly more atherosclerosis and coronary heart disease was found in aortic diameter > or =27 mm and in AAAs. The age- and sex-adjusted odds ratio (OR) (95% CI) for AAA in the top total plaque area quintile was 2.3 (1.5 to 3.4), as compared with subjects without plaques. The adjusted OR (95% CI) was 1.7 (1.1 to 2.6). No independent association was found between femoral lumen diameter and AAA. CONCLUSIONS: The lack of a consistent dose-response relationship between atherosclerosis and abdominal aortic diameter suggests that atherosclerosis may not be a causal event in AAA but develops in parallel with or secondary to aneurismal dilatation. PMID- 20360535 TI - Glucose-regulated protein 78 and platelet deposition: effect of rosuvastatin. AB - OBJECTIVE: To investigate the effect of rosuvastatin on platelet deposition under controlled shear rate conditions and to identify new platelet proteins involved in the interaction with the activating substrate. METHODS AND RESULTS: Platelet vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulating blood cells and proteins. Blood was perfused over type I collagen at different wall shear rates, and platelet deposition was measured by confocal microscopy. Perfused effluent blood was collected, platelets were sequentially extracted based on differential protein solubility, and proteins were separated by 2D gel electrophoresis. Blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase significantly reduced platelet deposition and modulated the expression pattern of 18 proteins in the platelet subproteome. Among them, an increase in platelet surface 78-kDa glucose-regulated protein (GRP78), a stress-inducible multifunctional endoplasmic reticulum protein, was clearly apparent. Immunoprecipitation of platelet GRP78 revealed its interaction with tissue factor. Moreover, blockade of surface GRP78 resulted in a substantial increase in platelet deposition and tissue factor procoagulant activity and in a decrease in clotting time. CONCLUSIONS: These findings demonstrate that blockade of 3-hydroxy 3-methylglutaryl-coenzyme A reductase reduces platelet deposition and inhibits GRP78 translocation from the platelet surface after shear and collagen activation. For the first time to our knowledge, this study reports on the presence and functional role of GRP78 in platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone. PMID- 20360539 TI - Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. AB - BACKGROUND AND PURPOSE: Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium. METHODS: In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured alpha-galactosidase A (alpha-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the alpha-GAL A gene. RESULTS: alpha-GAL A activity was deficient in 19 men (3.5%), although all had normal alpha-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease. CONCLUSIONS: alpha-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases. PMID- 20360537 TI - Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia. AB - OBJECTIVE: To investigate the novel hypothesis that neurotrophin-3 (NT-3), an established neurotrophic factor that participates in embryonic heart development, promotes blood vessel growth. METHODS AND RESULTS: We evaluated the proangiogenic capacity of recombinant NT-3 in vitro and of NT-3 gene transfer in vivo (rat mesenteric angiogenesis assay and mouse normoperfused adductor muscle). Then, we studied whether either transgenic or endogenous NT-3 mediates postischemic neovascularization in a mouse model of limb ischemia. In vitro, NT-3 stimulated endothelial cell survival, proliferation, migration, and network formation on the basement membrane matrix Matrigel. In the mesenteric assay, NT-3 increased the number and size of functional vessels, including vessels covered with mural cells. Consistently, NT-3 overexpression increased muscular capillary and arteriolar densities in either the absence or the presence of ischemia and improved postischemic blood flow recovery in mouse hind limbs. NT-3-induced microvascular responses were accompanied by tropomyosin receptor kinase C (an NT 3 high-affinity receptor) phosphorylation and involved the phosphatidylinositol 3 kinase-Akt kinase-endothelial nitric oxide synthase pathway. Finally, endogenous NT-3 was shown to be essential in native postischemic neovascularization, as demonstrated by using a soluble tropomyosin receptor kinase C receptor domain that neutralizes NT-3. CONCLUSIONS: Our results provide the first insight into the proangiogenic capacity of NT-3 and propose NT-3 as a novel potential agent for the treatment of ischemic disease. PMID- 20360538 TI - Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study. AB - BACKGROUND AND PURPOSE: Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function. METHODS: This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function. RESULTS: Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes. CONCLUSIONS: In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology. PMID- 20360540 TI - Preservation of GABAA receptor function by PTEN inhibition protects against neuronal death in ischemic stroke. AB - BACKGROUND AND PURPOSE: Downregulation of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is thought to be a novel neuroprotective strategy in ischemic stroke, but the underlying mechanisms remain unclear. In this study, we aimed to validate the use of PTEN regulation of gamma aminobutyric acid subtype A receptors (GABA(A)Rs) as a molecular target for the treatment of ischemic stroke. Because suppression of GABA(A)Rs contributes to ischemic neuron death, describing the intracellular signaling that interacts with GABA(A)Rs in ischemic neurons would provide a molecular basis for novel stroke therapies. METHODS: We measured surface GABA(A)R expression by immunocytochemical labeling and surface protein biotinylation assay. Knockdown and overexpression approaches were used to test the effects of PTEN on the expression and function of GABA(A)Rs. Neuronal death was detected in both in vitro and in vivo stroke models. RESULTS: The knockdown and overexpression approaches provided the first evidence that PTEN negatively regulated membrane expression and function of GABA(A)Rs in rat hippocampal neurons. Importantly, we demonstrated that a PTEN inhibitor prevented the reduction of surface GABA(A)Rs in injured hippocampal neurons subjected to oxygen-glucose deprivation, an in vitro insult that mimics ischemic injury, whereas a GABA(A)R antagonist significantly reduced this PTEN inhibitor-induced neuroprotection in both the in vitro and in vivo ischemic stroke models. CONCLUSIONS: Our study provides direct evidence that downregulation of PTEN protects against ischemic neuron death by preserving GABA(A)R function. Targeting this pathway may be an effective strategy for development of selective, potent stroke treatments. PMID- 20360542 TI - Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. AB - BACKGROUND AND PURPOSE: Case reports or case series have reported the association between hyperthyroidism and cerebrovascular disease. However, hyperthyroidism has never been considered as a potential risk factor for stroke in young people. The aim of the present study is to estimate the risk for ischemic stroke among hyperthyroidism patients aged 18 to 44 years during a 5-year period after the diagnosis of hyperthyroidism as compared to a cohort of patients without hyperthyroidism during the same period. METHODS: A total of 3176 patients with hyperthyroidism were included as the study cohort and 25 408 patients without hyperthyroidism were included as comparison cohort. Each patient was individually tracked for 5 years from their index ambulatory visit to identify those in whom ischemic stroke developed. Cox proportional hazard regressions were performed to compute the 5-year stroke-free survival rate between these 2 cohorts. RESULTS: Of the total sample of 28 584 patients, 198 patients (0.7%) had ischemic strokes during the 5-year follow-up period (31 [1.0% of the hyperthyroidism patients] from the study cohort and 167 [0.6% of comparison patients] from the comparison cohort). After adjusting for the patient's age, gender, income, level of urbanization, hypertension, diabetes, atrial fibrillation, hyperlipidemia, coronary heart disease, and whether they were using antiarrhythmics, the hazard of having ischemic stroke during the 5-year follow-up period was 1.44-times greater (95% CI, 1.02-2.12; P=0.038) for patients with hyperthyroidism than for patients in the comparison cohort. CONCLUSIONS: We conclude that hyperthyroidism is associated with an increased risk for ischemic stroke among young adults. PMID- 20360541 TI - Intra-arterial iodinated radiographic contrast material injection administration in a rat middle cerebral artery occlusion and reperfusion model: possible effects on intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: Observations in human interventional stroke treatment led us to hypothesize that iodinated radiographic contrast material use may contribute to intracerebral hemorrhage. Effects of intra-arterial iodinated radiographic contrast material on hemorrhagic transformation after middle cerebral artery occlusion and reperfusion were studied in a placebo-controlled, blinded preclinical study in rats. METHODS: Four groups of male Sprague-Dawley rats were studied: saline group (n=8), contrast group (n=12), heparin group (n=9), and contrast+heparin group (n=9). The middle cerebral artery was occluded for 5 hours using suture placement. Heparin was infused before suture removal and reperfusion. Saline and/or contrast were infused immediately during reperfusion. Incidence, location, and size of hemorrhage were determined by brain necropsy inspection at 24 hours. RESULTS: There was a significant increase in incidence of cortical hemorrhage from control (37.5%), contrast (75.0%), heparin (77.8%) to contrast+heparin (100%; Cochran-Mantel-Haenszel correlation, P<0.01). Both pooled contrast groups (85.7%) and pooled heparin groups (88.9%) had higher rates of cortical intracerebral hemorrhage compared with the control group (P<0.05). Similar trends for increased cortical intracerebral hemorrhage were seen in the contrast-only (P=0.18) and heparin-only (P=0.18) groups. There was a trend for decreased infarct edema in rats receiving contrast versus those without (P=0.06). CONCLUSIONS: Intraarterial iodinated radiographic contrast material may increase cortical intracerebral hemorrhage, similar to heparin. Iodinated radiographic contrast material effect may be additive to heparin effect on the incidence of cortical intracerebral hemorrhage. PMID- 20360543 TI - Hospitalized stroke surveillance in the community of Durango, Mexico: the brain attack surveillance in Durango study. AB - BACKGROUND AND PURPOSE: Vascular conditions are becoming the greatest cause of morbidity and mortality in developing countries. Few studies exist in Latin America. We aimed to perform a rigorous stroke surveillance study in Durango, Mexico. METHODS: Active and passive surveillance were used to identify all patients with potential stroke presenting to Durango Municipality hospitals from August 2007 to July 2008. Exclusion criteria were subjects younger than 25 years old, stroke attributable to head trauma, and non-Durango Municipality residents. Brain Attack Surveillance in Durango-trained neurologists validated cases as stroke using source documentation. Stroke hospitalization rates were defined to include patients examined in the emergency department or admitted to the hospital. RESULTS: Abstractors identified 435 potential cases; 309 (71%) were validated as stroke. Of the validated stroke cases, the median age was 71 and 49% were female. Subtypes were 61.5% ischemic stroke, 20.7% intracerebral hemorrhage, 7.4% subarachnoid hemorrhage, and 10.4% undetermined. Overall initial NIHSS was a median of 11 (interquartile range, 7-17); in-hospital mortality was 39%. When adjusted to the world population, the age-adjusted hospitalization rate of first ever stroke was 118.2 per 100 000; rates by type were: ischemic stroke, 69.1 (95% CI, 57.5-80.7); intracerebral hemorrhage, 26.7 (95% CI, 19.6-33.8); subarachnoid hemorrhage, 9.5 (95% CI, 5.3-13.8); and unknown, 12.3 (95% CI, 7.4-17.3). Of 190 patients with validated ischemic stroke, 44.2% received lipid testing and 7.4% received carotid imaging and echocardiography; 1.1% received tissue plasminogen activator. CONCLUSIONS: To our knowledge, this is the first estimate of stroke hospitalization rates in a Mexican community and it provides information important for design of interventions to prevent and treat stroke. This information is critical to reduce Mexico's stroke burden. PMID- 20360544 TI - Autopsy findings after intracranial thrombectomy for acute ischemic stroke: a clinicopathologic study of 5 patients. AB - BACKGROUND AND PURPOSE: Endovascular thrombectomy is an increasingly used treatment for arterial occlusion in acute stroke. Various devices (including most extensively the Mechanical Embolus Removal in Cerebral Ischemia [MERCI] Retriever device) have been used for this. METHODS: We review the neuropathologic findings in 5 patients (age range, 59 to 87 years) who died acutely or as late as 38 days after procedures using the MERCI (4 patients) and Penumbra (1 patient) devices were carried out to remove thromboemboli from the middle cerebral artery. Partial recanalization was achieved by thrombectomy in all 5 patients. RESULTS: All patients showed extensive cerebral infarcts, 3 of 5 with clinical hemorrhagic transformations of the infarct or frank intraparenchymal hemorrhage after thrombectomy; in 1 case, this was judged to be at least partly on the basis of concomitant hypertensive microvascular disease. With 1 exception, basal arteries examined in detail by immunohistochemistry showed prominent, although usually nonocclusive (and generally nonulcerated), atheromata, often with significant luminal stenosis. One patient showed a subintimal dissection with resultant occlusion of the middle cerebral artery. CONCLUSIONS: In this highly selected group of patients, the vascular pathological abnormalities affecting basal arteries were variable, but complicated atherosclerosis was a common finding. Extensive irreversible brain necrosis before therapeutic procedures may have contributed to deaths. PMID- 20360545 TI - Is health-related quality of life improving after stroke? A comparison of health utilities indices among Canadians with stroke between 1996 and 2005. AB - BACKGROUND AND PURPOSE: Recent innovations in diagnosis, management, and rehabilitation have resulted in measurable improvements in clinical and functional outcomes after acute stroke. However, whether gains in health-related quality of life after stroke have also occurred is not well characterized. Using 2 Canadian population surveys, the purpose of this study was to identify changes in health-related quality of life in individuals with stroke from 1996 to 2005. METHODS: Data from the public use files of the National Population Health Survey, Cycle 2 (1996), and the Canadian Community Health Survey, Cycle 3.1. (2005), were used. A total of 847 individuals with stroke were included. Self-reported information on health status based on the Health Utilities Index Mark 3 was used to generate single-attribute and overall health-related quality of life scores. Analysis of covariance and multiple logistic regression were used to determine the relationship between survey year and poststroke impairment adjusting for demographic variables and clinical comorbidities. RESULTS: A statistically significant and clinically important reduction in mean overall Health Utilities Index Mark 3 scores was observed for respondents with stroke from 1996 to 2005. In addition, 2 of the 8 single-attribute Health Utilities Index Mark 3 domains showed a significant change between survey years. Significantly more individuals with stroke reported dexterity and cognitive impairment in 2005 compared with respondents in 1996, indicating reduced health-related quality of life for these domains. CONCLUSIONS: Despite improvements in medical management, quality of life is not improving after stroke in the Canadian population. These findings are useful to generate hypotheses about the impact of advances in management on quality of life after stroke and identify specific domains that may benefit from future study in stroke populations. PMID- 20360546 TI - Effects of granulocyte-colony stimulating factor after stroke in aged rats. AB - BACKGROUND AND PURPOSE: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. Granulocyte-colony stimulating factor (G-CSF), a member of the cytokine family of growth factors, promotes brain neurogenesis and improves functional outcome after stroke in young animals. We tested the hypothesis that G-CSF provides a restorative therapeutic benefit in aged animals. METHODS: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 19- to 20-month-old male Sprague Dawley rats. One hour after reperfusion, the aged rats were treated daily with 15 microg/kg G-CSF and for 15 days total. Rats were behaviorally tested and the brains removed for analysis at 28 days poststroke. RESULTS: G-CSF treatment after stroke exerted a robust and sustained beneficial effect on survival rate and running function. Transient improvement after G-CSF treatment could be observed for coordinative motor function on the inclined plane test and for working memory in the radial-arm maze test. At the cellular level, G-CSF treatment increased the number of proliferating cells in the subventricular zone and dentate gyrus and also increased the number of newborn neurons in the subventricular zone ipsilateral to the lesion. CONCLUSIONS: These results suggest that G-CSF treatment in aged rats has a survival-enhancing capacity and a beneficial effect on functional outcome, most likely through supportive cellular processes such as neurogenesis. PMID- 20360547 TI - Intercellular adhesion molecule-1 G241R polymorphism predicts risk of incident ischemic stroke: Atherosclerosis Risk in Communities study. PMID- 20360548 TI - Combination of tissue-plasminogen activator with erythropoietin induces blood brain barrier permeability, extracellular matrix disaggregation, and DNA fragmentation after focal cerebral ischemia in mice. AB - BACKGROUND AND PURPOSE: After 1 clinical study in which recombinant erythropoietin (EPO) protected against ischemic stroke and improved clinical outcome, the German multicenter EPO trial recently reported increased mortality in stroke patients receiving EPO after tissue-plasminogen activator (t-PA) induced thrombolysis. The reasons for the adverse effects of EPO in t-PA-treated patients are unknown. METHODS: Mice were submitted to 90 minutes of middle cerebral artery occlusion. Immediately after reperfusion, animals were treated with normal saline or t-PA (10 mg/kg). Animals subsequently received injections of normal saline or EPO that were administered after reperfusion and 12 hours later (2500 IU/kg each). Ischemic injury and brain edema were analyzed at 24 hours after reperfusion by cresyl violet staining and terminal transferase biotinylated-dUTP nick end labeling. Blood-brain barrier integrity was assessed by histochemistry for extravasated serum IgG. Matrix metalloproteinase activity was evaluated by gelatinase zymography. RESULTS: EPO did not influence ischemic infarct size but reduced brain swelling. This effect was abolished by t-PA, which exacerbated serum IgG extravasation in ischemic tissue. Gelatinase zymographies revealed that EPO promoted matrix metalloproteinase-9 activity that was markedly elevated by t-PA. Add-on treatment with t-PA increased the density of DNA fragmented cells in ischemic tissue of EPO-treated, but not vehicle-treated, mice. CONCLUSIONS: Our data demonstrate a hitherto unknown interaction of t-PA with EPO at the blood-brain interface, ie, promotion of vascular permeability and extracellular matrix breakdown, which may account for the unfavorable actions of EPO in t-PA-treated patients. After t-PA-induced thrombolysis, EPO may not be suitable as stroke treatment. PMID- 20360549 TI - Efficacy of intra-arterial fibrinolysis for acute ischemic stroke: meta-analysis of randomized controlled trials. AB - BACKGROUND AND PURPOSE: Although intra-arterial (IA) fibrinolysis for acute ischemic stroke has been clinically available for many years, it is not a therapy approved by the US Food and Drug Administration. Single, randomized, clinical trials (RCTs) have suggested beneficial effects, but no single RCT has demonstrated that IA fibrinolysis yields increases in both good (modified Rankin Scale score 0 to 2) and excellent (modified Rankin Scale score 0 to 1) outcomes when compared with the control group. Relatively few participants and inadequate statistical power in single RCTs may have contributed to this difficulty. Method- We performed a systematic literature search to identified RCTs of IA fibrinolysis in acute ischemic stroke. Multiple outcomes were analyzed, with emphasis on good and excellent outcomes at 90 days or at trial end point. RESULTS: The systematic search identified 5 RCTs with 395 participants comparing IA fibrinolysis and control. IA fibrinolysis was associated with increased good (odds ratio=2.05; 95% CI, 1.33 to 3.14; P=0.001) and excellent (odds ratio=2.14; 95% CI, 1.31 to 3.51; P=0.003) outcomes. For additional end points, IA fibrinolysis was associated with increased frequencies of minimal neurologic deficit (National Institutes of Health Stroke Scale score 0 to 1), minimal impairment of activities of daily living (Barthel Index 90 to 100 or 95 to 100), and recanalization. IA fibrinolysis was associated with increased radiological and symptomatic intracerebral hemorrhage. However, there was no difference in mortality between groups. CONCLUSIONS: Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke. Increased hemorrhage frequencies are not associated with any increase in mortality. PMID- 20360550 TI - Key role of CD36 in Toll-like receptor 2 signaling in cerebral ischemia. AB - BACKGROUND AND PURPOSE: Toll-like receptors (TLRs) and the scavenger receptor CD36 are key molecular sensors for the innate immune response to invading pathogens. However, these receptors may also recognize endogenous "danger signals" generated during brain injury, such as cerebral ischemia, and trigger a maladaptive inflammatory reaction. Indeed, CD36 and TLR2 and 4 are involved in the inflammation and related tissue damage caused by brain ischemia. Because CD36 may act as a coreceptor for TLR2 heterodimers (TLR2/1 or TLR2/6), we tested whether such interaction plays a role in ischemic brain injury. METHODS: The TLR activators FSL-1 (TLR2/6), Pam3 (TLR2/1), or lipopolysaccharide (TLR4) were injected intracerebroventricularly into wild-type or CD36-null mice, and inflammatory gene expression was assessed in the brain. The effect of TLR activators on the infarct produced by transient middle cerebral artery occlusion was also studied. RESULTS: The inflammatory response induced by TLR2/1 activation, but not TLR2/6 or TLR4 activation, was suppressed in CD36-null mice. Similarly, TLR2/1 activation failed to increase infarct volume in CD36-null mice, whereas TLR2/6 or TLR4 activation exacerbated postischemic inflammation and increased infarct volume. In contrast, the systemic inflammatory response evoked by TLR2/6 activation, but not by TLR2/1 activation, was suppressed in CD36-null mice. CONCLUSIONS: In the brain, TLR2/1 signaling requires CD36. The cooperative signaling of TLR2/1 and CD36 is a critical factor in the inflammatory response and tissue damage evoked by cerebral ischemia. Thus, suppression of CD36-TLR2/1 signaling could be a valuable approach to minimize postischemic inflammation and the attendant brain injury. PMID- 20360551 TI - Improving the reliability of stroke disability grading in clinical trials and clinical practice: the Rankin Focused Assessment (RFA). AB - BACKGROUND AND PURPOSE: The modified Rankin Scale rates global disability after stroke and is the most comprehensive and widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability in modified Rankin Scale scoring has been reported. This study sought to develop and validate a short, practicable structured assessment that would enhance interrater reliability. METHODS: The Rankin Focused Assessment was developed by selecting and refining elements from prior instruments. The Rankin Focused Assessment takes 3 to 5 minutes to apply and provides clear, operationalized criteria to distinguish the 7 assignable global disability levels. The Rankin Focused Assessment was prospectively validated 3 months poststroke among 50 consecutive patients enrolled in the Phase 3 National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial. RESULTS: Among the 50 patients, mean age was 71.5 years (range, 43 to 93 years), 48% were female, and stroke subtype was hemorrhagic in 24%. At Day 90, 43 patients were alive and 7 had died. The modified Rankin Scale median was 2.0 and mean was 2.8. When pairs of 14 raters assessed all enrolled patients, the percent agreement was 94%, the weighted kappa was 0.99 (95% CI, 0.99 to 1.0), and the unweighted kappa was 0.93 (95% CI, 0.85 to 1.00). Among the 43 surviving patients, the percent agreement was 93%, the weighted kappa was 0.99 (0.98 to 1.0), and the unweighted kappa was 0.91 (0.82 to 1.00). CONCLUSIONS: The Rankin Focused Assessment yields high interrater reliability in the grading of final global disability among consecutive patients with stroke participating in a randomized clinical trial. The Rankin Focused Assessment is brief and practical for use in multicenter clinical trials and quality improvement activities. PMID- 20360552 TI - Baroreflex, cerebral perfusion, and stroke: integrative physiology at its best. PMID- 20360553 TI - Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury. AB - BACKGROUND AND PURPOSE: Neuronal replacement has recently gained attention as a potential therapeutic target under ischemic conditions. However, the oligodendrogenic infrastructure is equally critical for restoration of brain function and is also sensitive to ischemic injury. Erythropoietin (EPO) is a neuroprotective molecule that stimulates neuronal replacement after neonatal hypoxia/ischemia (H/I) when delivered soon after the onset of reperfusion. Because EPO can improve recovery of neurological function in the absence of tissue protection, we hypothesize that EPO may improve neurological function via enhancement of white matter recovery after H/I. Thus, we sought to determine the effects of delayed administration of EPO on white matter injury and recovery of neurological function after neonatal H/I. METHODS: EPO (1000 U/kg) was injected intraperitoneally at multiple time points beginning 48 hours after H/I in postnatal day 7 rats. The effects of EPO on oligodendrogenesis, white matter injury, and neurogenesis were evaluated using bromodeoxyuridine incorporation and cell-specific immunohistochemistry. Neurological function was assessed by sensorimotor behavioral tests. RESULTS: Delayed administration of EPO was incapable of reducing brain volume loss but significantly increased oligodendrogenesis and maturation of oligodendrocytes and attenuated white matter injury after H/I. These effects occurred concurrently with enhanced neurogenesis. Delayed EPO treatment improved behavioral neurological outcomes 14 days after H/I injury. CONCLUSIONS: Our study demonstrates that delayed administration of EPO promotes oligodendrogenesis and attenuates white matter injury concurrently with increased neurogenesis. These effects likely contribute to the observed improvement in neurological functional outcomes. PMID- 20360554 TI - Harnessing the power of the human microbiome. PMID- 20360555 TI - Synaptic dynamics and decision making. AB - During decision making between sequential stimuli, the first stimulus must be held in memory and then compared with the second. Here, we show that in systems that encode the stimuli by their firing rate, neurons can use synaptic facilitation not only to remember the first stimulus during the delay but during the presentation of the second stimulus so that they respond to a combination of the first and second stimuli, as has been found for "partial differential" neurons recorded in the ventral premotor cortex during vibrotactile flutter frequency decision making. Moreover, we show that such partial differential neurons provide important input to a subsequent attractor decision-making network that can then compare this combination of the first and second stimuli with inputs from other neurons that respond only to the second stimulus. Thus, both synaptic facilitation and neuronal attractor dynamics can account for sequential decision making in such systems in the brain. PMID- 20360556 TI - Mass extinctions of life and catastrophic flood basalt volcanism. PMID- 20360557 TI - Nuclear envelope and lamin B2 function in the central nervous system. PMID- 20360558 TI - Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. AB - The indigenous bacteria create natural cohabitation niches together with mucosal Abs in the gastrointestinal (GI) tract. Here we report that opportunistic bacteria, largely Alcaligenes species, specifically inhabit host Peyer's patches (PPs) and isolated lymphoid follicles, with the associated preferential induction of antigen-specific mucosal IgA Abs in the GI tract. Alcaligenes were identified as the dominant bacteria on the interior of PPs from naive, specific-pathogen free but not from germ-free mice. Oral transfer of intratissue uncultured Alcaligenes into germ-free mice resulted in the presence of Alcaligenes inside the PPs of recipients. This result was further supported by the induction of antigen-specific Ab-producing cells in the mucosal (e.g., PPs) but not systemic compartment (e.g., spleen). The preferential presence of Alcaligenes inside PPs and the associated induction of intestinal secretory IgA Abs were also observed in both monkeys and humans. Localized mucosal Ab-mediated symbiotic immune responses were supported by Alcaligenes-stimulated CD11c(+) dendritic cells (DCs) producing the Ab-enhancing cytokines TGF-beta, B-cell-activating factor belonging to the TNF family, and IL-6 in PPs. These CD11c(+) DCs did not migrate beyond the draining mesenteric lymph nodes. In the absence of antigen-specific mucosal Abs, the presence of Alcaligenes in PPs was greatly diminished. Thus, indigenous opportunistic bacteria uniquely inhabit PPs, leading to PP-DCs-initiated, local antigen-specific Ab production; this may involve the creation of an optimal symbiotic environment on the interior of the PPs. PMID- 20360559 TI - Inhibitor-induced structural change in the HCV IRES domain IIa RNA. AB - Translation of the hepatitis C virus (HCV) RNA is initiated from a highly structured internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) of the RNA genome. An important structural feature of the native RNA is an approximately 90 degrees helical bend localized to domain IIa that positions the apical loop of domain IIb of the IRES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly. We report here the NMR structure of a domain IIa construct in complex with a potent small-molecule inhibitor of HCV replication. Molecular dynamics refinement in explicit solvent and subsequent energetic analysis indicated that each inhibitor stereoisomer bound with comparable affinity and in an equivalent binding mode. The in silico analysis was substantiated by fluorescence-based assays showing that the relative binding free energies differed by only 0.7 kcal/mol. Binding of the inhibitor displaces key nucleotide residues within the bulge region, effecting a major conformational change that eliminates the bent RNA helical trajectory, providing a mechanism for the antiviral activity of this inhibitor class. PMID- 20360560 TI - Simulated atmospheric processing of iron oxyhydroxide minerals at low pH: roles of particle size and acid anion in iron dissolution. AB - A number of recent studies have shown that iron dissolution in Fe-containing dust aerosol can be linked to source material (mineral or anthropogenic), mineralogy, and iron speciation. All of these factors need to be incorporated into atmospheric chemistry models if these models are to accurately predict the impact of Fe-containing dusts into open ocean waters. In this report, we combine dissolution measurements along with spectroscopy and microscopy to focus on nanoscale size effects in the dissolution of Fe-containing minerals in low-pH environments and the importance of acid type, including HNO(3), H(2)SO(4), and HCl, on dissolution. All of these acids are present in the atmosphere, and dust particles have been shown to be associated with nitrate, sulfate, and/or chloride. These measurements are done under light and dark conditions so as to simulate and distinguish between daytime and nighttime atmospheric chemical processing. Both size (nano- versus micron-sized particles) and anion (nitrate, sulfate, and chloride) are found to play significant roles in the dissolution of alpha-FeOOH under both light and dark conditions. The current study highlights these important, yet unconsidered, factors in the atmospheric processing of iron containing mineral dust aerosol. PMID- 20360562 TI - X-ray emission processes in stars and their immediate environment. AB - A decade of X-ray stellar observations with Chandra and XMM-Newton has led to significant advances in our understanding of the physical processes at work in hot (magnetized) plasmas in stars and their immediate environment, providing new perspectives and challenges, and in turn the need for improved models. The wealth of high-quality stellar spectra has allowed us to investigate, in detail, the characteristics of the X-ray emission across the Hertzsprung-Russell (HR) diagram. Progress has been made in addressing issues ranging from classical stellar activity in stars with solar-like dynamos (such as flares, activity cycles, spatial and thermal structuring of the X-ray emitting plasma, and evolution of X-ray activity with age), to X-ray generating processes (e.g., accretion, jets, magnetically confined winds) that were poorly understood in the preChandra/XMM-Newton era. I will discuss the progress made in the study of high energy stellar physics and its impact in a wider astrophysical context, focusing on the role of spectral diagnostics now accessible. PMID- 20360561 TI - Bayesian approach to transforming public gene expression repositories into disease diagnosis databases. AB - The rapid accumulation of gene expression data has offered unprecedented opportunities to study human diseases. The National Center for Biotechnology Information Gene Expression Omnibus is currently the largest database that systematically documents the genome-wide molecular basis of diseases. However, thus far, this resource has been far from fully utilized. This paper describes the first study to transform public gene expression repositories into an automated disease diagnosis database. Particularly, we have developed a systematic framework, including a two-stage Bayesian learning approach, to achieve the diagnosis of one or multiple diseases for a query expression profile along a hierarchical disease taxonomy. Our approach, including standardizing cross-platform gene expression data and heterogeneous disease annotations, allows analyzing both sources of information in a unified probabilistic system. A high level of overall diagnostic accuracy was shown by cross validation. It was also demonstrated that the power of our method can increase significantly with the continued growth of public gene expression repositories. Finally, we showed how our disease diagnosis system can be used to characterize complex phenotypes and to construct a disease-drug connectivity map. PMID- 20360563 TI - Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation. AB - Autotaxin (ATX) is a secreted nucleotide pyrophosphatase/phosphodiesterase that functions as a lysophospholipase D to produce the lipid mediator lysophosphatidic acid (LPA), a mitogen, chemoattractant, and survival factor for many cell types. The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation, fibrotic diseases and tumor progression, making this system an attractive target for therapy. However, potent and selective nonlipid inhibitors of ATX are currently not available. By screening a chemical library, we have identified thiazolidinediones that selectively inhibit ATX-mediated LPA production both in vitro and in vivo. Inhibitor potency was approximately 100 fold increased (IC(50) approximately 30 nM) after the incorporation of a boronic acid moiety, designed to target the active-site threonine (T210) in ATX. Intravenous injection of this inhibitor into mice resulted in a surprisingly rapid decrease in plasma LPA levels, indicating that turnover of LPA in the circulation is much more dynamic than previously appreciated. Thus, boronic acid based small molecules hold promise as candidate drugs to target ATX. PMID- 20360564 TI - Salmonella-mediated delivery of RNase P-based ribozymes for inhibition of viral gene expression and replication in human cells. AB - A fundamental challenge in gene therapy is to develop approaches for delivering nucleic acid-based gene interfering agents, such as small interfering RNAs and ribozymes, to the appropriate cells in a way that is tissue/cell specific, efficient, and safe. Using human cytomegalovirus (HCMV) infection of differentiated macrophages as the model, we showed that Salmonella can efficiently deliver RNase P-based ribozyme sequence in specific human cells, leading to substantial ribozyme expression and effective inhibition of viral infection. We constructed a functional RNase P ribozyme (M1GS RNA) that targets the overlapping mRNA region of two HCMV capsid proteins, the capsid scaffolding protein (CSP) and assemblin, which are essential for viral capsid formation. Substantial expression of ribozymes was observed in human differentiated macrophages that were treated with attenuated Salmonella strains carrying the ribozyme sequence constructs. A reduction of 87-90% in viral CSP expression and a reduction of about 5,000-fold in viral growth were observed in cells that were treated with Salmonella carrying the sequence of the functional ribozyme but not with those carrying the sequence of a control ribozyme that contained mutations abolishing the catalytic activity. To our knowledge, this study showed for the first time that ribozymes expressed following targeted gene transfer with Salmonella-based vectors are highly active and specific in blocking viral infection. Moreover, these results demonstrate the feasibility to develop Salmonella-mediated gene transfer of RNase P ribozymes as an effective approach for gene-targeting applications. PMID- 20360565 TI - Concerted O atom-proton transfer in the O-O bond forming step in water oxidation. AB - As the terminal step in photosystem II, and a potential half-reaction for artificial photosynthesis, water oxidation (2H(2)O --> O(2) + 4e(-) + 4H(+)) is key, but it imposes a significant mechanistic challenge with requirements for both 4e(-)/4H(+) loss and O-O bond formation. Significant progress in water oxidation catalysis has been achieved recently by use of single-site Ru metal complex catalysts such as [Ru(Mebimpy)(bpy)(OH(2))](2+) [Mebimpy = 2,6-bis(1 methylbenzimidazol-2-yl)pyridine; bpy = 2,2'-bipyridine]. When oxidized from to Ru(V) = O(3+), these complexes undergo O-O bond formation by O-atom attack on a H(2)O molecule, which is often the rate-limiting step. Microscopic details of O-O bond formation have been explored by quantum mechanical/molecular mechanical (QM/MM) simulations the results of which provide detailed insight into mechanism and a strategy for enhancing catalytic rates. It utilizes added bases as proton acceptors and concerted atom-proton transfer (APT) with O-atom transfer to the O atom of a water molecule in concert with proton transfer to the base (B). Base catalyzed APT reactivity in water oxidation is observed both in solution and on the surfaces of oxide electrodes derivatized by attached phosphonated metal complex catalysts. These results have important implications for catalytic, electrocatalytic, and photoelectrocatalytic water oxidation. PMID- 20360566 TI - A moral life after a suicide death in Taiwan. AB - In this article we present the findings of a qualitative study exploring what suicide survivors in Taiwan experienced after a family member's suicide and how they adjusted to the perceived stigma. Fifteen suicide survivors participated in this study. We found that when a family member's suicide death occurred, survivors first kept a low profile when holding the funeral, and then tried to expel the dead person from their family. They also wished that their grief and painful, shameful feelings could be buried with the dead person. These findings suggest that health care professionals need to work more closely with suicide survivors through understanding the survivors' fear and pain from a sociocultural perspective, and to help them construct a new moral life. PMID- 20360567 TI - Traumatic brain injury, participation, and rural identity. AB - In this article we focus on participation following traumatic brain injury (TBI) in rural and regional Australian contexts, asking how aspects of rurality, such as place identity and rural belonging, impact on participation for the individual living with TBI. We found a preference for country living, despite disadvantages including distance from services and lack of anonymity. A rural identity provides access to an enabling narrative, the "rural idyll," which allows people with TBI to inhabit the realm of social normality. A rural identity is enabling in this regard, because it cooperates with TBI-based preferences for social isolation and a relaxed pace that accommodates fatigue. Thus, people living in rural areas report satisfaction with their quality of life despite restricted access to resources and reduced social participation. PMID- 20360568 TI - Connecting masculinity and depression among international male university students. AB - International university students can experience isolation amid academic pressures. Such circumstances can manifest as or exacerbate depression. This qualitative study involved 15 international male students at a Canadian university who were diagnosed or self-identified as having depression. Individual interviews revealed men's perspectives about causes, implications, and management of depression. Participants intertwined sex- and gender-based factors in detailing causes, and emphasized the potential for parents to impact depression. Implications of depression for embodying traditional masculine roles of breadwinner and career man influenced many men to filter details about their illness within "home" cultures. This practice often prevailed within Canada despite the men's perceptions that greater societal acceptance existed. Masculine ideals underpinned self-management strategies to fight depression and regain control. Counter to men's reluctance to disclose illness details were participants' self-management preference for peer-based support. Study findings highlight how masculine ideals and cultural constructs can influence depression experiences and expressions. PMID- 20360570 TI - Clinical and economic considerations in the use of inhaled anesthesia from the perspective of health-system pharmacists and anesthesiologists. Introduction. PMID- 20360569 TI - An anesthesiologist's perspective on inhaled anesthesia decision-making. AB - PURPOSE: To describe the culture and content of anesthesia practice; the stages, types, and goals of anesthesia; nomenclature and factors that can affect dosing of inhaled anesthesia; basis for anesthesiologist choices among inhaled anesthesia agents; and special considerations in using inhaled anesthesia in bariatric surgery patients, pediatric patients, and cardiac surgery patients; and to provide insights into myths associated with inhaled anesthesia. SUMMARY: The practice of anesthesiology requires complex monitoring, detailed knowledge of pharmacology, and the ability to make quick decisions about patient management. Four stages of anesthesia have been characterized on the basis of patient responsiveness to surgical stimuli. The second stage ("excitement") occurs during induction of or emergence from anesthesia; patients in this stage are particularly vulnerable to problems with laryngospasm, airway obstruction, uncontrolled motor movements, regurgitation, vomiting, and aspiration. In the United States, most general anesthesia involves inhaled agents. The minimum alveolar concentration (MAC) of inhaled anesthetic agents, which anesthesiologists use in dosing these drugs, can be affected by age, a variety of medications, and other patient-specific factors. MAC can be thought of as a measure of drug potency. Both MAC and solubility in blood and tissues differ among inhaled anesthetic agents. Agents with low solubility have a rapid onset and offset of effect and may allow for faster recovery. The choice among inhaled anesthetic agents may depend on their solubility, as well as the propensity to cause airway irritation and coughing, drug cost, and characteristics such as patient age, obesity, and duration of surgery. Anesthesia care providers' experience and habits may also influence drug choice. Emergence delirium (i.e., agitation) can occur with all three inhaled anesthetic agents in common use (isoflurane, desflurane, and sevoflurane). Other potential issues such as hepatotoxicity and nephrotoxicity are of minimal concern with these agents. Using low flow rates of fresh gas is one strategy for minimizing inhaled anesthesia costs, but it is not always feasible. CONCLUSION: Experience and careful consideration of the characteristics of inhaled anesthesia agents and surgery- and patient-specific factors allow anesthesia care providers to meet the rapidly changing needs of patients receiving inhaled anesthesia in a safe and cost effective manner. PMID- 20360572 TI - Managing inhaled anesthesia: challenges from a health-system pharmacist's perspective. AB - PURPOSE: To discuss the challenges that health-system pharmacists face in managing the use and costs of inhaled anesthesia in the operating room (OR), the characteristics of inhaled anesthesia agents, systems for delivering inhaled anesthesia, and the role of inhaled anesthetics in fast-track recovery after surgery. SUMMARY: Inhaled anesthetic agents are the most common drugs used in general anesthesia and are a substantial part of the anesthetic drug budget in health systems. Challenges for health-system pharmacists in managing costs associated with these agents include the lack of a dedicated OR pharmacy, limited access to the OR, unfamiliarity with some of the medications used in the OR, and difficulty quantifying inhaled anesthetic drug use. The three inhaled anesthesia agents currently used in the United States have proven to be safe and effective. These agents have differences in solubility in blood and tissues, which affect onset, absorption, and excretion. Isoflurane has the highest solubility in blood and tissues, which may result in slower recovery. Lower solubility allows for a faster recovery. The two newest agents on the market, sevoflurane and desflurane, both have low solubility, with desflurane having lower solubility than sevoflurane. Sevoflurane has the advantage of low pungency and is not associated with respiratory irritation. As a cost-savings initiative, the inhalation agents may be used with low flow rates, which minimizes the amount of inhaled anesthetic used. In addition, using the less soluble inhaled anesthetic agents as part of a fast-track approach will accelerate recovery by reducing time to emergence and recovery. This approach can potentially reduce costs to the institution. CONCLUSION: Understanding the differences in characteristics and delivery of the inhaled anesthesia agents will enable health-system pharmacists to collaborate with anesthesia care providers to better manage the use and costs of these agents. PMID- 20360573 TI - Economic considerations in the use of inhaled anesthetic agents. AB - PURPOSE: To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. SUMMARY: Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. CONCLUSION: Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings. PMID- 20360574 TI - ASHP professional policy recommendations--Invitation to comment. PMID- 20360575 TI - New direct thrombin inhibitor becomes available. PMID- 20360576 TI - Defense Department sees results on outcomes research. PMID- 20360577 TI - Hospital pharmacists' job stability improves, survey finds: Quarter of workweek spent on patient care activities. PMID- 20360578 TI - Engaging patients in care poses challenges. PMID- 20360579 TI - Effect of interprofessional education in an outpatient clinic on patient care and professional relationships. PMID- 20360580 TI - Hazards of concomitant administration of methotrexate and glutamine. PMID- 20360582 TI - Lack of clear statement and outrage from ASHP on Cropp case. PMID- 20360583 TI - Alert fatigue: A lesson relearned. PMID- 20360584 TI - Evidence for interaction between clopidogrel and proton-pump inhibitors. PMID- 20360587 TI - Pharmacy-nursing intervention to improve accuracy and completeness of medication histories. PMID- 20360588 TI - Effects of an adverse-drug-event alert system on cost and quality outcomes in community hospitals. AB - PURPOSE: The effects of an adverse-drug-event (ADE) alert system on cost and quality outcomes in community hospitals were evaluated. METHODS: This retrospective observational study evaluated the effects of an ADE alert system in seven hospitals in the Trinity Health network. Outcomes for all inpatients admitted to these hospitals after and one year before the deployment of an ADE alert system were evaluated. Inpatients in two network hospitals that lacked any computerized ADE alert system constituted the external control group. Administrative data were gathered for patients from these facilities for the same time frames as for the preimplementation and postimplementation groups. Primary outcomes evaluated included pharmacy department costs, variable drug costs, and mortality rates. Secondary outcomes included total hospitalization costs, length of hospital stay (LOS), rate of readmission, and case-mix index. Mean differences in primary and secondary outcome measures across all four groups were examined using analysis of variance. RESULTS: Significant decreases in mean pharmacy department costs per patient were observed from preimplementation to postimplementation (p < 0.001), while pharmacy department costs increased significantly in the external control group (p = 0.029). Drug costs decreased significantly from baseline (p < 0.001) in the postimplementation group. Drug costs increased significantly in the external control group (p = 0.029). Severity adjusted mortality rates and LOS decreased significantly in the postimplementation group. Total patient hospitalization costs, both crude and severity adjusted, significantly increased in both groups. CONCLUSION: Implementation of an ADE alert system in seven community hospitals demonstrated significant decreases in pharmacy department costs, variable drug costs, and severity-adjusted mortality rates. PMID- 20360589 TI - Implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital. AB - PURPOSE: The development and implementation of an extended-infusion piperacillin tazobactam program at an urban teaching hospital are described. SUMMARY: A multidisciplinary team was formed to address the feasibility of converting from the standard 30-minute infusion to an extended infusion of piperacillin- tazobactam. Before hospitalwide implementation, feasibility studies were performed in a subset of patients to identify potential barriers to program implementation. On the day of hospitalwide conversion, the orderables for piperacillin-tazobactam were reprogrammed in the computerized prescriber-order entry system to allow separate options for the 30-minute infusion (for pediatric patients) and the extended-infusion regimen. After selecting the orderable for the extended-infusion regimen, an electronic message appeared to remind prescribers of the rationale for this change and recommended indications for piperacillin-tazobactam. Program success was prospectively evaluated on 11 weekdays after hospitalwide conversion for all 96 adult inpatients receiving piperacillin-tazobactam. Of the 194 piperacillin-tazobactam doses observed, 90% were appropriate, with compliance increasing to 100% by the end of the observation period. There was near-complete cessation of the every-6-hour dosage interval and a marked increase in the every-8-hour and every-12-hour dosage intervals. The number of piperacillin-tazobactam doses per 1000 patient-days significantly decreased during the postimplementation period. During the postimplementation period, pharmacy expenditures related to piperacillin tazobactam decreased by 18% and the total number of grams of piperacillin tazobactam purchased decreased by 24%. CONCLUSION: A hospitalwide program for the administration of extended-infusion piperacillin-tazobactam was safely and successfully implemented using a multi-disciplinary approach in an urban teaching hospital. PMID- 20360590 TI - ASHP guidelines on remote medication order processing. PMID- 20360591 TI - Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation. AB - The prevalence of cerebral palsy (CP) shows little temporal or geographic variation and is associated with preterm birth, maternal/fetal infection/inflammation, and fetal growth restriction (IUGR), a potential surrogate for chronic fetal hypoxemia (CHX). We previously demonstrated CHX causes a fetal inflammatory response syndrome (FIRS). Herein, we test the hypothesis that CHX may cause fetal brain injury by upregulating inflammatory cytokine cascades, culminating in apoptosis pathway activation. Time-mated guinea pigs were housed in 12% or 10.5% O(2) for the last 21% of gestation. Chronic fetal hypoxemia increased the lactate/pyruvate and decreased the glutathione (GSH)/oxidized glutathione (GSSH) ratios, confirming a shift to a prooxidant state. The end result was a >30% decrease in hippocampal neuron density. Based on a microarray spotted with 113 cytokines and receptors, 22 genes were upregulated by CHX in proportion to the degree of hypoxia; the findings were confirmed by quantitative polymerase chain reaction (PCR). Thus, CHX triggers fetal brain inflammation inversely proportional to its severity characterized by increased apoptosis and neuronal loss. We suggest CHX fetal brain injury is not directly caused by oxygen deprivation but rather is an adaptive response that becomes maladaptive. PMID- 20360592 TI - The effect of intrauterine growth restriction on circulating surfactant protein D concentrations in the perinatal period. AB - The aim of this study was to investigate possible alterations in circulating concentrations of surfactant protein D (SP-D)-an important component of the innate immune system that is upregulated in pulmonary diseases-in appropriate for gestational age (AGA) and intrauterine growth-restricted (IUGR) pregnancies, because the latter are characterized by structural lung immaturity, impaired immunocompetence, and increased risk of respiratory infections and chronic obstructive lung disease in later life. Serum SP-D concentrations were determined in 40 mothers and their 20 IUGR and 20 AGA full-term fetuses-neonates on postnatal day 1 (N1) and 4 (N4). Fetal SP-D concentrations were higher in the IUGR group (b = 18.16, 95% CI: 6.86-29.47, P = .002) and negatively correlated with infants' customized centiles and gestational age (r = -.326, P = .04, and r = -.446, P = .004, respectively). In both groups, fetal SP-D concentrations were lower than N1 and N4 ones (P .05) among the 4 groups in displacement after cyclical loading or load at 2 mm of displacement. CONCLUSION: Both knotless and simple anchor configurations demonstrated similar single loads to failure (without cycling); however, the knotless device required less single load to displace 2 mm. All repair stitches, including simple, horizontal, and double loaded performed similarly. CLINICAL RELEVANCE: The findings may suggest that with cyclical loading up to 25 N there is no difference in gapping greater than 2mm, but a macrotraumatic event may demonstrate a difference in fixation during the initial postoperative period. Additional in vivo studies are needed to determine whether these differences affect the integrity of the repair construct and, ultimately, the clinical outcome. PMID- 20360605 TI - Effect of electron beam irradiation on biomechanical properties of patellar tendon allografts in anterior cruciate ligament reconstruction. AB - BACKGROUND: Sterilization of anterior cruciate ligament (ACL) allografts is an important prerequisite to prevent disease transmission. However, mechanical tissue properties are compromised by most current sterilization procedures, so that uncompromised sterilization of allografts is difficult to achieve. Hypothesis/ PURPOSE: The aim of this study was to evaluate the effect of the novel electron beam sterilization procedure on the biomechanical properties of human patellar tendon allografts at various irradiation dosages. Electron beam sterilization may be an appropriate alternative to gamma sterilization. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-two human 10-mm wide bone patellar tendon-bone grafts were randomized into 4 groups of sterilization with 15, 25, or 34 kGy of electron beam irradiation, respectively. The grafts' biomechanical properties were evaluated at time zero. Unsterilized grafts functioned as controls. Biomechanical properties were analyzed during cyclic and load-to-failure testing. RESULTS: Strain and cyclic elongation response showed no significant differences between the groups. Electron beam irradiation had no significant effect on stiffness and failure load with the exception of 34 kGy, which resulted in a significant decrease in failure load (1300.6 +/- 229.2 N) compared with unsterilized grafts (1630.5 +/- 331.1 N). CONCLUSION: This study showed that electron beam might be an appropriate alternative in sterilization of patellar tendon allografts with minimal effect on mechanical properties of tendon grafts in vitro. Future studies will have to evaluate the effect of the process on the biological properties of allografts in vitro and in vivo. CLINICAL RELEVANCE: Terminal sterilization of patellar tendon allografts with electron beam irradiation can ensure higher safety of transplanted grafts and hence improve patient safety and acceptance. PMID- 20360606 TI - Dynamic radiologic evaluation of horizontal instability in acute acromioclavicular joint dislocations. AB - BACKGROUND: Biplane radiologic evaluation is indispensable for the correct diagnosis of acute acromioclavicular (AC) joint injuries. Thus far, no functional radiographic techniques have been quantified to evaluate horizontal instability in acute AC joint dislocations. HYPOTHESIS: Supine dynamic axillary lateral shoulder views detect horizontal instability of the distal clavicle in patients with acute AC joint dislocations. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: Twenty-five consecutive patients with a mean age of 39 +/- 14 years with acute AC joint injury underwent biplane radiologic evaluation, including a conventional Zanca view and an axillary lateral view in a sitting position. In addition, supine axillary lateral views with the arm in 90 degrees of abduction and 60 degrees of flexion and extension were taken to evaluate the horizontal dynamics of the distal clavicle. The gleno-acromio-clavicular angle (GACA) was introduced and used to quantify the horizontal clavicular dynamics in terms of angle differences. The unaffected shoulders served as the control group. RESULTS: Superior dislocation of the lateral clavicle in the Zanca view was classified as Rockwood type II in 7 patients, type III in 15, and type V in 3. The axillary lateral view in a sitting position showed posterior dislocation of the distal clavicle in 8 patients (Rockwood type IV injury). Dynamic radiologic evaluation revealed an average GACA difference between the neutral and anterior position of the arm of 7.1 degrees +/- 5.5 degrees for the unaffected shoulder. In the injured AC joints, 11 patients showed no radiologic evidence of horizontal instability (group A) with a GACA difference of 7.1 degrees +/- 4.8 degrees . Increased anteroposterior translation was evident in 14 patients (group B) with a GACA difference of 30.3 degrees +/- 14.3 degrees (P < .001). CONCLUSION: Functional axillary radiologic evaluation seems to represent a simple imaging tool to reveal dynamic horizontal instability. CLINICAL RELEVANCE: Horizontal instability of the distal clavicle in acute AC joint injuries represents an indication for surgical treatment. Dynamic axillary radiologic evaluation may detect previously missed unstable injuries. This evaluation might be relevant when deciding on surgical AC joint stabilization. PMID- 20360607 TI - Two- to 4-year follow-up to a comparison of home versus physical therapy supervised rehabilitation programs after anterior cruciate ligament reconstruction. AB - BACKGROUND: There have been no long-term follow-up studies comparing a predominantly home-based rehabilitation program with a standard physical therapy program after anterior cruciate ligament (ACL) reconstruction. Demonstrating the long-term success of such a cost-effective program would be beneficial to guide future rehabilitation practice. PURPOSE: To determine whether there were any differences in long-term outcome between recreational athletes who performed a physical therapy-supervised rehabilitation program and those who performed a primarily home-based rehabilitation program in the first 3 months after ACL reconstruction. STUDY DESIGN: Randomized clinical trial; Level of evidence, 1. METHODS: Patients were randomized before ACL reconstruction surgery to either the physical therapy-supervised (17 physical therapy sessions) or home-based (4 physical therapy sessions) program. Eighty-eight of the original 129 patients returned 2 to 4 years after surgery to assess their long-term clinical outcomes. Primary outcome was the ACL quality of life questionnaire (ACL QOL). Secondary outcomes were bilateral difference in knee extension and flexion range of motion, sagittal plane knee laxity, relative quadriceps and hamstring strength, and objective International Knee Documentation Committee score. Unpaired t tests and a chi-square test were used for the comparisons. RESULTS: The home-based group had a significantly higher mean ACL QOL score (80.0 +/- 16.2) than the physical therapy-supervised group (69.9 +/- 22.0) a mean of 38 months after surgery (P = .02, 95% confidence interval [CI]: 1.7, 18.4). The mean change in ACL QOL score from before surgery to follow-up was not significantly different between the groups (physical therapy = 40.0, home = 45.8, P = .26, 95% CI: -15.8, 4.4). There were no significant differences in the secondary outcome measures. CONCLUSION: This long-term study upholds the short-term findings of the original randomized clinical trial by demonstrating that patients who participate in a predominantly home-based rehabilitation program in the first 3 months after ACL reconstruction have similar 2- to 4-year outcomes compared with those patients who participate in a more clinically supervised program. PMID- 20360608 TI - Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study. AB - BACKGROUND: Several methods are used to treat focal chondral and osteochondral defects on the weightbearing surfaces of synovial joints. Autologous osteochondral grafting is 1 option used to replace hyaline cartilage in the defect. HYPOTHESIS: Mosaicplasty is effective in returning elite athletes to participation in sports. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In 3 institutes, 354 of 383 patients were followed from 2 to 17 years (average, 9.6 years). The results of mosaicplasty were prospectively evaluated at 6 weeks, 3 months, 6 months, and yearly with patient-reported outcomes measures and radiographs. RESULTS: Slight or moderate degenerative changes (Fairbank grade I or II) were detected preoperatively in 27% of the cases and in 36% of the cases at follow-up. Fairbank grade III changes were observed in 5 cases. An average radiographic deterioration of 0.32 on the Fairbank scale was detected (preoperative, 0.34; postoperative, 0.66). Good to excellent results were found in 91% of femoral mosaicplasties, 86% of tibial, and 74% of patellofemoral; 92% of talar mosaicplasties had similar results (Hannover ankle scoring system). Patellofemoral pain related to graft harvest was observed in 5% of cases. Second look arthroscopies revealed good, congruent, gliding surfaces of the transplants and acceptable fibrocartilage coverage of donor sites in 16 patients and degenerative changes of the transplants in 5 cases. Histological evaluation revealed good graft incorporation in all 11 cases. Two infections and 3 deep venous thromboses occurred. CONCLUSION: Despite a higher rate of preoperative osteoarthritic changes in the athletic patients, clinical outcomes of mosaicplasty in this group demonstrated a success rate similar to that of less athletic patients. Higher motivation resulted in better subjective evaluation. Slight deterioration in results occurred during the 9.6-year follow-up; thus, autologous osteochondral mosaicplasty may be a useful alternative for the treatment of 1.0- to 4.0-cm(2) focal chondral and osteochondral lesions in competitive athletes. PMID- 20360609 TI - Regulation of single-stranded DNA binding by the C termini of Escherichia coli single-stranded DNA-binding (SSB) protein. AB - The homotetrameric Escherichia coli single-stranded DNA-binding (SSB) protein plays a central role in DNA replication, repair, and recombination. In addition to its essential activity of binding to transiently formed single-stranded (ss) DNA, SSB also binds an array of partner proteins and recruits them to their sites of action using its four intrinsically disordered C-terminal tails. Here we show that the binding of ssDNA to SSB is inhibited by the SSB C-terminal tails, specifically by the last 8 highly acidic amino acids that comprise the binding site for its multiple partner proteins. We examined the energetics of ssDNA binding to short oligodeoxynucleotides and find that at moderate salt concentration, removal of the acidic C-terminal ends increases the intrinsic affinity for ssDNA and enhances the negative cooperativity between ssDNA binding sites, indicating that the C termini exert an inhibitory effect on ssDNA binding. This inhibitory effect decreases as the salt concentration increases. Binding of ssDNA to approximately half of the SSB subunits relieves the inhibitory effect for all of the subunits. The inhibition by the C termini is due primarily to a less favorable entropy change upon ssDNA binding. These observations explain why ssDNA binding to SSB enhances the affinity of SSB for its partner proteins and suggest that the C termini of SSB may interact, at least transiently, with its ssDNA binding sites. This inhibition and its relief by ssDNA binding suggest a mechanism that enhances the ability of SSB to selectively recruit its partner proteins to sites on DNA. PMID- 20360610 TI - EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival, cell invasion, focal adhesions, and mammalian target of rapamycin activation. AB - Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130(Cas). Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130(Cas). WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted. PMID- 20360611 TI - Huntington's disease: pathogenesis to animal models. AB - Huntington's disease (HD) is an inherited genetic disorder, characterized by cognitive dysfunction and abnormal body movements called chorea. George Huntington, an Ohio physician, described the disease precisely in 1872. HD is a dominantly inherited disorder, characterized by progressive neurodegeneration of the striatum but also involves other regions, primarily the cerebral cortex. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding the huntingtin protein. Various hypotheses have been put forward to explain the pathogenic mechanisms of mutant huntingtin-induced neuronal dysfunction and cell death. None of these hypotheses, however, offers a clear explanation; thus, it remains a topic of research interest. HD is considered to be an important disease, embodying many of the major themes in modern neuroscience, including molecular genetics, selective neuronal vulnerability, excitotoxicity, mitochondrial dysfunction, apoptosis and transcriptional dysregulation. A number of recent reports have concluded that oxidative stress plays a key role in HD pathogenesis. Although there is no specific treatment available to block disease progression, treatments are available to help in controlling the chorea symptoms. As animal models are the best tools to evaluate any therapeutic agent, there are also different animal models available, mimicking a few or a larger number of symptoms. Each model has its own advantages and limitations. The present review deals with the pathophysiology and various cascades contributing to HD pathogenesis and progression as well as drug targets, such as dopaminergic, gamma amino butyric acid (GABA)ergic, glutamate adenosine receptor, peptidergic pathways, cannabinoid receptor, and adjuvant therapeutic drug targets such as oxidative stress and mitochondrial dysfunction that can be targeted for future experimental study. The present review also focuses on the animal models (behavioral and genetic) used to unravel pathogenetic mechanisms and the identification of novel drug targets. PMID- 20360612 TI - Liver X receptor (LXR) and the reproductive system--a potential novel target for therapeutic intervention. AB - Liver X receptor (LXR) alpha and beta are ligand-activated transcription factors that regulate the expression of genes involved in the removal of cholesterol from cells by high-density lipoproteins, the transport of cholesterol to the liver and the biliary excretion of cholesterol. LXRs are activated by oxygenated cholesterol derivatives such as 24(S),25-epoxycholesterol or 24(S)-, 25- and 27 hydroxycholesterol. In this review, we will discuss the role of LXR in the reproductive system and perspectives on the application of LXR agonists in the treatment of reproductive pathologies. Interestingly, progressive age-related impairment of fertility is observed in both female and male LXR knockout mice. Reduced fertility in female LXR knockout mice is associated with resistance to follicular fluid meiosis-activating sterol (FF-MAS), the intermediate of cholesterol synthesis generated in the ovaries that is responsible for stimulating oocyte meiosis partially in a LXR-dependent manner. Female mice lacking both LXR isoforms exhibit symptoms of ovarian hyperstimulation syndrome when treated with pharmacological doses of gonadotropins. LXR agonists have mainly been considered as potential anti-atherosclerotic medications. However, experimental studies suggest that natural or synthetic LXR agonists may also effectively treat some reproductive pathologies, such as infertility, impaired uterine contractility, hormone-dependent cancers and insulin resistance in patients with polycystic ovarian syndrome. However, the specific adverse effects of LXR agonists on the reproductive system must also be considered. Adverse effects of LXR agonists include impaired trophoblast invasion, excessive transplacental cholesterol transport from the mother to the fetus leading to fetal hypercholesterolemia, and augmented estrogen deficiency after menopause. PMID- 20360613 TI - Role of endothelin-1 receptor blockers on hemodynamic parameters and oxidative stress. AB - Endothelin (ET) was first isolated and described by Yanagisawa et al. and has since been described as one of the most potent known vasoconstrictor compounds. ET-1 mediates its effects via two types of receptors, ETA and ETB, which are expressed in the vascular smooth muscle cells, endothelial cells, intestines and brain. Secretion of ET-1 results in long-lasting vasoconstriction, increased blood pressure and, in turn, overproduction of free radicals. As dysregulation of the endothelin system is an important factor in the pathogenesis of several diseases including atherosclerosis, hypertension and endotoxic shock, the ETA and ETB receptors are attractive therapeutic targets for treatment of these disorders. The biosynthesis and release of ET-1 are regulated at the transcriptional level. Studies have shown that p38MAP kinase, nuclear factor kappaB (NF-kappaB), PKC/ERK and JNK/c-Jun all take part in the ROS-activated production of ET-1. Furthermore, administration of ET(A) significantly reduces the generation of free radicals. However, treatment with ETB receptor blockers does not elicit the same effect. Therefore, the effects of endothelin receptor blockers on blood pressure and the generation of free radicals remain debatable. This review summarizes recent investigations into the role of endothelin receptor blockers with respect to the modulation of hemodynamic parameters and the generation of free radicals. PMID- 20360614 TI - 9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease. AB - In a previous study, a primary culture of midbrain cells was exposed to 9-methyl beta-carboline for 48 h, which caused an increase in the number of tyrosine hydroxylase-positive cells. Quantitative RT-PCR revealed increased transcription of genes participating in the maturation of dopaminergic neurons. These in vitro findings prompted us to investigate the restorative actions of 9-methyl-beta carboline in vivo. The compound was delivered for 14 days into the left cerebral ventricle of rats pretreated with the neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP+) for 28 days applying a dose which lowered dopamine by approximately 50%. Interestingly, 9-methyl-beta-carboline reversed the dopamine-lowering effect of the neurotoxin in the left striatum. Stereological counts of tyrosine hydroxylase immunoreactive cells in the substantia nigra revealed that the neurotoxin caused a decrease in the number of those cells. However, when treated subsequently with 9-methyl-beta-carboline, the number reached normal values. In search of an explanation for the restorative activity, we analyzed the complexes that compose the respiratory chain in striatal mitochondria by 2-dimension gel electrophoresis followed by MALDI-TOF peptide mass fingerprinting.We found no changes in the overall composition of the complexes. However, the activity of complex I was increased by approximately 80% in mitochondria from rats treated with MPP+ and 9 methyl-beta-carboline compared to MPP+ and saline and to sham-operated rats, as determined by measurements of nicotinamide adenine dinucleotide dehydrogenase activity. Microarray technology and single RT-PCR revealed the induction of neurotrophins: brain-derived neurotrophic factor, conserved dopamine neurotrophic factor, cerebellin 1 precursor protein, and ciliary neurotrophic factor. Selected western blots yielded consistent results. The findings demonstrate restorative effects of 9-methyl-beta-carboline in an animal model of Parkinson's disease that improve the effectiveness of the respiratory chain and promote the transcription and expression of neurotrophin-related genes. PMID- 20360615 TI - Effects of blockade of central dopamine D1 and D2 receptors on thermoregulation, metabolic rate and running performance. AB - To assess the effects of a blockade of central D1- and D2-dopaminergic receptors on metabolic rate, heat balance and running performance, 10 nmol (2 microl) of a solution of the D(1) antagonist SCH-23390 hydrochloride (SCH, n = 6), D2 antagonist eticlopride hydrochloride (Eti, n = 6), or 2 microl of 0.15 M NaCl (SAL, n = 6) was injected intracerebroventricularly into Wistar rats before the animals began graded running until fatigue (starting at 10 m/min, increasing by 1 m/min increment every 3 min until fatigue, 5% inclination). Oxygen consumption and body temperature were recorded at rest, during exercise and following 30 min of recovery. Control experiments with injection of two doses (10 and 20 nmol/rat) of either SCH or Eti solution were carried out in resting rats as well. Body heating rate, heat storage, workload and mechanical efficiency were calculated. Although SCH and Eti treatments did not induce thermal effects in resting animals, they markedly reduced running performance (-83%, SCH; -59% Eti, p < 0.05) and decreased maximal oxygen uptake (-79%, SCH; -45%, Eti, p < 0.05) in running rats. In addition, these treatments induced a higher body heating rate and persistent hyperthermia during the recovery period. Our data demonstrate that the alteration in dopamine transmission induced by the central blockade of dopamine- D1 and D2 receptors impairs running performance by decreasing the tolerance to heat storage. This blockade also impairs the dissipation of exercise induced heat and metabolic rate recovery during the post-exercise period. Our results provide evidence that central activation of either dopamine- D1 or D2 receptors is essential for heat balance and exercise performance. PMID- 20360616 TI - Effects of 2-chloroadenosine on cortical epileptic afterdischarges in immature rats. AB - Adenosine may represent an endogenous anticonvulsant in the brain. This study focused on the possible anticonvulsant action of an adenosine agonist, 2 chloroadenosine, against cortical epileptic afterdischarges (ADs) in immature rats. Three age groups of rat pups with implanted electrodes were studied: 12-, 18- and 25-days-old. The compound, 2-chloroadenosine, was injected after the first successful stimulation at doses of 1, 4 or 10 mg/kg intraperitoneally, and stimulation at the same intensity was repeated three more times. Movements directly elicited by stimulation, as well as clonic seizures accompanying electroencephalography (EEG) ADs, were markedly suppressed in only the 18-day-old animals. The effects in the 12- and especially the 25-day-old rats were moderate. The duration of the ADs decreased in all three age groups with 2-chloroadenosine treatment, and the shortest AD duration was seen in the treated, 12-day-old rats. The AD suppression also lasted longer in this age group than it did in the older animals. After a brief suppression of the second AD, the treated, 25-day-old group exhibited a significant AD rebound during the third and fourth stimulations. Taken together, our data show that 2-chloroadenosine exhibits an anticonvulsant effect that is dose- and age-dependent. PMID- 20360617 TI - Synthesis and pharmacological evaluation of pyrrolidin-2-one derivatives as antiarrhythmic, antihypertensive and alpha-adrenolytic agents. AB - A series of novel arylpiperazines bearing a pyrrolidin-2-one fragment were synthesized and evaluated for their binding affinity for alpha1- and alpha2 adrenoceptors (ARs) as well as their antiarrhythmic and antihypertensive activities. The highest affinity for the alpha1-AR was displayed by 1-{3-[4-(2 chloro-phenyl)-piperazin-1-yl]-propyl}-pyrrolidin-2-one 7, which binds with a pKi = 7.13. The highest affinity for the alpha2-AR was shown by 1-{3-[4-(4-chloro phenyl)-piperazin-1-yl]-propyl}-pyrrolidin-2-one 18, which binds with a pKi = 7.29. Among the compounds tested, 1-{3-[4-(2-ethoxy-phenyl)-piperazin-1-yl] propyl}-pyrrolidin-2-one 13 had the highest prophylactic antiarrhythmic activity in epinephrine-induced arrhythmia in anesthetized rats. Its ED50 value was 1.0 mg/kg intravenously (iv). The compounds with a hydroxy group in the 4-position of the phenyl ring or two substituents such as fluorine atoms in the 2 and 4 positions of the phenyl ring significantly decreased systolic and diastolic pressure in normotensive anesthetized rats at a dose of 2.5 mg/ kg iv, and their hypotensive effects lasted for longer than an hour. PMID- 20360618 TI - Does nebivolol influence serum concentrations of proinflammatory cytokines in hypertensive (SHR) and normotensive (WKY) rats? AB - A growing body of evidence suggests that some drugs used in cardiovascular diseases may modulate the level of proinflammatory cytokines. In the present study we examined whether nebivolol, a third generation beta-adrenergic blocker, influences lipopolysaccharide (LPS)-induced serum concentrations of TNF-alpha, IL 1beta, and IL-6 in normotensive (WKY) and spontaneously hypertensive rats (SHR). Nebivolol (5 mg/kg and 10 mg/kg) or vehicle were administered by gavage once a day for 21 days. The drug (5 mg/kg and 10 mg/kg) did not modify LPS-stimulated serum concentrations of TNF-alpha, IL-1beta and IL-6 in normotensive or hypertensive rats and did not affect the total cholesterol and HDL cholesterol level. Nebivolol, at the dose of 10 mg/kg, significantly increased the triglyceride concentration in SHR only. The results were accompanied by a statistically significant decrease in systolic, diastolic and mean blood pressure after 21 days of both of the drug doses. In hypertensive and normotensive rats, nebivolol had a hypotensive activity and neutral effect on lipid profile. In our in vivo model, the immunomodulating effect of the drug was not significant and probably did not depend on hemodynamic action. PMID- 20360619 TI - Estrogen-induced relaxation of the rat tail artery is attenuated in rats with pulmonary hypertension. AB - The mechanisms involved in the effects of estrogen on arterial smooth muscle contractility are very complex and not fully clarified. Therefore, the aim of this paper was to examine the mechanisms of estrogen-induced relaxation of the rat tail artery and, specifically, how pulmonary hypertension affects this action. We used male rats and performed experiments on isolated tail arteries in a control group and a group with pulmonary hypertension (PAH) induced by monocrotaline (60 mg/kg b.w. ip). The pD2 value (-log EC50) of phenylephrine significantly decreased in the presence of 20 microM of 17beta-estradiol (5.4 +/- 0.13 vs. 4.9 +/- 0.12, p < 0.05, n = 6). Estrogen-induced relaxation of a phenylephrine-precontracted tail artery has two components: endothelium-dependent (ED) and endothelium-independent (EI). The estrogen effect was independent of ATP sensitive K+ channels, vasoactive prostanoids and nitric oxide. PAH augmented the maximal effect of phenylephrine on the tail artery contractility but did not affect estrogen-induced ED-relaxation. However, the EI component of relaxation induced by estrogen was completely abolished in tail arteries obtained from animals with pulmonary hypertension. Pulmonary hypertension affects the sensitivity of the rat tail artery to phenylephrine and estrogen, leading to impairment of EI mechanisms of relaxation. Further experiments are required to elucidate the molecular mechanisms of this phenomenon. PMID- 20360620 TI - Effects of statins on nitric oxide/cGMP signaling in human umbilical vein endothelial cells. AB - Human umbilical vein endothelial cells (HUVECs) were established as in vitro models for the modulation of endothelial function and cell viability by statins. Emphasis was placed on the biphasic effects of the drugs on nitric oxide (NO) bioavailability and cytotoxicity, as well as drug interference with the interaction of endothelial NO synthase (eNOS) with caveolin-1 (Cav-1). Incubation of HUVECs with fluvastatin, lovastatin or cerivastatin for 24 h caused an approximately 3-fold upregulation of eNOS expression that was associated with increased eNOS activity and accumulation of cGMP. Cerivastatin exhibited the highest potency with an EC50 of 13.8 +/- 2 nM after 24 h, while having no effect after only 30 min. The effects of statins on eNOS expression were similar in control and Cav-1 knockdown cells, but the increase in eNOS activity was less pronounced in Cav-1-deficient cells. Statin-triggered cytotoxicity occurred at approximately 10-fold higher drug concentrations (maximal toxicity at 1-10 microM), was sensitive to mevalonate, and was significantly enhanced in the presence of NG-nitro-L-arginine. The overexpression of eNOS induced by clinically relevant concentrations of statins may contribute to the beneficial vascular effects of the drugs in patients. Stimulation of NO synthesis and cytotoxicity appear to share a common initial mechanism but involve distinct downstream signaling cascades that exhibit differential sensitivity to HMG-CoA reductase inhibition. PMID- 20360621 TI - Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats. AB - In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound. PMID- 20360622 TI - Metabolic and monocyte-suppressing actions of fenofibrate in patients with mixed dyslipidemia and early glucose metabolism disturbances. AB - The aim of this study was to compare the action of fenofibrate on monocyte cytokine release between patients with isolated mixed dyslipidemia and dyslipidemia coexisting with prediabetic states in relationship with its metabolic actions.We compared 96 primary mixed dyslipidemic patients and 29 age-, sex- and weight-matched control subjects with normal lipid profile. Depending on glucose metabolism, dyslipidemic patients were allocated into one of three treatment groups: isolated dyslipidemia, dyslipidemia coexisting with impaired fasting glucose (IFG) and dyslipidemia coexisting with impaired glucose tolerance (IGT). Lipid profile, fasting and 2-h post-glucose load plasma glucose levels, HOMA and monocyte release of interleukin-1beta and MCP-1 were assessed at baseline and after 30 and 90 days of micronized fenofibrate treatment (267 mg/daily). Compared to monocytes from control subjects, monocytes of dyslipidemic patients released a greater amounts of interleukin-1beta and MCP-1. MCP-1 release was higher in the IFG group than in the remaining groups of dyslipidemic patients. In all groups of dyslipidemic patients, micronized fenofibrate reduced monocyte release of interleukin-1beta and MCP-1, and this effect was stronger in prediabetic subjects. Fenofibrate treatment also decreased HOMA in IFG and IGT patients, fasting plasma glucose in IFG subjects and 2-h post-glucose load plasma glucose in IGT patients. The observed differences between the studied groups regarding fenofibrate action on glucose homeostasis and cytokine release suggest that fibrate therapy may bring particular benefits to persons with metabolic syndrome. PMID- 20360623 TI - N-acetylcysteine inhibits IL-8 and MMP-9 release and ICAM-1 expression by bronchoalveolar cells from interstitial lung disease patients. AB - N-acetylcysteine (NAC), owing to its antioxidant, mucolytic and anti-inflammatory properties, is used in the treatment of various pulmonary disorders. However, the direct effects of NAC on bronchoalveolar lavage (BAL) cells from patients suffering from interstitial lung diseases have not yet been studied. Therefore, the aim of the present work was to evaluate the effect of NAC on interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) production as well as intercellular cell adhesion molecule-1 (ICAM-1) expression by BAL cells from interstitial lung diseases. The study was performed on BAL cells from nine patients with interstitial lung disease: four patients with idiopathic pulmonary fibrosis (IPF) and five patients with sarcoidosis. Cultured unstimulated BAL cells were treated with increasing doses of NAC (1-30 mM). Production of IL-8 and MMP-9 was evaluated by specific enzyme-linked immuno-sorbent assays and ICAM-1 expression was studied by immunohistochemistry. NAC exerted a dose-dependent inhibitory effect on IL-8 and MMP-9 release and ICAM- expression by BAL macrophages and lymphocytes from patients with IPF and sarcoidosis. In conclusion, NAC inhibits production of factors playing a key role in the etiopathogenesis of interstitial lung diseases, thus suggesting its possible therapeutic potency in the treatment of these disorders. PMID- 20360624 TI - Local pulmonary opioid network in patients with lung cancer: a putative modulator of respiratory function. AB - Recently, there has been growing interest in the opioid regulation of physiological respiratory function. However, evidence for a local opioid network that includes endogenous opioid peptides and their receptors is scarce. Tissue samples from patients with lung cancer were examined by immunohistochemistry to identify the components of the opioid network: beta-endorphin (END); its precursor, proopiomelanocortin (POMC); the key processing enzymes prohormone convertase 1 and 2; carboxypeptidase E; and END's corresponding opioid receptor, the mu-opioid receptor (MOR). Additionally, we tested pulmonary function parameters in a patient with advanced lung cancer after inhalation of nebulized morphine. Confocal immunofluorescence microscopy revealed that the opioid precursor POMC colocalizes with its active peptide END, key processing enzymes and MOR in alveolar macrophages, submucosal glands, cancerous cells, and pulmonary neuroendocrine cells within the bronchial epithelium. In addition, MOR was identified on sensory nerve endings within the bronchial epithelium. Furthermore, nebulized morphine improved pulmonary function parameters in advanced lung cancer. These findings provide evidence of a local opioid network in functionally important anatomical structures of the respiratory system; this network consists of all the machinery required for POMC processing into active peptides, such as END, and contains the receptors for END. Our findings indicate a need for further clinical trials to elucidate the modulatory function of peripheral endogenous opioids in the human lung. PMID- 20360625 TI - Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. AB - The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT 116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the degradation of inhibitor of kappaB-alpha (IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer. PMID- 20360626 TI - Fluvastatin increases tyrosinase synthesis induced by alpha-melanocyte stimulating hormone in B16F10 melanoma cells. AB - The aim of this study was to evaluate the effect of fluvastatin on the alpha melanocyte-stimulating hormone-mediated increase in tyrosinase activity in the melanoma B16F10 cell line and to establish whether Akt and extracellular signal regulated kinase (Erk) inhibition is involved in tyrosinase synthesis after fluvastatin administration. Fluvastatin modulates alpha-melanocyte-stimulating hormone induced melanogenesis by increasing tyrosinase mRNA production, as shown by real time PCR, or tyrosinase protein synthesis, as presented by western blot technique. The stimulatory effect of fluvastatin on melanogenesis was, in part, induced by modulation of cell proliferation (decreased melanoma cell proliferation in G2/M phase) and possibly decrease of Akt. These findings indicate that fluvastatin increases tyrosinase synthesis induced by alpha melanocyte-stimulating hormone in B16F10 cells and reveal an unknown effect of statin use: their influence on melanin production. PMID- 20360627 TI - Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1. AB - Clinical trials with partial liquid ventilation demonstrate improvement in oxygenation, as well as some adverse side effects linked to the application of liquid perfluorocarbons (PFCs) during liquid ventilation. Thus, we examined the effects of systemic administration of PFC on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects on heme oxygenase-1 (HO-1), a compound that provides potent cytoprotection against lung injury. Rats were assigned to one of six groups (n = 8). Thirty minutes after they were challenged with LPS aerosol inhalation, perfluorohexane was given intraperitoneally every two hours. Ten hours after LPS inhalation, bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for enzyme linked immunosorbent assay, histologic, and Western-blot analyses. The results showed that perfluorohexane significantly decreased the wet to dry weight ratio, malondialdehyde (MDA) production, and myeloperoxidase (MPO) activity in the lung tissue. Also, perfluorohexane reduced the total protein content and levels of tumor necrosis factor-alpha (TNF-alpha) but increased the levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the BALF, resulting in decreased pulmonary edema and the infiltration of neutrophils into the lung tissues of LPS-treated rats. Furthermore, perfluorohexane increased HO-1 protein production and stimulated HO-1 activity in the lung tissue. Pre-treatment with Zinc protoporphyrin IX, an inhibitor of HO-1, decreased the protective effects of perfluorohexane in rats. In summary, systemic perfluorohexane alleviates LPS-induced lung injury in rats, and HO-1 may be involved in the mechanism of this reduction. PMID- 20360628 TI - Strong antioxidant activity of carane derivatives. AB - Oxidants play a significant role in causing oxidative stress, which underlies the pathogenesis of inflammation and rheumatoid arthritis. The processes associated with inflammatory responses are complex and often involve reactive oxygen species. There are many mediators that initiate and amplify the inflammatory response such as histamine, serotonin and metabolic products of arachidonic acid (thromboxane, prostaglandins and leukotrienes). In the present study, we examined the antioxidant activity of carane derivatives--KP-23 and its optical isomers- that possess strong local anesthetic and anti-inflammatory activity. The antioxidant effects (expressed as Trolox Equivalent Antioxidants Capacity, TEAC) were observed for one of the optical isomers of carane, a derivative of propranolol--KP-23R. The relative scavenging effect (%R) of ABTS+ by KP-23S, KP 23R and standards measured at 30 min was the following, listed in decreasing order: tetracaine > KP-23S > KP-23R > procaine > lignocaine > benzocaine (99, 85, 80, 38, 21 and 20%, respectively, at a concentration of 10 mM). The IC50 values also show strong antioxidant properties of the investigated KP compounds (ranging between 11-18 mM) and tetracaine (6.2 mM) compared to other local anesthetics (129-348 mM). Moreover, monoterpene derivatives were more effective as antioxidants than propranolol diastereoisomers (280-528 mM). We found that carane derivatives, in contrast to propranolol diastereoisomers, serve as potent antioxidants by scavenging radicals. PMID- 20360629 TI - Scavenging and antioxidant potential of physiological taurine concentrations against different reactive oxygen/nitrogen species. AB - While several studies have been conducted on the antioxidant properties of the beta-amino acid taurine, these studies all used concentrations lower than what is found physiologically. This study investigates the scavenging and antioxidant properties of physiological taurine concentrations against different reactive species. No reactivity between taurine and hydrogen peroxide was found; however, taurine exhibited significant scavenging potential against peroxyl radical, nitric oxide, and superoxide donors. This study also evaluated if taurine was able to minimize the in vitro CuZn-superoxide dismutase damage (SOD) induced by peroxynitrite. Taurine prevented both the formation of nitrotyrosine adducts and the decrease in SOD activity caused by peroxynitrite. In addition, taurine prevented the ex vivo damage caused by tert-butyl hydroperoxide in rat liver slices. These experimental data show that taurine, at different physiological concentrations efficiently scavenges many reactive oxygen and nitrogen species. This finding supports the hypothesis that the antioxidant properties of taurine may be critical for the maintenance of cellular functions, and it suggests a more important function of taurine that requires further investigation. PMID- 20360630 TI - Effect of p-isopropoxyphenylsuccinimide monohydrate on the anticonvulsant action of carbamazepine, phenobarbital, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. AB - This study was designed to determine the effects of p-isopropoxyphenylsuccinimide monohydrate (IPPS) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. Results indicate that IPPS administered intraperitoneally (ip) at doses of 75 and 150 mg/kg significantly elevated the threshold for electroconvulsions in mice. IPPS at lower doses of 18.75 and 37.5 mg/kg had no impact on the threshold for electroconvulsions in mice. Moreover, 37.5 mg/kg IPPS significantly enhanced the anticonvulsant activity of phenytoin and valproate, but not that of carbamazepine or phenobarbital, in the maximal electroshock seizure test in mice. IPPS (18.75 mg/kg) had no impact on the antiseizure action of phenytoin and valproate against maximal electroshock-induced seizures in mice. Pharmacokinetic experiments revealed that IPPS did not alter total brain concentrations of phenytoin or valproate in mice. In conclusion, the enhanced anticonvulsant action of phenytoin and valproate by IPPS in the mouse maximal electroshock-induced seizure model and lack of pharmacokinetic interactions make the combinations of IPPS with phenytoin and valproate of pivotal importance for further experimental and clinical studies. The combinations of IPPS with carbamazepine and phenobarbital are neutral from a preclinical viewpoint. PMID- 20360631 TI - Experimental investigation of factors affecting the absolute recovery coefficients in iodine-124 PET lesion imaging. AB - The use of recovery coefficients (RCs) in (124)I PET lesion imaging is a simple method to correct the imaged activity concentration (AC) primarily for the partial-volume effect and, to a minor extent, for the prompt gamma coincidence effect. The aim of this phantom study was to experimentally investigate a number of various factors affecting the (124)I RCs. Three RC-based correction approaches were considered. These approaches differ with respect to the volume of interest (VOI) drawn, which determines the imaged AC and the RCs: a single voxel VOI containing the maximum value (maximum RC), a spherical VOI with a diameter of the scanner resolution (resolution RC) and a VOI equaling the physical object volume (isovolume RC). Measurements were performed using mainly a stand-alone PET scanner (EXACT HR(+)) and a latest-generation PET/CT scanner (BIOGRAPH mCT). The RCs were determined using a cylindrical phantom containing spheres or rotational ellipsoids and were derived from images acquired with a reference acquisition protocol. For each type of RC, the influence of the following factors on the RC was assessed: object shape, background activity spill in and iterative image reconstruction parameters. To evaluate the robustness of the RC-based correction approaches, the percentage deviation between RC-corrected and true ACs was determined from images acquired with a clinical acquisition protocol of different AC regimes. The observed results of the shape and spill-in effects were compared with simulation data derived from a convolution-based model. The study demonstrated that the shape effect was negligible and, therefore, was in agreement with theoretical expectations. In contradiction to the simulation results, the observed spill-in effect was unexpectedly small. To avoid variations in the determination of RCs due to reconstruction parameter changes, image reconstruction with a pixel length of about one-third or less of the scanner resolution and an OSEM 1 x 32 algorithm or one with somewhat higher number of effective iterations are recommended. Using the clinical acquisition protocol, the phantom study indicated that the resolution- or isovolume-based recovery correction approaches appeared to be more appropriate to recover the ACs from patient data; however, the application of the three RC-based correction approaches to small lesions containing low ACs was, in particular, associated with large underestimations. The phantom study had several limitations, which were discussed in detail. PMID- 20360632 TI - Added soft tissue contrast using signal attenuation and the fractal dimension for optical coherence tomography images of porcine arterial tissue. AB - Optical coherence tomography (OCT) images of left-descending coronary tissues harvested from three porcine specimens were acquired with a home-build swept source OCT setup. Despite the fact that OCT is capable of acquiring high resolution circumferential images of vessels, many distinct histological features of a vessel have comparable optical properties leading to poor contrast in OCT images. Two classification methods were tested in this report for the purpose of enhancing contrast between soft-tissue components of porcine coronary vessels. One method involved analyzing the attenuation of the OCT signal as a function of light penetration into the tissue. We demonstrated that by analyzing the signal attenuation in this manner we were able to differentiate two media sub-layers with different orientations of the smooth muscle cells. The other classification method used in our study was fractal analysis. Fractal analysis was implemented in a box-counting (fractal dimension) image-processing code and was used as a tool to differentiate and quantify variations in tissue texture at various locations in the OCT images. The calculated average fractal dimensions had different values in distinct regions of interest (ROI) within the imaged coronary samples. When compared to the results obtained by using the attenuation of the OCT signal, the method of fractal analysis demonstrated better classification potential for distinguishing amongst the tissue ROI. PMID- 20360633 TI - Temperature elevation in the fetus from electromagnetic exposure during magnetic resonance imaging. AB - This study computationally assessed the temperature elevations due to electromagnetic wave energy deposition during magnetic resonance imaging in non pregnant and pregnant woman models. We used a thermal model with thermoregulatory response of the human body for our calculations. We also considered the effect of blood temperature variation on body core temperature. In a thermal equilibrium state, the temperature elevations in the intrinsic tissues of the woman and fetal tissues were 0.85 and 0.61 degrees C, respectively, at a whole-body averaged specific absorption rate of 2.0 W kg(-1), which is the restriction value of the International Electrotechnical Commission for the normal operating mode. As predicted, these values are below the temperature elevation of 1.5 degrees C that is expected to be teratogenic. However, these values exceeded the recommended temperature elevation limit of 0.5 degrees C by the International Commission on Non-Ionizing Radiation Protection. We also assessed the irradiation time required for a temperature elevation of 0.5 degrees C at the aforementioned specific absorption rate. As a result, the calculated irradiation time was 40 min. PMID- 20360634 TI - Lung cancer and angiogenesis imaging using synchrotron radiation. AB - Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body. PMID- 20360635 TI - Perfusion measurements by micro-CT using prior image constrained compressed sensing (PICCS): initial phantom results. AB - Micro-CT scanning has become an accepted standard for anatomical imaging in small animal disease and genome mutation models. Concurrently, perfusion imaging via tracking contrast dynamics after injection of an iodinated contrast agent is a well-established tool for clinical CT scanners. However, perfusion imaging is not yet commercially available on the micro-CT platform due to limitations in both radiation dose and temporal resolution. Recent hardware developments in micro-CT scanners enable continuous imaging of a given volume through the use of a slip ring gantry. Now that dynamic CT imaging is feasible, data may be acquired to measure tissue perfusion using a micro-CT scanner (CT Imaging, Erlangen, Germany). However, rapid imaging using micro-CT scanners leads to high image noise in individual time frames. Using the standard filtered backprojection (FBP) image reconstruction, images are prohibitively noisy for calculation of voxel-by voxel perfusion maps. In this study, we apply prior image constrained compressed sensing (PICCS) to reconstruct images with significantly lower noise variance. In perfusion phantom experiments performed on a micro-CT scanner, the PICCS reconstruction enabled a reduction to 1/16 of the noise variance of standard FBP reconstruction, without compromising the spatial or temporal resolution. This enables a significant increase in dose efficiency, and thus, significantly less exposure time is needed to acquire images amenable to perfusion processing. This reduction in required irradiation time enables voxel-by-voxel perfusion maps to be generated on micro-CT scanners. Sample perfusion maps using a deconvolution based perfusion analysis are included to demonstrate the improvement in image quality using the PICCS algorithm. PMID- 20360636 TI - Attenuation correction for the large non-human primate brain imaging using microPET. AB - Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner. PMID- 20360637 TI - 5-HT modulation of pain in SI and SII revealed by fMRI. AB - OBJECTIVE: To observe the different cerebral activations between pre administration and post-administration of tryptophan-depleted amino acid mixture (TRP-)/balanced amino acid mixture (BAL) in healthy volunteers through functional magnetic resonance imaging (fMRI) when they received electrical stimulation at the same time. Furthermore, the effects of 5-hydroxytryptamine (5-HT) were explored in pain modulation network. METHODS: Two-phase crossover design was adopted. Six right-handed healthy volunteers participated in the experiment. TRP- and BAL were administered to each participant according to the Young's method. Volunteers were scanned under fMRI with or without administration of TRP- or BAL when receiving electrical stimulation simultaneously. Analysis of functional neuroimages (AFNI) software was used to show the different activations in the human brain between pre- and post-administration of TRP-/BAL. Then all the results were analyzed by SPSS 14.0. RESULTS: (1) Bilateral primary somatosensory cortex (SI) and secondary somatosensory cortex (SII) were activated during pre administration and post-administration of TRP-, but the activated volumes of bilateral SI and SII during post-administration of TRP- were found significantly larger than that during pre-administration of TRP (P<0.05). (2) All the activated regions showed no difference between pre- and post-administration of BAL. (3) There were significant differences of pain threshold between pre- and post administration of TRP- (P<0.01), which meant that pain threshold reduced remarkably after TRP- administration, while it showed no difference between pre- and post-administration of BAL (P>0.05). CONCLUSION: 5-HT plays an important role in pain modulation in the central nervous system, TRP- causes acute tryptophan depletion (ATD) through reducing the level of 5-HT in the human brain, which can induce the decrease of volunteers' pain threshold. The activated volumes of bilateral SI and SII display significant difference between pre- and post administration of TRP-, suggesting these brain areas may not only involve in the 5-HT related activities but in pain modulation network as well. PMID- 20360639 TI - Angiopoietin-like protein 3 and adiponectin levels in patients with metabolic syndrome. AB - OBJECTIVE: To investigate the changes of serum angiopoietin-like protein 3 (Angptl3) and adiponectin levels in patients with metabolic syndrome (MS) in order to understand their association with the MS. METHODS: Serum Angptl3 and adiponectin levels were measured by sandwich ELISA in a group of 111 patients with MS and 152 normal controls. RESULTS: Serum adiponectin was lower in the MS patients than in the control subjects [4.22(1.01-23.29) microg/mL vs. 5.41(0.97 22.27) microg/mL, P<0.05]. With regard to serum Angptl3, there was no significant difference between the 2 groups(P>0.05). Serum adiponectin was correlated to Angptl3 and high density lipoprotein-cholesterol (HDL-C)(P<0.001) and negatively correlated to body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), triglyceride (TG), fasting plasma glucose (FBG), fasting insulin (FINS) and homeostatic model assessment method-insulin resistance (HOMA-IR) (P<0.001). Serum Angptl3 was positively correlated with adiponectin (P<0.001). Serum adiponectin was found to be independently positive determinant for Angptl3 concentrations (b'=0.256, P<0.001). Adiponectin was inversely correlated with TG and HOMA-IR (b'=-0.234, -0.145, P<0.001). CONCLUSION: Adiponectin is decreased in MS patients and may be correlated to Angptl3. PMID- 20360638 TI - Employment-related anxiety and depression in senior college students in China. AB - OBJECTIVE: To examine the association of employment-related events with depression and anxiety in senior college students in China. METHODS: Altogether 1321 senior college students were recruited from Central South University and the survey was administered anonymously. Anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Employment-related events were reflected by the employment-related options when students were surveyed. Logistic regression was used to estimate the effect of employment-related events on anxiety and depression. RESULTS: We collected 1178 valid questionnaires. Taking 50 and 16 as the cutting-point of SAS and CES-D, we found 18.9% and 55.4% of the participants showed symptoms of anxiety and depression, respectively. After controlling confounding factors, those students who had taken the entrance exam of graduate schools and were optimistic for the result, those who had taken the entrance exam of graduate schools but were pessimistic for the result, and those who neither took the entrance exam of graduate schools nor received a job offer, had a higher risk of anxiety than those who would attend a graduate school without exam, and the odds ratios were 2.5, 2.3, and 3.5, respectively. For students' depression, the odds ratios of the three categories mentioned above were 2.0, 1.5, and 2.6, respectively. CONCLUSION: Senior college students who face bad employment-related events are at a higher risk of anxiety and depression. PMID- 20360640 TI - [Molecular mechanism of SH2B1 in regulating JAK2/IRS2 during obesity development]. AB - OBJECTIVE: In order to investigate the effect of SH2B1 on leptin signal transduction JAK2/IRS2 and its biological function. METHODS: Vitro kinase assay and Western blot were used to analyse tyrosine phosphorylatin of key molecule JAK2 and insulin receptor substrate-2 (IRS2). ELISA was used to measure the plasma leptin levels in mice. The postnatal growth of mice was monitored over 27 weeks. RESULTS: SH2B1 dramatically enhanced the leptin-stimulated tyrosine phosphorylation of JAK2 and IRS2 in HEK293 cells stably expressing LRb (HEK239(LRb)). Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of hyphothalamic IRS2 were significantly impaired in SH2B1(-/-) mice. The deletion of SH2B1 led to leptin resistance,and fasting and randomly fed plasma leptin levels were respectively 3.2 times and 5.1 times higher in SH2B1(-/ ) males than wild-type littermates at 15 weeks of age. SH2B1(-/-) males gained body weight rapidly and exceeded wild-type littermates from 5th week. SH2B1(-/-) (at 21 weeks) was approximately twice heavier than wild-type littermates. CONCLUSION: SH2B1 is an endogenous enhancer of leptin sensitivity and required for maintaining normal bodyweight in mice via leptin JAK2/IRS2 pathway. PMID- 20360641 TI - [PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes]. AB - OBJECTIVE: To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population. METHODS: We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients. RESULTS: No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005). CONCLUSION: A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD. PMID- 20360642 TI - [Effect of aldosterone and its antagonist spironolactone on epithelial mesenchymal transition of normal rat kidney epithelial cells in high glucose]. AB - OBJECTIVE: To determine the effect of aldosterone and its antagonist, spironolactone on epithelial-mesenchymal transition (EMT) of normal rat kidney epithelial cells (NRK-52E) in a high glucose milieu,and to explore the mechanism of renoprotection in diabetic nephropathy (DN ) in rats involving aldosterone and spironolacton. METHODS: NRK-52E cells were simultaneously cultured in the serum free Dulbecco's modification of Eagle's medium Dulbecco (DMEM) for 12 hours. Then the low glucose (LG) group was cultured in LG (1000 mg/L) DMEM:The high glucose (HG) group was cultured in high glucose (4,500 mg/L) DMEM. The aldosterone (Aldo) groups were cultured in high glucose DMEM with the addition of 10,50 and 100 nmol/L aldosterone respectively. The SP group was cultured in high glucose (4,500 mg/L) DMEM plus 10(-7)mol/L spironolactone. Immunohistochemistry, RT-PCR and Western blot were used to detect E-cadherin and alpha smooth muscle actin(alpha SMA) mRNA expression. RESULTS: RT-PCR showed that compared with the LG Group, E cadherin mRNA expression in the HG group was significantly lower, and alpha-SMA mRNA expression was significantly increased(P<0.05). E-cadherin mRNA expression in the 50 nmol/L Aldo group and 100 nmol/L Aldo group was significantly lower than that in the HG group, while the expression of alpha-SMA mRNA was significantly increased in the HG group(P<0.05), with a dose-dependent relationship with aldosterone(r=-0.70,P<0.05;r=0.67, P<0.05). E-cadherin mRNA in the SP group was significantly higher,while alpha-SMA mRNA expression was lower than that in the HG group(P<0.01). Immunohistochemistry and Western blot showed that compared with the LG group, E-cadherin protein expression was significantly reduced, and alpha-SMA expression was significantly increased in the HG group(P<0.01). In the 10 nmol/L Aldo, 50 nmol/L Aldo, and the 100 nmol/L Aldo groups, E-cadherin protein expression was significantly lower, and alpha-SMA protein expression was significantly higher than that in the HG group(P<0.05), with a dose-dependent relationship with aldosterone(r=-0.83,P<0.05;r=0.81, P<0.05). In the SP group, E-cadherin protein expression was higher, and alpha-SMA protein level was lower than that in the HG group(P<0.05). CONCLUSION: Aldosterone can promote EMT of tubular epithelial cells in a high sugar milieu, leading to renal interstitial fibrosis in Diabetic nephropathy. Spironolactone can inhibit high glucose-induced renal tubular epithelial cells EMT, which may be an important mechanism for the inhibition of renal interstitial fibrosis. PMID- 20360643 TI - [Preparation and identification of monoclonal antibody against human testis development related gene 1]. AB - OBJECTIVE: To construct a prokaryotic plasmid to express the testis development related gene 1 (TDRG1) recombinant protein and obtain anti-TDRG1 mAb by immunizing mice, and to identify the biological properties of the mAb. METHODS: The coding sequence of TDRG1 was amplified by RT-PCR from normal human testis tissue and cloned into the vector pET21, and then was expressed in the E. coli BL 21(DE3) to get TDRG1 recombinant protein. The purified TDRG1 recombinant protein was injected to immunize the BALB/C mice to develop anti-TDRG1 mAb. Splenocytes of the immunized mice were collected and fused with the mouse myeloma cell line Sp2/0 cells. The hybridoma cells that secreted anti-TDRG1 mAb were subcloned with limited dilution. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate titers and subtypes of mAb. Western blot and immunohistochemistry were used to detect specificity of mAb. RESULTS: The prokaryotic plasmid expressing the recombinant protein was constructed, and the TDRG1 recombinant protein was expressed and purified. Two hybridoma cell lines that secreted anti-TDRG1 mAb were obtained. The titer of the mAb in ascites was 1 : 1.6 x 10(6), and the subtype of the mAb was IgG(1). Westem blot and immunohistochemistry analysis indicated the mAb showed specific combination with TDRG1 protein in human testes. CONCLUSION: The TDRG1 recombinant protein is highly purified and has strong antigenicity. The anti-TDRG1 mAb is produced successfully. PMID- 20360644 TI - [Biopanning of HCV antigen epitopes from a random 12-peptide library by anti hepatitis C virus polyclonal antibody]. AB - OBJECTIVE: To analyze the epitopes of anti-hepatitis C virus(HCV)antibodies by peptide library biopanning. METHODS: Phage random peptide library of 12 amino acids was immunoscreened with purified IgG from the sera of hepatitis C patients. Positive clones which were obtained after 3 rounds of biopanning were detected by ELISA and 4 of them were sequenced. RESULTS: After 3 rounds of screening, the radio of output to input increased from (4.6 x 10(-4))% to (5.3 x 10(-2))%, meaning the enrichment was effective. At the third round of screening, all the selected clones proved to specifically react with the sera for immunoscreening. Four positive phage clones were sequenced, which shared a very conservative sequence and was named as C1. Its inserting sequence in the coat protein III was deduced to be GSMSPYVRWYTP, and the positive rate of C1 reacted with 20 cases of HCV patients was 85%. CONCLUSION: The antigen-mimic peptide C1 is successfully screened from 12 random phage peptide library and it has some diagnostic value. PMID- 20360645 TI - [Expression of HLA-G protein in placental tissues and its influence on Th1/Th2 cytokines in peripheral blood in patients with intrahepatic cholestasis of pregnancy]. AB - OBJECTIVE: To investigate the changes of human leukocyte antigen-G (HLA-G) protein expression and Th1/Th2 type cytokines in intrahepatic cholestasis of pregnancy (ICP) and their relativity to the etiology of ICP. METHODS: Peripheral blood and placental tissues were obtained from 26 ICP patients (the ICP group) and 22 normal pregnant women (the NP group) in the operation room for Cesarean birth. Immunohistochemistry was used to detect the expression of HLA-G protein in the placental tissues. Meanwhile we tested the concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) by enzyme-linked immunosorbent assay (ELISA) in the peripheral blood and checked the levels of TBA in the serum. RESULTS: TBA level in the ICP group was (27.05+/-6.08) micromol/L, significant higher than that in the NP group (4.35+/-2.68) micromol/L (P<0.01). The positive expression of HLA-G protein in extravillous trophoblast in the ICP group was significantly lower than that in the NP group (P<0.01). The mean optical density (MOD) of positive expression of HLA-G protein in the placenta tissues in the ICP group (52.91+/-7.19) was significantly lower than that in the NP group (69.26+/ 7.72) (P<0.01). The concentration of TNF-alpha was significantly higher in the ICP group (101.31+/-19.30) pg/mL than that in the NP group (54.51+/-23.72) pg/mL (P<0.01). The concentration of IL-4 was lower in the ICP group (22.16+/-6.55) pg/mL than that in the NP group (31.69+/-8.25) pg/mL (P<0.01). The ratio of TNF alpha/IL-4 was higher in the ICP group (4.52+/-1.91) than that in the NP group (1.72+/-0.61) (P<0.01). There was a negative correlation between the MOD of HLA-G protein and TNF-alpha (r=-0.98, P<0.01) in the ICP group. No correlation with IL 4 and TNF-alpha/IL-4 was seen (P>0.05). There was a positive correlation between TBA and TNF-alpha (r=0.99, P<0.01), and a negative correlation between TBA and the MOD of HLA-G protein (r=-1.00, P<0.01) in the ICP group. No correlation with IL-4 and TNF-alpha/IL-4 was seen (P>0.05). CONCLUSION: There is an imbalance of Th1/Th2 cytokines to the Th1 type in the peripheral blood of ICP patients. The expression of HLA-G protein in the placenta of ICP patients decreases, leading to an increase of Th1 type cytokines that may be one of the reasons for liver destroy in ICP. PMID- 20360646 TI - [Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers]. AB - OBJECTIVE: To determine the aberrant methylation status of RASSF1A,p16 and DAPK gene promoter region in induced sputum from lung cancer patients and the value of their combined detection in diagnosing lung cancers. METHODS: Methylation specific PCR (MSP) was used to detect the promoter methylation status of RASSF1A, p16, and DAPK genes in induced sputum and pathological tissues from 82 patients with lung cancers and 25 patients with pulmonary benign lesion. We also analyzed the relation between methylation status and clinical pathological data. RESULTS: The positive rates of promoter methylation of RASSF1A, p16, and DAPK genes in pathological tissues from patients with lung cancers were 63.4%, 59.8%, and 58.5%, respectively,and those in induced sputum were 54.9%, 48.8%, and 51.2%, respectively. The promoter methylation of RASSF1A,p16, and DAPK genes were not detected in patients with pulmonary benign lesion. There was a significant difference between the lung cancer group and pulmonary benign lesion group (P<0.05). The methylation rate of RASSF1A gene was significantly lower in the middle and high differentiation and non-metastastic lymph node of lung cancer tissues than that in the poor differentiation and the metastatic lymph node of lung cancer tissues(P<0.05), and was not correlated with age, sex, smoking index, clinical stage, and pathological types.The methylation rate of p16, and DAPK genes was not significantly correlated with all the above mentioned factors (P>0.05). The methylation rate of joint detecting RASSF1A, p16, and DAPK genes was 73.2%. CONCLUSION: Joint detection for promoter hypermethylation of RASSF1A, p16, and DAPK genes in induced sputum may be used as a simple and effective index of the diagnosis and prognose of lung cancers, and can improve the positive rate. PMID- 20360647 TI - [Effect of valsartan on ultrastructure in the brain tissue and expression of Klotho gene in spontaneously hypertensive rats]. AB - OBJECTIVE: To observe the effect of valsartan on brian ultrastructure, Klotho gene and micro-inflammatory factor [intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-l(VCAM-1)] expression in spontaneously hypertensive rat models. METHODS: Ten male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided into a hypertension group and a valsartan intervention group, while another 5 Wistar-kyoto rats were set as a normal contrast group. The brain ultrastructure of the 2 groups was observed by electron microscope. The expression of micro-inflammatory factor (ICAM-1 and VCAM 1)and Klotho gene was detected with RT-PCR, immunohistochemistry, and Western blot, respectively. RESULTS: The cerebral neuron damage of spontaneously hypertensive rats whose ultrastructure showed cell-pyknosis, chromatin margination and typical apoptotic body formation were alleviated after the intervention of valsartan. RT-PCR showed that the gene expression of Klotho increased while ICAM-1 and VCAM-1 decreased after valsartan intervention. Immunohistochemistry and Western blot also showed that the protein expression of Klotho increased, while ICAM-1 and VCAM-1 decreased after valsartan intervention. CONCLUSION: Valsartan can improve the brain ultrastructure of spontaneously hypertensive rats by increasing the expression of Klotho. PMID- 20360648 TI - [Delayed neuroprotective effect of sevoflurane on the expression of NF-kappaB following transient focal ischemia-reperfusion in rats]. AB - OBJECTIVE: To explore the delayed neuroprotective effect of sevoflurane on the expression of NF-kappaB in rat models of transient focal ischemia-reperfusion. METHODS: Adult male Sprague-Dawley rats (220 approximately 300 g) were randomly assigned into 3 groups:an ischemia-reperfusion (I/R) group, and a 2.5% Sevoflurane (Sevo1) group, and a 4.0% sevoflurane (Sevo2) group. All the rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 hours. The rats in the I/R group were exposed to pure oxygen 60 min at 24 h before MCAO. Sevoflurane preconditioning was induced 24 h before brain ischemia by exposing the rats to 2.5% or 4.0% sevoflurane + oxygen for 60 min. The effects of sevoflurane on the brain was analyzed by evaluating the infarct volume and the expression of NF-kappaB protein through 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and immunohistochemistry at 24 and 72 h after the reperfusion. RESULTS: The infarct volumes were significantly reduced in the Sevo1 and Sevo2 groups at 24 and 72 h after the reperfusion, compared with the I/R group. The expression of NF-kappaB in the ischemic territory increased after cerebral ischemia, sevoflurane could remarkably decrease the expression of NF-kappaB in 24 and 72 h after the reperfusion. CONCLUSION: Sevoflurane inhibits the expression of NF-kappaB protein during focal ischemia the reperfusion,which may be part of the mechanism of its delayed neuroprotective function. PMID- 20360649 TI - [Soft tissue repairing and functional reconstruction in limb salvage operation on extremity bone malignant tumors]. AB - OBJECTIVE: To investigate the effect and the significance of soft tissue repairing and functional reconstruction in limb salvage operation on extremity malignant bone tumors by individualized prosthesis replacement after malignant tumor resection with the help of Neo-adjuvant chemo-therapy. METHODS: A total of 78 patients with malignant bone tumor were recruited, including 42 males and 36 females. Aged 19~61, with an average of (29.12+/-9.47).Tumor in 14 patients was in the proximal humerus, 11 in the proximal femur, 27 in the distal femur, 3 in femoral middle part, and 23 in the proximal tibial. There were 29 cases of osteogenic sarcoma, 18 chondroma sarcomatosum, 7 malignant enchondroma with pathological fracture, 20 malignant giant cell tumor,and 4 malignant inflammatory myofibroblastoma of the bone. Soft tissue repairing and functional reconstruction were carried out together with individualized prosthesis replacement. The type of the prostheses was as follows: 14 patients had long stem humerus head prosthesis, 50 made hinged knee prostheses with femoral or tibial component, 3 whole femur replacements, 7 long stem femoral head prostheses, 4 long stem hip prostheses. RESULTS: All patients were followed up for an average of (26.80+/-8.06) months (4~37 months) and postoperative functions were estimated according to Enneking system. Among the 78 patients, results in 48 (61.5%) were excellent, 17 (21.8%) were good, 10 (12.8%) were fair, and 3(4.9%) were poor. The satisfactory rate was 83.3%. CONCLUSION: Soft tissue repairing and functional reconstruction in limb salvage operation on extremity bone malignant tumors by individualized prosthesis replacement not only spare the limbs, but also keep their function.It can remove the psychologic obstacles caused by extremity absence, and is effective for bone malignant tumor. PMID- 20360650 TI - [Effect of epidural drainage and dural tenting suture on epidural hematoma in 145 cases of craniotomy]. AB - OBJECTIVE: To evaluate the efficacy of dural tenting suture and epidural drainage in craniotomy. METHODS: In 145 cases of intracranial lesions, dural tenting suture and epidural drainage were performed to prevent epidural hematoma. RESULTS: Postoperative computed tomography (CT) showed no epidural hematoma required surgery in both groups. CONCLUSION: Both dural tenting suture and epidural drainage are effective in preventing epidural hematoma. Hemostasis is the key step. Dural tenting suture without epidural drainage relieves psychological stress. It decreases the risk of intracranial infection and avoids some unusual complications. PMID- 20360651 TI - The role of cell biology and leaflet remodeling in the progression of heart valve disease. AB - Heart valves are complex tri-layered structures that ensure the unidirectional flow of blood. Scientists are actively investigating how characteristics of the two major cell types, valvular endothelial cells (VECs) and valvular interstitial cells (VICs), and their mechanical relationships with the valvular extracellular matrix promote structural integrity and age-related remodeling. Abnormal changes in VECs, VICs, and the extracellular matrix at the molecular level lead to gross tissue malformations and dysfunction. This review addresses current advances in the field of valve biology, mechanisms underlying valvular leaflet remodeling, and common pathological manifestations. Improving our understanding of heart valve biology, the impact of cardiovascular drugs, and remodeling changes will be critical to the development of novel therapies for heart valve diseases. PMID- 20360652 TI - Structure, function, and dynamics of the mitral annulus: importance in mitral valve repair for myxamatous mitral valve disease. AB - The first successful open repair of a mitral valve for mitral insufficiency was performed by Dr. Dwight McGoon in 1958. He employed a triangular plication of the prolapsing portion of the posterior leaflet and no annuloplasty. Other surgeons subsequently introduced a variety of techniques. Of these, the repair techniques developed by Dr. Alain Carpentier, which incorporated both leaflet repair by a quadrangular resection and annuloplasty, soon proved to be the most effective and reproducible method at that time. Because of the limited knowledge of normal and pathological mitral valve function available in the late 1960s, this repair was based on anatomical and pathological studies obtained through autopsies as well as intraoperatively. While the Carpentier technique continues to be used widely, most centers have found it difficult to repair more than 50-60% of insufficient valves. Only a few centers have achieved higher early success rates. Most have done this by modifications of the classical techniques. Recent reports have documented high rates of recurrence of significant mitral regurgitation in the 5- to 10-year follow-up interval. Our own experience with the Carpentier technique began in 1983. By this time, a growing body of knowledge was accumulating that demonstrated the highly dynamic behavior and important interactions of the six elements of the mitral complex: the left atrium, leaflets, mitral annulus, chordae, papillary muscles, and left ventricle. Because the Carpentier technique uses leaflet resection and rigid or semi-rigid annuloplasty rings, it produces a substantial disruption of these important functions. The mitral annulus is flattened and fully immobilized, and the leaflets also are flattened at their annular attachment. The loss of surface area amd distortion of the subvalvular chordae and papillary muscles from the leaflet resection produces diminished or absent leaflet movement. The entire mitral valve is left in a highly stressed state. In order to overcome these problems, we developed a new technique called the American Correction (Figure 1). The mitral leaflets are never resected, regardless of size. Artificial polytetrafluoroethylene (PTFE) chordae are used to correct localized leaflets prolapse. A full, totally flexible annuloplasty ring is utilized. Most importantly, all adjustments of leaflet position and annular sizing are done during inflation of the heart, with pressurized normal saline delivered at 4 liters a minute into the cavity of the left ventricle. In a controllable fashion, the left ventricular intracavitary and aortic root pressure can be elevated to systolic levels. This produces a series of reproducible changes in the leaflets and annulus that can be correlated with the normally functioning mitral valve in the beating heart (Figures 2-5). PMID- 20360653 TI - Functional valve assessment: the emerging role of cardiovascular magnetic resonance. AB - The prevalence of valvular heart disease is increasing along with the life span of the population. In assessing individuals with valve disease, echocardiography is the primary imaging modality used by clinicians both for initial assessment and for longitudinal evaluation. Information regarding valve morphology and function, cardiac chamber size, wall thickness, ventricular function, and estimates of pulmonary artery pressures can be readily obtained and integrated to formulate an assessment of valve disease severity. In some instances, body habitus or the presence of coexisting lung disease may result in suboptimal acoustic windows on echocardiography, which may lead to technically difficult studies. Additionally, in some patients, information from clinical history and physical examination or other diagnostic tests may be discordant with echocardiographic findings. In these instances, there is a significant clinical role for cardiovascular magnetic resonance (CMR). The diagnostic capabilities of CMR have increased substantially over the past 20 years due to hardware and software advances. Today, CMR has a number of unique advantages over other imaging modalities - primarily, it provides a view of the entire heart without limitations from inadequate imaging windows or body habitus. Furthermore, CMR can obtain imaging data in any imaging plane prescribed by the scan operator, which makes it ideal for accurate investigation of all cardiac valves - aortic, mitral, pulmonic, and tricuspid. In addition, CMR for valve assessment is noninvasive, free of ionizing radiation, and in most instances does not require contrast administration. Since a comprehensive review of the role of CMR in all valve lesions is beyond the scope of this article, we will focus on the most common valvular indication for performance of clinical CMR techniques and an overview of selected validation and reproducibility studies. The objectives of a comprehensive CMR study for evaluating mitral insufficiency are threefold: 1) to provide insight into the mechanism of mitral insufficiency, and 3) to discern the consequences of the lesions including the effects on left ventricular (LV) volume, LV systolic function, and left atrial volumes. In most instances this information can be obtained without the need for intravenous contrast agents (gadolinium). Therefore, CMR can be performed even in patients with severe renal failure. PMID- 20360654 TI - New recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound. AB - Valve replacement remains common in the adult patient despite advances in valve repair. While a physical examination can alert the clinician to the presence of valve dysfunction, diagnostic methods are often needed to assess the function of the prosthesis. Echocardiography with Doppler is currently the method of choice for non-invasive evaluation of prosthetic valves. A recently published "Guidelines and Standards" document from the American Society of Echocardiography (ASE) offers a review of echocardiographic and Doppler techniques used in assessing prosthetic valves and, for the first time, provides general recommendations for evaluating prosthetic valve function. The guidelines have been endorsed by prominent national and international professional health organizations including the American Heart Association, the American College of Cardiology, and the European Association of Echocardiography. I was honoured to chair the ASE writing group of international experts on prosthetic valves and will review the salient features of these guidelines, particularly pertaining to the commonly implanted valves in the aortic and mitral positions. PMID- 20360655 TI - Museum of imaging. PMID- 20360656 TI - Bicuspid aortic valve and associated aortopathy: surgical considerations. AB - The human aortic valve is normally a tricuspid structure but may occur as bicuspid or quadricuspid structures (Figure 1). Biscuspid aortic valve (BAV) is one of the most common congenital heart anomalies and the most common congenital anomaly in adults, occurring in 0.5-2% of the population based on echocardiography and autopsy series. It is an inherited defect that appears to occur in an autosomal dominant pattern. BAV is the cause of aortic stenosis in 70 85% of pediatric cases and about 50% of adult cases. Indications for aortic valve replacement (AVR) in BAVs is the same as rheumatic or senile calcific degeneration aortic valves. BAVs are different, however, in that the tissue pathology is not limited to the valves' leaflets but extends from the left ventricular outflow tract to the ascending thoracic aorta. BAVs are associated with several congenital anomalies, infective endocarditis, and acute thoracic aortic emergencies such as aneurysm and dissection. These associations lead to surgical considerations different from other aortic valve pathologies. PMID- 20360657 TI - Contemporary aortic valve therapy. AB - Aortic valve disease imparts a pressure or volume overload on the left ventricle (LV). If this load is severe and prolonged, it eventually leads to LV damage, congestive heart failure (CHF), and death. These mechanical problems ultimately require mechanical correction in the form of valve replacement or repair, and the timing and types of mechanical therapy will be the main thrusts of this article. PMID- 20360658 TI - A Smeloff-Cutter mechanic aortic valve: retired after 35 years of service (1974 2009). PMID- 20360659 TI - Michael E. BeBakey, M.D.: the real man behind the genius. PMID- 20360660 TI - Liraglutide (Victoza) for type 2 diabetes. AB - Liraglutide (Victoza-Novo Nordisk), a glucagon-like peptide-1 (GLP-1) receptor agonist given by subcutaneous injection, has been approved by the FDA for treatment of patients with type 2 diabetes. It can be used alone or in addition to oral antidiabetic drugs such as metformin (Glucophage, and others) or glimepiride (Amaryl, and others). Liraglutide is not recommended for first-line therapy and is not approved for use with insulin. PMID- 20360661 TI - Plerixafor (Mozobil). PMID- 20360662 TI - Sjogren's syndrome: correlation between histopathologic result and clinical and serologic parameters. AB - AIM: Sjogren's syndrome (SS) represents a challenging illness to diagnose properly and, because of the serious complications such as lymphoma, it is important to reach a correct diagnosis in early stages. Aim of this retrospective study was to evaluate the correlation between histopathologic result of minor salivary gland biopsy and clinical and serologic parameters for the diagnosis of SS. METHODS: We evaluated 360 biopsies, taken from the lower lip, of 360 patients (18 males) on suspicion that they were suffering from SS. The Chisolm and Mason classification was used to state the diagnosis of SS. For each patient, the medical history and the symptoms were evaluated, and diagnostic tests were performed. The revised rules of the American-European Consensus Group Criteria were used to diagnose primary and secondary SS. For the statistical analysis we used the Chi(2) test; a difference of P<0.05 was considered significant. RESULTS: Considering the statistical correlation between a focal score > or =1 and the serological data, it was noted that a positive score was significantly correlated to all serological parameters examined (P<0.0001). A significant correlation was also found between a positive biopsy score and Schirmer's test and Rose Bengal test (P<0.0001). However, with regard to the clinical data, a significant correlation was found only for two parameters: xerostomia (P<0.0001) and parotid swelling (P<0.05). CONCLUSION: Minor salivary gland biopsies are of great diagnostic value in detecting SS. However, for the diagnosis of SS both clinical and serologic parameters should be considered. The data obtained from the present survey reveal that the serologic markers are more predictive than clinical parameters for a positive biopsy score. PMID- 20360663 TI - Fixation of mandibular fractures with plates or miniplates: prospective study. AB - AIM: The choice of a more adequate internal fixation system in the treatment of mandibular fractures still originates controversy in the literature. The purpose of this study was to evaluate the effectiveness of internal fixation systems in the fixation of mandibular fractures, comparing indications and postoperative results between 2.4-mm plates and 2.0-mm miniplates. METHODS: A total of 42 consecutive patients with 71 mandibular fractures that had undergone either 2.4 mm plates (N.=20) or 2.0-mm miniplates (N.=22) were prospectively analyzed. Patients had a minimum follow-up of 6 months. Statistical analyses were made in the comparison between systems. RESULTS: There was no significant difference in the choice of systems as to age and characteristics of the fractures, but in patients with systemic diseases or chronic substance abuse, as well as in exposed fractures, with more frequency of 2.4-mm plates. 2.0-mm miniplates presented better recovery of jaw opening in the postoperative period. Temporary facial nerve deficit was observed exclusively in the case of extraoral approach. Both systems presented low rate of complications which required reoperation, however 2.0-mm miniplates presented better efficacy when compared to 2.4-mm plates. CONCLUSION: In conclusion, 2.0-mm miniplates should be always used when possible in the fixation of mandibular fractures, respecting their contraindications. PMID- 20360664 TI - Two typologies of endodontic instrument handle are here investigated for tactility modifications. AB - AIM: The purpose of this comparative study was to evaluate possible modifications of tactility (deep and discriminative tactile sensitivity) using manual endodontic instruments equipped with traditional handles compared with innovative silicone handle versions. METHODS: Sixteen subjects were selected and supplied with resin Endo-Training-Block simulators, latex gloves and manual endodontic instruments with diameters ranging from 10 to 40 mm. All instruments had traditional and silicon handles. The investigation of deep and discriminative tactile sensitivity was performed at 0, 15, 30, and 45 minutes of the manual instrumentation with an esthesiometer. We obtain each of our data from the median of three consecutive measurements. The results were then statistically analyzed thanks to the ANOVA test: P=0.003 for subjects, P<0.001 for time factor, and P=0.010 for sensitivity-time interaction. RESULTS: We observed a better tactility with silicone handle instruments, comparing the two kinds of handle (regardless of the finger tested) as well as singly analyzing the thumb and index finger. CONCLUSION: Despite the sample limited extension, the loss of deep cutaneous and discrimination sensitivity seems to be reduced using silicone handles, most likely favoring an improvement of the working performance. PMID- 20360665 TI - Dietary habits of a school population and implications for oral health. AB - AIM: The study analyzes the consumption of cariogenic foods in a population of children between 6 and 10 years old. METHODS: Transversal descriptive study on a sample of 369 children who first attended to the Department 9 Dentistry dental office of the Valencia Region Health Agency (Spain). A self-administered food consumption frequency questionnaire was used to evaluate how often the food on the list were consumed by the children. RESULTS: Sticky sugar-rich foods, sugared milk and dairy products, food containing starch and sugar, sugary liquids and food with semihydrolyzed starch were consumed by over 50% of the sample at main meals and between meals. The mean intake of all these food groups, was over five times a week. The older children ate more fruit and foods rich in semihydrolyzed starch at main meals. Sweetened medication significantly reduced with age. Sugar free sweets were consumed by almost 60% of the sample. CONCLUSION: The study shows a high intake of food with cariogenic potential, in particular processed food with added sugar and food with semihydrolyzed starch consumed between meals. This situation indicates the need to include health education programs in our population focused to improve the dietary habits of children and teenagers. PMID- 20360666 TI - Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review. AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an area of uncovered bone in the maxillo-facial region that did not heal within 8 weeks after identification by health care provider, in a patient who was receiving or had been exposed to Bisphosphonate Therapy (BPT) without previous radiation therapy to the craniofacial region. Low-grade risk of ONJ is connected with oral BPT used in the treatment of osteopenia, osteoporosis and Paget's disease (from 0.01% to 0.04%) while higher-grade risk is associated with intravenous (IV) administration in the treatment of multiple myeloma and bone metastases (from 0.8% to 12%). The management of BRONJ currently is a dilemma. No effective treatment has yet been developed and interrupting BPT does not seem to be beneficial. Temporary suspension of BPs offers no short-term benefit, whilst long term discontinuation (if systemic conditions permit it) may be beneficial in stabilizing sites of ONJ and reducing clinical symptoms. The use of oral antimicrobial rinses in combination with oral systemic antibiotic therapy -penicillin, metronidazole, quinolones, clindamycin, doxycycline, erythromycin- is indicated for Stages I and II of Ruggiero's Staging. The role of hyperbaric oxygen therapy is still unclear but some benefits of this treatment have recently been described in association with discontinuation of BPT and conventional therapy (medical or/and surgical). Surgical treatment, in accordance to the AAOMS Position Paper, is reserved to patients affected by Stage III of BRONJ even if in the last version (2009) a superficial debridement is indicated to relieve soft tissue irritation also in the stage II (lesions being unresponsive to antibiotic treatment). Aggressive surgical treatment may occasionally results in even larger areas of exposed and painful infected bone. Surgical debridement or resection in combination with antibiotic therapy may offer long-term palliation with resolution of acute infection and pain. Mobile segments of bony sequestrum should be removed without exposing unaffected bone. If pathological fractures or complete mandibular involvement are observed, if the medical condition of the patients allows it the affected bone portion may be resected and primary bone reconstruction or revascularization graft may be carried out. Ozone therapy in the management of bone necrosis or in extractive sites during and after oral surgery in patients treated with BPs may stimulate cell proliferation and soft tissue healing. Laser applications at low intensity (Low Level Laser Therapy - LLLT) have been reported in the literature for the treatment of BRONJ. Biostimulant effects of laser improve reparative process, increase inorganic matrix of bone and osteoblast mitotic index and stimulate lymphatic and blood capillaries growth. Laser can be used for conservative surgery, whereby necrotic bone is vaporized, until healthy bone is reached. The Er:YAG laser wavelength has a high degree of affinity for water and hydroxyapatite, hence both soft and bone tissues can be easily treated. An additional advantage of the Er:YAG laser is its bactericidal and possible biostimulatory action, accelerating the healing of both soft and bone tissues, in comparison to conventional treatments. Long-term, prospective studies are required to establish the efficacy of drug holidays in reducing the risk of BRONJ for patients receiving oral BPs even if it has been suggested that BPT may be discontinued for three months before the surgical procedures and bone turnover markers (CTx, NTx, PTH, 1,25-dihydroxy vitamin D) may be checked. However it must be recognized that interindividual variability, gender, age, physical activity, and seasonal and circadian variation exist that can result in difficulty in interpreting these assays and more research is needed. Laser application (LLLT and laser surgery) nowadays appears to be a promising modality of BRONJ treatment, being safe and well tolerated, and it permits the minimally invasive treatment of early stages of the disease. PMID- 20360667 TI - The importance of immediately loaded immediate post-extractive implants in esthetical rehabilitation: case series. AB - The aim of this paper was to estimate, in a retrospective way, integration of hard and soft tissues in immediately loaded immediate postextractive implants. Benefits of this technique could be: single stage surgery, biological saving of tissues, aesthetic management of edentulism, good integration of both hard and soft tissues. Immediate loading of a postextractive implant seems also to produce a positive effect on the quality of perimplant soft tissues. The implants used in the present study have some advantages such as high auto-threading and auto tapping ability, progressive increase of the thickness of the threads, at the apical and coronal level. All these features have helped to obtain a high primary stability. PMID- 20360668 TI - Vascularized fibula free flap for implant rehabilitation in the case of extreme atrophy. AB - The skeletal reconstruction in cases of extreme atrophy like a class VI Cawood classification can be carried out using free bone flaps. They represent a valid option for preprosthetic rehabilitation of atrophic maxillas. Over the last 5 years, the use of vascularized bone transplants, aimed at implant-prosthetic rehabilitation, has become a practice, which has gradually found the right indications and the range of applications, which are now widely acknowledged. The key to success in the use of free flaps lies in the identification of the correct indications for use, in meticulous programming and the particular motivation that this type of patient has for reacquiring optimum masticatory functions. The final prosthetic implant rehabilitation must be prosthetically guided and an accurate preoperative planning is of fundamental importance for restoring masticatory functions and esthetic harmony to the patient through a fixed prosthesis. The authors present a case of a rehabilitation of an extreme maxillary and mandibular atrophy. PMID- 20360669 TI - Interim results: influenza A (H1N1) 2009 monovalent and seasonal influenza vaccination coverage among health-care personnel - United States, August 2009 January 2010. AB - Since 1986, the Healthcare Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP) have recommended that all health-care personnel (HCP) be vaccinated annually for influenza. Since 1989, overall influenza vaccination coverage among HCP has never exceeded 49% in any season, according to estimates from the National Health Interview Survey. In August 2009, ACIP recommended that HCP be one of five initial target groups to receive the influenza A (H1N1) 2009 monovalent vaccine when it first became available. This report summarizes results of a population based panel survey administered via the Internet during January 2010 to a nationally representative sample of 1,417 HCP to assess vaccination coverage. By mid-January 2010, estimated vaccination coverage among HCP was 37.1% for 2009 pandemic influenza A (H1N1) and 61.9% for seasonal influenza. Overall, 64.3% received either of these influenza vaccines, higher coverage than any previous season, but only 34.7% of HCP reported receiving both vaccines. The existence of an employer requirement for vaccination at the facility where the respondent was employed was associated with an eightfold greater likelihood of 2009 H1N1 vaccination compared with respondents employed by facilities with neither requirement nor recommendations; likewise, the existence of a recommendation for vaccination was associated with a fourfold greater probability of 2009 H1N1 vaccination. Health-care administrators should consider influenza vaccination coverage among employees an important measure of patient safety and make appropriate efforts to increase coverage in future seasons. PMID- 20360670 TI - Interim results: state-specific influenza A (H1N1) 2009 monovalent vaccination coverage - United States, October 2009-January 2010. AB - In July 2009, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for the use of influenza A (H1N1) 2009 monovalent vaccine. Distribution of 2009 H1N1 vaccine in the United States began on October 5, using a system that allocated available vaccine to states proportional to their populations. By the end of 2009, approximately 61 million persons had been vaccinated. By January 29, 2010, approximately 124 million doses had been distributed. To provide preliminary state-specific estimates of 2009 H1N1 vaccination coverage as of the end of January, CDC analyzed results from the Behavioral Risk Factor Surveillance System (BRFSS) and the National 2009 H1N1 Flu Survey (NHFS), using data collected during November 2009--February 2010. This report summarizes the results of that analysis, which found that, by state, estimated 2009 H1N1 vaccination coverage as of the end of January among persons aged >/=6 months ranged from 12.9% to 38.8% (median: 23.9%). Median coverage was 36.8% for children aged 6 months--17 years, 20.1% for adults aged >/=18 years, and 33.2% for persons in the ACIP initial target group. The wide variation in 2009 H1N1 vaccination rates among states suggests opportunities for improvement in future seasons, such as maintaining and increasing the reach of networks of private providers as vaccinators and distributing more vaccine through public venues (e.g., schools). PMID- 20360671 TI - Surveillance for human West Nile virus disease - United States, 1999-2008. AB - PROBLEM/CONDITION: West Nile virus (WNV) is an arthropod-borne virus (arbovirus) in the family Flaviviridae and is the leading cause of arboviral disease in the United States. An estimated 80% of WNV infections are asymptomatic. Most symptomatic persons develop an acute systemic febrile illness that often includes headache, myalgia, arthralgia, rash, or gastrointestinal symptoms. Less than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. REPORTING PERIOD: 1999 2008. DESCRIPTION OF SYSTEM: WNV disease is a nationally notifiable disease with standardized case definitions. State and metropolitan heath departments report cases to CDC through ArboNET, an electronic passive surveillance system. Variables collected include patient age, sex, race, county and state of residence, date of illness onset, clinical syndrome, and outcome of illness. RESULTS: During 1999-2008, a total of 28,961 confirmed and probable cases of WNV disease, including 11,822 (41%) WNV neuroinvasive disease cases, were reported to CDC from 47 states and the District of Columbia. No cases were reported from Alaska, Hawaii, Maine, or any U.S. territories. A total of 93% of all WNV patients had illness onset during July-September. The national incidence of WNV neuroinvasive disease peaked in 2002 (1.02 cases per 100,000 population) and was stable during 2004-2007 (mean annual incidence: 0.44; range: 0.39-0.50). In 2008, the incidence was 0.23 per 100,000 population, compared with 0.41 in 2007 and 0.50 in 2006. During 1999-2008, the highest incidence of neuroinvasive disease occurred in West North Central and Mountain states. Neuroinvasive disease incidence increased with increasing age, with the highest incidence (1.35 cases per 100,000 population) occurring among persons aged >or=70 years. The hospitalization rate and case-fatality ratio increased with increasing age among persons with neuroinvasive disease. INTERPRETATION: The stability in reported incidence of neuroinvasive disease during 2004-2007 might represent an endemic level of WNV transmission. Whether the incidence reported in 2008 represents a decrease that will continue is unknown; variations in vectors, avian amplifying hosts, human activity, and environmental factors make predicting future WNV transmission levels difficult. PUBLIC HEALTH ACTION: Surveillance of WNV disease is important for detecting and monitoring seasonal epidemics and targeting prevention and control activities. Public health education programs should focus on older persons, who are at increased risk for neurologic disease and poor clinical outcomes. In the absence of an effective human vaccine, WNV disease prevention depends on community-level mosquito control and household and personal protection measures. PMID- 20360672 TI - A novel approach for documenting phosphenes induced by transcranial magnetic stimulation. AB - Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)(1) of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold) is a well established measure of visual cortical excitability and is used to study cortico-cortical interactions, functional organization (2), susceptibility to pathology (3,4) and visual processing (5-7). Phosphenes are typically defined by three characteristics: they are observed in the visual hemifield contralateral to stimulation; they are induced when the subject s eyes are open or closed, and their spatial location changes with the direction of gaze (2). Various methods have been used to document phosphenes, but a standardized methodology is lacking. We demonstrate a reliable procedure to obtain phosphene threshold values and introduce a novel system for the documentation and analysis of phosphenes. We developed the Laser Tracking and Painting system (LTaP), a low cost, easily built and operated system that records the location and size of perceived phosphenes in real-time. The LTaP system provides a stable and customizable environment for quantification and analysis of phosphenes. PMID- 20360673 TI - [Prognosis of long tubular bone strength changes in surgery of chronic osteomyelitis]. AB - Mineral bone density (MBD) in osteomyelitic focus and symmetric intact tubular bone was compared in 54 patients. Changes of MBD values were also measured after surgical treatment (bone trepanation or osteonecroectomy with bone plasty). Thus, MBD, and, therefore, bone strength, was mostly higher in pathologic focus then in the healthy bone. Operative treatment showed no negative influence on MBD. PMID- 20360674 TI - [Hermetization of aortic sutures - the comparative analysis of methods]. AB - Leakage of the ascending aortic sutures after the aortic valve replacement with the use of various methods of surgical hemostasis was studied. Results of 244 operations were analyzed. Thus, aortic leakage took place in 50 (20,5%) patients. One- or two-fold sewing was successfully used in 16 (32%) cases. The rest benefited from aortic suture fixation with the use of pericardial flap. Algorythm, implying usage of the auto- or xenopericardial flap after two-fold sewing failure, enabled exclusion of repeated aorta cross-clamping, decrease of the blood loss and hemotransfusion, and, therefore, decrease of postoperative complication and lethality rates. PMID- 20360675 TI - [The use of self-expanding metal stents in tumors of biliopancreatoduodenal zone]. AB - Nitinol self-expanding stents were used in treatment of 15 patients with blastomatous lesions of biliopancreatoduodenal zone. Stenting was successful in all cases, long-term results were obtained in all patients. Death occurred in 8 patients within 5,5-11 month after stent insertion. 7 patients remain under observation. In 6 patients nitinol stents remain open with no signs of occlusion from 2,5 to 15 months' observation period. Jaundice recurred in one patient after 11 month after the insertion due to stent occlusion. Thus, stenting proved to be an effective and safe method of bile flow restoration by tumor biliary tract obstruction. PMID- 20360676 TI - [Complications after radio-frequency thermoablation of liver tumors]. AB - Results of treatment of 124 patients (228 operations) were analyzed. Complication rate was 19.2%, whereas severe complications were observed in 4.3%. Complications, requiring minimally invasive surgery, on the contrary, conservative treatment , as well as risk actors were defined. Possibilities of radio-frequency thermoablation complications prophylaxis were suggested. PMID- 20360677 TI - [The choice of surgical tactics in patients with unstable hemostasis and gastroduodenal ulcer bleeding]. AB - Treatment results of 476 patients with acute gastroduodenal ulcer bleeding were analyzed. Men comprised 75% (n=357), women - 25% (n=119). All patients were divided in two groups. Treatment principles of patients of the first group (36.8%; n=175) were based on active conservative treatment. Surgery was performed in 70.3%, postoperative lethality comprised 12.2%, overall mortality was 9.7%. Second group consisted of 301 patients (63.2%). Individual based active surgical treatment was performed, including clinical and endoscopic evaluation of local hemostasis, prognostic criteria of bleeding recurrence, differential approach in time, extent and method of the applied surgery. Operative treatment was used in 81.1% of patients of the second group, postoperative lethality comprised 9.8%, overall mortality was 8.0%. Emergency operations were performed in 43.6% (n=160) of all patients, early elective surgery in 56.4% (n=207). Postoperative lethality comprised 10.6%, overall mortality rate was 8.6%. Therefore, individual based active surgical treatment proved to be preferable. Gastric resection showed to be more advisable then organ-preserving operations, considering emergency ulcer surgery. PMID- 20360678 TI - [The use of intraoperative sonography in surgical treatment of brain tumors]. AB - 62 patients were operated on brain tumor using intraoperative ultrasound navigation. Method proved to be effective for tumor localization, its volume measurement, identification of the surrounding anatomic structures and choice of the optimal encephalotomy access. Intraoperative sonography enables biopsy of deep lying tumors and evaluation of radicality of the operation. Method showed to be especially effective by surgical treatment of infiltrative tumors. PMID- 20360679 TI - [Surgical treatment of rectovaginal fistulae]. AB - The use of invertation as a surgical treatment of rectovaginal fistulae in 18 adult patients was presented. Operation technique and features of postoperative management were described. Fistula recurrence was observed in one case. Operation was suggested to be a method of choice in surgical treatment of rectovaginal fistulae of large and medium size localized in middle and lower third of vagina. PMID- 20360680 TI - Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. AB - Membrane and secretory trafficking are essential for proper neuronal development. However, the molecular mechanisms that organize secretory trafficking are poorly understood. Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. BICDR-1 expression is high during early neuronal development and strongly declines during neurite outgrowth. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. PMID- 20360681 TI - A systematic survey of in vivo obligate chaperonin-dependent substrates. AB - Chaperonins are absolutely required for the folding of a subset of proteins in the cell. An earlier proteome-wide analysis of Escherichia coli chaperonin GroEL/GroES (GroE) interactors predicted obligate chaperonin substrates, which were termed Class III substrates. However, the requirement of chaperonins for in vivo folding has not been fully examined. Here, we comprehensively assessed the chaperonin requirement using a conditional GroE expression strain, and concluded that only approximately 60% of Class III substrates are bona fide obligate GroE substrates in vivo. The in vivo obligate substrates, combined with the newly identified obligate substrates, were termed Class IV substrates. Class IV substrates are restricted to proteins with molecular weights that could be encapsulated in the chaperonin cavity, are enriched in alanine/glycine residues, and have a strong structural preference for aggregation-prone folds. Notably, approximately 70% of the Class IV substrates appear to be metabolic enzymes, supporting a hypothetical role of GroE in enzyme evolution. PMID- 20360682 TI - High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome. AB - Chromatin acts as a key regulator of DNA-related processes such as DNA damage repair. Although ChIP-chip is a powerful technique to provide high-resolution maps of protein-genome interactions, its use to study DNA double strand break (DSB) repair has been hindered by the limitations of the available damage induction methods. We have developed a human cell line that permits induction of multiple DSBs randomly distributed and unambiguously positioned within the genome. Using this system, we have generated the first genome-wide mapping of gammaH2AX around DSBs. We found that all DSBs trigger large gammaH2AX domains, which spread out from the DSB in a bidirectional, discontinuous and not necessarily symmetrical manner. The distribution of gammaH2AX within domains is influenced by gene transcription, as parallel mappings of RNA Polymerase II and strand-specific expression showed that gammaH2AX does not propagate on active genes. In addition, we showed that transcription is accurately maintained within gammaH2AX domains, indicating that mechanisms may exist to protect gene transcription from gammaH2AX spreading and from the chromatin rearrangements induced by DSBs. PMID- 20360683 TI - Splicing-dependent NMD does not require the EJC in Schizosaccharomyces pombe. AB - Nonsense-mediated mRNA decay (NMD) is a translation-linked process that destroys mRNAs with premature translation termination codons (PTCs). In mammalian cells, NMD is also linked to pre-mRNA splicing, usually PTCs trigger strong NMD only when positioned upstream of at least one intron. The exon junction complex (EJC) is believed to mediate the link between splicing and NMD in these systems. Here, we report that in Schizosaccharomyces pombe splicing also enhances NMD, but against the EJC model prediction, an intron stimulated NMD regardless of whether it is positioned upstream or downstream of the PTC and EJC components are not required. Still the effect of splicing seems to be direct-we have found that the important NMD determinant is the proximity of an intron to the PTC, not just the occurrence of splicing. On the basis of these results, we propose a new model to explain how splicing could affect NMD. PMID- 20360684 TI - Viral apoptosis is induced by IRF-3-mediated activation of Bax. AB - Upon infection with many RNA viruses, the cytoplasmic retinoic acid inducible gene-I (RIG-I) pathway activates the latent transcription factor IRF-3, causing its nuclear translocation and the induction of many antiviral genes, including those encoding interferons. Here, we report a novel and distinct activity of IRF 3, in virus-infected cells, that induces apoptosis. Using genetically defective mouse and human cell lines, we demonstrated that, although both pathways required the presence of RIG-I, IPS1, TRAF3 and TBK1, only the apoptotic pathway required the presence of TRAF2 and TRAF6 in addition. More importantly, transcriptionally inactive IRF-3 mutants, such as the one missing its DNA-binding domain, could efficiently mediate apoptosis. Apoptosis was triggered by the direct interaction of IRF-3, through a newly identified BH3 domain, with the pro-apoptotic protein Bax, their co-translocation to the mitochondria and the resulting activation of the mitochondrial apoptotic pathway. Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell. PMID- 20360686 TI - FTO effect on energy demand versus food intake. AB - An intronic single nucleotide polymorphism (SNP) (rs9939609) close to the fat mass and obesity associated gene (FTO) was the first SNP to be discovered with common variants linked to body mass index; at least seven studies in humans have implicated this SNP with variations in food intake and satiety, and four studies have rejected an effect on energy expenditure normalized for body weight. Fischer et al. recently constructed a mouse in which the homologous Fto gene was inactivated (Fto(-/-)) and showed that these mice were protected from obesity. This observation strongly implicates the effects of the intronic SNP rs9939609 as arising due to an effect on the closest gene (FTO). However, the suggested mechanism underlying this effect in mice was opposite to that in humans. The Fto( /-) mice showed no significant differences in food intake relative to wild-types litter-mates but had an elevated metabolic rate. The apparent contrasting effects of the gene in humans and mice is worthy of closer investigation. PMID- 20360688 TI - The human genome at ten. PMID- 20360685 TI - AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX. AB - Programmed necrosis induced by DNA alkylating agents, such as MNNG, is a caspase independent mode of cell death mediated by apoptosis-inducing factor (AIF). After poly(ADP-ribose) polymerase 1, calpain, and Bax activation, AIF moves from the mitochondria to the nucleus where it induces chromatinolysis and cell death. The mechanisms underlying the nuclear action of AIF are, however, largely unknown. We show here that, through its C-terminal proline-rich binding domain (PBD, residues 543-559), AIF associates in the nucleus with histone H2AX. This interaction regulates chromatinolysis and programmed necrosis by generating an active DNA degrading complex with cyclophilin A (CypA). Deletion or directed mutagenesis in the AIF C-terminal PBD abolishes AIF/H2AX interaction and AIF-mediated chromatinolysis. H2AX genetic ablation or CypA downregulation confers resistance to programmed necrosis. AIF fails to induce chromatinolysis in H2AX or CypA deficient nuclei. We also establish that H2AX is phosphorylated at Ser139 after MNNG treatment and that this phosphorylation is critical for caspase-independent programmed necrosis. Overall, our data shed new light in the mechanisms regulating programmed necrosis, elucidate a key nuclear partner of AIF, and uncover an AIF apoptogenic motif. PMID- 20360689 TI - A new row to hoe. PMID- 20360696 TI - Journal club. A human geneticist explores genetic diversity in Asia. PMID- 20360702 TI - River reveals chilling tracks of ancient flood. PMID- 20360701 TI - Geoengineers get the fear. PMID- 20360703 TI - Space probe set to size up polar ice. PMID- 20360704 TI - Synching Europe's big science facilities. PMID- 20360705 TI - Japan plans nuclear power expansion. PMID- 20360706 TI - Rule poses threat to museum bones. PMID- 20360708 TI - Gene flaw found in induced stem cells. PMID- 20360709 TI - Human genome at ten: Life is complicated. PMID- 20360710 TI - Human genome at ten: The human race. PMID- 20360711 TI - Human genome at ten: The sequence explosion. PMID- 20360712 TI - World view: Missing weapons. PMID- 20360713 TI - Fishermen contribute to protection of marine reserves. PMID- 20360714 TI - Sceptics and deniers of climate change not to be confused. PMID- 20360715 TI - Public database for HIV drug resistance in southern Africa. PMID- 20360716 TI - Has the revolution arrived? PMID- 20360717 TI - Multiple personal genomes await. PMID- 20360718 TI - Point: Hypotheses first. PMID- 20360719 TI - Counterpoint: Data first. PMID- 20360724 TI - Cell biology forum: Genome-wide view of mitosis. PMID- 20360725 TI - Quantum mechanics: The surf is up. PMID- 20360726 TI - Stem cells: Skin regeneration and repair. PMID- 20360727 TI - Early earth: faint young sun redux. PMID- 20360728 TI - Drug discovery: Fat-free proteins kill parasites. PMID- 20360729 TI - Physiology: There is no single p. PMID- 20360731 TI - Exotic matter: Another dimension for anyons. PMID- 20360732 TI - Astrophysics: Cosmic acceleration confirmed. PMID- 20360733 TI - Obituary: Joanne Simpson (1923-2010). PMID- 20360735 TI - Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. AB - Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the approximately 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community. PMID- 20360737 TI - Generation of electron beams carrying orbital angular momentum. AB - All forms of waves can contain phase singularities. In the case of optical waves, a light beam with a phase singularity carries orbital angular momentum, and such beams have found a range of applications in optical manipulation, quantum information and astronomy. Here we report the generation of an electron beam with a phase singularity propagating in free space, which we achieve by passing a plane electron wave through a spiral phase plate constructed naturally from a stack of graphite thin films. The interference pattern between the final beam and a plane electron wave in a transmission electron microscope shows the 'Y'-like defect pattern characteristic of a beam carrying a phase singularity with a topological charge equal to one. This fundamentally new electron degree of freedom could find application in a number of research areas, as is the case for polarized electron beams. PMID- 20360734 TI - Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. AB - Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. PMID- 20360736 TI - N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. AB - African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis. PMID- 20360738 TI - Identification of Younger Dryas outburst flood path from Lake Agassiz to the Arctic Ocean. AB - The melting Laurentide Ice Sheet discharged thousands of cubic kilometres of fresh water each year into surrounding oceans, at times suppressing the Atlantic meridional overturning circulation and triggering abrupt climate change. Understanding the physical mechanisms leading to events such as the Younger Dryas cold interval requires identification of the paths and timing of the freshwater discharges. Although Broecker et al. hypothesized in 1989 that an outburst from glacial Lake Agassiz triggered the Younger Dryas, specific evidence has so far proved elusive, leading Broecker to conclude in 2006 that "our inability to identify the path taken by the flood is disconcerting". Here we identify the missing flood path-evident from gravels and a regional erosion surface-running through the Mackenzie River system in the Canadian Arctic Coastal Plain. Our modelling of the isostatically adjusted surface in the upstream Fort McMurray region, and a slight revision of the ice margin at this time, allows Lake Agassiz to spill into the Mackenzie drainage basin. From optically stimulated luminescence dating we have determined the approximate age of this Mackenzie River flood into the Arctic Ocean to be shortly after 13,000 years ago, near the start of the Younger Dryas. We attribute to this flood a boulder terrace near Fort McMurray with calibrated radiocarbon dates of over 11,500 years ago. A large flood into the Arctic Ocean at the start of the Younger Dryas leads us to reject the widespread view that Agassiz overflow at this time was solely eastward into the North Atlantic Ocean. PMID- 20360739 TI - No climate paradox under the faint early Sun. AB - Environmental niches in which life first emerged and later evolved on the Earth have undergone dramatic changes in response to evolving tectonic/geochemical cycles and to biologic interventions, as well as increases in the Sun's luminosity of about 25 to 30 per cent over the Earth's history. It has been inferred that the greenhouse effect of atmospheric CO(2) and/or CH(4) compensated for the lower solar luminosity and dictated an Archaean climate in which liquid water was stable in the hydrosphere. Here we demonstrate, however, that the mineralogy of Archaean sediments, particularly the ubiquitous presence of mixed valence Fe(II-III) oxides (magnetite) in banded iron formations is inconsistent with such high concentrations of greenhouse gases and the metabolic constraints of extant methanogens. Prompted by this, and the absence of geologic evidence for very high greenhouse-gas concentrations, we hypothesize that a lower albedo on the Earth, owing to considerably less continental area and to the lack of biologically induced cloud condensation nuclei, made an important contribution to moderating surface temperature in the Archaean eon. Our model calculations suggest that the lower albedo of the early Earth provided environmental conditions above the freezing point of water, thus alleviating the need for extreme greenhouse-gas concentrations to satisfy the faint early Sun paradox. PMID- 20360740 TI - Curvature in metabolic scaling. AB - For more than three-quarters of a century it has been assumed that basal metabolic rate increases as body mass raised to some power p. However, there is no broad consensus regarding the value of p: whereas many studies have asserted that p is 3/4 (refs 1-4; 'Kleiber's law'), some have argued that it is 2/3 (refs 5-7), and others have found that it varies depending on factors like environment and taxonomy. Here we show that the relationship between mass and metabolic rate has convex curvature on a logarithmic scale, and is therefore not a pure power law, even after accounting for body temperature. This finding has several consequences. First, it provides an explanation for the puzzling variability in estimates of p, settling a long-standing debate. Second, it constitutes a stringent test for theories of metabolic scaling. A widely debated model based on vascular system architecture fails this test, and we suggest modifications that could bring it into compliance with the observed curvature. Third, it raises the intriguing question of whether the scaling relation limits body size. PMID- 20360741 TI - The genome of a songbird. AB - The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. PMID- 20360742 TI - Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. AB - Abnormalities in functional connectivity between brain areas have been postulated as an important pathophysiological mechanism underlying schizophrenia. In particular, macroscopic measurements of brain activity in patients suggest that functional connectivity between the frontal and temporal lobes may be altered. However, it remains unclear whether such dysconnectivity relates to the aetiology of the illness, and how it is manifested in the activity of neural circuits. Because schizophrenia has a strong genetic component, animal models of genetic risk factors are likely to aid our understanding of the pathogenesis and pathophysiology of the disease. Here we study Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22 (22q11.2) that constitutes one of the largest known genetic risk factors for schizophrenia. To examine functional connectivity in these mice, we measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wild-type mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats. Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. These data suggest how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level. Our findings further suggest that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia. PMID- 20360745 TI - A maturing European Research Council. PMID- 20360743 TI - NINJA connects the co-repressor TOPLESS to jasmonate signalling. AB - Jasmonoyl-isoleucine (JA-Ile) is a plant hormone that regulates a broad array of plant defence and developmental processes. JA-Ile-responsive gene expression is regulated by the transcriptional activator MYC2 that interacts physically with the jasmonate ZIM-domain (JAZ) repressor proteins. On perception of JA-Ile, JAZ proteins are degraded and JA-Ile-dependent gene expression is activated. The molecular mechanisms by which JAZ proteins repress gene expression remain unknown. Here we show that the Arabidopsis JAZ proteins recruit the Groucho/Tup1 type co-repressor TOPLESS (TPL) and TPL-related proteins (TPRs) through a previously uncharacterized adaptor protein, designated Novel Interactor of JAZ (NINJA). NINJA acts as a transcriptional repressor whose activity is mediated by a functional TPL-binding EAR repression motif. Accordingly, both NINJA and TPL proteins function as negative regulators of jasmonate responses. Our results point to TPL proteins as general co-repressors that affect multiple signalling pathways through the interaction with specific adaptor proteins. This new insight reveals how stress-related and growth-related signalling cascades use common molecular mechanisms to regulate gene expression in plants. PMID- 20360746 TI - Abscission accomplished by PtdIns(3)P. AB - Cytokinesis - the final step of mitosis in which the two daughter cells separate requires accumulation of specific proteins and lipids at the connecting bridge to ensure cleavage by abscission. Phosphatidylinositol-3-phosphate (PtdIns(3)P), an endosomal phosphoinositide, and FYVE-CENT, a PtdIns3P-binding protein, are found in the bridge, where they contribute to the mechanism of abscission. PMID- 20360747 TI - Cilia self-organize in response to planar cell polarity and flow. AB - Cilia drive fluid flow in development and physiology, but this requires that all cilia in a tissue orient the same way. Earlier studies indicated that both planar cell polarity (PCP) signalling and cilia-generated fluid flows could influence ciliary orientation. We now learn how asymmetric localization of PCP proteins influences the position and orientation of cilia to control the direction of flow. PMID- 20360750 TI - History of antihypertensive therapy influences the relationships of alcohol with blood pressure and pulse pressure in older men. AB - BACKGROUND: Blood pressure is known to be higher in heavy drinkers than in nondrinkers. The aim of this study was to determine whether the alcohol-blood pressure relationship is modified by therapy for hypertension in the elderly. METHODS: Men aged > or = 65 years (n = 1,396) with or without current history of antihypertensive therapy were divided into four groups by alcohol intake (non-, light (<22 g ethanol/day), heavy (> or = 22 and <44 g ethanol/day), and very heavy (> or = 44 g ethanol/day) drinkers). Blood pressure and pulse pressure were compared among the groups. RESULTS: Systolic blood pressure and pulse pressure were significantly higher in subjects receiving antihypertensive therapy than in subjects not receiving antihypertensive therapy, whereas diastolic blood pressure was not different between the two groups. In multivariate analysis with adjustment for age, smoking history, and body mass index (BMI), systolic and diastolic blood pressure and pulse pressure in the group not receiving antihypertensive therapy were significantly higher in heavy and very heavy drinkers than in nondrinkers, whereas in the group receiving antihypertensive therapy, systolic and diastolic blood pressure and pulse pressure were not different between each drinker group and the nondrinker group. CONCLUSIONS: Alcohol intake was associated with blood pressure and pulse pressure in older men not receiving therapy for hypertension but not in those receiving antihypertensive therapy. The indicated possibility that changes in drinking do not have a substantial impact on blood pressure among treated hypertensives should be examined in longitudinal studies and preferably in clinical trials. PMID- 20360751 TI - Perinatal micronutrient supplements ameliorate hypertension and proteinuria in adult fawn-hooded hypertensive rats. AB - BACKGROUND: In fawn-hooded hypertensive (FHH) rats, a model of hypertension, impaired preglomerular resistance, hyperfiltration, and progressive renal injury, we recently observed that supporting perinatal nitric oxide (NO) availability with the NO donor molsidomine persistently reduced blood pressure (BP) and ameliorated renal injury in male and female offspring. However, beneficial effects of perinatal molsidomine treatment were more pronounced in female than in male FHH rats. METHODS: To evaluate whether such protective effects could also be achieved with micronutrients, and whether the gender-dependent differences could be confirmed, we tested perinatal exposure to the micronutrients L-arginine, taurine, vitamin C, and vitamin E (ATCE) in FHH rats. Perinatal micronutrients increased urinary NO metabolite, sodium and potassium excretion only at 4 weeks of age, i.e., at the end of treatment. RESULTS: From 12 weeks onwards, control males had a significantly higher systolic BP (SBP) than females (P < 0.01); however after perinatal micronutrients, this difference was no longer present, indicating a pronounced antihypertensive effect of perinatal micronutrients in males (interaction P < 0.001). Development of proteinuria was attenuated by perinatal micronutrients in males and females. However, only females showed reduced glomerular filtration rate, filtration fraction, and glomerulosclerosis (GS) after perinatal micronutrients. CONCLUSIONS: In sum, perinatal micronutrients that enhance NO availability ameliorated development of hypertension and proteinuria in FHH rats. Antihypertensive effects were more pronounced in male FHH offspring, whereas renal protective effects were more pronounced in female FHH offspring. Mechanisms underlying gender-specific consequences of perinatal micronutrients require further study. PMID- 20360752 TI - Upregulation of AT1R and iNOS in the rostral ventrolateral medulla (RVLM) is essential for the sympathetic hyperactivity and hypertension in the 2K-1C Wistar rat model. AB - BACKGROUND: We hypothesized that upregulation of angiotensin type 1 receptor (AT(1)R) and inducible nitric oxide (NO) synthase (iNOS) within the rostral ventrolateral medulla (RVLM) could contribute to two-kidney, one-clip (2K-1C) hypertension. METHODS: The experiments were performed in male Wistar rats, 6 weeks after the renal surgery. The animals were divided into control (SHAM, n = 18) and hypertensive groups (2K-1C, n = 18). Bilateral tissue punches were taken from sections containing the RVLM to perform iNOS gene expression analyses by the real-time PCR technique, and AT(1)R and iNOS protein expression analyses by western blotting. In addition, we injected losartan (1 nmol), an AT(1)R antagonist, and aminoguanidine (250 pmol), an iNOS inhibitor, bilaterally into the RVLM to analyze the mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA). RESULTS: iNOS mRNA expression levels were greater (P < 0.05) in the 2K-1C group compared to the SHAM group. Furthermore, the AT(1)R and iNOS protein expression were significantly increased in the RVLM of 2K-1C rats compared to SHAM rats. Injection of losartan into the RVLM reduced the MAP (11%) and rSNA (18%) only in the 2K-1C rats, whereas injection of aminoguanidine in the same region decreased the MAP (31%) and rSNA (34%) in hypertensive rats. CONCLUSIONS: The present study suggests that upregulation of AT(1)R and iNOS in the RVLM is important in the maintenance of high blood pressure and renal sympathetic activation in 2K-1C hypertension. PMID- 20360753 TI - Implementation of adherence support for patients with hypertension despite antihypertensive therapy in general practice: a cluster randomized trial. AB - BACKGROUND: Uncontrolled hypertension despite treatment is highly prevalent among hypertension patients. Electronic monitoring of medication adherence has been proven to be effective in improving blood pressure. The aim of the study was to compare the effectiveness of intensive support for implementation of this tool in community pharmacies with minimal implementation support. METHODS: In a cluster randomized trial, 25 control pharmacies received a manual and 32 experimental pharmacies received intensive support to enhance implementation of electronic monitoring. PRIMARY OUTCOME: the number of patients included for electronic monitoring. Secondary outcomes included mean change in systolic blood pressure (SBP) and percentage of patients with adequate SBP control. RESULTS: The experimental group yielded consistently higher scores on all the steps of the implementation process than the control group, but none of these differences were significant. The mean number of patients per pharmacy included for electronic monitoring in a 3-9-months period was 1.6 in the experimental group vs. 1.0 in the control group (difference = 0.7, 95% confidence interval = -0.4; 1.7). The following patient outcomes were pooled because there were no differences between the experimental and the control group. Mean change of SBP/diastolic blood pressure (DBP) was -12 and -6 mm Hg, respectively, SBP dropped <140 mm Hg in 20.9% of all patients. In 13.6% of all patients control of SBP was achieved without treatment intensification. CONCLUSION: The intensive implementation program enhanced pharmacist performance, but appeared insufficient to overcome all problems with the implementation of electronic monitoring. The major restrictive factors concerned general practitioner (GP) involvement and the identification of eligible patients. PMID- 20360754 TI - Cold-induced adaptive thermogenesis in lean and obese. AB - On entering a cold environment, people react by increasing insulation and energy expenditure (EE). However, large interindividual differences exist in the relative contribution of each mechanism. Short-term studies revealed that obese subjects increase EE (i.e., adaptive thermogenesis) less than lean subjects, which might have implications for the predisposition to obesity. In this study, we validate the differences in adaptive thermogenesis between lean and obese upon midterm mild cold exposure. Therefore, 10 lean and 10 obese subjects were exposed for 48 h to mild cold (16 degrees C) in a respiration chamber. The preceding 36 h they stayed in the same chamber at a neutral temperature (22 degrees C) for the baseline measurements. EE, physical activity, skin temperature, and core temperature have been measured for the last 24 h of both parts. Mean daytime EE increased significantly in the lean subjects (P < 0.01), but not in the obese. Physical activity decreased significantly in the lean (P < 0.01) and the obese (P < 0.001) subjects. The change in EE was related to the change in physical activity in both groups (respectively R(2) = 0.673, P < 0.01 and R(2) = 0.454, P < 0.05). Upon mild cold exposure, lean subjects decreased proximal skin temperature less, but distal skin temperature more than obese. In conclusion, the interindividual differences in cold-induced thermogenesis were related to changes in physical activity in both lean and obese, pointing at the existence of individual variation in physical activity to compensate for cold-induced thermogenesis. Furthermore, although a large part of the lean subjects counteracted the cold by increasing EE, most obese subjects changed temperature distribution, and therefore, increased insulation. PMID- 20360755 TI - Neighborhood socioeconomic status in relation to 10-year weight gain in the Black Women's Health Study. AB - We prospectively assessed the association of neighborhood socioeconomic status (SES) with 10-year weight change and with incident obesity among 48,359 women in the Black Women's Health Study (BWHS). Lower neighborhood SES was significantly associated with 10-year weight gain after adjustment for individual SES and behavioral variables, such as physical activity and caloric intake. Low neighborhood SES was also associated with increased incidence of obesity during 10 years of follow-up among women of normal weight at baseline (BMI <25 kg/m(2)). The associations were most evident among BWHS participants who had graduated from college. These prospective data suggest that lower neighborhood SES contributes to overweight and obesity in African-American women. PMID- 20360756 TI - The effect of obesity and weight loss on aortic pulse wave velocity as assessed by magnetic resonance imaging. AB - Obesity is an escalating global health problem associated with both an increased risk of death and an increased risk of cardiovascular events. Our goal was to use magnetic resonance imaging (MRI) to determine the effect of obesity and weight loss, in the absence of the traditional cardiovascular risk factors, on aortic pulse wave velocity (PWV) a reliable, reproducible, and accurate clinical measure of aortic stiffness linked to increased mortality. Fifty obese (BMI 38.3 +/- 6.8 kg/m(2)) and eighteen normal-weight controls (BMI 22.0 +/- 1.7 kg/m(2)) with no identifiable cardiovascular risk factors underwent vascular MRI to assess PWV between the ascending aorta at the level of the pulmonary artery and the abdominal aorta (AA). Twenty-eight subjects underwent repeat imaging after a 1 year period of weight loss. Both groups were well matched for age, systolic blood pressure, fasting glucose, and total cholesterol. Obesity was associated with a 14% increase in PWV (P = 0.021), and with elevated C-reactive protein (CRP) (P < 0.01) and leptin levels (P < 0.001) factors known to cause increase arterial stiffness. Weight loss (average 50% excess weight) was associated with a 14% improvement in PWV (P = 0.03), and with reductions in serum leptin levels (P < 0.01). Obesity, in the absence of the traditional cardiovascular risk factors, is associated with increased aortic PWV, a noninvasive clinical measure of aortic stiffness independently predictive of cardiovascular mortality. Significant weight loss results in improvements in aortic PWV. This may provide a potential link between both obesity and increased mortality, and the reduction in mortality that occurs with weight loss. PMID- 20360757 TI - Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI. AB - Abdominal fat, and in particular, visceral adipose tissue (VAT), is the critical fat depot associated with metabolic aberrations. At present, VAT can only be accurately measured by computed tomography or magnetic resonance imaging (MRI). This study was designed to compare a new abdominal bioelectrical impedance (BIA) device against total abdominal adipose tissue (TAAT) and VAT area measurements made from an abdominal MRI scan, and to assess its reliability and accuracy. One hundred twenty participants were recruited, stratified by gender and BMI. Participants had triplicate measures of abdominal fat and waist circumference (WC) with the AB-140 (Tanita, Tokyo, Japan) and WC measurements using a manual tape measure. A single abdominal MRI scan was performed as the reference method. Triplicate measures with the AB-140 showed excellent precision for "visceral fat level," trunk fat %, and WC. AB-140 "visceral fat level" showed significantly stronger correlations with MRI TAAT area than with MRI VAT area (r = 0.94 vs. 0.65 in men and 0.92 vs. 0.64 in women). AB-140 WC showed good correlation with manual WC measurements (r = 0.95 in men and 0.90 in women). AB-140 and manual WCs showed comparable correlations with MRI TAAT area (r = 0.92 and 0.96 in men and 0.88 and 0.88 in women). AB-140 is a simple, quick, and precise technique to measure abdominal fat and WC in healthy adults. It provides a useful proxy for TAAT measured by MRI, comparable to the correlation obtained with manual WC measurements. Neither the AB-140 abdominal fat measures nor WC measurement appear to provide a useful proxy measure of VAT. PMID- 20360758 TI - Adiposity in childhood is related to C-reactive protein and adiponectin in young adulthood: from the Bogalusa Heart Study. AB - To determine the association between cardiovascular (CV) risk factors in childhood and high-sensitivity C-reactive protein (hsCRP) and adiponectin in adulthood, 835 eligible white and African-American young adult subjects (age range 24-42 years, average 34 years, 43% men, 31% African Americans) who had CV risk-factor variable data from their childhood (20 years earlier, age range 5-18 years, average 14 years) were selected. Stepwise linear regression models revealed that mean logarithmic hsCRP level in adulthood was 0.02 greater with every increase of 1 mm in skinfold thickness in childhood, 0.25 greater for African Americans than whites, 0.36 greater for girls than boys, and 0.15 greater for every unit increase in BMI z score. Mean logarithmic adiponectin level in adulthood was 0.36 greater for girls than boys, 0.22 greater for whites than African Americans, and 0.01 less with every increase of 1 mm of childhood skinfold thickness. Seventy participants (8%) were overweight or obese in their childhood, and 64 of these (91%) remained obese in their young adulthood. In conclusion, childhood adiposity and African-American race were associated with higher hsCRP and lower adiponectin levels in their adulthood. Skinfold thickness and BMI z score in childhood were the main obesity determinants for higher hsCRP and lower adiponectin levels in young adulthood. PMID- 20360759 TI - Markers of inflammation and weight change in middle-aged adults: results from the prospective MONICA/KORA S3/F3 study. AB - We investigated associations of markers of inflammation such as albumin, fibrinogen, C-reactive protein (CRP), and white blood cell count (WBCC) with future weight gain and weight loss in middle-aged adults in order to further elucidate the relationship between subclinical inflammation and weight change. Data were derived from the third population-based MONICA (Monitoring of Trends and Determinants in Cardiovascular Diseases) Augsburg survey (S3) conducted as part of the multinational World Health Organization MONICA project in 1994-1995 and a follow-up examination, to which all eligible subjects from S3 were invited in 2004-2005 (F3). In total, 2,792 persons (1,391 men, 1,401 women) aged 25-74 years at baseline were analyzed. Subjects with elevated concentrations of inflammatory markers were more prone to gain weight during follow-up. The odds ratios (OR) for a large mean annual weight gain (i.e., on average 1.02 kg/year) was 1.73 (95% confidence interval (CI) 1.27, 2.35) in fully adjusted analyses for subjects in the highest compared to the lowest quartile of fibrinogen. The respective ORs were 1.45 (95% CI, 1.08, 1.94) and 1.37 (95% CI, 1.03, 1.82) for CRP and WBCC. Stratified analyses revealed that associations were strongest among subjects who quitted smoking during the follow-up period (new quitters). Associations of inflammatory markers with large mean annual weight loss were weaker and became nonsignificant after multivariable adjustment. In conclusion, elevated levels of inflammatory markers are independently associated with weight gain in middle-aged adults, particularly among new quitters. This suggests that inflammation plays a key role in the process of weight gain, especially after smoking cessation. PMID- 20360760 TI - Urinary C-peptide excretion: a novel alternate measure of insulin sensitivity in physiological conditions. AB - Insulin sensitivity (IS) is measured by the euglycemic-hyperinsulinemic clamp under a nonphysiological condition. Daily C-peptide urinary excretion may be a physiological index of IS, because C-peptide is co-secreted with insulin as a function of nutrient intake and IS. The amount of (2)H(2)O released from glycolytic glucose metabolism after [6,6-(2)H(2)]-glucose ingestion was recently proposed as a physiological measure of IS. We compared these IS surrogates to the gold standard (euglycemic-hyperinsulinemic clamp). Thirty (15 male/15 female) sedentary, nondiabetic participants (27.2 +/- 4.0 (s.d.) kg/m(2), 35 +/- 12 years) were admitted for 3 days to our in-patient unit. After a 10-h fast, they received 60 g of glucose and 15 g of [6,6-(2)H(2)]-glucose. Before glucose ingestion and hourly thereafter for 4 h, plasma glucose and insulin concentrations, and plasma deuterium enrichment were determined. Plasma (2)H(2)O production divided by insulin response was used as the glycolytic index. On day 2, subjects spent 23 h in a metabolic chamber (eucaloric diet, 50% carbohydrate, 30% fat). Urinary C-peptide excretion was divided by energy intake yielding the C peptide to energy intake ratio (CPEP/EI). After leaving the chamber (day 3, 10-h fast), IS was measured by a 2-h clamp (120 mU/m(2)/min). Average IS (clamp) was 7.3 +/- 2.6 mg glucose/kg estimated metabolic body size/min (range: 3.6-13.2). These values were inversely correlated with CPEP/EI (r = -0.62; P < 0.01) and positively with the glycolytic rate (r = 0.60; P < 0.01). In nondiabetic subjects, two novel estimates of IS--daily urinary C-peptide urinary excretion and glycolytic rate during an oral glucose tolerance test --were related to IS by a clamp. PMID- 20360761 TI - Quantitative electron microscopy for the nanoscale analysis of membrane lipid distribution. AB - An important goal of membrane biology is to define the local heterogeneity of membrane lipid composition. Here we describe a quantitative electron microscopic method that enables the localization of specific membrane lipids at the nanometer scale. The method involves freezing cells rapidly to halt the molecular motion, physically stabilizing membrane molecules in the freeze-fracture replica by the deposition of evaporated platinum and carbon layers and labeling with specific probes for electron microscopic observation. Lipids in both the outer and inner membrane leaflets can thus be labeled, and their distributions can be analyzed quantitatively by statistical methods. A major advantage of this method is that it does not require the expression of artificial probes. Therefore, this method can be applied to any cell in vitro or in vivo, and the whole procedure can be completed in 1-2 d. PMID- 20360762 TI - Measurement of the mechanical behavior of yeast membrane sensors using single molecule atomic force microscopy. AB - In Saccharomyces cerevisiae, surface stresses acting on the cell wall or plasma membrane are detected by a group of five membrane sensors: Wsc1, Wsc2, Wsc3, Mid2 and Mtl2. Here we present protocols to measure the mechanical properties of Wsc1 sensors in their native cellular environment, using the combination of genetic manipulations with single-molecule atomic-force microscopy (AFM). We describe procedures (i) for obtaining genetically modified sensors that are fully functional and suitable for AFM analysis, i.e., elongated Wsc1 derivatives terminated with a His-tag, and (ii) for detecting and stretching single Wsc1 sensors on the surface of living S. cerevisiae cells, using AFM tips functionalized with Ni(2+)-NTA groups. These procedures are multidisciplinary to implement and need competent researchers from at least two disciplines: molecular biology and nanotechnology. For experienced researchers in biological AFM, the entire protocol can be completed in approximately 3 weeks. PMID- 20360763 TI - ISH-IEM: a sensitive method to detect endogenous mRNAs at the ultrastructural level. AB - This protocol describes the combination of in situ hybridization (ISH) with cryo immunolabeling methods to allow the simultaneous detection at the ultrastructural level of mRNAs and proteins. The procedure consists of five steps and takes 4-5 d: (i) acquisition of ultrathin frozen sections of chemically fixed tissues or cells; (ii) hybridization of the sections with digoxigenin (DIG) or biotin labeled RNA probes; (iii) detection of the bound probe with antibodies and protein A-gold (PAG); (iv) labeling of proteins of interest (optional); and (v) visualization by transmission electron microscopy (immuno-electron microscopy (IEM)). This technique allows the simultaneous detection of endogenous/overexpressed/injected RNAs and proteins while preserving the cell ultrastructure. The protocol is also suitable for mRNA detection on semi-thin frozen sections in combination with immunofluorescence. The localization of targeted transcripts, such as gurken and oskar mRNA in the Drosophila oocyte, and of structural elements and proteins that mediate their localization have been revealed using this technique. PMID- 20360764 TI - Derivation of neural crest cells from human pluripotent stem cells. AB - Human pluripotent stem cell (hPSC)-derived neural crest (NC) cells present a valuable tool for modeling aspects of human NC development, including cell fate specification, multipotency and cell migration. hPSC-derived NC cells are also suitable for modeling human disease and as a renewable cell source for applications in regenerative medicine. Here we provide protocols for the step wise differentiation of human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into neuroectodermal and NC cells using either the MS5 coculture system or a novel defined culture method based on pharmacological inhibition of bone morphogenetic protein and transforming growth factor-beta signaling pathways. Furthermore, we present protocols for the purification and propagation of hPSC-NC cells using flow cytometry and defined in vitro culture conditions. Our protocol has been validated in multiple independent hESC and hiPSC lines. The average time required for generating purified hPSC-NC precursors using this protocol is 2-5 weeks. PMID- 20360765 TI - Isolation, cultivation and characterization of adult murine prostate stem cells. AB - The successful isolation and cultivation of prostate stem cells will allow us to study their unique biological properties and their application in therapeutic approaches. Here we describe step-by-step procedures on the basis of previous work in our laboratory for the harvesting of primary prostate cells from adolescent male mice by a modified enzymatic procedure; the isolation of an enriched population of prostate stem cells through cell sorting; and the cultivation of prostate stem cells in vitro and characterization of these cells and their stem-like activity, including in vivo tubule regeneration. Normally, it will take approximately 8 h to harvest prostate cells, isolate the stem cell enriched population and set up the in vitro sphere assay. It will take up to 8 weeks to analyze the unique properties of the stem cells, including their regenerative capacity in vivo. PMID- 20360766 TI - Probing localized neural mechanotransduction through surface-modified elastomeric matrices and electrophysiology. AB - Mechanotransduction of sensory neurons is of great interest to the scientific community, especially in areas such as pain, neurobiology, cardiovascular homeostasis and mechanobiology. We describe a method to investigate stretch activated mechanotransduction in sensory nerves through subcellular stimulation. The method imposes localized mechanical stimulation through indentation of an elastomeric substrate and combines this mechanical stimulation with whole-cell patch clamp recording of the electrical response to single-nerve stretching. One significant advantage here is that the neurites are stretched with limited physical contact beyond their attachment to the polymer. When we imposed specific mechanical stimulation through the substrate, the stretched neurite fired and an action potential response was recorded. In addition, complementary protocols to control the molecules at the cell-substrate interface are presented. These techniques provide an opportunity to probe neurosensory mechanotransduction with a defined substrate, whose physical and molecular context can be modified to mimic physiologically relevant conditions. The entire process from fabrication to cellular recording takes 5 to 6 d. PMID- 20360767 TI - I-TASSER: a unified platform for automated protein structure and function prediction. AB - The iterative threading assembly refinement (I-TASSER) server is an integrated platform for automated protein structure and function prediction based on the sequence-to-structure-to-function paradigm. Starting from an amino acid sequence, I-TASSER first generates three-dimensional (3D) atomic models from multiple threading alignments and iterative structural assembly simulations. The function of the protein is then inferred by structurally matching the 3D models with other known proteins. The output from a typical server run contains full-length secondary and tertiary structure predictions, and functional annotations on ligand-binding sites, Enzyme Commission numbers and Gene Ontology terms. An estimate of accuracy of the predictions is provided based on the confidence score of the modeling. This protocol provides new insights and guidelines for designing of online server systems for the state-of-the-art protein structure and function predictions. The server is available at http://zhanglab.ccmb.med.umich.edu/I TASSER. PMID- 20360768 TI - Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine. AB - The positron emitter zirconium-89 ((89)Zr) has very attractive properties for positron emission tomography (PET) imaging of intact monoclonal antibodies (mAbs) using immuno-PET. This protocol describes the step-by-step procedure for the facile radiolabeling of mAbs or other proteins with (89)Zr using p isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS). First, Df-Bz-NCS is coupled to the lysine-NH(2) groups of a mAb at pH 9.0 (pre-modification), followed by purification using gel filtration. Next, the pre-modified mAb is labeled at room temperature by the addition of [(89)Zr]Zr-oxalic acid solution followed by purification using gel filtration. The entire process of pre-modification, radiolabeling and purification steps will take about 2.5 h. PMID- 20360770 TI - Reconstitution of the cell cycle-regulated Golgi disassembly and reassembly in a cell-free system. AB - The Golgi apparatus undergoes extensive disassembly during mitosis and reassembly in post-mitotic daughter cells. This process has been mimicked in vitro by treating Golgi membranes with mitotic and interphase cytosol. To determine the minimal machinery that controls the morphological change, we have developed a defined Golgi disassembly and reassembly assay that reconstitutes this process using purified proteins instead of cytosol. Treatment of Golgi membranes with mitotic kinases and COPI coat proteins efficiently disassembles the membranes into mitotic Golgi fragments, whereas further incubation with p97 or N ethylmaleimide-sensitive factor (two AAA ATPases involved in membrane fusion) and their cofactors, in combination with protein phosphatase PP2A, leads to reassembly of the membranes into new Golgi stacks. The whole process takes 3-4 d and is applicable for identification and determination of novel cytosolic and membrane proteins that regulate Golgi membrane dynamics in the cell cycle. PMID- 20360769 TI - Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy. AB - We describe the use of transmission electron microscopy (TEM) for cellular ultrastructural examination of nanoparticle (NP)-exposed biomaterials. Preparation and imaging of electron-transparent thin cell sections with TEM provides excellent spatial resolution (approximately 1 nm), which is required to track these elusive materials. This protocol provides a step-by-step method for the mass-basis dosing of cultured cells with NPs, and the process of fixing, dehydrating, staining, resin embedding, ultramicrotome sectioning and subsequently visualizing NP uptake and translocation to specific intracellular locations with TEM. In order to avoid potential artifacts, some technical challenges are addressed. Based on our results, this procedure can be used to elucidate the intracellular fate of NPs, facilitating the development of biosensors and therapeutics, and provide a critical component for understanding NP toxicity. This protocol takes approximately 1 week. PMID- 20360771 TI - Quantifying protein-protein interactions in high throughput using protein domain microarrays. AB - Protein microarrays provide an efficient way to identify and quantify protein protein interactions in high throughput. One drawback of this technique is that proteins show a broad range of physicochemical properties and are often difficult to produce recombinantly. To circumvent these problems, we have focused on families of protein interaction domains. Here we provide protocols for constructing microarrays of protein interaction domains in individual wells of 96 well microtiter plates, and for quantifying domain-peptide interactions in high throughput using fluorescently labeled synthetic peptides. As specific examples, we will describe the construction of microarrays of virtually every human Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain, as well as microarrays of mouse PDZ domains, all produced recombinantly in Escherichia coli. For domains that mediate high-affinity interactions, such as SH2 and PTB domains, equilibrium dissociation constants (K(D)s) for their peptide ligands can be measured directly on arrays by obtaining saturation binding curves. For weaker binding domains, such as PDZ domains, arrays are best used to identify candidate interactions, which are then retested and quantified by fluorescence polarization. Overall, protein domain microarrays provide the ability to rapidly identify and quantify protein-ligand interactions with minimal sample consumption. Because entire domain families can be interrogated simultaneously, they provide a powerful way to assess binding selectivity on a proteome-wide scale and provide an unbiased perspective on the connectivity of protein-protein interaction networks. PMID- 20360772 TI - Modular system for the construction of zinc-finger libraries and proteins. AB - Engineered zinc-finger transcription factors (ZF-TF) are powerful tools to modulate the expression of specific genes. Complex libraries of ZF-TF can be delivered into cells to scan the genome for genes responsible for a particular phenotype or to select the most effective ZF-TF to regulate an individual gene. In both cases, the construction of highly representative and unbiased libraries is critical. In this protocol, we describe a user-friendly ZF technology suitable for the creation of complex libraries and the construction of customized ZF-TFs. The new technology described here simplifies the building of ZF libraries, avoids PCR-introduced bias and ensures equal representation of every module. We also describe the construction of a customized ZF-TF that can be transferred to a number of expression vectors. This protocol can be completed in 9-11 d. PMID- 20360774 TI - Coming to grips with chronic kidney disease. PMID- 20360773 TI - Generation of induced pluripotent stem cells from human cord blood cells with only two factors: Oct4 and Sox2. AB - Induced pluripotent stem cells (iPSC) provide an invaluable resource for regenerative medicine as they allow the generation of patient-specific progenitors with potential value for cell therapy. However, in many instances, an off-the-shelf approach is desirable, such as for cell therapy of acute conditions or when the patient's somatic cells are altered as a consequence of a chronic disease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are young cells expected to carry minimal somatic mutations and possess the immunological immaturity of newborn cells; additionally, several hundred thousand immunotyped CB units are readily available through a worldwide network of CB banks. Here we present a detailed protocol for the derivation of CB stem cells and how they can be reprogrammed to pluripotency by retroviral transduction with only two factors (OCT4 and SOX2) in 2 weeks and without the need for additional chemical compounds. PMID- 20360775 TI - Implication of using estimated glomerular filtration rate (GFR) in a multi ethnic population of diabetes patients in general practice. AB - AIM: To estimate the prevalence of chronic kidney disease (CKD) among diabetes patients in New Zealand, using estimated Glomerular filtration rate (eGFR); to measure the agreement between the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations in identifying CKD among Europeans and Maori; to review the metabolic control and treatment in patients with evidence of CKD. METHOD: Diabetes patients were identified though general practice records of diagnosis codes, diabetes annual reviews, prescriptions and laboratory results. The MDRD and CG equations were used to calculate the eGFR. Agreement between the two equations was expressed using Kappa statistics and was tested using McNemar's chi-square test. Logistic regression model was used to identify the predictors of CKD (eGFR<60 ml/min/1.73m2). RESULTS: Overall prevalence of CKD among diabetes patients was 19.5% (MDRD) and 23.5% (CG). Maori were significantly more likely to have CKD [Odds-ratio 1.8(1.2-2.8)]. There were significant differences between the MDRD and the CG equations in identifying patients with CKD. While CG equation identifies more European of both genders, more Maori females were identified by MDRD. CONCLUSION: Patients with decreased eGFR who do not have proteinuria or microalbuminuria might benefit from more intensive management of blood pressure. MDRD equation may be overestimating CKD among Maori females. Each ethnic subpopulation may need to be validated separately, and by gender. PMID- 20360776 TI - Ethnic disparities in causes of death among diabetes patients in the Waikato region of New Zealand. AB - AIM: Assist health service planning by: (1) estimating the causes and disparities in mortality among people with diabetes in Waikato and (2) examining the differences in recording of diabetes. METHOD: A retrospective cohort study of diabetes patients registered with the Waikato Regional Diabetes Service. Deaths from 2003-2007 were identified among patients diagnosed with diabetes before 2003. Causes of death were obtained from the NZHIS. Mortality rates were compared with the general New Zealand population. Cox's proportional-hazards-model was used to estimate the all-cause and cause-specific mortality risk. RESULTS: 921 deaths were observed among 9043 diabetes patients. Compared with Europeans, Maori had nearly double the age-adjusted mortality rates. SMRs for male-Europeans, female-Europeans, male-Maori and female-Maori aged 25+ were 1.16 (1.05-1.28), 1.10 (0.98-1.24), 2.49 (2.06-3.01), 3.12 (2.56-3.80) respectively. Of the 441 deaths with causes available, 268 (61%) had diabetes mentioned on the NZHIS coding. Maori were more likely than Europeans to have diabetes reported on NZHIS coding. They were more likely to die from cardiovascular disease, cancer and renal disease [Hazard-ratios 2.31 (1.6-3.3), 1.83 (1.1-3), and 11.74 (4.8-29) respectively]. CONCLUSION: Maori diabetes patients experienced significantly higher risk of mortality compared with Europeans. Studies on diabetes related mortality using the national mortality database needs to take the increased recognition of diabetes on NZHIS coding for Maori into account. PMID- 20360777 TI - Exploring physical and psychological wellbeing among adults with Type 2 diabetes in New Zealand: identifying a need to improve the experiences of Pacific peoples. AB - AIMS: This study explores levels of physical and psychological wellbeing among adults with Type 2 diabetes, and aims to identify the clinical, demographic, and psychological factors that are associated with differences in wellbeing. METHODS: Research participants (N=615) were randomly selected from a database of primary care records for people with diabetes (N=4857) in New Zealand. Self-report data were collected through a mailed questionnaire and clinical data from electronic records were obtained with participants' permission. RESULT: Mean HbA1c was 7.5% (SD=1.5) although this varied significantly across ethnic groups (p=.001) with metabolic control highest among New Zealand Europeans and lowest among Pacific peoples. Results showed that Pacific groups also experienced the highest levels of distress about diabetes, and concern about prescribed medication. CONCLUSIONS: Adults with Type 2 diabetes who are young, overweight, have concerns about prescribed medications, and those of Pacific ethnicity, are most likely to experience adverse health outcomes including poor metabolic control and diabetes related distress. Among Pacific peoples in particular there is a need to address concerns about medication and emotional distress about diabetes, while maintaining a focus on improving metabolic control. PMID- 20360778 TI - Standardisation of reporting haemoglobin A1c: adoption of the New Zealand Society for the Study of Diabetes (NZSSD) position statement. PMID- 20360779 TI - How well does routine hospitalisation data capture information on comorbidity in New Zealand? AB - AIMS: This study aims to assess the quality of routinely collected comorbidity data in New Zealand which are increasingly used in health service planning and research. METHODS: Detailed medical notes-based comorbidity data from a cohort study of New Zealanders diagnosed with colon cancer in 1996-2003, were compared with routine hospital discharge data collected from the same patients using 1 year and 8-year lookback periods. We compared agreement between data sources for individual conditions, Charlson comorbidity index scores and total comorbidity counts using McNemar's p-test and the kappa statistic. We also assessed the association of comorbidity with all-cause survival using Cox proportional hazard models using data ascertained from the two sources. RESULTS: Among these 569 patients, we found generally higher comorbidity was measured from notes than administrative data, with better comparability with an 8-year lookback period. Regardless of source of data, all measures of comorbidity significantly improved the ability of multivariable models to explain all-cause survival, but using both data sources combined resulted in better risk adjustment than either source separately. CONCLUSION: While differences in medical notes and administrative comorbidity data exist, the latter provides a reasonably useful source of accessible information on comorbidity for risk adjustment particularly in multivariable models. PMID- 20360780 TI - A population-based approach to the estimation of diabetes prevalence and health resource utilisation. AB - AIM: This study estimated diabetes prevalence and utilisation of healthcare services in Counties Manukau using routinely collected administrative data and compared estimates with findings for three other district health boards (DHBs) in close geographic proximity. METHOD: Records of subsidy claims for pharmaceuticals and laboratory investigations were linked to records in a national hospital admissions database to 'reconstruct' populations of four DHBs--Counties Manukau, Northland, Waitemata and Auckland. Individuals were included in reconstructed populations if they had health events recorded between January 2006 and December 2007. Diabetes cases were identified using an algorithm based on claims for monitoring tests and pharmaceuticals, as well as clinical codes for diabetes in hospital admissions. RESULTS: Reconstructed populations were only 6% lower than census population counts indicating that the vast majority of the population use health services in a two year period. The age- and sex-standardised prevalence of diabetes was 7.1% in Counties Manukau and 5.2% in the other three DHBs combined. Prevalence of diabetes was highest amongst Maori (10.6% in women and 12.2% in men) and Pacific peoples (15.0% for women and 13.5% for men). Maori diabetes cases had the highest hospital discharge rate of any ethnic group. Community pharmaceutical prescribing patterns and laboratory test frequency were similar between diabetes cases by ethnicity and deprivation. CONCLUSION: Estimates of diabetes prevalence using linkage of routinely collected administrative data were consistent with epidemiological surveys, suggesting that linkage of pharmaceutical and laboratory subsidy databases with hospital admissions data can be used as an alternative to traditional surveys for estimating the prevalence of some long-term conditions. This study demonstrated substantial differences in the prevalence of diabetes and in hospitalisation rates by ethnicity, but measures of community diabetes care were similar by ethnicity and deprivation. PMID- 20360781 TI - Capillary glucose meter accuracy and sources of error in the ambulatory setting. AB - Hand-held glucose meters are used throughout the health system by both patients with diabetes and also by health care practitioners. Glucose meter technology is constantly evolving. The current generation of meters and strips are quick to use and require a very small volume of blood. This review aims to describe meters currently available in New Zealand, for use in the ambulatory setting. It also aims to discuss the limits of meter performance and provide technical information that is relevant to the clinician, using locally available data. Commoner causes and consequences of end-user (patient and health professional) error are illustrated using clinical case examples. No meter offers definite advantages over other meters in all clinical situations, rather meters should be chosen because they fit the needs of individual patients and because the provider is able to offer appropriate educational and quality assurance backup to the meter user. A broad understanding of the advantages and disadvantages of the subsidised meter systems available in New Zealand will help the health practitioner decide when it is in the best interests of their patients to change or update meter technology. PMID- 20360782 TI - Prasugrel, Maori, and personalised medicine in New Zealand. AB - The response to thienopyridine antiplatelet therapy is heterogeneous and is in part explained by clinical and genetic factors. A recent meta-analysis has demonstrated the clinical significance of a genetic polymorphism in the cytochrome P450 2C19 gene. Carriers of this polymorphism have a higher incidence of stent thrombosis and cardiovascular death, whilst on the thienopyridine clopidogrel. The polymorphism and rarer variants display higher carrier frequencies in ethnic groups with disproportionate cardiovascular mortality, such as Maori. Knowledge of an individual's genetic status may assist in optimising antiplatelet therapy, thereby reducing the cost of adverse events, expenditure on new medicines, and the ethnic disparities seen in healthcare outcomes. A demonstration of the cost-effectiveness of genetic testing, on a population basis, and a proven alternative, personalised strategy is required before the adoption of this technology can be advocated. PMID- 20360783 TI - Podiatry services for patients with arthritis: an unmet need. AB - Foot problems are extremely common in patients with rheumatoid arthritis (RA). There is ample evidence that foot pain, either alone or as a comorbidity, contributes significantly to disability. Despite the high prevalence of foot disease in RA, this problem is often trivialised or underappreciated. The inequity in foot health provision for patients with rheumatic disorders in New Zealand has recently been highlighted. Expertise in dealing with foot problems is often limited among healthcare professionals, and it has been argued that better integration of podiatric services into rheumatology services would be beneficial. The aim of this paper is to highlight the major issues related to foot care for patients with arthritis and provide key recommendations that should implemented to improve access to podiatric services in New Zealand. PMID- 20360784 TI - Fatty infiltration of the liver in a case of hypobetalipoproteinaemia with a novel mutation in the APOB gene. PMID- 20360785 TI - Testicular seminoma metastasis to pancreas: a rare cause of obstructive jaundice. PMID- 20360786 TI - Medical image. Calcified mass in right upper abdomen. PMID- 20360787 TI - Are doctors team players, and do they need to be? AB - Evidence suggests that teamwork failures contribute to poor outcomes in hospitals and that changes in healthcare delivery have at times worked against the development of effective healthcare teams. Doctors' engagement with the concept of healthcare teams, although variable, has generally been supportive and there have been several successful initiatives. However, lack of evidence on the critical components that improve the performance of healthcare teams impedes growth in our understanding and development of effective teams. In an endeavour to improve the function of healthcare teams through education and systems change, the psychology literature remains a useful framework for studying the critical components of team processes. PMID- 20360788 TI - Medical image. Anaemia and skeletal deformities. PMID- 20360789 TI - Reducing delay for myocardial infarction. PMID- 20360790 TI - The right diet--'sweet as'? PMID- 20360791 TI - Bariatric surgery: a dilemma for the health system? PMID- 20360792 TI - Addictive overeating: lessons learned from medical students' perceptions of Overeaters Anonymous. AB - AIM: To explore medical students' perceptions of Overeaters Anonymous (OA). METHOD: 72 fifth-year medical students' reports of their experiences of attending OA meetings were analysed using thematic analysis. Students were required to submit these reports in order to complete a compulsory component of the Addiction Medicine run in their medical training at the University of Otago, Christchurch during 2002-2007. RESULTS: Analysis of the students' reports highlights an emerging understanding of the concepts of addiction in general and addictive overeating in particular. This understanding is reflected in the students' acceptance of addictive overeating as a potential disorder and their increased empathy and confidence in working with patients with this disorder. CONCLUSIONS: Improving treatment for people with obesity is a major contemporary health challenge. Addictive overeating could be a critical element in understanding the nature of obesity but has not been the subject of extensive research to date. Medical students in this study discovered that addiction to food is not just a theoretical construct but fits with the actual experience of people. The poignancy of these narratives illustrates how such information can promote greater understanding of medical and other life issues which may benefit their identification and treatment. PMID- 20360793 TI - Ethnic-specific body mass index cut-off points for overweight and obesity in girls. AB - AIM: To develop ethnic-specific body mass index (BMI) cut-off points for overweight and obesity in girls from New Zealand's five major ethnic groups. METHODS: A total of 1676 girls (41% European, 21% Pacific Island, 15% East Asian, 13% Maori, and 11% South Asian) aged 5-16 years participated in this study. BMI was determined from height and weight, and body fat percentage (%BF) was obtained from hand-to-foot bioelectrical impedance measurements. Using stepwise multiple regression, a series of ethnic-specific BMI cut-off points were developed that corresponded to the equivalent %BF of European girls at the BMI reference values provided by the International Obesity TaskForce (IOTF). RESULTS: The adjusted cut off points for overweight and obesity ranged from an average of 3.3 and 3.8 kg.m( 2) (respectively) lower than the IOTF standards in South Asian girls to 1.5 and 1.9 kg.m(-2) higher in Pacific Island girls. CONCLUSION: We conclude that the ethnic-specific BMI cut-off points developed in this study are more appropriate than universal definitions of overweight and obesity for predicting excess adiposity in New Zealand girls. PMID- 20360794 TI - Overweight and obesity prevalence among adult Pacific peoples and Europeans in the Diabetes Heart and Health Study (DHAHS) 2002-2003, Auckland New Zealand. AB - AIM: This paper describes and compares proportions of overweight, obese, and average BMI and their relationship with physical activity for Pacific ethnic groups (Samoan, Tongan, Niue, Cook Islands) and European New Zealanders by gender who participated in the 2002-03 Diabetes Heart and Health Study (DHAHS). METHODS: The DHAHS was a cross-sectional population based study of people age 35-74 years carried out in Auckland between 2002-03. A total of 1011 Pacific people comprising of 484 Samoan, 252 Tongan, 109 Niuean, 116 Cook Islanders and 47 'Other Pacific' (mainly Fijian) and 1745 European participants took part in the survey. Participants answered a self-administered questionnaire to assess their participation in physical activity, perceived weight, and their perception of their current weight. Following this participant's height and weight was measured for calculation of BMI. Ethnic-specific cut offs were used for classification of overweight (Pacific > or = 26.0-<32.0, European > or = 25.0-<30.0) and obesity (Pacific > or = 26.0, European > or = 32.0). RESULTS: Approximately 95% of Pacific men and 100% Pacific women were 'overweight or obese'. Proportions of obesity were for men: all Pacific 53%, Samoan 58%, Cook Island 23%, Tongan 60%, and Niuean 49%; and for women: all Pacific 74%, Samoan 75%, Cook Island 69%, Tongan 78%, and Niuean 76%. Pacific people were as accurate at estimating their body weight as Europeans, and included similar proportions who under-estimated their weight. The Cook Islands group were most likely to accurately report their weight and were significantly less likely to underestimate their weight. A significantly higher proportion of Pacific people reported that they were heavier than a year ago (22.7%) compared to Europeans (17.2%), but significantly fewer Pacific people (55.6%) reported thinking that they were overweight compared to Europeans (64.9%). After adjustment for possible confounding variables, older Pacific adults were over 11 times more likely to be obese than their Europeans counterparts. CONCLUSION: The continued rise in overweight and obesity in older Pacific adults means that almost all are now overweight or obese. This raises concerns about interventions focussed on overweight and obesity, and will require the adoption of a total Pacific population 'environmental change' approach rather than dietary or physical activity interventions targeted to overweight individuals. PMID- 20360795 TI - Healthier vending machines in workplaces: both possible and effective. AB - AIM: To develop healthier vending guidelines and assess their effect on the nutrient content and sales of snack products sold through hospital vending machines, and on staff satisfaction. METHODS: Nutrition guidelines for healthier vending machine products were developed and implemented in 14 snack vending machines at two hospital sites in Auckland, New Zealand. The guidelines comprised threshold criteria for energy, saturated fat, sugar, and sodium content of vended foods. Sales data were collected prior to introduction of the guidelines (March May 2007), and again post-introduction (March-May 2008). A food composition database was used to assess impact of the intervention on nutrient content of purchases. A staff survey was also conducted pre- and post-intervention to assess acceptability. RESULTS: Pre-intervention, 16% of staff used vending machines once a week or more, with little change post-intervention (15%). The guidelines resulted in a substantial reduction in the amount of energy (-24%), total fat ( 32%), saturated fat (-41%), and total sugars (-30%) per 100 g product sold. Sales volumes were not affected, and the proportion of staff satisfied with vending machine products increased. CONCLUSIONS: Implementation of nutrition guidelines in hospital vending machines led to substantial improvements in nutrient content of vending products sold. Wider implementation of these guidelines is recommended. PMID- 20360796 TI - Aspartame--facts and fiction. PMID- 20360798 TI - Bariatric surgery: a cutting-edge cure for Type 2 diabetes? AB - Type 2 diabetes is rapidly becoming a global health crisis. It is associated with multiple comorbidities and is placing an ever increasing financial burden on society. There is now a need to explore new methods of tackling this problem. A growing pool of evidence suggests that bariatric surgery has the potential to cure Type 2 diabetes in a select population and provide additional benefits for many of its associated comorbidities. Whilst there are various proposals that explain these phenomena, current research suggests the cause is mainly due to increased post surgical release of insulin promoting gut hormones. The aim of this paper is to introduce some of the complex issues surrounding the use of bariatric surgery in Type 2 diabetes and highlight the controversial aspects encompassing this topic. PMID- 20360797 TI - The New Zealand sugar (fructose) fountain: time to turn the tide? PMID- 20360799 TI - Preoperative diagnosis of cholecystocolonic fistula on ERCP. PMID- 20360800 TI - An unusual presentation of staphylococcal tricuspid valve infective endocarditis. PMID- 20360801 TI - Medical image. A case of rhinodynia and asthma. Nose piercing. PMID- 20360802 TI - Proceedings of 'tinnitus discovery': Asia-pacific Tinnitus Symposium, 11-12 Sept 2009, Auckland, New Zealand. PMID- 20360803 TI - Australian dust causing respiratory disease admissions in some North Island, New Zealand hospitals. PMID- 20360804 TI - A new opportunity to eliminate policy incoherence in tobacco control in New Zealand. PMID- 20360805 TI - The extent of YouTube videos with smoking and smokefree words. PMID- 20360806 TI - In defence of Linda Bryder's book A history of the 'unfortunate experiment' at National Women's Hospital. PMID- 20360807 TI - The legacy of Sir Charles Hercus. PMID- 20360808 TI - Medical image. Painful foot swellings. Tophaceous gout. PMID- 20360809 TI - Debye series for light scattering by a spheroid. AB - The Debye series is developed for electromagnetic scattering by a spheroid in order to decompose the far-zone fields into various physical processes. The geometrical rainbow angle and supernumerary spacing parameter are determined from the Debye intensity by fitting the results to an Airy function and comparing them to their assumed values in ray optics and Airy theory, respectively. Eccentricity related scattering phenomena including the rainbow's angular shift, the disappearance of the rainbow, and the rainbow-enhanced glory are quantitatively demonstrated and analyzed. PMID- 20360810 TI - Scattering by dielectric circular cylinders in a dielectric slab. AB - An analytical-numerical technique for the solution of the plane-wave scattering problem by a set of dielectric cylinders embedded in a dielectric slab is presented. Scattered fields are expressed by means of expansions into cylindrical functions, and the concept of plane-wave spectrum of a cylindrical function is employed to define reflection and transmission through the planar interfaces. Multiple reflection phenomena due to the presence of a layered geometry are taken into account. Solutions can be obtained for both TM and TE polarizations and for near- and far-field regions. The numerical approach is described and the method is validated by comparison with examples given in the literature, with very good agreement. Results are presented for the scattering by a finite grid of three cylinders embedded in a slab. PMID- 20360811 TI - Fast modal method for subwavelength gratings based on B-spline formulation. AB - We present a B-spline modal method for analyzing a stack of complex structured layers. Thanks to a B-spline approximation of the field, we solve the Maxwell equations. Diffraction calculation is based on the scattering matrices algorithm. We prove a good convergence of this method. Moreover, B-spline approximation results in very sparse matrices, which are used to hasten the computation of eigenmodes. A method for cleaning the inverted sparse matrix is also presented. PMID- 20360812 TI - A comparison of modeling methods for ring resonator circuits. AB - We have previously introduced a "compound ring resonator circuit," in which several ring resonator (RR) cavities are coupled in a loop, and analyzed the resulting configuration with the coupling of modes in space (CMS) technique. In this work we compare the accuracy, simplicity and calculation time of three standard procedures, namely the FDTD, and the methods of coupling of modes in time (CMT) and CMS in the context of a two-dimensional (2D) complex ring resonator circuit. This provides a far more effective benchmark of the relative advantages of the methods than the analysis of far simpler structures performed by other authors. As part of these calculations, we further discuss the relationship between the power loss coefficients in the CMS and the CMT models. We verify that the CMT yields accurate and rapid results for small coupling coefficients and losses even for large waveguide circuits containing multiple rings. PMID- 20360813 TI - Vector wave propagation method. AB - In this paper, we extend the scalar wave propagation method (WPM) to vector fields. The WPM [Appl. Opt.32, 4984 (1993)] was introduced in order to overcome the major limitations of the beam propagation method (BPM). With the WPM, the range of application can be extended from the simulation of waveguides to simulation of other optical elements like lenses, prisms and gratings. In that reference it was demonstrated that the wave propagation scheme provides valid results for propagation angles up to 85 degrees and that it is not limited to small index variations in the axis of propagation. Here, we extend the WPM to three-dimensional vectorial fields (VWPMs) by considering the polarization dependent Fresnel coefficients for transmission in each propagation step. The continuity of the electric field is maintained in all three dimensions by an enhanced propagation vector and the transfer matrix. We verify the validity of the method by transmission through a prism and by comparison with the focal distribution from vectorial Debye theory. Furthermore, a two-dimensional grating is simulated and compared with the results from three-dimensional RCWA. Especially for 3D problems, the runtime of the VWPM exhibits special advantage over the RCWA. PMID- 20360814 TI - General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference. AB - Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices. PMID- 20360815 TI - Relative importance of sources of chromatic refractive error in the human eye. AB - The relative importance of the various optical elements of the human eye are analyzed to determine which contribute most to the chromatic variance in total refractive power of the eye. The concept of differential dispersion, defined as the change in the difference in index of refraction across a refractive surface with change in wavelength, is used to provide a theoretical tool for this analysis. The theoretical treatment shows that almost all the chromatic effect will be caused by the air-tear interface. Calculations of model eyes are made that support this view. Four model eyes are examined, an emmetropic eye, a hyperopic eye, a myopic eye, and an emmetropic eye accommodating 2.5 D. PMID- 20360816 TI - Image matching with higher-order geometric features. AB - We propose a geometric matching technique in which line segments and elliptical arcs are used as edge features. The use of these higher-order features renders feature representation efficient. We derive distance measures to evaluate the similarity between the features of the model and those of the image. The model transformation parameters are found by searching a 3-D transformation space using cell-decomposition. The performance of the proposed method is quite good when tested on a variety of images. PMID- 20360817 TI - Numerical study on a micro prism and micro lenses with metal-dielectric multilayered structures. AB - A micro optical prism and micro lenses with metal-and-dielectric multilayered subwavelength structure (MDMS) are discussed. The MDMS prism has a highly dispersive optical property. Light waves do not spread out in the small prism because of the restriction of propagation direction of light. Optical properties of a curved MDMS prism were investigated by theoretical analysis and numerical simulations. The curved MDMS prism with a structure period of 0.4 microm and an apex angle of 90 degrees had angular dispersion of 0.11 degrees /nm for light of 1.5 microm wavelength. A convexo-plane MDMS lens and a gradient-index MDMS lens were also investigated, and the optical behavior for the curved prism with the convexo-plane lens was demonstrated by a numerical simulation. PMID- 20360818 TI - Prospects of Wannier functions in investigating photonic crystal all-optical devices for signal processing. AB - Wannier functions derived from Bloch functions have been identified as an efficient means of analyzing the properties of photonic crystals in which localized functions have now opened the door for 2D and 3D structures containing defects to be investigated. In this paper, based on the Maxwell equations in diagonalized form and utilizing Bloch waves we have obtained an equivalent system of algebraic equations in eigenform. By establishing and exploiting several distinct properties of the resulting eigenpairs, we demonstrate an ability to construct Wannier functions associated with the simplest one-dimensional photonic structure. More importantly, the numerical investigation of the inner- and intra band orthonormality conditions as well as Hilbert space partitioning features shows a capability for multi-resolution analysis that will make all-optical signal processing devices with photonic crystal structures feasible. PMID- 20360819 TI - Bar-like S-cone stimuli reveal the importance of an intermediate temporal filter. AB - The relative involvement of different temporal frequency-selective filters underlying detection of chromatic stimuli was studied. Diverse spectral stimuli were used, namely flashed blue and yellow light spots, wide bars, and narrow bars. The stimuli were temporally modulated in luminance having constant wavelength. Although the bar-like stimuli apparently reduced the sensitivity at short and long wavelengths, the cone-opponent mechanism still remained responsible for the actual stimulus detection at different temporal frequencies. The bar-like stimuli increased sensitivity for temporal frequencies around 3-6 Hz, revealing involvement of an intermediate temporal frequency-selective filter in detection, the so-called transient-1 filter. A probability summation model for the method of adjustment was developed that assumes that detection depends on the properties of the temporal filters underlying the temporal frequency-sensitivity curve. The model supports the notion that at least two temporal frequency selective filters are necessary to account for the shape of the sensitivity curves obtained for blue bar-like stimuli. PMID- 20360820 TI - Application of Riesz transforms to the isotropic AM-PM decomposition of geometrical-optical illusion images. AB - The existence of a special second-order mechanism in the human visual system, able to demodulate the envelope of visual stimuli, suggests that spatial information contained in the image envelope may be perceptually relevant. The Riesz transform, a natural isotropic extension of the Hilbert transform to multidimensional signals, was used here to demodulate band-pass filtered images of well-known visual illusions of length, size, direction, and shape. We show that the local amplitude of the monogenic signal or envelope of each illusion image conveys second-order information related to image holistic spatial structure, whereas the local phase component conveys information about the spatial features. Further low-pass filtering of the illusion image envelopes creates physical distortions that correspond to the subjective distortions perceived in the illusory images. Therefore the envelope seems to be the image component that physically carries the spatial information about these illusions. This result contradicts the popular belief that the relevant spatial information to perceive geometrical-optical illusions is conveyed only by the lower spatial frequencies present in their Fourier spectrum. PMID- 20360821 TI - Mean level signal crossing rate for an arbitrary stochastic process. AB - The issue of the mean signal level crossing rate for various probability density functions with primary relevance for optics is discussed based on a new analytical method. This method relies on a unique transformation that transforms the probability distribution under investigation into a normal probability distribution, for which the distribution of mean level crossings is known. In general, the analytical results for the mean level crossing rate are supported and confirmed by numerical simulations. In particular, we illustrate the present method by presenting analytic expressions for the mean level crossing rate for various probability distributions, including ones that previously were unavailable, such as the uniform, the so-called gamma-gamma, and the Rice Nakagami distribution. However, in a limited number of cases the present results differ somewhat from the result reported in the literature. At present, this discrepancy remains unexplained and is laid open for future discussion. PMID- 20360822 TI - Alternative depolarization criteria for Mueller matrices. AB - It is shown that the currently used depolarization criteria of Gil and Bernabeu [Opt. Acta 33, 185 (1986)] and Cloude [Optik (Stuttgart) 75, 26 (1986)] may produce erroneous results when applied to a special class of Mueller matrices. Alternative criteria, based on the Lorentz singular values of the Mueller matrix, are proposed. The theory underlying the two sets of depolarization criteria is discussed and their performances on experimentally determined Mueller matrices are illustrated. PMID- 20360823 TI - Electromagnetic scattering from multiple sub-wavelength apertures in metallic screens using the surface integral equation method. AB - This work presents a novel finite-element solution to the problem of scattering from multiple two-dimensional holes with side grating in infinite metallic walls. The formulation is based on using the surface integral equation with free-space Green's function as the boundary constraint. The solution region is divided into interior regions containing each hole or cavity as a side grating and exterior region. The finite-element formulation is applied inside the interior regions to derive a linear system of equations associated with nodal field values. The surface integral equation is then applied at the opening of the holes as a boundary constraint to connect nodes on the boundaries to interior nodes. The technique presented here is highly efficient in terms of computing resources, versatile and accurate in comparison with previously published methods. The near and far fields are generated for different single and multiple hole examples. PMID- 20360824 TI - Stochastic reconstruction of anisotropic polarizabilities. AB - By solving a linear stochastic equation, we demonstrate how probability density functions of scattered intensities and order statistics can be used for reconstructing the statistical properties of fluctuating anisotropic polarizabilities. Depending on the statistical relationship between the elements of the polarizability tensor, we show how task optimized measurements can be conducted to reduce the number of necessary measurements. This approach is directly applicable to polarimetric measurements with limited control over the experimental conditions. PMID- 20360825 TI - Describing the structure of ronchigrams when the grating is placed at the caustic region: The parabolical mirror. AB - In this work we use the geometrical point of view of the Ronchi test and the caustic-touching theorem to describe the structure of the ronchigrams for a parabolical mirror when the point light source is on and off the optical axis and the grating is placed at the caustic associated with the reflected light rays. We find that for a given position of the point light source the structure of the ronchigram is determined by the form of the caustic and the relative position between the grating and the caustic. We remark that the closed loop fringes commonly observed in the ronchigrams appear when the grating and the caustic are tangent to each other. Furthermore, we find that the caustic locally has singularities of the purse or hyperbolic umbilic type, and the ronchigram obtained when the grating is located at certain specific positions at the caustic locally is of the serpentine type. The main motivation of this work is that nowadays a quantitative analysis of the Ronchi test is applied only when the grating is outside the caustic, and we claim that by working at the caustic, the sensitivity of the Ronchi test will be improved. Therefore, a clear understanding of the properties of the ronchigrams when the grating is placed at the caustic will be needed to extend the Ronchi test to that region. PMID- 20360826 TI - Surface plasmon resonance based fiber optic sensor for the IR region using a conducting metal oxide film. AB - Theoretical modeling of a surface plasmon resonance (SPR) based fiber optic sensor with a conducting metal oxide [indium tin oxide (ITO)] as the SPR active material is proposed. The theoretical analysis reveals that the proposed sensing probe can be utilized for sensing in the IR region, where most of the gases show their absorption regime. Comparison of sensitivity predicts that an ITO-layer coated SPR-based fiber optic sensor is about 60% more sensitive than a gold coated fiber optic sensor. The physical reasons behind sensitivity enhancement are provided. Apart from this, various advantageous features of the ITO over the noble metals, silver and gold, are addressed. PMID- 20360827 TI - Divisive normalization image quality metric revisited. AB - Structural similarity metrics and information-theory-based metrics have been proposed as completely different alternatives to the traditional metrics based on error visibility and human vision models. Three basic criticisms were raised against the traditional error visibility approach: (1) it is based on near threshold performance, (2) its geometric meaning may be limited, and (3) stationary pooling strategies may not be statistically justified. These criticisms and the good performance of structural and information-theory-based metrics have popularized the idea of their superiority over the error visibility approach. In this work we experimentally or analytically show that the above criticisms do not apply to error visibility metrics that use a general enough divisive normalization masking model. Therefore, the traditional divisive normalization metric 1 is not intrinsically inferior to the newer approaches. In fact, experiments on a number of databases including a wide range of distortions show that divisive normalization is fairly competitive with the newer approaches, robust, and easy to interpret in linear terms. These results suggest that, despite the criticisms of the traditional error visibility approach, divisive normalization masking models should be considered in the image quality discussion. PMID- 20360828 TI - Numerical modeling of light propagation in a hexagonal array of dielectric cylinders. AB - To model the light-guiding properties of a hexagonal array of dielectric cylinders, we have numerically solved Maxwell's equations with the finite difference time-domain technique. The sizes and refractive indices of the cylinders are representative of those of the outer segments of the cone photoreceptors in the human central retina. In the array, light propagates predominantly as a "slow" mode, with a noticeable contribution of a "fast" mode, with the optical field localized in the intra- and inter-cylinder spaces, respectively. Interference between these modes leads to substantial (up to approximately 60%) axial oscillations in optical power within the cylinders. Our numerical model offered approximate dependence of the optical intensity distribution within the cylinders on their radii and separations. PMID- 20360829 TI - Magnetically induced Mie resonance in a magnetic sphere suspended in a ferrofluid. AB - Mie scattering functions for a magnetizable sphere whose relative refractive index is dependent on the externally applied magnetic field are computed for four different sizes of the sphere. It is found that Mie resonances are observed at certain critical fields when the incident light is polarized with its electric vector perpendicular to the applied field. The width of resonance as well as the critical fields shifts with the increase in size of the spheres. Results are compared with the experimentally observed scattering effects in a dispersion of magnetite spheres in a ferrofluid. PMID- 20360830 TI - All-purpose finite element formulation for arbitrarily shaped crossed-gratings embedded in a multilayered stack. AB - We propose a novel formulation of the finite element method adapted to the calculation of the vector field diffracted by an arbitrarily shaped crossed grating embedded in a multilayered stack and illuminated by an arbitrarily polarized plane wave under oblique incidence. A complete energy balance (transmitted and reflected diffraction efficiencies and losses) is deduced from field maps. The accuracy of the proposed formulation has been tested using classical cases computed with independent methods. Moreover, to illustrate the independence of our method with respect to the shape of the diffractive object, we present the global energy balance resulting from the diffraction of a plane wave by a lossy thin torus crossed-grating. Finally, computation time and convergence as a function of the mesh refinement are discussed. As far as integrated energy values are concerned, the presented method shows a remarkable convergence even for coarse meshes. PMID- 20360831 TI - Non-paraxial investigation in the far field properties of controllable dark hollow beams diffracted by a circular aperture. AB - Based on the angular spectrum representation and the method of stationary phase, an analytically asymptotic expression of the far field of a controllable dark hollow beam (CDHB) diffracted by a circular aperture is derived. The normalized intensity distributions of an apertured CDHB in the far field are numerically demonstrated. The influence of the f-parameter on the non-paraxiality of the far field of an apertured CDHB is the largest, and the effect of the truncation parameter delta on the non-paraxiality of the far field is the smallest. The difference between the non-paraxial and the paraxial results is independent of the beam order N. The far field pattern of apertured CDHBs sometimes is only a central bright spot. Under certain conditions, a weakly brightly outer ring around the central bright spot is detected in the far field pattern. PMID- 20360832 TI - Extended active optical lattice filters: filter synthesis. AB - In this paper, we study the synthesis of asymptotically stable filters from a unit cell of a two-dimensional tunable lattice filter architecture consisting of four four-port couplers and four waveguides containing semiconductor optical amplifiers. Upper bounds on the number of gains that will produce a filter with a priori prescribed poles, for a specific system, are obtained. We also provide sufficient conditions on the reflection-type coefficients, characterizing each four-port coupler, which ensure that real-valued gains, taking values in [0,1], exist so that the filter is asymptotically stable. Finally, we motivate the notion of a transmission zero of a filter and discuss the possibility of simultaneously placing both poles and transmission zeros for the unit cell. PMID- 20360833 TI - Polarization weighting of Fano-type transmission through bi-dimensional metallic gratings. AB - We demonstrate an approach allowing isolating effects of surface plasmon polariton mediated resonant transmission in a periodic grating by means of polarization rotation. The grating comprises a square array of cylindrical holes in an optically thick metallic film. Transmittance data for the co- and cross polarized cases are described accurately with Fano-type and pure Lorentzian-type line shapes, respectively. This polarization control allows for changing the relative weights of resonant and non-resonant transmission mechanisms, thus controlling the shape and symmetry of the observed Fano-type line shapes. PMID- 20360834 TI - Signal representation on the angular Poincare sphere, based on second-order moments. AB - Based on the analysis of second-order moments, a generalized canonical representation of a two-dimensional optical signal is proposed, which is associated with the angular Poincare sphere. Vortex-free (or zero-twist) optical beams arise on the equator of this sphere, while beams with a maximum vorticity (or maximum twist) are located at the poles. An easy way is shown how the latitude on the sphere, which is a measure for the degree of vorticity, can be derived from the second-order moments. The latitude is invariant when the beam propagates through a first-order optical system between conjugate planes. To change the vorticity of a beam, a system that does not operate between conjugate planes is needed, with the gyrator as the prime representative of such a system. A direct way is derived to find an optical system (consisting of a lens, a magnifier, a rotator, and a gyrator) that transforms a beam with an arbitrary moment matrix into its canonical form. PMID- 20360835 TI - Cherenkov radiation versus X-shaped localized waves. AB - Localized waves (LW) are nondiffracting ("soliton-like") solutions to the wave equations and are known to exist with subluminal, luminal, and superluminal peak velocities V. For mathematical and experimental reasons, those that have attracted more attention are the "X-shaped" superluminal waves. Such waves are associated with a cone, so that one may be tempted-let us confine ourselves to electromagnetism-to look [Phys. Rev. Lett.99, 244802 (2007)] for links between them and the Cherenkov radiation. However, the X-shaped waves belong to a very different realm: For instance, they can be shown to exist, independently of any media, even in vacuum, as localized non-diffracting pulses propagating rigidly with a peak-velocity V>c [Hernandez et al., eds., Localized Waves (Wiley, 2008)]. We dissect the whole question on the basis of a rigorous formalism and clear physical considerations. PMID- 20360836 TI - Explicit relations and optimal parameters for sidelobe suppression in optical vortices with a modified Bessel function. AB - This paper establishes explicit relations between the radial modulation and the optimal sidelobe expression effect in the Bessel-like modulation technique. It verifies that both central and outer ring areas of the phase plate result in sidelobes in the diffraction pattern, and the corresponding structural dimensions can be determined quantitatively. This approach gives rise to complete sidelobe suppression by taking optimal modulation parameters. PMID- 20360837 TI - Constitutive expression of pluripotency-associated genes in mesodermal progenitor cells (MPCs). AB - BACKGROUND: We recently characterized a progenitor of mesodermal lineage (MPCs) from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation. METHODOLOGY/PRINCIPAL FINDINGS: MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15. CONCLUSIONS/SIGNIFICANCE: MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested from human bone marrow. PMID- 20360838 TI - In-depth transcriptome analysis reveals novel TARs and prevalent antisense transcription in human cell lines. AB - Several recent studies have indicated that transcription is pervasive in regions outside of protein coding genes and that short antisense transcripts can originate from the promoter and terminator regions of genes. Here we investigate transcription of fragments longer than 200 nucleotides, focusing on antisense transcription for known protein coding genes and intergenic transcription. We find that roughly 12% to 16% of all reads that originate from promoter and terminator regions, respectively, map antisense to the gene in question. Furthermore, we detect a high number of novel transcriptionally active regions (TARs) that are generally expressed at a lower level than protein coding genes. We find that the correlation between RNA-seq data and microarray data is dependent on the gene length, with longer genes showing a better correlation. We detect high antisense transcriptional activity from promoter, terminator and intron regions of protein-coding genes and identify a vast number of previously unidentified TARs, including putative novel EGFR transcripts. This shows that in depth analysis of the transcriptome using RNA-seq is a valuable tool for understanding complex transcriptional events. Furthermore, the development of new algorithms for estimation of gene expression from RNA-seq data is necessary to minimize length bias. PMID- 20360839 TI - In vitro interactions of extracellular histones with LDL suggest a potential pro atherogenic role. AB - BACKGROUND: Nuclear histones have previously been shown to aggregate LDL in vitro, suggestive of a possible pro-atherogenic role. Recent studies indicate that histones are released during acute inflammation, and therefore might interact with circulating lipoproteins in vivo. In view of the associative link between inflammation and cardiovascular disease, the behaviour of histones was investigated using in vitro models of LDL retention and foam cell formation. METHODOLOGY/PRINCIPAL FINDINGS: Heparin agarose beads were used as a model of a matrix rich in sulphated glycosaminoglycans, to which histones bind strongly. Histone-modified beads were observed to pull down more LDL from solution than untreated beads, indicating that histones can function as bridging molecules, enhancing LDL retention. Furthermore, addition of heparin inhibited histone induced aggregation of LDL. To model foam cell formation, murine RAW 264.7 macrophages were incubated for 24 h in the presence of LDL, histones, LDL plus histones or vehicle control. Cells incubated with LDL in the presence of histones accumulated significantly more intracellular lipid than with LDL or histone alone. CONCLUSIONS/SIGNIFICANCE: These results are consistent with a potential pro-atherogenic role for extracellular histones, which should be investigated further. PMID- 20360840 TI - HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse? AB - Exosomes are secreted cellular vesicles that can induce specific CD4(+) T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence of fusion events in search of adequate target cells. Here, we discuss recent data supporting this hypothesis, which further explains how DCs can capture and internalize retroviruses like HIV-1 in the absence of fusion events, leading to the productive infection of interacting CD4(+) T cells and contributing to viral spread through a mechanism known as trans-infection. We suggest that HIV-1 can exploit an exosome antigen-dissemination pathway intrinsic to mDCs, allowing viral internalization and final trans-infection of CD4(+) T cells. In contrast to previous reports that focus on the ability of immature DCs to capture HIV in the mucosa, this review emphasizes the outstanding role that mature DCs could have promoting trans-infection in the lymph node, underscoring a new potential viral dissemination pathway. PMID- 20360841 TI - Imaging of surfaces by concurrent surface plasmon resonance and surface plasmon resonance-enhanced fluorescence. AB - Surface plasmon resonance imaging and surface plasmon induced fluorescent are sensitive tools for surface analysis. However, existing instruments in this area have provided limited capability for concurrent detection, and may be large and expensive. We demonstrate a highly cost-effective system capable of concurrent surface plasmon resonance microscopy (SPRM) and surface plasmon resonance enhanced fluorescence (SPRF) imaging, allowing for simultaneous monitoring of reflectivity and fluorescence from discrete spatial regions. The instrument allows for high performance imaging and quantitative measurements with surface plasmon resonance, and surface plasmon induced fluorescence, with inexpensive off the-shelf components. PMID- 20360842 TI - Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy. AB - Assessment of molecular defects that underlie cognitive deficits observed in mendelian disorders provides a unique opportunity to identify key regulators of human cognition. Congenital Myotonic Dystrophy 1 (cDM1), a multi-system disorder is characterized by both cognitive deficits and a spectrum of behavioral abnormalities, which include visuo-spatial memory deficits, anxiety and apathy. Decreased levels of DMPK (Dystrophia Myotonica-protein kinase), SIX5, a transcription factor or MBNL1 (Muscleblind-like 1), an RNA splice regulator have been demonstrated to contribute to distinct features of cDM1. Mouse strains in which either Dmpk, Six5 or Mbnl1 are inactivated were therefore studied to determine the relative contribution of each gene to these cognitive functions. The open field and elevated plus maze tasks were used to examine anxiety, sucrose consumption was used to assess motivation, whereas the water maze and context fear conditioning were used to examine spatial learning and memory. Cognitive and behavioral abnormalities were observed only in Mbnl1 deficient mice, which demonstrate behavior consistent with motivational deficits in the Morris water maze, a complex visuo-spatial task and in the sucrose consumption test for anhedonia. All three models of cDM1 exhibit normal spatial learning and memory. These data identify MBNL1 as a potential regulator of emotional state with decreased MBNL1 levels underlying the motivational deficits observed in cDM1. PMID- 20360843 TI - The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. AB - Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr-64 improves the growth rate of the fat-6;fat-7and sbp-1 strains. While nhr-64RNAi subtly affects fatty acid composition and fat storage in wild-type C. elegans, its effects on lipid metabolism are most apparent in the background of stearoyl-CoA desaturase or SREBP deficiency. NHR-64 displays transcriptional activating activity when expressed in yeast, and inactivation of nhr-64 affects the expression of at least 14 metabolic genes. Wild-type worms treated with nhr-64 RNAi display increased expression of acetyl-CoA carboxylase as well as increased abundance of de novo synthesized monomethyl branched chain fatty acids, suggesting an increase in fat synthesis. However, reduced expression of the acetyl-CoA synthetase gene acs-2 and an acyl-CoA oxidase gene indicates that a key role of NHR-64 may be to promote fatty acid oxidation in mitochondria and peroxisomes. These studies reveal that NHR-64 is an important regulator of fat storage in C. elegans. PMID- 20360844 TI - Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. AB - BACKGROUND: Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome wide significance (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01). CONCLUSIONS/SIGNIFICANCE: A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study. PMID- 20360845 TI - A septin from the filamentous fungus A. nidulans induces atypical pseudohyphae in the budding yeast S. cerevisiae. AB - BACKGROUND: Septins, novel cytoskeletal proteins, form rings at the bases of emerging round buds in yeasts and at the bases of emerging elongated hyphal initials in filamentous fungi. METHODOLOGY/PRINCIPAL FINDINGS: When introduced into the yeast Saccharomyces cerevisiae, the septin AspC from the filamentous fungus Aspergillus nidulans induced highly elongated atypical pseudohyphae and spore-producing structures similar to those of hyphal fungi. AspC induced atypical pseudohyphae when S. cerevisiae pseudohyphal or haploid invasive genes were deleted, but not when the CDC10 septin gene was deleted. AspC also induced atypical pseudohyphae when S. cerevisiae genes encoding Cdc12-interacting proteins Bem4, Cla4, Gic1 and Gic2 were deleted, but not when BNI1, a Cdc12 interacting formin gene, was deleted. AspC localized to bud and pseudohypha necks, while its S. cerevisiae ortholog, Cdc12, localized only to bud necks. CONCLUSIONS/SIGNIFICANCE: Our results suggest that AspC competes with Cdc12 for incorporation into the yeast septin scaffold and once there alters cell shape by altering interactions with the formin Bni1. That introduction of the A. nidulans septin AspC into S. cerevisiae induces a shift from formation of buds to formation of atypical pseudohyphae suggests that septins play an important role in the morphological plasticity of fungi. PMID- 20360847 TI - Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies. AB - BACKGROUND: Effective vaccines to combat malaria are urgently needed, but have proved elusive in the absence of validated correlates of natural immunity. Repeated blood stage infections induce antibodies considered to be the main arbiters of protection from pathology, but their essential functions have remained speculative. METHODOLOGY/PRINCIPAL FINDINGS: This study evaluated antibody dependent respiratory burst (ADRB) activity in polymorphonuclear neutrophils (PMN) induced by Plasmodium falciparum merozoites and antibodies in the sera of two different African endemic populations, and investigated its association with naturally acquired clinical protection. Respiratory bursts by freshly isolated PMN were quantified by chemiluminescence readout in the presence of isoluminol, which preferentially detects extra-cellular reactive oxygen species (ROS). Using a standardized, high throughput protocol, 230 sera were analyzed from individuals of all age groups living in meso- (Ndiop) or holo endemic (Dielmo) Senegalese villages, and enrolled in a cross-sectional prospective study with intensive follow-up. Statistical significance was determined using non-parametric tests and Poisson regression models. The most important finding was that PMN ADRB activity was correlated with acquired clinical protection from malaria in both high and low transmission areas (P = 0.006 and 0.036 respectively). Strikingly, individuals in Dielmo with dichotomized high ADRB indexes were seventeen fold less susceptible to malaria attacks (P = 0.006). Complementary results showed that ADRB activity was (i) dependent on intact merozoites and IgG opsonins, but not parasitized erythrocytes, or complement, (ii) correlated with merozoite specific cytophilic IgG1 and IgG3 antibody titers (P<0.001 for both), and (iii) stronger in antisera from a holo-endemic compared to a meso-endemic site (P = 0.002), and reduced in asymptomatic carriers (P<0.001). CONCLUSIONS/SIGNIFICANCE: This work presents the first clearly demonstrated functional antibody immune correlate of clinical protection from Plasmodium falciparum malaria, and begs the question regarding the importance of ADRB by PMN for immune protection against malaria in vivo. PMID- 20360846 TI - Tgf-Beta inhibition restores terminal osteoblast differentiation to suppress myeloma growth. AB - BACKGROUND: Multiple myeloma (MM) expands almost exclusively in the bone marrow and generates devastating bone lesions, in which bone formation is impaired and osteoclastic bone resorption is enhanced. TGF-beta, a potent inhibitor of terminal osteoblast (OB) differentiation, is abundantly deposited in the bone matrix, and released and activated by the enhanced bone resorption in MM. The present study was therefore undertaken to clarify the role of TGF-beta and its inhibition in bone formation and tumor growth in MM. METHODOLOGY/PRINCIPAL FINDINGS: TGF-beta suppressed OB differentiation from bone marrow stromal cells and MC3T3-E1 preosteoblastic cells, and also inhibited adipogenesis from C3H10T1/2 immature mesenchymal cells, suggesting differentiation arrest by TGF beta. Inhibitors for a TGF-beta type I receptor kinase, SB431542 and Ki26894, potently enhanced OB differentiation from bone marrow stromal cells as well as MC3T3-E1 cells. The TGF-beta inhibition was able to restore OB differentiation suppressed by MM cell conditioned medium as well as bone marrow plasma from MM patients. Interestingly, TGF-beta inhibition expedited OB differentiation in parallel with suppression of MM cell growth. The anti-MM activity was elaborated exclusively by terminally differentiated OBs, which potentiated the cytotoxic effects of melphalan and dexamethasone on MM cells. Furthermore, TGF-beta inhibition was able to suppress MM cell growth within the bone marrow while preventing bone destruction in MM-bearing animal models. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that TGF-beta inhibition releases stromal cells from their differentiation arrest by MM and facilitates the formation of terminally differentiated OBs, and that terminally differentiated OBs inhibit MM cell growth and survival and enhance the susceptibility of MM cells to anti-MM agents to overcome the drug resistance mediated by stromal cells. Therefore, TGF-beta appears to be an important therapeutic target in MM bone lesions. PMID- 20360848 TI - Total energy expenditure and body composition in two free-living sympatric lemurs. AB - BACKGROUND: Evolutionary theories that account for the unusual socio-ecological traits and life history features of group-living prosimians, compared with other primates, predict behavioral and physiological mechanisms to conserve energy. Low energy output and possible fattening mechanisms are expected, as either an adaptive response to drastic seasonal fluctuations of food supplies in Madagascar, or persisting traits from previously nocturnal hypometabolic ancestors. Free ranging ring-tailed lemurs (Lemur catta) and brown lemurs (Eulemur sp.) of southern Madagascar have different socio-ecological characteristics which allow a test of these theories: Both gregarious primates have a phytophagous diet but different circadian activity rhythms, degree of arboreality, social systems, and slightly different body size. METHODOLOGY AND RESULTS: Daily total energy expenditure and body composition were measured in the field with the doubly labeled water procedure. High body fat content was observed at the end of the rainy season, which supports the notion that individuals need to attain a sufficient physical condition prior to the long dry season. However, ring-tailed lemurs exhibited lower water flux rates and energy expenditure than brown lemurs after controlling for body mass differences. The difference was interpreted to reflect higher efficiency for coping with seasonally low quality foods and water scarcity. Daily energy expenditure of both species was much less than the field metabolic rates predicted by various scaling relationships found across mammals. DISCUSSION: We argue that low energy output in these species is mainly accounted for by low basal metabolic rate and reflects adaptation to harsh, unpredictable environments. The absence of observed sex differences in body weight, fat content, and daily energy expenditure converge with earlier investigations of physical activity levels in ring-tailed lemurs to suggest the absence of a relationship between energy constraints and the evolution of female dominance over males among lemurs. Nevertheless, additional seasonal data are required to provide a definitive conclusion. PMID- 20360849 TI - Discriminating natural image statistics from neuronal population codes. AB - The power law provides an efficient description of amplitude spectra of natural scenes. Psychophysical studies have shown that the forms of the amplitude spectra are clearly related to human visual performance, indicating that the statistical parameters in natural scenes are represented in the nervous system. However, the underlying neuronal computation that accounts for the perception of the natural image statistics has not been thoroughly studied. We propose a theoretical framework for neuronal encoding and decoding of the image statistics, hypothesizing the elicited population activities of spatial-frequency selective neurons observed in the early visual cortex. The model predicts that frequency tuned neurons have asymmetric tuning curves as functions of the amplitude spectra falloffs. To investigate the ability of this neural population to encode the statistical parameters of the input images, we analyze the Fisher information of the stochastic population code, relating it to the psychophysically measured human ability to discriminate natural image statistics. The nature of discrimination thresholds suggested by the computational model is consistent with experimental data from previous studies. Of particular interest, a reported qualitative disparity between performance in fovea and parafovea can be explained based on the distributional difference over preferred frequencies of neurons in the current model. The threshold shows a peak at a small falloff parameter when the neuronal preferred spatial frequencies are narrowly distributed, whereas the threshold peak vanishes for a neural population with a more broadly distributed frequency preference. These results demonstrate that the distributional property of neuronal stimulus preference can play a crucial role in linking microscopic neurophysiological phenomena and macroscopic human behaviors. PMID- 20360850 TI - Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. AB - BACKGROUND: Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)(2)D3, as well as 1-hydroxyvitamin D3 to 1alpha,20 dihydroxyvitamin D3 (1,20(OH)(2)D3). It also cleaves the side chain of 7 dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL). METHODS AND FINDINGS: To define the biological significance of these P450scc-initiated pathways, we tested the effects of their 5,7-diene precursors and secosteroidal products on leukemia cell differentiation and proliferation in comparison to 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D3). These secosteroids inhibited proliferation and induced erythroid differentiation of K562 human chronic myeloid and MEL mouse leukemia cells with 20(OH)D3 and 20,23(OH)(2)D3 being either equipotent or slightly less potent than 1,25(OH)(2)D3, while 1,20(OH)(2)D3, pD and pL compounds were slightly or moderately less potent. The compounds also inhibited proliferation and induced monocytic differentiation of HL-60 promyelocytic and U937 promonocytic human leukemia cells. Among them 1,25(OH)(2)D3 was the most potent, 20(OH)D3, 20,23(OH)(2)D3 and 1,20(OH)(2)D3 were less active, and pD and pL compounds were the least potent. Since it had been previously proven that secosteroids without the side chain (pD) have no effect on systemic calcium levels we performed additional testing in rats and found that 20(OH)D3 had no calcemic activity at concentration as high as 1 microg/kg, whereas, 1,20(OH)(2)D3 was slightly to moderately calcemic and 1,25(OH)(2)D3 had strong calcemic activity. CONCLUSIONS: We identified novel secosteroids that are excellent candidates for anti-leukemia therapy with 20(OH)D3 deserving special attention because of its relatively high potency and lack of calcemic activity. PMID- 20360851 TI - Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice. AB - CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36( /-)) mice. Feeding CD36(-/-) mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/-) mice and cholesterol uptake from HDL or LDL by isolated CD36(-/-) hepatocytes was unaltered. However, CD36(-/-) hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/-) macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/-) cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition. PMID- 20360852 TI - SWISS MADE: Standardized WithIn Class Sum of Squares to evaluate methodologies and dataset elements. AB - Contemporary high dimensional biological assays, such as mRNA expression microarrays, regularly involve multiple data processing steps, such as experimental processing, computational processing, sample selection, or feature selection (i.e. gene selection), prior to deriving any biological conclusions. These steps can dramatically change the interpretation of an experiment. Evaluation of processing steps has received limited attention in the literature. It is not straightforward to evaluate different processing methods and investigators are often unsure of the best method. We present a simple statistical tool, Standardized WithIn class Sum of Squares (SWISS), that allows investigators to compare alternate data processing methods, such as different experimental methods, normalizations, or technologies, on a dataset in terms of how well they cluster a priori biological classes. SWISS uses Euclidean distance to determine which method does a better job of clustering the data elements based on a priori classifications. We apply SWISS to three different gene expression applications. The first application uses four different datasets to compare different experimental methods, normalizations, and gene sets. The second application, using data from the MicroArray Quality Control (MAQC) project, compares different microarray platforms. The third application compares different technologies: a single Agilent two-color microarray versus one lane of RNA-Seq. These applications give an indication of the variety of problems that SWISS can be helpful in solving. The SWISS analysis of one-color versus two-color microarrays provides investigators who use two-color arrays the opportunity to review their results in light of a single-channel analysis, with all of the associated benefits offered by this design. Analysis of the MACQ data shows differential intersite reproducibility by array platform. SWISS also shows that one lane of RNA-Seq clusters data by biological phenotypes as well as a single Agilent two-color microarray. PMID- 20360853 TI - Cooperative interactions between TLR4 and TLR9 regulate interleukin 23 and 17 production in a murine model of gram negative bacterial pneumonia. AB - Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4(lps-d)), mice deficient in TLR9 (TLR9(-/ )) and TLR4/9 double mutant mice (TLR4(lps-d)/TLR9(-/-)) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4(lps-d)/TLR9(-/-) double mutant mice. Early lung expression of TNF-alpha, IL-12, and chemokines was TLR4 dependent, while IFN-gamma production and the later expression of TNF-alpha and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4(lps-d)/TLR9(-/-) double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response. PMID- 20360854 TI - DNA-mediated self-assembly of artificial vesicles. AB - BACKGROUND: Although multicompartment systems made of single unilamellar vesicles offer the potential to outperform single compartment systems widely used in analytic, synthetic, and medical applications, their use has remained marginal to date. On the one hand, this can be attributed to the binary character of the majority of the current tethering protocols that impedes the implementation of real multicomponent or multifunctional systems. On the other hand, the few tethering protocols theoretically providing multicompartment systems composed of several distinct vesicle populations suffer from the readjustment of the vesicle formation procedure as well as from the loss of specificity of the linking mechanism over time. METHODOLOGY/PRINCIPAL FINDINGS: In previous studies, we presented implementations of multicompartment systems and resolved the readjustment of the vesicle formation procedure as well as the loss of specificity by using linkers consisting of biotinylated DNA single strands that were anchored to phospholipid-grafted biotinylated PEG tethers via streptavidin as a connector. The systematic analysis presented herein provides evidences for the incorporation of phospholipid-grafted biotinylated PEG tethers to the vesicle membrane during vesicle formation, providing specific anchoring sites for the streptavidin loading of the vesicle membrane. Furthermore, DNA-mediated vesicle vesicle self-assembly was found to be sequence-dependent and to depend on the presence of monovalent salts. CONCLUSIONS/SIGNIFICANCE: This study provides a solid basis for the implementation of multi-vesicle assemblies that may affect at least three distinct domains. (i) Analysis. Starting with a minimal system, the complexity of a bottom-up system is increased gradually facilitating the understanding of the components and their interaction. (ii) Synthesis. Consecutive reactions may be implemented in networks of vesicles that outperform current single compartment bioreactors in versatility and productivity. (iii) Personalized medicine. Transport and targeting of long-lived, pharmacologically inert prodrugs and their conversion to short-lived, active drug molecules directly at the site of action may be accomplished if multi-vesicle assemblies of predefined architecture are used. PMID- 20360855 TI - An expanded self-antigen peptidome is carried by the human lymph as compared to the plasma. AB - BACKGROUND: The pre-nodal afferent lymph is the fluid which directly derives from the extracellular milieu from every parenchymal organ and, as it continues to circulate between the cells, it collects products deriving from the organ metabolism/catabolism. A comprehensive qualitative and quantitative investigation of the self-antigenic repertoire transported by the human lymph is still missing. METHODOLOGY/PRINCIPAL FINDINGS: A major difference between lymph and plasma could be visualized by FPLC and 2D gel in the amount of low molecular weight products corresponding to peptide fragments. Naturally processed peptides in normal pre nodal human lymph were then fractionated by HPLC and characterized by multidimensional mass spectrometry. Analysis of more then 300 sequences identified self-peptides derived from both intracellular and extracellular proteins revealing the variety of catabolic products transported by human lymph. Quantitative analysis established that at least some of these peptides are present in the circulating lymph in nanomolar concentration. CONCLUSIONS/SIGNIFICANCE: The peptidome, generated by physiological tissue catabolism and transported by the pre-nodal lymph, is in addition to the self peptidome generated in endosomal compartment. Unlike self antigen processed by local or nodal APC, which mostly produce epitopes constrained by the endosomal processing activity, self antigens present in the lymph could derived from a wider variety of processing pathways; including caspases, involved in cellular apoptosis, and ADAM and other metalloproteinases involved in surface receptor editing, cytokines processing and matrix remodeling. Altogether, expanding the tissue-specific self-repertoire available for the maintenance of immunological tolerance. PMID- 20360856 TI - Oligomeric interfaces under the lens: gemini. AB - The assembly of subunits in protein oligomers is an important topic to study as a vast number of proteins exists as stable or transient oligomer and because it is a mechanism used by some protein oligomers for killing cells (e.g., perforin from the human immune system, pore-forming toxins from bacteria, phage, amoeba, protein misfolding diseases, etc.). Only a few of the amino acids that constitute a protein oligomer seem to regulate the capacity of the protein to assemble (to form interfaces), and some of these amino acids are localized at the interfaces that link the different chains. The identification of the residues of these interfaces is rather difficult. We have developed a series of programs, under the common name of Gemini, that can select the subset of the residues that is involved in the interfaces of a protein oligomer of known atomic structure, and generate a 2D interaction network (or graph) of the subset. The graphs generated for several oligomers demonstrate the accuracy of the selection of subsets that are involved in the geometrical and the chemical properties of interfaces. The results of the Gemini programs are in good agreement with those of similar programs with an advantage that Gemini programs can perform the residue selection much more rapidly. Moreover, Gemini programs can also perform on a single protein oligomer without the need of comparison partners. The graphs are extremely useful for comparative studies that would help in addressing questions not only on the sequence specificity of protein interfaces but also on the mechanism of the assembly of unrelated protein oligomers. PMID- 20360857 TI - Specific functions of BIG1 and BIG2 in endomembrane organization. AB - BACKGROUND: Transport of molecules from one subcellular compartment to another involves the recruitment of cytosolic coat protein complexes to a donor membrane to concentrate cargo, deform the membrane and ultimately to form an independent carrier. Small-GTP-binding proteins of the Arf family are central to many membrane trafficking events. Arfs are activated by guanine nucleotide exchange factors (GEFs) which results in their recruitment to membranes and subsequent engagement with Arf-effectors, many of which are coat proteins. Among the human BFA-sensitive large Arf-GEFs, the function of the two closely related BIG1 and BIG2 is still not clear, and recent studies have raised the question of functional redundancy between the two proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used small-interfering RNA on human cells and a combination of fixed and live-cell imaging to investigate the differential functions of BIG1 and BIG2 in endomembrane organization and function. Importantly, in this direct comparative study, we show discrete functions for BIG1 and BIG2. Our results show that depletion of BIG2 but not of BIG1 induces a tubulation of the recycling endosomal compartment, consistent with a specific role for BIG2 here. In contrast, suppression of BIG1 induces the formation of Golgi mini-stacks still polarized and functional in terms of cargo export. CONCLUSIONS: A key finding from our work is that suppression of BIG1 expression results in a fragmentation of the Golgi apparatus. Our data indicate that the human BFA-sensitive large Arf GEFs have non-redundant functions in cell organization and membrane trafficking. BIG1 is required to maintain the normal morphology of the Golgi; BIG2 is important for endosomal compartment integrity and cannot replace the function of BIG1 in Golgi organization. PMID- 20360858 TI - Actin re-organization induced by Chlamydia trachomatis serovar D--evidence for a critical role of the effector protein CT166 targeting Rac. AB - The intracellular bacterium Chlamydia trachomatis causes infections of urogenital tract, eyes or lungs. Alignment reveals homology of CT166, a putative effector protein of urogenital C. trachomatis serovars, with the N-terminal glucosyltransferase domain of clostridial glucosylating toxins (CGTs). CGTs contain an essential DXD-motif and mono-glucosylate GTP-binding proteins of the Rho/Ras families, the master regulators of the actin cytoskeleton. CT166 is preformed in elementary bodies of C. trachomatis D and is detected in the host cell shortly after infection. Infection with high MOI of C. trachomatis serovar D containing the CT166 ORF induces actin re-organization resulting in cell rounding and a decreased cell diameter. A comparable phenotype was observed in HeLa cells treated with the Rho-GTPase-glucosylating Toxin B from Clostridium difficile (TcdB) or HeLa cells ectopically expressing CT166. CT166 with a mutated DXD-motif (CT166-mut) exhibited almost unchanged actin dynamics, suggesting that CT166 induced actin re-organization depends on the glucosyltransferase motif of CT166. The cytotoxic necrotizing factor 1 (CNF1) from E. coli deamidates and thereby activates Rho-GTPases and transiently protects them against TcdB-induced glucosylation. CNF1-treated cells were found to be protected from TcdB- and CT166 induced actin re-organization. CNF1 treatment as well as ectopic expression of non-glucosylable Rac1-G12V, but not RhoA-G14A, reverted CT166-induced actin re organization, suggesting that CT166-induced actin re-organization depends on the glucosylation of Rac1. In accordance, over-expression of CT166-mut diminished TcdB induced cell rounding, suggesting shared substrates. Cell rounding induced by high MOI infection with C. trachomatis D was reduced in cells expressing CT166 mut or Rac1-G12V, and in CNF1 treated cells. These observations indicate that the cytopathic effect of C. trachomatis D is mediated by CT166 induced Rac1 glucosylation. Finally, chlamydial uptake was impaired in CT166 over-expressing cells. Our data strongly suggest CT166's participation as an effector protein during host-cell entry, ensuring a balanced uptake into host-cells by interfering with Rac-dependent cytoskeletal changes. PMID- 20360859 TI - Contribution of company affiliation and social contacts to risk estimates of between-farm transmission of avian influenza. AB - BACKGROUND: Models of between-farm transmission of pathogens have identified service vehicles and social groups as risk factors mediating the spread of infection. Because of high levels of economic organization in much of the poultry industry, we examined the importance of company affiliation, as distinct from social contacts, in a model of the potential spread of avian influenza among broiler poultry farms in a poultry-dense region in the United States. The contribution of company affiliation to risk of between-farm disease transmission has not been previously studied. METHODOLOGY/PRINCIPAL FINDINGS: We obtained data on the nature and frequency of business and social contacts through a national survey of broiler poultry growers in the United States. Daily rates of contact were estimated using Monte Carlo analysis. Stochastic modeling techniques were used to estimate the exposure risk posed by a single infectious farm to other farms in the region and relative risk of exposure for farms under different scenarios. The mean daily rate of vehicular contact was 0.82 vehicles/day. The magnitude of exposure risk ranged from <1% to 25% under varying parameters. Risk of between-farm transmission was largely driven by company affiliation, with farms in the same company group as the index farm facing as much as a 5-fold increase in risk compared to farms contracted with different companies. Employment of part-time workers contributed to significant increases in risk in most scenarios, notably for farms who hired day-laborers. Social visits were significantly less important in determining risk. CONCLUSIONS/SIGNIFICANCE: Biosecurity interventions should be based on information on industry structure and company affiliation, and include part-time workers as potentially unrecognized sources of viral transmission. Modeling efforts to understand pathogen transmission in the context of industrial food animal production should consider company affiliation in addition to geospatial factors and pathogen characteristics. Restriction of social contacts among farmers may be less useful in reducing between-farm transmission. PMID- 20360860 TI - Arabidopsis thaliana GYRB3 does not encode a DNA gyrase subunit. AB - BACKGROUND: DNA topoisomerases are enzymes that control the topology of DNA in all cells. DNA gyrase is unique among the topoisomerases in that it is the only enzyme that can actively supercoil DNA using the free energy of ATP hydrolysis. Until recently gyrase was thought to be unique to bacteria, but has now been discovered in plants. The genome of the model plant, Arabidopsis thaliana, is predicted to encode four gyrase subunits: AtGyrA, AtGyrB1, AtGyrB2 and AtGyrB3. METHODOLOGY/PRINCIPAL FINDINGS: We found, contrary to previous data, that AtGyrB3 is not essential to the survival of A. thaliana. Bioinformatic analysis suggests AtGyrB3 is considerably shorter than other gyrase B subunits, lacking part of the ATPase domain and other key motifs found in all type II topoisomerases; but it does contain a putative DNA-binding domain. Partially purified AtGyrB3 cannot bind E. coli GyrA or support supercoiling. AtGyrB3 cannot complement an E. coli gyrB temperature-sensitive strain, whereas AtGyrB2 can. Yeast two-hybrid analysis suggests that AtGyrB3 cannot bind to AtGyrA or form a dimer. CONCLUSIONS/SIGNIFICANCE: These data strongly suggest that AtGyrB3 is not a gyrase subunit but has another unknown function. One possibility is that it is a nuclear protein with a role in meiosis in pollen. PMID- 20360861 TI - A systems biology approach to transcription factor binding site prediction. AB - BACKGROUND: The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs), identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates. METHODOLOGY/PRINCIPAL FINDINGS: We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs) and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data. CONCLUSIONS/SIGNIFICANCE: Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct interaction detection and TFBS-discovery accuracy. We estimated the accuracy of our framework on a human B-cell specific test set, which may help guide future methodological development. PMID- 20360862 TI - Mycoplasma suppression of THP-1 Cell TLR responses is corrected with antibiotics. AB - Mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. We found that chronic mycoplasma contamination of THP-1 cells suppresses responses of THP-1 cells to TLR stimuli. For example, E. coli LPS induced IL-1 beta was suppressed by 6 fold and IL-8 by 10 fold in mycoplasma positive THP-1 cells. Responses to live F. novicida challenge were suppressed by 50-fold and 40 fold respectively for IL-1beta and IL-8. Basal TLR4 expression level in THP-1 cells was decreased by mycoplasma by 2.4-fold (p = 0.0003). Importantly, cell responses to pathogen associated molecular patterns are completely restored by mycoplasma clearance with Plasmocin. Thus, routine screening of cell lines for mycoplasma is important for the maintenance of reliable experimental data and contaminated cell lines can be restored to their baseline function with antibiotic clearance of mycoplasma. PMID- 20360863 TI - Evidence for large complex networks of plant short silencing RNAs. AB - BACKGROUND: In plants and animals there are many classes of short RNAs that carry out a wide range of functions within the cell; short silencing RNAs (ssRNAs) of 21-25 nucleotides in length are produced from double-stranded RNA precursors by the protein Dicer and guide nucleases and other proteins to their RNA targets through base pairing interactions. The consequence of this process is degradation of the targeted RNA, suppression of its translation or initiation of secondary ssRNA production. The secondary ssRNAs in turn could then initiate further layers of ssRNA production to form extensive cascades and networks of interacting RNA [1]. Previous empirical analysis in plants established the existence of small secondary ssRNA cascade [2], in which a single instance of this event occurred but it was not known whether there are other more extensive networks of secondary sRNA production. METHODOLOGY/PRINCIPAL FINDINGS: We generated a network by predicting targets of ssRNA populations obtained from high-throughput sequencing experiments. The topology of the network shows it to have power law connectivity distribution, to be dissortative, highly clustered and composed of multiple components. We also identify protein families, PPR and ULP1, that act as hubs within the network. Comparison of the repetition of genomic sub-sequences of ssRNA length between Arabidopsis and E.coli suggest that the network structure is made possible by the underlying repetitiveness in the genome sequence. CONCLUSIONS/SIGNIFICANCE: Together our results provide good evidence for the existence of a large, robust ssRNA interaction network with distinct regulatory function. Such a network could have a massive effect on the regulation of gene expression via mediation of transcript levels. PMID- 20360864 TI - Allele-specific regulation of matrix metalloproteinase-3 gene by transcription factor NFkappaB. AB - BACKGROUND: Matrix metalloproteinase-3 (MMP3) is implicated in the pathogenesis and progression of atherosclerotic lesions. Previous studies suggested that MMP3 expression is influenced by a polymorphism (known as the 5A/6A polymorphism) in the promoter of the MMP3 gene and that this polymorphism is located within a cis element that interacts with the transcription factor NFkappaB. In the present study, we sought to investigate whether MMP3 and NFkappaB were co-localized in atherosclerotic lesions and whether NFkappaB had differential effects on the two alleles of the MMP3 5A/6A polymorphism. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical examination showed that MMP3 and both the NFkappaB p50 and p65 subunits were expressed abundantly in macrophages in atherosclerotic lesions and that MMP3 expression was co-localized with p50 and p65. Chromatin immunoprecipitation experiments showed interaction of p50 and p65 with the MMP3 promoter in macrophages, with greater binding to the 5A allele than to the 6A allele. Reporter gene assays in transiently transfected macrophages showed that the 5A allele had greater transcriptional activity than the 6A allele, and that this allele-specific effect was augmented when the cells were treated with the NFkappaB activator lipopolysaccharides or co-transfected with p50 and/or p65 expressing plasmids, but was reduced when the cells were treated with the NFkappaB inhibitor 6-Amino-4-(4-phenoxyphenylethylamino)-quinazoline or transfected with a dominant negative mutant of IkB kinase-beta. CONCLUSION: These results corroborate an effect of the 5A/6A polymorphism on MMP3 transcription and indicate that NFkappaB has differential effects on the 5A and 6A alleles. PMID- 20360867 TI - Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients' skin which are normalized by kidney-pancreas transplantation. AB - BACKGROUND: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. METHODS AND FINDINGS: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase delta chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. CONCLUSIONS: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs. PMID- 20360868 TI - Estimating the disease burden of pandemic (H1N1) 2009 virus infection in Hunter New England, Northern New South Wales, Australia, 2009. AB - INTRODUCTION: On May 26, 2009, the first confirmed case of Pandemic (H1N1) 2009 virus (pH1N1) infection in Hunter New England (HNE), New South Wales (NSW), Australia (population 866,000) was identified. We used local surveillance data to estimate pH1N1-associated disease burden during the first wave of pH1N1 circulation in HNE. METHODS: Surveillance was established during June 1-August 30, 2009, for: 1) laboratory detection of pH1N1 at HNE and NSW laboratories, 2) pH1N1 community influenza-like illness (ILI) using an internet survey of HNE residents, and 3) pH1N1-associated hospitalizations and deaths using respiratory illness International Classification of Diseases 10 codes at 35 HNE hospitals and mandatory reporting of confirmed pH1N1-associated hospitalizations and deaths to the public health service. The proportion of pH1N1 positive specimens was applied to estimates of ILI, hospitalizations, and deaths to estimate disease burden. RESULTS: Of 34,177 specimens tested at NSW laboratories, 4,094 (12%) were pH1N1 positive. Of 1,881 specimens from patients evaluated in emergency departments and/or hospitalized, 524 (26%) were pH1N1 positive. The estimated number of persons with pH1N1-associated ILI in the HNE region was 53,383 (range 37,828 70,597) suggesting a 6.2% attack rate (range 4.4-8.2%). An estimated 509 pH1N1 associated hospitalizations (range 388-630) occurred (reported: 184), and up to 10 pH1N1-associated deaths (range 8-13) occurred (reported: 5). The estimated case hospitalization ratio was 1% and case fatality ratio was 0.02%. DISCUSSION: The first wave of pH1N1 activity in HNE resulted in symptomatic infection in a small proportion of the population, and the number of HNE pH1N1-associated hospitalizations and deaths is likely higher than officially reported. PMID- 20360869 TI - Optimization of piezoelectric properties for [001](c) poled 0.94Pb(Zn(13)Nb(23))O(3)-0.06PbTiO(3) single crystals. AB - The piezoelectric properties of [001](c) poled 0.94Pb(Zn(13)Nb(23))O(3) 0.06PbTiO(3) single crystals were greatly enhanced by controlling their domain configurations. Contrary to the interpretation of charged domain walls being the main contributor to the piezoelectric enhancement, we found that smaller domain size and more neutral domain walls were the main contributors for the piezoelectric enhancement of these multidomain crystals. The properties of 109 degrees neutral domain walls in 0.94Pb(Zn(13)Nb(23))O(3)-0.06PbTiO(3) single crystals were extracted by using a piezoelectric domain wall model. PMID- 20360870 TI - Effects of metallic silver particles on the emission properties of [Ru(bpy)(3)]. AB - We examined the emission spectral properties of [Ru(bpy)(3)](2+) in a thin film of polyvinyl alcohol coated on quartz slides or on metallic silver particles. The relative intensities were several fold higher on the surface containing silver particles, and the decay times were several fold smaller. These results are consistent with an approximate 20-fold increase in the radiative decay rate of [Ru(bpy)(3)](2+) when near metallic silver particles. These results suggest the use of silver particles for increased detectability of the emission from transition metal-ligand complexes. PMID- 20360871 TI - The efficacy of Artecoll injections for the augmentation of nipple projection in breast reconstruction. AB - INTRODUCTION: Various techniques have been used in an attempt to achieve long term nipple projection following nipple-areolar reconstruction. A common setback, however, is the diminution of projection overtime; this phenomenon is particularly evident following implant-based breast reconstruction. Artecoll may be suitable for injection into the nipple complex to maintain permanent, 3 dimensional projection. Artecoll is an injectable substance that is biocompatible and immunologically inert and resists degradation in vivo. The purpose of this study was thus to prospectively evaluate the efficacy of Artecoll (polymethylmethacrylate microspheres suspended in 3.5% denatured bovine collagen with 0.3% lidocaine) in obtaining and maintaining nipple projection following postmastectomy, nipple-areolar reconstruction. METHODS: A prospective, clinical trial was performed. Consecutive patients deemed to have inadequate nipple projection at least 6 months following "C-V flap" or "modified-skate flap" reconstruction were identified. Only women who had postmastectomy reconstruction with tissue expanders and implants were considered eligible for participation. Artecoll was injected under the nipple at 2 time points: baseline and 3 months. Calipers were used to measure nipple projection preinjection and postinjection at baseline, 3, 6, and 9 months. RESULTS: Thirty-three nipples were injected in 23 patients. There were no adverse events. Prior to injection, mean nipple projection was 1.33 +/- 1.0 mm. The mean increase in projection over the 9-month study period was both clinically and statistically significant (1.60 +/- 1.24 mm; P <.001). A history of prior irradiation was a significant negative predictor of final nipple projection (P = .012). CONCLUSION: Artecoll injection is both feasible and effective in increasing and maintaining nipple projection in the setting of implant-based breast reconstruction. PMID- 20360872 TI - The effect of W-plasty on cheek rotation flap. PMID- 20360873 TI - Collateral ligament injuries of the metacarpophalangeal joint of the thumb: a treatment algorithm. AB - The management of injury to the ulnar and radial collateral ligaments at the metacarpophalangeal joint of the thumb is complex. Treatment is dependent upon a number of factors with a wide variety of options for each ligament. Inadequate treatment has the potential to lead to a poor functional outcome. We present the relevant clinical anatomy, mechanism of injury, methods of treatment available and suggest a single treatment algorithm for use in the management of these injuries. PMID- 20360874 TI - Bone transport using the Ilizarov method: a review of complications in 100 consecutive cases. AB - We present the results of treatment of 100 patients (72 men, 28 women) by the Ilizarov method of bone transport using circular (55) and monolateral external fixators (45). A total of 26 femurs (18 monolateral, 8 circular) and 74 tibias (49 circular, 25 monolateral) was examined. There were no significant differences between the circular fixator and the monolateral fixator with regard to treatment time, complications in the treated bone segments or compliance with the presence of the fixator. The main complications (pseudoarthrosis at bone contact points after transport, insufficient ossification of lengthened bone, knee stiffness) were resolved with further treatment for all patients with the exception of one case which continued with repeated infections. The circular fixator allows for deformity corrections during bone transport but the monolateral fixator is tolerated better by patients, especially in those with femoral defects. PMID- 20360875 TI - Direct exchange endoprosthetic reconstruction with tumour prosthesis for periprosthetic knee infection associated with segmental bone defects. AB - Revision knee arthroplasty for infection poses a treatment challenge. The presence of massive osteolysis limits the treatment options in this cohort. Controversy exists in the management of these patients. Direct exchange arthroplasty has provided good results in the presence of infection, but whether this is appropriate in the presence of massive bone defects associated with the infection is undetermined. We present our experience in revision knee arthroplasty for infection associated with massive bone defects. The aim of the study is to present the preliminary results of a direct exchange endoprosthetic reconstruction with tumour prosthesis for periprosthetic infection associated with segmental bone defects. This is a retrospective study of prospectively collected data, involving six patients with periprosthetic infection and massive bone defects treated by direct exchange tumour prostheses between 2003 and 2007 (four distal femoral replacements and two total femoral replacements). The mean age and follow-up were 74.2 (+/-5.2) years and 32.5 (+/-8.2) months respectively. Each patient had an infected revised knee arthroplasty at the time of referral to our institution. Staphylococcus aureus was the most common causal organism. The mean duration of antibiotics was 6 weeks intravenous therapy followed by 3.5 months oral. The recurrences of infection, pain or immobility were outcome criteria considered failures. Our success rate was 80%. Salvage of infected revised knee arthroplasty by direct exchange endoprosthetic reconstruction has provided an effective means of pain relief, joint stability and improved mobility in our cohort. It reduces morbidity through earlier mobilisation and avoids a second major operation. PMID- 20360876 TI - Minimally invasive, no hardware subtalar arthrodesis with autogenous posterior iliac bone graft. AB - Sixteen patients underwent minimally invasive subtalar arthrodesis through a mini invasive approach with posterior iliac graft between 2004 and 2006. No hardware was used to transfix the arthrodesis and partial weight bearing was allowed immediately. The primary indication for surgery was the squeal of fracture os calcis in terms of subtalar joint arthritis, loss of heel height, malalignment of the hindfoot, and pain with weight bearing. There were 12 male and 4 female patients with a mean age of 30 (range 17-52). Patients were followed up for a period of 40.8 months (range 36-48 months). The mean interval from injury to fusion was 2 (+0.6) years ranging from 6 months to 6 years post fracture. The average clinical rating scale based on the American Orthopaedic Foot and Ankle Society (AOFAS) improved from 36 preoperatively to 78 at the latest follow-up (P < 0.05). Union rate was 94%. Radiographic evaluation revealed a mean increase in calcaneal inclination of 6.25 + 8.3 degrees (P < 0.07) and a mean increase in the lateral talocalcaneal angle of 7.42 + 10.2 degrees (P < 0.08). Complications were graft nonunion in 1 patient and transient tendoachilles tendinitis in another. This technique can be used to decrease the morbidity associated with the late complications of os calcis fractures by aligning the hindfoot, restoring the heel height and correcting calcaneal and talar inclination. It offers the advantage of early weight bearing while avoiding hardware complications. PMID- 20360877 TI - A polytrauma patient with an unusual posterior fracture-dislocation of the femoral head: a case report. AB - We report a case of a 27-year-old man who was involved in a high-speed car accident. He sustained multiple organ damage including multiple brain petechiae suggesting diffuse axonal damage, aortic dissection, retroperitoneal haematoma and a fracture-dislocation of the right hip with a femoral head fracture and an ipsilateral intertrochanteric fracture. Due to the general condition of the patient, physiological stabilisation was prioritized, and at 2 weeks the fracture dislocation of the hip was treated with a proximal femoral nail for the intertrochanteric fracture and Herbert screws for the femoral head fracture. Postoperatively, two episodes of recurrent hip dislocation occurred, and this was stabilized eventually with a Steinman pin inserted across the hip joint and taken out 1 month later. Weight-bearing was allowed according to clinical and radiographical assessments. Heterotopic ossification developed around the hip joint, but without evidence of AVN or osteoarthritis. At 18-months follow-up, the fractures had healed and the patient had a Harris Hip score of 79.1. Anatomical reduction and stable fixation of fracture-dislocations of the hip are important for achieving an acceptable result. PMID- 20360878 TI - Tuberculous dactylitis pseudotumor of an adult thumb: a case report. AB - Tuberculous dactylitis is an uncommon condition which is particularly difficult to differentiate from other lesions, particularly tumors. We report the case of a 56-year-old, healthy, left-handed person who consulted for progressive painful swelling of 8-month duration in the right thumb, which had developed after direct trauma. The plain radiograph of the thumb revealed extensive destruction of the proximal phalanx associated with pathological fracture. Magnetic resonance imaging (MRI) showed replacement of the affected phalanx with prominent soft tissue mass with extension outside the bone margins. The diagnosis of tuberculous dactylitis was based on histological characteristics and positive acid fast bacilli using Ziehl-Neelsen stain. Surgical debridement and anti-tuberculous chemotherapy eradicated the infection. Seven years post treatment, the patient had good function of the thumb with no significant disability interfering with his daily activity. PMID- 20360879 TI - Tumor lysis syndrome associated with chemotherapy in primary retroperitoneal soft tissue sarcoma by ex vivo ATP-based tumor chemo-sensitivity assay (ATP-TCA). AB - Tumor lysis syndrome (TLS), a result of rapid cell lysis following tumor therapy, is a well recognized complication during the treatment of rapidly growing tumors. TLS rarely occurs in solid tumors. We present a case report of TLS in a patient with primary retroperitoneal soft tissue sarcoma. TLS occurred in the patient after four days' combinational chemotherapy with cisplatin, adriamycin, and dacarbazine. These drugs were selected on the basis of an ex vivo ATP-based tumor sensitivity assay. TLS was properly controlled in the patient with concomitant remission of the sarcoma. Therefore, precautions should be taken to avoid this potentially fatal complication during treatment of solid tumors, especially with tumors highly sensitive to drugs. PMID- 20360880 TI - Progressive multifocal leukoencephalopathy developing in a fludarabine naive patient with chronic lymphocytic leukemia. AB - We report a case of progressive multifocal leukoencephalopathy developing in a fludarabine-naive patient with chronic lymphocytic leukemia. We suggest that progressive multifocal leukoencephalopathy should be considered in any chronic lymphocytic leukemia patient with unexplained neurological symptoms. Treatment history does not necessarily require fludarabine. Intrathecal cytosine arabinoside although unsuccessful in this patient, is a therapeutic option to consider in patients experiencing side effects from systemic therapy. PMID- 20360881 TI - Tumor necrosis factor alpha as a marker of systemic and local inflammation in "healthy" smokers. AB - BACKGROUND: Tobacco smoking induces a local and systemic inflammatory reaction and also a decline in pulmonary function. There are some novel noninvasive methods to measure the degree of inflammatory bronchial reaction, including the exhaled breath condensate (EBC) in which several inflammatory markers can be measured, including tumor necrosis factor alpha (TNF-alpha). There is a clear clinical need to develop methods that allow early detection of smokers at risk of losing pulmonary function. OBJECTIVES: THE AIMS OF THE PRESENT STUDY ARE: 1) to show that smokers show higher levels of TNF-alpha both in serum and EBC; 2) to analyze the possible influence of gender, age, and weight on this parameter; and 3) to determine a possible association between smoking and pulmonary function parameters and TNF-alpha levels. MATERIAL AND METHODS: We have prospectively analyzed two cohorts of smokers and non-smokers subjects without any chronic or acute disease (within eight weeks of study initiation). We have performed pulmonary function tests with bronchodilators and also collected EBC and blood samples before smoking cessation. Statistical analysis was performed with SPSS 11.0 for Windows Statistical Package. RESULTS: The study has enrolled 17 patients (8 smokers), 50% of whom were females. Mean age was 38.59 years old (standard deviation, 7.4). The mean number of cigarettes smoked in the smoker group was 26.14 (11.29) cigarettes/day and the mean age when tobacco first began was 15.14 (2.04) years. We have not been able to show any significant differences in TNF alpha levels according to age or weight. For the whole series we have not found any significant influence of gender in TNF-alpha levels, but after dividing the series in smokers and nonsmokers, we have shown higher levels of TNF-alpha in serum (5.59 [0.26] pg/mL vs 5.56 [0.37] pg/mL; nonsignificant [NS]) and EBC (4.94 [0.41] pg/mL vs 4.22 [0.36] pg/mL; p = 0.031) in male smokers. On the other hand, nonsmoking females showed slightly higher TNF-alpha levels in serum (5.70 [0.50] pg/mL vs 5.42 [0.29] pg/mL; NS) and EBC (4.54 [0.92] vs 4.11 [0.41 pg/mL]; NS). Smokers had higher TNF-alpha levels in EBC (4.46 [0.58] pg/mL vs 4.34 [0.62] pg/mL; NS), while serum TNF-alpha levels were slightly higher in nonsmokers (5.52 [0.56] pg/mL vs 5.50 [0.27] pg/mL; NS). We have not demonstrated any association between tobacco consumption and TNF-alpha levels. We have not shown any significant relation between pulmonary function and the studied parameters, with only a modest association between forced expiratory volume at one second and forced vital capacity and TNF-alpha levels in EBC. CONCLUSION: Smokers show higher TNF-alpha levels in EBC. Among smokers, males show higher levels of TNF in serum and EBC. We have not confirmed any significant influence of age or weight on TNF-alpha levels. These levels do not seem to be influenced either by the amount of tobacco or the time since habit began. We have shown a modest relation between pulmonary function and TNF-alpha levels in EBC. PMID- 20360882 TI - Possible disease remission in patient with invasive bladder cancer with D fraction regimen. AB - Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received an unconventional oral regimen of D-fraction, the bioactive extract of Maitake mushroom (Grifola frondosa), following endoscopic transurethral resection of bladder tumor. Despite a high risk for disease recurrence, follow-up yet indicated no clinical evidence of progression of residual disease or recurrence of invasive cancer. It has been nearly two years but the patient remains remarkably well and appears to be in remission. To our knowledge, this is the first and only case report of possible disease remission in a bladder cancer patient after the two-year follow-up of D-fraction regimen, so that further studies with long terms are required for drawing a relevant conclusion. Nevertheless, it is conceivable that D-fraction is a natural agent that may have clinical implications in patients with superficial bladder tumors. PMID- 20360884 TI - Interaction of Gram-negative bacteria with cationic proteins: Dependence on the surface characteristics of the bacterial cell. AB - Gram-negative bacteria can enter the bloodstream and interact with serum cationic proteins. The character of interaction will depend on the surface characteristics of bacterial cells, which are determined by bacterial chemotype and density of lipopolysaccharide (LPS) packing in the cell wall. It was shown that the lysozyme treatment resulted in the increase sensitivity to hypotonic shock. Significant differences to this effect were found between Escherichia coli strain D21 and D21f2 under treatment with physiological protein concentration. On the basis of electrokinetic measurements and studies of the interaction of cells with lysozyme, the hypothesis was formed that the cell wall of the E. coli strain D21f2 contains more LPS and has a higher density of their packing than the cell wall of the E. coli D21 cells. The effect of lysozyme and lactoferrin on the viability of E. coli cells of two different strains was examined. Lysozyme was found to more effectively inhibit the growth of the E. coli D21 bacteria, and lactoferrin suppressed mainly the growth of the E. coli D21f2 bacteria. These results indicate that the differences in LPS core structure of bacterial R chemotype, which determines surface charge and density of LPS packing, plays an essential role in the mechanisms of interaction of the cationic proteins with the cell wall. PMID- 20360883 TI - Modern approaches to understanding stress and disease susceptibility: A review with special emphasis on respiratory disease. AB - Studies in animals and humans link both physical and psychological stress with an increased incidence and severity of respiratory infections. For this manuscript we define stress as the physiological responses an individual undergoes while adjusting to a continually changing environment. It is known that stressors of various types (psychological/physical) can alter the physiological levels of certain hormones, chemokines and cytokines. These alterations send information to the central nervous system to take necessary action which then sends messages to appropriate organs/tissues/cells to respond. These messages can either activate or suppress the immune system as needed and failure to compensate for this by the body can lead to serious health-related problems. Little is known how stress affects disease susceptibility, yet understanding this mechanism is important for developing effective treatments, and for improving health and food quality. The current review focuses on (a) the effects of psychological stressors in humans and animals, (b) various methodologies employed to understand stress responses and their outcomes, and (c) the current status of the attempts to correlate stress and disease with respiratory disease as model system. The methodologies included in this review span traditional epidemiological, behavioral and immunological studies to current high throughput genomic, proteomic, metabolomic/metabonomic approaches. With the advent of various newer omics and bioinformatics methodologies we postulate that it will become feasible to understand the mechanisms through which stress can influence disease onset. Although the literature in this area is limited because of the infancy of this research area, the objective of this review is to illustrate the power of new approaches to address complex biological questions. These new approaches will also aid in our understanding how these processes are related to the dynamics and kinetics of changes in expression of multiple genes at various levels. PMID- 20360885 TI - Perceived nervousness and moodiness associated with increased CVD but not cancer morbidity in pre- and postmenopausal women. Observations from the Population Study of Women in Gothenburg, Sweden. AB - A 32-year prospective observational study was initiated in 1968, including 1462 women aged 60, 54, 50, 46, and 38, representative of the female population in these age groups. Measures included self-reported nervous symptoms and moodiness at baseline, menopausal status, risk factors as smoking, s-cholesterol, s triglycerides, body mass index (BMI), waist-hip ratio (WHR), blood pressure, and socioeconomic status (SES). The prevalence of nervousness and moodiness was investigated as well as if these reported symptoms could predict mortality and morbidity within 32 years in pre-and postmenopausal women. Women who reported at least two of the symptoms suffered from an increased risk of 32-year mortality, independent of all background variables described above (hazard ratio [HR] = 1.28, confidence interval [CI] 1.03-1.58). Women with only one of the nervous symptoms already had an increased risk of suffering from cardiovascular disease (CVD) also after multivariable adjustment (HR = 1.29, CI 1.09-1.52) a risk that also remained significant when analyzing CVD risk in the group of premenopausal women (HR = 1.28, CI 1.02-1.62). There was no significantly increased risk among pre-or postmenopausal women with perceived nervousness/moodiness of developing cancer during the 32-year follow-up. There seems to be an association between nervousness/ moodiness and premature mortality and morbidity in CVD, especially when present already in the premenopausal state in women. PMID- 20360887 TI - Prevalence of hypersexual behavior in Parkinson's disease patients: Not restricted to males and dopamine agonist use. AB - This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson's disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported. PMID- 20360886 TI - Unlike the synchronous Plasmodium falciparum and P. chabaudi infection, the P. berghei and P. yoelii asynchronous infections are not affected by melatonin. AB - We have previously reported that Plasmodium chabaudi and P. falciparum sense the hormone melatonin and this could be responsible for the synchrony of malaria infection. In P. chabaudi and P. falciparum, melatonin induces calcium release from internal stores, and this response is abolished by U73122, a phospholipase C inhibitor, and luzindole, a melatonin-receptor competitive antagonist. Here we show that, in vitro, melatonin is not able to modulate cell cycle, nor to elicit an elevation in intracellular calcium concentration of the intraerythrocytic forms of P. berghei or P. yoelii, two rodent parasites that show an asynchrononous development in vivo. Interestingly, melatonin and its receptor do not seem to play a role during hepatic infection by P. berghei sporozoites either. These data strengthen the hypothesis that host-derived melatonin does not synchronize malaria infection caused by P. berghei and P. yoelii. Moreover, these data explain why infections by these parasites are asynchronous, contrary to what is observed in P. falciparum and P. chabaudi infections. PMID- 20360888 TI - Long-term radiotherapy related complications in children with head and neck cancer: Another era for pediatric oncologic pathology. AB - Long-term radiotherapy-related complications in children with head and neck cancer have been frequently reported, especially facial growth disorders and dental abnormalities. We report on two male children (8 and 14 years old) with head and neck cancer, who were successfully treated with chemoradiotherapy and presented with growth deficiency of middle face and mandible hypoplasia, eight years and one year later, respectively. These severe growth complications attributed to chemoradiotherapy, while the patients survived primary malignancy. Patient age at irradiation was significantly correlated with the severity of disorders. We consider late sequelae in children with head and neck cancer due to chemoradiotherapy another era for pediatric oncologic pathology for prevention, if possible, or to manage them efficiently. PMID- 20360889 TI - Acute inflammation at a mandibular solitary horizontal incompletely impacted molar. AB - Acute inflammation is frequently seen in the elderly around incompletely impacted molars located apart from molars or premolars. To identify the factors causing acute inflammation in the solitary molars without second molars or without second and first molars, ages of patients and rates of acute inflammation in 75 horizontal incompletely impacted mandibular molars in contact or not in contact with molars in subjects 41 years old or older were studied using orthopantomographs. Acute inflammation was seen in nine third molars out of 48 third molars in contact with second molars (18.8%), whereas acute inflammation was seen in 11 molars out of 19 solitary molars without second molars or without first and second molars (57.9%) (p < 0.01). The mean age of 48 subjects with third molars in contact with the second molar was 50.42 +/- 7.62 years, and the mean age of 19 subjects with isolated molars was 65.16 +/- 10.41 years (p < 0.0001). These indicate that a solitary horizontal incompletely impacted molar leads more frequently to acute inflammation along with aging due to possible bone resorption resulting from teeth loss. PMID- 20360890 TI - A 'brain tumor' in an intravenous drug abuser. AB - A male intravenous drug abuser who was infected with hepatitis B and C, presented with a slowly progressive hemiplegia. Contrast enhanced computerized tomography of the head showed a solitary ring-enhanced mass with surrounding edema. Clinically brain tumor was suspected but a brain biopsy confirmed cerebral toxoplasmosis. An HIV test was not considered until the result of brain biopsy. He also had lymphopenia and positive serum toxoplasma antibody. His subsequent HIV test was positive. He deteriorated after a brain biopsy. Empirical antitoxoplasma treatment is recommended in HIV-positive patients with ring enhanced lesions with surrounding edema and with positive toxoplasma serology. Cerebral toxoplasmosis is still the commonest cerebral opportunistic infection in HIV-infected patients even though the incidence has declined with the use of antiretroviral therapy. It is often diagnosed in those patients as an initial presentation of HIV infection or in those who failed to attend for disease monitoring. Clinical features and differential diagnosis of cerebral toxoplasmosis in immunocompromised patients are discussed. PMID- 20360891 TI - Anti-inflammatory effects of hyaluronan in arthritis therapy: Not just for viscosity. AB - Hyaluronic acid (HA) has been widely used for viscosupplementation of diseased or aged articular joints. However, recent investigations have revealed the active anti-inflammatory or chondroprotective effect of HA, suggesting its potential role in attenuation of joint damage. In particular, interactions between HA and other inflammatory mediators are attracting interest. This review summarizes several aspects of recent investigations of the anti-inflammatory effects of HA in arthritis. PMID- 20360892 TI - Treatment for intractable anemia with the traditional Chinese medicines Hominis Placenta and Cervi Cornus Colla (deer antler glue). AB - OBJECTIVE: Intractable anemia, such as aplastic anemia or that presumably associated with chronic herpes virus infections, sometimes require bone marrow transplant. We investigated the use of traditional Chinese medicine (TCM) for the treatment of intractable anemia. METHOD: Placenta Hominis (PH), steam boiled and roasted, and Cervi Cornus Colla (deer antler glue) has been used in China for hundreds of years to treat anemia. After consent was obtained, we prescribed these two materials for a 74-year-old female with aplastic anemia and a 26-year old male with presumably a virus-induced anemia. Concomitant conventional therapy was continued in both patients as prescribed by their respective attending physicians. CONCLUSION: Conventional therapy with steroid hormones, immunosuppressive drugs, platelet and erythrocyte transfusions were not effective in these patients. In addition, both patients suffered from serious side effects. In two patients, ingestion of Placenta Hominis and Cervi Cornus Colla with TCM prescriptions increased the platelet and enhanced the hemoglobin concentration in several months of therapy accompanied by a dramatic improvement in quality of life. The addition to conventional therapy of PH and Cervi Cornus Colla, the latter of which is very easy to obtain, may be one of the potentially advantageous choices in case of otherwise intractable anemia. PMID- 20360893 TI - Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy. AB - Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option. PMID- 20360894 TI - The prevalence of renal impairment in the elderly hospitalized population. AB - Renal impairment has already been cited as being under-reported. A retrospective cross-sectional study was carried out. The sample population consisted of 94 inpatients aged over 60 years at Clayponds Hospital in the UK who had been admitted for rehabilitation from acute hospitals. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault formula modified for SI units. Renal impairment was found in 95.7% (95% CI: 91.8-99.6) of the sample (GFR < 90 ml/min). The study confirms that undetected renal impairment is prevalent. What is significant is that all of the subjects in this study were admitted from acute hospitals to Clayponds Hospital for rehabilitation. It is recommended that more attention be paid to the identification of patients with renal failure in hospitals owing to its significant morbidity and mortality. PMID- 20360895 TI - Primary care assessment instruments for patients at risk of, or with, persistent pain: opportunistic findings from a systematic literature review. AB - BACKGROUND: Early identification in primary care settings of individuals with, or at-risk of, developing persistent pain, is important to limit development of disability. There is little information to assist primary care providers to choose or deliver relevant, efficient, and soundly constructed assessment instruments for this purpose. OBJECTIVE: We recently published the findings of a literature review, which produced a compendium of assessment instruments to identify adults with, or at-risk of developing, persistent pain of noncancer origin. This paper reports on instruments opportunistically identified during this review which may be appropriate to primary health care settings for early identification of such patients. RESULTS: One hundred sixteen potentially useful instruments were initially identified in the review, measuring pain severity, psychological distress, functional capacity, quality of life or multidimensional constructs of persistent pain. Following a series of steps, 45 instruments were shortlisted, with sound clinical utility and strong psychometric properties. Of these, 16 instruments were appropriate to primary health care settings because of simple wording, brief items, short administration time, and ease of scoring. CONCLUSION: No one assessment instrument captured all constructs of persistent pain. The 16 instruments provide a broad choice for primary care clinicians to assist with early identification of adults at risk of, or with persistent pain. PMID- 20360896 TI - Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. AB - The clinical benefits of endocrine therapy for patients with hormonosensitive breast cancer are well established. For many years, 5 years of tamoxifen was the gold standard of adjuvant treatment. The recent development of new endocrine agents provides physicians with a more effective therapeutic approach. Nevertheless, the success of neoadjuvant endocrine therapy is much more recent and less reported in the literature. This article reviews the studies published about neoadjuvant endocrine treatment (tamoxifen and aromatase inhibitors). According to the literature, neoadjuvant endocrine therapy seems to be effective. In contrast to neoadjuvant chemotherapy, neoadjuvant endocrine therapy is well tolerated, with very few patients having to discontinue the treatment because of side effects. It does not constitute a standard treatment but could have potential for elderly women with operable, hormonosensitive, well differentiated and slowly progressing (SBR I) tumor or for patients with lobular MSBR 1 carcinoma (low chemosensitivity). The newer generation of aromatase inhibitors (letrozole, anastrozole, exemestane) appears to be more active (in terms of overall response rates and conservative surgery rate) than tamoxifen. Patients with an estrogen receptor Allred score of 6 and over are more likely to respond and gain a clinical benefit. The optimal duration of neoadjuvant therapy has not yet been investigated in detail. These preliminary results should be confirmed by further studies. PMID- 20360897 TI - Intima-media thickness evolution after treatment with infliximab in patients with rheumatoid arthritis. AB - BACKGROUND: Atherosclerosis is a well known progressive disease that recognizes risk factors such as diabetes, hypertension, smoking, dyslipidemia, and inflammation. Mechanisms underlying atherosclerotic processes during inflammation are not completely understood, but cytokines are also involved, in particular tumor necrosis factor-alpha (TNF-alpha). Chronic inflammatory diseases such as rheumatoid arthritis (RA) are commonly associated with atherosclerotic complication. Little is known about the role of treatment of chronic inflammatory disease on the evolution of atherosclerosis in this kind of disease. Usually, evolution of atherosclerosis is monitored by intima-media thickness and the presence of plaques on several arteries such as common carotid. AIM: The aim of the study was to monitor atherosclerosis evolution in seven RA patients on common treatment with infliximab (an anti-TNF-alpha drug) compared with seven RA patients during common treatment but not treated with infliximab. PATIENTS AND METHODS: We selected 14 patients with RA according to the American College of Rheumatology classification criteria. Seven patients were selected before and after common treatment for RA based on nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and steroids (12 months), and seven patients before and after treatment based on infliximab associated with NSAIDs, methotrexate, and steroids (12 months). Ultrasound vascular imaging was performed to screen intima media thickness and the presence of atherosclerotic plaques on common carotid artery and identify evolution of atherosclerosis. RESULTS: After 12 months, patients that were treated with infliximab showed significant worsening of atherosclerosis with an increase of intima-media thickness and the presence of further atherosclerotic plaques compared to patients that were treated traditionally and showed a nonsignificant increase of the same parameters. DISCUSSION: Treatment based on anti-TNF-alpha such as infliximab shows a worsening evolution of atherosclerosis based on our data. If these data are associated with a poor clinical outcome such as atherothrombosis of cerebral vessels and/or coronary vessels, this should be evaluated by further studies. PMID- 20360898 TI - Ambulatory recorded ST segment depression on ECG is associated with lower cognitive function in healthy elderly men. AB - ST segment depression (STDE) has been found to be associated with cardiovascular disease in the elderly. Studies of the relation of ambulatory STDE to cognitive function in elderly persons aged 80 years or above is lacking. OBJECTIVE: To study the association between STDE and cognition. DESIGN AND PARTICIPANTS: A cross-sectional cohort study of 88 81-year-old men from the population study "Men born in 1914" investigated in an outpatient research clinic. Measurements included ambulatory 24-hour electrocardiogram (ECG) monitoring and a cognitive test battery of six tests. Proportion of lower cognitive function was calculated for each test in relation to STDE during the day and at night-time. RESULTS: Fifty-eight percent of the men had STDE and a higher proportion with low visuospatial cognitive function was found among those with STDE compared to the others (84% vs 59%; p = 0.014). A significant trend was noted for subjects without STDE compared to STDE night-time less than 60 minutes and night-time more than 60 minutes for spatial and verbal cognitive functions (p = 0.022). No trends were noted for STDE daytime. Maximal STDE during night showed similar association to spatial function (Benton Visual Retention test, r = -0.26; p = 0.028). Even when seven subjects with a history of stroke were excluded, the occurrence of STDE was associated to lower visuospatial cognitive function compared to those without STDE (87% vs 57%; p = 0.004). CONCLUSION: ST segment depression on ECG is common among elderly men and might be a vascular risk factor for cognitive deterioration. PMID- 20360899 TI - Duloxetine in the treatment of generalized anxiety disorder. AB - Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) which is FDA approved for the treatment of generalized anxiety disorder (GAD) in doses of 30 mg to 120 mg daily. Duloxetine has been shown to significantly improve symptoms of GAD as measured through the Hamilton Anxiety Rating Scale (HAMA), the Clinical Global Impressions Scale (CGI-I), and other various outcome measures in several placebo-controlled, randomized, double blind, multi-center studies. Symptom improvement began within the first few weeks, and continued for the duration of the studies. In addition, duloxetine has also been shown to improve outcomes in elderly patients with GAD, and in GAD patients with clinically significant pain symptoms. Duloxetine was noninferior compared with venlafaxine XR. Duloxetine was found to have a good tolerability profile which was predictable and similar to another SNRI, venlafaxine. Adverse events (AEs) such as nausea, constipation, dry mouth, and insomnia were mild and transient, and occurred at relatively low rates. It was found to have a low frequency of drug interactions. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of GAD, and has a predictable tolerability profile, with AEs generally being mild to moderate. PMID- 20360900 TI - Mental and somatic symptoms related to suicidal ideation in patients visiting a psychosomatic clinic in Japan. AB - Patients with suicidal ideation (SI) have various mental or somatic symptoms. A questionnaire-based interview elicited details concerning mental and somatic symptoms in patients visiting a psychosomatic clinic in Japan. Univariate logistic regression analyses followed by multiple regression models using a stepwise method were selected for identifying the candidate symptoms. Overall, symptoms related to depression were associated with SI in both sexes. Although women showed more various somatic symptoms associated with SI than men, many of those associations were diminished once severity of the depression was controlled. The current results suggest that a variety of self-reported symptoms, mainly related to depression, might reveal suicidal risk in outpatients with an urban hospital clinical setting. PMID- 20360901 TI - Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens. AB - A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI) pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%), Escherichia coli (26.3%), and Proteus spp. (17.1%). Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase), Staphylococcus aureus (9.8%), and E. coli (9.7%). The highest potency was exhibited by ciprofloxacin (91.2%), levofloxacin (89.2%), and moxifloxacin (85.1%), while there were high rates of resistance to nalidixic acid (51.7%) and pefloxacin (29.0%). Coliforms, particularly E. coli (>45%), remain the most prevalent causative agents of UTI while females within the age range of 20-50 years were most vulnerable to UTI. PMID- 20360902 TI - Determination of single-nucleotide polymorphism in the proximal promoter region of apolipoprotein M gene in coronary artery diseases. AB - OBJECTIVE: It has been reported that single-nucleotide polymorphism (SNP) in the proximal promoter region of apolipoprotein M (apoM) gene may confer the risk in the development of type 2 diabetes (T2D) and coronary artery disease (CAD) in the Han Chinese. However, in a recent study demonstrated that plasma apoM level did not correlated to the coronary heart disease. In the present studies, we investigated the SNP T-778C of apoM gene in CAD patients and controls in the Han Chinese population. Moreover we examined whether serum apoM levels could be influenced by this promoter mutation. MATERIAL AND METHODS: One hundred twenty six CAD patients and 118 non-CAD patients were subjected in the present study. All patients were confirmed by the angiography. The genotyping of polymorphisms T 778C in apoM promoter was determined by real-time polymerase chain reaction. Serum apoM levels were semi-quantitatively determined by the dot-blotting analysis. RESULTS: Distribution of apoM T-778C genotype in non-CAD patients was as following: 84.7% were T/T, 15.3% were T/C and 0.0% was C/C. T allele frequencies were 92.4% and C allele, 7.6%. In the CAD patients, 99 patients (78.6%) had the T/T genotype, 25 patients (19.8%) with T/C genotype and 2 patients (1.6%) with C/C genotype. The allele frequency was 88.5% for the T allele and 11.5% for the C allele. There was no statistical significant difference of serum apoM levels found in these three genotypes. CONCLUSIONS: There was no significant difference in allele or genotype frequencies between CAD patients and non-CAD patients. Binary logistic regression analysis with adjustments for age, gender, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, apoAI, apoB, and LP(a) indicated that the TC and CC genotypes in SNP T-778C were not significantly associated with the development of CAD (odds ratio = 1.510, 95% confidence interval: 0.756-3.017; p = 0.243). PMID- 20360903 TI - The use of spirometry in a primary care setting. AB - OBJECTIVE: To determine the use of spirometry in family practice, internal medicine, and pediatric outpatient settings. METHODS: Data were collected from 45 outpatient offices in the central Pennsylvania area via phone survey that asked a set of four questions: 1) Do you have spirometry in your office? 2) Do you use spirometry for asthma patients? 3) In what situation do you use spirometry for? 4) Do you use spirometry more for chronic obstructive pulmonary disease (COPD) or asthma? RESULTS: It was found that pediatricians used spirometry 66% of the time, family practitioners 47% of the time, and internal medicine practitioners 60% of the time. Of those who did not use spirometry, 94% stated that they refer to a hospital if they required spirometry and 6% referred to subspecialists if the patient required spirometry. 10% of pediatricians performed the test on each asthma visit, otherwise the others used it only for exacerbations or as a baseline. No internists used spirometry regularly for asthma patients, and 22% used it more for COPD. In family practice only 14% used spirometry routinely at each visit for asthma patients. CONCLUSIONS: Pediatricians used spirometry more often in the outpatient setting than other specialists, followed closely by internal medicine physicians. Family practice physicians were the least likely to use spirometry. Multiple barriers seemed to prevent routine use of spirometry, but no one barrier accounted for the majority. PMID- 20360904 TI - Development of a vaccine to prevent Japanese encephalitis: a brief review. AB - Japanese encephalitis (ICD 10: A83.0) is an important specific viral encephalitis caused by the Japanese encephalitis virus, a virus of the Flavivirus group. Millions of people, especially those in endemic areas of developing countries in Asia, are at high risk from this infection. Therefore proper management to deal with this virus is essential. There is no specific treatment for Japanese encephalitis virus. Supportive and symptomatic treatments are usually used, which emphasize the importance of prevention in this specific neurological disorder. Vector control or vaccination can be used to prevent the disease. Because the existing Japanese encephalitis vaccine poses some undesirable problems, a new vaccine is needed. The process of developing a new vaccine is briefly discussed. PMID- 20360905 TI - Delirium, a 'confusing' condition in general hospitals: The experience of a Consultation-Liaison Psychiatry Unit in Greece. AB - BACKGROUND/AIMS: A plethora of studies showed that delirium is common in hospitalized populations. We aimed to examine the characteristics of delirium patients referred to our Consultation-Liaison Psychiatry Unit (CLPU). METHODS: Our CLPU database was used to obtain data of all referred patients admitted to our hospital and diagnosed with delirium. All referred nondelirious patients served as controls. RESULTS: During one year, 483 patients were referred to the CLPU. Ninety-three (19.3%) were diagnosed with delirium. Delirious patients were older than nondelirious patients (P < 0.001), with 76.3% aged over 70 years. The majority of the referrals came from surgical specialties. Common etiological factors were fluid and electrolyte imbalance (29%), fractures (28%) and infections (24%), but laboratory tests for the investigation of the etiology prior to the consultation had been performed in only 12 patients (12.9%). The syndrome resulted in prolonged hospitalization and greater use of CLPU services. CONCLUSIONS: Referrals for delirium are frequent in CLPUs in Greece. Although delirium is common, it remains a 'confusing' condition for health practitioners. The under-diagnosis of delirium, the prolonged hospitalization and the time that the CLPU dedicated to these patients underlines the role of the CLPU psychiatrists in the management of the syndrome. PMID- 20360906 TI - Medical treatment of Cushing's disease: Overview and recent findings. AB - Cushing's disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing's disease measure <1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing's disease. PMID- 20360907 TI - Usefulness of inspiratory capacity measurement in COPD patients in the primary care setting. AB - OBJECTIVE: To determine if inspiratory capacity (IC) assessment could be useful for chronic obstructive pulmonary disease (COPD) patient management in the primary care setting. METHODS: A descriptive cross-sectional study was conducted in 93 patients diagnosed with COPD according to Spanish Thoracic Society (SEPAR) criteria. Patients were recruited in eight primary care centers in Andalusia, Spain. Anthropometric, sociodemographic, resting lung function (forced expiratory volume in one second [FEV(1)], forced vital capacity, synchronized vital capacity, IC), and quality of life data based on the Spanish version of Saint George's Respiratory Questionnaire (SGRQ) were obtained. RESULTS: LUNG FUNCTION RESULTS EXPRESSED AS PERCENTAGES OF THE PREDICTED VALUES WERE AS FOLLOWS: FEV(1), 49.04 (standard deviation [SD]: 16.23); IC, 61.73 (SD: 15.42). The SGRQ mean total score was 47.5 (SD 17.98). The Spearman's Rho correlation between FEV(1) and SGRQ was r = -0.36 (95% confidence interval [CI]: -0.529 to -0.166), between IC and SGRQ was r = -0.329 (95% CI -0.502 to -0.131), and between FEV(1) and IC was r = -0.561. CONCLUSIONS: Measurement of IC at rest could be used as a complementary functional exploration to forced spirometry in the monitorization of patients with COPD in the primary care setting. We found a poor correlation between IC and quality of life at the same level as in FEV(1). PMID- 20360909 TI - Screening of potential molecular targets for colorectal cancer therapy. AB - Colorectal cancer is a leading cause of cancer death worldwide. To identify molecular targets for colorectal cancer therapy, we tested small interfering RNAs (siRNAs) against 97 genes whose expression was elevated in human colorectal cancer tissues for the ability to promote apoptosis of human colorectal cancer cells (HT-29 cells). The results indicate that the downregulation of PSMA7 (proteasome subunit, alpha-type, 7) and RAN (ras-related nuclear protein) most efficiently induced apoptosis of HT-29 cells. PSMA7 and RAN were highly expressed in colorectal cancer cell lines compared with normal colon tissues. Furthermore, PSMA7 and RAN were overexpressed in not only colon tumor tissues but also the other tumor tissues. Moreover, in vivo delivery of PSMA7 siRNA and RAN siRNA markedly induced apoptosis in HT-29 xenograft tumors in mice. Thus, silencing of PSMA7 and RAN induces cancer cells to undergo apoptosis, and PSMA7 and RAN might be promising new molecular targets for drug and RNA interference-based therapeutics against colorectal cancer. PMID- 20360908 TI - Cellular assessment of muscle in COPD: case studies of two males. AB - The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD. PMID- 20360910 TI - An unusual presentation of an uncommon disease. AB - Extrapulmonary manifestations of sarcoidosis often go undiagnozed. Sarcoidosis should be considered in the differential diagnosis of cases presenting with parotid gland swelling, renal failure, and hypercalcemia. It's imperative to confirm the diagnosis with a tissue biopsy, as the condition is easily treatable with steroids. PMID- 20360911 TI - Update on the medical treatment of Graves' ophthalmopathy. AB - PURPOSE: To review recent advances in the understanding of Graves' ophthalmopathy (GO) pathogenesis as well as discuss current and future medical management strategies. DESIGN: Interpretive essay. METHODS: Literature review and interpretation. RESULTS: Medical treatment of GO has slowly evolved during the past few decades and has been hampered by a poor understanding of the disease at a cellular and molecular level. Current treatment recommendations and guidelines therefore focus on nonspecific immuno-suppression. Newer classes of treatment agents hold promise to more selectively target underlying cellular and molecular alterations in GO. CONCLUSION: Cooperation between individual patients, physicians and between differing medical centers, together with a refined understanding of the pathogenesis of GO, will lead to newer more-effective treatments for the disease and improve patient quality of life. PMID- 20360913 TI - Treatment of pathological synovial plicae of the knee. AB - OBJECTIVE: To analyze the incidence, clinical significance, and clinical manifestations of pathological synovial plicae of the knee. MATERIAL AND METHODS: Between 2002 and 2006, 63 patients with pathological synovial plicae of the knee were studied. Of those 63 patients, 21 had the diagnosis confirmed by previously performed magnetic resonance imaging. All of the patients initially underwent conservative treatment for 90 days that involved strengthening and improving the flexibility of the muscles surrounding the knee as well as modification of their sports activities. RESULTS: A total of 55 patients improved after conservative treatment. Six of these patients eventually experienced a recurrence of symptoms, but the symptoms were not incapacitating in any of these patients. The other eight patients underwent arthroscopic removal of the synovial plica. Of these eight patients, six returned to their pretreatment physical activities, and two had persistent symptoms during physical activity. CONCLUSION: The presence of a synovial plica of the knee should be considered as a potential diagnosis in patients with knee pain, especially those who practice sports inappropriately. Conservative treatment is effective in most cases, and surgical treatment should be reserved for exceptional cases that do not improve with conservative treatment. PMID- 20360914 TI - Delirium in hospitalized elderly patients and post-discharge mortality. AB - OBJECTIVE: To determine the impact of delirium on post-discharge mortality in hospitalized older patients. INTRODUCTION: Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality. METHODS: This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clinicas of Sao Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival. RESULTS: The sample included 199 patients, 66 (33%) of whom developed delirium (Group A). After one year, 33 (50%) group A patients had died, and 45 (33.8%) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post discharge mortality were age > or = 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007). CONCLUSION: Delirium is associated with higher post-discharge mortality as a dependent predictor. PMID- 20360915 TI - Primary cutaneous melanoma: an 18-year study. AB - BACKGROUND: Primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. OBJECTIVES: This study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. METHODS: Using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. Slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. RESULTS: The melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. In addition to Breslow's thickness and ulceration (p = 0.043 and p < 0.001, respectively), the mitotic rate per mm(2) also correlated with worse patient outcome (p = 0.0007). The sum of ulceration (0 when absent or 1 when present), the Breslow index (1 when <1 mm, 2 when >1 mm and <4 mm, 3 when >4 mm) and the mitotic index (0 when absent or 1 when > or =1 per mm(2)) allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7%) patients had systemic disease. The 5-year survival was approximately seventy percent. CONCLUSION: Because American Join Committee of Cancer Staging will update the classification of malignant tumors (TNM) staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. Additional studies are necessary to confirm the importance of a prognostic score as proposed herein. PMID- 20360916 TI - Effect of beta-blockers on the risk of atrial fibrillation in patients with acute myocardial infarction. AB - INTRODUCTION: Oral beta-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with beta-blockers could at least in part explain the benefits of this drug. OBJECTIVE: To investigate the effect of beta-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction. METHODS: We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral beta-blockers and mortality during the first 24 hours. RESULTS: a) The use of beta-blockers was inversely correlated with the presence of atrial fibrillation (rho = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (rho < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with beta-blockers and 6.7% in those who received the drug (rho < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, rho = 0.002). The use of beta-blockers was inversely and independently correlated with mortality (OR = 0.53; rho = 0.002). The patients who used beta-blockers showed a lower risk of atrial fibrillation (OR = 0.59; rho = 0.029) in the adjusted model. CONCLUSION: The presence of atrial fibrillation and the absence of oral beta-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral beta-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug's benefit. PMID- 20360917 TI - Intra-arterial blood pressure response in hypertensive subjects during low- and high-intensity resistance exercise. AB - OBJECTIVE: The aim of this study was to describe blood pressure responses during resistance exercise in hypertensive subjects and to determine whether an exercise protocol alters these responses. INTRODUCTION: Resistance exercise has been recommended as a complement for aerobic exercise for hypertensive patients. However, blood pressure changes during this kind of exercise have been poorly investigated in hypertensives, despite multiple studies of normotensives demonstrating significant increases in blood pressure. METHODS: Ten hypertensive and ten normotensive subjects performed, in random order, two different exercise protocols, composed by three sets of the knee extension exercise conducted to exhaustion: 40% of the 1-repetition maximum (1RM) with a 45-s rest between sets, and 80% of 1RM with a 90-s rest between sets. Radial intra-arterial blood pressure was measured before and throughout each protocol. RESULTS: Compared with normotensives, hypertensives displayed greater increases in systolic BP during exercise at 80% (+80 +/-3 vs. +62 +/-2 mmHg, P<0.05) and at 40% of 1RM (+75 +/-3 vs. +67 +/-3 mmHg, P<0.05). In both exercise protocols, systolic blood pressure returned to baseline during the rest periods between sets in the normotensives; however, in the hypertensives, BP remained slightly elevated at 40% of 1RM. During rest periods, diastolic blood pressure returned to baseline in hypertensives and dropped below baseline in normotensives. CONCLUSION: Resistance exercise increased systolic blood pressure considerably more in hypertensives than in normotensives, and this increase was greater when lower-intensity exercise was performed to the point of exhaustion. PMID- 20360918 TI - Anterograde removal of broken femoral nails without opening the nonunion site: a new technique. AB - OBJECTIVE: We describe a new technique for removing the distal fragments of broken intramedullary femoral nails without disturbing the nonunion site. METHODS: This technique involves the application of an AO distractor prior to the removal of the nail fragments, with subsequent removal of the proximal nail fragment in an anterograde fashion and removal of the distal fragment through a medial parapatellar approach. Impaction of the fracture site is then performed with a nail that is broader than the remaining fragmented material. RESULTS: Nails were removed from five patients using the technique described above without any complications. After a mean follow-up period of 61.8 months, none of these patients showed worsened knee osteoarthritis. CONCLUSION: The original technique described in this article allows surgeons to remove the distal fragment of fractured femoral intramedullary nails without opening the nonunion focus or using special surgical instruments. PMID- 20360919 TI - Total oxidant status, total antioxidant status, and paraoxonase and arylesterase activities during laparoscopic cholecystectomy. AB - INTRODUCTION: Laparoscopic cholecystectomy is the gold standard for the treatment of gallstone disease; however, adverse hemodynamic changes induced by increased intraabdominal pressure due to pneumoperitoneum are known to occur. Herein, we investigated the effects of pneumoperitoneum on oxidative stress markers, including paraoxonase, arylesterase, total oxidant status, and total antioxidant status, during laparoscopic cholecystectomy. PATIENTS AND METHODS: Patients that underwent a laparoscopic cholecystectomy were classified as Group I, whereas patients that underwent surgical procedures for an abdominal wall hernia under general anesthesia were classified as Group II. Blood samples were obtained during the preoperative period, the perioperative period, and 24 hours after surgery (postoperative day 1). Leukocyte counts, neutrophil rates, paraoxonase activities, arylesterase activities, and total oxidant and antioxidant status levels were measured. RESULTS: The differences in leukocyte counts and neutrophil rates were not significant between the two groups. In Group I, no significant differences in the total oxidant and antioxidant status levels were identified; however, paraoxonase and arylesterase levels were lower on postoperative day 1. No significant changes were observed in the total oxidant status, total antioxidant status, and paraoxonase or arylesterase activities in Group II. The perioperative total antioxidant status and arylesterase level were higher in Group I in comparison to Group II. CONCLUSION: Paraoxonase and arylesterase levels are useful markers in the evaluation of oxidative stress caused by intraabdominal pressure due to pneumoperitoneum. PMID- 20360920 TI - Electric countershock and cold stress effects on liver and adrenal gland. AB - OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300 mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to -8 degrees C temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats. PMID- 20360921 TI - Histological study of fresh versus frozen semitendinous muscle tendon allografts. AB - OBJECTIVE: The purpose of this study was to histologically analyze allografts from cadaveric semitendinous muscle after cryopreservation at -80 degrees C in comparison to a control group kept at only -4 degrees C to test the hypothesis that the histological characteristics of the tissue are maintained when the tendons are kept at lower temperatures. METHODS: In a tissue bank, 10 semitendinous tendons from 10 cadavers were frozen at -80 degress C as a storage method for tissue preservation. They were kept frozen for 40 days, and then a histological study was carried out. Another 10 tendon samples were analyzed while still "fresh". RESULTS: There was no histological difference between the fresh and frozen samples in relation to seven variables. CONCLUSIONS: Semitendinous muscle tendon allografts can be submitted to cryopreservation at -80 degrees C without suffering histological modifications. PMID- 20360922 TI - Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma. AB - INTRODUCTION: Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. OBJECTIVE: To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. METHOD: Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. RESULTS: All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. CONCLUSION: A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system. PMID- 20360923 TI - Beneficial effects of N-acetyl cysteine on pancreas and kidney following experimental pancreatic ischemia-reperfusion in rats. AB - OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11+/-0.55) and Group 2 (10.30+/-0.50) [p=0.0002] as well as between Group 2 (10.30+/-0.50) and Group 4 (7.82+/-0.38) [p=0.003]; creatinine levels between Group 1 (0.52 +/- 0.07) and Group 2 (0.77+/ 0.18) [p=0.035] as well as between Group 2 (0.77+/-0.18) and Group 3 (0.48+/ 0.13) [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27+/-0.96) and Group 2 (2.60+/-3.01) [p=0.026] as well as between Group 2 (2.60+/-3.01) and Group 4 (0.52+/-0.56) [p=0.002]. A decrease in pancreatic tissue GST-alpha3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006), and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively). CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model. PMID- 20360926 TI - Churg-strauss syndrome and active chronic hepatitis B virus infection: coincidence or association? PMID- 20360924 TI - Acute and chronic effects of aerobic and resistance exercise on ambulatory blood pressure. AB - Hypertension is a ubiquitous and serious disease. Regular exercise has been recommended as a strategy for the prevention and treatment of hypertension because of its effects in reducing clinical blood pressure; however, ambulatory blood pressure is a better predictor of target-organ damage than clinical blood pressure, and therefore studying the effects of exercise on ambulatory blood pressure is important as well. Moreover, different kinds of exercise might produce distinct effects that might differ between normotensive and hypertensive subjects.The aim of this study was to review the current literature on the acute and chronic effects of aerobic and resistance exercise on ambulatory blood pressure in normotensive and hypertensive subjects. It has been conclusively shown that a single episode of aerobic exercise reduces ambulatory blood pressure in hypertensive patients. Similarly, regular aerobic training also decreases ambulatory blood pressure in hypertensive individuals. In contrast, data on the effects of resistance exercise is both scarce and controversial. Nevertheless, studies suggest that resistance exercise might acutely decrease ambulatory blood pressure after exercise, and that this effect seems to be greater after low intensity exercise and in patients receiving anti-hypertensive drugs. On the other hand, only two studies investigating resistance training in hypertensive patients have been conducted, and neither has demonstrated any hypotensive effect. Thus, based on current knowledge, aerobic training should be recommended to decrease ambulatory blood pressure in hypertensive individuals, while resistance exercise could be prescribed as a complementary strategy. PMID- 20360927 TI - Mesenteric vasculitis in a systemic lupus erythematosus patient with a low sledai: an uncommon presentation. PMID- 20360925 TI - The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus. AB - Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus. PMID- 20360928 TI - Giant thrombosed venous aneurysm in the calf: MRI characteristics and the target sign. PMID- 20360929 TI - Effects of the modification of the aortic bifurcation geometry: a technical note regarding a novel model for experimental atherosclerotic and aneurysmatic lesions. PMID- 20360930 TI - Femoral mechanical-biological graft fixation in ACL reconstruction in young patients. PMID- 20360931 TI - Biomarker Development for the Clinical Activity of the mTOR Inhibitor Everolimus (RAD001): Processes, Limitations, and Further Proposals. AB - The mTOR inhibitor everolimus (RAD001, Afinitor) is an orally active anticancer agent. Everolimus demonstrates growth-inhibitory activity against a broad range of tumor cell histotypes in vitro and has the capacity to retard tumor growth in preclinical tumor models in vivo through mechanisms directed against both the tumor cell and the solid tumor stroma components. These properties have rendered it to be a clinically active drug, with subsequent registration in renal cell carcinoma (Motzer et al. [2008]. Lancet372, 449-456) as well as showing strong potential as a combination partner (Andre F et al. [2008]. J Clin Oncol26. Abstract 1003). Although everolimus has a high specificity for its molecular target, the ubiquitous nature of mTOR and the multifactorial influence that mTOR signaling has on cell physiology have made studies difficult on the identification and validation of a biomarker set to predict and monitor drug sensitivity for clinical use. In this review, a summary of the preclinical and clinical data relevant to biomarker development for everolimus is presented, and the advantages and problems of current biomarkers are reviewed. In addition, alternative approaches to biomarker development are proposed on the basis of examples of a combination of markers and functional noninvasive imaging. In particular, we show how basal levels of pAKT and pS6 together could, in principle, be used to stratify patients for likely response to an mTOR inhibitor. PMID- 20360932 TI - KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells. AB - The paracrine networks of the human melanoma microenvironment are able to influence tumor growth and progression. Among the paracrine growth factors involved in skin homeostasis, the KGF/FGF7 secreted by dermal fibroblasts promotes the epidermal proliferation and differentiation as well as the release from keratinocytes of other paracrine mediators. To evaluate the possible role played by KGF in affecting the behavior of different subtypes of melanoma carrying activating mutations or overexpression of the SCF receptor c-KIT, we used human melanoma cell lines, characterized by different expression levels of c KIT and opposing responsivity to SCF, and HaCaT keratinocytes. Quantitative real time reverse transcription-polymerase chain reaction assay and ELISA test on KGF treated keratinocytes showed enhanced expression and secretion of SCF in response to KGF and dependent on functional KGF receptor. Immunofluorescence microscopy and biochemical analysis showed, in one of the selected melanoma cell models, SCF dependent c-KIT activation induced by stimulation with the culture supernatants collected from KGF-treated keratinocytes. In keratinocyte-melanoma cocultures stained for the Ki67 proliferation marker, incubation with KGF induced enhanced growth not only of the keratinocytes but also of the melanoma cells, which could be blocked by the c-KIT inhibitor imatinib, demonstrating the establishment of a KGF-induced paracrine signaling network owing to the coexpression of biologically active SCF released from keratinocytes and functional c-KIT on melanoma cells. PMID- 20360933 TI - Expression of Long-chain Fatty Acyl-CoA Synthetase 4 in Breast and Prostate Cancers Is Associated with Sex Steroid Hormone Receptor Negativity. AB - Previous studies have shown that key enzymes involved in lipid metabolic pathways are differentially expressed in normal compared with tumor tissues. However, the precise role played by dysregulated expression of lipid metabolic enzymes and altered lipid homeostasis in carcinogenesis remains to be established. Fatty acid synthase is overexpressed in a variety of cancers, including breast and prostate. The purpose of the present study was to examine the expression patterns of additional lipid metabolic enzymes in human breast and prostate cancers. This was accomplished by analysis of published expression databases, with confirmation by immunoblot assays. Our results indicate that the fatty acid-activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), is differentially expressed in human breast cancer as a function of estrogen receptor alpha (ER) status. In 10 separate studies, ACSL4 messenger RNA (mRNA) was overexpressed in ER-negative breast tumors. Of 50 breast cancer cell lines examined, 17 (89%) of 19 ER positive lines were negative for ACSL4 mRNA expression and 20 (65%) of 31 ER negative lines expressed ACSL4 mRNA. The inverse relationship between ER expression and ACSL4 expression was also observed for androgen receptor status in both breast and prostate cancers. Furthermore, loss of steroid hormone sensitivity, such as that observed in Raf1-transfected MCF-7 cells and LNCaP-AI cells, was associated with induction of ACSL4 expression. Ablation of ACSL4 expression inMDA-MB-231 breast cancer cells had no effect on cell proliferation; however, sensitivity to the cytotoxic effects of triacsin C was increased three fold in the cells lacking ACSL4. PMID- 20360934 TI - Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma. AB - The transcription factor, nuclear factor kappaB (NF-kappaB), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-kappaB and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-kappaB activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-kappaB and IkappaB kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both IkappaB and phospho IkappaB was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-kappaB activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-kappaB reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP induced apoptosis in both cell lines. These data suggest that activation of NF kappaB and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF kappaB activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC. PMID- 20360935 TI - Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. AB - MicroRNA are small noncoding transcripts involved in many cellular mechanisms, including tumorigenesis. miR-210, in particular, is induced by hypoxia and correlates with adverse outcomes in certain cancers. Because pancreatic adenocarcinomas exhibit extremely hypoxic signatures, we hypothesized that miR 210 may serve as a diagnostic marker for screening or surveillance for pancreatic cancer. Plasma samples were obtained from newly diagnosed pancreatic cancer patients and age-matched noncancer controls. miRNA was extracted directly from plasma and reverse-transcribed to complementary DNA. A known quantity of synthetic Caenorhabditis elegans miR-54 (celmiR-54) was added for normalization. miR-210 and cel-miR-54 were then measured using quantitative reverse transcription polymerase chain reaction. An initial cohort of 11 pancreatic cancer patients and 14 age-matched controls was used as the test set and a second cohort of 11 pancreatic cancer patients and 11 controls was used as the validating set in this study. miR-210 was reliably detected and quantified, with a statistically significant four-fold increase in expression in pancreatic cancer patients compared with normal controls (P < .00004) in the test set. This difference was confirmed in the validation group (P < .018). In summary, circulating miR-210 levels are elevated in pancreatic cancer patients and may potentially serve as a useful biomarker for pancreatic cancer diagnosis. PMID- 20360936 TI - Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma. AB - The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human cancers in a PDT approach (Pa-PDT); however, the potential effect of Pa-PDT on the anticancer immunity has never been studied. In the present work, the underlying action mechanism of Pa-PDT was systemically investigated with a human hepatoma cell line HepG2. We found that Pa PDT significantly inhibited the growth of HepG2 cells with a half maximal inhibitory concentration/endoplasmic reticulum of 0.35 microM at 24 hours by the induction of apoptosis, as shown by externalization of phosphatidylserine, release of mitochondrial cytochrome c, and activation of the caspases cascade in the treated cells. Interestingly, using two-dimensional polyacrylamide gel electrophoresis analysis, a 57-kDa disulfide-isomerase-like ER resident protein (ERp57) that belongs to the HLA class I-restricted antigen-processing machinery was found to be mediated during the Pa-PDT treatment. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the confocal microscopic observation and immunoprecipitation assay. Nevertheless, the immunogenicity of HepG2 cells was increased by Pa-PDT treatment that triggered phagocytic capture by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and cancer immunity in the tumor host. PMID- 20360937 TI - Transferrin receptor 2 is frequently and highly expressed in glioblastomas. AB - Under physiological conditions, transferrin receptor 2 (TfR2) is expressed in the liver and its balance is related to the cell cycle rather than to intracellular iron levels. We recently showed that TfR2 is highly expressed in glioblastoma cell lines. Here, we demonstrate that, in these cells, TfR2 appears to localize in lipid rafts, induces extracellular signal-regulated kinase 1/2 phosphorylation after transferrin binding, and contributes to cell proliferation, as shown by RNA silencing experiments. In vitro hypoxic conditions induce a significant TfR2 up regulation, suggesting a role in tumor angiogenesis. As assessed by immunohistochemistry, the level of TfR2 expression in astrocytic tumors is related to histologic grade, with the highest expression observed in glioblastomas. The level of TfR2 expression represents a favorable prognostic factor, which is associated with the higher sensitivity to temozolomide of TfR2 positive tumor cells in vitro. The endothelial cells of glioblastoma vasculature also stain for TfR2, whereas those of the normal brain vessels do not. Importantly, TfR2 is expressed by the subpopulation of glioblastoma cells with properties of cancer-initiating cells. TfR2-positive glioblastoma cells retain their TfR2 expression on xenografting in immunodeficient mice. In conclusion, our observations demonstrate that TfR2 is a neoantigen for astrocytomas that seems attractive for developing target therapies. PMID- 20360938 TI - Intratumor administration of the photosensitizer pc 4 affords photodynamic therapy efficacy and selectivity at short drug-light intervals. AB - We evaluated intratumor (IT) versus intravenous (IV) administration of the photosensitizer Pc 4 with respect to tumor photosensitizer concentration, specificity, and responses to irradiation. BALB/c mice bearing intradermal EMT6 tumors were given 0.3 mg/kg Pc 4 injected IT or IV through the tail vein. Photosensitizer concentration was evaluated by chloroform extraction and localization assessed by fluorescence imaging and spectroscopy in vivo. Tumors were irradiated at 667 nm, 50 mW/cm(2), and 100 J/cm(2). Cures were defined as no palpable tumor 90 days after irradiation. Tumor Pc 4 concentrations 1 hour after IT administration were 35,000-fold higher than measured 24 hours after IV administration (0.112 vs 0.317 x 10(-5)microg Pc 4/mg tumor). Exquisite tumor selectivity was observed 1 hour after IT injection. Fluorescence imaging of freshly sectioned tumors revealed no regions devoid of sensitizer at this time point, with pixel intensities in a midline section within a factor of 3 of the peak intensity. For identical photosensitizer doses, IT administration significantly improved tumor responses to irradiation, with more than 70% of tumors cured with IT-Pc 4-PDT. In this model, IT-Pc 4 administration provides improved tumor control, greater selectivity, and opportunity for a short drug light interval. PMID- 20360939 TI - An approach to the study of gene expression in hepatocarcinogenesis initiation. AB - In carcinogenesis, determination of gene and protein expression profiles is important for prevention and treatment. Caffeic acid phenethyl ester (CAPE) in a single dose administered before carcinogenic initiation induced by diethylnitrosamine (DEN) prevents the appearance of preneoplastic lesions. On the basis of this approach, the main purpose of this work was to compare the gene expression profiles induced by DEN or a previously administered single dose of CAPE. Using a modified hepatocarcinogenesis-resistant hepatocyte model, male Fischer-344 rats were administered with one intraperitoneal dose of CAPE (20 mg/kg) 12 hours before DEN administration (200 mg/kg). Livers were removed and processed for microarray analysis and reverse transcription-polymerase chain reaction 12 hours after CAPE dosing and 24 hours after DEN administration with or without CAPE. CAPE alone did not alter the expression profile. DEN treatment modified the expression of 665 genes, and CAPE plus DEN induced changes in 1371 genes. DEN treatment increased the expression of genes associated with oxidative stress such as glutathione reductase, genes involved in cell cycle regulation including p53, and modified cytochrome P450. CAPE plus DEN diminished the expression of cytochrome involved in DEN bioactivation such as CYP2B1 as well as the expression of regulators of oxidative stress such as glutathione reductase, GST-kappa and GST-theta, and cell cycle regulators such as p53. Using CAPE as a tool, we uncovered new approaches for studying the altered expression of reactive genes and identifying proteins that will help to propose well-sustained and concrete hypothesis of DEN mechanism of hepatocarcinogenesis initiation. PMID- 20360940 TI - The extracellular matrix glycoprotein elastin microfibril interface located protein 2: a dual role in the tumor microenvironment. AB - We have recently reported that elastin microfibril interface located protein 2 (EMILIN2), an extracellular matrix (ECM) glycoprotein, triggers cell death through a direct binding to death receptors. EMILIN2 thus influences cell viability through a mechanism that is unique for an ECM molecule. In the present work, we report an additional function for this molecule. First, we identify the region responsible for the proapoptotic effects, a 90-amino acid residue-long coiled-coil fragment toward the N-terminus of the molecule. The fragment recapitulates EMILIN2 proapoptotic mechanisms. In addition, using either the full molecule or the active fragment, for the first time, we demonstrate a significant antitumoral effect in vivo, likely due to a decrease in tumor cell viability. Unexpectedly, tumors treated with EMILIN2 or the deletion mutant display a significant increase of tumor angiogenesis. In view of this novel finding, the cotreatment of the growing tumors with an antiangiogenic drug led, in most cases, to a complete regression of tumor growth. These results grant further support to recent findings that pinpoint the microenvironment as an important regulator of cell fate under both physiological and pathological conditions and disclose the possibility of using EMILIN2 fragments as potent antineoplastic tools for cancer treatment. PMID- 20360941 TI - A novel molecular diagnostic of glioblastomas: detection of an extracellular fragment of protein tyrosine phosphatase mu. AB - We recently found that normal human brain and low-grade astrocytomas express the receptor protein tyrosine phosphatase mu (PTPmu) and that the more invasive astrocytomas, glioblastoma multiforme (GBM), downregulate full-length PTPmu expression. Loss of PTPmu expression in GBMs is due to proteolytic cleavage that generates an intracellular and potentially a cleaved and released extracellular fragment of PTPmicro. Here, we identify that a cleaved extracellular fragment containing the domains required for PTPmicro-mediated adhesion remains associated with GBM tumor tissue. We hypothesized that detection of this fragment would make an excellent diagnostic tool for the localization of tumor tissue within the brain. To this end, we generated a series of fluorescently tagged peptide probes that bind the PTPmu fragment. The peptide probes specifically recognize GBM cells in tissue sections of surgically resected human tumors. To test whether the peptide probes are able to detect GBM tumors in vivo, the PTPmu peptide probes were tested in both mouse flank and intracranial xenograft human glioblastoma tumor model systems. The glial tumors were molecularly labeled with the PTPmu peptide probes within minutes of tail vein injection using the Maestro FLEX In Vivo Imaging System. The label was stable for at least 3 hours. Together, these results indicate that peptide recognition of the PTPmu extracellular fragment provides a novel molecular diagnostic tool for detection of human glioblastomas. Such a tool has clear translational applications and may lead to improved surgical resections and prognosis for patients with this devastating disease. PMID- 20360942 TI - Senescent fibroblasts promote neoplastic transformation of partially transformed ovarian epithelial cells in a three-dimensional model of early stage ovarian cancer. AB - Most epithelial ovarian cancers are diagnosed postmenopausally, although the well established epidemiological risk factors (parity, oral contraceptive use) are premenopausal. We hypothesized that accumulation of senescent fibroblasts, together with concomitant loss of presenescent fibroblasts within the ovarian cortex, promotes initiation and early development of ovarian cancer from ovarian surface epithelial (OSE) cells. To test this, we established immortalized OSE (IOSE) cell lines that mimic early neoplastic transformation by overexpressing the CMYC oncogene (IOSE(CMYC)) and normal ovarian presenescent (PSN) and senescent (SEN) fibroblast cell lines. We then evaluated the ability of PSN and SEN fibroblasts to transform IOSE and IOSE(CMYC) after coculture. SEN fibroblasts significantly enhanced neoplastic development of IOSE(CMYC) cells; there was an up to 15-fold increase in migration of IOSE(CMYC) cells cocultured with SEN fibroblasts compared with PSN fibroblasts. Conditioned medium from SEN fibroblasts promoted anchorage-independent growth of IOSE(CMYC) cells. We studied fibroblast-epithelial cell interactions in heterotypic three-dimensional spheroid models. Dual immunohistochemical staining of spheroids for a proliferation marker (MIB-1) and cytokeratin-18 indicated that SEN fibroblasts induce approximately a five-fold increase in proliferation of IOSE(CMYC) cells relative to cocultures with PSN fibroblasts. SEN, but not PSN fibroblasts, also induced nuclear atypia in epithelial cells in three-dimensional spheroids. These data suggest for the first time that the accumulation of senescent, or loss of presenescent fibroblasts, can promote neoplastic development of partially transformed OSE cells in vitro and illustrates the power of using three-dimensional heterotypic modeling to gain better insights into the etiology underlying the development of epithelial ovarian cancer. PMID- 20360943 TI - Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. AB - BACKGROUND: Lymphoid enhancer factor-1 (lef-1) is overexpressed in B-cell chronic lymphocytic leukemia (CLL) when compared with normal B cells and transcribes several genes implicated in the pathogenesis of CLL. We therefore hypothesize that antagonism of lef-1 might lead to killing of CLL cells. We used two small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling (CGP049090 and PKF115 584) to test our hypothesis. DESIGN AND METHODS: Enriched CLL cells and healthy B cells were used in this study. Small interfering RNA (siRNA)-mediated knockdown of lef-1 in primary CLL cells was done using nucleofection, and 50% lethal concentration (LC(50)) of two small molecules was assessed using ATP-based cell viability assay. Apoptotic response was investigated in time course experiments with different apoptotic markers. Specificity of the small molecules was demonstrated by coimmunoprecipitation experiments for the lef-1/beta-catenin interaction. In vivo studies were done in JVM-3 subcutaneous xenograft model. RESULTS: Inhibition of lef-1 by siRNA leads to increased apoptosis of CLL cells and inhibited proliferation of JVM-3 cell lines. The two small molecule inhibitors (CGP049090 and PKF115-584) efficiently kill CLL cells (LC(50)<1 microM), whereas normal B cells were not significantly affected. Coimmunoprecipitation showed a selective disruption of beta-catenin/lef-1 interaction. In vivo studies exhibited tumor inhibition of 69% with CGP049090 and 57% with PKF115-584 when compared with vehicle-treated controls, and the intervention was well tolerated. CONCLUSIONS: We have demonstrated that targeting lef-1 is a new and selective therapeutic approach in CLL. CGP049090 or PKF115-584 may be attractive compounds for CLL and other malignancies that deserve further (pre)clinical evaluation. PMID- 20360944 TI - Pigment epithelium-derived factor stimulates tumor macrophage recruitment and is downregulated by the prostate tumor microenvironment. AB - Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis but whether it has additional effects on the tumor microenvironment is largely unexplored. We show that overexpression of PEDF in orthotopic MatLyLu rat prostate tumors increased tumor macrophage recruitment. The fraction of macrophages expressing inducible nitric oxide synthase, a marker of cytotoxic M1 macrophages, was increased, suggesting that PEDF could enhance antitumor immunity. In addition, PEDF overexpression reduced vascular growth both in the tumor and in the surrounding normal tissue, slowed tumor growth, and decreased lymph node metastasis. Contrary, extratumoral lymphangiogenesis was increased. PEDF expression is, for reasons unknown, often decreased or lost during prostate tumor progression. When AT-1 rat prostate tumor cells, expressing high levels of PEDF messenger RNA (mRNA) and protein, were injected into the prostate, PEDF is markedly downregulated, suggesting that factors in the microenvironment suppressed its expression. One such factor could be macrophage-derived tumor necrosis factor alpha (TNFalpha). A fraction of the accumulating macrophages expressed TNFalpha, and TNFalpha treatment downregulated the expression of PEDF protein and mRNA in prostate AT-1 tumor cells in vitro and in the rat ventral prostate in vivo. PEDF apparently has multiple effects in prostate tumors: it suppresses angiogenesis and metastasis, but it also causes macrophage accumulation. Accumulating macrophages may inhibit tumor growth, but they may also suppress PEDF and enhance lymph angiogenesis and, in this way, eventually enhance tumor growth. PMID- 20360945 TI - The eIF4E/eIF4G interaction inhibitor 4EGI-1 augments TRAIL-mediated apoptosis through c-FLIP Down-regulation and DR5 induction independent of inhibition of cap dependent protein translation. AB - The small molecule 4EGI-1 was identified as an inhibitor of cap-dependent translation initiation owing to its disruption of the eIF4E/eIF4G association through binding to eIF4E. 4EGI-1 exhibits growth-inhibitory and apoptosis inducing activity in cancer cells; thus, we were interested in its therapeutic efficacy in human lung cancer cells. 4EGI-1, as a single agent, inhibited the growth and induced apoptosis of human lung cancer cells.When combined with the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), enhanced apoptosis-induced activity was observed. As expected, 4EGI-1 inhibited eIF4E/eIF4G interaction and reduced the levels of cyclin D1 and hypoxia-inducing factor-1alpha (HIF-1alpha), both of which are regulated by a cap-dependent translation mechanism. Moreover, 4EGI-1 induced CCAAT/enhancer-binding protein homologous protein-dependent DR5 expression and ubiquitin/proteasome- mediated degradation of cellular FLICE-inhibitory protein (c-FLIP). Small interfering RNA mediated blockade of DR5 induction or enforced expression of c-FLIP abrogated 4EGI-1's ability to enhance TRAIL-induced apoptosis, indicating that both DR5 induction and c-FLIP down-regulation contribute to enhancement of TRAIL-induced apoptosis by 4EGI-1. However, inhibition of eIF4E/eIF4G interaction by knockdown of eIF4E effectively reduced the levels of cyclin D1 and HIF-1alpha but failed to induce DR5 expression, downregulate c-FLIP levels, or augment TRAIL-induced apoptosis. These results collectively suggest that 4EGI-1 augments TRAIL-induced apoptosis through induction of DR5 and down-regulation of c-FLIP, independent of inhibition of cap-dependent protein translation. PMID- 20360946 TI - Molecules and mechanisms involved in the generation and migration of cortical interneurons. AB - The GABA (gamma-aminobutyric acid)-containing interneurons of the neocortex are largely derived from the ganglionic eminences in the subpallium. Numerous studies have previously defined the migratory paths travelled by these neurons from their origins to their destinations in the cortex. We review here results of studies that have identified many of the genes expressed in the subpallium that are involved in the specification of the subtypes of cortical interneurons, and the numerous transcription factors, motogenic factors and guidance molecules that are involved in their migration. PMID- 20360947 TI - A single nucleotide polymorphism in the Bax gene promoter affects transcription and influences retinal ganglion cell death. AB - Pro-apoptotic Bax is essential for RGC (retinal ganglion cell) death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2J(Bax+/-) mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax( /-) mice), but 129B6(Bax+/-) mice exhibited significant cell loss (similar to wild-type mice). The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T(129B6) to C(DBA/2J)) at position -515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53(-/-) cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA-protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli. PMID- 20360948 TI - Genetic relationships of ethnic minorities in Southwest China revealed by microsatellite markers. AB - Population migrations in Southwest and South China have played an important role in the formation of East Asian populations and led to a high degree of cultural diversity among ethnic minorities living in these areas. To explore the genetic relationships of these ethnic minorities, we systematically surveyed the variation of 10 autosomal STR markers of 1,538 individuals from 30 populations of 25 ethnic minorities, of which the majority were chosen from Southwest China, especially Yunnan Province. With genotyped data of the markers, we constructed phylogenies of these populations with both D(A) and D(C) measures and performed a principal component analysis, as well as a clustering analysis by structure. Results showed that we successfully recovered the genetic structure of analyzed populations formed by historical migrations. Aggregation patterns of these populations accord well with their linguistic affiliations, suggesting that deciphering of genetic relationships does in fact offer clues for study of ethnic differentiation. PMID- 20360950 TI - Environmental factors associated with the distribution of Anopheles gambiae s.s in Ghana; an important vector of lymphatic filariasis and malaria. AB - Anopheles gambiae s.s mosquitoes are important vectors of lymphatic filariasis (LF) and malaria in Ghana. To better understand their ecological aspects and influence on disease transmission, we examined the spatial distribution of the An. gambiae (M and S) molecular forms and associated environmental factors, and determined their relationship with disease prevalence. Published and current data available on the An. gambiae species in Ghana were collected in a database for analysis, and the study sites were georeferenced and mapped. Using the An. gambiae s.s sites, environmental data were derived from climate, vegetation and remote-sensed satellite sources, and disease prevalence data from existing LF and malaria maps in the literature. The data showed that An. gambiae M and S forms were sympatric in most locations. However, the S form predominated in the central region, while the M form predominated in the northern and coastal savanna regions. Bivariate and multiple regression analyses identified temperature as a key factor distinguishing their distributions. An. gambiae M was significantly correlated with LF, and 2.5 to 3 times more prevalent in the high LF zone than low to medium zones. There were no significant associations between high prevalence An. gambiae s.s locations and malaria. The distribution of the An. gambiae M and S forms and the diseases they transmit in Ghana appear to be distinct, driven by different environmental factors. This study provides useful baseline information for disease control, and future work on the An. gambiae s.s in Ghana. PMID- 20360949 TI - T cell-dependence of Lassa fever pathogenesis. AB - Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development. PMID- 20360951 TI - A spontaneous dominant-negative mutation within a 35S::AtMYB90 transgene inhibits flower pigment production in tobacco. AB - BACKGROUND: In part due to the ease of visual detection of phenotypic changes, anthocyanin pigment production has long been the target of genetic and molecular research in plants. Specific members of the large family of plant myb transcription factors have been found to play critical roles in regulating expression of anthocyanin biosynthetic genes and these genes continue to serve as important tools in dissecting the molecular mechanisms of plant gene regulation. FINDINGS: A spontaneous mutation within the coding region of an Arabidopsis 35S::AtMYB90 transgene converted the activator of plant-wide anthocyanin production to a dominant-negative allele (PG-1) that inhibits normal pigment production within tobacco petals. Sequence analysis identified a single base change that created a premature nonsense codon, truncating the encoded myb protein. The resulting mutant protein lacks 78 amino acids from the wild type C terminus and was confirmed as the source of the white-flower phenotype. A putative tobacco homolog of AtMYB90 (NtAN2) was isolated and found to be expressed in flower petals but not leaves of all tobacco plants tested. Using transgenic tobacco constitutively expressing the NtAN2 gene confirmed the NtAN2 protein as the likely target of PG-1-based inhibition of tobacco pigment production. CONCLUSIONS: Messenger RNA and anthocyanin analysis of PG-1Sh transgenic lines (and PG-1Sh x purple 35S::NtAN2 seedlings) support a model in which the mutant myb transgene product acts as a competitive inhibitor of the native tobacco NtAN2 protein. This finding is important to researchers in the field of plant transcription factor analysis, representing a potential outcome for experiments analyzing in vivo protein function in test transgenic systems that over-express or mutate plant transcription factors. PMID- 20360952 TI - Extra N-terminal residues have a profound effect on the aggregation properties of the potential yeast prion protein Mca1. AB - The metacaspase Mca1 from Saccharomyces cerevisiae displays a Q/N-rich region at its N-terminus reminiscent of yeast prion proteins. In this study, we show that the ability of Mca1 to form insoluble aggregates is modulated by a peptide stretch preceding its putative prion-forming domain. Based on its genomic locus, three potential translational start sites of Mca1 can give rise to two slightly different long Mca1 proteins or a short version, Mca1(451/453) and Mca1(432,) respectively, although under normal physiological conditions Mca1(432) is the predominant form expressed. All Mca1 variants exhibit the Q/N-rich regions, while only the long variants Mca1(451/453) share an extra stretch of 19 amino acids at their N-terminal end. Strikingly, only long versions of Mca1 but not Mca1(432) revealed pronounced aggregation in vivo and displayed prion-like properties when fused to the C-terminal domain of Sup35 suggesting that the N-terminal peptide element promotes the conformational switch of Mca1 protein into an insoluble state. Transfer of the 19 N-terminal amino acid stretch of Mca1(451) to the N terminus of firefly luciferase resulted in increased aggregation of luciferase, suggesting a protein destabilizing function of the peptide element. We conclude that the aggregation propensity of the potential yeast prion protein Mca1 in vivo is strongly accelerated by a short peptide segment preceding its Q/N-rich region and we speculate that such a conformational switch might occur in vivo via the usage of alternative translational start sites. PMID- 20360953 TI - Distance estimation is influenced by encoding conditions. AB - BACKGROUND: It is well established that foveating a behaviorally relevant part of the visual field improves localization performance as compared to the situation where the gaze is directed elsewhere. Reduced localization performance in the peripheral encoding conditions has been attributed to an eccentricity-dependent increase in positional uncertainty. It is not known, however, whether and how the foveal and peripheral encoding conditions can influence spatial interval estimation. In this study we compare observers' estimates of a distance between two co-planar dots in the condition where they foveate the two sample dots and where they fixate a central dot while viewing the sample dots peripherally. METHODOLOGY/PRINCIPAL FINDINGS: Observers were required to reproduce, after a short delay, a distance between two sample dots based on a stationary reference dot and a movable mouse pointer. When both sample dots are foveated, we find that the distance estimation error is small but consistently increases with the dots separation size. In comparison, distance judgment in peripheral encoding condition is significantly overestimated for smaller separations and becomes similar to the performance in foveal trials for distances from 10 to 16 degrees. CONCLUSIONS/SIGNIFICANCE: Although we find improved accuracy of distance estimation in the foveal condition, the fact that the difference is related to the reduction of the estimation bias present in the peripheral condition, challenges the simple account of reducing the eccentricity-dependent positional uncertainty. Contrary to this, we present evidence for an explanation in terms of neuronal populations activated by the two sample dots and their inhibitory interactions under different visual encoding conditions. We support our claims with simulations that take into account receptive fields size differences between the two encoding conditions. PMID- 20360956 TI - Diversity partitioning of stony corals across multiple spatial scales around Zanzibar Island, Tanzania. AB - BACKGROUND: The coral reefs of Zanzibar Island (Unguja, Tanzania) encompass a considerable proportion of the global coral-reef diversity and are representative of the western Indian Ocean region. Unfortunately, these reefs have been recently subjected to local and regional disturbances. The objectives of this study were to determine whether there are potentially non-random processes forcing the observed coral diversity patterns, and highlight where and at which spatial scales these processes might be most influential. METHODOLOGY/PRINCIPAL FINDINGS: A hierarchical (nested) sampling design was employed across three spatial scales, ranging from transects (T (R124C) point mutation was found in exon 4 of TGFBI in all six members of the pedigree affected with RBCD, but not in the unaffected members. CONCLUSIONS: Within this pedigree, RBCD segregates with the R124C variance, which is a known mutation for lattice corneal dystrophy type I. Therefore, along with G623D and R124L, the R124C mutation in TGFBI is also found to be responsible for RBCD. PMID- 20360993 TI - Candidate gene study to investigate the genetic determinants of normal variation in central corneal thickness. AB - PURPOSE: The genetic component underlying variation in central corneal thickness (CCT) in the normal population remains largely unknown. As CCT is an identified risk factor for open-angle glaucoma, understanding the genes involved in CCT determination could improve our understanding of the mechanisms involved in this association. METHODS: To identify novel CCT genes, we selected eight different candidates based on a range of criteria. These included; aquaporin 1 (AQ1), aquaporin 5 (AQ5), decorin (DCN), fibrillin-1 (FBN1), keratocan (KERA), lumican (LUM), osteoglycin (OGN), and paired box 6 (PAX6). Tagging single nucleotide polymorphisms (SNPs) selected from the HapMap database were genotyped to cover the majority of genetic variation within each gene. Each SNP was screened in a large, population-based cohort from Australia and both single SNP and haplotype analyses were undertaken. RESULTS: Two SNPs were found to be nominally associated with CCT, rs17352842 from FBN1 (p=0.02) and rs3026398 from PAX6 (p=0.02), although neither of these p values survived correction for multiple testing. Haplotype analysis revealed one haplotype within FBN1 (corrected p=0.048) and two haplotypes within PAX6 (strongest corrected p=0.006) associated with CCT. No other SNPs or haplotypes from the remaining genes showed any significant correlation with CCT. CONCLUSIONS: Results from this study suggest that FBN1 and PAX6 are potentially involved in determining CCT. This is the first published study to investigate these genes for association with normal CCT variation. PMID- 20360994 TI - Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with differences in magnitude between center and periphery. AB - PURPOSE: The vertebrate retina develops from the center to the periphery. In amphibians and fish the retinal margin continues to proliferate throughout life, resulting in retinal expansion. This does not happen in mammals. However, some mammalian peripheral retinal pigment epithelial (RPE) cells continue to divide, perhaps as a vestige of this mechanism. The RPE cells are adjacent to the ciliary margin, a known stem cell source. Here we test the hypothesis that peripheral RPE is fundamentally different from central RPE by challenging different regions with microscopic laser burns and charting differential responses in terms of levels of proliferation and the regions over which this proliferation occurs. METHODS: Microscopic RPE lesions were undertaken in rats at different eccentricities and the tissue stained for proliferative markers Ki67 and bromodeoxyuridine (BrdU) and the remodeling metalloproteinase marker 2 (MMP2). RESULTS: All lesions produced local RPE proliferation and tissue remodeling. Significantly more mitosis resulted from peripheral than central lesions. Unexpectedly, single lesions also resulted in RPE cells proliferating across the entire retina. Their number did not increase linearly with lesion number, indicating that they may be a specific population. All lesions repaired and formed apparently normal relations with the neural retina. Repaired RPE was albino. CONCLUSIONS: These results highlight regional RPE differences, revealing an enhanced peripheral repair capacity. Further, all lesions have a marked impact on both local and distant RPE cells, demonstrating a pan retinal signaling mechanism triggering proliferation across the tissue plane. The RPE cells may represent a distinct population as their number did not increase with multiple lesions. The fact that repairing cells were hypopigmented is of interest because reduced pigment is associated with enhanced proliferative capacities in the developing neural retina. PMID- 20360995 TI - Positive Emotional Traits and Ambitious Goals among People at Risk for Mania: The Need for Specificity. AB - Recent psychosocial theories implicate disturbances in reward pursuit among individuals putatively at risk for mania. The present study examined associations of a measure of risk for mania (the Hypomanic Personality Scale; HPS) with both four trait positive emotions (joy, pride, compassion, and love) and ambitious life goals in five domains (fame, wealth, political influence, family, and friends) among 302 participants from two university settings. Findings indicated that higher HPS scores were related to reward (joy) and achievement-focused (pride) positive emotions, with weaker relations to prosocial (compassion, love) positive emotions. HPS scores were more robustly related to extrinsic (fame, politics) as compared to other-oriented (friends, family) ambitious life goals, with the exception of wealth. These effects were independent of current symptoms of mania and depression. Discussion focuses on the implications of elevated reward and achievement-related positive emotions and goals in understanding risk factors for mania. PMID- 20360996 TI - Ruminative Responses to Negative and Positive Affect Among Students Diagnosed with Bipolar Disorder and Major Depressive Disorder. AB - Rumination in response to negative affect has been found to predict the onset, severity, and duration of depressive symptoms. Few researchers, however, have considered rumination within bipolar disorder, nor have studies considered parallel responses that might intensify positive affect. The current study examined self-reported rumination in response to both negative and positive affect among people diagnosed via the SCID with BPD (n = 28), major depressive disorder (MDD; n = 35), or no mood disorder (n = 44). Participants completed the Ruminative Response Scale and the Responses to Positive Affect Questionnaire about their dispositional tendencies. Results indicated that compared to control participants, people with BPD and MDD endorsed heightened rumination in response to negative affect, but only those with BPD endorsed elevated rumination in response to positive affect. Within BPD, ruminative responses to negative affect were explained by depressive symptoms. Goals for understanding responses to negative and positive affect in BPD are suggested. PMID- 20360997 TI - Hexachloroethane: a highly efficient reagent for the synthesis of chlorosilanes from hydrosilanes. AB - A new and efficient chlorination protocol is presented for the preparation of chlorosilanes from hydrosilanes. A variety of chlorinating agents in combination with palladium(II) chloride as the catalyst are examined. Among them, hexachloroethane is found to be the best choice, furnishing the desired product in good to quantitative yields under mild conditions. Various hydrosilanes are used as starting materials to explore the scope of this reaction. PMID- 20360998 TI - Responses to Positive Affect: A Self-Report Measure of Rumination and Dampening. AB - Rumination in response to dysphoric moods has been linked to the onset and maintenance of depressive symptoms; however, responses to positive moods have received less attention despite the theoretical roles of both positive and negative affect in mood disorders. The purpose of the present study was to develop a self-report measure of ruminative and dampening Responses to Positive Affect (RPA), which we called the RPA Questionnaire. In two psychometric studies, the three subscales of the RPA (Dampening, Self-focused positive rumination, and Emotion-focused positive rumination) demonstrated acceptable structural validity, internal consistency, and preliminary evidence of convergent and incremental validity with concurrent measures of self-esteem, depressive rumination, and depressive and manic symptoms among undergraduates. The present results suggest that future research on mood disorders would benefit from measuring responses to both negative and positive moods. PMID- 20361000 TI - Trauma mechanisms and injuries associated with go-karting. AB - Annually, approximately 600 patients seek medical attention after go-kart accidents in the Netherlands. A large variability in injury patterns can be encountered. Knowledge of the trauma mechanisms of go-kart accidents and insight into the associated injuries is limited and requires improvement. Such additional knowledge may lead to customized trauma protocols for patients with a high index of suspicion on go-kart injuries. Research into trauma mechanisms may also lead to implementation of improved or additional safety measures for go-karting, involving both the go-karts itself as well as prerequisites to the go-kart tracks and qualifications for the drivers. The main trauma mechanisms involved in go kart accidents, and three cases to illustrate the variety of injuries are described in the current manuscript. PMID- 20360999 TI - Assessment Tools for Adult Bipolar Disorder. AB - This article reviews the current state of the literature on the assessment of bipolar disorder in adults. Research on reliable and valid measures for bipolar disorder has unfortunately lagged behind assessment research for other disorders, such as major depression. We review diagnostic tools, self-report measures to facilitate screening for bipolar diagnoses, and symptom severity measures. We briefly review other assessment domains, including measures designed to facilitate self-monitoring of symptoms. We highlight particular gaps in the field, including an absence of research on the reliable diagnosis of bipolar II and milder forms of disorder, a lack of empirical data on the best ways to integrate data from multiple domains, and a shortage of measures targeting a broader set of illness-related constructs relevant to bipolar disorder. PMID- 20361001 TI - Measurements of the exerted pressure by pelvic circumferential compression devices. AB - BACKGROUND: Data on the efficacy and safety of non-invasive Pelvic Circumferential Compression Devices (PCCDs) is limited. Tissue damage may occur if a continuous pressure on the skin exceeding 9.3 kPa is sustained for more than two or three hours. The aim of this study was to gain insight into the pressure build-up at the interface, by measuring the PCCD-induced pressure when applying pulling forces to three different PCCDs (Pelvic Binder((R)) , SAM-Sling ((R)) and T-POD((R)) ) in a simplified model. METHODS: The resulting exerted pressures were measured at four 'anatomical' locations (right, left, posterior and anterior) in a model using a pressure measurement system consisting of pressure cuffs. RESULTS: The exerted pressure varied substantially between the locations as well as between the PCCDs. Maximum pressures ranged from 18.9-23.3 kPa and from 19.2 27.5 kPa at the right location and left location, respectively. Pressures at the posterior location stayed below 18 kPa. At the anterior location pressures varied markedly between the different PCCDs. CONCLUSION: The circumferential compression by the different PCCDs showed high pressures measured at the four locations using a simplified model. Difference in design and functional characteristics of the PCCDs resulted in different pressure build-up at the four locations. When following the manufacturer's instructions, the exerted pressure of all three PCCDs tested exceeded the tissue damaging level (9.3 kPa). In case of prolonged use in a clinical situation this might put patients at risk for developing tissue damage. PMID- 20361003 TI - Results of osteochondral autologous transplantation in the knee. AB - Repair of full thickness defects of articular cartilage in the knee is difficult but important to prevent progression to osteoarthritis. The purpose of this retrospective study was to evaluate the clinical results of Osteochondral Autograft Transplant System (OATS) treatment for articular defects of the knee.Between 1999 and 2005, 15 knees (14 patients) were treated by the OATS technique. Age ranged from 27 to 52 years. Cartilage defects were up to 3.75 cm2. The mean follow-up was 42 months. Knee function was assessed by the Lysholmscore and International Knee Documentation Committee (IKDC) Subjective Knee Form. Six patients scored good or excellent. No patient had knee instability. Twelve of 13 patients returned to sports at an intermediate or high level. The subjective assessment score (0-10) changed from 4.7 before operation to 7.2 afterward (P=0.007). The OATS-technique resulted in a decrease in symptoms in patients with localized articular cartilage defects. We consider the OATS technique to be an appropriate treatment for cartilage defects to prevent progression of symptoms. PMID- 20361002 TI - Vascular function and inflammation in rheumatoid arthritis: the role of physical activity. AB - Inflammation disturbs biochemical pathways involved in homeostasis of the endothelium. Research has established clear links between inflammatory mediators, particularly C-reactive protein and tumour necrosis factor alpha, endothelial dysfunction, and atherosclerosis. Endothelial dysfunction and atherosclerosis may be subclinical at early stages, and thus the ability to detect them with non invasive techniques is crucially important, particularly in populations at increased risk for cardiovascular disease, such as those with rheumatoid arthritis. This may allow the identification of interventions that may reverse these processes early on. One of the best non-pharmacological interventions that may achieve this is physical activity. This review explores the associations between inflammation, endothelial dysfunction, and atherosclerosis and discusses the role of exercise in blocking specific pathways in the inflammation, endothelial dysfunction - atherosclerosis network. PMID- 20361004 TI - The perils of do it yourself chemical tattoo removal. PMID- 20361005 TI - AWBAT: early clinical experience. AB - OBJECTIVE: The purpose of this article is to describe the early clinical experience with AWBAT. METHODS: Burn patients requiring (1) donor sites or (2) treatment of a superficial burn wound injury were treated. A total of 45 patients with 69 distinct wounds were included. AWBAT-D was evaluated in donor sites and AWBAT-S was evaluated in superficial partial-thickness burns. Days to healing, pain, hematoma/seroma formation, and infection were noted. Ease of application, adherence, transparency, and physical adaptability details were collected. RESULTS: Average period to healing of donor sites treated with AWBAT-D (n=22 patients with n=26 wounds) was 11.2 days, sigma =1.95, with a range of 8-15 days and a median of 11 days. Pain rating at 24 hours was 1.2, sigma =0.43 (n=18) and at 48 hours mean was 1.2, sigma =0.46 (n=15). Average period to healing of superficial burns treated with AWBAT-S (n=15 patients with n=18 wounds) was 8.1 days, sigma =2.48, with a range of 5-13 days and a median of 7 days. Pain rating at 24 hours was 1.5, sigma =0.85 (n=10) and at 48 hours mean was 1.75, sigma =0.89 (n=8). There was zero incidence of hematoma/seroma. No infections were seen. Results indicate that AWBAT was easily applied with good initial adherence. It was noted to be transparent, conformant, and pliable. DISCUSSION: Early experience demonstrates that AWBAT performs well on donor sites and superficial partial-thickness burns and delivers the desired attributes of a temporary skin substitute including good adherence, infection control, transparency, adapatability, and pain control. PMID- 20361006 TI - Liraglutide in the treatment of type 2 diabetes mellitus: clinical utility and patient perspectives. AB - Type 2 diabetes mellitus (T2DM) is a progressive disease associated with significant morbidity and mortality. There is good evidence that intensive glycemic control reduces the development and progression of complications in patients with diabetes. In order to achieve glycemic targets, patients often require a combination of oral therapy and/or insulin in addition to lifestyle modification. Unfortunately many currently available therapies for T2DM are associated with weight gain and hypoglycemia resulting in poor compliance and subsequent worsening glycemic control. Glucagon like peptide-1 (GLP-1) is an incretin hormone secreted from the small intestine that lowers fasting and postprandial glucose through multiple mechanisms including glucose-dependent insulin secretion, reduction of glucagon secretion, delaying gastric emptying and increased satiety. Liraglutide is a long acting GLP-1 mimetic that is administered once a day by subcutaneous injection and is now licensed for the treatment of T2DM. Phase 3 clinical trials have demonstrated beneficial effects on glycemic control and weight with liraglutide therapy. Within this article, we provide an overview of pharmacology, efficacy, safety and patient experience on liraglutide in the management of T2DM. PMID- 20361007 TI - Phase Behavior of Planar Supported Lipid Membranes Composed of Cholesterol and 1,2-Distearoyl-sn-Glycerol-3-Phosphocholine Examined by Sum-Frequency Vibrational Spectroscopy. AB - The influence of cholesterol (CHO) on the phase behavior of 1,2-distearoyl-sn glycero-3-phosphocholine (DSPC) planar supported lipid bilayers (PSLBs) was investigated by sum-frequency vibrational spectroscopy (SFVS). The intrinsic symmetry constraints of SFVS were exploited to measure the asymmetric distribution of phase segregated phospholipid domains in the proximal and distal layers of DSPC + CHO binary mixtures as a function of CHO content and temperature. The SFVS results suggest that cholesterol significantly affects the phase segregation and domain distribution in PSLBs of DSPC in a concentration dependent manner, similar to that found in bulk suspensions. The SFVS spectroscopic measurements of phase segregation and structure change in the binary mixture indicate that membrane asymmetry must be present in order for the changes in SFVS signal to be observed. These results therefore provide important evidence for the delocalization and segregation of different phase domain structures in PSLBs due to the interaction of cholesterol and phospholipids. PMID- 20361009 TI - Method for Detection of Thiol-containing Amino Acids Using Gold-Polystyrene Composites. AB - This paper reports the preparation of PS-PEI-Au composite colloids via the utilization of a facile method involving poly(ethylenimine) (PEI). The PEI used in the reaction scheme served the role of a linker between Au and PS and additionally as a reducing agent in the conversion of Au ions to Au NPs. The PS PEI-Au colloids thus prepared were characterized by scanning electron microscopy, UV-Vis and IR spectroscopy and cyclic voltammetry. The PS-PEI-Au composites were further used for the detection of the thiol-containing amino acids, cysteine and homocysteine, via Attenuated Total Reflection (ATR) spectroscopy. Experimental results revealed interfacial binding of the amino acids to the composites, and correlated with successive additions of the respective amino acids. PMID- 20361010 TI - Cerebrospinal fluid biomarkers of Alzheimer's disease. AB - Alzheimer's disease will reach epidemic proportions within the next 20-30 years if left unchecked. Currently, there are no treatments that prevent or slow Alzheimer's disease but many are being developed. Parallel efforts to develop biomarkers to aid in disease diagnosis and prognosis, and assess disease risk are currently underway. Clinicopathological and biomarker studies have demonstrated that Alzheimer's disease pathology can be detected preclinically. Using biomarkers to identify affected individuals prior to the onset of clinical symptoms and associated synaptic/neuronal loss should enable novel clinical trial design and early mechanism-based therapeutic intervention. This article summarizes the most promising cerebrospinal fluid biomarkers, highlights novel applications and current challenges, and provides a prediction on how the field may evolve in 5-10 years. PMID- 20361011 TI - Displaced New Orleans Residents in the Aftermath of Hurricane Katrina: Results from a Pilot Survey. AB - This article introduces us to the complexities of conducting social scientific research in a major urban disaster zone and reports on results from the most systematic survey at the time aimed at tracking the whereabouts of pre-Katrina residents during the first year of recovery, the Displaced New Orleans Residents Pilot Survey. This survey drew an area-probability sample of pre-Katrina residents and set out to interview them approximately twelve months after the storm, when educated guesses placed the New Orleans's city population at roughly half its pre-Katrina total. Results confirm that early returnees tended to be disproportionately white, elderly, better educated, and far less likely to have homes rendered uninhabitable by the disaster. These patterns begin to show how demographic processes triggered by the disaster exacerbated existing inequalities in the region, allowing more advantaged residents to return while leaving less advantaged residents dispersed across numerous destinations. PMID- 20361012 TI - A mutation in the FOXE3 gene causes congenital primary aphakia in an autosomal recessive consanguineous Pakistani family. AB - PURPOSE: Aphakia is the complete absence of any lens in the eye, either due to surgical removal of the lens as a result of a perforating wound or ulcer, or due to a congenital anomaly. The purpose of this study was to elucidate the molecular genetics for a large consanguineous Pakistani family with a clear aphakia phenotype. METHODS: The initial homozygosity screening of the family was extended to all the known autosomal recessive cataract loci in order to exclude the possibility of surgical cataract removal leading to aphakia. The screening was performed using polymorphic nucleotide repeat markers, followed by DNA sequencing of a possible candidate gene, the forkhead box protein E3 gene (FOXE3). The identified mutation was counter-checked by a diagnostic restriction enzyme digest of all the family members, and an analysis of the normal population. RESULTS: The initial homozygosity screening of 13 known autosomal recessive loci resulted in negative LOD (logarithm of odds) scores. The aphakia phenotype suggested a mutation in FOXE3 close to the AR-locus 1p34.3-p32.2, and sequence analyses revealed the nonsense mutation c.720C>A, changing cysteine 240 to a stop codon. Segregation in the family was shown by diagnostic restriction enzyme digest, and marker analysis of another aphakia family from Madagascar carrying the same mutation excluded the presence of a founder mutation. Clinical re-examination of the family was not possible due to the escalating security concerns and internal displacement of the population in this region of Pakistan which has prevailed for many months. CONCLUSIONS: FOXE3 is responsible for the early developmental arrest of the lens placode, and the complete loss of a functional FOXE3 protein results in primary aphakia. It can also be deduced that this mutation is quite primitive in origin since the same mutation is responsible for the same phenotypic outcome in two families of geographically different descent. PMID- 20361013 TI - Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. AB - PURPOSE: To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family. METHODS: All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the critical interval, was sequenced bidirectionally. RESULTS: The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts. Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, with a maximum two-point LOD score of 5.21 at theta=0. Sequencing of EPHA2 residing in the critical interval identified a missense mutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T). CONCLUSIONS: Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessive congenital cataracts. PMID- 20361014 TI - Mitochondrial DNA analysis in primary congenital glaucoma. AB - PURPOSE: To screen mitochondrial DNA (mtDNA) for nucleotide variations in primary congenital glaucoma (PCG). METHODS: The entire coding region of the mitochondrial genome was amplified by polymerase chain reaction from 35 PCG patients and 40 controls. The full mtDNA genome except the D-loop was sequenced. All sequences were analyzed against mitochondrial reference sequence NC_012920. RESULTS: MtDNA sequencing revealed a total of 132 and 58 nucleotide variations in PCG and controls, respectively. Of 132 nucleotide variations, 42 (31.81%) were non synonymous and 82 (62.12%) were synonymous changes, and 8 were in RNA genes. The highest number of nucleotide variations were recorded in complex I followed by complex IV, then complex V. Eight patients (22.85%) had potentially pathogenic mtDNA nucleotide changes and twenty (57.14%) had mtDNA sequence changes associated with elevated reactive oxygen species (ROS) production. Mitochondria not only constitute the energy-generating system in the cell, but are also critically involved in calcium signaling and apoptosis. Mitochondrial function can be affected by mutations in mitochondrial and nuclear DNA, chemical insults to components of the electron transport chain, and a lack of substrates such as oxygen. Mitochondrial dysfunction results in an excessive generation of free radicals and reduced mitochondrial respiration. Developing trabecular meshwork (TM) is deficient in antioxidant enzymes, and thus is more susceptible to oxidative stress (OS) induced damage. Previous studies have documented certain mtDNA sequence variations associated with elevated ROS levels and OS. Three such changes (G10398A, A12308G, and G13708A) were present in our patients. Elevated ROS may cause OS. This OS may further damage mtDNA and may cause decreased mitochondrial respiration. This may lead to impaired growth, development and differentiation of TM and consequently trabecular-dysgenesis, which is a characteristic feature of PCG. OS affects both TM and retinal ganglion cells (RGCs) and may be involved in the neuronal death affecting the optic nerve in glaucoma. There are several studies which point to mitochondrial dysfunction in different types of glaucoma and critically participate in RGC death. Recent studies also implicate mitochondrial dysfunction-associated OS as a risk factor for glaucoma patients. It has been reported that elevated hydrostatic pressure causes breakdown of the mitochondrial network by mitochondrial fission and induce cristae depletion and cellular ATP reduction in differentiated RGC-5 cells in vitro as well as in vivo. CONCLUSIONS: A total of 44 novel mtDNA variations were identified in this study. Non-synonymous mtDNA variations may adversely affect respiratory chain, impair OXPHOS pathway result in low ATP production, high ROS production and impair growth, development and differentiation of TM lead to trabecular-dysgenesis and consequently RGC's death. Such cases with mtDNA variations and consequent OS may benefit by early diagnosis and prompt management by antioxidant therapy. This may delay OS induced injury to TM and RGCs and hence improve visual prognosis. PMID- 20361015 TI - A novel mutation in the major intrinsic protein (MIP) associated with autosomal dominant congenital cataracts in a Chinese family. AB - PURPOSE: To detect the underlying genetic defect in a Chinese family affected with bilateral congenital cataracts. METHODS: A detailed family history and clinical data were recorded. Mutation screening was performed in the nuclear cataract-related gene by bidirectional sequencing of the amplified products. The mutation was verified by denaturing high-performance liquid chromatography (DHPLC). RESULTS: Two cataract phenotypes were observed within this family: one eye exhibited Y-suture and nuclear pulverulent opacification of the lens, while the others exhibited complete opacification in the fetal nuclear region. Sequencing of the candidate genes detected a heterozygous c.319G>A change in the coding region of the major intrinsic protein (MIP), resulting in the substitution of a highly conserved Valine by Isoleucine (p.V107I).The mutation was confirmed by DHPLC. CONCLUSIONS: This study has identified a novel MIP mutation, p.V107I in a Chinese family with congenital cataracts. To the best of our knowledge, this is the first reported case of cataracts caused by a mutation in the second extracellular loop domain of MIP. PMID- 20361016 TI - A detailed phenotypic assessment of individuals affected by MFRP-related oculopathy. AB - PURPOSE: To determine the spectrum of mutations and phenotypic variability within patients with mutations in membrane-type frizzled related protein gene (MFRP). METHODS: Individuals were initially ascertained based on a phenotype similar to that previously published in association with MFRP mutations. Affected patients underwent a full ophthalmic examination (best-corrected visual acuity, slit-lamp examination, applanation tonometry, and fundoscopy), color fundus photography, optical coherence tomography, autofluorescence imaging, and electrophysiology. MFRP was identified by a genome-wide scan in the fourth-largest autozygous region in one consanguineous family. Sanger sequencing of all the exons and intron-exon boundaries of MFRP was undertaken in the affected individuals. RESULTS: Seven affected individuals from four families were identified as having mutations in MFRP. Patients from two families were homozygous for mutations already previously described (c.1143_1144 insC and c.492 delC), while those from the other two were compound heterozygous for mutations (c.201G>A and c.491_492 insT, and c.492 delC, and c.1622_1625 delTCTG), three of which were novel. There was considerable phenotypic variability within and among families. Autofluorescence imaging revealed the central macula to be relatively well preserved. Foveal cysts and optic nerve head drusen were present in two of the four families. Electrophysiology results showed rod-cone dystrophy with mild to moderate reduction in macular function in all affected members. CONCLUSIONS: We report three novel MFRP mutations and expand the phenotypic data available on patients with MFRP mutations. PMID- 20361017 TI - Protecting vulnerable road users from injury. PMID- 20361018 TI - A fatal switch for corals? PMID- 20361019 TI - Need-based up-regulation of protein levels in response to deletion of their duplicate genes. AB - Many duplicate genes maintain functional overlap despite divergence over long evolutionary time scales. Deleting one member of a paralogous pair often has no phenotypic effect, unless its paralog is also deleted. It has been suggested that this functional compensation might be mediated by active up-regulation of expression of a gene in response to deletion of its paralog. However, it is not clear how prevalent such paralog responsiveness is, nor whether it is hardwired or dependent on feedback from environmental conditions. Here, we address these questions at the genomic scale using high-throughput flow cytometry of single cell protein levels in differentially labeled cocultures of wild-type and paralog knockout Saccharomyces cerevisiae strains. We find that only a modest fraction of proteins (22 out of 202) show significant up-regulation to deletion of their duplicate genes. However, these paralog-responsive proteins match almost exclusively duplicate pairs whose overlapping function is required for growth. Moreover, media conditions that add or remove requirements for the function of a duplicate gene pair specifically eliminate or create paralog responsiveness. Together, our results suggest that paralog responsiveness in yeast is need-based: it appears only in conditions in which the gene function is required. Physiologically, such need-based responsiveness could provide an adaptive mechanism for compensation of genetic, environmental, or stochastic perturbations in protein abundance. PMID- 20361020 TI - Can animal models of disease reliably inform human studies? AB - H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials. PMID- 20361021 TI - Preventing road deaths--time for data. AB - In this month's editorial, the PLoS Medicine Editors call for better data to support policy changes that could reduce the huge global burden of death and injury from road traffic crashes. PMID- 20361022 TI - Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. AB - The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst "experts" and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such "publication bias" in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach to Meta-analysis and Review of Animal Data in Experimental Studies) database we identified 16 systematic reviews of interventions tested in animal studies of acute ischaemic stroke involving 525 unique publications. Only ten publications (2%) reported no significant effects on infarct volume and only six (1.2%) did not report at least one significant finding. Egger regression and trim and-fill analysis suggested that publication bias was highly prevalent (present in the literature for 16 and ten interventions, respectively) in animal studies modelling stroke. Trim-and-fill analysis suggested that publication bias might account for around one-third of the efficacy reported in systematic reviews, with reported efficacy falling from 31.3% to 23.8% after adjustment for publication bias. We estimate that a further 214 experiments (in addition to the 1,359 identified through rigorous systematic review; non publication rate 14%) have been conducted but not reported. It is probable that publication bias has an important impact in other animal disease models, and more broadly in the life sciences. PMID- 20361023 TI - How microbial community composition regulates coral disease development. AB - Reef coral cover is in rapid decline worldwide, in part due to bleaching (expulsion of photosynthetic symbionts) and outbreaks of infectious disease. One important factor associated with bleaching and in disease transmission is a shift in the composition of the microbial community in the mucus layer surrounding the coral: the resident microbial community-which is critical to the healthy functioning of the coral holobiont-is replaced by pathogenic microbes, often species of Vibrio. In this paper we develop computational models for microbial community dynamics in the mucus layer in order to understand how the surface microbial community responds to changes in environmental conditions, and under what circumstances it becomes vulnerable to overgrowth by pathogens. Some of our model's assumptions and parameter values are based on Vibrio spp. as a model system for other established and emerging coral pathogens. We find that the pattern of interactions in the surface microbial community facilitates the existence of alternate stable states, one dominated by antibiotic-producing beneficial microbes and the other pathogen-dominated. A shift to pathogen dominance under transient stressful conditions, such as a brief warming spell, may persist long after environmental conditions have returned to normal. This prediction is consistent with experimental findings that antibiotic properties of Acropora palmata mucus did not return to normal long after temperatures had fallen. Long-term loss of antibiotic activity eliminates a critical component in coral defense against disease, giving pathogens an extended opportunity to infect and spread within the host, elevating the risk of coral bleaching, disease, and mortality. PMID- 20361024 TI - BMI and risk of serious upper body injury following motor vehicle crashes: concordance of real-world and computer-simulated observations. AB - BACKGROUND: Men tend to have more upper body mass and fat than women, a physical characteristic that may predispose them to severe motor vehicle crash (MVC) injuries, particularly in certain body regions. This study examined MVC-related regional body injury and its association with the presence of driver obesity using both real-world data and computer crash simulation. METHODS AND FINDINGS: Real-world data were from the 2001 to 2005 National Automotive Sampling System Crashworthiness Data System. A total of 10,941 drivers who were aged 18 years or older involved in frontal collision crashes were eligible for the study. Sex specific logistic regression models were developed to analyze the associations between MVC injury and the presence of driver obesity. In order to confirm the findings from real-world data, computer models of obese subjects were constructed and crash simulations were performed. According to real-world data, obese men had a substantially higher risk of injury, especially serious injury, to the upper body regions including head, face, thorax, and spine than normal weight men (all p<0.05). A U-shaped relation was found between body mass index (BMI) and serious injury in the abdominal region for both men and women (p<0.05 for both BMI and BMI(2)). In the high-BMI range, men were more likely to be seriously injured than were women for all body regions except the extremities and abdominal region (all p<0.05 for interaction between BMI and sex). The findings from the computer simulation were generally consistent with the real-world results in the present study. CONCLUSIONS: Obese men endured a much higher risk of injury to upper body regions during MVCs. This higher risk may be attributed to differences in body shape, fat distribution, and center of gravity between obese and normal-weight subjects, and between men and women. Please see later in the article for the Editors' Summary. PMID- 20361025 TI - The silent epidemic of exclusive university licensing policies on compounds for neglected diseases and beyond. PMID- 20361026 TI - Solutions to neglected tropical diseases require vibrant local scientific communities. PMID- 20361027 TI - Pulmonary loiasis and HIV coinfection in rural Cameroon. PMID- 20361028 TI - Rabies in the 21 century. PMID- 20361029 TI - Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. AB - BACKGROUND: The ability to reside and proliferate in macrophages is characteristic of several infectious agents that are of major importance to public health, including the intracellular parasites Trypanosoma cruzi (the etiological agent of Chagas disease) and Leishmania species (etiological agents of Kala-Azar and cutaneous leishmaniasis). Although recent studies have elucidated some of the ways macrophages respond to these pathogens, the relationships between activation programs elicited by these pathogens and the macrophage activation programs elicited by bacterial pathogens and cytokines have not been delineated. METHODOLOGY/PRINCIPAL FINDINGS: To provide a global perspective on the relationships between macrophage activation programs and to understand how certain pathogens circumvent them, we used transcriptional profiling by genome-wide microarray analysis to compare the responses of mouse macrophages following exposure to the intracellular parasites T. cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS), and the cytokines IFNG, TNF, IFNB, IL-4, IL-10, and IL-17. We found that LPS induced a classical activation state that resembled macrophage stimulation by the Th1 cytokines IFNG and TNF. However, infection by the protozoan pathogen L. mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. T. cruzi activated macrophages produced a transcriptional signature characterized by the induction of interferon stimulated genes by 24 h post-infection. Despite this delayed IFN response by T. cruzi, the transcriptional response of macrophages infected by the kinetoplastid pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines. CONCLUSIONS/SIGNIFICANCE: This study provides global gene expression data for a diverse set of biologically significant pathogens and cytokines and identifies the relationships between macrophage activation states induced by these stimuli. By comparing macrophage activation programs to pathogens and cytokines under identical experimental conditions, we provide new insights into how macrophage responses to kinetoplastids correlate with the overall range of macrophage activation states. PMID- 20361030 TI - Nelfinavir, an HIV-1 protease inhibitor, induces oxidative stress-mediated, caspase-independent apoptosis in Leishmania amastigotes. AB - BACKGROUND: Visceral leishmaniasis has now emerged as an important opportunistic disease in patients coinfected with human immunodeficiency virus type-1 (HIV-1). Although the effectiveness of HIV-1 protease inhibitors, such as nelfinavir, in antiretroviral therapies is well documented, little is known of the impact of these drugs on Leishmania in coinfected individuals. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we show that nelfinavir generates oxidative stress in the parasite, leading to altered physiological parameters such as an increase in the sub-G1 DNA content, nuclear DNA fragmentation and loss of mitochondrial potential, which are all characteristics of apoptosis. Pretreatment of axenic amastigotes with the caspase inhibitor z-VAD-fmk did not inhibit the increase in sub-G1 DNA content in nelfinavir-treated parasites, suggesting therefore that this antiviral agent does not kill Leishmania amastigotes in a caspase-dependent manner. Furthermore, we observed that the mitochondrial resident protein endonuclease G is involved. We also demonstrate that parasites overexpressing GSH1 (the rate limiting enzyme of glutathione biosynthesis) were more resistant to nelfinavir when compared to untransfected controls. CONCLUSIONS AND SIGNIFICANCE: These data suggest that nelfinavir induces oxidative stress in Leishmania amastigotes, culminating in caspase-independent apoptosis, in which DNA is degraded by endonuclease G. This study provides a rationale for future, long-term design of new therapeutic strategies to test nelfinavir as a potential antileishmanial agent as well as for possible future use in Leishmania/HIV-1 coinfections. PMID- 20361032 TI - First description of a cluster of acute/subacute paracoccidioidomycosis cases and its association with a climatic anomaly. AB - BACKGROUND: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in Sao Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 ( approximately 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal ( approximately 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Nino event, the strongest in the last 50 years. CONCLUSIONS/SIGNIFICANCE: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Nino Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures. PMID- 20361031 TI - Prevalence and correlates of helminth co-infection in Kenyan HIV-1 infected adults. AB - BACKGROUND: Deworming HIV-1 infected individuals may delay HIV-1 disease progression. It is important to determine the prevalence and correlates of HIV 1/helminth co-infection in helminth-endemic areas. METHODS: HIV-1 infected individuals (CD4>250 cells/ul) were screened for helminth infection at ten sites in Kenya. Prevalence and correlates of helminth infection were determined. A subset of individuals with soil-transmitted helminth infection was re-evaluated 12 weeks following albendazole therapy. RESULTS: Of 1,541 HIV-1 seropositive individuals screened, 298 (19.3%) had detectable helminth infections. Among individuals with helminth infection, hookworm species were the most prevalent (56.3%), followed by Ascaris lumbricoides (17.1%), Trichuris trichiura (8.7%), Schistosoma mansoni (7.1%), and Strongyloides stercoralis (1.3%). Infection with multiple species occurred in 9.4% of infections. After CD4 count was controlled for, rural residence (RR 1.40, 95% CI: 1.08-1.81), having no education (RR 1.57, 95% CI: 1.07-2.30), and higher CD4 count (RR 1.36, 95% CI: 1.07-1.73) remained independently associated with risk of helminth infection. Twelve weeks following treatment with albendazole, 32% of helminth-infected individuals had detectable helminths on examination. Residence, education, and CD4 count were not associated with persistent helminth infection. CONCLUSIONS: Among HIV-1 seropositive adults with CD4 counts above 250 cells/mm(3) in Kenya, traditional risk factors for helminth infection, including rural residence and lack of education, were associated with co-infection, while lower CD4 counts were not. PMID- 20361033 TI - Effects of Detergents on Activity, Thermostability and Aggregation of Two Alkalithermophilic Lipases from Thermosyntropha lipolytica. AB - Thermosyntropha lipolytica DSM 11003, an anaerobic thermophilic lipolytic bacterium, produces the two alkalithermophilic lipases, LipA and LipB. Among all tested detergents, the two lipases were mostly affected by SDS when used at concentrations below its critical micelle concentration (CMC). In the absence of SDS, the v(max) of both LipA and LipB were 12.6 U.mg(-1) and 13.3 U.mg(-1) and K(0.5) were 1.8 mM and 1.65 mM, respectively at 96 degrees C and pH(opt) (25 masculineC)of 9.4-9.6. In the presence of 0.2% SDS, the v(max) increased to 105 U.mg(-1) and 112 U.mg(-1), and K(0.5) values decreased to 200 microM and 140 microM for LipA and LipB, respectively. Inhibitory assays of lipases using diisopropyl p-nitrophenylphosphate (E600) with increasing concentration of SDS and Tween 20 strongly suggest that SDS and Tween 20 do bind to the lid domain and/or active site pocket, thus promoting conformational changes that facilitate active site accessibility for the substrate. The two lipases exhibited moderate activation in the presence of nonionic detergents when used below their CMC values. Both lipases were found to exhibit strong tendency to aggregate as observed through gel filtration chromatography and gradient native gel electrophoresis. The addition of 1.0% (w/v) SDS led to disaggregation as the lipases were eluted corresponding to their monomeric mass (based on SDS gel electrophoresis value) and caused a significant decrease in thermostability, suggesting that, enzyme aggregation might be a major contributor to the high thermostability of LipA and LipB. PMID- 20361034 TI - One-Day vs Two-Day Epidural Analgesia for Total Knee Arthroplasty (TKA): A Retrospective Cohort Study. AB - INTRODUCTION: Over 500,000 total knee arthroplasties (TKAs) are performed annually in the US, yet postoperative pain management varies widely. In patients managed with epidural analgesia, the epidural catheter is generally removed on the second postoperative day. We compared in-hospital outcomes associated with removing the epidural catheter on postoperative day 1 (POD1-group) vs on postoperative day 2 (POD2-group) among patients undergoing TKA. METHODS: We identified 89 patients who had TKA performed by a single surgeon from January through July 2007, and who were managed with epidural analgesia. This study took advantage of a change of policy from removing the epidural on the second postoperative day prior to March 2007 (n = 34) to removing the epidural on the first postoperative day thereafter (n = 55). Data were obtained by medical record review and analyzed with bivariate and multivariate techniques. Outcomes included knee range of motion (ROM), pain (0-10 scale), distance walked, narcotic usage, and length of stay. RESULTS: The mean patient age was 68 +/- 10 years. We did not identify clinically important differences in preoperative characteristics across groups. Patients in the POD1- group had a shorter length of stay (median of 3 vs 4 days in the POD2-group, p<0.001). The POD1-group also walked a greater distance on the second postoperative day (mean of 38 feet vs 9 feet in the POD2-group, p < 0.002). We did not observe a difference between the two groups with respect to change in passive ROM, pain on the second postoperative day, or narcotic usage. The POD1-group had more restricted continuous passive motion settings on the second postoperative day than the POD2-group (50 degrees vs 65 degrees , p = 0.031), and the POD1-group had somewhat worse passive range of motion at discharge (e.g. passive flexion 82o vs 76o in the POD2- group, p = 0.078). CONCLUSION: The balance between a shorter hospital stay and earlier walking achievement with the POD1-strategy-- vs better ROM at the time of discharge with the POD2-strategy-- should be considered when planning TKA pain management. These results should be confirmed with longer term studies and randomized designs. EVIDENCE LEVEL III: Retrospective comparative study. PMID- 20361035 TI - Complex and unstable simple elbow dislocations: a review and quantitative analysis of individual patient data. AB - OBJECTIVE: The primary objective of this review of the literature with quantitative analysis of individual patient data was to identify the results of available treatments for complex elbow dislocations and unstable simple elbow dislocations. The secondary objective was to compare the results of patients with complex elbow dislocations and unstable elbow joints after repositioning of simple elbow dislocations, which were treated with an external fixator versus without an external fixator. SEARCH STRATEGY: Electronic databases MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials. SELECTION CRITERIA: Studies were eligible for inclusion if they included individual patient data of patients with complex elbow dislocations and unstable simple elbow dislocations. DATA ANALYSIS: The different outcome measures (MEPI, Broberg and Morrey, ASES, DASH, ROM, arthritis grading) are presented with mean and confidence intervals. MAIN RESULTS: The outcome measures show an acceptable range of motion with good functional scores of the different questionnaires and a low mean arthritis score. Thus, treatment of complex elbow dislocations with ORIF led to a moderate to good result. Treatment of unstable simple elbow dislocations with repair of the collateral ligaments with or without the combination of an external fixator is also a good option. The physician-rated (MEPI, Broberg and Morrey), patient-rated (DASH) and physician- and patient-rated (ASES) questionnaires showed good intercorrelations. Arthritis classification by x-ray is only fairly correlated with range of motion. Elbow dislocations are mainly on the non-dominant side. PMID- 20361036 TI - Gene-gene interactions lead to higher risk for development of type 2 diabetes in an Ashkenazi Jewish population. AB - BACKGROUND: Evidence has accumulated that multiple genetic and environmental factors play important roles in determining susceptibility to type 2 diabetes (T2D). Although variants from candidate genes have become prime targets for genetic analysis, few studies have considered their interplay. Our goal was to evaluate interactions among SNPs within genes frequently identified as associated with T2D. METHODS/PRINCIPAL FINDINGS: Logistic regression was used to study interactions among 4 SNPs, one each from HNF4A[rs1884613], TCF7L2[rs12255372], WFS1[rs10010131], and KCNJ11[rs5219] in a case-control Ashkenazi sample of 974 diabetic subjects and 896 controls. Nonparametric multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) were used to confirm findings from the logistic regression analysis. HNF4A and WFS1 SNPs were associated with T2D in logistic regression analyses [P<0.0001, P<0.0002, respectively]. Interaction between these SNPs were also strong using parametric or nonparametric methods: the unadjusted odds of being affected with T2D was 3 times greater in subjects with the HNF4A and WFS1 risk alleles than those without either (95% CI = [1.7 5.3]; P7 million mononucleosome positions and >7 million dinucleosome positions. We showed that the distributions of the lengths of the mononucleosomal DNA fragments after 15 min and 30-min treatments with micrococcal nuclease (MNase) showed a single peak at 168 nt and 160 nt, respectively. The distributions of the lengths of the dinucleosomal DNA fragments after 15-min- and 30-min-treatment with MNase showed a single peak at 321 nt and 306 nt, respectively. The nucleosomal DNA fragments obtained from the TSA-treated cells were significantly longer than those obtained from the untreated cells. On the other hand, most of the genes did not undergo any change after treatment. Between the TSA-treated and untreated cells, only 77 genes had >or=2-fold change in expression levels. In addition, our results showed that the locations where mononucleosomes were frequently detected were conserved between the TSA-treated cells and untreated cells in the gene promoters (lower density of the nucleosomes). However, these locations were less conserved in the bodies (higher density of the nucleosomes) of genes with >or=2-fold changes. Our findings indicate that TSA influences the nucleosome positions, especially of the regions with high density of the nucleosomes by elongation of the nucleosomal DNA. However, most of the nucleosome positions are conserved in the gene promoters, even after treatment with TSA, because of the low density of nucleosomes in the gene promoters. PMID- 20361044 TI - Human population differentiation is strongly correlated with local recombination rate. AB - Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental F(ST) shows negative correlation with recombination rate, with F(ST) reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P<<10(-12)). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and F(ST) has a qualitatively different relationship for F(ST) between African and non-African populations and for F(ST) between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history. PMID- 20361045 TI - Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase. AB - Frequent activation of the AKT serine-threonine kinase in cancer confers resistance to therapy. AKT is activated by a multi-step process involving phosphatidylinositide (PtdIns) phosphate-mediated recruitment of AKT and its upstream kinases, including 3-Phosphoinositide-dependent kinase 1 (PDK1), to the inner surface of the cell membrane. PDK1 in the appropriate context phosphorylates AKT at threonine 308 (T308) to activate AKT. Whether PtdIns(3,4,5)Ps (PtdInsP3) binding and AKT membrane translocation mediate functions other than formation of a functional PDK1::AKT complex have not been fully elucidated. We fused complementary fragments of intensely fluorescent protein (IFP) to AKT1 and PDK1 to induce a stable complex to study the prerequisites of AKT1 phosphorylation and function. In the stabilized PDK1 IFPC::IFPN-AKT1 complex, AKT1 T308 phosphorylation was independent of PtdIns, as demonstrated by treatment with Phosphatidylinositol 3 Kinase (PI3K) inhibitors. Further when interaction with PtdIns and the cell membrane was prevented by creating PH-domain mutants of AKT1 (R25A) and PDK1 (R474A), AKT1 phosphorylation on T308 was maintained in the PDK1-IFPC::IFPN-AKT1 complex. The PDK1-IFPC::IFPN AKT1 complex was sufficient for phosphorylation of known AKT substrates, and conferred resistance to inhibitors of PI3K (LY294002, PI103, GDC0941 and TGX286) but not inhibitors of the downstream TORC1 complex (rapamycin). Thus the locus of action of targeted therapeutics can be elucidated by the constitutively active AKT1 complex. Our data indicate that PtdIns and membrane localization are not required for AKT phosphorylation and activation, but rather serve to induce a functional physical interaction between PDK1 and AKT. The PDK1-IFPC::IFPN-AKT1 complex provides a cell-based platform to examine specificity of drugs targeting PI3K pathway components. PMID- 20361046 TI - Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia. AB - Adenovirus is an important respiratory pathogen. Adenovirus fiber from most serotypes co-opts the Coxsackie-Adenovirus Receptor (CAR) to bind and enter cells. However, CAR is a cell adhesion molecule localized on the basolateral membrane of polarized epithelia. Separation from the lumen of the airways by tight junctions renders airway epithelia resistant to inhaled adenovirus infection. Although a role for CAR in viral spread and egress has been established, the mechanism of initial respiratory infection remains controversial. CAR exists in several protein isoforms including two transmembrane isoforms that differ only at the carboxy-terminus (CAR(Ex7) and CAR(Ex8)). We found low-level expression of the CAR(Ex8) isoform in well-differentiated human airway epithelia. Surprisingly, in contrast to CAR(Ex7), CAR(Ex8) localizes to the apical membrane of epithelia where it augments adenovirus infection. Interestingly, despite sharing a similar class of PDZ-binding domain with CAR(Ex7), CAR(Ex8) differentially interacts with PICK1, PSD-95, and MAGI-1b. MAGI 1b appears to stoichiometrically regulate the degradation of CAR(Ex8) providing a potential mechanism for the apical localization of CAR(Ex8) in airway epithelial. In summary, apical localization of CAR(Ex8) may be responsible for initiation of respiratory adenoviral infections and this localization appears to be regulated by interactions with PDZ-domain containing proteins. PMID- 20361047 TI - Drug-class specific impact of antivirals on the reproductive capacity of HIV. AB - Predictive markers linking drug efficacy to clinical outcome are a key component in the drug discovery and development process. In HIV infection, two different measures, viral load decay and phenotypic assays, are used to assess drug efficacy in vivo and in vitro. For the newly introduced class of integrase inhibitors, a huge discrepancy between these two measures of efficacy was observed. Hence, a thorough understanding of the relation between these two measures of drug efficacy is imperative for guiding future drug discovery and development activities in HIV. In this article, we developed a novel viral dynamics model, which allows for a mechanistic integration of the mode of action of all approved drugs and drugs in late clinical trials. Subsequently, we established a link between in vivo and in vitro measures of drug efficacy, and extract important determinants of drug efficacy in vivo. The analysis is based on a new quantity-the reproductive capacity-that represents in mathematical terms the in vivo analog of the read-out of a phenotypic assay. Our results suggest a drug-class specific impact of antivirals on the total amount of viral replication. Moreover, we showed that the (drug-)target half life, dominated by immune-system related clearance processes, is a key characteristic that affects both the emergence of resistance as well as the in vitro-in vivo correlation of efficacy measures in HIV treatment. We found that protease- and maturation inhibitors, due to their target half-life, decrease the total amount of viral replication and the emergence of resistance most efficiently. PMID- 20361048 TI - The impact of contact tracing in clustered populations. AB - The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard "mass action" models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease. PMID- 20361049 TI - Investigating homology between proteins using energetic profiles. AB - Accumulated experimental observations demonstrate that protein stability is often preserved upon conservative point mutation. In contrast, less is known about the effects of large sequence or structure changes on the stability of a particular fold. Almost completely unknown is the degree to which stability of different regions of a protein is generally preserved throughout evolution. In this work, these questions are addressed through thermodynamic analysis of a large representative sample of protein fold space based on remote, yet accepted, homology. More than 3,000 proteins were computationally analyzed using the structural-thermodynamic algorithm COREX/BEST. Estimated position-specific stability (i.e., local Gibbs free energy of folding) and its component enthalpy and entropy were quantitatively compared between all proteins in the sample according to all-vs.-all pairwise structural alignment. It was discovered that the local stabilities of homologous pairs were significantly more correlated than those of non-homologous pairs, indicating that local stability was indeed generally conserved throughout evolution. However, the position-specific enthalpy and entropy underlying stability were less correlated, suggesting that the overall regional stability of a protein was more important than the thermodynamic mechanism utilized to achieve that stability. Finally, two different types of statistically exceptional evolutionary structure-thermodynamic relationships were noted. First, many homologous proteins contained regions of similar thermodynamics despite localized structure change, suggesting a thermodynamic mechanism enabling evolutionary fold change. Second, some homologous proteins with extremely similar structures nonetheless exhibited different local stabilities, a phenomenon previously observed experimentally in this laboratory. These two observations, in conjunction with the principal conclusion that homologous proteins generally conserved local stability, may provide guidance for a future thermodynamically informed classification of protein homology. PMID- 20361050 TI - Temperature control of fimbriation circuit switch in uropathogenic Escherichia coli: quantitative analysis via automated model abstraction. AB - Uropathogenic Escherichia coli (UPEC) represent the predominant cause of urinary tract infections (UTIs). A key UPEC molecular virulence mechanism is type 1 fimbriae, whose expression is controlled by the orientation of an invertible chromosomal DNA element-the fim switch. Temperature has been shown to act as a major regulator of fim switching behavior and is overall an important indicator as well as functional feature of many urologic diseases, including UPEC host pathogen interaction dynamics. Given this panoptic physiological role of temperature during UTI progression and notable empirical challenges to its direct in vivo studies, in silico modeling of corresponding biochemical and biophysical mechanisms essential to UPEC pathogenicity may significantly aid our understanding of the underlying disease processes. However, rigorous computational analysis of biological systems, such as fim switch temperature control circuit, has hereto presented a notoriously demanding problem due to both the substantial complexity of the gene regulatory networks involved as well as their often characteristically discrete and stochastic dynamics. To address these issues, we have developed an approach that enables automated multiscale abstraction of biological system descriptions based on reaction kinetics. Implemented as a computational tool, this method has allowed us to efficiently analyze the modular organization and behavior of the E. coli fimbriation switch circuit at different temperature settings, thus facilitating new insights into this mode of UPEC molecular virulence regulation. In particular, our results suggest that, with respect to its role in shutting down fimbriae expression, the primary function of FimB recombinase may be to effect a controlled down regulation (rather than increase) of the ON-to-OFF fim switching rate via temperature-dependent suppression of competing dynamics mediated by recombinase FimE. Our computational analysis further implies that this down-regulation mechanism could be particularly significant inside the host environment, thus potentially contributing further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs. PMID- 20361052 TI - All mold is not alike: the importance of intraspecific diversity in necrotrophic plant pathogens. PMID- 20361051 TI - Exoerythrocytic Plasmodium parasites secrete a cysteine protease inhibitor involved in sporozoite invasion and capable of blocking cell death of host hepatocytes. AB - Plasmodium parasites must control cysteine protease activity that is critical for hepatocyte invasion by sporozoites, liver stage development, host cell survival and merozoite liberation. Here we show that exoerythrocytic P. berghei parasites express a potent cysteine protease inhibitor (PbICP, P. berghei inhibitor of cysteine proteases). We provide evidence that it has an important function in sporozoite invasion and is capable of blocking hepatocyte cell death. Pre incubation with specific anti-PbICP antiserum significantly decreased the ability of sporozoites to infect hepatocytes and expression of PbICP in mammalian cells protects them against peroxide- and camptothecin-induced cell death. PbICP is secreted by sporozoites prior to and after hepatocyte invasion, localizes to the parasitophorous vacuole as well as to the parasite cytoplasm in the schizont stage and is released into the host cell cytoplasm at the end of the liver stage. Like its homolog falstatin/PfICP in P. falciparum, PbICP consists of a classical N-terminal signal peptide, a long N-terminal extension region and a chagasin-like C-terminal domain. In exoerythrocytic parasites, PbICP is posttranslationally processed, leading to liberation of the C-terminal chagasin-like domain. Biochemical analysis has revealed that both full-length PbICP and the truncated C terminal domain are very potent inhibitors of cathepsin L-like host and parasite cysteine proteases. The results presented in this study suggest that the inhibitor plays an important role in sporozoite invasion of host cells and in parasite survival during liver stage development by inhibiting host cell proteases involved in programmed cell death. PMID- 20361053 TI - Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis. AB - Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect. PMID- 20361055 TI - Expansion, maintenance, and memory in NK and T cells during viral infections: responding to pressures for defense and regulation. PMID- 20361054 TI - Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia. AB - Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection. PMID- 20361056 TI - Transgenic rat model of neurodegeneration caused by mutation in the TDP gene. AB - TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43 related neurodegenerative diseases. PMID- 20361057 TI - Initial genomics of the human nucleolus. AB - We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs) in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NAD-localized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NAD-specific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture. PMID- 20361058 TI - Local-scale patterns of genetic variability, outcrossing, and spatial structure in natural stands of Arabidopsis thaliana. AB - As Arabidopsis thaliana is increasingly employed in evolutionary and ecological studies, it is essential to understand patterns of natural genetic variation and the forces that shape them. Previous work focusing mostly on global and regional scales has demonstrated the importance of historical events such as long-distance migration and colonization. Far less is known about the role of contemporary factors or environmental heterogeneity in generating diversity patterns at local scales. We sampled 1,005 individuals from 77 closely spaced stands in diverse settings around Tubingen, Germany. A set of 436 SNP markers was used to characterize genome-wide patterns of relatedness and recombination. Neighboring genotypes often shared mosaic blocks of alternating marker identity and divergence. We detected recent outcrossing as well as stretches of residual heterozygosity in largely homozygous recombinants. As has been observed for several other selfing species, there was considerable heterogeneity among sites in diversity and outcrossing, with rural stands exhibiting greater diversity and heterozygosity than urban stands. Fine-scale spatial structure was evident as well. Within stands, spatial structure correlated negatively with observed heterozygosity, suggesting that the high homozygosity of natural A. thaliana may be partially attributable to nearest-neighbor mating of related individuals. The large number of markers and extensive local sampling employed here afforded unusual power to characterize local genetic patterns. Contemporary processes such as ongoing outcrossing play an important role in determining distribution of genetic diversity at this scale. Local "outcrossing hotspots" appear to reshuffle genetic information at surprising rates, while other stands contribute comparatively little. Our findings have important implications for sampling and interpreting diversity among A. thaliana accessions. PMID- 20361059 TI - Role of extended release quetiapine in the management of bipolar disorders. AB - Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA) bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder. PMID- 20361060 TI - Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. AB - About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence. PMID- 20361061 TI - Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole. AB - Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient's previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson's disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence. PMID- 20361062 TI - Post-traumatic stress in patients with injury-related chronic pain participating in a multimodal pain rehabilitation program. AB - AIM: To investigate post-traumatic stress, pain intensity, depression, and anxiety in patients with injury-related chronic pain before and after participating in multimodal pain rehabilitation. METHODS: Twenty-eight patients, 21 women and seven men, who participated in the multimodal rehabilitation programs (special whiplash program for whiplash injuries within 1.5 years after the trauma or ordinary program) answered a set of questionnaires to assess post traumatic stress (Impact of Event Scale [IES], pain intensity [Visual Analogue Scale (VAS)], depression, and anxiety (Hospital Anxiety and Depression Scale [HAD] before and after the programs. RESULTS: Both pain intensity and post traumatic stress decreased significantly after the rehabilitation programs in comparison with before (VAS: 57.8 +/- 21.6 vs. 67.5 +/- 21.9; P = 0.009, IES total score 21.8 +/- 13.2 vs. 29.5 +/- 12.9; P < 0.001). Patients younger than 40 years reported a statistically higher level of post-traumatic stress compared with patients older than 40 years both before (P = 0.037) and after rehabilitation (P = 0.023). No statistically significant differences were found on the HAD scores. CONCLUSION: The multimodal rehabilitation programs were effective in reducing both pain intensity and post-traumatic stress. The experience of higher levels of post-traumatic stress in younger persons has to be taken into account when managing patients with injury-related chronic pain. PMID- 20361063 TI - Ego mechanisms of defense are associated with patients' preference of treatment modality independent of psychological distress in end-stage renal disease. AB - Several parameters mediate the selection of treatment modality in end-stage renal disease (ESRD). The nephrology community suggests that patient preference should be the prime determinant of modality choice. We aimed to test whether ego mechanisms of defense are associated with patients' treatment modality preferences, independent of psychological distress. In 58 eligible ESRD patients who had themselves chosen their treatment modality, we administered the Symptom Distress Checklist-90-R and the Defense Style Questionnaire. Thirty-seven patients (53.4%) had chosen hemodialysis and 21 (46.6%) peritoneal dialysis. Patients who preferred peritoneal dialysis were younger (odds ratio [OR], 0.89; 95% confidence interval [CI]: 0.804-0.988), had received more education (OR, 8.84; 95% CI: 1.301-60.161), and were twice as likely to adopt an adaptive defense style as compared to patients who preferred hemodialysis (57.1% vs 27.0%, respectively; P < 0.033). On the contrary, the latter were more likely to adopt an image-distorting defense style (35.1% vs 14.3%; P = 0.038) and passive aggressive defenses (OR, 0.73: 95% CI: 0.504-1.006). These results were independent of psychological distress. Our findings indicate that the patient's personality should be taken into account, if we are to better define which modalities are best suited to which patients. Also, physicians should bear in mind passive-aggressive behaviors that warrant attention and intervention in patients who preferred hemodialysis. PMID- 20361064 TI - A factor analytic study of the Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF). AB - OBJECTIVES: The Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF) is a specific questionnaire measuring health-related quality of life for human immunodeficiency virus-infected people in the era of highly active antiretroviral therapy. The main goal of this study was to examine the construct validity of this questionnaire by confirmation of its hypothesized dimensional structure. METHODS: Baseline quality of life data from four clinical studies were collected and a confirmatory factor analysis of the ISSQoL-CEF items was carried out. Both first-order and second-order factor models were tested: Model 1 with nine correlated first-order factors; Model 2 with three correlated second-order factors (Physical, Mental, and Social Health); Model 3 with two correlated second-order factors (Physical and Mental/Social Health); Model 4 with only one second-order factor (General Health). RESULTS: A total of 261 patients were surveyed. Model 1 had a good fit to the data. Model 2 had an acceptable fit to the data and it was the best of all hierarchical models. However, Model 2 fitted the data worse than Model 1. CONCLUSIONS: The findings of in this study, consistent with the results of previous study, pointed out the construct validity of the ISSQoL-CEF. PMID- 20361066 TI - Novel radiotherapy schedules aid recovery of normal tissues after treatment. PMID- 20361065 TI - Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism. AB - Warfarin therapy reduces morbidity and mortality related to thromboembolism. Yet adherence to long-term warfarin therapy remains challenging due to the risks of anticoagulant-associated complications and the burden of monitoring. The aim of this paper is to review determinants of adherence and persistence on long-term anticoagulant therapy for atrial fibrillation and venous thromboembolism. We evaluate what the current literature reveals about the impact of warfarin on quality of life, examine warfarin trial data for patterns of adherence, and summarize known risk factors for warfarin discontinuation. Studies suggest only modest adverse effects of warfarin on quality of life, but highlight the variability of individual lifestyle experiences of patients on warfarin. Interestingly, clinical trials comparing anticoagulant adherence to alternatives (such as aspirin) show that discontinuation rates on warfarin are not consistently higher than in control arms. Observational studies link a number of risk factors to warfarin non-adherence including younger age, male sex, lower stroke risk, poor cognitive function, poverty, and higher educational attainment. In addition to differentiating the relative impact of warfarin-associated complications (such as bleeding) versus the lifestyle burdens of warfarin monitoring on adherence, future investigation should focus on optimizing patient education and enhancing models of physician-patient shared-decision making around anticoagulation. PMID- 20361067 TI - Small bowel tumors and videocapsule: a productive union. PMID- 20361068 TI - How toxic is amiodarone to the liver? PMID- 20361069 TI - A preliminary investigation of exhaled breath from patients with celiac disease using selected ion flow tube mass spectrometry. AB - BACKGROUND AND AIMS: Breath diagnostics, the measurement of volatile chemicals in human breath, is currently receiving attention as a technique for the detection of disease which, being non-invasive in nature, is particularly suited to screening for pre-symptomatic disease in healthy populations. A disorder in which more effective screening would be beneficial is celiac disease (CD), an under diagnosed autoimmune disease of the small intestine characterized by nutritional malabsorption, which presents with diverse, and sometimes serious, symptoms. We aimed to determine whether breath analyses could be used to screen for the presence of CD. METHODS: Based on our hypotheses that malabsorption of dietary carbohydrates would lead to over production of alcohol fermentation products in the large intestine, we investigated levels of alcohols in the breath of 10 patients with CD compared to that in 10 healthy controls using selected ion flow tube mass spectrometry (SIFT-MS). RESULTS: No differences were found in the breath levels of methanol, propanol, butanol, heptanol or hexanol investigated using chemical ionization of breath air with H3O+ and/or NO+ precursor ions. In one patient, diagnosed within days of our study and not currently in receipt of any therapeutic intervention, a relatively high production of three product ions was detected compared to all other study patients. CONCLUSION: Our data suggest that breath alcohol levels are unlikely to be of diagnostic use in CD, although further investigation of those recently diagnosed with the disorder may be warranted. PMID- 20361070 TI - Small bowel tumors in patients undergoing capsule endoscopy: a single center experience. AB - BACKGROUND AND AIMS: Small bowel tumors (SBTs) are rare, accounting for 1-3% of all gastrointestinal malignancies. Since the introduction of capsule endoscopy (CE), several studies have suggested that their frequency may be substantially higher. The present study is aimed at evaluating the prevalence, clinical presentation, laboratory parameters, endoscopic appearance, and diagnostic work up of SBTs in patients undergoing CE in a single referral center. PATIENTS AND METHODS: During 2003-2009, 102 patients underwent CE. For each patient with lesions suggesting SBT at CE, with subsequent diagnostic/ therapeutic work-up leading to histological confirmation, we registered: clinical presentation, hemoglobin level, small bowel follow-through, red blood cells scintigraphy, CT enterography, enteroscopy, histological confirmation and management. RESULTS: SBTs were detected in 5 patients (mean age 55.2+/-15.8 years) of 102 undergoing CE (4.9%). The main indication for CE was obscure gastrointestinal bleeding, occult or overt. All patients had undergone, before CE, at least one procedure evaluating the small bowel after negative upper endoscopy and colonoscopy. All patients had iron-deficiency anemia, three had abdominal pain, two had episodes of nausea /vomiting and one had diarrhoea and abdominal distension. The main SBT type was gastrointestinal stromal tumor. After CE, 3 patients underwent single balloon enteroscopy; surgery was performed in all patients. Mean follow-up time was 19+/-17 (range 2-36) months; one patient died during follow-up. No retention of capsule occurred. CONCLUSIONS: CE could be used as first choice for diagnostic investigation in patients suspected to have SBTs. PMID- 20361071 TI - Colonoscopy and sedation in Romania: early experience using a balanced propofol regimen. AB - The aim of this study was to evaluate if the sedation during colonoscopy is correctly performed in our patients, especially because it is usually performed by residents in anesthesiology. METHODS: we retrospectively evaluated sedation in all the colonoscopies performed in our Endoscopy Department in 2007, by analyzing the sedation scheme that was used. RESULTS: 974 colonoscopies were evaluated. The following sedation schemes were used in the majority of cases: midazolam+propofol+fentanyl-507 patients (52.1%) and diazepam+propofol+fentanyl 258 patients (26.5%). Propofol (in combination with one or more other agents) was used for sedation in 96.9% of cases. The mean doses of drugs were: propofol 125.2+/-67.7 mg, midazolam 2.29+/-0.84 mg (or diazepam 3.4+/-1.4 mg) and fentanyl 59+/-10 microg. The following complications were observed during sedation for colonoscopy: 6 patients (0.6%) developed hypoxemia, which was managed successfully with supplemental oxygen administration or flumazenil injection; 1 patient (0.1%) suffered a cardiac arrest that was successfully managed. There were no deaths or other complications. CONCLUSIONS: Propofol, combined with an opioid and a benzodiazepine, was used in approximately 97% of cases. The rate of significant oxygen desaturation was low (0.6%). No fatal complications occurred. The mean doses of propofol used were higher than those from published data, while the doses of midazolam and fentanyl were similar. PMID- 20361072 TI - Probiotics in diverticular disease of the colon: an open label study. AB - AIM: To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. METHODS: Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). RESULTS: Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (p<0.01 vs baseline values). The microbiological study showed that, as compared to baseline values, SCM-III enabled a significant increase of the lactobacilli and bifidobacteria counting and a trend decrease of clostridia. Genomic analysis confirmed the survivability of the ingested strain as long as treatment was given. CONCLUSIONS: The present symbiotic mixture seems to be effective in preventing recurrence of symptomatic uncomplicated diverticular disease of the colon, especially in those patients with constipation-predominant features. PMID- 20361073 TI - Diabetes is not an independent predictor of gastroparesis in symptomatic patients referred for gastric emptying studies. AB - BACKGROUND: It is commonly presumed that diabetics are more prone to gastroparesis when compared to non-diabetics. OBJECTIVE: To ascertain whether diabetes is an independent predictor of gastroparesis in symptomatic patients who are referred for gastric emptying studies. METHODS: This was a cross sectional observational study. The study cohort consisted of 172 consecutive patients who had been referred for gastric emptying studies. Seventy-four of the 172 patients had evidence of diabetes. RESULTS: Gastroparesis was diagnosed in 93 of the 172 patients (54%). Multiple logistic regression analysis did not reveal diabetes to be an independent risk factor (OR 0.77, CI 0.37-1.56, p=0.46). But age>50 years was a significant predictor (OR 3.43, CI 1.62-7.23, p=0.001). The sex of the patient was not a contributing variable (OR 1.47, CI 0.72-2.98, p=0.28). CONCLUSION: Diabetes is not an independent predictor of gastroparesis in patients with gastrointestinal symptoms referred for gastric emptying studies. Age over 50 years was a significant predictor. PMID- 20361074 TI - A cross-sectional epidemiological study of HBV, HCV, HDV and HEV prevalence in the SubCarpathian and South-Eastern regions of Romania. AB - AIM: To evaluate the prevalence of HBV, HCV, HDV and HEV infections in populations with different categories of risk and the seroprevalence of HBV and HCV infections in subjects asking for a medical examination. METHOD: We conducted a cross-sectional, epidemiological study in 2,851 subjects from the SubCarpathian and South-Eastern Romania (including 17 counties, 34% of the country area and 42% of the population). The subjects were divided into four groups: controls (n=2,540, i.e. consecutive subjects asking for a medical examination), subjects with very low risk (students; n=44), with low risk (doctors and nurses; n=93) and with high risk for viral hepatitis (hemodialysis patients; n=174). All subjects were screened for HBsAg, antiHCV and ALT level. In populations at risk, antiHBs, HBeAg, antiHBe, antiHBc (IgG), HBV-DNA, HCV-RNA, antiHDV(IgG) and antiHEV(IgG) were also assessed. RESULTS: In controls, HBV seroprevalence was 5.59% and HCV seroprevalence 4.56%. The risk factors for HBV infection were: age, male gender and South-East region of Romania. The risk factors for HCV infection were: age, female gender, elevated ALT level and the South-East region of Romania. In the very low risk population HBV, HCV, HDV and HEV seroprevalence was: 2.27%, 0%, 0% and 12.5%, respectively. In low risk population the seroprevalence was 2.15%, 1.07%, 0% and 13.98%. In hemodialysis patients, HBV and HCV seroprevalence were 7.91%, respectively 39.26%. HCV-RNA was detectable in 20.69% cases. CONCLUSION: In the South and South-Eastern Romania the seroprevalence of viral hepatitis infections is intermediate, similar to other Romanian regions or the Balkans. PMID- 20361075 TI - Liver biopsy: ultrasonography guidance is not superior to the blind method. AB - AIM: The aim of this study was to evaluate our experience with adequate liver biopsy samples and compare the complication rates of blind and US-guided biopsies, as well as to compare the histological yield of blind and US-guided biopsy specimens. METHODS: We retrospectively analyzed 205 consecutive patients that underwent liver biopsies during a 12-month period. Liver biopsy was performed via the blind method in 152 patients, and via US-guidance in 53 patients. Biopsy specimens were evaluated according to length, presence of fragmentation, crush artifacts, adequacy for diagnosis, and the number of portal tracts and central veins. We also evaluated the rates of mortality and major life threatening complications. RESULTS: All the biopsy specimens were adequate for histological evaluation, except in 8 cases, of which 4 were in the blind biopsy group (2.63%) and 4 were in the US-guided biopsy group (7.54%) (P>0.05). There were no statistically significant differences between the two groups in terms of the specimen fragmentation, or number of portal tracts and central veins in each specimen. Mean specimen length in the US-guided liver biopsy group was 12.58+/ 5.59 mm, and in the blind biopsy group 16.22+/-9.91 mm (P<0.005) . There was no mortality or major complications in either of the two study groups. CONCLUSION: US-guided biopsy was not superior to blind biopsy, an unexpected result. Gastroenterologists/hepatologists should be encouraged to perform liver biopsies via the blind method. PMID- 20361076 TI - Performance of unidimensional transient elastography in staging non-alcoholic steatohepatitis. AB - BACKGROUND/AIMS: Transient elastography (TE) is a noninvasive method for predicting liver fibrosis, mainly validated in patients with viral hepatitis. Information is still limited concerning its performance in non-alcoholic steatohepatitis (NASH) patients. We aimed to assess the value of TE in the prediction of fibrosis stage in NASH as well as the factors determining the discordance between the TE-predicted and the biopsy-proven fibrosis stage in these patients. METHODS: Liver biopsy and TE were performed on 72 consecutive NASH patients. Fibrosis, lobular inflammation, ballooning and steatosis were evaluated (Brunt system). RESULTS: Liver stiffness (LS) values ranged from 2.80 to 16.90 kPa. In the univariate analysis, LS was correlated with fibrosis (r=0.661; p<0.0001), steatosis (r=0.435, p<0.0001), ballooning (r=0.385; p=0.001) and lobular inflammation (r=0.364; p=0.002). In multivariate analysis, only fibrosis significantly correlated with LS (p<0.0001). The median (and range) LS values (kPa) according to the fibrosis stages were: 4.90 (2.80-7.30) for F0; 6.15 (4.80-12.50) for F1; 6.90 (3.30-16.90) for F2 and 14.00 (10.70-14.10) for F3, with significant difference between stages, except for F1-F2 (p=0.249). Cut off values were calculated for predicting each fibrosis stage: 5.3 kPa (AUROC=0.879) for F1; 6.8 kPa (AUROC=0.789) for F2; and 10.4 kPa (AUROC=0.978) for F3. Patients with false-positive results had a significantly higher ALT level than those with concordant results (p=0.039). CONCLUSION: In NASH patients, TE allows a reliable assessment and prediction of liver fibrosis, especially in advanced stages. Steatosis, ballooning and inflammation do not influence liver stiffness. PMID- 20361078 TI - Multiple primary malignancies--epidemiological analysis at a single tertiary institution. AB - BACKGROUND: A literature review on 1,104 269 cancer patients concluded that the prevalence of multiple primary malignancies (MPM) is between 0.73% and 11.7%. MPMs seem to have higher incidence than that influenced by hazard only. AIM: The purpose of this study was to investigate clinically useful information for effective screening for synchronous and metachronous second primary cancers and to identify a potential surveillance protocol. METHODS: Using statistical and epidemiological indicators we evaluated the patients with MPMs (double locations) admitted to the Institute of Oncology "Prof. Dr. Ion Chiricuta", Cluj-Napoca between 2001 and 2004. RESULTS: Out of the 63 cases, 22 cases (34.9%) were synchronous tumors while 41 cases (65.1%) were metachronous tumors, the occurrence interval ranging from 6.2 to 254 months, with an average of 34.6 months for the entire group. Almost half of the metachronous tumors (20 cases) occurred between 6.2 and 24 months while 14 cases (20%) were detected after a 5 year interval. The most frequent malignant associations were ovary-colon, ovary breast, breast-breast. Both primary and secondary tumors tended to be in an advanced stage explained by the low compliance of the patients to follow-up. CONCLUSIONS: The possibility that MPMs exist must always be considered during pretreatment evaluation. Screening procedures are especially useful for the early detection of associated tumors, whereas careful monitoring of patients treated for primary cancer and a good communication between patients and medical care team would ensure an early detection for secondary tumors, and, subsequently, an appropriate management. PMID- 20361077 TI - Isolation and characterization of hepatic cancer cells with stem-like properties from hepatocellular carcinoma. AB - BACKGROUND & AIMS: Major burdens in the treatment of hepatocellular carcinoma (HCC) are the high percentage of recurrence and resistance to chemotherapy. Hepatic cancer stem cells provide a reservoir of cells that can self-renew, maintain the tumor by generating differentiated non-stem cells which make up the bulk of the tumor and are responsible for recurrence after ablative surgery and chemoradiotherapy. The objective of this study was to identify and characterize a self-renewing subpopulation of human liver tumor cells with a distinctive genetic profile that adds the capacity to proliferate despite chemotherapy and promotes cancer recurrence. METHODS: Stemness properties of tumor cells isolated from a HCC biopsy were established by their capacity to form spheroids and by cell proliferation assays. The cells also showed enhanced chemoresistance to cancer drugs. The up-regulation of stem cell markers is proven by immunocytochemistry stainings and reverse transcription-PCR. RESULTS: Cells had a high proliferative potential, even when cultured in medium supplemented with doxorubicin and carboplatin, eliminated Rhodamine 123 immediately in culture and also formed spheroids in suspension. Molecular diagnosis techniques showed that cells expressed the stem cell markers Oct 3/4 and CXCR4. Cells were also positive for CD133 and CD90 cancer stem cell specific markers, with monoclonal antibody staining. CONCLUSION: The unique characteristics identified in cancer stem cells explain self-renewal and could drive metastasis in patients that have received treatment for cancer. The identification and cloning of such cells can aid in developing of better therapeutic approaches for patients with HCC, as chemosensitive pretherapeutic assays or targeted therapies. PMID- 20361079 TI - QUIZ HQ 55. Unusual cause of obstructive jaundice and cholangitis. PMID- 20361080 TI - A large cystic tumor with bile duct communication originating around the hepatic hilum. AB - Biliary cystic tumors are rare neoplasms occurring in the liver and less frequently in the extrahepatic biliary system. Recently, biliary cystic tumors in the liver are thought to be divided into a biliary mucinous cystic neoplasm and intraductal papillary neoplasm of the bile duct. We report a case of a large cystic tumor originating around the hepatic hilum which had luminal communication with the bile duct. A 74 year-old-woman underwent abdominal ultrasonography for a routine checkup. It revealed a large cystic tumor in the liver. CT scan and MRI showed a multilocular cystic tumor about 12 cm in diameter with a mural nodule occupying the medial and anterior segment of the liver. Intraoperative cholangiography showed a communication between the cystic tumor and the bile duct. Central bisegmentectomy of the liver and extrahepatic bile duct resection was performed. A papillary tumor existed in the common hepatic duct and was connected with the cystic tumor in the liver. The tumor was mostly composed of noninvasive papillary adenocarcinoma with adenoma components, and was associated with focal microinvasion of adenocarcinoma. Ovarian-like stroma was not observed. This lesion was diagnosed as a cystic variant of intraductal papillary neoplasm of the bile duct. The patient is alive with no recurrence for 18 months since the surgery. PMID- 20361081 TI - Solitary fibrous liver tumor: is surgical approach the best option? AB - Solitary fibrous tumor of the liver is a rare tumor, where the evolution, malignant potential, and invasive growth have not been well defined. Although most cases are benign, there is no strict correlation between histological findings and biological behavior, and follow-up surveillance is necessary. We present the case of a large solitary hepatic fibrous tumor and its clinical outcome after a 4-year follow-up. Additional therapeutic options are also reviewed. The surgical resection is a plausible therapy in large solitary fibrous tumors of the liver, although liver transplantation may be discussed when the tumor is considered unresectable. However, such aggressive approaches are questionable in asymptomatic patients due to the natural history of this tumor, which is not well known, and the risk of complications. PMID- 20361082 TI - Polypoid vascular and lymphatic malformation of the duodenum: a case report. AB - Polypoid vascular and lymphatic malformation of the small intestine is rare. We report the case of a polypoid vascular and lymphatic malformation of the duodenum in a 58-year-old woman presenting with post-prandial epigastric discomfort. She did not have common symptoms of intestinal vascular and lymphatic malformation, such as gastrointestinal bleeding, steatorrhea, and hypoalbuminemia. A 5.0x0.8-cm semipedunculated polypoid lesion was found in the duodenal bulb with protrusion into the prepyloric antrum and was successfully removed using an endoscopic snare. PMID- 20361083 TI - NSAID-induced colopathy. A case series. AB - The adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract and small intestine are well established. The effect of such therapy on the large intestine, so called NSAID colopathy, is less well described. We present four such cases demonstrating the characteristic endoscopic findings. One case in particular is, to our knowledge, the first report of the natural history of this clinical entity, initially presenting with the acute picture of inflammation and ulceration with subsequent progression to the more chronic development of diaphragm-like fibrous strictures. NSAID-induced colonic damage is a clinically significant condition. Two of our patients presented with bloody diarrhoea while the other two patients developed symptomatic anaemia. With the increasing use of enteric coated and sustained release NSAID preparations this condition is likely to become more frequent. Increasing awareness of its clinical presentation and of its spectrum of endoscopic findings facilitates a more prompt diagnosis and appropriate treatment to be established. PMID- 20361084 TI - State-of-the art endoscopic imaging in lung cancer: should specialties collide or concur? AB - Endoscopic ultrasound has been recently established as a routine diagnostic and staging procedure in lung cancer patients, mainly because of the possibility of tissue sampling. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) represents a method which not only allows the visualization of the upper gastrointestinal tract, but also offers good visualisation of the posterior and inferior mediastinum. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) permits the assessment of the tumors in the anterior mediastinum. Based on previously published literature, it is obvious that this minimally invasive procedure now offers the possibility of tissue diagnosis in mediastinal masses including primary tumours or secondary lesions from both benign and malignant diseases. PMID- 20361086 TI - High concentration of lactic dehydrogenase in small volumes of ascites. PMID- 20361085 TI - The added value of real-time harmonics contrast-enhanced endoscopic ultrasonography for the characterisation of pancreatic diseases in routine practice. AB - Endoscopic ultrasonography is an imaging method used in the diagnosis of pancreatic diseases. The differentiation between inflammatory tumor-like masses and pancreatic adenocarcinoma still remains difficult. Contrast enhanced harmonic endoscopic ultrasonography (CEH-EUS) is a new technique, recently available in commercial use and less evaluated. It is used to characterize the microcirculation in pancreatic disorders--hypervascularized masses such as neuroendocrine tumors or hypovascularized masses such as adenocarcinomas--and to better visualize the necrotic areas in acute pancreatitis and the vascularisation of mural nodules and septa in pancreatic cystic lesions. PMID- 20361087 TI - Hepatic myelolipoma. PMID- 20361088 TI - An unusual cause of Budd-Chiari syndrome: paroxysmal nocturnal hemoglobinuria. PMID- 20361089 TI - Application of non-invasive tests of fibrosis by gastroenterologists and hepatologists. PMID- 20361090 TI - Budd Chiari syndrome and V617F/JAK 2 mutation linked with the myeloproliferative disorders. PMID- 20361091 TI - Diagnosing functional abdominal disorders: evaluations are mandatory in those with warning symptoms. PMID- 20361093 TI - Oxidation of methanol and formaldehyde to CO2 by a photocatalyst with an energy storage ability. AB - A TiO(2)-Ni(OH)(2) bilayer photocatalyst is known as a photocatalyst with energy storage abilities. Oxidative energy from the UV-irradiated TiO(2) underlayer can be stored in the Ni(OH)(2) overlayer. We investigated oxidation and mineralization of methanol and formaldehyde by the stored oxidative energy by mean of gas chromatography. When the methanol concentration in air is as low as 10 ppm, the mass conversion efficiency from methanol to CO(2) is approximately 86%. Formaldehyde can also be oxidized to CO(2) by the stored energy. PMID- 20361095 TI - Total synthesis of (+)-stachyflin: a potential anti-influenza A virus agent. AB - The first enantioselective total synthesis of (+)-stachyflin, a potential anti influenza A virus agent, was achieved; the method features a BF(3).Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction to stereoselectively form the requisite pentacyclic ring system in one step. PMID- 20361094 TI - Cytokine-associated drug toxicity in human hepatocytes is associated with signaling network dysregulation. AB - Idiosyncratic drug hepatotoxicity is a major problem in pharmaceutical development due to poor prediction capability of standard preclinical toxicity assessments and limited knowledge of its underlying mechanisms. Findings in animal models have shown that adverse effects of numerous drugs with idiosyncratic hepatotoxicity in humans can be reproduced in the presence of coincident inflammatory cytokine signaling. Following these observations, we have recently developed an in vitro drug/inflammatory cytokine co-treatment approach that can reproduce clinical drug hepatotoxicity signatures-particularly for idiosyncratic drugs-in cultured primary human hepatocytes. These observations have suggested that drug-induced stresses may interact with cytokine signaling to induce hepatic cytotoxicity, but the hepatocyte signaling mechanisms governing these interactions are poorly understood. Here, we collect high-throughput phosphoprotein signaling and cytotoxicity measurements in cultured hepatocytes, from multiple human donors, treated with combinations of hepatotoxic drugs (e.g. trovafloxacin, clarithromycin) and cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-1 alpha, and interleukin-6). We demonstrate, through orthogonal partial least-squares regression (OPLSR) modeling of these signal-response data, that drug/cytokine hepatic cytotoxicity is integratively controlled by four key signaling pathways: Akt, p70 S6 kinase, MEK-ERK, and p38 HSP27. This modeling predicted, and experimental studies confirmed, that the MEK ERK and p38-HSP27 pathways contribute pro-death signaling influences in drug/cytokine hepatic cytotoxicity synergy. Further, our four-pathway OPLSR model produced successful prediction of drug/cytokine hepatic cytotoxicities across different human donors, even though signaling and cytotoxicity responses were both highly donor-specific. Our findings highlight the critical role of kinase signaling in drug/cytokine hepatic cytotoxicity synergies and reveal that hepatic cytotoxicity responses are governed by multi-pathway signaling network balance. PMID- 20361096 TI - A novel electrochemical DNAzyme sensor for the amplified detection of Pb2+ ions. AB - A novel amplification strategy based on DNAzyme functionalized gold nanoparticles was employed to enhance the sensitivity of an electrochemical sensor for detection of Pb2+. The detection limit is 0.028 nM, which is much lower than for other electrochemical DNAzyme sensors. PMID- 20361097 TI - Gold and palladium combined for the Sonogashira-type cross-coupling of arenediazonium salts. AB - The Sonogashira-type cross-coupling of arenediazonium salts is reported for the first time using a Pd-Au dual catalytic system. PMID- 20361099 TI - Complexation between pentiptycene-based mono(crown ether)s and tetracationic cyclobis(paraquat-p-phenylene): who is the host or the guest? AB - Pentiptycene-based mono(crown ether)s and tetracationic cyclobis(paraquat-p phenylene) can form 1 : 1 stable complexes in solution and in the solid state, in which both of the components act as the host as well as the guest. PMID- 20361100 TI - Alkali metal cation doped Al-SBA-15 for carbon dioxide adsorption. AB - Mesoporous aluminosilicate adsorbents for carbon dioxide were prepared by the grafting of aluminium into SBA-15 silica using an aqueous solution of aluminium chlorohydrate. As the ion exchange sites are primarily associated with the presence of tetrahedrally coordinated aluminium, extra-framework aluminium on the SBA-15 surface was inserted into the silica matrix by a treatment with an aqueous solution of NH(4)OH. Synthesized mesoporous aluminosilicate preserving all the characteristic features of a mesoporous molecular sieve was finally modified by the alkali metal cation exchange. To examine carbon dioxide adsorption on prepared materials, adsorption isotherms in the temperature range from 0 degrees C to 60 degrees C were measured. Based on the known temperature dependence of adsorption isotherms, isosteric adsorption heats giving information on the surface energetics of CO(2) adsorption were calculated and discussed. The comparison of carbon dioxide isotherms obtained on aluminosilicate SBA-15, aluminosilicate SBA-15 containing cations Na(+) and K(+) and activated alumina F 200 reveals that the doping with sodium or potassium cations dramatically enhances adsorption in the region of equilibrium pressures lower than 10 kPa. Therefore, synthesized aluminosilicate adsorbents doped with Na(+) or K(+) cations are suitable for carbon dioxide separation from dilute gas mixtures. PMID- 20361098 TI - Metal-dioxygen and metal-dinitrogen complexes: where are the electrons? AB - Transition-metal complexes of O(2) and N(2) play an important role in the environment, chemical industry, and metalloenzymes. This Perspective compares and contrasts the binding modes, reduction levels, and electronic influences on the nature of the bound O(2) or N(2) group in these complexes. The charge distribution between the metal and the diatomic ligand is variable, and different models for describing the adducts have evolved. In some cases, single resonance structures (e.g. M-superoxide = M-O(2)(-)) are accurate descriptions of the adducts. Recent studies have shown that the magnetic coupling in certain N(2)(2-) complexes differs between resonance forms, and can be used to distinguish experimentally between resonance structures. On the other hand, many O(2) and N(2) complexes cannot be described well with a simple valence-bond model. Defining the situations where ambiguities occur is a fertile area for continued study. PMID- 20361101 TI - Copper-promoted N-cyclopropylation of anilines and amines by cyclopropylboronic acid. AB - Reaction of anilines, primary and secondary aliphatic amines with cyclopropylboronic acid in dichloroethane in the presence of Cu(OAc)(2) (1 equiv.), 2,2'-bipyridine (1 equiv.) and sodium carbonate or sodium bicarbonate (2 equiv.) under air atmosphere afforded the corresponding N-cyclopropyl derivatives in good to excellent yields. PMID- 20361102 TI - Biomimetically relevant self-condensations of C5 units derived from lysine. AB - In various conditions, dimerization of pentanedial-derived units gives rise to interesting skeletons, which are reminiscent of alkaloids known to be biosynthesized in Nature via lysine metabolism. PMID- 20361103 TI - Label-free and naked eye detection of PNA/DNA hybridization using enhancement of gold nanoparticles. AB - Utilizing a gold enhancement process after inducing electrostatic interaction between positively charged gold nanoparticles and negatively charged target DNA hybridized to neutral PNA capture probes, a new method for label-free detection of DNA was developed and successfully applied to detect H5-type DNA. PMID- 20361104 TI - Insights into the mechanism of carbonate formation through reductive cleavage of carbon dioxide with low-valent uranium centers. AB - The low-valent U(III) complexes [((t-BuArO)3mes)U] and [((AdArO)3N)U] react with CO2 to form the bridging carbonate complexes [{((t-BuArO)3mes)U}2(mu kappa2:kappa2-CO3)] and [{((AdArO)3N)U}2(mu-eta1:kappa2-CO3)]. Uranium(IV) bridging oxo complexes have been determined to be the intermediate in these transformations. PMID- 20361105 TI - [Mental health and the law: ethical, scientific and organizational issues]. PMID- 20361106 TI - [Mentally ill and criminalized: testimony of a dual marginalization]. AB - Based on two open-ended interviews with people suffering from a mental illness and who have been incarcerated, this article explores their perspectives on both health and justice systems. In their view, there is a divide between the needs of people with mental health problems and the care that is offered. The difficult juncture between needs and services seems to have numerous explanations (prejudice, lack of training of personnel, difficult administrative process, lack of communication between "inside" and "outside"); and the elements that could facilitate this juncture appear to be scarce (mutual help among inmates, community based mental help organizations). PMID- 20361107 TI - [Between the legal system and medical and psychosocial intervention: the reality of family members of individuals with mental illness]. AB - In this article, the author examines the impact of judicial intervention of individuals with mental illness on family members. The author subunits the hypothesis that an offer of more diversified services could reduce legal intervention of these individuals and consequently attenuate the devastating effects on family members. According to the families' equation, the more services will be developed and adapted, the less frequent family will have to call upon the legal system to intervene and fewer individuals with mental illness will find themselves behind bars. PMID- 20361108 TI - [Patients' rights: a threat to caregivers?]. AB - In recent years, advocacy groups promoting patients' rights have lead to significant changes including the implementation of policies reducing measures of seclusion and restraint of patients with mental disorders. These policies are unanimous in that constraint is to be used as a solution of last resort and must be applied only under unique and exceptional circumstances. The reaction of healthcare workers to these new policies and to increase attention of patients'rights is often ignored in the current literature. Indeed, it is not rare for healthcare workers to come to think that the patients' rights supersede their own. In this article, this issue is examined from two perspectives. First, the author examines experiences of healthcare workers followed by a presentation of ethical and legal issues arising from the policies which promote the reduction of seclusion and restraint measures. PMID- 20361109 TI - [Psychiatric advance directives and the role of autonomy]. AB - Although psychiatric advance directives (PADs) are grounded in the ethics of autonomy, the relationship between the two is unclear. PADs are legal documents that allow individuals with mental illness to record their treatment preferences should they become incompetent in the future. The relationship between autonomy and PADs has been discussed in ethical, legal, and philosophical terms, but has not been clearly operationalized for clinical purposes. Autonomy is a fundamental ethical value that includes having the independence from outside controlling influences and the mental capacity to direct one's personal actions. Individuals with mental illness sometimes require assistance to understand their ethical and legal rights with respect to autonomous choice, and professional stakeholders need education regarding the importance of autonomy for clinical practice. Competency to consent to treatment is the mental prerequisite that ensures individuals with mental illness are able to complete PADs with insight, whereas autonomy is the value that empowers individuals to work towards their recovery. PMID- 20361110 TI - [Canadian Mental Health Law: recognizing and rectifying a problematic situation]. AB - This article explores several conundrums and attempts to identify ways of redirecting the Canadian ship of state. It first presents an overview of some of the salient features of the array of mainly coercive provincial and territorial mental health statutes. The failure in the main of the Charter to deliver on its early ostensible promises for people with mental health problems is assessed. Next, the author argues that extant legislation remains anchored in the medical model, when other human rights promoting paradigms transforms the statutory agenda. PMID- 20361111 TI - [Canadian Mental Health Law: accelerating the redirection of the Ship of State]. AB - In this article, some hopeful outlooks on the evolution of the law are identified and ways of assessing the state and progress of legislation are advanced, drawing from international organizations and some inspiring efforts in other countries. Potential contributors to the evolution of Canadian mental health law are surveyed. The author concludes that there are coherent ways of changing tack, although in this fraught legislative field, no one can make confident predictions about the future. PMID- 20361112 TI - [Characteristics of adolescent offenders receiving services in juvenile centers in Quebec (Centres jeunesse du Quebec, CJQ)]. AB - This study aims at establishing a comparative psychological profile of male and female adolescents at the moment of the application of measures in juvenile centers in Quebec (centres jeunesse du Quebec, CJQ) as well as their family and social characteristics. The study compares 213 adolescents (12-17 years old) receiving services in CJQ in accordance with the juvenile offenders act (Loi sur les jeunes contrevenants), with 213 adolescents from high schools of impoverished neighbourhoods. Results reveal serious problems of adaptation, external disorders and interiorized disorders and a regular substance abuse among many juvenile offenders. These problems are much more frequent in CJQ than within the juvenile population. The situation of these adolescents is worrisome, given that a high prevalence of depression and sexual victimisation is also observed in females. Finally, families whose adolescent receives services in CJQ have less financial, personal and social resources, as well as more difficulty exercising their parental role compared to parents in the general population. In conclusion, recommendations are proposed concerning psychosocial services necessary for these adolescents and their families. PMID- 20361114 TI - [Mental Health courts: therapeutic jurisprudence in action]. AB - In Quebec, as elsewhere in North America, psychiatric deinstitutionalization, lack of community mental health resources as well as legislative changes to civil and criminal codes have led to an increased probability that individuals with a mental illness come into contact with the criminal justice system. Based on the principle of therapeutic jurisprudence, mental health courts constitute emerging diversion programs, taking place within the court, implemented to offer an alternative to incarceration for individuals with a mental illness. This article offers a critical synthesis of the scientific literature on the topic. The authors first present the context in which mental health courts were developed ; describe their objectives and functioning ; and introduce the Montreal Mental Health Court pilot project, renamed PAJ-SM (Plan d'Accompagnement Justice et Sante) the first of its kind in Quebec. The paper examines the research on mental health courts and tackles some of the stakes of diversion programs. The challenges and limits inherent to specialized courts are discussed as well as methodological obstacles related to the study of these complex intervention programs. The authors conclude that mental health courts offer promising intervention venues, but that they do not constitute a panacea to resolving all issues related to the contact of mentally ill individuals with the justice system. Mental health courts must be accompanied by other intervention strategies for persons with mental health problems at all stages of the criminal justice process. PMID- 20361113 TI - [Prescription of psychotropic medication in inmates of Quebec's correctional facilities]. AB - In this article, the authors attempt to better examine the practice of prescription of psychotropic medication of inmates of Quebec's correctional facilities. Although prescription of this medication is considered the most widespread "psychiatric treatment," studies on the prevalence of these prescriptions remain scarce. The study includes a sample of 671 inmates, 500 men and 171 women. Globally, 40,3 % of inmates have received at least one prescription for psychotropic medication in the period between 2002 and 2007. Results show that women are more likely than men to have been prescribed medication. Inmates who have received at least one prescription are older than other inmates. Most prescriptions have been given by physicians and the cases of polypharmacy are numerous. On a period of five years, the class of medication the most widely prescribed is the following: anxiety/hypnotic medication, antidepressants and antipsychotic medication. The authors conclude that further analysis of factors associated with prescription of this class of medication of this population is needed. PMID- 20361115 TI - [Attention deficit hyperactivity disorder (ADHD) in preschoolers: nature, assessment and treatment]. AB - Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behaviour problem in school-age children. Although more and more preschool-age children are referred in clinical settings for typical ADHD symptoms, few studies have examined the nature, the assessment as well as the treatment of ADHD in this age group. This literature review addresses the nature, the assessment, and the treatment of ADHD during the preschool period. The main themes reviewed are: prevalence, symptomatology, etiology, comorbidity, consequences on normal development and adaptation of the child, evolution of symptoms from preschool to school period, difficulties related to diagnosis, assessment modalities, psychosocial treatment, and pharmacological treatment. PMID- 20361116 TI - [The Projet PIE: a promising strategy to reach elders with a mental health problem]. AB - Approximately fifty percent of older adults with a mental health problem do not receive services. A proactive outreach strategy, Project PIE (Prevention Intervention-Education) relies upon the assistance of non-traditional referral sources, namely community liaisons, to identify and refer to the CSSS vulnerable or isolated elders with a mental health problem. An evaluation of this project reveals encouraging results. The project appears useful, relevant and efficient to detect elders with a mental health problem and offer the required assistance. This project also appears to be a means to foster social solidarity. PMID- 20361117 TI - [Brief intervention in psychiatric consultation]. AB - This essay presents a perspective on intervention in psychiatric consultation based on the patient's subjective experience as supported by Kendler in 2005 in the American Journal of Psychiatry in his position against biological reductionism in psychiatry, distinguishing the psychic approach from the biological. The paper presents aspects of the setting and major features of the assessment in the consultation process, then proceeds to discussing principles of intervention as to specify dimensions of the psychiatric intervention in this particular context. PMID- 20361118 TI - Is a diagnosis of metabolic syndrome applicable to children? AB - OBJECTIVE: To present the components of the metabolic syndrome in children and adolescents and to discuss how they are assessed in the pediatric population in addition to presenting the major metabolic syndrome classifications for the age group. SOURCES: A review of literature published from 1986 to 2008 and found on MEDLINE databases. SUMMARY OF THE FINDINGS: The prevalence of childhood obesity has been increasing globally over recent decades and as a result its complications, such as diabetes mellitus, arterial hypertension and dyslipidemia, have also increased. The concept of metabolic syndrome, already common with adults, is now beginning to be applied to children through classifications using the criteria for adults modified for the younger age group. Notwithstanding, these classifications differ in terms of the cutoff points used and whether they employ body mass index or waist circumference to define obesity. The review presents these classifications, highlighting the points on which they differ and the debate about them. CONCLUSIONS: If childhood obesity goes untreated, it will have severe consequences in the future. A number of models for classifying metabolic syndrome in children have been published, but there is considerable diversions between them. The criteria for classifying metabolic syndrome in children therefore need to be standardized in order to identify those people at greatest risk of future complications. PMID- 20361119 TI - Assessing clinical and spirometric control and the intensity of the inflammatory process in asthma. AB - OBJECTIVES: To review the role of clinical assessment, quality of life assessment, spirometry, bronchial responsiveness test and inflammatory markers for asthma assessment. SOURCES: Search run on MEDLINE and LILACS. SUMMARY OF THE FINDINGS: Clinical assessment aids with assessing asthma control and is widely recommended. However, patients may have airway inflammation and obstruction despite normal clinical findings. Spirometry quantifies the degree of airway obstruction and helps with diagnosis, while the bronchial responsiveness test may be indicated for when asthma is suspected but spirometry is normal. The results of assaying the inflammatory markers in exhaled breath condensate, induced sputum, bronchoalveolar lavage and bronchial biopsy specimens are abnormal in asthma patients, but these are complex techniques almost always restricted to research. Fractional exhaled nitric oxide (FeNO) is elevated in patients with asthma, is reproducible and noninvasive and reduces with treatment. Studies have investigated using FeNO to help with adjusting inhaled corticoid dosages, but the benefits are not clear. CONCLUSIONS: A range of different methods are needed to accurately assess disease control, all with their advantages and limitations. Clinical and functional assessment is useful for diagnosing asthma, but is of limited use for precisely evaluating the intensity of the inflammatory process in the airways. More randomized and controlled studies with adequate statistical power should be carried out to investigate the true utility of noninvasive inflammatory markers, especially FeNO, for asthma management. PMID- 20361120 TI - Open challenge for the diagnosis of cow's milk protein allergy. AB - OBJECTIVE: To report the results of open challenge tests performed in children fed with cow's milk-free diet. DESCRIPTION: Cross-sectional study evaluating cow's milk open challenge performed under supervision in a hospital setting during 2.5 hours and ambulatory follow-up for 30 days when no immediate reaction occurred. One hundred and twenty-one patients were included, with ages between 4 and 95 months. Cow's milk open challenge tests were positive in 28 patients (23.1%). A clinical manifestation of cow's milk allergy different from the one presented at diagnosis occurred in 12 (24.9%) patients with positive challenge. Positive challenge was more frequent (p = 0.042) in patients fed with extensively hydrolyzed formulae or amino acid-based formulae (30.3%) when compared to those fed with other exclusion diets (14.5%). CONCLUSION: Open challenge allowed the interruption of exclusion diet in a significant proportion of the patients. PMID- 20361121 TI - Acquisition of motor abilities up to independent walking in very low birth weight preterm infants. AB - OBJECTIVE: To determine chronological and corrected ages at acquisition of motor abilities up to unaided walking in very low weight preterms and to determine up to what point it is necessary to use corrected age. METHODS: This was a longitudinal study of preterms with birth weight < 1,500 g and gestational age < or = 34 weeks, free from neurosensory sequelae, selected at the high-risk infants follow-up clinic at the Hospital das Clinicas, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP) in Botucatu, Brazil, between 1998 to 2003, and assessed every 2 months until acquisition of unaided walking. RESULTS: Nine percent of the 155 preterms recruited were excluded from the study, leaving a total of 143 patients. The mean gestational age was 30+/-2 weeks, birth weight was 1,130+/-222 g, 59% were female and 44% were small for gestational age. Preterms achieved head control in their second month, could sit unaided at 7 months and walked at 12.8 months' corrected age, corresponding to the 4th, 9th and 15th months of chronological age. There were significant differences between chronological age and corrected age for all motor abilities. Preterms who were small for their gestational age acquired motor abilities later, but still within expected limits. CONCLUSIONS: Very low weight preterms, free from neurosensory disorders, acquired their motor abilities within the ranges expected for their corrected ages. Corrected age should be used until unaided walking is achieved. PMID- 20361122 TI - Characterization of rotavirus strains from day care centers: pre- and post rotavirus vaccine era. AB - OBJECTIVES: In 2006 the rotavirus vaccine was included in the Brazilian Immunization Program. The aim of this study was to report the results of a 5-year surveillance study of rotavirus strains in children < 5 years with acute gastroenteritis from day care centers in the state of Sao Paulo, Brazil. METHODS: This retrospective study was conducted with 30 day care centers from 2004 to 2008 with convenient surveillance fecal specimens, investigated by ELISA, SDS-PAGE, RT PCR and gene sequencing to genotype characterization. RESULTS: Rotavirus infection was detected in 28.3% of samples (38/134). The most frequent genotypes detected were G9P[8] and G1P[8] in 2004; G1P[8] in 2005; GNTP[NT] in 2006; G2P[4] in 2007; and there were no cases in 2008. Mixed infections were not observed. Detection rate declined from 65.7% (23/35) in 2004 to 50% (9/18) in 2007. CONCLUSIONS: Genotype distribution varied according to collection year, accompanied by a reduction in detection rate. Use of rotavirus vaccine requires implementation of post-marketing surveillance to monitor rotavirus strain diversity and its efficacy against possible new emerging genotypes. PMID- 20361123 TI - Ear piercing as a risk factor for contact allergy to nickel. AB - OBJECTIVES: To determine the prevalence of metal contact allergy among the children seen at a health center children with metal allergies in terms of risk factors. METHODS: This was an uncontrolled cross-sectional study undertaken at a health center in Belo Horizonte, Brazil. Children aged from 0 to 12 years were recruited when they presented at the health center for routine pediatric consultations and were given contact tests for chrome, cobalt and nickel. Statistical analyses were conducted on test readings taken at 96 hours. Results classed as weak (+), strong (++) or extreme (+++) were defined as "reaction," while those classed as doubtful, negative or irritant were defined as "no reaction." RESULTS: A total of 144 children completed the study protocol. Of these, 4.9% exhibited a reaction to chrome, 9.7% to cobalt and 20.1% to nickel. Patients with pierced ears were more likely to react to nickel than those without pierced ears (p = 0.031 and odds ratio = 2.8). CONCLUSIONS: In view of the current tendency for the prevalence of nickel allergy to increase, parents should be warned about its association with ear piercing. Further studies are needed to determine the ideal age for ear piercing and the ideal materials for earrings. PMID- 20361124 TI - Serum levels of caffeine in umbilical cord and apnea of prematurity. AB - OBJECTIVE: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. METHODS: A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxanthine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. RESULTS: Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 microg/mL (0.2-9.4 microg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3+/-4.14 hours) than those with undetectable levels (54.2+/-6.26 hours). CONCLUSION: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells. PMID- 20361125 TI - Turner syndrome: a pediatric diagnosis frequently made by non-pediatricians. AB - OBJECTIVE: To analyze the clinical features of patients with suspected diagnosis of Turner syndrome (TS) in a reference service. METHODS: Retrospective analysis of 425 patients: data pertaining to age, height and pubertal stage at diagnosis, as well as the specialty of the physician who referred the patient were collected. Patients with and without TS were compared, as well as those with TS according to specialty of the physician; the correlation between age and height at diagnosis was analyzed. RESULTS: TS diagnosis was made in 36.9% of the cases with a mean age of 12.0 years, and height z score = -3.09; pubertal delay was found in 71.4% of the 63 patients aged more than 13 years. When compared to the other patients, girls with TS had a higher height deficit and higher frequency of pubertal delay. TS patients referred by pediatricians were significantly younger (9.3 years vs. 15.4 years), but their height and frequency of pubertal delay were similar to those referred by non-pediatricians. There was a significant negative linear correlation between age and height in the total amount of patients with TS, but not among those referred by non-pediatricians. CONCLUSIONS: Mean age at TS diagnosis is still higher than that observed in developed countries, and the presence of spontaneous pubertal signs and/or less pronounced growth deficit in some cases may contribute to delayed clinical suspicion of TS. Information required for early TS diagnosis must be spread among pediatricians and non pediatricians. PMID- 20361126 TI - Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major. AB - OBJECTIVE: To comparatively evaluate P-wave dispersion (PWD) in patients with beta-thalassemia major (TM) and healthy control subjects for the early prediction of arrhythmia risk. METHODS: Eighty-one children with beta-TM, aged 4-19 years, and 74 healthy children (control group) underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS: There was a statistically significant difference between study and control groups in peak early (E) mitral inflow velocity and E/late (A) velocity ratio. Maximum P wave duration and PWD were found to be significantly higher in beta-TM patients than in control subjects. CONCLUSIONS: Increased PWD in our beta-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias. PMID- 20361127 TI - Is obesity an emerging problem in Brazilian children and adolescents? PMID- 20361128 TI - Sweat testing: can the conductivity analysis take the place of the classic Gibson and Cooke technique? PMID- 20361129 TI - [Prognostic factors and mortality in immunocompetent adult patients hospitalized with community-acquired pneumococcal pneumonia]. AB - BACKGROUND: Streptococcus pneumoniae is the main cause of community-acquired pneumonia in adults. AIM: To describe baseline characteristics, risk factors and clinical outcomes of adult patients hospitalized with pneumococcal pneumonia. MATERIAL AND METHODS: Prospective study of adult patients admitted for a community acquired pneumonia in a clinical hospital. Immune deficient patients and those with a history of a recent hospitalization were excluded. RESULTS: One hundred fifty one immuno-competent patients, aged 16 to 92 years, 58% males, were studied. Seventy-five percent had other diseases, 26% were admitted to the intensive care unit and 9% needed mechanical ventilation. There were no differences in clinical features, ICU admission or hospital length of stay among bacteremic and non-bacteremic patients. Thirty days lethality for bacteremic and non-bacteremic patients was 10.9% and 11.5%, respectively. The predictive values for lethality of Fine pneumonia severity index and CURB-65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older) had an area under the ROC curve of 0.8 and 0.69, respectively. Multivariate analysis disclosed blood urea nitrogen over 30 mg/ dL (odds ratio (OR), 6.8), need for mechanical ventilation (OR, 7.4) and diastolic blood pressure below 50 mmHg (OR, 3.9), as significant independent predictors of death. CONCLUSIONS: Pneumococcal pneumonia was associated with a substantial rate of complications and mortality. Clinical presentation and outcome did not differ significantly among patients with and without bacteremia. PMID- 20361130 TI - [Direct costs of pharmacotherapy for acute leukemia at a Regional Hospital in Chile]. AB - BACKGROUND: In Chile, leukemia is one of the diseases whose treatment is guaranteed by a special law called AUGE (universal access and explicit guaranties). Therefore, the knowledge of its treatment costs is of utmost importance. AIM: To determine and to characterize the direct costs of pharmacotherapy for leukemia at a regional hospital in Chile. MATERIAL AND METHODS: Data were retrospectively obtained from electronic and manual records of the hospital for all patients treated for leukemia between 2003 and 2006. Patients were classified into four groups: pediatric and adult patients treated for acute lymphocytic leukemia (ALL children and ALL adults, respectively), and pediatric and adult patients treated for acute myelogenous leukemia (AML children and AML adults, respectively). RESULTS: Total accumulated costs of pharmacotherapy for acute leukemia between 2003 and 2006 were 304,724,845 Chilean pesos (USD 574,952). The higher total or per patient costs, were generated by drugs for chemotherapy compared to other required medications. The exception were AML children, where support drugs, such as antimicrobials, ant emetic drugs and colony stimulating factors, generated the higher costs per patient. Among ALL adults, AML children and AML adults, the costs were concentrated in the first 6 months of treatment. NO children followed this tendency concentrating the costs between the seventh and twenty-fourth months. CONCLUSIONS: Annual costs of pharmacotherapy per patient for acute leukemia in this regional hospital were approximately USD 4,717. Chemotherapy was the item with the greatest impact on cost. PMID- 20361131 TI - [A survey about the competences required by primary health physicians in Chile]. AB - BACKGROUND: Primary health care is considering the cornerstone of health care in Chile. Its efficiency is strongly influenced by the quality and competences of physicians that are responsible for health care at this level. AIM: To define the features and competences that should have primary care physicians. MATERIAL AND METHODS: A group of experts that could be physicians or other professionals working in primary health care were invited to answer electronically a structured questionnaire containing a list of 71 competences, for a basic and an expert level of physician, using the Delphi method. Competences were classifying as "desirable" or "indispensable". If there was lack of consensus in the importance given to a specific competence, the researchers defined its importance. RESULTS: Thirty-eight professionals (50% physicians) were inviting to participate and 16 answered the questionnaire. The competence profile defined for basic physicians has 13 knowledge items, 24 skills and 16 attitudes. The figures for advanced physicians are 29 knowledge items, 37 skills and 20 attitudes. CONCLUSIONS: This list of competences should been considered by medical schools to adapt undergraduate training of future physicians. PMID- 20361132 TI - [Rates of Chlamydia trachomatis and Neisseria gonorrhoeae in Chilean adolescents]. AB - BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae are common sexually transmitted diseases among young women and little has been doing to study them in Chilean adolescents. AIM: Determine the rates of C trachomatis and N gonorrhoeae in Chilean young women. MATERIAL AND METHODS: Urine samples were obtained from 203 sexually active females under 25 year-old, who attended hospitals from either high or low-income areas in Chile's capital, Santiago. C trachomatis and Ngonorrhoeae were detected by nucleic acid amplification testing. RESULTS: Seven percent of samples were positive for C trachomatis. AU samples were negative for N gonorrhoeae. Among pregnant women, 19% of samples were positive for C trachomatis, while non-pregnant women were positive on 5.5% (p =0.04). Systematic use of barrier contraception was referring by 12% of women. AU of the latter was free of C trachomatis. No association was observing between age, number of sexual partners, age of first sexual intercourse, and presence of uro-gynecological symptoms, socioeconomic status and the rate of C trachomatis. CONCLUSIONS: Seven percent of this group of Chilean young women was infected with C trachomatis. The figure rises to 19% if pregnant. Surveillance and screening programs should been implemented to prevent sequels on this vulnerable population. PMID- 20361133 TI - [Compliance with guidelines for the management of community acquired pneumonia at primary health care centers]. AB - BACKGROUND: Community acquired pneumonia (CAP) has a high mortality rate among older people. To increase its treatment efficiency, the Chilean Ministry of Health elaborated a clinical management guideline for CAP. AIM: To assess the degree of compliance with the clinical guidelines for CAP among professionals working at primary health care centers. MATERIAL AND METHODS: A follow up of a cohort of 2,797 subjects aged 67 years or more, incorporated to a clinical study. All cases of bronchopneumonia or pneumonia diagnosed at primary health care centers between September 2005 and June 2008 were recorded. RESULTS: During the follow up period, 192 cases of CAP were diagnosed. A chest X-ray was requested in 81% of cases and a confirmation consultation was done in 58%. Amoxicillin/ Clavulanic acid was the most common antimicrobial prescription in 61% of cases, followed by Clarithromycin in 17% and Amoxicillin in 12%. The antimicrobial used was not registered in 5% of cases. CONCLUSIONS: The clinical guidelines improve the efficiency of CAP treatment and decrease complications. However, these guidelines must been complemented with an adequate training and supervision of health care teams. PMID- 20361134 TI - [Minimally invasive correction of pectus excavatum among adults. Report of eighteen cases]. AB - BACKGROUND: A minimally invasive technique or Nuss procedure was devised for children with pectus excavatum (funnel chest), but it is also used in adult patients. AIM: To report the experience with the Nuss procedure in adults' patients with pectus excavatum. MATERIAL AND METHODS: Prospective study of patients operated between January 2007 and January 2009. Clinical features, symptoms, operative time, postoperative complications, hospital stay and quality of life, using the Nuss questionnaire adapted for adults, was recorded. RESULTS: Eighteen patients aged 18+/-2 years (14 males) were operated. Seven patients had scoliosis, two had depression, two had asthma and one had a Marfan syndrome. AU patients were concerned about aesthetic issues, nine had dyspnea, three had compression of cardiac cavities and three had pulmonary function disturbances. Haller index was 3.8. Mean operative time was 92 minutes. Postoperative complications were a pneumothorax without chest tube management in two patients, a peridural hematoma in one patient and a bar stabilizer infection that required a reoperation in one patient. No patient died and the mean hospital stay was six days. The Nuss questionnaire scores in the pre and postoperative periods were 33 and 48, respectively (p <0.05). CONCLUSIONS: Nuss operation is feasible and safe in adults with pectus excavatum. PMID- 20361135 TI - [Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism]. AB - BACKGROUND: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. AIM: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT. MATERIAL AND METHODS: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. RESULTS: Eighty-eight operated patients, aged 58+/ 15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6+/- 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98%) at 24 hours and 50 of 52 patients followed for six months (96%). The pathological study disclosed an adenoma in 69 (78%), and multiglandular disease in 16 (18%), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97% and 100% of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94% and 100%, respectively. CONCLUSIONS: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT. PMID- 20361136 TI - [Gigantic cystic splenic lymphangioma. Report of one case]. AB - Splenic lymphangiomas are benign primary simple or multiple tumors. They are incidentally diagnosed in children and people younger than 20 year-old. We report a 26-year-old female presenting with a history of five months of abdominal pain localized over the left upper hemi abdomen. A computed tomographic abdominal scan demonstrated a cystic tumor of 16 cm diameter originating from the spleen. Hydatic serology was negative and all blood tests were normal. At surgery, a spienic cyst was found and almost all the cystic wall was excised, leaving only a small portion attached to the spleen. The pathological report described spienic parenchyma with endothelial lining over the internal side of the cyst. Immunohystochemical stains of the endothelial cells were positive for VIII Factor and D2-40 that are specific for lymphatic endothelium, yielding the final diagnosis of a cystic spienic lymphangioma. PMID- 20361137 TI - [Listeria monocytogenes rhomboencephalitis. Report of three cases]. AB - An unusual number of cases of rhomb encephalitis have occurred in Chile because of the increased frequency of infections caused by Listeria monocytogenes. We report three females aged 36, 40 and 55 years, with the disease. All presented with a prodrome characterized by headache, nausea, vomiting and fever, followed by ataxia and unilateral palsies of the third, seventh and twelfth cranial nerves. One patient presented also a hemi-hypoesthesia. Magnetic resonance showed lesions in the posterior aspect of the brain stem, specifically in relation to the floor of the fourth ventricle. Blood cultures were positive for Listeria monocytogenes. PMID- 20361138 TI - [Hyponatremia associated to pituitary adenomas. Report of three patients]. AB - Severe hyponatremia occurring as the presenting feature of hypopituitarism secondary to pituitary adenomas is rare. We report three patients with this condition: Two elderly males (74 and 78 year-old) presenting with impaired consciousness and low plasma sodium after an episode of diarrhea and a 56-year old male presenting with impaired consciousness after an episode of vomiting. All had clinical features of hypopituitarism and pituitary adenomas were found on imaging studies. Two were subjected to a trans sphenoidal resection of the adenoma. PMID- 20361139 TI - [Pulmonary tumor embolism: Report of two cases]. AB - Dyspnea and hypoxemia in a patient with cancer may have several causes, including infections, thromboembolism, metastases, and pulmonary injuries by drugs. We report a 47-year-old female with breast cancer and a 70-year-old male with urinary bladder cancer who were admitted for dyspnea, hypoxemia and pulmonary hypertension. Chest X rays and CT scans were normal. The ventilation-perfusion scintigram was highly suspicions of thromboembolism in the female. The male died 16 hours after admission and the post mortem examination revealed the presence of tumor cells in the pulmonary vasculature. PMID- 20361140 TI - [An update on the pathogenesis of celiac disease]. AB - Celiac disease (CD), with a 1% worldwide prevalence, is an enteropathy caused by an autoimmune reaction to gluten in genetically susceptible individuals, which codify for histocompatibility molecules HLA DQ-2/DQ-8. From the anatomical point of view, CD is characterized by intestinal villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (IELs) and leukocyte infiltration of the lamina propriety. Patients achieve a complete clinical and endoscopic remission with a gluten free diet. However, symptoms and anatomical alterations recur when this protein is reintroduced in the diet. The pathogenic mechanisms in this disease are not yet well understood, but it is clear that genetic, environmental and immunological factors play a role. The latter are the focus of this review, since this is the only autoimmune disease whose precipitating factor for immunological tissue damage is known. PMID- 20361141 TI - [Recent advances in the pathogenesis of diabetic embryopathy]. AB - The congenital malformations in the off spring of diabetic mothers are the result of a multifactorial process. Susceptibility to the effects of maternal diabetes in the pathogenesis of these anomalies is influenced by the genetic background, indicating that there are polymorphic genes that modify the cellular response to hyperglycemia. The modifier genes for the teratogenic effect of maternal diabetes are yet unknown. An excessive glucose supply to embryonic tissues leads to a state of oxidative stress, which affects the expression of genes encoding scavenging enzymes such as super oxide dismutase (SOD) and catastases and activates development genes such as PAX3, involved in neural tube defects. Cell proliferation and cell death are important mechanisms underlying malformations in infants born to diabetic mothers. There is an increase of apoptotic Bax and caspase-3 proteins and a low expression of Bcl-Z ant apoptotic protein in embryos exposed to a diabetic environment. Hyperglycemia decreases intracellular levels of reduced GSH, prostaglandin EZ (PGEZ) and DNA synthesis in embryo's tissues. Understanding the molecular pathogenesis of diabetic embryopathy will allow the use of effective therapies for the prevention of teratogenic effects in diabetic mothers. PMID- 20361142 TI - [The heuristics of reaching a diagnosis]. AB - Making a diagnosis in medicine is a complex process in which many cognitive and psychological issues are involved. After the first encounter with the patient, an unconscious process ensues to suspect the presence of a particular disease. Usually, complementary tests are requested to confirm the clinical suspicion. The interpretation of requested tests can be biased by the clinical diagnosis that was considered in the first encounter with the patient. The awareness of these sources of error is essential in the interpretation of the findings that will eventually lead to a final diagnosis. This article discusses some aspects of the heuristics involved in the adjudication of priory probabilities and provides a brief review of current concepts of the reasoning process. PMID- 20361143 TI - [Correlation between depression and family function in older adults from a Family Medicine Unit]. PMID- 20361144 TI - [Synchronous esophagus carcinoma and hypernephroma in a liver transplanted patient]. PMID- 20361145 TI - [Coronary artery origin anomalies. Analysis of 10.000 coronary angiographies]. AB - BACKGROUND: Between 0.3 and 1.3% of coronary arteries, have anomalous origins. Circumflex artery has the higher frequency of anomalies. AIM: To study the frequency of congenital anomalous origins of coronary arteries among adult patients subjected to a coronary angiography. MATERIAL AND METHODS: Analysis of reports of 10,000 coronary angiographies performed in a clinical hospital. Patients with congenital heart disease were excluded. RESULTS: One hundred twenty nine patients (1.3%), aged 59 +/- 12years (70% males) had congenital anomalies in the origin of coronary arteries. The most common anomaly was the origin of right coronary artery from the left coronary sinus in 75%, followed from the origin of circumflex artery from the right side in 20%o. No association between origin anomalies and atherosclerosis or aortic valve disease, was observed. CONCLUSIONS: In this series of patients, origin anomalies of coronary arteries were not associated with aortic valve disease or atherosclerosis, differing from other published reports. Right coronary artery had the highest frequency of anomalies. PMID- 20361147 TI - [Evolution of the availability of physicians in Chile]. AB - There is a significant increase in the physician availability in Chile in the last 15 years, due to the immigration of foreign physicians, but mainly due to the increasing number of graduates from private universities with medical schools. In the last four years, the number of physicians increased from 25.542 to 29.996 and the number of graduates, from 918 to 1.136. These figures show a nearly exponential growth. The number of physicians/number of beneficiaries' ratio increased from 1/630 to 1/569 in the last four years, due to the greater increase in the number of physicians than in the number of inhabitants. The future will show a similar trend in this ratio. The specialist/general practitioner ratio remains practically the same, as the number of physicians/beneficiaries ratio in the public system. The oversupply of physicians should alert authorities about the inconvenience in creating new medical schools and a careful plan of relationship between the offer and demand of medical services. PMID- 20361146 TI - [Frequency of positive anti thyroid peroxidase antibody titers among normal individuals]. AB - BACKGROUND: Anti-thyroid peroxidase antibodies have a pathogenic role in Hashimoto thyroiditis. Between 10 and 19% of individuals without thyroid disease, have positive titers of these antibodies. AIM: To study the frequency of positive titers of anti-thyroid peroxidase antibodies in healthy individuals. MATERIAL AND METHODS: A blood sample, to measure anti-thyroid peroxidase antibodies and thyroid stimulating hormone (TSH) by chemoluminiscense assay, was obtained from 67women and 62 men aged 45 +/- 14years, without a personal or familiar history of thyroid diseases and normal thyroid palpation. The cutoff point of the manufacturer to consider positive a titer of anti-thyroid peroxidase antibodies was set at 35 IU/ml. RESULTS: Twenty-eight women and 28 men had positive antibody titers (43% of the sample). Subjects in the upper tercile of anti-thyroid peroxidase antibody titers had a higher TSH than those in the second tercile, although within normal limits (1.73 +/- 0.74 and 1.37 +/- 0.59 mlU/L, respectively p = 0.02) CONCLUSIONS: Forty three percent of the studied subjects without personal or familial history of thyroid diseases had positive titers of anti-thyroid peroxidase antibodies. Further prospective studies should evaluate whether this observation discloses an increase in thyroid autoimmune disease in a population with increased iodine intake. PMID- 20361148 TI - Leisure time behaviors: prevalence, correlates and associations with overweight in Brazilian adults. A cross-sectional analysis. AB - BACKGROUND: Television viewing (TV viewing) is an important indicator of physical inactivity. AIM: To analyze the prevalence of different leisure time behaviors and TV viewing among healthy adults and their association with overweight. MATERIAL AND METHODS: Cross sectional survey in which 1061 females and 925 males aged 30 years old or more, answered a self administered questionnaire about physical activity Respondents were classified according to frequency participation in sports, walking, cycling and TV viewing. Body mass index (BMI) was derived from self reported weight and height. RESULTS: Less than 30% of individuals participated regularly in sports and less than 15 and 5% reported a high frequency of walking and cycling, respectively. Subjects regularly engaged in sports had a lower BMI. After adjustments, low cycling frequency and high TV viewing were associated with overweight in men and women, respectively. CONCLUSIONS: The prevalence of physical inactivity during leisure time is high among Brazilian adults and associated to obesity. PMID- 20361149 TI - [Public financing of health research in Chile]. AB - BACKGROUND: In Chile, researchers can apply to public research funds through specific research projects and must compete with other professionals of other disciplines. AIM: To perform a critical assessment of the allocation of public funds for health research in Chile by a public institution called CONICYT. MATERIAL AND METHODS: A database was constructed with health projects financed by CONICYT, between 2002 and 2006. Projects were classified (according to their titles) in three methodological categories and nine topics. Age, gender and region where the main researcher is based, were also recorded. RESULTS: 768 research projects were analyzed. Biomedical, clinical and public health research projects accounted for 66, 24 and 10% of allocated funds, respectively. Main researchers were female in 31 % of projects, their mean age was 52 years and 76% worked in the Metropolitan region. CONCLUSIONS: These results show that some objectives of the National Research System lead by CONICYT, such as using research as a tool for regional development and allocating funds for conditions with a large burden, are not been met. PMID- 20361150 TI - [Prevalence of vitamin B-12 deficiency in older adults]. AB - BACKGROUND: There is a correlation between aging and the decrease of plasma levels of vitamin B-12. AIM: To determine the prevalence of vitamin B-12 and folate deficiency and its hematological impact among older adults (AM). MATERIAL AND METHODS: Cross-sectional study, in 1028 subjects aged 65 to 87years, living in community and evaluated between 2005 and 2008. Percentile distribution of vitamin B-12, folate, hemoglobin, packed red cell volume and mean cell volume by gender and age were analyzed. Deficiency was defined as vitamin B-12 levels < 148 pmol/L, marginal deficiency as vitamin B-12 levels < 221 pmol/L, anemia was defined as a hemoglobin < 13 and 12 g/dL among men and women, respectively. RESULTS: The prevalence of vitamin B-12 deficiency was 12% and the figure for marginal deficiency was 25.4%. Males were more affected than females (p < 0.001). The frequency of anemia was 8.6%o, and was higher among women (p = 0.004). CONCLUSIONS: There is a high prevalence of full blown and marginal deficit of vitamin B-12 among the elderly. This deficiency should be considered for correction through public nutrition policies. PMID- 20361151 TI - [Adenocarcinoma of the esophagogastric junction: retrospective analysis of 39 patients]. AB - BACKGROUND: The long-term survival of adenocarcinoma of the esophago-gastric junction is poor and depends on the possibility of performing a complete surgical excision and the absence of lymph node involvement. AIM: To report surgical results and survival of patients with adenocarcinoma of the esophago-gastric junction. MATERIAL AND METHODS: Retrospective review of medical records of patients with adenocarcinoma of the esophago-gastric junction, subjected to a curative surgical procedure between 2000 and 2008. Deaths that occurred within 60 days of the operation were considered operative mortality. Tumor stage was determined using TNM and Siewert pathological classifications. RESULTS: Thirty nine patients aged 40 to 80years (27 men), were operated. According to Siewert classification, seven patients had type I, six type II and 26 type III tumors. Twenty-two patients were subjected to a total gastrectomy with partial excision of distal esophagus and mediastinal reconstruction, 10patients were subjected to a trans-hiatal esophagectomy and seven to a total esophagogastrectomy. According to postoperative staging, five patients were in stage I, 12 in stage II, nine in stage III and 13 in stage IV. Median, three and five year's survival figures were 21.4 months, 33 and 25%, respectively. Lymph node and perineural involvement was associated with a lower survival. Well differentiated and stage I tumors had a better survival. Multivariate analysis showed that the presence of a type III tumor, N3 lymph node involvement and vascular permeation were independent predictors' ofa lower survival. CONCLUSIONS: Among patients with adenocarcinoma of the esophago-gastric junction, type III tumors, lymph node involvement and vascular permeations are associated with a lower survival. PMID- 20361152 TI - [Trends in puberal development of school age children living in the Metropolitan Region of Chile]. AB - BACKGROUND: There is a worldwide tendency towards an earlier appearance of puberal development among children, associated with an increase in weight and height. AIM: To study the trends in puberal development in Chilean school age children, between the years 1986 and 2001 and correlate it with weight and height changes. SUBJECTS AND METHODS: In two representative samples of school age children, collected between years 1985 and 1987 (m-1986) and another between years 2000 and 2002 (m-2001), girls between 7 and 15years (958 and 935, respectively) and boys between 9 and 15 years (842 and 870 respectively), were selected. Breast development (B) in females and genital development (G) in males were classified according to Tanner stages. Weight, height, body mass index (BMI) and nutritional status (according to Centers for Disease Control/ National Center for Health Statistics (CDC/NCHS) standards) were assessed. RESULTS: The prevalence of obesity increased four fold between 1986 and 2001. The 2001 generation had a significantly higher degree of puberal development than their counterparts studied in 1986. Compared to m-1986, m-2001 subjects had a lower mean age at puberal development stage two and three, but no differences at puberal stages 4 and 5. BMI of m-2001 subjects was significantly higher than that of m-1986 subjects at all puberal stages. The m-2001 males showed highest stature than m-1986 in all puberal stage, however, in females there is no difference in height between m-2001 and m-1986. CONCLUSIONS: The highest BMI observed in the cohort of 2001, could be facilitating an earlier puberal development and ethnic factors could explain the sexual dimorphism in stature. PMID- 20361153 TI - [Distal intestinal obstruction syndrome: report of two cases with cystic fibrosis]. AB - Distal Intestinal Obstruction Syndrome (DIOS) has a 16% incidence among patients with Cystic Fibrosis (CF). It is characterized by an intestinal obstruction secondary to fecal impaction in distal ileum or cecum. We report two adult patients with DIOS. A female with CF and subjected to lung transplantation at the age of 13 years old. Five years later, she consulted for an intestinal obstruction. She was treated conservatively with a good clinical evolution. She had a new episode of DIOS eight months later that was also treated conservatively. A 31 year-old mole, subjected to bilateral lung transplantation nine years before, that was admitted to the hospital for a bronchiolitis. Three days after admission he started with an intestinal obstruction that was diagnosed as a DIOS. He was managed conservatively with a good clinical response. PMID- 20361154 TI - [Stewart-Treves syndrome: report of one case]. AB - Angiosarcomas are malignant tumors derived from the endothelium of blood vessel (hemangiosarcomas) or lymph vessels (lymphangiosarcomas). Lymph edema of the limbs is considered secondary when extrinsic injuries are observed and primary when these injuries are not present. Stewart-Treves syndrome or a Lymphangiosarcoma, developed over a chronic lymph edema, is a rare complication described in mastectomized patients but it can be observed in lymph edemas located elsewhere. It appears as nodular skin lesions that grow, multiply quickly and frequently metastasize. We report a 40-year-old mole with an angiosarcoma associated with primary chronic lower limb lymph edema. The patient consulted for a history of weight loss and malaise and appearance of violaceous lesions over the zone of lymph edema and inguinal lymph node involvement. A CT scan showed bilateral lung lesions and enlargement of inguinal and iliac lymph nodes. A biopsy of one of the skin lesions disclosed an angiosarcoma, diagnosis that was confirmed with immuno-histochemistry Chemotherapy was started but the patient died five months after the diagnosis. PMID- 20361155 TI - [Esophageal melanoma: report of two cases]. AB - Esophageal melanomas correspond to 0.1 to 0.2% of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study ofthe biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relapse. PMID- 20361156 TI - [Pulmonary artery aneurism in a patient with Behcet disease. Report of one case]. AB - Behcet disease is a systemic disease with diverse clinical symptoms which vary according to the organs and systems involved. Typically, patients have oral and genital ulcers and episodic ocular involvement with periods of clinical improvement. We report an 18-year-old mole presenting with chest pain and hemoptysis and a history of ulcers in the oral cavity and scrotum. A chest CAT scan showed a mass located adjacent to the heart that a pulmonary arteriography defined as a left pulmonary artery aneurism. The patient was operated, excising left inferior pulmonary lobe. Due to skin and ocular involvement, the patient complied with criteria for Behcet disease. Immunosuppressive treatment with prednisone and azathioprine was started and the patient was discharged from the hospital. PMID- 20361157 TI - [Confirmatory analysis for the test AEQ-III in Bucaramanga, Colombia.]. AB - BACKGROUND: The Alcohol Expectancy Questionnaire-III (AEQ-III) test evaluates positive expectations towards alcohol consumption. AIM: To perform a confirmatory factorial analysis of the AEQ-III test. MATERIAL AND METHODS: During 2006-2008, 1199 adults between 18 and 60years old (588 males) answered a survey that included socio-economic variables and the AEQ-III test to determine alcohol consumption and its consequences. A factorial analysis was performed and the goodness off it of the final model was assessed. RESULTS: "Increase in expressivity and sexuality", "decrease in physical tension", "lack of inhibition and feelings of power" and "decrease in psychological tension" were the four confirmed dimensions. This model differs of others applied in the region, has 22 variables and adjusts well. Values for median quadratic approximation error, Tucker- Lewis Index, normal adjustment index and goodness off it were 0.07, 0.93 and 0.92, respectively. The variance explained by the model increased from 62% in the exploratory to 76% in the confirmatory analysis. Infernal consistency in the exploratory and confirmatory models was 0.85 and 0.87. CONCLUSIONS: Two confirmed dimensions correspond to group behaviors and the others, to individual behaviors. All indices of relevance of grouping variables, goodness off it and parsimony were maintained and even improved and are generally optimal. PMID- 20361158 TI - [Syndecans in the diagnosis and prognosis of prostate cancer]. AB - Syndecans, a family of heparan sulphate proteoglycans that are present in the cellsurface are involved in the control o fcel lproliferation, apoptosis and transfor-mation. Syndecans 1 and 2 have a central role in processes such as position control, invasion, angiogenesis and metastases ofseveral types of cancer The expression of Syndecan 1 in epithelial cells, decreases when cells are transformed and acquire invasive properties. This decreased expression is associated to a bad prognosis. Syndecan 2, originally described in mesenchymal cells, favors cell apoptosis, increa-ses angiogenesis and controls the death of cancer cells subjected to chemotherapy Both syndecans are present in basal and epithelial cells of prostate cancer Their lower expression is associated to more undifferentiated tumors. Disturbances in the expression and subcellular location of syndecans predict the relapse of localized tumors. Syndecans 1 and 2 can be considered tumor suppression genes and can be targetsfor new treatments. The detection of circulating fragments of these molecules could be useful for the early detection of prostate cancer. PMID- 20361159 TI - [Femoroacetabular impingement as a cause of inguinal pain]. AB - Femoro-acetabular impingement is an anatomical disturbance of the hip, caused by a deformity of the acetabulum, femur or both that causes an abnormal contact between both structures during certain movements. Its prevalence is 10 to 15% and causes chronic inguinal pain. It can be confused with several other causes of inguinal pain such as hernias, facet syndromes, a renal colic, etc. Patients with this condition are usually young individuals with inguinal pain that may appear after a minor trauma. During examination, pain may be elicited by infernal rotation and abduction movements of hip, flexed in 90 degrees . Plain hip X ray is the most commonly used diagnostic method. Non-steroidal anti-inflammatory drugs and physical therapy can be used to alleviate pain, but the definitive treatment is surgical. PMID- 20361160 TI - [Active and refractory ulcerative proctitis: an update]. AB - Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology that affects a variable length of the colon, starting from the rectum. When the disease is confined to the rectum is called ulcerative proctitis (UP). Several studies have unsuccessfully attempted to determine the factors that determine the extent of involvement. The goals of therapy in UP are to induce and maintain remission of symptoms and disease. Topical treatment with 5-aminosalicylates (5 ASA) is the treatment of choice to induce remission. In the maintenance phase, long-term follow up studies suggest that treatment with 5-ASA is better than placebo, to maintain the disease inactive. For those patients that do not respond to treatment with topical 5-ASA or have a moderate to severe disease, there are additional therapies such as oral 5-ASA, topical or systemic corticosteroids, immunomodulators, biological therapies (Infliximab) and cyclosporine. Surgery is seldom needed. PMID- 20361161 TI - [The influence of madness in the literary production of Gerard de Nerval]. AB - Gerard de Nerval was a French writer, poet and essayist, precursor of surrealism that used for the first time this word in literature and influenced many modern writers. Since the age of 32, Nerval had recurrent psychotic episodes mixed with a severe depression, leading to many hospitalizations, and finally to his death. This mental disease clearly influenced his works and provided originality to his prose and poetry. However no clear explanation has ever been given to his mental disorder. We analyzed the clinical data available from his own works and the opinion of his close friends and postulate the hypothesis that Nerval had a mood disorder. PMID- 20361162 TI - [Jean-Paul Marat: physician, scientist and revolutionary]. AB - Physician, scientist and revolutionary are the biographical aspects that had better summarize the life of Jean-Paul Marat (1743-1793). Due to the role that he played during the French Revolution, his work as a physician and scientist, prior to the events of l789, was forgotten. Marat made important contributions in the area of optics and electricity reflected in numerous publications, as well as translating Newton's Opticks (1787). Well known for his radical and aggressive ideas, his political vocation led him to embrace the revolutionary cause after the events of the Bastille. His figure was not indifferent to his contemporaries; although considered a hero by the poorest citizens, aristocrats and bourgeois considered him a cruel extremist. During the last years of his life, he suffered a cutaneous disease, the diagnosis of which is still a matter of controversy. Proposed diagnoses include eczema, seborrheic dermatitis, scabies and dermatitis herpetica, among others. Marat was assassinated by Charlotte Corday in 1793, becoming a martyr for some segments of the society that worshiped his memory. He was a man with a complex and curious personality whose figure and legacy are still a matter of discussion. PMID- 20361163 TI - [Genetic tests: definition, methods, validity and clinical utility]. AB - The knowledge of the human genome has led to an explosion of available genetic tests for clinical use. The methodologies used in these tests vary widely, allowing the study from chromosomes to the analysis of a single nucleotide. Prior to its use in the clinical setting, these tests should have an evaluation that includes analytical and clinical validation and determination of the clinical utility, as any other tests, including requirements for quality assurance. Recently, the CDC (Centers for Disease Control and Prevention, USA) published a guideline for Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions, covering the pre-analytical, analytical and post-analytical phases of the tests. The document covers the importance of proper selection of tests, the availability of information on the performance of the techniques used, the quality control practices, the training of personnel involved and the report of results, to allow the adequate interpretation, including sensitivity and specificity. Considering that recent advances in genetics have changed and will continue to affect clinical practice, genetic tests must meet quality and safety requirements to enable optimal use of them. PMID- 20361164 TI - [Position statement of the Chilean Academy of Medicine, in reaction to a law passed by the Government and the Parliament, that establishes new regulations with regards to a temporary recognition of specialists and subspecialists]. PMID- 20361166 TI - [Duty hours requirements in Residency Programs: a still debatable need]. PMID- 20361167 TI - Alefacept treatment for chronic plaque psoriasis. AB - Biologic agents were introduced during the past decade as a new class of treatments for chronic psoriasis. These agents provide therapeutic alternatives to traditional topical and systemic therapies. Alefacept, the first such biologic agent, was approved by the US FDA in January 2003 for the treatment of chronic plaque psoriasis. This review will discuss data from clinical trials that have provided new insights into the efficacy, safety, and cost effectiveness of alefacept as a treatment for psoriasis. PMID- 20361168 TI - What is needed for a sunscreen to provide complete protection. AB - Human skin is increasingly exposed to sunlight. In order to achieve complete protection against the cumulative detrimental effects from sun exposure, topical strategies must shield against the range of solar wavelengths that can damage the skin. Importantly, the harm sustained by the skin is not limited to that caused by the ultraviolet (UV) portion of the light spectrum, but also includes the adverse effects inflicted by near infrared energy. Consequently, in an attempt to provide the necessary broad spectrum coverage, innovative research continues through the exploration of new compounds and novel combinations of chemical and physical UV filters with molecules that are capable of interfering with and/or preventing the deleterious effects of infrared A (IRA) radiation. Existing examples of infrared-protective active agents include mitochondrially targeted antioxidants of synthetic or natural origin. PMID- 20361169 TI - Pruritus: control of itch in patients undergoing dialysis. AB - Chronic kidney disease (CKD)-associated pruritus is a significant clinical symptom affecting more than 50% of patients on hemodialysis. Restricted by the availability of effective therapeutic options, the management of CKD-associated pruritus remains a treatment challenge. Evaluating research in this area is difficult, as most studies are not comparable due to differing methodologies and study designs, limited number of patients, and the lack of standardized measures. The most frequently used therapy is UVB phototherapy, eliciting favorable responses in most patients. Newer approaches, such as treatment with the m-opiod receptor antagonist, naltrexone, have yielded conflicting results. The use of the k-opioid-receptor-agonist, nalfurafine, appears to be partially effective in relieving CKD-associated pruritus, as shown by a meta-analysis of 2 clinical trials. Promising results have been obtained by treatment with the anticonvulsant gabapentin. CKD-associated pruritus is thought to be mediated by a proinflammatory state, which explains why immunomodulating drugs (e.g., thalidomide, tacrolimus, and pentoxiphylline) are effective in some patients. Treatment of CKD-associated pruritus should be undertaken according to individual benefit-risk ratio assessments. PMID- 20361170 TI - Drug treatments for skin disease introduced in 2009. PMID- 20361171 TI - Does diet really affect acne? AB - Acne vulgaris has anecdotally been attributed to diet by individuals affected by this skin condition. In a 2009 systematic literature review of 21 observational studies and 6 clinical trials, the association between acne and diet was evaluated. Observational studies, including 2 large controlled prospective trials, reported that cow's milk intake increased acne prevalence and severity. Furthermore, prospective studies, including randomized controlled trials, demonstrated a positive association between a high-glycemic-load diet, hormonal mediators, and acne risk. Based on these findings, there exists convincing data supporting the role of dairy products and high-glycemic-index foods in influencing hormonal and inflammatory factors, which can increase acne prevalence and severity. Studies have been inconclusive regarding the association between acne and other foods. PMID- 20361172 TI - Current concepts in laser tattoo removal. AB - Today, more than 10% of the Western population has at least 1 tattoo, with prevalence of up to one-fourth in the cohort younger than 30 years of age. Many of these individuals come to regret their decision within months due to several reasons, often socially-related, and seek medical treatment. The discovery of selective photothermolysis has enabled the targeted destruction of tattoo pigments with only minimal damage to the surrounding tissue and limited risk of adverse effects, which contrasts previously used nonspecific methods. This treatment modality requires laser pulses of short durations (nanoseconds) and high intensities. However, the inappropriate use of laser parameters, such as inadequate pulse duration, can unnecessarily increase the incidence of permanent adverse effects. This article provides an overview of applicable laser systems and therapeutic strategies for optimized tattoo removal. PMID- 20361173 TI - [Confocal laser scanning microscopy]. AB - The diagnosis of skin diseases relies strongly on clinical inspection and the use of invasive diagnostic procedures. Routine histology requires the removal of tissue for microscopic evaluation, which is associated with pain, and risk of infection as well as scar formation. In the past 15 years a number of non invasive diagnostic devices have been evaluated for use in clinical and investigative dermatology. A number of studies have assessed the applicability of confocal laser scanning microscopy (LSM) as an optical diagnostic device in dermatology. By correlating LSM images with established features of routine histology, it was possible to define diagnostic LSM parameters for a number of selected skin diseases. Present data supports the use of LSM as an adjunct diagnostic device for selected skin conditions in clinical as well as investigative dermatology. Since LSM examinations may repeatedly be performed, LSM is particularly suited for evaluation of dynamic, neoplastic and regenerative skin processes as well as the definition of disease extent and response to therapy. PMID- 20361174 TI - [Forensic psychiatry and behavioural analysis]. AB - A case report shows that a patient could make a progress in his therapy with the help of professional behavioural analysis after a 14-year period of stagnating forensic therapy. The method of behavioural analysis represents a criminalistic tool to reconstruct and to analyse an offence on the basis of objective data. Nowadays this method is also used successfully in individual cases in the field of forensic psychiatry. The article shows and discusses the methodology and the current use of behavioural analysis in forensic psychiatry. CONCLUSION: professional behavioural analysis of offences of certain forensic patients provides an additional benefit for their therapy and their risk assessment. This kind of approach should be intensified by increasing cooperation with behavioural analysis units and by further training for forensic therapists. PMID- 20361175 TI - [Bipolar affective disorder]. PMID- 20361176 TI - [Mountain biking : Breezy ups and traumatic downs]. AB - For more than two decades the popularity of mountain biking as a national pastime as well as a competitive sport has been undiminished. However, its related risks are not monitored as closely as those, for example, of skiing. The injuries caused by mountain biking are specific and cannot be compared with those caused by other cycling sports. This is due not only to the characteristics of the terrain but also to the readiness to assume a higher risk compared to cycle racing.The particular value of radiology is in the acute trauma setting. Most often musculoskeletal lesions must be examined and digital radiography and MRI are the most useful techniques. Severe trauma of the cranium, face, spine, thorax and abdomen are primarily evaluated with CT, particularly in dedicated trauma centers. Therefore, radiology can play a role in the rapid diagnosis and optimal treatment of the trauma-related injuries of mountain biking. Thus, the unnecessarily high economical damage associated with mountain biking can be avoided. PMID- 20361177 TI - Beta cell coupling and connexin expression change during the functional maturation of rat pancreatic islets. AB - AIMS/HYPOTHESIS: Cell-cell coupling mediated by gap junctions formed from connexin (CX) contributes to the control of insulin secretion in the endocrine pancreas. We investigated the cellular production and localisation of CX36 and CX43, and gap junction-mediated beta cell coupling in pancreatic islets from rats of different ages, displaying different degrees of maturation of insulin secretion. METHODS: The presence and distribution of islet connexins were assessed by immunoblotting and immunofluorescence. The expression of connexin genes was evaluated by RT-PCR and quantitative real-time PCR. The ultrastructure of gap junctions and the function of connexin channels were assessed by freeze fracture electron microscopy and tracer microinjection, respectively. RESULTS: Young and adult beta cells, which respond to glucose, expressed significantly higher levels of Cx36 (also known as Gjd2) than fetal and newborn beta cells, which respond poorly to the sugar. Accordingly, adult beta cells also showed a significantly higher membrane density of gap junctions and greater intercellular exchange of ethidium bromide than newborn beta cells. Cx43 (also known as Gja1) was not expressed by beta cells, but was located in various cell types at the periphery of fetal and newborn islets. CONCLUSIONS/INTERPRETATION: These findings show that the pattern of connexins, gap junction membrane density and coupling changes in islets during the functional maturation of beta cells. PMID- 20361179 TI - Interaction proteomics of synapse protein complexes. AB - The brain integrates complex types of information, and executes a wide range of physiological and behavioral processes. Trillions of tiny organelles, the synapses, are central to neuronal communication and information processing in the brain. Synaptic transmission involves an intricate network of synaptic proteins that forms the molecular machinery underlying transmitter release, activation, and modulation of transmitter receptors and signal transduction cascades. These processes are dynamically regulated and underlie neuroplasticity, crucial to learning and memory formation. In recent years, interaction proteomics has increasingly been used to elucidate the constituents of synaptic protein complexes. Unlike classic hypothesis-based assays, interaction proteomics detects both known and novel interactors without bias. In this trend article, we focus on the technical aspects of recent proteomics to identify synapse protein complexes, and the complementary methods used to verify the protein-protein interaction. Moreover, we discuss the experimental feasibility of performing global analysis of the synapse protein interactome. PMID- 20361180 TI - Use of proficiency testing materials for the calculation of detection and quantification limits in the analysis of organochlorine compounds in human serum. AB - A method for the calculation of the limits of detection (LD) and quantification (LQ) for the analysis of organochlorine compounds in serum is described. The method is based on the analysis of proficiency testing materials, an external quality assessment for selected pollutants, and the study of the signal/noise ratio of chromatograms obtained from GC-ECD injection. This method provides representative results for matrix effects, instrumental variability and extraction recoveries in the analysis of serum samples. PMID- 20361183 TI - Mitochondrial creatine kinase interaction with cardiolipin-containing biomimetic membranes is a two-step process involving adsorption and insertion. AB - Mitochondrial creatine kinase (mtCK) binding to the mitochondrial inner membrane largely determines its biological functions in cellular energy homeostasis, mitochondrial physiology, and dynamics. The membrane binding mechanism is, however, not completely understood. Recent data suggest that a hydrophobic component is involved in mtCK binding to cardiolipin at the outer face of the inner mitochondrial membrane, in addition to the well known electrostatically driven process. In this manuscript, using an electrochemical method derived from alternating current polarography for differential capacity measurements, we distinctly reveal that protein-cardiolipin interaction has a two-step mechanism. For short incubation time, protein adsorption to the phospholipid charged headgroup was the only process detected, whereas on a longer time scale evidence of protein insertion was observed. PMID- 20361178 TI - Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. AB - Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients. PMID- 20361184 TI - New strategies for the manipulation of adaptive immune responses. AB - The maintenance of peripheral tolerance is largely based on thymus-derived CD4(+)CD25(+) naturally occurring regulatory T cells (Tregs). While on the one hand being indispensable for the perpetuation of tolerance to self-antigens, the immune suppressive properties of Tregs contribute to cancer pathogenesis and progression. Thus, modulation of Treg function represents a promising strategy to support tumor eradication in immunotherapy of cancer. Here, we discuss potential therapeutic applications of our observation that Tregs contain high concentrations of the second messenger cyclic adenosine monophosphate, which is transferred from Tregs via gap junctions to suppress the function of T cells and dendritic cells. PMID- 20361185 TI - Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. AB - Adenovirus serotype 5 (Ad5) has been widely used in clinical trials because it expresses inserted transgenes robustly and augments the innate immune response. Strategies to improve Ad5 vectors that can circumvent Ad5 immunity have become a critical issue, especially for use as a cancer immunotherapeutic in which repeated immunization is required. In this study, we constructed a novel Ad5 vector with unique deletions of the viral DNA polymerase and the pre-terminal protein region (Ad5 [E1-, E2b-]). This vector contains the carcinoembryonic antigen (CEA) gene insert and is designed to induce cell-mediated immunity (CMI) against the tumor-associated target. The CEA immunogenicity and in vivo anti tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre immunized mice. We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA. Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice. These results demonstrate that Ad5 [E1 , E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity. Multiple re immunizations using the same vector platform are now possible with the novel Ad5 [E1-, E2b-] platform. PMID- 20361186 TI - Cytotherapy of osteonecrosis of the femoral head: a mini review. AB - The pathogenesis and aetiology of nontraumatic osteonecrosis of the femoral head has not been revealed completely. However, with advances in stem cell research and regenerative medicine, it is believed that the onset of osteonecrosis of the femoral head probably has a cellular origin, and the possible therapy of osteonecrosis of the femoral head based on cytotherapy has great potential. In this review, the aetiology of osteonecrosis of the femoral head, animal experiments and clinical applications of cytotherapy are summarized and analysed. Current problems and future challenges are discussed. PMID- 20361187 TI - Upper body reshaping for the woman with massive weight loss: an algorithmic approach. AB - BACKGROUND: Body contouring after massive weight loss represents a rather new surgical field. Many areas of the body are affected such as the back, the upper arms, and the breasts in the upper body. Combining more than one such area in a single operative step can yield many advantages. The author proposes a single step approach to the upper body of the woman with massive weight loss and offers an algorithm to simplify the operative plan. METHODS: Based on the characteristics of the individual, each adjacent region is analyzed for the potential of surgical improvement. Several lifting techniques can be used to restore the shape of each region. The breast represents a rather unique entity in which three basic types can be recognized. Accordingly, a surgical plan is formulated and discussed with the patient. RESULTS: The presented algorithm was used successfully for 17 consecutive women after massive weight loss. Although the time for these combined operations was increased, patient safety was not reduced nor were the number of complications increased compared with multiple smaller operations. The overall treatment plan for this patient group was greatly enhanced and simplified with this approach and resulted in great patient satisfaction. CONCLUSION: Body contouring after massive weight loss presents a steadily increasing surgical field. Typically, multiple operative steps are required to achieve the patient's ultimate goal. The author offers a surgical algorithm that aids in the operative planning for the upper body of such patients that simplifies this operation and yields great patient satisfaction. PMID- 20361188 TI - Acquired KRAS mutations during progression of colorectal cancer metastases: possible implications for therapy and prognosis. AB - PURPOSE: Documentation of a wild-type (wt) KRAS gene in tumor has become mandatory for the prescription of anti-EGFR monoclonal antibodies in patients with colorectal cancer (CRC). Acquired KRAS mutations have seldom been reported in metastases from wt KRAS primary CRC. We report the first case of multiple KRAS mutations acquired during the metastatic phase of CRC, and retrospectively reviewed all patients with CRC, in whom KRAS was analyzed in at least two tumor samples from distinct lesions. METHODS: Genomic DNA purified from paraffin embedded tissues was used after histological quantification of tumor tissue. The seven KRAS mutations located within codons 12 and 13 were screened using the allelic discrimination assay. RESULTS: A 35-year-old woman with CRC liver metastasis, resistant to all conventional cytotoxic agents, experienced for the first time significant tumor shrinkage while cetuximab was added, allowing hepatic resection. Further liver relapse occurred on cetuximab, but a new hepatic resection was attempted. No mutation in KRAS was detected in the primary colon tumor or in synchronous liver metastases. In contrast, in metachronous liver metastasis samples, two distinct mutations at codon 13 and 12 were detected. No acquired mutations were found in all the other 12 CRC cases with at least two serially performed KRAS analyses. CONCLUSIONS: Our findings suggest that late switch in KRAS mutational status could occur more frequently than currently recognized and account for acquired resistance to anti-EGFR therapies. Prospective studies are warranted to better estimate the incidence of change in KRAS mutational status and assess their clinical relevance. PMID- 20361189 TI - Inhibitory activity by barley coffee components towards Streptococcus mutans biofilm. AB - It was shown that barley coffee (BC) interferes with Streptococcus mutans adsorption to hydroxyapatite. After BC component fractionation by dialysis and gel filtration chromatography (GFC), it was found that the low molecular mass (<1,000 Da) fraction (LMM fraction) containing polyphenols, zinc and fluoride ions and, above all, a high molecular mass (HMM > 1,000 kDa) melanoidin fraction display strong anti-adhesive properties towards S. mutans. In this study, we have further examined the potential of BC, BC LMM fraction and BC HMM melanoidin fraction as caries controlling agents by evaluating their anti-biofilm activity.The effects of BC and BC fractions on biofilm formation by S. mutans ATCC 25175 and its detachment from pre-developed biofilms were evaluated by microtiter plate assay. It was found that BC and its fractions, at concentrations ranging from 60 to 15 mg ml(-1) that are devoid of antimicrobial activity, inhibited S. mutans biofilm formation. An increase of S. mutans ATCC 25175 detachment from 24 h developed biofilm was observed at the highest tested concentrations. Interestingly, BC and BC fractions also showed anti-biofilm activity towards a variety of S. mutans clinical strains isolated from saliva, plaque and caries lesions of adult donors. In general, the HMM melanoidin fraction was more active than the LMM fraction. These findings, classifying BC LMM fraction and BC HMM melanoidin fractions as natural anti-biofilm agents, represent the basis for studying their possible use as anti-caries agents. PMID- 20361190 TI - Flow cytometry approach study of Enterococcus faecalis vancomycin resistance by detection of Vancomycin@FL binding to the bacterial cells. AB - We studied the usefulness of flow cytometry for detection of vancomycin resistance in Enterococcus faecalis by direct binding of commercially available fluorescent vancomycin to cells obtained from culture. The cells were stained with Vancomycin@FL, sonicated and additionally stained with propidium iodide (PI). Regarding to inductive mechanism of vanA-mediated vancomycin resistance, resistant reference strain was also pre-incubated with vancomycin. PI staining divided cells into two subpopulations. There were significantly lower mean FL1 fluorescence values and mean fluorescence per particle (FL1/FSC) in reference vancomycin-resistant strain than in reference and clinical strains sensitive to this antibiotic. Pre-incubation with vancomycin of vancomycin resistant enterococci strain modified Vancomycin@FL binding, however, cells remained easy to differ. We have demonstrated new, quick and sensitive method for detection of vancomycin resistant strains of E. faecalis. The study proved possibility of detection of vancomycin resistance caused by presence of vanA gene by staining cells with Vancomycin@FL. Flow cytometry approach study of E. faecalis vancomycin resistance by detection of Vancomycin@FL binding to the bacterial cells. PMID- 20361191 TI - Protein profile analysis of salt-responsive proteins in leaves and roots in two cultivars of creeping bentgrass differing in salinity tolerance. AB - Knowledge of stress-responsive proteins is critical for further understanding the molecular mechanisms of stress tolerance. The objectives of this study were to establish a proteomic map for a perennial grass species, creeping bentgrass (A. stolonifera L.), and to identify differentially expressed, salt-responsive proteins in two cultivars differing in salinity tolerance. Plants of two cultivars ('Penncross' and 'Penn-A4') were irrigated daily with water (control) or NaCl solution to induce salinity stress in a growth chamber. Salinity stress was obtained by adding NaCl solution of 2, 4, 6, and 8 dS m(-1) in the soil daily for 2-day intervals at each concentration, and then by watering soil with 10 dS m(-1) solution daily for 28 days. For proteomic map, using two-dimensional electrophoresis (2-DE), approximately 420 and 300 protein spots were detected in leaves and roots, respectively. A total of 148 leaf protein spots and 40 root protein spots were excised from the 2-DE gels and subjected to mass spectrometry analysis. In total, 106 leaf protein spots and 24 root protein spots were successfully identified. Leaves had more salt-responsive proteins than roots in both cultivars. The superior salt tolerance in 'Penn-A4', indicated by shoot extension rate, relative water content, and cell membrane stability during the 28 day salinity stress could be mainly associated with its higher level of vacuolar H(+)-ATPase in roots and UDP-sulfoquinovose synthase, methionine synthase, and glucan exohydrolase in leaves, as well as increased accumulation of catalase and glutathione S-transferase in leaves. Our results suggest that salinity tolerance in creeping bentgrass could be in part controlled by an alteration of ion transport through vacuolar H(+)-ATPase in roots, maintenance of the functionality and integrity of thylakoid membranes, sustained polyamine biosynthesis, and by the activation of cell wall loosening proteins and antioxidant defense mechanisms. PMID- 20361192 TI - Interaction of liquid epicuticular hydrocarbons and tarsal adhesive secretion in Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae). AB - Species of various insect orders possess specialised tarsal adhesive structures covered by a thin liquid film, which is deposited in the form of footprints. This adhesive liquid has been suggested to be chemically and physiologically related to the epicuticular lipid layer, which naturally covers the body of insects and acts as the prime barrier to environmental stresses, such as desiccation. The functional efficiency of the layer, however, is jeopardised by partial melting that may occur at physiological temperatures. In this study, light microscopic images of elytral prints show that the epicuticular lipid layer of the Colorado potato beetle Leptinotarsa decemlineata actually is partially liquid and chemical investigations reveal the high similarity of the epicuticular hydrocarbon pattern and the tarsal liquid. By means of chemical manipulation of the surface hydrocarbon composition of live beetles, the substance exchange between their tarsal adhesive hairs and the body surface is monitored. Histological sections of L. decemlineata tarsi, furthermore, reveal glandular cells connected to individual adhesive setae and departing from these results, an idea of a general mechanism of tarsal secretion is developed and discussed in a functional ecological context. PMID- 20361193 TI - Quadrupedal locomotor performance in two species of arboreal squirrels: predicting energy savings of gliding. AB - Gliding allows mammals to exploit canopy habitats of old-growth forests possibly as a means to save energy. To assess costs of quadrupedal locomotion for a gliding arboreal mammal, we used open-flow respirometry and a variable-speed treadmill to measure oxygen consumption and to calculate cost of transport, excess exercise oxygen consumption, and excess post-exercise oxygen consumption for nine northern flying squirrels (Glaucomys sabrinus) and four fox squirrels (Sciurus niger). Our results indicate that oxygen consumption during exercise by flying squirrels was 1.26-1.65 times higher than predicted based on body mass, and exponentially increased with velocity (from 0.84 +/- 0.03 ml O(2) kg(-1) s( 1) at 0.40 m s(-1) to 1.55 +/- 0.03 ml O(2) kg(-1) s(-1) at 0.67 m s(-1)). Also, cost of transport in flying squirrels increased with velocity, although excess exercise oxygen consumption and excess post-exercise oxygen consumption did not. In contrast, oxygen consumption during exercise for fox squirrels was similar to predicted, varying from 0.51 (+/-0.02) ml O(2) kg(-1) s(-1) at 0.63 m s(-1) to 0.54 (+/-0.03) ml O(2) kg(-1) s(-1) at 1.25 m s(-1). In addition, the cost of transport for fox squirrels decreased with velocity, while excess exercise oxygen consumption and excess post-exercise oxygen consumption did not. Collectively, these observations suggest that unlike fox squirrels, flying squirrels are poorly adapted to prolonged bouts of quadrupedal locomotion. The evolution of skeletal adaptations to climbing, leaping, and landing and the development of a gliding membrane likely has increased the cost of quadrupedal locomotion by >50% while resulting in energy savings during gliding and reduction in travel time between foraging patches. PMID- 20361194 TI - Acquisition of Ca(2+) and HCO3(-)/CO3(2-) for shell formation in embryos of the common pond snail Lymnaea stagnalis. AB - Embryos of the freshwater common pond snail Lymnaea stagnalis develop to hatch within 10 days under control conditions (22 degrees C, Miami-Dade tap water) and this development is impaired by removal of ambient calcium. In contrast, embryos did not exhibit dependence upon an ambient HCO(3)(-)/CO(3)(2-) source, developing and hatching in HCO(3)(-)/CO(3)(2-)-free water at rates comparable to controls. Post-metamorphic, shell-laying embryos exhibited a significant saturation-type calcium uptake as a function of increasing ambient calcium concentration. However, changes in ambient bicarbonate concentration did not influence calcium or apparent titratable alkalinity uptake. There was a distinct shift from no significant flux in pre-metamorphic embryos to net uptake of calcium in post metamorphic stages as indicated by an increased uptake from the micro-environment surrounding the egg mass and increased net uptake in 24-h, whole egg mass flux measurements. Furthermore, HCO(3)(-)/CO(3)(2-) acquisition as measured by titratable alkalinity flux is at least partially attributable to an endogenous carbonate source that is associated with acid extrusion. Thus, calcium requirements for embryonic shell formation are met via uptake but HCO(3)( )/CO(3)(2-), which is also necessary for shell formation is acquired in part from endogenous sources with no detectable correlation to ambient HCO(3)(-)/CO(3)(2-) availability. PMID- 20361195 TI - [Physical activity during the transition period between occupation and retirement]. AB - BACKGROUND: During the transition period between occupation and retirement, different mental challenges may arise as a consequence of the numerous changes and necessary reorientation to the following phase of life. Personal well-being is a precondition to cope with these challenges. METHODS: Interviews with physically active people in the transition period between occupation and retirement, concerning the importance of physical activity in coping with mental challenges, were conducted. RESULTS: Physical activity is meant to affect well being and the physical condition in a positive way. In addition, it should foster social contacts and make it easier to manage everyday life. Moreover, it is a measure of personal success during advanced age. CONCLUSION: Because of its influence on various physical, mental, and social aspects, physical activity can help a person to cope with mental challenges in the transition period between occupation and retirement. PMID- 20361196 TI - Unrecognized secondary causes of hypertension in patients with hypertensive urgency/emergency: prevalence and co-prevalence. AB - BACKGROUND: Hypertensive urgency/emergency occurs frequently, yet no prospective data on common secondary causes, including sleep apnea (SA), renal artery stenosis (RAS), and hyperaldosteronism, are available. METHODS: Patients presenting to the emergency room for over 1 year with systolic blood pressure > or =180 mmHg and/or diastolic blood pressure > or =100 mmHg and typical symptoms were included. RAS was diagnosed by direct duplex/Doppler ultrasound of the renal artery, resistance index, and imaging. The aldosterone/renin ratio (ARR) was determined from morning blood samples taken with the patients supine after > or =2 h of rest. A positive ARR (>50) was followed by saline infusion to exclude primary hyperaldosteronism. SA was evaluated by nasal breathing flow screening; when positive [apnea/hypopnea index (AHI) >5/h], complete polysomnography was performed. RESULTS: Of 161 patients (age, 66.0 +/- 13.1 years; BMI, 28.6 +/- 5.1 kg), 131 had previously identified hypertension (duration, 12.7 +/- 11.5 years; 1.9 +/- 1.5 antihypertensive medications). SA was found in 114 (70.8%) patients [18% mild (AHI: 5-15/h), 26.8% moderate (15.1-30/h), and 24.2% severe (>30/h)]. Aldosterone levels exceeded 160 pg/ml in 22 of 23 patients with hyperaldosteronism; 4 had primary and 12 had secondary hyperaldosteronism. Thirteen (8.1%) patients had RAS. Three secondary causes were found in 1 patient (0.6%), > or =2 in 25 (15.5%), and > or =1 in 124 patients (77.0%). Of 150 detected secondary causes, only 5 were recognized previously. CONCLUSIONS: Secondary causes of hypertension are common and predominantly unrecognized in patients with hypertensive urgency/emergency. Co-prevalence of secondary causes occurs in about 15% and should be considered before therapeutic intervention. PMID- 20361197 TI - CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function. AB - Inhibition of the cannabinoid receptor CB(1) (CB(1)-R) exerts numerous positive cardiovascular effects such as modulation of blood pressure, insulin sensitivity and serum lipid concentrations. However, direct vascular effects of CB(1)-R inhibition remain unclear. CB(1)-R expression was validated in vascular smooth muscle cells (VSMCs) and aortic tissue of mice. Apolipoprotein E-deficient (ApoE /-) mice were treated with cholesterol-rich diet and the selective CB(1)-R antagonist rimonabant or vehicle for 7 weeks. CB(1)-R inhibition had no effect on atherosclerotic plaque development, collagen content and macrophage infiltration but led to improved aortic endothelium-dependent vasodilation and decreased aortic reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of cultured VSMC with rimonabant resulted in reduced angiotensin II mediated but not basal ROS production and NADPH oxidase activity. CB(1)-R inhibition with rimonabant and AM251 led to down-regulation of angiotensin II type 1 receptor (AT1-R) expression, whereas stimulation with the CB(1)-R agonist CP 55,940 resulted in AT1-R up-regulation, indicating that AT1-R expression is directly regulated by the CB(1)-R. CB(2)-R inhibition had no impact on AT1-R expression in VSMC. Consistently, CB(1)-R inhibition decreased aortic AT1-R expression in vivo. CB(1)-R inhibition leads to decreased vascular AT1-R expression, NADPH oxidase activity and ROS production in vitro and in vivo. This antioxidative effect is associated with improved endothelial function in ApoE-/- mice, indicating beneficial direct vascular effects of CB(1)-R inhibition. PMID- 20361198 TI - TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease. AB - The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain-behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinico-anatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies. PMID- 20361199 TI - Treatment of 103 displaced tibial diaphyseal fractures with a radiolucent unilateral external fixator. AB - OBJECTIVE: The authors report their experience in the treatment of the diaphyseal tibial fractures, using the unilateral radiolucent External Fixator (EF) XCaliber. DESIGN: A total of 100 patients (average age 35 years, range 16-76) with 103 displaced diaphyseal tibial fractures were treated with the XCaliber. There were 59 type A fractures, 35 type B, and 9 type C (according to the AO classification) and 35 were open fractures. MAIN OUTCOME MEASUREMENTS: During the last assessment, patients were evaluated for level of pain, ability to perform weight-bearing activities, and number of residual deformities. RESULTS: The average follow-up time was 24 months, 3 patients (4 fractures) were excluded for final assessment and 1 patient moved abroad. Of the remaining 98 fractures, 83 (84.7%) healed with a single operation in a mean 21 weeks (SD 3.97; 12-38 weeks), 10 fractures had a delayed union and 5 fractures proceeded to a non-union. There were 13 complications. Among them, a loss of reduction was observed in 3 cases due to overload of the EF, in 3 cases, deep pin track infections were observed and 2 fractures healed with more than 1 cm of shortening. CONCLUSIONS: The results are encouraging, since both complex and open fractures were included in this study. The XCaliber was shown to be a valid unilateral external fixator, combining the advantage of radiolucency during application and radioscopic follow up with a stable and flexible fracture fixation. This represents the first report in the literature specifically examining treatment of tibial diaphyseal fractures with a radiolucent external fixator. PMID- 20361200 TI - Oxidative stress and ATPase6 mutation is associated with primary ovarian insufficiency. AB - PURPOSE: Primary ovarian insufficiency (POI) is a heterogeneous, multifactorial disorder. Though genetic anomalies, infections, autoimmune disorder and hormonal imbalance are few of the causes of POI, in the majority of patients (50-60%) no etiology has been identified. Mitochondrial bioenergetics and biogenesis play an important role in oocyte and embryo development, whereas mtDNA integrity and content are essential for the normal development of oocytes. ATPase6 helps to maintain the mt genome integrity, and mutations in ATPase6 are associated with overproduction of reactive oxygen species (ROS) in a variety of diseases; however, its role in POI has not been evaluated. Therefore, we planned to evaluate the potential role of ATPase6 gene mutations and associated oxidative stress in idiopathic cases of POI. METHODS: This pilot study included: 20 cases of POI with FSH level of >40 mIU/ml; 4 cases of occult ovarian insufficiency (occult OI) with irregular menses and mean FSH levels of 16.4 mIU/ml; and 20 age matched healthy female controls (FSH 2-5 mIU/ml). ROS levels in blood plasma were measured by luminol-dependent chemiluminescence assay and the ROS values were expressed as relative light unit per minute (RLU/min). mtDNA ATPase6 gene was amplified and sequenced from the blood lymphocyte DNA. RESULTS: Of all, 50% patients showed nucleotide changes in the ATPase6 gene, as compared to 10% in controls, and the majority of these mutations were non-synonymous. ATPase6 mt.8684 C>T and mt.9094 C>T were found to be significantly (P < 0.005) higher in cases as compared to controls. ROS levels were found to be significantly (P < 0.005) higher in POI and occult OI patients compared to controls and nucleotide changes were found to positively correlate with ROS levels. Moreover, ROS production was found to positively correlate (r = 0.7038, P < 0.001) with FSH levels of the patients (POI and OI) compared to controls. CONCLUSIONS: This pilot study clearly demonstrates for the first time ATPase6 gene nucleotide alterations and elevated ROS levels in idiopathic cases of POI. Therefore, it may be possible that OS associated with ATPase6 gene mutation may be causal in idiopathic cases of premature OI. However, larger studies with inclusion of more cases of both POI and occult OI are required to strongly establish the correlation between oxidative stress and mitochondrial nucleotide alterations in the pathogenesis of POI. Such cases with OS-induced POI may benefit immensely by early diagnosis and prompt antioxidant administration. PMID- 20361201 TI - p57KIP2 immunohistochemical expression: a useful diagnostic tool in discrimination between complete hydatidiform mole and its mimics. AB - PURPOSE: The purpose of this study was to evaluate the results of immunohistochemical expression of p57KIP2 in the complete hydatidiform mole (CHM) and other types of hydropic pregnancy. BACKGROUND: Classification of molar pregnancies is typically defined by histologic and genetic criteria. The histologic criteria are subjective and demonstrate considerable interobserver variability. Several studies have recently shown that immunohistochemical detection of p57KIP2 expression in molar pregnancies is a useful ancillary diagnostic tool. The p57KIP2 gene is strongly paternally imprinted and maternally expressed. The villous cytotrophoblastic cells of complete hydatidiform mole (CHM) lack the maternal genome, that's why they reveal negative immunostaining for p57KIP2. On the contrary, in villous cytotrophoblastic cells of partial hydatidiform mole (PHM) and hydropic abortion, immunohistochemical staining for this marker is positive. METHODS: We performed p57KIP2 immunohistochemical staining in 89 cases in four histological diagnostic categories as follows: "CHM" (n = 22), "PHM" (n = 32), "hydatidiform mole (HM)" (where the histological features were insufficient to differentiate between CHM and PHM) (n = 20), and "suggestive for PHM" (n = 15). RESULTS: p57KIP2 expression in villous cytotrophoblasts and stromal cells was absent or markedly reduced in 22 of 22 "CHMs", 7 of 32 "PHMs", 15 of 20 "HMs", and 1 of 15 "suggestive for PHMs" (P < 0.001). In all cases, maternal decidua and syncytiotrophoblast, respectively, showed diffuse and strong p57KIP2 expression, and negative p57KIP2 expression. CONCLUSIONS: This study confirms that negative p57KIP22 immunostaining may reliably identify CHM irrespective of gestational age and can be used in association with the histological findings to distinguish CHM from its mimics in challenging cases. PMID- 20361202 TI - Feasibility of office hysteroscopy through the "see and treat technique" in private practice: a prospective observational study. AB - PURPOSE: The purpose of the study was to examine the feasibility of office hysteroscopy through the no-touch "see and treat technique" in a routine basis in private practice. METHODS: In the private practice of two trained gynecologists, women with an indication for further investigation of the uterine cavity were treated with the technique. A total of 112 consecutive women were prospectively allocated to a "no-touch" and "see and treat" technique of hysteroscopy. Neither anaesthesia nor analgesia was used as soon as criteria were met. Hysteroscopy was performed using a rigid 3.4-mm hysteroscope and a medium of 0.9% saline. RESULTS: Treatment efficacy and patient compliance were evaluated through scores on a visual analogue scale (VAS) for pain, complications and success rates, along with the symphony between hysteroscopic findings and histology. The patients' pain score on the VAS was low and only in 2 out of 112 cases there was a marked discomfort. In four cases suggested treatment was not successful, because of the fear of the patient. In 60.71% of cases that hysteroscopy was indicated, the uterine cavity was normal. No complications or adverse effects were noted. Apart from one case, there was a full agreement between hysteroscopic findings and histology. CONCLUSION: Office hysteroscopy is a successful and well-tolerated procedure. Through adequate expertise it should be considered the method of choice in private basis, at the same time when exploration of the uterine cavity is needed. PMID- 20361203 TI - Adaptive force produced by stress-induced regulation of random variation intensity. AB - The Darwinian theory of life evolution is capable of explaining the majority of related phenomena. At the same time, the mechanisms of optimizing traits beneficial to a population as a whole but not directly to an individual remain largely unclear. There are also significant problems with explaining the phenomenon of punctuated equilibrium. From another perspective, multiple mechanisms for the regulation of the rate of genetic mutations according to the environmental stress have been discovered, but their precise functional role is not well understood yet. Here a novel mathematical paradigm called a Kinetic Force Principle (KFP), which can serve as a general basis for biologically plausible optimization methods, is introduced and its rigorous derivation is provided. Based on this principle, it is shown that, if the rate of random changes in a biological system is proportional, even only roughly, to the amount of environmental stress, a virtual force is created, acting in the direction of stress relief. It is demonstrated that KFP can provide important insights into solving the above problems. Evidence is presented in support of a hypothesis that the nature employs KFP for accelerating adaptation in biological systems. A detailed comparison between KFP and the principle of variation and natural selection is presented and their complementarity is revealed. It is concluded that KFP is not a competing alternative, but a powerful addition to the principle of variation and natural selection. It is also shown KFP can be used in multiple ways for adaptation of individual biological organisms. PMID- 20361204 TI - Maximizing contrast resolution in the outer retina of mammals. AB - The outer retina removes the first-order correlation, the background light level, and thus more efficiently transmits contrast. This removal is accomplished by negative feedback from horizontal cell to photoreceptors. However, the optimal feedback gain to maximize the contrast sensitivity and spatial resolution is not known. The objective of this study was to determine, from the known structure of the outer retina, the synaptic gains that optimize the response to spatial and temporal contrast within natural images. We modeled the outer retina as a continuous 2D extension of the discrete 1D model of Yagi et al. (Proc Int Joint Conf Neural Netw 1: 787-789, 1989). We determined the spatio-temporal impulse response of the model using small-signal analysis, assuming that the stimulus did not perturb the resting state of the feedback system. In order to maximize the efficiency of the feedback system, we derived the relationships between time constants, space constants, and synaptic gains that give the fastest temporal adaptation and the highest spatial resolution of the photoreceptor input to bipolar cells. We found that feedback which directly modulated photoreceptor calcium channel activation, as opposed to changing photoreceptor voltage, provides faster adaptation to light onset and higher spatial resolution. The optimal solution suggests that the feedback gain from horizontal cells to photoreceptors should be approximately 0.5. The model can be extended to retinas that have two or more horizontal cell networks with different space constants. The theoretical predictions closely match experimental observations of outer retinal function. PMID- 20361205 TI - Clinical course and outcome after esophagectomy with three-field lymphadenectomy in esophageal cancer. AB - BACKGROUND: Esophagectomy with three-field lymphadenectomy has been performed for esophageal cancer. Detailed analysis of cause of death and mode of recurrence is required to determine the need for further adjuvant therapy and follow-up. MATERIALS AND METHODS: A total of 208 patients who underwent esophagectomy through right thoracotomy with three-field lymphadenectomy were enrolled into the present study. Mode of first recurrence was divided into four groups: lymph node, hematogenous, mixed, and local recurrence. RESULTS: Excluding 16 hospital deaths, the number of deaths and 5-year survival rates were 104 patients and 7.8% for cancer recurrence, 12 patients and 53.8% for second primary cancers in other organs, and 34 patients and 31.0% for causes of death unrelated to carcinoma. In the 104 patients with relapse, 5-year survival rate of patients was 14.3% with lymph node recurrence (n = 29), 9.1% with hematogenous recurrence (n = 32), 3.1% with mixed recurrence (n = 35), and 12.5% with local recurrence (n = 8). CONCLUSION: To improve outcomes for esophagectomy with three-field lymphadenectomy, early detection of recurrent disease and regular examination of the entire body for secondary cancer is necessary. PMID- 20361206 TI - Cystic dysplasia of the epididymis: a disorder of mesonephric differentiation associated with renal maldevelopment. AB - The occurrence of congenital epididymal malformations with a cystic component has not been fully characterized. Most epididymal cysts occur later in life and are likely acquired. In addition, congenital malformations of the male excretory system are extremely uncommon in fetuses and neonates, and epididymal dysplastic changes have not been reported in these cases. In this study, we report 20 cases (including 19 fetal/neonatal autopsies and one surgical specimen from an older child) showing the same spectrum of histological findings in the epididymis, characterized by cystic ductal dilation with dysplastic ducts of variable diameters and irregular shapes, with ill-defined walls. Efferent ductules also showed dysplastic features. In addition, 18 cases had either renal and/or urinary tract anomalies, including renal dysplasia (eight), pelvicaliceal dilation (eight), renal agenesis (four) and hypoplasia (one), ureteral agenesis (two) and hypoplasia (one), urethra and bladder agenesis (two), prostate agenesis (two), and autosomal recessive polycystic renal disease (two). Our observations led to the recognition of a peculiar, not previously described congenital lesion of the epididymis, and we propose the term cystic dysplasia of the epididymis for this anomaly. Similar to what is observed in other male genital system anomalies (including malformations of the rete testis, vas deferens, and seminal vesicles), most lesions occurred in association with renal and/or urinary tract malformations, suggesting a spectrum of congenital malformations. The shared embryological origin of these structures may explain their simultaneous occurrence, possibly related to disrupted mesonephric duct development. PMID- 20361207 TI - Mergence of partial and complete atrophy in prostate needle biopsies: a morphologic and immunohistochemical study. AB - Partial atrophy is the most common benign lesion that causes difficulty in the differential diagnosis with adenocarcinoma of the prostate. Very few studies described, illustrated, and discussed the concomitance of partial atrophy with complete atrophy in prostatic needle biopsies. The study group comprised 75 needle prostatic biopsies corresponding to 67 patients. Focal prostatic atrophy was present in all biopsies. Complete atrophy was subtyped into simple atrophy, sclerotic atrophy, and hyperplastic atrophy (or postatrophic hyperplasia). We analyzed the presence of inflammation in the atrophic foci and immunohistochemistry was performed for p63, 34betaE12, and PSA. Partial atrophy and complete atrophy were present concomitantly in 47/75 (63%) biopsies. In 20/75 (27%) biopsies, there were areas with mergence of partial atrophy and complete atrophy. We illustrate morphologic transitions between these lesions in the same gland. Using immunohistochemistry, the aberrant phenotypic expression in the secretory compartment in all subtypes of complete atrophy highlighted the morphologic transitions between partial and complete atrophies in the same gland. An intriguing finding was the absence of chronic inflammation in partial atrophy foci as well as in areas of mergence between these lesions. Inflammation was present only in isolated complete focal atrophy foci. Partial atrophy seems to be part of a morphologic spectrum of focal prostatic atrophy and probably precedes complete atrophy. The question of whether the inflammation produces tissue damage and prostatic atrophy or whether some other insults like ischemia induces the tissue damage and atrophy directly, with inflammation occurring secondarily, is still unsettled. PMID- 20361208 TI - Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages. AB - Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD. PMID- 20361209 TI - Fine mapping of the 9q31 Hirschsprung's disease locus. AB - Hirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 x 10(-6) [OR = 3.32 (1.99, 5.59)] after replication. The HSCR association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. PMID- 20361211 TI - A computerized assessment to compare the impact of standard, stereoscopic, and high-definition laparoscopic monitor displays on surgical technique. AB - BACKGROUND: Surgeons performing laparoscopic surgery have strong biases regarding the quality and nature of the laparoscopic video monitor display. In a comparative study, we used a unique computerized sensing and analysis system to evaluate the various types of monitors employed in laparoscopic surgery. METHODS: We compared the impact of different types of monitor displays on an individual's performance of a laparoscopic training task which required the subject to move the instrument to a set of targets. Participants (varying from no laparoscopic experience to board-certified surgeons) were asked to perform the assigned task while using all three display systems, which were randomly assigned: a conventional laparoscopic monitor system (2D), a high-definition monitor system (HD), and a stereoscopic display (3D). The effects of monitor system on various performance parameters (total time consumed to finish the task, average speed, and movement economy) were analyzed by computer. Each of the subjects filled out a subjective questionnaire at the end of their training session. RESULTS: A total of 27 participants completed our study. Performance with the HD monitor was significantly slower than with either the 3D or 2D monitor (p < 0.0001). Movement economy with the HD monitor was significantly reduced compared with the 3D (p < 0.0004) or 2D (p < 0.0001) monitor. In terms of average time required to complete the task, performance with the 3D monitor was significantly faster than with the HD (p < 0.0001) or 2D (p < 0.0086) monitor. However, the HD system was the overwhelming favorite according to subjective evaluation. CONCLUSION: Computerized sensing and analysis is capable of quantitatively assessing the seemingly minor effect of monitor display on surgical training performance. The study demonstrates that, while users expressed a decided preference for HD systems, actual quantitative analysis indicates that HD monitors offer no statistically significant advantage and may even worsen performance compared with standard 2D or 3D laparoscopic monitors. PMID- 20361212 TI - Advantages of endoscopic submucosal dissection with needle-knife over endoscopic mucosal resection for small rectal carcinoid tumors: a retrospective study. AB - BACKGROUND: Endoscopic submucosal dissection (ESD) is a new, widely accepted method for the treatment of early gastric cancer and was developed to increase the en bloc resection rate. This study aimed to evaluate the efficacy and safety of ESD compared with conventional endoscopic mucosal resection (EMR) for small rectal carcinoid tumors. METHODS: A retrospective study was carried out that included 43 patients with small rectal carcinoid tumors (< 10 mm). The cohort comprised two groups: Group A (N = 23) underwent conventional EMR from January 2004 to August 2005, while group B (N = 20) underwent ESD with needle-knife from September 2005 to December 2006. The rate of curative en bloc resection, the procedure time, and the incidence of complications were evaluated. RESULTS: The en bloc resection rate and the rate of completeness of resection of group B were higher than those of group A (100 vs. 87%, 100 vs. 52.5%, respectively). The average operation time required for resection was significantly longer in group B (28.4 +/- 17.2 min) compared with group A (12.3 +/- 15.4 min) (p < 0.05). None of the patients had immediate or delayed bleeding during the procedure. Perforation occurred in one case of group B and the patient recovered after several days of conservative treatment. Three patients had local recurrence after EMR, while no patient experienced recurrence after ESD. CONCLUSION: ESD, compared with conventional EMR, increased en bloc and histologically complete resection rates and may reduce local recurrence rate for small rectal carcinoid tumors. Increased operation time and complication risks with ESD remain problematic. Further technique and investigation are required to confirm the safety and to assess the long-term prognosis of ESD. PMID- 20361213 TI - Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60 years of age. AB - BACKGROUND: The effectiveness of an esophagomyotomy for dysphagia in elderly patients with achalasia has been questioned. This study was designed to provide an answer. METHODS: A total of 162 consecutive patients with achalasia who had a laparoscopic myotomy and Dor fundoplication and who were available for follow-up interview were divided by age: < 60 years (range, 14-59; 118 patients), and >= 60 years (range, 60-93; 44 patients). Primary outcome measures were severity of dysphagia, regurgitation, heartburn, and chest pain before and after the operation as assessed on a four-point Likert scale, and the need for postoperative dilatation or revisional surgery. RESULTS: Follow-up averaged 64 months. Older patients had less dysphagia (mean score 3.6 vs. 3.9; P < 0.01) and less chest pain (1.0 vs. 1.8; P < 0.01). Regurgitation (3.0 vs. 3.2; P = not significant (NS)) and heartburn (1.6 vs. 2.0, P = NS) were similar. Older patients were no different in degree of esophageal dilation, manometric findings, number of previous pneumatic dilatations, or previous botulinum toxin therapy. None of the older patients had previously had an esophagomyotomy, whereas 14% of younger patients had (P < 0.01). After laparoscopic myotomy, older patients had better relief of dysphagia (mean score 1.0 vs 1.6; P < 0.01), less heartburn (0.8 vs. 1.1; P = 0.03), and less chest pain (0.2 vs. 0.8, P < 0.01). Complication rates were similar. Older patients did not require more postoperative dilatations (22 patients vs. 10 patients; P = 0.7) or revisional surgery for recurrent or persistent symptoms (3 vs. 1 patients; P = 0.6). Satisfaction scores did not differ, and more than 90% of patients in both groups said in retrospect they would have undergone the procedure if they had known beforehand how it would turn out. CONCLUSIONS: This retrospective review with long follow-up supports laparoscopic esophagomyotomy as first-line therapy in older patients with achalasia. They appeared to benefit even more than younger patients. PMID- 20361214 TI - Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn's disease: relevance to local angiotensin II system. AB - BACKGROUND: Intestinal stricture lesions in Crohn's disease are characterized as submucosal fibromuscular accumulation. There has been a controversy about whether the fibrogenic cells in stricture lesions in Crohn's disease originate from a smooth muscle cell or a fibroblast lineage. In the present study, we aimed to elucidate: (1) the origin of the fibrogenic cells in stricture lesions; and (2) the roles of the local angiotensin II system, including mast cell chymase, in stricture formation. METHODS: Methanol-Carnoy's-fixed colonic tissues, obtained from the stricture sites of 18 patients with Crohn's disease, were analyzed by immunostaining for vimentin, smooth muscle actin (1A4 and CGA7), angiotensin II type-1 receptor, angiotensin II-converting enzyme, and mast cell tryptase and chymase. As controls, unaffected (normal) portions of 11 colonic tumor specimens were also investigated. RESULTS: Submucosal fibromuscular accumulation was seen in every stricture lesion. The majority of mesenchymal cells accumulated in the stricture lesions were moderately differentiated intestinal smooth muscle cells [vimentin(+), 1A4(+), and CGA7(+)]. Moreover, occasional intestinal smooth muscle cells in the muscular layers, adjacent to the site of the submucosal fibromuscular response, showed distinct positivity for vimentin, indicating phenotypic modulation toward an immature, or dedifferentiated state. These smooth muscle cells accumulated in the stricture lesions were positive for angiotensin II type-1 receptor. Abundant chymase-positive mast cells were distributed in these lesions. CONCLUSIONS: These results suggest that the proliferation and migration of moderately differentiated intestinal smooth muscle cells from the muscular layers are the major pathological mechanisms in stricture formation in Crohn's disease, and the angiotensin II system is involved in this process. PMID- 20361215 TI - Stereotactic radiofrequency amygdalohippocampectomy in the treatment of mesial temporal lobe epilepsy. AB - PURPOSE: Minimally invasive percutaneous single trajectory stereotactic radiofrequency amygdalohippocampectomy was used to treat mesial temporal lobe epilepsy (MTLE). The aim of the study was to evaluate complications and effectiveness of this procedure. MATERIALS AND METHODS: A group of 51 patients with MTLE was treated using stereotactic thermo-lesion of amygdalohippocampal complex under local anaesthesia. The target was reached through the occipital approach with a single trajectory using MRI stereotactic localisation. Thermocoagulation of the amygdalohippocampal complex was planned according to the individual anatomy of each patient. Amygdalohippocampectomy was performed using a string electrode with a 10-mm active tip, and 16-38 lesions (median = 25) were performed in all patients along the 30- to 45-mm trajectory (median = 35) in the amygdalohippocampal complex. RESULTS: The procedure was well tolerated by all patients with no severe permanent morbidity; meningitis was recorded in two patients (4%), hematoma was detected in four patients, clinically insignificant in three of them, and one patient required temporary ventricular drainage (2%). Thirty-two patients were followed up over at least 2 years, and the clinical outcomes were evaluated by Engel's classification; 25 of them (78%) were Engel I, five (16%) were Engel II, and two (6%) were Engel IV. CONCLUSIONS: Stereotactic amygdalohippocampectomy is a minimally invasive procedure with low morbidity and good results that can be the method of choice in selected patients with MTLE. PMID- 20361216 TI - The long-term outcome of delinquent children: a 30-year follow-up study. AB - This study reports the results of a longitudinal study of unselected samples of German delinquent children, stratified by frequency of offences recorded before and after the age of criminal responsibility (14 years). A total of 256 young adults (mean age, 22 years), juvenile offenders and control non-offenders, were assessed using the following: a standardized interview regarding family, child development and life history; a multidimensional personality inventory (the Freiburg Personality Inventory, FPI); a version of the Wechsler Adult Intelligence Scale; a self-report questionnaire on the delinquency for which the subject was not apprehended during childhood; and a questionnaire concerning parental child-rearing style. The subsequent criminal records of subjects were followed over the next 20 years. It was possible to define three outcome groups (non-offenders, persisters and desisters), which differed in many respects. The outcome was significantly predicted by several variables. Psychosocial risk variables were the most effective predictors, followed by personality variables and childhood delinquency for which the subject had not been apprehended. The distinction between early-onset and late-onset delinquency as a predictor of adult criminality proved valid only if non-apprehended childhood offending was taken into account. The implications of the study for preventive intervention are discussed. PMID- 20361217 TI - Amino acid metabolism in the portal-drained viscera of young pigs: effects of dietary supplementation with chitosan and pea hull. AB - Recent studies indicate extensive catabolism of amino acids (AA) by the portal drained viscera (PDV) of pigs and humans. Because of ethical concerns over invasive surgical procedures on infants or adults, in vivo investigations are often performed with the pig which is both an agriculturally important livestock species and a widely used animal model for nutritional and physiological studies in humans. Here, we described a new technique for implanting chronic catheters into the portal vein, ileal mesenteric vein, and carotid artery to study AA metabolism in the PDV of young pigs. This method allowed for the reduction of surgery time by 1 h and measurements of the entry of dietary AA into the portal circulation. Using such an approach, we found that dietary supplementation with 100 mg/kg chitosan (a prebiotic and a polysaccharide not digested by animal cells) reduced oxygen consumption, as well as the net absorption of dietary AA into the portal vein, thereby enhancing their bioavailability for extraintestinal tissues. In contrast, opposite results were obtained with dietary supplementation of 12% pea-hull (containing 95% of fermentable nonstarch polysaccharide). Thus, this improved technique is useful to quantify in vivo absorption and metabolism of dietary AA in young pigs. PMID- 20361219 TI - 2-alkyl-2-carboxyazetidines as gamma-turn inducers: incorporation into neurotrophin fragments. AB - Conveniently substituted 2-alkyl-2-carboxyazetidine amino acids have been incorporated into NGF and NT3 tetrapeptide sequences to investigate their utility as reverse turn inducers (gamma- vs. beta-turns). Despite the presence of an Asp residue at i position, highly preferred in beta-turns, molecular modeling and NMR studies indicated that the azetidine-containing peptides mainly stabilized gamma turn conformations. PMID- 20361218 TI - Gene expression and integrated stress response in HepG2/C3A cells cultured in amino acid deficient medium. AB - The integrated stress response (ISR), a defense mechanism cells employ when under stress (e.g., amino acid deprivation), causes suppression of global protein synthesis along with the paradoxical increased expression of a host of proteins that are useful in combating various stresses. Genes that were similarly differentially expressed under conditions of either leucine- or cysteine depletion were identified. Many of the genes known to contain an amino acid response element and to be induced in response to eIF2alpha phosphorylation and ATF4 heterodimer binding (ATF3, C/EBPbeta, SLC7A1, SLC7A11, and TRIB3), as well as others shown to be induced downstream of eIF2alpha phosphorylation (C/EBPgamma, CARS, SARS, CLCN3, CBX4, and PPP1R15A) were among the upregulated genes. Evidence for the induction of the ISR in these cells also included the increased phosphorylation of eIF2alpha and increased protein abundance of ATF4, ATF3, and ASNS in cysteine- and leucine-depleted cells. Based on genes highly differentially expressed in both leucine- and cysteine-deficient cells, a list of 67 downregulated and 53 upregulated genes is suggested as likely targets of essential amino acid deprivation in mammalian cells. PMID- 20361220 TI - The first step of the dioxygenation reaction carried out by tryptophan dioxygenase and indoleamine 2,3-dioxygenase as revealed by quantum mechanical/molecular mechanical studies. AB - Tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are two heme containing enzymes which catalyze the conversion of L: -tryptophan to N formylkynurenine (NFK). In mammals, TDO is mostly expressed in liver and is involved in controlling homeostatic serum tryptophan concentrations, whereas IDO is ubiquitous and is involved in modulating immune responses. Previous studies suggested that the first step of the dioxygenase reaction involves the deprotonation of the indoleamine group of the substrate by an evolutionarily conserved distal histidine residue in TDO and the heme-bound dioxygen in IDO. Here, we used classical molecular dynamics and hybrid quantum mechanical/molecular mechanical methods to evaluate the base-catalyzed mechanism. Our data suggest that the deprotonation of the indoleamine group of the substrate by either histidine in TDO or heme-bound dioxygen in IDO is not energetically favorable. Instead, the dioxygenase reaction can be initiated by a direct attack of heme-bound dioxygen on the C(2)=C(3) bond of the indole ring, leading to a protein-stabilized 2,3-alkylperoxide transition state and a ferryl epoxide intermediate, which subsequently recombine to generate NFK. The novel sequential two-step oxygen addition mechanism is fully supported by our recent resonance Raman data that allowed identification of the ferryl intermediate (Lewis Ballester et al. in Proc Natl Acad Sci USA 106:17371-17376, 2009). The results reveal the subtle differences between the TDO and IDO reactions and highlight the importance of protein matrix in modulating stereoelectronic factors for oxygen activation and the stabilization of both transition and intermediate states. PMID- 20361221 TI - The metal-binding properties of the blue crab copper specific CuMT-2: a crustacean metallothionein with two cysteine triplets. AB - Most crustacean metallothioneins (MTs) contain 18 Cys residues and bind six divalent metal ions. The copper-specific CuMT-2 (MTC) of the blue crab Callinectes sapidus with 21 Cys residues, of which six are organized in two uncommon Cys-Cys-Cys sequences, represents an exception. However, its metal binding properties are unknown. By spectroscopic and spectrometric techniques we show that all 21 Cys residues of recombinant MTC participate in the binding of Cu(I), Zn(II), and Cd(II) ions, indicating that both Cys triplets act as ligands. The fully metallated M(8) (II)-MTC (M is Zn, Cd) form possesses high- and low affinity metal binding sites, as evidenced by the formation of Zn(6)-MTC and Cd(7)-MTC species from M(8) (II)-MTC after treatment with Chelex 100. The NMR characterization of Cd(7)-MTC suggests the presence of a two-domain structure, each domain containing one Cys triplet and encompassing either the three-metal or the four-metal thiolate cluster. Whereas the metal-Cys connectivities in the three-metal cluster located in the N-terminal domain (residues 1-31) reveal a Cd(3)Cys(9) cyclohexane-like structure, the presence of dynamic processes in the C-terminal domain (residues 32-64) precluded the determination of the organization of the four-metal cluster. Absorption and circular dichroism features accompanying the stepwise binding of Cu(I) to MTC suggest that all 21 Cys are involved in the binding of eight to nine Cu(I) ions (Cu(8-9)-MTC). The subsequent generation of Cu(12)-MTC involves structural changes consistent with a decrease in the Cu(I) coordination number. Overall, the metal-binding properties of MTC reported here contribute to a better understanding of the role of Cys triplets in MTs. PMID- 20361222 TI - Are children with ADHD predominantly inattentive and combined subtypes different in terms of aspects of everyday attention? AB - The validity of the DSM-IV subtypes is a recurring diagnostic debate in attention deficit/hyperactivity disorder (ADHD). Laboratory measures, such as the test of everyday attention for children (TEA-Ch) can help us address this question. TEA Ch is a test battery covering different aspects of everyday attention relating to selective and sustained attention and attentional control. The aim of the current study was to investigate whether this instrument can differentiate between combined (ADHD-C) and inattentive subtype (ADHD-I) of ADHD. Subjects were recruited from a multidisciplinary ADHD outpatient unit and tested free of medication. Sixty-four children with a diagnosis of ADHD were included (38 with ADHD-C; 26 with ADHD-I). The control group was 76 children recruited from primary and secondary schools. Children with ADHD performed worse than controls on 6 out of 9 TEA-Ch subtests. However a regression analysis revealed that TEA-Ch subtests made only a marginal contribution to the correct classification of ADHD, once the effects of IQ and age are controlled. Confirmatory factor analysis in our ADHD group demonstrated that the three factor structure achieved a poor fit. More detailed analysis suggested that inferior performance on the tasks designed to test vigilance was not the result of deficient-sustained attention. ADHD-C and ADHD-I showed very few differences across tasks. In conclusion, our results provided not much support for the value of the ADHD-C and ADHD-I distinction in predicting difficulties in everyday attention. PMID- 20361224 TI - Hormonal therapy in a patient with ovarian agenesis and possible SLE: a choice to be made. AB - Systemic lupus erythromatosus (SLE) is an autoimmune disease, which affects mainly women in the reproductive age and is influenced by hormonal changes. Therefore, hormone supplementation for patients with SLE either as contraceptives or as postmenopausal supplementation remains a controversial issue. Herein, we report a case of a 22-year-old woman with a history of ovarian agenesis, treated for several years with hormone therapy in order to reduce the risk of osteoporosis and other estrogen-deficient disorders. At the current evaluation, she met 3 of 11 diagnostic criteria for SLE along with a strong familial autoimmune predisposition. Precipitation of SLE in patients treated with hormonal therapy has been previously described. This prompted us to seek alternative drug therapies that prevent both the onset of overt SLE as well as the progression of estrogen-deficient phenomena. This unique case illustrates the dilemma of using hormone therapy in patients at risk to develop SLE and the current therapeutic alternatives. PMID- 20361225 TI - Teaching knee joint aspiration to medical students-an effective training with long-term benefits. AB - The objective of this study was to assess the effectiveness of undergraduate training in knee aspiration and to determine the impact this had on subsequent postgraduate clinical practice. This paper is a cohort study of undergraduate training with a cross-sectional questionnaire study of postgraduate practice. The study was held at the University of Cambridge and NHS hospitals in the Eastern Region Postgraduate Deanery (England). The main outcome measures are the undergraduate competence in practical skills in a simulated setting and the differences in postgraduate practice with or without prior undergraduate training in knee aspiration. Implementing an undergraduate training programme in knee aspiration resulted in student competence in this skill. Undergraduate teaching of knee aspiration also improved postgraduate clinical practice, significantly increasing trainee doctor confidence and also increasing the frequency with which knee aspiration was undertaken. Postgraduate reinforcement of learning was identified as an additional requirement. Undergraduate teaching of knee aspiration not only results in competent performance in end of course assessments but also improves postgraduate confidence that potentially translates into improved clinical practice. PMID- 20361226 TI - Social capital as a determinant of self-rated health and psychological well being. AB - OBJECTIVE: To examine whether specific dimensions of social capital are related to self-rated health and psychological well-being. METHODS: Cross-sectional data from a health survey representing the adult Finnish population (N = 8,028) were used. Logistic regression analysis was used to reveal and quantify the possible associations between three dimensions of social capital (social support; social participation and networks; trust and reciprocity) and two general health indicators (self-rated health and psychological well-being). The roles of age, gender, education, living arrangements, income, type of region, functional capacity, and long-standing illness were also assessed. RESULTS: Good self-rated health was associated with high levels of social participation and networks and trust and reciprocity, but social support did not remain statistically significant after adjustment for socio-demographic factors, long-standing illness, and functional capacity. The association between social support and psychological well-being was explained by the other two dimensions of social capital. The strong positive association between trust and psychological well being persisted after controlling for all the other factors in our model. CONCLUSIONS: Our findings suggest that trust and reciprocity and social participation and networks contribute to good self-rated health and psychological well-being. PMID- 20361227 TI - Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid. AB - We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H(2)O(2) or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion dependent apoptosis. PMID- 20361228 TI - Inadequate cytoplasmatic calcium signals in alveolar macrophages after cardiac surgery. AB - OBJECTIVE AND DESIGN: Patients undergoing cardiac surgery have an elevated risk for pulmonary complications. A dysfunction of alveolar macrophages (AM) might promote postoperative infections. Therefore intracellular calcium [Ca(2+)](i) as an important second messenger in cellular signaling was assessed in AM. MATERIALS AND METHODS: Twelve patients undergoing elective coronary artery bypass graft surgery (CABG) were enrolled in this clinical trial. After anesthesia induction and 2 h after cardiopulomary bypass (CPB) declamping, the bronchoalveolar lavage (BAL) fluid was collected preoperatively from the right middle lobe and postoperatively from the left lingula of the lung. Cell subpopulations and [Ca(2+)](i) signals were assessed via flow cytometry. To express the changes of [Ca(2+)](i) signals the Fluo4/FuraRed-Ratio was used. RESULTS: After surgery the [Ca(2+)](i) baseline in unstimulated AMs were significantly reduced (p < 0.001). A significant signal reduction after fMLP (p = 0.021) and C5a (p = 0.028) stimulation was found in FSC high AMs after surgery, even though all populations showed a trend of less responsiveness. CONCLUSION: We suggest that the reduced [Ca(2+)](i) signaling in postoperative AMs is caused by a reduced coupling to membrane channels. These preliminary data suggest an inadequate [Ca(2+)](i) signal of AM after surgery, which may contribute to a local immune dysfunction in the lung. PMID- 20361229 TI - Enhanced 1,3-propanediol production by supply of organic acids and repeated fed batch culture. AB - In fed-batch culture of Klebsiella pneumoniae, 1,3-propanediol production was growth associated, while the by-products, including lactic acid and ethanol, increased sharply as the cells grew slowly. When the fed-batch culture was supplied with a mixture of organic acids including citrate, fumarate and succinate, cell growth and 1,3-propanediol production increased significantly, whereas the by-products, especially lactic acid and ethanol, decreased sharply. High concentrations of PDO and acetate inhibited cell growth and PDO production. To improve the PDO production, repeated fed-batch culture with addition of the organic acid mixture was performed in a 5-l reactor. The fed-batch culture was repeated five times, and the 1,3-propanediol yield and concentration reached above 0.61 mol mol(-1) and 66 g l(-1), respectively, in 20 h for each cycle. Furthermore, the PDO productivity reached above 3.30 g l(-1) h(-1) in each cycle, which was much higher than that of the original fed-batch culture. PMID- 20361230 TI - Ecological integrity of streams related to human cancer mortality rates. AB - Assessments of ecological integrity have become commonplace for biological conservation, but their role for public health analysis remains largely unexplored. We tested the prediction that the ecological integrity of streams would provide an indicator of human cancer mortality rates in West Virginia, USA. We characterized ecological integrity using an index of benthic macroinvertebrate community structure (West Virginia Stream Condition Index, SCI) and quantified human cancer mortality rates using county-level data from the Centers for Disease Control and Prevention. Regression and spatial analyses revealed significant associations between ecological integrity and public health. SCI was negatively related to age-adjusted total cancer mortality per 100,000 people. Respiratory, digestive, urinary, and breast cancer rates increased with ecological disintegrity, but genital and oral cancer rates did not. Smoking, poverty, and urbanization were significantly related to total cancer mortality, but did not explain the observed relationships between ecological integrity and cancer. Coal mining was significantly associated with ecological disintegrity and higher cancer mortality. Spatial analyses also revealed cancer clusters that corresponded to areas of high coal mining intensity. Our results demonstrated significant relationships between ecological integrity and human cancer mortality in West Virginia, and suggested important effects of coal mining on ecological communities and public health. Assessments of ecological integrity therefore may contribute not only to monitoring goals for aquatic life, but also may provide valuable insights for human health and safety. PMID- 20361231 TI - A new infusion sustainer that stabilizes perfusion during sutureless 25-gauge vitrectomy. AB - To stabilize perfusion during sutureless 25-gauge (25G) vitrectomy, we designed an infusion sustainer and examined its usefulness. A reusable infusion sustainer was constructed by soldering a piece of metal wire to a metal paper clip and curling the two ends of the wire. For use, the sustainer was clipped onto the lip retractor, and the infusion line and chandelier fiber were passed through the wire loops. 25G vitrectomy was conducted in three porcine eyes, with insertion of a tonometer to monitor intraocular pressure (IOP). The relation between infusion port direction and IOP was examined. In a clinical study, 30 eyes that underwent 25G vitrectomy using the infusion sustainer and 30 eyes without using the infusion sustainer were compared for IOP maintenance and complications. In the porcine eye, after angled incision, the infusion tip was pointing toward the basal vitreous on the anterior side of the eyeball. Under these conditions, vitreous resection was accompanied by IOP lowering. When the infusion tip was moved so as to be directed toward the central vitreous, IOP was maintained. In the clinical study, among the eyes undergoing vitrectomy without the infusion sustainer, IOP decreased during operation in 30 eyes, and infusion fluid or air flowed into the anterior chamber in four eyes. In the 30 eyes in which the sustainer was used, no IOP lowering and no infusion fluid or air flow into the anterior chamber were detected, due to stabilization of the infusion port. Use of the infusion sustainer orients the infusion port toward the central vitreous, stabilizes IOP and prevents flow of infusion fluid or air into the anterior chamber. This infusion sustainer is useful to perform sutureless 25G vitrectomy safely. PMID- 20361232 TI - A novel esterase Sso2518 from Sulfolobus solfataricus with a much lower temperature optimum than the growth temperature. AB - An esterase, Sso2518, from Sulfolobus solfataricus P2 was over-expressed in E. coli. and characterized after purification. The maximum activity was at pH 7.5 and 50 degrees C. The half life of Sso2518 was about 30 min at 85 degrees C and the enzyme was activated by Cu(2+). The catalytic triad of Sso2518 was comprised of residues Ser151, Asp176, and His328. Sso2518 showed the highest activity with p-nitrophenyl caproate (C6) and could also hydrolyze olive oil. Under native conditions, Sso2518 consists of 125 kDa homotrimers. PMID- 20361233 TI - Interaction between Oenococcus oeni and Lactobacillus hilgardii isolated from wine. Modification of available nitrogen and biogenic amine production. AB - During the mixed culture of Lactobacillus hilgardii 5w, a common spoilage wine bacteria and Oenococcus oeni X(2)L, an amensalistic growth response of the malolactic bacteria was produced due to a competition for nitrogenous nutrients, mainly peptides. Arginine was fully consumed and peptide concentration diminished 60% with respect to both pure cultures at the end of exponential growth. Histamine release increased 34% with respect to L. hilgardii single culture. Under the poor nutritional conditions present during winemaking, L. hilgardii could increase histamine production and adversely affect malolactic fermentation conducted by O. oeni and hence the quality of the final product. PMID- 20361234 TI - Validation of reference genes of grass carp Ctenopharyngodon idellus for the normalization of quantitative real-time PCR. AB - Expression of four reference genes of grass carp, including beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA (18S) and elongation factor-1 alpha (EF1alpha), was studied in tissues of normal individuals and bacteria-infected individuals. EF1alpha had the most stable expressions followed by 18S rRNA then GAPDH; ACTB had the least stability. After being infected with bacteria, the grass carp showed minimal changes in expression levels of EF1alpha in the liver and head kidney, while ACTB had the most stable expressions in spleen but the least stable in liver. EF1alpha is thus the optimal reference gene in quantitative real-time PCR analysis to quantitate the expression levels of target genes in tissues of grass carp. PMID- 20361235 TI - Molecular cloning and sequence analysis of a mannitol dehydrogenase gene and isolation of mdh promoter from Candida magnoliae. AB - The mdh gene encodes mannitol dehydrogenase (MDH), which catalyzes the conversion of fructose into mannitol. The putative mdh gene of Candida magnoliae was isolated by PCR using the primers deduced from the N-terminal amino acid sequences of an intact MDH and its tryptic peptides, cloned in E. coli, and sequenced. The mdh gene consisted of 852 bp encoding for 283 amino acids. Analysis of the amino acid sequence revealed that MDH consisted of typical NADPH dependent short chain dehydrogenases/reductases (SDRs). To develop a strong promoter to induce expression of the foreign genes in C. magnolia, the putative promoter was isolated. The reporter protein, GFP, was well-expressed under the control of the putative mdh promoter of 153 bp in C. magnoliae. PMID- 20361236 TI - Colonization of sorghum and wheat by seed inoculation with Gluconacetobacter diazotrophicus. AB - Colonization of sorghum and wheat after seed inoculation with Gluconacetobacter diazotrophicus strains PAL 5 and UAP 5541/pRGS561 (containing the marker gene gusA) was studied by colony counting and microscopic observation of plant tissues. Inoculum levels as low as 10(2) CFU per seed were enough for root colonization and further spreading in aerial tissues. Rhizoplane colonization was around 7 log CFU g(-1) (fresh weight). G. diazotrophicus was found inside sorghum and wheat roots with populations higher than 5 log CFU g(-1) (fresh weight). Stem colonization remained stable for 30 days post inoculation with endophyte concentrations from 4 to 5 log CFU g(-1) (fresh weight) (in both plants). Population in leaves decreased continuously being undetectable after 17 days post inoculation. PMID- 20361237 TI - Site of metabolism prediction on cytochrome P450 2C9: a knowledge-based docking approach. AB - A novel structure-based approach for site of metabolism prediction has been developed. This knowledge-based method consists of three steps: (1) generation of possible metabolites, (2) docking the predicted metabolites to the CYP binding site and (3) selection of the most probable metabolites based on their complementarity to the binding site. As a proof of concept we evaluated our method by using MetabolExpert for metabolite generation and Glide for docking into the binding site of the CYP2C9 crystal structure. Our method could identify the correct metabolite among the three best-ranked compounds in 69% of the cases. The predictive power of our knowledge-based method was compared to that achieved by substrate docking and two alternative literature approaches. PMID- 20361238 TI - Combinatorial-computational-chemoinformatics (C3) approach to finding and analyzing low-energy tautomers. AB - Finding the most stable tautomer or a set of low-energy tautomers of molecules is critical in many aspects of molecular modelling or virtual screening experiments. Enumeration of low-energy tautomers of neutral molecules in the gas-phase or typical solvents can be performed by applying available organic chemistry knowledge. This kind of enumeration is implemented in a number of software packages and it is relatively reliable. However, in esoteric cases such as charged molecules in uncommon, non-aqueous solvents there is simply not enough available knowledge to make reliable predictions of low energy tautomers. Over the last few years we have been developing an approach to address the latter problem and we successfully applied it to discover the most stable anionic tautomers of nucleic acid bases that might be involved in the process of DNA damage by low-energy electrons and in charge transfer through DNA. The approach involves three steps: (1) combinatorial generation of a library of tautomers, (2) energy-based screening of the library using electronic structure methods, and (3) analysis of the information generated in step (2). In steps 1-3 we employ combinatorial, computational and chemoinformatics techniques, respectively. Therefore, this hybrid approach is named "Combinatorial*Computational*Chemoinformatics", or just abbreviated as C(3) (or C cube) approach. This article summarizes our developments and most interesting methodological aspects of the C(3) approach. It can serve as an example how to identify the most stable tautomers of molecular systems for which common chemical knowledge had not been sufficient to make definite predictions. PMID- 20361239 TI - Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism. AB - CYP2D6 is an important enzyme that is involved in first pass metabolism and is responsible for metabolizing ~25% of currently marketed drugs. A homology model of CYP2D6 was built using X-ray structures of ligand-bound CYP2C5 complexes as templates. This homology model was used in docking studies to rationalize and predict the site of metabolism of known CYP2D6 substrates. While the homology model was generally found to be in good agreement with the recently solved apo (ligand-free) X-ray structure of CYP2D6, significant differences between the structures were observed in the B' and F-G helical region. These structural differences are similar to those observed between ligand-free and ligand-bound structures of other CYPs and suggest that these conformational changes result from induced-fit adaptations upon ligand binding. By docking to the homology model using Glide, it was possible to identify the correct site of metabolism for a set of 16 CYP2D6 substrates 85% of the time when the 5 top scoring poses were examined. On the other hand, docking to the apo CYP2D6 X-ray structure led to a loss in accuracy in predicting the sites of metabolism for many of the CYP2D6 substrates considered in this study. These results demonstrate the importance of describing substrate-induced conformational changes that occur upon binding. The best results were obtained using Glide SP with van der Waals scaling set to 0.8 for both the receptor and ligand atoms. A discussion of putative binding modes that explain the distribution of metabolic sites for substrates, as well as a relationship between the number of metabolic sites and substrate size, are also presented. In addition, analysis of these binding modes enabled us to rationalize the typical hydroxylation and O-demethylation reactions catalyzed by CYP2D6 as well as the less common N-dealkylation. PMID- 20361240 TI - para-Nitrophenol 4-monooxygenase and hydroxyquinol 1,2-dioxygenase catalyze sequential transformation of 4-nitrocatechol in Pseudomonas sp. strain WBC-3. AB - Pseudomonas sp. strain WBC-3 utilizes para-nitrophenol (PNP) as a sole source of carbon, nitrogen and energy. PnpA (PNP 4-monooxygenase) and PnpB (para benzoquinone reductase) were shown to be involved in the initial steps of PNP catabolism via hydroquinone. We demonstrated here that PnpA also catalyzed monooxygenation of 4-nitrocatechol (4-NC) to hydroxyquinol, probably via hydroxyquinone. It was the first time that a single-component PNP monooxygenase has been shown to catalyze this conversion. PnpG encoded by a gene located in the PNP degradation cluster was purified as a His-tagged protein and identified as a hydroxyquinol dioxygenase catalyzing a ring-cleavage reaction of hydroxyquinol. Although all the genes necessary for 4-NC metabolism seemed to be present in the PNP degradation cluster in strain WBC-3, it was unable to grow on 4-NC as a sole source of carbon, nitrogen and energy. This was apparently due to the substrate's inability to trigger the expression of genes involved in degradation. Nevertheless, strain WBC-3 could completely degrade both PNP and 4-NC when PNP was used as the inducer, demonstrating its potential in bioremediation of the environment polluted by both 4-NC and PNP. PMID- 20361241 TI - Initial biocompatibility and enhanced osteoblast response of Si doping in a porous BCP bone graft substitute. AB - Granular shape biphasic calcium phosphate (BCP) bone grafts with and without doping of silicon cations were evaluated in regards to biocompatibility and MG-63 cellular response. To do this we studied Cellular cytotoxicity, cellular adhesion and spreading behavior and cellular differentiation with alizarin red S staining. Gene expression in MG-63 cells on the implanted bone substitutes was also examined at different time points using RT-PCR. In comparison, the Si-doped BCP granule showed more cellular viability than the BCP granule without doping in MTT assay. Moreover, cell proliferation was much higher when Si doping was employed. The cells grown on the silicon-doped BCP substitutes had more active filopodial growth with cytoplasmic webbing that proceeded to the flattening stage, which was indicative of well cellular adhesion. When these cells were exposed to Si-doped BCP granules for 14 days, well differentiated MG-63 cells were observed. Osteonectin and osteopontin genes were highly expressed in the late stage of differentiation (14 days), whereas collagen type I mRNA were found to be highly expressed during the early stage (day 3). These combined results of this study demonstrate that silicon-doped BCP enhanced osteoblast attachment/spreading, proliferation, differentiation and gene expression. PMID- 20361242 TI - The benefits of designing a stratification system for New York City pediatric intensive care units for use in regional surge capacity planning and management. AB - Accurate assessment of New York City (NYC) pediatric intensive care unit (PICU) resources and the ability to surge them during a disaster has been recognized as an important citywide emergency preparedness activity. However, while NYC hospitals with PICUs may be expected to surge in a disaster, few of them have detailed surge capacity plans. This will likely make it difficult for them to realize their full surge capacity both on individual and regional levels. If the pediatric resources that each NYC PICU hospital has can be identified prior to a disaster, this information can be used to both determine appropriate surge capacity goals for each PICU hospital and the additional resources needed to reach those goals. City agencies can then focus citywide planning efforts on making these resources available and more easily anticipate what a hospital will need during a disaster. Communication of this hospital information both prior to and during a surge situation will be aided by a stratification system familiar to both city planners and hospitals. The goal of this project was to design a NYC PICU surge stratification system that would aid physicians, hospitals and city agencies in regional surge capacity planning for critical pediatric patients. This goal was demonstrated through two objectives. The first identified major factors to consider when designing a stratification system. The second devised a preliminary system of PICU stratification based on clinical criteria and resources. PMID- 20361243 TI - Onset patterns prior to 36 months in autism spectrum disorders. AB - The present study investigated differences among children with three different patterns of autism symptom onset: regression, plateau, and no loss and no plateau. Cross-sectional data were collected from parents of children aged 3-17 years with an autism spectrum disorder (n = 2,720) who were recruited through a US-based online research database. Parental report of developmental characteristics was assessed through a parent questionnaire, and current autism symptoms were measured via the Social Responsiveness Scale and Social Communication Questionnaire. Multivariate analyses indicated that children with regression had a distinct developmental pattern marked by less delayed early development. However, following regression, these children evinced elevated autism symptom scores and an increased risk for poorer outcomes when compared with the other onset groups. PMID- 20361244 TI - Brief report: altered horizontal binding of single dots to coherent motion in autism. AB - Individuals with autism often show a fragmented way of perceiving their environment, suggesting a disorder of information integration, possibly due to disrupted communication between brain areas. We investigated thirteen individuals with high-functioning autism (HFA) and thirteen healthy controls using the metastable motion quartet, a stimulus consisting of two dots alternately presented at four locations of a hypothetical square, thereby inducing an apparent motion percept. This percept is vertical or horizontal, the latter requiring binding of motion signals across cerebral hemispheres. Decreasing the horizontal distance between dots could facilitate horizontal percepts. We found evidence for altered horizontal binding in HFA: Individuals with HFA needed stronger facilitation to experience horizontal motion. These data are interpreted in light of reduced cross-hemispheric communication. PMID- 20361246 TI - Sense of coherence and coping with stress among mothers and fathers of children with autism. AB - The purpose of the study was to compare the level of sense of coherence (SOC) in parents of children with autism and in parents of typically developing children, and to examine the association between SOC level and coping strategies. Two questionnaires were used: Sense of Coherence Scale (SOC-29) and Ways of Coping Questionnaire. Parents of children with autism had a lower level of the total SOC, meaningfulness, and manageability compared with controls, and used escape avoidance coping more often. No differences in SOC level were found between mothers and fathers. In parents of children with autism the SOC level was positively associated with seeking social support and self-controlling, and negatively with accepting responsibility and positive reappraisal. PMID- 20361245 TI - Changes in the autism behavioral phenotype during the transition to adulthood. AB - We examined whether exiting high school was associated with alterations in rates of change in autism symptoms and maladaptive behaviors. Participants were 242 youth with ASD who had recently exited the school system and were part of our larger longitudinal study; data were collected at five time points over nearly 10 years. Results indicated overall improvement of autism symptoms and internalized behaviors over the study period, but slowing rates of improvement after exit. Youth who did not have an intellectual disability evidenced the greatest slowing in improvement. Lower family income was associated with less improvement. Our findings suggest that adult day activities may not be as intellectually stimulating as educational activities in school, reflected by less phenotypic improvement after exit. PMID- 20361247 TI - Symptom dimensions in OCD: item-level factor analysis and heritability estimates. AB - To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions. PMID- 20361249 TI - Quality at the point of service: profiles of practice in after-school settings. AB - A unique observational data set was used to explore quality at the point of service in after-school programs. Staff practices in after-school settings were represented on a series of unidimensional scales closely indexed to staff behavior. In order to account for heterogeneity of staff performances, pattern centered methods were used to construct profiles of common staff practices. Results revealed six pedagogy profiles that were classified in terms of three broad types of performances delivered by after-school staff: (1) positive youth development, (2) staff-centered, and (3) low-quality. Staff membership in these profiles was not related to youth-staff ratio. However, results revealed significant differences between the profiles on the content of the offering and the age of youth in the setting. PMID- 20361248 TI - Robertsonian fusions, pericentromeric repeat organization and evolution: a case study within a highly polymorphic rodent species, Gerbillus nigeriae. AB - Pericentromeric repeats have been claimed to mediate centric fusions through heterologous recombination of arrays of tandemly repeated and highly homogenized motifs. However, mammalian case studies are essentially restricted to pathologic fusions in human, or to the house mouse Roberstonian (Rb) races. We here provide an example in a wild gerbil rodent, Gerbillus nigeriae, which displays an extensive Rb polymorphism, with 2n ranging between 2n = 60 and 74. The distribution of two closely related repeats, GERB1 and GERB2 that were previously isolated by Volobouev et al. (Chromosoma 104:252-259, 1995) in this African species, were investigated in the genomes of seven individuals with various diploid numbers. Our results clearly show that GERB1 and GERB2 are organized in a non-random manner, with GERB2 and GERB1 being clearly juxtacentromeric and centromeric, respectively. Finally, cloning and sequencing revealed that, unlike GERB2, GERB1 monomers display a more homogeneous organization at both the nucleotide and structural levels. Altogether, our results point toward a pivotal role of GERB1 repeats in the mediation of Rb fusions through heterologous recombination, with some evidence of subsequent loss of repeats after the Rb fusion during the course of evolution of metacentric elements. Moreover, the repeat pattern observed in G. nigeriae closely matches the organization and sequence structure of satellite DNAs described in human acrocentrics. Consequently, G. nigeriae appears as an additional model for the study of repeat evolution and its role in centric fusions and their consequences in mammals. PMID- 20361250 TI - Association of a TGF-beta1 gene -509 C/T polymorphism with breast cancer risk: a meta-analysis. AB - Transforming growth factor-beta1 (TGF-beta1) is negative regulator of cell proliferation and the cell cycle, and plasma levels of TGF-beta1 are twice as high in TGF-beta1 -509 T homozygotes as in -509 C homozygotes. Published studies on the association between the TGF-beta1 gene -509 C/T polymorphism and breast cancer risk are inconclusive, and a meta-analysis is required to verify the association. We performed a meta-analysis of four studies, including a total of 5,986 cases and 6,829 controls. Our pooled results indicate that the TGF-beta1 gene -509 C/T polymorphism is not associated with breast cancer risk in a TT versus CC codominant (OR = 1.08; 95% CI = 0.87-1.34; P = 0.494), in a CT versus CC codominant (OR = 1.02; 95% CI = 0.94-1.10; P = 0.686), recessive (OR = 0.92; 95% CI = 0.83-1.03; P = 0.157), and dominant (OR = 1.03; 95% CI = 0.96-1.11; P = 0.439) models. Conclusively, this meta-analysis suggests that the TGF-beta1 gene 509 T allele polymorphism does not decrease breast cancer risk. PMID- 20361252 TI - Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. AB - Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with anti-angiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0.4% in the single-arm study. There was a trend towards increased ONJ incidence in patients who received bisphosphonate therapy versus those with no bisphosphonate exposure (0.9 vs. 0.2%, respectively, in the pooled analysis of the randomised trials; 2.4 vs. 0%, respectively, in ATHENA). In conclusion, this is the largest analysis of ONJ in patients receiving bevacizumab for LR/MBC. The 0.3-0.4% incidence is considerably lower than previously suggested with anti-angiogenic therapy in a small retrospective analysis. The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management. The 0.9-2.4% incidence seen in bisphosphonate-exposed patients receiving bevacizumab is within the 1-6% range reported for bisphosphonates alone. Good oral hygiene, dental examination, and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of bevacizumab administration. PMID- 20361251 TI - Change in lifestyle behaviors and medication use after a diagnosis of ductal carcinoma in situ. AB - Women with ductal carcinoma in situ (DCIS) of the breast represent a growing cancer survivor population with a diagnosis of uncertain malignant potential. These survivors face an absence of scientific guidelines regarding lifestyle changes that can help to prevent a breast cancer recurrence. In this first report from the Wisconsin In Situ Cohort (WISC) study, we examine how women are currently changing their lifestyle behaviors and medication use following a diagnosis of DCIS. At study entry (1997-2006), 1,959 subjects (78% of eligible) with DCIS were identified from the Wisconsin cancer registry and administered an interview assessing behaviors prior to diagnosis. Follow-up interviews were completed every 2 years after the initial interview, beginning in 2003 and continuing through 2006. After adjusting for age and calendar year, women were 2.2 kg (95% CI 1.4, 3.0) heavier, 35% (95% CI 20, 47) less likely to be a smoker, 19% (95% CI -1, 43) more likely to use non-steroidal anti-inflammatory drugs, and 57% (95% CI 26, 95) more likely to use antidepressants after a DCIS diagnosis compared to 1 year prior to diagnosis. Use of postmenopausal hormones decreased sharply (OR = 0.06; 95% CI 0.04, 0.09) following a DCIS diagnosis. These findings indicate that women make substantial changes in their behaviors after a DCIS diagnosis. This cohort will be further monitored to evaluate the association between these behaviors and health outcomes following DCIS. PMID- 20361254 TI - Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. AB - Stroma tissue surrounding cancer cells plays an important role in tumor development and behavior. In colorectal cancer, it has been found that the amount of stroma within the primary tumor is of prognostic value. We therefore have evaluated the prognostic value of this tumor-stroma ratio for breast cancer. A cohort of 574 early breast cancer patients, primarily treated with surgery between 1985 and 1994 was analyzed for the tumor-stroma ratio. The percentage of stroma was visually estimated on Haematoxylin-Eosin (H&E) stained histological sections. Patients with more than 50% intra-tumor stroma were quantified as stroma rich and patients with less than 50% as stroma poor. For the total group of patients, stroma-rich tumors had a shorter relapse-free period (RFP) (P = 0.001) and overall survival (OS) (P = 0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (P < 0.001) and also in stratified analysis based on systemic treatment. Importantly, in the triple-negative cancer subpopulation, patients with stroma rich tumors had a 2.92 times higher risk of relapse (P = 0.006) compared to those with stroma-poor tumors, independently of other clinico-pathological parameters. Five-year RFP-rates for triple-negative cancer patients with stroma-rich compared to stroma-poor tumors were 56 and 81%, respectively. Tumor-stroma ratio has proven to be an independent prognostic factor for RFP in breast cancer patients and especially in the triple-negative cancer subpopulation. Tumor-stroma ratio could be easily implemented in routine daily pathology diagnostics, as it is simple to determine, reproducible, and performed in quick time. PMID- 20361253 TI - Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. AB - This randomized multicenter phase III trial evaluated the role of maintenance therapy with pegylated liposomal doxorubicin (PLD) after induction chemotherapy in patients with metastatic breast cancer (MBC). Patients without disease progression following first-line induction chemotherapy consisting of three cycles of doxorubicin (75 mg/m(2)) followed by three cycles of docetaxel (100 mg/m(2)) both every 21 days, were randomized to PLD (40 mg/m(2)) every 28 days for six cycles or to observation. Time to progression (TTP) was the primary endpoint. 288 patients were enrolled and received induction first-line chemotherapy. One hundred and fifty-five achieved response or stable disease and were randomized to maintenance PLD (n = 78) or observation (n = 77). With a median follow-up of 20 months from randomization (range 1-56), disease progression occurred in 94% of patients. PLD significantly improved TTP by 3.3 months (8.4 vs. 5.1 months; hazard ratio [HR] = 0.54, 95% CI: 0.39 to 0.76, P = 0.0002) compared with observation. Overall survival was not significantly prolonged with PLD (24.8 vs. 22.0 months, respectively; HR = 0.86, 95% CI: 0.58 1.27, P = 0.44). PLD-induced toxicity was mild and manageable with up to 5% of patients experiencing grade 3/4 non-hematologic events (fatigue, mucositis, palmar-plantar erythrodysesthesia). Grade 3/4 neutropenia occurred in 12% of patients; two patients developed febrile neutropenia. This phase III trial demonstrated that maintenance chemotherapy with PLD is well tolerated and offers improved TTP in patients with MBC following first-line chemotherapy. PMID- 20361255 TI - Zearalenone is bioactivated in the river Buffalo (Bubalus bubalis): hepatic biotransformation. AB - Zearalenone (ZEA) as a mycoestrogen is found frequently in human foods and animal feeds. Its estrogenic effects depend on its biotransformation fate including both first- and second-phase reactions, which are predominantly governed by hydroxylation and glucuronidation, respectively. In this study, we investigate the hepatic biotransformation of ZEA in river buffalo. To evaluate the hepatic biotransformation of ZEA, both subcellular fractions of the liver were prepared. ZEA was incubated with intracellular subfractions in the presence of nicotinamide dinucleotide phosphate, and the products were determined by means of high performance liquid chromatography. Moreover, in the same frame of experiment and in the presence of uridine diphosphate glucuronic acid, the rate of glucuronidation for substrate and products were estimated as well. We found that alpha-zearalenol (alpha-ZOL) is the major hydroxylated hepatic metabolite of ZEA produced by both studied subcellular fractions. The enzymatic kinetics analyses indicated that the alpha-ZOL and beta-ZOL production by microsomal fraction were two- and three-fold higher than those by postmitochondrial fraction, respectively. The calculated data showed that alpha-ZOL is conjugated with glucuronic acid more than ZEA and beta-ZOL, especially at the lower concentrations, which seems to be more applicable. Our data suggest that unlike other domestic ruminants including cattle and sheep, the hepatic biotransformation of ZEA in river buffalo results in bioactivation and formation of potent estrogenic metabolite. Moreover, at the relevant concentrations, the produced potent estrogenic metabolite is entirely conjugated with glucuronic acid and, consequently, may cause the prolongation of presence of the compound in the body due to enterohepatic cycle. PMID- 20361256 TI - Diversity of culturable actinobacteria from Qinghai-Tibet plateau, China. AB - To investigate the diversity of culturable actinobacteria and further screen for microbial pharmaceutics, seven different media were chosen to isolate actinobacteria from 87 soil samples collected from Qinghai-Tibet plateau. A total of 1930 strains was isolated and identified to belong to 11 suborders, i.e., Actinopolysporineae, Corynebacterineae, Frankineae, Glycomycineae, Kineosporiineae, Micrococcineae, Micromonosporineae, Propionibacterineae, Pseudonocardineae, Streptomycineae and Streptosporangineae, and 16 families, i.e., Nocardioidaceae, Actinopolysporaceae, Actinosynnemataceae, Dermacoccaceae, Geodermatophilaceae, Glycomycetaceae, Kineosporiaceae, Microbacteriaceae, Micromonosporaceae, Nocardiaceae, Promicromonosporaceae, Propionibacteriaceae, Pseudonocardiaceae, Streptomycetaceae, Streptosporangiaceae and Thermomonosporaceae. A primary taxonomic study showed that at least 22 genera of actinobacteria were identified from the soil samples, among which ten isolates represented hitherto unknown species. The results showed that there was abundant actinobacterial species diversity in the soil samples from the Qinghai-Tibet plateau. PMID- 20361257 TI - Comparative evaluation of automated ribotyping and RAPD-PCR for typing of Lactobacillus spp. occurring in dental caries. AB - A group of 67 Lactobacillus spp. strains containing Lactobacillus casei/paracasei, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus plantarum, Lactobacillus rhamnosus and Lactobacillus salivarius species isolated from early childhood caries and identified to the species level in a previous study (Svec et al., Folia Microbiol 54:53-58, 2009) was characterized by automated ribotyping performed by the RiboPrinter microbial characterization system and by randomly amplified polymorphic DNA fingerprinting (RAPD-PCR) with M13 primer to evaluate these techniques for characterization of lactobacilli associated with dental caries. Ribotyping revealed 55 riboprints among the analysed group. The automatic identification process performed by the RiboPrinter system identified 18 strains to the species level, however cluster analysis divided obtained ribotype patterns into individual clusters mostly corresponding to the species assignment of particular strains. RAPD-PCR fingerprints revealed by the individual Lactobacillus spp. showed higher variability than the ribotype patterns and the fingerprint profiles generated by the analysed species were distributed among one to four clusters. In conclusion, ribotyping is shown to be more convenient for the identification purposes while RAPD-PCR fingerprinting results indicate this method is a better tool for typing of Lactobacillus spp. strains occurring in dental caries. PMID- 20361258 TI - Geometrical confining effects in compression molding of co-continuous polymer blends. AB - Polymer blending is a versatile method for production of co-continuous porous materials. While numerous studies have been performed to elucidate the thermal annealing effects on the bulk structure, the effect of geometrical confinement is little understood. In the present work, possible effects from geometrical confinement during in-mold annealing were explored. A 50/50 wt.% poly (lactic acid)/polystyrene (PLA/PS) blend was compression molded and annealed between two parallel plates without being confined circumferentially during the compression molding process. Different conditions for geometrical confinement, including varied gap size and compression ratio (initial to final thickness ratio), as well as modified surface properties, were employed. The experimental results indicated that the gap size played a profound role in affecting the structural development; the phase size near the mold surface was smaller than away from the surface. The actual phase structure and the resulting gradient in pore size were further affected by the mold surface properties. Additionally, the compression ratio was found to affect the morphological development especially near the mold surface. At a high compression ratio, a thin layer of PLA was formed immediately during compression. The thickness of this layer either grew or reduced in size depending on the mold surface properties. Understanding of these geometrical confining effects and implementing them in processing may lead to the development of innovative porous materials. PMID- 20361259 TI - Partitioned fluid-solid coupling for cardiovascular blood flow: validation study of pressure-driven fluid-domain deformation. AB - The Karlsruhe Heart Model (KaHMo) is a patient-specific simulation tool for a three-dimensional blood flow evaluation inside the human heart. Whereas KaHMo MRT is based on geometry movement identified from MRT data, KaHMo FSI allows the consideration of structural properties and the analysis of FSI. Previous investigations by Oertel et al. have shown the ability of KaHMo to gain insight into different intra-ventricular fluid mechanics of both healthy and diseased hearts. However, the in vivo validation of the highly dynamic cavity flow pattern has been a challenging task in recent years. As a first step, the focus of this study is on an artificial ventricular experiment, derived from real heart anatomy. Fluid domain deformation and intra-ventricular flow dynamics are enforced by an outer surface pressure distribution. The pure geometrical representation of KaHMo MRT can now be complemented by constitutive properties, pressure forces, and interaction effects using KaHMo FSI's partitioned code coupling approach. For the first time, fluid domain deformation and intra ventricular flow of KaHMo FSI has been compared with experimental data. With a good overall agreement, the proof of KaHMo's validity represents an important step from feasibility study toward patient-specific analysis. PMID- 20361260 TI - Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery studies. AB - The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. To seek for in vitro BBB models that are more accessible than animals for investigating drug transport across the BBB, we compared four in vitro cultured cell models: endothelial monoculture (bEnd3 cell line), coculture of bEnd3 and primary rat astrocytes (coculture), coculture with collagen type I and IV mixture, and coculture with Matrigel. The expression of the BBB tight junction proteins in these in vitro models was assessed using RT-PCR and immunofluorescence. We also quantified the hydraulic conductivity (L (p)), transendothelial electrical resistance (TER) and diffusive solute permeability (P) of these models to three solutes: TAMRA, Dextran 10K and Dextran 70K. Our results show that L (p) and P of the endothelial monoculture and coculture models are not different from each other. Compared with in vivo permeability data from rat pial microvessels, P of the endothelial monoculture and coculture models are not significantly different from in vivo data for Dextran 70K, but they are 2-4 times higher for TAMRA and Dextran 10K. This suggests that the endothelial monoculture and all of the coculture models are fairly good models for studying the transport of relatively large solutes across the BBB. PMID- 20361261 TI - Angiotensin converting enzyme I/D, angiotensinogen M235T and AT1-R A/C1166 gene polymorphisms in patients with acromegaly. AB - Acromegaly is associated with increased morbidity and mortality related to cardiovascular disease. Hypertension is one of the most common cardiovascular risk factors in acromegalic patients. The aim of this study was to investigate association between the frequencies of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and the angiotensin II type 1 receptor (AT1-R) A/C1166 gene polymorphisms and some clinical parameters of acromegalic patients. Total of 33 acromegalic patients and 63 controls were enrolled to study. We determined the ACE I/D, AGT M235T and AT1-R A/C1166 gene polymorphisms. Serum insulin, glucose, triglyceride, HDL-cholesterol, LDL-cholesterol, growth hormone and Insulin-like growth factor I (IGF-I) levels of subjects were analyzed. The frequencies of ACE and M235T AGT genotype were not significantly different between control and patients. The distribution of AT1R A/C1166 genotypes was significantly different between patients and control subjects (P=0.016). None of the three ACE genotypes, DD, ID and II displayed significant difference in acromegalic patients. A significant difference in systolic blood pressure and the serum IGF-I levels among the three AGT genotype, MM, MT and TT genotypes was found in patient group. Individuals with MT genotypes had significantly higher serum IGF-I levels and systolic blood pressure than MM and TT genotype subjects, P<0.05. In addition, serum triglyceride and HDL levels differed significantly between MM and MT genotypes, P<0.05. However, systolic blood pressure of patients with CC genotypes was found to be significantly higher than AA genotypes individuals in acromegaly group, P<0.05. It can be said that the angiotensinogen MT and AT1R CC1166 genotype carriers may have more risk than other genotypes in the development of hypertension in acromegaly. PMID- 20361263 TI - Health-related quality of life in inflammatory bowel disease measured with the generic 15D instrument. AB - OBJECTIVES: In many surveys, inflammatory bowel disease (IBD) has been shown to have a negative impact on health-related quality of life (HRQoL), especially when the disease is active. The purpose of this study was to compare a disease specific HRQoL tool (Inflammatory Bowel Disease Questionnaire, IBDQ) and a generic HRQoL tool (15D) in a large cohort of IBD patients, to assess the ability of the 15D to detect differences in HRQoL between disease states and to compare the HRQoL of IBD patients with that of the general population. METHODS: The study population comprised 2,931 IBD patients over 18 picked from a national Social Insurance Institute register and from a patient organization register. The 15D data for the general population came from the National Health 2000 Health Examination Survey. RESULTS: For patients with IBD, the 15D tool was feasible and had good discriminatory power. The total 15D score was significantly higher among patients with less active disease estimated by frequency of IBD symptoms and was strongly correlated with total IBDQ score. The general population scored significantly higher than did the study subjects on most of the 15D dimensions. CONCLUSIONS: The 15D was a fast and easy-to-apply method for the examination of HRQoL in IBD patients. In addition to HRQoL studies it could be used in everyday practice as well. Patients with IBD have worse HRQoL than do gender- and age standardized controls. PMID- 20361262 TI - Novel SNPs of butyrophilin (BTN1A1) and milk fat globule epidermal growth factor (EGF) 8 (MFG-E8) are associated with milk traits in dairy goat. AB - Butyrophilin (BTN1A1) and milk fat globule epidermal growth factor (EGF) 8 (MFG E8) genes are both milk fat globule membrane proteins. BTN1A1 plays a key role in the secretion of milk lipid and production which has effects on performance traits, while the MFG-E8 is vital for the development of the mammary gland and phagocytic clearance of apoptotic cells. Therefore, BTN1A1 and MFG-E8 gene are candidate genes for quantitative traits in mammalian animals with respect to milk performance traits. The objective of this study is to investigate variations in goat BTN1A1 and MFG-E8 gene and analyze their associations with growth trait and milk performance. In this study, the goat BTN1A1 gene showed a novel single nucleotide polymorphism (SNP): XM_001494179:g.8659C>T, resulting in a missense mutation: CTT (Leu)>TTT (Phe) at position 377 aa of the BTN1A1 (526 aa); the goat MFG-E8 gene showed four novel SNPs: NC_007319: g.843delA, 6417delC, 14892T>C and 14996A>C, only the 14892T>C result in a synonymous mutation. The associations between genotypes and production traits were analyzed. Significant statistical results implied that HinfI locus of BTN1A1 gene is associated with milk fat yield (P=0.004), total solid (P=0.002), solid-non fat (P=0.018) and first milk yield (P=0.030). The DA and EcoRV loci of MFG-E8 gene are associated with milk fat yield (DA locus: P=0.000; EcoRV locus: P=0.033) and total solid (DA locus: P=0.002; EcoRV locus: P=0.015) in the Xinong Saanen dairy goat. PMID- 20361264 TI - RASSF1A polymorphism in familial breast cancer. AB - Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. PMID- 20361265 TI - Current challenges for the early clinical development of anticancer drugs in the era of molecularly targeted agents. AB - The emergence of molecularly targeted agents in oncology has not only revolutionized the care of cancer patients, but also changed the daily practice of medical oncologists. Molecularly targeted agents indeed often differ from traditional cytotoxic agents by their administration schedules and routes, their toxicity profiles, and/or the assessment of their antitumor activity. In addition, the observation that molecularly targeted agents sometimes have limited antitumor activity as single agents has led clinical investigators to combine molecularly targeted agents together or with cytotoxic agents. We review here the current challenges for the early clinical development of anticancer agents in the era of molecularly targeted agents. We focus on the choice of end points in phase I oncology clinical trials, as well as on the choice of dose escalation methods with an emphasis on available dose escalation methods for molecularly targeted agents and for combination trials. PMID- 20361266 TI - Molecular response prediction in gastrointestinal stromal tumors. AB - Gastrointestinal stromal tumors (GISTs) are rare tumors of mesenchymal origin that develop along the gastrointestinal tract. Over ten years ago, their management dramatically changed following the discovery of an activating mutation of the KIT oncogene, which led to the use of small molecule inhibitors to therapeutically target these mutant kinases. Patients with advanced GIST, who were once a subset of sarcoma with poor prognosis due to their lack of chemosensitivity, may now survive more than 5 years following treatment with tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM) and sunitinib malate (SU). After ten years of active clinical and preclinical research, it has become clear that, although relatively homogeneous compared to other solid malignancies, there is still some heterogeneity in GISTs and most notably in regard to response to therapy. Here, we review the current data regarding molecular prediction of response in this disease. PMID- 20361267 TI - Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. AB - It has been reported previously that electric pulses of sufficiently high voltage and short duration can permeabilize the membranes of various organelles inside living cells. In this article, we describe electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. The cells were exposed to short, high voltage electric pulses (from 1 to 20 pulses, 60 ns, 50 kV/cm, repetition frequency 1 kHz). We observed that 10 and 20 such pulses induced permeabilization of membranes of endocytotic vesicles, detected by release of lucifer yellow from the vesicles into the cytosol. Simultaneously, we detected uptake of propidium iodide through plasma membrane in the same cells. With higher number of pulses permeabilization of the membranes of endocytotic vesicles by pulses of given parameters is accompanied by permeabilization of plasma membrane. However, with lower number of pulses only permeabilization of the plasma membrane was detected. PMID- 20361268 TI - Thin and flexible active electrodes with shield for capacitive electrocardiogram measurement. AB - Capacitive electrocardiogram (ECG) measurement over clothing requires large electrodes that can remain in contact with curved body surfaces to increase the signal-to-noise ratio (SNR). In this article, we propose a new, thin, and flexible active electrode for use as a capacitive ECG measurement electrode. This electrode contains a shielding plate over its surface and it is extremely thin and can bend freely to cover larger body surfaces of the curve-shaped human torso. We evaluated the characteristics of flexible active electrodes under conditions of varying cloth thickness, electrode size, and contacting pressure. Electrodes of two sizes (45 and 12 cm(2)) were attached to a chest belt to measure the ECG from the human torso, and the results obtained for both the sizes were compared. Cloth thickness and electrode size showed a dominant effect on the SNR, whereas contacting pressure had almost no effect. The flexible active electrodes attached to chest belts wrapped closely and uniformly over the curved surface of the torso and SNR was increased with an increase in electrode size. Although the ECG signal became more distorted as the cloth thickness increased, the larger-sized flexible active electrode (45 cm(2)) showed less distortion than the smaller-sized one (12 cm(2)). PMID- 20361269 TI - Molecular dynamics and partitioning of di-tert-butyl nitroxide in stratum corneum membranes: effect of terpenes. AB - In this work, we have used electron paramagnetic resonance (EPR) spectroscopy of the small spin label di-tert-butyl nitroxide (DTBN), which partitions the aqueous and hydrocarbon phases, to study the interaction of the terpenes alpha-terpineol, 1,8-cineole, L(-)-carvone and (+)-limonene with the uppermost skin layer, the stratum corneum, and the membrane models of 1,2-dipalmitoyl-sn-glycero-3 phosphatidylcholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The EPR spectra indicated that the terpenes increase both the partition coefficient and the rotational correlation time of the spin labels in the stratum corneum membranes, whereas similar effects were observed in the DMPC and DPPC bilayers only at temperatures below the liquid-crystalline phase. The EPR parameter associated to probe polarity inside the membranes showed thermotropically induced changes, suggesting relocations of spin probe, which were dependent on the membrane phases. While the DMPC and DPPC bilayers showed abrupt changes in the partitioning and rotational correlation time parameters in the phase transitions, the SC membranes were characterized by slight changes in the total range of measured temperatures, presenting the greatest changes or membranes reorganizations in the temperature range of approximately 50 to approximately 74 degrees C. The results suggest that terpenes act as spacers, weakening the hydrogen-bonded network at the polar interface and thus fluidizing the stratum corneum lipids. PMID- 20361270 TI - Recommendations of community pharmacists and health food store employees regarding undiagnosed symptoms of diabetes. AB - BACKGROUND: Consumers may seek health advice from health food store employees (HFSEs) and pharmacists. Delays in the diagnosis of time-critical illnesses may increase the likelihood of morbidity, mortality and healthcare expenditures. OBJECTIVE: To describe the information provided by HFSEs and pharmacists for symptoms of undiagnosed Type 1 diabetes. DESIGN: A standardized actor portrayed a consumer with symptoms of Type 1 diabetes at eight community pharmacies and 12 health food stores (HFSs) in Pittsburgh, Pennsylvania, and Chapel Hill and Durham, North Carolina. He inquired about potential diagnoses, the need to see a physician, and product recommendations. SUBJECTS: The subjects included twelve HFSEs and eight licensed pharmacists. RESULTS: Four of eight (50%) pharmacists and two of 12 (17%) HFSEs mentioned diabetes as a potential diagnosis. Although six pharmacists recommended urgent physician follow-up, only two HFSEs did so; two HFSEs explicitly advised against a physician visit. One pharmacist recommended a product. Nine HFSEs recommended at least one product (monthly costs, range: $24.70-$209.96). CONCLUSIONS: Even when presented with classic symptoms of Type 1 diabetes, under-recognition of diabetes was common among HFSEs and community pharmacists. Delays in treatment present a health risk to consumers. Further research could confirm these results and inform educational interventions to improve diabetes recognition by both groups. PMID- 20361271 TI - Familial risk of cancer and knowledge and use of genetic testing. AB - BACKGROUND: Identification of genetic risk factors for common diseases, including cancer, highlights the importance of familial risk assessment. Little is known about patterns of familial cancer risk in the general population, or whether this risk is associated with knowledge and use of genetic testing. OBJECTIVE: To examine the distribution of familial cancer risk and its associations with genetic testing in the United States. DESIGN: Cross-sectional analysis of the 2005 National Health Interview Survey (NHIS). PARTICIPANTS: 31,428 adults who completed the NHIS Cancer Control Supplement. MAIN MEASURES: Familial cancer risk was estimated based on the number of first-degree relatives with a breast and ovarian cancer syndrome (BRCA)- or a Lynch-associated cancer, age of onset (<50 or > or = 50 years), and personal history of any cancer. Outcomes included having heard of genetic testing, discussed genetic testing with a physician, been advised by a physician to have testing, and received genetic testing. KEY RESULTS: Most adults (84.5%) had no family history of BRCA- or Lynch syndrome associated cancer; 12.9% had a single first-degree relative (5.3% with early onset); and 2.7% had > or = 2 first-degree relatives. Although 40.2% of adults had heard of genetic testing for cancer risk, only 5.6% of these individuals had discussed testing with a physician, and of these 36.9% were advised to be tested. Overall, only 1.4% of adults who had heard of genetic testing received a test. Familial risk was associated with higher rates of testing; 49.5% of participants in the highest risk group had heard of testing, of those 14.8% had discussed it with their physician, and 4.5% had received genetic testing. CONCLUSIONS: These nationally representative data provide estimates of the prevalence of familial cancer risk in the US and suggest that information about genetic testing is not reaching many at higher risk of inherited cancer. PMID- 20361272 TI - Faculty values. PMID- 20361273 TI - Hmgb1 promotes wound healing of 3T3 mouse fibroblasts via RAGE-dependent ERK1/2 activation. AB - HMGb1 is a nuclear protein playing a role in DNA architecture and transcription. This protein has also been shown to function as a cytokine and to stimulate keratinocyte scratch wound healing. Due to the importance of finding new wound healing molecules, we have studied the effects of HMGb1 on fibroblasts, another major skin cell type, using the NIH 3T3 line. HMGb1 expression in these cells was assessed by Western blot, while its nuclear localization was pointed out by confocal immunofluorescence. HMGb1-induced cell proliferation with a maximum at a concentration of 10 nM, and such a dose also stimulated cell migration and scratch wound healing. Western blot analysis showed that HMGb1 activates ERK1/2, while the use of an anti-RAGE receptor-blocking antibody and of the selective MEK1/2 inhibitor PD98059 blocked ERK1/2 activation and wound healing responses to HMGb1. Taken together data show that HMGb1 promotes 3T3 fibroblast wound healing by inducing cell proliferation and migration, and that this occurs through the activation of the RAGE/MEK/ERK pathway. In conclusion, HMGb1 seems a good candidate for the development of medical treatments to be used on chronic or severe wounds. PMID- 20361274 TI - Static magnetic fields inhibit proliferation and disperse subcellular localization of gamma complex protein3 in cultured C2C12 myoblast cells. AB - Magnetic fields may delay the rate of cell cycle progression, and there are reports that magnetic fields induce neurite outgrowth in cultured neuronal cells. To demonstrate whether magnetic field also effects on myoblast cells in cell growth, C2C12 cell lines were cultured and 2000G static magnetic field was applied. After 48 h of incubation, both the WST-1 assay (0.01 < P < 0.025, t test) and direct cell counting (P < 0.0005, t-test) showed that static magnetic fields inhibit the proliferation of cultured C2C12 cells. Immunocytochemistry for alpha and tubulin gamma complex protein (TUBA and GCP3) was made and applying a static magnetic field-dispersed tubulin GCP3 formation, a intracellular apparatus for tubulin structuring in cell division. This protein expression was not altered by western blot. This study indicates that applying a static magnetic field alters the subcellular localizing of GCP3, and may delay the cell growth in cultured C2C12 myoblast cells. PMID- 20361275 TI - Cellular dynamic simulator: an event driven molecular simulation environment for cellular physiology. AB - In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID- 20361276 TI - Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET. AB - OBJECTIVE: XR9576 (tariquidar) is an anthranilic acid derivative and potent P glycoprotein (P-gp) inhibitor. XR9576 has undergone phase I and II studies as combined chemotherapy against cancer. XR9576 has been developed as a useful therapeutic agent but not as a PET probe. We therefore developed [(11)C]XR9576 as a PET probe and assessed whether PET studies using [(11)C]XR9576 are a promising approach to assess P-gp function primarily. METHODS: We synthesized [(11)C]XR9576 by methylation of 7-O-desmethyl XR9576 with [(11)C]methyl iodide. In in vivo tissue distribution, the effects of co-injection with XR9576 on the uptake of [(11)C]XR9576 in mice were investigated. PET studies using [(11)C]XR9576 were performed in P-gp and/or Bcrp knockout mice as well as in wild-type mice. Metabolites of [(11)C]XR9576 were measured in the brain and plasma of mice. RESULTS: [(11)C]XR9576 was successfully synthesized with suitable radioactivity for injection as well as appropriate radiochemical purity and stability. In in vivo tissue distribution, the brain uptake of [(11)C]XR9576 significantly increased about tenfold of control on co-injection with >10 mg/kg of XR9576. In PET studies, the AUC(brain) ([0-60 min]) in P-gp and P-gp/Bcrp knockout mice was 2- and 11-fold higher than that in wild-type mice. [(11)C]XR9576 showed a high metabolic stability (>90% unchanged form) in the brain and plasma of mice 30 min after injection. These results suggest that a tracer amount of [(11)C]XR9576 behave as the P-gp and Bcrp substrate, and the increased brain uptake or AUC(brain) of [(11)C]XR9576 correlates with P-gp and Bcrp functions. CONCLUSIONS: PET studies using [(11)C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors. PMID- 20361277 TI - Outcome of pediatric patients with Langerhans cell histiocytosis treated with 2 chlorodeoxyadenosine: a nationwide survey in Japan. AB - The aim of this study was to assess the outcome of treatment with 2 chlorodeoxyadenosine (2-CdA) in pediatric patients with Langerhans cell histiocytosis (LCH) in Japan. We retrospectively identified 17 pediatric LCH patients treated with 2-CdA. All patients were refractory or reactivated cases who had been initially treated according to the JLSG-02 protocol of the Japan LCH study group. At initiation of 2-CdA therapy, 4 patients had primary refractory multisystem (MS) disease with risk organ (RO) involvement (MS+), 9 patients had reactivated MS disease [5 MS+ and 4 without RO involvement (MS-)], and the remaining 4 patients had refractory/reactivated multifocal bone disease (MFB). Treatment with 2-CdA (4-9 mg/m(2)/day) was administered on 2-5 consecutive days and repeated every 3-4 weeks for a period that ranged from 2 to 12 months. Four primary refractory patients were treated with 2-CdA combined with high dose of cytarabine. In MS+ patients, response to treatment was observed in 5 of the 9 patients. In MS-/MFB patients, 5 of the 8 patients showed response to treatment. In the patients who were primary refractory or had reactivation during initial chemotherapy, 4 of 10 patients showed good response. On the other hand, in the patients having reactivation while off therapy, 6 of 7 patients showed good response. These findings suggest that 2-CdA is effective for reactivated LCH while off therapy. PMID- 20361278 TI - Severe autoimmune neutropenia associated with acute autoimmune hepatitis. AB - A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm(3)), normal hemoglobin and mild thrombocytopenia (115000/mm(3)). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient's blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors. PMID- 20361279 TI - Editorial: What is varus or valgus knee alignment?: a call for a uniform radiographic classification. PMID- 20361280 TI - Improving web site performance using commercially available analytical tools. AB - BACKGROUND: It is easy to accurately measure web site usage and to quantify key parameters such as page views, site visits, and more complex variables using commercially available tools that analyze web site log files and search engine use. This information can be used strategically to guide the design or redesign of a web site (templates, look-and-feel, and navigation infrastructure) to improve overall usability. The data can also be used tactically to assess the popularity and use of new pages and modules that are added and to rectify problems that surface. QUESTIONS/PURPOSES: This paper describes software tools used to: (1) inventory search terms that lead to available content; (2) propose synonyms for commonly used search terms; (3) evaluate the effectiveness of calls to action; (4) conduct path analyses to targeted content. METHODS: The American Academy of Orthopaedic Surgeons (AAOS) uses SurfRay's Behavior Tracking software (Santa Clara CA, USA, and Copenhagen, Denmark) to capture and archive the search terms that have been entered into the site's Google Mini search engine. The AAOS also uses Unica's NetInsight program to analyze its web site log files. RESULTS: These tools provide the AAOS with information that quantifies how well its web sites are operating and insights for making improvements to them. CONCLUSIONS: Although it is easy to quantify many aspects of an association's web presence, it also takes human involvement to analyze the results and then recommend changes. Without a dedicated resource to do this, the work often is accomplished only sporadically and on an ad hoc basis. PMID- 20361281 TI - Insufficient bone regenerate after intramedullary femoral lengthening: risk factors and classification system. AB - BACKGROUND: Control of distraction rate with an intramedullary skeletal kinetic distractor (ISKD) may be problematic and a high distraction rate may result in insufficient bone regenerate. QUESTIONS/PURPOSES: Are distraction problems preventable when using the ISKD, and what are the risk factors for and radiologic types of insufficient bone regenerate during ISKD lengthening? PATIENTS AND METHODS: We analyzed 37 consecutive ISKD femoral lengthening procedures in 35 patients with a mean age 33 +/- 11 years and minimum followup of 12 months (average, 27 +/- 9 months; range, 12-55 months). The average length gain was 42.8 +/- 12.9 mm. RESULTS: Eight patients had problems during distraction: seven had "runaway nails" and one had a nondistracting nail. Insufficient bone regenerate developed in eight patients. Important risk factors were a distraction rate greater than 1.5 mm/day (9.1 times higher risk), age 30 years or older, smoking, and lengthening greater than 4 cm. Less important risk factors identified were creation of the osteotomy at the site of previous trauma or surgery and acute correction of associated deformities. We proposed a radiologic classification for failure of bone regeneration: partial regenerate failure (Type I) or complete failure resulting in a segmental defect subdivided according to a length of 3 cm or less (Type IIa) or greater than 3 cm (Type IIb). CONCLUSIONS: Distraction problems with the ISKD were related mostly to internal malfunction of the lengthening mechanism. A distraction rate greater than 1.5 mm/day should be avoided in femoral intramedullary lengthening. Smoking should be a contraindication for femoral lengthening. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20361282 TI - Bacterial colonization of bone allografts: establishment and effects of antibiotics. AB - BACKGROUND: Bone grafts are frequently used to supplement bone stock and to establish structural stability. However, graft-associated infection represents a challenging complication leading to increased patient morbidity and healthcare costs. QUESTIONS/PURPOSES: We therefore designed this study to (1) determine if increasing initial S. aureus inoculation of bone allograft results in a proportionate increase in colonization; (2) assess if antibiotics decrease colonization and if antibiotic tethering to allograft alters its ability to prevent bacterial colonization; and (3) determine if covalent modification alters the allograft topography or its biological properties. METHODS: Allograft bone and vancomycin-modified bone (VAN-bone) was challenged with different doses of S. aureus for times out to 24 hours in the presence or absence of solution vancomycin. Bacterial colonization was assessed by fluorescence, scanning electron microscopy (SEM), and by direct colony counting. Cell density and distribution of osteoblast-like cells on control and modified allograft were then compared. RESULTS: Bacterial attachment was apparent within 6 hours with colonization and biofilm formation increasing with time and dose. Solution vancomycin failed to prevent bacterial attachment whereas VAN-bone successfully resisted colonization. The allograft modification did not affect the attachment and distribution of osteoblast-like cells. CONCLUSIONS: Allograft bone was readily colonized by S. aureus and covered by a biofilm with especially florid growth in natural topographic niches. Using a novel covalent modification, allograft bone was able to resist colonization by organisms while retaining the ability to allow adhesion of osteoblastic cells. CLINICAL RELEVANCE: Generation of allograft bone that can resist infection in vivo would be important in addressing one of the most challenging problems associated with the use of allograft, namely infection. PMID- 20361283 TI - The classic: On the antiseptic principle in the practice of surgery. 1867. AB - This Classic Article is a reprint of the original work by Baron Joseph Lister, On the Antiseptic Principle in the Practice of Surgery. An accompanying biographical sketch of Baron Joseph Lister is available at DOI 10.1007/s11999-010-1319-3 . The Classic Article is (c)1867 and is reprinted with courtesy from Lister J. On the antiseptic principle in the practice of surgery. Br Med J. 1867;ii:246. PMID- 20361284 TI - The psychosocial oncology learning assessment: a province-wide survey of cancer care providers' learning needs. AB - A psychosocial oncology learning needs assessment was developed and offered online to cancer care providers in a variety of settings across all health regions in British Columbia. The purpose was to better understand the psychosocial learning needs of cancer care providers and to use this knowledge to shape continuing education priorities. Respondents' preferred learning formats, access to technology and barriers to accessing psychosocial learning opportunities were also assessed. Cancer care providers including radiation therapists, social workers, dieticians, pharmacists, physicians and nurses in both community and agency settings were surveyed. Two hundred and sixty-seven people completed the survey. Key learning needs identified included cultural aspects of care, symptom management, treating the anxious patient, self-care for the professional, care of elderly patients, basic cancer-related medical issues surrounding care and ethics. Community respondents indicated more needs than agency respondents. On-site training was the most preferred learning format, and time constraints were the biggest barrier to accessing learning opportunities. Participants had access to technology. Next steps include conducting key informant and focus group interviews to determine if interest in a learning need is the same as a relevant knowledge and practice gap. This research suggests that cancer care providers are interested in learning more about the psychosocial issues related to cancer care. PMID- 20361285 TI - The influence of the UV-index on attitudes toward sun exposure in the German population. AB - The increased skin cancer incidences are important public health problems. In spite of the strong promotion of the UV-index as essential UV risk education tool, only few studies have investigated peoples understanding of the UV-index. This paper is the first to present representative data on UV-index understanding in Germany. In 2007, a representative telephone survey was carried out among 1,501 German residents aged 14 years and older. Only 27% of the respondents had heard of the UV-index before and 17% of the German respondents claimed to consider the index for their sun habits. Less than 10% of the German population was able to attribute the correct meaning to the UV-index as well as know their own skin type. The results of the present study suggest that informing the public about the UV-index has very limited impact on the public's understanding of the UV-index as well as on their attitude toward sun exposure. The results warrant the question whether the UV-index in the present form is a useful education tool in UV risk communication. PMID- 20361286 TI - Tumor markers AFP, CA 125, and CA 19-9 in the long-term follow-up of sacrococcygeal teratomas in infancy and childhood. AB - Given the tendency of a proportion of sacrococcygeal teratomas (SCT) to recur, we evaluated whether serial tumor marker measurements are helpful in the management of these children. Between 1985 and 2006, 32 children with SCT were followed up for 1-15 years, and a total of 344, 197, and 193 serial samples for serum alpha fetoprotein (AFP), CA 125, and CA 19-9 were analyzed, respectively. Six children with neonatal SCT developed eight recurrences. Serum AFP was elevated in two of two children prior to diagnosis of malignant recurrences (yolk sac tumor and adenocarcinoma), and CA 125 was elevated in one third of mature and one third of immature recurrences. CA 19-9 remained within reference values in relation to recurrences of neonatal SCT. Taken together, serum CA 125 measurements may complement the use of serum AFP in the follow-up of SCT. PMID- 20361287 TI - Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value. AB - Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p < 0.0001). CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER-) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer. PMID- 20361288 TI - Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma. AB - Collagen XVIII is a component of vascular and epithelial basement membranes. The C-terminal fragment of the protein is termed endostatin, and is a potent inhibitor of angiogenesis. No reports on the clinical implications of collagen XVIII expression in human gastric cancer are currently available. Here, we investigate the clinical significance of collagen XVIII expression in gastric cancer. Seven gastric cancer cell lines were subjected to Western blotting. Collagen XVIII expression was examined in 118 gastric carcinoma tissues via immunohistochemistry. Western blotting revealed the presence of the 22-kDa collagen XVIII protein in four of seven gastric cancer cell lines. Immunohistochemistry detected collagen XVIII expression in the tumor cytoplasm in 115 of 118 gastric carcinoma patients (97%). No correlation was evident between collagen XVIII expression score and clinicopathologic findings when all patients were considered together. However, on subgroup analysis, 42 of 70 patients with distant metastasis were classified into low or moderate collagen XVIII expression groups, whereas the remaining 28 patients were grouped as showing high collagen XVIII expression. The prognosis for patients with high collagen XVIII-expressing gastric carcinoma was significantly worse than that for patients displaying low or moderate collagen XVIII expression (median survival time, 7.8 months vs. 18.3 months [log-rank, p = 0.01]; median time to progression, 3 months vs. 8 months [log-rank, p = 0.01]). High expression of collagen XVIII is associated with poor prognosis in patients with metastatic gastric carcinoma. Further studies on larger patient populations are warranted to validate the utility of collagen XVIII as a prognostic biomarker in gastric carcinoma. PMID- 20361289 TI - Overexpression of aldehyde dehydrogenase-2 attenuates neurotoxicity induced by 4 hydroxynonenal in cultured primary hippocampal neurons. AB - 4-Hydroxynonenal (4HNE) is a toxic aldehyde which can accumulate during neurodegenerative diseases, such as AD. 4HNE-induced neuronal cytotoxicity includes the damage of neurite growth as well as a potential threat leading to the neuronal cell death. This study was designed to examine whether overexpression of aldehyde dehydrogenase-2 (ALDH2) affects 4HNE-induced neurite outgrowth blockage and neuronal death in primary hippocampal neurons in vitro. Plasmid-encoding rat ALDH2 was constructed and transfected into cultured rat hippocampal neurons. In vitro-cultured rat hippocampal neurons with the transfection of ALDH2 gene were showing resistance to 4HNE-induced neurite damage. Overexpression of ALDH2 in cultured rat hippocampal neurons blocked 4HNE induced (3.2 MUM for 24 h) reduction of neurite outgrowth and branching. In addition to the effect on neurite growth, ALDH2 overexpression also can protect neurons from 4HNE-evoked (10 MUM for 24 h) neuronal death. Furthermore, we found that overexpression of ALDH2 can decrease the caspase-3 protein expression level; at the same time, it can decrease the reactive oxygen species (ROS) level and the disruption of mitochondrial transmembrane potential in cultured hippocampal neurons. Our data suggested that overexpressed ALDH2 gene may moderate 4HNE induced neuronal death by regulating caspase-3 protein and ROS level in cultured hippocampal neurons. Based on these findings, ALDH2 gene can be a potential therapeutic target for treatment of neurodegenerative diseases, such as AD. PMID- 20361290 TI - Inhibition of hydrogen sulfide generation contributes to 1-methy-4 phenylpyridinium ion-induced neurotoxicity. AB - Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of 1-methy-4-phenylpyridinium ion (MPP(+)). Increasing studies have shown that hydrogen sulfide (H(2)S) is an endogenous antioxidant gas. We have hypothesized that MPP(+)-caused neurotoxicity may involve the imbalance of proportion to this endogenous protective antioxidant gas. The aim of this study is to evaluate whether MPP(+) disturbs H(2)S synthesis in PC12 cells, a clonal rat pheochromocytoma cell line, and whether disturbance of H(2)S generation induced by MPP(+) is an underlying mechanism of MPP(+)-induced neurotoxicity. We show that exposure of PC12 cells to MPP(+) causes a significant decrease in H(2)S generation and results in remarkable cell damage. We find that cystathionine-beta synthetase (CBS) is catalyzed in PC12 cells to generate H(2)S, and that both expression and activity of CBS are inhibited by MPP(+) treatment. Exposure of sodium hydrosulfide (NaHS), a donor of H(2)S, extenuates MPP(+)-induced cytotoxicity and ROS accumulation in PC12 cells, while inhibition of CBS by amino oxyacetate (AOAA) exacerbates the effects of MPP(+). These results indicate that MPP(+) neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS. This study provides novel insights into cell death observed in neurodegenerative disease such as Parkinson's disease. PMID- 20361292 TI - Development and validation of a screening assay for the evaluation of putative neuroprotective agents in the treatment of Parkinson's disease. AB - Following initial diagnosis of Parkinson's disease, if it were possible to prescribe a treatment that could halt or prevent further neurodegeneration, disease progression could be prevented. The aim of this study was to generate a quick and reliable assay for assessing putative neuroprotective agents for parkinsonian patients. Abnormalities in mitochondria, proteasome and lysosome function, as well as oxidative stress cause cell death in Parkinson's disease. Thus, we exposed neuroblastoma (SH-SY5Y) cells to EC(50) of toxins that mimic these cell death mechanisms (dopamine to induce oxidative stress; naphthazarin to inhibit lysosome function; proteasome inhibitor N-carbobenzyloxy-Ile-Glu(O-t butyl)-Ala-leucinal (PSI) to inhibit the UPS (ubiquitin proteasome system) and rotenone to inhibit mitochondria function) in the presence of five compounds previously chosen as neuroprotective agents, and assessed cell viability. Coenzyme Q10 (117 MUM) significantly protected against four toxins, dopamine: 16.3 +/- 3.3%; naphthazarin: 10.8 +/- 1.1%; PSI: 16.2 +/- 2.9%; rotenone: 53.2 +/ 4.2%; whereas caffeine (140 MUM), creatine (25 mM), nicotine (1 MUM) and deprenyl (10 MUM) provided protection against some, but not all toxins. Interestingly, coenzyme Q10 is the only compound out of the five that showed neuroprotective potential in clinical trials. Thus, there is a direct correlation between the success of disease modifying agents in the clinic and their ability to protect against multiple cell death mechanisms in this assay. We propose that exposure of SH-SY5Y cells to different toxins that recapitulate cell death mechanisms in Parkinson's disease serves as a rapid and reliable method to test neuroprotective agents that may succeed in clinical trials. PMID- 20361293 TI - Blood-brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome. AB - Cerebral hyperperfusion syndrome (CHS) may occur as a severe complication following surgical treatment of carotid stenosis. However, the mechanism inducing neurological symptoms in CHS remains unknown. We describe a patient with CHS presenting with seizures 24 h following carotid endarterectomy. Imaging demonstrated early ipsilateral blood-brain barrier (BBB) breakdown with electroencephalographic evidence of cortical dysfunction preceding brain edema. Using in vitro experiments on rat cortical tissue, we show that direct exposure of isolated brain slices to a serum-like medium induces spontaneous epileptiform activity, and that neuronal dysfunction is triggered by albumin. We propose BBB breakdown and subsequent albumin extravasation as a novel pathogenic mechanism underlying CHS and a potential target for therapy. PMID- 20361291 TI - Regulation of AMPA receptor trafficking in the nucleus accumbens by dopamine and cocaine. AB - Nucleus accumbens (NAc) neurons are excited primarily by AMPA-type glutamate receptors (AMPAR). This is required for cocaine seeking in animal models of cocaine addiction, suggesting AMPAR transmission in the NAc as a key control point for cocaine-related behaviors. This review will briefly describe AMPAR properties and trafficking, with a focus on studies in NAc neurons, and then consider mechanisms by which cocaine may alter AMPAR transmission. Two examples will be discussed that may be important in two different stages of addiction: learning about drugs and drug-related cues during the period of drug exposure, and persistent vulnerability to craving and relapse after abstinence is achieved. The first example is drawn from studies of cultured NAc neurons. Elevation of dopamine levels (as would occur following cocaine exposure) facilitates activity dependent strengthening of excitatory synapses onto medium spiny neurons, the main cell type and projection neuron of the NAc. This occurs because activation of D1-class dopamine receptors primes AMPAR for synaptic insertion. This may create a temporal window in which stimuli related to cocaine-taking are more efficacious at eliciting synaptic plasticity and thus being encoded into memory. The second example involves rat models of cocaine addiction. Cell surface and synaptic expression of AMPAR on NAc neurons is persistently increased after withdrawal from repeated cocaine exposure. We hypothesize that this increases the reactivity of NAc neurons to glutamate inputs from cortex and limbic structures, facilitating the ability of these inputs to trigger cocaine seeking and thus contributing to the persistent vulnerability to relapse that characterizes addiction. PMID- 20361294 TI - Motor-dominant chronic inflammatory demyelinating polyneuropathy. AB - We reviewed the clinical, electrophysiological an laboratory findings, plus the therapeutics and evolution of patients with motor-dominant Chronic inflammatory demyelinating polyneuropathy (CIDP) and compared them with those of other CIDP patients. Among 12 consecutive CIDP patients, we identified five patients with motor-dominant CIDP. The five patients with motor-dominant CIDP initially presented with weakness of the upper limbs. Cervical magnetic resonance imaging (MRI) examinations of the patients with motor-dominant CIDP showed that the most affected lesions are the cervical nerve roots and brachial plexus. The clinical course of these patients was relapsing-remitting, and they improved markedly after treatment by intravenous immunoglobulin (IVIg) infusion or plasmapheresis. However, they did not improve in response to corticosteroid therapy during the acute phase of relapses. The relapses frequently occurred within 2 years, but rarely occurred after that. The score in the modified Rankin disability scale (mRDS) at the last follow-up period was statistically lower for the patients with motor-dominant CIDP than for the other CIDP patients (P < 0.002). The characteristic clinical features, responsiveness to treatment, and prognosis suggest that motor-dominant CIDP is a distinct subtype of CIDP, with a specific immunological background. Repeated IVIg therapy is required to maintain the motor functions of patients with motor-dominant CIDP. We consider that treatment for recurrence prevention as an alternative to IVIg therapy is very important for patients with motor-dominant CIDP. PMID- 20361296 TI - This Month in APR. PMID- 20361295 TI - How predictive is the MMSE for cognitive performance after stroke? AB - Cognitive deficits are commonly observed in stroke patients. Neuropsychological testing is time-consuming and not easy to administer after hospital discharge. Standardised screening measures are desirable. The Mini-Mental State Examination (MMSE) is the test most widely applied to screen for cognitive deficits. Despite its broad use, its predictive characteristics after stroke have not been exhaustively investigated. The aim of this study was to determine whether the MMSE is able to adequately screen for cognitive impairment and dementia after stroke and whether or not the MMSE can predict further deterioration or recovery in cognitive function over time. To this end, we studied 194 first-ever stroke patients without pre-stroke cognitive deterioration who underwent MMSEs and neuropsychological test batteries at 1, 6, 12, and 24 months after stroke. The MMSE score 1 month after stroke predicted cognitive functioning at later follow up visits. It could not predict deterioration or improvement in cognitive functioning over time. The cut-off score in the screening for 1 cognitive disturbed domain was 27/28 with a sensitivity of 0.72. The cut-off score in the screening for at least 4 impaired domains and dementia were 26/27 and 23/24 with a sensitivity of 0.82 and 0.96, respectively. The results indicated that the MMSE has modest qualities in screening for mild cognitive disturbances and is adequate in screening for moderate cognitive deficits or dementia in stroke patients 1 month after stroke. Poor performance on the MMSE is predictive for cognitive impairment in the long term. However, it cannot be used to predict further cognitive deterioration or improvement over time. PMID- 20361297 TI - Recent advances in transdermal drug delivery. AB - Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, due to the requirements that the patch area should be small enough for the patients to feel comfortable, and to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied. The development of an effective transdermal delivery system is dictated by the unique physicochemical property each drug molecule possesses. In this review, we have summarized various physical and chemical approaches for transdermal flux enhancement, including the application of electricity, ultrasound, microneedle and chemical enhancers. Pressure sensitive adhesive such as acrylics, rubbers and silicones are described together with recent developments. Factors affecting dosage form design, particularly for drug in adhesive system, like adhesion and crystallization are also discussed. PMID- 20361298 TI - Antidiabetic effect of flavones from Cirsium japonicum DC in diabetic rats. AB - Cirsium japonicum DC is a traditional Chinese herb used along with other herbs to treat hypertension, traumatic hemorrhage, inflammation, and renal cellular injury. Here, we isolated two flavones from Cirsium japonicum DC, pectolinarin and 5,7-dihydroxy-6,4'-dimethoxy flavone (DDMF), and investigated their antidiabetic effect in diabetic rats established by intravenous injection with streptozotocin followed by feeding with high-carbohydrate/high-fat diet. Both pectolinarin and DDMF showed antidiabetic effect in diabetic rats. However, FECJ, a mixture of pectolinarin and DDMF, is more effective than pectolinarin and DDMF in improving the plasma glucose, cholesterol and triglycerides levels in diabetic rats. The altered activities of glucose metabolism-related enzymes in diabetic rats were well reversed after flavone treatment. The plasma adiponectin level was greatly increased in diabetic rats treated with FECJ, while no obvious effect of the flavones on the dysregulated plasma insulin level and expressions of leptin and glucose transporter 4 (GLUT4) was observed. Our data indicated that the flavones improved adiponectin expression, accompanied by restoring of the dysregulated activities of the glucose metabolism-related enzymes, ultimately resulting in well improved glucose and lipid homeostasis. Thus, an antidiabetic effect of Cirsium japonicum DC was revealed in diabetic rats, suggesting the potential benefit of the Cirsium japonicum DC as an alternative in treating diabetes mellitus. PMID- 20361299 TI - An anti-influenza component of the bark of Alnus japonica. AB - This study to identify anti-influenza components of the bark of Alnus japonica resulted in the isolation of four lupane-type triterpenes (1-4) and one steroid (5). Their structures were characterized on the basis of physicochemical properties, NMR evidence, and ESI-MS data compared with reported data in the literature. Betulinic aldehyde (3) exhibited a particularly strong anti-influenza effect against KBNP-0028 relative to a positive control. PMID- 20361300 TI - Two acetylated megastigmane glycosides from the leaves of Ilex paraguariensis. AB - Two acetylated megastigmane glycosides, matenosides A (1) and B (2), have been isolated from the MeOH extract of Ilex paraguariensis leaves, and their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 exhibited human neutrophil elastase (HNE) inhibitory activity with IC(50) values of 50.4 muM and 11.1 microM, respectively. PMID- 20361301 TI - Cyclohexene, diketopiperazine, lactone and phenol derivatives from the sea fan derived fungi Nigrospora sp. PSU-F11 and PSU-F12. AB - Nigrosporanenes A (1) and B (2), two new cylohexene derivatives, and tyrosol (3) were isolated from the sea fan-derived fungus Nigrospora sp. PSU-F11, whereas five known compounds: 4-hydroxybenzoic acid (4), aplysiopsene D (5), 3 isochromanone (6), (-)-drimenin (7) and diketopiperazine derivative (8), were obtained from the fungus Nigrospora sp. PSU-F12. Their structures were established by spectroscopic evidence. We also tested their cytotoxic (on African green monkey kidney fibroblast and breast cancer cells), antioxidant (in the DPPH assay), and antibacterial (against the standard Staphylococcus aureus ATCC 25923 and methicillinresistant S. aureus) activities. PMID- 20361302 TI - Naphthoquinones from Catalpa ovata and their inhibitory effects on the production of nitric oxide. AB - Bioassay-guided fractionation of a CH2Cl2-soluble fraction of the stems of Catalpa ovata led to isolation of a new naphthoquinone, 4-hydroxy-2-(2-methoxy-3 hydroxy-3-methyl-but-1-enyl)-4-hydro-1H-naphthalen-1-one (10), together with nine known compounds, catalponol (1), catalponone (2), catalpalactone (3), alpha lapachone (4), 9-hydroxy-alpha-lapachone (5), 4,9-dihydroxy-alpha-lapachone (6), 9-methoxy-alpha-lapachone (7), 4-oxo-alpha-lapachone (8), and 9-methoxy-4-oxo alpha-lapachone (9). The structures were elucidated on the basis of spectroscopic analyses. The inhibitory effects of these isolates on lipopolysaccharide-induced NO synthesis in RAW 264.7 cells were evaluated. Among them, catapalactone (3), 9 hydroxy-alpha-lapachone (5) and 4,9-dihydroxy-alpha-lapachone (6) exhibited potent inhibitory effects, with IC(50) values of 9.80, 4.64 and 2.73 microM, respectively. PMID- 20361303 TI - The protective effects of paclitaxel on platelet aggregation through the inhibition of thromboxane A2 synthase. AB - Paclitaxel is an anticancer drug used in the treatment of ovarian, breast, head and neck, lung, and prostate cancer. We investigated the antiplatelet activity of paclitaxel in vitro as well as a possible antiplatelet mechanism. Paclitaxel inhibited washed rabbit platelet aggregation induced by collagen in a concentration dependent manner, with an IC(50) of 59.7 +/- 3.5. However, it had little effect on platelet aggregation mediated by arachidonic acid, U46619, a thromboxane (TX) A(2) mimic, or thrombin, suggesting that paclitaxel may strongly inhibit collagen mediated signal transduction. In accordance with these findings, paclitaxel blocked collagen induced cytosolic calcium mobilization, arachidonic acid liberation, and serotonin secretion. In addition, it inhibited arachidonic acid mediated platelet aggregation by about 37% by interfering with TXA(2) synthase as measured by the formation of arachidonic acid mediated TXA(2) and prostaglandin D(2), as well as cyclooxygenase-1 and TXA(2) synthase activity assays. Taken together, these results point to a cellular mechanism for the antiplatelet activity of paclitaxel through the inhibition of TXA(2) synthase and cytosolic calcium mobilization. This may contribute to the beneficial effects of paclitaxel on the cardiovascular system. PMID- 20361304 TI - Individual and interacting effects of formulation variables on the tensile strength and microbial survival in diclofenac tablets. AB - A work has been done to study the individual and interacting effects of formulation variables, using a 23 fractional factorial design. The effects of five variables, namely, relative density of tablets, nature and concentration of binder, compression process, and compression speed on the tensile strength and percent survival of Bacillus subtilis spores in diclofenac tablet formulations were determined. The effects of these variables were studied both singly and when they interact with each other in two fractional designs (Woolfall, 1964). The first fraction comprised of nature (N) and concentration (C) of binder, and relative density of tablets (D) while in the second fraction, compression speed (S), compression process (P) and relative density of tablets (D) were studied. In the first fraction, concentration of binder had the highest effect on tensile strength with the ranking C > D > N for both DCS (formulation containing Corn starch) and DDCP (formulation containing DCP), and C > N > D for DL (formulation containing Lactose). On the percent survival of Bacillus subtilis, relative density of tablets showed the highest effect with the ranking D > C > N for both DCS and DL, and D > N > C for DDCP. In the second fraction, compression speed generally had a great effect on both tensile strength and percent survival in all the formulations. The results of interactions among the variables showed the highest effect on tensile strength from interaction between concentration of binder and relative density of tablets (C-D) while interaction between compression speed and relative density of tablets (S-D) had the highest effect on percent survival in all the formulations. A fractional factorial design proved suitable in determining the magnitude of both the individual and interacting effects of the variables. The study showed that each of these variables has to be properly considered in producing tablets of satisfactory strength and reduced microbial survival. PMID- 20361305 TI - Formulation and evaluation of a gastroretentive dosage form of labetalol hydrochloride. AB - Labetalol hydrochloride (LBT), 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3 phenylpropyl) amino] ethyl]-benzamide, a non-selective alpha, beta-adrenoceptor antagonist is used in the treatment of hypertension. It shows variable bioavailability ranging from 10-80% which may be attributed to its minimum solubility in pH range 6 to 10, the pH conditions prevailing at the major site of absorption i.e. small intestine. Also due to its half life of 3 to 6 hrs it is administered twice daily. In the present work non-effervescent sustained release gastroretentive floating tablets of labetalol hydrochloride have been developed using various grades of HPMC and Poloxamer M127 as wetting agent. The tablets were evaluated for in vitro drug release, floating time, floating lag time, swelling studies etc. The tablets formulated with HPMC K4M CR and HPMC K15M CR along with Poloxamer showed negligible floating lag time with a total floating time over 12 hrs with complete release. Formulation was optimized using Stat-Ease Design Expert 7.1 software. Optimized batch was evaluated for the effect of change of osmolarity and pH on drug release, floating and swelling behaviour. PMID- 20361306 TI - Comparison of insulin sensitivity, glucose sensitivity, and first phase insulin secretion in patients treated with repaglinide or gliclazide. AB - The traditional sulfonylureas with long half-lives have sustained stimulatory effects on insulin secretion compared to the short-acting insulin secretagogue. In this study, we used the frequently sampled intravenous glucose tolerance test (FSIGT) to evaluate the insulin sensitivity (IS), glucose sensitivity (SG), and acute insulin response after glucose load (AIRg) after 4 months treatment with either gliclazide or repaglinide. The design of study was randomizedcrossover. We enrolled 20 patients with new-onset type 2 diabetes (mean age, 49.3 years). Totally three FSIGTs were performed, one before and one after each of the two treatment periods as aforementioned. No significant differences in fasting plasma glucose, insulin, body mass index, blood pressure, glycated hemoglobin, or lipids were noted between the two treatments. After the repaglinide treatment, higher AIRg, lower IS, and lower SG were noted, but they did not reach statistical significance. The disposal index (DI) was also not significantly different between the two treatments. In conclusion, since non-significantly higher DI, AIRg, lower IS and SG were noted after repaglinide treatment, it might be a better treatment for diabetes, relative to gliclazide. PMID- 20361307 TI - Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein. AB - Self-nanoemulsifying drug delivery system (SNEDDS) containing oil (Phosal 53 MCT), surfactant (Labrasol), and cosurfactant (Transcutol-HP or Lutrol-E400) was prepared to enhance solubility and dissolution of lutein. Ternary phase diagram of the SNEDDS was constructed to identify the self-emulsifying regions following which the percentage of oil, surfactant, and cosurfactant in the SNEDDS were optimized in terms of emulsification time and mean emulsion droplet size. The optimized SNEDDS consists of 25% oil, 60% surfactant, and 15% cosurfactant. When measured using USP XXIII dissolution apparatus II, the emulsification time of the SNEDDS prepared with Transcutol-HP as cosurfactant was less than 20 sec, and it was 20-30 sec in the SNEDDS prepared with Lutrol-E400. Mean emulsion droplet size was slightly smaller when Transcutol-HP was used as cosurfactant (80 +/- 6 nm), compared to when Lutrol- E400 was used (93 +/- 6 nm). Dissolution of lutein from the solid SNEDDS (physical mixture of the optimized SNEDDS and Aerosil 200) took place immediately (less than 5 min) in distilled water, and, once dissolved, no precipitation or aggregation of the drug were observed. In contrast, no drug was released from lutein powder or from the commercial product (Eyelac(R)) until 3 h of the study duration. PMID- 20361308 TI - In vitro / in vivo evaluation of NCDS-micro-fabricated biodegradable implant. AB - Using the nano-composite deposition system (NCDS) as a microfabrication technique, implantable scaffolds were prepared with poly(DL-lactide-co glycolide)(85:15) [PLGA(85:15)] as a biodegradable polymer. 5-Fluorouracil (5-FU) was used as a model drug, and hydroxyapatite (HA) was incorporated as a release modifier. In vitro drug release was evaluated and we confirmed that HA could control the release of drug from the prepared scaffolds, especially in the initial phase of the release. Furthermore, in vivo tests demonstrated that the microfabricated scaffold with pores was useful in reducing immune response and maintained its original shape, indicating that the drug delivery system was highly biocompatible. PMID- 20361310 TI - Polymer blends used to prepare nifedipine loaded hollow microspheres for a floating-type oral drug delivery system: in vitro evaluation. AB - The aim of this study was to investigate whether hollow microspheres prepared from polymer blends of polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC) could improve the vitro release behavior of the poorly water-soluble drug nifedipine. Hollow microspheres containing nifedipine were prepared by a solvent diffusion evaporation method using various ratios of PVP and EC codissolved with drug in ethanol/ether (5:1, v/v). The hollow microspheres could float in release medium for more than 24 h, and floating capacities were not be influenced by mixing PVP. In vitro release profiles of hollow microspheres prepared using EC along showed an initial burst release to some extent, and the cumulative release percentage was less than 55% after 24 h. But, not only the slope but also the shape of the release curves was affected by using mixture of PVP and EC. What's more important, when the ratio (PVP/EC) increased to 1.5:8.5, the cumulative release percentage could be increased to 95.8%. Furthermore, the release rate of microspheres showed a zero order approximate dynamic model and could be expressed by the following equation: Q=3.78t+8.52 (r=0.990). Consequently, hollow microspheres prepared using polymer blends of PVP and EC (1.5:8.5, w/w) could be suitable for floating-type controlled-release delivery systems for the oral administration of nifedipine. PMID- 20361309 TI - Selective inhibition of activated stellate cells and protection from carbon tetrachloride-induced liver injury in rats by a new PPARgamma agonist KR62776. AB - Activated hepatic stellate cells (HSC) are the primary source of extracellular matrix proteins found in liver fibrosis/cirrhosis patients. Therefore, the prevention of HSC activation is an important strategy for treating severe liver injury. This study examined the effects of KR62776, a new peroxisome proliferator activated receptor gamma (PPARgamma) agonist, on the rate of cell proliferation and expression of alpha-smooth muscle actin (alpha-SMA) in rat hepatic stellate HSC-T6 cells. In addition, its effects on the liver damage induced by carbon tetrachloride were investigated. KR62776 caused the apoptosis of activated HSC-T6 cells with the concomitant decrease in the alpha-smooth muscle actin levels in a time- and concentration-dependent manner. However, KR62776 did not cause the apoptosis of human HepG2 and rat McARH7777 hepatoma cells, suggesting that KR62776 has a specific effect on stellate cells. KR62776 increased the levels of Gadd45, p27, p21 and PPARgamma proteins but decreased the cell cyclerelated proteins, such as cdk2, cyclin B and cyclin D1. These changes were reversed by BADGE, a specific PPARgamma antagonist, indicating that the effects of KR62776 are, at least in part, PPARgamma-dependent. In addition, KR62776 administration showed some protection against carbon tetrachloride-induced hepatocellular damage in rats. Overall, these results suggest that KR62776 may have potential in the chemoprevention of liver fibrosis/cirrhosis. PMID- 20361311 TI - In vivo evidence of the immunomodulatory activity of orally administered Aloe vera gel. AB - The gels of Aloe species contain immunomodulatory components such as aloctin A and acemannan. Most studies on these gels were performed in in vitro cell culture systems. Although several studies examined their immunomodulatory activity in vivo, the route of administration was intraperitoneal or intramuscular. Here, we evaluated the in vivo immunomodulatory activity of processed Aloe vera gel (PAG) in mice. Oral administration of PAG significantly reduced the growth of C. albicans in the spleen and kidney following intravenous injection of C. albicans in normal mice. PAG administration also reduced the growth of C. albicans in streptozotocin-induced diabetic mice. PAG administration did not increase ovalbumin (OVA)-specific cytotoxic T lymphocyte (CTL) generation in normal mice, but did increase it in high-fat-diet induced diabetic mice. These findings provide the first clear evidence for the immunomodulatory activity of orally administered Aloe vera gel. PMID- 20361312 TI - Inhibitory effect of cantharidin on osteoclast differentiation and bone resorption. AB - Regulation of receptor activator of nuclear factor kappaB-ligand (RANKL)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. We identified the inhibitory effects of cantharidin on RANKL-induced differentiation and bone resorptive activities of osteoclasts in macrophage-like RAW264.7 cells. Interestingly, cantharidin significantly inhibited RANKL-induced ERK/MAP kinase activation and protein phosphatase 2A (PP2A) activity. In addition, cantharidin significantly inhibited RANKL-induced mRNA expression of transcription factors and osteoclast-specific genes (especially Fra-2 and cathepsin K, respectively). Although further studies might be required to elucidate the precise mechanism of cantharidin's action on osteoclast differentiation and bone resorptive activities, our results suggested that cantharidin-mediated inactivation of PP2A could prevent RANKLinduced activation of ERK/MAP kinase and transcription factors such as AP-1 and NFATc1, with subsequent inhibition of osteoclast-specific gene expression required for efficient osteoclast differentiation and bone resorption. PMID- 20361313 TI - The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze. AB - Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum. PMID- 20361314 TI - Activation of CREB by St. John's wort may diminish deletorious effects of aging on spatial memory. AB - St. John's wort (Hypericum perforatum) is one of the leading psychotherapeutic phytomedicines. Beneficial effects of this herb in the treatment of mild to moderate depression are well known. In this study we tested a hypothesis that St. John's wort alleviates age-related memory impairments by increasing the levels of cyclic adenosine 3', 5'-monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) in hippocampus. Middleaged rats (18 month-old) displayed a decline in the acquisition of spatial working memory (p < 0.001) in the Morris water maze (MWM). Chronic administration of Hypericum perforatum (HP) (350 mg/kg for 21 days), potently and significantly improved the processing of spatial information in the aged rats (p < 0.001). Also the herb increased the levels of pCREB in the aged rat's hippocampus (p < 0.01) as measured by western immunoblotting. Aging caused significant locomotor impairments as tested in the open field (p < 0.001) but not in the MWM test. However, these were unaffected by treatment with HP. Thus, this study indicates that St. John's wort effectively prevents aging-induced deterioration of spatial memory in 18 month-old rats, possibly by the activation of CREB regulated genes associated with memory formation. It appears that mechanism is probably inactive in young rats. PMID- 20361315 TI - Phentolamine inhibits the pacemaker activity of mouse interstitial cells of Cajal by activating ATP-sensitive K+ channels. AB - The aim of this study was to clarify if phentolamine has proven effects on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine involving the ATPsensitive K(+) channels and adrenergic receptor. The actions of phentolamine on pacemaker activities were investigated using whole cell patch-clamp technique and intracellular Ca(2+) analysis at 30 degrees C in cultured mouse intestinal ICC. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. Treatment with phentolamine reduced the frequency and amplitude of the pacemaker currents and increased the resting outward currents. Moreover, under current clamping (I = 0), phentolamine hyperpolarized the ICC membrane and decreased the amplitude of the pacemaker potentials. We also observed that phentolamine inhibited spontaneous [Ca(2+)](i) oscillations in ICC. The alpha-adrenergic drugs prazosin, yohimbine, methoxamine, and clonidine had no effect on ICC intestinal pacemaker activity and did not block phentolamine induced effects. Phentolamine-induced effects on the pacemaker currents and the pacemaker potentials were significantly inhibited by ATP sensitive K(+) channel blocker glibenclamide, but not by TEA, apamin, or 4-aminopyridine. In addition, the NO synthase inhibitor, L-NAME and the guanylate cyclase inhibitor, ODQ were incapable of blocking the phentolamine-induced effects. These results demonstrate that phentolamine regulates the pacemaker activity of ICC via ATP-sensitive K(+) channel activation. Phentolamine could act through an adrenergic receptor- and also through NO-independent mechanism that involves intracellular Ca(2+) signaling. PMID- 20361318 TI - [Dermatologic Rehabilitation]. PMID- 20361316 TI - Capillary electrophoretic separation of poly(ethylene glycol)-modified granulocyte-colony stimulating factor. AB - We evaluated the utility of capillary electrophoretic methods for analyzing poly(ethylene glycol) (PEG)-modified granulocyte-colony stimulating factor (G CSF), a long-acting form of GCSF for the treatment of cancer therapy-induced neutropenia. Low- and high-molecularweight PEG-G-CSF conjugates prepared with aldehyde-activated PEG-5K and PEG-20K were separated by high-performance size exclusion chromatography (HP-SEC), capillary zone electrophoresis (CZE), and sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE). HPSEC showed low resolution for separating mono- and di-PEG-G-CSFs. SDS-CGE had higher resolution, but required a long analysis and had low peak efficiency. CZE could successfully separate both PEG-5K- and PEG-20K-conjugated G-CSFs with a running time of 20 min and high peak efficiency. In conclusion, CZE was better than SDS-CGE for separating PEG-G-CSF conjugates and will be useful for PEGylation studies, such as reaction monitoring for optimization of the PEGylation reaction, and purity and stability tests of PEG-G-CSF. PMID- 20361319 TI - [Change in color of a papillomatous nevus]. AB - A 43-year-old patient presented with a skin tumor on her back that had been slowly changing in color. Dermatoscopy showed an asymmetric lesion with two different parts. One part exhibited characteristics of a melanoma (blue-white veil, irregular pigment network) and the other an unspecific pattern of a papillomatous nevus. Histological examination of the completely excised tumor revealed a nevus-associated melanoma. PMID- 20361320 TI - [Management of pyoderma gangrenosum. An update on clinical features, diagnosis and therapy]. AB - Pyoderma gangrenosum is a rare neutrophilic inflammatory skin disease, mostly observed in middle-aged adults. Etiology and pathogenesis remain unclear. Autoimmune mechanisms including immune complex-mediated neutrophilic vascular reactions have been suggested. The hallmark finding in pyoderma gangrenosum is painful ulcers with sharply circumscribed and demarcated, frequently undermined, livid borders and a necrotic base. Pyoderma gangrenosum has been described in association with a great variety of systemic disorders, ranging from inflammatory bowel diseases to myeloproliferative disorders. The diagnosis of pyoderma gangrenosum is based primarily on the clinical presentation and course. It is usually a diagnosis of exclusion. Histopathological and laboratory findings in pyoderma gangrenosum are nonspecific. The aims of therapy are the complete suppression of inflammatory disease activity, promotion of wound healing and control of pain. Frequently, successful treatment of associated diseases leads to an improvement or complete remission of pyoderma gangrenosum. Surgical interventions, including aggressive ulcer excision, recipient site preparation and autologous skin grafting have to be avoided during the active phase of the disease because the likely occurrence of pathergy inducing new lesions at surgical sites and causing a worsening the original lesions. PMID- 20361321 TI - [The significance of chronic prostatitis for the etiopathology of prostate cancer]. AB - Although prostate cancer is of crucial impact as a common disease of men, numerous relationships remain unknown, particularly concerning its pathogenesis. A novel approach regarding the origin and development of prostate cancer is a phenomenon that has already been investigated in other human cancers: cancerogenesis due to chronic inflammation. Hence, the present review introduces the current state of research concerning the relationship between chronic prostatitis and prostate cancer. In addition to histological and biochemical features, the latest discoveries are discussed, including the relationship between the pathogenesis of prostate cancer and infection by the novel gammaretrovirus XMRV, similar to cervical cancer associated with HPV. PMID- 20361322 TI - Are great tits (Parus major) inhabiting the vicinity of a pulp mill healthy? Impacts on physiology and breeding performance. AB - The evaluation of pollution effects on wildlife provides biologically meaningful information concerning environmental quality and possible impacts on populations and can be used as an early warning of environmental change. We aimed to assess the potential effects of exposure to atmospheric pollution from pulp mill emissions on the morphology, physiology, and reproductive performance of the great tit (Parus major). Great tits from a population inhabiting the vicinity of a pulp mill had significantly higher feather mercury levels and were physiologically distinct from other birds not under the direct influence of the pollution source. This distinction, due to significantly higher levels of red blood cell-glutathione peroxidase antioxidant activity, in birds from the vicinity of the pulp mill, was observed both in autumn and winter and was repeatable between years. No detectable effects were observed on breeding performance or nestling morphology and physiology. The effects of pollution in this study seem to be related to increased levels of oxidative stress. PMID- 20361323 TI - Formation of soluble microbial products by activated sludge under anoxic conditions. AB - In this work, both experimental and modeling approaches are used to explore the formation of soluble microbial products (SMP) by activated sludge under anoxic conditions. With substrate consumption, the SMP concentration increases gradually. Utilization associated products (UAP) are the main fraction of SMP when substrate is present; whereas biomass associated products (BAP) are the major content of SMP as substrate is completely consumed. The fraction of the accumulated SMP accounts for 3-4% of initial organic substrate. Three dimensional excitation emission matrix analysis results indicate that the SMP concentration increases in the denitrification process. The accumulation of nitrite up to 22.6 mg/l under anoxic conditions has no significant effect on the SMP formation. With a consideration of SMP formation under anoxic conditions, an ASM3-based denitrification model is developed. The results show that the developed model is able to capture the relationship between the SMP formation and the substrate consumption by activated sludge in the denitrification process. PMID- 20361324 TI - Effects of pH and corn steep liquor variability on mannitol production by Lactobacillus intermedius NRRL B-3693. AB - Lactobacillus intermedius NRRL B-3693 produced mannitol, lactic acid, and acetic acid when grown on fructose at 37 degrees C. The optimal pH for mannitol production from fructose by the heterofermentative lactic acid bacterium (LAB) in pH-controlled fermentation was at pH 5.0. It produced 160.7 +/- 1.1 g mannitol in 40 h with a volumetric productivity of 4.0 g l(-1) h(-1) in a simplified medium containing 250 g fructose, 50 g corn steep liquor (CSL), and 33 mg MnSO(4) per liter. However, the mannitol production by the LAB was severely affected by the variability of CSL. The supplementation of CSL with soy peptone (5 g/l), tryptophan (50 mg/l), tryptophan (50 mg/l) plus tyrosine (50 mg/l), or commercial protease preparation (2 ml/100 g of CSL) enhanced the performance of the inferior CSL and thus helped to overcome the nutrient limitations. PMID- 20361325 TI - Enhanced production of 2,3-butanediol from glycerol by forced pH fluctuations. AB - The glycerol fermentation by Klebsiella pneumoniae occurs by receiving more than five liquid products-organic acids, diols, and ethanol. Aiming to direct the glycerol conversion towards predominant production of 2,3-butanediol (2,3-BD), the main influencing parameters (the aeration and the pH) were investigated during fed-batch processes. The regime of intensive aeration (2.2 vvm air supply) was evaluated as most favorable for 2,3-BD synthesis and ensured the decrease of all other metabolites. Thus, without pH control, 52.5 g/l 2,3-BD were produced, as the carbon conversion of glycerol into 2,3-BD reached 60.6%. Additional enhancement in 2,3-BD production (by significant increase of glycerol utilization) was achieved by the development of a new method of "forced pH fluctuations". It was realized by consecutive raisings of pH using definite DeltapH value, at exact time intervals, allowing multiple variations. Thus, the optimal conditions for maximal glycerol consumption were defined, and 70 g/l 2,3 BD were produced, which is the highest amount obtained from glycerol as a sole carbon source until now. The forced pH fluctuations emphasized pH as a governing factor in microbial conversion processes. PMID- 20361327 TI - Catalase overexpression reduces the germination time and increases the pathogenicity of the fungus Metarhizium anisopliae. AB - Catalases and peroxidases are the most important enzymes that degrade hydrogen peroxide into water and oxygen. These enzymes and superoxide dismutase are the first lines of cell defense against reactive oxygen species. Metarhizium anisopliae displays an increase in catalase-peroxidase activity during germination and growth. To determine the importance of catalase during the invasion process of M. anisopliae, we isolated the cat1 gene. cat1 cDNA expression in Escherichia coli and the subsequent purification of the protein confirmed that the cat1 gene codes for a monofunctional catalase. Expression analysis of this gene by RT-PCR from RNA isolated from fungus grown in liquid cultures showed a decrease in the expression level of the cat1 gene during germination and an increase during mycelium growth. The expression of this gene in the fungus during the infection process of the larvae of Plutella xylostella also showed a significant increase during invasive growth. Transgenic strains overexpressing the cat1 gene had twice the catalase activity of the wild-type strain. This increase in catalase activity was accompanied by a higher level of resistance to exogenous hydrogen peroxide and a reduction in the germination time. This improvement was also observed during the infection of P. xylostella larvae. M. anisopliae transgenic strains overexpressing the cat1 gene grew and spread faster in the soft tissue of the insect, reducing the time to death of the insect by 25% and the dose required to kill 50% of the population 14-fold. PMID- 20361326 TI - Unraveling polyketide synthesis in members of the genus Aspergillus. AB - Aspergillus species have the ability to produce a wide range of secondary metabolites including polyketides that are generated by multi-domain polyketide synthases (PKSs). Recent biochemical studies using dissected single or multiple domains from PKSs have provided deep insight into how these PKSs control the structural outcome. Moreover, the recent genome sequencing of several species has greatly facilitated the understanding of the biosynthetic pathways for these secondary metabolites. In this review, we will highlight the current knowledge regarding polyketide biosynthesis in Aspergillus based on the domain architecture of non-reducing, highly reducing, and partially reducing PKSs, and PKS-non ribosomal peptide synthetases. PMID- 20361328 TI - Water access, water scarcity, and climate change. AB - This article investigates the approaches of the various discourses operating in the water sector and how they address the issues of scarcity and equitable access under projected climate change impacts. Little synergy exists between the different approaches dealing with these issues. Whilst being a sustainable development and water resources management issue, a holistic view of access, scarcity and the projected impacts of climate change is not prevalent in these discourses. The climate change discourse too does not adequately bridge the gap between these issues. The projected impacts of climate change are likely to exacerbate the problems of scarcity and equitable access unless appropriate adaptation strategies are adopted and resilience is built. The successful delivery of accessible water services under projected climate change impacts therefore lies with an extension of the adaptive water management approach to include equitable access as a key driver. PMID- 20361329 TI - An adult onset Still's disease mimicking pneumonia. AB - Adult onset Still's disease is a rare systemic inflammatory disease of unknown origin. It is common to involve liver and spleen, and less often lungs. A 24-year old man presenting with spiking fever, pulmonary infiltrations, and pleural effusion on the right side mimicking pneumonia. All serologic tests of infectious causes, antinuclear antibody, and rheumatoid factor were negative. He was diagnosed as Adult onset Still's disease according to the criteria of Yamaguchi. Adult onset Still's disease is considering in the differential diagnosis pneumonia that is unresponsive to antimicrobial treatment, negative cultures and serologically diagnostic laboratory tests, and high-level serum ferritin. PMID- 20361330 TI - Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus. AB - Regulatory T cells (Tregs) are supposed to stop immune responses in the course of immune activation. However, chronic activation of immune system in systemic lupus erythematosus (SLE) and many other autoreactive disorders are evidence of malfunction of this system. Therefore, it is plausible to quantify presence of these cells in different diseases. Forty-one patients with diagnosis of SLE were enrolled in this study. Patients were divided into two groups of patients with active and inactive disease based on the disease activity score. Flow cytometry analysis was used to determine the frequency of regulatory T cells in peripheral blood according to high expression of CD25 and intracellular Forkhead/winged helix (Foxp3). Further 30 healthy individuals considered as control group. Significantly less CD4+CD25hi regulatory T cells were detected in active patients (P < 0.001) compared to healthy individuals. The percentage of CD4+CD25hi cells were inversely correlated with the SLEDAI disease score in patients with active disease (r = -0.837, P < 0.0001). Patients with active disease had lower frequencies of CD4+Foxp3+ cells. However, increased frequencies of CD4+Foxp3+ T cells were observed in peripheral blood of patients with inactive disease compared with active patients or healthy individuals (P < 0.010). Moreover, a significant difference between the proportion of CD4+CD25-Foxp3+ population in healthy controls and patients with active disease was shown (P < 0.0005). Presence of lower frequencies of Tregs in patients with SLE could be evaluated as an immune turbulence and could be employed as a target for immunotherapeutic manipulation. However, controversies need to be resolved. PMID- 20361331 TI - The earliest evidence of true lambdoid craniosynostosis: the case of "Benjamina", a Homo heidelbergensis child. AB - BACKGROUND: The authors report the morphological and neuroimaging findings of an immature human fossil (Cranium 14) diagnosed with left lambdoid synostosis. DISCUSSION: The skull was recovered at the Sima de los Huesos site in Atapuerca (Burgos, Spain). Since the human fossil remains from this site have been dated to a minimum age of 530,000 years, this skull represents the earliest evidence of craniosynostosis occurring in a hominid. A brief historical review of craniosynostosis and cranial deformation is provided. PMID- 20361332 TI - Quality of life in childhood hydrocephalus: a review. AB - PURPOSE: Those with hydrocephalus view quality of life (QOL) as the most important of outcomes. The literature on QOL in hydrocephalus is growing, and we now recognize several of the factors that potentially influence outcome in these children. Neurosurgeons should be aware of the latest findings and how to critically analyze the QOL literature. METHODS: This paper will attempt to review some general scientific concepts about QOL that neurosurgeons can apply to all patients. As well, we will describe, in some detail, what we currently understand about QOL issues in childhood hydrocephalus specifically, and where future research might take us. CONCLUSIONS: Quality-of-life assessment is becoming important in advancing our scientific understanding of hydrocephalus. PMID- 20361333 TI - Astaxanthin addition improves human neutrophils function: in vitro study. AB - PURPOSE: The aim of the present study was to evaluate the in vitro effect of carotenoid astaxanthin (ASTA) on the phagocytic and microbicidal capacities, cytokine release, and reactive oxygen species production in human neutrophils. METHODS: The following parameters were evaluated: cytotoxic effect of ASTA on human neutrophils viability, phagocytic and microbicidal capacities of neutrophils by using Candida albicans assay, intracellular calcium mobilization (Fura 2-AM fluorescent probe), superoxide anion (lucigenin and DHE probes), hydrogen peroxide (H2O2, phenol red), and nitric oxide (NO.) (Griess reagent) production, activities of antioxidant enzymes (total/Mn-SOD, CAT, GPx, and GR), oxidative damages in biomolecules (TBARS assay and carbonyl groups), and cytokine (IL-6 and TNF-alpha) release. RESULTS: Astaxanthin significantly improves neutrophil phagocytic and microbicidal capacity, and increases the intracellular calcium concentration and NO. production. Both functional parameters were accompanied by a decrease in superoxide anion and hydrogen peroxide and IL-6 and TNF-alpha production. Oxidative damages in lipids and proteins were significantly decreased after ASTA-treatment. CONCLUSIONS: Taken together our results are supportive to a beneficial effect of astaxanthin-treatment on human neutrophils function as demonstrated by increased phagocytic and fungicide capacity as well as by the reduced superoxide anion and hydrogen peroxide production, however, without affecting neutrophils capacity to kill C. albicans. This process appears to be mediated by calcium released from intracellular storages as well as nitric oxide production. PMID- 20361334 TI - Analysis of free and protein-bound ceramides by tape stripping of stratum corneum from dogs. AB - The free and protein-bound ceramides of dog stratum corneum (SC) were analyzed by thin-layer chromatography after tape stripping of the abdomen of five dogs. The sphingoid bases were identified by gas-liquid chromatography as sphingosine, phytosphingosine, and 6-hydroxysphingosine. Electrospray ionization-ion trap mass spectrometry was used to characterize the protein-bound ceramides containing sphingosine and omega-hydroxy long-chain fatty acids. Although the molecular species were the same ones in all dogs, wide quantitative variations in the patterns of SC ceramides were observed in different breeds of dogs. The free ceramide concentration changed with the depth of SC, with a higher concentration in the deep layers, whereas the concentration of protein-bound ceramides remained constant. These results show that canine SC is close to that of humans with respect to ceramides. PMID- 20361335 TI - Improving prediction of lateral node spread in low rectal cancers--multivariate analysis of clinicopathological factors in 1,046 cases. AB - INTRODUCTION: This study aims to search for independent predictors of lateral node metastasis in low rectal cancers. MATERIALS AND METHODS: We analyzed 1,046 patients who underwent curative resection for lower rectal cancer in our prospectively collected database. All lymph nodes were dissected from the fresh specimen, and their locations were documented prospectively according to the classification by the Japanese Society of Cancer of the Colon and Rectum. RESULTS: More than 35% of the patients had demonstrated upward nodal metastasis in the direction of the inferior mesenteric vessels, while 11% demonstrated lateral node metastasis, which was present in 17.3% of patients with T3 and T4 lesions. Multivariate analysis revealed five factors to be statistically significant independent predictors of lateral node metastasis: female sex, tumors that were not well differentiated, pathological T3 and above, positive microscopic lymphatic invasion, and positive mesorectal nodes. Using the variables sex, differentiation, T stage, and mesorectal nodes as risk factors, because these could be elucidated preoperatively, the presence of lateral node metastasis was then analyzed according to the number of positive risk factors. When there were fewer than three positive factors, the risk of lateral nodal spread was low (4.5%). When three or more risk factors were positive, the odds of lateral node metastasis were more than 7.5 times higher (p < 0.001). CONCLUSION: The findings of this study provide a scoring system that can be used to guide the clinician to the presence of lateral node metastasis in low rectal cancers. PMID- 20361336 TI - The SUMO conjugation pathway in Populus: genomic analysis, tissue-specific and inducible SUMOylation and in vitro de-SUMOylation. AB - Covalent attachment of the small ubiquitin-like modifier (SUMO) to proteins in eukaryotic cells can regulate an assortment of cellular processes including transcription, and DNA-protein and protein-protein interactions. We identified gene models and found evidence for expression of genes involved in SUMOylation and SUMO deconjugation in Populus. We detected SUMOylated proteins in diverse organ and tissue types. SUMOylation was altered during responses to heat shock, desiccation, peroxide and irrigation of roots with high salt solution. SUMO deconjugation from substrates was sensitive to cysteine protease inhibitors. Product sizes and sensitivity to inhibitors are consistent with poly-SUMO chain formation as an intermediate step in SUMO redistribution to substrates in plant cells responding to treatments. The SUMOylation pathway is active in Populus and substrate conjugation to SUMO is a rapid response to multiple inducers. PMID- 20361337 TI - Constitutive expression of CaSRP1, a hot pepper small rubber particle protein homolog, resulted in fast growth and improved drought tolerance in transgenic Arabidopsis plants. AB - Transient and long-term shortages of fresh water are major adverse environmental factors that cause dramatic reductions in crop production and distribution globally. In this study, we isolated a full-length CaSRP1 (Capsicum annuum stress related protein 1) cDNA, which was rapidly induced by dehydration in hot pepper plants. The predicted CaSRP1 protein sequence exhibited significant amino acid identity to putative stress-related proteins and the small rubber particle protein (SRPP) found in rubber trees (Hevea brasiliensis). To study the cellular functions of CaSRP1, transgenic Arabidopsis plants (35S:CaSRP1) that constitutively expressed the CaSRP1 gene were constructed. Overexpression of CaSRP1 resulted in enhanced root and shoot growth and earlier bolting in the transgenic plants relative to wild-type plants. In addition, 35S:CaSRP1 overexpressors exhibited enhanced tolerance to drought stress as compared to the control plants. These results suggest that CaSRP1 plays dual functions as a positive factor for tissue growth and development and for drought-defensive responses. A possible cellular function of SRPP homologs in non-rubber-producing plants in relation to drought stress tolerance is discussed. PMID- 20361338 TI - Comparative sequence analyses indicate that Coffea (Asterids) and Vitis (Rosids) derive from the same paleo-hexaploid ancestral genome. AB - The complete sequence of Vitis vinifera revealed that the rosid clade derives from a hexaploid ancestor. At present, no analysis of complete genome sequence is available for an asterid, the other large eudicot clade, which includes the economically important species potato, tomato and coffee. To elucidate the genomic history of asterids, we compared the sequence of an 800 kb region of diploid Coffea genome to the orthologous regions of V. vinifera, Populus trichocarpa and Arabidopsis thaliana. We found a very high level of collinearity between around 80 genes of the three rosid species and Coffea. Collinearity comparisons between orthologous and paralogous regions indicates that (1) the Coffea (and consequently all asterids) and rosids share the same hexaploid ancestor; (2) the diploidization process (loss of duplicated and redundant copies from the whole genome duplication) was very advanced in the most recent common ancestor of rosids and asterids. Finally, no additional polyploidization events were detected in the Coffea lineage. Differences in gene loss rates were detected among the three rosid species and linked to the divergence in protein sequences. PMID- 20361339 TI - A probabilistic finite element analysis of the stresses in the augmented vertebral body after vertebroplasty. AB - Fractured vertebral bodies are often stabilized by vertebroplasty. Several parameters, including fracture type, cement filling shape, cement volume, elastic moduli of cement, cancellous bone and fractured region, may all affect the stresses in the augmented vertebral body and in bone cement. The aim of this study was to determine numerically the effects of these input parameters on the stresses caused. In a probabilistic finite element study, an osteoligamentous model of the lumbar spine was employed. Seven input parameters were simultaneously and randomly varied within appropriate limits for >110 combinations thereof. The maximum von Mises stresses in cancellous and cortical bone of the treated vertebral body L3 and in bone cement were calculated. The loading cases standing, flexion, extension, lateral bending, axial rotation and walking were simulated. In a subsequent sensitivity analysis, the coefficients of correlation and determination of the input parameters on the von Mises stresses were calculated. The loading case has a strong influence on the maximum von Mises stress. In cancellous bone, the median value of the maximum von Mises stresses for the different input parameter combinations varied between 1.5 (standing) and 4.5 MPa (flexion). The ranges of the stresses are large for all loading cases studied. Depending on the loading case, up to 69% of the maximum stress variation could be explained by the seven input parameters. The fracture shape and the elastic modulus of the fractured region have the highest influence. In cortical bone, the median values of the maximum von Mises stresses varied between 31.1 (standing) and 61.8 MPa (flexion). The seven input parameters could explain up to 80% of the stress variation here. It is the fracture shape, which has always the highest influence on the stress variation. In bone cement, the median value of the maximum von Mises stresses varied between 3.8 (standing) and 12.7 MPa (flexion). Up to 75% of the maximum stress variation in cement could be explained by the seven input parameters. Fracture shape, and the elastic moduli of bone cement and of the fracture region are those input parameters with the highest influence on the stress variation. In the model with no fracture, the maximum von Mises stresses are generally low. The present probabilistic and sensitivity study clearly showed that in vertebroplasty the maximum stresses in the augmented vertebral body and in bone cement depend mainly on the loading case and fracture shape. Elastic moduli of cement, fracture region and cancellous bone as well as cement volume have sometimes a moderate effect while number and symmetry of cement plugs have virtually no effect on the maximum stresses. PMID- 20361340 TI - Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis. AB - Low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Furthermore, several recent studies have shown that gene polymorphisms are related to osteoporosis. However, no study has yet linked polymorphisms in the vitamin D receptor (VDR) gene and bone mass in AIS. Accordingly, the authors examined the association between bone mass and VDR gene polymorphisms in 198 girls diagnosed with AIS. The VDR BsmI (rs1544410), FokI (rs2228670) and Cdx2 (rs11568820) polymorphisms and bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed and compared to their levels in healthy controls. Mean LSBMD and FNBMD in AIS patients were lower than in age- and sex-matched healthy controls (P = 0.0022 and P = 0.0013, respectively). A comparison of genotype frequencies in AIS patients and controls revealed a significant difference for the BsmI polymorphism only (P = 0.0054). Furthermore, a significant association was found between the VDR BsmI polymorphism and LSBMD. In particular, LSBMD in AIS patients with the AA genotype was found to be significantly lower than in patients with the GA (P < 0.05) or GG (P < 0.01) genotypes. However, no significant association was found between LSBMD or FNBMD and the VDR FokI or Cdx2 polymorphisms. These results suggest that the VDR BsmI polymorphism is associated with LSBMD in girls with AIS. PMID- 20361341 TI - Effect of multilevel lumbar disc arthroplasty on spine kinematics and facet joint loads in flexion and extension: a finite element analysis. AB - Total disc arthroplasty (TDA) has been successfully used for monosegmental treatment in the last few years. However, multi-level TDA led to controversial clinical results. We hypothesise that: (1) the more artificial discs are implanted, the stronger the increases in spinal mobility and facet joint forces in flexion and extension; (2) deviations from the optimal implant position lead to strong instabilities. A three-dimensional finite element model of the intact L1-L5 human lumbar spine was created. Additionally, models of the L1-L5 region implanted with multiple Charite discs ranging from two to four levels were created. The models took into account the possible misalignments in the antero posterior direction of the artificial discs. All these models were exposed to an axial compression preload of 500 N and pure moments of 7.5 Nm in flexion and extension. For central implant positions and the loading case extension, a motion increase of 51% for two implants up to 91% for four implants and a facet force increase of 24% for two implants up to 38% for four implants compared to the intact spine were calculated. In flexion, a motion decrease of 5% for two implants up to 8% for four implants was predicted. Posteriorly placed implants led to a better representation of the intact spine motion. However, lift-off phenomena between the core and the implant endplates were observed in some extension simulations in which the artificial discs were anteriorly or posteriorly implanted. The more artificial discs are implanted, the stronger the motion increase in flexion and extension was predicted with respect to the intact condition. Deviations from the optimal implant position lead to unfavourable kinematics, to high facet joint forces and even to lift-off phenomena. Therefore, multilevel TDA should, if at all, only be performed in appropriate patients with good muscular conditions and by surgeons who can ensure optimal implant positions. PMID- 20361342 TI - Prevalence of Internet use amongst an elective spinal surgery outpatient population. AB - Nationally 62% of individuals in Ireland have internet access. Previous published work has suggested that internet use is higher among those with low back pain. We aimed to determine the levels of internet access and use amongst an elective spinal outpatient population and determine what characteristics influence these. We distributed a self-designed questionnaire to patients attending elective spinal outpatient clinics. Data including demographics, history of surgery, number of visits, level of satisfaction with previous consultations, access to the internet, possession of health insurance, and details regarding use of the internet to research one's spinal complaint were collected. 213 patients completed the questionnaire. 159 (75%) had access to the internet. Of this group 48 (23%) used the internet to research their spinal condition. Increasing age, higher education level, and possession of health insurance were all significantly associated with access to the internet (p < 0.05). A higher education level predicted greater internet use while possession of insurance weakly predicted non use (p < 0.05). In our practice, internet access is consistent with national statistics and use is comparable to previous reports. Approximately, one quarter of outpatients will use the internet to research their spinal condition. Should we use this medium to disseminate information we need to be aware some groups may not have access. PMID- 20361343 TI - Low-temperature T4-like coliphages vB_EcoM-VR5, vB_EcoM-VR7 and vB_EcoM-VR20. AB - Bacteriophages vB_EcoM-VR5, vB_EcoM-VR7 and vB_EcoM-VR20, showing an unusual low temperature plating profile and producing constantly growing plaques, were isolated from aquatic environments of Lithuania. Although vB_EcoM-VR5, vB_EcoM VR7 and vB_EcoM-VR20 resembled phage T4 both in their genome size and in their major structural protein (gp23) pattern, physiological properties of all three phages tested differed significantly from those of T4. With an optimum temperature for plating around 24 degrees C and a high efficiency of plating in the range 7-30 degrees C, bacteriophages vB_EcoM-VR7 and vB_EcoM-VR20 failed to plate at 37 degrees C, whereas phage vB_EcoM-VR5 could not be plated at 40 degrees C. Sequence analysis of diagnostic g23 PCR products revealed that g23 of vB_EcoM-VR5, vB_EcoM-VR7 and vB_EcoM-VR20 differed from the corresponding T4 g23 DNA sequence by 21, 21 and 20%, respectively. PMID- 20361344 TI - Molecular modeling of 4-methylphthalonitrile for dye sensitized solar cells using quantum chemical calculations. AB - The geometries, electronic structures, polarizabilities, and hyperpolarizabilities of organic dye sensitizer 4-methylphthalonitrile was studied based on Hartree-Fock (HF) and density functional theory (DFT) using the hybrid functional B3LYP. Ultraviolet-visible (UV-Vis) spectrum was investigated by time dependent-density functional theory (TD-DFT). Features of the electronic absorption spectrum in the visible and near-UV regions were assigned based on TD DFT calculations. The absorption bands are assigned to pi->pi* transitions. Calculated results suggest that three lowest energy excited states of 4 methylphthalonitrile are due to photo induced electron transfer processes. The interfacial electron transfer between semiconductor TiO2 electrode and dye sensitizer 4-methylphthalonitrile is due to an electron injection process from excited dye to the semiconductor's conduction band. The role of cyanine and methyl group in 4-methylphthalonitrile in geometries, electronic structures, and spectral properties were analyzed. PMID- 20361345 TI - Urocanic acid as an efficient hydroxyl radical scavenger: a quantum theoretical study. AB - The photoisomerization of urocanic acid (UCA)--which is present in human skin epidermis, where it acts as a sunscreen--from its trans isomer to its cis isomer upon exposure to UV-B radiation is known to cause immunosuppression. In recent years, the antioxidant properties of UCA (it acts as a hydroxyl radical scavenger) have also been recognized. In view of this, the mechanisms of stepwise reactions of trans-UCA with up to four hydroxyl radicals were investigated. The molecular geometries of the different species and complexes involved in the reactions (reactant, intermediate and product complexes, as well as transition states) were optimized via density functional theory in the gas phase. Solvation in aqueous media was treated with single point energy calculations using DFT and the polarizable continuum model. Single point energy calculations in the gas phase and aqueous media were also carried out using second-order Moller-Plesset perturbation theory (MP2). The AUG-cc-pVDZ basis set was employed in all calculations. Corrections for basis set superposition error (BSSE) were applied. Vibrational frequency analysis was performed for each optimized structure to ensure the validity of the optimized transition states. It was found that the binding of the first OH. radical to UCA involves a positive energy barrier, while subsequent reactions of OH. radicals are exergonic. Transition states were successfully located, even in those cases where the barrier energies were found to be negative. The cis-trans isomerization barrier energy of UCA and that of the first OH. radical addition to UCA are comparable, meaning that both processes can occur simultaneously. It was found that UCA could serve as an antioxidant in the form of an efficient OH. radical scavenger. PMID- 20361346 TI - Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies. AB - We describe a procedure for performing quantitative analyses of fields f(r) on molecular surfaces, including statistical quantities and locating and evaluating their local extrema. Our approach avoids the need for explicit mathematical representation of the surface and can be implemented easily in existing graphical software, as it is based on the very popular representation of a surface as collection of polygons. We discuss applications involving the volumes, surface areas and molecular surface electrostatic potentials, and local ionization energies of a group of 11 molecules. PMID- 20361347 TI - Shear strength of the bond to primary dentin: influence of Er:YAG laser irradiation distance. AB - The aim of this study was to assess in vitro the influence of Er:YAG laser irradiation distance on the shear strength of the bond between an adhesive restorative system and primary dentin. A total of 60 crowns of primary molars were embedded in acrylic resin and mechanically ground to expose a flat dentin surface and were randomly assigned to six groups (n = 10). The control group was etched with 37% phosphoric acid. The remaining five groups were irradiated (80 mJ, 2 Hz) at different irradiation distances (11, 12, 16, 17 and 20 mm), followed by acid etching. An adhesive agent (Single Bond) was applied to the bonding sites, and resin cylinders (Filtek Z250) were prepared. The shear bond strength tests were performed in a universal testing machine (0.5 mm/min). Data were submitted to statistical analysis using one-way ANOVA and the Kruskal-Wallis test (p<0.05). The mean shear bond strengths were: 7.32 +/- 3.83, 5.07 +/- 2.62, 6.49 +/- 1.64, 7.71 +/- 0.66, 7.33 +/- 0.02, and 9.65 +/- 2.41 MPa in the control group and the groups irradiated at 11, 12, 16, 17, and 20 mm, respectively. The differences between the bond strengths in groups II and IV and between the bond strengths in groups II and VI were statistically significant (p<0.05). Increasing the laser irradiation distance resulted in increasing shear strength of the bond to primary dentin. PMID- 20361348 TI - Prenatal ontogeny of subspecific variation in the craniofacial morphology of the Japanese macaque (Macaca fuscata). AB - We cross-sectionally investigated prenatal ontogeny of craniofacial shape in the two subspecies of the Japanese macaque (Macaca fuscata fuscata and Macaca fuscata yakui) using a geometric morphometric technique to explore the process of morphogenetic divergence leading to the adult morphological difference between the subspecies. The sample comprised a total of 32 formalin-fixed fetal specimens of the two subspecies, in approximately the second and third trimesters. Each fetal cranium was scanned using computed tomography to generate a three dimensional surface model, and 68 landmarks were digitized on the external and internal surface of each cranium to trace the growth-related changes in craniofacial shape of the two subspecies. The results of our study demonstrated that the two subspecies generally shared the same craniofacial growth pattern. Both crania tend to exhibit relative contraction of the neurocranium in the mediolateral and superoinferior directions, a more superiorly positioned cranial base, a more vertically oriented occipital squama, and a more anteriorly positioned viscerocranium as the cranial size increased. However, distinctive subspecific differences, for example relatively narrower orbital breadth, higher orbit, higher position of the nuchal crest, and more protrudent snout found in Macaca fuscata yakui were already present during the prenatal period. This study demonstrated that morphological differentiation in the craniofacial shape may occur at a very early stage of the fetal period even between closely related subspecies of the Japanese macaque. PMID- 20361349 TI - IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. AB - Interleukin-6 (IL-6) is a growth and survival factor in human glioblastoma cells and plays an important role in malignant progression. However, its role in glioblastoma invasion is still unknown. This study shows how IL-6 promotes cell invasion and migration in U251 and T98G glioblastoma cell lines. The underlying mechanism includes both protease-dependent and -independent manners. Stimulation with IL-6 increased MMP9 expression in the two cell lines but had no influence on MMP2 expression. Fascin-1 is a cell skeleton binding protein and plays a key role in cell migration and invasion. Its binding style directly influences cell morphology and tendency to become deformed. After IL-6 exposure, fascin-1 expression increased in an IL-6 dose-dependent manner. Immunofluorescence also revealed that the binding style of fascin-1 had changed after IL-6 exposure, resulting in a more invasive phenotype of the cells. Three most commonly emphasized invasion-associated signaling pathways, including JAK-STAT3, p42/44 MAPK, and PI3K/AKT, were verified to further illustrate its underlying mechanism. Only phosphorylation of STAT3 at ser 727 site paralleled the IL-6 stimulation, and JSI-124, a specific JAK-STAT3 pathway blocker, deterred the invasion and migration promotive effect of IL-6, indicating that the JAK/STAT3 pathway mediates signal transduction. Furthermore, IL-6 also acts in a paracrine fashion to promote vascular endothelial cell migration, thus facilitating tumor angiogenesis and invasion. These results suggest that IL-6 promotes glioblastoma cell invasion and angiogenesis and may be a potential anti-invasion target. PMID- 20361350 TI - Cadmium stress: an oxidative challenge. AB - At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions. PMID- 20361351 TI - Angiotensin (1-7) and its receptor Mas are expressed in the human testis: implications for male infertility. AB - The presence of classical components of the renin-angiotensin system has been demonstrated in the male reproductive tract, mainly in the testes and epididymis. The objective of this study was to verify the localization of angiotensin (Ang) (1-7) and its receptor Mas in human testis. The study included 12 men with previously proven fertility submitted to orchiectomy for prostate cancer and 20 infertile men submitted to testicular biopsy for infertility work-up, comprising a subgroup with obstructive azoospermia/normal spermatogenesis (n = 8) and another with non-obstructive azoospermia and severely impaired spermatogenesis (n = 12). Testicular tissue samples were processed by immunohistochemistry and real time polymerase chain reaction. Ang-(1-7) was strongly expressed in the interstitial compartment, mainly in Leydig cells, with similar intensity in all groups evaluated. The peptide was also detected in the seminiferous tubules, but with much less intensity compared to interstitial cells. The receptor Mas was equally distributed between interstitial and tubular compartments and was found in all layers of the normal seminiferous epithelium. However, neither Ang-(1-7) nor Mas were detected in the seminiferous tubules of samples with impaired spermatogenesis. The testicular samples of infertile men with impaired spermatogenesis (non-obstructive azoospermia) expressed Mas and ACE2 mRNA at lower concentrations (fold change = 0.06 and 0.04, respectively, P < 0.05) than samples with full spermatogenesis (obstructive azoospermia). This shows, for the first time, the immunolocalization of Ang-(1-7) and its receptor Mas in testes of fertile and infertile men, and suggests that this system may be altered when spermatogenesis is severely impaired. PMID- 20361352 TI - Role of dietary iodine and cruciferous vegetables in thyroid cancer: a countrywide case-control study in New Caledonia. AB - Exceptionally high incidence rates of thyroid cancer have been reported in New Caledonia, particularly in Melanesian women. To clarify the reasons of this elevated incidence, we conducted a countrywide population-based case-control study in the multiethnic population of Caledonian women. The study included 293 cases of thyroid cancer and 354 population controls. Based on a food frequency questionnaire, we investigated the role in thyroid cancer of food items rich in iodine-such as seafood-and of vegetables containing goitrogens-such as cruciferous vegetables. A measure of total daily iodine intake based on a food composition table was also used. Our findings provided little support for an association between thyroid cancer and consumption of fish and seafood. We found that high consumption of cruciferous vegetables was associated with thyroid cancer among women with low iodine intake (OR = 1.86; 95% CI: 1.01-3.43 for iodine intake <96 microg/day). The high consumption of cruciferous vegetables among Melanesian women, a group with mild iodine deficiency, may contribute to explain the exceptionally high incidence of thyroid cancer in this group. PMID- 20361353 TI - Meeting the cervical cancer screening needs of underserved women: the National Breast and Cervical Cancer Early Detection Program, 2004-2006. AB - OBJECTIVE: To examine the extent to which the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), has helped to meet the cervical cancer screening needs of underserved women. METHODS: Low-income, uninsured women 18-64 years of age are eligible for free cervical cancer screening services through NBCCEDP. We used data from the US Census Bureau to estimate the number of eligible women, based on insurance status and income. The estimates were adjusted for hysterectomy status using the National Health Interview Survey and the Behavioral Risk Factor Surveillance System. We used administrative data from NBCCEDP to obtain the number of women receiving NBCCEDP-funded Papanicolaou (Pap) tests. We then calculated the percentage of NBCCEDP-eligible women who received free cervical cancer screening through NBCCEDP. We also used the NHIS to calculate the percentage of NBCCEDP-eligible women screened nationally and the percentage unscreened. RESULTS: In 2004-2006, nearly 9% (775,312 of 8.9 million) of NBCCEDP eligible women, received NBCCEDP-funded Pap test. Rates varied substantially by age groups, race, and ethnicity. NBCCEDP-eligible women 40-64 years of age had a higher screening rate (22.6%) than eligible women 18-39 years of age (2.3%). Non Hispanic women had a higher screening rate (9.3%) than Hispanic women (7.3%). Among non-Hispanics, the screening rate was highest among American Indian and Alaska Native (AIAN) women (36.1%) and lowest among women of different race combinations (4.6%), The percentage of eligible women screened in each state ranged from 2.0 to 38.4%. CONCLUSIONS: Although NBCCEDP provided cervical cancer screening services to 775,312 low-income, uninsured women, this number represented a small percentage of those eligible. In 2005, more than 34% of NBCCEDP-eligible women (3.1 million women) did not receive recommended Pap tests from either NBCCEDP or other sources. PMID- 20361354 TI - Chronic administration of cyclosporine A changes expression of BDNF and TrkB in rat hippocampus and midbrain. AB - Neurotrophins, including the brain-derived neurotrophic factor (BDNF), are essential for regulating neuronal differentiation in developing brains. BDNF and its receptor tyrosine kinase receptor B (TrkB) are involved in neuronal signaling, survival and plasticity. Cyclosporine A (CsA) is a potent immunosuppressive agent which prevents allograft rejection in organ transplantation and various immunological diseases. We investigated whether chronic administration of CsA decreases BDNF gene expression in rats, and the influence of CsA on mRNA levels of TrkB receptors was also examined. For 30 days of CsA (10 mg/kg/day) administration, the expression of BDNF and TrkB mRNA was significantly decreased in the hippocampus and midbrain, but there was no significant difference in the cortex. CsA (0, 1, 5 10, 15 ug/ml) down-regulated BDNF and TrkB gene expression through cultured SH-SY5Y cells, as did all-trans retinoic acid (ATRA), and there was no effect on cell viability. These experimental results indicate that suppression of the BDNF and TrkB mRNA, protein level of BDNF expression in the hippocampus and midbrain may be related to altered behavior observed following chronic administration of CsA. A common mechanism of adverse effects of CsA induced depressive symptoms may involve neurotoxicity mediated by down-regulation of brain BDNF and TrkB. PMID- 20361355 TI - 'The human prerogative': a critical analysis of evidence-based and other paradigms of care in substance abuse treatment. AB - Present-day substance abuse treatment is characterized by a compelling demand for applying evidence-based interventions. Vehement discussions between policymakers, practitioners and researchers illustrate this clash of differing paradigms. The aim of this article is to situate evidence-based practice among the leading paradigms of care and to elucidate its implicit assumptions and potential implications. Evidence-based practice is inherent in the empirical-analytical paradigm of care and science, founded upon randomized and controlled studies. This paradigm is compared with the phenomenological-existential and the critical post-structural paradigm, which focus on elaborating the human potential and exploring individuals' subjective interpretations, and on criticizing social inequalities and striving for compliance with human rights, respectively. Evidence-based practice and the methodological rigidity in each paradigm are analyzed critically. We conclude that through the dialectical integration of these diverse approaches, evidence, existence/humanism and social emancipation can be combined for the benefit of the human prerogative of care. PMID- 20361356 TI - Bone tissue, lyophilized and stored at room temperature for 15 days or more, is not capable of transmitting HIV, HCV or HBV. AB - Over the past 57 years, 17 recipients of frozen bone have been infected with: HIV (Centers for Disease Control and Prevention in Morb Mortal Wkly Rep MMWR 37(39):597-599, 1988; Li et al. in J Formos Med Assoc 100(5):350-351, 2001; Simonds et al. in NEJM 326(11):726-732, 1992; Schratt et al. in Unfallchirurg 99(9):679-684, 1996); HCV (Eggen and Nordbo in NEJM 326(6):411, 1992; Conrad et al. in J Bone Joint Surg Am 77:214-224, 1995; Trotter in J Bone Joint Surg Am 851(11):2215-2217, 2003; Tugwell et al. in Ann of Internal Med 143(9):648-654, 2005); or HBV (Shutkin in J Bone Joint Surg Am 36:160-162, 1954). However, bone, lyophilized and stored at room temperature, has never transmitted these viral diseases. A literature review was undertaken to determine whether there is any evidence that lyophilized bone is capable of transmitting HIV, HCV and HBV. PMID- 20361357 TI - Learning about urban congregations and HIV/AIDS: community-based foundations for developing congregational health interventions. AB - Religious congregations are important community institutions that could help fight HIV/AIDS; however, barriers exist, particularly in the area of prevention. Formative, participatory research is needed to understand the capacity of congregations to address HIV/AIDS. This article describes a study that used community-based participatory research (CBPR) approaches to learn about congregation-sponsored HIV activities. CBPR strategies were used throughout the study, including proposal development, community expert interviews, Community Advisory Board, congregational telephone survey, congregational case studies, and congregational feedback sessions. Involving community consultants, experts, and advisory board members in all stages of the study helped the researchers to conceptualize congregational involvement in HIV, be more sensitive to potential congregational concerns about the research, achieve high response rates, and interpret and disseminate findings. Providing preliminary case findings to congregational participants in an interactive feedback session improved data quality and relationships with the community. Methods to engage community stakeholders can lay the foundation for future collaborative interventions. PMID- 20361358 TI - Quantitative assessment of visceral fat in morbidly obese patients by means of wide-bore MRI and its relation to lower esophageal sphincter pressure and signs of gastroesophageal reflux. AB - BACKGROUND: The aim of this study was to quantitatively assess visceral adipose tissue (VAT) by means of a wide-bore MR scanner in a cohort of morbidly obese patients referred for bariatric surgery. Furthermore, it was investigated whether gastroesophageal reflux disease (GERD) and lower esophageal sphincter pressure (LESP) are related to the volume of visceral fat masses. METHODS: Twenty-five morbidly obese patients (nine male, 16 female) were prospectively enrolled. In addition to common anthropometric measures of obesity, VAT was determined quantitatively by multi-slice MRI. Symptoms of GERD were evaluated using a standardized questionnaire, while endoscopy of the upper gastrointestinal tract was performed to reveal pathologies of the gastroesophageal junction. LESP was evaluated by esophageal manometry. RESULTS: Study population showed a body mass index (BMI) between 35.2 and 59.1 kg/m(2). Waist-to-hip ratio and VAT were significantly higher (p < 0.0001; p = 0.0021) in males (1.05 +/- 0.05; 8.89 +/- 2.33 l) than in females (0.86 +/- 0.07; 6.04 +/- 1.28 l). VAT was not correlated to BMI. LESP values and GERD-related symptoms were neither dependent on anthropometric measures nor on VAT in our cohort. CONCLUSIONS: VAT did not show a positive correlation with BMI in our cohort of extremely obese subjects, indicating a pronounced fat deposition in subcutaneous tissue compartment. Moreover, this indicates that VAT is limited to a gender-dependent maximum volume for each individual and seems to be no further increasing in extremely obese subjects. This might be the reason that neither symptoms nor endoscopic findings of GERD nor LESP were significantly influenced by the stage of morbid obesity. PMID- 20361359 TI - Chemotherapy use and risk of bone marrow suppression in a large population-based cohort of older women with breast and ovarian cancer. AB - We studied 65,521 women with breast cancer and 7,420 women with ovarian cancer aged >= 65 identified from the 16 areas of the Surveillance, Epidemiology and End Results program linked with Medicare data during 1991-2002. Bone marrow toxicity associated with chemotherapy was defined using diagnosis codes from Medicare inpatient, outpatient and physician claims. The time to event Cox regression was utilized to estimate the risk of bone marrow toxicity. Use of anthracyclines, taxanes or platinums was associated with increased risks of short- (<=3 months) and long-term (>3 months) anemia and neutropenia in patients with breast cancer. Alkylating agents or antimetabolites were additional significant predictors of anemia in women with ovarian cancer. Patients who received chemotherapy (irrespective of regimens) were twice (breast cancer) or three times (ovarian cancer) as likely to develop thrombocytopenia compared to those not receiving chemotherapy. Among women with breast cancer, patients receiving cyclophosphamide, methotrexate and fluorouracil regimens (hazard ratio=19.0, 95% CI=11.2-32.5), platinum/taxane therapy (21.9, 11.9-40.4) or the cyclophosphamide, adriamycin and fluorouracil regimen (32.5, 19.6-53.9) were strongly associated with risk of aplastic anemia. There was a dose-response relationship between the use of taxane or platinum and the risk of bone marrow suppression, whereas the increased risk of bone marrow toxicity was consistently higher in those with use of alkylating agents or anthracycline-based regimens irrespective of the increasing number of cycles received. In conclusion, there was an association between chemotherapy use and clinical manifestations of bone marrow toxicities in a population-based setting. PMID- 20361360 TI - Dose-dense and dose-intense chemotherapy for small cell ovarian cancer: 2 cases and review of literature. AB - Small cell carcinomas of the ovary (SCCO) are rare and aggressive malignant neoplasms carrying a poor prognosis. Although multi-modality treatment including chemotherapy leads to a high initial response rate, the majority of these patients relapse quickly and die within 2 years of diagnosis. Because these tumours are rare, there is no consensus to support any particular approach to management. We present 2 cases and review the relevant literature to make a number of recommendations. The treatment of these unusual cases should to be individually discussed in a multi-disciplinary team and multi-modality treatment including surgery, chemotherapy and radiotherapy should be considered for patients with limited disease. Conservative, fertility-preserving surgery may be considered in younger women with early-stage disease. Induction chemotherapy with weekly dose-dense and dose-intense carboplatin and taxane is useful. Prophylactic cranial irradiation (PCI) may be considered in patients in remission after primary treatment with chemotherapy or surgery. PMID- 20361361 TI - The role of Pygopus 2 in rat glioma cell growth. AB - Glioma is a common malignant tumor of the human neural system, and Wnt signaling activation is closely connected with glioma malignancy. Pygopus 2 (Pygo2) was recently discovered as a component of the Wnt signaling pathway regulating beta catenin/Tcf dependent transcription. However, the role of Pygo2 in glioma cells has not yet been defined. In the current study, we investigated the role of Pygo2 in rat glioma C6 cells for the first time. Our results showed that over expression of Pygo2 promoted cell proliferation as well as enhanced cell cycle progression from G1 to S phase associated with an increase in the expression of the Wnt target gene cyclin D1. In contrast, knockdown of Pygo2 suppressed cell proliferation with cell cycle block from G1 to S phase and down-regulation of cyclin D1. In addition, the expression of Pygo2 and cyclin D1 in 67 glioma tissue samples was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunochemistry. The data indicated that tumor grade was significantly associated with over-expression of Pygo2 and cyclin D1. We conclude that Pygo2 is highly expressed in and promotes the growth of glioma cells by an increase in the expression of cyclin D1 to improve G1/S transition. PMID- 20361362 TI - Electrocardiographic predictors of adverse cardiovascular events in suspected poisoning. AB - Poisoning is the second leading cause of injury-related fatality in the USA and the leading cause of cardiac arrest in victims under 40 years of age. The study objective was to define the electrocardiographic (ECG) predictors of adverse cardiovascular events (ACVE) complicating suspected acute poisoning (SAP). This was a case-control study in adults at three tertiary-care hospitals and one regional Poison Control Center. We compared 34 cases of SAP complicated by ACVE to 101 consecutive control patients with uncomplicated SAP. The initial ECG was analyzed for rhythm, intervals, QT dispersion, ischemia, and infarction. ECGs were interpreted by a cardiologist, blinded to study hypothesis and case data. Subjects were 48% male, with mean age 42 +/- 19 years. In addition to clinical suspicion of poisoning in 100% of patients, routine toxicology screens were positive in 77%, most commonly for benzodiazepines, opioids, and/or acetaminophen. Neither the ventricular rate, the QRS duration, nor the presence of infarction predicted the risk of ACVE. However, the rhythm, QTc, QT dispersion, and presence of ischemia correlated with the risk of ACVE. Independent predictors of ACVE based on multivariable logistic regression were prolonged QTc, any non-sinus rhythm, ventricular ectopy, and ischemia. Recursive partitioning analysis identified very low risk criteria (94.1% sensitivity, 96.2% NPV) and high risk criteria (95% specificity). Among patients with SAP, the presence of QTc prolongation, QT dispersion, ventricular ectopy, any non-sinus rhythm, and evidence of ischemia on the initial ECG are strongly associated with ACVE. PMID- 20361363 TI - The nature of hyperthermia in neuroleptic malignant syndrome and the use of bromocriptine. PMID- 20361364 TI - Unilateral blindness following acute methanol poisoning. PMID- 20361366 TI - [Clinical research in partnership: musculoskeletal surgery]. AB - As a result of the demographic development of industrial nations the number of musculoskeletal diseases and injuries rises continuously. This challenges health care as well as clinical research and demands additional endeavours. The United Nations have recognised this issue at an early stage. With their in 2000 declared Bone and Joint Decade they have significantly contributed to a sustainable support of research activities. The German government has also perceived the need and, with their roadmap programme, encourages research of musculoskeletal disease.Today, surgical and orthopaedic clinics increasingly support the exchange between research and clinic and run their own research departments. The Berlin Center for Musculoskeletal Surgery (CMSC) and its research institute Julius Wolff Institut show the potential for surgical research. It shows that based on a clinical understanding of the problem, basic research needs to be complemented in a network with partners from other disciplines. However, interdisciplinary cooperation demands new and individual ways of communication and education. The example in Berlin also illustrates that the research on prevention not only completes the network but more over opens unexpected possibilities in understanding basic research and translation. PMID- 20361367 TI - [Research in surgery]. PMID- 20361365 TI - [Replacement of infected knee and hip endoprostheses]. AB - Infections occur in 0.5-5% of cases after implantation of an endoprosthesis and represent one of the most severe complications of artificial joint replacements. Approximately 300,000 primary implantations for hip and knee prostheses are carried out in Germany annually with a corresponding number of early and late infections. This means that approximately 4,000-6,000 cases are to be expected annually. Periprosthetic infections normally lead to a significant loss of function and quality of life for patients and the complex remediation is costly. Therefore, preventive measures, such as perioperative prophylaxis with antibiotics, maintaining highly sterile conditions during operations and an expedient selection of patients are of substantial importance. The basic principles of an adequate restoration include identification of the pathogen, local eradication of the infection mostly after removal of the prosthesis, pathogen-oriented systemic and local antibiotic therapy and finally re implantation of the revision prosthesis under infection-free conditions. The standard procedure for revision surgery is a two-phase replacement with maintenance of an infection-free interval before renewal of the prosthesis. The use of single-phase or multi-phase strategies, as well as the selection of cemented or cement-free revision, varies between centers as a definitive evaluation is not yet available.The most important parameters for successful treatment of periprosthetic infections have been identified as the earliest possible diagnosis, radical surgical cleansing with an adequate antibiotic therapy and successful restoration has been reported in approximately 80% of cases. Because of the complex therapy regime, treatment in specialized centers is generally recommended especially under the aspect of a demanding patient monitoring. PMID- 20361368 TI - [German general and visceral surgery: positioning within the international scientific community]. AB - BACKGROUND: Assessment of scientific performance is critical for selection committees and research funding. The present work evaluated the standing of German surgical research within the international community. METHODS: A database analysis was performed in December 2009 using the ISI Web of Science. RESULTS: The highest impact factor of surgical journals is currently 8.460 with a median impact of all journals of 1.369. Leading academic surgeons have an h-index of more than 60. German surgeons are within the top five leading researchers in the fields of surgery for esophageal and pancreatic cancer, thyroid, hernia, and liver/kidney transplantation. Among the 50 institutions with most publications on a particular topic, 4-5 German centers are mostly represented. The top positions are in total decisively occupied by leading universities in the USA. CONCLUSION: On the basis of scientific parameters German surgical research can compete with leading international centers in certain fields, but should aim to increase the overall impact of research by publishing more in journals with above average impact factors. PMID- 20361369 TI - [Recruiting multicenter surgical studies in Germany]. PMID- 20361370 TI - [Indications and principles of metabolic surgery]. AB - Bariatric surgery is known to be the most effective and long lasting treatment for morbid obesity and many related conditions, but now mounting evidence suggests it may be among the most effective forms of treatment for metabolic diseases and conditions including type 2 diabetes, hypertension, high cholesterol levels, non-alcoholic fatty liver disease and obstructive sleep apnea. Surgery for severe obesity goes way beyond weight loss. This surgery results in the complete remission or significant improvement of type 2 diabetes and other life threatening diseases in most patients. The new name metabolic surgery was created and reflects this expanded and evolving view of surgery. Therefore, metabolic surgery is expected to play an ever increasing role in managing these diseases. New research results indicate that metabolic surgery may improve insulin resistance and secretion by mechanisms independent of weight loss, most likely involving changes in gastrointestinal hormones. Many patients with type 2 diabetes experience complete remission within days of metabolic surgery, long before significant weight is lost. This has led to a new concept that metabolic surgery may also be appropriate for diabetic individuals who are of normal weight or only slightly overweight. PMID- 20361372 TI - Science & gender: vision and mission. PMID- 20361373 TI - Discrepancies in national incidence trends for hip fracture: why does Austria have such a high incidence? PMID- 20361375 TI - Intra-abdominal migration of a Kirschner wire. PMID- 20361374 TI - Hypoxic hepatitis - epidemiology, pathophysiology and clinical management. AB - Hypoxic hepatitis (HH), also known as ischemic hepatitis or shock liver, is characterized by centrilobular liver cell necrosis and sharply increasing serum aminotransferase levels in a clinical setting of cardiac, circulatory or respiratory failure. Nowadays it is recognized as the most frequent cause of acute liver injury with a reported prevalence of up to 10% in the intensive care unit. Patients with HH and vasopressor therapy have a significantly increased mortality risk in the medical intensive care unit population. The main underlying conditions contributing to HH are low cardiac output and septic shock, although a multifactorial etiology is found in the majority of patients. HH causes several complications such as spontaneous hypoglycemia, respiratory insufficiency due to the hepatopulmonary syndrome, and hyperammonemia. HH reverses after successful treatment of the basic HH-causing disease. No specific therapies improving the hepatic function in patients with HH are currently established. Early recognition of HH and its underlying diseases and subsequent initiation of therapy is of central prognostic importance. The purpose of this review is to provide an update on the epidemiology, pathophysiology, and diagnostic and therapeutic options of HH. PMID- 20361376 TI - Gender aspects in medical publication - the Wiener klinische Wochenschrift. AB - OBJECTIVE: Medicine is a discipline where there are still pronounced gender imbalances. Whereas worldwide about 50% of beginners in medical schools are female, only few of them reach leading positions. Our aim was to analyze how this situation is reflected in a peer-reviewed general medical-scientific journal. METHODS: We screened all papers submitted to the Wiener klinische Wochenschrift - The Middle European Journal of Medicine between January 2001 and September 2009, analyzing the percentage of female first authors of submitted papers and accepted papers, the contribution of female authors depending on the type of article and medical specialty, and the percentage of invited female peer reviewers as well as the quality of their reviews. MAJOR RESULTS: During the period studied, a total of 2507 manuscripts were submitted to Wiener klinische Wochenschrift. 26% of these papers had female first authors, and this proportion increased continuously from 16% in 2001 to 32% in 2007, whereafter it remained constant. The proportion of papers submitted by female first authors was dependent on the medical subspecialty (e.g. 48% female first authors of pediatric papers, 12% female first authors of cardiology papers). There was no difference in the acceptance rate of papers by male and female first authors; however, a somewhat higher rate of papers with female first authors was subject to rapid rejection (21% vs. 16%). Papers with female first authors more often named a different corresponding author than papers with male first authors, and in most of these cases the corresponding author was a man. More than 40% of all submitted original papers, 24% of the review articles, but only 10% of the editorials had female first authors. During the years studied only 5-11% of reviewers were women, despite that the quality of their reviews was generally better than those by men. Among the 21 members of the editorial board only one is a woman. CONCLUSION: Between 2001 and 2007 the percentage of manuscripts submitted to Wiener klinische Wochenschrift by female authors constantly increased and is now around 30%, reaching almost 50% in some specialties such as pediatrics. Nevertheless, there remains a massive gender imbalance in Wiener klinische Wochenschrift: review papers or invited editorials are only rarely authored by female researchers, a very low percentage of peer reviewers is female - although the quality of their reviews is generally better - and only one member of the editorial board is female. Even though this is mostly a reflection of the general situation in academic medicine, medical journals can and must take action and contribute to the elimination of these gender inequalities. PMID- 20361377 TI - Clinical experience with routine use of a single combined mapping and ablation catheter for isolation of pulmonary veins in patients with paroxysmal atrial fibrillation. AB - BACKGROUND: Catheter-based isolation of pulmonary veins has become established treatment for patients with paroxysmal atrial fibrillation. We wished to simplify the interventional procedure by using a single novel multipolar catheter for mapping and ablation in appropriate patients. METHODS: Sixty-four patients with paroxysmal atrial fibrillation scheduled for pulmonary vein isolation were screened by cardiac computed tomography for anatomic suitability to undergo a simplified procedure with the high-density mesh ablator catheter (MESH) as the only left atrial device. The procedure was undertaken in 38 patients matching the criteria of four clearly separated pulmonary veins with ostial diameters 15-25 mm; the remaining 26 patients served as a control group and were treated using a three-dimensional mapping system guided ablation using a circular mapping catheter and a single-point ablation catheter. RESULTS: In all 38 patients, all four pulmonary veins could be accessed and mapped with the MESH. Using the MESH, electrical isolation was achieved in 142/148 (96%) pulmonary veins with recorded potentials. In the control group, 100/105 (95%) pulmonary veins with recorded potentials could be isolated. After 6 months, clinical results did not differ significantly between the two treatment groups. CONCLUSION: In appropriate patients, the routine single catheter approach with the MESH for mapping and ablation yields a high acute success rate despite the reduced complexity of the procedure. Long-term data on clinical success rates are needed to justify this simplified approach. PMID- 20361378 TI - Evolution of cardiovascular risk factors among 18-year-old males in Austria between 1986 and 2005. AB - OBJECTIVE: The aims of the study were to determine time trends in cardiovascular risk factors among young Austrian males between 1986 and 2005 and to examine socioeconomic and geographic differences. METHODS: Data on Austrian conscripts were derived from the nationwide compulsory medical investigations held at military induction at 18 years of age. Four cohorts (1986-1990: n = 252,799; 1991 1995: n = 209,266; 1996-2000: n = 208,427; 2001-2005: n = 209,168) were examined with respect to their place of residence and level of education. Height, weight, waist circumference, blood pressure, serum total-cholesterol and triglycerides were measured. Mean body mass index (BMI) was calculated: overweight was defined as BMI between 25 and <30 and obesity as BMI >or= 30. The Chi-squared test and ANOVA were used to test group differences. RESULTS: During the 20-year observation period the prevalence of overweight increased from 13.3% to 15.7% (p < 0.001) and that of obesity from 2.6% to 5.4% (p < 0.001); in accordance, mean BMI and waist circumference increased significantly. Blood pressure and serum total-cholesterol level decreased (p < 0.001) during the period studied, although triglyceride levels (p < 0.001) increased. A significant east-west gradient was identified for the prevalence of overweight and obesity, waist circumference and mean BMI, with lower values in the urban population compared with those of rural inhabitants. Mean BMI and the prevalence of overweight and obesity were higher in conscripts belonging to lower socioeconomic strata. CONCLUSION: Our study demonstrates a clear increase of mean BMI, waist circumference and the prevalence of overweight and obesity in Austrian male adolescents during the past 20 years. Conscripts from rural regions and with lower levels of education showed the highest values. The investigation of conscript health appears to be a useful tool for risk surveillance in the male population. PMID- 20361379 TI - Lipoprotein(a) predicts progression of carotid artery intima-media thickening in patients with type 2 diabetes: A four-year follow-up. AB - BACKGROUND: The aim of the study was to establish whether increased levels of serum lipoprotein(a) significantly contribute to an increase in intima-media thickness and the number of carotid artery plaques, and consequently to cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: Lipoprotein(a) levels, intima-media thickness and the number of carotid artery plaques were determined at the beginning of the study in 146 patients with type 2 diabetes. Patients were divided into two groups according to serum lipoprotein(a) levels (> or 30 mg/dl had more cardiovascular events, the difference was not statistically significant. CONCLUSIONS: These results indicate that lipoprotein(a) is an independent, genetically determined risk factor closely associated with progression of intima media thickness in type 2 diabetes. PMID- 20361380 TI - [Referral success to psychotherapy of patients with personality disorders - therapeutic consequences]. AB - BACKGROUND: Psychotherapy plays an important role in the treatment of patients suffering from a personality disorder. It is known that many patients with personality disorders do not take up psychotherapy or drop out of treatment prematurely. The aim of the present study was the detection of factors in patients with personality disorders which influence the referral to psychotherapy. METHODS: Personality characteristics (socio-demographic parameters, affect experience and regulation, quality of object relations, character traits, level of interpersonal problems) of 297 patients of a psychoanalytic-psychotherapeutic outpatient clinic were assessed. Their influence on therapy engagement were analysed by means of logistic regressions. RESULTS: Within univariate analysis certain personality traits (mature psychological functioning vs. negativistic personality features) showed predictive power. The multivariate analysis identified the patients' educational level as the principal indicator for psychotherapy utilization. CONCLUSIONS: Consequences for diagnostic initial interviews in connection with the role of the educational level for the therapeutic alliance are discussed. Further, the impact of economic aspects on therapy engagement is discussed. PMID- 20361381 TI - Efficacy and safety of a new pediatric artesunate-mefloquine drug formulation for the treatment of uncomplicated falciparum malaria in Gabon. AB - Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria. The aim of this clinical trial was to evaluate the efficacy, safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate mefloquine and a new co-blister tablet formulation. A total of 71 children aged 1 13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight: 10-20 kg, pediatric group (n = 41); 20-40 kg, tablet group (n = 30). All the children were treated once daily for three days: the pediatric group received the novel granule formulation, the tablet group received the co-blister tablets. The PCR-corrected cure rate on day 28 was evaluated. There was no reappearance of parasitemia during the follow-up period and the day 28 cure rate was therefore 100% in per-protocol analysis. In intention-to-treat analysis the cure rates were 95% in the pediatric group and 97% in the tablet group. The most frequent adverse events were vomiting (17%), abdominal pain (11%) and headache (17%). This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children. PMID- 20361382 TI - Sclerosing mesenteritis, a rare cause of a retroperitoneal tumor. AB - Sclerosing mesenteritis is a chronic and extremely rare inflammatory process that predominantly affects the small bowel mesentery. However, the peripancreatic region, the omentum and the retroperitoneum can also be involved. The etiology and pathogenesis of the disease are as yet unknown, but autoimmune disorders, previous abdominal surgery, trauma, ischemia and drugs could play a role. The clinical picture is nonspecific and varies from asymptomatic to diffuse abdominal complaints. Radiologic work-up and histologic evaluation of a biopsy specimen usually do not reveal typical findings and therefore establishment of the correct diagnosis is challenging. Owing to the rarity of the disease, there is no consensus on optimal pharmaceutical treatment and most patients are treated empirically. Surgical therapy is limited to biopsies for histologic confirmation of the tumor and management of complications. We report a case of a 51-year-old man with a large retroperitoneal mass. Magnetic resonance angiography showed a 9.7 x 7.7 x 5.9 cm tumor above the aortic bifurcation with encasement of the aorta and the vena cava. CT-guided biopsy was inconclusive but surgical biopsy provided a histologic diagnosis of sclerosing mesenteritis. The operative and postoperative course was uneventful and therapy with prednisolone and azathioprine was started. At 6 months' follow-up, the patient was in good condition and asymptomatic. Sclerosing mesenteritis, though a rare entity, should be included in the differential diagnosis when a patient presents with a mesenterial or retroperitoneal tumor. PMID- 20361386 TI - Helping Haiti: Texas physicians help earthquake victims. PMID- 20361383 TI - Different pattern of regional metabolic abnormalities in Takotsubo cardiomyopathy as evidenced by F-18 FDG PET-CT. PMID- 20361387 TI - Texas needs physicians trained in public health: a new 4-year integrated MD/MPH degree program. AB - Traditionally, medicine and public health have not worked as synergistic disciplines because they are based on fundamentally different models. However, a number of very recent imperatives emphasize the need for dual training in these fields to address major public health problems facing society as well as the documented and forecasted workforce shortages. In response to this need, two University of Texas institutions based in San Antonio, Texas, partnered in 2007 to offer a dual 4-year Doctor of Medicine/Master of Public health (MD/MPH) degree program, one of a handful in the nation. Approximately 65 students (or 10% of three consecutive medical school classes) are currently enrolled. The dual-degree program meets the requirements of both degree programs while giving shared MPH credit for relevant courses taken in the medical curriculum and medical school credit for some courses in the public health curriculum. However, 75% of the MPH coursework originates at the School of Public Health. Initial results from focus groups conducted after the first year showed a high degree of student satisfaction, with frequent comments that the program was broadening their perspective on medicine and influencing their career and life goals. A dual MD/MPH degree is an important option for all medical students as a means of addressing pressing health issues in our society through combined training in medicine and the broader areas of prevention and population health. The four-year MD/MPH program, while posing challenges for faculty and students, attracts community- and prevention-minded medical students, reduces training costs (housing/living costs and lost time and wages before entering residency), and allows students to progress with the rest of their class. PMID- 20361388 TI - Pay cut: budget problems force Medicaid physician fee reduction. PMID- 20361389 TI - RECs to the rescue: regional centers help physicians use HIT. PMID- 20361390 TI - [The German Version of the Childhood Trauma Questionnaire (CTQ):Preliminary Psychometric Properties.] PMID- 20361391 TI - The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the Finnish Diabetes Prevention Study. AB - Physical activity exerts anti-inflammatory effects, but genetic variation may modify its influence. In particular, the rs1800629 single-nucleotide polymorphism (SNP) in the tumor necrosis factor ( TNF) gene and the rs1800795 SNP in the interleukin-6 ( IL6) gene have been found to modify the effect of exercise training on circulating levels of C-reactive protein (CRP) and IL-6, respectively. We assessed whether rs1800629 and rs1800795 modified the effect of moderate-to-vigorous physical activity on changes in serum levels of high sensitivity CRP and IL-6 in the Finnish Diabetes Prevention Study (DPS). Genotype and 1-year data on changes in physical activity, serum CRP and IL-6 were available for 390 overweight subjects with impaired glucose tolerance. The rs1800629 SNP in TNF interacted with the 1-year change in moderate-to-vigorous physical activity on changes in CRP among those who had high (>=3 mg/L) baseline CRP levels ( P = 0.034 for interaction). Carriers of the GG genotype showed a greater decrease in CRP with increasing physical activity than the individuals with the A allele. No interaction between the rs1800795 SNP in IL6 and changes in moderate-to-vigorous physical activity on the 1-year change in serum IL-6 was found. In conclusion, the rs1800629 SNP in the TNF gene may modify the effect of moderate-to-vigorous physical activity on serum levels of CRP. PMID- 20361392 TI - Long term predictors of post-partum glucose metabolism in women with gestational diabetes mellitus. AB - AIMS: The question asked by this study was whether beta-cell function expressed by insulin secretion/sensitivity measured during pregnancy in women with gestational diabetes (GDM) predicts post-partum long-term derangement in glucose metabolism. METHODS: Seventy-four Caucasian women with previous GDM were retested through a 75 g-2-h-OGTT after 8 [6] years (median[interquartile range]) from index pregnancy, measuring at pregnancy and follow-up insulin sensitivity, insulin secretion (1-h-incremental-insulin-area/incremental-glucose-area: DeltaAUC60 (I)/DeltaAUC60 (G)) as well as the product of Stumvoll-first-phase - secretion x insulin sensitivity (insulin-secretion-sensitivity index (ISSI). RESULTS: At follow-up 47 women were normotelerant to glucose and 27 had altered glucose metabolism (AGM:10 with type 2 diabetes and 17 with IGT). Women progressed to AGM had at their index pregnancy higher mean 2-h-OGTT-glucose area (1.15+/-0.09 VS. 1.09+/-0.09 mol l 2-h (-1);p=0.014), and lower DeltaAUC60 (I)/DeltaAUC60 (median [interquantile range]) (54.4 [51.7] vs. 73.4 [60] pmol mmol (-1)) and ISSI (2 977 [766] vs. 3 708 [1 141]; p<0.05 for both), but similar insulin sensitivity index 2.9 [2.5] VS. 3.2 [2.2] ml min (-1) m (-2);p=NS). Two-h OGTT-glucose area, or decrease in DeltaAUC60 (I)/DeltaAUC60 (G) and ISSI were significantly associated with glucose tolerance impairment and with raised adjusted risk for AGM while insulin sensitivity at pregnancy did no predict AGM development. CONCLUSIONS: In this group of women increased post-load plasma glucose and impaired beta-cell function assessed during GDM pregnancy predict long-term post-partum AGM, while insulin sensitivity measured at the same time does not. PMID- 20361393 TI - Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 levels in severely obese patients: what is the effect of weight loss? AB - INTRODUCTION: There is increased evidence that circulating levels of matrix metalloproteinases and their tissue inhibitors are altered in obesity and may be implicated in its pathogenesis. This study aimed to compare the serum concentrations of pro-matrix metalloproteinase-1 (pro-MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in severely obese patients with or without metabolic syndrome, and to investigate the potential effect of weight loss on their circulating levels. METHODS: A total of 102 severely obese subjects were included in our study. Of these, 61 had no other features of metabolic syndrome, while the rest were 41 age- and sex-matched subjects with severe obesity and metabolic syndrome according to the NCEP-ATP criteria. Fourty-two age and sex matched healthy lean individuals were used as controls. RESULTS: Severely obese subjects had higher circulating levels of TIMP-1 than the lean ones (120.6 +/- 50.6 vs. 89.0 +/- 35.2 ng/ml) and obese patients with metabolic syndrome had higher TIMP-1 levels than their metabolically healthy counterparts (134.8 +/- 38.4 vs. 111.0 +/- 55.62 ng/ml). A positive association was also found between TIMP-1 levels and various anthropometric and metabolic parameters in the obese subjects. Moreover, weight loss of more than 5% resulted in a significant reduction of the TIMP-1 levels in obese subjects, irrespective of the presence or not of metabolic syndrome. No significant differences in pro-MMP-1 concentrations were found between the obese (2.8 +/- 2.4 ng/ml) and lean individuals (2.8 +/- 0.8 ng/ml). CONCLUSIONS: In conclusion, we demonstrated that increased TIMP-1 serum levels are found in severely obese patients and particularly in these with metabolic syndrome, while weight loss of more than 5% resulted in reduction of TIMP-1 levels. PMID- 20361394 TI - Inpatient and outpatient health care utilization of children and adolescents with type 1 diabetes before and after introduction of DRGs. AB - OBJECTIVE: To analyze the frequency and length of hospital stays as well as the frequency of diabetes-associated outpatient visits of children and adolescents with type 1 diabetes before and after the introduction of DRGs (diagnosis-related groups) in German hospitals. METHODS: For this prospective cohort study, data from 2000 (before introduction of DRGs) to 2008 (after introduction) was extracted from the German diabetes documentation software DPV. Incidence rates of hospitalizations, length of hospital stays as well as the incidence rates of outpatient visits of 21,502 children and adolescents were estimated. The associations between the target parameters and DRG introduction, age, sex, diabetes duration, calendar year and migration background were estimated using generalized linear mixed models. RESULTS: Incidence of hospitalization was 0.45 (95% CI 0.44-0.45) per person-year (PY), mean number of hospital days 2.77/PY (95% CI: 2.76-2.79). Children had 5.3 (95% CI: 5.3-5.3) outpatient visits per PY on average. The number of hospital stays, inpatient days, and outpatient visits decreased significantly between 2000 and 2008. Time of introduction of DRGs was related to a significant rise in the number of hospital stays and outpatient visits (p<0.05). There was no significant relation to the number of hospital days. Compared with children younger than eleven years of age, 11- to 14-year-old children had significantly more, adolescents older than 14 years significantly less hospital stays (RR 1.2, 95% CI: 1.14-1.23 and 0.92, 95%, CI: 0.87-0.97, respectively). Migration background was significantly associated with worse results for all analyzed target variables (RR 1.21 for hospital stays, 1.26 for hospital days, 1.07 number of outpatient visits). CONCLUSIONS: The introduction of DRGs in the care of patients with pediatric diabetes mellitus resulted in a leveling of the reduction of the number of outpatient visits and hospital stays. Especially adolescents at the age of puberty and patients from families with migration background seem to require particular attention in health care. PMID- 20361395 TI - [African horse sickness and equine encephalosis: must Switzerland get prepared]. AB - African horse sickness (AHS) of equines is partly transmitted by the same culicoides species as Bluetongue (BT) disease in even-toed ungulates. Horses normally get seriously sick, with a high case fatality rate. Equine Encephalosis is another, but less-known viral disease of equines, caused by viruses of the same genus as BT and AHS. Like BT of serotype 8 in 2006, both diseases could theoretically be introduced to Europe anytime and spread rapidly then. After the lessons learnt from the most recent bluetongue outbreaks in Europe, the regulations and AHS-contingency plans in force must be updated. All stakeholders must be aware of the risks and take own measures to prevent a possible emergence of the diseases, and be prepared in case of an outbreak. PMID- 20361396 TI - Bacterial infections in horses: a retrospective study at the University Equine Clinic of Bern. AB - Bacterial infections present a major challenge in equine medicine. Therapy should be based on bacteriological diagnosis to successfully minimize the increasing number of infections caused by multidrug-resistant bacteria. The present study is a retrospective analysis of bacteriological results from purulent infections in horses admitted at the University Equine Clinic of Bern from 2004 to 2008. From 378 samples analyzed, 557 isolates were identified, of which Staphylococcus aureus, Streptococcus equi subsp. zooepidemicus and coliforms were the most common. Special attention was paid to infections with methicillin-resistant S. aureus (MRSA) ST398 and a non-MRSA, multidrug-resistant S. aureus clone ST1 (BERN100). Screening of newly-admitted horses showed that 2.2 % were carriers of MRSA. Consequent hygiene measures taken at the Clinic helped to overcome a MRSA outbreak and decrease the number of MRSA infections. PMID- 20361397 TI - [Rupture of the extensor carpi radialis tendon in two horses]. AB - Symptoms, diagnosis, therapy and clinical outcome of 2 horses which acquired a complete rupture of the extensor carpi radialis tendon by accident are described. The resulting gait abnormalities are very typical, so that the problem can be diagnosed already by clinical examination. With the help of ultrasound the diagnosis could be confirmed and the degree of damage quantified. The open wounds in the carpal region were surgically treated in a standing position and the limbs of both horses were kept under a splint bandage for 6 to 8 weeks. Prognosis in these cases was good, as both horses returned within 6 months back to their previous work. PMID- 20361401 TI - [Confidential medical research]. PMID- 20361402 TI - [Night and Sunday duty for Animal Welfare Association development--changes in regulations as of March 1 2010]]. PMID- 20361398 TI - [Swiss warmblood horse with symptoms of hereditary equine regional dermal asthenia without mutation in the cyclophylin B gene (PPIB)]. AB - Hereditary equine dermal asthenia (HERDA) is an autosomal recessive skin disease that affects predominantly Quarter Horses and related breeds. Typical symptoms are easy bruising and hyperextensible skin on the back. The prognosis is guarded, as affected horses cannot be ridden normally and are often euthanised. In the Quarter Horse, HERDA is associated with a mutation in cyclophilin B (PPIB), an enzyme involved in triple helix formation of collagen. Here we describe the case of a Swiss Warmblood filly with symptoms of HERDA without PPIB-mutation and in which we also could exclude Ehlers-Danlos syndrome Type IV, VI, VIIA, VIIB and VIIC (dermatosparaxis type) as etiological diseases. PMID- 20361404 TI - [At which point is one prepared for the second year operation and is one happy about one's choice]. PMID- 20361403 TI - [Spring meeting of the Swiss Union of Veterinary diagnostics SVVLD]. PMID- 20361405 TI - [Family members in the intensive care unit: effects and mastering the situation. A review of qualitative studies]. AB - Having a family member in the intensive care unit is a very stressful and demanding situation for the whole family. The aim of this study is to explore how family members are affected by critical illness and how they deal with this situation. A literature review with focus on qualitative studies was carried out to get a deeper insight and understanding of families who have a relative in intensive care unit. 15 qualitative studies have been analysed. For family members the situation is characterised by uncertainty, overwhelming feelings, as well additional responsibilities, and diverging family roles. Family members always put their ill relative in first place, and they do not articulate needs for themselves. They cope with this burdening situation by trying to be near to their relative, with or without being integrated into care. They search for honest information, get social support from significant others, and try to keep realistic hope all the time. The article also shows boundaries in this field of research, and discusses transferability and limitations of the findings. PMID- 20361406 TI - [The situation of people suffering from Parkinson's disease and their relatives in the mirror of literature - an overview]. AB - Despite of new therapy methods there currently is no perspective for healing or stopping the course of Parkinson's disease. Because of this and the predicted increase of the number of people suffering from parkinsonian syndromes, not only medical care but also nursing care of these syndromes will be of high importance in the future. The main objective of the conducted review was to study professional literature describing the situation of affected people and their relatives allowing to derive the appropriate requirements for a suitable care environment. This systematic review was conducted in the databases PubMed, CINAHL, Embase and Cochrane Library of Systematic Reviews. The results were considered with the focus of two main issues of a social situation (Dreitzel, 1972), the themes and the partners of interaction. The themes were assigned according to the coping needs of Corbin and Strauss (2004). Those needs can be observed during the progression of a chronic disease. Given the basic coping needs of affected people in different life situations, the results of 41 surveys and articles demonstrate the need for a continuous support of people suffering from parkinsonian syndromes and their relatives. Described are central issues such as financial coverage, maintenance of the individual role, getting support in dealing with the diagnosis and experiencing acceptance of one's perception of physical symptoms by health professionals. The professional life, family life, personal relationships, physician-patient and nurse-patient relationships, parent child relationships as well as being part of society are described to be particularly challenging. The importance of support by a specialised nurse within the meaning of a Parkinson's Disease Nurse Specialist is being discussed. PMID- 20361407 TI - [Lived experience and management of the every-day life after lower-limb amputation caused by vascular diseases]. AB - A lower limb amputation seriously restricts people's lives. Suddenly, they lose a crucial part of their body and their usual mobility. The main reason of lower limb amputation is diabetes mellitus. People living with a chronic illness have to face permanent uncertainty. There is little knowledge about the experience of living with a chronic illness, and suffering from a lower-limb amputation. This study examines how people with a lower-limb amputation caused by vascular diseases experience and manage their every-day life. Grounded Theory approach has been used to examine the research question. Qualitative interviews have been conducted with nine amputees, and data analysis has been done by using the method of Grounded Theory as well. As a result of an amputation, people have to cope with severe loss: the loss of a part of their body with consequences on their body image, the loss of mobility, a following dependency on means such as wheelchairs and prostheses, and the loss of the ability to manage daily activities. In order to be able to manage their daily activities again, amputees need to regain their mobility. At the same time, this regained mobility enables them to perform activities of individual importance within their disability. The results of this study help to understand the challenge of every-day live after a lower limb amputation caused by vascular diseases, which should serve for a basis of support for these people. PMID- 20361408 TI - [The discourse of the criteria for quality in qualitative research]. AB - Despite being a young discipline nursing science in the German-speaking area produces a growing number of research studies; many of them are qualitative in nature. Thus, it seems timely to raise questions about which quality criteria should be used to conduct and evaluate qualitative studies and to discuss how the scientific community in general and nursing science handle these issues. This article includes additional aspects of the recent quality discourse in German social and nursing science literature. For a better appraisal of the German speaking discourse it will be taken a short comparison with current articles of English-speaking journals. A terminal discussion of the main results follows. PMID- 20361409 TI - [Psychometric properties of Q-DIO, an instrument to measure the quality of documented nursing diagnoses, interventions and outcomes]. AB - The instrument Q-DIO was developed in the years 2005 till 2006 to measure the quality of documented nursing diagnoses, interventions, and nursing sensitive patient outcomes. Testing psychometric properties of the Q-DIO (Quality of nursing Diagnoses, Interventions and Outcomes.) was the study aim. Instrument testing included internal consistency, test-retest reliability, interrater reliability, item analyses, and an assessment of the objectivity. To render variation in scores, a random strata sample of 60 nursing documentations was drawn. The strata represented 30 nursing documentations with and 30 without application of theory based, standardised nursing language. Internal consistency of the subscale nursing diagnoses as process showed Cronbach's Alpha 0.83 [0.78, 0.88]; nursing diagnoses as product 0.98 [0.94, 0.99]; nursing interventions 0.90 [0.85, 0.94]; and nursing-sensitive patient outcomes 0.99 [0.95, 0.99]. With Cohen's Kappa of 0.95, the intrarater reliability was good. The interrater reliability showed a Kappa of 0.94 [0.90, 0.96]. Item analyses confirmed the fulfilment of criteria for degree of difficulty and discriminative validity of the items. In this study, Q-DIO has shown to be a reliable instrument. It allows measuring the documented quality of nursing diagnoses, interventions and outcomes with and without implementation of theory based, standardised nursing languages. Studies for further testing of Q-DIO in other settings are recommended. The results implicitly support the use of nursing classifications such as NANDA, NIC and NOC. PMID- 20361411 TI - It's never too late to get physical. PMID- 20361413 TI - No more nosebleeds. PMID- 20361412 TI - Lusher lashes, but at real risk. PMID- 20361414 TI - An adrenal mass. PMID- 20361415 TI - Successful radiation therapy for cerebral metastatic lesions from a pheochromocytoma. PMID- 20361416 TI - Cushing syndrome related to gingival application of a dexamethasone-containing preparation. PMID- 20361417 TI - Pheochromocytoma in pregnancy. PMID- 20361418 TI - In this Issue: Inflammation. AB - We live in a microbial world and are often confronted with infection and injury. Inflammation, the response that is unleashed to ward off these insults, has long been familiar to us. Indeed, the words that we still use to describe inflammation -redness and swelling with heat and pain -were coined in the first century A.D. by the Roman physician Cornelius Celsus: rubor et tumor cum calore et dolore. The word inflammation itself comes from the Latin inflammare: to set on fire. Research has taken us a long way from this first description of the overt symptoms of inflammation 2000 years ago to our current understanding of the molecular and cellular pathways that mediate the inflammatory process, regulate it, and lead to its resolution. We now know that inflammation can come in many forms and modalities depending on the context in which it is triggered, the trigger itself, and the tissues involved. Furthermore, we appreciate the contribution of inflammation to cancer and to chronic afflictions like neurodegenerative diseases and diabetes. In this year's Special Review Issue, we bring together Review articles and Essays that survey our current knowledge of inflammation and provide perspectives on the key questions and challenges ahead. We would like to thank the distinguished experts who contributed their time and effort as authors and reviewers to make this issue timely, comprehensive,and thought provoking. We hope that this collection of articles will be informative and inspiring, as we now harness the tools of modern biology in the continued effort to understand :"the old flame". PMID- 20361419 TI - Differentials in sex ratio at birth among natives and immigrants in Greece: an analysis employing nationwide micro-data. AB - This study uses micro-level information on the live births registered in Greece for 2006 to assess differentials in the propensity to have a male offspring between natives and immigrants. The sex ratio at birth for the whole population is 106.3 but it is considerably higher among immigrants (110.9) than among natives (105.4). Relatively high sex ratios at birth are observed for several migrant groups; differentials between natives, on the one hand, and Albanians (109.5) and Asians (129.0), on the other, are significant. The high sex ratio at birth for Albanians seems typical of that population. For Asians, the result is consistent with international findings though it may also be partly related to the small number of observations. PMID- 20361420 TI - Wolff-Parkinson-White syndrome in a child with recurrent seizures. PMID- 20361421 TI - Ebstein's malformation presenting with tricuspid stenosis: 1-year follow-up after surgical repair. AB - This is a case of a young woman previously completely healthy, with two uneventful pregnancies and deliveries, who presented with bloating, shortness of breath, and signs of right heart failure. A thorough clinical evaluation, along with a work-up including an echocardiogram and a magnetic resonance imaging revealed the diagnosis of Ebstein's anomaly malformation with tricuspid stenosis. A right ventricular outflow tract obstruction due to thrombus formation was thought to exacerbate her symptoms and lead to the diagnosis. Surgery in the form of right ventricular thrombectomy, right atrial reduction, porcine tricuspid valve replacement and bidirectional cavopulmonary anastomosis "bidirectional Glenn", was successfully performed. The patient has been stable clinically more than one year after surgery. Discussion about this rare condition and operative details are provided. PMID- 20361422 TI - My parents' dance. PMID- 20361423 TI - Incidence of childhood cancer in France: National Children Cancer Registries, 2000-2004. AB - The French National Registry of Childhood Haematopoietic Malignancies and the French National Registry of Childhood Solid Tumours jointly ensure the surveillance of cancer in children aged less than 15 years in mainland France. During the period 2000-2004, the registries recorded a total of 8473 cases: 3446 cases of haematological malignancies and 5027 cases of solid tumours. The average number of sources per case was 2.7 and diagnosis was documented by cytology/histology in 94% of cases, ensuring high quality data. The age standardized incidence rate for all cancers combined was 156.6 cases per million children per year, with a sex ratio of 1.2. The most frequent cancers were leukaemia (29%), central nervous system tumour (23%), lymphoma (12%) and neuroblastoma (8%). In France, an estimated one out of every 440 children presents with cancer before the age of 15 years. The incidence rates are close to those of other industrialized countries, but somewhat higher than those estimated by the French local registries for the period 1990-1999, probably because of improved methodology or perhaps a real increase in some rates. The French National Registries of Childhood Cancer have shown that they are able to fulfil public health surveillance missions satisfactorily and support the national programme for research on childhood cancer. PMID- 20361424 TI - Opioids affect focal contact-mediated cell-substrate adhesion. AB - Earlier observations suggested that opioids modify cell-substrate adhesion on agar. In this study, we wanted to investigate whether opioids also interfere with cell adhesion to biologically relevant substrates, including interstitial matrix and basement membrane components. Human embryonic kidney 293 cells stably transfected with FLAG-tagged micro-opioid receptor were used as an experimental model. The cells were cultured on tissue culture plastic, collagen types I and IV, fibronectin, laminin and human amnion fragments in the absence or presence of morphine. Cultures were immunolabelled with antivinculin to visualize focal contacts. Morphine-treated cultures on tissue culture plastic, collagen types I and IV and fibronectin, but not on laminin, covered less substrate than untreated cultures; individual cells were difficult to distinguish and their nuclei piled up in contrast to untreated cultures. The same effects were observed on human amnion fragments: morphine changed the morphotype of cultures on the stromal side, but not on the basement membrane side. Cultures that were treated with morphine displayed fewer focal contacts than untreated cultures on collagen type I, whereas untreated and morphine-treated cultures were indistinguishable on laminin. PMID- 20361425 TI - Show a little kindness. PMID- 20361426 TI - Show me the evidence. PMID- 20361427 TI - Hold on to the profession. PMID- 20361428 TI - Critical aspects in the use of injectable calcium phosphates in spinal surgery. PMID- 20361429 TI - Bored to death? PMID- 20361430 TI - Special crash investigations--a model for future corrective action: first generation frontal air bags. PMID- 20361431 TI - Analysis of cardiac development. Issue dedicated to the memory of Sam Sideman. PMID- 20361432 TI - Current awareness in drug testing and analysis. PMID- 20361433 TI - Cause and effect. AB - The experimental tractability of biological systems makes it possible to explore the idea that causal relationships can be estimated from observational data. PMID- 20361434 TI - [Central water supply in Berlin and Istanbul: a comparison of processes of introduction, diffusion, and acceptance]. PMID- 20361435 TI - New Frontiers in Respiratory Control. Proceedings of the XIth Annual Oxford Conference in Modeling and Control of Breathing, Nara, Japan, 23-26 July, 2009. PMID- 20361436 TI - [Musculoskeletal tumors. I. Therapeutic strategy for desmoid -type fibromatosis- positioning of chemotherapy]. PMID- 20361437 TI - [Musculoskeletal tumors. II. Therapeutic strategy for vascular sarcoma--with special reference to the recent progress in chemotherapy]. PMID- 20361438 TI - [Musculoskeletal tumor. III. Chemotherapy of liposarcoma--the current status of chemotherapy and new findings in clinical trials of novel drugs]. PMID- 20361439 TI - Securing the future of children's health. PMID- 20361440 TI - Magic as a therapeutic intervention to promote coping in hospitalized pediatric patients. AB - Magic as a therapeutic intervention is used in an innovative, hospital-based program to address the psychosocial issues children and adolescents often experience as a result of illness and hospitalization. A child life specialist and a magician with an MBA collaborated, blending clinical expertise with business acumen and professional-level magic skills to create the program. The program has two distinct components: (1) magicians using interactive, close-up magic and humor as a technique to promote socialization, enhance self-esteem, and increase opportunities for choice and control, and (2) magicians providing the personal instruction and materials that enable chronically ill and long-term patients to learn and perform magic to promote a sense of empowerment and feelings of mastery. Positive responses from patients, families, and staff to the program at one hospital led to the creation of Open Heart Magic, a non-profit children's foundation that maintains and staffs bedside, interactive therapeutic magic programs in five hospitals in the Chicago metropolitan area. PMID- 20361441 TI - Community environmental quality knowledge and awareness among nurses: developing and piloting an assessment survey in schools. AB - About one in five Americans spends a considerable number of hours in school each week, and thus, is exposed to a variety of environmental agents. Community health nursing professionals require resources and specific training to acquire the environmental knowledge needed to raise personal and community awareness as an enhancement of their practice. Given limited resources for schools and local public health education initiatives, identifying and prioritizing environmental concerns comes before actions to prevent or reduce exposures. With the rise in prevalence of childhood asthma, of special concern are those agents within the school environment that may serve as asthma triggers. This pilot project, within a larger study in a large school district in metropolitan Atlanta, Georgia, developed and piloted an environmental health priorities survey with school nurses and other school staff about indoor and outdoor microenvironments relevant to school-aged children. Findings indicate that participants (N = 34) could prioritize environmental issues to inform future intervention activities (such as continuing education training), and distinguish predominantly indoor from typical outdoor exposure agents and their major sources. PMID- 20361442 TI - Outdoor air pollution and children's health. AB - Children spend almost 90% of their time indoors, though outside air can be a significant source of potential and actual exposure to outdoor air pollutants. Children are vulnerable to pollutants and toxins because of their size and developing organ systems. Young children have increased respiratory rates and inhale more toxins, and young children often ignore respiratory symptoms and continue play. Outdoor play and recreational activities expose children to outdoor air pollution from sources such as automobiles, power plants, industry, and other combustion sources, which can impact children. Outdoor air pollution has been linked to respiratory illness exacerbations, infant mortality, the development of asthma, and atopy and reduction in lung development in children. This article will examine outdoor air pollution and its impact on children's health, as well as implications for pediatric nursing clinical practice. PMID- 20361443 TI - Incorporating environmental health into nursing practice: a case study on indoor air quality. AB - More than one-quarter of the global disease burden is attributable to environmental exposures, with children bearing a disproportionate amount of risk. Physiologically and behaviorally, children have unique characteristics that make them vulnerable to environmental contaminants. In particular, indoor environmental exposures, such as carbon monoxide, mold, and radon, have an impact on children's health and well being. A case study based on the experiences of nurses working on the Environmental Risk Reduction through Nursing Intervention and Education study is presented to illustrate multiple exposures children may face in the home environment and the role nurses play in prevention and response. Nurses can improve children's environmental health by providing risk assessments, environmental health education, and referrals to community health nurses and environmental health specialists. Resources on indoor air quality and maintaining a healthy home are provided. PMID- 20361444 TI - Nurse practitioner role in preparing families for pediatric outpatient surgery. AB - Due to medical advances in surgery and anesthesia and cost of hospital stays, more elective pediatric surgical procedures are being performed in outpatient settings. One proposed advantage of outpatient surgery is decreased anxiety or a shorter period of anxiety for pediatric patients and their families because they are able to go home shortly after the surgery. A literature review was conducted to describe anxiety experienced by pediatric patients and their families in the outpatient surgery setting and to explore ways to decrease that anxiety. Both children and parents reported not feeling emotionally and educationally prepared for outpatient surgery. Developmentally appropriate pre-surgical educational programs and parental involvement in the surgical experience can help alleviate the anxiety of both children and parents during the pediatric surgical experience. Nurse practitioners (NPs) are currently being used in pre-operative outpatient settings to conduct physical examinations and provide pre-op education. Pre-op education programs provided by NPs are beneficial in decreasing the anxiety state among children and parents prior to surgery. PMID- 20361445 TI - Pediatric dental erosion and extraesophageal reflux disease: a case presentation. PMID- 20361446 TI - Care of the child with the desire to change gender--Part I. AB - This article is the first in a three-part series describing the nursing and medical care of a child wishing to change genders. Part I will depict the psychological and hormonal treatment for children who express a desire to change genders. Part II will describe surgical treatments and nursing care for gender reassignment from female to male. Part III will present the surgical needs of transition from male to female. PMID- 20361447 TI - Pediatric palliative and hospice care: Pennsylvania's model of collaboration. AB - In the state of Pennsylvania, a collaborative model has been developed for improving pediatric palliative care and end-of-life care services to children with life-limiting conditions and their families. The inspiration and efforts of several bereaved parents provided the initial impetus for this encouraging model. Pennsylvania's model involves cooperation and collaboration among several groups and initiatives across the state, as well as the integration of parent professional collaboration at all levels and in each initiative. The collaborating groups include 1) a volunteer grassroots resource and education initiative, Helping Hands-Healing Hearts; 2) the Pittsburgh Pediatric Palliative Care Coalition, a coalition of concerned parents and experienced palliative and hospice care providers working together to improve service availability; and 3) the Pennsylvania Children's Hospice and Palliative Care Coalition, which developed as an outcome of a state-level Pennsylvania Pediatric Hospice Care Task Force, and which, among other activities, works with the Pennsylvania Department of Public Welfare and several Pennsylvania legislators on pertinent policy and legislative initiatives. PMID- 20361452 TI - Chief nurse resigns...and reflects. Interview by Teresa O'Connor. PMID- 20361453 TI - Improving the patient experience in Canterbury--a vision for the future. PMID- 20361454 TI - Facilitating student learning in clinical practice. PMID- 20361455 TI - Students reflect on medico-legal forum. PMID- 20361456 TI - Should student nurses take blood? PMID- 20361457 TI - Good work/hard work. PMID- 20361458 TI - Regaining renewed respect for nursing. PMID- 20361459 TI - Realising opportunities for growth. PMID- 20361460 TI - Commitment and action build loyalty and effectiveness. PMID- 20361461 TI - From Idaho to Invercargill. Interview by Teresa O'Connor. PMID- 20361462 TI - NZNO's services for students. PMID- 20361463 TI - Members consider an alternative bargaining strategy. PMID- 20361464 TI - A multidisciplinary approach to neoadjuvant therapy for primary operable breast cancer. Challenges and opportunities. AB - Neoadjuvant therapy may provide advantages to some women with primary operable breast cancer. Compared to the administration of the same regimen in the adjuvant setting, neoadjuvant chemotherapy does not improve survival outcomes, but may provide other benefits. Neoadjuvant therapy is associated with improved rates of breast-conserving therapy, may offer prognostic information, and enables assessment of in vive response to therapy. Women who achieve a pathologic complete response following neoadjuvant therapy are expected to have a superior outcome compared to those with extensive residual disease. The neoadjuvant setting has been an attractive area of research for identifying new effective treatment strategies while minimizing treatment-related adverse events, studying drug mechanisms of action, and developing clinically applicable prognostic and predictive biomarkers in an attempt to individualize therapy. In the primary operable setting, it is of great importance to define treatment goals, to select proper candidates for the approach, to assess baseline tumor characteristics, and to provide optimal multidisciplinary monitoring during and following the neoadjuvant therapy. PMID- 20361465 TI - Clarifying the role of neoadjuvant therapy in breast cancer. PMID- 20361466 TI - Monoclonal antibodies in advanced B-cell lymphomas. AB - The treatment of B-cell malignancies has been revolutionized by the availability of safe and effective monoclonal antibodies. The addition of rituximab to standard chemotherapy regimens prolongs the survival ofpatients with diffuse large B-cell lymphoma (DLBCL) and follicular non-Hodgkin lymphoma. Nevertheless, indolent and mantle cell lymphomas remain incurable, and 30% to 40% of patients with DLBCL still die from their disease. Much ongoing research has focused on optimizing monoclonal antibody use, integrating them into multiagent regimens, and developing newer antibodies. Attempts to improve on the efficacy of monoclonal antibody-based therapy have included altering the dosing schedule, optimizing patient selection, maintenance therapy, improving upon the rituximab molecule, radioimmunotherapy, as well as combinations with cytotoxic molecules and other novel agents. Preliminary data with a number of treatment regimens are promising in indolent and aggressive lymphomas. The eventual goal of targeted therapies is to individualize treatment to increase response and survival, while reducing treatment-related toxicity. PMID- 20361467 TI - 'Vitamin R' and its younger siblings. PMID- 20361468 TI - Improving our use and understanding of antibodies in B-cell lymphomas. PMID- 20361469 TI - HDAC inhibitors in cancer care. AB - The epigenetic control of gene expression has been shown to play an important role in cancer initiation, progression, and resistance. Thus, agents that modify the epigenetic environment of tumors will likely be an important addition to the anticancer arsenal. Specifically, there is much interest in modulating histone acetylation using a new class of drugs, histone deacetylase (HDAC) inhibitors. Preclinical data have demonstrated the efficacy of various HDAC inhibitors as anticancer agents, with the greatest effects shown when HDAC inhibitors are used in combination with other therapies. As a result of encouraging preclinical data, numerous HDAC inhibitors are being investigated in clinical trials either as monotherapies or in conjunction with other treatments such as chemotherapy, biologic therapy, or radiation therapy. In fact, vorinostat and depsipeptide, two actively studied HDAC inhibitors, were recently approved for the treatment of refractory cutaneous T-cell lymphoma. Although the use of HDAC inhibitors has generated great enthusiasm, a significant amount of work still needs to be done in order to understand their mechanisms of action, as well as to determine the appropriate patient characteristics and subsets of cancer for which HDAC inhibitors hold the most potential for effective treatment. PMID- 20361470 TI - HDAC inhibitors: much to learn about effective therapy. PMID- 20361471 TI - HDAC inhibitor research: still in its infancy. PMID- 20361472 TI - Fighting a smarter war on cancer. PMID- 20361473 TI - Gerson regimen. AB - The Gerson regimen, developed by Max Gerson in the 1930s, is promoted as an alternative cancer treatment. It involves consuming fresh, raw fruit and vegetable juices, eliminating salt from the diet, taking supplements such as potassium, vitamin B12, thyroid hormone, pancreatic enzymes, and detoxifying liver with coffee enemas to stimulate metabolism. Gerson therapy is based on the theory that cancer is caused by alteration of cell metabolism by toxic environmental substances and processed food, which changes its sodium and potassium content. It emphasizes increasing potassium intake and minimizing sodium consumption in an effort to correct the electrolyte imbalance, repair tissue, and detoxify the liver. The coffee enemas are believed to cause dilation of bile ducts and excretion of toxic breakdown products by the liver and through the colon wall. None of these theories has been substantiated by scientific research. Despite proponents' claims of recovery rates as high as 70% to 90%, case reviews by the National Cancer Institute (NCI) and the New York County Medical Society found no evidence of usefulness for the Gerson diet. An NCI sponsored study of Gonzalez therapy, which is similar to the Gerson diet, showed that patients with inoperable pancreatic adenocarcinoma who underwent standard chemotherapy with gemcitabine (Gemzar) survived three times longer and had better quality of life than those who chose enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. PMID- 20361474 TI - Practical applications of a new botulinum toxin. AB - The injection of Clostridium botulinum type A neurotoxins is among the most commonly performed cosmetic procedures, both in the U.S. and worldwide. The U.S. Food and Drug Administration (FDA) approval of a new botulinum neurotoxin type A in April 2009 (BoNT-A, Dysport, Medicis, Scottsdale, AZ-hereafter referred to as "Dysport") has broadened the neurotoxin market and provides new therapeutic alternatives to practitioners. The introduction of this product raises questions about how to best use it. In this supplement, the authors address critical similarities and differences between onabotulinumtoxinA (Botox, Allergan, Irvine, CA--hereafter referred to as "Botox") and abobotulinumtoxinA (Dysport). The authors also provide practical guidelines for the use of Dysport based on clinical experience and peer-reviewed, published clinical trials. In the authors' opinion, Botox and Dysport can be used for similar "on-" and "off-label" applications. Judicious use of either product requires an understanding of how the two products differ in order to avoid side effects and achieve optimal results. Common Questions: Are these two toxins the same or different and how? How are inter-product "unit" conversions addressed? Does injection technique differ? Does one product result in greater adverse events? Does one product last longer or "diffuse" better than the other? What other toxins can be expected on the market in the future? PMID- 20361475 TI - [Second symposium on cardiac arrhythmias. Preface]. PMID- 20361476 TI - [Uncomplicated and complicated myocardial peripheral blocks]. AB - Septal necrosis + peripheral left blocks. Because of an extensive septal necrosis, the manifestation of the initial ventricular activation forces decreases in the precordial leads. With left bifascicular block (LASB + LPSB), the first ventricular activation forces become more evident and the electrical signs of septal necrosis can be concealed. In the presence of a trifascicular block, the manifestation of the first ventricular electromotive forces diminishes again and the electrical signs of septal necrosis become evident once more. Small Q waves are present in leads V1 to V4. Extensive anterior necrosis + left peripheral blocks. This necrosis is manifested by QS complexes from V2 to V6. An associated left bifascicular block reduces the electrical manifestation of dead tissue: QS complexes persist only in V3 and V4. In turn, a coexisting trifascicular block causes the presence of QS complexes from V2 to V5. Posteroinferior necrosis + left peripheral blocks. Electromotive forces of the ventricular activation shift upward, due to a posteroinferior necrosis, and QS or QR complexes are recorded in leads aVF, II and III. An associated left bifascicular block displaces the main electromotive forces downward, posteriorly and to the left, due to a delay of the posteroinferior activation fronts. The ventricular complexes become positive and wider in all leads, reflecting the potential variations of the inferior portions of the left ventricle: aVF, II, III, sometimes V5 and V6. Consequently, the electrical signs of necrosis are reduced or abolished. Right ventricular peripheral blocks do not conceal the electrocardiographic signs of univentricular and biventricular dead myocardium. PMID- 20361477 TI - [Genetic of catecholaminergic polymorphic ventricular tachycardia: basic concepts]. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts. Patients present with exertional syncope and the trademark dysrhythmia is polymorphic and/or bidirectional ventricular tachycardia during exercise or adrenergic stimulation. Early detection of CPVT is crucial because opportune medical intervention prevents sudden cardiac death. Mutations in the ryanodine receptor RYR2 explain nearly 70% of the CPVT cases and cause the autosomic dominant form of the disease. Mutations in calsequestrin 2 causes a recessive form and explain less than 5% of all cases. Genetic screening in CPVT, besides providing early detection of asymptomatic carriers at risk, has provided important insights in the mechanism underlying the disease. Mutational analysis of RYR2 has been a challenge due to the large size of the gene, 105 exons encoded for 4,967 amino-acids. In this review we analyze general concepts of the disease, differential diagnosis and strategies for genetic screening. PMID- 20361478 TI - [Recent advances in the pathophysiology of atrial fibrillation]. AB - This review is a summary of the pathophysiology of atrial fibrillation (AF) and the progress in the understanding of this arrhythmia. The following factors should be considered in the genesis and maintenance of AF. The genetic factor is involved in cases of familial AF. Predisposing structural factors: atrial dilation, structural feature that allows the development of AF. Predisposing structural factors: the role of the Bachmann's bundle and frequency gradients between the left and right atrium. Electrophysiological factors: heterogeneous refractory periods favor the fibrillatory conduction. Triggers: abnormal electrical activity (ectopic foci). Modulating factors: autonomic nervous system. Increased vagal tone shortens atrial refractory periods, creating a greater dispersion of the refractory periods and the generation of reentries in the context of triggered activity. Finally, there are three types of atrial remodeling secondary to AF: structural, contractile, electrical. They are interrelated and contribute to maintaining the AF ("AF begets AF"). PMID- 20361479 TI - [Genetic in long QT syndromes]. AB - The long QT syndrome (LQTS) is a genetic disorder characterized by prolongation of the QT interval in the electrocardiogram (ECG) and a propensity to "torsades de pointes" ventricular tachycardia frequently leading to syncope, cardiac arrest, or sudden death usually in young otherwise healthy individuals. LQTS caused by mutations of predominantly potassium and sodium ion channel genes or channel-interacting proteins leading to positive overcharge of myocardial cell with consequent heterogeneous prolongation of repolarization in various layers and regions of myocardium. These conditions facilitate the early after depolarization and reentry phenomena underlying development of polymorphic ventricular tachycardia observed in patients with LQTS. Obtaining detailed patient history regarding cardiac events in the patient and his/her family members combined with careful interpretation of standard 12-lead ECG (with precise measurement of QT interval in all available ECGs and evaluation of T-wave morphology) usually is sufficient to diagnose the syndrome. The LQTS show great genetic heterogeneity and has been identified more than 500 mutations distributed in 10 genes: KCNQ1, HERG, SCN5A, KCNE1, KCNE2, ANKB, KCNJ2, CACNA1A, CAV3 and SCN4B. Despite advances in the field, 25-30% of patients remain undiagnosed genetic. Genetic testing plays an important role and is particularly useful in cases with nondiagnostic or borderline ECG findings. PMID- 20361480 TI - [Diagnosis of tachycardias in pediatric patients]. AB - Arrythmias in the pediatric patient usually are considered rare; nonetheless, their number is increasing. The paroxistic supraventricular tachycardia is the most frequent symptomatic arrhythmia. The diagnosis is based on electrocardiographic register. There are few diagnostic tools including the Hotter monitoring and loop recorders. Once the tachychardia is detected, a deductive electrocardiographic diagnosis and specific treatment are established. PMID- 20361481 TI - [Neurocardiogenic syncope in children]. AB - The diagnosis of neurocardiogenic syncope in the pediatric patient is increasing in frequency. The difficulty to diagnose in the pediatric group of age is greater because of their lack of communication skills to describe the symptoms or to identify them, and thus the reason why in many cases neurologic and cardiac studies are performed to discard other pathologies, before suspecting the diagnosis of vasdvagal syncope. A thorough physical exam and the use of adequate resources for diagnosis are key factors for appropriate treatment. This is based principally in general measures and depending on the results of the head up tilt test, pharmacological treatment can be administered, even though optimal treatment is still in universal discussion. PMID- 20361482 TI - [Utility of high parasternal electrocardiographic leads in the diagnosis of Brugada syndrome]. AB - The use of high right precordial (HPL) leads to "unmask" Brugada syndrome (BrS) has been described by some groups. We report a family with three cases of BrS. In two, HPL were obtained by placing V1 to V3 electrodes on the first, second, and third right parasternal spaces, and V4 to V6 on the first, second, and third left parasternal spaces. A control group of 45 subjects without BrS was also studied. Compared with standard V1 and V2 leads, the abnormal repolarization pattern of the BrS was accentuated only in the BrS cases using HPL. In none of the control subjects alterations of the J point or ST segment were observed in HPL. These observations exemplify the relevance of HPL for the diagnosis of the BrS. PMID- 20361483 TI - [Interventional treatment of typical atrial flutter]. AB - OBJECTIVES: To inform the efficacy and safety of the interventional treatment of typical atrial flutter (AFL). AFL is a common arrhythmia that has a characteristic pattern on 12-lead ECG. The unique endocardial anatomy of the right atrium, with its many orifices and distinct structures provides anatomic barriers around which reentry could occur, likely explains the consistency of AFL from patient to patient. Much of our current understanding of the role of barriers in AFL has been from animal models. Using multisite endocardial mapping in patients with AFL, activation in the right atrium spreads superiorly from the coronary sinus ostium, up the septum and down the lateral right atrial wall (counterclockwise rotation of typical flutter and clockwise in reverse typical AFL). METHODS: A critical area of slow conduction was identified between the coronary sinus ostium, tricuspid valve ring, and inferior vena cava (the cavotricuspid isthmus). Entrainment has also been used to interrogate the AFL circuit. Concealed entrainment demonstrates that typical AFL is a reentrant arrhythmia and it has been demonstrated in the area of cavotricuspid isthmus. AFL is an arrhythmia that can be cured by catheter ablation of the tricuspid valve inferior vena cava isthmus. The aim of catheter ablation for typical AFL is to create a complete and stable bidirectional cavotricuspid isthmus block. Ablation is performed during AFL or sinus rhythm, using either an 8/10 mm tip catheter or an irrigated tip catheter. RESULTS: After ablation, assessment of cavotricuspid isthmus conduction is performed periodically to confirm a complete and stable bidirectional block. With this primary end-point, the long-term efficacy has increased to >90% with low recurrence rate. CONCLUSIONS: Ablation of AFL is safe and effective, improved quality of life and has a minimal risk of adverse effects. Catheter ablation is now considered as alternative first line therapy for all those with symptomatic sustained typical AFL. PMID- 20361484 TI - [Electroanatomic mapping and radiofrequency catheter ablation of focal atrial tachycardias]. AB - Focal atrial tachycardia is defined as supraventricular tachycardia originating from discrete sites from which activation spreads to both atrial. In most clinical series, atrial tachycardia account for about 5% of all supraventricular arrythmias. This tachycardia can occur in children or adults within and without structural heart disease. Three potential mechanisms are described for its origin: abnormal automaticity, triggered activity or microreentry. Catheter ablation has an important role in the management of focal atrial tachycardia and is now considered to be a first line therapy, can be improved with electroanatomical mapping system (CARTO) that allows reconstruction of the chamber geometry and allow visualization of the activation sequence; and can to improve the efficacy of catheter ablation. PMID- 20361485 TI - [Catheter ablation of monomorphic sustained ventricular tachycardia]. AB - The interventional treatment of arrhythmias with catheter ablation have become the first line therapy for a significant number of tachyarrithmias, offering curative treatment in the majority of them. Ventricular arrhythmias form a group of great interest for the interventional electrophysiologist, because in contrast to the traditional thought, today we can identify some sub-groups of monomorphic sustained ventricular tachycardia (MSVT) with very good percentages of cure, whereas others like those with ischemic etiology ablation is still a palliative procedure. In this paper we will review the different types of MSVT, its etiology and therapeutic options from the interventionist point of view. PMID- 20361486 TI - [Echocardiographic assessment of ventricular synchrony. Implications to patient selection and treatment outcome]. AB - Heart failure is one of the most prevalent diseases in industrialized countries. Up to 30% of the patients with advanced heart failure present disturbances in intra-ventricular conduction, and this produce asynchrony of ventricular contractility, leading to further deterioration in heart function. Cardiac resynchronization (TRC) is an increasingly important therapeutic option for a subgroup of patients with heart failure. Several methods have been show to be useful in study the mechanical asynchrony. However, there are discrepancies between the results of the different methods. The echocardiography provides the best parameters in predicting a good response. PMID- 20361487 TI - [Clinical benefit in cardiac resynchronization]. AB - Despite the improvement in pharmacologic treatment of heart failure, many patients continue to have severe persistent symptoms, and their prognosis remains poor. One of the most recent advances in heart failure management is the concept of cardiac resynchronization therapy (CRT). Large clinical trials have demonstrated morbidity and mortality benefits of CRT in patients with moderate to severe drug refractory heart failure (New York Heart Association [NYHA] functional class III or IV), and ejection fraction < or = 35% with QRS duration > or = 120 ms. PMID- 20361489 TI - [The methodological problem in experimental medicine]. PMID- 20361488 TI - [Remote wireless monitoring]. AB - The increasing device implantations to treat cardiovascular diseases such as arrhytmias and heart failures, aging of the population, and the growing number of patients with access to new therapies as well as the wider access to health systems are the reasons why the number of new implantations carried out each year is rising. Hence, we should have an equipment that can control these patients at a distance, making the follow-up closer. The answer to this enormous challenge is the remote monitoring of these devices. Biotronik is a pioneer in this task and since 2001 it has been comercializing pacemakers and portable wireless monitors (CardioMessenger). Currently, there are more than 100,000 installed systems. Thanks to the continuous and completely automatized follow-up, as well as the wireless net, the system integrity can be confirmed, and then proceed to adjust the therapies in an optimized manner according to each patient's needs; also take action to prevent the development of some arrhytmias, or even the evolution of a heart failure. Likewise, the system can improve the clynical efficiency of the treatment and help to economize to the Ministry of Healthcare. PMID- 20361490 TI - [Role of serotonin receptors in vascular tone in the pithed rat]. AB - Serotonin (5-hydroxytryptamine; 5-HT) has been shown to produce vascular sympatho inhibition in a wide variety of isolated blood vessels by activation of prejunctional 5-HT1 receptors. After considering the mechanisms involved in modulating neuroeffector transmission, the present review analyzes the experimental findings identifying the pharmacological profile of the 5-HT receptors that inhibit the sympathetically-induced vasopressor responses in pithed rats. Thus, 5-HT-induced sympatho-inhibition has been shown to be: (i) unaffected by physiological saline or by the selective antagonists ritanserin (5 HT2), MDL72222 (5-HT3) or tropisetron (5-HT3/4); (ii) blocked by methysergide, a non-selective 5-HT1/2 receptor antagonist; and (iii) potently mimicked by 5 carboxamidotryptamine (5-CT), a non-selective 5-HT1 receptor agonist, as well as by the selective agonists 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP93,129 (5 HT1B), and sumatriptan (5-HT1B/1D). These findings show the involvement of prejunctional 5-HT1 receptors. With the use of selective antagonists, it has been shown subsequently that the sympatho-inhibition induced by indorenate, CP93, 129, and sumatriptan was selectively antagonized by WAY100635 (5-HT1A), cyanopindolol (5-HT1A/1B), and GR127935 (5-HT1B/1D), respectively. These results demonstrate that the 5-HT1 receptors mediating sympatho-inhibition on the systemic vasculature of pithed rats resemble the pharmacological profile of the 5-HT1A, 5 HT1B, and 5-HT1D subtypes. PMID- 20361491 TI - [On Mexican medicinal plants]. AB - During the XVIII century, two Spanish scientific expeditions arrived here led, respectively, by the naturalist Martin Sesse and by the Italian mariner Alessandro Malaspina di Mulazzo, dependent from the Spanish Government. The members collected a rich scientific material, which was carried to Madrid in 1820. At the end of XVIII century, the Franciscan friar Juan Navarro depicted and described several Mexican medicinal plants in the fifth volume of his "American Garden". In the last years of the Colonial period, fundamental works of Humboldt and Bonpland, on the geographic distribution of the American plants, were published. At the end of the XIX century, the first researches on the Mexican medicinal botany were performed at the laboratory of the "Instituto Medico Nacional" under the leadership of doctor Fernando Altamirano, starting pharmacological studies in our country. During the first half of the XX century, trials of cardiovascular pharmacology were performed in the small laboratories of the cardiological unit at the General Hospital of Mexico, due to doctor Ignacio Chavez, initiative. Mexican botanical-pharmacological tradition remains alive and vigorous in the modern scientific institutes of the country. PMID- 20361492 TI - [Platelet abnormalities in type 2 diabetes mellitus]. AB - Diabetes mellitus is a problem of health worldwide being vascular complications the main causes of morbidity and mortality in this population. Diabetics have a fast atherothrombotic evolution which is worse than that observed for other clinical entities; however, hyperglycemia itself may not totally explain the ischemic complications observed in these patients. Most ischemic arterial events are precipitated by plaque rupture, platelet activation, and thrombosis. Several abnormalities in the blood coagulation system have been described associated to diabetes mellitus, all of them predisposing to thrombosis: endothelial cell dysfunction, platelet hyperreactivity, thrombin generation and hypofibrinolysis. Platelets play a key role in diabetic atherothrombosis due to platelet hypersensitivity to physiological agonists, low response to therapeutical antiplatelet agents, platelet hyperreactivity in sites of endothelial cell damage, hyperaggregability, resistance to the inhibitory effects of the insulin, and low endothelial production of prostacyclin and nitric oxide. All these phenomena have been associated to either a toxic microenvironment due to hyperglycemia or to intrinsic platelet abnormalities. Based on all these facts, it is proposed that platelets may be another target for the negative effects of insulin-resistance state. Because platelets are crucial in the atherosclerotic process and in the genesis of the vascular complications of diabetes mellitus, this review analyses the platelet abnormalities observed in this metabolic disease. PMID- 20361493 TI - [Neural control of the peripheral circulation and blood pressure]. AB - In the XIX century Claude Bernard discovered the action of the nervous system on the peripheral circulation. In the first half of the XX century Ewald Hering discovered the baro-receptor and the reflex control of the heart rate and blood pressure. Cowley and Guyton demonstrated that sino-aortic denervation induces persistent changes in the blood pressure in the dog. The autonomic nervous system is mainly responsible for the regulation of the circulation and blood pressure in the short term on a beat to beat basis. It controls the vasomotor tone, the heart rate and the cardiac output. With the advent of non invasive methods that measure the blood pressure on a beat to beat basis (Finapres) and with the methods of measurement of the variability of the blood pressure in the frequency domain (spectral analysis) we can currently measure many variables including heart rate, blood pressure, stroke volume, peripheral resistances and the baroreceptor sensitivity and make some inferences about their control mechanisms. These variables can be measured at rest in the supine position, standing up, during rhythmic breathing and during the Valsalva maneuver. In this article we present a review of the neural control of the blood pressure and heart rate. PMID- 20361494 TI - Arbuscular mycorrhizal fungal propagules from tillage and no-tillage systems: possible effects on Glomeromycota diversity. AB - Arbuscular mycorrhizal fungi (AMF) can use different types of propagules to colonize new roots. In this work we tested different types of AMF inocula obtained from a field experiment with tilled and no-tilled soils planted with wheat as well as from nondisturbed treatments with spontaneous vegetation. AMF trap cultures were carried out with soil, mycelium, segments of roots and wheat plants from the field as sources of inocula. Then after the senescence of the trap plants Glomeromycota species that had been established from each type of propagule in the substrate from the pots were identified. In field soils the proportions of Acaulosporaceae and Gigasporaceae were relatively similar to that of Glomeraceae, mainly in conventional tillage, whereas in all trap cultures investigated the percentages of members of the Glomeraceae family were higher than 90%. Because most of the trap cultures were based on intra- and/or extraradical mycelium our results show that members of Glomeraceae have advantages in the use of these propagules over Acaulosporaceae and Gigasporaceae species. We suggest that the higher contribution of Glomeraceae previously found in no-tillage systems could be related partially to the lack of disruption of the hyphal network and the composition of the soil propagules in this system. PMID- 20361495 TI - The diversity and evolution of circadian clock proteins in fungi. AB - Circadian rhythms are endogenous cellular patterns that associate multiple physiological and molecular functions with time. The Neurospora circadian system contains at least three oscillators: the FRQ/WC-dependent circadian oscillator (FWO), whose core components are the FRQ, WC-1, WC-2, FRH, and FWD-1 proteins; the WC-dependent circadian oscillator (WC-FLO); and one or more FRQ/ WC independent oscillators (FLO). Little is known about the distribution of homologs of the Neurospora clock proteins or about the molecular foundations of circadian rhythms across fungi. Here, we examined 64 diverse fungal proteomes for homologs of all five Neurospora clock proteins and retraced their evolutionary history. The FRH and FWD-1 proteins were likely present in the fungal ancestor. WC-1 and WC-2 homologs are absent from the early diverging chytrids and Microsporidia but are present in all other major clades. In contrast to the deep origins of these four clock proteins FRQ homologs are taxonomically restricted within Sordariomycetes, Leotiomycetes and Dothideomycetes. The large number of FRH and FWD-1 homologs identified and their lack of concordance with the fungal species phylogeny indicate that they likely underwent multiple rounds of duplications and losses. In contrast, the FRQ, WC-1 and WC-2 proteins exhibit relatively few duplications and losses. A notable exception is the 10 FRQ-like proteins in Fusarium oxysporum, which resulted from nine duplication events. Our results suggest that the machinery required for FWO oscillator function is taxonomically restricted within Ascomycetes. Although the WC proteins are widely distributed, the functional diversity of the few non-Neurospora circadian oscillators suggests that a WC-FLO oscillator is unlikely to fully explain the observed rhythms. The contrast between the diversity of circadian oscillators and the conservation of most of their machinery is likely best explained by considering the centrality of noncircadian functions in which RNA helicase (FRH), F-box (FWD-1), WC-1 and WC-2 (light-sensing) proteins participate in fungi and eukaryotes. PMID- 20361496 TI - Disentangling the Collema-Leptogium complex through a molecular phylogenetic study of the Collemataceae (Peltigerales, lichen-forming Ascomycota). AB - Family Collemataceae (Peltigerales, Ascomycota) includes species of cyanolichens with foliose to fruticose or crustose thalli, with simple or septate ascospores. The current classification divides this family into two groups on the basis of ascospore types. The objective of this study was to evaluate the phylogenetic relationships within this family. Combined DNA sequence data from the nuclear large subunit and mitochondrial small subunit ribosomal RNA genes were used to evaluate monophyly of the family and the relationships between the largest genera of this family. The results revealed that this family is not monophyletic. Genera Staurolemma and Physma, currently classified within the Collemataceae, were found nested within the Pannariaceae. The second result of this study confirms that the genera Collema and Leptogium, both part of the Collemataceae s. str., are not monophyletic and that the presence of a thallus cortex is not a synapomorphy for Leptogium. The main taxonomic conclusion is that families Collemataceae and Pannariaceae were recircumscribed in light of molecular findings with the latter family now including Staurolemma and Physma. Genera Collema and Leptogium form a single mixed monophyletic group. Inferred ancestral character states within the Collema-Leptogium complex revealed that the ancestor of this family had a thallus without cortex and that a cortex evolved at least twice relatively early in the evolution of the Collemataceae s. str. These independent gains of a thallus cortex seems to be associated with a transition from colonizing bare rocks and soils in semi-arid and exposed habitats to epiphytism in shady humid forests. PMID- 20361497 TI - Phylogenetic study of Catapyrenium s. str. (Verrucariaceae, lichen-forming Ascomycota) and related genus Placidiopsis. AB - The current classification of what used to be called Catapyrenium comprises eight genera belonging to distinct lineages in the Verrucariaceae. Previous phylogenetic studies have shown that the redefined genus Catapyrenium (Catapyrenium s. str.) is monophyletic and sister of Placidiopsis within the Staurothele group, but this relationship was based on only two species from each genus. We conducted a phylogenetic study of Catapyrenium and Placidiopsis as currently delimited to evaluate the monophyly of each genus and infer infrageneric relationships. An initial family level phylogenetic analysis based on the nuLSU locus and implementing a backbone constraint tree (with both weighted maximum parsimony and bootstrap maximum likelihood approaches) was performed to infer phylogenetic placements of Catapyrenium and Placidiopsis taxa not included in previous molecular systematic studies. The results of this analysis were used to define the ingroup for a second phylogenetic analysis based on nuITS and nuLSU and centered on Catapyrenium s. str. and Placidiopsis. Placidiopsis was found to be monophyletic, whereas Catapyrenium s. str. was not. Catapyrenium dactylinum was found to be closely related to Placopyrenium caeruleopulvinum and Placopyrenium stanfordii, all of which were closely related to Placocarpus schaereri and Verrucula. In addition we found genus Placopyrenium to be polyphyletic. The resulting trees confirmed that Catapyrenium s. str. (excluding C. dactylinum) and Placidiopsis constitute two sister monophyletic entities. The data do not support Placidiopsis cinerascens and P. tenella as two distinct species because no characters can be used to distinguish them. Thus P. tenella is here reduced to synonymy with P. cinerascens. PMID- 20361498 TI - GDP-mannose transporter paralogues play distinct roles in polarized growth of Aspergillus nidulans. AB - GDP-mannose transporters (GMT) carry GDP-mannose nucleotide sugars from the cytosol across the Golgi apparatus membrane for use as substrates in protein glycosylation in plants, animals and fungi. Genomes of some fungal species, such as the yeast Saccharomyces cerevisiae, contain only one gene encoding a GMT, while others, including Aspergillus nidulans, contain two (gmtA and gmtB). We previously showed that cell wall integrity and normal hyphal morphogenesis in A. nidulans depend upon the function of GmtA and that GmtA localizes to a Golgi-like compartment. Cells bearing the calI11 mutation in gmtA also have reduced cell surface mannosylation. Here we show that GmtB colocalizes with GmtA, suggesting that the role of GmtB is similar to that of GmtA, although the respective transcript levels differ during spore germination and early development. Transcript levels of gmtB are high in ungerminated spores and remain so throughout the first 16 h of germination. In contrast, transcript levels of gmrtA are negligible in ungerminated spores but increase to levels comparable to those of gmtB during germination. These observations suggest that although GmtA and GmtB reside within the same subcellular compartments, they nevertheless perform distinct functions at different stages of development. PMID- 20361499 TI - Farnesol induces apoptosis and oxidative stress in the fungal pathogen Penicillium expansum. AB - This study was conducted to evaluate the effect of farnesol (FOH) on the growth of P. expansum. The viability of P. expansum cells was determined by counting the colony forming units (CFU) after each FOH treatment. Morphological changes of FOH treated fungal cells were analyzed by staining with Hoechst 33258, TUNEL (terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling), Annexin-V FITC and the oxidant-sensitive probe H2DCFDA (dichlorodihydro fluorescein diacetate). FOH strongly inhibited the growth of hyphae. The hyphal cells showed the hallmarks of apoptosis including chromatin condensation, DNA fragmentation, phosphatidylserine (PS) externalization, caspases activation, intracellular reactive oxygen species (ROS) generation but without nucleosomal ladder production. The abnormal cellular ultrastructure observed by transmission electron microscope (TEM) indicated that disintegration of cellular ultrastructure (especially for mitochondria) was linked to FOH-induced cell death. Taken together we demonstrated that FOH inhibits the growth of P. expansum and promotes apoptosis via activation of metacaspases, production of ROS and disintegration of cellular ultrastructure. PMID- 20361500 TI - Diversity of diatrypaceous fungi associated with grapevine canker diseases in California. AB - Eutypa lata is the most common diatrypaceous fungus in grapevine cankers. This study was undertaken to determine the presence and diversity of other members of the Diatrypaceae in grapevines in California. We isolated into pure culture 11 species of Diatrypaceae from the wood of diseased grapevines including Cryptosphaeria pullmanensis, Cryptovalsa ampelina, Diatrype oregonensis, D. stigma, D. whitmanensis, Diatrype sp., Diatrypella verrucaeformis and four putative species of Eutypella. Species were identified or grouped morphologically and by phylogenetic analyses of the complete sequence of the internal transcribed spacer (ITS) of the rDNA and beta-tubulin gene. Diatrypaceous fungi also occurred frequently on the native flora surrounding vineyards, thus serving as possible inoculum sources for these putative pathogens. PMID- 20361501 TI - Phylogenetic placement of plant pathogenic Sclerotium species among teleomorph genera. AB - Phylogenetic analyses and morphological characteristics were used to assess the taxonomic placement of eight plant-pathogenic Sclerotium species. Members of this genus produce only sclerotia and no fruiting bodies or spores, so Sclerotium species have been difficult to place taxonomically. Sequences of rDNA large subunit (LSU) and internal transcribed spacer (ITS) regions were determined for isolates of Sclerotium cepivorum, S. coffeicola, S. denigrans, S. hydrophilum, Ceratorhiza oryzae-sativae, S. perniciosum, S. rhizodes, S. rolfsii and S. rolfsii var. delphinii. Parsimony analysis grouped two species previously thought to be in the Basidiomycota, S. denigrans and S. perniciosum, within the Ascomycota; these species were found to have affinities with the teleomorph genera Sclerotinia and Stromatinia and the asexual Sclerotium cepivorum, which was known earlier to be related to Sclerotinia species. The other Sclerotium species were placed in one of two basidiomycetous groups, genera Athelia or Ceratobasidium. Based on rDNA analysis and morphology the basidiomycetous Sclerotium hydrophilum and S. rhizodes were transferred to genus Ceratorhiza, the anamorph of Ceratobasidium species. Sclerotium coffeicola was found to be close to S. rolfsii var. delphinii and S. rolfsii var. rolfsii, which was shown earlier to have an Athelia teleomorph. PMID- 20361502 TI - Diversity of trichomycetes in larval flies from aquatic habitats in Argentina. AB - Trichomycetes, mainly from nonbiting midge (Chironomidae), mosquito (Culicidae) and black fly (Simuliidae) larvae (Insecta: Diptera), are reported from diverse freshwater environments principally from previously unexplored areas of Argentina. Four new species of Harpellales are described: Austrosmittium patagonicum, A. lenticum, Smittium basiramosum and Legeriomyces lichtwardtii. This is the first report of Austrosmittium spp. from the Americas and the first report of a Legeriomyces from South America. Two other species (Simuliomyces sp. and Harpella sp.) are described but not named. Fourteen previously described species were recovered, and their geographical distribution and host ranges have been extended for Argentina, with Sm. phytotelmatum, Stachylina lentica, St. lotica and St. penetralis being new records for the country. PMID- 20361503 TI - First report of harpellales from the Dominican Republic (Hispaniola) and the insular effect on gut fungi. AB - We present the first report of Harpellales (Kickxellomycotina) from Hispaniola. The Dominican Republic was surveyed, and members of the ecological group trichomycetes were encountered in the gut of their arthropod hosts. Among Harpellales we describe a new species, Smittium caribense, and report the presence of seven previously known species that are new for Hispaniola: Genistellospora homothallica, Harpella amazonica, Harpella tica, Legerio-m myces rarus, Smittium culisetae, Smittium dipterorum and Stachylina grandispora. The dominance of cosmopolitan, dipteran-associated species is the most outstanding effect resulting from the insularity on gut fungi. PMID- 20361504 TI - Ulocladium cantlous sp. nov. isolated from northwestern China: its morphology and molecular phylogenetic position. AB - A new species of Ulocladium was isolated from diseased leaves from two Cucumis sp. growing in Sinkiang and Gansu provinces of China. Conidia were isolated from necrotic leaves and used to establish single-spore pure cultures. Conidia were harvested from cultures 7 d after incubation for morphological comparisons. The morphology of this species resembles that of U. botrytis and U. consortiale. However it is distinguished from these two species by the sizes of obovoid to broadly ellipsoidal conidia and longer conidiophores. A taxonomic description of U. cantlous, comparison with related species in this genus, and a species phylogeny based on the partial nucleotide sequence of the glyceraldehyde-3 phosphate dehydrogenase (gpd) gene and the Alternaria alternata major allergen (Alt a 1) gene are provided. PMID- 20361505 TI - Description of zygospores in Tectimyces robustus and clarifications on homothallic species within Harpellales. AB - Homothallic zygospores of the endosymbiont fungus Tectimyces robustus (Harpellales) are described (and the species is emended) confirming its position within genus Tectimyces, where it was placed originally based on characteristics of the asexual trichospores and thallus. Zygospores in T. robustus are similar to those reported in T. leptophlebiidarum, although fine morphological differences and ontogenic features of sexual spores clearly delineate both species. A morphological comparison of T. robustus zygospores with other homothallic species of Harpellales is provided. PMID- 20361506 TI - Taxonomy of Armillaria in the Patagonian forests of Argentina. AB - The taxonomy of Armillaria in southern South America has received little attention since the work of Singer and others. In this study we examine the morphological traits and cultural features for taxa representing the lineages revealed based on molecular phylogeny, and we link them to previously described taxa based on morphology. Lineages I-IV were identified as Armillaria novae zelandiae, A. montagnei, A. umbrinobrunnea comb. nov. and A. sparrei respectively. They could be differentiated morphologically based on dimension, features of the epicutis, annulus, stipe, hymenophoral trama and flavor and characteristics in culture. Furthermore there was no evidence of host preference for the species recognized. This is the first study integrating the phylogeny and morphology of Armillaria species from Patagonia, and it provides a foundation for future research on these fungi in South America. PMID- 20361507 TI - Hyperepiphyllous, perianthicolous hypocreales--highly specialized ascomycetes of the phyllosphere. AB - Five species of perithecial ascomycetes obligately infect the developing sporophytes of epiphyllous hepatics (Marchantiophyta, Porellales, Lejeuneaceae and Radulales, Radulaceae) while they are still enclosed by the calyptra and the perianth. These ascomycetes belong to the Hypocreales, which are especially well represented among the hyperepiphyllous fungi. The small and mostly brightly colored ascomata arise within the perianths and perforate its walls to discharge the ascospores. Conidiomata may be present as well. Colonization of the perianths prevents normal sporophyte development, sometimes causing deformities, while the foliose gametophyte remains unaltered. The fungus simultaneously can behave biotrophically toward the gametophyte and necrotrophically toward the sporophyte. Host fertility may be considerably reduced. Anthonectria mammispora is described as a new unispecific genus and Ticonectria testudinea as a new species. Ticonectria testudinea and presumably other species attack the region of the gametophyte-sporophyte junction including the transfer cells. The perianth inhabiting fungi occupy one of the most distinct and nutrient-rich microniches in bryophytes. They are sex- and organ-specific and seem to be restricted to certain hosts but are not poor in characters as are many bryophilous fungi. These species increase the complexity of the phyllosphere. PMID- 20361508 TI - Verrucostoma, a new genus in the bionectriaceae from the Bonin Islands, Japan. AB - Verrucostoma freycinetiae gen. et sp. nov. is described and illustrated from specimens on dead leaves of Freycinetia boninensis (Pandanaceae) collected in Hahajima, Bonin (Ogasawara) Islands, Japan. The genus is characterized by pale orange perithecia with protuberances around the perithecial apex, no color change in 3% potassium hydroxide and lactic acid, unitunicate asci, spinulose ascospores and an Acremonium-like anamorph. Morphological characters were compared with other genera in the Bionectriaceae and Nectriaceae (Hypocreales). Verrucostoma is morphologically similar to Bionectria (Bionectriaceae) from which it differs in the formation of conspicuous protuberances around the perithecial apex and the Acremonium-like anamorph. Moreover molecular analyses of Verrucostoma and other members of the Bionectriaceae and Nectriaceae based on alpha-actin, large subunit nuclear ribosomal DNA and RNA polymerase II subunit 1 sequences support the conclusions based on morphological data. Our results confirm that V. freycinetiae is distinct from other genera among the Nectria-like fungi and represents a new genus belonging to the Bionectriaceae. PMID- 20361509 TI - Diatrypasimilis australiensis, a novel xylarialean fungus from mangrove. AB - A marine xylarialean fungus, isolated from roots of Rhizophora (mangrove) in Australia, displays morphology of eight ellipsoidal dark brown ascospores in a cylindrical ascus having a refractive apical apparatus. Each ascospore has a longitudinal germ slit. The fungus grew very slowly and produced dark brown water soluble pigment(s) on various media. It developed unique, column-shaped, indeterminate synnemata on which needle-shaped conidia were produced. The sexual stage of this fungus was not observed under the laboratory conditions tested. Molecular phylogenetic analyses of the combined sequences of nuclear ribosomal RNA genes and their internal transcribed spacers placed it at a basal position in the clade of Diatrypaceae of the Xylariales with comparatively high statistical support. However the morphological features and phylogenetic position of this organism do not closely resemble any known fungal taxa. Therefore this fungus is proposed to be a representative of a novel taxon and described as Diatrypasimilis australiensis gen. et sp. nov. PMID- 20361510 TI - Suillus quiescens, a new species commonly found in the spore bank in California and Oregon. AB - Suillus quiescens sp. nov. is common under Pinus muricata on Santa Cruz and Santa Rosa Islands in the northern Channel Islands of California, and we subsequently found it fruiting at Point Reyes National Seashore on the central coast of California. Sequences from the internal transcribed spacer region show that it is distinct from all 44 species of Suillus tested, and features of its morphology separate it from all other unsequenced species. Suillus quiescens has a broader distribution than coastal California because it also was encountered as ectomycorrhizae on roots of pine seedlings from the eastern Sierra Nevada, coastal Oregon and the southern Cascade Mountains. The reason it had not been identified from these areas might be due to its resemblance to S. brevipes at maturity or it might be a rare fruiter that persists in the spore bank. PMID- 20361512 TI - Morchella anatolica (Ascomycota), a new species from southwestern Anatolia, Turkey. AB - Morchella anatolica (Ascomycota, Pezizales, Morchellaceae), a new species collected from pine forest of southwestern Anatolia, Turkey, is described and illustrated. PMID- 20361511 TI - Leucoagaricus decipiens and La. erythrophaeus, a new species pair in sect. Piloselli. AB - Leucoagaricus decipiens and La. erythrophaeus, are described as new from Sardinia, Italy, and California, USA, respectively. These sister species show distinct reddening when touched on all parts of the basidiocarps and darken on drying. Their collariate lamellae, broadly cylindrical to utriform cheilocystidia and trichodermal pileus covering distinguish them morphologically from other species in sect. Piloselli, while nrITS and EF1-alpha sequences distinguish them from each other. Leucoagaricus erythrophaeus has been known under the name Lepiota roseifolia, but the type collection of this species does not fit the interpretation. PMID- 20361513 TI - Luminescent Mycena: new and noteworthy species. AB - Seven species of Mycena are reported as luminescent, representing specimens collected in Belize, Brazil, Dominican Republic, Jamaica, Japan (Bonin Islands), Malaysia (Borneo) and Puerto Rico. Four of them represent new species (Mycena luxaeterna, M. luxarboricola, M. luxperpetua, M. silvaelucens) and three represent new reports of luminescence in previously described species (M. aff. abieticola, M. aspratilis, M. margarita). Mycena subepipterygia is synonymized with M. margarita, and M. chlorinosma is proposed as a possible synonym. Comprehensive descriptions, illustrations, photographs and comparisons with phenetically similar species are provided. A redescription of M. chlorophos, based on analyses of type specimens and recently collected topotypical material, is provided. The addition of these seven new or newly reported luminescent species of Mycena brings the total to 71 known bioluminescent species of fungi. PMID- 20361514 TI - Microwell enumeration of viable Saprolegniaceae in water samples. AB - Existing methods for enumeration of viable Saprolegniaceae propagules in water are laborious, time consuming and prevent examination of large numbers of samples or samples with high spore loads. In the present study a microwell plate (MWP) assay for estimation of Saprolegniaceae in water samples, modified from Hagen (1992), was evaluated. The ability of the assay to recover Saprolegniaceae was assessed by applying it to spore suspensions with four predetermined concentrations, 500-10,000 spores per liter of samples tested. The method also was used to analyze a set of field samples and compare it to a standard filtration method to ascertain its practicability. The MWP assay underestimated the number of spores in the test suspensions with predetermined concentrations. The accuracy of the assay varied with spore concentration, giving the lowest recovery (62.5%) at low spore numbers and the highest (86%) at intermediate concentrations (1000-5000 spores/L) for both isolates and growth media. The findings indicate that spores aggregate with increasing concentration. When applied to field samples the assay clearly distinguished among samples with presumptive differences in spore load and yielded significantly higher counts than the filtration method. The results justify the MWP method foruse in estimation of Saprolegniaceae in water bodies particularly relevant for monitoring of spore load in aquaculture as well as in ecological studies. PMID- 20361515 TI - William Clark Denison, 1928-2005. PMID- 20361516 TI - Assimilation of metal ions bound to porphyrins or porphyrin-peptides by vibrio vulnificus, a human pathogen inhabiting estuarine and marine environments. AB - Vibrio vulnificus, a ubiquitous microorganism in aquatic environments, causes serious septicemia to the immunocompromised host. In addition to protoheme, this species can utilize Fe-TCPP [ferric tetrakis (4-carboxyphenyl) porphine] as an iron source. In the present study, heme c bound covalently to the protein in cytochrome c, as well as the Fe-TCPP complex formed with a nanopeptide with a high affinity, was found to be useful iron sources for V. vulnificus. This bacterium was also revealed to use Zn-TCPP as a single zinc source. However, other metalloporphyrins such as Mn-TCPP and Pt-TCPP delayed the bacterial growth in the broth containing Fe-TCPP, suggesting interference in the iron assimilation. These results indicate that V. vulnificus may acquire metal ions from both free and peptide-bound metalloporphyrins. PMID- 20361517 TI - Bactericidal effect of HM-242, a novel disinfectant, against Pseudomonas aeruginosa. AB - The bactericidal effect of HM-242, a novel antimicrobial agent, against Pseudomonas aeruginosa was investigated by using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values and the time-kill study. Furthermore, we also morphologically investigated its effect against P. aeruginosa by use of transmission electron microscopy (TEM) in comparison with that of chlorhexidine digluconate (CHG). The bactericidal activity of HM-242 after 1 min incubation evaluated by MBC was 25 microg/mL, while the MBC of CHG was 50 microg/mL. In the time-kill study, the killing activity of HM-242 with 25 microg/mL incubation was stronger than that of CHG with 50 microg/mL incubation. MIC values of HM-242 and CHG against P. aeruginosa were 25 microg/mL and 12.5 microg/mL, respectively. We also observed via TEM the morphological changes in the test bacteria after being treated with each drug at 1/2MBC, 1MBC, 2MBC and 4MBC after 1 min or 5 min incubation. Under treatment with the same concentration of the test drugs, the cell damage with HM-242 treatment was greater than that with CHG. The appearance of empty cells was recognized at the concentrations greater than 50 microg/mL (2MBC) of HM-242 and 200 microg/mL of CHG (4MBC) after 1 min exposure, although no cell damage was evident below these concentrations. The cell-damaging effect against the test strain was dependent on the drug concentration and incubation time. The release of cell components and bleb formation were also recognized. These results suggest that HM-242 has more potent bactericidal activity in low concentrations under shorter time treatments than CHG. Both HM-242 and CHG act on the cell membrane and cell wall of P. aeruginosa and can destroy the cell integrity. We finally emphasize that HM-242 as well as CHG might be a suitable disinfectant for use in the medical field. PMID- 20361518 TI - Effect of bacterial media on the evaluation of the antibacterial activity of a biomaterial containing inorganic antibacterial reagents or antibiotics. AB - Several studies have been performed to assess the effectivesness of the antibacterial coating of a biomaterial to reduce surgical site infection. However, evaluations of these materials are inconsistent, and therefore it is difficult to compare their antibacterial performance. In this study, we evaluated the influence of different media such as nutrient broth (NB), Mueller-Hinton broth (MHB) and fetal bovine serum (FBS) on the antibacterial activity of AgNO3- or gentamicin-added bone cement using a modified ISO 22196 standard to devise a method to evaluate the antibacterial activity of biomaterials in vitro. The antibacterial activity results against Staphylococcus aureus and Escherichia coil were different in each medium. The antibacterial activity of AgNO3 in FBS was lower than the other media, whereas the antibacterial activity of gentamicin in FBS was higher than in the other media. It was assumed that the fluctuating antibacterial activity was influenced by serum components. The results showed that the ISO 22196 antibacterial evaluation method is suitable to evaluate antibacterial biomaterials after modifying the medium to FBS. PMID- 20361519 TI - Characterization of heterotrophic bacteria isolated from the biofilm of a kitchen sink. AB - Heterotrophic bacteria constituting the biofilm produced in a kitchen sink drain were analyzed, and the biofilm formation abilities and the hydrophobicity of the cell surface layer were measured for the isolates. When the biofilm sample was cultured at 36 degrees C and 25 degrees C for 7 days, there were about 10 times more colonies on oligotrophic R2A agar medium than on eutrophic BHI agar medium. From isolates from the biofilm sample, 13 bacterial species were detected. To examine the biofilm formation ability of these strains, we measured the absorbance (OD570) by crystal violet staining. The absorbance of Brevibacterium casei 7-R-36-1 was the highest (3.029). In the comparison of the absorbance values between genera, Brevibacterium spp. (4 strains) showed the highest absorbance (mean: 2.056), followed by K. pneumoniae (4 strains) with a mean of 1.111. Regarding the hydrophobicity of the isolates, the values ranged from 0.002 for P. nitroreducens (strain 1-B-36-2) to 0.096 for M. lacticum (strain 5-R-25 2). The hydrophobicity values were generally low, and the cell surface layer of all tested strains was highly hydrophilic. The diversity of species of bacteria in the biofilm sample produced in the kitchen sink drain was recognized, and all the isolates had biofilm formation abilities. PMID- 20361520 TI - Thermal death of Bacillus subtilis spores in oil-water systems. AB - The thermal death of the spores of Bacillus subtilis 168 in oil-water systems including emulsions and separated layers consisting of phosphate buffer and soybean oil or n-hexadecane was investigated. The resultant survivor curve consisted of two phases, an initial rapid reduction followed by a slow reduction, possibly as reflected by the death in the water phase and the oil phase, respectively. The concentration of oil in the system strikingly affected the pattern of thermal death. These results suggest that the spore location in the oil-water system may be a critical factor in determining the heat resistance. PMID- 20361521 TI - A new colored beverage disinfection system using UV-A light-emitting diodes. AB - In this study we evaluated the ability of the UV-A-LED to eliminate bacteria in a colored beverage. Ten edible pigments were used to make a colored solution at concentrations of 1.0%, 0.1%, 0.01% and 0.001%. We used a colony-forming assay to monitor the bactericidal action against the bacteria. The bactericidal effect of UV-A-LED against Escherichia coli DH5 a decreased with the increasing concentration of almost all of the edible pigments. Although less effective in colored solutions and commercially available orange juice than in the positive control PBS, it holds potential for further development and use to ensure food and water safety. PMID- 20361522 TI - Deaths: leading causes for 2005. AB - OBJECTIVES: This report presents final 2005 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the annual report of final mortality statistics. METHODS: Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2005. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. RESULT: In 2005, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Diabetes mellitus; Alzheimer's disease; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Septicemia. They accounted for about 77 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2005 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birthweight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Accidents (unintentional injuries); Respiratory distress of newborn; Bacterial sepsis of newborn; Neonatal hemorrhage; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. PMID- 20361523 TI - The modulation of reactive oxygen species production from human polymorphonuclear cells by curdlan derivatives as dectin-1 agonists/antagonists. AB - Reactive oxygen species (ROS) are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases including diabetes, neurodegenerative diseases, cancer and also influence central cellular processes such as proliferation, apoptosis, senescence etc. If in these pathological or degenerative conditions characterized by free radicals excess, reactive species are not eliminated, they can maintain destructive processes, already initiated at different cellular levels. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention. Toll-like receptors and C-type lectin receptor class V--Dectin-1, as members of Pattern Recognition Receptors play an essential role in innate immune response against bacteria and fungi respectively, contributing to pathogens recognition, phagocytosis, ROS production and induction of pro inflammatory cytokines secretion. Using a high performance chemiluminometric method, we studied the action of six Curdlan derivatives on the ROS production and release by activated human polymorphonuclear cells (PMNs) isolated from the peripheral blood of healthy donors. Our results demonstrated that Curdlan derivatives containing sulfopropyl groups did not activate human PMNs to release ROS. These compounds blocked Dectin-1 and were able to inhibit co-operation between Dectin-1 and TLR-2. Curdlan derivatives containing palmithoyl, carboxi methyl and sulfopropyl groups increased ROS release by human PMNs activated at TLR-2 level. Taking into account the fact that Dectin-1 can actively collaborate with TLR-2 to modulate the subsequent adaptive immune response, we can presume that Curdlan derivatives containing sulfopropyl group or palmithoyl/carboxi methyl/sulfopropyl groups, as possible Dectin-1 antagonists/agonists, could influence TLR-2 signaling. PMID- 20361524 TI - PI3K/Akt signaling in peripheral T lymphocytes from systemic lupus erythematosus patients. AB - PI3K/Akt/mTOR signaling pathway plays an important role in cellular proliferation and growth signaling. It was demonstrated that murine models presenting activated PI3K/Akt/mTOR signaling pathway in lymphocytes develop features of systemic autoimmunity, linking this pathway to autoimmune diseases. Therefore, the goal of our study was to analyze this signaling axis in Systemic Lupus Erythematosus (SLE), the prototype of systemic autoimmune diseases, focusing on Akt and p70S6k, two components of this pathway. Our results demonstrated that both expression and phosphorylation levels of Akt are more increased in SLE than in healthy donors (HDs) CD4+ T cells suggesting an up-regulation of PI3K and mTOR activities. This result was also suggested when p70S6k, one of mTOR substrate, was evaluated. Indeed, in SLE CD4+ T cells an enhancement of p70S6k activity, in direct correlation with its expression level, was found. Since p27kip1, an inhibitor of cell cycle progression, is one of the Akt substrates, we analyzed its expression level in relationship with cell cycle progression and apoptosis. The results demonstrated that p27kip1 expression level was significantly decreased in SLE than in HDs CD4+ T cells. In SLE p27kip1 level was inversely correlated with the percentage of peripheral lymphocytes in apoptosis and in S phase of the cell cycle. Therefore, the increased activity of PI3K/Akt/mTOR signaling pathway and, as a result, the drop of p27kip1 levels observed in CD4+ T cells isolated from SLE patients might explain the accumulation of SLE lymphocytes in S and G2/M cell cycle phases where they undergo apoptosis. PMID- 20361525 TI - Evaluation of the efficacy of a specific hyperimmune serum in experimental influenza infection in mice. AB - Serotherapy still remains a way of treatment in some diseases, and it could be consider superior to any other mode of action because the protecting substances of the body are the products of the organism itself. The aim of the study was to establish an "in vivo" method for testing the efficacy of therapeutic serum. Hyperimmune serum for influenza A/PR8/34 viral strain, was prepared in sheep, and tested for inhibition of haemagglutination and microneutralisation. Seroprotection was evaluated in mice one day after being challenged with a lethal dose of the same virus. Our study shows that protection occurred in all mice treated with undiluted hyperimmune serum one day post infection (no clinical signs, faster recovery of the body weight after the first three days of the infection, all mice survived). PMID- 20361526 TI - Genetic heterogeneity of group b streptococci isolated from Romanian pregnant women. AB - Although testing for group B streptococcus (GBS) carriage is mandatory during pregnancy, the laboratory data regarding the characteristics of GBS circulating strains among Romanian female population are scarce. This study aimed to evaluate the genetic diversity of 39 GBS isolates originating from the vaginal microbiota of pregnant women. All the isolates were susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, whereas 18% of them were resistant to either erythromycin or erythromycin and clindamycin. Serotyping based on capsular polysaccharide antigens revealed eleven isolates of type III (28%), seven of type II (18%), six of type la (15%), six of type Ib (15%), six of type IV (15%), and three of type V (8%), respectively. Pulsed-field gel electrophoresis (PFGE) of the Smal macrorestriction DNA fragments yielded 39 PFGE distinct profiles for the studied isolates. Computer-assisted cluster analysis of the band profiles, using unweighted-pair group method and Dice similarity coefficient, showed that at a minimum of 80% similarity, the GBS isolates gathered into 25 pulsotypes, irrespective of their serotype. Our results provided information about the genomic heterogeneity of GBS isolates circulating in our area, supporting the benefit of using PFGE as an adjunct to conventional typing methods for future epidemiological studies. PMID- 20361527 TI - Laboratory diagnosis of infectious diarrhoea syndrome; a three years study in two hospitals of infectious diseases. AB - Infectious diarrhoea is a syndrome caused by a variety of bacterial, viral and parasitic organisms which represents a major cause of morbidity and mortality all over the world. The wide diversity of etiological agents impairs the surveillance and the diagnosis and affects the correct treatment applied to reduce the long term complications. Besides well known enteric pathogens such as Salmonella, Shigella and Yersinia, a high number of emergent and re-emergent aetiologies are now recognised to be at the origin of diarrhoea. The lack of a correct diagnostic algorithm and adequate methods of analyses leads to under-evaluation and incertitude in an important number of clinical cases. Our study was designed as a complex analysis of the stool specimens collected from the patients, in the purpose to improve the laboratory diagnostic and to enhance the number of confirmed cases of infectious diarrhoea. A number of 756 samples from inpatients with diarrhoea were tested targeting pathogenic and opportunistic bacteria, viruses and parasites by classical and molecular methods. We documented that, in case of non-Salmonella, non-Shigella, non-Yersinia diarrhoea, the quality of diagnostic was improved by increasing the percentage of positive specimens to 22.49% compared to 11.12% when only bacteria, 5.56% when only viruses and 4.10% when only parasites were investigated. The laboratory data are of great value in evaluating the diarrhoea syndrome offering the documentation for an accurate epidemiological response and an adequate treatment. PMID- 20361528 TI - Aspergillus fumigatus meningitis in immunosuppressed patients; diagnosis, management, prevention and control. AB - Aspergillosis is a fungal disease that may be expressed by a diversity of clinical syndromes being produced by several of more than 170 Aspergillus species. The "Matei Bals" National Institute for Infectious Diseases has a long experience in diagnostic procedures and treatment of the immunosuppressed patients. Irrespective of the place of their residence, most patients with HIV infection and AIDS were investigated in the Institute in the last two decades. The first case of double central nervous infection (Mycobacterium tuberculosis and Aspergillus fumigatus) in a HIV positive patient is discussed. PMID- 20361529 TI - Pulsed-field gel electrophoresis associated to phage typing improves the discrimination of epidemiologically unrelated Salmonella enterica serovar typhimurium isolates. AB - A combination of phage typing and pulsed-field gel electrophoresis (PFGE) of Xbal and Blnl-digested chromosomal DNA has been used to study 18 epidemiologically unrelated human Salmonella enterica serovar Typhimurium isolates, which were collected during 2007 within a single Romanian county. Phage typing could assign only four of the isolates to three definitive phage types (DT41, DT86, and DT116), the rest being untypable by this classical method. PFGE analysis of the double enzyme-digested DNA, performed in an attempt to further discriminate the strains, allowed the typing of all the studied isolates. Xbal-digested genomic DNA segregated the isolates into 7 X-types and Blnl restriction differentiated them into 8 B-types. Our PFGE results documented the circulation of a rather homogeneous population of S. Typhimurium strains within the same county. As in the case of other human pathogens, epidemiological conclusions might be more accurate if based on both phenotypic and genotypic methods, therefore molecular typing should be added within the national laboratory-based surveillance of Salmonella infections. PMID- 20361530 TI - Susceptibility to antibiotics of Bacillus anthracis strains isolated in Romania. AB - A number of 21 B. anthracis strains isolated from 16 pustules, 2 blood cultures and 3 cerebrospinal fluids during 2000-2004 were studied for their susceptibility to antibiotics. The antibiosusceptibility testing was performed by disk diffusion method, on Mueller-Hinton agar medium. Two of the studied strains exhibited resistance to penicillins, considered until not long ago as antimicrobial agents of choice for the treatment of anthrax infection. The penicillin resistance explained the difficulties encountered during the treatment of these two cases as well as the fatal evolution in one of them. Both penicillin-resistant strains were subsequently tested, by using "in agar" antibiotic dilution method, in order to determine the minimum inhibitory concentrations (MIC) of the respective strains to penicillin G by the help of a serial antibiotic dilution from 16 microg/ml to 0.0075 microg/ml. The MIC values were 0.5 microg/ml and 4 microg/ml respectively, whereas in case of the standard B. anthracis 34F2 Sterne strain was < 0.015 microg/ml. All the 21 B. anthracis tested strains exhibited resistance to the IIIrd generation cephalosporins, as well as to TMP/STX, but were sensitive to tetracyclines and fluoroquinolones, these sensitivity aspects coming into agreement with the literature data. The strains proved to be also susceptible as follows: 13 strains to macrolides, 15 to rifampicin, 16 to chloramphenicol and all 21 to gentamycin; the last antibiotic can be used in association with fluoroquinolones in the treatment of B. anthracis infections. Fluoroquinolones (i.e. ciprofloxacin) become drugs of choice for the treatment of B. anthracis infections if early administered (within the first 24 hrs), in advance of the germ invasion into the lymph system and septicemia, preventing in this way the bacterial multiplication and production of edemathogenic and lethal toxins. PMID- 20361531 TI - Recognition and modulation of Dectin-1 and TLR-2 receptors by curdlan derivatives and purified natural extracts. AB - Toll-like receptors (TLRs) and Dectin-1, as members of Pattern Recognition Receptors play an essential role in innate immune response against bacteria and fungi respectively, contributing to pathogens recognition, phagocytosis, etc. Dectin-1 and TLR-2/TLR-6 can interact for intracellular signal transduction. Dectin-1 is expressed at low levels on macrophages and at high levels on dendritic cells. Dectin-1 and TLRs are synergistic in mediating cytokines production, such as IL-12 and tumor necrosis factor alpha (TNF alpha). In the present paper we studied the expression of Dectin-1 (beta-Glucan Receptor C-type lectin receptor class V) and TLR-2 on human normal monocytes cells and also the role of different Curdlan derivatives and highly purified natural extracts, especially their capacity to recognize these receptors and their Dectin-1 agonist/antagonist properties. Our results demonstrated that Curdlan derivatives containing sulfopropyl or palmythoil/carboximethyl/sulfopropyl groups and natural extracts could be potent immunomodulators with many potential applications (possible antagonists of Dectin-1, blockers of Dectin-1 cooperation with TLR-2). PMID- 20361532 TI - Serum markers in skin melanoma--preliminary study. AB - Skin melanoma presents the strongest metastatic capacity and the highest mortality rate of all types of skin cancer, being one of the most aggressive forms of human cancer. Although melanoma represents only 4% of skin cancers, it accounts for 80% of skin cancer deaths. The aim of this study was the investigation of two specific serum markers for melanoma: S100B and melanoma inhibitory activity in relation to disease development. The longitudinal study was performed on 51 patients diagnosed with skin melanoma and 72 healthy volunteers. For serum S100B and MIA measurement standard ELISA was used. The serum concentration of S100B was found significantly different from normal values only in patients in stage IV, in contrast to MIA, where significant differences occurred as early as stage II. The dynamics of the studied serum markers was in accordance with the skin melanoma evolution, especially for serum MIA. Only both increased S100B and MIA serum levels can indicate the disease evolution towards advanced stages and appearance of the metastatic processes. PMID- 20361533 TI - The effects of cold atmospheric plasma jets on B16 and COLO320 tumoral cells. AB - Cold atmospheric plasma treatment acts at the cellular level to remove diseased tissue without inflammation and damage, to suppress infections and to modulate the viability (apoptosis/necrosis) of tumoral cells. It is also known that, a major cause of anti-tumor chemotherapy failure is the development of multidrug resistance (MDR) of tumors. This study reveals the effect of high voltage pulsed, repetitive cold atmospheric plasma jets which are chemically activated with oxygen, on B16 tumoral cells (murine melanoma cell line) and COLO320DM multidrug resistant cells (human colon cancer cell line). The tests have been performed on human colon cancer cell line COLO320DM and murine melanoma cell line B16-F10. These cell lines have been treated with cold helium or helium-oxygen generated plasma jets and the consequent apoptosis has been analyzed by means of flow cytometric method. A treatment time-dependent apoptosis has been observed only in the case of 816-F10 cells interacting with helium-oxygen plasma and no apoptosis has been identified when the cells were treated only with helium plasma jets. These results indicate the need of oxygen for the chemical activation of plasma. The COLO320DM cells (that over-express the MDR efflux pumps) have been exposed to helium-oxygen plasmas only, or in a combination with vegetal extract MCS D161 as MDR efflux pumps inhibitor. For the secondly mentioned case the results have showed an increased apoptosis rate compared to the plasma treatment alone. The obtained data represent a starting point for the study of a possible combined treatment (atmospheric pressure cold plasmas and a MDR efflux pumps inhibitor applied with chemotherapy). PMID- 20361534 TI - Correlation between vaccine coverage against polio and circulation and genetic evolution of the poliovirus strains isolated in Romania in the framework of the global polio eradication strategy. AB - Until 2008 in Romania poliomyelitis has been controlled by predominantly using trivalent oral poliovirus vaccine (TOPV). The alternative vaccination schedule (formalin inactivated poliovirus vaccine IPV/OPV) has been implemented starting September 2008 and at the begining of 2009 was decided only vaccination with IPV. Between 1995-2006 the risk of the vaccine-associated paralytic poliomyelitis (VAPP) decreased with an average of less than 2 VAPP cases/year and no VAPP case between 2007 - September 2009. Begining with 2007 the number of the poliovirus strains isolated was less. All 9 poliovirus strains (PV) isolated between 2007 2009 and investigated by RT-PCR-RFLP in VP1-2A and VP3-VP1 coding regions showed Sabin-like profiles, and only one strain poliovirus type 3 showed Sabin 2-like profile by RFLP in 3D coding ARN polymerase region. The study about the seroprevalence of antibodies against poliovirus types in serum samples from the acute flaccid paralysis (AFP), facial paralysis (FP) cases showed that the seroprevalence of antibodies against types 1 and 2 Sabin strains was higher (>90%) than for type 3 Sabin strains (average 85%). It was confirmed the necessity of maintaining a proper vaccine coverage in population, after the switch in the vaccination strategy in Romania until all threats of poliovirus are eliminated globally. PMID- 20361536 TI - Phenotypic and genetic virulence and antibiotic resistance markers in Escherichia coli strains isolated from hospital surfaces. AB - The aim of this study was the phenotypic and genotypic analysis of the antibiotic resistance and virulence markers in enterobacterial strains isolated from the hospital environment. In this purpose, 100 enterobacterial strains isolated from hospital surfaces were investigated for their susceptibility patterns, for the ability to colonize the cellular (HeLa) and inert substrate and for the production of soluble, enzymatic factors. The bacterial strains were also investigated for the presence of resistance and virulence genes (aggR, aggA, EaggEC, EAST1, hlyA). The enterobacterial strains isolated from the hospital surfaces exhibited high levels resistance rates to beta-lactams, including 3'd generation cephalosporins, teteracyclines, sulphametoxazole and nalidixic acid. The PCR analysis demonstrated the presence of TEM1, tetA, tetB, tetC, dfrA12, sulI and sulII in a low percentage of the resistant strains. The majority of the tested strains exhibited ability to colonize the inert and cellular substrate and also the ability to produce a series of soluble enzymes implicated in enteric and extra-intestinal pathogenesis (pore forming enzymes, proteases, mucinases, iron chelating agents). The presence of beta-haemolysis on sheep blood agar was well correlated with the presence of hlyA gene, while the aggregative adherence pattern with the presence of aggA, aggR and EAST/1 genes, in different combinations. Our results are demonstrating that the E. coli strains isolated from the hospital environment harbor phenotypic and genetic virulence markers, thus contributing to the development of resistance and virulence genes reservoirs with potential implication for the human health in the hospital environment. PMID- 20361535 TI - Comparative methods for genotyping hepatitis C virus isolates from Romania. AB - Accurate genotyping of hepatitis C virus (HCV) has clinical implications for treatment orientation and epidemiological impact in tracing the contamination sources. The aim of the study was to compare a genotyping assay by restriction fragment length polymorphism (RFLP) in the HCV 5'untranslated region (5'UTR) with sequencing in the 5'untranslated and NS5B regions. One hundred and three samples, collected between 2004 and 2006 from chronically infected patients with HCV, were tested with the 5'UTR and NS5B protocols. Of the total number of the samples tested by the 5'UTR-RFLP assay (n=103) the HCV subtype could be inferred by this method for 92 samples, by 5'UTR sequencing for 16 samples out of 23 tested (n=23) and by using the NS5B sequencing for all the samples tested (n=34). Our results showed that the HCV genotype distribution in Romania is: 1b--86.4%, 1a--10.7% and 4a--2.9%. In conclusion, RFLP screening in the 5'UTR is a convenient method for HCV genotyping and discrimination between 1b and non-1b genotypes but has a poor resolving power for subtyping and evaluation of the transmission routes. Sequencing in NS5B region is more adapted than RFLP and sequencing in 5'UTR for subtyping and epidemiological investigation. PMID- 20361537 TI - Genetic characterization of Erwinia amylovora strains by random amplified polymorphic DNA fragments (RAPD). AB - Erwinia amylovora is the causative agent of fire blight, a destructive disease of rosaceous plants subjected to strict quarantine regulations worldwide. Previous studies showed that the population of E. amylovora in Romania is homogenous in its biochemical and serological characteristics, despite the different strains' geographical and host origin. The aim of the present study was to establish and test a typing method to quantify genetic diversity among the Romanian strains of this plant pathogen. Fourteen strains isolated from different hosts and geographical locations in Romania were examined by random amplified polymorphism DNA (RAPD) fragment analysis with two ten-base primers. This molecular method has not revealed any polymorphism, producing the same amplification patterns for all tested strains. Clustering of strains in the resulting dendrogram was not correlated with host, or region of isolation. The RAPD technique did not allow the detection of genetic markers in E. amylovora strains isolated in Romania and proved not to be discriminating among strains of this pathogen. The results presented in this study suggest that the population of E. amylovora in Romania is homogenous. PMID- 20361538 TI - The prevalence of some bacterial markers in female patients undergoing an initial infertility evaluation in north-east Romania. AB - SCOPE: Genital infections represent one of the most important causes of infertility, affecting: fallopian tubes, endometrial mucosa, sperm parameters. The aim of this study is to evaluate the involvement of four sexually transmitted infections (STD) in the achievement of infertility and to establish the prevalence of each infectious agent in our patients. METHODS: We analyzed the presence of Chlamydia trachomatis (CT) antigen, Ureaplasma urealyticum (UU), Mycoplasma hominis (MH) and Neisseria gonorrhoeae (NG) in the endocervical secretions and Chlamydia trachomatis antibodies IgA, IgG, IgM in the serum of 125 infertile women as well as in 30 pregnant women in the 3rd trimester of pregnancy, as a control group. RESULTS. In infertile women, the prevalence rate of the four bacterial markers was: CT antigen 1/125 (0.80%), CT IgG antibodies 19/125 (15.20%), MH 6/125 (4.80%), UU 51/125 (40.80%) and NG 1/125 (0.8%). From the control group, none was positive for CT antigen, but 1/30 (3.33% of patients) was positive for CT IgA while the prevalence rate for MH and UU were 16.66% and 43.33% respectively. CONCLUSIONS: We couldn't prove any association between genital MH/UU and infertility as the prevalence was higher in the control group than in the cases, but the correlation of the CT infection with the infertility was clearly shown. However, it is necessary to perform routine tests to screen for CT, NG, UU and MH among infertile patients. The positivity for CT IgG is a marker better correlated with fallopian tube obstruction than the CT antigen. PMID- 20361539 TI - The relationship between HPV16 and HPV18 viral load and cervical lesions progression. AB - Cervical cancer remains one of the most important mortality causes worldwide. It is already known that high risk HPV (HR-HPV) has the main role in the development of pre- or cancerous lesions. Despite the fact that many studies focused on the HR-HPV viral loads as possible biomarkers, the viral load quantification utility for all HR-HPV genotypes is still a controversy. The purpose of our study was to determine if HPV16 and 18 viral load values might be a potential marker for HPV infection clearance versus of pre- and cancerous lesions development. MATERIALS AND METHODS: 80 women who tested positive for HPV16 and 18 were selected from a cohort of 250 patients. The samples, consisting in cervical smears, were collected in transport media ESwab (Copan). The patient's average age was 36.26 years. HPV DNA detection, genotyping and viral load determination were performed twice for each patient (within one year follow-up). RESULTS: HPV 16 viral load was significantly higher in normal cytology samples and in HGSIL patients than in ASCUS/LGSIL (p value < 0.0312). HPV 18 viral load was also significantly higher in HGSIL cases than in ASCUS/LGSIL (p = 0,038). Independently of cervical cytology, HPV 18 viral load was lower (7.93 x 10(4) copies/microL) than HPV 16 viral load (5 x 10(13)) copies/microL). CONCLUSIONS: For HPV types 16 or 18 positive patients with LGSIL cytology the viral load might have predictive value. Our study suggested that patients with elevated viral loads are at disease risk progression and should be carefully evaluated. PMID- 20361540 TI - P16INK4A--A possible marker in HPV persistence screening. AB - The aim of this study was to investigate the correlation of p161NK4a expression levels with the cytological group of cervical carcinogenesis (NILM, ASCUS, LSIL, HSIL, cancer groups), in order to establish its value as potential diagnostic marker. METHODS: The smears obtained from 50 women with/without suggestive HPV infection pathology were subjected to cytological investigations. The viral testing was based on the detection of HPV DNA using the INNOLIPA kit, while the semiquantitative expression levels of p16INK4a were estimated by RT-PCR. RESULTS: p16INK4a expression level was correlated with the cytological degree of cervical lesions. In LSIL patients, p16INK4a values were 1.36 times greater than in NILM subjects (p = 0.07). In HSIL/cancer patients, p16INK4a values were 2.38 times greater than in NILM patients (p = 0.002). We also noticed significant differences between ASCUS: HSIL group (p = 0.02) and LSIL: HSIL (p = 0.07) group. The p16INK4a expression level was dependent of HPV genotype, p16INK4a mRNA presence being correlated with the presence of hrHPV in low and high risk lesions. PMID- 20361541 TI - Antidepressants work best for the severely depressed. PMID- 20361542 TI - Specialized support programs increase treatment adherence, reducing relapses for multiple sclerosis patients. PMID- 20361543 TI - Low-performing docs benefit most from P4P. PMID- 20361544 TI - DM grows, though under fire. PMID- 20361545 TI - Many states preparing laws rejecting individual mandate. PMID- 20361546 TI - HIEs are slow going but critical part of HIT. PMID- 20361547 TI - Small hospitals face heavy weather. PMID- 20361548 TI - Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation. AB - PURPOSE: The main objective of this study was to compare the opioid use patterns, resource utilization, and costs of patients on opioid therapy who have constipation with those who do not. DESIGN: Retrospective, observational matched cohort design METHODOLOGY: Patients initiating opioid therapy between Jan. 1, 1999 and Dec. 31, 2005 were identified from a longitudinal insurance claims database. Patients had > or = 30 days of opioid use and continuous plan coverage for > or = 6 months before and > or = 12 months after their index date, defined as the date of the first pharmacy claim for an opioid. Constipation was defined as having one or more ICD-9 codes of 564.0 during the follow-up period. Patterns of opioid use and resource utilization were compared between patients with constipation and a demographically matched (1:1) cohort of opioid initiators without consti- pation using t-tests and Chi-square (chi2) tests. PRINCIPAL FINDINGS: We identified 39,485 patients, of whom 2,519 (6.4%) had constipation. Most patients with constipation were female (66%) and > or = 45 years old (68%). Compared to controls, the constipation group had significantly higher rates of concurrent use of > or = 2 opioids (p < 0.0001), discontinuation, and switching between opioids. Patients with constipation had statistically significant higher hospital admissions, emergency room visits, home health services, nursing home care, physician office visits, other outpatient/ ancillary care, and laboratory tests. Patients with constipation had significantly higher mean all-cause costs for emergency, physician visits, nursing facility, home health, and prescription drug services compared to patients without constipation. CONCLUSION: Opioid treated patients with constipation were found to have significant differences in opioid use patterns and significantly higher health care utilization and associated costs. PMID- 20361549 TI - Doc shortage slows Medicare Advantage growth. PMID- 20361550 TI - Plans not mining data that could prevent falls. PMID- 20361551 TI - MelaFind improves chances for accurate melanoma diagnosis. PMID- 20361552 TI - Put DM in doctors' hands? PMID- 20361553 TI - Premium growth to reach 7.1% by 2015. PMID- 20361554 TI - [Carcinogenic effect of tobacco smoke]. AB - Both epidemiological and experimental studies provide evidence of the dose-effect relationship between the number of cigarettes smoked and lung cancer risk, exposure to tar or tobacco smoke and skin cancers or squamous cell carcinoma of the trachea and lung. Polycyclic aromatic hydrocarbons (PAHs) and volatile N nitrosamines, and also tobacco specific N-nitrosamines are considered to be the major carcinogens in tobacco smoke. To exert carcinogenic effect these compounds require previous metabolic activation by biotransformation enzymes. Individual susceptibility to chemical carcinogens is genotype and phenotype dependent. Machine-measured yields of tar, nicotine, carbon monoxide, benzo[a]pyrene and N nitrosonornicotine in cigarette smoke are significantly lower than actual intake by smokers. The following features have significant influence on the tobacco smoke composition, cancer risk and other disease risks relative to cigarette smoking: tobacco type and its modifications and also nitrate content in tobacco. Tobacco additives, including ammonia releasing substances, do not contribute to cigarette smoke composition and its toxicity. Filters, paper porosity, cigarette length and circumference as well as the number of tobacco cuts per inch (whether it is coarse-cut or fine-cut tobacco) are of primary significance for the chemical composition of cigarette smoke and health risk. PMID- 20361555 TI - [Role of the EFSA in risk management system regarding food contact materials and articles]. AB - The role of the European Food Safety Authority (EFSA) in the risk management system regarding food contact materials and articles is related with the risk assessment of the substances for the European Commission. General rules for the authorisation of substances used in materials and articles intended to contact with food is established in the Regulation (EC) no 1935/2004. For the evaluation of substances their toxicological properties and magnitude of migration into food simulants is taken into account. Toxicological studies include the mutagenicity tests, oral toxicity studies, carcinogenicity, reproduction and also studies on absorption, distribution, metabolism and excretion of the substance and other studies when needed. The set of the relevant toxicological data for substance depends on the magnitude of migration. In the case of positive opinion by EFSA the substance appears on the Community list of authorised substances. Sometimes, the earlier evaluated and authorized substances must undergo re-evaluation due to their new toxicological properties or as a result of a presence in the food of their earlier unknown decomposition products. Examples of the selected substances which underwent re-evaluation by EFSA in the light of the current toxicological knowledge and the relevant activities undertaken by the European Commission have been presented. PMID- 20361556 TI - The effects of di-n-butyl phthalate on the germ cells of laboratory mice. AB - Phthalate are found in the environmental samples due to their wide use in the industry as plasticizers. Di-n-butylphthalate (DBP) is mainly used in nitrocellulose and polyvinyl acetate products as well as in personal-care products. This study was performed to investigate the influence of exposure to DBP on the quantity and quality (motility, morphology) and DNA damage (induction of micronuclei and DNA strand breaks) of male mice gametes. The estimation of DBP residues was also done. Eight weeks exposure to DBP (500 mg/kg bw and 2000 mg/kg bw) did not significantly affect testes and epididymes weights as well as sperm count. DBP clearly diminished sperm motility, enhanced frequency of abnormal sperm heads and not significantly increased DNA strand breaks in germ cells as well as frequency of micronuclei in spermatids. There were no bioacumulation of DBP in mice. Results suggest that DBP may affect the male mice germ cells. PMID- 20361557 TI - [Determination of malachite green and leukomalachite green residues in fish muscle by high-performance liquid chromatography method]. AB - Malachite green (MG) and leukomalachite green (LMG) are subjected to monitoring fish muscle, with a minimum required performance limit (MRPL) set 2 microg/kg. Samples were extracted with acetonitryle-buffer mixture and cleaned up on SCX solid phase extraction (SPE) column. LC separation MG and LMG was done on column Luna Phenyl-Hexyl Phenomenex. Samples were fortified with MG and LMG between 2 - 25 microg/kg. The coefficients of variation (CV%) were lower than 14% for MG and 16%for LMG. The mean recoveries were in the range 65- 83% for MG and 70- 73% for LMG. This method fulfils the criteria for identification and determination of MG andLMG residues in the samples of fish muscle. PMID- 20361558 TI - [Determination of boron content in natural mineral and spring waters by ICP-OES technique]. AB - Maximum admissible level of boron concentration in water intended for human consumption and in natural mineral and spring waters is usually estimated taking into account actual WHO criteria and requirements listed in Directive No 98/83/EC - 1 mg/l. In majority countries of European Union maximum admissible level of boron in water intended for human consumption is 1 mg/l, however in Slovakia and in Netherlands maximum admissible levels of this element are 0.3 mg/l and 0.5 mg/l, respectively. In this work developed and validated method of determination of boron by inductively coupled plasma emission spectrometry technique was applied for determination of this element in 26 natural mineral and spring waters. Concentrations of boron determined in sixteen mineral and spring waters analyzed were in the range from 0.029 mg/l to 0.552 mg/l while in ten waters analyzed the contents of boron were below 0.026 mg/l. The contents of boron in analyzed waters were below maximum admissible level in Poland presented in the Decree of Minister of Health from 29 March 2007 on the quality of water intended for human consumption and were not dangerous for human health. PMID- 20361559 TI - [The content of phenolic acids in the edible parts of selected varieties of apples]. AB - Fruits and vegetables are essential sources of many nutritive substances which are necessary for normal function of the organism. One of the mostly consumed fruits in many European countries, including Poland is apples. The prohealthy properties of apples are associated with the contents of polyphenolic compounds, thus including in parts phenolic acids which have antioxidant properties. The concentration of these compounds depends on many factors such as variety climate and soil conditions, maturity as well as agro technical operations. The aim of this investigation was to compare the concentrations of phenolic acids and epicatechin in the varieties of apple Champion and Jonica, which were collected from different orchards around Lublin. The phenolic compounds were assayed using a Symmetry column carrier RP-C18 (Waters) integrated with a high pressure liquid chromatography apparatus. The dominant phenolic acids found in the Champion variety was chlorogenic acid, whereas in the Jonica variety, chlorogenic and homovanilic acids were the dominate once. The highest concentrations of chlorogenic acid was detected in the pulp of an apple (Jonica variety) collected from the orchards around the cities of Pulawy and Lublin, whereas homovanilic acid was the highest in the other samples collected from the orchards in the vicinity of Stryjno and Gory Markuszowskie. Among the Jonica and Champion varieties of apples collected from various orchards in the vicinity of Lublin, the highest content of epicatechin (13,12 mg/kg) was found in the pulps of Champions variety collected in Pulawy. In general, the Champion variety was the best source of phenolic acids and epicatechin compared to the Jonica variety independent of the harvest zone. PMID- 20361560 TI - [Changes in the content of total sugars present in potato tubers depending on the agrotechnical treatments]. AB - The aim of this paper was determination of the effect of the soil tillage systems (traditional and simplified) and weed control methods for herbicides (Plateen 41,5 WG, Plateen 41,5 WG + Fusilade Forte 150 EC, Plateen 41,5 WG + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC, Barox 460 SL, Barox 460 SL + Fusilade Forte 150 EC, Barox 460 SL + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC) on the content of total sugars in the edible potato tubers cv. Wiking. The statistical analysis revealed a significant effect of the soil tillage and weather conditions over the experimental years on the content total sugars. The simplified used in the tillage soil increased the content sugars, as compared with the traditional tillage. During hot and dry vegetation weather the potato tubers accumulated the least total sugars. It was stated that the content of total sugars decreased after preliminary processing (after peeling) as compared to level of sugars non-peeled potato tubers. PMID- 20361561 TI - [Can health behavior of Polish adolescents foster prevalence of overweight and obesity?]. AB - The aim of this study was to assess the prevalence of overweight and obesity and health behavior leading to those diseases among Polish adolescents. In year 2006 a survey study was conveyed among a representative sample of 530 girls and 518 boys aged 11-16 from whole territory of Poland. Overweight and obesity were noted in 8.7% of girls and 10.2% of boys. Among studied subjects a low level of physical activity (60% of boys and 70% of girls did not reach the recommended level of physical activity) and large amount of time spend in front of TV and computer (4 hours during the weekdays and 5.5 hours during days off school) were observed. Study also showed negative dietary habits: skipping first breakfasts and eating too many sweets and sweetened soda beverages and salted snacks as well a tendency to buy unhealthy products at school shops. PMID- 20361562 TI - [Elementary schoolchildren nutritional behaviors in pupils' and their parents' opinion]. AB - The aim of this study was to compare pupils' and their parents' opinions of children nutrition behaviors. There were 97 pupils at the age of 10 and 87 parents participating in the study. Data was collected using questionnaire, filled by pupils and parents separately, including questions about: number and frequency of meals a day, frequency of fast food consumption and providing buying food in school shops. It was noted that parents' knowledge about children's nutrition behaviors was inadequate in comparison to pupils' declarations. School environment becomes important place to form health behaviors. It seems necessary to change nutrition policy in Polish schools by: changing of methods and teaching ranges of rational nutrition, improving school meals organization, changing assortment of food in school shops and regular education of people who are responsible for children nutrition behaviors. PMID- 20361563 TI - [Assessment of vitamins and minerals intake with supplements during breast feeding]. AB - Assessment of supplements intake during breast-feeding was aim of the work. Seventy three women were examined in age 19-42 years coming from the Lublin province. The information about applying supplements during breast-feeding was obtained using questionnaire method. Achieved results served for calculations of taking vitamins and minerals coming from supplements. During breast-feeding 48% women accepted supplements. Average intakes of vitamin B2 (113%), B6 (120%), folic acid (144%) and vitamin D (166%) from supplements were above 100% recommended values. The highest average consumption was noted for iron (229% of recommended value), however the lowest on level 10-35% recommendations for vitamin A (33%), calcium (11%), selenium (12%) and magnesium (20%). Nearly 100% of the norm realization was obtained in case of the vitamin C (93%), E (102%), PP (105%), B1 (107%) and zinc (99%). PMID- 20361564 TI - [Nutritional supplementation in children and adolescents practicing fencing]. AB - The aim of this study was to assess the use of nutritional supplementation during the days of training and the days free of training in children and adolescents who attend sports schools, Questionnaires on the use of nutritional supplementation were filled in by 141 children and adolescents who practice fencing. The factor gender-age had statistically significant impact only on using mineral supplementation by the studied students. Using ergogenic aids as well as using vitamin and mineral supplements or other kind of supplementation was rare in the studied population, but was more frequent during the days of training. Nutritional supplementation was always used by higher percentage of boys than girls. PMID- 20361565 TI - [Evaluation of the effect of diet composition and its supplementation with selected B vitamins on distribution of calcium and magnesium in the body]. AB - The aim of the study was to estimate, on an animal model, the influence of diet composition and its supplementation with selected B vitamins on distribution of calcium and magnesium in the body. The change in diet composition was found to significantly reduce the calcium contents in the liver and blood of males as well as in the liver and kidney of females. The change enhanced calcium and magnesium accumulation in the skeletal muscles of the animals examined. In females, the effect was augmented by supplementation. The vitamin supplementation applied was conducive to incorporation into the bones calcium in males and magnesium in females, respectively. Analysis of the results allows to conclude that both the change in the diet composition and the supplementation of the diet modified by selected B vitamins significantly affected distribution of calcium and magnesium between different organs and tissues of the animals examined and probably modified the functional status of the organs and tissues in question. The magnitude and direction of the changes in most parameters analysed were sex dependent. PMID- 20361566 TI - [The influence of probiotic supplementation on girls' red blood cell characteristics]. AB - Probiotics are characterized by comparatively great metabolic activity not only immodulation one, but also when synthesizing some group B vitamin, polyamines and arginine in alimentary canal. These are the factors stimulating erythropoiesis and haemopoiesis. The aim of this work was to investigate the probiotic influence on the red blood cell behavior of 18-19 year-old girls accommodated and fed in boarding school. The group being tested received the probiotic preparations Trilac and Blonnik (Fibre) three times a day for 6 weeks. Initially and after 6 week feed the red blood cell indices were quantified None of the essential statistic alterations of these indices have been discovered after this 6 week probiotic supplementation in comparison to output values. The haematologic characteristics tested stayed within the limits. It is not out of the question that the length of feeding was too short. PMID- 20361567 TI - [Quantitative assessment of daily food rations of obese persons]. AB - The aim of the study was to assess the energetic and nutritional values of diets in obese subjects (BMT > or = 30 kg/m2). A total of 261 patients of the Obesity Treatment Centre (201 women - BMI = 32.9 +/- 6.2 kg/m2 and 60 men-BMI = 33.4 +/- 5.3 kg/m2) were enrolled in the study. The mean age of women was 45.8 +/- 12.2 years, men 48.8 +/- 13.5 years. Daily food rations were performed using the 24h dietary recall referring to the day preceding the examination. Although the rations were shown to have a satisfactory energetic value they were improperly balanced with respect to protein and fat. Food rations of the study patients were characterized by excessive intake of animal protein, total fat, saturated fatty acids and dietary cholesterol, especially in men. Insufficient intakes of vegetable protein, total carbohydrates and dietary fibre were noted in the study patients of both sexes. PMID- 20361568 TI - [Estimation of the level of nourishing ingredients intake in a group of young women doing fitness as recreation]. AB - The research was conducted into 120 women aged 19-25 years old who take up regular physical activity in fitness clubs. The quantity analyse of daily food rations was conducted on the base of food interview about consumption within 72 hours preceding the research. Energetic value and basic nourishing ingredient supply was estimated, supply of selected vitamins dissolved in fats (A, E) and in water (C, B1, B2, PP) and also the average content of mineral ingredients (Na, K, Ca, Mg, Fe). The established average supply of nourishing ingredients was compared to the dietary standards regarding women aged 19-25 years old of moderate physical activity. The results of the conducted research indicate lack of balanced content of nourishing ingredients in daily food rations of the tested women. Energy supply was far too low comparing to recommended standards. It was proved that carbohydrate and fat supply was definitely lower than recommended standards (suitably: 209.7 g/daily and 28.1 g/daily), protein content exceeded the level of safe consumption by 11.3%. The research also showed low consumption of cholesterol (105.7 mg/ daily) and dietary fibre (18.8 mg/daily). Furthermore, shortage of vitamins A, E, B2 and mineral ingredients (K, Ca, Fe) was also proved. Higher than recommended supply of vitamin C, PP, sodium and magnesium was found. Less than half of the tested women followed supplementary diet of mineral and vitamin preparations. PMID- 20361569 TI - [Assessment of selected vitamins content in daily food rations of obese patients]. AB - The study objective was to evaluate the content of chosen vitamins soluble in fats (A, E) and in water (B1, B2 B6, B12, C, niacin, folic acid) in daily food rations of obese subjects, who are not on a reducing diet (201 obese women - BMI = 32.9 +/- 6.2 kg/ m2 and 60 men - BMI = 33.4 +/- 5.3 kg/m2). The mean age was 45.8 +/- 12.2 years for women and 48 +/- 13.5 years for men. Dietary habits were assessed using the 24 h dietary recall method. Computer program DIETA2 was used to evaluate the vitamin content in daily food rations. Vitamin intake was compared with safe levels for subjects with low physical activity. Low intake were observed in the consumption of vitamin B1 in women and B2 in men. Daily food rations of patients with excessive body mass (both women and men) met safe level daily requirements for vitamin E, niacin, folic acid, riboflavin (women), vitamin B6 (men). High intakes of vitamin A, B12, and C were noted both among obese women and men. PMID- 20361570 TI - [Nutritional habits in children and adolescents practicing fencing. Part 1. Meal consumption]. AB - The aim of this study was to assess habits related to eating meals in children and adolescents who attended sports schools. The days with training and the days free of training were analysed separately. The questionnaires on the number and frequency of eating meals were filled in by 141 children and adolescents who practised fencing and attended sports classes in primary and secondary schools. The influence of gender and age on the number and frequency of eating meals was analysed by means of the SPSS 12.0 PL for Windows computer programme. The studied children's and adolescents' habits related to eating meals were highly unfavourable, especially in females from secondary school, mainly due to a very low percentage of students who ate meals regularly, lunch in particular. Boys ate more meals than girls. Especially disconcerting was a very low number of meals eaten by females from secondary school, which may imply a risk of anorexia. Children and adolescents who attend sports schools should be educated on nutrition and the relation between food habits, nutritional status and achieving success in sport. Females from secondary schools should be informed about the danger of anorexia. PMID- 20361572 TI - Oral health risks of tobacco use and effects of cessation. AB - The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages. PMID- 20361571 TI - Consensus Report: 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals. AB - Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis. PMID- 20361573 TI - Public health aspects of tobacco control revisited. AB - The tobacco epidemic presents a major public health challenge, globally, and within Europe. The aim of the Public Health Work Stream at the 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals was to review the public health aspects of tobacco control and make recommendations for action. The paper reports on the size of the tobacco challenge; from the associated mortality and morbidity to the prevalence of exposure to, and use of, tobacco. It provides a review of progress on tobacco control measures, as monitored by the World Health Organisation, and the impact of multiple influences on tobacco use. Every member of the dental team was considered to have a role as a public health advocate in promoting health and preventing disease in order to address health inequalities. A range of evidence based approaches to tobacco control from clinical practice through to public policy are advocated, using the principles of the Ottawa Charter, recognising the multiple determinants of health. Tackling the tobacco epidemic may require a paradigm shift in oral healthcare. Therefore, key resources for health professionals on tobacco control are discussed and the implications of the findings for research, policy and practice in Europe are explored. PMID- 20361574 TI - Improving the effectiveness of tobacco use cessation (TUC). AB - This paper includes an update of a Cochrane systematic review on tobacco use cessation (TUC) in dental settings as well as narrative reviews of possible approaches to TUC and a more detailed discussion of referral for specialist TUC services. On the basis of these reviews we conclude that interventions for tobacco users in the dental setting increase the odds of quitting tobacco. However, the evidence is derived largely from patients using smokeless tobacco. Pharmacotherapy (such as nicotine replacements, bupropion and varenicline) is recommended for TUC in medical settings but has received little assessment in dental applications, although such evidence to date is promising. Whether the dental setting or referral to specialist TUC services is the most effective strategy to help people to quit tobacco use is unclear. An effective specialist service providing best available TUC care alone may not be the answer. Clearly, such services should be both accessible and convenient for tobacco users. Closer integration of specialist services with referrers would also be advantageous in order to guide and support oral health professionals make their referral and to maximise follow-up of referred tobacco users. Future research direction may consider investigating the most effective components of TUC in the dental settings and community-based trials should be a priority. Pharmacotherapy, particularly nicotine replacement therapy, should be more widely examined in dental settings. We also recommend that various models of referral to external and competent in-house TUC specialist services should be examined with both experimental and qualitative approaches. In addition to overall success of TUC, important research questions include facilitators and barriers to TUC in dental settings, preferences for specialist referral, and experiences of tobacco users attempting to quit, with dental professionals or specialist services, respectively. PMID- 20361575 TI - Education of tobacco use prevention and cessation for dental professionals--a paradigm shift. AB - The use of tobacco continues to be a substantial risk factor in the development and progression of oral cancer, periodontitis, implant failure and poor wound healing. Dental and dental hygiene education providers have made great advances towards the incorporation of tobacco education into their curricula in recent years. Unfortunately, however, both medical and dental education research has consistently reported schools providing only basic knowledge-based curricula that rarely incorporate more effective, behaviourally-based components affecting long term change. The limited training of oral healthcare students, at least in part, is reflected in practising dental professionals continuing to report offering incomplete tobacco interventions. In order to prepare the next generation of oral healthcare providers, this paper proposes a paradigm shift in how tobacco use prevention and cessation (TUPAC) may be incorporated into existing curricula. It is suggested that schools should carefully consider: to what level of competency should TUPAC be trained in dental and dental hygiene schools; the importance of establishing rapport through good communication skills; the core knowledge level for TUPAC; suggested instructional and assessment strategies; the importance of continuing professional education for the enhancement of TUPAC. PMID- 20361576 TI - Role and models for compensation of tobacco use prevention and cessation by oral health professionals. AB - Appropriate compensation of tobacco use prevention and cessation (TUPAC) would give oral health professionals better incentives to provide TUPAC, which is considered part of their professional and ethical responsibility and improves quality of care. Barriers for compensation are that tobacco addiction is not recognised as a chronic disease but rather as a behavioural disorder or merely as a risk factor for other diseases. TUPAC-related compensation should be available to oral health professionals, be in appropriate relation to other dental therapeutic interventions and should not be funded from existing oral health care budgets alone. We recommend modifying existing treatment and billing codes or creating new codes for TUPAC. Furthermore, we suggest a four-staged model for TUPAC compensation. Stages 1 and 2 are basic care, stage 3 is intermediate care and stage 4 is advanced care. Proceeding from stage 1 to other stages may happen immediately or over many years. Stage 1: Identification and documentation of tobacco use is part of each patient's medical history and included into oral examination with no extra compensation. Stage 2: Brief intervention consists of a motivational interview and providing information about existing support. This stage should be coded/reimbursed as a short preventive intervention similar to other advice for oral care. Stage 3: Intermediate care consists of a motivational interview, assessment of tobacco dependency, informing about possible support and pharmacotherapy, if appropriate. This stage should be coded as preventive intervention similar to an oral hygiene instruction. Stage 4: Advanced care. Treatment codes should be created for advanced interventions by oral health professionals with adequate qualification. Interventions should follow established guidelines and use the most cost-effective approaches. PMID- 20361577 TI - Access to dental care in Tennessee. PMID- 20361578 TI - Emergency dental services for indigent adults. PMID- 20361579 TI - Tennessee's Federally Qualified Health Centers: improving access to oral health care. PMID- 20361580 TI - "No Child Overlooked" an access to care success story. PMID- 20361581 TI - Tennessee's public dental care programs. PMID- 20361582 TI - Expanded duties and dental assistant education. PMID- 20361583 TI - Tennessee's faith-based clinics: a vital piece of the puzzle. PMID- 20361584 TI - Department of Health Oral Health Services in Tennessee. PMID- 20361585 TI - The Dental Angel Fund Foundation: one solution for access to adult emergency dental care in Tennessee. PMID- 20361586 TI - Head Start Dental Home initiative addresses access to care. PMID- 20361587 TI - Remote Area Medical. PMID- 20361588 TI - Donated Dental Services helps vulnerable Tennesseans: childhood hero inspires Madisonville dentist to give back. PMID- 20361589 TI - Dental education and access to care. PMID- 20361590 TI - [Establishment of a method for rapid detection of the nucleic acid of the novel A (H1N1) influenza virus]. AB - A new flu caused by a novel influenza A(H1N1) virus has spread over the United States, Mexico and more than 40 other countries. And because of the immediate global concern, WHO has announced that the current level of influenza pandemic alert is raised to phase 5, indicating approaching of an influenza pandemic. As patients suffering from the influenza A (H1N1) have the similar symptoms as patients with seasonal influenza, differential detection and identification of the influenza virus have to depend on specific laboratory tests. We have successfully developed a RT-PCR based method for detection of the influenza A (H1N1) virus, and had applied the method to detection of clinical samples. PMID- 20361591 TI - [Laboratory confirmation of the first influenza A (H1N1) imported case in Mainland China]. AB - The clinical throat swab specimen of an imported suspected case of influenza A (H1N1) was detec ted with real-time PCR, RT-PCR and subsequently confirmed by gene sequencing. The presence of influ enza A (H1N1) virus confirmed the first case with A (H1N1) infection in Mainland China. PMID- 20361592 TI - [Review on the etiological property of 1918/1919 Spainsh flu virus (H1N1)]. PMID- 20361593 TI - [Review on the etiological property of 1957 Asian flu virus (H2N2)]. PMID- 20361595 TI - [Review on the etiological property of 1977 Russian flu virus (H1N1)]. PMID- 20361594 TI - [Review on the etiological property of 1968 Hong Kong flu virus (H3N2)]. PMID- 20361596 TI - [Epidemiology of 1918 flu]. PMID- 20361597 TI - [Epidemiology of 1957 flu]. PMID- 20361598 TI - [Epidemiology of 1968 flu]. PMID- 20361599 TI - [Epidemiology of 1977 Russian flu]. PMID- 20361600 TI - [Review on the etiological property of the swine influenza virus]. PMID- 20361601 TI - [Organization of occupational therapeutic service, dynamics and structure of occupational morbidity in Krasnoyarsk area]. AB - The authors present organizational and functional structure of occupational therapeutic service in Krasnoyarsk area, major functional divisions of the territorial occupational therapeutic center and their activities. The article covers analysis of changes in levels and structure of occupational morbidity, defines main ways to optimize occupational therapeutic service for the territorial workers. PMID- 20361602 TI - [Trends and dynamics of occupational morbidity (according to materials of Samara region)]. AB - The article presents data on occupational morbidity in Samara region over 1980 2008. Increased values are noted, that is due to improved efficiency of occupational therapeutic service, according to the authors. PMID- 20361603 TI - [Topical problems of occupational allergic diseases nowadays]. AB - The article covers materials on occupational allergic diseases prevalence in variable economic branches of Baikal area, if compared to the values in Russian Federation in general. The authors defined major etiologic factors resulting in allergic diseases, demonstrated that immune suppression is a major concept in occupational skin and respiratory system diseases, revealed immune response peculiarities in accordance with acting occupational allergen type. PMID- 20361604 TI - [Neuropsychologic traits in individuals with chronic exposure to mercury at work]. AB - The article deals with diagnostic peculiarities of neuropsychologic traits in individuals with previous exposure to industrial neurotoxic chemicals. Pilot studies demonstrated brain disorders characteristic for toxic (mercurial) and vascular (discirculatory) encephalopathies, justified necessity of neuropsychologic approach in occupational therapeutic diagnosis. The authors presented results of suggested scheme of neuropsychologic prompt screening aimed to reveal higher psychic functional disorders in individuals with occupational neurointoxications. PMID- 20361605 TI - [Computer visual syndrome and occupational ophthalmopathy in PC operators]. AB - Information technologies development resulted in occupational ophthalmopathy in PC users. The article covers criteria to define the risk group for prevention and rehabilitation measures. PMID- 20361606 TI - [Registers of health for workers exposed to extremely dangerous toxic chemicals- basis for early diagnosis and prevention of occupational intoxications]. AB - The article deals with results of specification and functioning of a register of health for workers exposed to extremely dangerous toxic chemicals. The authors demonstrated patterns of diseases development in workers according to length of work with toxic chemicals and to work conditions. The identified cause-effect relationships of the diseases development necessitate health registers to minimize negative consequences in work conditions, for early diagnosis and occupational diseases prevention. PMID- 20361607 TI - [Experimental steroid osteoporosis in rats and the way to restore the bone tissue structure]. AB - Experimental prednisolone administration has been shown to cause osteoporosis in animals. A single administration of fetal tissue--10-day fetal homogeneous tissue at a dose of 0.5 mg into the experimental animal femur improves the bone tissue structure, hastens its remodeling, contributes to elimination of the bone tissue pathologic process in osteoporosis. PMID- 20361608 TI - [Somatostatin receptors and its analogs in diagnosis and treatment of human tumors]. PMID- 20361609 TI - [Five- and ten-year actual and relative survival of colon cancer patients (C18) (Population Cancer Register Database, St. Petersburg)]. PMID- 20361610 TI - [Effectiveness of gefitinib (Iressa) as first-line therapy for inoperable non small-cell lung cancer with mutated EGFR gene (phase II study)]. AB - Tumor regression was reported in 20-30% of patients with inoperable non-small cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC. PMID- 20361611 TI - [Outcomes of surgical treatment for locally advanced gastric cancer]. AB - Results of surgical treatment of 223 patients with locally advanced gastric cancer (2000-2005) are presented. Postoperative complications rate was 25.6 +/- 2.5%, mortality--5.8 +/- 0.7%, overall survival--17.9 +/- 2.6%, median survival- 12 months. Survival rates were higher following palliative treatment. Groups of patients in which RO resections failed to improve the end results were identified. That in turn calls for working out differentiated surgical strategies. PMID- 20361612 TI - [Telomerase level versus spliced hTERT-specific RNA forms in cervical carcinoma]. AB - An attempt was made to identify molecular markers of different clinical stages of cervical carcinoma caused by papilloma virus (HPV). Presence of viral genome, telomerase level and expression of a gene, which coded the catalytic activity of that enzyme (hTERT), were assayed in 89 patients. HPV (type 16) genome harboring tumors were detected in 73% which was in conformity with the literature and our own data. Telomerase was identified (TRAP) in all tumors and tumor cells cultured in vitro. hTERT-specific RNA was found in all tumor samples, however, increase in its expression was insignificant. As far as the three markers are concerned, no significant differences between clinical stages of tumor were reported. PMID- 20361613 TI - [Radical abdominal tracheolectomy: technical aspects]. AB - P.A. Herzen Research Institute of Oncology, Moscow The paper presents our experience with radical tracheolectomy carried out in 54 patients with invasive cervical carcinoma to preserve fertility. An original procedure designed to assure adequate uterine blood supply was used. Short-term oncological and functional results are discussed. PMID- 20361614 TI - [Study of dual ("joker") function of glucose in cancer patients]. AB - A relationship was studied between generation of glucose-induced reactive oxygen species capable of causing damage to DNA (genotoxic or G-effect) and insulin secretion (endocrine or hormonal effect - H-effect) in primary menopausal patients with endomrnetrial carcinoma (EC) (32) or colonic cancer (CC) (16). The study group was compared with healthy menopausal women (25) and patients with an impaired glucose tolerance (IGT) (21). Besides, we examined 32 menopausal patients (CC--6 and EC--26) more than 12 months after surgery. The following basic patterns were established: (1) H-effect was reported in EC-1 and 1GT groups nmore often than in healthy peers and those with EC-2: (2) G-effect tended to prevail in CC patients and those with EC-2 and in patients with EC-1 twelve months after operation; (3) G-effect occurred more often in primary EC patients, particularly, those with EC-2 (71%) and IGT (58%) (as compared with CC patients (33%) and healthy females (p < or = 0.001). It is suggested that a comparison of the two effects might provide a criterion for use of relevant means of prevention of certain malignancies or correction of disorders in cancer patients following radical treatment. PMID- 20361615 TI - [Survival in non-metastatic clear-cell renal cancer]. AB - Adjusted survival rates alongside 3-, 5- and 7-year cumulative indices were identified using qualitative and quantitative morphological data on cellular nuclei in 100 patients with non-metastatic clear-cell renal cancer. Significant differences were established between survival rates in tumor stages pT1a-3aN0M0 and pT3bN0M0, I and III, II and III as well as I and III, IV and III and III, IV. PMID- 20361617 TI - [Mammographic screening: results and perspectives in evaluation of reproductive health and prevention of cancer]. AB - 8542 local women, aged over 40, were screened using digital high-sensitivity equipment. High incidence of hormonal dysfunction of the breast and other breast diseases in healthy subjects were reported (60.1% +/- 9.3) (diffuse hormonal dysfunction--33.8% +/- 14.6). Early breast tumors (up to 1 cm), which generally remain undetectable, amounted to 0.19%. It was shown that mammographic data may be used in forming groups of risk for pre-morbid or morbid pathology among those requiring etiotropic therapy. In this connection, the role of timely medical advice can hardly be overestimated. PMID- 20361616 TI - [Clinical treatment outcome of grade III, non-small cell bronchogenic carcinoma using "whole-body" gamma-knife system]. AB - The results of treatment of 80 patients with non-small cell lung cancer using the Chinese-made "Whole-Body" gamma-knife system were analyzed. Primary focus and involved lymph nodes were exposed. Neither gap between primary focus and involved lymph node or nodes, nor organs of the mediastinum were exposed. Exposure regimens were: STD = 4 Gy (2.5 - 10 Gy) 5 times a week; TTD=48 Gy (27-52 Gy) per primary focus and 4 Gy (3-6 Gy) 5 times a week; TTD = 43.5 Gy (30-52 Gy) per lymph nodes (105.6 - 150 Gy = equ.). Complete response was observed in 27.5% (22/80), partial - 42.5% (34/80). Overall survival was 61.3% among those sick for one year; 41.5%--2 years and 20.75%--3 years (mean survival time--20 months). PMID- 20361618 TI - [An investigation of extracellular HER-2/NEU domain level in blood serum from breast cancer patients]. AB - A series of 159 tests on HER2 ECD in blood serum from breast cancer patients established the following correlations: enhanced levels of the marker occurred more often in patients with multiple metastases to different organs alongside those with bone metastases; patients in loco-regional relapse tended to show elevated levels too. It is suggested that the method be used for prognosis and monitoring. PMID- 20361619 TI - [Polyradiomodification as component of combined treatment of rectal cancer: rationale and results]. AB - The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented. PMID- 20361620 TI - [Extended preoperative course of radiotherapy as component of combined and complex treatment of locally-advanced ampular rectal cancer]. AB - Sixty-two patients were treated for locally-advanced ampular rectal cancer at the Center's Clinic (2004-2008). Extended preoperative course of radiotherapy plus 5 = fluorouracil chemomodification was given to 55 patients (group 1) and the same plus hyperthermia--to 27 (group 2). Radiation injuries were reported in 37.1% (group 1) and 29.6% in group 2. Surgical complications occurred in 10 (group 1) (32.2%) and 8 (group 2) (32%). Relapse was registered in 3 (group 1) (12.5%) and 3 (group 2) (13.6%). Overall 3-year survival (group 1)--82%; (group 2)--63.9%; 3 year relapse-free survival (group 1)--69.8%; (group 2)--52.2%. PMID- 20361621 TI - [Cytological methods for the diagnosis of pleuritis]. AB - Data are presented on a cytological examination of 2948 patients with pleuritis carried out during 7 years. Routine methods alongside centrifuging, cytological material staining, immunocytochemical and morphometric procedures were used. Each stage of the investigation was evaluated. Thanks to use of complex procedures, sensitivity of cytological methods for pleuritis diagnosis was raised to 95.2%, specificity--to 100%. PMID- 20361622 TI - [Emotional burnout among oncologists]. AB - The burnout syndrome is characteristic of medical profession because doctors are involved with people who are in great trouble; moreover, they are required to engage patients and maintain close psychological interaction with them. An analysis of questionnaires on problems of patient-doctor communication showed that specialized programs of psychological training should be created to help oncological doctors avoid burnout. PMID- 20361623 TI - [Mentality of cancer patients]. AB - Cancer ruins the patient's daily routine and causes anxiety thus affecting adaptation. An analysis of past conversations gives a glimpse of psychological problems tormenting cancer patients. The paper gives a glimpse in adaptation at the crux of a crisis and evaluates the role and potential of anxiety which can help go through it. PMID- 20361624 TI - [Investigation of accumulation of photosensitizer photoditazin in pulmonary neoplasm]. PMID- 20361625 TI - [Endometrial stromal sarcoma: complete response to therapy with aromatase inhibitor, anastrozole]. PMID- 20361626 TI - [The contribution made by S. N. Alexandrov to research in radio-oncology and radio-gerontology (the 90th birthday)]. PMID- 20361627 TI - [Communication in clinical oncology]. PMID- 20361628 TI - [Immune response in toxoplasmosis after mucosal immunization with Toxoplasma gondii antigens]. PMID- 20361629 TI - [Optimization of serological diagnosis of cystic echinococcosus (granulosus) infection]. AB - The diagnostic effectiveness of instrumental analysis of the concentration of specific antibodies, which was expressed in antibody units and titers, was compared in the test system of enzyme immunoassay using Echinococcus granulosus on 76 serum samples from patients with echinococcosis. The factors of possible influence on the instrumental readings of enzyme immunoassay are presented. A correlation was found in the specific antibody concentrations expressed in antibody units and titers. PMID- 20361630 TI - [Endogenous intoxication syndrome in children with mixed enteric parasitoses]. AB - The degree of endogenous intoxication and the activation of lipid peroxidation products (LPO) were studied in patients with enteric parasitoses. The findings suggest that the expression of medium-molecular-weight peptides in relation with the values of LPO is of importance in the pathogenesis of parasitoses. PMID- 20361631 TI - [Echinococcosis complicated by paecilomycosis]. AB - Two hundred and thirty-six echinococcosis patients aged 17 to 70 years were examined for paecilomycosis. Seventy-five subjects of different ages who were considered to be clinically healthy were prepared as a control. Of them who had physiological parameters of blood fungi, 24 subjects, including 9 subjects aged 17 to 23 years and 15 subjects aged 15 to 30 years, were eligible. The other examinees were patients with paecilomycosis of varying stages. Nizoral, fluconazole, diflucan, orungal, mycosyst, and teknazol, which have been tested by the authors, are proposed for use in paecilomycosis-complicated echinococcosis prior to and after surgery. It is advisable to use one fungicide. In this respect, the authors have conducted clinical trials that have yielded positive results. PMID- 20361632 TI - [The protozoan-infected brain in alcohol abusers]. AB - The paper gives the studying the brain in 57 male patients with different types of ethanol intoxication and in 14 control group subjects. The material has been examined by a complex of histological, histochemical, and morphometric studies. The different regions of the brains from those who have died and had signs of alcoholic intoxication exhibit large microorganisms that belong to protozoa, as judged from their structure are identified. They are most commonly oval in shape. The peripheral portions of the parasites' bodies are light and homogeneous and the middle ones are muddy and granular. Their cytoplasm frequently displays vacuoles and inclusions that most often looked like basophilic acicular crystals. One or two nuclei that have large hyperchromic nucleoli are located in the center of the described microorganisms or eccentrically. They are encapsulated in a number of cases. The signs of mitotic division can be seen in individual parasites. Some of them die and are prone to petrification. All these signs allow the described protozoa to be assigned to amoebas. PMID- 20361633 TI - [Left ventricular diastolic dysfunction in patients with psoriasis in the presence of chronic opisthorchiasis]. AB - Left ventricular diastolic function was studied in patients with psoriasis concurrent with chronic opisthorchiasis (CO). Seventy-five patients with psoriasis concurrent with CO, 50 patients with CO, and 20 healthy individuals were examined. Echocardiographic study (EchoCG) in the M-, B-, and Doppler modes was made in all the patients, by using the standard methods. All the examinees were found to have impaired active left ventricular relaxation that manifested itself as a longer isovolumic relaxation time, which was more pronounced in patients with psoriasis concurrent with CO. Left ventricular systolic function in these patients was preserved. In the psoriatic patients, diastolic dysfunction was characterized by impaired relaxation and it was more evident in patients with comorbidity. PMID- 20361634 TI - [The specific features of the development of the malaria mosquitoes Anopheles superpictus (Grassi 1899) in Tajikistan]. AB - In Tajikistan, the mosquitoes Anopheles superpictus (Grassi 1899) are one of the major malaria vectors. The basic habitats are the mountain and submountain landscapes of an area where this species is reckoned among the most dangerous carriers of the disease. The malaria control tactic should be determined by the species of a vector and the specific features of a protected contingent, by improving the sanitary education of people and environmental sanitation. PMID- 20361635 TI - [Study of the pathogen populations of tertian malaria and possibilities of its establishment in Kyrgyzstan]. AB - A genetic analysis has indicated that the population of the tertian malaria causative agents Plasmodium vivax in Kyrgyzstan is heterogeneous and consists of various isolates resulting from multiple carriages of the pathogens from the areas of the neighboring countries. Low genetic variability and a weak gene flow between the isolates do not contribute to the establishment of malaria in this area. Experience in controlling the epidemic outbreaks shows that active and residual foci are easily sanitized when antimalaria measures are timely and qualitatively implemented. This creates the necessary for eliminating tertian malaria in the Republic of Kyrgyzstan in the near future. PMID- 20361636 TI - [The ixodes tick fauna in Orenburg region]. AB - A total of 2665 ticks were collected in 26 administrative districts of the Orenburg Region, which belonged to 4 genera and 5 species. The proportions of the species Dermacentor marginatus, D. reticulates, Hyalomma detrium, Rhipicephalus rossicus, and Ixodes persulcatus were 60.8, 21.6, 15.6, 1, and 1%, respectively. Information is given on the species-specific composition and biodiversity of Ixodidae in different landscape and geographical zones. PMID- 20361637 TI - [Human dirofilariasis in the Tula region]. AB - The paper describes cases of dirofilariasis in the residents of Tula and the Tula Region. One of the cases does not fit into the traditional concepts. On excising a tumor in an adolescent, two live actively moving nonencapsulated helminths: a male and a female Dirofilaria repens worms were removed, which were identified at the parasitology laboratory, Center of Hygiene and Epidemiology in the Tula Region. PMID- 20361638 TI - [Antihymenolepidose activity of the compound MST-02]. PMID- 20361639 TI - [Targeted parasite control of hosts' behavior: invertebrates and fishes are intermediate hosts]. AB - The influence of parasites commonly results in the targeted natural behavior change of infected intermediate hosts, which contributes to the transition of a pathogen to a final host. At the same time the behavior manipulation mechanisms that are species-specific and common to various parasites provide the aberrations in the behavior of invertebrates and fishes under the influence of phylogenetically different parasites, which promote survival and completion of their life cycles. The influence of parasites on the metabolism of the neurotransmitter serotonin in the intermediate hosts is of considerable importance in altering the phototaxis of invertebrates and fishes. PMID- 20361640 TI - [Efficiency of use of immunoglobulin preparations for the postexposure prevention of tick-borne encephalitis in Russia (a review of semi-centennial experience)]. AB - Along with regenerated interest in passive immunization during flavivirus infections, there is an increase in the number of reports with negative opinions as to the expediency of postexposure immunoglobulin prophylaxis (IGP) of tick borne encephalitis (TBE). Analysis of the publications (since 1959) on this problem has indicated that more than half of them, including all papers with negative opinions as to IGP, contain the results of studies whose design are unsuitable for the solution of the problem associated with the efficiency of medical interventions in the context of evidence-based medicine. Analysis of the results of cohort studies has established that the timely single administration of an immunoglobulin (IG) preparation against TBE in a dose of 0.05 ml/kg body weight ensures protection on average in 79% of cases. Increasing the single dose to 0.1 ml/kg, as re-administration of IG, provides no additional protective effect. The preventive efficacy of IG preparations against TBE varies under the influence of factors, such as the infectious virus dose inoculated from tick suckling, the age of a victim, the antiviral activity of preparations with a antihemagglutinin titer of 1:20 with high infectious virus doses and the absence of reliable rapid tools for its determination on tick suckling, it is necessary to use IG with a titer of at least 1:80 and, desirably, more active in children, for postexposure prophylaxis of TBE. PMID- 20361641 TI - [The Siberian malariologist D.N. Lebedev (on the occasion of the 85th anniversary of organization of an antimalaria service in Siberia)]. PMID- 20361642 TI - [Anisocoria]. PMID- 20361643 TI - Cornea refractive surgery and scanning laser polarimetry. AB - The use of modern GDx technology (GDx-VCC and GDx-ECC) provides sufficient technical background for polarimetric diagnosis of glaucoma in eyes previously undergone corneal refractive surgery. This is of clinical importance, since the number of young myopic individuals treated with LASIK for ametropia correction is large. Most of them have not yet reached the age in which the prevalence of ahead of the ophthalmologists. Myopic persons have higher risk for glaucoma, and for those who have undergone LASIK, intraocular pressure with the usual applanation tonometric methods is underestimated. Thus the clinical importance of routine use of imaging techniques in this population is especially high. PMID- 20361644 TI - [Diagnostic and therapeutic methods in keratoconus]. AB - Keratoconus is a rare disease that appears at teenagers. This condition is diagnosed frequently and at early stages in the last years with the means of modern diagnosis (pachymetry, corneal topography). The treatments for this disease are new and efficient as corneal cross-linking and intrastromal rings. PMID- 20361645 TI - [Laser trabeculoplasty--a review]. AB - Laser therapy in open angle glaucomas represents an important step in their management, a topic of intense research during the second part of the XXth century. The initial enthousiasm generated by spectacular results obtained with minimal risks and complications, was soon tampered by their short survival. Nowadays, laser therapy is considered a second or third line therapy, alternative to surgery or intermediate stage between medication and surgery. There are selected cases in which laser therapy may be first line treatment in open angle glaucomas. PMID- 20361646 TI - [Progressive axial exophthalmy--case report]. AB - INTRODUCTION: It is being presented the clinical case of a 67 year old male patient who has been under clinical observation and treatment for 10 years. The diagnosis rests upon clinical methods, imaging techniques (ocular-orbital examination, computerized tomography and magnetic resonance imaging) as well as post-operative histopathology reports. RESULTS: The clinical diagnosis was supported by the progressive decrease in visual acuity, painful, irreducible, non pulsating axial progressive exophthalmia, associated with disorders of the ocular motility initially at the level of the RE, followed by bilateral involvement. The RE ocular-orbital ultrasound and the MRI examination point out a homogenous retro bulbar formation that caudally compresses and exceeds the optic-nerve. The mass lesion from the right orbit was afterwards partially removed by neurosurgical excision. The general treatment was initiated with steroidal and non-steroidal anti-inflammatory drugs in repetitive cures, under protection of antibiotics and anti-secretory drugs, the response to treatment being unfavorable. In time, the exophthalmia increased progressively, fact that imposed right de-compressive orbitotomy, with the surgical ablation of the lateral orbital wall. About 1 year after the neurosurgical intervention the initial clinical symptoms insidiously reinstalled throughout 3 - 4 years. The ultrasound, completed by the cranium CT and MRI examinations have identified the bilateral presence of myositis. DEBATES: Regardless of all the therapeutical means applied in time, not only the medical treatment (the systemic corticotherapy), but also the surgical one (with palliative effect), the patient's evolution was unfavorable; the axial exophthalmia persists, it is painful and irreducible. The evolution is aggravated also by the fact that both orbits have been affected; the specialty literature mentions cases with frequent unilateral involvement. CONCLUSIONS: In the case presented the axial exophthalmia is irreversible; it is determined by an inflammatory pseudotumor of both orbits, that represents a chronic inflammatory, idiopathic disease, with unpredictable clinical evolution. The diagnosis is usually one of exclusion, the complementary imaging examinations being necessary to rule out other pathologies of the orbit. PMID- 20361647 TI - Car accident leading to "traumatic" macular hole formation proven by optical coherence tomography. AB - BACKGROUND: We present the case of a car accident where the cause-consequence of the subsequent visual loss in one eye of the victim was proven by optical coherence tomography (OCT). METHODS: A 66-year-old woman was hit by a car from her right side and complained of immediate visual loss after the accident in her right eye. The patient was referred to our outpatient clinic 2.5 months after the car accident in order to elucidate the cause-consequence of the visual loss and the car accident. Following routine ophthalmologic examination OCT was performed in both eyes. RESULTS: Fundus biomicroscopy revealed a full thickness macular hole in the affected eye which was proven by OCT, while OCT showed an arrested stage of macular hole development in the unaffected left eye. Pars plana vitrectomy was performed resulting in closure of the hole. CONCLUSIONS: The arrested stage of macular hole formation seen by OCT in the fellow eye lead us to the conclusion that the accident could have been the trigger in the pathologic changes of the retina in the affected eye. The authors review the current literature related to head injury and macular hole formation. PMID- 20361648 TI - Cataract surgery (phacoemulsification) in difficult cases. AB - By presenting three cataract surgeries, we discuss the difficulties of the interventions and the key moments. Case I: Mature cataract surgery on a patient with corneal opacities (maculas). Case II: Posterior polar cataract. Case III: Small pupil, shallow anterior chamber (dilating with Malyugin ring). CONCLUSIONS: The surgery of a mature cataract on an eye with corneal opacities can be performed by a surgeon with enough experience. The final visual acuity depends on the clarity of the center of the cornea. During the operation of a posterior polar cataract we have to be prepared to the rupture of the posterior capsule, which is more frequent than in other cases. These interventions are better to be made in centers with posterior pole surgery capabilities. The Malyugin ring is a novel PMMA device, which dilates the pupil, creating decent conditions for a cataract surgery This device can be inserted and pulled out through a standard 2,8 mm incision. PMID- 20361649 TI - [Familial choroideremia--case report]. AB - We present a case of familial choroideremia followed for several years in 3 successive generations and which represented a diagnostic challenge as the final diagnosis was provided only by genetic testing. PMID- 20361650 TI - Eyelash in the anterior chamber. AB - We present the case of a patient who had surgery for cataract extraction by phacoemulsification method and that the first day after surgery one lash was found in the anterior chamber of the eye. The lash was removed the same day, the postoperative refraction being 1.0. Starting from this case, therapeutic attitude is presented in different intracameral foreign bodies. PMID- 20361651 TI - [Congenital ocular melanocytosis and delayed psycho-intellectual development--a new association?]. AB - Congenital ocular melanocytosis (COM) is an extremely rare melanocytic hyperplasia (0.038% in Caucasian population); it affects episclera and sclera. The conjunctival epithelium is not affected, as opposed to conjunctival melanosis. The pigmentation is grayish-blue and its consistency with the underlying tissues as the conjunctiva moves (deep pigmentation) is an essential diagnostic clue. COM may be isolated or associated with facial pigmentation, in the area innervated by the trigeminal nerve--known as oculodermal melanocytosis or nevus of Ota. COM may associate the following findings: iris hypercromia, iris mammillations, fundus hypercromia, uveal melanoma (most frequent choroidal melanoma) and glaucoma (10%). Melanocytes have been found in the brain, orbit, bucal mucosa in COM. PMID- 20361652 TI - [Conjunctival tumor...more than meet the eye]. AB - The authors present the case of a patient diagnosed with a conjunctival tumor. Questions are being asked about the nature of the tumor--is there just a melanocitic conjunctival tumor or a scleral extension of a intraocular tumor (that also infiltrates the cornea). A minimally invasive surgical approach is decided, with excellent intra- and post-op results. There have been no complications during 1 year of combined ophthalmologist - oncologist surveillance. PMID- 20361653 TI - [Effectiveness of olopatadine therapy in seasonal allergic conjunctivitis]. AB - PURPOSE: The study shows the antihistaminic and anti-inflammatory efficient treatment with olopatadina 0.1%. METHOD: The study group consisting of 30 patients evaluated in the ophthalmological ambulatory between the period of april august 2007 were diagnosed with acute seasonal allergic conjunctivites. Ig E and seric eosinofiles were quantified for all patients and the severity of conjunctivitis was evaluated by summing up the scores of the cardinal signs of allergic conjunctivitis: itching, conjunctival hyperemia and tearing. For a month every patients was treated with olopatadina 0.1% 2x1 drop/day. They were evaluated in day 1, day 8 and day 30. The tolerance of the treatment was judged by the reduced symptoms after olopatadine instilation. RESULTS: The score in day 1 was higher in children under 16 years of age who presented itching and tearing. After day 8 of treatment the scores droped significantly and after a month the scores decreased highly to a percentage from 60-85%. CONCLUSIONS: Choosing the best therapy in allergic conjunctivitis involves studying the mechanism implicated in triggering the allergy Olopatadina 0.1% with its double mechanism has proven to be efficient in moderate seasonal allergic conjunctivitis. PMID- 20361654 TI - IOL Tetraflex, KH 3500--presbyopia treatment. AB - INTRODUCTION: Presbyopia is a loss of accommodative capacity of the eye determined by age. The possible solutions for its treatment are spectacle correction (mono-, bi- or multifocal), multifocal contact lenses, conductive keratoplasty, excimer laser surgery and surgical solution - CLE. AIM: Four-year experience with using LOL Tetraflex KH 3500 by Lenstec. MATERIAL AND METHODOLOGY: Between 2005 and 2009, 71 eyes of 35 patients with the average age of 52 were operated at the private ophthalmological clinic 3F Microsurgery of the Eye in Kosice. The patients were selected by strict indication criteria recommended by the producer. We have evaluated the ability of the implanted lens to substitute for the presbyopic correction. The subjective criterion of patient's evaluation was the expression of content in common life situations on the scale of 1 to 10. The objective evaluation was constituted by the measurement of the accommodation width, the presence of PCO, its solution by means of YAG capsulotomy and the subsequent influence on the pseudo accommodative capacity of the lense. RESULTS: 92% of operated patients expressed their complete satisfaction with the surgery results. By objective accommodometer measurement, we have identified the average accommodation width of +1,5 dioptres on the operated eyes. The presence of PCO was discovered in 42,2% cases. All cases were treated by YAG Capsulotomy. By further observation we have tried to determine the influence of YAG Capsulotomy on the accommodation width and pseudo accommodative capacity of the eye. CONCLUSION: The selection and use of TETRAFLEX lens is an appropriate alternative to presbyopia treatment with suitable patients. PMID- 20361655 TI - Results of laser treatment-PRP to the diabetic retinopathy. AB - INTRODUCTION: Diabetic retinopathy-(DR) presents the most aggressive form of the retinopathy that has progressive movement and often it ends with optic-atrophic blindness end includes heavy complications unless carried out by laser pan retinal-photocoagulation. PURPOSE OF THE STUDY: The aim of this study was analyzing the diabetic retinopathy and impact of the PRP laser treatment, proposition of the precautious as well to managing the complications and PDR prevention. MATERIAL: In this study were presented the treatment results of diabetic retinopathy treated in the Eye's Clinic in Prishtina, during the period of time (2004-2009). There were examined and diagnosed 42 patients with DR of whom 24 males or (57.14%) and 18 females or (42.85%). In 18 patients or (27%) we have had improvement, in 35 cases or (53%) stabilization and 13 cases or (20%) worsening of state after laser treatment with PRP to DR. The most frequently complications were vitreous hemorrhage in 5 cases or (38.46%) and blindness in 3 cases or (23.07%). METHODS: There have been used statistical methods of processing and analysis according to the WHO standards. CONCLUSIONS: We consider that through an advanced education and research programs for inovative projects that meet criterias of our strategic targets to protecting the retina and optic nerv by understanding DR and PDR and developing a better laser treatment and accurately monitoring of DM, we can manage to prevent complications and heavy consequences of DR. In order to achieve this aim we have to work hard to standardized protocols. PMID- 20361656 TI - Corneal pathology and indications for corneal transplant at the Tg. Mures Ophthalmology Clinic. AB - The purpose of this study was to evaluate the incidence of corneal pathology that presents indication for cornea/transplant, treatment and follow-up of these patients. MATERIALS AND METHODS: A retrospective analysis has been undertaken at the Tg. Mures Ophthalmology Hospital. In the study we have included all patients who had corneal pathology with intact deeper ocular structures. We have examined the treatment of these cases and their admittance to corneal transplantation. RESULTS: In 2008 in 99 cases of the 3246 hospitalized patients such a corneal condition has been described that presented indication for corneal transplantation. Most common causes were corneal leucomas, corneal ulcers, bullous keratopathy and corneal dystrophies and degenerations. Fourteen patients tried to benefit from corneal transplant abroad financed by the National Health Insurance Office; others went on their own expense. All together four patients appeared for postoperative control at our Hospital. CONCLUSIONS: We have found 99 cases of corneal transplant indication at our Hospital's patients and only a fraction of them have undergone surgery. We can point out a very low level of admittance and a great need for a regional corneal transplantation centers. PMID- 20361657 TI - [New ophthalmic insert]. AB - Controlled release of drugs on ocular level is an important care for modern pharmacology. New studies targets are medical ophthalmic products with prolonged action (controlled release, target release). The hydrogel is an important segment in these studies. The purpose of this study is to assess a monolithic thermosensible hydrogel for releasing a certain medical product. MATERIAL AND METHOD: We used several materials for making thermosensible ophthalmic inserts that were processed (hydrogel synthesis, establish the inflation degree, hydrogel drug inclusion, establish the kinetics of in vitro drug releasing, in vivo studies). RESULTS: The study show that MA-G and PNIPAm basis hydrogel is a smart one that have the ability to collapse on a temperature closed to the physiological one, the result is the drug release in a desired doses. The hydrogel is perfectly tolerated, an experimental study prove that. CONCLUSIONS: Controlled release of active drug that are highly adequate to have a clinical response is based on small doses, without adverse effects. Is a target release. PMID- 20361658 TI - Enhancement of refractive results after cataract surgery and IOL-implantation with a supplementary IOL implanted in the ciliary sulcus. PMID- 20361659 TI - [Lacrimal assessment of lg E in cases with allergic conjunctivitis]. AB - PURPOSE: To present the study regarding Ig E tears dosation in cases with allergic conjunctivitis. METHOD: The Ig E tear dosation was done on two study groups--group A with 124 patients presenting allergic conjunctivitis symptoms (58 with seasonal allergic conjunctivitis, 43 with atopic allergic ocular symptoms, 23 treated with olopatadina 0.1% for 10 days) and compare group B consisting of 40 healthy patients (no local or general allergic symptoms) evaluated in the the Ophthalmology Clinic Arad between 2002-2008. The biological material used in the study was that of tears samples. For the determination of Ig E we used ELISA method, HUMAN IMUNO IG E QUANTITATION (Bethyl Laboratoires, Montgomery, TX) test. RESULTS: Significant statistic high levels of IgE concentration were observed in study group A in patients with allergic seasonal conjunctivitis (331.11 +/- 125.22 ng/ml) and patients with atopic terrain (177.18 +/- 56.70) compared to group B (67.25 +/- 8.89 ng/ml) with healthy patients. In the study group with allergic seasonal conjunctivitis there have been significant diminished IgE levels (71.70 +/- 9.94) after treatment. CONCLUSION: The method of IgE tears dosation proved to be efficient in establishing the ethiology of ocular allergies and in the screening of new cases with allergic conjunctivitis. PMID- 20361660 TI - [Personal experience in palpebral reconstruction after tumor excision]. AB - PURPOSE: To evaluate the main reconstructive methods in palpebral reconstruction after tumor excision. MATERIAL AND METHOD: We followed my personal experience of 59 cases operated in last 7 years, with tumors interesting the lower lid, the upper lid or both. After oncological resection we used the main methods in palpebral reconstruction from direct suture to complexe repair with flaps and compozite chondro-cutaneous flaps. RESULTS: We try to analize the advantages and disadvantages of the main reconstructive methods, to establish treatment strategies and to bring something new in functional eyelid reconstruction. CONCLUSIONS: The key in functional and aesthetical reconstruction of the eyelids is the correct oncological resection and anatomical reconstruction with similar tissues. PMID- 20361661 TI - [Intrastromal rings in surgical treatment of keratoconus]. PMID- 20361662 TI - [Laser trabeculoplasty--a prospective study]. AB - PURPOSE AND METHOD: Prospective study on 22 glaucoma patients (31 eyes)- pseudoexfoliation glaucoma and POAG--who underwent nonselective laser trabeculoplasty during 2007. The follow-up time is intended to be 5 years, with a preliminary report at 2 years. Our study wants to evaluate the efficiency and safety of the laser procedure. RESULTS AND DISCUSSIONS: The initial success rate was 100%; the mean IOP lowering was 11 mmHg (38%) for the pseudoexfoliation glaucoma and 5 mmHg (20%) for POAG. At 2 year interval, the success rate of trabeculoplasty was 79% for pseudoexfoliation glaucoma and still 100% for POAG. CONCLUSIONS: The preliminary results provided by our study are better than those described in the literature; we find an explanation in the fact that our group was not randomized. PMID- 20361663 TI - Keratoplasty in Hungary. AB - The first keratoplasty was performed in Hungary in 1909, but the transplantations were started in large numbers after the Second World War in Debrecen. Since 1992 a National Keratoplasty Register is functioning at the Department of Ophthalmology Debrecen. The present paper gives an overview on the current status of keratoplasty in Hungary based on the data of this Register. The number of corneal transplantations more than doubled in the past two decades. In the past 3 years (2005 to 2008) the number of transplantation seemed to stabilize around a bit more than 700. The ratio of preserved corneas disclosed a constant increase. The turning point was 1997, few years after the establishment of the Debrecen Eye Bank in 1994, when more preserved corneas were transplanted than fresh ones. The law regulating the procurement and the transplantation of corneas in our country is based on presumed consent and explicit objection which is the better type of regulation for the performance of keratoplasties in large numbers. The number of corneal transplantations in Hungary in the past decades was similar to the figures of industrial countries. PMID- 20361664 TI - [The influence of Bordetella pertussis bvgAS operon on formation and resolution of plasmid-chromosome cointegrates in Escherichia coli K12 mutants with damages in common components of the phosphoenolpyruvate:sugar phosphotransferase system]. AB - The plasmids containing the genetically marked variants of Bordetela pertussi transposon TnBP were synthesized on the base of the plasmid with thermosensitive replication. The integration frequency of these plasmids into the E.coli K12 chromosome at non-permissive temperature (42 degrees C) was determined. It was found that the frequency of forming of RSBP-induced plasmid-chromosome cointegrated in bacteria E.coli K12 deficient in HPr or Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system was decreased. The bvgAS operon from B.pertussis in trans-position restores the ability of mutant E.coli K12 to form and resolve. PMID- 20361665 TI - [Precise excision of TN5 in Escherichia coli K12 mutants with alterations in common component of phosphotransferase system and in subunits of DNA-gyrase]. AB - The effect of ptsH and gyrA mutations on precise excision (PE) of transposon Tn5 was studied in Escherichia coli K12. The conjugative plasmid with Tn5 integrated in the tet gene of Tn10 was used as a model in experiments. It was shown that mutational damage of HPr, a common component of the bacterial PEP-dependent phosphotransferase system (PTS), increased the frequency of PE. The alteration of the subunit A of DNA-gyrase (gyrA mutation) was found to enhance the frequency of PE. The ptsH mutation had the same effect. Mutational damage of the DNA-gyrase subunit B (gyrB mutation) had no effect on the frequency of PE. The data reported in this work are evidence of the necessity of the intact PTS for the balanced supercoiled DNA state maintained by DNA-gyrase. PMID- 20361666 TI - [Differentiation of geographic biovariants of smallpox virus by PCR]. AB - Comparative analysis of amino acid and nucleotides sequences of ORFs located in extended segments of the terminal variable regions in variola virus genome detected a promising locus for viral genotyping according to the geographic origin. This is ORF O1L of VARV. The primers were calculated for synthesis of this ORF fragment by PCR, which makes it possible to distinguish South America Western Africa genotype from other VARV strains. Subsequent RFLP analysis reliably differentiated Asian strains from African strains (except Western Africa isolates). This method has been tested using 16 VARV strains from various geographic regions. The developed approach is simple, fast and reliable. PMID- 20361667 TI - [Complete genomic sequence of rapidly replicating strain MB-7 of hepatitis a virus and its characterization in comparison with nucleotide sequences of other hepatitis A virus strains]. AB - Complete nucleotide sequence of genomic RNA of hepatitis A virus (HAV) rapidly replicating strain MB-7 was determined. Comparison of nucleotide and deduced amino-acid sequences demonstrated the highest level of identity of MB-7 with strain HAS-15 (above 99%) and high homology with other HAV strains (HM 175/7, CR326, and GBM/HFS) used in production of anti-hepatitis A vaccines. MB-7 was classified as subgenotype IA. Phylogenetic analysis showed that MB-7 is most closely related to the strain HAS-15 and the HAV variants circulating in Russia. Comparative analysis of genomic differences between MB-7 and HAS-15 with other HAV strains revealed among changes characteristic of MB-7 those typical of the described earlier rapidly replicating HAV strains (nt. 149-162 in 5'-untranslated region and changes in the VP3 and 2C genes). These results suggest the functional importance of changes in above-mentioned regions of HAV genome for the increased replication level of MB-7 in vitro. PMID- 20361668 TI - Community emergency/disaster preparedness. PMID- 20361669 TI - Comparison of estrogen receptors, progesterone receptors and HER-2/neu expression between primary and metastatic breast carcinoma. AB - OBJECTIVE: To determine whether receptor status and HER-2/neu status remains same in primary and metastatic breast carcinoma to corresponding lymph nodes of individual patients. METHODS: Estrogen receptors, progesterone receptors and HER 2/neu immunohistochemical stains were performed on primary and metastatic breast carcinoma to axillary lymph nodes in 100 patients. Data was collected on a Performa and age, tumour size, type, grade and expression of ER, PR and HER-2/neu on primary and metastatic tumours were recorded. RESULTS: Hormone receptor status was compared between primary and metastatic tumours. Estrogen receptor positivity was observed in 28% primary tumours which were reduced to 25% in metastatic carcinoma. Progesterone receptors were positive in 28% primary tumours as compared to 22% in metastatic tumours. Her-2/neu protein over expression was noted in 44% primary and 45% metastatic breast tumours respectively. In case to case comparison ER, PR and HER-2/neu showed 91%, 88% and 95% concordance in primary and metastatic tumours respectively. CONCLUSION: ER, PR and HER-2/neu biomarkers showed significant concordance between primary and metastatic breast carcinoma. PMID- 20361670 TI - Iodine deficiency in pregnant women of Lahore. AB - OBJECTIVE: To know extent of iodine deficiency (ID), role of thyroid enlargement (goiter) as marker of ID and current status of iodized salt intake in pregnant women of Lahore. METHODS: A cross sectional study was carried out at Institute of Chemistry, University of the Punjab, during March 2002 to September 2005. Pregnant women (n = 254) during first trimester attending antenatal clinic participated voluntarily. Iodine intake status was determined by urinary iodine (UI) excretion. RESULTS: UI excretion ranged from 34 to 142 microg/L and median value was 67 microg/L. According to international criteria, 202 (79.5%) pregnant women were iodine deficient (UI < 100 microg/L) mostly (68.8%) of mild (UI: 50-99 microg/L) degree. Moderate iodine deficiency (MID; UI < 50 microg/L) was found in 63 (24.8%) pregnant women. Among all pregnant women 80 (31.5%) had slightly visible goiter and only 87 (34.2%) were currently taking iodized salt. The difference in UI excretion between goitrous and non-goitrous pregnant women was not significant. Among iodized salt users percentage of women with MID was less, though not significant, as compared to non-users (20.7% Vs 26.9%). CONCLUSION: About one-fourth of pregnant women screened in this study are moderately iodine deficient in Lahore. These women and their neonates are at increased risk of iodine deficiency disorders. Goiter is not a good indicator of low iodine intake while iodized salt consumption is beneficial in this regard. PMID- 20361671 TI - Obstetric causes of stillbirth at low socioeconomic settings. AB - OBJECTIVE: To determine the obstetric causes for stillbirth in low socio-economic settings. METHODS: A case-control retrospective study through data analysis was conducted at a tertiary university hospital, from January to June 2008. All pregnant women diagnosed with stillbirth after 28 weeks of gestation were included in the study. They were compared with women who had live birth during the study period. Both groups were identified from the admission, and labour room registers. The risk factors studied were maternal age, parity, gestational age, hypertensive disorders of pregnancy, antepartum haemorrhage, obstructed labour and Prematurity. Stillbirth was defined as foetal death after 28 weeks of gestation. RESULTS: Of the 1011 deliveries in the selected period, there were 100 still births (98/1000 deliveries). Both nulliparity and grand multiparity were significantly associated with stillbirths (p < 0.003 and p < 0.009 respectively). From the binary logistic regression analysis, obstetric factors which were significantly associated with stillbirth were obstructed labour ( OR 16.2, CI 5.5 47), hypertensive disorders (OR 9.6 CI 4-23), abruptio placentae (OR 136, CI 52 356), placenta previa (OR 71, CI 21-230), and preterm labour (OR 15 CI 4-54). Gender was not found significantly associated with stillbirth (p < 0.432) CONCLUSION: Majority of stillbirths were due to risk factors which can be identified in the antenatal period. PMID- 20361672 TI - Cephalometric assessment of patients with adenoidal faces. AB - OBJECTIVE: To evaluate the dentofacial morphology of adenoidal faces via linear and angular measurements on lateral cephalometric tracings and compare the extent of changes with control group. METHODS: A cross sectional study was conducted from January to July 2007 at the Department of Orthodontics, de'Montmorency Institute of Dental Sciences/Punjab Dental Hospital, Lahore (tertiary health center). As a non probability purposive sampling, total of 90 cephalometric radiographs of subjects (12 to 17 years of age) 45 with adenoidal faces and 45 subjects having normal class I and orthognathic profile were collected and utilized in the study. Subject with cranio-facial anomalies and syndromes, history of previous orthodontic treatment or trauma to the head and neck region were excluded. The collected data was entered on SPSS version 10 and analyzed by using, Paired 't' test. RESULTS: Significant difference is seen among the readings showing a drastically vertical pattern of growth in dentofacial complex, except the palatal inclination angle. CONCLUSION: The findings suggest that the subjects with upper airway obstruction display excessive vertical dentofacial development, leading to a long face appearance. The condition needs to be prevented by early recognition and treatment of the causative factor. PMID- 20361673 TI - Frequency of menopausal symptoms and their impact on the quality of life of women: a hospital based survey. AB - OBJECTIVES: To asses the menopause related symptoms and to determine the impact of these symptoms on the quality of life of menopausal women. METHODS: It was a cross sectional hospital based survey conducted at the department of Obstetrics and Gynecology Isra University Hyderabad Sindh Pakistan from November 2007 to August 2008. Two hundred two women of age 40-60 years, who presented in out patient department were included. Women with induced menopause, receiving hormonal treatment, having medical problems like thyroid disorders, diabetes mellitus and hypertension and those who refused to participate were not included. Menopause specific quality of life questionnaire (MENQOL) was used to assess the frequency and severity of symptoms. Mann-Whitney U test and Pearson Co-efficient of correlation was used for statistical analysis. P value < 0.05 was considered significant. RESULTS: Mean age of women was 52.17 +/- 6.019 years. Mean length of time since menopause was 8.39 +/- 6.0 years. Most prevalent symptom within study subjects was body ache 165 (81.7%). Frequencies of some classical symptoms were 134 (66.3%) reported "hot flushes", 139 (68.8%) and 134 (66.3%) reported "lack of energy" and decrease in "physical strengths" respectively. The less frequently reported symptom was increase in facial hair 20 (9.9%). Scores of Physical domain were significantly more in postmenopausal (PM) group P < 0.002 while the scores of psychological domain were significantly high in menopause transition (MT) group P < 0.003. CONCLUSION: Menopause related symptoms had negative affect on the quality of life of postmenopausal women. PMID- 20361674 TI - Prevention of nausea and vomiting in caesarean section under spinal anaesthesia with midazolam or metoclopramide? AB - OBJECTIVE: To evaluate the efficacy and safety of bolus dose of midazolam and metoclopramide in reducing emetic symptoms during caesarean delivery under spinal anaesthesia. METHODS: In a double-blind study, 80 women undergoing elective caesarean section under spinal anaesthesia (using 0.5% bupivacaine 10 mg) were allocated randomly to receive midazolam 2 mg, or metoclopramide 10 mg at the beginning of surgery before skin incision. The frequency of nausea and vomiting, sedative score, respiratory depression, and side effects were recorded. RESULTS: The frequency of intraoperative nausea and vomiting was lower in the midazolam group compared with metoclopramide (15% versus 52.5%). Sedation scores within 3 hour postoperatively were significantly lower in the metoclopramide group. The frequency of respiratory depression was higher in midazolam group. There were some episodes of respiratory depression (respiratory rate of less than 10 bpm) in 17 patients in the midazolam group at the time of surgery treated by verbal stimulation, but no respiratory depression was seen in metoclopramide group. Neonatal outcome was similar in the two groups and all the neonates had Apgar scores > or = 8 at one and five minutes. CONCLUSIONS: A bolus dose of midazolam (2 mg) was more effective than metoclopramide (10 mg) for the prevention of nausea and vomiting in parturients patients undergoing caesarean section under spinal anaesthesia, however, further studies are needed to prove the safety of midazolam in parturient patients undergoing caesarean section. PMID- 20361675 TI - Cigarette smoke-exposed saliva suppresses cellular and humoral immune responses in an animal model. AB - OBJECTIVE: To evaluate the effects of cigarette smoke (CS)-exposed saliva on cellular and antibody responses in an animal model. METHODS: The stimulatory and non-stimulatory saliva samples were collected from 10 healthy subjects and were then exposed to CS for 20 or 80 minutes. The CS-exposed saliva samples were administrated intraperitoneally (i.p) to male Balb/c mice. Then the delayed type hypersensitivity (DTH) and antibody responses to sheep red blood cell (SRBC) was assessed. Moreover, the total white blood cells (WBC) counts and the blood lymphocytes counts were determined. RESULTS: The mean of DTH responses of animal groups received 20 minutes or 80 minutes CS-exposed saliva samples was significantly lower than that observed in control group. Moreover, The mean titer of anti-SRBC antibody was significantly lower in animal groups who received 80 minutes CS-exposed stimulatory or non-stimulatory saliva as compared to control group (P < 0.04 and P < 0.002, respectively). The mean counts of blood lymphocytes in 80 minutes CS exposed-stimulatory saliva group was also significantly lower as compared to control group (P < 0.05). CONCLUSION: These results show that the CS-exposed saliva samples have profound suppressive effects on both cellular and humoral immune response in a mouse animal model. PMID- 20361676 TI - Comparative study of efficacy, tolerability and compliance of oral iron preparations (iron edetae, iron polymatose complex) and intramuscular iron sorbitol in iron deficiency anaemia in children. AB - OBJECTIVE: To compare the efficacy, tolerability and compliance of oral iron preparations (iron edetate and iron polymaltose complex) with each other and with intramuscular iron sorbitol in iron deficiency anaemia in children. METHODS: A Randomized Controlled Trial (RCT) was carried out at the Paediatric Department of Combined Military Hospital (CMH) from January 2006 to December 2007. In total 146 children, up to 12 years age having haemoglobin (Hb%) less than 8 gm% were included. They were randomly distributed into three groups. Group A (64 cases) received oral sodium iron edetate (SIE), Group B (40 cases) received oral iron polymaltose complex (IPC) and group C (42cases) received intramuscular iron sorbitol (IS) in recommended dosages. Rise in Hb% > 10gm% was kept as desired target. Maximum duration of treatment planned was 2 weeks for parenteral iron (group C) and 12 weeks for oral iron (groups A and B). Haematological parameters- Hb%, mean corpuscular volum (MCV), mean corpuscuar haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) were measured at induction followed at 2 weeks, 4 weeks, 8 weeks and 12 weeks after start of treatment. Compliance and drop out rates were determined on each visit. Data was analyzed using SPSS version10.ANOVA was used to analyze difference in rise in Hb% at various intervals. RESULTS: Statistically significant increase in mean Hb%, MCV, MCHC after 02 weeks was observed in group C (IS). Rise in these parametes became significant in group A (SIE) and B (IPC) after 04 weeks. Peristent rise was observed in oral groups at 08 and 12 weeks. Rise in Hb% was much faster in group C (IS). It took 2 weeks to achieve mean Hb% > 10gm% and compliance rate was 40.5%, while to achieve same target, duration required was 8 weeks in group A (SIE) and 12 weeks in group B (IPC) and compliance rate was 39% and 30% respectively. Adverse effects were much more common with group A (SIE) as compared to other two groups. CONCLUSION: Intramuscular iron sorbitol is a reliable and faster alternative modality for treatment of iron deficiency anaemia in children. Short duration of treatment, sure rise in Hb% and minimal adverse effects improve compliance as compared to oral preparations. Among oral preparations, rise in Hb% is more rapid with iron edetae. While IPC gives relatively slower rise in Hb% but side effects are much less as compared to SIE. PMID- 20361677 TI - The effect of dietary and topical celecoxib on 4-nitroquinoline-1-oxide-induced lingual epithelium alternations in rat. AB - OBJECTIVE: To compare the preventive effect of dietary and topical Celecoxib (CCB), a potent inhibitor of COX-2 on 4-NQO-induced tongue SCC in rat. METHODS: Fifty male Sprague Dawley adult 3- 3.5 months old rats were used as animal model in this study. The tongue SCC was induced by a daily administration of 30 ppm 4 NQO, in drinking water, for 8 months. The rats in case groups received dietary or topical CCB. Tongue Specimens were prepared for histopathological and immunohistochemical (Ki-67) staining and or TUNEL assay were examined. Values are expressed as mean +/- SEM and analyzed with Npar Kruscal Wallis and one-way ANOVA tests. p < 0.05 was considered significant. RESULTS: The incidence of tongue precancer lesions, judged by morphological and morhometrical criteria and apoptosis/proliferation ratio, was significantly (p < 0.01) reduced by CCB. The effect of topical CCB use, at high doses, was comparable to the effect of dietary CCB. CONCLUSION: Both topical and dietary CCB have inhibitory effect on 4-NQO induced SCC on tongue. The effect of CCB is probably mediated by suppression of cell proliferation and induction of apoptosis. PMID- 20361678 TI - The pattern and distribution of malignancies reported in Hadramout, Yemen--2006. AB - OBJECTIVES: To describe the pattern of malignancies among all patients with cancer recorded in Hadramout (East of Yemen) in 2006, and to explore the association with age, sex, and site of cancer. METHODS: A retrospective descriptive study of all registered cancers (334) was carried out. Efforts were made to avoid case duplication. The neoplasms had been classified according to international classification of diseases for oncology. RESULTS: The cancers were more frequent in females (55%) than males (45%). The three most affected sites were digestive organs (20.35%), breast (14.37%), and haematopoietic system (11.98%). In the paediatric group, haematopoietic system (leukaemia) was most common. CONCLUSIONS: Digestive organs in general, with breast in females, were the most frequent sites of malignancies. Colorectal cancers were the most common cancers in digestive organs. PMID- 20361679 TI - Child labour: a public health issue. AB - Child labour is a global practice and has many negative outcomes. According to International Labour Organization, child labour is the important source of child exploitation and child abuse in the world today. The Human Rights Commission of Pakistan has estimated the number of Pakistani working children to be around 11 12 millions, out of which, at least, half the children are under the age of ten years. It portrays the society's attitude towards child care. It is therefore, essential to break this vicious cycle and hence, enable the society to produce healthy citizens. This article analyzes the determinants of child labour in the Pakistani context and its implications for child's life, in specific, and for the nation, in general, utilizing the model developed by Clemen-stone & McGuire (1991). Since this practice has complex web of causation, a multidisciplinary approach is required to combat this issue through proposed recommendations. PMID- 20361680 TI - Aplasia cutis congenita associated with azathioprine. AB - Aplasia cutis congenita is a rare skin condition characterized by the absence of localized or widespread areas of skin at birth. We are reporting a variant aplasia cutis congenita, which involved over 90% of the body surface area, which occurred in a baby born to a mother with pemphigus vulgaris who was on oral prednisolone and azathioprine. A case of extensive aplasia cutis congenita was seen and oral intake of azathioprine by the mother during pregnancy was suspected as an etiologic factor. The parents of the patient did not consent for biopsy or autopsy so the histopathological picture was not available and hence involvement of other systems could not be ascertained. Due, to financial constraints some of the investigations which might have helped in assigning the patient to a particular category of aplasia cutis such as karyotyping and CT scan brain could not be carried out. PMID- 20361681 TI - Imaging findings in a neglected case of chronic otitis media. AB - Intracranial complications of otitis media are associated with high mortality. Persistent otalgia or otorrhea while on oral antibiotics with associated neurological symptoms are ominous signs suggestive of a complication. A high index of suspicion and early diagnosis with radioimaging are essential for better outcome in these patients. We report a neglected case of chronic otitis media and discuss the magnetic resonance imaging findings. PMID- 20361682 TI - Intralobar pulmonary sequestration: a masqurader in tuberculosis prevalent population. AB - Intra pulmonary sequestration is a rare congenital disorder that is characterized by malformation of pulmonary tissue having no connection to normal tracheobronchial tree and pulmonary arteries. This is a case history of 20 years old man initially misdiagnosed as Tuberculosis and later diagnosis of intra-lobar pulmonary sequestration was confirmed. There are few reports of this rare disorder globally and we are reporting the first case of Intrapulmonary Sequestration in Pakistan. PMID- 20361683 TI - Two cases of primary laryngeal amyloidosis. AB - The larynx is a rare site of involvement of amyloidosis. We report two cases of laryngeal amyloidosis. Both patients were middle aged females with history of persistent hoarseness. Fibreoptic laryngoscopy used for diagnosis in both and debulking of the tumour was performed. Histopathological examination confirmed the diagnosis of amyloidosis. Appropriate follow up is an important part of the long-term management of the disease. PMID- 20361684 TI - Variable retinal presentations in nanophthalmos. AB - Nanophthalmos is an uncommon developmental ocular disorder characterized by a small eye with short axial length, high hyperopia and high lens/eye volume ratio due to arrested development of the globe in all directions. Different types of fundus changes can rarely occur with nanophthalmos. We describe five cases of nanophthalmos, each of them presenting with a different fundus appearance. Our case series highlights variability of pigmentary changes from retinal flecks to bone spicules and bull's eye maculopathy, which are rare in the combinations described here. PMID- 20361685 TI - Application and advantage of functional magnetic resonance imaging and blood oxygen level dependant (BOLD) imaging modality. AB - The objective of the study was to introduce the availability of bold imaging facility at Aga Khan University Hospital Karachi for the first time in Pakistan and also to review the practical application and advantages of functional magnetic resonance imaging (fMRI) and blood oxygen level dependant (BOLD) Imaging Procedures. The study was conducted at Aga Khan University Hospital, Karachi from August 2008 to November 2008 .Three patients were selected that had presented with intracranial space occupying lesions. They underwent Functional Magnetic Resonance Imaging (fMRI). The findings of the images were important to describe and localize the eloquent brain areas and their relationship to the underlying pathology. In conclusion this study reflected the significance of the Blood Oxygen Level Dependant (BOLD) imaging modality that can help in improved outcome of patients presenting with intracranial space occupying lesions. PMID- 20361686 TI - Prevention of depression: would it relieve the burden of morbidity? PMID- 20361687 TI - Investigating the awareness level about diabetes mellitus and associated factors in Tarlai (rural Islamabad). AB - OBJECTIVES: To determine the baseline level of awareness amongst a rural community about Diabetes Mellitus (irrespective of type 1 or type 2), its risk factors and complications. METHODS: This was a cross-sectional survey conducted at the community of Tarlai, Islamabad, Pakistan, in January of 2008. A structured questionnaire was used and 300 adults (age > or = 18 years) were assessed on their knowledge regarding awareness of Diabetes Mellitus, its risk factors and complications. All data collected was entered into SPSS version 10.0. The data was re-validated and analyzed. RESULTS: Out of the three hundred adults subjected to the survey, only 129 (43%) adults had any awareness of Diabetes Mellitus. Adults with no regular, scheduled exercise were 221 (73.7%) and 256 (85.3%) did not have healthy eating habits. Awareness of risk factors was present in 42 (14%) while awareness of the complications associated with the disease was 65 (22%). Adults which reported as never going for regular checkups to any clinic or hospital were 232 (77%). Family history of diabetes mellitus was statistically significantly associated with awareness about diabetes mellitus (65% vs 32%, p < 0.001), people who were in contact regularly with health care providers were more aware about diabetes and the associated risk factors than those who were not (71% vs 35%, p < 0.001). Sex was not associated (p = 0.28) with awareness about diabetes mellitus, nor was the educational status (p = 0.46). CONCLUSIONS: Majority of adults were unaware of Diabetes Mellitus itself and associated risk factors. Raising public awareness of the disease through outreach programmes and mass media should be planned and implemented. PMID- 20361688 TI - Cystic fibrosis in a child with situs inversus, a distinctively unusual association. AB - Cystic fibrosis is the most frequently witnessed potentially lethal autosomal recessive, genetic disease but its incidence is extremely low in South-Asian population. We report a case Cystic Fibrosis in a patient with Situs inversus, a condition not witnessed in medical literature of Pakistan or more captivatingly even Asia. The patient was a three and half years old male child presenting with a history of fever, cough and jaundice. Physical examination lead to the initial diagnosis of situs inversus, which was confirmed by the chest radiograph, echocardiography and ultrasound of abdomen. Further evaluations were conducted to establish the cause of respiratory symptoms. The findings of pansinusitis as evidenced by the radiography and an exceedingly high sweat chloride concentration of 100 mmol/L resulted in the conclusive diagnosis of Cystic Fibrosis. PMID- 20361689 TI - The necessity of awareness of breast cancer amongst women in Pakistan. PMID- 20361690 TI - Informed consent in developing countries: dilemmas and deliberations. PMID- 20361691 TI - Pharmageddon--a myth or reality. PMID- 20361692 TI - [166 years of Military Medical Academy in Belgrade--tradition that obliges]. PMID- 20361693 TI - [Blink and masseter inhibitory reflexes in Parkinson's disease]. AB - BACKGROUND/AIM: Idiopathic Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder with prevalence from 60 to 187 per 100 000 persons in general population. The aim of the study was to determine the abnormalities of the blink reflex (BR) and the masseter inhibitory reflex (MIR) in parkinsonian patients, as indices of the functional status of brainstem neuronal network, and abnormality level dependence on disease progression. METHODS: The investigation was conducted at the Clinic of Neurology, Clinical Center Nis, comprising a group of 60 subjects of both sexes, suffering from idiopathic Parkinson's disease in I IV stages, according to the Hoehn and Yahr scale. The control group included 30 healthy subjects of both sexes and corresponding age. Testing of the patients was performed during the "on" phase by registering MIR and BR. RESULTS: Latency of polysynaptic R2 and R2' blink reflex responses and latency of polysynaptic S2 response, as well as a silent period of MIR, are linearly shortened in the subjects with PD, and more expressed in the subsequent stages of the disease compared to the control group. CONCLUSION: There is a positive correlation between the applied neurophysiological tests results and clinical stage of PD. PMID- 20361694 TI - [Impact of rhinosinusal polyposis on CT score in patients with chronic rhinosinustis]. AB - BACKGROUND/AIM: Chronic sinusitis is a disease characterized with mucosal inflammation of nasal and paranasal sinuses for at least 12 weeks. In order to assess the extent and severity of inflammatory changes in paranasal sinuses CT score according to Lund-Mackay is the most commonly used. Recent studies show the possibility of existing different subtipes of chronic rhinosinusitis, pointing out the presence of nasal polyps and their influence on the severity of chronic rhinosinusitis. The aim of this research was to examine the influence of sinonasal polyposis on the extensity of inflammatory changes on computerized tomography (CT), evaluated by the Lund-Mackay CT score. METHODS: A prospective study compared the Lund-Mackay CT score values between the patients with chronic rhinosinusitis associated with nasal polyps and those without them. We determined mean values of the total CT score in both groups of the patients, as well as mean values of CT score for each group of sinuses and ostiomeatal complexes. RESULTS: The study included 90 patients, 47 males and 43 females, 45-year old on average, diagnosed with chronic rhinosinusitis on the basis of diagnostic algorithm. The group with uncomplicated chronic rhinosinusitis (without nasal polyps) consisted of 30 patients and the group with complicated chronic rhinosinusitis (with nasal polyps) of 60 patients. Observing these two groups of patients revealed statistically highly important intergroup difference in CT score for each group of sinuses and ostiomeatal complexes. The mean value of total CT score in the group with uncomplicated chronic rhinosinusitis was 4.37 while in the group with complicated chronic rhinosinusitis it was 16.05 (p < 0.01). CONCLUSION: Chronic rhinosinusitis complicated by sinonasal polyposis is characterized with more extensive inflammatory changes on CT and, consequently, with higher CT score for each group of sinuses and ostiomeatal complexes, as well as higher total CT score. PMID- 20361695 TI - [Topographic localization of an intraocular foreign body by B-scan echography]. AB - BACKGROUND/AIM: In cases of blurred optic media the ultrasound diagnostics offers useful data about eventual presence of intraocular foreign body as well as about its precise localization in the eye. The aim of this study was to retrospectively analyze echographic findings in patients with the diagnosis of intraocular foreign body with a special interest in localizations of a intraocular foreign body in the eye and the presence of an eventual infection - endophthalmitis. The aim of this study was also to confirm the localization of intraocular foreign body by echography and to test the precision of this method. METHODS: We performed analysis of all cases that had been referred to the ultrasound diagnostices, in which the presence of intraocular foreign body had been confirmed in the period of one year. All examinations were done with B-scan and were confirmed during the surgery - vitrectomy. RESULTS: In the one-year period we were contacted by 27 patients with intraocular foreign body. In one injured eye the intraocular foreign body was in the lens (3.70%), in 10 injured eyes (37.03%) intraocular foreign body was in the vitreal body. In 15 patients (55.5%) intraocular foreign body was fixed in the retina. In one patient (3.70%) there was a perforating injury, intraocular foreign body was found in the retrobulbar part of the orbit. In 7 injured eyes (25.9%), with the presence of intraocular foreign body, we found signs of endophthalmitis (organized blurring in vitreal space, thickened choroid). Other accompanying echographic findings were: blood in vitreal space, haemophthalmus in 12 cases (44.4%), retinal detachment in 5 cases (18.5%) and subretinal hemorrhagies in 4 cases (14.8%). CONCLUSION: Ultrasound diagnostics can very precisely show the localization of intraocular foreign body in the eye that is very important in the choice of approach and timing of surgical treatment. Also the echographic diagnostics may find an accompanying endophthalmitis in the posterior segment of the eye, that is very important for an urgent therapeutic approach. PMID- 20361696 TI - Anticardiolipin antibodies in pathogenesis of infertility. AB - BACKGROUND/AIM: Antiphospholipid syndrome (APS) is an autoimmune disorder clinically characterized by arterial or venous thrombosis and/or specific obstetric complications and presence of antiphospholipid antibodies (aPL) in the serum. It occurs in 0.3% of pregnant women, while 1% of them have two spontaneous abortions. The aim of this study was to analyze the frequency of biphospholipid antibodies in pregnant women with recurrent spontaneous abortions. METHODS: We analyzed 60 pregnant women who had two or more recurrent miscarriages. The control group included 60 healthy pregnant women. We analyzed titres of anticardiolipin (aCL) IgG and/or IgM with high titres (> 20 U/mL), lupus anticoagulant (LAC) antibodies and anti-beta-2 glycoprotein (b2-GP1) IgG as well as parameters of coagulation status of pregnant women. RESULTS: Analyzing Spearman's rank correlation coefficient in a group of affected patients, we noticed a slightly positive correlation of lupus anticoagulants (LAC) with aCL antibodies of both classes, while the correlation with b2GP1 IgG was negative. Both classes of aCL antibodies and anti-b2GP1 IgG were in a discrete positive correlation with the given variables. In the control group, there was a lack of consistency in correlation of the study variables with LAC-aCl IgG, compared to the affected patients, and there was a standard negative coefficient of correlation with anti-b2GP1 IgG. The correlation ratio of anti-b2GP1 IgG was negative for all studied test parameters. Analysis of hemostatic parameters showed a statistically significant difference in the concentration of fibrinogen (p < 0.01) and thrombocyte count (p < 0.05) between the study and the control group of pregnant women. Lower mean values of fibrinogen (2.90 +/- 0.45 g/L) and lower thrombocyte count [(179.20 +/- 6.00) x 10(9)] were found in the study group of pregnant women with secondary infertility compared to the mean values of fibrinogen (3.60 +/- 0.55 g/L) and thrombocyte count [(236.05 +/- 5.10) x 10(9)] in the control group. Activated partial thromboplastin time and prothrombin time were statistically significantly prolonged (p < 0.05) in pregnant women with spontaneous abortions compared to controls, suggest anticoagulant activity. CONCLUSION: In pregnant women with spontaneous abortions compared to healthy pregnant women slightly positive correlation of LAC with aCL antibodies of both classes, as well as a positive correlation of aCL antibodies with anti-b2GP1 IgG exist. On the other hand, hemostatic parameters values suggest an anticoagulatnt status in the blood of pregnant women with spontaneous abortions. PMID- 20361697 TI - Comparative analysis of two different methods of anaerobic capacity assessment in sedentary young men. AB - BACKGROUND/AIM: The Wingate anaerobic test is a valid and reliable method of measuring anaerobic capacity. The aim of this study was to determine whether other modified test can be used instead of the Wingate test. METHODS: A group of 30 sedentary young men were first tested with a cycle ergometer (classic Wingate test), and then with a dynamometer during 30 s of "all out" leg extension exercise (modified Wingate test; WAnTe) in order to test anaerobic capacity. Subsequent correlations between these tests were made. RESULTS: Peak power, mean power on cycling ergometer in absolute and relative values were 463 +/- 105 W, 316.7 +/- 63.8 W, 5.68 +/- 1.17 W/kg, 3.68 +/- 0.78 W/kg, respectively. On a dynamometer absolute and relative values of maximal and mean load in kg and power in Watts were 136.54 +/- 21.3 kg, 1.67 +/- 0.26; 128.65 +/- 19.93 kg, 1.57 +/- 0.24 kg, 657 +/- 125.87 W, and 8 +/- 1.54 W/kg, respectively. There was no correlation between 5 s intervals of the classic Wingate test and WAnTe during the first, fourth and fifth intervals, but in the second (r = 0.49, p < 0.05), third (r = 0.38, p < 0.05) and last 5 s intervals (r = 0.39, p < 0.05), and also in peak power and mean power (r = 0.42, p < 0.05 and r = 0.45, p < 0.05 respectively), a significant positive correlation was detected. CONCLUSION: A modified Wingate test of leg extension on a dynamometer in sedentary young men shows a correlation with the classic Wingate test only in parameters of peak power, and mean power and the second, the third and the last 5 s intervals. Because of that it should only be used for orientation, whereas for precise measurements of anaerobic capacity the classic Wingate test should be used. PMID- 20361698 TI - [Possible factors for ankle fractures]. AB - BACKGROUND/AIM: Classification of ankle fractures is commonly used for selecting an appropriate treatment and prognosing an outcome of definite management. One of the most used classifications is the Danis-Weber classification. To the best of our knowledge, in the available literature, there are no parameters affecting specific types of ankle fractures according to the Danis-Weber classification. The aim of this study was to analyze the correlation of the following parameters: age, body weight, body mass index (BMI), height, osteoporosis, osteopenia and physical exercises with specific types of ankle fractures using the Danis-Weber classification. METHODS: A total of 85 patients grouped by the Danis-Weber classification fracture types were analyzed and the significance of certain parameters for specific types of ankle fractures was established. RESULTS: The proportion of females was significantly higher (p < 0.001) with a significantly higher age (59.9 years, SD +/- 14.2) in relation to males (45.1 years, SD +/- 12.8) (p < 0.0001). Type A fracture was most frequent in the younger patients (34.2 years, SD +/- 8.6), and those with increased physical exercises (p = 0.020). In type B fracture, the risk factor was osteoporosis (p = 0.0180), while in type C fracture, body weight (p = 0.017) and osteoporosis (p = 0.004) were significant parameters. CONCLUSION: Statistical analysis using the Danis-Weber classification reveals that there are certain parameters suggesting significant risk factors for specific types of ankle fractures. PMID- 20361699 TI - [Comparative analysis of audiometric and impedancemetric findings in workers exposed to the effects of various duration industrial noise]. AB - BACKGROUND/AIM: Industrial noise is produced in workshops due to factory machinery and tools used in technological processes. It has detrimental effect to primarily the organ of the sense of hearing, thus damaging hearing in oversensitive subjects. The aim of the study was to perform a detailed analysis of audiometric and, especially, impedancemetric parameters in workers exposed to the effects of industrial noise of various duration, as well as to determine similarities and differences in workers with differences in sensitivity to damaging effects of noise. METHODS: The study included a homogenous group of 173 industrial workers involved in the same department of a huge workshop named "Kovacica" exposed to noise level above a threshold intensity, and divided into three groups: the group I of 116 workers (232 ears) exposed to noise for 8 h in the workshop "Kovacica", the group II of 41 workers (82 ears) exposed to noise only half of the working time, and the group III of 16 workers (32 ears) exposed to the same conditions and having the normal hearing sense. The group III served as a control group. Prior to the study any workers went through a thorough anamnesis and complete ORL examination, and then they were submitted to audiometric testing. The study included only the workers with no hearing damage due to diseases, injuries nor other detrimental factors in order to be sure that the hearing findings had been caused by industrial noise. RESULTS: The results obtained by audiometric testing showed that 90.75% of the workers had hearing damage of various degrees, while 9.25% of the workers had regular hearing although had been exposed to the same conditions. More severe hearing damage was revealed in the workers of the group I. Tympanometricly, in most ears of the group I workers (65.52%) a compliance value was found to be more than 0.9 cm3, while in the majority of those of the group II (59.75%) a compliance value was in the range from 0.5 to 0.9 cm3. In the workers of the group III with no hearing damage, a compliance value for any ears was in the range from 0.1 to 0.9 cm3. Mean value of threshold reflex (98.56 dB) at 500 Hz and 1 000 Hz in the group I was increased as compared with the group II (95.6 dB) and the group III (84.38 dB). At higher frequences, 2 000 and 4 000 Hz, threshold reflex was increased in the group I (99.05 dB), and in the group II (97.6 dB) as compared with the group III (86.4 dB). The amplitude of stapedic reflex was lowest in the group I, while mean values of amplitude at 500, 1 000, 2 000 and at 4 000 Hz were 2.31, 1.38, 1 and 0.3, respectively. In the group II mean values of amplitude at 500, 1 000, 2 000 and 4 000 Hz were 2.52, 1.80, 1.30 and 0.5, respectively. In the group III mean values of amplitude at 500, 1 000, 2 000 and at 4 000 Hz were 2.36, 2.45, 2.5 and 2.08, respectively. By measuring input (rising) and output angles it was revealed that most ears of the workers in the groups I and II had rising angle ranging from 41 to 50 degrees, and in the workers with no hearing loss from 31 to 50 degrees. In the majority of the ears of the groups I and II outlet angle was in the range from 16 to 35 degrees, and in the workers with no hearing damage from 26 to 35 degrees. CONCLUSION: By audiometric and impedancemetric examinations it was determined that for the sense of hearing it is significant not only a threshold hearing expressed in the audiometric curve at various frequences, but also a threshold of unpleasantness and pain under higher intensities shown by the occurrence of stapedic reflex. The less hearing field between threshold hearing and threshold acustic reflex is, the less capabilities of hearing perception due to the occurrence of recrutment. PMID- 20361700 TI - [Impact of dental implant insertion method on the periimplant epithelial seal- experimental study on dogs]. AB - BACKGROUND/AIM: There is a controversial opinion among implantologists on the method of dental implantation that provides more favourable response of soft and bone tissues. The aim of this study was to pathohistologicaly compare the influences of one- and two-phase implant surgical methods on the periimplant epithelial tissues. METHODS: The experiment was performed on 10 dogs. Eight weeks following tooth extractions implants were inserted using one phase method on the right side of the mandible, and two-phase method on the left one. Three months after implantation the animals were sacrificed. Contact regions of epithelial and subepithelial tissues and implants were pathohistologicaly examined, the elements of analysis were scored and compared. RESULTS: Epithelial tissue was not found in the two samples of one-phase implants, while in the remainder of samples the structure of basal membrane was preserved, massive inflammatory infiltrate was found in one, and partial necrosis was found in three samples. Epithelial tissue was not found in the three samples of two-phase implants, in three samples the structure of basal membrane was intact, while in three remained samples the membrane could not be detected; moderate inflammatory infiltrate was found in four samples and massive inflammatory infiltrate in both two remained samples; tissue necrosis, which was observed in the half of the samples, was complete. In subepithelial gingival tissues around one-phase implants the number of blood vessels was increased in three samples, accompanied by the thickening and dilatation of vascular walls, proliferation of blood elements, altered vascular walls and inflammatory cell infiltrate was found in four samples. CONCLUSION: On the base of the analized characteristics of epithelial and subepithelial tissues in contact with dental implants, one-phase method of implantation showed a more favorable tissue response. PMID- 20361701 TI - [Communicable diseases prevention in the Serbian Army]. PMID- 20361702 TI - [Woman with surgical reconstruction of anal atresia who realized pregnancy with in vitro fertilisation]. AB - INTRODUCTION: Anal atresia is a congenital anomaly, very life-threatening and urgent. Surgical treatment of this anomaly consists of colostomy first, and then of anal reconstruction. CASE REPORT: We presented a 31-year old female with the surgery treatment of anal atresia in the early childhood. In the reproductive period, due to tubal infertily, the patient was included in the program of in vitro fertilization (IVF), in the Clinic for Gynecology and Obstetrics "Narodni front", Belgrade. Within this program a long protocol of ovarian stimulation was performed. Ultrasonographic and color Doppler monitoring of the patient was applied by the use of an ultrasonographic apparatus type Siemens Acuson X 150, while any hormonal examinations were performed by an Architect Abbott unit. During the IVF program, the growth of follicules was controlled by the use of ultrasonography, microcirculation of the ovaries and the uterus was marked by a power-pulsating color Doppler, and hormonal examination was performed starting from the day of stimulation up to the day of injecting Pregnyl. The patient was administered Suprefact (buserelin) sc from the 21st day of the menstrual cycle, as well as from the 3rd day of the cycle, for totally 11 days. The patient was given 29 ampoules of Gonal F (recombinant human FSH) 75 IJ im and 15 ampoules of Menopur (menotrophin) im. Due to a modified pelvic anatomy, the left ovary aspiration was disabled, while the right ovary aspired seven oocytes successfully. Three embryos were inserted in the uterus. The delivery was performed by cesarean section. CONCLUSION: In the reported patient with a modified pelvic anatomy due to four corrective surgeries of anal atresia, and tubal infertility in the reproductive period, the method of choice for the realization of pregnancy was the IVF procedure. The realized pregnancy and the delivery could be considered highly successful in regard to possible risks. PMID- 20361703 TI - [Primary ovarian malignant melanoma]. AB - BACKGROUND: Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. CASE REPORT: We presented a case of primary ovarian malignant melanoma in a 45-year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. CONCLUSION: Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor. PMID- 20361704 TI - Watermelon stomach in a patient with primary Sjogren's syndrome. AB - INTRODUCTION: Watermelon stomach (WS) or gastric antral vascular ectasia (GAVE) is a rare cause of upper gastrointestinal bleeding described in a variety of autoimmune disorders. Association of watermelon stomach with Sjogren's syndrome is extremely rare. CASE REPORT; We presented a 67-year old female with primary Sjogren's syndrome (SS) who had developed a persistent severe iron-deficiency anemia. An upper gastric endoscopy revealed the presence of gastric antral vascular ectasia (GAVE) as a cause of occult gastrointestinal bleeding. The treatment with argon-plasma coagulation was postponed as the conservative therapy with iron substitution and proton pump inhibitor led to improvement of anemia and hemoglobin levels normalization. CONCLUSION: This is the first report of WS in a patient with primary SS without the presence of coexisting autoimmune disorder. Recognition of this rare, but clinically important, cause of gastrointestinal bleeding may decrease comorbidity in patients with autoimmune disorders including primary Sjogren's syndrome. PMID- 20361705 TI - Molecular mechanisms in cardiovascular and pulmonary system. Preface. PMID- 20361706 TI - Oxidative stress in cardiovascular disease. AB - Over the last two decades, it has become increasingly clear that reactive oxygen species (ROS), including free radicals are involved in cardiovascular disease. In recent years, there has been a growing interest in the clinical implications of these oxidants. The ROS are common by-products of many oxidative biochemical and physiological processes. They can be released by xanthine oxidase, NAD(P)H oxidase, lipoxygenases, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis. Various animal models of oxidative stress support that ROS have causal role in atherosclerosis and other cardiovascular diseases. They are too reactive to be tolerated in living tissue, and aerobic organisms use sophisticated defense system, both enzymatic and non-enzymatic for prevention of overload of free radicals. In a number of pathophysiological conditions, the delicate equilibrium between free-radical production and antioxidant capability can be altered in favor of the former, thus leading to oxidative stress and increased tissue injury. This review focuses on the biochemical evidences concerning involvement of ROS in several cardiovascular diseases, namely atherosclerosis, heart failure, hypertension and ischemia/reperfusion injury. PMID- 20361707 TI - Homocysteine, hydrogen sulfide (H2S) and NMDA-receptor in heart failure. AB - Mitochondrial mechanism of oxidative stress and matrix metalloproteinase (MMP) activation was unclear. Our recent data suggested that MMPs are localized to mitochondria and activated by peroxynitrite, which causes cardiovascular remodeling and failure. Recently, we have demonstrated that elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) increase oxidative stress in the mitochondria. Although HHcy causes heart failure, interestingly, it is becoming very clear that Hcy can generate hydrogen sulfide (H2S), if the enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL) are present. H2S is a strong anti-oxidant and vasorelaxing agent. Paradoxically, it is interesting that Hcy, a precursor of H2S can be cardioprotective. The CGL is ubiquitous, while the CBS is not present in the vascular tissues. Therefore, under normal condition, only half of Hcy can be converted to H2S. However, there is strong potential for gene therapy of CBS to vascular tissue that can mitigate the detrimental effects of Hcy by converting it to H2S. This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy. PMID- 20361708 TI - Emerging molecular targets for the treatment of asthma. AB - Current therapeutic approaches for the treatment of asthma have limitations in their ability to target all the features of the disease. Indeed, existing pharmacological asthma therapies are based on decades old strategies that were developed prior to the rapid growth in knowledge stemming from cell and molecular biology in the past decade. Thus, there is an unmet need for developing new drugs to target these features along with improved efficacy and safety. In the present review, the limitations of prevalent pharmacological asthma therapy are discussed briefly, and some explanations are suggested as to why new therapeutic targets are required to treat asthma, and finally directions for novel asthma therapies are proposed. PMID- 20361709 TI - New directions in inflammation and immunity: the multi-functional role of the extracellular RNA/RNase system. AB - In the mid-eighties of the last century, extracellular-proteolipid complexes have been identified in tumor patients and circulating RNA was suggested to represent a specific secretory product of cancer cells. The presence of specific types of RNA in a variety of cancer types proved to be useful in cancer diagnosis. It has been suggested that extracellular RNA and DNA are not inert molecules, but contain biological activities. Recent data have demonstrated that extracellular RNA is likely to present the up to now undefined "natural foreign surface", serving as an initiating factor in blood coagulation in vivo. Yet, extracellular RNA seems to have even more functions. Investigations on blood-brain-barrier have shown that extracellular RNA mediates endothelial permeability. Ample success has been achieved in administrating RNase in different animal models of vascular diseases, thereby significantly delaying thrombus formation and reducing cerebral edema formation with neuroprotection in acute stroke models. Furthermore, extracellular mammalian RNA was found to decrease tumor yield in a murine model system, suggesting that extracellular RNA might trigger immune response. Finally, extracellular nucleic acids were identified as danger signals involved in innate immunity related to neutrophil-mediated bacterial killing and haemocyte activation and coagulation in the insects. Thus, a new area of research on extracellular RNA functions with promising future perspectives just started in the field of inflammation and immunity. PMID- 20361710 TI - Potential health benefits of Indian spices in the symptoms of the metabolic syndrome: a review. AB - Spices used in Indian cooking have a long history of use as medicines to prevent and treat diseases. Many studies have confirmed that spices can be useful medicines, but the major challenge is now to provide scientific evidence and plausible mechanisms for their therapeutic responses. This review focuses on the therapeutic potential of Indian spices to treat multiple symptoms of the metabolic syndrome such as insulin resistance, diabetes, obesity, altered lipid profile and hypertension. The metabolic syndrome is prevalent and has become an important financial burden to the healthcare system in both developed and developing countries. Inflammation and oxidative stress have been proposed as initiators of the metabolic syndrome, especially of insulin resistance. Natural products with anti-inflammatory and anti-oxidant properties are found in spices. Adequate doses of these compounds may be effective in treating the metabolic syndrome. Testing these potential treatments requires adequate animal models, usually rodents, so the limitations of these models are important. Furthermore, this review highlights the need for adequate legislation and regulation to ensure the safety and success of evidence-based functional foods and nutraceuticals. KEYWORDS: Spices, Diabetes, Cardiovascular disease, Metabolic syndrome, Inflammation, Oxidative stress, PMID- 20361711 TI - Pulmonary vascular remodeling in congenital heart disease: enhanced expression of heat shock proteins. AB - In congenital heart disease (CHD), mechanical wall stress by increased pulmonary artery pressure and pulmonary blood flow is believed to play a pivotal role in the pathogenesis of pulmonary plexogenic arteriopathy (PPA). The pathogenesis of this disease that involves significant pulmonary arterial remodelling, is, however, largely unknown. In the systemic circulation, upregulation of HSP-70 and HSP-27 in the arterial wall occurs in response to acute hypertension, whereas HSP 60 and increased titres of anti-HSP-60 antibodies are associated with atherosclerotic vessel disease. We looked for the involvement of HSPs in the stress response of pulmonary endothelial and vascular smooth muscle cells in different abnormal hemodynamic conditions in patients with CHDs. We analyzed the expression pattern of HSP-27, HSP-70 and HSP-60 in lung biopsies of 38 patients with CHD, using immunohistochemistry. These included 4 individuals with an essentially normal pulmonary circulation, who served as controls. Immunoreactivity against HSP-27 and also against HSP-70 was present in the pulmonary endothelium and vascular smooth muscle cells of patients and controls in a similar pattern. In contrast, expression of HSP-60 was absent in pulmonary arteries of both patients and controls. In patients with advanced PPA, cells within plexiform lesions showed strong staining for HSP-27 and HSP-70, but were again negative for HSP-60. The intensity of immunoreactivity against HSP-70 correlated inversely with medial thickness of pre-acinar arteries (r = -0.32; p = 0.04). Expression of HSP-27 and HSP-70 did not correlate with hemodynamic parameters, although immunoreactivity against HSP27 tended to be increased in cases with high pulmonary artery pressure (r = 0.37; p = 0.16) and was highest in patients with flow-associated pulmonary hypertension (p<0.01). HSP-27 and HSP-70, but not HSP-60 are engaged in the stress response of cells of small pulmonary arteries in pulmonary plexogenic arteriopathy. HSP-27 and HSP-70 are increasingly expressed in the advanced proliferative lesions of this disease. PMID- 20361712 TI - Novel multi-layer APPPA microcapsules for oral delivery: preparation condition, stability and permeability. AB - Oral therapy utilizing cell microencapsulation has shown promise in the treatment of many diseases. Current obtainable microcapsule membranes, however, show inadequate stability in the gastrointestinal (GI) environment, thus restricting the general application of live cells for oral therapy. To overcome this limitation, we have previously developed a novel multilayer alginate/poly-L lysine/pectin/poly-L-lysine/alginate microcapsule (APPPA) with demonstrated improvement on membrane stability over the frequently reported alginate/poly-L lysine/alginate (APA) microcapsules. In this study, we further examined the effects of preparation conditions on microcapsule formation, and assessed the membrane strength and GI stability. Results showed that increased membrane strength of the APPPA microcapsules was attained by using pectin with low degree of esterification as the mid-layer material, saline as the solvent for the preparation solutions and washing medium, and 0.1 M CaCl2 as the gelling solution for alginate cores. Resistance of this membrane to the simulated GI fluids was also investigated. Permeability of and release profiles from the APPPA microcapsules were found comparable to the APA microcapsules. These findings suggested that the multi-layer APPPA microcapsule formulation may have potential in oral delivery of proteins, live bacterial cells and other biomedical applications. PMID- 20361714 TI - Blood pressure lowering, fibrinolysis enhancing and antioxidant activities of cardamom (Elettaria cardamomum). AB - Elettaria cardamomum (L.) Maton. (Small cardamom) fruit powder was evaluated for its antihypertensive potential and its effect on some of the cardiovascular risk factors in individuals with stage 1 hypertension. Twenty, newly diagnosed individuals with primary hypertension of stage 1 were administered 3 g of cardamom powder in two divided doses for 12 weeks. Blood pressure was recorded initially and at 4 weeks interval for 3 months. Blood samples were also collected initially and at 4 weeks interval for estimation of lipid profile, fibrinogen and fibrinolysis. Total antioxidant status, however, was assessed initially and at the end of the study. Administration of 3 g cardamom powder significantly (p<0.001) decreased systolic, diastolic and mean blood pressure and significantly (p<0.05) increased fibrinolytic activity at the end of 12th week. Total antioxidant status was also significantly (p<0.05) increased by 90% at the end of 3 months. However, fibrinogen and lipid levels were not significantly altered. All study subjects experienced a feeling of well being without any side-effects. Thus, the present study demonstrates that small cardamom effectively reduces blood pressure, enhances fibrinolysis and improves antioxidant status, without significantly altering blood lipids and fibrinogen levels in stage 1 hypertensive individuals. PMID- 20361713 TI - Therapeutic role of L-arginine on free radical scavenging system in ischemic heart diseases. AB - Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina. PMID- 20361715 TI - Hypolipidemic activity of Hibiscus rosa sinensis root in rats. AB - The hypolipidemic activity of Hibiscus rosa sinensis (family Malvaceae) root extract was studied on triton and cholesterol-rich high fat diet (HFD) induced models of hyperlipidemia in rats. In triton WR-1339-induced hyperlipidemia, feeding with root extract (500 mg/kg body wt/day p.o.) exerted lipid-lowering effect, as assessed by reversal of plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) and reactivation of post-heparin lipolytic activity (PHLA) of plasma. The other model was fed with cholesterol rich HFD and root extract (500 mg/kg body wt/ day p.o.) simultaneously for 30 days. This also caused lowering of lipid levels in plasma and liver homogenate and reactivation of plasma PHLA and hepatic total lipoprotein lipase activity. The hypolipidemic activity of Hibiscus rosa sinensis root was compared with a standard drug guggulipid (200 mg/kg body wt/day p.o.), a known lipid- lowering agent in both models. Histopathological findings in rat liver supported the protective role of H. rosa sinensis root extract in preventing cholesterol-rich HFD-induced hepatic steatosis. PMID- 20361716 TI - EEG artifacts in the intensive care unit setting. AB - Obtaining a quality EEG in the intensive care unit (ICU) is a very rewarding experience for the EEG technologist. "Quality" is defined as a measure of excellence or state of being free from defects. It takes more than knowing how to obtain a quality record; it takes hands-on experience and time. Electroencephalography is a valuable neurodiagnostic tool in critically ill patients. However, the ICU is a challenging environment to obtain a high quality EEG tracing because artifacts are exceedingly common. Dealing with artifact effectively is an essential function of the EEG technologist. The goal of this paper is to review both physiological and nonphysiological artifacts commonly encountered in an ICU setting. How to recognize, troubleshoot, and prove that an EEG pattern is an artifact will be reviewed for the novice EEG technologist. PMID- 20361717 TI - Neurocysticercosis: fireflies in the central nervous system. AB - Neurocysticercosis (NCC) is caused by cysticerci spreading to spinal or brain tissue. NCC causes headaches, seizures, and focal neurological deficits. NCC is one of the main causes of epilepsy worldwide. NCC can cause death if it is not adequately treated. NCC is preventable through education of proper handwashing techniques proper food handling, and separation of human and pig living quarters (CDC 1998). The International League Against Epilepsy (ILAE), the World Health Organization (WHO), and other international health organizations are attempting to rid the world of NCC through education. Cysticerci create cavities in the brain and other body tissue where their tiny bodies grow sometimes into tapeworms two to seven meters in length and can live up to 25 years in the human body. On magnetic resonance imaging (MRI) wormholes appear Often times, if best practice is followed, the patient's entire body is scanned and more craters appear. Some authors have stated that cysticerci on a computed topography (CT) scan are similar to a starry sky or fireflies (Kapur et al. 2007). PMID- 20361718 TI - Utilization of paraspinal muscles for triggered EMG during thoracic pedicle screw placement. AB - A novel intraoperative neurophysiological technique for testing the integrity of the pedicle during screw fixation for spinal deformity surgery is presented. The thoracic paraspinal muscles at the appropriate level are used as the electromyogram (EMG) pick-up for direct current stimulation of the thoracic pedicle screw at that level. This technique is shown to give reliable and reproducible results. This technique is found to produce more reliable data than the methods most commonly used at this time. PMID- 20361719 TI - A new ground and reference technique for invasive EEG recordings. AB - OBJECTIVE: To demonstrate a subdermal wire electrode technique for establishing a ground (GND) and reference (REF) during long-term EEG monitoring (LTM) with intracranial electrodes. Usually, a separate GND and REF are required and this GND&REF pair can be selected contacts in the invasive electrode arrays themselves, special invasive electrodes, or standard surface disc electrodes which require frequent maintenance. We investigated the use of a pair of chronic Subdermal Wire Electrodes (SWE) for use as GND&REF. METHODS: A pair of SWEs as GND&REF was tested in nine patients undergoing invasive EEG monitoring. SWE impedances were monitored in two patients and compared to disc electrode impedances. RESULTS: Without maintenance, SWE impedances remained low and stable during the entire recording period (up to 20 days), whereas disc electrodes showed rapid impedance increase after the first day. In all nine patients, the consistent and durable integrity of the GND&REF pair of SWE allowed for a good quality EEG recording. No local skin complications were observed. CONCLUSIONS: A pair of SWE electrodes provides a GND&REF system that is easy to place, maintain, and provides a high quality recording with long-term stability when coupled with referential based EEG recording system from invasive electrodes. SIGNIFICANCE: A more efficient means of establishing a GND&REF pair during the monitoring of patients with invasive electrodes is described. PMID- 20361720 TI - What doctors expect from technologists. AB - Lack of communication between electroencephalographers (EEGers) and technologists (techs) causes frustration for both parties. EEGers have trouble reading and interpreting tests and techs are left wondering if they are providing adequate examinations so that the physician can diagnose and treat patients. This article identifies barriers to communications and offers suggestions to remove these barriers. PMID- 20361721 TI - 14 and 6 hertz positive spikes. PMID- 20361722 TI - Who needs grief counseling? A report from the Scott & White Grief Study. AB - Cluster analysis was performed on a diverse group of 69 non-clinical grievers whose loved ones died between 12-40 months prior to the study. Based on psychometric measures of both bereavement distress and growth, three distinct clusters emerged: High Grief (high distress-low growth; n = 16); High Growth (low distress-high growth; n = 32); and Low Impact (low distress-low growth; n = 21). Discriminant function analyses showed that the High Grief cluster differed robustly from the other two groups on several measures of grief adaptation and coping; the differences between the High Growth and Low Impact clusters were less pronounced. High Grief participants sought grief counseling significantly more often whereas the Low Impact grievers preferred medicinal help for symptoms if they sought any professional assistance at all. When High Growth participants sought counseling, they seemed to focus on growth-oriented dimensions rather than mere symptom relief. Of the 11 participants who sought grief counseling for their loss, 10 (91%) found the experience to be helpful. Findings are discussed in the context of meta-analytic studies of the effectiveness of grief counseling. PMID- 20361723 TI - Death preparation among the ethnic Chinese well-elderly in Singapore: an exploratory study. AB - Death preparation is an important process as it can help the elderly to achieve ego integrity at the last stage of their lives. This study aims to explore how the ethnic Chinese elderly in Singapore approach issues related to death and dying, and to identify factors that influence death preparation. Descriptive surveys with semi-structured interview questions were used. Eight ethnic Chinese older adults, recruited through purposive sampling, were interviewed. Additionally, 4 adults with a deceased parent were also interviewed to validate and complement the earlier identified themes. Results show that the current generation of Chinese elderly in Singapore do not seem to be averse to talking about issues related to death, and those who find it unnecessary to prepare for death seem to be associated with, among other factors, lesser financial assets and a strong belief in filial piety. With increasing affluence and dissolving traditions, it will be beneficial to draw the attention of the current generation of mature adults on early preparation at the final stage of the lifespan. PMID- 20361724 TI - Oppression of the bereaved: a critical analysis of grief in Western society. AB - Bereaved individuals often experience profound social pressure to conform to societal norms that constrict the experience of grief rather than support it. This article explores grief in Western society through an analysis of the underlying structures and values that are a part of this social system, utilizing the lens of critical theory. Critical theory examines social norms and conditions in order to identify and expose oppression in various contexts. This article examines the social rules that govern the expression of grief, the role of attachment, social pain, and shame as potent forces that promote compliance with social rules, and the ways that the underlying assumptions and values in Western society shape how bereaved individuals are expected to react. Implications for clinicians who work with terminally ill or bereaved individuals are then reviewed. PMID- 20361725 TI - Obituaries online: new connections with the living--and the dead. AB - This study examines online obituary pages at nine major U.S. daily newspapers seeking to understand how these sites use new technologies, and how they publicly portray people's lives and deaths. These mainstream dailies provide a forum, and potentially large audiences, for mourners who send messages to the dead, express emotion, and tell stories. They also facilitate connections between readers and build new kindsof virtual communities. This represents a departure from traditional obituary content. Indeed, the "cyber obit" now allows the bereaved to help frame the death stories and build the memorials, liberated from the linear, non-interactive formats of the past. This study builds on work of bereavement scholars as well as literature in journalism and mass communication. PMID- 20361726 TI - End-of-life concerns and care preferences: congruence among terminally ill elders and their family caregivers. AB - This study examined the end-of-life challenges, concerns, and care preferences of terminally ill elders and their family caregivers, with a focus on areas of congruence and incongruence. Ten elders and 10 family caregivers participated in separate, semi-structured, face-to-face interviews. Data analysis included team coding and thematic analysis, guided by an a priori set of categories based on the study questions. Shared challenges and concerns included experiencing decline, managing pain and discomfort, and living with uncertainty. There was also congruence regarding end-of-life care preferences, specifically the importance of quality care, treatment with dignity and respect, and avoiding unnecessary life-sustaining treatment. Areas of incongruence included the elders' difficulties in accepting dependence, their fears of becoming a burden, and desire to be prepared for death. Family caregivers were most concerned with providing adequate care to meet the elders' physical and spiritual care needs. Open family communication was associated with greater congruence. The authors discuss implications of these findings for research and intervention. PMID- 20361727 TI - Atomic-level Pd-Pt alloying and largely enhanced hydrogen-storage capacity in bimetallic nanoparticles reconstructed from core/shell structure by a process of hydrogen absorption/desorption. AB - We have achieved the creation of a solid-solution alloy where Pd and Pt are homogeneously mixed at the atomic level, by a process of hydrogen absorption/desorption as a trigger for core (Pd)/shell (Pt) nanoparticles. The structural change from core/shell to solid solution has been confirmed by in situ powder X-ray diffraction, energy dispersive spectra, solid-state (2)H NMR measurement, and hydrogen pressure-composition isotherms. The successfully obtained Pd-Pt solid-solution nanoparticles with a Pt content of 8-21 atom % had a higher hydrogen-storage capacity than Pd nanoparticles. Moreover, the hydrogen storage capacity of Pd-Pt solid-solution nanoparticles can be tuned by changing the composition of Pd and Pt. PMID- 20361729 TI - Type I collagen-functionalized supported lipid bilayer as a cell culture platform. AB - The supported phospholipid bilayer serves as an important biomimetic model for the cell membrane in both basic and applied scientific research. We have constructed a biomimetic platform based on a supported phospholipid bilayer that is functionalized with type I collagen to serve as a substrate for cell culture. To create the type I collagen-functionalized lipid bilayer assembly, a simple chemical approach was employed: lipid vesicles composed of 1-palmitoyl-2-oleoyl sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3 phosphoethanolamine-N-(glutaryl) (DP-NGPE), a carboxylic acid-functionalized phospholipid, were prepared and then fused onto an SiO(2) substrate to form a supported lipid bilayer. Subsequently, type I collagen molecules were introduced to form stable collagen-lipid conjugates via amide linkages with activated DP NGPE lipids. The binding kinetics of the conjugation process and the resultant changes in film thickness and viscoelasticity were followed using the quartz crystal microbalance with dissipation (QCM-D) monitoring. The morphology of the conjugated collagen adlayer was investigated with atomic force microscopy (AFM). We observed that the adsorbed collagen molecules tended to self-assemble into fibrillar structures. Fluorescence recovery after photobleaching (FRAP) was utilized to estimate lateral lipid mobility, which was reduced by up to 20% after the coupling of type I collagen to the underlying lipid bilayer. As a cell culture platform, the collagen-conjugated supported lipid bilayer showed promising results. Smooth muscle cells (A10) retained normal growth behavior on the collagen-functionalized platform, unlike the bare POPC lipid bilayer and the POPC/DG-NGPE bilayer without collagen. The biomimetic functionalized lipid system presented here is a simple, yet effective approach for constructing a cell culture platform to explore the interactions between extracellular matrix components and cells. PMID- 20361728 TI - Phosphorylation of the transcription factor Ets-1 by ERK2: rapid dissociation of ADP and phospho-Ets-1. AB - ERK2, a major effector of the BRAF oncogene, is a promiscuous protein kinase that has a strong preference for phosphorylating substrates on Ser-Pro or Thr-Pro motifs. As part of a program to understand the fundamental basis for ERK2 substrate recognition and catalysis, we have studied the mechanism by which ERK2 phosphorylates the transcription factor Ets-1 at Thr-38. A feature of the mechanism in the forward direction is a partially rate-limiting product release step (koff = 59 +/- 6 s(-1)), which is significant because to approach maximum efficiency substrates for ERK2 may evolve to ensure that ADP dissociation is rate limiting. To improve our understanding of the mechanism of product release, the binding of the products to ERK2 was assessed and the reaction was examined in the reverse direction. These studies demonstrated that phospho-Ets-1 (p-Ets) binds >20-fold more tightly to ERK2 than ADP (Kd = 7.3 and 165 microM, respectively) and revealed that the products exhibit little interaction energetically while bound to ERK2 and that they can dissociate ERK2 in a random order. The overall equilibrium for the reaction in solution (Keq = 250 M(-1)) was found to be similar to that with the substrate bound to the enzyme (Kint = 525 M(-1)). To determine what limits koff, several pre-steady-state experiments were performed. A catalytic trapping approach furnished a rate constant (k-ADPa) of 61 +/- 12 s( 1) for the dissociation of ADP from the abortive ternary complex, ERK2.Ets.ADP. To examine p-Ets dissociation, the binding of a fluorescent derivative (p-Ets-F), which binds ERK2 with an affinity similar to that of p-Ets, was examined by stopped-flow kinetics. Using this approach, p-Ets-F was found to bind through a single-step mechanism, with the following parameters: k-p-Ets-F = 121 +/- 3.8 s( 1), and kp-Ets-F = (9.4 +/- 0.3) X 10(6) M(-1) s(-1). Similar results were found in the presence of a saturating ADP concentration. These data suggest that koff may be limited by the dissociation of both products and are consistent with the notion that Ets-1 has evolved to be an efficient substrate for ERK2, where ADP release is, at least, partially rate-limiting. A molecular mechanics model of the complex formed between ERK2 and residues 28-138 of Ets-1 provides insight into the role of substrate docking interactions. PMID- 20361730 TI - Effects of composition and domain arrangement of biopolymer components of soil organic matter on the bioavailability of phenanthrene. AB - Bioavailability of hydrophobic organic compounds (HOCs) is an important factor affecting their fate in the environment. Molecular-level HOC-soil organic matter (SOM) interactions and associated impacts on its bioavailability were investigated in this study. Our results showed that, phenanthrene (PHE) was mainly sequestrated in aromatic domains of lignin, as indicated by liquid-state (1)H-(13)C heteronuclear multiple quantum coherence (HMQC) NMR along with solid state (13)C NMR data and information on surface domain distribution of this biopolymer as shown by its X-ray photoelectron spectroscopic data. Here, surface domain distribution was defined as the relative abundance of sorption domains at the surfaces versus that in the bulky biopolymer particles and their spatial positions. Wax had much higher sorption for PHE than cellulose, but no striking difference in degradability of wax- and cellulose-sorbed PHE was observed, which can be ascribed to much more hydrophobic surface of wax relative to that of cellulose, making it more favorable for bacteria PYR-1 attachment. This work highlighted the joint effects of functionalities and surface domain distribution of SOM on bioavailability of HOCs (e.g., PHE). PMID- 20361731 TI - Encapsulation of a hydrophobic drug into a polymer-micelle core explored with synchrotron SAXS. AB - Synchrotron small-angle X-ray scattering (SAXS) at the SPring-8 40B2 and 45XU beamlines was carried out on aqueous solutions of (PEG-P(Asp(Bzl))): partially benzyl-esterified poly(ethylene glycol)-block-poly(aspartic acid) with LE540 loaded up to 8.3 wt %, where LE540 is a very hydrophobic retinoid antagonist drug. The scattering profiles showed characteristic features for core-shell spherical micelles, confirming that P(Asp(Bzl)) forms a hydrophobic core and PEG forms a hydrophilic shell. Before the addition of LE540, a diffraction peak was observed around q = 4 nm(-1), where q is the magnitude of the scattering vector. This peak can be attributed to ordering between alpha-helices made of P(Asp(Bzl)), the so-called nonspecific hexatic arrangement. The P(Asp(Bzl)) helices disappeared as LE540 was added. This result can be interpreted by assuming a uniform distribution of LE540 in the core. By use of a core-shell spherical micelle model, the SAXS data could be well fitted for all of the samples. The analysis indicated that the core radius increases sigmoidally from 5.9 to 6.9 nm upon addition of LE540 whereas the shell radius stayed at 12.5-12.8 nm. The aggregation number that is the average number of PEG-P(Asp(Bzl))'s consisting of one micelle slightly increased from 145 to 182. PMID- 20361733 TI - Surface tensions, surface potentials, and the Hofmeister series of electrolyte solutions. AB - A theory is presented which allows us to accurately calculate the surface tensions and the surface potentials of electrolyte solutions. Both the ionic hydration and the polarizability are taken into account. We find a good correlation between the Jones-Dole viscosity B coefficient and the ionic hydration near the air-water interface. The kosmotropic anions such as fluoride, iodate, sulfate, and carbonate are found to be strongly hydrated and are repelled from the interface. The chaotropic anions such as perchlorate, iodide, chlorate, and bromide are found to be significantly adsorbed to the interface. Chloride and bromate anions become weakly hydrated in the interfacial region. The sequence of surface tensions and surface potentials is found to follow the Hofmeister ordering. The theory quantitatively accounts for the surface tensions of 10 sodium salts for which there is experimental data. PMID- 20361732 TI - Light-driven formation and rupture of droplet bilayers. AB - We demonstrate the optical manipulation of nanoliter aqueous droplets containing surfactant or lipid molecules and immersed in an organic liquid using near infrared light. The resulting emulsion droplets are manipulated using both the thermocapillary effect and convective fluid motion. Droplet-pair interactions induced in the emulsion upon optical initiation and control provide direct observations of the coalescence steps in intricate detail. Droplet-droplet adhesion (bilayer formation) is observed under several conditions. Selective bilayer rupture is also realized using the same infrared laser. The technique provides a novel approach to studying thin film drainage and interface stability in emulsion dynamics. The formation of stable lipid bilayers at the adhesion interface between interacting water droplets can provide an optical platform on which to build droplet-based lipid bilayer assays. The technique also has relevance to understanding and improving microfluidics applications by devising Petri dish-based droplet assays requiring no substrate fabrication. PMID- 20361734 TI - Reversed anionic Hofmeister series: the interplay of surface charge and surface polarity. AB - We describe a two-scale modeling approach toward anion specificity at surfaces of varying charge and polarity. Explicit-solvent atomistic molecular dynamics simulations at neutral hydrophobic (i.e., nonpolar) and neutral hydrophilic (i.e., polar) self-assembled monolayers furnish potentials of mean force for Na(+) and the halide anions F(-), Cl(-), and I(-) which are then used within Poisson-Boltzmann theory to calculate ionic distributions at surfaces of arbitrary charge for finite ion concentration. On the basis of calculated long ranged electrostatic forces and coagulation properties, we obtain the direct anionic Hofmeister series at negatively charged hydrophobic surfaces. Reversal takes place when going to negative polar or to positive nonpolar surfaces, leading to the indirect series, while for positive polar surfaces the direct series is again obtained. This is in full accordance with a recent experimental classification of colloidal coagulation kinetics and also reflects the trends of the ion specific solubility properties of proteins. A schematic Hofmeister phase diagram is proposed. Partial series reversal is understood as a transient phenomenon for surfaces of intermediate polarity or charge. PMID- 20361736 TI - Iron-catalyzed C-C bond formation at alpha-position of aliphatic amines via C-H bond activation through 1,5-hydrogen transfer. AB - C-C bond formation reactions that take place through organoiron species sometimes exhibit radical-like character. The reaction of N-(2 iodophenylmethyl)dialkylamine with a Grignard or diorganozinc reagent in the presence of a catalytic amount of Fe(acac)(3) gives the product resulting from arylation, alkenylation, or alkylation of the sp(3) C-H bond next to the amine group in good to excellent yield. Mechanistic studies including labeling experiments indicate that the reaction involves radical translocation triggered by the formation of a radical-like species by removal of the iodide group. PMID- 20361735 TI - Kinetic assembly of near-IR-active gold nanoclusters using weakly adsorbing polymers to control the size. AB - Clusters of metal nanoparticles with an overall size of less than 100 nm and high metal loadings for strong optical functionality are of interest in various fields including microelectronics, sensors, optoelectronics, and biomedical imaging and therapeutics. Herein we assemble approximately 5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, that contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces. The cluster size and optical properties are tuned as a function of particle volume fractions and polymer/gold ratios to modulate the interparticle interactions. The close spacing between the constituent gold nanoparticles and high gold loadings (80-85 w/w gold) produce a strong absorbance cross section of approximately 9 x 10(-15) m(2) in the NIR at 700 nm. This morphology results from VDW and depletion attractive interactions that exclude the weakly adsorbed polymeric stabilizer from the cluster interior. The generality of this kinetic assembly platform is demonstrated for gold nanoparticles with a range of surface charges from highly negative to neutral with the two different polymers. PMID- 20361737 TI - Photoarylation of alkenes and heteroaromatics by dibromo-BINOLs in aqueous solution. AB - The photochemistry of 6,6'-dibromo-BINOL (BINOL = 2,2'-dihydroxy-1,1'-binaphthyl) under mild basic conditions and its methyl and triisopropylsilyl ethers has been investigated in neat and aqueous acetonitrile through product distribution analysis and laser flash photolysis. Arylation and alkylation have been successfully achieved in the presence of allyltrimethylsilane, ethyl vinyl ether, pyrrole, pyridine, thiophene, benzene, and indole. Such a photoreactivity offers a metal and protecting group free synthetic protocol toward mono- and disubstituted 6-aryl/alkyl BINOLs, since the BINOL chirality is preserved in the photoactivation process. PMID- 20361738 TI - Synthesis and characterization of cadmium phosphide quantum dots emitting in the visible red to near-infrared. AB - The synthesis of high-quality cadmium phosphide quantum dots with emission wavelength maxima in the range from 1200 to approximately 760 nm are reported. The results demonstrate that the nucleation and growth linked with the optical properties can be controlled by the temperature, the growth time, and the addition of ligands such as oleylamine and trioctylphosphine. Photoelectrochemical investigations revealed that the cadmium phosphide QD derivatized electrodes show an optical response and that photocurrents of several nanoamperes per square centimeter can be obtained upon illumination. PMID- 20361739 TI - Non-, micro-, and mesoporous metal-organic framework isomers: reversible transformation, fluorescence sensing, and large molecule separation. AB - For the first time, three novel metal-organic framework (MOF) isomers with hierarchical channel sizes of nonpore or micropore or mesopore were successfully prepared by simply controlling the amounts of solvent or/and reaction temperatures/time. Strikingly, we have demonstrated the reversible transformation between the microporous and mesoporous MOFs triggered by solvent or/and temperature perturbation. The desolvated microporous MOF has been evaluated to be a promising luminescent probe for detecting small molecules, and the mesoporous MOF could be the stationary phase in high-performance liquid chromatography (HPLC) for size-exclusion separation of large dye molecules. PMID- 20361740 TI - Combination of noncovalent mass spectrometry and traveling wave ion mobility spectrometry reveals sugar-induced conformational changes of central glycolytic genes repressor/DNA complex. AB - The central glycolytic genes repressor (CggR) is a 37 kDa transcriptional repressor protein which plays a key role in Bacillus subtilis glycolysis by regulating the transcription of the gapA operon. Fructose-1,6-bisphosphate (FBP), identified as the effector sugar, has been shown to abolish the binding cooperativity of CggR to its DNA target and to modify the conformational dynamics of the CggR/DNA complex. In the present study, noncovalent mass spectrometry (MS) was used to obtain deeper insights into FBP-dependent CggR/DNA interactions. The effect of FBP binding on CggR alone and on CggR/DNA complexes was examined using automated chip-based nanoelectrospray MS and traveling wave ion mobility mass spectrometry (IM-MS). Our results revealed that tetrameric CggR dissociates into dimers upon FBP binding. Moreover, FBP binding to CggR/DNA complexes triggers disruption of intermolecular protein/protein interactions within the complex, significantly modifying its conformation as evidenced by a 5% increase of its collision cross section. For the first time, the use of IM-MS is reported to probe ligand-induced conformational modifications of a protein/DNA complex with an emphasis on the comparison with solution-based techniques. PMID- 20361741 TI - Biological semiconductor based on electrical percolation. AB - We have developed a novel biological semiconductor (BSC) based on electrical percolation through a multilayer three-dimensional carbon nanotube-antibody bionanocomposite network, which can measure biological interactions directly and electronically. In electrical percolation, the passage of current through the conductive network is dependent upon the continuity of the network. Molecular interactions, such as binding of antigens to the antibodies, disrupt the network continuity causing increased resistance of the network. A BSC is fabricated by immobilizing a prefunctionalized single-walled carbon nanotubes (SWNTs)-antibody bionanocomposite directly on a poly(methyl methacrylate) (PMMA) surface (also known as plexiglass or acrylic). We used the BSC for direct (label-free) electronic measurements of antibody-antigen binding, showing that, at slightly above the electrical percolation threshold of the network, binding of a specific antigen dramatically increases the electrical resistance. Using anti staphylococcal enterotoxin B (SEB) IgG as a "gate" and SEB as an "actuator", we demonstrated that the BSC was able to detect SEB at concentrations of 1 ng/mL. The new BSCs may permit assembly of multiple sensors on the same chip to create "biological central processing units (CPUs)" with multiple BSC elements, capable of processing and sorting out information on multiple analytes simultaneously. PMID- 20361742 TI - Asymmetric synthesis of new chiral beta-amino acid derivatives by Mannich-type reactions of chiral N-sulfinyl imidates with N-tosyl aldimines. AB - New chiral beta-(sulfonylamino)sulfinylimidates are synthesized in high overall yield and excellent diastereomeric excess via highly anti-selective Mannich-type reactions of chiral N-tert-butanesulfinyl imidates with N-tosyl aldimines. Deprotection of the beta-(sulfonylamino)sulfinylimidates gave access to enantiopure imidate hydrochlorides in high yields, as useful intermediates for an easy transformation to new chiral beta-sulfonylamino amides upon simple heating in chloroform. Hydrolysis of the imidate hydrochlorides afforded the corresponding chiral beta-sulfonylamino esters with >98% ee as new chiral beta amino acid derivatives. PMID- 20361743 TI - Impact of nature and length of linker incorporated in agonists on toll-like receptor 9-mediated immune responses. AB - Oligodeoxynucleotides containing unmethylated CpG motifs act as ligands of Toll like receptor 9 (TLR9). We previously reported a novel class of TLR9 agonists, referred to as immune-modulatory oligonucleotides (IMOs), in which two 11-mers of the same sequence are attached via their 3'-ends through a 1,2,3-propanetriol linker and contain a synthetic immune-stimulatory motif, Cp7-deaza-dG. In the present study, we have examined the impact of length, nature, and stereochemistry of the linker incorporated in agonists for TLR9 activation. The new linkers studied include (S)-(-)-1,2,4-butanetriol, 1,3,5-pentanetriol, cis,cis-1,3,5 cyclohexanetriol, cis,trans-1,3,5-cyclohexanetriol, 1,3,5-tris(2 hydroxyethyl)isocyanurate, tetraethyleneglycol, and hexaethyleneglycol in place of 1,2,3-propanetriol linker. Agonists with various linkers are studied for TLR9 mediated immune responses in HEK293 cells, human cell-based assays, and in vivo in mice. Results of these studies suggest that C3-C5 linkers, 1,2,3-propanetriol, (S)-(-)-1,2,4-butanetriol, or 1,3,5-pentanetriol, are optimal for stimulation of TLR9-mediated immune responses. Rigid C3 linkers with different stereochemistry have little effect on immune stimulation, while linkers longer than C5 reduced TLR9-mediated immune stimulation. PMID- 20361744 TI - One-pot synthesis of substituted di-hydrofurans from Lewis base-catalyzed three component condensation. AB - A one-pot synthesis of substituted dihydrofurans was developed through a Lewis base-catalyzed three-component cascade condensation between nitroalkenes, aldehydes, and 1,3-dicarbonyl compounds. The desired cyclization products were prepared with a large substrate scope (22 examples) and excellent diastereoselectivity (only trans isomers) in good to excellent yields (up to 95%). PMID- 20361745 TI - (2-Nitrophenyl)acetyl: a new, selectively removable hydroxyl protecting group. AB - The utility of the (2-nitrophenyl)acetyl (NPAc) group for the protection of hydroxyl functions is reported. (2-Nitrophenyl)acetates are readily prepared starting from the commercially available, inexpensive (2-nitrophenyl)acetic acid, and these esters are stable under a series of common carbohydrate transformations. The NPAc group can be removed selectively using Zn and NH(4)Cl without affecting a series of common protecting groups. This new protecting group is orthogonal with the commonly used tert-butyldimethylsilyl, levulinoyl, 9 fluorenylmethoxycarbonyl, naphthylmethyl, and p-methoxybenzyl groups. PMID- 20361746 TI - Radical amination with trimethylstannylated benzophenone imine. AB - Intermolecular radical amination reactions of various primary, secondary, and tertiary alkyl radicals by using trimethylstannylated benzophenone imine A as a novel radical acceptor to provide imines of type B are described. These imines are readily reduced with NaBH(4) to the corresponding secondary amines C. The novel radical amination can be combined with typical radical cyclization reactions. PMID- 20361747 TI - Cu-catalyzed oxidative amidation of propiolic acids under air via decarboxylative coupling. AB - A Cu-catalyzed aerobic oxidative amidation of propiolic acids via decarboxylation under air has been developed. Only carbon dioxide is produced as byproduct in this approach. The use of air as oxidant makes this method more useful and easy to handle. PMID- 20361748 TI - Measurement of urinary total desmosine and isodesmosine using isotope-dilution liquid chromatography-tandem mass spectrometry. AB - The current LC-MS based desmosine/isodesmosine (DES/IDS) assays may be unsatisfactory for clinical use due to lack of an appropriate internal standard or low throughput. A fast and reliable LC-MS method using a D(5)-DES as an internal standard for measuring urinary total DES/IDS was developed and validated in this study. The reportable range of this assay was 1.0 and 480.0 ng/mL. The intra- and interassay imprecision, accuracy, and recovery for quality control samples were within acceptable range (<25%). Urinary total DES/IDS level was stable at room temperature or 4 degrees C for 20 h, and for three freeze/thaw cycles. The assay was employed to measure urine samples from COPD patients and demographically matched healthy volunteers. The total urinary DES/IDS levels were approximately 3-fold higher in COPD patients compared to healthy volunteers. The suitability of using urinary free DES to estimate elastin degradation was also evaluated in a second cohort. Despite urinary free and total DES/IDS levels being highly correlated, our data suggest that urinary total DES/IDS level is a preferred biomarker for elastin degradation. These results demonstrate that the LC-MS/MS method provides sensitive, reproducible and accurate quantification of urinary total DES/IDS as a biomarker for monitoring elastin degradation in diseases such as COPD. PMID- 20361749 TI - Sequential reaction of arynes via insertion into the pi-bond of amides and trapping reaction with dialkylzincs. AB - The sequential transformation of arynes into ortho-disubstituted arenes is achieved by a one-pot procedure using formamides and dialkylzincs. This reaction proceeded via a route involving the trapping reaction of the formal [2 + 2] cycloaddition adducts or quinone methides generated by the insertion of arynes into the C=O bond of amides. PMID- 20361750 TI - A copper(II)-mediated regioselective cyclization-acetoxylation of 6,8-dien-1-ones for the synthesis of functionalized cyclopentanes. AB - This paper describes a copper(II) acetate-mediated cyclization-acetoxylation of 6,8-dien-1-ones in the presence of sodium acetate as base. A variety of functionalized cyclopentanes containing synthetic useful allylic alcohol moieties with three contiguous stereogenic centers were synthesized in moderate to good yields with moderate to high regioselectivities. PMID- 20361751 TI - ABS polymer electroless plating through a one-step poly(acrylic acid) covalent grafting. AB - A new, efficient, palladium- and chromium-free process for the electroless plating of acrylonitrile-butadiene-styrene (ABS) polymers has been developed. The process is based on the ion-exchange properties of poly(acrylic acid) (PAA) chemically grafted onto ABS via a simple and one-step method that prevents using classical surface conditioning. Hence, ABS electroless plating can be obtained in three steps, namely: (i) the grafting of PAA onto ABS, (ii) the copper Cu(0) seeding of the ABS surface, and (iii) the nickel or copper metallization using commercial-like electroless plating bath. IR, XPS, and SEM were used to characterize each step of the process, and the Cu loading was quantified by atomic absorption spectroscopy. This process successfully compares with the commercial one based on chromic acid etching and palladium-based seed layer, because the final metallic layer showed excellent adhesion with the ABS substrate. PMID- 20361752 TI - Rodlike fluorescent pi-conjugated 3,3'-bipyridazine ligand: optical, electronic, and complexation properties. AB - We report on the design and synthesis of a new quadrupolar pi-conjugated 3,3' bipyridazine D-A-D ligand. Its electronic and optical properties were investigated. Besides high fluorescence and pronounced solvatochromism, it exhibits an inherent electroactivity exploited to build an organic green light emitting device. Moreover, the ability of this ligand to complex metallic centers (Cu(I), Ni(II), Pt(II), and Ir(III)) was also investigated to access different geometries and to tune their electronic and optical properties. These preliminary results open up the synthesis of heavy-metal complexes to obtain phosphorescent emitters. PMID- 20361753 TI - Direct chemical vapor deposition of graphene on dielectric surfaces. AB - Direct deposition of graphene on various dielectric substrates is demonstrated using a single-step chemical vapor deposition process. Single-layer graphene is formed through surface catalytic decomposition of hydrocarbon precursors on thin copper films predeposited on dielectric substrates. The copper films dewet and evaporate during or immediately after graphene growth, resulting in graphene deposition directly on the bare dielectric substrates. Scanning Raman mapping and spectroscopy, scanning electron microscopy, and atomic force microscopy confirm the presence of continuous graphene layers on tens of micrometer square metal free areas. The revealed growth mechanism opens new opportunities for deposition of higher quality graphene films on dielectric materials. PMID- 20361755 TI - Synthesis, characterization, and catalytic properties of new electrophilic iridium(III) complexes containing the (R)-(+)-2,2'-bis(diphenylphosphino)-1,1' binaphthyl ligand. AB - The oxidative addition of MeI to the Ir(I) square-planar complex IrI(CO)((R)-(+) BINAP) where (R)-(+)-BINAP = (R)-(+)-2,2'-bis(diphenylphosphino)-1,1' binaphthyl)) results in the formation of two diastereomers in a 2:1 ratio of the Ir(III) oxidative addition product IrI(2)(CO)(Me)((R)-(+)-BINAP) (4a and 4b) in a 85% overall yield. Upon iodide abstraction from the diastereomeric mixture with 2 equiv of AgSbF(6) in the presence of diethyl isopropylidene malonate (DIM), two diastereomers of the dicationic complex [Ir(CO)(Me)(DIM)((R)-(+) BINAP)][SbF(6)](2) (5) are formed in a 90% yield with a ratio of 9:1. One diastereomer of the diiodide complex 4 and one diastereomer of the dicationic complex 5 have been characterized by X-ray diffraction. An anion exchange reaction of 5 with NaBAr(4)(f-) (BAr(4)(f-) = B(3,5-(CF(3))(2)C(6)H(3))(4)) affords [Ir(CO)(Me)(DIM)((R)-(+)-BINAP)][BAr(4)(f)](2) (6) in quantitative yield. Both 5 and 6 are active Lewis acid catalysts for the polarized Nazarov cyclization and the Diels-Alder reaction. In the Nazarov cyclization, when NaBAr(4)(f) is added as a cofactor for the reaction catalyzed by 5 or 6, the resultant oxyallyl cation intermediate from the 4pi conrotation undergoes a Wagner-Meerwein rearrangement to afford spirocyclic cyclopentenones in modest to good yields. PMID- 20361756 TI - Reactive ballistic deposition of alpha-Fe2O3 thin films for photoelectrochemical water oxidation. AB - We report the preparation of alpha-Fe2O3 electrodes using a technique known as reactive ballistic deposition in which iron metal is evaporatively deposited in an oxygen ambient for photoelectrochemical (PEC) water oxidation. By manipulating synthesis parameters such as deposition angle, film thickness, and annealing temperature, we find that it is possible to optimize the structural and morphological properties of such films in order to improve their PEC efficiency. Incident photon to current conversion efficiencies (IPCE) are used to calculate an AM1.5 photocurrent of 0.55 mA/cm(2) for optimized films with an IPCE reaching 10% at 420 nm in 1 M KOH at +0.5 V versus Ag/AgCl. We also note that the commonly observed low photoactivity of extremely thin hematite films on fluorine-doped tin oxide substrates may be improved by modification of annealing conditions in some cases. PMID- 20361757 TI - Soft, highly conductive nanotube sponges and composites with controlled compressibility. AB - Porous carbon nanotube networks represent a type of material that can achieve both structural robustness and high flexibility. We demonstrate here controlled synthesis of soft to hard sponges with densities ranging from 5 to 25 mg/cm(3), while retaining a porosity of >99%. The stable sponge-like structure allows excellent compressibility tunable up to 90% volume shrinkage, and the ability to recover most of volume by free expansion. Electrical resistivity of the sponges changes linearly and reversibly after 300 cycles of large-strain compression. Nanotubes forming the three-dimensional scaffold maintain good contact and percolation during large-strain deformation, polymer infiltration, and cross linking process, suggesting potential applications as strain sensors and conductive nanocomposites. PMID- 20361758 TI - Reversible C-C coupling in a uranium biheterocyclic complex. AB - The C-C coupling of two molecules of 1-methylbenzimidazole was effected by a neutral uranium dibenzyl complex supported by a ferrocene 1,1'-diamide ligand. The transformation involves the C-H activation of two heterocycles and the coupling of one eta(2)-N,C-imidazolyl fragment with a coordinated 1 methylbenzimidazole ligand. The solid-state structure of this product was studied by both single-crystal and powder X-ray diffraction methods and confirms the formation of the biheterocyclic moiety. In solution, the C-C coupling event was found to be reversible, as assessed by variable-temperature (1)H and (2)H NMR spectroscopy as well as DFT calculations and reactivity studies. PMID- 20361759 TI - Antiparallel dimer and actin assembly. AB - The antiparallel dimer (APD) is a unique actin species, which can be detected in the early stages of actin polymerization. In this work, we introduce novel tools for examination of the effects of the APD on actin polymerization. We document that bifunctional methanothiosulfonate (MTS) reagents are an attractive alternative to the routinely used p-phenylene maleimide (pPDM) for APD detection, allowing for fast and efficient cross-linking under conditions of actin polymerization at neutral pH. We report also that pyrene-labeled yeast actin mutant A167C/C374A (C167PM) forms significant amounts of stable APD in solution, without chemical cross-linking or polymerization-affecting compounds, and that the kinetics of APD transformation and decay upon actin polymerization can be easily monitored. The dimerization of C167PM has been characterized in sedimentation equilibrium experiments (K(d) approximately 0.3 microM). This new system offers the advantage of assessing the effects of the APD under physiological conditions (pH, ionic strength, and Mg(2+) concentration) and testing for conformational transitions in the APD during nucleation polymerization reactions or/and in the presence of actin-interacting factors. The results obtained using two different systems (C167PM actin and polylysine-induced polymerization of alpha-actin) show that the APD decays at a rate slower than that at which the filaments elongate, revealing its transient incorporation into filaments, and confirm that it inhibits the nucleation and elongation of actin filaments. PMID- 20361760 TI - Predicting the formation and stability of amorphous small molecule binary mixtures from computationally determined Flory-Huggins interaction parameter and phase diagram. AB - The Flory-Huggins interaction parameter has been shown to be useful in predicting the thermodynamic miscibility of a polymer and a small molecule in a binary mixture. In the present paper, this concept was extended and evaluated to determine whether or not the Flory-Huggins interaction parameter can be applied to small molecule binary mixtures and if this parameter can predict the phase stability of such amorphous binary mixtures. This study was based on the assumption that a thermodynamically miscible binary system is stable and cannot crystallize, and that phase separation is essential before the individual components can crystallize. The stabilization of a binary system is thought to derive from molecular interactions between components in a solid dispersion, which are characterized by the Flory-Huggins interaction parameter. Based on DSC experiments, drug molecules (39) in the present study were classified into three different categories according to their crystallization tendency; i.e., highly crystallizing, moderately crystallizing and noncrystallizing compounds. The Flory Huggins interaction parameter was systematically calculated for each drug pair. The validity of this approach was empirically verified by hot-stage polarized light microscopy. If both compounds in the pair belonged to the category of highly crystallizing compound, the Flory-Huggins interaction predicted an amorphous or crystalline phase with approximately 88% (23 out of 26) confidence. If one or both compounds of the pair were either moderately crystallizing or noncrystallizing compounds, the binary mixture remained in the amorphous phase during the cooling phase regardless of the interaction parameter. The Flory Huggins interaction parameter was found to be a reasonably good indicator for predicting the phase stability of small molecule binary mixtures. The method described can enable fast screening of the potential stabilizers needed to produce a stable amorphous binary mixture. PMID- 20361761 TI - Diabetes correction in pancreatectomized canines by orally absorbable insulin deoxycholate complex. AB - Oral insulin therapy has great potential benefits over conventional therapy for diabetic patients as well as mimicking the physiological fate of insulin. Here we evaluated the characteristics of insulin and deoxycholate-based synthetic N(alpha)-deoxycholyl-L-lysyl-methylester (DCK) complex, and diabetes correction in pancreatectomized canines after oral administration. After the insulin/DCK complexation was made, the insulin's folding structure, stability against digestive enzymes, lipophilicity and permeability to Caco-2 monolayer were evaluated in vitro. Diabetic canines were kept under fasting conditions, and Eudragit-coated gelatin capsules containing insulin or insulin/DCK powder were singly or triply administered. Evaluation of glucodynamics, pharmacokinetics, oral glucose tolerance test (OGTT) and reproducibility were carried out. After complexation with DCK, the folding structure of insulin did not become denatured and the resistance against digestive enzymes was powerfully improved. The lipophilicity and permeability of insulin/DCK (coupling ratio up to 1:10) were also highly increased. The insulin/DCK complex, administered orally into diabetic canines at the doses of 21, 42, and 81 IU/kg, reduced the plasma glucose levels by about 28%, 44% and 67%, respectively, while the plasma insulin concentrations increased. During OGTT, insulin/DCK nearly maintained the normoglycemic state in the diabetic canines, whereas the hyperglycemic state of placebo-treated controls was not corrected. During oral administration of insulin/DCK, it repetitively showed similar therapeutic efficacy in diabetic canines for 3 days. The therapeutic efficacy of insulin/DCK was exhibited in its digestive enzyme resistance, deoxycholate-based lipophilicity for enhancing permeability and intact insulin delivery without chemical modification, providing potential oral therapeutic remedy as an alternative to injectable insulin medication. PMID- 20361762 TI - Surface functionalization of titanium with chitosan/gelatin via electrophoretic deposition: characterization and cell behavior. AB - The electrophoretic deposition (EPD) is a versatile and cost-effective technique for fabricating advanced coatings. In this study, chitosan/gelatin (CS/G) coatings were prepared on titanium substrates via EPD. The prepared coatings were characterized using fluorescence microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and shear bond strength testing. It was found that CS/G coatings had a similar macroporous structure. The gelatin content in the CS/G coatings gradually increased with the increase of the gelatin in the blend solutions. The shear bond strength of the CS/G coatings also increased with the increasing gelatin content. In vitro biological tests demonstrated that human MG63 osteoblast-like cells achieved better affinity on the coatings with higher gelatin content. Therefore, it was concluded that EPD was an effective and efficient technique to prepare CS/G coatings on the titanium surface and that CS/G coatings with higher gelatin content were promising candidates for further loading of functional agents. PMID- 20361764 TI - Thermodynamics of the hydrolysis reactions of 1-naphthyl acetate, 4-nitrophenyl acetate, and 4-nitrophenyl alpha-L-arabinofuranoside. AB - Microcalorimetry, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS) have been used to conduct a thermodynamic investigation of the hydrolysis reactions {1-naphthyl acetate(aq) + H(2)O(l) = 1-naphthol(aq) + acetate(aq)}, {4-nitrophenyl acetate(aq) + H(2)O(l) = 4-nitrophenol(aq) + acetate(aq)}, and {4-nitrophenyl alpha-L arabinofuranoside(aq) + H(2)O(l) = L-arabinose(aq) + 4-nitrophenol(aq)}. Calorimetrically determined enthalpies of reaction Delta(r)H(cal) were measured for all three reactions. However, since the positions of equilibrium for all of these reactions were found to lie very far to the right, it was only possible to set lower limits for the values of the apparent equilibrium constants K'. A chemical equilibrium model, together with pKs and standard enthalpies of reaction Delta(r)H degrees for the H(+) binding reactions of the reactants and products, was then used to calculate the values of Delta(r)H degrees for chemical reference reactions that correspond to the overall biochemical reactions that were studied experimentally. The values of Benson estimates of Delta(r)H degrees for the chemical reference reactions that correspond to the first of the above two reactions were, in all cases, within 16 kJ.mol(-1) of the results obtained in this study. Thermochemical network calculations led to Delta(f)H degrees = 286.4 kJ.mol(-1) for 1-naphthyl acetate(aq) and Delta(f)H degrees = -364.9 kJ.mol(-1) for 4-nitrophenyl acetate(aq). PMID- 20361763 TI - Arsenic binding and transfer by the ArsD As(III) metallochaperone. AB - ArsD is a metallochaperone that delivers trivalent metalloids [As(III) or Sb(III)] to the ArsA ATPase, the catalytic subunit of the ArsAB pump encoded by the arsRDABC operon of Escherichia coli plasmid R773. Interaction with ArsD increases the affinity of ArsA for As(III), conferring resistance to environmental concentrations of arsenic. Previous genetic analysis suggested that ArsD residues Cys12, Cys13, and Cys18 are involved in the transfer of As(III) to ArsA. Here X-ray absorption spectroscopy was used to show that As(III) is coordinated with three sulfur atoms, consistent with the three cysteine residues forming the As(III) binding site. Two single-tryptophan derivatives of ArsD exhibited quenching of intrinsic protein fluorescence upon binding of As(III) or Sb(III), which allowed estimation of the rates of binding and affinities for metalloids. Substitution of Cys12, Cys13, or Cys18 decreased the affinity for As(III) more than 10-fold. Reduced glutathione greatly increased the rate of binding of As(III) to ArsD but did not affect binding of As(III) to ArsA. This suggests that in vivo cytosolic As(III) might be initially bound to GSH and transferred to ArsD and then to ArsAB, which pumps the metalloid out of the cell. The As(III) chelator dimercaptosuccinic acid did not block the transfer from ArsD to ArsA, consistent with channeling of the metalloid from one protein to the other, as opposed to release and rebinding of the metalloid. Finally, transfer of As(III) from ArsD to ArsA occurred in the presence of MgATP at 23 degrees C but not at 4 degrees C. Neither MgADP nor MgATP-gamma-S could replace MgATP. These results suggest that transfer occurs with a conformation of ArsA that transiently forms during the catalytic cycle. PMID- 20361765 TI - Computational studies on metathetical and redox processes of HOCl in gas phase. III. Its self-reaction and interactions with HNOx (x = 1-3). AB - The gas-phase redox reactions of HOCl with its self and HNO(x) (x = 1-3) have been studied theoretically by ab initio quantum chemical and statistical mechanical theories. The structures of reactants, intermediate complexes, products, and transition states were optimized at the MPW1PW91/6-311+G(3df,2p) level of theory. The potential energy surface of each reaction was refined at the CCSD(T)/6-311+G(3df,2p) level of theory. The most favorable products are predicted to be ClClO + H(2)O and ClOCl + H(2)O for the HOCl self-reaction (A), H(2)O + Cl + NO for the HOCl + HNO reaction (B), H(2)O + ClNO(2) for the HOCl + HONO-t reaction (C), H(2)O + cis-ClONO for the HOCl + HONO-c reaction (D). For the HOCl + HONO(2) reaction (E), only one dehydration reaction channel was considered to produce H(2)O + ClONO(2). The rate constants of all above five reactions have been predicted at 300-3000 K by the VTST/RRKM theory. The calculation shows that the theoretical rate constants are within the upper limits of experimental results. In addition, we calculated the equilibrium constant for the Cl(2)O + H(2)O --> HOCl + HOCl reaction, which is also in reasonable agreement with experimental data within the error of the available experimental enthalpy change. PMID- 20361766 TI - Urea-induced drying of carbon nanotubes suggests existence of a dry globule-like transient state during chemical denaturation of proteins. AB - Atomistic dynamics simulations of purely hydrophobic carbon nanotubes in 8 M urea are performed to dissect the role of dispersion interactions in the denaturing power of urea. The enhanced population of urea and a paucity of water in proximity of nanotubes suggest that the stronger dispersion interaction of urea than water with nanotube triggers drying of its interior. The preferential intrusion of urea over water within nanotube interiors irrespective of their diameters directly implies a "dry globule"-like transient intermediate formation in the initial stage of protein unfolding in urea. PMID- 20361767 TI - Highly specific substrates of proteinase 3 containing 3-(2-benzoxazol-5-yl)-l alanine and their application for detection of this enzyme in human serum. AB - A set of benzoxazolyl-l-alanine derivates along with the MCA moiety (donors of fluorescence) were introduced into a proteinase 3 (PR3) substrate with a C terminal ANB-NH(2) that serves as a fluorescence acceptor. Five substrates with general formula X-Tyr-Tyr-Abu-ANB-NH(2) were synthesized, and their kinetic parameters against proteinase 3 were determined. The highest k(cat)/K(M) value, 1.5 x 10(6) M(-1) s(-1), was obtained for (Pyr)Box-Ala-Tyr-Tyr-Abu-NH(2) where (Pyr)Box-Ala stands for N-methylpyrrole benzoxazole-l-alanine. Titration of this peptide with proteinase 3 resulted in measurable fluorescence at an enzyme amount equal to 29 pmol. This substrate was selected used to detect quantifiable levels of proteinase 3 in serum samples, including those of normal subjects. For all c ANCA-positive samples (diagnosed Wegener granulomatosis), a significant increase of PR3 concentration was observed. Wegener granulomatosis is a severe autoimmune disease causing inflammation of the blood vessels. Our results clearly show that this substrate can be used for the construction of a very reliable, inexpensive, and easy to use diagnostic test for PR3 determination. PMID- 20361768 TI - Studies of single aerosol particles containing malonic acid, glutaric acid, and their mixtures with sodium chloride. I. Hygroscopic growth. AB - We describe a newly constructed electrodynamic balance with which to measure the relative mass of single aerosol particles at varying relative humidity. Measurements of changing mass with respect to the relative humidity allow mass (m) growth factors (m(aqueous)/m(dry)) and diameter (d) growth factors (d(aqueous)/d(dry)) of the aerosol to be determined. Four aerosol types were investigated: malonic acid, glutaric acid, mixtures of malonic acid and sodium chloride, and mixtures of glutaric acid and sodium chloride. The mass growth factors of the malonic acid and glutaric acid aqueous phase aerosols, at 85% relative humidity, were 2.11 +/- 0.08 and 1.73 +/- 0.19, respectively. The mass growth factors of the mixed organic/inorganic aerosols are dependent upon the molar fraction of the individual components. Results are compared with previous laboratory determinations and theoretical predictions. PMID- 20361769 TI - OH radical initiated oxidation of 1,3-butadiene: isomeric selective study of the dominant addition channel. AB - We report the first isomeric selective kinetic study of the dominant isomeric pathway in the OH initiated oxidation of 1,3-butadiene in the presence of O(2) and NO using the laser photolysis-laser induced fluorescence (LP-LIF) technique. The photodissociation of the precursor 2-iodo-but-3-en-1-ol results exclusively in the dominant OH-butadiene addition product, permitting important insight into the OH initiated oxidation mechanism. On the basis of analysis of the time dependent OH/OD signals, we have determined a rate constant for O2 addition to the hydroxyalkyl radical of 7.0(-3.0)(+7.0) x 10(-13) cm(3) s(-1), and we find a value of 1.5(-0.6)(+1.0) x 10(-11) cm(3) s(-1) for the overall reaction rate constant of the hydroxy peroxy radical with NO. We also report the first clear experimental evidence of the (E) form of the delta-hydroxyalkoxy channel through isotopic labeling experiments and provide an upper bound of 13 +/- 5% to its branching ratio. This species provides a mechanistic pathway for the formation of 4-hydroxy-2-butenal, which has been identified as a first generation end product. This isomeric selective kinetic study, together with a previous study on the minor channel of the 1,3-butadiene oxidation, yields a comprehensive picture of butadiene oxidation under high NOx conditions relevant to most regions in the continental US. PMID- 20361770 TI - Accurate and precise determination of silver isotope fractionation in environmental samples by multicollector-ICPMS. AB - High precision silver isotope ratios in environmental samples were determined by multicollector inductively coupled plasma mass spectrometry (MC-ICPMS). Purification of Ag from sample matrixes was performed by a two stage tandem column setup with use of anion and cation exchange resin, sequentially. It was found that 1% HNO(3) and 3% HCl was efficient to stabilize Ag in the final purified sample digests prior to MC-ICPMS determination. Pd at 2 mug g(-1) was added to both sample and Ag standard solution as a common doping matrix as well as an internal standard for mass bias correction. Mass discrimination and instrument drift were corrected by a combination of internal normalization with Pd and standard-sample-standard bracketing, without assuming identical mass bias for Pd and Ag. NIST SRM 978a (silver isotopic standard reference material) was used for method validation and subjected to column separation and sample preparation processes. A value of -0.003 +/- 0.010 per thousand for delta(107/109)Ag (mean and 2SD, n = 4) was obtained, confirming accurate results can be obtained using the proposed method. To the best of our knowledge, this is the first report on delta(107/109)Ag variations in environmental samples. Significant differences in Ag isotope ratios were found among NIST SRM 978a standard, sediment CRM PACS-2, domestic sludge SRM 2781, industrial sludge 2782, and the fish liver CRM DOLT-4. The sediment CRM PACS-2 has a very small negative delta(107/109)Ag value of -0.025 +/- 0.012 per thousand (2SD, n = 4). The domestic sludge SRM 2781 has a negative delta(107/109)Ag value of -0.061 +/- 0.010 per thousand (2SD, n = 4), whereas industrial sludge SRM 2782 has a positive delta(107/109)Ag value of +0.044 +/- 0.014 per thousand (2SD, n = 4), which may indicate the contribution of Ag from different anthropogenic inputs. DOLT-4 has a much larger negative value of -0.284 +/- 0.014 per thousand (2SD, n = 4), possibly caused by biological processes. These observations confirm that Ag isotope fractionation may provide a useful tool for fingerprinting sources of Ag in the environment and for studying a wide variety of chemical and biological processes in nature. High precision of better than +/-0.015 per thousand (2SD, n = 4) obtained in real sample matrixes makes the present method well suited for monitoring small Ag isotope fractionation in nature. PMID- 20361771 TI - DFT calculations of indirect 29Si-1H spin-spin coupling constants in organoalkoxysilanes. AB - The performance of four basis sets (6-311+G(2d,p), IGLO-III, cc-PVTZ, and 6-31G) is evaluated in order to find a quantum mechanical technique that can be used to accurately estimate (29)Si-(1)H spin-spin coupling constants in organoalkoxysilanes. The 6-31G basis set with the B3LYP functional is found to be an accurate, efficient, and cost-effective density functional theory method for predicting spin-spin coupling constants of organoalkoxysilanes. Knowledge of these scalar coupling constants and their dependence on structural variations is important to be able to fine-tune NMR experiments that rely on polarization transfer among nuclei, such as (29)Si distortionless enhancement by polarization transfer (DEPT). The effects of size and the number of unhydrolyzable alkyl groups attached to silicon and the effects of substitution of alkoxy groups with hydroxyl groups on (29)Si-(1)H spin-spin coupling constants are investigated using this DFT method. The results show that the predicted scalar coupling between silicon and organic groups depends weakly on the degree of hydrolysis of the alkoxysilanes. The effectiveness of this method is also illustrated for the determination of spin-spin coupling constants in a species containing a siloxane bond. PMID- 20361772 TI - Quantitative high-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis of bis-N7-guanine DNA-DNA cross-links in white blood cells of cancer patients receiving cyclophosphamide therapy. AB - Cyclophosphamide (CPA) is a DNA alkylating agent widely used in cancer chemotherapy. CPA undergoes metabolic activation to phosphoramide mustard and nornitrogen mustard (NOR) which alkylate the N-7 position of guanine in DNA to produce N-[2-(N7-guaninyl) ethyl]-N-[2-hydroxyethyl]-amine (G-NOR-OH) monoadducts and N,N-bis[2-(N7-guaninyl) ethyl] amine cross-links (G-NOR-G). G-NOR-G cross links are strongly cytotoxic and are thought to be responsible for the biological activity of CPA. In the present work, an isotope dilution high-performance liquid chromatography-electrospray ionization (positive ion) tandem mass spectrometry (HPLC-ESI(+)-MS/MS) methodology was developed to accurately quantify G-NOR-G adducts in human blood. In our approach, DNA extracted from white blood cells (5 20 microg) is spiked with an internal standard of [(15)N(10)]-G-NOR-G and subjected to thermal hydrolysis to release G-NOR-G adducts from the DNA backbone. Following solid phase extraction, G-NOR-G conjugates are quantified by capillary HPLC-ESI-MS/MS in the selected reaction monitoring mode. The application of the new methodology is demonstrated for DNA extracted from blood of three cancer patients receiving 50-60 mg/kg of intravenous CPA. The highest numbers of G-NOR-G adduct (up to 18 adducts per 10(6) normal nucleotides) were observed 4-8 h following CPA administration, followed by a gradual decrease over time, probably due to adduct hydrolysis, DNA repair, and white blood cell death. This methodology will be useful for future investigations of the interindividual differences for CPA-induced DNA-DNA cross-linking. PMID- 20361773 TI - Metadynamics as a tool for mapping the conformational and free-energy space of peptides--the alanine dipeptide case study. AB - There is a need for a fast, accurate, and reliable method of sampling the conformational space of peptides and proteins in order to obtain a balanced free energy profile which can lead to our understanding of protein structure. We have utilized metadynamics for the conformational study of the solvated alanine dipeptide molecule, and our results show that the method has proven to be competent as a fast, robust, and reliable method for the conformation free-energy calculations of peptides in an explicit solvent, surpassing traditional methods such as umbrella sampling. We have also addressed the issue of the influence of different water models on the resulting free-energy profile in order to consistently decompose the setting of our simulation. All of the explicit water models for the simulation of biomolecules TIP3P, TIP4P, TIP4P/Ew, TIP5P, and SPCE have exhibited similar effects on the conformational preferences of alanine dipeptide with no significant differences. On the other hand, by comparing the potential energy surface in the gas phase and the free-energy surface in a water environment, we have shown that the interaction with water molecules is one of the most important structure-driving elements, with a great influence on the free energy surface (FES) of the solvated peptide and the conformational preferences of the peptide backbone. All of the tested force fields (ff03, ff99SB, opls-aa, and charmm27) appreciably differ in the population of the individual conformers and the barriers between them. Significant divergence was found on both the potential energy surface (PES) as well as free-energy surface (FES) calculated by charmm27. We have therefore concluded that the differences originate dominantly from the parametrization of the peptide backbone in the given force field rather than from a noncovalent interaction with water molecules. PMID- 20361774 TI - Facile approach to patterned binary polymer brush through photolithography and surface-initiated photopolymerization. AB - Taking advantage of the photobleaching and co-initiating properties of the dendritic thioxanthone (TX) photoinitiator, we developed a general and facile approach to fabricate patterned binary polymer brushes by combining photolithography and surface-initiated photopolymerization (SIPP). The dendritic TX photoinitiator monolayer was immobilized covalently on a silicon slide surface, followed by photobleaching through a mask. The resulting slides could initiate photopolymerization of methyl methacrylate (MMA) to generate a patterned poly (methyl methacrylate) (PMMA) brush, and subsequently initiate styrene (St) in the presence of TX to obtain patterned binary poly (methyl methacrylate) polystyrene (PMMA-PS) brushes. This general and facile method could be of use in large-scale patterned binary polymer brush fabrication. PMID- 20361775 TI - Coupling surface-enhanced resonance Raman scattering and electronic tongue as characterization tools to investigate biological membrane mimetic systems. AB - The surface-enhanced Raman scattering (SERS) effect and sensor and biosensor analyses are widely applied to investigate drug-biomolecule interactions or to detect trace amount of analytes. In this work, surface-enhanced resonance Raman scattering (SERRS) and an electronic tongue system using impedance spectroscopy were brought together, combining sensitivity and structural level information. Taking advantage of the use of layer-by-layer (LbL) films of phospholipids as biological membrane mimetic systems, cardiolipin (CLP) and dipalmitoyl phosphatidyl glycerol (DPPG) were applied as transducers onto Pt interdigitated electrodes forming an array of sensing units. This e-tongue system was able to detect the phenothiazine methylene blue (MB) below nanomolar concentrations. SERRS was applied to investigate the MB molecular arrangement (monomers or aggregates) when in contact with the phospholipids at trace levels of concentration. The key point was the adsorption of Ag nanoparticles (AgNPs) within the phospholipid LbL films. This approach did not compromise the e-tongue performance and allowed the recording of in situ SERRS spectra for the LbL films after immersion into MB aqueous solutions. The detection of MB through SERRS gave similar results to those reported in the literature but now with an unprecedented sensitivity. PMID- 20361776 TI - QM/MM (ONIOM) study of glycerol binding and hydrogen abstraction by the coenzyme B12-independent dehydratase. AB - Glycerol binding and the radical-initiated hydrogen transfer by the coenzyme B(12)-independent glycerol dehydratase from Clostridium butyricum were investigated by using quantum mechanical/molecular mechanical (QM/MM) calculations based on the high-resolution crystal structure (PDB code: 1r9d). Our QM/MM calculations of enzyme catalysis considered the electrostatic coupling between the quantum-mechanical and molecular-mechanical subsystems and two alternative mechanisms. In addition to performing QM/MM calculations in the enzyme, we evaluated energetics along the same reaction pathway in aqueous solution modeled by the polarized dielectric and in the virtual enzyme site that included full steric component from the enzyme residues described by molecular mechanics but lacked the electrostatic contribution of these residues. In this way, we established significant enzyme catalytic effect with respect to reference reactions in both an aqueous solution and a nonpolar cavity. Structurally, four hydrogen bonds formed between glycerol and H164, S282, E435, and D447 anchor glycerol for hydrogen abstraction by thiyl radical on C433. These hydrogen-bond partners orient glycerol molecule to facilitate the formation of the transition state for hydrogen abstraction from carbon C1. This reaction then proceeds with the activation free energy of 6.3 kcal/mol and the reaction free energy of 6.1 kcal/mol. The polarization effects imposed by these hydrogen bonds represent a predominant contribution to a 7.5 kcal/mol enzyme catalytic effect. These results demonstrate the importance of electrostatic catalysis and hydrogen-bonding in enzyme-catalyzed radical reactions and advance our understanding of the catalytic mechanism of B(12)-independent glycerol dehydratases. PMID- 20361777 TI - Manipulation of electron beam propagation by hetero-dimensional graphene junctions. AB - We demonstrate theoretically a new mechanism for the energy-selective manipulation of electron beam by nanostructured heterodimensional graphene junctions (HDGJs). Beam splitting, collimation, and beam-guide can all be realized by designing HDGJs of different dimensionality, size and orientation. Importantly, these different functions can be combined together by predesigned patterning of multiple HDGJ units in one graphene sheet, making it feasible for large-scale integration of quantum devices. Based on transport simulations, we further suggest an method to map out the electron beam propagation path through HDGJs by scanning probe microscopy. PMID- 20361778 TI - Synthesis of In2O3 nanowire-decorated Ga2O3 nanobelt heterostructures and their electrical and field-emission properties. AB - We report on the synthesis of In2O3 nanowire-decorated Ga2O3 nanobelt heterostructures via a simple catalyst-free method. A typical heterostructure, where an In2O3 nanowire forms a sort of a "dorsal fin" on the Ga2O3 nanobelt, exhibits the T-shaped cross-section. The structure, electrical porperties, and field-emission properties of this material are systematically investigated. The heterostructures possess a typical n-type semiconducting behavior with enhanced conductivity. Field-emission measurements show that they have a low turn-on field (approximately 1.31 V/microm) and a high field-enhancement factor (over 4000). The excellent field-emission characteristics are attributed to their special geometry and good electrical properties. The present In2O3-decorated Ga2O3 heterostructures are envisaged to be decent field-emitters useful in advanced electronic and optoelectronic nanodevices. PMID- 20361779 TI - Sterols and terpenoids from Melia azedarach. AB - Three new sterols (1-3) including an unprecedented ring A-seco natural product (1), five new terpenoids (4-8), and 15 known compounds were isolated from the bark of Melia azedarach. Their structures were elucidated by means of spectroscopic data, and the structure of 1 was confirmed by X-ray crystallography. PMID- 20361780 TI - Rapid structural identification of cytotoxic bufadienolide sulfates in toad venom from Bufo melanosticus by LC-DAD-MS(n) and LC-SPE-NMR. AB - Toad venom, namely, "Chansu" in China, has been widely used for the treatment of heart failure, sores, pains, and various cancers. Upon LC-MS analysis of the venom from Bufo melanosticus collected in Indonesia, new bufadienolide sulfates were identified. For a complete characterization, the MeOH extract of the toad venom from B. melanosticus was fractionated by preparative HPLC, and the structures of five new buadienolide sulfates (1-5) along with one new bufogenin (6) were rapidly elucidated on the basis of LC-DAD-MS(n) and LC-SPE-NMR data. The in vitro growth inhibitory activity of these six compounds along with hellebrin (positive control) has been assayed by means of the MTT colorimetric assay in four human and two mouse cancer cell lines. Compound 3 and hellebrin displayed similar and marked in vitro cytotoxicity. PMID- 20361781 TI - Size-dependent nanoscale kirkendall effect during the oxidation of nickel nanoparticles. AB - The transformation of Ni nanoparticles (NPs) of different sizes (average diameters of 9, 26, and 96 nm) during oxidation to hollow (single void) or porous (multiple voids) NiO through the nanoscale Kirkendall effect was observed by transmission electron microscopy. Samples treated for 1-4 h at 200-500 degrees C show that the structures of the completely oxidized NPs do not depend on the temperature, but oxidation proceeds more quickly at elevated temperatures. For the Ni/NiO system, after formation of an initial NiO shell (of thickness approximately 3 nm), single or multiple voids nucleate on the inner surface of the NiO shell, and the voids grow until conversion to NiO is complete. Differences in the void formation and growth processes cause size-dependent nanostructural evolution: For 9 and 26 nm NPs, a single void forms beneath the NiO shell, and the void grows by moving across the NP while conversion to NiO occurs opposite the site where the void initially formed. Because of the differences in the Ni/NiO volume ratios for the 9 and 26 nm NPs when the void first forms, they have distinct nanostructures: The 9 nm NPs form NiO shells that are nearly radially symmetric, while there is a pronounced asymmetry in the NiO shells for 26 nm NPs. By choosing an intermediate oxidation temperature and varying the reaction time, partially oxidized Ni(core)/NiO(shell) NPs can be synthesized with good control. For 96 nm NPs, multiple voids form and grow, which results in porous NiO NPs. PMID- 20361782 TI - Molecular basis of coupled protein and electron transfer dynamics of cytochrome c in biomimetic complexes. AB - Direct electron transfer (ET) of redox proteins immobilized on biomimetic or biocompatible electrodes represents an active field of fundamental and applied research. In this context, several groups have reported for a variety of proteins unexpected distance dependencies of the ET rate, whose origin remains largely speculative and controversial, but appears to be a quite general phenomenon. Here we have employed molecular dynamics (MD) simulations and electron pathway analyses to study the ET properties of cytochrome c (Cyt) electrostatically immobilized on Au coated by carboxyl-terminated alkylthiols. The MD simulations and concomitant binding energy calculations allow identification of preferred binding configurations of the oxidized and reduced Cyt which are established via different lysine residues and, thus, correspond to different orientations and dipole moments. Calculations of the electronic coupling matrices for the various Cyt/self-assembled monolayer (SAM) complexes indicate that the thermodynamically preferred protein orientations do not coincide with the orientations of optimum coupling. These findings demonstrate that the ET of the immobilized Cyt is controlled by an interplay between protein dynamics and tunneling probabilities. Protein dynamics exerts two level of tuning on the electronic coupling via reorientation (coarse) and low amplitude thermal fluctuations (fine). Upon operating the Au support as an electrode, electric-field-dependent alignment of the protein dipole moment becomes an additional determinant for the protein dynamics and thus for the overall ET rate. The present results provide a consistent molecular description of previous (spectro)electrochemical data and allow conclusions concerning the coupling of protein dynamics and ET of Cyt in physiological complexes. PMID- 20361783 TI - Quantification of thin film crystallographic orientation using X-ray diffraction with an area detector. AB - As thin films become increasingly popular (for solar cells, LEDs, microelectronics, batteries), quantitative morphological and crystallographic information is needed to predict and optimize the film's electrical, optical, and mechanical properties. This quantification can be obtained quickly and easily with X-ray diffraction using an area detector in two sample geometries. In this paper, we describe a methodology for constructing complete pole figures for thin films with fiber texture (isotropic in-plane orientation). We demonstrate this technique on semicrystalline polymer films, self-assembled nanoparticle semiconductor films, and randomly packed metallic nanoparticle films. This method can be immediately implemented to help understand the relationship between film processing and microstructure, enabling the development of better and less expensive electronic and optoelectronic devices. PMID- 20361784 TI - Molecular scaffolds with high propensity to form multi-target activity cliffs. AB - In target-dependent activity landscapes of compound series, cliffs are formed by pairs of molecules that are structurally analogous but display significant differences in potency. The detection and analysis of such activity cliffs is a major task in structure-activity relationship analysis and compound optimization. In analogy to activity cliffs, selectivity cliffs can be defined that are formed by structural analogs having significantly different potencies against two targets. The formation of activity cliffs by analogs is generally a consequence of different R-group patterns; e.g., a specific substitution of a given scaffold might increase and another substitution decrease potency. Therefore, activity (or selectivity) cliffs are typically analyzed for a given scaffold representing an analog series, and it has thus far not been explored whether certain scaffolds might display a general tendency to yield compounds forming activity cliffs against different targets. We have exhaustively analyzed scaffolds and associated compound activity data in the ChemblDB and BindingDB databases in order to compare the availability of target-selective scaffolds in these databases and determine whether multi-target activity and multi-target selectivity cliff scaffolds exist. Perhaps unexpectedly, we have identified 143 scaffolds that are represented by multiple compounds and form activity or selectivity cliffs against different targets. These scaffolds have varying chemical complexities and are in part promiscuous binders (i.e., compounds containing these scaffolds bind to distantly related or unrelated targets). However, analogs derived from these scaffolds form steep activity cliffs against different targets. A catalog of scaffolds with high propensity to form activity or selectivity cliffs against multiple targets is provided to help identify potentially promiscuous candidate scaffolds during compound optimization efforts. PMID- 20361785 TI - A comparative study of multivariate and univariate hidden Markov modelings in time-binned single-molecule FRET data analysis. AB - We compare two different types of hidden Markov modeling (HMM) algorithms, e.g., multivariate HMM (MHMM) and univariate HMM (UHMM), for the analysis of time binned single-molecule fluorescence energy transfer (smFRET) data. In MHMM, the original two channel signals, i.e., the donor fluorescence intensity (I(D)) and acceptor fluorescence intensity (I(A)), are simultaneously analyzed. However, in UHMM, only the calculated FRET trajectory is analyzed. On the basis of the analysis of both synthetic and experimental data, we find that, if the noise in the signal is described with a proper probability distribution, MHMM generally outperforms UHMM. We also show that, in the case of multiple trajectories, analyzing them simultaneously gives better results than averaging over individual analysis results. PMID- 20361786 TI - Nanostructure to microstructure self-assembly of aliphatic polyurethanes: the effect on mechanical properties. AB - We report the step by step self-assembly from nanostructure to microstructure (bottom-up approach through X-ray diffraction (1.6 nm), small angle neutron scattering (SANS) (11.6 nm), atomic force microscopy (70 nm smaller crystallite from enlarged image and 450 nm greater crystallites), and polarizing optical microscope (2 microm)) of aliphatic polyurethanes (PU) in contrast to aromatic polyurethanes depending on hard segment content (HSC). Polyurethanes of 10 to 80% HSC have been synthesized by using appropriate amount of polyol and chain extender. The effect of self-assembled patterns on mechanical properties both in solid and liquid state has been established exhibiting structure-property relationship of supramolecular polyurethanes. The crystallinity enhances but the degradation temperature decreases with increasing HSC. The characteristic length (measure of gap between lamellar crystallites), as revealed from SANS, gradually decreases with increasing HSC suggesting compactness of the crystallites through extensive hydrogen bonding. The Young's modulus increases with increasing HSC with a percolation threshold of hard segment (50%) while the toughness improves up to 30% HSC followed by gradual decrease in presence of bigger crystallites which promote brittle fracture. The origin of self-assembly in aliphatic PUs has been demonstrated through electronic structure calculations to form a loop structure with minimum intermolecular distance (2.2 A) while that distance is quite large in aromatic polyurethanes (4.6 A) that cannot form hydrogen bonds. The unique splintering of domain structure and its subsequent reformation under dynamic shear experiment has been established. PMID- 20361788 TI - Rates and equilibria for probe capture by an antibody with infinite affinity. AB - Probe-capture systems based on proteins and synthetic ligands have become important for new analytical and imaging applications. We have used kinetic measurements of luminescence and measurements of binding by isothermal calorimetry to determine essential rate and equilibrium constants for a system that permanently captures modified DOTA chelates for positron imaging. We used that information along with previous results to quantitatively characterize the behavior of this system in vitro and in vivo. Under physiological conditions at 37 degrees C, the equilibrium dissociation constant for yttrium S-2-(4 aminobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetate from antibody 2D12.5 is 2.0 (+/- 0.4) x 10(-9) M and the dissociation rate constant is 7.0 (+/- 0.7) x 10(-3) s(-1), leading to an inferred association rate constant of 3.5 x 10(6) M( 1) s(-1). Using these values to interpret data from earlier experiments leads to the rate constant 2.5 x 10(-2) s(-1) for covalent attachment of bound yttrium S-2 (4-acrylamidobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetate to the G54C mutant of antibody 2D12.5. These values lead to a model for the detailed behavior of the latter system for tumor imaging in vivo that is consistent with experimental observations. PMID- 20361787 TI - A palette of fluorescent probes with varying emission colors for imaging hydrogen peroxide signaling in living cells. AB - We present a new family of fluorescent probes with varying emission colors for selectively imaging hydrogen peroxide (H(2)O(2)) generated at physiological cell signaling levels. This structurally homologous series of fluorescein- and rhodol based reporters relies on a chemospecific boronate-to-phenol switch to respond to H(2)O(2) over a panel of biologically relevant reactive oxygen species (ROS) with tunable excitation and emission maxima and sensitivity to endogenously produced H(2)O(2) signals, as shown by studies in RAW264.7 macrophages during the phagocytic respiratory burst and A431 cells in response to EGF stimulation. We further demonstrate the utility of these reagents in multicolor imaging experiments by using one of the new H(2)O(2)-specific probes, Peroxy Orange 1 (PO1), in conjunction with the green-fluorescent highly reactive oxygen species (hROS) probe, APF. This dual-probe approach allows for selective discrimination between changes in H(2)O(2) and hypochlorous acid (HOCl) levels in live RAW264.7 macrophages. Moreover, when macrophages labeled with both PO1 and APF were stimulated to induce an immune response, we discovered three distinct types of phagosomes: those that generated mainly hROS, those that produced mainly H(2)O(2), and those that possessed both types of ROS. The ability to monitor multiple ROS fluxes simultaneously using a palette of different colored fluorescent probes opens new opportunities to disentangle the complex contributions of oxidation biology to living systems by molecular imaging. PMID- 20361789 TI - Multifrequency electron spin resonance study of the dynamics of spin labeled T4 lysozyme. AB - An extensive set of electron spin resonance spectra was obtained over a wide range of frequencies (9, 95, 170, and 240 GHz) and temperatures (2 to 32 degrees C) to explore the dynamic modes of nitroxide-labeled T4 lysozyme in solution. A commonly used nitroxide side chain (R1), or a methylated analogue with hindered internal motion (R2), was substituted for the native side chain at solvent exposed helical sites, 72 or 131. The spectra at all four frequencies were simultaneously fit with the slowly relaxing local structure (SRLS) model. Good fits were achieved at all the temperatures. Two principle dynamic modes are included in the SRLS model, the global tumbling of the protein and the internal motion consisting of backbone fluctuations and side chain isomerizations. Three distinct spectral components were required for R1 and two for R2 to account for the spectra at all temperatures. One is a highly ordered and slow motional component, which is observed in the spectra of both R1 and R2; it may correspond to conformers stabilized by interaction with the protein surface. The fraction of this component decreases with increasing temperature and is more populated in the R2 spectra, possibly arising from stronger interaction of the nitroxide ring with the protein surface due to the additional methyl group. The other two components of R1 and the second component of R2 are characterized by fast anisotropic diffusion and relatively low ordering, most likely corresponding to conformers having little or no interactions with nearby residues. Ficoll of different concentrations was added to increase the solution viscosity, thereby slowing down the global tumbling of the protein. A significant effect of Ficoll on the internal motion of an immobilized component was apparent in R2 but not in R1. The ability of such multifrequency studies to separate the effects of faster internal modes of motion from slower overall motions is clearly demonstrated, and its utility in future studies is considered. PMID- 20361790 TI - PETN ignition experiments and models. AB - Ignition experiments from various sources, including our own laboratory, have been used to develop a simple ignition model for pentaerythritol tetranitrate (PETN). The experiments consist of differential thermal analysis, thermogravimetric analysis, differential scanning calorimetry, beaker tests, one dimensional time to explosion tests, Sandia's instrumented thermal ignition tests (SITI), and thermal ignition of nonelectrical detonators. The model developed using this data consists of a one-step, first-order, pressure-independent mechanism used to predict pressure, temperature, and time to ignition for various configurations. The model was used to assess the state of the degraded PETN at the onset of ignition. We propose that cookoff violence for PETN can be correlated with the extent of reaction at the onset of ignition. This hypothesis was tested by evaluating metal deformation produced from detonators encased in copper as well as comparing postignition photos of the SITI experiments. PMID- 20361791 TI - Crystal structures of the glycopeptide sulfotransferase Teg12 in a complex with the teicoplanin aglycone. AB - The TEG gene cluster, a glycopeptide biosynthetic gene cluster that is predicted to encode the biosynthesis of a polysulfated glycopeptide congener, was recently cloned from DNA extracted directly from desert soil. This predicted glycopeptide gene cluster contains three closely related sulfotransferases (Teg12, -13, and 14) that sulfate teicoplanin-like glycopeptides at three unique sites. Here we report a series of structures: an apo structure of Teg12, Teg12 bound to the desulfated cosubstrate 3'-phosphoadenosine 5'-phosphate, and Teg12 bound to the teicoplanin aglycone. Teg12 appears to undergo a series of significant conformational rearrangements during glycopeptide recruitment, binding, and catalysis. Loop regions that exhibit the most conformational flexibility show the least sequence conservation between TEG sulfotransferases. Site-directed mutagenesis guided by our structural studies confirmed the importance of key catalytic residues as well as the importance of residues found throughout the conformationally flexible loop regions. PMID- 20361792 TI - Computer simulations on aggregation of acetic acid in the gas phase, liquid phase, and supercritical carbon dioxide. AB - Computer simulations including semiempirical molecular orbital and Monte Carlo methods were employed to investigate the aggregation of acetic acid in the gas phase, liquid phase, and supercritical carbon dioxide. The binary vapor-liquid coexistence curves of the CO(2)/acetic acid mixtures were calculated at 313.2, 333.2, and 353.2 K and are in excellent agreement with experimental measurements. Two sets of rigorous hydrogen-bonding criteria were established for the hydrogen bonding at the hydroxyl oxygen and carbonyl oxygen, respectively. With the criteria, detailed statistics of hydrogen bonding states and distribution of aggregate sizes and structures were fully investigated and compared in the three phases, which will shed light on the development of more rigorous and accurate real associated solution models in the future. PMID- 20361793 TI - Fast and high-yield microreactor syntheses of ortho-substituted [(18)F]fluoroarenes from reactions of [(18)F]fluoride ion with diaryliodonium salts. AB - A microreactor was applied to produce ortho-substituted [(18)F]fluoroarenes from the reactions of cyclotron-produced [(18)F]fluoride ion (t(1/2) = 109.7 min) with diaryliodonium salts. The microreactor provided a very convenient means for running sequential reactions rapidly with small amounts of reagents under well controlled conditions, thereby allowing reaction kinetics to be followed and Arrhenius activation energies (E(a)) to be measured. Prepared symmetrical iodonium chlorides (Ar(2)I(+)Cl(-)) rapidly (<4 min) gave moderate (Ar = 2 MeOC(6)H(4), 51%) to high (Ar = Ph or 2-MeC(6)H(4), 85%) decay-corrected radiochemical yields (RCYs) of a single radioactive product (Ar(18)F). Reaction velocity with respect to Ar group was 2-MeOC(6)H(4) < Ph < 2-MeC(6)H(4). Activation energies were in the range 18-28 kcal/mol. Prepared unsymmetrical salts (e.g., 2-RC(6)H(4)I(+)2'-R'C(6)H(4)X(-); X = Cl or OTs) also rapidly gave two products (2-RC(6)H(4)(18)F and 2-R'C(6)H(4)(18)F) in generally high total RCYs (79-93%). Selectivity for product [(18)F]fluoroarene was controlled by the nature of the ortho substituents. The power of ortho substituents to impart an ortho-effect was in the following order:, 2,6-di-Me > 2,4,6-tri-Me > Br > Me > Et approximately (i)Pr >> H > OMe. For (2-methyphenyl)(phenyl)iodonium chloride, the time-course of reaction product selectivity was constant and consistent with the operation of the Curtin-Hammett principle. These results will aid in the design of diaryliodonium salt precursors to (18)F-labeled tracers for molecular imaging. PMID- 20361794 TI - Chiral phosphoric acid catalyzed addition of dihydropyrans to N-acyl imines: stereocontrolled access to enantioenriched spirocyclic oxazoletetrahydropyrans with three contiguous stereocenters. AB - Dihydropyran derivatives readily undergo addition to N-acyl imines in the presence of chiral phosphoric acids. This addition process yields an attractive product that is capable of a tandem oxidative-cyclization via an epoxide intermediate. PMID- 20361795 TI - A simple method of separating metallic and semiconducting single-walled carbon nanotubes based on molecular charge transfer. AB - Interaction of as-prepared single-walled carbon nanotubes (SWNTs), containing a mixture of metallic and semiconducting species with the potassium salt of coronene tetracarboxylic acid, I, in an aqueous medium provides a simple method of separating semiconducting and metallic species. The metallic nanotubes precipitate out on interaction with I while the semiconducting nanotubes remain in solution. The method avoids centrifugation and is amenable for large-scale separation and can be used as a routine laboratory procedure. Interestingly, interaction with strong electron acceptor molecules brings about metal semiconductor transitions in SWNTs. PMID- 20361796 TI - Design of an encodable tyrosine kinase-inducible domain: detection of tyrosine kinase activity by terbium luminescence. AB - Tyrosine kinases are critical mediators of intracellular signaling and of intracellular responses to extracellular signaling. Changes in tyrosine kinase activity are implicated in numerous human diseases, including cancers, diabetes, and pathogen infectivity. To address questions in tyrosine phosphorylation, we have designed a protein tyrosine kinase-inducible domain, a small, genetically encodable protein motif whose structure is dependent on its tyrosine phosphorylation state. Tyrosine kinase-inducible domain peptides are based on EF hand loops in which a structurally critical Glu12 residue is replaced by tyrosine at residue 11 or at residue 15 of the protein. Tyrosine kinase-inducible domain peptides bind terbium(III) in a phosphorylation-dependent manner, showing strong terbium luminescence when phosphorylated but weak terbium luminescence when not phosphorylated. Lanthanide binding was confirmed by NMR. A tyrosine kinase inducible domain peptide, pKID-Abl, was designed to incorporate a recognition sequence of the Abl kinase. Incubation of pKID-Abl with Abl kinase resulted in a large increase in terbium luminescence. This increase in luminescence was abolished when pKID-Abl and Abl kinase were incubated with the Abl kinase inhibitor Gleevec. In addition, incubation of phosphorylated pKID-Abl with the tyrosine phosphatase YOP resulted in a large reduction in terbium luminescence. pKID-Abl was employed as a fluorescent sensor of Abl tyrosine kinase activity in HeLa cell extracts, exhibiting low luminescence with extracts from serum-starved cells and increased luminescence using extracts from EGF-treated cells. These results indicate that tyrosine kinase-inducible domains may be used as sensors of tyrosine kinase and tyrosine phosphatase activity and in the detection of tyrosine kinase inhibitors. PMID- 20361797 TI - Automated chemical crystallography. AB - The first fully automated small-molecule robotic X-ray diffractometer is described. After demonstrating the utility of the instrument using multiple samples of ammonium bitartrate, we investigated the conformational chirality of diphenyl dichalcogenide (E(2)Ph(2), where E = S, Se, or Te). Structural and computational studies suggest that the two enantiomers are energetically indistinguishable. Therefore, it was unsurprising that we found (in 35 suitable data collections) the proportion 0.51:0.49 of M-S(2)Ph(2) to P-S(2)Ph(2) in the bulk sample. Interestingly, after 65 data collections of Te(2)Ph(2), (46 provided suitable data sets), we found the proportion 0.72 +/- 0.13 of M-Te(2)Ph(2), suggesting there could be a statistically significant preference for the M enantiomer in the sample examined here. We found that Se(2)Ph(2) underwent homochiral crystallization, with all 24 crystals being M. Our experiments may represent a salutary lesson in statistical analysis. PMID- 20361798 TI - A small-molecule-based ternary data-storage device. AB - High-density data storage (HDDS) is urgently required to address ongoing rapid increases in amounts of information. Here we present a prototype sandwich device that has ternary data-storage performance. Three characteristic currents can be read out using a certain constant voltage after removal of the applied voltage. Two electron pull groups and one electron push group are identified as the species responsible for electron flow. We believe that our observation will offer an interesting and useful theoretical approach for a huge increase in the memory density of potential future devices. PMID- 20361799 TI - Development of a new generation of 4-aminoquinoline antimalarial compounds using predictive pharmacokinetic and toxicology models. AB - Among the known antimalarial drugs, chloroquine (CQ) and other 4-aminoquinolines have shown high potency and good bioavailability. Yet complications associated with drug resistance necessitate the discovery of effective new antimalarial agents. ADMET prediction studies were employed to evaluate a library of new molecules based on the 4-aminoquinolone-related structure of CQ. Extensive in vitro screening and in vivo pharmacokinetic studies in mice helped to identify two lead molecules, 18 and 4, with promising in vitro therapeutic efficacy, improved ADMET properties, low risk for drug-drug interactions, and desirable pharmacokinetic profiles. Both 18 and 4 are highly potent antimalarial compounds, with IC(50) values of 5.6 and 17.3 nM, respectively, against the W2 (CQ resistant) strain of Plasmodium falciparum (for CQ, IC(50) = 382 nM). When tested in mice, these compounds were found to have biological half-lives and plasma exposure values similar to or higher than those of CQ; they are therefore desirable candidates to pursue in future clinical trials. PMID- 20361800 TI - 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. AB - To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3'-oxime derivatives with combined substitutions at the 5 and 5' positions. A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5' position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Among the synthesized derivatives, the 5-nitro-5' hydroxy analogue 3a and the 5-nitro-5'-fluoro analogue 5a displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. These derivatives also showed antiproliferative activity against several human cancer cell lines, with IC(50) values of 0.2-3.3 microM. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity. PMID- 20361801 TI - Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. AB - Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with multifactorial causes that requires multitargeted treatment. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) improve cholinergic signaling in the central nervous system and thus AChE inhibitors are well established in the therapy of AD to improve memory disturbances and other cognitive symptoms. On the other hand, AD patients benefit from reduction of pathologic glutamate-induced, Ca(2+)-mediated excitotoxicity by the N-methyl-d aspartate receptor (NR) antagonist memantine. New drugs that simultaneously affect both cholinergic transmission and glutamate-induced excitotoxicity may further improve AD treatment. While connecting beta-carboline units by alkylene spacers in two different series of compounds and subsequent evaluation of their AChE/BChE-inhibitory potential, we found that several of these bivalent beta carbolines were potent NR blockers. The most promising compound was a N(9) homobivalent beta-carboline with a nonylene spacer, which displayed IC(50) values of 0.5 nM for AChE, 5.7 nM for BChE, and 1.4 microM for NR, respectively. PMID- 20361802 TI - Sulfonylation-induced N- to O-acetyl migration in 2-acetamidoethanol derivatives. AB - The first example of sulfonylation-induced N- to O-acetyl migration of 2 acetamidoethanol derivatives is described. This type of reaction could happen with any 2-acetamidoethanol derivatives under typical sulfonylation conditions (TsCl or MsCl, pyridine) and might be a common side reaction of significance. Furthermore, the results reveal that 2-acetamidoethanol derivatives with a sterically encumbered hydroxyl group result in the migration products in high yields. The mechanism of the migration reaction is discussed. PMID- 20361804 TI - Some simple epidemic models. AB - The SARS epidemic of 2002-3 led to the study of epidemic models including management measures and other generalizations of the original 1927 epidemic model of Kermack and McKendrick. We consider some natural extensions of the Kermack McKendrick model and show that they share the main properties of the original model. PMID- 20361805 TI - Nonlinear semelparous leslie models. AB - In this paper we consider the bifurcations that occur at the trivial equilibrium of a general class of nonlinear Leslie matrix models for the dynamics of a structured population in which only the oldest class is reproductive. Using the inherent net reproductive number n as a parameter, we show that a global branch of positive equilibria bifurcates from the trivial equilibrium at n = 1 despite the fact that the bifurcation is nongeneric. The bifurcation can be either supercritical or subcritical, but unlike the case of a generic transcritical bifurcation in iteroparous models, the stability of the bifurcating positive equilibria is not determined by the direction of bifurcation. In addition we show that a branch of single-class cycles also bifurcates from the trivial equilibrium at n = 1. In the case of two population classes, either the bifurcating equilibria or the bifurcating cycles are stable (but not both) depending on the relative strengths of the inter- and intra-class competition. Strong inter-class competition leads to stable cycles in which the two population classes are temporally separated. In the case of three or more classes the bifurcating cycles often lie on a bifurcating invariant loop whose structure is that of a cycle chain consisting of the different phases of a periodic cycle connected by heteroclinic orbits. Under certain circumstances, these bifurcating loops are attractors. PMID- 20361803 TI - Use of hydromorphone, with particular reference to the OROS formulation, in the elderly. AB - The prevalence of pain increases with age. However, pain is often inadequately managed in elderly people, which undermines quality of life. Pain has been associated with depression, sleep disturbances, impaired ambulation, and increased healthcare use and costs. Effective treatment of pain improves the overall quality of life. However, pain management is complicated by the presence of multiple co-morbidities in elderly people, which increases the likelihood of polypharmacy, and therefore increases the chance of potential drug-drug interactions. Polypharmacy is also associated with poor adherence to therapy. Age related pharmacokinetic and pharmacodynamic changes reduce the therapeutic index of drugs. Therefore, elderly people are more likely to suffer from adverse events and increased sensitivity to the analgesic properties of opioids. OROS hydromorphone (Jurnista) is a once-daily, extended-release formulation that uses the OROS push-pull technology to provide controlled release of the semi-synthetic opioid hydromorphone. Compared with conventional immediate-release hydromorphone, OROS hydromorphone provides more consistent delivery of hydromorphone with lower peak concentrations and less variability in plasma concentrations over time. The bioavailability of hydromorphone from OROS hydromorphone is minimally affected by food or alcohol (ethanol). Hydromorphone is mainly metabolized in the liver and is excreted in the urine. Unlike morphine, hydromorphone does not have an active 6-glucuronide metabolite. This metabolite of morphine can accumulate in the presence of renal failure; therefore, the lack of an active 6-glucuronide metabolite makes hydromorphone a useful alternative to morphine in elderly patients with renal failure. However, hydromorphone is similar to morphine in that it is metabolized to hydromorphone-3-glucuronide, which may be neuroexcitatory. Because of its low plasma protein binding and low probability of interfering with the metabolism of other drugs, hydromorphone may be especially suitable for patients taking multiple medications. OROS hydromorphone is an effective analgesic that is well tolerated and provides more stable plasma concentrations than immediate-release forms of hydromorphone. Its once-daily administration offers an advantage over immediate-release forms and longer-acting formulations that require twice-daily administration. This means OROS hydromorphone will be more convenient for elderly patients and may improve adherence, resulting in improved pain relief and quality of life. PMID- 20361806 TI - An allelopathic competition model with quorum sensing and delayed toxicant production. AB - The dynamics of a differential functional equation system representing an allelopathic competition is analyzed. The delayed allelochemical production process is represented by means of a distributed delay term in a linear quorum sensing model. Sufficient conditions for local asymptotic stability properties of biologically meaningful steady-state solutions are given in terms of the parameters of the system. A global asymptotic stability result is also proved by constructing a suitable Lyapunov functional. Some simulations confirm the analytical results. PMID- 20361807 TI - Simulation of structured populations in chemically stressed environments. AB - A heterogenous environment usually impacts, and sometimes determines, the structure and function of organisms in a population. We simulate the effects of a chemical on a population in a spatially heterogeneous environment to determine perceived stressor and spatial effects on dynamic behavior of the population. The population is assumed to be physiologically structured and composed of individuals having both sessile and mobile life history stages, who utilize energetically-controlled, resource-directed, chemical-avoidance advective movements and are subjected to random or density dependent diffusion. From a modeling perspective, the presence of a chemical in the environment requires introduction of both an exposure model and an effects module. The spatial location of the chemical stressor determines the exposure levels and ultimately the effects on the population while the relative location of the resource and organism determines growth. We develop a mathematical model, the numerical analysis for this model, and the simulation techniques necessary to solve the problem of population dynamics in an environment where heterogeneity is generated by resource and chemical stressor. In the simulations, the chemical is assumed to be a nonpolar narcotic and the individuals respond to the chemical via both physiological response and by physical movement. In the absence of a chemical stressor, simulation experiments indicate that despite a propensity to move to regions of higher resource density, organisms need not concentrate in the vicinity of high levels of resource. We focus on the dynamical variations due to advection induced by the toxicant. It is demonstrated that the relationship between resource levels and toxicant concentrations is crucial in determining persistence or extinction of the population. PMID- 20361808 TI - Some bifurcation methods of finding limit cycles. AB - In this paper we outline some methods of finding limit cycles for planar autonomous systems with small parameter perturbations. Three ways of studying Hopf bifurcations and the method of Melnikov functions in studying Poincare bifurcations are introduced briefly. A new method of stability- changing in studying homoclinic bifurcation is described along with some interesting applications to polynomial systems. PMID- 20361809 TI - Weakly coupled traveling waves for a model of growth and competition in a flow reactor. AB - For a reaction-diffusion model of microbial flow reactor with two competing populations, we show the coexistence of weakly coupled traveling wave solutions in the sense that one organism undergoes a population growth while another organism remains in a very low population density in the first half interval of the space line; the population densities then exchange the position in the next half interval. This type of traveling wave can occur only if the input nutrient slightly exceeds the maximum carrying capacity for these two populations. This means, lacking an adequate nutrient, two competing organisms will manage to survive in a more economical way. PMID- 20361810 TI - Differential susceptibility and infectivity epidemic models. AB - We formulate differential susceptibility and differential infectivity models for disease transmission in this paper. The susceptibles are divided into n groups based on their susceptibilities, and the infectives are divided into m groups according to their infectivities. Both the standard incidence and the bilinear incidence are considered for different diseases. We obtain explicit formulas for the reproductive number. We define the reproductive number for each subgroup. Then the reproductive number for the entire population is a weighted average of those reproductive numbers for the subgroups. The formulas for the reproductive number are derived from the local stability of the infection-free equilibrium. We show that the infection-free equilibrium is globally stable as the reproductive number is less than one for the models with the bilinear incidence or with the standard incidence but no disease-induced death. We then show that if the reproductive number is greater than one, there exists a unique endemic equilibrium for these models. For the general cases of the models with the standard incidence and death, conditions are derived to ensure the uniqueness of the endemic equilibrium. We also provide numerical examples to demonstrate that the unique endemic equilibrium is asymptotically stable if it exists. PMID- 20361811 TI - The stability of an sir epidemic model with time delays. AB - In this paper, an SIR epidemic model for the spread of an infectious disease transmitted by direct contact among humans and vectors (mosquitoes ) which have an incubation time to become infectious is formulated. It is shown that a disease free equilibrium point is globally stable if no endemic equilibrium point exists. Further, the endemic equilibrium point (if it exists) is globally stable with respect to a "weak delay". Some known results are generalized. PMID- 20361812 TI - A competition model of the chemostat with an external inhibitor. AB - A competition model of the chemostat with an external inhibitor is considered. This inhibitor is lethal to one competitor and results in the decrease of growth rate of this competitor. The existence and stability of the extinction equilibria are discussed by using Liapunov function. The necessary and sufficient condition guaranteeing the existence of the interior equilibrium is given. It is found by numerical simulation that the system may be globally stable or have a stable limit cycle if the interior equilibrium exists. PMID- 20361813 TI - Travelling wave solutions for higher-order wave equations of kdv type (iii). AB - By using the theory of planar dynamical systems to the travelling wave equation of a higher order nonlinear wave equations of KdV type, the existence of smooth solitary wave, kink wave and anti-kink wave solutions and uncountably infinite many smooth and non-smooth periodic wave solutions are proved. In different regions of the parametric space, the sufficient conditions to guarantee the existence of the above solutions are given. In some conditions, exact explicit parametric representations of these waves are obtain. PMID- 20361814 TI - Permanence for two-species lotka-volterra systems with delays. AB - The permanence of the following Lotka-Volterra system with time delays x '(1) ( t ) = x(1) ( t ) [ r(1) - a(1)x(1) ( t ) + a(11)x(1) ( t - tau(11) ) + a(12)x(2) ( t - tau(12) ) ] x '(2) ( t ) = x(2) ( t ) [ r(2) - a(2)x(2) ( t ) + a(21)x(1) ( t - tau(21) ) + a(22)x(2) ( t - tau(22) ) ] is considered.With intraspecific competition, it is proved that in competitive case, the system is permanent if and only if the interaction matrix of the system satisfies condition (C1) and in cooperative case it is proved that condition (C2) is sufficient for the permanence of the system. PMID- 20361815 TI - Modeling spatial spread of west nile virus and impact of directional dispersal of birds. AB - A patchy model for the spatial spread of West Nile virus is formulated and analyzed. The basic reproduction number is calculated and com- pared for different long-range dispersal patterns of birds, and simulations are carried out to demonstrate discontinuous or jump spatial spread of the virus when the birds' long-range dispersal dominates the nearest neighborhood interaction and diffusion of mosquitoes and birds. PMID- 20361816 TI - Epidemic threshold conditions for seasonally forced seir models. AB - In this paper we derive threshold conditions for eradication of diseases that can be described by seasonally forced susceptible-exposed-infectious- recovered (SEIR) models or their variants. For autonomous models, the basic reproduction number R(0) < 1 is usually both necessary and sufficient for the extinction of diseases. For seasonally forced models, R(0) is a function of time t. We find that for models without recruitment of susceptible individuals (via births or loss of immunity), max(t) {R(0)(t)} < 1 is required to prevent outbreaks no matter when and how the disease is introduced. For models with recruitment, if the latent period can be neglected, the disease goes extinct if and only if the basic reproduction number R' of the time-average systems (the autonomous systems obtained by replacing the time-varying parameters with their long-term time averages) is less than 1. Otherwise, R' < 1 is sufficient but not necessary for extinction. Thus, reducing R' of the average system to less than 1 is sufficient to prevent or curtail the spread of an endemic disease. PMID- 20361817 TI - Stability, delay, and chaotic behavior in a lotka-volterra predator-prey system. AB - We consider the following Lotka-Volterra predator-prey system with two delays: x '( t ) = x ( t ) [ r(1) - ax ( t - tau(1) ) - by( t ) ] y '( t ) = y ( t ) [ - r(1) + cx ( t ) - dy( t - tau(2) ) ] ( E ) We show that a positive equilibrium of system ( E ) is globally asymptotically stable for small delays. Critical values of time delay through which system ( E ) undergoes a Hopf bifurcation are analytically determined. Some numerical simulations suggest an existence of subcritical Hopf bifurcation near the critical values of time delay. Further system (E) exhibits some chaotic behavior when tau(2) becomes large. PMID- 20361818 TI - A nonlinear l(2)-stability analysis for two-species population dynamics with dispersal. AB - The nonlinear L(2)-stability (instability) of the equilibrium states of two species population dynamics with dispersal is studied. The obtained results are based on (i) the rigorous reduction of the L(2)-nonlinear stability to the stability of the zero solution of a linear binary system of ODEs and (ii) the introduction of a particular Liapunov functional V such that the sign ofdV/dt along the solutions is linked directly to the eigenvalues of the linear problem. PMID- 20361819 TI - The effect of global travel on the spread of sars. AB - The goal of this paper is to study the global spread of SARS. We propose a multiregional compartmental model using medical geography theory (central place theory) and regarding each outbreak zone (such as Hong Kong, Singapore, Toronto, and Beijing) as one region. We then study the effect of the travel of individuals (especially the infected and exposed ones) between regions on the global spread of the disease. PMID- 20361820 TI - Competing species models with an infectious disease. AB - The frequency-dependent (standard) form of the incidence is used for the transmission dynamics of an infectious disease in a competing species model. In the global analysis of the SIS model with the birth rate independent of the population size, a modified reproduction number R(1) determines the asymptotic behavior, so that the disease dies out if R(1) 1. Because the disease-reduced reproduction and disease-related death rates are often different in two competing species, a shared disease can change the outcome of the competition. Models of SIR and SIRS type are also considered. A key result in all of these models with the frequency-dependent incidence is that the disease must either die out in both species or remain endemic in both species. PMID- 20361821 TI - An improved model of T cell development in the thymus and its stability analysis. AB - Based on some important experimental dates, in this paper we shall introduce time delays into Mehrs's non-linear differential system model which is used to describe proliferation, differentiation and death of T cells in the thymus (see, for example, [3], [6], [7] and [9]) and give a revised nonlinear differential system model with time delays. By using some classical analysis techniques of functional differential equations, we also consider local and global asymptotic stability of the equilibrium and the permanence of the model. PMID- 20361822 TI - Raves, clubs and ecstasy: the impact of peer pressure. AB - Ecstasy has gained popularity among young adults who frequent raves and nightclubs. The Drug Enforcement Administration reported a 500 percent increase in the use of ecstasy between 1993 and 1998. The number of ecstasy users kept growing until 2002, years after a national public education initiative against ecstasy use was launched. In this study, a system of differential equations is used to model the peer-driven dynamics of ecstasy use. It is found that backward bifurcations describe situations when sufficient peer pressure can cause an epidemic of ecstasy use. Furthermore, factors that have the greatest influence on ecstasy use as predicted by the model are highlighted. The effect of education is also explored, and the results of simulations are shown to illustrate some possible outcomes. PMID- 20361823 TI - Epidemic models with nonlinear infection forces. AB - Epidemic models with behavior changes are studied to consider effects of protection measures and intervention policies. It is found that intervention strategies decrease endemic levels and tend to make the dynamical behavior of a disease evolution simpler. For a saturated infection force, the model may admit a stable disease-free equilibrium and a stable endemic equilibrium at the same time. If we vary a recovery rate, numerical simulations show that the boundaries of the region for the persistence of the disease undergo the changes from the separatrix of a saddle to an unstable limit cycle. If the inhibition effect from behavior changes is weak, we find two limit cycles and obtain bifurcations of the model as the population size changes. We also find that the disease may die out although there are two endemic equilibria. PMID- 20361824 TI - Competition and dispersal delays in patchy environments. AB - Dispersal delays are introduced into a competition model for two species that disperse among n identical patches. The model is formulated as a system of integro-differential equations with an arbitrary distribution of dispersal times between patches. By identifying steady states and analyzing local stability, conditions for competitive exclusion, coexistence or extinction are determined in terms of the system parameters. These are confirmed by numerical simulations with a delta function distribution, showing that all solutions approach a steady state and that high dispersal is generally a disadvantage to a species. However, if the two species have identical local dynamics, then small dispersal rates (with certain parameter restrictions) can be an advantage to the dispersing species. If the number of species is increased to three, then oscillatory coexistence with dispersal delay is possible. PMID- 20361825 TI - The effects of vertical transmission on the spread of hiv/aids in the presence of treatment. AB - In this study, we develop a model that incorporates treatment of both juveniles who were infected with HIV/AIDS through vertical transmission and HIV/AIDS infected adults. We derive conditions under which the burden of HIV/AIDS can be reduced in the population both in the absence of and in the presence of vertical transmission. We have determined the critical threshold parameter (R(*)(v)), which represents the demographic replacement of infectives through vertical transmission, below which treated infected juveniles can reach adulthood without causing an epidemic. Five countries in sub-Saharan Africa are used to illustrate our results. We have concluded that R(*)(v) is dependent on the current prevalence rate but that a significant proportion of infected juveniles receiving treatment can reach adulthood without causing an epidemic. PMID- 20361826 TI - Modeling cancer in hiv-1 infected individuals: equilibria, cycles and chaotic behavior. AB - For HIV-infected individuals, cancer remains a significant burden. Gaining insight into the epidemiology and mechanisms that underlie AIDS- related cancers can provide us with a better understanding of cancer immunity and viral oncogenesis. In this paper, an HIV-1 dynamical model incorporat- ing the AIDS related cancer cells was studied. The model consists of three components, cancer cells, healthy CD4+ T lymphocytes and infected CD4+ T lymphocytes, and can have six steady states. We discuss the existence, the stability properties and the biological meanings of these steady states, in par- ticular for the positive one: cancer-HIV-healthy cells steady state. We find conditions for Hopf bifurcation of the positive steady state, leading to periodic solutions, sequences of period doubling bifurcations and appearance of chaos. Further, chaos and periodic behavior alternate. Our results are consistent with some clinical and experimental observations. PMID- 20361827 TI - Global asymptotic stability and hopf bifurcation for a blood cell production model. AB - We analyze the asymptotic stability of a nonlinear system of two differential equations with delay, describing the dynamics of blood cell produc- tion. This process takes place in the bone marrow, where stem cells differen- tiate throughout division in blood cells. Taking into account an explicit role of the total population of hematopoietic stem cells in the introduction of cells in cycle, we are led to study a characteristic equation with delay-dependent coefficients. We determine a necessary and sufficient condition for the global stability of the first steady state of our model, which describes the popula- tion's dying out, and we obtain the existence of a Hopf bifurcation for the only nontrivial positive steady state, leading to the existence of periodic solutions. These latter are related to dynamical diseases affecting blood cells known for their cyclic nature. PMID- 20361828 TI - Energy considerations in a model of nematode sperm crawling. AB - In this paper we propose a mathematical model for nematode sperm cell crawling. The model takes into account both force and energy balance in the process of lamellipodium protrusion and cell nucleus drag. It is shown that by specifying the (possibly variable) efficiency of the major sperm protein biomotor one completely determines a self-consistent problem of the lamellipodium-nucleus motion. The model thus obtained properly accounts for the feedback of the load on the lamellipodium protrusion, which in general should not be neglected. We study and analyze the steady crawling state for a particular efficiency function and find that all nonzero modes, up to a large magnitude, are linearly asymptotically stable, thus reproducing the experimental observations of the long periods of steady crawling exhibited by the nematode sperm cells. PMID- 20361829 TI - Simulation of pulsatile flow of blood in stenosed coronary artery bypass with graft. AB - In this paper, we investigate the behavior of the pulsatile blood flow in a stenosed right coronary artery with a bypass graft. The human blood is assumed to be a non-Newtonian fluid and its viscous behavior is described by the Carreau model. The transient phenomena of blood flow though the stenosed region and the bypass grafts are simulated by solving the three dimensional unsteady Navier Stokes equations and continuity equation. The influence of the bypass angle on the flow interaction between the jet flow from the native artery and the flow from the bypass graft is investigated. Distributions of velocity, pressure and wall shear stresses are determined under various conditions. The results show that blood pressure in the stenosed artery drops dramatically in the stenosis area and that high wall shear stresses occur around the stenosis site. PMID- 20361830 TI - Remark on the paper by rao and kakehashi (2005). PMID- 20361831 TI - Multiscale image registration. AB - A multiscale image registration technique is presented for the registration of medical images that contain significant levels of noise. An overview of the medical image registration problem is presented, and various registration techniques are discussed. Experiments using mean squares, normalized correlation, and mutual information optimal linear registration are presented that determine the noise levels at which registration using these techniques fails. Further experiments in which classical denoising algorithms are applied prior to registration are presented, and it is shown that registration fails in this case for significantly high levels of noise, as well. The hierarchical multiscale image decomposition of E. Tadmor, S. Nezzar, and L. Vese [20] is presented, and accurate registration of noisy images is achieved by obtaining a hierarchical multiscale decomposition of the images and registering the resulting components. This approach enables successful registration of images that contain noise levels well beyond the level at which ordinary optimal linear registration fails. Image registration experiments demonstrate the accuracy and efficiency of the multiscale registration technique, and for all noise levels, the multiscale technique is as accurate as or more accurate than ordinary registration techniques. PMID- 20361832 TI - Analysis of blood flow velocity and pressure signals using the multipulse method. AB - This paper shows how the multipulse method from digital signal processing can be used to accurately synthesize signals obtained from blood pressure and blood flow velocity sensors during posture change from sitting to standing. The multipulse method can be used to analyze signals that are composed of pulses of varying amplitudes. One of the advantages of the multipulse method is that it is able to produce an accurate and efficient representation of the signals at high resolution. The signals are represented as a set of input impulses passed through an autoregressive (AR) filter. The parameters that define the AR filter can be used to distinguish different conditions. In addition, the AR coefficients can be transformed to tube radii associated with digital wave guides, as well as pole zero representation. Analysis of the dynamics of the model parameters have potential to provide better insight and understanding of the underlying physiological control mechanisms. For example, our data indicate that the tube radii may be related to the diameter of the blood vessels. PMID- 20361833 TI - Visualisation of the numerical solution of partial differential equation systems in three space dimensions and its importance for mathematical models in biology. AB - Numerical analysis and computational simulation of partial differential equation models in mathematical biology are now an integral part of the research in this field. Increasingly we are seeing the development of partial differential equation models in more than one space dimension, and it is therefore necessary to generate a clear and effective visualisation platform between the mathematicians and biologists to communicate the results. The mathematical extension of models to three spatial dimensions from one or two is often a trivial task, whereas the visualisation of the results is more complicated. The scope of this paper is to apply the established marching cubes volume rendering technique to the study of solid tumour growth and invasion, and present an adaptation of the algorithm to speed up the surface rendering from numerical simulation data. As a specific example, in this paper we examine the computational solutions arising from numerical simulation results of a mathematical model of malignant solid tumour growth and invasion in an irregular heterogeneous three-dimensional domain, i.e., the female breast. Due to the different variables that interact with each other, more than one data set may have to be displayed simultaneously, which can be realized through transparency blending. The usefulness of the proposed method for visualisation in a more general context will also be discussed. PMID- 20361834 TI - Noise-sensitive measure for stochastic resonance in biological oscillators. AB - There has been ample experimental evidence that a variety of biological systems use the mechanism of stochastic resonance for tasks such as prey capture and sensory information processing. Traditional quantities for the characterization of stochastic resonance, such as the signal-to-noise ratio, possess a low noise sensitivity in the sense that they vary slowly about the optimal noise level. To tune to this level for improved system performance in a noisy environment, a high sensitivity to noise is required. Here we show that, when the resonance is understood as a manifestation of phase synchronization, the average synchronization time between the input and the output signal has an extremely high sensitivity in that it exhibits a cusp-like behavior about the optimal noise level. We use a class of biological oscillators to demonstrate this phenomenon, and provide a theoretical analysis to establish its generality. Whether a biological system actually takes advantage of phase synchronization and the cusp like behavior to tune to optimal noise level presents an interesting issue of further theoretical and experimental research. PMID- 20361835 TI - Lyapunov functions for tuberculosis models with fast and slow progression. AB - The spread of tuberculosis is studied through two models which include fast and slow progression to the infected class. For each model, Lyapunov functions are used to show that when the basic reproduction number is less than or equal to one, the disease-free equilibrium is globally asymptotically stable, and when it is greater than one there is an endemic equilibrium which is globally asymptotically stable. PMID- 20361836 TI - Mathematical modeling of biowall reactors for in-situ groundwater treatment. AB - In this paper we develop a comprehensive model for the remediation of contaminated groundwater in a passive, in-ground reactor, generally known as a biowall. The model is based on our understanding of the component transport and biokinetic processes that occur as water passes through a bed of inert particles on which a biofilm containing active microbial degraders, typically aerobic bacteria, is developing. We give a detailed derivation of the model based on accepted engineering formulations that account for the mass transport of the contaminant (substrate) to the surface of the biofilm, its diffusion into the biofilm to the proximity of a microbe, and its subsequent destruction within that degrader. The model has been solved numerically and incorporated in a robust computer code. Based on representative input values, the results of varying key parameters in the model are presented. The relation between biofilm growth and biowall performance is explored, revealing that the amount of biomass and its distribution within the biowall are key parameters affecting contaminant removal. PMID- 20361837 TI - Modeling shrimp biomass and viral infection for production of biological countermeasures. AB - In this paper we develop a mathematical model for the rapid production of large quantities of therapeutic and preventive countermeasures. We couple equations for biomass production with those for vaccine production in shrimp that have been infected with a recombinant viral vector expressing a foreign antigen. The model system entails both size and class-age structure. PMID- 20361838 TI - Modelling the human immune response mechanisms to mycobacterium tuberculosis infection in the lungs. AB - This work elaborates on the effects of cytotoxic lymphocytes (CTLs) and other immune mechanisms in determining whether a TB-infected individual will develop active or latent TB. It answers one intriguing question: why do individuals infected with Mycobacterium tuberculosis (Mtb) experience different clinical outcomes? In addressing this question, we have developed a model that captures the effects of CTLs and the combined effects of CD4+ helper T cells (Th1 and Th2) immune response mechanisms to TB infection. The occurrence of active or latent infection is shown to depend on a number of factors that include effector function and levels of CTLs. We use the model to predict disease progression scenarios, including primary, latency or clearance. Model analysis shows that occurrence of active disease is much attributed to the Mtb pathogen ability to persist outside the intracellular environment and that high levels of CTLs result in latent TB, while low levels of CTLs result in active TB. This is attributed to the CTLs' ability to directly kill infected macrophages and the bacteria inside the infected macrophages. The study suggests directions for further basic studies and potential new treatment strategies. PMID- 20361839 TI - Monte carlo simulation of heterotypic cell aggregation in nonlinear shear flow. AB - In this paper, we develop a population balance model for cell aggregation and adhesion process in a nonuniform shear flow. Some Monte Carlo simulation results based on the model are presented for the heterotypic cell-cell collision and adhesion to a substrate under dynamic shear forces. In particular, we focus on leukocyte (PMN)-melanoma cell emboli formation and subsequent tethering to the vascular endothelium (EC) as a result of cell-cell aggregation. The simulation results are compared with the results of experimental measurement. Discussions are made on how we could further improve the accuracy of the population balance type modelling. PMID- 20361840 TI - Complex spatio-temporal features in meg data. AB - Magnetoencephalography (MEG) brain signals are studied using a method for characterizing complex nonlinear dynamics. This approach uses the value of d(infinity) (d-infinite) to characterize the system's asymptotic chaotic behavior. A novel procedure has been developed to extract this parameter from time series when the system's structure and laws are unknown. The implementation of the algorithm was proven to be general and computationally efficient. The information characterized by this parameter is furthermore independent and complementary to the signal power since it considers signals normalized with respect to their amplitude. The algorithm implemented here is applied to whole head 148 channel MEG data during two highly structured yogic breathing meditation techniques. Results are presented for the spatio-temporal distributions of the calculated d(infinity) on the MEG channels, and they are compared for the dirrerent phases of the yogic protocol. The algorithm was applied to six MEG data sets recorded over a three-month period. This provides the opportunity of verifying the consistency of unique spatio-temporal features found in specific protocol phases and the chance to investigate the potential long term effects of these yogic techniques. Differences among the spatio-temporal patterns related to each phase were found, and they were independent of the power spatio-temporal distributions that are based on conventional analysis. This approach also provides an opportunity to compare both methods and possibly gain complementary information. PMID- 20361841 TI - On the stabilizing effect of cannibalism in stage-structured population models. AB - In this paper we give a contribution to the systematic investigation of cannibalism in predator-prey models commenced since the publication of the paper by Kohlmeier and Ebenhoh in 1995. We present a stage-structured predator-prey model and study its dynamics. We use a Hopf bifurcation analysis to prove that cycles are possible and that cannibalism suppresses these cycles; that is, when cannibalism attack rate is increased so that it passes a critical value, the coexistence steady state changes from being unstable to being stable. Numerical simulations are provided together with the mathematical analysis. Our modelling approach is based on balance arguments and a comparison with some early models which predict that a destabilizing effect of cannibalism is performed. Our results agree with the output of growth simulation for some cannibalistic copepods. PMID- 20361842 TI - Capsule endoscopy and nonsteroidal anti-inflammatory drugs (NSAID)-induced enteropathy--a bit of light in a long, dark tunel. PMID- 20361843 TI - Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti inflammatory drugs (NSAID) use as assessed by capsule endoscopy. AB - OBJECTIVE: To evaluate the type, frequency, and severity of macroscopic small bowel mucosal injury after chronic NSAID intake as assessed by capsule endoscopy (CE), as well as to correlate the severity of gastroduodenal and intestinal damage in these patients. MATERIAL AND METHODS: A prospective, endoscopist-blind, controlled trial. Sixteen patients (14F/2M; age: 57.06 +/- 10.16 yrs) with osteoarthritis (OA) on chronic therapy with NSAIDs underwent CE and upper gastrointestinal endoscopy (UGE). Seventeen patients with OA (9F/2M; age: 57.47 +/- 9.82 yrs) who did not take NSAIDs were included as a control group. A scale ranging from 0 to 2 (0 = no lesions, 1-minor = red spots or petechiae, denuded areas and/or 1-5 mucosal breaks; 2-major = > 5 mucosal breaks and/or strictures, or hemorrhage) was designed to assess the severity of small bowel mucosal injuries. RESULTS: CE found intestinal lesions in 75% (12/16) of patients in the study group and in 11.76% (2/17) of controls (p < 0.01). Seven out of 16 NSAID consumers (43.75%) and none in the control group (0%) had a major small bowel mucosal injury (p < 0.01). The percentages of patients with grade 1 and 2 gastroduodenopathy in the study group, as assessed by UGE, were 37.14 and 23.81%, respectively. There was no significant difference in the rate of major enteropathy between patients with none or minor gastroduodenal injury, and those with major gastroduodenopathy (43.75 vs. 40%; p = N.S.). CONCLUSIONS: Chronic NSAID intake is associated with a high rate of small bowel mucosal injuries. Our data have failed to demonstrate a relationship between the severity of gastroduodenal and intestinal injury. PMID- 20361844 TI - Capnography is superior to pulse oximetry for the detection of respiratory depression during colonoscopy. AB - BACKGROUND: Pulse oximetry is a widely accepted procedure for ventilatory monitoring during gastrointestinal endoscopy, but this method provides an indirect measurement of the respiratory function. In addition, detection of abnormal ventilatory activity can be delayed, especially if supplemental oxygen is provided. Capnography offers continuous real-time measurement of expiratory carbon dioxide. OBJECTIVE: We aimed at prospectively examining the advantages of capnography over the standard pulse oximetry monitoring during sedated colonoscopies. PATIENTS AND METHODS: Fifty patients undergoing colonoscopy were simultaneously monitored with pulse oximetry and capnography by using two different devices in each patient. Several sedation regimens were administered. Episodes of apnea or hypoventilation detected by capnography were compared with the occurrence of hypoxemia. RESULTS: Twenty-nine episodes of disordered respiration occurred in 16 patients (mean duration 54.4 seconds). Only 38% of apnea or hypoventilation episodes were detected by pulse oximetry. A mean delay of 38.6 seconds was observed in the events detected by pulse oximetry (two episodes of disturbed ventilation were simultaneously detected by capnography and pulse oximetry). CONCLUSIONS: Apnea or hypoventilation commonly occurs during colonoscopy with sedation. Capnography is more reliable than pulse oximetry in early detection of respiratory depression in this setting. PMID- 20361845 TI - Pyogenic versus amoebic liver abscesses. A comparative clinical study in a series of 58 patients. AB - OBJECTIVE: To compare the clinical and epidemiological characteristics of patients with pyogenic liver abscess (PLA) and with amebic liver abscess (AHA) in order to determine the potential factors that may help improve diagnosis and treatment for this disease. MATERIAL AND METHOD: A retrospective study of clinical histories of 45 patients with PLA and 13 with ALA, diagnosed between 1985 and 2005 in Donostia Hospital in San Sebastian. RESULTS: Among the 45 patients with PLA (30 men and 15 women, with a mean age of 61 years and 11 months), more than a half were cholangitic (13 cases) or were of unknown origin (15 cases). In 10 patients, diabetes was considered to be a predisposing condition. Increased ESR (> 30), leukocytosis (> 12,000), fever and abdominal pain were observed in 95.5%, 86.7%, 82.8% and 68.9%, respectively. Twenty-five patients had single abscesses. Abscess and blood cultures were positive in 77.1% and 50% of cases, respectively (44.4% with polymicrobial infection). E. coli and S. milleri were the most commonly found germs. A percutaneous drainage was performed on 22 patients. Mean hospital stay was 27 days, and overall mortality, including that related to concomitant conditions, was 7 of 45 cases.Of the 13 cases of ALA (7 men and 6 women, with mean age of 42,9 years), 2 were locally acquired. Increased AF and GGTP (> 2N), fever, leukocytosis and ESR (> 30) were observed in 92.3, 77, 70 and 61.5% of cases, respectively. There were single abscesses in 10 patients and all except one were located in the right lobe. The serological test for E. histolytica (IFF > or = 1/256) was positive in 100% of cases. A percutaneous drainage was carried out on 6 patients. Mean hospital stay was 18 days and two patients died. CONCLUSIONS: In our series, the clinical parameters suggesting pyogenic origin were: age 50 or older, male gender, diabetes, moderately elevated bilirubin and transaminases. In amoebic cases the associated features were being aged 45 or younger, diarrhoea, and presence of a single abscess in the right lobe. Parasitism by E. histolytica must be considered in the differential diagnosis of liver abscesses, even with no epidemiological clinical history of travel and/or immigration. PMID- 20361846 TI - A retrospective study of pediatric endoscopy as performed in an adult endoscopy unit. AB - Gastrointestinal endoscopy is a safe, efficient technique with minimal complications, and a useful diagnostic tool for the pediatric population. Under ideal conditions endoscopies for children should be performed by experienced pediatric endoscopists. In this study we report our experience with pediatric endoscopy at the general adult endoscopy unit in our hospital. Our goal is to quantify the number of endoscopies performed in children, as well as their indications and findings, the type of sedation or anesthesia used, and the time waiting for the test to occur. Our experience demonstrates that endoscopists in a general adult gastroenterology department, working together with pediatricians, may perform a relevant number of endoscopies in children in a fast, safe, effective manner. PMID- 20361847 TI - Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001. AB - BACKGROUND: To determine the epidemiological, clinical, diagnostic and therapeutic characteristics of Whipple s disease in Spain. PATIENTS AND METHOD: Cases of Whipple s disease reported in the Spanish literature between 1947 and 2001 which meet histological or PCR criteria are reviewed. RESULTS: 91 cases were included, 87.5% of which were male. The maximum incidence was between 40 and 60 years of age (68%). There was no family clustering or susceptibility by profession or surroundings. The most common symptoms and signs were: weight loss (80%), diarrhoea (63%), adenopathies (35%), skin problems (32%), abdominal pain (27%), fever (23%), joint problems (20%) and neurological problems (16%). Arthralgias, diarrhoea and fever were noted prior to diagnosis in 58, 18 and 13% of patients, respectively. Diagnosis was histological in all cases except two, which were diagnosed by PCR. Intestinal biopsy was positive in 94%. Adenopathic biopsies (mesenteric or peripheral) were suggestive in 13% of cases, and treatment was effective in 89%. There were nine relapses, four of which were neurological, although all occurred before the introduction of cotrimoxazole. CONCLUSIONS: Whipple s disease is not uncommon, although it requires a high degree of suspicion to be diagnosed in the absence of digestive symptoms. The most common and most sensitive diagnostic method is duodenal biopsy. PCR is beginning to be introduced to confirm the diagnosis and as a therapeutic control. Initial antibiotic treatment with drugs that cross the blood-brain barrier, such as cotrimoxazole and ceftriaxone, is key to achieving a cure and avoiding relapses. PMID- 20361848 TI - Clinical practice guidelines for managing coagulation in patients undergoing endoscopic procedures. PMID- 20361849 TI - Unusual subcutaneous manifestation of severe acute pancreatitis. PMID- 20361850 TI - Ectopic sebaceous glands in the esophagus. PMID- 20361851 TI - Acute jejunal diverticulitis due to a foreign body. PMID- 20361852 TI - Infliximab therapy in a patient with refractory ileocolic Crohn's disease and Takayasu arteritis. PMID- 20361853 TI - Malignant fibrous histiocytoma--a rare hepatic tumor. PMID- 20361854 TI - Hypercalcemia worsened by the use of furosemide in a patient suffering from allopurinol-induced granulomatous hepatitis. PMID- 20361855 TI - Role of redox signaling, protein phosphatases and histone acetylation in the inflammatory cascade in acute pancreatitis. Therapeutic implications. AB - Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation triggered by histone acetyltransferases, particularly CBP/p300, decisively contribute to the activation phase of the inflammatory cascade. Reversible oxidation of thiols in serine threonine protein phosphatase PP2A and in protein tyrosin phosphatases SHP1, SHP2 and CD45 leads to their inactivation generally by formation of intramolecular disulfides. Consequently, oxidative stress promotes the activation of MAP kinases through the inactivation of protein phosphatases, which act as sensors of the cellular redox state. On the other hand, histone deacetylases together with serine threonine protein phosphatases PP1 and PP2A and dual specificity phosphatases down-regulate the expression of pro-inflammatory genes in the attenuation phase. Treatment with phosphodiesterase inhibitors, such as pentoxifylline, in the very early stage of the disease prevents the loss of pancreatic PP2A activity abrogating the recruitment of histone acetyltransfereases to the promoters of pro-inflammatory genes and their up regulation. Inhibitors of histone deacetylases are also proposed as potential therapy in acute pancreatitis, and their therapeutic window discussed. PMID- 20361856 TI - Sparse partial least squares classification for high dimensional data. AB - Partial least squares (PLS) is a well known dimension reduction method which has been recently adapted for high dimensional classification problems in genome biology. We develop sparse versions of the recently proposed two PLS-based classification methods using sparse partial least squares (SPLS). These sparse versions aim to achieve variable selection and dimension reduction simultaneously. We consider both binary and multicategory classification. We provide analytical and simulation-based insights about the variable selection properties of these approaches and benchmark them on well known publicly available datasets that involve tumor classification with high dimensional gene expression data. We show that incorporation of SPLS into a generalized linear model (GLM) framework provides higher sensitivity in variable selection for multicategory classification with unbalanced sample sizes between classes. As the sample size increases, the two-stage approach provides comparable sensitivity with better specificity in variable selection. In binary classification and multicategory classification with balanced sample sizes, the two-stage approach provides comparable variable selection and prediction accuracy as the GLM version and is computationally more efficient. PMID- 20361857 TI - Reconstructability analysis as a tool for identifying gene-gene interactions in studies of human diseases. AB - There are a number of common human diseases for which the genetic component may include an epistatic interaction of multiple genes. Detecting these interactions with standard statistical tools is difficult because there may be an interaction effect, but minimal or no main effect. Reconstructability analysis (RA) uses Shannon's information theory to detect relationships between variables in categorical datasets. We applied RA to simulated data for five different models of gene-gene interaction, and find that even with heritability levels as low as 0.008, and with the inclusion of 50 non-associated genes in the dataset, we can identify the interacting gene pairs with an accuracy of > or =80%. We applied RA to a real dataset of type 2 non-insulin-dependent diabetes (NIDDM) cases and controls, and closely approximated the results of more conventional single SNP disease association studies. In addition, we replicated prior evidence for epistatic interactions between SNPs on chromosomes 2 and 15. PMID- 20361858 TI - Integrated nursing access program: an approach to prepare aboriginal students for nursing careers. AB - The challenge to transfer the health care of Aboriginal peoples of Canada from non-Aboriginal to predominantly Aboriginal health professionals, requires preliminary innovative approaches in post-secondary education. Described in this paper, is the background, development and progress to date of the Integrated Nursing Access Program (INAP) for Aboriginal students, and its phenomenological approach to curriculum design. Traditional indigenous knowledge and methodologies are embedded in process learning and university-level program activities. Learning in this INAP Bachelor of Nursing program occurs over three years, during which time students complete high school requirements together with some first year nursing courses. The program is followed by three additional years of exclusive baccalaureate level nursing education. To date, students have successfully completed the first half of this program. PMID- 20361859 TI - Theory-based research of high fidelity simulation use in nursing education: a review of the literature. AB - In this article, we explore the extent to which theory-based research is informing our understanding of high-fidelity simulation use in nursing education. We reviewed the primary literature archived in the Cumulative Index of Nursing and Applied Health Literature (CINAHL) and Proquest Dissertation and Theses for empirical reports using the key terms high-fidelity simulation and nursing from the years 1989 to 2009. Of the articles that matched our inclusion criteria: 45% made no use of theory; 45% made minimal use; and 10% made adequate use. We argue that theory-based research could bring coherence and external validity to this domain. PMID- 20361860 TI - Online learning versus simulation for teaching principles of mechanical ventilation to nurse practitioner students. AB - Patient simulation is increasingly used in the education of healthcare providers, yet few studies have compared simulation to other teaching modalities. The purpose of this study was to determine differences in knowledge acquisition and student satisfaction between two methods of teaching the principles of mechanical ventilation to advanced practice nursing (APN) students: high-fidelity patient simulation (including face-to-face instruction) versus an online, narrated PowerPoint presentation. Twenty APN students were randomized to either the simulation or online teaching method in this pre/posttest study. Measures included a 12-item knowledge questionnaire and a 5-item satisfaction survey. Both groups had significant improvement in knowledge scores from pretest to posttest, but knowledge scores were not significantly different at posttest between groups. Student satisfaction with their learning method was significantly higher in the simulation group. Students choosing to participate in the alternative teaching method after study completion preferred the simulation to the online method. PMID- 20361861 TI - The development of nurse practitioner preparation beyond the master's level: what is the debate about? AB - The nursing discipline in the United States (US) has a history of creating various doctorates. One such degree, the Doctor of Nursing Practice (DNP), serves as an alternative to the traditional Doctor of Philosophy (PhD) degree for Nurse Practitioners (NPs) exploring career options. The availability of the DNP has sparked a debate within the profession: close attention to the issues is warranted for any school considering the development of a DNP program. However, some of these issues are not applicable, or apply differently to other contexts including Canada, where the highest level of education for an NP is a PhD. This article will review the history of doctoral education in both countries, compare the practice-focused and research-focused doctorates, discuss the issues of debate, and explore implications for NP practice. To fully inform the decision of the NP, we recommend further research to explore the need for a practice doctorate. PMID- 20361862 TI - Five simple rules for treating pediatric intermitttent exotropia strabismus. PMID- 20361863 TI - Future of medicine and the profession; universal serotonin addiction? exotropia five rules; safer strabismus surgery; pinealoma; MS Corectopia. PMID- 20361864 TI - A new modfied anchored suspension-recession (so-called "hang-back" technique for high risk strabismus surgery. AB - PURPOSE: To intruduce a new method for rectus muscle recession in order to minimize the riSk of a lost or slipped muscle and scleral perforation and compare it with the conventional method. PATIENTS AND METHODS: In a prospective study between May 2002 and December 2006, 69 patients underwent recession with the modified technique, and 50 patients underwent recession with the conventional method. We compared the results of strabismus surgery in these non-randomized series with esotropia or exotropia treated with conventional surgery with the modified technique surgery. Patients in the modified technique group were high risk patients that had large angle recession, thin sclera or less exposure sugical field. RESULTS: Surgical outcomes were not significantly different in the two treatment groups that based on their findings had been classified into four subgroups. No complications such as globe penetration, muscle slippage or lost muscle were observed during the follow up period of 12 months. CONCLUSIONS: It seems that the modified method introduced in this study can reduce the complications and risks involved in conventional and suspension-recession methods and it is safe and effective for muscle recession. It can decrease the risk of globe perforation since the sclera behind the insertion is penetrated only superficially because of anchor suturing to the muscle insertion stump, and the possibility of lost or slipped recessed muscles would be minimized. PMID- 20361865 TI - Isolated inferior rectus paresis with falling eye phenomenon of the contralateral eye in a patient with pineal tumor: a case report. AB - PRUPOSE: To report a patient who developed an isolated inferior rectus paresis due to a pineal gland tumor, and to our knowledge never reported before. Our purpose is also to demonstrate that, even in partial and mild inferior rectus muscle paresis, the findings of the inhibitional palsy described by Chavasse and the downshoot of the fellow eye in adduction help determine the diagnosis. CASE REPORT: A patient with pineal gland tumor demonstrated findings characteristic of unilateral isolated inferior rectus paresis. CONCLUSION: Although bilateral sixth nerve paresis and Parinaud's syndrome are commonly reported in pineal gland tumors; in the the presence of an isolated inferior rectus palsy, one should also consider the pineal gland as the causative factor. PMID- 20361866 TI - Incidental detection of bilateral corectopia by photo screening leads to the diagnosis of multiple sclerosis. A case report. AB - PURPOSE: To describe a case of an incidental finding of bilateral corectopia detected by photo screening which ultimately led to the diagnosis of multiple sclerosis. METHODS: Case presentation and literature review. RESULTS: Corectopia may be congenital or acquired. Midbrain corectopia is commonly caused by infarction and demyelinating disease can cause autonomic pupil abnormalities resulting in corectopia. CONCLUSION: A careful history and ocular examinatin can aid in determining the etiology of corectopia. Additional genetics or neurologic consultation may be necessary to diagnosis systemic disease. PMID- 20361867 TI - Globin-like proteins in Caenorhabditis elegans: in vivo localization, ligand binding and structural properties. AB - BACKGROUND: The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression. RESULTS: We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 --> Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over three alpha-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding. CONCLUSION: The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes. PMID- 20361868 TI - Predicting protein-protein interactions in unbalanced data using the primary structure of proteins. AB - BACKGROUND: Elucidating protein-protein interactions (PPIs) is essential to constructing protein interaction networks and facilitating our understanding of the general principles of biological systems. Previous studies have revealed that interacting protein pairs can be predicted by their primary structure. Most of these approaches have achieved satisfactory performance on datasets comprising equal number of interacting and non-interacting protein pairs. However, this ratio is highly unbalanced in nature, and these techniques have not been comprehensively evaluated with respect to the effect of the large number of non interacting pairs in realistic datasets. Moreover, since highly unbalanced distributions usually lead to large datasets, more efficient predictors are desired when handling such challenging tasks. RESULTS: This study presents a method for PPI prediction based only on sequence information, which contributes in three aspects. First, we propose a probability-based mechanism for transforming protein sequences into feature vectors. Second, the proposed predictor is designed with an efficient classification algorithm, where the efficiency is essential for handling highly unbalanced datasets. Third, the proposed PPI predictor is assessed with several unbalanced datasets with different positive-to-negative ratios (from 1:1 to 1:15). This analysis provides solid evidence that the degree of dataset imbalance is important to PPI predictors. CONCLUSIONS: Dealing with data imbalance is a key issue in PPI prediction since there are far fewer interacting protein pairs than non interacting ones. This article provides a comprehensive study on this issue and develops a practical tool that achieves both good prediction performance and efficiency using only protein sequence information. PMID- 20361869 TI - PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells. AB - BACKGROUND: PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive. RESULTS: We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing. Invasion assay suggested that PCBP1 played a negative role in tumor invasion and re-expression of v6 partly reversed the inhibition effect by PCBP1. A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues. CONCLUSIONS: We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype. PMID- 20361870 TI - A method for managing re-identification risk from small geographic areas in Canada. AB - BACKGROUND: A common disclosure control practice for health datasets is to identify small geographic areas and either suppress records from these small areas or aggregate them into larger ones. A recent study provided a method for deciding when an area is too small based on the uniqueness criterion. The uniqueness criterion stipulates that an the area is no longer too small when the proportion of unique individuals on the relevant variables (the quasi identifiers) approaches zero. However, using a uniqueness value of zero is quite a stringent threshold, and is only suitable when the risks from data disclosure are quite high. Other uniqueness thresholds that have been proposed for health data are 5% and 20%. METHODS: We estimated uniqueness for urban Forward Sortation Areas (FSAs) by using the 2001 long form Canadian census data representing 20% of the population. We then constructed two logistic regression models to predict when the uniqueness is greater than the 5% and 20% thresholds, and validated their predictive accuracy using 10-fold cross-validation. Predictor variables included the population size of the FSA and the maximum number of possible values on the quasi-identifiers (the number of equivalence classes). RESULTS: All model parameters were significant and the models had very high prediction accuracy, with specificity above 0.9, and sensitivity at 0.87 and 0.74 for the 5% and 20% threshold models respectively. The application of the models was illustrated with an analysis of the Ontario newborn registry and an emergency department dataset. At the higher thresholds considerably fewer records compared to the 0% threshold would be considered to be in small areas and therefore undergo disclosure control actions. We have also included concrete guidance for data custodians in deciding which one of the three uniqueness thresholds to use (0%, 5%, 20%), depending on the mitigating controls that the data recipients have in place, the potential invasion of privacy if the data is disclosed, and the motives and capacity of the data recipient to re-identify the data. CONCLUSION: The models we developed can be used to manage the re-identification risk from small geographic areas. Being able to choose among three possible thresholds, a data custodian can adjust the definition of "small geographic area" to the nature of the data and recipient. PMID- 20361871 TI - The Jamaica asthma and allergies national prevalence survey: rationale and methods. AB - BACKGROUND: Asthma is a significant public health problem in the Caribbean. Prevalence surveys using standardized measures of asthma provide valid prevalence estimates to facilitate regional and international comparisons and monitoring of trends. This paper describes methods used in the Jamaica Asthma and Allergies National Prevalence Survey, challenges associated with this survey and strategies used to overcome these challenges. METHODS/DESIGN: An island wide, cross sectional, community-based survey of asthma, asthma symptoms and allergies was done among adults and children using the European Community Respiratory Health Survey Questionnaire for adults and the International Study of Asthma and Allergies in Children. Stratified multi-stage cluster sampling was used to select 2, 163 adults aged 18 years and older and 2, 017 children aged 2-17 years for the survey. The Kish selection table was used to select one adult and one child per household. Data analysis accounted for sampling design and prevalence estimates were weighted to produce national estimates. DISCUSSION: The Jamaica Asthma and Allergies National Prevalence Survey is the first population- based survey in the Caribbean to determine the prevalence of asthma and allergies both in adults and children using standardized methods. With response rates exceeding 80% in both groups, this approach facilitated cost-effective gathering of high quality asthma prevalence data that will facilitate international and regional comparison and monitoring of asthma prevalence trends. Another unique feature of this study was the partnership with the Ministry of Health in Jamaica, which ensured the collection of data relevant for decision-making to facilitate the uptake of research evidence. The findings of this study will provide important data on the burden of asthma and allergies in Jamaica and contribute to evidence-informed planning of comprehensive asthma management and education programs. PMID- 20361872 TI - Parvovirus B19 infection and severe anaemia in Kenyan children: a retrospective case control study. AB - BACKGROUND: During acute Human parvovirus B19 (B19) infection a transient reduction in blood haemoglobin concentration is induced, due to a 5-7 day cessation of red cell production. This can precipitate severe anaemia in subjects with a range of pre-existing conditions. Of the disease markers that occur during B19 infection, high IgM levels occur closest in time to the maximum reduction in haemoglobin concentration. Previous studies of the contribution of B19 to severe anaemia among young children in Africa have yielded varied results. This retrospective case/control study seeks to ascertain the proportion of severe anaemia cases precipitated by B19 among young children admitted to a Kenyan district hospital. METHODS: Archival blood samples from 264 children under 6 years with severe anaemia admitted to a Kenyan District Hospital, between 1999 and 2004, and 264 matched controls, were tested for B19 IgM by Enzyme Immunosorbent Assay and 198 of these pairs were tested for B19 DNA by PCR. 536 samples were also tested for the presence of B19 IgG. RESULTS: 7 (2.7%) cases and 0 (0%) controls had high B19 IgM levels (Optical Density > 5 x cut-off value) (McNemar's exact test p = 0.01563), indicating a significant association with severe anaemia. The majority of strongly IgM positive cases occurred in 2003.10/264 (3.7%) cases compared to 5/264 (1.9%) controls tested positive for B19 IgM. This difference was not statistically significant, odds ratio (OR) = 2.00 (CI95 [0.62, 6.06], McNemar's exact test p = 0.3018. There was no significant difference between cases and controls in the B19 IgG (35 (14.8%) vs 32 (13.6%)), OR = 1.103 (CI95 [0.66, 1.89], McNemar's exact test, p = 0.7982), or the detection of the B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2 (CI95 [0.33, 4.01], McNemar's exact test p = 1). CONCLUSIONS: High B19 IgM levels were significantly associated with severe anaemia, being found only among the cases. This suggests that 7/264 (2.7%) of cases of severe anaemia in the population of children admitted to KDH were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data that shows that less than 15% of children in the study were exposed to B19, a figure much lower than reported in other tropical areas. PMID- 20361873 TI - Multiple sclerosis and pregnancy: what does the patient think? a questionnaire study. AB - BACKGROUND: Multiple Sclerosis (MS) is primarily a disease of women in their childbearing years. Pregnancy and puerperium have opposite effects on the course of the disease. Nevertheless, no studies have been carried out yet on the level of information among female MS-patients regarding the interaction between MS and pregnancy. FINDINGS: Demographic data, clinical features of MS, course of MS during pregnancy and puerperium as well as knowledge concerning MS and pregnancy were evaluated by means of a questionnaire in 154 female MS-patients. The level of information was significantly higher (p < 0.001) in women who had been pregnant in the past with the diagnosis MS known at this point of time. Furthermore patients reported about a lower frequency of relapses during pregnancy and a higher frequency of relapses in the first six months after giving birth. CONCLUSIONS: The findings illustrate a lack of knowledge in female MS patients concerning the interactions of MS and pregnancy. In order to make their own independent decision based on scientific facts known to date, female MS patients need to be better informed on issues regarding MS and pregnancy. PMID- 20361875 TI - Socioeconomic factors differentiating maternal and child health-seeking behavior in rural Bangladesh: A cross-sectional analysis. AB - BACKGROUND: There has been an increasing availability and accessibility of modern health services in rural Bangladesh over the past decades. However, previous studies on the socioeconomic differentials in the utilization of these services were based on a limited number of factors, focusing either on preventive or on curative modern health services. These studies failed to collect data from remote rural areas of the different regions to examine the socioeconomic differentials in health-seeking behavior. METHODS: Data from 3,498 randomly selected currently married women from three strata of households within 128 purposively chosen remote villages in three divisions of Bangladesh were collected in 2006. This study used bivariate and multivariate logistic analyses to examine both curative and preventive health-seeking behaviors in seven areas of maternal and child health care: antenatal care, postnatal care, child delivery care, mother's receipt of Vitamin A postpartum, newborn baby care, care during recent child fever/cough episodes, and maternal coverageby tetanus toxoid (TT). RESULTS: A principal finding was that a household's relative poverty status, as reflected by wealth quintiles, was a major determinant in health-seeking behavior. Mothers in the highest wealth quintile were significantly more likely to use modern trained providers for antenatal care, birth attendance, post natal care and child health care than those in the poorest quintile (chi2, p < 0.01). The differentials were less pronounced for other factors examined, such as education, age, and the relative decision-making power of a woman, in both bivariate and multivariate analyses. CONCLUSION: Within rural areas of Bangladesh, where overall poverty is greater and access to health care more difficult, wealth differentials in utilization remain pronounced. Those programs with high international visibility and dedicated funding (e.g., Immunization and Vitamin A delivery) have higher overall prevalence and a more equitable distribution of beneficiaries than the use of modern trained providers for basic essential health care services. Implications of these findings and recommendations are provided. PMID- 20361874 TI - Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes. AB - BACKGROUND: New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Saccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset. RESULTS: Cross species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from Ancylostoma caninum and Haemonchus contortus--two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools. CONCLUSIONS: The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host. PMID- 20361876 TI - Developmental dynamics of Ambystoma tigrinum in a changing landscape. AB - BACKGROUND: Loss of pond habitat is catastrophic to aquatic larval amphibians, but even reduction in the amount of time a breeding site holds water (hydroperiod) can influence amphibian development and limit reproductive success. Using the landscape variation of a glacial valley in the Greater Yellowstone Ecosystem as the context for a natural experiment, we examined variation in growth pattern and life history of the salamander Ambystoma tigrinum melanostictum and determined how these developmental characteristics varied with hydroperiod over several summers. RESULTS: In ponds that dried early in the season, maximum larval size was reduced relative to the sizes achieved in permanent ponds. Ephemeral ponds were associated with early metamorphosis at small body sizes, while permanent ponds facilitated longer larval periods and later metamorphosis. Paedomorphosis resulted from indefinite metamorphic postponement, and was identified only in the most permanent environments. Patterns of growth and allometry were similar between ponds with different hydroperiods, but considerable life history variation was derived from modulating the timing of and size at metamorphosis. Considering maximum rates of growth and inferring the minimum size at metamorphosis across 25 ponds over the course of three years, we calculated that hydroperiods longer than three months are necessary to support these populations through metamorphosis and/or reproductive maturity. CONCLUSIONS: Landscape heterogeneity fosters life history variation in this natural population. Modulation of the complex ambystomatid life cycle allows this species to survive in unpredictable environments, but current trends towards rapid pond drying will promote metamorphosis at smaller sizes and could eliminate the paedomorphic phenotype from this region. Metamorphosis at small size is has been linked to altered fitness traits, including reduced survival and fecundity. Thus, widespread environmental truncation of larval periods may lead to decreased population persistence. We found that the hydroperiods of many ponds in this region are now shorter than the developmental period required for larvae to reach the minimum size for metamorphosis; these locations serve as reproductive sinks that may be detrimental for persistence of the species in the region. PMID- 20361877 TI - Surveillance of FAP: a prospective blinded comparison of capsule endoscopy and other GI imaging to detect small bowel polyps. AB - BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary disorder characterized by polyposis along the gastrointestinal tract. Information on adenoma status below the duodenum has previously been restricted due to its inaccessibility in vivo. Capsule Endoscopy (CE) may provide a useful adjunct in screening for polyposis in the small bowel in FAP patients. This study aims to evaluate the effectiveness of CE in the assessment of patients with FAP, compared to other imaging modalities for the detection of small bowel polyps. METHOD: 20 consecutive patients with previously diagnosed FAP and duodenal polyps, presenting for routine surveillance of polyps at The Royal Melbourne Hospital were recruited. Each fasted patient initially underwent a magnetic resonance image (MRI) of the abdomen, and a barium small bowel follow-through study. Capsule Endoscopy was performed four weeks later on the fasted patient. An upper gastrointestinal side-viewing endoscopy was done one (1) to two (2) weeks after this. Endoscopists and investigators were blinded to results of other investigations and patient history. RESULTS: Within the stomach, upper gastrointestinal endoscopy found more polyps than other forms of imaging. SBFT and MRI generally performed poorly, identifying fewer polyps than both upper gastrointestinal and capsule endoscopy. CE was the only form of imaging that identified polyps in all segments of the small bowel as well as the only form of imaging able to provide multiple findings outside the stomach/duodenum. CONCLUSION: CE provides important information on possible polyp development distal to the duodenum, which may lead to surgical intervention. The place of CE as an adjunct in surveillance of FAP for a specific subset needs consideration and confirmation in replication studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12608000616370. PMID- 20361881 TI - Effect of aloe cream versus silver sulfadiazine for healing burn wounds in rats. AB - The management of burn injury remains a problem and it is the major cause of death and disability. The aim of this study was to evaluate the efficacy of Aloe vera cream in the treatment of thermal burn wounds and to compare these results with silver sulfadiazine in rats. Animals were divided into four groups. Animals were administered topical cream (Aloe vera powdered gel 0.5% and silver sulfadiazine) at 24 h of burn injury induced by hot water. On special days, according to study protocol, wound size was determined and skin sample histopathology performed in animal groups administered topical therapies. On day 25, the mean wound size was 5.5, 4, 0.78 and 4.1 cm2 in control, base, aloe and silver group, respectively. The wound size was significantly smaller in aloe group as compared with other groups. Histologic comparison showed aloe to increase reepithelialization in burn wounds significantly as compared with other cream-treated wounds. The results of this study showed aloe cream to significantly increase reepithelialization in burn wounds as compared with silver sulfadiazine. PMID- 20361882 TI - Scopulariopsis brevicaulis as the cause of dermatomycosis. AB - Scopulariopsis (S.) brevicaulis (Saccardo) Bainier 1907 is a ubiquitous fungus frequently isolated as a saprophyte from various layers of the soil, wood, straw, paper, food, and occasionally in animals and humans. This nondermatophyte filamentous fungus is multiresistant and is frequently associated with onychomycosis in humans. In the last two decades, the number of reports on its pathogenic role in different localized and disseminated infections has been on an increase. Identification was done by native KOH microscopy and culture on the Mycobios selective agar (Biolife). From January 1, 2002 till January 23, 2008, a total of 7161 samples were examined by use of mycology methods; S. brevicaulis accounted for 39 (2.2%) of 1834 (25.6%) positive samples. During the study period, S. brevicaulis was isolated from nail, skin and scalp scrapings of 39 patients (17 male and 22 female), mean age ( SD) 43.920.7 (range 8-87) years. Specimens were most frequently obtained from the foot (n=16; 41%), i.e. great toe nail in 10 and other foot areas in 6 cases, followed by palm and fingers in 8 (20.5%), scalp in 3 (7.7%) and other parts of the body in 12 (30.8%) cases. Most of the study subjects lived in a rural setting (n=22; 56%), working as farmers in close contact with the soil and domestic animals. Seventeen (44%) subjects were from urban setting (n=9) or unknown place of residence (n=8). Underlying risk factors were present in 29 (74%) of 39 study subjects, some of them with multiple risk factors. Besides close contact with the soil, the most common predisposing factors were various dermatoses (atopic dermatitis, psoriasis, dysseborrhea, etc.), lower extremity circulatory insufficiency, trauma, microtrauma, and metabolic disorders. Although the clinical picture of onychomycosis caused by S. brevicaulis shows some specific features, timely sampling for mycology is crucial to verify the diagnosis and to identify the causative agent prior to the introduction of appropriate therapy for dermatomycosis. PMID- 20361883 TI - Our experiences with the use of atopy patch test in the diagnosis of cow's milk hypersensitivity. AB - Atopy patch test has been recognized as a diagnostic tool for the verification of food allergies in infants and small children suffering from atopic dermatitis. The test also has a role in the diagnosis of food allergies characterized by clinical signs associated with the digestive system. Yet, in spite of numerous studies, the test itself has hitherto not been standardized. Our study enlisted 151 children less than two years of age, who exhibited suspect skin and/or gastrointestinal manifestations of food allergy to cow's milk, and in whom tests failed to prove early type of allergic reaction. Atopy patch test was positive in 28% of the children with atopic dermatitis, 43% of the children with suspect gastrointestinal manifestation and 32% of the children with skin and gastrointestinal manifestations of food allergy. In our experience, atopy patch test is an excellent addition to the hitherto used tests for the diagnosis of food allergies. It targets specifically delayed type hypersensitivity reactions, which are difficult to confirm with other diagnostic tools. It is furthermore simple to perform, noninvasive and produces a minimum of undesired side effects. For these reasons, it should become part of the routine diagnostic toolset for food allergies to cow's milk in infants and children, and applied before a food challenge test. PMID- 20361884 TI - Vitiligo and glaucoma - an association or a coincidence? A pilot study. AB - Our aim was to draw attention of clinicians, dermatovenereologists and ophthalmologists to the possible association of vitiligo and ocular findings characteristic of primary open angle glaucoma (POAG). According to our clinical experience, POAG is relatively often diagnosed or previously diagnosed in patients treated for vitiligo. We found no literature report directly connecting vitiligo and POAG. The articles mentioning glaucoma, i.e. increased intraocular pressure (IOP), are mainly based on secondary type of glaucoma as a direct consequence of vitiligo treated by corticosteroids. On the other hand, there is a substantial number of articles elaborating the association of vitiligo with ocular findings in known clinical syndromes. During a 2-year period, from May 2007 to May 2009, 42 patients with vitiligo were examined at University Department of Dermatology and Venereology and referred for previously appointed ophthalmologic examination at University Department of Ophthalmology, Split University Hospital Center. All patients with vitiligo underwent complete ophthalmologic examination including visual field analysis, in order to treat and follow up or diagnose newly discovered POAG. Of 42 patients with vitiligo suspect of glaucoma, POAG was confirmed in 24 (57%) patients. Age median of all vitiligo patients was 56 (range 19-82) years. In patients with vitiligo and glaucoma, the duration of vitiligo was twofold that recorded in patients with vitiligo alone, the difference being statistically significant (z=3.3; P<0.001). The risk of developing glaucoma in vitiligo patients was 4.4-fold in >56 age group versus <56 age group and 3.5-fold in patients with >13 year versus patients with <13 year duration of vitiligo. Multivariate logistic regression for glaucoma development according to vitiligo duration (< or =13 years vs. > or =13 years) and patient age (< or =56 years vs. > or =56 years) pointed to the association of glaucoma development and age and yielded a 92% probability for the association of glaucoma development and vitiligo duration. Therefore, we believe that patients treated for vitiligo should regularly undergo complete ophthalmologic examination with special attention paid to POAG irrespective of age, sex, severity, localization and duration of the disease. Although performed in a relatively small sample and over short period of time, the results of this pilot study demonstrated that this association was not accidental. Additional studies in a greater sample of vitiligo patients and POAG are expected to provide definitive answers and conclusion on the association of these two diseases. PMID- 20361885 TI - Abundance of plasma cells in a case of lipodermatosclerosis. AB - Plasma cells have been considered as an important morphological clue in the diagnosis of some sclerosing cutaneous diseases such as morphea, so much so that humoral immunology has been suggested to have a role in the pathogenesis of such diseases. Nevertheless, they are hardly ever described as a prominent feature in lipodermatosclerosis in which granulocytes have been claimed as the main pathogenic cell. We report a case of lipodermatosclerosis in a 77-year-old woman, in which plasma cells were abundant in the thickened fibrous septa of the hypodermis. They were highlighted on immunohistochemical study with CD79a, CD138 and EMA, and showed polyclonal immunoexpression of kappa and lambda immunoglobulin light chains. PMID- 20361886 TI - Laryngeal squamous cell carcinoma with knee and heel skin metastases: a case report. AB - Distant metastases from laryngeal carcinoma are frequently seen in the lung, bone and liver, while skin metastases are rarely observed. In these cases presented as case reports in the literature, the supradiaphragmatic region is usually involved. Skin metastasis in lower extremity has only been reported in a few cases. While being an indicator of poor prognosis, skin metastasis is also considered as a messenger of distant organ metastasis. Survival is very short after development of skin metastasis. In our case, nodular skin metastasis was found both in the superior-lateral margin of the left patella and in the right heel. This is the first case reported in the literature on laryngeal carcinoma metastasizing to these localizations. PMID- 20361887 TI - Multicentric reticulohistiocytosis with S100 protein positive staining: a case report. AB - Multicentric reticulohistiocytosis is a very rare systemic disease that affects skin, mucosa and joints. We reported a case of a woman with multicentric reticulohistiocytosis who presented typical skin syndromes and arthralgia. Immunohistochemical analysis showed positive staining for S100 protein, which was reported negative in the majority of previously presented cases. Other immunohistochemical markers (CD68(+), CD1a(-), lagerin (-) and complete histologic and clinical picture were specific enough to make the definitive diagnosis of multicentric reticulohistiocytosis. The patient was administered prednisone just when arthritis appeared and we believe that this therapy protected her from the development of destructive arthritis. No autoimmune disease or internal malignancy was observed during 12-month follow up. PMID- 20361888 TI - Role and significance of atopy patch test. AB - Atopic eczema/dermatitis syndrome (AEDS) is a chronic, intermittent, inflammatory, genetically predisposed skin disease characterized by severe pruritus and xerosis. AEDS is a common disorder in children with an increasing prevalence. A number of environmental factors have been implicated in the pathogenesis of AEDS. Atopy patch test (APT) is a patch test using type Iota allergens known to elicit IgE mediated reactions. Results are evaluated after 48 and 72 h. APT has been recognized as a useful diagnostic tool in the diagnosis of delayed type of reaction in AEDS since specific IgE (sIgE) and skin prick test (SPT) can be only correlated with early reactions. Standardized technique has been proposed by the European Task Force on Atopic Dermatitis. It consists of purified allergen preparation in petrolatum, applied in 12 mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin on the upper back. Optimal results were obtained with petrolatum, in aeroallergen concentration over 5000 PNU. Food allergy takes place in the first years of life, while the role of aeroallergens becomes more significant in older children and adults. A common scenario is development of allergy to cow's milk early in life, usually accompanied by allergy to hen's egg and wheat. Up to 3 years of age, the child usually becomes tolerant to food and sensitization to one of multiple aeroallergens occurs. The children that will develop clinically relevant reactions to food may benefit from elimination diets. APT has been recognized as a diagnostic tool in food allergy evaluation, but its role remains controversial and double blind placebo controlled food challenge remains the gold standard. It has a role in the detection of gastrointestinal manifestations of allergy and in eosinophilic esophagitis. When the symptoms occur at air-exposed sites, the role of aeroallergens is possible. Today, the most commonly used aeroallergens are house dust mite, pollen and animal dander. PMID- 20361889 TI - Adverse cutaneous reactions to psychopharmaceuticals. AB - Adverse cutaneous reactions to psychoactive drugs are common. They disturb and interrupt therapy often leading to non-compliance. The majority of adverse cutaneous reactions are benign if they are promptly recognized. Withdrawal of suspected drug is the first step for consequent treatment. As some adverse cutaneous reactions are life threatening, the most important action is to discontinue the drug usage promptly, thus minimizing morbidity. It is very important for physicians to be aware of the potentially serious adverse skin reactions to psychoactive drugs. Patients must be provided with simple information on these adverse effects. PMID- 20361890 TI - Function association of tissue inhibitor of metalloproteinase-1 and malignant melanoma: systomics approach. PMID- 20361894 TI - Neural processing of emotional overinvolvement in borderline personality disorder. AB - OBJECTIVE: Patients with borderline personality disorder (BPD) fare better clinically if their families are rated as being high in emotional overinvolvement, which is characterized by marked emotionality, anxious concern, and protective behavior. This is not true of patients with disorders such as schizophrenia or major depression. We used functional magnetic resonance imaging methods to explore the link between emotional overinvolvement (EOI) and better clinical outcome in BPD. Specifically, we tested the hypothesis that, unlike healthy controls or people with other psychiatric problems, people with BPD process EOI as an approach-related stimulus. METHOD: Participants with BPD (n = 13) and dysthymia (n = 10) (DSM-IV criteria for both) and healthy controls (n = 11) were imaged using a high field strength (3T) scanner while they listened to a standardized auditory stimulus consisting of either 4 neutral or 4 EOI comments. Participants also rated their mood before and after exposure to the comments. RESULTS: All participants reported increased negative mood after hearing EOI and rated the EOI comments as negative stimuli. However, after subtracting activation to neutral comments, participants with BPD showed higher activation in left prefrontal regions during EOI compared to the other groups. Increased left prefrontal activation during EOI was also correlated with clinical measures indicative of borderline pathology. Participants with dysthymia showed increased amygdala activation during EOI. This was not true for the healthy controls or participants with BPD. CONCLUSIONS: For people with BPD, EOI may be activating neural circuitry implicated in the processing of approach-related stimuli. Increased left prefrontal activation to EOI may be a vulnerability marker for BPD. These findings may also help explain why BPD patients do better clinically in high EOI family environments. PMID- 20361895 TI - Lithium treatment effects on the neuropsychological functioning of patients with bipolar I disorder. AB - OBJECTIVE: To determine if medication plays a major role in cognitive impairment in bipolar disorder and if regular treatment with lithium influences the cognitive performance of a group of euthymic patients with bipolar I disorder. METHOD: Cognitive performance was assessed using neuropsychological tests of attention, memory, and executive function on 60 subjects: 20 euthymic bipolar I patients with no medication intake, 20 euthymic bipolar I patients who were following regular treatment with lithium carbonate monotherapy, and a third group of 20 control healthy subjects. The subjects were evaluated from January 2005 to October 2006. Patients were diagnosed using DSM-IV criteria for bipolar disorder. RESULTS: Compared to the healthy group, bipolar I patients had significantly lower performance on episodic verbal and visual-verbal memory regardless of their medication status. No significant cognitive performance differences were found between the two groups of patients with bipolar disorder, suggesting that lithium therapy had no deleterious effects on cognition. CONCLUSION: Patients with bipolar I disorder have verbal memory deficits that are not explained by medication or by lithium monotherapy, but by the condition itself. PMID- 20361896 TI - Causes of aggressive behavior in patients with dementia. AB - OBJECTIVE: To examine factors predicting development of aggression. METHOD: Community-dwelling patients over 60 years of age in a Veterans Affairs Medical Center who had a documented ICD-9-CM code for dementia within 12 months of screening and no other dementia codes recorded for 2 preceding years but no aggressive behavior during the 12 months preceding study initiation were assessed every 4 months for 24 months for aggression, depression, pain, patient/caregiver relationship quality (mutuality), involvement in pleasant events, and caregiver burden. The study was conducted from September 5, 2003, to June 10, 2005. RESULTS: Of 215 patients, 89 (41%) developed aggression. In individual models, high baseline mutuality decreased risk of aggression; high burden and pain increased risk. Increases in depression and pain and declines in total mutuality also increased risk. In a full model and step-wise model, high levels of baseline caregiver burden, worst pain, and decline in mutuality over time increased risk of aggression. CONCLUSIONS: Many dementia patients become aggressive. Higher levels of worst pain, caregiver burden, and declining mutuality over time increase risk of aggression. PMID- 20361897 TI - Positron emission tomography measurement of dopamine D2 receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. AB - OBJECTIVE: Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics. METHOD: In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [11C]FLB 457 was performed on all subjects. The dopamine D2receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D2receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007. RESULTS: Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D2receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D2receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61). CONCLUSIONS: Dopamine D2receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose. PMID- 20361898 TI - Clinical and ethical considerations in pharmacogenetic testing: views of physicians in 3 "early adopting" departments of psychiatry. AB - OBJECTIVE: Pharmacogenetic testing for polymorphisms affecting drug response and metabolism is now clinically available, and its use in psychiatry is expected to become more widespread. Currently, few clinical and ethical standards exist for the use of these new tests. As a step toward building consensus about testing, we assessed the attitudes and practices of psychiatrists at 3 academic departments of psychiatry where pharmacogenetic testing is clinically available. We hypothesized that testing would be used primarily in treatment-resistant illness and that clinicians would believe such tests carried little risk. METHOD: Residents and faculty at 3 departments of psychiatry considered to be "early adopters" of pharmacogenetic testing were invited during the academic year 2006 2007 to complete an Internet-based survey, including questions regarding clinical practices and opinions about testing utility, risks, and necessary safeguards. RESULTS: The 75 respondents had ordered pharmacogenetic testing a mean of 20.86 times in the previous 12 months. Testing was judged most useful in cases of treatment-resistant depression and medication intolerance. There was a lack of consensus about the risks of testing, particularly the risk of secondary information about disease susceptibility. Respondents endorsed the use of several safeguards, including confidentiality, pretest and posttest counseling, and informed consent, but consensus about other safeguards was lacking. Women and those who had not ordered testing in the prior year were more concerned about risks and need for safeguards than were men and those who had recently ordered testing. CONCLUSIONS: Physicians at early adopting departments of psychiatry endorsed the clinical utility of pharmacogenetic testing and the use of some patient safeguards, but showed a lack of consensus about other safeguards and risks. PMID- 20361899 TI - Prevalence and correlates of fire-setting in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). AB - OBJECTIVE: To estimate the prevalence, sociodemographic correlates, comorbidity, and rates of mental health service utilization of fire-setters in the general population. METHOD: A face-to-face survey of more than 43,000 adults aged 18 years and older residing in households was conducted during the 2001-2002 period. Diagnoses of mood, anxiety, substance use disorders, and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). RESULTS: The prevalence of lifetime fire setting in the US population was 1.13 (95% CI, 1.0-1.3). Being male, never married, and US-born and having a yearly income over $70,000 were risk factors for lifetime fire-setting, while being Asian or Hispanic and older than 30 years were protective factors for lifetime fire-setting. The strongest associations with fire-setting were with disorders often associated with deficits in impulse control, such as antisocial personality disorder (ASPD) (odds ratio [OR] = 21.8; CI, 6.6-28.5), drug dependence (OR = 7.6; 95% CI, 5.2-10.9), bipolar disorder (OR = 5.6; 95% CI, 4.0-7.9), and pathological gambling (OR = 4.8; 95% CI, 2.4-9.5). Associations between fire-setting and all antisocial behaviors were positive and significant. A lifetime history of fire-setting, even in the absence of an ASPD diagnosis, was strongly associated with substantial rates of Axis I comorbidity, a history of antisocial behavior, a family history of other antisocial behaviors, decreased functioning, and higher treatment-seeking rates. CONCLUSIONS: Our findings suggest that fire-setting may be better understood as a behavioral manifestation of a broader impaired control syndrome and part of the externalizing spectrum. Fire-setting and other antisocial behaviors tend to be strongly associated with each other and increase the risk of lifetime and current psychiatric disorders, even in the absence of a DSM-IV diagnosis of ASPD. PMID- 20361900 TI - Moderators and mediators of symptoms and quality of life outcomes in an open label study of adults treated for attention-deficit/hyperactivity disorder. AB - OBJECTIVE: The Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) study was designed to evaluate effectiveness of long-acting amphetamines in adults with attention-deficit/hyperactivity disorder (ADHD) in community practice settings. This article reports moderators and mediators of symptoms and quality of life outcomes. METHOD: This was an open-label study of 725 adults with DSM-IV-diagnosed ADHD, treated with mixed amphetamine salts extended release and followed for up to 8 months. Multiple regressions were used to determine if patient moderators impact response in ADHD symptoms and how ADHD symptoms and medication satisfaction mediate quality of life. The study was conducted from December 2003 to December 2004. RESULTS: Amphetamine treatment of ADHD resulted in a robust and enduring symptom response. Patient characteristics such as age, female gender, severity of illness, and treatment-naive status moderate improved symptom outcome. Symptom change and satisfaction with medication independently mediate change in mental but not physical quality of life outcomes. There is no time lag between changes in symptoms and improved quality of life. Attention is a stronger mediator of ADHD-specific quality of life outcomes than disruptive behavior. CONCLUSIONS: If symptoms and quality of life improve simultaneously, improvement in quality of life can be understood as more than just a downstream, secondary effect of symptom remission. Satisfaction with medication is a direct measure of the complex interplay of symptom change, tolerability, and patient perception of treatment that predicts self-report of quality of life benefits. Although the disruptive symptoms of ADHD are more obvious, adults self-report that attention has greater impact. PMID- 20361901 TI - Randomized, double-blind, placebo-controlled study of divalproex extended release loading monotherapy in ambulatory bipolar spectrum disorder patients with moderate-to-severe hypomania or mild mania. AB - OBJECTIVE: To determine whether divalproex extended release (ER) would be effective in outpatients with DSM-IV-TR-diagnosed ambulatory bipolar spectrum disorder (BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania). METHOD: An 8-week, randomized, double-blind, placebo controlled trial of divalproex ER oral loading (begun at 15 mg/kg/d and titrated to a maximum of 30 mg/kg/d) in ambulatory BSD with hypomania/mild mania patients, operationally defined as a Young Mania Rating Scale (YMRS) score >or= 10 but < 21 at baseline and at 1 other study visit at least 3 days apart over the 2 weeks before baseline, was conducted. Patients were enrolled from October 2003 through November 2007. RESULTS: Sixty patients (n = 30 in the divalproex ER group) had at least 1 postbaseline assessment. The divalproex ER group showed a significantly greater rate of reduction in mean total YMRS score than the placebo group (longitudinal analysis, P = .024). The divalproex ER group also showed more improvement in depressive symptoms the greater the severity of baseline depression (P = .11 for analysis of covariance treatment-by-baseline interaction). Baseline-to-endpoint change scores using last-observation-carried forward showed that divalproex ER was associated with a marginally significant change in mean total YMRS score (P = .080). Comparable numbers of patients discontinued divalproex ER (n = 17) and placebo (n = 15), including those that discontinued use because of adverse events (n = 4 and 3, respectively). CONCLUSIONS: Divalproex ER begun at 15 mg/kg/d was superior to placebo in reducing hypomanic/mild manic symptoms in ambulatory BSD. It was associated with fairly good tolerability but a high discontinuation rate. Controlled trials of divalproex ER and other mood stabilizers in larger groups of ambulatory BSD patients with hypomanic/mild manic symptoms appear warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00278772. PMID- 20361902 TI - Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. AB - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a safe treatment method with few side effects. However, efficacy for various psychiatric disorders is currently not clear. DATA SOURCES: A literature search was performed from 1966 through October 2008 using PubMed, Ovid Medline, Embase Psychiatry, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and PsycINFO. The following search terms were used: transcranial magnetic stimulation, TMS, repetitive TMS, psychiatry, mental disorder, psychiatric disorder, anxiety disorder, attention deficit hyperactivity disorder, bipolar disorder, catatonia, mania, depression, obsessive-compulsive disorder, psychosis, posttraumatic stress disorder, schizophrenia, Tourette's syndrome, bulimia nervosa, and addiction. STUDY SELECTION: Data were obtained from randomized, sham-controlled studies of rTMS treatment for depression (34 studies), auditory verbal hallucinations (AVH, 7 studies), negative symptoms in schizophrenia (7 studies), and obsessive compulsive disorder (OCD, 3 studies). Studies of rTMS versus electroconvulsive treatment (ECT, 6 studies) for depression were meta-analyzed. DATA EXTRACTION: Standardized mean effect sizes of rTMS versus sham were computed based on pretreatment-posttreatment comparisons. DATA SYNTHESIS: The mean weighted effect size of rTMS versus sham for depression was 0.55 (P < .001). Monotherapy with rTMS was more effective than rTMS as adjunctive to antidepressant medication. ECT was superior to rTMS in the treatment of depression (mean weighted effect size 0.47, P = .004). In the treatment of AVH, rTMS was superior to sham treatment, with a mean weighted effect size of 0.54 (P < .001). The mean weighted effect size for rTMS versus sham in the treatment of negative symptoms in schizophrenia was 0.39 (P = .11) and for OCD, 0.15 (P = .52). Side effects were mild, yet more prevalent with high-frequency rTMS at frontal locations. CONCLUSIONS: It is time to provide rTMS as a clinical treatment method for depression, for auditory verbal hallucinations, and possibly for negative symptoms. We do not recommend rTMS for the treatment of OCD. PMID- 20361903 TI - Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients. AB - OBJECTIVE: The present study aimed (1) to determine the proportion of patients treated with persistent antipsychotic polypharmacy in an outpatient population and (2) to determine if persistent antipsychotic polypharmacy is associated with excessive dosing. METHOD: Using a province-wide network that links all pharmacies in British Columbia, Canada, to a central set of data systems, we identified community mental health outpatients who had been treated with the same pharmacologic regimen for at least 90 days. Apart from antipsychotics, data collection included anticholinergics, antidepressants, mood stabilizers, benzodiazepines, lipid-lowering agents, and antidiabetic agents. Demographic data including sex, age, and diagnosis were obtained from the patient's chart. In order to compare dosages of the various antipsychotics we used a fixed unit of measurement based on dividing the prescribed daily dose (PDD) by the defined daily dose (DDD). A PDD/DDD ratio greater than 1.5 was defined as excessive dosing. RESULTS: Four hundred thirty-five patients met the inclusion criteria and were included in the analysis. Overall, the prevalence of persistent antipsychotic polypharmacy was 25.7% for the entire cohort. The prevalence of persistent antipsychotic polypharmacy was highest for patients with schizoaffective disorder (33.7%), followed by schizophrenia (31.7%), psychosis not otherwise specified (20.0%), bipolar disorder (16.9%), and major depression (14.3%). The mean +/- SD PDD/DDD ratio for all patients prescribed persistent antipsychotic polypharmacy was not only excessive, it was significantly greater compared to that of patients receiving antipsychotic monotherapy (1.94 +/- 0.12 vs 0.94 +/- 0.04, P < .005). CONCLUSIONS: Using a diagnostically heterogeneous outpatient population, this study is, we believe, the first to report that persistent antipsychotic polypharmacy is associated with excessive dosing, in and of itself as well as compared to antipsychotic monotherapy. PMID- 20361904 TI - A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the acute treatment of mania. AB - OBJECTIVE: Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here. METHOD: A total of 225 DSM-IV-diagnosed bipolar I disorder patients were randomly assigned in a 2:1 ratio to 21 days of double-blind treatment with divalproex ER (n = 147) or placebo (n = 78). The daily divalproex ER dosage was initiated at 20 mg/kg. The primary efficacy variable was the change from baseline to final evaluation in Mania Rating Scale (MRS) score. Subjects were discontinued from the study if they were discharged from the hospital or if they met prespecified improvement criteria. The study was conducted from May 1998 to July 1999 at centers in the United States. RESULTS: There was no statistically significant difference in MRS score change from baseline to final for patients treated with divalproex ER compared with those treated with placebo. With the exception of back pain and constipation, adverse event rates between placebo and divalproex ER were very similar. A large proportion of patients prematurely discontinued study treatment (divalproex ER: 83%, placebo: 82%). The mean daily dose of divalproex ER was 2,211 mg with a mean maximum serum valproic acid concentration of 77.9 microg/mL. CONCLUSIONS: The results of the current study did not demonstrate statistically significant improvement in mania symptoms associated with divalproex ER treatment compared to placebo. A number of methodological considerations may have contributed to the negative findings, including allowance for early study discontinuation and lower than optimal dosing. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00060905. PMID- 20361905 TI - Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies. AB - OBJECTIVE: To characterize response profiles of olanzapine/fluoxetine combination therapy in treatment-resistant depression (TRD) and to investigate predictive relationships of early improvement with olanzapine/fluoxetine combination for subsequent response/remission during the acute phase of treatment. METHOD: Results were pooled from 5 outpatient studies comparing oral olanzapine/fluoxetine combination, fluoxetine, or olanzapine for a maximum of 8 weeks in patients with TRD who had at least 1 historical antidepressant treatment failure during the current episode and who failed a prospective antidepressant therapy during the study lead-in period. Mean Montgomery-Asberg Depression Rating Scale (MADRS) total and core mood items scores from the 8-week evaluation period were compared across treatment groups. Positive and negative predictive values (PPVs, NPVs) were computed from olanzapine/fluoxetine combination-treated patients demonstrating response and remission based on whether they demonstrated early improvement. RESULTS: Mean olanzapine/fluoxetine combination MADRS score reductions were significantly greater than fluoxetine by week 0.5 and olanzapine by week 1. Significantly more olanzapine/fluoxetine combination patients demonstrated MADRS onset of response compared with fluoxetine and olanzapine patients (P < .001 for both MADRS total and core mood items). In olanzapine/fluoxetine combination patients, 38.1% exhibited MADRS total score response versus 26.9% of fluoxetine patients (P < .001) and 22.2% of olanzapine patients (P < .001). NPVs for MADRS total and core mood items response and remission ranged from 85.7% to 92.1%; PPVs ranged from 29.9% to 45.1%. CONCLUSIONS: Olanzapine/fluoxetine combination is superior to fluoxetine and olanzapine in producing early improvement in patients with TRD. The absence of early improvement is highly predictive for overall response failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00035321. PMID- 20361906 TI - Does the therapy manual or the therapist matter most in treatment of obsessive compulsive disorder? A randomized controlled trial of exposure with response or ritual prevention in 118 patients. AB - BACKGROUND: The importance of the therapist's education and experience for the successful behavior treatment of obsessive-compulsive disorder (OCD) has not been investigated. Data on the relative effectiveness of self-controlled versus therapist-controlled in vivo exposure with response or ritual prevention (ERP) have yielded conflicting results. The present study compared the effectiveness of 4 different modes of delivery of ERP in a referred sample of OCD patients. METHOD: Of the 146 eligible OCD outpatients, 118 patients enrolled in this randomized controlled trial and were randomly assigned to (1) therapist controlled ERP performed by experienced behavior therapists; (2) therapist controlled ERP performed by master's students of clinical psychology; (3) self controlled ERP performed by experienced behavior therapists; and (4) self controlled ERP performed by master's students of clinical psychology. This trial was performed from January 1999 to January 2005. RESULTS: Our analyses revealed no significant differences in clinical outcome between any of the different modes of delivery of ERP at posttreatment. The different ERP modes of delivery were associated with significant pretreatment to posttreatment improvement on all measurements, with large effect sizes on the primary outcome measure, the Yale Brown Obsessive Compulsive Scale. CONCLUSIONS: Our results indicate that clinically inexperienced master's students with no postgraduate training can be as capable as experienced and certified behavior therapists in treating OCD patients, as long as therapists adhere to a standardized treatment manual and adequate training and supervision is provided. In contrast to other studies, we did not find a supposed benefit of therapist-controlled ERP versus self controlled ERP in patients with OCD. TRIAL REGISTRATION: www.trialregister.nl Identifier: NTR1444. PMID- 20361907 TI - Neurocognitive functioning in patients with bipolar I disorder recently recovered from a first manic episode. AB - OBJECTIVE: Although cognitive impairment is an important clinical feature of bipolar disorder, it is unknown whether deficits are present at illness onset. The purpose of this study was to determine whether neuropsychological impairments are present in clinically stable patients with bipolar disorder shortly after resolution of their first manic episode. METHOD: Within a large university medical center, 45 recently diagnosed (DSM-IV-TR) patients with bipolar disorder type I were evaluated after resolution of their first manic episode, along with 25 matched healthy comparison subjects. Participants were administered a neuropsychological battery evaluating 5 broad cognitive domains, including verbal/premorbid intellectual functioning, learning/memory, spatial/nonverbal reasoning, attention/processing speed, and executive function. Data were collected from July 2004 to August 2007. RESULTS: Relative to controls, patients showed broad impairments in learning/memory, spatial/nonverbal reasoning, executive function, and some aspects of attention (all P < .01). Specifically, deficits were evident on tests assessing sustained attention, attentional and mental set shifting, spatial working memory, nonverbal reasoning, and verbal learning and recall (all P < .01). Cognitive impairments in patients could not be fully attributed to substance abuse, medication status, or residual mood symptoms. CONCLUSIONS: Results indicate that core neuropsychological deficits in sustained attention, learning and recall, spatial/nonverbal reasoning, and several aspects of executive function are present at illness onset. Cognitive deficits in bipolar disorder are, thus, most likely not exclusively attributable to progressive decline associated with increased illness burden, cumulative treatment effects, or chronicity of illness. These findings may provide etiologic clues into the illness and identify clinical targets for early treatment. PMID- 20361908 TI - Topiramate in the treatment of substance-related disorders: a critical review of the literature. AB - OBJECTIVE: To critically review the literature on topiramate in the treatment of substance-related disorders. DATA SOURCES: A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines. STUDY SELECTION: 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines. DATA EXTRACTION: Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. DATA SYNTHESIS: There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse. CONCLUSIONS: Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies. PMID- 20361909 TI - Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: review and meta-analysis. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for the negative symptoms of schizophrenia. During the past decade, several trials have reported on the efficacy of rTMS treatment; however, the results were inconsistent. OBJECTIVE: To assess the efficacy of prefrontal rTMS for treating negative symptoms of schizophrenia. DATA SOURCES: A literature search was performed in PubMed, ISI Web of Science, and EMBASE for the years 1985 through July 2008. The search terms used (language not specified) were "transcranial magnetic stimulation," "negative symptoms," and "schizophrenia." A cross-reference search of eligible articles was performed to identify studies not found in the computerized search. STUDY SELECTION: Studies selected were randomized controlled trials assessing the therapeutic efficacy of prefrontal rTMS for negative symptoms in schizophrenia. DATA EXTRACTION: Effect sizes (Cohen d) of each study were calculated. The overall standardized mean difference was calculated under a random effects model with 95% confidence intervals. DATA SYNTHESIS: Nine trials, involving 213 patients, were included in the meta analysis. The overall mean weighted effect size for rTMS versus sham was in the small-to-medium range and statistically significant (d = 0.43; 95% CI, 0.05 0.80). When including only the studies using a frequency of stimulation of 10 Hz, the mean effect size increased to 0.63 (95% CI, 0.11-1.15). When including only the studies requiring participants to be on a stable drug regimen before and during the study, the mean weighted effect size decreased to 0.34 (95% CI, 0.01 0.67). Studies with a longer duration of treatment (> or =3 weeks) had a larger mean effect size when compared to studies with a shorter treatment duration: d = 0.58 (95% CI, 0.19-0.97) and d = 0.32 (95% CI, -0.3 to 0.95), respectively. CONCLUSIONS: The results of this meta-analysis warrant further study of rTMS as a potential treatment of negative symptoms of schizophrenia. PMID- 20361910 TI - Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls. AB - OBJECTIVE: To analyze cases of clozapine-induced myocarditis for clinical and diagnostic trends. METHOD: A case definition was developed by a multidisciplinary group using reports of myocarditis with clozapine submitted to the Australian Therapeutic Goods Administration. The definition uses for diagnosis either histology or the combination of new signs of cardiac dysfunction combined with a cardiac-specific diagnostic parameter occurring within 45 days of starting clozapine. Potential cases of clozapine-related myocarditis occurring between January 1993 and September 2008 and a comparative group of long-term clozapine users were documented from the patients' medical records. RESULTS: Thirty-eight of 59 reviewed cases met the case definition. Three patients died, and the diagnosis for these was confirmed on cardiac histology. Nearly all of the remaining patients had persistent tachycardia and elevated troponin level. The time to onset was 14-22 days in all except 2 patients. Of the patients who survived, 66% (23 cases) had eosinophilia occurring 0-7 days (mean, 4.0) after the peak in troponin. C-reactive protein (CRP) level was elevated to above 100 mg/L (952 nmol/L) in 79% (23 cases), and some had elevated levels of CRP when troponin level was still normal. None of the control group (47 patients) met the case definition. CONCLUSIONS: Eosinophil counts should not be relied on for diagnosis of clozapine-related myocarditis, but elevated CRP may be an early indicator of developing myocarditis. Patients starting clozapine should be actively monitored for myocarditis during the first 4 weeks, with extra care taken during week 3. PMID- 20361911 TI - Assertive community treatment as part of integrated care versus standard care: a 12-month trial in patients with first- and multiple-episode schizophrenia spectrum disorders treated with quetiapine immediate release (ACCESS trial). AB - OBJECTIVE: The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release. METHOD: Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care (n = 64) or standard care (n = 56) to 120 patients with first- or multiple episode schizophrenia spectrum disorders (Structured Clinical Interview for DSM IV Axis I Disorders criteria); multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence. The primary outcome was time to service disengagement. Secondary outcomes comprised medication nonadherence, improvements of symptoms, functioning, quality of life, satisfaction with care from patients' and relatives' perspectives, and service use data. The study was conducted from April 2005 to December 2008. RESULTS: 17 of 120 patients (14.2%) disengaged with service, 4 patients (6.3%) in the ACT and 13 patients (23.2%) in the standard care group. The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group (95% CI, 49.1-52.0) and 44.1 weeks in the standard care group (95% CI, 40.1-48.1). This difference was statistically significant (P = .0035). Mixed models repeated measures indicated larger improvements for ACT compared to standard care regarding symptoms (P < . 01), illness severity (P < . 001), global functioning (P < . 05), quality of life (P < . 05), and client satisfaction as perceived by patients and family (both P < . 05). Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied (P = .001), of living independently (P = .007), and of being adherent with medication (P < . 001) and a lower likelihood of persistent substance misuse (P = .027). CONCLUSIONS: Compared to standard care, intensive therapeutic ACT as part of integrated care could improve 1-year outcome. Future studies need to address in which settings these improvements can be sustained. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01081418. PMID- 20361913 TI - Screening for bipolar disorder and finding borderline personality disorder. AB - OBJECTIVE: Bipolar disorder and borderline personality disorder share some clinical features and have similar correlates. It is, therefore, not surprising that differential diagnosis is sometimes difficult. The Mood Disorder Questionnaire (MDQ) is the most widely used screening scale for bipolar disorder. Prior studies found a high false-positive rate on the MDQ in a heterogeneous sample of psychiatric patients and primary care patients with a history of trauma. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined whether psychiatric outpatients without bipolar disorder who screened positive on the MDQ would be significantly more often diagnosed with borderline personality disorder than patients who did not screen positive. METHOD: The study was conducted from September 2005 to November 2008. Five hundred thirty-four psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV and Structured Interview for DSM-IV Personality Disorders and asked to complete the MDQ. Missing data on the MDQ reduced the sample size to 480. Approximately 10% of the study sample were diagnosed with a lifetime history of bipolar disorder (n = 52) and excluded from the initial analyses. RESULTS: Borderline personality disorder was 4 times more frequently diagnosed in the MDQ positive group than the MDQ negative group (21.5% vs 4.1%, P < .001). The results were essentially the same when the analysis was restricted to patients with a current diagnosis of major depressive disorder (27.6% vs 6.9%, P = .001). Of the 98 patients who screened positive on the MDQ in the entire sample of patients, including those diagnosed with bipolar disorder, 23.5% (n = 23) were diagnosed with bipolar disorder, and 27.6% (n = 27) were diagnosed with borderline personality disorder. CONCLUSIONS: Positive results on the MDQ were as likely to indicate that a patient has borderline personality disorder as bipolar disorder. The clinical utility of the MDQ in routine clinical practice is uncertain. PMID- 20361912 TI - Why do clinicians maintain antidepressants in some patients with acute mania? Hints from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a large naturalistic study. AB - OBJECTIVE: Antidepressants are supposed to be withdrawn during a manic episode. The aim of this study was to analyze the characteristics of manic patients who received antidepressants during a manic phase in a large, naturalistic study. METHOD: The European Mania in Bipolar Longitudinal Evaluation of Medication was a 2-year prospective observational study of inpatients and outpatients with acute mania/mixed mania (DSM-IV or ICD-10 criteria) conducted in 14 European countries. Of 2,416 manic patients who continued into the maintenance phase of the study, 345 (14%) were taking an antidepressant and 2,071 (86%) were not taking an antidepressant at baseline, week 1, and/or week 2 postbaseline. Demographic and clinical variables were collected at baseline and each study visit up to 24 months. Outcome measures included the Clinical Global Impressions-Bipolar Disorder scale (CGI-BP overall, mania, and depression scores) at 12 weeks and 24 months, the 5-item Hamilton Depression Rating Scale (HDRS-5), and the Young Mania Rating Scale (YMRS) at 12 weeks only. The present study was conducted from December 2002 to June 2004. RESULTS: More antidepressant maintenance use was seen in patients with mixed episodes (P < .001), rapid cyclers (P < .02), patients with more previous depressive episodes (P < .001), and patients with higher mean HDRS-5 score at baseline (P < .001)-specifically patients with anxiety (P = .013). Patients in the antidepressant group had significantly higher CGI-BP depression scores (P < .001) and a significantly higher rate of depression relapse (P < .001) at both 12 weeks and 24 months. CONCLUSIONS: Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up. PMID- 20361914 TI - A clinically useful anxiety outcome scale. AB - OBJECTIVE: Standardized scales are increasingly being recommended to measure outcome when treating psychiatric disorders in routine clinical practice. If the standard of care is to change and scales are to be incorporated into clinical practice, then it will be necessary to develop measures that are feasible to use as well as have good psychometric properties. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we describe the reliability and validity of the Clinically Useful Anxiety Outcome Scale (CUXOS). The CUXOS was designed to be a brief (completed in less than 2 minutes), quickly scored (in less than 15 seconds), clinically useful measure that is reliable, valid, and sensitive to change. METHOD: Nearly 1,000 psychiatric outpatients completed the CUXOS and were rated on clinician severity indices of depression, anxiety, and anger. A subset of patients completed other self-report symptom severity scales in order to examine discriminant and convergent validity, and a subset completed the CUXOS twice in order to examine test-retest reliability. Sensitivity to change was examined in patients with panic disorder and generalized anxiety disorder. RESULTS: On average, the CUXOS took less than 1.5 minutes to complete. The scale had high internal consistency and test-retest reliability, and was more highly correlated with other self report measures of anxiety than with measures of depression, substance use problems, eating disorders, and anger. The CUXOS was more highly correlated with clinician severity ratings of anxiety than with depression and anger, and CUXOS scores were significantly higher in psychiatric outpatients with anxiety disorders than in patients with other psychiatric disorders. Finally, the CUXOS was a valid measure of symptom change. CONCLUSIONS: The results of this large validation study of the CUXOS show that it is a reliable and valid measure of anxiety that is feasible to incorporate into routine clinical practice. PMID- 20361915 TI - Auditory pseudohallucinations in United Kingdom war veterans and civilians with posttraumatic stress disorder. AB - OBJECTIVE: Hearing voices is a little-known feature of posttraumatic stress disorder (PTSD), mainly reported in US war veterans; it may be better conceived of as a dissociative than as a psychotic phenomenon. We investigated this feature in a pair of studies: Study 1 tested whether hearing voices was also reported by United Kingdom war veterans and whether it was associated with other dissociative reactions. Study 2 tested whether reports of hearing voices would generalize to a civilian sample, evaluated whether it was specific to PTSD or could be explained by trauma exposure alone, and investigated its phenomenological characteristics in more detail. METHOD: Study 1, which was conducted from 2005 to 2008 at numerous sites in the United Kingdom, contrasted male war veterans with current PTSD, past PTSD, and no PTSD on measures of dissociation and hearing voices. Study 2, which was conducted from 2004 to 2008 in London, United Kingdom, compared hearing voices in civilian patients with PTSD, healthy controls exposed to trauma, and depressed patients. RESULTS: Study 1 showed that more veterans with current or past PTSD than no PTSD described hearing voices, which was related to other dissociative reactions. Study 2 confirmed that hearing voices was also present in a civilian sample, that it was specific to PTSD, and that it had the characteristics of a pseudohallucination. CONCLUSIONS: The results emphasize the dissociative nature of PTSD, identify a little-known symptom that causes considerable distress, and suggest new directions for the assessment and treatment of PTSD in military and civilian populations. PMID- 20361916 TI - Agomelatine in the treatment of major depressive disorder: an 8-week, multicenter, randomized, placebo-controlled trial. AB - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with moderate-to severe major depressive disorder (MDD) compared to placebo. METHOD: In this 8 week, multicenter, double-blind, parallel-group trial, patients with DSM-IV defined MDD were randomly assigned (1:1:1) to receive a once-daily dose of agomelatine 25 mg, agomelatine 50 mg, or placebo. The primary efficacy measure was the change from baseline to week 8 in the clinician-rated 17-item Hamilton Depression Rating Scale (HDRS(17)); other efficacy measures were the clinical remission and response rates (measured by HDRS(17)), Clinical Global Impressions scales, Hospital Anxiety and Depression Scale (HADS) score, subjective measures on sleep, and the overall quality of life. The study was conducted between December 2006 and January 2008. RESULTS: Agomelatine 25 mg/d was more efficacious based on the HDRS(17) total score (P = .01) compared to placebo throughout the treatment period, whereas for agomelatine 50 mg/d, statistically significant reduction in HDRS(17) total score could be observed from weeks 2 to 6 but not at week 8 (P = .144). A higher proportion of patients receiving agomelatine 25 mg/d showed clinical response (P = .013), clinical remission (P = .07), and improvement according to the Clinical Global Impressions-Improvement scale (P = .065) compared to those receiving placebo. No statistically significant difference between patients receiving agomelatine 50 mg/d compared to placebo on clinical response (P = .116) or clinical remission (P =. 457) was observed. HADS score, quality of sleep, and quality of life significantly improved with agomelatine 25 mg/d compared to placebo. Both agomelatine doses were safe and well tolerated, although clinically notable aminotransferase elevations were observed transiently in the agomelatine 50 mg/d group. CONCLUSIONS: Agomelatine 25 mg/d was effective in the treatment of patients with moderate-to-severe MDD and was safe and well tolerated. Agomelatine 50 mg/d provided evidence for its antidepressant efficacy until week 6 and was also safe and well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00411242. PMID- 20361917 TI - Intentional weight loss in overweight and obese patients with severe mental illness: 8-year experience of a behavioral treatment program. AB - OBJECTIVE: Obesity is 2 to 3 times more common among people with severe mental illness and has adverse effects on physical and psychological health. We report the experience from the first 8 years of a self-referring weight management clinic. METHOD: From 2000 to 2008, 113 patients with severe mental illness (according to ICD-10 criteria) with a mean +/- SE age of 43.8 +/- 1.7 years (range, 22-71 years) referred themselves to this clinic. The patients were seen in weekly group sessions lasting 1 hour that involved weight measurement, discussion, and education. The response to the program was assessed by the paired Student t test and linear analysis corrected for repeated measures. RESULTS: Mean +/- SE baseline weight was 90.1 +/- 1.6 kg (body mass index [BMI] = 32.2 +/- 0.5 kg/m(2)). Fifty subjects of the 142 total patient episodes (35%) dropped out within the first 3 months. Sixty-four subjects completed 1 year of the program, and 35 have attended for 2 years or longer. There were progressive statistically significant reductions in mean weight and BMI throughout the duration of monitoring, with no suggestion of a plateau. The mean +/- SE final weight loss was 7.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.42, P < .0001). CONCLUSIONS: Lifestyle advice within a group setting may be effective in long-term management of obese and overweight patients with severe mental illness. PMID- 20361918 TI - Augmentation with citalopram for suicidal ideation in middle-aged and older outpatients with schizophrenia and schizoaffective disorder who have subthreshold depressive symptoms: a randomized controlled trial. AB - OBJECTIVE: To examine the effects of citalopram augmentation of antipsychotics on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms. METHOD: In this placebo-controlled trial conducted from September 1, 2001, to August 31, 2007, 198 outpatients > or = 40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were randomly assigned to flexible-dose citalopram (n = 104) or placebo (n = 94) augmentation of their antipsychotic for 12 weeks. Depression was measured with the Hamilton Depression Rating Scale (HDRS) and Calgary Depression Rating Scale (CDRS). Primary suicidal ideation measures were the Clinical Global Impressions-Severity of Suicide scale (CGI-SS) and the InterSePT Scale for Suicidal Thinking (ISST); secondary outcomes were the Scale for Suicidal Ideation (SSI), Beck Hopelessness Scale (BHS), HDRS item 3, and CDRS item 8. RESULTS: Compared to placebo, at the final visit, citalopram was associated with lower BHS scores (4.21 vs 4.98; P < .05) and lower likelihood of having suicidal ideation on the ISST (17.7% vs 38.7%; P < .005) and HDRS item 3 (14.4% vs 22.6%; P < .05). Among the 114 participants with no baseline suicidal ideation, there were no significant differences between citalopram and placebo regarding "emergent" ideation on either primary outcome. Among the 55 participants with baseline suicidal ideation, fewer treated with citalopram had endpoint ideation on the ISST (28.6% vs 66.7%; P < .05). Significantly more depression responders than nonresponders went from having baseline suicidal ideation to no suicidal ideation on both the ISST (75.0% vs 31.4%; P < .05) and CGI-SS (84.6% vs 31.3%; P < .05). CONCLUSIONS: Treatment-emergent suicidal ideation was no more common with citalopram than placebo. In participants with baseline suicidal ideation, citalopram reduced suicidal ideation, especially in those whose depressive symptoms responded to treatment. PMID- 20361919 TI - Treatment effects of massage therapy in depressed people: a meta-analysis. AB - OBJECTIVE: To systematically investigate the treatment effects of massage therapy in depressed people by incorporating data from recent studies. DATA SOURCES: A meta-analysis of randomized controlled trials (RCTs) of massage therapy in depressed people was conducted using published studies from PubMed, EMBASE, PsycINFO, and CINAHL electronic database from inception until July 2008. The terms used for the search were derived from medical subheading term (MeSH) massage combined with MeSH depression. Hand searching was also checked for bibliographies of relevant articles. Retrieval articles were constrained to RCTs/clinical trials and human subjects. No language restrictions were imposed. STUDY SELECTION: We included 17 studies containing 786 persons from 246 retrieved references. Trials with other intervention, combined therapy, and massage on infants or pregnant women were excluded. DATA EXTRACTION: Two reviewers independently performed initial screen and assessed quality indicators by Jadad scale. Data were extracted on publication year, participant characteristics, and outcomes by another single reviewer. DATA SYNTHESIS: All trials showed positive effect of massage therapy on depressed people. Seventeen RCTs were of moderate quality, with a mean quality score of 6.4 (SD = 0.85). The pooled standardized mean difference in fixed- and random-effects models were 0.76 (95% CI, 0.61-0.91) and 0.73 (95% CI, 0.52-0.93), respectively. Both indicated significant effectiveness in the treatment group compared with the control group. The variance between these studies revealed possible heterogeneity (tau(2) = 0.06, Cochran chi-squared(16) = 25.77, P = .06). CONCLUSIONS: Massage therapy is significantly associated with alleviated depressive symptoms. However, standardized protocols of massage therapy, various depression rating scales, and target populations in further studies are suggested. PMID- 20361920 TI - High-resolution separation of tubulin monomers on polyacrylamide minigels. AB - High-resolution separation of alpha- and beta-tubulin by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) on minigels can be performed rapidly using simple modifications of the standard Laemmli procedure. Separation of the subunits can be observed even in high-protein loads (up to 40microg of protein). PMID- 20361921 TI - Allantoin in human urine quantified by ultra-performance liquid chromatography tandem mass spectrometry. AB - Uric acid is a potent antioxidant and scavenger of singlet oxygen and other radicals in humans. Allantoin, the predominant product of free radical-induced oxidation of uric acid, is efficiently excreted in the urine and has potential as a biomarker of oxidative stress. We developed a rapid and specific assay for urinary allantoin using ultra-performance liquid chromatography-tandem mass spectrometry suitable for high-throughput clinical studies. The method required minimal sample preparation and was accurate (mean error=6%), precise (intra- and interday imprecision <8%), and sensitive (limit of detection=0.06pmol). Allantoin levels measured in control samples were comparable to literature values. PMID- 20361922 TI - Analysis of testosterone and dihydrotestosterone in mouse tissues by liquid chromatography-electrospray ionization-tandem mass spectrometry. AB - A novel method was established for simultaneous quantitation of testosterone (T) and dihydrotestosterone (DHT) in murine tissue and serum samples. Endogenous T and DHT, together with the internal standards 17alpha-methyl-T and 17alpha-methyl DHT, were extracted from tissues and then derivatized by reaction with 2 hydrazino-4-(trifluoromethyl)-pyrimidine (HTP). Analysis by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) resulted in product ion spectra of HTP derivatives of both T and DHT that showed analyte specific fragmentations; the latter fragmentations were characterized by the use of high-resolution Orbitrap MS/MS. These specific fragmentations enabled quantitation of T and DHT in the multiple-reaction monitoring (MRM) mode. The method was validated with charcoal-stripped serum as the matrix. The lower limit of quantitation (LLOQ) was 0.10ng/ml for T and 0.50ng/ml for DHT. The method was then used for determination of serum and tissue levels of T and DHT in transgenic mice carrying a hypomorphic NADPH-cytochrome P450 reductase gene (Cpr-low mice). Remarkably, ovarian T levels in Cpr-low mice were found to be 25-fold higher than those in wild-type mice, a finding that at least partly explains the female infertility seen in the Cpr-low mice. In conclusion, our method provides excellent sensitivity and selectivity for determination of endogenous levels of T and DHT in mouse tissues. PMID- 20361923 TI - Quantification of folate in fruits and vegetables: A fluorescence-based homogeneous assay. AB - A high-throughput, homogeneous, fluorescence polarization, and fluorescence intensity assay has been developed for the measurement of folate in fruits and vegetables. This assay is based on the competitive displacement of the fluorescent folate ligands Alexa Fluor (Alexa) 594-folate and Alexa 660-folate from bovine milk folate-binding protein by folates in fruit and vegetable extracts. These fluorescent ligands are employed because their excitation and emission maxima are in regions of the spectrum with minimal autofluorescence in many extracts. Folate-binding protein and Alexa-folate were typically used at concentrations of 0.5 microg/ml and 5nM, respectively, in 20-microl volumes in 384-well microplates. The assay is complete within 100 min. The folate estimate is unaffected by the heterogeneity of polyglutamyl residues that complicates the liquid chromatography-mass spectrometry (LC-MS)-based methods of quantification. In this assay, folic acid had an apparent affinity 2.5-fold greater than 5 methyltetrahydrofolate (5MTHF); therefore, it cannot be used to quantify folate when both natural and synthetic folate are present. 5MTHF-equivalent values were measured in broccoli (240 microg/100g), strawberry (113 microg/100g), white grape (32 microg/100g), orange (44 microg/100g), tomato (12 microg/100g), raspberry (31 microg/100g), banana (29 microg/g), and kiwifruit (36 microg/100g). These data are similar to published values. However, the assay will not detect 5 formyltetrahydrofolate which is a significant constituent of the total folate in lettuce, spinach, carrot, and peppers. PMID- 20361924 TI - Almond (Prunus dulcis (Mill.) D.A. Webb) polyphenols: from chemical characterization to targeted analysis of phenolic metabolites in humans. AB - In this paper, a survey of our studies on almond polyphenols including their chemical characterization and further bioavailability in humans is reported. Combination of analytical techniques (LC-DAD/fluorescence, LC/ESI-MS and MALDI TOF-MS) allowed us, for the first time, the identification of A- and B-type procyanidin, propelargonidin and prodelphinidin polymers in almond skins. Glucuronide, O-methyl glucuronide, sulfate and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and isorhamnetin, and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones were detected in plasma and urine samples after the intake of almond skin polyphenols. In addition, numerous microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic and hydroxyhippuric acids were also identified. Depending of the type of metabolite, maximum urinary excretion was attained at different time in comparison to the control group in the course of the 24-h period of urine excretion, allowing us to establish the onset of microbial metabolism. PMID- 20361925 TI - (-)-Epigallocatechin-3-gallate inhibits Met signaling, proliferation, and invasiveness in human colon cancer cells. AB - The Met receptor tyrosine kinase is deregulated in a variety of cancers and is correlated with advanced stage and poor prognosis. Thus, Met has been identified as an attractive candidate for targeted therapy. We compared the tea polyphenol ( )-epigallocatechin-3-gallate (EGCG) and a specific Met inhibitor, SU11274, as suppressing agents of Met signaling in HCT116 human colon cancer cells. Treatment with hepatocyte growth factor increased phospho-Met levels, and this was inhibited in a concentration-dependent manner by EGCG and SU11274 (IC(50) 3.0 vs. 0.05muM, respectively). Downstream activation of Erk and Akt signaling pathways also was suppressed. Both compounds at a concentration of 5muM lowered cell viability and proliferation, with EGCG being more effective than SU11274, and the invasion of colon cancer cells in Matrigel assays was strongly inhibited. These findings are discussed in the context of the pleiotropic effects of tea catechins, their tissue metabolite levels, and the potential to inhibit colon cancer metastasis and invasion. PMID- 20361927 TI - Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl dopamine induced neurotoxicity. AB - Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-) epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids. PMID- 20361926 TI - NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. AB - NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) is a widely-distributed FAD dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes, at rates that are comparable with NADH or NADPH. These reductions depress quinone levels and thereby minimize opportunities for generation of reactive oxygen intermediates by redox cycling, and for depletion of intracellular thiol pools. NQO1 is a highly inducible enzyme that is regulated by the Keap1/Nrf2/ARE pathway. Evidence for the importance of the antioxidant functions of NQO1 in combating oxidative stress is provided by demonstrations that induction of NQO1 levels or their depletion (knockout, or knockdown) are associated with decreased and increased susceptibilities to oxidative stress, respectively. Furthermore, benzene genotoxicity is markedly enhanced when NQO1 activity is compromised. Not surprisingly, human polymorphisms that suppress NQO1 activities are associated with increased predisposition to disease. Recent studies have uncovered protective roles for NQO1 that apparently are unrelated to its enzymatic activities. NQO1 binds to and thereby stabilizes the important tumor suppressor p53 against proteasomal degradation. Indeed, NQO1 appears to regulate the degradative fate of other proteins. These findings suggest that NQO1 may exercise a selective "gatekeeping" role in regulating the proteasomal degradation of specific proteins, thereby broadening the cytoprotective role of NQO1 far beyond its highly effective antioxidant functions. PMID- 20361928 TI - Tea, flavonoids and stroke in man and mouse. AB - BACKGROUND AND PURPOSE: To evaluate the strength of the in vivo evidence of relationships between flavonoids and risk of stroke. METHODS: We reviewed the literature more broadly for flavonoids and stroke and conducted an evidence-based review of original publication experiments on tea or tea components on induced coronary occlusion in animal models and on the observational epidemiology on stroke and either tea or flavonoids in man. Each of the studies was evaluated by two independent reviewers. The evidence in total was compared with the Bradford Hill [1] and Stroke Therapy Academic Industry Roundtable (STAIR)(1) quality assessment criteria [2]. RESULTS: The search of epidemiologic publications revealed 7 cohort studies on flavonoid intake and stroke and 7 cohort studies and 3 case control studies on tea and stroke. In studies of tea there was a consistent protective effect. However, the epidemiologic research on flavonoids and stroke was much less consistent. Eleven animal experiments were identified that examined tea or tea components and stroke relevant sequelae, eight of which reported on infarct volume. All studies demonstrated reduced infarct volumes in animals exposed either to tea extracts, theanine or tea catechins prior to or shortly after reperfusion. CONCLUSIONS: Hill's criteria of causality are largely met in the case of tea and stroke. A high level of consistency across preclinical studies, of the effect of tea components as single agents effective in reducing stroke volume after middle cerebral artery occlusion, is noted in all rodent models (rat, mouse, and gerbil). Reductions in infarct volume are seen with both tea extracts consumed orally and tea components introduced intra-peritoneally. Observational epidemiology supports this finding in man for tea - the studies are consistent across countries and type of tea and the relative risks are moderately strong. That is not the case for the body of evidence on flavonoid intakes and stroke. PMID- 20361929 TI - AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of beta-catenin at Ser 552. AB - AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent studies show that AMPK involves in cell differentiation but the underlying mechanism remains undefined. Wingless Int-1 (Wnt)/beta-catenin signaling pathway regulates the differentiation of mesenchymal stem cells through enhancing beta-catenin/T-cell transcription factor 1 (TCF) mediated transcription. The objective of this study was to determine whether AMPK cross-talks with Wnt/beta-catenin signaling through phosphorylation of beta catenin. C3H10T1/2 mesenchymal cells were used. Chemical inhibition of AMPK and the expression of a dominant negative AMPK decreased phosphorylation of beta catenin at Ser 552. The beta-catenin/TCF mediated transcription was correlated with AMPK activity. In vitro, pure AMPK phosphorylated beta-catenin at Ser 552 and the mutation of Ser 552 to Ala prevented such phosphorylation, which was further confirmed using [gamma-(32)P]ATP autoradiography. In conclusion, AMPK phosphorylates beta-catenin at Ser 552, which stabilizes beta-catenin, enhances beta-catenin/TCF mediated transcription, expanding AMPK from regulation of energy metabolism to cell differentiation and development via cross-talking with the Wnt/beta-catenin signaling pathway. PMID- 20361930 TI - The frequency of KRAS mutation detection in human colon carcinoma is influenced by the sensitivity of assay methodology: a comparison between direct sequencing and real-time PCR. AB - PURPOSE: Kirsten rat sarcoma (KRAS) gene mutations occur early in the progression of colorectal adenoma to carcinoma. The mutation status of the KRAS gene determines the benefits of molecular targeting drugs in patients with advanced colorectal cancer, although many methods are available to detect such mutations. The purpose of this study was to evaluate the influence of assay sensitivity on the detection frequency of mutated genes. METHODS: Colorectal tumors in 224 colorectal cancer patients were characterized for KRAS mutations using PCR amplification following by direct sequencing as well as a peptide nucleic acid (PNA)-clamp real-time PCR-based assay. RESULTS: KRAS mutations were observed in 32.1% (72/224) patients by direct sequencing, and 43.3% (97/224) by PNA-clamp PCR. The chi-square test revealed that the difference in the frequency of KRAS mutations determined by direct sequencing and PNA-clamped PCR (threshold for 1% detection) was statistically significant (p<0.015). CONCLUSIONS: Our data suggest that assay method sensitivity clearly influences the detection frequency of mutated genes. As more sensitive assays detect more mutated genes in clinical samples, this must be taken into consideration when determining KRAS gene status in clinical practice. PMID- 20361931 TI - Mitochondrial autophagy protects against heat shock-induced apoptosis through reducing cytosolic cytochrome c release and downstream caspase-3 activation. AB - Autophagy is an evolutionarily conserved process for bulk degradation of cytoplasmic components, including large molecules and organelles. It can either help to enhance or to resist apoptosis, depending on the circumstances. The mechanism of how autophagy impacts apoptosis and the subsequent cellular events upon heat shock remains unclear. In this study, we demonstrate for the first time that mitochondrial membrane permeability transition (MPT)-sensitive mitochondrial autophagy can protect against heat-induced apoptosis through reduction of cytosolic cytochrome c release and downstream caspase-3 activation. With confocal microscopy, it was revealed that as autophagosomes increased, mitochondrial content was mass decreased after heat shock. Detailed analysis shows that a single swelling mitochondrion could be entrapped into autophagosome. The depolarization of mitochondria preceded the mitochondrial loss, and both could be abolished by MPT inhibitor cyclosporine (CsA). In addition, along with the decrease of mitochondrial content, the level of total cytochrome c was also reduced, resulting in a reduction of its release to cytoplasm. When heat shock was combined with 3-methyladenine (3-MA), an inhibitor of autophagy, the mitochondrial loss and the reduction of total cytochrome c were both inhibited, and then caspase-3 activation and cell apoptosis were increased. Thus, it is reasonable to believe that, heat shock-induced cellular events can be modulated by controlling autophagy, and this may represent a novel approach to enhance the efficacy of hyperthermia. PMID- 20361932 TI - Affinity purification of Candida albicans CaCdc4-associated proteins reveals the presence of novel proteins involved in morphogenesis. AB - Candida albicans CDC4 is nonessential and plays a role in suppressing filamentous growth, in contrast to its evolutionary counterparts involved in the G1-S transition of the cell cycle. Genetic epistasis analysis has indicated that proteins besides Sol1 are targets of C. albicans Cdc4. Moreover, no formal evidence suggests that C. albicans Cdc4 functions through the ubiquitin E3 ligase of the Skp1-Cul1/Cdc53-F-box complex. To elucidate the role of C. albicans CDC4, C. albicans Cdc4-associated proteins were sought by affinity purification. A 6xHis epitope-tagged C. albicans Cdc4 expressed from Escherichia coli was used in affinity purifications with the cell lysate of C. albicans cdc4 homozygous null mutant. Candida albicans Cdc4 and its associated proteins were resolved by SDS PAGE and visualized by silver staining. The candidate proteins were recovered and trypsin-digested to generate MALDI-TOF spectra profiles, which were used to search against those of known proteins in the database to reveal their identities. Two out of four proteins encoded by GPH1 and THR1 genes were further verified to interact with C. albicans Cdc4 using a yeast two-hybrid assay. We conclude that in vitro affinity purification using C. albicans Cdc4 generated from E. coli as the bait and proteins from cell lysate of C. albicans cdc4 homozygous null mutant as a source of prey permit the identification of novel proteins that physically interact and functionally associate with C. albicans Cdc4. PMID- 20361933 TI - Five mutations in N-terminus confer thermostability on mesophilic xylanase. AB - The termini of a pair of xylanases, one of mesophilic and one of thermophilic origin, was studied by molecular dissection and systematic mutagenesis. The thermostability of the mesophilic xylanase SoxB from Streptomyces olivaceovirdis was significantly improved by substituting its 33 N-terminal amino acid residues with the corresponding residues of the thermophilic xylanase TfxA from Thermomonospora fusca. Five amino acid substitutions, which clustered in one of the regions of the N-terminus, were discovered, for the first time, to account for the majority of the improvement in thermostability of SoxB. Further systematic mutagenesis and analysis of the five mutations demonstrated that comprehensive synergism of the five mutations was involved in conferring the thermostability on the SoxB. Moreover, when the five thermostabilizing mutations were introduced into two other G/11 xylanases, SlxB from Streptomyces lividans and AnxB from Aspergillus niger, their thermostabilities were also dramatically enhanced. PMID- 20361934 TI - Superposition of two tRNASer acceptor stem crystal structures: comparison of structure, ligands and hydration. AB - We solved the X-ray structures of two Escherichia coli tRNA(Ser) acceptor stem microhelices. As both tRNAs are aminoacylated by the same seryl-tRNA-synthetase, we performed a comparative structure analysis of both duplexes to investigate the helical conformation, the hydration patterns and magnesium binding sites. It is well accepted, that the hydration of RNA plays an important role in RNA-protein interactions and that the extensive solvent content of the minor groove has a special function in RNA. The detailed comparison of both tRNA(Ser) microhelices provides insights into the structural arrangement of the isoacceptor tRNA aminoacyl stems with respect to the surrounding water molecules and may eventually help us to understand their biological function at atomic resolution. PMID- 20361935 TI - Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes. AB - Heterozygous mutations in the TP63 transcription factor underlie the molecular basis of several similar autosomal dominant ectodermal dysplasia (ED) syndromes. Here we provide a novel cellular model derived from embryonic stem (ES) cells that recapitulates in vitro the main steps of embryonic skin development. We show that ES cells carrying AEC or EEC mutations are unable to differentiate into the epidermal fate. Comparative transcriptome analysis strongly reveals an embryonic epidermal signature and suggests that mutations in the SAM domain (AEC) provide activating properties while mutations in the DBD domain (EEC) induce strong inhibitory capabilities. Our model uncovers the effect of relevant ED mutations that otherwise are difficult to evaluate on the ectodermal embryonic stage, an embryonic event critical for proper skin formation. PMID- 20361936 TI - Cytosolic pro-apoptotic SPIKE induces mitochondrial apoptosis in cancer. AB - Proteins of the BCL-2 family are important regulators of apoptosis. The BCL-2 family includes three main subgroups: the anti-apoptotic group, such as BCL-2, BCL-XL, BCL-W, and MCL-1; multi-domain pro-apoptotic BAX, BAK; and pro-apoptotic "BH3-only" BIK, PUMA, NOXA, BID, BAD, and SPIKE. SPIKE, a rare pro-apoptotic protein, is highly conserved throughout the evolution, including Caenorhabditis elegans, whose expression is downregulated in certain tumors, including kidney, lung, and breast. In the literature, SPIKE was proposed to interact with BAP31 and prevent BCL-XL from binding to BAP31. Here, we utilized the Position Weight Matrix method to identify SPIKE to be a BH3-only pro-apoptotic protein mainly localized in the cytosol of all cancer cell lines tested. Overexpression of SPIKE weakly induced apoptosis in comparison to the known BH3-only pro-apoptotic protein BIK. SPIKE promoted mitochondrial cytochrome c release, the activation of caspase 3, and the caspase cleavage of caspase's downstream substrates BAP31 and p130CAS. Although the informatics analysis of SPIKE implicates this protein as a member of the BH3-only BCL-2 subfamily, its role in apoptosis remains to be elucidated. PMID- 20361937 TI - GPR35 is a novel lysophosphatidic acid receptor. AB - GPR35 is a rhodopsin-like G protein-coupled receptor identified in 1998. It has been reported that kynurenic acid, a tryptophan metabolite, may act as an endogenous ligand for GPR35. However, the concentrations of kynurenic acid required to elicit the cellular responses are usually high, raising the possibility that another endogenous ligand may exist. In this study, we searched for another endogenous ligand for GPR35. Finally, we found that the magnitude of the Ca(2+) response induced by 2-acyl lysophosphatidic acid in the GPR35 expressing HEK293 cells was markedly greater than that in the vector-transfected control cells. Such a difference was not apparent in the case of 1-acyl lysophosphatidic acid. 2-Acyl lysophosphatidic acid also caused the sustained activation of RhoA and the phosphorylation of extracellular signal-regulated kinase, and triggered the internalization of the GPR35 molecule. These results strongly suggest that 2-acyl lysophosphatidic acid is an endogenous ligand for GPR35. PMID- 20361938 TI - The cargo receptor p24A facilitates calcium sensing receptor maturation and stabilization in the early secretory pathway. AB - The calcium sensing receptor (CaSR) is a Family 3/C G protein-coupled receptor with slow and partial targeting to the plasma membrane in both native and heterologous cells. We identified cargo receptor family member p24A in yeast two hybrid screens with the CaSR carboxyl terminus. Interactions were confirmed by immunoprecipitation of either p24A or CaSR in transiently transfected HEK293 cells. Only the immaturely glycosylated form of CaSR interacts with p24A. Dissociation likely occurs in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) or cis-Golgi, since only the uncleaved form of a CaSR mutant sensitive to the trans-Golgi enzyme furin was co-immunoprecipitated with p24A. p24A and p24A(DeltaGOLD) significantly increased total and plasma membrane CaSR protein but p24A(FF/AA) did not. The CaSR carboxyl terminus distal to T868 is required for differential sensitivity to p24A and its mutants. Interaction with p24A therefore increases CaSR stability in the ER and enhances plasma membrane targeting. Neither wt Sar1p or the T39N mutant increased CaSR maturation or abundance while the H79G mutant increased abundance but prevented maturation of CaSR. These results suggest that p24A is the limiting factor in CaSR trafficking in the early secretory pathway, and that cycling between the ER and ERGIC protects CaSR from degradation. PMID- 20361939 TI - The non-structural (NS1) protein of influenza A virus associates with p53 and inhibits p53-mediated transcriptional activity and apoptosis. AB - NS1 protein of influenza A virus is involved in regulating the apoptosis of infected cells. We found that exogenously expressed NS1 was able to associate with the tumor suppressor p53 that plays an essential role in regulating apoptosis of influenza A virus-infected cells. Exogenous expression of NS1 resulted in inhibition of p53-mediated transcriptional activity and apoptosis. The p53 inhibitory domain of NS1 was located between amino acids 144 and 188. This domain is necessary for NS1 to inhibit p53 activity, but it requires additional region(s) to cooperatively exert this inhibitory function. PMID- 20361940 TI - Regulation of survivin by PI3K/Akt/p70S6K1 pathway. AB - PI3K activation is commonly observed in many human cancer cells. Survivin expression is elevated in cancer cells, and induced by some growth factors through PI3K activation. However, it is not clear whether PI3K activation is sufficient to induce survivin expression. To investigate the role of PI3K pathway in the regulation of survivin, we expressed an active form of PI3K, v-P3k in chicken embryonic fibroblast cells (CEF), and found that overexpression of PI3K induced survivin mRNA expression. Forced expression of wild-type but not mutant tumor suppressor PTEN in CEF decreased survivin mRNA levels. PI3K regulates survivin expression through Akt activation. To further investigate downstream target of PI3K and Akt in regulating the expression of survivin mRNA, we found that PI3K and Akt-induced p70S6K1 activation and that overexpression of p70S6K1 alone was sufficient to induce survivin expression. The treatment of CEF cells by rapamycin decreased the survivin mRNA expression. This result demonstrated that p70S6K1 is an important target downstream of PI3K and Akt in regulating suvivin mRNA expression. The knockdown of survivin mRNA expression by its specific siRNA induced apoptosis of cancer cells when the cells were treated with LY294002 or taxol. Taken together, these results demonstrated that PI3K/Akt/p70S6K1 pathway is essential for regulating survivin mRNA expression. PMID- 20361941 TI - Identification and functional analysis of genes which confer resistance to cisplatin in tumor cells. AB - The efficacy of cisplatin during cancer chemotherapy is often impaired by the emergence of cancer cells which become resistant to chemotherapeutic agents. While various mechanisms have been proposed to explain resistance to cisplatin, the genes involved in this process still remain unclear. By using DNA microarrays, we performed a genome-wide analysis of cisplatin-resistant HeLa cells in order to identify genes involved in resistance. We identified nine genes (NAPA, CITED2, CABIN1, ADM, HIST1H1A, EHD1, MARK2, PTPN21, and MVD), which were consistently upregulated in two cisplatin-resistant HeLa cell lines. The upregulated genes, here referred to as cisplatin resistance genes (CPR), were further analyzed for their ability to modify the response of HEK293 cells to cisplatin. Short-hairpin RNA (shRNA) knockdown of CPR genes, individually or in combination, was shown to sensitize HEK293 cells to cisplatin, but not to vincristine or taxol, suggesting that CPR genes may be involved specifically in cisplatin resistance. Among the treatments performed, shRNA knockdown of NAPA was the most efficient treatment able to sensitize cells to cisplatin. Furthermore, shRNA knockdown of a single CPR gene was sufficient to partially reverse acquired cisplatin resistance in HeLa cells. Sensitization to cisplatin following knockdown of CPR genes was also observed in the tumorigenic cell lines Sk-ov-3, H1155, and CG-1. Based on these results, we propose that the CPR genes identified here may represent potential candidates for novel target therapies aimed at preventing resistance to cisplatin during chemotherapy. PMID- 20361942 TI - Characterisation of the heterotrimeric presynaptic phospholipase A(2) neurotoxin complex from the venom of the common death adder (Acanthophis antarcticus). AB - While Australo-Papuan death adder neurotoxicity is generally considered to be due to the actions of reversible competitive postsynaptic alpha-neurotoxins, the neurotoxic effects are often poorly reversed by antivenom or anticholinesterases. This suggests that the venom may contain a snake presynaptic phospholipase A(2) (PLA(2)) neurotoxin (SPAN) that binds irreversibly to motor nerve terminals to inhibit neurotransmitter release. Using size-exclusion liquid chromatography under non-reducing conditions, we report the isolation and characterisation of a high molecular mass SPAN complex, P-elapitoxin-Aa1a (P-EPTX-Aa1a), from the venom of the common death adder Acanthophis antarcticus. Using the chick biventer cervicis nerve-muscle preparation, P-EPTX-Aa1a (44,698Da) caused inhibition of nerve-evoked twitch contractions while responses to cholinergic agonists and KCl remained unaffected. P-EPTX-Aa1a also produced significant fade in tetanic contractions and a triphasic timecourse of neuromuscular blockade. These actions are consistent with other SPANs that inhibit acetylcholine release. P-EPTX-Aa1a was found to be a heterotrimeric complex composed of alpha, beta and gamma subunits in a 1:1:1 stoichiometry with each subunit showing significant N terminal sequence homology to the subunits of taipoxin, a SPAN from Oxyuranus s. scutellatus. Like taipoxin, only the alpha-chain produced any signs of neurotoxicity or displayed significant PLA(2) enzymatic activity. Preincubation with monovalent death adder antivenom or suramin, or inhibition of PLA(2) activity by incubation with 4-bromophenacyl bromide, either prevented or significantly delayed the onset of toxicity by P-EPTX-Aa1a. However, antivenom failed to reverse neurotoxicity. Early intervention with antivenom may therefore be important in severe cases of envenomation by A. antarcticus, given the presence of potent irreversible presynaptic neurotoxins. PMID- 20361943 TI - Obaculactone suppresses Th1 effector cell function through down-regulation of T bet and prolongs skin graft survival in mice. AB - Allograft rejection is a predominantly Th1 immune response. In this study, we showed that obaculactone, a natural compound derived from citrus fruit, prolonged skin graft survival in mice when treated after but not before transplantation. Furthermore, obaculactone inhibited alloantigen-specific production of Th1 cytokine IFN-gamma as well as proinflammatory cytokine IL-2, TNFalpha and IL-6. In parallel, IL-10 production was markedly up-regulated. Obaculactone significantly enhanced the percentage of CD4(+)CD25(+)Foxp3(+) Treg cells in the CD4(+) splenocytes without any effect on their inhibitory function. In vitro and in vivo tests showed obaculactone down-regulated T-bet expression in Th1 effector cells. Taken together, the unique immunomodulatory properties might qualify obaculactone as a putative, therapeutic compound for the treatment of Th1-driven diseases, including transplant rejection. PMID- 20361945 TI - Notch signaling: emerging molecular targets for cancer therapy. AB - The Notch signaling pathway is a highly conserved developmental pathway, which plays a critical role in cell-fate decision, tissue patterning and morphogenesis. There is increasing evidence that this pathway is dysregulated in a variety of malignancies, and can behave as either an oncogene or a tumor suppressor depending upon cell context. This review highlights the current evidence for aberration of the Notch signaling pathway in a wide range of tumors from hematological cancers, such as leukemia and lymphoma through to skin, breast, lung, pancreas, colon and brain tumors. It proposes that the Notch signaling pathway may represent novel therapeutic targets and will be a welcome asset to the cancer therapeutic arena. PMID- 20361946 TI - Upregulation of erythropoietin in rat peripheral nervous system with experimental autoimmune neuritis. AB - The glycoprotein erythropoietin (EPO) is a multifunctional cytokine involved in erythropoiesis. Recent data have suggested that EPO and EPO receptors are expressed in the central nervous system, where EPO exerts neuroprotective effects. However, peripheral nervous system (PNS) EPO and EPO receptor expression has not been widely studied. EPO and EPO receptor expression was examined in the PNS in an experimental autoimmune neuritis (EAN) rat model in the present study to elucidate EPO/EPO-receptor binding pathway involvement in injured PNS tissue. Western blot analysis demonstrated that EPO was significantly increased in the PNS at the paralytic stage on day 14 post-immunization (PI); levels were significantly decreased at day 30 PI. EPO was identified in PNS-derived vascular endothelial cells, Schwann cells, and axons in normal control rats. Most inflammatory cells in EAN lesions were EPO immunopositive at day 14 PI. In addition, the intensity of EPO immunoreactivity in both Schwann and vascular endothelial cells was greater than that of normal controls at this stage; intensity declined at day 30 PI. These findings suggest that EPO is transiently upregulated in EAN lesions and that the EPO/EPO-receptor binding pathway is associated with neuroprotection in EAN-affected PNS tissues. PMID- 20361944 TI - Methods for investigation of targeted kinase inhibitor therapy using chemical proteomics and phosphorylation profiling. AB - Phosphorylation acts as a molecular switch for many regulatory events in signaling pathways that drive cell division, proliferation, and apoptosis. Because of the critical nature of these protein post-translational modifications in cancer, drug development programs often focus on inhibitors for kinases and phosphatases, which control protein phosphorylation. Numerous kinase inhibitors have entered clinical use, but prediction of their efficacy and a molecular basis for patient response remain uncertain. Chemical proteomics, the combination of drug affinity chromatography with mass spectrometry, identifies potential target proteins that bind to the drugs. Phosphorylation profiling can complement chemical proteomics by cataloging modifications in the target kinases and their downstream substrates using phosphopeptide enrichment and quantitative mass spectrometry. These experiments shed light on the mechanism of disease development and illuminate candidate biomarkers to guide personalized therapeutic strategies. In this review, commonly applied technologies and workflows are discussed to illustrate the role of proteomics in examining tumor biology and therapeutic intervention using kinase inhibitors. PMID- 20361947 TI - Heme synthesis increases artemisinin-induced radical formation and cytotoxicity that can be suppressed by superoxide scavengers. AB - Artemisinin (ART) is a sesquiterpene lactone natural product that is widely used to treat multi-drug resistant strains of malaria. Artemisinin and its derivatives are also selectively cytotoxic to cancer cells, which can be modulated by altering heme synthesis. Cytotoxicity to cancer cells is thought to involve generation of oxidative stress, although conflicting data exist. We have analyzed reactive oxygen species (ROS) generation using the fluorescent probes 2',7' dichlorodihydrofluorescein diacetate (DCF) and dihydroethidine (HET) upon exposure to dihydroartemisinin (DHA) in Molt-4 leukemia cells. HET fluorescence correlated with dose-dependent DHA-induced cytotoxicity, increased within 30 min of DHA exposure, and was significantly enhanced by increasing heme synthesis. Protein levels of copper, zinc-superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase, and glutathione peroxidases 1/2 were also found to increase with DHA exposure. 4-hydroxy-tempol (TEMPOL) and DF-Mn, MnSOD mimetics, could significantly inhibit ROS generation and reduce cell death. Production of superoxide appears to be a central mediator of cytotoxicity from DHA. PMID- 20361948 TI - Adaptation of rat gastric tissue against indomethacin toxicity. AB - Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/ 3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX 2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism. PMID- 20361949 TI - Applications of neutron and X-ray scattering to the study of biologically relevant model membranes. AB - Scattering techniques, in particular electron, neutron and X-ray scattering have played a major role in elucidating the static and dynamic structure of biologically relevant membranes. Importantly, neutron and X-ray scattering have evolved to address new sample preparations that better mimic biological membranes. In this review, we will report on some of the latest model membrane results, and the neutron and X-ray techniques that were used to obtain them. PMID- 20361950 TI - Dipeptidyl peptidase-IV in synovial fluid and in synovial fluid mononuclear cells of patients with rheumatoid arthritis. AB - BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) enzymatic activity controls biological halftime of multiple local mediators. Its deregulation is associated with pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Although DPP-IV is the canonical representative of the group, a number of other proteins have been shown to have similar enzymatic activity. This study was aimed to identify the molecular source of DPP-IV activity in synovial fluid (SF) and fluid mononuclear cells (FMNC) in patients with RA and osteoarthritis (OA). In addition, the association of DPP-IV and the concentration of stromal cell derived factor-1alpha (SDF), DPP-IV substrate, were evaluated. METHODS: DPP-IV activity was measured by the kinetic fluorimetric method. The expression of studied molecules in FMNC and their concentrations in SF were assayed using flow cytometry and ELISA respectively. RESULTS: DPP-IV activity in SF, dominantly derived from the canonical DPP-IV, does not significantly differ between RA and OA. However, a significantly lower DPP-IV activity and expression in FMNC was found in RA as opposed to OA patients. Negative correlation between SDF concentration in SF and the relative amount of CD3+CD26+ cells was observed. CONCLUSIONS: We report decreased presence of DPP-IV/CD26 in CD3+ FMNC in RA, which also may participate on impaired balance of SDF concentration in SF. PMID- 20361951 TI - Effects of pretreatment protocols on human amniotic fluid protein profiling with SELDI-TOF MS using protein chips and magnetic beads. AB - BACKGROUND: There is increasing interest in the use of human amniotic fluid (AF) proteomics with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) for diagnosing pregnancy-associated abnormalities. A critical parameter of diagnostic biomarkers is the accuracy and reproducibility of protein patterns. We evaluated the effects of common pretreatment protocols on protein patterns generated using SELDI mass spectrometry with two different protein capture strategies (including functional protein chips and functionalized magnetic beads prior to MS analysis) in AF. METHOD: Various extrinsic factors involved in processing and storing amniotic fluid, including matrix composition, sample storage time, temperature and freeze-thaw cycles, were analyzed regarding their impact on AF protein patterns using SELDI mass spectrometry with 2 different protein capture strategies. RESULTS: Three extrinsic factors (sample storage for 3days at either room temperature or 4 degrees C or freeze-thawing the sample 5 times) significantly decreased the number or intensities of protein peaks detected in AF. Matrix dilutions also changed the spectra of AF, with more peaks and higher intensities observed with 50% alpha-cyano-4-hydroxycinnamic acid (CHCA). Moreover, protein chips captured more proteins or peptides than magnetic beads on SELDI-TOF MS profiling of AF. CONCLUSIONS: These results suggest that extrinsic factors must be taken into account for valid data interpretation to ensure good reproducibility of AF profiling by SELDI mass spectrometry. PMID- 20361952 TI - Effect of body mass index and total blood volume on serum cotinine levels among cigarette smokers: NHANES 1999-2008. AB - INTRODUCTION: Body mass index (BMI) and total blood volume are not always considered as variables that affect serum cotinine concentrations. METHOD: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2008 and fitted regression models for smokers. In addition to traditionally used covariates like age, race, gender, and average number of cigarettes smoked daily, we used BMI and total blood volume (TBV) as continuous variables to evaluate the impact of these variables on serum cotinine levels. RESULTS: Adjusted serum cotinine levels increased statistically significantly with increase in age (p<0.001). Serum cotinine levels increased statistically significantly (p<0.001) with average number of cigarettes smoked daily. Levels of adjusted serum concentrations from high to low by race/ethnicity were: non Hispanic blacks, non-Hispanic whites, other race/ethnicity, and Mexican Americans; and all differences were statistically significant. A model of serum cotinine including BMI without TBV found BMI to be a significant predictor (p<0.001) and similarly a model including TBV without BMI found TBV to be a significant predictor (p<0.001). When BMI and TBV were both included in the model, the significance of BMI changed markedly (p=0.93) with substantive changes in the BMI coefficient and the significance of TBV changed also (p=0.024) with small change in the TBV coefficient. DISCUSSION: TBV and BMI are significant predictors of serum cotinine concentrations. TBV or BMI, but not both, should be included in predictive models of serum cotinine concentrations. PMID- 20361953 TI - Comparison between the temperatures of intracellular ice formation in fresh mouse oocytes and embryos and those previously subjected to a vitrification procedure. AB - When cells that have been subjected to supposedly innocuous freezing or vitrification procedures are used as the source material for subsequent experiments, it is important that they possess or exhibit the same relevant properties as fresh cells. In this study, we compared the temperatures of intracellular ice formation (IIF) in previously vitrified mouse oocytes/embryos with those in fresh intact ones. In the case of MII oocytes, 2-cell embryos, 4-6 cell embryos, and morulae, there are no significant differences (p>0.05); namely, -33.3 degrees C (fresh) vs. -35.4 degrees C (vitrified) with MII oocytes, -40.6 degrees C (fresh) vs. -38.7 degrees C (vitrified) with 2-cell embryos, -38.0 degrees C (fresh) vs. -39.4 degrees C (vitrified) with 4-6-cell embryos, -24.5 degrees C (fresh) vs. -24.2 degrees C (vitrified) with morulae. But, in 8-cell embryos, there is a significant difference (p<0.05) between fresh (-37.9 degrees C) and vitrified (-32.9 degrees C). If we include this significant difference, the overall IIF temperature of fresh cells is 0.74 degrees C lower than that of previously vitrified cells. If we exclude it, the IIF temperature for fresh cells is 0.32 degrees C higher than that for previously vitrified cells. Our conclusion then is that there is no difference between the IIF temperatures of fresh and previously vitrified cells. PMID- 20361954 TI - Presence and vascular pharmacology of KATP channel subtypes in rat central and peripheral tissues. AB - K(ATP) channel openers are vasodilators and induce headache in normal subjects. We previously identified the Kir6.1/SUR2B K(ATP) channel subtype in major cerebral and dural arteries of rat, pig and man. We hypothesized that craniovascular Kir6.1/SUR2B K(ATP) channels mediate the headache-inducing effects of K(ATP) channel openers and that a Kir6.1/SUR2B specific blocker might be effective in the treatment of primary headaches such as migraine. Since K(ATP) channels are ubiquitous, we characterized the K(ATP) channel subtypes in major rat cranial and peripheral arteries and organs in order to understand the possible adverse effects of a Kir6.1/SUR2B blocker. We studied the mRNA expression of K(ATP) channel subunits in rat femoral, mesenteric, renal, coronary, basilar, middle cerebral and middle meningeal arteries and in tissue from rat heart, brain, liver, colon, lung, kidney and pancreas. We also studied the effects and potencies of a panel of synthetic K(ATP) channel openers and their potential inhibition by the Kir6.1 subunit-specific K(ATP) channel blocker PNU-37883A in segments of the arteries mounted in a wire myograph. Our studies suggest that Kir6.1/SUR2B forms the major functional K(ATP) channel complex in rat cranial and peripheral arteries. The mRNA transcripts of SUR1 and Kir6.2 subunits were predominantly found in brain, pancreas and heart, while SUR2A mRNA was merely detected within the heart. K(ATP) channel blockers highly specific for the SUR2B subunit may have no adverse CNS and cardiac effects and will not affect insulin release in the pancreas. However, a SUR2B blocker may not discriminate between cranial and peripheral arteries. PMID- 20361955 TI - Greater cytosolic and mitochondrial calcium transients in adrenal medullary slices of hypertensive, compared with normotensive rats. AB - Pronounced differences in the kinetics of single-vesicle catecholamine release from adrenal chromaffin cells stimulated with acetylcholine or high potassium (K(+)) have been recently found between normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Such differences could be explained on the basis of distinct mechanisms of calcium (Ca(2+)) handling by chromaffin cells of NWRs and SHRs. We have explored here this hypothesis in adrenal medullary slices loaded with calcium fluorescent probes to measure the changes in Ca(2+) concentration in the cytosol ([Ca(2+)](c)), endoplasmic reticulum ([Ca(2+)](er)), and mitochondria ([Ca(2+)](m)). We found the following differences on calcium handling in SHRs, as compared with NWR: (i) higher basal [Ca(2+)](c) and basal [Ca(2+)](m); (ii) greater [Ca(2+)](c) elevations elicited by acetylcholine and K(+), with faster activation but slower inactivation; (iii) greater [Ca(2+)](c) elevations elicited by CRT (a mixture of caffeine, ryanodine, and thapsigargin) and by the mitochondrial protonophore FCCP (carbonylcyanide p-(trifluoromethoxy) phenylhydrazone). The higher basal [Ca(2+)](c) and [Ca(2+)](m) suggest an enhanced mitochondrial Ca(2+) uptake, and the greater [Ca(2+)](c) elevations produced by FCCP indicates a higher mitochondrial Ca(2+) release into the cytosol. This alteration of intracellular Ca(2+) movements could explain the greater quantal catecholamine release responses seen in SHRs, as compared with NWRs in previous studies. Furthermore, enhanced mitochondrial Ca(2+) cycling may be the basis for the dysfunction of mitochondrial bioenergetics, reported to be present in hypertensive states. PMID- 20361956 TI - Spinal antinociception of synthetic omega-conotoxin SO-3, a selective N-type neuronal voltage-sensitive calcium channel blocker, and its effects on morphine analgesia in chemical stimulus tests in rodent. AB - SO-3, a novel Omega-superfamily conotoxin derived from Conus striatus, selectively inhibits N-type neuronal voltage-sensitive calcium channels. In current study, antinociception of SO-3 compared with MVIIA or morphine and its effects on morphine analgesia were investigated in rodent chemical stimulus tests after acute or repeated intrathecal administration. In mice acetic acid writhing test, similar to MVIIA, SO-3 caused dose- and time-dependent spinal antinociception with ED(50) of 0.25 microg/kg and t(1/2) of 4h, which was more potent and longer-acting than morphine. In rat formalin test after intrathecal bolus injection, SO-3 produced dose- and time-dependent antinociception by suppressing acute (ED(50), 1.79 microg/kg) and tonic phases (ED(50), 0.41 microg/kg), which was similar to MVIIA and approximately 10-fold potency and twice longer-acting of morphine in blocking tonic phase responses. After repeated intrathecal injections twice daily for 5 consecutive days, SO-3 produced analgesia without loss of potency whereas morphine produced analgesia tolerance in rat formalin test; further, SO-3 still produced potent analgesia in morphine tolerant rats. SO-3 co-administered with morphine left-shift the dose-response curve of morphine in mice acetic acid writhing test and significantly potentiated morphine analgesia in rat formalin test. No changes in motor function were seen in mice or rats receiving antinociceptive doses of SO-3 whereas MVIIA caused motor dysfunction at doses of 1.0-2.0 microg/kg in rats. This study showed that (1) novel SO-3 produced potent and long-acting spinal antinociception without observable motor dysfunction, (2) SO-3 significantly potentiated morphine analgesia, (3) After repeated intrathecal administration, SO-3 produced neither tolerance nor cross-tolerance to morphine analgesia. PMID- 20361957 TI - Phytoestrogen bavachin mediates anti-inflammation targeting Ikappa B kinase-I kappaB alpha-NF-kappaB signaling pathway in chondrocytes in vitro. AB - The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) plays critical roles in pathogenesis of osteoarthritis. Although estrogen is protective for cartilage in osteoarthritis patients, it also potentially increases the risk of stroke and cancer. Phytoestrogens acting as natural estrogen receptor modulators may serve as alternatives. This study aimed to identify medicinal phytoestrogens that preserve anti-inflammatory property and may function as potential chondro protective compounds. Both human chondrocytes and chondrocytic cell line CHON-002 were used for this study. Protein concentrations or expressions were measured by ELISA or Western blot, respectively. The DNA-binding activity and transcriptional activity of transcription factors were evaluated by electrophoretic mobility shift assay and dual-luciferase reporter assay, respectively. Cell migration was analyzed by chemotaxis assays. We found that among screened phytoestrogens, bavachin could potently decrease IL-1 beta-induced nuclear factor-kappa B (NF kappaB) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited I kappaB alpha degradation, increased nuclear translocation of p65 and p50 as well as decreased I kappaB alpha kinase (IKK) activity. Furthermore, bavachin inhibited IL-1 beta-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1 beta-induced activation of IKK-I kappaB alpha-NF-kappaB signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients. PMID- 20361958 TI - The quantitative evaluation of cholinergic markers in spatial memory improvement induced by nicotine-bucladesine combination in rats. AB - We previously showed that post-training intra-hippocampal infusion of nicotine bucladesine combination enhanced spatial memory retention in the Morris water maze. Here we investigated the role of cholinergic markers in nicotine bucladesine combination-induced memory improvement. We assessed the expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in CA1 region of the hippocampus and medial septal area (MSA) of the brain. Post training bilateral infusion of a low concentration of either nicotine or bucladesine into the CA1 region of the hippocampus did not affect spatial memory significantly. Quantitative immunostaining analysis of optical density in CA1 regions and evaluation of immunopositive neurons in medial septal area of brain sections from all combination groups revealed a significant increase (P<0.001) in the ChAT and VAChT immunoreactivity. The maximum increase was observed with combination of 10-microM/side bucladesine and 0.5 microg/side nicotine and in a concentration dependent manner. Also, increase in the optical density and amount of ChAT and VAChT immunostaining correlated with the decrease in escape latency and traveled distance in rats treated with nicotine and low dose of bucladesine. Taken together, these results suggest that significant increases of ChAT and VAChT protein expressions in the CA1 region and medial septal area are the possible mechanisms of spatial memory improvement induced by nicotine-bucladesine combination. PMID- 20361959 TI - Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. AB - Neuroinflammation is an important contributor to pathogenesis of neurological disorders, with microglial activation as a hallmark of neuroinflammation. Microglia serve the role of immune surveillance under normal conditions, but after brain damage or exposure to inflammation, microglia are activated and secrete pro-inflammatory and neurotoxic mediators. Sustained production of these factors contributes to neuronal damage. Therefore, inhibition of microglia mediated neuroinflammation may become a promising therapeutic target for neurological disorders. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, has beneficial health effects from its antioxidant, anticancer and anti-inflammatory properties. Recently, resveratrol has been shown to protect against various neurological disorders in experimental models, including brain ischemia, seizures, and neurodegenerative disease models. This minireview summarized the anti-inflammatory activities of resveratrol in the brain from both in vivo and in vitro studies, and highlighted the inhibition of activated microglia as a potential mechanism of neuroprotection. The release of various pro inflammatory factors, the production of reactive oxygen species, and the activation of signal pathways leading to neuroinflammation were discussed in relation to microglial activation. Taken together, microglia are an important target for anti-inflammatory activities of resveratrol in the brain. PMID- 20361960 TI - Cyclooxygenase-2 inhibitors prevent trinitrobenzene sulfonic acid-induced P glycoprotein up-regulation in vitro and in vivo. AB - Failed medical therapy is a common problem in inflammatory bowel disease. P glycoprotein (P-gp), an efflux pump encoded by MDR1 (ABCB1) gene can actively pump drugs out of cells conferring the phenotype of multidrug resistance. Various studies evoked that cyclooxygenase (COX) system may be involved in the regulation of P-gp activity. Since COX-2 isoform is overexpressed in colic inflammatory states, we examined the inhibitory effect of COX-2-inhibitors on P-gp expression and function under COX-2 stimulated conditions mediated by trinitrobenzene sulfonic acid (TNBS) in vitro, in Caco-2 cells, and in TNBS-induced colitis in mice. COX-2 and P-gp expressions were evaluated by real-time PCR and western blot. The activity of P-gp was measured by intracellular accumulation of rhodamine123 (Rho123) in Caco-2 cells and by Rho123 efflux using the intestinal everted loop method in mice. We showed that COX-2 stimulation in Caco-2 cells by 0.1mM TNBS exposure for 24h induced P-gp protein expression and activity. This activation was reversed by simultaneous COX-2-inhibitor treatment. Moreover, this effect was reproduced in vivo, in mice, where an increased P-gp expression and activity were observed 24h post intra-rectal TNBS administration. Induced P-gp expression and activity could be blocked by the oral pre-treatment with indomethacin heptyl ester (IHE) (20mg/kg). Administration of indomethacin heptyl ester had also a protective effect in TNBS-induced colitis. Our observations suggest that the inhibition of P-gp by COX-2-inhibitors could contribute to the improvement of medical response and this finding may have relevance to medical treatment of inflammatory bowel disease patients. PMID- 20361961 TI - Statin post-treatment provides protection against simulated ischemia in bovine pulmonary arterial endothelial cells. AB - Statins, inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, can have protective effects in various organs. We determined whether application of statins after a detrimental insult protected endothelial cells. Bovine pulmonary arterial endothelial cells (BPAEC) were subjected to a 5-h oxygen-glucose deprivation (OGD) and a 1-h simulated reperfusion. Simvastatin or atorvastatin alone or plus mevalonate (the immediate product of the reaction mediated by HMG-CoA reductase), geranylgeranyl pyrophosphate (GGPP, a product downstream of mevalonate), Ly294002 (a protein kinase B/Akt inhibitor), U0126 [an extracellular signal-regulated kinase (ERK) pathway inhibitor] or diphenyleneiodonium [a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor] were added to cells immediately after the OGD for 1h. Simvastatin and atorvastatin dose-dependently reduced the OGD and simulated reperfusion-induced lactate dehydrogenase (LDH) release from primary BPAEC and BPAEC between passage 4 and 15. This effect was inhibited by mevalonate, GGPP and Ly294002 and was not affected by U0126. Consistent with those results, simvastatin and atorvastatin increased the expression of phospho-Akt/activated Akt, and did not change the expression of phospho-ERK/activated ERK after the OGD and simulated reperfusion. The OGD and simulated reperfusion-induced LDH release and superoxide production, as measured by the dihydroethidium fluorescent intensity, were inhibited by diphenyleneiodonium. These results suggest that statin post-treatment reduces OGD and simulated reperfusion-induced cell injury. This effect may be mediated by inhibiting HMG-CoA reductase and the subsequent inhibition of small GTPases. GTPase activation depends on GGPP generation and contributes to the formation of NADPH oxidase complex that produces superoxide. The statin post-treatment-induced protection may also involve activated Akt. PMID- 20361962 TI - Characterization of vasoconstrictor-induced relaxation in the cerebral basilar artery. AB - The vascular endothelium regulates vascular smooth muscle functions by releasing endothelium-derived vasoactive substances. To identify physiological mechanisms mediating the inhibitory effect of the endothelium on vasoconstrictors, the basilar arteries isolated from Wistar rats were used in an organ bath study. In the intact basilar artery (with endothelium), 100 nM serotonin (5-HT) induced phasic contraction (28.7+/-4.1% of 60 mM KCl-induced contraction) followed by profound time-dependent relaxation at 3 min (3.8+/-0.4%). In the denuded artery (without endothelium), the 5-HT-induced contraction was enhanced (51.7+/-16.1%), while the relaxation was abolished. In the intact basilar artery, the contraction was facilitated and the amplitude of the phasic contraction was significantly enhanced (70.1+/-10.3%), but time-dependent relaxation was still manifested at 3 min (25.7+/-10.0%) in the presence of Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) and indomethacin. Time-dependent relaxation induced by 5 HT was abolished in Ca(2+)-free and in K(+)-free Krebs-Henseleit buffer (KHB). Furthermore, the 5-HT-induced contraction was enhanced by treatment with ouabain (105.6+/-11.8%), tetraethylammonium chloride (133.2+/-7.9%), charybdotoxin with apamin (145.4+/-6.4%) or BaCl(2) (72.2+/-13.8%) at 3 min; also, time-dependent relaxation was abolished by these blockers in the presence of L-NAME and indomethacin. U46619 (100 nM) induced sustained contraction without time dependent relaxation in normal KHB, but charybdotoxin with apamin did not affect the contraction. The results suggest that time-dependent relaxation is modulated by endothelial sodium-potassium pump (Na(+)/K(+)-ATPase) and Ca(2+)-activated K(+) channel (K(Ca)) activity, especially small- and intermediate-conductance K(Ca)-prominent ionic mechanisms of the so-called endothelium-derived hyperpolarizing factor. PMID- 20361963 TI - Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo. AB - In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo. PMID- 20361965 TI - Repeatable intra-individual variation in plasma testosterone concentration and its sex-specific link to aggression in a social lizard. AB - Individual hormone profiles can be important generators of phenotypic variation. Despite this, work on the consequences of hormone profiles has traditionally ignored the large inter-individual variation within natural populations. However, recent research has advocated the need to explicitly consider this variation and address its consequences for selection. One of the key steps in this process is examining repeatability in hormone profiles and their links to behavioral traits under selection. In this study we show that individuals within a free-ranging population of the Australian lizard Egernia whitii exhibit temporal repeatability in their circulating baseline testosterone concentrations as well as their aggressive response towards conspecific intruders. Furthermore, we show significant, sex-specific links between testosterone and aggression. Specifically, testosterone and aggression is negatively linked in males, while there is no relationship in females. As conspecific aggression has significant consequences for fitness-related traits (parental care, mating strategies) in this species, inter-individual variation in testosterone concentrations, through their effects on aggression, could have important implications for individual fitness. We discuss the potential causes and consequences of hormonal repeatability as well as provide explanations for its sex-specific links with aggression. Specifically, we suggest that these patterns are the result of alternative hormonal pathways governing aggression within Egernia and may indicate a decoupling of aggression and testosterone across the sexes. PMID- 20361964 TI - The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice. AB - Quercetin, a member of the flavonoid family, is one of the most prominent dietary antioxidants. This study investigates the mechanisms for the effects of quercetin on cultured human RPE cells and in Ccl2/Cx3cr1 double knock-out (DKO) mice, which spontaneously develop progressive retinal lesions mimicking age-related macular degeneration (AMD). In the in vitro experiment, cultured ARPE-19 cells were exposed to 1 mM H(2)O(2) with or without 50 muM quercetin for 2 h. Cellular viability, mitochondrial function, and apoptosis were assessed using crystal violet staining, MTT assay, and comet assay, respectively. Apoptotic molecular transcripts of BCL-2, BAX, FADD, CASPASE-3 and CASPASE-9 were measured by RQ-PCR. COX activity and nitric oxide (NO) level were determined in the supernatant of the culture medium. Quercetin treatment protected ARPE-19 cells from H(2)O(2) induced oxidative injury, enhanced BCL-2 transcript levels, increased the BCL 2/BAX ratio, suppressed the transcription of pro-apoptotic factors such as BAX, FADD, CASPASE-3 and CASPASE-9, inhibited the transcription of inflammatory factors such as TNF-alpha, COX-2 and INOS, and decreased the levels of COX and NO in the culture medium. In the in vivo experiment, DKO and C57/B6 mice were treated with 25 mg/kg/day quercetin by intraperitoneal injection daily for two months. Funduscopy was performed monthly. After two months, serum was collected to measure NADP(+)/NADPH, COX, PGE-2, and NO levels. The eyes were harvested for histology and A2E measurement. Ocular transcripts of Bcl-2, Bax, Cox-2, Inos, Tnf alpha, Fas, FasL and Caspase-3 were detected by RQ-PCR. Quercetin treatment did not reverse the progression of retinal lesions in DKO mice funduscopically or histologically. Although quercetin treatment could recover systemic anti oxidative capacity, suppress the systemic expression of NO, COX and PGE-2, and decrease ocular A2E levels, it could not effectively suppress the transcripts of the ocular inflammatory factors Tnf-alpha, Cox-2 and Inos, or the pro-apoptotic factors Fas, FasL and Caspase-3 in DKO mice. Our data demonstrate that quercetin can protect human RPE cells from oxidative stress in vitro via inhibition of pro inflammatory molecules and direct inhibition of the intrinsic apoptosis pathway. However, quercetin (25 mg/kg/day) does not improve the retinal AMD-like lesions in the Ccl2(-/-)/Cx3cr1(-/-) mice, likely due to its insufficient suppression of the inflammatory and apoptosis pathways in the eye. PMID- 20361966 TI - Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling. AB - In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-conditioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c(+) DCs as antigen-presenting cells and naive CD4(+) DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated maturation and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell proliferation, while preserving IL-10 production. DCs pulsed with TcES+OVA suppressed IFN-gamma, whereas they induced greater IL-4 production by CD4(+) DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation. PMID- 20361968 TI - Development and optimization of a cell-based neutralizing antibody assay using a sample pre-treatment step to eliminate serum interference. AB - We developed a neutralizing antibody assay (NAb assay), based upon the complement dependent cytotoxicity (CDC) activity of a monoclonal human IgG(1) therapeutic (IgT), to characterize anti-therapeutic antibodies (ATA) in autoimmune patient serum. Neutralizing antibodies (NAb) were measured by a decrease in the extent of CDC mediated by 50 ng/mL IgT, on a lymphoblastoid cell line. A sample pre treatment procedure, utilizing a Protein A/G resin to purify total immunoglobulins, was optimized for use in the NAb assay to eliminate the non specific assay interferents observed in individual serum samples from rheumatoid arthritis patients. In some individuals, the addition of naive serum to the assay completely inhibited CDC activity. After sample pre-treatment, the variability of the CDC response induced by IgT in individual serum samples from a drug-naive RA population, tested over three days, was only 3%, irrespective of complement immune complexes or rheumatoid factor levels. The pre-treatment procedure was performed on samples and matrix controls as part of each assay. The NAb assay was able to recover and detect polyclonal ATA from human serum at a concentration of 0.25 microg/mL with pre-treatment. Dose-dependent neutralization of IgT was observed, however, a simple positive/negative reporting scheme was adopted. The NAb assay was found to have the desired properties of specificity, robustness, precision and recovery for validation to support the characterization of ATA in clinical samples. PMID- 20361967 TI - The identification of a new Giardia duodenalis assemblage in marine vertebrates and a preliminary analysis of G. duodenalis population biology in marine systems. AB - Giardia duodenalis is an intestinal parasite of many vertebrates. The presence of G. duodenalis in the marine environment due to anthropogenic and wildlife activity is well documented, including the contributions from untreated sewage and storm water, agricultural run-off and droppings from terrestrial animals. Recently, studies have detected this protistan parasite in the faeces of marine vertebrates such as whales, dolphins, seals and shore birds. To explore the population biology of G. duodenalis in marine life, we determined the prevalence of G. duodenalis in two species of seal (Halichoerus grypus, Phoca vitulina vitulina and Phoca vitulina richardsi) from the east and west coasts of the USA, sequenced two loci from G. duodenalis-positive samples to assess molecular diversity and examined G. duodenalis distribution amongst these seals and other marine vertebrates along the east coast. We found a significant difference in the presence of G. duodenalis between east and west coast seal species. Only the zoonotic lineages of G. duodenalis, Assemblages A and B and a novel lineage, which we designated as Assemblage H, were identified in marine vertebrates. Assemblages A and B are broadly distributed geographically and show a lack of host specificity. Only grey seal (Halichoerus grypus) samples and one gull sample (Larus argentatus) from a northern location of Cape Cod, Massachusetts, USA, showed the presence of Assemblage H haplotypes; only one other study of harbour seals from the Puget Sound region of Washington, USA previously recorded the presence of an Assemblage H haplotype. Assemblage H sequences form a monophyletic clade that appears as divergent from the other seven Assemblages of G. duodenalis as these assemblages are from each other. The discovery of a previously uncharacterised lineage of G. duodenalis suggests that this parasite has more genetic diversity and perhaps a larger host range than previously believed. PMID- 20361969 TI - Comparison of a limiting dilution assay and ELISpot for detection of memory B cells before and after immunisation with a protein-polysaccharide conjugate vaccine in children. AB - In the present study, the limiting dilution assay (LDA) and the ELISpot are compared in their ability to detect serogroup C meningococcal (MenC)-specific memory B-cells in peripheral blood of 12month old children, after 3-dose priming with serogroup C meningococcal conjugate vaccine (MenCV) in infancy. At 12 months of age, MenC-memory B-cells were detected by ELISpot in 61% of children and in 5% by LDA. In contrast, carrier-specific memory B-cells were measurable in 36% of children by LDA and 78% by ELISpot. One month after a booster dose of MenCV given at 12 months of age, MenC-specific memory B-cells were detected in 89% of children by ELISpot and 65% of children by LDA, while diphtheria toxoid-specific memory B-cells were detected in 88% of children by ELISpot and in 74% of children by LDA. Two statistical methods were applied to enumerate memory B-cells with the LDA assay; the Poisson method allowed determination of very low frequencies that could not be determined by the Reed and Muench method. These data are examples of alternative methods to assess long-term protection after protein-polysaccharide conjugate vaccines, through direct measurement of memory B-cells in peripheral blood shortly after immunisation. PMID- 20361970 TI - Nitric oxide as a regulator of neuronal motility and regeneration in the locust embryo. AB - Nitric oxide (NO) is known as a gaseous messenger in the nervous system. It plays a role in synaptic plasticity, but also in development and regeneration of nervous systems. We have studied the function of NO and its signaling cascade via cyclic GMP in the locust embryo. Its developing nervous system is well suited for pharmacological manipulations in tissue culture. The components of this signaling pathway are localized by histochemical and immunofluorescence techniques. We have analyzed cellular mechanisms of NO action in three examples: 1. in the peripheral nervous system during antennal pioneer axon outgrowth, 2. in the enteric nervous system during migration of neurons forming the midgut nerve plexus, and 3. in the central nervous system during axonal regeneration of serotonergic neurons after axotomy. In each case, internally released NO or NO-induced cGMP synthesis act as permissive signals for the developmental process. Carbon monoxide (CO), as a second gaseous messenger, modulates enteric neuron migration antagonistic to NO. PMID- 20361971 TI - Coma in response to environmental stress in the locust: a model for cortical spreading depression. AB - Spreading depression (SD) is an interesting and important phenomenon due to its role in mammalian pathologies such as migraine, seizures, and stroke. Until recently investigations of the mechanisms involved in SD have mostly utilized mammalian cortical tissue, however we have discovered that SD-like events occur in the CNS of an invertebrate model, Locusta migratoria. Locusts enter comas in response to stress during which neural and muscular systems shut down until the stress is removed, and this is believed to be an adaptive strategy to survive extreme environmental conditions. During stress-induced comas SD-like events occur in the locust metathoracic ganglion (MTG) that closely resemble cortical SD (CSD) in many respects, including mechanism of induction, extracellular potassium ion changes, and propagation in areas equivalent to mammalian grey matter. In this review we describe the generation of comas and the associated SD-like events in the locust, provide a description of the similarities to CSD, and show how they can be manipulated both by stress preconditioning and pharmacologically. We also suggest that locust SD-like events are adaptive by conserving energy and preventing cellular damage, and we provide a model for the mechanism of SD onset and recovery in the locust nervous system. PMID- 20361972 TI - Circadian control of permethrin-resistance in the mosquito Aedes aegypti. AB - Daily fluctuation of permethrin-resistance was found in adult mosquito Aedes aegypti, the major vector of dengue viruses in Taiwan. We hypothesized there is a relationship between resistance and the circadian clock. To test our hypothesis we correlated changes in the knock-down time (KT(50)) response to permethrin with the expression of the pyrethroid-resistant gene CYP9M9 and the clock gene period (per) during a 12:12h photoperiodic cycle. Rhythmic expression of per peaked at early scotophase of the light-dark cycle and at early subjective night in constant darkness. The values of KT(50) and the expression of CYP9M9 also exhibited circadian rhythms in both susceptible and permethrin-resistant mosquito strains, from which we inferred a link to the circadian clock. The KT(50) was significantly longer in the light than in the dark phase, and the level of CYP9M9 mRNA was maximal in early scotophase, dropped to a minimum in the midnight and then slowly increased through the photophase. Existence of a clock control over mosquito sensitivity to permethrin was further indicated by reduced expression of CYP9M9 and reduced mosquito resistance to permethrin after temporal silencing of the per gene. These data provide the first evidence on the circadian control of insect resistance to permethrin. PMID- 20361973 TI - Phenol oxidases from Rhodnius prolixus: temporal and tissue expression pattern and regulation by ecdysone. AB - Rhodnius prolixus 5th instar nymphs have significant PO enzymatic activity in the anterior midgut, fat body and hemolymph. The tissue with the major amount of PO activity is the anterior midgut while those with higher specific activities are the fat body and hemolymph. In this work the temporal pattern of PO enzymatic activity in different tissues was investigated. In fat body, PO peaks occur at 7, 12 and 16 days after a blood meal. In hemolymph, PO diminishes until day 7, and then recovers by day 14. In the anterior midgut tissue, PO peaks on day 9 and just before ecdysis; a similar pattern was observed in the anterior midgut contents. Some of these activities are dependent on the release of ecdysone, as feeding blood meal containing azadirachtin suppresses them and ecdysone treatment counteracts this effect. These results suggest that during the development of the 5th instar, the insect has natural regulating cycles of basal PO expression and activation, which could be related to the occurrence of natural infections. The differences in temporal patterns of activity and the effects of azadirachtin and ecdysone in each organ suggest that, at least in R. prolixus, different tissues are expressing different PO genes. PMID- 20361974 TI - Developmental expression of mRNAs for epidermal and fat body proteins and hormonally regulated transcription factors in the tobacco hornworm, Manduca sexta. AB - This paper provides a compilation of diagrammatic representations of the expression profiles of epidermal and fat body mRNAs during the last two larval instars and metamorphosis of the tobacco hornworm, Manduca sexta. Included are those encoding insecticyanin, three larval cuticular proteins, dopa decarboxylase, moling, and the juvenile hormone-binding protein JP29 produced by the dorsal abdominal epidermis, and arylphorin and the methionine-rich storage proteins made by the fat body. The mRNA profiles of the ecdysteroid-regulated cascade of transcription factors in the epidermis during the larval molt and the onset of metamorphosis and in the pupal wing during the onset of adult development are also shown. These profiles are accompanied by a brief summary of the current knowledge about the regulation of these mRNAs by ecdysteroids and juvenile hormone based on experimental manipulations, both in vivo and in vitro. PMID- 20361975 TI - Ecdysteroid-mediated expression of hexamerin (arylphorin) in the rice moth, Corcyra cephalonica. AB - The insect development is intricately controlled by morphogenetic hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E) through the regulation of gene/protein expression. The role of hexamerins in the metamorphosis of insects and reproduction and their control by 20E at the gene level has been widely reported in insects. In the present study we for the first time report the role of ecdysteroids in the regulation of hexamerin synthesis in a lepidopteran insect Corcyra cephalonica. The hormonal studies were carried out using the normal and the thorax-ligated insects with both 20E and its non-steroidal agonist RH-5992. The in vitro as well as in vivo studies showed a stimulatory effect of 20E and its agonist on the hexamerin synthesis including arylphorin (Hex 2), whereas hormone blockade with azadirachtin caused a time dependent reduction in synthesis. The northern analysis using Hex 2b cDNA as probe too confirmed the above result. This was followed by the cloning of the Hex 2b gene. The full length of the genomic clone was found to be 3.5kb long and has four exons interspersed by three introns. The genome walking analysis revealed the presence of a steroid hormone binding sequence "Ecdysone response element" (EcRE) in the 5' untranscribed region (UTR) of the gene. The data presented in this paper clearly suggest that hexamerin synthesis in C. cephalonica is transcriptionally regulated by 20E. PMID- 20361976 TI - New microsporidia parasitizing bark lice (Insecta: Psocoptera). AB - Two species of bark lice, Xanthocaecilius sommermanae Mockford and Polypsocus corruptus Hagen, collected in a canopy Malaise trap placed in Great Smoky Mountains National Park as part of a survey of the park's fauna, were found to be infected with microsporidia. Diagnosis was originally based on light microscopy, and was confirmed by PCR amplification and electron microscopy. This is the first record of microsporidia infection in the insect order Psocoptera. Four morphological spore types corresponded to four original SSUrDNA sequences (Genbank accession no. FJ865221-24), suggesting infection with four microsporidia species. Two of those species were examined by electron microscopy. We describe here one new genus and two new species based on morphological and sequence data: Antonospora psocopterae sp. n. with elongated diplokaryotic spores, 4.4+/-0.05 x 1.9+/-0.03 microm and Mockfordia xanthocaeciliae gen. n. sp. n. with ovocylindrical monokaryotic spores, 2.5+/-0.10 x 1.4+/-0.02 microm. A. psocopterae displayed high sequence (95%) and structural similarity with Antonospora scoticae, fell within a well supported dichotomy with A. scoticae inside the Antonospora-Paranosema clade in phylogenetic analyses by NJ, PS and ML. M. xanthocaeciliae did not exhibit much sequence or structural similarity with any of known microsporidia species, except Encephalitozoon spp. M. xanthocaeciliae fell within one clade with Encephalitozoon spp. in phylogenies and shared with encephalitozoons structural resemblance and about 80% of SSUrDNA sequence identity. The other two species were not described and provisionally were placed to the collective genus Microsporidium as Microsporidium sp. 1 and Microsporidium sp. 4 from bark lice because of insufficient morphological data. The finding that samples fixed and stored for months in propylene glycol ("antifreeze") are good enough for DNA sequence analysis and can be used for morphological analyses (if no better fixation alternatives are available), is promising for future surveys for microsporidia. PMID- 20361977 TI - Single concentration tests show synergism among Bacillus thuringiensis subsp. israelensis toxins against the malaria vector mosquito Anopheles albimanus. AB - Bioassays of insecticidal proteins from Bacillus thuringiensis subsp. israelensis with larvae of the malaria vector mosquito Anopheles albimanus showed that the cytolytic protein Cyt1Aa was not toxic alone, but it increased the toxicity of the crystalline proteins Cry4Ba and Cry11Aa. Synergism also occurred between Cry4Ba and Cry11Aa toxins. Whereas many previous analyses of synergism have been based on a series of toxin concentrations leading to comparisons between expected and observed values for the concentration killing 50% of insects tested (LC(50)), we describe and apply a method here that enables testing for synergism based on single concentrations of toxins. PMID- 20361978 TI - Characterization of chitinolytic bacteria and histological aspects of Shell Disease Syndrome in European spiny lobsters (Palinurus elephas) (Fabricius 1787). AB - The present research reports the first description of Shell Disease Syndrome in European spiny lobsters Palinurus elephas (Fabricius 1787), which occurred in an experimental aquaculture facility in Sicily (Italy). Both bacterial characterization and histopathological examination of the exoskeleton at site of lesions was carried out. Infected specimens showed tail fan erosions, and in one case uropod ulceration and complete loss of periods. Identified species included: Listonella anguillarum 50.5%, Vibrio parahaemolyticus 27.5% and Vibrio alginolyticus 22%. Microscopic evaluation of lesions indicate the presence of inflammatory responses, which include melanization and pseudomembrane formation, similar to those described for other crustaceans affected by SDS. PMID- 20361979 TI - Solution structure and characterisation of the human pyruvate dehydrogenase complex core assembly. AB - Mammalian pyruvate dehydrogenase complex (PDC) is a key multi-enzyme assembly that is responsible for glucose homeostasis maintenance and conversion of pyruvate into acetyl-CoA. It comprises a central pentagonal dodecahedral core consisting of two subunit types (E2 and E3BP) to which peripheral enzymes (E1 and E3) bind tightly but non-covalently. Currently, there are two conflicting models of PDC (E2+E3BP) core organisation: the 'addition' model (60+12) and the 'substitution' model (48+12). Here we present the first ever low-resolution structures of human recombinant full-length PDC core (rE2/E3BP), truncated PDC core (tE2/E3BP) and native bovine heart PDC core (bE2/E3BP) obtained by small angle X-ray scattering and small-angle neutron scattering. These structures, corroborated by negative-stain and cryo electron microscopy data, clearly reveal open pentagonal core faces, favouring the 'substitution' model of core organisation. The native and recombinant core structures are all similar to the truncated bacterial E2 core crystal structure obtained previously. Cryo-electron microscopy reconstructions of rE2/E3BP and rE2/E3BP:E3 directly confirm that the core has open pentagonal faces, agree with scattering-derived models and show density extending outwards from their surfaces, which is much more structurally ordered in the presence of E3. Additionally, analytical ultracentrifugation characterisation of rE2/E3BP, rE2 (full-length recombinant E2-only) and tE2/E3BP supports the substitution model. Superimposition of the small-angle neutron scattering tE2/E3BP and truncated bacterial E2 crystal structures demonstrates conservation of the overall pentagonal dodecahedral morphology, despite evolutionary diversity. In addition, unfolding studies using circular dichroism and tryptophan fluorescence spectroscopy show that the rE2/E3BP is less stable than its rE2 counterpart, indicative of a role for E3BP in core destabilisation. The architectural complexity and lower stability of the E2/E3BP core may be of benefit to mammals, where sophisticated fine-tuning is required for cores with optimal catalytic and regulatory efficiencies. PMID- 20361980 TI - What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf. AB - Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. PMID- 20361981 TI - Inhibition of CtBP1 activity by Akt-mediated phosphorylation. AB - Pc2 (Cbx4) is a member of the chromobox family of polycomb proteins, and is a SUMO E3 ligase for the transcriptional corepressor CtBP1. Here, we show that both CtBP1 and Pc2 are phosphorylated by the kinase Akt1, which is activated by growth factor signaling via the PI3-kinase pathway. In the presence of Pc2, phosphorylation of CtBP1 is increased, and this requires interaction of both CtBP1 and Akt1 with Pc2. Pc2 promotes CtBP1 phosphorylation by recruiting Akt1 and, in part, by preventing de-phosphorylation of activated Akt1. Alteration of the Akt-phosphorylated residue in CtBP1 to a phosphomimetic results in decreased CtBP1 dimerization, but does not prevent interaction with other transcriptional regulators. The phosphomimetic mutant of CtBP1 is expressed at a lower level than the wild type protein, resulting in decreased transcriptional repression. We show that this CtBP1 mutant is targeted for poly-ubiquitylation and is less stable than the wild type protein. Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation. This work suggests that Pc2 might coordinate multiple enzymatic activities to regulate CtBP1 function. PMID- 20361983 TI - Putting phylogeny into the analysis of biological traits: a methodological approach. AB - Phylogenetic comparative methods have long considered phylogenetic signal as a source of statistical bias in the correlative analysis of biological traits. However, the main life-history strategies existing in a set of taxa are often combinations of life history traits that are inherently phylogenetically structured. In this paper, we present a method for identifying evolutionary strategies from large sets of biological traits, using phylogeny as a source of meaningful historical and ecological information. Our methodology extends a multivariate method developed for the analysis of spatial patterns, and relies on finding combinations of traits that are phylogenetically autocorrelated. Using extensive simulations, we show that our method efficiently uncovers phylogenetic structures with respect to various tree topologies, and remains powerful in cases where a large majority of traits are not phylogenetically structured. Our methodology is illustrated using empirical data, and implemented in the adephylo package for the free software R. PMID- 20361982 TI - The Tiam1 PDZ domain couples to Syndecan1 and promotes cell-matrix adhesion. AB - The T-cell lymphoma invasion and metastasis gene 1 (Tiam1) is a guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions. This GEF contains several protein-protein interaction domains, including a PDZ domain. Earlier studies identified a consensus PDZ-binding motif and a synthetic peptide capable of binding to the Tiam1 PDZ domain, but little is known about its ligand specificity and physiological role in cells. Here, we investigated the structure, specificity, and function of the Tiam1 PDZ domain. We determined the crystal structures of the Tiam1 PDZ domain free and in complex with a "model" peptide, which revealed the structural basis for ligand specificity. Protein database searches using the consensus PDZ-binding motif identified two eukaryotic cell adhesion proteins, Syndecan1 and Caspr4, as potential Tiam1 PDZ domain binding proteins. Equilibrium binding experiments confirmed that C-terminal peptides derived from Syndecan1 and Caspr4 bound the Tiam1 PDZ domain. NMR chemical shift perturbation experiments indicated that the Tiam1 PDZ/Syndecan1 and PDZ/Caspr4 complexes were structurally distinct and identified key residues likely to be responsible for ligand selectivity. Moreover, cell biological analysis established that Syndecan1 is a physiological binding partner of Tiam1 and that the PDZ domain has a function in cell-matrix adhesion and cell migration. Collectively, our data provide insight into the structure, specificity, and function of the Tiam1 PDZ domain. Importantly, our data report on a physiological role for the Tiam1 PDZ domain and establish a novel link between two previously unrelated signal transduction pathways, both of which are implicated in cancer. PMID- 20361984 TI - Decreased binding of [11C]NNC112 and [11C]SCH23390 in patients with chronic schizophrenia. AB - AIMS: Abnormality of cognitive function in schizophrenia has been suggested to be related to dopamine D1 receptor. However, the results of previous positron emission tomography (PET) studies of dopamine D1 receptor in schizophrenia were not consistent. MAIN METHODS: In this study, six patients with schizophrenia in severe residual phase with chronic antipsychotic treatment and twelve healthy age matched controls participated. Two different radioligands, [11C]NNC112 and [11C]SCH23390, for dopamine D1 receptor were used on the same subjects. Binding of the ligands was measured by PET, and statistical analysis was performed using one-way analysis of covariate (ANCOVA) with age as covariate. KEY FINDINGS: Good correlations between binding potential values (BP(ND)) and age were observed in all regions of interest (ROIs) with both ligands. ANCOVA with age as covariate of BP(ND) values of all ROIs revealed that the patient group showed significantly lower BP(ND) value compared with the control group in both ligands. SIGNIFICANCE: In patients with chronic schizophrenia in severe residual phase with chronic antipsychotic treatment, the binding potential values of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls. PMID- 20361985 TI - Timing of testing and treatment for asymptomatic diseases. AB - Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases. We provide a computationally efficient method for determining a cost-effective dynamic intervention strategy that takes into account (i) the results of the previous test for each individual and (ii) the change in the individual's behavior based on awareness of the disease. We demonstrate the usefulness of the approach by applying the results to screening decisions for Hepatitis C (HCV) using medical data, and compare our findings to current HCV screening recommendations. PMID- 20361987 TI - Noradrenaline acting at beta-adrenoceptors induces expression of IL-1beta and its negative regulators IL-1ra and IL-1RII, and drives an overall anti-inflammatory phenotype in rat cortex. AB - Evidence indicates that noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and plays a neuroprotective role where inflammatory events contribute to pathology. Here we examined the ability of pharmacological enhancement of central noradrenergic tone to impact upon activation of the IL-1 system in rat brain. Treatment with the noradrenaline reuptake inhibitor reboxetine combined with the alpha(2)-adrenoceptor antagonist idazoxan induced expression of IL-1beta as well as its negative regulators, IL-1 receptor antagonist (IL-1ra) and IL-1 type II receptor (IL-1RII) in rat cortex. The ability of reboxetine/idazoxan treatment to activate the IL-1 system was mediated by beta-adrenoceptors, as the aforementioned effects were blocked by the beta adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant beta(2)-adrenoceptor agonist clenbuterol induced expression of IL 1beta, IL-1ra and IL-1RII in rat brain. This action was selective to the IL-1 system, as other inflammatory cytokines including TNF-alpha, IL-6 or IFN-gamma were not induced by clenbuterol. Induction of IL-1beta was accompanied by activation of NFkappaB and of the MAP kinase ERK, and clenbuterol also induced expression of the IL-1beta-inducible gene CINC-1. The ability of clenbuterol to activate the IL-1 system was blocked by propranolol, and was mimicked by the highly selective beta(2)-adrenoceptor agonist formoterol. Despite the ability of clenbuterol to activate the central IL-1 system, it largely combated the neuroinflammatory response induced by systemic inflammatory stimulus (bacterial lipopolysaccharide; LPS). Specifically, whilst the ability of clenbuterol to induce expression of IL-1RII and IL-1Ra was maintained following the inflammatory challenge, its ability to induce IL-1beta was reduced. In addition, clenbuterol suppressed LPS-induced expression of the inflammatory cytokines TNF-alpha and IL 6, the inflammatory chemokines RANTES and IP-10, the co-stimulatory molecules CD40 and ICAM-1. Thus overall, clenbuterol suppresses the innate inflammatory response in rat brain. PMID- 20361986 TI - 5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease. AB - Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. PMID- 20361988 TI - Finding Wally: prism adaptation improves visual search in chronic neglect. AB - Several studies have found that visuo-motor adaptation to rightward deviating prismatic goggles (prism adaptation) can alleviate symptoms of neglect after brain damage, but the long-term effect and clinical relevance of this rehabilitation approach have been questioned. In particular, the effect on visual search performance is controversial. In the present study 6 patients with chronic spatial neglect due to rightsided focal brain damage were given 20 sessions of prism adaptation over a period of two weeks. These patients, as well as a matched control group of neglect patients (n=5), were tested using a variety of effect measures with special emphasis on visual search at baseline, shortly after training, and five weeks later. A positive and very consistent long-term effect of prism adaptation was found across clinical tests of neglect, lateral bias of eye movements, and measures of everyday function, including subjective reports. The results show that prism adaptation can provide durable and clinically significant alleviation of neglect symptoms, even in the stable phase of recovery. PMID- 20361989 TI - Neurobiology of hyperactivity and reward: agreeable restlessness in anorexia nervosa. AB - Restricted food intake is associated with increased physical activity, very likely an evolutionary advantage, initially both functional and rewarding. The hyperactivity of patients with anorexia nervosa, however, is a main problem for recovery. This seemingly paradoxical reward of hyperactivity in anorexia nervosa is one of the main aspects in our framework for the neurobiological changes that may underlie the development of the disorder. Here, we focus on the neurobiological basis of hyperactivity and reward in both animals and humans suggesting that the mesolimbic dopamine and hypothalamic orexin neurons play central roles. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. PMID- 20361990 TI - Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor. AB - Endosulfan is an organochlorine pesticide commonly used in agriculture. Endosulfan has affects on vertebrate xenobiotic metabolism pathways that may be mediated, in part, by its ability to activate the pregnane X receptor (PXR) and/or the constitutive androstane receptor (CAR) which can elevate expression of cytochrome P450 (CYP) enzymes. This study examined the dose-dependency and receptor specificity of CYP induction in vitro and in vivo. The HepG2 cell line was transiently transfected with CYP2B6- and CYP3A4-luciferase promoter reporter plasmids along with human PXR (hPXR) or hCAR expression vectors. In the presence of hPXR, endosulfan-alpha exposure caused significant induction of CYP2B6 (16 fold) and CYP3A4 (11-fold) promoter activities over control at 10 microM. The metabolite endosulfan sulfate also induced CYP2B6 (12-fold) and CYP3A4 (6-fold) promoter activities over control at 10 microM. In the presence of hCAR-3, endosulfan-alpha induced CYP2B6 (2-fold) promoter activity at 10 microM, but not at lower concentrations. These data indicate that endosulfan-alpha significantly activates hPXR strongly and hCAR weakly. Using western blot analysis of human hepatocytes, the lowest concentrations at which CYP2B6 and CYP3A4 protein levels were found to be significantly elevated by endosulfan-alpha were 1.0 microM and 10 microM, respectively. In mPXR-null/hPXR-transgenic mice, endosulfan-alpha exposure (2.5mg/kg/day) caused a significant reduction of tribromoethanol-induced sleep times by approximately 50%, whereas no significant change in sleep times was observed in PXR-null mice. These data support the role of endosulfan-alpha as a strong activator of PXR and inducer of CYP2B6 and CYP3A4, which may impact metabolism of CYP2B6 or CYP3A4 substrates. PMID- 20361991 TI - Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering. AB - Bone tissue engineering is an alternative strategy to generate bone utilizing a combination of biomaterials and cells. Biomaterials that mimic the structure and composition of bone tissues at nanoscale are important for the development of bone tissue engineering applications. Natural or biopolymer-based composites containing chitin, chitosan, or collagen have advantages such as biocompatibility, biodegradability that are essential for bone tissue engineering. The inclusion of nanoparticles of hydroxyapatite (one of the most widely used bioceramic materials) into the biopolymer matrix improves the mechanical properties and incorporates the nanotopographic features that mimic the nanostructure of bone. This review summarizes the recent work on the development of biocomposites containing natural polymers with hydroxyapatite particles suitable for use in bone defects/bone regeneration. PMID- 20361992 TI - Chemical structure and immunoinhibitory activity of a pectic polysaccharide containing glucuronic acid from the leaves of Diospyros kaki. AB - Pectin is a family of complex polysaccharides characterized by the presence of 1,4-linked alpha-galacturonic acid residues in the backbone and is more recognized for its potential bioactive properties. Herein we reported the structural and biological features of a pectic fraction DL-4OAC-1 from the leaves of Diospyros kaki. Chemical and spectral analysis revealed this polysaccharide possessed a backbone composed of a repeating disaccharide [-->4)-alpha-GalAp-(1- >2)-alpha-Rhap-(1-->], substituted at some O-4 of Rhap residues and O-3 of GalAp residues by the side chains consisting of Araf, Galp, Xylp, and in particular terminal GlcAp residues. The immunological assay in vitro showed that this distinct pectic fraction could inhibit the LPS-induced B lymphocyte proliferation and had no effect on the ConA-induced T lymphocyte proliferation. PMID- 20361993 TI - Wide-angle X-ray scattering as a probe for insulin denaturation. AB - Wide-angle X-ray scattering (WAXS) from lyophilized protein is characterized by the presence of two relatively broad scattering peaks that are linked to protein structure. This work is concerned with the possibility of utilizing these peaks in the probing of the unfolding and breakdown of insulin. Native insulin is subject to thermal denaturation in the presence and in the absence of thiol catalysts. Denatured products are acid-trapped, lyophilized and monitored using WAXS in addition to Fourier transform infrared spectroscopy (FTIR), gel filtration chromatography and Transmission Electron Microscopy (TEM) as supportive techniques. Results show that the WAXS peak at a d-spacing about 10 A is sensitive towards the alpha-helix content of insulin. A reduction in the intensity of such peak is proven to be directly linked to the reduction of native insulin having normal alpha-helix content. The supportive techniques confirmed the decrease in the alpha-helix content of insulin which accompanied the different denaturation treatments. PMID- 20361994 TI - Sorption of chromium(VI) using modified forms of chitosan beads. AB - Modified forms of chitosan beads were prepared and used for chromium removal from the aqueous solution. The prepared chitosan beads viz., protonated chitosan beads (PCB), carboxylated chitosan beads (CCB) and grafted chitosan beads (GCB) possess enhanced chromium sorption capacities (SCs) of 3239, 3647 and 4057 mg/kg respectively than the raw chitosan beads (CB) which possess the SC of 1298 mg/kg with a minimum contact time of 10min. The sorption experiments were carried out in batch mode to optimize various influencing parameters viz., contact time, pH, common ions and temperature. The sorbents were characterized by FTIR and SEM with EDAX analysis. The modified chitosan beads remove chromium by means of electrostatic adsorption coupled reduction and complexation. The adsorption data was fitted with Freundlich and Langmuir isotherms. The calculated values of thermodynamic parameters indicate the nature of chromium sorption. A field trial was carried out with water collected from a nearby industrial area. PMID- 20361995 TI - Plant proteins as binders in cellulosic paper composites. AB - Plant proteins are used - for the first time - in this work as bulk binders for cellulosic fibers in paper composites. Soy bean protein and wheat gluten were denatured by two methods, namely by: urea+NaOH and by urea+NaOH+acrylamide. Addition of increased amounts of the denatured proteins resulted in a significant increase in all paper strength properties. Soy protein led, in addition, to a remarkable enhancement in opacity. The use of proteins increased kaolin retention in the paper composites, while keeping the paper strength higher than the blank protein-free paper. The results show that plant proteins are favorable than synthetic adhesives; because they are biodegradable and do not cause troubles in paper recycling i.e. they are environmentally friendly. PMID- 20361996 TI - Gene-environment interactions in neurotoxicology: the 12th biennial meeting of the International Neurotoxicology Association. PMID- 20361997 TI - A review of mortality due to Clostridium difficile infection. AB - SUMMARY: In this review we examine published literature to ascertain mortality in relation to Clostridium difficile infection (CDI) and the factors associated with mortality. In the 27 studies that had sufficient data, there were 10975 cases of CDI with great heterogeneity in the methods for reporting mortality. We calculated the overall associated mortality to be at least 5.99% within 3 months of diagnosis. The most important finding is that higher mortality is associated with advanced age, being 13.5% in patients over 80 years. Studies performed after 2000 had a significantly higher mortality than those before this date. We propose minimum standards for reporting mortality in future studies. PMID- 20361998 TI - Fetal death as a result of placental immune reconstitution inflammatory syndrome. AB - A 26-year-old woman was HIV-1 diagnosed at 11 weeks of pregnancy (CD4 = 7/mm(3), HIV-1 RNA = 108,000 copies/mL) with immunity against toxoplasmosis (Toxoplasma IgG = 1800 UI/mL). A fetal death was diagnosed 7 weeks after starting HAART (CD4 = 185/mm(3), HIV-1 RNA = 391 copies/mL) with a positive Toxoplasma PCR on fetal tissues and amniotic fluid. The absence of severe toxoplasmic foetopathy, the very exaggerated and atypical placental inflammation and the immune restoration context led to the diagnosis of placental IRIS associated with Toxoplasma gondii reactivation. This outcome remains undescribed and could represent an issue in resource-limited settings where HIV-pregnant patients are often severely immunodeficient and infected with opportunistic pathogens. PMID- 20361999 TI - The in vitro evaluation of tigecycline tested against pathogens isolated in eight countries in the Asia-Western Pacific region (2008). AB - OBJECTIVES: To determine the in vitro activity of tigecycline and comparator common use antimicrobial agents tested against contemporary bacterial pathogens from the Asia-Western Pacific region. METHODS: As part of the SENTRY Antimicrobial Surveillance Program, a total of 5759 Gram-positive and Gram negative isolates were collected from 28 medical centers in eight Asia-Western Pacific countries during 2008. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution method and interpreted using CLSI breakpoints. United States Food and Drug Administration (US-FDA) breakpoints were used to interpret tigecycline susceptibility. RESULTS: Antimicrobial resistance was found to be widespread and prevalence varied considerably between the eight countries. Against pathogens for which breakpoints were available, >98% of all isolates were susceptible to tigecycline. Against all Gram-positive isolates, including methicillin (oxacillin)-resistant Staphylococcus aureus, penicillin- and multidrug-resistant pneumococci, and vancomycin-resistant enterococci, the highest tigecycline MIC found was 1 microg/ml. Against all Enterobacteriaceae, including extended spectrum beta-lactamase phenotypes, tigecycline susceptibility was 97.5%. Tigecycline had good activity against Acinetobacter spp. but was much less active against Pseudomonas aeruginosa. CONCLUSION: Tigecycline demonstrated excellent sustained in vitro activity against a wide spectrum of contemporary Gram-positive and -negative pathogens from Asia-Western Pacific countries. PMID- 20362000 TI - Brucella endocarditis, a report of 14 cases (1991-2009). PMID- 20362001 TI - Recognition of secretory IgA by DC-SIGN: implications for immune surveillance in the intestine. AB - Secretory IgA (SIgA), the predominant class of antibody in intestinal secretions, serves as the first line of defense against enteric infections. SIgA has also been proposed to function in immune surveillance, given that both SIgA and SIgA antigen complexes are actively transported by Peyer's patch M cells from the intestinal lumen to sub-epithelial dendritic cells (DCs). The goal of the present study was to identify the receptor(s) potentially utilized by mucosal DCs to recognize and internalize SIgA. We demonstrate that human colostral SIgA is recognized by purified recombinant human DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) in a solid phase binding assay, as well as by DC-SIGN ectopically expressed on the surface of Chinese hamster ovary (CHO-S) cells. The interaction between SIgA and DC-SIGN was specific, given that it was Ca(2+)-dependent and inhibited by mannan. Moreover, SIgA bound to, and was internalized by, endogenous DC-SIGN expressed on THP-1 cells following monocyte to macrophage-like cell differentiation by stimulation with phorbol ester and interleukin-4. These data identify DC-SIGN as a putative receptor for SIgA, and reveal a mechanism by which DCs could collaborate with M cells in immune surveillance at mucosal surfaces. PMID- 20362002 TI - Generation of random mutant libraries with multiple primers in a single reaction. AB - Characterization of multiple sites in a single gene that are important in biological phenotypes is challenging due to the difficulty to generate many mutants representing all or a majority of combinations of mutations in the gene. Using the HIV-1 env and pol genes as templates, four random libraries were generated representing different combinations of mutations introduced by up to 36 mutagenesis primers in a single assay. Over 86% of the clones contained mutations and the mutants tended to have single or fewer mutations in the libraries. When protein size was used as a screening marker, all identified clones contained at least 2 mutations and up to 12 mutations were detected in a single clone. Nearly all mutant clones in each library contained unique mutations, indicating that mutants in the library were generated at random. Closely related mutations which were overlapped by neighboring mutagenesis primers were often introduced in this system. Analysis of the env library showed that some potential N-linked glycosylation sites did not increase the Env molecular mass significantly, suggesting they were not used for glycosylation or only limited carbohydrate moieties were added at these sites. This novel method can serve as a powerful tool to study the biological phenotypes of genes whose functions are determined by multiple sites. PMID- 20362003 TI - Detecting Sugarcane yellow leaf virus infection in asymptomatic leaves with hyperspectral remote sensing and associated leaf pigment changes. AB - Sugarcane infected with Sugarcane yellow leaf virus (SCYLV) rarely produces visual symptoms until late in the growing season. High-resolution, hyperspectral reflectance data from SCYLV-infected and non-infected leaves of two cultivars, LCP 85-384 and Ho 95-988, were measured and analyzed on 13 July, 12 October, and 4 November 2005. All plants were asymptomatic. Infection was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Results from discriminant analysis showed that leaf reflectance was effective at predicting SCYLV infection in 73% of the cases in both cultivars using resubstitution and 63% and 62% in LCP 85-384 and Ho 95-988, respectively, using cross-validation. Predictive equations were improved when data from sampling dates were analyzed individually. SCYLV infection influenced the concentration of several leaf pigments including violaxanthin, beta-carotene, neoxanthin, and chlorophyll a. Pigment data were effective at predicting SCYLV infection in 80% of the samples in the combined data set using the derived discriminant function with resubstitution, and 71% with cross-validation. Although further research is needed to improve the accuracy of the predictive equations, the results of this study demonstrate the potential application of hyperspectral remote sensing as a rapid, field-based method of identifying SCYLV-infected sugarcane plants prior to symptom expression. PMID- 20362004 TI - A protein chip designed to differentiate visually antibodies in chickens which were infected by four different viruses. AB - This study aimed to develop a visual protein chip that can differentiate the antibodies induced by avian influenza virus, Newcastle disease virus, infectious bronchitis virus and infectious bursal disease virus, simultaneously. Proteins from the four viruses were purified and spotted onto an aldehyde group-modified glass slide at 2mg/ml. After that, the protein chip was reacted with the corresponding positive serum against these viruses, hybridized with a colloidal gold-labeled secondary antibody and visualized by silver staining. A diagnostic protein chip was constructed to differentiate antibodies of four poultry diseases This protein chip showed good sensitivity compared with traditional methods, and it was more than 400 times as sensitive as the agar gel precipitin methods used to detect avian influenza and infectious bursal disease. The protein chip was used to test known serum samples of the four poultry diseases and field serum samples. The results showed that this method could hybridize specifically with the corresponding antibodies with strong signals and without cross-hybridization. In conclusion, this protein chip can be used to differentiate the antibodies induced by the four avian viruses. PMID- 20362005 TI - Immunochromatographic lateral flow test for detection of antibodies to Equine infectious anemia virus. AB - The purpose of this study was to develop and evaluate a simple immunochromatographic lateral flow (ICLF) test for specific detection of Equine infectious anemia virus (EIAV) antibodies in equine sera. Viral recombinant p26 capsid protein (rp26) was used as the capture protein in the test line and as the detector reagent conjugated to colloidal gold. The performance of rp26-ICLF was evaluated, and the results obtained were compared with a commercially available agar gel immunodiffusion (AGID) test used as a standard of comparison according to international guidelines. The values obtained for comparative diagnostic sensitivity (98.3%), diagnostic specificity (87.4%) and concordance (92.4%) were similar to those reported for other ICLF tests for animal infectious diseases. Very good repeatability and reproducibility, as well as a total agreement with blind previous results from three proficiency test panels, were obtained, thus indicating that rp26-ICLF is a precise test. The end point of the twofold serial dilution of serum samples was the same as, and even better than, the AGID test, thus demonstrating the same analytical sensitivity as that of the reference method for EIA diagnosis. No cross-reactivity was observed when serum samples from horses with other infectious diseases were analyzed. rp26-ICLF proved to be a precise and rapid test suitable for field screening in veterinary practice, since minimal equipment and operator expertise are required. However, further research should be carried out to increase the level of sensitivity. PMID- 20362006 TI - Development of a multiplex real-time RT-PCR assay for detection of influenza A, influenza B, RSV and typing of the 2009-H1N1 influenza virus. AB - A high-throughput real-time RT-PCR assay was developed to amplify and detect a conserved region of the hemagglutinin gene of the 2009-H1N1 influenza A virus using a minor groove binder-conjugated hybridization probe. The assay was paired with a separate triplex real-time assay that detects influenza A via the matrix gene, influenza B and RSV in a multiplex format and compared with the Centers for Disease Control and Prevention (CDC) rRT-PCR assay using 143 samples. The 2009 H1N1 portion of the multiplex assay had 100% correlation with the CDC assay, while the triplex assay had a 99% agreement. An additional 105 samples collected from October to November 2009 were also tested using both the individual 2009 H1N1 and triplex assays. Of these 105 samples, eight were positive for the hemagglutinin target in the H1N1 assay and negative for the matrix target in the triplex assay. Discrepant analysis revealed single nucleotide polymorphisms within the matrix gene of 2009-H1N1 virus-positive samples. The limit of detection for the 2009-H1N1 assay was between 750 and 1,500 copies/reaction and no cross-reactivity with other respiratory pathogens was observed. Overall, this multiplexed format proved to be sensitive, robust and easy to use and serves as a useful tool for pandemic testing. PMID- 20362007 TI - Isolation and characterization of the first Chinese strain of porcine Teschovirus 8. AB - Investigations were carried out to identify the causal agent of acute diarrhea, respiratory distress, and death of pigs on a swine farm in Jilin Province, northern China. Only porcine Teschovirus (PTV, designated as PTV-8 Jilin/2003) was isolated from samples of organs. The presence of PTV was confirmed by the production of a specific cytopathic effect on susceptible cells and by the results of the immunoperoxidase monolayer assay (IPMA), polymerase chain reaction, and electron microscopy. Other pathogenic agents causing diarrhea, respiratory distress, and death (including porcine rotavirus, transmissible gastroenteritis virus of swine, porcine epidemic diarrhea virus, classical swine fever virus, pseudorabies virus, porcine circovirus, porcine reproductive and respiratory syndrome virus, Japanese encephalitis virus, Mycoplasma, Leptospira, Streptococcus, Listeria, and Brucella species) were excluded as possible causal agents because they were not associated consistently with the disease of the pigs. PTV-8 Jilin/2003 was adapted to grow in swine primary kidney (PK-15) cells and in a swine testicular cell line (ST cells). When inoculated into healthy pigs, PTV-8 Jilin/2003 caused the same symptoms as those observed in the affected herd. It is concluded that PTV-8 Jilin/2003 was the causal agent of this disease. PMID- 20362008 TI - Evaluation of various real-time RT-PCR assays for the detection and quantitation of human norovirus. AB - Human noroviruses (NoVs) are the most common viruses causing acute gastroenteritis in humans. Performance characteristics of two commercial quantitative NoV RT-PCR assays, the Norovirus real-time RT-PCR Kit (AnDiaTec) and the Type I and Type II kits (Generon), and the international assay as selected by the CEN/TC/WG6/TAG4 group were evaluated for the specific detection and quantitation of 59 NoV samples, including different subtypes of NoV genogroup I and II. The results showed that the method proposed by the CEN/TC/WG6/TAG4 group was 100% specific since it was able to detect all samples tested. The commercialized kits evaluated failed to detect a vast majority of NoV GI strains. Additionally the Generon kit did not succeed to detect strains from GII.3, GII.5, GII.6, GII.7, GII.8, GII.12 and GII.17. In addition, the detection limit using the most prevalent strain, NoV GII.4, was 2.5 PCRU per reaction using both commercial kits. Despite this good sensitivity for NoV GII.4 detection it is concluded that both commercial assays are not suitable for the detection and quantitation of most NoV subtypes. Therefore the method proposed by the CEN/TC/WG6/TAG4 group is recommended for epidemiological studies and outbreaks investigations. PMID- 20362009 TI - A multicenter evaluation of the Abbott RealTime HCV Genotype II assay. AB - Genotype determination is recommended before starting anti-HCV therapy to determine the duration of treatment (PEG-Interferon+ribavirin). The Versant HCV Genotype 2.0 assay, based on the reverse hybridization of the 5'UTR segment and core region of hepatitis C virus (HCV), has been one of the assays used most widely for HCV genotyping. A multicenter evaluation of the more automated Abbott RealTime HCV Genotype II assay was carried out on 124 HCV positive sera tested previously with the Versant HCV Genotype 2.0 assay. There was good agreement between the two assays. Type concordance was 95.9% (117/122) while concordance at the subtype level for genotype 1 was 95.6% (43/45). The Abbott RealTime HCV Genotype II assay is automated, allowing a substantial reduction of time-to results and hands-on time. The combined features of full automation, objective interpretation and digital archiving make this assay useful in a diagnostic setting. PMID- 20362010 TI - A vaccinia-virus-free reverse genetics system for infectious hematopoietic necrosis virus. AB - Reverse genetics system is a powerful tool to study the function of a particular gene. The currently available reverse genetics system for Novirhabdovirus is based on vaccinia-driven T7 RNA polymerase expression. An improved system for the recovery of infectious hematopoietic necrosis virus (IHNV) was developed which utilizes cellular RNA polymerase II machinery for transcription. A full-length cDNA clone of IHNV, flanked by hammerhead ribozyme and hepatitis delta ribozyme sequences, was assembled in an expression plasmid under the control of a cytomegalovirus promoter. Transfection of this full-length plasmid along with the supporting plasmids (N, P, NV and L) into epithelioma papulosum cyprini cells resulted in the recovery of a viable recombinant IHNV (rIHNV). The authenticity of rIHNV was confirmed by the presence of restriction sites introduced artificially in the genome. A recombinant IHNV expressing a foreign gene - enhanced green fluorescent protein - was also recovered. The recovered IHNVs showed similar growth characteristics as the parental IHNV in cell cultures. Challenge of susceptible rainbow trout with wild-type IHNV and rIHNV induced clinical disease signs indistinguishable from the parental strain and produced mortality. Thus, a vaccinia-virus-free reverse genetics system described for IHNV is applicable for the recovery of any Novirhabdovirus, which will facilitate studies on viral pathogenesis and the design of new generation of viral vectored vaccines. PMID- 20362011 TI - Some appetitive procedures for examining associative learning in the mouse: Implications for psychopathology. AB - There are few demonstrations of basic associative learning phenomena using appetitive procedures in mice. This article describes procedures for obtaining four associative learning phenomena in mice, using an appetitive conditioning procedure in which the reinforcer was delivery of a sucrose pellet, and the conditioned response head entry into the food tray. Experiment 1 demonstrated latent inhibition in a within-subjects procedure. Experiment 2 demonstrates both overshadowing and blocking, and Experiment 3 Pavlovian conditioned inhibition, which was evaluated by both summation and retardation tests. These procedures all have potential relevance to current translational research questions. The specific advantages of using appetitive tasks are discussed. PMID- 20362012 TI - Acoustic tone or medial geniculate stimulation cue training in the rat is associated with neocortical neuroplasticity and reduced akinesia under haloperidol challenge. AB - Sensory cues can improve movement deficits in Parkinson's disease, but little is known about the mechanisms involved. To investigate neuroplastic changes following sensorimotor cue training, rats were shaped to respond to acoustic tone or medial geniculate stimulation cues by retrieving a food reward. Neuroplasticity associated with training was assessed by changes in auditory neocortical evoked field potentials and dendritic morphology. Stimulation cue training was associated with changes in dendritic arbour length and complexity in auditory and motor neocortices, but was without effect on evoked electrophysiological responses. Tone cue training was associated with a significant increase in peak height of the evoked auditory response and then under haloperidol challenge, demonstrated reduced akinesia. Results indicate that cue-training induces neuroplastic changes that may be related to improved sensorimotor function under dopaminergic antagonism. PMID- 20362013 TI - Tissue distribution and effects of fasting and obesity on the ghrelin axis in mice. AB - Ghrelin is a 28 amino acid peptide hormone derived from the 117 amino acid proghrelin, following cleavage by proprotein convertase 1 (PC1). In this study, we comprehensively assessed the tissue distribution and the effect of fasting and obesity on preproghrelin, Exon-4D, PC1 and GOAT expression and proghrelin-derived peptide (PGDP) secretion. The stomach was the major source of preproghrelin expression and PDGPs, followed by the small intestine. The remaining peripheral tissues (including the brain and pancreas) contained negligible expression levels. We detected obestatin in all stomach proghrelin cells, however, 22% of proghrelin cells in the small intestine did not express obestatin. There were strain differences in ghrelin secretion in response to fasting between CD1 and C57BL/6 mice. After a 24 hour-fast, CD1 mice had increased plasma levels of total ghrelin and obestatin with no change in preproghrelin mRNA or PGDP tissues levels. C57BL/6 mice showed a different response to a 24 hour-fast having increased proghrelin mRNA expression, stomach acylated ghrelin peptide and no change in plasma obestatin in C57BL/6 mice. In obese mice (ob/ob and diet-induced obesity (DIO)) there was a significant increase in preproghrelin mRNA levels while tissue and plasma PGDP levels were significantly reduced. Fasting did not affect PGDP in obese mice. Obese models displayed differences in GOAT expression, which was elevated in DIO mice, but reduced in ob/ob mice. We did not find co localization of the leptin receptor in ghrelin expressing stomach cells, ruling out a direct effect of leptin on stomach ghrelin synthesis and secretion. PMID- 20362014 TI - Development and validation of a resistance and virulence gene microarray targeting Escherichia coli and Salmonella enterica. AB - A microarray was developed to simultaneously screen Escherichia coli and Salmonella enterica for multiple genetic traits. The final array included 203 60 mer oligonucleotide probes, including 117 for resistance genes, 16 for virulence genes, 25 for replicon markers, and 45 other markers. Validity of the array was tested by assessing inter-laboratory agreement among four collaborating groups using a blinded study design. Internal validation indicated that the assay was reliable (area under the receiver-operator characteristic curve=0.97). Inter laboratory agreement, however, was poor when estimated using the intraclass correlation coefficient, which ranged from 0.27 (95% confidence interval 0.24, 0.29) to 0.29 (0.23, 0.34). These findings suggest that extensive testing and procedure standardization will be needed before bacterial genotyping arrays can be readily shared between laboratories. PMID- 20362015 TI - Behavioral and evoked potential measures of distraction in 5-year-old children born preterm. AB - Executive and attention dysfunctions are common in very preterm children. We studied their involuntary attention process by using behavioral measurements and auditory event-related potentials (AERP) with a distraction paradigm at age five years. The active task was to distinguish between two animal sounds. As an irrelevant feature the sounds were presented from frequent (standard) or infrequent (deviant, 11%) direction from two loudspeakers. Of the 28 preterm children, only 75% could accomplish the task, whereas all full-term children (n=15) could. When distinguishing the animal sounds, the reaction times were longer to the sounds from the deviant than from the standard direction in both groups, indicating involuntary distraction. The hit rates for the sounds from standard and deviant directions were similar in both groups. AERP amplitudes in the P1 interval and in the P3a interval elicited by standard and deviant stimuli were smaller in the preterm than in the control children. Deviants elicited P3a (indicating attentional orienting) and reorienting negativity (indicating attentional reorienting after distraction) in both groups. Comparable involuntary attentional orienting, distraction, and reorienting suggest similar maturation processes in 5-year-old preterm and full-term children. However, smaller AERP amplitudes in P1 and P3a interval suggest altered processing of auditory stimuli in those born preterm. As one-fourth of the preterm children could not accomplish the paradigm, less demanding paradigms should be used in studying children with increased distractibility. PMID- 20362016 TI - Varying required effort during interference control in children with AD/HD: task performance and ERPs. AB - Prominent models of attention-deficit/hyperactivity disorder (AD/HD) contend that disinhibition is the core deficit, or that any inhibition deficits that exist are secondary to dysfunctional energetic regulation (i.e. effort and arousal). This study tested these models by investigating the influence of task-directed effort, as manipulated by stimulus degradation, on interference control deficits in children with AD/HD. Twenty children with AD/HD aged between 7 and 14years were matched in age to 20 controls and performed a modified visual Eriksen flanker task, while EEG and skin conductance level (SCL) were recorded. Participants completed the task under three conditions varying in stimulus degradation: none, 30% or 60%. Results revealed a quadratic effect with improved task performance in the 30% degradation condition, relative to the other conditions. Overall, children with AD/HD showed a tendency towards increased errors and more variable responding, although this did not differ between conditions. Importantly, children with AD/HD showed no deficits in interference control at a behavioural level. SCL revealed reduced activity in the AD/HD group during the non-degraded condition which normalised to control levels in the highest degradation condition. ERPs revealed two functionally distinct N2 components, one of which, along with the P3, was larger to incongruent stimuli, consistent with previous studies linking this component to inhibitory processing. Atypical activation of these components was evident in children with AD/HD and occurred as a function of degradation condition. Taken together these findings suggest the role of other factors such as state regulation as underlying deficits in AD/HD. PMID- 20362017 TI - Effect of an intraduodenal injection of fat on the activities of the adrenal efferent sympathetic nerve and the gastric efferent parasympathetic nerve in urethane-anesthetized rats. AB - Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, epsilon-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs-the degradation products of fats-in the intestinal lumen. PMID- 20362018 TI - Functional analysis of the orf390 gene of the white spot syndrome virus. AB - orf390 (WSSV449) is a novel apoptosis inhibitor gene in the genome of the White Spot Syndrome Virus (WSSV). In the present study, we focus on the function of orf390 gene. Stable expression of orf390 prevented SF9 insect cells from undergoing actinomycin D-induced apoptosis. ORF390 also rescued the replication of a p35-deficient-mutant (AcMNPVDeltap35k/pol+) in SF9 cells. In addition, ORF390 inhibits the activities of caspase-3 and -9 in vivo and in vitro. Here we demonstrate that the anti-apoptotic activity of ORF390 is dependent on two putative caspase-9 cleavage sites (VETD233 downward arrowG and LEHD303 downward arrowG) and one caspase-3 cleavage site (DEVD272 downward arrowG). Our results support the conclusion that these three sites play a key role in the suppression of apoptosis mediated by ORF390. These data further suggest that orf390 encodes a novel anti-apoptotic protein involved in cell survival and apoptosis regulation. PMID- 20362019 TI - A novel approach to deliver anticancer drugs to key cell types in tumors using a PDGF receptor-binding cyclic peptide containing carrier. AB - Tumor stromal cells have been recently recognized to contribute to tumor growth. Therefore, we hypothesized that delivery of anticancer drugs to these cells in addition to the tumor cells might treat cancer more effectively. Stromal cells abundantly expressed Platelet-Derived Growth Factor Receptor-beta (PDGFR-beta) in different human tumors as shown with immunohistochemistry. To achieve targeting through PDGFR-beta, we developed a carrier by modifying albumin with a PDGFR-beta recognizing cyclic peptide (pPB-HSA). pPB-HSA specifically bound to PDGFR-beta expressing 3T3 fibroblasts, C26 and A2780 cancer cells in vitro. Subsequently, doxorubicin was conjugated to pPB-HSA through an acid-sensitive hydrazone linkage. In vitro, Dox-HSA-pPB was taken up by fibroblasts and tumor cells and a short exposure of the conjugate induced cell death in these cells. In vivo, the conjugate rapidly accumulated into PDGFR-beta expressing cells in C26 tumors. Treatment with Dox-HSA-pPB significantly reduced the C26 tumor growth in mice while free doxorubicin treated mice had lower response to the therapy. Furthermore, in contrast to free doxorubicin the conjugate did not induce loss in body weight. In conclusion, the present study reveals a novel approach to target key cell types in tumors through PDGFR-beta, which can be applied to enhance the therapeutic efficacy of anticancer drugs. PMID- 20362020 TI - Downregulation of EGFR by a novel multivalent nanobody-liposome platform. AB - The epidermal growth factor receptor (EGFR) is a recognized target for tumor therapy and monoclonal antibodies (mAbs, e.g. cetuximab) have been developed to inhibit receptor activation. Besides blocking ligand (e.g. EGF) binding to the receptor, reports have shown that mAbs promote slow receptor internalization and degradation in lysosomes, i.e. downregulation. The efficacy of receptor downregulation was recently shown to depend on the size of receptor clusters formed at the cell surface. In this study, a multivalent platform is presented, consisting of nanobodies recognizing the ectodomain of EGFR (EGa1) coupled to PEG liposomes, and the in vitro and in vivo effects of this system on EGFR internalization and downregulation were investigated. Nanobodies are the smallest functional antigen-binding immunoglobulin fragments and the EGa1 nanobody has been described as an EGFR-antagonist. EGa1-liposomes (EGa1-L) induced a more than 90% removal of EGFR from the cell surface, as a result of receptor internalization. Furthermore, this massive sequestration of EGFR mediated by EGa1 L lead to receptor degradation, while no degradation was detected with the monovalent nanobody. The downregulatory capacity here reported was found to be independent of the epitope on EGFR recognized by the grafted nanobody, and exclusive to the nanobody-liposomes, as anti-EGFR single chain variable fragments (scFv) coupled to liposomes were unable to induce this effect. Importantly, EGa1 L induced a significant inhibition of tumor cell proliferation, in vitro, an effect likely mediated by the combination of receptor downregulation and receptor antagonism. Also in vivo, EGFR downregulation was observed in tumors of mice intravenously injected with EGa1-L, indicating that this multivalent platform blocks ligand binding to the receptor and simultaneously induces the downregulation of EGFR. PMID- 20362021 TI - A non-covalent strategy combining cationic lipids and CPPs to enhance the delivery of splice correcting oligonucleotides. AB - Modulation of pre-mRNA splicing by steric-block oligonucleotides constitutes a promising strategy for the treatment of many diseases, but requires efficient delivery to cell nuclei. In the present study, we evaluated the efficacy of a non covalent strategy that combines a cell penetrating peptide with a lipoplex-based formulation to mediate the delivery of splice-switching oligonucleotides. The splice correcting ability of these new formulations was assessed using splice switching oligonucleotides targeted towards the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc/705 splice correction model. Importantly, the optimal splice correcting activity was exhibited by the formulation containing both lipid and peptide components, the order of component addition in these formulations being crucial for their efficacy. Our results demonstrate that the inclusion of cationic liposomes in the formulation provides the ability to improve release from endocytic vesicles, a barrier that severely limits the efficiency of oligonucleotide delivery by cell penetrating peptides. On the other hand, cell penetrating peptides potentiate the cellular uptake and delivery of the oligonucleotides by the lipoplexes. Moreover, when combining cell penetrating peptides with the lipoplex formulations, a significant reduction in the amount of required cationic lipid could be achieved, while maintaining or even enhancing biological activity. PMID- 20362022 TI - Maternal encouragement to be thin moderates the effect of commercials on children's snack food intake. AB - The present study experimentally tested the effects of adult targeted food commercials (energy-dense and light food products) on actual snack food intake in young children while watching television. Furthermore, the moderating role of maternal behaviors was investigated. The children (N=121, aged between 8 and 12 years) were exposed to a neutral movie that was interrupted by two commercial breaks. These breaks contained commercials promoting either energy-dense foods, low energy versions of the same energy-dense foods (light food commercials), or neutral commercials aimed at adults. Snack food intake during watching television was measured. Children filled out questionnaires and were weighed and measured afterwards. Children who perceived maternal encouragement to be thin ate slightly more when exposed to energy-dense food commercials and especially when exposed to light food commercials than when exposed to neutral commercials. In contrast, children who perceived no maternal encouragement to be thin ate more when exposed to neutral commercials than when exposed to either energy-dense food commercials or light food commercials. These findings suggest that exposure to adult targeted light food cues produced disinhibition in children who experienced maternal encouragement to be thin, resulting in elevated snack food intake. PMID- 20362023 TI - H2O2 and PAF mediate Abeta1-42-induced Ca2+ dyshomeostasis that is blocked by EGb761. AB - Calcium (Ca2+) dyshomeostasis may be of pivotal importance in mediating the neurotoxic action of amyloid beta peptide (Abeta), but the mechanism whereby Abeta disrupts Ca2+ homeostasis remains unclear. Using hippocampal neuronal cultures, the present study investigated possible mechanisms underlying Ca2+ dyshomeostasis induced by the oligomeric form of Abeta1-42 and two possible mediators of its toxicity, hydrogen peroxide (H2O2) and platelet-activating factor (PAF). It was found that, both H2O2 and PAF were able to reproduce each of the events induced by oligomeric Abeta1-42, including (a) Ca2+ influx via N methyl-D-aspartic acid (NMDA) receptors, (b) enhancement of Ca2+ response to NMDA via activation of protein kinase C (PKC), (c) the increase of extracellular concentrations of glutamate and (d) the increase in cytosolic free Ca2+ ([Ca2+]i). Moreover, each of these events could be blocked by Ginkgo biloba extract EGb761, a free radical scavenger with PAF antagonism, and by quercetin, a constituent with well-established free radical scavenging property. In contrast, ginkgolide B, another constituent of EGb761 with well-established PAF antagonizing activity protected the neurons against Ca2+ dyshomeostasis induced by Abeta1-42 and PAF, but not by H2O2. These results suggested the possibility that Abeta1-42-induced Ca2+ dyshomeostasis might be mediated by formation of toxic mediators such as H2O2 and PAF. Therefore, increased production of toxic mediators such as H2O2 and PAF in the brain may be critical in the pathological mechanism of neurodegenerative diseases, particularly Alzheimer's disease (AD), and may serve as major therapeutic targets for these diseases. PMID- 20362024 TI - Characterization of neuronal and astroglial responses to ER stress in the hippocampal CA1 area in mice following transient forebrain ischemia. AB - Transient forebrain ischemia has been shown to cause neuronal injury in the CA1 area of the hippocampus in mice. In addition to neuronal injury, astrocytes in area CA1 undergo apoptosis under ischemic conditions. Although failure of impaired astrocytes to take up glutamate is thought to contribute to the pathogenesis of cerebral ischemia, the molecular mechanism underlying this phenomenon remains unexplored. In the present study, we investigated neuronal and astroglial responses to endoplasmic reticulum (ER) stress, which is an important sequela of transient forebrain ischemia in the hippocampus of mice. Cellular injury was observed in area CA1 of the hippocampus 72h after reperfusion, and ssDNA positivity was detectable in some glial cells as well as neurons in this area. An increase of 78-kDa glucose-regulated protein (GRP78), an indicator of ER stress, was detected in pyramidal neurons and astrocytes in this area after the insult. Immunohistochemical analysis showed that caspase-12 was increased in pyramidal neurons and astrocytes located in the extrapyramidal cell layer. Immunoreactivity for C/EBP homologous protein (CHOP) was increased significantly in pyramidal cells but not in astrocytes. These results suggest that astrocytes as well as pyramidal neurons in area CA1 undergo apoptosis through an ER stress dependent mechanism after ischemia. Unlike the situation in neuronal apoptosis, CHOP does not play a role in the cell death of astrocytes. PMID- 20362025 TI - Positive reinforcing effects of flupirtine--two case reports. PMID- 20362026 TI - Cocaine and amphetamine regulated transcript (CART) gene in the comorbidity of schizophrenia with alcohol use disorders and nicotine dependence. AB - Studies have shown a genetic susceptibility to develop schizophrenia, alcohol use disorders and nicotine dependence. Brain areas related to reward and reinforcement show high expression of the cocaine and amphetamine regulated transcript (CART). Nicotine and alcohol are also able to modulate CART expression in the hypothalamic areas. In this study, we evaluated whether CART variants would influence the predisposition of schizophrenia subjects to alcohol use disorders and nicotine dependence. Clinical and genetic data were obtained from 190 unrelated Caucasian schizophrenia subjects collected at the Centre for Addiction and Mental Health. We found no association of CART variants with alcohol use disorders or nicotine dependence. We found a trend for allelic association of rs11575893 with the heaviness of smoking behaviour (p=0.057). Our results indicate that genetic variants in the CART gene may not play a major role in the vulnerability of schizophrenia subjects to concurrent alcohol use disorders and nicotine dependence. Additional association studies in independent samples can evaluate whether CART gene is playing a role in the schizophrenia comorbidity with alcohol use disorders and nicotine dependence. PMID- 20362027 TI - Influence of chrysin on hepatic marker enzymes and lipid profile against D galactosamine-induced hepatotoxicity rats. AB - Chrysin is a flavonoid that exists in nature and is the major component of some traditional medicinal herbs. We investigated the hepatoprotective and antihyperlipidaemic potential of chrysin against D-galactosamine (a single intraperitoneal injection 400 mg/kg BW) induced hepatotoxicity in male albino Wistar rats. D-GalN rats exhibited an increased hepato and nephro toxicity marker activities aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase and total bilirubin level while urea, uric acid and creatinine and lipid profile. It also negatively affected the serum total protein, albumin and A/G ratio. Rats treated with chrysin at different concentrations (25, 50 and 100 mg/kg BW) caused a significant improvement in serum protein level, decreased hepato and nephro toxicity markers. It also decreased the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol while high density lipoprotein cholesterol significantly increased. It also decreased the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney. The effect of chrysin (25 mg/kg) is comparable with silymarin, a known hepatoprotective drug. Chrysin thus exhibits hepatoprotective and antihyperlipidaemic activity. PMID- 20362028 TI - Emerging roles for phospholipase A2 enzymes in cancer. AB - Phospholipase A(2) (PLA(2)) enzymes (EC3.1.4.4) regulate the release of biologically active fatty acids and lysophospholipids from membrane phospholipid pools. These lipids are also substrates for intracellular biochemical pathways that generate potent autocrine and paracrine lipid mediators such as the eicosanoids and platelet activating factor. These factors, in turn, regulate cell proliferation, survival, differentiation, motility, tissue vascularisation, and immune surveillance in virtually all tissues, functions that are subverted by cancer cells for tumour growth and metastasis. Thus the relevance of PLA(2) dependent pathways to the genesis and progression of cancer has been of interest since their discovery and with recent technological advances, their role in tumourigenesis has become more tractable experimentally. Limited human genetic studies have not yet identified PLA(2) enzymes as classical mutated oncogenes or tumour suppressor genes. However, there is strong evidence that of the 22 identified human PLA(2) enzymes, ten of which have been studied in cancer to date, most are aberrantly expressed in a proportion of tumours derived from diverse organs. Correlative and functional studies implicate the expression of some secreted enzymes (sPLA(2)s), particularly the best studied enzyme Group IIA sPLA(2) in either tumour promotion or inhibition, depending on the organ involved and the biochemical microenvironment of tumours. As in immune-mediated inflammatory pathologies, genetic deletion studies in mice, supported by limited studies with human cells and tissues, have identified an important role for Group IVA PLA(2) in regulating certain cancers. Pharmacological intervention studies in prostate cancer suggest that hGIIA-dependent tumour growth is dependent on indirect regulation of Group IVA PLA(2). Group VI calcium-independent PLA(2) enzymes have also been recently implicated in tumourigenesis with in vitro studies suggesting multiple possible roles for these enzymes. Though apparently complex, further characterization of the regulatory relationships amongst PLA(2) enzymes, lipid mediator biosynthetic enzymes and the lipid mediators they produce during tumour progression is required to define the biochemical context in which the enzymes modulate cancer growth and development. PMID- 20362029 TI - Combination of DEC plus aspirin induced mitochondrial mediated apoptosis in filarial parasite Setaria cervi. AB - Diethylcarbamazine (DEC) is the main drug used against lymphatic filariasis but it is only microfilaricidal. Hence there is an urgent need for adulticidal drug. Aspirin is known nonsteroidal anti-inflammatory drugs which can inhibit prostaglandin H synthase and also induces apoptosis. Studies presented in this paper demonstrated that exposure of worms to the combination of DEC plus aspirin (DEC + A) at 100 microM concentration irreversibly paralyzed adult worms as well as microfilariae within 2 h. Some of the apoptosis markers viz; DNA fragmentation with accompanying ladder formation, upregulation of Bax expression and decrease in Bcl-2 have suggested that the parasite may be killed due to mitochondrial mediated apoptosis. The levels of several apoptosis regulating proteins and enzymes have also shown to be altered. DEC + A treated worms showed significant decrease in prostaglandin H synthase activity (PGHS) and increase in the level of nitric oxide (NO) and cysteine proteases while glutathione (GSH) and peroxidase level was found to be decreased. NO is known inducer of mitochondrial mediated apoptosis and acts by increasing the permeability of mitochondrial membrane through Bax and allowing cytochrome c to release in cytosol, inducing caspases leading to apoptosis. The DEC + A concentration used in this study is much lower than recommended dose so its intake is safe. Here we report for the first time that combination of DEC and aspirin is more effective and could be used as an adulticidal for control of human filarial infections. PMID- 20362030 TI - Derivation of multipotent progenitors from human circulating CD14+ monocytes. AB - Circulating CD14(+) monocytes are originated from hematopoietic stem cells in the bone marrow and believed to be committed precursors for phagocytes, such as macrophages. Recently, we have reported a primitive cell population termed monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14(+) monocytes, but circulating precursors for MOMCs still remain undetermined. Comparative analysis of gene expression profiles of MOMCs and other monocyte-derived cells has revealed that embryonic stem cell markers, Nanog and Oct-4, are specifically expressed by MOMCs. In vitro generation of MOMCs requires binding to fibronectin and exposure to soluble factors derived from activated platelets. MOMCs contain progenitors with capacity to differentiate into a variety of nonphagocytes, including bone, cartilage, fat, skeletal and cardiac muscle, neuron, and endothelium, indicating that circulating monocytes are more multipotent than previously thought. In addition, MOMCs are capable of promoting ex vivo expansion of human hematopoietic progenitor cells through direct cell-to-cell contact and secretion of a variety of hematopoietic growth factors. These findings obtained from the research on MOMCs indicate that CD14(+) monocytes in circulation are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue. PMID- 20362031 TI - Activation of Ras-dependent Elk-1 activity by MLL-AF4 family fusion oncoproteins. AB - OBJECTIVE: Mixed lineage leukemia (MLL) gene rearrangement is commonly observed in human leukemias. Many of the resultant MLL fusion proteins are found correlated with Ras signaling. Nevertheless, Ras mutations have only been reported in a small subset of MLL-rearranged leukemia. With the potential of developing new therapeutic regimens targeting Ras signaling pathway, we studied the role of MLL-AF4 family fusions and MLL-septin family fusions in the activation of Ras signaling in leukemogenesis. MATERIALS AND METHODS: Elk-1 driven luciferase reporter system was used to study the role of MLL-AF4, MLL AF5q31, MLL-LAF4, MLL-CDCrel, MLL-MSF, and MLL-Septin 6 in the activation of Ras signaling. Dominant negative Ras S17N mutant and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor U0126 were employed to demonstrate the involvement of Ras and MEK in this transactivation event. The activation of endogenous Ras/MEK signaling pathway by MLL fusion proteins in leukemia cell lines was also addressed by immunoblot analysis and small interfering RNA knockdown approach. RESULTS: We demonstrated that MLL-AF4, MLL-AF5q31, and MLL-LAF4 activated Elk-1 transcription factor, one of the major downstream effectors of Ras. This activation was abolished in the presence of dominant negative Ras or MEK inhibitor U0126, indicating the requirements of Ras and MEK. We further showed that endogenous MEK is phosphorylated in a MLL-AF4 expressing leukemia cell line, whereas depletion of MLL-AF4 by small interfering RNA reduced the phospho-MEK level. CONCLUSION: Our findings suggest that MLL-AF4 family fusion oncoproteins can activate Elk-1 through Ras/MEK/extracellular signal-regulated kinase (ERK) pathway and strongly support the role of Ras signaling in the pathogenesis of MLL-rearranged leukemia. PMID- 20362032 TI - Magnetic resonance spectroscopy of the brain under mild hypothermia indicates changes in neuroprotection-related metabolites. AB - Brain hypothermia has demonstrated pronounced neuroprotective effect in patients with cardiac arrest, ischemia and acute liver failure. However, its underlying neuroprotective mechanisms remain to be elucidated in order to improve therapeutic outcomes. Single voxel proton magnetic resonance spectroscopy ((1)H MRS) was performed using a 7 Tesla MRI scanner on normal Sprague-Dawley rats (N=8) in the same voxel under normothermia (36.5 degrees C) and 30min mild hypothermia (33.5 degrees C). Levels of various brain proton metabolites were compared. The level of lactate (Lac) and myo-inositol (mI) increased in the cortex during hypothermia. In the thalamus, taurine (Tau), a cryogen in brain, increased and choline (Cho) decreased. These metabolic alterations indicated the onset of a number of neuroprotective processes that include attenuation of energy metabolism, excitotoxic pathways, brain osmolytes and thermoregulation, thus protecting neuronal cells from damage. These experimental findings demonstrated that (1)H-MRS can be applied to investigate the changes of specific metabolites and corresponding neuroprotection mechanisms in vivo noninvasively, and ultimately improve our basic understanding of hypothermia and ability to optimize its therapeutic efficacy. PMID- 20362033 TI - Transpupillary thermotherapy: new observations on neuroprotection of retinal ganglion cells. PMID- 20362034 TI - Psychostimulants given in adolescence modulate their effects in adulthood using the open field and the wheel-running assays. AB - Acute and chronic methylphenidate (MPD) were given to adults treated with MPD only in adulthood (adult I) and to adults that had been treated repeatedly during adolescence and adulthood (adult II). Two locomotor activity assays, the open field and the running wheel, were used in a dose response experiment to assess whether methylphenidate (MPD) treatment during adolescence would affect responses to MPD in adulthood. Each experiment lasted 11 days as follows: saline control on experimental day 1 (ED 1), followed by a single daily dose of saline, 0.6, 2.5, or 10mg/kg MPD for 6 days (ED 2 to ED 7), 3 washout days with no drug administration (ED 8 to ED 10), and saline or MPD challenge on ED 11 at a dose identical to that given on ED 2 to ED 7. Acute MPD elicited characteristic dose response increases in locomotion in both experimental assays of adult I and adult II groups. Adult I and adult II rats tested in the open field assay exhibited sensitization to 2.5mg/kg MPD and tolerance to 10mg/kg MPD, while in the wheel running assay all the three MPD doses elicited sensitization in both adult I and adult II rats. MPD treatment in adolescence did not change the baseline activity when animal reached adulthood. However, the responses to MPD in adult II rat groups were significantly different from the adult I group. Similar observations were noted during washout days. At the low and moderate MPD treatment both experimental assay exhibited similar observations while following the high dose of MPD treatment, the open field assay indicated that tolerance to MPD was expressed, while the wheel-running assay indicated that behavioral sensitization was developed. The distinction between the two assays and adult I and II differences are discussed. PMID- 20362035 TI - Rapid profiling and target analysis of principal components in Fuling Decoctions by UFLC-DAD-ESI-MS. AB - The traditional Chinese medicine formula Fuling Decoction (FD) has been clinically used for eczema treatment, but the unclear chemical distribution and the lack of quality control have strongly restricted its application. In this study, an analytical method incorporating ultra-fast liquid chromatography (UFLC) with MS and UV detection was developed for rapid profiling of the chemical constitutes from FD. Fourteen constitutes were identified by UFLC-ESI-MS, while four major components including genipingentiobioside, geniposide, paeoniflorin and liquiritin were quantified simultaneously by UFLC-DAD. The UFLC-based method was fully validated and can be applied to screening and determination of principal components in commercially FD prescriptions. PMID- 20362036 TI - Bioactive 2-arylbenzofuran derivatives from Morus wittiorum. AB - Investigation of an ethanol extract from the stem bark of Morus wittiorum led to the isolation of five new 2-arylbenzofuran derivatives that were named wittifuran S, wittifuran T, wittifuran V, wittifuran W and wittifuran X (1-5). Structures were determined on the basis of spectroscopic analysis. Two new wittifurans and five previously isolated compounds were assayed for antioxidant and anti inflammatory activity. PMID- 20362037 TI - A new triterpene glycoside from Centella erecta. AB - A new (2alpha,3beta)-23-sulphonyl-2,3-dihydroxyurs-12-en-28-oic acid O-alpha-L rhamnopyranosyl-(1 -> 4)-O-beta-D-glucopyranosyl-(1 -> 6)-O-beta-D-glucopyranosyl ester (1) together with eighteen known compounds were isolated from Centella erecta (L.f.) Fern. Their structures were elucidated mainly by NMR and HRESIMS, as well as on comparison with the reported data. PMID- 20362038 TI - Isolation and identification of the antibacterial active compound from petroleum ether extract of neem oil. AB - From a petroleum ether extract of neem oil (Azadirachta indica A. Juss) the new tetrahydrofuranyl diester 1 was isolated as an anti-bacterial constituent. 1 showed significant activities against three standard bacterial strains, including Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Salmonella enteritidis CMCC (B) 50041. PMID- 20362039 TI - Molecular characterization and methylation study of matrix gla protein in articular cartilage from pig with osteochondrosis. AB - Osteochondrosis (OC) or leg weakness is an economically important disease of young fast growing pigs and is a concern of animal welfare. The etiology and pathogenesis of osteochondrosis is not fully understood yet, but any abnormalities in the formation of hypertrophic chondrocytes and disrupted blood supply to the growth cartilage are very important predisposing factors. Matrix gla protein (MGP) as a potential calcification inhibitor of extracellular matrix might contribute to the development of OC. Molecular characterization, polymorphisms analysis, methylation at promoter region and expression of MGP gene and protein were performed in both healthy and OC cartilage collected from a DurocxPietrain resource population. The porcine MGP gene consists of 4 exons and 3 introns. The full-length MGP cDNA isolated from articular cartilage consists of 606 bp with a 69-bp 5' UTR, a 312-bp open reading frame with a start codon, a 225 bp 3' UTR. Three single-nucleotide polymorphisms (SNP) were detected in the intron 1 (A-115G, C-1073T and C-1135A) and one in the 3'UTR (C-3767T). The relative abundance of MGP mRNA was lower (P<0.05) in OC compared with healthy cartilage. Moreover, the intensity of MGP band was lower (P<0.05) in OC group when quantified by western blot. Furthermore, one CpG region was identified in MGP promoter and DNA methylation of three CG sites were higher in OC compared with normal cartilage. This suggested that the high DNA methylation at specific CG sites in the MGP promoter might be involved in the down regulation of MGP in OC. Immunofluorescence of normal cartilage collected from pigs of different ages revealed that MGP signals were higher in younger pigs and decreased in the older pigs. The MGP protein was expressed more near to the cartilage canals. These results suggest that the MGP gene might be a potential candidate gene for the development of OC in pigs. PMID- 20362040 TI - Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards. AB - Due to the massive reduction of air-change rates in modern, energy-saving houses and dwellings, the contribution of volatile organic compound (VOCs) emissions from wood-based materials to indoor air quality has become increasingly important. To evaluate toxicity of VOC mixtures typically emitted from pine wood and oriented strand boards (OSB) and their main constituents (selected terpenes and aldehydes), cytotoxicity and genotoxicity were investigated in human A549 lung cells. To facilitate exposure directly via gas phase, a 250 L emission chamber was combined with a Vitrocell exposure system. VOC exposure concentrations were measured by GC/MSD. Biological effects were determined after an exposure time of 1h by measuring cytotoxicity (erythrosine B staining) and genotoxicity (comet assay). Neither cytotoxic nor genotoxic effects were observed for VOC mixtures emitted from pine wood or OSB at loading factors of approximately 13 m(2)/m(3) (worst case conditions) of the panels (with maximum VOC levels of about 80 mg/m(3)) in comparison to clean air. While alpha-pinene and Delta(3)-carene did not induce toxic effects even at exposure concentrations of up to 1800 mg/m(3) and 600 mg/m(3), respectively, hexanal showed a cytotoxic effect at 2000 mg/m(3). The alpha,beta-unsaturated aldehydes 2-heptenal and 2 octenal caused genotoxic effects in concentrations exceeding 100mg/m(3) and 40 mg/m(3), respectively. In conclusion, high concentrations of VOCs and VOC mixtures emitted from pine wood and OSB did not lead to adverse effects in A549 human lung cells even at concentrations 10(2) to 10(5)-fold higher than those found in normal indoor air. Attention must be paid to mutagenic and possibly carcinogenic alpha,beta-unsaturated aldehydes. PMID- 20362041 TI - Transgene expression efficiency from plasmid DNA delivered as a complex with histone H3. AB - The intranuclear disposition of plasmid DNA is extremely important for transgene expression. Exogenous histones have been used as carriers of plasmid DNA in histone-mediated gene delivery. In this study, the effects of exogenous histone H3 complexed with plasmid DNA on transgene expression efficiency were examined. The plasmid-histone complexes in various ratios were transfected into HeLa cells by osmotic pressure. Histone H3 suppressed transgene expression in the nucleus in a dose-dependent manner. Our results suggest that the histone-mediated gene delivery is unlikely to be useful, from the viewpoint of the intranuclear disposition. PMID- 20362042 TI - Optimization and physicochemical characterization of a triamcinolone acetonide loaded NLC for ocular antiangiogenic applications. AB - The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter < 200 nm) with a homogeneous particle size distribution (polydispersity index (PI) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity. PMID- 20362043 TI - Depressant effects of Clinopodium mexicanum Benth. Govaerts (Lamiaceae) on the central nervous system. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of leaves of Clinopodium mexicanum Benth. Goaverts (Lamiaceae), commonly known as "Toronjil de Monte", is used in the Mexican traditional medicine to induce sleep, as well as sedative and analgesic remedy. AIM OF THE STUDY: To evaluate the putative depressant effects of an aqueous extract of the medicinal plant Clinopodium mexicanum on the central nervous system (CNS). MATERIALS AND METHODS: The effects of the extract (AECM) on mice were tested in several animal paradigms, including sodium pentobarbital induced sleep, open field tests, and hole-board tests. The effects of AECM on pentylenetetrazole- and picrotoxin-induced convulsions in mice and on the antithermonociceptive response in the hot-plate paradigm were also tested. Additionally, the active extract (AECM) was analyzed with HPLC-ESI-MS techniques. RESULTS: Mice acutely treated with AECM at 100, 200, 500 and 1000mg/kg doses prolonged the sleeping time induced by sodium pentobarbital (42mg/kg). This extract, at 100 and 200mg/kg doses, showed a sedative effect in the hole-board paradigm and decreased spontaneous activity in mice. AECM at 10, 100 and 200mg/kg prolonged the onset of seizures induced by pentylenetetrazole (90mg/kg) and antagonized tonic convulsions induced by picrotoxin (10mg/kg). Additionally, AECM inhibited the response to a thermonociceptive stimulus. The intraperitoneal AECM treatment produced mortality with an LD(50)=2154mg/kg. Chemical analysis showed that the flavanone glycosides neoponcirin, poncirin, and isonaringenin are the main compounds of the active extract. CONCLUSIONS: This study demonstrates that an acutely administered single dose of an aqueous extract of Clinopodium mexicanum can exert depressant effects on the CNS. These findings are in agreement with the traditional use of Clinopodium mexicanum to induce sleep as well as sedative and analgesic remedy. The chemical analysis of AECM revealed the presence of the flavanone glycosides neoponcirin, poncirin, and isonaringin. PMID- 20362044 TI - Homogeneous, heterogeneous and enzymatic catalysis for transesterification of high free fatty acid oil (waste cooking oil) to biodiesel: a review. AB - In the last few years, biodiesel has emerged as one of the most potential renewable energy to replace current petrol-derived diesel. It is a renewable, biodegradable and non-toxic fuel which can be easily produced through transesterification reaction. However, current commercial usage of refined vegetable oils for biodiesel production is impractical and uneconomical due to high feedstock cost and priority as food resources. Low-grade oil, typically waste cooking oil can be a better alternative; however, the high free fatty acids (FFA) content in waste cooking oil has become the main drawback for this potential feedstock. Therefore, this review paper is aimed to give an overview on the current status of biodiesel production and the potential of waste cooking oil as an alternative feedstock. Advantages and limitations of using homogeneous, heterogeneous and enzymatic transesterification on oil with high FFA (mostly waste cooking oil) are discussed in detail. It was found that using heterogeneous acid catalyst and enzyme are the best option to produce biodiesel from oil with high FFA as compared to the current commercial homogeneous base-catalyzed process. However, these heterogeneous acid and enzyme catalyze system still suffers from serious mass transfer limitation problems and therefore are not favorable for industrial application. Nevertheless, towards the end of this review paper, a few latest technological developments that have the potential to overcome the mass transfer limitation problem such as oscillatory flow reactor (OFR), ultrasonication, microwave reactor and co-solvent are reviewed. With proper research focus and development, waste cooking oil can indeed become the next ideal feedstock for biodiesel. PMID- 20362045 TI - Identification and characterization of Th cell epitopes in MrkD adhesin of Klebsiella pneumoniae. AB - In this study, we identified the Th epitopes in MrkD of Klebsiella pneumoniae, an excellent vaccine candidate antigen. By using the RANKPEP prediction algorithm, we have identified and characterized three Th epitopes within the MrkD antigen, which can be recognized by CD4+ T cells from BALB/c (H-2(d)) mice. They were M(221-235), M(175-189), and M(264-278). These epitopes have important value for studying the immune response of K. pneumoniae infection and for designing effective vaccine against K. pneumoniae. PMID- 20362046 TI - A polymorphism in a staphylococcal enterotoxin receptor gene (T cell receptor BV3 recombination signal sequence) is not associated with unexplained sudden unexpected death in infancy in an Australian cohort. AB - Polymorphisms in genes that influence the expression of toxin receptors could contribute to Sudden Infant Death Syndrome (SIDS) and unexplained Sudden Unexpected Death in Infancy (uSUDI) for which there is evidence of toxin involvement. We aimed to determine whether TCRBV3S1 allele 2 could be involved in a staphylococcal toxic shock hypothesis for uSUDI. Observed frequencies of the TCRBV3S1*2 allele and genotype in 48 Australian uSUDI cases and 96 live comparison infants did not differ. In future the role of other toxin receptor gene polymorphisms deserves investigation. PMID- 20362047 TI - Optimization of chemically defined cell culture media--replacing fetal bovine serum in mammalian in vitro methods. AB - Quality assurance is becoming increasingly important. Good laboratory practice (GLP) and good manufacturing practice (GMP) are now established standards. The biomedical field aims at an increasing reliance on the use of in vitro methods. Cell and tissue culture methods are generally fast, cheap, reproducible and reduce the use of experimental animals. Good cell culture practice (GCCP) is an attempt to develop a common standard for in vitro methods. The implementation of the use of chemically defined media is part of the GCCP. This will decrease the dependence on animal serum, a supplement with an undefined and variable composition. Defined media supplements are commercially available for some cell types. However, information on the formulation by the companies is often limited and such supplements can therefore not be regarded as completely defined. The development of defined media is difficult and often takes place in isolation. A workshop was organised in 2009 in Copenhagen to discuss strategies to improve the development and use of serum-free defined media. In this report, the results from the meeting are discussed and the formulation of a basic serum-free medium is suggested. Furthermore, recommendations are provided to improve information exchange on newly developed serum-free media. PMID- 20362048 TI - Determination of environmentally relevant exposure concentrations of polybrominated diphenyl ethers for in vitro toxicological studies. AB - Toxicological studies at environmentally relevant concentrations are essential for understanding ecotoxic and health risks of pollutants such as polybrominated diphenyl ethers (PBDEs). However, no information is available on what exposure levels of PBDEs in vitro studies are environmentally relevant. We exposed MCF-7, HepG2, H295R and PC12 cells to BDE-47, and measured BDE-47 concentrations in the cells after exposure. We also used the percentile method to summarize literature data on environmental exposure levels of biotic tissues to PBDEs. The exposure concentration that resulted in a BDE-47 burden in cells close to the 90th percentile of PBDEs levels in tissues was assigned as the upper limit for the environmentally relevant concentration. Exposure to 1nM BDE-47 resulted in PBDEs burdens in MCF-7, HepG2 and H295R cells close to the 90th percentile but PBDEs burdens in PC12 cells were higher than the 90th percentile. In consideration of the high exposure levels in PBDE-polluted areas, we concluded that the highest environmentally relevant exposure concentration of PBDEs in culture media should be approximately 10nM for MCF-7, HepG2 and H295R cells, and<10nM for PC12 cells. These results provide an approximate reference for setting environmentally relevant exposure concentrations of PBDEs for studies in vitro. PMID- 20362049 TI - The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: results of test performance and transferability. AB - The need for development and validation of in vitro hormone receptor transactivation assays as important alternative tools to study interactions with sex hormone receptors is outlined by international organisations, as such assays should be included in the OECD conceptual framework for the testing and assessment of endocrine active chemicals. Therefore as part of the European Union (EU)-sponsored 6th framework project ReProTect, the validation study with MELN cells, MCF-7 cells (ER+, estrogen receptor positive) which were stably transfected with the estrogen responsive gene ERE-betaGlob-Luc-SVNeo was set up. Standard operating procedures including a prescreen assay for unknown chemicals, an ER-agonist assay and an ER-antagonist assay were developed at the Flemish Institute for Technological Research, Belgium, and successfully transferred to Bayer Schering Pharma AG, Germany. Test results were obtained for 16 chemicals, and it was demonstrated that the MELN assay is transferable, robust and reproducible which allowed to rank chemical compounds according to their strong to weak affinity for the estrogen-alpha receptor, or identify negative chemicals within the test range up to 10(-5)M. Besides the screening for agonism, we demonstrated the suitability of MELN cells to test for antagonistic activity, which is of added value compared to current validated assays. As the MELN assay successfully passed the first modules of the ECVAM validation procedure, it now should be considered for further steps including the definition of a prediction model and application domain to get it accepted as an alternative screening assay, contributing to the 3R's with a reduction of animal experiments. PMID- 20362050 TI - Development and validation of a multiplex real-time PCR for detection of Clostridium chauvoei and Clostridium septicum. AB - Clostridium chauvoei is the causative agent of blackleg in cattle and sheep. The clinical symptoms of this severe disease are very similar to that of malignant edema (Clostridium septicum), infections of other Clostridium species belonging to the gas edema complex, and anthrax (Bacillus anthracis). C. chauvoei and C. septicum are closely related taxa and share many phenotypic properties hampering diagnosis by using traditional microbiological methods. Thus, there is a need for a fast and reliable identification method for specific detection of both species in clinical samples. The multiplex real-time PCR assay presented here is based on the detection of the spo0A gene and enables the simultaneous identification of C. chauvoei and C. septicum. The assay design includes an amplification control DNA template for the recognition of PCR-inhibitors. Assay validation was performed using a collection of 29 C. chauvoei, 38 C. septicum strains and 26 strains of other Clostridium species. Furthermore, the real-time PCR assay was successfully tested on tissue samples from 19 clinical blackleg cases. The assay allowed the reliable detection of one picogram DNA which represents approximate 239 genome equivalents. PMID- 20362051 TI - A vacuolar-type proton (H+) translocating ATPase alpha subunit encoded by the Hc vha-6 gene of Haemonchus contortus. AB - In the present study, a full-length cDNA (designated Hc-vha-6) inferred to encode an alpha subunit of a vacuolar-type proton translocating adenosine triphosphatase (V-ATPase) was isolated from the parasitic nematode Haemonchus contortus, and characterized. The transcript for Hc-vha-6 was detected in all developmental stages and both sexes of H. contortus. Elements, including two TATA box (TATAA), two inverted CAAT box (ATTGG), five E box (CANNTG) and six GATA as well as five inverse GATA (TTATC) transcription factor motifs, were identified in the non coding region upstream of Hc-vha-6. The open reading frame (ORF) of 2601 nucleotides encoded a protein (Hc-VHA-6) of 866 amino acids and a molecular weight of approximately 98.7 kDa. Comparison with a published protein sequence for a homologue (VPH1P) from yeast showed that Hc-VHA-6 had nine transmembrane domains and the 14 essential amino acid residues associated with enzyme activity, assembly, intracellular and/or membrane targeting. Phylogenetic analyses of selected amino acid sequence data revealed Hc-VHA-6 to be most closely related to VHA-6 of Caenorhabditis elegans. A predictive network analysis inferred that vha 6 interacts with at least seven other genes encoding V-ATPase subunits and a small Rab GTPase. This study provides the first insight into a V-ATPase of parasitic nematodes and a sound basis for future functional genomic work. PMID- 20362052 TI - Mechanical stretch and prostaglandin E2 modulate critical signaling pathways in mouse podocytes. AB - Elevated glomerular capillary pressure (Pgc) and hyperglycemia contribute to glomerular filtration barrier injury observed in diabetic nephropathy (DN). Previous studies showed that hypertensive conditions alone or in combination with a diabetic milieu impact podocyte cellular function which results in podocyte death, detachment or hypertrophy. The present study was aimed at uncovering the initial signaling profile activated by Pgc (mimicked by in vitro mechanical stretch), hyperglycemia (high glucose (HG), 25mM d-glucose) and prostaglandin E(2) (PGE(2)) in conditionally-immortalized mouse podocytes. PGE(2) significantly reduced the active form of AKT by selectively blunting its phosphorylation on S473, but not on T308. AKT inhibition by PGE(2) was reversed following either siRNA-mediated EP(4) knockdown, PKA inhibition (H89), or phosphatase inhibition (orthovanadate). Podocytes treated for 20min with H(2)O(2) (10(-4)M), which mimics reactive oxygen species generation by cells challenged by hyperglycemic or enhanced Pgc conditions, significantly increased the levels of active p38 MAPK, AKT, JNK and ERK1/2. Interestingly, stretch and PGE(2) each significantly reduced H(2)O(2)-mediated AKT phosphorylation and was reversed by pretreatment with orthovanadate while stretch alone reduced GSK-3beta inhibitory phosphorylation at ser-9. Finally, mechanical stretch alone or in combination with HG, induced ERK1/2 and JNK activation, via the EGF receptor since AG1478, a specific EGF receptor kinase inhibitor, blocked this activation. These results show that cellular signaling in podocytes is significantly altered under diabetic conditions (i.e., hyperglycemia and increased Pgc). These changes in MAPKs and AKT activities might impact cellular integrity required for a functional glomerular filtration barrier thereby contributing to the onset of proteinuria in DN. PMID- 20362053 TI - Syndecan-4 and beta1 integrin are regulated by electrical activity in skeletal muscle: Implications for cell adhesion. AB - Syndecan-4 and integrins are involved in the cell migration and adhesion processes in several cell types. Syndecan-4, a transmembrane heparan sulfate proteoglycan, is associated to focal adhesions in adherent cells and has been described as a marker of satellite cells in skeletal muscle. In this tissue, beta1 integrin forms heterodimers with alpha5 and alpha6 during myoblast differentiation and with alpha7 in adult muscle. Here, we show that the levels of these two cell surface membrane molecules are regulated by spontaneous electrical activity during the differentiation of rat primary myoblasts. Syndecan-4 and beta1 integrin protein levels decrease after the inhibition of electrical activity using tetrodotoxin (TTX). Syndecan-4 also decreases substantially in denervated rat tibialis anterior muscle. Indirect immunofluorescence analysis shows that syndecan-4 and beta1 integrin co-localize with vinculin, a molecular marker of costameres in skeletal muscle myofibers. Co-localization is lost in inactive myotubes adopting a diffuse pattern, suggesting that the costameric organization is disrupted in TTX-treated myotubes. Moreover, the inhibition of spontaneous electrical activity decreases myotube cell adhesion. In summary, this work shows that syndecan-4 and beta1 integrin protein levels and their localization in costameric structures are regulated by electrical activity and suggests that this regulatory mechanism influences the adhesion properties of skeletal myotubes during differentiation. PMID- 20362054 TI - Age-dependent changes in the structure, composition and biophysical properties of a human basement membrane. AB - Basement membranes (BMs) are considered to be uniform, approximately 100 nm-thin extracellular matrix sheets that serve as a substrate for epithelial cells, endothelial cells and myotubes. To find out whether BMs maintain their ultrastructure, protein composition and biophysical properties throughout life the natural aging history of the human inner limiting membranes (ILM) was investigated. The ILM is a BM at the vitreal surface of the retina that connects the retina with the vitreous. Transmission electron microscopy (TEM) showed that the ILM steadily increases in thickness from 70 nm at fetal stages to several microns at age 90. By the age of 20, the ILM loses its laminated structure to become an amorphous and very irregular extracellular matrix layer. Atomic force microscopy (AFM) showed that the native, hydrated ILMs are on average 4-fold thicker than the dehydrated ILMs as seen by TEM and that their thickness is prominently determined by its water-binding proteoglycans. The morphological changes are accompanied by age-related changes in the biochemical composition, whereby the relative concentrations of collagen IV and agrin increase, and the concentration of laminin decreases with age. Force-indentation measurements by AFM also showed that ILMs become increasingly stiffer with advancing age. The data suggest that BMs from other human tissues may undergo similar age-related changes. PMID- 20362055 TI - Sex steroid metabolism in the regulation of bone health in men. AB - The growth and maintenance of both the female and the male skeleton are influenced by sex steroids. Although the regulation of the female skeleton by estrogens is well established, the relative importance of androgens and estrogens for the male skeleton remains uncertain. Evidence from cross-sectional and longitudinal studies suggests that serum estradiol levels are more strongly associated with bone mineral density, bone turnover and bone loss than testosterone levels are in adult men. In addition, it appears that a threshold level of serum estradiol exists for optimal skeletal maturation and prevention of both bone loss and fractures. Also, the specificity of the assay technique should be considered when examining serum sex steroid levels in epidemiological cohorts, with a preference for the gold standard mass spectrometry. Additionally, serum levels of sex steroid metabolites, rather than the bio-active sex steroids, may be better markers of local sex steroid action at the target tissue level. In this respect, serum levels of glucuronidated androgen metabolites appear to provide additional information as markers of local androgenic activity in bone than the bio-active androgens. Taken together, even though an important role of testosterone is not excluded, estradiol is an important regulator of bone health in men. PMID- 20362056 TI - Cholesterol 7alpha-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat. AB - Depleted uranium (DU) is a radioactive heavy metal derived from the nuclear energy production. Its wide use in civilian and military items increases the risk of its environmental dissemination, and thus the risk of internal contamination of populations living in such contaminated territories. Previous studies have shown that vitamin D and cerebral cholesterol metabolisms were affected following chronic ingestion of DU. Even more than the brain, the liver is a crucial organ in cholesterol homeostasis since it regulates cholesterol distribution and elimination at body level. The aim of this work was to assess the impact of a low level chronic ingestion of DU on hepatic cholesterol metabolism. Rats were contaminated with DU in their drinking water at a concentration of 40mg/l for 9 months. The major effect induced by DU was a decrease of CYP7A1 specific activity (-60%) correlated with a matching decrease of its product 7alpha hydroxycholesterol in the plasma. Hepatic gene expression of transporters ABC A1, ABC G5, ABC G8 and of nuclear receptor RXR was increased, whereas that of catabolism enzyme CYP7B1 was decreased. Thus, after a chronic ingestion of DU, rats experience a modulation of cholesterol catabolism but overcome it, since their cholesterolemia is preserved and no pathology is declared. PMID- 20362057 TI - The Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) voltage-gated sodium channel and mutations associated with pyrethroid resistance in field-collected adult males. AB - Helicoverpa zea is one of the most costly insect pests of food and fiber crops throughout the Americas. Pyrethroid insecticides are widely applied for its control as they are effective and relatively inexpensive; however, resistance to pyrethroids threatens agricultural systems sustainability because alternative insecticides are often more expensive or less effective. Although pyrethroid resistance has been identified in this pest since 1990, the mechanisms of resistance have not yet been elucidated at the molecular level. Pyrethroids exert their toxicity by prolonging the open state of the voltage-gated sodium channel. Here we report the cDNA sequence of the H. zea sodium channel alpha-subunit homologous to the para gene from Drosophila melanogaster. In field-collected males which were resistant to cypermethrin as determined by the adult vial test, we identify known resistance-conferring mutations L1029H and V421M, along with two novel mutations at the V421 residue, V421A and V421G. An additional mutation, I951V, may be the first example of a pyrethroid resistance mutation caused by RNA editing. Identification of the sodium channel cDNA sequence will allow for testing hypotheses on target-site resistance for insecticides acting on this channel through modeling and expression studies. Understanding the mechanisms responsible for resistance will greatly improve our ability to identify and predict resistance, as well as preserve susceptibility to pyrethroid insecticides. PMID- 20362058 TI - Expression and purification of secreted recombinant hsp60 from eukaryotic cells. AB - Human heat shock protein 60 (hsp60) is a mitochondrial protein that functions as a molecular chaperone. Recently, it has been observed that hsp60 can become exposed on the cell surface and released into the extracellular space. Extracellular hsp60 is thought to function as a danger signal that activates the immune response. However, concerns have been raised that the effects of recombinant hsp60 on cytokines might be the result of contamination with bacterial components, given that the recombinant hsp60 protein used in these studies was produced with a bacterial expression system. In the present study, recombinant hsp60 was produced using a eukaryotic expression system, and the resulting protein was purified. The results obtained demonstrated that recombinant hsp60 was secreted efficiently from cells when fused to the leader peptide of interleukin-2 and the secreted protein was modified by N-linked glycosylation. Furthermore, we successfully obtained unglycosylated recombinant protein that was capable of binding to macrophages. PMID- 20362059 TI - A clustering approach to multireference alignment of single-particle projections in electron microscopy. AB - Two-dimensional analysis of projections of single-particles acquired by an electron microscope is a useful tool to help identifying the different kinds of projections present in a dataset and their different projection directions. Such analysis is also useful to distinguish between different kinds of particles or different particle conformations. In this paper we introduce a new algorithm for performing two-dimensional multireference alignment and classification that is based on a Hierarchical clustering approach using correntropy (instead of the more traditional correlation) and a modified criterion for the definition of the clusters specially suited for cases in which the Signal-to-Noise Ratio of the differences between classes is low. We show that our algorithm offers an improved sensitivity over current methods in use for distinguishing between different projection orientations and different particle conformations. This algorithm is publicly available through the software package Xmipp. PMID- 20362060 TI - Two cysteine proteinases respond to bacterial and WSSV challenge in Chinese white shrimp Fenneropenaeus chinensis. AB - The cDNAs encoding CathL and legumain from Chinese white shrimp Fenneropenaeus chinensis (FcCathL, FcLegu) were obtained. Both FcCathL and FcLegu mRNA were expressed mainly in the hepatopancreas of unchallenged shrimp. Time-course analysis of FcCathL showed that FcCathL was upregulated in the hepatopancreas of shrimp challenged with white spot syndrome virus (WSSV) at 12 h. FcLegu mRNA in hepatopancreas was down-regulated by Vibrio. FcLegu transcript first declined from 2 h to 6 h and then recovered from 12 h to 24 h in hepatopancreas challenged with WSSV. FcCathL protein was detected in the hemocytes, hepatopancreas, gill, stomach, and intestine of unchallenged shrimp. Three bands of FcCathL protein detected in some tissues may represent preproenzyme, single chain and mature double chain form respectively. In hepatopancreas, FcLegu was detected in the proenzyme form. In other tissues, only active form could be detected. The protein of FcLegu was down-regulated by Vibrio or WSSV challenge in the stomach and gills. FcCathL and FcLegu were proposed to play a role in shrimp innate immunity for the first time. PMID- 20362061 TI - Patient-specific analysis of the relationship between the volume of tissue activated during DBS and verbal fluency. AB - Deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease involves implantation of a lead with four small contacts usually within the subthalamic nucleus (STN) or globus pallidus internus (GPi). While generally safe from a cognitive standpoint, STN DBS has been commonly associated with a decrease in the speeded production of words, a skill referred to as verbal fluency. Virtually all studies comparing presurgical to postsurgical verbal fluency performance have detected a decrease with DBS. The decline may be attributable in part to the surgical procedures, yet the relative contributions of stimulation effects are not known. In the present study, we used patient-specific DBS computer models to investigate the effects of stimulation on verbal fluency performance. Specifically, we investigated relationships of the volume and locus of activated STN tissue to verbal fluency outcome. Stimulation of different electrode contacts within the STN did not affect total verbal fluency scores. However, models of activation revealed subtle relationships between the locus and volume of activated tissue and verbal fluency performance. At ventral contacts, more tissue activation inside the STN was associated with decreased letter fluency performance. At optimal contacts, more tissue activation within the STN was associated with improved letter fluency performance. These findings suggest subtle effects of stimulation on verbal fluency performance, consistent with the functional nonmotor subregions/somatotopy of the STN. PMID- 20362062 TI - Dynamic brightness induction in V1: analyzing simulated and empirically acquired fMRI data in a "common brain space" framework. AB - Computational neuromodeling may help to further our understanding of how empirical neuroimaging findings are generated by underlying neural mechanisms. Here, we used a simple computational model that simulates early visual processing of brightness changes in a dynamic, illusory display. The model accurately predicted illusory brightness changes in a grey area of constant luminance induced by (and in anti-phase to) luminance changes in its surroundings. Moreover, we were able to directly compare these predictions with recently observed fMRI results on the same brightness illusion by projecting predicted activity from our model onto empirically investigated brain regions. This new approach in which generated network activity and measured neuroimaging data are interfaced in a common representational "brain space" can contribute to the integration of computational and experimental neuroscience. PMID- 20362063 TI - Are rapids a barrier for floodplain fishes of the Amazon basin? A demographic study of the keystone floodplain species Colossomamacropomum (Teleostei: Characiformes). AB - We investigated demographic history and population structuring of Colossoma macropomum sampled from 14 localities in the Amazon basin and the Bolivian sub basin; the two basins are separated by a series of 16 rapids. Although genetically differentiated, IMa analyses suggest non-zero bi-directional migration rates, and inter-basin divergence of approximately 17 thousand years ago. Analyses in BEAST indicated that Bolivian C. macropomum has been demographically stable except for a moderate population increase in the last 12 thousand years, while Amazonian C. macropomum has been experiencing demographic growth over the last 350 thousand years, resulting in approximately one order of magnitude increase in coalescent N(e). PMID- 20362064 TI - Placement of Conopidae (Diptera) within Schizophora based on mtDNA and nrDNA gene regions. AB - The first attempt to phylogenetically place Conopidae using molecular characters, as well as the largest molecular analysis of relationships within Schizophora (Diptera) to date, is presented. Twenty-eight taxa from 11 acalyptrate families and seven acalyptrate superfamilies are represented. Nearly 12,800 bp of sequence data from 10 genes representing both mitochondrial (cytochrome oxidase I (COI), cytochrome b (cytB), and 12S) and nuclear genes (28S, the carbamoyl phosphate synthetase region of CAD (CAD), elongation factor-1alpha (EF-1alpha), white, alanyl-tRNA synthetase (AATS), triose phosphate isomerase (TPI), and phosphogluconate dehydrogenase (PGD)) are analysed. Parsimony and Bayesian analyses strongly support the monophyly of both Conopidae and Schizophora. While in the parsimony analysis, Conopidae are placed as sister to the remaining Schizophora, the Bayesian analysis recovers a Conopidae+Lauxaniidae clade. The value of nuclear, mitochondrial, ribosomal, and protein-coding gene sequence data for answering phylogenetic questions at different levels of divergence is evaluated. PMID- 20362065 TI - Refractoriness of urethral striated muscle contractility to nitric oxide dependent cyclic GMP production. AB - The purpose of this study was to investigate the role of cyclic GMP (cGMP) in the effects of nitric oxide (NO) on urethral striated muscle and its involvement in contractile function. The localization of cGMP, neuronal NO synthase (nNOS), vimentin, and neuronal markers was assessed by immunofluorescence in the sheep and rat urethra and the expression of nNOS was determined in Western blots. Nerve mediated contractile responses to electrical field stimulation (EFS) were recorded in the sheep urethra. The scant nitrergic innervation of the striated muscle layer suggests that autonomic control of its activity is unlikely. The striated fiber itself may be the source of high levels NO produced by sarcolemmal and/or cytosolic mu or alpha variant of nNOS. This endogenous NO may provoke high basal production of soluble guanylate cyclase (GC) dependent cGMP, mainly in non NO producing muscle fibers, which is not further enhanced by NO donors. cGMP co localizes with neurofilament and PGP 9.5 at muscle endplates. Modulators of the cGMP pathway did not affect nerve-mediated contractile activity induced by EFS, suggesting that cGMP is not a significant mediator of neuromuscular transmission. In addition, NO donors did increase the accumulation of cGMP in dense networks of vimentin immunoreactive interstitial cells of Cajal (ICC), whose function is not yet known. These data suggest that there is a strong but non-regulated production of cGMP under resting conditions, which does not seem to affect contractile function. Modulation of cholinergic neurotransmission by NO through cGMP independent mechanisms cannot be discarded. PMID- 20362066 TI - Expression of prostaglandin synthases (pgds and pges) during zebrafish gonadal differentiation. AB - The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E2 synthase (pges) and especially the lipocalin-type prostaglandin D2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found in other species. In mice and chicken, the lipocalin-type Pgds is specifically expressed in pre Sertoli cells just after Sry and Sox9 and is involved in masculinisation of the developing testis. Furthermore, Pges are implicated in female reproduction including follicular development and ovulation. In this study, a sexually dimorphic expression of pgds was found in gonads of adult zebrafish with expression in testis but not in ovaries. To determine whether the sex-specific expression pattern of pgds was present in gonads of juvenile zebrafish and therefore could be an early marker of sex in zebrafish, we microdissected gonads from four randomly selected individual zebrafish for every second day in the period 2-20 days post hatch (dph) and 0-1 dph. The temporal expression of pgds and pges was investigated in the microdissected gonads, however, no differential expression that could indicate sex-specific difference between individual juvenile zebrafish was observed. PMID- 20362068 TI - The molecular basis of human retinal and vitreoretinal diseases. AB - During the last two to three decades, a large body of work has revealed the molecular basis of many human disorders, including retinal and vitreoretinal degenerations and dysfunctions. Although belonging to the group of orphan diseases, they affect probably more than two million people worldwide. Most excitingly, treatment of a particular form of congenital retinal degeneration is now possible. A major advantage for treatment is the unique structure and accessibility of the eye and its different components, including the vitreous and retina. Knowledge of the many different eye diseases affecting retinal structure and function (night and colour blindness, retinitis pigmentosa, cone and cone rod dystrophies, photoreceptor dysfunctions, as well as vitreoretinal traits) is critical for future therapeutic development. We have attempted to present a comprehensive picture of these disorders, including biological, clinical, genetic and molecular information. The structural organization of the review leads the reader through non-syndromic and syndromic forms of (i) rod dominated diseases, (ii) cone dominated diseases, (iii) generalized retinal degenerations and (iv) vitreoretinal disorders, caused by mutations in more than 165 genes. Clinical variability and genetic heterogeneity have an important impact on genetic testing and counselling of affected families. As phenotypes do not always correlate with the respective genotypes, it is of utmost importance that clinicians, geneticists, counsellors, diagnostic laboratories and basic researchers understand the relationships between phenotypic manifestations and specific genes, as well as mutations and pathophysiologic mechanisms. We discuss future perspectives. PMID- 20362067 TI - Complexity of retinal cone bipolar cells. AB - An open issue of retinal organization and function is the comprehension of the different tasks specifically performed by bipolar cells, the neurons that collect information from photoreceptors in the outer retina and convey the signal to the inner plexiform layer. Particularly interesting is to understand the unique contribution to the visual signal brought by cone bipolar cells, neurons typical of the mammalian retina and especially dedicated to receive synaptic input from cones. In all the species studied so far, it has been shown that cone bipolar cells occur in about ten different types, which form distinct clusters identified with a panel of both classical and modern genetic methods. Reviewed here is current literature illustrating the occurrence of morphological, molecular and architectural features that confer to each bipolar cell type exclusive fingerprints, ultimately predicting the emergence of similarly unique, albeit still partially unraveled, functional properties. Thus, differences among cone bipolar cells lay the ground for the genesis in the outer retina of parallel channels, which convey to the inner retina separate information, among others, about contrast, chromatic features and temporal properties of the visual signal. PMID- 20362069 TI - Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells. AB - Stromal derived factor-1 (SDF-1) is a chemokine signaling molecule that binds to its transmembrane receptor CXC chemokine receptor-4 (CXCR4). While we previously detected that SDF-1 was co-required with bone morphogenetic protein 2 (BMP2) for differentiating mesenchymal C2C12 cells into osteoblastic cells, it is unknown whether SDF-1 is similarly involved in the osteogenic differentiation of mesenchymal stem cells (MSCs). Therefore, here we examined the role of SDF-1 signaling during BMP2-induced osteogenic differentiation of primary MSCs that were derived from human and mouse bone marrow. Our data showed that blocking of the SDF-1/CXCR4 signal axis or adding SDF-1 protein to MSCs significantly affected BMP2-induced alkaline phosphatase (ALP) activity and osteocalcin (OCN) synthesis, markers of preosteoblasts and mature osteoblasts, respectively. Moreover, disrupting the SDF-1 signaling impaired bone nodule mineralization during terminal differentiation of MSCs. Furthermore, we detected that blocking of the SDF-1 signaling inhibited the BMP2-induced early expression of Runt related factor-2 (Runx2) and osterix (Osx), two "master" regulators of osteogenesis, and the SDF-1 effect was mediated via intracellular Smad and Erk activation. In conclusion, our results demonstrated a regulatory role of SDF-1 in BMP2-induced osteogenic differentiation of MSCs, as perturbing the SDF-1 signaling affected the differentiation of MSCs towards osteoblastic cells in response to BMP2 stimulation. These data provide novel insights into molecular mechanisms underlying MSC osteogenesis, and will contribute to the development of MSC therapies for enhancing bone formation and regeneration in broad orthopaedic situations. PMID- 20362070 TI - Comparison of different cytotoxicity measures for the in vitro micronucleus test (MNVit) in L5178Y tk(+/-) cells: Summary of 4 compounds (Mitomycin C, Cyclophosphamide, Colchicine and Diethylstilboestrol) with clastogenic and aneugenic mode of action. AB - This study summarises the results of four different chemicals evaluated for induction of micronuclei (MN) in L5178Y tk(+/-) cells in the absence of cytochalasin B. All four chemicals (the tubulin polymerisation inhibitor Colchicine, Diethylstilboestrol which inhibits both tubulin polymersation as well as depolymerisation, the cross-linking agent Mitomycin C and Cyclophosphamide which requires metabolism to form the ultimate mutagen) showed biologically and statistically significant induction in MN frequency compared to concurrent controls. Irrespective of whether the measure of cytotoxicity was based on relative cell count (RCC), relative increase in cell count (RICC) or relative population doubling (RPD), micronucleus induction was observed at or below the targeted toxicity of 55+/-5%. Therefore, all measures of cytotoxicity in the absence of cytochalasin B proved to be equally acceptable to select the top-dose without missing micronucleation activity for any of the four compounds. PMID- 20362071 TI - Selecting information in electronic health records for knowledge acquisition. AB - Knowledge acquisition of relations between biomedical entities is critical for many automated biomedical applications, including pharmacovigilance and decision support. Automated acquisition of statistical associations from biomedical and clinical documents has shown some promise. However, acquisition of clinically meaningful relations (i.e. specific associations) remains challenging because textual information is noisy and co-occurrence does not typically determine specific relations. In this work, we focus on acquisition of two types of relations from clinical reports: disease-manifestation related symptom (MRS) and drug-adverse drug event (ADE), and explore the use of filtering by sections of the reports to improve performance. Evaluation indicated that applying the filters improved recall (disease-MRS: from 0.85 to 0.90; drug-ADE: from 0.43 to 0.75) and precision (disease-MRS: from 0.82 to 0.92; drug-ADE: from 0.16 to 0.31). This preliminary study demonstrates that selecting information in narrative electronic reports based on the sections improves the detection of disease-MRS and drug-ADE types of relations. Further investigation of complementary methods, such as more sophisticated statistical methods, more complex temporal models and use of information from other knowledge sources, is needed. PMID- 20362072 TI - Background adjustment of cDNA microarray images by Maximum Entropy distributions. AB - Many empirical studies have demonstrated the exquisite sensitivity of both traditional and novel statistical and machine intelligence algorithms to the method of background adjustment used to analyze microarray datasets. In this paper we develop a statistical framework that approaches background adjustment as a classic stochastic inverse problem, whose noise characteristics are given in terms of Maximum Entropy distributions. We derive analytic closed form approximations to the combined problem of estimating the magnitude of the background in microarray images and adjusting for its presence. The proposed method reduces standardized measures of log expression variability across replicates in situations of known differential and non-differential gene expression without increasing the bias. Additionally, it results in computationally efficient procedures for estimation and learning based on sufficient statistics and can filter out spot measures with intensities that are numerically close to the background level resulting in a noise reduction of about 7%. PMID- 20362074 TI - Letter to the Editor--SVT with delayed atrial depolarization after His synchronous ventricular stimulation. PMID- 20362073 TI - Perinatal changes in superoxide generation in the ovine lung: Alterations associated with increased pulmonary blood flow. AB - Although alterations in ROS generating systems are well described in several vascular disorders, there is very limited information on the perinatal regulation of these systems in the lung both during normal development and in pulmonary hypertension. Thus, this study was undertaken to explore how the two predominant superoxide generating systems, nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and xanthine oxidase (XO), are developmentally regulated in control lambs and in our established lamb model of increased pulmonary blood flow (Shunt) over the first 2months of life. We found that the levels of p47(phox), p67(phox), and Rac1 subunits of NADPH oxidase complex were altered. During the first two months of life there was no change in p47(phox) protein levels in either normal or Shunt lambs. However, both p67(phox) and Rac1 protein levels decreased over time. In addition, p47(phox) protein levels were significantly increased in shunt lambs at 2- and 4-, but not 8-weeks of age compared to age-matched controls while levels of the p67(phox) subunit were decreased at 8-weeks of age in the Shunts but unchanged at other time periods. Furthermore, Rac1 protein expression was significantly increased in the Shunts only at 4weeks of age. These data correlated with a significant increase in NADPH oxidase dependent superoxide generation at 2- and 4-, but not 8-weeks of age in the Shunts. During normal development XO levels significantly increased over time in normal lambs but significantly decreased in the Shunts. In addition, XO protein levels were significantly increased in the Shunt at 2- and 4-weeks of age but significantly decreased at 8-weeks. Again this correlated with a significant increase in XO dependent superoxide generation at 2- and 4-, but not 8-weeks of age in the Shunts. Collectively, our findings suggest that NADPH oxidase and XO are major contributors to superoxide generation both during the normal development and during the development of pulmonary hypertension. PMID- 20362076 TI - First case of multidrug-resistant tuberculosis caused by a rare "Beijing-like" genotype of Mycobacterium tuberculosis in Bogota, Colombia. AB - This report describes a first case due to a genetically distinct and relatively rare "Beijing-like" strain of Mycobacterium tuberculosis isolated from a 15 years old female patient who died shortly after the initiation of antituberculous therapy with second-line drugs. Positive cultures obtained from lung, kidney and adrenal glands upon autopsy were identified as Mycobacterium tuberculosis complex characterized by an identical 15-banded IS6110-RFLP pattern, and were found to be resistant to all the 4 first-line antituberculous drugs tested (rifampin, isoniazid, ethambutol and streptomycin). Spoligotyping followed by comparison with the SITVIT2 database revealed that the isolate belonged to a rare pattern identified as Spoligotype International Type SIT190, which represents only 1.7% of all the Beijing strains worldwide. We present data on its worldwide distribution and present an evolutionary scenario based on available MIRU typing data. PMID- 20362077 TI - Serum M30 levels are associated with survival in advanced gastric carcinoma patients. AB - BACKGROUND: Cytokeratin 18 (CK-18) is a cytoskeleton protein of epithelial cells which are released into the circulation during necrotic or apoptotic cell death. M30 detects caspase-cleaved neo-epitope of CK-18; whereas M 65 measures whole length intact protein. We aimed to evaluate the prognostic significance of serum M65 and M30 levels in patients with gastric carcinoma. METHODS: Thirty eight patients with advanced disease were included in the study. Thirty-two healthy people were chosen as control group. Serum M65 and M30 levels were measured by quantitative ELISA method. RESULTS: Serum M65 levels were found significantly elevated in patients compared to control group (385.7+/-280.6 vs. 200.2+/-164.5, p=0.002). Serum M30 levels were significantly increased in patients compared to the control group (204.6+/-245 vs. 106.5+/-17.5, p=0.03). Patients with metastatic disease had significantly higher levels of serum M30 compared to patients with locally advanced disease (267.1+/-296.1 vs. 102.3+/-53.2, p=0.03). Serum M30 and M65 levels were evaluated in respect to survival. Best cut-off value for the prediction of death for M30 antigen level was 83.8U/L. Patients with higher M30 levels had significantly shorter median survival compared to patients' lower serum M30 levels. However, there was no impact of serum M65 levels on survival. Serum M30 levels and clinical stage were found as the strongest variables with independent prognostic value for overall survival. DISCUSSION: These results suggest that serum M65 and M30 levels were elevated in patients with advanced gastric carcinoma patients. Serum M30 levels can be helpful to predict tumor load and also survival. PMID- 20362078 TI - Regulation of telomerase activity by apparently opposing elements. AB - Telomeres, the ends of chromosomes, undergo frequent remodeling events that are important in cell development, proliferation and differentiation, and neoplastic immortalization. It is not known how the cellular environment influences telomere remodeling, stability, and lengthening or shortening. Telomerase is a ribonucleoprotein complex that maintains and lengthens telomeres in the majority of cancers. Recent studies indicate that a number of factors, including hormones, cytokines, ligands of nuclear receptor, vitamins and herbal extracts have significantly influence telomerase activity and, in some instances, the remodeling of telomeres. This review summarizes the advances in understanding of the positive and negative regulation by extracellular factors of telomerase activity in cancer, stem cells and other systems in mammals. PMID- 20362079 TI - Telmisartan alleviates rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats. AB - In the present study, we systematically examined telmisartan, an angiotensin AT(1) receptor antagonist, on rosiglitazone-induced bone loss in ovariectomized spontaneously hypertensive rats. Telmisartan (5 mg/kg/d, 90 days) was found to be able to significantly alleviate rosiglitazone (10 mg/kg/d, 90 days)-induced decrease in BMD of femur and lumbar vertebrae. The BMD changes were associated with positive biomechanical changes of lumbar vertebrae, improvements in microarchitecture of tibial metaphysic and normalized serum osteocalcin (OC) levels and urinary deoxypyridinoline/creatinine (DPD/Cr) ratio. MicroCT analysis of the tibial metaphysis showed that telmisartan significantly prevented the decreases in bone volume/tissue volume (BV/TV), connect density (Conn. D.), trabecular number (Tb. N.) and trabecular thickness (Tb. Th.), and increase in trabecular separation (Tb. Sp.) induced by rosiglitazone. Histomorphometric analysis also showed that telmisartan had protective effects on rosiglitazone reduced bone formation indices such as histomorphometric bone volume fraction (BV/TV-Histo), mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR/BS). Our study clearly showed that telmisartan alleviated rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats. The relief of bone loss provides a possible therapeutic application of telmisartan with rosiglitazone for the treatment of elderly women patients afflicted with metabolic syndrome. PMID- 20362080 TI - Circulating osteogenic cells: characterization and relationship to rates of bone loss in postmenopausal women. AB - There is increasing evidence that osteogenic cells are present not only in bone marrow (BM) but also in peripheral blood (PB). Since staining for alkaline phosphatase (AP) identifies osteoprogenitor cells in BM, we sought to further characterize BM versus PB hematopoietic lineage negative (lin-)/AP+ cells and to compare gene expression in PB lin-/AP+ cells from postmenopausal women undergoing rapid versus slow bone loss. PB lin-/AP+ cells were smaller than their BM counterparts, and both were negative for the pan-hematopoietic marker, CD45. BM and PB lin-/AP+ cells were capable of mineralization in vitro. Using whole genome linear amplification followed by quantitative polymerase chain reaction (QPCR) analysis, we found that relative to the BM cells, PB lin-/AP+ cells expressed similar levels of a number of key osteoblast marker genes (runx2, osterix, osteopontin, OPG, periostin), consistent with the PB cells being in the osteoblastic lineage. Importantly, however, compared to the BM cells, PB lin-/AP+ cells expressed lower levels of mRNAs for AP, type I collagen, and for a panel of proliferation markers, but higher levels of osteocalcin, osteonectin, and PTHR1 mRNAs, as well as those for RANKL and ICAM-1, both of which are important in supporting osteoclastogenesis. Using microarray followed by QPCR analysis, we further demonstrated that, compared to postmenopausal women undergoing slow bone loss, PB lin-/AP+ cells from women undergoing rapid bone loss expressed lower levels of mRNAs for hydroxyprostaglandin dehydrogenase, interferon regulator factor 3, Wnt1-induced secreted protein 1, and TGFbeta2, but higher levels of the Smad3 interacting protein, zinc finger DHHC-type containing 4 and col1alpha2. These data thus demonstrate that while PB lin-/AP+ cells express a number of osteoblastic genes and are capable of mineralization, they are a relatively quiescent cell population, both in terms of cell proliferation and matrix synthesis. However, their higher expression of RANKL and ICAM-1 mRNAs as compared to BM lin-/AP+ cells suggests a role for the PB lin-/AP+ cells in regulating osteoclastogenesis that warrants further investigation. Our study also provides "proof-of-concept" for the use of PB lin-/AP+ cells in clinical-investigative studies, and identifies several pathways that could potentially regulate rates of bone loss in postmenopausal women. PMID- 20362081 TI - Prevalence and risk factors of osteoporosis in Korea: a community-based cohort study with lumbar spine and hip bone mineral density. AB - PURPOSE: To investigate bone mineral density (BMD) profiles, osteoporosis prevalence and risk factors in a community-based cohort in Korea. METHODS: The present study is a cross-sectional study. The study population consisted of 1,547 men and 1991 women aged 40 years and older with BMD measurements using central dual energy X-ray absorptiometry from a prospective community-based cohort. The data were compared with other ethnic groups. Risk factors related to osteoporosis were analyzed. RESULTS: Crude prevalence of osteoporosis in the whole subjects (40-79 years old) was 13.1% for men and 24.3% for women by WHO criteria, at any site among lumbar spine, femoral neck or total hip. Standardized prevalence of osteoporosis between age of 50 and 79 at lumbar spine, femoral neck and total hip was 12.9%, 1.3% and 0.7% in men and 24.0%, 5.7% and 5.6% in women, respectively. The mean BMD of studied female subjects after age of 50 was not significantly different from that of Chinese but significantly lower than that of Japanese, non Hispanic whites, non-Hispanic blacks and Mexican Americans. Risk of osteoporosis was significantly associated with the presence of past fracture history (OR, 1.45; 95% CI, 1.08-1.94), smoking> or =1 pack/day (OR, 1.63; 95% CI, 1.01-2.62), menarche after age of 16 (OR, 1.46; 95% CI, 1.14-1.87), last delivery after age of 30 (OR, 1.58; 95% CI, 1.20-2.09), more than three offspring (OR, 1.42; 95% CI, 1.07-1.89), post-menopause status (OR, 7.32; 95% CI, 3.05-17.6), more than 17 years since menopause (OR, 1.53; 95% CI, 1.10-2.14), regular exercise of two to three times per week (OR, 0.40; 95% CI, 0.18-0.89), monthly income above 500,000 won per household (OR, 0.64; 95% CI, 0.45-0.92), college graduate (OR, 0.29; 95% CI, 0.13-0.63) and calcium intake> or =627.5 mg/day (OR, 0.65; 95% CI, 0.43-0.98) after adjusting for age and BMI. CONCLUSION: The BMD and osteoporosis prevalence of Koreans are presented. Risk of osteoporosis was significantly associated with fracture history, smoking, reproductive history, regular exercise, income level, education background and calcium intake. PMID- 20362083 TI - From central to rudimentary to primary: the history of an underappreciated organelle whose time has come. The primary cilium. AB - For the first time, the history of the central flagellum/primary cilium has been explored systematically and in depth. It is a long and informative story about the course of scientific discovery, memory loss and rediscovery. The progress of our story is saltatory, pushed onward by innovations in technology and retarded by socio-scientific issues of linguistic and temporal chauvinism. Over one hundred and fifty years passed between the discovery of this organelle and full appreciation of its important functions. The main character in our story is an organelle that was relegated to a very minor role in the cellular opera for a very long time, until its rather sudden promotion to a central role in orchestrating many of the sensory and signaling events of the cell. Although early investigators speculated on just such a role for the primary cilium as early as 1898, it was over one hundred years before proof for this hypothesis was forthcoming. PMID- 20362084 TI - Origin of the cilium: novel approaches to examine a centriolar evolution hypothesis. AB - Recently, a new hypothesis was proposed regarding the evolution of the cilium from an enveloped RNA virus (Satir et al., 2007, Cell Motil. Cytoskeleton 64, 906). The hypothesis predicts that there may be specific centriolar or basal body RNAs with sequences reminiscent of retroviruses, and/or that the nuclear genes for certain centriole-specific proteins would have viral origins. Four independent laboratories have reported the existence of centrosomal RNA (cnRNA). Methods for studying cnRNA are described. We analyzed evidence of relatedness of known full-length cnRNAs to extant viral molecules. Out of 14 cnRNAs studied, 12 have similarity to entries in viral databases, all but one of these with E-values of < or = 1e(-4). Some centrosomal, and possibly uniquely centriolar, proteins also have relatives in viral databases that meet the criteria accepted to indicate a relationship by descent. Nine general cytoskeleton proteins exhibited no significant similarity to viral proteins. The speculation that centrioles are invaders of RNA viral origin in the evolving eukaryotic cell is strengthened by these findings. PMID- 20362085 TI - Using quantitative PCR to identify kinesin-3 genes that are upregulated during growth arrest in mouse NIH3T3 cells. AB - Most cells in our body form a single primary cilium when entering growth arrest. During the past decade, a number of studies have revealed a key role for primary cilia in coordinating a variety of signaling pathways that control important cellular and developmental processes. Consequently, significant effort has been directed toward the identification of genes involved in ciliary assembly and function. Many candidate ciliary genes and proteins have been identified using large-scale "omics" approaches, including proteomics, transcriptomics, and comparative genomics. Although such large-scale approaches can be extremely informative, additional validation of candidate ciliary genes using alternative "small-scale" approaches is often necessary. Here we describe a quantitative PCR based method that can be used to screen groups of genes for those that are upregulated during growth arrest in cultured mouse NIH3T3 cells and those that might have cilia-related functions. We employed this method to specifically search for mouse kinesin-3 genes that are upregulated during growth arrest and identified three such genes (Kif13A, Kif13B, and Kif16A). In principle, however, the method can be extended to identify other genes or gene families that are upregulated during growth arrest. PMID- 20362086 TI - Methods for the isolation of sensory and primary cilia--an overview. AB - Detailed proteomic analyses of mammalian olfactory and rod photoreceptor sensory cilia are now available, providing an inventory of resident ciliary proteins and laying the foundation for future studies of developmental and spatiotemporal changes in the composition of sensory cilia. Cilia purification methods that were elaborated and perfected over several decades were essential for these advances. In contrast, the proteome of primary cilia is yet to be established, because purification procedures for this organelle have been developed only recently. In this chapter, we review current techniques for the purification of olfactory and photoreceptor cilia, and evaluate methods designed for the selective isolation of primary cilia. PMID- 20362087 TI - Isolation of primary cilia for morphological analysis. AB - Primary cilia are present in most mammalian cells and have lately been recognized as important cellular sensors that integrate and transduce extracellular signals into functional responses. Development of approaches to isolate primary cilia of sufficient quantity and quality for biochemical and molecular studies are crucial to understand their roles and functions under normal and pathological conditions. Two separate but complementary techniques (i.e., peel-off and slide pulling) to isolate enriched ciliary fractions from cultured epithelial cells are described. The purity and quantity of isolated cilia is verified by immunofluorescent confocal microscopy, light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), and western blot analysis. Examples of detection of ciliary-associated proteins using isolated cilia are shown. These techniques will allow the isolation of primary cilia from cultured epithelial cells and permit further examination of the expression and localization of proteins of interest, helping to elucidate the role of primary cilia in health and disease. PMID- 20362088 TI - Analyzing primary cilia by multiphoton microscopy. AB - In this chapter, a technique is outlined for the use of immunohistochemistry (IHC) followed by multiphoton microscopy (MPM) for the analysis of incidence, length, and 3D orientation of the axoneme of the primary cilium. Although the application presented specifically emphasizes localizations in tenocytes and chondrocytes, the technique is applicable to cells in a wide range of connective tissues. The primary advantages of utilizing MPM as opposed to TEM for these kinds of ciliary analyses are the rapidity of the technique for preparation of the samples and the ability to collect data from multiple cells simultaneously. Using MPM, the axoneme, basal body, and associated centriole can be visualized by specific IHC with localizing antibodies. However, the resolution achieved through TEM analyses allows the complex morphology of the primary cilium to be visualized, and this remains the primary advantage of TEM versus MPM. SHG, which occurs only with MPM, allows visualization of collagen fibrils and is particularly advantageous for localizing primary cilia associated with cells in connective tissues. This, and the deep penetration with less photobleaching, are the primary advantages of MPM compared to confocal microscopy. As with any microscopical technique, the protocol needs to be optimized for any given tissue. In particular, additional antigen retrieval techniques to enhance the unmasking of specific epitopes for antibody binding may be required for adaptation of this approach to other dense connective tissues with complex spatial organizations such as intervertebral disc or meniscus. PMID- 20362090 TI - Utilization of conditional alleles to study the role of the primary cilium in obesity. AB - Ciliopathies are a group of human diseases that involve dysfunction of the cilium. Human patients with mutations in ciliary proteins can exhibit a wide range of phenotypes, one of which is obesity. This is seen in patients with Bardet-Biedl syndrome (BBS) and Alstrom syndrome (ALMS). Both of these disorders are caused by mutations in proteins that localize to the cilium or the basal body at the base of the cilium. These rare human disorders and their corresponding mouse models together with genetic approaches to disrupt cilia on specific cell types are beginning to uncover the connection between the cilium and energy homeostasis. Here we will review the current data on how cilia are thought to be involved in energy homeostatic pathways and discuss several key factors to consider when utilizing conditional approaches to evaluate ciliary function and their link to obesity. PMID- 20362091 TI - Using nucleofection of siRNA constructs for knockdown of primary cilia in P19.CL6 cancer stem cell differentiation into cardiomyocytes. AB - Primary cilia assemble as solitary organelles in most mammalian cells during growth arrest and are thought to coordinate a series of signal transduction pathways required for cell cycle control, cell migration, and cell differentiation during development and in tissue homeostasis. Recently, primary cilia were suggested to control pluripotency, proliferation, and/or differentiation of stem cells, which may comprise an important source in regenerative biology. We here provide a method using a P19.CL6 embryonic carcinoma (EC) stem cell line to study the function of the primary cilium in early cardiogenesis. By knocking down the formation of the primary cilium by nucleofection of plasmid DNA with siRNA sequences against genes essential in ciliogenesis (IFT88 and IFT20) we block hedgehog (Hh) signaling in P19.CL6 cells as well as the differentiation of the cells into beating cardiomyocytes (Clement et al., 2009). Immunofluorescence microscopy, western blotting, and quantitative PCR analysis were employed to delineate the molecular and cellular events in cilia-dependent cardiogenesis. We optimized the nucleofection procedure to generate strong reduction in the frequency of ciliated cells in the P19.CL6 culture. PMID- 20362089 TI - Primary cilia and the cell cycle. AB - Cilia are microtubule-based structures that protrude from the cell surface and function as sensors for mechanical and chemical environmental cues that regulate cellular differentiation or division. In metazoans, ciliary signaling is important during organismal development and in the homeostasis controls of adult tissues, with receptors for the Hedgehog, platelet derived growth factor (PDGF), Wnt, and other signaling cascades arrayed and active along the ciliary membrane. In normal cells, cilia are dynamically regulated during cell cycle progression: present in G0 and G1 cells, and usually in S/G2 cells, but almost invariably resorbed before mitotic entry, to reappear post-cytokinesis. This periodic resorption and reassembly of cilia, specified by the intrinsic cell cycle the intrinsic cell cycle machinery, influences the susceptibility of cells to the influence of extrinsic signals with cilia-associated receptors. Pathogenic conditions of mammals associated with loss of or defects in ciliary integrity include a number of developmental disorders, cystic syndromes in adults, and some cancers. With the continuing expansion of the list of human diseases associated with ciliary abnormalities, the identification of the cellular mechanisms regulating ciliary growth and disassembly has become a topic of intense research interest. Although these mechanisms are far from being understood, a number of recent studies have begun to identify key regulatory factors that may begin to offer insight into disease pathogenesis and treatment. In this chapter we will discuss the current state of knowledge regarding cell cycle control of ciliary dynamics, and provide general methods that can be applied to investigate cell cycle-dependent ciliary growth and disassembly. PMID- 20362093 TI - Detecting the surface localization and cytoplasmic cleavage of membrane-bound proteins. AB - Polycystin-1 (PC1) is a large, membrane-bound protein that localizes to the cilia and is implicated in the common ciliopathy autosomal-dominant polycystic kidney disease. The physiological function of PC1 is dependent upon its subcellular localization as well as specific cleavages that release soluble fragments of its C-terminal tail. The techniques described here allow visualization and quantification of these aspects of the biology of the PC1 protein. To visualize PC1 at the plasma membrane, a live-cell surface labeling immunofluorescence protocol paired with the labeling of an internal antigen motif allows a robust detection of the surface population of this protein. This technique is modified to generate a surface enzyme-linked immunosorbent assay (ELISA), which quantitatively measures the amount of surface protein as a fraction of the total amount of the protein expressed in that cell population. These assays are powerful tools in the assessment of the small but biologically important pool of PC1 that reaches the cell surface. The C-terminal tail cleavage of PC1 constitutes an interesting modification that allows PC1 to extend its functional role into the nucleus. A reporter assay based on Gal4/VP16 luciferase can be used to quantitate the amount of PC1 C-terminal tail that reaches the nucleus. This assay can be paired with quantitative measurement of the protein expression in the cell, allowing a more complete understanding of the pattern of PC1 cleavage and the nuclear localization of the resultant. PMID- 20362092 TI - The primary cilium as a Hedgehog signal transduction machine. AB - The Hedgehog (Hh) signal transduction pathway is essential for the development and patterning of numerous organ systems, and has important roles in a variety of human cancers. Genetic screens for mouse embryonic patterning mutants first showed a connection between mammalian Hh signaling and intraflagellar transport (IFT), a process required for construction of the primary cilium, a small cellular projection found on most vertebrate cells. Additional genetic and cell biological studies have provided very strong evidence that mammalian Hh signaling depends on the primary cilium. Here, we review the evidence that defines the integral roles that IFT proteins and cilia play in the regulation of the Hh signal transduction pathway in vertebrates. We discuss the mechanisms that control localization of Hh pathway proteins to the cilium, focusing on the transmembrane protein Smoothened (Smo), which moves into the cilium in response to Hh ligand. The phenotypes caused by loss of cilia-associated proteins are complex, which suggests that cilia and IFT play active roles in mediating Hh signaling rather than serving simply as a compartment in which pathway components are concentrated. Hh signaling in Drosophila does not depend on cilia, but there appear to be ancient links between cilia and components of the Hh pathway that may reveal how this fundamental difference between the Drosophila and mammalian Hh pathways arose in evolution. PMID- 20362094 TI - Assay for in vitro budding of ciliary-targeted rhodopsin transport carriers. AB - Primary cilia and cilia-derived sensory organelles are cell's antennas that contain sensory receptors and signal transduction modules. Defects in the expression and targeting of ciliary proteins to this specialized cellular compartment lead to human disorders collectively known as ciliopathies. To examine the molecular basis for the ciliary targeting of the light receptor rhodopsin, we have developed a cell-free assay that reconstitutes its packaging into the specific post-Golgi rhodopsin transport carriers (RTCs). This assay accurately reproduces the in vivo process of carrier budding, while allowing examination of individual components of the macromolecular complexes, thus providing insight into a more general mechanism for the regulation of ciliary membrane targeting. Examples are shown for the use of this assay in rhodopsin trafficking. The cell-free assay is applicable to other ciliary-targeted sensory molecules. PMID- 20362095 TI - Immunoelectron microscopy of vesicle transport to the primary cilium of photoreceptor cells. AB - Cilia are organelles of high structural complexity. Since the biosynthetic machinery is absent from cilia all their molecular components must be synthesized in organelles of the cytoplasm and subsequently transported to the cilium. Ciliary cargos are thought to be translocated in the membrane of transport vesicles or association with these vesicles to the base of the cilium where the vesicles fuse with the periciliary target membrane for further delivery of their cargo into the ciliary compartment by the intraflagellar transport (IFT). Here we describe a modified preembedding labeling method as an alternative technique to conventional postembedding methods eligible for analyses of ciliary cargo vesicles and the distribution of ciliary molecules in subciliary compartments for immunoelectron microscopy. The preembedding labeling method preserves the antigenicity of ciliary antigens and its application reveals differential localization of individual IFT proteins in vertebrate photoreceptor cilia. Since membrane vesicles are conserved, the preembedding protocol additionally allows the identification of ciliary cargo vesicles by immunolabeling of individual IFT proteins and ciliary targeting molecules in ciliary photoreceptor cells. These results do not only confirm the central function of IFT molecules in ciliary transport, but further strengthen their role in transport processes in the cytoplasm. Furthermore, evidence for different alternative transport routes of cargo vesicles directed to different target membranes is gathered. PMID- 20362096 TI - Polycystic kidney disease, cilia, and planar polarity. AB - Cystic kidney diseases are characterized by dilated or cystic kidney tubular segments. Changes in planar cell polarity, flow sensing, and/or proliferation have been proposed to explain these disorders. Over the last few years, several groups have suggested that ciliary dysfunction is a central component of cyst formation. We review evidence for and against each of these models, stressing some of the inconsistencies that should be resolved if an accurate understanding of cyst formation is to be achieved. We also comment on data supporting a model in which ciliary function could play different roles at different developmental stages and on the relevance of dissecting potential differences between pathways required for tubule formation and/or maintenance. PMID- 20362097 TI - Constructing and deconstructing roles for the primary cilium in tissue architecture and cancer. AB - Primary cilia are exquisitely designed sensory machines that have evolved at least three distinct sensory modalities to monitor the extracellular environment. The presence and activation of growth factor, morphogen, and hormone receptors within the confines of the ciliary membrane, the intrinsic physical relationship between the ciliary axoneme and the centriole, and the preferential assembly of primary cilia on the apical surfaces of tissue epithelia highlight the importance of this organelle in the establishment and maintenance of tissue architecture and homeostasis. Accordingly, recent studies begin to suggest roles for these organelles in oncogenesis and tumor suppression. Here, we review the sensory properties of primary cilia, assess the "history" of the primary cilium in cancer, and draw upon recent findings in a discussion of how the primary cilium may influence tissue architecture and neoplasia. PMID- 20362098 TI - Polyglutamylation and the fleer gene. PMID- 20362099 TI - Regulation of cilia assembly, disassembly, and length by protein phosphorylation. AB - The exact mechanism by which cells are able to assemble, regulate, and disassemble cilia or flagella is not yet completely understood. Recent studies in several model systems, including Chlamydomonas, Tetrahymena, Leishmania, Caenorhabditis elegans, and mammals, provide increasing biochemical and genetic evidence that phosphorylation of multiple protein kinases plays a key role in cilia assembly, disassembly, and length regulation. Members of several protein kinase families--including aurora kinases, never in mitosis A (NIMA)-related protein kinases, mitogen-activated protein (MAP) kinases, and a novel cyclin dependent protein kinase--are involved in the ciliary regulation process. Among the newly identified protein kinase substrates are Chlamydomonas kinesin-13 (CrKinesin13), a microtubule depolymerizer, and histone deacetylase 6 (HDAC6), a microtubule deacetylase. Chlamydomonas aurora/Ipl1p-like protein kinase (CALK) and CrKinesin13 are two proteins that undergo phosphorylation changes correlated with flagellar assembly or disassembly. CALK becomes phosphorylated when flagella are lost, whereas CrKinesin13 is phosphorylated when new flagella are assembled. Conversely, suppressing CrKinesin13 expression results in cells with shorter flagella. PMID- 20362100 TI - Posttranslational protein modifications in cilia and flagella. AB - Tubulin and other flagellar and ciliary proteins are the substrates for a host of posttranslational modifications (PTMs), many of which have been highly conserved over evolutionary time. In addition to the binding of MAPs (microtubule associated proteins) that provide a specific functionality, or the use of different tubulin isotypes to convey a specific function, most cells rely on an array of PTMs. These include phosphorylation, acetylation, glycylation, glutamylation, and methylation. The first and the last of this list are not unique to the tubulin in cilia and flagella, while the others are. This chapter will review briefly these varying modifications and will conclude with detailed methods for their detection and localization at the limit of resolution provided by electron microscopy. PMID- 20362196 TI - Maintaining the value of an optometric practice. PMID- 20362197 TI - A quick method of assessing third-party plans. PMID- 20362199 TI - Antibodies to serotype 9V exhibit novel serogroup cross-reactivity following infant pneumococcal immunization. AB - Cross-reactivity within the pneumococcal immune response was examined in this study. Significant cross-reactivity between serotypes 9V, 15B and 19A was identified in infant post-immunization serum that could not be effectively titrated during specific IgG measurements. Pre-absorption using serotype 9V inhibited this cross-reactivity and normalized titratability in the WHO ELISA for serotypes 15B and 19A. However, this did not affect functional avid IgG and was associated with fewer pneumococcal conjugate vaccine (PCV) doses, suggesting that cross-reactive antibodies were of low avidity. The results in this study have important implications for assessment of vaccine immunogenicity. PMID- 20362200 TI - Variable-number tandem repeat markers for identification of Brucella abortus 82 and 75/79-AV vaccine strains. AB - In Russia, live vaccine strains Brucella abortus 82 and B. abortus 75/79-AV have been widely and extensively utilized for specific prophylaxis of cattle brucellosis. To differentiate these vaccine strains from each other and laboratory collection of other vaccine (n=4), reference (n=15) and field Brucella strains (n=61), the multiple-locus variable-number tandem repeat (VNTR) analyses (MLVA) were used with 12 loci containing tandem repeats from 134bp to 8bp recently described for Brucella spp. The results obtained by MLVA typing revealed that the vaccines are genetically closely related. Three sufficiently stable in vitro VNTR loci were chosen in order to discriminate, in single tube Multiplex PCR, products of the vaccine strains from the other Brucella strains. Our results demonstrated that MLVA in Multiplex PCR format is a rapid, easy, economical and efficient tool for identification of vaccine strains and will be validated in future large scale typing of Brucella isolates circulating in Russia. PMID- 20362202 TI - Targeted prevention of brucellosis in cattle, sheep, and goats in the Russian Federation. AB - The article presents a brief history of the brucellosis prevention in animals in the world and in the Russian Federation. Data are taken from studies on the immunogenic activity and epizootic efficacy of vaccines against brucellosis in animals, which made it possible, in the final analysis, to regard these preparations as highly important for brucellosis prevention. The relationship between the epizootic brucellosis situation in Russia and the employment of specific agents in targeted prevention of brucellosis in cattle, sheep, and goats, and the sequence of their use, are presented briefly, substantiating the feasibility of their use and improvement. PMID- 20362201 TI - Comparative study of the immunobiological properties of live brucellosis vaccines. AB - Findings from the comparative study of the immunobiological properties of live brucellosis vaccines in guinea pigs are presented in the article. Vaccines from strains Brucella abortus 19 (U.S.) and 82 (Russia), in the S and SR forms, respectively, exhibited the highest and most pronounced immunological efficacy, while vaccines from strains B. abortus 82-PS (in the RS form) and B. abortus RB 51 and 75/79-AB (in the R forms) exhibited the lowest. The live vaccine from strain B. abortus 82, together with a high immunological activity, possesses inagglutinogenic properties. The great advantage of this vaccine over the vaccine from strain B. abortus 19 is that after its use in animals the problem of the differential diagnosis of brucellosis becomes much simpler. The live vaccine from strain B. abortus 82 was adopted in veterinary practice in the Russian Federation; it is widely used for the targeted prevention of bovine brucellosis, but can also be used successfully for wild animals such as bison, deer, elk, and others. PMID- 20362203 TI - Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection. AB - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The fusion (F) protein of RSV is a potentially important target for protective antiviral immune responses. Here, we studied the immune responses elicited by recombinant replication deficient adenovirus (rAd)-based vaccines expressing the soluble F1 fragment of F protein (amino acids 155-524) in murine model. The expression of secreted F1 fragment by rAd was significantly increased by codon optimization. Strong mucosal IgA response was induced by single intranasal immunization of codon-optimized vaccine, rAd/F1co, but not by rAd/F1wt. A single intranasal immunization with rAd/F1co provided potent protection against subsequent RSV challenge. Interestingly, neither serum Ig nor T-cell response directed to F protein was detected in the rAd/F1co-immune mice, suggesting that protective immunity by rAd/F1co is mainly mediated through mucosal IgA induction. Indeed, co-delivery of cholera toxin B subunit significantly enhanced mucosal IgA responses by the optimized vaccine, which correlates with protective efficacy. Taken together, our data demonstrate that a single intranasal administration of rAd/F1co is sufficient for the protection and represents a promising prophylactic vaccination regimen against RSV infection. PMID- 20362204 TI - Immune response induced by a linear DNA vector: influence of dose, formulation and route of injection. AB - Previously, minimalistic, immunogenetically defined gene expression (MIDGE) vectors were developed as effective and sophisticated carriers for DNA vaccination. Here we evaluate the influence of dose, formulation and delivery route on the immune response after vaccination with MIDGE-Th1 vectors encoding hepatitis B virus surface antigen (HBsAg). An HBsAg-specific IgG1 and IgG2a antibody response was induced in a dose-dependent manner, whereas the IgG2a/IgG1 ratio was independent of the injected DNA dose. Formulation of MIDGE-HBsAg-Th1 with the cationic pyridinium amphiphile SAINT-18 significantly increased antibody levels of IgG1 and IgG2a compared to the unformulated vector. In contrast, SAINT 18 had neither a significant effect on the IgG2a/IgG1 ratio nor on the type and strength of cellular immunity. Overall, the strongest immune response was generated after intradermal injection, followed by intramuscular and subcutaneous (s.c.) injection. The results show that the formulation of MIDGE-Th1 with SAINT 18 increased the efficacy of the MIDGE-Th1 DNA vaccine and is therefore a suitable approach to improve the efficacy of DNA vaccines also in large animals and humans. PMID- 20362205 TI - Evaluating the virulence of a Brucella melitensis hemagglutinin gene in the caprine model. AB - With the completion of the genomic sequence of Brucella melitensis 16M, a putative hemagglutinin gene was identified which is present in 16M and absent in Brucella abortus. The possibility of this hemagglutinin being a potential virulence factor was evaluated via gene replacement in B. melitensis yielding 16MDeltaE and expression in trans in B. abortus 2308-QAE. Utilizing the caprine brucellosis model, colonization and pathogenesis studies were performed to evaluate these strains. B. melitensis 16M hemagglutinin gene expression in trans in 2308-QAE revealed a significant (p<=0.05) increase in colonization and abortion rates when compared to B. abortus 2308, mimicking B. melitensis 16M virulence in pregnant goats. The B. melitensis disruption mutant's colonization and abortion rates demonstrated no attenuation in colonization but displayed a 28% reduction in abortions when compared to parental B. melitensis 16M. PMID- 20362206 TI - Hepatitis B virus (HBV)-derived DRB1*0101-restricted CD4 T-cell epitopes help in the development of HBV-specific CD8+ T cells in vivo. AB - We previously identified two HLA-DRB1*0101-restricted epitopes in hepatitis B virus (HBV) X protein (HBx) and in HBV envelope proteins (preS2). To evaluated their help in the development of CD8+ T-cell responses, mice transgenic for human class I and class II HLA molecules were immunized with HBV-T helper constructs. The preS2 epitope favored a well-balanced response with CD4+ and CD8+ T cells producing IFN-gamma, IL-2 and TNF-alpha. The response was focused on CD8+ T cells with the HBx epitope. Fine characterization of helper activities may meet clinical needs in terms of enhancing the potency of preventive or therapeutic polyepitope vaccines. PMID- 20362208 TI - FOCUSing on safety. PMID- 20362209 TI - Clarifications on RNFA education programs from the Competency & Credentialing Institute. PMID- 20362210 TI - Safe handling of chemotherapy in the perioperative setting. AB - Safe handling of chemotherapeutic agents during administration and disposal is critical. Most antineoplastic agents are toxic compounds that are carcinogenic, mutagenic, or teratogenic. Direct contact may cause irritation of the skin, eyes, and mucous membranes. Perioperative personnel should know how to handle hazardous materials safely to protect the patient, other staff members, and themselves. These safety precautions include appropriately identifying the patient; correctly preparing, verifying, and documenting the chemotherapeutic agents being administered; consistently wearing personal protective equipment; transporting the chemotherapeutic agent in a puncture-resistant container labeled "chemotherapy"; properly disposing of the chemotherapeutic agent and supplies; and handling a spill if one occurs. PMID- 20362211 TI - Collaboration between perioperative nurses and sterile processing department personnel. AB - Ensuring patient safety requires collaboration between all members of the surgical team, which includes personnel in the sterile processing department. Because of the close working relationship between the OR and sterile processing department, it is important that employees in these departments work well together. Reducing errors and misunderstandings can contribute to improved relationships between personnel in these two departments. Strategies should include a focus on reducing instrument set errors, fostering teamwork and positive relationships, improving interdepartmental communication, and ensuring compliance with policies that are based on the most current evidence available. PMID- 20362212 TI - New recommendations for prevention of surgical fires. PMID- 20362213 TI - Stress urinary incontinence: a review of treatment options. AB - Stress urinary incontinence occurs when the support structures of the pelvic floor and the urinary system are stretched, damaged, or defective. This condition is common in women of all ages, and billions of dollars are spent each year to correct the condition and improve quality of life. This article reviews three current treatments for stress urinary incontinence: the Burch colposuspension procedure, urethral slings, and radiofrequency treatments. In one study, researchers reported that patient satisfaction rates were higher for the Burch procedure than for urethral sling procedures. Other researchers found that urethral sling procedures had high rates of success but that adverse events were more common. Adverse events for both types of procedures include voiding difficulties, postoperative urge incontinence, and urinary tract infections. Radiofrequency interventions can improve the quality of life for many patients and can provide a short-term intervention for many patients who later may require a more-invasive surgical procedure. PMID- 20362214 TI - Management of exposure to waste anesthetic gases. AB - Anesthetic agents were developed in the 1700s, and nitrous oxide was first used in 1884. Research on the effects of waste anesthetic gas exposure started appearing in the literature in 1967. Short-term exposure causes lethargy and fatigue, and long-term exposure may be linked to spontaneous abortion, congenital abnormalities, infertility, premature births, cancer, and renal and hepatic disease. Today, perioperative staff members are exposed to trace amounts of waste anesthetic gas, and although this exposure cannot be eliminated, it can be controlled. Health care facilities are required to develop, implement, measure, and control practices to reduce anesthetic gas exposure to the lowest practical level. Exposure levels must be measured every six months and maintained at less than 25 parts per million for nitrous oxide and 2 parts per million for halogenated agents to be compliant with Occupational Safety and Health Administration standards. PMID- 20362215 TI - Creating a culture of mutual respect. AB - The Joint Commission mandates that hospitals seeking accreditation have a process to define and address disruptive behavior. Leaders at Maimonides Medical Center, Brooklyn, New York, took the initiative to create a code of mutual respect that not only requires respectful behavior, but also encourages sensitivity and awareness to the causes of frustration that often lead to inappropriate behavior. Steps to implementing the code included selecting code advocates, setting up a system for mediating disputes, tracking and addressing operational system issues, providing training for personnel, developing a formal accountability process, and measuring the results. PMID- 20362216 TI - Caring for the perioperative patient with increased intracranial pressure. PMID- 20362219 TI - Listen to the family. PMID- 20362220 TI - Reinforcing effects of smoking: more than a feeling. PMID- 20362221 TI - Natural and engineered resistance to plant viruses, part II. Preface. PMID- 20362222 TI - High-resolution genomic profiling to predict 10-year overall survival in node negative breast cancer. AB - Women with clinically node-negative breast cancer have a better prognosis than do those with axillary lymph node metastasis. Nonetheless, approximately 20% of node negative patients die within 15 years of diagnosis, and thus additional prognostic markers are greatly needed. To identify specific copy number alterations (CNAs) that differed in frequency between 10-year survivors and deceased patients with node-negative breast cancer, array comparative genomic hybridization (aCGH) was applied to 41 primary node-negative breast tumors. Fisher's exact test was used to identify significantly different CNAs between 10 year survivors and deceased patients. Losses at 8p21.2 approximately p21.3, 8p23.1 approximately p23.2, Xp21.3, and Xp22.31 approximately p22.33 were significantly more common in tumors from deceased patients, suggesting that these alterations may contribute to tumor aggressiveness. Gains at 1q25.2 approximately q25.3 and 1q31.3 approximately q41 were more prevalent in tumors from survivors; specific gains at these genomic regions may inhibit further tumor progression, resulting in a less aggressive form of node-negative breast cancer. Evaluation of the identified CNAs in an independent external data set verified the prognostic potential of the 1q31.3 approximately q41 region. Although further extensive validation is needed, the prognostic CNAs identified in this work may in time facilitate the clinical assessment of breast cancer. PMID- 20362223 TI - Antitumor effect and mechanisms of arsenic trioxide on subcutaneously implanted human gastric cancer in nude mice. AB - We sought to investigate the efficacy of arsenic trioxide (As(2)O(3)) against a human gastric cell line implanted in nude mice in vivo, as well as the mechanism involved. The solid tumor model was created in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into animals in two arsenic-treated groups (2.5 mg/kg and 5 mg/kg), and the same volume of saline solution was injected into the control group. The inhibitory effect was observed in every group. Apoptotic cells and apoptotic bodies were observed by transmission electron microscope; the fraction of apoptotic cells was detected by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) under laser confocal technology. The expression of Fas and FasL was detected by immunohistochemical staining. In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3), approximately 50% and 30% tumor growth inhibition were observed, respectively (P < 0.05 for both treatment groups). Increase in apoptotic cells and apoptotic bodies appeared in As(2)O(3) treated tumors compared with the control group. The fluorescence intensity levels of apoptotic cells in tumor were significantly higher in the arsenic-treated groups (P < 0.05 for both treatment groups). The fluorescence intensity level of apoptotic cells in the 5-mg/kg group was higher than that in the 2.5-mg/kg group (P < 0.05). The expression of Fas protein increased in dose- and time-dependent manner after the treatment with As(2)O(3), but that of FasL protein showed no significant difference between control and treated groups. As(2)O(3) did not induce hepatic and renal system injury in the nude mice. As(2)O(3) can inhibit the growth of human gastric cell implanted tumor. We ascribe this to upregulation of Fas, which can induce apoptosis of gastric cells. PMID- 20362224 TI - Comparative proteomics analysis of human osteosarcomas and benign tumor of bone. AB - We conducted comparative proteomic analysis of osteosarcoma, with hopes of identifying the specific protein markers of osteosarcoma and improve the understanding of tumorigenesis and progression of osteosarcoma. Proteins extracted from osteosarcoma tissue and benign bone tumors, including osteoblastoma, chondroblastoma, and giant cell tumor of bone, were examined using two-dimensional gel electrophoresis followed by mass spectrometry analysis and database searches. We also validated the expression levels of interesting proteins by Western blotting assay and immunohistochemical staining. Intensity alterations of 30 spots were detected in osteosarcoma, and 18 of these spots were finally identified, including 12 up-regulated proteins and 6 down-regulated ones. The up-regulated proteins include VIM, TUBA1C, ZNF133, EZR, ACTG1, TF, and so on. The six down-regulated proteins include ADCY1, ATP5B, TUBB, RCN3, ACTB, and YWHAZ. Subsequent immunohistochemical staining and Western blotting assay for TUBA1C and ZNF133 in osteosarcoma samples confirmed the observation obtained by proteomic analysis. Our results suggest that these identified proteins may be potential biomarkers for osteosarcoma tumorigenesis and therapeutics. Aberrant expression of cytoskeletal- and microtubule-associated proteins in osteosarcoma may provide an advantage for tumor invasion and metastasis by affecting the stability of microtubule, which consequently influences the prognosis of patients. PMID- 20362225 TI - Analysis of fluorescence in situ hybridization, mtDNA quantification, and mtDNA sequence for the detection of early bladder cancer. AB - We designed this study to test the sensitivities of cytology, the nuclear matrix protein 22 (NMP22) assay, and fluorescence in situ hybridization (FISH) in the early detection of urothelial carcinoma, and to identify mtDNA alterations in urinary epithelial cells. We collected 41 urine samples and 26 corresponding peripheral blood samples from patients with clinically suspected urothelial carcinoma. The FISH and NMP22 assays detected 92.1% of the cancers, and cytology detected 60.5%. In the low-grade group, NMP22 and FISH analyses were more sensitive than cytology, but in the high-grade group, all three methods showed approximately 90% sensitivity. Overall, the FISH and NMP22, or FISH and cytology assays combined detected 97.4% of cancers, while cytology with NMP22 detected 92.1%. In the low-grade group, the sensitivity of the three methods combined was above 80%, but in high-grade group, the combined sensitivity was approximately 100%. In the mtDNA control region, we detected characteristic heteroplasmic mtDNA substitution mutations in 1 patient and a mtDNA length heteroplasmic mutation in 303 polyC or 16184 poly C in 20 patients. Overall, urothelial carcinoma-specific mtDNA mutations were observed in 20 of the 26 patients (76.9%). The average mtDNA copy numbers in urine samples and corresponding peripheral blood samples (83.45 +/- 60.36 and 39.0 +/- 24.38, respectively) (mean +/- standard deviation [SD]) differed significantly (P < 0.001). The mtDNA copy numbers in the urine samples from patients with high-grade and low-grade tumors (81.83 +/- 67.78 and 86.49 +/- 46.69, respectively) did not differ significantly (P = 0.589). In conclusion, the FISH assay showed the highest sensitivity for detecting low-grade urothelial carcinoma, and mtDNA copy numbers in urine samples were higher than those in the corresponding peripheral blood samples. The frequency of mtDNA mutations in the D loop region in patients with cancer was approximately 80% in our study. This report further supports the significance of genetic alteration in urothelial carcinoma and the clinical utility of the FISH, mtDNA quantitation polymerase chain reaction, mtDNA sequencing, and capillary electrophoresis for this purpose. PMID- 20362226 TI - PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. AB - DNA copy number aberrations in human hepatocellular carcinoma (HCC) cell lines were investigated using a high-density oligonucleotide microarray, and a novel amplification at the chromosomal region 7q21 was detected. Molecular definition of the amplicon indicated that PEG10 (paternally expressed gene 10), a paternally expressed imprinted gene, was amplified together with CDK14 (cyclin-dependent kinase 14; previously PFTAIRE protein kinase 1, PFTK1) and CDK6 (cyclin-dependent kinase 6). An increase in PEG10 copy number was detected in 14 of 34 primary HCC tumors (41%). PEG10, but not CDK14 or CDK6, was significantly overexpressed in 30 of 41 tumors (73%) from HCC patients, compared with their nontumorous counterparts. These results suggest that PEG10 is a probable target, acting as a driving force for amplification of the 7q21 region, and may therefore be involved in the development or progression of HCCs. PMID- 20362227 TI - Heterozygosity status of 1p and 19q and its correlation with p53 protein expression and EGFR amplification in patients with astrocytic tumors: novel series from India. AB - There are few reports of loss of heterozygosity (LOH) of 1p and 19q in astrocytic tumors, especially glioblastoma multiforme (GBM). We evaluated 1p and 19q (either or both) heterozygosity status in 71 astrocytomas, including 6 pediatric cases: 20 diffuse astrocytomas (DA), 9 anaplastic astrocytomas (AA), and 42 GBM. In the GBMs, p53 protein expression was assessed by immunohistochemistry and epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization; TP53 sequencing was done in 15 of the GBMs. In adults, LOH of 1p or 19q was detected in 16% of DAs and 50% of GBMs; none of the AAs showed this alteration. In GBMs, LOH of 19q was most common (26%), followed by combined 1p and 19q LOH (13%) and 1p LOH (10%). Pediatric GBMs also harbored isolated 1p and 19q LOH (50%). Notably, LOH of 1p or 19q LOH was more frequent in p53 immunopositive secondary GBMs (61%) than in primary GBMs (17%). This suggests that LOH of 1p and 19q may be acquired during progression to secondary GBMs. Thus, 1p and 19q LOH can occur in astrocytic tumors, most commonly in secondary GBMs without morphological correlation with an oligodendroglial histology. The clinical significance of recognition of this subset of GBMs is based on several recent reports of association with better prognosis, although long-term follow-up studies are required. PMID- 20362229 TI - Clinical usefulness of fluorescence in situ hybridization for diagnosis and surveillance of bladder cancer. AB - We evaluated the performance of the fluorescence in situ hybridization (FISH) assay in comparison with that of urinary cytology for the detection of bladder urothelial carcinoma in routine clinical practice. Voided urine samples from 602 patients with hematuria were analyzed. The bladder cancer group consisted of 95 patients who had biopsy-proven bladder cancer, and the control group consisted of 507 patients without bladder cancer. We found a significant difference between the overall sensitivities of FISH and cytology (60% vs. 28.4%, respectively; P < 0.0001). The overall specificity was 99% with cytology and 94.9% with FISH, although this difference was not statistically significant. The mean values for all four probes in the true-positive group were higher than those in the false positive group. The difference in the mean values between the two groups was significant only for the CEP3 and CEP17 probes. Furthermore, the severity of the genetic alterations detected by FISH showed a positive correlation with both tumor invasiveness (stage Ta --> T1, T2) and histological grade (G1, G2 --> G3). Together, these findings suggest that FISH can be a useful diagnostic and surveillance tool for patients who are suspected of having new or recurrent bladder cancer. PMID- 20362228 TI - Cytogenetic studies in acute leukemia patients relapsing after allogeneic stem cell transplantation. AB - We analyzed karyotype stability in 22 patients with acute leukemia at relapse or disease progression after allogeneic stem cell transplantation (allo-SCT). Karyotypes before and at relapse after allo-SCT were different in 15 patients (68%), the most frequent type being clonal evolution either alone or combined with clonal devolution (13 patients). Patients with and without a karyotype change did not differ significantly in overall survival (OS) (median, 399 vs. 452 days; P = 0.889) and survival after relapse (median, 120 vs. 370 days; P = 0.923). However, acquisition of additional structural chromosome 1 abnormalities at relapse after allo-SCT occurred more frequently than expected and was associated with reduced OS (median, 125 vs. 478 days; P = 0.008) and shorter survival after relapse (median, 37 vs. 370 days; P = 0.002). We identified a previously undescribed clonal evolution involving t(15;17) without PML-RARA rearrangement in an AML patient. We conclude that a karyotype change is common at relapse after allo-SCT in acute leukemia patients. Moreover, our data suggest that additional structural chromosome 1 abnormalities are overrepresented at relapse after allo-SCT in these patients and, in contrast to a karyotype change per se, are associated with reduced OS and shorter survival after relapse. PMID- 20362230 TI - Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia. AB - Genetic aberrations involving the mixed lineage leukemia (MLL) gene are frequently diagnosed in infant acute lymphoblastic and acute myeloid leukemia. More than 60 fusion partner genes have been described at the molecular level, 31 of which have been characterized solely in infant leukemia cases. Here we describe a new MLL fusion partner gene, NEBL, which was identified in a case of acute myeloid leukemia in an infant. The chromosomal breakpoints of the MLL-NEBL and NEBL-MLL fusion genes were cloned by long-distance inverse polymerase chain reaction. The chromosomal breakpoints were located at 10p12, approximately 570 kb telomic of the MLLT10 (AF10) gene. AF10 and NEBL are localized in such close vicinity that they cannot be distinguished cytogenetically by G banding. Therefore, the combination of cytogenetic and independent molecular techniques such as long-distance inverse polymerase chain reaction are indispensable for the rapid identification and characterization of rare MLL rearrangements. PMID- 20362231 TI - Cytogenetic investigations of chronic lymphocytic leukemia. AB - This study aimed to determine which culture method would yield the highest culture success rate, mitotic index, banding resolution, and abnormality rate in investigation of patients with chronic lymphocytic leukemia (CLL). A range of culture techniques for conventional cytogenetic (CC) analyses was compared: 24 hour unstimulated, 72 hours incubation with additional fetal calf serum, 72 hours stimulation with interleukin 4, 72 hours stimulation with lipopolysaccharide (LPS), 72 hours stimulation with TPA (12-O-tetradecanoylphorbol 13-acetate), and 72 hours stimulation with CpG-oligonucleotide DSP30 + Interleukin-2 (IL-2). CC abnormality rates were also compared to fluorescence in situ hybridization (FISH) results using probes for CLL (LSI D13S319/13q34/CEP 12: LSI ATM/p53). Forty-five samples from 24 patients (consisting of 11 newly diagnosed and 13 previously diagnosed patients) were included. For CC, a 100.0% culture success rate was achieved (n = 45) by means of an EDTA (ethylenediaminetetraacetic acid) peripheral blood sample with an associated 62.5% CC abnormality rate (n = 24). FISH detected an abnormality rate of 75.0% (n = 24). The combined CC and FISH abnormality rate was 87.5% (n = 24). This study demonstrates that CC that uses TPA and DSP30 + IL-2 on EDTA peripheral blood is effective in the investigation of CLL and may be used as a supplement to FISH studies. PMID- 20362232 TI - JAK2 V617F-positive essential thrombocythemia in a patient with Klinefelter syndrome: a case report. AB - Klinefelter syndrome (KS) is the most commonly diagnosed X chromosome aneuploid syndrome among males. The association between hematologic malignancies such as non-Hodgkin lymphoma and leukemia and KS has been established recently on the basis of numerous case reports and a large cohort study. The risk of chronic myeloproliferative disease (MPD) as a hematologic malignancy in KS, however, has not been evaluated to date. Moreover, to our knowledge, there is only one case report that observed MPD in a patient with KS. Even though the Janus kinase 2 (JAK2) mutation was considered the primary cause in the pathogenesis of MPD, the mutation status was not described in that report. We found JAK2 V617F mutation positive essential thromobocythemia (ET) in a patient with KS. To the best of our knowledge, this case represents the first case report of JAK2 V617F mutation in a patient with KS. Furthermore, we also suggest the hypothesis that X chromosome aneuploidy as a "pre-JAK2" cytogenetic change may be associated with the development of clonal hematopoiesis and carcinogenesis, because of the finding of higher oncogenic potential of extra X chromosome. In this study, we present the first report of JAK2 V617F-positive ET in a patient with KS, as well as a review of the relevant literature. PMID- 20362233 TI - Tetrasomy 8 in a patient with chronic lymphocytic leukemia. AB - We report a case of a 47-year-old man diagnosed with chronic lymphocytic leukemia (CLL) with two extra copies of chromosome 8. Classical cytogenetic analysis by the immunostimulatory combination of DSP30 and interleukin 2 showed tetrasomy of chromosome 8 in 60% of the metaphase cells (48,XY,+8,+8[12]/46,XY[8]). Spectral karyotype analysis confirmed the abnormality previously seen by G banding. Additionally, interphase fluorescence in situ hybridization using an LSI CEP 8 probe performed on peripheral blood cells without any stimulant agent showed tetrasomy of chromosome 8 in 54% of analyzed cells (108 of 200). To our knowledge, tetrasomy 8 as the sole chromosomal abnormality in CLL has not been previously described. The prognostic significance of tetrasomy 8 in CLL remains to be elucidated. However, the patient has been followed up in the outpatient hospital since 2004 without any therapeutic intervention and has so far remained stable. PMID- 20362234 TI - Rapid response to induction in a case of acute promyelocytic leukemia with MYC amplification on double minutes at diagnosis. PMID- 20362235 TI - An intronic variant in the TP53 gene in Serbian women with cervical or ovarian cancer. PMID- 20362236 TI - Heroin-assisted treatment in the Netherlands: History, findings, and international context. AB - This monograph describes the history, findings and international context of heroin-assisted treatment (HAT) in the Netherlands. The monograph consists of (1) a short introduction and seven paragraphs describing the following aspects of HAT in the Netherlands: (2) history of HAT studies and implementation of routine HAT in the Netherlands; (3) main findings on efficacy, safety and cost-effectiveness from the two randomized controlled HAT trials in the Netherlands; (4) new findings from a large cohort study on the effectiveness of HAT in routine clinical practice in the Netherlands; (5) unique data on the patient's perspective of HAT; (6) data on the pharmacological and pharmaceutical basis for HAT in the Netherlands; (7) description of the registration process; and (8) account of the international context of HAT. Together, these data show that HAT can now be considered a safe and proven-effective intervention for the treatment of chronic, treatment-resistant heroin dependent patients. PMID- 20362237 TI - The scope of mycoplasma contamination within the biopharmaceutical industry. AB - Mycoplasma is well recognized as one of the most prevalent and serious microbial contaminants encountered within the manufacturing of biopharmaceuticals from the research phase to clinical development and production. The potential for mycoplasma contamination within cell culture systems was first identified by Robinson et al. in 1956. Presently, contamination rates in established cell cultures have been reported between 15 and 35% with considerably higher occurrence cited in certain selected populations. In the last few years, there has been an expansion of diagnostic approaches for mycoplasma detection with the development and validation of rapid microbiological methods. The objective of this study was to determine current levels of mycoplasma infection of cell cultures, cell substrates and biologicals within a client based population. Retrospective comparison of 40,000 sample results was done to determine total contaminations rates amongst four (4) individual analytical assays. The establishment of reference data, such as existing contamination rates, becomes important in the critical appraisal of rapid microbiological methods for the detection of mycoplasma. PMID- 20362238 TI - Can meta-analysis of the current literature help determine if perioperative beta blockers improve outcome of high-risk patients undergoing noncardiac surgery? PMID- 20362239 TI - Case 2-2010 combined surgery for coronary artery disease, mitral stenosis, and double-chamber right ventricle. PMID- 20362240 TI - Rheumatic mitral and aortic stenosis: to replace or not to replace--that is the question--part 2. PMID- 20362241 TI - Combined valvular disease: when echocardiography provides the questions and the answers. PMID- 20362242 TI - Bilateral and symmetric C1-C2 dumbbell ganglioneuromas associated with neurofibromatosis type 1 causing severe spinal cord compression. AB - BACKGROUND CONTEXT: Ganglioneuromas are rarely located in the cervical region compressing the spinal cord. Only two cases of bilateral and symmetric dumbbell tumor have been reported previously. PURPOSE: The purpose of the study was to present an additional case with bilateral and symmetric dumbbell ganglioneuromas of the cervical spine as part of multiple ganglioneuromas of the spine in a patient with neurofibromatosis type 1 (NF-1). STUDY DESIGN: The study design was a case report. METHODS: A 15-year-old boy with NF-1 presented with a 6-month history of progressive tetraparesis. Magnetic resonance imaging showed voluminous bilateral and symmetric dumbbell masses at the C1-C2 level severely compressing the spinal cord. The spinal cord was also indented by a dumbbell mass at the left C3-C4 level. A systemic imaging survey of the patient showed numerous asymptomatic foraminal and extraforaminal tumors at all neuroforamina of the spine. RESULTS: The result was found to be surgical decompression of the spinal cord by subtotal resections of bilateral tumors at the C1-C2 level and unilateral tumor at the left C3-C4 level alleviated patient symptoms. Histopathological diagnosis was ganglioneuroma for all resected tumors. CONCLUSION: Multiple ganglioneuromas, particularly bilateral and symmetric dumbbell tumors, are extremely rare but could be associated with NF-1. PMID- 20362243 TI - Pneumatocyst, mimicking a sclerotic bony lesion on magnetic resonance imaging. AB - BACKGROUND CONTEXT: Intravertebral pneumatocyst is an uncommon benign lesion, not related to conditions, such as osteomyelitis and postsurgical state, with only a few cases reported in the literature. PURPOSE: The purpose of the study was to report a case of cervical pneumatocyst resembling a sclerotic lesion on magnetic resonance imaging (MRI) and review of literature. STUDY DESIGN/SETTING: The study was designed to be a case report. PATIENT SAMPLE: The patient chosen was a 48 year-old woman with the chief complaint of neck pain and bilateral upper extremity paresthesia of 6 months duration. Neurologic examination and results of routine hematologic and biochemical examination were normal. RESULTS: Cervical spine MRI revealed a low signal bony lesion on T1 and T2 images. Considering the signal characteristics, initial diagnosis of sclerosis was made. Reviewing the cervical X-ray, a round faint lytic lesion was detected. Correlation with cervical computed tomography scan showed the lesion being of air density, compatible with the diagnosis of pneumatocyst. CONCLUSION: Intraosseous pneumatocyst of cervical spine is a benign finding, which needs no specific treatment; however, it must be included in the differential diagnosis of lucent vertebral lesions seen on conventional radiography and should be differentiated from bony neoplasm and osteomyelitis by its characteristic imaging findings. PMID- 20362244 TI - Postoperative spinal epidural hematoma at a site distant from the main surgical procedure: a case report and review of the literature. AB - BACKGROUND CONTEXT: Postoperative spinal epidural hematomas are known complications of spinal surgery. However, to our knowledge, there are no known cases of postoperative spinal epidural hematoma that occurred distant from the portion of the procedure that breached the spinal canal. PURPOSE: To report a case and review the literature on the development of postoperative spinal epidural hematoma at a site distant from the portion of the surgical procedure that breached the spinal canal. STUDY DESIGN: Case report and review of the literature. METHODS: One patient at our institution developed a hematoma at a site distant from the surgical procedure that breached the spinal canal. We retrospectively reviewed the patient's clinical charts, radiographs, and computed tomography scans. RESULTS: A 57-year-old woman with adult scoliosis and junctional kyphosis underwent a pedicle subtraction osteotomy and long spinal fusion from T3 to the sacrum. Three hours postoperatively, she developed paraplegia with a neurologic deficit at a level distant from the site at which the spinal canal was surgically breached. A computed tomography myelogram revealed a spinal epidural hematoma that was causing compression of the spinal cord in the upper thoracic spine. The patient was returned to the operating room emergently and underwent laminectomy and hematoma evacuation. She had near complete recovery 5 months after surgery. CONCLUSION: Spinal epidural hematomas are rare but dangerous complications that can result in severe neurologic deficits. A neurologic examination should always be conducted in the operating room immediately after surgery; if it is abnormal, spinal epidural hematoma should be suspected. If the examination indicates a deficit at a site distant from the original surgery, then diagnostic reimaging (magnetic resonance imaging or computed tomography myelogram) is indicated. PMID- 20362245 TI - The rise and fall of the "minimum clinically important difference". PMID- 20362246 TI - Health-related quality of life: a comparison of outcomes after lumbar fusion for degenerative spondylolisthesis with large joint replacement surgery and population norms. AB - BACKGROUND CONTEXT: Degenerative spine disease will become an increasing health problem, and a significant number of patients will be considered for surgery. Spinal surgeries have evolved since the last decades, and there is a positive impact on the clinical outcomes. Few works in the literature have reviewed the outcome compared with large joint replacement surgery, which is considered a benchmark for operative restoration of patients' quality of life. PURPOSE: The purpose of this study was to investigate if spinal fusion can return patients' health-related quality of life to that of age-matched population norms and yield outcomes comparable with those of total hip and knee joint replacement. STUDY DESIGN: This is a prospective cohort study. PATIENT SAMPLE: The sample consists of 100 consecutive patients who were enrolled between December 1997 and January 2007. OUTCOME MEASURES: The 12-item Short Form Health Survey (SF-12) was chosen for outcome measurement. METHODS: All patients underwent wide decompressive laminectomy and single-level posterior lumbar interbody fusion for spinal stenosis associated with degenerative spondylolisthesis. RESULTS: The preoperative and postoperative physical component summary (PCS)-12 scores of the spinal fusion patients were comparable with those of both the total knee and hip replacement patients. The mean improvement in PCS-12 scores after spine surgery was 11 (95% confidence interval [CI]: 9-14, p<.0001). It was equal to that after total hip replacement surgery, which was 11 (95% CI: 9-13), and higher than that of total knee replacement patients, which had an improvement of 8 (95% CI: 7-9). The postoperative mean and 95% CI of the PCS-12 scores for the three surgical procedures approached the population norm value of 44 (95% CI: 43-46).There was no statistical difference between the postoperative mental component summary-12 score among all the three surgical groups, which approached similar to the population norm value of 54 (95% CI: 53-54). CONCLUSIONS: The current study demonstrated that spinal surgery can return patients' HRQL to that of age-matched population norms and yield outcomes comparable with those of total hip and knee joint replacement patients. PMID- 20362247 TI - Minimum acceptable outcomes after lumbar spinal fusion. AB - BACKGROUND CONTEXT: Defining success after spinal surgery remains problematic. The minimal clinically important difference (MCID) in pain or functional outcomes is a common metric often calculated independent of perceived risk and morbidity, which is an important consideration in large procedures such as spinal fusion and instrumentation. PURPOSE: The purpose of this study was to describe a method of assessing treatment success based on prospective, patient-reported "minimum acceptable" outcome for which they would undergo a procedure. These goals can then be compared at follow-up to gauge how frequently patient goals are met and determine correlation with patient satisfaction. STUDY DESIGN: This is a clinical descriptive study of the patient-reported minimum acceptable outcomes for spinal fusion surgery. OUTCOME MEASURES: Minimum acceptable outcomes were determined by patients on preoperatively administered standard questionnaires regarding ultimate pain intensity, functional outcome (Oswestry Disability Index [ODI]), medication usage, and work status. Satisfaction with outcomes was assessed at 2 year follow-up. METHODS: One hundred sixty-five consecutive patients undergoing lumbar fusion for either isthmic spondylolisthesis or disc degeneration were asked to preoperatively define on standard questionnaires their minimum acceptable outcomes after surgery. Two-year outcomes and satisfaction were subsequently reported and compared with the preoperatively determined minimum acceptable outcomes. RESULTS: Both the spondylolisthesis and the degenerative disc disease (DDD) groups reported that a high degree of improvement was the minimum acceptable threshold for considering spinal fusion. A large majority indicated that the minimum acceptable outcomes included at least a decrease in pain intensity to 3/10 or less, an improvement in ODI of 20 or more, discontinuing opioid medications, and return to some occupational activity. Achieving the minimum acceptable outcome was strongly associated with satisfaction at 2 years after surgery. Patients with compensation claims, psychological distress, and other psychosocial stressors were more likely to report satisfaction in the absence of achieving their minimum acceptable outcome. CONCLUSIONS: Patients with spondylolisthesis and DDD both have relatively high minimum acceptable outcomes for spinal fusion. In these cohorts, few subjects considered more commonly proposed MCIDs for pain and function as an acceptable outcome and report that they would not have surgery if they did not expect to achieve more than those marginal improvements. Although there was good concordance between achieving the minimum acceptable outcomes and ultimate satisfaction, patients with significant psychosocial factors (compensation claims, psychological distress, and others) are less likely to associate satisfaction with outcomes with actually achieving these improvements. PMID- 20362248 TI - Testing minimal clinically important difference: consensus or conundrum? AB - BACKGROUND CONTEXT: Various methodologies have been used in attempting to elucidate a standard method for calculating minimal clinically important difference (MCID). A consensus-based decision (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials [IMMPACT] group) suggested a 30% reduction from baseline as a means to define the MCID of self-report back pain measures. Additionally, important psychometric issues need to be addressed regarding use of an independent measure of the same construct as an external criterion, instead of simply using another self-report measure, when using an anchor-based approach to MCID. PURPOSE: The purpose was to test the validity of recently published guidelines regarding MCID using self-report back pain measures and objective socioeconomic outcomes. STUDY DESIGN/SETTING: This is a prospective study assessing change scores on commonly used spinal pain assessment measures in patients with chronic disabling occupational spinal disorders (CDOSDs) treated in a regional referral rehabilitation center performing interdisciplinary functional restoration. PATIENT SAMPLE: The study consisted of consecutive cohort of patients (N=1,180) with CDOSDs completing a functional restoration program. OUTCOMES MEASURES: Self-report measures including the Oswestry Disability Index (ODI) and the physical component summary (PCS) and mental component summary (MCS) of the Short Form-36 (SF-36) obtained before and after treatment, were compared with objective socioeconomically relevant outcomes obtained 1 year after treatment (ie, work status and additional health-care utilization), that were the external criteria for evaluating MCID. METHODS: Pre- to posttreatment improvement was calculated separately for each measure, and subjects were divided into two groups based on the change in scores relative to baseline: 30% or greater versus less than 30% improvement. One-year posttreatment objective socioeconomic outcomes were used as independent external criteria relevant to the CDOSD population. This population is often studied as the most costly and problematic cohort in spine care. RESULTS: The ODI and SF-36 MCS were not associated with any of the objective 1-year outcomes used as external criteria. Reduced post rehabilitation health-care utilization (based on the percentage of patients pursuing health care from a new provider) was weakly associated with 30% or greater improvement on the SF-36 PCS, relative to patients whose scores changed by less than 30% relative to baseline (17.0% vs. 21.1%). The same was true for the ODI and return-to-work. CONCLUSIONS: When objective and independent criteria are used (socioeconomic outcomes) in a CDOSD cohort, the 30% improvement in the ODI and SF-36 may not be a valid MCID index. This replicates similar conclusions made by an independent research group using a distribution-based approach to MCID. The validity of the MCID concept rests on future research using objective external criteria. Moreover, there remains a question whether the term "important" in MCID can be unequivocally and operationally defined as a reliable construct. PMID- 20362249 TI - Thresholds for Health-related Quality of Life measures: reality testing. PMID- 20362250 TI - Testing minimal clinically important difference: additional comments and scientific reality testing. PMID- 20362251 TI - The effect of implant size and device keel on vertebral compression properties in lumbar total disc replacement. AB - BACKGROUND CONTEXT: Vertebral end plate support is necessary for successful lumbar total disc replacement (TDR) surgery. Failure to achieve anterior column support as a result of lumbar TDR device undersizing could lead to implant subsidence and fracture. PURPOSE: The purpose of the study was to examine the compressive biomechanical behavior of the vertebral end plate with varying sizes of disc replacement implants. STUDY DESIGN: The study design comprises a biomechanical investigation using a human cadaveric lumbar spine model. METHODS: Fifty-six vertebrae with intact posterior elements were prepared from 13 fresh frozen lumbar spines. Peripheral quantitative computed tomography was performed to assess regional bone density. Vertebrae were potted and subjected to nondestructive compression testing with a small, medium, and large custom-made implants with the footplate geometry of the ProDisc-L TDR (Synthes Spine, West Chester, PA, USA) system and having no keel. Failure testing was performed using the ProDisc-L implant with an intact keel. Pressure sensor film was used to assess contact pressure and distribution. RESULTS: There was a linear correlation between percent coverage of the end plate and implant-end plate stiffness (p=.0001) and an inverse correlation with displacement (p=.01). The difference in implant-end plate stiffness between small-medium, medium-large, and small-large implants was 10.5% (p=.03), 10.2% (p=.02), and 19.6% (p<.0001), respectively. Failure analysis revealed similar trends for implant sizing, but only bone density was found to significantly correlate with failure properties (r=0.76, p<.0001). There was a significant reduction in implant-end plate stiffness of 18% when the keel was intact compared to without the keel (range 6-27%, p=.0008). Pressure film analysis revealed that the implant was loaded peripherally and did not have central contact during nondestructive loading. There was a trend toward greater contact pressure with the small implant when compared with the medium implant (p=.06) and the large implant (p=.06). CONCLUSIONS: Although larger implants reduce end plate displacement, increase apparent implant-end plate stiffness, increase the implant-end plate contact area, and decrease the peak contact pressures, low bone density reduces failure properties. The keel introduces a reduction in stiffness to the implant-end plate interface, the clinical significance of which is currently unknown. PMID- 20362252 TI - Biomechanical comparison of single- and two-level cervical arthroplasty versus arthrodesis: effect on adjacent-level spinal kinematics. AB - BACKGROUND CONTEXT: The use of motion-preserving spinal implants versus conventional arthrodesis instrumentation systems, which stabilize operative segments, necessitates improved understanding of their effect on spinal kinematics and the biomechanically optimal method for surgical reconstruction. PURPOSE: The primary objective of this study was to measure operative- and adjacent-level kinematics after single- and two-level cervical arthroplasty and compare them with those after anterior cervical arthrodesis. A secondary objective was to locate the centers of intervertebral rotation at the operative and adjacent levels after arthroplasty and compare them to those after arthrodesis. STUDY DESIGN: This biomechanical study used an in vitro human cadaveric model to compare the multidirectional flexibility kinematics of single- versus two-level cervical disc arthroplasty reconstructions. METHODS: Eight cadaveric cervical spines (C2-T2) were biomechanically evaluated between Levels C4 and T1 in the intact condition and under the following reconstructions: single level arthroplasty (C6-C7) using porous coated motion (PCM) device; single-level arthrodesis (C6-C7) using interbody cage with anterior plate; two-level arthroplasty (C5-C7) using PCM devices; two-level hybrid treatment of arthroplasty (C5-C6) using PCM device and arthrodesis (C6-C7) using cage/plate; and two-level arthrodesis (C5-C7) using cage/plate. Multidirectional flexibility testing used the Panjabi hybrid testing protocol, including pure moments for the intact condition with overall spinal motion replicated under displacement control for subsequent reconstructions. Unconstrained intact moments of +/-3.0 Nm were used for axial rotation, flexion-extension, and lateral bending testing with quantification of the operative- and adjacent-level range of motion (ROM) and neutral zone. The calculated centers of intervertebral rotation were compared for all intervertebral levels under flexion-extension conditions. RESULTS: Axial rotation loading demonstrated a significant decrease in the C6-C7 ROM for the single-level arthrodesis group compared with the intact spine and the single level arthroplasty group (p<.05). No differences were observed between the intact and single-level arthroplasty groups (p>.05). For the two-level hybrid treatment group, the C5-C6 ROM significantly increased compared with the intact, single level arthroplasty, and two-level arthrodesis groups (p<.05). Moreover, a significant increase was observed in the adjacent-level (C7-T1) ROM for the two level arthrodesis group compared with all other treatment groups (p<.05). Under flexion-extension, no differences were observed in C6-C7 ROM between the intact spine and single-level arthroplasty groups (p>.05). However, as expected, the single-level arthrodesis and two-level hybrid treatment groups demonstrated a decreased ROM at C6-C7 versus the intact spine and arthroplasty treatments (p<.05). In terms of adjacent-level effects, two-level arthrodesis (C5-C7) led to increased ROM in the inferior level (C7-T1) in axial rotation and flexion extension compared with the intact spine and all other treatment groups (p<0.05). Lateral bending loading conditions demonstrated no significant difference among the treatment groups (p>.05). In flexion-extension, the centers of intervertebral rotation for the intact spine and single-level arthroplasty groups were localized in the central to posterior one-third of the inferior vertebral body for each motion segment: C5-C6, C6-C7, and C7-T1. The single-level arthrodesis group produced more diffuse centers of rotation, particularly at the operative (C6-C7) and inferior adjacent levels (C7-T1). CONCLUSIONS: This study highlights the biomechanical effects of single- and two-level cervical arthroplasty versus single- and two-level arthrodesis on four functional spinal levels (C4-T1). Operative-level ROM was preserved with single- and two-level arthroplasty under all loading modes. The distal adjacent level (C7-T1) demonstrated the greatest increase among the four levels in ROM compared with the intact condition after two-level arthrodesis. These kinematic findings were corroborated by changes in the adjacent-level centers of rotation after arthrodesis and may suggest a biomechanical cause of adjacent-level disease secondary to cervical arthrodesis. PMID- 20362253 TI - Quality of information concerning cervical disc herniation on the Internet. AB - BACKGROUND CONTEXT: Many Americans seek and are influenced in their decision making by medical information on the Internet. Past studies have repeatedly found information on most medical Web sites to be deficient and of low quality. Physicians must remain aware of the quality and reliability of the information available on the Internet for patient education purposes. PURPOSE: To assess quality and authorship of Internet Web sites regarding a common cervical spine disorder, cervical disc herniation. STUDY DESIGN: The present study is a systematic quality assessment survey of Web sites concerning cervical disc herniation. METHODS: Fifty relevant and unique sites were identified. The five most popular search engines were used to identify 100 Web sites using the search term, "cervical disc herniation." Using a validated technique, three orthopedic surgeons independently generated content quality scores and accuracy scores, then integrated into a single final total summary score for each Web site. RESULTS: Four of the five identified top-scoring Web sites were found to be commercial and one was academic. Most of the Web sites were found to be physician sponsored, followed by academic and commercial. CONCLUSIONS: There is wide variability in Web site quality, with most of the Web sites failing to be sufficiently comprehensive and accurate. Physicians treating patients with cervical disc herniation must remain vigilant in guiding their patients to proper information on the Internet. PMID- 20362254 TI - Posterior spinal interspinous arthrodesis L4-S1 with two bone sticks harvested from the tibias. Good outcome at the 13-year follow-up. PMID- 20362255 TI - Re: "prospective, randomized multicenter Food and Drug Administration investigational device exemption study of lumbar tool disc replacement with the CHARITE artificial disc versus lumbar fusion: five-year follow-up". PMID- 20362257 TI - Re: short applications of very low-magnitude vibrations attenuate expansion of the intervertebral disc during extended bed rest. PMID- 20362259 TI - The possibility of the impossible: miracles, wonder, and Thomas Jefferson's razor. PMID- 20362260 TI - William Segal: attending artist-attending physician? PMID- 20362261 TI - On Plugged in: at what price? PMID- 20362262 TI - On Is life a statin deficiency state? PMID- 20362264 TI - Trends that will affect your future...: nonlocal linkage and the social dimension. AB - The SchwartzReport tracks emerging trends that will affect the world, particularly the United States. For EXPLORE, it focuses on matters of health in the broadest sense of that term, including medical issues, changes in the biosphere, technology, and policy considerations, all of which will shape our culture and our lives. PMID- 20362265 TI - The antioxidant debate. PMID- 20362266 TI - Health and medical economics applied to integrative medicine. AB - Cost-benefit analyses (CBA) of every aspect of health and medical care are a necessity to address both the clinical effectiveness and cost effectiveness of health and medical care for the purpose of allocating limited practitioner, organizational, governmental, and monetary resources while maintaining the highest quality outcomes. In response, there are an array of approaches that emphasize the full continuum of prevention, restructuring primary care, involvement of the workplace and communities, and adoption of innovative strategies and interventions ranging from genomic assessments to complementary and alternative medicine (CAM). Among these approaches is an integrative medicine (IM) model that is consistent with these national objectives and that uniquely and explicitly includes "evidence-based global medical strategies" in its definition. All of these strategies require rigorous, appropriate, state-of-the art medical economic analyses. Since few if any IM models have been rigorously evaluated in terms of CBA, it is possible to draw upon the cost-effectiveness research focused on a limited number of CAM modalities as well as from the work site/corporate clinical and cost outcomes research to suggest the evidence-based foundation from which a true healthcare system will evolve. PMID- 20362267 TI - Radial artery hemodynamic changes related to acupuncture. AB - BACKGROUND: Assessment of the radial pulse by palpation (pulse diagnosis) is an important diagnostic technique in Traditional Chinese Medicine (TCM), but the changes of blood flow volume in the radial artery during and after acupuncture are unknown. OBJECTIVE: The aim of this study was to explore the changes of radial artery blood flow volume during and after acupuncture in healthy subjects. DESIGN: This study was conducted as a pilot study utilizing a one-group intervention design. SETTING: The study was conducted at a TCM outpatient clinic of Tohoku University Hospital. PARTICIPANTS: Twenty-six healthy volunteers participated in the study. INTERVENTION: Acupuncture was performed at LR-3 bilaterally with manual rotation of the needles. OUTCOME MEASURES: Blood pressure was measured at rest and 180 seconds after acupuncture. Radial artery hemodynamics were monitored continuously with a high-resolution ultrasound echo tracking system. The vessel diameter and blood flow volume of the right radial artery and heart rate were measured at rest, before acupuncture, during acupuncture, and 30, 60, and 180 seconds after acupuncture. RESULTS: The systolic and diastolic diameter of the radial artery did not significantly change. Radial artery blood flow volume decreased significantly during acupuncture (mean +/- SD, 0.16 +/- 0.11 mL/sec per m(2); P < .01) compared with baseline (0.43 +/- 0.27 mL/sec per m(2)), but was increased at 180 seconds after acupuncture (0.54 +/- 0.28 mL/sec per m(2); P < .01). CONCLUSIONS: The present study showed that radial artery blood flow volume decreased immediately during acupuncture at the LR-3 acupoint, but was increased at 180 seconds after acupuncture. PMID- 20362268 TI - The development of green care in western European countries. AB - This article represents a review of green care across Western European countries. The following questions are addressed: What is green care, and what are its basic goals? What are the most commonly known types of green care interventions, and how are they connected to each other? There are different sectors of green care intervention that vary from each other regarding their structure, specific goals, and purpose. These traits will be investigated in this review. And lastly, how these interventions are designed and their approach to promote and provide health will be examined. PMID- 20362269 TI - Teaching research literacy: a model faculty development program at Oregon College of Oriental Medicine. AB - Content on integrative healthcare and complementary and alternative medicine is being taught in hundreds of educational programs across the country. Nursing, medical, osteopathic, chiropractic, acupuncture, naturopathic, and other programs are finding creative and innovative ways to include these approaches in new models of education and practice. This column spotlights such innovations in integrative healthcare and CAM education and presents readers with specific educational interventions they can adapt into new or ongoing educational efforts at their institution or programs. We invite readers to submit brief descriptions of efforts in their institutions that reflect the creativity, diversity, and interdisciplinary nature of the field. Please submit to Dr Sierpina at vssierpi@utmb.edu or Dr Kreitzer at kreit003@umn.edu. Submissions should be no more than 500 to 1,500 words. Please include any Web site or other resource that is relevant, as well as contact information. PMID- 20362270 TI - Microscopic description of a drop on a solid surface. AB - Two approaches recently suggested for the treatment of macro- or nanodrops on smooth or rough, planar or curved, solid surfaces, based on fluid-fluid and fluid solid interaction potentials are reviewed. The first one employs the minimization of the total potential energy of a drop by assuming that the drop has a well defined profile and a constant liquid density in its entire volume with the exception of the monolayer nearest to the surface where the density has a different value. As a result, a differential equation for the drop profile as well as the necessary boundary conditions are derived which involve the parameters of the interaction potentials and do not contain such macroscopic characteristics as the surface tensions. As a consequence, the macroscopic and microscopic contact angles which the drop profile makes with the surface can be calculated. The macroscopic angle is obtained via the extrapolation of the circular part of the drop profile valid at some distance from the surface up to the solid surface. The microscopic angle is formed at the intersection of the real profile (which is not circular near the surface) with the surface. The theory provides a relation between these two angles. The ranges of the microscopic parameters of the interaction potentials for which (i) the drop can have any height (volume), (ii) the drop can have a restricted height but unrestricted volume, and (iii) a drop cannot be formed on the surface were identified. The theory was also extended to the description of a drop on a rough surface. The second approach is based on a nonlocal density functional theory (DFT), which accounts for the inhomogeneity of the liquid density and temperature effects, features which are missing in the first approach. Although the computational difficulties restrict its application to drops of only several nanometers, the theory can be applied indirectly to macrodrops by calculating the surface tensions and using the Young equation to determine the contact angle. Employing the canonical ensemble version of the DFT, nanodrops on smooth and rough solid surfaces could be investigated and their characteristics, such as the drop profile, contact angle, as well as the fluid density distribution inside the drop can be determined as functions of the parameters of the interaction potentials and temperature. It was found that the contact angle of the drop has a simple (quasi)universal dependence on the energy parameter epsilon(fs) of the fluid-solid interaction potential and temperature. The main feature of this dependence is the existence of a fixed value theta(0) of the contact angle theta which separates the solid substrates (characterized by the energy parameter epsilon(fs) of the fluid-solid interaction potential) into two classes with respect to their temperature dependence. For theta>theta(0) the contact angle monotonously increases and for theta 1.25, and in 0/7 with lower OR(PR). Statistically significant associations were detected in all analyses that were adequately powered. In each of the five diseases studied, at least one previously reported association was replicated. These data demonstrate that phenotypes representing clinical diagnoses can be extracted from EMR systems, and they support the use of DNA resources coupled to EMR systems as tools for rapid generation of large data sets required for replication of associations found in research cohorts and for discovery in genome science. PMID- 20362272 TI - Evidence for polygenic susceptibility to multiple sclerosis--the shape of things to come. AB - It is well established that the risk of developing multiple sclerosis is substantially increased in the relatives of affected individuals and that most of this increase is genetically determined. The observed pattern of familial recurrence risk has long suggested that multiple variants are involved, but it has proven difficult to identify individual risk variants and little has been established about the genetic architecture underlying susceptibility. By using data from two independent genome-wide association studies (GWAS), we demonstrate that a substantial proportion of the thousands of variants that individually fail to show statistically significant evidence of association have allele frequencies in cases that are skewed away from the null distribution through the effects of multiple as-yet-unidentified risk loci. The collective effect of 12,627 SNPs with Cochran-Mantel-Haenszel test (p < 0.2) in our discovery GWAS set optimally explains approximately 3% of the variance in MS risk in our independent target GWAS set, estimated by Nagelkerke's pseudo-R(2). This model has a highly significant fit (p = 9.90E-19). These results statistically demonstrate a polygenic component to MS susceptibility and suggest that the risk alleles identified to date represent just the tip of an iceberg of risk variants likely to include hundreds of modest effects and possibly thousands of very small effects. PMID- 20362273 TI - Previous estimates of mitochondrial DNA mutation level variance did not account for sampling error: comparing the mtDNA genetic bottleneck in mice and humans. AB - In cases of inherited pathogenic mitochondrial DNA (mtDNA) mutations, a mother and her offspring generally have large and seemingly random differences in the amount of mutated mtDNA that they carry. Comparisons of measured mtDNA mutation level variance values have become an important issue in determining the mechanisms that cause these large random shifts in mutation level. These variance measurements have been made with samples of quite modest size, which should be a source of concern because higher-order statistics, such as variance, are poorly estimated from small sample sizes. We have developed an analysis of the standard error of variance from a sample of size n, and we have defined error bars for variance measurements based on this standard error. We calculate variance error bars for several published sets of measurements of mtDNA mutation level variance and show how the addition of the error bars alters the interpretation of these experimental results. We compare variance measurements from human clinical data and from mouse models and show that the mutation level variance is clearly higher in the human data than it is in the mouse models at both the primary oocyte and offspring stages of inheritance. We discuss how the standard error of variance can be used in the design of experiments measuring mtDNA mutation level variance. Our results show that variance measurements based on fewer than 20 measurements are generally unreliable and ideally more than 50 measurements are required to reliably compare variances with less than a 2-fold difference. PMID- 20362274 TI - Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. AB - We investigated two male infant patients who were given a diagnosis of progressive mitochondrial encephalomyopathy on the basis of clinical, biochemical, and morphological features. These patients were born from monozygotic twin sisters and unrelated fathers, suggesting an X-linked trait. Fibroblasts from both showed reduction of respiratory chain (RC) cIII and cIV, but not of cI activities. We found a disease-segregating mutation in the X-linked AIFM1 gene, encoding the Apoptosis-Inducing Factor (AIF) mitochondrion-associated 1 precursor that deletes arginine 201 (R201 del). Under normal conditions, mature AIF is a FAD-dependent NADH oxidase of unknown function and is targeted to the mitochondrial intermembrane space (this form is called AIF(mit)). Upon apoptogenic stimuli, a soluble form (AIF(sol)) is released by proteolytic cleavage and migrates to the nucleus, where it induces "parthanatos," i.e., caspase-independent fragmentation of chromosomal DNA. In vitro, the AIF(R201 del) mutation decreases stability of both AIF(mit) and AIF(sol) and increases the AIF(sol) DNA binding affinity, a prerequisite for nuclear apoptosis. In AIF(R201 del) fibroblasts, staurosporine-induced parthanatos was markedly increased, whereas re-expression of AIF(wt) induced recovery of RC activities. Numerous TUNEL-positive, caspase 3-negative nuclei were visualized in patient #1's muscle, again indicating markedly increased parthanatos in the AIF(R201 del) critical tissues. We conclude that AIF(R201 del) is an unstable mutant variant associated with increased parthanatos-linked cell death. Our data suggest a role for AIF in RC integrity and mtDNA maintenance, at least in some tissues. Interestingly, riboflavin supplementation was associated with prolonged improvement of patient #1's neurological conditions, as well as correction of RC defects in mutant fibroblasts, suggesting that stabilization of the FAD binding in AIF(mit) is beneficial. PMID- 20362275 TI - Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. AB - Osteogenesis imperfecta is a clinically and genetically heterogeneous brittle bone disorder that results from defects in the synthesis, structure, or posttranslational modification of type I procollagen. Dominant forms of OI result from mutations in COL1A1 or COL1A2, which encode the chains of the type I procollagen heterotrimer. The mildest form of OI typically results from diminished synthesis of structurally normal type I procollagen, whereas moderately severe to lethal forms of OI usually result from structural defects in one of the type I procollagen chains. Recessively inherited OI, usually phenotypically severe, has recently been shown to result from defects in the prolyl-3-hydroxylase complex that lead to the absence of a single 3 hydroxyproline at residue 986 of the alpha1(I) triple helical domain. We studied a cohort of five consanguineous Turkish families, originating from the Black Sea region of Turkey, with moderately severe recessively inherited OI and identified a novel locus for OI on chromosome 17. In these families, and in a Mexican American family, homozygosity for mutations in FKBP10, which encodes FKBP65, a chaperone that participates in type I procollagen folding, was identified. Further, we determined that FKBP10 mutations affect type I procollagen secretion. These findings identify a previously unrecognized mechanism in the pathogenesis of OI. PMID- 20362276 TI - 5-Aza-2'-deoxycytidine treatment induces skeletal myogenic differentiation of mouse dental pulp stem cells. AB - OBJECTIVE: Tissue stem cells in dental pulp are assumed to possess differentiation potentials similar to mesenchymal stem cells (MSCs). The aim of this in vitro study is to examine the differentiation potentials of mouse dental pulp stem cells (DPSCs) and develop the appropriate differentiation assay systems for skeletal myogenic differentiation of these cells. METHODS: Dental pulps were extracted from mandible sections of C57/BL6 mice, and adherent dental pulp cells were isolated in culture. These cells were cultured in osteogenic or adipogenic induction medium to induce osteogenic and adipogenic differentiation. On the other hand, the skeletal myogenic differentiation potential of these cells was investigated using different conditions, such as serum-free medium, Myod1 overexpression, or 5-Aza-2'-deoxycytidine (5-Aza) treatment for DNA demethylation. Muscle-specific transcriptional factor expression was evaluated by RT-PCR, and myotube formation and myosin heavy chain expression were evaluated by phase-contrast microscopy and immunofluorescence staining, respectively. RESULTS: The adherent dental pulp cells exhibited a proliferative capacity and they showed osteogenic and adipogenic differentiation as seen in previous studies. Although the expression of Myod1 mRNA and myotube formation was not detected in serum-free conditions, the forced expression of Myod1 up-regulated the expression of Myogenin and Pax7 mRNA. However, myotube formation was not confirmed. Interestingly, myosin heavy chain expression and myotube formation were observed following 5-Aza treatment of these cells. CONCLUSIONS: These results demonstrated that mouse DPSCs possess MSC-like differentiation potential. DNA demethylation induced by 5-Aza treatment resulted in the skeletal muscle differentiation in mouse DPSCs, suggesting that DNA demethylation might trigger this differential induction of mouse DPSCs. PMID- 20362277 TI - Synthesis of the glycosylated polypeptide chain of an inducible costimulator on T cells. AB - The glycoprotein AILIM/ICOS (Activation inducible lymphocyte immunomediately molecule/Inducible co-stimulator) on T-cells was identified in 1998 as a member of the CD28/CTLA4 family. The three-dimensional structure of the AILIM/ICOS extracellular domain has not been solved, and therefore we have examined the preparation of homogeneous glycosylated polypeptide chains of this domain having two homogeneous N-linked complex type oligosaccharides for use in folding experiments. To synthesize the glycosylated whole polypeptide chain of the AILIM/ICOS extracellular domain, the target polypeptide chain was divided into four segments, each containing a cysteine residue. Those peptide segments were synthesized by conventional SPPS, followed by thioesterification of the C terminus. The oligosaccharide moiety, a biantennary complex type disialyloligosaccharide, was attached to the cysteine thiol in the peptide backbone using the haloacetamide method. These peptides, as well as a glycosylated peptide, were sequentially coupled by use of native chemical ligation. This process successfully afforded the desired polypeptide chain having homogeneous oligosaccharides. PMID- 20362278 TI - Immunostimulating effects of a sulfated galactan from Codium fragile. AB - A pyruvylated sulfated galactan from Codium fragile is a highly ramified polysaccharide consisting of 3-linked, 3,6-linked, and non-reducing terminal d galactose with pyruvate and sulfate groups; the glycan exerts anti-herpes simplex virus type 2 effects in vitro and in vivo. This particular polysaccharide was found to stimulate the production of nitric oxide by inducing iNOS at the mRNA and protein levels. In addition, the polysaccharide also induced several cytokine mRNA expressions such as IL-1beta, IL-6, IL-10 and TNF-alpha. Therefore, it appears that the sulfated galactan might possess the immunostimulating effects via activation of macrophages. PMID- 20362279 TI - Inhibiting effects of total saponins of panax ginseng on immune maturation of dendritic cells induced by oxidized-low density lipoprotein. AB - Total saponins of panax ginseng (TSPG) are the major active components in panax ginseng. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TSPG on the maturation and immune function of DCs. Compared with those untreated, the DCs pre-treated with TSPG and then induced by oxidized-LDL exhibited a significantly lower expression of the maturation associated markers of CD40, CD86, HLA-DR, and CD1a, together with an increased endocytosic function as well as decreased secretions of cytokine. However, silencing the expression of PPARgamma in DCs, the inhibitory effect of TSPG on the maturation DCs was significantly reduced. In conclusion, TSPG could inhibit the maturation of DCs induced by oxidized-LDL which suggests beneficial effects on atherosclerosis and this effect was partly dependent on the PPARgamma pathway at least. PMID- 20362280 TI - [Hypercalcemic crisis as first manifestation of primary hyperparathyroidism in adolescence]. PMID- 20362281 TI - Functional studies of acid transporter in cultured rat epididymal cell. AB - OBJECTIVE: To explore the functional role of vacuolar H(+)-ATPase in the pH regulation of epididymal fluid and its effect on sperm motility. DESIGN: Experimental study. SETTING: Physiology laboratory in a university. ANIMAL(S): Immature male Sprague-Dawley rats. INTERVENTION(S): The H(+)-ATPase inhibitor was applied to the primary culture of epididymal cells. MAIN OUTCOME MEASURE(S): The intracellular luminal fluid pH and sperm percent motility were recorded. RESULT(S): Double immunofluorescence of H(+)-ATPase and carbonic anhydrase II in primary culture of cauda epididymal epithelial cells showed that the system was a suitable model for investigation of acid secretion by clear cells. Clear cells were pharmacologically distinct from principal cells in acid/base transportation. The intracellular pH recovery from cellular acidification was suppressed by the H(+)-ATPase inhibitor bafilomycin A1(100 nM) and the Na(+)/H(+) exchanger inhibitor amiloride (1 mM) by 85% and 54%, respectively. These results suggest that, in addition to Na(+)/H(+) exchanger, clear cells actively pump proton from cytoplasm into extracellular space through H(+)-ATPase. In addition, inhibition of H(+)-ATPase by bafilomycin A1 blocked the acidification of luminal fluid with IC(50) values of 12 nM, which supports that H(+)-ATPase acidifies the luminal fluid. We also confirm that the acid fluid regulates rat cauda sperm motility. CONCLUSION(S): The present work shows that clear cells, the minority cell type of epididymal cell population, play an important role in the pH regulation of epididymal fluid by H(+)-ATPase. PMID- 20362282 TI - A rare case report: ovarian heterotopic pregnancy after in vitro fertilization. AB - OBJECTIVE: To report a case of ovarian heterotopic pregnancy after an IVF cycle. DESIGN: Case report. SETTING: Reproductive medicine unit, Christian Medical College Hospital, Vellore, India. PATIENT(S): A woman with an ovarian heterotopic pregnancy. INTERVENTION(S): Laparoscopic removal of ovarian ectopic pregnancy. MAIN OUTCOME MEASURE(S): Early detection and successful treatment of heterotopic pregnancy. RESULT(S): Successful laparoscopic management of ovarian pregnancy resulting in a single viable ongoing intrauterine pregnancy. CONCLUSION(S): Clinicians need to be aware of such rare and potentially fatal presentations after IVF, because early diagnosis and management in these cases can yield a favorable outcome. PMID- 20362283 TI - Use of F 18-fluoro-D-glucose-positron emission tomography-computed tomography to localize a hilar cell tumor of the ovary. AB - OBJECTIVE: To describe provocative testing and alternative imaging strategies used to localize an androgen-producing tumor in a 58-year-old woman with severe hirsutism. DESIGN: Case report. SETTING: Clinical Research Center. PATIENT(S): A 58-year-old woman who was seen for evaluation of severe hirsutism. INTERVENTION(S): Serum androgen levels were measured at baseline, 4 hours after administration of 2000 IU of hCG, and 11 days after administration of 3.75 mg of leuprolide acetate (LA). Magnetic resonance imaging and F 18-fluoro-D-glucose positron emission tomography-computed tomography (FDG-PET/CT) were performed. MAIN OUTCOME MEASURE(S): Description of preoperative provocative testing and imaging. RESULT(S): In response to hCG, T rose from 243 to 288 ng/dL then decreased to 233 ng/dL after LA administration. The FDG-PET/CT scan demonstrated focal hypermetabolism in the right pelvis, corresponding to a soft-tissue density on the noncontrast CT scan. Magnetic resonance images were correlated with the PET/CT, and the right ovary was identified. Right salpingo-oophorectomy was performed, and final pathologic examination revealed a hilar cell tumor with ovarian cortical hyperplasia. CONCLUSION(S): This case demonstrates the utility of provocative testing in the evaluation of a patient with severe hirsutism and illustrates the value of FDG-PET/CT when traditional imaging is nondiagnostic. PMID- 20362284 TI - EUS-guided fiducial placement for stereotactic body radiotherapy in locally advanced and recurrent pancreatic cancer. AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) has been approved for the treatment of locally advanced pancreatic cancer. Placement of gold fiducials is required for real-time tracking and delivery of a high-dose therapeutic beam of radiation to the tumor. Traditionally, fiducials have been placed either intraoperatively or percutaneously. Recently, EUS-guided fiducial placement has been reported, but the safety and feasibility of this approach is not well defined. OBJECTIVE: The aim of this study was to determine the safety, feasibility, and limitations of EUS-guided placement of 0.8 x 5.0 mm fiducials via a 19-gauge needle for locally advanced and recurrent pancreatic cancer. DESIGN: Prospective study of patients with either locally advanced or recurrent pancreatic cancer referred for EUS-guided fiducial placement for SBRT at our institution over a 3-year period. SETTING: Tertiary referral center conducting >1800 EUS procedures annually. MAIN OUTCOME MEASUREMENTS: Primary outcome measurements included success, complications, and technical limitations of EUS guided fiducial placement in pancreatic cancer. In addition, the percentage of patients successfully completing SBRT after EUS-guided fiducial placement was determined. RESULTS: A total of 51 patients (mean age 73 years; 57% male) with locally advanced (n = 36) and recurrent (n = 15) pancreatic cancer were referred for EUS-guided fiducial placement. Fiducials were successfully placed in 46 patients (90%), with technical failures occurring in 4 patients (8%) with recurrent cancer after pancreaticoduodenectomy. In 3 patients (7%), the fiducials spontaneously migrated from the original site of injection, thereby requiring a second EUS procedure for placement of additional fiducials. Of the 46 patients with fiducials placed under EUS guidance, 42 patients (91%) successfully completed SBRT. Two patients experienced disease progression before SBRT, 1 patient was lost to follow-up, and 1 patient experienced a complication at ERCP that precluded further therapy. Only 1 complication (2%), of mild pancreatitis, occurred in a patient undergoing simultaneous placement of fiducials and celiac plexus neurolysis for intractable abdominal pain. LIMITATIONS: Single-center experience and lack of a formal follow-up protocol to assess for complications. CONCLUSION: EUS-guided fiducial placement for SBRT in locally advanced and recurrent pancreatic cancer is safe and feasible. Successful placement was achieved in 90% of patients, with a low complication rate (2%). Furthermore, 91% of patients successfully completed SBRT after EUS-guided fiducial delivery. Although fiducials can spontaneously migrate from the initial injection site, the rate of migration is relatively low (7%), and no migration-related complications occurred over the course of this study. Limitations to EUS-guided fiducial placement may include surgically altered anatomy (pancreaticoduodenectomy) in patients with recurrent pancreatic cancer. PMID- 20362285 TI - The safety and probable therapeutic effect of routine use of antibiotics and simultaneously treating bleeding gastric varices by using endoscopic cyanoacrylate injection and concomitant esophageal varices with banding ligation: a pilot study. AB - BACKGROUND: Gastroesophageal varices are the most common type of gastric varices. Although endoscopic injection of N-butyl-2-cyanoacrylate is the current treatment of choice for acute gastric variceal bleeding, whether the concomitant esophageal varices should be ligated simultaneously with the first treatment session is currently not known. OBJECTIVE: The aim of this study was to evaluate the safety and probable therapeutic effect of simultaneous cyanoacrylate injection for bleeding gastric varices obliteration (GVO) and endoscopic band ligation (EBL) for concomitant esophageal varices in combination with routine antibiotics (simultaneous group), and to compare our results with historical results in which the patients underwent GVO first and then EBL for concomitant esophageal varices (separate group). DESIGN: A single-center pilot study. SETTING: A tertiary referral center. PATIENTS: Patients with liver cirrhosis and gastroesophageal varices, who presented with acute gastric varices bleeding. INTERVENTIONS: Simultaneous treatment in the form of GVO and EBL for concomitant esophageal varices in combination with routine antibiotics. MAIN OUTCOME MEASUREMENT: Rebleeding and mortality within the first year of index bleeding. RESULTS: Twenty patients in the simultaneous group and 67 patients in the separate group were included in the study. The 2 groups had similar baseline characteristics. The hemostasis of active bleeding was 100% in both groups (7/7 vs 20/20). The 1-year rebleeding rate was 10% (2/20) in the simultaneous group and 37.31% (25/67) in the separate group (P = .041). Kaplan-Meier analysis showed higher probability of remaining free of rebleeding in the simultaneous group (88.5% vs 61.1%; P = .044). Multivariate analysis indicated that treatment method (separate group) and high model for end-stage liver disease score (> or = 13) were independent risk factors of rebleeding in 1 year. The treatment failure, complications, 1-year mortality, and survival were similar in both groups. CONCLUSION: Simultaneous endoscopic treatment for gastric varices bleeding and concomitant esophageal varices is a safe and effective procedure in combination with antibiotic prophylaxis for patients with cirrhosis. The 1-year mortality rate was similar between the 2 groups. The results need further validation. PMID- 20362286 TI - Patients' description of rectal effluent and quality of bowel preparation at colonoscopy. AB - BACKGROUND: There are few data evaluating how accurately patients can predict the quality of their colonoscopy preparation. OBJECTIVE: The aim of this study was to assess whether patients' description of rectal effluent predicts preparation quality as assessed per endoscopist. DESIGN: Prospective, cross-sectional. SETTING: Three outpatient endoscopy units at Indiana University Medical Center. PATIENTS: Patients undergoing colonoscopy were enrolled. INTERVENTIONS: Patients were given a questionnaire assessing their preparation based on the description of their last rectal effluent. This was compared with endoscopists assessment of preparation. MAIN OUTCOME MEASUREMENTS: Correlation between the patient's description of the last effluent and endoscopist's assessment of preparation. RESULTS: Of the total 429 patients, 59% were male and 75% were white. There was only slight agreement between the patients' description of effluent and the endoscopists' description of preparation (Cohen kappa statistic, 0.067). However, patients reporting brown liquid or solid had a 54% chance of having fair or poor preparation. Ingestion of <90% of the preparation, male gender, use of medications associated with constipation, and comorbid conditions were independent predictors of fair or poor preparation. LIMITATIONS: No validated system to assess the quality of the bowel preparation or for patients to assess their preparation. CONCLUSION: Patients' description of last rectal effluent is not a reliable predictor of quality of preparation per the endoscopist, but patients reporting their last effluent as brown liquid or solid have a substantial likelihood of inadequate preparation. These patients may benefit from additional preparation, which may be particularly useful if it can be administered in the endoscopy unit followed by colonoscopy on the same day. PMID- 20362287 TI - Is pre-hospital thoracotomy necessary in the military environment? AB - INTRODUCTION: Exsanguination from penetrating torso injury is a major source of mortality on the battlefield. Advanced Life Support guidelines suggest 'on-scene' thoracotomy for patients in cardiac arrest following penetrating chest trauma. This requires significant resourcing and training. Experience from published series (31 pre-hospital thoracotomies with 3 survivors) suggests that when this manoeuvre is applied to a well selected group it is a significant and life-saving procedure. Can this be applied to military injuries? METHODS: Over a 12 month period on Operation Herrick all patients who sustained significant thoracic trauma were retrospectively reviewed. Parameters were recorded to allow detailed analysis of injury pattern and operative management. Our main objective was to determine if an early (pre-hospital) thoracotomy would have influenced the outcome. RESULTS: Over the period, 81 patients required operative intervention following thoracic trauma: 8 patients underwent emergency thoracotomy (performed as part of the resuscitation) and 14 underwent urgent thoracotomy (performed after physiology partly restored). There were 9 fatalities--7 undergoing emergency thoracotomy and 2 post-operatively from multi-organ failure. Of the 7 intra-operative deaths 4/7 patients had thoracic injury and 6/7 had additional abdominal injuries. The median predicted survival of fatalities was 2.0% using Trauma Injury Severity Scoring. DISCUSSION: Emergency thoracotomy should be performed in cardiac arrest following penetrating trauma as soon as possible. Highest survival rates in both in-hospital and pre-hospital thoracotomy are found in isolated cardiac stab wounds (19.4%). Poorest survival is found in multiply, ballistic injured patients (0.7%). The latter best reflects the injury pattern of military patients who have cardiac arrest following penetrating torso injury. CONCLUSION: As our injury pattern suggests, any pre-hospital thoracotomy on military patients is likely to require complex intervention in very challenging environments. Our evidence does not support the notion that earlier thoracotomy could improve survival. PMID- 20362288 TI - Risk factors for vaginal prolapse after hysterectomy. AB - OBJECTIVE: To identify risk factors for pelvic organ prolapse (POP) and their influence on the occurrence of vaginal prolapse after hysterectomy. METHODS: Medical records from 2 groups of women who had undergone hysterectomy were reviewed retrospectively. The study group was 82 women who had undergone surgery for vaginal prolapse after hysterectomy; the control group was 124 women who had undergone hysterectomy with no diagnosis of vaginal prolapse by the time of the study. All hysterectomy procedures had been performed for benign gynecological disease, including POP. Both groups of women completed a self-administered questionnaire to obtain additional information on the occurrence of POP. RESULTS: The incidence of vaginal prolapse after hysterectomy was significantly higher in women with a higher number of vaginal deliveries, more difficult deliveries, fewer cesareans, complications after hysterectomy, heavy physical work, neurological disease, hysterectomy for pelvic organ prolapse, and/or a family history of pelvic organ prolapse. Premenopausal women had vaginal prolapse corrected an average of 16 years after hysterectomy, and postmenopausal women 7 years post hysterectomy. CONCLUSION: Before deciding on hysterectomy as the approach to treat a woman with pelvic floor dysfunction, the surgeon should evaluate these risk factors and discuss them with the patient. PMID- 20362289 TI - Tumor lysis syndrome associated with carboplatin and paclitaxel in a woman with recurrent endometrial cancer. PMID- 20362290 TI - Assessment of carotid plaque echolucency in addition to plaque size increases the predictive value of carotid ultrasound for coronary events in patients with coronary artery disease and mild carotid atherosclerosis. AB - OBJECTIVES: This study examined whether combined ultrasound assessment of plaque size and echolucency in the carotid artery had an additive effect for predicting coronary events in patients with coronary artery disease (CAD). Ultrasound assessment of either plaque size or echolucency of carotid artery provides prognostic information on coronary events. Combined assessment of plaque size and echolucency of carotid artery has the advantage of obtaining both structural and compositional information in the same artery in a single session. METHODS AND RESULTS: Ultrasound assessment of carotid plaque maximum intima-media thickness (plaque-IMTmax) and echolucency with integrated backscatter analysis was performed in 413 patients with CAD and carotid plaque. All study patients were followed up prospectively for 54 months or until the occurrence of a coronary event. During the follow-up period, 49 coronary events occurred including 2 cardiac deaths, 10 non-fatal acute myocardial infarctions and 37 recurrent and refractory unstable angina. Multivariate Cox hazards analysis showed plaque IMTmax alone (HR 2.01, 95%CI 1.30-3.10), plaque echogenicity alone (HR 0.86, 95%CI 0.80-0.91) and combination of high plaque-IMTmax and low echogenicity on categorical data (HR 2.56, 95%CI 1.39-4.74) were independent predictors of coronary events. Analysis using c-statistics showed that plaque-IMTmax and plaque echolucency in combination had a significant incremental effect on the predictive value of the conventional risk factors for coronary events. CONCLUSIONS: Combined ultrasound assessment of carotid plaque size and echolucency has an additive value for prediction of coronary events. Further studies need to evaluate the clinical utility of both ultrasound measurements for risk stratification in CAD. PMID- 20362291 TI - Never too late: a commentary on "Impact of age, sex and exercise on brachial and popliteal artery remodelling in humans". PMID- 20362292 TI - Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice. AB - OBJECTIVE: T and B lymphocytes are associated with atherosclerosis and aneurysms. Angiotensin II (AngII) infusion into hypercholesterolemic mice results in augmentation of atherosclerosis and abdominal aortic aneurysm (AAA) formation. In this study, we determined whether total lymphocyte deficiency reduced AngII induced vascular diseases. METHODS AND RESULTS: ApoE deficient (apoE -/-) mice were cross-bred with recombination activating gene-1 (Rag-1) deficient mice that lack mature T and B lymphocytes. Heterozygous littermates (Rag-1 +/-) have normal lymphocytic function and served as controls. Male and female apoE -/- mice that were either Rag-1 +/- or -/- were fed a normal laboratory diet and infused with either saline or AngII (1000ng/kg/min) subcutaneously via osmotic mini pump for 28 days. Total lymphocyte deficiency had no significant effect on body weight and systolic blood pressure prior to and during AngII infusion. However, it was associated with decreased serum cholesterol concentrations. AngII infusion increased atherosclerotic lesion area in Rag-1 +/- mice compared to saline (P=0.017 in males and P=0.004 in females). This effect was significantly blunted in Rag-1 -/- male (P=0.044), but not female mice. AngII-infusion promoted increased width of the abdominal aorta, with a greater effect in males. Despite the reduction in atherosclerosis in males, Rag-1 deficiency had no significant effect on AngII-induced aortic dilation in either gender. CONCLUSION: T and B lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not AAA formation in apoE -/- mice. PMID- 20362293 TI - High levels of soluble intercellular adhesion molecule-1, insulin resistance and saturated fatty acids are associated with endothelial dysfunction in healthy adolescents. AB - OBJECTIVE: Atherosclerosis begins and progresses during childhood and adolescence. Endothelial dysfunction is one of the earliest abnormalities that can be detected in the development of atherosclerosis. As the determinants of endothelial function in childhood are unknown, we investigated the influence of cardiovascular risk factors on endothelial function in a cohort of healthy adolescents. METHODS: A total of 257 adolescents (age: 14.5 + or - 1.0 years, 138 girls) participated in this study. Endothelial function was measured as reactive hyperemic index (RHI) using a fingertip peripheral arterial tonometry device. Blood samples were collected for analysis of lipids, insulin, glucose, fatty acid composition of plasma phospholipids, and markers of inflammation and endothelial function. RESULTS: There was no gender difference in RHI. Boys had higher plasma level of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin and monocyte chemoattractant protein-1, and lower level of insulin, total cholesterol, high-density lipoprotein-cholesterol (HDL), low-density lipoprotein-cholesterol (LDL), ApoA1, ApoB, and docosahexaenoic acid of plasma phospholipids than girls. There was no gender difference regarding triacylglycerol, triacylglycerol/HDL, LDL/HDL and ApoB/ApoA. The RHI was inversely associated with plasma ICAM-1 (p=0.0003), HOMA index for insulin resistance (HOMA-IR, p=0.001) and saturated fatty acids of plasma phospholipids (SFA, p=0.001). The associations remained significant after adjusting for age, height, BMI-z-score, sex, blood pressure, HDL and smoking. CONCLUSION: In healthy adolescents impaired endothelial function is significantly associated with high level of soluble ICAM-1, HOMA-IR and SFA. PMID- 20362294 TI - Counter-current chromatographic separation of nucleic acid constituents with a hydrophilic solvent system. AB - Nucleic acid constituents such as nucleobases, nucleosides and nucleotides were separated by counter-current chromatography using type J coil planet centrifuge. The separation was performed with a hydrophilic solvent system composed of 1 propanol/800 mM potassium phosphate buffer (pH 7.4) (1:1, v/v) by eluting the lower aqueous phase at a flow-rate of 0.5 ml/min. Eight selected nucleic acid constituents (4.0 mg, 0.5 mg of each), uridine monophosphate (UMP), adenosine monophosphate (AMP), deoxyadenosine monophosphate (dAMP), uridine, urasile, deoxy uridine, adenosine and adenine were well resolved within 160 min. PMID- 20362295 TI - Multi-residue analysis of pharmaceutical compounds in wastewaters by dual solid phase microextraction coupled to liquid chromatography electrospray ionization ion trap mass spectrometry. AB - The aim of this article is to present a new procedure based on dual solid-phase microextraction (dSPME) for the simultaneous extraction of 16 pharmaceutical compounds with acidic and basic characteristics in urban wastewaters. Water samples are divided into two aliquots of 2 mL each extracted by two CW-TPR fibers at different pH values (pH 3 and 11) and with a NaCl concentration of 300 g L(-1) at 75 degrees C for 30 min. The analytes in both fibers are desorbed one after the other in the desorption chamber in static mode with mobile phase for 10 min. The extracts are injected into an LC system coupled to an ion trap mass spectrometer, leading to the accurate quantification of 16 pharmaceutical compounds in wastewaters, in MS(2) mode. All the target compounds found in wastewaters provide good signals corresponding to the protonated precursor ion [M+H](+). The parameters influencing adsorption and desorption of the analytes on fiber were optimized. The assessment of the analytical method was performed by studying the linearity (LOQ to 10 ng mL(-1)) and the intra- and interday accuracy (89.2-109.7%) and precision (RSD <13.6%). The quantification limits obtained ranged between 0.005 and 0.05 microg L(-1). The application of the method to real samples proves its effectiveness in identifying and detecting naproxen, valsartan, bezafibrate, torasemide, diclofenac, carbamazepine, citalopram, lorazepan, fluoxetine, imipramine and amitriptyline in influent and effluent wastewater treatment plant samples. PMID- 20362296 TI - Interaction of bovine serum albumin with gemini surfactants. AB - The interactions between bovine serum albumin and cationic gemini surfactants were investigated as a function of concentration, under different pH conditions. The investigation deals with dielectric relaxation, dynamic light scattering, zeta-potential, circular dichroism, and UV spectroscopy. The interactive behavior of the anionic form is quite different from the cationic species. It indicates that protein-surfactant interactions are mostly electrostatic in nature and depend on the state of charge of bovine serum albumin. The results indicate the presence of both hydrophobic and electrostatic contributions in the interactions of gemini with bovine serum albumin. Comparison of dynamic light scattering, dielectric relaxation, electrophoretic mobility, and optical circular dichroism allows drawing some preliminary hypotheses on the different contributions to surfactant binding and supports former studies on the formation of complexes between the bovine serum albumin and the above species. PMID- 20362297 TI - Evaluation of removal efficiency of fluoride from aqueous solution using new charcoals that contain calcium compounds. AB - Charcoals that contain calcium compounds have been synthesized by impregnating wood with calcium chloride followed by carbonization at 500 degrees C, 650 degrees C or 900 degrees C. The charcoals were characterized by SEM, EDAX, XRD and chemical titrations. These adsorbents were porous with the wood microstructure. XRD revealed the presence of crystallized CaCO(3) and CaO. Despite this content, all the charcoals showed acidic surface properties and pH of point of zero charge (pH(PZC)) values were around 7.4-7.7. Their performance for fluoride removal from aqueous solution was evaluated by batch experiments. Fluoride adsorption kinetic followed a pseudo-second order model. Charcoal prepared at 650 degrees C exhibited the best efficiency with a fluoride sorption capacity of 19.05 mg g(-1) calculated from the Langmuir model. A fluoride residual concentration of 0.67 mg L(-1) was achieved within 24 h from a 10 mg L( 1) solution at neutral pH. The fluoride removal was not modified by the presence of NO(3)(-), SO(4)(2-) and PO(4)(3-) in the fluoride solution, while HCO(3)(-) and Cl(-) slightly affected the defluoridation capacity. The charcoals were chemically stable in solution and the amount of dissolved Ca was found to be 3.23 mg L(-1) at neutral pH. PMID- 20362298 TI - Mechanical and wettable behavior of polyacrylonitrile reinforced fibrous polystyrene mats. AB - In this study, we have fabricated the polyacrylonitrile (PAN) reinforced super hydrophobic fibrous polystyrene (PS) mats via a multi-syringe electrospinning technique. The composition ratio of PS/PAN in the blend mats could be controlled by tuning the number ratios of syringes of PS/PAN. The water contact angles (WCAs) of resultant fibrous mats was decreased from 155 degrees to 143 degrees with the decreasing the number ratios of syringes of PS/PAN from 4/0 to 1/3. The addition of the component of PAN nanofibers in fibrous PS mats significantly improved the mechanical properties of PS mats. At a critical syringe ratio of 3/1 (PS/PAN), the mat surface showed a WCA of 150 degrees with a three times increased tensile strength compared with the pure PS mats. Additionally, the results of field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR), and mechanical properties indicated the multi-syringe electrospinning technique is an effective approach to fabricate the large-scale well-dispersed blend fibrous mats. PMID- 20362299 TI - Enzymatic proteolysis of alpha gliadin monolayer spread at the air-water interface. AB - The mechanism of the enzymatic hydrolysis under the proteolytic enzyme action of a plant protein alpha gliadin organized as a model monolayer system at the air/water interface was studied. The advantage of the monolayer technique is the ability to control and modify easily the interfacial organization of the molecules and the possibility to optimize the conditions for the hydrolysis. Enzymatic hydrolysis was studied by using a traditional barostat surface balance. The hydrolysis kinetic was followed by measuring simultaneously the decrease of the surface area and change of the surface potential with time. The decrease with time in film area is result of the random scission of the peptide bonds of polypeptide chain and their solubilization in the aqueous subphase. The interpretation of the surface potential data is based on the contribution of the dipole moments of the intact and broken peptide groups. An appropriate kinetic model describing the proteolytic action of a peptidase was applied and the global kinetic constant was obtained. The random scission of the protein chains gave kinetic constants comparable with those measured during the hydrolytic scission of polyester macromolecules but quite different to the values obtained with short chain lipids. PMID- 20362300 TI - Increasing incidence of kidney stones in children evaluated in the emergency department. AB - OBJECTIVE: To test the hypothesis that there is an increase in the incidence of childhood nephrolithiasis in the state of South Carolina. STUDY DESIGN: We analyzed demographic data from a statewide database on incidence of kidney stones from emergency department data and financial charges. Data were compared with population data from the US Census to control for population growth. RESULTS: There was a significant increase in the incidence of kidney stones in children between 1996 and 2007. The greatest rate of increase was seen in adolescents, pre adolescents, and Caucasian children. Infants, toddlers, and African-American children did not show significantly increased incidence in the period. Girls show a growing predominance in our population. The amount of money charged for care of children with kidney stones has gone up >4-fold in our state. CONCLUSION: The incidence of kidney stone disease has risen dramatically in the state of South Carolina since 1996. Further studies investigating potential contributing factors are needed to prevent this costly and painful condition. PMID- 20362301 TI - Food selectivity in children with autism spectrum disorders and typically developing children. AB - OBJECTIVES: To define food selectivity and compare indices of food selectivity among children with autism spectrum disorders (ASDs) and typically developing children, and to assess the impact of food selectivity on nutrient adequacy. STUDY DESIGN: Food selectivity was operationalized to include food refusal, limited food repertoire, and high-frequency single food intake using a modified food frequency questionnaire and a 3-day food record. Food selectivity was compared between 53 children with ASDs and 58 typically developing children age 3 11 years. Nutrient adequacy was assessed relative to the dietary reference intakes. RESULTS: The children with ASDs exhibited more food refusal than typically developing children (41.7% of foods offered vs 18.9% of foods offered; P <.0001). They also had a more limited food repertoire (19.0 foods vs 22.5 foods; P <.001). Only 4 children with ASDs and 1 typically developing child demonstrated high-frequency single food intake. Children with a more limited food repertoire had inadequate intake of a greater number of nutrients. CONCLUSIONS: Our findings suggest that food selectivity is more common in children with ASDs than in typically developing children, and that a limited food repertoire may be associated with nutrient inadequacies. PMID- 20362302 TI - Outcome of dengue hemorrhagic fever-caused acute kidney injury in Thai children. AB - OBJECTIVES: To examine the outcome of acute kidney injury (AKI) in children with dengue hemorrhagic fever (DHF), the cause(s) of AKI, and the risk of AKI and fatality. STUDY DESIGN: The medical records of patients age <15 years during 1989 to 2007 were reviewed. DHF-caused AKI and patients with DHF with no AKI were matched 1:2 by age. RESULTS: DHF-caused AKI was clinically estimated to be 0.9% (25/2893) of admissions, with a high mortality rate of 64.0%. Risk factors of AKI were DHF grade IV and obesity (odds ratio, 16.9; 95% CI, 4.2 to 68.5, and odds ratio, 6.3; 95% CI, 1.4 to 28.8, respectively). Respiratory failure, hepatic failure, and massive bleeding were complications found in 80.0%, 96.0%, and 84.0% of cases with AKI, respectively. Fatality was more likely in cases with DHF grade IV, oliguric AKI, respiratory failure, or prolongation of prothrombin or activated partial thromboplastin time more than twice that of reference specimens. Among the survivors, none had chronic kidney disease, and serum creatinine levels returned to normal in 32 (1 to 48) days. CONCLUSIONS: Patients with DHF and AKI had a high mortality rate, although those who survived had a full return to normal function within 1 month. DHF grade IV and obesity were the major risk factors of AKI. PMID- 20362303 TI - Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. AB - Fibroblast growth factor-21 (FGF-21) has been proposed as a novel metabolic regulator, and animal experiments suggested that FGF-21 may affect energy balance. In humans, FGF-21 was correlated with obesity. Until now, no data exist regarding the relationship of FGF-21 and weight reduction in humans. We therefore investigated whether FGF-21 is modified by a moderate intended weight loss in a human trial. Thirty obese individuals (24 female, 6 male) participated in a weight reduction program for 6 months. In addition to several anthropometric and metabolic parameters, FGF-21 was measured before and after weight loss. Baseline serum FGF-21 was independently associated with markers of lipid metabolism and waist circumference. The multimodal intervention induced a moderate weight loss (97.4 +/- 3.1 vs 92.2 +/- 3.1 kg, P < .001), which was accompanied by a significant improvement of lipid and glucose metabolism. However, FGF-21 levels were not modified by moderate weight reduction; and FGF-21 levels at baseline were not a predictive marker for subsequent weight loss. The results presented here confirmed that FGF-21 levels are associated with markers of lipid metabolism and an estimate of abdominal adiposity. The finding that moderate weight loss did not induce changes of FGF-21 levels in humans suggests that FGF-21 is not directly regulated by fat mass under those conditions. PMID- 20362305 TI - [Imaging of orbital masses]. AB - A wide spectrum of tumors and pseudotumors may involve the orbit. Their clinical presentation is often nonspecific, consisting of exophthalmos, diplopia, visual loss, orbital pain or signs of orbital inflammation. Imaging plays a major role in the etiological diagnosis, providing a precise analysis of the location of the lesion, its components, and its effects on adjacent and nearby structures. It studies tumor extension and often provides a good evaluation of its composition. Imaging is mainly performed with MRI. CT is needed when the lesion affects the orbital walls. Ultrasound is proposed in case of anterior location of the mass or vascular lesion. This paper presents a brief summary of the technical aspects of imaging and of the normal anatomy of the orbit and its components. It presents the best sequences needed to depict specific pathologies and the aspects of the most common diseases encountered. PMID- 20362304 TI - Short-term adenosine monophosphate-activated protein kinase activator 5 aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle. AB - Adenosine monophosphate-activated protein kinase (AMPK) has been proposed to stimulate mitochondrial biogenesis and fat and glucose metabolism in skeletal muscle. Nicotinamide adenine dinucleotide-dependent histone deacetylase sirtuin 1 (SIRT1) is also thought to play a pivotal role for such metabolic adaptations. The purpose of the present study was to examine the effect of AMPK activation with the administration of AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D ribofuranoside (AICAR) to rats on skeletal muscle SIRT1 protein expression as well as peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC 1alpha) and glucose transporter 4 (GLUT4) protein expression and hexokinase activity. The AICAR promoted the phosphorylation of AMPK alpha-subunit (Thr172) and acetyl-coenzyme A carboxylase (Ser79) without any change of total AMPK alpha subunit or acetyl-coenzyme A carboxylase protein levels in both the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. The SIRT1 protein expression increased at 24 hours after administration of AICAR in the EDL muscle but not in the soleus muscle. The PGC-1alpha protein expression increased in both the soleus and EDL muscles and GLUT4 did in the EDL muscle at 24 hours after an administration of AICAR. The hexokinase activity increased at 18 and 24 hours in the soleus and at 12, 18, and 24 hours in the EDL after an AICAR treatment. These results suggest that short-term AICAR treatment to rats promotes skeletal muscle AMPK phosphorylation and then coincidently increases the SIRT1 protein expression. In addition, such treatment also enhances the PGC-1alpha and GLUT4 protein contents and hexokinase activity in skeletal muscle. PMID- 20362306 TI - The use of natural abundance stable isotopic ratios to indicate the presence of oxygen-containing chemical linkages between cellulose and lignin in plant cell walls. AB - Qualitative and quantitative understanding of the chemical linkages between the three major biochemical components (cellulose, hemicellulose and lignin) of plant cell walls is crucial to the understanding of cell wall structure. Although there is convincing evidence for chemical bonds between hemicellulose and lignin and the absence of chemical bonds between hemicellulose and cellulose, there is no conclusive evidence for the presence of covalent bonds between cellulose and lignin. This is caused by the lack of selectivity of current GC/MS-, NMR- and IR based methods for lignin characterisation as none of these techniques directly targets the possible ester and ether linkages between lignin and cellulose. We modified the widely-accepted "standard" three-step extraction method for isolating cellulose from plants by changing the order of the steps for hemicellulose and lignin removal (solubilisation with concentrated NaOH and oxidation with acetic acid-containing NaClO(2), respectively) so that cellulose and lignin could be isolated with the possible chemical bonds between them intact. These linkages were then cleaved with NaClO(2) reagent in aqueous media of contrasting (18)O/(16)O ratios. We produced cellulose with higher purity (a lower level of residual hemicellulose and no detectable lignin) than that produced by the "standard" method. Oxidative artefacts may potentially be introduced at the lignin removal stage; but testing showed this to be minimal. Cellulose samples isolated from processing plant-derived cellulose-lignin mixtures in media of contrasting (18)O/(16)O ratios were compared to provide the first quantitative evidence for the presence of oxygen-containing ester and ether bonds between cellulose and lignin in Zea mays leaves. However, no conclusive evidence for the presence or lack of similar bonds in Araucaria cunninghamii wood was obtained. PMID- 20362307 TI - Post-earthquake outbreak of insecticide-associated conjunctivitis in a primary school of Lixian district, China: An epidemiological investigation. AB - OBJECTIVES: To describe the time course and characteristics of an insecticide associated incident and highlight potential risks from similar outbreaks that may occur in other areas to enhance the preparedness of emergency physicians and other healthcare providers to deal with the sequelae of these events. STUDY DESIGN: Outbreak investigation METHODS: From 5 to 8 August 2008, an outbreak investigation was carried out among the affected primary school located in the refugee camp area of Lixian district, Sichuan, China. Affected pupils, parents, teachers and doctors working in the local medical stations were visited. Clinical checking, clinical treatment, epidemiological investigation and environmental investigation were undertaken. RESULTS: In total, 138 individuals were diagnosed with acute conjunctivitis, characterized by inflammation of the conjunctiva and intense ocular symptoms such as redness, itching and mucus discharge. According to the results, all risk factors (i.e. drinking water, indoor air and the materials used in camp classrooms) were excluded except insecticide exposure. The characteristics of symptoms, distribution of cases and records of irregular insecticide spraying support the assumption that the conjunctivitis outbreak was associated with synthetic pyrethroid alphacypermethrin exposure. CONCLUSION: The results suggest that non-standard operating procedures in pest control could lead to disease incidents. Medical rescue teams should receive training and education in preventive techniques. PMID- 20362309 TI - Comparison of nested PCR and real-time PCR for the detection of Toxoplasma gondii in biological samples from naturally infected cats. AB - There are different protocols of molecular diagnosis methods available including DNA extraction methods to diagnose of Toxoplasma gondii, being necessary to perform comparative studies in biological samples. The aim of this study is to compare real-time PCR (rtPCR) and nested PCR (nPCR) to evaluate the detection of T. gondii in naturally infected cats. Biological samples of Toxoplasma seropositive cats were assayed for detection of T. gondii DNA--extracted by both the lysis buffer and proteinase K (LB proteinase K) method and the acid guanidinium thiocyanate (GuSCN) method--using rtPCR and nPCR. T. gondii DNA was detected by nPCR in 43.6% and 40.8% of the samples from which it was extracted by the LB proteinase K and the GuSCN method, respectively. With rtPCR these figures fell significantly to 33.8% and 14.1%. Despite of nPCR showed higher sensitivity, the agreement observed between two PCRs was good; this agreement, however, was affected by the DNA extraction method used, LB proteinase K method showed better results. PMID- 20362310 TI - A novel NF-kappaB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors. AB - Lymphoid neoplasms including lymphoma and leukemia are one of the most life threatening disorders in dogs. Many lymphoid malignancies are well-treated with glucocorticoid (GC); however, GC resistance sometimes develops and its mechanism remains uncertain. Since constitutive activation of nuclear factor-kappaB (NF kappaB) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-kappaB activity with a synthetic inhibitor IMD-0354 affected GC sensitivity of canine neoplastic lymphoid cells, CL-1 and GL-1. Dexamethasone failed to inhibit proliferation of these cells, in which low expression of glucocorticoid receptors (GR) was identified. In the presence of IMD-0354, GR expressions in CL-1 and GL-1 were increased, consequently dexamethasone inhibited their proliferation. These results indicated that GR expression might be down-regulated by spontaneous activation of NF-kappaB, resulting in GC resistance. Taken together, interference of NF-kappaB activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies. PMID- 20362311 TI - Seroprevalence of antibodies to Encephalitozoon cuniculi and Encephalitozoon intestinalis in humans and animals. AB - The presence of antibodies against Encephalitozoon cuniculi (E. cuniculi) and Encephalitozoon intestinalis (E. intestinalis) was examined in 215 samples from humans and in 488 samples from five different species of domestic and companion animals in Slovakia. The 215 human samples and samples from 90 swine, 123 non infected cattle (cattle), 24 cattle infected with bovine leukosis virus (BLV positive cattle), 140 sheep and 111 dogs were examined by the enzyme-linked immunosorbent assay (ELISA). Samples with serum titres 1:200 or higher were considered as positive. Specific anti-E. cuniculi antibodies were found in humans (0.9%), swine (52%), cattle (2%), sheep (9%) and dogs (15%) except for the BLV positive cattle at the titre of 1:200. The titre of 1:400 was detected only in humans (0.5%). The presence of specific anti-E. intestinalis antibodies at the titre of 1:200 was confirmed in humans (6%), swine (51%), cattle (11%), BLV positive cattle (13%) and dogs (6%) but not in sheep. The anti-E. intestinalis antibodies reached the 1:400 in humans (1%), swine (4%) and BLV-positive cattle (17%). The presence of specific anti-E. intestinalis antibodies at the titre of 1:600 was observed only in one swine (1%). Significant differences were observed in animals at titres 1:200 and 1:400 (chi-squared test: p<0.0001) for both pathogens and in humans only for E. cuniculi at the titre of 1:400 (chi-squared test: p<0.0075). PMID- 20362312 TI - The effect on performance, energy metabolism and hepatic carotenoid content when phytase supplemented diets were fed to broiler chickens. AB - Two basal diets containing an adequate and a low supply of available P (4.7 vs 2.5 g/kg diet) and three others containing a low available P but supplemented with 250, 500 and 12,500 units of phytase (FTU) per kg diet, respectively, were prepared. Each diet was fed ad libitum to birds in six metabolism cages (five birds in each cage) in a randomised block design. It was found that birds fed a high (12,500 FTU) dosage of phytase grew faster (P<0.001) and retained proportionally more carotenoids in the liver (P<0.05) compared to birds fed unsupplemented diet. The results suggest that dietary phytase may improve the anti-oxidative status of birds fed low P diets through enhancing dietary carotenoid availability. PMID- 20362313 TI - Feline calicivirus VP2 is involved in the self-assembly of the capsid protein into virus-like particles. AB - Feline calicivirus (FCV) is considered the most common upper respiratory tract disease (URTD) associated pathogen in cats. We previously expressed FCV VP1 capsid protein in insect cells by baculovirus system and we observed that this protein self-assemble into virus-like particles (VLPs) different in size and lacking the typical cup-like depressions of caliciviruses. In the present study, VP1 and the small basic structural protein VP2 of FCV were individually expressed by baculovirus system. Coinfection of insect cells with both recombinant viruses resulted in VP1 and VP2 self-assembly to form depressions similar to native capsids in size and appearance, demonstrating that VP2 interacts with the VP1 protein in the formation of VLPs. PMID- 20362314 TI - Effect of Enterococcus faecium AL41 and Thymus vulgaris essential oil on small intestine integrity and antioxidative status of laying hens. AB - We investigated the effect of Enterococcus faecium on phagocytic activity, antioxidative status in vivo and the effect of E. faecium and 0.4% concentration of Thymus vulgaris essential oil (EO) on the duodenal tissue integrity in vitro in laying hens. The birds were fed the same standard diets and were divided into four groups. E. faecium was added to the drinking water for the second and fourth groups. EO was added to special chambers for measuring trans-epithelial electrical resistance (TEER) for the third and fourth groups only. TEER was lower in groups where EO was added, but in the group with E. faecium TEER was not changed significantly. Our results show that EO at 0.4% concentration may negatively affect intestine integrity, and the probiotic strain E. faecium AL41 is able to eliminate this effect and can strengthen non-specific immunity. To confirm our findings further histopathological investigations of intestinal tissue are needed. PMID- 20362315 TI - Feline immunodeficiency virus, feline leukemia virus and Toxoplasma gondii in stray and household cats in Kerman-Iran: seroprevalence and correlation with clinical and laboratory findings. AB - This study was carried out to determine the seroprevalence of feline leukemia virus (FeLV), feline immunodeficiency virus (FIV) and Toxoplasma gondii (T. gondii) infection among stray and owned cats in southeastern Iran and to identify the influence of age, sex, lifestyle, health status, and laboratory findings on seropositivity. The overall infection rate for FIV, FeLV, and T. gondii was 19.2%, 14.2%, and 32.1% respectively. Results of the multivariate logistic regression analysis showed that old adults more likely to be seropositive than juveniles for FIV, FeLV, and T. gondii (adjusted odds ratios [ORs], 1.84, 1.56, and 2.57 respectively). Anemic and diseased cats ([ORs], 6.62 and 0.9) were at a greater risk of testing positive for FeLV. Male cats were 4.91 times as likely to have FIV as were female and hyperglobulinemia was significantly more prevalent in FIV-infected cats ([ORs], 3.4). In conclusion, FIV and FeLV seem to be endemic in Iran and retroviral-associated immunosuppression may be a risk factor for active toxoplasmosis in infected cats. PMID- 20362316 TI - An integrated protein localization and interaction map for Potato yellow dwarf virus, type species of the genus Nucleorhabdovirus. AB - The genome of Potato yellow dwarf virus (PYDV; Nucleorhabdovirus type species) was determined to be 12,875 nucleotides (nt). The antigenome is organized into seven open reading frames (ORFs) ordered 3'-N-X-P-Y-M-G-L-5', which likely encode the nucleocapsid, phospho, movement, matrix, glyco and RNA-dependent RNA polymerase proteins, respectively, except for X, which is of unknown function. The ORFs are flanked by a 3' leader RNA of 149 nt and a 5' trailer RNA of 97 nt, and are separated by conserved intergenic junctions. Phylogenetic analyses indicated that PYDV is closely related to other leafhopper-transmitted rhabdoviruses. Functional protein assays were used to determine the subcellular localization of PYDV proteins. Surprisingly, the M protein was able to induce the intranuclear accumulation of the inner nuclear membrane in the absence of any other viral protein. Finally, bimolecular fluorescence complementation was used to generate the most comprehensive protein interaction map for a plant-adapted rhabdovirus to date. PMID- 20362317 TI - Investigating dissolved air flotation performance with cyanobacterial cells and filaments. AB - Dissolved air flotation (DAF) performance with two different naturally occurring cyanobacterial morphologies was investigated with respect to the biomass removal efficiency, the toxin release to water and the coagulant demand by different water background natural organic matter (NOM). Coagulation (C)/Flocculation (F)/DAF bench-scale experiments (2 min coagulation at 380 s(-1) with polyaluminium chloride (0.5-4 mg/L Al(2)O(3), the dose depending on the water NOM content); 8 min flocculation at 70 s(-1); 8 min DAF with 5 bar relative pressure and 8% pressurised recycle) were performed with single cells of Microcystis aeruginosa and Planktothrix rubescens filaments spiked in synthetic waters with different NOM contents (hydrophobic vs. hydrophilic NOM; moderate (2-3 mgC/L) vs. moderate-high concentration (ca. 6 mgC/L)). For both morphologies, the results show no apparent cyanobacterial damage (since the water quality did not degrade in dissolved microcystins and the removal of intracellular microcystins matched the removal of chlorophyll a) and high biomass removal efficiencies (93-99% for cells and 92-98% for filaments) provided optimal coagulant dose for chlorophyll a removal was ensured. Charge neutralisation by the polyaluminium chloride was the main coagulation mechanism of the M. aeruginosa cells and most likely also of the P. rubescens filaments. The specific coagulant demand was severely affected by NOM hydrophobicity, hydrophobic NOM (with a specific UV(254nm) absorbance, SUVA, above 4 L/(m mgC)) requiring ca. the triple of hydrophilic NOM (SUVA below 3 L/(m mgC)), i.e. 0.7 vs. 0.2-0.3 mg Al(2)O(3)/mg DOC. PMID- 20362318 TI - Robust predictive modelling of water pollution using biomarker data. AB - This paper describes the methodology of building a predictive model for the purpose of marine pollution monitoring, based on low quality biomarker data. A step-by-step, systematic data analysis approach is presented, resulting in design of a purely data-driven model, able to accurately discriminate between various coastal water pollution levels. The environmental scientists often try to apply various machine learning techniques to their data without much success, mostly because of the lack of experience with different methods and required 'under the hood' knowledge. Thus this paper is a result of a collaboration between the machine learning and environmental science communities, presenting a predictive model development workflow, as well as discussing and addressing potential pitfalls and difficulties. The novelty of the modelling approach presented lays in successful application of machine learning techniques to high dimensional, incomplete biomarker data, which to our knowledge has not been done before and is the result of close collaboration between machine learning and environmental science communities. PMID- 20362319 TI - Field solar degradation of pesticides and emerging water contaminants mediated by polymer films containing titanium and iron oxide with synergistic heterogeneous photocatalytic activity at neutral pH. AB - Photocatalytic degradation of phenol, nalidixic acid, mixture of pesticides, and another of emerging contaminants in water was mediated by TiO(2) and iron oxide immobilized on functionalized polyvinyl fluoride films (PVF(f)-TiO(2)-Fe oxide) in a compound parabolic collector (CPC) solar photoreactor. During degradation, little iron leaching (<0.2mgL(-1)) was observed. Phenol was efficiently degraded and mineralized at operational pH<5 and nalidixic acid degradation was complete even at pH 7, but mineralization stopped at 35%. Pesticide mixture was slowly degraded (50%) after 150min of irradiation. Degradation of the emergent contaminant mixture was successful for eight compounds and less efficient for six other compounds. The significant reactivity differences between tested compounds were assigned to the differences in structure namely that the presence of complexing or chelating groups enhanced the rates. PVF(f)-TiO(2)-Fe oxide photoactivity gradually increased during 20 days of experiments. X-ray photoelectron spectroscopy (XPS) measurements revealed significant changes on the catalyst surface. These analyses confirm that during photocatalysis mediated by PVF(f)-TiO(2)-Fe oxide, some iron leaching led to enlargement of the TiO(2) surface exposed to light, increasing its synergy with iron oxides and leading to enhanced pollutant degradation. PMID- 20362320 TI - The use of MSSV pyrolysis to assist the molecular characterisation of aquatic natural organic matter. AB - Microscale sealed vessel pyrolysis (MSSVpy) with online gas chromatography mass spectrometry (GC-MS) was used with several other established and complementary analytical methods to robustly characterize the structure of aquatic natural organic matter (NOM) and to practically assess the analytical value of MSSVpy. The NOM used in the study was from North Pine (NP) reservoir, which is one of the major source waters supplying Brisbane, the capital city of the Australian state of Queensland. The reservoir has moderate dissolved organic carbon (DOC; 5mgL( 1)) levels and is impacted by algae which periodically occur in bloom proportions. The hydrophobic (HPO; 65% initial DOC) and transphilic (TPI; 12%) fractions showed H/C values >1, low UV(abs) and low aryl-C measured by NMR which are all indicative of low aromaticity. MSSVpy produced distinctly higher product concentrations than traditional flash pyrolysis and the molecular profile of the HPO and TPI fractions revealed by MSSVpy was correlated with the other analytical data to help establish their structural relevance. Prolific distributions of alkyl substituted aromatic (e.g., benzenes, naphthalenes) and hydroaromatic (e.g., tetralins) products detected in the HPO fraction were attributed to the aromatisation of terpanes and other aliphatic compounds from algal, and possibly also plant sources. Alkyl phenols also detected in HPO in high abundance, are probably from algal biopolymers, but may also reflect a contribution from non methoxylated lignin units of catchment grasses. There was no analytical evidence of the dihydroxy or methoxy aromatic structures typical of wood lignin or tannin. N-organic pyrolysates (e.g., alkyl pyrroles, pyridines, indoles) of diagenetically altered proteins were concentrated in the TPI fraction. The quantitative importance of the N-organic moiety of the TPI fraction was corroborated by a low C/N ratio and distinctive amide and amine signals detected by (13)C NMR and FTIR. This integrated study demonstrates that the qualitative speciation provided by MSSVpy can make a significant contribution to the structural characterisation and source recognition of aquatic NOM. PMID- 20362321 TI - Effect of dissolved oxygen on the photodecomposition of monochloramine and dichloramine in aqueous solution by UV irradiation at 253.7 nm. AB - The effect of dissolved oxygen on the photodecomposition of monochloramine (7.5 < pH < 10) and dichloramine (pH = 3.7 +/- 0.2) at 253.7 nm has been investigated. The kinetic study shows that the rate of photodecomposition of monochloramine is about two times faster in the absence of oxygen than in the presence of oxygen, is not significantly affected by pH and by the presence of hydroxyl radical scavengers (hydrogenocarbonate ion and tert-butanol). The apparent quantum yields of photodecomposition of monochloramine at 253.7 nm ([NH(2)Cl](0) approximately 1.5-2 mM, epsilon(253.7 nm) = 371 M(-1) cm(-1)) were equal to 0.28 +/- 0.03 and 0.54 +/- 0.03 mol E(-1) in oxygenated-saturated and in oxygen-free solutions, respectively. The photodecomposition rates or the apparent quantum yields of photodecomposition of dichloramine ([NHCl(2)](0) approximately 1.5-2 mM, pH = 3.7 +/- 0.2) in oxygen-free and in oxygen-saturated solutions were quite identical (Phi = 0.82 +/- 0.08 mol E(-1); epsilon(253.7 nm) = 126 M(-1) cm(-1)). Under O(2) saturation, UV irradiation of NH(2)Cl leads to the formation of nitrite ( approximately 0.37 mol/mol of NH(2)Cl decomposed), nitrate ( approximately 0.073 mol/mol) and does not form ammonia (<0.01 mol/mol). In oxygen-free solutions, monochloramine decomposes to form ammonia ( approximately 0.37 mol/mol). Photodecomposition of dichloramine did not lead to significant amounts of nitrite and nitrate in the presence and in the absence of oxygen. The nitrogen mass balances also indicate the formation of other nitrogen species (probably N(2) and/or N(2)O) during the photodecomposition of monochloramine and dichloramine by UV irradiation at 253.7 nm. PMID- 20362322 TI - The microstructure of ferrihydrite and its catalytic reactivity. AB - Ferrihydrites were prepared by different mixing procedures of ferric and sodium hydroxide solutions. The microstructure of ferrihydrites was characterized by XRD, TG-DTA, BET surface and EXAFS. The catalytic activity of ferrihydrites toward degradation of Mordant Yellow 10 (MY10) and decomposition of hydrogen peroxide was evaluated. The results show that ferrihydrites, prepared by different procedures, display various physico-chemical properties, which can be well explained by the standard multiphase structural model of ferrihydrite. PMID- 20362323 TI - Maternal transfer of chlorinated contaminants in the leatherback turtles, Dermochelys coriacea, nesting in French Guiana. AB - We examined the maternal transfer of organochlorine contaminants (OCs), pesticides (DDTS and HCHs) and polychlorinated biphenyls (PCBs), and the temporal variation of blood and eggs concentrations from 38 leatherback turtles (Dermochelys coriacea) nesting in French Guiana. PCBs were found to be the dominant OCs with respective mean concentrations of 55.14 ng g(-1) lipid-mass for egg and 1.26 ng mL(-1) wet-mass for blood. OC concentrations were lower than concentrations measured in other marine turtles which might be due to the lower trophic position (diet based on gelatinous zooplankton) and to the location of their foraging and nesting grounds. All OCs detected in leatherback blood were detected in eggs, suggesting a maternal transfer of OCs. This transfer was shown to depend on female blood concentration for SigmaDDTs and for the most prevalent PCB congeners, since significant relationships were found between paired blood egg concentrations. During the nesting season, OC concentrations in eggs and the percentage of lipid in eggs were found to decline in successive clutches, highlighting a process of offloading from females to their eggs and a decreasing investment of lipid from females into their clutches. OCs in eggs tended to be higher in females spending 3 years in the foraging grounds between two nesting seasons than in those spending 2 years, suggesting an impact of time spacing two breeding seasons, called remigration interval, and of location of the foraging grounds. PMID- 20362324 TI - Early hominin dental remains from the Plio-Pleistocene site of Drimolen, South Africa. AB - The Plio-Pleistocene fossil hominin site of Drimolen is located approximately 5.5km north of the other well-known South African Plio-Pleistocene sites (Sterkfontein, Swartkrans, Kromdraai, Coopers). It was discovered by A.W. Keyser in 1992. Systematic excavations led to the recovery of a remarkable number of fossil vertebrate taxa, including hominins. Most of the specimens collected consist of isolated teeth or those in jaws. The aim of this paper is to provide a morphological description of the dental specimens. The taxonomic allocation of each specimen is also reported, either confirming or revising previous provisional attributions. The analysis confirms the occurrence of two hominin species, Paranthropus robustus and Homo sp. With over 80 fossil hominin specimens recovered so far, Drimolen is the second largest sample of P. robustus, after Swartkrans. At Drimolen, P. robustus is represented mostly by craniodental specimens (63) among which are 47 isolated teeth and the remainder are maxillary and mandibular fragments with teeth. The assemblage markedly increases the dental sample of P. robustus. Furthermore, the Drimolen sample includes tooth classes not present in the Swartkrans or Kromdraai samples. The new tooth classes include both deciduous upper lateral incisors (DNH 31) and canines (DNH 23). In the dental sample described here there are nine specimens probably attributable to Homo, although a specific attribution is not yet possible. These specimens expand the small sample of early Homo from South African sites. Basic dimensions (MD and BL) of the Drimolen dental remains are compared in a preliminary analysis with other hominin samples. This analysis delineates the Drimolen P. robustus dental sample as characterized by smaller teeth overall than the Swartkrans sample (and in some cases also smaller than the Kromdraai sample), as well as a greater size range. PMID- 20362326 TI - Effects of adhesive, base and diluent monomers on water sorption and conversion of experimental resins. AB - OBJECTIVES: To establish the relationship of resin composition and resin hydrophilicity (indicated by solubility parameters and logP) to water sorption (WS), solubility, and degree of double bond conversion (DC) of resin mixtures designed for adhesive restoratives by varying the concentration of pyromellitic glycerol dimethacrylate (PMGDM) and various co-monomers. METHODS: Sixteen resin mixtures were prepared with (30-70) mass fraction % PMGDM. At given PMGDM concentrations there were up to five compositions with increasing logP. Polymer disks (13 mm x 0.7 mm) were exposed to 96% relative humidity (RH) to determine water sorption in humid atmosphere (WSH) and subsequently immersed in water for immersion water sorption (WSI) and solubility. DC was assessed by near infrared spectroscopy. RESULTS: WSI was somewhat higher than WSH, which ranged from (2.1 to 5.3) mass fraction %. Both data were positively correlated to PMGDM concentrations [Pearson correlation, p<0.02; R(2)=0.74, 0.73 (WSI)] and solubility (R(2)=0.64), but not to logP. When grouped by structural similarities, i.e., base resins with bisphenol A core (Group B), Group O containing diluent monomers, or Group U containing urethane dimethacrylate, WS within each group was inversely correlated to logP with R(2)=0.98, 0.81, 0.95, and WS/solubility correlation improved with R(2)=0.88, 0.92 and 0.75, respectively. Solubility ranging from 0.3% to 2.3% was inversely related to DC (r=-0.872). Conversion ranging from 41% to 81% was lower for resins with high base monomer concentrations and highest in mixtures with UDMA. SIGNIFICANCE: LogP was a good predictor of WS after grouping the resins according to functional, compositional and structural similarities. WS and conversion were reasonably well predicted from Hoy's solubility parameters and other physical resin properties. PMID- 20362325 TI - 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. AB - Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4. Loss of 53BP1 alleviates hypersensitivity of Brca1 mutant cells to PARP inhibition and restores error-free repair by HR. Mechanistically, 53BP1 deletion promotes ATM-dependent processing of broken DNA ends to produce recombinogenic single-stranded DNA competent for HR. In contrast, Lig4 deficiency does not rescue the HR defect in Brca1 mutant cells but prevents the joining of chromatid breaks into chromosome rearrangements. Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations. PMID- 20362327 TI - The PROPATRIA trial: best practices at the time were followed. PMID- 20362328 TI - The influence of hierarchical hybrid micro/nano-textured titanium surface with titania nanotubes on osteoblast functions. AB - Hierarchical hybrid micro/nano-textured titanium surface topographies with titania nanotubes were produced by simple acid etching followed by anodization to mimic the hierarchical structure of bone tissues. Primary rat osteoblasts were used to evaluate the bioactivity. The microtopography formed by acid etching of titanium induced inconsistent osteoblast functions with initial cell adhesion and osteogenesis-related gene expression being dramatically enhanced while other cell behaviors such as proliferation, intracellular total protein synthesis and alkaline phosphatase activity, collagen secretion, and extracellular matrix mineralization being depressed. In comparison, addition of nanotubes to the microtopography led to enhancement of multiple osteoblast functions. Nearly all the cell functions investigated in this study were retained or promoted. Compared to a microtopography, the enhancement of multiple cell functions observed from the hierarchical micro/nano-textured surfaces is expected to lead to faster bone maturation around the titanium implants without compromising the bone mass. In addition, the hierarchical micro/nano-textured surfaces still retain the mechanical interlocking ability of the microtopography thereby boding well for osseointegration. Our study reveals a synergistic role played by the micro and nanotopographies in osteoblast functions and provides insight to the design of better biomedical implant surfaces. PMID- 20362329 TI - Cell contraction forces in scaffolds with varying pore size and cell density. AB - The contractile behavior of cells is relevant in understanding wound healing and scar formation. In tissue engineering, inhibition of the cell contractile response is critical for the regeneration of physiologically normal tissue rather than scar tissue. Previous studies have measured the contractile response of cells in a variety of conditions (e.g. on two-dimensional solid substrates, on free-floating tissue engineering scaffolds and on scaffolds under some constraint in a cell force monitor). Tissue engineering scaffolds behave mechanically like open-cell elastomeric foams: between strains of about 10 and 90%, cells progressively buckle struts in the scaffold. The contractile force required for an individual cell to buckle a strut within a scaffold has been estimated based on the strut dimensions (radius, r, and length, l) and the strut modulus, E(s). Since the buckling force varies, according to Euler's law, with r(4)/l(2), and the relative density of the scaffold varies as (r/l)(2), the cell contractile force associated with strut buckling is expected to vary with the square of the pore size for scaffolds of constant relative density. As the cell density increases, the force per cell to achieve a given strain in the scaffold is expected to decrease. Here we model the contractile response of fibroblasts by analyzing the response of a single tetrakaidecahedron to forces applied to individual struts (simulating cell contractile forces) using finite element analysis. We model tetrakaidecahedra of different strut lengths, corresponding to different scaffold pore sizes, and of varying numbers of loaded struts, corresponding to varying cell densities. We compare our numerical model with the results of free-floating contraction experiments of normal human dermal fibroblasts (NHDF) in collagen-GAG scaffolds of varying pore size and with varying cell densities. PMID- 20362330 TI - Bactericidal behaviour of Ti6Al4V surfaces after exposure to UV-C light. AB - TiO(2)-coated biomaterials that have been excited with UV irradiation have demonstrated biocidal properties in environmental applications, including drinking water decontamination. However, this procedure has not been successfully applied towards the killing of pathogens on medical titanium-based implants, mainly because of practical concerns related to irradiating the inserted biomaterial in situ. Previous researchers assumed that the photocatalysis on the TiO(2) surface during UV application causes the bactericidal effects. However, we show that a residual post-irradiation bactericidal effect exists on the surface of Ti6Al4V, not related with photocatalysis. Using a combination of staining, serial dilutions, and a biofilm assay, we show a significant and time-dependent loss in viability of different bacterial strains of Staphylococcus epidermidis and Staphylococcus aureus on the post-irradiated surface. Although the duration of this antimicrobial effect depends on the strains selected, our experiments suggest that the effect lasts at least 60 min after surface irradiation. The origin of such phenomena is discussed in terms of the physical properties of the irradiated surfaces, which include the emission of energy and changes in surfaces charge occurring during electron-hole recombination processes. The method here proposed for the preparation of antimicrobial titanium surfaces could become especially useful in total implant surgery for which the antimicrobial challenge is mainly during or shortly after surgery. PMID- 20362331 TI - Expression of syncytin in leukemia and lymphoma cells. AB - Syncytin is a placenta-specific protein and generally believed to play a pivotal role in syncytiotrophoblast morphogenesis. In this study, transcripts of this gene were quantified by real-time RT-PCR and the translated products were measured by an indirect immunofluorescence assay. Results showed that syncytin was found to be expressed in all nine leukemia and lymphoma cell lines studied albeit at different levels and in 43 peripheral blood samples of 57 leukemia or lymphoma patients. Neither the transcripts nor the translated syncytin was detected in blood samples of normal individuals. In conclusion, peripheral blood syncytin may serve as a marker for leukemia and lymphoma. PMID- 20362332 TI - Guillain-Barre syndrome after use of alemtuzumab (Campath) in a patient with T cell prolymphocytic leukemia: a case report and review of the literature. PMID- 20362333 TI - Circulating Ki-67 index in plasma as a biomarker and prognostic indicator in chronic lymphocytic leukemia. AB - Ki-67 is a nuclear antigen that is expressed in all stages of the cell cycle, except G(0), and is widely used as a marker of cellular proliferation in human tumors. We recently showed that elevated levels of Ki-67 circulating in plasma (cKi-67) are associated with shorter survival in patients with acute lymphoblastic leukemia. The current study included 194 patients with CLL and 96 healthy control subjects. cKi-67 levels in plasma were determined using an electrochemiluminescent immunoassay. We normalized the cKi-67 level to the absolute number of lymphocytes in the patient's peripheral blood to establish the plasma cKi-67 index. The cKi-67 index showed significant correlation with lymph node involvement and Rai stage (P=0.05). Higher cKi-67 index values were significantly associated with shorter survival. Multivariate Cox proportional hazards regression analysis demonstrated that the association of the cKi-67 index with shorter survival was independent of IgV(H) mutation status. In a multivariate model incorporating the cKi-67 index with B2M and IgV(H), only cKi 67 index and B2M levels remained as independent predictors of survival. The results of this study suggest that the plasma cKi-67 index, along with B2M level, is a strong predictor of clinical behavior in CLL. PMID- 20362334 TI - CD5+ B-cell lymphoproliferative disorders: Beyond chronic lymphocytic leukemia and mantle cell lymphoma. AB - CD5 positivity in B-cell lymphoproliferative disorders (LPD) is usually considered characteristic of either chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). However, other neoplastic B-LPDs may express CD5, albeit infrequently. In this study we have reviewed the tissue pathology of CD5+ B-LPDs that do not fulfill diagnostic criteria for CLL or MCL on flow cytometric studies of peripheral blood or bone marrow. Our results indicate that although CD5 positivity is most commonly associated with CLL and MCL, a significant minority of cases do not fall into these two categories. Phenotypically unusual CLL, marginal zone lymphoma and lymphoplasmacytic lymphoma were the most common diagnoses in this group of patients. Applying strict flow cytometry criteria, using genetic studies, and deferring to a lymph node/tissue diagnosis in non classical cases are critical for accurate diagnosis and classification of CD5+ B cell LPD. PMID- 20362335 TI - Does monosomy 5 really exist in myelodysplastic syndromes and acute myeloid leukemia? AB - Abnormalities of chromosome 5 are common aberrations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), being del(5q) the most frequent. In contrast, monosomy 5 is not so frequent and, usually, is associated with complex karyotypes, conferring poor prognosis. The aim of this study was to analyze, by FISH for 5q31 (EGR1), a series of 28 MDS and AML cases with monosomy 5 detected by G-banding. FISH results revealed deletion of 5q31 in 24 of them (85.7%) and monosomy 5 just in three. FISH for 5q31 can complement conventional cytogenetics and improve the karyotype definition, leading to a better diagnostic and prognostic stratification. PMID- 20362336 TI - Characterization of a cashew allergen, 11S globulin (Ana o 2), conformational epitope. AB - Both linear and conformational epitopes likely contribute to the allergenicity of tree nut allergens, yet, due largely to technical issues, few conformational epitopes have been characterized. Using the well studied recombinant cashew allergen, Ana o 2, an 11S globulin or legumin, we identified a murine monoclonal antibody which recognizes a conformational epitope and competes with patient IgE Ana o 2-reactive antibodies. This epitope is expressed on the large subunit of Ana o 2, but only when associated with an 11S globulin small subunit. Both Ana o 2 and the homologous soybean Gly m 6 small subunits can foster epitope expression, even when the natural N-terminal to C-terminal subunit order is reversed in chimeric molecules. The epitope, which is also expressed on native Ana o 2, is readily susceptible to destruction by physical and chemical denaturants. PMID- 20362337 TI - TLR4-independent upregulation of activation markers in mouse B lymphocytes infected by HRSV. AB - Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. In addition, HRSV poses a serious health risk in immunocompromised individuals and the elderly. It has been reported that this virus can infect mouse antigen-presenting cells, including B lymphocytes. In these B cells, HRSV infection upregulates the expression of activation markers, including MHC class II and CD86, but not MHC class I molecules. Here, we report that HRSV infection of spleen B lymphocytes downregulated TLR4. Either blocking with anti-TLR4 antibody or genetic deletion, but not functional deficiency of TLR4, moderately reduced the infectivity of HRSV in B lymphocytes. HRSV-infected B lymphocytes with deleted TLR4 upregulated MHC class II and CD86 molecules to the same levels as TLR4(+) wild type B cells. Since the activation of monocytes and macrophages by HRSV was previously reported to depend on TLR4, the current study indicates that these cells and B lymphocytes respond to HRSV infection with different activation pathways. PMID- 20362338 TI - Mapping of a conformational epitope on the cashew allergen Ana o 2: a discontinuous large subunit epitope dependent upon homologous or heterologous small subunit association. AB - The 11S globulins are members of the cupin protein superfamily and represent an important class of tree nut allergens for which a number of linear epitopes have been mapped. However, specific conformational epitopes for these allergens have yet to be described. We have recently reported a cashew Ana o 2 conformational epitope defined by murine mAb 2B5 and competitively inhibited by a subset of patient IgE antibodies. The 2B5 epitope appears to reside on the large (acidic) subunit, is dependent upon small (basic) subunit association for expression, and is highly susceptible to denaturation. Here we fine map the epitope using a combination of recombinant chimeric cashew Ana o 2-soybean Gly m 6 chimeras, deletion and point mutations, molecular modeling, and electron microscopy of 2B5 Ana o 2 immune complexes. Key residues appear confined to a 24 amino acid segment near the N-terminus of the large subunit peptide, a portion of which makes direct contact with the small subunit. These data provide an explanation for both the small subunit dependence and the structurally labile nature of the epitope. PMID- 20362339 TI - Control of reduction thermodynamics in [2Fe-2S] ferredoxins Entropy-enthalpy compensation and the influence of surface mutations. AB - The reaction thermodynamics for the one-electron reduction of the [2Fe-2S] cluster of both human ferredoxin and various surface point mutants, in which each of the negatively charged residues Asp72, Glu73, Asp76, and Asp79 were converted to Ala, have been determined by variable temperature spectroelectrochemical measurements. The above are conserved residues that have been implicated in interactions between the vertebrate-type ferredoxins and their redox partners. In all cases, and similar to other 2Fe-ferredoxins, the reduction potentials are negative as a result of both an enthalpic and entropic stabilization of the oxidized state. Although all Hs Fd mutants, with the exception of Asp72Ala, show slightly higher E degrees ' values than that of wild type Hs Fd, according to expectations for a purely electrostatic model, they exhibit changes in the H degrees '(rc) values that are electrostatically counter-intuitive. The observation of enthalpy-entropy compensation within the protein series indicates that the mutation-induced changes in H degrees '(rc) and S degrees '(rc) are dominated by reduction-induced solvent reorganization effects. Protein-based entropic effects are likely to be responsible for the low E degrees ' value of D72A. PMID- 20362340 TI - The synthesis and toxicity of tripodal tricarbonyl rhenium complexes as radiopharmaceutical models. AB - We report the synthesis and toxicity of a series of rhenium(I) tricarbonyl complexes incorporating the trisaminomethylethane (TAME) ligand. Compounds with the (TAME)Re(CO)(3)(+) cation were synthesized via several routes, including by use of Re(CO)(5)X precursors as well as the aqueous cation Re(CO)(3)(H(2)O)(3)(+). Salts of the formula [(TAME)Re(CO)(3)]X where X=Br(-), Cl(-), NO(3)(-), PF(6)(-) and ClO(4)(-) were evaluated using two cell lines: the monoclonal S3 HeLa line and a vascular smooth muscle cell line harvested from mice. All compounds have isostructural cations and differ only in the identity of the non-coordinating anion. None of the complexes exhibited any appreciable toxicity in the HeLa line up to the solubility limit. In the vascular smooth muscle cell line, the bromide salt exhibited some cytotoxicity, but this observation most likely results from the presence of bromide anion, which has been shown to have limited toxicity. PMID- 20362341 TI - Contagious crying beyond the first days of life. AB - Newborns cry in response to another newborn cry and researchers agree that these are the very early signs of empathy development. Yet, little is known about the development of these affect sharing reactions in infancy, beyond the very first few days after birth. The aim of this study is to investigate the presence of contagious cry phenomenon in infancy. Infants aged 1-, 3-, 6-, and 9-month-old were presented with the sound of another infant cry vocalizations. Their emotional reactions were recorded in terms of vocal (presence of vocal distress, latency, and intensity) and facial (anger and sadness) expressions of emotions. Results show that during the presentation of a pain cry sound, 1, 3, 6, and 9 months old infants manifest increased vocal and facial expressions of distress. These affect sharing reactions do not decrease with age. Both boys and girls manifest similar levels of contagious crying reactions. The results are discussed in terms of early empathy development. PMID- 20362342 TI - Comparison of distress and pain in infants randomized to groups receiving standard versus multiple immunizations. AB - This randomized controlled trial compared distress and pain in healthy 4-month old infants receiving three different immunizations either sequentially (control, n=50) or simultaneously, two at the same time, followed by the third (experimental, n=51). Although both groups demonstrated a significant increase in cortisol from baseline levels, the lack of significant difference on salivary cortisol between groups post-immunization suggests the study was underpowered. On NIPS scores, the experimental group demonstrated significantly less pain (Mann Whitney U=1648.0, p=0.003). Simultaneous injections appeared to be effective in reducing pain behavior responses in infants receiving their 4-month immunizations. Longitudinal studies could determine whether reduced exposure to pain in infancy, through simultaneous immunization injections, could contribute to a reduction in sensitivity to pain and physiologic stress responses. PMID- 20362343 TI - Attitudes of patients with schizophrenia and depression towards psychiatric research. AB - The success of clinical research depends heavily on patients' willingness to participate in studies. In recent years much work has been dedicated to studying the problems of conducting research in psychiatry, mainly in schizophrenia patients. In an attempt to replicate previous findings and extend results beyond schizophrenia, we interviewed patients suffering from schizophrenia or depression in a large academic centre concerning their attitudes towards psychiatric research. Ninety-five patients with a diagnosis of schizophrenia (48) or depression (47) completed the "Hamburg General Attitudes to Psychiatric Research Questionnaire" self-report instrument. Furthermore, demographic and clinical data were collected. Illness severity was evaluated using Clinical Global Impression and Global Assessment of Functioning scores. In general, patients approved of psychiatric research, and attitudes towards specific areas of research and research methods were rather positive. There were no significant differences between the two diagnostic groups regarding reasons for participation or non participation in a clinical trial. The theoretical willingness to participate in studies was highest for studies using a questionnaire. Receiving sufficient information about a study before taking part was stated to be highly important. Our findings confirm and extend those of other groups. This should encourage psychiatrists at least in academic settings where most of this research has been done to approach patients to take part in clinical research. PMID- 20362344 TI - Effects of exposure to Prestige-like heavy fuel oil and to perfluorooctane sulfonate on conventional biomarkers and target gene transcription in the thicklip grey mullet Chelon labrosus. AB - Thicklip grey mullets Chelon labrosus inhabit coastal and estuarine areas where they can be chronically exposed to commonly released pollutants such as polycyclic aromatic hydrocarbons (PAHs) and perfluorinated compounds. These pollutants can also originate from accidental spills, such as the Prestige oil spill in 2002, which resulted in the release of a heavy fuel oil that affected coastal ecosystems in the Bay of Biscay. Peroxisome proliferation (PP), induced biotransformation metabolism, immunosuppression and endocrine disruption are some of the possible biological effects caused by such chemicals. With the aim of studying the effects of organic toxic chemicals on such biological processes at the transcriptional and at the cell/tissue level, juvenile mullets were exposed to the typical mammalian peroxisome proliferator perfluorooctane sulfonate (PFOS), and to fresh (F) and weathered (WF) Prestige-like heavy fuel oil for 2 and 16 days. First, fragments of genes relevant to biotransformation, immune/inflammatory and endocrine disruption processes were cloned using degenerate primers. Fuel oil elicited a significant PP response as proved by the transcriptional upregulation of palmitoyl-CoA oxidase (aox1), peroxisome proliferator activated receptor alpha (pparalpha) and retinoic X receptor, by the AOX1 activity induction and by the increased peroxisomal volume density. PFOS only elicited a significant induction of AOX1 activity at day 2 and of PPARalpha mRNA expression at day 16. All treatments significantly increased catalase mRNA expression at day 16 in liver and at day 2 in gill. Cyp1a transcription (liver and gill) and EROD activity were induced in fuel oil treated organisms. In the case of phase II metabolism only hepatic glutathione S-transferase mRNA was overexpressed in mullets exposed to WF for 16 days. Functionally, this response was reflected in a significant accumulation of bile PAH metabolites. WF treated fish accumulated mainly high molecular weight metabolites while F exposure resulted in accumulation of mainly low molecular ones. Fuel oil significantly regulated immune response related complement component C3 and hepcidin transcription followed by a significant regulation of inflammatory response related apolipoprotein-A1 and fatty acid binding protein mRNAs at day 16. These responses were accompanied by a significant hepatic inflammatory response with lymphocyte accumulations (IRLA) and accumulation of melanomacrophage centers (MMC). PFOS did not elicit any transcriptional response in the studied biotransformation and immune related genes, although histologically significant effects were recorded in IRLA and MMC. A significant reduction of lysosomal membrane stability was observed in all exposed animals. No endocrine disruption effects were observed in liver while brain aromatase mRNA was overexpressed after all treatments at day 2 and estrogen receptor alpha was downregulated under WF exposure at day 16. These results show new molecular and cellular biomarkers of exposure to organic chemicals and demonstrate that in mullets PP could be regulated through molecular mechanisms similar to those in rodents, although the typical mammalian peroxisome proliferator PFOS and heavy fuel oil follow divergent mechanisms of action. PMID- 20362345 TI - Behavioural changes in three species of freshwater macroinvertebrates exposed to the pyrethroid lambda-cyhalothrin: laboratory and stream microcosm studies. AB - Pesticides are transported from crop fields to adjacent streams via surface run off, drains, groundwater, wind drift and atmospheric deposition and give rise to transient pulse contamination. Although the concentrations observed, typically <10 microg L(-1), cannot be expected to be acutely lethal, effects in streams at the population and ecosystem level have been reported. One of the most conspicuous phenomena associated with these transient pesticide pulses is drift, where large numbers of freshwater invertebrates are carried along by the current and disappear from the contaminated stretch of the stream. The aim of the present study was to evaluate the feasibility of linking laboratory studies of the sublethal effects of pulse exposure to the pyrethroid lambda-cyhalothrin on the locomotory behaviour of stream invertebrates with effects on drift behaviour under more environmentally realistic conditions in stream microcosms. In the laboratory as well as in the microcosms, the order of sensitivities of the three species tested was (with Leuctra nigra being the most sensitive): L. nigra>Gammarus pulex>Heptagenia sulphurea. The LOECs determined for L. nigra (1 ng L(-1)), G. pulex (10 ng L(-1)) and H. sulphurea (100 ng L(-1)) are all within expected environmental concentrations. For the species of invertebrates investigated, it was possible to extrapolate directly from pyrethroid-induced behavioural changes observed in the laboratory to drift under more realistic conditions in stream microcosms. Consequently, the fast and cost-effective video tracking methodology may be applied for screening for potential effects of a wider range of pesticides and other stressors on the locomotory behaviour of freshwater invertebrates. The results indicate that such behavioural changes may be predictive of effects at the ecosystem level. PMID- 20362346 TI - A testimony to the history of heart and lung transplantation: English translation of Demikhov's paper, "Transplantation of the Heart, Lungs and other Organs". AB - Vladimir Petrovich Demikhov, a Soviet physiologist and surgeon, made meticulous attempts at reviving heart and lung transplantation in the last century. Herein, we present an English translation of Demikhov's 1969 paper of Transplantation of the Heart, Lungs and other Organs (published in Eksperimental'naia Khirurgiia i Anesteziologiia), which represented a synopsis of his experiences with experimental transplantation. A brief account of Demikhov's life and contributions to transplant medicine is also given. PMID- 20362347 TI - Should all patients with non-valvular atrial fibrillation be anticoagulated? AB - Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The prevalence and incidence of AF are rising, as confirmed in several European and American registries. Guidelines published in 2008 from the European Society of Cardiology/American Heart Association and from the American College of Chest Physicians, clarified the strategy of antithrombotic treatment in AF, which is based on the presence of risk factors for thromboembolism. This approach allows physicians to classify patients as at low, moderate or high risk, according to their individual risk characteristics, which are relatively similar in both sets of recommendations. Patients at moderate risk, however, who might justify anticoagulant or antiplatelet treatment, could be better characterized using morphological (echocardiographic) and/or biological factors or risk markers. Recent data have shown that the existence of a thrombogenic milieu in the left atrium (e.g., dilatation of the left atrial appendage and/or thrombus and/or spontaneous echocontrast and/or reduced emptying/filling flow velocity) indicates a higher risk of embolism and mortality. Furthermore, high-sensitivity C-reactive protein and haemostasis markers of coagulation are associated with thromboembolic risk and excess mortality in AF. Although current recommendations for the management of AF are not based on such markers, both could help physicians choose the optimal antithrombotic treatment (either vitamin K antagonists or antiplatelet drugs) according to the patient's specific risk profile. Nowadays, registries confirm under-prescription of vitamin K antagonist treatment in the 'real world,' even in patients at high thromboembolic risk, and over-prescription for at least one-third of low-risk patients. It is crucially important to realize that the risk of bleeding in patients with risk factors (e.g., older age, hypertension) is close to the risk of thromboembolism, which can have devastating outcomes in patients in AF. Alternative and efficient strategies (new oral anticoagulants, non-surgical closure of the left atrial appendage using percutaneous devices) are currently under investigation. Therefore reducing the risk of thromboembolism should be physicians' primary aim, particularly with the advent of alternative treatments and the development of new antithrombotic drugs such as oral thrombin and factor Xa inhibitors, which are currently being evaluated in clinical trials. PMID- 20362348 TI - Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years. AB - BACKGROUND AND PURPOSE: The effect of predominating Gleason grade (3+4 versus 4+3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA < or = 10 ng/ml, localised PCa is reported. MATERIALS AND METHODS: Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA < or = 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS). RESULTS: Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3+4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4+3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D(90) > or = 140 Gy (50% total), compared with 77.0% below 140 Gy (p=0.08). CONCLUSIONS: Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy. PMID- 20362349 TI - Point-of-care outcome assessment in the cancer clinic: audit of data quality. AB - BACKGROUND AND PURPOSE: To assess the completeness and accuracy of stage and outcome data in the Anthology of Outcomes (AOs), a prospective point-of-care physician-collected electronic data system for patients at the Princess Margaret Hospital. MATERIAL AND METHODS: A random sample of 10% of the AO cases registered between July 2003 and December 2005 was drawn. An audit was conducted of the AO data compared with chart review and cancer registry. RESULTS: The AO system was applied first to a head and neck (HN) cancer patient cohort. From 1152 HN cases, 120 were audited. TNM stage was recorded in all cases. Discrepancy was found between the AO and primary data sources in 3-13% of cases. Physician review showed a 3% error rate in overall stage recorded in the AO. Sixty-two outcomes in 43 patients were found on chart review. No outcomes were incorrectly recorded in the AO. Nineteen (31%) outcomes in 17 patients were missed in the AO. CONCLUSIONS: Our experience has demonstrated the feasibility of real-time outcome recording at point-of-care. New processes needed to improve the completeness of capture of patient outcomes in the AO have more recently been introduced. This successful system has been expanded to other disease sites. PMID- 20362350 TI - Clinical outcome after repeated radiosurgery for brain arteriovenous malformations. AB - INTRODUCTION: We assessed the clinical and radiological outcome after repeated radiosurgery for brain arteriovenous malformations (bAVMs) after failure of initial radiosurgery. MATERIALS AND METHODS: Fifteen patients underwent repeated radiosurgery. The mean bAVM volume at first radiosurgery (S1) was 4.6 +/- 4.3 ml and that at second radiosurgery (S2) was 2.1 +/- 2.5 ml. The median marginal dose was 18 Gy at S1, and 21 Gy at S2. Modified Rankin Scale (MRS) score was determined in all patients at last follow-up (FU). RESULTS: Complete obliteration was reached in nine patients (60%). Median time to obliteration was 50 months after S2. An excellent outcome (no new neurologic deficiencies, complete obliteration) was reached in seven patients (47%). Eleven patients (73%) showed a MRS1. Radiation-induced complications occurred in 20%, of which 13% occurred after S2. Radiological complications included cyst formation (n = 1), radiation related edema (n = 4), and radiation necrosis (n = 1), resulting in an increasing mean MRS of 0.5 at S1, 0.6 at S2, to 0.8 at FU. No (re-)bleedings were encountered during 137-patient years at risk. DISCUSSION: Repeated radiosurgery is a viable option for the treatment of small remnant bAVMs. We report 20% permanent radiation-induced complications. Such complications were mainly seen in relatively large, and therefore difficult to treat, bAVMs. PMID- 20362351 TI - In vitro modulation of the human gastrointestinal microbial community by plant derived polysaccharide-rich dietary supplements. AB - The use of prebiotics is a possible strategy to manage and steer the complex gut microbial community towards a health-promoting composition (Gastrointestinal Resource Management). In this study, the Simulator of the Human Intestinal Microbial Ecosystem was used to investigate the effects of two commercially available plant polysaccharide supplements on the structure, composition and metabolism of an in vitro cultured colon microbial community. Microbial analyses showed both a bifidogenic (up to +1.3 log cfu/mL) and a lactobacillogenic (up to +0.9 log cfu/mL) effect during treatment with the dietary supplements. Quantitative PCR confirmed that the increase of Bifidobacteria spp. was statistically significant (P<0.05) in all of the colon compartments and showed a significant increase of the bacteroides-prevotella group concentration (+0.6 log cells/ml) in the compartment simulating the proximal colon. Denaturant gradient gel electrophoresis analyses and a relative ecological interpretation, in combination with sugar and short-chain fatty acids quantification, provided evidence of a positive effect of both the tested products. Overall, the treatment period was associated with (i) good and selective fermentability of the polysaccharide supplements along the entire colon; (ii) positive and selective bifidogenic effect; (iii) the possibility of enhancing species belonging to Bacteroidetes, a phylum recently associated with body weight management. PMID- 20362352 TI - Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall. AB - The human airway epithelium serves as structural and functional barrier against inhaled particulate antigen. Previously, we demonstrated in an in vitro epithelial barrier model that monocyte derived dendritic cells (MDDC) and monocyte derived macrophages (MDM) take up particulate antigen by building a trans-epithelial interacting network. Although the epithelial tight junction (TJ) belt was penetrated by processes of MDDC and MDM, the integrity of the epithelium was not affected. These results brought up two main questions: (1) Do MDM and MDDC exchange particles? (2) Are those cells expressing TJ proteins, which are believed to interact with the TJ belt of the epithelium to preserve the epithelial integrity? The expression of TJ and adherens junction (AJ) mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence, respectively. Particle uptake and exchange was quantified by flow cytometry and laser scanning microscopy in co-cultures of MDM and MDDC exposed to polystyrene particles (1 MUm in diameter). MDM and MDDC constantly expressed TJ and AJ mRNA and proteins. Flow cytometry analysis of MDM and MDDC co cultures showed increased particle uptake in MDDC while MDM lost particles over time. Quantitative analysis revealed significantly higher particle uptake by MDDC in co-cultures of epithelial cells with MDM and MDDC present, compared to co cultures containing only epithelial cells and MDDC. We conclude from these findings that MDM and MDDC express TJ and AJ proteins which could help to preserve the epithelial integrity during particle uptake and exchange across the lung epithelium. PMID- 20362353 TI - The arylstibonic acid compound NSC13746 disrupts B-ZIP binding to DNA in living cells. AB - The inhibition of DNA binding of basic leucine zipper (B-ZIP) transcription factors is a clinically relevant molecular target. Our laboratory has previously reported two methods of inhibiting B-ZIP DNA binding in solution: 1) an arylstibonic acid compound that binds to the basic region, stabilizes the B-ZIP dimer, and prevents B-ZIP DNA binding and 2) dominant negative proteins, termed A ZIPs, that heterodimerize with B-ZIP domains in a leucine zipper-dependent manner. To determine if these two agents also inhibit DNA binding in live cells, GFP-tagged B-ZIP domains and mCherry-tagged A-ZIP domains were transfected into NIH3T3 cells to assess protein localization and Fluorescence Recovery After nuclear Photobleaching (FRAP). FRAP, showed that all six GFP-B-ZIP domains examined recovered faster in the nucleus in the presence of drug that we interpret represents an inhibition of DNA binding. Faster recovery in the presence of the A-ZIP was leucine zipper dependent. The arylstibonic also induced a cytoplasmic localization of all B-ZIP domains while the A-ZIPs induced a leucine zipper-dependent cytoplasmic localization. Thus, the change in cellular localization of B-ZIP domains could be used as a high-throughput assay for inhibitors of B-ZIP DNA binding. Additionally, the arylstibonic acid compound was cytostatic in clear cell sarcoma cells, which express a chimera between the B-ZIP domain of ATF-1 and N-terminal activation domain of EWS but not in K562 cells that express a non-B-ZIP containing chimeric protein BCR-ABL. These studies suggest that arylstibonic acid compounds or other small molecules capable of inhibiting B-ZIP DNA binding could be valuable anticancer agents. PMID- 20362354 TI - Prevalence of hospital-acquired infections and antibiotic use in two tertiary Mongolian hospitals. AB - Health statistics of Mongolia indicate that hospital-acquired infections (HAIs) occur in 0.01-0.05% of all hospital admissions. This is considerably lower than internationally reported rates. A one-day survey was conducted in two tertiary hospitals of Ulaanbaatar in September 2008 to estimate HAI prevalence, associated risk factors and patterns of antibiotic usage. Among 933 patients surveyed, 50 (5.4%) were diagnosed with HAI. Prevalence of surgical site infection was 1.1% (3.9% among surgical patients), bloodstream infection 0.3%, respiratory tract infection 1.3%, urinary tract infection 1.3%, and other HAI 1.4%. Microbiological investigations were only documented for 18.9% of all patients. A total of 558 patients (59.8%) were taking 902 courses of antibiotics; 92.1% of patients were prescribed antibiotics without a sensitivity test. Multiple logistic regression analysis revealed that HAI was significantly associated with the admission source, the hospital, length of hospital stay, surgical and other invasive procedures, urinary catheters and other indwelling devices. The study results were comparable with reports from some other developing countries and confirm that official statistics underestimate the true frequency of HAI in Mongolia. PMID- 20362355 TI - [Introduction series "Up-date". The critical patient with severe infection]. PMID- 20362356 TI - [Frequency of adverse reactions after influenza vaccination in health care personnel of a university hospital in Spain]. AB - INTRODUCTION: One of the reported arguments to health-care personnel receiving influenza vaccination is fear of Adverse Reactions (AR). The objective of this study was to investigate the frequency and characteristics of AR associated with the influenza vaccine. METHODS: Cohort study; 2587 health-care workers vaccinated against influenza during the seasons 2006-2007, 2007-2008 and 2008-2009 were included. They were asked about any AR seven days after the vaccination. RESULTS: A total of 1893 health-care workers were evaluated (73.2%). An AR was reported by 30.3%. There were no serious AR reported. CONCLUSION: The fear of the severity of AR does not seem to be justifiable as a reason for refusing the flu vaccine. PMID- 20362357 TI - Synthesis, structures, and urease inhibitory activities of three copper(II) and zinc(II) complexes with 2-{[2-(2-hydroxyethylamino)ethylimino]methyl}-4 nitrophenol. AB - In order to explore novel urease inhibitors, three new mononuclear complexes of Cu(II) and Zn(II) with Schiff base 2-{[2-(2-hydroxyethylamino)ethylimino]methyl} 4-nitrophenol have been prepared and structurally characterized by X-ray crystallography. Among the three complexes, two Cu(II) complexes show strong urease inhibitory activities with the IC(50) values being much lower than that of the acetohydroxamic acid, while the Zn(II) complex shows no activity at the concentration of 100 microM. PMID- 20362358 TI - Some new biologically active metal-based sulfonamide. AB - A new series of sulfonamide derived Schiff bases has been synthesized by a condensation reaction of various sulfonamides with aromatic aldehydes. The so obtained sulfonamide were further investigated for their chelation and biological properties with first row d-transition metal ions [cobalt(II), copper(II), nickel(II) and zinc(II)]. The nature of bonding and structure of all the synthesized compounds have been inferred from magnetic susceptibility and conductivity measurements, IR, (1)H and (13)C NMR, electronic spectral, mass spectrometry and CHN analysis data. The structure of ligand, 4-{[(E)-(5-bromo-2 hydroxy phenyl)methylidene]amino}-N-(4,6-dimethylpyrimidin-2 yl)benzenesulfonamide has also been determined by X-ray diffraction method. An octahedral geometry has been suggested for all the complexes. The ligands and their metal complexes have been screened for in vitro antibacterial, antifungal and cytotoxic properties. The result of these studies have revealed that all compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against various fungal strains. PMID- 20362359 TI - Design and preparation of aza-analogues of benzo[c]phenanthridine framework with cytotoxic and antiplasmodial activities. AB - Benzo[c]phenanthridine alkaloids represent interesting lead for the discovery of new potential antiplasmodial and/or anticancer drugs. In this field, a novel library of aza-analogs of benzo[c]phenanthroline framework derivatives was designed and prepared. Although these compounds did not have specific antiplasmodial activities, some of them displayed specific in vitro activity against two cancer lines especially compound 24 with an IC(50) against the MCF7 line of 0.6 microM. PMID- 20362360 TI - [A vascular and asymptomatic abnormality]. PMID- 20362361 TI - [Usefulness of JAK2 mutation assessment in recurrent deep venous thrombosis]. AB - The search of JAK2 V617F mutation is a useful tool for the diagnosis of myeloproliferative disorders (MPD). This case report highlights the potential usefulness of this testing in recurrent deep venous thrombosis (DVT) of lower limb. We report a 73-year-old man who presented with three spontaneous episodes of lower limb DVT. The third episode occured while he was receiving fluindione. MPD was suspected because of an increased hematocrit (55 %) and hemoglobin (17g/dl) level. Red cell blood volume was increased and a JAK2 V617F mutation was detected confirming the diagnosis of polycythemia vera. The usefulness of JAK2 mutation for the diagnosis of MPD has been widely demonstrated. Also, some studies confirmed its usefulness in apparently idiopathic abdominal venous thrombosis. This report highlights the possible interest of JAK2 mutation in unexplained recurrent lower limb DVT, especially when it occurs under anticoagulant therapy. PMID- 20362362 TI - [McDuffie hypocomplementemic urticarial vasculitis associated with Sjogren's syndrome]. AB - We report a patient with Sjogren's syndrome who presented with urticarial hypocomplementemic vasculitis. A 46-year-old female was admitted for assessment of ascitis. Clinical examination and computed tomographic scan disclosed evidence of multiple peripheral and intra abdominal lymph nodes. During her admission, she developed several bouts of acute angioedema and urticarial skin lesions. Minor salivary gland biopsy showed focal sialadenitis, stage IV of Chisholm. Schirmer's test was positive. Laboratory examination found low levels of C1q and high levels of C1q antibodies. Therapy with prednisone and hydroxychloroquine was initiated. Six months later, the patient presented with lower limb oedema. Urinalysis showed proteinuria (1g/day) and renal biopsy revealed membranous nephropathy with favorable outcome with corticosteroids. PMID- 20362363 TI - [The pharmacogenetics of vitamin K antagonists: still a matter for discussion]. AB - The use of vitamin K antagonists (VKA) is challenging because of their narrow therapeutic index and a high bleeding risk. These drugs are widely prescribed for the prophylaxis and treatment of many thrombo-embolic disorders. The management of patients with VKA represents a public health problem according to the high number of deaths and hospitalizations in relation to hemorrhagic complications. Monitoring is required because of the large inter-individual variability. The identification of factors, in particular genetic factors, influencing the response to VKA will improve the safety of VKA treatment. In addition to demographic, clinical, biological factors and drug interactions, genetic factors can explain a large part of the inter-individual variability. The main enzyme responsible for VKA metabolism is the hepatic cytochrome P450 2C9 (CYP2C9). Vitamin K epoxide reductase complex subunit I (VKORC1) is a key enzyme in the vitamin K cycle and is the pharmacological target of VKA. Genetic variations affecting both CYP2C9 and VKORC1 are associated with a significant decrease in the VKA dose requirement and an increased risk of bleeding. CYP2C9 and VKORC1 genotyping may identify a subgroup of patients with an early response at the induction of VKA therapy, potentially leading to a high bleeding risk. On the opposite, rare mutations in VKORC1 can explain high dose requirement and pharmacodynamic resistance. Genotyping CYP2C9 and VKORC1 variants before treatment initiation could allow the development of dosing protocols and the identification of patients at high risk of bleeding complications. PMID- 20362364 TI - [Multiple arterial thrombosis in Behcet's disease]. AB - Behcet's disease (BD) is a multisystemic vasculitis. Its etiopathogeny remains unknown. Vascular involvement in BD is frequent and venous thrombosis is the most common manifestation (30% of cases). Arterial involvement is rare (2.7 to 7%). The latter is often severe and considered as a life threatening complication. Pathogenesis of thrombosis occurring in BD remains unclear. We report a 45-year old man, from south of Tunisia, who presented a BD with a bifocal arterial involvement: right internal carotid thrombosis and bilateral proximal thrombosis of the two pulmonary arteries. Therapeutic strategies to address this multiple arterial involvement and the pathogenesis of thrombosis raise many questions. PMID- 20362365 TI - Innovation in clinical learning for the acute hospital environment: nursing grand rounds. AB - The literature reports that workload factors affect nurses' ability to fully engage in continuing professional development. Hence the work environment in acute care calls for innovative approaches to achieve continuous development of nursing practice and work satisfaction. This study employs a one group pre-test post-test design to test the effectiveness of nursing grand rounds on nursing worklife satisfaction and work environment in an acute surgical ward. The effect of nursing grand rounds was measured using the Nursing Worklife Satisfaction Scale and the Practice Environment Scale. There was no change between pre- and post-test on these measures but trends were evident in some component scores. Statistical results were inconclusive but observational data indicated that nursing grand rounds was found to be feasible, well attended with tested processes for implementation in an acute care environment. PMID- 20362366 TI - Evaluation of mentorship programme in nursing education: a pilot study in Turkey. AB - Mentorships increase the students' confidence, help ease the difficulties associated with their new environment and reality, increase self-esteem and help socialize students into the nursing role. The main objective of the programme was to support mentee students in facilitating their transition to the university and nursing. This descriptive, exploratory study was designed using Maslow's hierarchy of needs and a pre/post test Rotter's locus of control. Sixty-two (62) first-year students and fifty-eight (58) fourth-year students were eligible to be in the mentoring programme. Mentors and mentees contacted each other weekly as required to provide information and support. Nursing lecturers were available to support the mentors for regular contact over the 13 weeks of the programme. The data were collected by questionnaire for the first-year and fourth-year students. In addition, in order to determine the efficacy of the mentoring programme, Rotter's Locus of Control Scale was administered to first-year students both at the beginning and the end of the study. The majority of first-year students stated that they benefited from the programme. It was established that the mentoring programme influenced the locus of control positively. The mentoring programme may be used to improve the adaptation of nursing students to both the university and nursing profession. PMID- 20362367 TI - A socio-cultural approach to learning in the practice setting. AB - Practice learning is an essential part of the curriculum and accounts for approximately 60% of the current pre-registration nursing programmes in the Republic of Ireland. The nature and quality of the clinical learning environment and the student nurses' experience of their practice placements is recognised as being influential in promoting the integration of theory and practice. However, the problem experienced by many learners is how to relate their theoretical knowledge to the situation-at-hand within the practice setting. Socio-cultural or activity theories of learning seek to explain the social nature of learning and propose that knowledge and learning are considered to be contextually situated. Lave and Wenger (1991) argue that learning is integrated with practice and through engagement with a community of practice, by means of sponsorship; students become increasingly competent in their identity as practitioners. This paper examines the changes which have occurred within the pre-registration nursing curriculum in the Republic of Ireland with the transition from the apprenticeship system to the graduate programme, and the resulting reduction in clinical learning hours. It also examines the potential impact on the development of student learning with the implementation of the concepts proposed by Lave and Wenger to learning in the practice setting. PMID- 20362368 TI - Assessing methicillin-resistant Staphylococcusaureus knowledge among nursing students. AB - MRSA is becoming more prevalent in healthcare settings and community settings. The purpose of the study is to assess MRSA knowledge among nursing students. A MRSA Survey was administered to nursing students to gauge their general knowledge about MRSA. The scores from the MRSA Survey indicated that nursing students had a knowledge deficit regarding MRSA. Nursing student's need specific MRSA content in the nursing curriculum and need role models in healthcare settings who are following infection control guidelines. A variety of teaching strategies may be used to effectively teach this topic to nursing students. The goal of this education is to prevent the spread of MRSA organisms and decrease the related costs of treating MRSA infections. PMID- 20362369 TI - Nursing students' perceptions of their resources toward the development of competencies in nursing informatics. AB - PURPOSE: This article presents the findings of a doctoral study about the internal and external resources required to develop nursing informatics competencies in student nurses. BACKGROUND: Colleges and universities are responsible for training nursing students, including in the area of nursing informatics. Even though nursing informatics is a specialty recognized by the American Nursing Association (2001), it has received limited attention in Quebec, Canada. METHOD: A total of 131 college-level nursing students were randomly surveyed with a mail questionnaire designed to describe their perceptions about their internal and external resources in nursing informatics. RESULTS: Nursing students perceive that their internal and external resources necessary to ensure "knowledge to act" in nursing informatics is moderately high. They said they lacked knowledge about using spreadsheet programs, presentation software, and courseware, about data security, and about how to analyze the quality of a health related Web site and search electronic scientific databases. CONCLUSION: These results show that, even if nursing students have access to a computer and the Internet at home and even if they feel competent using informatics in nursing, they still lack important resources for developing competencies in nursing informatics. We recommend that faculties and colleges focus on these elements. PMID- 20362370 TI - The nursing programme in the rear-view mirror. Interviews with Swedish nurses one year after their graduation. AB - In order to increase the understanding of how students assimilate the knowledge they need to carry out their professional duties, knowledge about the experience of the nursing education in the light of the first year of employment is important. The aim of this study was to describe nurses' views of their education, one year after their graduation. Interviews with eight nurses, aged 24 to 40 years, were analysed using manifest qualitative content analysis. The results show that, when viewing their education in the rear-view mirror, they emphasised the importance of the applied courses but had started to acknowledge the importance of training in scientific methods, which during their education was seen as less important. They also stated that their training in medical science had been sufficient, although during their education they expressed doubts about whether this level of knowledge would be enough. The nurses also realised that knowledge concerning the subject of nursing science afforded them both opportunities and the potential possibilities to influence nursing care provision. The study indicates that nursing education gives the students the tools they need to perform their assignments as registered nurses, even if clinical experience is required to internalise and consolidate the knowledge. PMID- 20362371 TI - Bioaccumulation and biological effects in the earthworm Eisenia fetida exposed to natural and depleted uranium. AB - The accumulations of both natural (U) and depleted (DU) uranium in the earthworms (Eisenia fetida) were studied to evaluate corresponding biological effects. Concentrations of metals in the experimental soil ranged from 1.86 to 600 mg kg( 1). Five biological endpoints: mortality, animals' weight increasing, lysosomal membrane stability by measuring the neutral red retention time (the NRRT), histological changes and genetic effects (Comet assay) were used to evaluate biological effects in the earthworms after 7 and 28 days of exposure. No effects have been observed in terms of mortality or weight reduction. Cytotoxic and genetic effects were identified at quite low U concentrations. For some of these endpoints, in particular for genetic effects, the dose (U concentration)-effect relationships have been found to be non-linear. The results have also shown a statistically significant higher level of impact on the earthworms exposed to natural U compared to depleted U. PMID- 20362372 TI - TMJ arthroscopy: rare neurological complications associated with breach of the skull base. AB - We report an interesting case of vertigo and palsies of the right oculomotor and trochlear nerves associated with fluid collection in the region of the ipsilateral temporal lobe and cavernous sinus after bilateral arthroscopy of the temporomandibular joint (TMJ). PMID- 20362373 TI - Stepping with an ankle foot orthosis re-examined: a mechanical perspective for clinical decision making. AB - BACKGROUND: Ankle foot orthoses are used to stabilize the ankle joint and aid toe clearance during stepping in persons after incomplete spinal cord injury. However, little is known about kinematics and kinetics of stepping with an orthosis during the transition from stance-to-swing and swing-to-stance. We intended to examine if an ankle foot orthosis impeded or facilitated optimal ankle, knee and hip joint kinematics, kinetics and spatiotemporal parameters during the transition phases of normal walking. METHODS: Fourteen healthy participants walked on a split-belt instrumented treadmill with and without a posterior leaf spring ankle foot orthosis at 1.2m/s. Three dimensional motion data and ground reaction forces were captured during 30-second trials of steady state walking. FINDINGS: During stance-to-swing, the orthosis significantly decreased hip extension [8.6 (5.5) to 6.7 (5.5) degrees, P=0.001], ankle plantarflexion [19.4 (5.7) to 12.0 (5.2) degrees, P<0.001] and plantarflexor power [0.18 (0.03) to 0.15 (0.03) watts/body weight, P<0.001]. During swing-to stance, the orthosis significantly increased hip flexion [32.7 (4.7) to 35.6 (5.1) degrees, P=0.028] and ankle plantarflexion [8.4 (3.5) to 10.9 (4.7) degrees, P<0.001] and decreased loading rate [0.06 (0.01) to 0.05 (0.01) N/kg, P=0.018] and braking force [0.16 (0.02) to 0.15 (0.02) N/kg, P=0.013]. Double limb support time increased significantly with the orthosis [0.19 (0.02) to 0.22 (0.03) seconds, P<0.000]. INTERPRETATION: An ankle foot orthosis affected joint kinematics and kinetics during the transition from stance-to-swing and vice versa. The use of orthosis to improve transition phase kinematics and kinetics in individuals with incomplete spinal cord injury warrants assessment. PMID- 20362374 TI - Movement characteristics of upper extremity prostheses during basic goal-directed tasks. AB - BACKGROUND: After an upper limb amputation a prosthesis is often used to restore the functionality. However, the frequency of prostheses use is generally low. Movement kinematics of prostheses use might suggest origins of this low use. The aim of this study was to reveal movement patterns of prostheses during basic goal directed actions in upper limb prosthetic users and to compare this with existing knowledge of able-bodied performance during these actions. METHODS: Movements from six users of upper extremity prostheses were analyzed, three participants with a hybrid upper arm prosthesis, and three participants with a myoelectric forearm prosthesis. Two grasping tasks and a reciprocal pointing task were investigated during a single lab session. Analyses were carried out on the kinematics of the tasks. FINDINGS: When grasping, movements with both prostheses showed asymmetric velocity profiles of the reach and had a plateau in the aperture profiles. Reach and grasp were decoupled. Kinematics with the prostheses differed in that the use of upper arm prostheses required more time to execute the movements, while the movements were less smooth, more asymmetric, and showed more decoupling between reach and grasp. The pointing task showed for both prostheses less harmonic movements with higher task difficulty. INTERPRETATION: Characterizing prosthetic movement patterns revealed specific features of prosthetic performance. Developments in technology and rehabilitation should focus on these issues to improve prosthetic use, in particular on improving motor characteristics and the control of the elbow, and learning to coordinate the reach and the grasp component in prehension. PMID- 20362375 TI - Arsenic transfer and impacts on snails exposed to stabilized and untreated As contaminated soils. AB - An As-contaminated soil (Unt) was amended with either iron grit (Z), a coal fly ash (beringite, B) or B + Z (BZ) and placed in lysimeters in 1997. An uncontaminated soil (R) was also studied. In summer and autumn 2003, lettuces were cultivated in the lysimeters and snails were caged for one month. Lettuce As concentrations were higher during the summer, while no differences occurred in snails between seasons. Snail As concentrations (microg g(-1) DW) ranged from 2.5 to 7.0 in B, Z and BZ, and peaked at 17.5 in Unt. In summer, snail survival was affected in Unt and Z compared to R and B while no mortality was noticed in autumn. Snail growth decreased only in B, BZ and Unt in autumn. Snail As concentrations suggest a risk for their predators even on the remediated soils. PMID- 20362376 TI - Distribution and trends of mercury in deciduous tree cores. AB - The distribution of total mercury (THg) within common deciduous trees and the applicability of tree cores as biomonitors of historical environmental THg trends were assessed for both contaminated and reference sites around Kingston, Ontario. Samples were collected from Acer spp., Quercus spp. Populus spp. and Salix spp. Bark and wood THg concentrations were found to be highly correlated whereas soil and wood THg concentrations were not. There were no temporal relationships for THg in dated tree rings corresponding with any other known environmental Hg trends. The shoreline species, Populus and Salix spp., had the greatest bark and wood Hg concentrations reaching 18 ng/g, significantly higher than for inland trees Quercus and Acer spp. with maximum values of 7 and 1.2 ng/g for bark and wood respectively. While tree cores cannot be reliably used as temporal THg biomonitors, there is promise for tree species such as Populus spp and Salix spp as spatial indicators of local long-term Hg contamination. PMID- 20362377 TI - Understanding the association between condom use at first and most recent sexual intercourse: an assessment of normative, calculative, and habitual explanations. AB - The aim of this study was to provide a better understanding of the likely mechanisms underlying regular condom use. In 2009, 1145 sexually active individuals aged 18-65 years were surveyed online, after being recruited via an e mail message circulated at a large Croatian university and posted on various social networking websites. Participants' mean age was 28.1 years (SD = 8.01). Women constituted a slight majority of the sample (51.6%). The research questions - whether the frequently observed association between condom use at first and most recent sexual intercourse could be best predicted by (a) norm-oriented behavior; (b) calculative decision-making; or (c) habit formation - were tested using multiple logistic regression. Only the calculative and habitual motivational determinants of condom use were significant predictors. Unlike calculative use, which decreased the odds of condoms being used at both occasions, habitual use, as expected, increased the odds of condom use. In addition, the habitual modality of condom use significantly predicted consistent condom use with both casual and steady sexual partners. Age, being in a relationship, and the number of lifetime sexual partners were negatively associated with habitual condom use. The finding that habit plays a substantial role in consistent condom use suggests the need for further exploration of personality and relational factors associated with the initiation of habitual condom use. PMID- 20362378 TI - Will teaching social sciences to medical students hasten health care reform? A commentary on Sales and Schlaff. PMID- 20362379 TI - Internalization of stigma for parents of children with autism spectrum disorder in Hong Kong. AB - An attribution model was tested to explain the internalization of stigma among parents of children with Autism Spectrum Disorder (ASD). In the model, the internalization paths from courtesy stigma to affiliate stigma and the impact of three types of social support on affiliate stigma and psychological well-being were examined. The study was conducted in Hong Kong, China; one hundred and eighty-eight parents of children with ASD were recruited to complete the questionnaire. The model showed excellent fit to the data. Path analysis suggested three possible paths of internalizing courtesy stigma, including the direct path to affiliate stigma, through perceived controllability, or through perceived responsibility and self-blame. Support from family, significant others, friends, or professionals was found to be related to affiliate stigma and psychological well-being differentially. The internalization of stigma among parents of ASD children was severe. The path model sheds light on possible ways to reduce stigma in future services. PMID- 20362380 TI - Individual, social and environmental correlates of physical activity among women living in socioeconomically disadvantaged neighbourhoods. AB - Women living in socioeconomically disadvantaged neighbourhoods are at heightened risk for physical inactivity, but little is known about the correlates of physical activity among this group. Using a social-ecological framework, this study aimed to determine the individual, social and neighbourhood environmental correlates of physical activity amongst women living in such neighbourhoods. During 2007-2008 women (n = 4108) aged 18-45 years randomly selected from urban and rural neighbourhoods of low socioeconomic status in Victoria, Australia completed the International Physical Activity Questionnaire (long). They reported on individual (self-efficacy, enjoyment, intentions, outcome expectancies, skills), social (childcare, social support from family and friends/colleagues, dog ownership) and neighbourhood environmental (neighbourhood cohesion, aesthetics, personal safety, 'walking environment') factors. Multinomial logistic regression was used to examine the odds of increasing categories of leisure time physical activity (LTPA) and transport-related physical activity (TRPA) for each individual, social and environmental factor. In partially adjusted analyses, all individual, social and environmental variables were positively associated with LTPA, while all individual factors, family and friend support and the walking environment were positively associated with TRPA. In fully adjusted multivariable models, all individual and social factors remained significantly associated with LTPA, while self-efficacy, enjoyment, intentions, social support, and neighbourhood 'walking environment' variables remained significantly associated with TRPA. In conclusion, individual and social factors were most important for LTPA, while individual, social and neighbourhood environmental factors were all associated with TRPA. Acknowledging the cross-sectional design, the findings highlight the importance of different levels of potential influence on physical activity in different domains, which should be considered when developing strategies to promote physical activity amongst women living in socioeconomically disadvantaged neighbourhoods. PMID- 20362381 TI - 'Like sugar and honey': the embedded ethics of a larval control project in The Gambia. AB - This paper describes a malaria research project in The Gambia to provoke thinking on the social value of transnational research. The Larval Control Project (LCP) investigated the efficacy of a microbial insecticide to reduce vector density and, ultimately, clinical malaria in Gambian children. The LCP's protocol delineated a clinical surveillance scheme that involved Village Health Workers (VHWs) supported by project nurses. Combining insights from ethnographic fieldwork conducted at the Medical Research Council (MRC) Laboratories in Farafenni from 2005 to 2009, open-ended interviews with project nurses, and eight focus group discussions held with participant mothers in October 2007, we consider the social impact of the LCP's investigative method against the backdrop of several years of research activity. We found that while participants associated the LCP with the clinical care it provided, they also regarded the collaboration between the nurses and VHWs added additional benefits. Organised around the operational functions of the trial, small-scale collaborations provided the platform from which to build local capacity. While ethical guidelines emphasise the considerations that must be added to experimental endeavour in southern countries (e.g. elaborating processes of informed consent, developing strategies of community engagement or providing therapeutic access to participants after the trial concludes), these findings suggest that shifting attention from supplementing ethical protocols to the everyday work of research embedding ethics through scientific activity - may provide a sounder basis to reinforce the relationship between scientific rigour and social value. PMID- 20362382 TI - Estimating the costs of medicalization. AB - Medicalization is the process by which non-medical problems become defined and treated as medical problems, usually as illnesses or disorders. There has been growing concern with the possibility that medicalization is driving increased health care costs. In this paper we estimate the medical spending in the U.S. of identified medicalized conditions at approximately $77 billion in 2005, 3.9% of total domestic expenditures on health care. This estimate is based on the direct costs associated with twelve medicalized conditions. Although due to data limitations this estimate does not include all medicalized conditions, it can inform future debates about health care spending and medicalization. PMID- 20362383 TI - Non-technical skills for obstetricians conducting forceps and vacuum deliveries: qualitative analysis by interviews and video recordings. AB - OBJECTIVE: Non-technical skills are cognitive and social skills required in an operational task. These skills have been identified and taught in the surgical domain but are of particular relevance to obstetrics where the patient is awake, the partner is present and the clinical circumstances are acute and often stressful. The aim of this study was to define the non-technical skills of an operative vaginal delivery (forceps or vacuum) to facilitate transfer of skills from expert obstetricians to trainee obstetricians. STUDY DESIGN: Qualitative study using interviews and video recordings. The study was conducted at two university teaching hospitals (St. Michael's Hospital, Bristol and Ninewells Hospital, Dundee). Participants included 10 obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries. Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting forceps and vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by the three researchers and then compared for consistency of interpretation. The experts reviewed the coded data for respondent validation and clarification. The themes that emerged were used to identify the non-technical skills required for conducting an operative vaginal delivery. RESULTS: The final skills list was classified into seven main categories. Four categories (situational awareness, decision making, task management, and team work and communication) were similar to the categories identified in surgery. Three further categories unique to obstetrics were also identified (professional relationship with the woman, maintaining professional behaviour and cross-monitoring of performance). CONCLUSION: This explicitly defined skills taxonomy could aid trainees' understanding of the non-technical skills to be considered when conducting an operative vaginal delivery and potentially reduce morbidity and improve the experience of delivery for the mother. PMID- 20362384 TI - Hypertension in pregnancy: think laterally. PMID- 20362385 TI - ERSPC and PLCO prostate cancer screening studies: what are the differences? PMID- 20362386 TI - Impact of posterior musculofascial reconstruction on early continence after robot assisted laparoscopic radical prostatectomy: results of a prospective parallel group trial. AB - BACKGROUND: A significant proportion of patients develop urinary incontinence early after radical prostatectomy. Posterior reconstruction of supporting tissues has been found to reduce incontinence in open and conventional laparoscopic prostatectomy series. OBJECTIVE: To investigate whether our version of a posterior musculofascial reconstruction will reduce early incontinence and have a beneficial effect on patients' quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: One hundred seven consecutive patients undergoing primary robot assisted radical laparoscopic prostatectomy (RALP) performed by a single surgeon at one tertiary referral oncology institution were alternately assigned (not randomised) to intervention (n=53) or control groups (n=54). SURGICAL PROCEDURE: RALP with median fibrous raphe reconstruction (MFRR) followed by formation of the urethrovesical anastomosis (intervention group) versus standard anastomosis without posterior reconstruction (control group). MEASUREMENTS: Measurements included incontinence at baseline and 3-mo intervals; QoL as measured by a simple questionnaire, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), and Prostate Cancer Module (PR25) questionnaires preoperatively and at 6 mo postprocedure; tumour characteristics; operative time; fascial preservation score; duration of catheterisation; and anastomotic leakage on cystogram. RESULTS AND LIMITATIONS: For intervention and control groups respectively, mean catheter duration was 11.74 d and 12.74 d (p=0.451); leakage on cystogram was present in six and eight cases (p=0.28); and incontinence (any involuntary urine loss) at 3 mo was 75% and 69% (p=0.391) and at 6 mo was 51% and 43% (p=0.686). Urinary retention occurred only in one case (control group). The percentage of cases returning to baseline in all QoL domains (except insomnia) was similar at 6 mo between the two groups. Short follow-up, lack of blinding, and probable small differences in our method of MFRR performed compared with other studies were identified as significant limitations. CONCLUSIONS: No significant difference in any of the analysed outcome measures was observed. Posterior reconstruction of the musculofascial complex does not appear to improve early urinary incontinence after RALP. PMID- 20362387 TI - Re: Antonio Rosales, Jose T. Salvador, Guillermo Udaneta, et al. Laparoscopic kidney transplantation. Eur Urol 2010;57:164-7. PMID- 20362388 TI - Therapy of MS. AB - The era of disease-modifying drugs (DMDs) in multiple sclerosis (MS) treatment began in the 1990s, first with interferon-beta (IFNbeta), and the number of agents has increased steadily since then. Currently, there are six different parenteral formulations approved for MS treatment and many other oral and parenteral ones are in different stages of investigation or awaiting approval by federal agencies. All of these medications have demonstrated partial efficacy along with different side effect profiles. Increasing our understanding about the natural behaviour of MS and its different types and stages, diversity of different therapies, their strength and weaknesses, and their serious and sometimes life-threatening side effects have created challenges for treating physicians; making the choice of individualized optimal treatment increasingly more complicated. In this review, we will summarize present and future treatment options and also address clinical challenges we are regularly facing in arriving at treatment choices for our patients. PMID- 20362390 TI - Metal ion removal from aqueous solution using physic seed hull. AB - The potential of physic seed hull (PSH), Jantropha curcas L. as an adsorbent for the removal of Cd(2+) and Zn(2+) metal ions from aqueous solution has been investigated. It has been found that the amount of adsorption for both Cd(2+) and Zn(2+) increased with the increase in initial metal ions concentration, contact time, temperature, adsorbent dosage and the solution pH (in acidic range), but decreased with the increase in the particle size of the adsorbent. The adsorption process for both metal ions on PSH consists of three stages-a rapid initial adsorption followed by a period of slower uptake of metal ions and virtually no uptake at the final stage. The kinetics of metal ions adsorption on PSH followed a pseudo-second-order model. The adsorption equilibrium data were fitted in the three adsorption isotherms-Freundlich, Langmuir and Dubinin-Radushkevich isotherms. The data best fit in the Langmuir isotherm indication monolayer chemisorption of the metal ions. The adsorption capacity of PSH for both Zn(2+) and Cd(2+) was found to be comparable with other available adsorbents. About 36 47% of the adsorbed metal could be leached out of the loaded PSH using 0.1M HCl as the eluting medium. PMID- 20362389 TI - Induction of cell death in neuroblastoma by inhibition of cathepsins B and L. AB - A specific irreversible inhibitor of both cathepsins B and L, Fmoc-Tyr-Ala-CHN(2) (FYAD) induced apoptosis of neuroblastoma cells but not other tumor cells. Cysteine protease inhibitors that were not efficient inhibitors of both proteases did not cause death of any cell line tested. Apoptosis was preceded by accumulation of large electron dense vesicles and multivesicular bodies in the cytoplasm. Exposure of cells to the cathepsin D inhibitor, pepstatin, failed to rescue cells from FYAD-induced death. These results indicate that inhibition of cathepsins B and L may provide a unique mechanism for selectively inducing death of neuroblastoma with limited toxicity to normal cells and tissues. PMID- 20362391 TI - Characteristics and mechanisms of Cu(II) biosorption by disintegrated aerobic granules. AB - Disintegrated aerobic granules (DAG) as an effective biosorbent had great potential to remove Cu(II) from aqueous solution. The effects of solution pH value, contact time, initial Cu(II) concentration on the biosorption were investigated. Kinetic studies indicate that pseudo-second-order model with correlation coefficients of 0.9999 best fits the Cu(II) biosorption process. Investigation of the biosorption mechanisms shows that Cu(II) biosorption is associated with a significant release of Ca(II). The adsorption capacity of extracted extracellular polymeric substances (EPS) was 2.34 times as much as that of pristine DAG, indicating the significant role of EPS in adsorption. In order to determine the role of different functional groups, DAG was chemically modified to block specific functional groups and was then used in the adsorption of Cu(II). The anionic carboxyl group, was identified as the key binding site for the cationic Cu(II). Results reveal that ion exchange is the most important biosorption mechanism but other mechanisms to some extent like electrostatic interaction, involving in functional groups, also play a part. PMID- 20362392 TI - The reduction of formaldehyde and VOCs emission from wood-based flooring by green adhesive using cashew nut shell liquid (CNSL). AB - To discuss the reduction of formaldehyde and volatile organic compound (VOC) emissions from engineered flooring, cashew nut shell liquid (CNSL)-formaldehyde (CF) resin and CF/PVAc resin were applied for the maple face of the veneer bonding on plywood. The CF resin was used to replace urea-formaldehyde (UF) resin in the formaldehyde-based resin system in order to reduce formaldehyde and VOC emissions from the adhesives used between the plywoods and fancy veneers. For the CF/PVAc resins, 5, 10, 20 or 30% of PVAc was added to the CF resin. The CF/PVAc resins showed better bonding than the commercial natural tannin adhesive with a higher level of wood penetration. The standard formaldehyde emission test and a VOC analyzer were used to determine the formaldehyde and VOC emissions, respectively, from the engineered floorings. The CF resin and CF/PVAc resin systems with UV coating satisfied the E(1) and E(0) grades of the Korean Standard. TVOC emission was slightly increased by the PVAc addition. PMID- 20362393 TI - Preparation of a new chromium(III) selective electrode based on 1-[(2-hydroxy ethyl) amino]-4-methyl-9H-thioxanthen-9-one as a neutral carrier. AB - A new chromium carbon paste electrode sensor based on a carbon paste electrode containing 1-[(2-hydroxy ethyl) amino]-4-methyl-9H-thioxanthen-9-one (AMTX) as new carrier has been prepared. The influence of carbon paste ingredients including sodium tetraphenylborate (NaTPB), ionophore, Nujol and graphite powder on the electrode response has been investigated. The best performance characteristics for the electrode was obtained with a carbon:NaTPB:Nujol:AMTX in the mass ratio of (400:1.43:57.2:3mg) (86.65:0.31:12.39:0.65%). At the optimum value of all variables, the response of electrode is linear in range of 3.2x10( 7) to 1.0x10(-1)mol L(-1) with a Nernstian slope of 20.51 mV decade(-1) of Cr(3+) ion concentration with detection limit of 1.6x10(-7)mol L(-1). The electrode response is independent of pH in the range of 4.8-6.3, while the response time of the electrode was approximately 8 s. The potentiometric selectivity coefficients of proposed chromium-selective electrode towards various interfering ions were determined by fixed interference method (FIM), separate solution method (SSM) and matched potential method (MPM). PMID- 20362394 TI - Active carbon-ceramic sphere as support of ruthenium catalysts for catalytic wet air oxidation (CWAO) of resin effluent. AB - Active carbon-ceramic sphere as support of ruthenium catalysts were evaluated through the catalytic wet air oxidation (CWAO) of resin effluent in a packed-bed reactor. Active carbon-ceramic sphere and ruthenium catalysts were characterized by N(2) adsorption and chemisorption measurements. BET surface area and total pore volume of active carbon (AC) in the active carbon-ceramic sphere increase with increasing KOH-to-carbon ratio, and AC in the sample KC-120 possesses values as high as 1100 m(2) g(-1) and 0.69 cm(3) g(-1) (carbon percentage: 4.73 wt.%), especially. Active carbon-ceramic sphere supported ruthenium catalysts were prepared using the RuCl(3) solution impregnation onto these supports, the ruthenium loading was fixed at 1-5 wt.% of AC in the support. The catalytic activity varies according to the following order: Ru/KC-120>Ru/KC-80>Ru/KC-60>KC 120>without catalysts. It is found that the 3 wt.% Ru/KC-120 catalyst displays highest stability in the CWAO of resin effluent during 30 days. Chemical oxygen demand (COD) and phenol removal were about 92% and 96%, respectively at the reaction temperature of 200 degrees C, oxygen pressure of 1.5 MPa, the water flow rate of 0.75 L h(-1) and the oxygen flow rate of 13.5 L h(-1). PMID- 20362395 TI - Stability studies of double-base propellants with centralite and malonanilide stabilizers using MO calculations in comparison to thermal studies. AB - Propellants containing nitrate esters need stabilizers to avoid early decomposition or even explosion during storage. Newly prepared malonanilides M1 M5 were tested in stabilizing double-base propellants (DBPs). Their stabilization was compared with the effect of classical stabilizer N,N'-diethyldiphenyl urea (C1) using both practical thermal stability tests (qualitative and quantitative tests) and theoretical molecular orbital calculations. This research shows that the new stabilizers (malonanilides) have good stabilizing effects. Some of malonanilides e.g. (M5) and (M2) have higher stability effects. Different mechanisms were suggested to explain the role of different stabilizers. Molecular orbital calculations using the semi-empirical program AM1 are performed on the new and classical stabilizers. Correlation was made between the volume (ml) of NO(x), weight loss (wt%), other thermal analyses data, calculated thermodynamic parameters like activation energy (E(a), kJ mol(-1)) of the decomposed propellant samples containing different stabilizers and some of their calculated properties such as HOMO, LUMO energies, the charge distribution and the pi-bond order. The stabilization effect decreases with the increase in HOMO energy. The correlation between the net charge and parameters measured for the stabilization effect shows good accordance. Comparison of the results obtained show that the high electron charge on N atom of the stabilizers and on its benzene ring is the most important factor, but not the only factor governing the stabilization effect of the stabilizers. PMID- 20362396 TI - Photo-induced fluorescence of magnesium derivatives of tetracycline antibiotics in wastewater samples. AB - An analytical strategy, for the determination of tetracyclines (TCs), based on a HPLC system coupled with a photo-reactor followed by post-column derivatization was developed. Higher fluorescence emission after coupling the resulting photo fragments with magnesium ions was observed for the determination of minocycline (MC), epitetracycline (ETC), tetracycline (TC) and doxycycline (DC). The manifold included a HPLC system with a photo-reactor (PTFE tubing helically coiled around a low-pressure mercury lamp), a mixing T-piece and a fluorescence detector. The derivatization reagent was delivered at 0.5 mL min(-1) by a pump. After HPLC separation using a gradient system with a mobile phase containing oxalic acid 0.02 M and acetonitrile, TCs were irradiated for 60 s, and the resulting photo fragments were mixed with the post-column derivatization reagent, and the magnesium derivatives of TCs were detected by fluorimetry (lambda(exc) 386 nm, lambda(em) 500 nm). The results obtained showed a significant increase of sensitivity due to photodegration of TCs, 45.4%, 37.6% and 25.3% for MC, TC and ETC respectively. For DC an increase of only 1.5% was observed. The developed method was successfully applied to TCs determination in hospital and municipal wastewater samples using solid phase extraction with Oasis HLB cartridges. The LOQs were 0.25, 0.15, 01 and 0.25 microg L(-1) for TC, ETC, MC and DC, respectively. The recovery values oscillated between 107.1% and 92.4% for fortification of 2.5 microg L(-1) of each antibiotic. PMID- 20362397 TI - Is there a role for benzodiazepines in the management of lumbar disc prolapse with acute sciatica? AB - Patients with acute lumbar disc prolapse with sciatica who are not considered candidates for surgery are usually treated with physiotherapy and non-steroidal anti-inflammatory agents. Moreover, the treatment with benzodiazepines is common practice in the absence of class I or II level of evidence. Here we assessed the role of benzodiazepines in the conservative management of acute lumbar disc prolapse. Using a placebo-controlled, double-blinded design, 60 patients were randomized to receive placebo or diazepam in addition to mechanical physiotherapy and analgesics for the first 7 days of conservative treatment of clinically and radiologically confirmed lumbar disc prolapse. The primary objective was to evaluate if physiotherapy plus analgesics, but without benzodiazepines, is equivalent to the same therapy plus benzodiazepines. The primary endpoint was centralization of referred pain at day 7. Twenty-six female and 34 male patients were enrolled. The median age was 42 years (range 22-68 years). Analysis of the primary endpoint demonstrated equivalence between placebo and diazepam (median 60% vs. 50% reduction of distance of referred pain at day 7) within the predefined equivalence tolerance of 20% at a significance level of p<0.05. Regarding the secondary endpoints, the median duration of the stay in hospital was shorter in the placebo arm (8 vs. 10 days, p=0.008), and the probability of pain reduction on a visual analog scale by more than 50% was twice as high in placebo patients (p<0.0015). Benzodiazepines should not be used routinely in patients treated with mechanical physiotherapy for lumbar disc prolapse. PMID- 20362398 TI - Reduction of plasma granzyme A correlates with severity of sepsis in burn patients. AB - The risk of mortality is high in burn patients and correlates with age, burn area extent, and sepsis. Immunosuppression has been reported to occur after severe burn. Cytotoxic cells possess specialized granules containing perforin and a group of serine proteases (granzymes). Granzyme A is a serine protease constitutively expressed by gammadelta and NK cells, in agreement with their functional cytolytic potential. In vitro studies have shown that GrA may be released extracellularly during cytotoxic cell degranulation, indicating the activation of cytotoxic cells. The aim of our study was to determine plasma GrA activity in burned patients and to verify if decreased GrA levels were associated with poor prognosis. Specific GrA activity was tested in the plasma of burned and healthy subjects by esterase assay. Plasma GrA was significantly decreased in septic rather than in nonseptic burn patients and in healthy subjects (p < 0.05 and p < 0.001, respectively). At day 3 plasma GrA was significantly lower in nonsurvivor than in survivor septic patients (p < 0.05). The value of 91 mOD showed a sensitivity of 100% and a specificity of 84% in differentiating survivor from nonsurvivor septic patients. Because this is a retrospective study, Granzyme A is not a confirmed predictor of septic outcome after burn, but its determination could give useful information about the development and severity of sepsis. PMID- 20362399 TI - Practical management of the burnt patient with epidermolysis bullosa. PMID- 20362400 TI - Treatment of post-burn neuropathic pain: evaluation of pregablin. AB - Burn survivors have described a type of pain, usually after wound healing, that has characteristics of neuropathic pain. This pain is not well treated with conventional medications. Pregabalin has had reported success in treating diabetic and post-herpetic neuropathic pain. We report our experience with pregabalin for the treatment of post-burn neuropathic pain. A retrospective review of patients treated with pregabalin in a burn outpatient clinic was undertaken. A numerical pain scale was administered to each patient prior to and after treatment to determine efficacy. Side effects and reasons for discontinuation were noted. Out of 24 patients 4 patients were lost to followup, 5 patients discontinued taking pregabalin and 2 patients had incomplete data for evaluation. Of the remaining 13 patients, 69% (11) had a reduction in pain score after treatment. In addition, 2 of the patients who discontinued use had a pain score which decreased to 0. Pregabalin is a well-tolerated, effective means of treating post-burn neuropathic pain. Time to achieve effective dosing is relatively quick and there is a range of dosing available. The mechanism, pharmacokinetic benefits, and potential benefits are discussed. Further studies will be needed to look effects on quality of life and reduction of opioid use. PMID- 20362401 TI - Online adaptive replanning method for prostate radiotherapy. AB - PURPOSE: To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. METHODS AND MATERIALS: The new "SAM+SWO" scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. RESULTS: For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 +/- 2 minutes. CONCLUSION: The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT. PMID- 20362402 TI - Value of intensity-modulated radiotherapy in Stage IV head-and-neck squamous cell carcinoma. AB - PURPOSE: To review outcome and toxicity of Stage IVa and IVb head-and-neck squamous cell carcinoma patients treated with concomitant chemotherapy and intensity-modulated radiotherapy (IMRT) according to a hybrid fractionation schedule. METHODS AND MATERIALS: Between 2006 and 2008, 42 patients with Stage IV head-and-neck squamous cell carcinoma were irradiated according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. Chemotherapy (cisplatinum, 100 mg/m(2)) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 55), treated according to the same schedule, but without intensity modulation. RESULTS: Locoregional control (LRC) and overall survival were 81% and 56% after 2 years, respectively. In comparison with the previous cohort, no significant differences were observed regarding either LRC (66%, p = 0.38) or overall survival (73%, p = 0.29). No Grade 4 or 5 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of late Grade 2 or 3 xerostomia (52.9% vs. 90.2%, p < 0.001). No difference was observed regarding late Grade 2 or 3 dysphagia (p = 0.66). CONCLUSIONS: Intensity-modulated chemoradiotherapy does not compromise LRC and significantly reduces late toxicity, especially regarding xerostomia. PMID- 20362403 TI - [Bleeding in the first trimester of pregnancy: diagnostic approach and therapeutic management]. PMID- 20362404 TI - Genetic and antigenic characterization of foot-and-mouth disease viruses isolated in Taiwan between 1998 and 2009. AB - A devastating outbreak of foot-and-mouth disease (FMD), caused by a porcinophilic serotype O virus, occurred in Taiwan in March 1997. This outbreak was brought under control by means of a stamping-out policy and vaccination. Although mandatory vaccination was conducted in Taiwan between 1997 and 2007, sporadic outbreaks of FMD occurred between 1998 and 2009; however, the viruses that caused these outbreaks remain uncharacterized. This article reports the genetic and antigenic characterization of FMD viruses isolated in Taiwan during this period. Sequence analysis of the VP1 coding region showed that the viruses isolated in Taiwan between 1998 and 2009 were most similar to viruses isolated in Taiwan in 1997 and to viruses isolated from Hong Kong and Vietnam in 1991-1996. The results of phylogenetic analysis suggested that the viruses isolated in Taiwan in 1998 2009 were derived from the viruses isolated in Taiwan in 1997. However, substantial mutations were found in the viruses isolated in 2009, and some of these changes may have resulted from vaccine pressure in the field. Serum neutralization tests confirmed that viruses isolated in 2009 showed a significant change in antigenicity. This is the first report of changes in the VP1 sequence and antigenicity of porcinophilic FMD viruses isolated from an area in which long term mandatory vaccination against FMD was practiced. PMID- 20362405 TI - Analysis of the biosynthesis genes and chemical components of the capsule of Avibacterium paragallinarum. AB - The aim of this study was to investigate biosynthesis genes and chemical components of the capsule of Avibacterium paragallinarum. The sequence of a 10-kb region containing the capsule biosynthetic locus of Av. paragallinarum was determined. Two reference strains, i.e., 221 (serovar A) and H18 (serovar C), together with four Taiwanese field strains (all serovar C) were sequenced. The results showed that there are two genotypes (I and II) of the capsule biosynthetic locus in Av. paragallinarum, and the capsule genotype is independent of the serovar. The capsule biosynthetic loci of genotypes I and II consisted of six and five genes, respectively. The genotype I genes encoded proteins that are most similar to proteins from Pasteurella multocida capsule types A and F while the genotype II genes encoded proteins most similar to proteins from P. multocida capsule type D and Escherichia coli K5. The results suggested that genotype I strains contain hyaluronan or chondroitin in the capsule wall while genotype II contain heparosan. Enzymatic digestion of the capsule materials extracted from Av. paragallinarum showed that genotype I strains contained chondroitin while genotype II strains contained heparosan in the capsule. This is the first report on the existence of different genotypes of capsule biosynthesis genes in Av. paragallinarum and the presence of chondroitin and heparosan as chemical components of the capsule of Av. paragallinarum. PMID- 20362406 TI - In the absence of dental records, do we need forensic odontologists at mass grave sites? AB - With the exception of exhumations of mass graves in Latin America, forensic dentists and odontologists are rarely involved in the examination of mortal remains recovered from mass graves. The cited reason is often that "there are no dental records-so what is the point"? In this presentation we review the published accounts of examination of remains arising from the conflict in the former Yugoslavia between 1991 and 1999 in which dental examinations are reported. There are roughly 30,000 missing persons of which more than 15,000 mortal remains have been identified, mostly based on DNA. There are 9 sources which describe postmortem dental examinations of 3919 sets of remains; of these, 23% were purported to have been identified specifically from dental information. Of the 8100 listed missing persons from the Srebrenica mass killings in 1995, we located 600 dental records. A sample of 263 charts was examined for information about first molar treatment as we are concerned that dental charting of individuals who lose their first molars may be incorrectly done if allowance is not made for mesial drift of the remaining molars. We found that of all the first molar extractions that are ever going to occur according to these dental charts, 63% have taken place by age 18. The majority of extracted first molars have a functional age of 17 years. We observe that an adult's remains from Srebrenica usually have only second and third molars, which have often drifted forward to occupy the position of the first molar creating the appearance of third molar agenesis. We conclude: that, since dental identifications of victims in mass graves and mass disasters is the exception rather than the rule, even in the absence of DNA-based identifications, international forensic odontologists have an ethical obligation to become more involved in examination of mass grave victims, that there must be more determined searches for antemortem dental records; that local dentists should be approached to participate in the examination of remains and lastly that dental examination and charting by anthropologists and pathologists may be grossly inaccurate. Furthermore, even in the absence of dental records, there is significant information about the individual to be obtained by an oral biologist since many families have useful memories about the oral status of their loved ones who went missing. PMID- 20362407 TI - Subtyping of substance use disorders in a high-risk welfare-to-work sample: a latent class analysis. AB - The goals of this study were (a) to investigate the existence of substance abuse/dependence subtypes in a diverse low-income welfare to work sample and (b) to explore subtype differences in rates of comorbid psychiatric and medical conditions. Data for all demographic and clinical variables were extracted from deidentified case records of 4,977 clients enrolled in a comprehensive case management program for welfare recipients with substance use disorders. Latent class analysis supported a five-class model made up of a multiple abuse/dependence class (n = 1,133), a cocaine/alcohol class (n = 2,120), an opioids class (n = 1,346), a cannabis class (n = 362), and a small polysubstance/none primary class (n = 16). Post hoc chi-square analyses revealed several between-class differences, perhaps reflecting differing levels of severity and service needs. All five classes were characterized by high rates of medical and psychiatric comorbidity. PMID- 20362408 TI - High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha 2a (40KD) (PEGASYS) and once-daily ribavirin. AB - This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting. PMID- 20362409 TI - Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. AB - The purpose of this study was to investigate the effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Diosmin was administered to streptozotocin-induced (45 mg/kg b.w) diabetic rats at different doses (25, 50, 100 mg/kg b.w) for 45 days to assess its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin and carbohydrate metabolic enzymes, it was found that plasma glucose was significantly reduced in a dose-dependent manner when compared to the diabetic control. In addition, oral administration of diosmin (100mg/kg b.w) significantly decreased glycosylated hemoglobin and increased hemoglobin and plasma insulin. The activities of the hepatic key enzymes such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased whereas, glucose-6 phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, protection against body weight loss of diabetic animals was also observed. These results showed that diosmin has potential antihyperglycemic activity in streptozotocin-nicotinamide-induced diabetic rats. PMID- 20362410 TI - [The history of Saint-Martin and Beaumont]. PMID- 20362411 TI - Double-contrast magnetic resonance imaging in preoperative evaluation of rectal cancer: use of aqueous jelly as luminal contrast. PMID- 20362412 TI - The compressAR StrongArm 6000XL for hemostasis in day-case peripheral angioplasty patients: our initial experience. PMID- 20362413 TI - Intuitive numeric rating scale to measure performance status in cancer patients. PMID- 20362414 TI - Assessing child and adolescent anxiety in psychiatric samples with the Child Behavior Checklist. AB - The Child Behavior Checklist's (CBCL) is often used as a screening instrument at first contact in standard child and adolescent psychiatric settings adding valuable information to the diagnostic process. However, its correspondence to clinical, in particular anxiety, diagnoses has not always been clear. Using parent reports from 2763 outpatients and 888 inpatients referred for psychiatric services, CBCL-anxiety scales were examined regarding their predictive validity and potential use as screening devices for anxiety disorders. Symptom scores across four diagnostic groups (anxiety disorder, emotional disorder, other psychiatric disorder and no psychiatric disorder) were calculated and compared; in addition ROC-analyses for the anxiety-disordered group were performed. Support for the validity of the "Anxiety Problems" scale (Achenbach et al., 2003) was found. However, AUC-values were only in the medium range (.71-.72) with substantial misclassification numbers proposing a limited utility of the scale as a screening instrument in our samples. Adding valuable information to the diagnostic process, the CBCL's associations with clinical anxiety diagnoses seem only moderate suggesting the additional use of other anxiety-specific instruments in clinical routine. PMID- 20362415 TI - Non sustained ventricular tachycardia in hypertrophic cardiomyopathy and new ultrasonic derived parameters. AB - BACKGROUND: The mechanism of sudden death in hypertrophic cardiomyopathy (HCM) is ventricular tachyarrhythmia emanating from myocyte disarray, fibrosis, and inhomogeneity in intramyocardial activation. Tissue synchronization imaging (TSI) allows the measurement of regional delay, while two-dimensional strain can be used to identify myocardial fibrosis. The aim of this study was to assess the relationship between new ultrasonically derived parameters and nonsustained ventricular tachycardia (NSVT) in patients with HCM. METHODS: Ninety-three patients with HCM (mean age, 36 +/- 16 years) and 30 patients with hypertension with secondary left ventricular (LV) hypertrophy (mean age, 42 +/- 10 years; 65% men) were studied. All underwent standard echocardiographic, TSI, and two dimensional strain examinations. Patients were followed every 3 months for 2 years. Holter monitoring was performed every 3 months. The primary endpoint was the occurrence of NSVT. RESULTS: Twenty-four patients (26%) had >or=1 episode of NSVT. Patients with NSVT had a higher value of maximal LV thickness (22 +/- 6 vs 19 +/- 5 mm, P = .04). There were no significant associations between NSVT on Holter monitoring and LV outflow gradient, New York Heart Association class, syncope, and medical therapy. N-terminal pro-brain natriuretic peptide values were significantly (P = .01) higher in patients with NSTV (1034 +/- 1088 vs 561 +/- 593 pg/mL). Patients with HCM and NSVT had (1) similar values on TSI-studied parameters to patients without NSVT, (2) significant reductions in basal and mid septal strain and in basal anterior-septal strain, and (3) more frequently peak systolic strain >or= -10% (P < .0001). In multivariate analysis, the presence of >3 LV segments with longitudinal two-dimensional strain >or= -10% (sensitivity, 81%; specificity, 97.1%; area under the curve, 0.944; P < .0001) was an independent predictor of NSVT. CONCLUSIONS: Using a simple, inexpensive, easily available, and bedside-usable tool, it was possible to recognize with good sensitivity and specificity patients with HCM at higher risk for NSVT. PMID- 20362416 TI - Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia. AB - Interictal high-frequency oscillations (HFO) were recently identified in recordings from depth macroelectrodes in epileptic patients. StereoEEG (SEEG) recordings were analyzed in four patients with medically intractable partial seizures due to focal cortical dysplasia type IIA. Characteristics of HFO within seizure onset zone (SOZ), irritative zone, and remote brain areas were investigated. Whilst the rate of occurrence for ripples (80-200 Hz) was significantly higher in recordings from within than outside the SOZ, the rate of fast ripples (200-450 Hz) was less reliable index of SOZ. Interestingly, the mean powers across subjects were significantly higher within than outside the SOZ in both ripple and fast ripple frequency ranges. Our study demonstrates a capacity of interictal HFO to detect the SOZ in focal cortical dysplasias. PMID- 20362417 TI - Diminished visual motion priming in schizophrenia. PMID- 20362419 TI - Fructose-1,6-bisphosphate aldolase A is involved in HaCaT cell migration by inducing lamellipodia formation. AB - BACKGROUND: No previous report has investigated the involvement of glycolytic enzymes in keratinocyte migration. Fructose-1,6-bisphosphate aldolase A (ALDOA) is a glycolytic enzyme bound to the cytoskeleton by certain growth factors, which are known to enhance keratinocyte migration. We postulated that ALDOA is involved in keratinocyte migration. OBJECTIVE: To investigate the possible role of ALDOA in keratinocyte migration. METHODS: The localization of endogenous ALDOA and the actin cytoskeleton was observed by laser scanning confocal microscopy in HaCaT cells. The effects of ALDOA on lamellipodia formation and migration were evaluated using ALDOA siRNA-transfected cells. In addition, the involvement of epidermal growth factor (EGF) in ALDOA-induced events was investigated. RESULTS: Strong ALDOA expression was observed along the ruffling membrane and lamellipodia, and it was colocalized with the actin cytoskeleton in lamellipodia. In a scratch wound assay, the wound recovery area was significantly decreased on transfection with ALDOA siRNA. The rate of lamellipodia-forming cells also decreased. On stimulation with EGF, the wound recovery area and ALDOA and its mRNA levels increased. On the other hand, ALDOA siRNA transfection suppressed EGF enhanced migration. CONCLUSION: We concluded that ALDOA is involved in keratinocyte migration following the induction of lamellipodia formation, and ALDOA-related migration is enhanced by EGF. PMID- 20362418 TI - Factors in sensory processing of prosody in schizotypal personality disorder: an fMRI experiment. AB - INTRODUCTION: Persons diagnosed with schizophrenia demonstrate deficits in prosody recognition. To examine prosody along the schizophrenia spectrum, antipsychotic-naive schizotypal personality disorder (SPD) subjects and healthy control subjects were compared. It was hypothesized that SPD subjects would perform more poorly; with cognitive and demographic factors contributing to the poor performance. The superior temporal gyrus (STG) was selected as the region-of interest (ROI) given its known abnormalities in SPD and its important role in the processing of prosody. METHODS: SPD and healthy comparison (HC) subjects were matched on age, IQ, and parental social-economic status (PSES). Cognitive measures included the Speech Sound Perception Test (SSPT) to examine phonological processing (SPD=68, HC=74) and the Verbal Fluency task to examine executive functioning (SPD=129, HC=138). The main experiment was a novel fMRI task of prosody identification using semantically neutral sentences spoken with emotional prosody (SPD=16, HC=13). Finally, volumetric measurement of the superior temporal sulcus (STS), a key region for processing prosody, and partially overlapping with the STG, was performed (SPD=30, HC=30). RESULTS: Phonological processing and executive functioning were both impaired in SPD subjects compared with HC subjects. Contrary to the prediction, SPD subjects, as a group, were similar to HC subjects in terms of correctly indentifying the emotion conveyed and reaction time. Within the SPD group, prosody identification accuracy was influenced by executive functioning, IQ and perhaps PSES, relationships not found with HC subjects. Phonological perception aided prosody identification in both diagnostic groups. As expected, both groups activated the STG while performing the prosody identification task. However, SPD subjects may have been less "efficient" in their recruitment of STG neurons. Finally, SPD subjects demonstrated a trend toward smaller STS volumes on the left, particularly the lower bank. CONCLUSIONS: These data suggest that subtle differences between SPD and controls in phonological processing, executive functioning, IQ, and possibly PSES, contributed to difficulty in processing prosody for some SPD subjects. PMID- 20362420 TI - Hydroxyapatite surface solubility and effect on cell adhesion. AB - In living organisms the biological hydroxyapatite is in constant contact with body fluids, such as blood serum and saliva. Thus, dissolution, solubility and precipitation take place as part of the interaction of this material with biological fluids in tissues. In this work we have obtained the solubility constant for the system formed from aqueous solutions in equilibrium with hydroxyapatite and thus indirectly obtained the composition of the modified hydroxyapatite surface. In order to check the effects of this equilibrium and of the modification that the surface of hydroxyapatite suffers in aqueous solutions, we cultured pre-osteoblasts onto hydroxyapatite discs before and after equilibrium. The results revealed key steps of the mechanism for the bioactivity of hydroxyapatite, which are the solubilization of hydroxyapatite and the equilibrium that is formed on the surface. These processes modify the hydroxyapatite surface, whose composition is changed to a new calcium phosphate compound with the chemical formula of CaHPO4. A clear description of the transformations that occur on the surface of hydroxyapatite and of the interplay between these transformations and cell activity are two fundamental aspects of processes in which hydroxyapatite takes part, such as bone substitution, bone remodeling, osteoporosis and caries. PMID- 20362421 TI - [Treatment of childhood dystonia]. AB - Dystonia is not uncommon in childhood, but is clinically very heterogeneous. Therefore, introduction and follow-up of the treatment of dystonia in children are often a challenge for the physicians. Progresses in functional neurosurgery have open new fields in the treatment of dystonia in children, but it should be managed by a multidisciplinary team. This paper reviews the various therapeutic options available for childhood-onset dystonia, with a specific attention to dosage and side effects of the drugs regarding pediatric population according to the data of the literature. The rational strategy for therapeutic management of the various types of childhood dystonia is discussed. PMID- 20362422 TI - Inhibition of tumor cell proliferation and induction of apoptosis in human lung carcinoma 95-D cells by a new sesquiterpene from hairy root cultures of Artemisia annua. AB - Artemisia annua is a rich source of many bioactive substances, and in our recent work, a new sesquiterpene, (Z)-7-acetoxy-methyl-11-methyl-3-methylene-dodeca 1,6,10-triene (AMDT), was isolated and identified from hairy roots culture of A. annua, and its bioactivity was characterized in this work. AMDT showed moderate cytotoxic activities against the human tumor cell lines of HO8910 (ovary), 95-D (lung), QGY (liver) and HeLa (cervix) by MTT assay, whose IC(50) values were ranged within 52.44-73.3 microM. As lung cancer is the No. 1 killer of global cancer patients, our interest is to investigate the ability of AMDT in inducing apoptosis of 95-D tumor cells. The 95-D cell growth was inhibited by AMDT, and the flow cytometry analysis showed its cell cycle was arrested in the G1 phase. The apoptotic rate of the cells increased in a dose-dependent manner. AMDT lowered the mitochondrial membrane potential and increased the expression of caspase-9 and -3. These results revealed that AMDT could efficiently induce 95-D cell apoptosis through mitochondrial dependent pathway, and it may be a potential chemotherapeutic agent. PMID- 20362423 TI - Experience of the Irish National Centre for hereditary haemorrhagic telangiectasia 2003-2008. AB - Hereditary haemorrhagic telangiectasia (HHT) is a group of autosomal dominant disorders of vascular structure. The Irish National Centre for HHT at the Mercy University Hospital, Cork, Ireland was founded in 2003. From 2003 to 2008, screening of 164 patients with contrast echocardiography, thoracic computerised tomography (CT) and cerebral magnetic resonance imaging (MRI) has identified 88 patients with definite HHT, 72 (82%) of whom had epistaxis, 70 (80%) had telangiectasia and 81 (92%) had a first-degree relative with HHT. We sought to describe the manifestations of HHT in an Irish population and to determine differences between internationally reported data. The HHT patient database was analysed to describe demographics, clinical manifestations and interventional procedures performed in all referred patients. Contrast echocardiography and/or CT were performed in 86 patients with definite HHT, identifying 27 patients (31%) with pulmonary arteriovenous malformations (pAVMs). Nineteen patients with single or multiple pAVMs had 28 embolisation procedures performed, with 1-6 pAVMs embolised per procedure. Cerebral MRI was performed in 78 (89%) patients and 2 (2.3%) had cerebral arteriovenous malformations (cAVMs). HHT prevalence is thought to be 1 in 2500-8000, suggesting that there are many undiagnosed cases in Irish patients. Internationally published data suggest a prevalence of 15-35% for pAVMs and 10-23% for cAVMs in patients with HHT. While the prevalence of pAVMs in our group is consistent with these data, the prevalence of cAVMs is considerably lower, suggesting that Irish patients with HHT may differ genotypically and phenotypically from those in other countries. PMID- 20362424 TI - Early detection of amyloid aggregation using intrinsic fluorescence. AB - Beta-amyloid (Abeta) aggregation, believed to be responsible for Alzheimer's disease, is monitored using its intrinsic fluorescence decay. Alterations in the fluorescence decay of tyrosine correlate with the Abeta aggregation at a much earlier stage than the traditionally used fluorescence intensity of Thioflavin T (ThT). Potentially the finding may underpin progress towards an earlier diagnosis of the onset of Alzheimer's disease and an improved approach to developing intervention therapies. PMID- 20362425 TI - Brachypodium distachyon genomics for sustainable food and fuel production. AB - Grass crops are the most important sources of human nutrition, and their improvement is centrally important for meeting the challenges of sustainable agriculture, for feeding the world's population and for developing renewable supplies of fuel and industrial products. We describe the complete sequence of the compact genome of Brachypodium distachyon (Brachypodium) the first pooid grass to be sequenced. We demonstrate the many favorable characteristics of Brachypodium as an experimental system and show how it can be used to navigate the large and complex genomes of closely related grasses. The functional genomics and other experimental resources that are being developed will provide a key resource for improving food and forage crops, in particular wheat, barley and forage grasses, and for establishing new grass crops for sustainable energy production. PMID- 20362426 TI - RNA traffic control of chromatin complexes. AB - It is widely accepted that the genome is regulated by histone modifications that induce epigenetic changes on the genome. However, it is still not understood how ubiquitously expressed chromatin modifying complexes are 'guided' to specific genomic sites to induce intricate patterns of epigenetic modifications. Previously believed to represent 'genome junk', it is now becoming increasingly clear that large non-coding RNAs associate with chromatin modifying complexes. Here we explore an intriguing hypothesis that large non-coding RNA molecules might represent a molecular trafficking system that modulates chromatin modifying complexes to establish specific epigenetic landscapes. PMID- 20362427 TI - Discrete capacity limits in visual working memory. AB - The amount of information we can actively maintain 'in mind' is very limited. This capacity limitation, known as working memory (WM) capacity, has been of great interest because of its wide scope influence on the variety of intellectual abilities. Recently, there has been an ongoing debate about how this capacity should be best characterized. One viewpoint argues that WM capacity is allocated in a discrete fashion with an upper limit of three to four representations. An alternative viewpoint argues that the capacity can be allocated in a continuous fashion with no upper limit in the number of representations. In this article, we will review recent neurobiological and behavioral evidence that has helped shape the debate regarding one of the more central mechanisms in cognitive neuroscience. PMID- 20362428 TI - Unraveling the auditory system of Drosophila. AB - Acoustic communication in flies is based on the production and perception of courtship song. Drosophila males sing to females during the courtship ritual, while females listen for the correct species-specific song parameters before deciding to mate. While we know that song is important for mating, the neural mechanisms involved in song recognition remain mysterious. However, the last few years have seen major advances in our understanding of the auditory system of Drosophila, including delineation of the neurons involved in song production, detailed characterization of the auditory receptor organ, and mapping of auditory projections into the brain. The stage is being set to tackle the auditory system of Drosophila in much the same way as has been done for its olfactory system. This review covers recent work and discusses prospects for future research on Drosophila audition. PMID- 20362429 TI - Translational research on u-PAR. AB - The urokinase receptor (u-PAR) is one of the most critical molecules in migration, invasion, intravasation, and metastasis and is also a key regulator between tumour cell proliferation and dormancy. It is overexpressed in most human solid cancer types, which has led to increasing translational and clinical research on this molecule. The current review discusses in particular the in vivo, translational, and putative clinical relevance of u-PAR in the context of this latest development. It outlines how u-PAR is already being used and might increasingly be applied as a diagnostic tool, for example, in distinguishing benign from malignant neoplasms, as a molecular marker for predicting clinical response to chemotherapy or novel targeted therapy, and finally as a promising tool for the development of novel cancer therapeutics. PMID- 20362430 TI - Adsorption of Pb(II) on activated carbon prepared from Polygonum orientale Linn.: kinetics, isotherms, pH, and ionic strength studies. AB - Low-cost activated carbon was prepared from Polygonum orientale Linn. (PL) by phosphoric acid activation. Its ability to adsorb Pb(II) ions from aqueous solutions was examined. Through SEM, XRD, BET, and FTIR analyses, the PL activated carbon (PLAC) was found to have a porous structure with a surface area of about 1400 m(2)/g. Carboxyl groups played an important role in the adsorption of Pb(II) through blocking studies. The sorption system followed a pseudo second order kinetic model, and the equilibrium time was obtained after 30 min. The adsorption isotherms were simulated well by the Langmuir model. The adsorption of Pb(II) on PLAC was strongly dependent on pH and ionic strength, indicating an ion exchange mechanism. Regeneration studies showed that PLAC could be used several times by desorption with an HCl reagent. PMID- 20362431 TI - Comparative study of thermochemical processes for hydrogen production from biomass fuels. AB - Different thermochemical configurations (gasification, combustion, electrolysis and syngas separation) are studied for producing hydrogen from biomass fuels. The aim is to provide data for the production unit and the following optimization of the "hydrogen chain" (from energy source selection to hydrogen utilization) in the frame of the Italian project "Filiera Idrogeno". The project focuses on a regional scale (Tuscany, Italy), renewable energies and automotive hydrogen. Decentred and small production plants are required to solve the logistic problems of biomass supply and meet the limited hydrogen infrastructures. Different options (gasification with air, oxygen or steam/oxygen mixtures, combustion, electrolysis) and conditions (varying the ratios of biomass and gas input) are studied by developing process models with uniform hypothesis to compare the results. Results obtained in this work concern the operating parameters, process efficiencies, material and energetic needs and are fundamental to optimize the entire hydrogen chain. PMID- 20362432 TI - Identification of activity related amino acid mutations of a GH9 termite cellulase. AB - Site-directed mutagenesis of the endo-beta-1,4-glucanase (EG) gene from the termite Reticulitermes speratus EG (RsEG) was performed to gain a better understanding of the role of certain amino acid residues in the activity of the enzyme. Three mutants, G91A, Y97W and K429A had higher activities towards carboxymethyl cellulose than the wild type. The mutations had synergistic effects since each single mutant exhibited about 3-4-fold of wild type activity, but the corresponding activities for double and triple mutants were 7-13-fold. Mutant G147R lost the enzymatic activity completely, suggesting G147 plays a significant role in maintaining enzyme activity. The predicted roles of Asp53, Asp56 and Glu411 in enzymatic catalysis were experimentally verified since the resultant mutants lost the enzyme activities. This study presents the first report on the relationship between amino acid residues and enzyme activity of termite EG, and the information will potentially be useful for industrial application of termite origin cellulase. PMID- 20362433 TI - Cellulose and cellodextrin utilization by the cellulolytic bacterium Cytophaga hutchisonii. AB - Cytophaga hutchinsonii is an abundant aerobic cellulolytic soil bacterium utilizing very few substrates as sole carbon and energy sources. In this study, growth of C. hutchinsonii on different substrates including crystalline cellulose, regenerated amorphous cellulose (RAC) as well as soluble sugars including cellodextrins was analyzed. Soluble sugars including glucose and cellodextrins were produced extracellularly when C. hutchinsonii was cultured on cellulose. Preferential use of cellulooligosaccharides as the carbon source by C. hutchinsonii was largely dependent on its inoculation status. Compared with glucose-grown cells, inoculation of cellobiose-grown cells led to a rapid assimilation of cellobiose or cellodextrins with longer-chain cellodextrins being hydrolyzed extracellularly to smaller oligomers during the culture. Further analysis of the distribution of cellulase activity revealed that, while the carboxymethylcellulase activity significantly induced by crystalline cellulose was highest in the outer membrane, the cellobiase activity was highest in the cytoplasmic membrane. These results suggest that membrane-bound cellulases may play an important role in cellulose solubilization by C. hutchinsonii and that metabolism of cello-oligosaccharides is a tightly coupled step in this process. PMID- 20362434 TI - Influence of nutritive factors on C50 carotenoids production by Haloferax mediterranei ATCC 33500 with two-stage cultivation. AB - The production of pigments by Haloferax mediterranei ATCC 33500 with two-stage cultivation in response to nutritive factors in culture media was studied. Sodium chloride and magnesium sulfate in the second-stage media showed a marked effect upon the production of pigments, and sodium acetate could enhance the production. As the cells were harvested at mid-log phase of growth in first-stage cultivation and transferred to the defined media containing 5% sodium chloride, 0.1% sodium acetate and 8% magnesium sulfate at 37 degrees C, 120 rpm for further 24 h of cultivation, H. mediterranei exhibited to be an efficient producer of pigments. The yield of pigments could reach up to 0.604 A(494 nm) mL(-1) broth. TLC analysis and the UV-Vis spectra of individual spots thereof revealed that H. mediterranei produced three red pigments of C(50) carotenoid, namely bisanhydrobacterioruberin, monoanhydrobacterioruberin and bacterioruberin, as well as a C(45) carotenoid, 2-isopentenyl-3,4-dehydrorhodopin. PMID- 20362435 TI - Kinetics of mesophilic anaerobic digestion of the organic fraction of municipal solid waste: Influence of initial total solid concentration. AB - The anaerobic mesophilic degradation of municipal waste has been studied in discontinuous lab-reactors with two different initial concentrations of OFMSW: R20, with 931.1mg DOC/L (20% TS), and R30, with 1423.4 mg DOC/L (30% TS). The anaerobic digestion process was favoured when it was carried on material with a total solids content of 20% in comparison to a similar process with 30% TS. A higher level of organic matter, in terms of DOC and VFA, 18.18% and 8.09% respect, was removed in the system with the lower amount of solids. The kinetics parameters showed higher active biomass and a higher coefficient for the production of methane at the lower loading. The highest maximum specific growth rate for the microorganisms (mu(MAX)) in the reactors with 20% TS, a value of 0.192 d(-1), was achieved in comparison to 0.131 d(-1) in the reactors with 30% TS. The inverse of the F:M ratio was higher in the R20 system with a value of 0.0104 (cf. 0.0006 in R30) and, as a result, the R30 system required longer hydrolytic and acidogenic stages. X(V0)/Y(X/S) and the yield coefficient for product generation (alpha(P/S)) were higher, by around 53%, for the R20 digester. PMID- 20362436 TI - Investigation of the metabolic inhibition observed in solid-substrate cultivation of Clostridium thermocellum on cellulose. AB - Metabolic inhibition of Clostridium thermocellum, when grown in a high solids environment, was investigated by comparing submerged fermentation (SmF), solid substrate cultivation (SSC) and solid-substrate cultivation with media replacement by periodic flushing (FSSC). Cellulose conversion extent and end product concentrations were measured over time. SmF converted approximately 65% of the cellulose in 240 h (10 days), whereas SSC converted <8% in the same period. FSSC converted approximately 25% and 47% of initial substrate after 240 h; 45% and 71% of initial substrate after 25 days, with media replacement every 24 and 12h, respectively. The SSC experienced higher initial production rates for all fermentation products, but could not sustain production rates. When acetate concentrations reached a critical point, the acetate decreased the intracellular volume of C. thermocellum cell suspensions at pH values similar to those observed in SSC. Acids produced by fermentation exacerbated the already unfavorable osmotic condition of SSC, resulting in metabolic inhibition. Consistent with this finding, approximately constant amounts of ethanol, acetate and lactate were produced during each flush of the FSSC. Flushed solid-substrate cultivation maintained favorable growth conditions for C. thermocellum even up to 25 days, allowing more total product to be formed than in the other cultivation methods. PMID- 20362437 TI - A facile method for improving the covalent crosslinking adsorption process of catalase immobilization. AB - In this paper, we introduced a polydiol (mixture of 1,2-propanediol, 1,3 propanediol, and 2,3-butanediol) to improve the covalent crosslinking adsorption process of immobilized catalase onto chitosan beads. The adsorption behavior was investigated by means of adsorption kinetics and adsorption isotherm. The protein content in crosslinking agent required for approximately 45 min to reach the relative equilibrium, and the protein content in solution of the control group and the pretreated group were 6.63 microg/mL and 6.20 microg/mL, respectively. The maximum catalase adsorption capacity of the control group and the pretreated group were observed as 23.118 microg/g and 25.688 microg/g at pH 7.0, respectively. Temperature profiles showed that 40 degrees C was the ideal temperature for active domain of catalase, and the relative activity of pretreated group was 1.12 times higher than that of the control group. The K(m) value of the control group (67 mM) was higher than that of the pretreated group (54 mM). Thermal stability, operational stability, and the effect of surfactant on catalase adsorption were also explored in this study. PMID- 20362438 TI - Comparison of atmospheric pressure effects on the anaerobic digestion of municipal solid waste. AB - This study compared the performance of anaerobic digestion (AD) of municipal solid waste under 101 kPa (R system) and 65.8 kPa (RPC system) - the atmospheric pressure on the Qinghai-Tibetan Plateau, China. Gas production, gas composition, degradation of volatile solids, pH, alkalinity, volatile fatty acids, and ammonia concentration were analyzed to examine how the two systems responded to change in the organic loading rate. The RPC system had a stronger buffering capacity and lower gas production rate and could achieve a higher loading rate. The pH in RPC recovered more rapidly in the starting stage and remained higher than that in R during the whole experiment, with an average difference of 0.2. During days 38 55, 56-70, and 71-125, the average methane production rates were 380.16, 318.67, and 402.21 L kg(-1) VS in R and 367.40, 299.04, and 275.06 L kg(-1) VS in RPC, respectively. PMID- 20362439 TI - Organoarsenic resistance and bioremoval of Acidithiobacillus ferrooxidans. AB - The tolerance and bioremoval of dimethylarsinic acid (DMA(V)) by Acidithiobacillus ferrooxidans (A. ferrooxidans) were investigated here. The inhibitory concentration (IC) of DMA(V) was determined for A. ferrooxidans. The effects of various parameters such as pH, contact time, initial DMA(V) concentration, biosorbent dose and temperature were systematically examined to study the biosorption processes. Results indicated that Langmuir model fitted better than Freundlich model to the equilibrium data. Analysis of kinetic data showed that the biosorption processes of DMA(V) involved pseudo-second-order kinetics. Thermodynamic analysis showed that the biosorption of DMA(V) onto A. ferrooxidans was feasible, spontaneous, endothermic and chemisorptive under examined conditions. Fourier transform infrared spectroscopy (FTIR) showed the involvement of -OH, -NH and -SO(3) groups in the biosorption process. PMID- 20362440 TI - Utilization of wastewater originated from naturally fermented virgin coconut oil manufacturing process for bioextract production: physico-chemical and microbial evolution. AB - Production of virgin coconut oil via natural fermentation has led to large amount of wastes being generated, i.e., coconut pulp and wastewater containing coconut creme. Objective of this study is to gain more insight into the feasibility of utilization of such wastes as raw materials together with several types of wastes such as fish waste and/or pineapple peel for bioextract production. Chemical, physico-chemical and biological changes including phytotoxicity of the fermented mixture were closely monitored. Physical observation suggested that fermentation of bioextract obtained with fish waste appeared to be complete within the first month of fermentation while bioextract obtained using pineapple waste seemed to be complete after 8 months post-fermentation. Fermentation broth is of blackish color with alcoholic as well as acidic odour with no gas bubble and/or yeast film present on top of the surface. During the whole fermentation interval, several attributes of both bioextracts, e.g., pH, chemical oxygen demand (COD) and organic acids, were statistically different. Further, the total bacteria and lactic acid bacteria present in pineapple bioextract were statistically higher than those of the fish bioextract (p<0.01). The highest germination indices of 123 and 106 were obtained at 21 and 14 days post-fermentation for fish and pineapple bioextracts, respectively. In addition, qualities of both bioextracts conformed well with those specified by the Thai standard for liquid biofertilizer after 1 month fermentation. Results further showed that wastewater derived from virgin coconut oil manufacturing process could effectively be employed together with other types of wastes such as fish waste and pineapple peel for bioextract production. However, for the best bioextract quality, fermentation should be carefully planned since over fermentation led to bioextract of low qualities. PMID- 20362441 TI - The effect of environmental and process parameters on flocculation treatment of high dry matter swine manure with polymers. AB - This paper reports on the effects of environmental conditions and process parameters on flocculation of high dry matter (average DM of 7.3%) swine manure with cationic polymers with 10%, 35%, and 55% charge densities (CDs). Polymer solutions prepared with hard and distilled water allowed similar suspended solids (SS) reductions in the initial 24h. After 3-7 days at 20 degrees C, however, the efficiency of the hard water solutions started to decline, while the polymers made with distilled water maintained their performance for up to 10 days. The 10% CD polymer was considerably less affected than the 35% CD polymer by the age of the hard water solutions. During polymer injection, minimum velocity gradients (G) of 108 and 253 s(-1) were required to maximized efficiency of the 10% and 35% CD polymer, respectively. Flocculation mixing velocities up to 84 s(-1) and mixing times between 1 and 30 min had no effect on polymer efficiency. However, mixing at 22s(-1) for more than 30 min decreased SS reduction. Adding polymer in multiple injections did not improve the efficiency of medium and high CD polymers, and adversely affected that of the low CD polymer, maybe because of repeated rapid mixing cycles which ruptured the flocs. Polymer performance was not affected by operating temperature between 6 and 25 degrees C. These results were collected on a laboratory-scale apparatus and remain to be validated at larger scale. PMID- 20362442 TI - Cytotoxicity against KB and NCI-H187 cell lines of modified flavonoids from Kaempferia parviflora. AB - Flavones 1-4 isolated from Kaempferia parviflora were used for structural modification. Sixteen flavonoid derivatives, including four new derivatives, were synthesized and evaluated for cytotoxicity against KB and NCI-H187 cell lines. Flavanones 2a-4a demonstrated higher cytotoxic activity than the parent compounds. Cytotoxicity against KB cell line of oxime 1c was about 7 times higher than the ellipticine standard. Interestingly, oximes 1c and 2c exhibited highly potent cytotoxicity against NCI-H187 cell line with IC(50) values of 0.014 and 0.23 microM, respectively. Oximes 4c and 5c showed strong cytotoxicity against NCI-H187 cell line with IC(50) values of 4.04 and 2.32 microM, respectively. PMID- 20362443 TI - 2-C-methyluridine modified hammerhead ribozyme against the estrogen receptor. AB - A new synthesis of 2'-C-methyluridine phosphoramidite is presented. Special emphasis is dedicated to the improvement of the protection of the tertiary 2' hydroxyl group. Comparison to previous protecting strategies and analysis of stability under 5'-DMTr removing conditions are discussed. The synthetic incorporation of this modified nucleoside into the catalytic core of a hammerhead ribozyme against the estrogen receptor alpha protein (ER-alpha), and transfection experiments in MCF-7 cell line are also presented. PMID- 20362444 TI - Structure-based rational design, synthesis and antifungal activity of oxime containing azole derivatives. AB - In an attempt to find novel azole antifungal agents with improved activity and broader spectrum, computer modeling was used to design a series of new azoles with piperidin-4-one O-substituted oxime side chains. Molecular docking studies revealed that they formed hydrophobic and hydrogen-bonding interactions with lanosterol 14alpha-demethylase of Candida albicans (CACYP51). In vitro antifungal assay indicates that most of the synthesized compounds showed good activity against tested fungal pathogens. In comparison with fluconazole, itraconazole and voriconazole, several compounds (such as 10c, 10e, and 10i) show more potent antifungal activity and broader spectrum, suggesting that they are promising leads for the development of novel antifungal agents. PMID- 20362446 TI - Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. AB - The Piwi-interacting RNAs (piRNAs) have been shown to safeguard the animal germline genome against deleterious retroelements [1-9]. Many factors involved in the production of piRNAs localize to nuage, a unique perinuclear structure in animal germline cells [10], suggesting that nuage may function as a site for processing of germline piRNAs [1, 3-6, 11-14]. Here we report a conserved yet uncharacterized component of the germline piRNA pathway, Tejas (Tej), which localizes to nuage. tej is required for the repression of some retroelements and for the production of sufficient germline piRNAs. The localization of Tej to nuage depends on vasa (vas) [15] and spindle-E (spn-E) [1, 16, 17] while it regulates the localization of Spn-E, Aubergine (Aub) [3, 4, 14], Argonaute3 (Ago3) [5], Krimper (Krimp) [13], and Maelstrom (Mael) [18] to nuage. Aub, Vas, and Spn-E physically interact with Tej through the N terminus containing the conserved tejas domain, which is necessary and sufficient for its germline function. Aub and Spn-E also bind to the tudor domain at the C terminus. Our data suggest that Tej contributes to the formation of a macromolecular complex at perinuclear region and engages it in the production of germline piRNAs. PMID- 20362445 TI - Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. AB - BACKGROUND: Altered expression of apicobasal polarity factors is associated with cancer in vertebrates and tissue overgrowth in invertebrates, yet the mechanisms by which these factors affect growth-regulatory pathways are not well defined. We have tested the basis of an overgrowth phenotype driven by the Drosophila protein Crumbs (Crb), which nucleates an apical membrane complex that functionally interacts with the Par6/Par3/aPKC and Scrib/Dlg/Lgl apicobasal polarity complexes. RESULTS: We find that Crb-driven growth is dependent upon the Salvador/Warts/Hippo (SWH) pathway and its transcriptional effector Yorkie (Yki). Expression of the Crb intracellular domain elevates Yki activity, and this correlates in tissues and cultured cells with loss of Expanded (Ex), an apically localized SWH component that inhibits Yki. Reciprocally, loss of crb elevates Ex levels, although this excess Ex does not concentrate to its normal location at apical junctions. The Ex-regulatory domain of Crb maps to the juxtamembrane FERM binding motif (JM), a cytoskeletal interaction domain distinct from the PDZ binding motif (PBM) through which Crb binds polarity factors. Expression of Crb JM drives Yki activity and organ growth with little effect on tissue architecture, while Crb-PBM reciprocally produces tissue architectural defects without significant effect on Yki activity. CONCLUSIONS: These studies identify Crb as a novel SWH regulator via JM-dependent effects on Ex levels and localization and suggest that discrete domains within Crb may allow it to integrate junctional polarity signals with a conserved growth pathway. PMID- 20362447 TI - Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. AB - BACKGROUND: The Drosophila neoplastic tumor suppressor Lethal (2) giant larvae (Lgl) controls apicobasal cell polarity and proliferation. We have previously shown that lgl(-) clones in the developing eye exhibit ectopic proliferation and suppress apoptosis without affecting apicobasal cell polarity. Ectopic expression of the apical polarity regulators atypical protein kinase C (aPKC) and Crumbs also leads to increased cell proliferation and/or survival. Here we investigate how these cell polarity regulators control proliferation and survival. RESULTS: We report that depletion of lgl in eye epithelial tissue, where polarity is maintained, results in upregulation of targets of the Salvador/Warts/Hippo (SWH) tumor suppressor pathway. Consistent with this, the SWH pathway transcriptional coactivator Yorkie is hyperactivated in Lgl-deficient tissue and is rate limiting for lgl(-) phenotypes. Overexpression of the apical polarity regulators Crumbs or aPKC also leads to ectopic expression of SWH pathway targets without affecting polarity. We show that Lgl depletion or aPKC overexpression results in comislocalization of Hippo and Ras-associated domain family protein (RASSF), consistent with RASSF's ability to block Hippo activation by Salvador. In contrast, Crumbs overexpression leads to mislocalization of Expanded away from the apical cortex, which is predicted to deregulate the pathway. CONCLUSIONS: Collectively, our data reveal that the cell polarity regulators Lgl, aPKC, and Crumbs regulate the SWH pathway by two distinct pathways: Lgl acts antagonistically to aPKC to regulate Hippo and RASSF localization, whereas Crumbs regulates Expanded localization. Thus, our study implicates Lgl, aPKC, and Crumbs as regulators of tissue growth via the SWH pathway. PMID- 20362448 TI - GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation. AB - Cell locomotion and endocytosis are powered by the rapid polymerization and turnover of branched actin filament networks nucleated by Arp2/3 complex. Although a large number of cellular factors have been identified that stimulate Arp2/3 complex-mediated actin nucleation, only a small number of studies so far have addressed which factors promote actin network debranching. Here, we investigated the function of a conserved homolog of ADF/cofilin, glia maturation factor (GMF). We found that S. cerevisiae GMF (also called Aim7) localizes in vivo to cortical actin patches and displays synthetic genetic interactions with ADF/cofilin. However, GMF lacks detectable actin binding or severing activity and instead binds tightly to Arp2/3 complex. Using in vitro evanescent wave microscopy, we demonstrated that GMF potently stimulates debranching of actin filaments produced by Arp2/3 complex. Further, GMF inhibits nucleation of new daughter filaments. Together, these data suggest that GMF binds Arp2/3 complex to both "prune" daughter filaments at the branch points and inhibit new actin assembly. These activities and its genetic interaction with ADF/cofilin support a role for GMF in promoting the remodeling and/or disassembly of branched networks. Therefore, ADF/cofilin and GMF, members of the same superfamily, appear to have evolved to interact with actin and actin-related proteins, respectively, and to make mechanistically distinct contributions to the remodeling of cortical actin structures. PMID- 20362449 TI - Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior. AB - The brain of Drosophila melanogaster contains approximately 150 circadian neurons [1] functionally divided into morning and evening cells that control peaks in daily behavioral activity at dawn and dusk, respectively [2, 3]. The PIGMENT DISPERSING-FACTOR (PDF)-positive small ventral lateral neurons (sLN(v)s) promote morning behavior, whereas the PDF-negative sLN(v) and the dorsal lateral neurons (LN(d)s) generate evening activity. Much less is known about the approximately 120 dorsal neurons (DN1, 2, and 3). Using a Clk-GAL4 driver that specifically targets a subset of DN1s, we generated mosaic per(0) flies with clock function restored only in these neurons. We found that the Clk4.1M-GAL4-positive DN1s promote only morning activity under standard (high light intensity) light/dark cycles. Surprisingly, however, these circadian neurons generate a robust evening peak of activity under a temperature cycle in constant darkness. Using different light intensities and ambient temperatures, we resolved this apparent paradox. The DN1 behavioral output is under both photic and thermal regulation. High light intensity suppresses DN1-generated evening activity. Low temperature inhibits morning behavior, but it promotes evening activity under high light intensity. Thus, the Clk4.1M-GAL4-positive DN1s, or the neurons they target, integrate light and temperature inputs to control locomotor rhythms. Our study therefore reveals a novel mechanism contributing to the plasticity of circadian behavior. PMID- 20362450 TI - A two-step inactivation mechanism of Myt1 ensures CDK1/cyclin B activation and meiosis I entry. AB - Activation of CDK1 is essential for M-phase entry both in mitosis and meiosis. G2 arrested oocytes contain a pool of CDK1/cyclin B complexes that are maintained inactive because of the phosphorylation of CDK1 on Thr14 and Tyr15 by the Wee1 family protein kinase Myt1, whose inhibition suffices to induce meiosis I entry [1-5]. CDK1/XRINGO and p90Rsk can both phosphorylate and downregulate Myt1 activity in vitro [6, 7]. Here we identify five p90Rsk phosphorylation sites on Myt1 that are different from the CDK1/XRINGO sites, and we show how both kinases synergize during oocyte maturation to inhibit Myt1, ensuring meiotic progression. We found that phosphorylation of Myt1 by CDK1/XRINGO early during oocyte maturation not only downregulates Myt1 kinase activity but also facilitates the recruitment of p90Rsk and further phosphorylation of Myt1. Mutation of the five p90Rsk residues to alanine impairs Myt1 hyperphosphorylation during oocyte maturation and makes Myt1 resistant to the inhibition by p90Rsk. Importantly, Myt1 phosphorylated by p90Rsk does not interact with CDK1/cyclin B, ensuring that the inhibitory phosphorylations of CDK1 cannot take place after meiosis I entry and contributing to the all-or-none meiotic response. PMID- 20362451 TI - Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe. AB - Electric signals surround tissues and cells and have been proposed to participate in directing cell polarity in processes such as development, wound healing, and host invasion [1, 2]. The application of exogenous electric fields (EFs) can direct cell polarization in cell types ranging from bacteria and fungi to neurons and neutrophils [3-7]. The mechanisms by which EFs modulate cell polarity, however, remain poorly understood. Here we introduce the fission yeast Schizosaccharomyces pombe as a model organism to elucidate the mechanisms underlying this process. In these rod-shaped cells, an exogenous EF reorients cell growth in a direction orthogonal to the field, producing cells with a bent morphology. A candidate genetic screen identifies conserved factors involved in this process: an integral membrane proton ATPase pma1p that regulates intracellular pH, the small GTPase cdc42p, and the formin for3p that assembles actin cables. Interestingly, mutants in these genes still respond to the EF but orient in a different direction, toward the anode. In addition, EFs also cause electrophoretic movement of cell wall synthase complex proteins toward the anode. These data suggest molecular models for how the EF reorients cell polarization by modulating intracellular pH and steering cell polarity factors in multiple directions. PMID- 20362453 TI - Does footwear type impact the number of steps required to reach gait steady state?: an innovative look at the impact of foot orthoses on gait initiation. AB - Many studies have attempted to better elucidate the effect of foot orthoses on gait dynamics. To our knowledge, most previous studies exclude the first few steps of gait and begin analysis at steady state walking. These unanalyzed steps of gait may contain important information about the dynamic and complex processes required to achieve equilibrium for a given gait velocity. The purpose of this study was to quantify gait initiation and determine how many steps were required to reach steady state walking under three footwear conditions: barefoot, habitual shoes, and habitual shoes with a prefabricated foot orthoses. Fifteen healthy subjects walked 50m at habitual speed in each condition. Wearing habitual shoes with the prefabricated orthoses enabled subjects to reach steady state walking in fewer steps (3.5 steps+/-2.0) compared to the barefoot condition (5.2 steps+/ 3.0; p=0.02) as well as compared to the habitual shoes condition (4.7 steps+/ 1.6; p=0.05). Interestingly, the subjects' dynamic medial-lateral balance was significantly improved (22%, p<0.05) by using foot orthoses compared to other footwear conditions. These findings suggest that foot orthoses may help individuals reach steady state more quickly and with a better dynamic balance in the medial-lateral direction, independent of foot type. The findings of this pilot study may open new avenues for objectively assessing the impact of prescription footwear on dynamic balance and spatio-temporal parameters of gait. Further work to better assess the impact of foot orthoses on gait initiation in patients suffering from gait and instability pathologies may be warranted. PMID- 20362452 TI - DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila. AB - BACKGROUND: Daily behaviors in animals are determined by the interplay between internal timing signals from circadian clocks and environmental stimuli such as light. How these signals are integrated to produce timely and adaptive behavior is unclear. The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity. RESULTS: Mutants of a novel ion channel, narrow abdomen (na), lack a robust increase in activity in response to light and show reduced anticipatory behavior and free-running rhythms, providing a genetic link between photic responses and circadian clock function. We used tissue-specific rescue of na to demonstrate a role for approximately 16-20 circadian pacemaker neurons, a subset of the posterior dorsal neurons 1 (DN1(p)s), in mediating the acute response to the onset of light as well as morning anticipatory behavior. Circadian pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) are especially important for morning anticipation and free-running rhythms and send projections to the DN1(p)s. We also demonstrate that DN1(p)Pdfr expression is sufficient to rescue, at least partially, Pdfr morning anticipation defects as well as defects in free-running rhythms, including those in DN1 molecular clocks. Additionally, these DN1 clocks in wild-type flies are more strongly reset to timing changes in PDF clocks than other pacemaker neurons, suggesting that they are direct targets. CONCLUSIONS: Taking these results together, we demonstrate that the DN1(p)s lie at the nexus of PDF and photic signaling to produce appropriate daily behavior. PMID- 20362454 TI - Nonproportionality of electron response using CCT: plastic scintillator. AB - The scintillation response of a plastic scintillator (NE102) has been characterized using compton coincidence technique. The coincidence technique allowed detection of nearly monoenergetic internal electrons resulting from the scattering of incident 662keV gamma-rays within a primary NE102 detector. Scattered gamma-rays were detected using a secondary NaI(Tl) detector in a coincidence mode. The electron response nonproportionality of NE102 plastic scintillator was measured using this technique for electron energies ranging from 28 to 436keV, by varying the scattering angle. The NE102 showed a good proportionality of light yield within 3% at energies between 90 and 436keV. Below 90keV, the light yield decreases by about 20% upon lowering the electron energy to 28keV. The electron energy resolution of NE102 was also measured using this technique in the energy range from 68 to 436keV. It has been found that the energy resolution varies from 25.2% at 68keV to 11.8% at 436keV. PMID- 20362455 TI - Surgical protocols and outcome for the treatment of maxillofacial fractures in children: 9 years' experience. AB - Trauma and facial fractures in a population of children have been analysed in several studies mainly regarding their incidence and much less their treatment modalities. AIM: The aim of this study was to retrospectively analyse the treatment methods and outcome of facial fractures in children and young adolescents during the last decade and to discuss findings and propose treatment protocols. PATIENTS AND METHODS: Patients of the Paediatric Maxillofacial department, treated for fractures of the facial skeleton were included in the study. Open reduction and osteosynthesis plate fixation (titanium and resorbable material) was the main treatment method with conservative treatment saved for selected cases. Titanium plates were removed after bone healing. Intermaxillary fixation (IMF) was not used regularly in mandibular fractures, with the exception of condylar fractures. RESULTS: 156 children and young adolescents with 208 fracture sites in total were treated. 139 fracture sites (66.8%) were treated with open reduction and 69 conservatively. The mandible was affected in 49.0% of the cases, the maxilla in 21.2% (both with the alveolar process fractures included), the zygomatic complex in 10.1%, the orbital walls in 9.6%. There were 38 alveolar process fractures. CONCLUSION: The results of the fracture treatment verified the usefulness of open reduction and plate fixation in children. There was no need for wire suspension and only occasional need for IMF. Closed reduction was selectively applied in condylar fractures and dento-alveolar trauma. PMID- 20362456 TI - Impact of untreated mild-to-moderate mitral regurgitation at the time of isolated aortic valve replacement on late adverse outcomes. AB - OBJECTIVE: The impact of untreated mild-to-moderate mitral regurgitation (MR) on patients undergoing isolated aortic valve replacement (AVR) is uncertain. The aim of this study is to investigate its long-term effects on outcomes. METHOD: We retrospectively reviewed 193 consecutive patients undergoing isolated AVR between 1993 and 2007. The mean age of the study group was 64+/-12 years, 59% were male and the mean preoperative ejection fraction was 59+/-12%. The pathologic aetiology and degree of MR was determined on preoperative echocardiogram. Patients were stratified into preoperative no/trivial MR (group I; n=134) versus mild-to-moderate MR (group II; n=59). The aetiology of MR in group II was either organic (n=35, 60%) or functional (n=24, 41%). Survival and functional outcome were compared between the two groups and analyses for predictors of adverse events were performed by the Cox proportional hazard model. RESULTS: Operative mortality was 2.6% (n=5). In group II, mean degree of MR significantly decreased from 2.1+/-0.3 to 1.6+/-0.8 during the late period (p=0.003). The improvement in MR grade was more obvious in patients with functional aetiology. Although the actuarial survival was not significantly different between groups, freedom from re-admission for heart failure at 10 years was significantly lower in group II than in group I (23% vs 83%; p=0.002). Multivariate analysis demonstrated that independent predictors of heart failure were presence of mild-to-moderate MR (p=0.012, odds ratio (OR) 3.8) and left ventricular ejection fraction (p=0.004, OR 0.95). CONCLUSION: Despite the significant reduction after isolated AVR, preoperative mild-to-moderate MR is an independent risk factor impacting long term functional outcome. Our results suggested that the concomitant mitral valve surgery for mild-to-moderate MR is warranted, especially in patients with reduced left ventricular function. PMID- 20362457 TI - Slower progression of atherosclerosis in vein grafts harvested with 'no touch' technique compared with conventional harvesting technique in coronary artery bypass grafting: an angiographic and intravascular ultrasound study. AB - OBJECTIVES: In a long-term randomised coronary artery bypass grafting (CABG) study, the patency rate using a new 'no touch' (NT) vein-graft preparation technique was superior to the conventional (C) technique. This cineangiographic and intravascular ultrasound (IVUS) substudy examined possible mechanisms. METHODS: A total of 45 patients (118 grafts) in the NT group and 46 patients (112 grafts) in the C group had patent grafts at short-term follow-up after 18 months. Thirty-seven patients (91 grafts) in the NT group and 37 patients (77 grafts) in the C group had patent grafts at long-term follow-up after 8.5 years, and were evaluated on a scale from 0 (normal) to 2 (significant stenosis) by cineangiogram. IVUS was performed in 15 NT grafts and 14 C grafts in the short term follow-up, and 27 NT grafts and 26 C grafts in the long-term follow-up, in grafts considered normal by the cineangiogram. The grafts were evaluated with respect to lumen volume, intimal thickness, incidence of plaque and plaque components. RESULTS: In the short-term follow-up, the cineangiogram showed more normal grafts (89.0% in the NT group compared with 75.0% in the C group), and the number of grafts with stenosis was 11.0% in the NT group compared with 25.0% in the C group (p=0.006). IVUS showed less mean intimal thickness (0.43 (0.07)mm vs 0.52 (0.08)mm; p=0.03), less grafts with considerable intimal hyperplasia (>= 0.9 mm; 20% vs 78.6%; p=0.011) and fewer patients with considerable hyperplasia (>= 0.9 mm; 25% vs 100%; p=0.007). In the long-term follow-up, the cineangiogram showed more normal grafts, with 91.2% in the NT group compared with 83.1% in the C group; there were fewer grafts with significant stenosis, with 7.7% in the NT group compared with 15.6% in the C group (p=0.14). IVUS showed fewer grafts containing multiple plaques (14.8% vs 50%; p=0.008), less advanced plaque with lipid (11.8% vs 63.9%; p=0.0004) and less maximal plaque thickness (1.04 (0.23)mm vs 1.32 (0.25)mm; p=0.02) in the NT group compared with the C group. CONCLUSION: The superior long-term patency rate using the NT vein-graft technique at CABG could be explained by a significantly slower progression of atherosclerosis. PMID- 20362458 TI - Unusual insertion of a mitral chord causing severe valve regurgitation. PMID- 20362459 TI - Advantages of preoperative three-dimensional contrast-enhanced computed tomography for anomalous pulmonary artery in video-assisted thoracoscopic segmentectomy. PMID- 20362460 TI - Where is the ruptured bronchial artery aneurysm? PMID- 20362461 TI - Lipocalin-2 controls the expression of SDF-1 and the number of responsive cells in bone. AB - Lipocalin-2 (LCN2) is a member of the lipocalin family, small secreted proteins functioning as modulators of many different physiological processes including cell differentiation, proliferation and apoptosis. LCN2 expression is also up regulated in several pathological conditions, including inflammation and cancer. LCN2 synthesis has been described in epithelia, bone and cells of the immune system. Despite its wide expression the role of LCN2 remains to be fully elucidated. To better understand the role of this lipocalin in the bone/bone marrow system we generated transgenic mice over-expressing LCN2 specifically in bone under the control of a type I collagen promoter. In the bone marrow of these transgenic mice we observed an increased expression of SDF-1 that correlated with an increased number of CD34+/CXCR4+ (SDF-1 receptor) cells. To some extent, this appeared due to an enhanced cell proliferation rate. The higher level of the factor synthesis and the increased number of cells expressing its receptor was maintained during animal aging. Our results show that LCN2 could play a role in determining the number of CD34+/CXCR4+ precursor cells in the bone marrow thus contributing to the control of the bone marrow microenvironment. PMID- 20362462 TI - The protein equivalent of nitrogen appearance in critically ill acute renal failure patients undergoing continuous renal replacement therapy. PMID- 20362463 TI - Lanthanum carbonate is an effective hypophosphatemic agent for hemodialysis patients intolerant of other phosphate binders. AB - BACKGROUND: Lanthanum carbonate (LC) is a noncalcium-containing phosphate binder of proven utility in treating hyperphosphatemia in dialysis patients, and displays a good tolerability profile. OBJECTIVE: This study addressed whether this tolerability profile could result in improved phosphate control in patients intolerant of other phosphate binders, and who remain hyperphosphatemic despite intensive dietary advice and adequate dialysis provision. DESIGN, SETTING, AND PATIENTS: This 18-month study, from a large urban hemodialysis unit, studied 55 patients identified by the multidisciplinary team as fulfilling the following criteria: persistent hyperphosphatemia; intolerance of, or admitted nonadherence to, prescribed phosphate binders (either calcium-based or sevelamer); and provision of adequate dialysis (urea reduction ratio, >65%). INTERVENTION AND MAIN OUTCOME MEASURE: LC was substituted for existing phosphate binders, and results were compared between baseline and 3 months after the initiation of LC. RESULTS: A significant fall in phosphate level from 2.28+/-0.55mmol/L to 1.89+/ 0.45mmol/L (7.06+/-1.70mg/dL to 5.85+/-1.39mg/dL) was evident 3 months after the medication switch (P < .001). This fall was associated with a significant increase in the number of patients achieving United Kingdom Renal Association guidelines for serum phosphate level (17% to 48%; P=.001). Mean phosphate-binder pill burden fell significantly by 3 months after the initiation of LC, from 7.8+/ 3.4 tablets daily to 3.6+/-2.3 tablets daily. A small but significant increase also occurred in serum bicarbonate levels, from 23.3+/-2.2mmol/L (23.3+/-2.2 mEq/L) at baseline to 23.9+/-2.5mmol/L (23.9+/-2.5 mEq/L) at 3 months (P=.03). This was observed despite a prescribed reduction in dialysate bicarbonate concentration across the population (P=.03). CONCLUSION: This study demonstrated the utility of LC in hemodialysis patients intolerant of alternative phosphate binders, and suggests an advantage of this agent in this patient group. PMID- 20362464 TI - Silver for the Society for Cardiovascular Pathology-SCVP Turns 25. PMID- 20362466 TI - Vagus nerve stimulation: outcome and predictors of seizure freedom in long-term follow-up. AB - OBJECTIVES: To present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS). METHODS: All patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6-9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years. RESULT: Ten patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P=0.014, HR=0.112 (95% CIs, 0.019 0.642), cortical dysgenesis P=0.007, HR=0.065 (95% CIs, 0.009-0.481) and younger age at implantation P=0.026, HR=7.533 (95% CIs 1.28-44.50) were independent predictors of seizure freedom in the long-term follow-up. CONCLUSION: VNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS. PMID- 20362467 TI - Comparison of pullout strength between 3.5-mm fully threaded, bicortical screws and 4.0-mm partially threaded, cancellous screws in the fixation of medial malleolar fractures. AB - Displaced medial malleolus fractures are considered unstable and typically require open reduction and internal fixation for anatomic reduction and early joint range of motion. These fractures are usually fixated with either compression lag screws or tension band wiring depending on the fracture pattern, size of the distal fragment, and bone quality. When fracture fixation fails, it is typically in pullout strength. Failure of primary bone healing can result in nonunion, malunion, and need for revision surgery. The current study wished to explore a potentially stronger fixation technique in regard to pullout strength for medial malleolar fractures compared with traditional cancellous screws. This was a comparative study of the relative pullout strength of 2 fully threaded 3.5 mm bicortical screws versus 2 partially threaded 4.0-mm cancellous screws for the fixation of medial malleolar fractures. Ten fresh-frozen limbs from 5 cadavers, mean age 79 years (range of 65-97 years), were tested using the Instron 8500 Plus system. The median force recorded at 2 mm of distraction using unicortical partially threaded cancellous screws was 116.2 N (range 70.2 to 355.5N) compared with 327.6 N (range 117.5 to 804.3 N) in the fully threaded bicortical screw (P = .04). The unicortical screw fixation displayed only 64.53% of the median strength noted with the bicortical screw fixation at clinical failure. The current study demonstrated statistically significantly greater pullout strength for 3.5-mm bicortical screws when compared with 4.0-mm partially threaded cancellous screws used to fixate medial malleolar fractures in a cadaveric model. PMID- 20362468 TI - Subcutaneous polypoid lipoma of the first intermetatarsal space mimicking rudimentary polydactyly. AB - A case of a subcutaneous polypoid lipoma, presenting as a rudimentary polydactyly, is reported. The lesion was located between the first and second digits and extended into the first intermetatarsal space in a polypoid fashion. Radiographically, there were no osseous structures associated with the mass, and preliminary biopsy results showed no evidence of malignancy. The patient was treated with marginal excision of the mass and reduction of the intermetatarsal space with a Mini TightRope (Arthrex, Inc., Naples, FL). The final pathological diagnosis was polypoid lipomas, and the patient experienced a full and uneventful recovery. PMID- 20362469 TI - Letter to the editor. PMID- 20362471 TI - Reconstruction of achilles tendon rupture with combined V-Y plasty and gastrocnemius-soleus fascia turndown graft. AB - A reconstructive technique for treatment of Achilles tendon rupture with an extensive defect is presented. The primary goal of this salvage procedure is to create functional length and anatomic continuity among muscle, tendon, and bone. The procedure uses a combination of fascial advancement techniques: the V-Y advancement and the gastrocnemius-soleus fascia turndown graft. In this technique, the inverted "V" inscribed on the proximal gastrocnemius fascia is partially elevated from the underlying soleus and twisted 180 degrees on itself to augment the repair. Advancing the musculotendinous junction and creating a turndown graft provide substantial length. This combined technique allows the surgeon to repair ruptures with segmental defects greater than 10 cm in length. PMID- 20362472 TI - Effectiveness of instituting a specific bed protocol in reducing complications associated with bed rest. AB - Pressure ulceration, deep venous thromboembolism, and hospital-acquired pneumonia are well-known complications of bed rest. This retrospective, single-center, observational cohort study evaluated the effectiveness of instituting bed rest protocol that included specific positioning, continuous heel off-loading, recumbent upper and lower body bed exercises, scheduled incentive spirometry, frequent position changes, and thromboprophylaxis (chemical, mechanical, or both), in reducing the incidence of pressure ulceration, deep venous thromboembolism, and hospital-acquired pneumonia in consecutive patients admitted for at least 7 days. A total of 29 patients (24 males, 5 females) were included in this study, with a mean age of 62.5 (median 63, range 17 to 84) years. The mean length of bed rest was 13.1 (median 10, range 7 to 31) days; and, the mean length of hospital stay was 21.1 (median 17, range 8 to 72) days. During hospitalization, 2 (6.9%) patients developed one or more of the complications measured, with 1 developing a posterior heel pressure ulcer that resolved with local care and another who developed deep venous thrombosis without pulmonary embolism, managed with therapeutic anticoagulation, and hospital-acquired pneumonia treated with antibiotic therapy. The results of this analysis were favorable in comparison with previously reported incidence rates for pressure ulcer, deep venous thrombosis, and hospital-acquired pulmonary complications in patients with similar risk factors, and suggested that a prescribed bed protocol reduces complications associated with bed rest. PMID- 20362474 TI - Geographic origin of publications in radiological journals as a function of GDP and percentage of GDP spent on research. AB - RATIONALE AND OBJECTIVES: The aim of this study was to examine the geographic origin of publications in the highest impacting radiology journals and to examine the link between the percentage of gross domestic product (GDP) spent on research by a country and the output of radiology publications. MATERIALS AND METHODS: The five highest impacting general radiology journals (according to the ISI Web of Knowledge database) were selected over a 6-year period from January 2002 to December 2007. Publications were totaled according to the country of the corresponding author. Publications (total and corrected for population size) were assessed according to the GDP of a given country and the percentage of GDP spent on research in that country. Correlation was determined using Spearman's rank. RESULTS: In total, 10,925 papers were identified. The top 10 nations produced 83.9% of the total number of papers. The United States was the most prolific country, with 41.7% of the total. The second-ranked and third-ranked countries were Germany (11.6%) and Japan (6.7%). Corrected for GDP, smaller European countries outperformed larger nations. Switzerland (0.925 publications per billion of GDP), Austria (0.694 publications per billion of GDP), and Belgium (0.648 publications per billion of GDP) produced the most papers per billion of GDP. When corrected for percentage of GDP spent on research, European countries again ranked highest, with Greece, Turkey, and Belgium having the best ratios. The percentage of GDP spent on research was positively correlated with the number of publications in high-ranking radiology journals (r = 0.603, P < .001). CONCLUSIONS: The United States is the most productive country in absolute number of publications. The flaws of using population size to compare publication output are clear, and a comparison using GDP and the percentage of GDP spent on research may give more meaningful results. When GDP is taken into consideration, smaller European countries are more productive. The importance of investment in radiologic research is emphasized by the association between increased funding of research and the number of publications in high-impacting radiology journals. PMID- 20362473 TI - Indirect inhibition of Toll-like receptor and type I interferon responses by ITAM coupled receptors and integrins. AB - An important function of immunoreceptor tyrosine-based activation motif (ITAM) coupled receptors is cross-regulation of heterologous receptor signaling, but mechanisms of cross-inhibition are poorly understood. We show that high-avidity ligation of ITAM-coupled beta2 integrins and FcgammaRs in macrophages inhibited type I interferon receptor and Toll-like receptor (TLR) signaling and induced expression of interleukin-10 (IL-10); signaling inhibitors SOCS3, ABIN-3, and A20; and repressors of cytokine gene transcription STAT3 and Hes1. Induction of inhibitors was dependent on a pathway composed of signaling molecules DAP12, Syk, and Pyk2 that coupled to downstream kinases p38 and MSKs and required integration of IL-10-dependent and -independent signals. ITAM-induced inhibitors abrogated TLR responses by cooperatively targeting distinct steps in TLR signaling. Inhibitory signaling was suppressed by IFN-gamma and attenuated in inflammatory arthritis synovial macrophages. These results provide an indirect mechanism of cross-inhibition of TLRs and delineate a signaling pathway important for deactivation of macrophages. PMID- 20362475 TI - The influence of socio-economic deprivation on rates of major lower limb amputation secondary to peripheral arterial disease. AB - OBJECTIVES: To investigate a hypothesised link between socio-economic deprivation and rates of major lower limb amputation within the catchment of a district general hospital in the United Kingdom. DESIGN: An analysis of a demographic database collated using patients identified by the OPCS codes for lower limb amputations. MATERIALS: All patients undergoing a lower limb amputation as a result of peripheral vascular disease, as identified by ICD-10 code, between January 2003 and January 2009 were included in the study. METHODS: A case-control study was undertaken, comparing the Index of Multiple Deprivation 2007 (IMD) scores of major lower limb amputees, to those of the catchment population. Multivariate analysis was not undertaken. RESULTS: A total of 327 patients underwent 445 lower limb amputations during the 6-year period. A comparative plot of cumulative frequency of IMD score in the catchment and amputation groups indicates greater numbers of major amputations in more deprived postcodes (P=0.004). The catchment population was further divided into population-matched deprivation quintiles. A significant increase in the number of amputations occurred in the two most deprived quintiles (OR (95%CI)=1.654 (1.121-2.440), P=0.011) CONCLUSIONS: This study indicates a positive association between increasing social deprivation and rates of lower limb amputation. If the most deprived quintiles are combined, this increase in amputation rates is approximately 65%. This inequity should be further investigated, and consideration given to targeted care within areas of greater social deprivation. PMID- 20362476 TI - Long-term results after transfemoral venous thrombectomy for iliofemoral deep venous thrombosis. AB - OBJECTIVE: In patients presenting with extensive venous thrombosis affecting the pelvic veins, transfemoral venous thrombectomy has been suggested as an effective treatment in selected patients. We present our experience of this technique as well as its long-term results. PATIENTS AND METHODS: Between January 1998 and January 2008, a total of 83 patients underwent transfemoral venous thrombectomy in our Department of Vascular Surgery. In 22 cases, this was combined with angioplasty and stenting of an iliac vein stenosis. Isolated intra-operative thrombolysis was performed in eight cases to treat deep venous thrombosis (DVT) affecting veins distal to the common femoral vein. All patients suffered from a DVT involving the pelvic veins. A DVT involving all venous segments from the pelvis to the calf was present in 63% of cases. Patients were followed up at 3 months, 6 months and yearly thereafter by clinical and duplex ultrasound examination. RESULTS: In all patients, the procedure was successful in achieving re-canalisation of the pelvic veins at the end of the operation. Perioperatively, there was no mortality and there was no case of clinically detected pulmonary embolism. Life-table analysis showed that, after a mean duration of 60 months following treatment, approximately 75% of the treated venous segments remained patent. Moderate post-thrombotic syndrome (PTS; clinical severity, etiology, anatomy and pathophysiology (CEAP) C2-C4) was present in 20% of cases; severe PTS (CEAP C5 and C6) did not occur in any of the treated patients. CONCLUSIONS: It is safe and effective to treat extensive iliofemoral DVT using transfemoral venous thrombectomy and this prevents the development of severe PTS in the long term. The procedure is only feasible in a subset of patients with DVT, depending on the extent and the age of the thrombosis. PMID- 20362477 TI - Photoplethysmographic venous refilling times following ultrasound guided foam sclerotherapy for symptomatic superficial venous reflux: relationship with clinical outcomes. AB - INTRODUCTION: Digital photoplethysmography (PPG) provides an inexpensive, reproducible, quantitative, non-invasive assessment of lower limb venous function. AIM: To examine the relationship between venous refilling time (VRT) and severity of venous disease, and also between changes in VRT and symptomatic improvement after ultrasound guided foam sclerotherapy (UGFS) for symptomatic superficial venous reflux (SVR). METHODS: Prior to and 6 months after UGFS, 246 patients (317 limbs) completed a symptom questionnaire, underwent duplex ultrasonography and clinical assessment, and VRT measurement by digital PPG. Health related quality of life (HRQL) questionnaires were also completed. RESULTS: Median VRT improved from 11 to 31 s (P < 0.0005, Wilcoxon Signed Ranks). Abnormal VRT (<20 s) correlated well with the presence of SVR on duplex (sensitivity 75%, specificity 94%). Pre-treatment there was a significant relationship between reducing VRT and increasing CEAP clinical grade (P < 0.0005, chi(2)), extent of SVR on duplex (P < 0.0005) and a non-significant relationship with overall increasing symptom severity (P = 0.097). Relief of all symptoms was more likely when there was normalisation of VRT after treatment (80% vs. 65%, P < 0.0005, chi(2)). Pre-treatment VRT correlated with both generic physical (r = 0.428, P = 0.002) and disease-specific (r = -0.413, P = 0.003, Spearman's rank) HRQL. CONCLUSIONS: UGFS for SVR improves VRT measured by digital PPG and that improvement correlates with symptom relief. PMID- 20362478 TI - TEThered to Runx: novel binding partners for runx factors. AB - RUNX transcription factors reside in the nuclear matrix where they integrate numerous signaling pathways to regulate gene expression and affect tissue development, regeneration, and tumorigenesis. An affinity purification and proteomic experiment was performed to identify novel Runx2 binding partners. The interactions between Runx2 and two nuclear factors (Ddx5 and CoAA) identified in this screen were previously described. Coactivator activator (CoAA) bound the DNA binding domain of Runx2 and prevented Runx-driven gene expression. The YxxQ motif in CoAA was required for Runx2 interactions. Members of the FET/TET family of proteins, including FUS/TLS and EWSR1, contain a similar motif and were hypothesized to interact with Runx2. Here, we provide evidence that FUS/TLS, EWSR1, and the Ewing's sarcoma t(12;21) fusion protein EWS-FLI bind Runx2 and alter its transcriptional activity. Potential roles of protein complexes containing FET/TET and RUNX family members during tumor formation and mesenchymal progenitor cell differentiation are discussed. PMID- 20362479 TI - Seroprevalence of hepatitis C virus: the first population-based study from Iran. AB - OBJECTIVE: Early studies on blood donors point to a seroprevalence of approximately 0.25% for hepatitis C virus (HCV) infection in Iran. However, the true prevalence in the general population is unknown. The objective of this study was to determine the prevalence of HCV infection in the general population of Iran. METHODS: We randomly selected 6583 subjects from three provinces in Iran for inclusion in the study. Subjects were aged between 18 and 65 years. Anti hepatitis C antibody was tested by a third-generation ELISA test. A recombinant immunoblot assay (RIBA) test was used to confirm the results. Risk factors were recorded and a multivariate analysis was performed. RESULTS: A total of 5684 plasma samples were tested. After confirmatory tests, we found 50 cases of HCV. The overall weighted prevalence of anti-HCV was 0.5%. The rate was significantly higher in men (1.0%) than in women (0.1%). In multivariate analysis, male sex, history of intravenous drug abuse, and imprisonment were significantly associated with anti-HCV. CONCLUSIONS: We found the prevalence of HCV infection in Iran to be higher than previous estimates. It appears that the rate is rising, and in the future, hepatitis C will replace hepatitis B as the most common cause of chronic viral liver disease in Iran. PMID- 20362480 TI - [Informing a patient about surgical treatment for pelvic organ prolapse]. AB - Inform consent is a major objective in the relation patient-physician. Patient's information becomes doubt when it is insufficient. To answer to medical persons asking about patient's information, pretreatment clinical and paraclinical assessment will be discussed. Reflexion delay, surgical alternative therapy and pre-operatory examination will be exposed. Several critical situations, such as associated hysterectomy, patient's comorbidity (tobacco, obesity) or synthetic mesh reinforcement have to be well-known to inform patient about failures and outcomes. PMID- 20362481 TI - [Anal cancer and human papillomaviruses: a perspective based on the cervical cancer model]. AB - Anal cancer is a rare pathology in the general population but the incidence of this cancer has been on the rise for certain high-risk groups, such as homosexual men and immunodepressed subjects. The incidence of anal cancer is 10 times higher in the HIV-positive population than in the female population in general. Moderate to severe dysplasias (AIN2-3) are types of precancerous lesions that usually precede the appearance of the cancer. HPV16 infection is the most common (3/4 of the cases) followed by HPV18 (less than 10%). In anal cancer, HPV16 is present in over 75% of the cases. The prevalence of HPV in anal cancer is higher in women (90%) than in men (75%). Squamous cervical and anal cancers have strong similarities founded on the causal association to HPV, in particular HPV16. Recent data indicate that anti-HPV vaccination has a significant potential in preventing HPV infections, precancerous lesions, and anal cancer in the general population as well as in the high-risk groups. PMID- 20362482 TI - [Response by P. Boyer et al. to the article "Regulations for oocyte donation in France" ]. PMID- 20362483 TI - [Impact of twin gestation on the risk of postpartum stress incontinence]. AB - OBJECTIVE: To study twin pregnancy and delivery as a risk factor for developing postpartum stress urinary incontinence (SUI). PATIENTS AND METHODS: Retrospective single centre study comparing 117 patients who have delivered twins to 117 patients who have given birth to singletons, between January 2003 and December 2005 in a tertiary maternal-foetal medicine unit. The risk factors associated with the onset of postpartum SUI, its severity, and its impact on the quality of life were studied. RESULTS: Sixty patients in the twin pregnancy group and 59 in the singleton pregnancy group have answered an auto-questionnaire and were included in the study. The medium-term follow-up of the patient was 20.2 months+/ 10.1. The prevalence of SUI in the total population was 30%. The rate was significantly higher in the "twin" group (40%) than in the "singleton" group (20%) (p=0.03). Twin gestation was significantly associated with postpartum SUI for more than 20 months after delivery (OR=2.6 [1.1-5.9]). The univariate analysis found six other risk factors: prenatal urinary incontinence (OR=4.2 [1.7 10.4]), BMI greater than 30 (OR=6.3 [1.2-34.1]), labour duration greater than 8h (OR=4.8 [1.6-14.5]), fundal uterine pressure (OR=4.5 [1.1-18.3]), total intrauterine foetal weight (p=0.003), and immediate postpartum urinary incontinence (OR=12.9 [5-33.5]). DISCUSSION AND CONCLUSION: The vaginal delivery of two successive foetuses does not seem more purveyor of SUI than caesarean. In twin pregnancies, the high rate of postpartum SUI appears to be related to total intrauterine weight. PMID- 20362484 TI - [Intrauterine inseminations in women over 35: the pros]. PMID- 20362485 TI - A fatality involving an unusual route of fentanyl delivery: Chewing and aspirating the transdermal patch. AB - We recently encountered a subject who died from an uncommon misuse of a fentanyl transdermal patch, chewing, followed by complications of aspiration of the patch. We report this case to alert medical examiners to the troubling trend of increased fentanyl patch abuse and its expanding range of misuses and associated morbidities. The decedent was a 28-year-old white male with a past medical history of prescription drug abuse who was pronounced dead in the emergency department shortly after arrival. An autopsy was completed and a tough but stretchy beige foreign body was identified lodged in a mainstem bronchus. Toxicological analysis of femoral blood showed methamphetamine, fentanyl and norfentanyl concentrations of 1456, 8.6 and 1.4 ng/mL, respectively. Individuals who abuse prescription medications often modify the route of administration of the drug from the intended method. As this case demonstrates, this choice can be fatal. The novel findings include a chewed patch, aspiration of a drug patch, and combination with an illicit drug at potentially lethal blood levels for both methamphetamine and fentanyl in a novice user. PMID- 20362486 TI - An easy and fast ultrasonic selective S-alkylation of hetaryl thiols at room temperature. AB - A series of 2-alkylthio derivatives of hetaryl thiols were synthesized by selective S-alkylation with alkyl halides (bromides and iodides) with ultrasonic irradiation at room temperature. The reaction was found to be generally applicable to hetaryl thiol derivatives with different substituents in the aromatic nucleus and various alkyl halides. The reaction gives high to excellent yields of products with high purity. PMID- 20362487 TI - Cavitation milling of natural cellulose to nanofibrils. AB - Cavitation holds the promise of a new and exciting approach to fabricate both top down and bottom up nanostructures. Cavitation bubbles are created when a liquid boils under less than atmospheric pressure. The collapse process occurs supersonically and generates a host of physical and chemical effects. We have made an attempt to fabricate natural cellulose material using hydrodynamic as well as acoustic cavitation. The cellulose material having initial size of 63 micron was used for the experiments. 1% (w/v) slurry of cellulose sample was circulated through the hydrodynamic cavitation device or devices (orifice) for 6h. The average velocity of the fluid through the device was 10.81m/s while average pressure applied was 7.8 kg/cm(2). Cavitation number was found to be 2.61. The average particle size obtained after treatment was 1.36 micron. This hydrodynamically processed sample was sonicated for 1h 50 min. The average size of ultrasonically processed particles was found to be 301 nm. Further, the cellulose particles were characterized with X-ray diffraction (XRD) and differential scanning calorimetry (DSC) to see the effect of cavitation on crystallinity (X(c)) as well as on melting temperature (T(m)). Cellulose structures consist of amorphous as well as crystalline regions. The initial raw sample was 86.56% crystalline but due to the effect of cavitation, the crystallinity reduced to 37.76%. Also the melting temperature (T(m)) was found to be reduced from 101.78 degrees C of the original to 60.13 degrees C of the processed sample. SEM images for the cellulose (processed and unprocessed) shows the status and fiber-fiber alignment and its orientation with each other. Finally cavitation has proved to be very efficient tool for reduction in size from millimeter to nano scale for highly crystalline materials. PMID- 20362488 TI - Combining spatial priors and anatomical information for fMRI detection. AB - In this paper, we analyze Markov Random Field (MRF) as a spatial regularizer in fMRI detection. The low signal-to-noise ratio (SNR) in fMRI images presents a serious challenge for detection algorithms, making regularization necessary to achieve good detection accuracy. Gaussian smoothing, traditionally employed to boost SNR, often produces over-smoothed activation maps. Recently, the use of MRF priors has been suggested as an alternative regularization approach. However, solving for an optimal configuration of the MRF is NP-hard in general. In this work, we investigate fast inference algorithms based on the Mean Field approximation in application to MRF priors for fMRI detection. Furthermore, we propose a novel way to incorporate anatomical information into the MRF-based detection framework and into the traditional smoothing methods. Intuitively speaking, the anatomical evidence increases the likelihood of activation in the gray matter and improves spatial coherency of the resulting activation maps within each tissue type. Validation using the receiver operating characteristic (ROC) analysis and the confusion matrix analysis on simulated data illustrates substantial improvement in detection accuracy using the anatomically guided MRF spatial regularizer. We further demonstrate the potential benefits of the proposed method in real fMRI signals of reduced length. The anatomically guided MRF regularizer enables significant reduction of the scan length while maintaining the quality of the resulting activation maps. PMID- 20362489 TI - Transglucosidases as efficient tools for oligosaccharide and glucoconjugate synthesis. AB - Transglucosidases are highly promising enzymatic tools for glucodiversification. Instead of involving nucleotide-activated sugars as d-glucosyl donor, they use the energy of simple osidic linkages to synthesize carbohydrate derivatives. The remarkable promiscuity of these enzymes regarding the acceptor substrate offers great opportunities for novel synthetic reactions. Glucansucrases that use sucrose as donor substrate are of particular interest and have been widely utilized to produce diverse structurally controlled molecules. Besides site directed mutagenesis, recent developments in the combined use of computational protein design and molecular engineering have led to major achievements to create novel enzymes, in particular for the chemo-enzymatic synthesis of antigenic oligosaccharides. These promising results pave the way to the future development of tailored catalysts for the synthesis of glucoconjugates of pharmaceutical and nutritional interest. PMID- 20362490 TI - Synthesis of thiol capped CdS nanocrystallites using microwave irradiation and studies on their steady state and time resolved photoluminescence. AB - Synthesis of cadmium sulfide (CdS) nanocrystallites has been performed through the microwave (MW) assisted reaction of cadmium acetate with thiourea in N,N dimethylformamide (DMF) in the presence of two capping agents, 1-butanethiol and 2-mercaptoethanol. Attempts were made to control the size and size distribution of the thiol capped CdS nanocrystallites by controlling the number of MW irradiations/exposures for a fixed time (duration). The prepared nanocrystallites have been characterized by UV-vis spectroscopy, FTIR, XRD, FESEM and TEM. The peak position of the absorption band of the 1-butanethiol caped CdS nanocrystals in DMF solution shifted towards longer wavelength with the increasing number of MW exposures indicating the growth of particle size. In contrast, the peak position of absorption band for the 2-mercaptoethanol capped CdS nanocrystals remained nearly at the same wavelength and only the intensity of the absorption band increased with the increasing number of MW exposures. The observed steady state photoluminescence (visible range) of the 1-butanethiol capped CdS nanocrystals in DMF solution shifted towards higher wavelength, showing a decrease in intensity, with the increase in the number of MW exposures. Whereas in the case of 2-mercaptoethanol capped CdS nanocrystals in DMF solution, the photoluminescence peak remained nearly at the same position showing a decrease in intensity with increase in the number of MW exposures. The interesting results on the size-dependent steady state and time resolved photoluminescence (PL) of the CdS nanocrystallites are discussed in the present article. Possible application of such studies in the area of biotechnology has been mentioned. PMID- 20362491 TI - Spectroscopic and electron-transfer reactivity studies of bulky bis(N-cycloalkyl 3,5-tBu2-salicylaldiminato)copper(II) complexes: generation of uncoordinated and coordinated phenoxyl radicals. AB - This work summarizes the results of our studies on the spectral, magnetic, electrochemical and chemical redox properties of N-cycloalkyl-3,5-(t)Bu(2) salicylaldimine ligands [cycloalkyl=cyclo-C(5)H(9)(HL(1)), cyclo-C(6)H(11) (HL(2)), cyclo-C(7)H(13) (HL(3)), cyclo-C(8)H(15) (HL(4)), 1-adamantyl (HL(5)), 2 adamantyl (HL(6))] and their copper(II) complexes (1-6). The compounds have been characterized by IR, (1)H NMR, UV-vis, EPR spectroscopy, electrochemical and magnetic susceptibility measurements. The geometry of 1-6, according to their EPR (g(II) and g(II)/A(II)) and visible spectral data, exhibit a significant amount distortion from slightly distorted square-planar to pseudo-tetrahedral. The cyclic voltammetric studies of 1-6 reveal that as the extent of the tetrahedral distortion of Cu(II) center increases on going from 1 to 5, the values of Cu(II)/Cu(I) potentials became more negative. The compounds have been oxidized electrochemically and chemically and the generated relatively stable uncoordinated phenoxyl [HL(x)](*+) and coordinated Cu(II)-phenoxyl radical [1 6](*+) species have been characterized by UV/vis and EPR spectroscopy. PMID- 20362492 TI - Etiology of bronchiolitis in a hospitalized pediatric population: prospective multicenter study. AB - BACKGROUND: In 2006, bronchiolitis due to adenovirus nosocomial infections resulted in the closure of a pediatric department in northern Portugal. OBJECTIVES: To determine the etiology of bronchiolitis in northern Portugal. STUDY DESIGN: It was a prospective multicenter study on the etiology of bronchiolitis during the respiratory syncytial virus (RSV) season (November April). Children < or = 24 months of age admitted for a first wheezing episode were included. Nasopharyngeal specimens were analyzed by an indirect immunofluorescent-antibody assay (IFA) for RSV, adenovirus (HAdV), parainfluenza (PIV) 1-3 and influenza (IV) A and B and by polymerase chain reaction (PCR) or reverse transcription-PCR for the same viruses and for human metapneumovirus (hMPV), bocavirus (HBoV), rhinovirus (HRV), coronaviruses (229/E; NL63; OC43; HKU1) and enterovirus. RESULTS: During this period, 253 children were included, 249 IFA analyses and 207 PCRs were performed. IFA detected RSV in 58.1%; PCR increased it to 66.7%. IFA detected HAdV in 3.2%, PCR 10.0%. PCR detected IV A in 5; IV B in 2; PIV 1 in 6, PIV 2 in 4 and PIV 3 in 11 cases. HBoV, as single agent in 2 cases, and HRV were positive in 8 samples and hMPV in 11. With this virus panel, 19.7% remained without etiology. CONCLUSIONS: The most frequent agent was RSV, followed by HAdV. PCR can be cost-effective and more accurate than IFA, which is crucial for HAdV that may be associated with significant mortality (IFA alone did not detect 2/3 of the cases). PMID- 20362493 TI - Evaluation of a rapid, point-of-care test device for the diagnosis of hepatitis C infection. AB - BACKGROUND: Despite considerable evolution in the quality of laboratory-based testing for detection of HCV, the availability of rapid, point-of-care tests may increase diagnoses by increasing opportunities for testing outside of traditional laboratory settings. OBJECTIVES: We evaluated the performance of a new, rapid HCV test that can be used with venous blood, finger stick blood, serum, plasma, or oral fluid and compared it to FDA-approved laboratory methods. STUDY DESIGN: HCV positive subjects as well as subjects at low risk for HCV were tested with the rapid test using all 5 specimen types and results compared to FDA-approved laboratory methods. In addition, performance was assessed in commercially available seroconversion panels. RESULTS: Sensitivity and specificity of the rapid test was equivalent to laboratory EIA and performance was comparable across all 5 specimen types. CONCLUSIONS: The OraQuick HCV Rapid Antibody Test appears suitable as an aid in the diagnosis of HCV infection. PMID- 20362494 TI - Human coronaviruses are uncommon in patients with gastrointestinal illness. AB - BACKGROUND: Coronaviruses infect numerous animal species causing a variety of illnesses including respiratory, neurologic and enteric disease. Human coronaviruses (HCoV) are mainly associated with respiratory tract disease but have been implicated in enteric disease. OBJECTIVES: To investigate the frequency of coronaviruses in stool samples from children and adults with gastrointestinal illness by RT-PCR. STUDY DESIGN: Clinical samples submitted for infectious diarrhea testing were collected from December 2007 through March 2008. RNA extraction and RT-PCR was performed for stools negative for Clostridium difficile using primer sets against HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. Clinical data from samples positive for coronaviruses were reviewed and recorded. RESULTS: Samples from 479 patients were collected including 151 pediatric (< or = 18 years), and 328 adults (>18 years). Of these samples, 4 patients (1.3%, 2 adult; 2 pediatric) screened positive for the presence of a coronavirus. All detected coronaviruses were identified as HCoV-HKU1. No stools screened positive for either HCoV-229E, HCoV-NL63 or HCoV-OC43. All HCoV-HKU1 positive samples occurred between mid-January to mid-February. Clinical manifestations from HCoV HKU1 positive patients included diarrhea, emesis and respiratory complaints. Three (75%) patients were admitted to the hospital with a median length of stay of 6 days. CONCLUSIONS: Coronaviruses as a group are not commonly identified in stool samples of patients presenting with gastrointestinal illness. HCoV-HKU1 can be identified in stool samples from children and adults with gastrointestinal disease, with most individuals having respiratory findings as well. No stool samples screened positive for HCoV-NL63, HCoV-229E, or HCoV-OC43. PMID- 20362495 TI - Predictors of severe manifestations in a cohort of adult dengue patients. AB - BACKGROUND: Key symptoms observed during the febrile phase of dengue may identify patients who are likely to progress to severe disease. OBJECTIVES: To test this hypothesis, we examined the relationships between symptoms reported by patients at presentation and the development of severe outcomes. STUDY DESIGN: Retrospective analysis of data recorded prospectively in 560 adult dengue patients admitted to an emergency department. A logistic regression analysis was used to quantify the association between symptoms reported at presentation and outcome. RESULTS: Plasma leakage was observed in 95 patients (17%), severe thrombocytopenia (platelet counts <20 x 10(9)/L) in 93 patients (16.6%) and acute hepatitis in 42 patients (7.5%). Severe thrombocytopenia developed in 57% of patients with plasma leakage and 40.5% of patients with hepatitis. Patients who developed a plasma leakage syndrome were older, mainly male, and reported more often an abdominal pain and a cough. Diarrhea and taking paracetamol >60 mg/kg/day before admission were associated with the development of acute hepatitis. Seven patients died. The mortality rate was 6/95 (6.3%) in patients who developed plasma leakage, 3/42 (7.1%) in patients who developed hepatitis, 5/93 (5.4%) in patients with severe thrombocytopenia, and 3/12 (25%) in the patients who demonstrated together all these severe manifestations. CONCLUSION: Plasma leakage, severe thrombocytopenia and acute hepatitis identified subgroups of adult dengue patients with increased mortality rates. Key symptoms reported by the patients at presentation such as abdominal pain, cough or diarrhea were significantly associated with the development of severe manifestations and should be considered as warning signs. PMID- 20362496 TI - Human cytomegalovirus (HCMV) genotype populations in immunocompetent individuals during primary HCMV infection. AB - BACKGROUND: Immunocompetent individuals can harbor multiple human cytomegalovirus (HCMV) genotypes. However, little is known about the genotype populations acquired during primary HCMV infection. OBJECTIVE: The aim of this study was to assess the HCMV genotype populations present in the blood of non immunocompromised patients experiencing primary HCMV infection. STUDY DESIGN: HCMV glycoprotein B (gB), glycoprotein H (gH), and UL10 genotyping was performed on HCMV-positive serum samples of 36 immunocompetent patients during primary infection by sensitive gB- and gH-genotype-specific real-time-PCR assays and by UL10 sequencing. RESULTS: In all cases only one gB-gH-UL10 genotype was detected. In contrast, mixed-genotype infections were found in 4 of 14 immunocompetent patients experiencing HCMV reactivation/reinfection (P=0.004). CONCLUSION: Thus, the data support the presumption that multiple HCMV genotypes in immunocompetent individuals are often a result of serial reinfection rather than primary coinfection with different strains. PMID- 20362497 TI - Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers. AB - OBJECTIVE: Diffusion tensor imaging (DTI) recently identified structural abnormalities of corticomotoneurons in asymptomatic copper/zinc superoxide dismutase-1 (SOD-1) gene mutation carriers. The potential existence of longstanding corticomotoneuronal dysfunction would clearly have consequences for the medical management of asymptomatic SOD-1 mutation carriers. To clarify this unexpected finding, DTI techniques were combined with threshold tracking transcranial magnetic stimulation (TMS) to assess the anatomical and functional integrity of corticomotoneurons in asymptomatic SOD-1 mutation carriers. METHODS: TMS studies were undertaken using a 90 mm circular coil on seven asymptomatic SOD 1 mutation carriers and results were compared to 62 healthy controls. DTI studies were carried out using a 3T magnetic resonance device in the same asymptomatic SOD-1 mutation carriers. Results were compared to age-matched healthy controls. RESULTS: In contrast to previous findings, there were no significant differences in fractional anisotropy (SOD-1 mutation carriers, 0.62+/-0.01; controls, 0.61+/ 0.02, P=0.2) and trace apparent diffusion coefficient (SOD-1 mutation carriers, 0.003+/-0.0001; controls, 0.003+/-0.0001) in asymptomatic SOD-1 mutation carriers. Of further relevance, there were no significant differences in short interval intracortical inhibition (SOD-1 mutation carriers, 7.9+/-3.4%; controls, 8.5+/-1.1%, P=0.26), intracortical facilitation (P=0.5), MEP amplitude (P=0.44), resting motor threshold (P=0.36) and cortical silent period duration (P=0.29). CONCLUSIONS: Combined anatomical and functional modalities established normal integrity of corticomotoneurons in asymptomatic SOD-1 mutation carrier subjects. SIGNIFICANCE: Additional factors other than simply SOD-1 mutation expression are required to trigger cortical hyperexcitability and neurodegeneration in FALS. PMID- 20362498 TI - Is the brain a good marathon runner? PMID- 20362500 TI - Cortical sources of EEG rhythms are abnormal in down syndrome. AB - OBJECTIVE: Previous studies have been inconclusive whether dominant resting state alpha rhythms are greater or lower in amplitude in subjects with Down syndrome (DS) when compared to control subjects, ample resting alpha rhythms being considered as a reflection of good mechanisms of cortical neural synchronization. Here we tested the hypothesis that when the effects of head volume conduction are taken into account by the normalization of the cortical sources of resting alpha rhythms, these sources are lower in amplitude in DS subjects than in controls in line with typical findings in Alzheimer's disease patients. METHODS: Eyes-closed resting electroencephalographic (EEG) data were recorded in 45 DS subjects (25 males; mean age of 22.8years+/-0.7 standard error of mean (SEM)) and in 45 age matched cognitively normal subjects (25 males; mean age of 22.4years+/-0.5 SEM). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). Cortical EEG sources were estimated by low resolution electromagnetic tomography (LORETA) and normalized across all voxels and frequencies. RESULTS: Central, parietal, occipital, and temporal cortical sources of resting alpha and beta rhythms were lower in amplitude in the DS than control subjects, whereas the opposite was true for occipital delta cortical sources. A control analysis on absolute source values showed that they were globally larger in amplitude across several frequency bands in DS than control subjects. CONCLUSIONS: These results suggest that normalized cortical sources of alpha rhythms are lower in amplitude in DS than control subjects, as it is typically found in Alzheimer's disease. SIGNIFICANCE: DS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition. PMID- 20362499 TI - Suppression of deep brain stimulation artifacts from the electroencephalogram by frequency-domain Hampel filtering. AB - OBJECTIVE: Currently, electroencephalography (EEG) cannot be used to record cortical activity during clinically effective DBS due to the presence of large stimulation artifact with components that overlap the useful spectrum of the EEG. A filtering method is presented that removes these artifacts whilst preserving the spectral and temporal fidelity of the underlying EEG. METHODS: The filter is based on the Hampel identifier that treats artifacts as outliers in the frequency domain and replaces them with interpolated values. Performance of the filter was tested with a synthesized DBS signal and actual data recorded during bilateral monopolar DBS. RESULTS: Mean increases in signal-to-noise ratio of 7.8dB for single-frequency stimulation and 13.8dB for dual-frequency stimulation are reported. Correlation analysis between EEG with synthesized artifacts and artifact-free EEG reveals that distortion to the underlying EEG in the filtered signal is negligible (r(2)>0.99). CONCLUSIONS: Frequency-domain Hampel filtering has been shown to remove monopolar DBS artifacts under a number of common stimulation conditions used for the treatment of Parkinson's disease. SIGNIFICANCE: Application of frequency-domain Hampel filtering will allow the measurement of EEG in patients during clinically effective DBS and thus may increase our understanding of the mechanisms of action of this important therapeutic intervention. PMID- 20362501 TI - Xyrem (sodium oxybate) postmarketing adverse event reporting system. PMID- 20362502 TI - Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. AB - OBJECTIVE: To estimate the prevalence of Obstructive Sleep Apnea Syndrome (OSAS), using current clinical and epidemiological techniques, among the adult population of Sao Paulo, Brazil. METHODS: This population-based survey used a probabilistic three-stage cluster sample of Sao Paulo inhabitants to represent the population according to gender, age (20-80 years), and socio-economic status. Face-to-face interviews and in-lab full-night polysomnographies using a nasal cannula were performed. The prevalence of OSAS was determined according to the criteria of the most recent International Classification of Sleep Disorders (ICDS-2) from American Academy of Sleep Medicine (2005). RESULTS: A total of 1042 volunteers underwent polysomnography (refusal rate=5.4%). The mean age+/-SD was 42+/-14 years; 55% were women and 60% had a body mass index>25 kg/m(2). OSAS was observed in 32.8% of the participants (95% CI, 29.6-36.3). A multivariate logistic regression model identified several independent and strong associations for the presence of OSAS: men had greater association than women (OR=4.1; 95% CI, 2.9 5.8; P<0.001) and obese individuals (OR=10.5; 95% CI, 7.1-15.7; P<0.001) than individuals of normal weight. The adjusted association factor increased with age, reaching OR=34.5 (95% CI, 18.5-64.2; P<0.001) for 60-80 year olds when compared to the 20-29 year old group. Low socio-economic status was a protective factor for men (OR=0.4), but was an associated factor for women (OR=2.4). Self-reported menopause explained this increased association (age adjusted OR=2.1; 95% CI, 1.4 3.9; P<0.001), and it was more frequent in the lowest class (43.1%) than either middle class (26.1%) or upper class (27.8%) women. CONCLUSIONS: This study is the first apnea survey of a large metropolitan area in South America identifying a higher prevalence of OSAS than found in other epidemiological studies. This can be explained by the use of the probabilistic sampling process achieving a very low polysomnography refusal rate, the use of current techniques and clinical criteria, inclusion of older groups, and the higher prevalence of obesity in the studied population. PMID- 20362503 TI - Sleep-disordered breathing and cardiac autonomic modulation in children. AB - OBJECTIVES: To investigate the adverse cardiac autonomic effects of sleep disordered breathing (SDB) in a large population-based sample and a clinical sample of children. METHODS: Subjects included a population-based sample of 700 and a clinically diagnosed sample of 43 SDB children. SDB was defined based on an apnea hypopnea index (AHI) 1 during one night of polysomnography. Cardiac autonomic modulation was measured by heart rate variability (HRV) analysis of the beat-to-beat RR interval data collected during polysomnography. RESULTS: The mean (SD) age was 112 (21) months, with 49% male and 25% non-white. About 73.0% had AHI<1 (no SDB), 25.8% had 1-5 AHI (mild SDB), and 1.2% had 5 AHI (moderate SDB). Among individuals with moderate SDB in the population-based sample and the clinically diagnosed SDB patients, the mean (SE) of HRV-high frequency power (HF) was significantly lower compared to children without SDB [6.00 (0.32) and 6.24 (0.14), respectively, vs. 6.68 (0.04) ms(2), p<0.05 and p<0.01, respectively], whereas the low frequency power to high frequency power ratio (LF/HF) was significantly higher [1.62 (0.20) and 1.74 (0.09), respectively, vs. 0.99 (0.02), both p<0.01)]. CONCLUSIONS: SDB in healthy young children and in clinical patients is significantly associated with impaired cardiac autonomic modulation, i.e., sympathetic overflow and weaker parasympathetic modulation, which may contribute to increased risk of acute cardiac events in persons with SDB, even before reaching the "high risk age." PMID- 20362504 TI - Airborne endotoxin associated with particles of different sizes and affected by water content in handled straw. AB - High exposures to endotoxin are observed in environments where organic materials are handled and lower exposures are found in e.g. indoor air. Inhaled endotoxin contributes significantly to the induction of airway inflammation and dysfunction. The size of an inhaled particle influences the deposition in the airways and the following health symptoms. The objective is to characterise the distribution of endotoxin on airborne particles of different sizes in straw storage halls with high exposure and in other environments with lower exposure levels to endotoxin. Furthermore we have studied the influence of water content of handled straw on the size distribution of endotoxin containing particles. Total, inhalable, thoracic and respirable endotoxin and particles have each been quantified in aerosols from boiler rooms and straw storage halls at 24 power plants, including 21 biofuel plants. Inhalable, thoracic and respirable endotoxin have been quantified in aerosols from offices and outdoor air. The endotoxin concentration was higher in airborne thoracic dust than in airborne 'total dust'. The median respirable fraction in the straw storage halls, boiler rooms at biofuel plants, boiler rooms at conventional plants, offices and outdoors was respectively 42%, 9%, 19%, 24% and 34%. Thoracic endotoxin per number of thoracic particles was higher than respirable endotoxin per number of respirable particles at the biofuel plants. In straw storage halls the fraction of endotoxin of respirable size was highest on the days with lowest water content in the received straw. Furthermore the exposures to all endotoxin fractions were highest on days with the lowest water content in the received straw. In conclusion the highest exposures and concentrations of endotoxin occur or tend to occur from thoracic dust. A high variation in endotoxin concentrations and in fractions of respirable or thoracic size is found in the different working areas. This is important in the risk assessment and makes attempts to influence the endotoxin exposure a possibility. Water content in straw affected the concentration, exposure level and size distribution of airborne endotoxin. PMID- 20362505 TI - Coarctation of the aorta presenting as spontaneous subarachnoid haemorrhage in the absence of cerebral aneurysm: a report of a rare clinical entity. AB - Subarachnoid haemorrhage (SAH) is a common neurologic event characterised by bleeding into the space immediately surrounding the brain. In non-traumatic SAH, the predominant cause is aneurysmal rupture of the cerebral vasculature. A significant number occur in the absence of vascular anomalies. This report describes a case of a 35-year-old male who presented with a subarachnoid haemorrhage in the absence of intracranial aneurysm. Subsequent workup demonstrated severe proximal hypertension due to congenital aortic coarctation as the cause of this event. This case demonstrates the importance of considering congenital abnormalities when evaluating patients with cerebrovascular events in the absence of common aetiologies. PMID- 20362506 TI - Management of atrial fibrillation in the acute setting--findings from an Australasian survey. AB - Acute atrial fibrillation (AF) is a commonly encountered problem in emergency departments. In this web-based questionnaire study, 242 emergency physicians and 77 cardiologists in Australasia managed seven hypothetical acute AF scenarios. We found wide variation in practice within and between specialties, and a significant proportion of responses inconsistent with best practice guidelines. PMID- 20362508 TI - Targeted therapies for rare gynaecological cancers. AB - Some gynaecological cancers are uncommon, such as sex cord-stromal tumours, malignant germ-cell tumours, vulvar carcinoma, melanoma of the female genital tract, clear-cell carcinoma of the ovary and endometrium, neuroendocrine tumours of the cervix, and gestational trophoblastic neoplasia. All these cancers have different clinicopathological characteristics, suggesting different molecular biological pathogeneses. Despite aggressive treatment, some cancers recur or respond poorly to therapy. Comprehensive knowledge of the molecular biology of each cancer might help with development of novel treatments that maximise efficacy and minimise toxic effects. Targeted therapy is a new treatment strategy that has been investigated in various tumours in clinical and laboratory settings. Since these cancers are rare and large clinical trials are difficult to do, molecular biological techniques might allow rapid proof-of-principle experiments in few patients. Novel targeted agents either alone or in combination with other treatments offer promising therapeutic options. PMID- 20362507 TI - Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. AB - BACKGROUND: Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. METHODS: Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. FINDINGS: Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group. INTERPRETATION: Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs. FUNDING: Novartis Pharmaceuticals and Pfizer Inc. PMID- 20362509 TI - Advances in lupus stemming from the parent-into-F1 model. AB - The parent-into-F1 model has led to important advances in our understanding of lupus. Here, we review the work in murine lupus that elucidated the role of T cells and supported the conclusion that the parent-into-F1 model of induced lupus compares favorably with de facto gold standard spontaneous models of lupus. Then we focus on recent work in parent-into-F1 mice, which has yielded novel insights into unresolved controversies, such as the role of apoptosis in the pathogenesis of lupus and lupus in patients receiving TNF blockade. Finally, the review considers the evidence that supports a potential role for CD8 T cells, both cytotoxic and memory cells, in mediating disease remission. PMID- 20362510 TI - Hyperandrogenism alters intraovarian parameters during early folliculogenesis in mice. AB - This study aimed to investigate how hyperandrogenism affects early folliculogenesis. Hyperandrogenism was induced in prepuberal female BALB/c mice by daily s.c. injection of dehydroepiandrosterone (60 mg/kg body weight in 0.1 ml sesame oil) for 10 consecutive days. Although hyperandrogenism increased the growth rate of primary follicles, it also increased ovarian oxidative stress (evaluated by the increase in lipid peroxidation, the decrease in superoxide dismutase activity and the fact that glutathione content was not modified). By using the annexin V/cytometry assay it was found that the excess of androgens decreased viable ovarian cells and increased early apoptotic ones. The increased lipid peroxidation induced enhanced ovarian prostaglandin E production. In addition, hyperandrogenism increased the number of T lymphocytes that infiltrate ovarian tissue and modified their phenotype (decreased CD4+ or helper and increased the suppressor/cytotoxic CD8+). The excess of androgens decreased the ovarian expression of the long isoform of leptin receptor (Ob-Rb, the only isoform expressed in the ovarian tissue) when compared with controls. All these alterations increased serum concentrations of oestradiol, a pro-apoptotic agent. It is concluded that the excess of androgens impairs early follicular development by modulating some endocrine and immune parameters that are either directly or indirectly related to follicular atresia. PMID- 20362511 TI - Cumulative live-birth delivery after IVF/ICSI since the progressive introduction of single-embryo transfer. AB - The only way to decrease the incidence of multiple pregnancies in the IVF/intracytoplasmic sperm injection (ICSI) population is to introduce single embryo transfer (SET). This study investigated the impact of the progressive introduction of SET for the whole IVF/ICSI population from the patients' point of view by calculating the cumulative live-birth delivery rate. During a 5-year period (2001-2005), the outcome of 2164 cycles with oocyte aspiration in 1047 patients was analysed. A subanalysis was made to calculate the additional effect of frozen-thawed cycles. Survival analysis was performed with the Kaplan-Meier method and the endpoint was live-birth delivery. In this 5-year period, the cumulative live-birth delivery rate per patient was 51% after three IVF/ICSI cycles and 58% after six cycles. With a more permissive method of survival analysis, these results were 64% and 85%, respectively. The additional effect of the frozen-thawed cycles since reimbursement was only 5%. SET was progressively introduced in this period leading to a twin live-birth delivery rate of only 6.7%. It is concluded that a favourable outcome was observed for the cumulative live-birth delivery rate since the introduction of SET but with a disappointing additional effect of the frozen-thawed cycles. PMID- 20362512 TI - The significance of the number of CGG repeats and autoantibodies in premature ovarian failure. AB - The objective of this study was to determine whether there was a threshold for the number of CGG repeats in the FMR1 (fragile X) gene in premature ovarian ageing and premature ovarian failure and to investigate the association of this sequence with serum concentrations of anti-Mullerian hormone (AMH), inhibin B, anti-thyroid and anti-adrenal autoantibodies. In this prospective randomized controlled preliminary study, the number of triple CGG repeats and serum concentrations of FSH, AMH and aforementioned autoantibodies were evaluated in 79 women who were younger than 40 years old. FSH concentrations were between 12 and 50 IU/ml (premature ovarian ageing) in 30 women and were higher than 50 IU/ml (premature ovarian failure) in nine women; FSH concentrations were normal in 40 women. All women whose FSH concentrations were higher than 12 IU/ml had CGG repeats greater than 30. No women whose FSH concentrations were normal had a repeat number above 30. There was no significant relationship between the levels of antibodies and either CGG repeat numbers or FSH concentrations. In conclusion, the number of CGG repeats between 30 and 40 might be used to predict premature ovarian ageing and premature ovarian failure in infertile women. PMID- 20362513 TI - Does mitochondrial DNA have a protective role in stroke? PMID- 20362514 TI - Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: a genetic association study. AB - BACKGROUND: Genetic factors have a role in the pathogenesis of ischaemic stroke, but the main genes involved have yet to be defined. Mitochondrial mechanisms have been implicated in the pathophysiology of acute stroke, but the role of mitochondrial DNA (mtDNA) has not been comprehensively studied. We investigated whether there is an association between mtDNA haplotypes and incidence of stroke. METHODS: The major European mtDNA haplogroups were identified in two independent subpopulations (n=950) from a study of occurrence of transient ischaemic attack (TIA) and ischaemic stroke and were compared with those of patients with acute coronary syndromes from the same populations (n=340) and with those of independent population controls (n=2939). FINDINGS: The presence of mtDNA sub haplogroup K was significantly less frequent in patients with TIA or stroke than in controls in both subpopulations separately and in a pooled analysis (odds ratio 0.54, 95% CI 0.39-0.75, p<0.00001). This association remained highly significant after adjustment for multiple haplogroup comparisons. The association was significant for patients with TIA and stroke separately and was independent of known risk factors, but was not found for patients with acute coronary events. The mtDNA sub-haplogroup K was present in 8.7% of the total UK population controls and therefore confers a 4.0% (95% CI 2.2-5.7) reduction in population attributable risk of TIA and stroke. INTERPRETATION: Genetic variation of mtDNA sub-haplogroup K is an independent determinant of risk of cerebral, but not coronary, ischaemic vascular events. These findings implicate mitochondrial mechanisms in the aetiology of ischaemic stroke and provide a new means for the identification of individuals with a high susceptibility of developing ischaemic stroke. PMID- 20362515 TI - Obstetric performance following an induced abortion. AB - Abortion has been legalised in most of the Western world for the past four decades. In areas where abortion practices are legal and easy to access, the risk of short-term complications is very low. As most women requesting induced abortion (IA) are young, potential adverse effects on subsequent reproductive function are important to them. This review investigates obstetric performance following IA and highlights methodological problems associated with research in this area. Some data suggest that IA may be linked with an increased risk of low birth weight, miscarriage and placenta previa but could be protective for pre eclampsia. Current evidence also suggests an association between IA and pre-term birth. Large prospective cohort studies, which permit meaningful subgroup analyses, are needed to provide definitive answers on outcomes following alternative methods of IA and the impact of gestational age at abortion on future obstetric outcomes. PMID- 20362516 TI - Mice with DNA repair gene Ercc1 deficiency in a neural crest lineage are a model for late-onset Hirschsprung disease. AB - The Ercc1 gene is essential for nucleotide excision repair and is also important in recombination repair and the repair of interstrand crosslinks. We have previously used a floxed Ercc1 allele with a keratinocyte-specific Cre recombinase transgene to inactivate Ercc1 in the epidermal layer of the skin and so generate a mouse model for UV-induced non-melanoma skin cancer. Now, in an attempt to generate a model for UV-induced melanoma, we have used the floxed Ercc1 allele in combination with a Cre transgene under the control of the tyrosinase gene promoter to produce mice with Ercc1-deficient melanocytes that are hypersensitive to UV irradiation. These animals developed normally, but died when 4-6 months old with severe colonic obstruction. Melanocytes are derived from the neural crest and the tyrosinase promoter is also expressed in additional neural crest-derived lineages, including the progenitors of the parasympathetic nervous system that innervates the gastrointestinal tract and controls gut peristalsis. A functional enteric nervous system developed in floxed Ercc1 mice with the tyrosinase Cre transgene, but was found to have degenerated in the colons of affected mice. We suggest that accumulating unrepaired endogenous DNA damage in the Ercc1-deficient colonic parasympathetic ganglia leads to the degeneration of this network and results in a colonic obstructive disorder that resembles late-onset Hirschsprung disease in man. PMID- 20362517 TI - Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid. AB - BACKGROUND: Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated. METHODS: The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2-->87.0 (SA) and m/z 311.2--> 90.0 ((13)C(3)-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients' samples with known differences in SA metabolites like meningitis (n=6), brain tumour (n=2), leukaemia (n=5), and Salla disease (n=1). RESULTS: Limit of detection (LOD) was 0.54 microM for FSA and 0.45 mM for TSA. Intra- and inter-assay variation for FSA (21.8 microM) were 4.8% (n=10) and 10.4% (n=40) respectively. Intra- and inter-assay variation for TSA (35.6 microM) were 9.7% (n=10) and 12.8% (n=40) respectively. Tested patients showed values of TSA above established reference value. CONCLUSION: The validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses. PMID- 20362518 TI - Study of the mechanism of interaction of antibody (IgG) on two mixed mode sorbents. AB - Purification of target proteins from a crude biological mixture containing proteins, peptides and other biomolecules is the chromatographic challenge. Mixed mode chromatography offers additional selectivities to improve the overall productivity of commercial bioprocesses with novel chromatographic sorbents being introduced to overcome the problem. HEA HyperCel (n-hexyl amine) and PPA HyperCel (phenyl propyl amine) are industry scalable mixed mode chromatography sorbents where both hydrophobic and electrostatic interactions are predominant. Our study focuses on understanding the underlying mechanism of interaction of protein with the sorbent. Parameters like buffer conditions, pH and temperature were tuned to study the adsorption and desorption conditions of the protein. Dynamic binding capacity of HEA HyperCel and PPA HyperCel sorbents was studied with human IgG as a model protein. Our study shows that, in HEA the interaction of IgG to the sorbent is predominantly hydrophobic as the binding is enhanced (50-60 mg/ml of sorbent) by presence of salt in buffer and increase in temperature. Binding capacity of PPA is 50-60 mg/ml of sorbent irrespective of temperature effect and/or the presence of salt. The chromatographic experiments show that the interaction could be hydrophobic or ionic or some charge transfer mechanism depending upon the buffer conditions. PMID- 20362519 TI - Capillary electrophoresis separation and matrix-assisted laser desorption/ionization mass spectrometry characterization of bovine serum albumin fluorescein isothiocyanate conjugates. AB - A protocol using enzymatic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and capillary electrophoresis with laser induced fluorescence detection (CE-LIF) for the investigation of the binding of the fluorescent contact allergen fluorescein isothiocyanate (FITC) to the 66 kDa large protein bovine serum albumin (BSA), as a model system for protein-hapten binding in the skin, is presented. Mass spectra of BSA-FITC digestions, using trypsin and chymotrypsin, respectively, provided sequence coverage of 97%. To investigate the number of FITC-bound peptides using CE-LIF separation, three different buffer salts at four different pH levels were evaluated. The use of 20 mM sodium citrate pH 6.5 as well as 20 mM sodium phosphate pH 6.5 or pH 7.5 as background electrolyte revealed high numbers of peptides with at least one bound FITC. The effect of the electrolyte counter ion on MALDI-MS was investigated and was found to have effect on the MALDI spectra signal-to-noise (S/N) at 50 mM but not at 10 mM. Of the 60 theoretical FITC binding sites in BSA this MALDI-MS protocol presents 30 defined, 28 possible and 2 non-binding sites for FITC. PMID- 20362520 TI - Body composition and wages. AB - This paper examines the relationship between body composition and wages in the United States. We develop measures of body composition--body fat (BF) and fat free mass (FFM)--using data on bioelectrical impedance analysis (BIA) that are available in the National Health and Nutrition Examination Survey III and estimate wage models for respondents in the National Longitudinal Survey of Youth 1979. Previous research uses body size or BMI as measures of obesity despite a growing concern that they do not distinguish between body fat and fat-free body mass or adequately control for non-homogeneity inside the human body. Therefore, measures presented in this paper represent a useful alternative to BMI-based proxies of obesity. Our results indicate that BF is associated with decreased wages for both males and females among whites and blacks. We also present evidence suggesting that FFM is associated with increased wages. We show that these results are not the artifacts of unobserved heterogeneity. Finally, our findings are robust to numerous specification checks and to a large number of alternative BIA prediction equations from which the body composition measures are derived. PMID- 20362521 TI - [Secondary hyperparathyroidism in advanced prostate cancer]. AB - BACKGROUND AND OBJECTIVE: High parathyroid hormone (PTH) concentrations are associated with increased bone resorption and bone matrix degradation. Some studies show elevated PTH concentrations and hypocalcemia in patients with advanced prostate carcinoma, although the pathophysiological significance of these findings is not well defined. MATERIALS AND METHODS: We performed a retrospective study of 60 patients diagnosed with advanced prostate cancer (44 nonmetastatic and 16 metastatic) treated with androgen deprivation. In all patients, PTH, calcium, phosphorus, 25 (OH) vitamin D and prostate-specific antigen (PSA) were determined. Bone scintigraphy had previously been performed. RESULTS: In patients with bone metastases, mean concentrations were as follows: calcium 9.19 mg/dl, phosphorus 3.47 mg/dl, 25 (OH) vitamin D 13.85 ng/ml, PTH 66.8 pg/ml and total PSA 101.27 ng/ml. For those without bone metastases, the results were calcium 9.39 mg/dl, phosphorus 3.38 mg/dl, 25 (OH) vitamin D 20.50 ng/ml, PTH 52.23 pg/ml and total PSA 2.52 ng/ml. PTH levels were significantly higher in patients with prostate cancer and bone metastases than in those without metastases (p=0.03). Vitamin D levels were also significantly lower in this group (p=0.03). There were no differences in other values. CONCLUSIONS: The present study found increased PTH concentrations in patients with advanced prostate cancer. This finding could be useful to predict disease progression. PMID- 20362522 TI - LCT-13910C>T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy. AB - BACKGROUND: The activity of epithelial lactase (LCT) associates with a polymorphism 13910 bp upstream the LCT-encoding gene (LCT-13910C>T). The relationship between LCT-13910C>T polymorphism and risk for colorectal cancer is unclear. AIMS: We examined the relationship between the LCT-13910C>T polymorphism causing lactose intolerance and risk for colorectal cancer/polyps onset in the Italian population. PATIENTS AND METHODS: 793 subjects (306 with colorectal cancer, 176 with polyps and 311 controls) were genotyped for the LCT-13910C>T variant by TaqMan real time-PCR. RESULTS: Lactose malabsorption linked to the CC genotype did not associate with an increased risk for either colorectal cancer (OR=1.041; 95% CI=0.751-1.442; p=0.868) or polyps (OR=0.927; 95% CI=0.630-1.363; p=0.769). There was no association with colorectal cancer/polyps site. 60% of the subjects overall bore the CC genotype. CONCLUSION: In the Italian population the LCT-13910C>T polymorphism is not associated to the risk for colorectal cancer or polyps. PMID- 20362523 TI - Breast enhancement using MacrolaneTM: a report of complications in three patients and a review of this new product. AB - MacrolaneTM, an injectable compound composed of hyaluronic acid, has recently been marketed for breast enhancement. Three patients who presented to the authors with complications soon after treatment elsewhere are reported. One had severe infection and two had grade 3 capsular contracture. All three patients underwent a surgical procedure to treat their complication. The use of MacrolaneTM for breast enhancement is reviewed together with previously published data. PMID- 20362524 TI - Defensive approach to the hemisoleous flap for compound tibial fractures. PMID- 20362525 TI - Lipografted tenolysis. AB - We present a case where recurrent adherence of extensor tendons on the left foot of a 54-year-old woman was treated successfully with tenolysis supplemented by autologous fat transplant in the form of lipofilling. PMID- 20362526 TI - Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4 hydroxybutyl) nitrosamine-induced bladder cancer. AB - BACKGROUND: Green tea polyphenol (GTP) suppresses malignancy in bladder cancer cell lines. However, the detail of its anti-carcinogenic effect in vivo is not fully understood. This study investigated the effect of GTP on bladder tumor size and angiogenesis in mice given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN), with and without GTP. METHODS: Eight-week-old female C3H/He mice were treated with and without 0.05% BBN solution for 14 or 24 weeks. In addition, they were also treated with and without 0.5% GTP solution for the same periods. Histopathological diagnosis was established using hematoxylin and eosin staining, and microvessel density (MVD) was estimated by counting CD34- and von Willebrand factor-positive vessels in the tumor area. RESULTS: At 14 weeks, cancer cells were detected in BBN and BBN+GTP mice [5/14 (35.7%) and 3/14 (21.4%), respectively, p=0.678]. At 24 weeks, the incidence of cancer cells was also similar between the groups (BBN+GTP: 61.9% vs. BBN: 82.6%; p=0.179). However, the frequency of invasive tumors in BBN+GTP mice was significantly lower (23.8%; p=0.030) than in those given BBN alone (65.2%). Tumor volume and MVD of intratumoral and stromal region in the BBN+GTP group were also significantly lower than in BBN mice. CONCLUSION: The results showed that GTP had no anti carcinogenic effect, but inhibited tumor growth and invasion in mice with established bladder cancer, at least in part through the regulation of angiogenesis. Our data suggest that GTP seems to suppress tumor development in bladder cancer. PMID- 20362527 TI - Cell competition: pirates on the tangled bank. AB - Competition by stem cells for occupation of a limited niche is a well-described phenomenon. Two recent studies highlight competition between hematopoietic stem cells based on p53. These findings have implications for both normal homeostasis and tumorigenesis. PMID- 20362528 TI - Visualizing blood cell emergence from aortic endothelium. AB - Three recent Nature papers use time-lapse confocal imaging to visualize the birth of blood cells from the aortic endothelium. Two studies (Bertrand et al., 2010; Kissa and Herbomel, 2010) utilize the zebrafish embryo, while the third (Boisset et al., 2010) develops a novel technique to image the mouse aorta. PMID- 20362529 TI - Hooking up with Oct4. AB - The transcription factor Oct4 plays a central role in controlling the undifferentiated state of embryonic and induced pluripotent stem cells. Two complementary papers in this issue of Cell Stem Cell describe the extended network of proteins that interact with Oct4. Together, these studies broaden our understanding of the control of pluripotency. PMID- 20362530 TI - The hair follicle bulge stem cell niche resists transformation by the hedgehog pathway. AB - Similarities between basal cell carcinoma (BCC) tumor cells and hair follicle keratinocytes had previously suggested that BCC originates within the hair follicle bulge stem cell niche. However, in the current Nature Cell Biology, Youssef et al. (2010) show that BCC instead originates in the interfollicular epidermis. PMID- 20362531 TI - MicroRNA-9 controls a migratory mechanism in human neural progenitor cells. AB - MicroRNAs play roles in developmental switching; however, their roles in human neural progenitor cells (hNPCs) is poorly understood. In this issue of Cell Stem Cell, Delaloy et al. (2010) report that proliferation and migration choices in hNPCs are regulated by miR-9. PMID- 20362532 TI - Cycling toward elimination of leukemic stem cells. AB - In two recent articles in Science Translational Medicine and Nature Biotechnology, Saito et al. (2010) identify a molecular signature of acute myeloid leukemia (AML) stem cells and demonstrate that quiescent AML stem cells become sensitized to chemotherapy after G-CSF stimulation. PMID- 20362533 TI - "The immortal DNA strand": difficult to digest? PMID- 20362535 TI - Deconstructing pancreas development to reconstruct human islets from pluripotent stem cells. AB - There is considerable excitement about harnessing the potential of human stem cells to replace pancreatic islets that are destroyed in type 1 diabetes mellitus. However, our current understanding of the mechanisms underlying pancreas and islet ontogeny has come largely from the powerful genetic, developmental, and embryological approaches available in nonhuman organisms. Successful islet reconstruction from human pluripotent cells will require greater attention to "deconstructing" human pancreas and islet developmental biology and consistent application of conditional genetics, lineage tracing, and cell purification to stem cell biology. PMID- 20362536 TI - p53-mediated hematopoietic stem and progenitor cell competition. AB - Cell competition was originally described in Drosophila as a process for selection of the fittest cells. It is likely to play an important role in tissue homeostasis in all metazoans, but little is known about its role and regulation in mammals. By using genetic mosaic mouse models and bone marrow chimeras, we describe here a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell-autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells. PMID- 20362537 TI - MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell derived neural progenitors. AB - Human pluripotent stem cells offer promise for use in cell-based therapies for brain injury and diseases. However, their cellular behavior is poorly understood. Here we show that the expression of the brain-specific microRNA-9 (miR-9) is turned on in human neural progenitor cells (hNPCs) derived from human embryonic stem cells. Loss of miR-9 suppressed proliferation but promoted migration of hNPCs cultured in vitro. hNPCs without miR-9 activity also showed enhanced migration when transplanted into mouse embryonic brains or adult brains of a mouse model of stroke. These effects were not due to precocious differentiation of hNPCs. One of the key targets directly regulated by miR-9 encodes stathmin, which increases microtubule instability and whose expression in hNPCs correlates inversely with that of miR-9. Partial inhibition of stathmin activity suppressed the effects of miR-9 loss on proliferation and migration of human or embryonic rat neural progenitors. These results identify miR-9 as a novel regulator that coordinates the proliferation and migration of hNPCs. PMID- 20362538 TI - Efficient derivation of functional floor plate tissue from human embryonic stem cells. AB - The floor plate (FP) is a critical signaling center during neural development located along the ventral midline of the embryo. Little is known about human FP development because of the lack of tissue accessibility. Here we report the efficient derivation of human embryonic stem cell (hESC)-derived FP tissue capable of secreting Netrin-1 and SHH and patterning primary and hESC derived tissues. FP induction in hESCs is dependent on early SHH exposure and occurs at the expense of anterior neurectoderm (AN). Global gene expression and functional studies identify SHH-mediated inhibition of Dkk-1 as key factor in FP versus AN specification. hESC-derived FP tissue is shown to be of anterior SIX6+ character but is responsive to caudalizing factors suppressing SIX6 expression and inducing a shift in usage of region-specific SHH enhancers. These data define the early signals that drive human FP versus AN specification and determine regional identity in hESC-derived FP. PMID- 20362539 TI - HOW is required for stem cell maintenance in the Drosophila testis and for the onset of transit-amplifying divisions. AB - The mechanisms by which germline stem cells (GSCs) in the Drosophila testis undergo asymmetric division to regenerate a stem cell as well as a daughter (gonialblast) that will only undergo a further four mitotic divisions prior to entering premeiotic S phase and differentiating into a cyst of spermatocytes are not fully resolved. Here we demonstrate that the HOW RNA-binding protein is required for maintenance of CycB and therefore mitotic progression in GSCs and gonialblasts as well as determining the timing of the spermatogonial divisions. HOW is normally expressed in a complementary pattern to Bam in the germline and bam mRNA is bound by HOW in vivo. Ectopic expression of the HOW(L) isoform is associated with a delay in accumulation of Bam to the level required for differentiation, resulting in extra mitotic divisions. Spatiotemporal regulation of HOW expression is therefore required to specify the four spermatogonial transit-amplifying divisions. PMID- 20362540 TI - Distinguishing mast cell and granulocyte differentiation at the single-cell level. AB - The lineage restriction of prospectively isolated hematopoietic progenitors has been traditionally assessed by bulk in vitro culture and transplantation of large number of cells in vivo. These methods, however, cannot distinguish between homogenous multipotent or heterogeneous lineage-restricted populations. Using clonal assays of 1 or 5 cells in vitro, single-cell quantitative gene expression analyses, and transplantation of mice with low numbers of cells, we show that a common myeloid progenitor (CMP) is Sca-1(lo)lin(-)c-Kit(+)CD27(+)Flk-2(-) (SL CMP; Sca-1(lo) CMP) and a granulocyte/macrophage progenitor (GMP) is Sca 1(lo)lin(-)c-Kit(+)CD27(+)Flk-2(+)CD150(-/lo) (SL-GMP; Sca-1(lo) GMP). We found that mast cell progenitor potential is present in the SL-CMP fraction, but not in the more differentiated SL-GMP population, and is more closely related to megakaryocyte/erythrocyte specification. Our data provide criteria for the prospective isolation of SL-CMP and SL-GMP and support the conclusion that mast cells are specified during hematopoiesis earlier than and independently from granulocytes. PMID- 20362541 TI - An Oct4-centered protein interaction network in embryonic stem cells. AB - Transcription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity. Whereas the genomic locations of several pluripotency transcription factors have been reported, the spectrum of their interaction partners is underexplored. Here, we use an improved affinity protocol to purify Oct4-interacting proteins from mouse embryonic stem cells (ESCs). Subsequent purification of Oct4 partners Sall4, Tcfcp2l1, Dax1, and Esrrb resulted in an Oct4 interactome of 166 proteins, including transcription factors and chromatin-modifying complexes with documented roles in self-renewal, but also many factors not previously associated with the ESC network. We find that Esrrb associated with the basal transcription machinery and also detect interactions between transcription factors and components of the TGF-beta, Notch, and Wnt signaling pathways. Acute depletion of Oct4 reduced binding of Tcfcp2l1, Dax1, and Esrrb to several target genes. In conclusion, our purification protocol allowed us to bring greater definition to the circuitry controlling pluripotent cell identity. PMID- 20362542 TI - An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. AB - The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its partners should illuminate how the pluripotent state is established and regulated. Here, we identify a considerably expanded set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 associates with a varied set of proteins including regulators of gene expression and modulators of Oct4 function. Half of its partners are transcriptionally regulated by Oct4 itself or other stem cell transcription factors, whereas one third display a significant change in expression upon cell differentiation. The majority of Oct4-associated proteins studied to date show an early lethal phenotype when mutated. A fraction of the human orthologs is associated with inherited developmental disorders or causative of cancer. The Oct4 interactome provides a resource for dissecting mechanisms of Oct4 function, enlightening the basis of pluripotency and development, and identifying potential additional reprogramming factors. PMID- 20362543 TI - Fluorescent-labeled antibodies: Balancing functionality and degree of labeling. AB - A critical assumption in using labeled antibodies is that the conjugation reaction has no deleterious effects on antibody avidity. This study demonstrates that this assumption need not hold true and presents a methodology to quantitatively determine the degree of inactivation and/or changes in antibody antigen binding that can occur with conjugation. Fluorescein isothiocyanate (FITC) was conjugated to a mouse monoclonal antibody, Fc125, against hemagglutinin (HA) using varying fluorophore/protein (F:P) labeling ratios. Antibody binding, as a function of the F:P labeling ratio, was evaluated using a kinetic enzyme-linked immunosorbent assay (ELISA) and analyzed using global fitting. A two-parameter adjustment of the antibody concentration and the maximum rate was sufficient to describe the rate changes. The concentration parameter dominated the rate changes, consistent with the hypothesis that the coupling reaction inactivated an increasing fraction of the antibody population with a smaller change ( approximately 15% at the highest F:P ratio) in antibody-antigen binding. An optimal F:P ratio that minimized both inactivation and unlabeled antibody was calculated. This procedure can be used to prepare functional, labeled antibody reagents with defined activity and can aid in quantitative applications where the stoichiometry and functionality of the labeled antibody are critical. PMID- 20362544 TI - Mitochondrial carriers function as monomers. AB - Mitochondrial carriers link biochemical pathways in the mitochondrial matrix and cytosol by transporting metabolites, inorganic ions, nucleotides and cofactors across the mitochondrial inner membrane. Uncoupling proteins that dissipate the proton electrochemical gradient also belong to this protein family. For almost 35 years the general consensus has been that mitochondrial carriers are dimeric in structure and function. This view was based on data from inhibitor binding studies, small-angle neutron scattering, electron microscopy, differential tagging/affinity chromatography, size-exclusion chromatography, analytical ultracentrifugation, native gel electrophoresis, cross-linking experiments, tandem-fusions, negative dominance studies and mutagenesis. However, the structural folds of the ADP/ATP carriers were found to be monomeric, lacking obvious dimerisation interfaces. Subsequently, the yeast ADP/ATP carrier was demonstrated to function as a monomer. Here, we revisit the data that have been published in support of a dimeric state of mitochondrial carriers. Our analysis shows that when critical factors are taken into account, the monomer is the only plausible functional form of mitochondrial carriers. We propose a transport model based on the monomer, in which access to a single substrate binding site is controlled by two flanking salt bridge networks, explaining uniport and strict exchange of substrates. PMID- 20362545 TI - Investigation of the enzymatic activity of the Na+,K+-ATPase via isothermal titration microcalorimetry. AB - Isothermal titration microcalorimetry (ITC) is shown here to be a sensitive and accurate method for assaying the steady-state enzyme activity of the Na+,K+ ATPase. Single ATP injection experiments yield an apparent enthalpy change for the ATP hydrolysis reaction catalyzed by the enzyme of -51 (+/-1) kJ mol(-1). This value is independent of the amount of ADP accumulated in the sample cell, which indicates that under the experimental conditions studied here (saturating Na+ and K+ concentrations) ADP does not inhibit enzyme activity by reversal of the phosphorylation reaction and resynthesizing ATP. Multiple ATP injection titration experiments in which varying concentrations of ADP were initially included in the sample cell could be adequately explained by a Michaelis-Menten kinetic model incorporating noncompetitive inhibition. This suggests that ADP inhibits the enzyme by binding to more than one enzyme intermediate and inhibiting forward reactions of the enzyme. Values of Km and KI obtained for the fits agree with literature values obtained by other methods. Because ITC is a direct method of continually monitoring enzyme activity, it is a valuable supplement to less direct or noncontinuous methods such as colorimetric, enzyme coupled or radioactivity-based assays. PMID- 20362546 TI - Energetics in photosystem II from Thermosynechococcus elongatus with a D1 protein encoded by either the psbA1 or psbA3 gene. AB - The main cofactors involved in the function of Photosystem II (PSII) are borne by the D1 and D2 proteins. In some cyanobacteria, the D1 protein is encoded by different psbA genes. In Thermosynechococcus elongatus the amino acid sequence deduced from the psbA3 gene compared to that deduced from the psbA1 gene points a difference of 21 residues. In this work, PSII isolated from a wild type T. elongatus strain expressing PsbA1 or from a strain in which both the psbA1 and psbA2 genes have been deleted were studied by a range of spectroscopies in the absence or the presence of either a urea type herbicide, DCMU, or a phenolic type herbicide, bromoxynil. Spectro-electrochemical measurements show that the redox potential of PheoD1 is increased by 17 mV from -522 mV in PsbA1-PSII to -505 mV in PsbA3-PSII. This increase is about half that found upon the D1-Q130E single site directed mutagenesis in Synechocystis PCC 6803. This suggests that the effects of the D1-Q130E substitution are, at least partly, compensated for by some of the additional amino-acid changes associated with the PsbA3 for PsbA1 substitution. The thermoluminescence from the S2QA-* charge recombination and the C identical with N vibrational modes of bromoxynil detected in the non-heme iron FTIR difference spectra support two binding sites (or one site with two conformations) for bromoxynil in PsbA3-PSII instead of one in PsbA1-PSII which suggests differences in the QB pocket. The temperature dependences of the S2QA-* charge recombination show that the strength of the H-bond to PheoD1 is not the only functionally relevant difference between the PsbA3-PSII and PsbA1-PSII and that the environment of QA (and, as a consequence, its redox potential) is modified as well. The electron transfer rate between P680+* and YZ is found faster in PsbA3 than in PsbA1 which suggests that the redox potential of the P680/P680+* couple (and hence that of 1P680*/P680+*) is tuned as well when shifting from PsbA1 to PsbA3. In addition to D1-Q130E, the non-conservative amongst the 21 amino acid substitutions, D1-S270A and D1-S153A, are proposed to be involved in some of the observed changes. PMID- 20362547 TI - Enhancement of TREK1 channel surface expression by protein-protein interaction with beta-COP. AB - TREK1 belongs to a family of two-pore-domain K(+) (K(2P)) channels and produce background currents that regulate cell excitability. In the present study, we identified a vesicle transport protein, beta-COP, as an interacting partner by yeast two-hybrid screening of a human brain cDNA library with N-terminal region of TREK1 (TREK1-N) as bait. Several in vitro and in vivo binding assays confirmed the protein-protein interaction between TREK1 and beta-COP. We also found that beta-COP was associated with TREK1 in native condition at the PC3 cells. When RFP beta-COP was co-transfected with GFP-TREK1 into COS-7 cells, both proteins were found localized to the plasma membrane. In addition, the channel activity and surface expression of GFP-TREK1 increased dramatically by co-transfection with RFP-beta-COP. Surface expression of the TREK1 channel was also clearly reduced with the addition of beta-COP-specific shRNA. Collectively, these data suggest that beta-COP plays a critical role in the forward transport of TREK1 channel to the plasma membrane. PMID- 20362548 TI - Glucose-induced translocation of coronin 3 regulates the retrograde transport of the secretory membrane in the pancreatic beta-cells. AB - GTP-Rab27a is known to regulate insulin exocytosis. We have recently reported that coronin 3, which paradoxically binds GDP-Rab27a, participates in endocytosis of the insulin secretory membrane. Here, we demonstrate that glucose stimulation caused redistribution of coronin 3 in the vicinity of the plasma membrane, which was mimicked by overexpression of the GDP-Rab27a mutant or the Rab27a GAP. Glucose-induced translocation of coronin 3 was inhibited by Rab27a knock-down. The internalized phogrin, an insulin granule associated protein, located near the plasma membrane by the dominant-negative coronin 3, but the protein at the outer surface of the plasma membrane was decreased. These results indicate that glucose recruits coronin 3 near the plasma membrane, and that it regulates the retrograde transport of the secretory membrane in pancreatic beta-cells. PMID- 20362549 TI - Adhesion-mediated self-renewal abilities of Ph+ blastoma cells. AB - The Philadelphia chromosome-positive blastoma, maintained by serial subcutaneous transplantation in nude mice, is a highly proliferating biological mass consisting of homogenous CD34(+)CD38(-) myeloblastoid cells. These cells newly evolved from pluripotent leukemia stem cells of chronic myeloid leukemia in the chronic phase. Therefore, this mass may provide a unique tool for better understanding cellular and molecular mechanisms of self-renewal of leukemia stem cells. In this paper, we demonstrated that intravenously injected blastoma cells can cause Ph+ blastic leukemia with multiple invasive foci in NOD/SCID mice but not in nude mice. In addition, using an in vitro culture system, we clearly showed that blastoma cell adhesion to OP9 stromal cells accelerates blastoma cell proliferation that is associated with up-regulation of BMI1 gene expression; increased levels of beta-catenin and the Notch1 intra-cellular domain; and changed the expression pattern of variant CD44 forms, which are constitutively expressed in these blastoma cells. These findings strongly suggest that adhesion of leukemic stem cells to stromal cells via CD44 might be indispensable for their cellular defense against attack by immune cells and for maintenance of their self renewal ability. PMID- 20362550 TI - Maintained activity of glycogen synthase kinase-3beta despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model. AB - Glycogen synthase kinase-3beta (GSK3beta) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3beta. However, the inactive form of GSK3beta which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3beta substrates, such as beta-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase 2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly, OA also induces phosphorylation of GSK3beta at serine-9 and other substrates including tau, beta-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3beta inhibitors such as lithium chloride and 6-bromoindirubin 3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3beta may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A compromised conditions and that GSK3beta inhibitors could be a valuable drug candidate in AD. PMID- 20362551 TI - Characterization of the interaction of influenza virus NS1 with Akt. AB - Avian influenza viruses belong to the genus influenza A virus of the family Orthomyxoviridae. The influenza virus consists of eight segmented minus stranded RNA that encode 11 known proteins. Among the 11 viral proteins, NS1 (non structural protein 1, encoded on segment 8) has been implicated in the regulation of several important intra-cellular functions. In this report, we investigated the functional interaction of NS1 with serine threonine kinase Akt, a core intra cellular survival regulator. In co-immunoprecipitation assays and GST pull-down assays, NS1 directly interacted with Akt. The interaction was mediated primarily through the Akt-PH (Pleckstrin Homology) domain and the RNA-binding domain of NS1. NS1 preferentially interacted with phosphorylated Akt, but not with non phosphorylated Akt. Functionally, the NS1-Akt interaction enhanced Akt activity both in the intra-cellular context and in in vitro Akt kinase assays. Confocal microscopic analysis revealed that phosphorylated Akt interacted with NS1 during the interphase of the cell cycle predominantly within the nucleus. Finally, mass spectrometric analysis demonstrated the position at Thr215 of NS1 protein is primary phosphorylation target site through Akt activation. The results together supported the functional importance of influenza virus NS1 with Akt, a core intra cellular survival regulator. PMID- 20362552 TI - The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. AB - Asthma is a chronic inflammatory airway disease characterized by airway hyperreactivity, increased mucus production, and reversible airway contraction. Asthma is a complex genetic trait caused by environmental factors in genetically predisposed individuals. The transportation of maternal antigen-specific IgG via amniotic fluid, placenta and breast milk plays an important role in passive immunity. First, to examine whether maternal passive immunity by the transportation of antigen-specific IgG via FcRn regulates allergic airway inflammation, ovalbumin-immunized FcRn(+/-) female mice were bred with FcRn(-/-) male mice to evaluate the degree of ovalbumin-induced allergic airway inflammation of FcRn(-/-) offspring. Maternal passive immunity regulated allergic airway inflammation in an FcRn-dependent manner. Second, to examine the role of maternal antigen-specific IgG1 injection into mothers, we intravenously injected ovalbumin-specific IgG1 into wild-type or FcRn(+/-) mice immediately after they gave birth. The offspring were sensitized and challenged with ovalbumin. Antigen specific IgG1 administered to lactating mice reduced allergic airway inflammation in their offspring in an FcRn-dependent manner. Last, to exclude the factor of maternal passive immunity other than ovalbumin-specific IgG1, we administered ovalbumin-specific IgG1 orally to offspring after birth. Oral administration of ovalbumin-specific IgG1 to offspring during the lactating period prevented the development of allergic airway inflammation in an FcRn-dependent manner. These data show that the transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. PMID- 20362553 TI - Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: implications for cell proliferation control. AB - Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences. PMID- 20362554 TI - ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells. AB - Apoptosis signal-regulating kinase 1 (ASK1) and ASK2 are both members of mitogen activated protein kinase kinase kinase (MAP3K) family that are implicated in apoptotic cell death, stress responses, and various diseases. We have determined that NT2RI3007443, TESTI4031745, SGK341, and human MAP3K15 are all transcribed from the same genomic locus, which we designate "ASK3 gene" based on sequence homology to ASK1 and ASK2. NT2RI3007443, TESTI4031745, and SGK341 displayed distinct expression profiles among human tissues. TESTI4031745 was expressed in relatively high levels. The expression of TESTI4031745 was increased in rectum tumor and Alzheimer's disease hippocampus and decreased in kidney tumor and Alzheimer's disease frontal lobe. NT2RI3007443 showed moderate levels of ubiquitous expression in normal adult tissues. They did not drastically change in diseases except for increase in cirrhosis liver. Expression of SGK341 was restricted. It was highly expressed in fetal brain, and moderately expressed in normal hippocampus, pancreas, spleen, lung, and kidney. Further, its expression was dramatically increased in hepatic cirrhosis and decreased in lung tumor. Target proteins encoded by NT2RI3007443 and TESTI4031745 were translated in cell free protein synthesis system. They exhibited protein kinase activity indicated by ATP consumption and phosphorylation of Syntide 2 as a substrate. We demonstrated that knockdown of ASK3 protected HeLa cells against cytotoxicity induced by anti-Fas monoclonal antibody, TNF-alpha, or oxidative stress. These findings suggest that "ASK3 gene" is a novel member of apoptosis signal regulating kinases and that it plays a pivotal role in the signal transduction pathway implicated in apoptotic cell death triggered by cellular stresses. It can be a putative therapeutic drug target for multiple human diseases. PMID- 20362555 TI - Diverse FGF receptor signaling controls astrocyte specification and proliferation. AB - During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS. PMID- 20362556 TI - Overexpressed ATP7B protects mesenchymal stem cells from toxic copper. AB - Wilson's disease (WD) is characterized by accumulation of high levels of copper in liver due to malfunction of copper transporter ATP7B which is central for copper homeostasis. Here we report for the first time that mesenchymal stem cells (MSC) derived from bone marrow express detectable levels of ATP7B. The role of ATP7B overexpression for MSC survival and selection in high copper was investigated. Hepatoma cell line HepG2 that has a high intrinsic expression of ATP7B served as a control. Using retroviral vector a significant higher expression level of ATP7B could be achieved in MSCs. Whereas copper treatment resulted in cell death in untransduced MSCs, viability assays demonstrated a unique copper resistance of ATP7B overexpressing MSCs that outcompeted HepG2. In long-term cell culture stable transgene expression for up to 9weeks was shown for ATP7B overexpressing MSCs which rapidly overgrew untransduced cells. Our findings suggest that ATP7B overexpression provides an important selection advantage to MSCs in high copper microenvironments, and may represent novel cell transplants for therapy of WD. PMID- 20362557 TI - Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma. AB - Syrbactins belong to a new class of proteasome inhibitors which include syringolins and glidobactins. These small molecules are structurally distinct from other, well-established proteasome inhibitors, and bind the eukaryotic 20S proteasome by a novel mechanism. In this study, we examined the effects of syringolin A (SylA) and glidobactin A (GlbA) as well as two synthetic SylA analogs (SylA-PEG and SylA-LIP) in human neuroblastoma (SK-N-SH), human multiple myeloma (MM1.S, MM1.RL, and U266), and human ovarian cancer (SKOV-3) cells. While all four syrbactins inhibited cell proliferation in a dose-dependent manner, GlbA was most potent in both dexamethasone-sensitive MM1.S cells (IC(50): 0.004microM) and dexamethasone-resistant MM1.RL cells (IC(50): 0.005microM). Syrbactins also inhibited the chymotrypsin-like proteasome activity in a dose-dependent fashion, and GlbA was most effective in SK-N-SH cells (IC(50): 0.015microM). The GlbA promoted inhibition of proteasomal activity in SK-N-SH cells resulted in the accumulation of ubiquitinated proteins and tumor suppressor protein p53 and led to apoptotic cell death in a time-dependent manner. GlbA treatment also promoted the activation of Akt/PKB via phosphorylation at residue Ser(473) and induced autophagy as judged by the presence of the lipidated form of microtubule associated protein 1 light chain 3 (LC3) and autophagosomes. Collectively, our data suggest that syrbactins belong to a new and effective proteasome inhibitor class which promotes cell death. Proteasome inhibition is a promising strategy for targeted anticancer therapy and syrbactins are a new class of inhibitors which provide a structural platform for the development of novel, proteasome inhibitor-based drug therapeutics. PMID- 20362558 TI - Differential expression and alternative splicing of genes in lumbar spinal cord of an amyotrophic lateral sclerosis mouse model. AB - Amyotrophic lateral sclerosis (ALS) is one of the most common adult-onset neurodegenerative diseases, with progressive paralysis and muscle atrophy. The exact pathogenic mechanism remains unknown, but recent evidence suggests that differential gene expression and gene splicing may play a significant role. We used Affymetrix GeneChip Mouse Exon 1.0 ST Array to investigate the expression profiling of lumbar spinal cord samples from SOD1-G93A transgenic mice, the widely used animal model of ALS. The de-regulated genes analyzed either from the expression level or from the alternative splicing level both showed overlapping GO categories and pathway mapping. Our findings indicate that cell adhesion, immune-inflammation response and lipid metabolism all play important roles in the onset of ALS. Detailed analysis by RT-PCR of key genes confirmed the experimental results of microarrays. These results suggest a multi-factor mechanism in ALS development. PMID- 20362559 TI - Protein levels of heat shock proteins 27, 32, 60, 70, 90 and thioredoxin-1 in amnestic mild cognitive impairment: an investigation on the role of cellular stress response in the progression of Alzheimer disease. AB - Heat shock proteins (HSPs) are highly regulated proteins that are involved in normal cellular activity and are up-regulated when the cell is exposed to stress such as heat or excess reactive oxygen species (ROS) production. HSPs are molecular chaperones that mediate the proper folding of proteins and promote recovery of the native conformations of proteins lost due to stress. Improperly folded or denatured proteins tend to aggregate and accumulate in cells. A number of neurodegenerative diseases such as Parkinson disease (PD) and Alzheimer disease (AD) have been called "protein misfolding disorders" due their characteristic pathology. Until now the exact mechanism(s) of AD progression and pathogenesis largely remains unknown. Reasoning that stress is present in brain in AD, we tested the suggestion that HSP levels would be increased in amnestic mild cognitive impairment (aMCI), a transition stage between normal aging and AD. Accordingly, in the present study we measured the levels of HSPs in hippocampus, inferior parietal lobule (IPL) and cerebellum of subjects with aMCI. The results show a general induction of HSPs and decreased levels of Thioredoxin 1 in aMCI brain suggesting that alteration in the chaperone protein systems might contribute to the pathogenesis and progression of AD. The results also are consistent with the notion that targeting HSP could be a therapeutic approach to delay the progression of aMCI to AD. PMID- 20362560 TI - Decreased dopamine type 2 receptor availability after bariatric surgery: preliminary findings. AB - BACKGROUND: Diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms. We hypothesized that dopaminergic neurotransmission would be enhanced after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery. METHODS: Five females with obesity were studied preoperatively and at approximately 7 weeks after RYGB or VSG surgery. Subjects underwent positron emission tomography (PET) imaging with a dopamine type 2 (DA D2) receptor radioligand whose binding is sensitive to competition with endogenous dopamine. Regions of interest (ROI) relevant to eating behaviors were delineated. Fasting enteroendocrine hormones were quantified at each time point. RESULTS: Body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean+/-SEM) were caudate 10+/-3%, putamen 9+/-4%, ventral striatum 8+/ 4%, hypothalamus 9+/-3%, substantia nigra 10+/-2%, medial thalamus 8+/-2%, and amygdala 9+/-3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%). CONCLUSION: The decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures. PMID- 20362561 TI - Involvement of the spinal NMDA receptor/PKCgamma signaling pathway in the development of bone cancer pain. AB - N-methyl-d-aspartate (NMDA) receptor and protein kinase C (PKC) play important roles in the induction and maintenance of central sensitization during pain states. It has been shown that spinal NMDA receptor-dependent activation of PKCgamma facilitates nociception during neuropathic and inflammatory pain, but its involvement in bone cancer pain has not previously been established. The aim of this study was to examine the potential role of the spinal NMDA receptor/PKCgamma signaling pathway in the development of bone cancer pain. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer-related pain behaviors. At day 7, 10 and 14 after operation, the expression of PKCgamma mRNA in the spinal cord was higher in tumor-bearing mice compared to the sham mice. At day 14, intrathecal administration of 5 microg of NR2B subunit-specific NMDA receptor antagonist ifenprodil attenuated the up-regulation of PKCgamma mRNA in the spinal cord as well as bone cancer-evoked thermal hyperalgesia and mechanical allodynia. Furthermore, intrathecal injection of 10 microg of PKC inhibitor H-7 attenuated cancer-evoked thermal hyperalgesia and mechanical allodynia at day 14. These results suggest that the NMDA receptor/PKCgamma signaling pathway may participate in the development of bone cancer pain, and ifenprodil may be a useful alternative or adjunct therapy for bone cancer pain. PMID- 20362562 TI - Spectroscopic and thermodynamic evidence for antimicrobial peptide membrane selectivity. AB - In our laboratory we developed a series of antimicrobial peptides that exhibit selectivity and potency for prokaryotic over eukaryotic cells (Hicks et al., 2007). Circular dichroism (CD), isothermal calorimetry (ITC) and calcein leakage assays were conducted to determine the mechanism of lipid binding of a representative peptide 1 (Ac-GF-Tic-Oic-GK-Tic-Oic-GF-Tic-Oic-GK-Tic-KKKK CONH(2)) to model membranes. POPC liposomes were used as a simple model for eukaryotic membranes and 4:1 POPC:POPG liposomes were used as a simple model for prokaryotic membranes. CD, ITC and calcein leakage data clearly indicate that compound 1 interacts via very different mechanisms with the two different liposome membranes. Compound 1 exhibits weaker binding and induces less calcein leakage in POPC liposomes than POPC:POPG (4:1 mole ratio) liposomes. The predominant binding mechanism to POPC appears to be limited to surface interactions while the mechanism of binding to 4:1 POPC:POPG most likely involves some type of pore formation. PMID- 20362563 TI - A FTO variant and risk of acute coronary syndrome. AB - BACKGROUND: The FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-case mortality. METHODS: We have analyzed the FTO rs17817449 variant in consecutive 1092 male patients with acute coronary syndrome (ACS) and in 1191 randomly selected Caucasian individuals (population controls). RESULTS: The FTO variant was significantly associated with BMI both in controls (P<0.02) and ACS patients (P<0.01). In both groups, BMI was highest in GG homozygotes and lowest in TT homozygotes. There was a significant difference between the ACS patients and controls in the frequency of the FTO genotype GG (21.4% vs. 15.9%, P<0.005). FTO GG homozygotes had a significantly increased risk of ACS, compared with TT homozygotes which was independent of age and BMI (odds ratio 1.49, 95% confidence interval 1.16-1.93). The odds ratio of ACS patients for the GG genotype remained significant even after the exclusion of diabetics (100 controls and 339 ACS patients), with OR 1.32 (95% CI 1.01-1.72). CONCLUSIONS: This study provides an evidence of an association between the FTO variant and risk of ACS in Caucasian males. PMID- 20362564 TI - A world apart: Inaccuracies of laboratory methodologies in antidoping testing. AB - Antidoping testing is currently exclusively based on haematochemical analysis performed in specialized laboratories accredited by WADA (World Anti-Doping Agency). Many of the analytical methods used for the determination of the parameters considered, such as haematological parameters (haemoglobin, haematocrit and reticulocytes), proteins (soluble transferrin receptor and hepcidin) and hormones (erythropoietin and growth hormone) are often affected by lack of clear standardization and harmonization. The observed incongruity of the data deriving from different laboratories often results in the risk of false positive results in athletes. This review wants to provide additional proofs in support of the need to improve the antidoping methodology involving different research and clinical institutions and skills. PMID- 20362565 TI - Discordant alpha-1 antitrypsin phenotype and genotype results in a liver transplant patient. PMID- 20362566 TI - Plasma homocysteine--a marker of vascular disease in elderly patients with mental illness. AB - BACKGROUND: Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentration than patients without vascular disease. METHOD: We investigated the influence of cobalamin/folate status and renal function on the association between plasma tHcy levels and vascular disease. RESULTS: There was a similar degree of significant difference in plasma tHcy levels between patients with and without vascular disease in all enrolled patients and in a group of patients where all those with signs of cobalamin/folate deficiency and/or impaired renal function had been excluded. Furthermore, logistic regression analysis showed that the age-adjusted plasma tHcy was the main predictor of vascular disease in both groups of patients. CONCLUSION: The findings suggest that the presence of vascular disease itself is associated with elevated levels of plasma tHcy. Plasma tHcy might be a marker of vascular disease in elderly patients with mental illness. PMID- 20362567 TI - Serum levels of basic fibroblastic growth factor (bFGF) in children with vascular anomalies: Another insight into endothelial growth. AB - OBJECTIVES: Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of the study was to determine the peripheral and local serum levels of bFGF in patients with hemangiomas and vascular malformations (VM). DESIGN AND METHODS: The study group consisted of 52 children with infantile hemangioma, 14 with VM and 36 healthy patients. bFGF serum levels were analyzed by an ELISA assay. Urinary bFGF was determined in 11 individuals with hemangioma. RESULTS: The serum peripheral bFGF concentrations in children with proliferating hemangiomas were lower than in healthy controls (p=0,03). There was no correlation between the measured cytokine level and hemangioma size, as well as patients' age. The serum local bFGF levels in 29 children with hemangiomas were higher than in the peripheral blood (p=0.022). Urinary bFGF in hemangioma patients did not differ statistically from healthy controls. CONCLUSIONS: (1) Determination of bFGF serum levels is not helpful in differentiating the phases of hemangioma growth and distinguishing hemangiomas from VM; (2) serum levels of bFGF cannot distinguish between extrinsic and intrinsic theories of endothelial cell proliferation in hemangiomas. PMID- 20362568 TI - Modulated function of tissue efflux transporters under hyperbilirubinemia in rats. AB - The effect of hyperbilirubinemia on the function of tissue efflux transporters such as multidrug resistance-associated proteins (Mrps) and organic anion transporting polypeptides (Oatps) was examined by measuring tissue accumulation of 2,4-dinitrophenyl-S-glutathione (DNP-SG) after intravenous administration of 1 chloro-2,4-dinitrobenzene (CDNB), a precursor of DNP-SG, in rats. DNP-SG is known as a substrate of both Mrps and Oatps. Hyperbilirubinemia was induced by a bolus intravenous administration of bilirubin. Treatment with probenecid, an inhibitor for both Mrps and Oatps, significantly increased DNP-SG concentrations in the brain, heart, liver, kidney, jejunum, spleen and skeletal muscle as compared with those in control rats, suggesting the expression of some probenecid-sensitive efflux transporters in these tissues. Rats with more than 70 microM of unconjugated/conjugated bilirubin in plasma exhibited significantly higher DNP-SG concentrations in the brain, liver, jejunum, and skeletal muscle. These results suggested that probenecid-sensitive efflux transporters in tissues were suppressed functionally under hyperbilirubinemia. In conclusion, hyperbilirubinemia accompanied by obstructive jaundice is caused by various disease states, which may increase harmful toxicities of exogenously administered Mrps and/or Oatps substrate drugs at various tissues, by suppressing the efflux transporter's function systemically. PMID- 20362569 TI - Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus. AB - This study is to investigate the effects of osthole on cognitive impairment and neuronal degeneration in hippocampus induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Permanent occlusion of bilateral common carotid arteries (2VO) induced severe cognitive deficits tested by the water maze task, along with oxidative stress and neuronal loss in hippocampus. Oral administration of osthole for 3 weeks markedly attenuated cognitive deficits and neuronal damage. Biochemical experiments revealed that osthole decreased the production of malondialdehyde (MDA) and significantly increased the activities of Glutathione Peroxidase (GPx) and Catalase. Western blot analyses indicated that osthole prevented the downregulation of bcl-2 expression and upregulation of bax expression, which resulted in decreasing bax/bcl-2 ratio in hippocampus of 2VO rats. Additionally, osthole effectively alleviated the activation of caspase-3 induced by permanent occlusion of bilateral common carotid arteries. The observed results in present study suggest that osthole exhibits therapeutic potential for vascular dementia, which is most likely related, at least in part, to its antioxidation and anti-apoptotic actions. PMID- 20362570 TI - Heterologous regulation of anion transporters by menthol in human airway epithelial cells. AB - The present study concerns previously unreported effects of menthol, a cyclic terpene alcohol produced by the peppermint herb, on anion transporters in polarized human airway Calu-3 epithelia. Application of menthol (0.01-1mM) attenuated transepithelial anion transport, estimated as short-circuit currents (I(SC)), after stimulation by forskolin (10microM) but not before. In contrast, menthol potentiated forskolin-stimulated and -unstimulated apical Cl(-) conductance, which reflected the cystic fibrosis transmembrane conductance regulator (CFTR: the cAMP-regulated Cl(-) channel)-mediated conductance, without correlation to changes in cytosolic cAMP levels. These results indicate that menthol-induced attenuation of forskolin-induced I(SC) despite CFTR up-regulation was due to cAMP-independent inhibition of basolateral anion uptake, which is the rate-limiting step for transepithelial anion transport. Analyses of the responsible basolateral anion transporters revealed that forskolin increased both bumetanide (an inhibitor of the basolateral Na(+)-K(+)-2Cl(-) cotransporter [NKCC1])- and DNDS (an inhibitor of basolateral HCO(3)(-)-dependent anion transporters [NBC1/AE2])-sensitive I(SC) in the control whereas only the former was prevented by the application of menthol. Neither the bumetanide- nor DNDS sensitive component was, however, reduced by menthol without forskolin. These heterologous effects of menthol were reproduced by latrunculin B, an inhibitor of actin polymerization. F-actin staining showed that menthol prevented forskolin stimulated rearrangements of actin microfilaments without affecting the distribution of forskolin-unstimulated microfilaments. Collectively, menthol functions as an activator of CFTR and prevents activation of NKCC1 without affecting NBC1/AE although all of these transporters are commonly cAMP-dependent. The heterologous effects may be mediated by the actin cytoskeleton, which interacts with CFTR and NKCC1. PMID- 20362571 TI - Influenza virus infection in multinucleated skeletal myofibers. AB - We examined the progression of the WSN influenza virus infection in isolated, multinucleated rat skeletal myofibers. Contrary to mononucleated cells, the adsorbed virions showed markedly delayed entry kinetics. Viral budding occurred on the sarcolemma, but the hemagglutinin envelope glycoprotein matured inefficiently and was poorly cleaved. Compatible with this, plaque assays indicated that infective viral particles were not formed. In situ hybridization studies showed that at low-dose infection, viral RNA production was restricted to one or a few nuclei within a myofiber. Dual in situ hybridization indicated that two different viral RNAs usually co-localized in the same nucleus or nuclei, suggesting that different viral genome segments replicated in the same nucleus. Newly synthesized viral ribonucleoprotein particles (vRNPs) did not re-enter virgin nuclei. Therefore, a single infected nucleus was able to support viral protein production, and notably, these proteins could reach hundreds of micrometers from the nucleus of origin. These results suggest that after viral disassembly in the endosome, the genome segments remained glued together and entered a myonucleus as a package. Spreading of the infection into virgin nuclei either by vRNPs or newly made virions did not occur, and thus the infection was abortive. PMID- 20362572 TI - Complex I: inhibitors, inhibition and neurodegeneration. AB - Complex I is the first protein component of the mitochondrial respiratory chain and as such plays a crucial role in ATP production and mitochondrial function in general. Mitochondrial dysfunction has been identified in a number of neurodegenerative diseases. In some of these the mitochondrial abnormality is primary and in others secondary. Mitochondrial toxins are capable of producing relatively selective neuronal cell death and have been used to produce models of human neurodegenerative diseases e.g. 1-methyl 4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) for Parkinson's disease, and 3-nitropropionic acid for Huntington's disease. Annonacin, an ingredient of local soursop, is a Complex I inhibitor and has been incriminated as the cause of a parkinsonian tauopathy disorder in Guadeloupe. A systematic analysis has identified several environmentally available potent lipophilic Complex I inhibitors that can induce neuronal cell death in striatal cultures and somatodendritic redistribution of tau protein. It is possible that these compounds may contribute to the pathogenesis of neurodegenerative disorders, although further work must be done to confirm their potential participation in pathogenesis. PMID- 20362573 TI - Long-term gonadal hormone treatment and endogenous neurogenesis in the dentate gyrus of the adult female monkey. AB - Neurogenesis occurs continually throughout life in all mammals and the extent of neurogenesis is influenced by many factors including gonadal hormones. Most research regarding hormones and neurogenesis has been performed on non-primate species. To determine whether gonadal hormones can modulate endogenous neurogenesis in the dentate gyrus (DG) of the hippocampus in non-human primates, ovariectomized (OVX) female rhesus monkeys received continuous, unopposed beta estradiol (OVX-E-Con), cyclic unopposed beta-estradiol (OVX-E-Cyc), continuous beta-estradiol+cyclic progesterone (OVX-E-Con+P-Cyc), or control (OVX-Veh) treatments. At week 29, all monkeys received BrdU injections for 4 consecutive days, in addition to the ongoing treatment. Twenty days after the last BrdU injection, all animals were sacrificed for tissue collection. In DG of hippocampus, scattered BrdU-ir cells were observed mainly in the subgranular zone (SGZ) and in the granule cell layer and occasionally these BrdU-ir cells in the SGZ formed clusters containing between 2 and 5 cells. In the granule cell layer and SGZ, virtually none of the BrdU-ir cells were either Dcx, a marker of immature neurons, or GFAP positive. However, an occasional BrdU-ir cell was positive for both neuronal marker NeuN or beta III-tubulin. Unbiased stereological analysis of BrdU-ir cells within the SGZ and the granule cell layer of DG revealed that among the experimental groups, there was no significant difference in number of BrdU-ir cells within the SGZ and the granule cell layer of the DG: OVX-E-Con (1801+/-218.7), OVX-E-Cyc (1783+/-415.6), OVX-E-Con+/-P-Cyc (1721+/-229.6), and OVX-Veh (1263+/-106.3), but a trend towards increased BrdU-ir cells was observed in all the experimental groups. PMID- 20362575 TI - FEBS Letters. Focus on... Lipid droplets. Introduction. PMID- 20362574 TI - The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats. AB - Immunophilin ligands, including cyclosporin-A (CsA), have been shown to be neuroprotective in experimental models of traumatic brain injury (TBI) and to attenuate the severity of traumatic axonal injury. Prior studies have documented CsA treatment to reduce essential components of posttraumatic axonal pathology, including impaired axoplasmic transport, spectrin proteolysis, and axonal swelling. However, the effects of CsA administration on axonal function, following TBI, have not been evaluated. The present study assessed the effects of CsA treatment on compound action potentials (CAPs) evoked in corpus callosum of adult rats following midline fluid percussion injury. Rats received a 20 mg/kg bolus of CsA, or cremaphor vehicle, at either 15 min or 1 h postinjury, and at 24 h postinjury CAP recording was conducted in coronal brain slices. To elucidate how injury and CsA treatments affect specific populations of axons, CAP waveforms generated largely by myelinated axons (N1) were analyzed separately from the CAP signal, which predominantly reflects activity in unmyelinated axons (N2). CsA administration at 15 min postinjury resulted in significant protection of CAP area, and this effect was more pronounced in N1, than in the N2, CAP component. This treatment also significantly protected against TBI-induced reductions in high-frequency responding of the N1 CAP signal. In contrast, CsA treatment at 1 h did not significantly protect CAPs but was associated with atypical waveforms in N1 CAPs, including decreased CAP duration and reduced refractoriness. The present findings also support growing evidence that myelinated and unmyelinated axons respond differentially to injury and neuroprotective compounds. PMID- 20362576 TI - The effect of pregnant and oestrous females on male testosterone and behaviour in the tammar wallaby. AB - Tammar wallaby females (Macropus eugenii) are seasonally breeding marsupials with a post-partum oestrus after a highly synchronised birth period when testosterone concentrations rise in males. Chemical communication appears to be important for mating, as males show checking behaviour, sniffing the urogenital opening (UGO) and the pouch of females. This study investigates whether the presence of pregnant and oestrous females directly influences testosterone in males and if oestrous odours or secretion from the pouch or UGO are attractive. Concentrations of plasma testosterone were measured in males housed with pregnant and oestrous females during two consecutive cycles in the breeding season, and an artificially induced cycle in the non-breeding season. Males were also tested for their interest in swabs taken from the urogenital opening (UGO) or pouch of oestrous females. Testosterone increased sharply in males in the presence of pregnant and oestrous females during all cycles in both seasons, but there was no change when males were exposed to non-cycling females in lactational or seasonal diapause. Males had no preference for either oestrous or non-oestrous samples taken from the pouch or from the UGO from oestrous females. This study confirms that the increase in plasma testosterone in tammar males can be induced through the presence of pregnant and oestrous females, regardless of season and that the increase began when the females were in late-pregnancy. This confirms that the male's reproductive state is dependent on a signal from females and is not blocked through seasonal effects. PMID- 20362577 TI - Paternal behavior increases testosterone levels in offspring of the California mouse. AB - Paternal care during early development influences pup survivorship in the monogamous and biparental California mouse, Peromyscus californicus. Moreover, paternal pup retrievals impact development of adult offspring aggression and the neuropeptide vasopressin, yet little is known about the underlying mechanisms of these developmental changes. Because testosterone can increase arginine vasopressin and aggression, we hypothesized that paternal pup retrievals increase testosterone levels in prepubertal male P. californicus pups. Male pups were assigned to one of three groups: hormonal baseline, nonretrieval control, or retrieval. On postnatal days 18-21, all pups and the mother were removed from the cage, and the focal male pup was placed either outside of the nest to elicit paternal retrievals (retrieval group) or in the nest to discourage paternal retrievals (nonretrieval group). Testosterone was elevated at 45-min, but not 90 min, post-manipulation in retrieved compared to nonretrieved pups. Moreover, there was a significant positive correlation between pup retrievals and testosterone in the 45-min group. This rapid testosterone rise in response to paternal retrievals may facilitate an increase in aggression and vasopressin in adult offspring. Therefore, this period of development previously viewed as hormonally quiescent may be more active in response to paternal behavior than previously thought. PMID- 20362578 TI - Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch. AB - Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. PMID- 20362579 TI - Perinatal exposure to progesterone, estradiol, or mifepristone affects sexual differentiation of behavior in opossums (Monodelphis domestica). AB - The effects of perinatal exposure to progesterone (P) and estradiol (E) on sexual differentiation of behavior and morphology were examined by treating male and female gray short-tailed opossums on postnatal day 8 with progesterone alone (P), P plus estradiol (E) (PE), the P receptor antagonist mifepristone/RU486 (MIF), or corn oil control (C) and gonadectomizing them before puberty. When given female hormone replacement therapy in adulthood and tested with intact stimulus males, MIF animals showed less female-typical aggressive threat behavior than animals in other treatment groups. Stimulus males scent marked in more tests involving females than males and in more tests involving MIF animals than animals in other treatment groups. Body weight was lower in females than in males and was lower in MIF animals than in animals in other treatment groups, and P females failed to show female-typical genital locks after copulation. Sexual receptivity was similar in males and females and, while not decreased by any perinatal hormone treatment, was higher in PE males than in animals of either sex in any treatment group. These findings suggest that perinatal exposure to P is associated with the organization of feminine threat behavior and the defeminization of attractivity, body weight and genital anatomy in this marsupial. Reasons for these findings and for why female sexual receptivity is enhanced by perinatal exposure to exogenous E only in an endogenous masculine environment are discussed. PMID- 20362581 TI - Mitochondrial genes for heme-dependent respiratory chain complexes are up regulated after depletion of Wolbachia from filarial nematodes. AB - The filarial nematodes Brugia malayi, Wuchereria bancrofti and Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at risk population. To identify new targets for anti wolbachial therapy, understanding the molecular basis of the Wolbachia-filaria symbiosis is required. Using the B. malayi microarray we identified differentially expressed genes in the rodent filaria Litomosoides sigmodontis after depletion of Wolbachia which might have a role in symbiosis. The microarray data were filtered for regulated genes with a false discovery rate <5% and a > or = 2-fold-change. Most of the genes were differentially expressed at day 36 of tetracycline treatment, when 99.8% of Wolbachia were depleted. Several classes of genes were affected, including genes for translation, transcription, folding/sorting of proteins, motility, structure and metabolic and signalling pathways. Quantitative PCR validated 60% of the genes found to be regulated in the microarray. A nuclear encoded heme-binding protein of the globin family was up-regulated upon loss of Wolbachia. Interestingly, mitochondrial encoded subunits of respiratory chain complexes containing heme and riboflavin were also up-regulated. No change in the expression of these genes was seen in tetracycline treated Wolbachia-free Acanthocheilonema viteae. As Wolbachia synthesise heme and filaria do not, we hypothesise that without the endosymbionts no functional heme containing enzymes can be formed, leading to loss of energy metabolism which then results in up-regulation of the mitochondrial encoded subunits in an attempt to correct the deviation from homeostasis. Our results support targeting the Wolbachia heme synthesis pathway for the discovery of new anti-filarial drugs. PMID- 20362580 TI - Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats. AB - Although previous research has indicated that hormone replacement therapy benefits memory in menopausal women, several recent studies have shown either detrimental or no effects of treatment. These inconsistencies emphasize the need to evaluate the role of ovarian hormones in protecting against age-related cognitive decline in an animal model. The present study investigated the effects of long-term hormone treatment during aging on the Morris water maze. Female Long Evans hooded rats were ovariectomized at middle age (12-13 months) and were immediately placed in one of five groups: no replacement, chronic 17 beta estradiol only, chronic 17 beta-estradiol and progesterone, chronic 17 beta estradiol and medroxyprogesterone acetate (MPA), or cyclic 17 beta-estradiol only. 17 beta-estradiol was administered in the drinking water in either a chronic or cyclic (3 out of 4 days) fashion. Progesterone and MPA were administered via subcutaneous pellets. Following 6 months of hormone treatment, animals were tested on the Morris water maze. Animals performed four trials a day for 4 days and after the final day of testing a subset of animals completed a probe trial. Across 4 days of testing, rats receiving 17 beta-estradiol in combination with MPA performed significantly worse than all other groups receiving hormone replacement. In addition on the last day of testing, chronic 17 beta-estradiol administration was more beneficial than cyclic administration and no replacement. Thus compared to other hormone-treated groups, long-term 17 beta estradiol treatment in combination with MPA results in impaired performance on the spatial Morris water maze. PMID- 20362582 TI - Baculovirus infection influences host protein expression in two established insect cell lines. AB - We identified host proteins that changed in response to host cell susceptibility to baculovirus infection. We used three baculovirus-host cell systems utilizing two cell lines derived from pupal ovaries, Hz-AM1 (from Helicoverpa zea) and Hv AM1 (from Heliothis virescens). Hv-AM1 cells are permissive to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and semi-permissive to H. zea single nucleopolyhedrovirus (HzSNPV). Hz-AM1 cells are non-permissive to AcMNPV. We challenged each cell line with baculovirus infection and after 24h determined protein identities by MALDI TOF/TOF mass spectrometry. For Hv-AM1 cells, 21 proteins were identified, and for Hz-AM1 cells, 19 proteins were newly identified (with 8 others having been previously identified). In the permissive relationship, 18 of the proteins changed in expression by 70% or more in AcMNPV infected Hv-AM1 cells as compared with non-infected controls; 12 were significantly decreased and 6 cellular proteins were significantly increased. We also identified 3 virus-specific proteins. In the semi-permissive infections, eight proteins decreased by 2-fold or more. Non-permissive interactions did not lead to substantial changes in host cell protein expression. We hypothesize that some of these proteins act in determining host cell specificity for baculoviruses. PMID- 20362583 TI - Aldehyde dehydrogenase 2 knockout accentuates ethanol-induced cardiac depression: role of protein phosphatases. AB - Alcohol consumption leads to myocardial contractile dysfunction possibly due to the toxicity of ethanol and its major metabolite acetaldehyde. This study was designed to examine the influence of mitochondrial aldehyde dehydrogenase-2 (ALDH2) knockout (KO) on acute ethanol exposure-induced cardiomyocyte dysfunction. Wild-type (WT) and ALDH2 KO mice were subjected to acute ethanol (3g/kg, i.p.) challenge and cardiomyocyte contractile function was assessed 24h later using an IonOptix edge detection system. Western blot analysis was performed to evaluate ALDH2, protein phosphatase 2A (PP2A), phosphorylation of Akt, and glycogen synthase kinase-3beta (GSK-3beta). ALDH2 KO accentuated ethanol induced elevation in cardiac acetaldehyde levels. Ethanol exposure depressed cardiomyocyte contractile function including decreased cell shortening amplitude and maximal velocity of shortening/relengthening as well as prolonged relengthening duration and a greater decline in peak shortening in response to increasing stimulus frequency, the effect of which was significantly exaggerated by ALDH2 KO. ALDH2 KO also unmasked an ethanol-induced prolongation of shortening duration. In addition, short-term in vitro incubation of ethanol-induced cardiomyocyte mechanical defects was exacerbated by the ALDH inhibitor cyanamide. Ethanol treatment dampened phosphorylation of Akt and GSK-3beta associated with upregulated PP2A, which was accentuated by ALDH2 KO. ALDH2 KO aggravated ethanol induced decrease in mitochondrial membrane potential. These results suggested that ALDH2 deficiency led to worsened ethanol-induced cardiomyocyte function, possibly due to upregulated expression of protein phosphatase, depressed Akt activation, and subsequently impaired mitochondrial function. These findings depict a critical role of ALDH2 in the pathogenesis of alcoholic cardiomyopathy. PMID- 20362584 TI - Mutating the converter-relay interface of Drosophila myosin perturbs ATPase activity, actin motility, myofibril stability and flight ability. AB - We used an integrative approach to probe the significance of the interaction between the relay loop and converter domain of the myosin molecular motor from Drosophila melanogaster indirect flight muscle. During the myosin mechanochemical cycle, ATP-induced twisting of the relay loop is hypothesized to reposition the converter, resulting in cocking of the contiguous lever arm into the pre-power stroke configuration. The subsequent movement of the lever arm through its power stroke generates muscle contraction by causing myosin heads to pull on actin filaments. We generated a transgenic line expressing myosin with a mutation in the converter domain (R759E) at a site of relay loop interaction. Molecular modeling suggests that the interface between the relay loop and converter domain of R759E myosin would be significantly disrupted during the mechanochemical cycle. The mutation depressed calcium as well as basal and actin-activated MgATPase (V(max)) by approximately 60% compared to wild-type myosin, but there is no change in apparent actin affinity (K(m)). While ATP or AMP-PNP (adenylyl imidodiphosphate) binding to wild-type myosin subfragment-1 enhanced tryptophan fluorescence by approximately 15% or approximately 8%, respectively, enhancement does not occur in the mutant. This suggests that the mutation reduces lever arm movement. The mutation decreases in vitro motility of actin filaments by approximately 35%. Mutant pupal indirect flight muscles display normal myofibril assembly, myofibril shape, and double-hexagonal arrangement of thick and thin filaments. Two-day-old fibers have occasional "cracking" of the crystal-like array of myofilaments. Fibers from 1-week-old adults show more severe cracking and frayed myofibrils with some disruption of the myofilament lattice. Flight ability is reduced in 2-day-old flies compared to wild-type controls, with no upward mobility but some horizontal flight. In 1-week-old adults, flight capability is lost. Thus, altered myosin function permits myofibril assembly, but results in a progressive disruption of the myofilament lattice and flight ability. We conclude that R759 in the myosin converter domain is essential for normal ATPase activity, in vitro motility and locomotion. Our results provide the first mutational evidence that intramolecular signaling between the relay loop and converter domain is critical for myosin function both in vitro and in muscle. PMID- 20362585 TI - Mechanism of U insertion RNA editing in trypanosome mitochondria: the bimodal TUTase activity of the core complex. AB - Expression of the trypanosomal mitochondrial genome requires the insertion and deletion of uridylyl residues at specific sites in pre-mRNAs. RET2 terminal uridylyl transferase is an integral component of the RNA editing core complex (RECC) and is responsible for the guide-RNA-dependent U insertion reaction. By analyzing RNA-interference-based knock-in Trypanosoma brucei cell lines, purified editing complex, and individual protein, we have investigated RET2's association with the RECC. In addition, the U insertion activity exhibited by RET2 as an RECC subunit was compared with characteristics of the monomeric protein. We show that interaction of RET2 with RECC is accomplished via a protein-protein contact between its middle domain and a structural subunit, MP81. The recombinant RET2 catalyzes a faithful editing on gapped (precleaved) double-stranded RNA substrates, and this reaction requires an internal monophosphate group at the 5' end of the mRNA 3' cleavage fragment. However, RET2 processivity is limited to insertion of three Us. Incorporation into the RECC voids the internal phosphate requirement and allows filling of longer gaps similar to those observed in vivo. Remarkably, monomeric and RECC-embedded enzymes display a similar bimodal activity: the distributive insertion of a single uracil is followed by a processive extension limited by the number of guiding nucleotides. Based on the RNA substrate specificity of RET2 and the purine-rich nature of U insertion sites, we propose that the distributive +1 insertion creates a substrate for the processive gap-filling reaction. Upon base-pairing of the +1 extended 5' cleavage fragment with a guiding nucleotide, this substrate is recognized by RET2 in a different mode compared to the product of the initial nucleolytic cleavage. Therefore, RET2 distinguishes base pairs in gapped RNA substrates which may constitute an additional checkpoint contributing to overall fidelity of the editing process. PMID- 20362586 TI - Random walk in genome space: a key ingredient of intermittent dynamics of community assembly on evolutionary time scales. AB - Community assembly is studied using individual-based multispecies models. The models have stochastic population dynamics with mutation, migration, and extinction of species. Mutants appear as a result of mutation of the resident species, while migrants have no correlation with the resident species. It is found that the dynamics of community assembly with mutations are quite different from the case with migrations. In contrast to mutation models, which show intermittent dynamics of quasi-steady states interrupted by sudden reorganizations of the community, migration models show smooth and gradual renewal of the community. As a consequence, instead of the 1/f diversity fluctuations found for the mutation models, 1/f(2), random-walk like fluctuations are observed for the migration models. In addition, a characteristic species lifetime distribution is found: a power law that is cut off by a "skewed" distribution in the long-lifetime regime. The latter has a longer tail than a simple exponential function, which indicates an age-dependent species-mortality function. Since this characteristic profile has been observed, both in fossil data and in several other mathematical models, we conclude that it is a universal feature of macroevolution. PMID- 20362587 TI - Model of colonic inflammation: immune modulatory mechanisms in inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is an immunoinflammatory illness of the gut initiated by an immune response to bacteria in the microflora. The resulting immunopathogenesis leads to lesions in epithelial lining of the colon through which bacteria may infiltrate the tissue causing recurring bouts of diarrhea, rectal bleeding, and malnutrition. In healthy individuals such immunopathogenesis is avoided by the presence of regulatory cells that inhibit the inflammatory pathway. Highly relevant to the search for treatment strategies is the identification of components of the inflammatory pathway that allow regulatory mechanisms to be overridden and immunopathogenesis to proceed. In vitro techniques have identified cellular interactions involved in inflammation regulation crosstalk. However, tracing immunological mechanisms discovered at the cellular level confidently back to an in vivo context of multiple, simultaneous interactions has met limited success. To explore the impact of specific interactions, we have constructed a system of 29 ordinary differential equations representing different phenotypes of T-cells, macrophages, dendritic cells, and epithelial cells as they move and interact with bacteria in the lumen, lamina propria, and lymphoid tissue of the colon. Simulations revealed the positive inflammatory feedback loop formed by inflammatory M1 macrophage activation of T cells as a driving force underlying the immunopathology of IBD. Furthermore, strategies that remove M1 from the site of infection, by either (i) increasing its potential to switch to a regulatory M2 phenotype or (ii) increasing the rate of reversion (for M1 and M2 alike) to a resting state, cease immunopathogenesis even as bacteria are eliminated by other inflammatory cells. Based on these results, we identify macrophages and their mechanisms of plasticity as key targets for mucosal inflammation intervention strategies. In addition, we propose that the primary mechanism behind the association of PPARgamma mutation with IBD is its ability to mediate the M1 to M2 switch. PMID- 20362588 TI - Global and local prediction of protein folding rates based on sequence autocorrelation information. AB - To understand the folding behavior of proteins is an important and challenging problem in modern molecular biology. In the present investigation, a large number of features representing protein sequences were developed based on sequence autocorrelation weighted by properties of amino acid residues. Genetic algorithm (GA) combined with multiple linear regression (MLR) was employed to select significant features related to protein folding rates, and to build global predictive model. Moreover, local lazy regression (LLR) method was also used to predict the protein folding rates. The obtained results indicated that LLR performed much better than the global MLR model. The important properties of amino acid residues affecting protein folding rates were also analyzed. The results of this study will be helpful to understand the mechanism of protein folding. Our results also demonstrate that the features of amino acid sequence autocorrelation is effective in representing the relationship between protein sequence and folding rates, and the local method is a powerful tool to predict the protein folding rates. PMID- 20362589 TI - Modeling the spontaneous activity in suprachiasmatic nucleus neurons: role of cation single channels. AB - A population of interconnected neurons of the mammalian suprachiasmatic nuclei (SCN) controls circadian rhythms in physiological functions. In turn, a circadian rhythm of individual neurons is driven by intracellular processes, which via activation of specific membrane channels, produce circadian modulation of electrical firing rate. Yet the membrane target(s) of the cellular clock have remained enigmatic. Previously, subthreshold voltage-dependent cation (SVC) channels have been proposed as the membrane target of the cellular clock responsible for circadian modulation of the firing rate in SCN neurons. We tested this hypothesis with computational modeling based on experimental results from on cell recording of SVC channel openings in acutely isolated SCN neurons and long term continuous recording of activity from dispersed SCN neurons in a multielectrode array dish (MED). The model reproduced the circadian behavior if the number of SVC channels or their kinetics were modulated in accordance with protein concentration in a model of the intracellular clock (Scheper et al., 1999. J. Neurosci. 19, 40-47). Such modulation changed the average firing rate of the model neuron from zero ("subjective-night" silence) up to 18 Hz ("subjective day" peak). Furthermore, the variability of interspike intervals (ISI) and the circadian pattern of firing rate (i.e. silence-to-activity ratio and shape of circadian peaks) are in reasonable agreement with experimental data obtained in dispersed SCN neurons in MED. These results suggest that the variability of ISI in intact SCN neurons is mostly due to stochastic single-channel openings, and that the circadian pattern of the firing rate is specified by threshold properties of dependence of the spontaneous firing rate on the number of single channels (R-N relationship). This plausible mathematical modeling supports the hypothesis that SVC channels could be a critical element in circadian modulation of firing rate in SCN neurons. PMID- 20362590 TI - A model investigation of the impact of ventilation-perfusion mismatch on oxygenation during apnea in preterm infants. AB - Ventilation-perfusion (V/Q) mismatch is a prominent feature of preterm infants and adults with lung disease. V/Q mismatch is known to cause arterial hypoxemia under steady-state conditions, and has been proposed as the cause of rapid arterial oxygen desaturation during apnea. However, there is little evidence to support a role for V/Q mismatch in the dynamic changes in arterial oxygenation that occur during apnea. Using a mathematical model, we quantified the effect of V/Q mismatch on the rate of desaturation during apnea to ascertain whether it could lead to rates of up to 10%s(-1) as observed in preterm infants. We used a lung-body model for the preterm infant that incorporated 50 parallel alveolar capillary units that were ventilated and perfused with the severity of V/Q mismatch (sigma) defined conventionally according to sigma=S.D. of the distribution of V/Q ratios. Average desaturation rate 10s from apnea onset was strongly elevated with worsening V/Q mismatch as a result of an earlier desaturation of low V/Q units compared with high V/Q units. However, V/Q mismatch had little impact after apnea onset, with peak desaturation rate only substantially increased if mismatching caused a lowered resting arterial O(2) saturation. In conclusion, V/Q mismatch causes a more immediate onset of desaturation during apnea, and therefore places preterm infants and adults with lung disease at risk of hypoxemic dips. However, V/Q mismatch does not accelerate desaturation rate beyond apnea onset and cannot, therefore, explain the rapid desaturation observed during recurrent apnea in preterm infants. PMID- 20362591 TI - On invariant property in population statistics. AB - Concept of aging is developed to yield a relationship between life spans and the velocity of aging. The mathematical analysis shows that the mean extent of the advancement of aging throughout one's life is conserved, or equivalently, the product of the mean life span, T, and the mean rate of aging, v (A), is constant, T x v (A)=k. The result is in harmony with our experiences: it accounts for the unlimited replicability of tumor cells, and predicts the prolonged life spans of hibernating hamsters according to the equation, T congruent with [Formula in text] is a constant and chi denotes the total fraction of hibernation periods), in accordance with the Lyman and co-workers experiment. Comparing the present result and the empirical relationship between life spans of various mammals and basal metabolic rates, it is suggested that the mean rate of aging is intimately connected with the mean basal metabolic rate. With the help of this information, we inquire the reason of the difference in mean life spans between women and men, the result showing that the relative mean life span of women to men is T(women)/T(men) congruent with 1.08 for various nations, which is close to the corresponding relative value of the basal metabolic rate. The present analysis suggests, however, that this relationship between life spans and basal metabolic rates must be treated with caution. PMID- 20362593 TI - Modulation of the blood-brain barrier permeability by plasma glycoprotein orosomucoid. AB - Previous studies have shown that the glycoprotein orosomucoid modulates permeability of peripheral microvessels to charged molecules by contributing to the net charge on the microvessel wall. To investigate whether or not orosomucoid also modulates the permeability of the blood-brain barrier (BBB) by a similar mechanism, we measured the permeability (P) of rat pial microvessels to similar sized molecules with different charges: alpha-lactalbumin (-10, Stokes radius 2.08 nm) and ribonuclease (+4, Stokes radius 2.01 nm). Tests were performed under control conditions with a Ringer-BSA (bovine serum albumin) perfusate and with 0.1mg/ml orosomucoid in Ringer-BSA perfusate. The pial circulation was observed through a section of frontoparietal bones thinned with a micro-grinder, and P was determined using a quantitative fluorescence video microscopy. In the absence of orosomucoid, the permeability of pial microvessels to positively charged ribonuclease was 4-fold that to negatively charged alpha-lactalbumin. In contrast, in the presence of orosomucoid, permeability to ribonuclease was 12 fold that to alpha-lactalbumin. On the basis of these experimental data, our theoretical model predicted that the charge density of the endothelial glycocalyx layer at the luminal surface of the BBB increased 2.8-fold in the presence of 0.1 mg/ml orosomucoid, while the charge density of the BBB basement membrane increased 1.8-fold, compared to their control values. Our results indicate that orosomucoid can modulate the permeability of the BBB to charged molecules by adding negative charge to the matrix components of the BBB. PMID- 20362592 TI - Vascular endothelial growth factor (VEGF)-A: role on cardiac angiogenesis following myocardial infarction. AB - The current study is to determine the regulatory role of VEGF-A in cardiac angiogenesis following myocardial infarction (MI). Cardiac angiogenic response and temporal/spatial expression of VEGF-A/VEGF receptors (VEGFR) were examined at 1, 2, 6, 12 h and 1, 2, 3, 4, 7, 14, and 28 days postMI. We found that following MI, newly formed vessels first appeared at the border zone between noninfarcted and infarcted myocardium as early as day 3 and subsequently in the infarcted myocardium. Vascular density in the infarcted myocardium peaked at day 7 and then gradually declined. VEGF-A mRNA started to increase at the border zone at 2 h postMI, reached peak at 12 h, declined at day 1, and returned to normal levels at day 2 and thereafter. VEGF-A protein levels at the border zone were only increased during day 1 postMI. VEGF-A within the infarcted myocardium levels, however, was persistently suppressed postMI. VEGFR expression was significantly increased only at the border zone at day 1, but not in the later stages. The expression of VEGF-A/VEGFR remained unchanged in the noninfarcted myocardium. Thus, the early rise of VEGF-A/VEGFR at the border zone suggests that VEGF-A initiates the cardiac angiogenic response postMI, but short-lived VEGF-A/VEGFR activation at the border zone and consistently suppressed VEGF-A within the infarcted myocardium suggests that VEGF-A may not be crucial to the later stages of angiogenesis. PMID- 20362594 TI - The type IV phosphodiesterase inhibitor rolipram disturbs expression and extinction of conditioned fear in mice. AB - Recent studies suggest that intracellular signaling pathways involving cyclic adenosine monophosphate (cAMP) may be related to fear processing and long-term memory formation. The type IV phosphodiesterase (PDE4) inhibitor rolipram prevents breakdown of cAMP, enhances long-term memory and may reduce anxiety. In the present study we investigated the role of rolipram in the expression (0, 0.2, or 1 mg/kg), acquisition (0, 0.03, 0.2 or 1 mg/kg), and extinction (0, 0.03, 0.2, 1 mg/kg) of fear using a fear-potentiated startle paradigm in mice. It was shown that rolipram reduced the expression (Experiment 1), did not influence acquisition (Experiment 2) and disturbed between-session extinction (Experiments 3 and 4) of fear responses to conditioned tones. Because within-session extinction was not impaired by rolipram and because low (i.e. 0.03 and 0.2 mg/kg) doses strongly affected extinction but not expression of fear, these findings suggest that the effect of rolipram on extinction is not directly dependent on its effect on fear expression. Taken together, these experiments indicate that preventing breakdown of cAMP interferes with the expression and extinction consolidation of conditioned fear. PMID- 20362595 TI - Acquired prosopagnosia as a face-specific disorder: ruling out the general visual similarity account. AB - Prosopagnosia is classically defined as a disorder of visual recognition specific to faces, following brain damage. However, according to a long-standing alternative view, these patients would rather be generally impaired in recognizing objects belonging to visually homogenous categories, including faces. We tested this alternative hypothesis stringently with a well-documented brain damaged prosopagnosic patient (PS) in three delayed forced-choice recognition experiments in which visual similarity between a target and its distractor was manipulated parametrically: novel 3D geometric shapes, morphed pictures of common objects, and morphed photographs of a highly homogenous familiar category (cars). In all experiments, PS showed normal performance and speed, and there was no evidence of a steeper increase of error rates and RTs with increasing levels of visual similarity, compared to controls. These data rule out an account of acquired prosopagnosia in terms of a more general impairment in recognizing objects from visually homogenous categories. An additional experiment with morphed faces confirmed that PS was specifically impaired at individual face recognition. However, in stark contrast to the alternative view of prosopagnosia, PS was relatively more impaired at the easiest levels of discrimination, i.e. when individual faces differ clearly in global shape rather than when faces were highly similar and had to be discriminated based on fine-grained details. Overall, these observations as well as a review of previous evidence, lead us to conclude that this alternative view of prosopagnosia does not hold. Rather, it seems that brain damage in adulthood may lead to selective recognition impairment for faces, perhaps the only category of visual stimuli for which holistic/configural perception is not only potentially at play, but is strictly necessary to individualize members of the category efficiently. PMID- 20362596 TI - Using stimulus form change to understand memorial familiarity for pictures and words in patients with mild cognitive impairment and Alzheimer's disease. AB - Although it is generally accepted that patients with amnestic mild cognitive impairment (aMCI) and patients with Alzheimer's disease (AD) have significantly impaired recollection, recent evidence has been mixed as to whether these patients demonstrate impaired memorial familiarity. Recent work suggests that familiarity may remain intact for pictures, but not for words. Further, a recent event-related potential (ERP) study suggests that enhanced conceptual processing of pictures may underlie this intact familiarity. However, to date there has been no direct comparison of perceptual and conceptual-based familiarity for pictures and words in patients with aMCI and AD. To investigate this issue, patients with aMCI, patients with AD, and healthy older adults underwent four study-test conditions of word-word, picture-picture, word-picture, and picture-word. When stimuli undergo form change, it has been suggested that only conceptual processing can help support recognition in the absence of recollection. Our results showed that patients successfully relied on perceptual and conceptual based familiarity to improve recognition for the within format conditions over the across format conditions. Further, results suggested that patients with aMCI and AD are able to use enhanced conceptual processing of pictures compared to words to allow them to overcome the deleterious effects of form change in a similar manner as controls. These results help us begin to understand which aspects of memory are impaired and which remain relatively intact in patients with aMCI and AD. This understanding can then in turn help us to assess, conceptualize, and build behavioral interventions to help treat these patients. PMID- 20362597 TI - Children's executive functions: are they poorer after very early brain insult. AB - Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability perspective, we investigated whether skills developing later in childhood, for example, executive functions (EF), would be at greater risk of disruption from EBI. The aim of this study was to investigate EF in children sustaining EBI at different developmental stages. We expected that brain insult during gestation and infancy, before the emergence of EF, would lead to global EF deficits. In contrast, we predicted that brain injury in late childhood would have fewer consequences. Using a cross-sectional, retrospective, group design we compared six groups of children (Total N=164), with a history of brain insult and documented focal brain pathology, aged 10-16 years on a range of measures of EF. Groups were based on age of EBI: (1) Congenital; (2) Peri-natal; (3) Infancy; (4) Preschool; (5) Middle Childhood; and (6) Late Childhood. Children with EBI were at increased risk for impairment across all aspects of EF. Presence of seizures and/or frontal pathology were not predictive of outcome, but age at insult was. Children sustaining EBI before age 3 recorded more global and severe EF deficits, while children with later EBI performed closer to normal expectations. With the exception of attentional control, skills emerging at time of insult were found to be more vulnerable to disruption than those previously established, supporting the 'early vulnerability' model for EBI. PMID- 20362598 TI - How should I decide? The neural correlates of everyday moral reasoning. AB - The present fMRI study is the first that investigates everyday moral conflict situations in which a moral standard clashes with a personal desire. In such situations people have to decide between a morally guided and a hedonistic behaviour. Twelve healthy subjects were presented with verbal stories describing conflicts with either moral or neutral content. The moral stories described conflicts requiring a decision between a personal desire and a conflicting moral standard, whereas the neutral conflicts required a decision between two conflicting personal desires. When compared to neutral conflicts, moral conflicts elicited higher activity in a wide spread neural network including the medial frontal cortex, the temporal cortex and the temporo-parietal junction and the posterior cingulate cortex. Further analyses of the moral conflicts revealed that hedonistic decisions in contrast to morally guided decisions were associated with significantly higher rankings of uncertainty and unpleasant emotions and induced significant more activation in the amygdala/parahippocampal region. The present results generalise findings on the neuroscience of moral understanding by extending it to everyday moral decisions. Furthermore, the results show that the amydala region plays a central role in the processing of negative emotional consequences associated with immoral decisions. PMID- 20362599 TI - Learning task affects ERP-correlates of the own-race bias, but not recognition memory performance. AB - People are generally better in recognizing faces from their own ethnic group as opposed to faces from another ethnic group, a finding which has been interpreted in the context of two opposing theories. Whereas perceptual expertise theories stress the role of long-term experience with one's own ethnic group, race feature theories assume that the processing of an other-race-defining feature triggers inferior coding and recognition of faces. The present study tested these hypotheses by manipulating the learning task in a recognition memory test. At learning, one group of participants categorized faces according to ethnicity, whereas another group rated facial attractiveness. Subsequent recognition tests indicated clear and similar own-race biases for both groups. However, ERPs from learning and test phases demonstrated an influence of learning task on neurophysiological processing of own- and other-race faces. While both groups exhibited larger N170 responses to Asian as compared to Caucasian faces, task dependent differences were seen in a subsequent P2 ERP component. Whereas the P2 was more pronounced for Caucasian faces in the categorization group, this difference was absent in the attractiveness rating group. The learning task thus influences early face encoding. Moreover, comparison with recent research suggests that this attractiveness rating task influences the processes reflected in the P2 in a similar manner as perceptual expertise for other-race faces does. By contrast, the behavioural own-race bias suggests that long-term expertise is required to increase other-race face recognition and hence attenuate the own-race bias. PMID- 20362600 TI - The role of inferior frontal cortex in belief-bias reasoning: an rTMS study. AB - The belief-bias effect in syllogistic reasoning refers to the tendency for subjects to be erroneously biased when logical conclusions are incongruent with belief about the world. This study examined the role of inferior frontal cortex (IFC) in belief-bias reasoning using repetitive transcranial magnetic stimulation (rTMS). We used an off-line rTMS method to disrupt IFC activity transiently. Right IFC stimulation significantly impaired incongruent reasoning performance, enhancing the belief-bias effect. Subjects whose right IFC was impaired by rTMS may not be able to inhibit irrelevant semantic processing in incongruent trials. Although left IFC stimulation impaired congruent reasoning, it paradoxically facilitated incongruent reasoning performance, eliminating the belief-bias effect. Subjects whose left IFC was impaired by rTMS may not suffer from interference by irrelevant semantic processing. This study demonstrates for the first time the roles of left and right IFC in belief-bias reasoning using an rTMS approach. PMID- 20362601 TI - Visuo-motor and cognitive procedural learning in children with basal ganglia pathology. AB - We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage. PMID- 20362602 TI - Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis. AB - Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [(3)H] leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [(3)H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-kappaB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4. PMID- 20362603 TI - Nucleotide sequence determines the accelerated rate of point mutations. AB - Although the theory of evolution was put forth about 150 years ago our understanding of how molecules drive evolution remains poor. It is well established that proteins evolve at different rates, essentially based on their functional role and three-dimensional structure. However, the highly variable rates of evolution of different proteins - especially the rapidly evolving ones - within a single organism are poorly understood. Using examples of genes for fast evolving toxins and human hereditary diseases, we show for the first time that specific nucleotide sequences appear to determine point mutation rates. Based on mutation rates, we have classified triplets (not just codons) into stable, unstable and intermediate groups. Toxin genes contain a relatively higher percentage of unstable triplets in their exons compared to introns, whereas non toxin genes contain a higher percentage of unstable triplets in their introns. Thus the distribution of stable and unstable triplets is correlated with and may explain the accelerated evolution of point mutations in toxins. Similarly, at the genomic level, lower organisms with genes that evolve faster contain a higher percentage of unstable triplets compared to higher organisms. These findings show that mutation rates of proteins, and hence of the organisms, are DNA sequence dependent and thus provide a proximate mechanism of evolution at the molecular level. PMID- 20362604 TI - Analysis of camelid IgG for antivenom development: Serological responses of venom immunised camels to prepare either monospecific or polyspecific antivenoms for West Africa. AB - Snake envenoming is a significant cause of mortality and morbidity in sub-Saharan Africa. The only effective treatment, antivenom, has been in short supply since the 1990s. Whilst the humanitarian response by some antivenom producers has significantly improved the situation, strategies to ensure the long term stability of antivenom supply are still necessary. We are investigating whether the potential safety and logistic advantages of camel IgG antivenom can be exploited to improve antivenom provision in many countries where snakebite is endemic. This study assessed the IgG titre, specificity and avidity of camels immunised with either individual venom or a mixture of venoms from the three most medically important snakes of West Africa, the saw-scale viper (Echis ocellatus), the puff adder (Bitis arietans) and the spitting cobra (Naja nigricollis). Seven of the eight immunised camels generated IgG titres and avidities comparable to, or exceeding, that of commercial equine and ovine antivenoms that are highly effective in envenomed patients. In this, the first of a series of reports on the potential utility of camelid IgG antivenom, we describe an immunisation protocol that induced potent, sustained serological response of very high antibody avidity. These attributes suggest, from an immunological perspective, that camel IgG antivenoms should be as efficacious as current equine and ovine antivenoms. PMID- 20362605 TI - A novel TTX-producing Aeromonas isolated from the ovary of Takifugu obscurus. AB - Puffer fish (Takifugu obscurus) from the Yangtze River of China were screened for tetrodotoxin-producing bacteria. An Aeromonas strain was isolated from the ovary of the puffer fish and was shown to produce tetrodotoxin; this strain was denoted Ne-1. The identity of tetrodotoxin produced by strain Ne-1 was confirmed by mouse bioassay, high performance liquid chromatography coupled with mass chromatography (LC-MS), and ELISA. Strain Ne-1 was characterized morphologically, biochemically, and by 16S rDNA phylogenetic analysis; these analyses suggested that strain Ne-1 is closely related to Aeromonas molluscorum. Given that strain Ne-1 was isolated from the ovary of T. obscurus, we propose that the TTX-producing Aeromonas sp. is a parasite or symbiotic bacterium rather than a sample contaminant. Collectively, our studies suggest that Aeromonas sp. strain Ne-1 produces tetrodotoxin in T. obscurus. PMID- 20362606 TI - A defensin antimicrobial peptide from the venoms of Nasonia vitripennis. AB - Although many antimicrobial components (i.e. antimicrobial peptides) have been found in many social Hymenoptera venoms, no antimicrobial compound is purified and characterized from parasitic Hymenoptera. From the venoms of the ectoparasitic wasp, Nasonia vitripennis, a defensin-like antimicrobial peptide named defensin-NV was purified and characterized. Defensin-NV is composed of 52 amino acid residues including 6 cysteines forming 3 disulfide bridges. Its amino acid sequence is VTCELLMFGGVVGDSACAANCLSMGKAGGSCNGGLCDCRKTTFKELWDKRFG. By BLAST search, defensin-NV showed significant sequence similarity to other insect defensin antimicrobial peptides. Defensin-NV exerted strong antimicrobial activity against tested microorganisms including Gram-positive bacteria, Gram negative bacteria and fungi. The cDNA encoding defensin-NV was cloned from the venom reservoir cDNA library of N. vitripennis. The current work firstly purified and characterized an antimicrobial peptide from parasitic Hymenoptera. PMID- 20362607 TI - Microcystins in South American aquatic ecosystems: Occurrence, toxicity and toxicological assays. AB - The acute poisoning of chronic renal patients during hemodialysis sessions in 1996 in Caruaru City (Pernambuco State, Brazil) stimulated an intensive search for the cause of this severe complication. This search culminated in the identification of microcystins (MC), hepatotoxic cyclic heptapeptides produced by cyanobacteria, as the causative agents. More than ten years later, additional research data provides us with a better understanding of the factors related to cyanobacterial bloom occurrence and production of MC in Brazil and other South American countries. The contamination of water bodies and formation of toxic blooms remains a very serious concern, especially in countries in which surface water is used as the main source for human consumption. The purpose of this review is to highlight the discoveries of the past 15 years that have brought South American researchers to their current level of understanding of toxic cyanobacteria species and that have contributed to their knowledge of factors related to MC production, mechanisms of action and consequences for human health and the environment. PMID- 20362608 TI - Nutrition and aging. PMID- 20362609 TI - Identifying sociodemographic differences in Intimate Partner Violence among immigrant and native women in Spain: a cross-sectional study. AB - OBJECTIVES: To analyze whether sociodemographics and social support have a different or similar effect on the likelihood of Intimate Partner Violence in immigrants and natives, and to estimate prevalences and associations between different types of IPV depending on women's birthplace. METHODS: Cross-sectional study of 10,048 women (18-70 years) attending primary healthcare in Spain (2006 2007). OUTCOME: Current Intimate Partner Violence (psychological, physical and both). Sociodemographics and social support were considered first as explicative and later as control variables. RESULTS: Similar Intimate Partner Violence sociodemographic and social support factors were observed among immigrants and natives. However, these associations were stronger among immigrants, except in the case of poor social support (adjusted odds ratio natives 4.36 and adjusted odds ratio immigrants 4.09). When these two groups were compared, immigrants showed a higher likelihood of IPV than natives (adjusted odds ratios 1.58). CONCLUSION: Immigrant women are in a disadvantaged Intimate Partner Violence situation. It is necessary that interventions take these inequalities into account. PMID- 20362610 TI - Why should population attributable fractions be periodically recalculated? An example from cardiovascular risk estimation in southern Europe. AB - OBJECTIVE: To determine the effect of age and study period on coronary heart disease (CHD) risk attributable to cardiovascular risk factors. METHODS: A cohort of cardiovascular disease (CVD)-free randomly participants from Girona (Spain) aged 35-74 years recruited in 1995 and 2000 and followed for an average of 6.9 years. A survey conducted in the same area in 2005 was also used for the analysis. Smoking, hypertension, diabetes, sedentary lifestyle, obesity, total cholesterol > or = 240 mg/dl, low-density lipoprotein (LDL) cholesterol > or = 160 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl were the risk factors considered. The composite end-point included myocardial infarction, angina pectoris, and CHD death. RESULTS: LDL cholesterol had the highest potential for CHD prevention between 35 and 74 years [42% (95% Confidence Interval: 23,58)]. The age-stratified analysis showed that the population attributable risk (PAF) for smoking was 64% (30,80) in subjects < 55 years; for those > or = 55 years, the PAF for hypertension was 34% (1,61). The decrease observed between 1995 and 2005 in the population's mean LDL cholesterol level reduced that PAF in all age groups. CONCLUSION: Overall, LDL cholesterol levels had the highest potential for CHD prevention. Periodic PAF recalculation in different age groups may be required to adequately monitor population trends. PMID- 20362611 TI - The prosocial psychopath: explaining the paradoxes of the creative personality. AB - The literature on the creative personality is curiously equivocal in its characterization of the traits supposedly possessed by eminent creators. While acclaimed as revolutionary and pioneering visionaries, the same category of people can come across as unsocialized and discomfiting even to their close associates and admirers. This paper suggests that these ambiguities can be addressed by appealing to the potential psychobiological mechanisms that can give rise to the expression of both creative ability and "antisocial" traits. Work on latent inhibition, the somatic marker hypothesis, Eysenck's biosocial theory of crime and the dopamine hypothesis of addiction are reviewed and integrated into a model that examines the role of dopamine as a critical agent in the creative personality system. Finally, testable hypotheses stemming from the model are proposed. PMID- 20362612 TI - Bacterial translocation across ePTFE vascular graft surfaces. AB - OBJECTIVES: Vascular graft infections arise from bacterial colonization of either the external or internal graft surfaces. We assessed whether methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli could translocate through pores of ePTFE grafts. METHODS: To assess translocation from the internal to the external surface, we placed 10(5) cfu of bacterial suspension inside ePTFE graft segments and suspended them in sterile broth for 72 h. To assess translocation from the external to the internal surface, we placed sterile broth inside ePTFE segments, and incubated them for 72 h in a bacterial suspension (10(5) cfu/mL). At 72 h, in addition to culturing the sterile broth and bacterial suspensions, the external and internal surfaces were first qualitatively cultured separately and then quantitatively cultured by sonication. RESULTS: At 72 h, the sterile broth remained sterile. The bacterial suspensions yielded 10(7)-10(9) cfu/mL. Graft cultures indicated that colonization of one surface with either organism did not result in bacterial translocation to the other surface. Quantitative bacterial counts of the external vs. internal surfaces were significantly different (p < 0.01). CONCLUSIONS: MRSA and E. coli do not translocate across ePTFE graft surfaces. These in-vitro findings help elucidate the pathogenesis of graft infections and prompt conduction of validation studies in-vivo. PMID- 20362614 TI - The Matrix: a new tool for probing the whisker-to-barrel system with natural stimuli. AB - The whisker to barrel system in rodents has become one of the major models for the study of sensory processing. Several tens of whiskers (or vibrissae) are distributed in a regular manner on both sides of the snout. Many tactile discrimination tasks using this system need multiple contacts with more than one whisker to be solved. With the aim of mimicking those multi-whisker stimuli during electrophysiological recordings, we developed a novel mechanical stimulator composed of 24 independent multi-directional piezoelectric benders adapted to the five rows and the five caudal arcs of the rat whisker pad. The most widely used technology for producing mechanical deflections of the whiskers is based on piezoelectric benders that display a non-linear behavior when driven with high frequency input commands and, if not compensated, show high unwanted ringing at particular resonance frequencies. If not corrected, this non-linear behavior precludes the application of high frequency deflections and the study of cortical responses to behaviorally relevant stimuli. To cope with the ringing problem, a mechanical and a software based solutions have been developed. With these corrections, the upper bound of the linear range of the bender is increased to 1 kHz. This new device allows the controlled delivery of large scale natural patterns of whisker deflections characterized by rapid high frequency vibrations of multiple whiskers. PMID- 20362613 TI - Sterols and sphingolipids: dynamic duo or partners in crime? AB - One manner in which eukaryotic cells respond to their environments is by optimizing the composition and proportions of sterols and sphingolipids in membranes. The physical association of the planar ring of sterols with the acyl chains of phospholipids, particularly sphingolipids, produces membrane micro heterogeneity that is exploited to coordinate several crucial pathways. We hypothesize that these lipid molecules play an integrated role in human disease; when one of the partners is mis-regulated, pathology frequently ensues. Sterols and sphingolipid levels are not coordinated by the action of a single master regulator, however the cross-talk between their metabolic pathways is considerable. We describe our perspectives on the key components of synthesis, catabolism and transport of these lipid partners with an emphasis on evolutionarily conserved reactions that produce disease states when defective. PMID- 20362615 TI - Validation of a method for preparing influenza H5N1 simulated samples. AB - Avian influenza virus type A subtype H5N1 and potentially other novel influenza A viruses continue to pose a concern with mutation into a form easily transmitted between humans. The ability to rapidly detect and characterize influenza viruses, and distinguish seasonal and novel influenza A viruses such as H5N1, remains important to minimize morbidity and mortality in humans. As with other rare and emerging viral pathogens, clinical specimens from persons with H5N1 infections are extremely rare. Consequently, development of standardized methods and accepted criteria are necessary for both ensuring the validity of available diagnostic methods and for assessing the potential of new diagnostic tests that can detect and differentiate H5N1 and other novel influenza A viruses. Additionally, genotypic and antigenic evolution of H5N1 poses a challenge with maintaining updated reference virus strains. In this report, a method for preparing simulated samples using defined procedures and carefully selected H5N1 virus strains is described, and the reliability for using these samples in an evaluation protocol with a laboratory test for differentiating H5N1 virus from other influenza A viruses is evaluated. PMID- 20362616 TI - Ageing and immunity: addressing immune senescence to ensure healthy ageing. AB - Among the greatest achievements of the 20th century, prolongation of life expectancy has been the result of improved health conditions, decreased childhood mortality, lower incidence of infectious diseases. The consequence is the rapid ageing of the world population, with the elderly representing over 25% of the entire population by the year 2030, of which 75% living in less developed countries. Ageing thus represents one of the major public health challenges of the 21st century. Indeed, unhealthy ageing and frailty of the aged population has an important impact on the economic development and social costs of a country, a problem even more acute in less developed countries. A better knowledge of immune senescence and the design of customised vaccination strategies for the elderly are the immediate challenges posed to scientists and physicians. The conference "Ageing and immunity", recently held in Siena (Italy), has addressed these issues and defined the global strategic priorities for research and health policies aimed at ensuring healthy ageing. PMID- 20362618 TI - Regrettable lack of definition of the "well tolerated" vaccine. PMID- 20362617 TI - Universal indirect enzyme-linked immunosorbent assay for monitoring of human and animal brucellosis in Kazakhstan. AB - Combinations of conventional serological methods and new ELISA procedures were evaluated to develop the most efficient and effective diagnostics for the detection of brucellosis in humans and animals. Sera from humans (n=249) and animals (n=99) were collected from brucellosis endemic areas (Zhambyl district and Enbekshi-Kazakh district of Almaty region in Kazakhstan) for serologic analysis. Sera from the humans reacted positively in the RBT (38.5%), SAT (43.3%), iELISA (42.5%) while sera from the animals reacted positively in RBT (79.8%), SAT (89.9%), CF (87.8%), iELISA (100%). Greater seropositivity was detected in animals as compared to human samples. All positive sera were also evaluated on an indirect ELISA (iELISA). Bacterial isolation was attempted on seropositive human sera. Our data indicate that the combination of conventional serological tests (SAT and CF), combined with the iELISA is optimal for the processing of large numbers of samples and the most efficient detection of human and animal brucellosis. PMID- 20362619 TI - Designing vaccines against cattle brucellosis. AB - The article presents the results from a study of two new vaccines against cattle brucellosis from Brucella abortus cultures. One of these is a live dry vaccine prepared from a weakly agglutinogenic strain in the SR form and the second, an inactivated adjuvant vaccine from an non-agglutinogenic strain in the R form. The immunogenic properties of the vaccines were studied in three tests on heifers with infection by a virulent B. abortus culture. The vaccines passed the farm scale testing and were accepted in veterinary practice. PMID- 20362620 TI - Vaccination strategies for managing brucellosis in Yellowstone bison. AB - Concerns over migratory bison (Bison bison) at Yellowstone National Park transmitting brucellosis (Brucella abortus) to cattle herds on adjacent lands led to proposals for bison vaccination. We developed an individual-based model to evaluate how brucellosis infection might respond under alternate vaccination strategies, including: (1) vaccination of female calves and yearlings captured at the park boundary when bison move outside the primary conservation area; (2) combining boundary vaccination with the remote delivery of vaccine to female calves and yearlings distributed throughout the park; and (3) vaccinating all female bison (including adults) during boundary capture and throughout the park using remote delivery of vaccine. Simulations suggested Alternative 3 would be most effective, with brucellosis seroprevalence decreasing by 66% (from 0.47 to 0.16) over a 30-year period resulting from 29% of the population receiving protection through vaccination. Under this alternative, bison would receive multiple vaccinations that extend the duration of vaccine protection and defend against recurring infection in latently infected animals. The initial decrease in population seroprevalence will likely be slow due to high initial seroprevalence (40-60%), long-lived antibodies, and the culling of some vaccinated bison that were subsequently exposed to field strain Brucella and reacted positively on serologic tests. Vaccination is unlikely to eradicate B. abortus from Yellowstone bison, but could be an effective tool for reducing the level of infection. Our approach and findings have applicability world-wide for managers dealing with intractable wildlife diseases that cross wildlife-livestock and wildlife-human interfaces and affect public health or economic well-being. PMID- 20362621 TI - Increasing influenza vaccination rates: where is the behaviour change theory? PMID- 20362622 TI - Attenuation of defined Brucella melitensis wboA mutants. AB - Rough Brucella mutants have been sought as vaccine candidates because they do not induce seroconversion. In this study, two defined nonreverting rough mutants were derived from virulent Brucella melitensis strain 16M: a wboA deletion mutant designated WRR51 and a wboA purEK dual deletion mutant designated WRRP1. Strain WRRP1 exhibited reduced survival in human monocyte-derived macrophages (hMDMs) compared with parent strain WRR51 or with DeltapurEK strain WR201. Strain WRRP1 persisted for 1 week or less in BALB/c mice after intraperitoneal infection, while less severe attenuation was exhibited by the two single mutants in this model. Trans complementation of wboA restored the survival of WRR51 in hMDMs comparable to strain 16M and the survival of WRRP1 comparable to strain WR201. PMID- 20362623 TI - Epidemiological study of Brucellosis in cattle, immunized with Brucella abortus RB51 vaccine in endemic zones. AB - In this study the behavior of the Brucella abortus RB51 vaccine was evaluated in bovine herds, with different prevalence of Brucellosis. A prospective longitudinal study was made, in two dairies, one of low prevalence (9%) with 538 cows, and the other of high prevalence (15%) with 612 cows. The cattle were vaccinated twice 90 days apart with RB51 at a dose of 1*10(9)cfu/ml. The monthly incidence was determined during 660 days of observation. In the low prevalence dairy, all positive animals were eliminated as soon as they were diagnosed as positive and in this herd the number of new cases decreased to less than 1% between days 120, and day 660. In the dairy with high prevalence, positive cows were not eliminate resulting in the herd increasing its incidence by the end of the first year. Once positive animals were eliminated the incidence diminishes by day 660 to less of 1%. The odds ratio (OR) in the group of cows with abortion history, in the low prevalence dairy, was of 4.5 (1.2; 16.6), in the dairy ranch with high prevalence it presented an OR of 3.6 (1.5; 8.5). The conclusion from this study was that in brucellosis endemic zones, vaccination with RB51 by itself is not enough to control disease. It is mandatory that the initial elimination of all positive cows at the time of vaccination, the continued elimination of all new positive animals be adhered to for long periods of time. PMID- 20362624 TI - Immunopotentiation of live brucellosis vaccine by adjuvants. AB - In a series of studies in SPF and conventional guinea pigs, various adjuvants (larifan, polyoxidonium-PO, natrium thiosulphate-NT, TNF-beta and Ribi adjuvant system-RAS) were evaluated for their ability to enhance immune responses to the live brucellosis vaccine, Brucella abortus strain 82-PS (penicillin-sensitive). Combining adjuvants with S82-PS increased synthesis of antibodies against rough (R) and smooth (S) Brucella antigens. Dynamics and levels of antibodies differed dependent upon the adjuvant. Adjuvants enhanced cell-mediated responses to S82 PS, and phagocytosis by macrophages. Humoral and cellular immune responses stimulated by the adjuvants correlated with increased vaccine protection against experimental challenge. The highest protection was demonstrated by combining TNF beta or PO with S82-PS. Our data demonstrates the potential of adjuvants to improve immunogenic properties of live brucellosis vaccines. PMID- 20362625 TI - Development and characterization of a modified Komarov's bullet for ballistic delivery of live Brucella abortus strains 82 and 19 to cattle and bison. AB - In this study a modified Komarov's bullet was developed to remotely deliver live brucellosis vaccines (Brucella abortus 82 and Brucella abortus 19). After modification, the bullet payload could carry the desired dose (10(11)CFU) of vaccine. As the bullet components were toxic to the live bacteria, a special protective coating was developed for the bullet inner surface that maintained vaccine viability. Vaccine viability was not influenced by ballistic delivery and the characteristics of the modified bullet allowed accurate delivery at distances of 100m. Intramuscular ballistic delivery of the modified Komarov's bullet into live cattle and bison was not associated with detrimental clinical effects. The modified bullet penetrated approximately 3-5.5cm into muscular tissue. At necropsy after 63 days, recovered bullets were deformed or broken into multiple pieces but were not associated with adverse lesions. Ballistically delivered vaccines of both strains induced high immunological responses in cattle and bison confirmed by serological, immunological tests, PCR and pathomorphological examination of internal organs. Therefore, the clinical and ballistic characteristics of the modified Komarov's bullet, in addition to its ability to be delivered at distances of 100m, demonstrate its usefulness for use in remotely delivering brucellosis vaccines to free-ranging animals. A high immune response induced by ballistically delivered Brucella abortus 82 vaccine proves that this vaccine strain can be used for vaccination of free-ranging animals. PMID- 20362626 TI - The global introduction of inactivated polio vaccine can circumvent the oral polio vaccine paradox. AB - This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become transmissible circulating vaccine-derived polioviruses (cVDPVs), preventing use of the vaccine in the post-eradication era. This literature review identifies (1) risks of complete cessation of vaccination, (2) barriers and (3) solutions for the introduction of IPV in developing countries. The reviewed literature favours to circumvent the so-called "OPV paradox" by global introduction of IPV. PMID- 20362627 TI - Brucellosis in the United States: role and significance of wildlife reservoirs. AB - Regulatory programs for brucellosis in domestic livestock have been active in the U.S. for almost 80 years. Wildlife reservoirs of brucellosis include bison (Bison bison) and elk (Cervus elaphus nelsonii) for Brucella abortus whereas Brucella suis is the predominant species infecting feral swine. The persistence of brucellosis in wildlife reservoirs poses a risk for reintroduction of Brucella into domestic livestock. Reducing the prevalence of brucellosis in wildlife reservoirs is anticipated to be complicated and costly, and the problem is unlikely to be quickly resolved. Although some tools are currently available for use in the wildlife reservoirs, development of new vaccines, diagnostics, and management procedures will most likely be needed for effective control of brucellosis. PMID- 20362628 TI - The Rho GTPase activating CNF1 improves associative working memory for object-in place. AB - Cerebral Rho GTPases are crucially involved in cognitive abilities. This activity is thought to be related to the regulation of actin polymerization and, thereby, of the shape of the dendritic tree. Here we report that Cytotoxic Necrotizing Factor 1 (CNF1, 1fmol/kgicv), a bacterial protein endowed with Rho GTPase activating properties, enhances working memory for object location/discrimination in C57BL/6 mice. CNF1 selectively increased the exploration of a specific familiar object moved to a position that had been previously occupied by another familiar object. Conversely, the treatment left unaffected (i) exploration of a familiar object moved to a location that was previously unoccupied and (ii) exploration of a novel object. The effects were associated with changes in Rho GTPase status, since CNF1 C866S, a recombinant CNF1 in which the enzymatic activity was abolished through substitution of serine to cysteine at position 866, was ineffective in all the experiments. The study suggests that working memory for specific object-location associations critically depends on neural connectivity. It also confirms the therapeutic potential of the manipulation of Rho GTPase signaling in the modulation of memory processes. PMID- 20362629 TI - Increased prolyl endopeptidase activity in human neoplasia. AB - Prolyl endopeptidase (EC 3.4.21.26) (PEP) is a serine peptidase that converts several biologically active peptides. This enzyme has been linked to several neurological, digestive, cardiovascular and infectous disorders. However, little is known about its involvement in neoplastic processes. This study analyzes fluorimetrically cytosolic and membrane-bound PEP activity in a large series (n=122) of normal and neoplastic tissues from the kidney, colon, oral cavity, larynx, thyroid gland and testis. Cytosolic PEP activity significantly increased in clear cell renal cell carcinoma, urothelial carcinoma of the renal pelvis and head and neck squamous cell carcinoma. Both cytosolic and membrane-bound PEP activity were also increased in colorectal adenomatous polyps. These data suggest the involvement of PEP in some mechanisms that underlie neoplastic processes. PMID- 20362630 TI - alpha(9)beta(1) integrin engagement inhibits neutrophil spontaneous apoptosis: involvement of Bcl-2 family members. AB - Integrin signaling is comprised of well-characterized pathways generally involved in cell survival. alpha(9)beta(1) integrin has recently become a target of study and has been shown to present pro-survival effects on neutrophils. However, there are no detailed studies on how alpha(9)beta(1) integrin-coupled signaling pathways interact and how they converge to finally modulate spontaneous apoptosis in neutrophils. In this regard we sought to investigate the main signaling events triggered by alpha(9)beta(1) integrin engagement and how these signaling pathways modulate the apoptotic program of human neutrophils. Using VLO5, a snake venom disintegrin shown to bind to alpha(9)beta(1) integrin in neutrophils, we demonstrate that alpha(9)beta(1) integrin engagement leads to the activation of integrin signaling pathways and potently reduces neutrophil spontaneous apoptosis. These effects are dependent on the activation of PI3K and MAPK pathways, since both LY294002 (PI3K inhibitor) or PD95059 (MEK inhibitor) reverted the effects of VLO5/alpha(9)beta(1) interaction. Moreover we show that VLO5/alpha(9)beta(1) engagement induces NF-kappaB nuclear translocation and increases the ratio between anti- and pro-apoptotic proteins by inducing the degradation of pro-apoptotic protein Bad and increasing the expression of anti apoptotic protein Bcl-x(L). VLO5 also inhibited the early steps of neutrophil spontaneous apoptosis by preventing Bax translocation to the outer mitochondrial membrane and consequent cytochrome c release. In conclusion, as the mechanistic details of alpha(9)beta(1) integrin signaling pathways in human neutrophils becomes clearer, it should become possible to develop new therapeutic agents for human diseases where neutrophils play a prominent role. PMID- 20362631 TI - Identification of importin alpha1 as a novel constituent of RNA stress granules. AB - Importin alpha is a nuclear transport receptor well established for its ability to mediate importin beta-mediated nuclear import of proteins that possess classical nuclear localization signal (cNLS). Previously, we reported that importin alpha rapidly accumulates to the nucleus in response to H2O2-induced oxidative stress, which implies a role for this protein in stress response. In this study, we show that importin alpha1 (also known as KPNA2 or Rch1), a major subtype of the importin alpha family, localizes to RNA stress granules (SGs), large cytoplasmic bodies that are thought to function as RNA triage sites during stress response. The recruitment of importin alpha1 to SGs was compatible with its nuclear accumulation during heat shock. Depletion of endogenous importin alpha1 using siRNA showed that importin alpha1 regulates the dynamics of SG assembly, and that it promotes cell survival in arsenite-treated cells. These data revealed, for the first time, the involvement of importin alpha in the assembly of RNA granules and its pro-survival role during stress response. PMID- 20362632 TI - On the origin of cell functions encoded in the toponome. AB - The fluorescence imaging technology TIS enables the investigator to locate and decipher functional protein networks (the toponome) in a single cell or tissue section. TIS permits optical resolution and simultaneous detection of thousands of protein clusters in situ, composed of different protein species, and their visualization as coloured mosaic structures. Access to this level of protein organization relies on the ability of TIS to break the spectral limit of fluorescence microscopy and co-map a quasi unlimited number of different proteins by using specific tag libraries. The present review outlines the principles of the TIS technology as a fundamental approach to the internal structure, the code and the semantics of any protein system in situ. The review focusses on the discovery of basic coding rules in the toponome, indicating that cells establish functional protein networks on the cell surface by interlocking protein clusters, in which highly dissimilar proteins are topologically assembled (dissimilarity rule), and each cluster exhibits a characteristic geometry on the submicrometer to micrometer scale (geometry rule). The network is hierarchically controlled by a lead protein, whose inhibition leads to disassembly of the network and loss of function. Use of TIS on a proteome-wide scale provides a new way to medical systems biology. PMID- 20362633 TI - Soft X-ray holographic microscopy of chromosomes with high aspect ratio pinholes. AB - We used digital in-line soft X-ray holography (DIXH) in the Gabor geometry to image human chromosomes. The divergent wave front was generated by diffraction of synchrotron radiation from a high aspect ratio pinhole. As under our experimental conditions the achievable resolution depends on the pinhole radius, high aspect ratio holes with diameters in the 100 nm range were prepared by focused ion beam (FIB) milling. The central maximum of the obtained Airy pattern was used to image chromosomes prepared from metaphase HeLa cells at experimental resolutions of 370+/-40 nm with soft X-rays at 260 eV photon energy provided by the BESSY II synchrotron radiation facility. PMID- 20362634 TI - Susceptibility in vitro of Epstein-Barr Virus to myristoylated-peptide. AB - The anti-Epstein-Barr Virus (EBV) myristoylated-peptide (M.W. 916.2Da) is a natural product isolated from Heliothis virescens insect larval hemolymph (blood) that essentially has no cytotoxicity against human foreskin fibroblast cells. A (3 methyl only) version (M.W. 902.2 Da) of the structure was synthesized and tested for in vitro anti-EBV activity and cytotoxicity. The N-terminal end is lipophilic and used to get the compound across the cell membrane. The C-terminal end with its ring-shaped structures is likely used to inhibit DNA synthesis. The synthetic compound inhibited DNA synthesis/replication of EBV in Akata cells (B lymphocyte from Burkitt's lymphoma patient) in in vitro tissue culture. A DNA hybridization assay for anti-EBV activity using the Akata B-cell and two cytotoxicity assays using human foreskin fibroblast cells were done with the synthetic peptide. Effective concentration (EC90) at 20 microM inhibited viral replication by 90%. The EBV, known as Human Herpesvirus-4 (HHV-4) of the Herpesviridae family, has been described as a cancer-promoting double-stranded DNA virus that may also be involved in autoimmune disease. There are no antiviral drugs in clinical use for diseases caused by the EBV. PMID- 20362635 TI - Acute oral toxicity of N-acetyl-L-aspartic acid (NAA) in rats. PMID- 20362636 TI - Involvement of multiple molecular events in pyrogallol-induced hepatotoxicity and silymarin-mediated protection: evidence from gene expression profiles. AB - In this study, the involvement of various molecular events in pyrogallol-mediated hepatotoxicity was deciphered by differential mRNA transcription profiles of control and pyrogallol treated mice liver. The modulatory effects of silymarin on pyrogallol-induced differentially expressed transcripts were also looked into. Swiss albino mice were treated with or without pyrogallol. In some set of experiments, mice were also treated with silymarin 2 h prior to pyrogallol. Total RNA was isolated from liver and polyadenylated RNA was reverse-transcribed into Cye 3 or Cye 5 labelled cDNA. Equal amounts of labelled cDNA from two different groups were mixed and hybridized with mouse 15 k array. The hybridized arrays were scanned, analyzed and the expression level of each transcript was calculated. The differential expression was validated by quantitative real time polymerase chain reaction. Comparative transcription pattern showed an alteration in the expression of 183 transcripts (150 up-regulated and 33 down-regulated) associated with oxidative stress, cell cycle, cytoskeletal network, cell-cell adhesion, extra-cellular matrix, inflammation, apoptosis, cell-signaling and intermediary metabolism in pyrogallol-exposed liver and silymarin pre-treatment modulated the expression of many of these transcripts. Results obtained thus suggest that pyrogallol induces multiple molecular events leading to hepatotoxicity and silymarin effectively counteracts pyrogallol-mediated alterations. PMID- 20362637 TI - Placental transfer of melamine and its effects on rat dams and fetuses. AB - In 2008, an epidemic of cases of renal failure among Chinese infants, due to melamine contamination of milk, raised international concern. Thus, numerous studies on the metabolism of melamine were broadly undertaken. However, little is known about placental transfer of melamine. In this study, the possibility of placental transfer of melamine and its effects on fetuses and pregnant dams were determined. Melamine was respectively administered at 0, 40 and 400mg/kg body weight by daily gavage from gestation day (GD) 13 to GD 20 to control (C), low melamine (LM) and high melamine (HM) groups of pregnant female F344 rats. Rats were sacrificed 30min after the last gavage. Melamine was not detected in any of the control and placental samples, or in amniotic fluid from the LM group. Plasma and fetal melamine concentrations in the HM group were significantly higher than in the LM group (P<0.01). Liver enzyme determination revealed no differences among the three groups. However, plasma creatinine, plasma uric acid and blood urea nitrogen concentrations in dams were significantly increased by melamine (P<0.05). These results show that ingested melamine affects renal function in dams and dose-dependently passes the placental barrier to reach the fetus. PMID- 20362638 TI - The ameliorating effect of the extract of the flower of Prunella vulgaris var. lilacina on drug-induced memory impairments in mice. AB - Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and its flowers are used to treat inflammation in traditional Chinese medicine. In the present study, we studied the effects of the ethanolic extract of the flower of P. vulgaris var. lilacina (EEPV) on drug-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. EEPV (25 or 50 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (P<0.05). In the Morris water maze task, EEPV (25 mg/kg, p.o.) significantly shortened escape latencies in training-trials. Furthermore, swimming times within the target zone during the probe-trial were significantly increased as compared with scopolamine-treated mice (P<0.05). In addition, the reduced latency induced by MK-801 treatment in the passive avoidance task was ameliorated by EEPV (25 mg/kg, p.o.) (P<0.05). Additionally, the ameliorating effect of EEPV on scopolamine-induced memory dysfunction was antagonized by a sub effective dose of MK-801. These results suggest that EEPV would be useful for treating cognitive impairments induced by cholinergic dysfunction, and that it exerts its effects via NMDA receptor signaling. PMID- 20362639 TI - Spectrophotometric comparison of translucent composites and natural enamel. AB - OBJECTIVES: To compare the optical characters of four translucent composites and natural enamel. METHODS: Thirty natural enamel slabs and 120 composite replicas (n=30) using four brands of translucent composites (Polofil Supra, Brilliant Esthetic, Gradia Direct, and Vit-l-escence) were evaluated at the thicknesses of 1.0mm and 0.8mm. The colors of the enamel slabs or corresponding composite specimens placed on an A3 shade, white and black backgrounds were measured using a spectrophotometer. Color differences (DeltaE*) of the enamel-composite pairs and translucency parameter (TP) of each specimen were calculated. Reflection spectrums were recorded in the wavelength from 380nm to 780nm. Paired-t tests were performed to evaluate the differences of color coordinates (L*, a*, and b*) and TP values between the translucent composites and natural enamel. RESULTS: There were significant differences of color coordinates (L*, a*, and b*) between the enamel and translucent composites (P<0.05). Although no statistical difference of TP values were found in the enamel-composite pairs with Polofil Supra and Brilliant Esthetic composites. The main peaks of the reflectance spectrums of the enamel are different from the four brands of the translucent composites. A reddish shifting of the main reflection peaks was observed, while the thickness of the composite specimens decreasing from 1.0mm to 0.8mm. Whereas, the main reflection peak was not changed in the teeth enamel. CONCLUSIONS: The color and the translucency of translucent composites are different from the teeth enamel. PMID- 20362640 TI - Role of membrane sialic acid and glycophorin protein in thorium induced aggregation and hemolysis of human erythrocytes. AB - Thorium-232 ((232)Th), a natural radionuclide from the actinide family, is abundantly present in monazite and other ores. It is used as one of the prime fuel materials in nuclear industry and may pose an exposure risk to nuclear workers and members of the public. Human erythrocytes, as a classical cellular membrane model, were coincubated with (232)Th in order to elucidate whether this naturally occurring important radionuclide produced perturbations to cell membrane. Present study revealed that erythrocytes underwent aggregation or lysis depending on the ratio of (232)Th to cell. Scanning electron micrographs showed that erythrocytes transformed into equinocytes and/or spherocytes after (232)Th treatment. Further examination of erythrocyte by atomic force microscopy suggested significant increase in surface roughness after (232)Th treatment. Experiments on neuraminidase treated and/or anti-GpA antibody blocked erythrocytes suggested significant role of membrane sialic acid and glycophorin A (GpA) protein in aggregation or hemolytic effects of (232)Th. Further results showed that (232)Th caused hemolysis by colloid osmotic mechanism, as evidenced by potassium efflux, osmotic protection and osmotic fragility studies. Osmoprotection experiments indicated that hemolysis get elicited through the formation of membrane pores of approximately 2.0 nm in size. Hemolysis studies in presence of inhibitors (TEA, bumetanide, DIDS and amiloride) revealed the role of K(+) channel, Na(+)/K(+)/2Cl(-) channel, Cl(-)/HCO(3)(-) anion exchanger and Na(+)/H(+) antiporter in (232)Th induced erythrolysis. Presence of non-diffusible cation (N-methyl d-glucasamine) or anion (gluconate) in erythrocyte suspending medium further confirm the role of Na(+) and Cl(-) influx in hemolytic effect of (232)Th. These findings provide significant insight in structural, biochemical and osmotic toxic effects of (232)Th on human erythrocytes. PMID- 20362641 TI - Circulating CD33 and its clinical value in acute leukemia. AB - OBJECTIVE: CD33 is a cell surface antigen for committed myelomonocytic lineage. We explored the potential of detecting CD33 as cell-free circulating protein in patients with leukemia. MATERIALS AND METHODS: We developed a quantitative bead based immunoflow cytometry assay to measure cell-free circulating CD33 (cCD33) levels in the plasma of patients with acute leukemia, and correlated these results with corresponding clinical behavior. We measured cCD33 levels in the plasma of 48 healthy subjects and in patients with acute myelogenous leukemia (n = 98), acute lymphoblastic leukemia (n = 46), myelodysplastic syndrome (MDS) (n = 50), and myeloproliferative disorder (n = 49). RESULTS: Patients with acute myeloid leukemia and myeloproliferative disorders had significantly higher concentrations of cCD33 than the other patient groups and normal individuals (p = 0.0001), and among these groups, MDS patients displayed the lowest cCD33 levels (p = 0.02). Circulating CD33 values correlated positively with the CD33(+) blast cell counts in these patients. While there was no correlation between cCD33 levels and survival in acute myelogenous leukemia and MDS, higher cCD33 plasma concentrations did correlate with shorter survival in acute lymphoblastic leukemia (p = 0.03), and with shorter complete remission duration in acute myelogenous leukemia (p = 0.04) and MDS (p = 0.03). CONCLUSION: Circulating CD33 can be detected in the plasma from patients with leukemias, and cCD33 levels may have clinical implication, e.g., predictive and prognostic value, in these patients. PMID- 20362642 TI - Dopamine agonists increase perseverative instrumental responses but do not restore habit formation in a rat model of Parkinsonism. AB - Dopamine (DA) deafferentation of the dorsolateral striatum has been shown to prevent habit development, leaving instrumental behavior under action-outcome control that is persistently sensitive to modification of the motivational value of the reward. The present experiment further explored the basis of this dysfunction by examining the ability of intrastriatal DA agonist injections (D1 SKF 38393 or D2/D3 Quinpirole) during overtraining of a signaled instrumental task to restore habit formation in rats subjected to bilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. The results confirmed the impaired shift in performance from action to habit in control lesioned rats. However, lesioned rats repeatedly injected with quinpirole D2/D3 agonist showed an increase in non-rewarded instrumental responses (intertrials periods) during overtraining, suggesting the development of perseverative behavior. Following the procedure of devaluation, quinpirole D2/D3 agonist treatment, and to a lesser extent SKF 38393 D1 agonist, caused the persistence of sensitivity to reward devaluation, indicating clear goal-directed behavior despite extended training. This absence of restoration of habit formation by DA agonist treatment is discussed in the light of DA agonist effects in Parkinson patients. PMID- 20362643 TI - Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain. AB - To develop an effective neuroprotective strategy against ischemic injury, it is important to identify the key molecules involved in the progression of injury. Direct molecular analysis of tissue using mass spectrometry (MS) is a subject of much interest in the field of metabolomics. Most notably, imaging mass spectrometry (IMS) allows visualization of molecular distributions on the tissue surface. To understand lipid dynamics during ischemic injury, we performed IMS analysis on rat brain tissue sections with focal cerebral ischemia. Sprague Dawley rats were sacrificed at 24 h after middle cerebral artery occlusion, and brain sections were prepared. IMS analyses were conducted using matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) in positive ion mode. To determine the molecular structures, the detected ions were subjected to tandem MS. The intensity counts of the ion signals of m/z 798.5 and m/z 760.5 that are revealed to be a phosphatidylcholine, PC (16:0/18:1) are reduced in the area of focal cerebral ischemia as compared to the normal cerebral area. In contrast, the signal of m/z 496.3, identified as a lyso phosphatidylcholine, LPC (16:0), was clearly increased in the area of focal cerebral ischemia. In IMS analyses, changes of PC (16:0/18:1) and LPC (16:0) are observed beyond the border of the injured area. Together with previous reports- that PCs are hydrolyzed by phospholipase A(2) (PLA(2)) and produce LPCs,--our present results suggest that LPC (16:0) is generated during the injury process after cerebral ischemia, presumably via PLA(2) activation, and that PC (16:0/18:1) is one of its precursor molecules. PMID- 20362644 TI - Kainate-induced delayed onset of excitotoxicity with functional loss unrelated to the extent of neuronal damage in the in vitro spinal cord. AB - While excitotoxicity is a major contributor to the pathophysiology of acute spinal injury, its time course and the extent of cell damage in relation to locomotor network activity remain unclear. We used two in vitro models, that is, the rat isolated spinal cord and spinal organotypic cultures, to explore the basic characteristics of excitotoxicity caused by transient application of the glutamate analogue kainate followed by washout and analysis 24 h later. Electrophysiological records showed that fictive locomotion was slowed down by 10 microM kainate (with no histological loss) and fully abolished by 50 microM, while disinhibited bursting with unchanged periodicity persisted. Kainate concentrations (> or =50 microM) larger than those necessary to irreversible suppress fictive locomotion could still elicit dose-dependent motoneuron pool depolarization, and dose-dependent neuronal loss in the grey matter, especially evident in central and dorsal areas. Motoneuron numbers were largely decreased. A similar regional pattern was detected in organotypic slices, as extensive cell loss was dose related and affected motoneurons and premotoneurons: the number of dead neurons (already apparent 1 h after kainate) grew faster with the higher kainate concentration. The histological damage was accompanied by decreased MTT formazan production commensurate with the number of surviving cells. Our data suggest locomotor network function was very sensitive to excitotoxicity, even without observing extensive cell death. Excitotoxicity developed gradually leaving a time window in which neuroprotection might be attempted to preserve circuits still capable of expressing basic rhythmogenesis and reconfigure their function in terms of locomotor output. PMID- 20362646 TI - The effect of beta-naphthoflavone on the metabolism of amiodarone by hepatic and extra-hepatic microsomes. AB - Amiodarone is a potent antiarrhythmic drug with several limiting side effects, some of which have been correlated with increased levels of its more toxic metabolite, desethylamiodarone. Elevated serum desethylamiodarone to amiodarone ratios are associated with a risk of amiodarone-induced pulmonary toxicity. Polycyclic aromatic hydrocarbons such as beta-naphthoflavone are known to increase desethylamiodarone levels in rat in vivo. In this article we investigated if this increase was solely due to increased formation as a result of cytochrome P450 (CYP) 1A1 and 1A2 induction in different rat hepatic and extra hepatic tissues. Additionally, the effect of amiodarone treatment on CYP1A1 and 1A2 gene expression and activity was investigated. In rats, beta-naphthoflavone was found to increase desethylamiodarone forming activity in lung and kidney microsomes. Amiodarone increased beta-naphthoflavone mediated induction of CYP1A1 gene expression in liver, lung and kidney. However, there was no significant change in CYP1A activity. As expected, the data indicated that the increase in desethylamiodarone levels in vivo was partly due to increased formation through CYP1A1 induction, although increased formation was only evident in some extra hepatic tissues. Amiodarone treatment did not affect basal or induced CYP1A activity. PMID- 20362645 TI - Deletion of Puma protects hippocampal neurons in a model of severe status epilepticus. AB - Prolonged seizures (status epilepticus) can activate apoptosis-associated signaling pathways. The extent to which such pathways contribute to cell death might depend on the insult intensity, whereby the programmed or apoptotic cell death component is reduced when seizures are more severe or protracted. We recently showed that mice lacking the pro-apoptotic Bcl-2 homology domain 3-only protein Puma (Bbc3) were potently protected against damage caused by status epilepticus. In the present study we examined whether Puma deficiency was protective when the seizure episode was more severe. Intra-amygdala microinjection of 1 microg kainic acid (KA) into C57BL/6 mice triggered status epilepticus that lasted about twice as long as with 0.3 microg KA prior to lorazepam termination. Hippocampal damage was also significantly greater in the higher-dose group. Over 80% of degenerating neurons after seizures were positive for DNA fragmentation assessed by terminal deoxynucleotidyl dUTP nick end labeling (TUNEL). Microscopic analysis of neuronal nuclear morphology in TUNEL positive cells revealed the proportion displaying large rounded clumps of condensed chromatin was approximately 50% lower in the high-dose versus low-dose KA group. Nevertheless, compared to heterozygous and wild-type mice subject to status epilepticus by high-dose KA, neuronal death was reduced by approximately 50% in the hippocampus of Puma-deficient mice. These data suggest aspects of the apoptotic component of seizure-induced neuronal death are insult duration- or severity-dependent. Moreover, they provide further genetic evidence that seizure induced neuronal death is preventable by targeting so-called apoptosis-associated signaling pathways and Puma loss likely disrupts caspase-independent or non apoptotic seizure-induced neuronal death. PMID- 20362647 TI - Effects of prenatal diesel exhaust inhalation on pulmonary inflammation and development of specific immune responses. AB - There is increasing evidence that exposure to air pollutants during pregnancy can result in a number of deleterious effects including low birth weight and the incidence of allergic asthma. To investigate the in utero effects of DE exposure, timed pregnant BALB/c mice were exposed to 0, 0.8 or 3.1 mg/m(3) of DE during gestation days (GD) 9 to GD 18. The number of successful pregnancies was 15/20 in the air controls and 10/20 in each of the diesel exposures. Immune function in the 6-week-old offspring as determined by development of delayed type hypersensitivity (DTH) reactions to bovine serum albumin (BSA), antibody titers to injected sheep red blood cells (SRBC), splenic T cells expressing CD45(+)CD3(+)CD8(+) and CD3(+)CD25(+), and mRNA expression of TNF-alpha, TLR2, SP A, TGF-beta and Foxp3 in the lung were not affected by prenatal DE exposure. On the other hand, lung TLR4 mRNA expression, the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and splenic T cells expressing CD45(+)CD3(+)CD4(+) and CD4(+)CD25(+) were differentially affected depending on the DE concentration and gender. When additional groups of mice were sensitized and challenged via the respiratory tract with ovalbumin to induce allergic airway inflammation, female mice had higher protein levels in the BALF compared to males and this was reduced by prenatal exposure to either concentration of DE. No other changes in allergen-induced immunity, lung function or severity of inflammation were noted. Collectively, the results show that in utero exposure to DE altered some baseline inflammatory indices in the lung in a gender-specific manner, but had no effect on development of specific immune responses to experimental antigens, or the severity of allergic lung inflammation. PMID- 20362648 TI - Sensory and pulmonary effects of acute exposure to sulfur dioxide (SO2). AB - BACKGROUND: Exposure to sulfur dioxide (SO(2)) affects large populations worldwide. Pulmonary effects have been reported at concentrations relevant in the general (<0.5 ppm) and working environment (>0.5 ppm). SO(2) is an irritant but the existing studies often emphasize only pulmonary effects and no clear dose response relationship has yet been described. OBJECTIVES: Using a multi-level, multi-method approach, odor annoyance, sensory irritation and pulmonary effects of SO(2) were to be investigated in an experimental exposure study. METHODS: Eye blink frequency, rhinomanometry, spirometry and symptom ratings of acute health effects were assessed before, during, and after the exposures. Each session lasted 4h and concentrations of 0.5, 1, and 2 ppm were investigated and compared to a control condition using clean air. Sixteen human volunteers (8 females/8 males) participated and during exposure light physical exercise was simulated with bicycle ergometry. RESULTS: Eye blink frequency, nasal airflow, and lung function were not affected by the acute SO(2) exposure investigated. These physiological responses to moderate SO(2) exposures were not significantly affected by gender. Regarding subjectively measured chemosensory sensations, only odor annoyance ratings increased in a dose-dependent manner, but the average magnitudes were labeled weak to moderate. CONCLUSIONS: In healthy volunteers, without hyperresponsiveness to SO(2), no dose-dependent effects of acute SO(2) exposures up to 2 ppm could be measured. Due to olfactory perceptions subjects were aware of the different SO(2) exposures but the associated annoyance was relatively low. PMID- 20362649 TI - Serum proteomic profiling analysis of chronic arsenic exposure by using SELDI-TOF MS technology. AB - This study was to investigate the differences in serum proteomic profiling among subjects exposed to different levels of arsenic in drinking water and to identify proteins related to arsenicosis. A total of 148 subjects from endemic regions of China were selected and divided into low (0-8.30 microg/L), medium (16.30-37.60 microg/L) and high (140.88-273.67 microg/L) exposure groups. High exposure group consisted of subjects with and without skin lesions. Serum proteomic profiling was analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. Twenty proteins were found significantly different among three groups. Further multivariate logistic regression revealed that no different proteins existed in medium versus low exposure group. A panel of five proteins, including m/z of 15167.7, 7783.1, 7580.7, 2952.6 and 2237.4, was seen in high versus low exposure group, with a sensitivity of 93.0% and specificity of 87.5%. The same panel was found in high versus a combination of low and medium exposure groups but with somewhat lower predicting power. Only one protein was significantly different between high exposure group with and without skin lesions. The results indicate that high levels of arsenic exposure could significantly change human serum proteomic profiling, which can be detected before skin lesions occur. PMID- 20362651 TI - Assessment of candidate biomarkers of drug-induced hepatobiliary injury in preclinical toxicity studies. AB - This study was designed to assess the value of a set of potential markers for improved detection of liver injury in preclinical toxicity studies. Male Wistar rats were treated with drug candidates (BAY16, EMD335823, BI-3) that previously failed during development, in part due to hepatotoxicity, at two dose levels for 1, 3 and 14 days. Concentrations of lipocalin-2/NGAL and clusterin, which are frequently overexpressed and released from damaged tissues, and thiostatin, recently identified within PredTox as being elevated in urine in response to liver injury, were determined in rat urine and serum by ELISA. This was supplemented by confirmatory qRT-PCR and immunohistochemical analyses in the target organ. Serum paraoxonase-1 activity (PON1), which has been suggested as a marker of hepatotoxicity, was determined using a fluorometric assay. Clusterin and PON1 were not consistently altered in response to liver injury. In contrast, thiostatin and NGAL were increased in serum and urine of treated animals in a time- and dose-dependent manner. These changes correlated well with mRNA expression in the target organ and generally reflected the onset and degree of drug-induced liver injury. Receiver-operating characteristics (ROC) analyses supported serum thiostatin, but not NGAL, as a better indicator of drug-induced hepatobiliary injury than conventional clinical chemistry parameters, i.e. ALP, ALT and AST. Although thiostatin, an acute phase protein expressed in a range of tissues, may not be specific for liver injury, our results indicate that thiostatin may serve as a sensitive, minimally-invasive diagnostic marker of inflammation and tissue damage in preclinical safety assessment. PMID- 20362650 TI - Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. AB - To understand the underlying mechanism for apoptosis induced by titanium dioxide nanoparticles (TNP), human airway epithelial cell line was cultured to investigate the relevant apoptosis pathways. Our results showed that the levels of reactive oxygen species and morphological apoptosis increased in a dose dependent manner whereas cell viability decreased in a similar manner in response to TNP exposure in the BEAS-2B cells. The activities of caspase 3 and PARP were also increased in parallel to the morphological apoptosis. Levels of caspase 9 increased significantly whereas there were no detectable changes in caspase 8 and t-Bid in the TNP treated cells. Caspase 9 inhibition blocked the TNP-induced activation of caspase 3 significantly. The levels of bax, cytochrome C, p53 and bcl-2 also changed reflecting the activation of intrinsic apoptosis pathway. Our results provide solid evidence that apoptosis in BEAS-2B cells exposed to TNP occurred via a mitochondrial apoptosis pathway independent of caspase 8/t-Bid pathway. PMID- 20362652 TI - Sustained release of ATP encapsulated in chitosan oligosaccharide nanoparticles. AB - The chemical cross-linked chitosan oligosaccharide (CSO) nanoparticles containing ATP/CSO ionic complex nano-components were prepared using combination techniques of W/O miniemulsion, chemical cross-linking and ionic complexation. The resulted nanoparticles had about 110 nm diameter and 20 mV surface zeta potential. The ATP loading efficiencies in nanoparticles could reach up to 40.6-69.5%. It was found that the ATP loading efficiency increased with increasing the amount and the molecular weight of chitosan oligosaccharide, and decreased with increasing molar ratio of glutaraldehyde to chitosan oligosaccharide. In vitro ATP release from chemical cross-linked CSO nanoparticles could continue for 24h, and could also be adjusted by the amount and molecular weight of CSO, and the molar ratio of glutaraldehyde to CSO. The higher molecular weight and smaller amount of CSO, and the lower molar ratio of glutaraldehyde to CSO led the slower ATP release rate. Furthermore, it was also found that the CSO nanoparticles could be uptaken by HepG-2 tumor cells, and could be applied for intracellular drug delivery. PMID- 20362653 TI - In vitro skin permeation of monoolein nanoparticles containing hydroxypropyl beta cyclodextrin/minoxidil complex. AB - Monoolein (MO) cubic phases entrapping hydroxypropyl beta-cyclodextrin (HPbetaCD)/minoxidil (MXD) complex were prepared by hydrating molten MO with the complex solution, where the concentrations of HPbetaCD/MXD were 1.0%/0.32% 19.4%/1.98%. Without HPbetaCD, the maximum content of MXD loaded in the cubic phase was only 0.071%, but with aid of HPbetaCD, the content in the cubic phase increased up to 5.72%. The nanoparticles of the cubic phase were prepared by a bath type sonication using a Pluronic F127 as a dispersant. HPbetaCD/MXD complex had little effect on the size and the structure of cubic phase nanoparticles. In vitro skin permeation of MXD loaded in the cubic phase nanoparticles (2.44 mg/cm(2) for 18 h), were higher than that of MXD dissolved in propylene glycol/water/ethanol (20/30/50, v/v/v) (1.91 mg/cm(2) for 18 h), but the amount of MXD remained within skin was higher with the MXD solution (0.068 mg/cm(2) for 18 h) than with the nanoparticles (0.023 mg/cm(2) for 18 h). PMID- 20362654 TI - Hepatoprotective effects of Rubus aleaefolius Poir. and identification of its active constituents. AB - The purpose of this study was to study the hepatoprotective effects of the most promising extract of the root from Rubus aleaefolius Poir. and to isolate and identify the active components. Various crude forms of Rubus aleaefolius have been evaluated for their effects on CCl(4)-induced acute liver injury in mice vivo experimental model. Treatment groups contained 5 sub-groups that were ethanol crude extract; the high/low dosage ethyl acetate or n-butanol fraction; extracted with ethyl acetate or n-butanol after the residues and major constituent; intragastrically administrated with 35 mg/kg; 35, 4.6 mg/kg; 35, 5.8 mg/kg; 35 mg/kg and 3.5 mg/kg for 7 days. The serum samples were collected for biological analysis and also carried out histopathological studies. The low dosage ethyl acetate fraction was the most active when the fractions were compared. It was found to decrease AST, ALT; to prevent formation of hepatic MDA, NO and intensify the activity of SOD. The histopathological changes induced by CCl(4) were also significantly reduced. The separation revealed the presence of six constituents by a bioassay-guided fractionation, beta-Sitosterol (1), 1beta Hydroxyeuscaphic acid (2), Oleanolic acid (3), Myrianthic acid (4), Euscaphic acid (5), and Tomentic acid (6). Among them, compounds 2, 4, 5 in Rubus aleaefolius root is reported here for the first time. 1beta-Hydroxyeuscaphic acid (major constituent) showed a tremendous activity and the results confirm the traditional uses of Rubus aleaefolius in treating hepatitis. PMID- 20362655 TI - Protection of centrilobular necrosis by Curcuma comosa Roxb. in carbon tetrachloride-induced mice liver injury. AB - AIM OF THE STUDY: To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl(4)-induced liver injury in adult male mice. MATERIALS AND METHODS: Hepatotoxicity was induced by an intraperitoneal injection of CCl(4) and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl(4) administration and the protection from liver injury was assessed. RESULTS: CCl(4)-induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12-24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S transferase (GST). CONCLUSION: Curcuma comosa has a potent protective property against CCl(4)-induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity. PMID- 20362656 TI - KIOM-79 prevents methyglyoxal-induced retinal pericyte apoptosis in vitro and in vivo. AB - AIMS OF STUDY: The purpose of this study was to investigate the protective effects of KIOM-79, a combination of four plant extracts, on retinal pericytes loss, which is one of the histopathological hallmarks of early diabetic retinopathy. MATERIALS AND METHODS: To investigate the protective effect of KIOM 79 on pericyte apoptosis, we have used methylglyoxal (MGO)-treated primary rat retinal pericytes and retinal vessels from intravitreally MGO-injected eyes. Primary rat retinal pericytes were exposed to 400 microM MGO for 6h with or without KIOM-79. 400 microM final intravitreal concentration of MGO with or without KIOM-79 (10 microg/ml final intravitreal concentration) were intravitreally injected into the right eyes of rats for 2 days. The left eyes were received 3mul of saline only. Retinal vessels were then isolated. We examined apoptosis, ROS productions, 8-OHdG in cultured rat retinal pericytes and retinal vessels. RESULTS: In CCK-8 assay and TUNEL staining, MGO-induced apoptosis of rat retinal pericytes was markedly inhibited by KIOM-79. KIOM-79 significantly reduced intracellular ROS productions and oxidative damage induced by MGO. In addition, the intravitreal injection of KIOM-79 prevented apoptosis of retinal microvascular cells, MGO accumulation and oxidative DNA damage in intravitreally MGO-injected eye. CONCLUSION: These observations suggest that KIOM 79 acts through an antioxidant mechanism to protect against oxidative stress induced apoptosis in retinal pericytes. PMID- 20362657 TI - Debottlenecking the 1,3-propanediol pathway by metabolic engineering. AB - The history of 1,3-propanediol (1,3-PD) conversion from being a specialty chemical to being a bulk chemical illustrates that the concerted effort of different metabolic engineering approaches brings the most successful results. In order to metabolically tailor the 1,3-PD production pathway multiple strategies have been pursued. Knocking-out genes responsible for by-products formation, intergeneric transfer and overexpression of the genes directly involved in the pathway, manipulation with internal redox balance, introduction of a synthetic flux control point, and modification of the substrate mechanism of transport are some of the strategies applied. The metabolic engineering of the microbial 1,3-PD production exploits both native producers and microorganisms with acquired ability to produce the diol via genetic manipulations. Combination of the appropriate genes from homologous and heterologous hosts is expected to bring a desired objective of production of 1,3-PD cheaply, efficiently and independently from non-renewable resources. The state-of-the-art of the 1,3-PD pathway metabolic engineering is reviewed in this paper. PMID- 20362658 TI - Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by beta-amyloid peptides 25-35 in PC12 cells. AB - OBJECTIVE: Genistein (GEN), a principal component of soybean isoflavones, might possess the neuroprotective role through its antioxidant activity. However, the detailed mechanisms are unknown yet. The purpose of this study was to investigate whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25 35 (Abeta25-35) in PC12 cells. METHODS: The PC12 cells were pre-incubated with or without GEN for 2h following incubation with Abeta25-35 for another 24h. MTT was used to assess the cell viability. Hoechst 33342 staining was applied to determine the apoptotic cells. Confocal laser scanning microscopy was implemented to examine the reactive oxygen species (ROS) levels. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Reduced and oxidized glutathione (GSH/GSSG) ratio was analyzed by using assay kits. Western blot analysis was performed to assess the proteins expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS). RESULTS: GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25 35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1. CONCLUSION: GEN could alleviate the oxidative stress caused by Abeta25-35 treatment and maintain redox balance in PC12 cells, which might be associated with the regulation of Nrf2/HO-1 signal pathway. PMID- 20362659 TI - Assessment of cytocompatibility of surface-modified CdSe/ZnSe quantum dots for BALB/3T3 fibroblast cells. AB - With the widespread use of quantum dots (QDs), the likelihood of exposure to QDs has been assumed to have increased substantially. Recently, QDs have been employed in numerous biological and medical applications. However, there is a lack of toxicological data pertaining to QDs. In this study, we aimed to investigate the cytocompatibility of surface-modified CdSe/ZnSe QDs for BALB/3T3 fibroblast cells. The ligands used for surface modification are mercaptopropionic acid (MPA) and Gum arabic (GA)/tri-n-octylphosphine oxide (TOPO). Cells were exposed to different concentrations of QDs followed by illustrative cytotoxicity analyses. Furthermore, we used a confocal microscope to assess intracellular uptake of QDs. Confocal images showed that MPA-coated QDs were distributed inside the cytoplasmic region of cells. In contrast, GA/TOPO-coated QDs were not found inside cells. MPA-coated QDs were highly cytocompatible, whereas GA/TOPO-coated QDs were toxic to the cells. Cells treated with GA/TOPO-coated QDs showed altered morphology, decreased viability, significant concentrations of intracellular free cadmium, detectable reactive oxygen species (ROS) formation, depolymerized cytoskeleton, and irregular-shaped nuclei. This study suggests that surface modification by ligands plays a significant role in the prevention of cytotoxicity of QDs. PMID- 20362660 TI - In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain. AB - Carbamazepine (CBZ), phenytoin (PHT), and gabapentine (GBP) are classical antiepileptic drugs (AEDs) that act through a variety of mechanisms. We have tested the in vitro effects of CBZ, PHT, and GBP at different concentrations on ectonucleotidase and acetylcholinesterase activities in zebrafish brain. CBZ inhibited ATP hydrolysis at 1000 microM (32%) whereas acetylcholine hydrolysis decreased at 500 microM (25.2%) and 1000 microM (38.7%). PHT increased AMP hydrolysis both at 500 microM (65%) and 1000 microM (64.8%). GBP did not promote any significant changes on ectonucleotidase and acetylcholinesterase activities. These results have shown that CBZ can reduce NTPDase (nucleoside triphosphate diphosphohydrolase) and PHT enhance ecto 5'-nucleotidase activities. Therefore, it is possible to suggest that the AEDs induced-effects on ectonucleotidases are related to enzyme anchorage form. Our findings have also shown that high CBZ concentrations inhibit acetylcholinesterase activity, which can induce an increase of acetylcholine levels. Taken together, these results showed a complex interaction among AEDs, purinergic, and cholinergic systems, providing a better understanding of the AEDs pharmacodynamics. PMID- 20362662 TI - Synchrotron FTIR micro-spectroscopy study of the rat hippocampal formation after pilocarpine-evoked seizures. AB - In the present work, synchrotron radiation Fourier transform infrared (SRFTIR) micro-spectroscopy and imaging were used for topographic and semi-quantitative biochemical analysis of rat brain tissue in cases of pilocarpine-induced epilepsy. The tissue samples were analyzed with a beam defined by small apertures and spatial resolution steps of 10 microm which allowed us to probe the selected cellular layers of hippocampal formation. Raster scanning of the samples has generated 2D chemical cartographies revealing the distribution of proteins, lipids and nucleic acids. Spectral analysis has shown changes in the saturation level of phospholipids and relative secondary structure of proteins. Special interest was put in the analysis of two areas of the hippocampal formation (sector 3 of the Ammon's horn, CA3 and dentate gyrus, DG) in which elemental abnormalities were observed during our previous studies. Statistically significant increase in the saturation level of phospholipids (increased ratio of the absorption intensities at around 2921 and 2958 cm(-1)) as well as conformational changes of proteins (beta-type structure discrepancies as shown by the increased ratio of the absorbance intensities at around 1631 and 1657 cm(-1) as well as the ratio of the absorbance at 1548 and 1657 cm(-1)) were detected in pyramidal cells of CA3 area as well as in the multiform and molecular layers of DG. The findings presented here suggest that abnormalities in the protein secondary structure and increases in the level of phospholipid saturation could be involved in mechanisms of neurodegenerative changes following the oxidative stress evoked in brain areas affected by pilocarpine-induced seizures. PMID- 20362661 TI - Synergism between immunostimulation and prevention of surgery-induced immune suppression: an approach to reduce post-operative tumor progression. AB - BACKGROUND: A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that integration of peri-operative immunostimulation and blockade of immunosuppression could synergistically improve post-operative anti-metastatic immunity and long-term survival. METHODS: Two syngeneic tumor models in F344 rats were employed, studying post-operative tumor progression. In the first model, survival following laparotomy and CRNK-16 leukemia was studied. Rats were peri-operatively treated with the immuno stimulant poly I-C (5x0.2 mg/kg/inj), with catecholamine- and prostaglandin blockers (shown to prevent post-operative immunosuppression: 4.5 mg/kg nadolol, 4 mg/kg indomethacin), with both interventions, or with neither. Long-term survival was assessed thereafter. The second model used the MADB106 mammary adenocarcinoma, assessing its lung tumor retention (LTR) following i.v. inoculation, as well as host marginating-pulmonary NK numbers and activity against this tumor. IL-12 was employed for immunostimulation (4x1.5 microg/kg/inj), with and without the above blockers. RESULTS: Post-operative CRNK 16 survival rates were significantly improved only by the integrated approach of immune stimulation and endocrine blockers. Post-operative MADB106 LTR was additively reduced by the two interventions. Importantly, while IL-12 increased pulmonary NK cytotoxicity against MADB106, surgery markedly suppressed this cytotoxicity in both IL-12 and vehicle treated animals. The blockers prevented this suppression per lung and per single NK cell. CONCLUSIONS: Immunostimulation could be rendered ineffective post-operatively due to immunosuppression; therefore integrating endocrine-blocker therapies into the realm of peri operative immunotherapy could optimize immune control over residual disease, potentially improving clinical outcomes. PMID- 20362663 TI - Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type I diabetic rats. AB - We previously showed that xanthine oxidase activity increases in type I diabetic animals and that this is a significant cause of the oxidative stress which occurs in the disease. The aim of this work was to search for molecular links between xanthine oxidase-induced oxidative stress and inflammation in Type I diabetes and to assess the ability of allopurinol, a drug widely used in clinical practice, to prevent both processes. 3-month-old male Wistar rats were made diabetic by injection (i.p.) of either streptozotocin or alloxan. Allopurinol (32 mg/Kg) was administered (i.p) to diabetic rats after they had shown clear signs of diabetes such as glucosuria and polyuria. Hepatic phospho-IKKbeta and phospho-IkappaBalpha contents were increased in diabetic animals. This was accompanied by increased levels of NF-kappaB (p65 protein content) in liver nuclear extracts. Hepatic expression of NF-kappaB dependent inflammatory cytokines and enzymes, namely interleukin 1beta, iNOS and interleukin 6 were markedly increased. Both diabetes induced activation of NF-kappaB signalling cascade and subsequent over expression of inflammatory cytokines and enzymes were abolished by administration of allopurinol. Moreover, we found a significant neutrophil infiltration in the liver of diabetic animals. These events were also prevented by administration of allopurinol. PMID- 20362664 TI - RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy. AB - The chronic stimulation of certain G protein-coupled receptors promotes cardiomyocyte hypertrophy and thus plays a pivotal role in the development of human heart failure. The beta-adrenergic receptors (beta-AR) are unique among these in that they signal via Gs, whereas others, such as the alpha1-adrenergic (alpha1-AR) and endothelin-1 (ET-1) receptors, predominantly act through Gq. In this study, we investigated the potential role of regulator of G protein signalling 2 (RGS2) in modulating the hypertrophic effects of the beta-AR agonist isoproterenol (ISO) in rat neonatal ventricular cardiomyocytes. We found that ISO induced hypertrophy in rat neonatal ventricular myocytes was accompanied by the selective upregulation of RGS2 mRNA, with little or no change in RGS1, RGS3, RGS4 or RGS5. The adenylyl cyclase activator forskolin had a similar effect suggesting that it was mediated through cAMP production. To study the role of RGS2 upregulation in beta-AR-dependent hypertrophy, cardiomyocytes were infected with adenovirus encoding RGS2 and assayed for cell growth, markers of hypertrophy, and beta-AR signalling. ISO-induced increases in cell surface area were virtually eliminated by the overexpression of RGS2, as were increases in alpha-skeletal actin and atrial natriuretic peptide. RGS2 overexpression also significantly attenuated ISO-induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt activation, which may account for, or contribute to, its observed antihypertrophic effects. In contrast, RGS2 overexpression significantly activated JNK MAP kinase, while decreasing the potency but not the maximal effect of ISO on cAMP accumulation. In conclusion, the present results suggest that RGS2 negatively regulates hypertrophy induced by beta-AR activation and thus may play a protective role in cardiac hypertrophy. PMID- 20362665 TI - RasV12 induces Survivin/AuroraB pathway conferring tumor cell apoptosis resistance. AB - Several cancers are treated by interferons alpha and gamma in association with conventional chemotherapy due to the resistance observed with interferon treatment alone. The frequency of un-sensitive cancer depends on tumor origin and oncogenic genes. Preclinical studies have highlighted interferon resistance in many cancers such as colon carcinoma due to oncogenic Ras. However, the resistance mechanism remains elusive. Apoptosis and proliferation of Ras(wt) and mutated Ras(V12) transformed colon carcinoma cells treated with several recombinant interferon combinations were analyzed by flow cytometer and immunoblot. Apoptotic pathways of resistant Ras(V12) cells were investigated using siRNA strategy to determine key proteins involved in this process. We show that interferons alpha and gamma synergized to induce human Ras(wt) colon carcinoma cell (HT29) apoptosis by caspases and PARP-1 cleavages in contrast to Ras(V12) mutated colon carcinoma cells (SW480, HT29 clone). However, Ras(V12) siRNA restored interferon sensitivity of Ras(V12)-HT29 clone to apoptosis. Survivin siRNA increased interferon apoptosis in Ras(wt) cells demonstrating the key role of this protein in cell survival. Ras(V12) mutation in HT29 clone neutralized the interferon effect on Survivin suppression and maintained high level of phospho-Aurora-B/Histone H3, which protected cells from apoptosis. SiRNA strategy against both Aurora-B and Survivin in Ras(V12) cells synergized to restore interferon -induced apoptosis. Ras(V12) cells are less sensitive than Ras(wt) cells to interferon induced cell apoptosis due to a Survivin/Aurora-B survival alternative pathway. Taken together, these results may provide interest in siRNA-therapeutic strategy and diagnostic relevance for therapy. PMID- 20362666 TI - Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients. AB - Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and catalyses the ring opening of 5,6-dihydrouracil and 5,6 dihydrothymine. To date, only 11 individuals have been reported suffering from a complete DHP deficiency. Here, we report on the clinical, biochemical and molecular findings of 17 newly identified DHP deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological and gastrointestinal abnormalities and markedly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in plasma, cerebrospinal fluid and urine. Analysis of DPYS, encoding DHP, showed nine missense mutations, two nonsense mutations, two deletions and one splice-site mutation. Seventy-one percent of the mutations were located at exons 5-8, representing 41% of the coding sequence. Heterologous expression of 11 mutant enzymes in Escherichia coli showed that all but two missense mutations yielded mutant DHP proteins without significant activity. Only DHP enzymes containing the mutations p.R302Q and p.T343A possessed a residual activity of 3.9% and 49%, respectively. The crystal structure of human DHP indicated that the point mutations p.R490C, p.R302Q and p.V364M affect the oligomerization of the enzyme. In contrast, p.M70T, p.D81G, p.L337P and p.T343A affect regions near the di-zinc centre and the substrate binding site. The p.S379R and p.L7V mutations were likely to cause structural destabilization and protein misfolding. Four mutations were identified in multiple unrelated DHP patients, indicating that DHP deficiency may be more common than anticipated. PMID- 20362667 TI - Mutations in N-cadherin and a Stardust homolog, Nagie oko, affect cell-cycle exit in zebrafish retina. AB - It has been reported that the loss of apicobasal cell polarity and the disruption of adherens junctions induce hyperplasia in the mouse developing brain. However, it is not fully understood whether hyperplasia is caused by an enhanced cell proliferation, an inhibited neurogenesis, or both. In this study, we found that the ratio of the number of proliferating progenitor cells to the total number of retinal cells increases in the neurogenic stages in zebrafish n-cadherin (ncad) and nagie oko (nok) mutants, in which the apicobasal cell polarity and adherens junctions in the retinal epithelium are disrupted. The cell-cycle progression was not altered in the ncad and nok mutants. Rather, the ratio of the number of cells undergoing neurogenic cell division to the total number of cells undergoing mitosis decreased in the ncad and nok mutant retinas, suggesting that the switching from proliferative cell division to neurogenic cell division was compromised in these mutant retinas. These findings suggest that the inhibition of neurogenesis is a primary defect that causes hyperplasia in the ncad and nok mutant retinas. The Hedgehog-protein kinase A signaling pathway and the Notch signaling pathway regulate retinal neurogenesis in zebrafish. We found that both signaling pathways are involved in the generation of neurogenic defects in the ncad and nok mutant retinas. Taken together, these findings suggest that apicobasal cell polarity and epithelial integrity are essential for retinal neurogenesis in zebrafish. PMID- 20362668 TI - Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24 hydroxylase in the human kidney and renal clear cell cancer. AB - BACKGROUND: The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal the segmental location of expression, and clarify whether the reported loss of VDR in CCc is coincident with alterations of vitamin D metabolism. MATERIALS AND METHODS: Tissue was obtained from nine patients (eight CCc and one atrophic kidney), mRNAs were detected with RT-PCR and in situ hybridisation (ISH), and expression of proteins determined by immunohistochemistry and western blotting. RESULTS: We detected expression of VDR and the vitamin D metabolising enzymes in normal kidney. VDR and CYP27B1 were strongly expressed in proximal tubules, while CYP2R1 and CYP27A1 had a marked expression in distal tubules. In CCc expression was lost for VDR and all the enzymes, except for very few cells expressing all the investigated proteins. CONCLUSION: This study shows that VDR and all the vitamin D metabolising enzymes are expressed in the normal kidney. During the malignant transformation to CCc, expression of VDR and the metabolising enzymes is lost, however the implications of this loss are unknown. PMID- 20362669 TI - Effect of the supplementation of dietary rich phytoestrogens in altering the vitamin D levels in diet induced osteoporotic rat model. AB - Plant-derived estrogen-like compounds such as isoflavones (IF) especially daidzein and genistein are said to be preserving the bone in the osteoporotic conditions. However, it is not known whether a combination of IF and calcium (Ca) supplementation attenuates losses in bone mass and prevents the loss of vitamin D (VD). The present study addresses the role of phytoestrogens (PE) and Ca supplementation in low Ca and low VD diet induced osteoporosis (OSP). Cowpea (CP) which has high amount of the IF was selected to study its effect on diet induced osteoporotic conditions. Female weanling WNIN rats (total of 68) were divided into five groups and fed for five weeks on semisynthetic diet with low Ca (0.15%) and low VD (0.1IU/day/rat) in combination with low (10 mg/kg) or high (25 mg/kg) concentrations of PEs derived from CPIF. The study groups are: (I) normal Ca(0.47%) and normal VD (25IU/day/rat), (II) low Ca+low VD, (III) low Ca+low VD+low CPIF (10 mg/kg diet), (IV) low Ca+low VD+high CPIF (25 mg/kg diet) and (V) low Ca+low VD+17-(-estradiol (3.2 mg/kg diet). After the development of OSP the group II was subgrouped into: (SG I) continued on low Ca+VD, (SG II) low CPIF, (SG III) high CPIF, (SG IV) 17-beta-estradiol and (SG V) normal Ca and VD. Serum 25-VD levels were in the range of 14-38 ng/ml in groups I, III, IV and V, where as the values were very low in the group II (5.8 ng/ml). These were partially reversed upon supplementation of CPIF. The results correlated with altered Ca levels, body weight, bone mineral density and content and other related biochemical parameters. The paper further explains the possibility of protective and therapeutic role of VD in the presence of CPIF in osteoporotic health manifestations. PMID- 20362670 TI - The 1,25-dihydroxyvitamin D3-independent actions of the vitamin D receptor in skin. AB - The vitamin D endocrine system plays important but poorly understood roles in the skin and in hair follicle cycling. Rare, human genetic disorders and knockout mouse models highlight essential roles and potentially novel mechanisms of the vitamin D endocrine system in the skin. Vitamin D receptor knockout mice express a hair follicle cycling defect and a hyperproliferative phenotype resulting in disordered skin structure, epidermal thickening, and alopecia. In contrast, ligand knockout mice (i.e., mice with a disrupted CYP27B1 gene that encodes the 25-hydroxyvitamin-D3 1alpha-hydroxylase) have normal hair follicle function and a comparatively modest skin phenotype. These disparate models indicate that VDR may function independently of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in regulating hair follicle cycling and skin biology. Recent studies highlight this concept and provide key support for this hypothesis. While VDR knockout mice are highly susceptible to chemically induced skin tumorigenesis, CYP27B1 knockouts are resistant. These studies reveal a second global physiological process in the skin that may be regulated by VDR in a 1,25(OH)2D3-independent fashion, namely, genoprotection against carcinogenic mutagens. Key cellular and molecular data supporting this mechanism were published recently showing a keratinocyte selective transactivation activity mediated by VDR that is independent of the 1,25(OH)2D3 ligand. Thus, evidence is building to support a potentially novel, 1,25(OH)2D3-independent mechanism through which VDR functions in keratinocytes and perhaps within stem cell populations in the follicle to regulate genoprotection and other key developmental processes in the skin. PMID- 20362671 TI - Stereoselective synthesis of C24-hydroxylated vitamin D3 analogs: a practical and expeditius route to calcipotriol. AB - The synthesis of the clinically important drug calcipotriol (2, MC903) is described as an example of a new and efficient approach to C24-hydroxylated analogs and metabolites of vitamin D3 (1). The key step of the process is the generation of the C24 stereocenter by DAIB [(-)-3-exo-(dimethylamino)isoborneol] catalyzed addition of the alkenylzinc derivative of alkyne 3 to cyclopropylcarboxaldehyde. PMID- 20362672 TI - Vascularized whole thymus transplantation in Rowett nude rats: effect of thymus allograft volume on tolerance induction. AB - Thymus transplantation enables recipient T cells to develop and mature within the donor thymus and achieve donor-specific transplantation tolerance. The relationship between the volume of the vascularized graft and the extent of tolerance induced to it remains unclear and needs further investigation. Adult male Fischer and Rowett nude rats (8-10 weeks old, 200-250 g) were used as donors and recipients of allogeneic thymus grafts. Rowett nude rats were randomly divided into three groups: Group A, sham-grafted controls (n=5); Group B, recipients of whole thymus (including two thymic lobes) (n=10); Group C, recipients of one thymic lobe (n=8). The animal body weight and survival were monitored postoperatively. Histological examination was used to monitor graft survival. Graft function and tolerance induction were assessed by mixed lymphocyte reaction (MLR), flow cytometry (FCM), and full-thickness skin graft studies. All animals survived. After 16 weeks, the vessels supplying blood to the thymus graft were patent and histologically the grafts had normal corticomedullary architecture. Body weight increased to the greatest extent in Group B (p<0.05). After 5 weeks, FCM showed that the percentage of CD3+ T cells in peripheral blood was higher in Group B than Group C (p<0.05). MLR and skin graft studies showed that the thymus grafts had re-established a peripheral blood T lymphocyte function in Groups B and C and induced low donor-specific immune responses. Skin allografts had survived 2-3 days longer in Group B than in Group C. Additionally, the lymphocyte reaction to the donor was lower in Group B than Group C (15.1% vs 20.5%), but the lymphocyte reaction to third-party cell stimulation was stronger in Group B than Group C (94.4% vs 22.1%). Thus, larger graft volume (whole thymus) is more conducive to immune system reconstitution in the recipient and protecting the donated graft from rejection. PMID- 20362673 TI - Quantitative detection of DNA methylation states in minute amounts of DNA from body fluids. AB - Quantitative and reliable estimation of DNA methylation levels for multiple genomic regions pose a major challenge where starting DNA is available in very low quantity. Here we review major advances in the development of techniques for quantitative detection of DNA methylation in minute amount of DNA and describe a detailed protocol for quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification (qMAMBA), a combination of techniques that allows quantitative and sensitive detection of DNA methylation at multiple CpG sites and for multiple gene assays. Recently we successfully used this technique to quantitatively detect DNA methylation for a set of cancer-related genes in lung cancer patient plasma samples [18]. This method involves genome-wide amplification of bisulfite-modified DNA template followed by quantitative methylation detection using pyrosequencing. This allows a precise assessment of DNA methylation at CpG sites and could be adapted for high-throughput settings. It can also be applied in conjunction with studies involving single-cells or laser capture microdissected samples. Thus, this method should facilitate DNA methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies. PMID- 20362674 TI - DNA methylation detection using MS-qFRET, a quantum dot-based nanoassay. AB - Detection of aberrant promoter hypermethylation of tumor suppressor genes can be used as a prognostic or predictive marker for carcinogenesis. Since epigenetic modifying agents are FDA approved for treatment of patients with myelodysplastic syndrome, laboratory correlative tools to monitor response to this targeted therapy are important. Methylation specific quantum dot fluorescence resonance energy transfer (MS-qFRET) is a nanotechnology assay that enables the detection of methylation and its changes in a sensitive, quantifiable manner. It utilizes quantum dot-mediated fluorescence resonance energy transfer to achieve highly sensitive detection of DNA methylation. Template DNA is first treated with sodium bisulfite such that unmethylated cytosines are converted to uracil while methylated cytosines remain unconverted. Thereafter, the converted template is amplified using biotinylated methylation-specific primers. Quantum dots, functionalized with streptavidin, serve both as a scaffold to capture amplicons and as a donor for transferring energy to the Cy5 acceptor that is incorporated into the amplicons during PCR. Thus, the status of DNA methylation can be determined according to the level of FRET. In this report, MS-qFRET is validated in cell lines and then used to detect the status of p15(INK4B) methylation in clinical samples from eight patients with acute myeloid leukemia. PMID- 20362675 TI - Disease modeling in multiple sclerosis: assessment and quantification of sources of variability in brain parenchymal fraction measurements. AB - The measurement of brain atrophy from magnetic resonance imaging (MRI) has become an established method of estimating disease severity and progression in multiple sclerosis (MS). Most commonly reported in the form of brain parenchymal fraction (BPF), it is more sensitive to the degenerative component of the disease and shows progression more reliably than lesion burden. Typically, the reliability of BPF and other morphometric measurements is assessed by evaluating scan-rescan experiments. While these experiments provide good estimates of real-life error related to imperfect patient repositioning in the MRI scanner, measurement variance due to physiological and reversible pathological fluctuations in brain volume are not taken into account. In this work, we propose a new model for estimating variability in serial morphometry, particularly the BPF measurement. Specifically, we attempt to detect and explicitly model the remaining sources of error to more accurately describe the overall variability in BPF measurements. Our results show that sources of variability beyond subject repositioning error are important and cannot be ignored. We demonstrate that scan-rescan experiments only provide a lower bound on the true error in repeated measurements of patients' BPF. We have estimated the variance due to patient repositioning during scan-rescan (sigma(sr)(2) = 3.0e-06), variance assigned to physiological fluctuations (sigma(p)(2) = 5.74e-06) and the variance associated with lesion activity (sigma(les)(2) = 1.09e-05). These variance components can be used to determine the relative impact of their sources on sample size estimates for studies investigating change over time in MS patients. Our results demonstrate that sample size calculations based exclusively on scan-rescan variability (sigma(sr)) are likely to underestimate the number of patients required. If the physiological variability (sigma(p)) is incorporated in sample size calculations, the required sample size would increase by a factor of 5.69 based on standard t test sample size calculation. PMID- 20362676 TI - Distributed task coding throughout the multiple demand network of the human frontal-insular cortex. AB - The large variety of tasks that humans can perform is governed by a small number of key frontal-insular regions that are commonly active during task performance. Little is known about how this network distinguishes different tasks. We report on fMRI data in twelve participants while they performed four cognitive tasks. Of 20 commonly active frontal-insular regions in each hemisphere, five showed a BOLD response increase with increased task demands, regardless of the task. Although active in all tasks, each task invoked a unique response pattern across the voxels in each area that proved reliable in split-half multi-voxel correlation analysis. Consequently, voxels differed in their preference for one or more of the tasks. Voxel-based functional connectivity analyses revealed that same preference voxels distributed across all areas of the network constituted functional sub-networks that characterized the task being executed. PMID- 20362677 TI - Determining the optimal level of smoothing in cortical thickness analysis: a hierarchical approach based on sequential statistical thresholding. AB - The extent of smoothing applied to cortical thickness maps critically influences sensitivity, anatomical precision and resolution of statistical change detection. Theoretically, it could be optimized by increasing the trade-off between vertex wise sensitivity and specificity across several levels of smoothing. But to date neither parametric nor nonparametric methods are able to control the error at the vertex level if the null hypothesis is rejected after smoothing of cortical thickness maps. To overcome these drawbacks, we applied sequential statistical thresholding based on a simple hierarchical model. This methodology aims at controlling erroneous detections; firstly at the level of clusters, over smoothed statistical maps; and secondly at the vertex level, over unsmoothed statistical maps, by applying an adaptive false discovery rate (FDR) procedure to clusters previously detected. The superior performance of the proposed methodology over other conventional procedures was demonstrated in simulation studies. As expected, only the hierarchical method yielded a predictable false discovery proportion near the predefined FDR q-value for any smoothing level at the same time as being as sensitive as the others at the optimal setting. It was therefore the only method able to approximate the optimal size of spatial smoothing when the true change was assumed unknown. The hierarchical method was further validated in a cross-sectional study comparing moderate Alzheimer's disease (AD) patients with healthy elderly subjects. Results suggest that the extent of cortical thinning reported in previous AD studies might be artificially inflated by the choice of inadequate smoothing. In these cases, interpretation should be based on the location of local maxima of suprathreshold regions rather than on the spatial extent of the detected signal in the statistical parametric map. PMID- 20362678 TI - Cortical dynamics of visual change detection based on sensory memory. AB - Detecting a visual change was suggested to relate closely to the visual sensory memory formed by visual stimuli before the occurrence of the change, because change detection involves identifying a difference between ongoing and preceding sensory conditions. Previous neuroimaging studies showed that an abrupt visual change activates the middle occipital gyrus (MOG). However, it still remains to be elucidated whether the MOG is related to visual change detection based on sensory memory. Here we tried to settle this issue using a new method of stimulation with blue and red LEDs to emphasize a memory-based change detection process. There were two stimuli, a standard trial stimulus and a deviant trial stimulus. The former was a red light lasting 500 ms, and the latter was a red light lasting 250 ms immediately followed by a blue light lasting 250 ms. Effects of the trial-trial interval, 250 approximately 2000 ms, were investigated to know how cortical responses to the abrupt change (from red to blue) were affected by preceding conditions. The brain response to the deviant trial stimulus was recorded by magnetoencephalography. Results of a multi-dipole analysis showed that the activity in the MOG, peaking at around 150 ms after the change onset, decreased in amplitude as the interval increased, but the earlier activity in BA 17/18 was not affected by the interval. These results suggested that the MOG is an important cortical area relating to the sensory memory-based visual change detecting system. PMID- 20362679 TI - Structural asymmetries of perisylvian regions in the preterm newborn. AB - During the last trimester of human pregnancy, the cerebral cortex of foetuses becomes greatly and quickly gyrified, and post-mortem studies have demonstrated that hemispheres are already asymmetric at the level of Heschl gyrus, planum temporale and superior temporal sulcus (STS). Recently, magnetic resonance imaging (MRI) and dedicated post-processing tools enabled the quantitative study of brain development non-invasively in the preterm newborn. However, previous investigations were conducted either over the whole brain or in specific sulci. These approaches may consequently fail to highlight most cerebral sites, where anatomical landmarks are hard to delineate among individuals. In this cross sectional study, we aimed to blindly and automatically map early asymmetries over the immature cortex. Voxel-based analyses of cortical and white matter masks were performed over a group of 25 newborns from 26 to 36 weeks of gestational age. Inter-individual variations associated with increasing age were first detected in large cerebral regions, with a prevalence of the right hemisphere in comparison with the left. Asymmetries were further highlighted in three specific cortical regions. Confirming previous studies, we observed deeper STS on the right side and larger posterior region of the sylvian fissure on the left side, close to planum temporale. For the first time, we also detected larger anterior region of the sylvian fissure on the left side, close to Broca's region. This study demonstrated that perisylvian regions are the only regions to be asymmetric from early on, suggesting their anatomical specificity for the emergence of functional lateralization in language processing prior to language exposure. PMID- 20362680 TI - Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy. AB - The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models. PMID- 20362682 TI - Continuous motor sequence learning: cortical efficiency gains accompanied by striatal functional reorganization. AB - The acquisition and generation of action sequences constitute essential elements of purposeful human behavior. However, there is still considerable debate on how experience-driven changes related to skill learning are expressed at the neural systems level. The current functional magnetic resonance imaging (fMRI) study focused on changes in the neural representation of continuous movement sequences as learning evolved. Behavioral and neural manifestations of nonvisual motor practice were studied both within the time frame of a single scanning session, as well as after several days of extended practice. Based on detailed behavioral recordings which enabled the continuous characterization of the ongoing learning process at the single subject level, sequence-specific decreases in activation throughout a learning-related network of cortical areas were identified. Furthermore, the spatial layout of this cortical network remained largely unchanged after extensive practice, although further decreases in activation levels could be observed as learning progressed. In contrast, the posterior part of the left putamen showed increased activation levels when an extensively trained sequence needed to be recalled. Overall, these findings imply that continuous motor sequence learning is mainly associated with more efficient processing in a network of consistently recruited cortical areas, together with co-occurring activation pattern changes at the subcortical level. PMID- 20362681 TI - Grey matter and cognitive deficits in young relatives of schizophrenia patients. AB - Grey-matter volumetric and cognitive deficits in young, high-risk relatives of schizophrenia patients may be vulnerability markers of the illness. Although these markers may be correlated, it is unclear if their distributions in relatives overlap. We examined convergence of these markers in 94 young first and second-degree relatives (HR) and 81 healthy controls. Subjects were assessed using WCST, CPT-IP and Benton-Hamscher tests and on grey-matter volumes of brain regions related to language, attention and executive function using FreeSurfer to process T1-MR-images. K-means clustering using cognitive performance scores split relatives into sub-samples with better (HR+C, n=35) and worse (HR-C, n=59) cognition after controlling for age and gender. All regional volumes and language related regional laterality-indices were compared between HR-C, HR+C and control subjects, controlling for age, gender and intra-cranial volume. Volumes of caudate nuclei, thalami, hippocampi, inferior frontal gyri, Heschl's gyri, superior parietal cortices, supramarginal gyri, right angular gyrus, right middle frontal gyrus and right superior frontal gyrus, leftward laterality of supramarginal and inferior frontal gyri and rightward laterality of the angular gyrus were reduced in HR-C compared to controls. Volumes of Heschl's gyri, left supramarginal gyrus, inferior frontal gyri, hippocampi and caudate nuclei HR-C were smaller in HR-C compared to HR+C. HR+C showed deficits compared to controls only for the superior parietal and right angular volumes. Premorbid neuroanatomical and laterality alterations in schizophrenia may selectively manifest in cognitively compromised relatives. Overlapping structural and cognitive deficits may define a hyper vulnerable sub-sample among individuals at familial predisposition to schizophrenia. PMID- 20362683 TI - Age-related regional variations of the corpus callosum identified by diffusion tensor tractography. AB - The corpus callosum is the largest white matter connection in the human brain, and an understanding of its evolution with age in healthy individuals is one crucial aspect for determining its role in cognition and disease. Diffusion tensor imaging (DTI) allows for investigation of age-related callosal changes since tractography can both virtually reconstruct the segments of the corpus callosum in vivo based on unique target cortical regions, and provide quantitative diffusion parameters reflecting tissue microstructure. DTI tractography was used to subdivide the corpus callosum into seven distinct sections based on unique target areas (i.e., orbital frontal, anterior frontal, superior frontal, superior parietal, posterior parietal, temporal, and occipital) in a very large number of healthy volunteers (n=315) across a wide age range (5 59 years). Both fractional anisotropy (FA) and mean diffusivity (MD) changes with respect to age were fit with Poisson curves, showing increasing FA and decreasing MD during childhood and adolescence and slightly slower decreases of FA and increases of MD at older ages. Age at peak FA values and minimum MD values varied from 21 to 44 years, and an overall "outer-to-inner" trend was observed in which the anterior and posterior regions peaked earlier than central areas. In addition to these maturational trends of diffusion parameters reflecting the microstructural changes in the healthy corpus callosum over a large age range spanning childhood to older adulthood, these results can provide a baseline for identifying the presence and timing of callosal abnormalities in various brain disorders. PMID- 20362684 TI - Effect of inter-species, gender, and breeding on the mechanical behavior of brain tissue. AB - Mechanical response of brain tissue deforming at high rates are needed to build high-fidelity computer models for traumatic brain injury (TBI) studies. Different types of mammalian brains have been used to obtain the constitutive behavior of tissue. It is necessary to examine how these different brains compare to each other in order to determine which animal might be the best surrogate for human brain tissue. In this experimental study, fresh brain tissue from three different mammals, two types of porcine breeds, and genders were loaded under uniaxial compression over a wide range of strain rates. The experiments at higher rates were conducted with a Kolsky bar modified for soft tissue characterization, whereas lower rate experiments were performed on a conventional hydraulic material test frame. Experimental results did not show any significant difference in high-rate compressive response of the brain tissue of different animals, different breeds, and different genders. However, there was significant rate dependence for all tissues tested, especially in the Kolsky bar range. Further investigation is necessary to identify the source of the rate effects. PMID- 20362685 TI - Protein O-mannosylation in animal development and physiology: from human disorders to Drosophila phenotypes. AB - Protein O-mannosylation has a profound effect on the development and physiology of mammalian organisms. Mutations in genes affecting O-mannosyl glycan biosynthesis result in congenital muscular dystrophies. The main pathological mechanism triggered by O-mannosylation defects is a compromised interaction of cells with the extracellular matrix due to abnormal glycosylation of alpha dystroglycan. Hypoglycosylation of alpha-dystroglycan impairs its ligand-binding activity and results in muscle degeneration and failure of neuronal migration. Recent experiments revealed the existence of compensatory mechanisms that could ameliorate defects of O-mannosylation. However, these mechanisms remain poorly understood. O-mannosylation and dystroglycan pathway genes show remarkable evolutionary conservation in a wide range of metazoans. Mutations and downregulation of these genes in zebrafish and Drosophila result in muscle defects and degeneration, also causing neurological phenotypes, which suggests that O-mannosylation has similar functions in mammals and lower animals. Thus, future studies in genetically tractable model organisms, such as zebrafish and Drosophila, should help to reveal molecular and genetic mechanisms of mammalian O mannosylation and its role in the regulation of dystroglycan function. PMID- 20362687 TI - Effects of perfluorohexane vapor in the treatment of experimental lung injury. AB - RATIONALE: We investigated the effects of vaporized perfluorohexane (PFH) on pulmonary vascular tone, pulmonary vascular resistance and peak inspiratory pressure as well as lipid mediator formation in the treatment of calcium ionophore induced lung injury in a model of the isolated perfused and ventilated rabbit lungs. METHODS: Lung injury was induced in isolated perfused and ventilated rabbit lungs by calcium ionophore A23187. Lungs were treated with either 4.5 vol.% (4.5 vol.% PFH; n = 6) or 18 vol.% (18 vol.% PFH; n = 6) PFH. Six lungs remained untreated (Control). In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Mean pulmonary artery pressure (mPAP), peak inspiratory pressure (P(max)), and lung weight (weight) were monitored for 120 min. Experiments were terminated before when the increase in lung weight exceeded 40 g. Perfusate samples were taken at regular intervals for analysis of TXB(2), 6-keto-PGF(1) and LTB(4). RESULTS: Controls reached the study end point significantly earlier than both PFH groups. Significant differences were found for a weight gain of 10 g and 20 g between the control and the 4.5 vol.% PFH and the 18 vol.% PFH. Differences in mPAP were more pronounced in the 4.5 vol.% PFH. However increases in P(max) were more marked in 4.5 vol.% PFH. TXA(2)-, PGI(2)-, and LTB(4)-levels were significantly lower in PFH groups. Uninjured lungs remained unaffected by the presence of 18 vol.% PFH. CONCLUSION: Inflammatory lung injury was attenuated by the treatment with 4.5 vol.% PFH and 18 vol.% PFH vapor in the isolated perfused rabbit lung. Therapeutic effects were more pronounced with a concentration of 4.5 vol.% PFH. PMID- 20362686 TI - Characterization of Aspergillus nidulans DidB Did2, a non-essential component of the multivesicular body pathway. AB - ESCRT-III heteropolymers mediate membrane protein cargo sorting into multivesicular endosomes for subsequent vacuolar degradation. We studied the localization of largely uncharacterized Aspergillus nidulans ESCRT-III using its key structural component Vps32 and the 'associated' component DidB(Did2). Vps32 GFP localizes to motile early endosomes as reported, but predominates in aggregates often associated with vacuoles due to inability to dissociate from endosomes. DidB(Did)(2) regulating Vps4 (the ATPase disassembling ESCRT-III) is not essential. Consistent with this accessory role, didB Delta is unable to block the MVB sorting of the glutamate transporter AgtA, but increases its steady-state level and mislocalizes a fraction of the permease to the plasma membrane under conditions promoting its vacuolar targeting. didB Delta exacerbates the dominant negative growth defect resulting from Vps32-GFP over-expression. A proportion of DidB-GFP is detectable in early endosomes colocalizing with RabA(Rab5) and accumulating in nudA1 tips, suggesting that ESCRT-III assembles on endosomes from the early steps of the endocytic pathway. PMID- 20362688 TI - RNAi-mediated suppression of constitutive pulmonary gene expression by small interfering RNA in mice. AB - The ability of synthetic small interfering RNA (siRNA) to silence gene expression makes it a useful tool in biomedical research. However, effective and non-toxic functional siRNA delivery to mouse lungs in vivo is still a key challenge, and regulation of constitutively expressed genes is poorly characterized. Following in vitro validation of siRNA molecules, naked, stabilized siRNA (AtuRNAi) was applied intranasally (i.n.) by droplets or intratracheally (i.t.) by MicroSprayer in female C57BL/6 mice. Distribution of Cy3-tagged siRNAs was examined. Pulmonary expression of ubiquitously (lamin B1) or cell-specific (E-cadherin, VE-cadherin), constitutive genes was analysed by TaqMan-realtime-PCR. Further, formulated lipoplex-siRNA, which has enhanced transfection efficiency, was applied i.t. or intravenously (i.v.). Single i.t. as compared to i.n. application of unformulated siRNA resulted in higher delivery efficiency and homogenous pulmonary distribution. After inhalation of target-specific siRNA, reduction of epithelial E-cadherin by 21%, but no significant reduction of endothelial VE-cadherin or ubiquitously expressed lamin B1 was observed. Pharmacokinetic analysis revealed rapid transfer of intact siRNA molecules into the vascular system and accumulation in the kidneys, calling lung specificity into question. I.t. application of lipoplex-siRNA evoked inflammation. In contrast, i.v. application of lipoplex-siRNA specifically reduced expression of VE-cadherin mRNA by about 50% in lungs without evoking lung cellular influx. In conclusion, sufficient pulmonary distribution of aerosolized siRNA was attained in mice by MicroSprayer, however development of appropriate siRNA carriers is highly desirable to improve lung-specific functional inhalative siRNA delivery. Pulmonary knockdown of constitutive endothelial targets by 50% was achieved by i.v. application of lipoplex-siRNA. PMID- 20362689 TI - Tiotropium bromide exerts anti-inflammatory activity in a cigarette smoke mouse model of COPD. AB - Tiotropium bromide is a long acting muscarinic antagonist (LAMA), marketed under the brand name Spiriva, for the treatment of chronic obstructive pulmonary disease (COPD). Besides its proven direct bronchodilatory activity, recent clinical studies demonstrated that tiotropium is able to reduce the exacerbation rate and impact the clinical course of COPD. One significant pathological feature believed to be causative for the progressive nature of COPD is chronic pulmonary inflammation. The aim of the present study was to investigate the anti inflammatory activity of tiotropium on cigarette smoke-induced pulmonary inflammation in mice. C57Bl/6 mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6h per day to elicit pulmonary inflammation and mediator release. One hour before smoke exposure, animals were treated with tiotropium by inhalation (0.01-0.3mg/mL) for 5 min; 18h after the last CS exposure a bronchoalveolar lavage was performed. Tiotropium concentration dependently inhibited pulmonary neutrophilic inflammation with an IC(50) of 0.058 mg/mL and a maximum inhibition of 60% at 0.3mg/mL. Furthermore, the CS-induced pulmonary release of leukotriene B(4), interleukin-6, keratinocyte-derived chemokine, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha and -2, and tumor necrosis factor alpha was dose-dependently reduced. The bronchodilatory activity of tiotropium against acetycholine-induced bronchoconstriction was found to be in the same dose range as the anti inflammatory activity with an IC(50) of 0.045 mg/mL and a maximum bronchodilation of 90% at 0.3mg/mL. Our data suggest that the beneficial effects of tiotropium on the course of COPD shown in patients may be associated with an anti-inflammatory activity. PMID- 20362690 TI - Autonomic regulation of the heart during digestion and aerobic swimming in the European sea bass (Dicentrarchus labrax). AB - The autonomic regulation of the heart was studied in European sea bass (Dicentrarchus labrax) during digestion and aerobic exercise by measuring cardiac output (Q), heart rate (f(H)), stroke volume (V(s)) and oxygen consumption (MO(2)) before and after pharmacological blockade by intraperitoneal injections of atropine and propranolol. The significant rise in MO(2) (134+/-14 to 174+/-14 mg kg(-)(1)h(-)(1)) 6h after feeding (3% body mass) caused a significant tachycardia (47.7+/-10.9 to 72.6+/-7.2 beats min(-)(1)), but only a small elevation of Q. MO(2) of fasting fish increased progressively with swimming speed (0.7-2.1BLs(-)(1)) causing a significant tachycardia (43+/-6 to 61+/-4 mL min( )(1)kg(-)(1)) and increased Q but V(s) did not change. Inactive fish were characterized by a high vagal tone (98.3+/-21.7%), and the tachycardia during digestion and exercise was exclusively due to a reduction of vagal tone, while the adrenergic tone remained low during all conditions. Intrinsic f(H), revealed after double autonomic blockade, was not affected by digestion (71+/-4 and 70+/-6 min(-)(1), respectively), indicating that non-adrenergic, non-cholinergic (NANC) factors do not contribute to the tachycardia during digestion in sea bass. PMID- 20362691 TI - Relationship among circulating hemoglobin, nitric oxide synthase activities and angiogenic poise in red- and white-blooded Antarctic notothenioid fishes. AB - Nitric oxide (NO)-mediated angiogenesis may play a role in establishing dense retinal vasculatures of Antarctic hemoglobinless icefishes (suborder: Notothenioidei). We hypothesized that loss of hemoglobin (Hb) leads to elevation in [NO] due to decreased degradation of the compound when the NO-scavenger Hb is absent, thereby inducing vascular growth. We found that total mass of NO metabolites, nitrite plus nitrate (NO(x)), in plasma is greater in icefishes than in red-blooded notothenioids [e.g. C. aceratus (Hb-), 22.7+/-2.9 microM; N. coriiceps (Hb+), 14.7+/-1.7 microM], suggesting a higher NO load in hemoglobinless animals. High NO levels do not appear to be a result of greater NO synthesis; we consistently measured lower activities of the enzyme catalyzing NO production, nitric oxide synthase, in tissues of icefishes than in Hb-expressing notothenioids [e.g. 96+/-10 and 216+/-39 pmol(min g wet wt)(-1) in brain tissue of C. aceratus (Hb-) and G. gibberifrons (Hb+), respectively]. Levels of mRNA for hypoxia-induced (HIF-1alpha and PHD2) and angiogenic genes (VEGF) were similar in red- and white-blooded species, indicating that vascular maintenance in adult animals does not require differences in angiogenic tone. This does not preclude a cause-and-effect relationship between absence of Hb and NO-mediated angiogenesis during earlier ontogenetic stages of icefishes. PMID- 20362692 TI - Mycosporine-like amino acid content in the sea anemones Aulactinia marplatensis, Oulactis muscosa and Anthothoe chilensis. AB - The occurrence of mycosporine-like amino acids (MAAs) in the sea anemones Aulactinia marplatensis (Zamponi, 1977), Oulactis muscosa (Drayton in Dana, 1846) and Anthothoe chilensis (Lesson, 1830), from the rocky intertidal habitats on the coast of Mar del Plata, Argentina, was assessed by HPLC. The pattern of MAAs in the mussel Brachidontes rodriguezi, main component of the diet for A. marplatensis and O. muscosa, was as well determined. The results were comparatively analyzed together and with previously reported MAA content in species mainly of the genus Anthopleura. The correlation between the MAA concentration and light availability of their habitats is in line with the photoprotective role assigned to the compounds. The high proportion of mycosporine-taurine in the three species and the results for the evaluation of MAAs in the mussels point to a non-dietary origin or a regulated biotransformation metabolism of dietary MAAs and/or their precursors that is common to sea anemones. PMID- 20362693 TI - Pharmacophore modeling and applications in drug discovery: challenges and recent advances. AB - Pharmacophore approaches have become one of the major tools in drug discovery after the past century's development. Various ligand-based and structure-based methods have been developed for improved pharmacophore modeling and have been successfully and extensively applied in virtual screening, de novo design and lead optimization. Despite these successes, pharmacophore approaches have not reached their expected full capacity, particularly in facing the demand for reducing the current expensive overall cost associated with drug discovery and development. Here, the challenges of pharmacophore modeling and applications in drug discovery are discussed and recent advances and latest developments are described, which provide useful clues to the further development and application of pharmacophore approaches. PMID- 20362694 TI - The impact of fish spawning on metal and protein levels in gastrointestinal cytosol of indigenous European chub. AB - The study presented here reports for the first time cytosolic metal and protein levels in the gastrointestinal tissue of field-collected European chub (Squalius cephalus), living in low metal-contaminated river section. In two sub-cellular fractions (untreated cytosol and heat-treated cytosol), isolated from the whole gastrointestinal tract of indigenous chubs collected during spawning (April/May 2006) and post-spawning period (September 2006), seasonal or gender related differences of trace metals and proteins were determined. In both fractions, cytosol and heat-treated cytosol, metal levels decrease as follows: Zn>Fe>Cu>Mn>Cd and are significantly higher during the spawning period. Besides that, the level of heat-sensitive proteins (metalloenzymes) in cytosolic fractions is also significantly higher during the spawning period in both male and female specimens. Higher condition indices of chubs in the spawning period imply higher feeding activity, energy reserves and recent growth of indigenous chubs. Metallothionein levels, determined in the heat-treated cytosol, are comparable in gastrointestinal tract of feral chubs collected in both seasons and confine the background metallothionein levels, on average 3mgg(-)(1) wet tissue. Chub spawning has been identified as a confounding factor, having an impact on cytosolic metal and protein levels, presumably due to enhanced food supply (higher condition indices) and fish spawning (higher gonadosomatic indices in some male specimens). PMID- 20362696 TI - How far are induced pluripotent stem cells from the clinic? AB - Induced pluripotent stem cells (iPSCs) can be derived from diverse different somatic cells and share many of the characteristics of embryonic stem cells (ESCs). Because iPSCs avoid many of the ethical concerns associated with the use of embryonic or fetal material, iPSCs have great potential in cell-based regenerative medicine. However, several hurdles will need to be surmounted before their potential can be realized in therapeutic applications. For example, the use of viral vectors, some of which are oncogenes raises the risk of tumor formation in patients, the differentiation of iPSCs into required functional cells in vivo remains to be established, the obtaining of pure populations of target cells from iPSCs is still difficult. Of these, some are shared by both iPSCs and ESCs, others are unique to iPSCs. We will describe these stumbling blocks in detail and discuss possible ways to overcome them. Despite many significant advances, there is as yet no technological framework that would allow the exploitation of iPSCs in a clinical setting in the immediate future. Further research will be required before directed reprogramming can provide a source of cells suitable for application in regenerative medicine. PMID- 20362695 TI - Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. AB - BACKGROUND & AIMS: Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. METHODS: Standard case report forms from 2740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, together with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital. RESULTS: There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases; 0.6%). There were no biopsy-related deaths. The bleeding rate was higher among patients with platelet counts of 60,000/mm(3) or less and among those with an international normalized ratio of 1.3 or greater, although none of the patients with an international normalized ratio greater than 1.5 bled. Excluding subjects with a platelet count of 60,000/mm(3) or less would have reduced the bleeding rate by 25% (4 of 16), eliminating only 2.8% (77 of 2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events. CONCLUSIONS: Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts of 60,000/mm(3) or less. PMID- 20362697 TI - No or only population-specific effect of PON1 on human longevity: a comprehensive meta-analysis. AB - Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet). PMID- 20362698 TI - Aquaporin 5 expression inhibited by LPS via p38/JNK signaling pathways in SPC-A1 cells. AB - Proper H(2)O to mucin ratio of airway mucus is important for mucociliary clearance. Recent studies suggest that decreased aquaporin 5 (AQP5) is correlated with increased staining of MUC5AC in submucosal glands of COPD patients. Lipopolysaccharide (LPS) is one of the major insults in airway mucin secretion in COPD. In this study, changes in both AQP5 and MUC5AC expression levels in SPC-A1, a human airway submucosal gland cell line, were quantified after exposure of the cells to LPS. AQP5 transcription and protein expression were decreased while MUC5AC expression was increased by LPS exposure in SPC-A1 cells. Further studies revealed that AQP5 expression was down-regulated via the p38/JNK signaling pathway, while MUC5AC was up-regulated through the EGFR-p38/JNK pathway. Therefore, p38 and JNK may become promising targets to preserve AQP5 expression and prevent MUC5AC over-expression to restore proper H(2)O to mucin ratio of the airway mucus, which may be beneficial to the clinical management of COPD patients. PMID- 20362699 TI - Effect of different glucose concentrations on proteome of Saccharomyces cerevisiae. AB - We performed a proteomic study to understand how Saccharomyces cerevisiae adapts its metabolism during the exponential growth on three different concentrations of glucose; this information will be necessary to understand yeast carbon metabolism in different environments. We induced a natural diauxic shift by growing yeast cells in glucose restriction thus having a fast and complete glucose exhaustion. We noticed differential expressions of groups of proteins. Cells in high glucose have a decreased growth rate during the initial phase of fermentation; in glucose restriction and in high glucose we found an over-expression of a protein (Peroxiredoxin) involved in protection against oxidative stress insult. The information obtained in our study validates the application of a proteomic approach for the identification of the molecular bases of environmental variations such as fermentation in high glucose and during a naturally induced diauxic shift. PMID- 20362700 TI - Familial occurrence of ptosis, nasal speech, prominent ears, hand anomalies and learning problems. AB - We describe a four-generation family in whom 5 members show the combination of a large head, ptosis, nasal speech that sometimes goes along with a cleft palate, full cheeks, small mouth, and prominent ears, and who also have learning problems. We evaluated three affected members in detail and found them to have in addition a partial cutaneous syndactyly between the third and fourth fingers, an increased distance between second and third finger, and a decreased smell. We have not been unable to find other patients described in literature with the same combination of features, and suggest this to represent a hitherto unrecognizable entity. Pattern of inheritance is likely to be autosomal dominant. PMID- 20362701 TI - Effect of HIP/ribosomal protein L29 deficiency on mineral properties of murine bones and teeth. AB - Mice lacking HIP/RPL29, a component of the ribosomal machinery, display increased bone fragility. To understand the effect of sub-efficient protein synthetic rates on mineralized tissue quality, we performed dynamic and static histomorphometry and examined the mineral properties of both bones and teeth in HIP/RPL29 knock out mice using Fourier transform infrared imaging (FTIRI). While loss of HIP/RPL29 consistently reduced total bone size, decreased mineral apposition rates were not significant, indicating that short stature is not primarily due to impaired osteoblast function. Interestingly, our microspectroscopic studies showed that a significant decrease in collagen crosslinking during maturation of HIP/RPL29-null bone precedes an overall enhancement in the relative extent of mineralization of both trabecular and cortical adult bones. This report provides strong genetic evidence that ribosomal insufficiency induces subtle organic matrix deficiencies which elevates calcification. Consistent with the HIP/RPL29 null bone phenotype, HIP/RPL29-deficient teeth also showed reduced geometric properties accompanied with relative increased mineral densities of both dentin and enamel. Increased mineralization associated with enhanced tissue fragility related to imperfection in organic phase microstructure evokes defects seen in matrix protein-related bone and tooth diseases. Thus, HIP/RPL29 mice constitute a new genetic model for studying the contribution of global protein synthesis in the establishment of organic and inorganic phases in mineral tissues. PMID- 20362702 TI - The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats. AB - Critical size segmental bone defects are still a major challenge in reconstructive orthopedic surgery. Transplantation of human mesenchymal stem cells (hMSC) has been proposed as an alternative to autogenous bone graft, as MSC can be expanded in vitro and induced to differentiate into bone-regenerating osteoblasts by several bone morphogenetic proteins (BMP). The aim of this study was to investigate whether the association of hMSC and BMP-7, with providing the necessary scaffold to fill the bone loss, improved bone regeneration in a rat model of critical size segmental bone defect, compared to treatment with either hMSC or BMP-7 and the matrix. In addition, we tested whether pre-treatment of hMSC with cyclic ADP-ribose (cADPR), an intracellular Ca2+ mobilizer previously shown to accelerate the in vitro expansion of hMSC (Scarfi S et al, Stem Cells, 2008), affected the osteoinductive capacity of the cells in vivo. X-ray analysis, performed 2, 10 and 16 weeks after transplantation, revealed a significantly higher score in the rats treated with hMSC and BMP-7 compared to controls, receiving either hMSC or BMP-7. Microtomography and histological analysis, performed 16weeks after transplantation, confirmed the improved bone regeneration in the animals treated with the association of hMSC and BMP-7 compared to controls. Pre-treatment with cADPR to stimulate hMSC proliferation in vitro did not affect the bone regenerating capacity of the cells in vivo. These results indicate that the association of in vitro expanded hMSC with BMP-7 provide a better osteoinductive graft compared to either hMSC or BMP-7 alone. Moreover, cADPR may be used to stimulate hMSC proliferation in vitro in order to reduce the time required to obtain a transplantable number of cells, with no adverse effect on the bone regenerating capacity of hMSC. PMID- 20362703 TI - FGFR3 signaling induces a reversible senescence phenotype in chondrocytes similar to oncogene-induced premature senescence. AB - Oncogenic activation of the RAS-ERK MAP kinase signaling pathway can lead to uncontrolled proliferation but can also result in apoptosis or premature cellular senescence, both regarded as natural protective barriers to cell immortalization and transformation. In FGFR3-related skeletal dyplasias, oncogenic mutations in the FGFR3 receptor tyrosine kinase cause profound inhibition of cartilage growth resulting in severe dwarfism, although many of the precise mechanisms of FGFR3 action remain unclear. Mutated FGFR3 induces constitutive activation of the ERK pathway in chondrocytes and, remarkably, can also cause both increased proliferation and apoptosis in growing cartilage, depending on the gestational age. Here, we demonstrate that FGFR3 signaling is also capable of inducing premature senescence in chondrocytes, manifested as reversible, ERK-dependent growth arrest accompanied by alteration of cellular shape, loss of the extracellular matrix, upregulation of senescence markers (alpha-GLUCOSIDASE, FIBRONECTIN, CAVEOLIN 1, LAMIN A, SM22alpha and TIMP 1), and induction of senescence-associated beta-GALACTOSIDASE activity. Our data support a model whereby FGFR3 signaling inhibits cartilage growth via exploiting cellular responses originally designed to eliminate cells harboring activated oncogenes. PMID- 20362704 TI - Vertebral fractures in the elderly may not always be "osteoporotic". AB - INTRODUCTION: Vertebral fractures in the elderly are often assumed to be "osteoporotic" and require anti-osteoporosis therapy. However, some of these fractures may represent traumatic injuries to vertebrae that have comparatively normal bone mineral density (BMD). We hypothesize that radiographic appearances can be used to differentiate between "osteoporotic" fractures of vertebrae with low BMD and strength, and "traumatic" fractures of vertebrae with normal BMD and strength. METHODS: 73 cadaveric specimens (each comprising two vertebrae with the intervening intervertebral disc and ligaments) were obtained from donors aged 42 to 91 (mean 74) years. Areal BMD was measured in the lateral projection for each vertebral body, using DXA. Each specimen was secured in metal cups containing dental plaster, and compressed to failure at 3mm/s on a computer-controlled materials testing machine. Mechanical failure was detected by a reduction in the gradient of the load-deformation curve. Compressive deformation for each specimen was limited to 4mm in order to prevent gross destruction of the vertebra. Radiographs, obtained before and after mechanical loading, were assessed by an experienced radiologist (GJ) who was blinded to BMD and mechanical data. The algorithm-based qualitative method (ABQ) was used to assign each specimen to two possible outcomes: no discernible fracture of either vertebra, or fracture. The latter were further classified into specimens with osteoporotic fracture and those with traumatic fracture, by applying additional criteria for differential diagnosis. The relationship of failure load to BMD was tested using correlation. BMD and failure load for the three diagnostic outcomes were compared using one way analysis of variance (ANOVA). RESULTS: Failure load was proportional to BMD (R=0.63, p<0.001). "Osteoporotic," "traumatic" and "no discernible" fractures were reported in 16, 26 and 31 specimens respectively. "Traumatic" fracture specimens had higher BMD and failed at higher loads than "osteoporotic" fracture specimens (p<0.05). CONCLUSIONS: Some vertebral fractures in the elderly may be traumatic rather than osteoporotic in origin. Our radiological criteria help to differentiate between them. PMID- 20362705 TI - Reply to Meyer. PMID- 20362706 TI - Need for a unified decision-making tool for ultrafiltration therapy in heart failure; call for action. AB - Although ultrafiltration portends several theoretical advantages over the standard therapy for acute decompensated heart failure, it might not be the optimal treatment for all patients presenting with an episode of decompensation. It is not yet clear how to prospectively identify the subset of patients that would benefit from this therapeutic modality. Based on the pathophysiologic mechanisms underlying acute decompensated heart failure, early ultrafiltration therapy can be an appropriate initial management strategy for those patients with diuretic resistance whose associated renal dysfunction is related to hemodynamic changes rather than a structural abnormality. In the absence of widely accepted consensus guidelines, ultrafiltration use is currently subject to considerable variations among physicians. A clinical tool (eg, a scoring system) that is based on the individual patient's characteristics is therefore needed to prospectively identify the appropriate candidates for this therapy. Using this system is likely to portend better outcomes while helping to avoid unnecessary exposure to potential risks of extracorporeal therapies. PMID- 20362707 TI - Bridging the gap between clinical trials of antiplatelet therapies and applications among elderly patients. AB - Although patients aged > or =75 years represent nearly 40% of all those hospitalized with acute coronary syndromes, their enrollment in trials of therapeutic interventions has been relatively modest. Thus, scarce information exists to guide clinicians in decision-making and assessing projections of safety and efficacy for antiplatelet agents. The pathobiology of aging, including age related changes in vascular repair and integrity, applies to patient management and offers a platform for investigation. Because older patients receive excess dosing of antithrombotic agents much more often than their younger counterparts do, initial steps toward optimized care include attention to indications, dosing, and duration of treatment. This review, representing a summary of information presented at the Fourth Annual Platelet Colloquium held in Washington, DC, in January 2009 and supplemented with recent clinical trial results, underscores an increasingly narrow safety index for antiplatelet agents in the elderly and the all-important balance of safety and efficacy--a dynamic continuum that remains paramount in quality of care. Considerations for future trial designs, registries, and analyses of existing data are highlighted to better guide clinicians toward the optimal management of this rapidly growing, high-risk group. PMID- 20362708 TI - Meta-analysis of randomized trials on the efficacy of vascular closure devices after diagnostic angiography and angioplasty. AB - BACKGROUND: The aim of this meta-analysis was to evaluate the safety and efficacy of vascular closure devices (VCDs). METHODS: This meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews. RESULTS: The literature search yielded 31 prospective, randomized studies including 7,528 patients who were randomized to VCDs or manual/mechanical compression after diagnostic angiography and/or endovascular procedures. Most of these studies have excluded patients at high risk of puncture site complications. Meta-analysis showed similar results in the study groups in terms of groin hematoma, bleeding, pseudoaneurysm, and blood transfusion. Lower limb ischemia and other arterial ischemic complications (0.3% vs 0%, P = .07) as well as need of surgery for vascular complications (0.7% vs 0.4%, P = .10) were somewhat more frequent with arterial puncture closure devices. The incidence of groin infection was significantly more frequent with VCDs (0.6% vs 0.2%, P = .02). The use of VCD was uniformly associated with a significantly shorter time to hemostasis. Such differences where more evident in patients undergoing percutaneous coronary intervention, whereas these methods were associated with similar rates of adverse events among patients undergoing diagnostic coronary angiography. CONCLUSIONS: The use of VCDs is associated with a significantly shorter time to hemostasis and thus may shorten recovery. However, the use of VCDs is associated with a somewhat increased risk of infection, lower limb ischemia/arterial stenosis/device entrapment in the artery, and need of vascular surgery for arterial complications. Further studies are needed to get more conclusive results, particularly in patients at high risk of femoral puncture-related complications. PMID- 20362709 TI - Design and methods of the Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study. AB - BACKGROUND: Serial measurements of N-terminal pro-B type natriuretic peptide (NT proBNP) provide prognostic information in patients with chronic heart failure (HF). Changes in NT-proBNP concentrations parallel prognosis; however, it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT proBNP concentrations is superior to standard HF care alone. AIMS: The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to standard of care HF management. METHODS: In a prospective randomized single-center trial, subjects with New York Heart Association class II to IV systolic HF (left ventricular ejection fraction < or =40%) will be enrolled. Both groups will receive standard HF management (with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF), whereas one group ("NT-proBNP") will also have treatment adjustments to reduce NT-proBNP concentrations < or =1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period; secondary end points will include effects of NT-proBNP guided care on cardiac structure and function, quality of life, and total costs of care. RESULTS: Enrollment began in 2006; of the original 300 planned, thus far, 151 subjects have been randomized. Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm. Full results are expected in 2010. CONCLUSIONS: The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to standard of care HF management (www.clinicaltrials.gov identifier NCT00351390). PMID- 20362711 TI - Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention: design and rationale of the Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction (AIDA STEMI) trial. AB - BACKGROUND: Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction. The hypothesis of this trial is that abciximab bolus intracoronary in comparison to standard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI. STUDY DESIGN: The Abciximab Intracoronary versus intravenously Drug Application in STEMI (AIDA STEMI) study is a 1,912-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of AIDA STEMI is the composite of all cause mortality, recurrent MI, or new congestive heart failure within 90 days of randomization. The primary safety outcome assessment will be major bleeding. CONCLUSIONS: The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI, potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory. PMID- 20362710 TI - Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial. AB - BACKGROUND: Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. OBJECTIVES: The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. DESIGN: The multicenter Alpha Omega Trial is a randomized, double blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. RESULTS: The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrollment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. CURRENT STATUS: Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010. PMID- 20362712 TI - Rationale and design of the FreezeAF trial: a randomized controlled noninferiority trial comparing isolation of the pulmonary veins with the cryoballoon catheter versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation. AB - BACKGROUND: Atrial fibrillation is the most commonly encountered clinical arrhythmia, and there are an increasing number of patients with paroxysmal atrial fibrillation treated by catheter ablation. The criterion standard is the isolation of the pulmonary veins (PVs) using radiofrequency (RF) energy in combination with an open irrigated tip catheter. The procedure remains technically challenging with a significant number of complications. So far, no randomized comparisons between the outcome of cryoballoon versus RF ablation are available. STUDY DESIGN: The object of this randomized clinical trial is to compare the efficacy of isolating the PVs with either the cryoballoon or the open irrigated tip RF catheter. Two hundred forty-four patients with paroxysmal atrial fibrillation will be randomized for either RF or cryoballoon. With both techniques, PV isolation will be performed. Primary end point of the study is freedom from atrial fibrillation without antiarrhythmic drugs and without persistent complications at 6 and 12 months. Clinical success will be evaluated using Holter electrocardiogram and event recordings for at least 7 days. Within 6 months, no redo procedure is performed; and a redo after 6 months is performed with the previously used energy source. Secondary end points include the mid- and long-term clinical success, procedural data, and cost-effectiveness. CONCLUSION: The FreezeAF trial will examine for the first time in a randomized trial whether PV isolation with the cryoballoon is not relevantly inferior to open irrigated RF ablation in patients with paroxysmal atrial fibrillation during follow-up. It will additionally directly compare acute procedural success and safety of the procedures. PMID- 20362713 TI - Changes in beliefs about medications during long-term care for ischemic heart disease. AB - BACKGROUND: Beliefs such as self-reported low necessity for medications and high concerns about medications are associated with nonadherence. Changes in these beliefs during long-term care have not previously been studied and were evaluated for purposes of this analysis. METHODS: From January 2006 through September 2007, patients at 41 hospitals who met entry criteria for the CRUSADE Quality Improvement Initiative were consented for participation in a longitudinal follow up survey study called MAINTAIN. The patients completed The Beliefs about Medicines Questionnaire at 3 and 12 months postdischarge to assess necessity and concerns related to heart medications. Internal reliability and construct validity of the survey were evaluated at both time points. Changes in necessity and concern scores from 3 to 12 months were determined, and factors associated with negative changes were explored. RESULTS: A total of 812 patients completed both surveys. Internal reliability and construct validity were good. From 3 to 12 months, only 9.2% of patients shifted from a high to low necessity score; however, 20.7% of patients shifted from a low to high concern score. Factors found to be statistically significantly and independently associated with increased concern were the perception that the provider did not listen carefully to the patient (odds ratio [OR] 2.63, 95% CI 1.49-4.76), depression at 12 months (OR 2.95, 95% CI 1.57-5.55), hospital discharge with > or =7 medications (OR 1.71, 95% CI 1.07-2.74), and not receiving a medication list/instructions at hospital discharge (OR 1.69, 95% CI 1.05, 2.78). Factors associated with decreased necessity included not having a cardiologist (OR 2.26, 95% CI 1.34 3.83) and nonpersistence at 12 months with lipid-lowering medication (OR 1.85, 95% CI 1.01-3.45). CONCLUSIONS: One third of the patients reported a negative change in their beliefs about heart medications. Although some changes were observed in perceived necessity, negative changes in concerns occurred in 1 of every 5 patients. Interventions that address these concerns may be useful in improving adherence and clinical outcomes. PMID- 20362714 TI - Ischemia-modified albumin levels predict long-term outcome in patients with acute myocardial infarction. The French Nationwide OPERA study. AB - BACKGROUND: Little is known about the capacity of ischemia-modified albumin (IMA) plasma concentration to predict long-term cardiac outcome in patients with established acute myocardial infarction (AMI). Because IMA is a marker of ischemia rather than myocardial cell damage, we hypothesized that IMA plasma levels could provide additional prognostic value to classic clinical and biological risk markers in patients with AMI. Therefore, we investigated the predictive value of plasma IMA in patients with AMI enrolled in the French Nationwide OPERA study. METHODS: Plasma concentrations of IMA and other cardiac biomarkers (troponin, C-reactive protein, B-type natriuretic peptide) were measured within 24 hours of hospital admission in 471 patients hospitalized with an AMI (defined using European Society of Cardiology/American College of Cardiology criteria). Patients' characteristics, cardiovascular risk factors and treatments, and clinical outcomes were recorded. Univariate and multivariable predictors of cardiac outcome in-hospital and at 1 year were identified. RESULTS: The primary composite end point (death, resuscitated cardiac arrest, recurrent myocardial infarction or ischemia, heart failure, stroke) occurred in 75 (15.6%) patients in-hospital and in 144 (30.6%) at 1 year: 40% of patients in the highest IMA quartile (>104 IU/mL) reached the end point compared with 20% in the lowest (<83 IU/mL) by 1 year. Multivariable logistic regression analysis identified 4 independent predictors of composite end point at 1 year: plasma concentrations of IMA (P = .01), brain natriuretic peptide (P = .001), heart failure (P = .005), and age (P = .003). CONCLUSIONS: In patients with AMI, IMA measured within 24 hours is a strong and independent predictor of cardiac outcome at 1 year and may help identify those requiring more aggressive medical management. PMID- 20362715 TI - In-hospital mortality in 13,263 survivors of out-of-hospital cardiac arrest in Canada. AB - BACKGROUND: There is a substantial mortality rate in patients admitted alive after out-of-hospital cardiac arrest. The primary objective of our study was to examine trends in in-hospital survival in out-of-hospital cardiac arrest survivors in Canada between 1994 and 2004. The secondary objective was to examine predictors of in-hospital survival in these patients. METHODS: Data on hospital admissions from April 1, 1994, to March 31, 2004, were obtained from the Health Person-oriented Information Database, maintained by Statistics Canada. We included all patients with a primary diagnosis of cardiac arrest who survived to hospital admission. We assessed survival to hospital discharge in all patients admitted alive. RESULTS: In Canada, 13,263 patients survived community arrest between 1994 and 2004. The annual incidence of hospital admission after out-of hospital cardiac arrest decreased by 33%, from 5.37 per 100,000 in 1994 to 3.63 per 100,000 in 2004 (P < .0001 for trend). Subsequently, 5,045 patients (38.03%) survived to hospital discharge. The survival rate did not change during the duration of the study. Invasive coronary artery disease management was associated with a greatly increased chance of survival (odds ratio 21.98, 95% CI 17.62 27.42). Also male gender, heart failure, and acute myocardial ischemia were independent positive predictors of survival to hospital discharge; greater age and comorbidities were negative predictors of survival. Finally, there were significant interprovincial variations in survival rates. CONCLUSIONS: Our study, the largest of its kind, has 4 main findings. Firstly, between 1993 and 2004, there was a significant and steady decline in admission rates after community cardiac arrest. Second, there was no change in the in-hospital survival rates. Thirdly, invasive management of coronary artery disease was associated with a greatly improved chance of survival, and finally, there were important regional variations in survival rates. PMID- 20362716 TI - The relationship between coronary stenosis severity and compression type coronary artery movement in acute myocardial infarction. AB - BACKGROUND: Acute myocardial infarction is thought to occur at sites of minor coronary stenosis. Recent data challenge this and also propose a role for coronary artery movement (CAM) in plaque instability. We examined the relationship between coronary stenosis severity, CAM pattern, and infarct-related lesions (IRLs) in acute myocardial infarction. METHODS: We investigated 203 consecutive patients with ST-segment elevation myocardial infarction after successful fibrinolysis. Quantitative coronary angiography, CAM pattern, and extent score (atheroma burden) analysis was performed for each coronary artery segment. RESULTS: The IRL stenosis was at least moderate (>50%) and severe (>70%) in 78% and 31% of patients, respectively. Culprit arteries were associated with higher atheroma extent scores (25.2 vs 21.6, P < .001). Analysis of 2,228 coronary segments showed that stenosis severity and IRLs were highly correlated, such that the likelihood of being a culprit segment progressively increased with worsening stenosis (odds ratio [OR] 30.0, 95% confidence interval [CI] 19.0-47.6, P < .001, for >70% vs <30% stenosis). Compression CAM was also strongly associated with culprit segments (OR 3.4, 95% CI 2.6-4.5, P < .001). In addition, compression CAM and stenosis severity were strongly correlated, with the likelihood of a coronary segment having compression CAM progressively increasing with worsening stenosis (OR 56.4, 95% CI 37.9-83.8, P < .001, for >70% vs <30% stenosis). CONCLUSIONS: In patients with ST-segment elevation myocardial infarction, there is a strong relationship between stenosis severity and IRLs. Our study also raises the hypothesis that compression CAM may accelerate atherosclerosis and predispose to plaque vulnerability. PMID- 20362717 TI - QRS prolongation in patients with acute coronary syndromes. AB - BACKGROUND: QRS prolongation with or without bundle branch block (BBB) has been associated with adverse outcome in myocardial infarction; we examined the relationship between QRS duration and outcome in a broad spectrum of patients with acute coronary syndrome (ACS). METHOD AND RESULTS: Core laboratory evaluation of the presenting electrocardiogram in Canadian ACS Registry patients (n = 5,003) showed 4,289 (85.7%) had QRS <120 milliseconds, 202 (4.0%) patients had QRS > or =120 milliseconds without BBB, 262 (5.2%) had left BBB (LBBB), and 250 (5.0%) had right BBB. Compared to patients with QRS <120 milliseconds, patients with QRS > or =120 milliseconds without BBB had higher in-hospital (3.5% vs 1.9%, odds ratio [OR] 1.87, 95% CI 0.85-4.09, P = .12) and 1-year mortality (14.9% vs 7.7%, OR 2.10, 95% CI 1.38-3.18, P = .001). In-hospital and 1-year mortality was significantly higher in patients with BBB (eg, LBBB compared with QRS <120 milliseconds) (5.0% vs 1.9%, OR 2.71, 95% CI 1.49-4.94, P = .001, and 23.8% vs 7.7%, OR 3.74, 95% CI 2.72-5.13, P < .001). Analyzed as a continuous variable and after adjustment for validated prognosticators, QRS duration was an independent predictor of 1-year death (OR 1.11, 95% CI 1.06-1.16, P < .001) and death/myocardial infarction (OR 1.06, 95% CI 1.02-1.11, P = .003). However, when using clinically applicable QRS duration evaluation, only LBBB was an independent predictor of 1-year mortality (OR 1.93, 95% CI 1.28-2.90, P = .002). CONCLUSIONS: In patients presenting with a broad spectrum of suspected ACS, QRS prolongation particularly in the setting of LBBB-is an independent predictor of in-hospital and 1-year mortality. PMID- 20362718 TI - Plasma total cysteine and total homocysteine and risk of myocardial infarction in women: a prospective study. AB - BACKGROUND: Cysteine is a glutathione precursor, but is also a homocysteine byproduct. We prospectively evaluated relationships between fasting plasma concentrations of total cysteine and total homocysteine, and subsequent myocardial infarction (MI) in women. METHODS: Among 32,826 women who provided blood samples between 1989 and 1990, 239 were diagnosed with incident MI after blood collection, but before July 1998. Of these women, 144 had provided a postfast sample. We matched controls to cases 2:1 by age, cigarette smoking status, and month and fasting status at the time of blood collection. We used conditional logistic regression to adjust for confounding. RESULTS: Fasting total cysteine was positively related to MI risk in matching factor-adjusted analyses (rate ratio [RR] for highest vs lowest quartile 3.50 [95% CI 1.44-8.52]). However, after controlling for conventional risk factors of MI, it was not independently associated with risk (RR for highest vs lowest quartile 1.32 [95% CI 0.42-4.12, P trend = .10]). Fasting homocysteine was positively associated with MI risk; the multivariable adjusted RR for the highest versus the lowest quartile was 3.37 (95% CI 1.30-8.70, P trend = .014). CONCLUSIONS: Fasting plasma concentration of total homocysteine, but not total cysteine, was positively associated with MI risk. PMID- 20362719 TI - Evaluation of left ventricular ejection fraction in non-ST-segment elevation acute coronary syndromes and its relationship to treatment. AB - BACKGROUND: In-hospital assessment of left ventricular ejection fraction (LVEF) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is emphasized in current practice guidelines. There are limited data regarding the evaluation of LVEF and clinical characteristics and in-hospital management in the "real world." METHODS: Registries including the Canadian Acute Coronary Syndrome (ACS) I and II, Global Registry of Acute Coronary Events (main GRACE/expanded GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 13,703 NSTE-ACS patients across Canada between 1999 and 2008. Patients were stratified by in hospital LVEF measurement, and LVEF was categorized as normal, mildly, or moderately to severely impaired. We compared clinical characteristics, cardiac procedures, and clinical outcomes across these groups. Multivariable logistic regression identified factors independently associated with the assessment of LVEF. RESULTS: Overall, 8,116 patients (59.2%) had LVEF measurement, and of the 7,667 patients with available LVEF data, 4,470 (58.3%) had normal, 1,916 (25%) mildly impaired, and 1,281 (16.7%) moderately to severely impaired LVEF. Patients with LVEF assessment more frequently (all P < .001) underwent cardiac catheterization, percutaneous coronary intervention or coronary bypass surgery, and had higher (both P < .001) rates of myocardial (re) infarction and heart failure. In-hospital reinfarction, higher Killip class, abnormal biomarker, hospital stay >10 days, and on-site cardiac catheterization facility were independently associated with LVEF assessment. Despite increasing LVEF assessment over time (P for trend < .001), 31.2% of patients in the most recent registry (2008) had no in-hospital LVEF assessment. CONCLUSIONS: In-hospital LVEF assessment is not performed in many NSTE-ACS patients. The LVEF assessment, associated with increased use of evidence-based therapies and invasive cardiac procedures, was obtained more frequently in patients with myocardial (re) infarction, heart failure on presentation, and prolonged hospital stay. PMID- 20362720 TI - Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. AB - BACKGROUND: Elevated resting heart rate (RHR) is known to be associated with reduced survival but inconsistencies remain, including lack of significance in most studies of healthy women, lack of independence from systolic blood pressure (SBP) in some, and the suggestion that RHR is merely functioning as a marker of physical inactivity or other comorbidities. We aimed to clarify these inconsistencies. METHODS: We analyzed the effect of RHR on end points in the National FINRISK Study; a representative, prospective study using Cox proportional hazards model. Ten-thousand five-hundred nineteen men and 11,334 women were included, excluding those with preexisting coronary heart disease, angina, heart failure, or on antihypertensive therapy. RESULTS: The hazard ratios for cardiovascular disease (CVD) mortality for each 15 beats/min increase in RHR were 1.24 (1.11-1.40) in men and 1.32 (1.08-1.60) in women, adjusted for age, gender, total cholesterol, physical activity (categorical), SBP, body mass index, and high-density lipoprotein cholesterol. This relationship remained significant after exclusion of those with comorbidities and events occurring within first 2 years of observation. Relationship with coronary mortality was stronger and with total mortality was slightly weaker. Inclusion of nonfatal end points weakened the relationship. CONCLUSIONS: A strong, graded, independent relationship between RHR and incident CVD was demonstrated. This was consistent in healthy men and women. We have clarified that the relationship is independent of SBP and that the temporal sequence would be compatible with a causal relationship. New findings include independence from both a validated measure of physical activity and comorbidities and the demonstration of a stronger effect for fatal than nonfatal events, supporting increased arrhythmogenicity of one of the mechanisms. PMID- 20362721 TI - "Passive exercise" using whole body periodic acceleration: effects on coronary microcirculation. AB - BACKGROUND: The whole body periodic acceleration (WBPA) system has recently been developed as a "passive exercise" device by providing increased pulsatile shear stress for improvement of endothelial function. This study aimed to investigate the short-term effect of WBPA on coronary flow reserve (CFR) through transthoracic Doppler echocardiography (TTDE) in healthy subjects and patients with coronary artery disease (CAD). METHODS: This study consisted of 15 healthy subjects and 20 patients with CAD who underwent CFR examination before and immediately after WBPA. The flow velocity in the distal portion of the left anterior descending coronary artery (LAD) was measured with TTDE at baseline and during adenosine infusion. Coronary flow reserve was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. RESULTS: The WBPA treatment was completed in all 35 subjects without complications. There were no significant differences in heart rate and systolic blood pressure before and after WBPA. Whole body periodic acceleration increased CFR from 3.3 +/- 1.0 to 3.7 +/- 1.1 in the 35 subjects (P < .001). Coronary angiography showed significant LAD narrowing in 8 of the 20 CAD patients, but WBPA increased CFR from 2.4 +/- 0.4 to 2.7 +/- 0.5 in them as well (P < .01). CONCLUSIONS: This study demonstrates that WBPA improves CFR in healthy subjects and patients with CAD. PMID- 20362722 TI - Quality of life effects of automatic external defibrillators in the home: results from the Home Automatic External Defibrillator Trial (HAT). AB - BACKGROUND: Public access automatic external defibrillators (AEDs) can save lives, but most deaths from out-of-hospital sudden cardiac arrest occur at home. The Home Automatic External Defibrillator Trial (HAT) found no survival advantage for adding a home AED to cardiopulmonary resuscitation (CPR) training for 7,001 patients with a prior anterior wall myocardial infarction. Quality of life (QOL) outcomes for both the patient and spouse/companion were secondary end points. METHODS: A subset of 1,007 study patients and their spouse/companions was randomly selected for ascertainment of QOL by structured interview at baseline and 12 and 24 months after enrollment. The primary QOL measures were the Medical Outcomes Study 36-Item Short-Form psychological well-being (reflecting anxiety and depression) and vitality (reflecting energy and fatigue) subscales. RESULTS: For patients and spouse/companions, the psychological well-being and vitality scales did not differ significantly between those randomly assigned an AED plus CPR training and controls who received CPR training only. None of the other QOL measures collected showed a clinically and statistically significant difference between treatment groups. Patients in the AED group were more likely to report being extremely or quite a bit reassured by their treatment assignment. Spouse/companions in the AED group reported being less often nervous about the possibility of using AED/CPR treatment than those in the CPR group. CONCLUSIONS: Adding access to a home AED to CPR training did not affect QOL either for patients with a prior anterior myocardial infarction or their spouse/companion but did provide more reassurance to the patients without increasing anxiety for spouse/companions. PMID- 20362723 TI - Electronic health records and quality of care for heart failure. AB - BACKGROUND: Electronic health records (EHRs) are considered an important technology to improve the quality of health care, yet few data exist regarding their effect on delivery of evidence-based care in the outpatient setting. METHODS: IMPROVE HF is a prospective cohort study of 15,381 patients with HF or post myocardial infarction and left ventricular ejection fraction < or =35% cared for in 167 US outpatient cardiology practices. Baseline patient characteristics and quality data were collected by chart abstraction. To quantify care, 7 HF quality measures were assessed; practices with and without EHR were compared. RESULTS: Among practices, 52% had EHR systems (30% EHR-only; 22% both EHR and paper) and 48% paper-only systems. Conformity with indicated care for practices with EHR systems was modestly higher for 2 of 7 quality measures compared to those without. After controlling for patient and site characteristics, use of EHR was associated with improved delivery of 3 of 7 quality measures (angiotensin converting enzyme inhibitor/angiotensin receptor blocker, aldosterone antagonist, and HF education), similar care for 3 measures (beta-blocker, anticoagulation for atrial fibrillation, and cardiac resynchronization therapy), and worse for 1 measure (implantable cardioverter-defibrillator). CONCLUSIONS: These data are among the first to assess the potential influence of EHR on conformity with HF guidelines in the outpatient setting and suggest that EHR systems as currently deployed are associated with only modest differences in some, but not other, quality measures provided to HF patients compared with use of paper-only systems. PMID- 20362724 TI - Quantitative myocardial blush grade for the detection of cardiac allograft vasculopathy. AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) progressively compromises microvascular perfusion and function in heart transplantation (HTx)-recipients. The aim of our study was to investigate the ability of quantitative myocardial blush grade (MBG) to detect CAV. METHODS: In consecutive HTx-recipients (n = 72) who underwent surveillance cardiac catheterization, MBG was assessed visually and quantitatively, by analyzing the time course of contrast agent intensity rise. Hereby, the parameter G(max)/T(max) was calculated as the plateau of grey-level intensity (G(max)) divided by the time-to-peak intensity (T(max)). HTx-recipients and 18 healthy volunteers underwent cardiac magnetic resonance, to assess diastolic strain rates and myocardial perfusion reserve during pharmacologic hyperemia. RESULTS: Significant correlations were observed between G(max)/T(max) with perfusion reserve and with mean diastolic strain rates (r(2) = 0.68 and r(2) = 0.58, P < .001 for both). Visual and quantitative MBG using a cutoff value of G(max)/T(max) = 2.7/s yielded significantly higher accuracy than stenosis severity on coronary angiograms for the detection of impaired microvascular integrity as a surrogate marker for CAV (AUC = 0.78, SE = 0.06, 95% CI = 0.66 0.87 for lumen narrowing versus AUC = 0.91, SE = 0.03, 95%CI = 0.84-0.97 for G(max)/T(max); P < .01). Furthermore, quantitative MBG provided more robust prediction of survival (chi(2)= 14.0, P < .001), compared to visually estimated blush (chi(2)= 5.4, P = .02) and to coronary lumen narrowing assessment, (chi(2)= 4.8, P = .04). CONCLUSIONS: Quantification of MBG can be performed on coronary angiograms of HTx-recipients, and may help with the identification of early CAV in patients with impaired perfusion reserve but without angiographically evident atherosclerosis. PMID- 20362725 TI - Diagnostic and prognostic utility of electrocardiography for left ventricular hypertrophy defined by magnetic resonance imaging in relationship to ethnicity: the Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Left ventricular mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for left ventricular mass measurement. Ethnicity is believed to affect electrocardiographic (ECG) performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity. METHODS: Data were analyzed from 4,967 participants (48% men, mean age 62 +/- 10 years; 39% white, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 years for incident CVD. RESULTS: Thirteen traditional ECG-LVH criteria were assessed, and showed overall and ethnicity-specific low sensitivity (10%-26%) and high specificity (88%-99%) in diagnosing MRI-defined LVH. Ten of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared with whites (P = .02-.001). The sum of amplitudes of S wave in V(1), S wave in V(2), and R wave in V(5) (a MESA-specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared with prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (receiver operating characteristic area = 0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product, and Framingham-adjusted Cornell voltage predicted increased CVD risk (P < .05). CONCLUSIONS: Electrocardiography has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared with other ethnic groups. PMID- 20362726 TI - Predictors for short-term progressive heart failure death in New York Heart Association II patients implanted with a cardioverter defibrillator--the EVADEF study. AB - BACKGROUND: Sudden cardiac death (SCD) is the predominant cause of mortality in patients with mild heart failure (HF). This 2-year follow-up, multicenter, cohort study aimed to assess the extent to which implantable cardioverter defibrillators (ICDs), by reducing SCD, lead to predominant progressive HF death in mildly symptomatic HF patients at baseline in daily medical practice. METHODS: Between June 2001 and June 2003, 1,030 New York Heart Association II patients received an ICD in 22 French centers. Sudden cardiac death and progressive HF mortality rates were assessed using competing risk methodology, and predictors for progressive HF at baseline were tested in a multivariate regression model. RESULTS: During a mean follow-up of 22 +/- 6 months, 114 deaths occurred: 12 (10.5%) due to SCD and 52 (45.6%) due to progressive HF (24-month cause-specific mortality rates of 1.2% [95% CI 0.6-1.9] and 5.4% [95% CI 4.0-6.8], respectively). Diuretics use (hazard ratio [HR] 2.8, 95% CI 1.5-5.5, P = .002), history of atrial fibrillation (HR 2.09, 95% CI 1.2-3.65, P = .01), and low ejection fraction (HR 2.7, 95% CI 1.4 4.8, P = .0008) were independent predictors for progressive HF death, whereas beta-blocker therapy was a protector (HR 0.6, 95% CI 0.3-0.9, P = .04). Half of the patients (48%) who died from progressive HF within 2 years of ICD implant initially presented with enlarged QRS (> or =120 milliseconds). CONCLUSIONS: Because of ICD efficiency, progressive HF is the main cause of death within 2 years of implant, although these patients are only mildly symptomatic at implantation. In addition to optimal pharmacologic therapy, these results raise the question of systematically implanting ICDs with cardiac resynchronization therapy in patients with electrical asynchronism at baseline. PMID- 20362727 TI - Predicting left atrial thrombi in atrial fibrillation. AB - BACKGROUND: The aim of the study was to determine whether CHADS(2) score is predictive of left atrial appendage thrombus (LAAT) in nonvalvular atrial fibrillation (AF). Strategies for effective stroke prevention in AF require tools capable of identifying those patients at greatest risk for embolization of LAAT and most likely to benefit from warfarin. Nearly half of strokes in AF are due to noncardioembolic mechanisms for which antiplatelet therapy would be more appropriate. Previous attempts to develop such tools have been limited by including patients without proven cardioembolism. METHODS: Nonanticoagulated, nonvalvular AF patients with (cases) or without (controls) LAAT by transesophageal echocardiography were identified using Mayo Clinic Echocardiography and Cardioversion Unit Databases (Rochester, MN). Type and duration of AF, CHADS(2) score, and echocardiography measures were compared to determine variables predictive of LAAT. RESULTS: The CHADS(2) score was significantly higher for cases (n = 110, mean +/- SD 2.8 +/- 1.6) compared to controls (n = 387, 1.6 +/- 1.3). By multivariate analysis, independent predictors of LAAT included heart failure (HR 5.78, P < 0001), prior stroke/transient ischemic attack (HR 3.94, P < .0001), diabetes mellitus (HR 1.98, P = .015), permanent AF (HR 3.02, P < .05), AF duration (HR 2.24, P < .05), and spontaneous echocardiographic contrast (HR 4.35, P = .005). Using these elements, a new scoring system provided cleaner case-control separation (C-index 0.90) and higher predictive power compared to CHADS(2) (C-index 0.71). CONCLUSIONS: The CHADS(2) score predicts the presence of LAAT in AF patients. Some, but not all, variables within this score are predictive of LAAT. By including only echo and clinical variables predictive of LAAT, our novel scoring system better identified those AF patients at greatest cardioembolic risk. PMID- 20362728 TI - The outcome of primary percutaneous coronary intervention for stent thrombosis causing ST-elevation myocardial infarction. AB - BACKGROUND: There are very few scientific data about the effectiveness of primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) due to stent thrombosis (ST). The purpose of the present study is to investigate the efficacy and outcome of primary PCI for STEMI due to ST in the largest consecutive patient population with ST reported to date. METHODS: A total of 2,644 consecutive STEMI patients undergoing primary PCI were retrospectively enrolled into the present study. The primary end point of this study was successful angiographic reperfusion defined as postprocedural Thrombolysis In Myocardial Infarction grade III flow. The secondary end points were cardiovascular death and reinfarction. RESULTS: Stent thrombosis was the cause of STEMI in 118 patients (4.4%). In patients with ST, angiographic success (postprocedural Thrombolysis In Myocardial Infarction grade III flow) was worse than in patients with de novo STEMI (76.3% vs 84.8%, P = .01). Patients with ST had significantly higher incidence of in-hospital cardiovascular mortality than patients with de novo STEMI (10.2% vs 5.3%, P = .02). In-hospital reinfarction rate was similar in both groups. In addition, long-term (mean 22 months) cardiovascular mortality and reinfarction rates were significantly higher in patients with ST compared with those without (17.4% vs 10.5%, P = .02 and 15.6% vs 9.5%, P = .03, respectively). CONCLUSIONS: Primary PCI for treatment of ST is less effective, and these patients are at increased risk for in-hospital and long term mortality compared with patients undergoing primary PCI due to de novo STEMI. PMID- 20362729 TI - Gender differences in adverse outcomes after contemporary percutaneous coronary intervention: an analysis from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) percutaneous coronary intervention registry. AB - BACKGROUND: Prior studies have shown a relationship between female gender and adverse outcomes after percutaneous coronary interventions (PCIs). Whether this relationship still exists with contemporary PCI remains to be determined. METHODS: We evaluated gender differences in clinical outcomes in a large registry of contemporary PCI. Data were prospectively collected from 22,725 consecutive PCIs in a multicenter regional consortium (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) between January 2002 and December 2003. The primary end point was in-hospital all-cause mortality; other clinical outcomes evaluated included in-hospital death, vascular complications, transfusion, postprocedure myocardial infarction, stroke, and a combined major cardiovascular adverse event (MACE) end point including myocardial infarction, death, stroke, emergency coronary artery bypass grafting, and repeated PCI at the same site. Independent predictors of adverse outcomes were identified using multivariate logistic regression analysis. RESULTS: Compared with men, women were older, had a higher prevalence of comorbidities, and had a significantly higher frequency of adverse outcomes after PCI. After adjustment for baseline demographics, comorbidities, clinical presentation, and lesion characteristics, female gender was associated with an increased risk of in-hospital death, vascular complication, blood transfusion, stroke, and MACE. The relationship between female gender and increased risk of death and MACE was no longer present after further adjustment for kidney function and low body surface area. CONCLUSIONS: Differences in mortality rates between men and women no longer exist after PCI. However, our data suggest that technological advancements have not completely offset the relationship between gender and adverse outcomes after PCI. PMID- 20362731 TI - Preoperative pulmonary function and mortality after cardiac surgery. AB - BACKGROUND: The aim of the study was to examine the relationship between preoperative pulmonary function and outcomes after cardiac surgery. METHODS: We performed preoperative pulmonary function tests (PFTs) in 1,169 patients undergoing cardiac surgery at the Minneapolis Veterans Affairs Medical Center. Airway obstruction was defined as forced expiratory volume in 1 minute (FEV(1)) to forced vital capacity ratio <0.7. RESULTS: Of the 1,169 patients, 483 (41%) had a prior history of chronic obstructive pulmonary disease (COPD). However, 178 patients with a history of COPD had no airway obstruction on PFT. Conversely, 186 patients without a COPD history had airway obstruction on PFT. Thus, PFT results helped reclassify the COPD status of 364 patients (31%). Operative mortality was 2% in patients with no or mild airway obstruction versus 6.7% in those with moderate or severe obstruction (ie, FEV(1) to forced vital capacity ratio <0.7 and FEV(1) <80% predicted). Postoperative mortality was higher (odds ratio 3.2, 95% CI 1.6-6.2, P = .001) in patients with moderate or severe airway obstruction and in patients with diffusing capacity of the lung for carbon monoxide <50% of predicted (odds ratio 4.9, 95% CI 2.3-10.8, P = .0001). Notably, mortality risk was 10x higher (95% CI 3.4-27.2, P = .0001) in patients with moderate or severe airway obstruction and diffusing capacity of the lung for carbon monoxide <50% of predicted. CONCLUSIONS: These data show that PFT before cardiac surgery reclassifies the COPD status of a substantial number of patients and provides important prognostic information that the current risk estimate models do not capture. PMID- 20362730 TI - Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents. AB - BACKGROUND: Whether low-molecular-weight heparin (LMWH) is superior to unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) remains unclear. METHODS: A total of 3,372 STEMI patients who underwent primary PCI with DESs received either LMWH (n = 1,531 patients, subcutaneous enoxaparin 1 mg/kg, bid for 3-5 days plus reduced dose of UFH [50 U/kg] during PCI) or UFH alone (n = 1,841 patients, intravenous bolus injection of 5,000 U, followed by 24,000 U/d infusion for at least 48 hours). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared. RESULTS: The incidences of major and minor bleeding events were similar between the 2 groups. Multivariable Cox regression analysis showed that LMWH group had lower incidences of cardiac death (adjusted odds ratio [OR] 0.55, 95% CI 0.39-0.77, P < .001), total death (adjusted OR 0.50, 95% CI 0.37-0.68, P < .001), and total major adverse cardiac events (adjusted OR 0.77, 95% CI 0.62 0.95, P = .017) at 8 months as compared with UFH group. Similar results were obtained across different subgroups including different DESs, age, and sex. CONCLUSIONS: The LMWH enoxaparin combined with reduced dose of UFH (50 U/kg) administration as an adjunctive antithrombotic therapy in STEMI patients undergoing primary PCI with DESs seems to be safe and efficacious. However, randomized clinical trials are needed to confirm this conclusion. PMID- 20362732 TI - Ethnic differences in aortic valve thickness and related clinical factors. AB - BACKGROUND: Prior studies suggest that the causes of calcific aortic valve (AV) disease involve chronic inflammation, lipoprotein levels, and calcium metabolism, all of which may differ among race-ethnic groups. We sought to determine whether AV thickness differs by race-ethnicity in a large multiethnic population-based cohort. METHODS: The Northern Manhattan Study includes stroke-free community based Hispanic (57%), non-Hispanic black (22%), and non-Hispanic white (21%) participants. The relation between AV thickness on transthoracic echocardiography and clinical risk factors for atherosclerosis was evaluated among 2,085 participants using polytomous logistic regression models. Aortic valve thickness was graded in 3 categories (normal, mild, and moderate/severe) based on leaflet thickening and calcification. RESULTS: Mild AV thickness was present in 44.4% and moderate/severe thickness in 5.7% of the cohort, with the lowest frequency of moderate/severe thickness seen particularly among Hispanic women. In multivariate models adjusting for age, sex, race-ethnicity, body mass index, hypertension, coronary artery disease, blood glucose, and high-density lipoprotein cholesterol, Hispanics had significantly less moderate/severe AV thickness (odds ratio 0.43, 95% CI 0.25-0.73) than non-Hispanic whites. Men were almost 2-fold as likely to have moderate/severe AV thickness compared with women (odds ratio 1.96, 95% CI 1.24-3.10). CONCLUSIONS: In this large multiethnic population-based cohort, there were ethnic differences in the degree of AV thickness. Hispanic ethnicity was strongly protective against AV thickness. This effect was not related to traditional risk factors, suggesting that unmeasured factors related to Hispanic ethnicity and AV thickness may be responsible. PMID- 20362733 TI - Disseminated Mycobacterium avium-intracellulare complex infection. PMID- 20362734 TI - Safety of concomitant use of proton pump inhibitors and clopidogrel. PMID- 20362736 TI - C1 inhibitor therapy and hereditary angioedema. PMID- 20362738 TI - Recommendations on the drug treatment of psychosis in Parkinson's disease. PMID- 20362740 TI - A speckled chest radiograph. PMID- 20362741 TI - A case of hypercalcemia and scabies. PMID- 20362742 TI - Emphysematous pyelonephritis caused by Candida tropicalis. PMID- 20362743 TI - Recalcitrant Grysbovski's keratoacanthomas with good response to cimetidine. PMID- 20362744 TI - Sunshine: clinical friend or foe? PMID- 20362745 TI - In praise of older doctors: a paean for experience. PMID- 20362746 TI - Toxic exanthems in the adult population. AB - Frequently the internist is confronted with the nonspecific exanthematous eruption. While often a sign of a benign and self-limiting process, an exanthem also might herald the development of a more severe systemic syndrome. Infections, immune-mediated processes, drug reactions, a neoplasm, and familial syndromes with poor prognoses might all manifest initially with an exanthem. A thorough history and complete physical examination should be performed on all patients who present with an exanthem. Characterization of the exanthem morphology, other physical examination findings, and review of systems can help guide laboratory testing and ensure prompt diagnosis and early treatment of potentially life threatening conditions. This article provides a brief overview of the conditions that must be considered in the evaluation of an ill patient with an exanthem. PMID- 20362748 TI - Spotted fever: meningococcal disease and petechiae. PMID- 20362749 TI - It started with a rash. PMID- 20362747 TI - Does chronic microaspiration cause idiopathic pulmonary fibrosis? AB - Idiopathic pulmonary fibrosis is a diffuse fibrotic lung disease of unknown etiology with no effective treatment. Emerging data support a role for chronic microaspiration (ie, subclinical aspiration of small droplets) in the pathogenesis and natural history of idiopathic pulmonary fibrosis. However, the precise relationship between chronic microaspiration and idiopathic pulmonary fibrosis remains unknown. Gastroesophageal reflux, a presumed risk factor for microaspiration, has been strongly associated with idiopathic pulmonary fibrosis with an estimated prevalence of up to 90%. This review aims to describe the relationship between chronic microaspiration and idiopathic pulmonary fibrosis by laying out the clinical and biologic rationale for this relationship and exploring the scientific evidence available. The gaps in our current understanding of the diagnosis of chronic microaspiration and idiopathic pulmonary fibrosis and the ongoing uncertainties in management and treatment will be highlighted. Defining the role of chronic microaspiration in idiopathic pulmonary fibrosis is essential as it has potential clinical, pathobiological, and treatment implications for this deadly disease. PMID- 20362750 TI - A blistering rash. PMID- 20362751 TI - Periumbilical pain. PMID- 20362752 TI - Optimization of clinical breast examination. AB - BACKGROUND: Breast examination is necessary for evaluation of the 8% to 17% of cancers missed by mammograms, but it is being done less often and less effectively. To improve the use of breast examination, we tested whether a technique to focus attention could improve the call rate (the percent of examinations leading to further evaluation), a measure of quality, without retraining in examination technique. METHODS: Clinicians were randomized to complete 1 of 2 dedicated, de-identified forms after routine breast examination: a long form intended to focus attention by requesting general breast descriptors along with clinical information and breast examination findings (10 clinicians recorded 964 examinations) or a short form recording only clinical information and examination findings (11 clinicians recorded 558 examinations). There was no technique retraining. Study call rates were compared with historical controls (298 breast examinations by 16 clinicians). RESULTS: The call rates by the study groups of clinicians were similar, but the call rate using either form (8.3%) was significantly higher than the call rate in the preceding year when no dedicated form was used (4.7%; P=.031), suggesting a Hawthorne effect in which altering conditions of data collection (using the dedicated forms) functioned as an independent variable. Surveillance, Epidemiology, and End Results data predicted 3.4 cancers in all 1822 patients; 4 cancers were found. CONCLUSION: Breast examination call rate doubled when attention was focused on examination results using a dedicated form, and we found the anticipated cancers. Breast examination quality can be improved by focusing clinician attention without retraining in technique. PMID- 20362753 TI - Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations? AB - BACKGROUND: Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation. METHODS: Plasma concentrations of 25-hydroxyvitamin D(3) were determined by radioimmunoassay in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4+/-6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation. RESULTS: On univariate analyses, low 25-hydroxyvitamin D(3) levels were inversely correlated with asymmetric dimethylarginine concentrations, high sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D(3) levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D(3) levels. On multiple linear analysis, both asymmetric dimethylarginine (beta=-0.19, P=.003) and high-sensitivity C reactive protein (beta=-0.14, P=.03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations; other significant correlates were male gender (beta=0.19, P=.003), calcium levels (beta=0.14, P=.03), and use of angiotensin-converting enzyme inhibitor (beta=-0.17, P=.007). CONCLUSION: Low 25-hydroxyvitamin D(3) levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk. PMID- 20362754 TI - Low blood pressure and depressive symptoms among Chinese older subjects: a population-based study. AB - BACKGROUND: The relationships between blood pressure and depression are unclear. There are inconsistent reports of an association between low blood pressure and depressive symptoms. METHODS: In a population-based sample of 2611 Chinese older adults aged 55 years and above, including participants with treated (n=1088), untreated (n=545), or no hypertension (n=978), depressive symptoms were determined by the 15-item Geriatric Depression Scale (> or =5), and current systolic blood pressure and diastolic blood pressure measurements were used to classify participants into high, normal, and low blood pressure groups. Estimates of association were adjusted for confounding by use of antihypertensive and depressogenic drugs and other covariables in hierarchical regression analyses. RESULTS: Systolic blood pressure and diastolic blood pressure were negatively associated with Geriatric Depression Scale scores, independent of other variables. Low systolic blood pressure (odds ratio [OR] 1.54; 95% confidence interval [CI], 1.07-2.22), low diastolic blood pressure (OR 1.67; 95% CI, 0.98 2.85), and low systolic blood pressure or diastolic blood pressure (or both) (OR 1.55; 95% CI, 1.10-2.19) were independently associated with depressive symptoms. The associations with depressive symptoms were particularly observed for low systolic blood pressure (OR 2.13; 95% CI, 1.13-4.03) among treated hypertensive participants, and low diastolic blood pressure (OR 2.42; 95% CI, 1.26-4.68) among untreated or nonhypertensive participants. CONCLUSION: Low blood pressure was independently associated with depressive symptoms in both older subjects who were treated for hypertension and those who were not. PMID- 20362755 TI - Coronary heart disease and stroke risk in patients with psoriasis: retrospective analysis. AB - BACKGROUND: Past studies suggest an association between psoriasis and the risk of developing coronary heart disease. The objectives of this study were to estimate the 10-year risks of coronary heart disease and stroke in patients with moderate to severe psoriasis, to compare risks between patients and the general population, and to determine whether risk profiles are affected by disease severity. METHODS: Data were pooled from patients with moderate to severe psoriasis (Psoriasis Area and Severity Index [PASI] score> or =10) who were enrolled in Phase II (M02-528) or Phase III trials (Comparative Study of HUMIRA vs Methotrexate vs Placebo In PsOriasis PatieNts[CHAMPION], Randomized Controlled EValuation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis TriAL[REVEAL]) evaluating adalimumab. Risks of coronary heart disease and stroke were estimated using the Framingham risk score algorithm and a stroke risk function based on the Framingham Heart Study cohorts. To compare risks between patients with psoriasis and the general population, average population risks were imputed on the basis of age and gender. Wilcoxon rank-sum tests evaluated risk differences between patients with psoriasis and the general population and between patients with moderate psoriasis and patients with severe psoriasis. RESULTS: A total of 1591 patients were identified, including 1082 patients with PASI scores> or =10 and < or = 20 and 509 patients with PASI scores>20. Patients with PASI scores from 10 to 20 and PASI scores>20 had similar 10-year risks of coronary heart disease (12.3% and 12.2%; P=.49) and stroke (8.3% and 8.7%; P=.28). Compared with the general population, 10-year risks of patients with psoriasis were 28% greater for coronary heart disease (P<.001) and 11.8% greater for stroke (P=.02). CONCLUSION: Patients with moderate to severe psoriasis had increased risks of coronary heart disease and stroke compared with the general population. PMID- 20362756 TI - Systematic review of the symptom burden, quality of life impairment and costs associated with peptic ulcer disease. AB - BACKGROUND: Management of peptic ulcer disease has improved over the past few decades. However, the widespread use of nonsteroidal anti-inflammatory drugs and low-dose acetylsalicylic acid means that the burden of peptic ulcer disease remains a relevant issue. METHODS: We systematically searched PubMed and EMBASE for articles published 1966-2007 that reported symptoms, impairment of well-being or health-related quality of life, and costs associated with peptic ulcer disease. RESULTS: Thirty studies reported the prevalence of patient-reported gastrointestinal symptoms in individuals with endoscopically diagnosed symptomatic peptic ulcer disease. Average prevalence estimates, weighted by sample size, were 81% (95% confidence interval [CI], 77%-85%) for abdominal pain (11 studies), 81% (95% CI, 76%-85%) for pain specifically of epigastric origin (14 studies), and 46% (95% CI, 42%-50%) for heartburn or acid regurgitation (11 studies). On average, 29% (95% CI, 25%-34%) of patients with peptic ulcer disease presented with bleeding, often as the initial symptom (11 studies). Patients with peptic ulcer disease had significantly lower health-related quality of life than the general population, as measured by the Psychological General Well-Being index (P <.05; 7 studies) and the Short-Form-36 questionnaire (P <.05; 2 studies). Direct medical costs of peptic ulcer disease based on national estimates from several countries were USD163-866 per patient. The most costly aspects of peptic ulcer disease management were hospitalization and medication. Complicated peptic ulcer disease is particularly costly, estimated to be USD1883-25,444 per patient. CONCLUSION: Peptic ulcer disease significantly impairs well-being and aspects of health-related quality of life, and is associated with high costs for employers and health care systems. PMID- 20362757 TI - Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity. AB - BACKGROUND: Gabapentin is frequently used as an analgesic in patients with chronic kidney disease. Although gabapentin is well known for its favorable pharmacokinetics, it is exclusively eliminated renally, and patients with chronic kidney disease are at risk for toxicity. Existing literature on such risk is lacking. METHODS: We examined the Mayo Clinic Rochester database from 1998 to 2007 in patients with serum gabapentin measurements and known medical outcomes. A total of 729 patients were stratified according to their estimated glomerular filtration rate: group I, 126 individuals with estimated glomerular filtration greater than 90 mL/min/1.72 mm(2) [corrected] ; group II, 594 individuals with estimated glomerular filtration less than 90 mL/min/1.72 mm(2) [corrected] without dialysis; group III, 9 individuals with chronic dialysis. RESULTS: Patients in groups II and III had higher serum gabapentin levels (8.39+/-0.32 microL/mL and 58.8+/-10.22 microL/mL, respectively) than in group I (5.52+/-0.32 microL/mL, P<.01). Toxicity occurred exclusively in groups II (5.56%) and III (77.8%); toxic manifestations were more severe in group III than in group II. Elderly individuals with multiple comorbidities were overrepresented in those with toxic manifestations. Gabapentin toxicity was suspected initially in only 41.5% of symptomatic cases. CONCLUSION: Gabapentin toxicity in patients with chronic kidney disease is underrecognized. Patients with chronic kidney disease often receive inappropriately high gabapentin dosage for their kidney function, occasioning overt toxicity; advanced age and comorbidity predispose these patients for toxicity. Heightened awareness of such preventable risk, amid the chronic kidney disease epidemic, would be cost-effective and improve healthcare quality. PMID- 20362759 TI - Type 2 diabetes: assessing the relative risks and benefits of glucose-lowering medications. AB - The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications. PMID- 20362758 TI - The relationship between retinal microvascular abnormalities and coronary heart disease: a review. AB - Heart disease remains the leading cause of death in the United States despite decades of advancement in its diagnosis and treatment. Because of the limitations of traditional risk stratification for heart disease, evaluation of the retinal vasculature has been proposed as an easily and safely measured adjunct to commonly used screening methods. This article provides a comprehensive review of the literature concerning the relationships between retinal microvascular abnormalities and coronary heart disease. We outline details of the most recent large epidemiologic studies and discuss their potential implications for clinical practice. Finally, we propose a change to the current guidelines regarding the screening of "low-risk" women, a group that is often failed by traditional evaluation algorithms. PMID- 20362760 TI - Experience with faculty supervision of an electronic resident sign-out system. PMID- 20362761 TI - Readers' roundtable. PMID- 20362762 TI - Prosthodontic treatment of a patient with bisphosphonate-induced osteonecrosis of the jaw using a removable dental prosthesis with a heat-polymerized resilient liner: a clinical report. AB - Bisphosphonate-induced osteonecrosis of the jaws (BONJ) is reported frequently in patients receiving oral or intravenous bisphosphonates. To minimize potential complications, dental treatment must be performed with care. There are invasive and noninvasive treatment options for patients with active BONJ or a history of this complication. This clinical report describes the prosthodontic treatment of a patient who developed BONJ after receiving intravenous bisphosphonates (pamidronate). Because of the recurrent incidence of BONJ, noninvasive prosthetic therapy with telescopic overdentures and a heat-polymerized resilient liner was provided. After 2 years, there were no biological or technical complications. PMID- 20362763 TI - Analysis of three-dimensional distortion of two impression materials in the transfer of dental implants. AB - STATEMENT OF PROBLEM: In dental implant restorations, a lack of passivity may be associated with mechanical failure. Passivity can be compromised during impression making. PURPOSE: The purpose of this study was to compare the distortion of mechanically mixed polyether and hydrophilic addition silicone impression materials, and to evaluate the effect of intercoping distance on distortion. MATERIAL AND METHODS: Twenty impressions (10 polyether and 10 silicone) were made from a single mandibular definitive cast with 5 abutment analogs using standardized laboratory and technique protocols. The direct impression technique and mechanical mixing were used. A precision measuring machine established spatial coordinates of the impression copings in 3 dimensions, with the operator blinded to materials. Linear distances (concentricity) and angular inclinations (perpendicularity, parallelism) were calculated to measure impression distortion relative to the positions/angulations of the implants in the definitive cast. Distortion differences between materials and implant intercoping distances were tested using 2-factor ANOVA with an interaction term. A Bonferroni 2-sided test was used (alpha=.05). RESULTS: No significant difference was found between the impression materials for parallelism (P=.91) and concentricity (P=.85). For perpendicularity, the silicone material had an average of 0.643 degrees less distortion (P=.004). With respect to intercoping distances, no significant differences were found for perpendicularity (P=.234), parallelism (P=.114), or concentricity (P=.346). An interaction term for material and coping distance was not significant. CONCLUSIONS: Hydrophilic addition silicone and polyether impression materials have similar distortion effects for transfer procedures when using the direct impression technique and machine mixing. Silicone demonstrated superiority for perpendicularity distortion, though of a magnitude unlikely to have clinical significance. PMID- 20362764 TI - The effect of zirconia surface treatment on flexural strength and shear bond strength to a resin cement. AB - STATEMENT OF PROBLEM: Despite the expanded applications for zirconia in restorative dentistry, there is no clear recommendation in the literature regarding surface treatment before bonding. PURPOSE: The purpose of this study was to evaluate the effect of mechanical surface treatment of yttria-partially stabilized zirconia on its flexural strength and the effect of mechanical and chemical surface treatments on its bond strength to a resin cement. MATERIAL AND METHODS: For flexural strength evaluation, zirconia bars (4 x 5 x 40 mm) were prepared from zirconia blocks, finished using a diamond rotary cutting instrument, sintered, then assigned into 4 groups: (1) control (no treatment), (2) airborne-particle abrasion, (3) silicoating, and (4) wet hand grinding. After storage for 24 hours at 37 degrees C, flexural strength was determined using a 3 point bending test, and the results were analyzed using 1-way ANOVA (alpha=.05). For shear bond strength evaluation, zirconia rods (2.5 x 3 mm) were prepared from zirconia blocks, sintered, and assigned into 16 groups. Each group underwent a combination of the following mechanical and chemical treatments. Mechanical treatment included: (1) control (no treatment), (2) airborne-particle abrasion, (3) silicoating, or (4) wet hand grinding. Chemical treatment included: (1) control (no treatment), (2) acid etching followed by silanation, (3) silanation only, or (4) application of zirconia primer. Dentin specimens were prepared from extracted molars stored in 0.5% chloramine-T. Zirconia rods were bonded to dentin using a resin cement (Multilink Automix), then light polymerized. After storage, the specimens were loaded to failure with the notched shear bond test method in a universal loading apparatus. For artificial aging analysis, the groups that achieved the highest bond strength values were duplicated, stored at 37 degrees C and 100% humidity for 90 days, and thermal cycled before being loaded to failure. Results were analyzed using 2-way ANOVA (alpha=.05). RESULTS: Airborne-particle abrasion and hand grinding significantly increased flexural strength. The highest shear bond strength values were achieved for the following groups: silicoated + silanated > hand ground + zirconia primer > airborne-particle abraded + silanated > zirconia primer > airborne-particle abraded + zirconia primer. Artificial aging resulted in significantly lower shear bond strength for the silicoated/silanated and the zirconia primer groups. CONCLUSIONS: Mechanical modification of the surface increased the flexural strength of Y-TZP. The resin bond to Y-TZP was improved by surface treatment. A combination of mechanical and chemical conditioning of the zirconia surface was essential to develop a durable resin bond to zirconia. PMID- 20362765 TI - Effect of different finishing techniques for restorative materials on surface roughness and bacterial adhesion. AB - STATEMENT OF PROBLEM: The formation of biofilm and bacterial accumulation on dental materials may lead to the development of gingival inflammation and secondary caries. PURPOSE: The purpose of this study was to examine the effect of different surface finishing and polishing methods on surface roughness and the adhesion of S. mutans bacteria to 2 new-generation indirect composite resins, 1 direct composite resin, and 1 ceramic material. MATERIAL AND METHODS: Forty specimens (10 x 10 x 2 mm) of each material, indirect composite resins (SR Adoro, Estenia), direct composite resin (Tetric), and a ceramic material (VITABLOCS Mark II), were fabricated. Specimens were divided into 4 groups (n=10) that were treated with 1 of the following 4 surface finishing techniques: diamond rotary cutting instrument, sandpaper discs (Sof-Lex), silicone-carbide rubber points (Shofu), or a felt wheel with diamond paste. Surface roughness was measured with a profilometer. Test specimens were covered with artificial saliva and mucin to produce pellicle. Bacterial suspension (10(9) CFU/ml) was then added to the pellicle-coated specimens, and bacterial adhesion was determined using a confocal laser microscope and image analyzing program. Data were analyzed with 2-way ANOVA, followed by Tukey HSD test, Pearson correlation, and regression analysis (alpha=.05). RESULTS: The highest surface roughness values were recorded in SR Adoro and diamond rotary cutting instrument groups. The lowest vital S. mutans adhesion was seen in the ceramic group and in SR Adoro indirect composite resin (P<.05). CONCLUSIONS: Bacterial adhesion to indirect composite resin materials differed from that to ceramic material after surface treatments. A positive correlation was observed between surface roughness and the vital S. mutans adhesion. PMID- 20362766 TI - Accuracy of the newly formulated vinyl siloxanether elastomeric impression material. AB - STATEMENT OF PROBLEM: A newly formulated vinyl siloxanether elastomeric impression material is available, but there is little knowledge of its accuracy in relation to existing materials. PURPOSE: The purpose of this in vitro study was to assess the accuracy of disinfected vinyl siloxanether impressions and compare the accuracy to a common vinyl polysiloxane and a polyether impression system. MATERIAL AND METHODS: Impressions were made from a modified dentoform master model containing a simulated crown preparation. Dimensional changes (mm) between the master model and working casts (type IV gypsum) were assessed. The following were evaluated: vinyl polysiloxane in a 1-step, dual-viscosity technique (VPS Dual), polyether as monophase material (PE Mono), and vinyl siloxanether in a 1-step, dual-viscosity (VSE Dual), and monophase technique (VSE Mono). Measurements of the master model and working casts, including anteroposterior (AP) and cross-arch (XA) dimensions, were made with a measuring microscope. The simulated crown preparation was measured in mesiodistal (MDG, MDO), buccolingual (BLG, BLO), and occlusogingival dimensions (OGL, OGB). Disinfection involved immersion for 10 minutes in potassium peroxomonosulfate, sodium benzoate, tartaric acid solution, or no disinfection (control) (n=8). A multivariate GLM statistical approach (MANOVA) was used to analyze the data (alpha=.05). Pearson's correlation test was used for related dimensions. RESULTS: The AP and XA dimensions of working casts were larger than the master for the disinfected condition and control. Whether disinfected or not, the working dies were shorter in height (OGB, OGL), larger in the buccolingual dimension (BLO, BLG), somewhat larger in the MDO dimension, and somewhat smaller in the MDG dimension compared to the prepared tooth of the master model, resulting in an irregular or oval profile. There were significant differences among the impression systems for each dimension except AP. Differences between the disinfected and nondisinfected conditions were significant (P=.03) with respect to dimensions of the gypsum working cast, but not for dimensions of the working die (P=.97). In general, differences relative to the master were small and of minor clinical significance considering marginal gaps of crowns smaller than 150 100 mum are considered clinically acceptable. CONCLUSIONS: VSE monophase impressions and VSE dual-viscosity impressions demonstrated acceptable accuracy for clinical use with immersion disinfection, since the results for VSE were comparable to the results for PE and VPS materials, and the differences as compared to the master model were small. PMID- 20362767 TI - Comparison of clasp retention on enamel and composite resin-recontoured abutments following repeated removal in vitro. AB - STATEMENT OF PROBLEM: Loss of prosthetic retention over time is a concern with removable prostheses. Use of composite resin to modify an abutment contour receiving a removable partial denture clasp may offer a reasonable, less invasive method of improving removable prosthesis retention. PURPOSE: The purpose of this study was to evaluate the removal force of clasps over composite resin recontoured abutments during a simulated 4 years of service. MATERIAL AND METHODS: Twenty first mandibular premolars were selected to form 2 groups of specimens (n=5) resembling a tooth-supported edentulous space. A packable composite resin (Filtek P60) was used to create a 0.25-mm undercut on the buccal abutment surfaces of the composite resin group. Teeth in the natural abutment group were mounted in angulation to produce 0.25-mm undercuts on the buccal surfaces. The chrome-cobalt framework consisted of 2 individually fabricated T clasps. Both groups were subjected to 4500 cycles of repeated removal using a small shaker. Removal forces were recorded before the repeated removal test (T(0)), after 500 and 1000 cycles, and at 1000-cycle intervals thereafter. The mean values of forces between the 2 groups were compared at each stage using the Mann-Whitney test (alpha=.05). RESULTS: No debonding occurred during the test. At T(0), the highest and lowest force values were observed in the composite resin group (3.75 N and 17.5 N, respectively). There was a significant difference between the removal forces of the 2 groups after 500 cycles and at test completion (P=.008). Retention loss was 3 times greater in the composite resin group than in the natural abutments group (53.65% vs. 15.80%). CONCLUSIONS: Within the limitations of the study, removal forces of the composite resin recontoured abutments were threefold less than those of natural abutments after 4 years of simulated service. PMID- 20362768 TI - Effect of surface treatments and cyclic loading on the bond strength of acrylic resin denture teeth with autopolymerized repair acrylic resin. AB - STATEMENT OF PROBLEM: Fracture of denture teeth from the denture base is a common problem associated with dental prostheses. Fractured tooth surfaces treated with chemical agents and mechanical features have the potential for improved repair strength. PURPOSE: The purpose of this study was to compare bond strengths of denture teeth to autopolymerized repair acrylic resin after various surface treatments, before and after cyclic loading. MATERIAL AND METHODS: Mandibular lateral incisor denture teeth were selected and ground on the ridge-lap portion using a standardized jig. Specimens with a ground surface were used as controls. The experimental groups included: ground plus airborne-particle abraded, ground plus diatoric recess, and ground plus an experimental bonding agent. The teeth were affixed by an autopolymerized repair acrylic resin to denture bases. Specimens (n=10) were subjected to compression testing (5 mm/min) at a 135-degree angle, before and after 14,400 loading cycles at 2 Hz and 22 N. Peak load to dislodgement was recorded and statistically analyzed (2-way ANOVA, Tukey HSD, alpha=.05). The specimens were then examined using x10 magnification, and fractures were categorized as adhesive, cohesive, or mixed. RESULTS: The mean bond strengths ranged from 26.3 N to 44.2 N. There were no significant differences in fatigue versus nonfatigue strength values within each group (P=.244). Significant strength differences were found (P<.001) between the ground control, diatoric recess, and bonding agent groups. Microscopic examination revealed that the bonding agent group obtained the highest percentage of mixed type fractures. CONCLUSIONS: The use of a bonding agent and the placement of a diatoric recess in the denture tooth resulted in higher bond strengths than grinding alone. Cyclic loading had no significant impact on the bond strength of denture teeth to the autopolymerized repair acrylic resin. PMID- 20362769 TI - A surgical guide for craniofacial implant placement for an implant-retained auricular prosthesis. AB - Craniofacial implants provide excellent stability and retention for auricular prosthetic rehabilitation. Accurate location of implants is important to achieve optimal prosthetic results. This article describes an alternative procedure for fabricating an acrylic resin surgical template for craniofacial implant placement with the assistance of a 6-inch contour duplication gauge. PMID- 20362770 TI - A wax guide to measure the amount of occlusal reduction during tooth preparation in fixed prosthodontics. PMID- 20362771 TI - A technique for definitive cast fabrication. PMID- 20362772 TI - Maelstrom of change: back to the future. PMID- 20362773 TI - The Grand Challenges and nursing. PMID- 20362774 TI - "Medical history and epidemiology: their contribution to the development of public health nursing.". PMID- 20362775 TI - Evidence for a new paradigm of the ministry of parish nursing practice using the nursing intervention classification system. AB - A national study of parish nurses used the Nursing Intervention Classification (NIC) Use Survey (3rd Ed.) to characterize parish nursing practice. The study categorized NIC interventions based on frequency of use by parish nurses. The majority of nursing interventions focused on the Behavioral Domain, which supports psychosocial functioning and facilitates lifestyle changes and the Coping Assistance Class, which includes spiritual support. Data provides evidence to further understand what parish nurses do in their daily practice, as well as clarifies the complexity and scope of this specialty practice. Findings confirm that parish nursing is a specialty nursing practice as well as a ministry. Objective descriptions of parish nurse practice, including the identification of the most commonly used parish nurse interventions, will assist in providing direction for defining the role of the parish nurse and providing a basis for reviewing the current content of parish nurse curriculum. The database, which uses a standardized nursing language, also provides evidence for a new paradigm of the ministry of parish nursing practice that is intelligible to other nurses, policy makers, and funders. PMID- 20362776 TI - Toward a conceptual definition of frail community dwelling older people. AB - In order to be able to identify frail community-dwelling older people, a reliable and valid definition of the concept of frailty is necessary. The aim of this study was to provide an overview of the literature on conceptual and operational definitions of frailty, and to determine which definitions are most appropriate for identifying frail community-dwelling older people. Therefore, a computerized search was performed in the PubMed database, Web of Science and PsychInfo. A successful definition of frailty reflects a multidimensional approach, makes clear its dynamic state, predicts adverse outcomes, does not include disease, comorbidity or disability, and meets the criterion of practicability. None of the current conceptual and operational definitions meet these criteria. In this article a new integral conceptual definition of frailty is proposed which meets the criteria of a successful definition. PMID- 20362777 TI - Current trends in feminist nursing research. AB - Despite an increasing number of feminist studies in nursing, few reviews on current trends in feminist nursing research have been published. This article aims to explore the current trends in feminist nursing research and provide recommendations for future feminist studies in nursing. In multiple database searches, 207 articles were retrieved. These were reviewed based on 5 criteria: (1) epistemological background, (2) research questions, (3) research participants, (4) research methods, and (5) implications for changes. The review indicated that feminist nurse researchers with diverse epistemological backgrounds adopted new research methods to ask new questions; expanded their focus to include differences in ethnicity, class, sexual preference, and disability; and incorporated these diversities among women in a global context in their research. Based on these findings, recommendations for future feminist research in nursing are outlined. PMID- 20362778 TI - Toward a national nurse-managed health center data set: findings and lessons learned over 3 years. AB - Although primary care nurse-managed health centers (NMHCs) have gained increasing recognition, there are limited standardized clinical and financial data on these centers. The purpose of this paper is to present the process, benefits, and challenges in collecting standardized national data based on a consensus process from NMHCs over 3 consecutive years. The Institute for Nursing Centers (INC) NMHC Survey focuses on demographic, clinical, and financial data. A detailed codebook accompanied the INC NMHC Survey. A total of 42 NMHCs responded in at least 1 of the 3 years. Despite the challenges in collecting some of the data, especially for the first survey year, data quality improved remarkably when the INC NMHC Survey was repeated. Financial data seemed to be more easily reported than demographic or clinical data. NMHCs increase access to care, often for vulnerable populations, yet to date there are limited standardized clinical and financial data on these centers. The INC NHMC Survey and data described in this paper begins to address that gap. PMID- 20362779 TI - Challenges in tailored intervention research. AB - Although individuals and nurses value tailored health interventions, incorporating tailored interventions into research is fraught with pitfalls. This manuscript provides guidance on addressing challenges on developing, implementing, and evaluating tailored interventions (TIs). The initial step in designing TIs involves selecting the individual characteristics on which to tailor the intervention. After selecting critical characteristics for tailoring, researchers must decide how to assess these characteristics. Then researchers can use manuals, algorithms, or computer programs to tailor an intervention and maintain treatment fidelity. If desired outcomes are not achieved, focus groups or individual interviews may be conducted to gather information to improve the intervention for specific individuals/groups. Then, incorporating study arms of TIs in intervention studies, investigators may compare TIs with standardized interventions statistically and clinically. We believe TIs may have better outcomes, promote better adherence, and be more cost efficient. PMID- 20362782 TI - Preface. PMID- 20362780 TI - Commentary: self and family management frameworks. PMID- 20362783 TI - Outcomes in pancreatic cancer surgery. AB - The increase in surgery for pancreatic cancer during the last 3 decades can be correlated with a gradual decline in operative mortality and postoperative complications. Although not all surgeons (nor all hospitals) can have equal outcomes, the definition and tabulation of these outcomes have been difficult. This article asks several pertinent questions: (1) what is the scientific rationale for pancreatic resection? (2) what are the best available results at this time? (3) who should be performing pancreatic resections? The article analyzes results of resection for adenocarcinoma of the exocrine pancreas, and excludes duodenal and ampullary cancers, pancreatic endocrine tumors, and tumors of less malignant potential. PMID- 20362784 TI - Evidence-based imaging of pancreatic malignancies. AB - A high-quality pancreatic protocol computed tomography (CT) is the primary imaging modality for diagnosing and staging pancreatic malignancy. The main limitation of CT is the lack of sensitivity for early pancreatic lesions. Endoscopic ultrasound (EUS) provides an excellent complement to CT for both diagnosis and staging of pancreatic cancer, and allows easy access for needle aspiration and tissue diagnosis. Magnetic resonance (MR) can be helpful for evaluating small hepatic nodules or cystic lesions of the pancreas, but in general, the role of MR and positron emission tomography remains limited to special situations when the results of CT and EUS are equivocal. PMID- 20362785 TI - The role of endoscopic ultrasonography in the evaluation of pancreatico-biliary cancer. AB - Accurate staging of pancreatico-biliary cancer is essential for surgical planning and for identification of locally advanced and metastatic disease that is incurable by surgery. The complex regional anatomy of the pancreatico-biliary system makes histologic diagnosis of malignancy at this region difficult. The ability to position the endoscopic ultrasound transducer at endoscopy in direct proximity to the pancreas and the bile duct, combined with the use of fine-needle aspiration, enables accurate preoperative staging of cancer, especially cancer too small to be characterized by CT or MRI. Endoscopic ultrasonography (EUS) identifies patients unlikely to be cured by surgery due to vascular invasion or regional nodal metastasis, thereby limiting procedure-related morbidity and mortality. This article focuses on the utility and recent advances of EUS in the evaluation of pancreatico-biliary cancer. PMID- 20362786 TI - The evidence for technical considerations in pancreatic resections for malignancy. AB - The surgeon who wishes to perform successful resections for malignant processes involving the pancreas has to be conversant with a broad range of topics. There are extensive collections of data that usually give excellent guidance, but sometimes also provide conflicting advice. No matter what the data suggest might work best, the surgeon and local collaborators must be able to deliver the quality care cited in some of these reports; usually it is the best results that are published. There is a difference between results that are statistically significant, clinically significant, and important to the patient, and these concepts should never be confused. PMID- 20362787 TI - Solid tumors of the body and tail of the pancreas. AB - Solid lesions of the body and tail of the pancreas challenge all the diagnostic and technical skills of the modern gastrointestinal surgeon. The information available from modern computed tomography (CT), magnetic resonance (MR), and endoscopic ultrasound (EUS) imaging provide diagnostic and anatomic data that give the surgeon precise information with which to plan an operation and to discuss with the patient during the preoperative visit. A preoperative evaluation includes a thorough history and a pancreas protocol CT scan, supplemented by MR imaging and EUS when needed, to differentiate between the various potential diagnoses. These same modalities can be essential in proper staging in the case of malignant lesions, thus aiding in management decisions. Most lesions ultimately require operative resection, barring metastatic disease, with the notable exception of autoimmune pancreatitis. PMID- 20362788 TI - Portal vein resection. AB - The American Hepato-Pancreatico-Biliary Association and Society of Surgical Oncology published a consensus statement in 2009 on the subject of vein resection and reconstruction during pancreaticoduodenectomy (PD), and concluded that PD with vein resection and reconstruction is a viable option for treatment of some pancreatic adenocarcinomas. This article describes the current approaches and recent advances in the management, staging, and surgical techniques regarding portal vein resection. With proper patient selection, a detailed understanding of the anatomy of the root of mesentery, and adequate surgeon experience, vascular resection and reconstruction can be performed safely and does not impact survival duration. Isolated venous involvement is not a contraindication to PD when performed by experienced surgeons at high-volume centers as part of a multidisciplinary and multimodal approach to localized pancreatic cancer. PMID- 20362789 TI - Adjuvant and neoadjuvant therapy in curable pancreatic cancer. AB - Pancreatic cancer is the tenth most common cancer in the United States and the fourth leading cause of cancer death. Afflicting approximately 37,000 Americans yearly, more than 80% of patients are unresectable and, therefore, incurable at the time of their diagnosis. Although surgical resection offers the only opportunity for cure, it remains largely unsuccessful; most patients who are candidates for surgical resection relapse and die in fewer than 5 years. This mortality leaves a 5-year overall survival of about 4% for patients diagnosed with pancreatic cancer. Perhaps the most daunting realization for physicians involved in the management of this disease is the understanding that these numbers have not changed in more than 30 years. As surgery remains the foundation of curative therapy for pancreatic cancer, this article reviews the data on adjuvant chemotherapy and adjuvant chemotherapy with radiotherapy as efforts to boost cure rates. PMID- 20362790 TI - Curative radiation therapy for pancreatic malignancies. AB - Surgery is generally considered as the only curative therapy for pancreatic cancer; however, even with optimal surgery, long-term cure is achieved in very few patients, thus highlighting the need for adjuvant therapies. Radiation therapy, usually in combination with chemotherapy, plays a role in the setting of unresectable, nonmetastatic pancreatic cancer. Its role in the adjuvant setting remains controversial and as yet undefined. This article reviews the role of radiation therapy in the adjuvant and definitive settings, and describes recent improvements in the delivery of radiotherapy that allow for improved dose delivery with decreased toxicity. PMID- 20362791 TI - Palliation in pancreatic cancer. AB - Pancreatic cancer is rarely curable, and because of its location causes significant symptoms for patients in need of palliation. The common problems of incurable pancreatic cancer are biliary obstruction, duodenal obstruction, and pain. Approaches include surgical, endoscopic and radiologic interventions. This article discusses the palliative options and controversies related to these symptoms. PMID- 20362792 TI - Palliative chemotherapy for pancreatic malignancies. AB - Metastatic pancreatic cancer is often one of the most challenging malignancies a medical oncologist faces. Although the primary endpoint of many studies remains overall survival, palliation and quality of life are now more commonly being addressed. The author discusses the most common chemotherapeutic modalities for the treatment of metastatic pancreatic cancer, such as single agent chemotherapy, combination therapy, targeted therapy, and second line treatment. PMID- 20362793 TI - Intraductal papillary mucinous neoplasm: a clinicopathologic review. AB - Intraductal papillary mucinous neoplasm (IPMN) is an intraductal mucin-producing epithelial neoplasm that arises from the main pancreatic duct (MD-IPMN), secondary branch ducts (BD-IPMN), or both (mixed type; Mix-IPMN). Neoplastic progression from benign adenoma to invasive adenocarcinoma has not been proven but is generally thought to occur. With increasing recognition of IPMN, our understanding of the diagnosis and management of the tumors is evolving. At present, treatment options for patients with IPMN range from observation to pancreatic resection depending on the natural history of the lesion. This review focuses on currently available data that guide management decisions for patients with IPMN. PMID- 20362794 TI - Diagnostic evaluation of pancreatic cystic malignancies. AB - Cystic neoplasms of the pancreas are increasingly recognized because of expanding use and improved sensitivity of cross-sectional imaging studies. Major advances in the last decade have led to an improved understanding of the various types of cystic lesions and their biologic behavior. Despite significant improvement in imaging technology and the advent of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) the diagnosis and management of pancreatic cystic lesions remains a significant clinical challenge. Previous "operate in all cases of pancreatic cyst" strategies have been refined and largely replaced using EUS and cyst fluid analysis as the crux for a more practical management approach. The first diagnostic step remains the differentiation between pancreatic pseudocyst and cystic neoplasm. If a pseudocyst has been effectively excluded, the cornerstone issue becomes to determine the malignant potential of the pancreatic cystic neoplasm. In most cases the correct diagnosis and successful management is based not on a single test but on incorporating data from various sources including patient history, radiologic studies, endoscopic evaluation, in particular EUS, and cyst fluid analysis obtained during fine-needle aspirate. This review focuses on describing the various types of cystic neoplasms of the pancreas and their malignant potential, and provide the clinician with a comprehensive diagnostic approach. PMID- 20362796 TI - Laparoscopic management of pancreatic malignancies. AB - Laparoscopic pancreatic resection is performed with increasing frequency for malignant tumors. Data are emerging demonstrating the safety of the laparoscopic approach for distal (left) pancreatectomy, with potential benefits over the standard open approach; however, less information exists as to the effects of laparoscopic resection of cancers of the pancreas. This article reviews and analyzes the existing literature on laparoscopic pancreatectomy for pancreatic malignancies. PMID- 20362795 TI - Pancreatic cystic neoplasms. AB - Cystic neoplasms of the pancreas have been recognized for almost 2 centuries, but the principles of management continue to evolve. Clinicians have a better understanding now of the diverse pathologies and behaviors of cystic neoplasms, and can characterize them more precisely into benign, malignant, and of uncertain potential in their manifestations. Treatment is dependent on accurate diagnosis and tailored to the potential aggressiveness of the lesion, the surgical fitness of the patient, and the probability of effecting long-term palliation or survival of the patient. In this article the authors review the classification based on the World Health Organization classification and the latest evidence-based literature of cystic neoplasms, and present their considerations for surgical management of the various lesions. A better understanding of the biologic potential of cystic neoplasms such as intraductal papillary mucinous neoplasms allows for a more patient-specific evidence-based management plan. PMID- 20362797 TI - US health-care reform: victory, at last. PMID- 20362798 TI - Improving quality of care in the NHS. PMID- 20362799 TI - Education of health professionals for the 21st century: a global independent Commission. PMID- 20362800 TI - Empowering communities for maternal and newborn health. PMID- 20362802 TI - Mind. PMID- 20362803 TI - Samantha Nutt. PMID- 20362804 TI - Sedation versus no sedation in the intensive-care unit. PMID- 20362805 TI - Sedation versus no sedation in the intensive-care unit. PMID- 20362806 TI - Sedation versus no sedation in the intensive-care unit. PMID- 20362807 TI - Everolimus-eluting versus paclitaxel-eluting stents. PMID- 20362810 TI - Everolimus-eluting versus paclitaxel-eluting stents. PMID- 20362811 TI - Complexity: the science for medicine and the human story. PMID- 20362812 TI - Renal Disaster Relief Task Force in Haiti earthquake. PMID- 20362813 TI - Zimbabwe's health sector: the way forward. PMID- 20362814 TI - Monitoring the safety of pandemic H1N1 vaccine. PMID- 20362815 TI - Sudden sensorineural hearing loss. AB - Sudden sensorineural hearing loss is usually unilateral and can be associated with tinnitus and vertigo. In most cases the cause is not identified, although various infective, vascular, and immune causes have been proposed. A careful examination is needed to exclude life threatening or treatable causes such as vascular events and malignant diseases, and patients should be referred urgently for further assessment. About half of patients completely recover, usually in about 2 weeks. Many treatments are used, including corticosteroids, antiviral drugs, and vasoactive and oxygen-based treatments. Although no treatment is proven, we recommend a short course of oral high-dose corticosteroids. There is much to learn about pathogenesis of sudden sensorineural hearing loss, and more clinical trials are needed to establish evidence-based management. PMID- 20362816 TI - Painful palatal swelling. PMID- 20362817 TI - Arthroscopy in China. PMID- 20362819 TI - Glenohumeral chondrolysis article. PMID- 20362820 TI - Quadriceps tendon: the forgotten graft. PMID- 20362822 TI - Biomechanical comparison of transosseous versus suture anchor repair of the subscapularis tendon. AB - PURPOSE: The purpose of this study was to compare the biomechanical properties of transosseous versus suture anchor repair of the subscapularis tendon. We also performed real-time measurement of contact area and pressure of the repair site under rotational loads. METHODS: Six paired human cadaveric shoulders were subjected to rotational loading after repair of the subscapularis tendon. Both shoulders were randomized to transosseous or suture anchor repairs. Real-time pressure sensors were placed between the subscapularis tendon and lesser tuberosity. The repair was subjected to cyclical rotational loading and load-to failure testing. RESULTS: No significant difference was detected in initial pressurized contact area between transosseous repairs (1.70 +/- 0.99 cm(2), 57.88 +/- 30.02% footprint) and suture anchor repairs (1.08 +/- 0.58 cm(2), 34.26% +/- 17.32% footprint). Under cyclical loading, the conditioning elongation of transosseous repairs (0.64 +/- 0.40 mm) was significantly lower (P < .05) than that of suture anchor repairs (2.38 +/- 1.58 mm). No significant difference was found in mean pressurized contact area between the transosseous repairs (2.72 +/- 1.25 cm(2), 94.2% +/- 37.4% footprint) and suture anchor repairs (2.01 +/- 0.89 cm(2), 65.9% +/- 27.9% footprint). For suture anchor repairs, repair-site contact area was significantly (P < .05) smaller than the area of corresponding native insertional footprints; for transosseous repairs, no significant difference was detected. There were no significant differences in peak pressures between the 2 repairs. In the load-to-failure tensile test, there was no significant difference between transosseous repairs (453.2 +/- 66.1 N) and suture anchor repairs (392.6 +/- 78.0 N). CONCLUSIONS: Transosseous and suture anchor repairs of the subscapularis tendon have comparable biomechanical properties. Despite increased conditioning elongation in suture anchor repairs, we found no significant differences in mean contact area between the 2 repairs under cyclical loading. The suture anchor repairs do have a smaller contact area than the native insertional area. Real-time pressure and contact area measurements enabled mapping of the repair site throughout cyclical loading. CLINICAL RELEVANCE: Rotational loading of the subscapularis tendon may provide a more accurate representation of subscapularis tendon injuries. Both techniques showed adequate repair strength; however, neither surgical technique exhibited normal insertional behavior in this time-zero biomechanical study. PMID- 20362823 TI - Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intra-articular pain pump catheter: a report of 18 cases. AB - PURPOSE: To report on our experience of patients who received infusion of bupivacaine with epinephrine after arthroscopic glenoid labral repair surgery and in whom glenohumeral joint chondrolysis subsequently developed, as well as to determine the incidence of such chondrolysis in our surgeons' patient populations. METHODS: A retrospective chart review of 18 patients diagnosed with chondrolysis was carried out. All patients were from 2 experienced orthopaedic surgeons' practices. Details of their clinical course were obtained and summarized. These data were compared with all other arthroscopies completed by the 2 surgeons to determine the incidence of chondrolysis. RESULTS: All 18 patients diagnosed with glenohumeral joint chondrolysis received postoperative infusion of bupivacaine with epinephrine through an intra-articular pain pump catheter (IAPPC). None of the patients received thermal energy as part of their procedure. None of the patients had evidence of glenohumeral joint infection, although an extensive workup was frequently undertaken. Clinically, patients presented with a stiff, painful shoulder. Examination showed decreased range of motion of the affected shoulder. Radiographs and magnetic resonance imaging showed joint space narrowing, as well as subchondral sclerosis and cyst formation. Of the 18 patients, 14 have since undergone repeat arthroscopic procedures, and 5 have received a humeral head-resurfacing operation. Within the same time period, there were 113 arthroscopies, with 45 pain pumps used. Chondrolysis developed in 16 of 32 patients with high-flow IAPPCs and 2 of 12 patients with low-flow IAPPCs (1 patient's IAPPC flow rate was not documented). CONCLUSIONS: Although we cannot establish a causal link, the development of glenohumeral chondrolysis may be related to the intra-articular infusion of bupivacaine with epinephrine postoperatively. We thus caution against the use of IAPPCs. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 20362824 TI - Hamstring strength recovery after hamstring tendon harvest for anterior cruciate ligament reconstruction: a comparison between graft types. AB - PURPOSE: The purpose of this study was to investigate hamstring strength after harvest of 1 or 2 hamstring tendons for anterior cruciate ligament reconstruction. METHODS: We recruited 50 individuals who had returned to regular sporting activity to participate in a comparative study at a mean of 32.5 months after anterior cruciate ligament reconstructive surgery (30 in semitendinosus gracilis group and 20 in semitendinosus group). Isokinetic hamstring strength (at 60 degrees/s and 180 degrees/s with the peak torque and torque produced at 60 degrees, 90 degrees, and 105 degrees of knee flexion recorded) and isometric hamstring strength (at 30 degrees, 90 degrees, and 105 degrees of knee flexion) were measured, and the standing knee flexion angle was used to evaluate functional hamstring strength recovery. RESULTS: No significant differences between the groups were found in any of the isometric or isokinetic strength measures or in the standing knee flexion angle. No relation was found between the standing knee flexion angle and the isometric hamstring strength results obtained at 105 degrees of knee flexion (r(2) = 0.034). CONCLUSIONS: These findings show that the choice of hamstring tendon graft-that is, semitendinosus alone or semitendinosus and gracilis-is unlikely to significantly influence postoperative hamstring strength outcomes in athletes returning to sports postoperatively. Both graft choices showed strength deficits of between 3% and 27% compared with the nonoperated limb, indicating that hamstring strength deficits persist despite successful completion of rehabilitation. The results also show that the standing knee flexion angle should not be used as a surrogate clinical measure of hamstring strength. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 20362825 TI - Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. AB - PURPOSE: To investigate whether the application of a particular platelet-rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. METHODS: This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF-assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second-look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second-look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL-like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. RESULTS: The overall arthroscopic evaluation of PRGF-treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups (P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls (P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF-treated grafts and 40% of controls. The appearance of the connective tissue envelope changed with increasing time from surgery. On the basis of the histologic findings, we suggest that the remodeling of PRGF-treated grafts involves the formation of synovial like tissue enveloping the graft. This tissue is eventually integrated in the remodeled tendon graft, conferring a similar appearance to the normal ACL. CONCLUSIONS: The use of PRGF influenced the histologic characteristics of tendon grafts, resulting in more remodeling compared with untreated grafts. We have shown temporal histologic changes during the 6- to 24-month postoperative period of graft maturation, with newly formed connective tissue enveloping most grafts treated with PRGF. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 20362826 TI - The relation between tunnel widening and bone mineral density after anterior cruciate ligament reconstruction: an experimental study in sheep. AB - PURPOSE: The aim of this study was to analyze the relation between bone mineral density (BMD) and femoral tunnel enlargement (TE) in a previously validated sheep model of soft-tissue anterior cruciate ligament (ACL) reconstruction. METHODS: Thirty sheep underwent ACL reconstruction by use of a soft-tissue graft at the age of 4 months. Graft fixation was achieved with the EndoButton (Smith & Nephew Endoscopy, Andover, MA) and Suture Washer (Smith & Nephew Endoscopy). Six animals were killed at 0, 3, 6, 12, and 24 weeks postoperatively. Each ACL-reconstructed knee was examined both by computed tomography to analyze the bone tunnel cross sectional area and by dual-energy x-ray absorptiometry to analyze BMD. RESULTS: There was a significant increase in tunnel cross-sectional area. BMD decreased significantly within the first 3 weeks after surgery and increased thereafter. A positive correlation between TE and BMD was found. However, a subgroup analysis showed that there is no influence of BMD on the development of a tunnel widening. CONCLUSIONS: The hypothesis that a TE would be associated with a loss in BMD was not confirmed. Tunnel widening during the first 6 months after ACL reconstruction is not affected by the transient changes in BMD. CLINICAL RELEVANCE: There is no correlation between TE and BMD in an experimental sheep model of ACL reconstruction. Translational investigations will determine whether this is also true in humans. PMID- 20362827 TI - Anterior cruciate ligament reconstruction using patellar tendon allograft: an age dependent outcome evaluation. AB - PURPOSE: To compare the outcomes of a consecutive series of nonrevision bone patellar tendon-bone (BPTB) allograft anterior cruciate ligament (ACL) reconstructions in patients aged 40 years or older and patients aged younger than 40 years. METHODS: Prospectively collected data from consecutive BPTB allograft ACL reconstructions fixed with biodegradable interference screws and performed by a single surgeon were analyzed by use of established outcome measures. Preoperative and postoperative outcome assessments included Cincinnati, Lysholm, and Tegner scores and International Knee Documentation Committee (IKDC) activity scores. Lachman test, pivot-shift test, and KT arthrometer (MEDmetric, San Diego, CA) measurements were obtained at a minimum of 24 months after surgery. RESULTS: In total, 32 patients met the inclusion criteria (21 men and 11 women). The mean follow-up was 35 months (range, 24 to 58 months). Of the patients, 21 were aged younger than 40 years (66%) and 11 were aged 40 years or older (34%). The mean age was 35 years (range, 18 to 55 years). In patients aged younger than 40 years, the mean postoperative Cincinnati score was 82.4 (39.1 preoperatively); Tegner score, 6.2 (3.9 preoperatively); Lysholm score, 89.5 (46.8 preoperatively); and IKDC activity score, 2.7 out of 4 (1.7 preoperatively). Five patients had a positive postoperative Lachman test, but none had a positive pivot-shift test. KT examinations showed a manual maximum difference of less than 3 mm in all but 1 patient (mean, 0.7 mm). In patients aged 40 years or older, the mean postoperative Cincinnati score was 83.8 (44.4 preoperatively); Tegner score, 6.6 (3.9 preoperatively); Lysholm score, 88.8 (50.1 preoperatively); and IKDC activity score, 2.7 out of 4 (2.1 preoperatively). One patient had a positive postoperative Lachman test, but none had a positive pivot-shift test. KT examinations showed a manual maximum difference of less than 3 mm in all but 1 patient (mean, 1.3 mm). CONCLUSIONS: The outcomes of BPTB allograft ACL reconstructions were not different both subjectively and objectively for patients aged 40 years or older and patients aged younger than 40 years. BPTB allograft ACL reconstruction provides consistent results for patients of all age groups. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 20362828 TI - Diagnostic ultrasound evaluation of posterolateral corner knee injuries. AB - PURPOSE: The purpose of this study was to determine whether dynamic ultrasound (US) would be able to differentiate posterolateral corner knee injuries that would require surgical intervention. METHODS: This is a single-group cohort study. A knee sonogram was obtained in patients referred to us with suspected posterolateral knee injury. In addition to static US imaging, a dynamic US stress test was performed by placement of maximum varus stress on the knee at 30 degrees of flexion. The tibiofemoral separation was then measured with US. Results from US and surgery were then compared. RESULTS: Sixteen patients had US and underwent surgery, and twelve patients had surgical findings requiring surgical intervention to the posterolateral knee structures. With regard to static US images, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 92%, 75%, 92%, 75%, and 88%, respectively, for the lateral collateral ligament; 33%, 100%, 100%, 33%, and 50%, respectively, for the popliteus; and 67%, 75%, 67%, 75%, and 69%, respectively, for the popliteofibular ligament. The dynamic US stress test showing 10.5 mm of lateral joint space width or more during varus stress showed a sensitivity of 83% and specificity of 100% for injury to the lateral collateral ligament and posterolateral corner structures, with a positive predictive value of 100%, negative predictive value of 75%, and accuracy of 88%. CONCLUSIONS: A positive dynamic US stress test (>or=10.5 mm) positively predicted the need for posterolateral knee surgery in 100% of patients in this study who required posterolateral corner repair or reconstruction. LEVEL OF EVIDENCE: Level I, testing of previously developed diagnostic criteria in series of consecutive patients with universally applied gold standard. PMID- 20362829 TI - Anterior cruciate ligament tibial guide pin accuracy and surgical precision: comparing 3.0-mm and 2.4-mm guide pins. AB - PURPOSE: The purpose of this study was to evaluate the accuracy of a 3.0-mm diameter anterior cruciate ligament (ACL) tibial guide pin versus a standard, 2.4 mm drill-tipped guide pin. A secondary purpose was to evaluate surgeon precision in identifying the true (anatomic) center of the ACL tibial footprint using arthroscopic visualization. METHODS: Five matched pairs of cadaveric knees were disarticulated, leaving a well-defined footprint of the ACL on the tibial plateau. The tibial footprint was digitally recorded by a bioengineer, and the true center of the footprint was calculated. Next, using arthroscopic visualization, a surgeon identified and marked his estimation of the true center of the ACL tibial footprint. This mark was then digitally recorded by the bioengineer and compared with the calculated center, allowing quantification of surgeon anatomic precision. Finally, under arthroscopic visualization, the surgeon was given 1 attempt to aim and drill the guide pin to his mark. Pin position was digitally recorded; the distance of the drill pin from the mark quantifies drill pin placement accuracy. RESULTS: Mean accuracy for the 3.0-mm guide pin was 2.87 +/- 1.19 mm versus 6.98 +/- 1.29 mm for the 2.4-mm pin. The difference was significant (P = .005). Surgeon anatomic precision was 3.32 +/- 2.10 mm. CONCLUSIONS: Our results show that a 3-mm ACL tibial guide pin is significantly more accurate than a 2.4-mm-diameter pin. The 3-mm pin accuracy is within the range of surgeon precision; the 2.4-mm pin accuracy is not. CLINICAL RELEVANCE: Pin accuracy and surgeon precision are clinically relevant measures because anatomic tunnel placement is a determinant of ACL reconstruction outcome. PMID- 20362830 TI - Sports and sports medicine in China in the post-Olympics era. PMID- 20362831 TI - Single-bundle posterior cruciate ligament reconstruction and mini-open popliteofibular ligament reconstruction in knees with severe posterior and posterolateral rotation instability: clinical results of minimum 2-year follow up. AB - PURPOSE: The aim of this study was to assess the clinical outcome of arthroscopy assisted posterior cruciate ligament (PCL) reconstruction and mini-open popliteofibular ligament (PFL) reconstruction for severe posterior and posterolateral rotation instability of the knee with lateral collateral ligament intact. METHODS: Arthroscopic PCL reconstruction and mini-open PFL reconstruction were performed consecutively in 24 patients with chronic posterior and posterolateral rotation instability of the knee. The inclusion criteria for surgery were a side-to-side difference in posterior translation of more than 12 mm measured with stress radiography and tibial external rotation of 10 degrees more than that of the contralateral uninjured knee without varus laxity. The exclusion criterion was combined anterior cruciate ligament injury. The patients underwent single-bundle PCL reconstruction with Achilles tendon allograft. A mini open PFL reconstruction was performed with anterior tibialis allograft. A 2-cm incision was made on the lateral epicondyle to build the femoral tunnel, and a 3 cm incision was made near the fibular head for the fibular tunnel. RESULTS: The minimum follow up was 2 years. At final follow up, 18 patients (75% [18 of 24]) were enrolled in the study group and 6 patients were lost. Postoperatively, mean posterior tibial translation (side-to-side difference) in our patients was reduced from 17.3 +/- 4.1 mm to 4.6 +/- 3.2 mm. Tibial external rotation was decreased from a mean of 14.7 degrees +/- 4.6 degrees to -2.8 degrees +/- 3.8 degrees, as compared with the contralateral uninjured knee. These differences were statistically significant. The International Knee Documentation Committee grade preoperatively was grade D in all 18 patients, whereas postoperatively, 5 were classified as grade A, 8 as grade B, and 5 as grade C. CONCLUSIONS: In this small clinical series, single-bundle PCL reconstruction combined with mini-open PFL reconstruction was proven to correct pathologic excessive posterior and posterolateral rotation instability. LEVEL OF EVIDENCE: Level IV, therapeutic case series (no control or historical group). PMID- 20362832 TI - Anterior cruciate ligament reconstruction with LARS artificial ligament: a multicenter study with 3- to 5-year follow-up. AB - PURPOSE: The aim of this multicenter study was to evaluate the clinical outcome of anterior cruciate ligament (ACL) reconstruction by use of the Ligament Advanced Reinforcement System (LARS) artificial ligament (Surgical Implants and Devices, Arc-sur-Tille, France) with 3- to 5-year follow-up. METHODS: From August 2004 to July 2006, 159 patients with ACL rupture underwent arthroscopic ACL reconstruction with LARS artificial ligament at 4 orthopaedic sports medicine centers in China. They were retrospectively followed up for 50 +/- 6 months (range, 36 to 62 months). Outcome assessment included physical examination, KT 1000 arthrometer testing (MEDmetric, San Diego, CA), magnetic resonance imaging, radiography, Lysholm score, Tegner score, International Knee Documentation Committee score, and subjective satisfaction rate. Quadriceps and hamstring isokinetic strength was evaluated in 68 patients. RESULTS: The side-to-side difference in anterior translation (injured side - uninjured side) measured by KT 1000 arthrometer was 1.5 +/- 1.6 mm (range, -1 to 7 mm) postoperatively, and knee stability was significantly improved compared with preoperative data (P < .0001). Quadriceps and hamstring isokinetic peak torque of the injured limb expressed as a percentage of the contralateral limb was 93.6 +/- 10.7 and 95.8 +/- 12.0, respectively. The Lysholm score improved from 65.1 +/- 12.3 points (range, 30 to 95 points) preoperatively to 94.5 +/- 7.0 points (range, 65 to 100 points) postoperatively (P < .0001). The Tegner score improved from 3.1 +/- 1.6 (range, 0 to 6) preoperatively to 6.1 +/- 1.5 (range, 1 to 9) postoperatively (P < .0001). According to the International Knee Documentation Committee score, 94% of patients were graded A or B at last follow-up. Ninety-three percent of patients were very satisfied or satisfied with their outcome. LARS artificial ligament rupture occurred in 3 patients; knee synovitis developed in 1 of these patients. CONCLUSIONS: ACL reconstruction with LARS artificial ligament used in patients with the ACL stump preserved in the acute and chronic phases has a very good outcome at mean of 50 months' follow-up. The overall complication rate for ACL reconstruction with LARS artificial ligament is 5.7%, and knee synovitis developed in only 1 case. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 20362833 TI - Combination of modified Brostrom procedure with ankle arthroscopy for chronic ankle instability accompanied by intra-articular symptoms. AB - PURPOSE: To evaluate the effectiveness of the modified Brostrom procedure combined with ankle arthroscopy for chronic ankle instability (CAI) accompanied by intra-articular symptoms. METHODS: We identified 85 consecutive patients with CAI (87 ankles). There were 58 male patients (58 ankles) and 27 female patients (29 ankles) with a mean age of 24.4 years (range, 14 to 36 years). All the patients had intra-articular symptoms. Ankle arthroscopic surgery was performed initially to manage any intra-articular lesions. This was followed by the modified Brostrom procedure, including shortening of the anterior talofibular ligament and/or calcaneofibular ligament, as well as extensor retinaculum augmentation. All the intra-articular lesions found during surgery were recorded. American Orthopaedic Foot & Ankle Society (AOFAS) scores were obtained before surgery and at follow-up. RESULTS: Intra-articular lesions were found in 79 ankles (90.8%), including 75 with synovitis and soft-tissue impingement, 33 with chondral injuries, 23 with anterior tibial osteophytes, 7 with loose bodies, and 6 with distal tibiofibular syndesmosis injuries. A total of 79 patients (92.9%) (81 ankles) were followed up for a mean of 29 months (range, 12 to 47 months). The mean AOFAS score improved from 46.6 +/- 8.1 preoperatively to 86.5 +/- 7.6 postoperatively (P < .05). Mean postoperative AOFAS scores were significantly higher in patients without chondral lesions than in those with chondral lesions (89.76 +/- 5.88 and 81.35 +/- 7.18, respectively; P < .05). Improvements in AOFAS scores after surgery were significantly greater in patients without chondral lesions than in those with chondral lesions (42.28 +/- 9.04 and 36.06 +/- 11.85, respectively; P < .05). CONCLUSIONS: The modified Brostrom procedure combined with ankle arthroscopy produced satisfactory surgical outcomes in patients with CAI and intra-articular symptoms. Accompanying chondral injuries were associated with poorer surgical outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 20362834 TI - Is the extended release of the inferior glenohumeral ligament necessary for frozen shoulder? AB - PURPOSE: The aims of our study were to assess effects of the extent of capsular release and to define the benefit of additional release of the inferior glenohumeral ligament (IGHL) from inferior to posterior in frozen shoulder. METHODS: Seventy-four consecutive patients with refractory frozen shoulder underwent arthroscopic capsular release and were divided into 2 groups randomly. The release of anterior capsular structures, including the anterior band of the IGHL, was performed in group 1. In group 2 the release extended inferiorly and posteriorly. Constant functional scores were used to assess the outcome. The range of motion (ROM) in various directions was also recorded preoperatively and postoperatively. RESULTS: Follow-up was obtained in 41 patients in group 1 and 29 patients in group 2, and it averaged 28 months. At the last follow-up, there was a significant improvement in Constant score (P < .01) postoperatively in all patients. There was a significant and rapid reduction in the visual analog scale score in both groups postoperatively. No statistical difference in the visual analog scale score was found between the 2 groups at the corresponding time points. Overall, patients had restored shoulder ROM at the last follow-up without difference between group 1 and group 2. Abduction, flexion, external rotation at 90 degrees of abduction, internal rotation at 0 degrees of abduction, and internal rotation at 90 degrees of abduction recovered more rapidly in group 2 within 3 months after surgery; however, there was no significant difference in ROM after 6 months. CONCLUSIONS: In this broad group of patients with recalcitrant adhesive capsulitis, the addition of the posterior capsular release did not improve patient function or ROM over anterior capsular release alone at 6 months. The extended release of the inferior and posterior IGHL would improve ROM more rapidly within the first 3 months postoperatively. LEVEL OF EVIDENCE: Level I, therapeutic randomized controlled trial. PMID- 20362835 TI - Arthroscopy classics. Hip arthroscopy by the lateral approach. PMID- 20362836 TI - The outcome of type II SLAP repair: a systematic review. AB - PURPOSE: The purpose of this study was to systematically review the literature regarding the outcome of arthroscopic repair of type II SLAP lesions in order to assess the effectiveness of current methods of treatment. METHODS: We performed a systematic review of the results of repair of type II SLAP lesions. Inclusion criteria included outcome studies of repair of type II SLAP lesions with minimum 2-year follow-up and Level IV evidence or higher published in the English language in peer-reviewed journals. RESULTS: There is no Level I or II evidence for SLAP repair outcome. Regarding the general outcome after type II SLAP repair, the percentage of good and excellent results ranged from 40% to 94%. Return to previous level of play ranged from 20% to 94%. Overhead athletes are the most challenging to return to the previous level of performance for this diagnosis, and their return rate reflects this. Five studies reported these results, and the rate of return ranged from 22% to 64% for baseball players. CONCLUSIONS: Arthroscopic repair of type II SLAP tears results in overall excellent results for individuals not involved in throwing or overhead sports. The results of type II SLAP repair in throwing or overhead athletes are much less predictable. Future studies should be prospective in nature and at least use a longitudinal prospective cohort design to determine predictors of outcome. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies. PMID- 20362837 TI - Computer-assisted anterior cruciate ligament reconstruction: an evidence-based approach of the first 15 years. AB - In the last 15 years, computer-assisted surgery (CAS) has been used for many purposes during anterior cruciate ligament (ACL) reconstruction, such as tunnel positioning, joint laxity evaluation, and biomechanical studies. This article is an evidence-based literature review of the contribution of such technology to ACL surgery. A search of the PubMed and Medline databases was performed. Articles were classified according to the study design and to the research topic: anatomy, laxity, kinematics, and comparison of surgical techniques. An evidence-based approach was used to verify the clinical usefulness of CAS to ACL surgery. The use of CAS for research purposes was also evaluated. CAS was shown to improve femoral tunnel positioning, even if clinical outcomes showed no differences compared with manual techniques. CAS technology was found to be useful for research purposes in terms of providing a better comprehension of the effect of different ACL reconstructions and of the different bundles on joint laxity, as well as describing tunnel positioning in relation to native ACL insertion. CAS in ACL surgery can improve results at time 0 and can improve knowledge about ACL anatomy and kinematics. Its application remains limited mostly to research purposes because of the invasiveness of the system and the absence of improved clinical results at follow-up. PMID- 20362838 TI - Four-quadrant approach to capsulolabral repair: an arthroscopic road map to the glenoid. AB - Advancing technology, improved instrumentation, and a desire to address intra articular pathology with a minimally invasive approach have driven the expansion of arthroscopic shoulder surgery in the past 2 decades. Proponents cite greatly improved visualization, lack of the need to perform a capsulotomy, fewer subscapularis issues postoperatively, and improved access to the entire glenohumeral joint. Our understanding and recognition of glenohumeral joint pathology have improved, and our ability to appropriately treat it has also improved. Aside from the anteroinferior and superior capsulolabral injury, orthopaedic surgeons have encountered and are able to address combined lesions, posterior labral tears, 270 degrees to 360 degrees labral tears, capsular laxity, humeral avulsion of the glenohumeral ligaments, associated glenoid or humeral bone loss, and partial-thickness rotator cuff tears. To adequately address the extent of pathology encountered in a shoulder instability case, access to the inferior, posteroinferior, and posterior aspects is necessary. In this technical article we present a simplified approach using safe access points by dividing the glenohumeral joint into 4 quadrants that allows for ease of instrumentation and implant placement. This will provide a blueprint for the treatment of capsulolabral injuries. In addition to portal selection and location, we will discuss several instruments we believe are advantageous in tissue manipulation and suture management. PMID- 20362839 TI - Arthroscopic posterior cruciate ligament reconstruction in a skeletally immature patient: a new technique with case report. AB - Pediatric intrasubstance posterior cruciate ligament (PCL) injuries are rare but present a significant treatment challenge. Untreated instability may lead to further knee injury, including meniscal or chondral damage. Surgical intervention risks damage to the physis, growth arrest, and angular deformity. We present the case of a skeletally immature 11-year-old boy with a high-grade intrasubstance PCL injury reconstructed using an all-arthroscopic tibial inlay technique modified to minimize risk of physeal injury. The femoral tunnels were placed entirely within the epiphysis, and the tibial physis was minimally crossed with a small drill hole and suture material. At 17 months' follow up, the patient had returned to full activity, including sports. He had a grade 1 posterior drawer and no posterior sag. Radiographs showed no degenerative changes. Both the proximal tibial and distal femoral physes were widely patent with no angular deformity. The patient had a 1-cm leg length discrepancy, with the operative limb being longer. This technical note with a case report describes a novel physeal sparing reconstruction of the PCL in a pediatric patient with open physes. PMID- 20362840 TI - Accommodating IOL: is the name already justified? PMID- 20362841 TI - Lift and crack technique for risky cataract cases. AB - We describe a technique to manage dense cataract cases. After a capsulorhexis of 6.0 to 7.0 mm diameter has been created, the phaco tip is inserted into the nucleus centrally and high vacuum is used to lift the nucleus and elevate it with a tilt to protrude outside the capsular bag distally. The chopper is used to segment the nucleus centripetally, starting from the lens equator or just behind, without applying stress to the capsular bag or zonules. Further phacoemulsification is maintained by holding the nucleus centrally and chopping it into smaller triangular sectoral pieces. In this horizontal chopping technique, which is done just outside the capsular bag, grasping the nucleus in the center and elevating it with high vacuum instead of depressing one edge of the nucleus to elevate the other edge prevents additional stress to the capsule and zonules. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned. PMID- 20362842 TI - Use of low-cost video recording device in reflective practice in cataract surgery. AB - Reflective surgical practice is invaluable for surgeons at all levels of experience. For trainees in particular, every surgical opportunity must be optimized for its learning potential. Recording and reviewing cataract surgery is an invaluable tool. We describe a video recording device that has the advantages of ease of use; low cost; portability; and ease of review, editing, and dissemination, all of which encourage regular use and reflective surgical practice. PMID- 20362843 TI - Contrast sensitivity measurement with 2 contrast sensitivity tests in normal eyes and eyes with cataract. AB - PURPOSE: To assess the reliability of and correlation between 2 contrast sensitivity tests in normal eyes and eyes with cataract. SETTING: Department of Ophthalmology, Yonsei University Hospital, Seoul, Korea. METHODS: The Vision Contrast Test System (wall-chart test) and Optec 6500 system (view-in test) were used to measure contrast sensitivity in normal eyes at 2 visits separated by 2 weeks and in eyes with cataract before and 2 months after cataract surgery. The test-retest reliability and correlation were calculated by the intraclass correlation coefficient (ICC), coefficient of repeatability (COR), and 95% range of difference using the Bland-Altman method. RESULTS: The study evaluated 40 normal eyes of 20 subjects and 44 eyes of 38 cataract patients. The repeatability of the 2 test methods was generally acceptable. The view-in test performed better than the wall-chart test in the ICC analysis (0.85 versus 0.65) but not in the COR analysis (+/-0.20 log versus +/-0.27 log). Correlation between the 2 tests was poor in both groups of eyes. The ceiling effect was greater with the wall chart test. The floor effect occurred mainly in patients with cataract, in which it was greater preoperatively than postoperatively; at high frequency; and with the view-in test. CONCLUSION: Based on the ceiling and floor effect, the view-in test is better for detecting subtle contrast sensitivity changes in normal or near-normal eyes and the wall-chart test is useful in eyes with compromised vision. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 20362844 TI - Autorefraction after implantation of diffractive multifocal intraocular lenses. AB - PURPOSE: To evaluate whether autorefractometry values after implantation of diffractive multifocal intraocular lenses (IOLs) correlate with manifest refraction values. SETTING: Tokyo Dental College Suidobashi Hospital, Tokyo, Japan. METHODS: This retrospective study evaluated eyes that had cataract surgery with implantation of a diffractive multifocal IOL. One month or more postoperatively, the autorefraction values were compared with the manifest refraction values to determine the correlation between the 2 methods in sphere, cylinder, and spherical equivalent (SE). RESULTS: The study evaluated 156 eyes of 84 patients. The mean spherical refraction was 0.13 diopters (D) +/- 0.66 by autorefraction and 0.26 +/- 0.50 D by manifest refraction. The mean cylinder value was 0.94 +/- 0.58 D and 0.61 +/- 0.48 D, respectively. The mean SE was 0.34 +/- 0.66 D and -0.06 +/- 0.48 D, respectively. All 3 measurements by autorefraction and manifest refraction were well correlated (r(2) = 0.67, 0.66, 0.64, respectively). CONCLUSION: Findings show that postoperative autorefraction can be used to estimate the manifest refraction in eyes with diffractive multifocal IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 20362845 TI - Correlation between optics quality of multifocal intraocular lenses and visual acuity: tolerance to modulation transfer function decay. AB - PURPOSE: To study the relationship between the optics quality of multifocal intraocular lenses (IOLs) and distance-corrected near, intermediate, and distance visual acuity to determine the degree to which optics quality must change to produce a significant difference in visual acuity. SETTING: Fundacion Oftalmologica del Mediterraneo, Valencia, Spain. METHODS: Monocular distance corrected visual acuity (decimal and logMAR) was measured at 4 m, 70 cm, and 30 cm under photopic and mesopic conditions in eyes with 1 of 3 multifocal IOL models. Visual acuity versus the "average modulation" of the IOL was assessed. RESULTS: The pupil diameter and patient age were similar between the 3 IOL groups (20 eyes each). A difference in average modulation (ie, optics quality) up to 15% did not produce significant differences in mean visual acuity between 2 groups; however, there was a significant difference in mean visual acuity between 2 groups when the average modulation values differed by at least 25%. The slope of the linear correlation between visual acuity and average modulation was 0.018 (r(2) = 0.91) under photopic conditions and 0.024 (r(2) = 0.089) under mesopic conditions. CONCLUSIONS: There was a strong linear correlation between IOL optics quality and visual acuity with distance correction under photopic conditions with a pupil of approximately 3.5 mm in a cohort in which the patient age was controlled. The correlation was similar under mesopic conditions. The eye's tolerance to modulation transfer function decay was approximately 15% of the average modulation value. PMID- 20362846 TI - Pupil dilation using a standard cataract surgery regimen alone or with atropine 1.0% pretreatment: prospective comparative evaluation. AB - PURPOSE: To compare the amount of pupil dilation produced by a set of commonly used preoperative mydriatic agents for cataract surgery, with the same regimen preceded by topical administration of atropine 1.0%. SETTING: Department of Ophthalmology, Loma Linda University, Loma Linda, California, USA. METHODS: In this prospective unmasked study, the baseline pupil size in eyes of volunteers was measured. Pupil size was then measured 30 minutes after instillation of the institution's standard dilation regimen for cataract surgery, which included phenylephrine 2.5%, tropicamide 1.0%, and cyclopentolate 1.0%. Several days later, the subjects returned for repeat measurements after pretreating the study eye(s) with atropine 1.0% 3 times a day the day previously and once on the morning of repeat dilation and measurements. Pupil size was again measured after administration of the standard regimen. RESULTS: The study included 72 eyes of 54 patients. A paired t test showed a statistically significant difference in mean pupil dilation between the standard regimen alone and the standard regimen with atropine 1.0% pretreatment. The mean pupil dilation was 7.3 mm +/- 1.2 (SD) with the standard regimen alone and 6.9 +/- 1.2 mm with the standard regimen with atropine pretreatment; the difference was statistically significant (P<.001). CONCLUSION: The addition of atropine 1.0% 1 day before administration of a standard preoperative dilating regimen for cataract surgery resulted in a smaller dilated pupil diameter than administration of the standard set of preoperative mydriatic agents alone. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 20362847 TI - Collagen copolymer toric posterior chamber phakic intraocular lens for myopic astigmatism: one-year follow-up. AB - PURPOSE: To assess the predictability, efficacy, safety, and stability of collagen copolymer toric phakic intraocular lens (pIOL) implantation to correct moderate to high myopic astigmatism. SETTING: Fernandez-Vega Ophthalmological Institute, Oviedo, Spain. METHODS: This study comprised eyes that had implantation of a toric Intraocular Collamer Lens for moderate to high myopic astigmatism. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, pIOL vault, and adverse events were evaluated over 12 months. RESULTS: Preoperatively, the mean sphere in the 55 eyes was -4.65 diopters (D) +/- 3.02 (SD) (range -0.50 to -12.50 D) and the mean cylinder, -3.03 +/- 0.79 D (range -1.25 to -4.00 D). At 12 months, the mean Snellen decimal UDVA was 0.80 +/- 0.20 and the mean CDVA, 0.85 +/- 0.18; 62.0% of eyes had a CDVA of 20/20. More than 50.0% of eyes gained 1 or more lines of CDVA. The treatment was highly predictable for spherical equivalent (SE) (r(2) = 0.99) and astigmatic components J0 (r(2) = 0.97) and J45 (r(2) = 0.99). Of the eyes, 94.5% were within +/-0.50 D of the attempted SE and all were within +/-1.00 D. For J0, 94.5% of eyes were within +/-0.50 D and for J45, 98.2% of eyes; all eyes were within +/ 1.00 D. The efficacy index was 0.95 at 3 months and 1.08 at 1 year. CONCLUSIONS: The UDVA and CDVA with toric pIOLs were good and highly stable over 12 months, confirming the procedure is safe, predictable, and effective for correction of moderate to high astigmatic. PMID- 20362848 TI - Outcomes of reenclavation of subluxated iris-fixated phakic intraocular lenses: comparison with primary surgery outcomes. AB - PURPOSE: To study the outcomes of successful reenclavation of subluxated iris fixated phakic intraocular lenses (pIOLs). SETTING: Tertiary eyecare referral center. METHODS: Interventional case series comprised eyes with a subluxated Verisyse pIOL that had successful reenclavation of 1 haptic. A comparison of outcomes between primary pIOL implantation surgery and subsequent reenclavation was performed. The parameters were uncorrected (UDVA) and corrected (CDVA) distance visual acuity and the quantitative endothelial changes preoperatively and postoperatively at 1 week and 1, 3, and 6 months. RESULTS: Nine eyes of 6 patients were evaluated. Disenclavation was spontaneous in 6 eyes (66.6%) and posttraumatic in 3 eyes (33.3%). The mean UDVA and CDVA at 6 months were comparable between primary surgery and reenclavation. The subluxation and subsequent reenclavation did not cause statistically significant endothelial cell loss; endothelial cell loss after reenclavation was comparable to that after primary surgery (P = .953). CONCLUSION: Successful subluxation of iris-fixated pIOLs did not cause significant damage to the ocular structures or lead to serious complications. PMID- 20362849 TI - Trypan blue staining for capsulorhexis: ultrastructural effect on lens epithelial cells and capsules. AB - PURPOSE: To evaluate the ultrastructural effect of trypan blue 0.1% staining for capsulorhexis on lens epithelial cells (LECs) and capsules. SETTING: Division of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. METHODS: Before capsulorhexis, patients were randomly assigned to 1 of 2 groups. Trypan blue 0.1% staining was performed in the treatment group. No trypan blue was used in the control group. Samples of capsules with LECs were fixed and analyzed with routine optical microscopy techniques, immunohistochemistry for beclin-1 expression (a marker of autophagy), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling to detect apoptosis, and transmission electron microscopy (TEM). Morphometric analyses were performed, and the 2 sets of data were compared. RESULTS: Each group comprised 15 patients. Cell death by autophagy and apoptosis was observed in the treatment group but not in the control group. The TEM images of subcapsular epithelium cells showed mitochondrial rupture, dilation of the cisterns of the endoplasmic reticulum, increased cytoplasmic and nuclear electron density, and abnormalities in the nuclear profile of trypan blue-stained cells. Morphometric analysis showed statistically significant differences between the 2 groups in the longest nuclear axes and the ratio between the total nuclear perimeter and the cell area (P = .03). The difference in capsule thickness between groups was not significant. CONCLUSION: Trypan blue caused LEC death, which supports the hypothesis that staining with trypan blue 0.1% can help reduce the incidence of posterior capsule opacification after cataract surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 20362850 TI - Impact of high and low aspiration parameters on postoperative outcomes of phacoemulsification: randomized clinical trial. AB - PURPOSE: To compare the effects of fluidic parameters on the central corneal thickness (CCT), corneal endothelium, and anterior segment inflammation after phacoemulsification with longitudinal ultrasound. SETTING: Iladevi Cataract & IOL Research Center, Ahmedabad, India. METHODS: In this prospective randomized patient- and examiner-masked study, consecutive patients with age-related cataract were randomly assigned to Group 1 (low fluidic parameters: aspiration flow rate 25 cc/min; bottle height 70 cm and 90 cm; vacuum .05, Wilcoxon test). The mean difference between the 2 tonometers after LASIK was 0.1 +/- 2.1 mm Hg. The 95% limits of agreement ranged from -4.26 to 4.05 mm Hg. The IOP reduction with rebound tonometry was positively correlated with preoperative IOP. CONCLUSION: There was a greater decrease in IOP measurement after LASIK by rebound tonometry, showing this method was more affected by surgery. PMID- 20362857 TI - Conventional versus custom ablation in photorefractive keratectomy: randomized clinical trial. AB - PURPOSE: To compare visual outcomes and changes in total higher-order aberrations (HOAs) between conventional photorefractive keratectomy (PRK) and custom PRK SETTING: Department of Ophthalmology, Labbafinejad Medical Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences and Negah Eye Center, Tehran, Iran. METHODS: This clinical trial comprised eyes having bilateral myopic PRK with the Technolas 217z excimer machine. One eye had conventional ablation (conventional group) and the other eye, wavefront-guided custom treatment (custom group). Changes in postoperative visual acuity, cycloplegic refraction, contrast sensitivity function, and root mean square higher-order aberrations (RMS HOAs) were compared between the 2 groups. RESULTS: The mean age of the 28 patients (56 eyes) was 26.7 years. The mean preoperative cycloplegic spherical equivalent refractive error was -4.92 diopters (D) +/- 1.6 (SD) and the mean refractive astigmatism, 0.91 +/- 1.0 D. There was no statistically significant difference between the 2 groups in preoperative cycloplegic refractive error, HOAs, or contrast sensitivity function. The mean follow-up was 8.1 +/- 3.3 months. The increase in RMS HOAs from preoperatively to postoperatively was statistically significantly higher in the custom group in the 6.0 mm zone (P = .03) but not in the 4.0 mm zone (P = .26). The decrease in low mesopic contrast sensitivity function was statistically significant in both groups. CONCLUSIONS: The RMS HOAs significantly increased after PRK with both methods. The results suggest that custom ablation is more sensitive to optical zone (OZ) size and may yield more aberrations with an OZ smaller than 6.0 mm. PMID- 20362858 TI - Comparison of 2 laser instruments for measuring axial length. AB - PURPOSE: To compare axial length (AL), anterior chamber depth (ACD), and keratometric (K) measurements of 2 laser biometers. SETTING: Private practices, Lynwood and Santa Monica, California, USA. METHODS: In this prospective comparative observational study of eyes with cataract and eyes with a clear lens, AL, ACD, and K measurements were performed using an IOLMaster biometer, which uses partial coherence interferometry (PCI), and a Lenstar LS 900 biometer, which uses optical low-coherence reflectometry (OLCR). Intraocular lens (IOL) power calculation was performed using the Haigis formula. The IOL prediction error was calculated for each eye. RESULTS: The study evaluated 50 eyes with cataract and 50 eyes with a clear lens. There was a good correlation between AL, ACD, and K measurements in the cataractous eyes (r = 0.9993, 0.9667, and 0.9959, respectively) and in eyes with a clear lens (r = 0.9995, 0.8211, and 0.9959, respectively). The OLCR unit measured a slightly longer AL in the cataract group and clear lens group (mean difference 0.026 mm and 0.023 mm, respectively), a deeper ACD (0.128 mm and 0.146 mm, respectively), and a flatter K (-0.107 diopter [D] and -0.121 D, respectively). The differences were statistically significant (P<.0001). The mean absolute error in IOL power prediction was 0.455 D +/- 0.32 (SD) with the OLCR unit and 0.461 +/- 0.31 D with the PCI unit (P>.1). CONCLUSIONS: Measurements were comparable between the OLCR device and the PCI device. A slight decrease (0.050) in the a(0) constant is recommended if the Haigis formula is used. PMID- 20362859 TI - Normative database of donor keratographic readings in an eye-bank setting. AB - PURPOSE: To generate a normative donor topographic database from rasterstereography images of whole globes acquired in an eye-bank setting with minimal manipulation or handling. SETTING: Eye-bank laboratory. METHODS: In a retrospective study, rasterstereography topographic images that had been prospectively collected in duplicate of donor eyes received by the Central Ohio Lions Eye Bank between 1997 and 1999 were analyzed. Best-fit sphere (BFS) and simulated keratometry (K) values were extracted. These values were recalculated after application of custom software to correct any tilt of the mapped surfaces relative to the image plane. The mean value variances between right eyes and left eyes, between consecutive scans, and after untilting were analyzed by repeated measures analysis of variance and t tests (P.05, Kolmogorov-Smirnov). There was no difference between right and left eyes or consecutive scans (P>.05). The mean values changed when the images were tilt corrected (P<.05). The right eye BFS, Kflat, and Ksteep values of 42.03 diopters (D) +/- 1.88 (SD), 42.21 +/- 2.10 D, and 43.82 +/- 2.00 D, respectively, increased to 42.52 +/- 1.73 D, 43.05 +/- 1.99 D, and 44.57 +/- 2.02 D, respectively, after tilt correction. CONCLUSIONS: Keratometric parameter frequency distributions from the donor database of tilt-corrected data were normal in distribution and comparable to parameters reported for normal eyes in a living population. These findings show the feasibility and reliability of routine donor-eye topography by rasterstereography. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. PMID- 20362860 TI - Effect of genipin collagen crosslinking on porcine corneas. AB - PURPOSE: To evaluate the effect of genipin, a natural crosslinker, on porcine corneas. SETTING: Department of Ophthalmology, Universidad Nacional de Colombia, Bogota, Colombia. METHODS: Corneal strips (12.0 mm x 2.3 mm) were harvested from porcine eyes and treated by incubation with genipin at concentrations of 1.00%, 0.25%, and 0.10%. Parallel corneal strips from the same eye were used as untreated controls. After treatment at 20 degrees C for 40 minutes, tensile strain measurements were performed in a biomaterial tester. Porcine button corneas were treated with genipin 0.25% for 15 minutes and then digested by bacterial collagenase. Treated and untreated corneas were evaluated by light microscopy. RESULTS: Young modulus and stiffness in treated corneas increased in a concentration-dependent manner. Genipin increased resistance to corneal collagenase 5-fold in comparison with the controls. A decrease in the interlamellar space in treated corneas was also observed. CONCLUSIONS: Corneal collagen crosslinking induced with genipin produced a significant increase in biomechanical strength and resistance to bacterial collagenase. This crosslinker could be useful in treating corneal ectasia and corneal infectious and noninfectious diseases involving corneal melting. PMID- 20362861 TI - Average focal length and power of a section of any defined surface. AB - PURPOSE: To provide a method to allow calculation of the average focal length and power of a lens through a specified meridian of any defined surface, not limited to the paraxial approximations. SETTING: University of Liverpool, Liverpool, United Kingdom. METHOD: Functions were derived to model back-vertex focal length and representative power through a meridian containing any defined surface. Average back-vertex focal length was based on the definition of the average of a function, using the angle of incidence as an independent variable. RESULTS: Univariate functions allowed determination of average focal length and power through a section of any defined or topographically measured surface of a known refractive index. These functions incorporated aberrations confined to the section. CONCLUSIONS: The proposed method closely approximates the average focal length, and by inference power, of a section (meridian) of a surface to a single or scalar value. It is not dependent on the paraxial and other nonconstant approximations and includes aberrations confined to that meridian. A generalization of this method to include all orthogonal and oblique meridians is needed before a comparison with measured wavefront values can be made. PMID- 20362862 TI - Negative dysphotopsia after temporal corneal incisions. AB - Temporal incisions made during cataract extraction have been purported to cause negative dysphotopsia. A case in which negative dysphotopsia occurred after superior scleral tunnel incisions is described. The dystopsia symptoms resolved immediately after intraocular lens exchange using temporal corneal incisions. PMID- 20362863 TI - Orbital cellulitis as complication of endophthalmitis after cataract surgery. AB - A 74-year-old man presented with light perception and presumed early bacterial endophthalmitis in the left eye after cataract surgery. Vitreous tap biopsy and core vitrectomy were performed immediately, along with injection of antibiotic agents (ceftazidime and vancomycin). Culture of the vitreous tap revealed Pseudomonas aeruginosa sensitive to ceftazidime. The eye remained inflamed despite 2 additional intravitreal ceftazidime injections. Orbital cellulitis with perforation of the globe was suspected and confirmed on magnetic resonance imaging, and enucleation was performed. Endophthalmitis due to P aeruginosa is associated with poor visual outcomes despite prompt treatment with appropriate intravitreal antibiotic agents. Progression to orbital cellulitis in immunocompetent patients is extremely rare. Careful monitoring of patients with endophthalmitis after cataract surgery is recommended. . PMID- 20362864 TI - Surface calcification of hydrophilic acrylic intraocular lens related to inflammatory membrane formation after combined vitrectomy and cataract surgery. AB - Two patients complained of blurred vision approximately 6 months after having combined vitrectomy and phacoemulsification with implantation of a C-flex 570C hydrophilic acrylic intraocular lens (IOL). Multiple granules were noted on the anterior surface of the IOLs in both patients. Intraocular lens exchange was performed in both eyes, and the explanted IOLs were sent for histopathological analysis. Scanning electron microscopy confirmed the presence of cracks and granules on the IOL surfaces and energy-dispersive x-ray spectroscopy demonstrated calcium deposition. Based on the calcification pattern on the anterior surface of the IOLs, 2 additional cases of opacification were identified under slitlamp examination. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 20362865 TI - Iris-fixated phakic intraocular lens implantation for correction of high myopia in microspherophakia. AB - We report the refractive correction of high myopia in a 23-year-old patient with idiopathic microspherophakia using iris-fixated phakic intraocular lenses (pIOLs) (Verisyse/Artisan). Four years after bilateral implantation, the uncorrected distance visual acuity was 20/25 with a correction of 20/20(-1) in both eyes. No intraoperative or postoperative complications occurred. Iris-fixated pIOLs are not recommended for every patient with microspherophakia. However, this procedure may be an option in microspherophakic patients with appropriate anterior chamber depth and no history of lens dislocation who are likely to comply with annual eye examinations. Follow-up should include monitoring the endothelial cell count and biomicroscopy for adequate space between the pIOL, the natural crystalline lens, and the corneal endothelium. Scheimpflug photography can be a valuable tool in such cases. PMID- 20362866 TI - Capsule contraction syndrome with haptic deformation and flexion. AB - We report a case series of capsule contraction syndrome in 5 eyes of 4 patients and describe a previously unreported complication: full flexion of the haptics onto the anterior surface of the optic. Haptics have been reported to slide anterior to the optic while remaining in their original coronal plane. As surgeons move to the use of preloaded injectable IOLs, it is important to scrutinize haptic-optic junction design and IOL material in the light of this complication. PMID- 20362867 TI - Use of 23-gauge or 25-gauge trocar cannula for globe maintenance in glued intraocular lens surgery. PMID- 20362868 TI - Phacoemulsification surgery in 105-year-old patients. PMID- 20362869 TI - A survey of the current role of manual extracapsular cataract extraction. PMID- 20362870 TI - Consultation section: Cataract surgical problem. PMID- 20362878 TI - Use of intracameral phenylephrine to manage iris prolapse. PMID- 20362881 TI - Intraocular surgery with warfarin anticoagulation. PMID- 20362883 TI - Intraepithelial flap creation during epi-LASIK. PMID- 20362884 TI - How quickly we forget. PMID- 20362885 TI - Possible causes for exposure of anterior chamber intraocular lens haptic tip. PMID- 20362887 TI - AAO research award winners recognized. PMID- 20362888 TI - Authors' response. Appearances count when industry underwrites research. PMID- 20362889 TI - Biomechanics of self-ligating brackets. PMID- 20362890 TI - Reproducibility of the CVM method: a reply. PMID- 20362892 TI - Soft-tissue considerations in mandibular setback. PMID- 20362894 TI - Changes in esthetic standards since 1940. AB - INTRODUCTION: The goals of this study were to investigate differences between the most popular female and male faces, past and present, and to determine whether they had changed over time and, if so, to what extent. METHODS: Internet film databases were searched for photographs of men and women who were considered attractive between 1940 and 2008. Images meeting defined inclusion criteria were compared. Measurements were taken on a minimum of 20 images per sex per decade. Intersex facial differences were grouped by decades, and we examined whether these differences remained stable or whether and how they changed over time. RESULTS: The women had fuller and more protrusive lip profiles than did the men, particularly during the first decade of the 21st century. Significant sex specific developments were noted over time with respect to chin lengths, frontonasal angles, and total face angles. The men had decreases in chin size and length, but a small opposite trend was observed in the women's faces. During the observation period, female and male faces considered highly attractive became slightly more similar in terms of chin position and size. CONCLUSIONS: Notions of facial attractiveness might be influenced by developments in society. PMID- 20362896 TI - Comparative study of 2 software programs for predicting profile changes in Class III patients having double-jaw orthognathic surgery. AB - INTRODUCTION: Computer software can be used to predict orthognathic surgery outcomes. The aim of this study was to subjectively compare the soft-tissue surgical simulations of 2 software programs. METHODS: Standard profile pictures were taken of 10 patients with a Class III malocclusion and a concave facial profile who were scheduled for double-jaw orthognathic surgery. The patients had horizontal maxillary deficiency or horizontal mandibular excess. Two software programs (Dentofacial Planner Plus [Dentofacial Software, Toronto, Ontario, Canada] and Dolphin Imaging [version 9.0, Dolphin Imaging Software, Canoga Park, Calif]) were used to predict the postsurgical profiles. The predictive images were compared with the actual final photographs. One hundred one orthodontists, oral-maxillofacial surgeons, and general dentists evaluated the images and were asked whether they would use either software program to plan treatment for, or to educate, their patients. RESULTS: Statistical analyses showed differences between the groups when each point was judged. Dolphin Imaging software had better prediction of nasal tip, chin, and submandibular area. Dentofacial Planner Plus software was better in predicting nasolabial angle, and upper and lower lips. The total profile comparison showed no statistical difference between the softwares. CONCLUSIONS: The 2 types of software are similar for obtaining 2-dimensional predictive profile images of patients with Class III malocclusion treated with orthognathic surgery. PMID- 20362898 TI - Morphologic, functional, and occlusal characterization of mandibular lateral displacement malocclusion. AB - INTRODUCTION: Mandibular lateral displacement (MLD) is clinically characterized by deviation of the chin, facial asymmetry, dental midline discrepancy, crossbite in the posterior region, and high prevalence of internal derangement of the temporomandibular joint. Morphologic and functional characteristics of MLD should be clarified to correct and prevent this malocclusion. METHODS: We examined the morphologic features, occlusal scheme, and functional behavior of MLD in 116 patients. Facial morphology was examined with posteroanterior cephalograms, occlusion guidance on the articulator after face-bow transfer, and condylar movement with the condylograph. RESULTS: The superiorly inclined occlusal plane was associated with mandibular deviation in the same direction. The posterior occlusal plane on the shifted side was significantly steeper than that on the nonshifted side. Functional analysis of condylar movement showed a close relationship between the direction of MLD and the direction of condylar lateral shift during opening and closing, and protrusion and retrusion. The occlusal guidance inclination in the buccal segment of the nonshifted side was steeper than that in the shifted side. CONCLUSIONS: The results suggested that reduced vertical height of the dentition on 1 side induced mandibular lateral adaptation with contralateral condylar shift (asymmetry); this leads to condylar lateral shift during functional movement. PMID- 20362900 TI - Analysis of intra-arch and interarch measurements from digital models with 2 impression materials and a modeling process based on cone-beam computed tomography. AB - INTRODUCTION: Study models are an essential part of an orthodontic record. Digital models are now available. One option for generating a digital model is cone-beam computed tomography (CBCT) scanning of orthodontic impressions and bite registrations. However, the accuracy of digital measurements from models generated by this method has yet to be thoroughly evaluated. METHODS: A plastic typodont was modified with reference points for standardized intra-arch and interarch measurements, and 16 sets of maxillary and mandibular vinylpolysiloxane and alginate impressions were made. A copper wax-bite registration was made with the typodont in maximum intercuspal position to accompany each set of impressions. The impressions were shipped to OrthoProofUSA (Albuquerque, NM), where digital orthodontic models were generated via CBCT. Intra-arch and interarch measurements were made directly on the typodont with electronic digital calipers and on the digital models by using OrthoProofUSA's proprietary DigiModel software. RESULTS: Percentage differences from the typodont of all intra-arch measurements in the alginate and vinylpolysiloxane groups were low, from 0.1% to 0.7%. Statistical analysis of the intra-arch percentage differences from the typodont of the alginate and vinylpolysiloxane groups had a statistically significant difference between the groups only for maxillary intermolar width. However, because of the small percentage differences, this was not considered clinically significant for orthodontic measurements. Percentage differences from the typodont of all interarch measurements in the alginate and vinylpolysiloxane groups were much higher, from 3.3% to 10.7%. Statistical analysis of the interarch percentage differences from the typodont of the alginate and vinylpolysiloxane groups showed statistically significant differences between the groups in both the maxillary right canine to mandibular right canine (alginate with a lower percentage difference than vinylpolysiloxane) and the maxillary left second molar to mandibular left second molar (alginate with a greater percentage difference than vinylpolysiloxane) segments. This difference, ranging from 0.24 to 0.72 mm, is clinically significant. CONCLUSIONS: In this study, digital orthodontic models from CBCT scans of alginate and vinylpolysiloxane impressions provided a dimensionally accurate representation of intra-arch relationships for orthodontic evaluation. However, the use of copper wax-bite registrations in this CBCT-based process did not result in an accurate digital representation of interarch relationships. PMID- 20362902 TI - Fluoride release from an orthodontic glass ionomer adhesive in vitro and enamel fluoride uptake in vivo. AB - INTRODUCTION: The objective of this study was to investigate the in-vitro fluoride release from a glass ionomer orthodontic bonding system (Fuji I, GC Corporation, Tokyo, Japan) over a 2-month period and the in-vivo enamel fluoride uptake after 6 months. METHODS: Ten metal brackets were bonded with either glass ionomer or composite resin (Transbond XT, 3M Unitek, Monrovia, Calif; Light Cure), which served as controls, to recently extracted molars. The bonded teeth, cut at the level of their roots, were stored in distilled water that was renewed after every fluoride measurement at 1, 3, 7, 30, and 60 days. The in-vitro fluoride release was measured by using a fluoride ion-selective electrode, connected to an ion analyzer. Fifteen pairs of premolars were bonded with metal brackets with either the Fuji or the Transbond adhesive. Six months later, the teeth were extracted for orthodontic purposes, embedded in resin, and cross sectioned, and the fluoride compositions between the outer and bulk enamel surfaces were evaluated with scanning electron microscopy and energy dispersive analysis. The results were analyzed with nonparametric 1-way analysis of variance (ANOVA) on ranks for in-vitro fluoride release and nonparametric 2-way ANOVA on ranks for in-vivo fluoride enamel uptake; group differences were investigated with the Holm-Sidak test at the .05 level. The Spearman rank correlation coefficient test was used to investigate the association between fluoride and aluminum levels in the interfaces of the specimens bonded. RESULTS: The initial burst of fluoride release observed for the Fuji adhesive after the first day of the experiment had a significant decrease with time, and it persisted throughout the monitoring period (60 days) (P <0.05). Fluoride concentrations were found in both the outer and deeper enamel surfaces, with the outer sites having 4 times higher fluoride relative to the bulk for the glass ionomer (P <0.05), and higher fluoride was found in the outer layers for the glass ionomer bonded enamel specimens (P <0.05). However, the concurrent identification of aluminum and fluoride traces in the enamel implied that the source of this high fluoride concentration originated from cement particles and not from ionic uptake. CONCLUSIONS: The short-term fluoride release and the absence of documented enamel uptake suggest that the glass ionomer orthodontic adhesive tested might provide protective action only through the reservoir mechanism. PMID- 20362905 TI - Root resorption associated with orthodontic tooth movement: a systematic review. AB - INTRODUCTION: This systematic review evaluated root resorption as an outcome for patients who had orthodontic tooth movement. The results could provide the best available evidence for clinical decisions to minimize the risks and severity of root resorption. METHODS: Electronic databases were searched, nonelectronic journals were hand searched, and experts in the field were consulted with no language restrictions. Study selection criteria included randomized clinical trials involving human subjects for orthodontic tooth movement, with fixed appliances, and root resorption recorded during or after treatment. Two authors independently reviewed and extracted data from the selected studies on a standardized form. RESULTS: The searches retrieved 921 unique citations. Titles and abstracts identified 144 full articles from which 13 remained after the inclusion criteria were applied. Differences in the methodologic approaches and reporting results made quantitative statistical comparisons impossible. Evidence suggests that comprehensive orthodontic treatment causes increased incidence and severity of root resorption, and heavy forces might be particularly harmful. Orthodontically induced inflammatory root resorption is unaffected by archwire sequencing, bracket prescription, and self-ligation. Previous trauma and tooth morphology are unlikely causative factors. There is some evidence that a 2 to 3 month pause in treatment decreases total root resorption. CONCLUSIONS: The results were inconclusive in the clinical management of root resorption, but there is evidence to support the use of light forces, especially with incisor intrusion. PMID- 20362904 TI - Mandibular condylar cartilage response to moving 2 molars in rats. AB - INTRODUCTION: The purpose of this study was to investigate the responses of mandibular condylar cartilage to moving 2 molars in different combinations. METHODS: Rats were assigned to male and female control and experimental groups (each, n = 5). Elastic rubber bands were used to move medially the maxillary left and the mandibular right first molars in experimental group I. The same method was used to distally move the maxillary left and the mandibular right third molars, 2 mandibular third molars, and 2 maxillary third molars in experimental groups II, III, and IV, respectively. At the end of the eighth week, all condyles were examined histologically. The areas of histologic change as a percentage of total cartilage area were compared by using the Mann-Whitney U test. RESULTS: Cartilage degenerative remodeling was observed in experimental groups II, III, and IV. The percentage areas of degenerative remodeling were higher in female experimental groups II and III than in the female control group, and in female experimental group II than in female experimental group IV and male experimental group II (all, P <0.05). CONCLUSIONS: The mandibular condylar cartilage of female rats responded variously to different combinations of molar movement; the most obvious remodeling was observed in groups in which the maxillary left and mandibular right third molars were moved. PMID- 20362906 TI - Repair of root resorption 2 to 16 weeks after the application of continuous forces on maxillary first molars in rats: a 2- and 3-dimensional quantitative evaluation. AB - INTRODUCTION: Root resorption is a side effect of orthodontic treatment that occurs with the removal of hyalinized tissue. Studies have shown that a reparative process in the periodontium begins when the applied orthodontic force is discontinued or reduced below a certain level. However, quantitative 3 dimensional evaluation of root resorption repair has not been done. The aim of this study was to quantitatively assess the 2- and 3-dimensional changes of root resorption craters after 2 weeks of continuous mesially applied orthodontic forces of 50 g on rat molars and 2- to 16-week retention periods. METHODS: We used 60 male Wistar rats (10 weeks old). Nickel-titanium closed-coil springs were used to apply 50-g mesial forces for 2 weeks to move the maxillary left first molars. The rats were randomly allocated to 6 groups. Those in the zero-week retention group were killed after force application. In the remaining 5 groups, the interdental spaces between the maxillary first and second molars were filled with resin to retain the molars. The molars were extracted after periods of retention from 2 and 16 weeks. The maxillary right molars were used as the controls. Mesial and distal roots (distobuccal and distopalatal) were examined by using scanning electron and 3-dimensional scanning laser microscopes. The surface area, depth, volume, and roughness of the root resorption craters were measured. RESULTS: The area, depth, and volume of the craters decreased gradually and showed similar trends over the retention time, approaching a plateau at the 12th week. After 16 weeks of retention, the volumes of the resorption craters of the distobuccal and distopalatal roots reached recovery peaks of 69.5% and 66.7%, respectively. Small pits on the mesial roots showed recovery of 62.5% at the 12th week. The healing patterns in distal roots with severe resorption and mesial roots with shallow resorption had no significant differences. CONCLUSIONS: The resorption and repair processes during the early stages of retention are balanced, and most of the reparative process occurs after 4 weeks of passive retention after the application of orthodontic force. Frequent orthodontic reactivations should be avoided to allow recovery and repair of root surface damage. PMID- 20362907 TI - Modifications of midpalatal sutural density induced by rapid maxillary expansion: A low-dose computed-tomography evaluation. AB - INTRODUCTION: The aim of this study was to evaluate the density of the midpalatal suture as assessed by low-dose computed tomography (CT) before rapid maxillary expansion (RME) (T0), at the end of active expansion (T1), and after a retention period of 6 months (T2). METHODS: The study sample comprised 17 prepubertal subjects (mean age, 11.2 years) with constricted maxillary arches and unilateral or bilateral posterior crossbite. The total amount of expansion was 7 mm in all subjects. Multi-slice low-dose CT scans were taken at T0, T1, and T2. On axial CT scanned images, 4 regions of interest (ROIs) were placed along the midpalatal suture (anterior [AS ROI] and posterior [PS ROI]) and in 2 regions of palatal bone (anterior and posterior). Density was measured in Hounsfield units. The Mann Whitney U test and Friedman analysis of variance (ANOVA) with post-hoc test were used (P <0.05). RESULTS: The densities in the AS and PS ROIs were significantly smaller than the reference bone densities before RME therapy. Both AS and PS ROIs showed significant decreases in density from T0 to T1, significant increases from T1 to T2, and no significant differences from T0 to T2. CONCLUSIONS: The effective opening of the midpalatal suture by RME in prepubertal subjects was associated with a significant decrease in sutural density. The sutural density after 6 months of retention post-RME indicated reorganization of the midpalatal suture, since it showed values similar to the pretreatment ones. PMID- 20362908 TI - Surface characteristics of orthodontic adhesives and effects on streptococcal adhesion. AB - INTRODUCTION: In this study, we analyzed the surface roughness (SR) and surface free energy (SFE) characteristics of various orthodontic adhesives and their effects on the adhesion of mutans streptococci (MS). METHODS: Three nonfluoride releasing composites, 1 fluoride-releasing composite, 1 polyacid-modified composite (compomer), and 2 resin-modified glass ionomers (RMGIs) were analyzed with confocal laser scanning microscopy and the sessile drop method. Each material was incubated with whole saliva or phosphate-buffered saline solution. Adhesion assays were then performed by incubating each material with tritium labeled cariogenic streptococci. RESULTS: We found that SFE and its components were significantly different among the adhesives, despite relatively uniform SR. RMGIs showed significantly higher SFE-particularly, dispersive, polar, and acidic characteristics-than did the composites. The compomer had intermediate characteristics between the composites and RMGIs. MS adhered to RMGIs significantly more than to the composites and the compomer, but there was no significant difference among the composites. The longer incubation time increased MS adhesion, whereas saliva coating did not significantly influence MS adhesion. There was a correlation between SFE and MS adhesion. SFE and its dispersive, polar, and acid components significantly influenced MS adhesion irrespective of saliva coating. CONCLUSIONS: This study suggests that initial MS adhesion is significantly influenced by SFE characteristics of adhesives rather than SR or saliva coating. PMID- 20362909 TI - Potential of self-drilling orthodontic microimplants under immediate loading. AB - INTRODUCTION: The aim of this study was to investigate clinically and histologically the efficiency of self-drilling microimplants as orthodontic anchorage with immediate, continuous, and constant loadings. METHODS: Titanium alloy microimplants with diameters of 1.2 to 1.3mm were manually placed into the buccal sides of both jaws, including the interradicular areas, in 3 dogs. Implants were placed without predrilling in thin cortical bone areas; in thick cortical bone areas, a 2-mm deep pilot hole was drilled. Thirty-six microimplants, subjected to approximately 200g of immediate horizontal loading, served as the study group. The remaining 8 received no loading and were the controls over the 9-week observation period. The distances of reciprocally loaded microimplants and crevicular pockets were measured at the beginning and end of loading. Serially undecalcified and decalcified sections of the microimplants and surrounding tissues were studied with light and fluorescent microscopes. After 9 weeks of observation, 22 fixtures were easily removed with a screwdriver. Two were broken, and 1 was movable. RESULTS: Histologic analysis showed good osseointegration in all stable samples, and new bone formation and bone apposition to the surface of the threads in loaded and unloaded samples. Histomorphometric evaluation showed high bone-to-implant contact values in the loaded samples, but no significant statistical differences from the unloaded ones. CONCLUSIONS: Titanium alloy microimplants with small diameters (1.2-1.3mm) are strong enough for self-drilling and immediate loading in thin cortical bone areas, but, to reduce the chance of breakage, a drilling of a pilot hole is suggested in thick cortical bone areas. PMID- 20362910 TI - Prediction of the mesiodistal width of unerupted permanent canines and premolars: a statistical approach. AB - INTRODUCTION: Prediction of the mesiodistal width of unerupted permanent canines and premolars is of major interest for orthodontic diagnosis and treatment planning. METHODS: To improve the accuracy of the prediction, we looked for the best combination of independent variables with multiple linear regression. RESULTS: The most accurate prediction was obtained for the combination of the mandibular right first molar and lateral incisor, and the maxillary left central incisor. Adding to the regression equation 1 erupted canine or premolar improved the accuracy of the prediction considerably. Because of the variable character of the eruption sequence during the second transitional period, a separate regression model for every canine or premolar was necessary. The precision of our new method and other methods from the literature was tested in a separate study group. CONCLUSIONS: The results of this study show that our prediction method of the mesiodistal crown diameters of unerupted canines and premolars during the dental transition is accurate. A computer program was developed for user-friendly clinical application. PMID- 20362911 TI - Effects of premolar extractions on Bolton overall ratios and tooth-size discrepancies in a Japanese orthodontic population. AB - INTRODUCTION: The purpose of this study was to investigate the effects of premolar extractions on the Bolton overall ratios and overall tooth-size discrepancies in a Japanese orthodontic population. METHODS: Mesiodistal tooth widths were measured on 198 pretreatment dental casts of subjects with Class I, Class II, and Class III malocclusions. The overall ratios and tooth-size discrepancies were determined before and after hypothetical premolar extractions. Before and after extractions, the subjects were divided into small, normal, and large overall ratio groups categorized by the Bolton standard deviation definition, and into small, normal, and large correction groups by the actual amount of change calculated for tooth-size correction in millimeters. Extractions were performed in the following combinations: (1) all first premolars, (2) all second premolars, (3) maxillary first and mandibular second premolars, and (4) maxillary second and mandibular first premolars. For statistical evaluations, analysis of variance, Kruskal-Wallis, Friedman, Scheffe, Bonferroni, and Tukey tests were performed. RESULTS: The overall ratios decreased in every malocclusion group after extraction of any combination of premolars. The decreases were significantly notable in combinations 2 and 4. Some subjects in the normal overall ratio and maxillary and mandibular correction groups moved into the clinically significant tooth-size discrepancy group after premolar extraction, and the reverse was also true. CONCLUSIONS: In formulating a treatment plan involving premolar extractions, orthodontists should consider that the overall ratios might decrease, and normal and clinically significant tooth-size discrepancies could change mutually after extractions. PMID- 20362912 TI - Does a transverse maxillary deficit affect the cervical vertebrae? A pilot study. AB - INTRODUCTION: The aim of this pilot study was to analyze the morphology of the cervical vertebrae of subjects with transverse maxillary constriction. METHODS: The study population included 40 subjects (7-11 years of age) undergoing palatal expansion to correct transverse maxillary constriction, and a control group of 40 subjects (7-11 years of age) without transverse maxillary constriction. Two observers assessed cervical morphology on lateral cephalograms by means of templates showing cervical maturation sequences. Round angles and concave vertebral body edges were classified as vertebral anomalies that could not be associated with physiologic vertebral growth. Agreement between the data collected by the observers was assessed with the Cohen kappa test, and the data of the 2 groups were compared with the Fisher exact test (P <0.05). RESULTS: The 2 observers agreed in their assessments (k >0.5). The greater percentage of vertebral defects in the study group was significant (P <0.05) according to both observers. Rounding of the anterosuperior angle of the vertebral body was the most common defect in the study group. Vertebral defects of the study group were mainly at vertebrae C4 and C5. CONCLUSIONS: A statistically significant correlation, worthy of further study, was found between transverse maxillary constriction and cervical vertebral defects. PMID- 20362913 TI - Commercially available archwire forms compared with normal dental arch forms in a Japanese population. AB - INTRODUCTION: The objective of this research was to evaluate commercially available preformed archwire forms compared with normal dental arch forms. METHODS: Thirty mandibular dental casts were made of orthodontically untreated subjects with the most ideal occlusions, selected from among approximately 3500 students at Nippon Dental University. Canine and first-molar widths were measured on the dental casts with a 3-dimensional laser scanning system. Twenty preformed mandibular archwires were scanned by using a flatbed scanner. The archwire widths were measured at the level of the mean canine and first-molar depths, and then compared with the natural dental arch widths, considering bracket thickness, measured with a modified caliper. The results were statistically analyzed with the Mann-Whitney test. RESULTS: The preformed archwires that most closely matched the normal dental arch forms were the Orthos (Ormco, Glendora, Calif) and Vari Simplex large (Ormco) types. The preformed archwires were significantly narrower than the normal dental arches at both the canine (P <0.05) and molar (P <0.01) levels. CONCLUSIONS: The variations in current preformed archwires do not correspond entirely with various arch forms in a group with ideal occlusion. The most commonly used archwires are similar and can be considered imitations of the Roth arch form, which was designed primarily for extraction patients in the 1970s. Therefore, preformed archwires that are approximately 1 to 3 mm wider at the canine level and 2 to 5 mm wider at the first-molar level might be required for today's orthodontic needs. PMID- 20362914 TI - Bond strength of orthodontic brackets with new self-adhesive resin cements. AB - INTRODUCTION: In this investigation, we determined the shear bond strength (SBS) of metallic and ceramic orthodontic brackets with new self-adhesive cements. METHODS: One hundred extracted premolars were used. They were sterilized and their roots embedded in stone bases, with the facial surfaces perpendicular to the bottom of the bases. The teeth were divided into 2 main groups, to receive metallic or ceramic brackets (Victory series 3M Unitek, Monrovia, Calif). In each group, the specimens were further divided into 5 subgroups according to the cement used: an etch-and-rinse control, Transbond-XT (3M Unitek); a resin cement with self-etch primer, Esthetic Cement system NC-100, (Kuraray, Okayama, Japan); and 3 self-adhesive resin cements: Rely-X Unicem (3M ESPE, Seefeld, Germany), Biscem DC (Bisco, Schaumburg, Ill), and Breeze (Pentron, Wallingford, Conn). Ten brackets were cemented in each subgroup. The specimens were stored in distilled water at 37 degrees C for 7 days and subjected to 3000 thermocycles between 5 degrees C and 55 degrees C. The brackets were then debonded in shear with a testing machine. RESULTS: Mean values for the metallic brackets cemented with Transbond XT, Esthetic Cement system, Rely-X Unicem, Biscem DC, and Breeze were 18.6, 6.0, 6.0, 2.2, and 8.4 MPa, respectively. For the ceramic brackets, the values were 22.7, 17, 7.7, 1.6, and 9.5 MPa, respectively. Analysis of variance (ANOVA) showed significant differences among the subgroups (P <0.05) for both bracket types. For the ceramic brackets, the Tukey test showed no statistical difference in mean SBS between Transbond XT and Esthetic Cement system. CONCLUSIONS: The SBS values of brackets cemented with etch-and-rinse cement were significantly higher than those of the 3 self-adhesive cements. However, when the self-etch adhesive, Esthetic Cement system, was used with ceramic brackets, no significant difference was found in the SBS compared with Transbond XT (P = 0.052). PMID- 20362915 TI - Microleakage of orthodontic band cement at the cement-enamel and cement-band interfaces. AB - INTRODUCTION: Our objective was to determine and compare microleakage patterns of conventional glass ionomer cement (GIC), resin modified GIC (RMGIC), and polyacid modified composite for band cementation. METHODS: Sixty freshly extracted third molars were randomly divided into 3 groups of 20 teeth each. Microetched molar bands in the 3 groups were cemented to enamel with one of three orthodontic cements: Ketac-Cem (3M ESPE, Gmbh, Seefeld, Germany), Multi-Cure (3M Unitek, Monrovia, Calif), and Transbond Plus (3M Unitek). A dye penetration method was used for microleakage evaluation. Microleakage was determined by a stereomicroscope for the cement-band and cement-enamel interfaces from both the buccal and lingual margins. Statistical analysis was performed with Kruskal Wallis and Mann-Whitney U tests. RESULTS: The buccal sides had similar microleakage values compared with the lingual sides for the cement-enamel and cement-band interfaces with all cements. Statistical comparisons showed statistically significant differences among the band cements between both interfaces (P <0.001). When the cement systems were compared, conventional GIC showed the highest leakage scores between cement-band (median, 3.50 mm) and cement-enamel (median, 2.88 mm) interfaces. Teeth banded with RMGIC and modified composite showed similar microleakage scores, and both had less leakage (<1 mm) than conventional GIC. CONCLUSIONS: Conventional GIC is associated with more microleakage than RMGIC and modified composite at both the cement-band and cement enamel interfaces. PMID- 20362916 TI - Use of rhythmic wire system with miniscrews to correct occlusal-plane canting. AB - Occlusal-plane canting is a challenging problem for orthodontists because it cannot be solved easily without surgical intervention. Normally, a LeFort I osteotomy and concomitant mandibular surgery is used to correct the problem, even in patients with mild facial asymmetry but with noticeable occlusal-plane canting. Skeletal anchorage can be used in patients with occlusal canting to reduce the need for orthognathic surgery. The purpose of this article was to introduce a biomechanical system-rhythmic wire- to correct occlusal-plane canting. The records of 2 patients treated with this system are shown. PMID- 20362917 TI - Oral appliance treatment for obstructive sleep apnea in a partly edentulous patient. AB - INTRODUCTION: We report on the use of an oral appliance fitted to a few maxillary and mandibular teeth to treat obstructive sleep apnea syndrome. METHODS: We used a mandibular repositioning appliance, the adjustable PMPositioner. Polysomnograms were taken before and after use of the appliance. RESULTS: The apnea-hypopnea index decreased from 19.0 to 8.0. Minimum oxygen saturation increased from 80.0% to 86.0%, and rapid eye movement sleep increased from 6.0% to 20.0%, indicating that the device remained in position during sleep. A 2-year follow-up showed that periodontal and gingival health was maintained. CONCLUSIONS: Oral appliances such as the PMPositioner are an alternative for treating obstructive sleep apnea in partly edentulous patients. PMID- 20362918 TI - Elimination of transverse dental compensation is critical for treatment of patients with severe facial asymmetry. AB - This case report describes the importance of eliminating transverse dental compensation during preoperative orthodontic treatment for a patient with severe facial asymmetry. The patient, a 17-year-old Japanese woman, had severe facial asymmetry involving the maxilla and the mandible, and extreme transverse dental compensation of the anterior and posterior teeth in both arches. Therefore, the main treatment objectives were elimination of the transverse dental compensation by orthodontic treatment and correction of the morphology of the maxilla and the mandible by orthognathic surgery. The preoperative orthodontic treatment resulted in sufficient elimination of the transverse dental compensation and movement of the teeth into their proper positions so that basal bone firmly supported them. LeFort I osteotomy and sagittal split ramus osteotomy were performed to correct the skeletal morphology. Facial asymmetry was dramatically improved, and a favorable occlusion was obtained. At 1 year 8 months after the surgical orthodontic treatment, the facial symmetry and occlusion remained favorable. The results suggest that sufficient elimination of transverse dental compensation in the maxillary and mandibular arches during preoperative orthodontic treatment is requisite for successful treatment of severe facial asymmetry. PMID- 20362919 TI - Interview with the editor: David L. Turpin by Robert P. Scholz. AB - David L. Turpin has worked on dental journals for over 30 years--from his early days on the Pacific Coast Society of Orthodontists Bulletin, to the Angle Orthodontist, and to the American Journal of Orthodontics and Dentofacial Orthopedics. He will retire as editor-in-chief of the American Journal of Orthodontics and Dentofacial Orthopedics at the end of 2010. PMID- 20362920 TI - Research and education: the cornerstones of our mission. PMID- 20362921 TI - Addressing the clinical question. PMID- 20362922 TI - Basic perioperative transesophageal echocardiography: an education opportunity and a dilemma. PMID- 20362923 TI - Molecular imaging of vascular phenotype in cardiovascular disease: new diagnostic opportunities on the horizon. PMID- 20362924 TI - Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. AB - The authors summarize the recent developments in speckle-tracking echocardiography (STE), a relatively new technique that can be used in conjunction with two-dimensional or three-dimensional echocardiography for resolving the multidirectional components of left ventricular (LV) deformation. The tracking system is based on grayscale B-mode images and is obtained by automatic measurement of the distance between 2 pixels of an LV segment during the cardiac cycle, independent of the angle of insonation. The integration of STE with real-time cardiac ultrasound imaging overcomes some of the limitations of previous work in the field and has the potential to provide a unified framework to more accurately quantify the regional and global function of the left ventricle. STE holds promise to reduce interobserver and intraobserver variability in assessing regional LV function and to improve patient care while reducing health care costs through the early identification of subclinical disease. Following a brief overview of the approach, the authors pool the initial observations from clinical studies on the development, validation, merits, and limitations of STE. PMID- 20362925 TI - Immediate and long-term echocardiographic findings after transcatheter aortic valve implantation for the treatment of aortic stenosis: the Cribier Edwards/Edwards-Sapien valve experience. AB - BACKGROUND: The role of transcatheter aortic valve implantation in the treatment of calcific aortic stenosis is evolving. Immediate and long-term echocardiographic findings are poorly reported. METHODS: Eighty-eight patients in whom surgical aortic valve replacement was contraindicated were studied before and 1 and 7 days, 1 month, and 1 and 2 years after the transcatheter procedure by echocardiography for hemodynamic. Transaortic pressure gradient, permeability index, and aortic valve area were measured, and aortic regurgitation was estimated from a multiparametric approach. A subset group of 36 patients (23-mm valve, n = 18; 26-mm valve, n = 18) with optimal ultrasound window were investigated for valve geometry at 7 days. We measured the sphericity index (anteroposterior to sagittal diameter ratio) and the angulation of the prosthesis with the ascending aorta. RESULTS: By analysis of variance, transaortic pressure gradient significantly decreased and aortic valve area increased after the procedure (P < .0001 and P < .0001 respectively). Aortic regurgitation severity tended to decline at follow-up (P = .20) and was unaffected by valve size (P = .35). Leaks were paraprosthetic in 77% of cases, intraprosthetic in 6% of cases, and both in 17% of cases. Overall, the sphericity index was 1.03 +/- 0.07 and the angulation was 2.9 +/- 1.1 degrees. CONCLUSION: Echocardiography aids in the demonstration of appropriate prosthesis function and positioning after transcatheter aortic valve implantation. PMID- 20362926 TI - Transcutaneous aortic valve implantation--a first line treatment for aortic valve disease? PMID- 20362927 TI - Validation of conventional and simplified methods to calculate projected valve area at normal flow rate in patients with low flow, low gradient aortic stenosis: the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. AB - BACKGROUND: It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVA(proj)), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVA(proj) in a large series of patients and to propose a new clinically applicable simplified method to estimate AVA(proj). METHODS: AVA(proj) was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVA(proj) = AVA(rest) + slope x (250 - Q(rest)). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q. RESULTS: There was a strong correlation between AVA(proj) calculated by the two methods (r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVA(proj) demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVA(proj) < or = 1 cm(2), 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVA(proj) correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVA(proj) < or = 1.2 cm(2) (hazard ratio, 1.65; P = .02) and simplified AVA(proj) < or = 1.2 cm(2) (hazard ratio, 2.70; P < .0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive. CONCLUSION: In patients with low flow AS, AVA(proj) better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVA(proj) is easier to calculate than conventional AVA(proj), facilitating the use of AVA(proj) in clinical practice. PMID- 20362928 TI - Preoperative longitudinal left ventricular function by tissue Doppler echocardiography at rest and during exercise is valuable in timing of aortic valve surgery in male aortic regurgitation patients. AB - BACKGROUND: The aim of this study was to evaluate if left ventricular (LV) systolic function by tissue Doppler echocardiography at rest and during exercise preoperatively could predict postoperative LV function and thereby be useful in the timing of aortic valve surgery in patients with severe aortic regurgitation. METHODS: In 29 patients (median age, 59 years; interquartile range, 39-64 years), echocardiography, tissue Doppler echocardiography, and radionuclide ventriculography were performed preoperatively and postoperatively at rest and during supine bicycle exercise. RESULTS: Preoperative ejection fraction (EF) was 62%. Patients formed two groups, with basal LV peak systolic velocity (PSV) 5.9 cm/s preoperatively as the cutoff value between low and high PSV. Preoperatively, patients with low PSV had lower PSV during exercise (P < .005), EF during exercise (P < .05), and atrioventricular plane displacement (AVPD) at rest (P < .005) and during exercise (P < .05) than those with high PSV. Postoperatively, patients with low PSV had smaller AVPD at rest (P < .05), AVPD during exercise (P < .01), and PSV during exercise (P < .01). CONCLUSION: In patients with chronic aortic regurgitation with EFs and LV dimensions not fulfilling criteria for surgery according to guidelines, preoperative PSV and AVPD at rest and during exercise detected postoperative LV dysfunction. PMID- 20362929 TI - Infectious endocarditis: still a menace. PMID- 20362930 TI - Echocardiography: an important tool for cardiovascular risk assessment. PMID- 20362931 TI - Obfuscation, revisited. PMID- 20362932 TI - Health care reform in the postrecession economy. PMID- 20362933 TI - The problem with CER. PMID- 20362934 TI - Saving lives: mammograms, breast cancer, and health insurance reform. PMID- 20362935 TI - The age of (over)discovery. PMID- 20362936 TI - Hail Massachusetts. PMID- 20362937 TI - Early experience with electronic critical test identification, tracking, and documentation from within the PACS interface. PMID- 20362938 TI - Cloud computing: what is it and could it be useful? PMID- 20362939 TI - ACR appropriateness criteria on obstructive voiding symptoms secondary to prostate disease. AB - Obstructive voiding symptoms are most commonly due to prostatic hyperplasia, but other causes include bladder neck contractures, prostatic carcinomas, neurogenic bladder, and urethral stricture. Symptoms include hesitancy, dribbling, decreased force of stream, and postvoid fullness. Imaging is useful in evaluating the presence and degree of hydronephrosis, estimation of renal function, evaluation of the bladder and prostate, and detection of incidental upper tract malignancies or stones. Various modalities have been used for evaluation of the cause of obstruction. Literature on the indications and usefulness of these radiologic studies for obstructive voiding symptoms in different clinical settings is reviewed. PMID- 20362940 TI - The recent US preventive services task force guidelines are not supported by the scientific evidence and should be rescinded. AB - The recent US Preventive Services Task Force (USPSTF) guidelines on mammographic screening ignore the scientific evidence and should be rescinded. There are no data to support the age of 50 years as a threshold for screening. There are no data to support screening women aged 40 to 49 years on the basis of risk. The USPSTF failed to understand the randomized controlled trials and used the lowest possible benefit in its calculations. The death rate from breast cancer has decreased by 30%, primarily because of screening. The agency ignored direct data with regard to decreasing deaths in real populations in favor of computer models. The USPSTF admits that its guidelines will result in unnecessary deaths from breast cancer that could be avoided by screening annually beginning at the age of 40 years. PMID- 20362941 TI - Quality of life and diagnostic imaging outcomes. AB - The US Preventive Services Task Force recently promulgated revised guidelines for screening mammography. Criticisms were related to the undervaluation of future lives saved and the overvaluation of negative impacts of mammography. Radiologists downplayed quality-of-life factors, potentially understating the value of all imaging procedures. The task force's recommendations for core needle biopsy, based on similar conceptual frameworks, were not met with equivalent responses. Full appreciation of the costs and benefits of screening provides the basis for making the best decisions for individuals and populations. This is undermined by the mixed messages that patients and physicians receive during clinical encounters and through other means. Quantitative approaches to medical care are valid on their own terms and when evaluated in the individual context. Insights from behavioral economics and political science inform discussion of population-based medical interventions. Preventing harm from medical interventions satisfies both the "primum non nocere" dictum and the loss aversion heuristic concordantly. The most effective medical care is provided when benefits are maximized and complications are minimized, especially when the harms occur immediately and the benefits are delayed. The importance of both quality of life and longevity in health care decision making require minimizing negative impacts of mammography when screening low-risk populations. Current practice differs significantly from the successful randomized trials, front-loading costs of false positive examinations, and overtreatment. By decreasing false-positive mammographic results through adherence to ACR BI-RADS recommendations, radiologists can answer critics of early and frequent screening while still reducing cancer deaths. PMID- 20362942 TI - Patients imaged early during admission demonstrate reduced length of hospital stay: a retrospective cohort study of patients undergoing cross-sectional imaging. AB - PURPOSE: The aim of this study was to relate the early use of advanced imaging to length of hospital stay. MATERIALS AND METHODS: Among all 33,226 admissions to an urban tertiary care hospital in 2005, the authors identified the 10,005 admissions (30.1%) that included >or=1 advanced imaging study (CT, MRI, or nuclear scintigraphy) during the period from 1 day before admission (day -1) through discharge. The length of stay was calculated, and using the date of the first advanced imaging study performed relative to date of admission (date of service), the residual length of stay (length of stay minus date of service) of each admission was also calculated. For admissions of >or=3 days in duration, the mean length of stay of patients with early imaging (on day -1 or 0) was compared using t test to that of patients with later imaging (on day 1 or 2). For all admissions with advanced imaging, linear regression analysis was applied to length of stay and residual length of stay as a function of date of service. Similar analysis was performed on subgroups classified by examination type (modality and body part) and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code. RESULTS: The mean length of stay was significantly shorter for those imaged on day -1 or 0 compared with day 1 or 2 for all admissions of >or=3 days (8.6 vs 9.0 days, P = .015) and for the following specific subgroups: abdominal CT (8.4 vs 9.7 days, P = .003) and neurologic MR examination types (7.6 vs 8.7 days, P = .03) and abdominal ICD-9 codes (7.5 vs 8.8 days, P = .007). A statistically significant positive correlation was noted between length of stay and date of service for all admissions (slope, 0.27; P < .001) and for the following subgroups: neurologic CT, chest CT, abdominal CT, and nuclear scintigraphy examination types and abdominal ICD-9 codes. CONCLUSION: Early imaging with CT, MRI, or nuclear scintigraphy, particularly on the day before or the day of admission, was associated with significantly shorter lengths of stay of inpatients compared with patients who underwent advanced imaging later. PMID- 20362943 TI - Radiation passport: an iPhone and iPod touch application to track radiation dose and estimate associated cancer risks. AB - The rapid increase in the use of radiology and related exams and procedures has led to a concomitant increase in associated radiation risk. An application for the iPhone and iPod Touch called 'Radiation Passport' is described, which provides radiation dose estimates and associated cancer risks (non fatal and fatal) and serves as a method by which to track an individual's cumulative exposure. PMID- 20362944 TI - Patient access to radiology reports: what do physicians think? AB - PURPOSE: The aim of this study was to seek physicians' perspectives on radiology reporting systems, so that reporting systems can begin to be reorganized and made more patient centered by giving patients greater access to their personal health information. METHODS: Focus-group methodology was used to explore physicians' views on direct patient access to radiologic test results. Subjects for the two groups were physicians at a single academic medical center. Transcripts were analyzed using thematic content analysis. RESULTS: Most participants were dissatisfied with current reporting systems. Both radiologists and referring physicians (RPs) were aware that patients are not satisfied with the current system for notification of radiologic test results, and both thought that patients should have access to personal health information and take responsibility for their own health care. Regarding direct patient online access to results, both radiologists and RPs were concerned that patients would not understand report contents and that such access would lead to greater patient anxiety and demands on RPs' time. Referring physicians were also concerned that direct patient access to results would cause RPs to lose some control in the patient-physician relationship. Both radiologists and RPs preferred that any system for direct patient access incorporate a time delay and be tested for effect before being implemented. CONCLUSIONS: Revisions attempting to increase the patient-centeredness of care in the area of radiology reporting should be developed and tested to 1) minimize adverse effects on patient anxiety; 2) optimize timing, considering effects on both patients and RPs; and 3) simultaneously address problems with between-physician reporting methods. PMID- 20362945 TI - The breadth of teaching commitment in radiology departments: a national survey. AB - PURPOSE: The aim of this study was to investigate the teaching effort and associated resources across variously sized academic and nonacademic hospitals across the country. METHODS: A simple survey was constructed and distributed nationally to academic and nonacademic radiology departments of attending-level radiologists with residency programs. The survey queried human and financial resources used for education in the department or division in comparison with compensated human and financial resources for this effort. RESULTS: Sixty institutions across the country were surveyed, with 40 surveys returned from 35 unique institutions, representing a 67% response rate. All respondents reported performing teaching duties. The average teaching in departments was 30 hours per week, including teaching a wide scope of constituents, including trainees, colleagues, and allied staff members. The majority of teaching was spent on teaching medical students, residents, and fellows as well as referring physicians at multidisciplinary rounds. The commitment of dedicated full-time equivalent staff members and funding to teaching was limited, with 45% of respondents without dedicated full-time equivalents for teaching and just over 7% of the teaching funded. Eighty percent of institutions surveyed provided some amount of weekly academic time during which many staff members carried out their teaching preparations. CONCLUSIONS: Respondent radiology departments reported significant resource and manpower allocations to teaching efforts, in particular to trainees and referring physicians. However, limited compensation or incentives are allocated to this effort with regard to both human and financial resources. Compensated, allotted staff academic time may help offset the lack of dedicated educational resources to the teaching effort of radiology departments. PMID- 20362946 TI - The new radiology residency fourth year under the new curriculum: a survey of current residents' thoughts and suggestions about its design and purpose. AB - RATIONALE AND OBJECTIVES: The ABR announced changes to the board examinations for the resident class entering in 2010. These changes can allow the fourth year to be focused on subspecialization. During the restructuring process at the authors' institution, residents were queried about fourth-year design. The goal was to create a curriculum that would best meet residents' expectations while balancing clinical and educational needs. MATERIALS AND METHODS: Issues from the literature about the fourth-year curriculum were identified. An anonymous and voluntary survey based on these was developed and sent to 36 residents who made up the study group. Answers were reviewed for trends and significant unique responses before curricular development. RESULTS: Twenty-two of 36 residents (61%) responded. The most often selected electives were cardiac (91%), body MRI (77%), body interventional procedures (68%), neuroradiologic MRI (59%), musculoskeletal procedures (59%), and musculoskeletal imaging (54%). Fifty percent wanted 6 months in one area. Forty-five percent felt that the length of time in one area (most with a threshold of 9 months) would affect their decisions to pursue fellowships. The majority (73%) planned to use the fourth year to do rotations different from their planned fellowship areas. CONCLUSION: The majority of residents indicate that they would like to have at least half of their fourth year in one area, and most selected similar rotations to one another. The ability to do this extended time on one service may result in a decrease in the number of residents pursuing fellowships. However, most saw the fourth year as a way to broaden their radiologic knowledge. PMID- 20362947 TI - A suggested bookshelf for quality improvement in radiology. PMID- 20362948 TI - Leadership: style and structures. PMID- 20362949 TI - CMS adopts accreditation requirement for suppliers of advanced diagnostic imaging services. PMID- 20362950 TI - Web-based modules for the physics education of radiology residents. PMID- 20362951 TI - The national quality forum: how common sense becomes policy. PMID- 20362952 TI - William Angus. PMID- 20362953 TI - Re: "Beyond substance abuse: stress, burnout, and depression as causes of physician impairment and disruptive behavior". PMID- 20362955 TI - Re: "MR-guided focused ultrasound: a potentially disruptive technology". PMID- 20362957 TI - The wanderer At 12 weeks' gestation, the patient presented with abdominal pain and a palpable mass. PMID- 20362958 TI - Gastroschisis and intrauterine growth restriction. PMID- 20362959 TI - The role of kisspeptin signalling in the regulation of the GnRH-gonadotrophin ovarian axis in mice. AB - Kisspeptins are a series of overlapping peptides encoded by the Kiss1 gene that are required for central activation of the hypothalamic-pituitary-ovarian axis at puberty. Mutations that interfere with kisspeptin signalling prevent normal pubertal development in humans and mice. Mutations in the kisspeptin receptor GPR54, cause infertility and hypogonadotrophic hypogonadism in humans. The failure of the Gpr54 and Kiss1 mutant mice to ovulate has led to the suggestion that kisspeptin signalling may be required for the preovulatory luteinizing hormone (LH) surge. Although kisspeptin signalling has been shown to have an important central role in regulating the physiology of the ovary, the expression profile of Kiss1 and Gpr54 suggests that they may also have direct functions in the ovary and the placenta. PMID- 20362960 TI - [Fertility preservation before puberty: from mice to men]. AB - Malignant tumors account for 1% of childhood cancers. The incidence is to the order of 122 cases per million children. The five-year survival after cancer before the age of 16years has improved from 50 to 80% in 40years. Assessment of potential for preservation of fertility should thus be a systematic element of care for children treated for a malignant tumor (high-dose chemotherapy with alkylizing agents, radiation therapy including the gonads) or those receiving hematopoietic stem cell grafts for malignant or benign disease (sickle-cell anemia, immune deficit). Among the techniques proposed, cryopreservation of ovarian tissue appears to be the most promising, or perhaps the only one available before puberty with encouraging result. Nevertheless the uncertainties, or even risks, related to these treatments, should not be neglected. PMID- 20362961 TI - Anti-Mullerian hormone (AMH): regulator and marker of ovarian function. AB - In this review, the role of anti-Mullerian hormone (AMH) as a regulator and marker of ovarian function is described. Studies in mice showed that AMH is one of the intra-ovarian growth factors regulating primordial follicle recruitment and follicle-stimulating hormone (FSH) sensitivity of growing follicles in an inhibitory manner. Association studies of common variants of the AMH and AMHRII gene suggest that AMH may have a similar role in the human ovary. When it was discovered that serum levels AMH are correlated with the number of growing follicles, AMH gained further clinical interest as a marker for the quantitative aspect of ovarian reserve and as a diagnostic marker for polycystic ovary syndrome (PCOS). PMID- 20362962 TI - Clinical genetics of Kallmann syndrome. AB - The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease. KAL1, encoding the extracellular glycoprotein anosmin-1, is responsible for the X chromosome-linked recessive form of the disease (KAL1). Mutations in FGFR1 or FGF8, encoding fibroblast growth factor receptor-1 and fibroblast growth factor 8, respectively, underlie an autosomal dominant form with incomplete penetrance (KAL2). Mutations in PROKR2 and PROK2, encoding prokineticin receptor-2 and prokineticin-2, have been found in heterozygous, homozygous, and compound heterozygous states. These two genes are likely to be involved both in autosomal recessive monogenic (KAL3) and digenic/oligogenic KS transmission modes. Mutations in any of the above-mentioned KS genes have been found in less than 30% of the KS patients, which indicates that other genes involved in the disease remain to be discovered. Notably, KS may also be part of pleiotropic developmental diseases including CHARGE syndrome; this disease results in most cases from neomutations in CHD7 that encodes a chromodomain helicase DNA-binding protein. PMID- 20362963 TI - Genome-wide association study and premature ovarian failure. AB - Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future. PMID- 20362964 TI - What have we learned form monogenic forms of severe insulin resistance associated with PCOS/HAIRAN? AB - Whatever the origin of severe insulin resistance (primary insulin receptors defects or lipodystrophies), in vivo hyperinsulinemia has been clearly shown to promote ovarian growth and androgen synthesis independently of gonadotropins. In lipodystrophic syndromes, the endocrine deficiency of adipose tissue has been shown to play important pathophysiological roles in metabolic alterations. In particular leptin is decreased, contributing to the ectopic lipid storage in non adipose cells, which inhibits insulin signalling (lipotoxicity). Finally, polycystic ovary syndrome (PCOS) features are not always present in insulin resistance syndromes with lipodystrophy. This is in favour of an aggravating, but not a primary role of post-receptor insulin resistance on ovary dysfunctions. PMID- 20362965 TI - Hypothalamic amenorrhea: from diagnosis to therapeutical approach. AB - Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies. PMID- 20362966 TI - Ovarian hyperstimulation syndrome (OHSS) due to mutations in the follicle stimulating hormone receptor. AB - Ovarian hyperstimulation syndrome (OHSS) is usually a complication of assisted reproductive techniques, more rarely an affection complicating a spontaneous gestation. The cause of hyper responsiveness of ovaries to the gonadotropins used in the controlled stimulation is still largely unknown. In contrast, a few cases of spontaneous hyperstimulation syndrome have been elucidated by the identification of mutations of the follicle-stimulating hormone (FSH) receptor, broadening its specificity and making it hypersensitive to human chorionic gonadotropin (hCG). Surprisingly, the mutations were located in the transmembrane domain of the receptor rather than in the extracellular hormone-binding site. No such mutation has been found in iatrogenic cases. However, allelic variants of the FSH receptors have been associated with the response to FSH in stimulation procedures, as well as with the severity of OHSS when present. PMID- 20362968 TI - Epigenetics, genomic imprinting and assisted reproductive technology. AB - Epigenetic mechanisms play a key role in regulating gene expression. One hallmark of these modifications is DNA methylation at cytosine residues of CpG dinucleotides in gene promoters, transposons and imprinting control regions. Genomic imprinting refers to an epigenetic marking of genes that results in monoallelic expression depending on their parental origin. There are two critical time periods in epigenetic reprogramming: gametogenesis and early preimplantation development. Major reprogramming takes place in primordial germ cells in which parental imprints are erased and totipotency is restored [1]. Imprint marks are then and re-established during spermatogenesis or oogenesis, depending on sex [1 3]. Upon fertilization, genome-wide demethylation occurs followed by a wave of de novo methylation, both of which are resisted by imprinted loci [4]. Epigenetic patterns are usually faithfully maintained during development. However, this maintenance sometimes fails, resulting in the disturbance of epigenetic patterns and human disorders. For example, two fetal growth disorders, the Beckwith Wiedemann (BWS) and the Silver-Russell (SRS) syndromes with opposite phenotypes, are caused by abnormal DNA methylation at the 11p15 imprinted locus [5-7]: respectively loss of methylation at the Imprinting Region Center (ICR2) or gain of methylation at ICR1 in BWS and loss of methylation at ICR1 in SRS. Early embryogenesis is a critical time for epigenetic regulation, and this process is sensitive to environmental factors. The use of assisted reproductive technology (ART) has been shown to induce epigenetic alterations and to affect fetal growth and development [8-11]. In humans, several imprinting disorders, including BWS, occur at significantly higher frequencies in children conceived with the use of ART than in children conceived spontaneously [12,13]. The cause of these epigenetic imprinting disorders (following ART, unfertility causes, hormonal hyperstimulation, in vitro fertilization-IVF, Intracytoplasmic sperm injection ICSI, micro-manipulation of gametes, exposure to culture medium, in vitro ovocyte maturation, time of transfer) remains unclear. However, recent data have shown that in patients with BWS or SRS, including those born following the use of ART, the DNA methylation defect involves imprinted loci other than 11p15 [14,15] (11p15 region: CTCF binding sites at ICR1, H19 and IGF2 DMRs, KCNQ1OT1 [ICR2], SNRPN [chromosome 15 q11-13], PEG/MEST1 [chromosome 7q31], IGF type2 receptor and ZAC1 [chromosome 6q26 et 6q24 respectively], DLK1/GTL2-IG-DMR [chromosome 14q32] and GNAS locus [chromosome 20q13.3]). This suggests that unfaithful maintenance of DNA methylation marks following fertilization involves the dysregulation of a trans-acting regulatory factor that could be altered by ART. PMID- 20362967 TI - Oocyte-somatic cell communication and microRNA function in the ovary. AB - An enormous amount of knowledge about the ovary has been generated over the last two decades, due in part to the development of strategies to genetically manipulate the mouse using embryonic stem cell technology. Our group and others have identified multiple factors that are important and essential at all stages of ovarian folliculogenesis from formation of the primordial factor to ovulation. It is obvious that an oocyte, the key cargo of the ovary, and the surrounding granulosa cells, the support cells of the follicle, entertain a dialog that is key for granulosa growth and differentiation and oocyte growth, maturation, and fertilization. In addition to the involvement of genes in these processes, small non-coding RNAs including microRNAs and siRNAs have been implicated as key regulators, especially in the oocyte. These studies have direct implications for human fertility control in the assisted reproductive technology (ART) laboratory. PMID- 20362969 TI - Aberrant follicle development and anovulation in polycystic ovary syndrome. AB - Endocrine factors appear to play an important part in arrest of antral follicle maturation in polycystic ovary syndrome (PCOS) but are unlikely to have an impact on early, preantral follicle development, which is clearly abnormal in PCOS. Disordered early folliculogenesis in PCOS is characterised by a higher proportion of follicles entering the growing phase and more prolonged survival of small follicles than in normal ovarian tissue. The factors responsible for aberrant preantral follicle development remain to be determined but IGFs, growth factors of the TGFbeta family and androgens may all have a role. PMID- 20362970 TI - Consequences of genetic manipulations of gonadotrophins and gonadotrophin receptors in mice. AB - We have produced over the years several genetically modified mouse models (transgenic [TG], knockout [KO] and knockin [KI]) for the study of normal and aberrant functions of gonadotrophins and their receptors. We summarise in the present review some of our recent findings on these animal models. One is the cascade of extragonadal phenotypes triggered by ovarian hyperstimulation in TG mice overexpressing the human choriongonadotrophin (hCG) beta-subunit and presenting with elevated levels of serum luteinising hormone (LH)/hCG bioactivity. Massively elevated levels of serum progesterone, rather than oestrogens, are responsible for the induction of pituitary prolactinomas and the subsequently elevated prolactin (PRL) levels. Along with normal oestradiol and elevated progesterone levels, the increased concentration of PRL induces lobuloalveolar development of the mammary gland, with ultimate formation of oestrogen and progesterone receptor-negative malignant tumours. Another TG mouse model expressing a constitutively activating mutant form of the follicle stimulating hormone receptor (FSHR) presents with a strong ovarian phenotype inducing advanced follicular development and depletion, haemorrhagic follicles, teratomas and infertility. A third TG mouse model, coexpressing binding- and signalling-deficient mutants of LHCGR in the KO background for the same receptor (R) gene provided convincing evidence that functional complementation through homo-di/oligomerisation is a physiologically relevant mode of activation of class A G protein-coupled receptors (GPCR). Taken together, genetically modified mouse models provide powerful tools for the elucidation of normal and pathological functions of gonadotrophins and their R. PMID- 20362971 TI - [Phenotype-genotype correlation in mutations of the gonadotrophin receptor gene in women]. AB - Different mutations have been described in LH and FSH genes as well as in their receptors. These mutations are either activating (gain of function), or inhibiting (loss of function). Activating mutations are expressed as a dominant trait, thus in the heterozygous state, whereas inhibiting mutations are only expressed when both alleles bear the mutation. Inactivating mutations of FSH receptor gene, in women, are associated with primary ovarian insufficiency. Inactivating mutations of LH receptor gene have also been described, most often in XX patients whose families also include cases of male pseudohermaphrodism. Clinically, these women suffer from primary amenorrhea but with normal development of breasts and the hair system. Infertility is constant. LH blood levels are increased, estradiol blood levels are those encountered at the beginning of the follicular phase (50-70 pg/ml). The discovery of these mutations allows a better understanding of some genotypes and is helpful in advancing our knowledge of these receptors. PMID- 20362972 TI - Ovarian dysfunction by activating mutation of GS alpha: McCune-Albright syndrome as a model. AB - The McCune-Albright syndrome is characterized by cafe-au-lait spots, precocious puberty, and fibrous dysplasia. It is due to mutations in the gene encoding the GS protein alpha subunit coupling 7-transmembrane-domain receptors to adenylate cyclase, leading to constitutive adenylate cyclase activation and cAMP overproduction. Endocrinologists and gynecologists are confronted with new issues when these children reach adulthood. Gonadal function and fertility are often abnormal in women in whom puberty was precocious, owing to the persistence of a variable degree of ovarian autonomy that hinders adequate follicular development and ovulation. PMID- 20362973 TI - Human ovarian follicular development: from activation of resting follicles to preovulatory maturation. AB - By integrating morphometrical and endocrinological data, as well as biological effects of various molecules synthesized by the human follicle, we propose a dynamic view of the follicle growth within the human ovary. Folliculogenesis starts with entry of resting follicles into the growth phase, a process where the kit system plays a key role. Several months are required for a new growing follicle to reach the preantral stage (0.15mm), then 70 additional days to reach the size of 2mm. Early growing follicle growth is regulated by subtle interactions between follicle-stimulating hormone (FSH) and local factors produced by theca and granulosa cells (GCs), as well as the oocyte. From the time they enter the selectable stage during the late luteal phase, follicles become sensitive to cyclic changes of FSH in terms of granulosa cell proliferation. During the early follicular phase, the early selected follicle grows very quickly and estradiol is present in the follicular fluid. However, the total steroid production remains moderate. From the mid-follicular phase, the preovulatory follicle synthesizes high quantities of estradiol, then after the mid-cycle gonadotropin surge, very large amounts of progesterone. At this stage of development, the responsiveness of the follicle to gonadotropins is maximum, especially to luteinizing hormone (LH) that triggers granulosa wall dissociation and cumulus expansion as well as oocyte nuclear maturation. Thus, as the follicle develops, its responsiveness to gonadotropins progressively increases under the control of local factors acting in an autocrine/paracrine fashion. PMID- 20362974 TI - Kisspeptins and the metabolic control of reproduction: physiologic roles and physiopathological implications. AB - In this presentation, we have provided a succinct state-of-the-art of our knowledge on kisspeptins, the newly identified neuropeptide system with key roles in the control of the gonadotropic axis, in the metabolic regulation of puberty onset and fertility. The experimental evidence revised herein, gathered mostly in rodent models, supports the contention that hypothalamic Kiss1 neurons do operate as a central conduit for conveying metabolic information onto the centers governing reproductive function, through a putative leptin-kisspeptin-GnRH pathway, which is likely to involve Crtc1 and/or mTOR as molecular mediators. PMID- 20362975 TI - Need for speed: evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine. AB - Evidence suggests that the antibiotic d-cycloserine (DCS) enhances the treatment effects of exposure and response prevention (ERP) for Obsessive-Compulsive Disorder (OCD). Further, evidence suggests that the effects of DCS diminish partway through treatment, but it is unclear to what extent. In an effort to evaluate these issues, the current study re-analyzes data from a 10-session randomized controlled trial of ERP+DCS versus ERP+placebo in a sample of 22 adults with OCD. We analyzed repeated-measures mixed models with random slopes and intercepts across different intervals: sessions 1-10, 1-5, and 6-10. The results indicate that the course of ERP was 2.3 times faster over the full 10 sessions for the DCS compared to the placebo group, and nearly six times quicker in the first half of ERP. Further interpretation of the results suggests that DCS does not amplify the effects of ERP, but instead initiates treatment effects sooner in treatment. In addition, DCS does not necessarily lose its effect over repeated use, but instead may exhaust its maximum utility after effectively jump starting ERP. Ultimately, DCS may provide a means for curtailing treatment costs, decreasing treatment dropout and refusal rates, and enhancing access to care. PMID- 20362976 TI - Internet-delivered exposure and mindfulness based therapy for irritable bowel syndrome--a randomized controlled trial. AB - The aim of this study was to investigate if cognitive behavior therapy (CBT) based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome (IBS). Participants were recruited through self-referral. Eighty-six participants were included in the study and randomized to treatment or control condition (an online discussion forum). One participant was excluded after randomization. The main outcome measure was IBS-symptom severity and secondary measures included IBS related quality of life, GI-specific anxiety, depression and general functioning. Participants were assessed at pre-treatment, post-treatment and 3 month follow-up (treatment condition only). Four participants (5% of total sample) in the treatment condition did not participate in post-treatment assessment. Participants in the treatment condition reported a 42% decrease and participants in the control group reported a 12% increase in primary IBS-symptoms. Compared to the control condition, participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life (Cohen's d = 1.21). We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS-patients, alleviating the total burden of symptoms and increasing quality of life. PMID- 20362977 TI - Distinguishing rumination from worry in clinical insomnia. AB - Research has found that repetitive thought processes, such as worry and rumination, play an important role in several disorders; however, these cognitive processes have not yet been examined in insomnia. This study explores rumination and worry in insomnia by examining: 1) whether those high and low on rumination and worry differ on subjective sleep measures, and 2) whether rumination and worry are distinct processes in insomnia. Participants (N=242) were diagnosed with an insomnia disorder by sleep experts. Participants completed measures of worry and rumination and maintained a 2-week daily sleep log. Results of a multivariate analysis of variance found no main effect of worry; although high and low ruminators differed on several sleep log indices, including sleep efficiency, wakefulness after sleep onset and sleep quality. Factor analysis supported the idea that rumination and worry are separate constructs. Whereas previous research has focused on worry in insomnia, these findings suggest that rumination is important for understanding sleep disturbance. Further, although rumination and worry are both repetitive thought processes, these results indicate that they are distinct processes within insomnia and should be treated as such. The results are discussed with respect to treatment implications for Cognitive Behavioural Therapy for Insomnia. PMID- 20362979 TI - How children use examples to make conditional predictions. AB - Two experiments explored children's and adults' use of examples to make conditional predictions. In Experiment 1 adults (N=20) but not 4-year-olds (N=21) or 8-year-olds (N=18) distinguished predictable from un-predictable features when features were partially correlated (e.g., necessary but not sufficient). Children did make reliable predictions given perfect correlation. In the context of categorization and property projection in Experiment 2, children of both ages (both N=31) and adults (N=30) did use partial correlation in examples to make conditional predictions. However, predictions of category membership given property possession were more reliable than were predictions of property possession given category membership. Children generally showed good memory for frequency information, but did not always use this information as the basis of predictions. Results suggest that young children may have difficulty selectively using the relations they observe in experience. PMID- 20362978 TI - The process of change in cognitive therapy for depression: predictors of early inter-session symptom gains. AB - Although cognitive therapy for depression is an efficacious treatment, questions about the aspects of the therapy that are most critical to successful implementation remain. In a sample of 60 cognitive therapy patients with moderate to severe depression, we examined three aspects of therapists' adherence to cognitive therapy techniques, the patients' facilitation or inhibition of these techniques, and the therapeutic alliance as predictors of session-to-session symptom improvement across the first five therapy sessions. Two elements of therapist adherence (viz., cognitive methods and negotiating content/structuring sessions) emerged as the strongest predictors of symptom improvement. Patient facilitation or inhibition of therapist adherence also predicted subsequent symptom change. Neither adherence to behavioral methods/homework nor the therapeutic alliance was a significant predictor in parallel analyses. Although alliance scores did not predict subsequent symptom change, they were significantly predicted by prior symptom change. These findings support the model of change that motivates cognitive therapy for depression, and they highlight the potential role of patient facilitation of therapists' adherence in treatment response. PMID- 20362980 TI - Quantitative and mid-infrared changes of humic substances from burned soils. AB - The humic substances are an abundant and important part of soil organic matter which plays many roles in ecosystems. On the other hand, forest fires are known to have a potential impact on the soil organic matter. Consequently, we chose to study the impact of forest fires on humic substances and the three relevant fractions, e.g. humic acids (HA), fulvic acids (FA) and non-humified fraction (NHF), NHF being the fulvic acids not adsorbed on XAD-8 resins. The studied site is a Mediterranean forest called "Maures Mountains", in France, where 30 sites were sampled in two layers: 0-5 and -5 to 15 cm. In order to validate the method, the 2 horizons from 5 sites randomly chosen were analyzed in triplicates. The extraction and fractionation procedures were achieved using alkali- and acid solutions. The measurement of total organic carbon (TOC) using the TOC-meter and the use of Fourier transform infra-red (FTIR) spectroscopy gave us quantitative and qualitative results to evaluate the impact of forest fires and the role of their repetition. The results show that the fires led to significant decreases (Student test, P=0.05) of humic substances (HS), HA and of the fulvic fractions (FF=FA+NHF) in surface layers, corresponding to 40%, 34% and 35%, respectively. Moreover, the significant HA/FF ratio increases (Student test, P=0.05), as a result of the fire, indicate that NHF was probably transformed in FA-like compounds. About the qualitative impact, the results showed a significant decrease of alkyl and hydroxyl groups (OH), carboxylic acids and carbohydrates in HA after a wildfire, whereas the decrease was significant only for alkyl groups and carboxylic acids in FA. Lastly, the design of this work (control and burned sites, number of samples, time elapsed after fires, etc.) enables one to show the recovery of the Mediterranean forest ecosystem. FA quality and OH groups in HA are recovered between 3 and 16 years after the fire whereas alkyl groups, carboxylic acids and carbohydrates in HA as well as HS contents are not returned to the control state 16 years after the last fire. PMID- 20362981 TI - The epidemiology of BCVI at a single state trauma centre. AB - BACKGROUND: Blunt carotid and vertebral artery injury (BCVI) is a relatively uncommon but potentially devastating injury. The aim of our study was to highlight the incidence, patterns, presentation and associations of BCVI at our institution. METHODS: Retrospective data between 1st January 2003 and 31st December 2006 was obtained from The Alfred Hospital's health information system, patient medical records and the Department of Neurosurgery's database. Injuries were graded using the Denver grading scale. RESULTS: 67 patients (0.64%) out of 10,417 minor and major trauma admissions, were diagnosed with BCVI. 33 (49%) sustained blunt carotid and 34 (51%) sustained blunt vertebral injuries. Motor vehicle accident (MVA) was the cause in 43 out of 67. 35% had associated head injury whilst 57% had concurrent cervical spine fractures. Odds ratio analysis showed that MVA victims with concomitant upper cervical spine injury were 22.9 times more likely to suffer BCVI than those without such risk factors. Approximately 50% of patients had a Glasgow coma score of 14 or less (GCS < or = 14). Grade 4 BCVI was most common. Stroke occurred in 22 (32%) and mortality in 14 (20%). CONCLUSION: BCVI although infrequent, is a serious injury. Our study suggests that MVA patients with cervical spine fractures especially of the upper C-spine are at much higher risk of BCVI than those without such injuries. PMID- 20362982 TI - Topical negative pressure and military wounds--a review of the evidence. AB - BACKGROUND: Topical negative pressure (TNP) has been used as a method of wound management for some years. Use of TNP is accepted best practice at Role 4. There are advocates of using TNP after initial wound surgery at Role 3 or 2E. The evidence to support forward use of TNP is not comprehensive, especially when considering this narrow cohort of patients and injury pattern. It is the aim of this review to evaluate the current evidence for the use of TNP in all wounds, and to find what evidence there is that may be applicable to military wounds. METHODS: A literature search of Cinahl, Embase, Medline, ProQuest and the Cochrane Library was conducted; references were cross-referenced. All Randomised Controlled Trials (RCTs) were included in all languages over a comprehensive time period. An interim review was conducted by the Wound Management Working Group of the Academic Department of Military Surgery and Trauma. A further literature review was conducted to find all papers relating to the use of TNP on military wounds. RESULTS: 17 reports were reviewed relating to 14 studies including 662 patients. Of these 131 were reported to have had traumatic injuries. Significant results were reported with respect to time to wound healing, patient comfort and reduction in wound volumes. Bacterial load was not affected, in the 3 trials which commented on this, but in 1 there was a significant reduction in wound infections in the TNP group. Several of the trials were small, methodology was not consistent therefore no meta-analysis was possible. 2 papers were found describing case series of military patients being treated with TNP. CONCLUSIONS: There is very little published evidence in the form of RCTs to support the use of TNP in the acute traumatic military setting. This review supports the requirement for further investigation to evaluate whether this method of wound management has a place forward of Role 4. PMID- 20362983 TI - The changing face of mild head injury: temporal trends and patterns in adolescents and adults from 1997 to 2008. AB - OBJECTIVE: To explore the temporal trend of incidence, causes of injury and main characteristics of adolescent and adult subjects with mild head injury (MHI). DESIGN: This study had a retrospective design. SETTING: The study was conducted in a longitudinal database of an Italian Emergency Department (ED). PARTICIPANTS: The study comprised 19124 consecutive subjects who visited and were managed within 24 h from the event, according to a predefined protocol for MHI from 1997 to 2008. MAIN OUTCOME MEASURES: Incidence, demography, cause of injury and characteristics of any post-traumatic intracranial lesion within 7 days from MHI. RESULTS: The number of subjects with MHI decreased from 2019 per year (1997-1999) to 1232 per year (2006-2008; P for linear trend <0.001), without differences in the total number of subjects visited in the ED. The decrease was observed in all age-decades, in particular, in subjects in the age ranges of 20-29 and 30-39 years. Over time, the age of subjects with MHI lost a bimodal distribution, and the mean age increased from 43 (25-69) years (median (interquartile range)) in 1997-1999 to 56 (33-78) years in 2006-2008 (P<0.001). The prevalence of falls increased from 36.5% to 55.0%, whereas crashes fell from 53.2% to 31.9%. The incidence of subdural haematoma (SDH) and epidural haematoma (EDH) did not change over time, whereas traumatic subarachnoid haemorrhage (t-SAH) and intra-cerebral haematoma/brain contusion (ICH) increased (from 0.7% to 1.9% and from 2.5% to 3.2%; P for trend: <0.001 for both. CONCLUSIONS: The incidence and the clinical characteristics of MHI subjects are rapidly changing in our setting. These data need to be considered in defining the effectiveness of preventive measures and deciding resource allocation. PMID- 20362985 TI - Relationship between cardiovascular function and fetal growth restriction in women with pre-eclampsia. AB - OBJECTIVE: To investigate the relationship between cardiovascular function in women with pre-eclampsia and fetal growth restriction (FGR) using impedance cardiography. METHOD: This retrospective study was performed with 639 participants allocated to one of 4 groups, a pre-eclampsia (PE) with FGR group, a PE without FGR group, a pregnancy-induced hypertension (PIH) without FGR group, and normal pregnancy (NP) group. Hemodynamic monitoring was performed noninvasively using impedance cardiography. RESULTS: Mean arterial pressure and peripheral resistance were significantly higher, and cardiac output and maternal systolic function were significantly lower, in the 2 PE groups than in the PIH and NP groups, and these differences were the greatest between the NP and the PE with FGR groups. CONCLUSION: Impedance cardiography allowed to observe a gradual increase in peripheral resistance and cardiac output from the NP group to the PIH, the PE without FGR, and the PE with FGR groups. The most reduced systolic function and cardiac output and the most increased peripheral resistance was observed in the PE with FGR group. PMID- 20362986 TI - Evaluation of cervical screening results in a population at normal risk. AB - OBJECTIVE: To evaluate the frequency of dysplasia and other cervical conditions in a population at normal risk, and compare demographic characteristics of the women with normal and abnormal results. METHODS: Characteristics such as gravidity, parity, age at marriage, and smoking status were obtained from a questionnaire completed from January 2004 through July 2005 at Denizli State Hospital, Denizli, Turkey, by the 19639 participants before they were screened. The results were analyzed. RESULTS: The dysplasias detected in 107 smears (0.54%) included ASCUS (0.31%), LSIL (0.15%), and HSIL (0.07%); there were also 1 case of AGUS and 1 of squamous cell carcinoma. Age, age at marriage, number of pregnancies, number of deliveries, and smoking habit were similar for participants with and without dysplasia (P>0.05). Bacterial vaginosis was seen in 1633 smears (8.3%), candidiasis in 1346 (6.9%), Actinomyces sp. in 648 (3.3%), and Trichomonas vaginalis in 143 (0.7%). CONCLUSION: Cytologic abnormalities in a cervical smear can point to precancerous or cancerous processes or to other conditions. The prevalence of dysplasia was lower for our participants than in Western populations, which could be explained by a conservative lifestyle and a lower prevalence of HPV in Turkey. PMID- 20362987 TI - Abdominal papular zosteriform cutaneous metastases from endometrial adenocarcinoma. PMID- 20362988 TI - Treatment of intravenous leiomyoma with transcatheter arterial embolization. PMID- 20362989 TI - Midtrimester abortion using vaginal misoprostol for women with three or more prior cesarean deliveries. AB - OBJECTIVE: To evaluate the safety and efficacy of vaginal misoprostol for second trimester abortion in women with 3 or more prior cesarean deliveries. METHODS: This study was conducted with 138 women who needed pregnancy termination between 13 and 26 gestational weeks, 31 with 3 or more previous cesarean deliveries and 107 with no uterine scars (the controls). Misoprostol was inserted in the vagina every 6 hours until regular contractions or products of conception appeared, a 200-microg tablet for the first 24 hours and 2 tablets thereafter. The outcomes assessed were successful vaginal abortion, hemorrhage requiring blood transfusion, incomplete abortion, and uterine rupture. RESULTS: A vaginal abortion occurred in 28 women (90.3%) in the study group and 107 (100%) in the control group (P=0.01). There were no significant differences in the prevalence of the other assessed outcomes. CONCLUSION: Vaginal misoprostol appears to be safe and acceptably effective for second-trimester pregnancy termination in women with 3 or more previous cesarean deliveries. PMID- 20362990 TI - Challenges associated with hypertensive disease during pregnancy in low-income countries. AB - OBJECTIVE: To assess the challenges associated with the diagnosis, management, and prevention of hypertensive disease during pregnancy in low-income countries, following the success of the Magpie Trial. METHODS: Descriptive review of the literature from 1990 to 2009 on the diagnosis, management, and prevention of hypertensive disease in pregnancy. RESULTS: In the absence of credible measures to predict and prevent hypertension in pregnancy, diagnosis and treatment remain the only viable options, although they are still associated with important challenges in low-income countries. Despite the presence of high-quality evidence that magnesium sulfate is safe and effective at preventing and treating eclampsia, its use is extremely limited in many low-income countries. CONCLUSION: There is a need for cheap and reliable tools with which to address the diagnostic, preventive, and management challenges associated with hypertensive disease during pregnancy in low-income countries. It is recommended that such countries incorporate magnesium sulfate protocols into their national health and/or practice policies. PMID- 20362991 TI - Factors associated with failure to achieve birth emphasizing a successful singleton at term following in vitro fertilization. AB - OBJECTIVE: To evaluate the factors that might affect birth emphasizing a successful singleton at term (BESST) outcomes in women undergoing in vitro fertilization. METHODS: A retrospective review of assisted reproduction cases from January 1, 2001, to July 31, 2005, at the Far Eastern Memorial Hospital, Taipei, Taiwan. Variables that were potentially associated with failure to achieve BESST were evaluated using univariate and multivariate logistic regression analysis. RESULTS: Successful embryo transfer occurred in 297 of the 323 cases of assisted reproduction. In total, 123 women became pregnant and were enrolled for analysis, of whom 94 had live births and 55 achieved BESST. Multivariate analysis indicated that the number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors (other than tubal factors), and embryo quality were associated with increased relative risk of BESST failure, with odds ratios of 1.02 (95% confidence interval [CI], 1.01-1.02), 1.21 (95% CI, 1.08-1.36), 1.41 (95% CI, 1.22-1.62), and 0.79 (95% CI, 0.68-0.91), respectively. CONCLUSION: The number of embryos transferred, the presence of ovarian hyperstimulation syndrome, female infertility factors other than tubal factors, and embryo quality correlate with the risk of failure to achieve BESST. PMID- 20362992 TI - Evaluation of an interpersonal-psychotherapy-oriented childbirth education programme for Chinese first-time childbearing women: a randomised controlled trial. AB - OBJECTIVE: This study investigated the effects of an interpersonal-psychotherapy oriented childbirth psychoeducation programme on postnatal depression, psychological well-being and satisfaction with interpersonal relationships in Chinese first-time childbearing women. METHOD: A randomised, controlled trial was conducted in the maternity clinic of a regional hospital in China. The intervention was based on the principles of interpersonal psychotherapy, and consisted of two 90-min antenatal classes and a telephone follow-up within 2 weeks after delivery. One hundred and ninety-four first-time pregnant women were randomly assigned to the intervention group (n=96) or a control group (n=98). Outcomes of the study included symptoms of postnatal depression, psychological well-being and satisfaction with interpersonal relationships, which were measured by the Edinburgh Postnatal Depression Scale (EPDS), General Health Questionnaire (GHQ) and Satisfaction with Interpersonal Relationships Scale (SWIRS), respectively. RESULTS: Women receiving the childbirth psychoeducation programme had significantly better psychological well-being (t=-3.33, p=0.001), fewer depressive symptoms (t=-3.76, p=0.000) and better interpersonal relationships (t=3.25, p=0.001) at 6 weeks postpartum as compared with those who received only routine childbirth education. CONCLUSION: An interpersonal-psychotherapy-oriented childbirth psychoeducation programme could be implemented as routine childbirth education with ongoing evaluation. Replication of this study with more diverse study groups, such as mothers with high risks to depression, those with multiple, complicated or multiparas pregnancies, would provide further information about the effects of the programme. PMID- 20362993 TI - Association between metabolic syndrome or its components and asymptomatic cardiovascular disease in the RIVANA-study. AB - OBJECTIVE: To assess the association between the metabolic syndrome (MetSd) and asymptomatic cardiovascular disease and determine if the MetSd or its single risk factors perform better in discriminating prevalent asymptomatic cardiovascular disease. METHODS: A total of 880 community-dwelling subjects (423 with and 457 without MetSd according to ATPIII) underwent a physical examination, an echocardiography and an ultrasound examination of carotid arteries and blood and urine samples were collected. Associations between the subclinical organ damage markers and the MetSd were addressed with non-conditional logistic regression. AUCs of ROCs were used to compare the models' ability to discriminate asymptomatic cardiovascular disease. RESULTS: The MetSd was independently associated with carotid subclinical atherosclerosis, increased left ventricular mass index and cardiac dysfunction. The MetSd did not discriminate prevalent increased carotid intima-media thickness better than abdominal obesity and impaired fasting glucose [AUC=0.75 (95% CI: 0.71-0.78) and 0.75 (0.71-0.79), respectively; p=0.55]. The MetSd performed worse than abdominal obesity in discriminating increased left ventricular mass index among males younger than 65 years [AUC=0.66 (95% CI: 0.62-0.69) and 0.69 (0.66-0.73), respectively; p=0.02]. No differences between the ability of MetSd or its components in discriminating increased left ventricular mass index were observed among older men or women. The discrimination ability for microalbuminuria for the MetSd or impaired fasting glucose was not statistically different [AUC=0.67 (95% CI: 0.60-0.74) and 0.69 (0.62-0.76), respectively; p=0.18]. CONCLUSION: This study supports the association between the MetSd and asymptomatic cardiovascular disease. The construct of the MetSd might not be better than its single components in addressing cardiovascular risk. PMID- 20362994 TI - Study of the selectivity, retention mechanisms and performance of alternative silica-based stationary phases for separation of ionised solutes in hydrophilic interaction chromatography. AB - The separation of a mixture of neutral, strongly acidic and strongly basic compounds was studied in hydrophilic interaction chromatography using a bare silica phase, and bonded silica phases with diol, zwitterionic, amide and hydrophilic/hydrophobic groups. The mobile phase was acetonitrile-ammonium formate buffer at low pH. Differences in selectivity between these various columns indicate that the stationary phase cannot function merely as an inert support for a water layer into which the solutes partition from the bulk mobile phase. Attempts to fit the retention data to equations which describe either partition or adsorption mechanisms were inconclusive. Ion exchange was a significant contributor to the retention of ionised bases on all columns studied. Van Deemter plots indicated that the efficiency as a function of flow rate varied between the columns, which might be attributable in part to the presence of either monomeric or polymeric bonded phase layers. PMID- 20362995 TI - Size and density dependent sedimentation analysis of advanced nanoparticle systems. AB - Various functional colloidal systems like polymer grafted inorganic particles, complex multi-component mixtures, organic-inorganic hybrid particles, inorganic inorganic core-shell particles and swellable particles were characterized by sedimentation coefficient analysis in analytical ultracentrifuge owing to the accurate correlation of the sedimentation coefficient with variations in size and density of the materials. The sedimentation coefficient is absolute in nature and does not require any property information beforehand. By following the changes in the sedimentation coefficient and its distribution, it could be established if the polymer grafting on the surface of the inorganic particles took place or if the organic-inorganic or inorganic-inorganic hybrid was formed or if the particles were strongly crosslinked or swellable. The complex particle mixtures were also quantified for the number of components contained in them and their exact amounts by following the sedimentation coefficient distributions. PMID- 20362996 TI - A method to determine zeta potential and Navier slip coefficient of microchannels. AB - The no-slip boundary condition for liquid flows in microchannel has been applied successfully although it has no theoretical foundation. Liquid molecules, however, can slip at the liquid-solid interfaces if the liquid has a lower wettability. The velocity slip at the solid wall, called the Navier slip, is proportional to the velocity gradient at the wall for given wall physicochemical properties. Since the electroosmotic flow has a sharp velocity variation at the wall, the Navier slip of electroosmotic flow can be appreciable in a microchannel where there may be negligible Navier slip for a purely pressure-driven flow which has a smoother velocity variation at the wall. The Navier slip affects the volumetric flow rate and streaming potential significantly in electrokinetic flows and, therefore, one must be cautious about the possible occurrence of Navier slip in the design and operation of various microfluidic devices. In the present work, we have devised a simple method of estimating both Navier slip coefficient and zeta potential by measuring both the volumetric flow rate under a given pressure gradient after eliminating streaming potential and streaming potential under a given pressure gradient. Instead of streaming potential, one may adopt volumetric flow rate under a given external electric field. The method relies on a semi-analytic formula derived in the present work, which allows evaluation of streaming potential and volumetric flow rate without the necessity of numerical solution of nonlinear partial differential equations. The present method is found to estimate both slip coefficient and zeta potential reasonably accurately even using contaminated experimental data. PMID- 20362997 TI - Self-modulating polymer resist patterns in pressure-assisted capillary force lithography. AB - We present pressure-assisted capillary force lithography (CFL) to generate self modulating polymer resist patterns without residual layers and film instability. The method utilizes roof collapse of a patterned, deformable poly(dimethyl siloxane) (PDMS) mold that is placed on a thermoplastic polymer film with a constant external pressure (approximately 4 bars) and the resulting shape variable capillary filling of a polymer melt into the reduced void space. A constraint on the coated polymer layer thickness was derived in order to ensure that there is no residual layer left after patterning and at the same time that film stability is guaranteed without film dewetting within the cavity. In addition, the height of a polymer pattern at the center of the filled void was estimated as a function of initial polymer layer thickness based on the assumption of the hemispherical shape of a meniscus and full capillary rise, which agrees well with the experimental data. PMID- 20362998 TI - Determination of the wettability of powders by the Washburn capillary rise method with bed preparation by a centrifugal packing technique. AB - The Washburn capillary rise method is a standard technique for determining the wettability of powders expressed as a contact angle. The method requires the preparation of two identical beds of powder. One of these beds is used to follow the capillary rise with a perfectly wetting liquid (contact angle = 0) giving access to a bed structure parameter. The other bed is used with the liquid of interest (contact angle not = 0) and the capillary rise data is analysed using the previously determined structure parameter to obtain the contact angle. In the experiments reported here we have used a centrifugal packing technique to prepare beds of powder. This gives reproducible packings and also allows a certain degree of control of the bed porosity. In addition the air permeability of the beds is also determined prior to the capillary rise experiments. The results show that the value of the contact angle of a powder determined by the Washburn method depends on the porosity of the powder bed, and that the structure parameter can be determined from the air permeability using the Kozeny-Carman expression. PMID- 20362999 TI - Organoclay particles as reinforcing agents in polysaccharide films. AB - In this work an investigation is described on the use of organically modified montmorillonite clay particles as stabilizers of bioplastic films based on xylan. With the aim of facilitating the incorporation of the nanoparticles to the films, the former were treated with a non-ionic surfactant, inulin. In order to evaluate the possible role of electrostatic interactions in the formation of montmorillonite/xylan complexes, an exhaustive electrokinetic characterization of the modified montmorillonite was carried out. Because montmorillonite has been modified by adsorption of the cationic surfactant DSDMAC, the electrophoretic mobility of montmorillonite in the absence of inulin is positive in a wide range of concentration of NaCl and CaCl(2). On the contrary, addition of KBr provokes a charge inversion when the salt concentration is around 0.05 M, suggesting adsorption of Br(-) ions. In the presence of inulin, the positive electrophoretic mobility decreases with the concentration of this surfactant, and this can be explained by assuming that inulin adsorption is accompanied by simultaneous DSDMAC desorption, eventually producing charge inversion, particularly in the presence of bromide ions. A thorough characterization of the wettability of the xylan films demonstrated that it is dominated by acid-base interactions and that incorporation of inulin-coated montmorillonite leads to a considerable reduction of the hydrophilic character of the films. PMID- 20363000 TI - Intracranial embolism characteristics in PFO patients: a comparison between positive and negative PFO by transesophageal echocardiography: the rule of nine. AB - BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) can be diagnosed by contrast enhanced transcranial Doppler (cTCD), but no definitive criteria exist to correlate the results obtained from cTCD with diagnoses of PFO obtained by contrast-enhanced transesophageal echocardiography (cTEE). The aim of the present study was to analyze markers in the positive RLS by cTCD that confirm the PFO by cTEE. METHODS: Twenty-six stroke patients who had previously submitted to cTEE, 16 with PFO (PFO group) and 10 without PFO (no-PFO group), were evaluated for three markers based on a positive cTCD test. The number of microembolic signs (MES), the latency time (LT) to the first MES and the duration time (DT) of MES were evaluated to look for a difference between the PFO and no-PFO group. RESULTS: The PFO group had higher MES (80.9+/-124.5 vs. 10.2+/-25.6, p<0.001), shorter LT (12.5+/-6.6 vs. 16.2+/-5.1, p=0.02) and longer DT (21.4+/-17.4 vs. 11.7+/-12.5, p=0.013) compared with the no-PFO group. Considering only MCA tests with more than 9 MES and LT shorter than 9s, 30% of patients from the PFO group had positive tests compared with no patients from the no-PFO group. This cutoff demonstrates a specificity and positive predictive value of 100%. CONCLUSIONS: The rule of nine (>9 MES and LT <9s) for cTCD can be considered a marker for PFO diagnosis by cTEE. PMID- 20363001 TI - Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery. AB - OBJECTIVE: We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS: Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS: A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS: An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only. PMID- 20363002 TI - Surgical excision of right ventricular carcinoid tumor in a symptomatic patient without carcinoid valve disease. PMID- 20363003 TI - Left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves: an in vivo study using echocardiographic particle image velocimetry. AB - OBJECTIVE: Echocardiographic particle image velocimetry is a new feature tracking based approach to visualize and quantify left ventricular flow patterns in vivo. We investigated the potential role of this new technique by assessing vortex formations in healthy left ventricles and the effect of different types of prosthetic valves on intraventricular flow patterns and flow-mediated energy dissipation. METHODS: We examined 19 patients (mean age, 57 +/- 19 years; 10 women). Nine were healthy, and 10 had prosthetic mitral valves (5 had bileaflet valves, 4 had bioprostheses, and 1 had a tilting-disc valve). Boluses of left heart contrast were administered intravenously. Echocardiographic apical views were analyzed offline by using prototype software that allowed intracavitary flow to be explored and enabled calculations of energy dissipation (relative pulsatile vorticity strength and vortex pulsation correlation) by means of particle image velocimetry. RESULTS: In healthy hearts a vortex filling the entire ventricle stores the kinetic energy of the blood and smoothly redirects the blood to the outflow tract. In patients with prosthetic valves, completely different flow patterns were identified depending on the type, orientation, and position of the valves, as well as left ventricular geometry. Patients with prosthetic valves showed significantly higher left ventricular energy dissipation than healthy subjects (relative pulsatile vorticity strength, 2.4 +/- 0.7 vs 1.6 +/- 0.4 [P < .001]; vortex pulsation correlation, 1.2 +/- 0.5 vs 0.7 +/- 0.2 [P < .001]). CONCLUSIONS: Echocardiographic particle image velocimetry is feasible. It clearly distinguishes flow patterns in healthy hearts from those in hearts with different types of prosthetic valves. Echocardiographic particle image velocimetry offers new insights into cardiac function and might be of importance to optimize valve replacement therapy. PMID- 20363004 TI - [Tumour necrosis factor alpha antagonists in established rheumatoid arthritis: effectiveness comparative study]. AB - BACKGROUND AND OBJECTIVE: Knowing the differences in the effectiveness between three tumour necrosis factor alpha antagonists (anti-TNF alpha) in rheumatoid arthritis (RA) has important clinical implications. The aim of this study was to assess anti-TNF alpha effectiveness and to study possible differences in outcomes between them. PATIENTS AND METHOD: We included all patients with rheumatoid arthritis (RA) attended in consulting room from Zaragoza Area II between May 2000 and December 2006 who completed a year with anti-TNF alpha treatment. Several demographic and clinical parameters at the beginning and after a year with three different agents were analysed and compared. RESULTS: 119 patients completed a year with anti-TNF alpha, 28 with infliximab, 44 with etanercept and 37 with adalimumab. After a year with treatment, DAS 28 descended 1,82 (1,42) points and HAQ 0,3 (0,58) (p<0,05). Comparing the clinical parameters after a year DAS 28 was 3,8 in the three groups. HAQ was 1,2 for patients in treatment with infliximab and 0,9 for patients with etanercept and adalimumab. There were no significant differences in effectiveness between the 3 drugs. CONCLUSIONS: Anti TNF alpha drugs are effective to treat RA and the effectiveness is similar in all them. PMID- 20363005 TI - Firearm suicide decedents in the Republic of Ireland, 1980-2005. AB - OBJECTIVES: To compare the sociodemographic characteristics of firearms suicide decedents and other suicide decedents in the Republic of Ireland between 1980 and 2005. STUDY DESIGN: A cross-sectional study of sociodemographic characteristics of those who committed suicide with a firearm and those who committed suicide by an alternative method. METHODS: Suicide data from 1980 to 2005 inclusive, provided by the Central Statistics Office of Ireland, were analysed. For the purpose of this paper, suicide method was collapsed into two groups: firearm assisted suicide (FAS) and non-firearm-assisted suicide (n-FAS). Differences in gender, marital status (married vs not married), area of residence (urban vs rural), agri-employment (agri-employed vs not agri-employed) and age were examined between the two groups. A logistic regression is presented using suicide method (FAS vs n-FAS) as the criterion variable and individual factors as predictors. RESULTS: In total, 9674 suicides were recorded from 1 January 1980 to 31 December 2005. Seven hundred and ninety-three of these were FAS and 8881 were n-FAS. For both suicide profiles, the deceased were predominantly male, living in a rural setting and not married. However, this profile was more salient in the FAS group. In comparison with the n-FAS group, a greater proportion of the FAS decedents were male [chi(2)(1)=152.5, P< or =0.0001, odds ratio (OR)=4.5, 95% confidence interval (CI) 3.4-6.1], from a rural setting [chi(2)(1)=153.5, P< or =0.0001, OR=4.4, 95%CI 3.2-5.6) and agri-employed [chi(2)(1)=21.3, P< or =0.0001, OR=1.5, 95%CI 1.3-1.8). FAS decedents were significantly younger than n-FAS victims, although the size of this effect was small (z=-8.4, P<0.0005, r=-0.1). There was no difference in marital status between the two groups. CONCLUSIONS: Risk factors for FAS should inform policy-making in this area, with particular attention paid to protecting young males resident in rural settings. Consideration should be given to targeting agri-employed individuals as a specific at-risk group. PMID- 20363006 TI - [Pulmonary tuberculosis with the sarcoid cluster sign in high-resolution chest CT]. PMID- 20363007 TI - [Computer-assisted diagnosis in mammography]. PMID- 20363008 TI - Validation of a digital audio recording method for the objective assessment of cough in the horse. AB - AIM: To validate the use of digital audio recording and analysis for quantification of coughing in horses. MATERIALS AND METHODS: Part A: Nine simultaneous digital audio and video recordings were collected individually from seven stabled horses over a 1 h period using a digital audio recorder attached to the halter. Audio files were analysed using audio analysis software. Video and audio recordings were analysed for cough count and timing by two blinded operators on two occasions using a randomised study design for determination of intra-operator and inter-operator agreement. Part B: Seventy-eight hours of audio recordings obtained from nine horses were analysed once by two blinded operators to assess inter-operator repeatability on a larger sample. RESULTS AND CONCLUSIONS: Part A: There was complete agreement between audio and video analyses and inter- and intra-operator analyses. Part B: There was >97% agreement between operators on number and timing of 727 coughs recorded over 78 h. The results of this study suggest that the cough monitor methodology used has excellent sensitivity and specificity for the objective assessment of cough in horses and intra- and inter-operator variability of recorded coughs is minimal. PMID- 20363009 TI - Intra-operative freehand real-time elastography for small focal liver lesions: "visual palpation" for non-palpable tumors. AB - BACKGROUND: Freehand real-time elastography (RTE) has seldom been used to visualize abdominal organs due to their complicated structure and difficulty in freehand compression. We describe a novel, intra-operative imaging system for performing freehand RTE of the liver. METHODS: An RTE system was designed using a spatial, cross-correlation method equipped with a feedback function that checks the quality and quantity of the external compression. Intra-operative freehand RTE was performed for 27 adenocarcinomas, 18 hepatocellular carcinomas (HCCs), and 11 benign lesions after routine B-mode intra-operative ultrasonography (IOUS). Elasticity images were classified into 4 types, from type A (more or comparable strain relative to the background) to type D (no strain), according to the degree of strain contrast with the surrounding liver. We then evaluated the compliance of the RTE findings with the pathologic diagnosis. RESULTS: RTE images were obtained for all the lesions except for 1 metastatic adenocarcinoma. Fourteen of the 18 HCCs were classified as type B or C, with a sensitivity of 83%, a specificity of 76%, and an accuracy of 61%, while 22 of the 26 adenocarcinomas were classified as type D, with a sensitivity of 85%, a specificity of 86%, and an accuracy of 86%. For 15 lesions, clear images were difficult to obtain using B-mode IOUS, whereas RTE visualized clearly the differences in elasticity. CONCLUSION: Our new RTE system facilitated the successful freehand RTE of liver lesions in an intra-operative setting, enabling "visual palpation" during liver surgery and serving as a supportive modality for B mode IOUS. PMID- 20363010 TI - Surgery for intestinal Crohn's disease recurrence. AB - BACKGROUND: Operative therapy for Crohn's disease (CD) recurrence is supposed to be more complex and demanding than primary resection. The purpose of this study was to assess a postoperative course after reoperation for the recurrence of CD. METHODS: From 1998 to 2008, 61 patients underwent reoperation for the recurrence of CD. First, risk factors for postoperative morbidity, with special reference to major postoperative complications, were analyzed. Second, a case-matched study was used to compare the postoperative morbidity of 54 ileocolonic resections for the recurrence of CD (reoperation group) with 57 identical primary ileocolonic resections (primary resection group) according to matching criteria (age, fistulizing or stenotic disease, pre-operative steroids therapy, pre-operative general status, and surgical approach). RESULTS: Postoperative mortality was nil. Postoperative complications were observed in 23 cases (38%). Of these cases, 6 (10%) had major complications (2 anastomotic leakages and 6 intra-abdominal abscesses requiring radiological drainage). Univariate analysis did not identify risk for major complication. None of the 14 patients with temporary stoma developed a major complication (NS). A case-matched study showed a higher morbidity rate (21/54 vs 5/57; P = .0006) with a greater risk of postoperative intra-abdominal abscess (9/59 vs 1/59; P = .007) and a longer postoperative hospital stay in reoperation versus the primary resection group (9 vs 7 days; P < .001). CONCLUSION: Reoperation for CD recurrence is demanding and complex with a frequent need for an associated surgical procedure (because of the severity of the disease and/or adherences). It also is associated with a higher morbidity rate and a longer hospital stay than primary resection. For these reasons, the indication of temporary defunctionning stoma should be discussed systematically in these patients. PMID- 20363011 TI - Photolytic and photocatalytic decomposition of aqueous ciprofloxacin: transformation products and residual antibacterial activity. AB - Previous work demonstrates that widely used fluoroquinolone antibacterial agents, including ciprofloxacin, are degraded by means of aqueous ultraviolet photolytic and titanium dioxide (TiO(2)) photocatalytic (using both ultraviolet-A (UVA) and visible light (Vis) irradiation) treatment processes. In this study, we investigate the effects of photolytic and photocatalytic treatment processes on the antibacterial activity of ciprofloxacin solutions under controlled laboratory conditions. In agreement with earlier work, rates of ciprofloxacin degradation under comparable solution conditions (100microM ciprofloxacin, 0 or 0.5g/L TiO(2), pH 6, 25 degrees C) follow the trend UVA-TiO(2)>Vis-TiO(2)>UVA. Release of ammonia and fluoride ions is observed and a range of organic products have been identified with liquid chromatography-tandem mass spectrometry. However, the identified organic products all appear to retain the core quinolone structure, raising concerns about residual antibacterial potency of the treated solutions. Quantitative microbiological assays with a reference Escherichia coli strain indicate that the antimicrobial potency of ciprofloxacin solutions track closely with the undegraded ciprofloxacin concentration during photolytic or photocatalytic reactions. Quantitative analysis shows that for each mole of ciprofloxacin degraded, the antibacterial potency of irradiated solutions decreases by approximately one "mole" of activity relative to that of the untreated ciprofloxacin solution. This in turn indicates that the ciprofloxacin photo(cata)lytic transformation products retain negligible antibacterial activity relative to the parent compound. The energy demands for achieving one order of magnitude reduction in antibacterial activity within the experimental system are estimated to be 175J/cm(2) (UVA-only), 29J/cm(2) (Vis-TiO(2)), and 20J/cm(2) (UVA TiO(2)), which indicates that the UVA-TiO(2) photocatalysis is the most energy efficient process for achieving ciprofloxacin inactivation under laboratory conditions. PMID- 20363012 TI - A supramolecular bifunctional artificial enzyme with superoxide dismutase and glutathione peroxidase activities. AB - For constructing a bifunctional antioxidative enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, a supramolecular artificial enzyme was successfully constructed by the self-assembly of the Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M Ad) and cyclodextrin-based telluronic acid (2-CD-TeO(3)H) through host-guest interaction in aqueous solution. The self-assembly of the adamantyl moieties of Mn(III) porphyrin and the beta-CD cavities of 2-CD-TeO(3)H was demonstrated by the NMR spectra. In this supramolecular enzyme model, the Mn(III) porphyrin center acted as an efficient active site of SOD and tellurol moiety endowed GPx activity. The SOD-like activity (IC(50)) of the new catalyst was found to be 0.116 microM and equals to 2.56% of the activity of the native SOD. Besides this, supramolecular enzyme model also showed a high GPx activity, and a remarkable rate enhancement of 27-fold compared to the well-known GPx mimic ebselen was observed. More importantly, the supramolecular artificial enzyme showed good thermal stability. PMID- 20363013 TI - Arsenic speciation in municipal landfill leachate. AB - Arsenic species in municipal landfill leachates (MLL) were investigated by HPLC DRC-ICPMS and LC-ESI-MS/MS. Various arsenic species including arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), as well as sulfur-containing organoarsenic species were detected. Two sulfur-containing arsenic species in a MLL were positively identified as dimethyldithioarsinic acid (DMDTA(V)) and dimethylmonothioarsinic acid (DMMTA(V)) by comparing their molecular ions, fragment patterns and sulfur/arsenic ratios with in-house synthesised thiol-organoarsenic compounds. The findings demonstrated the potential for transformation of DMA(V) to DMDTA(V) and DMMTA(V) in a DMA(V)-spiked MLL in a landfill leachate environment. PMID- 20363014 TI - Dating of the Valsequillo volcanic deposits: resolution of an ongoing archaeological controversy in Central Mexico. PMID- 20363015 TI - Fate of 14C-triclocarban in biosolids-amended soils. AB - Triclocarban (TCC) is an antibacterial compound commonly detected in biosolids at parts-per-million concentrations. Approximately half of the biosolids produced in the United States are land-applied, resulting in a systematic release of TCC into the soil environment. The extent of biosolids-borne TCC environmental transport and potential human/ecological exposures will be greatly affected by its bioavailability and the rate of degradation in amended soils. To investigate these factors, radiolabeled TCC ((14)C-TCC) was incorporated into anaerobically digested biosolids, amended to two soils, and incubated under aerobic conditions. The evolution of (14)CO2 (biodegradation) and changes in chemical extractability (bioavailability) was measured over time. Water extractable TCC over the study period was low and significantly decreased over the first 3 weeks of the study (from 14% to 4% in a fine sand soil and from 3 to <1% in a silty clay loam soil). Mineralization (i.e. ultimate degradation), as measured by evolution of (14)CO(2), was <4% over 7.5 months. Methanol extracts of the amended soils were analyzed by radiolabel thin-layer chromatography (RAD-TLC), but no intermediate degradation products were detected. Approximately 20% and 50% of the radioactivity in the amended fine sand and silty clay loam soils, respectively, was converted to bound residue as measured by solids combustion. These results indicate that biosolids-borne TCC becomes less bioavailable over time and biodegrades at a very slow rate. PMID- 20363016 TI - Correlation and association of plasma interleukin-6 and plasma platelet-derived microparticles, markers of activated platelets, in healthy individuals. AB - INTRODUCTION: The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals. MATERIALS AND METHODS: We conducted a cross sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX). RESULTS: By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p=0.015), platelet count (p<0.001), high sensitivity C reactive protein, and the plasma level of IL-6 (p<0.001) in men (R(2)=0.454, p<0.001) and was correlated with platelet count (p<0.001) and the plasma level of IL-6 (p<0.001) in women (R(2)=0.159, p<0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p<0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p<0.001). CONCLUSIONS: These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals. PMID- 20363019 TI - Effects of porcine pre-ovulatory oviductal fluid on boar sperm function. AB - Sperm storage within the oviductal isthmus prior to ovulation typically involves binding to oviductal epithelial cells, which are thought to modulate sperm functions including internal calcium concentration, membrane fluidity, and motility. Around the time of ovulation the spermatozoa are gradually released so that they eventually encounter the oocytes within the oviductal ampulla. Previous studies have shown that the oviductal epithelial cells selectively sequester high quality spermatozoa, but the role of oviductal fluid as a selective modulator of sperm function has been investigated to a lesser extent. Here we address the hypothesis that oviductal fluid is also likely to modulate sperm function. Using samples of porcine oviductal fluid collected in the follicular phase of the estrus cycle, we show that short exposure (20 min to 50 microg/mL of oviductal fluid proteins) to either of two separate proteins fractions (> or < 100 kDa) promotes boar sperm viability and acrosomal integrity, decreases sperm plasma membrane fluidity (measured using merocyanine S540), and increases zona binding and polyspermy during in vitro fertilization. Exposure to the lower molecular fraction significantly inhibited, but did not abolish, the bicarbonate-induced stimulation of motility. The results show that subpopulations of spermatozoa respond differentially to oviductal fluid, and suggest that exposure to oviductal fluid in vivo could exert a further level of functional sperm selection. PMID- 20363020 TI - When is a cow in estrus? Clinical and practical aspects. AB - Good detection of estrus is critically important in dairy husbandry. Incorrect detection of estrus is related to loss of profit due to extended calving intervals, milk loss, veterinary costs, etc. Detection of estrus remains a major problem despites enormous progress in the knowledge of reproductive physiology of the cow and in development of estrus detection aids. To achieve good estrus detection, many factors have to be taken into account. On one hand a cow has to express estrus and on the other hand the farmer has to detect it. Combined action of several hormones causes physiological changes that lead to ovulation and an environment in the uterus that allows sperm to fertilize the egg. Besides these internal actions, a number of external changes can be observed. When using visual observations, time of the day and time spend on observation have a great impact on detection rates. Many devices are available to aid in estrus detection, such as pedometers, mount devices, temperature, and hormone measurements. Expression of estrus can be influenced by many factors. Heritability, number of days postpartum, lactation number, milk production, and health are known to influence estrus expression. Environmental factors like nutrition, season, housing, herd size, etc. also play a role in estrus expression. To evaluate estrus detection, record keeping is very important; a number of formulas can be used to assess detection efficiency. Besides the farmer, the veterinarian and inseminator can play an important role in estrus confirmation and good insemination strategy. In the end, the time of ovulation and the age of the egg at sperm penetration is critical for conception. Therefore, emphasis in research needs to be on the timing of insemination relative to ovulation, and thus on the detection of ovulation. PMID- 20363017 TI - Bevacizumab toxicities and their management in ovarian cancer. AB - OBJECTIVES: The purpose of this review is to discuss the side effect profile of bevacizumab, to discuss proposed mechanisms of these toxicities, and to provide suggestions for management of adverse events. METHODS: A search of MEDLINE and ASCO and SGO abstract databases of articles published between January 1970 and August 2009 addressing the toxicity of bevacizumab in solid tumors was conducted. Reporting was limited to best available evidence including any available phase III studies and ovarian cancer phase II studies. Original publications addressing underlying mechanisms of bevacizumab toxicities were included. RESULTS: Extensive experience with bevacizumab has proven the agent to be generally well tolerated, with an adverse event profile distinct from traditional cytotoxic chemotherapy and likely peculiar to its novel mechanism of action. The most common bevacizumab attributable adverse event, hypertension, can be medically-managed, but more serious adverse events such as bowel perforation require drug discontinuation. CONCLUSIONS: Current best evidence supports the use of bevacizumab in selected patients, and safe administration of bevacizumab requires an understanding of the management of adverse events attributable to its use. PMID- 20363021 TI - Pilot in vivo image spectro-photometric evaluation of optical properties of pure enamel and enamel-dentin complex. AB - OBJECTIVES: The aim of this in vivo study is to investigate the L*a*b*and the opacity (CR) of front teeth by means of an image spectrophotometer and to evaluate the eventual influence of the background color on the results. The second aim is to investigate if there is a relationship between tea, coffee, red wine drinking habits or smoking habits of the test subjects and tooth color. METHODS: A novel image based spectro-photometric approach was developed and applied on a Swiss Army recruits group quantifying L*a*b* of pure enamel as well as of enamel-dentin complex against black and white background together with CR. RESULTS: When 2mm thick pure enamel was considered, the values obtained were (mean (SD)) L*(76.3 (3.4)), a*(3.4 (1.2)) and b*(17.2 (2.45)) against white background and L*(63.5 (4.2)), a*(0.8 (1.3)) and b*(10.7 (2.7)) against black background. The opacity (CR) of 2mm thick pure enamel was (64.4 (0.1)). When 3mm thick enamel-dentin complex was considered, the values obtained were L*(79.0 (2.6)), a*(3.9 (1.3)) and b*(20.4 (3.0)) against a white background and L*(74.9 (3.0)), a*(1.8 (1.2)) and b*(16.7 (3.1)) against a black background. The opacity (CR) of 3mm thick enamel-dentin complex was (87.4 (0.1)). SIGNIFICANCE: The application of this method on a larger group of subjects of different ages may serve as a database for a more exact characterization of optical properties of natural enamel and dentin. PMID- 20363022 TI - Regulating in vivo calcification of alginate microbeads. AB - Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1-6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mm bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification. PMID- 20363023 TI - Surface modification of magnetic nanoparticles using asparagines-serine polypeptide designed to control interactions with cell surfaces. AB - Surface modification is an important part of the fabrication of nanoparticles that have specific properties and functions. Here we describe the development of a functional polypeptide and a simple available technology for surface modification of nanoparticles. A NS polypeptide, which is 100 amino acids composed of repeated units of four asparagine and one serine residue (NS), as a molecule for nanoparticle surface modification was designed. Modification of the surface of a magnetic nanoparticle with the NS polypeptide results in reduction of particle-particle and particle-cell interactions. When NS polypeptide is used in single fusion protein as a linker to display protein G on nanoparticles, the nanoparticle acquires the capacity to specifically bind target cells and to avoid nonspecific adsorption of non-target cells. This technology, incorporating a functional polypeptide, may represent a completely new strategy for surface modification of nanoparticles for use in a variety of cell-associated applications. PMID- 20363024 TI - Abeta20-29 peptide blocking apoE/Abeta interaction reduces full-length Abeta42/40 fibril formation and cytotoxicity in vitro. AB - A key event in the pathogenesis of Alzheimer's disease (AD) is the conversion of the peptide beta-amyloid (Abeta) from its soluble monomeric form into various aggregated morphologies in the brain. Apolipoprotein E (apoE) is known to act as a pathological chaperone of Abeta in this process, promoting its fibril formation from soluble Abeta by binding interaction between carboxy-terminal domain of apoE and residues 12-28 of full-length Abeta. Therefore, blocking apoE/Abeta interaction is being actively pursued as a primary therapeutic strategy for AD. Abeta20-29, a short peptide, contains the residues to competitively bind to apoE and may potentially block the interaction between apoE and full-length Abeta. However, little is known whether Abeta20-29 could block apoE/Abeta interaction to play an effective role in reducing full-length Abeta fibrillization and cytotoxicity. Utilizing fluorescence spectroscopic analysis with thioflavin T and electron microscopic study, we show here that Abeta20-29 alone was non fibrillogenic, and had no direct effects on Abeta1-42 or Abeta1-40 aggregation. Moreover, apoE can directly promote both Abeta1-42 and Abeta1-40 aggregation and fibril formation, while this promoting effect was inhibited when adding Abeta20 29, with a dose-dependent manner. In the series of cell culture experiments, Abeta20-29 alone shows no cytotoxicity to PC12 cells as demonstrated by MTT assay, while co-incubation apoE isoforms and Abeta1-42 or Abeta1-40 shows stronger cytotoxicity as compared to Abeta1-42 or Abeta1-40 alone. When incubated with Abeta20-29, whereas such strong cytotoxic effect was concentration dependently reduced. Taken together, we demonstrate for the first time that Abeta20-29 has no direct effect on full-length Abeta aggregation, and may competitively block the binding of full-length Abeta to apoE, resulting in an inhibitory effect on apoE's promoting full-length Abeta fibrillogenesis and Abeta induced cytotoxicity. Our results raise the possibility that Abeta20-29 peptide blocking the interaction between full-length Abeta and apoE isoforms may be effective as a therapeutic agent for AD. PMID- 20363025 TI - SLC6A4 expression and anti-proliferative responses to serotonin transporter ligands chlomipramine and fluoxetine in primary B-cell malignancies. AB - B-cell lines of diverse neoplastic origin express the serotonin transporter (SERT/SLC6A4) and growth arrest in response to SERT-ligands, including the antidepressants chlomipramine and fluoxetine. Here we detail SLC6A4 transcript (Q PCR) and protein (FACS) expression in primary cells from patients with: chronic lymphocytic leukaemia; mantle cell lymphoma; follicular lymphoma; Burkitt's lymphoma; and diffuse large B-cell lymphoma. The ability of the SERT-binding antidepressants to impact the growth of these cells when sustained on CD154 transfected fibroblasts was also determined. The results reveal a broad spectrum of primary B-cell malignancies expressing SLC6A4 with a proportion additionally displaying growth arrest on SERT-ligand exposure. PMID- 20363026 TI - Interference of nickel with the photosynthetic apparatus of Zea mays. AB - Photosynthetic capacity of plants in heavy metals-polluted environment depends on growth stage of plants. Previously, Ni effect on the process of photosynthesis was studied in fully developed plants. The objective of our studies was the response of the developing photosynthetic apparatus to Ni. Changes in chlorophyll a fluorescence induction kinetics: t(1/2), F(v), F(m), F(0), F(v)/F(m), the content of chlorophyll a, b and carotenoids (x+c), as well as the ratios of chlorophyll (a+b) to the total carotenoids [(a+b)/(x+c)] and chlorophyll a/b (Chl a/b) were followed in leaves of 3 day old seedlings of Zea mays exposed to 0, 100 and 200 microNi for 8 and 13 days. The values of t(1/2), F(v), F(m) markedly declined in seedlings treated with 200 microM Ni for both periods, while the F(v)/F(m) ratio decreased in those exposed to 200 microM Ni for 13 days. The content of (x+c) declined gradually with time of plant exposure to the metal. The (a+b)/(x+c) ratio was reduced under Ni treatment, particularly after 8 days. The Chl a/b ratio increased in seedlings treated with the metal for 8 days, but decreased after 13-day-exposure, indicating different response of Chl b to Ni depending on the exposure time. During growth under Ni stress maize invested primarily in Cars and the reaction centre pigment-Chl a. The protective mechanisms in the Ni stressed plant are discussed. PMID- 20363027 TI - Metabolic responses produced by crude versus dispersed oil in Chinook salmon pre smolts via NMR-based metabolomics. AB - Crude oil spills from tankers remain a serious threat along coastal California. Resource managers require information on the acute toxicity of treated and untreated oil, and their sublethal effects on wildlife. This investigation compared the toxic actions of the water-accommodated fraction (WAF) and the chemically-enhanced WAF (CEWAF; Corexit 9500) of Prudhoe Bay crude oil in pre smolt Chinook salmon (Oncorhynchus tshawytscha) via nuclear magnetic resonance (NMR)-based metabolomics. Metabolite profiles from muscle samples, after 96h exposures, were measured using 1D (1)H NMR and compared via principal component analysis. It was determined that both WAF and CEWAF produced similar profiles in which amino acids, lactate and ATP comprised the highest intensity signals. Overall, metabolic substrates and growth measurements did not show residual effects of short-term exposure on long-term development. In conclusion, the 96h LC(50)s indicate dispersant application significantly decreased hydrocarbon potency and identified metabolites may be bio-indicators of hydrocarbon stress from hydrocarbon exposure. PMID- 20363029 TI - Ocular axial length and its associations in an adult population of central rural India: the Central India Eye and Medical Study. AB - PURPOSE: To investigate the normal distribution of axial length of the globe, which is a major measurement of the eye, and its associations with other ocular and systemic parameters. DESIGN: Population-based study. PARTICIPANTS: The Central India Eye and Medical Study is a population-based study performed in a rural region of central India. The study comprised 4711 subjects (aged 30+ years) of 5885 eligible individuals (response rate, 80.1%). METHODS: A detailed ophthalmic and medical examination was performed. The axial length was measured sonographically. MAIN OUTCOME MEASURES: Axial length. RESULTS: Axial length measurements were available on 4698 study participants (99.7%). Their mean age was 49.4+/-13.4 years (range, 30-100 years), and the mean refractive error was 0.18+/-1.48 diopters (range, -20.0 to +7.25 diopters). Mean axial length was 22.6+/-0.91 mm (range, 18.22-34.20 mm). In multivariate analysis, axial length was significantly (P<0.001) associated with the systemic parameters of increased age, taller body height, greater body mass index, and higher level of education, and with the ocular parameters of lower best-corrected visual acuity, lower corneal refractive power, deeper anterior chamber, thicker lens, and more myopic spherical power and cylindrical refractive power. Within the highly myopic group, as defined by an axial length that exceeded 26.5 mm, none of these associations (except for the association between axial length and spherical refractive power) were statistically significant (P>0.15) in univariate or multivariate analysis. CONCLUSIONS: In a rural population of central India, the mean ocular axial length was 22.6+/-0.91 mm, which was shorter than that of other populations. Axial length was associated with the systemic parameters of increased age, taller body height, greater body mass index, and a higher level of education, and with the ocular parameters of lower best-corrected visual acuity, lower corneal refractive power, deeper anterior chamber, thicker lens, and more myopic spherical and cylindrical refractive power. These associations were valid only for those eyes that were not highly myopic, whereas axial length was associated with refractive error only in highly myopic eyes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 20363028 TI - Mature human neutrophils constitutively express the transcription factor EGR-1. AB - The immediate early response gene, Early Growth Response 1 (EGR-1) has emerged as a central regulator of early inflammatory and immune processes by rapidly regulating the transcription of a wide array of downstream effector genes. Neutrophils, which are among the first circulating leukocytes to respond to inflammatory signals, exhibit a broad set of transcriptional changes immediately upon exposure to inflammatory and pathogenic stimuli. Such transcriptional changes are likely to be controlled by early gene transcription factors such as EGR-1. We therefore examined the regulation and role of EGR-1 in mature human neutrophils exposed to the inflammatory stimuli fMLP and IL-8. We report that human neutrophils rapidly and transiently up-regulate EGR-1 mRNA upon stimulation with fMLP or IL-8. However in contrast to that seen in other cells, EGR-1 mRNA expression profiles were not predictive of protein expression. Instead, we show that human neutrophils constitutively express EGR-1 protein. The cellular content of EGR-1 did not change over time or upon neutrophil activation. Confocal microscopy revealed that EGR-1 was present in both the cytoplasm and nuclei of un stimulated neutrophils and that activation did not change this subcellular localization or promote nuclear translocation. Using chromatin immunoprecipitation, we demonstrate that EGR-1 is associated with the promoter regions of the immune regulatory genes IL-1 beta, TGFbeta-1 and MIF in both resting and activated neutrophils with increased promoter association observed upon cell activation. This novel pattern of EGR-1 protein expression may underlie the ability of the neutrophil to respond rapidly to inflammatory stimuli. PMID- 20363030 TI - Incremental effect for antisocial personality disorder genetic risk combining 5 HTTLPR and 5-HTTVNTR polymorphisms. AB - As the serotonin transporter gene (SLC6A4 or 5-HTT) is a key regulator of central serotonergic activity, several association studies between Antisocial Personality Disorder (APD) and the SLC6A4 polymorphisms have been conducted in the last decade. In the present study, the role of both 5-HTTLPR and 5-HTTVNTR polymorphisms of the SLC6A4 gene in APD is investigated. A sample of 147 male inmates was analyzed. APD was assessed by Aluja's Antisocial Personality Disorder Scale, a measure that correlates 0.73 with the dimensional score of DSM-IV APD and 0.62 with factor II of the Psychopathy Checklist-Revised. Inmates presenting both 5-HTTLPR S/S+S/L and 5-HTTVNTR 12/12 had a higher risk of being classified in the APD group (Odds ratio=3.48). The results also showed that the genotype and haplotype distribution was more dissimilar when extreme groups were compared with odds ratios up to 6.50. Our results supported that, in addition to the widely investigated 5-HTTLPR polymorphism, the 5-HTTVNTR polymorphism might be an interesting candidate for association studies with APD. Results also suggested that previous failures to replicate the association between serotonin transporter gene polymorphisms and APD, or similar phenotypes, could have been due to an under-representation of extremely high APD subjects in the samples analyzed. PMID- 20363031 TI - Lifetime manic-hypomanic symptoms in post-traumatic stress disorder: relationship with the 18 kDa mitochondrial translocator protein density. AB - Initially explored in military settings, post-traumatic stress disorder (PTSD) has shown increasing prevalence in the general population. The high comorbidity rates between bipolar disorder (BD) and PTSD have raised the issue of whether some characteristics of BD could represent risk factors for PTSD. In combat related PTSD, the 18 kDa mitochondrial translocator protein (TSPO), essential for steroid synthesis, was found to be decreased. Aims of the present study were: 1) the assessment of the TSPO mitochondrial density in lymphomonocytes from civilian patients with non-combat-related PTSD, without current or lifetime Axis I mood comorbidity, versus controls; 2) the exploration of the correlations between TSPO density and the presence of comorbid manic/hypomanic lifetime spectrum symptoms. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the Impact of Event Scale (IES), and the lifetime Mood Spectrum Self-Report (MOODS SR). Blood samples were processed to assess TSPO binding parameters in lymphomonocyte mitochondrial membranes. PTSD patients showed a significant decrease in TSPO density, without changes in mitochondrial citrate synthase activity. Further, TSPO density correlated with the number of lifetime manic/hypomanic spectrum symptoms. For the first time, TSPO density was found to be decreased in non-war-related PTSD and such decreases correlated with comorbid manic/hypomanic spectrum symptoms, indicating a possible role of sub-threshold bipolar comorbidity in PTSD-related neurobiological dysregulation. PMID- 20363033 TI - Genetic association of CASP8 polymorphisms with primary progressive multiple sclerosis. AB - We investigated caspase 8 (CASP8) as a candidate gene for multiple sclerosis (MS) susceptibility. Three SNPs (rs2037815, rs12990906 and rs1035140) were genotyped in 546 MS patients and 547 controls. For SNP rs2037815, GG homozygosity was associated with primary progressive multiple sclerosis (PPMS) when compared with relapse-onset MS and controls. We identified risk (GCA) and protective (ACT) haplotypes associated with PPMS when compared with relapse-onset MS and controls. GG homozygosity for SNP rs2037815 in PPMS patients was associated with a trend towards faster disease progression. These findings point to a role of CASP8 polymorphisms in the MS genetic risk in PPMS patients. PMID- 20363032 TI - Molecular and structural characterisation of a macrophage migration inhibitory factor from sea bass (Dicentrarchus labrax L.). AB - The macrophage migration inhibitory factor (MIF) is a cytokine produced in numerous cell types, mainly T lymphocytes and macrophages, in response to inflammatory stimuli. In this paper we report the identification of a cDNA encoding a MIF molecule from sea bass (Dicentrarchus labrax L.), its expression analysis and its 3D structure obtained by template-based modelling. The sea bass MIF cDNA consists of 609bp that translates in one reading frame to give the entire molecule containing 115 amino acids. The sequence contains three cysteine residues in conserved positions compared to human MIF and most Teleost fishes, with the exception of zebrafish and carp. The Cys(57)-Ala(58)-Leu(59)-Cys(60) motif, present inside the stretch important for JAB1-interaction and mediator of the thiol-protein oxidoreductase activity of MIF, is conserved in sea bass, together with the Pro(2) residue that is crucial for the tautomerase catalytic activity. Real-time PCR analyses revealed that MIF is constitutively expressed in all selected tissues and organs, with the highest mRNA level observed in thymus. MIF expression was induced after 4h in vitro stimulation of head kidney leukocytes with LPS and decreased after 24h. The predicted 3D model of sea bass MIF has been used to verify the presence of structural requirements for its known biological activities. PMID- 20363034 TI - Selective fiberoptic left main-stem intubation to treat bronchial laceration in an extremely low birth weight neonate. AB - A neonate born at 24 weeks gestation developed a right tension pneumothorax that persisted despite the placement of multiple thoracostomy tubes, the use of high frequency ventilation and postural therapy. On day-of-life 11, bedside bronchoscopy revealed a laceration at the junction of the trachea and right main stem bronchus. Under fiberoptic guidance the left main-stem bronchus was intubated. Single-lung ventilation then was employed for 24h, after which time the pneumothorax never recurred. We postulate that the diversion of positive pressure ventilation away from the laceration site allowed the surrounding injury induced granulation tissue to create a seal and facilitate closure of the defect. PMID- 20363035 TI - Endoscopic laterofixation in bilateral vocal cords paralysis in children. AB - INTRODUCTION: Vocal cords paralysis is the second most frequent cause of laryngeal stridor in children. Symptoms of congenital vocal cords paralysis can occur shortly after birth or later. Vocal cords paralysis can be unilateral or bilateral. Symptoms of unilateral paralysis include hoarse weeping or stridor during a deep inhalation. In children unilateral vocal cords paralysis often retreats spontaneously or can be completely compensated. Children with bilateral vocal cords paralysis present mainly breathing disorders while phonation is normal. Symptoms are different, starting from complete occlusion of respiratory tracts and ending on small symptoms connected with the lack of effort tolerance. When symptoms are severe, patients from this group require a tracheotomy. The lack of restoration of normal function of vocal cords or lack of complete compensation and maintenance of symptoms are an indication for surgical treatment. OBJECTIVE: The aim of this study is to present results of the treatment of bilateral vocal cords paralysis in children using the endoscopic method of laterofixation of vocal cords. MATERIAL AND METHODS: In the Pediatric ENT Department between 1998 and 2009 sixty four children with dyspnoea and/or phonation disorders caused by vocal cords paralysis were treated. RESULTS: In ten cases laterofixation of vocal cords was performed, in most cases with good result. In this article the authors present the method of endoscopic laterofixation and achieved results. CONCLUSIONS: Endoscopic laterofixation of vocal cords in children is a safe and an easy method of surgical treatment of bilateral vocal cords paralysis. This method can be used as a first and often as a one stage treatment of vocal cords paralysis. In some cases this procedure is insufficient and has to be completed with other methods. PMID- 20363036 TI - Head and neck manifestation and prognosis of Langerhans' cell histiocytosis in children. AB - OBJECTIVE: To appreciate the several head and neck manifestations of Langherans' cell histiocytosis (LCH) in children and their multidisciplinary management and outcome. STUDY DESIGN: Retrospective study. PATIENTS AND METHODS: Clinical reports of 42 patients with LCH treated in the Departments of Paediatric Haematology, Paediatric Oncology and Paediatric Otorhinolaryngology of a tertiary care center were analyzed. Only cases where the disease was localized to the head and neck were considered. The age at diagnosis, gender, clinical presentation, extension of disease as well as response to treatment and outcome were recorded from the charts of each of these patients. RESULTS: Of the 42 patient charts reviewed, 31 (73.8%) presented with head and neck localization. 10 of these had an exclusive head and neck presentation. Multisystem LCH was mostly found in infants under 3-year-old (mean age: 2-year-old), and bony manifestations in older. All treatments delivered to patients were well-tolerated and the evolution good. DISCUSSION AND CONCLUSION: Head and neck involvement is known to be very frequent in LCH. There is no consensus about treatment but authors highlight that all teams in charge of patients presenting with LCH agree to remain as conservative as possible. For solitary large lesions looking like a tumor which resection could result in functional or cosmetic morbidity, it would be important to get first a biopsy. For multisystemic LHC, therapeutic trials with chemotherapy agents still in process should increase the rate of success. PMID- 20363037 TI - Preoperative cerebral magnetic resonance imaging and white matter changes in pediatric cochlear implant recipients. AB - INTRODUCTION: Preoperative magnetic resonance imaging (MRI) can yield valuable information regarding the status of the inner ear in pediatric cochlear implant (CI) candidates. Incidentally, cerebral white matter changes are at times noted on these MRI scans. They may indicate post-infectious/postinflammatory changes or progressive neurodegenerative processes. OBJECTIVE: To evaluate the clinical significance of cerebral white matter changes in pediatric CI patients. METHODS: Retrospective chart review of pediatric CI recipients with preoperative MRI between March 2004 and January 2009 was performed. MRI reports along with postoperative audiology and speech and language outcomes were assessed. RESULTS: Fifty-seven patients were included in the study. There were 29 females and 28 males. Mean age was 58 months (range of 12-194 months). Abnormal MRI with varying degrees of white matter changes was noted in 10 (18%) children. Neurological assessments did not reveal any serious central nervous system diseases. Two of the 10 patients demonstrated significant delays and difficulties with postoperative CI performance. CONCLUSIONS: Cerebral white matter abnormalities are not uncommon incidental findings in preoperative MRI scans in pediatric CI candidates. These changes may reflect remote or active pathology which may require neurological assessment. The significance of these findings is still uncertain and should be better clarified as we study more patients. PMID- 20363039 TI - Trenbolone causes irreversible masculinization of zebrafish at environmentally relevant concentrations. AB - Feminization of fish caused by certain estrogenic compounds e.g. 17 alpha ethinylestradiol (EE2) has been shown to be partly reversible. So far it has not been studied if this applies for androgenic compounds too. The androgenic steroid trenbolone acetate (TbA) is used as growth promoter in beef cattle in the United States, South America, and Australia. TbA metabolites are stable in animal waste and have been detected in surface waters associated with feedlot areas and studies on both fish and mammals have demonstrated a strong androgenic effect of those metabolites. Zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of the TbA metabolite 17beta-trenbolone from 0 to 60 days post-hatch (dph) and either sacrificed at 60 dph, transferred to clean water for 170 days or kept in exposure for 170 days. At 60 dph gonadal histology and vitellogenin analyses revealed all-male populations in groups exposed to 15.5 and 26.2 ng/L, and at 9.2 ng/L a skewed sex ratio towards males was observed. After the depuration period no sign of reversibility was observed. Environmentally relevant concentrations of 17beta-trenbolone cause a strong and irreversible masculinization of zebrafish and that raises concern about the effects of androgenic discharges in the aquatic environment. In addition this study also aids in understanding of the so far unknown sex determination process in zebrafish. PMID- 20363040 TI - Effect of classifying disease states in genetic association studies for paratuberculosis. AB - Genetic association studies are a means to elucidate underlying genetic regulation of host-pathogen interaction, immune response, and the fate of infection. Diseases such as paratuberculosis in cattle lack definitive diagnostic criteria, thereby complicating the definition of infection status as an outcome for genetic association studies. A study was performed to evaluate the potential bias in estimates of effect and differences in statistical power associated with parallel test interpretation, latent probability of infection adjusted for imperfect test sensitivity and specificity, and multinomial outcomes in cohorts of cattle simulated using Monte Carlo sampling methods. Test results were simulated for microbial culture of feces for Mycobacterium avium subsp. paratuberculosis (MAP) and serum ELISA for anti-MAP antibody using estimates of test sensitivity and specificity. A range of disease allele frequencies and levels of association were considered. Case-control study populations were drawn from the simulated cohorts and the association between the disease allele and infection status was evaluated using logistic regression for binary outcomes and polytomous regression for multinomial outcomes. For the majority of the classification and analytical methods evaluated, estimates of effect were biased toward the null. Frequentist approaches to analysis of the latent probability of infection and multinomial classifications based upon results of culture of feces for MAP demonstrated the smallest degree of bias. Power to detect associations was generally low for all models, but improved with larger effects and higher allele frequencies. Imperfect specificity of serum ELISA was a major factor in the degree of bias observed and statistical power. The results of this study indicate that the method of classifying infection status must be considered carefully in genetic association studies for paratuberculosis and other diseases with similar challenges in defining infection status, and study designs should be modified to accommodate relative advantages and disadvantages of available methods. PMID- 20363038 TI - Dendritic ion channel trafficking and plasticity. AB - Dendritic ion channels are essential for the regulation of intrinsic excitability as well as modulating the shape and integration of synaptic signals. Changes in dendritic channel function have been associated with many forms of synaptic plasticity. Recent evidence suggests that dendritic ion channel modulation and trafficking could contribute to plasticity-induced alterations in neuronal function. In this review we discuss our current knowledge of dendritic ion channel modulation and trafficking and their relationship to cellular and synaptic plasticity. We also consider the implications for neuronal function. We argue that to gain an insight into neuronal information processing it is essential to understand the regulation of dendritic ion channel expression and properties. PMID- 20363041 TI - Dose-rate effects in external beam radiotherapy redux. AB - Recent developments in external beam radiotherapy, both in technical advances and in clinical approaches, have prompted renewed discussions on the potential influence of dose-rate on radio-response in certain treatment scenarios. We consider the multiple factors that influence the dose-rate effect, e.g. radical recombination, the kinetics of sublethal damage repair for tumors and normal tissues, the difference in alpha/beta ratio for early and late reacting tissues, and perform a comprehensive literature review. Based on radiobiological considerations and the linear-quadratic (LQ) model we estimate the influence of overall treatment time on radio-response for specific clinical situations. As the influence of dose-rate applies to both the tumor and normal tissues, in oligo fractionated treatment using large doses per fraction, the influence of delivery prolongation is likely important, with late reacting normal tissues being generally more sensitive to the dose-rate effect than tumors and early reacting tissues. In conventional fractionated treatment using 1.8-2Gy per fraction and treatment times of 2-1 min, the influence of dose-rate is relatively small. Lastly, the dose-rate effect in external beam radiotherapy is governed by the overall beam-on-time, not by the average linac dose-rate, nor by the instantaneous dose-rate within individual linac pulses which could be as high as 3 x 10(6)MU/min. PMID- 20363042 TI - Culture-independent techniques applied to food industry water surveillance--a case study. AB - Culture-independent techniques were used for the detection of pathogenic bacteria in drinking water at potentially critical control points along the production lines at a German dairy company and a Spanish dry cured ham company. Denaturing gradient gel electrophoresis (DGGE) was used to describe bacterial population shifts indicating biological instability in the drinking water samples. Autochthonous bacteria were identified by sequencing the excised DGGE DNA bands. More specifically, real-time PCR was applied to detect a number of pathogenic bacteria, i.e. Listeria monocytogenes, Mycobacterium avium subsp. paratuberculosis, Campylobacter jejuni, Enterococcus spp., Salmonella spp, Escherichia coli, and Pseudomonas aeruginosa. Due to the detection limits of the real-time PCR method, a specific protocol was established in order to meet the technical detection requirements and to avoid unwanted polymerase inhibitions. Autochthonous bacterial populations were found to be highly stable at most of the sampling points. Only one sampling point exhibited population shifts at the German dairy company. Enterococci and P.aeruginosa were detected in some water samples from these companies by molecular biology detection methods, but not by conventional culturing methods. Some opportunistic bacteria as Enterobacter sp., Acinetobacter, Sphingomonas sp. and non-pathogenic Bacillus, were also detected after DNA sequencing of DGGE bands. PMID- 20363043 TI - Validating ICD coding algorithms for diabetes mellitus from administrative data. AB - AIM: To assess validity of diabetes International Classification of Disease (ICD) 9 and 10 coding algorithms from administrative data using physicians' charts as the 'gold standard' across time periods and geographic regions. METHODS: From 48 urban and 16 rural general practitioners' clinics in Alberta and British Columbia, Canada, we randomly selected 50patient charts/clinic for those who visited the clinic in either 2001 or 2004. Reviewed chart data were linked with inpatient discharge abstract and physician claims administrative data. We identified patients with diabetes in the administrative databases using ICD-9 code 250.xx and ICD-10 codes E10.x-E14.x. RESULTS: The prevalence of diabetes was 8.1% among clinic charts. The coding algorithm of "2 physician claims within 2 years or 1 hospitalization with the relevant diabetes ICD codes" had higher validity than other 7 algorithms assessed (sensitivity 92.3%, specificity 96.9%, positive predictive value 77.2%, and negative predictive value 99.3%). After adjustment for age, sex, and comorbid conditions, sensitivity and positive predictive values were not significantly different between time periods and regions. CONCLUSION: Diabetes could be accurately identified in administrative data using the following case definition "2 physician claims within 2 years or 1 hospital discharge abstract record with diagnosis codes 250.xx or E10.x-E14.x". PMID- 20363045 TI - stab: an R package for drug stability data analysis. AB - In the pharmaceutical industry, drug stability studies are routinely performed to measure the degradation of an active pharmaceutical ingredient (API) within a drug product. The purpose of drug stability studies is to examine how the API in a drug product varies with time under influence of a variety of environmental factors. The most important study is to establish the expiration date (i.e., the shelf life) of the product. Thus, the aim of this study was to develop an R package to calculate the shelf life based on drug stability data according to the suggested algorithms by ICH Tripartite Guidelines for Q1E Evaluation. PMID- 20363044 TI - Initiation with once-daily BIAsp 30 results in superior outcome compared to insulin glargine in Asians with type 2 diabetes inadequately controlled by oral anti-diabetic drugs. AB - We compare the efficacy and safety of once-daily biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine in Asian subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs (OADs). In a 26-week, open labelled, randomised, parallel-group, multinational, multicentre, treat-to-target trial, 155 insulin-naive Asian subjects were treated with either BIAsp 30 or insulin glargine, both in combination with metformin and glimepiride. Change in HbA(1c) at end of treatment with BIAsp 30 was superior to insulin glargine (BIAsp 30-glargine=-0.36%, 95% CI [-0.64; -0.07], p=0.015). Mean self-measured plasma glucose (SMPG) at bedtime was significantly lower with BIAsp 30 than insulin glargine (7.98+/-0.34 mmol/L vs. 9.16+/-0.33 mmol/L, p=0.0078). Incidences of minor and daytime hypoglycaemia were higher with BIAsp 30 than those with glargine, but the difference did not reach the statistical significance. No difference was seen in nocturnal hypoglycaemia. The incidence of adverse events was comparable between treatments, with low incidence of serious adverse events and major hypoglycaemia. Mean body weight increased slightly in both groups. In insulin-naive Asian subjects with type 2 diabetes who are inadequately controlled with OADs, once-daily BIAsp 30 is superior to insulin glargine. PMID- 20363046 TI - Association between lymphangiogenesis-/micrometastasis- and adhesion-related molecules in resected stage I NSCLC. AB - BACKGROUND: The purpose of this study was to clarify the role and clinical significance of lymphangiogenesis/micrometastases and adhesion molecules in resected stage I non-small cell lung cancer (NSCLC). METHODS: Immunohistochemical (IHC) staining was used to analyze the protein expression of vascular endothelial growth factor-C (VEGF-C), VEGF, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in paraffin-embedded tumor samples from 117 well-characterized stage I NSCLC patients and to compare the protein expression, clinical variables and survival outcome. As a micrometastatic parameter in lymph nodes (LNs), cytokeratin (CK) staining was performed. RESULTS: The positive expression of VEGF C and VEGF were detected in 54 (48.7%) and 86 (73.5%), respectively. We identified micrometastatic tumor cells in pathological N0 LNs in 34 (29.1%) of 117 patients. E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin were identified in 70 (59.8%), 41 (35.0%), 83 (70.9%), and 61 (52.1%) specimens, respectively. The VEGF-C expression was found more frequently in squamous cell carcinoma (SQ) and in the tumors with negative expression of beta-catenin than counter features. The VEGF expression was found more frequently in the tumors with a negative expression of E-cadherin. Micrometastasis was found more frequently in a pathological T2 status and in the tumors with a negative expression of alpha-catenin. Beta-catenin and gamma-catenin expressions were found less and more frequently in SQ, respectively. A univariate and multivariate survival analysis demonstrated that old age, pathological T2 status, and micrometastasis were independently associated with an increased risk of poor survival in the patients who underwent a surgical resection of stage I NSCLC. CONCLUSIONS: Complicated relationships exist between lymphangiogenesis/micrometastases and adhesion molecules with a specific histology. The detection of lymph nodal micrometastasis by CK may therefore be a useful marker for predicting a poor prognosis in patients who undergo a complete resection of stage I NSCLC. PMID- 20363047 TI - Evolutionary stasis: the stable chromosomes of birds. AB - Evolution at the molecular level is manifested in a variety of types of change in DNA sequences, including changes in the structure and organisation of chromosomes. However, in birds chromosomal evolution occurs at an unusually slow rate and recent whole-genome comparisons have shown that many chromosomes have remained more or less intact during avian evolution. Here I discuss progress in the development of genetic maps of natural bird populations, which has revealed that the evolutionary stasis of chromosomes often extends to conservation of gene order. The evolutionary stability of bird chromosomes, which might relate to a low frequency of transposable elements, will facilitate the transfer of genomic information from model to non-model organisms and might have a connection to the rarity of postzygotic incompatibilities observed in birds. PMID- 20363048 TI - Surveillance and endemic vancomycin-resistant enterococci: some success in control is possible. AB - Vancomycin-resistant enterococci (VRE) are prevalent in many Irish hospitals. We analysed surveillance data from 2001 to 2008 in a centre where VRE is endemic. All clinically significant enterococci were tested for susceptibility to vancomycin. All intensive care unit admissions were screened on admission and weekly thereafter. Interventions included isolating/cohorting VRE patients, monthly prevalence surveys of VRE patients, the introduction of an electronic alert system, programmes to improve hand and environmental hygiene, and the appointment of an antibiotic pharmacist. There was a significant increase in the number of positive VRE screening samples from 2001 (1.96 patients with positive VRE screens per 10 000 bed-days) to 2006 (4.98 per 10 000 bed-days) (P < or = 0.001) with a decrease in 2007 (3.18 per 10 000 bed-days) (P < or = 0.01). The number of VRE bloodstream infections (BSI) increased from 0.09 BSI per 10 000 bed days in 2001 to 0.78 per 10 000 bed-days in 2005 (P < or = 0.001) but decreased subsequently. Linear regression analysis indicated a significant association between new cases of VRE and non-isolated VRE patients, especially between May 2005 and December 2006 [P=0.009; 95% confidence interval (CI): 0.08-0.46] and between May 2005 and December 2008 (P = 0.008; 95% CI: 0.06-0.46). Routine surveillance for VRE together with other measures can control VRE BSI and colonisation, even where VRE is endemic, and where facilities are constrained. PMID- 20363049 TI - Bacterial flora on cell phones of health care providers in a teaching institution. AB - We conducted a cross-sectional study involving culture of cell phones of 288 health care providers (HCP) during a 6-month period. One hundred nine (43.6%) HCP carried infective organisms on their cell phones. It is recommended that cell phones be cleaned regularly. PMID- 20363051 TI - A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient. AB - Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype. PMID- 20363052 TI - Disturbed sleep/wake rhythms and neuronal cell loss in lateral hypothalamus and retina of mice with a spontaneous deletion in the ubiquitin carboxyl-terminal hydrolase L1 gene. AB - Many neurodegenerative disorders including Parkinson's disease (PD) and Alzheimer's disease (AD) are associated with sleep disturbances with presumably multifactorial etiology. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is involved in the pathophysiology of PD and AD. In the present study, we analyzed locomotor rhythms, orexin A-immunoreaction (Ir) in the lateral hypothalamus (LH) and melanopsin-Ir in the retina of gracile axonal dystrophy (gad) mice with a spontaneous deletion in the Uch-l1 gene. In constant darkness, gad mice showed circadian rhythms in locomotor activity, indicating the integrity of the endogenous circadian rhythm generator. However, gad mice showed an increased activity during subjective day and a decreased number of orexin A-immunoreactive neurons in the LH compared with the wild type (WT). In addition, gad mice showed increased locomotor activity in the light period when kept in a standard photoperiod and entrainment to phase shifts was significantly slower than in WT. Moreover, melanopsin-Ir was significantly reduced in the retina of gad mice, suggesting an impairment of circadian light perception in gad mice. PMID- 20363050 TI - Age-related decline in white matter tract integrity and cognitive performance: a DTI tractography and structural equation modeling study. AB - Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging. PMID- 20363053 TI - Heritability of brain ventricle volume: converging evidence from inconsistent results. AB - Twin studies generally show great consistency for the heritability of brain structures. Ironically, the lateral ventricles--perhaps the most reliably measured brain regions of interest--are the most inconsistent when it comes to estimating genetic influences on their volume. Heritability estimates in twin studies have ranged from zero to almost 0.80. Here we aggregate heritability estimates from extant twin studies, and we review and reinterpret some of the findings. Based on our revised estimates, we conclude that lateral ventricular volume is indeed heritable. The weighted average heritability of the revised estimates was 0.54. Although accumulated environmental insults might seem most logical as the predominant cause of age-related ventricular expansion, the data strongly suggest that genetic influences on lateral ventricular volume are increasing with age. Genetic influences accounted for 32-35% of the variance in lateral ventricular volume in childhood, but about 75% of the variance in late middle and older age. These conclusions have implications for the basic understanding of the genetic and environmental underpinnings of normative and pathological brain aging. PMID- 20363054 TI - [Hepatitis B reactivation in an HbsAg-negative/anti-HBc-positive patient with B cell non-Hodgkin lymphoma receiving chemotherapy with rituximab]. AB - Reactivation of hepatitis B virus infection in patients with resolved infection is rare and is usually associated with immunosuppressive therapy. Morbidity and mortality are high. Some cases of hepatitis B reactivation associated with the use of rituximab have previously been published. We present the case of a patient with B-cell non-Hodgkin lymphoma receiving combination chemotherapy with rituximab who showed hepatitis B reactivation followed by liver failure. The most recent literature on this topic is reviewed and discussed. PMID- 20363055 TI - Adenocarcinoma of the colon associated with hyperplastic polyposis. PMID- 20363056 TI - [Liver transplantation in patients with HIV infection]. AB - During the few last years, after the introduction of high activity antiretroviral therapy (HAART), liver diseases, particularly those related to HCV infection, have emerged as one of the most important causes of mortality in patients with HIV infection. Consequently, liver transplantation is increasingly indicated in this population. Post-transplantation survival in HIV-positive patients with non hepatitis C virus (HCV) liver diseases is adequate and similar to that in HIV negative patients. In contrast, survival in patients coinfected with HIV and HCV is only moderate (around 50% at 5 years after transplantation). The main cause of mortality in these patients is HCV recurrence. In almost all patients, HIV infection remains controlled with HAART after liver transplantation. Other issues of interest in this setting are the selection of liver transplantation candidates and the frequent interactions between HAART and immunosuppressive drugs. PMID- 20363057 TI - [Bertiella studeri infection in a girl from Equatorial Guinea]. PMID- 20363058 TI - [Telomeres and telomerase: relevance and future prospects in systemic lupus erythematosus]. AB - Telomeres are specialized structures that cap and protect the end of chromosomes. Telomeres progressively shorten after each cellular division unless an enzyme, the telomerase, counteracts. Telomeres are implicated in cellular senescence, acting like a biological clock. Telomere length and telomerase activity are important in the physiopathology of cancer. In the past years, research has focused on them in order to find new therapeutic targets. Yet, oxidative stress, inflammation and increased leucocytes renewal are major environmental factors associated with telomeres shortening acceleration and thus in concordance with biological age. Thus, telomeric erosion induces cell apoptosis; indeed, apoptotic cell clearance is impaired in systemic lupus. Considering these elements and data resulting from oncology, telomere/telomerase couple was studied during the last decade in systemic lupus erythematosus. The objective was to know if this couple could have an implication in the physiopathology of this disease. A systematic review of literature is proposed about telomere and/or telomerase in systemic lupus erythematosus in order to discuss their physiopathological implication. Among 273 tested patients, telomere seems to be eroded and telomerase activity insufficiently increased but correlated to the activity of the disease. The analysis of telomere length and telomerase activity could be useful as prognosis factor or disease activity index. Telomere erosion could reflect an accelerated replicative senescence of the immune system. The role of the regulator T lymphocytes has not yet been precised. Standardized studies on larger population could be realized in systemic lupus and open new avenues of research and/or therapy based upon the telomere/telomerase biology. PMID- 20363060 TI - A comparative study of A1 pulley compliance. AB - BACKGROUND: Trigger finger is most common in the ring finger, but the reason for this is not known. We hypothesized that the compliance of the A1 pulley might be one of the factors responsible for this phenomenon. The purpose of this study was therefore to compare the compliance of the normal A1 pulley of the thumb, index, middle, ring and little fingers using human cadavers. METHODS: Eight normal thumbs, index, middle, ring and little fingers from eight fresh frozen human hand cadavers were used in this experiment. The compliance of the A1 pulley was measured by the resistance when passing a tapered metal rod through the A1 pulley. The slopes of the linear region of radial force/increasing area ratio curve were calculated and analyzed. FINDINGS: The mean slope of the linear region of the radial force/increasing area ratio curve was significantly different among the five digits (p<0.05). Post hoc analysis indicated that the mean slope for the middle finger A1 pulleys was larger than the thumb and little finger A1 pulleys (p<0.05). INTERPRETATION: The findings did not support our clinical hypothesis that A1 pulley stiffness would parallel the relative frequency of trigger finger by digit. PMID- 20363059 TI - Maternal diet and cord blood leptin and adiponectin concentrations at birth. AB - BACKGROUND & AIMS: The purpose of this study was to determine the effects of total energy intake, macronutrient intake, and maternal adherence to Mediterranean diet or Alternative Healthy Eating Index (AHEI) on cord blood leptin and adiponectin levels, which have been associated with childhood adiposity. METHODS: We used multivariable linear regression to assess associations of maternal diet, averaged over 1st and 2nd trimesters, with cord blood adipokines of 780 women from the prospective cohort study Project Viva. RESULTS: Mean (SD) energy intake during pregnancy was 2135 (596) kcal. Mean (SD) cord blood levels of leptin and adiponectin were 9.0 (6.6) ng/ml and 28.6 (6.7) MUg/ml, respectively. Neither closer adherence to a Mediterranean/AHEI pattern diet nor energy intake was associated with either cord blood leptin or adiponectin. Protein intake was associated with both marginally lower leptin ( 0.22 ng/ml [95% CI -0.41, -0.02] for each 1% of energy) and adiponectin (-0.25 MUg/ml [95% CI -0.48, -0.02]). CONCLUSIONS: Closer adherence to a Mediterranean/AHEI pattern diet during pregnancy was not associated with cord blood leptin or adiponectin. Maternal protein intake was weakly but significantly associated with lower cord blood leptin and adiponectin. PMID- 20363061 TI - Relations between mercury, methyl-mercury and selenium in tissues of Octopus vulgaris from the Portuguese coast. AB - Mercury, methyl-mercury (MeHg) and selenium were determined in digestive gland and mantle of Octopus vulgaris, from three areas of the Portuguese coast. To our knowledge these are the first data on MeHg in cephalopods. Concentrations were higher in the digestive gland and percentage of MeHg in mantle. Enhanced Hg and MeHg levels were obtained in digestive gland of specimens from Olhao (3.1-7.4 and 2.0-5.0 microg g(-1), respectively). Differences between areas may be partially related to Hg availability. Relationships between concentrations in mantle and digestive gland pointed to proportional increases of Hg and MeHg in tissues of specimens from Matosinhos and Cascais, but relatively constant values in mantle of individuals from Olhao (higher contamination). Se:Hg molar ratio in digestive gland was 32 and 30 in octopus from Matosinhos and Cascais, respectively, and 5.4 from Olhao. The proximity to the unit suggests demethylation as response to elevated MeHg levels in digestive gland. PMID- 20363062 TI - Experimental exposure to cadmium affects metallothionein-like protein levels but not survival and growth in wolf spiders from polluted and reference populations. AB - Both local adaptation and acclimation in tolerance mechanisms may allow populations to persist under metal pollution. However, both mechanisms are presumed to incur (energetic) costs and to trade-off with other life-history traits. To test this hypothesis, we exposed Pardosa saltans (Lycosidae) spiderlings originating from metal-polluted and unpolluted sites to a controlled cadmium (Cd) treatment, and compared contents of metal-binding metallothionein like proteins (MTLPs), internal metal concentrations, and individual survival and growth rates with a reference treatment. While increased MTLP concentrations in offspring originating from both polluted and unpolluted populations upon exposure indicates a plastic tolerance mechanism, survival and growth rates remain largely unaffected, independent of the population of origin. However, MTLP and Cd concentrations were not significantly correlated. We suggest that MTLP production may be an important mechanism enabling P. saltans populations to persist in ecosystems polluted with heavy metals above a certain level. PMID- 20363064 TI - International involvement and national health governance: the basic benefit package in Tajikistan. AB - Tajikistan, a Central Asian state of 7.4 million inhabitants, is facing particular health policy challenges: not only is the country the poorest of the former Soviet republics, but its capacity to deal with post-communist transition and economic crisis has been further undermined through civil war and large-scale migration. This paper, examining the introduction of the basic benefit package and formal co-payments, elucidates how international involvement in Tajikistan's health sector has impacted on national health governance. Based on documentary sources and information provided by key informants, we find that external agencies have both strengthened and weakened national health governance. Although they have played a major part in supporting Tajikistan's health sector, these efforts have often been fragmented, as donor coordination was at times less than optimal. A key challenge for national health governance is the limited technical and institutional capacity of the Ministry of Health and further efforts are needed to build national capacity. PMID- 20363065 TI - Lung function testing in pre-school children. PMID- 20363063 TI - Upward spirals of positive emotions counter downward spirals of negativity: insights from the broaden-and-build theory and affective neuroscience on the treatment of emotion dysfunctions and deficits in psychopathology. AB - This review integrates Fredrickson's broaden-and-build theory of positive emotions with advances in affective neuroscience regarding plasticity in the neural circuitry of emotions to inform the treatment of emotion deficits within psychopathology. We first present a body of research showing that positive emotions broaden cognition and behavioral repertoires, and in so doing, build durable biopsychosocial resources that support coping and flourishing mental health. Next, by explicating the processes through which momentary experiences of emotions may accrue into self-perpetuating emotional systems, the current review proposes an underlying architecture of state-trait interactions that engenders lasting affective dispositions. This theoretical framework is then used to elucidate the cognitive-emotional mechanisms underpinning three disorders of affect regulation: depression, anxiety, and schizophrenia. In turn, two mind training interventions, mindfulness and loving-kindness meditation, are highlighted as means of generating positive emotions that may counter the negative affective processes implicated in these disorders. We conclude with the proposition that positive emotions may exert a countervailing force on the dysphoric, fearful, or anhedonic states characteristic of psychopathologies typified by emotional dysfunctions. PMID- 20363066 TI - Effect of impeller type and agitation on the performance of pilot scale ASBR and AnSBBR applied to sanitary wastewater treatment. AB - The objective of this work was to assess the effect of agitation rate and impeller type in two mechanically stirred sequencing batch reactors: one containing granulated biomass (denominated ASBR) and the other immobilized biomass on polyurethane foam (denominated AnSBBR). Each configuration, with total volume of 1 m(3), treated 0.65 m(3) sanitary wastewater at ambient temperature in 8-h cycles. Three impeller types were assessed for each reactor configuration: flat-blade turbine impeller, 45 degrees -inclined-blade turbine impeller and helix impeller, as well as two agitation rates: 40 and 80 rpm, resulting in a combination of six experimental conditions. In addition, the ASBR was also operated at 20 rpm with a flat-blade turbine impeller and the AnSBBR was operated with a draft tube and helix impeller at 80 and 120 rpm. To quantify how impeller type and agitation rate relate to substrate consumption rate, results obtained during monitoring at the end of the cycle, as well as the time profiles during a cycle were analyzed. Increasing agitation rate from 40 rpm to 80 rpm in the AnSBBR improved substrate consumption rate whereas in the ASBR this increase destabilized the system, likely due to granule rupture caused by the higher agitation. The AnSBBR showed highest solids and substrate removal, highest kinetic constant and highest alkalinity production when using a helix impeller, 80 rpm, and no draft tube. The best condition for the ASBR was achieved with a flat-blade turbine impeller at 20 rpm. The presence of the draft tube in the AnSBBR did not show significant improvement in reactor efficiency. Furthermore, power consumption studies in these pilot scale reactors showed that power transfer required to improve mass transfer might be technically and economically feasible. PMID- 20363069 TI - Molecular mechanisms underlying tumor dormancy. AB - Evidence suggests that dormant, microscopic tumors are not only common, but are highly prevalent in otherwise healthy individuals. Due to their small size and non-invasive nature, these dormant tumors remain asymptomatic and, in most cases, undetected. With advances in diagnostic imaging and molecular biology, it is now becoming clear that such neoplasms can remain in an asymptomatic, dormant stage for considerable periods of time without expanding in size. Although a number of processes may play a role in thwarting the expansion of microscopic tumors, one critical mechanism behind tumor dormancy is the ability of the tumor population to induce angiogenesis. Although cancer can arise through multiple pathways, it is assumed that essentially most tumors begin as microscopic, non-angiogenic neoplasms which cannot expand in size until vasculature is established. It is now becoming clear that cancer does not progress through a continuous exponential growth and mass expansion. Clinical cancer is usually manifested only in late, unavoidably symptomatic stages of the disease when tumors are sufficiently large to be readily detected. While dormancy in primary tumors is best defined as the time between the carcinogenic transformation event and the onset of inexorable progressive growth, it can also occur as minimal residual or occult disease from treated tumors or as micro-metastases. The existence of dormant tumors has important implications for the early detection and treatment of cancer. Elucidating the regulatory machinery of these processes will be instrumental in identifying novel early cancer biomarkers and could provide a rationale for the development of dormancy-promoting tumor therapies. Despite the high prevalence of microscopic, dormant tumors in humans and the significant clinical implications of their early detection, this area in cancer research has, to date, been under investigated. In this mini review observations, models and experimental approaches to study tumor dormancy are summarized. Additionally, analogies and distinctions between the concepts of "tumor dormancy" and that of the "cellular dormancy" of tumor cells, as well as between the "exit from tumor dormancy" and the "onset of the angiogenic switch" are discussed. PMID- 20363067 TI - Re: Per-Anders Abrahamsson. Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature. Eur Urol 2010;57:49-59. PMID- 20363070 TI - Metabolic oxidative stress induced by a combination of 2-DG and 6-AN enhances radiation damage selectively in malignant cells via non-coordinated expression of antioxidant enzymes. AB - Our earlier studies have shown that simultaneous inhibition of glycolysis and pentose phosphate pathway using 2-deoxy-d-glucose (2-DG, an inhibitor of glycolysis) and 6-aminonicotinamide (6-AN, an inhibitor of pentose phosphate pathway) lead to metabolic oxidative stress (MOS), resulting in radiosensitization in malignant cells. Present study was carried out to investigate the effects of 2-DG and 6-AN on intricately regulated endogenous antioxidant defense against MOS during radiosensitization by this combination. Two human tumor cell lines {Head and Neck Squamous carcinoma (KB) and Glioma (BMG 1)} and one non-malignantly transformed cell line (human embryonic kidney, HEK) were used in this study. The presence of 2-DG and 6-AN (added just before irradiation) for 4h, significantly decreased the clonogenicity and metabolic viability of KB and BMG-1 cell lines, while no significant change was seen in HEK cells. Accumulation of ROS was observed only in malignant cell lines, which displayed a compromised redox status evident from enhanced NADP(+)/NADPH and GSSG/GSH ratios and a concomitant decrease in glutathione reductase level and activity at 24h following treatment. The levels and activities of Cu, Zn-SOD and Mn-SOD increased with MOS and were accompanied by a decreased GPx and unaltered catalase activity and level. These results suggest that non-coordinated expression of antioxidant defense, besides compromised redox status, led to selective radiosensitization in the malignant cells. PMID- 20363071 TI - Gold and gold-iron modified zeolites--towards the adsorptive deodourisation. AB - Zeolites exhibiting different structures (Y, Beta, and ZSM-5) were modified with gold and iron and applied for odour adsorption from the air containing dibutyl sulphide (Bu(2)S) used as a representative odour producing compound. The structure of the zeolites used determines the rate of adsorption (higher on Y type zeolites and smaller on two other zeolites), whereas hydrophilicity affects the selectivity towards Bu(2)S adsorption increasing in the order: Y0.999). CONCLUSIONS: CBZ and Lidocaine were effective for treating clustering seizures of CwG. We confirmed that the treatment period can be shortened without loss of efficacy. Therefore, we consider 1 day therapy with CBZ or Lidocaine to be sufficient. PMID- 20363084 TI - [How to quantify limb edema?]. AB - Edema of venous or lymphatic origin is frequently encountered in vasculopathies. Clinical diagnosis is readily made but precise quantification of edema is difficult. Various procedures have been proposed to quantify edema volume or analyze its composition. Water volumetry remains the gold standard but volumetry calculated with formulas from circumferential measurements for a cylinder or frustum methods are reproducible with high interrater and intrarater reliability. Automated measurement systems are expensive and reserved for research. Ideally, volume measurements for a given patient during the follow-up should be made by the same practitioner using the same method because the different methods are not interchangeable. Notably, edema composition can be evaluated by high frequency ultrasound, CT-scan, MRI or bioimpedance. Edema quantification is essential during patient follow-up and the method to be used depends on the objectives to be met. PMID- 20363085 TI - [Comparison of the automated oscillometric method with Doppler ultrasound method to access the Ankle-Brachial Pressure Index (ABPI)]. AB - OBJECTIVE: The Ankle-Brachial Pressure Index (ABPI) is the easiest non-invasive method for the assessment of peripheral arterial diseases (PAD) but remains uncommon in general practice, because of the need for training and specific devices. The purpose of this survey was to assess the reliability of the automated oscillometric measurement of the ABPI, compared with the gold-standard Doppler ultrasound measurement. METHODS: A study was conducted on patients aged 65 years and over without diagnosed PAD hospitalized in the Teaching Hospital of Angers (France) from July 2008 to March 2009. In compressive ankle arteries and atrial fibrillation were exclusion criteria. ABPI measurements were performed by the same examiner with oscillometric and Doppler devices. Reproducibility was assessed by the intra-class correlation coefficient of agreement (ICC) and the Bland-Altman method. RESULTS: Out of the 287 eligible hospitalized patients, 221 patients were included in the study and 56 (25%) had an ABPI below 0.90. The inter-method reliability is poor (ICC = 0.35+/-0.08) and the mean difference between the methods was 0.08+/-0.26 according to the Bland-Altman method. CONCLUSION: Automatic oscillometric devices cannot be recommended as a reliable alternative to access the ABPI. PMID- 20363086 TI - Changes in quantitative ultrasound in preterm and term infants during the first year of life. AB - Since most of in utero bone mass accretion occurs during the third trimester and postnatal need for bone nutrients is increased, preterm infants have an increased risk of low bone mass. Early identification of the risk is of crucial importance. Quantitative ultrasound, which is a relatively inexpensive, portable, noninvasive, and radiation-free method, gives information about bone density, cortical thickness, elasticity and microarchitecture. The aim of this study was to obtain quantitative ultrasound measurements of tibial speed of sound of preterm and term infants and to assess clinical factors associated with these measurements during the first year of life. Seventy-eight preterm and 48 term infants were enrolled in this study. Measurements were made on the 10th day of life in both groups, and were repeated on the 2nd, 6th and 12th months for preterm infants and on the 12th month for the term infants. Speed of sound on preterm infants was significantly decreased on the 2nd month but significantly increased on the 12th month (P=0.00). Comparing speed of sound of term and preterm infants, 10th day measurements were significantly different (P=0.00), but there was not any significant difference between the 12th month values (P=0.26). There was not any relation between biochemical parameters and speed of sound. The technique has potential clinical value for assessment of bone status. Further studies with long term follow up are needed to evaluate the value of quantitative ultrasound with other bone markers to predict the risk of fracture. PMID- 20363087 TI - Isolation and structure elucidation of an interaction product of aminotadalafil found in an illegal health food product. AB - An interaction product of aminotadalafil was isolated from an illegal health food product. The structure of the interaction product was elucidated by means of IR, NMR, and mass spectroscopy. The hitherto unknown compound was characterized as condensation product of aminotadalafil and hydroxymethylfuraldehyde and is probably the result of a drug-excipient incompatibility. PMID- 20363088 TI - Determination of topiramate in human plasma by capillary electrophoresis with indirect UV detection. AB - A rapid capillary zone electrophoresis method with indirect UV detection for the determination of topiramate in human plasma was developed and validated. The analyses were carried out with a background electrolyte composed of 10mM sulfamethoxazole as chromophore in phosphate buffer (25 mM, pH 12.0); gabapentin was selected as the internal standard. Application of a voltage of +15 kV led to an analysis time shorter than 5 min; indirect UV detection was operated at 256 nm. Isolation of topiramate from plasma was accomplished by a carefully implemented solid-phase extraction procedure on C18 cartridges. The method provided a linear response over the concentration range of 2-60 microg of topiramate per mL of plasma. The limit of detection (LOD) was 0.8 microg mL(-1) and the limit of quantitation (LOQ) was 2.0 microg mL(-1). Precision, expressed as relative standard deviation, was always lower than 7.3%, extraction yields were always greater than 92%. The results obtained analysing plasma samples from epileptic patients undergoing therapy with topiramate were satisfactory in terms of precision and selectivity. PMID- 20363090 TI - Extended-release naltrexone for treatment of alcohol dependence in primary care. AB - The feasibility of using extended-release injectable naltrexone (XR-NTX) to treat alcohol dependence in routine primary care settings is unknown. An open-label, observational cohort study evaluated 3-month treatment retention, patient satisfaction, and alcohol use among alcohol-dependent patients in two urban public hospital medical clinics. Adults seeking treatment were offered monthly medical management (MM) and three XR-NTX injections (380 mg, intramuscular). Physician-delivered MM emphasized alcohol abstinence, medication effects, and accessing mutual help and counseling resources. Seventy-two alcohol-dependent patients were enrolled; 90% (65 of 72) of eligible subjects received the first XR NTX injection; 75% (49 of 65) initiating treatment received the second XR-NTX injection; 62% (40 of 65), the third. Among the 56% (n = 40) receiving three injections, median drinks per day decreased from 4.1 (95% confidence interval = 2.9-6) at baseline to 0.5 (0-1.7) during Month 3. Extended-release naltrexone delivered in a primary care MM model appears a feasible and acceptable treatment for alcohol dependence. PMID- 20363091 TI - Posttraumatic stress disorder's role in integrated substance dependence and depression treatment outcomes. AB - Posttraumatic stress disorder (PTSD) frequently co-occurs with depression and substance use disorder (SUD). This study investigates the impact of PTSD diagnosis on treatment outcomes of 178 veterans treated for depression and SUD, with Integrated Cognitive-Behavioral Therapy (ICBT) or 12-Step Facilitation Therapy (TSF). Percentage days abstinent (PDA) and Hamilton Depression Rating Scale total score (HDRS total) trajectories were created. PDA was similar through initial follow-up; however, by 18 months, ICBT participants without PTSD had better PDA (M = 91%) than those without PTSD in TSF (M = 76%) and those with PTSD in either group (M = 75%-77%). Across time, participants with PTSD had higher depression levels than those without PTSD but benefited similarly from treatment (main effect, p < .004). Both conditions demonstrated reductions in average HDRS at 18 months (M = 17%-29%). Findings highlight the need to assess for PTSD and to investigate how to treat concomitant SUD, depression, and PTSD. PMID- 20363089 TI - Comparison of two intensities of tobacco dependence counseling in schizophrenia and schizoaffective disorder. AB - Compared to the general population, smokers with schizophrenia (SCZ) have reduced success in quitting smoking with usual approaches. This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia (TANS) or Medication Management (MM)-for smokers who were motivated to quit. Individual counseling sessions were provided by mental health clinicians in mental health settings, along with nicotine patch. The two treatments varied in intensity and frequency of sessions. Eighty-seven subjects were randomized and attended at least one treatment session. Twenty-one percent (n = 18) of participants had continuous abstinence at 12 weeks after the target quit date, which was not significantly different between conditions (15.6% TANS vs. 26.2% MM, chi(2) = 1.50, p = .221). Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide. Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence. PMID- 20363092 TI - Smoking outcome by psychiatric history after behavioral and varenicline treatment. AB - Treatment outcomes were compared across smokers enrolled in the COMPASS cessation trial with (positive psychiatric history [PH+], n = 271) and without (PH-, n = 271) a diagnosis of PH based on medical record evidence of anxiety, depression, psychotic disorder, or bipolar disorder. Everyone received behavioral counseling plus varenicline and was followed for 6 months post quit date. PH+ smokers took varenicline for fewer days on average (59.4 vs. 68.5, p < or = .01) but did not differ in their use of behavioral treatment. PH+ smokers were more likely to report anxiety and depression, but side-effect intensity ratings did not differ after adjusting for multiple comparisons. Overall, all side effects were rated as moderate intensity or less. Groups had similar 30-day abstinence rates at 6 months (31.5% PH+ vs. 35.4% PH-, p = .35). In sum, having a psychiatric diagnosis in this trial did not predict worse treatment outcome or worse treatment side effects. PMID- 20363094 TI - Cost analysis of the combined procedure of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). AB - AIM: The aim of the present study was to address the economic cost of the innovative comprehensive approach involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal surface malignancies, and to compare it with the financial support received by our centre. METHODS: A retrospective economic analysis was carried out on 382 consecutive procedures performed at a tertiary referral centre during the period 1995-2008. The costs of the combined therapy were estimated using the activity based costing methodology. The financial support was assessed according to the current diagnosis-related group classification and reimbursement rates. RESULTS: The mean cost for one hospital stay was euro36,015.89 (range 28,435.24 82,189.08); mean length of stay was 24.3 days (range 9-108). In counterpart, our hospital received a total financial support of euro804,483.30, resulting in a deficit of euro1861,301.99 for the two years. CONCLUSION: The Italian current diagnosis-related groups classification does not include cytoreduction and HIPEC. This results in a relevant economic deficit for the hospitals offering this treatment option to their patients and a slow diffusion of the technique in our country. Two corrective measures are needed: to include this procedure in the official list of medical acts, and to determine its specific cost for reimbursing. PMID- 20363095 TI - [Leg ischaemia due to thrombosis of femoral arterial catheter]. PMID- 20363096 TI - Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. AB - CONTEXT: MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate the gene expressions at the posttranscriptional level, subsequently control crucial physiological processes. Recent evidence demonstrates that some miRNAs have the functions similar to oncogene or tumor suppressors, it may play important roles in tumorigenesis. MiRNA expression profiles may become useful biomarkers for cancer diagnostics, prognosis and prediction of response to treatment, and it could be a powerful tool for cancer prevention and therapeutics. OBJECTIVE: To explore the global expression profile of miRNAs in non small cell lung cancer (NSCLC) and its potential relevance to clinicopathological characteristics and prognosis. METHODS: LNA microRNA microarrays were utilized to detect miRNA expression levels in eight surgically removed lung carcinoma tissues (LCT) and their corresponding normal lung tissues (NT). After initial microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR), miR-21, miR-143 and miR 181a were selected for further study in another 47 paired LCTs and matched NTs by qRT-PCR using Taqman microRNA assay. RESULTS: Twenty-seven microRNAs were observed to be deregulated greater than two-fold in LCT compared with NT by microarray. Consistenting with the microarray, the expression level of miR-21 by qRT-PCR was significantly higher in tumor tissues than in adjacent normal tissues (P=0.026); while miR-143 (P=0.000) and miR-181a (P=0.000) were downregulated in LCT. Interestingly, among the 47 NSCLC cases, low level expression of miR-143 was significantly correlated with smoking status (P=0.026), high miR-21 expression (hazard ratio, 5.993; 95% confidence interval, 2.518-14.264; P=0.000) and low miR 181a expression (hazard ratio, 0.328; 95% confidence interval 0.142-0.756; P=0.009) were associated with poor survival, independent of clinical covariates, including TNM staging, lymph note status. CONCLUSION: Our data thus indicating the potential of miR-21, miR-143 and miR-181a as a novel diagnostic or prognostic biomarker for NSCLC. Besides, these data will guide further studies of specific microRNAs might become potential targets for therapeutic intervention. PMID- 20363097 TI - [From insomnia to restless legs syndrome]. PMID- 20363098 TI - [Restless legs syndrome in children and adolescents]. AB - Restless legs syndrome (RLS) is imperfectly described in child and adolescent. As in adult, RLS is also an uncomfortable and irresistible urge to move his or her legs, usually happens at bedtime but can occur at other times, when the legs have been inactive, such as when sitting still for a long period of time. Unfortunately, there is no specific test for RLS in children or adolescents. Diagnosis is made based on clinical symptoms. A medical history and complete physical exam is conducted to rule out any other possible health problems. An overnight sleep study may be recommended to evaluate for other sleep disorders, especially periodic limb movement disorder. A relationship with Attention Deficit Disorder Hyperactivity is common, and treatment options claim to be studied, and moreover in both conditions. PMID- 20363099 TI - Long-term cardiovascular outcome after elective abdominal aortic aneurysm open repair. AB - BACKGROUND: We analyzed the incidence of late cardiovascular events and mortality after elective infra-/juxtarenal abdominal aortic aneurysm open repair (AAA-OR). METHODS: We included patients who survived AAA-OR in our center in 1988-2006. We registered late cardiac, cerebrovascular, and peripheral vascular events, as well as all-cause and cardiovascular mortality. We calculated patient survival and freedom from cardiovascular events (Kaplan-Meier) and evaluated risk factors (multivariate analysis). RESULTS: We studied 297 patients: 292 (98.3%) men, aged 67 +/- 7 (44-83) years, 143 (48.1%) bifurcated grafts. In a mean follow-up of 78.7 +/- 52.9 months, we registered 203 cardiovascular events in 123 (41.4%) patients, at a rate of 0.16 cardiovascular events/patient-year. Eleven (3.7%) patients suffered graft-related complications. Freedom from cardiovascular events was 94.2%, 67.2%, 45.7%, and 27.6% at 1, 5, 10, and 15 years, respectively. Survival was 96.6%, 74.7%, 50.7%, and 31.5%, respectively. The main cause of death was cardiovascular disease (n = 54, 18.2%), followed by cancer (n = 43, 14.5%). Only four (1.3%) deaths were graft-related. Coronary artery disease and chronic renal failure were predictive of cardiovascular mortality (p = 0.033 and 0.006). CONCLUSION: Although long-term survival is similar to that in the general population, successful AAA-OR patients remain at increased risk of cardiovascular events throughout their lifetime. Graft-related complications are rare, confirming the durability of the procedure. PMID- 20363100 TI - The external jugular vein: an alternative outflow for insertion of upper extremity arteriovenous grafts in patients with obstructed axillary vein. PMID- 20363101 TI - A functional murine model of hindlimb demand ischemia. AB - BACKGROUND: To date, murine models of treadmill exercise have been used to study general exercise physiology and angiogenesis in ischemic hindlimbs. The purpose of these experiments was to develop a murine model of demand ischemia in an ischemic limb to mimic claudication in humans. The primary goal was to determine whether treadmill exercise reflected a hemodynamic picture which might be consistent with the hyperemic response observed in humans. METHODS: Aged hypercholesterolemic ApoE null mice (ApoE(-/-), n = 13) were subjected to femoral artery ligation (FAL) and allowed to recover from the acute ischemic response. Peripheral perfusion of the hindlimbs at rest was determined by serial evaluation using laser Doppler imaging (LDI) on days 0, 7, and 14 following FAL. During the experiments, mice were also assessed on an established five-point clinical ischemic score, which assessed the degree of digital amputation, necrosis, and cyanosis compared to the nonischemic contralateral limb. After stabilization of the LDI ratio (ischemic limb flux/contralateral nonischemic limb flux) and clinical ischemic score, mice underwent 2 days of treadmill training (10 min at 10 m/min, incline of 10 degrees ) followed by 60 min of daily treadmill exercise (13 m/min, incline of 10 degrees ) through day 25. An evaluation of preexercise and postexercise perfusion using LDI was performed on two separate occasions following the onset of daily exercise. During the immediate 15 min postexercise evaluation, LDI scanning was obtained in quadruplicate, to allow identification of peak flux ratios. Statistical analysis included unpaired t-tests and analysis of variance. RESULTS: After FAL, the LDI flux ratio reached a nadir between days 1 and 2, then stabilized by day 14 and remained stable through day 25. The clinical ischemic score stabilized at day 7 and remained stable throughout the rest of the experiment. Based on stabilization of both the clinical ischemic score and LDI ratio, exercise training began on day 15. The peak 15 min postexercise LDI ratio increased significantly compared to the preexercise ratio on day 17 (0.48 +/- 0.04 vs. 0.34 +/- 0.04, p < 0.05) and day 25 (0.37 +/- 0.03 vs. 0.27 +/- 0.03, p < 0.01). Within 2 hr of exercise, the LDI ratio returned to preexercise levels on both days 17 and 25. CONCLUSION: Clinical and hemodynamic stabilization of limb perfusion is evident by 14 days after FAL. FAL followed by demand ischemia results in a reversible relative hyperemic response similar to that observed in exercising human claudicants. A murine model of FAL associated with demand ischemia may be useful to evaluate the metabolic, inflammatory, and flow-related changes associated with claudication in humans. PMID- 20363102 TI - Sticky platelet syndrome: an unusual presentation of arterial ischemia. AB - A 48-year-old woman presented with bilateral lower extremity critical limb ischemia. In addition to this, her work-up revealed multiple other thromboembolic insults including cerebral and visceral emboli. Initial laboratory findings were significant for an indeterminate platelet count, secondary to platelet clumping. After appropriate emergent surgical treatment including bilateral lower extremity embolectomy, the patient was empirically anticoagulated with a direct thrombin inhibitor. Further embolic work-up discovered bilateral renal and splenic infarctions as well as a large mobile mitral vegetation. Finally, an upper extremity duplex revealed left axillary, left subclavian, and right internal jugular acute deep vein thromboses. Mitral valve replacement was performed to remove the septic source. A series of hypercoagulability studies was done, and results were positive for lupus anticoagulants. Months after her recovery, the patient was tested and found to be positive for sticky platelet syndrome. PMID- 20363103 TI - Changes in red blood cell transfusion practice during the turn of the millennium: a retrospective analysis of adult patients undergoing elective open abdominal aortic aneurysm repair using the Mayo database. AB - BACKGROUND: Significant changes in perioperative red blood cell (RBC) transfusion practice during the past two decades have been reported but similar data are not available for patients undergoing abdominal aortic aneurysm (AAA) surgery. METHODS: Adult patients who had undergone primary, elective, open AAA repair were stratified into one of two transfusion-related groups: early practice (1980-1982) or late practice (2003-2006). RBC transfusion and hemoglobin concentration (Hb) were analyzed as a continuous variable and compared between groups with use of the rank sum test. Perioperative complications were compared between groups with Fisher's exact test. Data were age adjusted, and analyses were corrected for multiple comparisons. RESULTS: Compared with the early practice group, patients in the late practice group had significantly lower intraoperative (mean 10 +/- 1.4 vs. 11.5 +/- 1.5 g/dL), postoperative (11.9 +/- 1.4 vs. 13.4 +/- 1.5 g/dL), and discharge Hbs (mean 10.8 +/- 1.2 vs. 12.5 +/- 1.5 g/dL) (p < 0.0001 for each variable). Patients in the late practice group were significantly less likely to receive intraoperative allogenic transfusions (46% vs. 99%, p < 0.0001). Additionally, significantly fewer total allogenic units of RBCs per patient were transfused in the late practice group (mean 1.7 vs. 4.3, p < 0.0001). Intraoperative autotransfusions were used in 97% of the late practice patients but in none of the early practice patients (p < 0.0001). In the late practice group, 119 patients (40%) experienced a major perioperative morbidity or mortality event compared with 106 patients (35%) in the early practice group (p = 0.27). CONCLUSION: In this retrospective analysis, we observed significantly lower perioperative Hb, fewer allogenic RBC transfusions, and more autotransfusions in open AAA repairs done in 2003-2006 versus those done in 1980 1982. Additionally, late transfusion practice patients were older and had more comorbid diseases. Despite these observations, no significant differences in perioperative morbidity or mortality were observed between groups. PMID- 20363105 TI - Celiac artery aneurysms. AB - Celiac artery aneurysms are extremely rare vascular lesions that are frequently asymptomatic. When present, clinical manifestations are often vague and unspecific. The most serious complication of celiac artery aneurysms is rupture with a mortality rate up to 100%. Elective surgical repair, with a mortality rate of 5%, is recommended except when operative risks contraindicate abdominal surgery. The authors present three clinical cases of celiac artery aneurysms treated by open surgery and discuss the surgical options adopted. PMID- 20363104 TI - Neutrophil gelatinase associated lipocalin as a biomarker for acute kidney injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. AB - BACKGROUND: Acute kidney injury (AKI) is a significant cause of morbidity and mortality following cardiac surgery throughout the world. The paucity of early biomarkers has hampered early therapeutic intervention. Our aim was to evaluate plasma neutrophil gelatinase associated lipocalin (NGAL) levels as a predictor of renal injury in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) along with markers of oxidative stress. METHODS: About 30 patients undergoing CABG with CPB were prospectively studied. Blood was collected before bypass, at 4, 12, and 24 hr after CPB initiation, for the analysis of NGAL and oxidative stress markers. RESULTS: Eight of 30 patients (26.6%) developed AKI, while 22 (73.4%) did not, as measured by serum creatinine, after 48-72 hr of surgery. However, plasma NGAL levels at 4 hr were high in patients who developed AKI compared with those who did not (352.97 +/- 49.32 vs. 199.83 +/- 23.28 ng/mL, p = 0.000). There was a significant difference in aortic cross-clamp time (p = 0.000), duration of CPB (p = 0.000), and ventilation duration (p < 0.05) between the two groups. The level of malondialdehyde (MDA), a marker of oxidative stress, was higher only at 4 hr in the AKI group. No significant differences were observed in the level of antioxidants between the two groups. A significant correlation was found between plasma NGAL at 4 hr and the change in serum creatinine (r = 0.863, p = 0.006) as well as ventilation duration (r = 0.830, p = 0.011). The sensitivity and specificity of plasma NGAL at 4 hr after CPB was optimal at the 229 ng/mL cut-off with an area under the curve of 0.98 for prediction of AKI. CONCLUSION: Measurement of plasma NGAL in patients in the first few hours after CPB is predictive of AKI. Oxidative stress as measured by the level of MDA and antioxidants has no substantial role in the progression of AKI during CABG with CPB. PMID- 20363106 TI - Endovascular therapy of ascending thoracic aorta. AB - We describe the endovascular treatment given to a patient who, after surgery on the ascending thoracic aorta due to acute type A dissection (Bentall's procedure), developed a pseudoaneurysm 12 cm in diameter of the ascending aorta at the brachiocephalic trunk. Firstly, an extra-anatomical carotid-carotid bypass was performed, which was followed by endovascular treatment, excluding the aortic arch from the origin of both coronary arteries to the origin of the left common carotid artery, occluding the brachiocephalic trunk. For accurate placement of the endoprosthesis, the device was released after cardiac arrest with adenosine. PMID- 20363107 TI - Intravascular ultrasound-guided true lumen reentry device for recanalization of unilateral chronic total occlusion of iliac arteries: technique and follow-up. AB - BACKGROUND: Endovascular revascularization of chronic total occlusion (CTO) of the iliac arteries is rapidly becoming first-line treatment, with surgical aortofemoral bypass procedures reserved for failure of endovascular treatment. Percutaneous subintimal recanalization is the most common endovascular revascularization technique for CTO of the iliac arteries. The primary reason for failure of the subintimal recanalization technique is failure to reenter the true lumen. This report describes the benefits of using true lumen reentry devices to improve the success and safety of conventional subintimal recanalization for revascularization of CTO of the iliac arteries. METHODS: This is a retrospective review of 11 patients with CTO of the iliac arteries in whom true lumen reentry was not successful using conventional subintimal recanalization. An intravascular ultrasound (IVUS)-guided true lumen reentry device was used in all patients to assist true lumen reentry. Clinical records, procedural records, angiographic imaging, and follow-up data were analyzed. Indications for intervention, length and location of the lesion treated, access site(s), location of true lumen reentry, stent use, procedural times, technical success, and complications were analyzed in all patients. RESULTS: The technical success of true lumen reentry at the desired point was 100%. Total procedure time from the start of reentry device manipulation to achieve reentry was <10 min (routinely <5 min). Mean patient follow-up was 10.5 months. At follow-up, all patients had palpable femoral pulses. The ankle-brachial index normalized (>0.9) in six patients and improved significantly in the remaining five patients. Rest pain resolved and claudication improved in all patients. Out of seven patients who had foot ulcers, the ulcers healed completely in five and demonstrated improved healing in two, with the clinical manifestation of osteomyelitis resolved in two. No procedure-related complications were noted. The amputation-free survival was 100%. CONCLUSION: True lumen reentry devices greatly improve the technical success and safety of percutaneous recanalization procedures in CTO of the iliac arteries. There are significant reductions in procedure time and complication rates associated with the use of these devices. PMID- 20363108 TI - Routine versus selective use of intraoperative angiography during thromboembolectomy for acute lower limb ischemia: analysis of outcomes. AB - BACKGROUND: The success of thromboembolectomy for acute lower limb ischemia depends on the complete removal of all thromboembolic material accessible to the Fogarty catheter. Intraoperative arteriography can be used during arterial thromboembolectomy as a guide for extension of procedure to ensure complete clearance of the arterial tree and distal patency. However, it is still matter of debate if intraoperative angiography should be routinely performed in all cases or only in selected cases, depending on intraoperative findings, when the surgeon suspects an incomplete desobstruction. METHODS: Details of 380 thromboembolectomies in 361 patients with acute lower limb ischemia due to native vessel occlusion were prospectively recorded over a 12-year period in a central hospital vascular unit setting. The relevance of intraoperative angiography was retrospectively analyzed. The procedures were divided into two groups: group A, when intraoperative angiography was performed in selected cases (selective angiography), and group B, when angiography was performed as a routine procedure in all cases (routine angiography). Thrombectomy and embolectomy cases were separately analyzed. RESULTS: "On-table" angiography was used in 57 (26.4%) of 216 cases in group A and in all 164 cases (100%) of group B. Included in this study were 225 embolectomies and 155 thrombectomies of native vessels. After thrombectomy, the adoption of routine intraoperative angiography (group B) resulted in a statistically significant higher intraoperative reintervention rate than did selective intraoperative angiography (group A) (53.4% vs. 29.9%; p < 0.05). Also, after embolectomy extension of procedure, the rate was higher in group B than in group A (17% vs. 9.2%), but it did not reach statistical significance (p > 0.05). Considering the overall casuistic, at 24 months after thromboembolectomy, group B resulted in a lower incidence of reocclusion in comparison with group A (p < 0.05), whereas there was no statistical difference between the two groups in terms of amputation (p > 0.05) or of mortality (p > 0.05). Considering separately patients treated by embolectomy and by thrombectomy, reocclusion rate at 24 months was lower in group B than in group A, after thrombectomy and after embolectomy, with a statistical significance (p < 0.05). Amputation rate at 24 months was similar in group A and group B after embolectomy (10.7% vs. 8.9%; p > 0.05). After thrombectomy, there was in group B a slight advantage in comparison with group A, although not reaching statistical significance (31.3% vs. 46.2%; p > 0.05). There was no difference in mortality rate according to treatment group. CONCLUSION: Routine use of intraoperative angiography influences outcome after thromboembolectomy for lower limb acute arterial occlusion. Routine use of intraoperative angiography, compared with selective use, results in higher rate of extension of the procedure for residual lesion and in a lower reocclusion rate at 24 months. PMID- 20363109 TI - Rasch calibration of physical activity self-efficacy and social support scale for persons with intellectual disabilities. AB - The purpose of this study was to investigate the construct validity of the Self Efficacy/Social Support for Activity for persons with Intellectual Disability (SE/SS-AID) scales developed by Peterson, Peterson, Lowe, & Nothwehr (2009). A total of 146 participants with intellectual disabilities completed 6 self efficacy (SE) items and 18 social support (SS) items. After applying the Rasch rating model, all SE items and 17 SS items fit the model and measured a single construct. Thus, it was able to determine the item difficulty and person's level of SE and SS for physical activity by calculated logit scores. No items showed evidence for differential functioning by the level of intellectual disability. Model fit of SS subscales (e.g., staff, family, and peer) showed good-fit as well. In conclusion, SE and SS scales for physical activity can be measured more accurately for persons with intellectual disabilities by using the modified scales validated in this study. PMID- 20363110 TI - Pain after palliative radiotherapy for spine metastases. AB - AIMS: The purpose of the study was to evaluate the response to palliative radiotherapy in patients with painful spinal metastatic disease (SMD). MATERIALS AND METHODS: Three hundred and fifty-five patients admitted to the Norwegian Radium Hospital for radiotherapy for painful SMD were included in a prospective study and were followed up 2 months later. The Brief Pain Inventory was used to assess pain. Analgesic consumption was recalculated into the daily oral morphine equivalent dose. The radiotherapy-related response rates were calculated using the criteria of the International Bone Metastases Consensus Group (IBMCG), taking into account the use of concomitant analgesics. The response to radiotherapy was assessed as complete or partial and non-response as stable pain, pain progression or 'other'. RESULTS: Brief Pain Inventory forms were obtained at follow-up from 229 of the 355 patients. Two months after radiotherapy, the median self-reported worst pain decreased significantly, but the median oral morphine-equivalent dose increased from 40 to 60 mg (P<0.001). Forty-three per cent of the patients reported pain relief, but a radiotherapy-related response was found in 37% of the patients. Overall correspondence between the patients' self-reported changes in pain experience and the IBMCG-based response categories was obtained in 63% of the patients. CONCLUSIONS: The radiotherapy-related response rates in our study were lower than those reported previously in patients with bone metastases in general, which possibly indicates the presence of more complex pathophysiological mechanisms of pain in SMD. PMID- 20363111 TI - Radiotherapy research priorities for the UK. PMID- 20363112 TI - Web-based virtual microscopy at the RWTH Aachen University: didactic concept, methods and analysis of acceptance by the students. AB - Fundamental knowledge of microscopic anatomy and pathology has always been an essential part in medical education. The traditional didactic concept comprises theoretical and practical lessons using a light microscope and glass slides. High speed Internet connections and technical improvement in whole-slide digital microscopy (commonly termed "virtual microscopy") provide a new and attractive approach for both teachers and students. High picture quality and unlimited temporal and spatial availability of histology samples from different fields are key advantages of web-based digital microscopy. In this report we discuss the technical requirements, system efficiency, optical resolution and didactic concept. Furthermore, we present a review of the experience gained in the course of one year based on an analysis of student acceptance. Three groups with a total of 192 students between the 3rd and 5th year of medical studies attending the practical courses of general and advanced histopathology had access to both glass mounted and digitalized slides. Prior to exams, students were asked to answer an anonymous questionnaire. The results of the study reflect the high acceptance and intensive use of the web-based digital histology by students, thus encouraging the development of further Web-based learning strategies for the teaching of histology and pathology. PMID- 20363113 TI - Therapeutic effect of norisoboldine, an alkaloid isolated from Radix Linderae, on collagen-induced arthritis in mice. AB - The alkaloid fraction of Radix Linderae, the main active component of this herb drug, has been proven to exhibit anti-inflammatory, analgesic and antimicrobial activities. The present study was undertaken to investigate the therapeutic potential of norisoboldine, the major isoquinoline alkaloid present in Radix Linderae, in collagen II -induced arthritis (CIA) of mice as well as the possible mechanisms. CIA was induced in mice by immunization with chicken type II collagen (II). After boosted on day 21, mice were treated with norisoboldine (10, 20, 40 mg/kg) for twenty consecutive days. The clinical scores, body weight changes and joint histopathology were evaluated. Norisoboldine treatment significantly alleviated the severity of the disease, based on the reduced clinical scores and elevated the lowered body weights of model mice. Meanwhile, this alkaloid dose dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and protected joint from destruction. Additionally, the serum level of anti-CII IgG and the CII-stimulated lymphocyte proliferation were remarkably decreased in the groups administered with norisoboldine. An assessment of Th1 function using the delayed-type hypersensitivity model confirmed that norisoboldine also significantly suppressed the enhanced T cell responses in vivo. These findings suggest that norisoboldine might be a potential therapeutic agent for rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses. PMID- 20363114 TI - Anti-inflammatory principles from Heritiera littoralis bark. AB - Compounds from the hexane, dichloromethane and acetone extracts of Heritiera littoralis bark were investigated for their nitric oxide (NO) inhibitory effects using RAW264.7 macrophage cells. The result indicated that ergosterol peroxide (13) exhibited the highest activity against NO release with an IC(50) value of 2.5 microM, followed by 6-alpha-hydroxystigmast-4-en-3-one (11, IC(50)=9.5 microM) and stigmast-4-en-3-one (9, IC(50)=15.9 microM), whereas other compounds showed moderate and mild effects (25.4- > 100 microM). Ergosterol peroxide (13) and 6-alpha-hydroxystigmast-4-en-3-one (11) were also tested against prostaglandin E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha) releases. It was found that ergosterol peroxide (13) possessed marked activity against PGE(2) release with an IC(50) value of 28.7 microM, while 6-alpha-hydroxystigmast 4-en-3-one (11) was 86.7 microM. However, these two compounds were inactive towards TNF-alpha release (IC(50) > 100 microM). The mechanism in transcriptional level of ergosterol peroxide (13) was found to down regulate mRNA expressions of iNOS and COX-2 in dose-dependent manners. PMID- 20363115 TI - Fatty acids and breast cancer: the role of stem cells. AB - Studies with animal models in vivo as well as with animal and human tumor cells in vitro suggest that specific fatty acids could reduce breast tumorigenesis. The most striking dietary fatty acid studies in animal models that show promise for reduction of breast cancer risk in humans are with conjugated linoleic acids (CLA) and n-3 fatty acids. Although a number of mechanisms have been proposed, the specific target of those fatty acids is not yet known. We sought to determine whether the effects of those fatty acids on terminally differentiated tumor cell seen could be due to alteration of breast cancer stem cells. The isomers, cis9, trans11-CLA and trans10, cis12-CLA, and the n-3 fatty acids, docosahexaenoic and eicosapentaenoic, reduced the proliferation of, and had increased toxicity towards, mammary tumor initiating cells. One mechanism involved in the effect of n-3 fatty acids may be due to alteration of the profile of prostaglandins. These results indicate that select fatty acids may be useful for preventing or reducing the risk of breast cancer as they may target the tumor initiating cell. PMID- 20363116 TI - Fatty acid oxidation and isoprostanes: oxidative strain and oxidative stress. AB - Oxidative stress is implicated as one of the key causes underlying many diseases. Free radicals are important constituents of basal physiology. Assessment of free radicals or the end products of their action has proved to be difficult. Consequently, authentication of the contribution of free radicals to physiology and pathology has usually been equivocal. Isoprostanes are biosynthesized in vivo, predominantly through free radical attack on arachidonic acid and are now regarded as robust biomarkers of oxidative stress in vivo. Isoprostanes are associated with many human diseases, and their concentration is altered over the course of normal human pregnancy, but their (patho)physiological roles have not yet been clearly defined. Measurement of F(2)-isoprostanes in body fluids could offer a unique analytical opportunity to study the role of free radicals in physiology and pathophysiology in order to comprehend both oxidative strain and oxidative stress. PMID- 20363117 TI - Mild asthma in overweight women: A new phenotype? AB - BACKGROUND: Epidemics of asthma and overweight have been linked recently. They might be associated with systemic inflammation. In asthma hyperresponsiveness to adenosine (AMP) is more closely related to inflammation than to methacholine (MCh). The aim of the study was to determine responsiveness to AMP and MCh in overweight compared with normal weight asthmatics. METHODS: Thirty women were enrolled (19 overweight) with mild controlled asthma according to GINA. A Body Mass Index (BMI) less than 25kg/m(2) was considered as normal and a BMI above 25kg/m(2) as overweight. We assessed the recent control of asthma (ACQ), pulmonary function tests, bronchial responsiveness to MCh and AMP (PC(20) and O'Connor two-point dose-response slope), perception of symptoms (Borg scale), and blood inflammatory markers (leptin and hs-CRP by ELISA). RESULTS: Overweight had a significant lower dose-response slope of the MCh challenge (p=0.009) as compared to normal weight patients, whereas no significant difference was observed for AMP challenge (p=0.27). Overweight patients had higher intercepts of the Borg scale measured before the MCh and AMP challenge tests (p=0.01 and p=0.03). Plasma leptin (p=0.001) and hs-CRP (p=0.05) concentrations were higher in overweight than normal weight patients. There was no correlation between challenges and inflammatory markers. CONCLUSIONS: Overweight asthmatic women have more pronounced systemic inflammation, but are less responsive to MCh. AMP responsiveness appeared to be comparable between both groups. Our findings suggest that overweight asthmatic women do not feature increased airway inflammation, but do represent a distinct phenotype as compared to normal weight patients. PMID- 20363119 TI - Effect of temperature on intracellular phosphorus absorption and extra-cellular phosphorus removal in EBPR process. AB - This study investigated the temperature influence on intracellular absorption and extra-cellular phosphorus removal by extra-cellular polymeric substance (EPS) in enhanced biological phosphorus removal (EBPR) process. Three sequencing batch reactors (SBRs) were operated in anaerobic/aerobic sequence at 5.0, 15.0 and 25.0 degrees C. Phosphorus removed by intracellular absorption was demonstrated as the dominant part (>80%) in total phosphorus removal operated under different temperatures and the highest total phosphorus removal rate of 95% was obtained due to the highest intracellular phosphorus absorption of 18.2mg P in a typical cycle at 15.0 degrees C. Phosphorus removed by EPS removal achieved the highest value at 5.0 degrees C (2.4 mg P/cycle), which resulted in a higher total phosphorus removal rate at 5.0 degrees C (90%) than that at 25.0 degrees C (83%). Low temperature was propitious to EPS phosphorus removal, accounting for 13% of total phosphorus removal at 5.0 degrees C, which could be mainly due to magnesium phosphate precipitation. PMID- 20363118 TI - Multiple faces of the SAGA complex. AB - The SAGA complex provides a paradigm for multisubunit histone modifying complexes. Although first characterized as a histone acetyltransferase, because of the Gcn5 subunit, SAGA is now known to contain a second activity, a histone deubiquitinase, as well as subunits important for interactions with transcriptional activators and the general transcription machinery. The functions of SAGA in transcriptional activation are well-established in Saccharomyces cerevisiae. Recent studies in S. pombe, Drosophila, and mammalian systems reveal that SAGA also has important roles in transcript elongation, the regulation of protein stability, and telomere maintenance. These functions are essential for normal embryo development in flies and mice, and mutations or altered expression of SAGA subunits correlate with neurological disease and aggressive cancers in humans. PMID- 20363120 TI - Solid-state cultivation of Trichoderma harzianum NBRI-1055 for modulating natural antioxidants in soybean seed matrix. AB - Trichoderma harzianum NBRI-1055 was used, as fungal candidate to enhance the antioxidant activities of soybean matrix by modulating polyphenolic substances during solid-state fermentation. Trichoderma-fermented soybean (TFS) and unfermented soybean (UFS) products were extracted with water (W) and methanol (M). Total phenolic content of TFS-W and TFS-M extracts were significantly higher than that of UFS-W and UFS-M extracts. The effectiveness of extracts for total flavonoid content, antioxidant activity, free radical scavenging activity, reducing power, lipid peroxidation, metal ions-chelation, hydroxyl and superoxide radicals scavenging properties in descending order was TSF-W>TSF-M>USF-M>UFS-W. TFS extracts demonstrated significant protection against oxidative DNA and protein damages caused by hydroxyl radicals. For the specific phenolics profile, HPLC analysis was performed, which showed that the TFS extracts were also higher in isoflavones, flavonoids and phenolic acids, suggesting that this strategy may help to enhance TFS as potential antioxidants for use in preparation of soy food products. PMID- 20363121 TI - In situ modification of bacterial cellulose network structure by adding interfering substances during fermentation. AB - In an attempt to obtain bacterial cellulose (BC) with improved rehydration ability, Tween 80, urea, fluorescent brightener, hydroxypropylmethyl cellulose (HPMC) and carboxymethyl cellulose (CMC) were introduced into BC fermentation medium. Measurements of the mechanical strength of the resulting BCs (TBC, UBC, FBC, HBC and CBC) showed a decline except for UBC. SEM images showed that, although the cellulose bundle widths of FBC, HBC and CBC increase, the cellulose network void in FBC grew, while those in HBC and CBC shrank. X-ray diffraction and FT-IR analysis demonstrated that the addition of HPMC and CMC reduced the degree of crystallinity in their corresponding MBCs from 70.54% to 52.23% and 45.38%, respectively. HBC and CBC also exhibited the highest rehydration ability among all MBCs as well as the lowest crystallinity. The in situ modification with HPMC and CMC during fermentation can effectively improve rehydration ability of BC by altering its network structure. PMID- 20363122 TI - Alum sludge-based constructed wetland system for enhanced removal of P and OM from wastewater: concept, design and performance analysis. AB - The concept, design and performance analysis of a four-stage novel constructed wetland system (CWs) capable of enhanced and simultaneous removal of phosphorus (P) and organic matter (OM) from wastewaters is described. Alum sludge, a largely available by-product of drinking water facilities using aluminium salts as coagulant was used as the media. Under a hydraulic loading rate of 1.27 m(3)/m(2) d and a range of organic loading rate of 279.4-774.7 g-BOD(5)/m(2)d and 361.1 1028.7 g-COD/m(2)d, average removal efficiencies (mean+/-SD) of 90.6+/-7.5% for BOD(5) and 71.8+/-10.2% for COD were achieved, respectively. P removal was exceptional with average removal efficiency of 97.6+/-1.9% achieved for soluble reactive P at a mean influent concentration of 21.0+/-2.9 mg/l. Overall, the system holds great promise as a novel CWs for simultaneous removal of P and OM, and at the same time, it transforms alum sludge from a waste into a useful material. PMID- 20363123 TI - Preparation of cross-linked aggregates of aminoacylase from Aspergillus melleus by using bovine serum albumin as an inert additive. AB - The effects of bovine serum albumin (BSA) addition on the cross-linked enzyme aggregates (CLEA) of aminoacylase from Aspergillus melleus (EC 3.5.1.14) were conducted at varying glutaraldehyde to enzyme ratio. After optimization, CLEA of aminoacylase prepared with 10 mg BSA per 100 mg enzyme retained 82% activity recovery (named CLEA-E-BSA) whereas CLEA prepared without BSA retained only 24% activity recovery (named CLEA-E) due to the low content of amine residues of aminoacylase. Compared with free aminoacylase, the catalytic performance of CLEA E-BSA (k(cat)/K(m)) decreased from 0.357 to 0.270, while the thermal stability of CLEA-E-BSA has improved considerably, maintaining 52% residual activity after 24h of incubation at 47 degrees C whereas the free enzyme was almost inactivated. Additionally, the inactive curve of CLEA-E-BSA fitted a two-exponential deactivation model. The reusability of CLEA-E-BSA with respect to N-acetyl-DL methionine hydrolysis was evaluated. CLEA-E-BSA showed 82.4% residual activity even after 10 cycles of repeated use. PMID- 20363124 TI - Structure of Agaricus spp. fucogalactans and their anti-inflammatory and antinociceptive properties. AB - Fucogalactans from Agaricus brasiliensis (EPF-Ab) and A. bisporus var. hortensis (EPF-Ah) were prepared via by aqueous extraction and a purification procedure. EPF-Ab had M(w) 19.4 x 10(3)g/mol and EPF-Ah M(w) 31.1 x 10(3)g/mol. EPF-Ab had a (1-->6)-linked alpha-D-Galp main-chain partially substituted in O-2 by non reducing end-units of alpha-L-Fucp. EPF-Ah had a similar main-chain with O-2 substitution, but was partially methylated at HO-3, as well as having 2.5% non reducing end-units of beta-D-Gal. In mice, EPF-Ab gave 39% antinociceptive inhibition (ID(50)>100mg/kg) and no anti-inflammatory activity. EPF-Ah also gave an inhibition of 39% at ID(50) 0.33 mg/kg and also inhibited by 61% (ID(50) 5.0mg/kg) total cell migration and by 32% peritoneal capillary permeability, which is related to the anti-inflammatory effect. The small differences in chemical structure in these polysaccharides thus modified their biological activities. PMID- 20363125 TI - Phytoremediation potential of Arundo donax in arsenic-contaminated synthetic wastewater. AB - The present study reports the potential of Arundo donax for phytoextraction of arsenic from synthetic wastewater. A. donax plants were grown under greenhouse conditions in pots containing a nutrient solution amended with increasing doses of As (0, 50, 100, 300, 600 and 1000 microg L(-1)) for 21 days in a completely randomized design. Shoot and roots dry matter production, growth parameters, arsenic and nutrient tissue concentrations were measured at the end of the experiment. Increasing As concentration in nutrient solution caused an increase in shoot and root biomass without toxicity symptoms in A. donax growing under a range of As concentration from 50 to 600 microg L(-1). Elevated oxidative stress was observed at As supplied level of 1000 microg L(-1). The As doses up to 600 microg L(-1) did not affect the growth of A. donax. It is suggested that A. donax plants may be employed to treat contaminated waters containing arsenic concentrations up to 600 microg L(-1). PMID- 20363126 TI - The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors. AB - The design and development of a series of highly selective pyrrolidine carboxamide 11beta-HSD1 inhibitors are described. These compounds including PF 877423 demonstrated potent in vitro activity against both human and mouse 11beta HSD1 enzymes. In an in vivo assay, PF-877423 inhibited the conversion of cortisone to cortisol. Structure guided optimization effort yielded potent and stable 11beta-HSD1 selective inhibitor 42. PMID- 20363127 TI - Expression and characterization of Mycobacterium tuberculosis methionine aminopeptidase type 1a. AB - Methionine aminopeptidase (MetAP) carries out the cotranslational N-terminal methionine excision and is essential for bacterial survival. Mycobacterium tuberculosis expresses two MetAPs, MtMetAP1a and MtMetAP1c, at different levels in growing and stationary phases, and both are potential targets to develop novel antitubercular therapeutics. Recombinant MtMetAP1a was purified as an apoenzyme, and metal binding and activation were characterized with an activity assay using a fluorogenic substrate. Ni(II), Co(II) and Fe(II) bound tightly at micromolar concentrations, and Ni(II) was the most efficient activator for the MetAP catalyzed substrate hydrolysis. Although the characteristics of metal binding and activation are similar to MtMetAP1c we characterized before, MtMetAP1a was significantly more active, and more importantly, a set of inhibitors displayed completely different inhibitory profiles on the two mycobacterial MetAPs in both potency and metalloform selectivity. The differences in catalysis and inhibition predicted the significant differences in active site structure. PMID- 20363128 TI - Optimization of 7-alkene-3-quinolinecarbonitriles as Src kinase inhibitors. AB - The 7-alkene-3-quinolinecarbonitrile 20, a potent inhibitor of Src enzymatic and cellular activity with IC(50) values of 2.1 and 58 nM, respectively, had comparable efficacy to bosutinib in a colon tumor xenograft study. PMID- 20363129 TI - Inhibition of antigen-induced degranulation by aryl compounds isolated from the bark of Betula platyphylla in RBL-2H3 cells. AB - The methanolic extract of the bark of Betula platyphylla was found to suppress antigen mediated degranulation of RBL-2H3 cells. Four arylbutanoids (1-4) and eight diarylhepatonoids (5-12) were isolated from the methanolic extract using bioassay-guided fractionation. Among them, compounds 4 and 12 were isolated and assigned for the first time. Compounds 1, 2, 3, 5, 10, and 12 showed remarkable inhibitory activity against the degranulation of RBL-2H3 by antigen stimulation in a dose dependent manner at the concentrations ranging from 10 microM to 100 microM. PMID- 20363130 TI - Selective targeting of 2'-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro. AB - A urokinase targeting conjugate of 2'-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2'-deoxy-5-fluoro-3'-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile succinate linker was attached to the specific urokinase inhibitor plasminogen activator inhibitor type II (PAI-2) and was found to preferentially kill urokinase-over expressing cancer cells. Up to 7 molecules of 5-FUdr were incorporated per PAI-2 molecule without affecting protein activity. This is the first time a small organic cytotoxin has been conjugated to PAI-2. PMID- 20363131 TI - Design of new dopamine D2 receptor ligands: biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581. AB - LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC-MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors. PMID- 20363132 TI - Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2 diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern. AB - The cannabinoid CB(1)/CB(2) receptor subtype selectivity in the 1,2 diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5 substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than approximately 840-fold CB(1)/CB(2) subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB(1) mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21. PMID- 20363133 TI - Exploration of secondary and tertiary pharmacophores in unsymmetrical N,N'-diaryl urea inhibitors of soluble epoxide hydrolase. AB - The impact of various secondary and tertiary pharmacophores on in vitro potency of soluble epoxide hydrolase (sEH) inhibitors based on the unsymmetrical urea scaffold 1 is discussed. N,N'-Diaryl urea inhibitors of soluble epoxide hydrolase exhibit subtle variations in inhibitory potency depending on the secondary pharmacophore but tolerate considerable structural variation in the second linker/tertiary pharmacophore fragment. PMID- 20363134 TI - Rasch-built myotonic dystrophy type 1 activity and participation scale (DM1 Activ). AB - We describe the development of an outcome measure of activity and participation for patients with myotonic dystrophy type 1 using the Rasch measurement model. A 49-item questionnaire was completed by 163 DM1 patients. Data were subsequently analyzed with Rasch software to design the item set to fit model expectations. Through systematic investigation of response category ordering, model fit, item bias, and local response dependency, we succeeded in constructing a 20-item unidimensional scale of activity and participation (DM1-Activ). High internal consistency (PSI=0.95) and good test-retest reliability values of item difficulty hierarchy and patient location were demonstrated. Patient measures had acceptable correlations with MRC sum scores and MIRS grades (ICC=0.69 and 0.71, respectively), indicating good external construct validity. DM1-Activ is a practical, reliable and valid outcome measure that fulfils all clinimetric requirements. Further evaluation of this scale is needed to provide a nomogram for clinical use. PMID- 20363135 TI - Osteonecrosis of the jaw (ONJ) risk in breast cancer patients after zoledronic acid treatment. PMID- 20363136 TI - Number of strides required for reliable measurements of pace, rhythm and variability parameters of gait during normal and dual task walking in older individuals. AB - The reliability with which spatiotemporal gait parameters are measured has neither been well-established for variability parameters nor during dual task walking. The purpose of this study was to examine test-retest reliability of three gait parameters representing pace, rhythm and variability in healthy older persons during normal and dual task walking and to determine the number of strides necessary to measure the parameters reliably. Twenty-four healthy adults aged 65 or older participated in the study. Subjects walked during normal and dual task (backward spelling) walking conditions at self-selected speeds and then repeated the tests. Velocity, cadence and variability in stride velocity were measured with GAITRite instrumentation. Intraclass correlation coefficients (ICCs) were calculated and the numbers of strides required to meet desired magnitudes of reliability were estimated with the Spearman-Brown prophecy formula. ICCs for velocity and cadence were high (>0.841) during normal and dual task walking, indicating strong test-retest reliability. Test-retest reliability for variability in stride velocity was moderate (ICC=0.656) in normal walking and poor (ICC=0.226) in dual task walking. While data collected from fewer than 10 to 20 strides may reliably measure velocity and cadence in either normal or dual task walking, measuring variability in stride velocity reliably may require that data be collected from hundreds of strides, particularly in dual task walking. PMID- 20363137 TI - Walking abilities of young adults with cerebral palsy: changes after multilevel surgery and adolescence. AB - Although there is some evidence to support the efficacy of single event multilevel surgery (SEMLS) in the short term for improving walking abilities in children with cerebral palsy (CP), long term effects are not known. It is hypothesized: (1) SEMLS improves walking abilities; (2) in young adulthood abilities deteriorate beyond pre-operative status; (3) walking abilities deteriorate from adolescence to young adulthood and are associated with weight status increase. Twenty-three young adults (mean age 25.5 years, range 20-36) with spastic CP Gross Motor Functional Classification Scale Level II (n=11) or III (n=12) returned for follow up three dimensional gait analysis (3DGA). Gillette Gait Index (GGI) was used as a general indicator of walking abilities. Eleven subjects had 3DGA prior to multilevel orthopedic surgery and 12 subjects had 3DGA after the age of 10 with no interventions in the interim. GGI(s) were graphed over time. Ten of 11 subjects (91%) who had multilevel surgery either improved (n=6) or maintained pre-operative walking abilities (n=4) based on GGI. Ten of 12 subjects (83%) who had 3DGA after the age of 10 but no interventions in the interim maintained (n=8) or improved (n=2) walking abilities. No associations were found between declines in walking abilities and increased weight status. After SEMLS, walking abilities in young adulthood were comparable to pre operative status. A decline in walking abilities was not observed from adolescence to young adulthood. PMID- 20363138 TI - The effects of everyday concurrent tasks on overground minimum toe clearance and gait parameters. AB - Deaths and injuries resulting from falls are a significant problem for older adults. Over half of falls during walking result from a trip, and these are likely to begin when the foot contacts the ground at the point of minimum toe clearance (MTC) during the swing phase where the foot most closely approaches the ground. MTC is commonly investigated using a limited number of points and on a treadmill, which cannot account for flooring irregularities, speed changes, and direction changes of overground gait. This paper presents a new method of calculating 3D overground MTC that accounts for flooring variations and utilizes hundreds of points on each shoe. These methods are applied to 10 unimpaired adults during habitual gait: (1) without a concurrent task, (2) while carrying a 9-kg laundry basket, (3) while carrying a tray with a full glass of water on it, and (4) while answering standardized conversational questions. Results indicated that steps were slower and shorter during concurrent tasks while MTC changes were dependent on task type (higher for basket, lower for questions, and unchanged for water). Task-related MTC changes were independent of spatiotemporal gait changes. Thus, MTC during overground gait, particularly while concurrent tasks are being performed, may be an independent fall risk factor that merits further investigation in subjects at-risk of falls. The relationships between MTC, gait parameters, and older age or fall risk should be explored further in at-risk subjects and circumstances to elucidate potential tripping mechanisms. PMID- 20363139 TI - Changes in preferred postural patterns following stroke during intentional ankle/hip coordination. AB - We compared the spatio-temporal postural organization between stroke patients and healthy controls in a bipedal standing task where participants had to intentionally produce two specific ankle/hip coordination patterns: in-phase and anti-phase. The pattern to reproduce was visually represented by a ankle-hip Lissajous figure, and a real-time biofeedback displayed the current coordination sur-imposed to the expected coordination. Contrary to the healthy participants who were successful at reproducing the two patterns, stroke patients were unable to produce the in-phase pattern. In addition, when the anti-phase pattern was required, a reduction of stability was observed for the stroke group. The impairment of postural capacities following stroke was thus accompanied by a disappearance of one of the two preferred patterns found in healthy participants, a result that have consequences for understanding the etiology of postural pattern formation and the elaboration of rehabilitation programs. PMID- 20363140 TI - Allosteric inhibitors of hepatitis C virus NS5B polymerase thumb domain site II: structure-based design and synthesis of new templates. AB - Chronic hepatitis C virus (HCV) infections are a significant medical problem worldwide. The NS5B Polymerase of HCV plays a central role in virus replication and is a prime target for the discovery of new treatment options. We recently disclosed 1H-benzo[de]isoquinoline-1,3(2H)-diones as allosteric inhibitors of NS5B Polymerase. Structural and SAR information guided us in the modification of the core structure leading to new templates with improved activity and toxicity/activity window. PMID- 20363141 TI - Synthesis, anticonvulsant and antimicrobial activities of some new 2 acetylnaphthalene derivatives. AB - In this study, as a continuation of our research for new (arylalkyl)imidazole anticonvulsant compounds, the design, synthesis and anticonvulsant/antimicrobial activity evaluation of a series of 2-acetylnaphthalene derivatives have been described. Molecular design of the compounds has been based on the modification of nafimidone [1-(2-naphthyl)-2-(imidazol-1-yl)ethanone], which is a representative of the (arylalkyl)imidazole anticonvulsant compounds as well as its active metabolite, nafimidone alcohol (3, 4). In general, these compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings and subjected to some other modifications to evaluate additional structure activity relationships. The anticonvulsant activity profile of those compounds was determined by maximal electroshock seizure (MES) and subcutaneous metrazol (scM) seizure tests, whereas their neurotoxicity was examined using rotarod test. All the ester derivatives of nafimidone alcohol (5a-h), which were designed as prodrugs, showed anticonvulsant activity against MES-induced seizure model. Four of the most active compounds were chosen for further anticonvulsant evaluations. Quantification of anticonvulsant protection was calculated via the ip route (ED(50) and TD(50)) for the most active candidate (5d). Observed protection in the MES model was 38.46mgkg(-1) and 123.83mgkg(-1) in mice and 20.44mgkg(-1), 56.36mgkg(-1) in rats, respectively. Most of the compounds with imidazole ring also showed antibacterial and/or antifungal activities to a certain extent in addition to their anticonvulsant activity. PMID- 20363142 TI - Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells. AB - Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate (3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp mediated MDR against KB-C2 cells. 3-O-(Morpholino-beta-oxopropanoyl)-12beta acetoxy-3alpha,25-dihydroxy-(20S,24R)-epoxydammarane (37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5microg/mL (7.4microM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil. PMID- 20363143 TI - Nanoscale enzyme inhibitors: fullerenes inhibit carbonic anhydrase by occluding the active site entrance. AB - We investigated a series of derivatized fullerenes possessing alcohol, amine, and amino acid pendant groups as inhibitors of the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). We discovered that fullerenes bind CAs with submicromolar-low micromolar affinity, despite the fact that these compounds do not possess moieties normally associated with CA inhibitors such as the sulfonamides and their isosteres, or the coumarins. The 13 different mammalian CA isoforms showed a diverse inhibition profile with these compounds. By means of computational methods we assessed the inhibition mechanism as being due to occlusion of the active site entrance by means of the fullerene cage (possessing dimension of the same order of magnitude as the opening of the enzyme cavity, of 1nm). The pendant moieties to the fullerene cage make interactions with amino acid residues from the active site, among which His64, His94, His96, Val121, and Thr200. Fullerenes thus represent a totally new class of nanoscale CA inhibitors which may show applications for targeting physiologically relevant isoforms, such as the dominant CA II and the tumor-associated CA IX. PMID- 20363144 TI - Synthesis of a biologically active isomer of kotalanol, a naturally occurring glucosidase inhibitor. AB - The syntheses of an isomer of kotalanol, a naturally occurring glucosidase inhibitor, and of kotalanol itself are described. The target compounds were synthesized by nucleophilic attack of PMB-protected 1,4-anhydro-4-thio-d arabinitol at the least hindered carbon atom of two 1,3-cyclic sulfates, which were synthesized from d-mannose. Methoxymethyl ether and isopropylidene were chosen as protecting groups. The latter group was critical to ensure the facile deprotection of the coupled products in a one-step sequence to yield kotalanol and its isomer. The stereoisomer of kotalanol, with the opposite stereochemistry at the C-6' stereogenic centre, inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a K(i) value of 0.20+/ 0.02microM; this compares to a K(i) value for kotalanol of 0.19+/-0.03microM. The results indicate that the configuration at C-6' is inconsequential for inhibitory activity against this enzyme. PMID- 20363145 TI - Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages. AB - A novel series of diphenolic chromone derivatives were synthesized and their inhibitory activity on nitric oxide (NO) production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, (5,7-dihydroxy-4-oxo-4H-chromen-3-yl) methyl esters (6b, 6c, 6f, 6g, and 6h) showed quite potent inhibitory activities with IC(50) values of 2.20, 3.48, 0.35, 0.80, and 0.61microM, respectively. The MTT results showed that all of the active compounds exhibited no cytotoxicity at the effective concentrations. The preliminary mechanism of the most potent compounds (6b, 6c, 6f, 6g, and 6h) was further examined based on the RT-PCR results and the compounds 6f, 6g, and 6h inhibited NO production by suppressing the expression of iNOS mRNA in a dose dependent manner. Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug like properties. PMID- 20363146 TI - Preparation and preclinical pharmacological study on a novel bone imaging agent (99m)Tc-EMIDP. AB - A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2-ethyl-4-methyl-1H imidazol-1-yl)ethane-1,1-diyldiphosphonic acid (EMIDP), was prepared and labeled with (99)(m)Tc successfully in a high labeling yield and good stability in vitro. The preclinical pharmacological properties of (99)(m)Tc-EMIDP were investigated and compared with (99)(m)Tc-MDP and (99)(m)Tc-ZL. The studies of biodistribution in mice and SPECT bone imaging of the rabbit suggest that (99)(m)Tc-EMIDP has highly selective uptake in the skeletal system and rapid clearance in the soft tissues. The present findings indicate that (99)(m)Tc-EMIDP holds great potential for bone scintigraphy. PMID- 20363147 TI - Repair of chronic ischemic mitral regurgitation with posterior leaflet extension. PMID- 20363148 TI - Prognostic factors in flail-chest patients. AB - OBJECTIVE: The records of 250 patients presenting with flail-chest injury in a level I trauma centre were reviewed and analysed in order to determine prognostic factors. METHODS: There were 250 consecutive trauma patients with flail chest, 183 men (73.2%) and 67 women (26.8%) ranging in age from 18 to 91 years, admitted to our hospital. The leading cause of injury was road traffic accident. One hundred and six patients (42.4%) were conservatively treated, while 117 (46.8%) needed thoracic drainage. Ventilatory assistance was used in 28 cases (11.2%). Only 19 (7.6%) required thoracotomy and/or laparotomy. The mortality rate reached 8.8%. Patients were divided into three groups: group I consisted of 105 patients (70/35) with an isolated flail chest (Injury Severity Score (ISS): 16); group II included 58 cases (48/10) with extrathoracic fractures (ISS: 25-30); and group III comprised 87 patients (65/22) with injuries to the brain or to thoracic or abdominal organs requiring thoracotomy and/or laparotomy (ISS: >40). Parameters such as age, sex, ISS, presence of extrathoracic fractures, haemopneumothorax and head injury as well as the need for mechanical support in an intensive care unit (ICU) and mortality were evaluated. RESULTS: The mortality rate in group III was higher compared to those of groups I and II (16% vs 3.8% and 6.9%, respectively) and the difference was found to be statistically significant. Laparotomy and thoracotomy affected mortality, while age, pneumothorax and head injury did not. Finally, mechanical support was used only in a few cases. CONCLUSIONS: (1) ISS is the strongest predictor of outcome associated with increased mortality; and (2) mechanical support was not considered a necessity for the treatment of flail chest. PMID- 20363149 TI - Thoracodorsal versus reversed mobilisation of the latissimus dorsi muscle for intrathoracic transposition. AB - OBJECTIVE: The objective of our study is to perform a comparative analysis of the mobilisation of latissimus dorsi (LD) muscle flap using the primary versus secondary blood supply. METHOD: Between 1 January 2003 and 1 March 2009 we used the LD muscle flap in 57 patients with different intrathoracic suppurations; these patients were divided according to the blood supply used for flap mobilisation. Group A consists of 26 patients in whom the LD was mobilised based on the thoracodorsal vessels (alone in eight patients, in combination with other flaps in 18 patients). Group B consists of 31 patients in whom the LD was mobilised based on the perforator branches from the last intercostals and lumbar vessels (alone in nine patients, in combination with other flaps in 22 patients). Statistical analysis was performed using the GraphPad Prism 5 and EpiInfo 3.5.1 for Windows software. RESULTS: The two groups were similar in age, sex distribution, incidence of tuberculosis, bronchial fistula, postoperative empyema and co-morbidities (p>0.05). We found no statistically significant difference between group A and group B in terms of operative time group (176 +/- 33 min vs group B 170 +/- 40 min), mortality (4% vs 3%), infection recurrence (8% vs 3%), incidence of minor local complications (8% vs 6%) or hospitalisation 39 +/- 16 days versus 41 +/- 16 days (p>0.05 for all the parameters). We encountered no significant functional sequelae in any of the 57 patients. CONCLUSIONS: Both modalities of mobilisation of the LD muscle flap are safe and allow easy transposition in any part of the chest; the choice of how to use this flap should be made based only on the location of the intrathoracic defect. PMID- 20363150 TI - The impact of preoperative atrial fibrillation on early and late mortality after coronary artery bypass grafting. AB - OBJECTIVES: There are still doubts on the effect of preoperative atrial fibrillation (AF) on early and late mortality after coronary artery bypass grafting (CABG). This retrospective study demonstrates the effects of preoperative AF on the short-term and long-term survival after CABG. METHODS: We retrospectively analysed the data of 10626 patients who underwent CABG between January 1998 and December 2007. The data of 221 patients with a history of preoperative AF (2.5%) and 8631 patients with preoperative sinus rhythm were eligible for analysis. Survival of these patient groups was compared to survival of age- and sex-matched groups of the Dutch general population. RESULTS: Mean follow-up duration was 4.6 + or - 2.9 years. Multivariate logistic regression analysis showed preoperative AF to be an independent risk factor for early mortality after CABG, with an odds ratio of 2.06 (95% confidence interval (CI): 1.08-3.95; P=0.029). Multivariate Cox proportional hazard analysis revealed that preoperative AF is an independent risk factor for late mortality after CABG, with a hazard ratio (HR) of 1.67 (95% CI: 1.21-2.31; P=0.002). Using propensity score matching, AF was also an independent risk factor for late mortality after CABG, with an HR of 2.77 (95% CI: 1.6-4.79; P<0.001). In comparison with the general Dutch population, patients with preoperative AF who undergo CABG have a worse long-term survival, while patients with preoperative sinus rhythm experience a better survival. CONCLUSIONS: Preoperative AF is an independent risk factor for early and late mortality after first-time elective CABG. PMID- 20363151 TI - Interleukin 10 polymorphisms differentially influence the risk of gastric cancer in East Asians and Caucasians. AB - BACKGROUND: Although a number of association studies of gastric cancer (GC) risk have been conducted worldwide, their results have been inconsistent among different populations. The association between GC incidence and Helicobacter pylori (H. pylori) infection is somewhat of an enigma that has yet to be clearly explained. Geographically-restricted positive selection due to unique environmental pressures often result in large allele frequency differences between populations. Thus, population differences need to be investigated when attempting to identify genes that contribute to phenotypes that differ greatly between populations. METHODS: We analyzed population differences in 18 polymorphisms of 12 GC-associated or immune response-related genes from 3 ethnic groups comprising 50 Koreans, 46 Indians, and 60 Caucasians; these groups differed in H. pylori seropositivity and susceptibility to GC. RESULTS: An interleukin 10 (IL10) polymorphism demonstrated a significantly different genotype distribution (F(ST)=0.306, P=0.014), indicating a large difference between the Korean and Caucasian populations. The odds ratio of IL10 polymorphism allele between the populations was 38.32 (95% confidence interval, 11.49-127.83). CONCLUSION: This finding, taken together with previous evidence, provides a possible explanation for previous discrepant association results and supports the idea that IL10 gene polymorphisms can differentially affect GC development among populations. PMID- 20363152 TI - Vibration stimulation during non-fatiguing tonic contraction induces outlasting neuroplastic effects. AB - The objective was to explore if vibration superposed to tonic contraction induces plastic changes in the contra- and ipsilateral motor cortex. Healthy subjects (n=12) abducted the right index finger with a force 5% of maximal voluntary contraction (MVC) against the lever of a torque motor while a 60 Hz vibration stimulus of 10 min was delivered. Motor evoked potentials (MEPs) after single and paired-pulse transcranial magnetic stimulation (TMS) were recorded from the first dorsal interosseous muscle of right and left hand pre, during, post and 30 min post-stimulation. The TMS assessments were employed with tonic contraction alone (TONIC) and with superposed vibrostimulation (VIBRO), each for the ipsi- and contralateral cortex separately. In the contralateral cortex: resting motor threshold (rMT) decreased, MEP amplitudes increased, short-interval intracortical inhibition (SICI) reduced and intracortical facilitation (ICF) increased post VIBRO, while no changes occurred post TONIC. In the ipsilateral cortex: rMT decreased, MEP amplitude increased and SICI reduced during TONIC, while no changes occurred post TONIC, during and post VIBRO. Vibration superposed to tonic contraction, induces lasting (30 min) plastic changes, whereas contraction alone caused no outlasting effects. Mainly intrinsic intracortical mechanisms are involved because spinal adaptation could be excluded (F-wave assessments). These findings have a therapeutic potential in the functional recovery of motor deficits with robot-aided devices. PMID- 20363153 TI - Contrast-enhanced ultrasound versus computed tomographic angiography for surveillance of endovascular abdominal aortic aneurysm repair. AB - PURPOSE: To compare diagnostic accuracy between contrast-enhanced ultrasound (US) and computed tomographic (CT) angiography to detect changes in abdominal aortic aneurysm (AAA) size and endoleaks during follow-up after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Between May 2006 and December 2008, 83 patients were consecutively enrolled for contrast-enhanced US and CT angiography imaging during surveillance after EVAR, yielding 127 paired examinations. Comparative analysis was performed for the anteroposterior and transverse maximal diameters of the aneurysm sac and for the presence or absence of endoleak, as determined by US and CT angiography. RESULTS: Contrast-enhanced US demonstrated significantly more endoleaks, predominantly of type II, compared with CT angiography (53% vs 22% of cases). The number of observed agreements was 77 of 127 (61%), indicating a low level of agreement (kappa value of 0.237). US was as accurate as CT angiography in the assessment of maximal aneurysm sac diameters, as shown by Bland-Altman analyses and low coefficients of variation (8.0% and 8.6%, respectively). The interobserver variability for AAA size measurement by US was low, given the interclass correlation coefficients of 0.99 and 0.98 for anteroposterior and transverse maximal diameters, respectively. CONCLUSIONS: Contrast-enhanced US may be an alternative to CT angiography in the follow-up of patients after EVAR. As US reduces exposure to the biologic hazards associated with lifelong annual CT angiography, including cumulative radiation dose and nephrotoxic contrast agent load, contrast-enhanced US might be considered as a substitute for CT angiography in the surveillance of patients after EVAR. PMID- 20363154 TI - Minimally invasive, off-pump explant of a continuous-flow left ventricular assist device. AB - The left ventricular assist device (LVAD) has been used successfully for bridge to transplant and destination therapy. In some cases, myocardial recovery is possible and allows LVAD explantation. We describe a novel explant technique for the HeartMate II LVAD using small incisions on a beating heart, without cardiopulmonary bypass. PMID- 20363155 TI - In praise of ventricular assist devices-mechanical bridge to virtual crossmatch for the sensitized patient. AB - Human leukocyte antigen (HLA) sensitization is a common problem in patients being assessed for organ transplantation. Two overarching principles that must be adhered to when evaluating approaches to sensitized patients are: (1) ensuring equitable access for potential recipients to transplantable organs; and (2) maintaining optimal long-term patient and graft outcomes post-transplant. Approaches increasingly used to manage sensitized heart transplant candidates are crossmatching (virtual [VXM], based on comparison of donor HLA to recipient antibody specificities, or prospective real-time [XM]) to avoid donor-specific antibodies, or desensitization to reduce the amount of antibodies that are present. We propose that the best strategy for management of highly sensitized patients awaiting heart transplantation is combining mechanical circulatory support as a bridge to a (-) VXM or XM together with adoption of a national prioritized sharing algorithm for highly sensitized patients. PMID- 20363156 TI - Therapy with sildenafil or bosentan decreases pulmonary vascular resistance in patients ineligible for heart transplantation because of severe pulmonary hypertension. PMID- 20363157 TI - Visuospatial perspective taking in a dynamic environment: perceiving moving objects from a first-person-perspective induces a disposition to act. AB - Spatial perspective taking is an everyday cognitive process that is involved in predicting the outcome of goal directed behavior. We used dynamic virtual stimuli and fMRI to investigate at the neural level whether motion perception interacts with spatial perspective taking in a life-like design. Subjects were asked to perform right-left-decisions about the position of either a motionless, hovering (STATic) or a flying ball (DYNamic), either from their own (1PP) or from the perspective of a virtual character (avatar, 3PP). Our results showed a significant interaction of STIMULUS TYPE and PERSPECTIVE with significantly increased activation in right posterior intraparietal sulcus (IPS) for 1PPDYN condition. As the IPS is critically involved in the computation of object directed action preparation, we suppose that the simple perception of potentially action-relevant dynamic objects induces a 'readiness for (re)action', restricted to the 1PP. Results are discussed against the background of current theories on embodiment and enactive perception. PMID- 20363158 TI - A prospective randomized study comparing a forearm strap brace versus a wrist splint for the treatment of lateral epicondylitis. AB - BACKGROUND: The outcome is unknown for 2 common bracing treatments utilized for patients with lateral epicondylitis. The purpose of this study was to compare the clinical outcomes of a wrist splint with that of a counterforce forearm strap for the management of acute lateral epicondylitis. MATERIALS AND METHODS: Forty-two patients (44 elbows) received either a wrist extension splint (Group I-24 elbows) or a counterforce forearm strap (Group II-20 elbows). Measures on the Mayo Elbow Performance (MEP) and American Shoulder and Elbow Society (ASES) Elbow Assessment Form were collected prior to treatment and at 6 weeks. A total score was derived, utilizing the ASES Elbow Assessment, as was a score utilizing the standard scoring system for the MEP. RESULTS: Group I's score derived from the ASES form improved 16 points and Group II's score improved 13 points. Group I's score on the MEP improved 13 points and Group II's score improved 12 points. There was no significant difference measured between the Groups with the ASES (P = .60) nor MEP (P = .63) scores. However, within the ASES derived score, pain relief was significantly better with the extension splint group (P = .027). No other variables were statistically significantly different. DISCUSSION: Significant pain relief with the wrist extension splint may be due to improved immobilization of the wrist extensor muscles in a resting position. CONCLUSION: The wrist extension splint allows a greater degree of pain relief than does the forearm strap brace for patients with lateral epicondylitis. PMID- 20363159 TI - Reverse shoulder arthroplasty in patients with rheumatoid arthritis. AB - BACKGROUND: The purpose of this study was to describe the pathoanatomy of patients diagnosed with rheumatoid arthritis and rotator cuff deficiency and report their outcomes following reverse shoulder arthroplasty. METHODS: Twenty one shoulders were evaluated prospectively. Nine had no prior surgery, 9 had a failed rotator cuff repair, and 3 had a failed arthroplasty. Patients were followed for a minimum of 2 years (average, 36 months). All patients had preoperative radiographs and 19 shoulders had an MRI or CT available for evaluation of muscular and bony deficiency. Radiographs at most recent follow-up were evaluated for loosening and scapular notching. RESULTS: All outcome measures improved significantly: ASES scores improved from 28 preoperatively to 82 postoperatively (P < .0001); SST scores improved from 1 to 7 (P < .0001); VAS pain scores improved from 7 to 1 (P < .0001); VAS function scores improved from 3 to 6 (P=.0058); elevation improved from 52 degrees to 126 degrees (P < .0001); abduction improved from 55 degrees to 116 degrees (P=.0002); external rotation improved from 19 degrees to 33 degrees (P=.02); and internal rotation improved from S1 to L4 (P=.02). Twelve patients rated their outcome as excellent, 6 as good, 2 as satisfactory, and 1 as unsatisfactory. Severe glenoid erosion was seen in 10 of the shoulders and 5 of the defects required structural grafting. Three patients (14%) sustained a complication that required reoperation: 2 for infection and 1 for periprosthetic fracture. CONCLUSIONS: In patients with rheumatoid arthritis and rotator cuff deficiency, reverse shoulder arthroplasty can provide improvement in function and decreased pain. PMID- 20363160 TI - Natural history of infraspinatus fatty infiltration in rotator cuff tears. AB - BACKGROUND/HYPOTHESIS: Muscular fatty infiltration (FI) represents an important prognostic factor in rotator cuff repair. The goal of this study was to analyze the natural history of infraspinatus FI in rotator cuff tears to determine the timing of the appearance and the speed of progression of this phenomenon. METHOD: The preoperative MRI or CT-arthrograms of 1688 patients operated for rotator cuff tears were reviewed. The degree of infraspinatus FI was correlated with the type of tendon tear, patient sex, dominant hand, presence of traumatic injury, delay between the onset of symptoms and imaging studies, and age of the patients at imaging. Infraspinatus FI was graded on axial images according to Goutallier classification and described as minimal (stage 0 or 1), medium (stage 2), and severe (stages 3 and 4). Statistical regression was used to determine the most significant factors. RESULTS: Infraspinatus FI increased significantly in presence of an infraspinatus tendon tear and when multiple tendons were torn (P < .0005), with increasing delay between the onset of symptoms and imaging studies (P < .0005) and increasing patient age (P < .0005). Medium FI appeared on average 2 and a half years after the onset of symptoms, and severe FI appeared at an average of 4 years after symptom onset. CONCLUSION: Larger tendon tears, longer delays after tendon rupture and older patient age are associated with more severe and frequent FI. Stage 2 FI appears at an average of 2 and a half years after the onset of symptoms, and surgical repair should be done within this time frame if possible. PMID- 20363161 TI - Relationship between coronary artery disease and epicardial adipose tissue quantification at cardiac CT: comparison between automatic volumetric measurement and manual bidimensional estimation. AB - RATIONALE AND OBJECTIVES: The aim of this study was to compare the reproducibility of bidimensional and volumetric quantification of epicardial adipose tissue (EAT) on cardiac computed tomography (CT) and evaluate their relationship with the extent of coronary artery disease (CAD). MATERIALS AND METHODS: Forty-five individuals underwent cardiac dual-source CT and conventional coronary angiography for suspicion of CAD. Nonenhanced images acquired to assess calcium score were used to quantify EAT. Coronary stenosis grading was performed on conventional coronary angiograms using Gensini scores. Two independent observers manually measured right ventricular EAT thickness at three different levels and in two different planes (four chamber and short axis) to obtain mean values. Additionally, EAT volume was automatically determined using a commercially available software tool. RESULTS: Conventional coronary angiography demonstrated nonstenotic coronary arteries in 22 subjects and significant coronary artery stenosis in 23. Significant correlations were observed between volumetric estimation of EAT and body mass index, coronary artery calcification, and Gensini score. On automatic volumetry, patients with significant coronary artery stenosis had significantly greater EAT volumes (154.58 +/- 58.91 mL) than those without significant CAD (120.94 +/- 81.85 mL) (P = .016). The manual bidimensional approach based on thickness measurements failed to show a significant difference between the two groups. Reproducibility and interobserver agreement for EAT quantification were higher when the automatic volumetric method was used (concordance-correlation coefficient, 0.96) compared to manual measurements (concordance-correlation coefficients, 0.37 for four-chamber EAT, 0.53 for short-axis EAT, and 0.58 for average EAT). CONCLUSIONS: For the quantification of EAT on cardiac CT, automated volumetry is more reproducible and correlates better with the extent of CAD than manual bidimensional measurements. PMID- 20363162 TI - Surveillance Epidemiology and End Results (SEER) program and population-based research in urologic oncology: an overview. AB - The Surveillance, Epidemiology, and End Results (SEER) program is a commonly used data source in cancer research. This article provides an introduction to the SEER database, describes important data items available from SEER on the most commonly diagnosed urologic malignancies (prostate, bladder, and kidney cancers), and reviews limitations of SEER data for urologic oncology research. PMID- 20363163 TI - Significant activity of single agent vinorelbine against small-cell cancer of the bladder as second line chemotherapy: a case series and review of the literature. AB - Small-cell carcinoma of the urinary bladder is an extremely uncommon form of urologic malignancy, accounting for less that 1% of new cases of bladder cancer. It is an aggressive malignancy which, like its pulmonary counterpart, tends to spread with distant metastases. This malignancy is generally chemotherapy and radiotherapy sensitive. Metastatic disease is typically treated with regimens active against small-cell carcinoma of the lung, such as cisplatin and etoposide. There are no data regarding second-line treatment of this cancer. We report our experience in 3 patients using the second generation vinca alkaloid, vinorelbine, in refractory metastatic small-cell carcinoma of the bladder. These 3 patients had extensive prior therapy but all 3 responded to weekly vinorelbine, with a complete response (CR) in 1, near CR in the second, and partial response in the third. Of note, the patient who sustained a CR has remained without disease and with excellent quality of life for nearly 4 years since starting vinorelbine. Indeed, the therapy was very well tolerated in all 3 patients with grade 2 cytopenia being the only toxicity. We conclude that vinorelbine is well tolerated and has activity in this case series in the second-line treatment of metastatic small-cell carcinoma of the bladder. PMID- 20363164 TI - Outcome prediction for prostate cancer detection rate with artificial neural network (ANN) in daily routine. AB - BACKGROUND: We evaluated the use of the artificial neural network (ANN) program "ProstataClass" of the Department of Urology and the Institute of Medical Informatics at the Charite-Universitatsmedizin Berlin in daily routine to increase prostate cancer (CaP) detection rate and to reduce unnecessary biopsies. MATERIALS AND METHODS: From May 2005 to April 2007, a total of 204 patients were included in the study. The Beckman Access PSA assay was used, and pretreatment prostate specific antigen (PSA) was measured prior to digital rectal examination (DRE) and 12 core systematic transrectal ultrasound (TRUS) guided biopsies. The individual ANN predictions were generated with the use of the ANN application for the Beckman Access PSA and free PSA assays, which relies on age, PSA, percent free prostate specific antigen (%fPSA), prostate volume, and DRE. Diagnostic validity of total prostate specific antigen (tPSA), %fPSA, and the ANN was evaluated by ROC curve analysis. RESULTS: PSA and %fPSA ranged from 4.01 to 9.91 ng/ml (median: 6.65) and 5% to 48% (median: 15%), respectively. Of all men, 46 (22.5%) demonstrated suspicious DRE findings. Total prostate volume ranged from 7.1 to 119.2 cc (median: 35). Overall, 71 (34.8%) CaP were detected. Of men with suspicious DRE, 28 (60.9%) had CaP on initial biopsy. The ANN was 78% accurate in the original report. The AUC of ROC curve analysis was 0.51 for PSA, 0.66 for %PSA, and 0.72 for the ANN-Output, respectively. CONCLUSIONS: Our results in this independent cohort show that ANN is a very helpful parameter in daily routine to increase the CaP detection rate and reduce unnecessary biopsies. PMID- 20363165 TI - Development of a quantitative real-time PCR assay for detection of unknown alpha globin gene deletions. AB - BACKGROUND: Alpha-Thalassemia is the most common inherited disorder of hemoglobin (Hb) synthesis in the world. Unlike beta-thalassemia, in which non-deletional mutations predominate, most of recognized alpha-thalassemia mutations include deletion of one or both alpha-globin genes. The importance of alpha-thalassemia detection is mainly due to its shared blood parameters with beta-thalassemia and its impact on discrimination between unknown alpha-thalassemia and normal HbA2 beta-thalassemia during thalassemia prevention program. MATERIALS AND METHODS: Cases with hematologic profile of low MCV, MCH, and normal HbA2 were enrolled in this study. Common alpha-globin deletional mutations including alpha(3.7)kb, alpha(4.2)kb, alpha(20.5)kb, and alpha(MED) and point mutation including 5 nt, Constant Spring (CS), and C19 were checked using either GAP-PCR or ARMS-PCR. Cases with unknown molecular defects were investigated further by direct gene sequencing. Finally, further study was done for probable unknown deletions by gene dosage analysis using real-time PCR. For this, five pairs of primers were used spanning from theta-globin gene up to the 3' upstream of alpha(2) gene. RESULTS: After validation of primers specificity and performing serial dilution analysis in order to calculate PCR efficiency, the assay was performed on normal samples and cases with known alpha-globin gene deletions as positive and negative controls, respectively. The assay was able to diagnose the control groups successfully. In 21 out of 29 unknown cases (72.4%), the assay showed various patterns of deletions in at 2 to 5 screened regions (theta gene up to the upstream of alpha2 gene). In 8 (27.6%) cases, deletions were seen in all regions. CONCLUSION: Gene dosage study by quantitative real-time PCR can be suggested as a rapid and reliable assay to screen probable carrier of alpha-thalassemia for unknown alpha-globin gene deletions. PMID- 20363166 TI - The emotional brain and sleep: an intimate relationship. AB - Research findings confirm our own experiences in life where daytime events and especially emotionally stressful events have an impact on sleep quality and well being. Obviously, daytime emotional stress may have a differentiated effect on sleep by influencing sleep physiology and dream patterns, dream content and the emotion within a dream, although its exact role is still unclear. Other effects that have been found are the exaggerated startle response, decreased dream recall and elevated awakening thresholds from rapid eye movement (REM)-sleep, increased or decreased latency to REM-sleep, increased REM-density, REM-sleep duration and the occurrence of arousals in sleep as a marker of sleep disruption. However, not only do daytime events affect sleep, also the quality and amount of sleep influences the way we react to these events and may be an important determinant in general well-being. Sleep seems restorative in daily functioning, whereas deprivation of sleep makes us more sensitive to emotional and stressful stimuli and events in particular. The way sleep impacts next day mood/emotion is thought to be affected particularly via REM-sleep, where we observe a hyperlimbic and hypoactive dorsolateral prefrontal functioning in combination with a normal functioning of the medial prefrontal cortex, probably adaptive in coping with the continuous stream of emotional events we experience. PMID- 20363167 TI - Two novel exonic point mutations in HEXA identified in a juvenile Tay-Sachs patient: role of alternative splicing and nonsense-mediated mRNA decay. AB - We have identified three mutations in the beta-hexoseaminidase A (HEXA) gene in a juvenile Tay-Sachs disease (TSD) patient, which exhibited a reduced level of HEXA mRNA. Two mutations are novel, c.814G>A (p.Gly272Arg) and c.1305C>T (p.=), located in exon 8 and in exon 11, respectively. The third mutation, c.1195A>G (p.Asn399Asp) in exon 11, has been previously characterized as a common polymorphism in African-Americans. Hex A activity measured in TSD Glial cells, transfected with HEXA cDNA constructs bearing these mutations, was unaltered from the activity level measured in normal HEXA cDNA. Analysis of RT-PCR products revealed three aberrant transcripts in the patient, one where exon 8 was absent, one where exon 11 was absent and a third lacking both exons 10 and 11. All three novel transcripts contain frameshifts resulting in premature termination codons (PTCs). Transfection of mini-gene constructs carrying the c.814G>A and c.1305C>T mutations proved that the two mutations result in exon skipping. mRNAs that harbor a PTC are detected and degraded by the nonsense-mediated mRNA decay (NMD) pathway to prevent synthesis of abnormal proteins. However, although NMD is functional in the patient's fibroblasts, aberrant transcripts are still present. We suggest that the level of correctly spliced transcripts as well as the efficiency in which NMD degrade the PTC-containing transcripts, apparently plays an important role in the phenotype severity of the unique patient and thus should be considered as a potential target for drug therapy. PMID- 20363168 TI - Phenylketonuria management from an European perspective: a commentary. AB - Phenylketonuria is discussed from an European perspective, addressing the need of common definitions of terms commonly used, the need of a world-wide guideline on the diagnosis and treatment of phenylketonuria, the differences between existing European guidelines, and day-to-day care, further directives for the near future, and changing the concept from compliance to concordance, in which patients have a more clearly defined responsibility. PMID- 20363169 TI - Characteristics of US public schools with reported cases of novel influenza A (H1N1). AB - OBJECTIVE: The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. METHODS: A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case-control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. RESULTS: Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166-0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670-0.938). CONCLUSIONS: We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread. PMID- 20363170 TI - Abdominal tuberculosis: sonographic diagnosis and treatment response in HIV positive adults in rural South Africa. AB - OBJECTIVE: To investigate the diagnostic value of abdominal ultrasound in HIV positive inpatients in a rural African setting. METHODS: This was a prospective case series over 3 months of adult HIV-positive patients with symptoms suggestive of abdominal tuberculosis (TB). Diagnostic ultrasound was performed for all patients: sonographic criteria included abdominal lymph node enlargement (>1.5cm) and focal splenic lesions; ascites was a supportive finding. Further diagnostic studies, e.g., aspiration or biopsy were not routinely performed. TB treatment was initiated on the basis of clinical and sonographic features. The patients were contacted after 4 months to evaluate the clinical outcome. RESULTS: One hundred and eighty adult HIV-positive patients were screened; 30 (16.7%) showed sonographic signs of abdominal TB. The median CD4 count was 78 cells/mm(3). Presenting symptoms were weight loss (86.7%), abdominal pain (76.7%), and diarrhea (60%). Abdominal lymph node enlargement was the diagnostic finding in almost all cases (96.7%); hypoechoic lesions of the spleen were seen in 50% and ascites in 73.3%. Follow-up information was available for 25 patients: 24% had died and the remaining 76% reported symptomatic improvement and weight gain. CONCLUSIONS: Characteristic sonographic features of abdominal TB are common in HIV-infected inpatients in a rural African setting. Ultrasound should be introduced into clinical algorithms for the diagnosis of extrapulmonary TB. PMID- 20363171 TI - Are elderly patients with diabetes being overtreated in French long-term-care homes? AB - AIM: In France, diabetes prevalence and ageing of the population are both on the increase, yet little information on diabetes in elderly patients living in geriatric institutions is available. Moreover, institutionalized diabetic patients are not included in the French recommendations for the management of diabetes in the elderly. For this reason, the aim of the present study was to evaluate diabetes management in older, institutionalized patients. METHODS: The medical records of 100 diabetic patients, aged 65 years and over, and living in seven geriatric institutions in the Cote d'Or region of France, were studied from May 2008 to January 2009. RESULTS: Prevalence of diabetes in these seven geriatric institutions was 15.46+/-4.9%, higher than in the general population. The diabetic patients had a mean age of 81.85+/-11.93 years, and 32% had glycated haemoglobin (HbA(1c)) less or equal to 6.5%, indicating a high risk of severe hypoglycaemia. A diet for diabetes was prescribed in 54% of the patients, but HbA(1c) levels did not differ between patients following and not following the diet (7.26+/-1.36% vs 7.11+/-1.10%, respectively; P=0.27). Creatinine was assessed in 87% of the patients, and 16% were ophthalmologically followed-up. Daily capillary blood glucose monitoring was performed in 100% of the patients taking insulin and in 17% of those taking oral antidiabetic treatment (P<0.0001). CONCLUSION: Our data show that, among older institutionalized patients, the prevalence of diabetes is high and the control of diabetes too tight, with a potential risk of hypoglycaemia. Antidiabetic treatment should be reduced when the HbA(1c) value is less than 7.5% in this frail and functionally dependent population. Furthermore, a diabetic diet, prescribed for more than half this population, is useless for glycaemic control and may even impinge on quality of life. PMID- 20363173 TI - Location registration and recognition (LRR) for serial analysis of nodules in lung CT scans. AB - In the clinical workflow for lung cancer management, the comparison of nodules between CT scans from subsequent visits by a patient is necessary for timely classification of pulmonary nodules into benign and malignant and for analyzing nodule growth and response to therapy. The algorithm described in this paper takes (a) two temporally-separated CT scans, I(1) and I(2), and (b) a series of nodule locations in I(1), and for each location it produces an affine transformation that maps the locations and their immediate neighborhoods from I(1) to I(2). It does this without deformable registration and without initialization by global affine registration. Requiring the nodule locations to be specified in only one volume provides the clinician more flexibility in investigating the condition of the lung. The algorithm uses a combination of feature extraction, indexing, refinement, and decision processes. Together, these processes essentially "recognize" the neighborhoods. We show on lung CT scans that our technique works at near interactive speed and that the median alignment error of 134 nodules is 1.70mm compared to the error 2.14mm of the Diffeomorphic Demons algorithm, and to the error 3.57mm of the global nodule registration with local refinement. We demonstrate on the alignment of 250 nodules, that the algorithm is robust to changes caused by cancer progression and differences in breathing states, scanning procedures, and patient positioning. Our algorithm may be used both for diagnosis and treatment monitoring of lung cancer. Because of the generic design of the algorithm, it might also be used in other applications that require fast and accurate mapping of regions. PMID- 20363174 TI - Action and the fallacy of the 'internal': Comment on Passingham et al. PMID- 20363175 TI - Weak quantitative standards in linguistics research. PMID- 20363176 TI - Scaling laws in cognitive sciences. AB - Scaling laws are ubiquitous in nature, and they pervade neural, behavioral and linguistic activities. A scaling law suggests the existence of processes or patterns that are repeated across scales of analysis. Although the variables that express a scaling law can vary from one type of activity to the next, the recurrence of scaling laws across so many different systems has prompted a search for unifying principles. In biological systems, scaling laws can reflect adaptive processes of various types and are often linked to complex systems poised near critical points. The same is true for perception, memory, language and other cognitive phenomena. Findings of scaling laws in cognitive science are indicative of scaling invariance in cognitive mechanisms and multiplicative interactions among interdependent components of cognition. PMID- 20363177 TI - Proactive and reactive recruitment of cognitive control: Comment on Hikosaka and Isoda. PMID- 20363178 TI - Towards a bottom-up perspective on animal and human cognition. AB - Over the last few decades, comparative cognitive research has focused on the pinnacles of mental evolution, asking all-or-nothing questions such as which animals (if any) possess a theory of mind, culture, linguistic abilities, future planning, and so on. Research programs adopting this top-down perspective have often pitted one taxon against another, resulting in sharp dividing lines. Insight into the underlying mechanisms has lagged behind. A dramatic change in focus now seems to be under way, however, with increased appreciation that the basic building blocks of cognition might be shared across a wide range of species. We argue that this bottom-up perspective, which focuses on the constituent capacities underlying larger cognitive phenomena, is more in line with both neuroscience and evolutionary biology. PMID- 20363179 TI - Uncommon EEG burst-suppression in severe postanoxic encephalopathy. AB - OBJECTIVE: In patients suffering from severe hypoxia, the EEG may show a burst suppression pattern, characterized by low-voltage activity and the occurrence of high amplitude burst-like events. We describe the two-timescale burst phenomenology of this postanoxic condition. METHODS: We present EEG recordings showing remarkable burst phenomenology in two postanoxic patients and consider potential mechanisms responsible for the generation of the burst-suppression patterns. We quantify the postanoxic condition in terms of the dimension (number of degrees of freedom) of its dynamics by comparing our data with a system of three ordinary differential equations with two timescales subject to varying degrees of noise. RESULTS: EEGs displayed extreme similarity of the bursts, separated by interburst intervals up to more than 300s. This pattern reflects a significant reduction in the number of functional brain states. This post-anoxic condition is found to have dimension 3, consisting of fast dynamics responsible for the bifurcation to bursting behavior, and a long time-scale responsible for burst termination and the interburst intervals. CONCLUSIONS: Low-dimensional postanoxic brain states, as manifested by burst-similarity, appears to indicate an irreversible loss of brain function and consciousness. SIGNIFICANCE: Evidence of brain functionality in a persistent low dimensional state due to severe hypoxia is indicative of permanent loss of consciousness with essentially no chance for recovery. Quantitative evidence for such degenerate states is important for clinical decision making. PMID- 20363180 TI - Auditory evoked potential variability in healthy and schizophrenia subjects. AB - OBJECTIVES: To investigate if the reduced P50, N100 and P200 auditory evoked potential (EP) components and gating deficits seen in schizophrenia can be explained in terms of response incompleteness. METHODS: Twenty-five healthy and schizophrenia participants were studied using pairs of 1000Hz tones (S1 and S2, 0.5s apart) separated by 8.0s. A correlation-based clustering method identified the responses containing P50, N100, and/or P200 related-activity. RESULTS: Schizophrenia participants produced fewer S1 and S2 responses containing all three EP components than healthy participants. Healthy participants, but not the patient population, produced fewer and smaller S2 than S1 responses containing all three EP components. However, the S2 responses following complete S1 responses were smaller than the complete S1 responses in both populations. CONCLUSIONS: The gating deficits observed in schizophrenia are due to two mechanisms. First, the S1 response consistency is less in schizophrenia than in health. Second, the S2 responses are attenuated less in schizophrenia. SIGNIFICANCE: This research contributes to the understanding of response variability and sensory gating in health and schizophrenia. It also extends previous reports that fewer and smaller P300 components are produced in schizophrenia than in health to the mid-latency component range. PMID- 20363181 TI - Developmental changes in somatosensory processing in cerebral palsy and healthy individuals. AB - OBJECTIVE: Cerebral palsy (CP) is a motor disorder that causes physical disability in human development. Recent work has shown that somatosensory deficits are a serious problem for people with CP. There is however no information about the influence of age on brain correlates of tactile sensitivity. METHODS: Proprioception, touch and pain pressure thresholds, as well as somatosensory evoked potentials (SEP) elicited by tactile stimulation in lips and thumbs were examined in 15 children with CP (range 5-14y), 14 adults with CP (range 22-55y), 15 healthy children (range 5-14y), and 15 healthy adults (range 22-42y). RESULTS: Children with CP as compared to healthy controls showed more reduced sensitivity for non-painful stimuli, but enhanced sensitivity for painful stimuli. Early SEP amplitudes (P50 and P100) were more enhanced in children and adults with CP than in healthy participants. A functional hemispheric asymmetry was observed in CP when left- and right-side body parts were stimulated. CONCLUSIONS: Data suggest the possibility that altered somatosensory brain processing in CP might be reflecting an enhanced excitability of the somatosensory cortex. SIGNIFICANCE: Assessment of somatosensory functions may have implications for future neuromodulatory treatment of pain complaints and motor rehabilitation programs in children and adults with cerebral palsy. PMID- 20363182 TI - Increased spike frequency during general anesthesia with etomidate for magnetoencephalography in patients with focal epilepsies. AB - OBJECTIVE: Magnetoencephalography (MEG) is used for focus localization in presurgical evaluation of patients with focal epilepsies. In this proof-of concept study, general anesthesia with etomidate was used to improve effectiveness of MEG-recordings. METHODS: MEG-recordings of six patients with focal epilepsy were performed before and after application of etomidate. Spike frequency and localization accuracy of MEG with general anesthesia were compared with spontaneous MEG. RESULTS: After application of etomidate, an increase in spike frequency occurred in all patients, and movement artifacts were prevented. In one patient, spikes could only be detected by invasive EEG but not by MEG. The results were in accordance with spontaneous MEG or presurgical hypotheses about localizations of neocortical foci in three patients. Dipole localizations were distributed over fronto-temporal areas in three patients with ipsilateral temporo mesial focus hypotheses. CONCLUSIONS: Etomidate ameliorated spike yield and stopped movement artifacts during MEG recordings in patients with focal epilepsy. Localization results were especially accurate in patients with neocortical epilepsy. SIGNIFICANCE: These results could facilitate larger studies on the usefulness and safety of general anesthesia with etomidate that record and localize epileptic activity in patients with focal epilepsy by MEG. PMID- 20363183 TI - Patients with primary biliary cirrhosis do not show post-exercise depression of cortical excitability. AB - OBJECTIVE: Primary biliary cirrhosis (PBC), a female-predominant autoimmune liver disease, is commonly associated with fatigue, a sensation of weariness from physical activity. In healthy subjects, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) increase in amplitude during fatiguing exercise and decrease after the exercise due to post-contraction cortical excitability depression. TMS was utilized herein to investigate if unique cortical excitability changes discriminate women with PBC from healthy controls. METHODS: Twenty-two women (11 with PBC and 11 healthy controls) performed a voluntary submaximal tonic contraction of finger flexor muscles until exhaustion; MEPs were recorded before and during exercise as well as 10min after exercise discontinuation. All subjects completed questionnaires for quality of life and fatigue evaluation. RESULTS: During exercise an increase in MEPs amplitude was observed in all subjects, with no sign of altered peripheral fatigability. Following exercise women with PBC associated with high fatigability showed a significant lack of reduction of MEP size compared to the healthy controls. CONCLUSIONS: Women with PBC do not manifest post-exercise depression of cortical excitability. SIGNIFICANCE: We suggest that an impairment of neural mechanisms underlying physiological central fatigue could occur in PBC, possibly leading to the pathological fatigability lamented by some patients. PMID- 20363184 TI - An ERP study of the processing of response conflict in a dynamic localization task: the role of individual differences in task-appropriate behavior. AB - OBJECTIVE: The study aimed at finding specific conflict-sensitive ERP components in a novel dynamic localization task. It was investigated whether these ERP components are sensitive to individual differences in task-appropriate behavior. METHODS: Forty-four participants performed a localization task employing three differentially conflict-inducing experimental conditions: a frequent standard condition (O=target, X=distractor), a rare conflict condition (S=target, O=distractor), and a rare control condition (S=target, X=distractor). RESULTS: Behavioral data revealed increases of RT and error percent in the conflict condition. Early frequency-sensitive components P3a and fronto-central N2, and late conflict-sensitive components left-central N2, P3b, and CRN were observed. Two groups of participants were selected, those responding fast and accurately, and those responding slowly and inaccurately. Interestingly, the left-central N2 correlate of conflict was observed in the first group, whereas the CRN correlate was observed in the latter group. CONCLUSIONS: Findings suggest that pre-response conflict monitoring is required to successfully complete the task, whereas post response conflict monitoring did not seem to improve performance. SIGNIFICANCE: The present study used a novel dynamic localization task to identify ERP components that were sensitive to response conflict, but differentially predictive of good vs. poor task performance. PMID- 20363185 TI - Popper and P300: can the view ever be falsified that P3 latency is a specific indicator of stimulus evaluation? PMID- 20363186 TI - Characterisation of protracted low-level exposure to uranium in the workplace: A comparison of two approaches. AB - Retrospective estimates of internal doses received by workers in the nuclear industry following intake of radionuclides, based on bioassay data, are a benchmark method in epidemiological studies. Nonetheless, full information relative to thousands of people included in an epidemiological cohort is rarely available, thus implying difficulties to estimate exposure precisely. To evaluate the cumulative exposure to uranium in a cohort of the AREVA NC Pierrelatte plant workers, we compared the epidemiological Job Exposure Matrix (JEM) method with the dosimetric method based on biological monitoring of exposure for 30 workers randomly selected within the cohort. A moderate to strong correlation was observed between the estimators resulting from the two approaches, thereby validating the JEM as a tool that can be used to characterise cumulative exposure to uranium in the cohort. In addition, this study showed that the JEM is a valuable complement to the interpretation of bioassy, (1) in providing information on exposure periods as well as on physical and chemical form of the radionuclides and (2) in compensating for the lack of exposure data regarding the very earliest periods. Combining the two methods may improve the precision in reconstructing cumulative exposure for epidemiological studies. PMID- 20363187 TI - Acute coronary syndromes in indigenous Australians: opportunities for improving outcomes across the continuum of care. AB - BACKGROUND: Amongst a long list of health issues driving the disparity experienced by Indigenous Australians, cardiovascular disease (CVD) remains the primary target. It is the principal cause of death and of excess death among Indigenous people in Australia, and accounts for almost one-third of the life expectancy gap. Most attention has focused on the higher burden of traditional risk factors experienced by Indigenous people to explain CVD disparity. Far less attention has focused on the quality and outcomes of health system performance in explaining these differentials. The CASPA study was a retrospective, mixed methods clinical registry and quality improvement program established in the NT of Australia, focused on the patterns, burdens, provision of care, experience of services, adverse outcomes and their determinants among 492 patients (214 Indigenous and 278 non-Indigenous). RESULTS: Indigenous patients were significantly younger and more likely to have existing CVD risk factors and co morbid chronic disease. During hospitalisation they received similar rates of evidence-based care with the exception of lower rates of diagnostic angiography (36.2% vs. 47.6%, p=0.012), lower rates of in-patient cardiac rehabilitation (8.9% vs. 15.3%, p=0.03) and lower prescription of discharge statin (44.8% vs. 57.8%, p=0.006). Indigenous patients were more likely to die during two years of follow-up (30% vs. 17.8%, p=0.002). Both Indigenous and non-Indigenous patients were similarly under-prescribed evidence based therapy after discharge. Exploratory qualitative examination of the experience of Indigenous patients in Alice Springs identified significant barriers to care across the continuum. CONCLUSION: Improvements in the delivery of known effective therapies will make a significant impact on adverse outcomes in Indigenous and non-Indigenous patients alike. Comprehensive and sustained prospective data collection to compliment system reform is essential to improve outcomes and reduce disparity in CVD outcomes experienced by Indigenous Australians. PMID- 20363188 TI - Cardiovascular disease. PMID- 20363189 TI - Symptom experience in patients with primary brain tumours: a longitudinal exploratory study. AB - PURPOSE: This study was undertaken to further understand the symptom experience and the impact of symptoms in daily life in people treated for brain tumours. METHODS: A qualitative prospective longitudinal design was used with 9 people who were interviewed over 4 time points (soon after diagnosis, 3 months, 6 months and 12-months post-diagnosis), providing 21 interviews in total. RESULTS: Key issues for these participants were ongoing fatigue, memory loss and inability to drive. Fatalistic views about the outcomes of their disease were the norm. Participants made adjustments to their lives to accommodate their functional limitations. These included making home alterations, introducing regular exercise to their lives and using complementary therapies. Their expectations did not always match with the reality of the situation, which made several participants angry and dissatisfied with health care professionals. CONCLUSIONS: Issues of quality of life are paramount in this group of poor prognosis patients, therefore, health professionals should provide preparatory information to patients on what to expect from the illness and its treatments. Health professionals should also assist patients to manage debilitating symptoms such as fatigue and cognitive impairment. PMID- 20363191 TI - Lithium time-to-event trial in amyotrophic lateral sclerosis stops early for futility. PMID- 20363192 TI - Risk factors for renal function impairment in a series of 502 patients born with spinal dysraphisms. AB - OBJECTIVE: To evaluate the risk of renal damage in a large series of patients affected by spinal dysraphism. METHODS: Renal function was studied in 502 spinal dysraphisms treated over the last 25 years in a single center: 283 meningomyelocele (MMC), 90 caudal regression syndrome (CRS) and 129 spinal lipoma (SL) cases. In patients with normal and impaired renal function, we compared congenital renal anomalies, vesicoureteric reflux, bladder voiding pattern and upper tract dilatation, analyzing the results with the Fisher test. RESULTS: Neuropathic bladder was observed in 97% of MMC, 60% of CRS, and 39% of SL cases. There was some degree of renal function impairment in 19 MMC (6.7%), 11 CRS (12%, increased to 20% if considering only neuropathic bladder patients), and two SL (1.5%) cases. Renal agenesis was more frequent in CRS (13%), but was not associated with decreased renal function. Overall, vesicoureteric reflux and upper tract dilatation were more frequent in patients with renal damage. Insufficient bladder voiding was statistically associated with renal damage only in the CRS population. Intermittent catheterization did not represent a protective factor against renal damage in patients able to void without significant residual urine. CONCLUSION: This study has increased our understanding of the prognostic risk factors for renal deterioration. More prospective studies are necessary to confirm these results and correlate treatment with renal outcome. PMID- 20363190 TI - Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. AB - BACKGROUND: In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS. METHODS: We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0.68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389. FINDINGS: At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0.51). The hazard ratio of reaching the primary endpoint was 1.13 (95% CI 0.61-2.07). The study was stopped at the first interim analysis because criterion for futility was met (p=0.78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0.15 (95% CI -0.43 to 0.73, p=0.61). There were no major safety concerns. Falls (p=0.04) and back pain (p=0.05) were more common in the lithium group than in the placebo group. INTERPRETATION: We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS. FUNDING: National Institute of Neurological Disorders and Stroke, ALS Association, and ALS Society of Canada. PMID- 20363193 TI - Commentary on: Biers SM, Malone PS. A critical appraisal of the evidence for improved fertility indices in undescended testes after gonadotrophin-releasing hormone therapy and orchidopexy. J Pediatr Urol. PMID- 20363195 TI - Social predictors of repeat adolescent pregnancy and focussed strategies. AB - This article begins with an overview of teenage pregnancy within a social context. Data are then presented on conceptions and repeat conceptions in teenagers. Social predictors of repeat teenage pregnancy are grouped according to social ecological theory. A brief summary of prevention of teenage pregnancy in general is followed by a detailed analysis of studies of interventions designed to prevent repeat pregnancy that reached specific quality criteria. The results of some systematic reviews show no significant overall effect on repeat pregnancy, whereas others show an overall significant reduction. Youth development programmes are shown in some cases to lower pregnancy rates but in other cases to have no effect or even to increase them. Features of secondary prevention programmes more likely to be successful are highlighted. PMID- 20363194 TI - The role of AIRE polymorphisms in melanoma. AB - Polymorphisms of AIRE, a transcription factor that up-regulates intrathymic expression of tissue-specific antigens including melanoma-associated antigens (MAAs), may variably affect the selection of MAAs-specific thymocytes, generating T-cell repertoires protecting or predisposing individuals to melanoma. We found that AIRE single nucleotide polymorphisms (SNPs) rs1055311, rs1800520 and rs1800522 were significantly more frequent in healthy subjects than in melanoma patients, independently from sex, age and stages of melanoma. The presence of these SNPs was associated with increased frequency of two T-cell clonotypes specific for MAGE-1 linking their protective effect to selection/expansion of MAA specific T cells. Interestingly, mRNA transcribed on the rs1800520 SNP showed increased free energy than the wild type suggesting that its reduced stability may be responsible for the different activity of the polymorphic AIRE molecule. This finding may contribute at identifying subjects with increased risk of developing melanoma or patients with melanoma that may take benefit from immunotherapy. PMID- 20363197 TI - Benchmarks for cystic fibrosis carrier screening: a European consensus document. AB - This paper presents an overview of the conclusions from an international conference convened to address current issues related to the provision of Cystic Fibrosis carrier screening within Europe. Consensus was not aimed at stating whether such a programme should be implemented. Instead the focus was to provide a framework for countries and agencies who are considering or planning its establishment. The general principles and target population of Cystic Fibrosis carrier screening, advantages and disadvantages, health economics, monitoring and future evaluative and research directions were covered. A range of screening strategies have been assessed and compared: pre-conceptional and prenatal screening; individual and couple screening; sequential and simultaneous sampling or testing. Furthermore, technical issues were examined with respect to the choice of the panel of mutations, its detection rate, sensitivity, management of intermediate 'at-risk' couples, screening approach to different populations and ethnic minorities, and assurance of laboratory quality control. The consensus statement also aims to establish the benchmarks for communicating with health care providers, the general public and potential and actual participants before and after the genetic test. PMID- 20363196 TI - Gastrointestinal motility disorders and acupuncture. AB - During the last decades, numerous studies have been performed to investigate the effects and mechanisms of acupuncture or electroacupuncture (EA) on gastrointestinal motility and patients with functional gastrointestinal diseases. A PubMed search was performed on this topic and all available studies published in English have been reviewed and evaluated. This review is organized based on the gastrointestinal organ (from the esophagus to the colon), components of gastrointestinal motility and the functional diseases related to specific motility disorders. It was found that the effects of acupuncture or EA on gastrointestinal motility were fairly consistent and the major acupuncture points used in these studies were ST36 and PC6. Gastric motility has been mostly studied, whereas much less information is available on the effect of EA on small and large intestinal motility or related disorders. A number of clinical studies have been published, investigating the therapeutic effects of EA on a number of functional gastrointestinal diseases, such as gastroesophageal reflux, functional dyspepsia and irritable bowel syndrome. However, the findings of these clinical studies were inconclusive. In summary, acupuncture or EA is able to alter gastrointestinal motility functions and improve gastrointestinal motility disorders. However, more studies are needed to establish the therapeutic roles of EA in treating functional gastrointestinal diseases. PMID- 20363198 TI - Diploe screw anchoring of polymethylmethacrylate in cranial surgery. PMID- 20363199 TI - Correction of nipple inversion using a micro-knife and transverse to longitudinal skin closure. AB - Through a series of 7 patients (8 nipples), we present a technique for the correction of nipple inversion. We use a micro-knife to divide the shortened ducts and fibrous tissues, as well as an internal cerclage suture and reverse strictureplasty skin closure to effectively correct and maintain the position of the inverted nipple. The advantages of the proposed technique include its simplicity, effectiveness in severe cases, and long-lasting results. PMID- 20363200 TI - Has pay for performance improved the management of diabetes in the United Kingdom? AB - Over the past decade the UK government has introduced a number of major policy initiatives to improve the quality of health care. One such initiative was the introduction of the Quality and Outcomes Framework (QOF), a pay for performance scheme launched in April 2004, which aims to improve the primary care management of common chronic conditions including diabetes. Some evidence suggest that introduction of QOF has been associated with improvements in the quality indicators for diabetes care included in the framework. However, it is difficult to disentangle the impact of QOF from other quality initiatives as few studies adjusted for underlying trends in quality. There is some evidence that QOF may have reduced inequalities in diabetes care between affluent and deprived areas but women and individuals from ethnic minority groups appear to have benefited least from this initiative. Less is known about the impact of QOF on aspects of diabetes care not reflected in the framework, including self-management and continuity of care. PMID- 20363201 TI - Generation of induced pluripotent stem cells from newborn marmoset skin fibroblasts. AB - Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine. For the application of iPSCs to forms of autologous cell therapy, suitable animal models are required. Among species that could potentially be used for this purpose, nonhuman primates are particularly important, and among these the marmoset offers significant advantages. In order to demonstrate the feasibility of the application of iPSC technology to this species, here we derived lines of marmoset iPSCs. Using retroviral transduction with human Oct4, Sox2, Klf4 and c-Myc, we derived clones that fulfil critical criteria for successful reprogramming: they exhibit typical iPSC morphology; they are alkaline phosphatase positive; they express high levels of NANOG, OCT4 and SOX2 mRNAs, while the corresponding vector genes are silenced; they are immunoreactive for Oct4, TRA-1-81 and SSEA-4; and when implanted into immunodeficient mice they produce teratomas that have derivatives of all three germ layers (endoderm, alpha fetoprotein; ectoderm, betaIII-tubulin; mesoderm, smooth muscle actin). Starting with a population of 4 x 10(5) newborn marmoset skin fibroblasts, we obtained approximately 100 colonies with iPSC-like morphology. Of these, 30 were expanded sufficiently to be cryopreserved, and, of those, 8 were characterized in more detail. These experiments provide proof of principle that iPSC technology can be adapted for use in the marmoset, as a future model of autologous cell therapy. PMID- 20363202 TI - Up-scaling single cell-inoculated suspension culture of human embryonic stem cells. AB - We have systematically developed single cell-inoculated suspension cultures of human embryonic stem cells (hESC) in defined media. Cell survival was dependent on hESC re-aggregation. In the presence of the Rho kinase inhibitor Y-27632 (Ri) only approximately 44% of the seeded cells were rescued, but an optimized heat shock treatment combined with Ri significantly increased cell survival to approximately 60%. Mechanistically, our data suggest that E-cadherin plays a role in hESC aggregation and that dissociation and re-aggregation upon passaging functions as a purification step towards a pluripotency markers-enriched population. Mass expansion of hESC was readily achieved by up-scaling 2 ml cultures to serial passaging in 50 ml spinner flasks. A media comparison revealed that mTeSR was superior to KnockOut-SR in supporting cell proliferation and pluripotency. Persistent expression of pluripotency markers was achieved for two lines (hES2, hES3) that were used at higher passages (>86). In contrast, rapid down regulation of Oct4, Tra-1-60, and SSEA4 was observed for ESI049, a clinically compliant line, used at passages 20-36. The up-scaling strategy has significant potential to provide pluripotent cells on a clinical scale. Nevertheless, our data also highlights a significant line-to-line variability and the need for a critical assessment of novel methods with numerous relevant cell lines. PMID- 20363203 TI - Non-steroidal anti-inflammatory drugs for athletes: an update. AB - Sports medicine physicians often treat athletes in pain with non-steroidal anti inflammatory drugs (NSAIDs). However, there is a lack of high-quality evidence to guide NSAID use. Their adverse effects have clinical relevance, and their possible negative consequences on the long-term healing process are slowly becoming more obvious. This article provides some practical management guidelines for the use of NSAIDs, developed to help sports medicine physicians deal with frequent sports-related injuries. We do not recommend their use for muscle injuries, bone fractures (also stress fractures) or chronic tendinopathy. In all cases, if chosen, NSAID treatments should always be kept as short as possible and should take into account the specific type of injury, the level of dysfunction and pain. PMID- 20363204 TI - Tensile bond strength of cast commercially pure titanium dowel and cores cemented with three luting agents. AB - PURPOSE: The purpose of this study was to compare the tensile strength of commercially pure titanium dowels and cores cemented with zinc phosphate or resin cements. METHODS: Twenty-one extracted human canines were endodontically treated. The root preparations were accomplished using Largo reamers (10mm in depth and 1.7 mm in diameter). Acrylic resin patterns for the dowel and cores were made, and specimens were cast in commercially pure titanium (n=7) and divided in three groups: TZ-CP Ti dowels luted with zinc phosphate luting agent, TP-CP Ti dowels luted with Panavia F and TR-CP Ti dowels luted with RelyX U100. Tensile strengths were measured in a universal testing machine at a crosshead speed of 0.5mm/min. The results (N) were statistically analyzed by ANOVA and Tukey tests (alpha=0.01). RESULTS: The ANOVA indicated that there were significant differences among the groups tested. A Tukey multiple comparison procedure was performed and revealed statistically significant higher retention values for the dowel luted with RelyX U100 when compared with zinc phosphate or Panavia F. CONCLUSION: Cast commercially pure titanium dowels and cores fixed with RelyX U100 cement presented superior bond strength retention when compared to zinc phosphate and Panavia F. PMID- 20363205 TI - Ancient dicrocoeliosis: Occurrence, distribution and migration. AB - This paper focuses on the lancet fluke, Dicrocoelium sp., and includes a complete review of the literature as well as numerous new research results. The compilation of all these data led to a global overview of ancient dicrocoeliosis history. The presence of the lancet fluke in Western Europe was attested from 550,000 years BP to the 16th century AD Moreover, the parasite was identified in the New World around the 17th century AD following the colonization of Canada by Europeans. The role of human and animal migrations is discussed. PMID- 20363207 TI - A PCR-after-ligation method for cloning of multiple DNA inserts. AB - Here we present a novel and simple PCR-after-ligation method for efficient assembly of multiple DNA inserts. After initial ligation of multiple inserts and vector, the ligation mixture is used as template for a PCR using a pair of primers flanking the cloning sites on the vector. The fragment with correct size is gel purified and inserted into the vector by conventional two-way ligation. With this method, a recombinant plasmid containing four DNA inserts was correctly constructed. As a control, all of the constructs obtained directly from DNA ligation were found to be self-ligation of the vector. PMID- 20363208 TI - Development of a microfluidic chip-based plasmid miniprep. AB - Plasmids are the workhorse of contemporary molecular biology, serving as vectors in the multitude of molecular cloning approaches now available. Plasmid minipreps are a routine and essential means of extracting plasmid DNA from bacteria, such as Escherichia coli, for identification, characterization, and further manipulation. Although there have been many approaches described and miniprep kits are commercially available, traditional minipreps typically require more than 16h, including the time needed for bacterial cell culture. Here we describe the development of a microfluidic chip (MFC)-based miniprep that uses on-chip lysis and trapping of large DNA in agarose to differentially separate plasmid DNA from the bacterial chromosome. Our approach greatly decreases both the time required for the miniprep itself and the time required for growth of the bacterial cultures because our on-chip miniprep uses 10(5) times fewer E. coli cells. Because the quality of the isolated plasmid is comparable to that obtained using conventional miniprep protocols, this approach allows growth of E. coli and isolation of plasmid within hours, thereby making it ideal for rapid screening approaches. This MFC-based miniprep, coupled with recently demonstrated on-chip transfection capabilities, lays the groundwork for seamless manipulation of plasmids on MFC platforms. PMID- 20363206 TI - Recognition of decay accelerating factor and alpha(v)beta(3) by inactivated hantaviruses: Toward the development of high-throughput screening flow cytometry assays. AB - Hantaviruses cause two severe diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The lack of vaccines or specific drugs to prevent or treat HFRS and HCPS and the requirement for conducting experiments in a biosafety level 3 laboratory (BSL-3) limit the ability to probe the mechanism of infection and disease pathogenesis. In this study, we developed a generalizable spectroscopic assay to quantify saturable fluorophore sites solubilized in envelope membranes of Sin Nombre virus (SNV) particles. We then used flow cytometry and live cell confocal fluorescence microscopy imaging to show that ultraviolet (UV)-killed SNV particles bind to the cognate receptors of live virions, namely, decay accelerating factor (DAF/CD55) expressed on Tanoue B cells and alpha(v)beta(3) integrins expressed on Vero E6 cells. SNV binding to DAF is multivalent and of high affinity (K(d) approximately 26pM). Self-exchange competition binding assays between fluorescently labeled SNV and unlabeled SNV are used to evaluate an infectious unit-to-particle ratio of approximately 1:14,000. We configured the assay for measuring the binding of fluorescently labeled SNV to Tanoue B suspension cells using a high-throughput flow cytometer. In this way, we established a proof-of-principle high-throughput screening (HTS) assay for binding inhibition. This is a first step toward developing HTS format assays for small molecule inhibitors of viral-cell interactions as well as dissecting the mechanism of infection in a BSL-2 environment. PMID- 20363209 TI - Reference gene selection for real-time quantitative polymerase chain reaction normalization in "Swingle" citrumelo under drought stress. AB - We describe the first systematic evaluation of reference genes for use in real time quantitative polymerase chain reaction (qPCR) for water deficit stress studies in the citrus rootstock "Swingle" citrumelo. The expression levels of seven reference genes-cyclophilin (CYP), cathepsin (CtP), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), elongation factor 1alpha (EF1alpha), beta-tubulin (TUB), and ADP ribosylation factor (ADP)-during drought stress were tested using geNorm and NormFinder programs. Results from four experimental conditions indicated that EF1alpha and ADP were the most stable reference genes. Relative expression levels of Delta1-pyrroline-5-carboxylate synthetase (P5CS) was used for reference gene validation. PMID- 20363210 TI - The hidden face of food phenolic composition. AB - Plant polyphenols are extremely diverse, due to the occurrence of several basic structures, numerous substitutions and, for some groups, of polymers (tannins). Plant polyphenol composition depends on the plant species and organ, with some molecules specific of particular plant families while others are ubiquitous. The polyphenol content is classically assessed by global analysis methods, which lack specificity and accuracy. These methods have been replaced with high performance liquid chromatography (HPLC), that enables accurate determination of individual molecules, provided they can be unambiguously identified and calibration curves can be established. However, HPLC analysis is restricted to simple compounds and difficult to apply in the case of complex extracts. Further difficulties encountered in the case of polymers include irreversible adsorption on the stationary phases. Proanthocyanidin analysis by HPLC after acid-catalysed depolymerisation in the presence of a nucleophile permits to overcome these problems and shows that proanthocyanidins predominate in the polyphenol composition of most plants. Large varietal differences in tannin quantitative and qualitative composition were observed for all plant species studied. Moreover, analysis is usually performed after extraction, which may lead to significant underestimation of the polyphenol content, since a large proportion is not extracted by usual solvents. This may be due to covalent binding to other plant constituents and to non-covalent adsorption on plant solids. Such matrix effect also influences the taste perception of polyphenols and their fate in the digestive tract, from in-mouth interactions with salivary proteins to their metabolism by colon microflora, with potential influence on bioavailability. PMID- 20363211 TI - The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice. AB - CagA protein is the most assessed effecter molecule of Helicobacter pylori. In this report, we demonstrate how CagA protein regulates the functions of dendritic cells (DC) against H. pylori infection. In addition, we found that CagA protein was tyrosine-phosphorylated in DC. The responses to cagA-positive H. pylori in DC were reduced in comparison to those induced by cagA-negative H. pylori. CagA overexpressing DC also exhibited a decline in the responses against LPS stimulation and the differentiation of CD4(+) T cells toward Th1 type cells compared to wild type DC. In addition, the level of phosphorylated IRF3 decreased in CagA-overexpressing DC stimulated with LPS, indicating that activated SHP-2 suppressed the enzymatic activity of TBK1 and consequently IRF3 phosphorylation. These data suggest that CagA protein negatively regulates the functions of DC via CagA phosphorylation and that cagA-positive H. pylori strains suppress host immune responses resulting in their chronic colonization of the stomach. PMID- 20363212 TI - The secretory pathway Ca(2+)-ATPase 1 is associated with cholesterol-rich microdomains of human colon adenocarcinoma cells. AB - Lipid rafts are often considered as microdomains enriched in sphingomyelin and cholesterol, predominantly residing in the plasma membrane but which originate in earlier compartments of the cellular secretory pathway. Within this pathway, the membranes of the Golgi complex represent a transition stage between the cholesterol-poor membranes of the endoplasmic reticulum (ER) and the cholesterol rich plasma membrane. The rafts are related to detergent-resistant membranes, which because of their ordered structure are poorly penetrated by cold non-ionic detergents and float in density gradient centrifugation. In this study the microdomain niche of the Golgi-resident SPCA Ca(2+)/Mn(2+) pumps was investigated in HT29 cells by Triton X-100 detergent extraction and density-gradient centrifugation. Similarly to cholesterol and the raft-resident flotillin-2, SPCA1 was found mainly in detergent-resistant fractions, while SERCA3 was detergent soluble. Furthermore, cholesterol depletion of cells resulted in redistribution of flotillin-2 and SPCA1 to the detergent-soluble fractions of the density gradient. Additionally, the time course of solubilization by Triton X-100 was investigated in live COS-1 and HT29 cells expressing fluorescent SERCA2b, SPCA1d or SPCA2. In both cell types, the ER-resident SERCA2b protein was gradually solubilized, while SPCA1d resisted to detergent solubilization. SPCA2 was more sensitive to detergent extraction than SPCA1d. To investigate the functional impact of cholesterol on SPCA1, ATPase activity was monitored. Depletion of cholesterol inhibited the activity of SPCA1d, while SERCA2b function was not altered. From these results we conclude that SPCA1 is associated with cholesterol rich domains of HT29 cells and that the cholesterol-rich environment is essential for the functioning of the pump. PMID- 20363213 TI - Post-translational modification of TRAIL receptor type 1 on various tumor cells and the susceptibility of tumors to TRAIL-induced apoptosis. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R1 and TRAIL-R2) are promising targets for tumor therapy. However, their clinical use is limited because some tumors show resistance to TRAIL-treatment. Here, we analyzed epitopes of nine TRAIL-R1-specific human monoclonal antibodies and demonstrated at least five tentative epitopes on human TRAIL-R1. We found that some of the five were post-translationally modified on some tumor cell lines. Interestingly, one of them, an epitope of TR1-272 antibody (TR1-272 epitope) disappeared on the tumor cells that are more susceptible to TRAIL induced apoptosis compared to TR1-272-epitope positive cells. Treatment of TR1 272-epitope negative cells with TRAIL induced large cluster formation of TRAIL R1, while treatment of TR1-272-epiope positive cells with TRAIL did not. These results suggest that TR1-272-antibody might distinguish the TRAIL-R1 conformation that could deliver stronger death signals. Further analysis of epitope-appearance and sensitivity to TRAIL should clarify the mechanisms of TRAIL-induced apoptosis of tumor cells and would provide useful information about tumor therapy using TRAIL and TRAIL-R signaling. PMID- 20363214 TI - Urocortins in heart failure. AB - Despite modern advances in the treatment of the causes and consequences of cardiovascular illness, heart disease and heart failure remain a leading cause of death in the western world. Many novel peptides are emerging as biomarkers and potential therapeutic tools for this debilitating condition. Urocortins represent one such group of peptides whose role in normal cardiovascular physiology and disease states is now increasingly being recognized. The cardiovascular effects of the urocortins are mediated via corticotrophin-releasing hormone (CRH) receptors through a variety of intra-cellular signaling pathways. Studies to date have demonstrated a favourable effect of urocortins on hemodynamic and neurohumoral regulation. They cause relaxation of the vasculature as well as having positive inotropic, chronotropic and lusitropic effects on the heart. This makes the urocortins a potentially attractive target in the treatment of heart failure. Indeed, a number of studies have demonstrated increased urocortin activity in experimental and clinical heart failure, with apparent augmented responses in these states. This article provides a review of the role of urocortins in normal cardiovascular physiology and in the pathophysiology of heart failure. PMID- 20363215 TI - Functional characterization of gefitinib uptake in non-small cell lung cancer cell lines. AB - Gefitinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, has been developed and approved for treatment of advanced non-small cell lung cancer (NSCLC). In this study, we investigated the uptake of gefitinib in gefitinib sensitive and -resistant NSCLC cell lines. The transport system was temperature dependent, indicative of an active process and sodium- and potential-independent. Moreover, high cell densities and low extracellular pH significantly reduced the uptake of gefitinib. Inhibitors of the human organic cation transporter 1 (hOCT1) significantly decreased gefitinib uptake; however, gefitinib was not a substrate for hOCT1 or hOCT2 in overexpressing HEK293 cells. Interestingly, gefitinib significantly reduced uptake of the hOCT prototypical substrate MPP suggesting that gefitinib may exert an inhibitory effect on the intracellular accumulation of drugs transported by hOCT1 and hOCT2. After 15min of treatment at 1microM (the maximum plasma concentration of gefitinib obtained at the clinically relevant dose) gefitinib accumulated within the cell in resistant-cell lines at concentrations similar or even higher than in gefitinib-sensitive cells tending to rule out an alteration in drug uptake as a mechanism of resistance to gefitinib treatment. Moreover, our results suggest that the extrusion of lactate by crowded cells may contribute in decreasing the pH, which in turn can influence the uptake of gefinitib and as a result the inhibition of EGFR autophosphorylation. PMID- 20363216 TI - Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. AB - Diabetes mellitus is a chronic metabolic disorder affecting about 6% of population worldwide with its complications and is rapidly reaching epidemic scale. Cinnamomum zeylanicum is widely used in alternative system of medicine for treatment of diabetes. In the present study, we have performed bioassay guided fractionation of chloroform extract of C. zeylaniucm and identified cinnamaldehyde (CND) as an active principle against diabetes. In continuation to it, a detailed study was undertaken to elucidate its mode of antidiabetic action in STZ induced diabetic rats. Oral administration of CND (20 mg/kg bw) to diabetic rats for 2 months showed significant improvement (p<0.001) in muscle and hepatic glycogen content. In vitro incubation of pancreatic islets with CND enhanced the insulin release compared to glibenclamide. The insulinotropic effect of CND was found to increase the glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues. The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels. Furthermore, the median lethal dose (LD(50)) of CND could not be obtained even at 20 times (0.4 g/kg bw) of its effective dose. With the high margin of safety of CND, it can be developed as a potential therapeutic candidate for the treatment of diabetes. PMID- 20363217 TI - Robustness of positional specification by the Hedgehog morphogen gradient. AB - Spatial gradients of Hedgehog signalling play a central role in many patterning events during animal development, regulating cell fate determination and tissue growth in a variety of tissues and developmental stages. Experimental evidence suggests that many of the proteins responsible for regulating Hedgehog signalling and transport are themselves targets of Hedgehog signalling, leading to multiple levels of feedback within the system. We use mathematical modelling to analyse how these overlapping feedbacks combine to regulate patterning and potentially enhance robustness in the Drosophila wing imaginal disc. Our results predict that the regulation of Hedgehog transport and stability by glypicans, as well as multiple overlapping feedbacks in the Hedgehog response network, can combine to enhance the robustness of positional specification against variability in Hedgehog levels. We also discuss potential trade-offs between robustness and additional features of the Hedgehog gradient, such as signalling range and size regulation. PMID- 20363218 TI - Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats. AB - Nicotine was reported to reduce the plaque burden and could be used as a possible anti-Alzheimer's disease agent. However, the effect of nicotine on memory and tau pathology in Alzheimer's disease has been less studied. The present study investigated the effect of nicotine on tau phosphorylation and cognitive impairment induced by hippocampus injections of amyloid-beta (Abeta) 25-35. Rats were treated with nicotine hydrogen tartrate salt dissolved in normal saline by subcutaneous injection twice per day for 14 days. The age and gender matched rats treated with same amount of normal saline were used as the control. Morris water maze was used to detect the cognitive impairment induced by Abeta25-35. Compared to the sham-operated rats, Abeta25-35 injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test and increased the number of tau(pS202) and tau(pT231) immunoreactive cells. The data show that nicotine (1mg/kg in base weight) treatment significantly exacerbates cognitive impairment and tau phosphorylation at Ser-202 and Thr-231 in the hippocampus compared with Abeta25-35 injection groups in the Abeta rat model of Alzheimer's disease. The use of nicotine for treatment of Alzheimer's disease should be reassessed. PMID- 20363220 TI - Editorial for special issue on mGluRs and cognition. PMID- 20363219 TI - Metabotropic glutamate receptor subtype 5 antagonism in learning and memory. AB - The role of the metabotropic glutamate receptor 5 (mGlu(5) receptor) in learning and memory and other behaviors are reviewed by examining the influence of selective antagonists and genetic knockout on performance. This receptor is involved in spatial learning, contextual fear conditioning, inhibitory avoidance, fear potentiated startle, and conditioned taste aversion. However, mGlu(5) receptor antagonists have proven to be ineffective in other learning tasks, such as the delayed-match-to-position test and a three-hole spatial learning task. Locomotion is often decreased by mGlu(5) receptor antagonists; and other behaviors such as social interaction and consummatory responses can also be affected. In mGlu(5) receptor knockout mice, performance in contextual fear conditioning and spatial water maze tasks is impaired. Although the available evidence is suggestive of an important contribution of mGlu(5) receptors to cognitive functions, further studies are needed, particularly those with in vivo evaluation of the role of mGlu(5) receptors in selective brain regions in different stages of memory formation. PMID- 20363222 TI - Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons. AB - Reactive oxygen species (ROS) can trigger neuronal cell death and has been implicated in a variety of neurodegenerative diseases as well as brain ischemia. Here, we demonstrate that chronic (but not acute) glutamate toxicity in primary cortical neuronal cultures is associated with hydrogen peroxide (H(2)O(2)) accumulation in the culture medium and that neurotoxicity can be eliminated by external catalase treatment. Neuronal cultures in Ca(2+)-free medium or treated with BAPTA showed reduced glutamate-induced H(2)O(2) generation, indicating that H(2)O(2) generation is Ca(2+)-dependent. Pharmacological and genetic approaches revealed that NADPH oxidase plays a role in glutamate-induced H(2)O(2) generation and that activation of NMDA and AMPA receptors is involved in this H(2)O(2) generation. The Nox4 siRNA reduced NMDA-induced H(2)O(2) production by 54% and cytotoxicity in parallel, suggesting that Nox4-containing NADPH oxidase functions NMDA receptor-mediated H(2)O(2) production resulting in neurotoxicity. These findings suggest that the modulation of NADPH oxidase can be used as a new therapeutic strategy for glutamate-induced neuronal diseases. PMID- 20363221 TI - alpha1-Acid glycoprotein production in rat dorsal air pouch in response to inflammatory stimuli, dexamethasone and honey bee venom. AB - This study shows the rapid and differential production of the 40-43 kDa and the 70-90 kDa alpha1-acid glycoprotein (AGP) fucosylated glycoforms after treatment of the dorsal air pouch with bacterial lipopolysaccharide (LPS), HgCl(2) or Freund's complete adjuvant (FCA). The 40-43 kDa and the 70-90 kDa AGP production is peaked 1-3 h post-LPS treatment. We observed that the responses to LPS and FCA are similar in that both AGP isoforms are induced whereas they differ in that the FCA exhibits a 6 h lag period. The response to HgCl(2,) however, exhibits the specific biphasic induction only of the 40-43 kDa AGP. The serum 40-43 kDa AGP glycoform gradually increases in response to all of the above stimulants and peaks by 24 h post- treatment. The increase of the 70-90 kDa AGP levels in the air pouch occurs in association with the accumulation of polymorphonuclear (PMN) cells while dexamethasone (DEX) increases only the 40-43 kDa AGP production in the absence of PMN accumulation. Macrophage-monocyte lineage cells forming the air pouch lining tissue may potentially be the cells that secrete the 40-43 kDa AGP while polymorphonuclear cells that infiltrate the air pouch secrete the 70-90 kDa AGP. The 40-43 kDa and 70-90 kDa AGP production induced by LPS in the air pouch precedes that of interleukin-1 (IL-1) or interleukin-6 (IL-6) while the 40 43 kDa AGP glycoform potentially increases IL-6 production by air pouch PMN exudate cells. These significant differences suggest a local pro-inflammatory role of AGP. Honeybee venom suppressed arthritis development and exhibited differential local or systemic regulation of AGP in serum vs. air pouch exudate or synovial fluid. This study with the air pouch model of facsimile synovium tissue suggests that local alpha1-acid glycoprotein (AGP) production may contribute to pro-inflammatory and anti-inflammatory activities during the local acute phase response or during chronic inflammatory stress as in arthritis. PMID- 20363223 TI - Development and validation of a high throughput direct radioimmunoassay for the quantitative determination of serum and plasma melatonin (N-acetyl-5 methoxytryptamine) in mice. AB - A simple, sensitive and specific high throughput radioimmunoassay (RIA) for the quantitative determination of total melatonin (N-acetyl-5-methoxytryptamine) was developed. This method allows the analysis of melatonin in different biological fluids with small sample volumes (e.g. mice and rats), and wide working range. With the preparation of matrix-specific calibrators called "Equalizing Reagent" the influence of results due to different composition between standards and sample matrix was reduced. This reagent is produced by use of the respective biological liquid. Endogenous melatonin is removed by adsorption to activated charcoal. The melatonin-free biological liquid is then used to equalize the assay matrix of standards and untreated samples. Finally, all samples including the standards are digested by use of a protease to reduce non-specific binding, for example to albumin or albumin-like molecules. High-affinity specific antibodies were produced by immunization of rabbits with 5-methoxytryptamine-bovine serum albumin. The review of cross reactions to ten structurally similar compounds showed that the antibody has a high specificity for melatonin. This direct RIA uses a [(125)I]-melatonin tracer for the determination of melatonin. 5 methoxytryptamine was synthesized by direct iodination with [(125)I]-Bolton Hunter-Reagent. The required acceptance criteria for validation parameters were fulfilled. The flexible standards cover a working range from 12 to 4000 pg/mL with a sample volume of 50 microL (e.g. working range from 3 to 1000 pg/mL with a sample volume of 200 microL). The limit of detection in mouse serum and mouse plasma was 9 pg/mL and 7 pg/mL, respectively. The recovery of melatonin in mouse serum was 108% and in mouse plasma 99%. The variation coefficients of the assay, within and between runs, ranged between 7 and 13% in mouse serum and between 5 and 8% in mouse plasma. Based on the determination of a 24-h profile of melatonin in mouse samples a characteristic diurnal rhythm of melatonin was observed. The wide working range makes it possible to analyse low and high melatonin concentrations. The validated direct RIA was compared with established sample preparation methods such as liquid-liquid- and solid-phase-extraction followed by RIA. The correlation for methanol extraction is y=1.1x-0.9, R(2)=0.98, P<0.001 and C(18)-extraction y=0.8x-0.03, R(2)=0.99, P<0.001. The distinct advantage of the direct assay of melatonin is that complicated extraction steps can be avoided. The realized advantages of the direct RIA when compared to a commercially available melatonin RIA are its low sample volume and ease of implementation. Exemplary, plasma melatonin was determined at C3H, C57BL, wild type and melatonin receptor (MT1-/- and MT2-/-) knockout mice kept under L:D=12:12 cycles. The results have indicated that at all mouse strains have plasma melatonin content, with higher levels during the night and lower levels during the day. Because of different melatonin concentrations the direct RIA convince by its low detection limit and wide working range. The determination of serum and plasma melatonin in mice by ELISA or HPLC-technique previously failed due to the required use of a high sample volume and the low sensitivity. In summary, it can be concluded that the developed and validated direct RIA meets the requirements for the determination of melatonin and is especially suitable for the analysis of melatonin in different mouse strains. PMID- 20363224 TI - An extended antibody microarray for surface profiling metastatic melanoma. AB - An antibody microarray was developed for profiling the surface proteome of melanoma cells, which may facilitate melanoma sub-classification and provide important prognostic information useful in predicting the clinical behavior of the melanoma (e.g., likely sites of metastatic spread), patient outcome and treatment response. Forty-eight antibodies were selected based on their correlation with melanoma development, progression and/or prognosis and printed on nitrocellulose slides. The immobilised antibodies capture live cells expressing corresponding antigens to produce a cell binding dot pattern representing the surface antigen profile (immunophenotype) of the melanoma. Surface antigen signatures were determined for a normal melanocyte and 6 melanoma cell lines and cell suspensions prepared from 10 surgically excised melanoma lymph node metastases. A procedure for obtaining separate surface antigen profiles for melanoma cells and leukocytes from clinical lymph node samples was also developed using anti-CD45 magnetic beads. The capture of live, bead-bound leukocytes on these antibody microarrays provides a significant enhancement of this microarray technology. The antibody microarray will be used to profile panels of surgically excised melanoma lymph node metastases (melanoma and leukocyte fractions) to determine whether the immunophenotypes correlate with clinicopathological characteristics, disease progression and clinical outcome. PMID- 20363225 TI - Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model. AB - We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/ 0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis. PMID- 20363226 TI - An archaeal Dim2-like protein, aDim2p, forms a ternary complex with a/eIF2 alpha and the 3' end fragment of 16S rRNA. AB - Dim2p is a eukaryal small ribosomal subunit RNA processing factor required for the maturation of 18S rRNA. Here we show that an archaeal homolog of Dim2p, aDim2p, forms a ternary complex with the archaeal homolog of eIF2 alpha, a/eIF2 alpha, and the RNA fragment that possesses the 3' end sequence of 16S rRNA both in solution and in crystal. The 2.8-A crystal structure of the ternary complex reveals that two KH domains of aDim2p, KH-1 and -2, are involved in binding the anti-Shine-Dalgarno core sequence (CCUCC-3') and a highly conserved adjacent sequence (5'-GGAUCA), respectively, of the target rRNA fragment. The surface plasmon resonance results show that the interaction of aDim2p with the target rRNA fragment is very strong, with a dissociation constant of 9.8 x 10(-10) M, and that aDim2p has a strong nucleotide sequence preference for the 3' end sequence of 16S rRNA. On the other hand, aDim2p interacts with the isolated alpha subunit and the intact alpha beta gamma complex of a/eIF2, irrespective of the RNA binding. These results suggest that aDim2p is a possible archaeal pre-rRNA processing factor recognizing the 3' end sequence (5'-GAUCACCUCC-3') of 16S rRNA and may have multiple biological roles in vivo by interacting with other proteins such as a/eIF2 and aRio2p. PMID- 20363227 TI - Structure-based design of a photocontrolled DNA binding protein. AB - Photocontrolled transcription factors could be powerful tools for probing the role of transcriptional processes in settings that are spatially or temporally complex. We report the structure-based design of a photocontrolled bZIP-type DNA binding protein that is a hybrid of the prototypical homodimeric bZIP protein GCN4 and photoactive yellow protein (PYP), a blue-light-sensitive protein from Halorhodospira halophila. A fusion of the C-terminal zipper region of GCN4-bZIP with the N-terminal cap of PYP was designed based on examination of available crystal structure data, analysis of amino acid preference rules for leucine zippers, and mutational and amino acid conservation data for PYP, together with Rosetta-guided structural modeling. The designed fusion protein GCN4Delta25PYP-v2 is monomeric in the dark; fluorescence, circular dichroism, NMR, and analytical ultracentrifugation data indicate that the zipper domain is hidden. DNA binding in the dark causes substantial structural reorganization of GCN4Delta25PYP-v2 with concomitant slowing of the photocycle, consistent with conformational coupling of the DNA binding domain and the light-sensitive domain of the protein. Consistent with this finding, blue-light irradiation causes a 2-fold increase in specific DNA binding affinity that reverses in the dark. The structure-based approach suggests strategies for enhancing this activity and for producing a family of related photocontrolled proteins for manipulating bZIP activity. PMID- 20363228 TI - Computational and experimental evidence for the evolution of a (beta alpha)8 barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds. AB - The evolution of the prototypical (beta alpha)(8)-barrel protein imidazole glycerol phosphate synthase (HisF) was studied by complementary computational and experimental approaches. The 4-fold symmetry of HisF suggested that its constituting (beta alpha)(2) quarter-barrels have a common evolutionary origin. This conclusion was supported by the computational reconstruction of the HisF sequence of the last common ancestor, which showed that its quarter-barrels were more similar to each other than are those of extant HisF proteins. A comprehensive sequence analysis identified HisF-N1 [corresponding to (beta alpha)(1-2)] as the slowest evolving quarter-barrel. This finding indicated that it is the closest relative of the common (beta alpha)(2) predecessor, which must have been a stable and presumably tetrameric protein. In accordance with this prediction, a recombinantly produced HisF-N1 protein was properly folded and formed a tetramer being stabilised by disulfide bonds. The introduction of a disulfide bond in HisF-C1 [corresponding to (beta alpha)(5-6)] also resulted in the formation of a stable tetramer. The fusion of two identical HisF-N1 quarter barrels yielded the stable dimeric half-barrel HisF-N1N1. Our findings suggest a two-step evolutionary pathway in which a HisF-N1-like predecessor was duplicated and fused twice to yield HisF. Most likely, the (beta alpha)(2) quarter-barrel and (beta alpha)(4) half-barrel intermediates on this pathway were stabilised by disulfide bonds that became dispensable upon consolidation of the (beta alpha)(8) barrel. PMID- 20363229 TI - A single-amino-acid substitution in the C terminus of PhoP determines DNA-binding specificity of the virulence-associated response regulator from Mycobacterium tuberculosis. AB - The Mycobacterium tuberculosis PhoP-PhoR two-component system is essential for virulence in animal models of tuberculosis. Genetic and biochemical studies indicate that PhoP regulates the expression of more than 110 genes in M. tuberculosis. The C-terminal effector domain of PhoP exhibits a winged helix-turn helix motif with the molecular surfaces around the recognition helix (alpha 8) displaying strong positive electrostatic potential, suggesting its role in DNA binding and nucleotide sequence recognition. Here, the relative importance of interfacial alpha 8-DNA contacts has been tested through rational mutagenesis coupled with in vitro binding-affinity studies. Most PhoP mutants, each with a potential DNA contacting residue replaced with Ala, had significantly reduced DNA binding affinity. However, substitution of nonconserved Glu215 had a major effect on the specificity of recognition. Although lack of specificity does not necessarily correlate with gross change in the overall DNA binding properties of PhoP, structural superposition of the PhoP C-domain on the Escherichia coli PhoB C-domain-DNA complex suggests a base-specific interaction between Glu215 of PhoP and the ninth base of the DR1 repeat motif. Biochemical experiments corroborate these results, showing that DNA recognition specificity can be altered by as little as a single residue change of the protein or a single base change of the DNA. The results have implications for the mechanism of sequence-specific DNA binding by PhoP. PMID- 20363230 TI - Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL. AB - Interactions among Bcl-2 family proteins are important for regulating apoptosis. Prosurvival members of the family interact with proapoptotic BH3 (Bcl-2-homology 3)-only members, inhibiting execution of cell death through the mitochondrial pathway. Structurally, this interaction is mediated by binding of the alpha helical BH3 region of the proapoptotic proteins to a conserved hydrophobic groove on the prosurvival proteins. Native BH3-only proteins exhibit selectivity in binding prosurvival members, as do small molecules that block these interactions. Understanding the sequence and structural basis of interaction specificity in this family is important, as it may allow the prediction of new Bcl-2 family associations and/or the design of new classes of selective inhibitors to serve as reagents or therapeutics. In this work, we used two complementary techniques- yeast surface display screening from combinatorial peptide libraries and SPOT peptide array analysis--to elucidate specificity determinants for binding to Bcl x(L)versus Mcl-1, two prominent prosurvival proteins. We screened a randomized library and identified BH3 peptides that bound to either Mcl-1 or Bcl-x(L) selectively or to both with high affinity. The peptides competed with native ligands for binding into the conserved hydrophobic groove, as illustrated in detail by a crystal structure of a specific peptide bound to Mcl-1. Mcl-1 selective peptides from the screen were highly specific for binding Mcl-1 in preference to Bcl-x(L), Bcl-2, Bcl-w, and Bfl-1, whereas Bcl-x(L)-selective peptides showed some cross-interaction with related proteins Bcl-2 and Bcl-w. Mutational analyses using SPOT arrays revealed the effects of 170 point mutations made in the background of a peptide derived from the BH3 region of Bim, and a simple predictive model constructed using these data explained much of the specificity observed in our Mcl-1 versus Bcl-x(L) binders. PMID- 20363231 TI - Energetics of breath-hold hunting: modeling the effects of aging on foraging success in the Weddell seal. AB - A simulation model was developed to predict age-related changes in foraging energetics of individual Weddell seals, Leptonychotes weddellii. Aging in diving animals is interesting because their characteristic cyclic sequence of apneustic hunting and eupnea should elevate oxidative stress, possibly accelerating aging. Such a hypothesis can be evaluated by modeling energetics of constrained, time partitioned activities with well-defined costs. Three possible consequences of physiological aging in divers were specified and appraised. The model examined the potential impacts of age-related decline in muscle contractile ability, increased buoyancy, and reduced aerobic dive limit, alone and in combination, on a daily energy budget. A uniform age effect evident in model outputs is reduced foraging efficiency. The components of this net effect are exacerbated for sub optimal behavioral-response settings or environmental conditions. The model predicts that with advancing age, efficiency declines increase for aging scenarios in the following order: simulated 'young' adults; 'old' seals with increased buoyancy; 'old' seals with reduced aerobic dive limit; 'old' seals having reduced muscle contractile efficiency; and, 'old' seals with all three conditions. The model indicates narrowed behavioral options to maintain positive energy balance in older animals, suggesting that behavioral plasticity may not allow older animals to compensate for age-related performance constraints. PMID- 20363232 TI - N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells. AB - Curcumin is a natural compound that has been extensively observed due to its potential as an anticancer drug. Curcumin restrains cancer cell progression via telomerase activity suppression. However, the exact mechanism is still unknown. In this study, we demonstrate that the effects of curcumin on cell viability and telomerase activity can be blunted by reactive oxygen species (ROS) inhibitor N acetyl cysteine (NAC). The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RT-PCR, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin. Sp1 is one of the important transcription factors in hTERT expression. Our data showed that curcumin decreases the expression of Sp1 through proteasome pathway. In addition, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin. Further, reporter assay and DNA affinity precipitation assay confirmed the influence of curcumin on Sp1 in hTERT regulation. This is the first study to demonstrate that curcumin induces ROS production resulting in Sp1 binding activity inhibition and hTERT downregulation. PMID- 20363233 TI - Sinapic acid attenuates kainic acid-induced hippocampal neuronal damage in mice. AB - Excitotoxin induces neurodegeneration via glutamatergic activation or oxidative stress, which means that the blockade of glutamate receptors and the scavenging of free radicals are potential therapeutic targets in neurodegenerative diseases. Sinapic acid (SA) has a GABA(A) receptor agonistic property and free radical scavenging activity. We investigated the neuroprotective effects of SA on kainic acid (KA)-induced hippocampal brain damage in mice. SA (10 mg/kg) by oral administration has an anticonvulsant effect on KA-induced seizure-like behavior. Moreover, SA (10 mg/kg) significantly attenuated KA-induced neuronal cell death in the CA1 and CA3 hippocampal regions when administered as late as 6 h after KA. In addition, flumazenil, a GABA(A) antagonist, blocked the effect of SA administered immediately after KA but not the effect of SA administered 6 h after KA. This late protective effect of SA was accompanied by reduced levels of reactive gliosis, inducible nitric oxide synthase expression, and nitrotyrosine formation in the hippocampus. In the passive avoidance task, KA-induced memory impairments were ameliorated by SA. These results suggest that the potential therapeutic effect of SA is due to its attenuation of KA-induced neuronal damage in the brain via its anti-convulsive activity through GABA(A) receptor activation and radical scavenging activity. PMID- 20363235 TI - The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. AB - Although it is long known that the tricyclic antidepressants amitriptyline, nortriptyline and imipramine inhibit the noradrenaline transporter and alpha(1) adrenoceptors with similar affinities, which may lead to self-cancelling actions, the selectivity of these drugs for alpha(1)-adrenoceptor subtypes is unknown. The present study investigates the selectivity of amitriptyline, nortriptyline and imipramine for human recombinant and rat native alpha(1)-adrenoceptor subtypes. The selectivity of amitriptyline, nortriptyline and imipramine was investigated in HEK-293 cells expressing each of the human alpha(1)-subtypes and in rat native receptors from the vas deferens (alpha(1A)), spleen (alpha(1B)) and aorta (alpha(1D)) through [(3)H]prazosin binding, and noradrenaline-induced intracellular Ca(2+) increases and contraction assays. Amitriptyline, nortriptyline and imipramine showed considerably higher affinities for alpha(1A)- (approximately 25- to 80-fold) and alpha(1D)-adrenoceptors (approximately 10- to 25-fold) than for alpha(1B)-adrenoceptors in both contraction and [(3)H]prazosin binding assays with rat native and human receptors, respectively. In addition, amitriptyline, nortriptyline and imipramine were substantially more potent in the inhibition of noradrenaline-induced intracellular Ca(2+) increases in HEK-293 cells expressing alpha(1A)- or a truncated version of alpha(1D)-adrenoceptors which traffics more efficiently towards the cell membrane than in cells expressing alpha(1B)-adrenoceptors. Amitriptyline, nortriptyline and imipramine are much weaker antagonists of rat and human alpha(1B)-adrenoceptors than of alpha(1A)- and alpha(1D)-adrenoceptors. The differential affinities for these receptors indicate that the alpha(1)-adrenoceptor subtype which activation is most increased by the augmented noradrenaline availability resultant from the blockade of neuronal reuptake is the alpha(1B)-adrenoceptor. This may be important for the behavioural effects of these drugs. PMID- 20363234 TI - Mechanisms of inhibition of CaV3.1 T-type calcium current by aliphatic alcohols. AB - Many aliphatic alcohols modulate activity of various ion channels involved in sensory processing and also exhibit anesthetic capacity in vivo. Although the interaction of one such compound, 1-octanol (octanol) with different T-type calcium channels (T-channels) has been described, the mechanisms of current modulation and its functional significance are not well studied. Using patch clamp technique, we investigated the mechanisms of inhibition of T-currents by a series of aliphatic alcohols in recombinant human Ca(V)3.1 (alpha1G) T-channel isoform expressed in human embryonic kidney (HEK) 293 cells and thalamocortical (TC) relay neurons in brain slices of young rats. Octanol, 1-heptanol (heptanol) and 1-hexanol (hexanol) inhibited the recombinant Ca(V)3.1 currents in concentration-dependent manner yielding IC(50) values of 362 microM, 1063 microM and 3167 microM, respectively. Octanol similarly inhibited native thalamic Ca(V)3.1 T-currents with an IC(50) of 287 microM and diminished burst firing without significant effect on passive membrane properties of these neurons. Inhibitory effect of octanol on T-currents in both native and recombinant cells was accompanied with accelerated macroscopic inactivation kinetics and hyperpolarizing shift in the steady-state inactivation curve. Additionally, octanol induced a depolarizing shift in steady-state activation curves of T current in TC neurons. Surprisingly, the recovery from fast inactivation at hyperpolarized membrane potentials was accelerated by octanol up 3-fold in native but not recombinant channels. Given the importance of thalamocortical pathways in providing sleep, arousal, and anesthetic states, modulation of thalamic T currents may at least contribute to the pharmacological effects of aliphatic alcohols. PMID- 20363236 TI - Identification of attention and cognitive control networks in a parametric auditory fMRI study. AB - In the competition for limited processing resources, top-down attention and cognitive control processes are needed to separate relevant from irrelevant sensory information and to interact with the environment in a meaningful way. The demands for the recruitment of top-down control processes depend on the relative salience of the competing stimuli. In the present event-related functional magnetic resonance imaging (fMRI) study we investigated the dynamics of neuronal networks during varying degrees of top-down control demands. We tested 20 participants with a dichotic auditory discrimination task in which the relative perceptual salience of two simultaneously presented syllables was parametrically varied by manipulating the inter-aural intensity differences (IIDs) and instructing the subjects to selectively attend to either the louder or weaker of the two stimuli. A significant interaction of IID manipulation and attentional instruction was detected bilaterally in the inferior parietal lobe and pre supplementary motor area, and in the precentral gyrus, anterior cingulate cortex, and inferior frontal gyrus of the right hemisphere. The post hoc analysis of the interaction pattern allowed for an assignment of these regions to either of two sets of regions which can be interpreted to constitute two different brain networks: a fronto-parietal attention control network, involved in the integration of saliency-based and instruction-based processing preferences, and a medial-lateral frontal cognitive control network, involved in the processing of the conflicts arising in the attempt to follow the attentional instruction in face of the varying inter-aural stimulus salience. PMID- 20363237 TI - Ecdysteroids elicit a rapid Ca2+ flux leading to Akt activation and increased protein synthesis in skeletal muscle cells. AB - Phytoecdysteroids, structurally similar to insect molting hormones, produce a range of effects in mammals, including increasing growth and physical performance. In skeletal muscle cells, phytoecdysteroids increase protein synthesis. In this study we show that in a mouse skeletal muscle cell line, C(2)C(12), 20-hydroxyecdysone (20HE), a common phytoecdysteroid in both insects and plants, elicited a rapid elevation in intracellular calcium, followed by sustained Akt activation and increased protein synthesis. The effect was inhibited by a G-protein coupled receptor (GPCR) inhibitor, a phospholipase C (PLC) inhibitor, and a phosphoinositide kinase-3 (PI3K) inhibitor. PMID- 20363238 TI - Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats. AB - We evaluated the interplay among estrogen, leptin and thyroid function in the regulation of body mass in female rats. Adult female rats were divided into four groups: control (C, sham-operated), ovariectomized (OVX), ovariectomized treated with estradiol benzoate (Eb) 0.7 or 14microg/100gbw per day, during 21 days. OVX led to an increase in body mass, food intake and food efficiency (change in body mass as function of the amount of food ingested) which were normalized by the lower Eb dose, and decreased significantly when the higher dose was given. Serum leptin levels were increased more than two-fold in all ovariectomized groups. Serum T4 levels of the Eb treated OVX were significantly lower than in the controls. Serum T3 and TSH were unaffected by OVX or by Eb treatment. Uterine type 2 iodothyronine deiodinase (D2) activity changed in parallel with serum estradiol: decreased after OVX, returned to control levels after the lower E2 treatment, and increased significantly after the high Eb dosage. The hypothalamic D2 activity was reduced around 30% in all castrated groups, treated or not with estrogen, whereas in the brown adipose tissue the enzyme was not changed. Interestingly, although estrogen-treated OVX rats had lower body weight, serum leptin was high, suggesting that estrogen increases leptin secretion. Our results show that estradiol is necessary for the hypothalamic action of leptin, since the increase in leptin levels observed in all ovariectomized rats was associated with a decrease in food intake and food efficiency only in the rats treated with estrogen. PMID- 20363239 TI - Dominance and the maintenance of polymorphism in multiallelic migration-selection models with two demes. AB - The maintenance of genetic variation in a spatially heterogeneous environment has been one of the main research themes in theoretical population genetics. Despite considerable progress in understanding the consequences of spatially structured environments on genetic variation, many problems remain unsolved. One of them concerns the relationship between the number of demes, the degree of dominance, and the maximum number of alleles that can be maintained by selection in a subdivided population. In this work, we study the potential of maintaining genetic variation in a two-deme model with deme-independent degree of intermediate dominance, which includes absence of G x E interaction as a special case. We present a thorough numerical analysis of a two-deme three-allele model, which allows us to identify dominance and selection patterns that harbor the potential for stable triallelic equilibria. The information gained by this approach is then used to construct an example in which existence and asymptotic stability of a fully polymorphic equilibrium can be proved analytically. Noteworthy, in this example the parameter range in which three alleles can coexist is maximized for intermediate migration rates. Our results can be interpreted in a specialist-generalist context and (among others) show when two specialists can coexist with a generalist in two demes if the degree of dominance is deme independent and intermediate. The dominance relation between the generalist allele and the specialist alleles play a decisive role. We also discuss linear selection on a quantitative trait and show that G x E interaction is not necessary for the maintenance of more than two alleles in two demes. PMID- 20363240 TI - Contextual effects on perceived three-dimensional shape. AB - Binocular disparity is a powerful cue for the perception of depth. The accuracy with which observers can judge depth from disparity can, however, be very poor. This has been attributed to difficulties associated with the scaling of disparity to take account of distance (Johnston, 1991). We test potential strategies that could be used to improve this scaling. Using the depth-to-width ratio task introduced by Bradshaw, Parton, and Eagle (1998), observers adjusted a depth interval to match the vertical distance between two points. The first experiment examined the effect of placing additional visual stimuli between the observer and the target. Despite the potential of these stimuli to provide reliable distance information, the accuracy of depth settings did not change. The second experiment demonstrated that the degree of binocular correlation present in natural images provides useful distance information, and investigated whether this is used by observers in scaling disparity. To do this, we measured whether varying the magnitude of relative disparity presented in the surround of the target affected depth settings. No such effect was observed. We conclude that the effect of information presented in the surrounding context on settings of depth is limited to those situations in which it provides direct information about the distance to the target. PMID- 20363241 TI - Detection vs. grouping thresholds for elements differing in spacing, size and luminance. An alternative approach towards the psychophysics of Gestalten. AB - Three experiments were performed to compare thresholds for the detection of non uniformity in spacing, size and luminance with thresholds for grouping. In the first experiment a row of 12 black equi-spaced dots was used and the spacing after the 3rd, 6th, and 9th dot increased in random steps to determine the threshold at which the observer detected an irregularity in the size of the gaps. Thereafter, spacing in the same locations was increased further to find the threshold at which the observer perceived four groups of three dots each (triplets). In the second experiment, empty circles were used instead of dots and the diameter of the circles in the first and second triplet increased until the difference in size gave rise either to a detection or grouping response. In the third experiment, the dots in the second and fourth triplet were increased in luminance. The aim again was to compare the difference in brightness required for detection or grouping, respectively. Results demonstrate that the threshold for perceiving stimuli as irregularly spaced or dissimilar in size or brightness is much smaller than the threshold for grouping. In order to perceive stimuli as grouped, stimulus differences had to be 5.2 times (for dot spacing), 7.4 times (for size) and 6.6 times (for luminance) larger than for detection. Two control experiments demonstrated that the difference between the two kinds of thresholds persisted even when only two gaps were used instead of three and when gap position was randomized. PMID- 20363243 TI - Age- and tissue-specific changes in mitochondrial and nuclear DNA base excision repair activity in mice: Susceptibility of skeletal muscles to oxidative injury. AB - In this study, we investigated age- and tissue-dependent changes in the DNA base excision repair (BER) of oxidative lesions in mitochondrial and nuclear extracts by measuring single-nucleotide (SN)- and long-patch (LP)-BER activities in five tissues isolated from 4-, 10- and 20-month-old mice. Age-dependent SN-BER and LP BER activity was increased in the mitochondria of liver, kidney and heart, but generally decreased in skeletal muscles. In contrast, no significant changes in repair activity were observed in nuclear extracts of the same tissues, except for quadriceps, where the SN-BER activity was higher in the old animals. Moreover, the BER activities in both the nucleus and the mitochondria were significantly lower in skeletal muscles compared to liver or kidney of the same mice. The protein level of three antioxidant enzymes, Mn and Cu/Zn superoxide dismutases (SOD) and catalase, was also significantly lower in skeletal muscle compared to liver or kidney. In addition, we found higher levels of protein carbonylation in the mitochondria of skeletal muscle relative to other tissues. Thus, it appears likely that mouse skeletal muscle is highly susceptible to oxidative stress due to deficiency in both repair of oxidative DNA damage and antioxidant enzymes, contributing to age-dependent muscle loss. PMID- 20363242 TI - Gene profiling in experimental models of eye growth: clues to myopia pathogenesis. AB - To understand the complex regulatory pathways that underlie the development of refractive errors, expression profiling has evaluated gene expression in ocular tissues of well-characterized experimental models that alter postnatal eye growth and induce refractive errors. Derived from a variety of platforms (e.g. differential display, spotted microarrays or Affymetrix GeneChips), gene expression patterns are now being identified in species that include chicken, mouse and primate. Reconciling available results is hindered by varied experimental designs and analytical/statistical features. Continued application of these methods offers promise to provide the much-needed mechanistic framework to develop therapies to normalize refractive development in children. PMID- 20363245 TI - Behavioural effects and regulation of PKCalpha and MAPK by huprine X in middle aged mice. AB - The behavioural effects of huprine X, a new anticholinesterasic inhibitor, as well as its effects on the regulation of protein kinase C (PKC), mitogen activated protein kinase (MAPK) and alpha-secretase (ADAM10 and TACE/ADAM17) related to amyloid precursor protein (APP) processing remain to be established. In the present work, 12 month old 126/SvxC57b/6 male mice which received chronic i.p. treatment with either saline, huprine X (0.04 micromol kg(-1) or huprine X (0.12 micromol kg(-1), were submitted to a battery of behavioural tests and thereafter the brains were dissected to study the neurochemical effects induced by huprine X. The results show that, in a dose dependent manner, huprine X facilitates learning and memory in the Morris water maze and improves some indicators of emotionality without inducing adverse effects, affecting motor activity nor anxiety-like behaviours, as measured in the open-field and corner tests. Moreover activation of downstream PKC/MAPK signaling pathways may underly these behavioural effects as well as the stimulation of the non-amyloidogenic processing of APP. Results obtained herein using a sample of aged animals strongly suggest that huprine X constitutes a promising therapeutic agent for the treatment of cholinergic dysfunction underlying aging and/or dementias. PMID- 20363246 TI - The mania-like exploratory profile in genetic dopamine transporter mouse models is diminished in a familiar environment and reinstated by subthreshold psychostimulant administration. AB - Bipolar Disorder (BD) is a neuropsychiatric disorder characterized by symptoms ranging from a hyperactive manic state to depression, with periods of relative stability, known as euthymia, in between. Although prognosis for BD sufferers remains poor, treatment development has been restricted due to a paucity of validated animal models. Moreover, most models focus on the manic state of BD with little done to characterize the longitudinal behavior of these models. We recently presented two dopamine transporter (DAT) mouse models of BD mania: genetic (DAT knockdown; KD, mice) and pharmacological (the selective DAT inhibitor GBR 12909). These models exhibit an exploratory profile consistent with the quantified exploratory profile of manic BD patients observed in the cross species translational test, the Behavioral Pattern Monitor (BPM). To further explore the suitability of these models, we examined the effects of reduced DAT function on the behavior of mice tested after familiarization to the BPM environment. Testing with 16mg/kg GBR 12909 in familiarized mice resulted in a consistent mania-like profile. In contrast, the mania-like profile of DAT KD mice disappears in a familiar environment, with partial reinstatement elicited by the introduction of novelty. In addition, we found that a subthreshold dose of GBR 12909 (9mg/kg) reinstated the mania-like profile in DAT KD mice without affecting wildtype behavior. Thus, the mania-like exploratory profile of DAT KD mice is reduced in a familiar environment, partially reinstated with novelty, but is fully restored when administered a stimulant that is ineffective in wildtype mice. These mice may provide a model of BD from mania to euthymia and back again with stimulant treatment. Acute blockade of the DAT by GBR 12909 however, may provide a consistent model for BD mania. PMID- 20363247 TI - Effects of lacquer polysaccharides, glycoproteins and isoenzymes on the activity of free and immobilised laccase from Rhus vernicifera. AB - The purified polysaccharides, glycoproteins, and isoenzymes of Rhus laccase, and crude enzymes, from Chinese lacquer (Rhus vernicifera sap) were used to determine their influence on the enzymic activity of Rhus laccase on several substrates (4 phenylenediamine, isoeugenol and coniferyl alcohol). No product identity changes were observed when these components were added singularly or in combination to the enzymic reactions (only relative product yields varied significantly), however, the polysaccharides (GP1 and GP2) and glycoprotein (stellacyanin, St) exhibited negative effects, and the two isoenzymes (L1 and L2) exhibited positive synergistic effects, on the activity of Rhus laccase. With respect to the activity of the crude enzymes, the negative effects of GP1, GP2 and St were greater than the positive effects of L1 and L2, compared with free Rhus laccase on its own (using 4-phenylenediamine as substrate), the estimated inhibitory effect (of GP1, GP2 and St) being by at least a factor of 50 (even with the positive effect of L1 and L2). This contributes to understanding of lacquer storage stability and drying rates. Immobilisation of crude enzymes using a variety of techniques (using natural and modified polysaccharides, and an inorganic support) where evaluated using isoeugenol as substrate. Agar embedding and zirconium chloride chelation methods resulted in the highest substrate conversion levels. The yields and products of isoeugenol catalysis using Vietnamese crude enzymes/purified Rhus laccase and commercial Denilite laccase were also compared and contrasted with their Chinese lacquer sap equivalents. PMID- 20363244 TI - Mitochondrial uncoupling and lifespan. AB - The quest to understand why we age has given rise to numerous lines of investigation that have gradually converged to include metabolic control by mitochondrial activity as a major player. That is, the ideal balance between nutrient uptake, its transduction into usable energy, and the mitigation of damaging byproducts can be regulated by mitochondrial respiration and output (ATP, reactive oxygen species (ROS), and heat). Mitochondrial inefficiency through proton leak, which uncouples substrate oxidation from ADP phosphorylation, can comprise as much as 30% of the basal metabolic rate. This uncoupling is hypothesized to protect cells from conditions that favor ROS production. Uncoupling can also occur through pharmacological induction of proton leak and activity of the uncoupling proteins. Mitochondrial uncoupling is implicated in lifespan extension through its effects on metabolic rate and ROS production. However, evidence to date does not suggest a consistent role for uncoupling in lifespan. The purpose of this review is to discuss recent work examining how mitochondrial uncoupling impacts lifespan. PMID- 20363248 TI - The primitive immune system of amphioxus provides insights into the ancestral structure of the vertebrate immune system. AB - Amphioxus is considered to be the basal chordate. However, the structural and anatomical features of the amphioxus immune system are still elusive. Here we report a profile of structural studies of the amphioxus gill and gut, the first line of defending against microbes, through optical and electron microscopy. The amphioxus gut and gill are characterized by the following morphological criteria compared with vertebrates: primary and secondary lymphoid-like tissue clustered in the gill, a thicker basement membrane with a large villus channel and lack of muscular layer in the gut, along with blood vessels that fill with phagocytes following microbial challenge. The phenomena of tissue repair after microbial invasion was observed, though no phagocytes were observed in the region of tissue necrosis. The epithelium cells of amphioxus gut showed active phagocytosis after the microbial challenge. A small number of free and fixed macrophage-like cells were also found in the amphioxus gut. The current results described the structure of the immune system and cellular defense against infection in a protochordate, which may help us in understanding the structural origin of the vertebrate immune system. PMID- 20363249 TI - A Dorsal homolog (FcDorsal) in the Chinese shrimp Fenneropenaeus chinensis is responsive to both bacteria and WSSV challenge. AB - Rel/NFkappaB is a family of transcription factors. In the present study, a Rel/NFkappaB family member, Dorsal homolog (FcDorsal) was cloned from the Chinese shrimp Fenneropenaeus chinensis. The full length cDNA of FcDorsal consists of 1627bp, revealed a 1071bp open reading frame encoding 357 aa. The predicted molecular weight (MW) of the deduced amino acid sequence of FcDorsal was 39.78kDa, and its theoretical pI was 8.85. Amino acid sequence analysis showed that FcDorsal contains a Rel homolog domain (RHD) and an IPT/TIG (Ig-like, plexins and transcriptions factors) domain. The signature sequence of dorsal protein existed in the deduced amino acid sequence. Spatial expression profiles showed that FcDorsal had the highest expression level in the hemocytes and lymphoid organ (Oka). The expression profiles in the hemocytes and lymphoid organ were apparently modulated when shrimp were stimulated by bacteria or WSSV. Both Gram-positive (G(+)) bacteria (Micrococcus lysodeikticus) and Gram-negative (G( )) bacteria (Vibrio anguillarium) injection to shrimp caused the up-regulation of FcDorsal at the transcription level. DsRNA approach was used to study the function of FcDorsal and the data showed that FcDorsal was related to the transcription of Penaeidin 5 in shrimp. The present data provide clues that FcDorsal might play potential important roles in the innate immunity of shrimp. Through comparison of the expression profiles between FcDorsal and another identified Rel/NFkappaB member (FcRelish) in shrimp responsive to WSSV challenge, we speculate that FcDorsal and FcRelish might play different roles in shrimp immunity. PMID- 20363250 TI - Phylogenetic and expression analysis of lamprey toll-like receptors. AB - Toll-like receptors (TLRs) have been identified as pivotal sensors recognizing microbial pattern molecules in vertebrates. Whole genome analysis of the teleost Takifugu rubripes supports the existence of a fundamental family of TLR genes in fish. However, the role of the innate immune system in the context of raising acquired immunity in jawless fish remains unclear. In this study, we annotated 16 lamprey TLR genes predicted from the latest genome assembly of lamprey on the basis of homology, and identified their cDNAs from Japanese lamprey, Lethenteron japonicum. Phylogenetic analyses indicated that the repertoire of lamprey TLRs consisted of both fish (F)- and mammalian (M)-type TLRs, and it was also demonstrated that lamprey TLRs are constitutively expressed in various organs. Our results suggest that lampreys protect against microorganisms using the innate system consisting of a similar set of M- and F-type TLRs, despite possessing a unique acquired immune system. In addition, type I interferon (IFN), interferonregulatory factor (IRF)-3, and IRF7 were not identified in the lamprey genome although TLR adaptor and signal transduction genes were highly conserved upstream of (IRF)-3/7 and type I IFN in most vertebrates. This is the first report to describe the TLR repertoire and IFN system in one of the most primitive vertebrates, the lamprey. PMID- 20363251 TI - SpTie1/2 is expressed in coelomocytes, axial organ and embryos of the sea urchin Strongylocentrotus purpuratus, and is an orthologue of vertebrate Tie1 and Tie2. AB - A full length cDNA sequence expressed in coelomocytes shows significant sequence match to vertebrate Tie1 and Tie2/TEK. Vertebrate Tie2/TEK is the receptor for the angiopoietins and plays an important role in angiogenesis and hematopoiesis, whereas Tie1 regulates the activity of Tie2. The deduced sequence of the SpTie1/2 protein has a similar order and organization of domains to the homologous vertebrate proteins including a highly conserved receptor tyrosine kinase domain in the cytoplasmic tail. The N terminus of the ectodomain has one immunoglobulin (Ig)-Tie2_1 domain, followed by an Ig domain, four epidermal growth factor domains, a second Ig domain, and three fibronectin type III domains. The SpTie1/2 gene is expressed in coelomocytes and the axial organ, whereas other organs do not show significant expression. The timing of embryonic expression corresponds with the differentiation of blastocoelar cells, the embryonic and larval immune cells. Searches of the sea urchin genome show several gene models encoding putative ligands and signaling proteins that might interact with SpTie1/2. We speculate that SpTie1/2 may be involved in the proliferation of sea urchin immune cells in both adults and embryos. PMID- 20363252 TI - Do antibiotic-impregnated catheters prevent infection in CSF diversion procedures? Review of the literature. AB - SUMMARY: Cerebrospinal fluid shunting devices are foreign bodies internally or externally placed in a patient with the aim of improving the prognosis. Device related infection is the most serious complication. Its importance arises from the high frequency of occurrence and the consequences that it implies in terms of morbidity and mortality. As a result, the presence of these two factors increases significantly hospital costs. Among many primary prevention measures investigated, one of those that has gained in importance over the last years is the use of antibiotic-impregnated catheters. Although their experimental development dates back to the 1970s, experience in clinical practice has not been settled until the last decade. This is the reason why only 22 studies on the usefulness of AICs in CSF shunting procedures in clinical practice have been published in the literature since their commercialization. Although experience with antibiotic-impregnated shunts continues growing, practice with antibiotic impregnated external ventricular drains is much shorter. The present study reviews and analyses the different investigations performed in order to determine the efficacy of antibiotic-impregnated shunts and external ventricular drains with the aim of reducing device-related infectious complications. The results suggest that AICs reduce device-related infection as well as hospital costs. However, evidence is not enough to state categorical conclusions, and further large, prospective, randomized and double-blind studies must be performed in order to confirm these results and the efficacy of other antibiotic-impregnated devices. Further economic evaluation is required to confirm the benefit in terms of cost-effectiveness as well. PMID- 20363253 TI - The liver X receptor: control of cellular lipid homeostasis and beyond Implications for drug design. AB - Liver X receptor (LXR) alpha and beta are nuclear receptors that control cellular metabolism. LXRs modulate the expression of genes involved in cholesterol and lipid metabolism in response to changes in cellular cholesterol status. Because of their involvement in cholesterol homeostasis, LXRs have emerged as promising drug targets for anti-atherosclerotic therapies. In rodents, synthetic LXR agonists promote cellular cholesterol efflux, transport and excretion. As a result, the progression of atherosclerosis is halted. However, pharmacological LXR activation also induces hepatic steatosis and promotes the secretion of atherogenic triacylglycerol-rich VLDL particles by the liver, complicating the clinical application of LXR agonists. The more recently emerged roles of LXRs in fat tissue, pituitary and brain may have implications for treatment of obesity and Alzheimer disease. In addition to the improvements in atherosclerosis, LXR activation exerts beneficial effects on glucose control in mouse models of type 2 diabetes. Future therapeutic strategies aiming to exert beneficial effects on cholesterol and glucose homeostasis, while circumventing the undesired effects on hepatic lipid metabolism, should target specific LXR-mediated processes. Therefore, tissue and/or isotype-specific effects of LXR action need to be established. The consequences of combinatorial drug approaches and the identification of the co-regulatory networks involved in the LXR-mediated control of particular genes may contribute to development of novel LXR agonists. Finally, pathway analyses of LXR actions provide tools to evaluate and optimize the effectiveness of novel therapeutic strategies to prevent and/or treat metabolic diseases. PMID- 20363254 TI - Visualization and modelling of STLmax topographic brain activity maps. AB - This paper evaluates the descriptive power of brain topography based on a dynamical parameter, the Short-Term Maximum Lyapunov Exponent (STLmax), estimated from EEG, for finding out a relationship of STLmax spatial distribution with the onset zone and with the mechanisms leading to epileptic seizures. Our preliminary work showed that visual assessment of STLmax topography exhibited a link with the location of seizure onset zone. The objective of the present work is to model the spatial distribution of STLmax in order to automatically extract these features from the maps. One-hour preictal segments from four long-term continuous EEG recordings (two scalp and two intracranial) were processed and the corresponding STLmax profiles were estimated. The spatial STLmax maps were modelled by a combination of two Gaussians functions. The parameters of the fitted model allow automatic extraction of quantitative information about the spatial distribution of STLmax: the EEG signal recorded from the brain region where seizures originate exhibited low-STLmax levels, long before the seizure onset, in 3 out of 4 patients (1 out of 2 of scalp patients and 2 out of 2 in intracranial patients). Topographic maps extracted directly from the EEG power did not provide useful information about the location, therefore we conclude that the analysis so far carried out suggests the possibility of using a model of STLmax topography as a tool for monitoring the evolution of epileptic brain dynamics. In the future, a more elaborate approach will be investigated in order to improve the specificity of the method. PMID- 20363255 TI - Activation of RAW264.7 macrophages by oxidized galectin-1. AB - Galectin-1, a member of the beta-galactoside-binding lectin family, exists in both reduced and oxidized states. Oxidized galectin-1 (Gal-1/Ox), which lacks lectin activity, has been shown to promote axonal regeneration after injury by activating macrophages, which causes the release of factors that enhance Schwann cell migration and neurite outgrowth. However, the mechanism of macrophage activation by Gal-1/Ox remains unknown. In this study, we examined the effects of Gal-1/Ox on RAW264.7 macrophages and RT4-D6P2T Schwann cells. Gal-1/Ox stimulated migration of RT4-D6P2T Schwann cells directly and by activating RAW264.7 macrophages to release factors that promoted cell migration. Gal-1/Ox inhibited nitric oxide (NO) production induced by interferon-gamma by suppressing expression of inducible NO synthase in RAW264.7 macrophages and not by arginase activation and cell death. Furthermore, Gal-1/Ox-activated extracellular signal regulated protein kinase 1/2 (ERK1/2) in RAW264.7 macrophages, although the mitogen-activated protein kinase (MEK)/ERK1/2 pathway was not involved in release of factors that promoted Schwann cell migration. On the other hand, Gal-1/Ox induced RT4-D6P2T Schwann cell migration appeared to be mediated by the MEK/ERK1/2 pathway. These results suggest that Gal-1/Ox inhibits inflammatory responses in macrophages and promotes Schwann cell migration directly and by macrophage activation. PMID- 20363256 TI - Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells. AB - Rimexolone is a lipophilic glucocorticoid drug used for local application. Only few data are available describing its effects on immune cell functions. In this study we investigated the effects of rimexolone on the proliferation of human CD4+ T-cells using dexamethasone as standard reference. Isolated CD4+ T-cells were pre-incubated with rimexolone or dexamethasone at different concentrations for 10 min (10(-11)/10(-8)/10(-5)M) and stimulated with anti-CD3/anti-CD28 for 96 h. Proliferation was determined by flow cytometry. The percentage of dividing cells was significantly reduced by 10(-5)M rimexolone and dexamethasone; however, the average number of cell divisions was unchanged. In addition, production of IL 2 and other cytokines was reduced by both glucocorticoids at 10(-5)M. Interestingly, we observed a rimexolone-induced down-regulation of CD4 expression in unstimulated and non-dividing cells. The inhibitory effects on proliferation and CD4 expression could be blocked by the glucocorticoid-antagonist RU486 and were not due to glucocorticoid-induced apoptosis. Rimexolone and dexamethasone showed a similar potential to induce IkappaBalpha gene expression. We demonstrate rimexolone and dexamethasone to impair T-cell signalling pathways by rapid non genomic suppression of the phosphorylation of Akt, p38 and ERK. We conclude that rimexolone and dexamethasone inhibit T-cell proliferation as well as cytokine production of activated CD4+ T-cells in a similar manner. As these inhibitory effects predominantly occur at high concentrations, a relatively high occupation rate of cytosolic glucocorticoid receptors is needed, but receptor-mediated non genomic effects may also be involved. It is implied that these effects contribute to the well-known beneficial anti-inflammatory and immunomodulatory effects of glucocorticoid therapy. PMID- 20363257 TI - A small molecule inhibits HCV replication and alters NS4B's subcellular distribution. AB - Hepatitis C Virus (HCV) is a leading cause of liver disease and represents a significant public health challenge. Treatments for this disease are inadequate and improved antiviral therapies are necessary. Several such antivirals are in development, most of which target the well-characterized NS3 protease or the NS5B polymerase. In contrast, the nonstructural 4B (NS4B) protein, though essential for HCV RNA replication, has been the subject of few pharmacological studies. One of the functions ascribed to this protein is the ability to form intracellular membrane-associated foci (MAF), which are believed to be related to the sites of viral replication. Here, we report the identification of a small molecule that inhibits HCV replication and disrupts the organization of these MAF. Genetic analysis links the compound's mode of action to the NS4B gene product, and transient transfections of NS4B-GFP demonstrate that treatment with this compound can lead to the formation of novel elongated assemblies of NS4B. Furthermore, an in vitro dynamic light scattering assay provides evidence that the second amphipathic helix of NS4B may be the target of the drug. Our results demonstrate that this molecule represents a new potential class of HCV inhibitors and also provides us with a useful tool for studying the HCV life cycle. PMID- 20363258 TI - Altered emotionality leads to increased pain tolerance in amyloid beta (Abeta1 40) peptide-treated mice. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the decline in cognitive functions, but it is also related to emotional disturbances. Since pain experience results from a complex integration of sensory, cognitive and affective processes, it is not surprising that AD patients display a distinct pattern of pain responsivity. We evaluated whether mice treated with amyloid beta (Abeta) peptide-thought to be critical in the pathogenesis of AD-exhibit altered pain responses and its relation to altered emotionality. Mice received a single i.c.v. injection of vehicle (PBS) or Abeta fragment (1-40) (400pmol/mice) and after 30 days, they were evaluated in tests of pain (hotplate, footshock sensitivity), learning/memory (water-maze), emotionality (elevated plus-maze, forced swim) and locomotion (open-field). Abeta(1-40)-treated mice presented similar latencies to the control group in the hotplate test and similar nociceptive flinch threshold in the footshock-sensitivity test. However, they presented an increased jump threshold in footshock-sensitivity, suggesting increased pain tolerance. Altered emotionality was observed in the elevated plus maze (EPM) and forced-swim tests (FST), suggesting anxiogenic-like and depressive like states, respectively. A multifactorial principal component analysis (PCA) revealed that jump threshold of the footshock-sensitivity test falls within 'Emotionality' and 'Pain', showing moderate correlation with each one of the components of behavior. Acute treatment with the antidepressant desipramine (10mg/kg, i.p.) reduced the jump threshold (i.e. pain tolerance) and time of immobility in FST (i.e. depressive-like state). Flinch threshold (i.e. pain sensitivity), locomotion and anxiety were not altered with desipramine treatment. These results suggest that Abeta(1-40) peptide increases pain tolerance, but not pain sensitivity in mice, which seems to be linked to alterations in cognitive/emotional components of pain processing. PMID- 20363259 TI - Progesterone and maternal aggressive behavior in rats. AB - Females usually display low levels of aggressiveness; however, during lactation, the aggressive behavior against intruders to the nest area is an important component of the maternal behavioral repertoire. The present study aimed to analyze the influence of progesterone (P4) on the maternal aggressive behavior in rats. Lactating rat were ovariectomized on the first day after delivery and, on the 6th postpartum day, aggressive behaviors against a male intruder were recorded. Also in the 6th PPD, the effects of a P4 receptor antagonist (RU 486) as well as of finasteride - which inhibits the conversion of P4 to its metabolite allopregnanolone - on the aggressive behavior of non-ovariectomized lactating rats were analyzed. Finally, plasma concentration of prolactin was measured on the 8th PPD. This study shows, for the first time, that ovariectomy just after parturition reduces some aspects of the maternal behavior (frequency of licking) and the aggressive behavior and increased plasma prolactin. On the other hand, the administration of RU486 induced a marked increase in the aggressiveness of lactating females. No changes were detected after finasteride injection. Gonadal hormones after parturition seem necessary for the development of maternal aggressive behavior. Furthermore, our results suggest that the increase in P4 levels throughout the postpartum period could be one of the causes for the natural reduction of the aggressive behavior in lactating rats. PMID- 20363260 TI - Pragmatic and idiosyncratic acts in human everyday routines: the counterpart of compulsive rituals. AB - Our daily activities are comprised of motor routines, which are behavioral templates with specific goals, typically performed in an automatic fixed manner and without much conscious attention. Such routines can seem to resemble pathologic rituals that dominate the motor behavior of obsessive-compulsive disorder (OCD) and autistic patients. This resemblance raises the question of what differentiates and what is common in normal and pathologic motor behavior. Indeed, pathologic motor performance is often construed as an extended stereotyped version of normal everyday routines. In this study we applied ethological tools to analyze six motor routines performed by 60 adult human volunteers. We found that longer normal everyday routines included more repetitions, but not more types of acts, and that in each routine, most acts were performed either by all individuals (pragmatic acts) or by only one individual (idiosyncratic components). Thus, normal routines consist in a relatively rigid part that is shared by all individuals that perform the routine, and a flexible part that varies among individuals. The present results, however, do not answer the question of whether the flexible individual part changes or remains constant over routine repetition by the same person. Comparing normal routines with OCD rituals revealed that the latter comprise an exaggeration of the idiosyncratic component. Altogether, the present study supports the view that everyday normal routines and pathologic rituals are opposite processes, although they both comprise rigid motor behavioral sequences. PMID- 20363262 TI - Knockout of the gene encoding the kinetoplast-associated protein 3 (KAP3) in Trypanosoma cruzi: effect on kinetoplast organization, cell proliferation and differentiation. AB - Kinetoplast DNA (kDNA) of trypanosomatid protozoa consists of an unusual arrangement of two types of circular molecules catenated into a single network: (1) a few maxicircles that encode various mitochondrial enzyme subunits and rRNA in a cryptic pattern and (2) thousands of minicircles that encode guide RNAs (gRNAs). kDNA is associated with proteins, known as kinetoplast-associated proteins (KAPs), which condense the kDNA network. However, little is known about the KAPs of Trypanosoma cruzi, a parasite that displays different kDNA condensation patterns during its complex morphogenetic development. We cloned the T. cruzi gene encoding TcKAP3 (kinetoplast-associated protein 3). TcKAP3 is a single-copy gene that is transcribed into a 1.8-kb mRNA molecule and expressed in all stages of the parasite. Mouse antiserum raised against recombinant TcKPA3 recognized a 21.8kDa protein, which was found, by indirect immunofluorescence and immunoelectron microscopy, to be associated with the T. cruzi kinetoplast. Several features of TcKAP3, such as its small size, basic nature and similarity with KAP3 from the insect trypanosomatid Crithidia fasciculata, are consistent with a role in DNA charge neutralization and condensation. This suggests that this protein is involved in organizing the kDNA network. Gene deletion was used to investigate TcKAP3 function. Here we investigated the T. cruzi KAP3 null mutant, analyzing its fitness during proliferation, differentiation and infectivity. PMID- 20363261 TI - Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. AB - Memantine is a partial NMDA receptor antagonist that has been shown to improve learning and memory in several animal models, and is approved for the treatment of Alzheimer's disease (AD). Chronic treatments using memantine in animal models of Alzheimer's disease show disease-modifying effects and suggest a potential neuroprotective function. The present study assessed the effects of both short- and long-term memantine treatment in a mouse model of Down syndrome (DS), the Ts65Dn mouse. The Ts65Dn mouse contains a partial trisomy of murine chromosome 16, and exhibits hippocampal-dependent memory deficits, as well as progressive degeneration of basal forebrain cholinergic neurons (BCFNs). Ts65Dn mice were treated with memantine for a period of 6 months, beginning at 4 months of age. At the end of treatment the mice underwent memory testing using novel object recognition and water radial arm maze tasks, and then histologically analyzed for markers of neurodegeneration. Memantine treatment improved spatial and recognition memory performance in the Ts65Dn mice, though not to the level of normosomic littermate controls. Despite these memory improvements, histological analysis found no morphological signs of neuroprotection of basal forebrain cholinergic or locus coeruleus neurons in memantine-treated Ts65Dn mice. However, memantine treatment of Ts65Dn mice gave rise to elevated brain-derived neurotrophic factor expression in the hippocampus and frontal cortex, suggesting a mechanism of behavioral modification. Thus, our findings provide further evidence for memory facilitation of memantine, but suggest pharmacological rather than neuroprotective effects of memantine both after acute and chronic treatment in this mouse model. PMID- 20363263 TI - Processing of a phosphoglycerate kinase reporter mRNA in Trypanosoma brucei is not coupled to transcription by RNA polymerase II. AB - Capping of mRNAs is strictly coupled to RNA polymerase II transcription and there is evidence, mainly from metazoans, that other steps in pre-mRNA processing show a similar linkage. In trypanosomes, however, the mRNA cap is supplied by a trans spliced leader sequence. Thus pre-mRNAs transcribed by RNA Polymerase I are capped by trans splicing, and translation-competent transgenic mRNAs can be produced by RNA Polymerase I and T7 RNA polymerase so long as the primary transcript has a splice acceptor signal. We quantified the efficiency of processing of trypanosome pre-mRNAs produced from a plasmid integrated either at the tubulin locus, or in an rRNA spacer, and transcribed by RNA polymerase II, RNA polymerase I or T7 RNA polymerase. The processing efficiencies were similar for primary transcripts from the tubulin locus, produced by RNA polymerase II, and for RNA from an rRNA spacer, transcribed by RNA polymerase I. Primary transcripts produced by T7 RNA polymerase from the tubulin locus were processed almost as well. There was therefore no evidence for recruitment of the 3' splicing apparatus by the RNA polymerase. Abundant transcripts transcribed from the rRNA locus by T7 RNA polymerase were somewhat less efficiently processed. PMID- 20363264 TI - Genetic changes during laboratory propagation: copy number At the reticulocyte binding protein 1 locus of Plasmodium falciparum. AB - Comparative genomic hybridization studies have revealed elevated copy number (CN) at the reticulocyte-binding protein 1 gene (PfRh1) in fast growing lab-adapted parasites, while genetic manipulation demonstrates a causal link between cell invasion and PfRh1 CN. We therefore examined PfRh1 copy number variation (CNV) in 202 single clone parasite isolates from four countries to quantify the extent of CNV within natural populations. Surprisingly, we found that no natural parasite infections showed elevated CN. In contrast, 4/28 independent laboratory reference strains show elevated CN. One possibility is that amplification of PfRh1 (or neighboring loci) is selected during laboratory culture. In the case of FCR3 group of parasites, clone trees show that PfRh1 amplification arose in laboratory lines following establishment in culture. These data show that CNV at PfRh1 is rare or non-existent in natural populations, but can arise during laboratory propagation. We conclude that PfRh1 CNV is not an important determinant of gene expression, cell invasion or growth rate in natural parasite populations. PMID- 20363265 TI - Perspective: microfluidic applications in microbiology. AB - The application of microfluidics technology to microbiology research is an excellent platform for the analysis of microorganisms and their nucleic acids. This technology combines engineering, physics, chemistry, biology and computing to control the devices. In this perspective we discuss how microfluidics can be applied to microbiological research and used in diagnostic applications. We also summarize advantages and limitations of this technology, as well as highlight some recent microbiological applications. PMID- 20363266 TI - Fluorescent differential display analysis of Lactobacillus sakei strains under stress conditions. AB - Lactobacillus (Lb.) sakei is widely used as starter in the production process of Italian fermented sausages and its growth and survival are affected by various factors such as temperature, pH and salt concentration. We studied the behaviour of Lb. sakei strains under various growth conditions relative to acid, osmotic and heat stress treatments by a novel fluorescent differential display (FDD) technique. This study obtained the development and the optimization of a technique that allows the identification of genome expression changes, associated with differential microbial behaviour under different stress conditions with a better stress response definition and a better discrimination of starter cultures. DNA sequence information from the FDD products provided an important tool to assess and observe the response to a variety of environmental stimuli and the adaptation to bacterial stress. Our work provided an innovative FDD method, with a high level of reproducibility and quality for studying and probing the knowledge of the relation between differential genome expression and different stresses tolerance. PMID- 20363267 TI - A new hybrid protein for production of recombinant bacteriorhodopsin in Escherichia coli. AB - Unique properties of bacteriorhodopsin, namely, photochromism and high thermal stability, make this protein an attractive target for physico-chemical studies, as well as for various biotechnological applications. Using Mistic as a suitable carrier for insertion of recombinant membrane proteins into cytoplasmic membrane of Escherichia coli, we developed a system for overexpression of bacteriorhodopsin and worked out an efficient procedure for its purification and renaturation with the final yield of 120 mg/l of refolded protein, which is the highest value reported to date for bacteriorhodopsin produced in E. coli. Functional activity of recombinant bacteriorhodopsin was confirmed by spectroscopic and electrochemical assays. PMID- 20363268 TI - Metabolomics-driven approach for the improvement of Chinese hamster ovary cell growth: overexpression of malate dehydrogenase II. AB - We have established a liquid chromatography-mass spectrometry based metabolomics platform to identify extracellular metabolites in the medium of recombinant Chinese hamster ovary (CHO) fed-batch reactor cultures. Amongst the extracellular metabolites identified, malate accumulation was the most significant. The contributing factors to malate efflux were found to be the supply of aspartate from the medium, and an enzymatic bottleneck at malate dehydrogenase II (MDH II) in the tricarboxylic acid cycle. Subsequent metabolic engineering to overexpress MDH II in CHO resulted in increases in intracellular ATP and NADH, and up to 1.9 fold improvement in integral viable cell number. PMID- 20363269 TI - Isolation and analysis of two naturally-occurring multi-recombination Newcastle disease viruses in China. AB - Two Newcastle disease viruses (NDV), designated QG/Hebei/07 and XD/Shandong/08, were isolated from infected chicken flocks in China in 2007 and 2008, respectively. The results of phylogenetic and recombination analyses on complete NDV genome sequences (excluding terminal segments) show that the QG/Hebei/07 isolate had evidence of recombination in the M and F genes, and recombination in the XD/Shandong/08 isolate in the F, L genes and the non-coding region between the HN and L genes. These two naturally-occurring recombinants we found to be descended from at least three putative parents from vaccine and circulating virus lineages. Moreover, we found that evidence that homologous recombination also occurred between NDV viruses of chicken and swine lineages, while the major putative parent is likely to have been derived from the chicken avirulent vaccine lineage. This study suggests that homologous recombination can occur in all coding and non-coding regions of the NDV genome and a live vaccine strain is capable of recombination with circulating viruses resulting in significant genetic change. The potential role of swine-origin viruses in the evolution of virulent NDV warrants further investigation. PMID- 20363270 TI - C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats. AB - The aim was to study the effects of C-type natriuretic peptide (CNP) on mean arterial pressure (MAP) and the cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHR), and to investigate the signaling pathways involved in this interaction. SHR and WKY rats were infused with saline or CNP. MAP and nitrites and nitrates excretion (NO(x)) were determined. Catalytic NO synthase (NOS) activity and endothelial (eNOS), neuronal (nNOS) and inducible NOS (iNOS) were measured in the heart and aorta artery. NOS activity induced by CNP was determined in presence of: iNOS or nNOS inhibitors, NPR-A/B natriuretic peptide receptors blocker and Gi protein and calmodulin inhibitors. CNP diminished MAP and increased NO(x) in both groups. Cardiovascular NOS activity was higher in SHR than in WKY. CNP increased NOS activity, but this activation was lower in SHR. CNP had no effect on NOS isoforms expression. iNOS and nNOS inhibitors did not modify CNP-induced NOS activity. NPR-A/B blockade induced no changes in NOS stimulation via CNP in both tissues. Cardiovascular NOS response to CNP was reduced by Gi protein and calmodulin inhibitors in both groups. CNP interacts with NPR-C receptors, activating Ca-calmodulin eNOS via Gi protein. NOS response to CNP is impaired in the heart and aorta of SHR. Alterations in the interaction between CNP and NO would be involved in the maintenance of high blood pressure in this model of hypertension. PMID- 20363271 TI - Cell selectivity and anti-inflammatory activity of a Leu/Lys-rich alpha-helical model antimicrobial peptide and its diastereomeric peptides. AB - To investigate the effect of the number and distribution of d-amino acids introduced into non-cell-selective alpha-helical antimicrobial peptides on the cell selectivity, protease stability and anti-inflammatory activity, we synthesized an 18-meric Leu/Lys-rich alpha-helical model peptide (K(9)L(8)W) and d-amino acid-containing diastereomeric peptides. Increasing in cell selectivity of the peptides was increased in parallel with increasing in the number of d amino acids introduced. Despite having the same number of d-amino acids, D(9) K(9)L(8)W-1 had better cell selectivity than D(9)-K(9)L(8)W-2, indicating that a dispersed distribution of d-amino acids in diastereomeric peptides is more effective for cell selectivity than their segregated distribution. D(3)-K(9)L(8)W 2, D(6)-K(9)L(8)W, D(9)-K(9)L(8)W-1 and D(9)-K(9)L(8)W-2 showed complete resistance to tryptic digestion. Furthermore, K(9)L(8)W and all of its diastereomeric peptides significantly inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) mRNA expression and tumor necrosis factor alpha (TNF-alpha) release in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells at a lower concentration than bactericidal concentration. The order of anti-inflammatory activity for the peptides was K(9)L(8)W approximately D(3)-K(9)L(8)W-1 approximately D(3)-K(9)L(8)W-2 approximately D(6)-K(9)L(8)W approximately D(9)-K(9)L(8)W-2>D(4)-K(9)L(8)W>D(9)-K(9)L(8)W-1. Increasing in hydrophobicity or alpha-helicity of the peptides was more closely correlated with increasing in hemolytic activity and anti-inflammatory activity than antimicrobial and LPS-disaggregation activities. Collectively, we successfully developed several d-amino acid-containing antimicrobial peptides (D(4)-K(9)L(8)W, D(6)-K(9)L(8)W and D(9)-K(9)L(8)W-1) with good cell selectivity, protease stability and potent anti-inflammatory activity. These antimicrobial peptides could serve as templates for the development of peptide antibiotics for the treatment of sepsis, as well as microbial infection. PMID- 20363273 TI - Association between matrix metalloproteinase 9 promoter polymorphisms and Behcet's disease. AB - Matrix metalloproteinase (MMP)-9 expression is reported to be upregulated in several primary vasculitides. The -1562C>T and -91 [CA](n) repeat polymorphisms can affect MMP-9 promoter activity. We investigated the distributions of these functional polymorphisms in 122 patients with Behcet's disease (BD) and in 122 gender- and age-matched healthy controls. Plasma levels of MMP-9 were analyzed. The frequency of "L" alleles with [CA](n) <21 was significantly lower in all BD patients (vs controls, odds ratio (OR) = 0.371 [95% confidence interval 0.152 0.905]) and male patients (vs male controls, OR = 0.117 [0.019-0.737]). Furthermore, the frequency of "H/H" homozygote with [CA](n) > or = 21 was significantly higher in BD patients than controls (OR = 2.677 [1.065-6.729]). Moreover, the frequency of CL haplotype with lower promoter activity was significantly lower in BD patients (vs controls, OR = 0.374 [0.149-0.939]) and in BD patients with visceral involvement (OR = 0.202 [0.044-0.916]). Although plasma MMP-9 levels were not different between controls and BD patients, concentrations of this substance were significantly higher in male patients (vs male controls, p = 0.044) or patients with visceral involvements (vs patients without visceral involvement, p = 0.027). These results suggest that MMP-9 is a novel susceptibility gene and its promoter polymorphisms can affect the development of visceral involvement in BD. PMID- 20363275 TI - In silico approaches to predicting cancer potency for risk assessment of genotoxic impurities in drug substances. AB - The current risk assessment approach for addressing the safety of very small concentrations of genotoxic impurities (GTIs) in drug substances is the threshold of toxicological concern (TTC). The TTC is based on several conservative assumptions because of the uncertainty associated with deriving an excess cancer risk when no carcinogenicity data are available for the impurity. It is a default approach derived from a distribution of carcinogens and does not take into account the properties of a specific chemical. The purpose of the study was to use in silico tools to predict the cancer potency (TD(50)) of a compound based on its structure. Structure activity relationship (SAR) models (classification/regression) were developed from the carcinogenicity potency database using MultiCASE and VISDOM. The MultiCASE classification models allowed the prediction of carcinogenic potency class, while the VISDOM regression models predicted a numerical TD(50). A step-wise approach is proposed to calculate predicted numerical TD(50) values for compounds categorized as not potent. This approach for non-potent compounds can be used to establish safe levels greater than the TTC for GTIs in a drug substance. PMID- 20363277 TI - The impact of early-onset cannabis use on functional brain correlates of working memory. AB - Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. PMID- 20363276 TI - The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients. AB - BACKGROUND: Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D(2) blockade, in psychiatric patients treated with perospirone. METHODS: The subjects consisted of 21 adults treated with perospirone (4-60 mg/day). The plasma perospirone and ID15036 levels were measured in 21 patients and serum prolactin levels were investigated in 10 male patients with schizophrenia. RESULTS: The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p=0.032). The 10 male patients showed a positive correlation between the plasma perospirone levels and plasma prolactin levels (r=0.688, p=0.028) and between the plasma ID15036 levels and prolactin levels (r=0.775, p=0.009). CONCLUSION: The plasma levels of ID15036 may have a greater impact on the dopamine D(2) blockade than perospirone in patients treated with perospirone. PMID- 20363278 TI - Individual fumonisin exposure and sphingoid base levels in rural populations consuming maize in South Africa. AB - Low and high oesophageal cancer incidence areas of the former Transkei region of South Africa have been associated with corresponding low and high levels of fumonisin contaminated home-grown maize. This is the first study in South Africa assessing fumonisin B (FB) mycotoxin exposure by quantifying individual maize consumption with weighed food records and FB levels from maize in each participant's household and concurrently evaluating sphinganine (Sa), sphingosine (So) and Sa/So ratios in plasma and urine of these participants as possible biomarkers of FB exposure. The high consumption of maize in Bizana (n=36) and Centane (n=30) of 0.41+/-0.21 and 0.39+/-0.19 kg/day, respectively, confirms the reliance on maize as the dietary staple. Mean total FB (FB(1)+FB(2)+FB(3)) levels in home-grown maize were 0.495+0.880 and 0.665+0.660 mg/kg in Bizana and Centane, respectively. Mean fumonisin exposure based on individual consumption was 3.9+/ 7.3 and 4.1+/-7.6 microg/kg body weight/day, respectively, for Bizana and Centane. The mean combined sphinganine/sphingosine ratios in Bizana and Centane were similar and ranged from 0.10-0.55 in plasma (n=41) and urine (n=62). There was no association between sphingoid base levels and/or Sa/So ratios in the plasma and urine and individual fumonisin exposure, negating the sphingoid bases as potential biomarkers of fumonisin exposure in humans. PMID- 20363279 TI - Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan). AB - An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 microg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines. PMID- 20363280 TI - Ecklonia cava extracts inhibit lipopolysaccharide induced inflammatory responses in human endothelial cells. AB - Ecklonia cava (EC) is a brown alga that evidences radical scavenging, bactericidal, tyrosinase inhibitory and protease inhibitory activities. However, the antiinflammatory effects in human endothelial cells and its molecular mechanism remain poorly understood. In this study, we attempted to determine whether pretreatment with EC extracts induce a significant inhibition of antiinflammatory activities in lipopolysaccharide (LPS) induced human endothelial cells. We found that each EC extract inhibits LPS induced barrier permeability, expression of cell adhesion molecules, monocytes adhesion, and transendothelial migration to human endothelial cells. Further studies revealed that EC extracts suppress the production of tumor necrosis factor-alpha (TNF-alpha) and activation of nuclear factor-kappa B (NF-kappaB). Particularly, the antiinflammatory effects of ethyl acetate (EtOAc) and butanol (n-BuOH) extracts were better than those of other extracts. Collectively, these results suggest that EC extracts possess barrier integrity activity, inhibitory activity on cell adhesion and migration to endothelial cells by blocking the activation of NF-kappaB expression and production of TNF-alpha, thereby endorsing its usefulness as therapy for vascular inflammatory diseases. PMID- 20363281 TI - Acute and subacute toxicity of yeast hydrolysate from Saccharomyces cerevisiae. AB - The objective of this study was to obtain data on the safety-in-use of yeast hydrolysate in 10-30 kDa molecular weight as a dietary supplement by assessing its acute and subacute oral toxicity in female and male Sprague-Dawley (SD) rats. The single oral dose of the hydrolysate at 5000 mg/kg did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. In subacute toxicity study, the hydrolysate was administered orally at a dose of 1000 mg/kg/day for a period of 14 days. The satellite group was treated with the hydrolysate at the same dose and the same period and kept for another 14 days after treatment. There were no significant differences in organ weights between control and treated group of both sexes. Hematological analysis and blood chemistry revealed no toxicity effects of Saccharomyces cerevisiae hydrolysate. Pathologically, neither gross abnormalities nor histopathological changes were observed. These results show that the hydrolysate possesses very low toxicity as indicated in SD rat model. PMID- 20363282 TI - A novel trypsin Kazal-type inhibitor from Aedes aegypti with thrombin coagulant inhibitory activity. AB - Kazal-type inhibitors play several important roles in invertebrates, such as anticoagulant, vasodilator and antimicrobial activities. Putative Kazal-type inhibitors were described in several insect transcriptomes. In this paper we characterized for the first time a Kazal unique domain trypsin inhibitor from the Aedes aegypti mosquito. Previously, analyses of sialotranscriptome of A. aegypti showed the potential presence of a Kazal-type serine protease inhibitor, in female salivary glands, carcass and also in whole male, which we named AaTI (A. aegypti trypsin inhibitor). AaTI sequence showed amino acid sequence similarity with insect thrombin inhibitors, serine protease inhibitor from Litopenaeus vannamei hemocytes and tryptase inhibitor from leech Hirudo medicinalis (LDTI). In this work we expressed, purified and characterized the recombinant AaTI (rAaTI). Molecular weight of purified rAaTI was 7 kDa rAaTI presented dissociation constant (K(i)) of 0.15 and 3.8 nM toward trypsin and plasmin, respectively, and it weakly inhibited thrombin amidolytic activity. The rAaTI was also able to prolong prothrombin time, activated partial thromboplastin time and thrombin time. AaTI transcription was confirmed in A. aegypti female salivary gland and gut 3 h and 24 h after blood feeding, suggesting that this molecule can act as anticoagulant during the feeding and digestive processes. Its transcription in larvae and pupae suggested that AaTI may also play other functions during the mosquito's development. PMID- 20363283 TI - More stable structure of wheat germ lipase at low pH than its native state. AB - Wheat germ lipase is a cereal lipase which is a monomeric protein. In the present study we sought to structurally characterize this protein along with equilibrium unfolding in solution. Conformational changes occurring in the protein with varying pH, were monitored by circular dichroism (CD) spectroscopy, fluorescence emission spectroscopy, binding of hydrophobic dye, 1-anilino 8 naphthalenesulfonic acid (ANS) and dynamic light scattering (DLS). Our study showed that acid denaturation of lipase lead to characterization of multiple monomeric intermediates. Native protein at pH 7.0 showed far-UV spectrum indicating mixed structure with both alpha and beta-type of characteristics. Activity of lipase was found to fall on either sides of pH 7.0-8.0. Acid-unfolded state was characterized at pH 4.0 with residual secondary structure, disrupted tertiary spectrum and red-shifted fluorescence spectrum with decreased intensity. Further decrease in pH lead to formation of secondary structure and acid-induced molten globule state was found to be stabilized at pH 1.4, with exposed tryptophan residues and hydrophobic patches. Notably, interesting finding of this study was characterization of acid-induced state at pH 0.8 with higher secondary structure content than native lipase, regain in tertiary spectrum and induction of compact conformation. Although enzymatically inactive, acid-induced state at pH 0.8 was found to be structurally more stable than native lipase, as shown by chemical and thermal denaturation profiles. PMID- 20363284 TI - A novel subclassification for Kunitz proteinase inhibitors from leguminous seeds. AB - Kunitz-type trypsin inhibitors from legume seeds have been characterized structurally. The presence of Cys-Cys in single or double chains shows a new pattern of proteins structurally not so closely related to STI. Therefore, briefly, with regard to cysteine content, plant Kunitz proteinase inhibitors may be classified into four groups: no Cys-Cys at all, one, two and more than two Cys residues. Functional properties and diversity of these proteins are also briefly discussed. PMID- 20363285 TI - Cavin proteins: New players in the caveolae field. AB - Caveolae are specialized lipid microdomains, forming small invaginations in the plasma membrane, known to be implicated in multiple functions including lipid storage, cell signaling and endocytosis. Formation of these wide flask-shaped invaginations is dependent on the expression of a caveolar coat protein, namely caveolin. Until now, the accepted paradigm was that caveolin was the sole and only structural protein of caveolae since its expression was necessary and sufficient to drive caveolae biogenesis. The recent characterizations of PTRF/cavin-1 and subsequently other cavin family members in caveolae formation have highlighted additional levels of complexity in the biogenesis of these plasma membrane invaginations. In this review, recent advances on the role of the different cavin family members in the regulation of caveolae structures as well as potential new functions will be discussed. PMID- 20363286 TI - eNOS phosphorylation in health and disease. AB - Endothelium plays a fundamental role in maintaining the vascular tone by releasing various biochemical factors that modulate the contractile and relaxatory behavior of the underlying vascular smooth muscle, regulation of inflammation, immunomodulation, platelet aggregation, and thrombosis. Endothelium regulates these cellular processes by activating endothelial nitric oxide synthase (eNOS) responsible for nitric oxide (NO) production. eNOS is constitutively expressed in ECs in response to humoral, mechanical or pharmacological stimulus. eNOS activity is regulated mainly by protein-protein interactions and multisite phosphorylations. The phosphorylation state of specific serine, threonine and tyrosine residues of the enzyme plays a pivotal role in regulation of eNOS activity. Perturbations of eNOS phosphorylation have been reported in a number of diseases thereby emphasizing the importance of regulation of eNOS activity. This review summarizes the mechanism of eNOS regulation through multi-site phosphorylation in different pathologies. Attempts have been made to highlight phosphorylation of eNOS at various residues, regulation of the enzyme activity via posttranslational modifications and its implications on health and disease. PMID- 20363287 TI - The functional neuroanatomy of the evolving parent-infant relationship. AB - Infant survival and the development of secure and cooperative relationships are central to the future of the species. In humans, this relies heavily on the evolving early parent-infant social and affective relationship. While much is known about the behavioural and psychological components of this relationship, relatively little is known about the underlying functional neuroanatomy. Affective and social neuroscience has helped to describe the main adult brain networks involved, but has so far engaged very little with developmental findings. In this review, we seek to highlight future avenues for research by providing a coherent framework for describing the parent-infant relationship over the first 18 months. We provide an outline of the evolving nature of the relationship, starting with basic orienting and recognition processes, and culminating in the infant's attainment of higher socio-emotional and cognitive capacities. Key social and affective interactions, such as communication, cooperative play and the establishment of specific attachments propel the development of the parent-infant relationship. We summarise our current knowledge of the developing infant brain in terms of structure and function, and how these relate to the emergent abilities necessary for the formation of a secure and cooperative relationship with parents or other caregivers. Important roles have been found for brain regions including the orbitofrontal, cingulate, and insular cortices in parent-infant interactions, but it has become clear that much more information is needed about the developmental time course and connectivity of these regions. PMID- 20363288 TI - Beta-adrenergic signals regulate adipogenesis of mouse mesenchymal stem cells via cAMP/PKA pathway. AB - The adipogenic capacity of mesenchymal stem cells (MSCs) and the involvement of beta-adrenergic signals in lipolysis and thermogenesis have been well established. However, little is known about the development of beta-adrenergic receptor (beta-AR) systems and the role of beta-adrenergic signals in adipogenic differentiation of MSCs. In this study, we demonstrated that both the mRNA and protein levels of beta2- and beta3-AR were up-regulated following adipogenesis of mouse bone marrow derived MSCs. We also established that beta-AR agonists negatively while antagonists positively affected MSC adipogenesis. Both the beta2 and beta3-AR were involved in MSC adipogenesis, with beta3-AR being the predominant subtype. The effect of beta-ARs on MSC adipogenesis was at least partly mediated via the cAMP/PKA signaling pathway. These findings suggested that MSC is also a target for beta-adrenergic regulation, and beta-adrenergic signaling (major beta3-signaling) plays a role in MSC adipogenesis. PMID- 20363289 TI - Naringenin chalcone improves adipocyte functions by enhancing adiponectin production. AB - Naringenin chalcone is a flavonoid contained in tomato peel. In this study, we investigated its effects on adipocyte functions related to metabolic processes, including adipocytokine production. Naringenin chalcone promoted the gene expression (8.0-fold, p<0.001) and protein secretion (2.2-fold, p<0.001) of adiponectin from 3T3-L1 adipocytes. Reporter gene assays revealed that naringenin enhanced the activity of peroxisome proliferator-activated receptor gamma. DNA microarray experiments and Gene Ontology analysis revealed that naringenin chalcone also up-regulated the genes associated with mitochondrial energy metabolism, reflecting its insulin-sensitizing effects. Conversely, genes in categories such as those for cell adhesion were down-regulated. The expression of one adiponectin receptor, AdipoR2, was also increased (1.8-fold, p<0.01), suggesting that naringenin chalcone could activate the adiponectin pathway through the elevation of both the ligand and its receptor. These results indicate that naringenin chalcone is a potent tomato flavonoid that improves adipocyte metabolic functions and exerts insulin-sensitizing effects by activating an adiponectin-related pathway. PMID- 20363290 TI - Immunological, paracrine and endocrine aspects of testicular immune privilege. AB - Protection of the spermatogenic cells from the host immune response is fundamental to male fertility. Significantly, this protection extends to the tolerance of foreign tissue grafts placed within the testicular environment, a phenomenon that is called 'immune privilege'. This privilege of the testis appears to involve several levels of immune control, encompassing the normal mechanisms of immune tolerance, antigen sequestration behind the blood-testis barrier, reduced immune activation, localised immunosuppression and antigen specific immunoregulation. Central to these regulatory processes are the somatic cells of the testis, particularly the Sertoli cells, and testicular secretions, including androgens, cytokines, peptides and bioactive lipids. Failure of these protective mechanisms, which may be precipitated by trauma, inflammation or infection, or as the consequence of genetic factors, can lead to androgen deficiency, infertility and autoimmunity. PMID- 20363291 TI - HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures. AB - Since the beginning of the highly active antiretroviral therapy (HAART) era, epidemiological evidence indicates an increasing incidence of Alzheimer's (AD) like brain pathology in aging HIV patients. Emerging evidence warns of potential convergent mechanisms underlying HIV- and Abeta-mediated neurodegeneration. We found that HIV-1 Tat B and gp120 promote the secretion of Abeta 1-42 in primary rat fetal hippocampal cell cultures. Our results demonstrate that the variant of Tat expressed by the neurotropic subtype of HIV-1 virus (HIV-1 clade B) specifically induces both the release of amyloidogenic Abeta 1-42 and the accumulation of cell-bound amyloid aggregates. The results of the research rationalize testing of the ability of beta-amyloid aggregation inhibitors to attenuate HIV protein-mediated cognitive deficits in animal models of NeuroAIDS. The long-term goal of the study is to evaluate the potential benefits of anti amyloidogenic therapies for management of cognitive dysfunction in aging HIV-1 patients. PMID- 20363292 TI - Mutant superoxide dismutase 1 overexpression in NSC-34 cells: effect of trehalose on aggregation, TDP-43 localization and levels of co-expressed glycoproteins. AB - Protein inclusions rich in mutant Cu,Zn superoxide dismutase (SOD1) have been found in tissues from patients with familial amyotrophic lateral sclerosis (ALS). Here, the mouse motor neuron-like NSC-34 cell line transiently transfected with human SOD1(G93A) fused to enhanced green fluorescent protein exhibited aggregates contrary to cells overexpressing wild-type human SOD1. The aggregates were immunoreactive for ubiquitin but not for the TAR DNA binding protein (TDP-43) that was found in the nucleus. These characteristics mimicked the pathology of mutant SOD1 associated familial ALS. Aggregate formation and mutant SOD1 detergent insolubility were significantly decreased in the presence of millimolar concentrations of trehalose possibly due to its capacity to induce autophagy or to its properties as chemical chaperone. Mutant SOD1, aggregated and non aggregated, caused decreased levels of concomitantly expressed secretory (beta trace protein and erythropoietin) and plasma membrane (L1 cell adhesion molecule) glycoproteins, which were not due to their intracellular accumulation. These cells may be used to study mechanisms of pathogenesis associated with ALS and to test potential therapeutic compounds. PMID- 20363293 TI - Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze. AB - Marijuana discontinuation has been recently reported to be anxiogenic in humans, which may predict relapse. Limited animal research has been carried out to model this withdrawal-associated negative affect. The current study sought to investigate the potential anxiety-like effects of cannabinoid withdrawal in mice. Male ICR mice were injected s.c. with delta9-tetrahydrocannabinol (THC) at 10mg/kg or vehicle once daily for 10 days. To precipitate withdrawal, the cannabinoid CB1 antagonist SR141716 (0.3, 1.0, or 3.0mg/kg) or vehicle was administrated i.p. 4h following the last THC or vehicle treatment. Thirty minutes later, mice were tested on the elevated plus-maze (EPM) for 5min. SR141716 did not significantly change EPM behaviors in vehicle-treated mice. In contrast, SR141716 precipitated a reduction in exploration of the open arms of EPM in mice repeatedly treated with THC vs vehicle. At 3.0mg/kg, SR141716 significantly reduced % open arm entries of the total arm entries, % open arm time of total time in arms, and the absolute time spent in open arms. No significant differences in the number of closed or total arm entries were observed, indicating that the behavioral changes were not due to altered motor activity. Collectively, the present results constitute the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice. This animal model may help to identify the mechanisms that contribute to adaptations in the neuronal circuitry of the brain that are expressed as emotional symptoms of cannabinoid withdrawal. PMID- 20363294 TI - The effects of dopaminergic drugs in the ventral hippocampus of rats in the nicotine-induced anxiogenic-like response. AB - Nicotine an active alkaloid of tobacco has dopaminergic properties. The drug alters anxiety-like behavior in rodents. Ventral hippocampus (VHC) may be a site for modulation of anxiety-like behaviors. The possible involvement of ventral hippocampal dopaminergic receptor mechanism in the nicotine influence on anxiogenic-like response has been investigated in the present study. The effects of apomorphine, sulpiride and SCH23390 on nicotine response in elevated plus maze in rats have been investigated. Intraperitoneal administration of nicotine (0.6mg/kg) decreased percentage of open arm time (%OAT) but not percentage of open arm entries (%OAE) and locomotor activity, indicating an anxiogenic-like response. Intra-hippocampal injection (intra-VHC) of apomorphine, a D(1)/D(2) dopamine receptor agonist (0.1 and 0.2microg/rat) also caused anxiogenic-like effects, but the drug blocked that of nicotine. Intra-VHC administration of the D(2) receptor antagonist, sulpiride (1, 2.5 and 5microg/rat) or the D(1) receptor antagonist, SCH23390 (0.01, 0.1 and 1microg/rat) did not elicit any response. However, pretreatment with sulpiride (1microg/rat) or SCH23390 (0.1microg/rat) decreased nicotine's effect. The results may indicate a modulatory effect for the D(1) and D(2) dopamine receptors of VHC in the anxiogenic-like response induced by nicotine. PMID- 20363295 TI - X-ray structures of ferritins and related proteins. AB - Ferritins are members of a much larger superfamily of proteins, which are characterised by a structural motif consisting of a bundle of four parallel and anti-parallel alpha helices. The ferritin superfamily itself is widely distributed across all three living kingdoms, in both aerobic and anaerobic organisms, and a considerable number of X-ray structures are available, some at extremely high resolution. We describe first of all the subunit structure of mammalian H and L chain ferritins and then discuss intersubunit interactions in the 24-subunit quaternary structure of these ferritins. Bacteria contain two types of ferritins, FTNs, which like mammalian ferritins do not contain haem, and the haem-containing BFRs. The characteristic carboxylate-bridged di-iron ferroxidase sites of H chain ferritins, FTNs and BFRs are compared, as are the potential entry sites for iron and the 'nucleation' site of L chain ferritins. Finally we discuss the three-dimensional structures of the 12-subunit bacterial Dps (DNA-binding protein from starved cells) proteins as well as their intersubunit di-iron ferroxidase site. PMID- 20363296 TI - The Mossbauer and magnetic properties of ferritin cores. AB - BACKGROUND: Mossbauer and magnetization measurements, singly or in combination, extract detailed information on the microscopic or internal magnetism of iron based materials and their macroscopic or bulk magnetization. The combination of the two techniques affords a powerful investigatory probe into spin relaxation processes of nanosize magnetic systems. The ferritin core constitutes a paradigm of such nano-magnetic system where Mossbauer and magnetization studies have been broadly combined in order to elucidate its composition, the initial steps of iron nucleation and biomineralization, particle growth and core-size distribution. In vivo produced and in vitro reconstituted wild-type and variant ferritins have been extensively studied in order to elucidate structure/function correlations and ferritin's role in iron overloading or neurodegenerative disorders. SCOPE OF REVIEW: Studies on the initial stages of iron biomineralization, biomimetic synthetic analogues and ferrous ion retention within the ferritin core are presented. The dynamical magnetic properties of ferritin by Mossbauer and magnetization measurements are critically reviewed. The focus is on experiments that reveal the internal magnetic structure of the ferritin core. Novel magnetic measurements on individual ferritin molecules via AFM and nanoSQUID investigations are also mentioned. MAJOR CONCLUSIONS: A complex two-phase spin system is revealed due to finite-size effects and non-compensated spins at the surface of the anti-ferromagnetic ferritin core. Below the blocking temperature surface spins participate in relaxation processes much faster than those associated with collective magnetic excitations of interior spins. GENERAL SIGNIFICANCE: The studies reviewed contribute uniquely to the elucidation of the spin-structure and spin-dynamics of anti-ferromagnetic nanolattices and their possible applications to nano/bio-technology. PMID- 20363297 TI - The parabrachial nucleus is a critical link in the transmission of short latency nociceptive information to midbrain dopaminergic neurons. AB - Many dopaminergic neurons exhibit a short-latency response to noxious stimuli, the source of which is unknown. Here we report that the nociceptive-recipient parabrachial nucleus appears to be a critical link in the transmission of pain related information to dopaminergic neurons. Injections of retrograde tracer into the substantia nigra pars compacta of the rat labelled neurons in both the lateral and medial parts of the parabrachial nucleus, and intra-parabrachial injections of anterograde tracers revealed robust projections to the pars compacta and ventral tegmental area. Axonal boutons were seen in close association with tyrosine hydroxylase-positive (presumed dopaminergic) and negative elements in these regions. Simultaneous extracellular recordings were made from parabrachial and dopaminergic neurons in the anaesthetized rat, during the application of noxious footshock. Parabrachial neurons exhibited a short latency, short duration excitation to footshock while dopaminergic neurons exhibited a short-latency inhibition. Response latencies of dopaminergic neurons were reliably longer than those of parabrachial neurons. Intra-parabrachial injections of the local anaesthetic lidocaine or the GABA(A) receptor antagonist muscimol reduced tonic parabrachial activity and the amplitude (and in the case of lidocaine, duration) of the phasic response to footshock. Suppression of parabrachial activity with lidocaine reduced the baseline firing rate of dopaminergic neurons, while both lidocaine and muscimol reduced the amplitude of the phasic inhibitory response to footshock, in the case of lidocaine sometimes abolishing it altogether. Considered together, these results suggest that the parabrachial nucleus is an important source of short-latency nociceptive input to the dopaminergic neurons. PMID- 20363298 TI - Identification of a FOXA-dependent enhancer of human alcohol dehydrogenase 4 (ADH4). AB - Human alcohol dehydrogenase 4 (ADH4) is one of the key enzymes involved in the metabolism of alcohol. ADH4 is highly expressed in the liver, and previous studies have revealed several cis-acting elements in the proximal promoter region. In this study we have identified a distal upstream enhancer, 4E, of ADH4. In HepG2 human hepatoma cells, 4E increased the activity of an ADH4 basal promoter by 50-fold. 4E was cell-specific, as no enhancer activity was detected in a human lung cell line, H1299. We have narrowed the enhancer activity to a 565 bp region and have identified multiple liver-enriched transcription factor binding sites in the region. By electrophoretic mobility shift assays, we confirmed binding of FOXA proteins to these sites. Site-directed mutagenesis studies demonstrated that sites 1 and 4 have the biggest effect on enhancer function, and mutations in multiple sites have multiplicative effects. We also studied the effects of three variations in the minimal enhancer region. Two variations had a significant effect on enhancer activity, decreasing the activity to 0.6-fold, while one had small but significant effect. The differences in the functional activity in different haplotypes suggest that this region could play an important role in the risk for alcoholism. PMID- 20363299 TI - Mechanical and geometric property characterization of dry-coated tablets with contact ultrasonic techniques. AB - A dry-coated tablet is a solid dosage form with a controlled drug-release system, which consists of a core and an outer layer. The accuracy of its geometric (e.g. the outer layer wall and core thicknesses) and mechanical properties (e.g. Young's moduli and mass densities of associated materials) could be crucial to its therapeutic and structural functions. The objective of current study is to develop a non-destructive technique for determining the geometric and mechanical properties of dry-coated tablets. Two contact ultrasonic techniques (i.e. pitch catch and pulse-echo measurement modes) are employed and the properties of all the structural components of a set of experimental tablets are measured and reported. The thicknesses of the outer layers of the sample tablets are used to obtain the eccentricity of the core tablets. The two approaches are compared for their effectiveness in obtaining these properties of the sample dry-coated tablets. The thicknesses of the outer layers obtained with the proposed approach and with the direct (destructive) measurements are also compared. A good agreement is found; there is an approximately 2% difference. The eccentricity and concentricity of a set of tablets are determined and it is concluded that the observed consistent anomaly in eccentricity can be attributed to the same root cause and its correction can be achieved by control input based on monitoring data. Potential of the approach for in-die real-time monitoring of compaction presses and its PAT (Process Analytical Technology) applications for the pharmaceutical manufacturing are also discussed. PMID- 20363300 TI - Silica nanoparticle coated liposomes: a new type of hybrid nanocapsule for proteins. AB - A hybrid silica-liposome nanocapsule system containing insulin has been developed and the encapsulation, protection and release properties are evaluated. The formulation strategy is based on using insulin-loaded 1,2-dipalmitoyl-sn-glycero 3-phosphocholine and cholesterol liposomes as a template for the deposition of inert silica nanoparticles. The influence of formulation and process variables on particle size, zeta potential and liposome entrapment of insulin is reported. The ability to protect against lipolytic degradation and sustain insulin release in vitro in simulated GI conditions is also reported. Depending on the concentration and charge ratio of liposomes and silica nanoparticles, nanoparticle coated liposomes with varied size and zeta potential were obtained with an insulin entrapment efficiency of 70%. The silica nanoparticle coating protected liposomes against degradation by digestive enzymes in vitro; the release rate of insulin from silica coated liposomes was reduced in comparison to uncoated liposomes. Thus the liposomal release kinetics and stability can be controlled by including a specifically engineered nanoparticle layer. Silica nanoparticle-liposomes hybrid nanocapsules show promise as a delivery vehicle for proteins and peptides. PMID- 20363301 TI - The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient. AB - The aim of the present study was to investigate the effect of crystallising mannitol from different binary mixtures of acetone/water on the resultant physical properties and to determine the effects of any changes on in vitro aerosolisation performance, when the different mannitol crystals were used as a carrier in dry powder inhaler formulations containing salbutamol sulphate. Mannitol particles were crystallised under controlled conditions by dissolving the sugar in water and precipitating the sugar using binary mixtures of acetone/water in different percentages as anti-solvent media. For comparison purposes the physical properties and deposition behaviour of commercially available mannitol were also studied. SEM showed that all crystallised mannitol particles were more elongated than the commercial mannitol. Solid state studies revealed that commercial mannitol and mannitol crystallised using acetone in the presence of 10-25% v/v water as anti-solvent was beta-polymorphic form whereas mannitol crystallised in the presence of a small amount of water (0-7.5%) was the alpha-form. All the crystallised mannitol samples showed poor flowability. Nevertheless, the powdered crystallised mannitol and commercial samples were blended with salbutamol in the ratio 67.5:1. The aerosolisation performance of the formulations containing the engineered mannitol (evaluated using Multi Stage Liquid Impinger) was considerably better than that of the commercial mannitol formulation (the fine particle fraction was increased from 15.42% to 33.07 43.99%, for the formulations containing crystallised mannitol). Generally, carriers having a high tapped density and high fraction of fine carrier particles produced a high FPF. The improvement in the DPI performance could be attributed to the presence of elongated carrier particles with smooth surfaces since these are believed to have less adhesive forces between carrier and the drug resulting in easier detachment of the drug during the inhalation. PMID- 20363302 TI - Solubility enhancement of hydrophobic compounds by cosolvents: role of solute hydrophobicity on the solubilization effect. AB - Drug solubilization is an important aspect of drug development. We investigate the relationship between solute hydrophobicity on the solubilization properties of water-cosolvent mixtures. The solubilization in water-cosolvent mixtures of seven chemically unrelated drugs was determined. The set of solutes included hydrocortisone, sulfanilamide, acetophenetidine, benzocaine, indomethacin, thymol and ibuprofen. Two sets of water-cosolvent mixtures were used in the study. A group of polar cosolvents consisting of three aliphatic alcohols, and a group of the less polar cosolvents NMP, tetraglycol and labrasol. The hydrophobicity of the drug has a direct impact on the solubilization obtained in the water cosolvent mixtures. However, the role of hydrophobicity is different in the case of the polar cosolvents compared with the less polar ones. In polar cosolvents, the solubilization behavior is typical of polarity match, where the collective trend of solubility enhancement decreases as the activity coefficient of the solute in the solvent mixture increases. The result is a linear profile comprising the combined data of all solutes and all solvents. On the other hand, while the less polar cosolvents exhibit greater positive deviations from the log linear cosolvency model, the collective solubility enhancement in these systems exhibits no readily discernible pattern. However, by taking into account the hydrophobicity of the solutes, a systematic effect becomes clearly apparent. In this case, the hydrophobicity of the solute demarcates its region in the solubilization profile. PMID- 20363303 TI - Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer. AB - Cisplatin (CDDP) intravenous treatments suffer several dose-limiting toxicity issues. Hyaluronan (HA), a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. An alteration in input rate and administration route through pulmonary delivery of hyaluronan-cisplatin (HA-Pt) conjugate may increase local lung CDDP concentrations and decrease systemic toxicity. Sprague-Dawley rats were split into four groups: i.v. CDDP (3.5 mg/kg), i.v. HA-Pt conjugate (3.5 mg/kg equivalent CDDP), lung instillation CDDP and lung instillation HA-Pt conjugate. Total platinum level in the lungs of the HA-Pt lung instillation group was 5.7-fold and 1.2-fold higher than the CDDP intravenous group at 24 and 96 h, respectively. A 1.1-fold increase of Pt accumulation in lung draining nodes for the HA-Pt lung instillation group was achieved at 24h relative to the CDDP i.v. group. In the brain and kidneys, the CDDP i.v. group had higher tissue/plasma ratios compared to the HA-Pt lung instillation group. Augmented tissue distribution from CDDP i.v. could translate into enhanced tissue toxicity compared to the altered input rate and distribution of the intrapulmonary nanoformulation. In conclusion, a local pulmonary CDDP delivery system was developed with increased platinum concentration in the lungs and draining nodes compared to i.v. therapy. PMID- 20363304 TI - Effect of surfactant concentration on transdermal lidocaine delivery with linker microemulsions. AB - A limited number of studies have been conducted to investigate the effect of surfactant concentration on microemulsion-mediated transdermal transport. Some studies suggest that increasing surfactant concentration reduces the partition of the active in the skin, and the overall transport. Other studies suggest that increasing surfactant concentration improves mass transport across membranes by increasing the number of "carriers" available for transport. To decouple these partition and mass transport effects, a three-compartment (donor, skin, receiver) mass balance model was introduced. The model has three permeation parameters, the skin-donor partition coefficient (K(sd)), the donor-skin mass transfer coefficient (k(ds)) and the skin-receiver mass transfer coefficient (k(sr)), also known as skin permeability. The model was used to fit the permeation profile of lidocaine formulated in oil-in-water (Type I) and water-in-oil (Type II) lecithin linker microemulsions. The results show that surfactant concentration has a relatively minor effect on the mass transfer coefficients, suggesting that permeation enhancement via disruption of the structure of the skin is not a relevant mechanism in these lecithin-linker microemulsions. The most significant effect was the increase in the concentration of lidocaine in the skin with increasing surfactant concentration. For Type I systems such increase in lidocaine concentration in the skin was linked to the increase in lidocaine solubilization in the microemulsion with increasing surfactant concentration. For Type II systems, the increase in lidocaine concentration in the skin was linked to the increase in skin-donor partition. A surfactant-mediated absorption/permeation mechanism was proposed to explain the increase in lidocaine concentration in skin with increasing surfactant concentration. The penetration profiles of hydrophobic and amphiphilic fluorescence probes are consistent with the proposed mechanism. PMID- 20363305 TI - Design and evaluation of micellar nanocarriers for 17-allyamino-17 demethoxygeldanamycin (17-AAG). AB - 17-Allyamino-17-demethoxygeldanamycin (17-AAG) is a potent anticancer agent currently undergoing phases I and II clinical trials. However, the clinical development of 17-AAG has been hindered by its poor aqueous solubility and hepatotoxicity. This study aimed to devise novel micellar nanocarriers for 17-AAG that improve its solubility and retain the incorporated drug for a prolonged period of time. We have found that 1,2-distearoyl-sn-glycero-3 phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]/D-alpha-tocopheryl polyethylene glycol 1000 (PEG-DSPE/TPGS) mixed micelles (at a 1:2 molar ratio) can deliver 17-AAG at clinically relevant doses. By modulating the concentrations of micelle-forming copolymers, the burst release of 17-AAG from PEG-DSPE/TPGS mixed micelles was substantially reduced with a release half-life up to about 8h. Our (1)H NMR spectroscopy results revealed that the incorporation of TPGS into PEG-DSPE micelles restricted internal molecular motions of copolymers in both the corona and core regions of the micelles, leading to the delayed drug release. Cytotoxicity of 17-AAG formulated in PEG-DSPE/TPGS mixed micelles against human ovarian cancer SKOV-3 cells was comparable to that of free 17-AAG. 17-AAG-loaded PEG-DSPE/TPGS mixed micelles may offer a promising alternative to the current 17 AAG formulations for the treatment of solid tumors. PMID- 20363306 TI - Effect of lipopolysaccharide on P-glycoprotein-mediated intestinal and biliary excretion of rhodamine123 in rats. AB - The effects of lipopolysaccharide (LPS) on the ileal and biliary excretion of rhodamine123 were investigated in rats at different times after intraperitoneal (i.p.) injection (1 mg/kg and 5 mg/kg of body weight). P-gp protein decreased 8h after injection of LPS and returned to the control level 24h after i.p. injection of LPS in the ileum. There was a marked decrease in the expression level of mdr1a mRNA in the ileum and liver 8h after i.p. injection of LPS when compared with the control condition. Also, the ileal and biliary clearance of rhodamine123 significantly decreased 8h after i.p. injection of LPS, but returned to the control levels 24h after i.p. injection of LPS. These results suggest that LPS induced decreases in P-gp-mediated ileal and biliary excretion of rhodamine123 were probably due to impaired P-gp-mediated transport ability. The levels of iNOS and IL-1beta mRNA in the ileum and liver increased 2 and 8h after i.p. injection of LPS, respectively, and returned to the control levels 24h after injection of LPS. These findings suggest that LPS markedly decreases P-gp-mediated ileal and biliary excretion of rhodamine123, probably by partly decreasing the expression of P-gp protein levels, likely due to increased lipid peroxidation levels through iNOS mRNA and inflammatory mediators such as IL-1beta. PMID- 20363307 TI - Enhanced gene transfection efficiency by polyamidoamine (PAMAM) dendrimers modified with ornithine residues. AB - Aim of the study was to prepare and to evaluate gene transfection efficiency and cytotoxicity of the ornithine-conjugated PAMAMG4 dendrimers. Ornithine-conjugated PAMAMG4 dendrimers were prepared by Fmoc synthesis. A comparative gene transfection study between PAMAMG4 dendrimers and the surface modified dendrimers was conducted in HEK 293T, GM7373 and NCI H157G cell lines. Effect of excess of ornithine (100muM) on transfection efficiency of the ornithine-conjugated PAMAMG4 dendrimers was investigated in separate experiment. Cytotoxicity of the dendriplexes was tested in HEK 293T cells by MTT assay. (1)H NMR and MALDI-TOF spectral analysis showed that about 60 molecules of ornithine (PAMAMG4-ORN60) were conjugated to a PAMAMG4 dendrimer. Preliminary studies indicated that dendriplexes at charge ratio (N/P 10) show higher transfection efficiency and presence of serum does not affect the transfection efficiency of the dendriplexes. Transfection efficiency of PAMAMG4-ORN60 dendriplexes was slightly higher in cancer cells (NCI H157G) as compared to HEK 293T cells. Transfection efficiency of the PAMAMG4-ORN60 dendrimers decreased in presence of excess of ornithine while there was no effect on the parent PAMAMG4 dendrimers. Cytotoxicity assay has shown that PAMAMG4-ORN60 dendriplexes at N/P 10 were safe at concentrations 99%; specific activity 2x10(8)IU/mg; stability - more than two years as a lyophilized powder and more than two months in solution at 4 degrees C. PMID- 20363330 TI - Recovery of recombinant zebrafish p53 protein from inclusion bodies and its binding activity to p53 mRNA in vitro. AB - p53 protein is an important regulation factor that can bind to p53 mRNA to regulate its translation in human and murine. To determine if a similar interaction exists in zebrafish and if the interaction affects zebrafish development, we cloned and expressed p53 protein from zebrafish in Escherichia coli. Soluble p53 protein with high purity was successfully obtained using the optimized renaturation approach. Results of a UV-crosslinking experiment and immunoprecipitation:RT-PCR analysis confirmed that the purified p53 protein could bind specifically to its cognate mRNA. Our results suggest that selecting a suitable buffer is important for renaturing p53 protein from inclusion bodies. We also demonstrated a specific interaction between p53 and it own RNA in zebrafish. Measurement of the binding activity may be a useful approach for identifying the activity of recombinant p53 protein in vitro. PMID- 20363331 TI - Cloning, expression and efficient refolding of carbohydrate-peptide mimicry recognizing single chain antibody 2D10. AB - Carbohydrate-peptide mimicry was found to be manifested through the cross reactivity of an anti-mannopyranoside monoclonal antibody 2D10 (mAb-2D10) with YPY motif containing 12-mer peptide (DVFYPYPYASGS). Such multiple binding options for a monoclonal antibody could emanate from the possible flexibility of the antigen combining site. To address the molecular details of this phenomenon, single chain antibody (scFv) containing the antigen combining variable domain of mAb-2D10 was constructed. The present work describes the cloning, expression, purification and efficient refolding of scFv-2D10 and its His(6) tag fusion variants. The scFv expressed poorly in soluble/active form in the periplasmic compartment and concurrently exhibited higher tendency towards accumulation in inclusion bodies inside the Escherichia coli cytoplasm. The scFv was refolded from the inclusion bodies with approximately 68% yield using a previously described protocol which employed concomitant removal of the chaotropic and oxidizing reagents along with the additives. However, their differential removal, as described in the present report resulted in approximately 97% effective yield of the soluble scFv-2D10, an increase of 42%. The binding kinetics of the refolded scFv for both the mimicking ligands was examined using surface plasmon resonance experiments. The scFv-2D10 exhibited binding affinities similar to those reported for mAb-2D10 (IgG) showing that the modifications introduced in the refolding protocol have facilitated efficient preparation of active 2D10 scFv. PMID- 20363332 TI - Recombinant production of bioactive human TNF-alpha by SUMO-fusion system--high yields from shake-flask culture. AB - Tumor necrosis factor (TNF-alpha) inhibitors, used for the treatment of common inflammatory diseases, currently belong among the most important biotechnologically produced pharmaceuticals. So far four TNF-alpha antagonists have been approved by regulatory authorities for defined subsets of applications. Furthermore, numerous approaches are being taken to develop new protein-based pharmaceuticals and to broaden their application areas in the treatment of TNF alpha -related diseases. Both the fundamental understanding of disease-related TNF-alpha activity and the subsequent development of corresponding drug candidates demand the availability of large amounts of TNF-alpha as a bioactive protein. We have therefore established a protocol for the rapid high-level synthesis of recombinant human TNF-alpha in Escherichia coli shake-flask cultures and the subsequent purification of the mature protein. Using the advantages of SUMO-fusion technology we were able to produce protein with an authentic N terminus in high yield. Two immobilized metal ion-affinity chromatography steps with a protease cleavage step in between and subsequent size-exclusion chromatography were utilized to purify the protein. The protein was obtained from the last chromatography step as a trimer, while purity was at least 96% as estimated by SDS-PAGE. The identity of the protein was confirmed by MALDI-TOF mass spectrometry. Recombinant mature TNF-alpha was correctly folded as assessed by CD spectroscopy and its biological activity was confirmed by an L929 cell assay. PMID- 20363333 TI - High-efficient expression, refolding and purification of functional recombinant C terminal fragment of human alpha-fetoprotein. AB - Human alpha-fetoprotein (hAFP) is an oncofetal protein which is a common cancer marker. Conjugates of native hAFP with different cytostatic agents inhibit growth of cancer cells in vivo and in vitro. The hAFP interacts with its receptor (AFPR) on the surface of cancer cells via its C-terminal domain. The aim of this work was to develop a highly efficient expression system in Escherichia coli and efficient refolding procedure for the recombinant C-terminal fragment of hAFP (rAFP-Cterm) and to characterize its functional properties. C-terminal fragment of hAFP (rAFP-Cterm) comprising amino acids from 404 to 609 was expressed in E. coli BL21 (DE3) strain with high yield. High efficient purification and refolding procedures were developed giving yield of refolded protein about 80% with purity about 95%. The refolded rAFP-Cterm bound specifically with cancer cells carrying AFPR and was accumulated by them with the same efficiency as native hAFP. This rAFP-Cterm can be used as a vehicle for the targeted delivery of drugs to cancer cells. PMID- 20363334 TI - Spectral-based automatic labeling and refining of human cortical sulcal curves using expert-provided examples. AB - We present a spectral-based method for automatically labeling and refining major sulcal curves of a human cerebral cortex. Given a set of input (unlabeled) sulcal curves automatically extracted from a cortical surface and a collection of expert provided examples (labeled sulcal curves), our objective is to identify the input major sulcal curves and assign their neuroanatomical labels, and then refines these curves based on the expert-provided example data, without employing any atlas-based registration scheme as preprocessing. In order to construct the example data, neuroanatomists manually labeled a set of 24 major sulcal curves (12 each for the left and right hemispheres) for each individual subject according to a precise protocol. We collected 30 sets of such curves from 30 subjects. Given the raw input sulcal curve set of a subject, we choose the most similar example curve to each input curve in the set to label and refine the latter according to the former. We adapt a spectral matching algorithm to choose the example curve by exploiting the sulcal curve features and their relationship. The high dimensionality of sulcal curve data in spectral matching is addressed by using their multi-resolution representations, which greatly reduces time and space complexities. Our method provides consistent labeling and refining results even under high variability of cortical sulci across the subjects. Through experiments we show that the results are comparable in accuracy to those done manually. Most output curves exhibited accuracy values higher than 80%, and the mean accuracy values of the curves in the left and the right hemispheres were 84.69% and 84.58%, respectively. PMID- 20363335 TI - DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma. AB - OBJECT: Intrinsic diffuse brainstem tumors and demyelinating diseases primarily affecting the brainstem can share common clinical and radiological features, sometimes making the diagnosis difficult especially at the time of first clinical presentation. To explore the potential usefulness of new MRI sequences in particular diffusion tensor imaging fiber tracking in differentiating these two pathological entities, we review a series of brainstem tumors and demyelinating diseases treated at our institution. MATERIAL AND METHODS: The clinical history including signs and symptoms and MRI findings of three consecutive demyelinating diseases involving the brainstem that presented with diagnostic uncertainty and three diffuse intrinsic brainstem tumors were reviewed, along with a child with a supratentorial tumor for comparison. Fiber tracking of the pyramidal tracts was performed for each patient using a DTI study at the time of presentation. Additionally Fractional Anisotropy values were calculated for each patient in the pons and the medulla oblongata. RESULTS: Routine MR imaging was unhelpful in differentiating between intrinsic tumor and demyelination. In contrast, retrospective DTI fiber tracking clearly differentiated the pathology showing deflection of the pyramidal tracts posteriorly and laterally in the case of intrinsic brainstem tumors and, in the case of demyelinating disease, poorly represented and truncated fibers. Regionalized FA values were variable and of themselves were not predictive either pathology. CONCLUSION: DTI fiber tracking of the pyramid tracts in patients with suspected intrinsic brainstem tumor or demyelinating disease presents two clearly different patterns that may help in differentiating between these two pathologies when conventional MRI and clinical data are inconclusive. PMID- 20363336 TI - Differential category learning processes: The neural basis of comparison-based learning and induction. AB - Findings from numerous studies suggest that multiple neural systems are involved in category learning. Specifically, it is often argued that acquiring a representation of different category structures (e.g., rule-based vs. prototype based representation) involves different computational challenges, which are resolved by different neural circuitries in the human brain. Here we present an alternative approach for studying neural mechanisms of category learning: We refer to the idea that any category learning task involves mapping common features shared by same-category members, distinctive features discriminating members of different categories, or both. We argue that since these processes are psychologically and computationally distinct, they differ in their usability for category learning. Our participants learned novel categories of complex visual stimuli by comparing either pairs of objects from the same novel category or pairs of objects from different categories. Object pairs were chosen so that the objective amount of information they contained was identical in the two category learning conditions, equally enabling learning the predefined objective category structure. We find that the neural circuitry involved in detecting important between-categories differences is associated mainly with the dorsal striatum (bilaterally) and the right hippocampus. On the other hand, mapping within category similarities and differences is restricted to high-level visual brain areas. We suggest that multiple neural mechanisms are involved in category learning enabling us to face different computational challenges associated with different basic types of induction processes that differ in their usability for learning different category structures. PMID- 20363337 TI - Functional network interactions during sensorimotor synchronization in musicians and non-musicians. AB - Precise timing as determined by sensorimotor synchronization is crucial for a wide variety of activities. Although it is well-established that musicians show superior timing as compared to non-musicians, the neurophysiological foundations in particular the underlying functional brain network - remain to be characterized. To this end, drummers, professional pianists and non-musicians performed an auditory synchronization task while neuromagnetic activity was measured using a 122-channel whole-head magnetoencephalography (MEG) system. The underlying functional brain network was determined using the beamformer approach Dynamic Imaging of Coherent Sources (DICS). Behaviorally, drummers performed less variably than non-musicians. Neuromagnetic analysis revealed a cerebello-thalamo cortical network in all subjects comprising bilateral primary sensorimotor cortices (S1/M1), contralateral supplementary motor and premotor regions (SMA and PMC), thalamus, posterior parietal cortex (PPC), ipsilateral cerebellum and bilateral auditory cortices. Stronger PMC-thalamus and PPC-thalamus interactions at alpha and beta frequencies were evident in drummers as compared to non musicians. In professional pianists stronger PMC-thalamus interaction as compared to non-musicians at beta frequency occurred. The present data suggest that precise timing is associated with increased functional interaction within a PMC thalamus-PPC network. The PMC-thalamus connectivity at beta frequency might be related to musical expertise, whereas the PPC-thalamus interaction might have specific relevance for precise timing. PMID- 20363339 TI - Evolution of the nocturnal Nearctic Sphaeropthalminae velvet ants (Hymenoptera: Mutillidae) driven by Neogene orogeny and Pleistocene glaciation. AB - The influence of historical climatic and geological changes on patterns of species diversification was investigated in a widely distributed group of North American nocturnal mutillids (Hymenoptera: Mutillidae: Sphaeropthalminae), with particular focus on Pleistocene glacial cycles and earlier patterns of Neogene mountain building. We collected molecular data from two nuclear intergenic regions (internal transcribed spacer regions 1 and 2; approximately 2600 bp in total) to produce the first phylogeny of nocturnal Nearctic mutillids. Bayesian inference of the combined data returned a well-resolved tree with posterior probabilities of over 95% for most nodes. This tree suggested the monophyly of the nocturnal, primarily Nearctic, Sphaeropthalminae genera, but the paraphyly of the three largest genera (Odontophotopsis, Photomorphus and Sphaeropthalma). Dates of species divergences were obtained using r8s (PL and NPRS) and BEAST with the date of Dominican amber set at three different dates (15 Ma, 20 Ma, and 45 Ma) to account for uncertainty in the fossil age. The derived dates ranged from the Pleistocene to the Middle Miocene, suggesting that both recent Pleistocene glaciation cycles and older orogenic events, albeit to a somewhat greater extent, were both causes of major diversification in western North America. Examination of other phylogeographical studies using North American desert taxa indicated that diversification patterns are explained by either mountain building or Pleistocene climate change, depending on the taxa in question. PMID- 20363340 TI - Inference of molecular homology and sequence alignment by direct optimization. AB - That homologies exist and can be recognized and discovered is of central importance to comparative and evolutionary biology. Traditionally, homology assessment for both molecular and morphological data has been treated as a two step process involving the generation of a proposition of homology and then the evaluation of that hypothesis through the test of congruence in a phylogenetic analysis. An alternative phylogenetic method, direct optimization, combines these into a one-step process in which positional homology and cladograms are co estimated simultaneously. Here we examine the use of the term "homology" as it is applied to molecular data, and critique the concept of molecular homology one must accept if cladograms are to be interpreted as phylogenetic estimates. The test of congruence alone cannot be used to determine homologous (historically identical) features, and character analysis and the proposition of primary homology hypotheses is the only procedure that can identify correspondences between features justified as retaining phylogenetic information. The practical ramifications for phylogenetic analysis, such as data exclusion and the interpretation of tree-like diagrams as phylogenies, are discussed. PMID- 20363338 TI - Evolution of Conus peptide toxins: analysis of Conus californicus Reeve, 1844. AB - Conus species are characterized by their hyperdiverse toxins, encoded by a few gene superfamilies. Our phylogenies of the genus, based on mitochondrial genes, confirm previous results that C. californicus is highly divergent from all other species. Genetic and biochemical analysis of their venom peptides comprise the fifteen most abundant conopeptides and over 50 mature cDNA transcripts from the venom duct. Although C. californicus venom retains many of the general properties of other Conus species, they share only half of the toxin gene superfamilies found in other Conus species. Thus, in these two lineages, approximately half of the rapidly diversifying gene superfamilies originated after an early Tertiary split. Such results demonstrate that, unlike endogenously acting gene families, these genes are likely to be significantly more restricted in their phylogenetic distribution. In concordance with the evolutionary distance of C. californicus from other species, there are aspects of prey-capture behavior and prey preferences of this species that diverges significantly from all other Conus. PMID- 20363341 TI - The phylogenetic position and speciation dynamics of the genus Perdix (Phasianidae, Galliformes). AB - The nuclear gene (c-mos) and mitochondrial genes (CYT B and ND2) sequences, representing 44 phasianid species and 26 genera (mainly distributed in China), were used to study the phylogeny of the genus Perdix, which comprises three partridge species. Maximum parsimony and Bayesian methods were employed, and the analysis of mitochondrial sequence data and the combined dataset showed that Perdix is specifically related either to typical pheasants or to Ithaginis. Phylogenetic trees also indicated that: (1) Perdix is monophyletic; (2) the Tibetan partridge (Perdix hodgsoniae) has been consistently placed as basal to all other Perdix, and the Daurian partridge (Perdix dauuricae) is placed sister to gray partridge (Perdix perdix); (3) the Daurian partridge subspecies przewalskii and Tibetan partridge subspecies hodgsoniae are basal to other subspecies in their species clade, respectively. Speciation in Perdix was likely promoted by the late Pliocene/early Pleistocene intensive uplift of the Tibetan Plateau and by Pleistocene glaciations. PMID- 20363342 TI - Origin of the Y genome in Elymus and its relationship to other genomes in Triticeae based on evidence from elongation factor G (EF-G) gene sequences. AB - It is well known that Elymus arose through hybridization between representatives of different genera. Cytogenetic analyses show that all its members include the St genome in combination with one or more of four other genomes, the H, Y, P, and W genomes. The origins of the H, P, and W genomes are known, but not for the Y genome. We analyzed the single copy nuclear gene coding for elongation factor G (EF-G) from 28 accessions of polyploid Elymus species and 45 accessions of diploid Triticeae species in order to investigate origin of the Y genome and its relationship to other genomes in the tribe Triticeae. Sequence comparisons among the St, H, Y, P, W, and E genomes detected genome-specific polymorphisms at 66 nucleotide positions. The St and Y genomes are relatively dissimilar. The phylogeny of the Y genome sequences was investigated for the first time. They were most similar to the W genome sequences. The Y genome sequences were placed in two different groups. These two groups were included in an unresolved clade that included the W and E sequences as well as sequences from many annual species. The H genomes sequences were in a clade with the F, P, and Ns genome sequences as sister groups. These two clades were more closely related to each other and to the L and Xp genomes than they were to the St genome sequences. These data support the hypothesis that the Y genome evolved in a diploid species and has a different origin from the St genome. PMID- 20363343 TI - Phylogenetic relationships of Sonoran Desert cactus beetles in the tribe Hololeptini (Coleoptera: Histeridae: Histerinae), with comments on the taxonomic status of Iliotona beyeri. AB - Nucleotide sequences from 16S rRNA and cytochrome c oxidase subunit I (COI) were used to examine phylogenetic relationships and evolution of beetles from the tribe Hololeptini (Coleoptera: Histeridae: Histerinae) that inhabit necrotic tissue of columnar cacti in the Sonoran Desert. Phylogenetic and morphological analyses revealed the presence of seven separate lineages, three representing species in the genus Iliotona, including I. beyeri stat. nov., and four species belonging to the genus Hololepta (sensu lato). The possible roles of historical vicariance and host plant associations on the evolution of the Hololeptini from the Sonoran Desert are discussed. PMID- 20363344 TI - Molecular evidence of cryptic speciation in the "cosmopolitan" excavating sponge Cliona celata (Porifera, Clionaidae). AB - Over the past several decades molecular tools have shown an enormous potential to aid in the clarification of species boundaries in the marine realm, particularly in morphologically simple groups. In this paper we report a case of cryptic speciation in an allegedly cosmopolitan and ecologically important species-the excavating sponge Cliona celata (Clionaidae, Hadromerida). In the Northeast Atlantic and Mediterranean C. celata displays a discontinuous distribution of its putative growth stages (boring, encrusting, and massive) leading us to investigate its specific status. Phylogenetic reconstructions of mitochondrial (COI, Atp8) and nuclear (28S) gene fragments revealed levels of genetic diversity and divergence compatible with interspecific relationships. We therefore demonstrate C. celata as constituting a species complex comprised of at least four morphologically indistinct species, each showing a far more restricted distribution: two species on the Atlantic European coasts and two on the Mediterranean and adjacent Atlantic coasts (Macaronesian islands). Our results provide further confirmation that the different morphotypes do indeed constitute either growth stages or ecologically adapted phenotypes as boring and massive forms were found in two of the four uncovered species. We additionally provide an overview of the cases of cryptic speciation which have been reported to date within the Porifera, and highlight how taxonomic crypsis may confound scientific interpretation and hamper biotechnological advancement. Our work together with previous studies suggests that overconservative systematic traditions but also morphological stasis have led to genetic complexity going undetected and that a DNA-assisted taxonomy may play a key role in uncovering the hidden diversity in this taxonomic group. PMID- 20363345 TI - A multi-locus phylogeny of Nectogalini shrews and influences of the paleoclimate on speciation and evolution. AB - Nectogaline shrews are a major component of the small mammalian fauna of Europe and Asia, and are notable for their diverse ecology, including utilization of aquatic habitats. So far, molecular phylogenetic analyses including nectogaline species have been unable to infer a well-resolved, well-supported phylogeny, thus limiting the power of comparative evolutionary and ecological analyses of the group. Here, we employ Bayesian phylogenetic analyses of eight mitochondrial and three nuclear genes to infer the phylogenetic relationships of nectogaline shrews. We subsequently use this phylogeny to assess the genetic diversity within the genus Episoriculus, and determine whether adaptation to aquatic habitats evolved independently multiple times. Moreover, we both analyze the fossil record and employ Bayesian relaxed clock divergence dating analyses of DNA to assess the impact of historical global climate change on the biogeography of Nectogalini. We infer strong support for the polyphyly of the genus Episoriculus. We also find strong evidence that the ability to heavily utilize aquatic habitats evolved independently in both Neomys and Chimarrogale+Nectogale lineages. Our Bayesian molecular divergence analysis suggests that the early history of Nectogalini is characterized by a rapid radiation at the Miocene/Pliocene boundary, thus potentially explaining the lack of resolution at the base of the tree. Finally, we find evidence that nectogalines once inhabited northern latitudes, but the global cooling and desiccating events at the Miocene/Pliocene and Pliocene/Pleistocene boundaries and Pleistocene glaciation resulted in the migration of most Nectogalini lineages to their present day southern distribution. PMID- 20363346 TI - Monophyly, phylogenetic position and the role of hybridization in Schoenoxiphium Nees (Cariceae, Cyperaceae). AB - Incongruence between gene trees, even within genomes, is often the result of hybridization and/or other processes such as incomplete lineage sorting, and can cause problems for phylogenetic analyses. We show here that the radiation of the Cyperaceae genus Schoenoxiphium involved at least one hybridization event with a closely related species of Carex, as indicated by a recombinant nuclear ITS region shared by all species in the S. rufum clade and C. camptoglochin. Recombinant sequences were confirmed with cloning experiments and recombination analyses. The monophyly of Schoenoxiphium has, in previous analyses, been suspected but not sufficiently supported, possibly due in part to this problem. Our phylogenetic analyses include an appropriate representation of Schoenoxiphium and other related Cariceae species and an extended sampling of the nuclear ITS and plastid marker regions, trnLF and rps16. We demonstrate that Schoenoxiphium is monophyletic, nested within Carex, and that several supported clades exist in Schoenoxiphium. PMID- 20363347 TI - Congruence between nuclear and mitochondrial DNA: combination of multiple nuclear introns resolves a well-supported phylogeny of New World orioles (Icterus). AB - Darwin's vision of a "Tree of Life" showing evolutionary relationships among all extant species seems an increasingly feasible goal, at least for vertebrate animals. However, virtually all published molecular phylogenies for closely related animals are based on a single locus - maternally inherited mitochondrial DNA. New approaches using multiple nuclear loci are needed to test published trees and better resolve the twigs of the entire tree of life. Here we use New World orioles (Icterus) to test an approach based on combined analysis of six independent Z chromosome introns. Combined analysis of multiple introns using traditional phylogenetic methods resolved a well-supported species phylogeny of New World orioles. In fact, all major lineages of orioles and several sub-clades that are well-supported by previously published mtDNA data are also strongly supported by the combined nuclear Z-intron tree. The male-biased Z-intron tree presented here is overwhelmingly congruent with the female-exclusive mtDNA tree. A slow rate of mutation relative to mtDNA resulted in generally poorly resolved gene trees when intron loci were analyzed separately. However, strong phylogenetic signal for all but the most recent divergences emerged once multiple loci were concatenated and analyzed in combination. Although there clearly are conditions under which concatenation analysis of nuclear DNA can be misleading, the congruence between mitochondrial and nuclear estimates of the Icterus phylogeny suggests that concatenation remains a powerful tool for inferring phylogenetic relationships for all but very recent divergences. PMID- 20363349 TI - Metabolic responses of Parastacus defossus and Parastacus brasiliensis (Crustacea, Decapoda, Parastacidae) to hypoxia. AB - The metabolic responses of two crayfish species living in different habitats, Parastacusdefossus and Parastacus brasiliensis, were analyzed after different periods of hypoxia (2.0mg O(2)/L of oxygen). In the laboratory, groups of animals were subjected to hypoxia for 1, 2, 4, and 8h. The hemolymph, hepatopancreas, muscle, and anterior and posterior gills were removed for determination of glucose, free glucose, glycogen, lactate, total proteins, total lipids, total cholesterol, arginine, and arginine phosphate. In both species, glucose and lactate increased significantly after 4h of hypoxia, but decreased after 8h (p>0.05) from the beginning of the experiment. Reductions of glycogen, lipids, and cholesterol were recorded in hepatopancreas and muscle tissue, especially of P. defossus, after 4h of hypoxia. Free glucose levels decreased in all tissues of P. brasiliensis, mainly in the hepatopancreas and muscle (p<0.05), while P. defossus showed smaller reductions of these reserves. All reserves in the anterior and posterior gills, with exception of the glycogen reserves, behaved similarly in both species. Both crayfishes stored and used arginine phosphate, mainly P. defossus, which also showed higher concentrations of all metabolites than did P. brasiliensis. Both species showed metabolic adaptations to hypoxia, but, as expected, P. defossus appeared to be better adapted. PMID- 20363348 TI - Metabolic manipulation of glycosylation disorders in humans and animal models. AB - In the last decade, over 40 inherited human glycosylation disorders were identified. Most patients have hypomorphic, rather than null alleles. The phenotypic spectrum is broad and most of the disorders affect embryonic and early post-natal development; a few appear in adult life. Some deficiencies can be treated with simple dietary sugar (monosaccharide) supplements. Here we focus on four glycosylation disorders that have been treated with supplements in patients or in model systems, primarily the mouse. Surprisingly, small differences in the amount of exogenous sugar have a major impact on the diseases in specific cells or organs while others are unaffected. The underlying mechanisms are mostly unknown, but changes in the contributions of the de novo, salvage and dietary pathways may contribute to the beneficial outcome. Clearly, the metabolic chart is not flat; all arrows are not equally robust at all points of time and space. This metabolic perspective may help explain some of these observations and guide the development of other vertebrate models of glycosylation disorders that can respond to dietary manipulation. PMID- 20363350 TI - Retention of fluid and particles in captive tapirs (Tapirus sp.). AB - The retention of ingesta in the digestive tract is a major characteristic of herbivorous animals. We measured particle and fluid mean retention times (MRT) in 13 lowland tapirs (Tapirus terrestris) and 5 Malayan tapirs (Tapirus indicus) from five zoological institutions on their usual zoo diet and 2 lowland and 4 Malayan tapirs additionally on roughage-only diets (total n of trials=24) with cobalt-EDTA as fluid and chromium-mordanted fibre (<2 mm) as particle markers. MRT for fluid and particles averaged 42+/-16 h and 55+/-18 h in lowland and 40+/ 13 h and 56+/-14 h in Malayan tapirs. In a General Linear Model, neither Tapir species, body mass or diet (characterised by the proportion of roughage) was significantly related to MRT, but dry matter intake was, with a steep decline in MRT with higher intake levels. Compared to other hindgut fermenters, tapirs have a low defecation frequency, which might be linked to their comparatively low food intake. Their gastrointestinal capacity (in dry matter: 1.63+/-0.63% of body mass) is similar to that calculated for horses. A comparison of the difference in fluid and particle MRT in large hindgut fermenters (horses, rhinoceroses, elephants, and the tapirs of this study) shows that longer absolute particle MRT are linked to shorter relative fluid MRT, possibly indicating a more thorough 'washing' of particulate ingesta with digestive fluids at longer particle MRT. The only outlier to this general pattern, with an exceptionally high difference between fluid and particle MRT, indicating a particularly efficient ingesta washing, is the white rhinoceros (Ceratotherium simum). If possible, results of this study should be compared to findings in tapirs on natural diets. PMID- 20363351 TI - Baroreflex control of heart rate in the broad-nosed caiman Caiman latirostris is temperature dependent. AB - It has been suggested that ectothermic vertebrates primarily control blood pressure to protect the pulmonary vasculature from oedema caused by high pressure, while endothermic vertebrates control blood pressure to maintain adequate oxygen delivery to the tissues. In the present study we have characterised how temperature affects the cardiac limb of the baroreflex in the intact unanaesthetized broad-nosed caiman (Caiman latirostris) by pharmacological manipulation of blood pressure in a "closed-loop" system. Sodium nitroprusside (SNP) and phenylephrine were used to manipulate arterial pressure and the resulting alterations in heart rate were used to calculate the gain of the baroreflex. Both drugs were infused as bolus injections in concentrations of 5, 10, 25, 50 and 100 microg kg(-1). The barostatic response was present at both 15 and 30 degrees C, and, at both temperatures, C.latirostris responded to reductions in systemic blood pressure (Psys). At 30 degrees C the baroreflex was more pronounced at a blood pressure lower than control value (52.3 cmH(2)O) with a maximal baroreflex gain of 1.97 beats min(-)(1)cmH(2)O(-1) at a Psys of 41.9 cmH(2)O, and therefore seems to counteract hypotension. In contrast, the maximal baroreflex at 15 degrees C was found at a Psys almost equal to the control value. The highest baroreflex gain in response to change in blood pressure was measured at the highest temperature. Thus, C.latirostris exhibit a temperature dependent barostatic response. PMID- 20363352 TI - Cardiovascular and respiratory developmental plasticity under oxygen depleted environment and in genetically hypoxic zebrafish (Danio rerio). AB - Known vertebrate response to low oxygen concentration include change in carbohydrate metabolism, increase in nitric oxide, stimulation of red blood cell and hemoglobin production and induction of gene expression for glycolytic enzymes and hormones. Also, extreme hypoxia plays main role in pathological studies of cardiac dysfunction. The morphological and physiological developmental studies of the cardiovascular system under low oxygen are important as it is directly related to oxygen supply and consumption. Furthermore, cardiac function demands high energy during system development and thus it is most likely to be affected by hypoxia. Zebrafish (Danio rerio) can act as a model organism for oxygen demand management study as in natural environment, due to ecological disturbances, it is exposed to changes in oxygen concentrations routinely and thus would have natural ability to cope with it for survival. We have studied, in zebrafish, i) cardiovascular flexibility under extreme hypoxia (PO(2)=20 Torr, 3 kPa) at 3-10 dpf (days post-fertilization), ii) cardiac re-animation in normoxia (PO(2)=152 Torr, 20 kPa) after 90 min of anoxia (PO(2)=0 Torr, 0 kPa)-induced suspended animation at 4 dpf and iii) oxygen consumption in 8 dpf von Hippel-Lindau (vhl( )(/)(-)) mutant that exhibits an artificial hypoxic response under normoxic conditions. In hypoxic fish, cardiac output, stroke volume and end-diastolic volume were elevated while intersegmental blood vessels vascularization index at 6 dpf and at 10 dpf was 22% and 11% higher respectively as compared to the normoxic fish. The heart rate in hypoxic fish was lower until 6 dpf and then showed an elevated trend. There was no significant difference in body length between the hypoxic and normoxic individuals. The observed changes may have enhanced the performance of the cardiovascular system for oxygen uptake. We also report for the first time that the post-anoxia re-animated heart rate returns to normal after 48h. Measurement of oxygen consumption in 8 dpf hyperventilating vhl(-)(/)(-) mutant was, unexpectedly, significantly lower than the non-mutant fish of the same age which point towards artificial hypoxic signal from brain in these mutants. PMID- 20363353 TI - Pulmonary artery pressure responses to increased cardiac output in chickens with raised metabolic rate. AB - Previous work has shown remarkable differences in the pressure-flow relations of the pulmonary circulation between birds and mammals. For example several studies suggest that the avian pulmonary blood vessels behave like rigid tubes, very different from the situation in mammalian lung. We therefore speculated that birds would develop high pulmonary artery pressures when the cardiac output was substantially increased during heavy exercise, for example during flight. However because of the technical difficulties of measuring pulmonary artery pressures in flight, the metabolic rate and cardiac output in anesthetized chickens were increased by infusing 2,4 Dinitrophenol (DNP) and the mean pressure was measured by means of a catheter in the pulmonary artery. Although the pulmonary artery pressure rose steadily as cardiac output increased, it remained below the high levels predicted from the previous studies for similar changes in pulmonary blood flow. Furthermore the increase in pressure was less than in mammals where recruitment and distension of pulmonary capillaries are known to occur. The reasons for this unexpected result are not clear. PMID- 20363354 TI - Sexually dimorphic expression of dmrt1 in immature and mature Atlantic cod (Gadus morhua L.). AB - The Doublesex and Mab-3 related transcription factor 1 (Dmrt1) is implicated in testis development in a variety of vertebrates, including teleost fish. Atlantic cod (Gadusmorhua L.) is a promising cold-water aquaculture species, but early sexual maturation of males in particular is a major problem in today's cod farming. Molecular studies of dmrt1 were initiated to gain knowledge about the regulation of gonad development for the first time in a species of the superorder Paracanthopterygii. The predicted cod Dmrt1 of 310 amino acids contains a highly conserved DM domain, including six Cys residues probably involved in the formation of a double zinc-finger motif for DNA binding. The tissue expression analysis revealed that dmrt1 is expressed exclusively in the gonads, and the signal was localized in the germ cells in both genders by in situ hybridization. Sexually dimorphic expression of dmrt1 was documented by quantitative PCR with the highest mRNA levels in immature males corresponding to the start of spermatogenesis. Although significantly less expressed in the ovary, Dmrt1 might also play a role in oogenesis. Southern blot analysis revealed several DM domain containing genes in the cod genome, but no sex-linked polymorphism was shown. PMID- 20363355 TI - Regulation of FADS2 expression and activity in European sea bass (Dicentrarchus labrax, L.) fed a vegetable diet. AB - Supplies of marine fish oils are limited, and continued growth in aquaculture production dictates that lipid substitutes in fish diets must be used without compromising fish health and product quality. In this study, the total substitution of a fish meal and fish oil by a blend of vegetable meals (corn, soybean, wheat and lupin) and linseed oil in the diet of European sea bass (Dicentrachus labrax) was investigated. Two groups of European sea bass were fed with fish diet (FD) or vegetable diet (VD) for 9months. VD, totally deprived of eicosapentaenoate (EPA; 20:5n-3) and docosahexaenoate (DHA; 22:6n-3), revealed a nutritional deficiency and affected growth performance. Whilst VD induced a significant increase in fatty acid desaturase 2 (FADS2) and sterol binding regulatory element-binding protein 1 (SREBP-1) mRNA levels, the desaturation rate of [1-(14)C]18:3n-3 into [1-(14)C]18:4n-3, analysed in microsomal preparations using HPLC method, did not show an upregulation of FADS2 activities in liver and intestine of fish fed VD. Moreover Western-blot analysis did not revealed any significant difference of FADS2 protein amount between the two dietary groups. These data demonstrate that sea bass exhibits a desaturase (FADS2) activity whatever their diet, but a post-transcriptional regulation of fads2 RNA prevents an increase of enzyme in fish fed a HUFA-free diet. This led to a lower fish growth and poor muscle HUFA content. PMID- 20363356 TI - Highly sulfated dermatan sulfate from the skin of the ray Raja montagui: anticoagulant activity and mechanism of action. AB - The dermatan sulfate (DS) isolated from the ray skin Raja montagui was identified and characterized. Its average molecular weight (Mw) and sulfate content were 39 kDa and 25% w/w, respectively. This DS prolonged thrombin time and activated partial thromboplastin time and inhibited the thrombin generation in a concentration-dependent manner whereas it had no effect on the anti-Xa assay and on platelet function. Data from the anti-IIa assay allowed the assessment of the specific anticoagulant activity which was 40 units/mg. The kinetics of the thrombin inhibition by heparin cofactor II (HCII) has been studied as a function of DS concentration according to a kinetic model in which the polysaccharide binds quickly to the inhibitor and forms a complex more reactive than the free inhibitor towards thrombin. This DS accelerated thrombin inhibition exclusively by HCII. The dissociation constant of the DS-HCII complex, K(DSHCII), and the rate constant of the thrombin inhibition by this complex, k, were (2.93+/ 0.25)x10(-6)M and (2.2+/-0.35)x10(9)M(-1)min(-1), respectively. Our findings indicated that the major polysaccharide in the skin of the ray Raja montagui was a DS endowed with a high anticoagulant effect mediated by HCII and which may constitute an anticoagulant drug of interest in anticoagulant therapy. PMID- 20363358 TI - TLR2 signalling: At the crossroads of commensalism, invasive infections and toxic shock syndrome by Staphylococcus aureus. AB - Although up to 60% of the population at any one time carry Staphylococcus aureus (S. aureus) without significant clinical consequences, infections by S. aureus are a major health care threat in the Western world. The underlying mechanisms that determine this two-sided interaction between S. aureus and the human immune system are unknown. Work on the pathogenesis of S. aureus infections and toxic shock syndrome may provide unexpected clues to understand the duality of such an interaction. Recent evidence suggests that the cell wall of S. aureus contains peptidoglycan-embedded TLR2 ligands that not only act as pathogen-associated molecular patterns, which trigger pro-inflammatory innate immune responses, but also can act as anti-inflammatory modulators of the pathogenicity by this microbe and its toxins. Here, we discuss this theme in the context of staphylococcal toxic shock syndrome and explore its implications on the development of therapeutic strategies to prevent and treat S. aureus infections. PMID- 20363357 TI - Molecular signatures and biological pathway profiles of human corneal epithelial progenitor cells. AB - Identification and isolation of adult stem cells are still challenging for stem cell biologists. For example, no consensus exists yet regarding definitive markers for corneal epithelial stem cells, which have been identified to reside in the limbus for two decades. This study characterized the molecular signatures and biological pathways of limbal epithelial progenitors, the rapid adherent cells (RAC) isolated by adhesion on collagen IV, using human genome microarrays, real-time PCR and immunofluorescent staining. The microarrays produced highly reproducible data not only for all gene transcripts, but also for significantly changed genes, although the total 12 samples of 3 cell populations in 2 arrays were isolated from 4 separate experiments at different time period. The hierarchical clustering heatmap visually revealed that RAC progenitor population displayed distinguishably characteristic gene expression profile. With verification of 27 important genes by quantitative real-time PCR, the microarray data not only confirm the expression patterns of 15 known genes as stem cell associated markers representing limbal stem cell phenotype, but also identified many significantly regulated genes expressed by limbal progenitor cells. Transcription factor TCF4 and cell surface protein SPRRs were identified as potentially positive or negative markers, respectively, for corneal epithelial progenitor cells. Using GenMAPP and MAPPFinder, we have identified three patterns of biological pathway profiles, overexpressed, underexpressed and balanced, by RAC progenitors based on gene ontology categories. These genes and related pathways are interesting targets for further identification and isolation of limbal stem cells as well as other tissue-specific adult stem cells. PMID- 20363359 TI - The therapeutic prospects of using L-carnitine to manage hypertension-related organ damage. AB - Subclinical organ damage is a very important aspect when assessing total cardiovascular risk in hypertensive subjects. Therapeutic strategies in those patients should consider treatment of hypertension-related cardiovascular and renal damage in addition to achieving the recommended blood pressure targets. l carnitine (LC) is a naturally occurring compound that is administered exogenously for treatment of patients that are deficient in carnitine. The currently available data do not support a preferential role of LC as an antihypertensive agent compared to other available drugs. However, its ability to simultaneously modulate several targets and/or pathways provides antioxidant and anti inflammatory properties. These additional properties might justify the therapeutic use of LC as a protective agent against cardiovascular and renal remodelling in arterial hypertension. PMID- 20363360 TI - Big nation, nano dream - the prospects of India's nanotech revolution. PMID- 20363361 TI - Mutagenicity of N-ethyl-N-nitrosourea, N-methyl-N-nitrosourea, methyl methanesulfonate and ethyl methanesulfonate in the developing Syrian hamster fetus. AB - N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) are well-known direct-acting transplacental mutagens and carcinogens. Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) are also direct-acting but more stable compounds and form a different proportion of the various methyl and ethyl DNA adducts. The transplacental mutagenicity and carcinogenicity of MMS and EMS have not been well characterized. We tested the mutagenicity to the developing Syrian hamster by these compounds under identical conditions and with a range of dose. Mutant fetal cells were selected for diphtheria toxin resistance. All four compounds were significantly mutagenic. MNU was the most active and MMS the least active of the compounds. ENU and MNU demonstrated linear dose-response curves, whereas that for EMS seemed to be supralinear over the range 0.125-0.5 mmol/kg. At its highest dose, EMS was comparable to ENU in mutagenicity. In view of a recent accidental exposure of pregnant women and others to EMS, further studies of this compound in animal models may be warranted. PMID- 20363362 TI - Blastocystis sp. subtype 2 detection during recurrence of gastrointestinal and urticarial symptoms. AB - Blastocystis is a common unicellular intestinal parasite in humans. Its clinical relevance is still subject to discussion with numerous conflicting reports on its ability to cause disease. A remarkable genetic heterogeneity among isolates suggests an association between distinct subtypes (STs) and pathogenicity, although a clear correlation between symptoms and subtype is lacking. Here, we report on a clinical case which possibly links Blastocystis sp. ST2 infection with the simultaneous occurrence of gastrointestinal illness and generalized chronic urticaria. Despite repeated chemotherapy with different antimicrobial drugs, both the gastrointestinal and cutaneous disorders reoccurred after short symptom-free intervals. Eradication of the parasite and permanent resolution of the patient's medical condition was finally achieved with the combined application of metronidazole and paromomycin. PMID- 20363363 TI - NO modulates the molecular basis of rat interscapular brown adipose tissue thermogenesis. AB - Molecular mechanisms underlying interscapular brown adipose tissue (IBAT) thermogenesis were elucidated. Namely, gene and/or protein expression of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARgamma), PPARgamma-coactivator-1alpha (PGC-1alpha), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) - key molecules that regulate thermogenesis-related processes - mitochondriogenesis, angiogenesis and IBAT hyperplasia, in rats subjected to cold (4+/-1 degrees C) for 1, 3, 7, 12, 21 and 45days were investigated. Particularly, to examine influence of nitric oxide (NO) on IBAT thermogenic-program, cold-exposed animals were treated by l-arginine or N(omega)-nitro-l-arginine-methyl ester (L-NAME). Related to control (22+/-1 degrees C), cold induced time-coordinated UCP1, PPARgamma and PGC-1alpha transcriptional activation accompanied by PCNA activation and increased VEGF immunolabeling that correlate with endothelial NO synthase (eNOS) transcriptional activation suggesting NO involvement in these thermogenic-factors activation. Observed molecular changes were translated into increased mitochondrial-remodeling, angiogenesis, and IBAT hyperplasia. l Arginine augmented and prolonged cold-induced increase of eNOS, inducible NOS and thermogenic-molecules expression, IBAT nerve supply, vascularity, hyperplasia and mitochondrial-remodeling, while L-NAME had an opposite effects. Results show that NO improves thermogenesis-related mitochondriogenesis, angiogenesis and tissue hyperplasia, positively affecting molecular basis of these processes, suggesting that NO is an essential regulator of IBAT thermogenic-program operating, at genes, proteins and tissue structure levels. PMID- 20363364 TI - A set of ontologies to drive tools for the control of vector-borne diseases. AB - We are developing a set of ontologies dealing with vector-borne diseases as well as the arthropod vectors that transmit them. After building ontologies for mosquito and tick anatomy we continued this project with an ontology of insecticide resistance followed by a series of ontologies that describe malaria as well as physiological processes of mosquitoes that are relevant to, and involved in, disease transmission. These will later be expanded to encompass other vector-borne diseases as well as non-mosquito vectors. The aim of the whole undertaking, which is worked out in the frame of the international IDO (Infectious Disease Ontology) project, is to provide the community with a set of ontological tools that can be used both in the development of specific databases and, most importantly, in the construction of decision support systems (DSS) to control these diseases. PMID- 20363365 TI - The utility of general purpose versus specialty clinical databases for research: warfarin dose estimation from extracted clinical variables. AB - There is debate about the utility of clinical data warehouses for research. Using a clinical warfarin dosing algorithm derived from research-quality data, we evaluated the data quality of both a general-purpose database and a coagulation specific database. We evaluated the functional utility of these repositories by using data extracted from them to predict warfarin dose. We reasoned that high quality clinical data would predict doses nearly as accurately as research data, while poor-quality clinical data would predict doses less accurately. We evaluated the Mean Absolute Error (MAE) in predicted weekly dose as a metric of data quality. The MAE was comparable between the clinical gold standard (10.1mg/wk) and the specialty database (10.4 mg/wk), but the MAE for the clinical warehouse was 40% greater (14.1mg/wk). Our results indicate that the research utility of clinical data collected in focused clinical settings is greater than that of data collected during general-purpose clinical care. PMID- 20363367 TI - A 41-year-old woman with abdominal complaints: is it food allergy or food intolerance? How to tell the difference. PMID- 20363366 TI - Reinduction with certolizumab pegol in patients with relapsed Crohn's disease: results from the PRECiSE 4 Study. AB - BACKGROUND & AIMS: We sought to determine the efficacy of certolizumab pegol reinduction in patients with active Crohn's disease who respond to induction therapy with certolizumab pegol and then relapse during continuous or interrupted maintenance therapy. METHODS: In the Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial, 428 patients who responded to induction therapy with certolizumab pegol at week 6 were randomized to continuous therapy with certolizumab pegol or placebo (drug interruption) during weeks 6 to 26. Patients who relapsed before week 26 could enter PRECiSE 4, an ongoing open-label extension trial in which patients on continuous therapy underwent recapture with a single extra 400-mg dose of certolizumab pegol, and patients who relapsed after drug interruption underwent reinduction with certolizumab pegol 400 mg at weeks 0, 2, and 4 followed by maintenance with certolizumab pegol 400 mg every 4 weeks. Disease activity was measured by the Harvey-Bradshaw Index. RESULTS: During PRECiSE 2, 124 patients had disease relapse and entered PRECiSE 4; 49 patients had received continuous therapy and 75 patients had drug interruption. At week 4 of PRECiSE 4, response rates were 63% in patients who relapsed on continuous therapy and 65% after drug interruption. Response was maintained in 55% and 59% of these responders, respectively, through week 52. CONCLUSIONS: Administration of 1 additional dose of certolizumab pegol to patients who relapsed on continuous maintenance therapy, and certolizumab pegol reinduction to those who relapsed after drug interruption, are effective strategies for treating patients who have relapsed after successful induction therapy with certolizumab pegol. PMID- 20363369 TI - A case of cholestatic jaundice: amyloidosis. PMID- 20363370 TI - Electronic images of the month. Twisting and infarction of the entire greater omentum. PMID- 20363368 TI - Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease. AB - BACKGROUND & AIMS: The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. METHODS: We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. RESULTS: Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). CONCLUSIONS: Patients with early and late adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. PMID- 20363371 TI - Detective work in drug-induced liver injury: sometimes it is all about interviewing the right witness. AB - Diagnosing drug-induced liver injury (DILI) relies primarily on history taking. We report 4 cases in which DILI was missed or the drug was misidentified when physicians relied solely on patient history. We reviewed 27 cases referred with possible DILI from August 1, 2009, to February 1, 2010. Four patients seemed to be reliable historians, but their cases were greatly clarified by a call to their pharmacist. One subject, who forgot a new medication, underwent an unfruitful evaluation including surgery. Another patient had acetaminophen toxicity that was missed because she grossly underreported her pain medication use. The third and fourth patients forgot taking amoxicillin/clavulanate, so other agents mistakenly were implicated. Roussel Uclaf Causality Assessment Method scores were 8 (probable) or 9 (highly probable) for all 4 cases. Without pharmacy input, DILI was missed in 2 cases and the wrong agent was implicated twice. Reviewing pharmacy records can be crucial for patients and DILI research. We recommend calling the pharmacist directly for increased liver enzyme levels of unclear source or suspected DILI regardless of patient history. PMID- 20363372 TI - Image of the month. Primary malignant melanoma of the esophagus. PMID- 20363373 TI - Polycystic echinococcosis. PMID- 20363374 TI - Functional associations of similar MHC alleles and shared parasite species in two sympatric lemurs. AB - Several recent studies of animals in their natural surroundings found evidence for effects of certain major histocompatibility complex (MHC) immune gene alleles on the parasite load. However, in multi-infected individuals the particular selection pressure exerted by specific parasites has rarely been explored. In this study we took advantage of the parasitological and genetic data of two previously investigated Malagasy lemur species (Cheirogaleus medius and Microcebus murinus). We investigated whether the two sympatric and ecologically similar primates are infected by similar parasite species and explored if certain parasites are associated with particular MHC alleles. Our study revealed that most of the parasite egg morphotypes were found in both hosts. In each lemur species we identified one MHC allele which was positively associated with Ascaris infection. Interestingly, these MHC alleles were very similar to each other but differed from all other investigated MHC alleles in an amino acid substitution in a putative functional important antigen binding site. Thus, our study gives first intriguing evidence for a direct connection between certain antigen binding sites of MHC molecules with a particular parasite in two wild primate populations. This may indicate that indeed certain parasites exert direct selective pressure on the MHC of wild living hosts. PMID- 20363375 TI - Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp. AB - Assessing how natural selection, negative or positive, operates on genes with low polymorphism is challenging. We investigated the genetic diversity of orthologous genes encoding the rhoptry-associated protein 1 (RAP-1), a low polymorphic protein of malarial parasites that is involved in erythrocyte invasion. We applied evolutionary genetic methods to study the polymorphism in RAP-1 from Plasmodium falciparum (n=32) and Plasmodium vivax (n=6), the two parasites responsible for most human malaria morbidity and mortality, as well as RAP-1 orthologous in closely related malarial species found in non-human primates (NHPs). Overall, genes encoding RAP-1 are highly conserved in all Plasmodium spp. included in this investigation. We found no evidence for natural selection, positive or negative, acting on the gene encoding RAP-1 in P. falciparum or P. vivax. However, we found evidence that the orthologous genes in non-human primate parasites (Plasmodium cynomolgi, Plasmodium inui, and Plasmodium knowlesi) are under purifying (negative) selection. We discuss the importance of considering negative selection while studying genes encoding proteins with low polymorphism and how selective pressures may differ among orthologous genes in closely related malarial parasites species. PMID- 20363376 TI - Sequence variation of ookinete surface proteins Pvs25 and Pvs28 of Plasmodium vivax isolates from Southern Mexico and their association to local anophelines infectivity. AB - The polymorphism of Pvs25 and Pvs28 ookinete surface proteins, their association to circumsporozoite protein repeat (CSPr) genotypes (Vk210 and Vk247) and their infectivity to local Anopheles albimanus and Anopheles pseudopunctipennis were investigated in Plasmodium vivax-infected blood samples obtained from patients in Southern Mexico. The pvs25 and pvs28 complete genes were amplified, cloned and sequenced; and the CSPr genotype was determined by PCR amplification and hybridization. The amino acid Pvs25 and Pvs28 polymorphisms were mapped to their corresponding protein structure. Infected blood samples were simultaneously provided through artificial feeders to both mosquito species; the ratio of infected mosquitoes and oocyst numbers were recorded. The polymorphism of pvs25 and pvs28 was limited to few nucleotide positions, and produced three haplotypes: type A/A parasites presented Pvs25 and Pvs28 amino acid sequences identical to that of Sal I reference strain; parasites type B1 presented a mutation 130 Ile- >Thr in Pvs25, while type B2 presented 87 Gln-->Lys/130 Ile-->Thr in the same molecule. Both types B1 and B2 parasites presented changes in Pvs28 at 87 Asn- >Asp, 110 Tyr-->Asn and five GSGGE/D repeat sequences between the fourth EGF-like domain and the GPI. Most P. vivaxparasites from the coastal plains and the overlapping region were Pvs25/28 A/A, CSPrVk210 and were infective only to An. albimanus (p< or =0.0001). Parasites originating in foothills were Pvs25/28 type B1/B or B2/B and CSPrVk210 or Vk247, and were more infective to An. pseudopunctipennis than to An. albimanus (p< or =0.001). These results and the analysis of Pvs25/28 from other parts of the world indicated that non-synonymous variations in these proteins occur in amino acid residues exposed on the surface of the proteins, and are likely to interact with midgut mosquito ligands. We hypothesize that these molecules have been shaped by co-evolutionary adaptations of parasites to their susceptible vectors. PMID- 20363377 TI - Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation. AB - Familial recurrence of atrial fibrillation (AF) is reported in up to 15% of patients with lone AF. Recently, it was proposed that congenital defects in the morphogenesis of the pulmonary vein myocardium are involved in genetic pathogenesis of lone AF. GATA4 is a cardiac transcription factor essentially involved in myocardial development. Mutations in GATA4 are associated with congenital cardiac malformations. To investigate whether GATA4 mutations represent a genetic origin for AF the coding region of GATA4 was sequenced in 96 patients with lone AF. We found a GATA4 mutation (M247T) in a patient with familial lone AF and atrial septal aneurysm without interatrial shunts. The mutation affects a deeply conserved domain adjacent to the first zinc finger domain of GATA4 and was not reported before. A second GATA4 mutation (A411V) was found in a female patient with sporadic lone AF. This variant was previously reported in patients with cardiac septal defects. However, no anomalies of the atrial or ventricular septa were noted in the AF patient harboring A411V. We report for the first time that mutations in the cardiac transcription factor GATA4 may represent a genetic origin of lone AF. The study proposes that lone AF may share a common genetic origin with congenital cardiac malformations. PMID- 20363392 TI - Determination of iron in seawater by electrothermal atomic absorption spectrometry and atomic fluorescence spectrometry: a comparative study. AB - Two methods available for direct determination of total Fe in seawater at low concentration level have been examined: electrothermal atomization atomic absorption spectrometry (ETAAS) and electrothermal atomization laser excited atomic fluorescence spectrometry (ETA-LEAFS). In a first part, we have optimized experimental conditions of ETAAS (electrothermal program, matrix chemical modification) for the determination of Fe in seawater by minimizing the chemical interference effects and the magnitude of the simultaneous background absorption signal. By using the best experimental conditions, a detection limit of 80 ng L( 1) (20 microL, 3sigma) for total Fe concentration was obtained by ETAAS. Using similar experimental conditions (electrothermal program, chemical modification), we have optimized experimental conditions for the determination of Fe by LEAFS. The selected experimental conditions for ETA-LEAFS: excitation wavelength (296.69 nm), noise attenuation and adequate background correction led to a detection limit (3sigma) of 3 ng L(-1) (i.e. 54 pM) for total Fe concentration with the use a 20 microL seawater sample. For the two methods, concentration values obtained for the analysis of Fe in a NASS-5 (0.2 microg L(-1)) seawater sample were in good agreement with the certified values. PMID- 20363393 TI - Classification of cultivated mussels from Galicia (northwest Spain) with European Protected Designation of Origin using trace element fingerprint and chemometric analysis. AB - Inductively coupled plasma-mass spectrometry (ICP-MS) in combination with different supervised chemometric approaches has been used to classify cultivated mussels in Galicia (Northwest of Spain) under the European Protected Designation of Origin (PDO). 158 mussel samples, collected in the five rias on the basis of the production, along with minor and trace elements, including high field strength elements (HFSEs) and rare earth elements (REEs), were used with this aim. The classification of samples was achieved according to their origin: Galician vs. other regions (from Tarragona, Spain, and Ethang de Thau, France) and between the Galician Rias. The ability of linear discriminant analysis (LDA), soft independent modelling of class analogy (SIMCA) and artificial neural network (ANN) to classify the samples was investigated. Correct assignations for Galician and non-Galician samples were obtained when LDA and SIMCA were used. ANNs were more effective when a classification according to the ria of origin was to be applied. PMID- 20363391 TI - Multi-dimensional liquid chromatography in proteomics--a review. AB - Proteomics is the large-scale study of proteins, particularly their expression, structures and functions. This still-emerging combination of technologies aims to describe and characterize all expressed proteins in a biological system. Because of upper limits on mass detection of mass spectrometers, proteins are usually digested into peptides and the peptides are then separated, identified and quantified from this complex enzymatic digest. The problem in digesting proteins first and then analyzing the peptide cleavage fragments by mass spectrometry is that huge numbers of peptides are generated that overwhelm direct mass spectral analyses. The objective in the liquid chromatography approach to proteomics is to fractionate peptide mixtures to enable and maximize identification and quantification of the component peptides by mass spectrometry. This review will focus on existing multidimensional liquid chromatographic (MDLC) platforms developed for proteomics and their application in combination with other techniques such as stable isotope labeling. We also provide some perspectives on likely future developments. PMID- 20363394 TI - Evaluation of the residual liquid junction potential contribution to the uncertainty in pH measurement: a case study on low ionic strength natural waters. AB - The residual liquid junction potential (RLJP) needs to be accounted for in pH uncertainty estimation. Attempts to do this and the currently available methods for evaluating the RLJP are critically discussed and their weak sides are pointed out. In this work an empirical approach to the problem is proposed. It is based on the use of the RLJP bias estimated on a variety of measurement conditions for a specific class of analytical objects essentially differing in ionic strength from the pH calibration buffers. The data from five independent studies, including interlaboratory comparisons, on pH measurement in low ionic strength waters were used to find the overall bias observed in the 10(-4) mol dm(-3) strong acid solution. The procedure includes quantifying the uncertainty of bias values from separate studies by combination of the relevant uncertainty components and testing the consistency of the data. The weighted mean bias in pH was found to be 0.043+/-0.007 (k=2). With this estimate, the pH measurement uncertainties calculated according to the previously suggested procedure (I. Leito, L. Strauss, E. Koort, V. Pihl, Accredit. Qual. Assur. 7 (2002) 242-249.) can be enlarged to take the uncorrected bias into account. The resulting uncertainties on the level of 0.10-0.14 (k=2) are obtained in this way for pH measurement in water and poorly buffered aqueous solutions in the range of pH 7.5 3.5. PMID- 20363395 TI - Significance of data treatment and experimental setup on the determination of copper complexing parameters by anodic stripping voltammetry. AB - Different procedures of voltammetric peak intensities determination, as well as various experimental setups were systematically tested on simulated and real experimental data in order to identify critical points in the determination of copper complexation parameters (ligand concentration and conditional stability constant) by anodic stripping voltammetry (ASV). Varieties of titration data sets (Cu(measured)vs. Cu(total)) were fitted by models encompassing discrete sites distribution of one-class and two-class of binding ligands (by PROSECE software). Examination of different procedures for peak intensities determination applied on voltammograms with known preset values revealed that tangent fit (TF) routine should be avoided, as for both simulated and experimental titration data it produced an additional class of strong ligand (actually not present). Peak intensities determination by fitting of the whole voltammogram was found to be the most appropriate, as it provided most reliable complexation parameters. Tests performed on real seawater samples under different experimental conditions revealed that in addition to importance of proper peak intensities determination, an accumulation time (control of the sensitivity) and an equilibration time needed for complete complexation of added copper during titration (control of complexation kinetics) are the keypoints to obtain reliable results free of artefacts. The consequence of overestimation and underestimation of complexing parameters is supported and illustrated by the example of free copper concentrations (the most bioavailable/toxic specie) calculated for all studied cases. Errors up to 80% of underestimation of free copper concentration and almost two orders of magnitude overestimation of conditional stability constant were registered for the simulated case with two ligands. PMID- 20363396 TI - Dissolved oxygen amperometric sensor based on layer-by-layer assembly using host guest supramolecular interactions. AB - The development of a simple, efficient and sensitive sensor for dissolved oxygen is proposed using the host-guest binding of a supramolecular complex at a host surface by combining a self-assembled monolayer (SAM) of mono-(6-deoxy-6 mercapto)-beta-cyclodextrin (betaCDSH), iron (III) tetra-(N-methyl-4-pyridyl) porphyrin (FeTMPyP) and cyclodextrin-functionalized gold nanoparticles (CDAuNP). The supramolecular modified electrode showed excellent catalytic activity for oxygen reduction. The reduction potential of oxygen was shifted about 200 mV toward less negative values with this modified electrode, presenting a peak current much higher than those observed on a bare gold electrode. Cyclic voltammetry and rotating disk electrode (RDE) experiments indicated that the oxygen reduction reaction involves probably 4-electrons with a rate constant (k(obs)) of 7 x 10(4) mol(-1) Ls(-1). A linear response range from 0.2 up to 6.5 mg L(-1), with a sensitivity of 5.5 microA L mg(-1) (or 77.5 microA cm(-2) L mg( 1)) and a detection limit of 0.02 mg L(-1) was obtained with this sensor. The repeatability of the proposed sensor, evaluated in terms of relative standard deviation was 3.0% for 10 measurements of a solution of 6.5 mg L(-1) oxygen. PMID- 20363397 TI - Application of a modified enzyme-linked immunosorbent assay for 3-amino-2 oxazolidinone residue in aquatic animals. AB - Furazolidone has been banned from use in food animals because of its carcinogenicity and mutagenicity, but its continued misuse is widespread in aquacultures. Therefore, there is an urgent need for a simple, reliable, and rapid method for the detection of its marker residue, 3-amino-2-oxazolidinone (AOZ), in aquatic products. In this regard, we modified a simplified indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) to address this need. A good linearity was achieved over a concentration range of 0.05-12.15 microg L( 1), and the IC(50) value was 0.96 microg L(-1). The sample preparation was simple and effective included water bath treatments, acid hydrolysis combined with overnight derivatization of AOZ by benzaldehyde. The limit of detection and the limit of quantification were 0.15 and 0.3 microg kg(-1). The recoveries of AOZ in all tissues were between 78.0-95.3% at the levels of 0.3, 1.0, and 2.0 microg kg( 1). The inter-assay variability was less than 19.1%. The modified ic-ELISA was applied in quantification of AOZ elimination in carp. The results showed that AOZ was quite difficult to eliminate. Good correlations of the results obtained by ELISA and LC-MS/MS were observed in incurred carp muscle (r=0.9923) and carp plasma (r=0.9915) at the levels of 2.5-571.8 microg kg(-1) (microg L(-1)). Better results were obtained by modified ic-ELISA when compared with commercial ELISA kit. Therefore, the present assay is considered a rapid, accurate, reliable, and inexpensive method for the detection of furazolidone-residues in the edible tissues of aquatic animals. PMID- 20363398 TI - Modeling of electrokinetic transport in silica nanofluidic channels. AB - We present a theoretical and numerical modeling study of the multiphysicochemical process in electrokinetic transport in silica nanochannels. The electrochemical boundary condition is solved by considering both the chemical equilibrium on solid-liquid interfaces and the salt concentration enrichment caused by the double layer interaction. The transport behavior is modeled numerically by solving the governing equations using the lattice Poisson-Boltzmann method. The framework is validated by good agreements with the experimental data for all range of ionic concentrations. The modeling results suggest that when the double layers interact, the bulk salt concentration enrichment results in the saturation of conductances for low ionic concentrations. Both the streaming conductance and the electrical conductance are enhanced by the double layer interaction, and such enhancements diminish when the channel size is larger than 10 times of the Debye length. The streaming conductance increases with pH almost linearly when pH<8, while the electrical conductance increases with pH exponentially. PMID- 20363399 TI - An ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of aflatoxins B1, B2, G1, G2, M1 and M2 in traditional Chinese medicines. AB - An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC MS/MS) method for simultaneous determination of aflatoxins B1, B2, G1, G2, M1 and M2 in traditional Chinese medicines (TCMs) was developed. The approach was characterized in details and a special focus was placed on the recovery rates of isolation procedure in different TCM matrices, i.e. rhizomes and roots, seeds, flowers, grasses and leaves. For this purpose, [(13)C(17)]-aflatoxinB1 was employed as the internal standard and a reliable solid phase extraction-based clean-up method was developed. The observed recovery rates of the six aflatoxins ranged from 85.6% to 117.6% in different matrices. Then, the established method was successfully applied to the determination of the six aflatoxins in various TCMs. For 30 commercial samples analyzed, 16 were contaminated with aflatoxins. The mean levels (incidence) of aflatoxins B1, B2, G1 and G2 in positive samples were 1.40 (68.8%), 1.27 (50.0%), 0.50 (43.8%) and 0.94 (43.8%) microg kg(-1), respectively. Interestingly, aflatoxin M1 was detected in two samples with the maximal content of 0.70 microg kg(-1). No sample was contaminated with aflatoxin M2. Meanwhile, a possible association between the contamination levels and the selected herbs was clarified in the present study. PMID- 20363400 TI - Determination of terbium in phosphate rock by Tb3+-selective fluorimetric optode based on dansyl derivative as a neutral fluorogenic ionophore. AB - For the first time a highly sensitive and selective fluorimetric optode membrane was prepared for determination of trace amounts of Tb(III) ions in phosphate rock samples. The Tb(III) sensing system was constructed by incorporating 5 (dimethylamino)-N'-(2-hydroxy-1-naphthoyl) naphthalene-1-sulfonohydrazine (L) as a neutral Tb(III)-selective fluoroionophore, in the plasticized PVC membrane containing sodium tetraphenyl borate as a liphophilic anionic additive. The response of the optode is based on the strong fluorescence quenching of L by Tb(3+) ions. At a pH value of 5.0, the optode displays a wide concentration range of 1.0 x 10(-7) to 1.0 x 10(-2)M, with a relatively fast response time of less than 45 s. In addition, to high stability and reproducibility, the sensor shows a unique selectivity towards Tb(3+) ion with respect to common cations. The optode was applied successfully to the trace determination of terbium ion in binary mixture and water samples and the determination of Tb(3+) in phosphate rock samples. PMID- 20363401 TI - Development of a fully automated sequential injection solid-phase extraction procedure coupled to liquid chromatography to determine free 2-hydroxy-4 methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid in human urine. AB - 2-Hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid, commonly known as benzophenone-3 (BZ3) and benzophenone-4 (BZ4), respectively, are substances widely used as UV filters in cosmetic products in order to absorb UV radiation and protect human skin from direct exposure to the deleterious wavelengths of sunlight. As with other UV filters, there is evidence of their percutaneous absorption. This work describes an analytical method developed to determine trace levels of free BZ3 and BZ4 in human urine. The methodology is based on a solid-phase extraction (SPE) procedure for clean-up and pre-concentration, followed by the monitoring of the UV filters by liquid chromatography-ultraviolet spectrophotometry detection (LC-UV). In order to improve not only the sensitivity and selectivity, but also the precision of the method, the principle of sequential injection analysis was used to automate the SPE process and to transfer the eluates from the SPE to the LC system. The application of a six-channel valve as an interface for the switching arrangements successfully allowed the on-line connection of SPE sample processing with LC analysis. The SPE process for BZ3 and BZ4 was performed using octadecyl (C18) and diethylaminopropyl (DEA) modified silica microcolumns, respectively, in which the analytes were retained and eluted selectively. Due to the matrix effects, the determination was based on standard addition quantification and was fully validated. The relative standard deviations of the results were 13% and 6% for BZ3 and BZ4, respectively, whereas the limits of detection were 60 and 30 ng mL( 1), respectively. The method was satisfactorily applied to determine BZ3 and BZ4 in urine from volunteers that had applied a sunscreen cosmetic containing both UV filters. PMID- 20363402 TI - Open tubular capillary electrochromatography: a useful microreactor for collagen I glycation and interaction studies with low-density lipoprotein particles. AB - Diabetes, a multifunctional disease and a major cause of morbidity and mortality in the industrialized countries, strongly associates with the development and progression of atherosclerosis. One of the consequences of high level of glucose in the blood circulation is glycation of long-lived proteins, such as collagen I, the most abundant component of the extracellular matrix (ECM) in the arterial wall. Glycation is a long-lasting process that involves the reaction between a carbonyl group of the sugar and an amino group of the protein, usually a lysine residue. This reaction generates an Amadori product that may evolve in advanced glycation end products (AGEs). AGEs, as reactive molecules, can provoke cross linking of collagen I fibrils. Since binding of low-density lipoproteins (LDLs) to the ECM of the inner layer of the arterial wall, the intima, has been implicated to be involved in the onset of the development of an atherosclerotic plaque, collagen modifications, which can affect the affinity of native and oxidized LDL for collagen I, can promote the entrapment of LDLs in the intima and accelerate the progression of atherosclerosis. In this study, open tubular capillary electrochromatography is proposed as a new microreactor to study in situ glycation of collagen I. The kinetics of glycation was first investigated in a fused silica collagen I-coated capillary. Dimethyl sulphoxide, injected as an electroosmotic flow marker, gave information about the charge of coating. Native and oxidized LDL, and selected peptide fragments from apolipoprotein B-100, the protein covering LDL particles, were injected as marker compounds to clarify the interactions between LDLs and the glycated collagen I coating. The method proposed is simple and inexpensive, since only small amounts of collagen and LDL are required. Atomic force microscopy images complemented our studies, highlighting the difference between unmodified and glycated collagen I surfaces. PMID- 20363403 TI - Gas chromatography-mass spectrometric determination of polybrominated diphenyl ethers in complex fatty matrices from aquaculture activities. AB - Gas chromatography coupled to mass spectrometry in negative chemical ionization mode (GC-(NCI)MS) has been applied to the quantification and reliable identification of polybrominated diphenyl ethers (PBDEs) in animal and vegetable samples from aquaculture activities. Matrices analyzed included fish fillet, fish feed, fish oil and linseed oil, their fat content ranged from 5% to 100%. Solid phase extraction (SPE) (using Florisil and silica cartridges) and normal-phase high performance liquid chromatography were tested for an efficient clean-up in order to obtain sample extracts free of interfering compounds. Combining sulphuric acid digestion and SPE with Florisil led to the highest efficiency in the elimination of interferences from the extracts. The sample procedure developed, together with the application of GC-(NCI)MS for measurement, led to the satisfactory determination of PBDEs at microg kg(-1) levels in complex aquaculture matrices with high lipid content. The use of a short and thin film thickness fused-silica capillary column allowed to determine the problematic BDE 209 with satisfactory results. Three m/z ions were acquired for each analyte, which ensured a reliable identification of compounds detected in samples. PMID- 20363406 TI - Cutaneous manifestations of internal malignancy. PMID- 20363407 TI - The role of endoscopy in the management of patients with peptic ulcer disease. PMID- 20363408 TI - The role of endoscopy in the management of patients with known and suspected colonic obstruction and pseudo-obstruction. PMID- 20363409 TI - Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia. AB - BACKGROUND: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE: To assess the safety and efficacy of CRYO in BE with HGD. DESIGN: Multicenter, retrospective cohort study. SETTING: Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS: CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS: CRYO is a safe and well tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD. PMID- 20363410 TI - Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy. AB - BACKGROUND: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN: Multicenter, retrospective cohort study. SETTING: Ten academic and community medical centers between 2006 and 2009. PATIENTS: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS: Complete eradication of luminal cancer and adverse events. RESULTS: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS: Retrospective study design, short follow-up. CONCLUSIONS: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer. PMID- 20363411 TI - Cryotherapy for the prevention and treatment of esophageal cancer: when does efficacy equal success? PMID- 20363412 TI - Progress in outlining the frequency and risk of recurrent neoplasia after ablation of Barrett's esophagus. PMID- 20363413 TI - Dilation in eosinophilic esophagitis: to do or not to do? PMID- 20363414 TI - Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series. AB - BACKGROUND: Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasia, the majority of data on this endoscopic modality has been provided by Japanese series. OBJECTIVE: To assess the efficacy and safety of ESD for esophageal squamous cell neoplasia in a consecutive series of patients treated in a Western setting. DESIGN AND SETTING: Single-center, prospective observational study. PATIENTS AND INTERVENTION: From January 2005 to July 2008, 20 patients with superficial esophageal squamous cell neoplasia were treated by ESD. MAIN OUTCOME MEASUREMENTS: Rates of en bloc resection, complete resection, and complications were evaluated as short-term outcomes. Overall survival, local or distant recurrence, and postoperative stricture rates were evaluated as long-term outcomes. RESULTS: ESD was performed in 20 patients (mean age 64 years, range 46 81 years; 16 men). The mean size of the lesion was 32 mm (range 15-60 mm); it was 30 mm or larger in 14 patients (70%). The mean time of ESD was 89 minutes (range 58-180 minutes). En bloc resection with resection-free margins was achieved in 18 patients (90%), whereas 2 patients presented with incomplete or indeterminate resection. Two cases (10%) of mediastinal emphysema without overt perforation and 1 case (5%) of post-ESD symptomatic stricture were reported. No local or distant post-ESD recurrence occurred in those with resection-free margins at a median follow-up of 18 months. LIMITATIONS: Small number of patients and limited follow up. CONCLUSION: This Western series study confirms that ESD is a potentially curative treatment for superficial esophageal squamous cell neoplasia. Early and late complication rates were comparable to those of Japanese series. ESD should be probably considered as the treatment of choice in all large lesions amenable to endoscopic treatment. PMID- 20363415 TI - Early endoscopic balloon dilation in caustic-induced gastric injury. AB - BACKGROUND: There are no reports on endoscopic balloon dilation (EBD) for caustic induced gastric outlet obstruction (GOO) in the acute or subacute phase. OBJECTIVE: To study the efficacy of early EBD in patients with caustic-induced gastric injury. SETTING: Tertiary care center in India. DESIGN: Retrospective analysis of data. PATIENTS: Out of 41 patients with caustic-induced GOO who reported to us in the subacute phase between January 2001 and December 2008, 31 were treated by EBD. All 31 had ingested an acid 14.39 +/- 4.65 days earlier. EBD was achieved by using wire-guided balloons under endoscopic guidance. INTERVENTION: The balloon was negotiated across the narrowed segment and inflated for 60 seconds using a pressure gun. Balloons of incremental diameter, up to a maximum of 3 sizes, were used in each sitting. Procedural success was defined as reaching the end point of dilation (15 mm) and absence of symptoms. RESULTS: All 31 patients (18 male, mean age 32.06 +/- 11.04 years) could be successfully dilated. All but 1 underwent successful dilations to achieve the end point of 15 mm, requiring a median of 9 (range 3-18) dilations over a period of 7 (range 1.5 16) weeks. Complications included self-limiting pain (n = 10), bleeding at the time of the procedure (n = 9), and perforation in 1 patient (3.2%) who required surgery. Thirty patients were followed up for a median of 21 (range 3-72) months with no recurrence. CONCLUSION: Early EBD by an expert endoscopist is a safe and effective treatment modality in the management of caustic-induced GOO. PMID- 20363416 TI - Nonampullary duodenal polyps: characteristics and endoscopic management. AB - BACKGROUND: Guidelines for endoscopic resection and surveillance of nonampullary duodenal (NAD) polyps are still not well-defined. OBJECTIVE: To describe the characteristics of NAD polyps and evaluate the role of endoscopic management. DESIGN: Retrospective review. SETTING: Tertiary-care academic center. PATIENTS: This study involved 59 patients with NAD polyps. INTERVENTION: Endoscopic polypectomy, biopsy, and argon plasma coagulation. MAIN OUTCOME MEASUREMENTS: Complete polypectomy, complications, and recurrence. RESULTS: Ninety-six endoscopies were performed. The mean patient age was 62.8 years. The mean (+/- standard deviation) polyp size was 17.2 mm +/- 1.6 mm. The mean follow-up time was 26 months. Most lesions were sessile, solitary, and located in the descending duodenum. The procedure most often performed was submucosal injection followed by snare polypectomy. Adenomas were found in 68% of lesions overall and in 84% of lesions >2 cm. Successful resection was accomplished in 93% of cases on the initial attempt. Multiple endoscopies were needed in 5% of cases. The overall complete resection rate was 98%. Recurrence was documented in 37% of cases. Complications occurred in 5.2% of patients. Polyps of >2 cm were associated with higher rates of adenoma and a higher incidence of recurrence. Colon adenomas were found in 53% of patients with duodenal adenomas. LIMITATIONS: Retrospective review. Not all patients underwent colonoscopy. CONCLUSION: NAD polyps were large, sessile, and more commonly found in the second portion of the duodenum. They are more likely to be adenomatous when the lesion size is >2 cm. Despite successful endoscopic management, over one third of lesions demonstrated recurrence. PMID- 20363417 TI - Do we need colonoscopy in patients with gastric adenomas? The risk of colorectal adenoma in patients with gastric adenomas. AB - BACKGROUND: Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes occur in gastric adenomas and colorectal adenomas. However, it is unknown whether patients with gastric adenomas are at higher risk for colorectal adenomas. OBJECTIVE: To investigate the prevalence rate of colorectal adenoma in patients with gastric adenomas and to determine the association between the presence of gastric adenomas and synchronous colorectal adenomas. DESIGN: A retrospective, cross-sectional, case control study. SETTING: Single center: Center for Health Promotion of Samsung Medical Center. PATIENTS: This study involved 87 patients with gastric adenomas and 174 sex-matched and age-matched controls among 19,019 participants who underwent EGD and colonoscopy simultaneously or within 6 months of each other from January 2001 to December 2008 at the Center for Health Promotion of Samsung Medical Center. INTERVENTION: EGD and colonoscopy. MAIN OUTCOME MEASUREMENTS: The prevalence rate of colorectal adenoma in patients with gastric adenomas. RESULTS: The 87 gastric adenoma patients included 72 men and 15 women. Colorectal adenomas were identified in 42 (48.3%) of 87 cases and in 58 (33.3%) of 174 controls (P = .022). The prevalence of colorectal adenoma was significantly higher in the gastric adenoma group than in the control group. The mean size and number of colorectal adenomas were not significantly different between the two groups. The majority of colorectal adenomas were located in distal colonic segments in the gastric adenoma group in contrast with proximal colonic segments in the control group. Multivariate logistic regression analysis revealed that independent risk factors for colorectal adenoma were the presence of gastric adenomas (odds ratio [OR], .915; 95% confidence interval [CI], 1.044-3.513) and increasing age over 55 years (OR, 2.943; 95% CI, 1.558-5.560). LIMITATIONS: Lack of data on previous colorectal adenomas and possible confounding factors such as hyperlipidemia or diabetes mellitus. CONCLUSION: The risk of colorectal adenoma increases significantly in patients with gastric adenomas and in patients over age 55. A screening colonoscopy may be necessary for patients with gastric adenomas to detect colorectal adenomas. PMID- 20363418 TI - Effect of simply recording colonoscopy withdrawal time on polyp and adenoma detection rates. AB - BACKGROUND: According to national recommendations, colonoscopy withdrawal time (WT) on negative screening examinations should average more than 6 minutes because this time is associated with a higher rate of polyp detection. Attempts have been made to increase the WT; however, simply knowing that a quality measure, such as the WT, is being monitored, by itself, may improve the quality of an examination. OBJECTIVE: To measure changes in the polyp detection rate associated with recording the WT. DESIGN: Retrospective. SETTING: Single tertiary care center. PATIENTS: Patients undergoing colonoscopy within 5 months immediately before (group A) and after (group B) initiation of WT recording. Colonoscopies were excluded if procedure times were incomplete, missing, or nonsensical. MAIN OUTCOME MEASUREMENTS: Polyp detection, compared by using the chi(2) test and logistic regression multivariate analyses; pathology manually reviewed from a sample of 200 consecutive polyp cases (100 per group). RESULTS: The average WT in group B was 14.5 minutes (11.0 minutes in negative screening examinations). In group A, polyps were detected in 530 (37.7%) of 1405 colonoscopies compared with 571 (41.2%) of 1387 colonoscopies in group B (difference 3.5%; 95% CI, -0.2% to 7.1%), a nonsignificant 9.3% relative increase. Longer procedure time, age, sex, and indication were significant predictors; monitoring the WT was not. Nonsignificantly, more polyp examinations in group B found all nonadenomas compared with group A (36% vs 27%; P = .17), and polyps were nonsignificantly smaller (P = .30). LIMITATIONS: Retrospective database data, pathology performed only on a subsample. CONCLUSION: WT recording was associated with a nonsignificant increase in polyp detection, but this was likely attributable to a slight increase in the detection of (smaller) nonadenomatous polyps. PMID- 20363419 TI - Performing a quality colonoscopy: just slow down! PMID- 20363420 TI - Inflationary caution in GI endoscopy. PMID- 20363421 TI - A meta-analysis evaluating the accuracy of colon capsule endoscopy in detecting colon polyps. AB - BACKGROUND: Colon capsule endoscopy (CCE) is a new, noninvasive method for examining the entire colon. The reported yield of CCE in detecting colorectal polyps has shown variable results. OBJECTIVE: To assess the accuracy of CCE by pooling data of existing trials. DESIGN: Meta-analysis. The fixed-effects or random-effects model was used as appropriate, based on whether homogeneity or heterogeneity, respectively, was indicated by the Cochran Q test. SETTING: Studies that estimated the accuracy of CCE were identified. Two investigators independently conducted the search and data extraction. PATIENTS: A total of 626 individuals were included in this meta-analysis. INTERVENTION: Each patient underwent CCE and conventional colonoscopy. MAIN OUTCOME MEASUREMENTS: Per patient sensitivity and specificity, with 95% confidence intervals (CI). RESULTS: Findings were categorized as "significant polyps," that is, a report of a polyp >6 mm in size or 3 or more polyps of any size, or "any polyp," that is, a report of any polyp found, independent of size. Pooled data on sensitivity and specificity with a 95% CI were estimated. For any polyp found, the pooled data showed per-patient CCE sensitivity of 73% (95% CI, 68%-77%) and specificity of 89% (95% CI, 81%-94%). For significant polyps, the respective values were 69% (95% CI, 62%-75%) and 86% (95% CI, 82%-90%). LIMITATIONS: A small number of studies met inclusion criteria. CONCLUSION: CCE is a reasonable method for screening asymptomatic individuals for colorectal polyps. It may be particularly useful for patients with "incomplete" colonoscopy, those with contraindications for conventional colonoscopy, and those unwilling to undergo colonoscopy because of its perceived inconvenience and discomfort. PMID- 20363422 TI - Endoscopic balloon dilation for obstructive colorectal cancer: a basic study on morphologic and pathologic features associated with perforation. AB - BACKGROUND: The use of endoscopic dilation and a self-expandable stent for colorectal cancer (CRC) presenting with a stricture or obstruction, either prior to surgery or as a palliative measure (an alternative to colostomy), causes perforation with relative high incidence (1%-17%). OBJECTIVE: To experimentally investigate risk factors associated with perforation in excised CRC specimens. DESIGN: Experimental study. SETTING: Ex vivo experiment on freshly excised human colon cancer specimens at an academic hospital. PATIENTS: This study involved 47 patients with strictured CRCs of <15 mm in internal diameter as assessed by a preoperative contrast enema. INTERVENTION: Immediately after surgical resection, a balloon with a diameter of 18 mm was placed in the stricture. The balloon was inflated slowly with hydrostatic pressure over 1 minute and kept at the maximum diameter for 1 minute. MAIN OUTCOME MEASUREMENTS: Correlations between macroscopic perforation and 20 items, including morphological and histopathological characteristics. RESULTS: Perforation occurred in 8 of 47 (17.0%) CRC specimens. Four items showed statistically significant (P < .05) correlations with perforation: peritumoral proliferation of collagen fibers (relative area > or =23.9% in the visual field), annularity of the tumor, severe stricture (<7.9 mm), and fewer residual smooth muscle cells in the muscularis propria, reflecting tumor encroachment. The best predictor of perforation was a combination of severe stricture and pronounced peritumoral proliferation of collagen fibers. LIMITATIONS: An uncontrolled study with a small number of patients. CONCLUSION: Histopathological and morphological items associated with a decrease in elastic compliance were more important as predictors of perforation than dilation procedure parameters, such as balloon pressure. PMID- 20363423 TI - Infection during natural orifice transluminal endoscopic surgery: a randomized, controlled study in a live porcine model. AB - BACKGROUND: Currently reported natural orifice transluminal endoscopic surgery (NOTES) procedures in animals have been done in heterogeneous milieus ranging from nonsterile to sterile procedures, with mixed results, including no infection in those performed in nonsterile settings. OBJECTIVE: To establish the potential frequency of infection during NOTES, comparing sterile to nonsterile approaches. SETTING: Survival experiments on sixteen 50-kg pigs. DESIGN AND INTERVENTIONS: From pilot data (100% infection frequency after nonsterile procedures), sample size (8 animals in each group) was calculated by using a power of 95% and an alpha risk of 0.05. The animals were randomly assigned to two groups: In the transgastric peritoneoscopy study group, liver and ovarian biopsies were performed with sterile overtubes, endoscopes, and accessories and the use of preoperative intravenous antibiotics and antiseptic gastric lavage. In the nonsterile (control) group, the same procedures were performed with nonsterile endoscopes and accessories without the use of gastric lavage and preoperative antibiotics. Complete transmural closure of the transgastric access site was made in all animals. After a 1-week survival time, all animals were killed for necropsy, which included Gram staining and peritoneal cultures. MAIN OUTCOME MEASUREMENTS: Intraperitoneal infection on necropsy. RESULTS: All necropsies revealed intraperitoneal infection (abscesses, fibrinopurulent exudates, and adhesions) in the control group (frequency of infection 100%). Peritoneal bacterial culture grew various aerobic and anaerobic organisms. No gross or bacteriological evidence of infection was seen in the sterile group (frequency of infection 0%, P value = <.0002). LIMITATIONS: Animal experiments. CONCLUSION: Nonsterile conditions invariably lead to intraperitoneal infection. Aseptic techniques during NOTES can prevent intra-abdominal infection. Future studies will determine which infection prevention steps are mandatory and which can be omitted during NOTES procedures. PMID- 20363424 TI - How to do pancreatic mass FNA. AB - FNA is an important aspect in the diagnosis and management of pancreatic masses. Studies have shown that the overall accuracy of EUS-guided FNA ranges between 71% and 90% in this setting. It is important to review all pertinent clinical data (especially cross-sectional imaging) before performing endoscopy. The choice of needle may depend on the location and size of the lesion. Once the lesion is targeted and placed in optimal position, FNA is performed under total EUS guidance while visualizing the needle tip at all times. Factors that may increase the diagnostic yield of FNA include sampling the lesion in multiple planes, targeting the margins or firmer ends of a necrotic mass, and arranging for ROSE. PMID- 20363425 TI - Endoscopic management of a tubular esophageal duplication diagnosed in adolescence (with videos). AB - BACKGROUND: Esophageal duplication is a rare congenital lesion. Surgery is the standard treatment. Tubular duplication is extremely rare, with esophageal communication in very few cases. OBJECTIVE: The aim of this study was to document the feasibility of the endoscopic management of tubular esophageal duplication. DESIGN: Case report. INTERVENTION: A 14-year-old boy presented with acute dysphagia and acute retrosternal pain. Based on his radiographic and endoscopic findings, a cystic esophageal duplication with an upper esophageal stricture was initially suspected. A laparoscopic gastrostomy was performed. A cyst resection through right thoracoscopy assisted by flexible endoscopy was decided upon. When no extraluminal cystic duplication was found, a tubular duplication was considered and the procedure was abandoned. An endoscopic treatment was performed. A standard endoscope was inserted through an upper esophageal stricture. Two lumens were identified 25 cm from the incisors. A pediatric endoscope was passed through the main one, revealing a thick intraluminal bridge. By using a guidewire, the endoscope's passage into the narrow lumen revealed a distal communication with the esophagus. With the guidewire left in place, the endoscope was reintroduced into the main lumen. A lengthwise incision of the bridge was performed by using a needle knife. At the end of the procedure, an esophageal dilation was performed. Histology confirmed the diagnosis of duplication. RESULTS: The endoscopic incision of the duplication was completed uneventfully. For 11 months, the patient followed a normal diet and experienced no symptoms. LIMITATIONS: Single case. CONCLUSION: To our knowledge, this is the first report of successful endoscopic incision of a total tubular esophageal duplication. PMID- 20363426 TI - A novel method of full-thickness gastric biopsy via a percutaneous, endoscopically assisted, transenteric approach. AB - BACKGROUND: Pathologic changes of the enteric nervous system of the stomach have been described in gastroparesis. Because the enteric nervous system lies within the myenteric plexus between the muscle layers of the stomach, it is not accessible by standard biopsy forceps. Thus, tissue must be obtained by laparoscopy or laparotomy. Obtaining full-thickness biopsies with a less-invasive method would be an ideal alternative. OBJECTIVE: To assess the safety and feasibility of a novel method of gastric, full-thickness biopsy by using a percutaneous, endoscopically assisted, transenteric approach. DESIGN: Experimental pilot study in 3 dogs, approved by the animal care committee. INTERVENTION: Under general anesthesia, dogs underwent gastroscopy, and a suitable biopsy area was chosen, based on indentation of the anterior stomach wall by external finger pressure on the abdominal skin and by endoscope transillumination. Using sterile technique, we made a 3-mm incision through the abdominal skin, and a spring-loaded, 14-gauge biopsy needle was used to take 4 separate antral biopsies from each dog, with no mucosal or abdominal closure intervention. MAIN OUTCOME MEASUREMENTS: Feasibility of obtaining enteric nervous system tissue; morbidity and mortality at 4 weeks; gross pathology at necropsy. RESULTS: The procedure was well tolerated by the dogs, with no morbidity or mortality at any time, up to 4 weeks after the procedure. Adequate tissue specimens were obtained for histologic analysis of all layers of the stomach, including enteric nervous system elements. LIMITATIONS: Biopsy size was smaller than a surgical biopsy size. CONCLUSION: The percutaneous, endoscopically assisted, transenteric approach, full-thickness biopsy technique is safe and obtains enteric nervous tissue in a simple, minimally invasive manner. PMID- 20363427 TI - Laying the foundation for NOTES: another brick in the wall. PMID- 20363428 TI - Unusual cause of acute airway collapse. PMID- 20363429 TI - Unusual cause for upper GI bleeding: a splenic artery aneurysm mimicking a Dieulafoy lesion. Role for systematic EUS assessment? PMID- 20363430 TI - Disappearance of an ampullary pseudotumor after steroid therapy for autoimmune pancreatitis. PMID- 20363431 TI - EUS-guided biopsy for the diagnosis and classification of lymphoma. AB - BACKGROUND: EUS-guided FNA and Tru-cut biopsy (TCB) is highly accurate in the diagnosis of lymphoma. Subclassification, however, may be difficult in low-grade non-Hodgkin lymphoma and Hodgkin lymphoma. OBJECTIVE: To determine the yield of EUS-guided biopsy to classify lymphoma based on the World Health Organization classification of tumors of hematopoietic lymphoid tissues. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 24 patients referred for EUS-guided biopsy who had a final diagnosis of lymphoma or "highly suspicious for lymphoma." INTERVENTIONS: EUS-guided FNA and TCB combined with flow cytometry (FC) analysis. MAIN OUTCOMES MEASUREMENT: Lymphoma subclassification accuracy of EUS guided biopsy. RESULTS: Twenty-four patients were included in this study. Twenty-three patients underwent EUS-FNA, and 1 patient had only TCB. Twenty-two underwent EUS-TCB combined with FNA. EUS correctly diagnosed lymphoma in 19 out of 24 patients (79%), and subclassification was determined in 16 patients (66.6%). Flow cytometry correctly identified B-cell monoclonality in 95% (18 out of 19). In 1 patient diagnosed as having marginal-zone lymphoma by EUS-FNA/FC only, the diagnosis was changed to hairy cell leukemia after a bone marrow biopsy was obtained. EUS had a lower yield in nonlarge B-cell lymphoma (only 9 out of 15 cases [60%]) compared with large B-cell lymphoma (78%; P = .3 [Fisher exact test]). LIMITATIONS: Retrospective, small number of patients. CONCLUSION: EUS-guided biopsy has a lower yield to correctly classify Hodgkin lymphoma and low-grade lymphoma compared with high-grade diffuse large B-cell lymphoma. PMID- 20363432 TI - Endoscopic hemostasis with fibrin glue for refractory postsphincterotomy and postpapillectomy bleeding. AB - BACKGROUND: Bleeding is a feared complication of endoscopic sphincterotomy and papillectomy. Fibrin glue has been proposed as an effective adjunct in securing hemostasis. However, its use has been limited by the risk of early occlusion of the injecting needle, and its role has not been defined in the setting of refractory post-ERCP bleeding. We present a modified technique of endoscopic hemostasis with diluted fibrin glue in the setting of postsphincterotomy and postpapillectomy bleeds. OBJECTIVE: We aimed to verify that diluted fibrin glue can be easily and successfully injected and is effective in the endoscopic treatment of refractory post-ERCP bleeding. DESIGN: Case series. SETTING: A tertiary-care academic medical center. PATIENTS: Six patients with refractory post-ERCP bleeding were treated (3 after sphincterotomy and 3 after papillectomy) with fibrin glue injection. INTERVENTION: Endoscopic hemostasis with diluted fibrin glue injection. MAIN OUTCOME MEASUREMENTS: Successful endoscopic hemostasis with diluted fibrin glue injection. RESULTS: One session of fibrin glue injection stopped the refractory post-ERCP bleeding in all 6 patients. LIMITATION: Small number of patients. CONCLUSION: This case series provides evidence that our modified injection technique of diluted fibrin glue allowed an easy submucosal injection and may be considered to be an effective endoscopic modality to treat refractory post-ERCP bleeding. PMID- 20363433 TI - Small-bowel lesions caused by portal hypertension of schistosomal origin: a capsule endoscopy pilot study. AB - BACKGROUND: Schistosomiasis is a highly prevalent disease. It can evolve to its hepatosplenic form in up to 10% of the cases. The small-bowel lesions developed during the hepatosplenic stage of the disease have not been described in vivo. OBJECTIVE: The aim of this study was to describe, for the first time, in a pilot study, the endoscopic aspects of the lesions in the small bowel of patients with portal hypertension due to schistosomiasis, using the PillCam SB, and to determine the usefulness of the method for the diagnosis of esophageal varices. DESIGN: Case series. SETTING: Tertiary-care medical center. PATIENTS: Nine nonrandomized patients with hepatosplenic schistosomiasis and esophageal varices without previous GI bleeding were selected based on findings from the PillCam SB. Patients using medications that could alter the coagulation, with history of abdominal surgery, who were undergoing treatment of the portal hypertension other than beta-blocker, and with symptoms suggesting bowel obstruction were excluded. The findings were interpreted by a single endoscopist. RESULTS: Capsule endoscopy was able to diagnose esophageal varices in all 9 patients. All of the patients presented angioectasias and venectasias in the small bowel. Small-bowel varices were present in 22.2% of the patients; edema and erosions were found in 66.7% and 88.9%, respectively. Lesions of so-called "scarred mucosa" were found in 55.5% of the patients. LIMITATIONS: Small number of patients; case series. CONCLUSION: The PillCam SB was effective, giving a significant contribution to the description of the esophageal varices and small-bowel lesions of the patients with portal hypertension caused by Schistosoma mansoni. PMID- 20363435 TI - Primary incision of esophageal strictures: the technical details? PMID- 20363436 TI - Peroral direct cholangioscopy with an ultraslim gastroscope in combination with a short double-balloon enteroscope in patients with altered GI anatomy. PMID- 20363440 TI - The Journal of Surgical Research Editorial Board--2010. PMID- 20363438 TI - Balloon sweep in portal biliopathy. PMID- 20363441 TI - Targeted gene delivery to selected liver segments via isolated hepatic perfusion. AB - BACKGROUND: Development of targeted gene transfer technologies is essential for in vivo gene therapy. In this study, we examined the feasibility of physically targeting an adenoviral vector to selected liver segments in rats by isolating the hepatic perfusion (IHSP) and clamping the portal vein between the upper and lower segments. MATERIALS AND METHODS: The rats were divided into two groups: IHSP group and the inferior vena cava (IVC) group. The adenoviral vector, which harbored the beta-galactosidase (beta-gal) gene, was administered via the portal vein, after which unbound vector particles were washed out with phosphate buffered saline (PBS) and removed via the cannulated inferior vena cava (IVC) in IHSP group, while the IVC group received the transgene directly via the IVC without isolation of the hepatic perfusion. RESULTS: With this configuration (IHSP group), >99% of the beta-gal activity was limited to the targeted hepatic lobes, findings which were confirmed by histochemical staining with X-gal. We also found there to be significant differences in transgene expression among the hepatic lobes in the IVC group. CONCLUSIONS: Taken together, these results indicate that the IHSP technique is useful for local gene delivery to selected liver segments, and that when evaluating the efficacy of IHSP in the treatment of liver disease (e.g., nonresectable tumors), interlobar differences must be given careful consideration to ensure that sufficient drug or vector is delivered to all targeted hepatic lobes. PMID- 20363442 TI - Drug resistance in ovarian cancer: biomarkers and treatments Highlights from the DROC meeting held in Modena (Italy) on the 19th and 20th of February 2009. Scientific topics discussed at the meeting are reported in the present issue. PMID- 20363443 TI - Significant advances in the delivery of health care. Preface. PMID- 20363444 TI - Crossing the quality chasm in neonatal-perinatal medicine. AB - The "Quality Chasm" exists in neonatal intensive care. Despite years of clinical research in neonatology, therapies continue to be underused, overused, or misused. A key concept in crossing the quality chasm is system redesign. The unpredictability of human factors and the dynamic complexity of the neonatal ICU are not amenable to rigid reductionist control and redesign. Change is best accomplished in this complex adaptive system by use of simple rules: (1) general direction pointing, (2) prohibitions, (3) resource or permission providing. These rules create conditions for purposeful self-organizing behavior, allowing widespread natural experimentation, all focused on generating the desired outcome. PMID- 20363445 TI - Evaluating the medical evidence for quality improvement. AB - Neonatal-Perinatal Medicine has had both its triumphs and its disasters regarding the dissemination of new interventions. Evidence-based medicine (EBM), the integration of clinical expertise, patient values, and best evidence for decision making in patient care, provides a blueprint for how to safely and effectively continue make headway in our rapidly changing field. The principles of EBM have been discussed in multiple articles and primers. EBM involves formulating the appropriate question, finding the evidence, appraising the evidence, and evaluating the clinician's performance in implementing these practices. At an institutional level, this type of thorough evidence review is critical to successful quality improvement projects, particularly if these projects hope to improve clinical outcome. On evaluation of best practice, one sees great variation in the implementation of practices that are strongly evidence based (increased use of antenatal steroids, decreased use of postnatal steroids), practices rich in evidence lacking certainty regarding the best approach (prophylactic indomethacin to prevent intraventricular hemorrhage), and widespread dissemination of practices that have little evidence to support their use (stabilization on high-frequency ventilation). PMID- 20363446 TI - The Vermont Oxford Network: a community of practice. AB - The Vermont Oxford Network is a not-for-profit organization established in the late 1980s with the goals of improving the quality and safety of medical care for newborn infants and their families through a coordinated program of research, education, and quality improvement. In this paper the authors discuss the activities and programs sponsored by the Network to achieve those goals. PMID- 20363447 TI - The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system--tools for "meaningful use" in continuous quality improvement. AB - The Pediatrix BabySteps Clinical Data Warehouse (CDW) is a rich and novel tool allowing unbiased extraction of information from an entire neonatal population care by physicians and advanced practice nurses in Pediatrix Medical Group. Because it represents the practice of newborn medicine ranging from small community intensive care units to some of the largest neonatal intensive care units in the United States, it is highly representative of scope of practice in this country. Its value in defining outcome measures, quality improvement projects, and research continues to grow annually. Now coupled with the BabySteps QualitySteps program for defined clinical quality improvement projects, it represents a robust methodology for meaningful use of an electronic health care record, as designated during this era of health care reform. Continued growth of the CDW should result in continued important observations and improvements in neonatal care. PMID- 20363448 TI - The role of regional collaboratives: the California Perinatal Quality Care Collaborative model. AB - Improving the outcome of the infants cared for in one's neonatal intensive care unit is the main objective of improvement projects that are pursued independently or as a member of a national collaborative. Regional quality improvement collaborations represent the intersection of hospital-based and community-based medicine offering the possibility of coordinated improvement efforts conducted at both the hospital and community level. This article discusses the aspirations, workings, and achievements of the California Perinatal Quality Care Collaborative, a regional collaboration formed to improve perinatal care. While it is never easy to align the often differing fundamental positions held by the various member factions and stakeholder groups, the common goal of a universally agreed-upon mission statement can act as a magnet drawing the various components together. Rapid development of a first quality improvement initiative is an effective strategy to engage the participants in a way that allows them to demonstrate, share, and build upon their individual expertise, and provides them a strong sense of professional accomplishment. PMID- 20363449 TI - A primer on quality improvement methodology in neonatology. AB - This article provides a systematic and pragmatic approach to quality improvement in the neonatal intensive care unit setting. The "model for improvement" serves as the foundation for the approach, and is based on three core questions, followed by cycles of testing: What are we trying to accomplish? How will we know that a change represents an improvement? What changes can we make that will result in continuous improvement? This article reviews these questions in detail and provides specific examples to highlight the practical use of this methodology. PMID- 20363450 TI - Navigating in the turbulent sea of data: the quality measurement journey. AB - This article provides a roadmap for your quality measurement journey. It begins with a discussion of 3 approaches to measurement (improvement, accountability and research) and challenges readers to be clear about why they are measuring. Key milestones along the quality measurement journey are then presented and a framework for selecting measures, developing clear operational definitions, building data collection plans, and understanding the variation that exists in data is outlined. The article ends with a discussion of why data need to be linked to improvement strategies. PMID- 20363451 TI - Human factors and quality improvement. AB - Human factors analysis (HFE) presents a formidable contribution to quality improvement (QI) in the neonatal intensive care unit (NICU). The science behind the fundamental principles concerning the design of work systems that match the needs of the people who work in them is sound and is applied widely in other safety critical situations. Early application of HFE in NICUs has shown the usefulness of these methods for frontline teams working to improve quality, reliability, and safety. The inclusion of human factors considerations in the design of structure and process has the potential to improve outcomes for patients and families and to improve the comfort and usability of work systems for providers who work in them. New technologies and continual change must be informed and designed through the application of HFE methods and principles to realize the full potential of QI. PMID- 20363452 TI - Random safety auditing, root cause analysis, failure mode and effects analysis. AB - Improving quality and safety in health care is a major concern for health care providers, the general public, and policy makers. Errors and quality issues are leading causes of morbidity and mortality across the health care industry. There is evidence that patients in the neonatal intensive care unit (NICU) are at high risk for serious medical errors. To facilitate compliance with safe practices, many institutions have established quality-assurance monitoring procedures. Three techniques that have been found useful in the health care setting are failure mode and effects analysis, root cause analysis, and random safety auditing. When used together, these techniques are effective tools for system analysis and redesign focused on providing safe delivery of care in the complex NICU system. PMID- 20363453 TI - Pay for performance in neonatal-perinatal medicine--will the quality of health care improve in the neonatal intensive care unit? A business model for improving outcomes in the neonatal intensive care unit. AB - Because neonatal medicine is such an expensive contributor to health care in the United States--with a small population of infants accounting for very high health care costs--there has been a fair amount of attention given to this group of patients. An idea that has received increasing attention in this discussion is pay for performance. This article discusses the concept of pay for performance, examines what potential benefits and risks exist in this model, and investigates how it might achieve the desired goals if implemented in a thoughtful way. PMID- 20363454 TI - Collaboration between obstetricians and neonatalogists: perinatal safety programs and improved clinical outcomes. AB - Although collaboration between obstetricians and neonatologists may seem an obvious way to provide the best quality care to infants and their mothers, this has not always occurred. This article highlights the experiences of several recently published efforts demonstrating how coordinated care resulted in improved clinical outcomes. PMID- 20363455 TI - Delivery room intervention: improving the outcome. AB - The authors have conducted video review of neonatal resuscitations since 1999. Over this 10-year period 3 phases of our experience have been recognized. Our early reviews helped us recognize what we were doing in the delivery room, an area that had been ignored in improved intervention. It was noted that on many occasions multiple people were trying to accomplish the same task, that bag and mask ventilation was almost exclusively the purview of the respiratory therapists and was not performed well by others, and that infants with low birth weight were often hypothermic on admission. After determining what was being done and how well it was being done, we moved on to how to do it better. This period included making environmental changes by warming the room, the use of occlusive wrap, determining the effectiveness of bag and mask ventilation with colorimetric CO(2) detectors, and the introduction of crew resource management to develop consistent and effective communication. The third and current phase of our experience is to determine how these interventions affect delivery room and potentially later outcomes. Well-designed clinical trials are still needed to further establish the most optimal resuscitation interventions. PMID- 20363456 TI - Comprehensive Oxygen Management for the Prevention of Retinopathy of Prematurity: the pediatrix experience. AB - Comprehensive oxygen management, focused on avoiding hyperoxia and repeated episodes of hypoxia-hyperoxia in very low birth weight infants, has been successfully used for the reduction of retinopathy of prematurity. Building on this experience, the Comprehensive Oxygen Management for the Prevention of Retinopathy of Prematurity quality improvement initiative was developed to facilitate the spread and refinement of these techniques. The initiative focused on staff education and evaluation and redesign of the processes and practices involving oxygen use. Monitoring of the effectiveness of the system changes was supported through audits of clinical practice changes, use of oxygen saturation trending data, and the incidence of retinopathy of prematurity. PMID- 20363458 TI - Decreasing central line associated bloodstream infection in neonatal intensive care. AB - Central Line Associated Bloodstream Infections (CLABSIs) have come to be recognized as preventable adverse events that result from lapses in technique at multiple levels of care. CLABSIs are associated with increased mortality and adverse outcomes that may have lifelong consequences. This review provides a summary of evidence-based strategies to reduce CLABSI in the newborn intensive care unit that have been described in the literature over the past decades. Implementation of these strategies in "bundles" is also discussed, citing examples of successful quality improvement collaboratives. The methods of implementation require an understanding of the scientific data and technical developments, as well as knowledge of how to influence change within the unique and complicated milieu of the newborn intensive care unit. PMID- 20363459 TI - Quality improvement in respiratory care: decreasing bronchopulmonary dysplasia. AB - Chronic lung disease (CLD) is one of the most common long-term complications in very preterm infants. Bronchopulmonary dysplasia (BPD) is the most common cause of CLD in infancy. Modern neonatal respiratory care has witnessed the emergence of a new BPD that exhibits decreased fibrosis and emphysema, but also decreased alveolar septation, and microvascular development. CLD encompasses the classic and the new BPD, and recognizes that lung injury can occur in term infants who need aggressive ventilatory support and who develop lung injury as a result, and that CLD is a multisystem disease. Controversy exists on whether quality improvement (QI) methods that implement multiple interventions will be effective in limiting pathology with multiple causes. Caution in generalization of QI findings is encouraged. QI methods toward improvement in CLD or any other outcome should be considered as a tool for implementing evidence and studying the effects of change in complex adaptive systems. PMID- 20363460 TI - 'International' is the new 'European'. PMID- 20363457 TI - Improving the use of human milk during and after the NICU stay. AB - The feeding of human milk (milk from the infant's own mother; excluding donor milk) during the newborn intensive care unit (NICU) stay reduces the risk of costly and handicapping morbidities in premature infants. The mechanisms by which human milk provides this protection are varied and synergistic, and appear to change over the course of the NICU stay. The fact that these mechanisms include specific human milk components that are not present in the milk of other mammals means that human milk from the infant's mother cannot be replaced by commercial infant or donor human milk, and the feeding of human milk should be a NICU priority. Recent evidence suggests that the impact of human milk on improving infant health outcomes and reducing the risk of prematurity-specific morbidities is linked to specific critical exposure periods in the post-birth period during which the exclusive use of human milk and the avoidance of commercial formula may be most important. Similarly, there are other periods when high doses, but not necessarily exclusive use of human milk, may be important. This article reviews the concept of "dose and exposure period" for human milk feeding in the NICU to precisely measure and benchmark the amount and timing of human milk use in the NICU. The critical exposure periods when exclusive or high doses of human milk appear to have the greatest impact on specific morbidities are reviewed. Finally, the current best practices for the use of human milk during and after the NICU stay for premature infants are summarized. PMID- 20363461 TI - Evaluation of adverse events in cats receiving long-term piroxicam therapy for various neoplasms. AB - The role of cyclo-oxygenase 2 (COX-2) and prostaglandins (PG) in carcinogenesis has been documented in many species. Piroxicam has shown efficacy against several neoplasms and is frequently prescribed for chronic use. There are no studies investigating chronic piroxicam administration in cats and the chronic use of non steroidal anti-inflammatory agents in this species has long been cautioned against. This retrospective study aimed to evaluate adverse effects in cats receiving long-term daily piroxicam. Seventy-three cats received daily piroxicam at doses of 0.13-0.41mg/kg. Treatment duration ranged from 1 to 38 months. Treatment with piroxicam was found to significantly increase frequency of vomiting during the first month of therapy, though this was most significant for cats receiving concurrent chemotherapy. Piroxicam administration was not significantly associated with hematologic, renal or hepatic toxicities. Adverse events were not correlated with dosage. Adverse events were reported in 29% of cats, and were generally mild and transient. Eight percent discontinued piroxicam due to adverse reaction, and 4% due to difficult administration. This study indicates that long-term daily piroxicam is generally well tolerated in cats at conventional doses. PMID- 20363464 TI - Congenital hypogonadotropic hypogonadism in females: clinical spectrum, evaluation and genetics. AB - Congenital hypogonadotropic hypogonadisms (CHH) are a well-known cause of pubertal development failure in women. In a majority of patients, the clinical spectrum results from an insufficient and concomitant secretion of both pituitary gonadotropins LH and FSH that impedes a normal endocrine and exocrine cyclical ovary functioning after the age of pubertal activation of gonadotropic axis. In exceptional but interesting cases, they can result from an elective deficit of one of the gonadotropins follicle-stimulating hormone (FSH) or luteinizing hormone (LH) by genetic anomaly of their specific ss sub-unit. CHH prevalence, estimated from teaching hospital series, is considered to be two to five fold less important in women compared to men bearing the disease. This frequency is probably under-estimated in reason of under-diagnosis of forms with partial pubertal development. Isolated or apparently isolated forms (i.e., Kallmann syndrome with anosmia or hyposmia not spontaneously expressed by the patients) of these diseases are most of the time discovered during adolescence or in adulthood in reason of lacking, incomplete or even apparently complete pubertal development, but with almost constant primary amenorrhea. In a minority of cases and mainly in familial forms, genetic autosomal causes have been found. These cases are related to mutations of genes impinging the functioning of the pituitary-hypothalamic pathways involved in the normal secretion of LH and FSH (mutations of GnRHR, GnRH1, KISS1R/GPR54, TAC3, TACR3), which are always associated to isolated non syndromic CHH without anosmia. Some cases of mutations of FGFR1, and more rarely of its ligand FGF8, or of PROKR2 or its ligand PROK2 have been shown in women suffering from Kallmann syndrome or its hyposmic or normosmic variant. In complex syndromic causes (mutations of CHD7, leptin and leptin receptor anomalies, Prader-Willi syndrome, etc.), diagnosis of the CHH cause is most often suspected or set down before the age of puberty in reason of the associated clinical signs, but some rare cases of paucisymptomatic syndromic causes can initially be revealed during adolescence, like isolated non syndromic CHH or Kallmann syndrome. PMID- 20363465 TI - Do PTSD symptoms and course predict continued substance use for homeless individuals in contingency management for cocaine dependence? AB - Homeless individuals (n=187) entering contingency management (CM) for cocaine dependence were assessed for PTSD diagnosis, and a subset of 102 participants reporting traumatic exposure also periodically completed a self-report measure of PTSD symptoms. Patients with PTSD in full remission at 6 months (end of active treatment) and 12 months (end of aftercare) used substances much less frequently during aftercare than those with no PTSD diagnosis. Those whose PTSD diagnosis improved to full remission status during active treatment, and remained in full remission at 12 months, also had superior substance use outcomes. Severity of PTSD symptoms at 6 months, but not baseline or 2 months, was associated with substance use across treatment phases. Substance use during aftercare, however, was better predicted by changes in PTSD symptom severity. Patients whose PTSD symptoms improved more during active treatment fared better during aftercare than those with less improvement. Findings suggest homeless individuals with comorbid PTSD entering CM for cocaine dependence are not necessarily at increased risk for substance use compared to those without the comorbidity. However, course of PTSD does predict substance use, with the potential for CM to be unusually effective for those who respond with substantial, lasting improvements in PTSD. PMID- 20363466 TI - Monovalent and bivalent N-fucosyl amides as high affinity ligands for Pseudomonas aeruginosa PA-IIL lectin. AB - The adhesion of bacteria to human glycoconjugates can be inhibited by soluble glycomimetics that compete with the natural target. Four monovalent and one divalent alpha-fucosyl amides have been tested for their affinity for a fucose binding lectin from Pseudomonas aeruginosa. Isothermal calorimetric titrations demonstrated that they bind to the lectin in the micromolar range, with highest affinity for the divalent ligand. Molecular modelling established that, compared to Omicron-fucoside compounds, the glycomimetic amide group resulted in the loss of water-bridged hydrogen bonds that could be partially compensated by additional contact of the aglycone with the protein surface. PMID- 20363467 TI - Synthesis of alkyl and cycloalkyl alpha-d-mannopyranosides and derivatives thereof and their evaluation in the mycobacterial mannosyltransferase assay. AB - The synthesis of a series of alkyl (having from C6 to C20 aglycones), cyclohexyl, and cyclohexylalkyl alpha-d-mannopyranosides, 6-deoxygenated analogs, thioglycosides, and sulfones derived thereof, is reported. Here, under the in vitro assay conditions used, none of the 15 tested compounds acted as an inhibitor of the mannose transfer catalyzed by the enzymes present in mycobacterial membrane and cell wall fractions. Mannopyranosides comprising shorter aliphatic, up to 8 carbon atoms long linear, or cyclic aglycone served as the acceptor substrates in the mycobacterial mannosyltransferase reaction. The thioglycosides exhibited similar behavior, in contrast to the sulfones, which were essentially not recognized by the mycobacterial enzymes. 6-Deoxygenated glycosides were not processed by the enzymes, suggesting that the mannose transfer occurs at position 6 of the acceptors. PMID- 20363468 TI - A fast, efficient and stereoselective synthesis of hydroxy-pyrrolidines. AB - A five-step, protecting group free synthesis of 2,3-cis substituted hydroxy pyrrolidines is presented. Key steps in the synthesis are the chemoselective formation of a primary amine via a Vasella reductive amination using ammonia as the nitrogen source, and the stereoselective formation of a cyclic carbamate from an alkenylamine. Improvement of the reductive amination, by way of the use of alpha-picoline borane as a more environmentally benign reducing agent, is also presented. PMID- 20363469 TI - First words and first memories. AB - In two experiments autobiographical memories from childhood were recalled to cue words naming common objects, locations, activities and emotions. Participants recalled their earliest specific memory associated with each word and dated their age at the time of the remembered event. A striking and specific finding emerged: age of earliest memory was systematically later, by several months, than the age of acquisition of the word to which it was associated. This was the case for earlier and later acquired words, for all word types, and for younger as well as older adults. It is suggested that this systematic lag reflects the formation of conceptual knowledge that is abstracted from details represented in early episodic memories. It is not until such knowledge is formed that a word cue and the conceptual knowledge in long-term to which it corresponds, can be used to access specific episodic memories. The implications of this for understanding childhood amnesia and for theories of the development of autobiographical memory are considered. PMID- 20363470 TI - A dramatic shift in CO and CH4 levels at urban locations in Korea after the implementation of the Natural Gas Vehicle Supply (NGVS) program. AB - Concentrations of carbon monoxide (CO) and methane (CH(4)) in air were measured at both urban roadside (U-RS) and urban background (U-BG) stations in Seoul, Korea over an 11 yr period (1996-2006). The overall mean values of CO were 1.16+/ 0.63 (U-RS) and 1.08+/-0.77 ppm (U-BG), while those of CH(4) were 2.24+/-0.42 (U RS) and 2.06+/-0.31 ppm (U-BG). The diurnal patterns of CO tended to peak near rush hour, while those of CH(4) showed increases at night. An examination of the seasonal data showed that the CO values were consistently higher during winter, while CH(4) values were highly variable across seasons with relatively large spatial variations. Because of the noticeable change in air quality parameters after the year 2000, the mean data for both compounds were examined between 1996 2000 (period I) and 2001-2006 (period II). The analysis of long-term trends revealed that the concentrations of both compounds decreased very rapidly during period I, while changes were not significant during period II. The results of this comparative study confirm that both urban locations have experienced dramatic changes in the major pollutant levels, particularly in CO after the implementation of the Natural Gas Vehicle Supply (NGVS) program. PMID- 20363471 TI - Phospholipase A2s: developing drug targets for atherosclerosis. AB - The potential for phospholipases as targets for treating atherogenesis has become more prominent over the past year with the publication of the results of Phase 2 clinical trials of two inhibitors of forms of phospholipase A2: darapladib (GSK) which inhibits lipoprotein-associated phospholipase A2 and varespladib (Anthera) an inhibitor of several secreted phospholipase A2s. Although some aspects of their biology overlap, these are distinct targets with different potential for influencing atherogenesis. The background science to these two targets is discussed in this review, noting the balance of data, from human, preclinical species and in vitro that support further development of the inhibitors into Phase 3. Note is taken of another phospholipase A2 (cytosolic) which has been less fully described but for which there has been some interest. PMID- 20363472 TI - Relationship between visceral fat accumulation and urinary albumin-creatinine ratio in middle-aged Japanese men. AB - OBJECTIVE: Chronic kidney disease including microalbuminuria relates to cardiovascular disease (CVD). Microalbuminuria is also known to be a marker of generalized endothelial dysfunction. The metabolic syndrome which encompasses visceral fat accumulation and various metabolic disorders, has also an increase in albuminuria and relates to CVD. However, the relationship between visceral fat accumulation and albuminuria remains to be defined. The present study investigated the relationship between visceral fat accumulation and urinary albumin-creatinine ratio (UACR) in Japanese men. METHODS: This study group comprised 1990 Japanese male subjects, who were employees of a city office, had undergone annual health check-up. Urinary albumin was collected from a single spot urine specimen collected anytime between morning and afternoon. Visceral fat area was estimated (eVFA) by the bioelectrical impedance analysis method. RESULTS: Log-UACR correlated with age, log-body mass index (BMI), log-waist circumference (WC), log-eVFA, log-adiponectin, blood pressure, serum lipids and hemoglobin A1c (HbA1c). Stepwise multiple regression analysis identified log eVFA, as well as HbA1c, blood pressure, log-TG, and age, as a significant determinant of log-UACR. Moreover, subjects with eVFA > or = 100 cm(2) had significantly higher UACR than those with eVFA <100 cm(2), irrespective of BMI. UACR was significantly worse in subjects with high numbers of metabolic risk factors, and moreover in subjects with eVFA > or = 100 cm(2) than in those with eVFA <100 cm(2). CONCLUSION: These results suggested that visceral fat accumulation is associated with an increase in UACR. Evaluation of both visceral fat accumulation and urinary albumin may be important for preventing atherosclerotic diseases. PMID- 20363473 TI - Carbon nanocones/disks as new coating for solid-phase microextraction. AB - In this article, the potential of carbon nanocones/disks as coating for solid phase microextraction has been evaluated for the first time. The nanostructures were immobilized on a stainless steel needle by means of an organic binder. The fiber coating obtained was ca. 50 microm of thickness and 35 mm in length. The evaluation of the sorbent capacity was carried out through the determination of toluene, ethylbenzene, xylene isomers and styrene in water samples following the headspace sampling modality (15 min, 30 degrees C). The fiber was then transferred to a 10 mL vial which was sealed and heated at 110 degrees C for 15 min in the headspace module of the instrument to achieve the thermal desorption of the analytes. Then 2.5 mL of the headspace generated were injected in the gas chromatograph-mass spectrometer for analytes separation and quantitation. The detection and quantitation limits obtained for 10 mL of sample were 0.15 and 0.5 ng mL(-1) (0.6 and 2 ng mL(-1) for toluene). The optimized procedure was applied to the determination of the selected volatile compounds in waters collected from different locations. The recovery values obtained (average recovery ca. 92%) demonstrated the usefulness of the carbon nanocones/disks as sorbent material in solid-phase microextraction. PMID- 20363474 TI - Design of pseudo-simulated moving bed process with multi-objective optimization for the separation of a ternary mixture: linear isotherms. AB - Pseudo-SMB, often called "J-O process", is a modified SMB process to completely separate a ternary mixture with two discrete steps per one cycle. For improved separation, two new design parameters, the position of step 1 (chi(S1)) and the number of port switches during step 2 (n(SMB)), were introduced. A multi objective optimization method was used to optimize the operating conditions of the pseudo-SMB process with four average zone flow-rate ratios for one cycle. Nadolol isomers were selected for the model solutes and the global objective for the design of the pseudo-SMB was to collect 99% of the intermediate retained solute. The separation was optimized for 8-column pseudo-SMB system with three column lengths (2.5, 5.0, and 10 cm) and three feed composition ratios (1/1/1, 1/2/1, and 2/1/2). The simulation results showed that productivity was increased 4.3 times (n(SMB)=20, chi(S1)=0.5, 1/1/1) and desorbent to feed ratio D/F was decreased 45% (n(SMB)=16, chi(S1)=0.5, 1/1/1) compared to normal operation (n(SMB)=8, chi(S1)=0.5, 1/1/1). Productivity and D/F were significantly improved when short columns were used in the pseudo-SMB process. The pseudo-SMB was compared with recycle chromatography and SMB cascades for the same total amount of adsorbent. Recycle chromatography and 8-column SMB cascades using 20 cm and 40 cm of total column lengths were not able to separate the intermediate component with the target purity and the same feed rate of the pseudo-SMB process. PMID- 20363475 TI - Interaction of annexin A6 with cholesterol rich membranes is pH-dependent and mediated by the sterol OH. AB - Annexin A6 (AnxA6), a calcium- and membrane-binding protein, is well-known to play a role in calcium homeostasis, membrane traffic and membrane organization. It had been suggested that, despite calcium-dependent interaction with anionic phospholipids, AnxA6 displays calcium-independent cholesterol binding properties. In this study, the following questions were addressed: does AnxA6 bind preferentially to cholesterol-containing biomimetic membranes? If so, what is the molecular mechanism of the binding? To answer these questions, human recombinant AnxA6-1 isoform was prepared and used with Langmuir monolayers containing various lipids. The interactions between AnxA6 and the lipid monolayers were examined by kinetic measurements of the interfacial adsorption and Brewster angle microscopy. We focused on the pH effect on the AnxA6 binding to monolayers containing cholesterol. At acidic pH, AnxA6-1 exhibits the highest affinity to monolayers containing the highest amount of cholesterol. Replacing cholesterol by cholesteryl acetate provided evidence that the hydroxyl group of cholesterol plays a role in AnxA6-lipid interactions. In addition, the affinity of recombinant AnxA6-1 tryptophan mutant (W343F) to the air/water interface and to lipid monolayers was tested. Substitution of Trp343 modified the interfacial properties of the protein and its interactions with sterol monolayers. Our results suggest that the linker region containing Trp343 is important for the interactions between AnxA6-1 and cholesterol. PMID- 20363476 TI - Long-term outcome of combined valve repair and maze procedure for nonrheumatic mitral regurgitation. AB - OBJECTIVE: The long-term outcomes of combined mitral repair and maze procedure for patients with nonrheumatic mitral regurgitation and chronic atrial fibrillation were evaluated. METHODS: Between June 1992 and December 2008, 187 patients underwent a combined mitral repair and maze procedure. The mean follow up period was 7.4 +/- 4.3 years. Chordal reconstruction was performed in 69 patients, leaflet resection in 91, edge-to-edge leaflet suture in 30, and ring annuloplasty in 156. In addition, a cryo-maze procedure was applied in 110, and a Cox-Kosakai maze and radiofrequency maze were applied in the others. RESULTS: There were 2 operative deaths and the 15-year survival was 71%. The 15-year freedom from greater than grade 3 mitral regurgitation was 61%; rates of freedom from heart failure (New York Heart Association class >= III) and reoperations were 79% and 91%, respectively. Cardiac function was improved and left ventricular size was decreased significantly postoperatively. Multivariate analysis showed that a large left ventricular diastolic diameter (>=65 mm) was an independent risk factor for recurrent mitral regurgitation. Eleven thromboembolic episodes (0.79%/patient-year) were detected during follow-up examinations, of which 7 occurred in patients with recurrent atrial fibrillation. Sinus rhythm was regained in 86% after 6 months and in 63% after 15 years. Multivariate analysis showed that a small-voltage f wave was an independent risk factor for AF recurrence. CONCLUSIONS: A combined mitral valve repair and maze procedure provided low rates of morbidity and mortality and led to well-preserved cardiac function. Left ventricular diastolic diameter and f-wave voltage can be accurate predictors of good long-term outcome. PMID- 20363477 TI - Surgical repair of aortopulmonary window associated with interrupted aortic arch: long-term outcomes. PMID- 20363478 TI - Patent ductus arteriosus ligation is associated with impaired left ventricular systolic performance in premature infants weighing less than 1000 g. AB - OBJECTIVE: Patent ductus arteriosus ligation is often complicated by systemic hypotension and oxygenation failure. The ability of the immature myocardium to compensate for altered afterload is poorly understood. The aim of this study was to characterize the effects of patent ductus arteriosus ligation on myocardial performance in preterm infants. METHODS: Serial echocardiographic analysis was performed before and after patent ductus arteriosus ligation. Characteristics of the patent ductus arteriosus, myocardial performance (fractional shortening, mean velocity of circumferential fiber shortening, and left ventricular output) and left ventricular afterload (end-systolic wall stress) were assessed. The stress velocity relationship was measured as a preload-independent, afterload-adjusted measure of myocardial contractility. RESULTS: Forty-six preterm infants were assessed at 28.5 +/- 11.3 days and a weight of 1058 +/- 272 g. Patent ductus arteriosus ligation was followed by increased left ventricular exposed vascular resistance temporally coinciding with reduced left ventricular preload, decreased left ventricular contractility, and low left ventricular output. Neonates weighing 1000 g or less had a higher rate of low fractional shortening (<25%) or low left ventricular output (<170 mL x kg(-1) x h(-1)) and increased need for cardiotropes and demonstrated a trend toward an impaired stress-velocity relationship. Neonates with impaired left ventricular systolic performance were more likely to require cardiotropes and have low systolic arterial pressure, increased heart rate, and abnormal base deficit. CONCLUSION: Patent ductus arteriosus ligation is sometimes associated with impaired left ventricular systolic performance, which is most likely attributable to altered loading conditions. Neonates weighing 1000 g or less are at increased risk of impaired left ventricular systolic performance, which might relate to maturational differences and decreased tolerance to altered loading conditions. PMID- 20363479 TI - Pulmonary autograft valve explants show typical degeneration. AB - OBJECTIVES: We sought to evaluate the microscopic characteristics of pulmonary autograft valve explants. METHODS: Cell density and thickness of the autograft valve ventricularis were determined and compared with those of normal aortic and pulmonary valves (n = 11). Cellular phenotype and extracellular matrix involvement were assessed with immunohistochemistry. Collagen 3-dimensional architecture was studied by means of confocal microscopy. RESULTS: The autograft valve exhibited characteristic thickening of the ventricularis compared with the normal aortic and pulmonary valves (137 vs 77 [P = .058] vs 37 mum [P = .002], respectively). Its cell number was increased compared with those of the normal aortic and pulmonary valves (396 vs 230 [P = .02] vs 303 [P = .083], respectively). Myofibroblasts and stressed endothelial cells, both of which were present in pulmonary autografts, were absent in control valves. The exclusive presence of matrix metalloproteinase 1 was an additional sign of extracellular matrix turnover. Apoptosis, elastinolysis, cell proliferation, and senescence were not expressed. Dense fibrosis of the autograft ventricularis with relatively well-aligned collagen fibers was observed with confocal microscopy. CONCLUSIONS: Fibrous hyperplasia of the ventricularis and cellular and extracellular matrix characteristics of active remodeling were a consistent finding in pulmonary autograft valve explants. The observations suggest a primary valve-related cause to be involved in pulmonary autograft valve failure. PMID- 20363480 TI - Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction. AB - OBJECTIVE: Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. METHODS: Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. RESULTS: Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure volume measurements showed that cardiac function was preserved in these rats. CONCLUSIONS: Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function. PMID- 20363481 TI - Biomechanical implications of the congenital bicuspid aortic valve: a finite element study of aortic root function from in vivo data. AB - OBJECTIVE: Congenital bicuspid aortic valves frequently cause aortic stenosis or regurgitation. Improved understanding of valve and root biomechanics is needed to achieve advancements in surgical repair techniques. By using imaging-derived data, finite element models were developed to quantify aortic valve and root biomechanical alterations associated with bicuspid geometry. METHODS: A dynamic 3 dimensional finite element model of the aortic root with a bicuspid aortic valve (type 1 right/left) was developed. The model's geometry was based on measurements from 2-dimensional magnetic resonance images acquired in 8 normotensive and otherwise healthy subjects with echocardiographically normal function of their bicuspid aortic valves. Numeric results were compared with those obtained from our previous model representing the normal root with a tricuspid aortic valve. The effects of raphe thickening on valve kinematics and stresses were also evaluated. RESULTS: During systole, the bicuspid valve opened asymmetrically compared with the normal valve, resulting in an elliptic shape of its orifice. During diastole, the conjoint cusp occluded a larger proportion of the valve orifice and leaflet bending was altered, although competence was preserved. The bicuspid model presented higher stresses compared with the tricuspid model, particularly in the central basal region of the conjoint cusp (+800%). The presence of a raphe partially reduced stress in this region but increased stress in the other cusp. CONCLUSIONS: Aortic valve function is altered in clinically normally functioning bicuspid aortic valves. Bicuspid geometry per se entails abnormal leaflet stress. The stress location suggests that leaflet stress may play a role in tissue remodeling at the raphe region and in early leaflet degeneration. PMID- 20363482 TI - Infection after implantation of pulsatile mechanical circulatory support devices. AB - OBJECTIVE: INTERMACS is a registry of mechanical circulatory support devices sponsored by the National Institutes of Health. This analysis uses INTERMACS data to define the time course, incidence, and outcome of infection adverse events focusing on the first 3 months after implant. METHODS: Patients entered into INTERMACS from June 23, 2006, to September 30, 2008, were analyzed. Preimplant data (demographics, hemodynamics, and laboratory values), infection adverse events, and other outcomes were recorded. Infection adverse events were analyzed to compare infection rates in subgroups of patients and define risk factors for death. RESULTS: The analysis was confined to pulsatile mechanical circulatory support devices. A total of 593 patients from 88 institutions were entered. Infection was a relatively common event within the first 3 months of implant and was significantly (P = .005) more common in patients with biventricular assist devices than in patients with left ventricular assist devices, although the prevalence of infection equalized in months 4 to 12. Infection had a significant adverse effect on survival. Independent risk factors for death included support with a biventricular assist device, older age, severity of patient illness implantation of the device (INTERMACS level 1), and higher blood urea nitrogen. CONCLUSIONS: Infection remains a relatively frequent adverse event and is associated with decreased survival. Interventions to prevent infection that focus on the preoperative and immediate postoperative periods are the ones most likely to achieve success by diminishing the incidence of infection during the initial 3 months after implantation. Rotary (continuous-flow) pumps are expected to have lower infection rates, but this remains to be seen. PMID- 20363483 TI - Minimally invasive perventricular device closure of perimembranous ventricular septal defect without cardiopulmonary bypass: multicenter experience and mid-term follow-up. AB - OBJECTIVE: To summarize the clinical experiences and mid-term follow-up results of perventricular closure of perimembranous ventricular septal defect without cardiopulmonary bypass under transesophageal echocardiography guidance. METHODS: A total of 408 patients with perimembranous ventricular septal defects, aged 5 months to 15 years (3.1 +/- 1.7 years) with a body weight of 4.5 to 26 kg (13.6 +/- 5.5 kg), underwent perventricular device closure. The procedure was performed via a small lower sternal incision. A guidewire was inserted through the ventricular septal defect to the left ventricle under transesophageal echocardiography guidance after a pursestring suture was placed on the right ventricular free wall. A modified delivery sheath was introduced over the guidewire to establish the delivery pathway. Proper devices were delivered and then deployed if no atrioventricular or aortic valvular disturbance, or residual shunt was detected by transesophageal echocardiography. Patients were followed up with a standard protocol, which is once every month in the first 3 postoperative months and then once every 3 months with echocardiography, electrocardiography, and chest radiography in each follow-up. RESULTS: A total of 393 patients in this group underwent successful closure (96.3%), and the procedure was converted to conventional open repair in 15 patients (3.7%). A total of 213 symmetric devices (54.2%) and 180 asymmetric devices (45.8%) were implanted. Only 6 of the 393 patients (3.5%) received transfusion of blood products. New trivial or mild tricuspid regurgitation was found in 13 patients (3.3%), and there was no worsening of regurgitation in those patients with existing tricuspid regurgitation before operation. Eleven patients (2.8%) had incomplete right bundle branch block. Most of the patients were discharged 3 to 5 days after the operation. Follow-up in all patients ranged from 3 months to 2 years (14.6 +/- 6.2 months) and revealed no residual shunt, new or aggravating aortic regurgitation, obstruction of left or right ventricular outflow tract, or device dislocation. CONCLUSION: Minimally invasive perventricular device closure of ventricular septal defect without cardiopulmonary bypass is a simple, effective, and relatively safe intervention under guidance of transesophageal echocardiography. This method should be considered for patients with ventricular septal defect. Long-term follow-up is necessary. PMID- 20363484 TI - Double-bar application decreases postoperative pain after the Nuss procedure. AB - OBJECTIVE: This biomechanical study aims to elucidate whether additional bar application increases postoperative pain after the Nuss procedure for pectus excavatum. METHODS: Clinical evaluation: The intensity of postoperative pain was compared between patients for whom a single-bar was used (single-bar group: n = 14) and those for whom double bars (double-bar group: n = 10) were used to correct the thoracic deformity. The evaluation was performed by referring to the frequency with which local anesthetics were self-injected in a patient-controlled anesthetic system and how many days were needed for the patients to resume ambulation. Theoretical evaluation: An original simulation system for the Nuss procedure was developed by producing 3-dimensional finite element analysis models from computed tomographic data of patients with pectus excavatum. With this system, single-bar and double-bar placement was simulated separately for the thorax models of the double-bar group. The stresses occurring on the thoraces were then compared between the two situations. RESULTS: Clinical evaluation: Self injection of local anesthetic was more frequent for the single-bar group than for the double-bar group; single-bar patients restarted ambulation later than the double-bar group. Theoretical evaluation: Stresses on the thoraces were smaller when double bars were applied than when a single bar was applied. CONCLUSIONS: Performing double-bar placement decreases postoperative pain. Therefore, surgeons should not hesitate to perform double-bar correction in patients in whom the deformity extends to multiple intercostal spaces, requiring correction of the thorax shape at multiple sites. PMID- 20363485 TI - Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch. AB - OBJECTIVE: Clinical studies have demonstrated the efficacy of oral and intravenous amiodarone therapy to prevent postoperative atrial fibrillation. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. This study addressed the hypothesis that atrium-specific drug delivery through an amiodarone-eluting epicardial patch reduces vulnerability to atrial tachyarrhythmias, whereas ventricular and plasma drug concentrations are minimized. METHODS: Right atrial epicardiums of goats were fitted with electrodes and a bilayered patch (poly[ethylene glycol]-based matrix and poly[lactide-co-caprolactone] backing layer) loaded with amiodarone (10 mg per patch, n = 10) or without drug (n = 6). Electrophysiologic parameters (atrial effective refractory period, conduction time, and rapid atrial response to burst pacing) and amiodarone levels in plasma and tissue were measured during 1 month's follow-up. RESULTS: Epicardial application of amiodarone-eluting patches produced persistently higher drug concentrations in the right atrium than in the left atrium, ventricles, and extracardiac tissues by 2 to 4 orders of magnitude. Atrial effective refractory period and conduction time increased, whereas rapid atrial response inducibility decreased significantly (P < .05) during the 1-month follow-up compared with that seen in animals treated with drug-free patches. Amiodarone concentrations in plasma remained undetectably low (<10 ng/mL). CONCLUSIONS: Atrium-specific drug delivery through an amiodarone-eluting patch produces therapeutic atrial drug concentrations, whereas ventricular and systemic drug levels are minimized. This study demonstrates that sustained targeted drug delivery to a specific heart chamber is feasible and might reduce the risk for ventricular and extracardiac adverse effects. Epicardial application of amiodarone-eluting patches is a promising strategy to prevent postoperative atrial fibrillation. PMID- 20363486 TI - The use of traditional, complementary and alternative medicine in Sri Lankan cancer care: results from a survey of 500 cancer patients. AB - OBJECTIVES: While the introduction of biomedicine within the Sri Lankan healthcare system has resulted in reduced reliance on traditional, complementary and alternative medicine (TCAM) over the last century in Sri Lanka, treatment modalities such as Ayurveda, Sinhala and traditional religious practices still receive considerable public support. Cancer is an increasing burden in Sri Lanka, and whilst Sri Lankans are known to use TCAM for everyday ailments, there has been no research examining the role of TCAM in the context of cancer. The aim of this study was to evaluate the prevalence and patterns of TCAM use by cancer patients. STUDY DESIGN: Cross-sectional survey. METHODS: Data were obtained from two Sri Lankan hospitals using a consecutive convenience sample of 500 cancer patients currently receiving biomedical treatment, over a 10-week period in 2008. RESULTS: Analyses showed that 67.4% of those surveyed used one or more TCAM in conjunction with biomedicine for cancer treatment. The most common were Sinhala, Ayurveda and traditional religious practices. Of those patients who used TCAM, 95.0% gave the main reason for usage as 'they thought it would cure their cancer'. The strongest reason for not using TCAM was on advice from their doctor (80.5%). CONCLUSIONS: The high use of TCAM amongst cancer patients in Sri Lanka raises numerous important issues, including those related to patient safety, potential benefit, interactions with biomedical cancer treatments, and delays in seeking biomedical cancer care. Further research is needed to explore the decision-making processes of cancer patients, including the perceived benefits/limitations of key processes in biomedical and TCAM care. PMID- 20363487 TI - Working towards a reduction in cattle lameness: 1. Understanding barriers to lameness control on dairy farms. AB - On 222 dairy farms, the farmer's perception of the scale of the herd lameness problem was compared with the prevalence detected by observation of the milking herd, and a questionnaire explored the barriers to lameness reduction. Ninety percent of farmers did not perceive lameness to be a major problem on their farm, although the average prevalence of lameness was 36%. For 62% of the sample, lameness was not the top priority for efforts made to improve herd health. Time and labour were important limiting factors for lameness control activities and financial constraints prevented farmers taking action on advice in 30% of cases. Farmers' understanding the implications of lameness for the farm business was limited. Lameness reduction is restricted by farmers' perception of lameness, but also by time, labour and finance; these issues need to be addressed at the industry level to support animal welfare improvement. PMID- 20363488 TI - Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep. AB - Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75*MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 MUg/mL or "shallow" infections caused by bacteria with MICs<0.1 MUg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 MUg/mL. PMID- 20363489 TI - Scale up of diesel oil biodegradation in a baffled roller bioreactor. AB - Diesel oil is a suitable substance to represent petroleum contamination from accidental spills in operating and transportation facilities. Using a microbial culture enriched from a petroleum contaminated soil, biodegradation of diesel oil was carried out in 2.2, 55, and 220 L roller baffled bioreactors. The effects of bioreactor rotation speed (from 5 to 45 rpm) and liquid loading (from 18% to 73% of total volume) on the biodegradation of diesel oil were studied. In the small scale bioreactor (2.2L), the maximum rotation speed of 45 rpm resulted in the highest biodegradation rate with a first order biodegradation kinetic constant of 0.095 d(-1). In the larger scale bioreactors, rotation speed did not affect the biodegradation rate. Liquid loadings higher than 64% resulted in reduced biodegradation rates in the small scale bioreactor; however, in the larger roller bioreactors liquid loading did not affect the biodegradation rate. Biodegradation of diesel oil at 5 rpm and 73% loading is recommended for operating large scale roller baffled bioreactors. Under these conditions, high diesel oil concentrations up to 50 gL(-1) can be bioremediated at a rate of 1.61 gL(-1)d( 1). PMID- 20363490 TI - Investigating the biodegradability of perfluorooctanoic acid. AB - Perfluorooctanoic acid (PFOA) is an industrial chemical that has become disseminated globally in aquatic and terrestrial habitats, humans, and wildlife. Understanding PFOA's biodegradability (susceptibility to microbial metabolic attack) is a crucial element in developing an informed strategy for predicting and managing this compound's environmental fate. Reasoning that PFOA might be susceptible to reductive defluorination by anaerobic microbial communities, we embarked on a 2-phase experimental approach examining the potential of five different microbial communities (from a municipal waste-water treatment plant, industrial site sediment, an agricultural soil, and soils from two fire training areas) to alter PFOA's molecular structure. A series of primarily anaerobic incubations (up to 259d in duration) were established with acetate, lactate, ethanol, and/or hydrogen gas as electron donors and PFOA (at concentrations of 100 ppm and 100 ppb) as the electron acceptor. Cometabolism of PFOA during reductive dechlorination of trichloroethene (TCE) and during reduction of nitrate, iron, sulfate, and methanogenesis were also examined. Endpoints of potential PFOA transformation included release of fluoride and detection of potential transformation products by LC/Orbitrap MS and LC/accurate radioisotope counting in a (14)C radiotracer study. The strongest indication of PFOA transformation occurred during its potential cometabolism at the 100 ppb concentration during reductive dechlorination of TCE. Despite an extensive search for transformation products to corroborate potential cometabolism of PFOA, we were unable to document any alteration of PFOA's chemical structure. We conclude that, under conditions examined, PFOA is microbiologically inert, hence environmentally persistent. PMID- 20363491 TI - Phenotypically directed multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome: a prospective study using UPOINT. AB - OBJECTIVES: Large, controlled trials in chronic pelvic pain syndrome (CPPS) have failed due to patient heterogeneity. To phenotype CPPS patients, we developed the UPOINT system with 6 domains (Urinary, Psychosocial, Organ-Specific, Infection, Neurologic/Systemic and Tenderness). In this study, we treated patients with multimodal therapy based on the UPOINT phenotype and measured response after at least 6 months. METHODS: Patients with CPPS were offered multimodal therapy based on the UPOINT phenotype (eg, Urinary: alpha blocker or antimuscarinic; Organ specific: quercetin; Tenderness: physical therapy). One hundred patients agreed to therapy and were reexamined after 26 weeks. Primary endpoint was a minimum 6 point drop in NIH-Chronic Prostatitis Symptom Index (CPSI). RESULTS: Mean age was 46 years, and median symptom duration was 24 months. A median of 3 UPOINT domains were positive, the most common being Organ-specific (70%), Tenderness (64%), and Urinary (59%). With a median 50-week follow-up, 84% had at least a 6-point fall in CPSI. Number of domains and initial CPSI did not predict response. Mean changes (+/-SD) for CPSI subscores were pain 11.5+/-3.2 to 6.1+/-3.9, urine 4.7+/ 3.1 to 2.6+/-2.0, QOL 9.1+/-2.3 to 4.5+/-2.8, and total 25.2+/-6.1 to 13.2+/-7.2 (all P<.0001). No domain predicted outcome; however, quercetin use resulted in a greater CPSI decrease. CONCLUSIONS: Multimodal therapy using UPOINT leads to significant improvement in symptoms and quality of life. Moreover, a placebo controlled trial for every therapy combination is not feasible, and results using UPOINT compare favorably with all large trials of monotherapy. PMID- 20363492 TI - Spontaneous bladder perforation in a neonate. AB - Spontaneous bladder perforation in the newborn setting is a rare clinical phenomenon that can be life threatening if left untreated. Several risk factors have been identified in previously reported cases such as hypoxia and bladder diverticula. We present the first case of neonatal bladder rupture without any identifiable risk factors. PMID- 20363493 TI - SIU Scholarship: Dr. Noaman Mohammed Almashraki. PMID- 20363494 TI - Impact of laparoscopic inguinal hernia repair mesh on open radical retropubic prostatectomy. AB - OBJECTIVES: Open radical retropubic prostatectomies (RRP) have been abandoned after previous laparoscopic inguinal hernia repair (LIHR) with mesh, which can be a relative contraindication to open RRP. Radiation therapy and radical perineal prostatectomy are alternative treatment options for prostate cancer when faced with this dilemma. Our objective is to report our experience with open RRP after LIHR. METHODS: A retrospective chart review was conducted from January 2000 to December 2007 of all open RRP executed by a single surgeon (F.F.M.) with prior LIHR. All information on LIHR, including laterality and its effect on pelvic lymphadenectomy (LAD), were analyzed. Pre-, intra-, and postoperative data were recorded. RESULTS: Of the 949 men who underwent RRP performed by this surgeon, a cohort of 21 men had prior LIHR (a total of 29 IHR: 13 unilateral and 8 bilateral). The mean age and PSA were 61.0 years and 5.8 ng/mL, respectively. Of the men, 18 and 3 men presented with T1c and T2a clinical stage, respectively. Preoperatively 18 men, 2 men, and 1 man had a Gleason score of 6, 3+4, and 8, respectively. All RRP subsequent to LIHR were successful with minimal complications. A total of 4, 4, 11, and 2 men had stage pT2a, pT2b, pT2c, and pT3a, respectively. Fifteen men (71%) had either unilateral (4 men) or bilateral (11) LAD (all pN0), whereas 6 men had no LAD because of severe pelvic scaring. CONCLUSIONS: Our experience demonstrates that open RRP after LIHR with mesh can typically be performed with minimal risks and in carefully selected patients for best outcomes, but LAD might be compromised. PMID- 20363495 TI - Avagard hand antisepsis vs. traditional scrub in 3600 pediatric urologic procedures. AB - OBJECTIVES: Avagard is a waterless, scrubless, and brushless hand antiseptic approved by the Food and Drug Administration as a replacement for traditional presurgical brush hand scrubbing. We evaluated the use of Avagard compared with hand brush scrub preparation for inpatient and outpatient pediatric urological operations. METHODS: We evaluated the first 1800 patients for whom we used Avagard as a preoperative hand antiseptic and compared them with the last 1800 consecutive patients for whom we performed traditional antiseptic-impregnated hand-brush scrubbing. All patients underwent a variety of inpatient and outpatient open, endoscopic, and laparoscopic pediatric urological procedures. Patients were monitored postoperatively for wound infection, and patients and surgeon were monitored for side effects. A cost analysis was performed. RESULTS: The incidence of wound infection was 2/1800 (0.11%) in the Avagard group and 3/1800 (0.17%) in the hand-scrub group (P > .99 Fisher's exact test). All wound infections were successfully treated with a single course of oral antibiotics. No side effects for the patients or surgeon were noted, including skin irritations or allergic reactions in either group. The traditional hand scrub is nearly 2 times more expensive per application than Avagard. CONCLUSIONS: The incidence of wound infections in pediatric urological procedures is low (0.09%). We observe that Avagard provides comparable hand antisepsis to the traditional surgical scrub in a variety of pediatric urological procedures. Avagard is superior to the surgical hand scrub in cost-effectiveness and time efficiency. Urologists should consider using Avagard for hand antisepsis before surgery. PMID- 20363496 TI - Use of inverted fluoroscope's C-arm during endoscopic treatment of urinary tract obstruction in pregnancy: a practicable solution to cut radiation. AB - OBJECTIVES: To describe the use of pulsed fluoroscopic guidance, to perform endoscopic procedures in pregnant women, by inverting the fluoroscope's c-arm using a lead thyroid collar to shield the fetus from the direct X-ray beam. The use of radiation during treatment of pregnant patients with urolithiasis remains a recurring dilemma. METHODS: Between May 2006 and December 2008, endoscopic treatment due to ureteral stones was attempted in 8 pregnant women. In all cases, we use an inverted fluoroscope's c-arm during endoscopic treatment associated with 2 lead neck thyroid collars to shield the uterus, protecting the fetus from direct radiation. Indication for treatment was symptomatic ureteral stones unresponsive to medical treatment in 7 and persistent fever in 1. RESULTS: Mean ureteral stone size was 8.1+/-4.8 mm, located in the left ureter in 5 (62.5%) cases. Three (37.5%) patients had stone located in the upper ureter, 2 (25%) in the middle ureter, and 3 (37.5) in the distal ureter. In 6 cases, ureteral stones were treated using the semi-rigid ureteroscope, whereas in 1 case a flexible ureteroscope was needed. One woman was treated with insertion of a double-J stent due to associated urinary infection. No women has early delivery related to the endoscopic procedure, and all neonates were perfectly normal. CONCLUSIONS: We present a technique for endoscopic procedures in pregnant women inverting the fluoroscope's c-arm and protecting the fetus from the direct X-ray beam. This practical approach should be specially considered when no portable ultrasound and radiologic assistance in available in the operating room. PMID- 20363497 TI - The effect of heat- or ultra violet ozone-treatment of titanium on complement deposition from human blood plasma. AB - Titanium (Ti) is a well known metallic biomaterial extensively used in dental, orthopaedic-, and occasionally also in blood contacting applications. It integrates well to bone and soft tissues, and is shown upon blood plasma contact to activate the intrinsic pathway of coagulation and bind complement factor 3b. The material properties depend largely on those of the nm-thick dense layer of TiO(2) that becomes rapidly formed upon contact with air and water. The spontaneously formed amorphous Ti-oxide has a pzc approximately 5-6 and its water solubility is at the order of 1-2 micromolar. It is often subjected to chemical- and heat treatments in order to increase the anatase- and rutile crystallinity, to modify the surface topography and to decrease the water solubility. In this work, we prepared sol-gel derived titanium and smooth PVD titanium surfaces, and analysed their oxide and protein deposition properties in human blood plasma before and after annealing at 100-500 degrees C or upon UVO-treatment for up to 96 hours. The blood plasma results show that complement deposition vanished irreversibly after heat treatment at 250-300 degrees C for 30 minutes or after UVO exposure for 24 hours or longer. XPS and infrared spectroscopy indicated change of surface water/hydroxyl binding upon the heat- and UVO treatments, and increased Ti oxidation. XRD analysis confirmed an increased crystallinity and both control (untreated) and annealed smooth titanium displayed low XRD-signals indicating some nanocrystallinity, with predominantly anatase phase. The current results show that the behaviour of titanium dioxide in blood contact can be controlled through relatively simple means, such as mild heating and illumination in UV-light, which both likely irreversibly change the stoichiometry and structure of the outmost layers of titanium dioxide and its OH/H(2)O binding characteristics. PMID- 20363498 TI - TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2+) influx. AB - Ion channels are involved in various physiologic and pathologic processes, including the migration of tumor cells that is required for metastasis. To determine whether transient receptor potential melastatin 7 (TRPM7) Ca(2+) channels play an important role in the migration of tumor cells, we examined the potential function of TRPM7 channels in the migration of 5-8F and 6-10B human nasopharyngeal carcinoma cells. The migratory potential of 5-8F cells was significantly decreased by extracellular Ca(2+) chelator (EGTA), TRPM7 inhibitors (La(3+), 2-APB), or TRPM7 knockdown. Conversely, the addition of TRPM7 activator Bradykinin and overexpression of TRPM7 promoted the migration of 5-8F and 6-10B cells. Furthermore, the sustained Ca(2+) influx regulated by TRPM7 activated release of Ca(2+) stores via ryanodine receptors by a calcium-induced calcium release (CICR) mechanism. This study suggests, first, that Ca(2+) influx is required for the migration of human nasopharyngeal carcinoma 5-8F cells. Second, and more importantly, it identifies TRPM7 as a novel potential-regulator of the Ca(2+) influx that allows migration of 5-8F cells. TRPM7, therefore, might have potential as a prognostic indicator and as a therapeutic target in nasopharyngeal carcinoma. PMID- 20363499 TI - Hyperlipidemia in a myeloma patient after bortezomib treatment. PMID- 20363500 TI - Speciation and evaluation of Arsenic in surface water and groundwater samples: a multivariate case study. AB - The principal object of the current study was to estimate total arsenic and its inorganic speciation in different origins of surface water (n=480) and groundwater (n=240) of Sindh, Pakistan. This study provided a description based on the evaluation of physico-chemical parameters of collected water samples and possible distribution of As with respect to its speciation. The concentration of total inorganic As (iAs) and its species (As(3+) and As(5+)) for the surface and underground water was reported in terms of basic statistical parameters, principal component analysis, cluster analysis, metal-to-metal correlations and linear regression analyses. The chemical correlations were observed by PCA, which were used to classify the samples by CA, based on the PCA scores. Standard addition method confirmed the accuracy; the recoveries of As(3+) and iAs were found to be >98%. The concentration of As(5+) in the water samples was calculated by the difference of the total inorganic arsenic and As(3+). The results revealed that the groundwater of the understudied area was more contaminated as compared to the surface water samples. The mean concentration of As(3+) and As(5+) in the surface water and groundwater samples were in the range 3.0 to 18.3 and 8.74-352 microg/L, respectively. PMID- 20363501 TI - Interactive effects of Cr and Fe treatments on plants growth, nutrition and oxidative status in Zea mays L. AB - The effects of Cr and Fe, singly and in combination were investigated on nutrients uptake (Cu, Zn and Mn), lipid peroxidation, antioxidant enzymes, chlorophyll content and growth parameters in Zea mays L. var. Ruchi (SRHM 445). Roots of the Cr treated plants were stunted and root hair formation was greatly impaired. The leaves were bearing wilted appearance. Cr was primarily accumulated in the roots with a low translocation rate to the leaves. Cu absorption decreased with increase in Cr concentrations only in roots. In leaves there is no correlation. Iron induced lipid peroxidation was higher in the leaves at both the concentrations (3 and 9 microg ml(-1)) after 7d, and decreased significantly by the addition of Cr. Concentrations of most leaves antioxidants were lower in mixed metal treatment compared to single treatments, indicating an interaction between metals leading to reduced cellular effects as indicated by lower lipid peroxidation levels. Changes in APX and GPX activities observed in the leaves of contaminated-plants suggest their involvement in heavy-metal stress tolerance. The plant seems to be tolerant as the translocation of Cr was recorded less, which decreased in the presence of Fe. PMID- 20363502 TI - Risk of cataract development among children with juvenile idiopathic arthritis related uveitis treated with topical corticosteroids. AB - PURPOSE: We sought to investigate the risk of cataract development among patients with juvenile idiopathic arthritis (JIA)-associated uveitis treated with topical corticosteroids. DESIGN: Retrospective cohort study. PARTICIPANTS: We included 75 patients with JIA-associated uveitis observed from July 1984 through August 2005 at a single academic center. METHODS: Clinical data on these patients were collected by chart review and were analyzed. MAIN OUTCOME MEASURES: Incidence of new-onset cataract. Risk factors for cataract development were assessed with attention paid to the use of topical corticosteroids. RESULTS: Over a median follow-up of 4 years, the incidence of new-onset cataract was 0.04/eye-year (EY; 95% confidence interval [CI], 0.02-0.09). Of the 60 eyes in 40 patients who received topical corticosteroid therapy, there was a dose-dependent increase in the rate of cataract development among eyes receiving topical corticosteroids. The incidence of cataract was 0.01/EY for eyes treated with < or = 3 drops daily and 0.16/EY (P = 0.0006 for log-rank test) for eyes treated with >3 drops daily. Among eyes receiving < or = 2 drops daily, the incidence of cataract was 0/EY (95% CI [1 sided], 0.03/EY). Presence of posterior synechiae, active uveitis, and use of topical corticosteroids at presentation were significantly associated with cataract development after controlling for confounding variables. Use of topical corticosteroids was associated with cataract formation independent of uveitis activity. Using longitudinal data analysis and controlling for duration of uveitis, presence and degree of active uveitis, and concomitant use of other forms of corticosteroids in a time-updated fashion, treatment with < or = 3 drops daily of topical corticosteroid was associated with an 87% lower risk of cataract formation compared with eyes treated with >3 drops daily (relative risk, 0.13; 95% CI, 0.02-0.69; P = 0.02). CONCLUSIONS: In our cohort, topical corticosteroid use was associated with an increased risk of cataract formation independent of active uveitis or presence of posterior synechiae. However, chronic use of topical corticosteroids dosed at < or = 3 drops daily seemed to be associated with a lower risk of cataract development relative to eyes receiving higher doses over follow-up in the setting of suppressed uveitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 20363503 TI - Long-term changes in posterior chamber phakic intraocular collamer lens vaulting in myopic patients. AB - OBJECTIVE: Evaluation of central and midperipheral vaulting of the posterior chamber phakic intraocular Collamer lens (ICL; Staar Surgical Inc., Monrovia, CA) in eyes with moderate to high myopia. DESIGN: Retrospective analysis of prospectively collected data. PARTICIPANTS: Eighty-four eyes treated with the latest ICL (V4 model) and 27 eyes treated with early ICL models were examined. METHODS: After standardized ICL implantation, patients underwent complete ophthalmologic examinations before surgery and at 1 week, 1 month, 3 months, 6 months, and at yearly intervals thereafter. Central vaulting was measured using the Jaeger device (Haag-Streit, Bern, Switzerland). From 2006 onward, vaulting was measured additionally by optical coherence tomography (Visante OCT; Carl Zeiss Meditec, Jena, Germany). Using the Visante OCT, the crystalline lens rise and the midperipheral vaulting of the ICL were assessed. MAIN OUTCOME MEASURES: Central vaulting after ICL implantation. RESULTS: The mean duration of follow-up was 74.1+/-23.1 months and 96.3+/-50.2 months in eyes treated with V4 and early models, respectively. Postoperative central vaulting was 466+/-218 microm (range, 30-900 microm) in eyes treated with the V4 models and 321+/-200 microm (range, 150-900 microm) in those treated with early ICL models. From the 6-month follow up onward, a continuous and nearly linear reduction of central vaulting was observed. At the 10-year follow-up, the mean central vaulting was reduced to 184+/-159 microm (range, 6-500 microm) and 138+/-218 microm (range, 0-820 microm) in eyes treated with V4 or early models, respectively. Eyes with total vaulting had a mean central vaulting of 407+/-202 microm (range, 180-730 microm), whereas those with midperipheral contact had a significantly lower central vaulting of 105+/-87 microm (range, 0-200 microm). CONCLUSIONS: This study revealed consistent reduction of central vaulting over a 10-year period and provides further evidence that insufficient vaulting of the ICL is responsible for the development of anterior subcapsular cataract. A minimum central vaulting of 230 microm seems to be necessary to ensure total vaulting of the ICL. If an ICL is chosen for the correction of myopia, targeting for the greatest possible postoperative central vaulting is advised to achieve safe and complete vaulting for several years. PMID- 20363504 TI - Corneal shape changes after 2.0-mm or 3.0-mm clear corneal versus scleral tunnel incision cataract surgery. AB - PURPOSE: To compare changes in corneal shape and in regular and irregular corneal astigmatism after 3.0- or 2.0-mm clear corneal incision cataract surgery (CICS) with those occurring after 3.0- or 2.0-mm scleral incision cataract surgery (SICS). DESIGN: Randomized, comparative clinical trials. PARTICIPANTS: Ninety patients scheduled for bilateral cataract surgery were randomized to 1 of 2 groups: 3.0- or 2.0-mm CICS in the left eye and 3.0- or 2.0-mm SICS in the right eye or CICS in the right eye and SICS in the left eye. INTERVENTION: All patients underwent CICS and SICS at the 9-o'clock meridian in fellow eyes. MAIN OUTCOME MEASURES: Induced corneal astigmatism was determined using vector analysis, and the averaged changes in corneal shape and irregular astigmatism were examined using videokeratography before surgery and at 2 days and 1, 2, 4, and 8 weeks after surgery. RESULTS: For the 3.0-mm incision, induced astigmatism was significantly greater in the CICS group than in the SICS group (P < or = 0.0329) at 2 weeks and later. The average of difference map on videokeratography in the CICS group showed a marked wound-related flattening and coupled steepening around the flattened area at 2 days after surgery, and these changes persisted for up to 8 weeks: the changes were markedly less in the SICS group. Among the irregular astigmatic components, higher-order irregularity in the CICS group was greater than that in the SICS group (P<0.0001). For the 2.0-mm incision, no significant difference was found between the CICS and SICS groups in induced astigmatism or in irregular astigmatic components. The average of difference map of the CICS group showed a slight wound-related flattening around the incision at 2 days after surgery, but this decreased by 2 weeks; the map of the SICS group showed little change. CONCLUSIONS: Changes in corneal astigmatism and shape after 2.0-mm CICS are virtually the same as those after 2.0-mm SICS, whereas those occurring after 3.0-mm CICS are significantly greater than those occurring after 3.0-mm SICS, which suggests that CICS is suitable for microincision cataract surgery. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20363505 TI - A proposed method of logarithmic transformation of optical coherence tomography data for use in clinical research. AB - PURPOSE: To evaluate a logarithmic transformation of retinal thickness measurements from optical coherence tomography as a new approach to assess clinically meaningful changes in retinal thickness. DESIGN: Methodologic, evidence-based review. METHODS: Standard published approaches for assessing change in retinal thickness over time, as measured by optical coherence tomography (OCT), were compared with a new approach based on a logarithmic transformation of the retinal thickness data. Comparative examples were derived using published data from a clinical trial comparing intravitreal corticosteroid injections for diabetic macular edema with standard laser treatment. MAIN OUTCOME MEASURES: Comparative examples using Diabetic Retinopathy Clinical Research Network data. RESULTS: Logarithmic transformation of retinal thickness data results in a more normalized distribution of OCT data and allows for data analyses assessing proportionate changes in retinal thickness during follow-up. CONCLUSIONS: For analysis of grouped data, a logarithmic transformation of the OCT retinal thickness measurements (logOCT) provides several analytic advantages. Distributions of retinal thickness in groups of eyes with diabetic macular edema, and many other causes of macular thickening, tend to be skewed to the right; the logOCT transformation tends to normalize these distributions, which has value for statistical comparisons. For assessing whether the observed OCT change in a patient is real (and not due to testing variability), a 1-step log scale change exceeds the measurement error for all degrees of retinal thickness in current instruments. In addition, this log scale is similar to the logarithm of the minimum angle of resolution (logMAR) scale used for visual acuity. Steps on the log scale for change in thickness seem to be better related to clinical importance than the actual change in microns because each step on the log scale is the same proportionate change in thickness, with a 3-step change equaling a halving or doubling of thickness, regardless of the baseline value. Transformation of OCT retinal thickness data to logOCT may assist in the assessment of clinically meaningful changes in retinal thickness just as use of the logMAR scale has helped to assess clinically meaningful changes in visual acuity. PMID- 20363506 TI - Genome-wide association study of normal tension glaucoma: common variants in SRBD1 and ELOVL5 contribute to disease susceptibility. AB - PURPOSE: Factors contributing to the development of normal tension glaucoma (NTG), degenerative optic neuropathy characterized by the progressive loss of retinal ganglion cells, optic nerve axons, and visual fields, have not been determined. To identify genetic risk factors for NTG, we performed a genome-wide association study of NTG. DESIGN: Case-control study. PARTICIPANTS: The study cohort consisted of 305 Japanese patients with NTG and 355 controls. METHODS: We genotyped 500,568 single-nucleotide polymorphisms (SNPs) and assessed the allelic diversity among cases and controls. MAIN OUTCOME MEASURES: Genotypes of 500,568 SNPs. RESULTS: The 2 most strongly NTG-associated SNPs, rs3213787 and rs735860, are located in an intron of SRBD1 and the 3'-untranslated region of ELOVL5 (P = 2.5 x 10(-9), odds ratio = 2.80 and P = 4.1 x 10(-6), odds ratio = 1.69), respectively. Real-time quantitative reverse transcription-polymerase chain reaction assays showed significantly increased expression of each gene in the white blood cells of subjects harboring the risk allele of these SNPs. CONCLUSIONS: Our genome-wide association study identified SRBD1 and ELOVL5 as new susceptibility genes for NTG. Because SRBD1 and ELOVL5 are reportedly involved in the induction of cell growth inhibition or apoptosis, the regulation of SRBD1 and ELOVL5 cascades may play an important physiologic role in the risk of NTG development. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20363507 TI - Natural history of radiation papillopathy after proton beam irradiation of parapapillary melanoma. AB - PURPOSE: To evaluate the natural history of radiation papillopathy after proton beam irradiation of parapapillary choroidal melanoma. DESIGN: Noncomparative case series. PARTICIPANTS: Ninety-three eyes of 93 patients. METHODS: Retrospective chart review of patients with choroidal melanoma within 0 to 1 disc diameter (DD) of the optic nerve and at least 2 DD away from the fovea treated with proton beam irradiation. MAIN OUTCOME MEASURES: Rates of papillopathy, visual loss, and visual improvement. RESULTS: Sixty-eight percent of patients developed papillopathy a median of 1.5 years (17.7 months) after radiation. Among patients who developed papillopathy, 5-year rates of vision retention were 42% for counting fingers or better and 23% for 20/200 or better. At 5 years after the onset of papillopathy, 31% of patients had spontaneous visual improvement of 3 or more lines compared with the time of papillopathy diagnosis. CONCLUSIONS: Even in eyes receiving high doses of radiation to the optic nerve for treatment of intraocular tumors, approximately two thirds of patients develop radiation papillopathy. After the development of papillopathy, 42% of eyes retain useful vision and one third of eyes have significant spontaneous visual improvement over 5 years. The natural history of radiation papillopathy may be more favorable than previously assumed, and therefore treatments for this condition must be compared with an appropriate control group. PMID- 20363508 TI - Assessment of risk factors for infantile cataracts using a case-control study: National Birth Defects Prevention Study, 2000-2004. AB - OBJECTIVE: To identify risk factors for infantile cataracts of unknown etiology. DESIGN: Case-control study. PARTICIPANTS: Case infants (n = 152) and control infants (n = 4205) enrolled in the National Birth Defects Prevention Study for birth years 2000-2004. METHODS: Multivariate analysis was performed exploring associations for risk factors for bilateral and unilateral infantile cataracts of unknown etiology. MAIN OUTCOME MEASURES: Infantile cataracts of unknown etiology. RESULTS: Maternal interviews were completed for 43 case infants with bilateral and 109 with unilateral infantile cataracts of unknown etiology. Very low birth weight (<1500 g) was associated with both unilateral (adjusted odds ratio [OR], 6.0; 95% confidence interval [CI], 2.2-16.3) and bilateral (OR, 13.2; 95% CI, 4.2 41.1) cataracts, whereas low birth weight (1500-2499 g) was only associated with bilateral cataracts (OR, 3.3; 95% CI, 1.3-8.1). Infants with unilateral cataracts were more likely to be born to primigravid women (OR, 1.6; 95% CI, 1.0-2.7) than women with > or =2 previous pregnancies, although this was of borderline significance. Although not significant, effect estimates were elevated suggesting a possible association between unilateral cataracts and maternal substance abuse during pregnancy, and between bilateral cataracts and urinary tract infection during pregnancy and aspirin use during pregnancy. CONCLUSIONS: Very low birth weight is associated with both bilateral and unilateral cataracts, whereas low birth weight is associated with bilateral cataracts and primigravidity with unilateral cataracts. Other associations, although not statistically significant, suggest risk factors that merit further research. PMID- 20363509 TI - Cervical vascular and upper airway asymmetry in Velo-cardio-facial syndrome: correlation of nasopharyngoscopy with MRA. AB - PURPOSE: Velo-cardio-facial syndrome (VCFS), the most common genetic syndrome causing cleft palate, is associated with internal carotid and vertebral artery anomalies, as well as upper airway asymmetry. Medially displaced internal carotid arteries, often immediately submucosal, present a risk of vascular injury during pharyngeal flap surgery for velopharyngeal insufficiency (VPI). We evaluate the frequency and spectrum of cervical vascular anomalies in a large cohort of VCFS patients correlating MRA with nasopharyngolaryngoscopy in detecting at risk carotid arteries. Furthermore, we assess the relationship with respect to laterality between cervical vascular patterns and the asymmetric abnormalities of these subjects' upper airways. METHODS: Cervical MRAs of 86 subjects with VCFS and 50 control subjects were independently reviewed by three neuroradiologists. The course of the internal carotid and vertebral arteries was identified within the pharyngeal soft tissues. Medial deviation, level of bifurcation, dominance, anomalous origin, and vessel tortuosity were recorded. Nasopharyngoscopy examinations were available for retrospective review in 43 patients and were assessed for palatal and posterior pharyngeal wall symmetry, true vocal cord motion and size, and for the presence or absence of carotid pulsations. The endoscopic findings were compared with MRA results. RESULTS: Of the 86 subjects, 80 (93%) had one or more vascular anomalies. 42 subjects (49%) were found to have medial deviation of at least one internal carotid artery. In 24 subjects (28%) the anomalous internal carotid artery was directly submucosal; four of these were bilateral (5% of the total sample, 17% of those with a submucosal internal carotid). Other carotid anomalies included low carotid bifurcation (44 subjects or 51%), anomalous origin of the right common carotid (32 cases, or 37%), and two cases of internal carotid agenesis/hypoplasia. Vertebral artery anomalies included vessel tortuosity (34 cases, or 40%), hypoplasia (10 cases, or 12%), looping (4 cases, or 5%), and one case of a double left vertebral artery. Though patients in our study showed an asymmetric distribution of vascular anomalies, no association was found between the laterality of palatal motion, pharyngeal fullness, or laryngeal movement and structure with ipsilateral vertebral or carotid artery anomalies. Of the 33 pulsatile carotid arteries visualized at nasopharyngoscopy, only nine were found to be submucosal on MRA. In contrast, 11 submucosal carotid arteries confirmed at MRA demonstrated no visible pulsations. Positive and negative predictive values of pulsative arteries seen endoscopically for MRA confirmation of a submucosal carotid course was 27% and 79% respectively. CONCLUSIONS: Carotid and vertebral artery anomalies are common in VCFS including marked medial deviation of the internal carotid artery in close proximity to the donor site for pharyngeal flap surgery. Lack of correlation between laterality of vascular anomalies and upper airway structural asymmetry in VCFS does not support the hypothesis that palatal, pharyngeal, and laryngeal anomalies are due to secondary developmental sequences caused by in utero vascular insufficiency. The presence or absence of carotid pulsations seen by nasopharyngoscopy does not correlate with the carotid arterial depth identified on MRA. Furthermore, identification of the relative medial-lateral retropharyngeal position of a submucosal carotid affords the opportunity to modify the surgical approach. These findings further support the routine use of pre-operative neck MRA in VCFS patients in surgical planning. PMID- 20363510 TI - Impact of oseltamivir treatment on the incidence and course of acute otitis media in children with influenza. AB - OBJECTIVE: Acute otitis media (AOM) is the most common complication of pediatric influenza, and imposes a substantial health care burden. We examined the influence of oseltamivir treatment on the incidence and course of AOM in children with influenza. METHODS: In the original study, 695 children 1-12 years who presented within 48h of the onset of influenza-like symptoms were randomized to oseltamivir (2mg/kg) or placebo given twice daily for 5 days. AOM was assessed at enrollment and days 3, 6 (+/-1), 10 (+/-2) and 28 (+/-7). AOM was clinically diagnosed by the participating primary care provider, supported by tympanometry when possible. We performed a retrospective analysis of those participants with laboratory-confirmed influenza (LCI). Assessments included the incidence and clinical course of new AOM cases. RESULTS: In all, 452 children had LCI; 217 received oseltamivir and 235 placebo. AOM was diagnosed on or after study day 3 at a significantly lower frequency in the oseltamivir versus placebo group (12.4% versus 21.7%; relative risk [RR]: 0.57 [95% CI: 0.37, 0.88], respectively). Treatment effects were greatest for children 1-2 years (RR=0.42 [95% CI: 0.20, 0.89]) and 3-5 years (RR=0.45 [95% CI: 0.19, 1.04]), in whom the incidence of AOM was highest. CONCLUSIONS: Oseltamivir treatment significantly reduces the emergence of new AOM infections in children with LCI; effects are most pronounced in those <5 years. CLINICAL TRIAL NUMBER: WV15758. PMID- 20363511 TI - Changes in vertical dentofacial morphology after adeno-/tonsillectomy during deciduous and mixed dentitions mouth breathing children--1 year follow-up study. AB - OBJECTIVE: The aim of this 1 year follow-up study was to investigate, in mouth breathing children, the impact of respiration normalization on vertical dentofacial growth during two stages of dental development after adeno /tonsillectomy. METHOD: Linear and angular cephalometric measurements, as well as tracing superimposition of serial lateral cephalograms of 39 patients in the treatment group were compared with those of 31 untreated mouth breathing controls. Cephalometric records in the treatment group comprised registrations made at baseline before surgery (T(0)), and then at approximately 1 year post operatively (T(1)). Corresponding registrations were available for the control group, with a baseline cephalometric radiograph taken approximately 1 year before the second one (T(0) and T(1), respectively). Treatment and untreated groups were divided into deciduous and mixed dentition groups to aid the identification of an optimum timing for normalizing the respiration after T&A, under a vertical dentofacial perspective. RESULTS: After 1 year of follow up, no statistically significant difference on vertical dentofacial growth was observed in deciduous or mixed dentitions treatment groups compared to the same occlusal developmental stage of untreated control groups. CONCLUSION: The results indicate that regarding the vertical dentofacial growth pattern normalization of the mode of respiration after T&A in young children (deciduous dentition) is not more effective than in older children (mixed dentition). PMID- 20363512 TI - Primary pediatric endonasal dacryocystorhinostomy--a review of 58 procedures. AB - OBJECTIVES: The objectives of this study are to report the outcomes of pediatric patients with lacrimal system obstruction who underwent primary endoscopic dacryocystorhinostomy (EDCR). STUDY DESIGN: The authors conducted a retrospective noncomparative case series. METHODS: The operative and postoperative data have been collected in 58 children aged between 3 months and 13 years (mean 4.1 years). The total of 58 primary EDCRs has been performed by two surgeons using a standardized surgical technique. The EDCRs were performed 52 times on one eye, 6 times on both eyes (3 times simultaneously, 3 times at the separate sitting with an interval of 4-6 months). The follow-up evaluations include taking history, clinical examinations including a fluorescein disappearance test. RESULTS: The follow-up interval ranged from 12 to 36 months (mean 17 months, median 15 months). The success rate was 51/58 (87.9%) in all 58 EDCRs. The success rate was 47/51 (92.2%) in the group of postsaccal obstructions, 3/5 (60.0%) in the group of postsaccal and suprasaccal obstrutcions and 1/2 (50.0%) in presaccal obstructions. The procedures were successful in all eight children aged under 1 year old (100%) and in 14 of 15 children between 1 and 2 years old (93.3%). The silicone intubation was used in 54 EDCRs. CONCLUSIONS: The endoscopic DCR is a safe and effective procedure for most children with the success rate comparable to that achieved in the external DCR and in adults. The success rate of the postsaccal obstructions is significantly higher than in presaccal or combined pre and postsaccal obstructions. PMID- 20363513 TI - CHARGE: an association or a syndrome? AB - INTRODUCTION: CHARGE "association" is a rare clinical entity with multiple congenital anomalies that necessitates a multidisciplinary approach. Its diagnosis is important not only for the pediatric surgery practice but also for the otorhinolaryngology practice as it complicates with a number of major surgical anomalies. The aim of this paper is to present the latest evidences on the genetic basis of the disease. MATERIALS AND METHODS: In order to evaluate, a computed literature review was undertaken using PubMed and OMIM databases. RESULTS: Heterozygous mutations within the chromodomain helicase DNA binding protein 7 (CHD7) were reported in every two of three CHARGE patients. CHD protein family is located on chromosome 8q11.2 and is known to regulate chromatin remodeling which plays an essential role in the developmental gene expression. That is why the haploinsufficiency of CHD7 gene due to heterozygous mutations results in not only the postnatal but also the prenatal developmental regulation errors. The wide expression of this gene in the prenatal period overlaps with the broad spectrum of the phenotypic symptoms of the disease. CONCLUSION: CHD7 gene haploinsufficiency is expected to be the underlying basis of CHARGE. Even though the genetic basis is unsolved in one-third of the patients, the current evidence supports the term "syndrome" rather than an "association" should be more appropriate for CHARGE. PMID- 20363514 TI - The odyssey of marine pharmaceuticals: a current pipeline perspective. AB - The global marine pharmaceutical pipeline consists of three Food and Drug Administration (FDA) approved drugs, one EU registered drug, 13 natural products (or derivatives thereof) in different phases of the clinical pipeline and a large number of marine chemicals in the preclinical pipeline. In the United States there are three FDA approved marine-derived drugs, namely cytarabine (Cytosar U((R)), Depocyt((R))), vidarabine (Vira-A((R))) and ziconotide (Prialt((R))). The current clinical pipeline includes 13 marine-derived compounds that are either in Phase I, Phase II or Phase III clinical trials. Several key Phase III studies are ongoing and there are seven marine-derived compounds now in Phase II trials. The preclinical pipeline continues to supply several hundred novel marine compounds every year and those continue to feed the clinical pipeline with potentially valuable compounds. From a global perspective the marine pharmaceutical pipeline remains very active, and now has sufficient momentum to deliver several additional compounds to the marketplace in the near future; this review provides a current view of the pipeline. PMID- 20363515 TI - Influence of ovarian stage on transcript profiles in fathead minnow (Pimephales promelas) ovary tissue. AB - Interpretation of toxicogenomic experiments conducted with ovary tissue from asynchronous-spawning small fish species is complicated by background variation in the relative abundance and proportion of follicles at different stages within the ovary tissue sample. This study employed both real-time quantitative polymerase chain reaction and a 15,000 gene oligonucleotide microarray to examine variation in the fathead minnow (Pimephales promelas) ovarian transcriptional profile as a function of quantitative and qualitative differences in ovarian histology. The objectives were to provide data that could potentially aid interpretation of future toxicogenomics experiments, identify putative stage related transcriptional markers, and generate insights into basic biological regulation of asynchronous oocyte development. Multiple lines of evidence from the present study indicate that variation in the transcriptional profile is primarily dependent on the relative abundance of previtellogenic versus vitellogenic follicles in the ovary. Due to the relatively small proportions of mature ovulated follicles or atretic follicles in the overall follicle population, few potential transcriptional markers of maturation, ovulation, or atresia could be identified. However, among the 460 differentially expressed genes identified in the present study, several targets, including HtrA serine peptidase 3 (htra3), tissue inhibitor of metalloproteinase 3 (timp3), aquaporin 8 (aqp8), transgelin 2 like (tagln2), Nedd4 family interacting protein 2 (ndfip2), chemokine ligand 12a (cxcl12a), midkine-related growth factor (mdka), and jagged 1b (jag 1b) exhibited responses and functional properties that support them as candidate molecular markers of significant shift in gross ovarian stage. Genes associated with a diversity of functions including cellular development, morphogenesis, coated vesicle transport, sexual reproduction, and neuron development, among others, were statistically enriched within the list of 460 genes differentially expressed among different ovarian classes. Overall, results of this study provide insights into background variation in ovary transcript profiles that should aid and enhance the interpretation of toxicogenomic data generated in experiments conducted with small, asynchronous-spawning fish species. PMID- 20363516 TI - Embryonic gene expression among pollutant resistant and sensitive Fundulus heteroclitus populations. AB - Changes in gene expression, coupled with biochemical, physiological, and behavioral alterations, play a critical role in adaptation to environmental stress. Our goal was to explore ways natural populations may have adapted to local, polluted environments. We took advantage of natural populations of Fundulus heteroclitus, one of the few studied fish species in North America that has established resistant populations in highly contaminated urban estuaries. We analyzed morphology, physiology, and gene expression of developing F. heteroclitus embryos during late organogenesis (stage 31); these embryos were from both resistant and sensitive populations and were raised in a common, unpolluted environment. While cardiac heart rates show significant differences between embryos of parents from clean and heavily contaminated Superfund sites, time-to-stage, embryo morphology, and gene expression profile analyses do not differ significantly between untreated embryos from resistant and sensitive populations. Further evaluation that includes tissue-specific approaches in gene expression analysis and larger sample sizes may be necessary to highlight important phenotypes associated with mechanisms of sensitivity and resistance among natural F. heteroclitus embryo populations. Alternatively, population differences may be masked by developmental canalization, and biologically important differences between sensitive and resistant embryos may only manifest with exposure (e.g., be dependent on gene by environment interactions). PMID- 20363517 TI - Effects of exposure to sublethal propiconazole on the antioxidant defense system and Na+-K+-ATPase activity in brain of rainbow trout, Oncorhynchus mykiss. AB - Propiconazole (PCZ), a triazole fungicide, is widely present in the aquatic environment, but little is known regarding its chronic toxicity in the fish brain. This study assessed the effects of long-term exposure to PCZ on the antioxidant defense system and Na(+)-K(+)-ATPase activity of rainbow trout brain. Fish were exposed to sublethal concentrations of PCZ (0.2, 50, and 500 microg/l) for 7, 20, and 30 days, respectively. Oxidative stress indices (reactive oxygen species, lipid peroxidation, and carbonyl protein) and antioxidant parameters (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and reduced glutathione) were measured, as well as Na(+)-K(+)-ATPase activity. Adaptive responses to PCZ-induced stress were observed at 7 days. With prolonged exposure, significantly higher levels of oxidative indices were indicative of oxidative stress, as also were the significant inhibition of antioxidant enzyme activity and reduced glutathione content. Na(+)-K(+)-ATPase activity was significantly inhibited after prolonged exposure. Chemometrics of all parameters by principal component analysis, enabled the separation of sampled individuals into four groups with 93.39% of total accumulated variance. A low level of oxidative stress can induce the adaptive responses of the antioxidant defense system, while prolonged exposure to PCZ may lead to serious oxidative damage in fish brain. We suggest that selected biochemical markers in fish brain could be used as potential biomarkers for monitoring residual fungicides present in the aquatic environments. PMID- 20363518 TI - Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count. AB - BACKGROUND: 22q11.2 deletion syndrome is common affecting nearly 1 in 3000, including many with DiGeorge Syndrome and 5% of individuals with congenital heart disease. Diagnosis is important because affected patients have impaired immune function and may suffer high mortality rates if given non-irradiated blood products from graft versus host disease. Symptomatic hypocalcaemia may also occur. Our objective was to determine whether mean platelet volume (MPV), available from the routine full blood count, may be a useful and rapid indicator of 22q11.2 deletion. METHOD: A retrospective case control cohort study analysing MPV and 22q11.2 deletion status was performed in a paediatric population (n = 166) undergoing cardiac surgery between 1999 and 2005. RESULTS: Twenty children were 22q11.2 positive. The median MPV was significantly larger for the 22q11.2 positive patient group compared to the non-22q11.2 patients (10.9fL versus 8.6fL, p<0.001). The area under the curve of the receiver operating characteristics (ROC) curve of MPV was large enough (0.85) to enable the accurate prediction of 22q11.2 deletion using MPV. CONCLUSIONS: MPV is a useful screening test, involving no extra laboratory work, cost or patient discomfort. MPV>10fL is a positive predictor of the presence of 22q11.2 deletion in children with congenital heart disease (specificity 89.7%). This finding should aid rapid decision-making for ordering irradiated blood products to prevent potentially fatal transfusion-associated graft versus host disease. It will alert clinicians to monitor serum calcium levels closely to prevent hypocalcaemic seizures. PMID- 20363519 TI - The effect of Medicare coverage for the disabled on the market for private insurance. AB - We investigate whether the removal of high-cost individuals from private insurance markets leads to greater coverage for individuals who are similar but not as high cost. Using data on insurance coverage from the Panel Study of Income Dynamics, we estimate the effect of the extension of Medicare to the disabled on the private insurance coverage of non-disabled individuals. We find that the insurance coverage of individuals who had a health condition that limited their ability to work increased significantly in states with high versus low rates of disability. PMID- 20363520 TI - An economic evaluation of the war on cancer. AB - For decades, the US public and private sectors have committed substantial resources towards cancer research, but the societal payoff has not been well understood. We quantify the value of recent gains in cancer survival, and analyze the distribution of value among various stakeholders. Between 1988 and 2000, life expectancy for cancer patients increased by roughly four years, and the average willingness-to-pay for these survival gains was roughly $322,000. Improvements in cancer survival during this period created 23 million additional life-years and roughly $1.9 trillion of additional social value, implying that the average life year was worth approximately $82,000 to its recipient. Health care providers and pharmaceutical companies appropriated 5-19% of this total, with the rest accruing to patients. The share of value flowing to patients has been rising over time. In terms of economic rates of return, R&D investments against cancer have been a success, particularly from the patient's point of view. PMID- 20363521 TI - Visceral fat is negatively associated with B-type natriuretic peptide levels in patients with advanced type 2 diabetes. AB - AIMS: The association between BMI and low levels of B-type natriuretic peptide (BNP), a marker of heart failure, has been demonstrated in a large population based cohort. We examined the effects of obesity on BNP levels in patients with diabetes that are often associated with obesity and a higher risk for heart failure. METHODS: Plasma BNP levels, BMI, and cardiac function parameters were measured in 608 patients with type 2 diabetes. A computed tomography scan was performed to measure abdominal fat. RESULTS: In multivariable regression analyses adjusted for age, sex, systolic blood pressure, pulse rate, serum creatinine, asynergy, left atrial dimension, percent fractional shortening, and left ventricular mass, there was an inverse relationship between BMI and BNP (p<0.001). Obese individuals with 252 years ago) who were receiving long-term hemodialysis therapy using tunneled hemodialysis catheters. Both were admitted to the hospital with catheter-related bacteremia. Blood cultures showed methicillin resistant Staphylococcus aureus (MRSA) in both cases. Transesophageal echocardiography was negative for the presence of valvular endocarditis, but showed lead-associated vegetation in both cases. Intravenous antibiotic therapy was initiated, and both the tunneled hemodialysis catheters and cardiac devices were removed by a cardiothoracic surgeon. The catheter tip and leads cultures showed MRSA in both cases. After resolution of bacteremia, both patients received an epicardial cardiac device. Antibiotic therapy was continued for 6 weeks. Renal physicians providing dialysis therapy should be aware that catheter-related bacteremia could cause contamination of transvenous pacemaker leads. Because catheter-related bacteremia is a frequent complication, epicardial leads might be considered as an alternative route to provide cardiac support to catheter consigned patients. Epicardial leads do not navigate through the central veins, lie in the path of blood flow, or cause central venous stenosis. PMID- 20363543 TI - "If your shoes are raggedy you get talked about": symbolic and material dimensions of adolescent social status and health. AB - This paper examines the interaction of symbolic and material dimensions of social status for African American adolescents and its relationship with blood pressure. Mixed ethnographic methods were used to develop cultural models of social status for urban African American teens in a predominantly African American lower-income community west of Chicago. Resting blood pressure and covariate data were collected, as well as standardized measures of perceived stress and social standing. Findings show that, adjusting for covariates, adolescents' consumption of symbolic status goods is significantly associated with their blood pressure, dependent upon parental economic resources. The political economy of status consumption, the underlying contexts of racial and economic inequality, and the implications of these findings for health disparities are discussed. PMID- 20363544 TI - Low-grade mucoepidermoid carcinoma of the intraoral minor salivary glands with cervical metastasis: report of 2 cases and review of the literature. PMID- 20363545 TI - Retrospective chart analysis on survival rate of fixtures installed at the tuberosity bone for cases with missing unilateral upper molars: a study of 7 cases. AB - PURPOSE: To evaluate the survival rate of implants placed in the maxillary tuberosity region using the fixed prosthesis in partially edentulous cases. MATERIALS AND METHODS: Of implant-treated patients who visited Kyung Pook National University Hospital, 7 partially edentulous patients (2 male and 5 female; mean age, 52.3 years; range, approximately 43 to 65) were selected according to the following criteria: 1) less than 3-mm thickness alveolar bone reaming at the first molar area and 2) 1 to 2 fixture premolars, with the additional implant at the maxillary tuberosity region. For the control group, patients who had nontuberosity areas were selected. After 1 to 7 years, marginal bone level, fixture mobility, and radiolucency of tuberosity fixtures of the fixed prostheses were evaluated by digital panorama (Starpacs, Infinitt, Seoul, Korea). RESULTS: None of the fixtures of the tuberosity-installed implants for 1 to 7 years failed. The marginal bone level around the implants of the maxillary tuberosity 1 to 6 years (average 3.4 years) after the final prostheses was approximately 0.6 to 1.3 mm, with an average of 0.94 mm. CONCLUSION: The fixture installation at the maxillary tuberosity using the unilateral partially edentulous implant-fixed prosthesis would be a clinically acceptable treatment module. PMID- 20363546 TI - Intraoral approach technique for treating trismus caused by fibrodysplasia ossificans progressiva. PMID- 20363547 TI - Nerve growth factor and tyrosine kinase A receptor in oral squamous cell carcinoma: is there an association with perineural invasion? AB - PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. MATERIALS AND METHODS: We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. RESULTS: Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group. CONCLUSION: This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome. PMID- 20363548 TI - Outcomes of open versus closed treatment of mandibular subcondylar fractures: a prospective randomized study. AB - PURPOSE: To compare open reduction and internal fixation with closed treatment and maxillomandibular fixation for the management of subcondylar fractures of the mandible. PATIENTS AND METHODS: Forty patients with subcondylar fractures of the mandible were evaluated. All fractures were displaced; either angulated between 10 degrees and 35 degrees or the ascending ramus was shortened by more than 2 mm. Clinical and radiographic evaluation was performed 6 months after the trauma. Clinical parameters included mouth opening, protrusion, laterotrusion, deviation on mouth opening, and occlusion. Radiographic parameters included level of the fracture, deviation of the fragment, and shortening of the ascending ramus. Subjective parameters included pain according to a visual analog scale. Nonparametric data were compared for statistical significance with a chi(2) analysis and parametric data with an independent samples t test (P < .05). RESULTS: Correct anatomical position of the fragments was achieved significantly more accurately in the operative group in contrast to the closed treatment group. Regarding mouth opening/lateral excursion/protrusion, significant (P = .00) differences were observed between both groups (open 39.6/12.5/5.9 mm vs closed 33.5/9.8/4.1 mm). The visual analog scoring revealed significant (P = .00) difference with less pain in the operative treatment group (1.1 open vs 5.2 closed). No statistically significant difference was found between the 2 groups for occlusion (P = .86). CONCLUSION: Both treatment options for condylar fractures of the mandible yielded acceptable results. However, operative treatment was superior in all objective and subjective functional parameters except occlusion. PMID- 20363549 TI - Editorial comment on: complications of laparoscopic and percutaneous renal cryoablation in a single tertiary referral center. PMID- 20363550 TI - Complications of laparoscopic and percutaneous renal cryoablation in a single tertiary referral center. AB - BACKGROUND: Laparoscopic cryoablation (LCA) and percutaneous cryoablation (PCA) of small renal masses have gained popularity, but only limited data exist on the complication rates. OBJECTIVES: In this study, we report on postoperative complications associated with LCA and PCA in a single tertiary center experience. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective review of electronic medical records for patients undergoing LCA or PCA between 2001 and 2008 at our institution. INTERVENTIONS: All patients underwent LCA or PCA. MEASUREMENTS: Demographics, radiographic variables, and complication rates were compared between the two groups. Complications were classified according to the modified Clavien system. RESULTS AND LIMITATIONS: Of a total of 195 patients included in this study, 72 underwent LCA and 123 underwent PCA. There were no differences in demographics between the groups. We observed complications in 10 LCA procedures (13.9%) and 26 PCA procedures (21.1%) (p=0.253). The distribution of the complications differed significantly between the groups with mild complications (grades 1 and 2) more common in the PCA group (20.3% vs 5.6%, respectively; p=0.001), whereas severe events (grades 3 and 4) were more frequent in the LCA group (8.3% vs 0.8%, respectively; p=0.011). On multivariate analysis, age and body mass index were inversely associated with complications, whereas female gender, multiple tumors, and preexisting comorbidities showed a trend toward increased risk. CONCLUSIONS: LCA and PCA, although minimally invasive, are not void of complications. Most of the complications encountered are mild; however, severe (grade 3 or 4) events may occur in up to 3.6% of patients. PCA may be associated with a higher rate of complications, although most of these are mild and transient. However, on multivariate analysis, the chosen ablative approach (laparoscopic or percutaneous) is not associated with the risk of complications. PMID- 20363551 TI - Treating refractory painful bladder syndrome/interstitial cystitis: is there a true organ target? PMID- 20363552 TI - Defining and treating high-risk prostate cancer: can we do better? PMID- 20363553 TI - Significance of the T2*-weighted gradient echo brain imaging in patients with infective endocarditis. AB - BACKGROUND: Although aneurysm formation accompanying parenchymal hemorrhage is one of devastating complications in the central nerves system (CNS), imaging studies of the brain are not routinely warranted in patients with infective endocarditis (IE). To assess the clinical importance for detecting silent lesions in the central nervous system, we investigated hypointense signal spots detected on the brain T2*-weighted MR imaging in patients with IE. METHODS AND RESULTS: Eleven patients with IE were retrospectively reviewed. Seven patients (63.6%) showed hypointense signal spots on T2*-weighted MR images. The number of hypointense signal spots increased within only a few weeks in five patients. CONCLUSION: The brain T2*-weighted MR imaging in patients with IE may have a potential role to detect CNS lesions with clinical significance of potentially high risk of intracranial hemorrhage. T2*-weighted hypointense signal spots may be specific to brain involvement, and be quite useful in monitoring CNS lesions associated with IE, even if they are asymptomatic. PMID- 20363554 TI - Acute vasospasm following transcallosal resection of a xanthogranulomatous colloid cyst of the 3rd ventricle. AB - We present the first case of a 57 year old man who developed severe, acute vasospasm following transcallosal resection of an unusual, xanthogranulomatous colloid cyst. The 16 year history of growth of this cyst may have resulted in its unusual pathology, and the subsequent vasospastic reaction to its excision. We discuss the potential pathological relationship between the inflammatory nature of the cyst, chemical meningitis and vasospasm, and what this implies about vasospasm in general. The severe, life-threatening vasospasm affected all four major vessels and required aggressive management by endovascular injection of nimodipine and angioplasty, with good recovery. The case illustrates a previously undescribed sequel of surgery for this condition, demonstrates an effective treatment and offers possible insights into the pathogenesis of vasospasm. PMID- 20363555 TI - Advanced oxidation of amoxicillin by Fenton's reagent treatment. AB - Advanced oxidation of amoxicillin was realized in aqueous solution by using Fenton's reagent treatment. Box-Behnken statistical experiment design was used to determine the effects of reagent concentrations on amoxicillin degradation and mineralization. Amoxicillin (10-200 mg L(-1)), hydrogen peroxide (10-500 mg L( 1)) and Fe(II) (0-50 mg L(-1)) concentrations were considered as independent variables in batch oxidation experiments. Percent amoxicillin and total organic carbon (TOC) removals (mineralization) were considered as the objective functions to be maximized. Required reaction times were 2.5 min and 15 min, respectively for degradation and mineralization of amoxicillin. Both peroxide and amoxicillin concentrations affected the extent of amoxicillin degradation and mineralization. Complete amoxicillin degradation was obtained within 2.5 min while 37% mineralization took place within 15 min. The optimum peroxide/Fe/amoxicillin ratio resulting in complete amoxicillin degradation and 37% mineralization was 255/25/105 mg L(-1). PMID- 20363556 TI - Mapping human vulnerability to chemical accidents in the vicinity of chemical industry parks. AB - China is suffering from severe pollution accidents which may have catastrophic impacts on the local population and environment. Some questions are unclear to local governments and industry operators like "who are vulnerable to the chemical risks?" and "what is the magnitude of vulnerability?". This paper concentrates on exploring the concepts of human vulnerability and the methodology of analyzing human vulnerability to chemical accidents in the vicinity of chemical industry parks. A conceptual model of human vulnerability to chemical accidents is developed, revealing the roots of human vulnerability and emphasizing its role in risk management. A geographical information system (GIS)-based methodology for mapping vulnerability is proposed and applied to the Nanjing Chemical Industry Park in China. By combining physical vulnerability and social vulnerability spatially, the total vulnerability is revealed to better respond to accidents. It is proposed to improve traffic lines and allocation of medical services, and include vulnerability assessment in land-use planning to reduce future risks. In other words, it seems feasible and effective to reveal physical, social and total vulnerability of residents in the vicinity of chemical risk sources. PMID- 20363557 TI - A novel full recycling process through two-stage anaerobic treatment of distillery wastewater for bioethanol production from cassava. AB - In the present study, a novel full recycling process for bioethanol production was investigated, where three mathematical models were established to simulate the accumulation of major soluble inhibitory substances, including organic compounds, total ions, volatile fatty acids (VFAs) and colorants. These inhibitory substances in the reused water reached a relative steady state after 3 7 batches of anaerobic treatment and recycling process, which coincided with the results of mathematical models. There were no negative effects of these inhibitory substances on ethanol fermentation and the final ethanol yield, fermentation time, starch utilization ratio were very close to that of the conventional process using tap water. However, approximately 7.54% (w/w) of water was lost during each circulation, which was replenished in subsequent circulations, to assure consistent fermentation broth volume. This novel process was confirmed to have a stable operation over 13 recycles. It is concluded the stable states of the inhibitory substances in the reused water can assure this recycling process will run successfully. PMID- 20363558 TI - Hydrothermal removal of Sr2+ in aqueous solution via formation of Sr-substituted hydroxyapatite. AB - We removed Sr(2+) in simulating wastewater and simultaneously prepared Sr substituted hydroxyapatite via chemical precipitation and hydrothermal treatment. Both higher initial pH value and higher molar ratio of Sr/(Sr+Ca) contributed to lower residual Sr(2+) concentration and higher removal efficiency. About two thirds of Sr(2+) residual in solution after chemical precipitation were further reduced by hydrothermal treatment. The optimal Sr removal result was 99.66% with an ultimate concentration of 2.0 mg L(-1) when the initial pH was 12 and Sr/(Sr+Ca) was 0.2. Sr-substituted hydroxyapatite phase with hexagonal structure was identified by XRD and EDS results. However, it was found that SrHPO(4) phase was formed in the samples with high Sr composition. The lattice constants became larger with the increase of Sr(2+) and the crystallinity became higher with the increase of pH value. Rod-like particles were observed in SEM images of synthesized Sr-substituted hydroxyapatite samples, with the size of 20-30 nm in width and 70-100 nm in length. With little secondary waste and simple treating procedure, this method is an effective and prospective measure to deal with (90)Sr in nuclear waste and industry wastewater. PMID- 20363559 TI - Effect of particle size in a limestone-hydrochloric acid reaction system. AB - Experimental characterization of the wet flue gas desulfurization process is carried out using a model limestone-hydrochloric acid reaction system, with in situ measurement of the dissolution rate and particle size distribution. The limestone source, initial particle size distribution, working temperature and pH value are varied in large ranges. The dissolution rate is found to be higher when the average particle size is smaller, the temperature is higher, or the pH is lower. An empirical equation is established to correlate the dissolution rate with the particle size and working conditions, which agrees well with measurements. The results may be useful for providing insights to improve the efficiency of the wet flue gas desulfurization process, as well as other solid particle-liquid solution reactions. PMID- 20363560 TI - Recovery of platinum from spent catalysts by liquid-liquid extraction in chloride medium. AB - This work examines a hydrometallurgical route for processing spent commercial catalysts (Pt and PtSnIn/A(2)O(3)) used in Brazilian refineries for recovery of the noble metal with less final wastes generation. Samples were initially pre oxidized (500 degrees C, 5 h) in order to eliminate coke. The basis of the present route is the partial dissolution of the pre-oxidized catalyst in aqua regia. Temperature and time necessary to dissolve all platinum were optimized in order to reduce the operation severity and aluminum solubilization. All platinum and 16-18 wt.% of aluminum were dissolved at 75 degrees C in 20-25 min. Separation of platinum from the acidic solution was accomplished by solvent extraction. The best extractant (> 99 wt.%) was Aliquat 336 (a quaternary ammonium salt) in one stage (A/O phase ratio = 1, v/v). Platinum was stripped (> 99.9 wt.%) in one stage (A/O phase ratio = 1, v/v) with aqueous sodium thiosulfate (> or = 0.75 mol L(-1)). Black platinum was obtained from this solution via reduction with magnesium or ascorbic acid. PMID- 20363561 TI - A screened hybrid density functional study on energetic complexes: cobalt, nickel and copper carbohydrazide perchlorates. AB - The molecular geometry, electronic structure, infrared spectra and thermochemical properties of cobalt and nickel tris(carbohydrazide) perchlorates (CoCP and NiCP) as well as copper bis(carbohydrazide) perchlorate (CuCP) were investigated using the Heyd-Scuseria-Ernzerhof (HSE) screened hybrid density functional. The results show that both perchlorate ions coordinate with the copper atom, and the interactions between copper and perchlorate are ionic, whereas all the metal carbohydrazide interactions are covalent. Due to the delocalization from the sigma(N-H) bond orbital to the n*(M) antibond orbital, the amino stretching vibrations of these complexes show considerable red-shift compared with those of free carbohydrazide ligand. The calculated heats of reaction and formation indicate that the formations of these complexes are exothermic, and the order of their thermal stability is NiCP>CoCP>CuCP. These agree well with the experimental results. Finally, we find that there is a relationship between the energy gap and impact sensitivity. PMID- 20363562 TI - Detection of Babesia EU1 in Ixodes ricinus ticks in northern Italy. AB - Babesia EU1, a potentially important emerging zoonotic pathogen, already detected in ticks and wild ruminants of different European Countries, was found in three pools of Ixodes ricinus nymphs in three different sites located in a single District of north-eastern Italy. Totally 356 ticks (60 pools) were collected from the environment during a surveillance activity in the year 2006. Babesia EU1 estimated individual tick prevalence in the area is 0.85%. The finding that also in northern Italy the tick population is carrying Babesia EU1 suggests a wide geographical spreading of this zoonotic pathogen in Europe. PMID- 20363563 TI - Biological characterization and pathogenicity of three Haemonchus contortus isolates in primary infections in lambs. AB - The biological characterization and differential pathogenicity of three isolates of Haemonchus contortus, one autochthonous (Aran 99) and two allochthonous (Moredun Research Institute, MRI, and Merck Sharp and Dohme, MSD) were studied by primary experimental infection of Manchego lambs. Thus, six female lambs (5.5 months old) were infected with 12,000 L3 larvae of each helminth isolate. Parasitological (pre-patent period, parasite egg shedding dynamics), biopathological (packed cell volume (PCV), haemoglobin concentration, plasma proteins, serum pepsinogen) and zootechnical parameters (live weight gain, thoracic perimeter) were measured throughout the study. After sacrifice (85 days post-infection (pi)), lamb carcasses were inspected for parasite burden and development (establishment rate, male/female ratio, degree of parasite development), and the average carcass weight of the experimental groups was compared. The autochthonous combination (Manchego lambs-Aran 99) had a longer pre patent period (28 days) and a significantly different pattern of egg elimination (maximum elimination on day 80 pi). The establishment rate and parasite burden (average values of 8.18% and 988 adult helminths, respectively) were both low, with no significant differences between isolates. There were no significant differences in parasitic nematode development in terms of size and weight (1264.66 microm and 149.45 microg for male worms and 2093.33 microm and 411.46 microg for females, respectively), although Aran 99 females weighed less (p<0.05). All isolates induced a slight but significant reduction of PCV values from day 23 pi onwards. Inter-isolate differences were found, with the effects in the case of MSD being more pronounced. Variations of serum protein levels were minimal in all lamb groups. The live weight gain of MSD- and Aran 99-infected animals was significantly lower (p<0.05) than for MRI-infected lambs and uninfected control animals. Carcass yield from the lambs infected with the autochthonous isolate (Aran 99) was lower. The MSD isolate therefore showed a higher comparative pathogenicity. PMID- 20363564 TI - Molecular predictive and prognostic markers in colon cancer. AB - Colorectal cancer remains one of the major cancer related death despite progress in the cytotoxic treatment of colorectal cancer (CRC) over the past decade. The introduction of targeted agents has improved the progression free and overall survival of metastatic disease. However, 40-50% of patients do not experience beneficial effects and it remains a challenge to select patients likely to respond to therapy. Several new molecular predictive and prognostic markers have been identified and are now being translated into routine clinical practice. K Ras mutation is the first established molecular marker with a lack of response in K-Ras mutated patients treated with an epidermal growth factor receptor (EGFR) targeted therapy. The validation of predictive and prognostic markers will result in more successful and less toxic therapeutic regimens for cancer patients. This review aims to summarize the most important currently available predictive and prognostic molecular markers in colorectal cancer. PMID- 20363565 TI - Is thermogenesis a significant causal factor in preventing the "globesity" epidemic? AB - During the last four decades the world has experienced an epidemic of overweight individuals in affluent as well as developing countries. The WHO has predicted a "globesity epidemic" with more than 1 billion adults being overweight and at least 300 million of these being clinically obese. Obesity among children and adolescents is of great significance. From a global population perspective, this epidemic in weight gain and its sequelae are the largest public health problems identified to date and have very significant adverse implications for population health, and have by now almost reached the proportion of a pandemic. While genetic changes have been discussed as a cause of the epidemic, there has been too little time since its start to enable enough genetic adaptation to take place for this to provide a valid explanation. Traditionally positive energy balance and sedentary life style have been regarded as the primary causal factors; however, these factors have so far failed to provide explanations for the entire problem. For these reasons it seems warranted to investigate other possible co factors contributing to the "globesity epidemic" and to find efficient strategies to counteract further increases in the size and nature of the epidemic. The purpose of this paper is to discuss a potential preventive co-factor, thermogenesis. Special attention has been paid to the influence of ambient temperature as a grossly neglected factor in the debate. As most people today live and work at ambient temperatures close to their body temperature (the thermal neutral point), we hypothesise that this is an important causal co-factor in the "globesity" epidemic. The hypothesis: The null hypothesis that adaptive thermogenesis in brown adipose tissue in adult humans is not significant for weight loss is rejected. We propose the hypothesis that homoeothermic living conditions close to the thermogenic neutral level is an important causal co factor in the "Globesity" Epidemic. PMID- 20363566 TI - Osteonecrosis of the scaphoid after scapholunate interosseous ligament repair and dorsal capsulodesis: case report. AB - Scapholunate interosseous ligament repair with dorsal capsular augmentation is an established surgical treatment for traumatic scapholunate instability. We report a case of scaphoid osteonecrosis that developed after this procedure and discuss the possible causes of this complication. PMID- 20363567 TI - [Management of spontaneous miscarriage in the first trimester]. PMID- 20363568 TI - [Feasibility and short-term morbidity of laparoscopic sacrocolpopexy with previous genital prolapse surgery]. AB - OBJECTIVES: To value feasibility and short-term morbidity of laparoscopic sacrocolpopexy for recurrent genital prolapse. PATIENTS AND METHODS: From a retrospective study, 43 women were operated on for recurrent genital prolapse (PR), 155 women were operated on for genital prolapse without previous prolapse surgery (PNR). The feasibility and the rate of per and postoperative complication were determined in both groups. RESULTS: Thirty-eight women (88.4 %) of the PR group had an entire procedure associating an anterior and a posterior mesh against 153 (98.7 %) in the PNR group (p=0.001). The rate of visceral injury was higher in the PR group than in the PNR group (9.3 % versus 3.2 %, p=0.09). The rate of rectal injury was 2 %. After an average follow-up of 7 months (minimum: 1 month; maximum: 45 months), the rate of mesh exposure was higher in the PR group than in PNR group (4.7 % versus 1.3 %, p=0.17). The rate of imperfect result after surgery was 4.7 % in the PR group and 9.2 % in the PNR group (p=0.34). Six women were reoperated for a recurrent genital prolapse. CONCLUSION: The laparoscopic sacrocolpopexy is a feasible procedure to treat recurrent genital prolapse. This needs a surgical team able to manage peroperative incident. PMID- 20363569 TI - Isolation of Mycobacterium avium subspecies paratuberculosis from muscle and peripheral lymph nodes using acid-pepsin digest prior to BACTEC culture. AB - Meat has received little attention regarding human exposure to Mycobacterium avium subsp. paratuberculosis, a possible infectious trigger of Crohn's disease. Meat has less contamination with other organisms than gut tissues, facilitating modifications to existing decontamination protocols prior to BACTEC culture that could increase analytical sensitivity. Using spiked meat samples we trialled enzymatic and chemical digestion techniques to concentrate larger starting samples, and modifications to existing clinical mycobacteriological decontamination protocols. An acid-pepsin digestion method using a 20 g sample was considerably more sensitive (detection limit 0.88 log(10) viable organisms per gram) than previous techniques. However, it was cumbersome for routine use, and subject to frequent contamination. Modifications to an existing centrifugation protocol yielded a simple, robust technique with slightly improved sensitivity (detection limit 1.77 log(10) per gram). Use of these sensitive tests in parallel identified M. a. paratuberculosis in the muscle of 59% and peripheral lymph nodes (PLN) of 85% of clinically infected sheep. The numbers of M. a. paratuberculosis in these infected tissues were low (1.67+/-0.92 log(10) per gram in muscle and 2.06+/-0.69 log(10) per gram in PLN), such that many would not have been detected by routine methods. Fewer subclinically infected animals with gross lesions harboured M. a. paratuberculosis in meat (4.5%) or PLN (32%), and the numbers of organisms in such infected animals were lower. Because most animals raised specifically for meat production are young and unlikely to be heavily infected, and because meat is usually consumed cooked, the risk of human exposure to viable M. a. paratuberculosis via meat may be small. Measures to prevent heavily infected animals, especially those with clinical signs, from entering the human food chain would further reduce this risk. PMID- 20363570 TI - Automated toxicological screening reports of modified Agilent MSD Chemstation combined with Microsoft Visual Basic application programs. AB - Agilent GC-MS MSD Chemstation offers automated library search report for toxicological screening using total ion chromatogram (TIC) and mass spectroscopy in normal mode. Numerous peaks appear in the chromatogram of biological specimen such as blood or urine and often large migrating peaks obscure small target peaks, in addition, any target peaks of low abundance regularly give wrong library search result or low matching score. As a result, retention time and mass spectrum of all the peaks in the chromatogram have to be checked to see if they are relevant. These repeated actions are very tedious and time-consuming to toxicologists. MSD Chemstation software operates using a number of macro files which give commands and instructions on how to work on and extract data from the chromatogram and spectroscopy. These macro files are developed by the own compiler of the software. All the original macro files can be modified and new macro files can be added to the original software by users. To get more accurate results with more convenient method and to save time for data analysis, we developed new macro files for reports generation and inserted new menus in the Enhanced Data Analysis program. Toxicological screening reports generated by these new macro files are in text mode or graphic mode and these reports can be generated with three different automated subtraction options. Text reports have Brief mode and Full mode and graphic reports have the option with or without mass spectrum mode. Matched mass spectrum and matching score for detected compounds are printed in reports by modified library searching modules. We have also developed an independent application program named DrugMan. This program manages drug groups, lists and parameters that are in use in MSD Chemstation. The incorporation of DrugMan with modified macro modules provides a powerful tool for toxicological screening and save a lot of valuable time on toxicological work. PMID- 20363571 TI - GC-IRD methods for the identification of some tertiary amines related to MDMA. AB - Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the drug of abuse; 3,4-MDMA and its regioisomer; 2,3-MDMA, from a set of seven tertiary amines which have an isobaric or regioisomeric relationship with the MDMAs. These compounds include three ring substituted regioisomers of 2-dimethylamino-1-(methoxyphenyl)ethanone, two ring regioisomers of N,N-dimethyl-2-(methoxymethylphenyl)ethanamine in addition to N,N dimethyl-2-(2,3- and 3,4-methylenedioxyphenyl)ethanamine. The major mass spectral fragments for each of these unique isomers occur at equivalent mass and all have equal molecular weight. Thus, gas chromatography with mass spectrometry detection (GC-MS) does not provide sufficient information for the confirmation of identity of any one of these isomers to the exclusion of the other compounds. The infrared spectra for these compounds allow for identification of any one of these amines. This differentiation is accomplished without the aid of chemical derivatization. The IR spectra served to divide the studied compounds into four groups depending on their absorption bands in the region 2700-3100 cm(-1). Moreover, compounds with different ring substitution pattern within each group can be differentiated by several bands in the 700-1700 cm(-1) region. These regioisomeric substances are well resolved by GC on Rtx-1 stationary phase and the vapor-phase infrared spectra clearly differentiate among this set of compounds. PMID- 20363572 TI - [Vascular prophylaxis after stroke or a transient ischemic event]. PMID- 20363573 TI - Radiation dose and cancer risk from pediatric CT examinations on 64-slice CT: a phantom study. AB - OBJECTIVE: To measure the radiation dose from CT scans in an anthropomorphic phantom using a 64-slice MDCT, and to estimate the associated cancer risk. MATERIALS AND METHODS: Organ doses were measured with a 5-year-old phantom and thermoluminescent dosimeters. Four protocols; head CT, thorax CT, abdomen CT and pelvis CT were studied. Cancer risks, in the form of lifetime attributable risk (LAR) of cancer incidence, were estimated by linear extrapolation using the organ radiation doses and the LAR data. RESULTS: The effective doses for head, thorax, abdomen and pelvis CT, were 0.7mSv, 3.5mSv, 3.0mSv, 1.3mSv respectively. The organs with the highest dose were; for head CT, salivary gland (22.33mGy); for thorax CT, breast (7.89mGy); for abdomen CT, colon (6.62mGy); for pelvis CT, bladder (4.28mGy). The corresponding LARs for boys and girls were 0.015-0.053% and 0.034-0.155% respectively. The organs with highest LARs were; for head CT, thyroid gland (0.003% for boys, 0.015% for girls); for thorax CT, lung for boys (0.014%) and breast for girls (0.069%); for abdomen CT, colon for boys (0.017%) and lung for girls (0.016%); for pelvis CT, bladder for both boys and girls (0.008%). CONCLUSION: The effective doses from these common pediatric CT examinations ranged from 0.7mSv to 3.5mSv and the associated lifetime cancer risks were found to be up to 0.16%, with some organs of higher radiosensitivity including breast, thyroid gland, colon and lungs. PMID- 20363574 TI - Technical aspects of MR perfusion. AB - The most common methods for measuring perfusion with MRI are arterial spin labelling (ASL), dynamic susceptibility contrast (DSC-MRI), and T(1)-weighted dynamic contrast enhancement (DCE-MRI). This review focuses on the latter approach, which is by far the most common in the body and produces measures of capillary permeability as well. The aim is to present a concise but complete overview of the technical issues involved in DCE-MRI data acquisition and analysis. For details the reader is referred to the references. The presentation of the topic is essentially generic and focuses on technical aspects that are common to all DCE-MRI measurements. For organ-specific problems and illustrations, we refer to the other papers in this issue. In Section 1 "Theory" the basic quantities are defined, and the physical mechanisms are presented that provide a relation between the hemodynamic parameters and the DCE-MRI signal. Section 2 "Data acquisition" discusses the issues involved in the design of an optimal measurement protocol. Section 3 "Data analysis" summarizes the steps that need to be taken to determine the hemodynamic parameters from the measured data. PMID- 20363575 TI - Fast detection of Candida albicans and/or bacteria in blood plasma by "sample self-focusing" using capillary electrophoresis-laser-induced fluorescence. AB - Detection of microbial contamination in blood plasma is critical and necessary in different medical and research fields. Most of the current standard procedures for the detection of bacteria and fungi can be time-consuming, for example, direct inoculation methods of microbial cultures in respective growth media can take a few days to several weeks. A fast analysis method with high sensitivity output such as CE-laser-induced fluorescence becomes an attractive alternative. Previously, a spacer-injection method with the use of zwitterionic surfactant (SB3-10) as a blocking agent to negate the cells' mobility, induce aggregation and single microbial peak formation in a buffer solution was reported. Here, a fast, simple direct method for microbial detection in blood plasma without using the spacer and blocking agent is reported. To compensate for the natural electrophoretic heterogeneity of microbes, a CTAB additive was used to sweep all microbial cells towards the plasma peak where a single sharp microbial peak is formed and detected. With the use of BacLight Green bacterial stain, the microbial peak, generally, can be detected within 10 min in front of the plasma peak using capillary electrophoresis coupled with laser-induced fluorescence detection. The LOD of microbes detectable were 5 cells per injection. This technique provides a great advantage over traditional, time-consuming microbial inoculation methods. PMID- 20363576 TI - Quantification of phenolic antioxidants in rat cerebrospinal fluid by GC-MS after oral administration of compounds. AB - A gas chromatographic-mass spectrometric (GC-MS) method for qualitative and subsequent quantitative analysis of phenolic antioxidants compounds, presents in olive oil, in rat cerebrospinal fluid (CSF) after oral administration of compounds is proposed. The procedure involves the extraction of compounds from the samples by a traditional microliquid-liquid extraction method, followed by a silylation step before the GC-MS analysis. The chromatographic separation was performed by using a low bleed DB5-MS fused-silica capillary column. The presence of 21 phenolic compounds was tested in CSF extracts and only free tyrosol, hydroxytyrosol and ferulic acid were detected. Those compounds were then quantitatively determined using the proposed methology. The molecular ion for silylated compounds appears at 370 m/z for hydroxytyrosol, 282 m/z for tyrosol and 338 m/z for ferulic acid respectively, while the base peak appears at 267 m/z, 179 m/z and 338 m/z. alpha-Naphthol was used as a surrogate (216 and 201 m/z). The detection capabilities obtained were 74, 92 and 79 ng/mL respectively. The method was applied to the determination of trace amounts of compounds in rat cerebrospinal fluid after oral administration. The animals were fed with a standard chow diet (free of phenolic antioxidants) in order to avoid the influence of any other component of the diet on the CSF of the animals. PMID- 20363577 TI - Simultaneous HPLC-F analysis of three recent antiepileptic drugs in human plasma. AB - An original high-performance liquid chromatographic method with fluorescence detection is presented for the simultaneous determination of the three antiepileptic drugs gabapentin, vigabatrin and topiramate in human plasma. After pre-column derivatisation with dansyl chloride, the analytes were separated on a Hydro-RP column with a mobile phase composed of phosphate buffer (55%) and acetonitrile (45%) and detected at lambda(em)=500 nm, exciting at 300 nm. An original pre-treatment procedure on biological samples, based on solid-phase extraction with MCX cartridges for gabapentin and vigabatrin, and with Plexa cartridges for topiramate, gave high extraction yields (>91%), satisfactory precision (RSD<6.4%) and good selectivity. Linearity was found in the 0.2-50.0 microg mL(-1) range for gabapentin, in the 1.0-100.0 microg mL(-1) range for vigabatrin and in the 1.0-50.0 microg mL(-1) range for topiramate, with limits of detection (LODs) between 0.1 and 0.3 microg mL(-1). After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. Accuracy results were satisfactory (recovery >91%). Therefore, the method seems to be suitable for the therapeutic drug monitoring (TDM) of patients treated with gabapentin, vigabatrin and topiramate. PMID- 20363578 TI - Care of the intubated emergency department patient. AB - BACKGROUND: Emergency physicians perform tracheal intubation and initiate mechanical ventilation for critically ill patients on a daily basis. With the current national challenges of intensive care unit bed availability, intubated patients now often remain in the emergency department (ED) for exceedingly long periods of time. As a result, care of the intubated patient falls to the emergency physician (EP). Given the potential for significant morbidity and mortality, it is crucial for the EP to possess the most current, up-to-date information pertaining to the care of intubated patients. DISCUSSION: This article discusses critical aspects in the ED management of intubated and mechanically ventilated patients. Specifically, emphasis is placed on providing adequate sedation and analgesia, limiting the use of neuromuscular blocking agents, correctly setting and adjusting the mechanical ventilator, utilizing appropriate monitoring modalities, and providing key supportive measures. Despite these measures, inevitably, some patients deteriorate while receiving mechanical ventilation. The article concludes with a discussion outlining a step-wise approach to evaluating the intubated patient who develops respiratory distress or circulatory compromise. With this information, the EP can more effectively care for ventilated patients while minimizing morbidity, and ultimately, improving outcome. CONCLUSION: Essential components of the care of intubated ED patients includes administering adequate sedative and analgesic medications, using lung protective ventilator settings with attention to minimizing ventilator-induced lung injury, elevating the head of the bed in the absence of contraindications, early placement of an orogastric tube, and providing prophylaxis for stress related mucosal injury and deep venous thrombosis when indicated. PMID- 20363579 TI - Worsening gait abnormalities in a 12-year-old child. PMID- 20363580 TI - Evaluation and management for carotid dissection in patients presenting after choking or strangulation. AB - BACKGROUND: Carotid dissection (CD) is often overlooked as a concern in strangulation and choking cases. When the diagnosis is considered, the question remains what is the best means of evaluation, and which imaging study should be obtained. OBJECTIVE: To evaluate the literature for evaluation of choking- and strangulation-related injuries and their association with CD. DISCUSSION: This article will review the literature on blunt carotid injuries, with particular attention to subjects with choking and strangulation mechanisms of injury, and will include important physical findings, when and which radiographic evaluations are indicated, and treatment. CONCLUSION: Although rare, CD can occur after strangulation and choking. When suspected, evaluation should include imaging studies including computed tomography angiography. PMID- 20363581 TI - Suspected brown recluse envenomation: a case report and review of different treatment modalities. AB - BACKGROUND: The Loxosceles reclusa, commonly known as the brown recluse spider, is responsible for virtually all cases of spider bites leading to a significant necrosis. CASE REPORT: We report the case of a 72-year-old man who presented to the Emergency Department complaining of back pain, weakness, and diarrhea. The patient stated that he sustained a bug bite 1 week before presenting to the hospital. His wound was necrotizing in nature and after an exhaustive work-up, the most likely etiology was found to be envenomation by a brown recluse spider, Loxosceles reclusa. CONCLUSION: This is an endemic cause of a necrotizing wound bite in areas of the Midwestern and Southern United States, but it is rarely reported in the Northeast. PMID- 20363582 TI - Tension hydrothorax in a pediatric patient with a ventriculopleural shunt. AB - BACKGROUND: Ventriculopleural shunts have been utilized in the management of hydrocephalus since the early 1900s. Shunt malfunctions can lead to fluid accumulation in the pleural space and a tension hydrothorax can develop. Improved diagnostic and therapeutic resources have led to an increasing number of ventriculopleural shunts being utilized in patients with symptomatic hydrocephalus. Emergency physicians are being called upon more frequently to diagnose and help manage many of the critical complications that can arise with ventricular shunts. OBJECTIVES: Very little literature exists concerning the evaluation and treatment of patients with a suspected tension hydrothorax secondary to a ventriculopleural shunt malfunction. If left unrecognized and untreated, tension pneumothoraces can progress and result in hemodynamic decompensation and cardiopulmonary arrest. Patient survival depends on early diagnosis and prompt fluid drainage in this clinically challenging scenario. CASE REPORT: This is the first article in the emergency medicine literature to describe the presentation and management of a pediatric patient who presents to the Emergency Department with a rare diagnosis of a tension hydrothorax secondary to a defective ventriculopleural shunt. CONCLUSION: The increasing number of ventriculopleural shunts being utilized requires emergency physicians to become familiar with the life-threatening complications that can be associated with these types of shunts. Correctly identifying this complication and initiating immediate treatment can lead to improved patient outcomes. PMID- 20363584 TI - Thrombotic mesenteric ischemia due to aortic dissection. PMID- 20363583 TI - Can we defer/omit a type and screen blood test for pregnant women who know their blood type? AB - BACKGROUND: Current clinical practice in many emergency departments (EDs) includes checking a type and screen blood test (T&S) for Rhesus (Rh) status on all pregnant patients presenting with vaginal bleeding or abdominal pain. The test is expensive, and awaiting results may delay disposition. OBJECTIVE: To determine if there is a subset of pregnant women who reliably know their blood type and for whom a T&S blood test to determine Rh status can be safely omitted or deferred. METHODS: A prospective study at two associated urban academic centers with an annual ED census of 150,000 patients was performed between January 2007 and June 2008. Pregnant patients who had a T&S obtained as part of their ED evaluation were enrolled. Subjects completed a standardized data form that requested demographic information and were asked to select "no," "maybe," or "yes, definitely" if they knew their blood type. Standard descriptive statistics with 95% confidence intervals were performed. RESULTS: There were 319 pregnant women enrolled in the study. Among the 106 subjects that reported "yes, definitely" they knew their blood type, 103 (97.2%; 95% confidence interval [CI] 94.0-100%]) identified their correct blood type and 105 (99.1%; 95% CI 97.2-100%) identified their correct Rh status. None of these subjects selected a positive Rh when they were in fact a negative Rh. All 14 (13.2%) subjects with a negative Rh status identified themselves as having a negative Rh. CONCLUSION: Pregnant women reporting that "yes, definitely" they know their blood type, are reliable. Deferring T&S testing test may be reasonable. PMID- 20363585 TI - Prognosis of extremity osteosarcoma in patients aged 40-60 years: a cohort/case controlled study at a single institute. AB - BACKGROUND: The outcome of older osteosarcoma patients with multi-disciplinary management has not been clearly defined. METHODS: We conducted a cohort (n=375) and a case-control (n=78) study on 26 older age patients (40-60 years) with localized osteosarcoma of extremity. In the case-control study, controls were matched for location and initial tumor volume. RESULTS: Compared to 349 younger patients, older age patients showed an osteolytic pattern on plain radiographs (P=0.05), fibroblastic subtype (P<0.01), and poor histologic response (P=0.03). Multivariate analysis revealed that a large absolute tumor volume (P<0.01), a tumor location in the proximal humerus (P=0.02), and a poor histologic response to preoperative chemotherapy (P<0.01) independently predicted poorer metastasis free survival. However, an older age showed marginal significance (P=0.09). A case-control study showed a higher proportion of the fibroblastic subtype and poor histologic response in the case group. Five-year metastasis-free survival rates for the 26 cases and 52 controls were 40.1+/-10.1% and 61.5+/-6.8%, respectively (P=0.02). CONCLUSIONS: Older age osteosarcoma patients showed an unfavorable histologic response to chemotherapy and lower survival than younger patients. Nevertheless, a further larger-scale study is required to confirm our observations. PMID- 20363586 TI - Systematic review and meta-analysis of the association between P53 codon 72 polymorphism and colorectal cancer. AB - BACKGROUND: A number of studies has evaluated the association between P53 codon 72 polymorphism and colorectal cancer. However, results were inconsistent. To clarify the role of this polymorphism in colorectal cancer, we conducted a meta analysis on this topic. METHODS: Two authors independently searched the PubMed and EMBASE database from 1966 to January 2010 for studies regarding the association of P53 codon 72 polymorphism with colorectal cancer. Summary odds ratios with their corresponding 95% confidence intervals were calculated by using random-effects model. RESULTS: The combined results showed that P53 codon 72 variant genotypes were not associated with colorectal cancer risk when compared to Arg/Arg genotype (Pro/Pro: OR = 1.02, 95% CI = 0.80-1.29; Arg/Pro: OR = 1.00, 95% CI = 0.86-1.16; Pro allele: OR = 1.00, 95% CI = 0.86-1.17). When stratifying for study population, design and cancer location, no statistically significant results were observed either. CONCLUSION: Our data indicate that the P53 codon 72 polymorphism may be not associated with colorectal cancer risk. PMID- 20363587 TI - Transradial and transbrachial arterial approach for simultaneous carotid angiographic examination and stenting using catheter looping and retrograde engagement technique. AB - BACKGROUND: The purpose of this study was to introduce a novel and safe technique with high procedural success for carotid artery stenting (CAS). METHODS: From April 2004 to May 2009, 161 patients underwent CAS using either a high transradial arterial approach (TRA, defined as 10 cm above styloid process) or a transbrachial arterial approach (TBA) with a 7F arterial sheath. Selective carotid angiography was performed using a 6F Kimny guiding catheter and Teflon wire (260 cm in length) by Catheter Looping And Retrograde Engagement Technique (CLARET) with the guiding catheter seated on the right coronary cusp and its tip engaged into the common carotid artery (CCA). Teflon wire was introduced into the CCA again after the diagnostic procedure, followed by replacement of the 6F Kimny guiding catheter by a 7F Kimny catheter for CAS using one of the following techniques: (1) direct-engagement method, i.e., from right innominate artery into the right CCA; (2) looping method plus double-wire technique (utilized two Teflon wires to provide an adequate support) for both the right and left CCA; and (3) looping method plus a PercuSurge balloon anchoring at the external carotid artery. RESULTS: This distinctive technique offered 100% diagnostic success and 99.4% CAS success. Two patients (1.2%) experienced major ischemic stroke after CAS and two (1.2%) died during hospitalization. CONCLUSION: The results of the present study showed that high TRA/TBA using CLARET for CAS in patients with severe carotid artery stenosis is safe and technically feasible with an extremely high success rate. PMID- 20363588 TI - Intestinal parasitic infections among intellectual disability children in rehabilitation centers of northern Iran. AB - Parasitic infection is highly prevalent throughout the developing countries of the world. These infections are the major problem in rehabilitation centers for the mentally retarded. There have been many reports about the prevalence of parasitic infection among different groups of people in Iran; however, the epidemiological data in intellectual disability (ID) individuals are rare and there are no such data from northern Iran. The aim of the present study was to determine the incidence of intestinal parasitic infections among the inhabitants of rehabilitation centers of Mazandaran province, northern Iran. A triple fecal specimens was collected from each of the 362 participants (183 males, 179 females) residing in six rehabilitation centers of Behshahr, Sari, Amol, Nowshahr and Ramsar. Each specimen was examined by direct wet mounting, formol-ether concentration, Ziehl-Neelsen and trichrome permanent staining. The overall infection rate of intestinal parasite was 26.2% (95 out of 362 subjects; 22.4% in males and 30.2% in females). Giardia lamblia was the most commonly found protozoan parasite (8.0%) followed by Entamoeba coli (5.5%), Blastocystis hominis (3.3%), Endolimax nana (2.8%) and Entamoeba histolytica (1.7%). Double infections were E. coli and B. hominis (1.1%), G. lamblia and Chilomastix mesnili (1.1%), G. lamblia and B. hominis (0.5%), G. lamblia and E. coli (0.5%), E. histolytica and E. coli (0.5%), E. nana and E. coli (0.5%) and E. nana and B. hominis (0.5%). No egg-positive case was found. These helminthic parasites were found to be not common among the participants, 75% of whom had been treated with mebendazole by guardians as a tradition, every 6 months. Nevertheless, our data in rehabilitation centers in northern Iran suggest that infection is not higher than that in community population in recent years in this geographical area. PMID- 20363589 TI - Possible regulatory factors for intra-abdominal fat mass in a rat model of Parkinson's disease. AB - OBJECTIVE: Patients with Parkinson's disease (PD) lose body weight primarily due to decreased body fat mass. The purpose of this study was to elucidate possible factors related to reduction in the intra-abdominal fat mass of 6-hydroxydopamine (6-OHDA)-treated rats, which are frequently used as an animal model for PD. METHODS: Sham-operated (NPD: n = 4) and unilaterally 6-OHDA-injected (PD: n = 4) 14-wk-old male Sprague-Dawley rats were fed a relatively high-fat diet for 2 wk, during which food intake and body weight were measured. After the 2-wk feeding period, intra-abdominal fat was dissected out and weighed. Carbohydrate and fat absorption-related gene expressions in the jejunum and serum insulin and glucose concentrations were analyzed. RESULTS: Although final body weights did not differ, total intra-abdominal fat weight, expressed relative to body weight, was significantly lower in the PD group than in the NPD group (P < 0.05). There were no significant differences between the two groups in the mRNA expression of carbohydrate and fat digestion/absorption-related genes in the jejunum, or in fat absorption efficacy assessed by fecal fat excretion. However, PD rats showed significantly lower serum insulin and higher glucose concentrations than NPD rats (P < 0.05). CONCLUSION: PD model rats displayed loss of intra-abdominal fat, similar to the progressive loss of fat in PD patients. Our results provide preliminary evidence that reduced lipogenesis due to lower insulin levels, rather than impaired digestion/absorption, might have been involved in this decrease in intra-abdominal fat mass. PMID- 20363590 TI - Venous thrombosis risk: effects of palm oil and hydrogenated fat diet in rats. AB - OBJECTIVE: We tested whether diets containing partially hydrogenated fat (PHVO, rich in trans fatty acids) or palm oil (PO, rich in saturated fat-C16 palmitic fatty acid) had different effects on the propensity for venous thrombosis, a marker of haemostatic cardiovascular risk. METHODS: Female Wistar rats were fed normolipidic diets containing PHVO or PO during lactation, and their young male pups were fed the same diets from weaning until the 180th day of life. We evaluated platelet fatty acid composition, serum lipids, platelet aggregation, clotting time, and venous thrombus formation. RESULTS: A significant and cumulative incorporation of trans fatty acid was observed only in the platelet lipids from the PHVO group, associated with an increased sensitivity to adenosine diphosphate (ADP) and venous thrombus formation in vivo. Platelets from rats raised on the PO diet also exhibited platelet aggregation induced by ADP and an increase in venous thrombus weight, with a concomitant increase in serum triglycerides. CONCLUSION: The prolonged replacement of dietary hydrogenated fat by PO impaired platelet aggregability and venous thrombosis, suggesting an increased risk of thromboembolic diseases. PMID- 20363591 TI - Aluminum contamination in products used in parenteral nutrition: has anything changed? AB - In July 2004, the U.S. Food and Drug Administration issued a mandate that required manufacturers to include the aluminum content on the labels of the additives commonly used in the compounding of parenteral nutrition solutions. It was the hope that practitioners would use this information to minimize the amount of aluminum exposure provided by parenteral nutrition to less than the 5 mCg/kg/d, the threshold deemed as "safe." Since that time, it has been difficult to easily incorporate these guidelines into clinical practice due to limitations in current product formulations. The purpose of this article is to revisit the rationale for the development of this mandate and to survey the literature since its implementation to determine if any new findings have emerged. A brief overview of aluminum toxicity, the patient populations at risk, treatment options, and compounding considerations is also presented. PMID- 20363592 TI - Outcome of a hospital based multidisciplinary weight loss program in obese Filipino children. AB - BACKGROUND: Childhood obesity is becoming a problem for Filipino children with an increasing national prevalence of pediatric overweight and obesity. A multidisciplinary approach combining behavioral therapy with diet and exercise is often advocated as having the greatest impact in pediatric weight management. OBJECTIVE: To determine the effects of a weight loss program, which is a staged 3 mo, multidisciplinary intervention consisting of combined dietary, exercise, and behavioral methods in obese children. RESEARCH METHODS AND PROCEDURES: Prospective study done in a hospital-based weight management center; duration of study: 15 mo (November 2005 to January 2008); participants: 44 obese children (aged 5-17 y; body mass index [BMI] 85th-99th percentile); outcome measures: change in weight, BMI, BMI z-score (SD score); secondary measures included changes in waist circumference, blood pressure, and body fat. Statistical tests: paired t tests, chi2 test, Wilcoxon ranked sum test, regression analysis, and ANOVA. RESULTS: At the end of the program, the patients demonstrated a decrease in weight, BMI, BMI z-score, body fat, systolic blood pressure, and waist circumference. Mean weight loss is 4.2 kg (P < 0.01) with an average of 5.3% weight loss; BMI decreased by 1.5 units (P < 0.01), BMI z-score by 0.15 (P < 0.004), body fat by 14% (P < 0.01), systolic blood pressure by 7.25 mm Hg (P < 0.05), and waist circumference by 5.4 cm (P < 0.05). Decrease in weight, BMI, and body fat were significantly correlated with number of sessions attended. CONCLUSION: The use of a multidisciplinary 3-mo staged program resulted in an effective weight loss in obese Filipino children, which was directly related to the frequency of sessions attended. PMID- 20363593 TI - Micronutrient deficiencies after bariatric surgery. AB - It has been estimated that approximately 220,000 people with morbid obesity underwent bariatric surgery in 2008. Modification of the gastrointestinal tract affects absorption and health care professionals counseling bariatric patients need to be aware of possible micronutrient deficiencies and their symptoms. A systematic review of several databases and bariatric surgery center websites on the Internet was conducted from January 1980 to July 2009 to identify literature related to micronutrient deficiencies occurring after bariatric surgery. Keywords used individually or in combination were bariatric surgery, obesity, vitamin/mineral deficiencies, altered gastrointestinal function, nutrient absorption, nutrient supplementation, and metabolic complications, and were variously combined in the search list. Based on this review, all patients scheduled for bariatric surgery should receive daily multivitamin and multitrace mineral supplements. The literature suggests that bariatric surgery patients are at risk for deficiency of the following nutrients after surgery: vitamins B(12), B(1), C, folate, A, D, and K, along with the trace minerals iron, selenium, zinc, and copper. Over-the-counter multivitamin and mineral supplements do not provide adequate amounts of certain nutrients such as vitamin B(12), iron, or fat-soluble vitamins and patients will require additional doses of prophylactic supplementation life-long to maintain optimal micronutrient status. In addition, preconception care for adequate prenatal supplementation is critical for pregnant women who have undergone bariatric surgery, as iron, vitamin A, vitamin B(12), vitamin K, and folate deficiencies are associated with maternal and fetal complications, including severe anemia, congenital abnormalities, low birth weight, and failure to thrive. All bariatric surgery patients would be best served by receiving regular monitoring of serum nutrient levels starting at 3 mo after surgery and periodically thereafter. PMID- 20363594 TI - Effects of vitamin A deficiency on mucosal immunity and response to intestinal infection in rats. AB - OBJECTIVE: Vitamin A deficiency is associated with an increased incidence of infectious respiratory and alimentary tract diseases in children, and vitamin A supplementation can prevent and assist in treating these diseases. To clarify the mechanisms of these associations, we investigated the effects of vitamin A deficiency on mucosal immunity to intestinal infection in rats. METHODS: Specific pathogen-free Sprague-Dawley rats received a vitamin A-free diet, with (n=20) or without (n=20) vitamin A supplementation. Intestinal infection was induced by oral inoculation of salmonella in 10 rats in each group. The rats were killed 3 d after infection was induced, and we measured the number, maturation, and activation of dendritic cells; the expression of Toll-like receptors 2 and 4; mRNA level of myeloid differentiation primary response gene (88) (MyD88, pattern recognition receptors and their adapter protein); immune cytokine production in the intestinal mucosa; and the amount of secretory immunoglobulin A in the gut. RESULTS: In vitamin-A deficient rats, the number of mucosal dendritic cells and the production of IL-12 markedly increased; the mucosal expressions of Toll-like receptor 2 and MyD88 were up-regulated, and secretions of interferon-gamma and secretory immunoglobulin A were decreased. Infection aggravated the damage to the intestinal mucosa and lowered immunity in vitamin-A deficient rats. CONCLUSION: Vitamin A deficiency damaged both humoral and cellular immunity in the mucosa. Modulation of dendritic cells is likely an important mechanism through which vitamin A deficiency affects mucosal immune responses against infection. PMID- 20363595 TI - Increased gut absorptive capacity in rats with severe head injury after feeding with probiotics. AB - OBJECTIVE: The absorptive capacity of the gut is decreased after severe head injury (SHI), and this may be related to poor recovery. Probiotics may be a promising approach to improving gut absorption. The aim of this study was to investigate the effect of probiotics on gut absorptive capacity (GAC) after SHI. METHODS: A rat model in which SHI was induced by air percussion was used. One hundred fourteen Sprague-Dawley rats were randomized into three groups: SHI followed by standard enteral nutrition (group A); SHI followed by standard enteral nutrition plus probiotics (group B); and standard chow diet ad libitum (group C, sham-operated). The enteral diets were infused for 14 d after SHI. RESULTS: SHI induced weight loss and decreased the serum concentration of D xylose and the apparent protein digestibility. Probiotics significantly improved GAC after SHI. Apparent protein digestibility and the concentration of D-xylose were lower in group A than in B or C after 14 d. The rats receiving probiotics showed less weight loss than group A. SHI induced intestinal flora dysfunction and a decrease in villus height and surface area. Digestive enzyme activities and gut motion were also depressed significantly, and these changes were closely related to the decrease in GAC. Probiotics increased villus height and surface area; Escherichia coli counts decreased significantly, and anaerobic counts increased. CONCLUSION: Probiotics improve the GAC after SHI, perhaps because of enhanced villus surface area, and correction of intestinal flora dysfunction. PMID- 20363596 TI - Utilization of magnesium during hypokinesia and magnesium supplementation in healthy subjects. AB - OBJECTIVE: The incompleteness of electrolyte utilization during hypokinesia and electrolyte supplementation is the defining factor of electrolyte metabolic changes, yet the effect of electrolyte supplementation and HK upon electrolyte utilization is poorly understood. To determine the influence of magnesium (Mg(2+)) supplementation and hypokinesia (diminished movement) on magnesium utilization, we investigated the use of Mg(2+) supplementation to establish its effect upon muscle Mg(2+) content and Mg2(2+) losses. METHODS: This study was conducted in 40 physically healthy male volunteers during a pre-experimental period of 30 d and an experimental period of 364 d. Subjects were equally divided into four groups: unsupplemented control subjects (UCSs), unsupplemented experimental subjects (UESs), supplemented control subjects (SCSs), and supplemented experimental subjects (SESs). A daily supplementation of 3.0 mmol of magnesium-chloride per kilogram of body weight was given to subjects in the SCS and SES groups. RESULTS: Muscle Mg(2+) content decreased (P < 0.05) and plasma Mg(2+) concentration and Mg(2+) loss in urine and feces increased (P < 0.05) in the SES and UES groups compared with their pre-experimental levels and values in their respective control groups (SCS and UCS). Muscle Mg(2+) content decreased more (P < 0.05) and plasma Mg(2+) concentration and Mg(2+) loss in urine and feces increased more (P < 0.05) in the SES group than in the UES group.The muscle Mg(2+) content and plasma Mg(2+) level and Mg(2+) losses did not change in the control groups. CONCLUSION: Daily Mg(2+) supplementation during prolonged hypokinesia decreases more muscle Mg(2+) content and Mg(2+)-deficient muscle increases more Mg(2+) loss in healthy subjects indicating lower Mg(2+) utilization with than without Mg(2+) supplementation. PMID- 20363597 TI - Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis. AB - OBJECTIVE: High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. METHODS: Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. RESULTS: The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). CONCLUSION: The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. PMID- 20363598 TI - Effect of gene dosage on single-cell hippocampal electrophysiology in a murine model of SSADH deficiency (gamma-hydroxybutyric aciduria). AB - Human and murine succinic semialdehyde dehydrogenase (SSADH; gamma-hydroxybutyric (GHB) aciduria) deficiency represents an epileptic disorder associated with hyperGABA- and hyperGHB-ergic states. Despite significant neurotransmitters alterations, well-defined single-cell electrophysiological studies, aimed to provide insight into regional neuropathology, have been lacking. In this study, we characterized the effect of residual SSADH enzyme function/increased GABA levels on single-cell hippocampal electrophysiology in SSADH+/+ (wild-type; WT), SSADH+/- (heterozygous; HET), and SSADH-/- (knock-out; KO) mice. Tonic extrasynaptic GABAA receptor (GABAAR)-mediated currents were elevated in HET and KO mice, whereas phasic synaptic GABAAR currents were unaltered in dentate gyrus granule cells. Similarly, tonic GABAAR-mediated currents were increased in dentate gyrus interneurons of KO animals, while phasic GABAergic neurotransmission was unaffected in the same cells. Our results indicate global disruption of cortical networks in SSADH KO mice, affecting both excitatory and inhibitory neurons. Our findings provide new clues concerning seizure evolution in the murine model (absence-->tonic-clonic-->status epilepticus), and extend pathophysiological insight into human SSADH deficiency. PMID- 20363599 TI - The nuclear matrix shell proteome of human epidermis. AB - BACKGROUND: Proteomic approaches have identified cancer specific biomarker proteins in the nuclear matrix fraction of cancer cells. We wanted to determine whether a similar approach could be used to investigate melanoma biomarkers. OBJECTIVE: Since it was not clear that a nuclear matrix fraction could be isolated from the intact human epidermis, we first wanted to determine whether a nuclear matrix fraction could be isolated from the intact epidermis of human skin. If this was possible, we secondarily wanted to compare the proteome of cultured melanoma and carcinoma cells to that of the intact epidermis. METHODS: We applied two-dimensional electrophoresis (2DGE) and LC/MS/MS to identify proteins isolated in the nuclear matrix shell protein fraction isolated from the human epidermis and from cultured primary skin and cancer cells. RESULTS: A subcellular fractionation of intact epidermis succeeded in yielding a nuclear matrix shell which made up approximately 40% of total tissue protein. Only 5-10% of total cell protein was fractionated in the nuclear matrix shell of cultured skin cells. The nuclear matrix shell of the intact epidermis was distinguishable from cultured keratinocytes or HaCaT cells by expression of keratin 1. The nuclear matrix of the epidermis was distinguishable from melanocytes and melanoma cells by expression of vimentin in melanocyte-derived cells and by expression of desmoplakin in the intact epidermis. CONCLUSION: The nuclear matrix-intermediate filament system can be isolated from the intact human epidermis. A careful examination of the protein composition of this subcellular fraction from the epidermis and skin cancers may identify useful cancer specific biomarkers. PMID- 20363600 TI - Controlling cellular activity by manipulating silicone surface roughness. AB - Silicone elastomers exhibit a broad range of beneficial properties that are exploited in biomaterials. In some cases, however, problems can arise at silicone elastomer interfaces. With breast implants, for example, the fibrous capsule that forms at the silicone interface can undergo contracture, which can lead to the need for revision surgery. The relationship between surface topography and wound healing--which could impact on the degree of contracture--has not been examined in detail. To address this, we prepared silicone elastomer samples with rms surface roughnesses varying from 88 to 650 nm and examined the growth of 3T3 fibroblasts on these surfaces. The PicoGreen assay demonstrated that fibroblast growth decreased with increases in surface roughness. Relatively smooth (approximately 88 nm) PDMS samples had ca. twice as much fibroblast DNA per unit area than the 'bumpy' (approximately 378 nm) and very rough (approximately 604 and approximately 650 nm) PDMS samples. While the PDMS sample with roughness of approximately 650 nm had significantly fewer fibroblasts at 24h than the TCP control, fibroblasts on the smooth silicone surprisingly reached confluence much more rapidly than on TCP, the gold standard for cell culture. Thus, increasing the surface roughness at the sub-micron scale could be a strategy worthy of consideration to help mitigate fibroblast growth and control fibrous capsule formation on silicone elastomer implants. PMID- 20363601 TI - In vitro permeation of diclofenac salts from lyotropic liquid crystalline systems. AB - In this paper we examined feasible correlations between the structure of different lyotropic mesophases and transdermal administration of three diclofenac derivatives with varying degrees of kosmotropic or chaotropic properties, solubilized within the mesophases. It was found that the most chaotropic derivative of diclofenac diethyl amine (DEA-DFC) interacted with the polar heads of glycerol monooleate (GMO), thus expanding the water-lipid interface of the lamellar and cubic mesophases. This effect was detected by an increase in the lattice parameter of both mesophases, enhanced elastic properties, and increased solid-like response of the systems in the presence of DEA. Potassium diclofenac (K-DFC), a less chaotropic salt, had less pronounced effect on the structural features of the mesophases. Kosmotropic Na+ salt (Na-DFC) had only minor influence on both lamellar and cubic structures. The locus of solubilization of the molecules with the host mesophases was correlated with their delivery. It was suggested that transdermal delivery of kosmotropic Na-DFC was accelerated by the aqueous phase and less constrained by the interaction with monoglyceride. On the other hand, the chaotropic cations (K+ and DEA+), presumably entrapped in the water-lipid interface, interacted with monoglyceride headgroups, which is likely to be the key cause for their sustained administration. PMID- 20363602 TI - Voltammetric sensor for buzepide methiodide determination based on TiO2 nanoparticle-modified carbon paste electrode. AB - In this work, we have prepared nano-material modified carbon paste electrode (CPE) for the sensing of an antidepressant, buzepide methiodide (BZP) by incorporating TiO2 nanoparticles in carbon paste matrix. Electrochemical studies indicated that the TiO2 nanoparticles efficiently increased the electron transfer kinetics between drug and the electrode. Compared with the nonmodified CPE, the TiO2-modified CPE greatly enhances the oxidation signal of BZP with negative shift in peak potential. Based on this, we have proposed a sensitive, rapid and convenient electrochemical method for the determination of BZP. Under the optimized conditions, the oxidation peak current of BZP is found to be proportional to its concentration in the range of 5 x 10(-8) to 5 x 10(-5)M with a detection limit of 8.2 x 10(-9)M. Finally, this sensing method was successfully applied for the determination of BZP in human blood serum and urine samples with good recoveries. PMID- 20363603 TI - Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property. AB - The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats. PMID- 20363605 TI - A Scandinavian audit of hospitalizations for chronic obstructive pulmonary disease. AB - In Scandinavia no large audits of hospitalizations for chronic obstructive pulmonary disease (COPD) have been performed, and data on adherence to national guidelines are scarce. The aims of the present study were to audit hospitalizations for COPD exacerbations in three Scandinavian hospitals with respect to incidence, patient population and standards of hospital care. Retrospectively all hospitalizations in the Departments of Internal and Respiratory Medicine in Ostersund Hospital (Sweden), Aalesund Hospital (Norway) and Trondheim University Hospital (Norway) from Jan 1 to Dec 31, 2005, with discharge ICD-10 diagnoses J43-J44, J96 + J44 or J13-18 + j44 were registered. A total of 1144 admissions (731 patients) were identified from patient administrative systems and medical charts. Among the admitted patients 27% were >80 years old, >50% had COPD stage III or IV, and 14% had respiratory acidosis at admittance. Patients with 3 or more admissions (13%) during 2005 accounted for 36% of all hospitalizations. One third of the patients were current smokers. Non invasive ventilation was used in 14% of the admissions, with large variation between centres. In-hospital mortality was 3.7%. In this first large Scandinavian audit of COPD-hospitalizations, all centres had low in-hospital mortality. We consider this as an indication of good clinical practice in the three studied centres and possibly due to the frequent use of non-invasive ventilation. PMID- 20363606 TI - Predictors of mortality in hospitalized patients with acute exacerbation of bronchiectasis. AB - BACKGROUND: In-hospital and long term outcomes of patients admitted to the hospital for acute exacerbation of bronchiectasis (AEB) has been evaluated in only a limited fashion. The resulting debilitation after an AEB can increase mortality. This study aims to evaluate the factors associated with mortality in patients admitted with an acute exacerbation of bronchiectasis (AEB). METHODS: All charts of the patients admitted between 2003 and 2006 with an AEB were reviewed through an electronic database. Demographics, sputum cultures, pulmonary functions tests and other factors associated with long-term mortality were examined. The social security death index was used to determine long term mortality (http://ssdi.genealogy.rootsweb.com). RESULTS: Forty-three patients (13 men and 30 women) with a mean age of 71.8+/-11.8 were studied. The hospital mortality was 9% and one-year mortality was 30% with a median survival of 46.6 months. Variables associated with mortality were male gender (female vs. male (HR), 0.36; (CI), 0.14-0.98; p=0.045), use of systemic steroids (with vs. without steroids HR, 3.12; CI 1.08-9.02; p=0.036), decreased FEV(1.0)% predicted (HR, 0.96; CI 0.92-0.999; p=0.042), elevated creatinine (HR, 2.36; CI 1.093-5.10; p=0.029), history of smoking (HR, 0.283; CI 0.097-0.825; p=0.021), and mechanical ventilation (HR, 66.011; CI 6.64-656.76; p=0.0004). CONCLUSIONS: Male gender, elevated creatinine, decreased FEV(1.0)% predicted, mechanical ventilation, history of smoking, and acute use of systemic steroids during the hospitalization were associated with an increased risk of mortality. PMID- 20363604 TI - Inflammatory cytokines as a third signal for T cell activation. AB - CD8 T cells require a third signal, along with Ag and costimulation, to make a productive response and avoid death and/or tolerance induction. Recent studies indicate that IL-12 and Type I IFN (IFNalpha/beta) are the major sources of signal 3 in a variety of responses, and that the two cytokines stimulate a common regulatory program involving altered expression of about 350 genes. Signal 3 driven chromatin remodeling is likely to play a major role in this regulation. Although less well studied, there is emerging evidence that CD4 T cells may also require a 'third signal' for a productive response and that IL-1 can provide this signal. Signal 3 cytokines can replace adjuvants in supporting in vivo T cell responses to peptide and protein antigens, and a better understanding of their activities and mechanisms should contribute to more rational design of vaccines. PMID- 20363608 TI - Telomerase activity and serum levels of p53 protein as prognostic factors of survival in patients with advanced non-small cell lung cancer. AB - PURPOSE: Evaluation of relationships between survival time of patients with advanced, non-resectable non-small cell lung cancer (NSCLC) and telomerase activity in aspirates, collected from primary lung tumours, and serum p53 protein levels. MATERIAL AND METHODS: The study group consisted of 52 patients with advanced (stage IIIB and IV) non-small cell lung cancer. In all of them, transthoracic fine-needle biopsy (TFNB) of focal pulmonary lesion was performed. The aspirates were subjected to telomerase activity by the PCR-ELISA PLUS method and serum levels of p53 protein were determined by the ELISA method. Additionally, clinical advancement of cancer and the time period of survival were assessed in the studied group. Kaplan-Meyer method and Cox analysis were used for statistical evaluation of survival prognosis. RESULTS: Increased telomerase activity was observed in 42 (81%) of the patients with non-resectable non-small cell lung cancer. Elevated concentrations of serum p53 protein were found in 28 (54%) of the participants. The following death rates were noted during the entire study period: twenty-three (23) (62%), out of 37 patients with increased telomerase activity, 7 (47%), out of 15 without detectable telomerase activity in primary lung tumour, 16 (57%), out of 28 subjects with increased serum levels of p53 protein and 14 (58%), out of 24 with no increased serum levels of p53. A significant relationship was observed in Cox hazard analysis between the time of survival and telomerase activity, while no such relationship was observed between the survival time period and serum p53 protein levels or sex, age, primary lung tumour size, lymph node status or development of distant metastases. CONCLUSION: Telomerase activity in advanced primary non-small cell lung cancer is a better predictor of patients' survival than serum levels of p53 protein. The assessment of telomerase activity supplements in the prognosis of survival in the course of non-resectable NSCLC. PMID- 20363609 TI - Interplay between DNA replication and gene expression: a harmonious coexistence. AB - Multicellular organisms have evolved highly sophisticated machinery to that their genomes are accurately duplicated and that the various gene expression programs are established correctly. Recent large-scale studies have shed light on how these fundamental processes interact. Although the machinery mediating these processes share similar cis-regulatory elements, they are not strictly coregulated. Furthermore, studies of the replisome show that highly transcribed genes present a major obstacle to its operation. Further studies will be needed to identify key regulators of the spatio-temporal program of DNA replication, for the elucidation of the complex interplay between replication and transcription. PMID- 20363610 TI - Ultrasensitive and selective detection of mercury(II) in aqueous solution by polymerase assisted fluorescence amplification. AB - A new label-free Hg(2+) ions assay with polymerase assisted fluorescence amplification was developed. In this approach, a single strand template probe containing a mercury ion recognition sequence (MRS) which is composed of two thymine (T)-rich functional areas separated by a spacer of random bases was designed. In this sensing system, upon addition of Hg(2+) ions, the complexation of Hg(2+) ions with the MRS yielded a hairpin complex through T-Hg(2+)-T base pairs. The formation of the hairpin structure initiated the replication of the template probe in the presence of the polymerase/dNTPs. Then the replication products of long duplex DNA probes were stained with a sensitive reagent SYBR Green I (SG). As a result, SG integrated with the duplex DNA probes and induced a distinguishable fluorescence enhancement in response to Hg(2+) ions triggered replication reaction. Due to the fluorescence amplification step, this method exerted substantial enhancement in sensitivity and could be used for rapid and selective detection of low picomolar Hg(2+) ions. It is expected that this cost effective fluorescence sensor might hold considerable potential in the detection of Hg(2+) ions in real environmental samples. PMID- 20363611 TI - Development of a disposable amperometric biosensor for salicylate based on a plastic electrochemical microcell. AB - The use of an amperometric biosensor for rapid salicylate determination in blood is described. Photolitography was used to make gold electrodes on a polyester film. The plastic microcell was characterized using cyclic voltammetry to demonstrate the electrochemical performance of the system. The biosensor was constructed by immobilizing salicylate hydroxylase onto the working electrode of the plastic electrochemical microcell. The optimized working conditions were 0.1 mol L(-1) phosphate buffer at pH 7.6 with 0.5 mmol L(-1) of NADH and 300 mV vs. Au as the applied potential. The resulting biosensor exhibited a high sensitivity (97.4 nA/mmol L(-1) salicylate) and an adequate linear response range (1.2x10(-4) to 1.0x10(-3)mol(-1)). The biosensor performance was verified by determining salicylate in spiked blood samples and the results were statistically equivalent to the values obtained from the standard Trinder spectrophotometric method, with a 95% confidence level. This study shows the potential development of a portable, inexpensive and disposable device for point-of-care monitoring. PMID- 20363612 TI - More from less: plant growth under limited water. AB - When subjected to abiotic stresses, plants actively re-program their growth by modulating both cell division and cell expansion. Growth decreases rapidly upon stress onset but it recovers and adapts once stress conditions become stable. Here, we review recent advances in understanding the mechanisms underlying both stress-induced growth repression and adaptation with an emphasis on drought and leaf growth and we briefly discuss how this knowledge can be translated into crops. It is now clear that stress response of growing and mature leaves is distinct and should be studied separately. Both cell proliferation and expansion are regulated by common signaling pathways involving gibberellins and DELLA proteins while down stream effector genes are stage specific. PMID- 20363613 TI - Preliminary studies for a CBCT imaging protocol for offline organ motion analysis: registration software validation and CTDI measurements. AB - Cone-beam X-ray volumetric imaging in the treatment room, allows online correction of set-up errors and offline assessment of residual set-up errors and organ motion. In this study the registration algorithm of the X-ray volume imaging software (XVI, Elekta, Crawley, United Kingdom), which manages a commercial cone-beam computed tomography (CBCT)-based positioning system, has been tested using a homemade and an anthropomorphic phantom to: (1) assess its performance in detecting known translational and rotational set-up errors and (2) transfer the transformation matrix of its registrations into a commercial treatment planning system (TPS) for offline organ motion analysis. Furthermore, CBCT dose index has been measured for a particular site (prostate: 120 kV, 1028.8 mAs, approximately 640 frames) using a standard Perspex cylindrical body phantom (diameter 32 cm, length 15 cm) and a 10-cm-long pencil ionization chamber. We have found that known displacements were correctly calculated by the registration software to within 1.3 mm and 0.4 degrees . For the anthropomorphic phantom, only translational displacements have been considered. Both studies have shown errors within the intrinsic uncertainty of our system for translational displacements (estimated as 0.87 mm) and rotational displacements (estimated as 0.22 degrees ). The resulting table translations proposed by the system to correct the displacements were also checked with portal images and found to place the isocenter of the plan on the linac isocenter within an error of 1 mm, which is the dimension of the spherical lead marker inserted at the center of the homemade phantom. The registration matrix translated into the TPS image fusion module correctly reproduced the alignment between planning CT scans and CBCT scans. Finally, measurements on the CBCT dose index indicate that CBCT acquisition delivers less dose than conventional CT scans and electronic portal imaging device portals. The registration software was found to be accurate, and its registration matrix can be easily translated into the TPS and a low dose is delivered to the patient during image acquisition. These results can help in designing imaging protocols for offline evaluations. PMID- 20363614 TI - Treatment of nitrate contaminated water using an electrochemical method. AB - Treatment of nitrate contaminated water which is unsuitable for biological removal using an electrochemical method with Fe as a cathode and Ti/IrO(2)-Pt as an anode in an undivided cell was studied. In the absence and presence of 0.50 g/L NaCl, the nitrate-N decreased from 100.0 to 7.2 and 12.9 mg/L in 180 min, respectively, and no ammonia and nitrite by-products were detected in the presence of NaCl. The nitrate reduction rate increased with increasing current density, with the nitrate reduction rate constant k(1) increasing from 0.008 min( 1) (10 mA/cm(2)) to 0.016 min(-1) (60 mA/cm(2)) but decreasing slightly with increasing NaCl concentration. High temperature favoured nitrate reduction and the reaction followed first order kinetics. The combination of the Fe cathode and Ti/IrO(2)-Pt anode was suitable for nitrate reduction between initial pH values 3.0 and 11.0. e.g. k(1)=0.010 min(-1) (initial pH 3.0) and k(1)=0.013 min(-1) (initial pH 11.0). Moreover, the surface of all used cathodes appeared rougher than unused electrodes, which may have increased the nitrate reduction rate (4 6%). PMID- 20363615 TI - Fate of manure phosphorus in a weathered sandy clay loam soil amended with three animal manures. AB - Laboratory incubation was conducted for 120 days to study the fate of phosphorus in poultry (PM), cattle (CM) and goat manures (GM). Phosphorus mineralized from manure was dependent on total P, Al and Fe content. Manures improved P availability in the order: PM>CM>GM; however, the highest amount of P was fixed or immobilized between 10 and 70 days of incubating with CM and GM. Fixation and immobilization of mineralized P from poultry manure was negligible probably due to the high total P and the low amount of Al and Fe. Generally, manure application reduced the ability of the soil to fix P. More than 90% of the manure P was either immobilized or fixed by the soil. The relationship between the amount of P released and time was cubic. Improvement of the C:P ratio of CM and GM would be an option to enhance their agronomic use as fertilizer P source. PMID- 20363616 TI - Microbial production of hyaluronic acid from agricultural resource derivatives. AB - Agricultural resource derivatives (ARDs) such as hydrolysate soy protein concentrate (HSPC), whey protein concentrate (WPC), and cashew apple juice (CAJ) were studied with focus on the production of hyaluronic acid (HA) by Streptococcus zooepidemicus. Supplementation of the media with corn steep liquor (CSL) was also evaluated. Synthetic medium containing glucose and yeast extract was used as control. CAJ was a promising medium for the production of HA. It produced the highest amount of HA (0.89 g L(-1)), similar to that of the control (0.86 g L(-1)). WPC and HSPC media were the most effective for the production of biomass. CSL did not influence the production of HA when HSPC and WPC were used. However, in the synthetic medium it doubled the yield of HA from glucose. The average molecular weight of HA ranged from 10(3) to 10(4)Da for the ARDs and 10(7)Da for the synthetic medium. PMID- 20363617 TI - Kinetic parameters for 17alpha-ethinylestradiol removal by nitrifying activated sludge developed in a membrane bioreactor. AB - The synthetic hormone 17alpha-ethinylestradiol (EE2) is primarily removed in wastewater treatment plants (WWTPs) by sorption, and nitrifying biomass has been shown to be responsible for EE2 biodegradation. Membrane bioreactor (MBR) technology was chosen to develop a community of autotrophic, nitrifying micro organisms and determine kinetic parameters for EE2 biodegradation. Biological inhibition by azide was applied to differentiate sorption from biodegradation. Activated sludge (AS) was acclimated in the MBR to a substrate specific to autotrophic biomass and resulted in an increase in nitrifying activity. Acclimated AS was used to successfully biodegrade EE2 (11% increase in EE2 removal), and the overall removal of EE2 was determined to be 99% (sorption+biodegradation). AS used directly from a WWTP without acclimation removed EE2 only through sorption (88% removal of EE2). Therefore, higher nitrifying activity developed by acclimating AS allowed almost complete removal of EE2. PMID- 20363618 TI - Microbial-growth inhibition during composting of food waste: effects of organic acids. AB - Factorial designs were employed to analyze the inhibitory effects of acetic, butyric, lactic, and propionic acids on composting microorganisms. Compost samples were withdrawn on different days of composting and treated with acids alone and in combination (at 0 and 0.5 mmol/g). Microorganisms were enumerated to determine degree of growth inhibition. Generally, inhibition was more severe on the day when pH decreased rather than on the day when pH started to increase. Butyric or lactic acid alone, and the combination of butyric, lactic, and propionic acids, significantly inhibited thermophilic bacteria. Only 51.0-65.0% of the thermophilic bacteria exist if 0.5 mmol/g of these acids were present in compost. Temperature, microbial populations, and microbial growth phase might cause variation in the inhibitory effects of acids. These findings are useful not only in the study of microorganisms in acidic microenvironments, but also in preventing microbial-growth inhibition by predicting population via a regression model. PMID- 20363619 TI - Influence of particle size on pyrolysis and gasification performance of municipal solid waste in a fixed bed reactor. AB - Pyrolysis and gasification of municipal solid waste (MSW) were carried out in a lab-scale fixed bed reactor in order to evaluate the effects of particle size at different bed temperatures on product yield and composition. The bed temperature was varied from 600 to 900 degrees C and the MSW was separated into three different size fractions (below 5 mm, 50-10 mm and above 10 mm). Particle size and temperature had integrated effects on product yield and composition: higher temperature resulted in higher gas yield with less tar and char, and, at the same temperature, dry gas yield increased with a decrease in particle size, and char and tar yield decreased. The differences due to particle sizes in pyrolysis and gasification performance practically disappeared at the highest temperatures tested. Smaller particle sizes resulted in higher H(2) and CO contents for both pyrolysis and gasification of MSW. Minimizing the size of raw materials is an alternative method to improve the gas quality of MSW pyrolysis and gasification. PMID- 20363620 TI - Anaerobic co-digestion of glycerol and wastewater derived from biodiesel manufacturing. AB - The anaerobic co-digestion of glycerol and wastewater derived from biodiesel manufacturing, in which COD was found to be 1054 and 428 g/L, respectively, was studied in batch laboratory-scale reactors at mesophilic temperature (35 degrees C). Glycerol was acidified with H(3)PO(4) in order to recover the alkaline catalyst employed in the transesterification reaction (KOH) as agricultural fertiliser (potassium phosphates). Wastewater was subjected to an electrocoagulation process in order to reduce its oil content. After mixing, the anaerobic revalorisation of the wastewater was studied employing inoculum substrate ratios ranging from 5.02 to 1.48 g VSS/g COD and organic loading rates of 0.27-0.36 g COD/g VSS d. Biodegradability was found to be around 100%, while the methane yield coefficient was 310 mL CH(4)/g COD removed (1 atm, 25 degrees C). At the equilibrium time, the proportionality between r' and the load was constant, showing 1.55 mL CH(4)/(g VSS g COD h). The results showed that anaerobic co-digestion reduces the clean water and nutrient requirement, with the consequent economical and environmental benefit. PMID- 20363621 TI - Thermodynamics and inhibition studies of lipozyme TL IM in biodiesel production via enzymatic transesterification. AB - In order to characterize enzyme activity and stability corresponding to temperature effects, thermodynamic studies on commercial immobilized lipase have been carried out via enzymatic transesterification. An optimum temperature of 40 degrees C was obtained in the reaction. The decreasing reaction rates beyond the optimum temperature indicated the occurrence of reversible enzyme deactivation. Thermodynamic studies on lipase denaturation exhibited a first-order kinetics pattern, with considerable stability through time shown by the lipase as well. The activation and deactivation energies were 22.15 kJ mol(-1) and 45.18 kJ mol( 1), respectively, implying more energy was required for the irreversible denaturation of the enzyme to occur. At water content of 0.42%, the initial reaction rate and FAME yield displayed optimum values of 3.317 g/L min and 98%, respectively. PMID- 20363622 TI - Efficient whole-cell biotransformation of 5-(hydroxymethyl)furfural into FDCA, 2,5-furandicarboxylic acid. AB - 2,5-furandicarboxylic acid (FDCA) is a promising bio-based platform chemical that may serve as a 'green' substitute for terephthalate in polyesters. Recently, a novel HMF/furfural oxidoreductase from Cupriavidus basilensis HMF14 was identified that converts 5-(hydroxymethyl)furfural (HMF) into FDCA. The hmfH gene encoding this oxidoreductase was introduced into Pseudomonas putida S12 and the resulting whole-cell biocatalyst was employed to produce FDCA from HMF. In fed batch experiments using glycerol as the carbon source, 30.1 g l(-1) of FDCA was produced from HMF at a yield of 97%. FDCA was recovered from the culture broth as a 99.4% pure dry powder, at 76% recovery using acid precipitation and subsequent tetrahydrofuran extraction. PMID- 20363623 TI - Squalenoyl nucleoside monophosphate nanoassemblies: new prodrug strategy for the delivery of nucleotide analogues. AB - 4-(N)-1,1',2-trisnor-squalenoyldideoxycytidine monophosphate (SQddC-MP) and 4-(N) 1,1',2-trisnor-squalenoylgemcitabine monophosphate (SQdFdC-MP) were synthesized using phosphoramidite chemistry. These amphiphilic molecules self-assembled to about hundred nanometers size nanoassemblies in aqueous medium. Nanoassemblies of SQddC-MP displayed significant anti-HIV activity whereas SQdFdC-MP nanoassemblies displayed promising anticancer activity on leukemia cells. These results suggested that squalene conjugate of negatively charged nucleotide analogues efficiently penetrated within cells. Thus, we propose a new prodrug strategy for improved delivery of nucleoside analogues to ameliorate their biological efficacy. PMID- 20363624 TI - Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a). AB - Tricyclic pyrazole tetrazoles which are potent partial agonists of the high affinity niacin receptor, GPR109a, have been discovered and optimized. One of these compounds has proven to be effective at lowering free fatty acids in vitro and in vivo. PMID- 20363625 TI - Identification of a novel series of potent RON receptor tyrosine kinase inhibitors. AB - A novel series of N-(3-fluoro-4-(2-substituted-thieno[3,2-b]pyridin-7 yloxy)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides targeting RON receptor tyrosine kinase was designed and synthesized. SAR study of the series allowed us to identify compounds possessing either inhibitory activity of RON kinase enzyme in the low nanomolar range with low residual activity against the closely related c-Met or potent dual inhibitory activity against RON and c Met, with no significant activity against VEGFR2 in both cases. PMID- 20363626 TI - Synthesis and biological evaluation of combretastatin analogs as cell cycle inhibitors of the G1 to S transition in Saccharomyces cerevisiae. AB - A series of Z and E combretastatin A-4 analogs bearing different substituents (OH, F, NO(2), NH(2), B(OH)(2)) in the 3' position were synthesized. These derivatives and Z and E combretastatin A-1 were analysed by monitoring their ability to inhibit cell growth in Saccharomyces cerevisiae. Combretastatin A-1 (2a), A-4 (2b) and compound 2c were found to inhibit yeast growth. Moreover, combretatstatin A-4 (2b) and compound 2c induced a G1 arrest by affecting the synthesis of Clb5 protein, the principal S-phase cyclin. The G1 arrest is coincident with the activation of the stress activated kinase Snf1. PMID- 20363627 TI - Identification and structure-activity relationship of 8-hydroxy-quinoline-7 carboxylic acid derivatives as inhibitors of Pim-1 kinase. AB - Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apoptosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxy quinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency. PMID- 20363628 TI - Design of environmentally sensitive fluorescent 2'-deoxyguanosine containing arylethynyl moieties: distinction of thymine base by base-discriminating fluorescent (BDF) probe. AB - We have synthesized various substituted 8-arylethynylated 2'-deoxyguanosine derivatives. Among them, acetyl substituted deoxyguanosine analogue 4c showed a remarkable solvent dependent fluorescence property, that is, an intense fluorescence in non-polar solvents but extremely weak fluorescence in polar solvents like methanol. By using solvatofluorochromic deoxyguanosine analogue 4c, we have developed highly thymine (T) selective fluorescent DNA probes that can sense T opposite 4c in a target DNA regardless of the flanking sequences. We were able to demonstrate that 4c can be used as a T specific base-discriminating fluorescent (BDF) nucleoside in homogeneous fluorescence assay. PMID- 20363629 TI - Discovery and structural optimization of pyrazole derivatives as novel inhibitors of Cdc25B. AB - Structural optimization and preliminary structure-activity relationship studies of a series of N-substituted maleimide fused-pyrazole analogues with Cdc25B inhibitory activity, starting from a high-throughput screening hit, are illustrated. A simplified 3,5-diacyl pyrazole analogue was obtained as the most potent compound (118, IC(50)=0.12 microM) with a 270-fold increase in potency. PMID- 20363630 TI - Use of gait sandals for measuring rearfoot and shank motion during running. AB - Gait sandals may be used as an alternative to shoes in gait analysis. However, their similarity to running shoes remains unclear. This study aimed to compare rearfoot and shank kinematics between barefoot, running shoes and gait sandal conditions during running. We hypothesised that gait sandals would more closely replicate the kinematics seen when wearing running shoes than when barefoot. Rearfoot and shank kinematics were measured in 14 male participants as they ran in three footwear conditions (barefoot, gait sandals and running shoes) at 3.5m/s. Both barefoot and gait sandals resulted in greater peak rearfoot eversion compared to running shoes. Gait sandals were similar to running shoes for all other variables. These findings suggest that gait sandals can be used in place of running shoes during gait analysis to study rearfoot and shank kinematics. PMID- 20363631 TI - Chaperones and multitasking proteins in the nucleolus: networking together for survival? AB - The nucleolus has emerged as a key player that regulates cell growth, survival and the recovery from stress. Progress in proteomics made it possible to sequence the nucleolar proteome under different physiological conditions. Together with other research, this work revealed the presence of multiple chaperones and co chaperones in the nucleolus. Molecular chaperones are components of a larger network that promotes protein homeostasis, thereby providing continuous adaptation to a changing environment. Recent studies suggest that the cellular chaperone network is divided into individual branches which orchestrate specific functions. Input from separate branches is then combined to 'fine-tune' the cellular proteostasis network. Based on the latest developments in nucleolar and chaperone biology, we speculate that a unique network comprising chaperones, co chaperones and multitasking proteins is located in nucleoli. This network supports and regulates fundamental biological processes, including ribosome biogenesis, cell signaling, and the stress response. PMID- 20363632 TI - Total synthesis of (+)-crocacin C. AB - Two approaches toward the total synthesis of cytotoxic polyketide natural product (+)-crocacin C (1) are described. The first approach, which was ultimately unsuccessful, was replaced altogether with a second that afforded target 1 in 10 linear steps from commercially available Evans' chiral propionimide (5% overall yield). No protecting groups were utilized in the total synthesis of 1. PMID- 20363633 TI - Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation. AB - A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate. PMID- 20363634 TI - Design, synthesis, biological evaluation and computational investigation of novel inhibitors of dihydrofolate reductase of opportunistic pathogens. AB - The present work deals with design, synthesis and biological evaluation of novel, diverse compounds as potential inhibitors of dihydrofolate reductase (DHFR) from opportunistic microorganisms; Pneumocystis carinii (pc), Toxoplasma gondii (tg) and Mycobacterium avium (ma). A set of 14 structurally diverse compounds were designed with varying key pharmacophoric features of DHFR inhibitors, bulky distal substitutions and different bridges joining the distal part and 2,4 diaminopyrimidine nucleus. The designed compounds were synthesized and evaluated in enzyme assay against pc, tg and ma DHFR. The rat liver (rl) DHFR was used as mammalian standard. As the next logical step of the project, flexible molecular docking studies were carried out to predict the binding modes of these compounds in pcDHFR active site and the obtained docked poses were post processed using MM GBSA protocol for prediction of relative binding affinity. The predicted binding modes were able to rationalize the experimental results in most cases. Of particular interest, both the docking scores and MM-GBSA predicted Delta G(bind) were able to distinguish between the active and low active compounds. Furthermore, good correlation coefficient of 0.797 was obtained between the IC(50) values and MM-GBSA predicted Delta G(bind). Taken together, the current work provides not only a novel scaffold for further optimization of DHFR inhibitors but also an understanding of the specific interactions of inhibitors with DHFR and structural modifications that improve selectivity. PMID- 20363635 TI - Identification of serotonin 5-HT1A receptor partial agonists in ginger. AB - Animal studies suggest that ginger (Zingiber officinale Roscoe) reduces anxiety. In this study, bioactivity-guided fractionation of a ginger extract identified nine compounds that interact with the human serotonin 5-HT(1A) receptor with significant to moderate binding affinities (K(i)=3-20 microM). [(35)S]-GTP gamma S assays indicated that 10-shogaol, 1-dehydro-6-gingerdione, and particularly the whole lipophilic ginger extract (K(i)=11.6 microg/ml) partially activate the 5 HT(1A) receptor (20-60% of maximal activation). In addition, the intestinal absorption of gingerols and shogaols was simulated and their interactions with P glycoprotein were measured, suggesting a favourable pharmacokinetic profile for the 5-HT(1A) active compounds. PMID- 20363636 TI - Prenylated pterocarpans as bacterial neuraminidase inhibitors. AB - During the course of a neuraminidase inhibitor screening program on natural products, four new (6, 8, 11, and 12) and eleven known (1-5, 7, 9-10, and 13-15) pterocarpan derivatives were isolated as active principles from the EtOAc extract of the stem bark of Erythrina abyssinica. Their structures were identified by spectroscopic data analyses. All isolates exhibited significant inhibitory effects on the neuraminidases from Clostridium perfringens and Vibrio cholerae with IC(50) values ranging from 1.32 to 77.10 microM and 0.35 to 77.73 microM, respectively. The isolates (1-3, 5-8, 10, and 13-15), which possessed noncompetitive inhibition modes in kinetic studies, showed stronger activity against C. perfringens neuraminidase (IC(50) 1.32-19.82 microM) than quercetin (IC(50) 25.34 microM), which was used as the positive control. In contrast, compounds 4 and 9 behaved as competitive inhibitors and were displayed less effective (IC(50) 26.39-33.55 microM). Furthermore, calopocarpine, as a neuraminidase inhibitor, produced a decrease of V. cholerae adhesion to the host cell. Overall, these results suggest that neuraminidase inhibitors can be used in the development of new treatments to combat infectious diseases. PMID- 20363637 TI - The anti-cancer, anti-inflammatory and tuberculostatic activities of a series of 6,7-substituted-5,8-quinolinequinones. AB - A variety of 6,7-substituted-5,8-quinolinequinones were synthesised and assessed for their anti-tumour and anti-inflammatory activities, and their ability to inhibit the growth of Mycobacterium bovis BCG. In particular, the introduction of a sulfur group at the 7-position of the quinolinequinone led to the discovery of two compounds, 6-methylamino-7-methylsulfanyl-5,8-quinolinequinone (10a) and 6 amino-7-methylsulfonyl-5,8-quinolinequinone (12), that exhibited selectivity for leukemic cells over T-cells, a highly desirable property for an anti-cancer drug. A number of anti-inflammatory (AI) compounds were also identified, with 6,7-bis methylsulfanyl-5,8-quinolinequinone (18a) exhibiting the highest AI activity (0.11 microM), while 6,7-dichloro-5,8-quinolinequinone (7a), 6,7-dichloro-2 methyl-5,8-quinolinequinone (7b), and 6,7-bis-phenylsulfanyl-quinoline-5,8-diol (19) also exhibited good AI activity and specificity. Several quinolinequinone TB drug candidates were identified. Of these, 6-amino-7-chloro-5,8-quinolinequinone (11) and 6-amino-7-methanesulfinyl-5,8-quinolinequinone (14), exhibited low MICs (1.56-3.13 microg/mL) for the 100% growth inhibition of M. Bovis BCG. Some general trends pertaining to the functional group substitution of the quinolinequinone core and biological activity were also identified. PMID- 20363638 TI - Sugar-based peptidomimetics as potential inhibitors of the vascular endothelium growth factor binding to neuropilin-1. AB - Neuropilin-1 (NRP-1) is a co-receptor of VEGFR(165) and molecules interfering with VEGF(165) binding to NRP-1 seem to be promising candidates as new angiogenesis modulators. Based on the minimal four amino acid sequence of peptidic ligands known to bind NRP-1, we describe here the design, synthesis and biological evaluation of series of original sugar-based peptidomimetics using a C glycosyl compound, derived from d-gulonolactone, as a scaffold, which was functionalized with side chains of the amino-acids arginine, and tryptophane or threonine. At 100 microM, all compounds exhibited a weak affinity for NRP-1, the most efficient being the bis-guanidinylated compound 32 (IC(50)=92 microM) which could be considered as a new NRP-1 non-peptidic ligand. PMID- 20363639 TI - Structural quantification of wood fibre surfaces--morphological effects of pulping and enzymatic treatment. AB - Wood fibres have been utilized by our society as an important component of paper products and are presently gaining more interest as reinforcement in composite materials. During the last decades biochemical treatments have also found applications in the processing of wood fibres. The chemical, mechanical and biochemical treatments affect the morphology of the fibre wall structure at the micro- and nano-level. In this study, we present a modern approach where field emission SEM (FE-SEM) and relevant computerized image analysis are applied to quantify the fibre wall characteristics. Details such as surface roughness and texture of the fibre walls are quantified objectively. Global polar plots are generated, which are considered to represent the fingerprint of a given pulp. The approach offers a novel perspective in the characterisation of surface structures, moving forward from performing subjective evaluations to performing objective quantifications of wood pulp fibre surfaces. PMID- 20363640 TI - Effect of gamma-irradiation on the biology and ultrastructure of haemocytes of greater wax moth, Galleria mellonella (L.) (Lepidoptera: Galleridae). AB - This study was carried out on fully grown pupae of greater wax moth, Galleria mellonella L., gamma-irradiated to 100, 150, 300 and 400Gy. The four doses given to male parents in the F(1) generation decreased the average number of eggs per mated female, the percentage of egg hatching and the percentage of mating in both the male and female lines; the effects increased with the dose. Dose dependence of the reduction in the fecundity and the percentage of egg hatching among the female line pairings (female descendants of irradiated parental male pupae) was more significant than among the male line pairings (male descendants of irradiated parental male pupae). We also examined morphological changes in the irradiated blood cells using transmission electron microscopy (TEM). Vacuolization of the cytoplasm, disorganization and swelling of mitochondria were found. PMID- 20363641 TI - Expression profiling of various genes during the fruit development and ripening of mango. AB - Mango (Mangifera indica L. cv. Alphonso) development and ripening are the programmed processes; conventional indices and volatile markers help to determine agronomically important stages of fruit life (fruit-setting, harvesting maturity and ripening climacteric). However, more and precise markers are required to understand this programming; apparently, fruit's transcriptome can be a good source of such markers. Therefore, we isolated 18 genes related to the physiology and biochemistry of the fruit and profiled their expression in developing and ripening fruits, flowers and leaves of mango using relative quantitation PCR. In most of the tissues, genes related to primary metabolism, abiotic stress, ethylene response and protein turnover showed high expression as compared to that of the genes related to flavor production. Metallothionin and/or ethylene response transcription factor showed highest level of transcript abundance in all the tissues. Expressions of mono- and sesquiterpene synthases and 14-3-3 lowered during ripening; whereas, that of lipoxygenase, ethylene-response factor and ubiquitin-protein ligase increased during ripening. Based on these expression profiles, flower showed better positive correlation with developing and ripening fruits than leaf. Most of the genes showed their least expression on the second day of harvest, suggesting that harvesting signals significantly affect the fruit metabolism. Important stages in the fruit life were clearly indicated by the significant changes in the expression levels of various genes. These indications complemented those from the previous analyses of fruit development, ripening and volatile emission, revealing the harmony between physiological, biochemical and molecular activities of the fruit. PMID- 20363642 TI - Changes in content of free, conjugated and bound polyamines and osmotic adjustment in adaptation of vetiver grass to water deficit. AB - Osmotic adjustment and alteration of polyamines (PAs) have been suggested to play roles in plant adaptation to water deficit/drought stress. In this study, the changes in cell intactness, photosynthesis, compatible solutes and PAs [including putrescine (Put), spermidine (Spd) and spermine (Spm) each in free, conjugated and bound forms] were investigated in leaves of vetiver grass exposed to different intensity of water deficit stress and subsequent rewatering. The results showed that, when vetiver grass was exposed to the moderate (20% and 40% PEG-6000 solutions) and severe (60% PEG solution) water deficit for 6days, the plant injury degree (expressed as the parameters of plant growth, cell membrane integrity, water relations and photosynthesis) increased and contents of free and conjugated Put decreased with the rise of PEG concentration. Under the moderate water deficit, the plants could survive by the reduced osmotic potential (psi(s)), increased free and conjugated Spd and Spm in leaves. After subsequent rewatering, the osmotic balance was re-established, most of the above investigated physiological parameters were fully or partly recovered to the control levels. However, it was not the case for the severely-stressed and rewatering plants. It indicates that, vetiver grass can cope well with the moderate water deficit/drought stress by using the strategies of osmotic adjustment and maintenance of total contents of free, conjugated and bound PAs in leaves. PMID- 20363643 TI - Targeted therapies in non-small-cell lung cancer (NSCLC): how to proceed to aim at the good target? PMID- 20363644 TI - Interleukin-8 -251 A/T gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiological studies. AB - Previous studies suggested the relationship between interleukin (IL)-8 -251 A/T gene polymorphism and risk of gastric cancer (GC). However, the currently available results were not consistent. The present study aimed to quantitatively analyse this association using a meta-analysis. Published literature from PubMed, EMBASE and CNKI (China Knowledge Resource Integrated Database) were retrieved. Twelve case-control studies with 3012 cases of GC and 3893 controls were included. Overall, IL-8 -251 A/T polymorphism was not associated with the risk of GC. However, when stratified for ethnicity/country, the results showed that A allele carriers had an increased risk of GC while T allele carriers had a decreased risk of GC in Korean people. When stratified for Helicobacter pylori infection, the results showed that A allele carriers with H. pylori infection had an increased risk of GC while T allele carriers with or without H. pylori infection had a decreased risk of GC. When stratified for tumor location and histological type (Lauren's classification), A allele carriers had an increased risk of intestinal- and diffuse-type of GC and non-cardia cancer, while T allele carriers had a decreased risk of intestinal- and diffuse-type of GC and non cardia cancer. These results suggest that overall IL-8 -251 A/T gene polymorphism is not associated with the risk of GC and the association may be varied according to histological type, tumor location, H. pylori infection and ethnicity/country. More well-designed studies based on larger population are needed to confirm our results and further evaluate the association between IL-8 -251 A/T gene polymorphism and gastric cancer. PMID- 20363645 TI - Measuring internal energy deposition in collisional activation using hydrated ion nanocalorimetry to obtain peptide dissociation energies and entropies. AB - The internal energy deposited in both on- and off-resonance collisional activation in Fourier transform ion cyclotron resonance mass spectrometry is measured with ion nanocalorimetry and is used to obtain information about the dissociation energy and entropy of a protonated peptide. Activation of Na(+)(H(2)O)(30) results in sequential loss of water molecules, and the internal energy of the activated ion can be obtained from the abundances of the product ions. Information about internal energy deposition in on-resonance collisional activation of protonated peptides is inferred from dissociation data obtained under identical conditions for hydrated ions that have similar m/z and degrees-of freedom. From experimental internal energy deposition curves and Rice-Ramsperger Kassel-Marcus (RRKM) theory, dissociation data as a function of collision energy for protonated leucine enkephalin, which has a comparable m/z and degrees-of freedom as Na(+)(H(2)O)(30), are modeled. The threshold dissociation energies and entropies are correlated for data acquired at a single time point, resulting in a relatively wide range of threshold dissociation energies (1.1 to 1.7 eV) that can fit these data. However, this range of values could be significantly reduced by fitting data acquired at different dissociation times. By measuring the internal energy of an activated ion, the number of fitting parameters necessary to obtain information about the dissociation parameters by modeling these data is reduced and could result in improved accuracy for such methods. PMID- 20363646 TI - Top-down mass spectrometry for sequencing of larger (up to 61 nt) RNA by CAD and EDD. AB - We have studied the effect of solution additives on hydrolysis and charge state distribution in ESI MS of RNA. Lower and higher charge state ions can be electrosprayed from solutions containing 25 mM piperidine/25 mM imidazole and 1% vol. triethylamine, respectively, with base-catalyzed hydrolysis rates that are sufficiently slow to perform MS/MS experiments. These lower and higher charge state ions are suitable as precursors for CAD and EDD, respectively. We demonstrate nearly complete sequence coverage for 61 nt RNA dissociated by CAD, and 34 nt RNA dissociated by EDD, and suggest a mechanism for backbone fragmentation in EDD of RNA. PMID- 20363647 TI - Review of the 22nd Sanibel Conference on mass spectrometry: from structural biology to drug discovery: new roles for mass spectrometry of nucleic acids. PMID- 20363650 TI - Mindfulness meditation improves cognition: evidence of brief mental training. AB - Although research has found that long-term mindfulness meditation practice promotes executive functioning and the ability to sustain attention, the effects of brief mindfulness meditation training have not been fully explored. We examined whether brief meditation training affects cognition and mood when compared to an active control group. After four sessions of either meditation training or listening to a recorded book, participants with no prior meditation experience were assessed with measures of mood, verbal fluency, visual coding, and working memory. Both interventions were effective at improving mood but only brief meditation training reduced fatigue, anxiety, and increased mindfulness. Moreover, brief mindfulness training significantly improved visuo-spatial processing, working memory, and executive functioning. Our findings suggest that 4days of meditation training can enhance the ability to sustain attention; benefits that have previously been reported with long-term meditators. PMID- 20363648 TI - Mass spectrometry and the amyloid problem--how far can we go in the gas phase? AB - A number of proteins are capable of converting from their soluble, monomeric form into highly-ordered, insoluble aggregates known as amyloid fibrils. In vivo, these fibrils, which accumulate in organs and tissues, are associated with a wide range of amyloid diseases for which there are currently no therapeutic solutions. The molecular details of the pathway from native monomer through oligomeric intermediates to the final amyloid fibril remain a challenging enigma. Over the past few years, mass spectrometry has been applied to investigate the various stages of amyloid fibril formation, and this report summarizes the key steps achieved to date. PMID- 20363651 TI - Providing care to transgender persons: a clinical approach to primary care, hormones, and HIV management. AB - Transgender (TG) persons have had historically difficult interactions with health care providers, leading to limited care and risks for a broad spectrum of health problems. This is of particular concern for TG persons with or at risk for HIV infection. This article discusses care providers' roles in establishing TG friendly clinical care sites; conducting appropriate and thorough physical examinations for TG patients; managing hormones, especially in conjunction with antiretroviral therapy; and engaging TG persons in education about prevention and treatment of HIV. PMID- 20363652 TI - Quantitative somatosensory testing of subjects with chronic post-traumatic headache: implications on its mechanisms. AB - BACKGROUND: Chronic headache is one of the most prominent symptoms among subjects with traumatic head injury (THI). Despite the relatively high prevalence of chronic post-traumatic headache (CPTHA) and its enormous effect on the already poor quality of life of subjects with THI, its mechanisms has not been studied in depth. OBJECTIVE: To conducted quantitative somatosensory testing in THI subjects with and without chronic post-traumatic headache (CPTHA) in order to shed light on the yet, unknown pathophysiology of CPTHA. METHODS: THI subjects with and without CPTHA and healthy controls underwent thermal and mechanical threshold measurements in painful and pain-free regions in the head and in their hands (a remote pain-free region) and filled out and the post-traumatic stress disorder (PTSD) inventory. In addition, the THI and CPTHA filled out the Mc'Gill pain questionnaire (MPQ). RESULTS: THI subjects with CPTHA had significantly higher thermal thresholds in both the head and hand indicating central damage to the pain and temperature system and in addition, a significantly lower pressure-pain threshold in the head as well as more severe PTSD symptomatology than the pain free THI subjects and healthy controls. CONCLUSIONS: The sensory profile of subjects with CPTHA suggests that CPTHA may be a form of central pain. The cranial mechanical hyperalgesia may originate from peripheral tissue damage accompanying the THI. Psychological factors may contribute to the development, and maintenance of CPTHA in susceptible individuals. PMID- 20363653 TI - Comparison of daily and weekly retrospectively reported pain intensity in patients with localized and generalized musculoskeletal pain. AB - The purpose of the study was to compare daily and weekly recalled pain intensity over time and their correspondence with real-time pain intensity in patients with localized (LP) and generalized (GP) musculoskeletal pain. Daily recalled pain, averaged over seven consecutive days, and weekly recalled pain at day 8 were recorded on 100 mm visual analogue scales monthly over 4 months for 40 LP and 50 GP patients. Multiple real-time pain ratings on numerical rating scales (0-10) were averaged over the week for 23 LP and 33 GP patients in Month 4. Reliability was assessed using the intraclass correlation coefficients (ICC) and the standard deviations of the repeated measurements. Daily pain ratings were lower than weekly ratings across the 4-month period. Reliability was lower for weekly than for daily recalled pain in the GP group, and lower than in the LP group. These results were independent of the magnitude of pain intensity. No difference was found between daily recalled and real-time ratings. The ICC was higher between daily and real-time ratings than between weekly and real-time ratings in Month 4. Weekly ratings were higher than real-time ratings in the GP group, and the overestimation increased with increasing pain intensity. The results of the present study indicated that reliability was improved by using ratings of daily recalled pain averaged over a week rather than single ratings of weekly recalled pain in subjects with localized or generalized pain. Weekly recalled pain was overestimated in subjects exhibiting generalized pain and high pain intensity. PMID- 20363654 TI - 'Snap-shot' velocity vector mapping using echo-planar imaging. AB - A 'snap-shot' ultra-fast MRI velocimetry technique based upon the echo-planar imaging (EPI) pulse sequence is presented. The new technique is an extension of the GERVAIS pulse sequence previously developed by Sederman et al. (2004) and is capable of acquiring both reference and velocity encoded phase maps following a single excitation for generation of three-component velocity vectors in under 125 ms. This approach allows velocity images of systems with a dynamic, non-periodic geometry to be obtained by MRI. The technique proved to be accurate within 5% error by comparison with Poiseuille flow in a pipe and for the transverse plane flow field in a Couette cell. It was further applied to obtain the velocity field around an impeller in a stirred vessel; an unsteady yet periodic system which otherwise could only be studied by triggered acquisitions. Good agreement was evident between the present technique and triggered conventional velocity encoded pulse sequences. Finally, new experimental data attainable only by the new sequence is demonstrated as the flow field within a mobile droplet of oil is captured as it rises through a column of water. The technique promises to be highly useful in velocimetric measurements of dynamic, non-periodic systems, and in particular for the characterisation of multiphase flow systems. PMID- 20363656 TI - Elevated hydroxyacylcarnitines in a carrier of LCHAD deficiency during acute liver disease of pregnancy - a common feature of the pregnancy complication? AB - Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a mitochondrial fatty acid beta-oxidation defect characterized by accumulation of long-chain hydroxyacylcarnitine intermediates and female carriers of this disorder are in risk for pregnancy complications. We found elevated blood long-chain hydroxyacylcarnitine species in a carrier of LCHAD deficiency at 31weeks of pregnancy with a LCHAD deficient fetus during acute fatty liver of pregnancy-like liver involvement, but had been within the normal range at 25weeks of pregnancy. This finding supports the hypothesis of acylcarnitine accumulation in pathogenesis of AFLP in carriers of LCHAD and MTP deficiencies. PMID- 20363655 TI - Low expression of long-chain acyl-CoA dehydrogenase in human skeletal muscle. AB - PURPOSE: Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial flavoenzyme thought to be one of the major enzymes responsible for the first step of long chain fatty acid (LCFA) beta-oxidation. Surprisingly, recent studies have shown LCAD is hardly detectable in human tissues such as liver and heart. Skeletal muscle is the largest organ in the body in terms of mass, and accounts for the majority of LCFA oxidation, especially during exercise. The purpose of this study was to investigate the expression levels of LCAD in human skeletal muscle. METHODS: Muscle biopsies were obtained from the vastus lateralis of healthy athletic men and women, and examined for mRNA abundance, protein content, and enzyme activity of LCAD. We compared LCAD content with that of very-long chain acyl-CoA dehydrogenase (VLCAD) and medium chain acyl-CoA dehydrogenase (MCAD); two mitochondrial beta-oxidation enzymes that have overlapping chain-length specificity to that of LCAD. LCAD protein content and enzyme activity were also examined in enriched mitochondrial protein fractions. As controls, LCAD presence in skeletal muscle was compared to human heart, liver, and mouse skeletal muscle. RESULTS: The mRNA presence of LCAD in human skeletal muscle is significantly less than VLCAD and MCAD (0.08+/-0.01 vs 7.3+/-0.5 vs 2.4+/-0.2 respectively, P5 and 49.6% of them were classified as being at high risk of having sleep apnea with both questionnaires. Being in the high-risk group with the self reported Berlin questionnaire predicted an RDI>15 with a sensitivity of 0.76 and a specificity of 0.61 versus a sensitivity of 0.82 and a specificity of 0.63 with the bed-partner Berlin questionnaire. Being in the high-risk group with the self reported Berlin questionnaire predicted an RDI>30 with a sensitivity of 0.71 and a specificity of 0.53 versus a sensitivity of 0.79 and a specificity of 0.54 with the bed-partner Berlin questionnaire. CONCLUSIONS: The bed-partner Berlin questionnaire predicts an RDI>15 with a better sensitivity and specificity than the original questionnaire. It could, therefore, be used in bed partners of patients suspected of obstructive sleep apnea syndrome who cannot fill in the self-reported Berlin questionnaire. PMID- 20363670 TI - Prevalence and cost of insomnia in a state Medicaid fee-for-service population based on diagnostic codes and prescription utilization. AB - OBJECTIVES: The aims of this research were to estimate prevalence of insomnia, describe the utilization patterns of physician office services and prescription medications for insomnia, and estimate related costs in a Medicaid population. METHODS: A cross-sectional descriptive analysis using data from the West Virginia (WV) Medicaid fee-for-service paid claims records for the year 2003 was conducted. Recipients with a diagnosis related to insomnia or a prescription claim for an FDA-approved drug for insomnia or trazodone were selected as the study sample. Costs were from the perspective of WV Medicaid. RESULTS: The overall prevalence of insomnia was 74.3 per 1000 recipients. Adults 45-64years of age, females, and whites had the highest prevalence and office visit rates for insomnia among demographic groups. A majority of dollars spent on insomnia treatment was for prescription drugs. Zolpidem and trazodone accounted for 88% of prescription claims; however, 84% of the total dollars paid for prescriptions was for zolpidem. CONCLUSIONS: Among the WV Medicaid population, rates of insomnia and office visit use for insomnia varied by demographic groups. There was greater use of zolpidem and trazodone than benzodiazepine drugs. This study provides baseline estimates that can be used for ongoing surveillance of insomnia. PMID- 20363671 TI - A new model of care for familial hypercholesterolaemia from Western Australia: closing a major gap in preventive cardiology. AB - Familial hypercholesterolaemia (FH) is the most common monogenic cause of premature coronary artery disease. FH remains underdiagnosed and inadequately treated, with no national strategies for dealing with the problem. We report an executive summary of a comprehensive model of care for FH developed in Western Australia. PMID- 20363672 TI - Cerebral malaria: in praise of epistemes. PMID- 20363673 TI - Synthesis of thermo-sensitive copolymer with affinity butyl ligand and its application in lipase purification. AB - In this study, thermo-sensitive N-alkyl substituted polyacrylamide polymer P(NNB) was synthesized by using N-hydroxymethyl acrylamide(NHAM), N-isopropyl acrylamide (NIPA) and butyl acrylate (BA) as monomers, and its low critical solution temperature (LCST) was controlled to be 28 degrees C. The recovery of the thermo sensitive polymer was over 98%. Butanol as a hydrophobic ligand was covalently attached onto polymer P(NNB) and butyl ligand density was 80 micromol g(-1) polymer. The affinity polymer was used for purification of lipase from crude material. Optimized condition was pH 7.0, 35 degrees C adsorption temperature, 120 min adsorption time and 0.5 mg ml(-1) initial concentration of lipase. The adsorption isotherm accords with a typical Langmuir isotherm. The maximum adsorption capacity (Q(m)) of the affinity polymer for lipase was 24.8 mg g( 1)polymer. The affinity copolymer could be recycled by temperature-inducing precipitation and there was only about 6% loss of adsorption capacity after five recyclings. Specific activity of lipase was improved from 14IU mg(-1) to 506 IU mg(-1) protein, and its recovery achieved 82%. The affinity polymer is suitable for the purification of target proteins from the crude material with large volume and dilute solution. PMID- 20363674 TI - A review of mast cells and liver disease: What have we learned? AB - BACKGROUND: Mast cells are recognized as diverse and highly complicated cells. Aside from their notorious role in allergic inflammatory reactions, mast cells are being implicated in numerous disease processes from heart disease to cancer. Mast cells have been implicated in liver pathogenesis including hepatitis and host allograft rejection after liver transplantation. AIMS: The aim of this review is to discuss the traditional function of mast cells, their location and anatomy with regards to hepatic vasculature and the role of mast cells in hepatic diseases including liver regeneration and rejection. Finally, we will touch on the role of mast cells in liver cancer. In conclusion, we hope that the reader comes away with a better understanding of the diverse and potential role(s) that mast cells may play in liver pathologies. PMID- 20363675 TI - Three-dimensional analysis of retinal layer texture: identification of fluid filled regions in SD-OCT of the macula. AB - Optical coherence tomography (OCT) is becoming one of the most important modalities for the noninvasive assessment of retinal eye diseases. As the number of acquired OCT volumes increases, automating the OCT image analysis is becoming increasingly relevant. In this paper, a method for automated characterization of the normal macular appearance in spectral domain OCT (SD-OCT) volumes is reported together with a general approach for local retinal abnormality detection. Ten intraretinal layers are first automatically segmented and the 3-D image dataset flattened to remove motion-based artifacts. From the flattened OCT data, 23 features are extracted in each layer locally to characterize texture and thickness properties across the macula. The normal ranges of layer-specific feature variations have been derived from 13 SD-OCT volumes depicting normal retinas. Abnormalities are then detected by classifying the local differences between the normal appearance and the retinal measures in question. This approach was applied to determine footprints of fluid-filled regions--SEADs (Symptomatic Exudate-Associated Derangements)--in 78 SD-OCT volumes from 23 repeatedly imaged patients with choroidal neovascularization (CNV), intra-, and sub-retinal fluid and pigment epithelial detachment. The automated SEAD footprint detection method was validated against an independent standard obtained using an interactive 3-D SEAD segmentation approach. An area under the receiver-operating characteristic curve of 0.961 +/- 0.012 was obtained for the classification of vertical, cross layer, macular columns. A study performed on 12 pairs of OCT volumes obtained from the same eye on the same day shows that the repeatability of the automated method is comparable to that of the human experts. This work demonstrates that useful 3-D textural information can be extracted from SD-OCT scans and--together with an anatomical atlas of normal retinas--can be used for clinically important applications. PMID- 20363676 TI - Robust reconstruction of MRSI data using a sparse spectral model and high resolution MRI priors. AB - We introduce a novel algorithm to address the challenges in magnetic resonance (MR) spectroscopic imaging. In contrast to classical sequential data processing schemes, the proposed method combines the reconstruction and postprocessing steps into a unified algorithm. This integrated approach enables us to inject a range of prior information into the data processing scheme, thus constraining the reconstructions. We use high resolution, 3-D estimate of the magnetic field inhomogeneity map to generate an accurate forward model, while a high resolution estimate of the fat/water boundary is used to minimize spectral leakage artifacts. We parameterize the spectrum at each voxel as a sparse linear combination of spikes and polynomials to capture the metabolite and baseline components, respectively. The constrained model makes the problem better conditioned in regions with significant field inhomogeneity, thus enabling the recovery even in regions with high field map variations. To exploit the high resolution MR information, we formulate the problem as an anatomically constrained total variation optimization scheme on a grid with the same spacing as the magnetic resonance imaging data. We analyze the performance of the proposed scheme using phantom and human subjects. Quantitative and qualitative comparisons indicate a significant improvement in spectral quality and lower leakage artifacts. PMID- 20363677 TI - A statistical pixel intensity model for segmentation of confocal laser scanning microscopy images. AB - Confocal laser scanning microscopy (CLSM) has been widely used in the life sciences for the characterization of cell processes because it allows the recording of the distribution of fluorescence-tagged macromolecules on a section of the living cell. It is in fact the cornerstone of many molecular transport and interaction quantification techniques where the identification of regions of interest through image segmentation is usually a required step. In many situations, because of the complexity of the recorded cellular structures or because of the amounts of data involved, image segmentation either is too difficult or inefficient to be done by hand and automated segmentation procedures have to be considered. Given the nature of CLSM images, statistical segmentation methodologies appear as natural candidates. In this work we propose a model to be used for statistical unsupervised CLSM image segmentation. The model is derived from the CLSM image formation mechanics and its performance is compared to the existing alternatives. Results show that it provides a much better description of the data on classes characterized by their mean intensity, making it suitable not only for segmentation methodologies with known number of classes but also for use with schemes aiming at the estimation of the number of classes through the application of cluster selection criteria. PMID- 20363678 TI - Distributed consensus on camera pose. AB - Our work addresses pose estimation in a distributed camera framework. We examine how processing cameras can best reach a consensus about the pose of an object when they are each given a model of the object, defined by a set of point coordinates in the object frame of reference. The cameras can only see a subset of the object feature points in the midst of background clutter points, not knowing which image points match with which object points, nor which points are object points or background points. The cameras individually recover a prediction of the object's pose using their knowledge of the model, and then exchange information with their neighbors, performing consensus updates locally to obtain a single estimate consistent across all cameras, without requiring a common centralized processor. Our main contributions are: 1) we present a novel algorithm performing consensus updates in 3-D world coordinates penalized by a 3 D model, and 2) we perform a thorough comparison of our method with other current consensus methods. Our method is consistently the most accurate, and we confirm that the existing consensus method based upon calculating the Karcher mean of rotations is also reliable and fast. Experiments on simulated and real imagery are reported. PMID- 20363679 TI - Image segmentation by MAP-ML estimations. AB - Image segmentation plays an important role in computer vision and image analysis. In this paper, image segmentation is formulated as a labeling problem under a probability maximization framework. To estimate the label configuration, an iterative optimization scheme is proposed to alternately carry out the maximum a posteriori (MAP) estimation and the maximum likelihood (ML) estimation. The MAP estimation problem is modeled with Markov random fields (MRFs) and a graph cut algorithm is used to find the solution to the MAP estimation. The ML estimation is achieved by computing the means of region features in a Gaussian model. Our algorithm can automatically segment an image into regions with relevant textures or colors without the need to know the number of regions in advance. Its results match image edges very well and are consistent with human perception. Comparing to six state-of-the-art algorithms, extensive experiments have shown that our algorithm performs the best. PMID- 20363680 TI - Applications of a simple characterization of human gait in surveillance. AB - Applications of a simple spatiotemporal characterization of human gait in the surveillance domain are presented. The approach is based on decomposing a video sequence into x-t slices, which generate periodic patterns referred to as double helical signatures (DHSs). The features of DHS are given as follows: 1) they naturally encode the appearance and kinematics of human motion and reveal geometric symmetries and 2) they are effective and efficient for recovering gait parameters and detecting simple events. We present an iterative local curve embedding algorithm to extract the DHS from video sequences. Two applications are then considered. First, the DHS is used for simultaneous segmentation and labeling of body parts in cluttered scenes. Experimental results showed that the algorithm is robust to size, viewing angles, camera motion, and severe occlusion. Then, the DHS is used to classify load-carrying conditions. By examining various symmetries in DHS, activities such as carrying, holding, and walking with objects that are attached to legs are detected. Our approach possesses several advantages: a compact representation that can be computed in real time is used; furthermore, it does not depend on silhouettes or landmark tracking, which are sensitive to errors in background subtraction stage. PMID- 20363681 TI - Decentralized fuzzy Hinfinity filtering for nonlinear interconnected systems with multiple time delays. AB - In general, due to the interaction among subsystems, it is difficult to design an Hinfinity filter for nonlinear interconnected systems. This paper introduces a decentralized Hinfinity fuzzy filter design for nonlinear interconnected systems with multiple time delays via T-S fuzzy models. The T-S fuzzy model consists of N time-delay T-S fuzzy subsystems. The decentralized Hinfinity filter is designed based on this model, which the asymptotic stability and a prescribed Hinfinity performance index are guaranteed for the overall filtering error system. A sufficient condition for the existence of such a filter is established by using linear matrix inequalities that are numerically feasible. A simulation example is given to show the effectiveness of this approach. PMID- 20363682 TI - Face transformation with harmonic models by the finite-volume method with delaunay triangulation. AB - To carry out face transformation, this paper presents new numerical algorithms, which consist of two parts, namely, the harmonic models for changes of face characteristics and the splitting techniques for grayness transition. The main method in this paper is a combination of the finite-volume method (FVM) with Delaunay triangulation to solve the Laplace equations in the harmonic transformation of face images. The advantages of the FVM with Delaunay triangulation are given as follows: 1) easy to formulate the linear algebraic equations; 2) good in retaining the pertinent geometric and physical need; and 3) less central processing unit time needed. Numerical and graphical experiments have been conducted for the face transformation from a female (woman) to a male (man), and vice versa. The computed sequential errors are O(N-3/2), where N2 is the division number of a pixel into subpixels. These computed errors coincide with the analysis on the splitting-shooting method (SSM) with piecewise constant interpolation in the previous paper of Li and Bai. In computation, the average absolute errors of restored pixel grayness can be smaller than 2 out of 256 grayness levels. The FVM is as simple as the finite-difference method (FDM) and as flexible as the finite-element method (FEM). Hence, the FVM is particularly useful when dealing with large face images with a huge number of pixels in shape distortion. The numerical transformation of face images in this paper can be used not only in pattern recognition but also in resampling, image morphing, and computer animation. PMID- 20363683 TI - Active learning from stream data using optimal weight classifier ensemble. AB - In this paper, we propose a new research problem on active learning from data streams, where data volumes grow continuously, and labeling all data is considered expensive and impractical. The objective is to label a small portion of stream data from which a model is derived to predict future instances as accurately as possible. To tackle the technical challenges raised by the dynamic nature of the stream data, i.e., increasing data volumes and evolving decision concepts, we propose a classifier-ensemble-based active learning framework that selectively labels instances from data streams to build a classifier ensemble. We argue that a classifier ensemble's variance directly corresponds to its error rate, and reducing a classifier ensemble's variance is equivalent to improving its prediction accuracy. Because of this, one should label instances toward the minimization of the variance of the underlying classifier ensemble. Accordingly, we introduce a minimum-variance (MV) principle to guide the instance labeling process for data streams. In addition, we derive an optimal-weight calculation method to determine the weight values for the classifier ensemble. The MV principle and the optimal weighting module are combined to build an active learning framework for data streams. Experimental results on synthetic and real world data demonstrate the performance of the proposed work in comparison with other approaches. PMID- 20363684 TI - Individual muscle control using an exoskeleton robot for muscle function testing. AB - Healthy individuals modulate muscle activation patterns according to their intended movement and external environment. Persons with neurological disorders (e.g., stroke and spinal cord injury), however, have problems in movement control due primarily to their inability to modulate their muscle activation pattern in an appropriate manner. A functionality test at the level of individual muscles that investigates the activity of a muscle of interest on various motor tasks may enable muscle-level force grading. To date there is no extant work that focuses on the application of exoskeleton robots to induce specific muscle activation in a systematic manner. This paper proposes a new method, named "individual muscle force control" using a wearable robot (an exoskeleton robot, or a power-assisting device) to obtain a wider variety of muscle activity data than standard motor tasks, e.g., pushing a handle by hand. A computational algorithm systematically computes control commands to a wearable robot so that a desired muscle activation pattern for target muscle forces is induced. It also computes an adequate amount and direction of a force that a subject needs to exert against a handle by his/her hand. This individual muscle control method enables users (e.g., therapists) to efficiently conduct neuromuscular function tests on target muscles by arbitrarily inducing muscle activation patterns. This paper presents a basic concept, mathematical formulation, and solution of the individual muscle-force control and its implementation to a muscle control system with an exoskeleton type robot for upper extremity. Simulation and experimental results in healthy individuals justify the use of an exoskeleton robot for future muscle function testing in terms of the variety of muscle activity data. PMID- 20363685 TI - Issues of using tactile mice by individuals who are blind and visually impaired. AB - Tactile mice, computer mice modified to have tactile pin displays on their upper surface, have been developed to enable access to 2-D graphical information for individuals who are blind or visually impaired; however, they have yet to really be adopted by the community. We suggest that this is due to the significant lack of accuracy in the haptic position information, which is critical for individuals to haptically piece together a 2-D graphic. We have identified two main design issues that affect this accuracy. Making simple modifications to correct these problems, we show a significant improvement in performance. PMID- 20363686 TI - Acute adverse effects of fine particulate air pollution on ventricular repolarization. AB - BACKGROUND: The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood. OBJECTIVE: We examined the effects and time course of exposure to fine particulate matter < or = 2.5 microm in aerodynamic diameter (PM(2.5)) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania. METHODS: The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a high-resolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)-corrected QT measures: QT prolongation index (QTI), Bazett's HR-corrected QT (QTcB), and Fridericia's HR-corrected QT (QTcF). A personal PM(2.5) monitor was used to measure individual-level real-time PM(2.5) exposures for 24 hr. We averaged these data and used 30-min time-specific average PM(2.5) exposures. RESULTS: The mean age of the participants was 56 +/- 8 years, with 41% male and 74% white. The means +/- SDs for QTI, QTcB, and QTcF were 111 +/- 6.6, 438 +/- 23 msec, and 422 +/- 22 msec, respectively; and for PM(2.5), the mean +/- SD was 14 +/- 22 microg/m3. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (beta) between 30-min PM(2.5) and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM(2.5) exposure occurred within 3-4 hr. The multivariable adjusted beta (SE, p-value) due to a 10 microg/m3 increase in lag 7 PM(2.5) on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively. CONCLUSIONS: Our results suggest a significant adverse effect of PM(2.5) on ventricular repolarization. The time course of the effect is within 3-4 hr of elevated PM(2.5). PMID- 20363687 TI - Systematic review on "vitamin E and prevention of colorectal cancer". AB - Colorectal cancers (CRC) are highly prevalent cancer all over the world and need appropriate and timely prevention and treatment. Since years it has been argued that antioxidant vitamins have a potential role in the prevention of several neoplasm including colorectal cancer though the answer remained controversial. Most of the observational studies in past have shown that Vitamin E has some protective effect in the primary prevention of colorectal cancer, however its exact role is not yet established. On the other hand recently conducted experimental studies have shown variable results regarding the role of vitamin E in preventing colorectal cancers. Thus this review was conducted to study the role of vitamin E in preventing colorectal neoplasm. This review study was conducted from September 2008 to February 2009. We searched multiple electronic sources including (PUBMED) MEDLINE, Cochrane Database for identifying existing Systematic Reviews, OVID data base and other library sources to identify relevant studies for this review. Data was collected using data extraction form. Meta analysis was performed in Review Manager version 4.3. We identified four trials on vitamin E role for primary prevention of CRC, includes 94069 participants (47029 in vitamin E Vs 47040 in placebo), aged 40 years or above, who were randomized to vitamin E supplement versus placebo. The outcome measure in our review was incidence of colorectal cancer in the follow up period of 7 to 10 years. We found no sufficient evidence of vitamin E role for decreasing risk of CRC incidence (RR: 0.89, CI: 0.76, 1.05; p-value = 0.18). It has been identified in the review that Vitamin E does not have protective role in the prevention of colorectal cancer. Further studies on diverse population are required to determine the role vitamin E for the primary prevention of colorectal cancer. PMID- 20363688 TI - Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. AB - Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-alpha) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-alpha, serum total bilirubin and the activities of ALP and gamma-GTenzymes. Histopathological examination revealed that TQ administration improved LPS-induced pathological abnormalities in liver tissues. The present study conclude that TQ reduced acute endoxemia induced liver dysfunction at least in part by its anti-inflammatory, antiapoptotic and antioxidant activities. PMID- 20363689 TI - Impact of the aqueous extract of Eclipta alba on maternal aggression in rats. AB - Parturient females display impulsive behavior represented in the form of aggressive bouts when exposed to conspecifics. Prolonged aggression during the postpartum period could affect maternal care. Eclipta alba is traditionally known to induce neuropsychiatric alterations, however its ability to circumvent maternal aggression has not been elucidated. The present study was aimed to investigate the ability of the aqueous extract of Eclipta alba to suppress maternal aggression. In the single dose study, 100, 200 and 500 mg/kg body weight of the aqueous extract of Eclipta alba was administered to parturient females 30 minutes prior to maternal aggression testing against intruder males. In the multiple dose study, 100, 200 and 500 mg/kg of the extract were administered for 15 and 30 days and maternal aggression was quantified. Administration of the extract for 15 and 30 days in dose schedules of 200 and 500 mg/kg body weight significantly suppressed agonistic encounters by the dams and therefore had beneficial anti-aggressive activity. PMID- 20363690 TI - Interaction study between levofloxacin and omeprazole using urinary pharmacokinetic data. AB - The objective of this study was to observe the drug interaction between levofloxacin and omeprazole using urinary excretion data. Levofloxacin tablet and omeprazole capsule were administered separately as well as in combination in fasting condition with a wash out period of two weeks after each administration. Urine was collected at different time intervals of 0, 0-2, 2-4, 4-8, 8-12, 12-24, 24-36 and 36-48 hr post-dose and analyzed using a validated HPLC with UV detection. Different pharmacokinetic parameters for both drugs were determined using non-compartmental method. The maximum rate of excretion (R(max)) of levofloxacin was not decreased significantly when co-administered with omeprazole (p<0.05). Similarly no significant difference (p = 0.350) was observed for Rmax of omeprazole when co-administered with levofloxacin. Again the fraction of levofloxacin excreted (f(e)/f) was not changed significantly (p = 0.953) due to the co-administration of omeprazole. Similarly fraction of omeprazole excreted (f(e)/f) also remained unaffected (p = 0.672) when co-administered with levofloxacin. No significant change was observed for the area under the rate of excretion versus midpoint of time interval curve from zero to 48 hours (AURC(0 48)) for levofloxacin and omeprazole (p = 0.816 and 0.792 respectively) when administered separately and co-administered with each other. The study clearly revealed that levofloxacin and omeprazole do not undergo any kind of interactions when administered together. So it can be concluded that these two drugs can be prescribed together to achieve optimum therapeutic activity. PMID- 20363691 TI - Development of new ophthalmic suspension prednisolone acetate 1%. AB - Formulation of a new Prednisolone acetate (1%) ophthalmic suspension to obtain a better contactibility of the drug at the site of action. The formulation was evaluated and optimized based on physiological, physicochemical and pharmaceutical parameters and prepared aseptically, keeping particle size between 1-3 microm, while viscosity enhancer, preservative, chelating agent were used to increase the transient residence time, antimicrobial preservation respectively. Isotonicity of the formulation was maintained. Buffering agents used were having buffering capacity NMT 0.05%. pH adjusted at which Prednisolone acetate was stable. The finished product subjected to stress conditions to check the physical stability of the formulation. The formulation was packed in LDPE plastic vials, and subjected to accelerated stability studies at 40 degrees C and the kinetic and predictive method was employed for the determination of degradation rate constant and shelf life. The results showed that the development of a new ophthalmic formulation having significantly better contact time by the selection and optimization of viscosity (HPMC) that obtained (21 cps) with better stability studies. The results concluded that prednisolone acetate 1.0 per cent ophthalmic suspension is more effective than prednisolone phosphate 1.0 per cent ophthalmic solution in suppressing corneal inflammation. PMID- 20363692 TI - Mechanical properties and water vapour permeability of film from Haruan (Channa striatus) and fusidic acid spray for wound dressing and wound healing. AB - Aerosol is a new dosage form for wound dressing and wound healing. Concentrate of aerosols which were prepared for wound dressing and wound healing will produced films after sprayed onto the surface of wounds. The aim of this study is to evaluate the mechanical and water vapour permeability properties of the films from the aerosol concentrates. Film forming dispersions contained Haruan extract and Fusidic acid as the active ingredients, hydroxypropyl methylcellulose (HPMC) as polymer and polyethylene glycol (PEG) 400, glycerin and propylene glycol as plasticizers. Haruan extract is used to promote healing and Fusidic acid is added in formula as antibiotic to prevent the infections. The films were prepared by using casting technique. Based on the results, it is concluded that films produced from Formula E1, E2 and F4 possessed good elongation at break but low tensile strength. All Formula E, Formula F4 and F5 were permeable but Formula F5 was brittle and would peel off by themselves from the Petri dish. PMID- 20363693 TI - Subchronic toxicity studies of the ethanolic root extract of Croton zambesicus. AB - Subchronic toxicity study of the crude root extract of Croton zambesicus (27-81 mg/kg), which is used traditionally as malarial remedy, was carried out in rodents to evaluate the safety profile. Effect of the extract on body weights, haematological indices as well as liver and kidney functions and histology of various organs were investigated. Subchronic treatment of rats for 21 days caused comparable increase in body weights of rats in extract treated and control groups. The extract caused a dose-dependent increases in RBC, PCV, Hb, WBC, bleeding time and clotting time. The increases were only significant (P<0.05) at the highest dose of the extract (81 mg/kg) for RBC and WBC when compared to control. There was no significant (P>0.05) differences in the means of other haematological parameters in the extract treated groups compared to control. The extract caused significant (P<0.05-0.01) increases in the level of serum total protein, ALT, ALP, total bilirubin and total cholesterol. The was no significant (P>0.05) changes in the levels of albumin and AST. The extract did not produce any significant (P>0.05) changes in the mean concentrations of urea, creatinine, Na+, K+, and Cl- ions of rats in the extract treated groups compared to that of control. Histopathologic analysis of the vital organs revealed no significant lesions in the brain, liver, kidney, heart, spleen, ovary, and testis. The results suggest the extract to be safe when taken orally though with an insignificant effect on the liver. PMID- 20363694 TI - The intracerebroventricular (ICV) administration of W-7, a calmodulin inhibitor, attenuates the development of morphine tolerance in rats. AB - The present study was performed to determine the effect of intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. This study was carried out on male wistar rats, weighing 200-250 g. Morphine was administered daily (15 mg/kg for 8 days). The threshold to thermal nociceptive stimuli was measured by tail-flick test. W-7 (0.25, 0.5 and 1 micromol/rat) was injected through ICV. Maximal possible effect percentage (MPE %) was considered as analgesia index. Our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of W 7 (0.5 and 1 micromol/rat) decreased the development of tolerance to it. In conclusion these data showed that chronic injection of W-7 inhibited the development of morphine tolerance which indicates that calmodulin and its dependent pathways may play a role in the morphine tolerance processes. PMID- 20363695 TI - Antioxidant level in normal and dialyzed patients using FRAP method. AB - To examine the serum antioxidant levels like vit-C, vit-E and glutathione in patients with renal diseases who were subjected to dialysis and to evaluate the antioxidant by FRAP method. To find out the involvement of free radicals in pathogenesis of renal disease. Fifty patients with high levels of creatinine and urea level were included in the study of dialysis. A difference of antioxidant level of vit-C, vit-E and glutathione was observed. The study therefore suggests the importance of assessing these marker oxidative stress antioxidant capacities in renal disease during dialysis. PMID- 20363696 TI - Formulation and evaluation of mouth dissolving tablets of the Etoricoxib. AB - The demand for mouth dissolving tablets has been growing during the last decade especially for elderly and children who have swallowing difficulties. Etoricoxib is a new non-steroidal anti-inflammatory drug (NSAID) with selective cox-2 inhibitory activity, selective inhibition of cox-2 provides anti-inflammatory and analgesic activity it is commonly used for osteo-arthritis, rheumatoid arthritis, primary dysmenorrhoea, post operative dental pain and acute gout. The main criteria for mouth dissolving tablets are to disintegrate or dissolve rapidly in oral cavity with saliva in 15 sec to 60 sec with need of water. The disintegrants used should fulfill the criteria by disintegrating the tablets in specified time limit.in the present investigation variety of super disintegrants like primogel, kollidone, Ac-Di-sol, L-HPMC, L-HPC, were selected and tablets were prepared by direct compression method in different concentration like 4% and 8%. The prepared tablets were evaluated for weight variation, hardness, friability, in vitro disintegration time, wetting time, in vitro dissolution study, etc. formulation f 9 shows the lowest disintegration time (44 sec) and wetting time (52 sec). In vitro dissolution studies revealed that formulation F-9 containing 8% L-HPC showed 97% drug release at the end of 20 min. PMID- 20363697 TI - Preliminary pharmacological study of the pterocarpans macckian and trifolirhizin isolated from the roots of Ononis vaginalis. AB - Preliminary pharmacological study was conducted for the pterocarpans macckian (Mac) and trifolirhizin (Trif). The two compounds isolated from Ononis vaginalis were tested for their hepatoprotective effects against CCl4 induced hepatotoxicity in rats. Activity was accessed by measuring liver enzymes and NP SH groups. Estrogenic activity was expressed as increase in uterine weight of young female rats. Rat paw edema as a model of acute inflammation induced in Wistar rats using carragenan was used to evaluate the anti-inflammatory activity. Percentage inhibition of the aggregation induced by adenosine diphosphate (ADP) to platelets-rich plasma (PRP) obtained from rats was used as measure for antiplatelet aggregation effect. The aglycone Mac was only more active than the glycoside Trif in the anti-inflammatory assay. It resulted in 65.7% reduction in carregeenan induced rat paw edema compares with 79.8% reduction by indomethacin at the same molar concentration. The activity of Trif was about half of that of silymarin in reducing the elevated levels of liver enzymes at the same molar concentration. About 10 fold molar concentration of Trif produced about half fold increase in uterine weight produced by 17beta-estradiol. PMID- 20363698 TI - Effect of lithium metal on the chemical status of glutathione (GSH) present in whole blood (especially in plasma and cytosolic fraction in human blood). AB - Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Thus the effect of Lithium was interesting to study on the glutathione (GSH) level in vivo conditions. Ellman's method has been used to see the effect of lithium on glutathione (GSH) level in whole blood. The time dependent effect of Lithium on the chemical status of glutathione (GSH) was determined in the whole blood (Plasma and cytosolic fraction) of human. The concentration of Glutathione was drastically decreased. The decrease in the glutathione level was concentration and time of interaction dependent, probably due to oxidation of glutathione (GSH) to corresponding disulphide (GSSG). In this paper the effect of Lithium on the Thiol/GSH level was discussed in vitro, which in principal may present a model of in vivo reaction. PMID- 20363699 TI - Erythrocytes as carrier for prednisolone: in vitro and in vivo evaluation. AB - Resealed erythrocytes, as drug delivery system has tremendous potential to achieve site specificity and prolonged release of drug thereby enhancing therapeutic index and patient compliance. In the present investigation erythrocytes obtained from healthy volunteers were loaded with prednisolone using preswell dilution and dilution technique with two different cross-linking agents, glutaraldehyde and dimethylsulphoxide. Carrier erythrocytes, having acceptable loading parameters showed increased percentage drug content with the addition of cross-linking agents. In vitro drug release followed zero-order kinetics, haemoglobin content was found to be satisfactory and osmotic fragility study indicated that increased drug entrapment efficiency was found at 0.3%w/v concentration of sodium chloride (hypotonic solution). In vivo tissue distribution studies were carried out for optimized formulation and order of distribution was found to be Liver>Lung>Kidney> Spleen. The developed drug delivery system is endowed with several exclusive advantages and hence holds potential for further research and clinical application. PMID- 20363700 TI - Buspirone attenuates tolerance to analgesic effect of morphine in mice with skin cancer. AB - Adjuvant drugs that can delay tolerance to morphine analgesia may lead to improved management of pain in chronic disease such as cancer. This study was aimed to investigate effect of buspirone, as a partial agonist of 5-HT1A receptor, on tolerance induced to morphine analgesic effect in animals with skin cancer. Study was carried on female Swiss albino mice. For skin tumorigensis, mice were treated with single dose of 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by multiple dose of croton oil. Tolerance to morphine analgesia was induced by daily subcutaneous (sc) injection of morphine (5mg/kg for 30 days) and assayed by using the hot plate method. Results obtained from this study showed that pain threshold in mice with skin cancer were significantly lower. Tolerance to analgesic effect of morphine (5 mg/kg, sc) was appeared at day 15, whereas, in normal and skin tumor bearing mice co-treated daily with morphine (5 mg/kg, sc) and three different intraperitoneal (ip) doses of buspirone (5, 7.5 and 10 mg/kg) tolerance was observed at days 25 and 30. In conclusion our data indicate that concurrent use of morphine with buspirone may produce good cancer pain control and attenuate development of tolerance. PMID- 20363701 TI - Oxytocic effects of the aqueous leaf extract of Costus lucanusianus - family Costaceae on isolated non-pregnant rat uterus. AB - Costus lucanusianus J. Braun (Costaceae) is a climbing herb, found mainly in the Niger Delta region of Nigeria. This plant is locally used in situations of pains, inflammation, dysmenorrhoea and in pyrexia. The purpose of this study was to investigate this claim with view to validating scientifically the ethno-medicinal usage. The aqueous extract was subjected to pharmacological testing in vitro on a piece of isolated rat uterus previously pretreated with 1 mg/kg stilbestrol for 24 h. The dose response curves of oxytocin and that of the extract were first obtained. The effects of antagonists like atropine (1 mg) and salbutamol (2 microg) on the dose response curve of the extract were also investigated. Possible synergy was investigated via co-administration of the extract and oxytocin. Finally the proximate analysis of the extract was investigated. The aqueous extract of C. lucanusianus and oxytocin both produced a dose dependent contraction of the uterus. An effect of 0.63+/-0.06 g force of uterine contraction produced by 12.5 mg of the extract was increased to 1.37+/-0.09 g when 200 mg of the extract was administered. Oxytocin at 0.16 i.u was observed to produce a similar force of contraction with 200 mg of the aqueous extract. Synergy was established as co administration of the extract at 200 mg and oxytocin at 0.08 i.u, produced higher contractile effect, significantly higher (p<0.05) than when either the extract (200mg) or oxytocin (0.08 i.u) was administered alone. Both atropine and salbutamol significantly (p<0.0001) inhibited the contractile effect produced by the extract. The inhibitory effect showed by atropine on the contractile effect of the extract seems to suggest the involvement of muscarinic receptors. The proximate analysis carried out in this study is used to establish the identity of the crude drug sample. A moisture content of 10.047 % was obtained. The total ash is a measure of the non-volatile inorganic constituents remaining after ashing. The values of 3.42 % were obtained. PMID- 20363702 TI - Hypoglycemic and hypolipidemic effects of an aqueous extract of Chamaerops humilis leaves in obese, hyperglycemic and hyperlipidemic Meriones shawi rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: An aqueous concoction made from the leaves of Chamaerops humilis (L.) (dwarf fan palm), is used in the Moroccan traditional medicine for the treatment of diabetes, as well as a number of other diseases. The aim of the study was to experimentally validate the use of C. humilis in the folk treatment of diabetes as well as to determine if the aqueous leaf extract of this plant has hypolipidemic properties in an animal model of obesity, hyperglycemia and hyperlipidemia. The animal model consisted of experimentally induced obesity, hyperglycemia and hyperlidemia (OHH) in Meriones shawi rats. In the acute study, OHH M. shawi rats (n = 8) were given a single oral dose (10 mg/kg) of an aqueous extract of C. Humilis leaves (plant-extract); taurine (8 mg/kg) was used as the positive control. Plasma glucose levels were determined at 2-, 4- and 6-hr after the dose. In the sub-chronic study, groups of OHH rats (n = 8 for each group) were given daily oral doses of the plant-extract and taurine (at the above doses) for 30 days. Body weight (BW), plasma glucose, total cholesterol and triglycerides were measured at 15 and 30 days of dosing. The M. shawi rats developed OHH when maintained on a hypercaloric diet and forced physical inactivity for 90 days. A single oral dose of the plant-extract decreased plasma glucose levels with the maximum effect occurring at 4-hr after the dose (6.88 +/- 1.38 mmol/L compared to baseline 12.04 +/- 0.94 mmol/L; P<0.01). Taurine also decreased plasma glucose (from 12.26 +/- 1.27 mmol/L to 9.15 +/- 1.27 mmol/L; P<0.05); water treated control group did not show any effect. In normal M. shawi (normal) rats, none of the treatments had significant effect on glucose levels. In the sub-chronic study, daily oral administration of the plant-extract or taurine for 30 days to the OHH rats resulted in a significant decrease in BW (from 241 +/- 8 g to 165 +/- 11 g; P<0.001 for the extract, and from 221 +/- 13 g to 189 +/- 11 g; P<0.05 for taurine); water treated control rats showed no effect. In normal rats, administration of the plant-extract or taurine for 30 days resulted in an insignificant decrease in BW, while water administration caused a small (normal) increase in the weight. Plasma glucose levels of the OHH rats decreased significantly with daily dosing with the plant-extract [from baseline 12.04 +/- 0.94 mmol/L to 6.10 +/- 0.27 mmol/L (P<0.05) after 15 days, and to 4.84 +/- 0.22 mmol/L (P<0.001) after 30 days]. Taurine was less effective (P<0.05), while water treated control group did not show any effect. In the normal rats, administration of the plant-extract or taurine for 30 days resulted in a small decrease in glycemia. Administration of plant-extract caused a significant decrease in plasma levels of total cholesterol [from baseline of 3.46 +/- 0.21 mmol/L to 1.05 +/- 0.06 mmol/L (p<0.01) after 15 days and to 0.62 +/- 0.02 mmol/L (p<0.001)] after 30 days, and triglycerides [from baseline of 1.15 +/- 0.17 mmol/L to 0.47 +/- 0.04 mmol/L (p<0.001) after 15 days and to 0.37 +/- 0.03 mmol/L (p<0.001) after 30 days]. Taurine was less effective, while water treated control group did not show any effect. There was no effect of these treatments on lipid levels in normal rats. The results of this study validate the traditional use of the leaves of C. humilis in the treatment of diabetes in Morocco. Since, the aqueous leaf extract also decreased total cholesterol and triglycerides, the plant may also be useful in the management of secondary complications of diabetes (dyslipidemia). Furthermore, the plant may become a good source of antidiabetic medication. PMID- 20363703 TI - Synthesis of some novel analogues of 4-(1-Pyrrolidinyl) Piperidine and their effect on plasma glucose level. AB - In the present study some compounds of 4-(1-Pyrrolidinyl) Piperidine (I) have been synthesized. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques. All the derivatives (II, III, IV and V) and the parent compound (I) at the dose of 100 mg/kg were evaluated for their effect on plasma glucose level. Compound (II) was the only derivative which showed effect on plasma glucose level. PMID- 20363704 TI - Antimicrobial effects of Boesenbergia pandurata and Piper sarmentosum leaf extracts on planktonic cells and biofilm of oral pathogens. AB - Increasing awareness of hazards associated with the use of antibiotic and chemical agents has accelerated investigations into plants and their extracts as new sources of antimicrobial agents. Therefore, this study aimed at determining the effects of oil and 95% ethanol extracts of Boesenbergia pandurata rhizomes and Piper sarmentosum leaf against four oral pathogens which were Streptococcus mutans, Lactobacillus sp., Aggregatibacter actinomycetemcomitans and Candida albicans. Employing the disc diffusion and broth microdilution methods, the results showed that B. pandurata oil (BPO) was the most effective extract against C. albicans. Time-kill assay with the BPO demonstrated killing of C. albicans at concentrations equal to 2 and 2.5 times the MIC. The times required to reach the fungicidal endpoint at 2 and 2.5 times the MIC were 60 and 44 min, respectively. In addition, our results also demonstrated that the BPO possesses potent anti Candida biofilm activity in vitro. Therefore, the BPO could be considered as a natural antifungal agent against Candida infections and has significant potential for further investigation. PMID- 20363705 TI - Formulation and evaluation of Cetirizine dihydrochloride orodispersible tablet. AB - Cetirizine orodispersible tablets were prepared to achieve quick onset of action and for maximum bioavailability. Tablets were prepared using cetirizine along with camphor and mannitol in the proportion of 1:1:1, 1:1:3, and 1:1:6. The flow property of granules was found to be good for the formulation CZ2 (1:1:3). The hardness and friability of all the formulations were found to be within the standard limit for orodispersible tablets. Disintegration time was found to be rapid in formulation CZ2 (1:1:3).The in vitro dissolution time was found to be 100% in 11 minutes for the formulation CZ2 (1:1:3). PMID- 20363706 TI - Evaluation of antiglycosidase and anticholinesterase activities of Boehmeria nivea. AB - In this era, major community worldwide is suffering from diabetes type II, cancer and neurodegenerative disorders. To overcome these diseases, in the screening of Korean medicinal plants, we studied the whole plant of Boehmeria nivea (B. nivea). The methanolic leaf, stem and root extracts of B. nivea and their respective n-hexane, methylene chloride (CH(2)Cl(2)), ethyl acetate (EtOAc), n butanol (BuOH) and aqueous fractions were investigated for their total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, alpha-glucosidase, beta-glucosidase, alpha-galactosidase, beta galactosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Profound TPC and DPPH free radical scavenging activities were observed in the EtOAc and BuOH fractions of root, where the BuOH fraction showed high-pitched alpha-glucosidase inhibition and the EtOAc layer showed the maximum beta-glucosidase inhibition. Furthermore, the leaf extract demonstrated the highest beta-galactosidase inhibitory activity, but no alpha galactosidase inhibition was seen in any of the plant parts. Notable BChE and moderate AChE inhibitory activity was found in whole plant. It can be suggested that whole plant of B. nivea provides a strong biochemical rationale as one of the good choices for the treatment of diabetes type II, cancer and neurodegenerative diseases (AD, etc). PMID- 20363708 TI - Mitochondrial disease: when the powerhouse goes awry. AB - Knowledge of and interest in mitochondrial disease is relatively recent. The first diagnosis of a mitochondrial cytopathy occurred in 1962. Since then, researchers have elucidated hundreds of types of mutant mitochondrial DNA and mapped their repercussions. This article walks the reader through the basics of mitochondrial function--normal and mutant. Mitochondrial cytopathies appear first in organs with high-energy needs; once a threshold of mutant mitochondrial DNA is exceeded, manifestations can be single or multisystem conditions. Although these conditions are currently incurable, some therapies aimed at enhancing mitochondrial function or scavenging free radicals may help individual patients. Certain nonpharmacological therapies should be employed in all patients. Research findings suggest that mitochondrial functioning may have a greater role in other pathologies than previously assumed. PMID- 20363709 TI - Effective communication with prescribers: tips and insights from both sides of the fence. AB - Although effective collaboration between pharmacists and prescribers is critically important, their relations are often strained. Lack of or inadequate communication of the medication-related problem can hinder pharmacists from receiving timely responses to their recommendations and affect the quality of care provided to the patient. Here, seasoned consultant pharmacists and medical directors suggest simple strategies to help cultivate more collaborative, effective, and satisfying relationships. PMID- 20363710 TI - Simulating age-related changes in color vision to assess the ability of older adults to take medication. AB - OBJECTIVE: To determine if simulated, age-related changes in color vision can adversely affect one's ability to properly take medication as simulated by bead selection. DESIGN: Randomized controlled study. SETTING: University site. PARTICIPANTS: University students 18 to 26 years of age without eye disorders that would affect color vision. INTERVENTIONS: Yellow-lens glasses to represent age-related color vision changes. MAIN OUTCOME MEASURES: The number of correct beads selected and rating of task difficulty. The secondary outcomes were participants' responses based on which colors and color pairs were most difficult to discern and strategies they might have used to select beads. RESULTS: The control group had no difficulties in selecting the appropriate beads, while the experimental group had significantly more mistakes, particularly with colors in the blue-violet spectrum. Average scores for the total number correct for the control and experimental groups were 36 (100%) and 27 (74.4%), P < 0.001, respectively, out of a possible 36 correct. CONCLUSION: Declines in color vision with age can adversely affect an individual's abilities to appropriately select medications. For patients taking several medications, declines in color vision should be considered when counseling older persons on strategies for compliance. Although more studies are still needed to further generalize these findings to the geriatric population, this study has shown color vision can adversely affect medication compliance. PMID- 20363711 TI - Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. AB - An 84-year-old patient diagnosed with a vitamin D deficiency was given a prescription for ergocalciferol (vitamin D2) 50,000 units weekly. The prescription was incorrectly filled for ergocalciferol 50,000 units daily. Incorrect therapy continued for two months. The patient's vitamin D level increased from < 7.0 ng/mL to 100 ng/mL over a six-month span. The patient complained of decreased appetite and significant weight loss and presented with an elevated International Normalized Ratio at a pharmacist-run anticoagulation clinic. In conjunction with the physician, the pharmacist discontinued vitamin D therapy and monitored levels.Vitamin D plays an integral role in the body's ability to absorb calcium and regulate calcium homeostasis. Further benefits have been reported regarding the role of vitamin D in muscle strength, cardiovascular health, and in preventing osteoporosis and falls. Vitamin D deficiency is widespread in the older adult population as a result of low dietary intake, decreased sun exposure, decreased intrinsic vitamin D production, and decreased vitamin D receptor activity. Replenishment using high-dose ergocalciferol is one common replenishment therapy. Patients also are able to supplement with nonprescription vitamin D products of varying strengths. While many older patients can be expected to have vitamin D deficiencies, pharmacists should be aware of appropriate replenishment therapies and correct dosing of different vitamin D products. Pharmacists also should be familiar with possible toxic effects of vitamin D, particularly as public awareness of benefits continues to increase. PMID- 20363712 TI - Communicationg with residents and families. PMID- 20363713 TI - ASCP Reports. PMID- 20363714 TI - Leg asymmetries and coordination dynamics in walking. AB - Models of interlimb coordination (H. Haken, J. A. S. Kelso, & H. Bunz, 1985; P. N. Kugler & M. T. Turvey, 1987) were tested in walking by examining the role of asymmetries between limbs. Participants walked on a treadmill with and without a metronome. Five asymmetry conditions were created via ankle loads of 0, 3, or 6 kg on either leg. With the metronome, participants matched the target period. Without the metronome, stride rate slowed as the mass was increased on either leg. The loads led to an increase in stride period that was predicted by Huygens' law and the hybrid pendulum-spring model. In agreement with extended Haken-Kelso Bunz model predictions, leg asymmetries led to deviations from antiphase coordination. Also, perception-action coordination was influenced by the asymmetry between the legs and metronome. In contrast, no predicted stability effects were observed. These findings reveal that some properties of interlimb coordination, apparent in laboratory-based tasks, can also be observed in human walking. PMID- 20363715 TI - Neuroprotective effects of testosterone on regenerating spinal cord motoneurons in rats. AB - Degeneration in the CNS and peripheral nervous system consists of degradation and phagocytosis of axons and their myelin sheath distal to the site of injury. Testosterone is a gonadal sex steroid hormone that plays an important role in CNS development. One of the lesser-known testosterone actions is neuroprotection. In the present study, the authors investigated the neuroprotectective effect of intracerebral ventricular injection of testosterone on the number of spinal motoneurons after sciatic nerve crush. In all, 32 male Wistar rats were divided to 4 groups (control, compression, compression + castration, compression + testosterone injections; n = 8). Four weeks after compression the lumber segments of spinal cord were sampled, processed, sectioned serially, and stained with toluidine blue (pH = 4.65) by using steriological quantitative technique (physical dissector), the number of alpha motoneurons in the right ventral horns of spinal cord were counted and compared between groups. Statistical analyses showed that testosterone injections (1 microl icv, 4 times, 1 week interval between injections) significantly (p < .05) reduced neuronal damage. These results indicated that testosterone has an obvious neuroprotective effect on lumbar spinal motoneurons. PMID- 20363716 TI - Environmental factors and nosology of the endocrine system. PMID- 20363717 TI - Definition, classification and mechanism of action of endocrine disrupting chemicals. PMID- 20363719 TI - Environmental chemicals targeting thyroid. AB - Thyroid hormones (THs) are required for normal brain and somatic development and for the proper regulation of physiology in both children and adults. Thyroid function is controlled by the dynamic interrelationships between the hypothalamus, the pituitary and the thyroid. These dynamic relationships maintain circulating levels of THs within a narrow range under normal conditions. Normally, there is likely to be a tight relationship between changes in circulating levels of THs and changes in TH action in various target tissues. This relationship is maintained by tissue-level mechanisms that include TH metabolism and transport. Environmental chemicals that interfere with TH signaling mechanisms (Endocrine Disrupting Chemicals, EDCs) may produce adverse effects both in the individual and in a population. Because of the complex nature of the regulation of thyroid function and TH action, the consequences of EDC exposure is also likely to be complex and our ability to understand these effects as well as to screen for potential EDCs must consider this complexity. Specifically, if there are chemicals in the environment that directly interfere with TH action through their receptors but do not affect circulating TH levels, they would not be identified as thyroid toxicants by currently applied screening methods or by epidemiological studies. The goal of this review is therefore to identify the issues that must be clearly resolved before effective risk assessment can be performed. PMID- 20363718 TI - Neuroendocrine targets of endocrine disruptors. AB - The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions. PMID- 20363720 TI - Epigenetics, brain, behavior, and the environment. AB - Early experiences can modify regulatory factors affecting gene expression in such a way that, although the DNA sequence itself is not changed, the individual's physiology and behavior is substantially influenced. In some instances these epigenetic effects are exerted upon exposure, while in other instances they are transmitted across generations via incorporation into the germline. Examples of both types of epigenetic effects are presented. First, experience with siblings (littermates) organizes behaviors and their underlying neural substrates in such a way that, as adults, rats and knockout mice behave differently. Second, exposure to the fungicide vinclozolin early in pregnancy imprints the male lineage in such a manner that rats exhibit distinct behavioral profiles as well as unique patterns of gene expression in relevant brain regions. Taken together, this work demonstrates that present and past environments alike modify both social and affiliative related behaviors and their related metabolic activity in specific brain nuclei as well as influencing the abundance of specific genes altering the epigenome in the target brain areas. PMID- 20363721 TI - Clinical implications of molecular studies for the diagnosis of thyroid cancer. PMID- 20363722 TI - TSH suppressive therapy: an overview of long-term clinical consequences. AB - An overview of long-term clinical consequences of TSH suppressive therapy provides evidence that serum TSH levels should be maintained at levels <0.1 mU/l in high-risk (stage III and IV) patients, whereas lower-risk patients should be allowed to have their TSH levels rise into the normal range after residual disease has been ruled out by imaging and/or stimulated thyroglobulin measurement. The proper management of patients with known residual thyroid cancer, who are also elderly or who have underlying serious comorbidities (e.g., osteoporosis, cardiovascular disease, diabetes), is uncertain and requires a high degree of clinical experience and judgment. PMID- 20363723 TI - The role of iodine and delta-iodolactone in growth and apoptosis of malignant thyroid epithelial cells and breast cancer cells. AB - OBJECTIVE: As we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy eicosatrienoic acid (delta-iodolactone). In this communication we compare the effect of iodide, molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines (B-CPAP cells, FTC-133 cells and 8505C cells) as well as on human breast cancer cells (MCF 7). METHODS: Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and MCF 7 cells in Rowswell Park Memorial Institute (RPMI) culture medium, both containing 10% (v/v) Fetal Calf Serum (FCS), until they were confluent. Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM (thyroid cancer cells) or in RPMI medium (MCF 7 cells) both containing 5% FCS. Thereafter, different concentrations of iodide, iodine or delta-iodolactone were added for 24 h. Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells. Apoptosis was determined by a mitochondrial potential assay. RESULTS: The growth rate of B-CPAP cells was unaffected by iodide, but was reduced by high concentreations of molecular iodine (100 and 500 microM). However, delta-iodolactone significantly reduced cell proliferation already with low concentrations (5 microM and 10 microM) and further in a dose-dependent manner up to 82%. FTC-133 and 8505C cells were unaffected by iodide, iodine or delta-iodolactone. In contrast, in MCF 7 cells, molecular iodine (100 microM) inhibited growth from 100% to 83% but delta iodolactone (1, 5 and 10 microM) dose-dependently decreased growth rate from 100% to 82% and 62%, respectively. The inhibition of growth was through apoptosis, and not necrosis, as the amount of apoptotic cells corresponded to the growth inhibition. CONCLUSION: delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells. PMID- 20363724 TI - The differential impact of volatile and intravenous anaesthetics on stress response in the swine. AB - OBJECTIVE: To compare the effects of various anaesthetics on stress response in the presence and absence of surgical stimulation. DESIGN: Twenty-nine pigs scheduled to undergo surgical central vein catheter placement were randomly allocated to receive only sedation with ketamine-midazolam (group SHAM, n=5) or general anaesthesia with either propofol 8 mg/kg/h (group PROP, n=8), sevoflurane 1.0 MAC (group SEVO, n=8) or desflurane 1.0 MAC (group DESF, n=8). Following surgery, anaesthesia was maintained for a total period of 4 hours. Thyroid hormones, noradrenaline, cortisol, corticotrophin (ACTH), beta-endorphin, interleukin-1beta and -6 and tumor necrosis factor-alpha were determined by appropriate methodology after premedication (t0), after surgical procedure (t1) and at the end of 4h (t2). RESULTS: At t1 ACTH and beta-endorphin increased in all groups, thyroxin in groups SEVO, DESF and PROP, noradrenaline in group SEVO and cortisol in the SHAM and PROP groups. At t2 cortisol and ACTH levels were lower in the PROP compared to SEVO group. Serum cytokines were not significantly altered in either group. CONCLUSIONS: The choice of the general anaesthetic did not affect thyroid hormones levels in either the presence or absence of surgical stimulus. In the presence of surgical stimulation, sevoflurane resulted in higher noradrenaline levels and in higher activity of the ACTH-cortisol axis compared to propofol. PMID- 20363725 TI - The role of T-lymphocyte subsets and interleukin-5 blood levels among Indian subjects with autoimmune thyroid disease. AB - OBJECTIVE: Autoimmune Thyroid Disease (AITD) results from an interaction of exogenous and endogenous factors in a genetically predisposed individual. AITD is being increasingly reported among the Indian population. Lymphocyte subsets and levels of interleukin-5 (IL- 5) were studied in the peripheral blood of patients with AITD. DESIGN: Subjects diagnosed with either hyperthyroidism due to Graves' Disease (GD) or with primary hypothyroidism due to Hashimoto's Thyroiditis (HT) were consecutively recruited. Euthyroid controls were also recruited for comparison. Lymphocyte subsets (CD4 and CD8 counts, CD4/CD8 ratio) were evaluated by flow cytometry and IL-5 levels were determined by the sandwich ELISA method. RESULTS: Nineteen subjects with GD, 16 subjects with HT and 10 controls were studied. CD4/CD8 ratios were found to be significantly lower only in subjects with HT compared to controls. Serum IL-5 values were significantly higher in both GD and HT in comparison to controls. CONCLUSIONS: The study found increased levels of IL-5 and reduction in ratios of CD4/CD8 lymphocytes in the peripheral blood of patients with HT, but only IL-5 was increased in GD. High levels of IL-5 could have resulted in the high titres of antithyroid antibodies and may therefore be considered to play a more significant role than peripheral lymphocytes in the pathogenesis of AITD in the Indian population. PMID- 20363726 TI - Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin secreting pituitary adenoma. AB - Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP. PMID- 20363727 TI - Metastatic bronchial neuroendocrine tumor to the pineal gland: a unique manifestation of a rare disease. AB - Metastatic Neuroendocrine Tumor (NET) to the pineal gland is a unique manifestation previously unreported in the literature. We describe an unusual case of metastatic bronchial NET to the pineal gland in a 71-year-old male patient. His primary NET had been resected six years previously and there was no indication of the presence of disseminated metastatic disease at that time. Due to increased uptake by the pituitary gland on the post-operative 111Indium pentetreotide scintigraphy (Octreoscan), an intra-sellar mass was diagnosed and excised using a transsphenoidal approach; histology revealed an unrelated non functional pituitary macroadenoma. Four years later, a new mass appeared on MRI, involving the pineal gland, and was diagnosed on biopsy as a metastatic lesion from the original bronchial NET. Since this lesion was not accessible to surgery, it was treated successfully with radiosurgery. The case suggests that NETs should be considered in the differential diagnosis of pineal gland metastases and that radiosurgery may be an effective alternative in the treatment of these patients. PMID- 20363728 TI - Supervised normalization of microarrays. AB - MOTIVATION: A major challenge in utilizing microarray technologies to measure nucleic acid abundances is 'normalization', the goal of which is to separate biologically meaningful signal from other confounding sources of signal, often due to unavoidable technical factors. It is intuitively clear that true biological signal and confounding factors need to be simultaneously considered when performing normalization. However, the most popular normalization approaches do not utilize what is known about the study, both in terms of the biological variables of interest and the known technical factors in the study, such as batch or array processing date. RESULTS: We show here that failing to include all study specific biological and technical variables when performing normalization leads to biased downstream analyses. We propose a general normalization framework that fits a study-specific model employing every known variable that is relevant to the expression study. The proposed method is generally applicable to the full range of existing probe designs, as well as to both single-channel and dual channel arrays. We show through real and simulated examples that the method has favorable operating characteristics in comparison to some of the most highly used normalization methods. AVAILABILITY: An R package called snm implementing the methodology will be made available from Bioconductor (http://bioconductor.org). CONTACT: jstorey@princeton.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20363730 TI - ACCUSA--accurate SNP calling on draft genomes. AB - SUMMARY: Next generation sequencing technologies facilitate genome-wide analysis of several biological processes. We are interested in whole-genome genotyping. To our knowledge, none of the existing single nucleotide polymorphism (SNP) callers consider the quality of the reference genome, which is not necessary for high quality assemblies of well-studied model organisms. However, most genome projects will remain in draft status with little to no genome assembly improvement due to time and financial constraints. Here, we present a simple yet elegant solution ('ACCUSA') that considers both the read qualities as well as the reference genome's quality using a Bayesian framework. We demonstrate that ACCUSA is as good as the current SNP calling software in detecting true SNPs. More importantly, ACCUSA does not call spurious SNPs, which originate from a poor reference sequence. AVAILABILITY: ACCUSA is available free of charge to academic users and may be obtained from ftp://bbc.mdc-berlin.de/software. ACCUSA is programmed in JAVA 6 and runs on any platform with JAVA support. CONTACT: christoph.dieterich@mdc-berlin.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20363729 TI - An integer programming formulation to identify the sparse network architecture governing differentiation of embryonic stem cells. AB - MOTIVATION: Primary purpose of modeling gene regulatory networks for developmental process is to reveal pathways governing the cellular differentiation to specific phenotypes. Knowledge of differentiation network will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of cellular environment. RESULTS: We have developed a novel integer programming-based approach to reconstruct the underlying regulatory architecture of differentiating embryonic stem cells from discrete temporal gene expression data. The network reconstruction problem is formulated using inherent features of biological networks: (i) that of cascade architecture which enables treatment of the entire complex network as a set of interconnected modules and (ii) that of sparsity of interconnection between the transcription factors. The developed framework is applied to the system of embryonic stem cells differentiating towards pancreatic lineage. Experimentally determined expression profile dynamics of relevant transcription factors serve as the input to the network identification algorithm. The developed formulation accurately captures many of the known regulatory modes involved in pancreatic differentiation. The predictive capacity of the model is tested by simulating an in silico potential pathway of subsequent differentiation. The predicted pathway is experimentally verified by concurrent differentiation experiments. Experimental results agree well with model predictions, thereby illustrating the predictive accuracy of the proposed algorithm. CONTACT: ipb1@pitt.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20363731 TI - Studying the co-evolution of protein families with the Mirrortree web server. AB - SUMMARY: The Mirrortree server allows to graphically and interactively study the co-evolution of two protein families, and investigate their possible interactions and functional relationships in a taxonomic context. The server includes the possibility of starting from single sequences and hence it can be used by non expert users. AVAILABILITY AND IMPLEMENTATION: The web server is freely available at http://csbg.cnb.csic.es/mtserver. It was tested in the main web browsers. Adobe Flash Player is required at the client side to perform the interactive assessment of co-evolution. CONTACT: pazos@cnb.csic.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20363732 TI - Streamlining the construction of large-scale dynamic models using generic kinetic equations. AB - MOTIVATION: Studying biological systems, not just at an individual component level but at a system-wide level, gives us great potential to understand fundamental functions and essential biological properties. Despite considerable advances in the topological analysis of metabolic networks, inadequate knowledge of the enzyme kinetic rate laws and their associated parameter values still hampers large-scale kinetic modelling. Furthermore, the integration of gene expression and protein levels into kinetic models is not straightforward. RESULTS: The focus of our research is on streamlining the construction of large scale kinetic models. A novel software tool was developed, which enables the generation of generic rate equations for all reactions in a model. It encompasses an algorithm for estimating the concentration of proteins for a reaction to reach a particular steady state when kinetic parameters are unknown, and two robust methods for parameter estimation. It also allows for the seamless integration of gene expression or protein levels into a reaction and can generate equations for both transcription and translation. We applied this methodology to model the yeast glycolysis pathway; our results show that the behaviour of the system can be accurately described using generic kinetic equations. AVAILABILITY AND IMPLEMENTATION: The software tool, together with its source code in Java, is available from our project web site at http://www.bioinf.manchester.ac.uk/schwartz/grape CONTACT: jean marc.schwartz@manchester.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20363733 TI - Relationship between subjective test feedback provided by high-school athletes during computer-based assessment of baseline cognitive functioning and self reported symptoms. AB - Subjective feedback about distractions or problems encountered during computerized assessment was provided by 538 out of a pool of 1659 high-school athletes who completed baseline testing using ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing). Three types of feedback were included: (a) environmental, (b) computer-based (mechanical), and (c) instruction-based (associated with difficulty understanding test instructions). One-way analyses of variance were conducted and revealed relationships between greater symptom reporting and any type of feedback, environmental feedback, and instruction-based feedback. Increased symptom reporting was noted for female students. Additional relationships were noted between providing computer-based feedback and faster reaction time; and between history of concussion and providing instruction-based feedback. Athletes endorsing more symptoms at baseline scored significantly worse on ImPACT, as reflected in decreased visual memory performance. Results suggest that feedback provided during computerized assessment may yield information about symptom reporting and test-taking style, which may also be of particular interpretive utility when athletes minimize their symptoms. PMID- 20363734 TI - Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival. AB - Retinal pigment epithelial (RPE) cell integrity is critical for the survival of photoreceptor cells. Bcl-x(L) is a major anti-apoptotic Bcl-2 protein required for RPE cell survival, and phosphorylation of Bcl-x(L) at residue Ser-62 renders this protein pro-apoptotic. In this study, we identify serine/threonine protein phosphatase 2A (PP2A) as a key regulator of Bcl-x(L) phosphorylation at residue Ser-62 in ARPE-19 cells, a spontaneously arising RPE cell line in which Bcl-x(L) is highly expressed. We found that either PP2A inhibitor okadaic acid or depletion of catalytic subunit alpha of PP2A (PP2A/Calpha) by small interfering RNA enhanced Bcl-x(L) phosphorylation when activated with hydrogen peroxide and tumor necrosis factor alpha-induced oxidative stress. Disruption of PP2A/Calpha exacerbated oxidative stress-induced apoptosis. PP2A/Calpha colocalized and interacted with S62Bcl-x(L) in cells stressed with H(2)O(2)/tumor necrosis factor alpha. By contrast, the omega-3 fatty acid docosahexaenoic acid derivative, neuroprotectin D1 (NPD1), a potent activator of survival signaling, down regulated oxidative stress-induced phosphorylation of Bcl-x(L) by increasing protein phosphatase activity. NPD1 also attenuated the oxidative stress-induced apoptosis by knockdown of PP2A/Calpha and increased the association of PP2A/Calpha with S62Bcl-x(L) as well as total Bcl-x(L). NPD1 also enhanced the heterodimerization of Bcl-x(L) with its counterpart, pro-apoptotic protein Bax. Thus, NPD1 modulates the activation of this Bcl-2 family protein by dephosphorylating in a PP2A-dependent manner, suggesting a coordinated, NPD1 mediated regulation of cell survival in response to oxidative stress. PMID- 20363735 TI - Activation of JAK2-V617F by components of heterodimeric cytokine receptors. AB - The JAK2-V617F mutation is an important etiologic factor for the development of myeloproliferative neoplasms. The mechanism by which this mutated tyrosine kinase initiates deregulated signals in cells is not completely understood. It is believed that JAK2-V617F requires interactions with homodimeric cytokine receptors to elicit its transforming signal. In this study, we demonstrate that components of heterodimeric cytokine receptors can also activate JAK2-V617F. Expression of IL27Ra, a heterodimeric receptor component, enhanced the activation of JAK2-V617F and subsequent downstream signaling to activation of STAT5 and ERK. In addition, expression of components of the interleukin-3 receptor, IL3Ra and the common beta chain, activated JAK2-V617F as well as STAT5 and ERK. Importantly, expression of IL27Ra functionally replaced the requirement of a homodimeric cytokine receptor to promote the activation and transforming activity of JAK2-V617F in BaF3 cells. Tyrosine phosphorylation of IL27Ra was not required to induce activation of JAK2-V617F or STAT5, or to enhance the transforming activity of JAK2-V617F. Expression of IL3Ra or the common beta chain in BaF3 cells also enhanced the ability of JAK2-V617F to transform these hematopoietic cells. However, the heterodimeric receptor component IL12RB1 did not enhance the activation or transforming signals of JAK2-V617F in BaF3 cells. IL27Ra also activated the K539L and R683G JAK2 mutants. Together our data demonstrate that in addition to homodimeric receptors, some heterodimeric receptor components can support the activation and transforming signals of JAK2-V617F and other JAK2 mutants. Therefore, heterodimeric receptors may play unappreciated roles in JAK2 activation in the development of hematopoietic diseases including myeloproliferative neoplasms. PMID- 20363737 TI - Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G. AB - APOBEC3G (hA3G) is a host inhibitor for human immunodeficiency virus, type 1 (HIV 1). However, HIV-1 Vif binds hA3G and induces its degradation. We have established a screening system to discover inhibitors that protect hA3G from Vif mediated degradation. Through screening, compounds IMB-26 and IMB-35 were identified to be specific inhibitors for the degradation of hA3G by Vif. The inhibitors suppressed HIV-1 replication in hA3G-containing cells but not in those without hA3G. The anti-HIV effect correlated with the endogenous hA3G level. HIV 1 particles from hA3G(+) cells treated with IMB-26/35 contained a hA3G level higher than that from those without IMB-26/35 treatment and showed decreased infectivity. IMB-26/35 bound directly to the hA3G protein, suppressed Vif/hA3G interaction, and therefore protected hA3G from Vif-mediated degradation. The compounds were safe with an anti-HIV therapeutic index >200 in vitro. LD(50) of IMB-26 in mice was >1000 mg/kg (intraperitoneally). Therefore, IMB-26 and IMB-35 are novel anti-HIV leads working through specific stabilization of hA3G. PMID- 20363736 TI - Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence. AB - The small GTPase Rab7 promotes fusion events between late endosomes and lysosomes. Rab7 activity is regulated by extrinsic signals, most likely via effects on its guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP). Based on their homology to the yeast proteins that regulate the Ypt7 GTP binding state, TBC1D15, and mammalian Vps39 (mVps39) have been suggested to function as the Rab7 GAP and GEF, respectively. We developed an effector pull down assay to test this model. TBC1D15 functioned as a Rab7 GAP in cells, reducing Rab7 binding to its effector protein RILP, fragmenting the lysosome, and conferring resistance to growth factor withdrawal-induced cell death. In a cellular context, TBC1D15 GAP activity was selective for Rab7. TBC1D15 overexpression did not inhibit transferrin internalization or recycling, Rab7 independent processes that require Rab4, Rab5, and Rab11 activation. TBC1D15 was thus renamed Rab7-GAP. Contrary to expectations for a Rab7 GEF, mVps39 induced lysosomal clustering without increasing Rab7 GTP binding. Moreover, a dominant negative mVps39 mutant fragmented the lysosome and promoted growth factor independence without decreasing Rab7-GTP levels. These findings suggest that a protein other than mVps39 serves as the Rab7 GEF. In summary, although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence. PMID- 20363739 TI - The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein 6 and hepcidin expression in vivo. AB - Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv(-/-)) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv(-/-) mice do not lack BMP6. Furthermore, iron depletion in Hjv(-/-) mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv(-/-) mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling. PMID- 20363738 TI - Amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of Leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases. AB - Leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. Previously, we described a conditional lethal Deltahgprt/Deltaxprt mutant of L. donovani (Boitz, J. M., and Ullman, B. (2006) J. Biol. Chem. 281, 16084-16089) that establishes that L. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and xanthine phosphoribosyltransferase (XPRT). Unlike wild type L. donovani, the Deltahgprt/Deltaxprt knock-out cannot grow on 6-oxypurines and displays an absolute requirement for adenine or adenosine and 2'-deoxycoformycin, an inhibitor of parasite adenine aminohydrolase activity. Here, we demonstrate that the ability of Deltahgprt/Deltaxprt parasites to infect mice was profoundly compromised. Surprisingly, mutant parasites that survived the initial passage through mice partially regained their virulence properties, exhibiting a >10-fold increase in parasite burden in a subsequent mouse infection. To dissect the mechanism by which Deltahgprt/Deltaxprt parasites persisted in vivo, suppressor strains that had regained their capacity to grow under restrictive conditions were cloned from cultured Deltahgprt/Deltaxprt parasites. The ability of these suppressor clones to grow in and metabolize 6-oxypurines could be ascribed to a marked amplification and overexpression of the adenine phosphoribosyltransferase (APRT) gene. Moreover, transfection of Deltahgprt/Deltaxprt cells with an APRT episome recapitulated the suppressor phenotype in vitro and enabled growth on 6 oxypurines. Biochemical studies further showed that hypoxanthine, unexpectedly, was an inefficient substrate for APRT, evidence that could account for the ability of the suppressors to metabolize hypoxanthine. Subsequent analysis implied that APRT amplification was also a potential contributory mechanism by which Deltahgprt/Deltaxprt parasites displayed persistence and increased virulence in mice. PMID- 20363740 TI - Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicry. AB - A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting the cytoskeleton. This is in most cases achieved either by modifying actin, or indirectly via activation of key regulators controlling actin dynamics such as Rho-GTPases. A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. The precise mechanism of nucleotide exchange, however, has remained unclear. Here we report the structure of the WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify IpgB2 as a bacterial RhoA-GEF and dissect the molecular mechanism of GDP release, an essential prerequisite for GTP binding. Our observations uncover that IpgB2 induces conformational changes on RhoA mimicking DbI- but not DOCK family GEFs. We also show that dissociation of the GDP.Mg(2+) complex is preceded by the displacement of the metal ion to the alpha-phosphate of the nucleotide, diminishing its affinity to the GTPase. These data refine our understanding of the mode of action not only of WXXXE GEFs but also of mammalian GEFs of the DH/PH family. PMID- 20363741 TI - Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis. AB - Intestinal fibrosis is a major complication of Crohn disease (CD), but the precise mechanism by which it occurs is incompletely understood. As a result, specific therapies to halt or even reverse fibrosis have not been explored. Here, we evaluated the contribution of epithelial to mesenchymal transition (EMT) to intestinal fibrosis associated with a mouse model of CD and also human inflammatory bowel disease. Mice administered intrarectal 2,4,6-trinitrobenzene sulfonic acid (TNBS) develop inflammation and fibrosis that resembles CD both histologically and by immunologic profile. We utilized this model to molecularly probe the contribution of EMT to intestinal fibrosis. Additionally, we utilized double-transgenic VillinCre;R26Rosa-lox-STOP-lox-LacZ mice, in which removal of the STOP cassette by Cre recombinase in villin(+) intestinal epithelial cells activates permanent LacZ expression, to lineage trace epithelial cells that might undergo EMT upon TNBS administration. TNBS-induced fibrosis is associated with the presence of a significant number of cells that express both epithelial and mesenchymal markers. In the lineage tagged transgenic mice, the appearance of LacZ(+) cells that also express the fibroblast marker FSP1 unequivocally demonstrates EMT. Transforming growth factor (TGF)-beta1, a known inducer of EMT in epithelial cells, induces EMT in rat intestinal epithelial cells in vitro, and bone morphogenic protein-7, an antagonist of TGF-beta1, inhibits EMT and fibrosis both in vitro and in the TNBS-treated mice. Our study demonstrates that EMT contributes to intestinal fibrosis associated with the TNBS-induced model of Crohn colitis and that inhibition of TGF-beta1 with recombinant human bone morphogenic protein-7 prevents this process and prevents fibrosis. PMID- 20363742 TI - Features of a spatially constrained cystine loop in the p10 FAST protein ectodomain define a new class of viral fusion peptides. AB - The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral membrane fusion proteins. With ectodomains of only approximately 20-40 residues, it is unclear how such diminutive fusion proteins can mediate cell-cell fusion and syncytium formation. Contained within the 40 residue ectodomain of the p10 FAST protein resides an 11-residue sequence of moderately apolar residues, termed the hydrophobic patch (HP). Previous studies indicate the p10 HP shares operational features with the fusion peptide motifs found within the enveloped virus membrane fusion proteins. Using biotinylation assays, we now report that two highly conserved cysteine residues flanking the p10 HP form an essential intramolecular disulfide bond to create a cystine loop. Mutagenic analyses revealed that both formation of the cystine loop and p10 membrane fusion activity are highly sensitive to changes in the size and spatial arrangement of amino acids within the loop. The p10 cystine loop may therefore function as a cystine noose, where fusion peptide activity is dependent on structural constraints within the noose that force solvent exposure of key hydrophobic residues. Moreover, inhibitors of cell surface thioreductase activity indicate that disruption of the disulfide bridge is important for p10-mediated membrane fusion. This is the first example of a viral fusion peptide composed of a small, spatially constrained cystine loop whose function is dependent on altered loop formation, and it suggests the p10 cystine loop represents a new class of viral fusion peptides. PMID- 20363743 TI - Extended N-sulfated domains reside at the nonreducing end of heparan sulfate chains. AB - Heparan sulfate (HS) serves as a cell-surface co-receptor for growth factors, morphogens, and chemokines. These HS and protein binding events depend on the fine structure and distribution of domains along an HS chain. A given domain can vary in terms of uronic acid epimer, N- and O-sulfate, and N-acetate content. The most highly sulfated regions of HS chains, N-sulfated (NS) domains, play prominent roles in HS and protein binding. We have analyzed HS oligosaccharides from various mammalian sources and provide evidence that NS domains residing at the nonreducing end (NRE) are, on average, longer than those residing in the internal regions of the chain. Additionally, they are more highly sulfated than their internal counterparts. These features are independent of the sulfation pattern of the bulk HS chains. From disaccharide analysis, it is clear that NS domains do not always occupy HS NREs. However, when they do, they tend to terminate in a subset of N-sulfated disaccharides. Our observations are consistent with a significant role of NRE NS domains in HS-growth factor interactions. PMID- 20363744 TI - Prolyl 3-hydroxylase 1 null mice display abnormalities in fibrillar collagen-rich tissues such as tendons, skin, and bones. AB - Osteogenesis imperfecta (OI) is a skeletal disorder primarily caused by mutations in the type I collagen genes. However, recent investigations have revealed that mutations in the genes encoding for cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1) can cause a severe, recessive form of OI. These reports show minimal 3-hydroxylation of key proline residues in type I collagen as a result of CRTAP or P3H1 deficiency and demonstrate the importance of P3H1 and CRTAP to bone structure and development. P3H1 and CRTAP have previously been shown to form a stable complex with cyclophilin B, and P3H1 was shown to catalyze the 3-hydroxylation of specific proline residues in procollagen I in vitro. Here we describe a mouse model in which the P3H1 gene has been inactivated. Our data demonstrate abnormalities in collagen fibril ultrastructure in tendons from P3H1 null mice by electron microscopy. Differences are also seen in skin architecture, as well as in developing limbs by histology. Additionally bone mass and strength were significantly lower in the P3H1 mice as compared with wild-type littermates. Altogether these investigations demonstrate disturbances of collagen fiber architecture in tissues rich in fibrillar collagen, including bone, tendon, and skin. This model system presents a good opportunity to study the underlying mechanisms of recessive OI and to better understand its effects in humans. PMID- 20363745 TI - Maturation of collagen Ketoimine cross-links by an alternative mechanism to pyridinoline formation in cartilage. AB - The tensile strength of fibrillar collagens depends on stable intermolecular cross-links formed through the lysyl oxidase mechanism. Such cross-links based on hydroxylysine aldehydes are particularly important in cartilage, bone, and other skeletal tissues. In adult cartilages, the mature cross-linking structures are trivalent pyridinolines, which form spontaneously from the initial divalent ketoimines. We examined whether this was the complete story or whether other ketoimine maturation products also form, as the latter are known to disappear almost completely from mature tissues. Denatured, insoluble, bovine articular cartilage collagen was digested with trypsin, and cross-linked peptides were isolated by copper chelation chromatography, which selects for their histidine containing sequence motifs. The results showed that in addition to the naturally fluorescent pyridinoline peptides, a second set of cross-linked peptides was recoverable at a high yield from mature articular cartilage. Sequencing and mass spectral analysis identified their origin from the same molecular sites as the initial ketoimine cross-links, but the latter peptides did not fluoresce and were nonreducible with NaBH(4). On the basis of their mass spectra, they were identical to their precursor ketoimine cross-linked peptides, but the cross linking residue had an M+188 adduct. Considering the properties of an analogous adduct of identical added mass on a glycated lysine-containing peptide from type II collagen, we predicted that similar dihydroxyimidazolidine structures would form from their ketoimine groups by spontaneous oxidation and free arginine addition. We proposed the trivial name arginoline for the ketoimine cross-link derivative. Mature bovine articular cartilage contains about equimolar amounts of arginoline and hydroxylysyl pyridinoline based on peptide yields. PMID- 20363746 TI - Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3. AB - Structural data of integrin alphaIIbbeta3 have been interpreted as supporting a model in which: 1) the receptor exists primarily in a "bent," low affinity conformation on unactivated platelets and 2) activation induces an extended, high affinity conformation prior to, or following, ligand binding. Previous studies found that "clasping" the alphaIIb head domain to the beta3 tail decreased fibrinogen binding. To study the role of alphaIIb extension about the genu, we introduced a disulfide "clamp" between the alphaIIb thigh and calf-1 domains. Clamped alphaIIbbeta3 had markedly reduced ability to bind the large soluble ligands fibrinogen and PAC-1 when activated with monoclonal antibody (mAb) PT25-2 but not when activated by Mn(2+) or by coexpressing the clamped alphaIIb with a beta3 subunit containing the activating mutation N339S. The clamp had little effect on the binding of the snake venom kistrin (M(r) 7,500) or alphaIIbbeta3 mediated adhesion to immobilized fibrinogen, but it did diminish the enhanced binding of mAb AP5 in the presence of kistrin. Collectively, our studies support a role for alphaIIb extension about the genu in the binding of ligands of 340,000 and 900,000 M(r) with mAb-induced activation but indicate that it is not an absolute requirement. Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand. PMID- 20363747 TI - Multiple molecules of Hsc70 and a dimer of DjA1 independently bind to an unfolded protein. AB - Protein folding is a prominent chaperone function of the Hsp70 system. Refolding of an unfolded protein is efficiently mediated by the Hsc70 system with either type 1 DnaJ protein, DjA1 or DjA2, and a nucleotide exchange factor. A surface plasmon resonance technique was applied to investigate substrate recognition by the Hsc70 system and demonstrated that multiple Hsc70 proteins and a dimer of DjA1 initially bind independently to an unfolded protein. The association rate of the Hsc70 was faster than that of DjA1 under folding-compatible conditions. The Hsc70 binding involved a conformational change, whereas the DjA1 binding was bivalent and substoichiometric. Consistently, we found that the bound (14)C labeled Hsc70 to the unfolded protein became more resistant to tryptic digestion. The gel filtration and cross-linking experiments revealed the predominant presence of the DjA1 dimer. Furthermore, the Hsc70 and DjA1 bound to distinct sets of peptide array sequences. All of these findings argue against the generality of the widely proposed hypothesis that the DnaJ-bound substrate is targeted and transferred to Hsp70. Instead, these results suggest the importance of the bivalent binding of DjA1 dimer that limits unfavorable transitions of substrate conformations in protein folding. PMID- 20363748 TI - Characterization of the chemokine CXCL11-heparin interaction suggests two different affinities for glycosaminoglycans. AB - Chemokines orchestrate the migration of leukocytes in the context of homeostasis and inflammation. In addition to interactions of chemokines with receptors on migrating cells, these processes require interactions of chemokines with glycosaminoglycans (GAGs) for cell surface localization. Most chemokines are basic proteins with Arg/Lys/His residue clusters functioning as recognition epitopes for GAGs. In this study we characterized the GAG-binding epitopes of the chemokine I-TAC/CXCL11. Four separate clusters of basic residues were mutated to alanine and tested for their ability to bind to GAGs in vitro and to activate the receptor, CXCR3. Mutation of a set of basic residues in the C-terminal helix (the 50s cluster, (57)KSKQAR(62)) along with Lys(17), significantly impaired heparin binding in vitro, identifying these residues as components of the dominant epitope. However, this GAG mutant retained nearly wild type receptor binding affinity, and its ability to induce cell migration in vitro was only mildly perturbed. Nevertheless, the mutant was unable to induce cell migration in vivo, establishing a requirement of CXCL11 for GAG binding for in vivo function. These studies also led to some interesting findings. First, CXCL11 exhibits conformational heterogeneity, as evidenced by the doubling of peaks in its HSQC spectra. Second, it exhibits more than one affinity state for both heparin and CXCR3, which may be related to its structural plasticity. Finally, although the binding affinities of chemokines for GAGs are typically weaker than interactions with receptors, the high affinity GAG binding state of CXCL11 is comparable with typical receptor binding affinities, suggesting some unique properties of this chemokine. PMID- 20363749 TI - The angiogenic inhibitor long pentraxin PTX3 forms an asymmetric octamer with two binding sites for FGF2. AB - The inflammation-associated long pentraxin PTX3 plays key roles in innate immunity, female fertility, and vascular biology (e.g. it inhibits FGF2 (fibroblast growth factor 2)-mediated angiogenesis). PTX3 is composed of multiple protomers, each composed of distinct N- and C-terminal domains; however, it is not known how these are organized or contribute to its functional properties. Here, biophysical analyses reveal that PTX3 is composed of eight identical protomers, associated through disulfide bonds, forming an elongated and asymmetric, molecule with two differently sized domains interconnected by a stalk. The N-terminal region of the protomer provides the main structural determinant underlying this quaternary organization, supporting formation of a disulfide-linked tetramer and a dimer of dimers (a non-covalent tetramer), giving rise to the asymmetry of the molecule. Furthermore, the PTX3 octamer is shown to contain two FGF2 binding sites, where it is the tetramers that act as the functional units in ligand recognition. Thus, these studies provide a unifying model of the PTX3 oligomer, explaining both its quaternary organization and how this is required for its antiangiogenic function. PMID- 20363750 TI - Acetylation of lysine 564 adjacent to the C-terminal binding protein-binding motif in EVI1 is crucial for transcriptional activation of GATA2. AB - Ecotropic viral integration site 1 (EVI1) is an important transcription factor for leukemogenesis. EVI1 is a member of a group of transcription factors with C terminal binding protein (CtBP)-binding motifs that act as transcriptional co repressors; however, we recently found that EVI1 directly activates GATA2 transcription, which is an important gene for the maintenance of hematopoietic stem cells. We show here that EVI1-activated GATA2 transcripts derive from exon 1S of GATA2, which is specifically activated in neural and hematopoietic cells. EVI1 was acetylated by the histone acetyltransferase p300/CBP association factor (P/CAF) in myeloid leukemia cells and hematopoietic progenitor cells. Acetylation at Lys(564), which is adjacent to the CtBP-binding consensus sequence of EVI1, was found to be important for transcriptional activation of GATA2. Mutation of Lys(564) to alanine (K564A) markedly reduced the ability of EVI1 to bind DNA and activate transcription of GATA2. Furthermore, we confirmed that Lys(564) in EVI1 was specifically acetylated in leukemia and primary hematopoietic cells by using an antibody directed against an acetylated Lys(564) EVI1 peptide. Moreover, co transfection of P/CAF with EVI1 overcame the suppressive effect of the CtBP co repressor and resulted in GATA2 transcriptional activation; nonetheless, CtBP2 was still included in the protein complex with EVI1 and P/CAF on the EVI1-binding site in the GATA2 promoter region. Thus, acetylation of EVI1 at Lys(564) by P/CAF enhances the DNA binding capacity of EVI1 and thereby contributes to the activation of GATA2. PMID- 20363751 TI - Regulation of cardiomyocyte Glut4 expression by ZAC1. AB - The transcription factor ZAC1 is expressed in a variety of tissues including the developing heart, but its physiological role is unclear. We examined the role of ZAC1 in regulating expression of the insulin-responsive glucose transporter GLUT4 and whether ZAC1 expression is altered in cardiomyocyte hypertrophy. We demonstrated expression of Zac1 mRNA and protein in rat cardiomyocytes by PCR and Western blotting, respectively. Using a combination of chromatin immunoprecipitation and luciferase assays, we showed that ZAC1 regulates Glut4 expression via a specific binding site in the Glut4 promoter. Overexpression of ZAC1 increased Glut4 mRNA and protein expression and resulted in increased glucose uptake in cardiomyocytes as determined by a fluorescent analog uptake assay. Induction of hypertrophy by phenylephrine or isoproterenol resulted in increased Zac1 expression. We identified a novel putative promoter in the Zac1 gene and demonstrated increased binding of MEF2 to this promoter in response to hypertrophic stimulation. MEF2 regulated transactivation of the Zac1 promoter and ZAC1 protein expression. This work identifies ZAC1 as a novel and previously unknown regulator of cardiomyocyte Glut4 expression and glucose uptake. Our results also implicate MEF2 as a regulator of ZAC1 expression in response to induction of hypertrophy. PMID- 20363752 TI - Limited compatibility of polymerase subunit interactions in influenza A and B viruses. AB - Despite their close phylogenetic relationship, natural intertypic reassortants between influenza A (FluA) and B (FluB) viruses have not been described. Inefficient polymerase assembly of the three polymerase subunits may contribute to this incompatibility, especially because the known protein-protein interaction domains, including the PA-binding domain of PB1, are highly conserved for each virus type. Here we show that substitution of the FluA PA-binding domain (PB1-A(1 25)) with that of FluB (PB1-B(1-25)) is accompanied by reduced polymerase activity and viral growth of FluA. Consistent with these findings, surface plasmon resonance spectroscopy measurements revealed that PA of FluA exhibits impaired affinity to biotinylated PB1-B(1-25) peptides. PA of FluB showed no detectable affinity to biotinylated PB1-A(1-25) peptides. Consequently, FluB PB1 harboring the PA-binding domain of FluA (PB1-AB) failed to assemble with PA and PB2 into an active polymerase complex. To regain functionality, we used a single amino acid substitution (T6Y) known to confer binding to PA of both virus types, which restored polymerase complex formation but surprisingly not polymerase activity for FluB. Taken together, our results demonstrate that the conserved virus type-specific PA-binding domains differ in their affinity to PA and thus might contribute to intertypic exclusion of reassortants between FluA and FluB viruses. PMID- 20363753 TI - Activation of glucose-6-phosphate dehydrogenase promotes acute hypoxic pulmonary artery contraction. AB - Hypoxic pulmonary vasoconstriction (HPV) is a physiological response to a decrease in airway O(2) tension, but the underlying mechanism is incompletely understood. We studied the contribution of glucose-6-phosphate dehydrogenase (Glc 6-PD), an important regulator of NADPH redox and production of reactive oxygen species, to the development of HPV. We found that hypoxia (95% N(2), 5% CO(2)) increased contraction of bovine pulmonary artery (PA) precontracted with KCl or serotonin. Depletion of extracellular glucose reduced NADPH, NADH, and HPV, substantiating the idea that glucose metabolism and Glc-6-PD play roles in the response of PA to hypoxia. Our data also show that inhibition of glycolysis and mitochondrial respiration (indicated by an increase in NAD(+) and decrease in the ATP-to-ADP ratio) by hypoxia, or by inhibitors of pyruvate dehydrogenase or electron transport chain complexes I or III, increased generation of reactive oxygen species, which in turn activated Glc-6-PD. Inhibition of Glc-6-PD decreased Ca(2+) sensitivity to the myofilaments and diminished Ca(2+) independent and -dependent myosin light chain phosphorylation otherwise increased by hypoxia. Silencing Glc-6-PD expression in PA using a targeted small interfering RNA abolished HPV and decreased extracellular Ca(2+)-dependent PA contraction increased by hypoxia. Similarly, Glc-6-PD expression and activity were significantly reduced in lungs from Glc-6-PD(mut(-/-)) mice, and there was a corresponding reduction in HPV. Finally, regression analysis relating Glc-6-PD activity and the NADPH-to-NADP(+) ratio to the HPV response clearly indicated a positive linear relationship between Glc-6-PD activity and HPV. Based on these findings, we propose that Glc-6-PD and NADPH redox are crucially involved in the mechanism of HPV and, in turn, may play a key role in increasing pulmonary arterial pressure, which is involved in the development of pulmonary hypertension. PMID- 20363754 TI - Protein kinase D controls actin polymerization and cell motility through phosphorylation of cortactin. AB - We here identify protein kinase D (PKD) as an upstream regulator of the F-actin binding protein cortactin and the Arp actin polymerization machinery. PKD phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-S298A protein accelerated VCA-Arp-cortactin-mediated synergistic actin polymerization and showed reduced F-actin binding, indicative of enhanced turnover of nucleation complexes. In vivo, cortactin co-localized with the nucleation promoting factor WAVE2, essential for lamellipodia extension, in the actin polymerization zone in Heregulin-treated MCF-7 cells. Using a 3-dye FRET-based approach we further demonstrate that WAVE2-Arp and cortactin prominently interact at these structures. Accordingly, cortactin-S298A significantly enhanced lamellipodia extension and directed cell migration. Our data thus unravel a previously unrecognized mechanism by which PKD controls cancer cell motility. PMID- 20363755 TI - The protease domain increases the translocation stepping efficiency of the hepatitis C virus NS3-4A helicase. AB - Hepatitis C virus (HCV) NS3 protein has two enzymatic activities of helicase and protease that are essential for viral replication. The helicase separates the strands of DNA and RNA duplexes using the energy from ATP hydrolysis. To understand how ATP hydrolysis is coupled to helicase movement, we measured the single turnover helicase translocation-dissociation kinetics and the pre-steady state P(i) release kinetics on single-stranded RNA and DNA substrates of different lengths. The parameters of stepping were determined from global fitting of the two types of kinetic measurements into a computational model that describes translocation as a sequence of coupled hydrolysis-stepping reactions. Our results show that the HCV helicase moves with a faster rate on single stranded RNA than on DNA. The HCV helicase steps on the RNA or DNA one nucleotide at a time, and due to imperfect coupling, not every ATP hydrolysis event produces a successful step. Comparison of the helicase domain (NS3h) with the protease helicase (NS3-4A) shows that the most significant contribution of the protease domain is to improve the translocation stepping efficiency of the helicase. Whereas for NS3h, only 20% of the hydrolysis events result in translocation, the coupling for NS3-4A is near-perfect 93%. The presence of the protease domain also significantly reduces the stepping rate, but it doubles the processivity. These effects of the protease domain on the helicase can be explained by an improved allosteric cross-talk between the ATP- and nucleic acid-binding sites achieved by the overall stabilization of the helicase domain structure. PMID- 20363756 TI - Multiple mechanisms for elongation processivity within the reconstituted tetrahymena telomerase holoenzyme. AB - To maintain telomeres, telomerase evolved a unique biochemical activity: the use of a single-stranded RNA template for the synthesis of single-stranded DNA repeats. High repeat addition processivity (RAP) of the Tetrahymena telomerase holoenzyme requires association of the catalytic core with the telomere adaptor subcomplex (TASC) and an RPA1-related subunit (p82 or Teb1). Here, we used DNA binding and holoenzyme reconstitution assays to investigate the mechanism by which Teb1 and TASC confer high RAP. We show that TASC association with the recombinant telomerase catalytic core increases enzyme activity. Subsequent association of the Teb1 C-terminal domain with TASC confers the capacity for high RAP even though the Teb1 C-terminal domain does not provide a high-affinity DNA interaction site. Efficient RAP also requires suppression of nascent product folding mediated by the central Teb1 DNA-binding domains (DBDs). These sequence specific high-affinity DBDs of Teb1 can be functionally substituted by the analogous DBDs of Tetrahymena Rpa1 to suppress nascent product folding but only if the Rpa1 high-affinity DBDs are physically tethered into holoenzyme context though the Teb1 C-terminal domain. Overall, our findings reveal multiple mechanisms and multiple surfaces of protein-DNA and protein-protein interaction that give rise to elongation processivity in the synthesis of a single-stranded nucleic acid product. PMID- 20363757 TI - UCP3 translocates lipid hydroperoxide and mediates lipid hydroperoxide-dependent mitochondrial uncoupling. AB - Although the literature contains many studies on the function of UCP3, its role is still being debated. It has been hypothesized that UCP3 may mediate lipid hydroperoxide (LOOH) translocation across the mitochondrial inner membrane (MIM), thus protecting the mitochondrial matrix from this very aggressive molecule. However, no experiments on mitochondria have provided evidence in support of this hypothesis. Here, using mitochondria isolated from UCP3-null mice and their wild type littermates, we demonstrate the following. (i) In the absence of free fatty acids, proton conductance did not differ between wild-type and UCP3-null mitochondria. Addition of arachidonic acid (AA) to such mitochondria induced an increase in proton conductance, with wild-type mitochondria showing greater enhancement. In wild-type mitochondria, the uncoupling effect of AA was significantly reduced both when the release of O2* in the matrix was inhibited and when the formation of LOOH was inhibited. In UCP3-null mitochondria, however, the uncoupling effect of AA was independent of the above mechanisms. (ii) In the presence of AA, wild-type mitochondria released significantly more LOOH compared with UCP3-null mitochondria. This difference was abolished both when UCP3 was inhibited by GDP and under a condition in which there was reduced LOOH formation on the matrix side of the MIM. These data demonstrate that UCP3 is involved both in mediating the translocation of LOOH across the MIM and in LOOH-dependent mitochondrial uncoupling. PMID- 20363758 TI - CtpA, a copper-translocating P-type ATPase involved in the biogenesis of multiple copper-requiring enzymes. AB - The ctpA (ccoI) gene product, a putative inner membrane copper-translocating P1B type ATPase present in many bacteria, has been shown to be involved only in the cbb(3) assembly in Rhodobacter capsulatus and Bradyrhizobium japonicum. ctpA was disrupted in Rubrivivax gelatinosus, and the mutants showed a drastic decrease in both cbb(3) and caa(3) oxidase activities. Inactivation of ctpA results also in a decrease in the amount of the nitrous oxide reductase, NosZ. This pleiotropic phenotype could be partially rescued by excess copper in the medium, indicating that CtpA is likely a copper transporter that supplies copper-requiring proteins in the membrane with this metal. Although CtpA shares significant sequence homologies with the homeostasis copper efflux P1B-type ATPases including the bacterial CopA and the human ATP7A and ATP7B, disruption of ctpA did not result in any sensitivity to excess copper. This indicates that the CtpA is not crucial for copper tolerance but is involved in the assembly of membrane and periplasmic copper enzymes in this bacterium. The potential roles of CtpA in bacteria in comparison with CopA are discussed. PMID- 20363760 TI - Complex distribution patterns, ecology and coexistence of ploidy levels of Allium oleraceum (Alliaceae) in the Czech Republic. AB - BACKGROUND AND AIMS: Despite extensive study of polyploidy, its origin, and ecogeographical differences between polyploids and their diploid progenitors, few studies have addressed ploidy-level structure and patterns of ecogeographical differentiation at various spatial scales using detailed sampling procedures. The pattern of coexistence of polyploids in the geophyte Allium oleraceum at the landscape and locality scale and their ecology were studied. METHODS: Flow cytometry and root-tip squashes were used to identify the ploidy level of 4347 plants from 325 populations sampled from the Czech Republic using a stratified random sampling procedure. Ecological differentiation among ploidy levels was tested by comparing sets of environmental variables recorded at each locality. KEY RESULTS: Across the entire sampling area, pentaploids (2n = 5x = 40) predominated, while hexaploids (2n = 6x = 48) and tetraploids (2n = 4x = 32) were less frequent. The distribution of tetra- and hexaploids was partially sympatric (in the eastern part) to parapatric (in the western part of the Czech Republic) whereas pentaploids were sympatric with other cytotypes. Plants of different ploidy levels were found to be ecologically differentiated and the ruderal character of cytotypes increased in the direction 4x --> 5x --> 6x with the largest realized niche differences between tetra- and hexaploids. Most populations contained only one ploidy level (77 %), 22 % had two (all possible combinations) and 1 % were composed of three ploidy levels. The majority of 4x + 5x and 5x + 6x mixed populations occurred in sympatry with uniform populations of the participating cytotypes in sites with ecologically heterogeneous or marginal environment, suggesting secondary contact between cytotypes. Some mixed 4x + 6x populations dominated by tetraploids being sympatric and intermixed with uniform 4x populations might represent primary zones of cytotype contact. Almost no mixed accessions were observed on the fine spatial scale in mixed populations. CONCLUSIONS: The results provide evidence for adaptive differences among ploidy levels, which may contribute to their complex distribution pattern. The prevalence of asexual reproduction, limited dispersal and equilibrium-disrupting processes may support local coexistence of cytotypes. PMID- 20363759 TI - Solution conformation and dynamics of the HIV-1 integrase core domain. AB - The human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a critical enzyme involved in infection. It catalyzes two reactions to integrate the viral cDNA into the host genome, 3' processing and strand transfer, but the dynamic behavior of the active site during catalysis of these two processes remains poorly characterized. NMR spectroscopy can reveal important structural details about enzyme mechanisms, but to date the IN catalytic core domain has proven resistant to such an analysis. Here, we present the first NMR studies of a soluble variant of the catalytic core domain. The NMR chemical shifts are found to corroborate structures observed in crystals, and confirm prior studies suggesting that the alpha4 helix extends toward the active site. We also observe a dramatic improvement in NMR spectra with increasing MgCl(2) concentration. This improvement suggests a structural transition not only near the active site residues but also throughout the entire molecule as IN binds Mg(2+). In particular, the stability of the core domain is linked to the conformation of its C-terminal helix, which has implications for relative domain orientation in the full-length enzyme. (15)N relaxation experiments further show that, although conformationally flexible, the catalytic loop of IN is not fully disordered in the absence of DNA. Indeed, automated chemical shift-based modeling of the active site loop reveals several stable clusters that show striking similarity to a recent crystal structure of prototype foamy virus IN bound to DNA. PMID- 20363761 TI - Primary sources and immunological prerequisites for sST2 secretion in humans. AB - AIMS: Serum levels of the soluble growth stimulation gene-2 (sST2) are elevated in heart and pulmonary diseases. However, the relationship of the sST2/interleukin (IL)-33 axis and its triggers as well as its organ distribution is still not known. This study was thus designed to investigate the cellular origin and regulation of sST2 and IL-33 in vitro and in vivo. METHODS AND RESULTS: sST2 and IL-33 gene expression and protein secretion were analysed in pooled organ-specific cDNAs and in primary cell cultures, respectively, by RT-PCR and ELISA technology. The strongest sST2 mRNA expression was detected in heart and lung tissues, which correlated with spontaneous secretion of sST2 protein in vitro. The inflammatory cytokines IL-1alpha, IL-1beta, and tumour necrosis factor alpha as well as supernatants of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells led to an enhanced secretion of sST2 in cultured cardiac myocytes and lung alveolar epithelial cells. These cytokines enhanced sST2 secretion via an NFkappaB-dependent mechanism. In addition, LPS stimulation in humans in vivo induced a short-term inflammatory response that was followed by a massive enhancement of sST2 secretion. CONCLUSION: These results identify the primary sources and inflammatory triggers for the enhancement of sST2 secretion and demonstrate a relationship between inflammation and the secretion of a bioactive member of the IL-1R family, both in vitro and in vivo. PMID- 20363762 TI - Revised non-contact mapping of ventricular scar in a post-infarct ovine model with validation using contact mapping and histology. AB - AIMS: Identification of arrhythmogenic scar using non-contact (NC) sinus rhythm (SR) mapping is limited. Dynamic substrate mapping (DSM) overcomes these limitations but is less accurate than plunge needle electrode mapping. We developed a revised method for calculating DSM which was validated using detailed histological analysis and compared with conventional mapping modalities. METHODS AND RESULTS: Mapping was performed in eight sheep, >9 weeks post-myocardial infarction. Twenty multielectrode needles were deployed at thoracotomy in the left ventricle within and surrounding scar, and located using Ensite. Simultaneous catheter, needle, and NC electrograms were recorded during SR and multisite pacing. Dynamic substrate mapping maps were calculated as the maximum local peak negative voltage (PNV). Absolute mean DSM (AMDSM) maps, based on peak peak voltage (P-PV), were calculated to minimize local pacing effects and take into account anisotropic influence. Dynamic substrate mapping and AMDSM maps were normalized based on global maximum voltages attained. Histologically quantified scar and mapping criteria were compared using Spearman's correlation and receiver operator curves (area under the curve, AUC) using 50% scar cut-off. For unipolar mapping, needles had greatest sensitivity at identifying scar which was better for P-PV (AUC; needle = 0.90, catheter = 0.70, NC = 0.66) than for PNV (AUC; needle = 0.79, NC = 0.38). AMDSM (AUC = 0.75) had superior scar discrimination than either catheter (AUC; unipolar = 0.70, bipolar = 0.71) or DSM (AUC = 0.67). Absolute mean DSM accuracy was improved when valvular geometries were excluded (AUC = 0.77). CONCLUSION: Absolute mean DSM was comparably accurate in identifying scarred myocardium as PNV needle mapping but was superior to conventional catheter and NC mapping. PMID- 20363763 TI - Atrio-ventricular conduction following radiofrequency ablation for atrio ventricular node reentry tachycardia in children. AB - AIMS: The study was designed to assess atrio-ventricular (AV) conduction with non invasive methods at least 1 year after radiofrequency ablation (RFA) of the slow pathway for AV node reentry tachycardia. METHODS AND RESULTS: Medical records of all patients who underwent RFA before their 18th birthday were reviewed. Patients were brought back for clinical evaluation, an electrocardiogram, an exercise stress test, and ambulatory Holter monitoring. Radiofrequency ablation of the slow pathway above the ostium of the coronary sinus was done in 106 children. No procedure resulted in high degree AV block. Follow-up evaluation was possible in 67 patients (63% of the total cohort) who were brought back to the clinic 1-13.7 years, mean 4.7+/-3.0 years after the procedure. Dizzy spells were reported by 36% of examined patients and 2 patients reported syncope. PR intervals were normal in all but two patients when compared with published normal values. One patient presented with persistent, post-procedural first-degree AV block and another developed new onset, symptomatic second degree AV block 2 years after the procedure and required pacemaker implantation. CONCLUSION: Non-invasive testing showed normal PR intervals in a cohort of patients who underwent RFA of the slow pathway in childhood or adolescence. Late AV block occurred in one child. Clinical evaluation more than a year after the procedure is warranted in symptomatic patients. PMID- 20363764 TI - Clopidogrel reloading in patients undergoing percutaneous coronary intervention on chronic clopidogrel therapy: results of the ARMYDA-4 RELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) randomized trial. AB - AIMS: To evaluate safety and effectiveness of clopidogrel reloading in patients on chronic clopidogrel therapy undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Five hundred and three patients on >10 days clopidogrel therapy (41% with non-ST-segment elevation acute coronary syndrome, ACS) randomly received 600 mg clopidogrel loading 4-8 h before PCI (n = 252) or placebo (n = 251). Primary endpoint was 30-day incidence of major adverse cardiac events (MACE). In the overall population primary endpoint occurred in 6.7% of patients in the reload vs. 8.8% in the placebo arm [odds ratios (OR) 0.75, 95% confidence intervals (CI) 0.37-1.52; P = 0.50]. In stable angina patients, 1 month MACE were not significantly different (7.0 vs. 3.9%; OR 1.84, 0.60-5.88; P = 0.36), whereas ACS patients had significant clinical benefit with reloading (6.4 vs. 16.3%; OR 0.34, 95% CI 0.32-0.90, P = 0.033 at multivariable analysis; interaction test: P = 0.01). There was no excess bleeding in the reload arm (6% in both groups). CONCLUSION: ARMYDA-4 RELOAD reveals no overall benefit from reloading patients on chronic clopidogrel therapy prior to PCI; the benefit observed in ACS patients is a hypothesis-generating finding that needs to be confirmed by larger studies. PMID- 20363765 TI - The fate of incomplete stent apposition with drug-eluting stents: an optical coherence tomography-based natural history study. AB - AIMS: To assess the fate of incomplete stent apposition (ISA) after deployment of sirolimus-eluting stents (SESs). METHODS AND RESULTS: Thirty-two patients having intravascular ultrasound (IVUS)-guided PCI with SESs underwent assessment of stent deployment with quantitative coronary angiography, IVUS, and optical coherence tomography (OCT) pre-procedure, post-procedure, and at 10 months follow up. Incomplete stent apposition was defined as separation of a stent strut from the inner vessel wall by >160 microm. At follow-up, 4.67% of struts with ISA at deployment failed to heal and 7.59% which were well apposed did not develop neointimal hyperplasia even after 10 months. Lesion remodelling was responsible for the development of late ISA in only 0.37% of struts. Failure of adequate neointimal hyperplasia was quantitatively the most important mechanism responsible for persistent acute ISA, classified in previous studies, which relied only on follow-up OCT, as late ISA. Thrombus was visualized in 20.6% of struts with ISA at follow-up and in 2.0% of struts with a good apposition (P < 0.001). CONCLUSION: In patients with SESs, ISA can fail to heal and even complete apposition can be associated with no neointimal hyperplasia. Incomplete stent apposition without neointimal hyperplasia was significantly associated with the presence of OCT-detected thrombus at follow-up, and may constitute a potent substrate for late stent thrombosis. PMID- 20363766 TI - Is it naive to load only clopidogrel-naive patients prior to PCI? PMID- 20363767 TI - "Worse than being married": the exodus of British doctors from the National Health Service to Canada, c. 1955-75. AB - Despite a sizeable literature on the evolution of health insurance in Britain and Canada, there is virtually no research on the transnational migration of physicians between these countries in the immediate postwar period. This article hopes to address this neglected subject. Three inter-related topics will be examined. First, the paper will summarize the debate over physician emigration from the National Health Service (NHS) in postwar Britain. It will demonstrate how British social scientists and politicians began to come to grips with a major demographic exodus of British-trained doctors in the late 1950s and early 1960s. Second, it will analyze the changing health human resource situation in 1960s Canada, which focused, for practical and cultural reasons, on General Medical Council of Britain licensed practitioners. Third, through oral interviews of British-trained physicians who settled in Canada during the 1960s, it will examine the professional and personal reasons why physicians left Britain for Canada. It reveals that, among a myriad of personal issues that motivated a physician to leave the NHS, the inflexibility and hierarchical nature of British medicine loomed very large. The paper will conclude by reflecting on the contemporary significance of this fascinating historical phenomenon. PMID- 20363768 TI - Bevacizumab in recurrent high-grade pediatric gliomas. AB - Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference. PMID- 20363769 TI - Improved survival of left-sided pancreas cancer after surgery. AB - OBJECTIVE: Resective therapeutic strategy for left-sided pancreatic adenocarcinoma is open to debate. The post-resection outcomes and factors influencing post-resection survival for adenocarcinoma of the body and tail of the pancreas were analyzed to determine the effectiveness of surgery. METHODS: A total of 73 patients with adenocarcinoma of the body or tail of the pancreas who underwent resection between 1994 and June 2007 were evaluated for overall survival. RESULTS: Multiple malignancies were present in 34 of 73 patients (47%). Overall 1-, 3- and 5-year survival rates after surgery were 79%, 34%, and 30%, respectively. Presence of symptoms, multiple cancers and level of preoperative tumor marker did not influence post-resection survival. As for tumor characteristics, tumor size, histological tumor differentiation, retroperitoneal invasion, status of residual tumor and UICC staging represented significant prognostic indicators by univariate analysis. Gemcitabine, when administered as an adjuvant settings, strongly worked for improving post-resection outcome (5 year survival rate = 51%). Factors shown to have independent prognostic significance on multivariate analysis were tumor size (<3 vs. >or=3 cm), status of residual tumor (R0 vs. R1, 2), and postoperative administration of gemcitabine. CONCLUSIONS: Appropriate patient selection and accurate surgical technique with postoperative adjuvant therapy could benefit survival of patients with carcinoma of the pancreas body and tail. PMID- 20363770 TI - A genetic framework for grain size and shape variation in wheat. AB - Grain morphology in wheat (Triticum aestivum) has been selected and manipulated even in very early agrarian societies and remains a major breeding target. We undertook a large-scale quantitative analysis to determine the genetic basis of the phenotypic diversity in wheat grain morphology. A high-throughput method was used to capture grain size and shape variation in multiple mapping populations, elite varieties, and a broad collection of ancestral wheat species. This analysis reveals that grain size and shape are largely independent traits in both primitive wheat and in modern varieties. This phenotypic structure was retained across the mapping populations studied, suggesting that these traits are under the control of a limited number of discrete genetic components. We identified the underlying genes as quantitative trait loci that are distinct for grain size and shape and are largely shared between the different mapping populations. Moreover, our results show a significant reduction of phenotypic variation in grain shape in the modern germplasm pool compared with the ancestral wheat species, probably as a result of a relatively recent bottleneck. Therefore, this study provides the genetic underpinnings of an emerging phenotypic model where wheat domestication has transformed a long thin primitive grain to a wider and shorter modern grain. PMID- 20363771 TI - miR390, Arabidopsis TAS3 tasiRNAs, and their AUXIN RESPONSE FACTOR targets define an autoregulatory network quantitatively regulating lateral root growth. AB - Plants adapt to different environmental conditions by constantly forming new organs in response to morphogenetic signals. Lateral roots branch from the main root in response to local auxin maxima. How a local auxin maximum translates into a robust pattern of gene activation ensuring the proper growth of the newly formed lateral root is largely unknown. Here, we demonstrate that miR390, TAS3 derived trans-acting short-interfering RNAs (tasiRNAs), and AUXIN RESPONSE FACTORS (ARFs) form an auxin-responsive regulatory network controlling lateral root growth. Spatial expression analysis using reporter gene fusions, tasi/miRNA sensors, and mutant analysis showed that miR390 is specifically expressed at the sites of lateral root initiation where it triggers the biogenesis of tasiRNAs. These tasiRNAs inhibit ARF2, ARF3, and ARF4, thus releasing repression of lateral root growth. In addition, ARF2, ARF3, and ARF4 affect auxin-induced miR390 accumulation. Positive and negative feedback regulation of miR390 by ARF2, ARF3, and ARF4 thus ensures the proper definition of the miR390 expression pattern. This regulatory network maintains ARF expression in a concentration range optimal for specifying the timing of lateral root growth, a function similar to its activity during leaf development. These results also show how small regulatory RNAs integrate with auxin signaling to quantitatively regulate organ growth during development. PMID- 20363772 TI - Identification of specific DNA binding residues in the TCP family of transcription factors in Arabidopsis. AB - The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an approximately 60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors. PMID- 20363773 TI - Arabidopsis histidine kinase CKI1 acts upstream of histidine phosphotransfer proteins to regulate female gametophyte development and vegetative growth. AB - Cytokinin signaling is mediated by a multiple-step phosphorelay. Key components of the phosphorelay consist of the histidine kinase (HK)-type receptors, histidine phosphotransfer proteins (HP), and response regulators (RRs). Whereas overexpression of a nonreceptor-type HK gene CYTOKININ-INDEPENDENT1 (CKI1) activates cytokinin signaling by an unknown mechanism, mutations in CKI1 cause female gametophytic lethality. However, the function of CKI1 in cytokinin signaling remains unclear. Here, we characterize a mutant allele, cki1-8, that can be transmitted through female gametophytes with low frequency (approximately 0.17%). We have recovered viable homozygous cki1-8 mutant plants that grow larger than wild-type plants, show defective megagametogenesis and rarely set enlarged seeds. We found that CKI1 acts upstream of AHP (Arabidopsis HP) genes, independently of cytokinin receptor genes. Consistently, an ahp1,2-2,3,4,5 quintuple mutant, which contains an ahp2-2 null mutant allele, exhibits severe defects in megagametogenesis, with a transmission efficiency of <3.45% through female gametophytes. Rarely recovered ahp1,2-2,3,4,5 quintuple mutants are seedling lethal. Finally, the female gametophytic lethal phenotype of cki1-5 (a null mutant) can be partially rescued by IPT8 or ARR1 (a type-B Arabidopsis RR) driven by a CKI1 promoter. These results define a genetic pathway consisting of CKI1, AHPs, and type-B ARRs in the regulation of female gametophyte development and vegetative growth. PMID- 20363774 TI - Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. AB - Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development. PMID- 20363775 TI - In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder. AB - B-cell lymphoma is a clonal expansion of neoplastic cells that may result in fatal outcomes. Here, we report the in vivo targeting and growth inhibition of aggressive A20 murine B-cell lymphoma by idiotype-specific peptide pA20-36. pA20 36 was selected from random peptide libraries and bound specifically to the B cell receptor (BCR) of A20 cells in mice engrafted with A20 lymphoma, as shown by histology and positron emission tomographic analysis. BCR cross-linking of A20 cells with pA20-36 resulted in massive apoptosis of targeted tumor cells and in an increased survival of the diseased animals without any detectable evidence of toxicity. The pA20-36 treatment reverted the immune suppression of the tumor microenvironment as shown by reduced expression of vascular endothelial growth factor, interleukin-10, and transforming growth factor-beta cytokines together with a lower number of CD11b+Gr-1+ inhibitor myeloid-derived suppressor cells and Foxp3+CD4+ Treg cells. Furthermore, pA20-36 treatment was associated with an increased number of tumor-infiltrating, activated CD8+ T cells that exerted a tumor-specific cytolytic activity. These findings show that a short peptide that binds specifically to the complementarity-determining regions of the A20 BCR allows in vivo detection of neoplastic cells together with significant inhibition of tumor growth in vivo. PMID- 20363776 TI - Comparison of culture methods for isolation of nontuberculous mycobacteria from surface waters. AB - The environment is the likely source of most nontuberculous mycobacteria (NTM) involved in human infections, especially pulmonary, skin, and soft tissue infections. In order to measure the prevalence of NTM in different aquatic ecosystems, we tried to standardize the culture methods used for surface water testing since many procedures have been described previously. Cultivation of mycobacteria requires long-term incubation in rich media and inactivation of rapidly growing microorganisms whose growth impedes observation of mycobacterial colonies. Consequently, the two criteria used for evaluation of the methods examined were (i) the rate of inhibition of nontarget microorganisms and (ii) the efficiency of recovery of mycobacteria. We compared the competitive growth of Mycobacterium chelonae and M. avium with nontarget microorganisms on rich Middlebrook 7H11-mycobactin medium after treatment by several chemical decontamination methods that included acids, bases, detergent, or cetylpyridinium chloride (CPC) with and without an antibiotic cocktail, either PANTA (40 U/ml polymyxin, 4 microg/ml amphotericin B, 16 microg/ml nalidixic acid, 4 microg/ml trimethoprim, and 4 microg/ml azlocillin) or PANTAV (PANTA plus 10 microg/ml vancomycin). Our results showed that treatment for 30 min with CPC (final concentration, 0.05%) of water concentrated by centrifugation, followed by culture on a rich medium supplemented with PANTA, significantly decreased the growth of nontarget microorganisms (the concentrations were 6.2 +/- 0.4 log(10) CFU/liter on Middlebrook 7H11j medium and 4.2 +/- 0.2 log(10) CFU/liter on Middlebrook 7H11j medium containing PANTA [P < 0.001]), while the effect of this procedure on NTM was not as great (the concentrations of M. chelonae on the two media were 7.0 +/- 0.0 log(10) CFU/liter and 6.9 +/- 0.0 log(10) CFU/liter, respectively, and the concentrations of M. avium were 9.1 +/- 0.0 log(10) CFU/liter and 8.9 +/- 0.0 log(10) CFU/liter, respectively). We propose that this standardized culture procedure could be used for detection of NTM in aquatic samples. PMID- 20363777 TI - Application of Fourier transform infrared spectroscopy and chemometrics for differentiation of Salmonella enterica serovar Enteritidis phage types. AB - Fourier transform infrared (FT-IR) spectroscopy and chemometric techniques were used to discriminate five closely related Salmonella enterica serotype Enteritidis phage types, phage type 1 (PT1), PT1b, PT4b, PT6, and PT6a. Intact cells and outer membrane protein (OMP) extracts from bacterial cell membranes were subjected to FT-IR analysis in transmittance mode. Spectra were collected over a wavenumber range from 4,000 to 600 cm(-1). Partial least-squares discriminant analysis (PLS-DA) was used to develop calibration models based on preprocessed FT-IR spectra. The analysis based on OMP extracts provided greater separation between the Salmonella Enteritidis PT1-PT1b, PT4b, and PT6-PT6a groups than the intact cell analysis. When these three phage type groups were considered, the method based on OMP extract FT-IR spectra was 100% accurate. Moreover, complementary local models that considered only the PT1-PT1b and PT6 PT6a groups were developed, and the level of discrimination increased. PT1 and PT1b isolates were differentiated successfully with the local model using the entire OMP extract spectrum (98.3% correct predictions), whereas the accuracy of discrimination between PT6 and PT6a isolates was 86.0%. Isolates belonging to different phage types (PT19, PT20, and PT21) were used with the model to test its robustness. For the first time it was demonstrated that FT-IR analysis of OMP extracts can be used for construction of robust models that allow fast and accurate discrimination of different Salmonella Enteritidis phage types. PMID- 20363778 TI - Interplay between iron homeostasis and the osmotic stress response in the halophilic bacterium Chromohalobacter salexigens. AB - In this study, the connection between iron homeostasis and the osmostress response in the halophile Chromohalobacter salexigens was investigated. A decrease in the requirement for both iron and histidine and a lower level of siderophore synthesis were observed at high salinity, and these findings were correlated with a lower protein content in salt-stressed cells. A six-gene operon (cfuABC-fur-hisI-orf6 operon) located downstream of the ectABC ectoine synthesis genes was characterized. A fur strain (in which the ferric iron uptake regulator Fur was affected) had the Mn resistance phenotype typical of fur mutants, was deregulated for siderophore production, and displayed delayed growth under iron limitation conditions, indicating that fur encodes a functional iron regulator. hisI was essential for histidine synthesis, which in turn was necessary for siderophore production. Fur boxes were found in the promoters of the cfuABC-fur hisI-orf6 and ectABC operons, suggesting that Fur directly interacts with DNA in these regions. Fur mediated the osmoregulated inhibition of cfuABC-fur-hisI-orf6 operon expression by iron and functioned as a positive regulator of the ectABC genes under high-salinity conditions, linking the salt stress response with iron homeostasis. Excess iron led to a higher cytoplasmic hydroxyectoine content, suggesting that hydroxyectoine protects against the oxidative stress caused by iron better than ectoine. This study provides the first evidence of involvement of the iron homeostasis regulator Fur as part of the complex circuit that controls the response to osmotic stress in halophilic bacteria. PMID- 20363779 TI - Double-blind characterization of non-genome-sequenced bacteria by mass spectrometry-based proteomics. AB - Due to the possibility of a biothreat attack on civilian or military installations, a need exists for technologies that can detect and accurately identify pathogens in a near-real-time approach. One technology potentially capable of meeting these needs is a high-throughput mass spectrometry (MS)-based proteomic approach. This approach utilizes the knowledge of amino acid sequences of peptides derived from the proteolysis of proteins as a basis for reliable bacterial identification. To evaluate this approach, the tryptic digest peptides generated from double-blind biological samples containing either a single bacterium or a mixture of bacteria were analyzed using liquid chromatography tandem mass spectrometry. Bioinformatic tools that provide bacterial classification were used to evaluate the proteomic approach. Results showed that bacteria in all of the double-blind samples were accurately identified with no false-positive assignment. The MS proteomic approach showed strain-level discrimination for the various bacteria employed. The approach also characterized double-blind bacterial samples to the respective genus, species, and strain levels when the experimental organism was not in the database due to its genome not having been sequenced. One experimental sample did not have its genome sequenced, and the peptide experimental record was added to the virtual bacterial proteome database. A replicate analysis identified the sample to the peptide experimental record stored in the database. The MS proteomic approach proved capable of identifying and classifying organisms within a microbial mixture. PMID- 20363780 TI - Broad-host-range plasmids for red fluorescent protein labeling of gram-negative bacteria for use in the zebrafish model system. AB - To observe real-time interactions between green fluorescent protein-labeled immune cells and invading bacteria in the zebrafish (Danio rerio), a series of plasmids was constructed for the red fluorescent protein (RFP) labeling of a variety of fish and human pathogens. The aim of this study was to create a collection of plasmids that would express RFP pigments both constitutively and under tac promoter regulation and that would be nontoxic and broadly transmissible to a variety of Gram-negative bacteria. DNA fragments encoding the RFP dimeric (d), monomeric (m), and tandem dimeric (td) derivatives d-Tomato, td Tomato, m-Orange, and m-Cherry were cloned into the IncQ-based vector pMMB66EH in Escherichia coli. Plasmids were mobilized into recipient strains by conjugal mating. Pigment production was inducible in Escherichia coli, Pseudomonas aeruginosa, Edwardsiella tarda, and Vibrio (Listonella) anguillarum strains by isopropyl-beta-d-thiogalactopyranoside (IPTG) treatment. A spontaneous mutant exconjugant of P. aeruginosa PA14 was isolated that expressed td-Tomato constitutively. Complementation analysis revealed that the constitutive phenotype likely was due to a mutation in lacI(q) carried on pMMB66EH. DNA sequence analysis confirmed the presence of five transitions, four transversions, and a 2 bp addition within a 14-bp region of lacI. Vector DNA was purified from this constitutive mutant, and structural DNA sequences for RFP pigments were cloned into the constitutive vector. Exconjugants of P. aeruginosa, E. tarda, and V. anguillarum expressed all pigments in an IPTG-independent fashion. Results from zebrafish infectivity studies indicate that RFP-labeled pathogens will be useful for the study of real-time interactions between host cells of the innate immune system and the infecting pathogen. PMID- 20363781 TI - Single-cell techniques using chromosomally tagged fluorescent bacteria to study Listeria monocytogenes infection processes. AB - Listeria monocytogenes is a Gram-positive facultative intracellular pathogen which invades different cell types, including nonphagocytic cells, where it is able to replicate and survive. The different steps of the cellular infectious process have been well described and consist of bacterial entry, lysis of the endocytic vacuole, intracellular replication, and spreading to neighboring cells. To study the listerial infectious process, gentamicin survival assays, plaque formation, and direct microscopy observations are typically used; however, there are some caveats with each of these techniques. In this study we describe new single-cell techniques based on use of an array of integrative fluorescent plasmids (green, cyan, and yellow fluorescent proteins) to easily, rapidly, and quantitatively detect L. monocytogenes in vitro and in vivo. We describe construction of 13 integrative and multicopy plasmids which can be used for detecting intracellular bacteria, for measuring invasion, cell-to-cell spreading, and intracellular replication, for monitoring in vivo infections, and for generating transcriptional or translational reporters. Furthermore, we tested these plasmids in a variety of epifluorescence- and flow cytometry-based assays. We showed that we could (i) determine the expression of a particular promoter during the cell cycle, (ii) establish in one rapid experiment at which step in the cell cycle a particular mutant is defective, and (iii) easily measure the number of infected cells in vitro and in mouse organs. The plasmids that are described and the methods to detect them are new powerful tools to study host Listeria interactions in a fast, robust, and high-throughput manner. PMID- 20363782 TI - Comparison of genotypes of Salmonella enterica serovar Enteritidis phage type 30 and 9c strains isolated during three outbreaks associated with raw almonds. AB - In 2000 to 2001, 2003 to 2004, and 2005 to 2006, three outbreaks of Salmonella enterica serovar Enteritidis were linked with the consumption of raw almonds. The S. Enteritidis strains from these outbreaks had rare phage types (PT), PT30 and PT9c. Clinical and environmental S. Enteritidis strains were subjected to pulsed field gel electrophoresis (PFGE), multilocus variable-number tandem repeat analysis (MLVA), and DNA microarray-based comparative genomic indexing (CGI) to evaluate their genetic relatedness. All three methods differentiated these S. Enteritidis strains in a manner that correlated with PT. The CGI analysis confirmed that the majority of the differences between the S. Enteritidis PT9c and PT30 strains corresponded to bacteriophage-related genes present in the sequenced genomes of S. Enteritidis PT4 and S. enterica serovar Typhimurium LT2. However, PFGE, MLVA, and CGI failed to discriminate between S. Enteritidis PT30 strains related to outbreaks from unrelated clinical strains or between strains separated by up to 5 years. However, metabolic fingerprinting demonstrated that S. Enteritidis PT4, PT8, PT13a, and clinical PT30 strains metabolized L-aspartic acid, L-glutamic acid, L-proline, L-alanine, and D-alanine amino acids more efficiently than S. Enteritidis PT30 strains isolated from orchards. These data indicate that S. Enteritidis PT9c and 30 strains are highly related genetically and that PT30 orchard strains differ from clinical PT30 strains metabolically, possibly due to fitness adaptations. PMID- 20363783 TI - Involvement of the mannose phosphotransferase system of Lactobacillus plantarum WCFS1 in peroxide stress tolerance. AB - A Lactobacillus plantarum strain with a deletion in the gene rpoN, encoding the alternative sigma factor 54 (sigma(54)), displayed a 100-fold-higher sensitivity to peroxide than its parental strain. This feature could be due to sigma(54) dependent regulation of genes involved in the peroxide stress response. However, transcriptome analyses of the wild type and the mutant strain during peroxide exposure did not support such a role for sigma(54). Subsequent experiments revealed that the impaired expression of the mannose phosphotransferase system (PTS) operon in the rpoN mutant caused the observed increased peroxide sensitivity. PMID- 20363784 TI - A predominant multidrug-resistant Salmonella enterica serovar Saintpaul clonal line in German turkey and related food products. AB - Recently, Salmonella enterica subsp. enterica serovar Saintpaul has increasingly been observed in several countries, including Germany. However, the pathogenic potential and epidemiology of this serovar are not very well known. This study describes biological attributes of S. Saintpaul isolates obtained from turkeys in Germany based on characterization of their pheno- and genotypic properties. Fifty five S. Saintpaul isolates from German turkeys and turkey-derived food products isolated from 2000 to 2007 were analyzed by using antimicrobial agent, organic solvent, and disinfectant susceptibility tests, isoelectric focusing, detection of resistance determinants, plasmid profiling, pulsed-field gel electrophoresis (PFGE), and hybridization experiments. These isolates were compared to an outgroup consisting of 24 S. Saintpaul isolates obtained from humans and chickens in Germany and from poultry and poultry products (including turkeys) in Netherlands. A common core resistance pattern was detected for 27 German turkey and turkey product isolates. This pattern included resistance (full or intermediate) to ampicillin, amoxicillin-clavulanic acid, gentamicin, kanamycin, nalidixic acid, streptomycin, spectinomycin, and sulfamethoxazole and intermediate resistance or decreased susceptibility to ciprofloxacin (MIC, 2 or 1 mug/ml, respectively) and several third-generation cephalosporins (including ceftiofur and cefoxitin [MIC, 4 to 2 and 16 to 2 mug/ml, respectively]). These isolates had the same core resistance genotype, with bla(TEM-1), aadB, aadA2, sul1, a Ser83-->Glu83 mutation in the gyrA gene, and a chromosomal class 1 integron carrying the aadB-aadA2 gene cassette. Their XbaI, BlnI, and combined XbaI-BlnI PFGE patterns revealed levels of genetic similarity of 93, 75, and 90%, respectively. This study revealed that a multiresistant S. Saintpaul clonal line is widespread in turkeys and turkey products in Germany and was also detected among German human fecal and Dutch poultry isolates. PMID- 20363785 TI - Novel technique for quantifying adhesion of Metarhizium anisopliae conidia to the tick cuticle. AB - The present study describes an accurate quantitative method for quantifying the adherence of conidia to the arthropod cuticle and the dynamics of conidial germination on the host. The method was developed using conidia of Metarhizium anisopliae var. anisopliae (Metschn.) Sorokin (Hypocreales: Clavicipitaceae) and engorged Rhipicephalus annulatus (Say) (Arachnida: Ixodidae) females and was also verified for M. anisopliae var. acridum Driver et Milner (Hypocreales: Clavicipitaceae) and Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) larvae. This novel method is based on using an organic solvent (dichloromethane [DCM]) to remove the adhered conidia from the tick cuticle, suspending the conidia in a detergent solution, and then counting them using a hemocytometer. To confirm the efficacy of the method, scanning electron microscopy (SEM) was used to observe the conidial adherence to and removal from the tick cuticle. As the concentration of conidia in the suspension increased, there were correlating increases in both the number of conidia adhering to engorged female R. annulatus and tick mortality. However, no correlation was observed between a tick's susceptibility to fungal infection and the amount of adhered conidia. These findings support the commonly accepted understanding of the nature of the adhesion process. The mechanism enabling the removal of the adhered conidia from the host cuticle is discussed. PMID- 20363786 TI - Toxicogenomic response of Rhodospirillum rubrum S1H to the micropollutant triclosan. AB - In the framework of the Micro-Ecological Life Support System Alternative (MELiSSA) project, a pilot study was performed to identify the effects of triclosan on the MELiSSA carbon-mineralizing microorganism Rhodospirillum rubrum S1H. Triclosan is a biocide that is commonly found in human excrement and is considered an emerging pollutant in wastewater and the environment. Chronic exposure to MELiSSA-relevant concentrations (> or =25 microg liter(-1)) of triclosan resulted in a significant extension of the lag phase of this organism but hardly affected the growth rate. Analytical determinations gave no indication of triclosan biodegradation during the growth experiment, and flow cytometric viability analyses revealed that triclosan is bacteriostatic and only slightly toxic to R. rubrum S1H. Using microarray analyses, the genetic mechanisms supporting the reversibility of triclosan-induced inhibition were scrutinized. An extremely triclosan-responsive cluster of four small adjacent genes was identified, for which there was up to 34-fold induction with 25 microg liter(-1) triclosan. These four genes, for which the designation microf (micropollutant upregulated factor) is proposed, appear to be unique to R. rubrum and are shown here for the first time to be involved in the response to stress. Moreover, numerous other systems that are associated with the proton motive force were shown to be responsive to triclosan, but they were never as highly upregulated as the microf genes. In response to triclosan, R. rubrum S1H induced transcription of the phage shock protein operon (pspABC), numerous efflux systems, cell envelope consolidation mechanisms, the oxidative stress response, beta-oxidation, and carbonic anhydrase, while there was downregulation of bacterial conjugation and carboxysome synthesis genes. The microf genes and three efflux-related genes showed the most potential to be low-dose biomarkers. PMID- 20363787 TI - Association of missense mutations in epoxyalkane coenzyme M transferase with adaptation of Mycobacterium sp. strain JS623 to growth on vinyl chloride. AB - Vinyl chloride (VC) is a toxic groundwater pollutant associated with plastic manufacture and chlorinated solvent use. Aerobic bacteria that grow on VC as a carbon and energy source can evolve in the laboratory from bacteria that grow on ethene, but the genetic changes involved are unknown. We investigated VC adaptation in two variants (JS623-E and JS623-T) of the ethene-oxidizing Mycobacterium strain JS623. Missense mutations in the EtnE gene developed at two positions (W243 and R257) in cultures exposed to VC but not in cultures maintained on ethene. Epoxyalkane-coenzyme M transferase (EaCoMT) activities in cell extracts of JS623-E and JS623-T (150 and 645 nmol/min/mg protein, respectively) were higher than that of wild-type JS623 (74 nmol/min/mg protein), and in both variant cultures epoxyethane no longer accumulated during growth on ethene. The heterologous expression of two variant etnE alleles (W243G [etnE1] and R257L [etnE2]) from strain JS623 in Mycobacterium smegmatis showed that they had 42 to 59% higher activities than the wild type. Recombinant JS623 cultures containing mutant EtnE genes cloned in the vector pMV261 adapted to growth on VC more rapidly than the wild-type JS623 strain, with incubation times of 60 days (wild type), 1 day (pMVetnE1), and 35 days (pMVetnE2). The JS623(pMVetnE) culture did not adapt to VC after more than 60 days of incubation. Adaptation to VC in strain JS623 is consistently associated with two particular missense mutations in the etnE gene that lead to higher EaCoMT activity. This is the first report to pinpoint a genetic change associated with the transition from cometabolic to growth-linked VC oxidation in bacteria. PMID- 20363788 TI - Effects of plant genotype and growth stage on the betaproteobacterial communities associated with different potato cultivars in two fields. AB - Bacterial communities in the rhizosphere are dynamic and susceptible to changes in plant conditions. Among the bacteria, the betaproteobacteria play key roles in nutrient cycling and plant growth promotion, and hence the dynamics of their community structures in the rhizosphere should be investigated. Here, the effects of plant cultivar, growth stage, and soil type on the communities associated with potato cultivars Aveka, Aventra, Karnico, Modena, Premiere, and Desiree were assessed for two different fields containing sandy soil with either a high or low organic compound content. Thus, bacterial and betaproteobacterial PCR-denaturing gradient gel electrophoresis analyses were performed to analyze the effects of plant cultivar and growth on the rhizosphere community structure. The analyses showed that in both fields all cultivars had a rhizosphere effect on the total bacterial and betaproteobacterial communities. In addition, the plant growth stage strongly affected the betaproteobacterial communities in both fields. Moreover, the community structures were affected by cultivar, and cultivars differed in physiology, as reflected in their growth rates, root development, and estimated tuber starch contents. Analyses of betaproteobacterial clone libraries constructed for two selected cultivars (one cultivar that produced low-starch content tubers and one cultivar that produced high-starch-content tubers), as well as bulk soil, revealed that the rhizospheres of the two cultivars selected for specific bacteria, including plant-growth-promoting bacteria, such as Variovorax and Achromobacter spp. In addition, quantitative PCR-based quantification of the Variovorax paradoxus-specific functional gene asfA (involved in desulfonation) indicated that there were clear potato rhizosphere effects on the abundance of this gene. Interestingly, both cultivar type and plant growth stage affected the community under some circumstances. PMID- 20363789 TI - Exploiting the natural diversity of microviridin gene clusters for discovery of novel tricyclic depsipeptides. AB - Microviridins are ribosomally synthesized tricyclic depsipeptides produced by different genera of cyanobacteria. The prevalence of the microviridin gene clusters and the natural diversity of microviridin precursor sequences are currently unknown. Screening of laboratory strains and field samples of the bloom forming freshwater cyanobacterium Microcystis via PCR revealed global occurrence of the microviridin pathway and an unexpected natural variety. We could detect 15 new variants of the precursor gene mdnA encoding microviridin backbones that differ in up to 4 amino acid positions from known isoforms of the peptide. The survey not only provides insights into the versatility of the biosynthetic enzymes in a closely related group of cyanobacteria, but also facilitates the discovery and characterization of cryptic microviridin variants. This is demonstrated for microviridin L in Microcystis aeruginosa strain NIES843 and heterologously produced variants. PMID- 20363790 TI - Fate of a Pseudomonas savastanoi pv. savastanoi type III secretion system mutant in olive plants (Olea europaea L.). AB - Pseudomonas savastanoi pv. savastanoi strain NCPPB 3335 is a model bacterial pathogen for studying the molecular basis of disease production in woody hosts. We report the sequencing of the hrpS-to-hrpZ region of NCPPB 3335, which has allowed us to determine the phylogenetic position of this pathogen with respect to previously sequenced Pseudomonas syringae hrp clusters. In addition, we constructed a mutant of NCPPB 3335, termed T3, which carries a deletion from the 3' end of the hrpS gene to the 5' end of the hrpZ operon. Despite its inability to multiply in olive tissues and to induce tumor formation in woody olive plants, P. savastanoi pv. savastanoi T3 can induce knot formation on young micropropagated olive plants. However, the necrosis and formation of internal open cavities previously reported in knots induced by the wild-type strain were not observed in those induced by P. savastanoi pv. savastanoi T3. Tagging of P. savastanoi pv. savastanoi T3 with green fluorescent protein (GFP) allowed real time monitoring of its behavior on olive plants. In olive plant tissues, the wild type strain formed aggregates that colonized the intercellular spaces and internal cavities of the hypertrophic knots, while the mutant T3 strain showed a disorganized distribution within the parenchyma of the knot. Ultrastructural analysis of knot sections revealed the release of extensive outer membrane vesicles from the bacterial cell surface of the P. savastanoi pv. savastanoi T3 mutant, while the wild-type strain exhibited very few vesicles. This phenomenon has not been described before for any other bacterial phytopathogen during host infection. PMID- 20363791 TI - Partial chromosome sequence of Spiroplasma citri reveals extensive viral invasion and important gene decay. AB - The assembly of 20,000 sequencing reads obtained from shotgun and chromosome specific libraries of the Spiroplasma citri genome yielded 77 chromosomal contigs totaling 1,674 kbp (92%) of the 1,820-kbp chromosome. The largest chromosomal contigs were positioned on the physical and genetic maps constructed from pulsed field gel electrophoresis and Southern blot hybridizations. Thirty-eight contigs were annotated, resulting in 1,908 predicted coding sequences (CDS) representing an overall coding density of only 74%. Cellular processes, cell metabolism, and structural-element CDS account for 29% of the coding capacity, CDS of external origin such as viruses and mobile elements account for 24% of the coding capacity, and CDS of unknown function account for 47% of the coding capacity. Among these, 21% of the CDS group into 63 paralog families. The organization of these paralogs into conserved blocks suggests that they represent potential mobile units. Phage-related sequences were particularly abundant and include plectrovirus SpV1 and SVGII3 and lambda-like SpV2 sequences. Sixty-nine copies of transposases belonging to four insertion sequence (IS) families (IS30, IS481, IS3, and ISNCY) were detected. Similarity analyses showed that 21% of chromosomal CDS were truncated compared to their bacterial orthologs. Transmembrane domains, including signal peptides, were predicted for 599 CDS, of which 58 were putative lipoproteins. S. citri has a Sec-dependent protein export pathway. Eighty-four CDS were assigned to transport, such as phosphoenolpyruvate phosphotransferase systems (PTS), the ATP binding cassette (ABC), and other transporters. Besides glycolytic and ATP synthesis pathways, it is noteworthy that S. citri possesses a nearly complete pathway for the biosynthesis of a terpenoid. PMID- 20363792 TI - Shuttle vector-based transformation system for Pyrococcus furiosus. AB - Pyrococcus furiosus is a model organism for analyses of molecular biology and biochemistry of archaea, but so far no useful genetic tools for this species have been described. We report here a genetic transformation system for P. furiosus based on the shuttle vector system pYS2 from Pyrococcus abyssi. In the redesigned vector, the pyrE gene from Sulfolobus was replaced as a selectable marker by the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (HMG-CoA) conferring resistance of transformants to the antibiotic simvastatin. Use of this modified plasmid resulted in the overexpression of the HMG-CoA reductase in P. furiosus, allowing the selection of strains by growth in the presence of simvastatin. The modified shuttle vector replicated in P. furiosus, but the copy number was only one to two per chromosome. This system was used for overexpression of His(6) tagged subunit D of the RNA polymerase (RNAP) in Pyrococcus cells. Functional RNAP was purified from transformed cells in two steps by Ni-NTA and gel filtration chromatography. Our data provide evidence that expression of transformed genes can be controlled from a regulated gluconeogenetic promoter. PMID- 20363793 TI - Engineering cyanobacteria to synthesize and export hydrophilic products. AB - Metabolic engineering of cyanobacteria has the advantage that sunlight and CO(2) are the sole source of energy and carbon for these organisms. However, as photoautotrophs, cyanobacteria generally lack transporters to move hydrophilic primary metabolites across membranes. To address whether cyanobacteria could be engineered to produce and secrete organic primary metabolites, Synechococcus elongatus PCC7942 was engineered to express genes encoding an invertase and a glucose facilitator, which mediated secretion of glucose and fructose. Similarly, expression of lactate dehydrogenase- and lactate transporter-encoding genes allowed lactate accumulation in the extracellular medium. Expression of the relevant transporter was essential for secretion. Production of these molecules was further improved by expression of additional heterologous enzymes. Sugars secreted by the engineered cyanobacteria could be used to support Escherichia coli growth in the absence of additional nutrient sources. These results indicate that cyanobacteria can be engineered to produce and secrete high-value hydrophilic products. PMID- 20363795 TI - Inhibitory effect of biocides on the viable masses and matrices of Staphylococcus aureus and Pseudomonas aeruginosa biofilms. AB - Bacteria and matrix are essential for the development of biofilms, and assays should therefore target both components. The current European guidelines for biocidal efficacy testing are not adequate for sessile microorganisms; hence, alternative discriminatory test protocols should be used. The activities of a broad range of biocides on Staphylococcus aureus and Pseudomonas aeruginosa biofilms were evaluated using such in vitro assays. Nearly all selected biocides showed a significant decrease in S. aureus biofilm viability, with sodium hypochlorite and peracetic acid as the most active biocides. Only hydrogen peroxide and sodium hypochlorite showed some inhibitory effect on the matrix. Treatment of P. aeruginosa biofilms was roughly comparable to that of S. aureus biofilms. Peracetic acid was the most active on viable mass within 1 min of contact. Isopropanol ensured a greater than 99.999% reduction of P. aeruginosa viability after at least 30 min of contact. Comparable to results with S. aureus, sodium hypochlorite and hydrogen peroxide markedly reduced the P. aeruginosa matrix. This study clearly demonstrated that despite their aspecific mechanisms of action, most biocides were active only against biofilm bacteria, leaving the matrix undisturbed. Only hydrogen peroxide and sodium hypochlorite were active on both the biofilm matrix and the viable mass, making them the better antibiofilm agents. In addition, this study emphasizes the need for updated and standardized guidelines for biofilm susceptibility testing of biocides. PMID- 20363794 TI - Application of real-time PCR to estimate toxin production by the cyanobacterium Planktothrix sp. AB - Quantitative real-time PCR methods are increasingly being applied for the enumeration of toxic cyanobacteria in the environment. However, to justify the use of real-time PCR quantification as a monitoring tool, significant correlations between genotype abundance and actual toxin concentrations are required. In the present study, we aimed to explain the concentrations of three structural variants of the hepatotoxin microcystin (MC) produced by the filamentous cyanobacterium Planktothrix sp., [Asp, butyric acid (Dhb)] microcystin-RR (where RR means two arginines), [Asp, methyl-dehydro-alanine (Mdha)]-microcystin-RR, and [Asp, Dhb]-microcystin-homotyrosine-arginine (HtyR), by the abundance of the microcystin genotypes encoding their synthesis. Three genotypes of microcystin-producing cyanobacteria (denoted the Dhb, Mdha, and Hty genotypes) in 12 lakes of the Alps in Austria, Germany, and Switzerland from 2005 to 2007 were quantified by means of real-time PCR. Their absolute and relative abundances were related to the concentration of the microcystin structural variants in aliquots determined by high-performance liquid chromatography (HPLC). The total microcystin concentrations varied from 0 to 6.2 microg liter(-1) (mean +/- standard error [SE] of 0.6 +/- 0.1 microg liter(-1)) among the samples, in turn resulting in an average microcystin content in Planktothrix of 3.1 +/- 0.7 microg mm(-3) biovolume. Over a wide range of the population density (0.001 to 3.6 mm(3) liter(-1) Planktothrix biovolume), the Dhb genotype and [Asp, Dhb]-MC RR were most abundant, while the Hty genotype and MC-HtyR were found to be in the lowest proportion only. In general, there was a significant linear relationship between the abundance/proportion of specific microcystin genotypes and the concentration/proportion of the respective microcystin structural variants on a logarithmic scale. We conclude that estimating the abundance of specific microcystin genotypes by quantitative real-time PCR is useful for predicting the concentration of microcystin variants in water. PMID- 20363796 TI - Microbial links between sulfate reduction and metal retention in uranium- and heavy metal-contaminated soil. AB - Sulfate-reducing bacteria (SRB) can affect metal mobility either directly by reductive transformation of metal ions, e.g., uranium, into their insoluble forms or indirectly by formation of metal sulfides. This study evaluated in situ and biostimulated activity of SRB in groundwater-influenced soils from a creek bank contaminated with heavy metals and radionuclides within the former uranium mining district of Ronneburg, Germany. In situ activity of SRB, measured by the (35)SO(4)(2-) radiotracer method, was restricted to reduced soil horizons with rates of < or =142 +/- 20 nmol cm(-3) day(-1). Concentrations of heavy metals were enriched in the solid phase of the reduced horizons, whereas pore water concentrations were low. X-ray absorption near-edge structure (XANES) measurements demonstrated that approximately 80% of uranium was present as reduced uranium but appeared to occur as a sorbed complex. Soil-based dsrAB clone libraries were dominated by sequences affiliated with members of the Desulfobacterales but also the Desulfovibrionales, Syntrophobacteraceae, and Clostridiales. [(13)C]acetate- and [(13)C]lactate-biostimulated soil microcosms were dominated by sulfate and Fe(III) reduction. These processes were associated with enrichment of SRB and Geobacteraceae; enriched SRB were closely related to organisms detected in soils by using the dsrAB marker. Concentrations of soluble nickel, cobalt, and occasionally zinc declined < or =100% during anoxic soil incubations. In contrast to results in other studies, soluble uranium increased in carbon-amended treatments, reaching < or =1,407 nM in solution. Our results suggest that (i) ongoing sulfate reduction in contaminated soil resulted in in situ metal attenuation and (ii) the fate of uranium mobility is not predictable and may lead to downstream contamination of adjacent ecosystems. PMID- 20363797 TI - Bacterial capture by peptide-mimetic oligoacyllysine surfaces. AB - Most procedures for detecting pathogens in liquid media require an initial concentration step. However, poor recovery efficiencies of conventional methods, such as filtration, often lead to low sensitivity. Here, we describe a strategy for concentrating bacteria using their binding affinity for an oligoacyllysine (OAK), a novel peptide-mimetic antimicrobial compound. We show that the resin linked OAK (ROAK) efficiently captures a variety of pathogens in different media, upon brief incubation with ROAK beads or after continuous flow through a ROAK packed column. Using Escherichia coli expressing green fluorescent protein, we show that binding occurs rapidly during incubation and persists after filtration as visualized by confocal microscopy. The high binding affinity of bacteria was confirmed by surface plasmon resonance technology using an OAK-linked chip. ROAK bound bacteria remained viable and were readily identifiable by real-time PCR after ethanol elution. A single ROAK bead is estimated to capture about 3,000 bacterial cells in culture medium, in contaminated saline or tap water. ROAK beads can be regenerated for multiple uses after brief ethanol treatment. Collectively, the data support the notion that OAK-based coating of polymeric surfaces might represent a useful means for medium filtration as well as for concentration of bacteria. PMID- 20363798 TI - The case of botulinum toxin in milk: experimental data. AB - Botulinum neurotoxin (BoNT) is the most toxic substance known to man and the causative agent of botulism. Due to its high toxicity and the availability of the producing organism Clostridium botulinum, BoNT is regarded as a potential biological warfare agent. Because of the mild pasteurization process, as well as rapid product distribution and consumption, the milk supply chain has long been considered a potential target of a bioterrorist attack. Since, to our knowledge, no empirical data on the inactivation of BoNT in milk during pasteurization are available at this time, we investigated the activities of BoNT type A (BoNT/A) and BoNT/B, as well as their respective complexes, during a laboratory-scale pasteurization process. When we monitored milk alkaline phosphatase activity, which is an industry-accepted parameter of successfully completed pasteurization, our method proved comparable to the industrial process. After heating raw milk spiked with a set amount of BoNT/A or BoNT/B or one of their respective complexes, the structural integrity of the toxin was determined by enzyme-linked immunosorbent assay (ELISA) and its functional activity by mouse bioassay. We demonstrated that standard pasteurization at 72 degrees C for 15 s inactivates at least 99.99% of BoNT/A and BoNT/B and at least 99.5% of their respective complexes. Our results suggest that if BoNTs or their complexes were deliberately released into the milk supply chain, standard pasteurization conditions would reduce their activity much more dramatically than originally anticipated and thus lower the threat level of the widely discussed "BoNT in milk" scenario. PMID- 20363799 TI - Antibiofilm activity of the marine bacterium Pseudoalteromonas sp. strain 3J6. AB - Biofilm formation results in medical threats or economic losses and is therefore a major concern in a variety of domains. In two-species biofilms of marine bacteria grown under dynamic conditions, Pseudoalteromonas sp. strain 3J6 formed mixed biofilms with Bacillus sp. strain 4J6 but was largely predominant over Paracoccus sp. strain 4M6 and Vibrio sp. strain D01. The supernatant of Pseudoalteromonas sp. 3J6 liquid culture (SN(3J6)) was devoid of antibacterial activity against free-living Paracoccus sp. 4M6 and Vibrio sp. D01 cells, but it impaired their ability to grow as single-species biofilms and led to higher percentages of nonviable cells in 48-h biofilms. Antibiofilm molecules of SN(3J6) were able to coat the glass surfaces used to grow biofilms and reduced bacterial attachment about 2-fold, which might partly explain the biofilm formation defect but not the loss of cell viability. SN(3J6) had a wide spectrum of activity since it affected all Gram-negative marine strains tested except other Pseudoalteromonas strains. Biofilm biovolumes of the sensitive strains were reduced 3- to 530-fold, and the percentages of nonviable cells were increased 3- to 225-fold. Interestingly, SN(3J6) also impaired biofilm formation by three strains belonging to the human-pathogenic species Pseudomonas aeruginosa, Salmonella enterica, and Escherichia coli. Such an antibiofilm activity is original and opens up a variety of applications for Pseudoalteromonas sp. 3J6 and/or its active exoproducts in biofilm prevention strategies. PMID- 20363800 TI - Carbohydrate metabolism in mutants of the cyanobacterium Synechococcus elongatus PCC 7942 defective in glycogen synthesis. AB - ADP-glucose pyrophosphorylase (AGPase) and glycogen synthase (GS) catalyze the first two reactions of glycogen synthesis in cyanobacteria. Mutants defective in each of these enzymes in Synechococcus elongatus PCC 7942 were constructed and characterized. Activities of the corresponding enzymes in the selected mutants were virtually undetectable, and their ability to synthesize glycogen was entirely abolished. The maximal activities of photosynthetic O(2) evolution and the rates of respiration in the dark were significantly decreased in the mutants compared to those in wild-type cells. Addition of 0.2 M NaCl or 3 mM H(2)O(2) to liquid cultures markedly inhibited the growth of the AGPase and GS mutants, while the same treatment had only marginal effects on the wild type. These results suggest a significant role for storage polysaccharides in tolerance to salt or oxidative stress. PMID- 20363801 TI - Nonmagnetotactic multicellular prokaryotes from low-saline, nonmarine aquatic environments and their unusual negative phototactic behavior. AB - Magnetotactic multicellular prokaryotes (MMPs) are unique magnetotactic bacteria of the Deltaproteobacteria class and the first found to biomineralize the magnetic mineral greigite (Fe(3)S(4)). Thus far they have been reported only from marine habitats. We questioned whether MMPs exist in low-saline, nonmarine environments. MMPs were observed in samples from shallow springs in the Great Boiling Springs geothermal field and Pyramid Lake, both located in northwestern Nevada. The temperature at all sites was ambient, and salinities ranged from 5 to 11 ppt. These MMPs were not magnetotactic and did not contain magnetosomes (called nMMPs here). nMMPs ranged from 7 to 11 microm in diameter, were composed of about 40 to 60 Gram-negative cells, and were motile by numerous flagella that covered each cell on one side, characteristics similar to those of MMPs. 16S rRNA gene sequences of nMMPs show that they form a separate phylogenetic branch within the MMP group in the Deltaproteobacteria class, probably representing a single species. nMMPs exhibited a negative phototactic behavior to white light and to wavelengths of < or =480 nm (blue). We devised a "light racetrack" to exploit this behavior, which was used to photoconcentrate nMMPs for specific purposes (e.g., DNA extraction) even though their numbers were low in the sample. Our results show that the unique morphology of the MMP is not restricted to marine and magnetotactic prokaryotes. Discovery of nonmagnetotactic forms of the MMP might support the hypothesis that acquisition of the magnetosome genes involves horizontal gene transfer. To our knowledge, this is the first report of phototaxis in bacteria of the Deltaproteobacteria class. PMID- 20363802 TI - Role of extracellular DNA in initial bacterial adhesion and surface aggregation. AB - Extracellular DNA (eDNA) is an important component of the biofilm matrix. We show that removal of eDNA from Gram-positive bacteria reduces initial adhesion to and aggregation of bacteria on surfaces. Thermodynamic analyses indicated that eDNA introduces favorable acid-base interactions, explaining the effect of eDNA on aggregation and adhesion to the surface. PMID- 20363803 TI - Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. AB - Seven-transmembrane receptors (7TMRs) signal through the well described heterotrimeric G proteins but can also activate G protein-independent signaling pathways of which the impact and complexity are less understood. The angiotensin II type 1 receptor (AT(1)R) is a prototypical 7TMR and an important drug target in cardiovascular diseases. "Biased agonists" with intrinsic "functional selectivity" that simultaneously blocks Galpha(q) protein activity and activates G protein-independent pathways of the AT(1)R confer important perspectives in treatment of cardiovascular diseases. In this study, we performed a global quantitative phosphoproteomics analysis of the AT(1)R signaling network. We analyzed ligand-stimulated SILAC (stable isotope labeling by amino acids in cell culture) cells by high resolution (LTQ-Orbitrap) MS and compared the phosphoproteomes of the AT(1)R agonist angiotensin II and the biased agonist [Sar(1),Ile(4),Ile(8)]angiotensin II (SII angiotensin II), which only activates the Galpha(q) protein-independent signaling. We quantified more than 10,000 phosphorylation sites of which 1183 were regulated by angiotensin II or its analogue SII angiotensin II. 36% of the AT(1)R-regulated phosphorylations were regulated by SII angiotensin II. Analysis of phosphorylation site patterns showed a striking distinction between protein kinases activated by Galpha(q) protein dependent and -independent mechanisms, and we now place protein kinase D as a key protein involved in both Galpha(q)-dependent and -independent AT(1)R signaling. This study provides substantial novel insight into angiotensin II signal transduction and is the first study dissecting the differences between a full agonist and a biased agonist from a 7TMR on a systems-wide scale. Importantly, it reveals a previously unappreciated diversity and quantity of Galpha(q) protein independent signaling and uncovers novel signaling pathways. We foresee that the amount and diversity of G protein-independent signaling may be more pronounced than previously recognized for other 7TMRs as well. Quantitative mass spectrometry is a promising tool for evaluation of the signaling properties of biased agonists to other receptors in the future. PMID- 20363804 TI - High chloroquine treatment failure rates and predominance of mutant genotypes associated with chloroquine and antifolate resistance among falciparum malaria patients from the island of Car Nicobar, India. AB - OBJECTIVES: An in vivo chloroquine efficacy study was undertaken on the island of Car Nicobar because a temporal rise in the Plasmodium falciparum parasite population containing mutations in the chloroquine resistance transporter (PfCRT) protein has been reported there. METHODS: A WHO protocol with a 28 day follow-up schedule was used for chloroquine efficacy studies. Finger-prick blood from P. falciparum malaria patients was used for sequencing the genes encoding PfCRT (exon 2), dihydrofolate reductase (PfDHFR) and dihydropteroate synthetase (PfDHPS). RESULTS: The majority of patients showed chloroquine treatment failure (60.42%, n=48). A higher early treatment failure (ETF) rate was recorded among non-responders (23 of 29, 79.31%). Each patient, irrespective of their chloroquine response, was infected with P. falciparum that contained mutated PfCRT (predominantly genotype C72V73I74E75T76) associated with high chloroquine resistance and none with the wild-type pfcrt gene. Therefore, mutated PfCRT was also present in the P. falciparum isolates of all the chloroquine responders. The majority of individuals from both groups also contained parasites with a high number of two-locus PfDHFR-PfDHPS mutations, associated with a high level of antifolate resistance. CONCLUSIONS: There is a predominance of chloroquine- and antifolate-resistant P. falciparum malaria in Car Nicobar, requiring an alternative antimalarial drug treatment policy, such as implementation of artesunate combination therapy (ACT), for this island. PMID- 20363806 TI - Effect of generics on price and consumption of ciprofloxacin in primary healthcare: the relationship to increasing resistance. AB - BACKGROUND: The introduction of generic versions of drugs has often resulted in an increase in the consumption of the agents involved. In December 2001, generic ciprofloxacin was marketed in Denmark. Our objective was to evaluate, in a community setting, the effect of price on consumption of ciprofloxacin and on ciprofloxacin resistance in Escherichia coli urine isolates. METHODS: We conducted a retrospective ecological study collecting monthly national data on the number of marketed versions and primary healthcare (PHC) sales of ciprofloxacin during January 1995-December 2005. Data were compared with a median price per defined daily dose (DDD) of ciprofloxacin during September 1999 December 2005. Yearly PHC consumption data from seven Danish counties were compared with the antimicrobial resistance profiles of PHC E. coli urine isolates. RESULTS: During 2002, the number of marketed versions increased from 3 to 10, and the median price per DDD decreased by 53%. From 2002 to 2005, the total consumption of oral ciprofloxacin in PHC increased significantly from 0.13 DDD/1000 inhabitant-days to 0.33 DDD/1000 inhabitant-days. During the same period, the frequency of ciprofloxacin resistance increased by 200%. A statistically significant correlation was found between the consumption of ciprofloxacin and the ciprofloxacin resistance rate in E. coli urine isolates, independent of the introduction of generic ciprofloxacin. CONCLUSIONS: After the introduction of generic ciprofloxacin, a significant increase in the total consumption of oral ciprofloxacin in PHC was observed in Denmark. The increase in consumption was significantly correlated with ciprofloxacin resistance in E. coli obtained from urine isolates. PMID- 20363805 TI - A potential role for daptomycin in enterococcal infections: what is the evidence? AB - Nosocomial infections caused by enterococci present a challenge for clinicians because treatment options are often limited due to the widespread occurrence of strains resistant to multiple antibiotics, including vancomycin. Daptomycin is a first-in-class cyclic lipopeptide that has proven efficacy for the treatment of Gram-positive infections. Although methicillin-resistant Staphylococcus aureus has been the most prominent target in the clinical development of daptomycin, this agent has demonstrated potent bactericidal activity in enterococcal infection models and has been used for the treatment of enterococcal infections in humans. In recent years, large-scale susceptibility studies have shown that daptomycin is active against >98% of enterococci tested, irrespective of their susceptibility to other antibacterial agents. This lack of cross-resistance reflects the fact that daptomycin has a mode of action distinct from those of other antibiotics, including glycopeptides. While there are limited data available from randomized controlled trials, extensive clinical experience with daptomycin in enterococcal infections (including bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and urinary tract infections) has been reported. This growing body of evidence provides useful insights regarding the efficacy of daptomycin against enterococci in clinical settings. PMID- 20363807 TI - Rhus verniciflua Stokes extract as a potential option for treatment of metastatic renal cell carcinoma: report of two cases. PMID- 20363808 TI - What goes down must come up: role of the posteromedial cortices in encoding and retrieval. AB - The hypothesis that the neural network supporting successful episodic memory retrieval overlaps with the regions involved in episodic encoding has garnered much interest; however, the role of the posteromedial regions remains to be fully elucidated. Functional magnetic resonance imaging (fMRI) studies during successful encoding typically demonstrate deactivation of posteromedial cortices, whereas successful retrieval of previously encoded information has been associated with activation of these regions. Here, we performed an event-related fMRI experiment during an associative face-name encoding and retrieval task to investigate the topography and functional relationship of the brain regions involved in successful memory processes. A conjunction analysis of novel encoding and subsequent successful retrieval of names revealed an anatomical overlap in bilateral posteromedial cortices. In this region, a significant negative correlation was found: Greater deactivation during encoding was related to greater activation during successful retrieval. In contrast, the hippocampus and prefrontal cortex demonstrated positive activation during both encoding and retrieval. Our results provide further evidence that posteromedial regions constitute critical nodes in the large-scale cortical network subserving episodic memory. These results are discussed in relation to the default mode hypothesis, the involvement of posteromedial cortices in successful memory formation and retention, as well as potential implications for aging and neurodegenerative disease. PMID- 20363809 TI - A workplace intervention for sick-listed employees with distress: results of a randomised controlled trial. AB - OBJECTIVES: To evaluate the effectiveness of a participatory workplace intervention compared with usual care for sick-listed employees with distress, with regard to return to work (RTW) within the 12-month follow-up. METHODS: Employees with distress and sick-listed for 2-8 weeks were randomised to a workplace intervention (n=73) or to usual care (n=72). The participatory workplace intervention is a stepwise process involving the sick-listed employee and their supervisor, aimed at reducing obstacles for RTW by reaching consensus about an action plan for RTW. Outcome variables were lasting RTW, cumulative sickness absence and stress-related symptoms. RESULTS: Overall, an HR of 0.99 (95% CI 0.70 to 1.39) indicated no effect of the workplace intervention on lasting RTW. However, the workplace intervention significantly reduced the time until lasting RTW for employees who at baseline intended to return to work despite symptoms with an HR of 2.05 (95% CI 1.22 to 3.45). Employees who intended to return to work despite symptoms returned to work after 55 days in the workplace intervention group and 120 days in the usual care group. No such effect of the intervention was found for employees without baseline intentions to return to work despite symptoms (HR=0.78, 95% CI 0.47 to 1.28). CONCLUSIONS: No overall effect of the participatory workplace intervention on lasting RTW was found. The workplace intervention appeared effective on lasting RTW for employees who at baseline intended to return to work despite symptoms. For employees who showed no baseline intention to return to work, the intervention did not have any effect. Other approaches are needed for this subgroup. This trial has been registered at the Dutch National Trial Register ISRCTN92307123. PMID- 20363810 TI - Illustrating injury. PMID- 20363811 TI - Cost of spinal cord injuries caused by rollover automobile crashes. AB - OBJECTIVE: To determine the reduction in direct cost for treatment of spinal cord injuries (SCI) in belted occupants involved in rollover automobile crashes in the USA that would result if severe roof intrusion were eliminated. METHODS: Risk of SCI per rollover crash and by belted/unbelted status was calculated for roof intrusion magnitude categories using 1993-2006 National Automotive Sampling System Crashworthiness Data System (CDS) data. Direct costs of SCI based on neurological level and completeness of SCI were calculated using data from the National SCI Statistical Center. RESULTS: A reduction in rate of SCI for belted occupants with >15 cm roof intrusion to the rate seen for belted occupants with 8 15 cm roof intrusion would reduce the direct cost of SCI by approximately $97 million annually. CONCLUSION: There would be substantial cost savings solely by a reduction in one uncommon type of injury, SCI, if severe roof intrusion were eliminated. PMID- 20363812 TI - Backing collisions: a study of drivers' eye and backing behaviour using combined rear-view camera and sensor systems. AB - CONTEXT: Backing crash injures can be severe; approximately 200 of the 2,500 reported injuries of this type per year to children under the age of 15 years result in death. Technology for assisting drivers when backing has limited success in preventing backing crashes. OBJECTIVES: Two questions are addressed: Why is the reduction in backing crashes moderate when rear-view cameras are deployed? Could rear-view cameras augment sensor systems? DESIGN: 46 drivers (36 experimental, 10 control) completed 16 parking trials over 2 days (eight trials per day). Experimental participants were provided with a sensor camera system, controls were not. Three crash scenarios were introduced. SETTING: Parking facility at UMass Amherst, USA. SUBJECTS: 46 drivers (33 men, 13 women) average age 29 years, who were Massachusetts residents licensed within the USA for an average of 9.3 years. Interventions Vehicles equipped with a rear-view camera and sensor system-based parking aid. MAIN OUTCOME MEASURES: Subject's eye fixations while driving and researcher's observation of collision with objects during backing. RESULTS: Only 20% of drivers looked at the rear-view camera before backing, and 88% of those did not crash. Of those who did not look at the rear view camera before backing, 46% looked after the sensor warned the driver. CONCLUSIONS: This study indicates that drivers not only attend to an audible warning, but will look at a rear-view camera if available. Evidence suggests that when used appropriately, rear-view cameras can mitigate the occurrence of backing crashes, particularly when paired with an appropriate sensor system. PMID- 20363813 TI - An observational study of seatbelt use among vehicle occupants in Nigeria. AB - OBJECTIVE: The use of seatbelts reduces the likelihood of death and severe injuries to crash-involved vehicle occupants by 45-60%. Several countries, including Nigeria, have laws mandating the use of seatbelts but compliance is not universal. This study was conducted to determine rates of use of seatbelts among vehicle occupants in Ibadan municipality. DESIGN: An observational study was conducted. A selected petrol station in each of the five local government areas in Ibadan municipality was used as an observation site. Observations were documented by trained research staff between 08:30 and 18:00 hours over a 6-day period. RESULTS: 5757 occupants in 2870 vehicles were observed. Approximately 90% of drivers were men. Driver seatbelts were installed in approximately 90% of vehicles. Overall seatbelt use was 18.7; 31.7% among drivers and 10.3% and 0.4% among front and rear-seated adults, respectively. Only one child (0.7%) was restrained. Significantly more female drivers 47.3% used their seatbelts compared with men, 30.3% (p<0.001). An adult passenger was more likely to be restrained when riding with a female driver (p=0.007) and when the driver was restrained (p=0.000). CONCLUSIONS: The study showed that seatbelt use among vehicle occupants was low. Further research into reasons for the non-use of restraints needs to be conducted so that these can be incorporated into programmes aimed at improving seatbelt use. PMID- 20363814 TI - Effects of domestic violence policies, alcohol taxes and police staffing levels on intimate partner homicide in large US cities. AB - OBJECTIVE: To assess the relationships between intimate partner homicide (IPH) and public policies including police staffing levels in large US cities. DESIGN: The research uses a multiple time-series design to examine the effects of statutes aimed at restricting access to firearms for perpetrators of domestic violence, allowing or mandating arrest for violators of domestic violence restraining orders (DVROs), beer excise taxes, and police staffing levels on IPH in 46 of the largest US cities from 1979 to 2003. Both total IPH and IPH committed with a firearm are analysed. Generalised estimating equations using a Poisson distribution are used to regress IPH on the policies and potential confounders. RESULTS: State statutes restricting those under DVROs from accessing firearms, and laws allowing the warrantless arrest of DVRO violators are associated with reductions in total and firearm IPH. Police staffing levels are also negatively associated with IPH and firearm IPH. There was no evidence that other policies to restrict firearm access to domestic violence offenders or alcohol taxes had a significant impact on IPH. CONCLUSIONS: Reducing access to firearms for DVRO defendants, increasing police staffing levels and allowing the warrantless arrest of DVRO violators may reduce the city-level risk of IPH. Future research should evaluate factors that may mediate the effect of these laws and increased police staffing levels on IPH to determine whether there are opportunities to increase their protective effect. Further research is needed on firearm law implementation to determine why the other tested laws were not found effective. PMID- 20363815 TI - Physical and psychosocial risk factors for musculoskeletal disorders in New Zealand nurses, postal workers and office workers. AB - OBJECTIVE: To investigate the association of physical and psychosocial risk factors with musculoskeletal disorders (MSDs) in New Zealand nurses, postal workers and office workers. DESIGN: A cross-sectional postal survey asking about demographic, physical and psychosocial factors and MSDs. PARTICIPANTS: A total of 911 participants was randomly selected; nurses from the Nursing Council of New Zealand database (n=280), postal workers from their employer's database (n=280) and office workers from the 2005 electoral roll (n=351). OUTCOME MEASURES: Self reported pain in the low back, neck, shoulder, elbow, wrist/hand or knee lasting more than 1 day in the month before the survey. RESULTS: The response rate was 58%, 443 from 770 potential participants. 70% (n=310) reported at least one MSDs. Physical work tasks were associated with low back (odds ratio (OR) 1.35, 95% CI 1.14 to 1.6), shoulder (OR 1.41, 95% CI 1.17 to 1.69), elbow (OR 1.14, 95% CI 1.13 to 1.83) and wrist/hand pain (OR 1.39, 95% CI 1.15 to 1.69). Job strain had the strongest association with neck pain (OR 3.46, 95% CI 1.30 to 9.21) and wrist/hand pain. Somatisation was weakly associated with MSDs at most sites. Better general and mental health status were weakly associated with lower odds of MSDs. CONCLUSIONS: In injury prevention and rehabilitation the physical nature of the work needs to be addressed for most MSDs, with modest decreases in risk seemingly possible. Addressing job strain could provide significant benefit for those with neck and wrist/hand pain, while the effects of somatisation and the promotion of good mental health may provide smaller but global benefits. PMID- 20363816 TI - Real-world performance of vehicle crash test: the case of EuroNCAP. AB - OBJECTIVE: To investigate whether the occupants in vehicles with better safety ratings according to EuroNCAP sustain fewer fatal and severe injuries than occupants in vehicles with worse experimental safety ratings when in frontal crashes. DESIGN: Case-control study. SETTING: A representative sample of crashes in Britain from 1996 to 2008 as gathered in the Cooperative Crash Injury Study (CCIS) database under the auspices of the UK Department of Transportation and augmented with EuroNCAP experimental ratings for each crashed vehicle. SUBJECTS: Drivers and front seat passengers while occupants of vehicles for which EuroNCAP test results were available and who met inclusion criteria meant to select those in crashes similar to those in the frontal experimental setting. MAIN OUTCOME MEASURES: Fatality and severe MAIS3+ injuries to the head, thorax, pelvis and lower extremities. RESULTS: The multivariate Poisson regression models on the 1259 cases who sustained crash conditions most similar to the experimental ones showed no statistically significant effect on either mortality or MAIS3+ injury in real-world crashes when travelling in cars with better safety ratings. For example, when compared to a driver in a vehicle rated as safest for head injuries MAIS3+ in frontal crashes, drivers in vehicles rated yellow or orange presented adjusted ORs of 0.6 (0.2 to 1.7) and 0.8 (0.3 to 2.1), respectively. CONCLUSIONS: No statistically significant relationships between the EuroNCAP safety scores and real-world death or severe injury outcomes were found, suggesting the need to review biomechanical criteria chosen to set cut-off points for the rating system. PMID- 20363817 TI - A practical approach for applying best practices in behavioural interventions to injury prevention. AB - Behavioural science when combined with engineering, epidemiology and other disciplines creates a full picture of the often fragmented injury puzzle and informs comprehensive solutions. To assist efforts to include behavioural science in injury prevention strategies, this paper presents a methodological tutorial that aims to introduce best practices in behavioural intervention development and testing to injury professionals new to behavioural science. This tutorial attempts to bridge research to practice through the presentation of a practical, systematic, six-step approach that borrows from established frameworks in health promotion and disease prevention. Central to the approach is the creation of a programme theory that links a theoretically grounded, empirically tested behaviour change model to intervention components and their evaluation. Serving as a compass, a programme theory allows for systematic focusing of resources on the likely most potent behavioural intervention components and directs evaluation of intervention impact and implementation. For illustration, the six-step approach is applied to the creation of a new peer-to-peer campaign, Ride Like a Friend/Drive Like You Care, to promote safe teen driver and passenger behaviours. PMID- 20363818 TI - Risk factors for injury and severe injury in youth ice hockey: a systematic review of the literature. AB - OBJECTIVE: To identify risk factors for injury in youth ice hockey (ie, body checking, age, player position, player experience and level of play). STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of the literature, including a meta-analysis component was completed. Ten electronic databases and the American Society for Testing and Materials Safety in Ice Hockey series (volumes 1-4) were systematically searched with strict inclusion and exclusion criteria to identify articles examining risk factors for injury in youth ice hockey. RESULTS: Participation in games, compared with practices, was associated with an increased risk of injury in all studies examined. Age, level of play and player position produced inconsistent findings. Body checking was identified as a significant risk factor for all injuries (summary rate ratio: 2.45; 95% CI 1.7 to 3.6) and concussion (summary odds ratio: 1.71; 95% CI 1.2 to 2.44). CONCLUSIONS: Findings regarding most risk factors for injury remain inconclusive; however, body checking was found to be associated with an increased risk of injury. Policy implications regarding delaying body checking to older age groups and to only the most elite levels requires further rigorous investigation. PMID- 20363819 TI - Evaluation of skiing and snowboarding injuries sustained in terrain parks versus traditional slopes. AB - This study compares skiing and snowboarding injuries in terrain parks versus slopes at two ski areas, 2000-05. A total of 3953 (26.7%) injuries occurred in terrain parks, predominantly among young male snowboarders. Terrain park injuries were more likely to be severe, involving head (RR 1.31, 95% CI 1.16 to 1.48) or back (RR 1.96, 95% CI 1.67 to 2.29). PMID- 20363820 TI - The modern paediatric injury pyramid: injuries in Massachusetts children and adolescents. AB - The objective of this study was to develop a modern version of the paediatric injury pyramid, a visual classification of injury severity, and to present mechanism-based pyramids. As the original paediatric injury pyramid was described in 1980, the injury epidemiology from 1980 was compared with 2004. Comprehensive emergency department, hospital discharge and death data for Massachusetts in 2004 were used to determine injury rates for residents aged 0-19 years. Injury pyramids were constructed on the basis of the number of injuries resulting in death, hospitalisations and emergency department visits. In 2004, unintentional and intentional injuries accounted for 197 deaths, 7120 hospitalisations and 199,814 emergency department visits giving a ratio of 1:36:1014. The 2004 injury pyramids differed by mechanism and intent. Compared with 1980, there were lower rates for overall injury and for most major injury mechanisms in Massachusetts in 2004. PMID- 20363821 TI - Towards evidence-informed sports safety policy for New South Wales, Australia: assessing the readiness of the sector. PMID- 20363822 TI - The design and use of cluster randomised controlled trials in evaluating injury prevention interventions: part 2. Design effect, sample size calculations and methods for analysis. PMID- 20363823 TI - Prevention of falls and fall related injuries in older people in nursing homes and hospitals. PMID- 20363824 TI - The translation imperative: moving research into policy. PMID- 20363825 TI - WHO launches TEACH-VIP E-Learning. PMID- 20363827 TI - Associations between schools' tobacco restrictions and adolescents' use of tobacco. AB - Schools are an important arena for smoking prevention. In many countries, smoking rates have been reduced among adolescents, but the use of smokeless tobacco is on the rise in some of these countries. We aimed to study the associations between schools' restrictions on smoking and snus and on the use of these tobacco products among students in upper secondary school. We employed data from a national representative study of 1444 Norwegian students, aged 16-20 years. Respondents were asked about their schools' restrictions on snus and smoking and own use of these products. We examined associations between restrictions and the use, controlling for age, gender, type of school and regional differences. We found clear consistent associations between schools' restrictions on tobacco use and less use of these products. More explicit pervasive restrictions were strongly associated with the prevalence of use. This first study on the associations between schools' restrictions on snus and the prevalence of snus use corroborate what has been found in many studies on smoking restrictions and smoking. Strict school tobacco policies may be an important tool if health authorities are interested in implementing measures to limit or reduce snus use among adolescents. PMID- 20363828 TI - Using time-structured data to estimate evolutionary rates of double-stranded DNA viruses. AB - Double-stranded (ds) DNA viruses are often described as evolving through long term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution. However, the hypothesis of codivergence between dsDNA viruses and their hosts has rarely been rigorously tested, even though the vast majority of nucleotide substitution rate estimates for dsDNA viruses are based upon this assumption. It is therefore important to estimate the evolutionary rates of dsDNA viruses independent of the assumption of host-virus codivergence. Here, we explore the use of temporally structured sequence data within a Bayesian framework to estimate the evolutionary rates for seven human dsDNA viruses, including variola virus (VARV) (the causative agent of smallpox) and herpes simplex virus-1. Our analyses reveal that although the VARV genome is likely to evolve at a rate of approximately 1 x 10(-5) substitutions/site/year and hence approaching that of many RNA viruses, the evolutionary rates of many other dsDNA viruses remain problematic to estimate. Synthetic data sets were constructed to inform our interpretation of the substitution rates estimated for these dsDNA viruses and the analysis of these demonstrated that given a sequence data set of appropriate length and sampling depth, it is possible to use time-structured analyses to estimate the substitution rates of many dsDNA viruses independently from the assumption of host-virus codivergence. Finally, the discovery that some dsDNA viruses may evolve at rates approaching those of RNA viruses has important implications for our understanding of the long-term evolutionary history and emergence potential of this major group of viruses. PMID- 20363829 TI - Differential regulation of mitogen-activated protein kinase pathways by acetaminophen and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide in TAMH cells. AB - Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States. 3'-Hydroxyacetanilide (AMAP), a regioisomer of APAP, is useful as a comparative tool for studying APAP-induced toxicity because it is nontoxic relative to APAP. Transforming growth factor-alpha transgenic mouse hepatocytes were treated with both isomers to investigate mitogen-activated protein kinase (MAPK) cascades in order to differentiate their toxicological outcomes. Posttranslational modifications of MAPK signaling were assessed using immunoblotting and Bioplex technology, whereas gene expression changes were measured using Affymetrix Mouse Gene 1.0 ST arrays. APAP treatment led to higher levels of glutathione depletion at 6 and 24 h compared with AMAP in mitochondria. Glutathione depletion was preceded by increased levels of c-Jun N terminal kinase (JNK) phosphorylation at 2 and 6 h after APAP treatment compared with AMAP, whereas AMAP treatment led to increased extracellular signal-regulated protein kinase (ERK) phosphorylation at 2 and 6 h compared with APAP. Furthermore, APAP treatment significantly upregulated jun oncogene (c-Jun) gene expression, which was confirmed by Western blotting for both the phosphorylated and the nonphosphorylated forms of c-Jun protein. Transfection with JNK siRNA attenuated APAP toxicity after 24 h, suggesting that higher levels of APAP induced activation of JNK were related to higher rates of cell death. In summary, genomic regulation of MAPK-related transcription factors coupled with posttranslational activation of their upstream kinases is critical in differentiating the toxicities of APAP and AMAP. PMID- 20363830 TI - Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative. AB - Transparency and documentation of the decision process are at the core of a credible risk assessment and, in addition, are essential in the presentation of a weight of evidence (WoE)-based approach. Lack of confidence in the risk assessment process (as the basis for a risk management decision), beginning with evaluation of raw data and continuing through the risk decision process, is largely because of issues surrounding transparency. There is a critical need to implement greater transparency throughout the risk assessment process, and although doing so will not guarantee the correctness of the risk assessment or that all risk assessors come up with the same conclusions, it will provide essential information on how a particular conclusion or decision was made, thereby increasing confidence in the conclusions. Recognizing this issue, the International Life Sciences Institute Health and Environmental Sciences Institute convened a multisector committee tasked with discussing this issue and examining existing guidance and recommendations related to transparency in risk assessment. The committee concluded that transparency is inextricably linked to credibility: credibility of the data, credibility of the risk assessment process, and credibility of the resulting decision making. To increase this credibility, existing guidance concerning criteria elements of transparency related to the risk assessment process must be more widely disseminated and applied, and raw data for studies used in human health and environmental risk assessment must be more widely available. Finally, the decision-making process in risk management must be better documented and a guidance framework established for both the process itself and its communication to the public. PMID- 20363831 TI - Long-term consequences of fetal and neonatal nicotine exposure: a critical review. AB - Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy (NRT) has been developed as a pharmacotherapy for smoking cessation and is considered to be a safer alternative for women to smoking during pregnancy. The safety of NRT use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring, such as impaired fertility, type 2 diabetes, obesity, hypertension, neurobehavioral defects, and respiratory dysfunction. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health. PMID- 20363832 TI - Cadmium regulates the expression of the CFTR chloride channel in human airway epithelial cells. AB - Cadmium is a toxic heavy metal ranked seventh on the Priority List of Hazardous Substances. As a byproduct of smelters, cadmium is a prevalent environmental contaminant. It is also a major component of cigarette smoke, and its inhalation is associated with decreased pulmonary function, lung cancer, and chronic obstructive pulmonary disease. Ion channels, including the cystic fibrosis transmembrane conductance regulator (CFTR), play a central role in maintaining fluid homeostasis and lung functions. CFTR is mostly expressed in epithelial cells, and little is known about the effect of cadmium exposure on lung epithelial cell function. We show that exposure to cadmium decreases the expression of the CFTR protein and subsequent chloride transport in human airway epithelial cells in vitro. Impairment of CFTR protein expression was also observed in vivo in the lung of mice after intranasal instillation of cadmium. We established that the inhibitory effect of cadmium was not a nonspecific effect of heavy metals, as nickel had no effect on CFTR protein levels. Finally, we show that selected antioxidants, including alpha-tocopherol (vitamin E), but not N acetylcysteine, can prevent the cadmium-induced suppression of CFTR. In summary, we have identified cadmium as a regulator of the CFTR chloride channel present in lung epithelial cells. Future strategies to prevent the deleterious effect of cadmium on epithelial cells and lung functions may benefit from the finding that alpha-tocopherol protects CFTR expression and function. PMID- 20363833 TI - The impact of functional status on life expectancy in older persons. AB - BACKGROUND: Although life tables provide a basis for estimating remaining life by age, gender, and race, these tables do not consider clinical characteristics or functional status, which can lead to wide variations in remaining years. Inclusion of functional status may permit more precise prognostic estimates of life expectancy and proportion of time in various functional states. METHODS: We used longitudinal data from the Established Populations for Epidemiologic Studies of the Elderly to determine transition probabilities between three functional states (independent in activities of daily living [ADL] and mobility, dependent in mobility but independent in ADL, and dependent in ADL) and death. These were used to estimate total life expectancy and life expectancy in each functional state. RESULTS: In general, the largest proportion of remaining life expectancy was spent in the persons' baseline functional status category. Persons younger than 80 years with dependencies, however, spend substantial proportions of their remaining years in a better functional status category, and mobility-disabled 70 year-old persons spend the greatest part of their life expectancy in the independent functional state. Functional status has a dramatic impact on life expectancy. For example, 75-year-old men and women without limitations have life expectancies 5 years longer than those with ADL limitation and more than 1 year longer than those limited in mobility. The life expectancy of an ADL-disabled 75 year-old is similar to that of an 85-year-old independent person; thus, the impact of the disability approximates being 10 years older with much more of the remaining life spent disabled. CONCLUSIONS: Both ADL and mobility disability result in diminished survival and more of that survival period spent in disabled states. PMID- 20363834 TI - Metabolic switching of human myotubes is improved by n-3 fatty acids. AB - The aim of the present study was to examine whether pretreatment with different fatty acids, as well as the liver X receptor (LXR) agonist T0901317, could modify metabolic switching of human myotubes. The n-3 FA eicosapentaenoic acid (EPA) increased suppressibility, the ability of glucose to suppress FA oxidation. Substrate-regulated flexibility, the ability to increase FA oxidation when changing from a high glucose, low fatty acid condition ("fed") to a high fatty acid, low glucose ("fasted") condition, was increased by EPA and other n-3 FAs. Adaptability, the capacity to increase FA oxidation with increasing FA availability, was enhanced after pretreatment with EPA, linoleic acid (LA), and palmitic acid (PA). T0901317 counteracted the effect of EPA on suppressibility and adaptability, but it did not affect these parameters alone. EPA per se accumulated less, however, EPA, LA, oleic acid, and T0901317 treatment increased the number of lipid droplets (LD) in myotubes. LD volume and intensity, as well as mitochondrial mass, were independent of FA pretreatment. Microarray analysis showed that EPA regulated more genes than the other FAs and that specific pathways involved in carbohydrate metabolism were induced only by EPA. The present study suggests a favorable effect of n-3 FAs on skeletal muscle metabolic switching and glucose utilization. PMID- 20363835 TI - Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin deficient mice. AB - The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1( /-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency. PMID- 20363836 TI - Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers. AB - The conversion of lysophosphatidic acid (LPA) to phosphatidic acid is carried out by the microsomal enzymes 1-acylglycerol-3-phosphate-O-acyltransferases (AGPATs). These enzymes are specific for acylating LPA at the sn-2 (carbon 2) position on the glycerol backbone and are important, because they provide substrates for the synthesis of phospholipids and triglycerides. At least, mutations in one isoform, AGPAT2, cause near complete loss of adipose tissue in humans. We cloned a cDNA predicted to be an AGPAT isoform, AGPAT11. This cDNA has been recently identified also as lysophosphatidylcholine acyltransferase 2 (LPCAT2) and lyso platelet activating factor acetyltransferase. When AGPAT11/LPCAT2/lyso platelet-activating factor acetyltransferase cDNA was expressed in CHO and HeLa cells, the protein product localized to the endoplasmic reticulum. In vitro enzymatic activity using lysates of Human Embryonic Kidney-293 cells infected with recombinant AGPAT11/LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA adenovirus show that the protein has an AGPAT activity but lacks glycerol-3-phosphate acyltransferase enzymatic activity. The AGPAT11 efficiently uses C18:1 LPA as acyl acceptor and C18:1 fatty acid as an acyl donor. Thus, it has similar substrate specificities for LPA and acyl-CoA as shown for AGPAT9 and 10. Expression of AGPAT11 mRNA was significantly upregulated in human breast, cervical, and colorectal cancer tissues, indicating its adjuvant role in the progression of these cancers. Our enzymatic assays strongly suggest that the cDNA previously identified as LPCAT2/lyso platelet-activating factor-acetyltransferase cDNA has AGPAT activity and thus we prefer to identify this clone as AGPAT11 as well. PMID- 20363837 TI - Determinants of ICU care in the last month of life for Taiwanese cancer decedents, 2001 to 2006. AB - BACKGROUND: Use of the hospital ICU is rising rapidly for end-of-life care. The purpose of this population-based study was to determine the prevalence of ICU care in the last month of life of patients with cancer and the associations between ICU care and patient demographics, disease characteristics, physician specialty, hospital characteristics, and availability of health-care resources at the hospital and regional levels in Taiwan. METHODS: This retrospective cohort study used administrative data for 204,850 cancer decedents from 2001 to 2006. RESULTS: Rates of hospital ICU care in the last month of life did not change significantly from 2001 to 2006 (11.27%-12.71%). ICU use in the last month of life was more likely for single male patients aged < 65 years who had hematologic malignancies or esophageal cancer and more comorbidities or a nononcologist as primary-care physician. Patients with cancer were one-third less likely to use ICU care in their last month of life if they received care in a private hospital than if they were cared for in a public hospital. Patient propensity to receive ICU care in the last month of life was positively associated with increasing quartile of total hospital beds in their primary hospital's region. CONCLUSIONS: Slightly more than one-tenth of Taiwanese patients with cancer received ICU care in their last month of life. ICU use was strongly influenced by receiving care in hospitals and regions with abundant health-care resources. Resources should be devoted to ensure that ICU care at the end of life best meets patients' individual needs and interests. PMID- 20363838 TI - Clinical characteristics in two subgroups of obstructive sleep apnea syndrome in the elderly: comparison between cases with elderly and middle-age onset. AB - BACKGROUND: Morbidity due to obstructive sleep apnea syndrome (OSAS) is increased in the elderly population. However, the clinical characteristics of OSAS in elderly patients have not been characterized conclusively. The aim of this study was to clarify differences in clinical characteristics of OSAS between patients with middle-age onset and elderly onset of OSAS. METHODS: Patients with OSAS aged > or = 65 years were classified into groups according to age at first identification of respiratory pauses during sleep: a middle-age onset group (n = 32) where onset was at age < 50 years and an elderly onset group (n = 31) where onset was at age > or = 60 years. We compared demographic variables; polysomnographic variables; daytime sleepiness measures, including the multiple sleep latency test (MSLT) and the Epworth sleepiness scale (ESS); and adequate level of nasal continuous positive airway pressure (CPAP) between groups. RESULTS: BMI and frequency of underlying cardiovascular disorder were lower in the elderly onset group than in the middle-age onset group. No significant differences in apnea-hypopnea index or percentage of the period showing O(2) desaturation were seen between groups. However, arousal index, maximal negative esophageal pressure value, and adequate nasal CPAP level were significantly smaller in the elderly onset group. Mean sleep latency on MSLT was longer, and ESS score was lower in the elderly onset group. CONCLUSIONS: Compared with the middle-age onset group, the clinical significance of OSAS in the elderly onset group seemed to remain milder. This finding is possibly because of the smaller physiologic response to respiratory events. PMID- 20363839 TI - Effects of aerobic training on psychosocial morbidity and symptoms in patients with asthma: a randomized clinical trial. AB - BACKGROUND: Asthma symptoms reduce patients' daily activities, impair their health-related quality of life (HRQoL), and increase their reports of anxiety and depression, all of which seem to be related to a decrease in asthma control. Aerobic exercise training is known to improve aerobic fitness and reduce dyspnea in asthmatics; however, its effect in reducing psychologic distress and symptoms remains poorly understood. We evaluated the role of an aerobic training program in improving HRQoL (primary aim) and reducing psychologic distress and asthma symptoms (secondary aims) for patients with moderate or severe persistent asthma. METHODS: A total of 101 patients were randomly assigned to either a control group or an aerobic training group and studied during the period between medical consultations. Control group patients (educational program plus breathing exercises) (n = 51) and training group patients (educational program plus breathing exercises plus aerobic training) (n = 50) were followed twice a week during a 3-month period. HRQoL and levels of anxiety and depression were quantified before and after treatment. Asthma symptoms were evaluated monthly. RESULTS: At 3 months, the domains (physical limitations, frequency of symptoms, and psychosocial) and total scores of HRQoL significantly improved only in the training group patients (P < .001); the number of asthma-symptom-free days and anxiety and depression levels also significantly improved in this group (P < .001). In addition, a linear relationship between improvement in aerobic capacity and the days without asthma symptoms was observed (r = 0.47; P < .01). CONCLUSIONS: Our results suggest that aerobic training can play an important role in the clinical management of patients with persistent asthma. Further, they may be especially useful for patients with higher degrees of psychosocial distress. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT-00989365. PMID- 20363840 TI - Predictors of time to death after terminal withdrawal of mechanical ventilation in the ICU. AB - BACKGROUND: Little information exists about the expected time to death after terminal withdrawal of mechanical ventilation. We sought to determine the independent predictors of time to death after withdrawal of mechanical ventilation. METHODS: We conducted a secondary analysis from a cluster randomized trial of an end-of-life care intervention. We studied 1,505 adult patients in 14 hospitals in Washington State who died within or shortly after discharge from an ICU following terminal withdrawal of mechanical ventilation (August 2003 to February 2008). Time to death and its predictors were abstracted from the patients' charts and death certificates. Predictors included demographics, proxies of severity of illness, life-sustaining therapies, and International Classification of Diseases, 9th ed., Clinical Modification codes. RESULTS: The median (interquartile range [IQR]) age of the cohort was 71 years (58-80 years), and 44% were women. The median (IQR) time to death after withdrawal of ventilation was 0.93 hours (0.25-5.5 hours). Using Cox regression, the independent predictors of a shorter time to death were nonwhite race (hazard ratio [HR], 1.17; 95% CI, 1.01-1.35), number of organ failures (per-organ HR, 1.11; 95% CI, 1.04-1.19), vasopressors (HR, 1.67; 95% CI, 1.49-1.88), IV fluids (HR, 1.16; 95% CI, 1.01-1.32), and surgical vs medical service (HR, 1.29; 95% CI, 1.06-1.56). Predictors of longer time to death were older age (per-decade HR, 0.95; 95% CI, 0.90-0.99) and female sex (HR, 0.86; 95% CI, 0.77-0.97). CONCLUSIONS: Time to death after withdrawal of mechanical ventilation varies widely, yet the majority of patients die within 24 hours. Subsequent validation of these predictors may help to inform family counseling at the end of life. PMID- 20363841 TI - Do symptoms predict COPD in smokers? AB - BACKGROUND: The US Preventive Services Task Force recommends against spirometry in the absence of symptoms. However, as much as 50% of COPD cases in the United States remain undiagnosed. METHODS: Report of symptoms, smoking history, and spirometric data were collected from subjects screened for a work-related medical evaluation (N = 3,955). Prevalence of airflow obstruction and respiratory symptoms were assessed. Sensitivity, specificity, positive and negative predictive values, and relative risks of predicting symptoms and smoking history for COPD were calculated. RESULTS: Forty-four percent of smokers in our sample had airways obstruction (AO). Of these, 36% reported a diagnosis of or treatment for COPD. Odds ratio (95% CI) for AO with smoking (> or = 20 pack-years) was 3.73 (3.12- 4.45), 1.98 (1.73-2.27) for cough, 1.79 (1.55-2.08) for dyspnea, 1.95 (1.70-2.34) for sputum, and 2.59 (2.26-2.97) for wheeze. Respiratory symptoms were reported by 92% of smokers with AO, 86% smokers with restriction, 76% smokers with normal spirometry, and 73% of nonsmokers. Sensitivity (92% vs 90%), specificity (19% vs 22%), positive (47% vs 40%) and negative (75% vs 80%) predictive values for the presence of one or more symptoms were similar between smokers and all subjects. CONCLUSIONS: COPD is underdiagnosed in the United States. Symptoms are frequent in subjects with AO and increase their risk for COPD, but add little beyond age and smoking history to the predictive value of spirometry. In view of the high prevalence of symptoms and their poor predictive value, a simpler and more effective approach would be to screen older smokers. PMID- 20363842 TI - In vitro evaluation of endotracheal tubes with intrinsic suction. AB - BACKGROUND: Endotracheal tube (ETT) intubation impairs mucus clearance, which can lead to respiratory compromise. We compared three ETTs that have intrinsic capacity to aspirate secretions pooling above the cuff. METHODS: We evaluated the ability of three ETTs with suction, Hi-Lo Evac, Teleflex ISIS, and Portex Blue Line SACETT, to aspirate saliva and mucus simulants at continuous or intermittent vacuum pressures. We also evaluated the potential for a flexible tracheal membrane to obstruct the ETT suction port with applied vacuum. We measured the dimensions of the suction tubing at critical points to calculate differences in flow. RESULTS: In a rigid tracheal model, the ISIS aspirated saliva simulant more quickly with continuous low pressure suction than Evac (P = .0006) and SACETT (P < .0001) as well as with intermittent high pressure suction (P < .0001). For mucus simulant, the ISIS aspirated stimulant better than the other ETTs at high intermittent suction (P < .0001); the Evac was more effective than the SACETT (P = .0019). For low and continuous suction, suction ports in all ETTs occluded with mucus, except for ISIS, at the highest continuous suction tested. In a trachea model with a flexible posterior membrane, this membrane either partially or completely occluded the suction port of all tubes at high continuous or intermittent suction. The ISIS was more prone to obstruction by the flexible membrane than the Evac. We found large differences in suction tubing cross sectional area between the ISIS and the other tubes, and flow calculations using the Hagen-Poiseuille equation can explain the observed differences in volumes aspirated and tendency toward lumen obstruction. CONCLUSIONS: The ISIS transmits suction pressure to the tube orifice more powerfully than the Evac and SACETT. This feature makes the ISIS less prone to obstruction by mucus but more likely to obstruct by tissue suction. PMID- 20363843 TI - Bronchial challenges and respiratory symptoms in elite swimmers and winter sport athletes: Airway hyperresponsiveness in asthma: its measurement and clinical significance. AB - This study was aimed at the following: (1) the prevalence of airway hyperresponsiveness (AHR) and exercise-induced bronchoconstriction (EIB) in swimmers and winter sport athletes according to the previously recommended regulatory sport agencies criteria, (2) the relationship between respiratory symptoms and AHR/EIB, (3) the impact of the chosen cutoff value for AHR on its prevalence, and (4) the effect on the prevalence of the positive eucapnic voluntary hyperpnea (EVH) test of using the highest vs the lowest spirometric post-EVH values to calculate the magnitude of the airway response. We compared the prevalence of respiratory symptoms with responses to methacholine challenge and EVH in 45 swimmers, 45 winter sport athletes, and 30 controls. Two methacholine challenge cutoffs for AHR were analyzed: or= 2) dysfunctions increased from 11.7% in 1997 to 27.6% in 2006, the hospital mortality changed little, averaging 30.8%. Among survivors, 34.4% developed at least one subsequent severe sepsis episode, which contributed 30.2% to the disease burden in 10 years. CONCLUSIONS: The incidence and disease severity of severe sepsis in Taiwan are increasing. One-third of the survivors developed at least one subsequent episode, which contributed substantially to the disease burden over time. PMID- 20363845 TI - Respiratory viruses in adults with community-acquired pneumonia. AB - BACKGROUND: Use of nucleic acid amplification techniques has increased the identification of respiratory viruses (RVs) in adult patients with community acquired pneumonia (CAP). The objectives of the present study were to identify RV in patients with CAP using three different sampling methods and to compare CAP virus proportions and types with two comparison groups. METHODS: The study population included 183 adult patients with CAP, 450 control subjects, and 201 patients with nonpneumonic lower respiratory tract infection (NPLRTI). Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washing, and the samples were tested for detection of 12 RVs by multiplex TaqMan Hydrolysis probe-based real-time polymerase chain reaction (Integrated DNA Technology; Coralville, IA). RESULTS: At least one RV was identified in 58 patients with CAP (31.7%) compared with 32 (7.1%) in control subjects and 104 (51.7%) in patients with NPLRTI (P < .01 and P < .01, respectively). Coronaviruses were identified in 24 (13.1%) patients with CAP, compared with 17 (3.8%) in control subjects, and 21 (10.4%) patients with NPLRTI. Respiratory syncytial virus was identified in 13 (7.1%), four (0.9%), and seven (3.5%); rhinovirus in nine (4.9%), nine (2.0%), and 15 (7.5%); and influenza virus in eight (4.4%), two (0.4%), and 63 (31.3%) patients with CAP, control subjects, and patients with NPLRTI, respectively. CONCLUSIONS: The proportion of RV involvement in CAP is higher than previously reported. The proportion of RV identified in healthy subjects is significantly lower than in CAP, but it is not zero and should be weighed when interpreting corresponding proportions among patients. PMID- 20363846 TI - A multicenter, prospective, advanced diagnostic bronchoscopy outcomes registry. AB - BACKGROUND: Multiple new diagnostic bronchoscopic technologies are available, but little is known about their comparative performance and specific yield when adjusted for location of lesions, target size, and diagnosis. We present a multi institutional prospective-outcomes database to assess diagnostic yields of advanced bronchoscopic procedures, as well as related morbidity and mortality. METHODS: Data were extracted and reviewed from an ongoing, paper-based, prospective, multi-institutional outcomes database for advanced diagnostic bronchoscopic procedures. All consecutive eligible patients are entered into this database, and information on demographics, procedure, and lesion characteristics as well as complications were documented. Descriptive statistical analyses were performed. RESULTS: A total of 310 diagnostic procedures were performed over a 1 year period in four institutions by 15 different clinicians. The majority of the patients were white (66%), male (56%), former smokers (55%), with a mean age of 61 +/- 14 years. The average procedure time was 36 min, and the most common procedure was transbronchial needle aspiration (TBNA) (n = 198). Nodal tissue was obtained in 82.3% from TBNA sampling with a mean of three passes using endobronchial ultrasound guidance with a 22-gauge needle and mostly without on site cytology. The overall diagnostic yield for all procedures was 75%. There were few complications, and none required a change in disposition. CONCLUSIONS: Prospective and ongoing data analysis for bronchoscopic procedures is feasible and valuable. Lesion-adjusted diagnostic yields can be documented and potentially used for comparative assessment of different technologies and operators, as well as benchmarking and quality improvement initiatives. Extending the number of participating centers and web-based submission to minimize missing data components are the next, already-initiated steps. PMID- 20363847 TI - Continuous positive airway pressure effects on regional lung aeration in patients with COPD: a high-resolution CT scan study. AB - BACKGROUND: The effects of nasal continuous positive airway pressure (CPAP) on the lung parenchyma of patients with COPD, to our knowledge, have never been assessed by high-resolution CT (HRCT) scanning. METHODS: HRCT scans were obtained at the apex, hilum, and basis of the lungs at functional residual capacity while on spontaneous respiration and at the end of CPAP trials of 5 cm water (H(2)O), 10 cm H(2)O, and 15 cm H(2)O in 11 stable patients with COPD and eight healthy volunteers. Lung aeration was assessed by quantitative density parameters and by qualitative analysis of each CT image after processing by means of a density based color-mask computational algorithm. The quantitative parameters were density histograms, the relative area of the lungs with attenuation values < -950 Hounsfield units (percentage of hyperaerated areas) and the 15th percentile (the density value separating the 15% voxels of least density). RESULTS: A CPAP of 5 cm H(2)O caused little increase in lung aeration in both groups, but in some patients with COPD, CPAP deflated some regions of the lungs. CPAP levels of 10 cm H(2)O and 15 cm H(2)O increased the emphysematous zones in all sectors of the lungs, including dorsal and apical regions in patients with COPD compared to little hyperaeration predominantly in the ventral areas in healthy volunteers. CONCLUSIONS: Nasal CPAP causes variable effects on regional lung aeration in relation to the applied pressure and the regional distribution of emphysema in patients with COPD. Low pressure levels may cause regional lung deflation in some patients. High levels increase the emphysematous areas wherever they are located inside the lungs. PMID- 20363849 TI - Bronchial epithelial damage after a half-marathon in nonasthmatic amateur runners. AB - High neutrophil counts in induced sputum have been found in nonasthmatic amateur runners at rest and after a marathon, but the pathogenesis of airway neutrophilia in athletes is still poorly understood. Bronchial epithelial damage may occur during intense exercise, as suggested by investigations conducted in endurance trained mice and competitive human athletes studied under resting conditions. To gain further information on airway changes acutely induced by exercise, airway cell composition, apoptosis, IL-8 concentration in induced sputum, and serum CC 16 level were measured in 15 male amateur runners at rest (baseline) and shortly after a half-marathon. Different from results obtained after a marathon, neutrophil absolute counts were unchanged, whereas bronchial epithelial cell absolute counts and their apoptosis increased significantly (P < 0.01). IL-8 in induced sputum supernatants almost doubled postrace compared with baseline (P < 0.01) and correlated positively with bronchial epithelial cell absolute counts (R(2) = 0.373, P < 0.01). Serum CC-16 significantly increased after all races (P < 0.01). These data show mild bronchial epithelial cell injury acutely induced by intense endurance exercise in humans, extending to large airways the data obtained in peripheral airways of endurance-trained mice. Therefore, neutrophil influx into the airways of athletes may be secondary to bronchial epithelial damage associated with intense exercise. PMID- 20363848 TI - Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide. AB - Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2-4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000-1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction. PMID- 20363850 TI - Mesenchymal stem cells in chronic lung disease: culprit or savior? PMID- 20363852 TI - Type 7 adenylyl cyclase-mediated hypothalamic-pituitary-adrenal axis responsiveness: influence of ethanol and sex. AB - Although ethanol has been considered to be an anxiolytic agent, consumption of ethanol has also been shown to increase plasma adrenocorticotropin and glucocorticoids. The corticotrophin-releasing factor (CRF) receptor 1alpha (CRF R1) is a G protein-coupled receptor that activates adenylyl cyclase (AC), leading to adrenocorticotropin (and subsequently glucocorticoid) release into the circulation. There are nine members of the membrane-bound AC family, and the type 7 AC (AC7) is most sensitive to ethanol, which enhances the responsiveness of AC7 to G protein-coupled receptor activation. We determined the time course of ethanol's effect on plasma adrenocorticotropin and corticosterone levels in male and female AC7 transgenic (Adcy7(huTG)) mice (in which AC7 is overexpressed in neural tissue) and AC7 heterozygous knockdown [Adcy7(+/-)] mice (in which AC7 is underexpressed in neural tissue), and their respective littermate controls [wild type (WT)]. CRF-R1 mRNA and mRNA and protein for different forms of ACs were measured by using gene expression arrays, quantitative reverse transcription polymerase chain reaction, and immunoblotting in pituitaries of all animals. Our results demonstrated increased levels of AC7 in pituitary of Adcy7(huTG) mice and decreased levels in pituitary of Adcy7(+/-) mice compared with WT animals. Male and female Adcy7(huTG) mice displayed higher plasma adrenocorticotropin and corticosterone levels than WT and/or Adcy7(+/-) mice after ethanol injection. Female mice displayed higher adrenocorticotropin and corticosterone levels after ethanol injection than males, regardless of genotype. The data provide evidence for an integral role of AC7 in the increase of plasma adrenocorticotropin and corticosterone levels during alcohol intoxication. PMID- 20363853 TI - Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF 3084014. AB - PF-3084014 [(S)-2-((S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-3-ylamino)-N-(1 (2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide] is a novel gamma-secretase inhibitor that reduces amyloid-beta (Abeta) production with an in vitro IC(50) of 1.2 nM (whole-cell assay) to 6.2 nM (cell-free assay). This compound inhibits Notch-related T- and B-cell maturation in an in vitro thymocyte assay with an EC(50) of 2.1 microM. A single acute dose showed dose-dependent reduction in brain, cerebrospinal fluid (CSF), and plasma Abeta in Tg2576 mice as measured by enzyme-linked immunosorbent assay and immunoprecipitation (IP)/mass spectrometry (MS). Guinea pigs were dosed with PF-3084014 for 5 days via osmotic minipump at 0.03 to 3 mg/kg/day and exhibited dose-dependent reduction in brain, CSF, and plasma Abeta. To further characterize Abeta dynamics in brain, CSF, and plasma in relation to drug exposure and Notch-related toxicities, guinea pigs were dosed with 0.03 to 10 mg/kg PF-3084014, and tissues were collected at regular intervals from 0.75 to 30 h after dose. Brain, CSF, and plasma all exhibited dose-dependent reductions in Abeta, and the magnitude and duration of Abeta lowering exceeded those of the reductions in B-cell endpoints. Other gamma secretase inhibitors have shown high potency at elevating Abeta in the conditioned media of whole cells and the plasma of multiple animal models and humans. Such potentiation was not observed with PF-3084014. IP/MS analysis, however, revealed dose-dependent increases in Abeta11-40 and Abeta1-43 at doses that potently inhibited Abeta1-40 and Abeta1-42. PF-3084014, like previously described gamma-secretase inhibitors, preferentially reduced Abeta1-40 relative to Abeta1-42. Potency at Abeta relative to Notch-related endpoints in vitro and in vivo suggests that a therapeutic index can be achieved with this compound. PMID- 20363854 TI - Human recombinant vascular endothelial growth factor reduces necrosis and enhances hepatocyte regeneration in a mouse model of acetaminophen toxicity. AB - We reported previously that vascular endothelial growth factor (VEGF) was increased in acetaminophen (APAP) toxicity in mice and treatment with a VEGF receptor inhibitor reduced hepatocyte regeneration. The effect of human recombinant VEGF (hrVEGF) on APAP toxicity in the mouse was examined. In early toxicity studies, B6C3F1 mice received hrVEGF (50 microg s.c.) or vehicle 30 min before receiving APAP (200 mg/kg i.p.) and were sacrificed at 2, 4, and 8 h. Toxicity was comparable at 2 and 4 h, but reduced in the APAP/hrVEGF mice at 8 h (p < 0.05) compared with the APAP/vehicle mice. Hepatic glutathione (GSH) and APAP protein adduct levels were comparable between the two groups of mice, with the exception that GSH was higher at 8 h in the hrVEGF-treated mice. Subsequently, mice received two doses (before and 10 h) or three doses (before and 10 and 24 h) of hrVEGF; alanine aminotransferase values and necrosis were reduced at 24 and 36 h, respectively, in the APAP/hrVEGF mice (p < 0.05) compared with the APAP/vehicle mice. Proliferating cell nuclear antigen expression was enhanced, and interleukin-6 expression was reduced in the mice that received hrVEGF (p < 0.05) compared with the APAP/vehicle mice. In addition, treatment with hrVEGF lowered plasma hyaluronic acid levels and neutrophil counts at 36 h. Cumulatively, the data show that treatment with hrVEGF reduced toxicity and increased hepatocyte regeneration in APAP toxicity in the mouse. Attenuation of sinusoidal cell endothelial dysfunction and changes in neutrophil dynamics may be operant mechanisms in the hepatoprotection mediated by hrVEGF in APAP toxicity. PMID- 20363851 TI - Epithelial repair mechanisms in the lung. AB - The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF alpha, KGF, HGF), chemokines (MCP-1), interleukins (IL-1beta, IL-2, IL-4, IL-13), and prostaglandins (PGE(2)), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-beta and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes. PMID- 20363855 TI - PLANT HOMOLOGOUS TO PARAFIBROMIN is a component of the PAF1 complex and assists in regulating expression of genes within H3K27ME3-enriched chromatin. AB - The human Paf1 complex (Paf1C) subunit Parafibromin assists in mediating output from the Wingless/Int signaling pathway, and dysfunction of the encoding gene HRPT2 conditions specific cancer-related disease phenotypes. Here, we characterize the organismal and molecular roles of PLANT HOMOLOGOUS TO PARAFIBROMIN (PHP), the Arabidopsis (Arabidopsis thaliana) homolog of Parafibromin. PHP resides in an approximately 670-kD protein complex in nuclear extracts, and physically interacts with other known Paf1C-related proteins in vivo. In striking contrast to the developmental pleiotropy conferred by mutation in other plant Paf1C component genes in Arabidopsis, loss of PHP specifically conditioned accelerated phase transition from vegetative growth to flowering and resulted in misregulation of a very limited subset of genes that included the flowering repressor FLOWERING LOCUS C. Those genes targeted by PHP were distinguished from the bulk of Arabidopsis genes and other plant Paf1C targets by strong enrichment for trimethylation of lysine-27 on histone H3 (H3K27me3) within chromatin. These findings suggest that PHP is a component of a plant Paf1C protein in Arabidopsis, but has a more specialized role in modulating expression of a subset of Paf1C targets. PMID- 20363856 TI - A comprehensive toolkit of plant cell wall glycan-directed monoclonal antibodies. AB - A collection of 130 new plant cell wall glycan-directed monoclonal antibodies (mAbs) was generated with the aim of facilitating in-depth analysis of cell wall glycans. An enzyme-linked immunosorbent assay-based screen against a diverse panel of 54 plant polysaccharides was used to characterize the binding patterns of these new mAbs, together with 50 other previously generated mAbs, against plant cell wall glycans. Hierarchical clustering analysis was used to group these mAbs based on the polysaccharide recognition patterns observed. The mAb groupings in the resulting cladogram were further verified by immunolocalization studies in Arabidopsis (Arabidopsis thaliana) stems. The mAbs could be resolved into 19 clades of antibodies that recognize distinct epitopes present on all major classes of plant cell wall glycans, including arabinogalactans (both protein- and polysaccharide-linked), pectins (homogalacturonan, rhamnogalacturonan I), xyloglucans, xylans, mannans, and glucans. In most cases, multiple subclades of antibodies were observed to bind to each glycan class, suggesting that the mAbs in these subgroups recognize distinct epitopes present on the cell wall glycans. The epitopes recognized by many of the mAbs in the toolkit, particularly those recognizing arabinose- and/or galactose-containing structures, are present on more than one glycan class, consistent with the known structural diversity and complexity of plant cell wall glycans. Thus, these cell wall glycan-directed mAbs should be viewed and utilized as epitope-specific, rather than polymer-specific, probes. The current world-wide toolkit of approximately 180 glycan-directed antibodies from various laboratories provides a large and diverse set of probes for studies of plant cell wall structure, function, dynamics, and biosynthesis. PMID- 20363857 TI - New style, same substance. PMID- 20363860 TI - Photochemical proteolysis of an unstructured linker of the GABAAR extracellular domain prevents GABA but not pentobarbital activation. AB - The GABA type A receptor (GABA(A)R) is the major inhibitory receptor in the mammalian central nervous system and the target of numerous pharmaceuticals. The alpha-subunit of these pentameric Cys-loop neurotransmitter-gated ion channels contributes to the binding of both GABA and allosteric modulators such as the benzodiazepines, suggesting a role for this subunit in the conformational changes associated with activation of the receptor. Herein we use the nonsense suppression methodology to incorporate a photoactivatable unnatural amino acid and photochemically cleave the backbone of the alpha subunit of the alpha(1)beta(2) GABA(A)R in a linker region that is believed to span the subunit. Proteolytic cleavage impairs GABA but not pentobarbital activation, strongly suggesting that conformational changes involving this linker region are critical to the GABA activation pathway. PMID- 20363861 TI - New insights into the not-so-new NR3 subunits of N-methyl-D-aspartate receptor: localization, structure, and function. AB - The NR3 subunits (NR3A and NR3B) are new players in a well established field of N methyl-d-aspartate (NMDA) receptors, previously involving the NR1 and NR2 subunits. Their incorporation into conventional NMDA receptors forms glutamate activated NR1/NR2/NR3 triheteromers, whereas the omission of the glutamate binding NR2 subunits results in excitatory glycine-activated NR1/NR3 diheteromers. These NR3-containing NMDA receptors exhibit several differences in receptor properties compared with the conventional NR1/NR2 receptors. This review highlights the major landmarks that have been achieved in the past decade or so involving NR3 subunit research in four key areas: the spatiotemporal mapping of NR3 protein, the structural elucidation of NR3 domains, pharmacological characterization of NR3-containing receptors, and the successful generation of NR3 knockout/transgenic animals. It is expected that further characterization of their functional roles coupled with the identification of endogenous and exogenous ligands will eventually advance the understanding of the basic pharmacology and the complex role of NMDA receptors in higher brain functions and neurological disorders. PMID- 20363862 TI - An appraisal of the electrical resistance method for assessing root surface area. AB - Electrical resistances of roots and stems of hydroponically raised willows (Salix schwerinii) were studied and related to root morphology. Willow cuttings with and without roots were set in a constant electric field (effective voltage of 0.1 V, sine-AC, 128 Hz) in a hydroponic solution. The electrical resistance of different components in the measurement system was measured and analysed in relation to root surface area in contact with the cultivation solution. Axial resistivities of single root segments and of stems were measured. The results showed that the resistance decreased in relation to an increase in the contact surface area of the roots with the solution. The resistance depended strongly on the contact area of the stem with the solution, however, thus causing bias in the evaluation of root surface area. This work is a new contribution for the understanding of current pathways in the root system as exposed to an external electric field and for developing a non-destructive method to study plant roots accordingly. It may be concluded that the electrical resistance method is a useful non-destructive method to study roots and their physiological properties. Electrical analogues for roots and stem comprising resistors are discussed in relation to in situ measurements. PMID- 20363863 TI - The importance of nodule CO2 fixation for the efficiency of symbiotic nitrogen fixation in pea at vegetative growth and during pod formation. AB - Nodule CO2 fixation is of pivotal importance for N2 fixation. The process provides malate for bacteroids and oxaloacetate for nitrogen assimilation. The hypothesis of the present paper was that grain legume nodules would adapt to higher plant N demand and more restricted carbon availability at pod formation through increased nodule CO2 fixation and a more efficient N2 fixation. Growth, N2 fixation, and nodule composition during vegetative growth and at pod formation were studied in pea plants (Pisum sativum L.). In parallel experiments, 15N2 and 13CO2 uptake, as well as nodule hydrogen and CO2 release, was measured. Plants at pod formation showed higher growth rates and N2 fixation per plant when compared with vegetative growth. The specific activity of active nodules was about 25% higher at pod formation. The higher nodule activity was accompanied by higher amino acid concentration in nodules and xylem sap with a higher share of asparagine. Nodule 13CO2 fixation was increased at pod formation, both per plant and per 15N2 fixed unit. However, malate concentration in nodules was only 40% of that during vegetative growth and succinate was no longer detectable. The data indicate that increased N2 fixation at pod formation is connected with strongly increased nodule CO2 fixation. While the sugar concentration in nodules at pod formation was not altered, the concentration of organic acids, namely malate and succinate, was significantly lower. It is concluded that strategies to improve the capability of nodules to fix CO2 and form organic acids might prolong intensive N2 fixation into the later stages of pod formation and pod filling in grain legumes. PMID- 20363864 TI - Proteome profiling of early seed development in Cunninghamia lanceolata (Lamb.) Hook. AB - Knowledge of the proteome of the early gymnosperm embryo could provide important information for optimizing plant cloning procedures and for establishing platforms for research into plant development/regulation and in vitro transgenic studies. Compared with angiosperms, it is more difficult to induce somatic embryogenesis in gymnosperms; success in this endeavour could be increased, however, if proteomic information was available on the complex, dynamic, and multistage processes of gymnosperm embryogenesis in vivo. A proteomic analysis of Chinese fir seeds in six developmental stages was carried out during early embryogenesis. Proteins were extracted from seeds dissected from immature cones and separated by two-dimensional difference gel electrophoresis. Analysis with DeCyder 6.5 software revealed 136 spots that differed in kinetics of appearance. Analysis by liquid chromatography coupled to tandem mass spectrometry and MALDI TOF mass spectrometry identified proteins represented by 71 of the spots. Functional annotation of these seed proteins revealed their involvement in programmed cell death and chromatin modification, indicating that the proteins may play a central role in determining the number of zygotic embryos generated and controlling embryo patterning and shape remodelling. The analysis also revealed other proteins involved in carbon metabolism, methionine metabolism, energy production, protein storage, synthesis and stabilization, disease/defence, the cytoskeleton, and embryo development. The comprehensive protein expression profiles generated by our study provide new insights into the complex developmental processes in the seeds of the Chinese fir. PMID- 20363865 TI - The pollen tube journey in the pistil and imaging the in vivo process by two photon microscopy. AB - The process of pollen germination and tube growth in the pistil involves a series of cell-cell interactions, some facilitating fertilization while others prohibiting pollen tube access to the female gametophyte, either because of incompatibility or as a result of mechanisms to avert polyspermy and to ensure reproductive success. Understanding pollen tube growth and guidance to the female gametophyte has long been a pursuit among plant biologists, and observations indicate that diverse strategies may be adopted by different plant species. Recent studies in Arabidopsis, maize, and Torenia fournieri suggest that low molecular weight secretory molecules probably play major roles in the short-range attraction of pollen tubes to the female gametophyte. The process of pollen tube growth in the pistil occurs beneath several cell layers so much of the information that conveys the intimate partnership between penetrating pollen tubes and the female tissues has come from fixed samples and observations of in vitro pollen tube growth responses to female factors. A unique glimpse of the in vivo pollen germination and tube growth process is provided here by intra-vital two-photon excitation (TPE) microscopy of pollinated Arabidopsis pistils that remained on intact plants. Further discoveries of critical factors of male or female origins and how they control the pollen tube growth and fertilization process will broaden our understanding of the common themes and diverse strategies that plants have evolved to ensure reproductive success. The advancement of imaging technology to monitor pollination and fertilization and the development of probes to monitor various aspects of the pollen tube growth process, including pollen intracellular dynamics, will allow us to superimpose details obtained from studying pollen tube growth in culture conditions to interpret and understand the in vivo events. PMID- 20363866 TI - Acclimation kinetics of physiological and molecular responses of plants to multiple mechanical loadings. AB - During their development, plants are subjected to repeated and fluctuating wind loads, an environmental factor predicted to increase in importance by scenarios of global climatic change. Notwithstanding the importance of wind stress on plant growth and development, little is known about plant acclimation to the bending stresses imposed by repeated winds. The time-course of acclimation of young poplars (Populus tremula L.xP. alba L.) to multiple stem bendings is studied here by following diameter growth and the expression of four genes PtaZFP2, PtaTCH2, PtaTCH4, and PtaACS6, previously described to be involved in the mechanical signalling transduction pathway. Young trees were submitted either to one transient bending per day for several days or to two bendings, 1-14 days apart. A diminution of molecular responses to subsequent bending was observed as soon as a second bending was applied. The minimum rest periods between two successive loadings necessary to recover a response similar to that observed after a single bending, were 7 days and 5 days for growth and molecular responses, respectively. Taken together, our results show a desensitization period of a few days after a single transitory bending, indicating a day-scale acclimation of sensitivity to the type of wind conditions plants experience in their specific environment. This work establishes the basic kinetics of acclimation to low bending frequency and these kinetic analyses will serve as the basis of ongoing work to investigate the molecular mechanisms involved. Future research will also concern plant acclimation to higher wind frequencies. PMID- 20363867 TI - Characteristics of the tomato chromoplast revealed by proteomic analysis. AB - Chromoplasts are non-photosynthetic specialized plastids that are important in ripening tomato fruit (Solanum lycopersicum) since, among other functions, they are the site of accumulation of coloured compounds. Analysis of the proteome of red fruit chromoplasts revealed the presence of 988 proteins corresponding to 802 Arabidopsis unigenes, among which 209 had not been listed so far in plastidial databanks. These data revealed several features of the chromoplast. Proteins of lipid metabolism and trafficking were well represented, including all the proteins of the lipoxygenase pathway required for the synthesis of lipid-derived aroma volatiles. Proteins involved in starch synthesis co-existed with several starch-degrading proteins and starch excess proteins. Chromoplasts lacked proteins of the chlorophyll biosynthesis branch and contained proteins involved in chlorophyll degradation. None of the proteins involved in the thylakoid transport machinery were discovered. Surprisingly, chromoplasts contain the entire set of Calvin cycle proteins including Rubisco, as well as the oxidative pentose phosphate pathway (OxPPP). The present proteomic analysis, combined with available physiological data, provides new insights into the metabolic characteristics of the tomato chromoplast and enriches our knowledge of non photosynthetic plastids. PMID- 20363868 TI - Recondensation level of repetitive sequences in the plant protoplast nucleus is limited by oxidative stress. AB - Protoplast cultures are remarkable examples of plant cell dedifferentiation. The state of dedifferentiation is evidenced by changes in cell morphology, genome organization, as well as by the capability of protoplasts to differentiate into multiple types of cells (depending on the type of the stimulus applied). The first change in the genome structure is connected with large-scale chromatin decondensation, affecting chromocentres involving various types of these repetitive sequences. This paper describes not only the de- and recondensation of satellite DNA type I and 5S rDNA repetitive sequences, but it also compares the recondensation level of chromatin with the levels of oxidative stress which were decreased by using an antioxidant, as well as the capabilities of the antioxidative systems within protoplasts, during the first 72 h of their culture. It is demonstrated that the treatment of protoplasts with ascorbic acid not only decreased the level of oxidative stress but also positively stimulated the expression of the ascorbate peroxidase and catalase. It also led to a greater recondensation of the chromatin (when compared to the untreated protoplasts); in addition, it supported cell proliferation. It is concluded that large-scale genome relaxation is more directly connected with oxidative stress than with large changes in the expression of genes; and further, that its recondensation is related to the start of (as well as the level of) protection by the antioxidative systems. PMID- 20363869 TI - Analysis of five novel putative constitutive gene promoters in transgenic rice plants. AB - Novel constitutive gene promoters are essential components of crop biotechnology. Our analysis of five such promoters, APX, SCP1, PGD1, R1G1B, and EIF5, in transgenic rice plants is reported here. The five promoter regions were linked to the gfp reporter gene and transformed into rice. Using fluorescent microscopy and q-RT-PCR, promoter activities were analysed in comparison with OsCc1, Act1, and ZmUbi1, previously characterized as strong constitutive promoters. The APX and PGD1 promoters direct high levels of gene expression in all tissues and stages, producing GFP at levels of up to 1.3% of the total soluble protein. PGD1 is particularly active in flowers and mature roots. The R1G1B is active in the whole grain including the embryo, endosperm, and aleurone layer, and thus represents a constitutive promoter with activity in whole seeds that has not been described previously. The ZmUbi1 and R1G1B promoters are markedly less active in young roots and mature leaves whilst the APX, PGD1, OsCc1, and Act1 promoters are highly active in both vegetative and reproductive tissues. Overall, our results demonstrate that APX, PGD1, and R1G1B are novel gene promoters that are highly active at all stages of plant growth with distinct levels of activity. PMID- 20363870 TI - Pollen-pistil interactions and the endomembrane system. AB - The endomembrane system offers many potential points where plant mating can be effectively controlled. This results from two basic features of angiosperm reproduction: the requirement for pollen tubes to pass through sporophytic tissues to gain access to ovules and the physiology of pollen tube growth that provides it with the capacity to do so. Rapid pollen tube growth requires extravagant exocytosis and endocytosis activity as cell wall material is deposited and membrane is recovered from the actively growing tip. Moreover, recent results show that pollen tubes take up a great deal of material from the pistil extracellular matrix. Regarding the stigma and style as organs specialized for mate selection focuses attention on their complementary roles in secreting material to support the growth of compatible pollen tubes and discourage the growth of undesirable pollen. Since these processes also involve regulated activities of the endomembrane system, the potential for regulating mating by controlling endomembrane events exists in both pollen and pistil. PMID- 20363871 TI - Rubisco activities, properties, and regulation in three different C4 grasses under drought. AB - In C4 plants, water deficit may decrease photosynthetic CO2 assimilation independently of changes in stomatal conductance, suggesting decreased turnover by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The activity and biochemistry of Rubisco was studied in three different C4 grasses: Paspalum dilatatum, Cynodon dactylon, and Zoysia japonica. The objectives were to characterize the C4 Rubisco in these species and to identify factors associated with decreased photosynthetic rates caused by drought. Rubisco isolated from each of the three C4 grasses was characterized by smaller specificity factors (SC/O), larger Michaelis-Menten constants for CO2 (Kc) and O2 (Ko), and larger maximum carboxylation velocities (Vc) than Rubisco from wheat, which can be rationalized in terms of the CO2-rich environment of C4 Rubisco in the bundle sheath. During leaf dehydration the quantity and maximum activity of Rubisco remained unchanged but the initial and total activities declined slightly, possibly due to increased inhibition. Tight-binding inhibitors were present in the light but were more abundant in the dark, especially in Z. japonica, and increased in quantity with drought stress. The inhibitor from darkened leaves of Z. japonica was identified as 2-carboxyarabinitol-1-phosphate (CA1P). Consistent with the presence of CA1P, the total activity of Rubisco was decreased after 12 h darkness in Z. japonica. Ribulose-1,5-bisphosphate (RuBP) in the leaves decreased with drought stress, to quantities approximating those of Rubisco catalytic sites. The magnitude of the decrease in RuBP suggested that, at least in C. dactylon and Z. japonica, it could contribute to the drought-induced decrease in photosynthesis. PMID- 20363872 TI - Sensory gating event-related potentials and oscillations in schizophrenia patients and their unaffected relatives. AB - BACKGROUND: The P50 event-related potential sensory gating deficit, a failure to inhibit responses to repeated stimuli, is a leading endophenotype for schizophrenia (SZ). Both gamma and beta event-related oscillations (EROs) are major contributors to the auditory P50 response. However, the topographic distribution of gamma and beta ERO responses to initial (S1) and repeat (S2) stimuli and the association of these oscillations with P50 sensory gating are not clear. METHODS: A total of 51 schizophrenic patients, 25 unaffected first-degree relatives, and 34 healthy comparison subjects were tested using a paired-click paradigm. Evoked power of gamma- and beta-band responses using wavelet analyses to S1 and S2 stimuli and gating of EROs and P50 were the main outcome measures. RESULTS: A P50 gating deficit was found in patients (P < .001) and at a trend level in relatives (P = .087). Patients showed widely distributed reductions in gamma and beta EROs to S1 stimuli and S2 stimuli, respectively, and impaired gating in both frequencies. Reduced gamma and beta ERO activity in patients was associated primarily with age of onset. Relatives did not differ significantly from control subjects in either EROs power or gating. Gating of P50, gamma, and beta were not significantly correlated (r = .18-.19, P > .05). CONCLUSIONS: These results suggest that ERO deficits in gamma to S1 and beta to S2 stimuli and impaired ERO gating are associated with SZ, but are not related to genetic liability for the illness. The components of information processing assessed by gamma- and beta gating appear to be independent from those mediated by P50 suppression. PMID- 20363873 TI - Revisiting Arieti's "listening attitude" and hallucinated voices. AB - Silvano Arieti proposed that auditory/verbal hallucinations (AVHs) are triggered by momentary states of heightened auditory attention that he identified as a "listening attitude." Studies and clinical observations by our group support this view. Patients enrolled in our repetitive transcranial magnetic stimulation trials, if experiencing a significant curtailment of these hallucinations, often report an episodic sense that their voices are still occurring even if they no longer can be heard, suggesting episodic states of heightened auditory expectancy. Moreover, a functional magnetic resonance study reported by our group detected activation in the left insula prior to hallucination events. This finding is suggestive of activation in the same region detected in healthy subjects during "auditory search" in response to ambiguous sounds when anticipating meaningful speech. AVHs often are experienced with a deep emotional salience and may occur in the context of dramatic social isolation that together could reinforce heightened auditory expectancy. These findings and clinical observations suggest that Arieti's original formulation deserves further study. PMID- 20363874 TI - AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation. AB - AMP-activated protein kinase (AMPK) inhibits IGF-I actions, but the mechanism by which AMPK functions is undefined. This study identified signaling events that were induced by AMPK that mediated inhibition of IGF-I-stimulated phosphoinosotide-3-kinase (PI3K) pathway activation. The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K). Expression of constitutively active forms of AMPK suppressed IGF-I-stimulated activation of Akt/TSC2/mTOR/p70S6K and protein synthesis, whereas AMPK knockdown resulted in enhanced responses to IGF-I. To determine the mechanism by which AMPK inhibited IGF-I signaling, the role of insulin receptor substrate-1 (IRS-1) was examined. Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K. Overexpression of IRS-1 S794A was associated with increased IGF-I stimulated IRS-1 tyrosine phosphorylation, p85 association, and protein synthesis. To determine whether other signaling molecules mediated the effect of AMPK, TSC2 function was examined. Cells overexpressing TSC2/S1345A (the site of AMPK phosphorylation) were less responsive to metformin-induced inhibition of p70S6 kinase. These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K. In conclusion, AMPK functions to inhibit IGF I-stimulated PI3K pathway activation through stimulation of IRS-1 serine 794 phosphorylation. Because IGF-I is an important stimulant of the anabolic response, this effect of AMPK could account for part of its inhibitory effect on protein synthesis, thus allowing more efficient energy use by other cellular processes. PMID- 20363875 TI - Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. AB - Bone morphogenetic proteins (BMPs) have diverse roles in development and reproduction. Although several BMPs are produced by oocytes, thecal cells, and granulosa cells of developing follicles, the in vivo functions of most of these ligands are unknown. BMP signals are transduced by multiple type I and type II TGFbeta family receptors, and of the type I receptors, BMP receptor 1A (BMPR1A) and BMP receptor 1B (BMPR1B) are known to be expressed in rodent granulosa cells. Female mice homozygous null for Bmpr1b are sterile due to compromised cumulus expansion, but the function of BMPR1A in the ovary is unknown. To further decipher a role for BMP signaling in mouse granulosa cells, we deleted Bmpr1a in the granulosa cells of the ovary and found Bmpr1a conditional knockout females to be subfertile with reduced spontaneous ovulation. To explore the redundant functions of BMP receptor signaling in the ovary, we generated Bmpr1a Bmpr1b double-mutant mice, which developed granulosa cell tumors that have evidence of increased TGFbeta and hedgehog signaling. Thus, similar to SMAD1 and SMAD5, which have redundant roles in suppressing granulosa cell tumor development in mice, two type I BMP receptors, BMPR1A and BMPR1B, function together to prevent ovarian tumorigenesis. These studies support a role for a functional BMP signaling axis as a tumor suppressor pathway in the ovary, with BMPR1A and BMPR1B acting downstream of BMP ligands and upstream of BMP receptor SMADs. PMID- 20363877 TI - Identification and characterization of a promoter cassette conferring adipocyte specific gene expression. AB - The adipocyte-specific secretory molecule adiponectin has found widespread acceptance as a systemic marker that effectively integrates a number of signals associated with metabolic dysfunction at the level of adipose tissue. The widely used aP2 promoter cassette, which is frequently chosen to achieve adipocyte specific expression of transgenes, conveys transcription in cell types other than adipocytes, such as macrophages and cardiomyocytes. To improve our ability to drive transgene expression in a more adipocyte-specific way, we aimed to define the minimal promoter segment from the adiponectin genomic locus. We generated a series of transgenic animals in which the expression of reporter genes and Cre recombinase was driven by 2, 4.9, and 5.4 kb of adiponectin promoter sequences. We found that the 5.4-kb adiponectin promoter fragment is the most effective cassette conveying adipocyte-specific expression of target genes. We therefore define a novel promoter cassette that ensures adipocyte-specific expression of passenger genes and may be used in the generation of transgenic mouse models to study gene function in vivo. PMID- 20363876 TI - Minireview: Estrogen receptor-beta: mechanistic insights from recent studies. AB - The discovery of estrogen receptor-beta (ERbeta) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERbeta action. We now know that ERbeta plays a major role in mediating estrogen action in several tissues and organ systems, including the ovary, cardiovascular system, brain, and the immune system, and that ERbeta and ERalpha generally play distinct physiological roles in the body. Although significant progress has been made toward understanding the molecular mechanisms of ERbeta action, particularly in vitro, there remains a large gap in our understanding of the mechanisms by which ERbeta elicits its biological functions in a true physiological context. PMID- 20363878 TI - Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors. AB - Several Toll-like receptors (TLRs) are expressed in Sertoli cells and can trigger testicular innate responses after activation by ligands. TLR signaling pathway must be tightly controlled because unrestrained TLR activation generates a chronic inflammatory milieu that often leads to pathogenesis of the host. However, the regulation of TLR signaling in Sertoli cells remains to be clarified. Here we demonstrate that Tyro3 subfamily of receptor tyrosine kinases, Tyro3, Axl, and Mer (TAM), negatively regulate TLR3 signaling in Sertoli cells. Sertoli cells from TAM triple mutant (TAM(-/-)) mice exhibit an excessive activation of TLR3 in response to its ligand polyinosinic-polycytidylic acid, resulting in the up-regulation of inflammatory cytokines including IL-1beta, IL 6, TNFalpha, and type I interferons (alpha and beta). Growth arrest-specific gene 6 (Gas6), a common ligand of TAM receptors, inhibits the TLR3-driven expression of cytokines in Sertoli cells. This TAM-mediated inhibition of TLR3 signaling in Sertoli cells is transduced through the up-regulation of TLR signaling suppressors suppressor of cytokine signaling-1/3 by Gas6. Moreover, we provide evidence that TAM inhibition of inflammatory cytokine production by Sertoli cells may have physiological significance in vivo. These results illuminate a negative regulatory mechanism of TLR3 signaling in Sertoli cells, which may participate in controlling the testicular innate immune responses to pathogens. PMID- 20363879 TI - GLP-1(7-36)-amide and Exendin-4 stimulate the HPA axis in rodents and humans. AB - Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic peptide expressed in the gut and brain, which is secreted in response to food intake. The levels of GLP-1 within the brain have been related to the activity of the hypothalamic pituitary-adrenal (HPA) axis, and hence, this peptide might mediate some responses to stress. Nevertheless, there is little information regarding the effects of circulating GLP-1 on the neuroendocrine control of HPA activity. Here, we have studied the response of corticoadrenal steroids to the peripheral administration of GLP-1 (7-36)-amide and related peptides [exendin (Ex)-3, Ex-4, and Ex-4(3-39)] in rats, mice, and humans. GLP-1 increases circulating corticosterone levels in a time-dependent manner, both in conscious and anaesthetized rats, and it has also increased aldosterone levels. Moreover, GLP-1 augmented cortisol levels in healthy subjects and diabetes mellitus (DM)-1 patients. The effects of GLP-1/Ex-4 on the HPA axis are very consistent after distinct means of administration (intracerebroventricular, iv, and ip), irrespective of the metabolic state of the animals (fasting or fed ad libitum), and they were reproduced by different peptides in this family, independent of glycaemic changes and their insulinotropic properties. Indeed, these effects were also observed in diabetic subjects (DM-1 patients) and in the DM-1 streptozotocin rat or DM-2 muscle IGF-I receptor-lysine-arginine transgenic mouse animal models. The mechanisms whereby circulating GLP-1 activates the HPA axis remain to be elucidated, although an increase in ACTH after Ex-4 and GLP-1 administration implicates the central nervous system or a direct effect on the pituitary. Together, these findings suggest that GLP-1 may play an important role in regulating the HPA axis. PMID- 20363880 TI - Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-{alpha}. AB - Chemerin is an adipokine with important regulatory roles in adipogenesis. In humans, serum total chemerin (i.e. prochemerin plus chemerin) levels are positively associated with body mass index and metabolic syndrome. However, the mechanisms that increase serum chemerin concentration are unknown. We hypothesized that chronic low-grade inflammation that occurs in obesity promotes chemerin production by adipocytes. Consistent with this, TNFalpha treatment of 3T3-L1 adipocytes increased bioactive chemerin levels in the cell media as detected using a CMKLR1 cell-based bioassay. This effect was blocked by the protein synthesis inhibitor cycloheximide and protein secretion inhibitor brefeldin A, indicating that TNFalpha may enhance prochemerin synthesis and secretion from adipocytes. In vivo, TNFalpha produced a time-dependent increase in serum total chemerin and bioactive chemerin. Bioactive chemerin was produced by primary mouse adipocytes and hepatocytes. Only primary adipocyte-derived chemerin was responsive to TNFalpha regulation implicating adipocytes as a potential source of elevated serum chemerin after TNFalpha exposure in vivo. In lean mice, serum total chemerin levels oscillated with peak levels occurring during daytime and trough levels at night. Comparatively, leptin- and leptin receptor-deficient obese mice, which have elevated adipose tissue expression of TNFalpha, displayed elevated serum total chemerin levels with an enhanced oscillatory pattern. In summary, our novel results identified TNFalpha as a positive regulator of adipocyte-derived chemerin. We corroborate the finding of elevated chemerin in obese humans by identifying elevated serum levels of total chemerin in two obese mouse models with a corresponding alteration in the rhythmic pattern of serum chemerin levels. PMID- 20363881 TI - Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion. AB - Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments ( approximately 1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca(2+) responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p) eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca(2+) levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer(1179)) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary animals. These data provide new insights into exercise training-induced adaptations in cellular mechanisms of nitric oxide regulation in collateral-dependent coronary arteries of chronically occluded hearts that contribute to enhanced nitric oxide production. PMID- 20363882 TI - Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules. AB - Endothelial properties are affected by mechanical stresses. Several studies have shown that an acute application of shear stress increases the permeability of endothelial monolayers in culture. We investigated whether more prolonged application of shear has the opposite effect. Porcine aortic endothelial cells were cultured on Transwell filters to assess monolayer permeability to albumin. The medium above the cells was swirled using an orbital shaker; resultant shears were computed to lie within the physiological range. Acute application of shear increased permeability, but chronic application reduced it. The effect of chronic but not acute shear was reversed by inhibiting nitric oxide (NO) synthesis. The effect of chronic shear was also reversed by inhibiting phosphatidylinositol 3-OH kinase (PI3K) and soluble guanylyl cyclase. None of these interventions affected permeability under static conditions, and inhibition of cyclooxygenase was without effect. Chronic shear decreased mitosis rates by a fraction comparable to the reduction in permeability, but this effect was not reversed by inhibiting NO synthesis. We conclude that chronic application of shear stress reduces endothelial permeability to macromolecules by a PI3K-NO-cGMP-dependent mechanism. Since atherosclerosis can be triggered by excessive entry of plasma macromolecules into the arterial wall, the phenomenon may help explain the atheroprotective effects of shear and NO. PMID- 20363883 TI - Properties of WT and mutant hERG K(+) channels expressed in neonatal mouse cardiomyocytes. AB - Mutations in human ether-a-go-go-related gene 1 (hERG) are linked to long QT syndrome type 2 (LQT2). hERG encodes the pore-forming alpha-subunits that coassemble to form rapidly activating delayed rectifier K(+) current in the heart. LQT2-linked missense mutations have been extensively studied in noncardiac heterologous expression systems, where biogenic (protein trafficking) and biophysical (gating and permeation) abnormalities have been postulated to underlie the loss-of-function phenotype associated with LQT2 channels. Little is known about the properties of LQT2-linked hERG channel proteins in native cardiomyocyte systems. In this study, we expressed wild-type (WT) hERG and three LQT2-linked mutations in neonatal mouse cardiomyocytes and studied their electrophysiological and biochemical properties. Compared with WT hERG channels, the LQT2 missense mutations G601S and N470D hERG exhibited altered protein trafficking and underwent pharmacological correction, and N470D hERG channels gated at more negative voltages. The DeltaY475 hERG deletion mutation trafficked similar to WT hERG channels, gated at more negative voltages, and had rapid deactivation kinetics, and these properties were confirmed in both neonatal mouse cardiomyocyte and human embryonic kidney (HEK)-293 cell expression systems. Differences between the cardiomyocytes and HEK-293 cell expression systems were that hERG current densities were reduced 10-fold and deactivation kinetics were accelerated 1.5- to 2-fold in neonatal mouse cardiomyocytes. An important finding of this work is that pharmacological correction of trafficking-deficient LQT2 mutations, as a potential innovative approach to therapy, is possible in native cardiac tissue. PMID- 20363884 TI - Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice. AB - Treating cancer patients with chemotherapeutics, such as doxorubicin (Dox), cause dilated cardiomyopathy and congestive heart failure because of oxidative stress. On the other hand, heat shock factor-1 (HSF-1), a transcription factor for heat shock proteins (Hsps), is also known to be activated in response to oxidative stress. However, the possible role of HSF-1 activation and the resultant Hsp25 in chemotherapeutic-induced heart failure has not been investigated. Using HSF-1 wild-type (HSF-1(+/+)) and knock-out (HSF-1(-/-)) mice, we tested the hypothesis that activation of HSF-1 plays a role in the development of Dox-induced heart failure. Higher levels of Hsp25 and its phosphorylated forms were found in the failing hearts of Dox-treated HSF-1(+/+) mice. More than twofold increase in Hsp25 mRNA level was found in Dox-treated hearts. Proteomic analysis showed that there is accumulation and aggregation of Hsp25 in Dox-treated failing hearts. Additionally, Hsp25 was found to coimmunoprecipitate with p53 and vice versa. Further studies indicated that the Dox-induced higher levels of Hsp25 transactivated p53 leading to higher levels of the pro-apoptotic protein Bax, but other p53-related proteins remained unaltered. Moreover, HSF-1(-/-) mice showed significantly reduced Dox-induced heart failure and higher survival rate, and there was no change in Bax upon treating with Dox in HSF-1(-/-) mice. From these results we propose a novel mechanism for Dox-induced heart failure: increased expression of Hsp25 because of oxidant-induced activation of HSF-1 transactivates p53 to increase Bax levels, which leads to heart failure. PMID- 20363885 TI - Roles of hyperpolarization-activated current If in sinoatrial node pacemaking: insights from bifurcation analysis of mathematical models. AB - To elucidate the roles of hyperpolarization-activated current (I(f)) in sinoatrial node (SAN) pacemaking, we theoretically investigated 1) the effects of I(f) on stability and bifurcation during hyperpolarization of SAN cells; 2) combined effects of I(f) and the sustained inward current (I(st)) or Na(+) channel current (I(Na)) on robustness of pacemaking against hyperpolarization; and 3) whether blocking I(f) abolishes pacemaker activity under certain conditions. Bifurcation analyses were performed for mathematical models of rabbit SAN cells; equilibrium points (EPs), periodic orbits, and their stability were determined as functions of parameters. Unstable steady-state potential region determined with applications of constant bias currents shrunk as I(f) density increased. In the central SAN cell, the critical acetylcholine concentration at which bifurcations, to yield a stable EP and quiescence, occur was increased by smaller I(f), but decreased by larger I(f). In contrast, the critical acetylcholine concentration and conductance of gap junctions between SAN and atrial cells at bifurcations progressively increased with enhancing I(f) in the peripheral SAN cell. These effects of I(f) were significantly attenuated by eliminating I(st) or I(Na), or by accelerating their inactivation. Under hyperpolarized conditions, blocking I(f) abolished SAN pacemaking via bifurcations. These results suggest that 1) I(f) itself cannot destabilize EPs; 2) I(f) improves SAN cell robustness against parasympathetic stimulation via preventing bifurcations in the presence of I(st) or I(Na); 3) I(f) dramatically enhances peripheral cell robustness against electrotonic loads of the atrium in combination with I(Na); and 4) pacemaker activity of hyperpolarized SAN cells could be abolished by blocking I(f). PMID- 20363886 TI - Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide (O(2)(-)) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 + or - 2.9% in WKY Af-Arts but fell by 29.3 + or - 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af Arts compared with WKY Af-Arts (SHR, 48.0 + or - 2.2%; and WKY, 12.2 + or - 0.3%). To test whether O(2)(-) contributes to the myogenic response in SHRs, either the membrane-permeant O(2)(-) scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol (10(-4) M) and gp91ds-tat (10(-5) M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived O(2)(-) may contribute to the enhanced myogenic response, and 3) O(2)(-) exerts little influence on the myogenic response under normotensive conditions. PMID- 20363888 TI - Regulation of the voltage-insensitive step of HERG activation by extracellular pH. AB - Human ether-a-go-go-related gene (HERG, Kv11.1, KCNH2) voltage-gated K(+) channels dominate cardiac action potential repolarization. In addition, HERG channels play a role in neuronal and smooth cell excitability as well as cancer pathology. Extracellular pH (pH(o)) is modified during myocardial ischemia, inflammation, and respiratory alkalosis, so understanding the response of HERG channels to changes in pH is of clinical significance. The relationship between pH(o) and HERG channel gating appears complex. Acidification has previously been reported to speed, slow, or have no effect on activation. We therefore undertook comprehensive analysis of the effect of pH(o) on HERG channel activation. HERG channels have unique and complex activation gating characteristics with both voltage-sensitive and voltage-insensitive steps in the activation pathway. Acidosis decreased the activation rate, suppressed peak current, and altered the sigmoidicity of gating near threshold potentials. At positive voltages, where the voltage-insensitive transition is rate limiting, pH(o) modified the voltage insensitive step with a pK(a) similar to that of histidine. Hill coefficient analysis was incompatible with a coefficient of 1 but was well described by a Hill coefficient of 4. We derived a pH(o)-sensitive term for a five-state Markov model of HERG channel gating. This model demonstrates the mechanism of pH(o) sensitivity in HERG channel activation. Our experimental data and mathematical model demonstrate that the pH(o) sensitivity of HERG channel activation is dominated by the pH(o) sensitivity of the voltage-insensitive step, in a fashion that is compatible with the presence of at least one proton-binding site on each subunit of the channel tetramer. PMID- 20363887 TI - Effects of cardiac-restricted overexpression of the A(2A) adenosine receptor on adriamycin-induced cardiotoxicity. AB - Activation of the A(2A) adenosine receptor (A(2A)R) has been shown to be cardioprotective. We hypothesized that A(2A)R overexpression could protect the heart from adriamycin-induced cardiomyopathy. Transgenic (TG) mice overexpressing the A(2A)R and wild-type mice (WT) were injected with adriamycin (5 mg.kg(-1).wk( 1) ip, 4 wk). All WT mice survived adriamycin treatment while A(2A)R TG mice suffered 100% mortality at 4 wk. Telemetry showed progressive prolongation of the QT interval, bradyarrhythmias, heart block, and sudden death in adriamycin treated A(2A)R TG but not WT mice. Both WT and A(2A)R TG demonstrated similar decreases in heart function at 3 wk after treatment. Adriamycin significantly increased end-diastolic intracellular Ca(2+) concentration in A(2A)R TG but not in WT myocytes (P < 0.05). Compared with WT myocytes, action potential duration increased dramatically in A(2A)R TG myocytes (P < 0.05) after adriamycin treatment. Expression of connexin 43 was decreased in adriamycin treated A(2A)R TG but not WT mice. In sharp contrast, A(2A)R overexpression induced after the completion of adriamycin treatment resulted in no deaths and enhanced cardiac performance compared with WT adriamycin-treated mice. Our results indicate that the timing of A(2A)R activation is critical in terms of exacerbating or protecting adriamycin-induced cardiotoxicity. Our data have direct relevance on the clinical use of adenosine agonists or antagonists in the treatment of patients undergoing adriamycin therapy. PMID- 20363889 TI - A biophysical model for cardiac microimpedance measurements. AB - Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements taken on top of the currents flowing in active tissue. In particular, our results show that measurements taken at multiple frequencies and electrode separations provide powerful predictions of the underlying tissue resistances in all geometric dimensions. Because of the small electrode size, separation of interstitial from intracellular compartment contributions is readily achieved. PMID- 20363890 TI - AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation. AB - Using neonatal rat ventricular myocytes, we previously reported that the expression of a dominant negative form of the c-Fos proto-oncogene (AFos) inhibited activator protein 1 activity and blocked the induction of the pathological gene profile stimulated by phenylephrine (PE) while leaving growth unaffected. We now extend these observations to the adult rat ventricular myocyte (ARVM) to understand the relationship between gene expression, growth, and function. Ventricular myocytes were isolated from adult rats and infected with adenovirus expressing beta-galactosidase (control) or AFos. The cells were subsequently treated with PE, and protein synthesis, gene program, calcium transients, and contractility were evaluated. As seen with the neonatal rat ventricular myocytes, in control cells PE stimulated an increase in protein synthesis, induced the pathological gene profile, and exhibited both depressed contractility and calcium transients. Although ARVMs expressing AFos still had PE induced growth, pathological gene expression as well as contractility and calcium handling abnormalities were inhibited. To determine a possible mechanism of the preserved myocyte function in AFos-expressing cells, we examined phospholamban (PLB) and sarco(endo)plasmic reticulum calcium-ATPase proteins. Although there was no change in total PLB or sarco(endo)plasmic reticulum calcium-ATPase expression in response to PE treatment, PE decreased the phosphorylation of PLB at serine-16, an observation that was prevented in AFos-expressing cells. In conclusion, although PE-induced growth was unaffected in AFos-expressing ARVMs, the expression of the pathological gene profile was inhibited and both contractile function and calcium cycling were preserved. The inhibition of functional deterioration was, in part, due to the preservation of PLB phosphorylation. PMID- 20363891 TI - Sensitivity of NOS-dependent vascular relaxation pathway to mineralocorticoid receptor blockade in caveolin-1-deficient mice. AB - Endothelial caveolin-1 (cav-1) is an anchoring protein in plasma membrane caveolae where it binds endothelial nitric oxide synthase (eNOS) and limits its activation, particularly in animals fed a high salt (HS) diet. Cav-1 also interacts with steroid receptors such as the mineralocorticoid receptor (MR). To test the hypothesis that vascular reactivity is influenced by an interplay between MR and cav-1 during HS diet, we examined the effects of MR blockade on NOS-mediated vascular relaxation in normal and cav-1-deficient mice. Wild-type (WT) and cav-1 knockout mice (cav-1(-/-)) were fed for 14 days a HS (4% NaCl) diet with and without the MR antagonist eplerenone (Epl; 100 mg x kg(-1) x day( 1)). After systolic blood pressure (BP) was measured, the thoracic aorta was isolated for measurement of vascular reactivity, and the aorta and heart were used for measurement of eNOS and MR expression. BP was not different between WT + Epl and WT, but was higher in cav-1(-/-) + Epl than in cav-1(-/-) mice. Phenylephrine (Phe)-induced vascular contraction was less in cav-1(-/-) than WT, and significantly enhanced in cav-1(-/-) + Epl than in cav-1(-/-), but not in WT + Epl compared with WT. Endothelium removal and NOS blockade by N(omega)-nitro-l arginine methyl ester (l-NAME) enhanced Phe contraction in cav-1(-/-), but not cav-1(-/-) + Epl. ACh-induced aortic relaxation was reduced in cav-1(-/-) + Epl versus cav-1(-/-), but not in WT + Epl compared with WT. Endothelium removal, l NAME, and the guanylate cyclase inhibitor ODQ abolished the large ACh-induced relaxation in cav-1(-/-) and the remaining relaxation in the cav-1(-/-) + Epl but had similar inhibitory effect in WT and WT + Epl. Real-time RT-PCR indicated decreased eNOS mRNA expression in the aorta and heart, and Western blots revealed decreased total eNOS in the heart of cav-1(-/-) + Epl compared with cav-1(-/-). Vascular and cardiac MR expression was less in cav-1(-/-) than WT, but not in cav 1(-/-) + Epl compared with cav-1(-/-). Plasma aldosterone (Aldo) was not different between WT and cav-1(-/-) mice nontreated or treated with Epl. Thus in cav-1 deficiency states and HS diet MR blockade is associated with increased BP, enhanced vasoconstriction, and decreased NOS-mediated vascular relaxation and eNOS expression. The data suggest that, in the absence of cav-1, MR activation plays a beneficial role in regulating eNOS expression/activity and, consequently, the vascular function during HS diet. PMID- 20363892 TI - Akt1 genetic deficiency limits hypothermia cardioprotection following murine cardiac arrest. AB - Therapeutic hypothermia (TH) cardioprotection has recently been associated with increased Akt signaling in a rat model of cardiac arrest. However, it is not known whether Akt is required for this beneficial effect of TH. We used a mouse model of cardiac arrest demonstrating TH cardioprotection to study the response of mice deficient in an Akt1 allele. We hypothesized that Akt1 mediates TH cardioprotection and that decreases in Akt1 content would diminish such protection. Adult C57BL/6 wild-type (WT) mice underwent an 8-min cardiac arrest. After 6 min, the mice were randomized to normothermia (WT(NT), 37 degrees C) or TH (WT(TH), 30 degrees C). Following cardiopulmonary resuscitation and the return of spontaneous circulation (ROSC), the animals were hemodynamically monitored for 240 min (R240). At R240, cardiac tissue Akt content and phosphorylation were assayed. Studies were repeated in Akt1 heterozygous (Akt1(+/-)) mice. As a result, baseline characteristics and ROSC rates were equivalent across groups. At R240, WT(TH) mice exhibited lower heart rate, larger stroke volume, and higher cardiac output than WT(NT) animals (P < 0.05). Cardioprotection in WT(TH) at R240 was associated with increased cardiac Akt phosphorylation at Ser473 and Thr308 compared with that in WT(NT) (P < 0.05). TH-associated alterations in Akt phosphorylation, stroke volume, heart rate, and cardiac output were abrogated in Akt1(+/-) animals. In conclusion, TH improves post-ROSC cardiac function and increases Akt phosphorylation in WT, but not Akt1(+/-), mice. The Akt1 isoform appears necessary for TH-mediated cardioprotection. PMID- 20363893 TI - Transgenic mice expressing an intracellular fluorescent fusion of angiotensin II demonstrate renal thrombotic microangiopathy and elevated blood pressure. AB - We have generated transgenic mice that express angiotensin II (ANG II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole-animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung, and testes), and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating ANG II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated, and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry (n = 8 for each group), were significantly higher in transgenic mice compared with wild-type littermates. Blood pressure of line A male transgenic mice was 125 + or - 1.7 over 97 + or - 1.6 compared with 109 + or - 1.7 over 83 + or - 1.4 mmHg in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of ANG II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension. PMID- 20363894 TI - Vulnerable windows define susceptibility to alternans and spatial discordance. AB - Electrophysiological alternans is a beat-to-beat alternation of the action potential duration and/or Ca(2+) transient amplitude and is linked to ventricular arrhythmias. We investigated the significance of various rate parameters under different experimental conditions with respect to alternans incidence and the propensity for spiral wave formation. Voltage and Ca(2+) were optically mapped in monolayers of neonatal rat ventricular myocytes. Alternans did not occur at physiological temperature, but its incidence increased significantly at lowered temperatures. Pacing cycle length for spatially concordant alternans onset (PCL(C)), PCL for spatially discordant alternans onset (PCL(D)), and minimum cycle length for loss of 1:1 or 2:2 capture (MCL) also significantly increased with lower temperature but in a way such that the differences between PCL(C) and MCL and between PCL(D) and MCL widened. These results provided the rationale to identify the former difference as the alternans vulnerable window (AVW; in ms) and the latter difference as the discordant alternans vulnerable window (AVW(D); in ms). Computational simulations showed that interventions that widen AVW, including altered Ca(2+) cycling and enhanced K(+) currents, also promote alternans, regardless of whether PCL(C) or MCL increased or decreased. The simulation results were confirmed experimentally by addition of the ATP-sensitive K(+) channel agonist pinacidil. Mathematical analysis provided a theoretical basis linking the size of AVW to the incidence of alternans. Finally, experiments showed that the size of AVW(D) is related to the incidence of spatially discordant alternans and, additionally, to the incidence of spiral wave formation. In conclusion, vulnerable windows can be defined that are strongly correlated with alternans incidence, spatial discordance, and spiral wave formation. PMID- 20363895 TI - Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage. AB - Circulating endothelial cells (CECs) are nonhematopoetic mononuclear cells in peripheral blood that are dislodged from injured vessels during cardiovascular disease, systemic vascular disease, and inflammation. Their occurrence during cerebrovascular insults has not been previously described. Epileptic seizures cause the long-term loss of cerebrovascular endothelial dilator function. We hypothesized that seizures cause endothelial sloughing from cerebral vessels and the appearance of brain-derived CECs (BCECs), possible early indicators of cerebral vascular damage. Epileptic seizures were induced by bicuculline in newborn pigs; venous blood was then sampled during a 4-h period. CECs were identified in the fraction of peripheral blood mononuclear cells by the expression of endothelial antigens (CD146, CD31, and endothelial nitric oxide synthase) and by Ulex europeaus lectin binding. In control animals, few CECs were detected. Seizures caused a time-dependent increase in CECs 2-4 h after seizure onset. Seizure-induced CECs coexpress glucose transporter-1, a blood-brain barrier-specific glucose transporter, indicating that these cells originate in the brain vasculature and are thus BCECs. Seizure-induced BCECs cultured in EC media exhibited low proliferative potential and abnormal cell contacts. BCEC appearance during seizures was blocked by a CO-releasing molecule (CORM-A1) or cobalt protoporphyrin (heme oxygenase-1 inducer), which prevented apoptosis in cerebral arterioles and the loss of cerebral vascular endothelial function during the late postictal period. These findings suggest that seizure-induced BCECs are injured ECs dislodged from cerebral microvessels during seizures. The correlation between the appearance of BCECs in peripheral blood, apoptosis in cerebral vessels, and the loss of postictal cerebral vascular function suggests that BCECs are early indicators of late cerebral vascular damage. PMID- 20363896 TI - Myocardial adenosine A(1)-receptor-mediated adenoprotection involves phospholipase C, PKC-epsilon, and p38 MAPK, but not HSP27. AB - Adenosine via an adenosine A(1) receptor (A(1)R) is a negative feedback inhibitor of adrenergic stimulation in the heart, protecting it from toxic effects of overstimulation. Stimulation of the A(1)R results in the activation of G(i) protein, release of free Gbetagamma-subunits, and activation/translocation of PKC epsilon to the receptor for activated C kinase 2 protein at the Z-line of the cardiomyocyte sarcomere. Using an anti-Gbetagamma peptide, we investigated the role of these subunits in the A(1)R stimulation of phospholipase C (PLC), with the premise that the resulting diacylglycerol provides for the activation of PKC epsilon. Inositol 1,4,5-triphosphate release was an index of PLC activity. Chlorocyclopentyl adenosine (CCPA), an A(1)R agonist, increased inositol 1,4,5 triphosphate production by 273% in mouse heart homogenates, an effect absent in A(1)R knockout hearts and inhibited by anti-Gbetagamma peptide. In a second study, p38 MAPK and heat shock protein 27 (HSP27), found by others to be associated with the loss of myocardial contractile function, were postulated to play a role in the actions of A(1)R. Isoproterenol, a beta-adrenergic receptor agonist, increased the Ca(2+) transient and sarcomere shortening magnitudes by 36 and 49%, respectively. In the rat cardiomyocyte, CCPA significantly reduced these increases, an action blocked by the p38 MAPK inhibitor SB-203580. While CCPA significantly increased the phosphorylation of HSP27, this action was inhibited by isoproterenol. These data indicate that the activation of PKC-epsilon by A(1)R results from the activation of PLC via free Gbetagamma-subunits released upon A(1)R-induced dissociation of G(i)alphabetagamma. Attenuation of beta-adrenergic induced contractile function by A(1)R may involve the activation of p38 MAPK, but not HSP27. PMID- 20363897 TI - Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats. AB - A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion. Rats were randomly assigned to one of three groups: myocardial infarction (MI)-control group, 45 min ischemia followed by 24 h of reperfusion; MI-EPO group, similar surgery with a single bolus of EPO administered at the onset of reperfusion; and sham-operated group. Short-axis two-dimensional echocardiography was performed after reperfusion. Global radial (GS(r)) and circumferential (GS(cir)) strains were compared with infarct size and TEMI assessed after triphenyltetrazolium chloride staining. As a result, ejection fraction, shortening fraction, GS(r), and GS(cir) significantly correlated to infarct size, whereas only GS(r) and GS(cir) significantly correlated to TEMI. EPO significantly decreased infarct size (30.8 + or - 3.5 vs. 56.2 + or - 5.7% in MI-control, P < 0.001) and TEMI (0.37 + or - 0.05 vs. 0.77 + or - 0.05 in MI-control, P < 0.001). None of the conventional echocardiography parameters was significantly different between the MI-EPO and MI-control groups, whereas GS(r) was significantly higher in the MI EPO group (29.1 + or - 4.7 vs. 16.4 + or - 3.3% in MI-control; P < 0.05). Furthermore, GS(cir) and GS(r) appeared to be the best parameters to identify a TEMI >0.75 24 h after reperfusion. In conclusion, these findings demonstrate the usefulness of speckle tracking imaging in the early evaluation of a cardioprotective strategy in a rat model of ischemia-reperfusion. PMID- 20363898 TI - Evaluation of lysine biosynthesis as an antifungal drug target: biochemical characterization of Aspergillus fumigatus homocitrate synthase and virulence studies. AB - Aspergillus fumigatus is the main cause of severe invasive aspergillosis. To combat this life-threatening infection, only limited numbers of antifungals are available. The fungal alpha-aminoadipate pathway, which is essential for lysine biosynthesis, has been suggested as a potential antifungal drug target. Here we reanalyzed the role of this pathway for establishment of invasive aspergillosis in murine models. We selected the first pathway-specific enzyme, homocitrate synthase (HcsA), for biochemical characterization and for study of its role in virulence. A. fumigatus HcsA was specific for the substrates acetyl-coenzyme A (acetyl-CoA) and alpha-ketoglutarate, and its activity was independent of any metal ions. In contrast to the case for other homocitrate synthases, enzymatic activity was hardly affected by lysine and gene expression increased under conditions of lysine supplementation. An hcsA deletion mutant was lysine auxotrophic and unable to germinate on unhydrolyzed proteins given as a sole nutrient source. However, the addition of partially purified A. fumigatus proteases restored growth, confirming the importance of free lysine to complement auxotrophy. In contrast to lysine-auxotrophic mutants from other fungal species, the mutant grew on blood and serum, indicating the existence of high-affinity lysine uptake systems. In agreement, although the virulence of the mutant was strongly attenuated in murine models of bronchopulmonary aspergillosis, virulence was partially restored by lysine supplementation via the drinking water. Additionally, in contrast to the case for attenuated pulmonary infections, the mutant retained full virulence when injected intravenously. Therefore, we concluded that inhibition of fungal lysine biosynthesis, at least for disseminating invasive aspergillosis, does not appear to provide a suitable target for new antifungals. PMID- 20363899 TI - Single-step affinity purification for fungal proteomics. AB - A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included. PMID- 20363900 TI - Shyness and marriage: does shyness shape even established relationships? AB - Do shy people struggle to maintain their relationships just as they struggle to develop them? The current research addressed this question through one cross sectional and one longitudinal study in which recently married couples reported their levels of shyness, relationship self-efficacy, marital problem severity, and marital satisfaction. Multilevel modeling revealed that (a) shyness was negatively associated with concurrent marital satisfaction in Study 1 and with declines in marital satisfaction in Study 2, (b) the association between shyness and satisfaction was mediated by low levels of relationship self-efficacy in Study 1 and Study 2, and (c) the association between relationship self-efficacy and concurrent marital satisfaction was mediated by concurrent marital problems in Study 1, and the association between relationship self-efficacy and declines in marital satisfaction was mediated by worsening marital problems in Study 2. These findings join a growing body of research demonstrating the cognitive mechanisms through which personality shapes relationships. PMID- 20363901 TI - "Think" versus "feel" framing effects in persuasion. AB - Three studies explored think ("I think . . . ") versus feel ("I feel . . . ") message framing effects on persuasion.The authors propose a matching hypothesis, suggesting that think framing will be more persuasive when the target attitude or message recipient is cognitively oriented, whereas feel framing will be more persuasive when the target attitude or message recipient is affectively oriented. Study 1 presented cognitively and affectively oriented individuals with a think- or feel-framed message. Study 2 primed cognitive or affective orientation and then presented a think- or feel-framed message. Study 3 presented male and female participants with an advertisement containing think- or feel-framed arguments. Results indicated that think (feel) framing was more persuasive when the target attitude or recipient was cognitively (affectively) oriented. Moreover, Study 2 demonstrated that this matching effect was mediated by processing fluency. Theoretical and practical implications are discussed. PMID- 20363902 TI - Self-knowledge reduces conflict by biasing one of plural possible answers. AB - The authors investigated whether self-knowledge has a function to reduce conflict by biasing one of two choices during occupational choice (e.g., Which occupation do you think you could do better?-dancer or chemist). In the three experiments, event-related brain potentials were recorded. Experiment 1 revealed that the amplitude of the conflict-related negativity (CRN) reflects strength of conflict during occupational choice. Results of Experiment 2 demonstrated that the CRN amplitude during occupational choice was smaller when self-knowledge was activated than when other-knowledge was activated. Experiment 3 showed that the CRN amplitude during occupational choice was decreased more when self-knowledge that biases one choice of occupation was activated than when self-knowledge that does not bias was activated. These results suggest that self-knowledge reduces conflict by biasing one of multiple choices in situations where two or more possible correct answers can be given. PMID- 20363903 TI - The stingy hour: how accounting for time affects volunteering. AB - These studies examined how the practice of accounting for one's time-so that work can be billed or charged to specific clients or projects-affects the decision to allocate time to volunteer activities. Using longitudinal data collected from law students transitioning to their first jobs, Study 1 showed that exposure to billing time diminished individuals' willingness to volunteer, even after controlling for attitudes about volunteering held before entering the workforce as well as the individual's specific opportunity costs of volunteering time. Studies 2-5 experimentally manipulated billing time and confirmed its causal effect on individuals' willingness to volunteer and actual volunteering behavior. Study 5 showed that the effect of exposure to billing time on volunteering occurred above and beyond any effects on general self-efficacy or self determination. Individual differences moderated the effects of billing, such that people who did not value money as much were less affected. PMID- 20363904 TI - Can't control yourself? Monitor those bad habits. AB - What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking "don't do it," watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed. PMID- 20363905 TI - Reducing the expression of implicit stereotypes: reflexive control through implementation intentions. AB - The authors tested the effectiveness of implementation intentions as a strategy for limiting the behavioral expression of implicit stereotypes. Implementation intentions are if-then plans that link an intended response to an anticipated situational cue, thereby enabling a reflexive form of control. The authors examined whether two different types of implementation intentions could improve response accuracy on the Shooter Task, a reaction time measure of implicit stereotyping. In Study 1, participants used a distraction-inhibiting implementation intention designed to engage control over the perception of goal irrelevant stimuli (e.g., race). In Study 2, participants used a response facilitating implementation intention designed to promote goal-directed action. Across studies, implementation intentions improved accuracy, thereby limiting the behavioral expression of implicit stereotypes. Furthermore, process dissociation analyses indicated that the distraction-inhibiting implementation intention increased controlled processing while reducing automatic stereotype activation, whereas the response-facilitating implementation intention increased only controlled processing. Implications for goal strategy approaches to reducing prejudice are discussed. PMID- 20363906 TI - Who says we are bad people? The impact of criticism source and attributional content on responses to group-based criticism. AB - We investigated the interplay between the source of criticism and the attributional content of their message on behavioral responses to group-based criticism. Studies 1 and 2 revealed that outgroup critics were more effective when their criticism included internal attributions (to the ingroup's character) rather than external attributions (the ingroup's circumstances), whereas there was no effect of attributional content for ingroup critics (a significant Source x Content interaction). Study 3 explored the role of audiences in responses to outgroup criticism. The results indicated that the positive effects of internal versus external attributions were only evident when an outgroup audience was witness to participants' responses. Furthermore, these effects were mediated through concerns about the ingroup's image. Together, these patterns suggest that responses to criticism depend not just on the identity of the critic but also on what the critic says and who is watching. People may be surprisingly responsive to outgroup criticism-particularly when inaction might lead others to perceive them as "bad people." PMID- 20363907 TI - Information, perspective, and judgments about the self in face and dignity cultures. AB - People's judgments about their own moral status and well-being were made differently by those from a Dignity culture (Anglo-Americans) and by those from a Face culture (Asian Americans). Face culture participants were more influenced by information processed from a third-person (compared with first-person) perspective, with information about the self having a powerful effect only when seen through another's eyes. Thus, (a) Asian Americans felt the greatest need for moral cleansing when thinking about how others would judge their many (vs. few) transgressions, but this effect did not hold when others were not invoked, and (b) Asian Americans defined themselves as having a rich social network and worthwhile life when thinking about how others would evaluate their many (vs. few) friendships, but again, effects did not hold when others were not invoked. In contrast, Anglo-Americans responded to information about their transgressions or friendships, but effects were pronounced only when other people were not invoked. PMID- 20363908 TI - Stigmatizing materialism: on stereotypes and impressions of materialistic and experiential pursuits. AB - Five studies examined the stigmatization of materialism. Participants expressed negative stereotypes of materialistic people, considering them to be more selfish and self-centered than experiential people (Study 1). Participants also viewed materialistic pursuits as more extrinsically motivated than experiential pursuits (Study 2). These stereotypes led respondents from varied demographic backgrounds to form less favorable impressions of individuals who were associated with prototypically materialistic versus experiential purchases, a result that was statistically mediated by impressions that materialistic purchases were more extrinsically motivated (Study 3). These differential impressions are primarily attributable to the denigration of materialistic people rather than the admiration of experiential people (Study 4). The stigmatization of materialism led participants to like less and enjoy interacting less with their conversation partners when discussing materialistic rather than experiential purchases (Study 5). The authors discuss these findings' implications for self-perception, accurate social perception, and well-being. PMID- 20363909 TI - Affective regulation of stereotype activation: it's the (accessible) thought that counts. AB - Prior research has found that positive affect, compared to negative affect, increases stereotype activation. In four experiments the authors explore whether the link between affect and stereotype activation depends on the relative accessibility of stereotype-relevant thoughts and response tendencies. As well as manipulating mood, the authors measured or manipulated the accessibility of egalitarian response tendencies (Experiments 1 and 2) and counterstereotypic thoughts (Experiments 2 through 4). In the absence of such response tendencies and thoughts, people in positive moods displayed greater stereotype activation consistent with past research. By contrast, in the presence of accessible egalitarian response tendencies or counterstereotypic thoughts, people in positive moods exhibited less stereotype activation than those in negative moods. Implications of these results for existing affect-cognition models are discussed. PMID- 20363910 TI - HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. AB - Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1alpha) and endothelial PAS domain protein 1 (EPAS1; HIF-2alpha), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index > or = 30 kg/m2) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications. PMID- 20363911 TI - Overexpression of Bcl-2 in vascular endothelium inhibits the microvascular lesions of diabetic retinopathy. AB - Recent studies on the pathogenesis of diabetic retinopathy have focused on correcting adverse biochemical alterations, but there have been fewer efforts to enhance prosurvival pathways. Bcl-2 is the archetypal member of a group of antiapoptotic proteins. In this study, we investigated the ability of overexpressing Bcl-2 in vascular endothelium to protect against early stages of diabetic retinopathy. Transgenic mice overexpressing Bcl-2 regulated by the pre proendothelin promoter were generated, resulting in increased endothelial Bcl-2. Diabetes was induced with streptozotocin, and mice were sacrificed at 2 months of study to measure superoxide generation, leukostasis, and immunohistochemistry, and at 7 months to assess retinal histopathology. Diabetes of 2 months duration caused a significant decrease in expression of Bcl-2 in retina, upregulation of Bax in whole retina and isolated retinal microvessels, and increased generation of retinal superoxide and leukostasis. Seven months of diabetes caused a significant increase in the number of degenerate (acellular) capillaries in diabetic animals. Furthermore, overexpression of Bcl-2 in the vascular endothelium inhibited the diabetes-induced degeneration of retinal capillaries and aberrant superoxide generation, but had no effect on Bax expression or leukostasis. Therefore, overexpression of Bcl-2 in endothelial cells inhibits the capillary degeneration that is characteristic of the early stages of diabetic retinopathy, and this effect seems likely to involve inhibition of oxidative stress. PMID- 20363912 TI - Impaired gastric gland differentiation in Peutz-Jeghers syndrome. AB - Gastrointestinal hamartomatous polyps in the Peutz-Jeghers cancer predisposition syndrome and its mouse model (Lkb1(+/-)) are presumed to contain all cell types native to the site of their occurrence. This study aimed to explore the pathogenesis of Peutz-Jeghers syndrome polyposis by characterizing cell types and differentiation of the epithelium of gastric polyps and predisposed mucosa. Both antral and fundic polyps were characterized by a deficit of pepsinogen C expressing differentiated gland cells (antral gland, mucopeptic, and chief cells); in large fundic polyps, parietal cells were also absent. Gland cell loss was associated with an increase in precursor neck cells, an expansion of the proliferative zone, and an increase in smooth muscle alpha-actin expressing myofibroblasts in the polyp stroma. Lack of pepsinogen C-positive gland cells identified incipient polyps, and even the unaffected mucosa of young predisposed mice displayed an increase in pepsinogen C negative glands (25%; P = 0045). In addition, in small intestinal polyps, gland cell differentiation was defective, with the absence of Paneth cells. There were no signs of metaplastic differentiation in any of the tissues studied, and both the gastric and small intestinal defects were seen in Lkb1(+/-) mice, as well as polyps from patients with Peutz-Jeghers syndrome. These results identify impaired epithelial differentiation as the earliest pathological sign likely to contribute to tumorigenesis in individuals with inherited Lkb1 mutations. PMID- 20363913 TI - Loss of Nkx3.1 expression in bacterial prostatitis: a potential link between inflammation and neoplasia. AB - NKX3.1 is a homeodomain protein that functions as a dosage sensitive prostate specific transcription factor. Diminished NKX3.1 expression is associated with prostate epithelial cell proliferation in vitro and with increasing Gleason grade in patient samples. Mouse Nkx3.1 also functions as a negative regulator of prostate cell growth in prostate cancer models. Identifying biological and environmental factors that modulate NKX3.1 accumulation is therefore central to efforts aimed at elucidating prostate growth control mechanisms. To determine the effect of inflammation on Nxk3.1 accumulation, bacterial prostatitis was induced by intraurethral inoculation of a uropathogenic E. coli strain in mice. Nkx3.1 expression was profoundly reduced in infected prostate lobes and correlated with increased expression of a proliferation marker. Androgen receptor levels were also reduced in concert with Nkx3.1, and a marked increase in the basal cell marker p63 was observed. Analyses of the inflammatory infiltrate revealed a classic acute inflammatory response that attained characteristics of a chronic state within fourteen days postinoculation. Comparison of the four prostate lobes revealed clear differences in the extent of inflammation. These data demonstrate that acute inflammation in response to a bacterial agent in the prostate is associated with a significant diminution in the level of a key regulator of prostate cell proliferation. These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth. PMID- 20363914 TI - Endothelial von Willebrand factor release due to eNOS deficiency predisposes to thrombotic microangiopathy in mouse aging kidney. AB - Endothelial dysfunction is critical in the decline of renal function with. By using endothelial nitric oxide synthase knockout (eNOSKO) mice, we tested the hypothesis that a lack of endothelial nitric oxide synthase accelerates renal injury in the aging kidney. In contrast to control mice and young eNOSKO mice, aging eNOSKO mice showed greater renal injury and in particular developed a thrombotic microangiopathy, with mesangiolysis, endothelial swelling, endothelial cell loss, double-contour appearance of glomerular basement membrane (GBM), and thrombus formation. Thrombi, which were composed of fibrin, platelets, and von Willebrand factor (vWF), were identified predominantly in glomerular capillaries and rarely in arterioles, but not in larger vessels. In the tubulointerstitium, tubular degeneration and macrophage infiltration were also prominent in aging eNOSKO mice. Intraluminal vWF deposition was accompanied with thrombus formation, whereas mesangial deposition of vWF was associated with mesangial matrix expansion. Furthermore, the mesangial vWF deposition was detectable in young eNOSKO mice in which severe glomerular injury had not yet developed. Finally, a higher level of serum P-selectin in eNOSKO mice was consistent with the vWF behavior and suggested exocytosis of the Weibel-Palade body by the endothelium. In conclusion, a lack of endothelial nitric oxide synthase resulted in the development of glomerular thrombotic microangiopathy. A lack of nitric oxide likely contributed to the release of vWF, leading to thrombus formation in this model. PMID- 20363915 TI - O-fucose modulates Notch-controlled blood lineage commitment. AB - Notch receptors are cell surface molecules essential for cell fate determination. Notch signaling is subject to tight regulation at multiple levels, including the posttranslational modification of Notch receptors by O-linked fucosylation, a reaction that is catalyzed by protein O-fucosyltransferase-1 (Pofut1). Our previous studies identified a myeloproliferative phenotype in mice conditionally deficient in cellular fucosylation that is attributable to a loss of Notch dependent suppression of myelopoiesis. Here, we report that hematopoietic stem cells deficient in cellular fucosylation display decreased frequency and defective repopulating ability as well as decreased lymphoid but increased myeloid developmental potential. This phenotype may be attributed to suppressed Notch ligand binding and reduced downstream signaling of Notch activity in hematopoietic stem cells. Consistent with this finding, we further demonstrate that mouse embryonic stem cells deficient in Notch1 (Notch1(-/-)) or Pofut1 (Pofut1(-/-)) fail to generate T lymphocytes but differentiate into myeloid cells while coculturing with Notch ligand-expressing bone marrow stromal cells in vitro. Moreover, in vivo hematopoietic reconstitution of CD34(+) progenitor cells derived from either Notch1(-/-) or Pofut1(-/-) embryonic stem cells show enhanced granulopoiesis with depressed lymphoid lineage development. Together, these results indicate that Notch signaling maintains hematopoietic lineage homeostasis by promoting lymphoid development and suppressing overt myelopoiesis, in part through processes controlled by O-linked fucosylation of Notch receptors. PMID- 20363916 TI - A role for the epithelial microenvironment at tumor boundaries: evidence from Drosophila and human squamous cell carcinomas. AB - Recent work has shown an increasing appreciation for the importance of the tumor environment, most commonly the overlying stroma. Less emphasis has been placed on the importance of local communication between transformed cells and their neighbors within the epithelium at tumor boundaries. We previously reported a Drosophila model that highlighted the importance of local interactions within the epithelial microenvironment: Src-transformed cells (Csk-deficient) were influenced by their immediate normal neighbors. The result was a consistent change in 'border cells' at the edge of transformed patches including delocalized p120-catenin and E-cadherin as well as invasive migration through the basal lamina. Here we show that the invasive properties of the boundary cells depend on up-regulation of Drosophila matrix metalloproteinase-1 as assessed by promoter activity, protein levels, in situ enzymatic activity, and tests of genetic modifier activity. Further, we provide evidence that these events at tumor borders may be evolutionarily conserved. We detected changes in 'boundary cells' within histological sections of human squamous cell carcinomas that were similar to those observed in Drosophila: both E-cadherin and p120-catenin exhibited normal junctional localization at the centers of the tumors but were reduced or delocalized at the boundary. Further, matrix metalloproteinase-2 was up regulated within these same boundary cells. These results support the view that local cell cell interactions within the epithelial microenvironment impact tumor invasion and progression. PMID- 20363917 TI - Characterization of a model of an arteriovenous fistula in the rat: the effect of L-NAME. AB - Vascular access dysfunction contributes to the mortality of patients undergoing chronic hemodialysis. The present study analyzed the changes that evolve in a femoral arteriovenous fistula in the rat. The venous segment of this model exhibited, at 1 week, activation of pro-inflammatory transcription factors and up regulation of pro-inflammatory, proliferative, procoagulant, and profibrotic genes; and at 4 weeks, the venous segment displayed neointimal hyperplasia, smooth muscle proliferation, and thrombus formation. These changes were accompanied by endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS up-regulation. The administration of NG-nitro-L-arginine methyl ester, an inhibitor of NOS activity, increased venous neointimal hyperplasia and pro inflammatory gene expression (monocyte chemoattractant protein-1 and cytokine induced neutrophil chemoattractant-1), increased systolic blood pressure, and decreased blood flow through the fistula. In another hypertensive model, the rat subtotal nephrectomy model, venous neointimal hyperplasia in the arteriovenous fistula was also exacerbated. We conclude that this arteriovenous fistula model recapitulates the salient features observed in dysfunctional, hemodialysis arteriovenous fistulas, and that venous neointimal hyperplasia is exacerbated when this model is superimposed in two different models of systemic hypertension. Since the uremic milieu contains increased amounts of asymmetric dimethylarginine, we speculate that such accumulation of this endogenous inhibitor of NOS, by virtue of its pressor or nitric oxide-depleting effects, or a combination thereof, may contribute to the limited longevity of arteriovenous fistulas used for hemodialysis. PMID- 20363918 TI - Peroxisome proliferator-activated receptor (PPAR)gamma can inhibit chronic renal allograft damage. AB - Chronic inflammation and fibrosis are the leading causes of chronic allograft failure. The nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma is a transcription factor known to have antidiabetogenic and immune effects, and PPARgamma forms obligate heterodimers with the retinoid X receptor (RXR). We have reported that a retinoic acid (RAR)/RXR-agonist can potently influence the course of renal chronic allograft dysfunction. In this study, in a Fischer to Lewis rat renal transplantation model, administration of the PPARgamma agonist, rosiglitazone, independent of dose (3 or 30 mg/kgBW/day), lowered serum creatinine, albuminuria, and chronic allograft damage with a chronic vascular damage score as follows: 35.0 +/- 5.8 (controls) vs. 8.1 +/- 2.4 (low dose-Rosi; P < 0.05); chronic tubulointerstitial damage score: 13.6 +/- 1.8 (controls) vs. 2.6 +/- 0.4 (low dose-Rosi; P < 0.01). The deposition of extracellular matrix proteins (collagen, fibronectin, decorin) was strikingly lower. The expression of transforming growth factor-beta1 was inhibited, whereas that of bone morphogenic protein-7 (BMP-7) was increased. Intragraft mononuclear cells and activated fibroblast numbers were reduced by 50%. In addition, the migratory and proliferative activity of these cells was significantly inhibited in vitro. PPARgamma activation diminished the number of cells expressing the proinflammatory and fibrogenic proteoglycan biglycan. In macrophages its secretion was blocked by rosiglitazone in a predominantly PPARgamma-dependent manner. The combination of PPARgamma- and RAR/RXR-agonists resulted in additive effects in the inhibition of fibrosis. In summary, PPARgamma activation was potently immunosuppressive and antifibrotic in kidney allografts, and these effects were enhanced by a RAR/RXR-agonist. PMID- 20363919 TI - ASIP Outstanding Investigator Award Lecture. New approaches to the pathology and genetics of neurodegeneration. AB - The pathologies of major neurodegenerative diseases including Parkinson disease and Alzheimer disease have been well known for decades. More recently, advances in molecular genetics have suggested important mechanistic links between the pathology of these disorders and pathogenesis of neuronal dysfunction and death. Numerous animal models have been produced based on the new information emerging from human genetic studies. As a complement to traditional mouse models, a number of investigators have modeled neurodegenerative diseases in simple model organisms ranging from yeast to Drosophila. These simple genetic models often display remarkable pathological similarities to their cognate human disorders, and genetic and biochemical studies have yielded important insights into the pathogenesis of the human disorders. Use of these tractable simple models may become even more important as large amounts of genetic data emerge from genome wide association studies in Alzheimer disease, Parkinson disease, and other neurodegenerative disorders. PMID- 20363920 TI - Rapamycin extends maximal lifespan in cancer-prone mice. AB - Aging is associated with obesity and cancer. Calorie restriction both slows down aging and delays cancer. Evidence has emerged that the nutrient-sensing mammalian target of rapamycin (mTOR) pathway is involved in cellular and organismal aging. Here we show that the mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases lifespan, and suppresses carcinogenesis in transgenic HER-2/neu cancer-prone mice. Rapamycin dramatically delayed tumor onset as well as decreased the number of tumors per animal and tumor size. We suggest that, by slowing down organismal aging, rapamycin delays cancer. PMID- 20363921 TI - Diagnostic utility of galectin-3 in thyroid cancer. AB - Galectin-3 (Gal-3), which has received significant recent attention for its utility as a diagnostic marker for thyroid cancer, represents the most well studied molecular candidate for thyroid cancer diagnosis. Gal-3 is a protein that binds to beta-galactosidase residues on cell surface glycoproteins and has also been identified in the cytoplasmic and nuclear compartment. This marker has been implicated in regulation of normal cellular proliferation and apoptosis, as well as malignant transformation and the metastasis of cancer cells. We here present a mechanistic review of Gal-3 and its role in cancer development and progression. Gal-3 expression studies in thyroid tissue and cytologic tumor specimens and their methodological considerations are also discussed in this article. Despite great variance in their methodology, the majority of immunohistochemical studies found that Gal-3 was differentially expressed in thyroid carcinoma compared with benign and normal thyroid specimens, suggesting that Gal-3 is a good diagnostic marker for thyroid cancer. Recent studies have also demonstrated improved methodological reliability. On the other hand, Gal-3 genomic expression studies have shown inconsistent results for diagnostic utility and are not recommended. Overall, the development of Gal-3 as a diagnostic marker for thyroid cancer represents a promising avenue for future study, and its clinical application could significantly reduce the number of diagnostic thyroid operations performed for cases of indeterminant fine needle aspiration biopsy cytology, and thus positively impact the current management of thyroid nodular disease. PMID- 20363922 TI - Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer. AB - FANCD2, a pivotal protein in the Fanconi anemia and BRCA pathway/network, is monoubiquitylated in the nucleus in response to DNA damage. This study examines the subcellular location and relationship with prognostic factors and patient survival of FANCD2 in breast cancer. Antibodies to FANCD2 were used to immunocytochemically stain 16 benign and 20 malignant breast specimens as well as 314 primary breast carcinomas to assess its association with subcellular compartment and prognostic factors using Fisher's Exact test or with patient survival over 20 years using Wilcoxon-Gehan statistics. Immunoreactive FANCD2 was found in the nucleus and cytoplasm of all 16 benign tissues, but nuclear staining was lost from a significant 19/20 malignant carcinomas (P < 0.0001). Antibodies to FANCD2 stained the cytoplasm of 196 primary carcinomas, leaving 118 as negatively stained. Negative cytoplasmic staining was significantly associated with positive staining for the metastasis-inducing proteins S100A4, S100P, osteopontin, and AGR2 (P < or = 0.002). Survival of patients with FANCD2-negative carcinomas was significantly worse (P < 0.0001) than those with positively stained carcinomas, and only 4% were alive at the census date. Multivariate regression analysis identified negative staining for cytoplasmic FANCD2 as the most significant indicator of patient death (P = 0.001). Thus FANCD2's cytoplasmic loss in the primary carcinomas may allow the selection of cells overexpressing proteins that can induce metastases before surgery. PMID- 20363923 TI - Induction of diabetes in aged C57B6 mice results in severe nephropathy: an association with oxidative stress, endoplasmic reticulum stress, and inflammation. AB - Kidney aging is a slowly progressive process that is postulated to be accelerated by intervening diseases, such as diabetes, due in part to the addition of excessive stress and inflammation from the intervening disease to the underlying aging process. This hypothesis was tested by inducing diabetes with streptozotocin in 18-month-old, aging mice. After 4 months of diabetes, these mice developed severe albuminuria, elevated creatinine levels, and renal lesions including extensive apoptotic cell death, glomerulosclerosis, afferent and efferent hyalinosis, and tubulointerstitial inflammation and fibrosis. These symptoms were associated with elevated oxidative stress. The presence of endoplasmic reticulum (ER) stress in 22-month-old diabetic kidneys resulted in up regulation of C/EBP homologous protein (CHOP), which may play a role in increasing kidney lesions because CHOP-deficient proximal tubular cells were resistant to ER stress-induced cell death, and CHOP-deficient mice were protected from diabetic nephropathy. Moreover, CHOP-deficient mice did not develop albuminuria as they aged. Inflammation, another key component of progressive diabetic nephropathy, was prominent in 22-month-old diabetic kidneys. The expression of tumor-necrosis factor-alpha in 22-month-old diabetic kidneys may play a role in inflammation, ER stress, and apoptosis. Thus, diabetes may accelerate the underlying kidney aging process present in old mice. PMID- 20363924 TI - Loss of negative feedback control of nuclear factor-kappaB2 activity in lymphocytes leads to fatal lung inflammation. AB - Proteolytic processing of the nuclear factor (NF)-kappaB2 precursor protein p100 generates the active NF-kappaB2 subunit p52, which in turn transcriptionally up regulates p100 expression. p100 also functions as an IkappaB molecule capable of repressing p52 activity. The biological significance of this negative feedback control loop has yet to be demonstrated in vivo. Here we show that mice deficient in p100 but with constitutive expression of p52 in lymphocytes developed fatal lung inflammation characterized by diffuse alveolar damage with marked peribronchial fibrosis. In contrast, their littermates with only p100 deficiency or constitutive expression of p52 in lymphocytes developed mild lung inflammation with perivascular lymphocyte infiltration and had a normal life span. The fatal lung inflammation is associated with high-level induction of interferon-gamma and its inducible inflammatory chemokines, suggesting the involvement of a T-helper-1 immune response. These findings demonstrate the physiological relevance of the NF kappaB2 p100 precursor protein in limiting the potentially detrimental effects of constitutive NF-kappaB2 signaling in lymphocytes. PMID- 20363925 TI - Forced expression of methionine adenosyltransferase 1A in human hepatoma cells suppresses in vivo tumorigenicity in mice. AB - Methionine adenosyltransferase (MAT) catalyzes the synthesis of S adenosylmethionine, the principal methyl donor, and is encoded by MAT1A and MAT2A in mammals. Normal liver expresses MAT1A, which is silenced in hepatocellular carcinoma. We have shown that hepatoma cells overexpressing MAT1A grew slower, but whether this is also true in vivo remains unknown. To investigate the effect of overexpressing MAT1A on in vivo tumorigenesis, we generated stable transfectants of Huh7 cells overexpressing either MAT1A or empty vector. Real time PCR and Western blotting were used to measure expression, and BALB/c nude mice were injected subcutaneously with untransfected or Huh7 cells transfected with empty or MAT1A expression vector to establish tumors. Tumor properties such as proliferation, angiogenesis, and apoptosis were compared, and microarray analysis was performed. Huh7 cells overexpressing MAT1A had higher S adenosylmethionine levels but lower bromodeoxyuridine incorporation than control cells. Tumor growth rates and weights were lower in MAT1A transfected tumors. In addition, microvessel density and CD31 and Ki-67 staining were lower in MAT1A transfected tumors than control tumors, whereas the apoptosis index was higher in MAT1A-transfected tumors. Forced expression of MAT1A induced genes related to apoptosis and tumor suppression and lowered expression of cell growth and angiogenesis proteins. Our data demonstrate in vivo overexpression of MAT1A in liver cancer cells can suppress tumor growth. They also suggest inducing MAT1A expression might be a strategy to treat hepatocellular carcinoma. PMID- 20363926 TI - Antibody-directed myostatin inhibition improves diaphragm pathology in young but not adult dystrophic mdx mice. AB - Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle wasting and weakness, leading to premature death from respiratory and/or cardiac failure. A clinically relevant question is whether myostatin inhibition can improve function of the diaphragm, which exhibits a severe and progressive pathology comparable with that in DMD. We hypothesized that antibody-directed myostatin inhibition would improve the pathophysiology of diaphragm muscle strips from young mdx mice (when the pathology is mild) and adult mdx mice (when the pathology is quite marked). Five weeks treatment with a mouse chimera of anti human myostatin antibody (PF-354, 10 mg/kg/week) increased muscle mass (P < 0.05) and increased diaphragm median fiber cross-sectional area (CSA, P < 0.05) in young C57BL/10 and mdx mice, compared with saline-treated controls. PF-354 had no effect on specific force (sPo, maximum force normalized to muscle CSA) of diaphragm muscle strips from young C57BL/10 mice, but increased sPo by 84% (P < 0.05) in young mdx mice. In contrast, 8 weeks of PF-354 treatment did not improve muscle mass, median fiber CSA, collagen infiltration, or sPo of diaphragm muscle strips from adult mdx mice. PF-354 antibody-directed myostatin inhibition completely restored the functional capacity of diaphragm strips to control levels when treatment was initiated early, but not in the later stages of disease progression, suggesting that such therapies may only have a limited window of efficacy for DMD and related conditions. PMID- 20363927 TI - Leucobacter salsicius sp. nov., from a salt-fermented food. AB - Strain M1-8(T) was isolated from jeotgal, a Korean salt-fermented food. Cells were aerobic, non-motile, Gram-reaction-positive and rod-shaped. Colonies were cream-coloured and circular with entire margins. Strain M1-8(T) exhibited optimal growth at 25-30 degrees C and pH 7.0-8.0 and in 0-4 % (w/v) NaCl. The strain tolerated up to 10.0 mM Cr(VI). Phylogenetic analyses of 16S rRNA gene sequences indicated that strain M1-8(T) represents a novel species in the genus Leucobacter. The 16S rRNA gene sequence of M1-8(T) exhibited 98.1 % similarity to that of Leucobacter chromiireducens subsp. chromiireducens L-1(T). The new isolate was clustered with Leucobacter species on a 16S rRNA gene sequence-based phylogenetic tree. The chromosomal DNA G+C content of strain M1-8(T) was 62.8 %. Its cell-wall peptidoglycan contained 2,4-diaminobutyric acid, glutamic acid, alanine, glycine and gamma-aminobutyric acid. The major menaquinone was MK-11 and the predominant fatty acids were anteiso-C15:0 (63.6 %), anteiso-C17:0 (16.7 %) and iso-C16:0 (14.2 %). The polar lipid profile of strain M1-8(T) contained diphosphatidylglycerol and one unknown glycolipid. Significant genotypic and phenotypic differences were found between strain M1-8(T) and other Leucobacter species. These differentiating characteristics indicate that strain M1-8(T) represents a novel species of the genus Leucobacter, for which the name Leucobacter salsicius sp. nov. is proposed. The type strain is M1-8(T) (=KACC 21127(T) =JCM 16362(T)). PMID- 20363928 TI - Streptomyces caeruleatus sp. nov., with dark blue diffusible pigment. AB - An actinomycete, designated strain GIMN4.002(T), was isolated from a tomato rhizosphere soil sample in Guangzhou, China. The strain produces white aerial mycelium and dark blue diffusible pigment on Gause's synthetic agar, and microscopic observation revealed that it produces looped chains of spiny spores. Morphological and chemotaxonomic characteristics of the strain are typical of the genus Streptomyces. Melanin was produced and antibacterial activity was detected against Gram-positive micro-organisms, such as Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus. The 16S rRNA gene sequence of strain GIMN4.002(T) had highest similarity (99.4 %) to Streptomyces lincolnensis B91; however, DNA-DNA relatedness between strain GIMN4.002(T) and S. lincolnensis NBRC 13054(T) was only 32.17 %. Further, the morphological, physiological and biochemical characteristics of strain GIMN4.002(T) are distinct from S. lincolnensis and other species of the genus Streptomyces with which this strain has high 16S rRNA gene sequence similarity (98-99 %). On the basis of the physiological and molecular properties observed, it is proposed that strain GIMN4.002(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces caeruleatus sp. nov. is proposed, with GIMN4.002(T) (=CCTCC M 208213(T) =NRRL B-24802(T)) as the type strain. PMID- 20363929 TI - Chryseobacterium chaponense sp. nov., isolated from farmed Atlantic salmon (Salmo salar). AB - Two bacterial strains, designated Sa 1147-06(T) and Sa 1143-06, were isolated from Atlantic salmon (Salmo salar) farmed in Lake Chapo, Chile, and were studied using a polyphasic approach. Both isolates were very similar; cells were rod shaped, formed yellow-pigmented colonies and were Gram-reaction-negative. Based on 16S rRNA gene sequence analysis, strains Sa 1147-06(T) and Sa 1143-06 shared 100 % sequence similarity and showed 98.9 and 97.5 % sequence similarity to Chryseobacterium jeonii AT1047(T) and Chryseobacterium antarcticum AT1013(T), respectively. Sequence similarities to all other members of the genus Chryseobacterium were below 97.3 %. The major fatty acids of strain Sa 1147 06(T) were iso-C13:0, iso-C15:0, anteiso-C15:0 and iso-C17:1omega9c, with iso C15:0 3-OH, iso-C16:0 3-OH and iso-C17:0 3-OH constituting the major hydroxylated fatty acids. DNA-DNA hybridizations with C. jeonii JMSNU 14049(T) and C. antarcticum JMNSU 14040(T) gave relatedness values of 20.7 % (reciprocal 15.1 %) and 15.7 % (reciprocal 25.7 %), respectively. Together, the DNA-DNA hybridization results and differentiating biochemical properties showed that strains Sa 1147-06(T) and Sa 1143-06 represent a novel species, for which the name Chryseobacterium chaponense sp. nov. is proposed. The type strain is Sa 1147 06(T) (=DSM 23145(T) =CCM 7737(T)). PMID- 20363930 TI - Agarivorans gilvus sp. nov. isolated from seaweed. AB - A novel agarase-producing, non-endospore-forming marine bacterium, WH0801(T), was isolated from a fresh seaweed sample collected from the coast of Weihai, China. Preliminary characterization based on 16S rRNA gene sequence analysis showed that WH0801(T) shared 96.1 % similarity with Agarivorans albus MKT 106(T), the type species of the genus Agarivorans. A polyphasic taxonomic study was conducted and confirmed the phylogenetic affiliation of strain WH0801(T) to the genus Agarivorans. Isolate WH0801(T) produces light-yellow-pigmented colonies; cells are Gram-stain-negative, straight or curved rods, which are motile with a single polar flagellum. Strain WH0801(T) grew in 0.5-5 % NaCl, with optimum growth at 3 % NaCl, and its optimal pH and cultivation temperature were 8.4-8.6 and 28-32 degrees C, respectively. Data from biochemical tests, whole-cell fatty acid profiling, 16S rRNA gene sequence studies and DNA-DNA hybridization clearly indicated that isolate WH0801(T) represented a novel species within the genus Agarivorans, for which the name Agarivorans gilvus sp. nov. is proposed. The type strain of Agarivorans gilvus sp. nov. is WH0801(T) (=NRRL B-59247(T) =CGMCC 1.10131(T)). PMID- 20363931 TI - Saccharospirillum aestuarii sp. nov., isolated from tidal flat sediment, and an emended description of the genus Saccharospirillum. AB - A Gram-reaction-negative, chemoheterotrophic, non-motile, facultatively anaerobic, curved rod-shaped bacterial strain, IMCC4453(T), was isolated from tidal flat sediment and subjected to a taxonomic study using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain IMCC4453(T) belonged to the genus Saccharospirillum, forming a robust clade with members of the genus, and was most closely related to the type strains of Saccharospirillum salsuginis (97.6 % similarity) and Saccharospirillum impatiens (95.9 %). The DNA-DNA relatedness value between strain IMCC4453(T) and S. salsuginis YIM-Y25(T) was 23-30 %. Differences in several physiological and biochemical characteristics between strain IMCC4453(T) and the two recognized species of the genus Saccharospirillum, together with phylogenetic and genomic distinctiveness, differentiated the novel strain from members of the genus Saccharospirillum. On the basis of the data from the present study, it is concluded that strain IMCC4453(T) represents a novel species of the genus Saccharospirillum, for which the name Saccharospirillum aestuarii sp. nov. is proposed. The type strain is IMCC4453(T) (=KCTC 22684(T)=KCCM 42930(T)=NBRC 105825(T)). An emended description of the genus Saccharospirillum is provided. PMID- 20363932 TI - Visualization of Flagella during bacterial Swarming. AB - When cells of Escherichia coli are grown in broth and suspended at low density in a motility medium, they swim independently, exploring a homogeneous, isotropic environment. Cell trajectories and the way in which these trajectories are determined by flagellar dynamics are well understood. When cells are grown in a rich medium on agar instead, they elongate, produce more flagella, and swarm. They move in coordinated packs within a thin film of fluid, in intimate contact with one another and with two fixed surfaces, a surfactant monolayer above and an agar matrix below: they move in an inhomogeneous, anisotropic environment. Here we examine swarm-cell trajectories and ways in which these trajectories are determined by flagellar motion, visualizing the cell bodies by phase-contrast microscopy and the flagellar filaments by fluorescence microscopy. We distinguish four kinds of tracks, defining stalls, reversals, lateral movement, and forward movement. When cells are stalled at the edge of a colony, they extend their flagellar filaments outwards, moving fluid over the virgin agar; when cells reverse, changes in filament chirality play a crucial role; when cells move laterally, they are pushed sideways by adjacent cells; and when cells move forward, they are pushed by flagellar bundles in the same way as when they are swimming in bulk aqueous media. These maneuvers are described in this report. PMID- 20363933 TI - Haloferax volcanii flagella are required for motility but are not involved in PibD-dependent surface adhesion. AB - Although the genome of Haloferax volcanii contains genes (flgA1-flgA2) that encode flagellins and others that encode proteins involved in flagellar assembly, previous reports have concluded that H. volcanii is nonmotile. Contrary to these reports, we have now identified conditions under which H. volcanii is motile. Moreover, we have determined that an H. volcanii deletion mutant lacking flagellin genes is not motile. However, unlike flagella characterized in other prokaryotes, including other archaea, the H. volcanii flagella do not appear to play a significant role in surface adhesion. While flagella often play similar functional roles in bacteria and archaea, the processes involved in the biosynthesis of archaeal flagella do not resemble those involved in assembling bacterial flagella but, instead, are similar to those involved in producing bacterial type IV pili. Consistent with this observation, we have determined that, in addition to disrupting preflagellin processing, deleting pibD, which encodes the preflagellin peptidase, prevents the maturation of other H. volcanii type IV pilin-like proteins. Moreover, in addition to abolishing swimming motility, and unlike the flgA1-flgA2 deletion, deleting pibD eliminates the ability of H. volcanii to adhere to a glass surface, indicating that a nonflagellar type IV pilus-like structure plays a critical role in H. volcanii surface adhesion. PMID- 20363934 TI - The Pseudomonas aeruginosa pathogenicity island PAPI-1 is transferred via a novel type IV pilus. AB - Pseudomonas aeruginosa is a major cause of nosocomial infections, particularly in immunocompromised patients or in individuals with cystic fibrosis. The notable ability of P. aeruginosa to inhabit a broad range of environments, including humans, is in part due to its large and diverse genomic repertoire. The genomes of most strains contain a significant number of large and small genomic islands, including those carrying virulence determinants (pathogenicity islands). The pathogenicity island PAPI-1 of strain PA14 is a cluster of 115 genes, and some have been shown to be responsible for virulence phenotypes in a number of infection models. We have previously demonstrated that PAPI-1 can be transferred to other P. aeruginosa strains following excision from the chromosome of the donor. Here we show that PAPI-1 is transferred into recipient P. aeruginosa by a conjugative mechanism, via a type IV pilus, encoded in PAPI-1 by a 10-gene cluster which is closely related to the genes in the enterobacterial plasmid R64. We also demonstrate that the precursor of the major pilus subunit, PilS2, is processed by the chromosomally encoded prepillin peptidase PilD but not its paralog FppA. Our results suggest that the pathogenicity island PAPI-1 may have evolved by acquisition of a conjugation system but that because of its dependence on an essential chromosomal determinant, its transfer is restricted to P. aeruginosa or other species capable of providing a functional prepilin peptidase. PMID- 20363935 TI - Sequential XylS-CTD binding to the Pm promoter induces DNA bending prior to activation. AB - XylS protein, a member of the AraC family of transcriptional regulators, comprises a C-terminal domain (CTD) involved in DNA binding and an N-terminal domain required for effector binding and protein dimerization. In the absence of benzoate effectors, the N-terminal domain behaves as an intramolecular repressor of the DNA binding domain. To date, the poor solubility properties of the full length protein have restricted XylS analysis to genetic approaches in vivo. To characterize the molecular consequences of XylS binding to its operator, we used a recombinant XylS-CTD variant devoid of the N-terminal domain. The resulting protein was soluble and monomeric in solution and activated transcription from its cognate promoter in an effector-independent manner. XylS binding sites in the Pm promoter present an intrinsic curvature of 35 degrees centered at position -42 within the proximal site. Gel retardation and DNase footprint analysis showed XylS-CTD binding to Pm occurred sequentially: first a XylS-CTD monomer binds to the proximal site overlapping the RNA polymerase binding sequence to form complex I. This first event increased Pm bending to 50 degrees and was followed by the binding of the second monomer, which further increased the observed global curvature to 98 degrees. This generated a concomitant shift in the bending center to a region centered at position -51 when the two sites were occupied (complex II). We propose a model in which DNA structure and binding sequences strongly influence XylS binding events previous to transcription activation. PMID- 20363936 TI - Direct targets of CodY in Staphylococcus aureus. AB - More than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules, and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive responses, including virulence. PMID- 20363937 TI - Mutagenesis and functional characterization of the four domains of GlnD, a bifunctional nitrogen sensor protein. AB - GlnD is a bifunctional uridylyltransferase/uridylyl-removing enzyme (UTase/UR) and is believed to be the primary sensor of nitrogen status in the cell by sensing the level of glutamine in enteric bacteria. It plays an important role in nitrogen assimilation and metabolism by reversibly regulating the modification of P(II) protein; P(II) in turn regulates a variety of other proteins. GlnD appears to have four distinct domains: an N-terminal nucleotidyltransferase (NT) domain; a central HD domain, named after conserved histidine and aspartate residues; and two C-terminal ACT domains, named after three of the allosterically regulated enzymes in which this domain is found. Here we report the functional analysis of these domains of GlnD from Escherichia coli and Rhodospirillum rubrum. We confirm the assignment of UTase activity to the NT domain and show that the UR activity is a property specifically of the HD domain: substitutions in this domain eliminated UR activity, and a truncated protein lacking the NT domain displayed UR activity. The deletion of C-terminal ACT domains had little effect on UR activity itself but eliminated the ability of glutamine to stimulate that activity, suggesting a role for glutamine sensing by these domains. The deletion of C-terminal ACT domains also dramatically decreased UTase activity under all conditions tested, but some of these effects are due to the competition of UTase activity with unregulated UR activity in these variants. PMID- 20363938 TI - Loss of the response regulator CtrA causes pleiotropic effects on gene expression but does not affect growth phase regulation in Rhodobacter capsulatus. AB - The purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus has been extensively studied for its metabolic versatility as well as for production of a gene transfer agent called RcGTA. Production of RcGTA is highest in the stationary phase of growth and requires the response regulator protein CtrA. The CtrA protein in Caulobacter crescentus has been thoroughly studied for its role as an essential, master regulator of the cell cycle. Although the CtrA protein in R. capsulatus shares a high degree of sequence similarity with the C. crescentus protein, it is nonessential and clearly plays a different role in this bacterium. We have used transcriptomic and proteomic analyses of wild-type and ctrA mutant cultures to identify the genes dysregulated by the loss of CtrA in R. capsulatus. We have also characterized gene expression differences between the logarithmic and stationary phases of growth. Loss of CtrA has pleiotropic effects, with dysregulation of expression of approximately 6% of genes in the R. capsulatus genome. This includes all flagellar motility genes and a number of other putative regulatory proteins but does not appear to include any genes involved in the cell cycle. Quantitative proteomic data supported 88% of the CtrA transcriptome results. Phylogenetic analysis of CtrA sequences supports the hypothesis of an ancestral ctrA gene within the alphaproteobacteria, with subsequent diversification of function in the major alphaproteobacterial lineages. PMID- 20363939 TI - Structural and functional characterization of an RNase HI domain from the bifunctional protein Rv2228c from Mycobacterium tuberculosis. AB - The open reading frame Rv2228c from Mycobacterium tuberculosis is predicted to encode a protein composed of two domains, each with individual functions, annotated through sequence similarity searches. The N-terminal domain is homologous with prokaryotic and eukaryotic RNase H domains and the C-terminal domain with alpha-ribazole phosphatase (CobC). The N-terminal domain of Rv2228c (Rv2228c/N) and the full-length protein were expressed as fusions with maltose binding protein (MBP). Rv2228c/N was shown to have RNase H activity with a hybrid RNA/DNA substrate as well as double-stranded RNase activity. The full-length protein was shown to have additional CobC activity. The crystal structure of the MBP-Rv2228c/N fusion protein was solved by molecular replacement and refined at 2.25-A resolution (R = 0.182; R(free) = 0.238). The protein is monomeric in solution but associates in the crystal to form a dimer. The Rv2228c/N domain has the classic RNase H fold and catalytic machinery but lacks several surface features that play important roles in the cleavage of RNA/DNA hybrids by other RNases H. The absence of either the basic protrusion of some RNases H or the hybrid binding domain of others appears to be compensated by the C-terminal CobC domain in full-length Rv2228c. The double-stranded-RNase activity of Rv2228c/N contrasts with classical RNases H and is attributed to the absence in Rv2228c/N of a key phosphate binding pocket. PMID- 20363940 TI - A novel hydrolytic dehalogenase for the chlorinated aromatic compound chlorothalonil. AB - Dehalogenases play key roles in the detoxification of halogenated aromatics. Interestingly, only one hydrolytic dehalogenase for halogenated aromatics, 4 chlorobenzoyl-coenzyme A (CoA) dehalogenase, has been reported. Here, we characterize another novel hydrolytic dehalogenase for a halogenated aromatic compound from the 2,4,5,6-tetrachloroisophthalonitrile (chlorothalonil)-degrading strain of Pseudomonas sp. CTN-3, which we have named Chd. Chd catalyzes a hydroxyl substitution at the 4-chlorine atom of chlorothalonil. The metabolite of the Chd dehalogenation, 4-hydroxy-trichloroisophthalonitrile, was identified by reverse-phase high-performance liquid chromatography (HPLC), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR). Chd dehalogenates chlorothalonil under anaerobic and aerobic conditions and does not require the presence of cofactors such as CoA and ATP. Chd contains a putative conserved domain of the metallo-beta-lactamase superfamily and shows the highest identity with several metallohydrolases (24 to 29%). Chd is a monomer (36 kDa), and the isoelectric point (pI) of Chd is estimated to be 4.13. Chd has a dissociation constant (K(m)) of 0.112 mM and an overall catalytic rate (k(cat)) of 207 s(-1) for chlorothalonil. Chd is completely inhibited by 1,10-phenanthroline, diethyl pyrocarbonate, and N-bromosuccinic acid. Site-directed mutagenesis of Chd revealed that histidines 128 and 157, serine 126, aspartates 45, 130 and 184, and tryptophan 241 were essential for the dehalogenase activity. Chd differs from other reported hydrolytic dehalogenases based on the analysis of amino acid sequences and catalytic mechanisms. This study provides an excellent dehalogenase candidate for mechanistic study of hydrolytic dehalogenation of halogenated aromatic compound. PMID- 20363941 TI - Cultivation and genomic, nutritional, and lipid biomarker characterization of Roseiflexus strains closely related to predominant in situ populations inhabiting Yellowstone hot spring microbial mats. AB - Roseiflexus sp. strains were cultivated from a microbial mat of an alkaline siliceous hot spring in Yellowstone National Park. These strains are closely related to predominant filamentous anoxygenic phototrophs found in the mat, as judged by the similarity of small-subunit rRNA, lipid distributions, and genomic and metagenomic sequences. Like a Japanese isolate, R. castenholzii, the Yellowstone isolates contain bacteriochlorophyll a, but not bacteriochlorophyll c or chlorosomes, and grow photoheterotrophically or chemoheterotrophically under dark aerobic conditions. The genome of one isolate, Roseiflexus sp. strain RS1, contains genes necessary to support these metabolisms. This genome also contains genes encoding the 3-hydroxypropionate pathway for CO(2) fixation and a hydrogenase, which might enable photoautotrophic metabolism, even though neither isolate could be grown photoautotrophically with H(2) or H(2)S as a possible electron donor. The isolates exhibit temperature, pH, and sulfide preferences typical of their habitat. Lipids produced by these isolates matched much better with mat lipids than do lipids produced by R. castenholzii or Chloroflexus isolates. PMID- 20363942 TI - A deficiency in arabinogalactan biosynthesis affects Corynebacterium glutamicum mycolate outer membrane stability. AB - Corynebacterineae is a specific suborder of Gram-positive bacteria that includes Mycobacterium tuberculosis and Corynebacterium glutamicum. The ultrastructure of the cell envelope is very atypical. It is composed of a heteropolymer of peptidoglycan and arabinogalactan (AG) covalently associated to an outer membrane. Five arabinosyltransferases are involved in the biosynthesis of AG in C. glutamicum. AftB catalyzes the transfer of Araf (arabinofuranosyl) onto the arabinan domain of the arabinogalactan to form terminal beta(1 --> 2)-linked Araf residues. Here we show that Delta aftB cells lack half of the arabinogalactan mycoloylation sites but are still able to assemble an outer membrane. In addition, we show that a Delta aftB mutant grown on a rich medium has a perturbed cell envelope and sheds a significant amount of membrane fragments in the external culture medium. These fragments contain mono- and dimycolate of trehalose and PorA/H, the major porin of C. glutamicum, but lack conventional phospholipids that typify the plasma membrane, suggesting that they are derived from the atypical mycolate outer membrane of the cell envelope. This is the first report of outer membrane destabilization in the Corynebacterineae, and it suggests that a strong interaction between the mycolate outer membrane and the underlying polymer is essential for cell envelope integrity. The presence of outer membrane-derived fragments (OMFs) in the external medium of the Delta aftB mutant is also a very promising tool for outer membrane characterization. Indeed, fingerprint analysis of major OMF-associated proteins has already led to the identification of 3 associated mycoloyltransferases and an unknown protein with a C-terminal hydrophobic anchoring domain reminiscent of that found for the S-layer protein PS2 of C. glutamicum. PMID- 20363943 TI - Glucose metabolism in Legionella pneumophila: dependence on the Entner-Doudoroff pathway and connection with intracellular bacterial growth. AB - Glucose metabolism in Legionella pneumophila was studied by focusing on the Entner-Doudoroff (ED) pathway with a combined genetic and biochemical approach. The bacterium utilized exogenous glucose for synthesis of acid-insoluble cell components but manifested no discernible increase in the growth rate. Assays with permeabilized cell preparations revealed the activities of three enzymes involved in the pathway, i.e., glucokinase, phosphogluconate dehydratase, and 2-dehydro-3 deoxy-phosphogluconate aldolase, presumed to be encoded by the glk, edd, and eda genes, respectively. Gene-disrupted mutants for the three genes and the ywtG gene encoding a putative sugar transporter were devoid of the ability to metabolize exogenous glucose, indicating that the pathway is almost exclusively responsible for glucose metabolism and that the ywtG gene product is the glucose transporter. It was also established that these four genes formed part of an operon in which the gene order was edd-glk-eda-ywtG, as predicted by genomic information. Intriguingly, while the mutants exhibited no appreciable change in growth characteristics in vitro, they were defective in multiplication within eukaryotic cells, strongly indicating that the ED pathway must be functional for the intracellular growth of the bacterium to occur. Curiously, while the deficient glucose metabolism of the ywtG mutant was successfully complemented by the ywtG(+) gene supplied in trans via plasmid, its defect in intracellular growth was not. However, the latter defect was also manifested in wild-type cells when a plasmid carrying the mutant ywtG gene was introduced. This phenomenon, resembling so-called dominant negativity, awaits further investigation. PMID- 20363945 TI - Functional dissection of the conjugative coupling protein TrwB. AB - The conjugative coupling protein TrwB is responsible for connecting the relaxosome to the type IV secretion system during conjugative DNA transfer of plasmid R388. It is directly involved in transport of the relaxase TrwC, and it displays an ATPase activity probably involved in DNA pumping. We designed a conjugation assay in which the frequency of DNA transfer is directly proportional to the amount of TrwB. A collection of point mutants was constructed in the TrwB cytoplasmic domain on the basis of the crystal structure of TrwB Delta N70, targeting the nucleotide triphosphate (NTP)-binding region, the cytoplasmic surface, or the internal channel in the hexamer. An additional set of transfer deficient mutants was obtained by random mutagenesis. Most mutants were impaired in both DNA and protein transport. We found that the integrity of the nucleotide binding domain is absolutely required for TrwB function, which is also involved in monomer-monomer interactions. Polar residues surrounding the entrance and inside the internal channel were important for TrwB function and may be involved in interactions with the relaxosomal components. Finally, the N-terminal transmembrane domain of TrwB was subjected to random mutagenesis followed by a two-hybrid screen for mutants showing enhanced protein-protein interactions with the related TrwE protein of Bartonella tribocorum. Several point mutants were obtained with mutations in the transmembranal helices: specifically, one proline from each protein may be the key residue involved in the interaction of the coupling protein with the type IV secretion apparatus. PMID- 20363944 TI - Biochemical characterization of the C4-dicarboxylate transporter DctA from Bacillus subtilis. AB - Bacterial secondary transporters of the DctA family mediate ion-coupled uptake of C(4)-dicarboxylates. Here, we have expressed the DctA homologue from Bacillus subtilis in the Gram-positive bacterium Lactococcus lactis. Transport of dicarboxylates in vitro in isolated membrane vesicles was assayed. We determined the substrate specificity, the type of cotransported ions, the electrogenic nature of transport, and the pH and temperature dependence patterns. DctA was found to catalyze proton-coupled symport of the four C(4)-dicarboxylates from the Krebs cycle (succinate, fumurate, malate, and oxaloacetate) but not of other mono and dicarboxylates. Because (i) succinate-proton symport was electrogenic (stimulated by an internal negative membrane potential) and (ii) the divalent anionic form of succinate was recognized by DctA, at least three protons must be cotransported with succinate. The results were interpreted in the light of the crystal structure of the homologous aspartate transporter Glt(Ph) from Pyrococcus horikoshii. PMID- 20363946 TI - The LysR-type nitrogen assimilation control protein forms complexes with both long and short DNA binding sites in the absence of coeffectors. AB - Most LysR-type transcriptional regulators (LTTRs) function as tetramers when regulating gene expression. The nitrogen assimilation control protein (NAC) generally functions as a dimer when binding to DNA and activating transcription. However, at some sites, NAC binds as a tetramer. Like many LTTRs, NAC tetramers can recognize sites with long footprints (74 bp for the site at nac) with a substantial DNA bend or short footprints (56 bp for the site at cod) with less DNA bending. However, unlike other LTTRs, NAC can recognize both types of sites in the absence of physiologically relevant coeffectors, suggesting that the two conformers of the NAC tetramer (extended and compact) are interchangeable without the need for any modification to induce or stabilize the change. In order for NAC to bind as a tetramer, three interactions must exist: an interaction between the two NAC dimers and an interaction between each NAC dimer and its corresponding binding site. The interaction between one dimer and its DNA site can be weak (recognizing a half-site rather than a full dimer-binding site), but the other two interactions must be strong. Since the conformation of the NAC tetramer (extended or compact) is determined by the nature of the DNA site without the intervention of a small molecule, we argue that the coeffector that determines the conformation of the NAC tetramer is the DNA site to which it binds. PMID- 20363947 TI - Genome sequence of Lentisphaera araneosa HTCC2155T, the type species of the order Lentisphaerales in the phylum Lentisphaerae. AB - Information on the genome content of deeply branching phyla with very few cultured members is invaluable for expanding understanding of microbial evolution. Lentisphaera araneosa HTCC2155(T) was isolated from the Oregon coast using dilution-to-extinction culturing. It is a marine heterotroph found in surface and mesopelagic waters in both the Pacific and Atlantic oceans and has the unusual property of producing a net-like matrix of secreted exopolysaccharide. Here we present the genome sequence of L. araneosa HTCC2155(T), importantly, one of only two sequenced members of the phylum Lentisphaerae. PMID- 20363948 TI - Genetic, structural, and antigenic analyses of glycan diversity in the O-linked protein glycosylation systems of human Neisseria species. AB - Bacterial capsular polysaccharides and lipopolysaccharides are well-established ligands of innate and adaptive immune effectors and often exhibit structural and antigenic variability. Although many surface-localized glycoproteins have been identified in bacterial pathogens and symbionts, it not clear if and how selection impacts associated glycoform structure. Here, a systematic approach was devised to correlate gene repertoire with protein-associated glycoform structure in Neisseria species important to human health and disease. By manipulating the protein glycosylation (pgl) gene content and assessing the glycan structure by mass spectrometry and reactivity with monoclonal antibodies, it was established that protein-associated glycans are antigenically variable and that at least nine distinct glycoforms can be expressed in vitro. These studies also revealed that in addition to Neisseria gonorrhoeae strain N400, one other gonococcal strain and isolates of Neisseria meningitidis and Neisseria lactamica exhibit broad-spectrum O-linked protein glycosylation. Although a strong correlation between pgl gene content, glycoform expression, and serological profile was observed, there were significant exceptions, particularly with regard to levels of microheterogeneity. This work provides a technological platform for molecular serotyping of neisserial protein glycans and for elucidating pgl gene evolution. PMID- 20363949 TI - BacA is essential for bacteroid development in nodules of galegoid, but not phaseoloid, legumes. AB - BacA is an integral membrane protein, the mutation of which leads to increased resistance to the antimicrobial peptides bleomycin and Bac7(1-35) and a greater sensitivity to SDS and vancomycin in Rhizobium leguminosarum bv. viciae, R. leguminosarum bv. phaseoli, and Rhizobium etli. The growth of Rhizobium strains on dicarboxylates as a sole carbon source was impaired in bacA mutants but was overcome by elevating the calcium level. While bacA mutants elicited indeterminate nodule formation on peas, which belong to the galegoid tribe of legumes, bacteria lysed after release from infection threads and mature bacteroids were not formed. Microarray analysis revealed almost no change in a bacA mutant of R. leguminosarum bv. viciae in free-living culture. In contrast, 45 genes were more-than 3-fold upregulated in a bacA mutant isolated from pea nodules. Almost half of these genes code for cell membrane components, suggesting that BacA is crucial to alterations that occur in the cell envelope during bacteroid development. In stark contrast, bacA mutants of R. leguminosarum bv. phaseoli and R. etli elicited the formation of normal determinate nodules on their bean host, which belongs to the phaseoloid tribe of legumes. Bacteroids from these nodules were indistinguishable from the wild type in morphology and nitrogen fixation. Thus, while bacA mutants of bacteria that infect galegoid or phaseoloid legumes have similar phenotypes in free-living culture, BacA is essential only for bacteroid development in indeterminate galegoid nodules. PMID- 20363950 TI - Selective depletion of Sulfolobus solfataricus transcription factor E under heat shock conditions. AB - Archaeal transcriptional machinery is similar to that of eukaryotes. We studied the fates of various components of the Sulfolobus solfataricus transcriptional apparatus under different stresses and found that in cells incubated at 90 degrees C for 1 h, transcription factor E (TFE) is selectively depleted, but its mRNA levels are increased. We discuss the implications of these findings. PMID- 20363952 TI - Metabolism and disposition of [14C]BMS-690514 after oral administration to rats, rabbits, and dogs. AB - (3R,4R)-4-Amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f] [1,2,4]triazin-5 yl)methyl)-3-piperidinol (BMS-690514) is a potent inhibitor of human epidermal growth factor receptors 1, 2, and 4 and vascular endothelial growth factor receptors 1 through 3. BMS-690514 is an oral oncologic agent currently being developed for the treatment of patients with advanced non-small cell lung cancer and breast cancer. In this investigation, a series of studies was conducted to determine the biotransformation of [(14)C]BMS-690514 after oral administration to rats, rabbits, and dogs. After administration of a single oral dose of [(14)C]BMS 690514 to rats and dogs, the majority of the radioactive dose (61-71%) was recovered in the feces, whereas 18 to 20% was eliminated in urine. In bile duct cannulated rats, 83 and 17% of the administered radioactivity was recovered in the bile and urine, respectively, suggesting that biliary secretion was a major route for the elimination of BMS-690514-derived radioactivity in rats. The parent compound underwent extensive metabolism in both species, with <12% of the administered radioactivity recovered as BMS-690514 in the excreta samples. Metabolite profiles in plasma were qualitatively similar in rats, rabbits, and dogs. Unchanged BMS-690514 was a prominent drug-related component in the plasma profiles from all the species. However, multiple metabolites contributed significantly to the circulating radioactivity, particularly for rabbit and dog, in which metabolites comprised 73 to 93% of the area under the time curve (0-8 h). Circulating metabolites included M6, a direct O-glucuronide conjugate; M1, a hydroxylated metabolite; and glucuronide conjugates of hydroxylated and O demethylated metabolites. Overall, the results from these studies suggested that BMS-690514 was well absorbed and highly metabolized through multiple pathways in these preclinical species. PMID- 20363953 TI - Another nightmare after SARS: knowledge perceptions of and overcoming strategies for H1N1 influenza among chronic renal disease patients in Hong Kong. AB - In this article I demonstrate the knowledge perceptions of and the preventive health behaviors toward the influenza A H1N1 pandemic, or "human swine flu," among the chronic renal disease patients in Hong Kong. Based on ethnographic data from participant observation in a chronic renal disease patient self-help alliance and semistructured interviews with its 30 members, I demonstrate that the participants' knowledge perceptions of and the adoption of the preventive health behaviors against H1N1 were greatly influenced by their past experiences of being stigmatized in the 2003 severe acute respiratory syndrome (SARS) outbreak. In addition, the past experiences in the SARS outbreak not only led the participants to remember their stigmatization experiences in this H1N1 pandemic, but also aroused the memory of the general Hong Kong population that chronic renal disease patients were "dangerous" and "polluted," which could further contribute to their stigmatization in this H1N1 pandemic. PMID- 20363951 TI - Multiple interaction domains in FtsL, a protein component of the widely conserved bacterial FtsLBQ cell division complex. AB - A bioinformatic analysis of nearly 400 genomes indicates that the overwhelming majority of bacteria possess homologs of the Escherichia coli proteins FtsL, FtsB, and FtsQ, three proteins essential for cell division in that bacterium. These three bitopic membrane proteins form a subcomplex in vivo, independent of the other cell division proteins. Here we analyze the domains of E. coli FtsL that are involved in the interaction with other cell division proteins and important for the assembly of the divisome. We show that FtsL, as we have found previously with FtsB, packs an enormous amount of information in its sequence for interactions with proteins upstream and downstream in the assembly pathway. Given their size, it is likely that the sole function of the complex of these two proteins is to act as a scaffold for divisome assembly. PMID- 20363954 TI - How boys become dogs: stigmatization and marginalization of uninitiated xhosa males in East London, South Africa. AB - Male circumcision is practiced in South Africa among the Xhosa people as a rite of passage from boyhood to manhood. The manhood status achieved after the ritual accords men power and authority in the community over women and uncircumcised men. Therefore, uninitiated men experience great pressures to get circumcised. We describe the experience of newly initiated Xhosa men in East London, South Africa. Interpretive phenomenology was used as the inquiry of choice. Data were collected through focus group discussions in which 14 men participated. The theme of marginalization of uninitiated Xhosa males emerged with two categories: (a) rejection, and (b) lack of respect. The participants revealed that uninitiated men are rejected by the community, their own families, friends, and women. We frame the discussion around the concept of stigma. Acknowledging that uninitiated males are stigmatized can help mitigate stigma, and in turn, the incidence of medical complications from botched circumcisions. PMID- 20363955 TI - Understanding men's perceptions of risks and rewards in a date rape scenario. AB - Existing research on date rape has identified important correlations between rape supportive attitudes and sexual aggression. What remains unclear is the mechanism by which these attitudes are translated into sexually aggressive behavior. This study borrows from a rational choice framework to explore the relationship between attitudes, perceptions of the risks and rewards of engaging in date rape, and self-reported hypothetical aggression in a date rape scenario. Results suggest that rape-supportive attitudes are related to particular patterns of identified risks and rewards of date rape as well as to the self-reported likelihood of engaging in date rape behavior. This supports a perspective that certain attitude structures may alter the risks and rewards that potential offenders consider in deciding whether or not to engage in sexual aggression. Implications for future research and prevention programs are discussed. PMID- 20363956 TI - Arbitrary arbitration: diverting juveniles into the justice system--a reexamination after 22 years. AB - This article reports on a study of a juvenile diversion program based in California. It replicates a similar 1986 study of a Florida-based juvenile diversion program. Both studies examine the appropriateness of the actual juvenile population serviced in comparison with the declared and described programs' target populations. Findings in the current research support earlier findings that the diversion program services self-serving, low-risk populations, rather than their intended "first-time nonviolent," more seriously at risk of continued delinquent behavior, target population. This finding is examined in terms of its relationship to issues of labeling and net widening, and suggests how the current study diversion program manages to create a facade that more seriously at-risk youth are being properly targeted by the program. PMID- 20363957 TI - Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans. AB - The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movie's final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal neocortical crosstalk persists during off-line periods after learning. PMID- 20363958 TI - Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. AB - We deeply sampled the organismal, genetic, and transcriptional diversity in fecal samples collected from a monozygotic (MZ) twin pair and compared the results to 1,095 communities from the gut and other body habitats of related and unrelated individuals. Using a new scheme for noise reduction in pyrosequencing data, we estimated the total diversity of species-level bacterial phylotypes in the 1.2 1.5 million bacterial 16S rRNA reads obtained from each deeply sampled cotwin to be approximately 800 (35.9%, 49.1% detected in both). A combined 1.1 million read 16S rRNA dataset representing 281 shallowly sequenced fecal samples from 54 twin pairs and their mothers contained an estimated 4,018 species-level phylotypes, with each sample having a unique species assemblage (53.4 +/- 0.6% and 50.3 +/- 0.5% overlap with the deeply sampled cotwins). Of the 134 phylotypes with a relative abundance of >0.1% in the combined dataset, only 37 appeared in >50% of the samples, with one phylotype in the Lachnospiraceae family present in 99%. Nongut communities had significantly reduced overlap with the deeply sequenced twins' fecal microbiota (18.3 +/- 0.3%, 15.3 +/- 0.3%). The MZ cotwins' fecal DNA was deeply sequenced (3.8-6.3 Gbp/sample) and assembled reads were assigned to 25 genus-level phylogenetic bins. Only 17% of the genes in these bins were shared between the cotwins. Bins exhibited differences in their degree of sequence variation, gene content including the repertoire of carbohydrate active enzymes present within and between twins (e.g., predicted cellulases, dockerins), and transcriptional activities. These results provide an expanded perspective about features that make each of us unique life forms and directions for future characterization of our gut ecosystems. PMID- 20363959 TI - Floral symmetry genes and the origin and maintenance of zygomorphy in a plant pollinator mutualism. AB - The evolution of floral zygomorphy is an important innovation in flowering plants and is thought to arise principally from specialization on various insect pollinators. Floral morphology of neotropical Malpighiaceae is distinctive and highly conserved, especially with regard to symmetry, and is thought to be caused by selection by its oil-bee pollinators. We sought to characterize the genetic basis of floral zygomorphy in Malpighiaceae by investigating CYCLOIDEA2-like (CYC2-like) genes, which are required for establishing symmetry in diverse core eudicots. We identified two copies of CYC2-like genes in Malpighiaceae, which resulted from a gene duplication in the common ancestor of the family. A likely role for these loci in the development of floral zygomorphy in Malpighiaceae is demonstrated by the conserved pattern of dorsal gene expression in two distantly related neotropical species, Byrsonima crassifolia and Janusia guaranitica. Further evidence for this function is observed in a Malpighiaceae species that has moved to the paleotropics and experienced coincident shifts in pollinators, floral symmetry, and CYC2-like gene expression. The dorsal expression pat-tern observed in Malpighiaceae contrasts dramatically with their actinomorphic flowered relatives, Centroplacaceae (Bhesa paniculata) and Elatinaceae (Bergia texana). In particular, B. texana exhibits a previously undescribed pattern of uniform CYC2 expression, suggesting that CYC2 expression among the actinomorphic ancestors of zygomorphic lineages may be much more complex than previously thought. We consider three evolutionary models that may have given rise to this patterning, including the hypothesis that floral zygomorphy in Malpighiaceae arose earlier than standard morphology-based character reconstructions suggest. PMID- 20363960 TI - His-tags lighten up and lose their inhibitions. PMID- 20363961 TI - Water-independent effects of dietary restriction in Drosophila. PMID- 20363962 TI - Anterior sacral pyocele with meningitis: a rare presentation of occult spinal dysraphism with congenital dermal sinus. AB - The authors describe an interesting case of a hitherto asymptomatic occult spinal defect with a congenital sacral dermal sinus which proved to be the entry point for bacterial meningitis in an otherwise healthy 9-year-old female child. The patient presented with fever and neck stiffness, and a dermal sinus in the lumbosacral region was identified on examination. Cerebrospinal fluid analysis confirmed bacterial meningitis and a spinal magnetic resonance imaging scan revealed a dermal sinus tract with an anterior spinal meningocele, caudal regression syndrome, and a tethered spinal cord. In addition to administration of intravenous antimicrobial agents, surgical exploration of the sacral dermal sinus tract was performed and an anterior sacral pyocele was drained. The pyocele cavity was disconnected from the thecal sac, and the thickened and fatty filum terminale was sectioned. Although congenital sacral dermal sinus manifesting as bacterial meningitis is known, the occurrence of an anterior sacral pyocele has not yet been described in children. PMID- 20363963 TI - Hyperperfusion on magnetic resonance imaging in acute chemotherapy-related leukoencephalopathy. AB - Acute chemotherapy-related leukoencephalopathy can present similar to acute stroke with symptoms including aphasia, dysarthria, and hemiplegia. Differentiation based on clinical appearance is challenging, and physicians must distinguish between the 2 conditions rapidly to institute appropriate therapies. An 8-year-old male with acute lymphoblastic leukemia receiving chemotherapy, including intrathecal methotrexate, presented to our emergency center with 2 hours of expressive aphasia and flaccid right hemiplegia. Emergent magnetic resonance imaging (MRI) was obtained, demonstrating diffusion restriction within bilateral corona radiata and centrum semiovale. Magnetic resonance perfusion revealed mildly increased perfusion, a finding inconsistent with ischemic stroke and previously unreported in acute chemotherapy-related leukoencephalopathy without necrosis. This increased perfusion conclusively eliminated stroke from the clinical differential. Magnetic resonance perfusion imaging proved valuable to rapidly distinguish acute chemotherapy-related leukoencephalopathy from ischemia, and the evaluation of perfusion alterations in this disorder may provide further insight into the pathophysiology of this entity. PMID- 20363964 TI - Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements. AB - CD1d-expressing cells present lipid Ag to CD1d-restricted NKT cells, which play an important role in immune regulation and tumor rejection. Lymphoid enhancer binding factor-1 (LEF-1) is one of the regulators of the Wnt signaling pathway, which is a powerful regulator in cellular growth, differentiation, and transformation. There is little evidence connecting Wnt signaling to CD1d expression. In this study, we have identified LEF-1 as a regulator of the expression of the gene encoding the human CD1d molecule (CD1D). We found that LEF 1 binds specifically to the CD1D promoter. Overexpression of LEF-1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts, whereas knockdown of LEF-1 using LEF-1-specific small interfering RNA increases CD1D transcripts in K562 and Jurkat cells but there are different levels of surface CD1d on these two cell types. Chromatin immunoprecipitation showed that the endogenous LEF-1 is situated at the CD1D promoter and interacts with histone deacetylase-1 to facilitate the transcriptional repressor activity. Knockdown of LEF-1 using small interfering RNA potentiates an acetylation state of histone H3/H4, supporting the notion that LEF-1 acts as a transcriptional repressor for the CD1D gene. Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of the human CD1D gene. PMID- 20363965 TI - Keratinocyte-associated B7-H1 directly regulates cutaneous effector CD8+ T cell responses. AB - Keratinocytes (KCs) may play important roles for maintenance of peripheral tolerance in the upper layers of the skin. Coinhibitory signals mediated via the programmed death (PD)-1 and its ligand B7-H1 (PD-L1/CD274) are crucial for the downregulation of T cell immune responses and for the maintenance of peripheral tolerance. In this study, to investigate the role of KC-expressed B7-H1 in the regulation of T cell immune responses, we generated transgenic (tg) mice overexpressing B7-H1 under the control of keratin 14 (K14) promoter (K14-B7-H1 tg). K14-B7-H1 tg mice displayed impaired contact hypersensitivity (CH) responses to primary and secondary hapten challenges. The K14-B7-H1 tg mice did not exhibit substantial impairment of cutaneous dendritic cell migration after sensitization and of hapten-specific proliferation and IFN-gamma production of CD4(+) and CD8(+) T cells in the draining lymph nodes, suggesting that overexpression of B7 H1 on KCs did not affect the induction phase of the CH response. The systemic or s.c. injection of hapten-sensitized T cells into the K14-B7-H1 tg mice did not efficiently induce the CH response. IFN-gamma expression and apoptosis of KCs in the challenged ears were impaired in K14-B7-H1 tg mice. IFN-gamma production by presensitized CD8(+) T cells stimulated with hapten-pulsed KCs was markedly impaired for the KCs obtained from the K14-B7-H1 tg mice but was restored by the addition of an anti-B7-H1 mAb. These results suggest that KC-associated B7-H1 directly downregulates the effector function of CD8(+) T cells by associating with PD-1 at local inflammatory sites and that it plays a role in peripheral T cell tolerance against exogenous Ags. PMID- 20363966 TI - PU.1 binds to a distal regulatory element that is necessary for B cell-specific expression of CIITA. AB - The transcriptional coactivator CIITA regulates MHC class II genes. In the mouse, CIITA is expressed from three distinct promoters (pI, pIII, and pIV) in a developmental and cell type-specific manner with pIII being responsible for B lymphocyte-specific expression. Although the promoter proximal sequences that regulate CIITA in B cells have been described, nothing is known about additional distal elements that may regulate its expression in B cells. Sequence homology comparisons, DNase I hypersensitivity assays, and histone modification analysis revealed a potential regulatory element located 11 kb upstream of pIII. Deletion of this element, termed hypersensitive site 1 (HSS1), in a bacterial artificial chromosome encoding the entire CIITA locus and surrounding genes, resulted in a complete loss of CIITA expression from the bacterial artificial chromosome following transfection into B cells. HSS1 and pIII displayed open chromatin architecture features in B cell but not in plasma cell lines, which are silenced for CIITA expression. PU.1 was found to bind HSS1 and pIII in B cells but not in plasma cells. Depletion of PU.1 by short hairpin RNA reduced CIITA expression. Chromatin conformation capture assays showed that HSS1 interacted directly with pIII in B cells and that PU.1 was important for this interaction. These results provide evidence that HSS1 is required for B cell-specific expression of CIITA and that HSS1 functions by interacting with pIII, forming a long-distance chromatin loop that is partly mediated through PU.1. PMID- 20363967 TI - SHIP influences signals from CD48 and MHC class I ligands that regulate NK cell homeostasis, effector function, and repertoire formation. AB - Previously, we showed that 2B4 is a dominant inhibitory receptor in SHIP deficient NK cells that prevents efficient cytolysis of complex targets. We show in this study that 2B4 deficiency restores homeostatic control and cytolytic function to SHIP-deficient NK cells. However, 2B4(-/-)SHIP(-/-) NK cells still exhibit a profound disruption of their NK receptor repertoire and are compromised for induction of IFN-gamma by several NK-activating receptors, including NKp46, NK.1.1, and NKG2D. In addition, we find that 2B4(-/-) NK cells have an extensively disrupted repertoire, including a supernormal frequency of NKp46(+) NK cells. Consequently IFN-gamma is induced on a much higher percentage of 2B4(-/ ) NK cells following engagement of NKp46. We also find that both SHIP and 2B4 are required to prevent expression of Ly49B, a myeloid lineage MHC class I receptor not normally expressed by the NK lineage. Finally, when SHIP-deficient NK cells are on an H-2(d) background, they exhibit supernormal levels of Ly49A and possess normal cytolytic function against MHC-matched tumor targets and enhanced cytolysis of MHC mismatched tumor targets. However, despite normal or elevated cytolytic function, H2d SHIP(-/-) NK cells exhibit poor induction of IFN-gamma like their H2b(+) or 2B4(-/-) counterparts, demonstrating a uniform requirement for SHIP in induction of IFN-gamma downstream of key NK activating receptors. These findings reveal a complex interplay of SHIP, 2B4, and MHC in the regulation of homeostasis, effector function, and repertoire formation in the NK cell lineage. PMID- 20363968 TI - Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes. AB - IL-17-producing T cells are regarded as potential pathogenic T cells in the induction of autoimmune diseases. Previously, we have shown that injection of adjuvants containing Mycobacterium, such as CFA or bacillus Calmette-Guerin, can prevent type 1 diabetes in NOD mice. We injected NOD mice with mycobacterial products s.c. and analyzed the IL-17-producing cells from the draining lymph nodes and spleen by restimulating whole-cell populations or CD4(+) T cells in vitro with or without IL-17-polarizing cytokines. Mice receiving CFA had a concomitant rise in the level of IL-17, IL-22, IL-10, and IFN-gamma in the draining lymph node and spleen. Adoptive transfer of splenocytes from CFA injected NOD mice polarized with TGF-beta plus IL-6 or IL-23 delayed the development of diabetes in recipient mice. IL-17-producing cells induced by CFA maintained their IL-17-producing ability in the recipient mice. Injection of CFA also changed the cytokine profile of cells in pancreatic tissue by increasing IL 17, IL-10, and IFN-gamma cytokine gene expression. We suggest that the rise in the level of IL-17 after adjuvant therapy in NOD mice has a protective effect on type 1 diabetes development. PMID- 20363969 TI - Intercellular adhesion molecule-1 enrichment near tricellular endothelial junctions is preferentially associated with leukocyte transmigration and signals for reorganization of these junctions to accommodate leukocyte passage. AB - Leukocyte transmigration occurs at specific locations (portals) on the endothelium, but the nature of these portals is not clear. Using intravital confocal microscopy of anesthetized mouse cremaster muscle in combination with immunofluorescence labeling, we showed that in microvessels transmigration is mainly junctional and preferentially occurs at tricellular endothelial junctional regions. Our data suggest that enrichment of ICAM-1 near approximately 43% of these junctions makes these locations preferred for transmigration by signaling the location of a nearby portal, as well as preparing the endothelial cell (EC) junctions, to accommodate leukocyte passage. Blockade of the extracellular domain of the ICAM-1 significantly reduced transmigration (by 68.8 + or - 4.5%) by reducing the ability of leukocytes to get to these portals. In contrast, blockade of the cytoplasmic tail of ICAM-1 reduced transmigration (by 71.1 + or - 7.0%) by disabling VE-cadherin rearrangement. Importantly, venular convergences are optimally equipped to support leukocyte transmigration. Differences in EC morphology result in a significantly higher number of tricellular junctions in convergences compared with straight venular regions (20.7 + or - 1.2 versus 12.43 + or - 1.1/6000 microm(2), respectively). Consequently, leukocyte adhesion and transmigration are significantly higher in convergences compared with straight regions (1.6- and 2.6-fold, respectively). Taken together, these data identify an important role for EC morphology and expression patterns of ICAM-1 in leukocyte transmigration. PMID- 20363970 TI - Plasma cells and nonplasma B cells express differing IgE repertoires in allergic sensitization. AB - The selection of allergen-specific B cells into the plasma cell (PC) pool is a critical step in the immune dysregulation that leads to the production of IgE in allergic diseases. We sought to characterize the murine IgE repertoire. In particular, we questioned whether the IgE repertoire of plasmablasts (PBs)/PCs differs from the IgE repertoire of non-PCs. Therefore, we sorted splenocytes from OVA-sensitized BALB/c mice into CD138(pos) (PBs/PCs) and CD19(pos)/CD138(neg) (non-PCs) B cell fractions. Using reverse transcription PCR, we amplified, cloned, and sequenced IgE mRNA transcripts and analyzed the Ig H chain repertoire. As a reference, we characterized the IgM repertoire of the same animals. Compared to IgM, the IgE sequences contained a significantly higher level of somatic mutations and displayed an oligoclonal expansion with clonotype restriction. Interestingly, we found two phenotypically distinct IgE-producing B cell subpopulations that differed in their repertoire of H chain transcripts; IgE transcripts from PBs/PCs showed significantly more signs of Ag-driven selection than transcripts from non-PCs, including 1) a higher number of somatic mutations, 2) increased clustering of replacement mutations in the CDRs, and 3) biased third CDR of the heavy Ig chain composition. In conclusion, PBs/PCs and non-PCs from OVA-sensitized mice express distinct IgE repertoires, suggesting that 1) the repertoire of IgE-expressing PBs/PCs represents a highly biased selection from the global B cell repertoire and 2) Ag-driven affinity maturation is a major force that selects IgE-producing B cells into the CD138(pos) PC pool. PMID- 20363971 TI - Differential but direct abolishment of human regulatory T cell suppressive capacity by various TLR2 ligands. AB - CD4(+)CD25(high) regulatory T cells (Tregs) control cellular immune responses and maintain peripheral tolerance. We investigated whether TLR2 ligands are able to abrogate Treg-induced suppression in humans based on different reports about effects of triacylated lipopeptide Pam(3)CSK4 in mice. Pretreatment of human Tregs with a mixture of TLR2 ligands Pam(2)CSK4, FSL-1, and Pam(3)CSK4 reduced the Treg-mediated suppression of CD4(+)CD25(-) responder T cells in the majority of the analyzed donors. Differential effects of individual TLR2 ligands are explained by usage of different TLR2 heterodimers in the recognition of Pam(2)CSK4, FSL-1, and Pam(3)CSK4. In contrast to the murine system, TLR2 ligand mediated abrogation of human Treg function was not associated with a downregulation of FoxP3 transcription factor. Furthermore, our results excluded an effect of TLR2 ligands on granzyme A/B release by human Tregs as a potential mechanism to abolish Treg-mediated suppression. Our data suggest that a downregulation of p27(Kip1) and restoration of Akt phosphorylation in human Tregs pretreated with TLR2 ligands result in a reversal of suppression on responder T cells. Moreover, our data indicate that a mixture of TLR2 ligands can be used to modulate human Treg activity. PMID- 20363972 TI - Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation. AB - We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice (FAST(-/-)) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. FAST(-/-) mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST(-/-) mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-alpha and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because FAST(-/-) neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation. PMID- 20363974 TI - A steady state of CD4+ T cell memory maturation and activation is established during primary subtype C HIV-1 infection. AB - The functional integrity of CD4(+) T cells is crucial for well-orchestrated immunity and control of HIV-1 infection, but their selective depletion during infection creates a paradox for understanding a protective response. We used multiparameter flow cytometry to measure activation, memory maturation, and multiple functions of total and Ag-specific CD4(+) T cells in 14 HIV-1- and CMV- coinfected individuals at 3 and 12 mo post HIV-1 infection. Primary HIV-1 infection was characterized by elevated levels of CD38, HLA-DR, and Ki67 in total memory and Gag-specific CD4(+) and CD8(+) T cells. In both HIV-infected and 15 uninfected controls, the frequency of activated cells was uniformly distributed among early differentiated (ED; CD45RO(+)CD27(+)), late differentiated (CD45RO(+)CD27(-)), and fully differentiated effector (CD45RO(-)CD27(-)) memory CD4(+) T cells. In HIV-1-infected individuals, activated CD4(+) T cells significantly correlated with viremia at 3 mo postinfection (r = 0.79, p = 0.0007) and also harbored more gag provirus DNA copies than nonactivated cells (p = 0.04). Moreover, Gag-specific ED CD4(+) T cells inversely associated with plasma viral load (r = -0.87, p < 0.0001). Overall, we show that low copy numbers of gag provirus and plasma RNA copies associated with low CD4 activation as well as accumulation of ED HIV-specific CD4(+) memory. Significant positive correlations between 3 and 12 mo activation and memory events highlighted that a steady state of CD4(+) T cell activation and memory maturation was established during primary infection and that these cells were unlikely to be involved in influencing the course of viremia in the first 12 mo of HIV-1 infection. PMID- 20363973 TI - Interdisciplinary analysis of HIV-specific CD8+ T cell responses against variant epitopes reveals restricted TCR promiscuity. AB - HIV-1-specific CTL responses play a key role in limiting viral replication. CTL responses are sensitive to viral escape mutations, which influence recognition of the virus. Although CTLs have been shown to recognize epitope variants, the extent of this cross-reactivity has not been quantitatively investigated in a genetically diverse cohort of HIV-1-infected patients. Using a novel bioinformatic binding prediction method, we aimed to explain the pattern of epitope-specific CTL responses based on the patients' HLA genotype and autologous virus sequence quantitatively. Sequences covering predicted and tested HLA class I-restricted epitopes (peptides) within the HIV-Gag, Pol, and Nef regions were obtained from 26 study subjects resulting in 1492 patient-specific peptide pairs. Epitopes that were recognized in ELISPOT assays were found to be significantly more similar to the autologous virus than those that did not elicit a response. A single substitution in the presented epitope decreased the chance of a CTL response by 40%. The impact of sequence similarity on cross-recognition was confirmed by testing immune responses against multiple variants of six selected epitopes. Substitutions at central positions in the epitope were particularly likely to result in abrogation of recognition. In summary, the presented data demonstrate a highly restricted promiscuity of HIV-1-specific CTL in the recognition of variant epitopes. In addition, our results illustrate that bioinformatic prediction methods are useful to study the complex pattern of CTL responses exhibited by an HIV-1-infected patient cohort and for identification of optimal targets for novel therapeutic or vaccine approaches. PMID- 20363976 TI - Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. AB - Inhibiting signal transduction induced by inflammatory cytokines offers a new approach for the treatment of autoimmune diseases such as rheumatoid arthritis. Kinase inhibitors have shown promising oral disease-modifying antirheumatic drug potential with efficacy similar to anti-TNF biologics. Direct and indirect inhibition of the JAKs, with small molecule inhibitors like CP-690,550 and INCB018424 or neutralizing Abs, such as the anti-IL6 receptor Ab tocilizumab, have demonstrated rapid and sustained improvement in clinical measures of disease, consistent with their respective preclinical experiments. Therefore, it is of interest to identify optimized JAK inhibitors with unique profiles to maximize therapeutic opportunities. INCB028050 is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. Significant efficacy, as assessed by improvements in clinical, histologic and radiographic signs of disease, was achieved in the rat adjuvant arthritis model with doses of INCB028050 providing partial and/or periodic inhibition of JAK1/JAK2 and no inhibition of JAK3. Diminution of inflammatory Th1 and Th17 associated cytokine mRNA levels was observed in the draining lymph nodes of treated rats. INCB028050 was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects. These data suggest that fractional inhibition of JAK1 and JAK2 is sufficient for significant activity in autoimmune disease models. Clinical evaluation of INCB028050 in RA is ongoing. PMID- 20363975 TI - Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner. AB - Chemerin peptides represent a recently identified component of the endogenous anti-inflammatory network that act via the G protein-coupled receptor ChemR23. The role of the chemerin peptide/ChemR23 pathway in phagocytosis, the clearance of apoptotic cells (efferocytosis), and the resolution of inflammation is unknown. In this article, we report that low picomolar concentrations of the chemerin peptide chemerin15 (C15) enhance macrophage (MPhi) phagocytosis of microbial particles and apoptotic cells by up to 360% in vitro. These prophagocytic effects of C15 are significantly impaired in ChemR23(-/-) MPhis and are associated with increased actin polymerization and localization of F-actin to the phagocytic cup. Importantly, pharmacological inhibition of Syk activity completely abrogates the prophagocytic activities of C15 and associated changes in actin polymerization and phagocytic cup formation, suggesting that C15 promotes phagocytosis by facilitating phagocytic cup development in a Syk dependent manner. During peritoneal inflammation, C15 administration (8 pg/mouse) enhances microbial particle clearance and apoptotic neutrophil ingestion by MPhis in wild-type but not ChemR23(-/-) mice, such that levels of apoptotic and necrotic cells at the inflammatory site are profoundly reduced. In contrast, neutralization of endogenous chemerin species during peritoneal inflammation significantly impairs MPhi ingestion of apoptotic neutrophils and zymosan. Our data identify a key role of the chemerin peptide/ChemR23 axis in the efficient clearance of foreign material, efferocytosis, and, hence, the resolution of inflammation. Manipulation of the chemerin peptide/ChemR23 axis may represent a novel therapeutic approach for the treatment of inflammatory pathologies, especially if failure to efficiently clear phagocytic targets has been implicated in their pathogenesis. PMID- 20363977 TI - Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: potential targets of a streptococcal-induced autoimmune response in psoriasis. AB - Psoriasis is an HLA-Cw6-associated T cell-mediated autoimmune disease of the skin that is often triggered by streptococcal angina. To identify keratinocyte proteins, which may become psoriatic autoantigens as the result of an immune response against streptococci, rabbits were immunized with heat-killed Streptococcus pyogenes. Streptococcal immunization induced Ab formation against various human keratinocyte proteins. Sera from psoriasis patients reacted against several of these proteins as well. Common serologic reactivities of rabbits and patients included the proteins ezrin, maspin, peroxiredoxin 2 (PRDX2), heat shock protein (hsp)27, and keratin 6. When used for stimulation of blood lymphocytes, ezrin, maspin, PRDX2, and hsp27 induced increased T cell activation in psoriasis patients, which was particularly evident for HLA-Cw6(+) individuals. Ag-specific T cell lines generated with these proteins consisted predominantly of CD8(+) T cells and used TCR beta-chain rearrangements, which were highly homologous to those expanded within the corresponding skin lesion. Several immunodominant epitopes on the different proteins could be defined according to sequence alignments with the whole genome of S. pyogenes. Our data indicate that maspin, ezrin, PRDX2, hsp27, and potentially keratin 6 could act as autoantigens of a streptococcal-induced autoimmune response and represent targets of the exaggerated T cell response in psoriasis. Additionally, ezrin and hsp27 might constitute antigenic links between psoriasis and inflammatory bowel disease, uveitis, or arteriosclerosis, which are clinically associated. PMID- 20363978 TI - Nonobese diabetic congenic strain analysis of autoimmune diabetes reveals genetic complexity of the Idd18 locus and identifies Vav3 as a candidate gene. AB - We have used the public sequencing and annotation of the mouse genome to delimit the previously resolved type 1 diabetes (T1D) insulin-dependent diabetes (Idd)18 interval to a region on chromosome 3 that includes the immunologically relevant candidate gene, Vav3. To test the candidacy of Vav3, we developed a novel congenic strain that enabled the resolution of Idd18 to a 604-kb interval, designated Idd18.1, which contains only two annotated genes: the complete sequence of Vav3 and the last exon of the gene encoding NETRIN G1, Ntng1. Targeted sequencing of Idd18.1 in the NOD mouse strain revealed that allelic variation between NOD and C57BL/6J (B6) occurs in noncoding regions with 138 single nucleotide polymorphisms concentrated in the introns between exons 20 and 27 and immediately after the 3' untranslated region. We observed differential expression of VAV3 RNA transcripts in thymocytes when comparing congenic mouse strains with B6 or NOD alleles at Idd18.1. The T1D protection associated with B6 alleles of Idd18.1/Vav3 requires the presence of B6 protective alleles at Idd3, which are correlated with increased IL-2 production and regulatory T cell function. In the absence of B6 protective alleles at Idd3, we detected a second T1D protective B6 locus, Idd18.3, which is closely linked to, but distinct from, Idd18.1. Therefore, genetic mapping, sequencing, and gene expression evidence indicate that alteration of VAV3 expression is an etiological factor in the development of autoimmune beta-cell destruction in NOD mice. This study also demonstrates that a congenic strain mapping approach can isolate closely linked susceptibility genes. PMID- 20363981 TI - Assessing risk for sexual recidivism: some proposals on the nature of psychologically meaningful risk factors. AB - Risk assessment and treatment for sexual offenders should focus on individual characteristics associated with recidivism risk. Although it is possible to conduct risk assessments based purely on empirical correlates, the most useful evaluations also explain the source of the risk. In this review, the authors propose that the basic requirements for a psychologically meaningful risk factor are (a) a plausible rationale that the factor is a cause of sexual offending and (b) strong evidence that it predicts sexual recidivism. Based on the second of these criteria, the authors categorize potential risk factors according to the strength of the evidence for their relationship with offending. The most strongly supported variables should be emphasized in both assessment and treatment of sexual offenders. Further research is required, however, to establish causal connections between these variables and recidivism and to examine the extent to which changes in these factors leads to reductions in recidivism potential. PMID- 20363980 TI - Global survey of escape from X inactivation by RNA-sequencing in mouse. AB - X inactivation equalizes the dosage of gene expression between the sexes, but some genes escape silencing and are thus expressed from both alleles in females. To survey X inactivation and escape in mouse, we performed RNA sequencing in Mus musculus x Mus spretus cells with complete skewing of X inactivation, relying on expression of single nucleotide polymorphisms to discriminate allelic origin. Thirteen of 393 (3.3%) mouse genes had significant expression from the inactive X, including eight novel escape genes. We estimate that mice have significantly fewer escape genes compared with humans. Furthermore, escape genes did not cluster in mouse, unlike the large escape domains in human, suggesting that expression is controlled at the level of individual genes. Our findings are consistent with the striking differences in phenotypes between female mice and women with a single X chromosome--a near normal phenotype in mice versus Turner syndrome and multiple abnormalities in humans. We found that escape genes are marked by the absence of trimethylation at lysine 27 of histone H3, a chromatin modification associated with genes subject to X inactivation. Furthermore, this epigenetic mark is developmentally regulated for some mouse genes. PMID- 20363979 TI - Homotypic clusters of transcription factor binding sites are a key component of human promoters and enhancers. AB - Clustering of multiple transcription factor binding sites (TFBSs) for the same transcription factor (TF) is a common feature of cis-regulatory modules in invertebrate animals, but the occurrence of such homotypic clusters of TFBSs (HCTs) in the human genome has remained largely unknown. To explore whether HCTs are also common in human and other vertebrates, we used known binding motifs for vertebrate TFs and a hidden Markov model-based approach to detect HCTs in the human, mouse, chicken, and fugu genomes, and examined their association with cis regulatory modules. We found that evolutionarily conserved HCTs occupy nearly 2% of the human genome, with experimental evidence for individual TFs supporting their binding to predicted HCTs. More than half of the promoters of human genes contain HCTs, with a distribution around the transcription start site in agreement with the experimental data from the ENCODE project. In addition, almost half of the 487 experimentally validated developmental enhancers contain them as well--a number more than 25-fold larger than expected by chance. We also found evidence of negative selection acting on TFBSs within HCTs, as the conservation of TFBSs is stronger than the conservation of sequences separating them. The important role of HCTs as components of developmental enhancers is additionally supported by a strong correlation between HCTs and the binding of the enhancer associated coactivator protein Ep300 (also known as p300). Experimental validation of HCT-containing elements in both zebrafish and mouse suggest that HCTs could be used to predict both the presence of enhancers and their tissue specificity, and are thus a feature that can be effectively used in deciphering the gene regulatory code. In conclusion, our results indicate that HCTs are a pervasive feature of human cis-regulatory modules and suggest that they play an important role in gene regulation in the human and other vertebrate genomes. PMID- 20363982 TI - Twice-weekly intravenous treatment of pancreatic cancer with atrial natriuretic peptide and vessel dilator. AB - BACKGROUND: Atrial natriuretic peptide (ANP) and vessel dilator eliminate 80% and 33% of human pancreatic adenocarcinomas growing in athymic mice when given subcutaneously for 28 days via osmotic pumps. MATERIALS AND METHODS: To determine if similar beneficial effects can be obtained by ANP and vessel dilator on a bi weekly basis, bolus infusion via vascular ports bi-weekly for 4 weeks was given to athymic mice bearing human pancreatic adenocarcinomas. RESULTS: Vessel dilator and ANP (each at 100 microM) (n=6 for each) resulted in a 33% (p<0.01) and 17% (p<0.05) elimination of human pancreatic adenocarcinomas, respectively, while the tumor volume increased 64-fold (p<0.001) in the placebo-treated mice (n=12). During the 4 weeks of treatment, the growth velocity decreased 92% and 68% with vessel dilator and ANP, respectively, compared to untreated mice. CONCLUSION: Biweekly vessel dilator and ANP both eliminate some human pancreatic adenocarcinomas in athymic mice. PMID- 20363983 TI - Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats. AB - This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella, in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats. PMID- 20363984 TI - Renal uptakes of 99mTc-MAG3, 99mTc-DTPA, and 99mTc-DMSA in rabbits with unilateral ureteral obstruction. AB - Renal function measurements using (99m)Tc-DTPA and (99m)Tc-MAG(3) dynamic scintigraphs were compared to those obtained using (99m)Tc-DMSA static scintigraphy. Eighteen experimental rabbits were randomly divided into (99m)Tc DTPA-, (99m)Tc-MAG(3)-, and (99m) Tc-DMSA-injected groups. Experimental unilateral renal damage was induced by ligating a unilateral right ureter in 18 rabbits. Scintigraphic images were obtained at 2 and 5 h after intravenous injection of (99m)Tc-DMSA, or immediately after administration of (99m)Tc-DTPA or (99m)Tc-MAG(3). For the dynamic images using (99m)Tc-DTPA and (99m)Tc-MAG(3), rapid sequential images were obtained every 2 s for 30 images up to 1 min. The three groups presented different relative renal functions between the left normal and the right abnormal kidneys at 1, 2, 3, and 4 weeks post-ligation (p<0.05). However, the between-group comparisons showed no significant differences at any time. These results suggest that dynamic images of (99m)Tc-DTPA and (99m)Tc MAG(3) can be used to measure the relative renal function in place of the static image of (99m)Tc-DMSA. PMID- 20363985 TI - Modulation of aged murine T lymphocytes in vivo by DPV576-C, a nanodiamond- and nanoplatinum-coated material. AB - BACKGROUND: Nanotechnology is rapidly emerging in biomedical applications, including cancer therapy. Here, a mixture of ultra dispersed nanodiamond and nanoplatinum was coated onto fabrics in the form of a cloth (DPV576-C). The role of DPV576-C in modulating T lymphocytes of aged mice was examined. MATERIALS AND METHODS: C57BL/6 mice were treated with DPV576-C as a lining in a mouse house for 1 month. Splenic cells were analyzed for CD4(+) and CD8(+) T-cells and NK activity using flow cytometry. RESULTS: DPV576-C-treated aged mice showed an: (1) increase in the percentages of CD4(+) and CD8(+) T-cells and their activation markers, CD25 and CD69, over untreated aged mice; (2) enhancement of NK activity; and (3) absence of adverse side effects as determined histopathologically. CONCLUSION: The enhancement of lymphocytes by DPV576-C may be useful for patients suffering from immune dysfunction. PMID- 20363986 TI - Chronic hind limb ischemia reduces myocardial ischemia-reperfusion injury in the rabbit heart by promoting coronary angiogenesis/arteriogenesis. AB - BACKGROUND/AIM: Application of ischemic injury in a remote organ may provide protection of other tissues against ischemia. We hypothesized that ischemia in the rabbit hind limb protects against myocardial ischemia by increasing angiogenesis/arteriogenesis. MATERIALS AND METHODS: In the first experiment, severe limb ischemia (LI) was induced in 26 New Zealand White rabbits by excision of the femoral artery while another 26 served as controls (no ischemia; sham operation [SHO]). Four weeks later, the blood vessels of the subendocardial and intramyocardial areas of the excised hearts were counted. In the second experiment, 14 LI rabbits and 14 SHO controls were subjected to 30 min of regional heart ischemia and 3 h reperfusion. Infarct size and the areas-at-risk were determined. RESULTS: Compared with controls, LI rabbits showed more subendocardial (103+/-14 vs. 113+/-13 capillaries/mm2, respectively; p=0.01) and intramyocardial blood vessels (102+/-12 vs. 114+/-16 capillaries/mm(2), respectively; p=0.009). LI rabbits had significantly smaller infarct size compared with the SHO animals (infarct areas/areas-at-risk: 14.37+/-11.23% vs. 31.31+/-13.73%, respectively; p=0.003). CONCLUSION: Chronic hind LI reduces myocardial infarct size by promoting coronary angiogenesis/arteriogenesis in an experimental model. PMID- 20363987 TI - Carbon nanotubes induce granulomas but not mesotheliomas. AB - BACKGROUND: Different types of carbon nanotubes may represent toxic hazards due to their size distribution and massive surface area. They may adsorb other toxic agents that can consequently be transported into the body. Hence the aim of this study was to confirm or reject the hypothesis of carcinogenicity of two types of carbon nanotubes. MATERIALS AND METHODS: Well-defined single-walled and multi walled carbon nanotubes were studied in a specific animal model for mesothelioma induction. RESULTS: Short-term pilot studies were published on the asbestos fibre like mesothelioma-inducing effects of carbon nanotubes based on the proposed mechanistic correlation on health effects of fibres of the same size. Our results with a simple in vivo, peritoneal exposure model refute such an interpretation. The present studies with rats indicate that early granuloma formation does not lead to the development of mesotheliomas during chronic exposure of peritoneal mesothelium to either single- or multi-walled carbon nanotubes of varied size. CONCLUSION: Due to the limited toxicity data on carbon nanotubes, these results may be particularly important for risk assessment purposes. PMID- 20363988 TI - Oxytocin both increases proliferative response of peripheral blood lymphomonocytes to phytohemagglutinin and reverses immunosuppressive estrogen activity. AB - BACKGROUND: It has been shown that the neurohypophyseal peptide oxytocin is present in the human thymus and in vitro it can mimic interleukin (IL)-2 action in the induction of interferon-gamma production. In the present study, we tested the capacity of oxytocin to modulate the response of peripheral blood mononuclear cells (PBMCs) to phytohemagglutinin (PHA) and its ability to change the membrane expression of IL-2 receptor CD25 and the CD95 activation marker. Furthermore, whether oxytocin was able to reverse the inhibition of PBMC blastic response and CD25 expression induced by estradiol benzoate (E(2)B) was studied. PATIENTS AND METHODS: Fifteen healthy women were studied with a mean age of 33.8 years, no previous pregnancies, all in the early follicular phase of the cycle with normal values of circulating estrogens. RESULTS: The addition of oxytocin (1x10(-10) M, 1x10(-11) M, 1x10(-12) M) significantly increased the PBMC blastic response to PHA as well as the expression of both CD25 and CD95. These results were due to interaction of oxytocin with its specific receptor since the addition of an oxytocin antagonist completely reversed the oxytocin activity. In contrast, E(2)B induced a marked decrease of PHA-stimulated PBMC cell cycle progression and CD25 expression: the inhibitory effect of E(2)B was significantly counteracted by low concentrations of oxytocin. CONCLUSION: The present results support the hypothesis that neuropeptides may act as a link in the network between the immune and the neuroendocrine systems. PMID- 20363989 TI - Experimental xenoimplantation of antlerogenic cells into mandibular bone lesions in rabbits: two-year follow-up. AB - Different types of cells require activation, and take part in annual, dynamic growth of deer antlers. Stem cells play the most important role in this process. This report shows the results of a two-year long observation of xenogenic implant of antlerogenic stem cells (cell line MIC-1). The cells were derived from growing antler of a deer (Cervus elaphus), seeded onto Spongostan and placed in postoperative lesions of mandibular bones of 15 experimental rabbits. The healing process observed in the implantation sites in all rabbits was normal, and no local inflammatory response was ever observed. Histological and immunohistochemical evaluations were performed after 1, 2, 6, 12 and 24 months, and confirmed the participation of xenogenic cells in the regeneration processes, as well as a lack of rejection of the implants. The deficiencies in the bones were replaced by newly formed, thick fibrous bone tissue that underwent mineralization and was later remodelled into lamellar bone. The results of the experiment with rabbits allow us to believe that antlerogenic cells could be used in reconstruction of bone tissues in other species as well. PMID- 20363990 TI - 17beta-estradiol acting as an electron mediator: experiments in vitro. AB - BACKGROUND: The present work reports on the effect of oxidizing (OH, O(2)(*-)) and reducing free radicals (e(-)(aq), H) on 17beta-estradiol (17betaE2) in respect to breast cancer initiation. The objectives of the study were based on the following premise: the ability of 17betaE2 to emit electrons (e(-)(aq)) as well as to transfer them to other biological systems. Thereby, the resulting transient hormone products are leading to the formation of metabolites, some of which may initiate the neoplastic process. The present work considers the effect of the simultaneously generated oxidizing and reducing free radicals on the carcinogenic properties of the 17betaE2 metabolites. MATERIALS AND METHODS: Water soluble 17betaE2 with incorporated 2-hydroxypropyl-beta-cyclodextrin (HBC) in various aqueous media (pH ~7.4), saturated with air, N(2)O or argon, as well as HBC alone, were exposed to the action of free radicals produced by gamma-ray. Escherichia coli bacteria (AB 1157) were used as a model for living systems. RESULTS: From the survival curves obtained under different conditions, the derived DeltaD(37) values (representing the radiation dose at which N/N(0)=0.37; N/N(0) ratio: N(0)=starting number of colonies, N=number after irradiation treatment) illustrate that 17betaE2 as well as HBC act as very powerful scavengers of OH and O(2)(*-) radicals. On the other hand, 17betaE2 and HBC intermediates resulting from attack of the reducing species (e(-)(aq), H) have strong anticancer properties. CONCLUSION: It is stated that DeltaD(37) values strongly depend on the reactivity of the individual free radicals. Oxidizing free radicals lead to positive DeltaD(37) values, illustrating the strongly pronounced radiation protecting ability of the systems. On the contrary, the primary reducing free radicals result in negative DeltaD(37) values, indicating anticancer effect. PMID- 20363991 TI - Association between CDKN1A Ser31Arg and C20T gene polymorphisms and colorectal cancer risk and prognosis. AB - BACKGROUND: CDKN1A (p21(WAF1/CIP1)) plays an important role in cell cycle regulation. Somatic alterations in genes which regulate cell division have been shown to be related to different types of cancer prognosis and survival. The purpose of this study was to investigate the effect of the CDKN1A Ser31Arg and C20T gene polymorphisms in Turkish patients with colorectal cancer. PATIENTS AND METHODS: CDKN1A Ser/Arg and C20T polymorphisms were studied in 53 patients with colorectal cancer and 64 healthy controls. Genomic DNA was amplified by polymerase chain reaction (PCR) and genotypes were determinated by the restriction fragment length polymorphism (RFLP) method. RESULTS: There were statistically significant differences in the distribution of CDKN1A Ser/Arg genotypes and allele frequencies between colorectal cancer patients and healthy controls (p=0.040 and p=0.01, respectively). CDKN1A C20T genotype frequency did not show any significant differences between patients and controls. We combined the results for C20T and Ser31Arg polymorphisms and observed that a lower risk of colorectal cancer was associated with CT/SerArg combined genotypes compared to controls and this difference was statistically significant (p=0.024; odds ratio (OR)=0.322, 95% confidence interval (CI)=0.114-0.912). C20T C allele and SerSer genotypes significantly increased risk compared to other combined genotypes (p=0.034; OR=1.265, 95% CI=1.020-1.569). CONCLUSION: The results of present study demonstrated that, potentially, CDKN1A functional polymorphisms may contribute to the risk of colorectal cancer in Turkish. PMID- 20363992 TI - Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary referral centre in Norway. AB - BACKGROUND: We aimed to compare patients reporting acute infection with those reporting no infection at onset of chronic fatigue syndrome (CFS). PATIENTS AND METHODS: This study includes 873 patients with CFS referred to a tertiary centre on average 4.8 years after symptom onset. Assessment was by both observer query and self-reports. Antibody analyses against infectious agents including Epstein Barr virus and enterovirus were performed in a majority of patients. RESULTS: Females comprised 75.3% of the patient group, and the mean age was 33 years. Initial infection was reported by 77%. There was no difference as to antibody analyses. Logistic regression showed that initial infection was independently associated with acute onset of fatigue, improvement of fatigue at referral, and the following symptoms at referral: fever, tender lymph nodes, and myalgia. CONCLUSION: CFS patients with initial infection as a precipitating factor more often report acute onset of fatigue, more frequent accompanying symptoms, and more frequent improvement on referral than do patients without initial infection. PMID- 20363993 TI - Effect of atorvastatin on cellular adhesion molecules on leukocytes in patients with normocholesterolemic coronary artery disease. AB - BACKGROUND: Expression of cellular adhesion molecules on leukocytes plays a key role in coronary artery disease (CAD). The aim of the present study was to assess whether atorvastatin therapy has an impact on the expression of cellular adhesion molecules on leukocytes in patients with normocholesterolemic CAD. PATIENTS AND METHODS: In 54 patients with CAD and atorvastatin treatment and 54 CAD patients without atorvastatin therapy, expression of CD40L, CD11a, CD11b, CD54, CD62L and CD41 on leukocytes was measured using flow cytometry. All patients were normocholesterolemic. RESULTS: Atorvastatin treatment led to a significantly lower expression of CD40L, CD11b and CD54 on monocytes (p<0.05) and neutrophils (p<0.05). Expression of CD11a was significantly lower on monocytes (p<0.05) in atorvastatin-treated patients. CONCLUSION: The present results indicate that atorvastatin apparently improves chronic inflammation and may have a beneficial effect on hemostasis by reducing the expression of cellular adhesion molecules on leukocytes. PMID- 20363994 TI - Spirometric reference values in greek children and adolescents. AB - AIM: This study was performed to describe the relationship among anthropometric parameters and lung function in Greek children, to produce reference values for spirometry and to compare these results with other data sets. PATIENTS AND METHODS: Spirometric values were measured with electronic portable Spirometer Spirolab II (MIR) in 414 healthy, nonsmoking Greek children, aged 6-18 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height, weight and body mass index (BMI). RESULTS: The highest correlation was found with height. Predictive equations for: forced expiratory volume in the first sec (FEV(1)), forced vital capacity (FVC), forced expiratory flow from 25%-75% of the vital capacity (FEF(25-75%)) and peak expiratory flow (PEF) with standing height as the dependent variable are presented for both sexes. Our reference values are close to those of other European children. CONCLUSION: The developed predictive equations can be used in clinical practice in Greece and in other neighboring Balkan countries. PMID- 20363995 TI - Development of fMRI tests for children with central auditory processing disorders. AB - The term 'central auditory processing disorder' (CAPD; in German-speaking countries: 'auditive Verarbeitungs- und Wahrnehmungsstorung', AVWS) embraces various complex disorders of central auditory function. The purpose of this preliminary study was to develop a functional magnetic resonance imaging (fMRI) test set in order to extend the diagnostic work-up to include imaging, and thus to improve both diagnostic performance and the monitoring of treatment outcome. fMRI was performed in 11 healthy children ranging in age from 7 to 10 years and in 11 healthy adults (age range: 23 to 31 years). Three tests, used for diagnosis of CAPD, served as the basis for fMRI paradigms: the Hannover phoneme discrimination test (HPDT); the auditory memory span test (MST) and the dichotic listening test (DLT). In the HPDT, activations in the dorsal part of the superior temporal gyrus (STG) were found on both sides, in the Broca area and in the left middle temporal gyrus, typical for phonemic tasks. The MST showed bilateral activations of the STG, typical for processing of pseudo-words. In addition, bilateral activation of the hippocampus was found. However, there was no clear activity in the left supramarginal gyrus, where the phonological store is thought to be located. The DLT showed activations of the bilateral STG and of the left inferior frontal gyrus. Predominantly, the paradigms showed typical activation patterns of the examined central auditory functions. These results can serve as a reference for future examinations in children with AVWS/CAPD. PMID- 20363996 TI - Multiple distant metastases of hepatocellular carcinoma to the oral cavity. AB - We describe the palliative therapy for multiple metachronous oral metastases of hepatocellular carcinoma in a 72-year-old patient with emphasis on maintaining oral functions by local debulking procedures in due consideration of the dissemination of the neoplasm to multiple organs. The first oral metastasis was the first evidence of multiple tumor spread after partial hepatectomy. Palliative chemotherapy with sorafenib was cancelled after three weeks due to tumor progression and hemiplegia following brain metastasis and stroke. Periodical screening of the patient for oral findings allowed the non-mutilating excision of further oral metastases at an early stage with no signs of local recurrence during the follow-up period. Oral metastases from hepatocellular carcinoma appear to occur more frequently than formerly supposed. PMID- 20363997 TI - Iterative surgical resection of a recurrent gallbladder carcinoma with long-term survival: report of a case. AB - Gallbladder carcinoma is a rare, but often lethal disease. Unfortunately, at the time of diagnosis, patients usually have advanced disease (T3-T4) and long-term survival is dismal, ranging from 5 to 12% in the literature. However, this cancer can be successfully treated when the tumour is organ-confined (T1-T2 tumours), as happens in the case of incidental diagnosis at the time of cholecystectomy for gallstones. Here we describe a patient with recurrent gallbladder carcinoma who, treated with iterative surgical resection, is alive and disease-free at 5 years after the final surgical procedure. PMID- 20363998 TI - The use of the Veress needle to drain mammary periprosthetic fluid. AB - BACKGROUND: The most common early complications associated with mammary implants are seroma and haematoma formation, and acute infection. The aspiration of fluid around the prosthesis can help to diagnose and correctly treat these complications. The use of a needle with a sharp tip can damage the implant. We present our experience in removing periprosthetic fluid using the atraumatic Veress needle. PATIENTS AND METHODS: Twelve patients with breast implants presented with a progressive monolateral breast enlargement. Ultrasound examination revealed the collection of fluid around the implants. Ultrasound guided percutaneous needle aspiration of the fluid was performed using the Veress needle. RESULTS: No complications were reported. None of the implants was found to be damaged at the ultrasound assessment. CONCLUSION: Our proposed use of the Veress needle is similar to the use for which it was designed. Indeed, we used the device to remove some fluid from a real cavity. This procedure proved to be effective and safe. PMID- 20363999 TI - The role of carbon dioxide therapy in the treatment of chronic wounds. AB - A wound is defined as chronic when it does not heal according to the normal repair times and mechanisms. This particular condition may be principally due to local hypoxia. Carbon dioxide (CO(2)) therapy refers to the transcutaneous or subcutaneous administration of CO(2) for therapeutical effects on both microcirculation and tissue oxygenation. In this study, we report the clinical and instrumental results of the application of CO(2) in the therapy of chronic wounds. The study included 70 patients affected by chronic ulcers. The patients were selected by aetiology and wound extension and equally divided into two homogeneous groups. In group A, CO(2) therapy was used in addition to the routine methods of treatment for such lesions (surgical and/or chemical debridement, advanced dressings according to the features of each lesion). In group B, patients were treated using routine methods alone. Both groups underwent to instrumental (laser doppler flow, measurement of TcPO(2)), clinical and photographic evaluation. In the group that underwent subcutaneous treatment with CO(2) therapy, the results highlighted a significant increase in tissue oxygenation values, which was confirmed by greater progress of the lesions in terms of both healing and reduction of the injured area. Considering the safety, efficacy and reliability of this method, even if further studies are necessary, we believe that it is useful to include subcutaneous carbon dioxide therapy in the treatment of wounds involving hypoxia-related damage. PMID- 20364000 TI - Impact of adjuvant chemo- and radiotherapy on the cellular immune system of breast cancer patients. AB - The relevance of an uncompromised immune system for the development and progress of breast cancer still is a matter of intensive research. The impact of chemo- and/or radiotherapy on peripheral blood immune cell counts and activity of breast cancer patients (n=660) was investigated by flow cytometry. Not only the absolute counts, but also the comparison of those counts with standard values were evaluated. Most studies do not consider this comparison. As compared to pre treatment values, leukocytes, lymphocytes, B-lymphocytes, T-lymphocytes, helper T cells and CD25(+) T-cells (activated T-cells) were significantly reduced after chemo- and/or radiotherapy. However, mean cell counts remained within the normal range. Statistically non-significant down-regulation was detected for cytotoxic T cells, suppressor T-cells and natural killer cells, which are of prime importance as far as tumor development and defence are concerned. The impact of the therapy is not predictable for individual cases. However, only less than 20% of the breast cancer patients were immunocompromized after chemo- and/or radiotherapy. PMID- 20364001 TI - Complete recovery from undertreated Wernicke-Korsakoff syndrome following aggressive thiamine treatment. AB - BACKGROUND: Wernicke-Korsakoff syndrome (WKS) is a neuropsychiatric condition which results from thiamine deficiency, most commonly due to alcohol abuse. The prognosis of WKS is poor and its outcome depends mainly on prompt treatment. CASE REPORT: A 52-year-old male with a ten-year history of heavy alcohol abuse was admitted in hospital and treated for WKS. Ataxic and oculomotor symptoms promptly reversed following standard treatment but no change was observed in higher mental functioning. Although the protracted WK symptoms made the patient's improvement unlikely, aggressive treatment with thiamine (600 mg/day orally and 300 mg/day intramuscularly) fully reversed the condition within two months. CONCLUSION: Even though prolongation of undertreatment of WKS typically precludes significant improvement of symptoms due to irreversible damage of the brain, at least in some cases, higher thiamine doses (over 500 mg/day) for a longer period (at least three months) than usually recommended should be tried. PMID- 20364002 TI - Dual-headed coincidence PET vs. dedicated PET/CT in the evaluation of thoracic malignancies. AB - The aim of this study was to evaluate the usefulness of coincidence PET imaging as compared with dedicated PET/CT in cancer staging. PATIENTS AND METHODS: Sixteen patients with thoracic malignancies referred to a PET/CT examination accepted to repeat the acquisition with a coincidence PET system. One experienced nuclear medicine physician compiled a report from the PET/CT examinations and the coincidence PET images. The reports were compared and evaluated according to the degree of agreement: no agreement, unsatisfactory, acceptable or satisfying agreement. RESULTS: Satisfying or acceptable agreement between the PET/CT and the coincidence PET examination was found in 14 out of 16 patients (88%). The main issue for the examining physician was to anatomically locate the FDG uptake in the mediastinum in the coincidence PET images. CONCLUSION: The data from this small study imply that the staging results obtained with coincidence PET are in most cases concordant with those obtained with dedicated PET/CT. PMID- 20364003 TI - Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression. AB - BACKGROUND: Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. PATIENTS AND METHODS: The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. RESULTS: a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. CONCLUSION: These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer. PMID- 20364004 TI - Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. AB - Chemokines and their receptors play diverse roles in malignant tumor progression, particularly as key mediators of tumor stroma interactions. C-C motif chemokine ligand 2 (CCL2) also called monocyte chemoattractant protein-1 (MCP-1), belongs to the C-C motif chemokine sub-family and is currently believed to mediate its actions through one receptor, C-C motif chemokine receptor 2 (CCR2). CCL2 has been identified as a major chemokine inducing the recruitment of macrophages in human tumors, including those of the bladder, cervix, ovary, lung and breast. In this study of Turkish women, the association of CCL2 A2518G and CCR2 V64I polymorphisms with endometrial cancer was investigated using 50 endometrial cancer patients and 211 controls. In our study, individuals with CCL2 A2518G GG genotype showed a 6.7-fold increased risk for endometrial cancer (p<0.0001) and individuals with CCL2 A2518G A allele had a 7.14-fold lower risk of endometrium cancer (p<0.0001). Individuals carrying the CCR2 64I/64I genotype had a 4.13-fold increased risk for endometrial cancer (p<0.0001). We also found that individuals carrying the CCR2 wt allele had a 4.16-fold lower risk for endometrial cancer (p=0.005). We observed that the CCL2 G: CCR2 64I haplotype frequency was significantly higher in patients compared to controls (p=0.019). In conclusion, we state that there appears to be an association between polymorphism of CCL2 and its receptor CCR2 and endometrial cancer. To the best of our knowledge, this is the first study to show such an association. PMID- 20364005 TI - Neuropsychological correlates of written expression in college students with ADHD. AB - OBJECTIVE: To examine written expression and the executive function skills (working memory, verbal fluency, and planning and organization) involved in written expression in college-aged students with ADHD. METHOD: Two groups of undergraduate students, aged 19 to 28 years, (ADHD, n = 31; control, n = 27) are evaluated on selected measures of executive function and a measure of written expression. RESULTS: No statistically significant differences are found between groups on measures of executive function and written expression. A standard multiple regression model is significant for predicting writing mechanics, with a measure of behavioral inhibition making a statistically significant contribution. CONCLUSION: Findings from the study provide important information about the link between specific executive function abilities and written expression, particularly for fundamentals in writing in college students. PMID- 20364006 TI - Assessing welfare, honing skills. PMID- 20364007 TI - BVA Council updated on OV negotiations. PMID- 20364008 TI - Salmonellosis in garden birds in Scotland, 1995 to 2008: geographic region, Salmonella enterica phage type and bird species. AB - Salmonellosis was diagnosed in garden birds from 198 incidents in Scotland between September 1995 and August 2008. Salmonellosis was essentially a disease of finches in the north of Scotland, but in the south of Scotland it was also a problem in house sparrows. Almost all of the incidents were caused by Salmonella Typhimurium phage types 40 or 56/variant, but regional variation in phage types was observed. In the north of Scotland, one phage type (DT 40) predominated, but in the south of Scotland two phage types were commonly isolated (DTs 40 and 56/variant, with the latter the more common of the two phage types). This regional difference was statistically significant for salmonellosis in greenfinches, chaffinches and 'other garden birds', but not for house sparrows. Different temporal patterns for different species of bird and different phage types were also observed within regions. These findings suggest that the epidemiology of salmonellosis in garden birds varies depending on the phage type of Salmonella and the species of garden bird, with additional regional differences depending on the wild bird populations and the phage types of Salmonella in circulation. An awareness of these differences will help when formulating guidelines aimed at reducing the impact of salmonellosis in garden birds. PMID- 20364009 TI - Prevalence of viral infections in captive collections of boid snakes in Germany. AB - Data on viral infections in apparently healthy snake collections in Germany were obtained with respect to husbandry conditions and health status. Samples from 100 boid snakes (from 14 collections) were examined microbiologically and for the presence of paramyxoviruses (PMVs) using RT-PCR. Blood was tested for the presence of antibodies against PMV, adenovirus and reovirus and for inclusion bodies indicative of inclusion body disease. Nine snakes tested positive for PMV, and inclusion bodies were detected in six snakes. Antibodies against PMV were found in one snake, and two snakes had antibodies against an adenovirus. A significant correlation was found between the origin of the snake and the presence of PMV, and between the presence of remarkable microbiological findings and husbandry conditions. PMID- 20364010 TI - Clinical aspects of multinodular pulmonary fibrosis in two warmblood horses. AB - Two warmblood horses with a history of chronic weight loss and inappetence were referred to the Faculty of Veterinary Medicine, Ludwig-Maximilians University of Munich, Germany, for further examination. The clinical signs in horse 1 were fever, tachycardia and tachypnoea, and chronic ulcerative keratopathy of both eyes. Horse 2 had severe oral ulcerations and was coughing during feeding. In both horses, increased bronchovesicular sounds were heard during auscultation of the lungs. Laboratory findings included mild anaemia, lymphopenia and hypoalbuminaemia. Radiographic examination of the thorax revealed a severe nodular interstitial pattern. Multiple nodular lesions on the surface of the lung were observed by ultrasonographic examination. Light microscopy of lung biopsy specimens obtained from horse 1 revealed a severe chronic fibrosing interstitial pneumonia. Both horses were eventually euthanased because of a poor prognosis. Postmortem examination confirmed severe multinodular fibrosing interstitial pneumonia in both horses, and lung tissue yielded positive results for equine herpesvirus type 5 DNA using PCR assay. On the basis of the clinical, radiographic and pathological findings, as well as the PCR results, the diagnosis of equine multinodular pulmonary fibrosis was established. PMID- 20364011 TI - Treatment of distal radial/ulnar fractures in 17 toy breed dogs. PMID- 20364012 TI - Presumed nephrogenic diabetes insipidus secondary to chronic copper hepatotoxicity in sheep. PMID- 20364016 TI - Lack of evidence for circovirus involvement in bovine neonatal pancytopenia. PMID- 20364017 TI - Tuberculosis in goats. PMID- 20364018 TI - RCVS retention fees. PMID- 20364019 TI - Uniting research into human and animal health. PMID- 20364020 TI - Stress-induced synthesis of phosphatidylinositol 3-phosphate in mycobacteria. AB - Phosphoinositides play key roles in regulating membrane dynamics and intracellular signaling in eukaryotic cells. However, comparable lipid-based signaling pathways have not been identified in bacteria. Here we show that Mycobacterium smegmatis and other Actinomycetes bacteria can synthesize the phosphoinositide, phosphatidylinositol 3-phosphate (PI3P). This lipid was transiently labeled with [(3)H]inositol. Sensitivity of the purified lipid to alkaline phosphatase, headgroup analysis by high-pressure liquid chromatography, and mass spectrometry demonstrated that it had the structure 1,2 [tuberculostearoyl, octadecenoyl]-sn-glycero 3-phosphoinositol 3-phosphate. Synthesis of PI3P was elevated by salt stress but not by exposure to high concentrations of non-ionic solutes. Synthesis of PI3P in a cell-free system was stimulated by the synthesis of CDP-diacylglycerol, a lipid substrate for phosphatidylinositol (PI) biosynthesis, suggesting that efficient cell-free PI3P synthesis is dependent on de novo PI synthesis. In vitro experiments further indicated that the rapid turnover of this lipid was mediated, at least in part, by a vanadate-sensitive phosphatase. This is the first example of de novo synthesis of PI3P in bacteria, and the transient synthesis in response to environmental stimuli suggests that some bacteria may have evolved similar lipid mediated signaling pathways to those observed in eukaryotic cells. PMID- 20364021 TI - Effects of concomitant temozolomide and radiation therapies on WT1-specific T cells in malignant glioma. AB - OBJECTIVE: Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1 specific T-cells in patients with malignant gliomas. METHODS: Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8(+) T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests. RESULTS: Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, NK cells and NKT cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count. CONCLUSIONS: Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted. PMID- 20364022 TI - Fifteen years of ultrasound guidance in regional anaesthesia: part 1. AB - Ultrasound guidance for regional anaesthesia has gained enormous popularity in the past decade. The use of ultrasound guidance for many regional anaesthetic techniques is common in daily clinical practice, and the number of practitioners using it is increasing. However, alongside the enthusiasm, there should be a degree of informed scepticism. The widespread use of the various techniques of ultrasound-guided regional blocks without adequate training raises the danger of malpractice and subsequent impaired outcome. Adequate education in the use of regional block techniques under ultrasound guidance is essential. This review article addresses ultrasound guidance for regional anaesthesia, and is divided into two parts because of the size of the topic and the number of issues covered. This first part includes a review and preview of ultrasound guidance in regional anaesthesia and discusses all aspects of ultrasound for regional anaesthesia with a focus on recent technical developments, the positive implications in economics, further potential advantages (e.g. detection of anatomical variants, painless performance of blocks) and education. It also attempts to define a 'gold standard' in regional anaesthesia with the most recent findings in adequate volumes of local anaesthetics for peripheral nerve blocks. This standard should include an extraneural needle position, a high success rate, and wide application of ultrasound guidance in regional anaesthesia. The second part describes the impact of ultrasound on the development of nerve block techniques in the past 5 yr. PMID- 20364024 TI - Variants of the BMP15 gene in a cohort of patients with premature ovarian failure. AB - BACKGROUND: Bone morphogenetic protein 15 (BMP15) is an oocyte-derived growth factor acting as a major player in follicle differentiation in mammals. Mutations in the BMP15 gene, some of which lead to defective secretion of bioactive dimers, have been associated with premature ovarian failure (POF) in humans. METHODS: Fifty patients diagnosed with POF with a normal karyotype were included in the study. After DNA extraction and amplification by PCR, the entire coding sequence and intron-exon junctions of BMP15 gene were analysed in the cohort of POF patients and in a control group of 214 patients. RESULTS: Nine variants of the BMP15 gene including six missense substitutions and one insertion of three nucleotides were identified in the POF group. Three of them were previously described as single nucleotide polymorphisms and were also found in the control group. Two variants (H81R and G199R) have not been previously described and were not identified among controls but were not predicted to be deleterious. One variant (A180T) was identified among two POF cases, and also in two controls. One variant (F194S), predicted as potentially deleterious, was identified for the first time in a POF patient but also identified in one control. One variant (L148P), potentially deleterious, previously reported in POF patients, was identified for the first time among controls. The variant 788insTCT, previously identified among POF patients, probably has a low biological impact as it was also found in control patients and is a common polymorphism in sub-Saharan African populations. CONCLUSIONS: Various missense variants of the BMP15 gene were identified among patients with POF. For most variants, the impact of the amino-acid substitution on the protein structure and function was predicted to be low. The two variants predicted as potentially deleterious were also identified among controls and could be considered as rare polymorphisms. Although some of these variants could contribute to the development of POF in a complex manner, the demonstration of their role in the pathogenesis of POF requires additional functional studies. PMID- 20364023 TI - Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004. AB - This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153 237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe. PMID- 20364025 TI - Avoiding transgenerational risks of mitochondrial DNA disorders: a morally acceptable reason for sex selection? AB - In this article, we discuss sex selection not intended to help a couple avoid having a child with a severe genetic disorder, but to avoid possible health risks further along the line of generations. Sex selection may be put to this use in the context of preventing mitochondrial DNA disorders by means of preimplantation genetic diagnosis (PGD) and possibly in the future also through nuclear transfer (NT; also known as mitochondrial gene replacement). A relevant analogy can be found in the context of PGD for X-linked diseases, where sex selection against healthy female carrier embryos would have the same 2-fold purpose of (i) avoiding difficult reproductive decisions for the future child and (ii) avoiding transmission of the mutation to a possible third generation. Because sex selection would still be done for reasons of health, this application should not give rise to the moral concerns associated with sex selection for non-medical reasons. However, the proportionality of adding the relevant procedures to PGD or NT is a relevant concern. We discuss post- and preconceptional sex selection strategies. We conclude that if PGD is already part of the procedure, either as the central technology or as a back-up test after NT, preferentially transferring male embryos could in principle be a morally acceptable way of reducing possible burdens and risks. To start an IVF/PGD-cycle especially for this purpose would be disproportional. The alternative approach of preconceptional sex selection may be morally justified as a means to increase the chances of obtaining male embryos. PMID- 20364026 TI - Synchronous breast cancer and lymphoma: a case series and a review of the literature. AB - Four patients with synchronous breast cancer and lymphoma are described. In all cases, the lymphoma was an unexpected finding in the histopathology of the axillary lymph-node dissection. The diagnosis of synchronous malignancies poses challenges for both the diagnosing pathologist and the treating clinician. PMID- 20364027 TI - Methylation of cyclin-dependent kinase inhibitors, XAF1, JUNB, CDH13 and soluble Wnt inhibitors in essential thrombocythaemia. AB - BACKGROUND: Methylation of genes regulating cell-cycle check-point (INK4 cyclin dependent kinase inhibitors), apoptosis (XAF1), adhesion (CDH13), JUNB and Wnt signalling (soluble Wnt inhibitors) has been implicated in pathogenesis of haematological and epithelial cancers. METHOD: The authors studied the methylation status of CDKN2A, CDKN2B, XAF1, CDH13, JUNB and a panel of soluble Wnt inhibitors including WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5 by methylation-specific PCR in 31 bone marrow and 21 peripheral blood samples of patients with essential thrombocythaemia. RESULTS AND DISCUSSION: There was no evidence of hypermethylation of all these genes in both the BM and PB samples. Therefore, in contrast to myeloid leukaemias, methylation of these genes regulating the cell cycle, apoptosis, adhesion and Wnt signalling does not play an important role in the pathogenesis of myeloproliferative diseases. Whether differential methylation may occur in the progenitor or mature blood cell compartments remains to be verified. Our study contributes to the literature on methylation in chronic myeloproliferatve diseases. PMID- 20364028 TI - Pelvic lymph nodes: distribution and nodal tumour burden of urothelial bladder cancer. AB - AIMS: To evaluate the number of lymph nodes and the lymph node tumour burden in different anatomical pelvic regions to better asses the impact of variations in the extent of lymphadenectomy on reported LN parameters and pelvic tumour clearance. METHODS: 162 patients with lymph-node-positive urothelial carcinoma of the bladder were treated by cystectomy and extended pelvic lymphadenectomy. Various lymph node parameters were determined separately for the three pelvic regions (external iliac, obturator and internal iliac). RESULTS: Of 4,080 evaluated lymph nodes (median 25 per patient, range 8-55) 39%, 35% and 26% (p<0.05) were found in the external iliac, obturator and internal iliac region, respectively. The distribution of the 625 lymph node metastases (median two per patient, range 1-35) was not significantly different between the regions (external iliac 33%, obturator 38%, internal iliac 29%). However, the median diameter of largest metastasis and total diameter of all metastases were smallest in the internal iliac region (external iliac 0.85 cm, 1.1 cm; obturator 0.8 cm, 1.0 cm; internal iliac 0.6 cm, 0.8 cm; p<0.03, p<0.05; for median diameter of largest metastasis and total diameter of all metastases, respectively). Metastases in only one region were found in 33% of patients (external iliac 13%, obturator 10%, internal iliac 10%); these three groups showed no significant difference in survival. No difference was detected in lymph node parameters between genders. CONCLUSIONS: Lymph node counts and retrieval of metastases depends on the extent of pelvic lymphadenectomy. Dissection not including the internal iliac region misses 26% of all pelvic lymph nodes, 29% of metastases, and understages a substantial number of patients as pN0 (10%). PMID- 20364030 TI - Focused assessment with sonography in trauma (FAST): should its role be reconsidered? AB - Focused assessment with sonography in trauma (FAST) is a limited ultrasound scan performed in the emergency department to assess patients admitted with blunt abdominal trauma (BAT). It is normally undertaken by emergency physicians in order to identify the presence of free fluid, which may represent haemoperitoneum. This potentially allows prompt referral to further imaging, such as a computed tomography (CT) scan, and/or surgery. FAST has been adopted worldwide, and most major trauma centres now have access to an ultrasound machine. Despite the popularity of FAST, there remains a lack of clarity and evidence around any actual contribution to patient survival. An ability to evaluate the true impact of FAST is complicated by factors such as the operator dependence of ultrasound, the improved access, speed and subsequent use of CT (which has reduced the value of FAST in some centres), a lack of standardisation around education and the most effective methods to ensure competence, and variations in the practice, quality and audit of FAST. Enthusiasm for FAST is undiminished among emergency physicians, and in general, point of care ultrasound is escalating in a range of areas, including the emergency department. Small portable and hand held ultrasound machines improve the accessibility of FAST and its benefits are frequently perceived to be an established and essential part of the emergency department service despite its limitations. Since the introduction of FAST, trauma patients are increasingly managed by non-surgical means if haemodynamically stable, and the presence of intraperitoneal fluid does not necessarily influence this decision. Recent developments in multi-detector CT, and in the use of contrast enhanced ultrasound, have broadened the management options for trauma patients, and can support a faster diagnostic pathway than was previously possible. FAST is a limited triage tool, whose actual value in the diagnostic and treatment pathway of patients with BAT remains questionable, and more data are needed to justify its use in the light of these recent developments. PMID- 20364031 TI - Free floating thrombus in the right heart causing pulmonary embolism. PMID- 20364032 TI - Time trends of female breast cancer mortality in Greece during 1980-2005: a population based study. AB - BACKGROUND: Changes in female breast cancer mortality trends have been observed in recent years in western countries. The aim of the present study was to analyse breast cancer mortality in Greece, between 1980 and 2005. METHODS: Time trends of breast cancer mortality were calculated per 100,000 women in the whole female population of Greece, in different age groups, and in different areas of the country. Mortality data and population age distribution were provided by the National Statistical Service of Greece. RESULTS: Overall, female breast cancer mortality in Greece had an increasing trend during 1980-2005. Subgroup analysis according to age showed that this increase was confined to women older than 70 years. In contrast, a mild decrease was noted after the mid-1990s in women 40-69 years old. There were no notable regional differences in breast cancer mortality. CONCLUSIONS: The increasing trend of breast cancer mortality in women aged 70 years and older could be attributed to limited use of secondary prevention methods and rare administration of systemic cytotoxic chemotherapy in these women. In contrast, implementation of these strategies could explain the recent reduction of breast cancer mortality in younger age groups. PMID- 20364033 TI - Using transactional analysis to improve clinical and educational supervision: the Drama and Winner's triangles. AB - The supervisor-trainee relationship is fundamental in ensuring the best continuing education for all trainees. One of the key skills of supervision is being able to communicate effectively; however, this is sometimes difficult. In this article we explore how two transactional analysis models, the Drama and Winner's triangles, can help supervisors work and communicate more effectively with trainees. All supervisors will have had a 'heartsink moment' before meeting a known trainee. The models can be used to explain these situations and what exactly is happening to the communication. The models provide methods of breaking free from these frustrating encounters and moving on with the relationship with your trainee. The models also help us understand the ways in which we can easily be pulled into games and offer insight into our own behaviours and relationships, not only with trainees, but also with patients, carers and colleagues. Real life scenarios are used throughout to explain the models. PMID- 20364034 TI - A case of transient hypertrophic cardiomyopathy. PMID- 20364035 TI - An intervention to decrease patient identification band errors in a children's hospital. AB - CONTEXT: Patient misidentification continues to be a quality and safety issue. There is a paucity of US data describing interventions to reduce identification band error rates. SETTING: Monroe Carell Jr Children's Hospital at Vanderbilt. KEY MEASURES: Percentage of patients with defective identification bands. STRATEGIES FOR CHANGE: Web-based surveys were sent, asking hospital personnel to anonymously identify perceived barriers to reaching zero defects with identification bands. Corrective action plans were created and implemented with ideas from leadership, front-line staff and the online survey. Data from unannounced audits of patient identification bands were plotted on statistical process control charts and shared monthly with staff. All hospital personnel were expected to "stop the line" if there were any patient identification questions. EFFECTS OF CHANGE: The first audit showed a defect rate of 20.4%. The original mean defect rate was 6.5%. After interventions and education, the new mean defect rate was 2.6%. LESSONS LEARNT: (a) The initial rate of patient identification band errors in the hospital was higher than expected. (b) The action resulting in most significant improvement was staff awareness of the problem, with clear expectations to immediately stop the line if a patient identification error was present. (c) Staff surveys are an excellent source of suggestions for combating patient identification issues. (d) Continued audit and data collection is necessary for sustainable staff focus and continued improvement. (e) Statistical process control charts are both an effective method to track results and an easily understood tool for sharing data with staff. PMID- 20364036 TI - Evidence in action--guidelines directing workload. AB - OBJECTIVE: To approximate the workload of blood pressure (BP) measurements and lifestyle counselling in primary healthcare when the related guidelines are followed. To evaluate the impact of facilitated guideline implementation with respect to workloads. DESIGN: Modelling study after cross-sectional audit process. SETTING: Thirty-one municipal health stations. Intervention Intrinsic facilitation in implementation of hypertension guideline. MAIN OUTCOME MEASURES: Number and level (normal <140/85 mmHg, slightly 140-160/85-95 mmHg or markedly elevated >160/95 mmHg) of BP measurements at nurses' appointments, approximation of time allocated for measurements and lifestyle counselling before and 1 year after the intervention. RESULTS: A total of 3119 BP measurements were recorded during the audit week in 2002. BP level measurements were "normal" in 1214 (38.9%), slightly elevated in 1371 (44.0%) and markedly elevated in 534 (17.1%). According to the modelling, 12% of a nurse's workday consisted of BP recordings and counselling. After intervention, the corresponding figures were 2330 measurements (828 (35.5%) normal, 990 (42.5%) slightly and 512 (22.0%) markedly elevated) corresponding to 6.3% of the workday. CONCLUSIONS: Through facilitation programmes, it is possible to change working practices according to the related guidelines, agree on the division of tasks and empower patients to engage with their own treatment. These changes can lead to considerable decreases in the workload of health centre personnel with consequent redistribution of personnel resources to patients in true need for services. PMID- 20364041 TI - Expression and significance of FXYD-3 protein in gastric adenocarcinoma. AB - OBJECTIVE: FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma. PATIENTS AND METHODS: FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n= 29) and gastric adenocarcinoma (n=51), obtained from surgical resection of gastric cancer patients. RESULTS: FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X;{2}=13.210, p < 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X;{2}=5.765, p=0.016). However, FXYD-3 expression was not correlated with patient's gender, age, tumor size, lymph node status and histological grade (p > 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma. PMID- 20364042 TI - Expression levels of Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) in primary breast carcinoma and distant breast cancer metastases. AB - INTRODUCTION: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. MATERIAL AND METHODS: Paraffin-embedded tissue of the primary and distant metastases (N=84) were collected and ALCAM immunohistochemistry was performed. RESULTS: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope=0.773, p < 0.001, r(2)= 0.504). CONCLUSION: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer. PMID- 20364043 TI - Expression of microRNAs in the urinary sediment of patients with IgA nephropathy. AB - BACKGROUND: Micro-RNAs (miRNAs) regulate one-third of all protein-coding genes and are fundamental in the pathophysiology of a wide range of diseases. We studied the expression of several miRNA species (miR-200 family, miR-205 and miR 192) in the urinary sediment of patients with IgA nephropathy (IgAN). METHODS: We studied 43 patients with biopsy-proven IgAN. Urinary expression of miRNAs was determined and compared to that from 13 healthy controls. RESULTS: The levels of urinary miR-200a, miR-200b and miR-429, but not miR-200c, miR-141, miR-205, or miR-192, were down-regulated in patients with IgAN. Proteinuria significantly correlated with urinary expression of miR-200a (r= -0.483, P < 0.001), miR-200b (r= -0.448, P=0.001) and miR-429 (r=-0.466, P=0.001). Baseline renal function significantly correlated with urinary expression of miR-200b (r= 0.512, P < 0.001) and miR-429 (r=0.425, P=0.005). Urinary gene expression of ZEB2 inversely correlated with miR-200b (r=-0.321, P=0.017); and vimentin expression inversely correlated with that of miR-200a (r=-0.360, P=0.007), miR-200b (r=-0.416, $P =$ 0.002) and miR-429 (r=-0.375, P=0.005). After 33.4 +/- 12.6 months, the rate of renal function decline significantly correlated with urinary expression of miR 200b (r=0.316, P=0.034). CONCLUSIONS: Urinary expression of miR-200a, miR-200b and miR-429 were down-regulated in patients with IgAN, and the degree of reduction correlated with disease severity and rate of progression. The results suggested that these miRNA species might play important roles in the pathophysiology of IgAN. Further studies are needed to clarify the role of urinary miRNA repression as a non-invasive marker of IgAN. PMID- 20364044 TI - Association of polymorphism in cytochrome P450 2D6 and N-acetyltransferase-2 with Parkinson's disease. AB - The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2}, that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6*2 (1749G/C and 2938C/T), CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2*7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95% CI: 0.56-54). No change was observed in the frequency of NAT*5 or NAT*6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6*4 or CYP2D6*10A(188C > T) and NAT2*5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD. PMID- 20364045 TI - Genetic variation of myeloperoxidase gene contributes to aggressive periodontitis: a preliminary association study in Turkish population. AB - Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes. It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis. The aim of this study was to explore the association between MPO-463G/A gene polymorphism and aggressive periodontitis (AgP) and chronic periodontitis (CP). The study included 147 subjects. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as the clinical parameters. Genomic DNA was obtained from the peripheral blood of 32 subjects with AgP, 25 with CP, and 90 reference controls. We genotyped the MPO-463G/A polymorphism using the PCR-RFLP method. All data were analyzed using SPSS version 13.0 for windows. There were no significant differences between the CP patients and controls regarding MPO-463A/G gene polymorphism either in terms of allele frequency or genotype frequency of MPO 463A/G. However, either in terms of allele frequency or genotype frequency of MPO 463A/G, there were significant differences between the AgP patients and the controls. In conclusion, our data suggest that MPO-463G/A may be associated with increased risk of aggressive periodontitis in Turkish patients. PMID- 20364046 TI - Coincidence of moderately elevated N-terminal pro-B-type natriuretic peptide, endothelial progenitor cells deficiency and propensity to exercise-induced myocardial ischemia in stable angina. AB - AIM: To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors - N-terminal pro-B type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia - in stable coronary artery disease (CAD) with preserved LV systolic function. METHODS: We studied 30 non-diabetic men with one vessel CAD, LV ejection fraction 60% and normal LV diastolic function (n=16) or impaired LV relaxation (by ultrasound including tissue Doppler) (n=14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry. RESULTS: CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP-CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score. CONCLUSIONS: Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors. PMID- 20364048 TI - The celebration of the 20th anniversary of WORK. PMID- 20364047 TI - CD14CD16 monocyte subset levels in heart failure patients. AB - Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF) patients, to verify whether increased severity of CHF is linked to the expansion of specific monocyte subsets, and finally to investigate the relationship between monocyte subset relative frequencies, laboratory parameters of inflammation, and monocyte ACE expression. Thirty consecutive CHF patients and 26 healthy control subjects were evaluated for peripheral blood monocyte expression of CD14, CD16 and CD143 (ACE) by flow cytometry, and for endothelial-derived soluble CD146 levels by ELISA. CD14++ CD16+ frequency was significantly higher in CHF patients than in Controls (%, median value and IQ) (12.3, 8.7-14.8 vs 5.9, 4.7-6.9, p< 0.05, CHF vs Controls), and it increased depending on how high NYHA class was, on worsening LV ejection fraction and on circulating pro-BNP values. Furthermore, it was associated with increasing creatinine and with decreasing GFR and albumin levels. Monocyte CD143 expression was significantly elevated in CHF patients as compared to Controls, and positively associated with CD14++ CD16+ levels. Frequencies of CD14+ CD16+ monocytes were significantly lower in CHF patients as compared to Controls, and negatively correlated with levels of soluble CD146 (r=-0.529; p 0.048). In conclusion, monocytic CD14++ CD16+ frequency and CD143 levels are increased and reflect disease status and progressive cardiac deterioration in CHF patients. The CD14+ CD16+ subset is depleted in CHF and is linked to endothelial damage in this group of patients. Although the question of whether differences in monocyte CD14CD16 expansion are causal or whether they represent a marker of HF progression which is potentially relevant for risk prediction remains unanswered, we believe that our data represent an important tool for exploring the role of selective inflammatory pathways in CHF progression. PMID- 20364049 TI - WORK: a historical evaluation of the impact and evolution of its editorial board. AB - OBJECTIVES: A historical review of the editorial board and the founding editor of WORK: A Journal of Prevention, Assessment and Rehabilitation was conducted to examine the understanding of the editorship and contributions of this team to the knowledge in WORK. PARTICIPANTS: The team of four authors worked together to identify an approach to evaluate the contributions and impact of WORK's editorial board (EB) on the journal's scholarship. The editor-in-chief (EIC) and editorial board members were participants in this evaluation. METHODS: Informative and formative evaluations were used to investigate how knowledge was shaped through the development of an epistemic community of scholars in the field of work. Metrics of the EB composition and participation in the journal as well as surveys and interviews with the board and the editor-in-chief were analyzed. RESULTS: The EB represents an international community of scholars with a common interest in work and who contribute academically both within WORK and beyond. The epistemic community that has evolved through the editorial board represents a pluralistic perspective on work that is needed to inform practice, and knowledge. CONCLUSION: Future directions to continue to advance knowledge through WORK's editorial board and EIC are elaborated. PMID- 20364050 TI - Twenty years of assessment in WORK: a narrative review. AB - INTRODUCTION: The aim of this review was to gain an understanding of the first 20 years of contributions to WORK within the assessment domain and to reflect on the perspectives underscoring this knowledge base. METHOD: A narrative review of assessment articles using the WORK ARTicle database was conducted. Assessment articles were searched using issues from 1990 to 2009. Descriptive data was analyzed to examine historical trends of the specific types and dimensions of articles, the regional location of the contributions, and the methodological accordance. A reflective process was used by an editorial board member of WORK to inductively interpret perspectives and contextual issues that underpinned the evolution of the assessment domain in WORK. RESULTS: Over half of $N=$ 108 of the articles on assessment in WORK focused on establishing or reporting reliability and validity of assessments used in clinical practice or evaluation research. The majority of the assessment articles were predominantly focused on the person. Contributions of articles were from 5 regions: North America, Europe, Australia, Asia and Africa. CONCLUSIONS: Assessment articles in WORK have contributed to the development of evidence to support assessment of the worker. These articles represent a knowledge base that emphasizes evidence-based assessments to evaluate what a person can and cannot do to participate in work. Efforts are needed to expand knowledge generation in assessment to include more evaluations on the workplace and occupation dimensions, and that also considers the worker in context. PMID- 20364051 TI - Perspectives on prevention, assessment, and rehabilitation of low back pain in WORK. AB - INTRODUCTION: The aim of this review was to describe the low back pain (LBP) knowledge base developed in WORK and to discuss its relevance to current perspectives in the broader literature on LBP and employment. METHOD: A scoping review of the literature in WORK on LBP and employment was conducted using published articles from 1990-2009. Articles were organized into geographical regions and summarized for contributions to the domains of WORK: prevention, assessment, and rehabilitation. Methodological accordance of the articles was also assessed. RESULTS: Fifty articles were extracted and organized into contributions from authors within North America (n=34) and outside North America (n=16). In total there were 26 prevention, 7 assessment, and 12 rehabilitation articles in this review. Five articles were also classified as 'understanding' articles. More than half of the articles retrieved employed quantitative methodology. CONCLUSIONS: WORK has contributed a broad realm of publications to the knowledge base on LBP and employment. Two thirds of the articles were contributed from authors within North America, with a greater emphasis on prevention. This article highlights the similarities and differences in the international knowledge base in the management of LBP in WORK. Future directions for research are elaborated drawing on current perspectives of two experts on the management of LBP. PMID- 20364052 TI - A scoping review of the knowledge base in WORK that addresses work related outcomes for individuals with chronic pain. AB - OBJECTIVE: Chronic pain such as arthritis has a significant impact on occupational performance in the workplace that contributes to decreased productivity, reduced rates of employment, personal and societal economic costs. In commemoration of the 20th anniversary of WORK, a scoping review was conducted to understand the knowledge base on chronic pain. The purpose of this was to examine and describe WORK's contribution to the literature relevant for rehabilitation professionals such as occupational therapists to improve work related outcomes for persons experiencing chronic pain. METHOD: The method employed the use of historical, citation and dimension analyses of assessment and intervention articles. RESULTS: Of the 30 articles identified in WORK, the historical analysis of their scope indicated an international representation of authors and a greater emphasis on quantitative study designs. The citation analysis revealed that the articles in WORK drew heavily on medical literature to inform their studies. The dimensional analysis of the assessment and intervention articles applied an occupational lens of self-care, productivity and leisure, to draw upon the Occupational Competence Model and identified that the majority of papers focused on 2 or more dimensions of the person, environment and occupation. CONCLUSIONS: WORK has contributed to the knowledge base of assessment and intervention approaches that inform work rehabilitation strategies for individuals with chronic pain. To advance its knowledge base for the rehabilitation and management of chronic pain, WORK is encouraged to include more prevention and multidimensional interventions articles, as well as articles that contain multidimensional assessment tools that address both clinical and outcome assessments of chronic pain. Additionally internal dialogue should be encouraged within WORK so that new authors build on previous submissions and increase the impact and quality of research on chronic pain as it pertains to work. PMID- 20364053 TI - Advancing knowledge in work-related rehabilitation - review of research published in the journal of WORK. AB - OBJECTIVE: Many studies published in the journal WORK in the recent decades have discussed work and employment trends. However, the dimensions of these contributions over time have not been reviewed. The main objective of this study was to investigate the knowledge development in regard to work-related rehabilitation in WORK over the last two decades. METHODS: A scoping review was conducted using the following five stages: (i) identifying research question, (ii) identifying relevant studies, (iii) study selection, (iv) charting, summarizing, and collating the data, and (v) reporting the results. Studies were selected from the WORK ARTicle Database. RESULTS: Seventy-five relevant studies were identified. The findings reflect that WORK has published papers from across the world, with most of the studies from the United States, Sweden, Canada, and Hong Kong. The complexity and multi-factorial nature of work-related rehabilitation was reflected in the application of quantitative, qualitative, and mixed method research approaches, as well as case studies. Study participants were characterized by work, and non-work related injuries, systematic diseases/chronic illness, fulfilled certain socio-demographic characteristic, and represented various stakeholders. Fewer studies drew on secondary resources. In the findings one re-occurring theme has been noted: 'maintaining/obtaining/returning to secure and stable employment/work'. CONCLUSIONS: Four key-reflections evolved from this scoping review that provide potential avenues for future research. These key-reflections include (i) the national, transnational and international dimension of the reviewed studies, (ii) the various societal levels informing work-related rehabilitation practices, (iii) the diversity of methodologies applied in current research, and (iv) the variability of terminology used within the reviewed studies. The journal WORK has published a variety of research over the last two decades and contributed significantly to our current understanding of work-related rehabilitation. However, further research in these reflective areas would expand the current knowledge base. PMID- 20364054 TI - Best practices in the rehabilitation of acute musculoskeletal disorders in workers with injuries: an integrative review and analysis of evolving trends. AB - OBJECTIVE: Strategies for the restoration of function and job performance in workers with musculoskeletal disorders have changed considerably since industrial rehabilitation became a distinct specialization in the 1980s. A rich body of research concerning approaches to medical and rehabilitative management of these disorders exists, resulting in a large number of hybrid approaches worldwide. METHODS: This integrative review examined the evidence base for best practices in the rehabilitation of acute musculoskeletal workplace injuries, and also mapped the evolution of approaches over the past thirty years. Contextual factors that may have contributed to change were assessed through analysis of changing practice trends and review of descriptive literature over time. RESULTS: A clear movement away from simplistic, unidimensional approaches towards comprehensive workplace interventions is evident. Economic concerns and growing government and insurance regulation of workplace safety and injury management were the likely drivers of change. While the contributions of various elements of disability management in the workplace were examined, many features of onsite interventions remain to be examined. CONCLUSIONS: A strong body of research has produced notable advances in management of acute musculoskeletal workplace injury. Research concerning the delivery of workplace-based interventions, the role of workplace environment factors and a range of worker outcomes will further advance knowledge in this field. PMID- 20364055 TI - Ergonomic interventions for office workers with musculoskeletal disorders: a systematic review. AB - INTRODUCTION: Ergonomic interventions designed for office and computer work have become widely available and heavily marketed but there is little evidence to support their use with workers who already have a musculoskeletal disorder (MSD). The purpose of any ergonomic intervention can be to improve worker comfort, safety and/or productivity. The ergonomic research in secondary prevention typically focuses outcomes on improved worker comfort but less if any emphasis has been put on productivity and safety. The purpose of this study was to determine the level and quality of evidence supporting ergonomic interventions to improve the comfort, safety and/or productivity of office workers with symptoms of MSDs. METHOD: A search of the ergonomic intervention literature based on MSDs of four body areas (low back, upper limb, eye and neck) was employed. The studies underwent two levels of analysis for inclusion in a best-evidence synthesis approach, which included a priori evaluation of specific interventions relative to outcomes of comfort, safety and/or productivity. RESULTS: Twenty-seven out of 202 articles were synthesized based on relevance, quality and significant results. Only 8 articles were determined high quality and no strong levels of evidence were identified. Levels of evidence for specific ergonomic interventions ranged from insufficient to moderate. Generally outcomes were focused mostly on improved comfort of workers. CONCLUSIONS: There is still limited quality research that addresses ergonomic interventions designed for secondary prevention. Further high quality studies are needed to support evidence-based ergonomic interventions in practice. For all stakeholders to fully evaluate the usefulness of the ergonomic intervention studies need to attend to outcomes not only of worker comfort but also to productivity and safety. PMID- 20364056 TI - A systematic review of multidisciplinary outcomes in the management of chronic low back pain. AB - OBJECTIVE: Previous research has provided an inconsistent message as to the effectiveness of multidisciplinary programs to improve employment outcomes in clients with Chronic Low Back Pain (CLBP). The primary aims of this review were to: 1) update the evidence for the multidisciplinary treatment of CLBP to improve employment outcomes 2) assess what knowledge supports occupational therapy as contributing to a multidisciplinary approach in the treatment of CLBP. PARTICIPANTS: Working-age adults experiencing CLBP who took part in controlled trials evaluating multidisciplinary programs between July 1998 and July 2009. METHODS: Updated guidelines provided by the Cochrane Collaboration Back Review Group (BRG) were used to perform a systematic review to identify, appraise, and synthesize research evidence relevant to our research questions. RESULTS: Twelve unique articles were found, after a database search and citation tracking, only two of which were high quality. Our findings suggest that there is still conflicting evidence for the effectiveness of multidisciplinary programs to improve employment outcomes in CLBP. CONCLUSIONS: The results are discussed with reference to current methodological limitations found in the literature. Furthermore, occupational therapists were found to be underutilized in the included studies and future multidisciplinary programs should take advantage of the wide range of skills that occupational therapists can contribute in this practice area. PMID- 20364057 TI - A systematic review of chiropractic management of adults with Whiplash-Associated Disorders: recommendations for advancing evidence-based practice and research. AB - The literature relevant to the treatment of Whiplash-Associated Disorders (WAD) is extensive and heterogeneous. METHODS: A Participatory Action Research (PAR) approach was used to engage a chiropractic community of practice and stakeholders in a systematic review to address a general question: 'Does chiropractic management of WAD clients have an effect on improving health status?' A systematic review of the empirical studies relevant to WAD interventions was conducted followed by a review of the evidence. RESULTS: The initial search identified 1,155 articles. Ninety-two of the articles were retrieved, and 27 articles consistent with specific criteria of WAD intervention were analyzed in depth. The best evidence supporting the chiropractic management of clients with WAD is reported. Further review identified ways to overcome gaps needed to inform clinical practice and culminated in the development of a proposed care model: the WAD-Plus Model. CONCLUSIONS: There is a baseline of evidence that suggests chiropractic care improves cervical range of motion (cROM) and pain in the management of WAD. However, the level of this evidence relevant to clinical practice remains low or draws on clinical consensus at this time. The WAD-Plus Model has implications for use by chiropractors and interdisciplinary professionals in the assessment and management of acute, subacute and chronic pain due to WAD. Furthermore, the WAD-Plus Model can be used in the future study of interventions and outcomes to advance evidence-based care in the management of WAD. PMID- 20364058 TI - Narrative reflections on occupational transitions. PMID- 20364059 TI - Using scoping literature reviews as a means of understanding and interpreting existing literature. AB - OBJECTIVE: This article compares and contrasts scoping literature reviews with other established methods for understanding and interpreting extant research literature. METHODS: Descriptions of the key principles and applications of scoping reviews are illustrated with examples from contemporary publications. CONCLUSIONS: Scoping reviews are presented as an efficient way of identifying themes and trends in high-volume areas of scientific inquiry. PMID- 20364061 TI - Sickle cell disease: selected aspects of pathophysiology. AB - Sickle cell disease (SCD), a genetically-determined pathology due to an amino acid substitution (i.e., valine for glutamic acid) on the beta-chain of hemoglobin, is characterized by abnormal blood rheology and periods of painful vascular occlusive crises. Sickle cell trait (SCT) is a typically benign variant in which only one beta chain is affected by the mutation. Although both SCD and SCT have been the subject of numerous studies, information related to neurological function and transfusion therapy is still incomplete: an overview of these areas is presented. An initial section provides pertinent background information on the pathology and clinical significance of these diseases. The roles of three factors in the clinical manifestations of the diseases are then discussed: hypoxia, autonomic nervous system regulation and blood rheology. The possibility of a causal relationship between these three factors and sudden death is also examined. It is concluded that further studies in these specific areas are warranted. It is anticipated that the outcome of such research is likely to provide valuable insights into the pathophysiology of SCD and SCT and will lead to improved clinical management and enhanced quality of life. PMID- 20364062 TI - Role of plasma proteins in whole blood viscosity: a brief clinical review. AB - Whole blood viscosity is affected by a number of factors, among which plasma proteins are a major component. They exert their effects either directly or through their influence on red cell aggregation. Changes in fibrinogen and in immunoglobulins, under both physiologic and pathologic conditions can increase whole blood viscosity. Blood flow through the microvasculature is impaired when viscosity increases, leading to tissue ischemia and a syndrome complex usually referred to as the hyperviscosity syndrome. Abnormalities of fibrinogen greatly increase its ability to cause red cell aggregation, and is a contributory pathogenic factor in ischemic heart disease and stroke. Immunoglobulins may affect blood viscosity directly, or by increasing the red cell aggregation. Changes are seen in many clinical disorders, ranging from inflammatory diseases to plasma cell dyscrasias. The clinical manifestations may be mild and often unnoticed, or they may be life threatening requiring emergency plasmapheresis. Proper management requires a clear understanding of the underlying pathology. When the symptom complex indicates a high probability of the hyperviscosity syndrome, it should lead to early diagnosis and treatment. Therapeutic approaches should include both removing the abnormal plasma protein and treating the primary cause. PMID- 20364063 TI - Viscosity of human bile sampled from the common bile duct. AB - Cholestasis is a frequent gastroenterological problem, which is tackled by endoscopic procedures. Little is known about bile viscosity, a major determinant of its flow. We measured the viscosity of bile from the common bile duct during endoscopic retrograde cholangiography. Bile was aspirated immediately after cannulation of the papilla and deep-frozen. Viscosity was measured with a rotational viscometer at 37 degrees C and a broad range of shear rates (0.08-69.5 s(-1)). The majority of the 138 patients (64.5%) had bile viscosities between water (0.7 mPa.s) and the lower limit of plasma (1.1 mPa.s). In 20 patients (14.5%) it was above that of plasma (>1.4 mPa.s), and showed a non-Newtonian behaviour, i.e. the viscosity increased exponentially with decreasing shear rate. Cholecystectomized patients had a lower bile viscosity. Bile viscosities did not differ between patient groups with either choledocholithiasis, sludge, cholangitis, biliary pancreatitis, pancreatic carcinoma, or cholangiocarcinoma. We conclude that bile viscosity in the common bile duct is usually lower than that of plasma, in 15% it is higher and increases exponentially with decreasing flow rate, which may lead to a vicious cycle. PMID- 20364064 TI - Relationship between C-reactive protein and early activation of leukocytes indicated by leukocyte antisedimentation rate (LAR) in patients with acute cerebrovascular events. AB - The purpose of this study was to determine the relationship between high sensitive C-reactive protein (hsCRP) and leukocyte antisedimentation rate (LAR) as a specific test to detect early activation of leukocytes providing the first line of defence against infections in ischemic stroke. In 49 patients with acute ischemic events and 61 healthy subjects (HS), we examined LAR, astroglia specific S100B indicating the extent of brain tissue damage and hsCRP within 6 hours, as well as 24 and 72 hours after onset of symptoms. Serum levels of hsCRP on admission was significantly higher in patients with acute ischemic stroke (AIS) compared to HS and were higher in patients with recurrent to first ever ischemic stroke. Increased basal levels of hsCRP also correlated with severity of stroke and extent of infarct reflected by S100B levels in sera, but did not correlate with post-stroke infections. However, a higher rate of infection was observed among patients, in whom hsCRP was elevated at 72 hours but LAR did not increase. Therefore, such late elevation of hsCRP may indicate pre-clinical infections due to deficient leukocyte activation. Simple tests like LAR and hsCRP may help in predicting outcome and high risk of infectious complications. PMID- 20364065 TI - Adenosine transport, erythrocyte deformability and microvascular dysfunction: an unrecognized potential role for dipyridamole therapy. AB - Reperfusion injury and no-reflow phenomenon are known entities that contribute to persistent impairment in myocardial perfusion and regional myocardial dysfunction following restoration of epicardial coronary blood flow after a myocardial infarction. Following prolonged ischemia, oxidative stress and inflammation mediated alterations in erythrocyte mechanics and microvascular architecture play a major role in ischemia/reperfusion injury and no-reflow phenomenon. An increase in red cell rigidity is an important rheological aspect of RBCs, which facilitates platelet aggregation with the subendothelium. Dipyridamole inhibits the reuptake of adenosine which causes platelet inhibition and vasodilatation. Dipyridamole improves microvascular function by increasing RBC deformability and reducing blood viscosity. In addition, it has anti-oxidant and anti-inflammatory properties that provide protection to the microvasculature. This review discusses the potential role for dipyridamole therapy in the treatment of microvascular dysfunction. PMID- 20364066 TI - Acute dichlorvos poisoning induces hemorheological abnormalities in rabbits via oxidative stress. AB - Dichlorvos is an important insecticide used largely. Some studies have demonstrated that organophosphate pesticide has effects on erythrocyte membrane structures, which is critical to erythrocyte function and hemorheology. The aim of the present study was to explore the effect of oxidative stress on hemorheological changes during dichlorvos poisoning in rabbits. Data indicated that after dichlorvos exposure the hematocrit adjusted viscosity at high shear rate increased and erythrocyte membrane fluidity decreased. Data obtained from plasma showed that lipid peroxidative substance-malonaldehyde was elevated and superoxide dismutase was reduced. In summary, oxidative stress does occur in dichlorvos poisoning and may lead to hemorheological alterations. The changes of hemorheology may be responsible for the pathophysiology of the dichlorvos poisoning. PMID- 20364067 TI - Effect of Ligaria cuneifolia catechin- and quercetin-enriched fractions on hemorheology and plasma cholesterol. AB - We tested the in vivo and the in vitro effects of both Ligaria cuneifolia catechin- and quercetin-enriched fractions on erythrocyte shape and deformability, and on plasma cholesterol level. For in vivo studies, adult male Wistar rats were randomized in three experimental groups which received intraperitoneally, once a day, 3 days: CONTROL: saline solution (C; n = 6); catechin from L. cuneifolia, 0.60 mg/100 g body weight (CLc; n = 6), or quercetin from L. cuneifolia, 2.3 mg/100 g body weight (QLc; n = 6). For in vitro studies, blood samples obtained from male Wistar rats were divided into three fractions, which were incubated with saline solution (C), catechin (CLc; n = 5) and quercetin (QLc; n = 5), in a concentration equivalent to 0.60 mg/100 g body weight, and 2.3 mg/100 g body weight, respectively. CLc significantly reduced the rigidity index due to a diminished mean concentration volume. QLc induced erythrocyte rigidization (less deformability), thus increasing blood viscosity. Neither of the two treatments produced any changes in plasmatic or biliary excretion of cholesterol. Opposite results were observed in rigidity index with CLc and QLc. In vitro studies showed an interaction of both CLc and QLc with the erythrocyte membrane, which induced changes in the erythrocyte shape from discocyte to stomatocyte. PMID- 20364068 TI - In vitro hemorheological effects of red wine and alcohol-free red wine extract. AB - The French paradox is based on epidemiological evidence which supports that moderate red wine consumption reduces the risk of cardiovascular diseases. A number of experimental animal studies reported favourable cardiovascular effects of alcohol-free red wine extract (AFRW). Our study was designed to determine red wine and AFRW induced changes in various hemorheological parameters. These effects may play a role in the pathophysiology of the French paradox regarding the cardiovascular protective impacts of red wine. Blood samples of healthy volunteers were mixed with red wine to achieve alcohol concentrations of 1 per thousand, 3 per thousand and 10 per thousand, respectively, with equivalent amount of AFRW or physiological saline. Blood samples were pretreated with red wine or AFRW in order to prove the protective effects on erythrocytes from impairment of deformability caused by the free radical generator phenazine methosulfate (PMS). Erythrocyte aggregation (Myrenne and LORCA), deformability (LORCA) and platelet aggregation (Carat TX4) were measured. Erythrocyte aggregation using Myrenne aggregometer was inhibited by red wine and AFRW compared to the saline treated samples. The difference reached already significance at 1 per thousand concentration at the AFRW samples (p < 0.05). Furthermore, red wine caused stronger inhibition than AFRW. The difference between the two agents became significant at 10 per thousand concentration (p < 0.05). LORCA aggregation index and threshold shear rate supported these results at the highest concentration. Erythrocyte deformability of healthy volunteers did not change significantly for any concentrations of red wine and AFRW. On the other hand AFRW at 3 per thousand concentration significantly prevented erythrocytes from impairment of deformability caused by PMS (p < 0.05). Platelet aggregation was significantly inhibited by the highest concentration of AFRW (p < 0.05). Our results show that red wine and AFRW have some beneficial effects on hemorheological parameters that may contribute to the French paradox. PMID- 20364069 TI - A peptide antagonist of the ErbB1 receptor inhibits receptor activation, tumor cell growth and migration in vitro and xenograft tumor growth in vivo. AB - The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in tumorigenesis and cancer disease progression, and therefore has become an attractive target for structure-based drug design. ErbB receptors are activated by ligand-induced homo- and heterodimerization. Structural studies have revealed that ErbB receptor dimers are stabilized by receptor-receptor interactions, primarily mediated by a region in the second extracellular domain, termed the "dimerization arm". The present study is the first biological characterization of a peptide, termed Inherbin3, which constitutes part of the dimerization arm of ErbB3. Inherbin3 binds to the extracellular domains of all four ErbB receptors, with the lowest peptide binding affinity for ErbB4. Inherbin3 functions as an antagonist of epidermal growth factor (EGF)-ErbB1 signaling. We show that Inherbin3 inhibits EGF-induced ErbB1 phosphorylation, cell growth, and migration in two human tumor cell lines, A549 and HN5, expressing moderate and high ErbB1 levels, respectively. Furthermore, we show that Inherbin3 inhibits tumor growth in vivo and induces apoptosis in a tumor xenograft model employing the human non-small cell lung cancer cell line A549. The Inherbin3 peptide may be a useful tool for investigating the mechanisms of ErbB receptor homo- and heterodimerization. Moreover, the here described biological effects of Inherbin3 suggest that peptide-based targeting of ErbB receptor dimerization is a promising anti-cancer therapeutic strategy. PMID- 20364070 TI - In vitro effects of oestrogens, antioestrogens and SERMs on pancreatic solid pseudopapillary neoplasm-derived primary cell culture. AB - BACKGROUND: Solid-pseudopapillary neoplasms of the pancreas (SPNs) are uncommon tumours usually frequent in young women. Although the pathogenesis of SPNs is uncertain a potential influence of the sex hormone milieu on the biology of these tumours has been suggested. The controversial expression of oestrogen receptors (ERs) in SPNs, provide a rationale for studying the effects of oestrogenic molecules on SPN development. METHODS: The expression of a large series of hormonal ligands and receptors was evaluated in tissue specimens and in a primary cell culture (SPNC), obtained from a SPN in young female patient. The effects of 17beta-oestradiol (17betaE2), ICI 182,780 and tamoxifen (Tam) on cell replication and growth were examined. RESULTS: We have established SPNC primary line. Immunocytochemical analysis was positive for vimentin, cyclin D1 and beta-catenin and negative for cytokeratin, CD10 and neuroendocrine markers, in line with the immunostaining features of the tumoral tissue. Expression of ERalpha, ERbeta and progesterone mRNAs was demonstrated in SPNC and tumor tissue. A proliferative and antiproliferative action of 17betaE2 and Tam respectively were proved in SPNC. CONCLUSION: In conclusion, we provide the first direct evidence that oestrogenic molecules can influence proliferation of SPNC, offering future strategies in the control of this neoplasia via selective ER modulators. PMID- 20364071 TI - Transformation through partnerships. PMID- 20364074 TI - "Girls take charge": a community-based participatory research program for adolescent girls. AB - BACKGROUND: Adolescent females are at high risk for health disparities. An approach to minimizing health disparities involves facilitating changes in the environment within the community. Community-based participatory research (CBPR) is an important method of producing community change. OBJECTIVES: The objectives were for adolescent females to learn the CBPR process, implement a community health change project, and build capacity by engaging community agencies. METHODS: After conducting an assessment of community problems, the adolescents formed a coalition of community partners and implemented a Lead Poisoning Awareness Fair and a "lock-in" to educate about child maltreatment. A pre- and post-test research design was used. RESULTS: The community changes that resulted were policy change for routine lead testing, a DVD about child maltreatment, and care packages for adolescent mothers. Modest increases in knowledge about lead poisoning and child maltreatment occurred. CONCLUSION: Adolescent females were successful in using CBPR to produce positive community changes. PMID- 20364073 TI - Translating diabetes prevention into native Hawaiian and Pacific Islander communities: the PILI 'Ohana Pilot project. AB - BACKGROUND: Native Hawaiians (NH) and Other Pacific Islanders (OPI) bear an excess burden of diabetes health disparities. Translation of empirically tested interventions such as the Diabetes Prevention Program Lifestyle Intervention (DPP LI) offers the potential for reversing these trends. Yet, little is known about how best to translate efficacious interventions into public health practice, particularly among racial/ethnic minority populations. Community-based participatory research (CBPR) is an approach that engages the community in the research process and has recently been proposed as a means to improve the translation of research into community practice. OBJECTIVES: To address diabetes health disparities in NHOPIs, CBPR approaches were used to: (1) culturally adapt the DPP-LI for NHOPI communities; and (2) implement and examine the effectiveness of the culturally-adapted program to promote weight loss in 5 NHOPI communities. METHODS: Informant interviews (n=15) and focus groups (n=15, with 112 NHOPI participants) were completed to inform the cultural adaptation of the DPP-LI program. A team of 5 community investigators and 1 academic research team collaboratively developed and implemented the 12-week pilot study to assess the effectiveness of the culturally adapted program. RESULTS: A total of 127 NHOPIs participated in focus groups and informant interviews that resulted in the creation of a significantly modified version of the DPP-LI, entitled the PILI 'Ohana Lifestyle Intervention (POLI). In the pilot study, 239 NHOPIs were enrolled and after 12 weeks (post-program), mean weight loss was -1.5 kg (95%CI 2.0, -1.0) with 26% of participants losing > or = 3% of their baseline weight. Mean weight loss among participants who completed all 8 lessons at 12 weeks was significantly higher (-1.8 kg, 95%CI -2.3, -1.3) than participants who completed less than 8 lessons (-0.70 kg, 95%CI -1.1, -0.29). CONCLUSION: A fully engaged CBPR approach was successful in translating an evidence based diabetes prevention program into a culturally relevant intervention for NHOPI communities. This pilot study demonstrates that weight loss in high risk minority populations can be achieved over a short period of time using CBPR approaches. PMID- 20364075 TI - Salud de la mujer: using fotonovelas to increase health literacy among Latinas. AB - BACKGROUND: There is an identified need for health literacy strategies to be culturally sensitive and linguistically appropriate. OBJECTIVES: The goal of our community-based participatory research (CBPR) project related to health and nutrition is to demonstrate that active community involvement in the creation of health education fotonovelas that are relevant to culture, ethnicity, gender, social class, and language can increase the health literacy of women in a disadvantaged community. METHODS: We recruited 12 women to take part in our pilot fotonovela intervention about healthy eating and nutrition. Pre- and post-test assessments of knowledge, attitudes, and behavior around nutrition were given at baseline and will be collected after the completion of the project. RESULTS: We hypothesize that post-test assessments of our participants will reveal increased nutrition knowledge as well as positive changes in attitudes and behavior toward healthy eating. CONCLUSIONS: We believe that our fotonovelas will represent experiences of community members and encourage good health practices by increasing knowledge and cooperation among community members. PMID- 20364076 TI - Building an international collaboration on participatory health research. AB - THE PROBLEM: Participatory health research (PHR) is receiving increased international attention as an approach for addressing various health issues. However, PHR has not yet achieved the status of other forms of research in terms of having an impact on health policy decisions. PURPOSE OF ARTICLE: This article reports on the current status of the new International Collaboration on Participatory Health Research (ICPHR). KEY POINTS: By formulating common definitions and standards for PHR and synthesizing the results and methods of participatory research, the collaboration will seek to strengthen the role of PHR in academic and political institutions. CONCLUSION: The collaboration is an important structure for advancing the practice, theory, and impact of PHR internationally. PMID- 20364077 TI - Applying community-based participatory research principles and approaches in clinical trials: forging a new model for cancer clinical research. AB - Although an estimated 20% of adult cancer patients are medically eligible for a cancer treatment clinical trial (CCT), adult trial participation in the U.S. remains under 3%.- Participation rates are even lower among ethnic and racial minorities and the medically underserved, who tend to have higher cancer mortality rates than the population as a whole.- Given persistent cancer health disparities in these populations, cancer clinical trial participation is increasingly an issue of social justice. Community-based participatory research (CBPR) approaches have been repeatedly recommended as a key strategy for increasing and diversifying cancer clinical trial participation and enhancing their relevance and quality. In 2006, Community-Campus Partnership for Health (CCPH) and the Education Network to Advance Cancer Clinical Trials (ENACCT) received funding from the Agency for Healthcare Research and Quality and the National Cancer Institute (NCI), along with industry and nonprofit partners, to develop the first set of national recommendations to employ CBPR approaches in multisite, phase III cancer clinical trials. The Communities as Partners in Cancer Clinical Trials: Changing Research, Practice and Policy final report, developed through a national advisory committee, two stakeholder meetings and a public vetting process, makes more than fifty detailed recommendations to engage communities in specific and meaningful ways throughout the cancer clinical trial process.1 The report is the first to provide specific guidance as to how and why clinical trials should involve communities affected by cancer-from trial design to implementation to dissemination of results. This paper describes the background and rationale for the initiative, the process used to develop and disseminate the report, and the challenges and opportunities for implementing the report's community-based approaches to cancer clinical research. PMID- 20364079 TI - A participatory method to identify root determinants of health: the heart of the matter. AB - BACKGROUND: Co-learning is one of the core principles of community-based participatory research (CBPR). Often, it is difficult to engage community members beyond those involved in the formal partnership in co-learning processes. However, to understand and address locally relevant root factors of health, it is essential to engage the broader community in participatory dialogues around these factors. OBJECTIVE: This article provides a glimpse into how using a photo elicitation process allowed a community-academic partnership to engage community members in a participatory dialogue about root factors influencing health. The article details the decision to use photo-elicitation and describes the photo elicitation method. METHOD: Similar to a focus group process, photo-elicitation uses photographs and questions to prompt reflection and dialogue. Used in conjunction with an economic development framework, this method allows participants to discuss underlying, or root, community processes and structures that influence health. CONCLUSION: Photo-elicitation is one way to engage community members in a participatory dialogue that stimulates action around root factors of health. To use this method successfully within a CBPR approach, it is important to build on existing relationships of trust among community and academic partners and create opportunities for community partners to determine the issues for discussion. PMID- 20364080 TI - Expanding the chronic care framework to improve diabetes management: the REACH case study. AB - BACKGROUND: Reducing the burden of chronic conditions among minorities requires novel approaches to prevent and manage disease. OBJECTIVES: This paper describes the expansion of the Chronic Care Model (CCM) to include a community focus for improving diabetes self-management and reducing health disparities. METHODS: The literature review assesses the concept of "community" in improving outcomes as viewed by proponents of the CCM for chronic disease. The CCM was then modified and informed by experiences of a major community-based participatory action initiative to improve diabetes outcomes, the Racial and Ethnic Approaches to Community Health (REACH) Charleston and Georgetown Diabetes Coalition. RESULTS: Based on our experiences with community-based and health systems diabetes interventions, we present examples of improvements within both health delivery practice sites and other community systems that are essential for improving diabetes outcomes and reducing disparities. Building on the Centers for Disease Control and Prevention's (CDC) principles of community involvement, our coalition activities provide examples of working with community partners to frame this enhanced ecologically grounded Community CCM (CCCM). CONCLUSION: The resulting CCCM integrates expanded conceptual frameworks, evidence-based practice, community-based evidence and participatory actions, and highlights the possibilities and challenges for improving chronic disease outcomes and reducing disparities via community programs that foster individual, systems, community, and policy change. PMID- 20364081 TI - Launching native health leaders: students as community-campus ambassadors. AB - BACKGROUND: Ancient teaching styles such as storytelling can help Native students to navigate the educational pipeline, and become forces for shaping health and research landscapes. Many experience isolation on campuses where these worldviews are marginalized. OBJECTIVE: Launching Native Health Leaders (LNHL) reduces academic isolation by creating an environment where students identify with Native values while exposing them to health and research career opportunities and interdisciplinary professional and community networks. Student experiences and the LNHL mentoring approach are described through phases of the Hero's Journey, a universal mythic story of human struggle and transformation. METHODS: Undergraduates were recruited to attend health and research conferences through college and university student service programs. Tribal community representatives led group discussions focused on tribal health issues, and students explored intersections of indigenous knowledge with community-based participatory research (CBPR) and their educational journeys. RESULTS: LNHL supported more than sixty students to attend eight professional conferences since 2006 that included themes of cancer control, tribal wellness, and indigenous knowledge systems for health. Students pursuing higher degrees and community service careers participated in conference sessions, small group discussions, and reflection activities with professional and tribal community mentors. CONCLUSION: Mainstream academic systems must include indigenous voices at all levels of leadership to shift the direction of health trends. LNHL builds capacity for community-based efforts by balancing Indigenous and academic mentoring and empowering Native students to navigate their personal journeys and create pathways to serve the needs of Indigenous peoples. Students from other marginalized groups may benefit from an LNHL mentoring approach. PMID- 20364082 TI - Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. AB - The lymphatic system plays a key role in tissue fluid homeostasis. Lymphatic dysfunction contributes to the pathogenesis of many human diseases, including lymphedema and tumor metastasis. However, the mechanisms regulating lymphangiogenesis remain largely unknown. Here, we show that COUP-TFII (also known as Nr2f2), an orphan member of the nuclear receptor superfamily, mediates both developmental and pathological lymphangiogenesis in mice. Conditional ablation of COUP-TFII at an early embryonic stage resulted in failed formation of pre-lymphatic ECs (pre-LECs) and lymphatic vessels. COUP-TFII deficiency at a late developmental stage resulted in loss of LEC identity, gain of blood EC fate, and impaired lymphatic vessel sprouting. siRNA-mediated downregulation of COUP TFII in cultured primary human LECs demonstrated that the maintenance of lymphatic identity and VEGF-C-induced lymphangiogenic activity, including cell proliferation and migration, are COUP-TFII-dependent and cell-autonomous processes. COUP-TFII enhanced the pro-lymphangiogenic actions of VEGF-C, at least in part by directly stimulating expression of neuropilin-2, a coreceptor for VEGF C. In addition, COUP-TFII inactivation in a mammary gland mouse tumor model resulted in inhibition of tumor lymphangiogenesis, suggesting that COUP-TFII also regulates neo-lymphangiogenesis in the adult. Thus, COUP-TFII is a critical factor that controls lymphangiogenesis in embryonic development and tumorigenesis in adults. PMID- 20364083 TI - Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. AB - In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPARgamma coactivator-1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity and fatty acid oxidation genes in preference for glucose metabolism pathways. Interestingly, despite the reduced PGC-1 activity, these pathological stressors are associated with mitochondrial biogenesis, at least initially. The transcription factors that regulate these changes in the setting of reduced PGC-1 are unknown, but Myc can regulate glucose metabolism and mitochondrial biogenesis during cell proliferation and tumorigenesis in cancer cells. Here we have demonstrated that Myc activation in the myocardium of adult mice increases glucose uptake and utilization, downregulates fatty acid oxidation by reducing PGC-1alpha levels, and induces mitochondrial biogenesis. Inactivation of Myc in the adult myocardium attenuated hypertrophic growth and decreased the expression of glycolytic and mitochondrial biogenesis genes in response to hemodynamic load. Surprisingly, the Myc-orchestrated metabolic alterations were associated with preserved cardiac function and improved recovery from ischemia. Our data suggest that Myc directly regulates glucose metabolism and mitochondrial biogenesis in cardiac myocytes and is an important regulator of energy metabolism in the heart in response to pathologic stress. PMID- 20364084 TI - Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. AB - Glutaredoxin 5 (GLRX5) deficiency has previously been identified as a cause of anemia in a zebrafish model and of sideroblastic anemia in a human patient. Here we report that GLRX5 is essential for iron-sulfur cluster biosynthesis and the maintenance of normal mitochondrial and cytosolic iron homeostasis in human cells. GLRX5, a mitochondrial protein that is highly expressed in erythroid cells, can homodimerize and assemble [2Fe-2S] in vitro. In GLRX5-deficient cells, [Fe-S] cluster biosynthesis was impaired, the iron-responsive element-binding (IRE-binding) activity of iron regulatory protein 1 (IRP1) was activated, and increased IRP2 levels, indicative of relative cytosolic iron depletion, were observed together with mitochondrial iron overload. Rescue of patient fibroblasts with the WT GLRX5 gene by transfection or viral transduction reversed a slow growth phenotype, reversed the mitochondrial iron overload, and increased aconitase activity. Decreased aminolevulinate delta, synthase 2 (ALAS2) levels attributable to IRP-mediated translational repression were observed in erythroid cells in which GLRX5 expression had been downregulated using siRNA along with marked reduction in ferrochelatase levels and increased ferroportin expression. Erythroblasts express both IRP-repressible ALAS2 and non-IRP-repressible ferroportin 1b. The unique combination of IRP targets likely accounts for the tissue-specific phenotype of human GLRX5 deficiency. PMID- 20364085 TI - Proteasomal degradation of retinoid X receptor alpha reprograms transcriptional activity of PPARgamma in obese mice and humans. AB - Obese patients have chronic, low-grade inflammation that predisposes to type 2 diabetes and results, in part, from dysregulated visceral white adipose tissue (WAT) functions. The specific signaling pathways underlying WAT dysregulation, however, remain unclear. Here we report that the PPARgamma signaling pathway operates differently in the visceral WAT of lean and obese mice. PPARgamma in visceral, but not subcutaneous, WAT from obese mice displayed increased sensitivity to activation by its agonist rosiglitazone. This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice. Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT. Finally, PPARgamma-RXRbeta heterodimers, but not PPARgamma-RXRalpha complexes, were able to efficiently dismiss the transcriptional corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) upon agonist binding. Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation. Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans. PMID- 20364086 TI - Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes. AB - Potassium (K+) channels in the inner mitochondrial membrane influence cell function and survival. Increasing evidence indicates that multiple signaling pathways and pharmacological actions converge on mitochondrial ATP-sensitive K+ (mitoKATP) channels and PKC to confer cytoprotection against necrotic and apoptotic cell injury. However, the molecular structure of mitoKATP channels remains unresolved, and the mitochondrial phosphoprotein(s) that mediate cytoprotection by PKC remain to be determined. As mice deficient in the main sarcolemmal gap junction protein connexin 43 (Cx43) lack this cytoprotection, we set out to investigate a possible link among mitochondrial Cx43, mitoKATP channel function, and PKC activation. By patch-clamping the inner membrane of subsarcolemmal murine cardiac mitochondria, we found that genetic Cx43 deficiency, pharmacological connexin inhibition by carbenoxolone, and Cx43 blockade by the mimetic peptide 43GAP27 each substantially reduced diazoxide mediated stimulation of mitoKATP channels. Suppression of mitochondrial Cx43 inhibited mitoKATP channel activation by PKC. MitoKATP channels of interfibrillar mitochondria, which do not contain any detectable Cx43, were insensitive to both PKC activation and diazoxide, further demonstrating the role of Cx43 in mitoKATP channel stimulation and the compartmentation of mitochondria in cell signaling. Our results define a role for mitochondrial Cx43 in protecting cardiac cells from death and provide a link between cytoprotective stimuli and mitoKATP channel opening, making Cx43 an attractive therapeutic target for protection against cell injury. PMID- 20364087 TI - IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. AB - Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in gammadelta but not alphabeta T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vgamma5+ gammadelta T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL 17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of gammadelta T cell deficient mice. Importantly, gammadelta T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal gammadelta T cells in innate immunity against S. aureus cutaneous infection. PMID- 20364088 TI - Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival. AB - At least 10 enteroendocrine cell types have been identified, and the peptide hormones they secrete have diverse functions that include regulation of glucose homeostasis, food intake, and gastric emptying. Mice lacking individual enteroendocrine hormones, their receptors, or combinations of these have shed light on the role of these hormones in the regulation of energy homeostasis. However, because enteroendocrine hormones have partially overlapping functions, these loss-of-function studies produced only minor phenotypes, and none of the enteroendocrine hormones was shown to be essential for life. To examine the effect of loss of all enteroendocrine cells and hormones on energy homeostasis, we generated mice with intestinal-specific ablation of the proendocrine transcription factor neurogenin 3 (referred to herein as Ngn3Deltaint mice). Ngn3Deltaint mice were deficient for all enteroendocrine cells and hormones, and died with a high frequency during the first week of life. Mutant mice were growth retarded and had yellowish stool suggestive of steatorrhea. Subsequent analyses revealed that Ngn3Deltaint mice had impaired lipid absorption, reduced weight gain, and improved glucose homeostasis. Furthermore, intestinal epithelium of the mutant mice showed an enlarged proliferative crypt compartment and accelerated cell turnover but no changes to goblet and Paneth cell numbers. Enterocytes had shorter microvilli, but the expression of the main brush border enzymes was unaffected. Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium. PMID- 20364089 TI - Control of vaccinia virus skin lesions by long-term-maintained IFN-gamma+TNF alpha+ effector/memory CD4+ lymphocytes in humans. AB - Vaccinia virus (VV) vaccination is used to immunize against smallpox and historically was considered to have been successful if a skin lesion formed at the vaccination site. While antibody responses have been widely proposed as a correlate of efficacy and protection in humans, the role of cellular and humoral immunity in VV-associated skin lesion formation was unknown. We therefore investigated whether long-term residual humoral and cellular immune memory to VV, persisting 30 years after vaccination, could control VV-induced skin lesion in revaccinated individuals. Here, we have shown that residual VV-specific IFN gamma+TNF-alpha+ or IFN-gamma+IL-2+ CD4+ lymphocytes but not CD8+ effector/memory lymphocytes expressing a skin-homing marker are inversely associated with the size of the skin lesion formed in response to revaccination. Indeed, high numbers of residual effector T cells were associated with lower VV skin lesion size after revaccination. In contrast, long-term residual VV-specific neutralizing antibody (NAbs) titers did not affect skin lesion formation. However, the size of the skin lesion strongly correlated with high levels of NAbs boosted after revaccination. These findings demonstrate a potential role for VV-specific CD4+ responses at the site of VV-associated skin lesion, thereby providing new insight into immune responses at these sites and potentially contributing to the development of new approaches to measure the efficacy of VV vaccination. PMID- 20364090 TI - Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice. AB - Clinical trials of oncolytic virotherapy have shown low toxicity and encouraging signs of efficacy. However, it remains critically important to develop methods for systemic viral delivery if such therapies are to be clinically implemented to treat established tumors. In this respect, much effort is being focused on combining oncolytic viruses with standard treatment modalities such as inhibitors of VEGF165 (an alternatively spliced isoform of VEGF-A) signaling, which are widely used to treat several different cancers. Here, we have demonstrated that combining VEGF165 inhibitors with systemic delivery of oncolytic viruses leads to substantial regression and cure of established tumors in immunocompetent mice. We have shown that manipulating VEGF165-mediated signaling by administering VEGF165 to mice harboring mouse melanoma cells that do not express VEGF165 and by administering a VEGF inhibitor and then withdrawing treatment to allow VEGF levels to rebound in mice harboring mouse melanoma cells expressing VEGF165 allows tumor-associated endothelial cells transiently to support viral replication. This approach led to direct tumor cell lysis and triggered innate immune-mediated attack on the tumor vasculature. It also resulted in long-term antitumor effects, even against tumors in which viral replication is poorly supported. Since this combinatorial approach targets the tumor endothelium, we believe these data have direct, wide-ranging, and immediate clinical applicability across a broad range of tumor types. PMID- 20364092 TI - How we are born. AB - Human reproduction is relatively inefficient. Nearly 30% of pregnancies result in spontaneous losses, which are both a clinical problem and a psychological stress to the families involved. Furthermore, although the human population is growing rapidly and is predicted to reach 9 billion by 2050, 15% of couples worldwide are childless because of infertility. Many underlying causes of infertility have been overcome by assisted reproductive technologies such as in vitro fertilization, yet pregnancy success rates using such approaches remain disappointingly low. Since mechanistic approaches to study human reproductive processes are ethically restricted, future advances in fertility treatment and the development of new contraceptives rely predominantly on the study of the factors influencing reproduction in model systems. The articles in this Reproductive Biology Review series present updates on the current understanding of various reproductive processes in model systems and raise questions that need to be addressed if we are to improve human reproductive health. PMID- 20364091 TI - KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. AB - The linkage of Kaposi sarcoma (KS) to infection by a novel human herpesvirus (Kaposi sarcoma-associated herpesvirus [KSHV]) is one of the great successes of contemporary biomedical research and was achieved by using advanced genomic technologies in a manner informed by a nuanced understanding of epidemiology and clinical investigation. Ongoing efforts to understand the molecular mechanisms by which KSHV infection predisposes to KS continue to be powerfully influenced by insights emanating from the clinic. Here, recent developments in KS pathogenesis are reviewed, with particular emphasis on clinical, pathologic, and molecular observations that highlight the many differences between this process and tumorigenesis by other oncogenic viruses. PMID- 20364093 TI - The key role of vitamin A in spermatogenesis. AB - Spermatogenesis in adult mammals is highly organized, with the goal being continual sperm production. Vertebrate testes are arranged into recurring cellular associations that vary with time and distance along the tubule. These changes over time and distance are designated the cycle of the seminiferous epithelium and the spermatogenic wave, respectively. In this Review, we briefly outline the roles that follicle-stimulating hormone (FSH) and testosterone play in regulating spermatogenesis and describe our current understanding of how vitamin A regulates germ cell differentiation and how it may lead to the generation of both the cycle of the seminiferous epithelium and the spermatogenic wave. PMID- 20364094 TI - The ovary: basic biology and clinical implications. AB - The classical view of ovarian follicle development is that it is regulated by the hypothalamic-pituitary-ovarian axis, in which gonadotropin-releasing hormone (GnRH) controls the release of the gonadotropic hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and that ovarian steroids exert both negative and positive regulatory effects on GnRH secretion. More recent studies in mice and humans indicate that many other intra-ovarian signaling cascades affect follicular development and gonadotropin action in a stage- and context specific manner. As we discuss here, mutant mouse models and clinical evidence indicate that some of the most powerful intra-ovarian regulators of follicular development include the TGF-beta/SMAD, WNT/FZD/beta-catenin, and RAS/ERK1/2 signaling pathways and the FOXO/FOXL2 transcription factors. PMID- 20364095 TI - Portrait of an oocyte: our obscure origin. AB - Oocytes play a pivotal role in the cycle of human life. As we discuss here, after emerging from germline stem cells in the fetus, they grow in a follicular niche in which development is harmonized for timely ovulation and hormone secretion after puberty. Most human oocytes have poor developmental competence and are peculiarly vulnerable to chromosomal malsegregation, especially as women pass the optimal years of fertility and may begin to turn to assisted reproductive technologies (ARTs) and egg donation. Research needs to focus on the molecular factors involved and the environmental niche required for optimal development of oocytes, with the aim of increasing their numbers and quality for ARTs, since these are the factors that so often limit human fertility. PMID- 20364096 TI - Fertilization: a sperm's journey to and interaction with the oocyte. AB - Mammalian fertilization comprises sperm migration through the female reproductive tract, biochemical and morphological changes to sperm, and sperm-egg interaction in the oviduct. Recent gene knockout approaches in mice have revealed that many factors previously considered important for fertilization are largely dispensable, or if they are essential, they have an unexpected function. These results indicate that what has been observed in in vitro fertilization (IVF) differs significantly from what occurs during "physiological" fertilization. This Review focuses on the advantages of studying fertilization using gene-manipulated animals and highlights an emerging molecular mechanism of mammalian fertilization. PMID- 20364097 TI - Making the blastocyst: lessons from the mouse. AB - Mammalian preimplantation development, which is the period extending from fertilization to implantation, results in the formation of a blastocyst with three distinct cell lineages. Only one of these lineages, the epiblast, contributes to the embryo itself, while the other two lineages, the trophectoderm and the primitive endoderm, become extra-embryonic tissues. Significant gains have been made in our understanding of the major events of mouse preimplantation development, and recent discoveries have shed new light on the establishment of the three blastocyst lineages. What is less clear, however, is how closely human preimplantation development mimics that in the mouse. A greater understanding of the similarities and differences between mouse and human preimplantation development has implications for improving assisted reproductive technologies and for deriving human embryonic stem cells. PMID- 20364100 TI - Comparative analysis of DNA methylation in transgenic mice with unstable CGG repeats from FMR1 gene. AB - Methylation of CpG sequences in and around CGG triplet repeats in FMR1 gene has strong correlation with manifestation of the fragile X syndrome in human patients. In contrast, we have observed a lack of correlation between repeat instability and DNA methylation in three different transgenic mouse models harboring unstable CGG repeats. Further we have demonstrated that the endogenous copy of mouse Fmr1 gene remains unmethylated both in males and females. These results imply that methylation and repeat instability are independent events and raise the possibility that methylation could also result in repression of FMR1 transcription in the absence of repeat expansion. PMID- 20364098 TI - Uterine disorders and pregnancy complications: insights from mouse models. AB - Much of our knowledge of human uterine physiology and pathology has been extrapolated from the study of diverse animal models, as there is no ideal system for studying human uterine biology in vitro. Although it remains debatable whether mouse models are the most suitable system for investigating human uterine function(s), gene-manipulated mice are considered by many the most useful tool for mechanistic analysis, and numerous studies have identified many similarities in female reproduction between the two species. This Review brings together information from studies using animal models, in particular mouse models, that shed light on normal and pathologic aspects of uterine biology and pregnancy complications. PMID- 20364099 TI - The placenta: transcriptional, epigenetic, and physiological integration during development. AB - The placenta provides critical transport functions between the maternal and fetal circulations during intrauterine development. Formation of this interface relies on coordinated interactions among transcriptional, epigenetic, and environmental factors. Here we describe these mechanisms in the context of the differentiation of placental cells (trophoblasts) and synthesize current knowledge about how they interact to generate a functional placenta. Developing an understanding of these pathways contributes to an improvement of our models for studying trophoblast biology and sheds light on the etiology of pregnancy complications and the in utero programming of adult diseases. PMID- 20364102 TI - Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells. AB - Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles. The mitochondrial permeability transition (MPT) results in mitochondrial depolarization and increased reactive oxygen species production, which can trigger autophagy. Therefore, we hypothesized that the MPT may have a role in signaling autophagy in cardiac cells. Mitochondrial membrane potential was lower in HL-1 cells subjected to starvation compared to cells maintained in full medium. Mitochondrial membrane potential was preserved in starved cells treated with cyclosporin A (CsA), suggesting the MPT pore is associated with starvation-induced depolarization. Starvation-induced autophagy in HL-1 cells, neonatal rat cardiomyocytes and adult mouse cardiomyocytes was inhibited by CsA. Starvation failed to induce autophagy in CypD-deficient murine cardiomyocytes, whereas in myocytes from mice overexpressing CypD the levels of autophagy were enhanced even under fed conditions. Collectively, these results demonstrate a role for CypD and the MPT in the initiation of autophagy. We also analyzed the role of the MPT in the degradation of mitochondria by biochemical analysis and electron microscopy. HL-1 cells subjected to starvation in the presence of CsA had higher levels of mitochondrial proteins (by Western blot), more mitochondria and less autophagosomes (by electron microscopy) than cells starved in the absence of CsA. Our results suggest a physiologic function for CypD and the MPT in the regulation of starvation-induced autophagy. Starvation-induced autophagy regulated by CypD and the MPT may represent a homeostatic mechanism for cellular and mitochondrial quality control. PMID- 20364103 TI - DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis. AB - Chromosome pairing and synapsis during meiotic prophase requires the formation and repair of DNA double-strand breaks (DSBs) by the topoisomerase-like enzyme SPO11. Chromosomes, or chromosomal regions, that lack a pairing partner, such as the largely heterologous X and Y chromosomes, show delayed meiotic DSB repair and are transcriptionally silenced. Herein, we review meiosis-specific aspects of DSB repair in relation to homology recognition and meiotic silencing of heterologous regions. We propose a dynamic interplay between progression of synapsis and persistent meiotic DSBs. Signaling from these persistent breaks could inhibit heterologous synapsis and stimulate meiotic silencing of the X and Y chromosomes. PMID- 20364104 TI - Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo. AB - There is growing evidence that the Rho/Rho-kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and proliferation. The aim of this study was to explore the anti-tumor effects of Rho/ROCK inhibitor, fasudil, including the possible mechanisms involved in the suppression of the glioblastoma (GBM) cell line progression in vitro and in vivo. After T98G and U251 cells were treated with various concentrations of fasudil, Y27632, and ROCK siRNA, the effects of ROCK inhibitors on migration, invasion, invasion related gene expressions, proliferation and apoptosis of cultured tumor cells were examined. The results indicated that fasudil significantly inhibited not only proliferation, migration and invasiveness (p < 0.05) but also the mRNA and protein expressions of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Moreover, fasudil treatment resulted in a dose-dependent increase of apoptosis in T98G and U251. The intracranial xenograft models were established. The cryosection of the tumor and the survival time of mice in each group indicated that fasudil could inhibit glioma invasion and growth in vivo. Based on the results, fasudil suppresses the progression of GBM in vitro and in vivo by inhibiting ROCK. This could be linked to the decreased MMP-2 expression and the induction of apoptosis in tumor cells. The Rho/ROCK signaling pathway may prove to be a promising target in anti-tumor therapy. Fasudil may be an attractive anti tumor drug candidate for the treatment of GBM. PMID- 20364105 TI - Quantitative assessment of AKAP12 promoter methylation in colorectal cancer using methylation-sensitive high resolution melting: Correlation with Duke's stage. AB - BACKGROUND: The expression of AKAP12 (A Kinase anchoring protein 12) is markedly reduced in a variety of cancers. The purpose of this study was to establish a methylation-sensitive high resolution melting (MS-HRM) assay for the quantitative detection of AKAP12 promoter methylation and expression and the association with clinicopathological variables in human colorectal cancer. We also assessed the effect of AKAP12 re-expression on cell growth and colony formation. RESULTS: Downregulation or loss of AKAP12 mRNA expression was detected in 31 of 45 tissue samples (68.9%). No significant correlation was observed between the reduced expression levels and patient age, gender, Duke's stage or tumor differentiation. Methylation (>1%) of the AKAP12 promoter region was present in 35 of 45 (77.8%) carcinoma tissue samples and 6 of 45 (13.3%) adjacent tissue samples. AKAP12 methylation was significantly higher in the colorectal cancer tissues exhibiting advanced Duke's stages. Treatment of the three colorectal carcinoma cell lines (LoVo, COLO320 and SW480) with completely methylated AKAP12 with inhibitors of DNA methyltransferase (5-Aza-2'-deoxycytidine) markedly increased expression of AKAP12 and decreased methylation levels. Ectopic expression of AKAP12 in the LoVo cell line suppressed cell growth and inhibited colony formation. METHODS: The AKAP12 gene was examined by quantitative RT-PCR, MS-HRM analysis and bisulfite sequencing in 45 paired tissue samples obtained from primary colorectal carcinomas and the corresponding adjacent tissues. In addition, five colorectal carcinoma cell lines (LoVo, COLO205, SW480, LS174T and COLO320) were investigated and western blot analysis was used to investigate changes in protein expression. A proliferation assay and soft agar assay were performed after overexpression of AKAP12. CONCLUSION: Our study demonstrated that MS-HRM is a robust, fast and sensitive method for AKAP12 methylation analysis. AKAP12 methylation represents a potential molecular biomarker for predicting the malignancy of this cancer. PMID- 20364106 TI - Therapeutic safety and effects of adjuvant autologous RetroNectin activated killer cell immunotherapy for patients with primary hepatocellular carcinoma after radiofrequency ablation. AB - Hepatocellular carcinoma (HCC) recurs frequently after minimally invasive therapy. Adoptive immunotherapy is considered helpful in lowering recurrence and metastasis rates of malignant tumors. In this study, we report the combination of radiofrequency ablation (RFA) and autologous RetroNectin activated killer (RAK) cells in the treatment of HCC patients with a tumor size less than 4 cm. Autologous RAK cells were transfused via an intravenous drip into the patients. Flow cytometry was used to assess the change of percentages of lymphocyte subsets in the peripheral blood of the patients. Computed tomography was used to observe the tumor recurrent conditions of patients by every 2 m. During a seven-month follow-up, no severe adverse events, recurrences or deaths were observed in all 7 HCC patients. These preliminary results suggest the feasability and safety of the combined therapeutic regimen for HCC, and that the RAK cell adoptive immunotherapy might be helpful in preventing recurrence in HCC patients after RFA. PMID- 20364107 TI - Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells. AB - BACKGROUND: Aquaporins (AQPs) are expressed in many different tumor cell types in human. New evidence for the involvement of AQPs in cell migration and proliferation adds AQPs to an expanding list of effectors in tumor biology. AIMS: The aim of this study was to investigate whether AQP3 expression in the human gastric carcinoma cell lines, AGS and SGC7901, enhances cell migration and proliferation. RESULTS: Here, we showed that AQP3 is expressed in the human gastric cancer cell lines, AGS and SGC7901. The hEGF induced AQP3 expression in a time- and dose-dependent manner and increased gastric cancer cell migration and proliferation. AQP3 knockdown by siRNA inhibited hEGF-induced AQP3 expression and thus cell migration and proliferation. Furthermore, a mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126 inhibited hEGF-induced AQP3 expression and cell migration or proliferation. METHODS: Cultured AGS or SGC7901 cells were treated with human epidermal growth factor (hEGF) and subjected to cell migration assay and cell proliferation assay. The expression or activation level of proteins was analyzed by western blot. AQP3 knockdown was obtained by small interfering (si)RNA. CONCLUSIONS: Collectively, our findings provide for the first time that AQP3 plays a critical role in hEGF induced cancer cell migration and proliferation and that hEGF induces AQP3 expression via ERK signal transduction pathways. These finds provide evidence for a novel role of AQP3 in human gastric carcinoma as a potentially important determinant of tumor growth and spread. PMID- 20364108 TI - Reconciling the positive and negative roles of histone H2A.Z in gene transcription. AB - The incorporation of variant histone H2A.Z within chromatin is important for proper gene expression and genome stability. H2A.Z is inserted at discrete loci by the Swr1 or Swr1-like remodeling complexes, although very little is known about the nature of the targeting mechanism involved. Replacement of canonical histone H2A for H2A.Z has been shown to modify nucleosome dynamics, although discrepancies still exist in the literature regarding the mechanisms. Recent experiments have shown that H2A.Z can allow nucleosomes to adopt stable translational positions as compared to H2A, which could influence the accessibility to DNA regulatory proteins. This review provides a brief overview of H2A.Z biology and presents hypotheses that could reconcile contradictory reports that are found in the literature regarding the influence of H2A.Z on nucleosome stability. PMID- 20364109 TI - FYCO1: linking autophagosomes to microtubule plus end-directing molecular motors. AB - In mammalian cells, autophagosomes are transported along microtubule tracks to fuse with late endosomes or lysosomes. Autophagosomal membranes harbor the lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) and phosphatidylethanolamine conjugated ATG8/LC3/GABARAP family proteins. The small GTPase Rab7 is implicated in autophagosomal transport and fusion. We have recently reported that a previously uncharacterized protein FYVE and coiled-coil domain-containing 1 (FYCO1) functions as an adapter linking autophagosomes to microtubule plus end directed molecular motors. FYCO1 binds to both LC3, PtdIns(3)P and Rab7, and contains a domain responsible for microtubule plus end-dependent transport. When cells are depleted for FYCO1, autophagosomes accumulate in perinuclear clusters, whereas overexpression of FYCO1 redistributes Rab7-positive vesicles to microtubule plus ends at the cell periphery. FYCO1 is likely selectively recruited to autophagosomal membranes via a mechanism involving a conformational change upon LC3-LIR interaction to expose the FYVE domain for PtdIns(3)P binding. PMID- 20364110 TI - PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three dimensional environments. PMID- 20364111 TI - A genomic screen for yeast mutants defective in mitophagy. AB - Mitochondria autophagy (mitophagy) is the process of selective degradation of mitochondria that has an important role in mitochondrial quality control. To gain insight into the molecular mechanism of mitophagy, we screened a yeast knockout library for strains that are defective in mitophagy. We found 32 strains that showed a complete or partial block of mitophagy. One of the genes identified, YLR356W, is required for mitophagy, but not for macroautophagy or other types of selective autophagy. The deletion of YLR356W partially inhibits mitophagy during starvation, whereas there is almost complete inhibition at post-log phase. Accordingly, we hypothesize that Ylr356w is required to detect or present aged or dysfunctional mitochondria when cells reach the post-log phase. PMID- 20364112 TI - Prostate cancer in African-American men and polymorphism in the calcium-sensing receptor. AB - BACKGROUND: Prospective epidemiologic studies indicate that the risk for advanced prostate cancer is increased among men with high levels of serum calcium. Because serum calcium levels are influenced by the calcium-sensing receptor (CaSR), we examined prostate cancer in African-American men in relation to three single nucleotide polymorphisms (SNPs) in the CaSR gene, A986S, R990G and Q1011E. This is the first study of CaSR polymorphisms and risk of prostate cancer. RESULTS: The CaSR genotypes were not associated with prostate cancer overall. However, we observed significant heterogeneity by disease stage for the Q1011E polymorphism (p = 0.02). Advanced cases were significantly less likely than controls or localized cases to be homozygous for the minor allele of the Q1011E polymorphism (1 vs. 5%). Cases with advanced disease were six times less likely to carry two copies of the minor allele than were controls (OR = 0.16, p = 0.02) or localized cases (OR = 0.15, p = 0.01) and were significantly older at diagnosis (68.8 +/- 5.7 vs. 64.0 +/- 9.0 y for the QQ and EE genotypes, p = 0.004). METHODS: We genotyped three CaSR SNPs for 458 African-American prostate cancer cases and 248 controls from a population-based case-control study, the California Collaborative Prostate Cancer Study. CONCLUSIONS: The CaSR Q1011E minor allele, which is common in populations with African ancestry, may be associated with a less aggressive form of prostate cancer among African-American men. PMID- 20364113 TI - Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells. AB - mTOR is a major biological switch, coordinating an adequate response to changes in energy uptake (amino acids, glucose), growth signals (hormones, growth factors) and environmental stress. mTOR kinase is highly conserved through evolution from yeast to man and in both cases, controls autophagy and cellular translation in response to nutrient stress. mTOR kinase is the catalytic component of two distinct multiprotein complexes called mTORC1 and mTORC2. In addition to mTOR, mTORC1 contains Raptor, mLST8 and PRAS40. mTORC2 contains mTOR, Rictor, mSIN1 and Protor-1. mTORC1 activates p70S6K, which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation. mTORC2 activates AKT directly by phosphorylating Serine 473. pAKT(S473) phosphorylates TSC2 (tuberin) and inactivates it, preventing its association with TSC1 (hamartin) and the inhibition of Rheb, an activator of mTOR. pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state. PMID- 20364114 TI - MicroRNA-602 regulating tumor suppressive gene RASSF1A is overexpressed in hepatitis B virus-infected liver and hepatocellular carcinoma. AB - AIMS: It is important to understand the role of microRNA in the transformation from chronic HBV hepatitis to hepatocellular carcinoma in hepatocarcinogenesis. Relationship of microRNA-602 with chronic HBV hepatitis, liver cirrhosis and HCC was investigated in this article. RESULTS: (1) 14 MicroRNAs were aberrantly expressed in HCC and CL compared with NL. Among these, microRNA-602 expression in CH, LC, NT and HCC was 2.939, 3.234, 2.439 and 4.134 times of that in NL respectively, which was significantly different (p < 0.01 for all vs. NL); RASSF1A expression in LC and HCC was lower than that in NL, while P73 protein expression in CL was higher than that in NL and HCC. (2) MicroRNA-602 expression in HepG2 2.2.15 and HepG2-HBX was 2.643 and 3.48 times of that in HepG2 (p < 0.05 for both). (3) MicroRNA-602 inhibition in HepG2 cells was associated with RASSF1A mRNA and protein expression increased to 4.37, 3.01 times respectively of those not, with cell apoptosis increased and cell proliferation rate decreased significantly, changes were similar in HepG2-HBX cells. METHODS: (1) MicroRNA expression was investigated in normal (NL), chronic HBV hepatitis (CH), HBV positive cirrhotic (CL), HBV-positive HCC and corresponding normal para-tumorous livers (NT) and hepatoma cells was evaluated with microRNA microarray and verified by real-time PCR, and microRNA-602 was selected for further study. Expression of miR602-target genes RASSF1A and P73 were detected with RT-PCR and western blot. (2) MicroRNA-602 expression in HepG2 and HepG2-HBX was inhibited by miR-602 inhibitor transfection; RASSF1A and P73 expression was detected and cell apoptosis and proliferation were detected. CONCLUSIONS: MicroRNA-602 plays a pro carcinogenic role in HBV-related hepatocarcinogenesis by inhibiting RASSF1A. MicroRNA-602 might be an early diagnostic marker for HBV-mediated HCC. PMID- 20364115 TI - DNA methylation in adult stem cells: new insights into self-renewal. AB - Methylation of cytosine residues in the context of CpG dinucleotides within mammalian DNA is an epigenetic modification with profound effects on transcriptional regulation. A group of enzymes, the DNA methyltransferases (DNMTs) tightly regulate both the initiation and maintenance of these methyl marks. Loss of critical components of this enzymatic machinery results in growth, viability, and differentiation defects in both mice and humans, supporting the notion that this epigenetic modification is essential for proper development. Beyond this, DNA methylation also provides a potent epigenetic mechanism for cellular memory needed to silence repetitive elements and preserve lineage specificity over repeated cell divisions throughout adulthood. Recent work highlighting the specialized roles of DNA methylation and methyltransferases in maintaining adult somatic stem cell function suggests that further dissection of these mechanisms will shed new light on the complex nature of self-renewal. PMID- 20364116 TI - 2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells. AB - Malignant cells have a demonstrably greater sensitivity to glucose deprivation induced cytotoxicity than normal cells. This has been hypothesized to be due to a higher level of reactive oxygen species (ROS) production in cancer cells leading to the increased need for reducing equivalents, produced by glucose metabolism, to detoxify hydroperoxides. Because complete glucose deprivation cannot be achieved in vivo, it has been proposed that agents that antagonize glucose metabolism, such as 2-deoxy-D-glucose (2DG), can mimic in vitro glucose deprivation that selectively kills cancer cells by oxidative stress. To test this hypothesis, neuroblastoma cell lines were treated with 2DG and the effects on clonogenic survival and the distribution of cellular phenotypes among surviving colonies was determined. The results showed that all three major cell types found in neuroblastoma (Schwann, Neuronal and Intermediate) were sensitive to 2DG induced clonogenic cell killing. Furthermore, treatment with the thiol antioxidant, N-acetyl cysteine or with polyethylene glycol-conjugated superoxide dismutase and catalase, protected neuroblastoma cells from 2DG-induced cell killing. Finally normal non-immortalized neural precursor cells were relatively resistant to 2DG-induced cell killing when compared to neuroblastoma cell lines. These results support the hypothesis that inhibitors of glucose metabolism could represent useful adjuvants in the treatment of neuroblastoma by selectively enhancing metabolic oxidative stress. PMID- 20364117 TI - Growth suppression of cervical carcinoma by pigment epithelium-derived factor via anti-angiogenesis. AB - Pigment epithelium-derived factor (PEDF), an angiogenesis inhibitor with multiple other functions, balances angiogenesis in the eye and blocks tumor progression. Cervical cancer, an angiogenesis-dependent tumor, is the second most common cancer in women without effective treatment. It has been reported that PEDF can inhibit several types of tumors, however, the potential of PEDF for the treatment of cervical carcinoma has not been well explored. The present study was designed to investigate the effect of recombinant PEDF on the neovascularization and growth of cervical carcinoma. We found for the first time that PEDF was downregulated apparently in human cervical carcinoma nests compared to either normal cervical epithelium or nonneoplastic peritumoral epithelium, suggesting potential anti-angiogenesis function by supplement of PEDF in cervical carcinoma. Intraperitoneal injection of PEDF in xenografted cervical carcinoma mice suppressed tumor growth with 68% reduction. Microvessel density in tumor tissues treated with PEDF was significantly decreased. PEDF dose-dependently inhibited proliferation and induced apoptosis of endothelial cells, but had no direct effect on proliferation and apoptosis of Hela cells under both normoxia and hypoxia. These results suggested that PEDF suppressed tumor growth by blocking angiogenesis instead of a direct cytotoxic effect on tumor cells. VEGF, a major angiogenic stimulator, was downregulated by PEDF in Hela cells by downregulation of HIF-1alpha, a crucial transcriptional factor for VEGF expression. Downregulation of VEGF expression in tumor cells through inhibiting HIF-1alpha, thus attenuating the paracrine effect of VEGF on endothelial cells, may represent a mechanism for the anti-angiogenic activity of PEDF. PMID- 20364118 TI - hRad21 overexpresses and localizes to the ALT-associated promyelocytic leukemia body in ALT cells. AB - Telomerase-negative immortalized cells maintain their telomeres through a telomerase-independent pathway termed alternative lengthening of telomeres (ALT). The mechanism of ALT is based on homologous recombination (HR). A hallmark of ALT cells is presence of a nuclear structure termed ALT-associated promyelocytic leukemia body (APB). Here, we demonstrated that hRAD21, an important subunit of cohesin complex, was overexpressed in ALT cells. We additionally showed that hRAD21 protein localized to APB in ALT cells. Thus, one role of hRAD21 appeared to involve telomere maintenance in ALT cells. We suggested that hRAD21 facilitated telomere HR in ALT cells by participating in APB formation. PMID- 20364119 TI - Single-unit in vivo recordings from the optic chiasm of rat. AB - Information about the visual world is transmitted to the brain in sequences of action potentials in retinal ganglion cell axons that make up the optic nerve. In vivo recordings of ganglion cell spike trains in several animal models have revealed much of what is known about how the early visual system processes and encodes visual information. However, such recordings have been rare in one of the most common animal models, the rat, possibly owing to difficulty in detecting spikes fired by small diameter axons. The many retinal disease models involving rats motivate a need for characterizing the functional properties of ganglion cells without disturbing the eye, as with intraocular or in vitro recordings. Here, we demonstrate a method for recording ganglion cell spike trains from the optic chiasm of the anesthetized rat. We first show how to fabricate tungsten-in glass electrodes that can pick up electrical activity from single ganglion cell axons in rat. The electrodes outperform all commercial ones that we have tried. We then illustrate our custom-designed stereotaxic system for in vivo visual neurophysiology experiments and our procedures for animal preparation and reliable and stable electrode placement in the optic chiasm. PMID- 20364120 TI - Recognition of a signal peptide by the signal recognition particle. AB - Targeting of proteins to appropriate subcellular compartments is a crucial process in all living cells. Secretory and membrane proteins usually contain an amino-terminal signal peptide, which is recognized by the signal recognition particle (SRP) when nascent polypeptide chains emerge from the ribosome. The SRP ribosome nascent chain complex is then targeted through its GTP-dependent interaction with SRP receptor to the protein-conducting channel on endoplasmic reticulum membrane in eukaryotes or plasma membrane in bacteria. A universally conserved component of SRP (refs 1, 2), SRP54 or its bacterial homologue, fifty four homologue (Ffh), binds the signal peptides, which have a highly divergent sequence divisible into a positively charged n-region, an h-region commonly containing 8-20 hydrophobic residues and a polar c-region. No structure has been reported that exemplifies SRP54 binding of any signal sequence. Here we have produced a fusion protein between Sulfolobus solfataricus SRP54 (Ffh) and a signal peptide connected via a flexible linker. This fusion protein oligomerizes in solution through interaction between the SRP54 and signal peptide moieties belonging to different chains, and it is functional, as demonstrated by its ability to bind SRP RNA and SRP receptor FtsY. We present the crystal structure at 3.5 A resolution of an SRP54-signal peptide complex in the dimer, which reveals how a signal sequence is recognized by SRP54. PMID- 20364121 TI - Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. AB - Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration. PMID- 20364122 TI - MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. AB - Within the circulatory system, blood flow regulates vascular remodelling, stimulates blood stem cell formation, and has a role in the pathology of vascular disease. During vertebrate embryogenesis, vascular patterning is initially guided by conserved genetic pathways that act before circulation. Subsequently, endothelial cells must incorporate the mechanosensory stimulus of blood flow with these early signals to shape the embryonic vascular system. However, few details are known about how these signals are integrated during development. To investigate this process, we focused on the aortic arch (AA) blood vessels, which are known to remodel in response to blood flow. By using two-photon imaging of live zebrafish embryos, we observe that flow is essential for angiogenesis during AA development. We further find that angiogenic sprouting of AA vessels requires a flow-induced genetic pathway in which the mechano-sensitive zinc finger transcription factor klf2a induces expression of an endothelial-specific microRNA, mir-126, to activate Vegf signalling. Taken together, our work describes a novel genetic mechanism in which a microRNA facilitates integration of a physiological stimulus with growth factor signalling in endothelial cells to guide angiogenesis. PMID- 20364123 TI - The molecular basis for water taste in Drosophila. AB - The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis. Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources, but little is known about the underlying molecular mechanism for water taste detection. Here we identify a member of the degenerin/epithelial sodium channel family, PPK28, as an osmosensitive ion channel that mediates the cellular and behavioural response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons, and that loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypo-osmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behaviour, providing the framework for examining the molecular basis for water detection in other animals. PMID- 20364124 TI - Isolation of the elusive supercomplex that drives cyclic electron flow in photosynthesis. AB - Photosynthetic light reactions establish electron flow in the chloroplast's thylakoid membranes, leading to the production of the ATP and NADPH that participate in carbon fixation. Two modes of electron flow exist-linear electron flow (LEF) from water to NADP(+) via photosystem (PS) II and PSI in series and cyclic electron flow (CEF) around PSI (ref. 2). Although CEF is essential for satisfying the varying demand for ATP, the exact molecule(s) and operational site are as yet unclear. In the green alga Chlamydomonas reinhardtii, the electron flow shifts from LEF to CEF on preferential excitation of PSII (ref. 3), which is brought about by an energy balancing mechanism between PSII and PSI (state transitions). Here, we isolated a protein supercomplex composed of PSI with its own light-harvesting complex (LHCI), the PSII light-harvesting complex (LHCII), the cytochrome b(6)f complex (Cyt bf), ferredoxin (Fd)-NADPH oxidoreductase (FNR), and the integral membrane protein PGRL1 (ref. 5) from C. reinhardtii cells under PSII-favouring conditions. Spectroscopic analyses indicated that on illumination, reducing equivalents from downstream of PSI were transferred to Cyt bf, whereas oxidised PSI was re-reduced by reducing equivalents from Cyt bf, indicating that this supercomplex is engaged in CEF (Supplementary Fig. 1). Thus, formation and dissociation of the PSI-LHCI-LHCII-FNR-Cyt bf-PGRL1 supercomplex not only controlled the energy balance of the two photosystems, but also switched the mode of photosynthetic electron flow. PMID- 20364125 TI - Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. AB - Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by vascular malformations. Many affected individuals develop recurrent nosebleeds, which can severely affect their quality of life and are clinically difficult to treat. We report here that treatment with thalidomide reduced the severity and frequency of nosebleeds (epistaxis) in the majority of a small group of subjects with HHT tested. The blood hemoglobin levels of the treated individuals rose as a result of reduced hemorrhage and enhanced blood vessel stabilization. In mice heterozygous for a null mutation in the Eng gene (encoding endoglin), an experimental model of HHT, thalidomide treatment stimulated mural cell coverage and thus rescued vessel wall defects. Thalidomide treatment increased platelet-derived growth factor-B (PDGF-B) expression in endothelial cells and stimulated mural cell activation. The effects of thalidomide treatment were partially reversed by pharmacological or genetic interference with PDGF signaling from endothelial cells to pericytes. Biopsies of nasal epithelium from individuals with HHT treated or not with thalidomide showed that similar mechanisms may explain the effects of thalidomide treatment in humans. Our findings demonstrate the ability of thalidomide to induce vessel maturation, which may be useful as a therapeutic strategy for the treatment of vascular malformations. PMID- 20364126 TI - Activation of membrane-permeant caged PtdIns(3)P induces endosomal fusion in cells. AB - Phosphatidylinositol 3-phosphate (PtdIns(3)P) is a phospholipid residing on early endosomes, where it is proposed to be involved in endosomal fusion. We synthesized membrane-permeant derivatives of PtdIns(3)P, including a caged version that is to our knowledge the first photoactivatable phosphoinositide derivative developed so far. In living cells, photoactivation of caged PtdIns(3)P induced rapid endosomal fusion in an EEA1-dependent fashion, thus providing in vivo evidence that PtdIns(3)P is a sufficient signal for driving this process. PMID- 20364127 TI - Structural and mechanistic basis for a new mode of glycosyltransferase inhibition. AB - Glycosyltransferases are carbohydrate-active enzymes with essential roles in numerous important biological processes. We have developed a new donor analog for galactosyltransferases that locks a representative target enzyme in a catalytically inactive conformation, thus almost completely abolishing sugar transfer. Results with other galactosyltransferases suggest that this unique mode of glycosyltransferase inhibition may also be generally applicable to other members of this important enzyme family. PMID- 20364128 TI - Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP. AB - In the voltage-sensing phosphatase Ci-VSP, a voltage-sensing domain (VSD) controls a lipid phosphatase domain (PD). The mechanism by which the domains are allosterically coupled is not well understood. Using an in vivo assay, we found that the interdomain linker that connects the VSD to the PD is essential for coupling the full-length protein. Biochemical assays showed that the linker is also needed for activity in the isolated PD. We also identified a late step of VSD motion in the full-length protein that depends on the linker. Notably, we found that this VSD motion requires PI(4,5)P2, a substrate of Ci-VSP. These results suggest that the voltage-driven motion of the VSD turns the enzyme on by rearranging the linker into an activated conformation, and that this activated conformation is stabilized by PI(4,5)P2. We propose that Ci-VSP activity is self limited because its decrease of PI(4,5)P2 levels decouples the VSD from the enzyme. PMID- 20364129 TI - Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. AB - Cyclophilin A (CypA) is a ubiquitous cis-trans prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyllysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in Escherichia coli. We determined atomic-resolution structures of acetylated CypA and its complexes with cyclosporine and HIV-1 capsid. Acetylation markedly inhibited CypA catalysis of cis to trans isomerization and stabilized cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonized the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function. PMID- 20364130 TI - Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. AB - p53 binds as a tetramer to DNA targets consisting of two decameric half-sites separated by a variable spacer. Here we present high-resolution crystal structures of complexes between p53 core-domain tetramers and DNA targets consisting of contiguous half-sites. In contrast to previously reported p53-DNA complexes that show standard Watson-Crick base pairs, the newly reported structures show noncanonical Hoogsteen base-pairing geometry at the central A-T doublet of each half-site. Structural and computational analyses show that the Hoogsteen geometry distinctly modulates the B-DNA helix in terms of local shape and electrostatic potential, which, together with the contiguous DNA configuration, results in enhanced protein-DNA and protein-protein interactions compared to noncontiguous half-sites. Our results suggest a mechanism relating spacer length to protein-DNA binding affinity. Our findings also expand the current understanding of protein-DNA recognition and establish the structural and chemical properties of Hoogsteen base pairs as the basis for a novel mode of sequence readout. PMID- 20364131 TI - Single-molecule stepping and structural dynamics of myosin X. AB - Myosin X is an unconventional myosin with puzzling motility properties. We studied the motility of dimerized myosin X using the single-molecule fluorescence techniques polTIRF, FIONA and Parallax to measure the rotation angles and three dimensional position of the molecule during its walk. It was found that Myosin X steps processively in a hand-over-hand manner following a left-handed helical path along both single actin filaments and bundles. Its step size and velocity are smaller on actin bundles than individual filaments, suggesting myosin X often steps onto neighboring filaments in a bundle. The data suggest that a previously postulated single alpha-helical domain mechanically extends the lever arm, which has three IQ motifs, and either the neck-tail hinge or the tail is flexible. These structural features, in conjunction with the membrane- and microtubule binding domains, enable myosin X to perform multiple functions on varied actin structures in cells. PMID- 20364132 TI - Electron diffractive imaging of oxygen atoms in nanocrystals at sub-angstrom resolution. AB - High-resolution imaging of low-atomic-number chemical elements using electron microscopy is challenging and may require the use of high doses of electrons. Electron diffractive imaging, which creates real-space images using diffraction intensities and phase retrieval methods, could overcome such issues, although it is also subject to limitations. Here, we show that a combination of electron diffractive imaging and high-resolution transmission electron microscopy can image individual TiO(2) nanocrystals with a resolution of 70 pm while exposing the specimen to a low dose of electrons. Our approach, which does not require spherical and chromatic aberration correction, can reveal the location of light atoms (oxygen) in the crystal lattice. We find that the unit cell in nanoscale TiO(2) is subtly different to that in the corresponding bulk. PMID- 20364133 TI - Facile synthesis of high-quality graphene nanoribbons. AB - Graphene nanoribbons have attracted attention because of their novel electronic and spin transport properties, and also because nanoribbons less than 10 nm wide have a bandgap that can be used to make field-effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotubes using mechanical sonication in an organic solvent. The nanoribbons are of very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported so far (up to 5e(2)/h and 1,500 cm(2) V(-1) s( 1) for ribbons 10-20 nm in width). Furthermore, at low temperatures, the nanoribbons show phase-coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons is approximately 2% of the starting raw nanotube soot material, significantly higher than previous methods capable of producing high-quality narrow nanoribbons. The relatively high-yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications. PMID- 20364134 TI - Penetration of thin C60 films by metal nanoparticles. AB - Metal nanoparticles supported by thin films are important in the fields of molecular electronics, biotechnology and catalysis, among others. Penetration of these nanoparticles through their supporting films can be undesirable in some circumstances but desirable in others, and is often considered to be a diffusive process. Here, we demonstrate a mechanism for the penetration of thin films and other nanoscopic barriers that is different from simple diffusion. Silver clusters that are soft-landed onto a monolayer of C(60) supported by gold sink through the monolayer in a matter of hours. However, the clusters are stable when landed onto two monolayers of C(60) supported on gold, or on one monolayer of C(60) supported on graphite. With backing from atomistic calculations, these results demonstrate that a metallic substrate exerts attractive forces on metallic nanoparticles that are separated from the substrate by a single monolayer. PMID- 20364135 TI - Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. AB - We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase. However, whether peroxidase intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals. PMID- 20364136 TI - Mutation spectrum revealed by breakpoint sequencing of human germline CNVs. AB - Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 1-30 bp of microhomology, whereas 33% of deletion breakpoints contain 1-367 bp of inserted sequence. The co occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible. PMID- 20364138 TI - Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing. AB - Copy number variants (CNVs) account for the majority of human genomic diversity in terms of base coverage. Here, we have developed and applied a new method to combine high-resolution array comparative genomic hybridization (CGH) data with whole-genome DNA sequencing data to obtain a comprehensive catalog of common CNVs in Asian individuals. The genomes of 30 individuals from three Asian populations (Korean, Chinese and Japanese) were interrogated with an ultra-high-resolution array CGH platform containing 24 million probes. Whole-genome sequencing data from a reference genome (NA10851, with 28.3x coverage) and two Asian genomes (AK1, with 27.8x coverage and AK2, with 32.0x coverage) were used to transform the relative copy number information obtained from array CGH experiments into absolute copy number values. We discovered 5,177 CNVs, of which 3,547 were putative Asian-specific CNVs. These common CNVs in Asian populations will be a useful resource for subsequent genetic studies in these populations, and the new method of calling absolute CNVs will be essential for applying CNV data to personalized medicine. PMID- 20364139 TI - Epitaxial SrTiO3 films with electron mobilities exceeding 30,000 cm2 V(-1) s(-1). AB - The study of quantum phenomena in semiconductors requires epitaxial structures with exceptionally high charge-carrier mobilities. Furthermore, low-temperature mobilities are highly sensitive probes of the quality of epitaxial layers, because they are limited by impurity and defect scattering. Unlike many other complex oxides, electron-doped SrTiO(3) single crystals show high (approximately 10(4) cm(2) V(-1) s(-1)) electron mobilities at low temperatures. High-mobility, epitaxial heterostructures with SrTiO(3) have recently attracted attention for thermoelectric applications, field-induced superconductivity and two-dimensional (2D) interface conductivity. Epitaxial SrTiO(3) thin films are often deposited by energetic techniques, such as pulsed laser deposition. Electron mobilities in such films are lower than those of single crystals. In semiconductor physics, molecular beam epitaxy (MBE) is widely established as the deposition method that produces the highest mobility structures. It is a low-energetic, high-purity technique that allows for low defect densities and precise control over doping concentrations and location. Here, we demonstrate controlled doping of epitaxial SrTiO(3) layers grown by MBE. Electron mobilities in these films exceed those of single crystals. At low temperatures, the films show Shubnikov-de Haas oscillations. These high-mobility SrTiO(3) films allow for the study of the intrinsic physics of SrTiO(3) and can serve as building blocks for high-mobility oxide heterostructures. PMID- 20364137 TI - Genome-wide association study of intracranial aneurysm identifies three new risk loci. AB - Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23 q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair. PMID- 20364140 TI - Giant solid-state barocaloric effect in the Ni-Mn-In magnetic shape-memory alloy. AB - The search for materials showing large caloric effects close to room temperature has become a challenge in modern materials physics and it is expected that such a class of materials will provide a way to renew present cooling devices that are based on the vapour compression of hazardous gases. Up to now, the most promising materials are giant magnetocaloric materials. The discovery of materials showing a giant magnetocaloric effect at temperatures close to ambient has opened up the possibility of using them for refrigeration. As caloric effects refer to the isothermal entropy change achieved by application of an external field, several caloric effects can take place on tuning different external parameters such as pressure and electric field. Indeed the occurrence of large electrocaloric and elastocaloric effects has recently been reported. Here we show that the application of a moderate hydrostatic pressure to a magnetic shape-memory alloy gives rise to a caloric effect with a magnitude that is comparable to the giant magnetocaloric effect reported in this class of materials. We anticipate that similar barocaloric effects will occur in many giant-magnetocaloric materials undergoing magnetostructural transitions involving a volume change. PMID- 20364141 TI - The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells. AB - Chromosomal instability (CIN) is a major hallmark of human cancer and might contribute to tumorigenesis. Genes required for the normal progression of mitosis represent potential CIN genes and, as such, are important tumour suppressors. The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the DNA damage response pathway. Here, we report a function of Chk2, independent of p53 and DNA damage, that is required for proper progression of mitosis, and for the maintenance of chromosomal stability in human somatic cells. Depletion of Chk2 or abrogation of its kinase activity causes abnormal mitotic spindle assembly associated with a delay in mitosis, which promotes the generation of lagging chromosomes, chromosome missegregation and CIN, while still allowing survival and growth. Furthermore, we have identified Brca1 as a mitotic target of the Chk2 kinase in the absence of DNA damage. Accordingly, loss of BRCA1 or its Chk2-mediated phosphorylation leads to spindle formation defects and CIN. Thus, the CHK2-BRCA1 tumour suppressor pathway is required for chromosomal stability, which might contribute to their tumour suppressor function. PMID- 20364142 TI - Mitotic cell-cycle progression is regulated by CPEB1 and CPEB4-dependent translational control. AB - Meiotic and early-embryonic cell divisions in vertebrates take place in the absence of transcription and rely on the translational regulation of stored maternal messenger RNAs. Most of these mRNAs are regulated by the cytoplasmic polyadenylation-element-binding protein (CPEB), which mediates translational activation and repression through cytoplasmic changes in their poly(A) tail length. It was unknown whether translational regulation by cytoplasmic polyadenylation and CPEB can also regulate mRNAs at specific points of mitotic cell-cycle divisions. Here we show that CPEB-mediated post-transcriptional regulation by phase-specific changes in poly(A) tail length is required for cell proliferation and specifically for entry into M phase in mitotically dividing cells. This translational control is mediated by two members of the CPEB family of proteins, CPEB1 and CPEB4. We conclude that regulation of poly(A) tail length is not only required to compensate for the lack of transcription in specialized cell divisions but also acts as a general mechanism to control mitosis. PMID- 20364143 TI - Control of submillisecond synaptic timing in binaural coincidence detectors by K(v)1 channels. AB - Neurons in the medial superior olive process sound-localization cues via binaural coincidence detection, in which excitatory synaptic inputs from each ear are segregated onto different branches of a bipolar dendritic structure and summed at the soma and axon with submillisecond time resolution. Although synaptic timing and dynamics critically shape this computation, synaptic interactions with intrinsic ion channels have received less attention. Using paired somatic and dendritic patch-clamp recordings in gerbil brainstem slices together with compartmental modeling, we found that activation of K(v)1 channels by dendritic excitatory postsynaptic potentials (EPSPs) accelerated membrane repolarization in a voltage-dependent manner and actively improved the time resolution of synaptic integration. We found that a somatically biased gradient of K(v)1 channels underlies the degree of compensation for passive cable filtering during propagation of EPSPs in dendrites. Thus, both the spatial distribution and properties of K(v)1 channels are important for preserving binaural synaptic timing. PMID- 20364144 TI - The exon junction complex component Magoh controls brain size by regulating neural stem cell division. AB - Brain structure and size require precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, and mechanistic explanations of how aberrant NSC division causes the reduced brain size seen in microcephaly are lacking. Here we show that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly because of INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes, as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number and genomic stability. In utero rescue experiments showed that a key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis. Our results uncover requirements for the EJC in brain development, NSC maintenance and mitosis, thereby implicating this complex in the pathogenesis of microcephaly. PMID- 20364145 TI - Neuropeptide feedback modifies odor-evoked dynamics in Caenorhabditis elegans olfactory neurons. AB - Many neurons release classical transmitters together with neuropeptide co transmitters whose functions are incompletely understood. Here we define the relationship between two transmitters in the olfactory system of C. elegans, showing that a neuropeptide-to-neuropeptide feedback loop alters sensory dynamics in primary olfactory neurons. The AWC olfactory neuron is glutamatergic and also expresses the peptide NLP-1. Worms with nlp-1 mutations show increased AWC dependent behaviors, suggesting that NLP-1 limits the normal response. The receptor for NLP-1 is the G protein-coupled receptor NPR-11, which acts in postsynaptic AIA interneurons. Feedback from AIA interneurons modulates odor evoked calcium dynamics in AWC olfactory neurons and requires INS-1, a neuropeptide released from AIA. The neuropeptide feedback loop dampens behavioral responses to odors on short and long timescales. Our results point to neuronal dynamics as a site of behavioral regulation and reveal the ability of neuropeptide feedback to remodel sensory networks on multiple timescales. PMID- 20364146 TI - Fast, single-molecule localization that achieves theoretically minimum uncertainty. AB - We describe an iterative algorithm that converges to the maximum likelihood estimate of the position and intensity of a single fluorophore. Our technique efficiently computes and achieves the Cramer-Rao lower bound, an essential tool for parameter estimation. An implementation of the algorithm on graphics processing unit hardware achieved more than 10(5) combined fits and Cramer-Rao lower bound calculations per second, enabling real-time data analysis for super resolution imaging and other applications. PMID- 20364147 TI - Optimized localization analysis for single-molecule tracking and super-resolution microscopy. AB - We optimally localized isolated fluorescent beads and molecules imaged as diffraction-limited spots, determined the orientation of molecules and present reliable formulas for the precision of various localization methods. Both theory and experimental data showed that unweighted least-squares fitting of a Gaussian squanders one-third of the available information, a popular formula for its precision exaggerates beyond Fisher's information limit, and weighted least squares may do worse, whereas maximum-likelihood fitting is practically optimal. PMID- 20364148 TI - Super-SILAC mix for quantitative proteomics of human tumor tissue. AB - We describe a method to accurately quantify human tumor proteomes by combining a mixture of five stable-isotope labeling by amino acids in cell culture (SILAC) labeled cell lines with human carcinoma tissue. This generated hundreds of thousands of isotopically labeled peptides in appropriate amounts to serve as internal standards for mass spectrometry-based analysis. By decoupling the labeling from the measurement, this super-SILAC method broadens the scope of SILAC-based proteomics. PMID- 20364149 TI - Conditional gene expression and RNAi using MEC-8-dependent splicing in C. elegans. AB - We describe a method for conditional regulation of gene expression based on the processing of an intron cassette. The RNA processing factor MEC-8 is necessary for the function of the Caenorhabditis elegans touch receptor neurons; mec-8 mutants are touch insensitive. We show here that this insensitivity involves the loss of MEC-8-dependent splicing of mec-2, which encodes a component of the mechanosensory transduction complex. MEC-8 is needed to remove the ninth intron in mec-2 pre-mRNA to form the longest of three mRNAs, mec-2a. Without MEC-8, splicing causes the termination of the transcript. Inclusion of mec-2 intron 9 is sufficient to convey mec-8-dependent regulation on other genes and, in mec 8(u218ts) mutants, resulted in their temperature-dependent expression. Because mec-8 is expressed ubiquitously in embryos and extensively in larvae, this system should produce temperature-sensitive expression for most genes. As an example, we report a strain that exhibits temperature-dependent RNA interference. PMID- 20364150 TI - Production of an antigenic peptide by insulin-degrading enzyme. AB - Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T lymphocyte recognition of tumor cells was reduced after metallopeptidase inhibition or IDE silencing. Separate inhibition of the metallopeptidase and the proteasome impaired degradation of MAGE-A3 proteins, and simultaneous inhibition of both further stabilized MAGE-A3 proteins. These results suggest that MAGE-A3 proteins are degraded along two parallel pathways that involve either the proteasome or IDE and produce different sets of antigenic peptides presented by MHC class I molecules. PMID- 20364152 TI - Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats. AB - The small (SK3) and intermediate (IK1) conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague Dawley rats (250-300 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group (P < 0.05). The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.05). Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats. PMID- 20364151 TI - HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. AB - Pattern-recognition receptors (PRRs) elicit antiviral immune responses to human immunodeficiency virus type 1 (HIV-1). Here we show that HIV-1 required signaling by the PRRs Toll-like receptor 8 (TLR8) and DC-SIGN for replication in dendritic cells (DCs). HIV-1 activated the transcription factor NF-kappaB through TLR8 to initiate the transcription of integrated provirus by RNA polymerase II (RNAPII). However, DC-SIGN signaling was required for the generation of full-length viral transcripts. Binding of the HIV-1 envelope glycoprotein gp120 to DC-SIGN induced kinase Raf-1-dependent phosphorylation of the NF-kappaB subunit p65 at Ser276, which recruited the transcription-elongation factor pTEF-b to nascent transcripts. Transcription elongation and generation of full-length viral transcripts was dependent on pTEF-b-mediated phosphorylation of RNAPII at Ser2. Inhibition of either pathway abrogated replication and prevented HIV-1 transmission. Thus, HIV-1 subverts crucial components of the immune system for replication that might be targeted to prevent infection and dissemination. PMID- 20364153 TI - Determinants of male health: the interaction of biological and social factors. AB - This review discusses the social and biological factors that may influence male development from conception to adulthood and also underlie the development of health disorders. It will provide assistance to those who may be considering the formulation of a male health policy. It aims to emphasize that social determinants function on a biological background that is profoundly influenced by a male's genome, inherited from his parents. The importance of the male-specific reproductive disorders is emphasized, but these also affect somatic structures through the secretion of androgens secreted from the testes. In turn, the function of the cardiovascular and nervous systems can significantly influence reproductive processes such as erectile dysfunction. PMID- 20364154 TI - Human prostate cancer heterotransplants: a review on this experimental model. AB - A common model used for preclinical research was in vitro human tumor cell culture. An alternative model was the direct implantation of a unique patient's tumor biopsy specimens into immunodeficient host mice. Published data from PubMed (http://www.ncbi.nlm.nih.gov) and Current Contents Connect databases (http://thomsonreuters.com/products_services/science/science_products/a z/current_contents_connect) were reviewed. Prostate cancer (PCa) heterotransplantation was evaluated using histopathology, morphology, cell differentiation, DNA content, tumor marker expression, metastases, tumor kinetics, tumor take rate and tumor vasculature in the first tumor heterotransplant. The heterotransplanted tumor retained the biological properties of the original tumor, such as morphology, degree of differentiation, pathology, secretory activity, expression of tumor markers and human vasculature. Human PCa heterotransplants have considerable experimental advantages over cell culture following xenotransplantation. PMID- 20364155 TI - A mutant of hepatitis B virus X protein (HBx Delta 127) enhances hepatoma cell migration via osteopontin involving 5-lipoxygenase. AB - AIM: To explore a novel function of a mutant of the hepatitis B virus X protein (HBx Delta 127) in the promotion of hepatoma cell migration. METHODS: The effect of HBx Delta 127 and wild type HBx on the migration ability of hepatoblastoma HepG2 cells were examined using wound healing assays in stable transfection systems. The full-length osteopontin(OPN) promoter sequence was cloned into the pGL3-Basic plasmid. The promoter activities of OPN in stably HBx Delta 127 transfected hepatoblastoma HepG2 (HepG2-X Delta 127) and hepatocellular carcinoma H7402 (H7402-X Delta 127) cells were determined using luciferase reporter gene assays. The mRNA expression levels of OPN were detected by RT-PCR. And the effect of MK886, a specific inhibitor of 5-lipoxygenase (5-LOX), on OPN promoter activity and mRNA expression in HepG2-X Delta 127 and H7402-X Delta 127 cells were examined using luciferase reporter gene assays and RT-PCR, respectively. Finally, the migration ability of HepG2-X Delta 127 was observed after treatment with siRNA targeting OPN mRNA and HBx mRNA using wound healing assays. RESULTS: HepG2-X Delta 127 cells exhibited a greater capacity for wound repair compared to HepG2-X cells. The promoter activity and mRNA expression levels of OPN were also increased in HepG2-X Delta 127 and H7402-X Delta 127 cells. Moreover, MK886 abolished the HBx Delta 127-mediated upregulation of OPN. Wound healing assays demonstrated that the migration ability of HepG2-X Delta 127 cells can be suppressed by treatment with siRNA targeting OPN mRNA and siRNA targeting HBx mRNA. CONCLUSION: HBx Delta 127 strongly promotes hepatoma cell migration via activation of OPN involving 5-LOX. PMID- 20364156 TI - Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis. AB - AIM: To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (alpha(2)AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA). METHODS: MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. RESULTS: Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 microg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 microg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. CONCLUSION: Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats. PMID- 20364157 TI - GLP-1 receptor plays a critical role in geniposide-induced expression of heme oxygenase-1 in PC12 cells. AB - AIM: To explore the role of activation of glucagon-like peptide 1 receptor (GLP 1R) and its relative cell signaling pathway in the cytoprotection of geniposide. METHODS: Cell viability was determined by MTT assay. Knockdown of the Glp-1r gene was carried out with shRNA. The levels of HO-1 protein and cAMP response element binding protein (CREB) phosphorylation were measured by Western blotting. RESULTS: Geniposide protected PC12 cells from oxidative damage induced by 3 morpholinosydnonimine hydrochloride (SIN-1) by enhancing the expression of heme oxygenase 1 (HO-1) via the cAMP-PKA-CREB signal pathway. After transfecting PC12 cells with the AB1 enhancer from the HO-1 gene, luciferase activity induced by geniposide increased in a dose-dependent manner, but not in the PC12 cells whose Glp-1r gene was disrupted. Additionally, inhibition of HO-1 activity by Sn protoporphyrin IX (SnPP) or shRNA-mediated knockdown of Glp-1r decreased the neuroprotection of geniposide in PC12 cells. CONCLUSION: GLP-1R plays a critical role in geniposide-induced HO-1 expression to attenuate oxidative insults in PC12 cells. PMID- 20364158 TI - Pharmacokinetic interactions induced by content variation of major water-soluble components of Danshen preparation in rats. AB - AIM: To investigate the pharmacokinetic interactions induced by content variation of the main water-soluble components of Danshen injection in rats. METHODS: Intravenous Danshen injection (control) or Danshen injection with danshensu (DSS), protocatechuic aldehyde (PAL), salvianolic acid A (Sal A) or salvianolic acid B (Sal B) were administered to female Sprague Dawley rats. Plasma concentrations of DSS, Sal A, PAL and its oxidative metabolite protocatechuic acid (PA) were analyzed simultaneously with LC-MS/MS; concentrations of Sal B were determined by the LC-MS method. Non-compartmental pharmacokinetic parameters were calculated and compared for identifying the pharmacokinetic interactions among these components. RESULTS: Compared with the control group, the DSS, Sal A, and Sal B groups had significant increases in AUC(0-infinity) in response to elevated concentrations of PAL (by 78.1%, 51.0%, and 82.9%, respectively), while the clearances (CL) were markedly reduced (by 42.5%, 32.9%, and 46.8%, respectively). Similarly, Sal A increased the AUC(0-infinity) of DSS and Sal B (26.7% and 82.4%, respectively) and substantially decreased their clearances (21.4% and 45.6%, respectively). In addition, the pharmacokinetics of DSS and Sal B were significantly affected by the content variation of the other major components; the AUC(0-infinity) increased by 45.1% and 52.1%, respectively, the CL dropped by 29.6% and 27.1%, respectively, and the T(1/2) was decreased by 22.0% and 19.6%, respectively. CONCLUSION: Complex, extensive pharmacokinetic interactions were observed among the major water-soluble constituents in the Danshen injection. The content variation of PAL had the most significant effect on the pharmacokinetic behaviors of other major constituents. Furthermore, the pharmacokinetics of DSS and Sal B were the most susceptible to the content change of other components. PMID- 20364159 TI - microRNAs: critical regulators in Th17 cells and players in diseases. AB - microRNAs are a novel group of small, conserved, non-coding RNA molecules that are present in all species. These molecules post-transcriptionally regulate gene expression by targeting mRNAs for degradation or by repressing the translation of the mRNAs. A good understanding of miRNA-mediated gene regulation is critical to gain a comprehensive view of many physiological processes and disease states. Emerging evidence demonstrates that miRNAs play an important role in the differentiation and function of the adaptive immune system. This review provides an overview of the diverse functions of miRNAs in modulating immune responses and in immune cell development, particularly the development of Th17 cells, and explores the involvement of miRNAs in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and diabetes. PMID- 20364161 TI - High-peak-power subnanosecond passively Q-switched ytterbium-doped fiber laser. AB - A passively Q-switched ytterbium doped fiber laser has been demonstrated with a Cr(4+):yttrium aluminum garnet saturable absorber and distributed stimulated Brillouin scattering. A linearly polarized output with approximately 375 kW peak power and a pulse duration as short as 490 ps have been obtained. A theoretical model is developed to simulate passive Q switching with the stimulated Brillouin scattering, which shows good agreement with the experiment. PMID- 20364160 TI - Multiple checkpoints keep follicular helper T cells under control to prevent autoimmunity. AB - Follicular helper T (Tfh) cells select mutated B cells in germinal centres, which can then differentiate into long-lived high affinity memory B cells and plasma cells. Tfh cells are regulated by a unique molecular programme orchestrated by the transcriptional repressor Bcl6. This transcription factor turns down expression of multiple genes, including transcriptional regulators of other T helper lineages and a vast amount of microRNAs. This enables Tfh cells to express a suite of chemokine receptors, stimulatory ligands and cytokines that enable migration into B-cell follicles, and provision of effective help to B cells. Not surprisingly, dysregulation of this powerful helper subset can lead to a range of autoantibody-mediated diseases; indeed, aberrant accumulation of Tfh cells has been linked with systemic lupus erythematosus, Sjogren's disease and autoimmune arthritis. Here we dissect multiple checkpoints that operate throughout Tfh cell development and maturation to maintain immunological tolerance while mounting robust and long-lasting antibody responses. PMID- 20364162 TI - Optical microbubble resonator. AB - We develop a method for fabricating very small silica microbubbles having a micrometer-order wall thickness and demonstrate the first optical microbubble resonator. Our method is based on blowing a microbubble using stable radiative CO(2) laser heating rather than unstable convective heating in a flame or furnace. Microbubbles are created along a microcapillary and are naturally opened to the input and output microfluidic or gas channels. The demonstrated microbubble resonator has 370 microm diameter, 2 microm wall thickness, and a Q factor exceeding 10(6). PMID- 20364163 TI - Beam waist measurement for terahertz time-domain spectroscopy experiments. AB - Classical masking aperture methods are found to be mostly inaccurate to determine the terahertz beam size in terahertz time-domain spectroscopy (TDS) experiments, owing to complex diffraction effects. Here, we present a simple and reliable method for measuring beam waists in terahertz TDS. It is based on the successive diffraction by an opaque disk followed by a small circular aperture. PMID- 20364164 TI - Transmission field enhancement of terahertz pulses in plasmonic, rectangular coaxial geometries. AB - We report on anomalous field enhancement of terahertz transmission in metallic, rectangular coaxial geometries. The integration of a particle in the hole not only results in a factor of eight increase in normalized transmittance compared to that of the hole-only counterpart, but it also tailors polarization-dependent transmission discrepancy encountered in arrays of rectangular holes. Our experimental and numerical studies on the impact of geometrical dimensions of the integrated particles indicate that dipolar localized surface plasmons of the particles contribute substantially to the terahertz field enhancement through coupling with surface plasmons and localized surface plasmons of the holes. PMID- 20364165 TI - Design and optimization of broadband wide-angle antireflection structures for binary diffractive optics. AB - We propose a class of antireflecting structures that can effectively suppress reflections for binary diffractive optics. In this structure, multiple periodic thin films with gradually varying refractive indices are used to shift all reflected diffraction to the transmitted orders. The structure is optimized to operate over broad bands and wide angles using rigorous coupled-wave analysis and genetic algorithms. We validated the structure numerically using finite difference time-domain methods. The proposed structure may lead to more efficient diffractive devices for applications in thin-film photovoltaic, waveguide coupler, and holographic optical elements. PMID- 20364166 TI - Tunable terahertz quantum cascade lasers with external gratings. AB - We demonstrate a frequency tunable external cavity terahertz quantum cascade laser using an abutted antireflection-coated silicon lens to reduce facet reflection and as a beam-forming element, with an external grating providing frequency selective optical feedback. Angle tuning of the grating allows a single longitudinal mode of the laser ridge to be selected, resulting in discontinuous tuning over a 165 GHz range around a center frequency of 4.4 THz. Another device exhibited 145 GHz of total tuning with 9 GHz of continuous tuning near the longitudinal modes of the laser. PMID- 20364167 TI - Self-stabilization of a mode-locked femtosecond fiber laser using a photonic bandgap fiber. AB - We demonstrate a self-stabilization mechanism of a semiconductor saturable absorber mode-locked linear-cavity Yb-doped fiber laser using an intracavity photonic bandgap fiber. This mechanism relies on the spectral shift of the laser pulses to a spectral range of higher anomalous dispersion and higher loss of the photonic bandgap fiber, as a reaction to the intracavity power buildup. This, in particular, results in a smaller cavity loss for the stably mode-locked laser, as opposed to the Q-switched mode-locking scenario. The laser provides stable 39-49 pJ pulses of around 230 fs duration at 29 MHz repetition rate. PMID- 20364168 TI - Femtosecond-laser-written, stress-induced Nd:YVO4 waveguides preserving fluorescence and Raman gain. AB - We report the formation of optical waveguides in the self-Raman Nd:YVO(4) laser crystal by femtosecond laser inscription. The confocal fluorescence and Raman images have revealed that the waveguide is constituted by a locally compressed area in which the original fluorescence and Raman gains of the Nd:YVO(4) system are preserved. Thus the obtained structures emerge as promising candidates for highly efficient self-Raman integrated laser sources. PMID- 20364169 TI - Coherent anti-Stokes Raman metrology of phonons powered by photonic-crystal fibers. AB - Coherent anti-Stokes Raman scattering (CARS) is used to measure the amplitude, the dephasing lifetime, and parameters of optical nonlinearities of optical phonons in a synthetic diamond film. A compact CARS apparatus demonstrated in this work relies on the use of an unamplified 70 fs 340 mW Cr:forsterite laser output and photonic-crystal fibers optimized for the generation of wavelength tunable Stokes field and the spectral compression of the probe pulse. PMID- 20364170 TI - Efficient resonantly pumped tape cast composite ceramic Er:YAG laser at 1645 nm. AB - Laser operation of a composite ceramic Er:YAG rod is demonstrated at 1645 nm with a slope efficiency of 56.9% under resonant pumping at 1532.3 nm. This is believed to be the first reported composite ceramic Er:YAG laser and also the first reported use of a tape cast technique for producing laser ceramics. PMID- 20364171 TI - Acousto-optic modulation of a point-scatterer array. AB - Acoustic modulation of light scattering from a linear centrosymmetric array is analyzed by considering far-field contributions due to optoelastic (OE) effect and acoustically induced translation of the array elements. The modulated light intensity is shown to vary sinusoidally at the acoustic frequency when the physical constants representative of the above effects are within ranges of their physical limits. The OE and translation components of the acousto-optic (AO) signal are shown to be in phase quadrature, each exhibiting a double-sided maxima when expressed as a function of the detector angle. PMID- 20364172 TI - Holographic x-ray image reconstruction through the application of differential and integral operators. AB - We introduce a noniterative image-reconstruction technique for coherent diffractive imaging. Through the application of differential and integral operators, an extended reference can be used to recover the complex-valued transmissivity of an object, in closed form, from a measurement of its far-field (Fraunhofer) diffraction intensity. We demonstrate the feasibility of this approach, using a reference of a pair of crossed wires and slits, through numerical simulations and a soft x-ray coherent diffractive imaging experiment. PMID- 20364173 TI - Magnetization-dependent loss in an (Al,Ga)As optical waveguide with an embedded Fe micromagnet. AB - The dependence of waveguiding loss on the magnetization of a Fe micromagnet embedded into the (Al,Ga)As optical waveguide was examined as a possible readout method for the spin-photon memory. The optical detection of the magnetization direction of a Fe micromagnet was demonstrated for the micromagnet sizes of 3 microm x 4 microm and 3 microm x 8 microm with signal-to-noise ratios of 4.8 and 6 dB, respectively. In the case of smaller sizes, the use of spin injection from the micromagnet into a semiconductor optical amplifier was proposed for the optical detection of the magnetization. PMID- 20364174 TI - Flexible 3D shape measurement using projector defocusing: extended measurement range. AB - A recently proposed flexible 3D shape measurement technique using a defocused projector [Opt. Lett. 34, 3080 (2009)] shows great potential because of its elimination of projector's gamma calibration. However, it cannot handle step height surfaces. I present here a technique to extend its measurement range to an arbitrary shape by integrating a binary coding method. A computational framework is also proposed to tackle the problems related to the defocusing. PMID- 20364175 TI - Optically injected quantum-dot lasers. AB - The response of an optically injected quantum-dot semiconductor laser (SL) is studied both experimentally and theoretically. In particular, the nature of the locking boundaries is investigated, revealing features more commonly associated with Class A lasers rather than conventional Class B SLs. Experimentally, two features stand out; the first is an absence of instabilities resulting from relaxation oscillations, and the second is the observation of a region of bistability between two locked solutions. Using rate equations appropriate for quantum-dot lasers, we analytically determine the stability diagram in terms of the injection rate and frequency detuning. Of particular interest are the Hopf and saddle-node locking boundaries that explain how the experimentally observed phenomena appear. PMID- 20364177 TI - Laser-treated substrate with nanoparticles for surface-enhanced Raman scattering. AB - A rapid and simple approach to fabricate a large area of nanostructured substrate for surface-enhanced Raman scattering (SERS) is reported. Gold nanoparticles ranging from 10 to 40 nm in diameter uniformly distributed on a silicon substrate were obtained by annealing the gold film precoated on the silicon substrate with UV nanosecond (ns) laser pulses. The gold nanoparticles were formed by surface tension of the melted gold layer heated by ns laser pulses. The enhancement factor of the SERS substrate for Rhodamine 6G at 632.8 nm excitation was measured to be higher than 10(5). The proposed technique provides the opportunity to equip a functional microchip with SERS capability of high sensitivity and chemical stability. PMID- 20364178 TI - Sensitive liquid refractive index sensors using tapered optical fiber tips. AB - An optical fiber sensor based on the change of optical confinement in a subwavelength tip is presented. The optical spot is substantially increased when the environmental refractive index (RI) increases from 1.3 to 1.4. By measuring the intensity of low angular spectral components, an intensity sensitivity up to 8000% per RI unit is achieved. The fiber tip sensors take advantage of the small detection volume and real-time responses. We demonstrate the application of the nanofiber sensors for measuring concentrations of acids and evaporation rates of aqueous mixtures. PMID- 20364179 TI - Reevaluation of the direct method of calculating Fresnel and other linear canonical transforms. AB - The linear canonical transform may be used to simulate the effect of paraxial optical systems on wave fields. Using a recent definition of the discrete linear canonical transform, phase space diagram analyses of the sampling requirements of the direct method of calculating the Fresnel and other linear canonical transforms are more favorable than previously thought. Thus the direct method of calculating these transforms may be used with fewer samples than previously reported simply by making use of an appropriate reconstruction filter on the samples output by the algorithm. PMID- 20364180 TI - Stable coherent beam combination by active phasing a mutual injection-locked fiber laser array. AB - We present what we believe to be a new approach for active phasing a mutual injection-locked fiber laser array. The combined advantage of active phasing and mutual injection provides a robust performance in the practical turbulent environment and high tolerance on the requirement on the laser linewidth. A proof of-concept experiment is performed by active phasing a mutually coupled laser array, and a fringe contrast of more than 79% of the in-phase intensity pattern at the receiving plane is obtained. PMID- 20364181 TI - Tuning the cavity modes of a Fabry-Perot resonator using gold nanoparticles. AB - We study the interaction between a planar Fabry-Perot microcavity and a single embedded gold nanoparticle. We record spatially resolved white-light transmission spectra and show that the interaction between microcavity and nanoparticle gives rise to a redshift of the cavity modes, in accordance with the Bethe-Schwinger cavity perturbation formula. The spectral tuning of cavity modes by discrete nanoparticles can be exploited for applications such as optical and micromechanical sensing. PMID- 20364182 TI - Sensitivity of collective plasmon modes of gold nanoresonators to local environment. AB - We present what we believe to be the first experimental study of the optical response of collective plasmon resonances in regular arrays of nanoresonators to local environment. Recently observed collective plasmon modes arise due to diffractive coupling of localized plasmons and yield almost 1 order of magnitude improvement in resonance quality. We measure the response of these modes to tiny variations of the refractive index of both gaseous and liquid media. We show that the phase sensitivity of the collective resonances can be more than 2 orders of magnitude better than the best amplitude sensitivity of the same nanodot array as well as 1 order of magnitude better than the phase sensitivity in surface plasmon resonance sensors. PMID- 20364183 TI - Microjoule-energy, 1 MHz repetition rate pulses from all-fiber-integrated nonlinear chirped-pulse amplifier. AB - We demonstrate generation of pulses with up to 4 microJ energy at 1 MHz repetition rate through nonlinear chirped-pulse amplification in an entirely fiber-integrated amplifier, seeded by a fiber oscillator. The peak power and the estimated nonlinear phase shift of the amplified pulses are as much as 57 kW and 22pi, respectively. The shortest compressed pulse duration of 140 fs is obtained for 3.1 microJ of uncompressed amplifier output energy at 18pi of nonlinear phase shift. At 4 microJ of energy, the nonlinear phase shift is 22pi and compression leads to 170-fs-long pulses. Numerical simulations are utilized to model the experiments and identify the limitations. Amplification is ultimately limited by the onset of Raman amplification of the longer edge of the spectrum with an uncompressible phase profile. PMID- 20364184 TI - Bipolar optical forces on dielectric and metallic nanoparticles by evanescent wave. AB - We numerically show that both repulsive and attractive (bipolar) optical forces can be exerted on a dielectric or metallic cylindrical nanoparticle by a totally internal refracted wave. This requires that the particles possesses either a whispering gallery (WG) resonance or a localized surface plasmon (LSP) resonance. We further explore the force spectrum that is governed by competition between the separation-dependent resonant Q factor and the coupling strength of the nanoparticle to the evanescent wave. In spite of a much smaller Q of the LSP as compare to the WG resonances, the metallic particle gains much stronger trapping force. PMID- 20364185 TI - Design of DOE for generating a needle of a strong longitudinally polarized field. AB - A needle of strong longitudinally polarized field with homogeneous intensity along the optical axis, long depth of focus, and subdiffraction beam size can be generated by focusing a radially polarized light with a high-NA lens and a diffractive optical element (DOE) with belts. A method combining the global search-optimization algorithm and the tight focusing properties of the radially polarized light is proposed to design the DOE. Based on the tight focusing properties, the light incident on the lens is divided into two parts: areas A and B. We discover that the longitudinal field in the focal region is mainly dependent on the number of belts in area B but not the total number of belts in the DOE. PMID- 20364186 TI - Power beam splitter based on photonic crystal row of holes and Brewster effect in SOI waveguides. AB - This Letter presents a beam splitter in a silicon-on-insulator (SOI) ridge waveguide loaded by a photonic crystal row of holes close to the Brewster angle. The propagation of the fundamental guided mode in this structure has been examined by the three-dimensional finite-difference time-domain method. It is shown that a TE-polarized optical beam exhibits the Brewster effect at an incident angle of about 39 degrees, giving a small splitting ratio (<0.04) in a wide spectral range for silica-filled holes with a typical diameter of 200 nm and a spacing of 300 nm. The row of holes close to the Brewster angle is the perspective to be used in developing complementary metal-oxide semiconductor compatible tunable devices based on multireflector filtering technology. PMID- 20364187 TI - Femtosecond laser-drilling-induced HgCdTe photodiodes. AB - Femtosecond-laser drilling may induce holes in HgCdTe with morphology similar to that induced by ion-milling in loophole technique. So-formed hole structures are proven to be pn junction diodes by the laser beam induced current characterization as well as the conductivity measurement. Transmission and photoluminescence spectral measurements on a n-type dominated hole-array structure give rise to different results from those of an ion-milled sample. PMID- 20364188 TI - Enhancement of third-harmonic emission from femtosecond laser filament screened partially by a thin fiber. AB - The third-harmonic (TH) emission characteristics from femtosecond laser filament, the center of which is screened by a thin metallic fiber, are experimentally investigated. The intensity of the TH emission has been enhanced for 1 order of magnitude by comparing with the undisturbed filament. The physical mechanism of the TH enhancement is analyzed to be the diffraction of the TH emission on the fiber and a redistribution of laser energy during the reconstruction of the two colored filament. These two factors can release a part of the TH energy from the filament core into the background and keep more TH energy after the termination of filament. PMID- 20364189 TI - Electromagnetically induced phase grating. AB - I propose an electromagnetically induced phase grating based on the giant Kerr nonlinearity of an atomic medium under electromagnetically induced transparency. The atomic phase grating behaves similarly to an ideal sinusoidal phase grating, and it is capable of producing a pi phase excursion across a weak probe beam along with high transmissivity. The grating is created with arbitrarily weak fields, and diffraction efficiencies as high as 30% are predicted. PMID- 20364190 TI - 1.2 mJ sub-4-fs source at 1 kHz from an ionizing gas. AB - We demonstrate a 1.2 mJ, 3.8 fs, carrier-envelope phase-controlled laser source by novel energy-scalable spectral broadening in an ionizing gas medium, which is widely applicable to sub-10-fs multimillijoule laser systems to obtain sub-2 cycle (<4 fs) multi-millijoule pulses. PMID- 20364191 TI - Optical properties of Cr2+:ZnSe single crystal and film. AB - To realize an electrically pumped compact mid-IR microlaser, the optical properties of a Cr(2+):ZnSe film deposited by rf magnetron cosputtering were compared with those of a single crystal. The mid-IR room temperature photoluminescence efficiency of the film appears only twice less than the one of the single crystal under direct (1850 nm) and indirect (458 nm) excitations. The smaller Cr(2+) fluorescence lifetime values of the film were attributed to the presence in the film of a large amount of chromium in a valence state different from Cr(2+) and of structural defects in the ZnSe host matrix. PMID- 20364192 TI - Design of multilayer diffractive optical elements with polychromatic integral diffraction efficiency. AB - What we believe to be a new method for designing multilayer diffractive optical elements (MLDOEs) for wideband with consideration of polychromatic integral diffraction efficiency (PIDE) is presented. The benefit of this method is that the maximum PIDE over the entire waveband for MLDOEs can be obtained. The design process and simulation of the MLDOEs with regard to an example for visible waveband are described, and the comparison of diffraction efficiencies of the MLDOEs for different choices of design wavelengths with different methods is given. PMID- 20364193 TI - Reflectionless potentials and cavities in waveguide arrays and coupled-resonator structures. AB - We present an approach for the realization of reflectionless potentials in linear coupled-resonator optical waveguides or optical waveguide arrays with modulated coupling. We show that soliton solutions of nonlinear Ablowitz-Ladik equations can be used to define analytically reflectionless modulations for linear photonic structures. Such structures fully transmit incident waves and simultaneously support a pair of localized modes. These results suggest new possibilities for pulse and beam shaping, including a realization of cavities that do not reflect incident light. PMID- 20364194 TI - Extraordinary infrared transmission through a periodic bowtie aperture array. AB - The discovery of extraordinary transmission through periodic aperture arrays has generated significant interest. Most studies have used circular apertures and attributed enhanced transmission to surface plasmon polariton (SPP) resonances and/or Rayleigh-Wood anomalies (RWA). Bowtie apertures concentrate light and have much longer cutoff wavelengths than circular apertures and can be designed to be strongly resonant. We demonstrate here that the total transmission through a bowtie aperture array can exceed 85% (4x the open area). Furthermore, we show that the high transmission is due to waveguide modes as opposed to the commonly believed SPP/RW phenomena. This work is focused on IR wavelengths near 9 microm; however, the results are broadly applicable and can be extended to optical frequencies. PMID- 20364195 TI - Nonlinear endomicroscopy using a double-clad fiber coupler. AB - A double-clad fiber coupler is developed to be used in two-photon-excited fluorescence endomicroscopy to replace a dichroic mirror and separate the fluorescence signal from the excitation laser beam. With the double-clad fiber coupler, the endomicroscope becomes more compact, easier to be aligned, and more stable in alignment. The double-clad fiber coupler can transmit 62% of the excitation laser beam through the core. The fluorescence collection efficiency of the double-clad fiber coupler is 34%, which is, to the best of our knowledge, the highest fluorescence collection efficiency achieved by couplers used in two photon-excited fluorescence endomicroscopes. As a result, the contrast of endomicroscopy imaging is enhanced. PMID- 20364196 TI - Comparison of raised-microdisk whispering-gallery-mode characterization techniques. AB - We compare the two prevailing raised-microdisk whispering-gallery-mode (WGM) characterization techniques, one based on coupling emission to a tapered fiber and the other based on collecting emission in the far field. We applied both techniques to study WGMs in Si nanocrystal raised microdisks and observed dramatically different behavior. We explain this difference in terms of the radiative bending loss on which the far-field collection technique relies and discuss the regimes of operation in which each technique is appropriate. PMID- 20364197 TI - Experimental realization of phase-conjugate optical coherence tomography. AB - We demonstrate phase-conjugate optical coherence tomography (PC-OCT) using a classical source of phase-sensitive cross-correlated beams to achieve measurement improvements shared by quantum OCT (Q-OCT): a factor-of-2 enhancement in axial resolution and even-order dispersion cancellation. Compared with coincidence counting used in Q-OCT, PC-OCT employs standard photodetection that results in much faster data acquisitions. This work belongs to a new class of classical techniques inspired by quantum methods that have advantages once thought to be exclusively quantum mechanical. PMID- 20364198 TI - Effect of inhomogeneous broadening on time-resolved photoluminescence in CaAlSiN3:Eu2+. AB - The decay behavior of CaAlSiN(3):Eu(2+) was monitored as a function of the detection wavelength on the Eu(2+) emission band for various Eu(2+) concentrations from 0.0005 to 0.05. The decay at the higher-energy side was faster and less linear than the lower-energy side decay for all Eu(2+) concentrations. This was due to an inhomogeneous broadening induced by the random distribution of Al and Si ions at a crystallographic site in the CaAlSiN(3) structure and to the successive site-to-site energy transfer. This phenomenon caused a redshift of the Eu(2+) emission band as the Eu(2+) concentration increased. PMID- 20364199 TI - Femtosecond laser fabricated fiber Bragg grating in microfiber for refractive index sensing. AB - Fiber Bragg grating (FBG) is fabricated in the microfiber by the use of femtosecond laser pulse irradiation. Such a grating can be directly exposed to the surrounding medium without etching or thinning treatment of the fiber, thus possessing high refractive index (RI) sensitivity while maintaining superior reliability. The grating in the microfiber may have a number of propagation modes in its transmission spectrum, depending on the fiber diameter, and the higher order of mode has larger RI sensitivity. The RI sensitivity also depends on the fiber diameter and a smaller diameter corresponds to a large sensitivity. The maximum sensitivity obtained is approximately 231.4 nm per refractive index unit at the refractive index value of approximately 1.44 when the fiber diameter is approximately 2 microm. The FBG fabricated in the microfiber has high potential in various types of optical fiber sensor applications. PMID- 20364200 TI - Multi-imaging capabilities of a 2D diffraction grating in combination with digital holography. AB - In this Letter we report on an alternative approach to get multiple images in microscopy, exploiting the capabilities of both a lithium niobate diffraction grating and digital holographic technique. We demonstrate that multi-imaging can be achieved in a lensless configuration by using a hexagonal diffraction grating but overcoming, thanks to digital holography (DH), the many constrains imposed by the grating parameters in multi-imaging with Talbot effect or Talbot array illuminators. In fact, DH permits the numerical reconstruction of the optical field diffracted by the grating, thus obtaining in-focus multiple images in a plane different from the fractional or entire Talbot ones. PMID- 20364201 TI - Integrated NiSi waveguide heaters for CMOS-compatible silicon thermo-optic devices. AB - We report the performance of NiSi-based heaters integrated with submicrometer silicon waveguides. The heaters were fabricated using a standard complementary metal-oxide-semiconductor (CMOS) silicidation process on a thin silicon slab laterally connected with a silicon rib waveguide. The intrinsic properties of such NiSi waveguide heaters were characterized by using them as thermo-optic phase shifters in a Mach-Zehnder interferometer. The power consumption P(pi) for obtaining a pi phase shift was measured to be as low as 20 mW, using CMOS compatible drive voltages. The time constant of the thermo-optic response was less than 2.8 mus. Simulations suggest that a further reduction in the power consumption P(pi) is feasible. PMID- 20364202 TI - High-power picosecond Nd:GdVO4 laser mode locked by SHG in periodically poled stoichiometric lithium tantalate. AB - Periodically poled stoichiometric lithium-tantalate is used for mode locking of a diode-pumped Nd:GdVO(4) laser by intracavity second-harmonic generation. Stable and self-starting operation is observed achieving average output powers of up to 5 W at a pulse-repetition rate of 107 MHz. The obtained pulse durations range from 6.5 ps at maximum output power down to 3.2 ps at 1.4 W. PMID- 20364203 TI - Time-resolved switching analysis of a ferroelectric liquid crystal by snapshot Mueller matrix polarimetry. AB - An experimental snapshot Mueller matrix polarimeter based on wavelength polarization coding is used to get a time-resolved description of electric-field induced fast transition within a ferroelectric liquid-crystal cell. The parameters extracted from experimental Mueller matrices are linked to the molecule director distribution to further determine the average trajectory and the collective behavior of these molecules while they switch over to another state. PMID- 20364204 TI - Size-independent low-frequency Raman scattering in Ge-nanocrystal-embedded SiO2 films. AB - The peak position and linewidth of the low-frequency Raman mode observed from amorphous silica films embedded with Ge nanocrystals doped with Si show a size independent behavior. Spectral analysis reveals the formation of a thin amorphous GeSi layer on the surface of the Ge nanocrystal. Theoretical calculation based on a modified three-region model discloses that the acoustic impedance of the interfacial GeSiO layer is responsible for the size-independent behavior. During high-temperature annealing, Ge atoms are segregated from the interface into the core, and the GeSiO interface layer is converted to SiO(2), leading to disappearance of the size-independent vibration mode. PMID- 20364205 TI - High-stability microwave frequency transfer by propagation of an optical frequency comb over 50 km of optical fiber. AB - A high-stability microwave frequency reference is transferred over 50 km of spooled optical fiber by propagation of a 90-nm-wide optical frequency comb centered at 1.56 microm. Environmentally induced fiber phase noise is actively suppressed by returning the optical frequency comb via a separate fiber. The stability of the microwave frequency delivered is measured at the "user" end, eliminating the need for the assumption of correlation between the noise in the forward and return paths. The measured transfer stability is 4.6 x 10(-15)tau( 1), rendering this technique suitable for the transfer of state-of-the-art frequency references. PMID- 20364206 TI - Phase microscopy of technical and biological samples through random phase modulation with a diffuser. AB - A technique for phase microscopy using a phase diffuser and a reconstruction algorithm is proposed. A magnified specimen wavefront is projected on the diffuser plane that modulates the wavefront into a speckle field. The speckle patterns at axially displaced planes are sampled and used in an iterative phase retrieval algorithm based on a wave-propagation equation. The technique offers a whole-field and high-resolution wavefront reconstruction of unstained microstructures. Phase maps of photoresist targets and human cheek cells are obtained to demonstrate the effectiveness of our method. PMID- 20364207 TI - Third-order aberrations of the thin refractive tunable-focus lens. AB - We present an approach to the problem of the calculation of basic paraxial parameters and the third-order aberration coefficients of thin refractive tunable focus lenses. It is shown that aberration coefficients of the third order of the thin refractive tunable-focus lens can be completely characterized by three functions that depend only on refractive indices of fluids forming the tunable focus lens and do not depend on the position and size of the object and the position of the entrance pupil. PMID- 20364208 TI - Compact fiber-optic vector inclinometer. AB - What we believe to be a novel fiber-optical inclinometer based on a dual-path core-to-cladding mode coupling mechanism is demonstrated. Both the amplitude and tilt direction of bends about a 2-mm-long flexure joint in an optical fiber can be determined. The sensor head consists of a nonadiabatic abrupt taper cascaded with a weakly tilted fiber Bragg grating. Measured bend angles of up to 12 degrees are demonstrated, as well as a method to increase the sensitivity for bend angles smaller than 4 degrees. PMID- 20364209 TI - Dual-mode optical projection tomography microscope using gold nanorods and hematoxylin-stained cancer cells. AB - An optical projection tomography microscope (OPTM) can improve axial resolution by viewing a sample from different perspectives. Here, we report a dual-mode OPTM that can generate 3D images of single cancer cells in both absorption mode and polarization mode. Cancer cells were labeled with hematoxylin for absorption imaging and nanorods for polarization imaging. Absorption images can provide morphologic information, and polarization images can provide molecular information. The combination of molecular detection and 3D cytological cell analysis may help with early cancer diagnosis. PMID- 20364210 TI - Phase unwrapping by varying the reconstruction distance in digital holographic microscopy. AB - We present a digital holographic phase-unwrapping method based on comparison of phase images obtained by using various reconstruction distances. By utilizing information from multiple reconstruction planes, this method can effectively bypass the areas of phase noise. We demonstrate that this method performs better than the traditional phase-unwrapping approaches, even in the case of a complex topology where the data contains high levels of noise. PMID- 20364211 TI - Average spreading of a Gaussian beam array in non-Kolmogorov turbulence. AB - By using the rms beam width as the parameter to characterize the spreading property, the average spreading of Gaussian beam array propagates in non Kolmogorov turbulence is studied. Numerical examples reveal that the beam width depends on the exponent value alpha, and the beam width in non-Kolmogorov turbulence is different from that in Kolmogorov turbulence with alpha=3.667. The beam width also depends on the distance between adjacent beamlets, the inner and outer scale parameters of the non-Kolmogorov turbulence. The beam array spreads more significantly with smaller inner scale and larger outer scale parameters. PMID- 20364212 TI - Polarization-switchable Q-switched DFB fiber laser. AB - A polarization switchable Q-switched distributed feedback (DFB) fiber laser is presented. This what we believe to be a new Q-switching method allows one to obtain linearly polarized laser emission in either x or y direction. The principle of this method is based on a variable birefringent phase shift induced by a lateral stress applied at a precise location along a fiber Bragg grating by a specially designed hyper-elastic device. A piezoelectric actuator controls the amount of stress delivered to the fiber, thus allowing a precise and rapid tuning of the cavity Q-factor. PMID- 20364213 TI - Space-time stereo analysis combining local structure and modulation features in the monogenic wavelet domain. AB - A multimodal cost function, based on the local multimodal image descriptors that combine local structure features (orientation, coherency) and modulation/localization information (amplitude, phase, and spatial frequency) of the monogenic wavelet transform, is proposed to estimate the time-varying disparity maps in the space-time stereo framework. The proposed cost function makes use of a constraint of local orientation, phase, and amplitude congruencies with the weighted coefficients, which are adapted to local image features and are insusceptible to level shift, scaling, and rotation and lighting invariance. Experiments on the synthetic and natural stereo sequences show the estimated results are more robust than the intensity-based sum of standard sum of squared difference cost function. PMID- 20364214 TI - Enhancing waveguided light extraction in organic LEDs using an ultra-low-index grid. AB - Improved outcoupling of light into substrate modes of an organic LED (OLED) by an ultra-low index of refraction (n=1.15), porous SiO(2) grid (UltraLIG) fabricated using glancing-angle deposition is demonstrated. Outcoupling into the substrate for electrophosphorescent tris(2-phenylpyridine) iridium [Ir(ppy)(3)]-based OLEDs grown on substrates with the UltraLIG is increased by 48% over a conventional device at a luminance of 100 cd/m(2). With efficient light outcoupling at the substrate-air interface, the UltraLIG devices attain eta(EQE)=22.5% and eta(P)=64 lm/W at their peak efficiencies, a nearly threefold increase over an analogous conventional OLED. PMID- 20364215 TI - High values of gain cross section and luminescence quantum efficiency in OH(-) free Ti3+-doped low-silica calcium aluminosilicate glass. AB - We recently reported that Ti(3+)-doped low-silica calcium aluminosilicate glass presents long luminescence lifetime (170 micros) and broad emission band (190 nm) shifted toward the visible region when compared with those from Ti(3+):sapphire single crystal and Ti(3+)-doped glasses [Phys. Rev. Lett.100, 027402 (2008)]. Here we demonstrate that this glass also shows high values of both gain cross section (approximately 4.7 x 10(-19) cm(2)) and luminescence quantum efficiency (approximately 70%). By comparing these values with those for Ti(3+):sapphire crystal, we can conclude that the studied Ti(3+)-doped glass is a promising system for tunable solid-state lasers. PMID- 20364216 TI - Dual detection full range frequency domain optical coherence tomography. AB - It has been shown that frequency domain optical coherence tomography (FD-OCT) systems achieve higher sensitivities compared to time domain optical coherence tomography (OCT) systems. However, the obscure object structure due to the mirror image generated by the Fourier transform is one of the remaining issues in the FD OCT. We designed and developed what we believe to be a novel full range FD-OCT system that we refer to as the dual detection full range frequency domain optical coherence tomography (DD-FDOCT) that enables the instantaneous retrieval of quadrature components of the complex interferometric signal. The DD-FDOCT system enables full range imaging without loss of speed, and it may be less sensitive to phase error generated by involuntary movements of the subject compared to the other established full range OCT systems, because it uses two signals with a phase difference of pi/2 obtained simultaneously from two detection arms to remove mirror images at all depths. PMID- 20364217 TI - Tunable bandpass filter based on force-induced long-period fiber grating in a double cladding fiber. AB - We present an all-fiber tunable bandpass filter based on a combination of a force induced long-period fiber grating and a fiber coil made along a double cladding fiber. The transmission wavelength can be tuned to be in a range of more than 100 nm by changing the grating period mechanically. We can control the transmission amplitude of the bandpass filter by adjusting the periodic force on the double cladding fiber. The ambient temperature causes a positive shift in the transmission wavelength. Such a device is useful for tunable laser applications and fiber-optic sensors. PMID- 20364218 TI - Validity of the V parameter for photonic quasi-crystal fibers. AB - We have investigated the validity of the V parameter to identify the single-mode operation regime for photonic quasi-crystal fibers. Our results show that the V parameter can be considered only for smoothly changing fibers. On the other hand, for fibers showing isolated high refractive regions around the core, only a mode area analysis can allow the estimation of the threshold for the single-mode operation regime. Finally, these findings can be generalized to any kind of optical fiber. PMID- 20364219 TI - 40 Gbit/s optical data exchange between wavelength-division-multiplexed channels using a periodically poled lithium niobate waveguide. AB - We propose a time- and channel-selective optical data exchange between wavelength division-multiplexed (WDM) channels by exploiting the cascaded second-order parametric nonlinear interactions in a periodically poled lithium niobate (PPLN) waveguide. It is observed that the PPLN-based optical data exchange provides nearly symmetric performance with signals located in the short- and long wavelength ranges. Optical data exchange between two WDM channels is realized with a power penalty of less than 1.5 dB at 10 Gbit/s and 3 dB at 40 Gbit/s at a bit-error rate of 10(-9). We demonstrate the 40 Gbit/s channel-selective optical data exchange between four WDM channels with a power penalty of approximately 4 dB. PMID- 20364220 TI - Suppression of mid-infrared light absorption in undoped congruent lithium niobate crystals. AB - Absorption measurements on 5 mol. % MgO-doped and undoped congruent lithium niobate (LiNbO(3)) crystals revealed absorption bands in the wavelength range of 2500-2800 nm, caused by incorporated hydrogen ions. High-temperature annealing was applied to the congruent LiNbO(3) (CLN) crystals, which decreased the absorption significantly. Then the annealed CLN crystals were periodically poled. As an application of the low-loss annealed CLN crystal, the operation of a 1550 nm pumped singly resonant CW optical parametric oscillator, resonant around 2600 nm, using a periodically poled crystal was demonstrated. PMID- 20364221 TI - Nonlinear loss dynamics in a silicon slow-light photonic crystal waveguide. AB - We directly investigate both experimentally and numerically the influence of optical nonlinear loss dynamics on a silicon waveguide based all-optical device. The dynamics of these nonlinear losses are explored through the analysis of optical limiting of an amplitude distorted 10 Gbit/s signal in a slow-light silicon photonic crystal waveguide. As the frequency of the distortion approaches the free-carrier recombination rate, free-carrier absorption reaches a steady state, leaving two-photon absorption the dominant dynamic nonlinear loss. Our results highlight the importance of engineering the free-carrier lifetime in silicon waveguides for high speed all-optical processing applications. PMID- 20364222 TI - Fixed-point numercial-reconstruction for digital holographic microscopy. AB - In this Letter, we study the reconstruction of digital holograms of microscopic objects using a fixed-point representation of the numercial-reconstruction process. For different bit levels in our fixed-point reconstruction algorithm, we investigate the errors introduced to both the reconstructed image intensity and the unwrapped quantitative phase information. Experimental results based on a microscopic lens array are provided. PMID- 20364223 TI - Saturated near-resonant refractive optical nonlinearity in CdTe quantum dots. AB - In this work, we report on an experimental investigation of the nonlinear optical properties near the first electronic resonance of thiol-capped CdTe quantum dots (QDs) being in the strong confinement regime. Using a cw laser excitation in a Z scan experimental setup, we show the presence of saturated Kerr-type nonlinear optical properties of the QDs, at low intensity levels. The large optical nonlinearity and the control of the linear and nonlinear optical properties by the size of the QDs are of special interest for applications in integrated nanophotonic devices. PMID- 20364224 TI - Phase conjugate self-organized coherent beam combination: a passive technique for laser power scaling. AB - In this Letter, a first (to our knowledge) demonstration of phase conjugate self organized coherent beam combination is reported. A demonstration involving combination of two self-adaptive gain grating holographic laser resonators is presented. Output powers of up to 27 W, with a combination efficiency of 94%, are demonstrated. This technique coherently combines individual phase conjugate laser modules, which do not have predefined spectral or spatial modes. This removes the problem of finding shared resonator modes, which should allow coherent beam combination of much larger laser arrays than standard self-organized coherent beam combination. PMID- 20364225 TI - Timing-jitter reduction of passively mode-locked fiber laser with a carbon nanotube saturable absorber by optimization of cavity loss. AB - We investigate the relationship between timing jitter and cavity loss of a passively mode-locked fiber ring laser with a carbon nanotube as a saturable absorber. It is the first time that we experimentally demonstrated the reduction of timing jitter by properly increasing laser cavity loss. The lowest timing jitter is achieved when the cavity loss is optimized. Theoretical analysis is in agreement with the experimental observations on the effect of cavity loss for the reduction of timing jitter. Moreover, it is experimentally shown that, at an optimal value of cavity loss, the timing jitter is reduced significantly by 24%, while the relative intensity noise increased by 4% only. PMID- 20364226 TI - Imaging of molecular probe activity with Born-normalized fluorescence optical projection tomography. AB - Optical projection tomography is a new ex vivo imaging technique that allows imaging of whole organs in three dimensions at high spatial resolutions. In this Letter we demonstrate its capability to tomographically visualize molecular activity in whole organs of mice. In particular, eosinophil activity in asthmatic lungs is resolved using a Born-normalized fluorescence optical projection tomography and employing a near-IR molecular probe. The possibility to achieve molecularly sensitive imaging contrast in optical projection tomography by means of targeted and activatable imaging reporter agents adds a new range of capabilities for investigating molecular signatures of pathophysiological processes and a wide variety of diseases and their development. PMID- 20364227 TI - Precision spectral manipulation of optical pulses using a coherent photon echo memory. AB - Photon echo schemes are excellent candidates for high efficiency coherent optical memory. They are capable of high-bandwidth multipulse storage, pulse resequencing and have been shown theoretically to be compatible with quantum information applications. One particular photon echo scheme is the gradient echo memory (GEM). In this system, an atomic frequency gradient is induced in the direction of light propagation leading to a Fourier decomposition of the optical spectrum along the length of the storage medium. This Fourier encoding allows precision spectral manipulation of the stored light. In this Letter, we show frequency shifting, spectral compression, spectral splitting, and fine dispersion control of optical pulses using GEM. PMID- 20364228 TI - Fabrication and characterization of silicon woodpile photonic crystals with a complete bandgap at telecom wavelengths. AB - By using direct laser writing into a novel commercially available photoresist and a silicon-double-inversion procedure followed by tempering of the silicon structures, we realize high-quality centered-tetragonal woodpile photonic crystals with complete photonic bandgaps near 1.55 microm wavelength. The 6.9% gap-to-midgap ratio bandgap is evidenced by the comparison of measured transmittance and reflectance spectra with band-structure and scattering-matrix calculations. PMID- 20364229 TI - Asynchronous detection of optical code division multiple access signals using a bandwidth-efficient and wavelength-aware receiver. AB - We experimentally demonstrate what we believe to be a novel detection scheme for interfacing asynchronous optical code division multiple access (CDMA) signals with an electronic clock and data recovery system that operates only at the baseband bandwidth. This allows using a large optical bandwidth expansion factor in which the optical chip rate is much larger than the bandwidth of the optoelectronic receiver. The received optical CDMA signal is launched into a four wave-mixing-based wavelength-aware all-optical front end that rejects multiaccess interference, followed by an amplitude-noise suppression stage comprised of a semiconductor optical amplifier. The clean signal is then converted into a non return-to-zero-like signal by a baseband receiver. Using the proposed detection scheme, asynchronous transmission and detection of optical CDMA signals is implemented. With the novel detection scheme, the classic CDMA near-far problem is mitigated, and error-free detection is easily obtained. PMID- 20364230 TI - Dual-wavelength, ultralong Raman laser with Rayleigh-scattering feedback. AB - We present experimental demonstration of a 200-km-long, dual-wavelength Raman laser utilizing two slightly different-wavelength fiber Bragg gratings, one on each side of the fiber span. The obtained results clearly prove the generation of two independent Raman lasers with a distributed "random" Rayleigh scattering mirror forming a cavity together with each of the individual fiber Bragg grating reflectors. PMID- 20364231 TI - Fluorescence tomographic microscopy by wavefront detection. AB - A new method, to our knowledge, for real-time direct access to depth information in scanning fluorescence microscopy is reported. It is based on axially exciting the sample and detecting the phase and intensity of the emitted light. Results obtained using an axicon lens to generate a Bessel beam for excitation and a microlens array as phase detector are presented. PMID- 20364232 TI - Fabrication of microfluidic channels with a circular cross section using spatiotemporally focused femtosecond laser pulses. AB - We report on the fabrication of hollow microfluidic channels with a circular cross-sectional shape embedded in fused silica by spatiotemporally focusing the femtosecond laser beam. We demonstrate both theoretically and experimentally that the spatiotemporal focusing of femtosecond laser beam allows for the creation of a three-dimensionally symmetric spherical intensity distribution at the focal spot. PMID- 20364233 TI - Cerenkov luminescence tomography for small-animal imaging. AB - Cerenkov radiation is a well-known phenomenon in which optical photons are emitted by charged particles moving faster than the speed of light in a medium. We have observed Cerenkov photons emitted from beta-emitting radiotracers such as (18)F-fluorodeoxyglucose using a sensitive CCD camera. Phantom and in vivo mouse imaging experiments have demonstrated that surface measurements of the emitted Cerenkov optical photons could be used to reconstruct the radiotracer activity distribution inside an object by modeling the optical photon propagation with the diffusion equation and reconstructing the optical emission source distribution iteratively with a preconditioned conjugate gradient method. PMID- 20364234 TI - Quantitative assessment method for computer-generated holograms free from the effect of viewpoint. AB - A quantitative assessment method for computer-generated holograms is presented. Our scheme is based on a simple evaluation quantity reflecting the optical radiating power from the holograms; this assures the overall validity of our method as a three-dimensional (3D) display assessment technique. Moreover, the effect of location from which the 3D view is observed is ruled out from the result. This contributes to both economy of computation and conciseness of the result. PMID- 20364235 TI - Spatiotemporal dynamics of cross-polarized wave generation. AB - We use time-domain spatially and spectrally resolved interferometry to investigate cross-polarized wave (XPW) generation in barium fluoride. We find that the XPW pulse is square root of 3 smaller than the input in the spatiotemporal domain, regardless of input chirp. Additionally, we calculate a temporally dependent focal length resulting from the nonlinear interaction and discuss its implications. PMID- 20364236 TI - The effects of arbuscular mycorrhizal fungal inoculation and mulch of contrasting chemical composition on the yield of cassava under humid tropical conditions. AB - The influence of arbuscular mycorrhizal fungus (AMF), Glomus deserticola, and leaf mulch from Gliricidia sepium and Senna siamea on the yield of cassava (Manihot esculenta) in a degraded alfisol of southwestern Nigeria was investigated. Inoculation in conjunction with mulching increased cassava tuber yield by 40-278% over the control. The highest yield was obtained with G. sepium and S. siamea mulch applied together in equal proportions. The results are explained in the light of the growth-enhancing effects of AMF, encouraged by the ameliorating effects of mulch on the soil structure and nutrient contents. PMID- 20364237 TI - Early events in Populus hybrid and Fagus sylvatica leaves exposed to ozone. AB - This paper aims to investigate early responses to ozone in leaves of Fagus sylvatica (beech) and Populus maximowiczii x Populus berolinensis (poplar). The experimental setup consisted of four open-air (OA) plots, four charcoal-filtered (CF) open-top chambers (OTCs), and four nonfiltered (NF) OTCs. Qualitative and quantitative analyses were carried out on nonsymptomatic (CF) and symptomatic (NF and OA) leaves of both species. Qualitative analyses were performed applying microscopic techniques: Evans blue staining for detection of cell viability, CeCl3 staining of transmission electron microscope (TEM) samples to detect the accumulation of H2O2, and multispectral fluorescence microimaging and microspectrofluorometry to investigate the accumulation of fluorescent phenolic compounds in the walls of the damaged cells. Quantitative analyses consisted of the analysis of the chlorophyll a fluorescence transients (fast kinetics). The early responses to ozone were demonstrated by the Evans blue and CeCl3 staining techniques that provided evidence of plant responses in both species 1 month before foliar symptoms became visible. The fluorescence transients analysis, too, demonstrated the breakdown of the oxygen evolving system and the inactivation of the end receptors of electrons at a very early stage, both in poplar and in beech. The accumulation of phenolic compounds in the cell walls, on the other hand, was a species-specific response detected in poplar, but not in beech. Evans blue and CeCl3 staining, as well as the multispectral fluorescence microimaging and microspectrofluorometry, can be used to support the field diagnosis of ozone injury, whereas the fast kinetics of chlorophyll fluorescence provides evidence of early physiological responses. PMID- 20364238 TI - Precipitation chemistry and occurrence of acid rain over the oil-producing Niger Delta region of Nigeria. AB - This study investigated the nitrate, sulfate, total dissolved solid (TDS), electrical conductivity, total hardness (TH), and bicarbonates of rainwater samples collected from Warri and Port Harcourt between April-June, July-August, and September-October of 2005 and 2006 to depict onset of rainy season, mid-rainy season, and end of rainy season for the two major crude oil-producing cities of the Niger Delta region of Nigeria (although Port Harcourt is also noted for non oil manufacturing industries). The same was done in Awka, a non-oil producing city in the hinterland of southeastern Nigeria. In each of the cities, rain samples were collected from three points in a triangular equilibrium using a clean plastic basin fastened to a table 2 m above ground level and 115 m away from tall buildings and trees. The parameters were determined after filtering, using their respective standard methods. Averages of 1.50, 1.81, 1.13 and 2.14, 1.50, 1.86 mg/l of nitrate for April-June, July-August, and September-October were recorded for Warri in 2005 and 2006, respectively. While 15.21, 3.23, 22.31 and 20.89, 9.96, and 14.27mg/l were recorded in Port Harcourt. Sulfate levels for Warri and Port Harcourt for the same periods are follows: 1.38, 1.88, 1.06, 1.50, 1.43, 1.50 and 2.64, 1.15, 5.88, 4.73, 1.90, 1.55 mg/l, respectively. Nitrate levels were higher than sulfate. Other parameters include TDS (5.44, 4.79, 3.30 and 7.63, 3.69, 2.56 mg/l for Warri in 2005 and 2006; 12.57, 2.07, 25.214 and 28.87, 6.73, 7.80 mg/l for Port Harcourt for the same periods). Other parameters also varied in that order for the 2 years in same cities. Crude oil exploration and gas flaring in the Niger Delta, and multiplicity of cottage industries in Awka, impacted on the inorganic ion pollution of the rainwater. This may have public health implications in the region. PMID- 20364239 TI - Sorptive removal of odorous carbonyl gases by water. AB - In this study, the removal capacity of deionized water was investigated against five gaseous carbonyl compounds (i.e., acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, and isovaleraldehyde) by means of the gas stripping method. To determine the trapping behavior of these odorants by water, gaseous working standards prepared at three different concentration levels (i.e., for acetaldehyde around 300, 500, and 1,000 ppb) were forced through pure water contained in an impinger at room temperature. The removal efficiency of the target compounds was inspected in terms of two major variables: (1) concentration levels of gaseous standard and (2) impinger water volume (20, 50, 100, and 150 mL). Although the extent of removal was affected fairly sensitively by changes in water volume, this was not the case for standard concentration level changes. Considering the efficiency of sorption media, gas stripping with aqueous solution can be employed as an effective tool for the removal of carbonyl odorants. PMID- 20364240 TI - Photoluminescent detection of dissolved underwater trace explosives. AB - A portable, rapid, and economical method for in situ trace explosive detection in aqueous solutions was demonstrated using photoluminescence. Using europium/ thenoyltrifluoroacetone as the reagent, dissolved nitroglycerin was fluorescently tagged and detected in seawater solutions without sample preparation, drying, or preconcentration. The chemical method was developed in a laboratory setting and demonstrated in a flow-through configuration using lightweight, inexpensive, commercial components by directly injecting the reagents into a continually flowing seawater stream using a small amount of organic solvent (approximately 8% of the total solution). Europium's vulnerability to vibrational fluorescence quenching by water provided the mode of detection. Without nitroglycerin in the seawater solution, the reagent's fluorescence was quenched, but when dissolved nitroglycerin was present, it displaced the water molecules from the europium/thenoyltrifluoroacetone compound and restored fluorescence. This effort focused on developing a seawater sensor, but performance comparisons were made to freshwater. The method was found to perform better in freshwater and it was shown that certain seawater constituents (such as calcium) have an adverse impact. However, the concentrations of these constituents are not expected to vary significantly from the natural seawater used herein. PMID- 20364241 TI - Nurturing holistic development of university students in Hong Kong: where are we and where should we go? AB - With reference to the mental health and developmental problems among university students, there is a need to review the university's role in nurturing holistic development of students. This paper explores the question of how holistic development of university students in Hong Kong can be promoted. Based on the positive youth development approach, it is argued that promotion of intrapersonal competencies, interpersonal relationship skills, civic responsibilities, and citizenship among university students is an important strategy to facilitate holistic development of young people in Hong Kong. Two general education or freshman seminar courses that focus on the cultivation of intrapersonal competencies, interpersonal relationship skills, civic responsibilities, and sense of citizenship among university students in Hong Kong are proposed. PMID- 20364242 TI - Lipodermatosclerosis: a commonly misdiagnosed complication of chronic venous insufficiency. PMID- 20364243 TI - A case of acute tuberculous pleuropneumonia in a patient with acute lymphoblastic leukemia. AB - Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL) when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid fast stain and culture on Lowenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol). PMID- 20364244 TI - Tubulocystic carcinoma of the kidney: a case report of natural history and long term follow-up. AB - Tubulocystic carcinoma (TC) is a rare primary renal tumor that has been recently described in the pathology literature. Formerly termed low-grade collecting duct carcinoma, further molecular analysis has shown TC to be a distinct entity that is separate from the more aggressive collecting duct carcinoma. Previous series have described the microscopic and immunohistochemical features of this tumor. We describe the natural history of this tumor in a patient who was followed with active surveillance for several years and then underwent partial nephrectomy. Long-term follow-up has shown no evidence of disease. A review of the pertinent literature is performed. PMID- 20364245 TI - Thyroid metastases from renal cell carcinoma: review of the literature. AB - The thyroid gland is a rare site of clinically detectable tumor metastasis and kidneys are frequently the site of the parent malignancy. In the present review on thyroid metastases from renal cell carcinoma, cases were searched on PubMed by entering the strings: "renal carcinoma [or "hypernephroma"] AND thyroid metastasis/metastases". Thus, we retrieved a total of 111 cases that were published between 1964 and 2007, a total that became 113 by adding two patients observed by us. The female to male ratio was 1.35:1. The primary renal cancer was almost always unilateral (90%) (with no significant side preference) and only rarely bilateral (9% in men, 4% in women), whereas bilaterality of thyroid metastases was relatively more frequent (28%). Thyroid metastasis from renal cancer was commonly single with a unique node that appears solid and hypoechoic at ultrasonography, approximately 9 years after nephrectomy. Concordance of lateralization was insignificantly greater for the right kidney/right thyroid lobe pattern (54%) than for the left kidney/left thyroid lobe pattern (40%), regardless of gender. Finally, survival was longer for women. Thyroid metastases, even if rare in the clinical practice, must be considered in the differential diagnosis of a thyroid nodule, particularly in patients who have a history of malignancies. PMID- 20364247 TI - Fate of fipronil and its metabolites in/on grape leaves, berries and soil under semi arid tropical climatic conditions. AB - Fate of fipronil and its major metabolites fipronil sulfide (MB 45950), fipronil desulfinyl (MB 46513) and fipronil sulfone (MB 46136) were studied in/on grape leaves, berries and soil. As initial residue deposits on the leaves the major component was that of fipronil, while all the 3 metabolites were also present. Among metabolites residues of MB 46513 was highest followed by MB 46136 and MB 45950. In leaves fipronil degraded faster than its metabolites. The residues of fipronil in leaves degraded at the half-life of 9.6 and 18.3 days and that of total fipronil (sum of fipronil and its metabolites) at 13.6 and 20 days, from treatment at recommended and double the recommended dose, respectively. At the time of harvest in leaves, grape berries and soil residues of fipronil and all its metabolites were below the quantifiable limit of 0.01 mg kg(-1). PMID- 20364246 TI - The predictive capacity of perceived expressed emotion as a dynamic entity of adolescents from the general community. AB - BACKGROUND: In previous studies, it has been demonstrated that high parental expressed emotion (EE) is predictive of depressive, aggressive and delinquency symptoms of adolescents. Two issues have received much less prominence in EE research, these being studies of adolescent perceived EE and the measurement of the EE as a dynamic, developmental construct. This 4-year, three-wave, longitudinal study of perceived EE of adolescents from the general community examines if adolescent perceived EE measured with the traditional, one measurement EE approach as well as adolescent perceived EE measured with a repeated measured, dynamic EE approach can predict adolescent depressive, aggressive and delinquency symptoms. METHODS: Dutch adolescents (N = 285; 51% girls; M = 13 years) from the general community were prospectively studied annually for 4 years. At all waves, the adolescents completed the Level of Expressed Emotion (LEE) questionnaire and at the final wave also completed self rated measures of depressive, aggressive and delinquent symptoms. Growth models were used to predict adolescent symptoms from adolescent perceived EE. RESULTS: Growth models significantly predicted adolescent depressive, aggressive and delinquency symptoms from adolescent perceived EE. CONCLUSIONS: This study of the LEE demonstrates that developmental characteristics of EE are predictive of adolescents' symptoms. These findings hold implications for current EE intervention therapies and the conceptualization of EE. PMID- 20364248 TI - Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine. AB - Epidemiological investigations reveal that high fluoride and low iodine have strong adverse effects on the intelligence quotient (IQ) of children. Studies also report that in some high fluoride areas, iodine deficiency also exists, especially in China. Here, with the proteomic techniques, we first report on the proteomic changes in brain proteins in offspring rats at postnatal day 20 exposed to high fluoride and/or low iodine. To investigate molecular mechanisms of central neural system injury induced by the above two elements, proteins were isolated and profiled by two-dimensional gel electrophoresis (2DE). By the analysis of Image-Master 2D Elite software, 71 protein spots in 2DE gels of treatment groups were gained and up- or down-regulated by two folds, and 5 proteins were regulated by five folds, with the comparison to the control group. The proteins changed by five folds were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The identified proteins are mainly related with cellular signaling, energy metabolism, and protein metabolism and provide a valuable clue to explore the mechanism underlining the neurotoxicity of high fluoride and low iodine. Moreover, these results could provide potential biomarkers for hazards caused by excessive fluoride and low iodine. PMID- 20364249 TI - A membrane-proximal region in the C-terminal tail of NHE7 is required for its distribution in the trans-Golgi network, distinct from NHE6 localization at endosomes. AB - Mammalian Na(+)/H(+) exchanger (NHE) isoform NHE6 is localized in sorting/recycling endosomes, whereas NHE7 is localized in the trans-Golgi network (TGN) and mid-trans-Golgi stacks. The mechanism targeting each NHE to a specific organelle is largely unknown, although the targeting is thought to be important for pH control in the lumen of various organelles. NHE6 and NHE7 exhibit distinct localization despite conserved amino acid sequences. To specify the intramolecular region involved in the specific localization, we examined the intracellular localization of chimeric NHE6 and NHE7 constructs. NHEs are composed of an N-terminal transmembrane domain (TM) and a C-terminal hydrophilic tail domain (Ct). Exchange of the Ct between the isoforms suggested that the Ct is required for the specific localization. We further split the Ct into three regions, and chimeras with various combinations of these small regions indicated that the most membrane-proximal region among the three contributes to the specific localization. Mutant forms of NHE7 with sequential alanine substitutions in the most membrane-proximal region, between residues 530 and 589, showed that two regions (residues 553-559 and 563-568) are required for NHE7-like localization. However, NHE6 with alanine substitutions in the membrane-proximal region exhibited no apparent change in localization. These results suggest that two membrane proximal regions (residues 533-559 and 563-568) play an important role in targeting NHE7 to the TGN. PMID- 20364250 TI - Heterotrophic bone formation with bone marrow in the kidney parenchyme. AB - Extraosseous metaplasia of the urinary tract is an uncommon condition first described in 1923 by Phemister. Bone formation can occur anywhere along the urinary tract but most has been described in renal pelvis, calyx or along the urothelial layer. We report a case of extraossesous bone formation within the kidney parenchyma appearing as a calcified multiseptated mass. PMID- 20364251 TI - 2,4,5-trichlororophenol and its derivatives induce biochemical and morphological changes in human peripheral blood lymphocytes in vitro. AB - In this work, the investigation of the effects of 2,4,5-trichlorophenol (2,4,5 TCP), 4,6-dichloroguaiacol (4,6-DCG), and 4,5-dichlorocatechol (4,5-DCC) on selected morphological and biochemical parameters in human peripheral blood lymphocytes were studied. All of the investigated compounds (at concentrations from 25-600 ppm) increased the size and granularity of the lymphocytes. 2,4,5-TCP induced the strongest and 4,5-DCC induced the weakest changes in these parameters. Moreover, 2,4,5-TCP induced the greatest loss of lymphocyte viability, which was statistically significant at concentrations of 125 and 600 ppm. DNA and protein damage was provoked by relatively low concentrations of the xenobiotics examined. Comet assay analysis showed that 4,6-DCG and 4,5-DCC at 5 ppm significantly increased the level of single- and/or double-strand breaks in the DNA of human lymphocytes. The increase in carbonyl group content (the marker of protein damage) was more strongly induced by 4,5-DCC and 2,4,5-TCP than by 4,6 DCG at concentrations ranging from 0.04 to 5 ppm. DNA and protein damage was most probably caused by reactive oxygen species (ROS) because it was observed that all of the compounds studied, as well as 4,5-DCC and 2,4,5-TCP in particular, were capable of oxidising fluorescent probe 6-carboxy-2',7'-dichlorodihydrofluorescein at very low concentrations (0.01-1 ppm). In summary, 2,4,5-TCP induced the greatest morphological and cytotoxic changes in human peripheral blood lymphocytes, whereas its metabolite 4,5-DCC caused the most severe biochemical alterations, such as protein and DNA damage as well as ROS formation, in the incubated cells,. PMID- 20364252 TI - Tissue injury and cellular immune responses to cadmium chloride exposure in the common mussel Mytilus edulis: modulation by lipopolysaccharide. AB - The immunotoxic effects of cadmium (Cd) exposure in bivalves are poorly understood and whether or not stimulation of the immune system exacerbates Cd toxicity is unclear. The mussel Mytilus edulis was exposed to 20 or 50 MUg/l total Cd for up to 11 days compared to no added Cd controls to assess immune and other physiological responses. Selected experiments were then repeated in the presence of a lipopolysaccharide (LPS) challenge with and without subsequent Cd exposure. Immune functions of hemocytes, hematology, hemolymph glucose and ion content, as well as superoxide dismutase (SOD) activity and organ pathology were measured. Cd accumulated mainly in digestive gland and gills and to a lesser extent in the adductor muscle. Exposure to 20 MUg/l Cd alone caused a transient modulated of phagocytosis and increased neutral red retention (Kruskal-Wallis, p = 0.002). The higher Cd concentration also increased cytotoxicity, and decreased hemocyte count. Changes in hemolymph Na(+), K(+), and glucose were small or negligible. Histopathological examination showed tissue injuries consistent with inflammation and necrosis in the gills, digestive gland, and adductor muscle during Cd exposure alone. LPS injection alone and LPS + Cd caused an increase in the number of circulating hemocytes by the end of the experiment (Kruskal-Wallis, p = 0.01) and a transient rise in phagocytosis at day 4 (analysis of variance (ANOVA), p = 0.001). The LPS + Cd treatment also caused transient changes in neutral red retention and in the cytotoxicity of hemocytes compared to controls. Intracellular SOD activity did not change in hemocytes under any treatment. Tissue inflammation and pathology was greatly increased by the effect of Cd exposure with an LPS injection compared to either treatment alone. We conclude that immunostimulation with LPS can greatly increase Cd-related organ pathologies but does not necessarily alter the responses of hemocytes. PMID- 20364253 TI - Preoperative assessment of intestinal endometriosis: A comparison of transvaginal sonography with water-contrast in the rectum, transrectal sonography, and barium enema. AB - To evaluate the accuracy of Transrectal Sonography (TRS) and a new technique, Transvaginal Sonography with Water-Contrast in the Rectum (RWC-TVS), in the diagnosis of rectosigmoid endometriosis, and the accuracy of Barium Enema (BE) and RWC-TVS in the detection of intestinal stenosis due to endometriosis. In a prospective study, we compared the findings of TRS and RWC-TVS performed before surgery with the operative and pathologic findings in 61 consecutive patients who underwent laparoscopy or laparotomy for suspected rectosigmoid endometriosis. The accuracy of BE and RWC-TVS in the detection of intestinal stenosis was evaluated comparing the radiologic and ultrasonographic results with the macroscopic findings at surgery and pathology. RWC-TVS diagnosed rectosigmoid endometriosis with the same accuracy of TRS and was equally efficient as BE in the detection of a significant intestinal lumen stenosis. For the diagnosis of rectosigmoid endometriosis the sensitivity, specificity, positive and negative predictive values of TRS and RWC-TVS were 88.2% and 96%, 80%, and 90%, 95.7%, and 98%, and 57.1% and 81.8%, respectively. For the detection of intestinal stenosis the sensitivity, specificity, positive and negative predictive values of BE and RWC TVS were 93.7% and 87.5%, 94.2% and 91.4%, 88.2% and 82.3%, and 97% and 94.1%, respectively. RWC-TVS is a new, simple technique for a single-step and accurate preoperative assessment of rectosigmoid endometriosis. PMID- 20364254 TI - The perceived implications of an outsourcing model on governance within British Columbia Provincial Parks in Canada: a quantitative study. AB - Good governance is of paramount importance to the success of parks and protected areas. This research utilized a questionnaire for 10 principles of governance to evaluate the outsourcing model used by British Columbia Provincial Parks, where profit-making corporations provide all front country visitor services. A total of 246 respondents representing five stakeholder groups evaluated the model according to each principle, using an online survey. Principal component analysis resulted in two of the 10 principles (equity and effectiveness) each being split into two categories, leading to 12 governance principles. Five of the 12 criteria received scores towards good governance: effectiveness outcome; equity general; strategic vision; responsiveness; and effectiveness process. One criterion, public participation, was on the neutral point. Six criteria received scores below neutral, more towards weak governance: transparency; rule of law; accountability; efficiency; consensus orientation; and, equity finance. The five stakeholder groups differed significantly on 10 of the 12 principles (P < .05). The 2 exceptions were for efficiency and effectiveness process. Seven of the 12 criteria followed a pattern wherein government employees and contractors reported positive scores, visitors and representatives of NGOs reported more negative scores, and nearby residents reported mid-range scores. Three criteria had government employees and contractors reporting the most positive scores, residents and visitors the most negative scores, and NGO respondents reporting mid-range scores. This research found evidence that perceptions of governance related to this outsourcing model differed significantly amongst various constituent groups. PMID- 20364255 TI - The bone marrow lesion in osteoarthritis. AB - Osteoarthritis (OA) is considered a multifactorial disease whose development and progression may include several structural abnormalities aside from cartilage destruction. Bone marrow lesions (BMLs) have been reported to be associated with OA pathology, and several studies have advocated its close connection to the severity of joint structural alterations and pain, the main OA clinical manifestation. Hence, BMLs may not only affect subchondral bone and its neuronal and vascular structures but also negatively influence the adjacent tissues. Here, we analyze the pathophysiology and natural history of OA-associated BMLs and their potential relevance to the radiographic progression and severity of the disease. The notion that BMLs may be a precursor to additional articular abnormalities, can be a potential risk factor for development of OA, and may serve as an additional diagnostic tool and a therapeutic target are further discussed. PMID- 20364256 TI - Solitary osseous sarcoidosis: a rare reason for pathologic fracture. AB - Sarcoidosis with osseous involvement as the initial manifestation is rare. Due to lack of other organ involvements, the diagnosis is somehow difficult to establish. We report a case with osseous sarcoidosis as the initial and major manifestation that developed spontaneous bone fracture. Our case emphasizes the importance of histological evidence and exclusion of other diseases i.e. rheumatoid arthritis, before making the diagnosis of osseous sarcoidosis. PMID- 20364257 TI - Stress and developmental responses of terpenoid biosynthetic genes in Cistus creticus subsp. creticus. AB - Plants, and specially species adapted in non-friendly environments, produce secondary metabolites that help them to cope with biotic or abiotic stresses. These metabolites could be of great pharmaceutical interest because several of those show cytotoxic, antibacterial or antioxidant activities. Leaves' trichomes of Cistus creticus ssp. creticus, a Mediterranean xerophytic shrub, excrete a resin rich in several labdane-type diterpenes with verified in vitro and in vivo cytotoxic and cytostatic activity against human cancer cell lines. Bearing in mind the properties and possible future exploitation of these natural products, it seemed interesting to study their biosynthesis and its regulation, initially at the molecular level. For this purpose, genes encoding enzymes participating in the early steps of the terpenoids biosynthetic pathways were isolated and their gene expression patterns were investigated in different organs and in response to various stresses and defence signals. The genes studied were the CcHMGR from the mevalonate pathway, CcDXS and CcDXR from the methylerythritol 4-phosphate pathway and the two geranylgeranyl diphosphate synthases (CcGGDPS1 and 2) previously characterized from this species. The present work indicates that the leaf trichomes are very active biosynthetically as far as it concerns terpenoids biosynthesis, and the terpenoid production from this tissue seems to be transcriptionally regulated. Moreover, the CcHMGR and CcDXS genes (the rate limiting steps of the isoprenoids' pathways) showed an increase during mechanical wounding and application of defence signals (like meJA and SA), which is possible to reflect an increased need of the plant tissues for the corresponding metabolites. PMID- 20364258 TI - Improvement of histopathological classification of adrenal gland tumors by genetic differentiation. AB - PURPOSE: There are often problems in differentiating between benign and malignant adrenal gland tumors by imaging and histopathology. Fine-needle biopsy is possible but not used owing to problems in histopathological differentiation. On account of considerable differences in the therapy and aftercare of benign and malignant adrenal tumors, correct classification of tumor type is of greatest importance. The purpose of this study was to define specific genetic alterations differentiating between adenomas and carcinomas. METHODS: DNA was isolated from tumor areas in paraffin sections and amplified by a modified protocol for DOP PCR. After labeling of tumor-DNA and normal DNA with biotin-dUTP and digoxigenin dUTP, respectively, comparative genomic hybridization (CGH) was carried out according to standard protocols. Retrospectively, 26 (16 adenomas and 10 carcinomas) tumors of the adrenal cortex were analyzed. RESULTS: Genetic alterations were found in 5/16 adenomas (31.25%) and in all adrenocortical carcinomas. The mean number of genetic changes per tumor was 8.7 (range 6-12) in carcinomas. The benign cortical tumors present 1.6 changes (range 0-3) per tumor. Only a moderate correlation between number of alterations and size of tumor was seen. Furthermore, specific chromosomal alterations of carcinomas were identified. CONCLUSIONS: Genetic evaluation facilitates differentiation between adrenal gland tumors. Genetic tests should be used in routine diagnostics of adrenal specimens. Potentially, fine-needle biopsy can be established as standard diagnostics of adrenal tumors with unknown genesis. PMID- 20364260 TI - LXR activation inhibits chemokine-induced CD4-positive lymphocyte migration. AB - Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that CD4-positive lymphocytes express the nuclear transcription factors Liver-X-Receptor (LXR) alpha and beta with an effect of LXR activators on TH1-cytokine release from these cells. However, the role of LXR in lymphocyte migration remains currently unexplored. Therefore, the present study investigated whether LXR activation might modulate chemokine induced migration of these cells. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.5 +/- 0.8-fold increase in cell migration (P < 0.05; n = 12). Pretreatment of cells with the LXR activator T0901317 reduces this effect in a concentration-dependent manner to a maximal 0.9 +/- 0.4-fold induction at 1 micromol/L T0901317 (P < 0.05 compared to SDF-1-treated cells; n = 12). Similar results were obtained with the LXR activator GW3965. The effect of LXR activators on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, T0901317 inhibited activation of the small GTPase Rac and phosphorylation of the myosin light chain (MLC). Moreover, LXR activator treatment reduced f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Transfection of CD4-positive lymphocytes with LXRalpha/beta siRNA abolished T0901317 inhibitory effect on MLC phosphorylation and ICAM3 translocation. LXR activation by T0901317 or GW3965 inhibits chemokine-induced migration of CD4 positive lymphocytes. Given the crucial importance of chemokine-induced T cell migration in early atherogenesis, LXR activators may be promising tools to modulate this effect. PMID- 20364259 TI - Prognostic factors in renal cell carcinoma. AB - PURPOSE: Renal cell carcinoma (RCC) is a very heterogeneous disease with widely varying prognosis. An accurate knowledge of the individual risk of disease progression and mortality after treatment is essential to counsel patients, plan individualized surveillance protocols and select patients for adapted treatment schedules and new clinical trials. METHODS: A systematic review of the literature on prognostic factors of localized and metastatic RCC was performed. RESULTS: Prognostic factors in RCC include anatomical (TNM classification, tumor size), histological (Fuhrman grade, histologic subtype), clinical (symptoms and performance status), and molecular features. All these features are not perfectly accurate when used alone. Therefore an increasing number of prognostic models or nomograms that include several combined prognostic features have been designed in order to improve predictive accuracy. UCLA Integrated Staging System (UISS) and the Mayo Clinic's SSIGN score are the two most used prognostic models for localized RCC. In the setting of metastatic RCC the classical anatomical and histological tumor features have little predictive value. However, accurate prognostic models have been designed to predict response to therapy, and progression-free and overall survival. The two most used tools to predict response to immunotherapy are the model designed by the French Group of Immunotherapy and the Motzer's model. The advent of tyrosine kinase inhibitors and antiangiogenic drugs have deeply changed the treatment of metastatic RCC. Predictive tools that are adapted to the modern targeted therapies are now needed. CONCLUSION: There is increasing knowledge on prognostic factors of localized and metastatic RCC. Several predictive models have been developed by combining different prognostic features and are valuable tools for patient counseling, treatment decision-making and trial design. Further research is needed to assess whether the combination of classical prognostic factors with molecular features and information from gene and protein expression profiling can increase the predictive accuracy of the current prognostic models. PMID- 20364261 TI - Clinical and radiological long-term results after operative treatment of chondroblastoma. AB - INTRODUCTION: The aim of this study was the investigation of radiological and clinical long-term results after surgery for chondroblastoma in a single orthopedic oncological center. METHOD: As much as 24 patients were enrolled in the study using an in-house tumor data-base (age, sex, patient history, clinical symptoms, type of surgery, complications, and histological results), radiological findings (localization/size of the lesion, Lodwick-classification, Enneking stages, and local recurrence), and clinical investigation (Enneking score). Mean follow-up was 8 years. RESULTS: Preferred sites were the knee-joint (distal femur 6, proximal tibia 6), followed by the proximal humerus (8), and the proximal femur. As much as 3 lesions were judged inactive, 13 active, and 8 aggressive. Apart from one case, all lesions were treated by curettage and filling of the defect by bone cement and/or cancellous bone chips. Only one patient suffered local recurrence after primary resection of the tumor (4.2%). About 87.5% of our patients reached a very good or good functional result (Enneking score 28-30). CONCLUSION: Our results further support curettage and defect filling even of active/aggressive chondroblastoma. If performed betimes, the surgical therapeutic concept of accurate intralesional curettage with or without local adjuvant therapy and defect packing with cancellous bone grafts and/or bone cement assures a high chance of joint preservation along with a low rate of recurrence and good functional long-term results. PMID- 20364262 TI - Saturday night palsy or Sunday morning hangover? A case report of alcohol-induced Crush Syndrome. AB - Saturday night palsy is a colloquial term given to brachial plexus injuries of the arm resulting from stretching or direct pressure against a firm object, often after alcohol or drug consumption. In most circumstances, this condition gives rise to a temporary plexopathy, which generally resolves. However, if the compression is severe and prolonged, a more grave form of this condition known as 'Crush Syndrome' may occur. Skeletal muscle injury, brought about by protracted immobilization, leads to muscle decay, causing rhabdomyolysis, which may in turn precipitate acute renal failure. This condition is potentially fatal and has an extremely high morbidity. The case presented below demonstrates the drastic consequences that can result following an episode of 'binge' drinking in a young man. What is most concerning is that this trend is increasing across society and cases like this may not be as rare in the future. PMID- 20364263 TI - Percutaneous screw fixation of acetabular fractures with 2D fluoroscopy-based computerized navigation. AB - INTRODUCTION: The treatment of displaced acetabular fractures with formal open reduction and internal fixation has gained general acceptance. However, extensile exposure can lead to complications. Two-dimensional fluoroscopy-based computerized navigation for placement of percutaneous screw across non-displaced acetabular fractures has attracted interest by making use of stored patient specific imaging data to provide real-time guidance in multiple image planes during implant placement. The purpose of the present study was to document early treatment results and complications associated with this new technique and evaluate its clinical application to displaced acetabular fractures amenable to closed or limited open reduction. MATERIALS AND METHODS: Eighteen adult patients with 12 non-displaced and 8 displaced acetabular fractures were treated with percutaneous screw fixation under the guidance of a fluoroscopy-based navigation system. There were 14 men and four women with a mean age of 42.1 years (range 19 54 years). According to the AO and Orthopaedic Trauma Association Classification, there were nine 62-A3, five 62-B1, three 62-B2, and three 62-B3. The mean follow up was 21 months (range 12-28 months). The mean time from injury to surgery was 4 days (range 2-7 days). RESULTS: A total of 30 acetabular screws were inserted, including 21 anterior column screws and 9 posterior column screws. The average operation time was 24.6 min (range 16-47 min) from the image acquisition to wound closure. The average fluoroscopic time was 28.4 s (range 11-58 s). Compared to the final position of the screw, the average deviated distance of wire tip was 2.5 mm (range 1.1-3.6 mm) and the average trajectory difference was 2.45 degrees (range 1.5 degrees -4.6 degrees ). Maximal gap displacement averaged 10 mm (range 2-22 mm) preoperatively and 3 mm (range 0-5 mm) postoperatively; while maximal step displacement averaged 4 mm (range 1-10 mm) preoperatively and 2 mm (range 0 4 mm) postoperatively. One patient sustained a transient femoral nerve palsy and resolved 2 months after the operation. No superficial or deep infection occurred. Using the rating system of D'Aubigne and Postel, 13 patients had excellent results, 4 patients had good results, and 1 patient had a fair result. CONCLUSION: Percutaneous screw fixation of acetabular fractures with 2D fluoroscopy-based navigation could be applied not only to non-displaced fractures but also to displaced fractures amenable to closed or limited open reduction. PMID- 20364264 TI - Tests of shielding effectiveness of Kevlar and Nextel onboard the International Space Station and the Foton-M3 capsule. AB - Radiation assessment and protection in space is the first step in planning future missions to the Moon and Mars, where mission and number of space travelers will increase and the protection of the geomagnetic shielding against the cosmic radiation will be absent. In this framework, the shielding effectiveness of two flexible materials, Kevlar and Nextel, were tested, which are largely used in the construction of spacecrafts. Accelerator-based tests clearly demonstrated that Kevlar is an excellent shield for heavy ions, close to polyethylene, whereas Nextel shows poor shielding characteristics. Measurements on flight performed onboard of the International Space Station and of the Foton-M3 capsule have been carried out with special attention to the neutron component; shielded and unshielded detectors (thermoluminescence dosemeters, bubble detectors) were exposed to a real radiation environment to test the shielding properties of the materials under study. The results indicate no significant effects of shielding, suggesting that thin shields in low-Earth Orbit have little effect on absorbed dose. PMID- 20364265 TI - Are these data real? Comments on "No effects of intermittent 50 Hz EMF on cytoplasmic free calcium and on the mitochondrial membrane potential in human diploid fibroblasts." by Pilger et al. (Radiat Environ Biophys 43:203-7 (2004)). PMID- 20364266 TI - Lung function and health status in metropolitan fire-fighters compared to general population controls. AB - PURPOSE: To assess health status of South Australian (SA) metropolitan fire fighters in terms of lung function and health-related quality of life, compare these with general population controls, and explore associations between fire fighters' self-reported occupational exposure and health status. METHODS: The study was a cross-sectional comparison of (respiratory) health indices between 501 fire-fighters and 1,324 general population controls taken from the North West Adelaide Health Study (NWAHS). All were men aged 21 to 61. Measurements included spirometry (i.e., forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), mid-expiratory flow (FEF(25-75)) and the Short Form 36 (SF-36) health related quality of life questionnaire. RESULTS: Health status in the fire fighters was generally better than in NWAHS controls. Mean % predicted FEV(1) and FVC were 103.4% [SD 12.1] versus 89.5% [13.7] and 110.0% [11.6] versus 88.5% [12.5] (both p < 0.001 in linear regression analysis, adjusted for age, smoking, BMI, and FEV(1) % predicted). FEV(1)/FVC and FEF(25-75) were significantly lower in the fire-fighters (p < 0.003). A total of 93 (18.6%) fire-fighters and 82 (6.2%) controls had an FEV(1)/FVC < 70% (p < 0.001). The SF-36 Mental Health scale was the only scale on which fire-fighters had a lower mean score (p = 0.009), but none of the SF-36 scales showed clinically meaningful differences between the cohorts. Fire-fighters exposed > 6 h/week to dust, smoke, and fire showed lower FEV(1), FEV(1) % predicted, and FVC values compared to those who were less exposed (p < 0.05). CONCLUSIONS: Male metropolitan fire-fighters showed better general health, better lung health, and similar mental health compared to general population controls. The high rate of fire-fighters with FEV(1)/FVC values below the recommended cut-point for airflow obstruction illustrates the inappropriateness of this clinical cut-point for use in populations preselected on their physical fitness. The observed dose-effect relationship between self reported occupational exposure and fire-fighters' lung function warrants further investigation. PMID- 20364267 TI - Closer correlation of cadmium in urine than that of cadmium in blood with tubular dysfunction markers in urine among general women populations in Japan. AB - OBJECTIVES: The objectives of the present study are to investigate whether cadmium in blood (Cd-B) and cadmium in urine (Cd-U) correlate with each other irrespective of age among general populations and which one of Cd-B or Cd-U correlates more closely with three renal tubular dysfunction markers in urine of alpha1-microglobulin (alpha1-MG-U), beta2-microglobulin (beta2-MG-U) and N-acetyl beta-D-glucosaminidase (NAG-U). METHODS: Data on two exposure markers (Cd-B and Cd-U) and three effect markers (alpha1-MG-U, beta2-MG-U and NAG-U) were collected for 1,403 adult women in non-polluted areas all over Japan. Possible significance of correlation between the parameters and dependency on age was examined by simple and multiple regression analysis. RESULTS: Both Cd-B and Cd-U increased as a function of age. The two exposure markers correlated significantly with each other, and the Cd-U over Cd-B ratio also increased as a function of age. Although both Cd-B and Cd-U correlated significantly with the three effect markers, the correlation was closer for Cd-U than for Cd-B. CONCLUSIONS: Cd-U rather than Cd-B should be recommended as an exposure marker of choice in Cd biological monitoring of general populations. Effects of aging should be taken into account when evaluating study results. PMID- 20364268 TI - Increasing stimulus intensity does not affect sensorimotor synchronization. AB - When people synchronize taps with isochronously presented stimuli, taps usually precede the pacing stimuli [negative mean asynchrony (NMA)]. One explanation of NMA [sensory accumulation model (SAM), Aschersleben in Brain Cogn 48:66-79, 2002] is that more time is needed to generate a central code for kinesthetic-tactile information than for auditory or visual stimuli. The SAM predicts that raising the intensity of the pacing stimuli shortens the time for their sensory accumulation, thereby increasing NMA. This prediction was tested by asking participants to synchronize finger force pulses with target isochronous stimuli with various intensities. In addition, participants performed a simple reaction time task, for comparison. Higher intensity led to shorter reaction times. However, intensity manipulation did not affect NMA in the synchronization task. This finding is not consistent with the predictions based on the SAM. Discrepancies in sensitivity to stimulus intensity between sensorimotor synchronization and reaction-time tasks point to the involvement of different timing mechanisms in these two tasks. PMID- 20364269 TI - A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle. AB - Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype-phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 x 10(-6)) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 x 10(-6)), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2. PMID- 20364270 TI - Geographic and temporal correlations of mammalian size reconsidered: a resource rule. AB - The tendency of mammals to increase or decrease body size with respect to geography or time depends on the abundance, availability, and size of resources. This dependency accounts for a change in mass with respect to geography, including latitude (Bergmann's rule), a desert existence, and life on oceanic islands (the island rule), as well as in a seasonal anticipation of winter (Dehnel's phenomenon) and a tendency for some lineages to increase in mass through time (Cope's rule). Such a generalized pattern could be called the "resource rule," reflecting the controlling effect of resource availability on body mass and energy expenditure. The correlation of mammalian size with geography and time reflects the impact of temperature, rainfall, and season on primary production, as well as the necessity in the case of some species to share resources with competitors. The inability of the constituent "rules" to account for all size trends often results from unique patterns of resource availability. PMID- 20364271 TI - Hydraulic lift through transpiration suppression in shrubs from two arid ecosystems: patterns and control mechanisms. AB - Hydraulic lift (HL) is the passive movement of water through the roots from deep wet to dry shallow soil layers when stomata are closed. HL has been shown in different ecosystems and species, and it depends on plant physiology and soil properties. In this study we explored HL patterns in several arid land shrubs, and developed a simple model to simulate the temporal evolution and magnitude of HL during a soil drying cycle under relatively stable climatic conditions. This model was then used to evaluate the influence of soil texture on the quantity of water lifted by shrubs in different soil types. We conducted transpiration suppression experiments during spring 2005 in Chile and spring 2008 in Spain on five shrub species that performed HL, Flourensia thurifera, Senna cumingii and Pleocarphus revolutus (Chile), Retama sphaerocarpa and Artemisia barrelieri (Spain). Shrubs were covered with a black, opaque plastic fabric for a period of 48-72 h, and soil water potential was recorded at different depths under the shrubs. While the shrubs remained covered, water potential continuously increased in shallow soil layers until the cover was removed. The model output indicated that the amount of water lifted by shrubs is heavily dependent on soil texture, as shrubs growing in loamy soils redistributed up to 3.6 times more water than shrubs growing on sandy soils. This could be an important consideration for species growing in soils with different textures, as their ability to perform HL would be context dependent. PMID- 20364272 TI - Drought-deciduous behavior reduces nutrient losses from temperate deciduous trees under severe drought. AB - Nutrient resorption from senescing leaves is an important mechanism of nutrient conservation in temperate deciduous forests. Resorption, however, may be curtailed by climatic events that cause rapid leaf death, such as severe drought, which has been projected to double by the year 2100 in the eastern United States. During a record drought in the southeastern US, we studied 18 common temperate winter-deciduous trees and shrubs to understand how extreme drought affects nutrient resorption of the macronutrients N, P, K, and Ca. Four species exhibited drought-induced leaf senescence and maintained higher leaf water potentials than the remaining 14 species (here called drought-evergreen species). This strategy prevented extensive leaf desiccation during the drought and successfully averted large nutrient losses caused by leaf desiccation. These four drought-deciduous species were also able to resorb N, P, and K from drought-senesced leaves, whereas drought-evergreen species did not resorb any nutrients from leaves lost to desiccation during the drought. For Oxydendrum arboreum, the species most severely affected by the drought, our results indicate that trees lost 50% more N and P due to desiccation than would have been lost from fall senescence alone. For all drought-deciduous species, resorption of N and P in fall-senesced leaves was highly proficient, whereas resorption was incomplete for drought-evergreen species. The lower seasonal nutrient losses of drought-deciduous species may give them a competitive advantage over drought-evergreen species in the years following the drought, thereby impacting species composition in temperate deciduous forests in the future. PMID- 20364274 TI - Rehabilitation program for prosthetic tracheojejunal voice production and swallowing function following circumferential pharyngolaryngectomy and neopharyngeal reconstruction with a jejunal free flap. AB - The case of a 68-year-old woman with postoperative speech and swallowing problems following a circumferential pharyngolaryngectomy and neopharyngeal reconstruction with a jejunal free flap is presented. The primary tumor was an extended papillary thyroid carcinoma (pT4N0M0). For vocal restoration, an indwelling Provox((r)) 1 voice prosthesis was inserted secondarily. The patient received speech and swallowing therapy, including digital maneuvers at the level of the proximal (cervical) part of the jejunal graft to improve speech and swallowing function. Pre- and/ or post-treatment data on speech and swallowing function were gathered using the following assessment methods: esophageal insufflation test, Voice Handicap Index (VHI), videofluoroscopy of phonation (VFSph), digital high speed endoscopy of jejunal vibration during voice production, fiber-optic endoscopic evaluation of swallowing (FEES), and videofluoroscopy of swallowing (VFSs). This case clearly demonstrates that even after extensive laryngopharyngectomy with jejunal free flap reconstruction, a tailored rehabilitation program can improve both voice and swallowing function, and that these results clearly can be objectified/visualized, underlining the validity of this approach. PMID- 20364275 TI - Takotsubo cardiomyopathy associated with nonepileptic seizure after percutaneous endoscopic lumbar discectomy under general anesthesia. AB - Nonepileptic seizures are rare complication after general anesthesia. Postoperative seizure-induced oxidative stress promotes acute catecholamine toxicity of the myocardium. Takotsubo cardiomyopathy may be more frequent in the perioperative setting than commonly appreciated. We report a case of nonepileptic seizure developed during emergence from general anesthesia. The patient subsequently developed takotsubo cardiomyopathy. We now clearly recognize that patients with seizure activities after general anesthesia may be a higher risk for takotsubo cardiomyopathy. PMID- 20364276 TI - The long-term functional outcome of type II odontoid fractures managed non operatively. AB - Odontoid fractures currently account for 9-15% of all adult cervical spine fractures, with type II fractures accounting for the majority of these injuries. Despite recent advances in internal fixation techniques, the management of type II fractures still remains controversial with advocates still supporting non rigid immobilization as the definitive treatment of these injuries. At the NSIU, over an 11-year period between 1 July 1996 and 30 June 2006, 66 patients (n = 66) were treated by external immobilization for type II odontoid fractures. The medical records, radiographs and CT scans of all patients identified were reviewed. Clinical follow-up evaluation was performed using the Cervical Spine Outcomes Questionnaire (CSOQ). The objectives of this study were to evaluate the long-term functional outcome of patients suffering isolated type II odontoid fractures managed non-operatively and to correlate patient age and device type with clinical and functional outcome. Of the 66 patients, there were 42 males and 24 females (M:F = 1.75:1) managed non-operatively for type II odontoid fractures. The mean follow-up time was 66 months. Advancing age was highly correlated with poorer long-term functional outcomes when assessing neck pain (r = 0.19, P = 0.1219), shoulder and arm pain (r = 0.41, P = 0.0007), physical symptoms (r = 0.25, P = 0.472), functional disability (r = 0.24, P = 0.0476) and psychological distress (r = 0.41, P = 0.0007). Patients >65 years displayed a higher rate of pseudoarthrosis (21.43 vs. 1.92%) and established non-union (7.14 vs. 0%) than patients <65 years. The non-operative management of type II odontoid fractures is an effective and satisfactory method of treating type II odontoid fractures, particularly those of a stable nature. However, patients of advancing age have been demonstrated to have significantly poorer functional outcomes in the long term. This may be linked to higher rates of non-union. PMID- 20364277 TI - Molecular characterization of a Hungarian isolate of Tobacco necrosis virus A. PMID- 20364278 TI - Fibronectin and asialoglyprotein receptor mediate hepatitis B surface antigen binding to the cell surface. AB - Both fibronectin and the asialoglycoprotein receptor (ASGPR) have been identified by some investigators as partners for hepatitis B virus (HBV) envelope proteins. Because fibronectin is a natural ligand for ASGPR, we speculated that HBV might attach to ASGPR expressed on the hepatocyte surface via fibronectin. To test this hypothesis, we first confirmed by co-immunoprecipitation that ASGPR, fibronectin and HBsAg bind to each other in HepG2.2.15 cells, and possible binding domains were identified by GST pull-down. In addition, by measuring binding of HBsAg to cells, we found that ASGPR and fibronectin enhanced the binding capability of HBsAg to HepG2 cells, and even to 293T and CHO cells, which normally do not bind HBV. In conclusion, our findings suggest that both fibronectin and ASGPR mediate HBsAg binding to the cell surface, which provides further evidence for the potential roles of these two proteins in mediating HBV binding to liver cells. PMID- 20364279 TI - Lactic acid bacterial cell factories for gamma-aminobutyric acid. AB - Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to. PMID- 20364280 TI - Quantitative proteome analysis of the 20S proteasome of apoptotic Jurkat T cells. AB - Regulated proteolysis plays important roles in cell biology and pathological conditions. A crosstalk exists between apoptosis and the ubiquitin-proteasome system, two pathways responsible for regulated proteolysis executed by different proteases. To investigate whether the apoptotic process also affects the 20S proteasome, we performed three independent SILAC-based quantitative proteome approaches: 1-DE/MALDI-MS, small 2-DE/MALDI-MS and large 2-DE/nano-LC-ESI-MS. Taking the results of all experiments together, no quantitative changes were observed for the alpha- and beta-subunits of the 20S proteasome except for subunit alpha7. This protein was identified in two protein spots with a down regulation of the more acidic protein species (alpha7a) and up-regulation of the more basic protein species (alpha7b) during apoptosis. The difference in these two alpha7 protein species could be attributed to oxidation of cysteine-41 to cysteine sulfonic acid and phosphorylation at serine-250 near the C terminus in alpha7a, whereas these modifications were missing in alpha7b. These results pointed to the biological significance of posttranslational modifications of proteasome subunit alpha7 after induction of apoptosis. PMID- 20364281 TI - Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+) and water coordination on the structure and properties of L-histidine and zwitterionic L histidine. AB - Interactions between metal ions and amino acids are common both in solution and in the gas phase. The effect of metal ions and water on the structure of L histidine is examined. The effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+) and water on structures of His.M(H2O)m, m=0.1 complexes have been determined theoretically employing density functional theories using extended basis sets. Of the five stable complexes investigated the relative stability of the gas-phase complexes computed with DFT methods (with one exception of K+ systems) suggest metallic complexes of the neutral L-histidine to be the most stable species. The calculations of monohydrated systems show that even one water molecule has a profound effect on the relative stability of individual complexes. Proton dissociation enthalpies and Gibbs energies of L-histidine in the presence of the metal cations Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+ were also computed. Its gas-phase acidity considerably increases upon chelation. Of the Lewis acids investigated, the strongest affinity to L-histidine is exhibited by the Cu2+ cation. The computed Gibbs energies DeltaG are negative, span a rather broad energy interval (from -130 to -1,300 kJ/mol), and upon hydration are appreciably lowered. PMID- 20364282 TI - From sulfur to homoglutathione: thiol metabolism in soybean. AB - Sulfur is an essential plant nutrient and is metabolized into the sulfur containing amino acids (cysteine and methionine) and into molecules that protect plants against oxidative and environmental stresses. Although studies of thiol metabolism in the model plant Arabidopsis thaliana (thale cress) have expanded our understanding of these dynamic processes, our knowledge of how sulfur is assimilated and metabolized in crop plants, such as soybean (Glycine max), remains limited in comparison. Soybean is a major crop used worldwide for food and animal feed. Although soybeans are protein-rich, they do not contain high levels of the sulfur-containing amino acids, cysteine and methionine. Ultimately, unraveling the fundamental steps and regulation of thiol metabolism in soybean is important for optimizing crop yield and quality. Here we review the pathways from sulfur uptake to glutathione and homoglutathione synthesis in soybean, the potential biotechnology benefits of understanding and modifying these pathways, and how information from the soybean genome may guide the next steps in exploring this biochemical system. PMID- 20364283 TI - Femoral neck geometry in overweight and normal weight adolescent girls. AB - Being overweight is associated with increased bone mineral content, bone mineral density (BMD), and bone strength in adults. However, the effect of being overweight on bone strength during adolescence is poorly understood. The aim of this study was to compare femoral neck geometry in overweight and normal weight adolescent girls. This study included 22 overweight (BMI > 25 kg/m(2)) adolescent girls (15.4 +/- 2.4 years old) and 20 maturation-matched (15.2 +/- 1.9 years old) controls (BMI < 25 kg/m(2)). Body composition and BMD were assessed by dual energy X-ray absorptiometry (DXA). To evaluate bone geometry, DXA scans were analyzed at the femoral neck by the hip structure analysis (HSA) program. Cross sectional area (CSA), an index of axial compression strength, section modulus (Z), an index of bending strength, cross-sectional moment of inertia (CSMI), cortical thickness (CT), and buckling ratio (BR) were measured from bone mass profiles. Lean mass, body weight, fat mass, and BMI were higher in overweight girls compared to controls (P < 0.001). CSA, Z, and CSMI were higher in overweight girls compared to controls (P < 0.05; P < 0.01 and P < 0.01, respectively). CT and BR were not significantly different between the two groups. After adjustment for body weight, lean mass, or fat mass, using a one-way analysis of covariance (ANCOVA), there were no differences between the two groups (overweight and controls) regarding the HSA variables (CSA, Z, CSMI, CT, and BR). In conclusion, this study suggests that overweight adolescent girls have greater indices of bone axial and bending strength in comparison to controls at the femoral neck. PMID- 20364284 TI - Concomitant management of a large abdominal aortic aneurysm and a giant incarcerated inguinal hernia. AB - The optimal therapeutic approach to a patient who has a large incarcerated inguinal hernia and an abdominal aortic aneurysm (AAA) of significant size is controversial. Here we report a case of a patient who presented with a giant incarcerated inguinal hernia who was found to have an 8-cm AAA. Three surgical options were considered: (1) perform open AAA repair first, followed by hernia repair a few weeks later to allow for recovery, (2) perform hernia repair first followed by AAA repair a few weeks later, or (3) perform both simultaneously as a combination procedure. We successfully performed hernia repair first, followed by open AAA repair as a separate procedure at a later date. We believe that a two stage approach, performing hernia repair first, is the safest approach to surgical repair of an incarcerated hernia in a patient with an asymptomatic AAA that requires open repair. PMID- 20364285 TI - Current topics on therapeutic apheresis. AB - Remarkable advances have been made in the area of pharmacotherapy such as immunosuppressants and biologics in recent years. However, there is always the possibility that adequate pharmacotherapy cannot be carried out due to resistance, organ damage, allergies, and adverse drug reactions. The idea of aiming for treatment that is safer and more effective by using concomitant therapeutic apheresis to mitigate drug therapies that cause severe tissue injury has surfaced. In the present report, I would like to discuss new findings related to disorders such as rheumatoid arthritis, ulcerative colitis, and chronic hepatitis C that are already covered by insurance and the indications, methods, and clinical efficacy of therapeutic apheresis for disorders such as dilatative cardiomyopathy, pyoderma gangrenosum, and pulmonary fibrosis that are currently being evaluated and investigated in the hope that they will be covered in the future. PMID- 20364286 TI - Preliminary studies for the development of a second generation granulocytapheresis (G-CAP) column. AB - The preliminary studies for developing a second generation granulocytapheresis (G CAP) column were made. In the past, the G-CAP column has been used for the treatment of ulcerative colitis and rheumatoid arthritis. However, recent clinical studies have revealed that the therapeutic effects of the G-CAP column are not significant compared with those of the sham column. These results were considered to be due to insufficient reduction of granulocytes. Thus, development of a better granulocyte removal column was attempted. Realizing that white cells adhered on small-diameter synthetic fibers of 1-2 microm, small diameter cotton fibers were subjected to the studies of their granulocyte-removing capabilities. Three types of cotton, Pakistani, Australian and Egyptian cottons, were evaluated using normal human blood in vitro. Miniature columns were made of each fiber, and CBC and WBC differentiation was compared between pre- and post-filtered blood. The Egyptian cotton removed leukocytes, especially granulocytes, the most efficiently of the three types of cotton. The Egyptian cotton's granulocyte adhesion properties were not altered after different chemical treatments. A 4-ml column of packaged Egyptian cotton with a density of more than 0.125 g/ml could remove granulocytes effectively up to 80 ml of blood passages. Based upon these studies, second generation G-CAP could be carried out with Egyptian cotton fibers as a scaled-up clinical module. PMID- 20364287 TI - High-dose carvedilol therapy for mechanical circulatory assisted patients. AB - Left ventricular assist devices are increasingly being used as a "bridge to recovery" in the clinical arena. However, the percentage of patients who can be weaned off these devices is still low. Carvedilol is an anti-heart failure agent that is used to induce cardiac reverse remodeling, and its effect is reportedly dose-dependent. In this study, we conducted high-dose carvedilol therapy (80 mg daily) in five patients who wore left ventricular assist devices. Three of the five patients showed an increase in cardiac function after this therapy, and one patient was successfully weaned off his device. No major adverse events were observed. The high-dose carvedilol therapy was found to be a safely tolerated intervention that may have enhanced the reverse remodeling of the failing heart in patients with left ventricular assist devices. PMID- 20364288 TI - Resource use and costs of treating acute cough/lower respiratory tract infections in 13 European countries: results and challenges. AB - The objectives of this study were to estimate the resource use and cost of treating acute cough/lower respiratory tract infection (acute cough/LRTI) in 13 European countries, to explore reasons for differences in cost and to document the challenges that researchers face when collecting information on cost alongside multinational studies. Data on resource use and cost were collected alongside an observational study in 14 primary care networks across 13 European countries and a mean cost was generated for each network. The results show that the mean cost (standard deviation) of treating acute cough/LRTI in Europe ranged from euro23.88 (34.67) in Balatonfured (Hungary) to euro116.47 (34.29) in Jonkoping (Sweden). The observed differences in costs were statistically significant (P < 0.01). Major cost drivers include general practitioner visits and drug costs in all networks, whilst differences in health systems and regional factors could account for differences in cost between networks. The major barrier to conducting multinational cost studies are barriers associated with identifying cost information. PMID- 20364289 TI - Practical issues in handling data input and uncertainty in a budget impact analysis. AB - The objective of this paper was to address the importance of dealing systematically and comprehensively with uncertainty in a budget impact analysis (BIA) in more detail. The handling of uncertainty in health economics was used as a point of reference for addressing the uncertainty in a BIA. This overview shows that standard methods of sensitivity analysis, which are used for standard data set in a health economic model (clinical probabilities, treatment patterns, resource utilisation and prices/tariffs), cannot always be used for the input data for the BIA model beyond the health economic data set for various reasons. Whereas in a health economic model, only limited data may come from a Delphi panel, a BIA model often relies on a majority of data taken from a Delphi panel. In addition, the dataset in a BIA model also includes forecasts (e.g. annual growth, uptakes curves, substitution effects, changes in prescription restrictions and guidelines, future distribution of the available treatment modalities, off-label use). As a consequence, the use of standard sensitivity analyses for BIA data set might be limited because of the lack of appropriate distributions as data sources are limited, or because of the need for forecasting. Therefore, scenario analyses might be more appropriate to capture the uncertainty in the BIA data set in the overall BIA model. PMID- 20364290 TI - Control of genic DNA methylation in Arabidopsis. AB - Detailed features of genomic DNA methylation have been revealed by recent genome wide analyses on several model organisms. An unexpected feature conserved among plants and some animals is the presence of DNA methylation within transcribed genes. For understanding the controlling mechanisms of the enigmatic genic methylation, genetic and genomic approaches using Arabidopsis may be effective. PMID- 20364291 TI - Spontaneous outer retinal closure of stage 1B macular hole without vitreofoveal separation. AB - A 65-year-old patient complained of central metamorphopsia and presented an intraretinal cyst with a yellow ring in the fovea of the right eye. His best corrected visual acuity was 20/32 in that eye. Optical coherence tomography (OCT) 3 showed an enlarged pseudocyst at the outer retina of a stage 1B macular hole; the foveal roof was intact where the vitreous was attached reflecting a perifoveal posterior vitreous detachment. Six months later, OCT 3 showed bridging by centripetal protrusion in the outer fovea inside the pseudocyst with a residual defect in the foveal photoreceptor layer. Eighteen months after the initial visit, spectral-domain OCT showed bridging of the outer retina inside the pseudocyst at the hyper-reflective line representing the external limiting membrane; the roof of the pseudocyst was more elevated with posterior hyaloid adhesion and there was a smaller residual defect in the foveal photoreceptor layer. This case demonstrates that spontaneous closure in the outer retina may develop in some cases of stage 1B macular holes without vitreofoveal separation. PMID- 20364292 TI - Construction of an L-phenylalanine-producing tyrosine-prototrophic Escherichia coli strain using tyrA ssrA-like tagged alleles. AB - To construct a Phe-producing Tyr(+) Escherichia coli strain, TyrA (chorismate mutase/prephenate dehydrogenase) activity was varied by engineering a proteolytically unstable protein. The tyrA in the E. coli BW25113 was altered to include ssrA-like tags. The tagged tyrA genes, which ensured different growth rates in M9 medium, were introduced into a Phe-producing strain to replace DeltatyrA. Strains with unstable TyrA-(A)ANDENYALAA proteins had a lower biomass yield and a higher Phe accumulation than strains generating the more stable TyrA (A)ANDENYALDD. The Tyr/Phe ratio produced by the TyrA-tag strains was 10-fold less than that produced by the TyrA(wt) strain. PMID- 20364293 TI - Purification and characterization of an acid phosphatase from Trichoderma harzianum. AB - An acid phosphatase from Trichoderma harzianum was purified in a single step using a phenyl-Sepharose chromatography column. A typical procedure showed 22 fold purification with 56% yield. The purified enzyme showed as a single band on SDS-PAGE with an apparent molecular weight of 57.8 kDa. The pH optimum was 4.8 and maximum activity was obtained at 55 degrees C. The enzyme retained 60% of its activity after incubation at 55 degrees C for 60 min. The K (m) and V (max) values for p-nitrophenyl phosphate (p-NPP) as a substrate were 165 nM and 237 nM min(-1), respectively. The enzyme was partially inhibited by inorganic phosphate and strongly inhibited by tungstate. Broad substrate specificity was observed with significant activities for p-NPP, ATP, ADP, AMP, fructose 6-phosphate, glucose 1-phosphate and phenyl phosphate. PMID- 20364294 TI - High transesterification activities of immobilized proteases in new ether functionalized ionic liquids. AB - Three new ether-functionalized hydrophobic ionic liquids (ILs) were synthesized. Two proteases (subtilisin and alpha-chymotrypsin both covalently immobilized on chitosan) exhibited high synthetic activity (1-3 micromol/min x g) and selectivity (>97-99%, esterification over hydrolysis) in these ILs containing 10 15% (v/v) water during the transesterification of N-acetyl-L-phenylalanine ethyl ester with 1-propanol. However, the same reaction in t-butanol or [BMIM][Tf(2)N], with water contents higher than 2% (v/v) yielded low synthetic activities (0.2-1 micromol/min g in t-butanol) and/or poor selectivity (<40%). The high synthetic activities of proteases in ether-functionalized ILs at high water contents are explained by two reasons: (1) the hydrogen-bond donors in ILs (R(1)-O-R(2)) and chitosan (-OH) controlling the thermodynamic water activity of the reaction system, and (2) the protective role of the ether chain in reducing the cation protein interaction. PMID- 20364295 TI - Rapid detection of virulence stx2 gene of Enterohemorrhagic Escherichia coli using two-step ultra-rapid real-time PCR. AB - A rapid detection method for Enterohemorrhagic Escherichia coli (EHEC), which has the virulent stx2 gene, was developed using a two-step, ultra-rapid real-time (URRT) PCR. URRT PCR was designed to detect the stx2 gene using a microchip based, real-time PCR system, GenSpector TMC-1000, which only has a 6 microl total reaction volume with an extremely short denaturation step and combined annealing/extension step (1 and 3 s, respectively) for each cycle. Specific primers for the stx2 gene were designed to amplify a 100 bp region known for genetic stability among the various EHEC strains. Using the URRT PCR method, stx2 gene could be detected in 7 min 8 s including melting point (Tm) analysis. The detection limit for the stx2 gene for URRT-PCR was estimated to be 3 c.f.u./PCR with the amplification product having a consistent Tm of 85.2 +/- 0.4 degrees C. This method was tested for the various applications relevant to the different EHEC strains and was useful for the rapid detection of stx2-carrying EHEC strains. PMID- 20364296 TI - Fluorescent 3-hydroxy-4-pyridinone hexadentate iron chelators: intracellular distribution and the relevance to antimycobacterial properties. AB - We report the synthesis and characterization of a fluorescent iron chelator (4), shown to be effective in inhibiting the growth of Mycobacterium avium in macrophages, together with the synthesis and characterization of two unsuccessful analogues selected to facilitate identification of the molecular properties responsible for the antimicrobial activity. Partition of the chelators in liposomes was investigated and the compounds were assessed with respect to uptake by macrophages, responsiveness to iron overload/iron deprivation and intracellular distribution by flow cytometry and confocal microscopy. The synthesis of the hexadentate chelators is based on a tetrahedral structure to which three bidentate 3-hydroxy-4-pyridinone chelating units are linked via amide bonds. The structure is synthetically versatile, allowing further addition of functional groups such as fluorophores. Here, we analyse the non-functionalized hexadentate unit (3) and the corresponding rhodamine B (4) and fluorescein (5) labelled chelators. The iron(III) stability constant was determined for 3 and the values log beta = 34.4 and pFe(3+) = 29.8 indicate an affinity for iron of the same order of magnitude as that of mycobacteria siderophores. Fluorescence properties in the presence of liposomes show that 4 strongly interacts with the lipid phase, whereas 5 does not. Such different behaviour may explain their distinct intracellular localization as revealed by confocal microscopy. The flow cytometry and confocal microscopy studies indicate that 4 is readily engulfed by macrophages and targeted to cytosol and vesicles of the endolysosomal continuum, whereas 5 is differentially distributed and only partially colocalizes with 4 after prolonged incubation. Differential distribution of the compounds is likely to account for their different efficacy against mycobacteria. PMID- 20364297 TI - A chimeric satellite transgene sequence is inefficiently targeted by viroid induced DNA methylation in tobacco. AB - In plants, transgenes containing Potato spindle tuber viroid (PSTVd) cDNA sequences were efficient targets of PSTVd infection-mediated RNA-directed DNA methylation. Here, we demonstrate that in PSTVd-infected tobacco plants, a 134 bp PSTVd fragment (PSTVd-134) did not become densely methylated when it was inserted into a chimeric Satellite tobacco mosaic virus (STMV) construct. Only about 4-5% of all cytosines (Cs) of the PSTVd-134 were methylated when flanked by satellite sequences. In the same plants, C methylation was approximately 92% when the PSTVd 134 was in a PSTVd full length sequence context and roughly 33% when flanked at its 3' end by a 19 bp PSTVd and at its 5' end by a short viroid-unrelated sequence. In addition, PSTVd small interfering RNAs (siRNAs) produced from the replicating viroid failed to target PSTVd-134-containing chimeric STMV RNA for degradation. Satellite RNAs appear to have adopted secondary structures that protect them against RNA interference (RNAi)-mediated degradation. Protection can be extended to short non-satellite sequences residing in satellite RNAs, rendering them poor targets for nuclear and cytoplasmic RNAi induced in trans. PMID- 20364298 TI - Growth inhibition, morphology change, and cell cycle alterations in NFBD1 depleted human esophageal cancer cells. AB - NFBD1/MDC1 is a large nuclear protein mainly participating in DNA damage response, indicating its therapeutic potential as a radio-/chemosensitizer target in cancer field. Esophageal cancer ranks among one of the most frequent cause of cancer death in the world. In this study, we used three representative esophageal cancer cell lines to investigate the effects of NFBD1 silencing on cell proliferation, cell morphology, and cell cycle distribution. Synthetic small interfering RNA (siRNA) duplexes against NFBD1 were introduced into three esophageal cancer cell lines, which subsequently resulted in a significant inhibition in NFBD1 expression in the cells. Our results have shown that a targeted siRNA depletion of NFBD1 resulted in a significant growth inhibition, morphology change, and cell cycle alterations in esophageal cancer cells. Furthermore, NFBD1 depletion also sensitized all the three esophageal cancer cell lines to chemotherapeutic agents including adriamycin and cisplatin. Taken together, our study strongly suggested that NFBD1 may serve as a potential therapeutic target in human esophageal cancer. PMID- 20364299 TI - Wound repair and anti-oxidative capacity is regulated by ITGB4 in airway epithelial cells. AB - Integrin beta 4 (ITGB4) is a structural adhesion molecule which engages in maintaining the integrity of airway epithelial cells. Its specific cytomembrane structural feature strongly indicates that ITGB4 may engage in many signaling pathways and physiologic processes. However, in addition to adhesion, the specific biologic significance of ITGB4 in airway epithelial cells is almost unknown. In this article, we investigated the expression and functional properties of ITGB4 in airway epithelial cells in vivo and in vitro. Human bronchial epithelial cell line (16HBE14O-cells) and primary rat tracheal epithelial cells (RTE cells) were used to determine ITGB4 expression under ozone tress or mechanical damage, respectively. An ovalbumin (OVA)-challenged asthma model was used to investigate ITGB4 expression after antigen exposure in vivo. In addition, an ITGB4 overexpression vector and ITGB4 silence virus vector were constructed and transfected into RTE cells. Then, wound repair ability and anti oxidation capacity was evaluated. Our results demonstrated that, on the edge of mechanically wounded cell areas, ITGB4 expression was increased after mechanical injury. After ozone stress, upregulation expression of ITGB4 was also detected. In the OVA-challenged asthma model, ITGB4 expression was decreased on airway epithelial cells accompanying with structural disruption and damage of anti oxidation capacity. Besides, our study revealed that upregulation of ITGB4 promotes wound repair ability and anti-oxidative ability, while such abilities were blocked when ITGB4 was silenced. Taken together, these results showed that ITGB4 was a new interesting molecule involved in the regulation of wound repair and anti-oxidation processes for airway epithelial cells. PMID- 20364301 TI - Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer. AB - To investigate the potential role of small breast epithelial mucin (SBEM) as a marker for detecting hematogenous micrometastasis in breast cancer and explore its clinical significance in neoadjuvant chemotherapy. SBEM protein expression in 82 tissue specimens of primary breast cancer was detected using immunohistochemistry (IHC), and SBEM expression in peripheral blood (PB) samples of 109 primary breast cancer patients (94 cases at stage I-III, 15 cases at stage IV) was detected by flow cytometry (FCM) and reverse transcription polymerase chain reaction (RT-PCR). Moreover, SBEM mRNA expression was monitored by quantification real-time PCR (QPCR) before and after 3 cycles' neoadjuvant chemotherapy. SBEM expression correlated with tumor node metastasis (TNM) staging and lymph node metastasis at both mRNA and protein levels. SBEM expression in PB of breast cancer patients was markedly higher than that of healthy donors and other cancer patients. SBEM was found expressed in PB of 50 cases among 94 cases at stage I-III and expressed in PB of 11 cases among 15 cases at stage IV. After 3 cycles' neoadjuvant chemotherapy, SBEM expression levels were significantly down-regulated in up to 58% breast cancer patients. SBEM has the potential to be a specific marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer. PMID- 20364300 TI - Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population. AB - The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD. PMID- 20364302 TI - Fluorescence labelling of DNA by carboxylic polypyridyl-Ru complexes containing bpy and DIP ligands: a study revisited. AB - The coordination complexes (DIP)(2)Ru(CH(3)bpyCOOH) and (DIP)(2)Ru(COOHbpyCOOH), where DIP and bpy are diphenylphenanthroline and bispyridine, have been recently proposed as fluorescent markers of nuclear DNA (Musatkina et al., J. Inorg. Biochem. 101:1086-1089, 2007), but no DNA binding investigation and no quantitative fluorescence evaluations had been done. Both complexes, as well as the smaller ones with bpy's in place of DIP's, have been investigated here by spectroscopic DNA titrations (UV-vis absorption, fluorescence, circular dichroism) and by in vitro cellular studies (flow cytometry and fluorescence imaging). Contrary to previous reports, neither the carboxylic function nor the more extended DIP ligand ensures any appreciable binding to DNA. This is clearly illustrated by the appearance of an isosbestic point of a second kind and by the proportionality of the fluorescence maximum intensity to the absorbance at the excitation wavelength. Above all, the lack of enhanced fluorescence in the presence of DNA definitively rules out the use of such complexes as DNA markers. Moreover, there is no detectable nuclear uptake. However, the fluorescent complexes with the DIP ligands, especially (DIP)(2)Ru(CH(3)bpyCOOH), are massively incorporated into the cytoplasm while preserving cell integrity, which could suggest other types of biological application. PMID- 20364303 TI - Recent incarceration linked to cutaneous injection-related infections among active injection drug users in a Canadian setting. AB - Cutaneous injection-related infections (CIRI), such as abscesses and cellulitis, are the cause of a substantial burden of morbidity and mortality among injection drug users (IDU). The possible contribution of exposure to correctional environments to CIRI risk has not been fully investigated. Thus, we sought to test the possible relationship between incarceration and CIRI using data from a community-based sample of IDU. Data for these analyses was from the Scientific Evaluation of Supervised Injecting (SEOSI) cohort, linked with administrative records of a local ED in Vancouver, Canada. Using longitudinal analysis we assessed the relationship between the number of ED visits for CIRI care and recent incarceration in a multivariate model including information on possible confounders. Between June 2004 and December 2006, 901 individuals were eligible for our analysis. Of these, 214 (9.6%) visited the ED for CIRI care at least once during the study period. The incidence of ED care for CIRI was 72.9 per 100 person years. In a multivariate model, recent incarceration was associated with a greater number of ED visits for CIRI care (adjusted relative rate = 1.56, 95% confidence interval: 1.31-1.85, P < 0.001). The need for ED treatment for CIRI was common among a sample of local IDU. Exposure to correctional environments was an independent risk factor for visiting the ED for CIRI care, suggesting improvements in infection control in local prisons is urgently needed. PMID- 20364304 TI - The relationship among sexual attitudes, sexual fantasy, and religiosity. AB - Recent research on the impact of religiosity on sexuality has highlighted the role of the individual, and suggests that the effects of religious group and sexual attitudes and fantasy may be mediated through individual differences in spirituality. The present study investigated the role of religion in an ethnically diverse young adult sample (N = 1413, 69% women) using religious group as well as several religiosity domains: spirituality, intrinsic religiosity, paranormal beliefs, and fundamentalism. Differences between religious groups in conservative sexual attitudes were statistically significant but small; as predicted, spirituality mediated these effects. In contrast to the weak effects of religious group, spirituality, intrinsic religiosity, and fundamentalism were strong predictors of women's conservative sexual attitudes; for men, intrinsic religiosity predicted sexual attitude conservatism but spirituality predicted attitudinal liberalism. For women, both religious group and religiosity domains were significant predictors of frequency of sexual fantasies while, for men, only religiosity domains were significant predictors. These results indicate that individual differences in religiosity domains were better predictors of sexual attitudes and fantasy than religious group and that these associations are moderated by gender. PMID- 20364305 TI - The benefits and drawbacks of gender typing: how different dimensions are related to psychological adjustment. AB - The benefits versus costs of gender typing are not clear: Is adjustment optimal when people identify and act in strongly gendered ways or when they embrace characteristics of both sexes? Previous findings are inconsistent, in part because they are derived from different conceptualizations of gender typing. A comprehensive understanding of the mental health consequences of gender typing requires recognition of the multidimensionality of gender typing and simultaneous consideration of these dimensions. On the basis of previous work on individual measures, we hypothesized that adjustment would be differentially associated with different aspects of gender typing: positively with sex-congruent gender identity and male-typed personality traits, negatively with rigid gender attitudes, and minimally with female-typed personality traits and gender-typed activity interests. Structural equation models were used to enable testing of all associations simultaneously. Results from a sample of 401 undergraduate students supported our hypotheses. For both women and men, adjustment was positively associated with gender-congruent identity, instrumentality, and flexible gender attitudes, and minimally related to activity interests and expressivity. These findings clarify the mental health benefits and costs of gender typing and highlight the multidimensionality of gender typing. PMID- 20364306 TI - Sexual coercion victimization and perpetration in heterosexual couples: a dyadic investigation. AB - Sexual coercion (SC), or making another person engage in sexual activity despite his or her unwillingness to do so, has been shown to have negative consequences for victims, namely depression, anxiety, low self-esteem, and a negative view of one's sexual self. The goals of the present study were to investigate the rate of SC victimization and perpetration, inter-partner agreement concerning its occurrence, in addition to its degree of reciprocity within a sample of 222 heterosexual couples. SC within previous romantic relationships was also examined. Results showed that less than 30% of couples agreed on the occurrence of sexual coercion within their ongoing relationship. Moreover, dyadic responses rather than individual responses provided a more accurate estimation of the frequency of SC. Over one in two couples reported experiencing some SC. More specifically, 45% of couples reported female victimization, 30% reported male victimization, and 20% reported reciprocal SC. Conversely, both men and women reported more SC victimization within previous relationships than in their current one. Findings suggest that SC is a common, pervasive problem within couples and that it is underreported by both victims and perpetrators, regardless of gender. Consequently, more systematic research, prevention and intervention efforts are warranted. PMID- 20364307 TI - The influence of forgiveness and apology on cardiovascular reactivity and recovery in response to mental stress. AB - To investigate the relation between forgiveness and apology as they relate to cardiovascular reactivity and recovery, 29 men and 50 women were exposed to an interpersonal transgression (i.e., verbal harassment) while performing a serial subtraction task. Participants were categorized into high and low forgiveness groups based on scores on the forgiving personality scale. Following the task, approximately half of the participants received an apology from the experimenter for his/her comments during the task. Although no group differences in cardiovascular reactivity were observed during the serial subtraction task, persons high in forgiveness displayed more rapid diastolic and mean arterial blood pressure recovery than persons low in forgiveness. In response to the apology, participants displayed greater high frequency heart rate variability recovery compared to those who did not receive an apology. A significant apology x sex interaction was observed for diastolic blood pressure and mean arterial blood pressure. Women who received an apology exhibited faster recovery from the transgression than women who did not receive an apology. In contrast, men who received an apology exhibited delayed recovery from the transgression compared to men who did not receive an apology. These results indicate that there are potentially healthful benefits to forgiveness and apology, but the relation is influenced by situation and by sex. PMID- 20364308 TI - Involvement of MyoD and c-myb in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene. AB - BRCA1 is closely related to the pathogenesis of breast cancer, BRCA1 mRNA is reduced in sporadic breast cancer cells despite the lack of mutations. In the present report, we find that MyoD expression and BRCA1 expression is correlated in sporadic breast tumors, overexpression of MyoD and c-myb stimulates BRCA1 expression, knockdown of MyoD and c-myb attenuates BRCA1 expression and attenuates the ability of BRCA1 to protect cells against hydrogen peroxide. MyoD and c-myb interact with p300 and PCAF, forming activating transcriptional complexes which bind to E-box and c-myb sites on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Regulation of BRCA1 expression by MyoD and c-myb complexes may be part of an integral signaling pathway that determines and explains breast cancer susceptibility. Detection expression status of the various proteins in these complexes may predispose to the onset of sporadic breast cancer. PMID- 20364310 TI - Fluorine contamination in groundwater: a major challenge. AB - Fluoride in high concentration in groundwater has been reported from many parts of India. However, a systematic study is required to understand the behavior of fluoride in natural water in terms of local hydrogeological setting, climatic conditions, and agricultural practices. The present study is an attempt to assess hydrogeochemistry of groundwater in parts of Palar river basin pertaining to Kancheepuram district Tamil Nadu to understand the fluoride abundance in groundwater and to deduce the chemical parameters responsible for the dissolution activity of fluoride. The study area is geologically occupied by partly sedimentary and partly crystalline formations. A total of 50 dug cum borewell water samples, representing an area of 2,628.92 km2. The results of the chemical analyses in September 2009 show fluoride abundance in the range of 1 to 3.24 mg/l with 86% of the samples in excess of the permissible limit of 1.5 mg/l. Presence of fluoride-bearing minerals in the host rock, chemical properties like decomposition, dissociation, and dissolution, and their interaction with water are considered to be the main causes for fluoride in groundwater. Chemical weathering with relatively high alkalinity favors high concentration of fluoride in groundwater. Villagers who consume nonpotable high fluoride water may suffer from yellow, cracked teeth; joint pains; and crippled limbs and also age rapidly. PMID- 20364309 TI - Human epidermal growth factor receptor 2 expression in early breast cancer patients: a Swiss cost-effectiveness analysis of different predictive assay strategies. AB - Trastuzumab has conferred significant clinical benefits in HER-2-positive breast carcinomas. HER-2 status is determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridisation (FISH), but appropriate assessment of HER2 status remains subject to considerable debate. Data on the health economic impact of HER-2 test strategies are limited. A life-long Markov state transition model was used to assess costs and effectiveness of HER-2 assay strategies (based on IHC, FISH, both combined or FISH confirmation of IHC2+) for a hypothetical cohort of early breast cancer patients from the perspective of the Swiss health system. We compared clinically relevant strategies of predictive testing and subsequent trastuzumab treatment of HER-2-positive patients only. FISH testing was the most cost-effective strategy with an incremental cost-effectiveness ratio of ?12,245 per additional quality-adjusted life-year (QALY) gained, compared to no trastuzumab treatment. The next best strategy was parallel IHC and FISH, with costs of ?400,154/QALY gained compared to FISH alone. FISH as primary HER-2 testing modality remained the preferred option in deterministic and probabilistic sensitivity analysis. Predictive testing to identify adjuvant breast cancer patients who benefit from trastuzumab treatment is a clinical and economic necessity. Our model identifies FISH as the most cost-effective approach. PMID- 20364311 TI - Groundwater modeling of Saq Aquifer Buraydah Al Qassim for better water management strategies. AB - Saudi Arabia is an arid country. It has limited water supplies. About 80-90% of water supplies come from groundwater, which is depleting day by day. It needs appropriate management. This paper has investigated groundwater modeling of Saq Aquifer in Buraydah Al Qassim to estimate the impact of its excessive use on depletion of Saq Aquifer. MODFLOW model has been used in this study. Data regarding the aquifer parameters was measured by pumping tests. Groundwater levels and discharge of wells in the area for the year 2008 and previous record of year 1999 have been collected from Municipal Authority of Buraydah. Location of wells was determined by Garmin. The model has been run for different sets of pumping rates to recommend an optimal use of groundwater resources and get prolonged life of aquifer. Simulations have been made for a long future period of 27 years (2008-2035). Model results concluded that pumping from the Saq Aquifer in Buraydah area will result into significant cones of depression if the existing excessive pumping rates prevail. A drawdown up to 28 m was encountered for model run for 27 years for existing rates of pumping. Aquifer withdrawals and drawdowns will be optimal with the conservation alternative. The management scheme has been recommended to be adopted for the future protection of groundwater resources in Kingdom of Saudi Arabia. PMID- 20364312 TI - Effect of land use land cover change on soil erosion potential in an agricultural watershed. AB - Universal soil loss equation (USLE) was used in conjunction with a geographic information system to determine the influence of land use and land cover change (LUCC) on soil erosion potential of a reservoir catchment during the period 1989 to 2004. Results showed that the mean soil erosion potential of the watershed was increased slightly from 12.11 t ha(-1) year(-1) in the year 1989 to 13.21 t ha( 1) year(-1) in the year 2004. Spatial analysis revealed that the disappearance of forest patches from relatively flat areas, increased in wasteland in steep slope, and intensification of cultivation practice in relatively more erosion-prone soil were the main factors contributing toward the increased soil erosion potential of the watershed during the study period. Results indicated that transition of other land use land cover (LUC) categories to cropland was the most detrimental to watershed in terms of soil loss while forest acted as the most effective barrier to soil loss. A p value of 0.5503 obtained for two-tailed paired t test between the mean erosion potential of microwatersheds in 1989 and 2004 also indicated towards a moderate change in soil erosion potential of the watershed over the studied period. This study revealed that the spatial location of LUC parcels with respect to terrain and associated soil properties should be an important consideration in soil erosion assessment process. PMID- 20364313 TI - Groundwater resource assessment, categories, and typologies: case study, Andhra Pradesh, India. AB - In India, groundwater assessment units are classified as overexploited areas, critical areas, semi-critical, or safe areas based on the stage of groundwater development and long-term water level trends. Intuitively, in the safe units, wells are expected to function and have good yields. Besides, in the safe units, new wells are expected to be successful. Conversely, the expectation of a successful well or wells with good yields is much lesser in the overexploited units. However, when these expectations are not met in the field, doubts are raised about the quality of assessment and its usefulness, and there is outright distrust on the agencies assessing groundwater resource by the common man as well as on the planners, administrators, and the politicians. Therefore, there is a need to present the results in a way that does not create confusion. One of the methods is to combine the assessment results with aquifer characters using geographic information system (GIS); when this is done, a whole set of newer classes emerge, which can be mapped. These classes are termed as groundwater typologies in this study. Each typology has some characteristics or traits in common, which include basic aquifer character as well as the stage of groundwater development. Thus, a class may be safe, but if the aquifer is poor, then it is separated from a class that is safe and where the aquifer is good and so on. In Andhra Pradesh, which is taken as the case study for this purpose, eight main typologies emerged, and two of these main typologies were further divided into four subtypologies each. This new way of understanding the pattern of groundwater abstraction (using GIS) has a better visual impact. Groundwater typologies are found to be much more rational and useful in developing management strategies, rather than simple listing as overexploited areas, critical areas, semi-critical areas, and safe areas as is commonly done. The typologies so delineated indicate on the map (or table) that balanced usable groundwater is in between 5 and 6 bcm/a as against the estimated balance of 20.5 bcm/a, and it is largely in poor hard rock type of aquifers, which occupy about a third of the area of the state. PMID- 20364314 TI - Co-assessment of biomass and soil organic carbon stocks in a future reservoir area located in Southeast Asia. AB - An assessment of the organic carbon stock present in living or dead vegetation and in the soil on the 450 km2 of the future Nam Theun 2 hydroelectric reservoir in Lao People's Democratic Republic was made. Nine land cover types were defined on the studied area: dense, medium, light, degraded, and riparian forests; agricultural soil; swamps; water; and others (roads, construction sites, and so on). Their geographical distribution was assessed by remote sensing using two 2008 SPOT 5 images. The area is mainly covered by dense and light forests (59%), while agricultural soil and swamps account for 11% and 2%, respectively. For each of these cover types, except water, organic carbon density was measured in the five pools defined by the Intergovernmental Panel on Climate Change: aboveground biomass, litter, deadwood, belowground biomass, and soil organic carbon. The area weighted mean carbon densities for these pools were estimated at 45.4, 2.0, 2.2, 3.4, and 62.2 tC/ha, respectively, i.e., a total of about 115+/-15 tC/ha for a soil thickness of 30 cm, corresponding to a total flooded organic carbon stock of 5.1+/-0.7 MtC. This value is much lower than the carbon density for some South American reservoirs for example where total organic carbon stocks range from 251 to 326 tC/ha. It can be mainly explained by (1) the higher biomass density of South American tropical primary rainforest than of forests in this study and (2) the high proportion of areas with low carbon density, such as agricultural or slash-and-burn zones, in the studied area. PMID- 20364315 TI - Carbon fixation efficiency of plants influenced by sulfur dioxide. AB - In the land ecosystem, the forest can absorb the carbon dioxide (CO2) in the atmosphere and turn the CO2 into organic carbon to store it in the plant body. About 2*10(11) tons of CO2 changes through photosynthesis into organic matter by plant annually. In this research, ten kinds of woody plants were selected for assessing the carbon fixation ability influenced by sulfur dioxide (SO2). The tested trees were put into a fumigation chamber for 210 days in a 40-ppb SO2 environment. The results of this study showed that there was no clear symptom of tested trees under a 40-ppb SO2 environment. The tested trees could tolerate this polluted environment, but it will impact their CO2 absorption ability. The carbon fixation ability will reduce as the polluted period lengthens. The carbon fixation potential of tested trees ranged from 2.1 to 15.5 g.CO2/m2.d with an average of 7.7 g.CO2/m2.d. The changes in CO2 absorption volume for Messerschmidia argentea were more stable during the fumigation period with a variation of 102%. Among the tested trees, Diospyros morrisiana had the best carbon fixation potential of 9.19 g.CO2/m2.d and M. argentea had the least with 2.54 g.CO2/m2.d. PMID- 20364316 TI - Monitoring seasonal bat activity on a coastal barrier island in Maryland, USA. AB - Research on effects of wind turbines on bats has increased dramatically in recent years because of significant numbers of bats killed by rotating wind turbine blades. Whereas most research has focused on the Midwest and inland portions of eastern North America, bat activity and migration on the Atlantic Coast has largely been unexamined. We used three long-term acoustic monitoring stations to determine seasonal bat activity patterns on the Assateague Island National Seashore, a barrier island off the coast of Maryland, from 2005 to 2006. We recorded five species, including eastern red bats (Lasiurus borealis), big brown bats (Eptesicus fuscus), hoary bats (Lasiurus cinereus), tri-colored bats (Perimyotis subflavus), and silver-haired bats (Lasionycteris noctivagans). Seasonal bat activity (number of bat passes recorded) followed a cosine function and gradually increased beginning in April, peaked in August, and declined gradually until cessation in December. Based on autoregressive models, inter night bat activity was autocorrelated for lags of seven nights or fewer but varied among acoustic monitoring stations. Higher nightly temperatures and lower wind speeds positively affected bat activity. When autoregressive model predictions were fitted to the observed nightly bat pass totals, model residuals>2 standard deviations from the mean existed only during migration periods, indicating that periodic increases in bat activity could not be accounted for by seasonal trends and weather variables alone. Rather, the additional bat passes were attributable to migrating bats. We conclude that bats, specifically eastern red, hoary, and silver-haired bats, use this barrier island during migration and that this phenomenon may have implications for the development of near and offshore wind energy. PMID- 20364317 TI - Deciphering groundwater potential zones in hard rock terrain using geospatial technology. AB - Remote sensing and geographical information system (GIS) has become one of the leading tools in the field of groundwater research, which helps in assessing, monitoring, and conserving groundwater resources. This paper mainly deals with the integrated approach of remote sensing and GIS to delineate groundwater potential zones in hard rock terrain. Digitized vector maps pertaining to chosen parameters, viz. geomorphology, geology, land use/land cover, lineament, relief, and drainage, were converted to raster data using 23 m*23 m grid cell size. Moreover, curvature of the study area was also considered while manipulating the spatial data. The raster maps of these parameters were assigned to their respective theme weight and class weights. The individual theme weight was multiplied by its respective class weight and then all the raster thematic layers were aggregated in a linear combination equation in Arc Map GIS Raster Calculator module. Moreover, the weighted layers were statistically modeled to get the areal extent of groundwater prospects with respect to each thematic layer. The final result depicts the favorable prospective zones in the study area and can be helpful in better planning and management of groundwater resources especially in hard rock terrains. PMID- 20364319 TI - Aging and heart failure: changing demographics and implications for therapy in the elderly. AB - The elderly population (age > or =65) is increasing and with it morbidity, hospitalizations, costs and mortality due to heart failure (HF). HF is a progressive disorder that is superimposed on an on-going aging process. The two broad categories of HF, HF with left ventricular (LV) systolic dysfunction or low ejection fraction (HF/low-EF) and HF with preserved ejection fraction (HF/PEF) are equally prevalent in the elderly. Trials of therapy for HF/low-EF in primarily non-elderly patients showed mortality benefit in elderly patients. In contrast, trials for HF/PEF have not shown mortality benefit in elderly or non elderly patients. HF pharmacotherapy in the elderly is challenging and needs to be individualized and consider several aging-related changes. More research into the biology of aging and more clinical trials in elderly patients are needed to improve morbidity and mortality in elderly HF patients. PMID- 20364318 TI - Control of autocrine and paracrine myocardial signals: an emerging therapeutic strategy in heart failure. AB - A growing body of evidence supports the hypothesis that autocrine and paracrine mechanisms, mediated by factors released by the resident cardiac cells, could play an essential role in the reparative process of the failing heart. Such signals may influence the function of cardiac stem cells via several mechanisms, among which the most extensively studied are cardiomyocyte survival and angiogenesis. Moreover, besides promoting cytoprotection and angiogenesis, paracrine factors released by resident cardiac cells may alter cardiac metabolism and extracellular matrix turnover, resulting in more favorable post-injury remodeling. It is reasonable to believe that critical intracellular signals are activated and modulated in a temporal and spatial manner exerting different effects, overall depending on the microenvironment changes present in the failing myocardium. The recent demonstration that chemically, mechanically or genetically activated cardiac cells may release peptides to protect tissue against ischemic injury provides a potential route to achieve the delivery of specific proteins produced by these cells for innovative pharmacological regenerative therapy of the heart. It is important to keep in mind that therapies currently used to treat heart failure (HF) and leading to improvement of cardiac function fail to induce tissue repair/regeneration. As a matter of facts, if specific autocrine/paracrine cell-derived factors that improve cardiac function will be identified, pharmacological-based therapy might be more easily translated into clinical benefits than cell-based therapy. This review will focus on the recent development of potential pharmacologic targets to promote and drive at molecular level the cardiac repair/regeneration in HF. PMID- 20364320 TI - Induction of vascular endothelial growth factor and matrix metalloproteinase-9 via CD47 signaling in neurovascular cells. AB - Neurovascular injury comprises a wide spectrum of pathophysiology that underlies the progression of brain injury after cerebral ischemia. Recently, it has been shown that activation of the integrin-associated protein CD47 mediates the development of blood-brain barrier injury and edema after cerebral ischemia. However, the mechanisms that mediate these complex neurovascular effects of CD47 remain to be elucidated. Here, we compare the effects of CD47 signaling in brain endothelial cells, astrocytes, and pericytes. Exposure to 4N1 K, a specific CD47 activating peptide derived from the major CD47 ligand thrombospondin-1, upregulated two major neurovascular mediators, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), in brain endothelial cells and astrocytes. No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke. PMID- 20364321 TI - Bayesian phase II adaptive randomization by jointly modeling time-to-event efficacy and binary toxicity. AB - In oncology, toxicity is typically observable shortly after a chemotherapy treatment, whereas efficacy, often characterized by tumor shrinkage, is observable after a relatively long period of time. In a phase II clinical trial design, we propose a Bayesian adaptive randomization procedure that accounts for both efficacy and toxicity outcomes. We model efficacy as a time-to-event endpoint and toxicity as a binary endpoint, sharing common random effects in order to induce dependence between the bivariate outcomes. More generally, we allow the randomization probability to depend on patients' specific covariates, such as prognostic factors. Early stopping boundaries are constructed for toxicity and futility, and a superior treatment arm is recommended at the end of the trial. Following the setup of a recent renal cancer clinical trial at M. D. Anderson Cancer Center, we conduct extensive simulation studies under various scenarios to investigate the performance of the proposed method, and compare it with available Bayesian adaptive randomization procedures. PMID- 20364322 TI - Glomerular filtration rate (GFR) estimated from serum creatinine predicts total (urine and peritoneal) creatinine clearance in patients on peritoneal dialysis. AB - OBJECTIVES: The aim of this study was to examine the accuracy of the Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft and Gault formula (CCrCG) in predicting total creatinine clearance achieved by residual renal function plus peritoneal dialysis in patients on chronic peritoneal dialysis. METHODS: Total creatinine clearance was defined as peritoneal creatinine clearance (PCcr) plus the average of urine urea and creatinine clearances (cGFR). Correlation analysis and Bland-Altman plot were used to establish the degree of correlation and agreement between the estimations of creatinine clearance achieved by PCcr and the average of cGFR and estimated creatinine clearance based on serum creatinine by using either MDRD equation or the Cockcroft and Gault formula. RESULTS: In one hundred fifty-six measurements, mean clearances by [cGFR + PCcr], CCrCG and MDRD were: 7.9 +/- 3.1, 10.6 +/- 5.2 and 8.5 +/- 4.9 ml/min/1.73 m(2), respectively. There was a good correlation between [cGFR + PCcr] and MDRD (r = 0.776, P < 0.05) and [cGFR + PCcr] and CCrCG (r = 0.735, P < 0.05). The mean MDRD was not significantly different from the mean clearance by [cGFR + PCcr] (difference 0.4 +/- 2.9 ml/min/1.73 m(2), agreement limit -5.4-6.3 ml/min/1.73 m(2)). The CCrCG formula gave a larger difference from the mean [cGFR + PCcr] (2.8 +/- 10.5 ml/min/1.73 m(2)) and a much wider agreement limit (-3.7 9.3 ml/min/1.73 m(2)). In male patients, MDRD formula provided an estimate of clearance that was similar to the mean [cGFR + PCcr] (7.9 +/- 3.8 ml/min/1.73 m(2) vs. 8.2 +/- 3.2 ml/min/1.73 m(2), respectively; difference 0.10 +/- 1.9 ml/min/1.73 m(2), limits of agreement -3.9-3.7 ml/min/1.73 m(2)). By contrast, in female patients, the MDRD equation significantly overestimated the clearance (difference between mean estimated and mean measured clearance 1.4 +/- 4.1 ml/min/1.73 m(2), limits of agreement -6.6-9.5 ml/min/1.73 m(2) P < 0.05). In conclusion, the GFR estimated by MDRD formula is similar to [cGFR + PCcr] especially in males. GFR by the CCrCG formula tended to overestimate the highest values of [cGFR + PCcr]. PMID- 20364323 TI - The clinical applicability of the Self-Appraisal of Illness Questionnaire (SAIQ) to chronic schizophrenic patients in Taiwan. AB - Over the last decade, several self-report instruments to assess insight of illness from schizophrenic patients' perspectives have been administered. The main purpose of this study was to ascertain the reliability and validity of the Taiwanese version of the Self-Appraisal of Illness Questionnaire (SAIQ) in a chronic schizophrenic sample in Taiwan. This scale is a self-administered instrument designed to evaluate attitudes toward mental illness among patients receiving treatment. In the current cross-sectional study, 104 patients who met DSM-IV criteria for schizophrenic disorders were recruited and independently interviewed. The psychometric properties of the translated SAIQ were determined, including internal consistency, test-retest reliability, and construct validity. In addition, we analyzed psychosocial and clinical characteristics as correlates of the Taiwanese version of the SAIQ. Overall, the Taiwanese version of the SAIQ was found to be internally consistent and reliable over time. This translated scale comprised a three-factor solution with factors corresponding to worry, the need for treatment, and presence/outcome subscales. The results also indicated that the three subscales and its total score were significantly associated with both the research-rated insight scale and psychopathology and mood state. This culture-specific study shows that the Taiwanese version of the SAIQ is a simple and reliable scale for use. PMID- 20364324 TI - MR image-based geometric and hemodynamic investigation of the right coronary artery with dynamic vessel motion. AB - The aim of this study was to develop a fully subject-specific model of the right coronary artery (RCA), including dynamic vessel motion, for computational analysis to assess the effects of cardiac-induced motion on hemodynamics and resulting wall shear stress (WSS). Vascular geometries were acquired in the right coronary artery (RCA) of a healthy volunteer using a navigator-gated interleaved spiral sequence at 14 time points during the cardiac cycle. A high temporal resolution velocity waveform was also acquired in the proximal region. Cardiac induced dynamic vessel motion was calculated by interpolating the geometries with an active contour model and a computational fluid dynamic (CFD) simulation with fully subject-specific information was carried out using this model. The results showed the expected variation of vessel radius and curvature throughout the cardiac cycle, and also revealed that dynamic motion of the right coronary artery consequent to cardiac motion had significant effects on instantaneous WSS and oscillatory shear index. Subject-specific MRI-based CFD is feasible and, if scan duration could be shortened, this method may have potential as a non-invasive tool to investigate the physiological and pathological role of hemodynamics in human coronary arteries. PMID- 20364325 TI - Heterologous expression of ApGSMT2 and ApDMT2 genes from Aphanothece halophytica enhanced drought tolerance in transgenic tobacco. AB - The glycine-methylation biosynthetic pathway of glycinebetaine (GB) has been investigated, but only a few studies on GB accumulation in transgenic higher plants have utilized this pathway. In this study, two methyltransferase genes named ApGSMT2 and ApDMT2, encoding proteins catalyzing GB biosynthesis from glycine, were cloned from a relative strain of Aphanothece halophytica. The potential roles of ApGSMT2 and ApDMT2 in GB synthesis were first examined in transgenic Escherichia coli, which had increased levels of GB and improved salt tolerance. Then ApGSMT2 and ApDMT2 were transferred into tobacco. Compared with transgenic tobacco expressing betA, transgenic tobacco co-expressing ApGSMT2 and ApDMT2 accumulated more GB and exhibited enhanced drought resistance with better germination performance, higher relative water content, less cell membrane damage and better photosynthetic capacity under drought stress. We concluded that the ApGSMT2 and ApDMT2 genes cloned in this study will be very useful for engineering GB-accumulating transgenic plants with enhanced drought resistance. PMID- 20364326 TI - The complete mitochondrial genome of Thrinchus schrenkii (Orthoptera: Caelifera, Acridoidea, Pamphagidae). AB - Complete nucleotide sequences of mitochondrial genome (mitogenome) of Thrinchus schrenkii (Orthoptera: Acridoidea: Pamphagidae) were determined. It is 15672 bp in length and contains 71.2% A+T. All T. schrenkii protein-coding sequences except for the cytochrome oxidase subunit I (COI) start with a typical ATN codon. Instead, CCG, which is a rare but possible initiation codon, is located at the initiation context of COI. The usual termination codons (TAA and TAG) were found from 12 PCGs. However, the ND5 had incomplete termination codon (T). All tRNA genes could be folded into the typical cloverleaf secondary structure, excluding tRNASer(AGN) which forms another structure according to the Steinberg-Cedergren tertiary structure. The sizes of the large and small ribosomal RNA genes are 1319 and 848 bp, respectively. The A+T content of the A+T-rich region is 78.7%, which is the lowest among the known mitogenome of Acridoidea. PMID- 20364327 TI - SIGIRR inhibits toll-like receptor 4, 5, 9-mediated immune responses in human airway epithelial cells. AB - Human airway epithelial cells (HAEC) may contribute to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) through toll-like receptors (TLRs) mediated molecular mechanisms. TLRs exist on the surface of HAEC where binding to their cognate ligands initiates airway inflammation. Single immunoglobulin interleukin-1 receptor-related protein (SIGIRR) is a member of the toll interleukin-1 receptor (TIR) family that can negatively modulate the immune response. We carried out studies to characterize SIGIRR modulation of TLR mediated immune response in HAEC and to define its mechanisms of action. Following treatment with various concentrations of LPS, flagellin and CpG DNA, the levels of cognate TLRs 4, 5, and 9 were measured in the supernatants of HAEC over-expressing the SIGIRR molecule. Moreover, the interaction of the TLR adaptor myeloid differentiation factor 88 (MyD88) with SIGIRR in response to LPS-, flagellin- and CpG DNA-stimulation was examined by co-immunoprecipitation. The findings from this study revealed that overexpression of SIGIRR in HAEC stimulated by LPS, flagellin or CpG DNA resulted in attenuated production of the inflammatory mediators IL-6 and TNF-alpha. This attenuation was not the result of decreased expression of TLR4, 5 or 9, but rather a sequestration of MyD88 to the TLRs. In conclusion, SIGIRR can inhibit TLR4, 5, and 9-mediated immune responses in HAEC and may be a valuable therapeutic target for the prevention of ALI/ARDS. PMID- 20364328 TI - Silencing CX3CR1 production modulates the interaction between dendritic and endothelial cells. AB - CX3CR1, an important chemokine receptor in dendritic cells (DCs), is linked to the progression of atherosclerotic plaques. However, the mechanism(s) determining the role of CX3CR1 in atherosclerosis have not been clearly elucidated. In this study, we developed DCs from monocytes of Sprague-Dawley (SD) rats in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant human interleukin-4 (IL-4). The presence of recombinant human TNF-alpha and LPS forced the cells to mature. When compared to immature DCs, flow cytometry (FACS) analysis revealed that mature DCs display a sustained increase in the levels of CD11c, CD86, and CD80 expression. The expression of Fractalkine (FKN) in endothelial cells (ECs) contributes to the maturation of DCs and expression of CX3CR1. We revealed that mRNA expression levels of CX3CR1 in mature DCs are significantly higher than those of immature DCs (P<0.001). Transfection of DCs with siRNA specific for the CX3CR1 gene resulted in potent suppression of gene expression and inhibition of interactions between DCs and ECs. Based on these data, we hypothesized that CX3CR1 contributes to the DC-EC interaction. CX3CR1 may serve as a new target molecule for increasing therapeutic interactions in atherosclerosis. PMID- 20364329 TI - Characterization of the GHR gene genetic variation in Chinese indigenous goat breeds. AB - The aim of the present work was to investigate single nucleotide polymorphism (SNP) of growth hormone receptor (GHR) gene exon 10, characterize the genetic variation in three Chinese indigenous goat breeds, and search for its potential association with cashmere traits. In this study, a polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) protocol has been developed for rapid genotyping of the GHR gene in goats. One hundred seventy-eight goats from Liaoning Cashmere (96), Inner Mongolia White Cashmere (40), and Chengdu Grey (42) breeds in China were genotyped at GHR locus using the protocol developed. In all goat breeds investigated, a SNP in exon 10 of GHR gene has been identified by analyzing genomic DNA. The polymorphism consists of a single nucleotide substitution A -> G, resulting in two alleles named, respectively, A and G based on the nucleotide at the position. The allele A was found to be more common in the animals investigated, and seems to be more consistent with cattle and zebu at this polymorphic site found in goats. The Hardy-Weinberg equilibrium of genotype distributions of GHR locus was verified in Liaoning Cashmere, and Inner Mongolia White Cashmere breeds. According to the classification of polymorphism information content (PIC), Chengdu Grey was less polymorphic than Liaoning Cashmere and Inner Mongolia White Cashmere breeds at this locus. The phylogenetic tree of different species based on the nucleotide sequences of GHR gene exon 10 is generally in agreement with the known species relationship. No significant association was found between the polymorphism revealed and the cashmere traits analyzed in present work. PMID- 20364330 TI - Glutamate receptors and signal transduction in learning and memory. AB - The plasticity of the central nervous system helps form the basis for the neurobiology of learning and memory. Long-term potentiation (LTP) is the main form of synaptic plasticity, reflecting the activity level of the synaptic information storage process, and provides a good model to study the underlying mechanisms of learning and memory. The glutamate receptor-mediated signal pathway plays a key role in the induction and maintenance of LTP, and hence the regulation of learning and memory. The progress in the understanding of the glutamate receptors and related signal transduction systems in learning and memory research are reviewed in this article. PMID- 20364331 TI - The association of CLOCK gene T3111C polymorphism and hPER3 gene 54-nucleotide repeat polymorphism with Chinese Han people schizophrenics. AB - Many reports have shown that the biologic rhythm could be altered due to mutations of circadian gene hClock or hPeriod, and the mutations of circadian genes have some relationship with psychosis according to recent studies. A preliminary study has been conducted to examine wether the T3111C single nucleotide polymorphism of the hClock gene or the length polymorphism of the hPer3 gene is associated with the development of schizophrenia. The samples from schizophrenics (n=148, male: 57.4%, female: 42.6%) and normal controls (n=199, male: 59.3%, female: 40.7%) were examined. Allele frequencies of T3111C SNP of hClock were significantly different between schizophrenics and controls (chi2=19.738, P<0.05). Schizophrenics had a significantly higher frequency of the C allele compared with controls (OR=2.613, 95% CI=1.693-4.034). On the other hand, there is no significant difference of allele frequencies of 18 exon of hper3 between schizophrenics and controls (chi2=0.192, P>0.05). Our results suggest that the T3111C (RS1801260) polymorphism of hClock gene is associated with schizophrenia, but it seems that the length polymorphism of 18 exon of hPer3 may not be associated with schizophrenia. It is important to address of the relationship between circadian gene polymorphisms and dopamine functions in further study. PMID- 20364332 TI - Development and psychometric evaluation of the Endometriosis Treatment Satisfaction Questionnaire. AB - PURPOSE: To develop and psychometrically evaluate the Endometriosis Treatment Satisfaction Questionnaire, a patient-reported assessment of satisfaction with endometriosis treatment. METHODS: The Endometriosis Treatment Satisfaction Questionnaire was developed based on the results of five focus groups and three iterative sets of cognitive interviews along with expert opinion and a review of the literature. The psychometric properties were assessed using data collected during a multicenter, randomized, proof-of-concept trial. The development and validation processes followed the guidance recommended by the United States FDA for patient-reported outcome instruments. RESULTS: The Endometriosis Treatment Satisfaction Questionnaire's reliability, validity, and utility as a measure of patient satisfaction with their endometriosis treatment were supported. The results of the item-level analyses showed no evidence of distributional anomalies or response scale biases. The Endometriosis Treatment Satisfaction Questionnaire is unidimensional, has excellent internal consistency reliability, and discriminates well between known groups. Scores correlated well with other patient-reported outcome measures of endometriosis without being redundant. CONCLUSIONS: The Endometriosis Treatment Satisfaction Questionnaire has utility for assessing patient satisfaction with endometriosis treatment and may be useful in clinical trials that are assessing new treatments for endometriosis, especially when deciding between competing treatments or regimens that are found to have similar tolerability and efficacy. PMID- 20364334 TI - Response for letter to editor (NECA-10-21[1]) on "the predictive value of serum semi-quantitative procalcitonin for neurological outcome after cardiac arrest: preliminary data". PMID- 20364333 TI - X-ray structure determination of the glycine cleavage system protein H of Mycobacterium tuberculosis using an inverse Compton synchrotron X-ray source. AB - Structural genomics discovery projects require ready access to both X-ray diffraction and NMR spectroscopy which support the collection of experimental data needed to solve large numbers of novel protein structures. The most productive X-ray crystal structure determination laboratories make extensive use of tunable synchrotron X-ray light to solve novel structures by anomalous diffraction methods. This requires that frozen cryo-protected crystals be shipped to large multi acre synchrotron facilities for data collection. In this paper we report on the development and use of the first laboratory-scale synchrotron light source capable of performing many of the state-of-the-art synchrotron applications in X-ray science. This Compact Light Source is a first-in-class device that uses inverse Compton scattering to generate X-rays of sufficient flux, tunable wavelength and beam size to allow high-resolution X-ray diffraction data collection from protein crystals. We report on benchmarking tests of X-ray diffraction data collection with hen egg white lysozyme, and the successful high resolution X-ray structure determination of the Glycine cleavage system protein H from Mycobacterium tuberculosis using diffraction data collected with the Compact Light Source X-ray beam. PMID- 20364335 TI - Expression of phosphatase of regenerating liver-3 in squamous cell carcinoma of the cervix. AB - To investigate the significance of PRL-3 expression in progression and metastasis of squamous cell carcinoma of the cervix (SCC). PRL-3 expression was detected by immunohistochemistry in 22 normal cervical epithelia, 30 moderate-severe dysplasia (CIN II-III) and 90 SCC cases. A total of 28 patients with SCC had lymph node metastasis, and PRL-3 expression of metastatic lymph node was detected. The association between PRL-3 expression and various clinical pathological variables in 90 patients with SCC was analyzed. Expression of PRL-3 in SCC was higher than that in normal and CINII-III, as well as higher in CINII III than in normal (P<0.05 in all instances). PRL-3 expression was significantly different between different tumor sizes, lymph-vascular space invasion status and lymph node metastasis status (P<0.05 in all instances). PRL-3 expression in lymph node metastasis was significantly higher than that in primary SCC (P=0.049). In lymph node metastasis, the frequency of staining in cytoplasm predominantly was higher than that in matched primary cancers (P=0.001). PRL-3 may be involved in carcinogenesis of cervix and lymph node metastases of SCC and serves as an unfavorable prognostic factor in patients with SCC. PRL-3 localization in plasma may be related with cancer progress and metastasis. PMID- 20364336 TI - Reproductive factors associated with breast cancer risk in northern Iran. AB - Breast cancer is a common malignancy for women in most parts of the world and the incidence in Iranian women is growing. The patients are relatively younger than their western counterparts. The aim of study was to investigate the roles of reproductive factors for breast cancer in Babol. In a case-control study in Babol, we recruited a total of 100 new patients with histologically confirmed breast cancer and 200 age-matched controls selected from outpatient clinics. Demographic and reproductive factors were ascertained by in-person interview using a constructed questionnaire. Several potential confounding factors were adjusted using multiple logistic model. The adjusted odds ratio showed that having higher age at first pregnancy and abortion were associated with increased breast cancer risk (the adjusted OR = 4.1, 95% CI: 1.3-13.2 and 2.93, 95% CI: 1.64-5.24, respectively). By increasing parity, the risk had reduced significantly; among women with parity >= 5, the adjusted OR was 0.09 (95% CI 0.01-0.7) compared with nulliparous women, and also for each additional parity, the risk reduced by 50% (OR = 0.50, 95% CI: 0.34-0.71). The duration of breast feeding was inversely associated with breast cancer risk, while after additional adjustment for parity, no longer the protective effect of breast feeding was observed. Nulliparity, late age at first birth and abortion were the most important reproductive factors associated with breast cancer risk; therefore, it is recommended to women with these risk factors to perform breast cancer screening tests earlier. PMID- 20364337 TI - Extraneural sclerosing perineurioma of the buccal mucosa: a case report and clinicopathologic review. AB - The perineurioma is an infrequently encountered benign peripheral nerve sheath tumor composed of a clonal proliferation of perineurial cells. Rare cases of perineurioma have been reported in the oral cavity. An extraneural sclerosing perineurioma arising in the buccal mucosa of a 17-year-old male is presented. Histopathologically, the tumor is composed of a well circumscribed nodular proliferation of spindle cells arranged in a storiform growth pattern, in some areas subtly arranged around vascular channels. The tumor cells reveal positive immunostaining for epithelial membrane antigen (EMA), collagen type IV and vimentin, and negative immunostaining for S-100 protein, consistent with a perineurial origin. To the best of our knowledge, this case represents the first report of an extraneural sclerosing perineurioma involving the oral cavity. PMID- 20364338 TI - Biographical Sketch: Baron Joseph Lister, FRCS, 1827-1912. AB - This biographical sketch on Baron Joseph Lister corresponds to the historic text, The Classic: On the Antiseptic Principle in the Practice of Surgery (1867), available at DOI 10.1007/s11999-010-1320-x . PMID- 20364340 TI - Temporal and spatial patterns of cortical activation during assisted lower limb movement. AB - Human gait is a complex process in the central nervous system that results from the integrity of various mechanisms, including different cortical and subcortical structures. In the present study, we investigated cortical activity during lower limb movement using EEG. Assisted by a dynamic tilt table, all subjects performed standardized stepping movements in an upright position. Source localization of the movement-related potential in relation to spontaneous EEG showed activity in brain regions classically associated with human gait such as the primary motor cortex, the premotor cortex, the supplementary motor cortex, the cingulate cortex, the primary somatosensory cortex and the somatosensory association cortex. Further, we observed a task-related power decrease in the alpha and beta frequency band at electrodes overlying the leg motor area. A temporal activation and deactivation of the involved brain regions as well as the chronological sequence of the movement-related potential could be mapped to specific phases of the gait-like leg movement. We showed that most cortical capacity is needed for changing the direction between the flexion and extension phase. An enhanced understanding of the human gait will provide a basis to improve applications in the field of neurorehabilitation and brain-computer interfaces. PMID- 20364339 TI - Staging in neuropsychiatry: a heuristic model for understanding, prevention and treatment. AB - The main mental disorders which develop and persist through adult life typically emerge during the critical developmental phase of adolescence and early adulthood, and are frequently associated with considerable associated distress and functional decline. Our current diagnostic system lacks validity and therapeutic utility, particularly for the early stages of these mental disorders, when symptoms are still evolving and may have not yet stabilised sufficiently to fit familiar or traditional syndromal criteria. Furthermore, there is often difficulty in distinguishing transient developmental or normative changes from the early symptoms of persistent and disabling mental illness. These factors point to the need for reform of our current diagnostic systems. The clinical staging model seeks to define the extent of progression of a disorder at a particular point in time and aims to differentiate early, milder clinical phenomena from those that accompany illness progression and chronicity. The staging framework allows clinicians to select treatments relevant to earlier stages of an illness, and to evaluate their effectiveness in preventing progression and producing remission or return to milder or earlier stages of disorder. For staging to be a valid approach, interventions in the early stages need to shown to be not only more effective but also safer than treatments delivered later in the course of illness. Staging may also allow a more efficient integration of our rapidly expanding knowledge of the biological, social and psychological vulnerability factors involved in development of mental illness into what may ultimately resemble a clinicopathological staging model. PMID- 20364341 TI - A canonical cation-pi interaction stabilizes the agonist conformation of estrogen like nuclear receptors. AB - Representative crystal structures of the ligand-binding domain for the majority of nuclear receptors are currently available. A systematic comparative analysis of these structures identified an energetically favorable cation-pi interaction that involves an amino acid located at the extreme C-terminal end and appears to form only in the agonist conformation of the estrogen receptor alpha, glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. It is postulated that this cation-pi interaction is used by members of the estrogen like subfamily to provide additional stabilization to the transcriptional active conformation upon ligand binding. PMID- 20364342 TI - Functional interactions among members of the meiotic initiation complex in fission yeast. AB - DNA double-strand breaks (DSBs) initiate meiotic recombination in Schizosaccharomyces pombe and in other organisms. The Rec12 protein catalyzes the formation of these DSBs in concert with a multitude of accessory proteins the role of which in this process remains to be discovered. In an all-to-all yeast two-hybrid matrix analysis, we discovered new interactions among putative members of the meiotic recombination initiation complex. We found that Rec7, an axial element associated protein with homologies to Saccharomyces cerevisiae Rec114, is interacting with Rec24. Rec7 and Rec24 also co-immunoprecipitate in S. pombe during meiosis. An amino acid change in a conserved, C-terminal phenylalanine in Rec7, F325A interrupts the interaction with Rec24. Moreover, rec7F325A shows a recombination deficiency comparable to rec7Delta. Another interaction was detected between Rec12 and Rec14, the orthologs of which in S. cerevisiae Spo11 and Ski8 interact accordingly. Amino acid changes Rec12Q308A and Rec12R309A disrupt the interaction with Rec14, like the according amino acid changes Spo11Q376A and Spo11RE377AA loose the interaction with Ski8. Both amino acid changes in Rec12 reveal a recombination deficient rec12 (-) phenotype. We propose that both Rec7-Rec24 and Rec12-Rec14 form subcomplexes of the meiotic recombination initiation complex. PMID- 20364343 TI - Enzyme activity in the aestivating green-striped burrowing frog (Cyclorana alboguttata). AB - Green-striped burrowing frogs (Cyclorana alboguttata) can depress their resting metabolism by more than 80% during aestivation. Previous studies have shown that this species is able to withstand long periods of immobilisation during aestivation while apparently maintaining whole muscle mass and contractile performance. The aim of this study was to determine the effect of prolonged aestivation on the levels of metabolic enzymes (CCO, LDH and CS) in functionally distinct skeletal muscles (cruralis, gastrocnemius, sartorius, iliofibularis and rectus abdominus) and liver of C. alboguttata. CS activity was significantly reduced in all tissues except for the cruralis, gastrocnemius and the liver. LDH activity was significantly reduced in the sartorius and rectus abdominus, but remained at control (active) levels in the other tissues. CCO activity was significantly reduced in the gastrocnemius and rectus abdominus, and unchanged in the remaining tissues. Muscle protein was significantly reduced in the sartorius and iliofibularis during aestivation, and unchanged in the remaining muscles. The results suggest that the energy pathways involved in the production and consumption of ATP are remodelled during prolonged aestivation but selective. Remodelling and subsequent down-regulation of metabolic activity seem to target the smaller non-jumping muscles, while the jumping muscles retain enzyme activities at control levels during aestivation. These results suggest a mechanism by which aestivating C. alboguttata are able to maintain metabolic depression while ensuring that the functional capacity of critical muscles is not compromised upon emergence from aestivation. PMID- 20364344 TI - Chronic fatigue syndrome: a hormonal origin? A rare case of dysmenorrhoea membranacea-alternative pathology. PMID- 20364345 TI - Age-independent first trimester screening for Down syndrome: analysis of three modified software programs with 6,508 pregnancies. AB - BACKGROUND: The conventional first trimester screening (FTS) method integrates maternal age into risk calculation. It was suggested that this concept increases the false-positive rate in older, and the false-negative rate in younger mothers. MATERIALS AND METHODS: Six thousand five hundred and eight combined FTS with known fetal outcome underwent regular risk calculation with the software programs Pia fetal database (PIA) (GE-ViewPoint, GE Medical Systems), prenatal risk calculation (PRC) (Version 1.0.61, gmt/nexus), and JOY (Version 2.1, PET software). The results were mathematically modified as if generated with age independent software (PIA(mod), PRC(mod), and JOY(mod)). RESULTS: 17 of 40 trisomy 21 cases were present in women younger than 35. A right shift in the mean maternal age of false-negative cases occurred in all programs (PIA: 30.00, PIA(mod): 32.00, PRC: 30.00, PRC(mod): 32.25, JOY: 30.00, JOY(mod): 34.50). The overall false-positive rate declined by -40.03% (PIA(mod)), -38.64% (PRC(mod)), and -37.50% (JOY(mod)) and in women over 35 (40) years by -72.37, -73.45, and 73.20% (-89.04, -90.33, and -90.56%), being then as high as in the other age groups. CONCLUSION: First trimester screening would become reasonable in women over 40 years. However, women over 35 would also be more often affected by false negative results. The implications of a concept adaptation should be analyzed in a large prospective study. PMID- 20364346 TI - The effects of methylprednisolone and halofuginone on preventing esophageal and hypopharyngeal fibrosis in delivered radiotherapy. AB - In this study, we assessed the effects of halofuginone and methylprednisolone on hypopharyngeal and esophageal stricture that can develop following radiation to the head and neck of rats. Rats were divided into four groups randomly and 18 Gy radiation was given to the head and neck regions of all rats except the control group. Group 1 (Control Group): No radiation or drugs were administered. Group 2 (Radiation Group): only radiation was applied without any drugs. Group 3 (Halofuginone Group): halofuginone 100 microg/kg per day was given intraperitoneally. Group 4 (Methylprednisolone Group): methylprednisolone 1 mg/kg per day was administered intramuscularly. In all groups, 90 days after application of radiation, sections of the proximal esophagus and hypopharynx were examined for fibrosis, fibroblast proliferation, vascularization, epithelial atypia, necrosis, polymorphonuclear leukocytes, mononuclear cells, and stenosis index by light microscope and the hydroxyproline levels were assessed biochemically. Fibrosis, epithelial atypia and hydroxyproline levels were found to be significantly higher in the radiation group compared to the control group (P < 0.05). We did not observe fibrosis in either the halofuginone or the control groups. Fibrosis was also significantly lower in the methylprednisolone group than the radiation group (P < 0.05). The differences of the stenosis index scores between the groups were not statistically significant (P < 0.05). Vascularization was similar in all groups. We think that especially halofuginone is a drug that can be used safely to prevent fibrosis due to radiotherapy, but further studies are needed. PMID- 20364347 TI - Enhanced inflammation with high carbohydrate intake during recovery from eccentric exercise. AB - Inflammation associated with adipose tissue is modulated by macronutrient availability. For example, glucose increases inflammation in obese but not lean individuals. Little is known about how macronutrient intake influences inflammation associated with muscle. The aim of this study was to determine the impact of macronutrient intake differences during recovery from eccentric exercise on the inflammatory response. The study was a cross-over design in which young men and women (n = 12) completed high and low carbohydrate (CHO) conditions. Both conditions consisted of six sets of ten maximal high-force eccentric contractions of the elbow flexors and extensors followed by a controlled diet for the first 8 h post-exercise. Glucose, insulin, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and C-reactive protein were measured from blood samples pre-exercise, 1.5, 4, 8, and 24 h post-exercise. Perceived muscle soreness, strength loss, and serum CK activity were measured through 120 h post-exercise. Perceived soreness was elevated (P < 0.001) at all time points post-exercise in both conditions and was higher (P < 0.05) in the high compared to the low CHO condition. IL-1beta increased (P = 0.05) 24 h post-exercise in the high compared to the low CHO condition. There was a trend (P = 0.06) for IL-6 to be elevated in the high compared to the low CHO condition. We conclude that inflammation induced by high-force eccentric exercise in skeletal muscle is greater when a high CHO compared to a low CHO diet is consumed during recovery. PMID- 20364348 TI - Heterogeneity of muscle deoxygenation kinetics during two bouts of repeated heavy exercises. AB - This study examines the effect of prior heavy exercise on the spatial distribution of muscle deoxygenation kinetics at the onset of heavy-intensity cycling exercise. Young untrained male adults (n = 16) performed two consecutive bouts of 6 min of high intensity cycle exercise separated by 6 min at 35 W. Muscle deoxygenation (HHb) was monitored continuously by near-infrared spectroscopy at eight sites in the quadriceps. Prior heavy exercise reduced the delay before the increase in HHb (9 +/- 2 vs. 5 +/- 2 s; P < 0.001). The standard deviation of TD HHb of the eight sites was decreased by the performance of prior exercise (1.1 +/- 0.5 vs. 0.8 +/- 0.4 s; P < 0.05). The transient decrease in HHb during the first 10 s of exercise was less during the second bout than during the first bout (0.6 +/- 0.6 vs. 0.3 +/- 0.3 A.U.; P < 0.01). The standard deviation of this decrease was also reduced by prior exercise (0.5 +/- 0.3 vs. 0.3 +/- 0.2 A.U.; P < 0.01). Lastly, prior exercise decreased significantly the standard deviation of the HHb rise during the time period corresponding to the pulmonary VO(2) slow component. These results indicate that prior heavy exercise reduced the spatial heterogeneity of muscle deoxygenation kinetics at the early onset of heavy exercise and during the development of the pulmonary VO(2) slow component. It indicates that the distribution of the VO(2)/O(2) delivery ratio within muscle was improved by the performance of a prior exercise. PMID- 20364349 TI - Impact of exercise training on oxidative stress in individuals with a spinal cord injury. AB - Individuals with a spinal cord injury (SCI) have an increased cardiovascular risk. We hypothesize that (anti)oxidative imbalance is associated with the increased cardiovascular risk in SCI, while exercise can reverse this status. The aim of the study is to compare baseline levels of oxidative stress and antioxidative capacity between individuals with SCI and able-bodied (AB) subjects, and to assess acute and long-term effects of functional electrical stimulation (FES) exercise on oxidative stress and antioxidative capacity in SCI. Venous blood was taken from subjects with an SCI (n = 9) and age- and gender matched AB subjects (n = 9) to examine oxidative stress through malondialdehyde (MDA) levels, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme levels represented anti-oxidative capacity. Subsequently, subjects with an SCI performed an 8-week FES exercise training period. Blood was taken before and after the first exercise bout and after the last FES session to examine the acute and chronic effect of FES exercise, respectively. Baseline levels of MDA, SOD and GPx were not different between individuals with SCI and AB subjects. SCI demonstrated a correlation between initial fitness level and MDA (R = -0.83, P = 0.05). MDA, SOD and GPx levels were neither altered by a single FES exercise bout nor by 8 weeks FES training. In conclusion, although individuals with an SCI demonstrate a preserved (anti)oxidative status, the correlation between fitness level and (anti)oxidative balance suggests that higher fitness levels are related to improved (anti)oxidative status in SCI. Nonetheless, the FES exercise stimulus was insufficient to acutely or chronically change (anti)oxidative status in individuals with an SCI. PMID- 20364350 TI - Quantitative analysis of directional strengths in jointly stationary linear multivariate processes. AB - Identification and analysis of directed influences in multivariate systems is an important problem in many scientific areas. Recent studies in neuroscience have provided measures to determine the network structure of the process and to quantify the total effect in terms of energy transfer. These measures are based on joint stationary representations of a multivariate process using vector auto regressive (VAR) models. A few important issues remain unaddressed though. The primary outcomes of this study are (i) a theoretical proof that the total coupling strength consists of three components, namely, the direct, indirect, and the interference produced by the direct and indirect effects, (ii) expressions to estimate/calculate these effects, and (iii) a result which shows that the well known directed measure for linear systems, partial directed coherence (PDC) only aids in structure determination but does not provide a normalized measure of the direct energy transfer. Simulation case studies are shown to illustrate the theoretical results. PMID- 20364351 TI - Evidences for insulator activity of the 5'UTR of the Drosophila melanogaster LTR retrotransposon ZAM. AB - Insulators or chromatin boundary are DNA elements that organize the genome into discrete regulatory domains by limiting the actions of enhancers and silencers through a "positional-blocking mechanism". The role of these sequences, both in modulation of the enhancers range of action (enhancer-promoter selectivity) and in the organization of the chromatin in functional domains, is emerging strongly in these last years. There is a great interest in identifying new insulators because deeper knowledge of these elements can help understand how cis-regulatory elements coordinate the expression of the target genes. However, while insulators are critical in gene regulation and genome functioning, only a few have been reported so far. Here, we describe a new insulator sequence that is located in the 5'UTR of the Drosophila retrotransposon ZAM. We have used an "enhancer blocking assay" to test its effects on the activity of the enhancer in transiently transfected Drosophila S2R(+) cell line. Moreover, we show that the new insulator is able to affect significantly the enhancer-promoter interaction in the human cell line HEK293. These results suggest the possibility of employing the ZAM insulator in gene transfer protocols from insects to mammals in order to counteract the transgene positional and genotoxic effects. PMID- 20364352 TI - Comparison of respiratory function recovery in the early phase after laparoscopy assisted gastrectomy and open gastrectomy. AB - BACKGROUND: Laparoscopic gastrectomy (LAG) is recognized as a less invasive surgery, but no advantage in terms of respiratory function recovery has been demonstrated. We investigated respiratory function recovery in the early period after LAG compared with open gastrectomy (OG) for measuring the recovery of oxygen saturation level (SaO(2)). METHODS: The study population comprised 454 patients who underwent distal gastrectomy or total gastrectomy for preoperatively diagnosed T1N0 gastric cancer: 192 underwent laparoscopy-assisted distal gastrectomy (LADG), 190 underwent open distal gastrectomy (ODG), 42 underwent laparoscopy-assisted total gastrectomy (LATG), and 30 underwent open total gastrectomy (OTG). RESULTS: The number of days until SaO(2) reached 95% or higher in room air was significantly smaller in the LADG group (1.54 days) than in the ODG group (1.81 days; p = 0.010) and also significantly smaller in the LATG group (1.48 days) than in the OTG group (2.03 days; p = 0.043). CONCLUSIONS: LAG patients recovered their oxygenation earlier than OG patients. The laparoscopic procedure might confer a respiratory benefit for gastrectomy patients. PMID- 20364353 TI - Single-incision laparoscopic right hemicolectomy: safety and feasibility in a series of consecutive cases. AB - BACKGROUND: Single-incision laparoscopic colectomy (SILC) is rapidly emerging in the field of minimally invasive colon and rectal surgery. This report presents the safety and feasibility of performing SILC right hemicolectomy with the SILSTM Port Multiple Instrument Access Port. METHODS: Between July 2009 and October 2009, SILC right hemicolectomy was performed for 13 consecutive, unselected patients presenting with benign or malignant pathology. Demographic data, intraoperative parameters, and postoperative outcomes were assessed. RESULTS: For 11 of the 13 patients (84.6%), the SILC procedure was performed with a mean incision length of 3.1 +/- 1.1 cm (range, 2.5-6.0 cm) and a mean operative time of 131.5 +/- 36.2 min (range, 79-180 min). Two cases required conversion to hand assisted technique. Overall, the operative time was found to be significantly longer for the patients with a body mass index (BMI) greater than 25 kg/m(2) (152.1 +/- 26.6 min) compared with the patients with a BMI less than 25 kg/m(2) (93.3 +/- 11.6 min) (p < 0.002). For the subset of patients with malignant disease (five adenocarcinomas and one carcinoid), the mean number of lymph nodes extracted was 26.7 +/- 14.5. There were no intraoperative complications, and the overall mean hospital stay was 2.5 +/- 0.7 days (range, 2-4 days). One postoperative complication occurred (7.7%). CONCLUSION: The SILC procedure is a safe and feasible method for benign and malignant diseases requiring a right hemicolectomy. This method results in a low complication rate and a short postoperative hospital stay. PMID- 20364354 TI - Child and adolescent psychiatry as a clinical neuroscience: a tribute and farewell to Andreas Warnke. PMID- 20364355 TI - Biodegradation of crude oil and pure hydrocarbons by extreme halophilic archaea from hypersaline coasts of the Arabian Gulf. AB - Two extreme halophilic Haloferax strains and one strain each of Halobacterium and Halococcus were isolated from a hypersaline coastal area of the Arabian Gulf on a mineral salt medium with crude oil vapor as a sole source of carbon and energy. These archaea needed at least 1 M NaCl for growth in culture, and grew best in the presence of 4 M NaCl or more. Optimum growth temperatures lied between 40 and 45 degrees C. The four archaea were resistant to the antibiotics chloramphenicol, cycloheximide, nalidixic acid, penicillin, streptomycin and tetracycline. The strains could grow on a wide scope of aliphatic and aromatic (both mono-and polynuclear) hydrocarbons, as sole sources of carbon and energy. Quantitative measurements revealed that these extreme halophilic prokaryotes could biodegrade crude oil (13-47%, depending on the strain and medium salinity), n-octadecane (28 67%) and phenanthrene (13-30%) in culture after 3 weeks of incubation. The rates of biodegradation by all strains were enhanced with increasing NaCl concentration in the medium. Optimal concentration was 3 M NaCl, but even with 4 M NaCl the hydrocarbon-biodegradation rates were higher than with 1 and 2 M NaCl. It was concluded that these archaea could contribute to self-cleaning and bioremediation of oil-polluted hypersaline environments. PMID- 20364356 TI - Haloalkaliphilic spore-forming sulfidogens from soda lake sediments and description of Desulfitispora alkaliphila gen. nov., sp. nov. AB - An anaerobic enrichment with pyruvate as electron donor and thiosulfate at pH 10 and 0.6 M Na(+) inoculated with pasteurized soda lake sediments resulted in a sulfidogenic coculture of two morphotypes of obligately anaerobic haloalkaliphilic endospore-forming clostridia, which were further isolated in pure culture. Strain AHT16 was a thin long rod able to ferment sugars and pyruvate and to respire H(2), formate and pyruvate using thiosulfate and fumarate as electron acceptors and growing optimally at pH 9.5. Thiosulfate was reduced incompletely to sulfide and sulfite. The strain was closely related (99% sequence similarity) to a peptolytic alkaliphilic clostridium Natronincola peptidovorans. Strain AHT17 was a short rod with a restricted respiratory metabolism, growing with pyruvate and lactate as electron donor and sulfite, thiosulfate and elemental sulfur as electron acceptors with a pH optimum 9.5. Thiosulfate was reduced completely via sulfite to sulfide. The ability of AHT17 to use sulfite explained the stability of the original coculture of the two clostridia-one member forming sulfite from thiosulfate and another consuming it. Strain AHT17 formed an independent deep phylogenetic lineage within the Clostridiales and is proposed as a new genus and species Desulfitisporum alkaliphilum gen. nov., sp. nov. (=DSM 22410(T) = UNIQEM U794(T)). PMID- 20364357 TI - Epidural abscess caused by community-associated methicillin-resistant Staphylococcus aureus strain USA300 in Japan. AB - We report a case of epidural abscess caused by community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) strain USA300 in a previously healthy 25-year-old American woman who lived in Japan for more than 1 year. She started to complain of severe headache that continued for about 10 days after improvement of subcutaneous abscesses caused by MRSA. Computed tomography (CT) and magnetic resonance imaging (MRI) showed epidural abscess. As epidural abscess was not improved by treatment with vancomycin and ceftriaxone, craniotomy and drainage were performed, and the severe headache disappeared. Characteristics of the MRSA strain isolated from the abscess were identical to those of strain USA300; multilocus sequence typing sequence type 8, staphylococcal cassette chromosome mec type IVa, Panton-Valentine leukocidin positive, arginine catabolic mobile element positive, and pulsed-field gel electrophoresis type USA300. This may be the first report of epidural abscess caused by USA300 strain in Japan. Because CA MRSA strains, including USA300, have begun to spread in Japan, epidural abscess should be taken into account in the diagnosis of previously healthy patients with persistent headache accompanied by skin lesions. PMID- 20364358 TI - Prevalence and predictive value of anti-cyclic citrullinated protein antibodies for future development of rheumatoid arthritis in early undifferentiated arthritis. AB - The aim of this study is to evaluate the prevalence and predictive value of anti cyclic citrullinated protein (CCP) antibodies as a diagnostic marker for future development of rheumatoid arthritis (RA) in a cohort of patients presenting with undifferentiated arthritis (UA). The study comprised 69 patients (22 males and 47 females) presenting with UA, and 66 healthy subjects as control group. For all patients the following parameters were assessed: swollen joint count (SJC), tender joint count (TJC), and duration of morning stiffness in minutes. Baseline laboratory investigations included erythrocyte sedimentation rate (ESR) first hour, C-reactive protein (CRP), complete blood count, complete liver and kidney function tests, urine analysis, anti-nuclear antibodies, rheumatoid factor (RF), and anti-CCP antibodies. Positive correlations were observed between anti-CCP versus SJC, TJC (p = 0.001), duration of morning stiffness (p = 0.04), ESR first hour, and bone erosive changes (p = 0.001). Anti-CCP showed sensitivity of 57%, specificity of 37.9%, positive predictive value of 65.1%, and negative predictive value of 39.3%. Sensitivity and positive predictive values of anti-CCP are close to those observed for RF. In patients presenting with UA, anti-CCP antibodies may allow prediction of RA, thereby allowing early individualized therapeutic decisions. PMID- 20364359 TI - Protective effect of gastrin-releasing peptide receptor antagonist in carrageenan induced pleural inflammation in rats. AB - OBJECTIVE: We report the effects of the gastrin-releasing peptide (GRP) receptor antagonist RC-3095 in an acute inflammation model induced by carrageenan. METHODS: Male Wistar rats received saline or saline containing 2% lambda carrageenan into the pleural cavity, with some also receiving RC-3095 3 mg/kg subcutaneously, immediately after surgery. Four hours later, the rats were killed and pleural exudate was obtained for evaluation of total cell count, lactate dehydrogenase activity, total protein, cytokines analysis and nitrite/nitrate concentrations; myeloperoxidase (MPO) activity and oxidative stress were evaluated in the lung. RESULTS: RC-3095 exhibited pronounced anti-inflammatory actions by inhibition of leukocyte influx and blockade of MPO, nitrite/nitrate and cytokine levels. Moreover, the results showed that RC-3095 elicits action against oxidative damage in lipids and proteins, as well as increasing cell viability. CONCLUSION: The present findings suggest that GRP plays a role in acute inflammation that can be related with the reduction of oxidative damage and that it could be effective in therapeutic applications. PMID- 20364360 TI - Annular tautomerism: experimental observations and quantum mechanics calculations. AB - The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomeric relative stabilities. The calculated relative energies of tautomers were compared to relative abundances within the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB). The work was focussed on 84 annular tautomeric forms of 34 common ring systems. Good agreement was found between the calculations and the experimental data even if the quantity of these data was limited in many cases. The QM results were compared to those produced by much faster semiempirical calculations. In a search for other sources of the useful experimental data, the relative numbers of known compounds in which prototropic positions were often substituted by heavy atoms were also analysed. A scheme which groups all annular tautomeric transformations into 10 classes was developed. The scheme was designed to encompass a comprehensive set of known and theoretically possible tautomeric ring systems generated as part of a previous study. General trends across analogous ring systems were detected as a result. The calculations and statistics collected on crystallographic data as well as the general trends observed should be useful for the better modelling of annular tautomerism in the applications such as computer-aided drug design, small molecule crystal structure prediction, the naming of compounds and the interpretation of protein-small molecule crystal structures. PMID- 20364361 TI - A nanoencapsulated hypocrellin A prepared by an improved microemulsion method for photodynamic treatment. AB - A new hypocrellin A (HA) encapsulated silica nanoparticles was prepared by an improved microemulsion method based on the unique character of cetyl trimethyl ammonium bromide (CTAB). Stable aqueous dispersions of the HA-loaded nanoparticles, with the diameter about 50 nm, owned superior photo-stability and singlet oxygen generation ability to free HA. In vitro studies demonstrated the active uptake of HA-doped nanoparticles into the cytosol of HeLa (human cervix epithelioid carcinoma) cells. Significant morphology change and phototoxicity to such impregnated tumor cells was observed upon irradiation with light. Thus, the potential of using this method to prepare silica nanoparticles as drug carriers for photodynamic therapy has been demonstrated. PMID- 20364362 TI - Mechanical alloying of biocompatible Co-28Cr-6Mo alloy. AB - We report on an alternative route for the synthesis of crystalline Co-28Cr-6Mo alloy, which could be used for surgical implants. Co, Cr and Mo elemental powders, mixed in an adequate weight relation according to ISO Standard 58342-4 (ISO, 1996), were used for the mechanical alloying (MA) of nano-structured Co alloy. The process was carried out at room temperature in a shaker mixer mill using hardened steel balls and vials as milling media, with a 1:8 ball:powder weight ratio. Crystalline structure characterization of milled powders was carried out by X-ray diffraction in order to analyze the phase transformations as a function of milling time. The aim of this work was to evaluate the alloying mechanism involved in the mechanical alloying of Co-28Cr-6Mo alloy. The evolution of the phase transformations with milling time is reported for each mixture. Results showed that the resultant alloy is a Co-alpha solid solution, successfully obtained by mechanical alloying after a total of 10 h of milling time: first Cr and Mo are mechanically prealloyed for 7 h, and then Co is mixed in for 3 h. In addition, different methods of premixing were studied. The particle size of the powders is reduced with increasing milling time, reaching about 5 mum at 10 h; a longer time promotes the formation of aggregates. The morphology and crystal structure of milled powders as a function of milling time were analyzed by scanning electron microscopy and XR diffraction. PMID- 20364363 TI - Surfactant-modified beta-TCP: structure, properties, and in vitro remineralization of subsurface enamel lesions. AB - A hybrid material comprised of beta-tricalcium phosphate (beta-TCP) and sodium lauryl sulfate (SLS) was prepared using a mechanochemical process, examined using particle size analysis, IR spectroscopy, (31)P, (23)Na, and (13)C solid-state NMR spectroscopy, and calcium dissolution experiments, and probed for in vitro remineralization of subsurface enamel lesions. Our results suggest that while the (31)P environments of beta-TCP remain unchanged during solid-state processing, there is noticeable shifting among the SLS (23)Na and (13)C environments. Therefore, given the structure of beta-TCP, along with our IR examinations and calcium dissolution isotherms, SLS appears to interface strongly with the cation deficient C(3) symmetry site of the beta-TCP hexagonal crystal lattice with probable emphasis placed on the underbonded CaO(3) polyhedra. To demonstrate the utility of the surface-active TCP material in dental applications, we combined the TCP-SLS with 5,000 ppm F (NaF) and evaluated the remineralization potential of subsurface enamel lesions via an in vitro remineralization/demineralization pH cycling dental model. Using surface and longitudinal microhardness measurements, the TCP-SLS plus 5,000 ppm F system was found to significantly boost remineralization of subsurface enamel lesions, with microhardness values increasing up to 30% greater than fluoride alone. PMID- 20364364 TI - Processing and characterization of chitosan microspheres to be used as templates for layer-by-layer assembly. AB - Chitosan (Ch) microspheres have been developed by precipitation method, cross linked with glutaraldehyde and used as a template for layer-by-layer (LBL) deposition of two natural polyelectrolytes. Using a LBL methodology, Ch microspheres were alternately coated with hyaluronic acid (HA) and Ch under mild conditions. The roughness of the Ch-based crosslinked microspheres was characterized by atomic force microscopy (AFM). Morphological characterization was performed by environmental scanning electron microscopy (ESEM), scanning electron microscopy (SEM) and stereolight microscopy. The swelling behaviour of the microspheres demonstrated that the ones with more bilayers presented the highest water uptake and the uncoated cross-linked Ch microspheres showed the lowest uptake capability. Microspheres presented spherical shape with sizes ranging from 510 to 840 mum. ESEM demonstrated that a rougher surface with voids is formed in multilayered microspheres caused by the irregular stacking of the layers. A short term mechanical stability assay was also performed, showing that the LBL procedure with more than five bilayers of HA/Ch over Ch cross-linked microspheres provide higher mechanical stability. PMID- 20364365 TI - The association between second hand smoke and low birth weight and preterm delivery. AB - To determine the association between maternal exposure to SHS and low birth weight and preterm delivery. This cross-sectional study was carried out in the four main governmental hospitals dealing with deliveries in the north of Jordan. A consecutive 8,490 women who delivered in these hospitals between April 2007 and September 2007 were included in the study after excluding those who reported active smoking during the current pregnancy. Pre-structured questionnaire and review of hospital records were used to collect data about maternal background, obstetric history, medical history, and data related to second hand smoke exposure. Overall, 13.8% of women gave birth to a preterm baby and 10.0% gave birth to a low birth weight baby. About 12.6% of women who were exposed to SHS delivered low birth weight babies compared to 7.7% for non exposed women. The rate of preterm delivery among the exposed group was significantly higher than that among the non-exposed group (17.2 vs. 10.6%). In the multivariate analysis, exposure to SHS during pregnancy was significantly associated with increased odds of low birth weight (OR = 1.56 (95% CI 1.31, 1.89)) and preterm delivery (OR = 1.61 (95% CI: 1.30, 1.99)). Exposure of women to SHS during pregnancy is associated with increased odds of low birth weight and preterm delivery. Health care professionals should carry out educational programs to increase awareness and understanding of pregnant women and their husbands about the harmful effects of second hand smoke on birth outcomes. PMID- 20364367 TI - Ovarian cancer: predictors of early-stage diagnosis. AB - OBJECTIVES: Despite the lack of effective screening, almost 20% of women with ovarian cancer are diagnosed at an early stage of disease, when the prognosis is favorable. This study sought to elucidate tumor-related, census-based socioeconomic indicators, and demographic characteristics associated with early diagnosis of epithelial ovarian cancer (EOC). METHODS: The study population included 16,228 women diagnosed with epithelial ovarian cancer from 1996 through 2006 and reported to the California Cancer Registry. Women diagnosed with stage I tumors were compared to those diagnosed with stage III or IV disease with respect to several demographic and tumor-related characteristics. Logistic regression was used to estimate adjusted odds ratios (OR) and associated 95% confidence intervals. RESULTS: Age at diagnosis, tumor histology, tumor size, laterality, and grade were all strongly associated with EOC early stage at diagnosis. However, after adjusting for all relevant factors in this study, other disparities were detected. Compared with white women, the likelihood of being diagnosed with early-stage disease was significantly lower among African Americans (OR = 0.78, 95% CI = 0.55-0.92), and significantly higher among women with private insurance compared to those either uninsured or covered by Medicaid (OR = 1.6, 95% CI = 1.18-2.05). CONCLUSION: These findings suggest that, in addition to tumor biology, disparities in access to care may have a significant effect on the timely diagnosis of epithelial ovarian cancer. PMID- 20364366 TI - Do children with developmental disabilities and mental health conditions have greater difficulty using health services than children with physical disorders? AB - The objective of this study is to determine whether achievement of the Maternal and Child Health Bureau core outcome ease of use of health services differs between children with developmental disabilities, mental health conditions and physical disorders. We analyzed data from the 2005 National Survey of Children with Special Health Care Needs. Children with special health care needs were classified into 4 health condition groups: developmental disabilities (DD), mental health conditions (MH), physical disorders (PD) and multiple conditions. The outcome measure was 'difficulty using services'. We conducted bivariate and multivariate analyses to determine the associations between the health condition groups and the outcome. Of the CSHCN included in the study, 2.6% had DD, 12.9% had MH, 49.9% had PD and 34.6% belonged to multiple conditions group. Four percent of CSHCN with PD, 17% of those with DD, 13% of those with MH and 20% of those in the multiple conditions group had difficulty using services. In multivariate analyses, CSHCN with DD had 2.3 times and MH conditions had 2.6 times the odds of having difficulty using services compared to those with PD. Existing programs for CSHCN should be evaluated for the adequacy of services provided to children with DD and MH. Future studies should evaluate how developmental disabilities and mental health policies affect navigating the health care system for this population. PMID- 20364368 TI - A study of the effects of chromium exposure on the growth of Pseudokirchneriella subcapitata (Korshikov) hindak evaluated by Central Composite Design and Response Surface Methodology. AB - The aim of this study was to evaluate the effects of chromium exposure on the growth of P. subcapitata using the Central Composite Design (CCD) and Response Surface Methodology (RSM). The highest values for algal density and biomass were obtained in the longest exposure times and for the lowest chromium concentrations. The CCD used for the analysis of treatment combinations showed that a second order polynomial regression model was in good agreement with experimental results, with R (2) = 81.50 and 89.90; for algal density and biomass (p < 0.05), respectively. Only the exposure time was significant for algal density. For chlorophyll, in contrast, the exposure time, chromium concentration and their interaction significantly affected the growth of P. subcapitata. The findings confirmed the sensitivity of P. subcapitata to chromium (VI), which makes it a suitable bioindicator of environmental contamination for this metal. PMID- 20364369 TI - Multicomponent reactions of amines with aldehydes and H(2)S as efficient route to heterocycles and thioaza macrocycles. AB - Here we provide new experimental results on multicomponent reactions of amines with aldehydes and H(2)S in the directed synthesis of functionally-substituted 1,3-thiazetidines, 1,3,5-dithiazinanes, 1,3,5-thiadiazinanes, 1,5-dithia-3,7 diazacyclooctanes, and thioaza macrocycles. X-ray analysis gave insight into the structure of the synthesized compounds. New kinds of multicomponent reactions (MCR) have been discovered and characterized. PMID- 20364370 TI - Green chemistry approaches to the regioselective synthesis of spiro heterobicyclic rings using iodine as a new and efficient catalyst under solvent free conditions. AB - Iodine catalyzes the pseudo four-component reaction of an aldehyde, a urea or thiourea, and cyclic 1,3-dicarbonyl compounds under microwave irradiation in a solvent-free condition to yield various sigma symmetric spiro heterobicyclic rings in excellent yields. PMID- 20364371 TI - Paracoccidioides brasiliensis uses endogenous and exogenous arachidonic acid for PGE x production. AB - Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids during fungal infections plays a critical role on fungal biology as well as on host immune response modulation. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, Bt79, Pb192) produce prostaglandin E(x) (PGE(x)). Moreover, we asked if P. brasiliensis could use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) enzyme, as reported for mammalian cells. A possible association between this prostanoid and fungus viability was also assessed. Our results showed that all strains, independently of their virulence, produce high PGE(x) levels on 4 h culture that were reduced after 8 h. However, in both culture times, higher prostanoid levels were detected after supplementation of medium with exogenous AA. Treatment with indomethacin, a COX inhibitor, induced a reduction on PGEx, as well as in fungus viability. The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability. PMID- 20364372 TI - Chromosome number variation of phytoestrogen-producing Curcuma (Zingiberaceae) from Thailand. AB - Wan-chak-motluk is a Thai local name for native species of Curcuma (Zingiberaceae) that produce phytoestrogen in their rhizomes. Wan-chak-motluk has long been used in Thai traditional medicine for treatment of illness in the uterus and ovarian hormone deficit, and therefore it is cultivated for economic purposes throughout Thailand. The rhizome morphology of wan-chak-motluk is highly variable and this may be related to its medicinal properties. Thus, this study aimed to identify and classify wan-chak-motluk collected from cultivation sites in 16 provinces of Thailand. Chromosome numbers, together with inflorescent, floral, and leaf morphology, were used to separate wan-chak-motluk into five cultivars belonging to three species: C. comosa, C. elata, and C. latifolia. Curcuma comosa has short (2-5 cm) peduncle, glabrous lower leaf, and consists of two cultivars. One cultivar has a cylindrical spike 13-17 cm long and 5-8 cm wide, whereas the cylindrical spike of the other cultivar is shorter (10-15 cm) but larger (8-12 cm). The former cultivar has 2n = 42 and the latter has 2n = 63, seldom 2n = 62 or 64. Both C. elata and C. latifolia have long (10-25 cm) peduncle and pubescent lower leaf. They differ in that C. latifolia has 2n = 63 and 84 with a red path along the midrib, whereas C. elata has 2n = 63 without a red path along the midrib. This study shows that chromosome numbers can be used to accurately verify the taxonomic identification of wan-chak-motluk. PMID- 20364373 TI - Ability of 18F-FDG PET/CT to diagnose recurrent colorectal cancer in patients with elevated CEA concentrations. AB - OBJECTIVE: Elevated levels of serum carcinoembryonic antigen (CEA) in patients with colorectal cancer (CRC) during follow-up suggest recurrence, which can be visualized by (18)F-FDG PET/CT. Since the magnitude of CEA elevation reflects cancer volume, the ability of PET/CT to detect recurrence in patients with only mildly elevated CEA might be limited. However, the accuracy of PET/CT in detecting recurrence associated with elevated CEA has not been fully assessed. We retrospectively evaluated the diagnostic performance of (18)F-FDG PET/CT postoperatively relative to CEA levels among patients with CRC. METHODS: We visually assessed 75 PET/CT evaluations of 57 postoperative patients with CEA >5.0 ng/ml. Tumor volumes were also determined using image analysis software. The final diagnosis was confirmed based on histopathological findings, or at least on 6 months of clinical follow-up. RESULTS: Two lung cancers were excluded and we finally analyzed data from 73 of the 75 PET/CT evaluations. Recurrences were diagnosed in 54 (prevalence 74%). The sensitivity and specificity of PET/CT to detect recurrence was 50/54 (93%) and 14/19 (74%), respectively. The positive and negative predictive values were 91 and 78%, respectively, and the positive and negative likelihood ratios were 3.52 and 0.10, respectively. Values for the sensitivity of PET/CT were 88 and 95%, and those for specificity were 78 and 70%, at serum CEA concentrations of 5-10 and >10 ng/ml, respectively. Serum CEA (r = 0.500, p < 0.001) significantly correlated with cancer volumes. CONCLUSIONS: The present findings showed that (18)F-FDG PET/CT could accurately detect recurrent CRC irrespective of the elevated CEA concentration. PMID- 20364374 TI - Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models. AB - OBJECTIVE: Dopamine transporter (DAT) is a reuptake carrier of dopamine at presynapse that regulates dopaminergic neural transmission. [(11)C]PE2I is a cocaine analog developed as a potent positron emission tomography (PET) ligand for DAT with high selectivity. The aim of this study was to evaluate the applicability of quantification methods using reference tissue models for [(11)C]PE2I. METHODS: Dynamic PET scans were performed in 6 young healthy male volunteers after an intravenous bolus injection of [(11)C]PE2I. Metabolite corrected arterial plasma-input functions were obtained. Compartment model analysis and plasma-input Logan analysis were performed to determine the kinetic parameters and distribution volume (V (T)). The distribution volume ratio (DVR) was calculated as the ratio of V (T) in the cerebral region to that in the cerebellum. DVRs were also determined by the original multilinear reference tissue model method (MRTMo) and the simplified reference tissue model method (SRTM), comparing the results with those obtained from graphical analysis using arterial input function. To estimate errors in DVR calculated using the reference tissue model, a simulation study that focused on cerebellar kinetics and scan duration was performed. RESULTS: The highest [(11)C]PE2I binding was observed in the striatum, followed by the midbrain and thalamus. The 2-tissue model was preferable to the 1-tissue model for describing the [(11)C]PE2I kinetics in the cerebellum. Both the measured and 90-min simulated data showed that reference tissue models caused an underestimation of DVR in the striatum. The simulation showed that 90-min scan duration was insufficient when cerebellar kinetics was described as a 1-tissue model. Nevertheless, DVR values determined by MRTMo and SRTM were in good agreement with those by the graphical approach in other lower binding regions. CONCLUSION: Due to the [(11)C]PE2I kinetics in the cerebellum and limited scan duration for (11)C, MRTMo and SRTM underestimated the striatal DVR. Despite this limitation, the present study demonstrated the applicability of reference tissue models. Since DAT in the midbrain and thalamus is of interest in the pathophysiology of neuropsychiatric disease, this noninvasive quantitative analysis will be useful for clinical investigations. PMID- 20364375 TI - Genetic diversity and population structure of a diverse set of rice germplasm for association mapping. AB - Germplasm diversity is the mainstay for crop improvement and genetic dissection of complex traits. Understanding genetic diversity, population structure, and the level and distribution of linkage disequilibrium (LD) in target populations is of great importance and a prerequisite for association mapping. In this study, 100 genome-wide simple sequence repeat (SSR) markers were used to assess genetic diversity, population structure, and LD of 416 rice accessions including landraces, cultivars and breeding lines collected mostly in China. A model-based population structure analysis divided the rice materials into seven subpopulations. 63% of the SSR pairs in these accessions were in LD, which was mostly due to an overall population structure, since the number of locus pairs in LD was reduced sharply within each subpopulation, with the SSR pairs in LD ranging from 5.9 to 22.9%. Among those SSR pairs showing significant LD, the intrachromosomal LD had an average of 25-50 cM in different subpopulations. Analysis of the phenotypic diversity of 25 traits showed that the population structure accounted for an average of 22.4% of phenotypic variation. An example association mapping for starch quality traits using both the candidate gene mapping and genome-wide mapping strategies based on the estimated population structure was conducted. Candidate gene mapping confirmed that the Wx and starch synthase IIa (SSIIa) genes could be identified as strongly associated with apparent amylose content (AAC) and pasting temperature (PT), respectively. More importantly, we revealed that the Wx gene was also strongly associated with PT. In addition to the major genes, we found five and seven SSRs were associated with AAC and PT, respectively, some of which have not been detected in previous linkage mapping studies. The results suggested that the population may be useful for the genome-wide marker-trait association mapping. This new association population has the potential to identify quantitative trait loci (QTL) with small effects, which will aid in dissecting complex traits and in exploiting the rich diversity present in rice germplasm. PMID- 20364376 TI - Isolated chromosomes as a new and efficient source of DArT markers for the saturation of genetic maps. AB - We describe how the diversity arrays technology (DArT) can be coupled with chromosome sorting to increase the density of genetic maps in specific genome regions. Chromosome 3B and the short arm of chromosome 1B (1BS) of wheat were isolated by flow cytometric sorting and used to develop chromosome- and chromosome arm-enriched genotyping arrays containing 2,688 3B clones and 384 1BS clones. Linkage analysis showed that 553 of the 711 polymorphic 3B-derived markers (78%) mapped to chromosome 3B, and 59 of the 68 polymorphic 1BS-derived markers (87%) mapped to chromosome 1BS, confirming the efficiency of the chromosome-sorting approach. To demonstrate the potential for saturation of genetic maps, we constructed a consensus map of chromosome 3B using 19 mapping populations, including some that were genotyped with the 3B-enriched array. The 3B-derived DArT markers doubled the number of genetic loci covered. The resulting consensus map, probably the densest genetic map of 3B available to this date, contains 939 markers (779 DArTs and 160 other markers) that segregate on 304 genetically distinct loci. Importantly, only 2,688 3B-derived clones (probes) had to be screened to obtain almost twice as many polymorphic 3B markers (510) as identified by screening approximately 70,000 whole genome-derived clones (269). Since an enriched DArT array can be developed from less than 5 ng of chromosomal DNA, a quantity which can be obtained within 1 h of sorting, this approach can be readily applied to any crop for which chromosome sorting is available. PMID- 20364377 TI - Identification of differentially expressed genes at two key endosperm development stages using two maize inbreds with large and small grain and integration with detected QTL for grain weight. AB - Maize endosperm accounts for more than 80% of the grain weight. Cell division and grain filling are the two key stages for endosperm development. Previous studies showed that gene expression during differential stages in endosperm development is greatly different. However, information on systematic identification and characterization of the differentially expressed genes between the two stages are limited. In this study, suppression subtractive hybridization (SSH) was used to generate four subtracted cDNA libraries for the two stages using two maize inbreds with large and small grain. Totally, 4,784 differentially expressed sequence tags (ESTs) were sequenced and 902 were non-redundant, which consisted of 344 unique ESTs. Among them 192 had high sequence similarity to the GenBank entries and represent diverse of functional categories, such as metabolism, cell growth/division, transcription, signal transduction, protein destination/storage, protein synthesis and others. The expression patterns of 75.7% SSH-derived cDNAs were confirmed by reverse Northern blot and semi-quantitative reverse transcription polymerase chain reaction, and exhibited the similar results (75.0%). Genes differentially expressed between two key stages for the two inbreds were involved in diverse physiological process pathway, which might be responsible for the formation of grain weight. 43.8% (70 of the 160 unique ESTs) of the identified ESTs were assigned to 39 chromosome bins distributed over all ten maize chromosomes. Eleven ESTs were found to co-localize with previous detected QTLs for grain weight, which might be considered as the candidate genes of grain weight for further study. PMID- 20364378 TI - Local delivery of recombinant vaccinia virus encoding for neu counteracts growth of mammary tumors more efficiently than systemic delivery in neu transgenic mice. AB - Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: (a) carcinogenesis stage at which the vaccination was initiated; (b) number of vaccinations and (c) route of delivery (systemic vs. local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c.) and intramammary gland (im.g.) injection with rV neuT or V-wt (wild-type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. The im.g. vaccination was more effective than the s.c. vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cells apoptosis and antibody-dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g. vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cells apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus. PMID- 20364379 TI - Assessing surface water quality and its relation with urban land cover changes in the Lake Calumet area, Greater Chicago. AB - Urban land use and land cover change significantly affect spatial and temporal patterns of runoff, which in turn impacts surface water quality. With the exponential growth in urban areas over the past three decades, changes in land use and land cover to cater for the growth of cities has been a conspicuous spectacle in urban spaces. The main goal of this study was to assess the impacts of land cover change on runoff and surface water quality using a partial area hydrology framework. The study employed ArcHydro GIS extension and a modified version of Long-Term Hydrologic and Nonpoint Source Pollution model (L-THIA-NPS) in estimating runoff and nonpoint source pollutant concentration around Lake Calumet between 1992 and 2001. Data employed include National Land Cover Data set, rainfall data, digital elevation model (DEM), Soil Survey Geographic (SSURGO) data, and The United States Environmental Protection Agency's STORET (storage and retrieval) water quality data. The model was able to predict surface water quality reasonably well over the study period. Sensitivity analysis facilitated a manual calibration of the model. Model validation was executed by comparing simulated results following calibration and observed water quality data for the study area. The study demonstrates that the level of concentration of nonpoint source pollutants in surface water within an urban watershed heavily depends on the spatiotemporal variations in areas that contribute towards runoff compared to the spatial extent of change in major land use/land cover. PMID- 20364380 TI - Necessary and sufficient conditions for the existence of an optimisation principle in evolution. AB - This paper presents a necessary condition for the existence of a numerical quantity optimised by evolution by natural selection, which also turns out to be a sufficient condition under rather general conditions. As a corollary, a related criterion with a particularly intuitive graphical interpretation in terms of pairwise invadability plots is obtained. PMID- 20364381 TI - A case of ANCA-associated vasculitis presenting with calf claudication. AB - Wegener's granulomatosis (WG), Churg-Strauss syndrome, and microscopic polyangiitis (MPA) are closely related small vessel vasculitides characterized by anti-neutrophil cytoplasmic antibodies (ANCA). Although there were some reports of MPA presenting with claudication, there are very few reports on WG presenting with claudication of calf muscles. We report an unusual case of ANCA-associated vasculitis in a 75-year-old man who presented with bilateral calf claudication. Comprehensive evaluations, including electromyography, nerve conduction study, lower extremity magnetic resonance imaging, and Doppler scan, did not reveal any other cause of bilateral calf claudication. P-ANCA and anti-myeloperoxidase antibody was positive, but the anti-proteinase 3 antibody was negative. Chest computed tomography scan showed subpleural honeycombing and reticulation, predominantly in both basal lung areas. Biopsy of the calf muscle showed granulomatous vasculitis. Kidney biopsy was also performed which revealed focal necrotizing glomerulonephritis. Our patient does not exhibit typical clinical features for WG, but histopathologic findings of necrotizing granulomatous vasculitis in calf muscle biopsy is highly suggestive of WG. PMID- 20364382 TI - Multi-modal treatment for metastatic renal cancer: the role of surgery. AB - Surgical intervention in the patients with metastatic renal cancer can occur in two settings: (1) to render a patient clinically free of all sites of primary disease and metastases, termed nephrectomy/metastasectomy, or (2) to resect the primary tumor in the face of unresectable metastatic disease prior to the initiation of systemic therapy, termed cytoreductive nephrectomy. Carefully selected patients with good performance status undergoing nephrectomy and subsequent metastasectomy may experience prolonged survival in the range of 30 months, which could be attributed to a combination of patient selection factors and the surgical resections. Randomized clinical trials from the United States and Europe have demonstrated a small but significant survival benefit to cytoreductive nephrectomy and cytokine therapy versus cytokine therapy alone which is measured in the range of 3-6 months and associated with overall survival of approximately 12 months. The precise mechanism by which cytoreductive nephrectomy improves survival is not known but may relate to reduction in the large primary immunosuppressive burden. Patient selection factors including performance status and serum factors (Hgb, corrected Ca++, LDH) stratify metastatic patients into risk groups, which are strongly associated with survival time in both medically and surgically treated patients with metastatic renal cancer. The development of multi-kinase and mTOR inhibitors has markedly improved survival in treatment naive and previously treated patients with metastatic renal cancer , and these agents are currently under active clinical investigation in the neo-adjuvant and adjuvant setting. PMID- 20364383 TI - Intraepidermal injection of dissociated epidermal cell suspension improves vitiligo. AB - This study was initiated to evaluate the safety and effectiveness of intraepidermal injection of dissociated epidermal cells into the lesions of stable vitiligo patients. Autologous dissociated epidermal cell suspensions were injected intraepidermally into 10 stable vitiligo patients. None of the patients received adjuvant therapy. The response was evaluated as: marked (76-100%), moderate (51-75%), mild (26-50%) and minimal repigmentation (0-25%). Transmission electron microscopy was used to evaluate the transplanted cells and immunohistochemical staining with HMB-45 was performed to assess the repigmentation in vivo. In all cases, repigmentation started during the 4-week period after transplantation. Six months after transplantation, a marked repigmentation in four (40%), moderate repigmentation in two (20%) and mild repigmentation in two (20%) patients were observed. Two (20%) patients with white patches on their lids showed minimal repigmentation. No side effects were observed in any patients. Interestingly, repigmentation of gray hair in one patient, 4 months post transplantation was observed. Analysis of the ultrastructure of transplanted cells showed 1.5% of the cells had melanocyte morphology. HMB-45 positive cells were observed after cell transplantation. This method is an effective, simple and safe therapeutic option for stable vitiligo lesions. PMID- 20364384 TI - Sound-induced vertigo due to bone dehiscence of the lateral semicircular canal. AB - Dehiscence of the lateral semicircular canal (LSCD) has been reported much but mainly in association with cholesteatoma and canal wall down mastoidectomy, while idiopathic LSCD was rarely reported. Bassim reported one case with lateral semicircular canal dehiscence, but presented no vestibular or auditory symptoms. The patient in this study complained significant sound-induced vertigo and autophony in his right ear. The axis of nystagmus was orthogonal to the lateral semicircular canal, and no torsional or vertical motions were observed, so pathology of the lateral semicircular canal was preferentially considered. Benign paroxysmal positional vertigo was excluded since vertigo attacks had no relation to the change of head position. The dehiscence of the right lateral semicircular canal was then confirmed through the high-resolution temporal bone computer tomography scan and the reconstructed images. The cause of the LSCD is poorly understood, since no history of head trauma, otological infection or surgery was documented. PMID- 20364385 TI - Block training periodization in alpine skiing: effects of 11-day HIT on VO2max and performance. AB - Attempting to achieve the high diversity of training goals in modern competitive alpine skiing simultaneously can be difficult and may lead to compromised overall adaptation. Therefore, we investigated the effect of block training periodization on maximal oxygen consumption (VO2max) and parameters of exercise performance in elite junior alpine skiers. Six female and 15 male athletes were assigned to high intensity interval (IT, N = 13) or control training groups (CT, N = 8). IT performed 15 high-intensity aerobic interval (HIT) sessions in 11 days. Sessions were 4 x 4 min at 90-95% of maximal heart rate separated by 3-min recovery periods. CT continued their conventionally mixed training, containing endurance and strength sessions. Before and 7 days after training, subjects performed a ramp incremental test followed by a high-intensity time-to-exhaustion (tlim) test both on a cycle ergometer, a 90-s high-box jump test as well as countermovement (CMJ) and squat jumps (SJ) on a force plate. IT significantly improved relative VO2max by 6.0% (P < 0.01; male +7.5%, female +2.1%), relative peak power output by 5.5% (P < 0.01) and power output at ventilatory threshold 2 by 9.6% (P < 0.01). No changes occurred for these measures in CT. tlim remained unchanged in both groups. High-box jump performance was significantly improved in males of IT only (4.9%, P < 0.05). Jump peak power (CMJ -4.8%, SJ -4.1%; P < 0.01), but not height decreased in IT only. For competitive alpine skiers, block periodization of HIT offers a promising way to efficiently improve VO2max and performance. Compromised explosive jump performance might be associated with persisting muscle fatigue. PMID- 20364387 TI - The bidirectional cytomegalovirus immediate/early promoter is regulated by Hog1 and the stress transcription factors Sko1 and Hot1 in yeast. AB - The work presented here intends to address the question of whether the immediate/early promoter of cytomegalovirus (CMV), which is widely used for expressing transgenes in eukaryotic cells, yields a constitutive expression of the transgenes under stress conditions in Saccharomyces cerevisiae cells. This information would also be relevant because in the tetracycline-regulated expression (tetO) system, which is one of the first choices for studying gene function from yeast to human cells, the CMV promoter controls the expression of the tetO transactivator. We found that the CMV promoter in yeast cells is bidirectionally induced by osmotic stress and in glycerol media. The mitogen activated protein (MAP) kinase Hog1 controls CMV activation by osmotic stress through the ATF/CRE-related transcription factor Sko1 and the yeast osmostress factor Hot1. Our results indicate that the CMV and tetO expression systems respond to external signals and this should be considered before using these systems in yeast. Moreover, our results also suggest that CMV could be regulated by the intracellular glucose concentration in human cells. PMID- 20364388 TI - Distribution patterns of wintering sea ducks in relation to the North Atlantic Oscillation and local environmental characteristics. AB - Twelve species of North American sea ducks (Tribe Mergini) winter off the eastern coast of the United States and Canada. Yet, despite their seasonal proximity to urbanized areas in this region, there is limited information on patterns of wintering sea duck habitat use. It is difficult to gather information on sea ducks because of the relative inaccessibility of their offshore locations, their high degree of mobility, and their aggregated distributions. To characterize environmental conditions that affect wintering distributions, as well as their geographic ranges, we analyzed count data on five species of sea ducks (black scoters Melanitta nigra americana, surf scoters M. perspicillata, white-winged scoters M. fusca, common eiders Somateria mollissima, and long-tailed ducks Clangula hyemalis) that were collected during the Atlantic Flyway Sea Duck Survey for ten years starting in the early 1990s. We modeled count data for each species within ten-nautical-mile linear survey segments using a zero-inflated negative binomial model that included four local-scale habitat covariates (sea surface temperature, mean bottom depth, maximum bottom slope, and a variable to indicate if the segment was in a bay or not), one broad-scale covariate (the North Atlantic Oscillation), and a temporal correlation component. Our results indicate that species distributions have strong latitudinal gradients and consistency in local habitat use. The North Atlantic Oscillation was the only environmental covariate that had a significant (but variable) effect on the expected count for all five species, suggesting that broad-scale climatic conditions may be directly or indirectly important to the distributions of wintering sea ducks. Our results provide critical information on species-habitat associations, elucidate the complicated relationship between the North Atlantic Oscillation, sea surface temperature, and local sea duck abundances, and should be useful in assessing the impacts of climate change on seabirds. PMID- 20364389 TI - King eiders use an income strategy for egg production: a case study for incorporating individual dietary variation into nutrient allocation research. AB - The use of stored nutrients for reproduction represents an important component of life-history variation. Recent studies from several species have used stable isotopes to estimate the reliance on stored body reserves in reproduction. Such approaches rely on population-level dietary endpoints to characterize stored reserves ("capital") and current diet ("income"). Individual variation in diet choice has so far not been incorporated in such approaches, but is crucial for assessing variation in nutrient allocation strategies. We investigated nutrient allocation to egg production in a large-bodied sea duck in northern Alaska, the king eider (Somateria spectabilis). We first used Bayesian isotopic mixing models to quantify at the population level the amount of endogenous carbon and nitrogen invested into egg proteins based on carbon and nitrogen isotope ratios. We then defined the isotopic signature of the current diet of every nesting female based on isotope ratios of eggshell membranes, because diets varied isotopically among individual king eiders on breeding grounds. We used these individual-based dietary isotope signals to characterize nutrient allocation for each female in the study population. At the population level, the Bayesian and the individual based approaches yielded identical results, and showed that king eiders used an income strategy for the synthesis of egg proteins. The majority of the carbon and nitrogen in albumen (C: 86 +/- 18%, N: 99 +/- 1%) and the nitrogen in lipid-free yolk (90 +/- 15%) were derived from food consumed on breeding grounds. Carbon in lipid-free yolk derived evenly from endogenous sources and current diet (exogenous C: 54 +/- 24%), but source contribution was highly variable among individual females. These results suggest that even large-bodied birds traditionally viewed as capital breeders use exogenous nutrients for reproduction. We recommend that investigations of nutrient allocation should incorporate individual variation into mixing models to reveal intraspecific variation in reproductive strategies. PMID- 20364390 TI - Seed consumption and dispersal of ant-dispersed plants by slugs. AB - In beech-dominated forests in Central Europe, many spring geophytes show adaptations to seed dispersal by ants (myrmecochory). Ants, however, can be rare in such moist forests. Motivated by observations of slug feeding on seeds we investigated the seed consumption of two plant species, Anemone nemorosa and Asarum europaeum, by slugs, in a series of experiments. In a seed predation experiment in a beech forest, we found that seed removal was strongly reduced when gastropods were excluded from the seed depots. The contribution of insects, including ants, and rodents to seed removal was relatively less but differed between May and July. In the laboratory, slug species, in particular Arion sp., consumed seeds of both plant species. Slugs either consumed the elaiosomes of seeds or swallowed seeds intact. Swallowed seeds were defecated undamaged and germinated as well as control seeds when buried overwinter, indicating the potential for seed dispersal by slugs. We also recovered seeds of myrmecochores in the faeces of several slugs caught in forests. In a slug release experiment in the forest, slugs moved up to 14.6 m (mean 4.4 m) in 15 h, which is the median gut passage time of seeds based on measurements made in the laboratory. We also found that when slug-defecated seeds were offered to rodents, these were less attractive than control seeds, suggesting that passage through the slug gut reduces seed predation risk. Our results demonstrate that slugs are significant consumers of elaiosomes or entire seeds of ant-dispersed plants and that they can function as seed dispersers of these plants. PMID- 20364391 TI - Discal cysts of the lumbar spine: report of five cases and review of the literature. AB - Discal cysts are rare causes of low back pain and radiculopathy. Only few reports in the literature describe these pathologies. In this article, the authors report five cases (3 males and 2 females) of lumbar discal cysts treated surgically by microdiscectomy. These patients were admitted with a history of back pain and/or sciatalgia. Magnetic resonance imaging of the lumbar spine of all patients revealed lumbar discal cysts, causing compression to the spinal dura and roots. All patients were treated by partial hemilaminectomy and microscopic cyst resection. Postoperatively, the complaints showed improvement, and the patients were discharged with no complications. The cases of lumbar discal cysts are described in the literature as individual case reports, therefore; the authors performed a wide systemic review of all these cases published in PubMed and MedLine, including the patients in the present report. The data of all patients were analyzed to obtain statistically based estimated information about the incidence, the epidemiology, the natural history and the optimum management of these lesions. PMID- 20364392 TI - A meta-analysis of artificial total disc replacement versus fusion for lumbar degenerative disc disease. AB - Lumbar fusion has been developed for several decades and became the standard surgical treatment for symptomatic lumbar degenerative disc disease (DDD). Artificial total disc replacement (TDR), as an alternative for spinal arthrodesis, is becoming more commonly employed treating lumbar DDD. It is still uncertain whether TDR is more effective and safer than lumbar fusion. To systematically compare the effectiveness and safety of TDR to that of the fusion for the treatment of lumbar DDD, we performed a meta-analysis. Cochrane review methods were used to analyze all relevant randomized controlled trials published up to July 2009. Five relevant randomized controlled trials involving 837 patients were identified. Patients in TDR group have slightly better functioning and less back or leg pain without clinical significance, and significantly higher satisfaction status in TDR group compared with lumbar fusion group at the 2-year follow-up. But these outcomes are highly influenced by the study with BAK cage interbody fusion, the function/pain and patient satisfaction status are no longer significantly different between two groups after excluding this study. At 5 years, these outcomes are not significantly different between comparing groups. The complication and reoperation rate of two groups are similar both at 2 and at 5 years. In conclusion, TDR does not show significant superiority for the treatment of lumbar DDD compared with fusion. The benefits of motion preservation and the long-term complications are still unable to be concluded. More high quality RCTs with long-term follow-up are needed. PMID- 20364393 TI - Role of oxidative stress in the antitumoral action of a new vanadyl(IV) complex with the flavonoid chrysin in two osteoblast cell lines: relationship with the radical scavenger activity. AB - The new complex [VO(chrysin)(2)EtOH](2) (VOchrys) has been synthesized and thoroughly characterized. Fourier transform IR, UV-vis, diffuse reflectance, and EPR spectroscopies as well as elemental analysis and thermal measurements were performed. In solution, different species could be detected by EPR spectroscopy as a function of the ligand-to-metal ratio. The stoichiometry of the chelate complex formed at pH 5 was also determined by spectrophotometric titrations. Since flavonoids are natural antioxidant compounds, the antioxidant capacity of chrysin and its vanadyl(IV) complex was investigated using different radicals. Chrysin and its complex were not able to diminish the level of superoxide and 1,1 diphenyl-2-picrylhydrazyl radicals to a great extent. In contrast, they were strong scavengers for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt radical cations and OH. radicals with a greater potency for VOchrys. Taking into account their selective antioxidant properties, we investigated the bioactivity of these compounds in two osteoblast-like cells in culture. Chrysin and VOchrys caused an inhibition of cell proliferation in MC3T3E1 normal osteoblasts and UMR106 tumor cells in a dose-response manner, with a greater effect in the latter cell line. The generation of reactive oxygen species (ROS) was evaluated in both cell lines and a correlation could be established between the antiproliferative effects of chrysin and the increase in the ROS levels. The complex did not generate types of ROS that can be detected by the dihydrorhodamine 123 technique so the antiproliferative effect may be attributed to the formation of other radicals such as superoxide, which is not detected by this probe. The morphological alterations were in agreement with these changes. PMID- 20364394 TI - The persistence of T cell memory. AB - T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years, numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming. However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell receptor signaling and inflammation control CD8 memory differentiation. PMID- 20364396 TI - Factors enhancing L-valine production by the growth-limited L-isoleucine auxotrophic strain Corynebacterium glutamicum DeltailvA DeltapanB ilvNM13 (pECKAilvBNC). AB - Cell growth limitation is known to be an important condition that enhances L: valine synthesis in Corynebacterium glutamicum recombinant strains with L: isoleucine auxotrophy. To identify whether it is the limited availability of L: isoleucine itself or the L: -isoleucine limitation-induced rel-dependent ppGpp mediated stringent response that is essential for the enhancement of L: -valine synthesis in growth-limited C. glutamicum cells, we deleted the rel gene, thereby constructing a relaxed (rel (-) ) C. glutamicum DeltailvA DeltapanB Deltarel ilvNM13 (pECKAilvBNC) strain. Variations in enzyme activity and L: -valine synthesis in rel (+) and rel (-) strains under conditions of L: -isoleucine excess and limitation were investigated. A sharp increase in acetohydroxy acid synthase (AHAS) activity, a slight increase in acetohydroxyacid isomeroreductase (AHAIR) activity, and a dramatic increase in L: -valine synthesis were observed in both rel (+) and rel (-) cells exposed to L: -isoleucine limitation. Although the positive effect of induction of the stringent response on AHAS and AHAIR upregulation in cells was not confirmed, we found the stringent response to be beneficial for maintaining increased AHAS, dihydroxyacid dehydratase, and transaminase B activity and L: -valine synthesis in cells during the stationary growth phase. PMID- 20364397 TI - Superoxide dismutase, protease and lipase expression in clinical isolates of Staphylococcus aureus: a tool for antimicrobial drug discovery. AB - The rising incidents of invasive infections due to multidrug resistant Staphylococcus aureus necessitate the exploration of newer targets for development of antibiotics. Pathogenicity of S. aureus is attributed to a wide range of virulence factors. The aim of this study was to screen the production of three virulence factors viz. extracellular protease, extracellular lipase and superoxide dismutase in human pathogenic strains of S. aureus for development of a test panel which could aid in screening of natural products of plant and microbial origin. 27 clinical isolates were compared for their enzyme expression profiles of which eight were finally selected. Sau G5 was the only protease producing organism selected in the test panel, while Sau G3 and Sau G9 were best SOD producers and Sau G16, Sau G18, Sau G22, Sau A5 and Sau A2 exhibited highest expression among different groups of clinical staphylococci. PMID- 20364398 TI - VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population. AB - Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has been shown to play a significant role in neovascularization during inflammation in atherosclerotic plaques, formation of collateral vessels to an area of ischemic myocardium and neovascularization at the edges of a myocardial infarction during its repair. Interleukin-4 (IL-4) has important role in immune cell chemotaxis, formation of endothelial cell adhesion molecules and has numerous anti-inflammatory effects which prevent the complications of atherosclerosis, the primary cause of coronary heart disease (CHD). In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). To analyze polymorphic alleles, ARMS-PCR and RFLP techniques were used. Multiple logistic regression analysis was carried out with statistical software. GG genotype was associated with a decreased risk of development of CHD (OR 0.22, 95% CI 0.12 0.38, P < 0.001). However, A allele showed an increased risk whereas G allele decreased the risk of CHD with diabetes mellitus, hypertension, chronic mental stress and positive familial history of myocardial infarction (MI)/CHD. GG genotype was found to have protective effect with alcohol intake (OR 0.34, 95% CI 0.14-0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04-0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes. PMID- 20364395 TI - Bioinformatics and molecular modeling in glycobiology. AB - The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein-carbohydrate interaction are reviewed. PMID- 20364399 TI - A sensitive polymerase chain reaction-based method for detection and quantification of metastasis in human xenograft mouse models. AB - Tumor cell dissemination to distant organs accounts for the majority of cancer related deaths. Analysis of the stepwise process of metastasis formation and progression might provide novel therapeutic strategies for the treatment of disseminated cancer. However, studies with both biological and therapeutic endpoints would require highly sensitive and specific methods for precise quantification of the metastatic tumor burden in vivo. We have developed a quantitative real-time PCR-based assay for the detection and quantification of human tumor cells disseminated in mouse organs. The method relies on the parallel amplification of unique, species-specific, conserved and non-transcribed sequences in the mouse and human genomes. We tested the method in xenograft models to assess the metastatic potential of various cancer cell lines, the impact of injection modality and cell type on organ distribution, and the early stages of metastasis implantation and progression. With this method, we observed clear quantitative differences among colon cancer cell lines in terms of metastasis formation in the lung, consistent with the different in vitro growth properties. The mode of cell implantation and cell intrinsic properties strongly affected the metastatic pattern of prostate and breast cancer cell lines in mouse organs. The qPCR assay accurately determined the malignant cell burden even at early stages of metastasis progression in the lung. We describe a very sensitive assay for the highly reproducible detection and accurate quantification of human metastatic cells in mouse tissues and demonstrate its broad applicability to various experimental settings. PMID- 20364400 TI - Quantitative assessment of the effect of FGFR2 gene polymorphism on the risk of breast cancer. AB - Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent. After that, a number of studies reported that the rs2981582, rs1219648, and rs2420946 polymorphism in FGFR2 has been implicated in BC risk. However, studies on the association between these polymorphism and BC remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 46,747 cases and 87,342 controls from 16 published case-control studies was performed. Overall, significantly elevated BC risk was associated with rs2981582, rs1219648, and rs2420946 risk allele when all studies were pooled into the meta-analysis. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the subgroup analysis by ethnicity, source of controls, significantly increased risks were found for these polymorphisms in all genetic model. In conclusion, this meta-analysis suggests that rs2981582, rs1219648, and rs2420946 polymorphisms in FGFR2 are associated with elevated BC risk. PMID- 20364401 TI - Predictors of breast cancer screening behavior in women with a strong family history of the disease. AB - This study applied the self-regulation model to examine cognitive and emotional predictors of screening in unaffected women with a strong family history of breast cancer. 748 unaffected female members of an Australian registry of multiple-case breast cancer families formed the sample. Participants completed a baseline psychosocial questionnaire and a screening questionnaire 3 years later. Multinomial logistic regression was employed to determine predictors of under- and over-screening according to national guidelines. At follow-up 16% of women under-screened and 10% over-screened with mammography; 55% under-screened with clinical breast examination (CBE); and 9% over-screened with breast self examination (BSE). Of the women found screening according to guidelines for mammography 72% reported ever having received specific recommendations for mammography screening from a health professional. Compared to appropriate screeners, under-screeners on mammography were less likely to have received a screening recommendation (as were under-screeners on CBE), were younger and reported lower perceived breast cancer risk, but were at higher relative risk (RR) of breast cancer and were more likely to report elevated depression. Over screeners on mammography were more likely to be younger and have a lower RR of breast cancer. Over-screeners on BSE reported elevated cancer-specific anxiety, were less likely to be university educated and more likely to have received a recommendation for BSE. Under- and over-screening is common in women with a strong family history of breast cancer. Evaluation of interventions targeting perceived risk of breast cancer, anxiety and depression are needed to ensure women obtain accurate advice from relevant specialists and enact screening recommendations. PMID- 20364402 TI - Tuberculosis of the breast in a patient undergoing hemodialysis. AB - A 61-year-old female patient with diabetes undergoing maintenance hemodialysis presented with fever and swelling of her right breast. She had been unresponsive to nonspecific antimicrobial therapies. Breast tuberculosis and tuberculous lymphadenitis were diagnosed by excision biopsy and tissue culture. A combination antituberculous treatment including isoniazid, rifampin, ethambutol, and pyrazinamide was started and resulted in the remission of the lesions by the end of the first month of therapy. PMID- 20364403 TI - Epithelial-mesenchymal transition to be or not to be? Is the answer yes and no at the same time? PMID- 20364404 TI - Right coronary artery chronic total occlusion in presence of anomalous origin of left coronary artery. AB - Right sinus origin of left coronary artery is a very uncommon congenital coronary anomaly. The presence of an associated totally occluded right coronary artery represents an exceedingly rare picture. An accurate morphologic identification of anomalous arteries, by multi-detector computed tomography, is mandatory before planning any therapeutic intervention. We report an interesting case of chronic total occlusion of the right coronary artery in a young patient with anomalous left coronary artery. PMID- 20364405 TI - TNF-308 gene polymorphism is associated with COPD risk among Asians: meta analysis of data for 6,118 subjects. AB - Chronic obstructive pulmonary disease (COPD) is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The gene encoding tumor necrosis factor (TNF) is one of several candidate loci for the pathogenesis of COPD and is highly polymorphic. A number of studies have investigated the association between the TNF-308 polymorphisms and COPD risk in different populations, and resulted in inconsistent results. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science, and CNKI databases were searched for case-control studies published from 1966 to April 2009. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twenty-four eligible studies, comprising 2,380 COPD cases and 3,738 controls, were included in the meta analysis. The pooled result showed that the TNF-308 polymorphisms were significantly associated with an increased risk of COPD (OR=1.335, 95% CI: 1.172 1.522, for allele A carriers versus G/G; OR=1.330, 95% CI=1.174-1.505, for allele A versus allele G). Subgroup analysis supported the results in the Asian populations, but not in the Caucasian populations. When the analysis was limited to only those studies in which the COPD cases and controls were smokers/ex smokers, the pooled results supported the conclusion. This meta-analysis suggested that the TNF-308 A allele is a more significant risk factor for developing COPD among Asian populations, but not among Caucasians. PMID- 20364406 TI - Study on the association of COX-2 genetic polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu province in China. AB - To investigate the possible association of polymorphisms, cyclooxygenase-2 (COX 2) promoter region -899G>C, COX-2 codon 587G>A, with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 normal persons were collected in Hexi area of Gansu province in China. Polymorphisms of COX-2 -899G>A and COX-2 587G>A were genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin Starry staining was used. Three kinds of polymorphisms of COX-2 -899G>C were GG, GC and CC. The frequencies in gastric cancer patients were 72.9, 21.4 and 5.7%, and the frequencies in controls were 84.0, 12.8 and 3.2%, respectively. COX-2 899C carrier (GC + CC) increased risk of gastric carcinoma with an odds ratio 1.950 (95% CI: 1.067-3.586, P=0.029). The genotype of COX-2 587G>A polymorphism were GG, GA and AA. The frequencies in patients group were 86.4, 11.4 and 2.2%, and the frequencies in controls were 89.6, 9.6 and 0.8%, respectively. There was no significant difference between cases and controls in each genotype. Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in normal people (OR: 2.147, 95% CI: 1.302-3.541, P=0.003). Stratification analysis was showed that COX-2 -899C carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in healthy controls (OR: 4.000, 95% CI: 1.638-9.770). The polymorphism of COX-2 899G>C could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. COX-2 -899C carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China. However, the polymorphisms of COX 2 587G>A is no association with gastric cancer in the high incidence Hexi area of Gansu Province in China. PMID- 20364407 TI - Expression profiles of glutathione S-transferase genes in larval midgut of Bombyx mori exposed to insect hormones. AB - Glutathione S-transferases (GSTs) are believed to play a role in the detoxification of xenobiotics, resistance to insect viruses and pesticides, intracellular transport, biosynthesis of hormones and protection against oxidative stress. In this study, we used quantitative real time RT-PCR to examine expression profiles of the silkworm Bombyx mori GST-Sigma (BmGSTS2) and GST-Delta (BmGSTD2) genes in the larval midgut of the silkworm after exposure to 2 hydroxyecdysone (20E) and juvenile hormone analog (JHA). In concentration-course study, 20E at higher concentrations (1.0 and 2.0 MUg/MUl) caused significant upregulation of BmGSTD2, and all concentrations (0.5-2.0 MUg/MUl) of 20E caused significant upregulation of BmGSTS2. However, JHA in all concentrations downregulated the expression of BmGSTD2 and BmGSTS2. When exposed to either 20E (2.0 MUg/MUl) or JHA (2.0 MUg/MUl) on the third day of the fifth instar, the silkworm had higher BmGSTD2 at later time points: 15, 18, and 24 h for 20E and 24 h for JHA. BmGSTS2 expression was downregulated within 24 h after exposure to JHA and showed a time-dependent response after exposure to 20E. We also did a stage dependent study, in which JHA downregulated BmGSTD2 expression and upregulated BmGSTS2 expression significantly at both day 1 and day 3 of the fifth instar. 20E upregulated the expression of BmGSTD2 and BmGSTS2 at the two stages. These findings imply that hormones have an important role in the regulation of basal GST expression. However, further validation and field trials should be carried out on the regulatory elements relevant to BmGSTD2 and BmGSTS2 gene expression. PMID- 20364408 TI - The association of polymorphisms in DNA base excision repair genes XRCC1, OGG1 and MUTYH with the risk of childhood acute lymphoblastic leukemia. AB - The aim of this study was to evaluate the association of polymorphisms in genes encoding three key proteins of DNA base excision repair (BER): the OGG1 Ser326Cys, the MUTYH Tyr165Cys and the XRCC1 Arg399Gln with the risk of childhood acute lymphoblastic leukemia (ALL). Our study included 97 children patients with ALL (mean age 5.4+/-2.5) and 131 healthy children (mean age 6.2+/-2.8) used as controls. Genetic polymorphisms in BER pathway genes were examined using PCR and restriction fragment length polymorphism (RFLP). We have demonstrated that the OGG1 Cys/Cys genotype increases the risk of ALL (OR 5.36) whereas the Ser/Ser genotype variant strongly reduces the risk of this cancer among Polish children (OR 0.45). Although we did not observe the differences in single nucleotide polymorphisms (SNPs) in MUTYH and XRCC1 genes between control group and children with ALL, we have shown that the combined genotypes of examined genes can modulate the risk of childhood ALL in Polish population. We found that the combined genotype Arg/Gln-Cys/Cys of XRCC1/OGG1 (OR 3.83) as well as the Cys/Cys Tyr/Tyr of OGG1/MUTYH (OR 6.75) increases the risk of ALL. In contrast, the combined genotype Arg/Arg-Ser/Ser of XRCC1/OGG1 (OR 0.40) as well as the Ser/Ser Tyr/Tyr of OGG1/MUTYH (OR 0.43) played a protective role against this malignant disease. In conclusion, we suggest that polymorphisms of BER genes may be used as an important predictive factor for acute lymphoblastic leukemia in children. PMID- 20364409 TI - A haplotype in the CCR5 gene promoter was associated with the susceptibility to HIV-1 infection in a northern Chinese population. AB - It has been reported that single nucleotide polymorphisms (SNPs) in the promoter of the CCR5 gene are associated with the risk for HIV-1 infection and AIDS progression. Using resequencing, we performed a systematic survey of 78 HIV-1 seropositive individuals and 70 population-matched healthy control individuals from northern China to investigate SNPs of the CCR5 gene promoter and evaluated their effects on HIV-1 infection and the progression of AIDS. Linkage disequilibrium (LD) plots and haplotypes were generated using Haploview software. The association analyses were statistically compared using the Chi-square test with SPSS13.0 software for Windows. Seven SNPs (58755A>G, 58791C>T, 58934G>T, 59029A>G, 59353C>T, 59402A>G and 59653C>T) in the region of the CCR5 gene promoter were evaluated in this study. Among the seven SNPs, the minor allele frequencies of 58755G and 58791T were less than 2%. The differences in frequencies of the other five SNPs were not significant between case and control cohorts (P>0.05). In the case cohort, the association between these SNPs and clinical features (CD4+ T-lymphocyte counts and clinical categories) was not significant (P>0.05); however, there was a significant association between the haplotype GGTAC and susceptibility to HIV-1 infection (P<0.05), which is not consistent with other reports studied in different populations. The results suggest that the haplotype GGTAC may have a role in the process of HIV-1 infection in the northern Chinese population. PMID- 20364410 TI - Interactive bone drilling using a 2D pointing device to support Microendoscopic Discectomy planning. AB - PURPOSE: To support preoperative planning of bone drilling for Microendoscopic Discectomy, we present a set of interactive bone-drilling methods using a general 2D pointing device. METHODS: Unlike the existing methods, our framework has the following features: (1) the user can directly cut away arbitrary 3D regions on the volumetrically rendered image, (2) in order to provide a simple interface to end-users, our algorithms make 3D drilling possible through only a general purpose wheel mouse, (3) to reduce both over-drilling and unnatural drilling of an unintended region, we introduce a smart depth control to ensure the continuity of the cutting operation and (4) a GPU-based rendering scheme for high-quality shading of clipped boundaries. RESULTS: We applied our techniques to some CT data of specific patients. Several experiments confirmed that the user was able to directly drill a 3D complex region on a volumetrically rendered lumber spine through simple mouse operation. Also, our rendering scheme clearly visualizes time-varying drilled surfaces at interactive rates. By comparing simulation results to actual postoperative CT images, we confirmed the user interactively simulates similar cutting to that carried out in real surgery. CONCLUSION: We concluded our techniques perform mouse-based, direct drilling of complex 3D regions with high-quality rendering of drilled boundaries and contribute to preoperative planning of Microendoscopic Discectomy. PMID- 20364411 TI - Editorial: sepsis. PMID- 20364412 TI - Update on the role of Toll-like receptors during bacterial infections and sepsis. AB - Toll-like receptors (TLRs) are recognition molecules that importantly contribute to the innate immune response to bacterial and viral infections. Once TLRs sense the presence of invading pathogens a signal transduction cascade is initiated that eventually leads to the production of pro-inflammatory mediators and attraction of neutrophils to the site of infection. While the ultimate goal of this defense pathway is the successful elimination of invading microbes, prolonged or exaggerated stimulation of TLR-associated events can lead to systemic inflammation and clinical symptoms of sepsis. This brief review summarizes the impact of selected TLRs in the host response to clinically important bacteria and provides insights into TLR-associated therapeutic approaches during sepsis and inflammation. PMID- 20364413 TI - The vagal immune reflex: a blessing from above. AB - The innate immune response is activated upon recognition of infection or injury. A tight regulation of this inflammatory response is vital to ensure that it does not spin out of control and becomes harmful to the host. Recently, a neural circuit has been identified that controls the inflammatory response in a reflex like manner. This circuit involves the vagus nerve which is able to sense inflammation and to respond to it by releasing acetylcholine which, through an interaction with immune cells, dampens the inflammatory response. The current knowledge regarding this "vagal immune reflex" is discussed with an emphasis on its role in sepsis. PMID- 20364414 TI - Mitochondrial function and dysfunction in sepsis. AB - Mitochondria are the key source of cellular ATP and their structure and function are markedly affected by pathophysiologic processes associated with the host's response to invading pathogens. In particular, the highly reactive compound peroxynitrite, generated by the reaction of nitric oxide and superoxide anions, inhibits mitochondrial enzymes and damages lipids, proteins, and nucleic acids. Enhanced oxidative stress induces DNA strand breaks that are repaired by activation of poly(ADP-ribose)polymerase (PARP). This process consumes large amounts of nicotinamide adenine dinucleotide (NAD(+)) leading to cellular NAD(+) depletion that impairs flux of reducing equivalents into the respiratory chain and also further promotes inflammation. In experimental studies, novel therapeutic strategies that aim to ameliorate the host's pathogen response or to modulate intracellular signaling events related to oxidative stress protected mitochondrial function and preserved cellular respiration ultimately leading to improved organ function. PMID- 20364415 TI - Mortality, morbidity and special issues of obese ICU patients. AB - Obesity is on the advance in western industrialised countries and is therefore increasingly relevant also to intensive care medicine. In contrast to the common prejudice that obese patients probably have a higher ICU mortality than lean patients, convincing meta-analyses have revealed that this is not the case. Nevertheless, obese ICU patients are challenging. Especially mechanic ventilation has to be addressed: besides obesity-related anatomical problems that may complicate intubation, obstructive sleep apnoea, obesity hypoventilation syndrome and increased intra-abdominal pressure are of major relevance concerning ventilation, weaning and successful extubation. Also the risk of infections is increased in obese ICU patients, although this does not seem to increase the risk of sepsis. Nevertheless, the interplay of obesity and sepsis is a fascinating field in that adipous tissue is not just a passive reservoir of energy but an active endocrine and immunomodulating organ. However, the way of how adipokines interact with inflammation and coagulation in sepsis has yet to be clarified. PMID- 20364416 TI - Blood coagulation disorders in septic patients. AB - Host defense and blood coagulation are tightly connected and interacting systems, necessary for the integrity of an organism. Complex mechanisms regulate the intensity of a host response to invading pathogens or other potentially dangerous situations. Under regular conditions, this response is limited in time and located to the site of injury. Sometimes, however, systemic host response is overwhelming and disproportional and causes damage, not cure. Dependent on the genetical predisposition of the host, its current immunocompetence, or the type of injury, the reaction leads to the clinical picture of the different degrees of sepsis. Septic organ dysfunction is caused by intravascular fibrin deposition as a result of coagulation activation, anticoagulant breakdown, and shut down of fibrinolysis. This article describes the major pathophysiologic reactions in these situations and presents www.SepDIC.eu, an online tool on sepsis and associated coagulopathy. PMID- 20364417 TI - [De-novo generation of vascularized tissue using different configurations of vascular pedicles in perforated and closed chambers]. AB - Growing three-dimensional tissue within a chamber requires vigorous angiogenesis initiated by, for example, an arteriovenous fistula or a ligated vascular pedicle. Growth may also be enhanced by contact with the external environment. In this study tissue growth in a rat model, vascularized via an arteriovenous loop (AV Loop) or ligated pedicle, was compared in chambers that were either closed or perforated. Chambers were harvested at 4 weeks and tissue volume and histology compared. In perforated chambers, more tissue were generated using the ligated pedicle (0.75 ml+/-0.04) than the AV Loop (0.59 ml+/-0.01). Perforated chambers generated larger volumes of tissue than closed chambers because they encouraged tissue ingrowth through the perforations. Both vessel configurations supported tissue growth but, interestingly, the ligated pedicle resulted in significantly more tissue in the perforated chambers. PMID- 20364418 TI - Rokitansky's diseases and cause of death : A short pathological and historical discourse. AB - Carl Rokitansky was one of the foremost experts and pioneers in pathological anatomy of the 19th century. Virchow and Rokitansky paved the way for the modern specialty of pathology, as we know it today. Whilst Virchow was the doyen of histopathology, Rokitansky's merit was his excellent gross pathology establishing thereby a nosological classification of disease. For this achievement, Virchow called Rokitansky the Linee of pathology. In spite of his importance little is reported on Rokitansky. If the cause of death is mentioned, it is always stated incorrectly. This error may be due to a misleading certificate of death, which was issued without autopsy. This essay aims to describe Rokitansky's illnesses, particularly in his last months, and to deduce from available evidence the most probable cause of his death - with short explanations for non-medical readers. Briefly, Rokitansky suffered from arteriosclerosis leading to stenocardial attacks (angina pectoris). Rokitansky tried to relieve himself from pain by using chloroform. His personal description of the symptoms in his autobiography and the circumstances of his death clearly indicate a heart attack as the cause of death. PMID- 20364419 TI - Etiopathogenesis of neurogenic pulmonary edema. AB - This comment focus on new findings in etiopathogenesis of neurogenic pulmonary edema. It highlights the importance of understanding of pathophysiology as well as proper diagnosis of this clinical entity. PMID- 20364427 TI - Pharmacokinetics in mice and metabolism in murine and human liver fractions of the putative cancer chemopreventive agents 3',4',5',5,7-pentamethoxyflavone and tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone). AB - PURPOSE: The flavones tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) and 3',4',5',5,7-pentamethoxyflavone (PMF) are under development as potential colorectal cancer chemopreventive agents as they reduced adenoma development in the Apc(Min) mouse model of intestinal carcinogenesis. Here, the pharmacokinetic properties and metabolism of these flavones after oral administration were compared in mice. METHODS: C57BL/6 J mice received an oral bolus of PMF or tricin (807 MUmol/kg). Parent flavone and metabolites were analyzed by HPLC/UV in plasma, liver and gastrointestinal tissues. Flavones were incubated with mouse or human hepatic microsomes or 9000xg supernatant (S9), both fortified with a NADPH generating system and either uridine 5'-diphosphoglucuronic acid (UDPGA, microsomes) or 3'-phosphoadenosine-5'-phosphosulfate (PAPS, S9). Disappearance of substrate was assessed by HPLC/UV, metabolites were characterized by HPLC/MS/MS. RESULTS: Plasma concentrations and area under the plasma concentration versus time curve for PMF were higher than those for tricin. A mono-O-desmethyl PMF and several isomeric mono-O-desmethyl PMF glucuronides and sulfonates were major PMF metabolites in murine plasma, liver and intestinal tissue. In murine and human liver fractions, in vitro metabolic removal of tricin was faster than that of PMF. On kinetic analysis of metabolite generation in these incubations, apparent maximal velocity (V(max)) values for the generation of tricin O-glucuronide or O sulfonate were consistently several fold higher than those characterizing the production of mono-O-desmethyl PMF glucuronides or sulfonates via the intermediacy of O-desmethyl PMF. CONCLUSIONS: The results suggest that inclusion of methoxy moieties confers metabolic stability onto the flavone scaffold. PMID- 20364428 TI - Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer. AB - PURPOSE: To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were naive to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status. RESULTS: Overall median TTP was 6.4 months (95% CI [2.7-11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80-100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8 17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80-100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80-100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopenia, and abdominal pain, and most were of grades 1 2 severity. CONCLUSIONS: The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial. PMID- 20364429 TI - Fractures in proximal spinal muscular atrophy. AB - INTRODUCTION: Fractures are a common problem for patients with spinal muscular atrophy (SMA). PATIENTS: A total of 131 patients with proximal SMA with an average age of 13.2 +/- 9.2 years (0.7-65.6) were evaluated retrospectively. In 60 patients 94 different fractures were observed. The group consisted of 11 patients with type Ib, 81 with type II, 33 with type IIIa, 4 with IIIb and 2 with type IV. 38 of 81 SMA II patients and 17 of 33 SMA IIIa patients had suffered fractures at an average age of 8.3 +/- 5.3 years (0.0-25.1) (SMA II) and 9.3 +/- 6.0 years (0.0-22.1) (SMA IIIa). RESULTS: The most frequent fractures were of the femur (50), usually distal, of the lower leg and ankle (15), and upper arm (9). The distribution of fractures was different in SMA II and SMA IIIa. Most of the fractures could be treated conservatively. Only two femoral shaft fractures, one upper arm and a lower arm fracture were treated surgically by osteosynthesis. CONCLUSION: Competent fracture treatment is an important part of the orthopaedic care of SMA patients. PMID- 20364430 TI - Is upper extremity trauma an independent risk factor for lower extremity venous thromboembolism? An 11-year experience at a Level I trauma center. AB - INTRODUCTION: Venous thromboembolism (VTE) is an important problem in orthopedic trauma patients. An association between VTE and upper extremity injury has not been reported. The purpose of this investigation was to determine whether upper extremity trauma is an independent risk factor for lower extremity VTE. This study also attempted to identify associations between VTEs and demographic and injury variables in patients that sustained upper extremity trauma. METHODS: Eleven years of data from the trauma registry at our Level I trauma center was retrospectively reviewed in an injury-matched cohort study. From an initial pool of 646 patients who sustained upper extremity trauma, 32 subjects (4.95%) were identified as having major upper extremity injuries as well as thromboembolic complications. Thirty-two injury-matched controls were randomly selected from the 646 patients with major upper extremity injuries. Regression analysis was performed to determine variables that were significantly associated with lower extremity thromboembolic complications. RESULTS: Overall incidence of VTE in patients sustaining upper extremity injury was 4.95% (deep vein thrombus 4.64%, pulmonary embolism 0.31%) and was similar to the 4.95% VTE rate in patients without upper extremity injury. Major head injury (p = 0.022) occurred at increased frequency in the VTE group. Patients with increased length of hospital stay (p < 0.001) and length of time on a ventilator (p = 0.002) were at significantly higher risk for thromboembolic complications. No patient with isolated upper extremity trauma had complications from VTE. CONCLUSION: Lower extremity VTE occurs at similar rates in patients sustaining upper extremity injury compared to those patients that do not. Major upper extremity orthopedic trauma is not an independent risk factor for lower extremity VTE, and current clinical management guidelines for VTE prophylaxis are adequate for patients sustaining major upper extremity trauma. PMID- 20364431 TI - Principal transcriptional regulation and genome-wide system interactions of the Asp-family and aromatic amino acid networks of amino acid metabolism in plants. AB - Amino acid metabolism is among the most important and best recognized networks within biological systems. In plants, amino acids serve multiple functions associated with growth. Besides their function in protein synthesis, the amino acids are also catabolized into energy-associated metabolites as well we into numerous secondary metabolites, which are essential for plant growth and response to various stresses. Despite the central importance of amino acids in plants growth, elucidation of the regulation of amino acid metabolism within the context of the entire system, particularly transcriptional regulation, is still in its infancy. The different amino acids are synthesized by a number of distinct metabolic networks, which are expected to possess regulatory cross interactions between them for proper coordination of their interactive functions, such as incorporation into proteins. Yet, individual amino acid metabolic networks are also expected to differentially cross interact with various genome-wide gene expression programs and metabolic networks, in respect to their functions as precursors for various metabolites with distinct functions. In the present review, we discuss our recent genomics, metabolic and bioinformatics studies, which were aimed at addressing these questions, focusing mainly on the Asp-family metabolic network as the main example and also comparing it to the aromatic amino acids metabolic network as a second example (Angelovici et al. in Plant Physiol 151:2058-2072, 2009; Less and Galili in BMC Syst Biol 3:14, 2009; Tzin et al. in Plant J 60:156-167, 2009). Our focus on these two networks is because of the followings: (i) both networks are central to plant metabolism and growth and are also precursors for a wide range of primary and secondary metabolites that are indispensable to plant growth; (ii) the amino acids produced by these two networks are also essential to the nutrition and health of human and farm animals; and (iii) both networks contain branched pathways requiring extensive regulation of fluxes between the different branches. Additional views on the biochemistry, regulation and functional significance of the Asp-family and aromatic amino acid networks and some of their associated metabolites that are discussed in the present report, as well as the nutritional importance of Lys and Trp to human and farm animals, and attempts to improve Lys level in crop plants, can be obtained from the following reviews as examples (Radwanski and Last in Plant Cell 7:921-934, 1995; Halkier and Gershenzon in Annu Rev Plant Biol 57:303 333, 2006; Ufaz and Galili in Plant Physiol 147:954-961, 2008; Jander and Joshi in Mol Plant 3:54-65, 2010). PMID- 20364432 TI - Pneumatic retinopexy for the management of impending macular hole: an optical coherence tomography study. AB - The intravitreal injection of an expansile gas bubble can relieve vitreofoveal traction and be used as an outpatient-based procedure for impending macular hole. We present a case in which this procedure was successfully employed and demonstrated with spectral domain optical coherence tomography (OCT) imaging. PMID- 20364433 TI - Bovine lactoferrin interacts with cable pili of Burkholderia cenocepacia. AB - In this study we evaluated the ability of lactoferrin, the most abundant antimicrobial protein in airway secretions, to bind the surface structures of a Burkholderia strain cystic fibrosis-isolated. Burkholderia cenocepacia is a gram negative bacterium involved as respiratory pathogen in cystic fibrosis patient infections. This bacterium possesses filamentous structures, named cable pili that have been proposed as virulence factors because of their ability to bind to respiratory epithelia and mucin. Previously, we demonstrated that bovine lactoferrin was able to influence the efficiency of invasion of different iron regulated morphological forms of B. cenocepacia. Bovine lactoferrin showed to efficiently inhibit invasion of alveolar epithelial cells by free-living bacteria or iron-induced aggregates or biofilm. Results of the present study demonstrate that bovine lactoferrin is also able to specifically bind to B. cenocepacia cells and show that cable pili are involved in this interaction. The attachment of bovine lactoferrin to pili led to a reduced binding of bacterial cells to mucin. Since cable pili are implicated in mediating the bacterial interactions with mucin and epithelial cells, lactoferrin binding to these structures could play an important role in neutralizing bacterial infection in cystic fibrosis patients. PMID- 20364434 TI - Connecting mean field models of neural activity to EEG and fMRI data. AB - Progress in functional neuroimaging of the brain increasingly relies on the integration of data from complementary imaging modalities in order to improve spatiotemporal resolution and interpretability. However, the usefulness of merely statistical combinations is limited, since neural signal sources differ between modalities and are related non-trivially. We demonstrate here that a mean field model of brain activity can simultaneously predict EEG and fMRI BOLD with proper signal generation and expression. Simulations are shown using a realistic head model based on structural MRI, which includes both dense short-range background connectivity and long-range specific connectivity between brain regions. The distribution of modeled neural masses is comparable to the spatial resolution of fMRI BOLD, and the temporal resolution of the modeled dynamics, importantly including activity conduction, matches the fastest known EEG phenomena. The creation of a cortical mean field model with anatomically sound geometry, extensive connectivity, and proper signal expression is an important first step towards the model-based integration of multimodal neuroimages. PMID- 20364435 TI - Harsh discipline, childhood sexual assault, and MAOA genotype: an investigation of main and interactive effects on diverse clinical externalizing outcomes. AB - We studied the impact of MAOA genotype, childhood sexual assault, and harsh discipline on clinical externalizing symptoms (substance problems, adult antisocial behavior, and conduct disorder). Participants were 841 individual twins from the Minnesota Twin Family Study assessed through age 25. MAOA genotype was not associated with differences in any phenotype, nor was there a significant interaction between MAOA and harsh discipline for any phenotype or a significant interaction between MAOA and childhood sexual assault for substance problems. We found evidence that childhood sexual assault interacted with MAOA genotype to predict antisocial behavior and conduct disorder symptoms. Individuals with the low MAOA activity genotype who reported childhood sexual assault had more symptoms than individuals with either the high MAOA activity genotype and/or no history of childhood sexual assault. These findings suggest that the previously reported interaction between MAOA and childhood maltreatment may be specific to the antisocial subset of externalizing disorders. PMID- 20364436 TI - Behavioral differences between C57BL/6J x FVB/NJ and C57BL/6J x NZB/B1NJ F1 hybrid mice: relation to control of ethanol intake. AB - C57BL/6J x FVB/NJ F1 (B6 x FVB) mice consume more alcohol than C57BL/6J x NZB/B1NJ F1 (B6 x NZB) mice and this high alcohol consumption is stable after abstinence whereas B6 x NZB show reduced consumption, thus providing models of Sustained Alcohol Preference (SAP) and Reduced Alcohol Preference (RAP). In female hybrids, we assessed several behavioral responses to define behaviors which might predict SAP and RAP. B6 x FVB exhibited less severe ethanol-induced conditioned taste aversion and were less sensitive to ethanol-induced loss of righting reflex than B6 x NZB. Both hybrids demonstrated ethanol-induced place preference and a low ethanol withdrawal severity. We found that these hybrids differ in their sensitivity to the aversive and sedative, but not rewarding, effects of ethanol. Results of elevated plus maze, mirror chamber, and locomotor tests reveal B6 x FVB mice are less anxious and more active than B6 x NZB mice. Results obtained offer insights about factors that determine SAP and RAP in these new genetic models of alcohol consumption. PMID- 20364437 TI - Highly effective treatment with tacrolimus ointment in an adolescent with oral graft-versus-host disease. AB - CASE: We report a case of acute oral graft-versus-host disease in an adolescent, which was successfully treated with tacrolimus 0.1% ointment. CONCLUSION: Although tacrolimus ointment is not licensed for the indication of oral GvHD, this case report provides preliminary evidence for a potential effectiveness of using tacrolimus in case of failure when GvHD is resistant. PMID- 20364439 TI - Distortion of anterior airway anatomy during laryngoscopy with the GlideScope videolaryngoscope. AB - PURPOSE: A non-line-of-sight view is expected to cause less movement of the anterior airway anatomy and cervical spine during laryngeal visualization. Reduced distortion of anterior airway anatomy during laryngoscopy with the GlideScope videolaryngoscope (GVL), compared with the Macintosh laryngoscope, could explain the relatively easier nasotracheal intubation with the GVL. The purpose of this radiographic study was to compare the degree of anterior airway distortion and cervical spine movement during laryngoscopy with the GVL and the conventional Macintosh laryngoscope. METHODS: Twenty patients requiring general anesthesia and tracheal intubation were studied. Each patient underwent laryngoscopy using the first-generation GVL and a direct laryngoscope with a Macintosh blade. During each laryngoscopy, a radiograph was taken when the best view of the larynx was obtained. Independent radiologists with subspeciality training in musculoskeletal imaging evaluated anterior airway distortion and cervical spine movement. RESULTS: The distance between the epiglottis and the posterior pharyngeal wall during the GlideScope procedure was 21% less than that during the Macintosh laryngoscopy (P < 0.05). Anterior deviations of the vertebral bodies from baseline were 27, 32, 36, and 39% less at the atlas, C2, C3, and C4 vertebrae, respectively, during the GlideScope procedure than those measured during Macintosh laryngoscopy (P < 0.01). Cervical extension between the occiput and C4 during the GlideScope procedure was 23% less than that during Macintosh laryngoscopy (P < 0.05). CONCLUSION: Both anterior airway distortion and cervical spine movement during laryngeal visualization were less with the GVL than with the Macintosh laryngoscope. PMID- 20364438 TI - Docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-6) algal oils reduce inflammatory mediators in human peripheral mononuclear cells in vitro and paw edema in vivo. AB - The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA. In addition, DPAn-6 decreased intracellular levels of cyclooxygenase-2 (COX-2) and was a potent inhibitor of pro-inflammatory prostaglandin E2 (PGE2) production. DHA/DPAn 6-rich DHA-S (DHA-S) algal oil was more effective at reducing edema in rats than DHA-rich DHA-T (DHA-T), suggesting that DPAn-6 has anti-inflammatory properties. Further in vivo analyses demonstrated that feeding DPAn-6 alone, provided as an ethyl ester, reduced paw edema to an extent approaching that of indomethacin and enhanced the anti-inflammatory activity of DHA when given in combination. Together, these results demonstrate that DPAn-6 has anti-inflammatory activity and enhances the effect of DHA in vitro and in vivo. Thus, DHA-S algal oil may have potential for use in anti-inflammatory applications. PMID- 20364440 TI - Metabolization of [Ru(eta(6)-C (6)H (5)CF (3))(pta)Cl (2)]: a cytotoxic RAPTA type complex with a strongly electron withdrawing arene ligand. AB - The anticancer ruthenium-arene compound [Ru(eta(6)-C(6)H(5)CF(3))(pta)Cl(2)] (where pta is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane), termed RAPTA-CF3, with the electron-withdrawing alpha,alpha,alpha-trifluorotoluene ligand, is one of the most cytotoxic RAPTA compounds known. To rationalize the high observed cytotoxicity, the hydrolysis of RAPTA-CF3 in water and brine (100 mM sodium chloride) and its reactions with the protein ubiquitin and a double-stranded oligonucleotide (5'-GTATTGGCACGTA-3') were studied using NMR spectroscopy, high resolution Fourier transform ion cyclotron resonance mass spectrometry, and gel electrophoresis. The aquation of the ruthenium-chlorido complex was accompanied by a loss of the arene ligand, independent of the chloride concentration, which is a special property of the compound not observed for other ruthenium-arene complexes with relatively stable ruthenium-arene bonds. Accordingly, the mass spectra of the biomolecule reaction mixtures contained mostly [Ru(pta)] biomolecule adducts, whereas [Ru(pta)(arene)] adducts typical of other RAPTA compounds were not observed in the protein or DNA binding studies. Gel electrophoresis experiments revealed a significant degree of decomposition of the oligonucleotide, which was more pronounced in the case of RAPTA-CF3 compared with RAPTA-C. Consequently, facile arene loss appears to be responsible for the increased cytotoxicity of RAPTA-CF3. PMID- 20364441 TI - Endosperm development in the Araceae (Alismatales) and evolution of developmental modes in monocots. AB - The Araceae, a basal-most family of Alismatales that basally diverged subsequent to Acorales in monocot phylogeny, are known to have diverse modes of endosperm development: nuclear, helobial, and cellular. However, the occurrence of nuclear and helobial endosperm development has long been debated. Here, we report a (re )investigation of endosperm development in Lysichiton, Orontium, and Symplocarpus of the Orontioideae (a basal Araceae), in which nuclear endosperm development was recorded more than 100 years ago. The results show that all three genera exhibit a cellular, rather than nuclear, endosperm development and suggest that the helobial endosperm development reported as an "unmistakable record" from Ariopsis is likely cellular. Thus the Araceae are very likely characterized by cellular endosperm development alone. An extensive comparison with other monocots in light of phylogenetic relationships demonstrates that a plesiomorphic cellular endosperm development is restricted to the three basal monocot orders Acorales, Alismatales, and Petrosaviales, in which evolutionary changes from cellular to nuclear endosperm development occurred twice as major events, once within Alismatales and once as a synapomorphy of the eight remaining monocot orders, including Dioscoreales, Liliales, Asparagales, and Poales, and that helobial endosperm development, which is known for many monocot families, evolved as homoplasy throughout the monocots. PMID- 20364442 TI - 'These days virginity is just a feeling': heterosexuality and change in young urban Vietnamese men. AB - This paper argues that young Vietnamese men's beliefs around women's changing sexual identities and habits generate some anxiety around their own heterosexual abilities, while contributing to growing doubts around 'traditional' masculine advantage within sexual relations. It explores this notion in regard to eight Vietnamese men aged 18-30 years, interviewed over 13 months of fieldwork in Hanoi, Vietnam. The paper suggests that young men are increasingly ambivalent about notions of 'gendered morality' in general and the significance of female virginity in particular, because of popular ideas around women's changing sexual behaviours since the economic liberalisation of Vietnam in the late 1980s. However, while such ambivalence might at first suggest a shift toward improved gender and sexual equality, findings reveal that some young urban Vietnamese men construct and reinforce explicitly 'masculinist' gender ideologies by watching heterosexual pornography in groups with male friends or by visiting female sex workers for the purpose of watching their friends have sex. In a time of rapid change around discourses on women, some young men seek to build a stable community and relationships with each other by controlling the terms and practice by which women's bodies are used and consumed. PMID- 20364443 TI - Between stigmatisation and regulation: prostitution in colonial Northern Vietnam. AB - Colonisation was a masculine adventure which took place in a distorted world full of 'welcoming' native women. The colonial encounter therefore was both racial and gendered: boundaries between European men and Vietnamese women were obvious. On the other hand the intimacy that resulted from this encounter blurred the racial boundaries that were the foundation of the colonial order. These boundaries had to be redrawn or sharpened. Focusing on French colonial northern Vietnam (Tonkin) this paper examines how the whole colonial encounter was embodied in the sexual encounter between European men and native women and how prostitution was an integral part of the colonial order. This analysis of the regulation of prostitution and its ambivalence reveals that the definition of prostitution and its treatment by the French colonial authorities was political, racial and therefore connected to a specific period. The political definition of prostitution in today's Vietnam is different from the colonial one. This shift reveals that prostitution is a pertinent vantage point from which one can study how a society apprehends itself and its own future. PMID- 20364445 TI - The use of dental wire to facilitate tendon passing through the pulley mechanism. PMID- 20364446 TI - A novel technique for biliary T-tube fixation. PMID- 20364447 TI - Safe and re-usable splinting for hand surgery. PMID- 20364448 TI - A new method to pass an intramedullary cable through bones using a guide suture. PMID- 20364449 TI - Easy insertion of the gamma nail's end cap. PMID- 20364451 TI - Improvised straight needle suture passer. PMID- 20364450 TI - Pulsed lavage in the orthopaedic theatre. PMID- 20364452 TI - Proceedings from the International Workshop on Computational Systems Biology Approaches to Analysis of Genome Complexity and Regulatory Gene Networks, Singapore, 20-25 November 2008. PMID- 20364453 TI - Mental Dysfunction in Parkinson's Disease. Proceedings of the 9th International Congress on Mental Dysfunction and other Non-Motor Features in Parkinson's Disease and Related Disorders, Dresden, Germany, 16-19 October 2008. PMID- 20364454 TI - Transplant tourism. AB - PURPOSE OF REVIEW: Because of the ongoing organ donor shortage, transplant tourism is occurring at an increasing rate both in the USA and abroad. To date, there have been little published data to help guide the programmatic philosophy of the USA transplant centers regarding transplant tourism. RECENT FINDINGS: We summarize position statements from several transplant societies regarding transplant tourism and specifically transplantation occurring in China (because of the use of executed prisoners as organ donors). Transplant tourism is ever increasing and patients may be at risk for greater post-transplant morbidity as well as inadequate follow up care. Transplant centers require some guidance with regard of how to deal with these patients. SUMMARY: Transplant tourism is an increasing reality facing the USA transplant centers. Most professional societies do not condone it yet cannot abrogate a physician's right to care for such patients. Ethical principles mandate transplant physicians provide adequate care for returning transplant tourists. Better ways of assessing the scope of the problem are necessary. Transplant tourism may exist because of the disparity between the need for organ donors and their availability and is thus is likely to continue into the future. PMID- 20364455 TI - Proceedings from the 7th International Symposium on Advanced Ovarian Cancer. PMID- 20364456 TI - MMP12, lung function, and COPD in high-risk populations. PMID- 20364457 TI - Sensitive cardiac troponin T assay. PMID- 20364458 TI - Discharge planning and rates of readmissions. PMID- 20364459 TI - Discharge planning and rates of readmissions. PMID- 20364460 TI - Molecular basis of colorectal cancer. PMID- 20364462 TI - Steric and electronic effects in metallophilic double salts. AB - This Perspective highlights our efforts to assemble infinite chains of metal atoms in double salts of the form [M](+)[M](-) under the complementary influences of metallophilic interactions and electrostatic attraction. Our design strategy necessarily incorporates the significant steric constraints of one-dimensional assemblies as well as the more subtle and challenging electronic tuning of weak dispersion forces. PMID- 20364461 TI - Molecular basis of colorectal cancer. PMID- 20364463 TI - Planar-chiral imidazole-based phosphine ligands derived from [2.2]paracyclophane. AB - Two planar chiral heteroaryl monophosphines have been synthesised and studied. The phosphines are readily prepared from 4-imidazole[2.2]paracyclophane by selective deprotonation and reaction with the appropriate dialkylchlorophosphines. The planar chiral imidazole was constructed in four steps from readily available [2.2]paracyclophane. The 2-phosphino-N [2.2]paracyclophanes were active in the Suzuki-Miyaura coupling of aryl bromides and chlorides. Coordination studies indicate P,N-chelation in the solid-state. These studies lay the foundations for asymmetric couplings. PMID- 20364466 TI - Nurses misunderstand GBS patients needs. PMID- 20364469 TI - [Human factor in concern to occupational safety]. AB - The article deals with results of studies covering safety problems in connection with human factor. The authors presented risks and their sources classification, models of risky behavior exemplified by actual and potential workers. PMID- 20364470 TI - [Improving the system of methods covering clinical and rentgenologic observation over workers exposed to dust aerosol]. AB - The article deals with analysis of clinical and rentgenologic changes in various pneumoconiosis types over 1960 to 2007 in Novosibirsk region. Findings are that analogous plain film fails to diagnose pulmonary pneumoconiosis. Pneumoconioses associated with "minimal" dust invasions in 10-15% of cases are not revealed by plain films. PMID- 20364471 TI - [Biochemical and hemocoagulation criteria for evaluating the risk of nephropathy development in workers with occupational exposure to dust]. AB - The authors present main mechanisms and leading pathogenetic factors underlying occupationally mediated dust nephropathies. The article covers results of analysis concerning biochemical and hemocoagulation criteria to evaluate the risk of nephropathy in workers exposed to high concentrations of industrial dust aerosols. PMID- 20364472 TI - [The landscape-biocenological concept of a combination of natural foci of diseases. Environmental conditions predetermining the formation of biotic and epizootic bases for a combination of natural foci of diseases]. AB - The potential of a combination of foci of diseases is not limited by environmental conditions. The biotic and epizootic bases for the combination of foci are formed under the influence of the environmental factors predetermining the formation of the bases for the combination of the foci. These are pathogen populations, parasitic systems of foci with forming parasitocenoses, the functional and spatial pattern of the foci, susceptibility of hosts (vectors), polyhostality of pathogens and mechanisms of their transmission. The author places emphasis on the fact that any single factor cannot serve as a basis for the combination of the foci since the combination bases form only when pairs of identical factors interact. He points to the interrelation and correlation of the considered bases for the combination of the foci. The combination of invasion foci is noted to be effected in the absence of mixed infectiousness of specimens. The coacting parasitic systems of foci are predetermined to manifest themselves as the underlying biotic bases that determines the type of the combination of foci. The level of the combination of parasitic systems of the foci is predetermined by the parasitocenoses of coacting populations of pathogens and hosts (parasitic systems). The interacting functional and spatial patterns of the foci predetermine the latter's community, by acting as biotic bases for the combination. The susceptibility of hosts (vectors) and the polyhostality predetermine a range of interacting parasitic systems. The polymorphism of the types of hosts determines the functional strength of parasitic systems, by predetermining the stability of a combination of foci. The interacting identical mechanisms of transmission act as an epizootic basis for the combination of the foci. The continuity of the biotic and epizootic bases for the combination of the foci is stated. PMID- 20364473 TI - [Monitoring of the malaria situation and the assessment of antimalaria measures in the Republic of Uzbekistan]. AB - In 2008, the major malaria vectors An.superpictus and An. pulcherrimus amounted up to 50 specimens per premise in the Surkhandaryinsk and Kashkadaryinsk Regions. The high density of larvae in the water reservoirs (as many as 30-50 specimens per square meter) and rice fields (8-60 specimens per square meter) was noted in the Surkhandaryinsk, Namangan, Ferghana, and Tashkent Regions. There is a high susceptibility of the territory due to increased migration between Uzbekistan, Kyrgyzstan, and Tajikistan. In 2008, a total of 4,958,685 subjects passed through 68 border checkpoints, among them there were 835 (0.02%) individuals with suspected infectious diseases, including malaria. The foci of irrigation-ditch area and their conjugate foci of the floodplain-river one of the Surkhandaryinsk Region are most dangerous. Analysis of the trend of malaria foci showed a reduction in the number of new active foci from 44 in 2006 to 6 to 2008. The increased number of residual inactive and sanitized foci suggests that the malaria situation has considerably improved. PMID- 20364474 TI - [The epidemic manifestations of leptospirosis in the Ulyanovsk region]. PMID- 20364475 TI - [Role of chromosomal rearrangement and conservative chromosome sites in amniote evolution]. AB - Specific features of evolution of chromosomes in mammals and other amniotes are reviewed. Comparative analysis of chromosome architecture revealed nonrandom distribution of chromosome rearrangement sites in genome, probable role of chromosome rearrangement in adaptation, and evolution-mediated selection of conservative chromosome sites. The chromosome sites stable during evolution are saturated with genes contributing to early organism development. Ruptures of these sites are incompatible with organism survival. Further analysis of chromosome evolution requires more information about completely sequenced genomes. PMID- 20364476 TI - [Variability of the INV gene fragment encoding a functionally important domain of Yersinia pseudotuberculosis invasin]. AB - A total of 84 Y. pseudotuberculosis isolates were studied. The isolates were obtained in Russian Federation in 1967-2008. The majority of Y. pseudotuberculosis isolates (n = 55) were of clinical origin and were isolated from feces of patients with the clinically and serologically proved diagnosis of pseudotuberculosis/Far East scarlet-like fever. These isolates included 18 isolates obtained from 3 outbreaks. Nine isolates were isolated from the internal organs of wild rodents. Other isolates were obtained from environmental sources. Ten Y. pseudotuberculosis isolates belonged to the serovar III and the other isolates belonged to the serovar I. The sequences of 600 b.p. fragment of the inv gene that encodes 667 through 866 invasin amino acids were determined for all isolates. Totally, 3 allelic variants were found. The most abundant allele 1 was found in 76 isolates. The allele 1 is represented in the database Genbank by the strain IP31758 isolated in the Far East of Russia (Eppinger et al., 2007). The allele 2 differed from allele 1 in 3 positions: G,2299N, O2300N, and O2302N. Substitutions in positions 2299 and 2302 were non-synonymous and resulted in amino acid substitutions Ser768 Thr and Val769 Ala. Six isolates carried allele 2. Allele 3 was found in two isolates different from allele 2 by a synonymous substitution G2324O. This allele is similar to the sequence found in Y. pestis strains, represented in the GenBank. The allelic distribution was not serovar specific: Y. pseudotuberculosis of serovar III and majority of serovar I isolates carried allele 1. The analysis of the allelic distribution among subpopulations formed on the base of a source of isolation revealed a statistically significant difference in spreading of alleles among clinical and wild rodent isolates (p < 0.05). Allele 1 prevailed over clinical isolates (95%), while allele 1 and allele 2 were disseminated equally among rodent isolates (55 % and 45 %, respectively). PMID- 20364477 TI - [Genotyping some Borrelia burgdorferi sensu lato isolates from Ixodes ricinus ticks in Russia and Ukraine]. AB - The 4 Borrelia burgdorferi sensu lato isolates obtained from 1. Ricinus ticks collected in the natural foci in Russia and Ukraine, having an unusual RFLP Msel pattern, were studied using sequencing rrfA-rrlB spacer and rrs gene. The Ir-5215 isolate from the tick collected in southern Ukraine represented recently described genospecies B. spielmanii pathogenic for humans. The three atypical isolates Ir-3519, Ir-4721, and Ir-4812 had 100% identity with the sequence of the atypical European B. burgdorferi sensu stricto strains. They constituted a subgroup of the B. burgdorferi sensu stricto on the grounds of Multilocus sequence analysis (MLSA). These data can be indicative of the genetic heterogeneity of the current group B. burgdorferi sensu stricto. PMID- 20364478 TI - [Molecular-genetic analysis of the Batai virus strains isolated from mosquitoes in Volgograd Region of the Russian Federation, West Ukraine, and Czech Republic]. AB - Partial nucleotide sequence of the M-segment from five Batai virus strains was determined. These strains were isolated in Volgograd Region, West Ukraine, and Czech Republic. Our data based on the partial sequence of the M-segment of Batai virus strains demonstrated that the strains isolated in Russian Federation, Ukraine, and Czech Republic grouped together into an European genetic group that was distinct from Asian and African strains of Batai virus. PMID- 20364479 TI - Proceedings from Conversations in the Capital District: a Conference about Hormones, Albany, New York, October 23-24, 2008. PMID- 20364480 TI - Proceedings from the Materials for Biomedical Applications Symposium - IUMRS-ICAM 2007, Bangalore, India. PMID- 20364481 TI - 2009 growth in Medicaid enrollment sets record. PMID- 20364482 TI - Timing and rate of nitrogen application influence grain quality and yield in maize planted at high and low densities. AB - BACKGROUND: Efficient use of nitrogen (N) is considered one of the most important inputs needed for increasing grain quality and crop productivity. Hypothesis was that grain quality and yield of maize (Zeamays L.) in north-west Pakistan are enhanced by increasing the rate of N, and that response to applied N is greater with an increase in the number of N split applications at high plant density compared to low density. RESULTS: Field experiments were carried out on maize (cv. Azam) in summer 2002 and 2003 consisting of two planting densities and three N rates as main plots, and six split N applications as sub-plots. Year 1 had higher shelling percentage and stover yield (SY). Harvest index (HI) decreased but SY increased with increase in plant density. Increase in N rate and number of split N applications increased grain weight and protein content, HI and SY. CONCLUSION: The highest N rate in four to five split applications increased maize grain quality and yield at both densities. Maize response to the interactive effect of year x plant density, year x N rate, and year x N timing suggests zonal specific effective N management practices for sustainable maize production in different agro-ecological zones. PMID- 20364484 TI - Health Practitioners Disciplinary Tribunal--professional misconduct (Med08/102P). PMID- 20364483 TI - Oral health checkup: progress in tough fiscal times? AB - Almost ten years after the surgeon general's report designating dental disease as the "silent epidemic," the nation continues to struggle with adequate access to and utilization of dental services. This is particularly true for low-income individuals, who experience more than twice the amount of untreated dental disease as their higher-income peers. This issue brief reviews sources of dental coverage for low-income children and adults and the challenges these programs face. It highlights some examples of state Medicaid initiatives to improve access and utilization for children and the progress of these initiatives. Finally, it examines the potential effects of the economy on dental coverage for low-income populations. PMID- 20364485 TI - Preliminary findings from H1N1 survey. PMID- 20364486 TI - Persuasion: an essential competency for the nurse leader. PMID- 20364487 TI - Polar bear alert! PMID- 20364488 TI - Metaphorically speaking: I am a? PMID- 20364489 TI - ANCC's Pathway to Excellence Program. PMID- 20364491 TI - Closing the door to conflict. PMID- 20364492 TI - Get certified-or lose your job: time running out for technicians. PMID- 20364493 TI - Should we keep hemoglobin levels as a viable outcome measure? AB - In conclusion, the most important priority is to shift thinking to ESA dose exposure and away from focusing on the target Hb level. More attention needs to be spent on developing strategies to minimize exposure to high doses of ESAs. Possible strategies might include the subcutaneous administration of ESAs, treating a patient with an elevated ferritin, identifying sources of blood losses, treating infections and/or an inflammatory focus, and the use of computerized protocols. An equally important goal should be to change the CMS QIP anemia measure to a target Hb >9 g/dL. This modification in the QIP anemia measure is supported by the evidence from both the Normal Hematocrit trials and TREAT. If one models the effect of this QIP on the dialysis patient population as a whole, the majority of achieved Hb concentrations will likely be <11 g/dL (similar to the reported findings in the Normal Hematocrit study--see Figure 1). Lastly, translational studies and clinical trials are necessary to test whether exposure to high doses of ESAs explains the higher risk observed in CHOIR, TREAT, and the Normal Hematocrit study. PMID- 20364494 TI - Imagine it: an America without health care reform. PMID- 20364495 TI - Applying the Life Safety Code: are you ready? AB - Summary Noteverysituationwillfitneatlyinto the "K-tags." As the rules are applied, more interpretations will follow. CMS is asking for input from providers, administrators, and fire associations to assist in developing a survey tool. Administrators andproviders should review the LSC requirements, determine whether their facility is under the jurisdiction of their state's regulations or the federal LSC, and take the necessary steps to be within compliance with the regulations. PMID- 20364496 TI - Changing the models and measurements of dialysis care. PMID- 20364497 TI - [Cold hurts the fingers. Warmth brings little improvement]. PMID- 20364498 TI - [Additional premiums of the national health insurance. How should I advise my patients?]. PMID- 20364499 TI - [Making use of the placebo effect in general practice! Pharmacy and pharmagie belong together]. PMID- 20364500 TI - [Updates from placebo research. The 3 component effect (interview by Dr. Carola Goring)]. PMID- 20364501 TI - [Rheumatoid arthritis patient with multiple pulmonary coin lesions. Metastases- what else?]. PMID- 20364502 TI - [Instead of long-term antiarrhythmia drug treatment--stand-by therapy for atrial fibrillation]. PMID- 20364503 TI - [70 % of patients prefer natural healing]. PMID- 20364504 TI - [Functional dyspepsia]. PMID- 20364505 TI - [Every eighth case of hypertension originates in the adrenal gland. For whom is it worthwhile to screen for an endocrine cause?]. PMID- 20364506 TI - [Primary hyperaldosteronism--more common than previously thought]. PMID- 20364507 TI - [Pheochromocytoma: current diagnostics and treatment]. PMID- 20364508 TI - [Arterial hypertension and subclinical Cushing's syndrome]. PMID- 20364509 TI - [Fungal infection of nails]. PMID- 20364510 TI - [Asthma therapy in the doctor's office]. PMID- 20364511 TI - [Naturopathic complex therapy: which patients benefit?]. PMID- 20364512 TI - Radical claim? PMID- 20364513 TI - Revis(it)ing nursing history. PMID- 20364514 TI - Feeling vulnerable? PMID- 20364515 TI - When caring becomes personal. PMID- 20364516 TI - Consider culture. PMID- 20364517 TI - Jars of clay. PMID- 20364518 TI - Can I give spiritual care when my spiritual life is in shambles? PMID- 20364519 TI - Mind, medications & mental disorders: a spiritual approach. AB - In mental illness, individuals may choose faith-based counseling as primary treatment, with medical care as a supportive adjunct. Biblical Framework Counseling (BFC) is based on belief of the Bible's sufficiency to address the root causes of mental disorders that are not otherwise physiologically caused. Clients address underlying spiritual issues while medical care and pharmacotherapy adherence are encouraged to support symptom relief. Consultation between patient, BFC counselor and healthcare clinician is emphasized to optimize outcomes. PMID- 20364520 TI - Mental illness: a modern-day leprosy? AB - Leprosy in the ancient world involved quarantine from family and society and great stigma. Similarly, mental illness today can involve separation, lost potential, and stigma. As with leprosy, most people misunderstand etiology, treatment, and prognosis in mental illness. Nurses are in a key position to educate, intervene, and improve mental health outcomes. PMID- 20364521 TI - Perspectives & perceptions: spiritual care and organizational climate in Christian schools. AB - Caring and spirituality are concepts Christian nursing programs transmit through explicit official, operational, and implicit hidden curricula. A measurable facet of the hidden curriculum is organizational climate. This study explored interrelationships between perspectives of spiritual care held by students and educators in Christian baccalaureate nursing programs, and their perception of organizational climate. Findings revealed that students who felt better cared for tended to have more positive perspectives of spiritual care. PMID- 20364522 TI - Promoting ethical development in nursing education and beyond. AB - Ethical nursing practice can be referred to as doing what is best for those who are the recipient of one's services, according to the recipient. However, clear cut lines of what is and is not in the best interest of the patient can become blurred. Nurses often encounter situations that require them to use ethical judgment. This article discusses how ethical decision making can be developed in students, new graduates, and nurses in practice. PMID- 20364523 TI - African American church health programs: what works? AB - The church is a community resource that can help address areas of health disparity for African Americans by offering programs focused on primary prevention. Use of a logic model as a program evaluation tool highlights church priorities and program linkages (problems, goals, objectives, activities, outputs, and outcomes), providing clear evidence about meeting program expectations. Faith community nurses can lead program development, easily incorporating logic models within programming efforts. Church-based programs that document positive outcomes enhance program usefulness and value as a community health resource. PMID- 20364524 TI - Practice against our beliefs. PMID- 20364525 TI - Obedience: going against the grain. PMID- 20364526 TI - Miracle on new year's. PMID- 20364527 TI - Sharing God's love in the workplace. PMID- 20364528 TI - Future challenges to health and public health services in Canada. PMID- 20364529 TI - Re-visioning public health ethics: a relational perspective. AB - Canada is in the forefront of thinking about the unique and complex issues of contemporary public health ethics. However, an inordinate focus on the urgent issues of emergency preparedness in pandemic and reliance on bioethical analysis steeped in the autonomy and individual rights tradition of health care and research do not serve adequately as the basis for an ethic of public health with its focus on populations, communities and the common good. This paper describes some concerns regarding the focus on pandemic ethics in isolation from public health ethics; identifies inadequacies in the dominant individualistic ethics framework; and summarizes nascent work on the concepts of relational autonomy, relational social justice and relational solidarity that can inform a re visioning of public health ethics. While there is still much work to be done to further refine these principles, they can help to reclaim and centre the common and collective good at risk in pandemic and other emergency situations. Minimally, these principles require a policy-making process that is truly transparent, fair and inclusive; is sensitive and responsive to the workings of systemic inequalities; and requires public recognition of the fact that we enter any crisis with varying degrees of inequity. Public policy response to crisis must not forseeably increase existing inequities. PMID- 20364530 TI - Meningococcal serogroup C conjugate vaccination in Canada: how far have we progressed? How far do we have to go? AB - Since routine meningococcal C conjugate vaccination was introduced into Canada in 2002, there have been a large regional variation in the routine programs, changes to the timing of the infant series in some provinces, and wide differences in catch-up programs. As immunization is viewed as a provincial responsibility, less attention has been paid to determining national coverage rates and the direct and indirect effects of the widely varying provincial/territorial vaccination programs on the nation as a whole. Canada's disjointed regional immunization campaigns leave the population at risk of disease for an extended length of time. The United Kingdom has proven that with a pro-active approach to planning, coordination, and implementation of a national immunization program, excellent long-term control of invasive meningococcal disease in a large population could be achieved in as little as one year. A summation of the current meningococcal immunization strategies used in Canada and an estimate of overall vaccine coverage of children and youth is provided. PMID- 20364531 TI - Consultation with health care professionals and influenza immunization among women in contact with young children. AB - OBJECTIVE: Primary health providers serve an important role in providing and promoting annual influenza immunization to high-risk groups and their close contacts. The purpose of this analysis was to determine whether consultation with a medical professional increases the likelihood of receiving a flu shot among women who have given birth in the past five years and to determine whether this association differs by type of medical professional. METHODS: Data were obtained from the Canadian Community Health Survey (2005), Cycle 3.1. Logistic regression was used to examine the association between receiving a flu shot in the past 12 months and consulting with family doctors, specialists, nurses, chiropractors, or homeopaths/naturopaths. RESULTS: Among the 6,925 women included in our sample, 1,847 (28.4%) reported receiving a flu shot in the past 12 months. After adjustment for socio-demographic characteristics and province of residence, women who received flu shots in the past 12 months were significantly more likely to consult with a family doctor (AOR 1.56, 95% CI 1.34-1.83) and significantly less likely to consult with a chiropractor (AOR 0.76, 95% CI 0.64-0.90) or a homeopath/naturopath (AOR 0.72, 95% CI 0.54-0.97) over the same time period. CONCLUSION: Consultation with family doctors was found to have the strongest association with annual flu shots among women in contact with young children, whereas consultation with alternative care providers was found to have an independent inverse association. Given the influenza-associated health risks for young children, medical professionals should promote immunization at the time of consultation for household contacts of young children, including pregnant women. PMID- 20364532 TI - [The impact of multiple vaccinations on vaccine schedule adherence and parental attitudes in Monteregie]. AB - OBJECTIVE: This study aimed to explore the impact of adding new vaccines on schedule adherence and parental opinion of multiple injections. METHOD: A descriptive cross-sectional study by self-administered questionnaire mailed to a stratified random sample of each of two cohorts of children drawn from the Monteregie Birth Register: the 2002-2003 cohort (old vaccination schedule) and the 2004-2005 cohort (new schedule). Two surveys were done: Survey 1 (fall 2005 winter 2006) questioned parents whose address could be validated by Canada411.ca; Survey 2 (fall 2006) surveyed parents whose address was validated by the Quebec health insurance board (RAMQ). Incomplete or missing vaccine data were completed by verifying the vaccinators' files. RESULTS: Analysis of schedule adherence by the Kaplan-Meier survival approach showed that the 2nd and 3rd doses of the DTaP P-Hib vaccine were received late by the youngest children compared to the oldest (median number of days late: 2 days for the 2nd vaccine (p = 0.013) and 4 days for the 3rd vaccine (p < 0.001)). Many parents (76%) prefer 2 to 3 injections during a single visit, and 61% fear an increase in the risk of side effects. CONCLUSION: Even if the evaluated lateness has only a small public health impact, parents must be reassured about the safety of multiple vaccines. PMID- 20364533 TI - A new approach to health research in Canada's North. AB - Over the past four years, despite low resource allocations to the North, northern residents and community organizations have taken significant initiatives towards the development of health research. In this commentary, we present a model for the development of northern health research based on our experiences in establishing the Institute for Circumpolar Health Research (ICHR) in the Northwest Territories. It is hoped that the lessons we have learned will inform decision-makers and encourage them to make strategic investments to support further health research capacity and institutional development within the North. Factors that have enabled the development of a health research institute in the North include leadership, a vision for health research, and the engagement of key partners and stakeholders. Challenges arise in the development of appropriate governance and policy for health research. There is an urgency to target resources to support the development of policies and governance for health research in northern jurisdictions. Both academic and community-based research need to be strengthened. PMID- 20364534 TI - Methylmercury blood guidance values for Canada. AB - Exposure to methylmercury (MeHg) from fish and marine mammal consumption continues to present a public health concern. To date, developmental neurotoxicity is the most sensitive health outcome, forming the basis for health risk assessments and the derivation of biomonitoring guidance values. This article summarizes existing Health Canada MeHg blood guidance values for general population and expands them to include a harmonized provisional interim blood guidance value of 8 microg/L based on the existing provisional Tolerable Daily Intake for children, pregnant women and women of childbearing age. Associated public health actions, according to age, sex, and level of exposure are recommended. PMID- 20364535 TI - A family affair: Aboriginal women's efforts to limit second-hand smoke exposure at home. AB - OBJECTIVE: The objective of this study was to explore factors influencing smoking in home environments and Aboriginal women's efforts to minimize exposure for their children and themselves. METHODS: A community-based ethnographic research study conducted in the northwest region of BC with the Gitxsan First Nations. The study included individual interviews and focus groups with 26 women ranging in age from 17 to 35, key informants (n = 15), elders (n = 9), middle-age women (n = 7), and youth (n = 6) from six reserve communities. RESULTS: Women experienced unique challenges in establishing smoke-free homes. Themes identified that describe these challenges include social dimensions of smoking in extended families, and the structural and relational influences on women's efforts to minimize household second-hand smoke to protect children's health. Narratives also included stories of success in women's efforts to reduce exposure to second hand smoke. CONCLUSION: Second-hand smoke presents a multifaceted challenge to Aboriginal women who are motivated to protect their health and the health of their children. Their efforts to implement smoke-free strategies in their homes should be supported. PMID- 20364536 TI - Can exclusive breastfeeding reduce the likelihood of childhood obesity in some regions of Canada? AB - OBJECTIVES: The prevalence of childhood obesity in Canada is a major concern. Studies report a small but significant inverse relationship between exclusive breastfeeding and childhood obesity. The study objectives were to determine the prevalence of overweight and obesity in a preschool population living in Newfoundland and Labrador (NL) and to examine the relationship between exclusive breastfeeding and preschool obesity. METHODS: This was a cross-sectional analysis of 1,026 children born in 2001 who participated in the Pre Kindergarten Health Fairs in 2005. Heights and weights were collected and body mass index (BMI) calculated. The BMI-for-age references used by the Centers for Disease Control (CDC) in the United States were used to classify the weight status of children. Infant feeding information was collected through a survey. The relationship between breastfeeding and childhood obesity was examined using logistic regression models controlling for child's age and gender, mother's education and smoking status, and whether the baby was preterm or full-term. RESULTS: In 2005, 65%, 19% and 16% of preschool children were normal, overweight and obese, respectively. 74% of women initiated breastfeeding and 43% exclusively breastfed to 3 months. Exclusive breastfeeding to 3 months was protective of preschool obesity (adjusted odds ratio (AOR) 0.65, 95% CI 0.45-0.96). CONCLUSION: Obesity is prevalent in preschool children in NL. Exclusive breastfeeding appeared to be a protective factor for obesity in preschoolers. Given the known benefits of breastfeeding and the adverse health consequences of obesity, efforts should be made to increase exclusive breastfeeding which may help to prevent the development of obesity in young children. PMID- 20364537 TI - A province-wide school nutrition policy and food consumption in elementary school children in Prince Edward Island. AB - OBJECTIVE: Although the majority of Canadian provinces have indicated that they have adopted new school nutrition policies, there have been few if any systematic evaluations of these policies. In Prince Edward Island, a nutrition policy for elementary schools was adopted province-wide in 2006. In the present study, we assessed the nutritional benefits of the new policy by examining changes in student food consumption prior to and one year following implementation of the policy. METHODS: We surveyed fifth and sixth grade children from 11 elementary schools in Prince Edward Island in 2001/02 (pre-policy implementation) and fifth and sixth grade children from the same 11 schools in 2007 (post-policy implementation). Food consumption was assessed using a self-administered validated food frequency questionnaire. We applied multilevel logistic regression to compare pre-/post-policy implementation differences in the proportion of students meeting Canada's Food Guide recommendations for vegetables and fruit (VF) and milk and alternatives (MA) and in the proportion of students consuming < 3 servings of low nutrient dense foods (LNDF) daily. RESULTS: Relative to students in 2001/02, students surveyed in 2007 were 2.14 (95% CI 1.62-2.82) times more likely to report consuming less than three daily servings of LNDF and were more likely to meet recommendations for VF (OR 1.44, 95% CI 1.00-2.07) and MA (OR 1.27, 95% CI 0.98-1.64). CONCLUSION: The present study is the first in Canada to show favourable changes in student food consumption that parallel the introduction of a school nutrition policy. PMID- 20364538 TI - Regional and temporal trends in migration among people living with HIV/AIDS in British Columbia, 1993-2005. AB - OBJECTIVES: To examine regional and temporal trends in migration among patients receiving HIV treatment in British Columbia (BC). METHODS: Patients initiating antiretroviral therapy in BC between January 1993 and November 2004 were followed until November 2005. Migration was calculated as the cumulative number of times a patient's residential address changed during their course of treatment. Analyses were performed at the provincial and at the regional health authority (HA) and local health area levels. Demographic methods were used to estimate the in- and out-migration rates, indices of dissimilarity and concentration across regions over time. RESULTS: A total of 3,588 participants were followed during the study period. Individuals who migrated most often migrated to the Vancouver Coastal HA (from the Interior: 30%, Fraser: 41%, Vancouver Island: 28%, and Northern: 19%), specifically the city of Vancouver, which has been treating the most patients with HIV since the early stages of the epidemic. We also showed that this movement intensified as more contemporary HAART regimens became available (p value for trend < 0.01). DISCUSSION: Our results demonstrate that migration among people with HIV in BC is not homogeneous, with areas around large urban centres having the highest influx of patients. It is thus important that health authorities in BC work in partnership to monitor and evaluate accessibility of HIV-related health care services to ensure universal access for all patients. Furthermore, enhanced HIV care and support services need to be developed, on a province-wide basis, and funding allocation needs to be adjusted to reflect patient migration in BC. PMID- 20364539 TI - Seroprevalence and correlates of HIV and HCV among injecting drug users in Edmonton, Alberta. AB - BACKGROUND: Injection drug users (IDUs) are at risk for acquiring human immunodefiency virus (HIV) and hepatitis C virus (HCV) via parenteral and sexual transmission. We determined the seroprevalence and correlates of HIV and HCV for IDUs recruited in Edmonton, Alberta. METHODS: Edmonton was one site of a multi site, national survey (I-Track Study). From April to June 2005, IDUs were recruited and administered a questionnaire collecting information on demographics, drug use, sexual behaviours, and HIV/HCV testing behaviours. Finger prick blood samples were collected for serology testing. Seroprevalence of HIV and HCV was determined and correlates of infection were assessed using logistic regression. RESULTS: Of 275 IDUs, 68% were male, the median age was 38 years and 70.6% were Aboriginal. HIV prevalence was 23.9%, HCV prevalence was 66.1% and HIV/HCV co-infection was 22.8%. Cocaine (36.9%) was reported to be the drug injected most often in the previous six months. Correlates for HIV were sex trade (OR 2.9, 95% CI 1.0-8.3) for women, and older age (OR 1.1, 95% CI 1.0-1.2) and needle exchange program (NEP) use (OR 5.7, 95% CI 1.3-23.7) for men. For women, having a casual sex partner was protective for HCV (OR 0.28, 95% CI 0.10-0.78). Independent correlates for HCV among males included age (AOR 1.2, 95% CI 1.1-1.3) and younger age of first injection (AOR 0.92, 95% CI 0.87-0.96). CONCLUSION: The high HIV and HCV prevalence found in this study among IDUs in Edmonton highlights the complex needs of the IDU community and the continued need for targeted programming. PMID- 20364540 TI - The epidemiology of weight perception: perceived versus self-reported actual weight status among Albertan adults. AB - BACKGROUND: To understand, prevent, and manage weight-related health issues, researchers and clinicians rely on the ability to identify those at risk. Prevention and management strategies may also rely on accurate self-perception of weight and body composition in the general population. METHODS: We analyzed data from The Tomorrow Project (n = 7,436), a prospective cohort study enrolling adults aged 35-69 years, in Alberta, Canada. Weight perception accuracy was defined based on body mass index (BMI), waist circumference (WC), and a combined (BMI and WC) risk profile. RESULTS: The majority of participants correctly perceived themselves as overweight. Women were more accurate than men in identifying themselves as overweight. In terms of inaccuracy, more normal-weight women than men perceived themselves to be overweight, while more overweight men than women perceived themselves as about the right weight. When using the combined risk profile, all men with normal weight (BMI) but higher risk WC perceived their weight as about right whereas just under half of men who were overweight (BMI) but lower risk WC perceived their weight as about right. For women, a much higher proportion recognized their weight status as overweight when only BMI was elevated compared to when only WC indicated higher risk. DISCUSSION: Adults in our sample showed reasonable accuracy in weight perception. Gender differences reveal that women were more accurate than men in identifying themselves as overweight. Incongruence between weight status indicators was noted, indicating the importance of using both BMI and waist circumference as health status measures. PMID- 20364541 TI - Validity of administrative data claim-based methods for identifying individuals with diabetes at a population level. AB - OBJECTIVES: This study assessed the validity of a widely-accepted administrative data surveillance methodology for identifying individuals with diabetes relative to three laboratory data reference standard definitions for diabetes. METHODS: We used a combination of linked regional data (hospital discharge abstracts and physician data) and laboratory data to test the validity of administrative data surveillance definitions for diabetes relative to a laboratory data reference standard. The administrative discharge data methodology includes two definitions for diabetes: a strict administrative data definition of one hospitalization code or two physician claims indicating diabetes; and a more liberal definition of one hospitalization code or a single physician claim. The laboratory data, meanwhile, produced three reference standard definitions based on glucose levels +/- HbA1c levels. RESULTS: Sensitivities ranged from 68.4% to 86.9% for the administrative data definitions tested relative to the three laboratory data reference standards. Sensitivities were higher for the more liberal administrative data definition. Positive predictive values (PPV), meanwhile, ranged from 53.0% to 88.3%, with the liberal administrative data definition producing lower PPVs. CONCLUSIONS: These findings demonstrate the trade-offs of sensitivity and PPV for selecting diabetes surveillance definitions. Centralized laboratory data may be of value to future surveillance initiatives that use combined data sources to optimize case detection. PMID- 20364542 TI - [The practice and acceptance of physician preventive medicine services in a Montreal university hospital and the obstacles that deter their implementation.]. AB - OBJECTIVES: Present a picture of physicians' preventive clinical practices (PCP) at a university medical centre, and identify the obstacles that hinder their implementation. METHOD: Self-administered questionnaire survey addressed to 367 general practitioners and specialists working at the Centre hospitalier de l'Universite de Montreal (CHUM) in 2006. RESULTS: Respondents claim to be recommending PCP (often or very often) in approximately 60-82% of cases. Women physicians report a larger integration for screening and vaccination (p < 0.05). General physicians claim to apply or recommend PCP more frequently than specialists (p < 0.05), except for anti-tobacco counseling. Lack of time (82%) and deficiencies in continuity of treatment (75%) are considered by the majority of respondents as major obstacles to the realization of PCP. Most participants (99%) consider delivering preventive services to be part of their role and 98% claim to be motivated to integrate PCP into their practice. However, almost half of physicians do not apply preventive recommendations to their own life and at least two thirds of them doubt the efficacy of counseling. CONCLUSION: Despite observed encouraging results, actions must be taken to improve the integration of PCP to general and specialized health care and to bring physicians around to adopting healthy lifestyle habits themselves. PMID- 20364543 TI - Socio-economic status and smoking in Canada, 1999-2006: has there been any progress on disparities in tobacco use? AB - OBJECTIVES: Comprehensive tobacco control policies implemented in Canada have succeeded in lowering overall smoking prevalence; however, the extent to which they have impacted socio-economic disparities in tobacco use is not known. This study examined smoking rates and related measures across socio-economic groups over a 7-year period in Canada. METHODS: Regression analyses tested associations between smoking-related outcomes (prevalence, frequency, consumption, quit intentions and attempts, quit ratios), education level and time, using data from adults 25 years and older who completed the 1999 to 2006 waves of the Canadian Tobacco Use Monitoring Survey (CTUMS), a repeated cross-sectional survey with nationally representative samples (n = 86,971). RESULTS: Between 1999 and 2006, smoking prevalence, daily smoking, and cigarette consumption decreased, while the proportion of smokers who planned to quit increased, as did the proportion of ever-smokers who had quit. However, significant educational differences were observed: Canadians with less education had greater odds of current smoking (prevalence approximately doubled between the most and least educated groups) and daily smoking, and consumed more cigarettes, compared to university graduates. Highly-educated ever-smokers were also more likely to have quit smoking. These disparities remained stable over the time period studied. Intentions and attempts to quit were not consistently associated with education. CONCLUSIONS: The decline in smoking among Canadians between 1999 and 2006 represents a major public health achievement. However, considerable smoking-related disparities exist between socio-economic groups, and have changed very little. Therefore, while recent programs and policies have succeeded in reducing overall tobacco use, they have not addressed socio-economic disparities. PMID- 20364544 TI - Physician retention in rural Alberta: key community factors. AB - OBJECTIVES: As part of a larger case study exploring physician retention factors and strategies employed by rural communities, the objective of this analysis was to explore the community factors that promoted physician retention. METHODS: A qualitative, collective case study design was employed to study four rural communities (cases) in Alberta that retained family physicians for four years or longer. Participants included physicians, staff members, spouses and community members (all were patients from the communities studied). Communities were selected through a retention-specific matrix; each quadrant represented a particular community typology. Case data collected from interviews, documents and observations were analyzed, and similarities and differences among cases were assessed. RESULTS: A range of community factors that could influence physicians' decisions to stay in a particular community were described by participants. Four themes, Appreciation, Connection, Active Support and Physical/Recreational Assets, were positively related to physician retention in the four communities studied. These community factors existed to different degrees but were present in all communities. Reciprocity was a fifth factor that emerged in three of the four communities studied. CONCLUSION: Physicians, policy-makers, community members and health care professionals are encouraged to consider the community domain when planning and implementing strategies to retain rural physicians and other health care professionals. The four communities studied were able to promote retention of their primary care physicians by showing appreciation to them, building connections with them and their families, actively supporting their physicians and local health facilities, maintaining and improving local physical/recreational amenities, and nurturing reciprocal rapport with physicians. PMID- 20364545 TI - Thinking about aboriginal KT: learning from the Network Environments for Aboriginal Health Research British Columbia (NEARBC). AB - OBJECTIVE: Creating effective and actionable research has become increasingly important for the health disciplines. Despite greater attention to knowledge translation (KT) in the health research, policy, and professional literature and the mounting need for strategic action to reduce the burden of ill health experienced by Aboriginal people in Canada, little time has been dedicated to understanding KT in Aboriginal health research contexts (Aboriginal KT). The purpose of this study was to explore and discuss the unique qualities of Aboriginal KT. METHODS: An exploratory case study of the Network Environments for Aboriginal Research British Columbia (NEARBC) was undertaken, in which qualitative interviewing with experts associated with the network was conducted. RESULTS: Four themes were revealed from the analysis of 10 semi-structured qualitative interviews: 1) Definitional debate, 2) "Aboriginal" KT, 3) Doing KT, and 4) KT roles. These themes highlight the definitional complexity, practical confusion, multidisciplinary nature, and lack of accountability related to Aboriginal KT. DISCUSSION: The information gained from the study participants adds some important insights to the current literature. It also identifies areas where future discussion may help improve the understanding and meaning of KT in Aboriginal health research contexts, as well as its application in practice. The health disparities of Aboriginal people in Canada are a call for action with regards to KT and this study provides some basic information and advice on ways to move the research and policy agenda forward. PMID- 20364546 TI - Are Canadian women achieving a fit pregnancy? A pilot study. AB - OBJECTIVES: Canadian recommendations exist for energy intake (EI), physical activity (PA) and gestational weight gain (GWG) to help pregnant women avoid excessive GWG and attain "fit pregnancies". Our objectives were: 1) to measure daily EI, PA and GWG to observe whether pregnant women were meeting recommendations, 2) to explore the impact of health care provider advice on PA and GWG, and 3) to determine behaviours associated with recommended weekly GWG. METHODS: Women (n = 81) were recruited from prenatal classes. Current weight and self-reported pre-pregnancy weight were documented. Current PA levels and provider advice for PA and GWG were surveyed using questionnaires. Dietary recalls and pedometer steps were recorded for three and seven days respectively. RESULTS: The majority of our women were classified as having average pre pregnancy body mass indices (BMI) of 23.3 +/- 4 kg/m2, average EI of 2237 kcal/d and energy expenditure (EE) of 2328 kcal/d, but with weekly rates of GWG in excess of current recommendations despite having received advice about GWG (74%) and PA (73%). Most were classified as sedentary (< 5000 steps/day (d)) and 36% as low active (< 7500 steps/d). Women were most likely to achieve appropriate GWG if their total PA was > 8.5 MET-hr/wk. CONCLUSION: Health care providers need to provide appropriate PA and GWG guidelines to pregnant women. Development of pregnancy step and MET-hr/wk recommendations are warranted in order to promote greater PA during pregnancy. PMID- 20364547 TI - Lived experience of economic and political trends related to globalization. AB - OBJECTIVE: A multi-method case study examined how the economic and political processes of globalization have influenced the determinants of health among low income children in Saskatoon, Saskatchewan, Canada. This paper presents the results from the qualitative interview component of the case study. The purpose of the interviews was to uncover the lived experience of low-income families and their children in Saskatoon with regards to political and economic trends related to globalization, an important addition to the usual globalization and health research that relies primarily on cross-country regressions in which the personal impacts remain hidden. METHODS: In-depth phenomenological interviews with 26 low income parents of young children (aged zero to five) who were residents of Saskatoon. A combination of volunteer and criterion sampling was used. Interview questions were open-ended and based upon an analytical framework. Analysis proceeded through immersion in the data, a process of open coding, and finally through a process of selective coding. RESULTS: The larger case study and interviews indicate that globalization has largely not been benefiting low-income parents with young children. Low-income families with young children were struggling to survive, despite the tremendous economic growth occurring in Saskatchewan and Saskatoon at the time of the interviews. This often led to participants expressing a sense of helplessness, despair, isolation, and/or anger. CONCLUSIONS: Respondents' experiences suggest that globalization-related changes in social conditions and public policies and programs have great potential to negatively affect family health through either psychosocial effects in individuals and/or decreased levels of social cohesion in the community. PMID- 20364548 TI - Protective vascular treatment of patients with peripheral arterial disease: guideline adherence according to year, age and gender. AB - OBJECTIVES: To evaluate vasoprotective pharmacological treatment of patients with peripheral arterial disease (PAD) according to: 1) year, 2) age and 3) gender. METHODS: An observational retrospective study was conducted to evaluate the systemic vascular treatment of a population-based cohort of patients with PAD > or = 50 years old, discharged from a tertiary-care teaching hospital between January 1, 1997 and December 11, 2006. Data were obtained from the Regie de l'assurance maladie du Quebec. Drugs evaluated included antiplatelet agents (APs), statins (STs) and angiotensin converting enzyme inhibitors (ACEIs), and a combination of all three. Proportions of patients treated were compared according to year, age and gender using Chi-square. RESULTS: The mean age of the study population (5962 individuals) was 73.2 +/- 9.1 years; 43.8% were women. After hospital discharge, 71.6%, 47.6%, 42.2% and 20.6% were taking respectively, an AP, statin, ACEI or all three. Protective treatment improved significantly from 1997 to 2006. Significantly more subjects 50-64 years used a statin or all three agents, compared to subjects > or = 65 years (statins: 56.6% vs. 45.8%, all three: 26.2% vs. 19.5%; p < 0.001). Significantly more men than women used statins (49.1% vs. 45.6%; p < 0.001) and ACEIs (44.5% vs. 39.3%; p < 0.001). Similarily, use of all three agents was 22.4% for men and 18.2% for women (p < 0.001). CONCLUSIONS: Although systemic vascular treatment received by patients with PAD has increased in the past years, it remains suboptimal, particularly for older patients and women. Strategies to improve adherence to treatment guidelines should be developed for these high-risk populations. PMID- 20364549 TI - Detection of later stage breast cancer in First Nations women in Ontario, Canada. AB - OBJECTIVE: To compare the distribution of stage at breast cancer diagnosis between First Nations (FN) and non-FN women, and to investigate factors associated with later diagnosis in FN women. METHODS: A case-case design was employed to compare FN women (N = 287) to a frequency-matched random sample of women (N = 671) from the general population diagnosed with breast cancer in the Ontario Cancer Registry. Women were matched (2:1) on period of diagnosis (1995 1999, 2000-2004), age at diagnosis (< 50 vs. > or = 50), and Regional Cancer Centre (RCC). Stage and data relevant to the determinants of stage were collected from medical charts at the RCCs. The association between stage (stage II + vs. I) and FN status was modeled using logistic regression analyses; for FN women, the association between risk factors and stage was examined. RESULTS: FN women (66%) were diagnosed with a later stage significantly more often than non-FN women (56%). FN women with a non-screened cancer (OR 5.03, 95% CI 2.48-10.21) and those who were overweight or obese (OR 2.98, 95% CI 1.27-6.98 and OR 4.46, 95% CI 1.95 10.21, respectively) were significantly more likely to be diagnosed at a later stage. Having a comorbidity reduced the odds of a later stage (OR 0.51, 95% CI 0.27-0.96) in FN women. CONCLUSION: This study demonstrates the need for FN women, in particular those who are not accessing the health care system, to participate in breast screening programs aimed at detecting breast cancers earlier with a better prognosis. These findings suggest that the cancer care system in Ontario should better target this population through increasing awareness and access to screening. PMID- 20364550 TI - Community and public health nursing practice: two new studies sound the alarm. PMID- 20364551 TI - Prevalences and association of ECG findings and cardiovascular risk factor in Shinawatra employees. AB - OBJECTIVES: There is significant incline trend in cardiovascular disease (CVD) mortality in developing countries such as Thailand and it is also the major contributor to the burden of premature mortality and morbidity throughout the world. In order to have well-stratified primary prevention plan, this study reports the prevalence of Electrocardiogram (ECG) abnormalities, as categorized by ECG Minnesota coding, and the association with major cardiovascular risk factors in Thailand. MATERIAL AND METHOD: In this study, we use the same data from a previous survey at Shinawatra Employee but only subjects with available ECG's were recruited in our study. Standard supine 12-lead ECG data were collected; all amplitude and intervals were measured and entered into a computer manually. Then the ECG was coded according to Minnesota Coding system. The study characteristics, the prevalence of major cardiovascular risk factors and ECG abnormalities were calculated. RESULTS: A total of 1,485 subjects were recruited in this study, 638 (43.0%) were male and 847 (57.0%) were female. The overall mean aged was 34.4 (5.4). The level of major cardiovascular risk factors among men and women respectively were: total Cholesterol 215.6 (41.0) mg/dl (5.6 (1.1) mmol/l), 202.8 (35.3) mg/dl (5.3 (0.9) mmol/l); LDL-cholesterol 139.1 (37.0) (3.6 (1.0) mmol/l), 123.6 (31.9) (3.2 (0.8) mmol/l). Hypercholesterolemia was 65.3%, 49.8%. The mean systolic and diastolic blood pressures were 121.5 (13.9) mmHg and 81.4 (10.5) mmHg, 111.7 (12.2) mmHg and 74.5 (8.6) mmHg; hypertension 21.0%, 4.2%; fasting blood sugar 95.5 (15.8) mg/dl (5.3 (0.9) mmol/l), 88.0 (8.6) mg/dl (5.1 (0.5) mmol/l); diabetes mellitus 3.3%, 0.5%; body mass index 23.5 (3.5) (kg/m2), 21.3 (3.1) (kg/m2); obesity 30.7%, 11.0%; smoking 12.3%, 14.0%. The prevalence of ECG abnormalities, as categorized based on the Minnesota coding criteria, among men and women respectively were: Q/QS wave abnormalities (Code 1) 2.2%, 0.8%; S-T-J segment depression (Code 4) 0.5%, 1.4%; T-wave inversion (Code 5) 1.4%, 9.6%; atrioventricular conduction abnormalities (Code 6) 2.5%, 0.8%; and ventricular conduction abnormalities (Code 7) 0.2%, 0.2%. CONCLUSIONS: This study reports higher prevalence of having major cardiovascular risk factors as compared to previous epidemiological studies in Thailand which should heighten the Ministry of Public Health concern to launch a better stratified preventive plan to combat the rising of coronary artery disease in the future. Moreover, this study is also the first study to report the prevalence of ECG abnormalities, as determined on the basis of the Minnesota coding criteria, and the association between major cardiovascular risk factors and the prevalences of several electrocardiographic findings in adult men and women in Thailand. PMID- 20364552 TI - Evaluation of the firebird sirololimus eluting stent in all comers with coronary artery stenosis. AB - OBJECTIVE: Percutaneous coronary intervention (PCI) has been widely used to treat obstructive coronary artery disease. With the advent of drug-eluting stent (DES) in real world registry was proved as promising therapy. The limitation of the use of DES is the limited health care expenditure. We propose the use of Chinese made DES among Thai patients and that this will solve the cost issue. The clinical result of this DES has not been well known. METHODS: Prospective study from November 2005 to March 2007 using the structured registry form to evaluate the safety and efficacy of new Chinese made Firebird sirolimus eluting stent (Firebird SES) on clinical parameters from in-hospital, 30 days and 12 months or longer term follow-up. End point is major adverse cardiac event (MACE) including death, MI, TLR and CABG at 30 day and cumulative MACE at 12 month follow-up. RESULTS: Ninety consecutive patients who were treated with Firebird stent implantation (107 target lesions) were analyzed. Angiographic success (defined as < 30% diameter stenosis) was 85%. Procedure success was 77.8%. MACE at 30 day was 16.6%, cumulative MACE at 12 months was 18.8%. There were total 9 deaths during the study period, two deaths occurred at before 30 days, 3 deaths occurred before 12 months and other 4 deaths occurred after 12 months to 1305 days. Eighty patients (88.9%) had either office visit or telephone call follow-up after 12 months, 38 patients (42.2%) underwent clinical driven coronary arteriography, binary restenosis was 26.3%. Shock and smoking history was the analyzed predictor of MACE at follow-up. CONCLUSION: The implantation of Firebird DES in unselected patients (all comers) is safe, effective and could be an alternative choice of stent for Thai patients. PMID- 20364553 TI - Early and intermediate outcomes of left main coronary intervention. AB - OBJECTIVE: We examined the immediate and long-term outcomes after stenting of all comers for left main coronary artery (LMCA) stenoses. BACKGROUND: Left main coronary artery disease is regarded as an absolute contraindication for coronary angioplasty. Recently, several reports on protected or unprotected LMCA stenting, or both, suggested the possibility of percutaneous intervention for this prohibited area. MATERIAL AND METHOD: Eighty-one consecutive patients with LMCA stenoses were treated with stents. The post-stent antithrombotic regimens were aspirin and clopidogrel. The major adverse cardiac events (MACE) including death, Q-wave myocardial infarction, or repeat target lesion revascularization were followed. Patients were followed very closely and all attended office visit at 12 months. RESULTS: The procedural success rate was 86.4%, with no episodes of acute thrombosis. Follow-up angiography was performed in 30 of 65 eligible patients (46.2%). Angiographic restenosis occurred in eight patients (9.9%). Cumulative death occurred in 16 patients (19.7%). MACE at 30 day and 12-month was 12.3% and 33.3% respectively. From multivariate analysis, dialysis (HR =3.22, p = 0.048), urgent PCI (HR =2.39, p = 0.036), post-procedure TIMI flow < 3 (HR =25.99, p = 0.001) and final kissing balloon inflation (HR = 0.30, p = 0.04) were independent predictors of MACE at 12-month. There was one definite late stent thrombosis (1.2%). CONCLUSION: Stenting of LMCA stenosis may be a safe and effective alternative to CABG in carefully selected patients. Further studies in larger patient populations are needed to assess late outcome. PMID- 20364554 TI - Prediction of contrast-induced nephropathy in diabetic patients undergoing elective cardiac catheterization or PCI: role of volume-to-creatinine clearance ratio and iodine dose-to-creatinine clearance ratio. AB - OBJECTIVE: To assess a role of volume-to-creatinine clearance ratio (V/CrCl) and iodine dose-to-creatinine clearance ratio (I-dose/CrCl) in predicting contrast- induced nephropathy (CIN) in diabetic patients undergoing elective cardiac catheterization or percutaneous coronary intervention (PCI). BACKGROUND: In diabetic patients undergoing cardiac catheterization or PCI, the incidence of CIN is higher than in non-diabetic patients. High doses of contrast media also increase the likelihood of renal dysfunction. The ratio of the volume of contrast media to creatinine clearance (V/CrCl) and iodine dose-to-creatinine clearance (I dose/CrCl) has been shown to correlate with the area under the curve of contrast media concentration over time and was used to predict the occurrence of CIN in unselected patients. No study has been conducted specifically in diabetic patients undergoing cardiac catheterization or PCI before. MATERIAL AND METHOD: We conducted a prospective, single center study. The V/CrCl and I-dose/CrCl were calculated in diabetic patients undergoing elective cardiac catheterization or PCI. An increase in serum creatinine of > 0.5 mg/dl or > 25% by 7 days from baseline was considered CIN. The incidence of CIN was determined. The predictive value of V/CrCl and I-dose/CrCl for CIN were assessed using multivariable logistic regression. RESULTS: The total number of patients that had been enrolled in the study was 248; Male 50.8%. The overall incidence of CIN was 5.2%. The mean age for the entire population was 65 +/- 9 years; the mean body mass index was 25.6 +/- 4.0 kg/m2; and the mean creatinine clearance was 60.6 +/- 27.4 ml/min. The mean values of V/CrCl for patients with and without CIN were 3.7 +/- 2.9 and 2.2 +/- 1.7 (p = 0.041). The mean values of I-dose/CrCl for patients with and without CIN were 1.31 +/- 0.94 and 0.82 +/- 0.63 (p = 0.042). The receiver operator characteristic curve analysis indicated that a V/CrCl ratio of 2.60 and I-dose/CrCl of 0.98 were fair predictors of CIN. After adjusting for other known predictors of CIN, a V/CrCl ratio > or = 2.60 remained the only significant predictor of CIN (Odds ratio 5.8; 95% confidence interval 1.7-19.4, p = 0.005). CONCLUSIONS: A V/CrCl ratio > or = 2.60 was a significant predictor of CIN in diabetic patients undergoing elective cardiac catheterization or PCI. PMID- 20364556 TI - Clinical presentation and echocardiographic findings of Thai patients with Marfan syndrome. AB - OBJECTIVE: Marfan syndrome is an inherited disorder with systemic connective tissue involvement. The condition is clinically diverse and extremely pleiotropic. Though several articles had been published, no data from Thai individuals has ever been reported. Here we presented clinical manifestations and echocardiographic findings of Thai patients with Marfan syndrome. MATERIAL AND METHOD: Clinical and echocardiographic data were collected from series of Thai index cases with diagnosis of Marfan syndrome at Siriraj Hospital between 1995 and 2009. Demographic data, clinical presentations, and echocardiographic data were reviewed and analyzed. RESULTS: Fifty individuals and thirty echocardiograms were identified. Thirty eight individuals (76%) fulfilled clinical criteria for definite Marfan syndrome and twelve individuals (24%) were incomplete Marfan syndrome. The majority of those individuals had significant organ involvement including dilatation of ascending aorta (78%), ectopia lentis (54%), and skeletal involvement (96%). CONCLUSIONS: In summary, this is the first report of clinical manifestation and echocardiographic findings of Thai patients with Marfan syndrome. PMID- 20364555 TI - The effectiveness of "Siriraj Leg Lock" brace on back pain after percutaneous coronary intervention: PCI. AB - BACKGROUND: The most common problem experienced by patients after Percutaneous Coronary Intervention (PCI) is back pain. After the procedure, patients are restricted to complete bed rest with no hip flexion for up to 10 hours, causing much discomfort, especially back pain. In some patients, anxiety arises due to limited movement, with the belief that movement might cause re-bleeding from the wound. To alleviate these problems, the "Siriraj Leg Lock" brace or SLL was initiated to confine the hip while allowing patients to freely move other parts of their body without complicating the wound. Hence, anxiety is relieved and mobility can lower the chance of getting back pain with more comfort. OBJECTIVE: The aims of this experimental study were to investigate the effect and satisfaction of SLL on back pain in post-PCI patients, and to compare bleeding and/or hematoma occurrences at the site of incision between experimental and control groups. MATERIAL AND METHOD: The randomized controlled trial (RCT) was conducted in 100 patients who underwent coronary angioplasty and/or stent placement interventions and received post procedural care at the intermediate cardiac care ward, Her Majesty Cardiac Center from December 2006 to February 2007. The control group (49 patients) was to get standard care after the intervention, whereas the experimental group (51 patients) was fitted with the SLL device to allow free mobility right after the procedure. RESULTS: Lower maximum back pain scores and mean back pain scores in the experimental group than in the control group, with statistical significance (p < 0.001). Back pain score reduced from the day of admission in the experimental group after applying SLL, but increased in the control group. The occurrence of hematoma in both groups was not significantly different (p = 0.114). The experimental group with the SLL could freely change positions from upright to decubitus without any effects to the wound, feeling more comfortable and experiencing less back pain. Patients' satisfaction towards the SLL from 1 to 5 scale was 4.3. The satisfaction was evident especially in patients who had previous PCI experience, and desired to ask for SLL application if a future procedure to be needed. CONCLUSION: Using SLL after sheath removal post PCI allows the patient to freely change position without any effects to the wound and reduces back pain with more patients' satisfaction. PMID- 20364557 TI - Comparison of the incidence of imidapril and enalapril induced cough. AB - BACKGROUND: Imidapril is an angiotensin converting enzyme (ACE) inhibitor without a sulfhydril group which has been shown from previous study to have low incidence of ACE inhibitor induced cough. OBJECTIVE: To compare the incidence of cough between two ACE inhibitors, imidapril and enalapril. MATERIAL AND METHOD: A comparative cross over study was performed in 119 patients with hypertension or left ventricular dysfunction. Patients were assigned to one of the two treatment groups, either a group receiving imidapril or enalapril for 4 weeks (Period I) and then these same groups were crossed over to receive either enalapril or imidapril for 4 weeks (Period II). The occurrence of cough during treatment was monitored by interviewing the patients. RESULTS: The incidence of cough was 44 % while on imidapril treatment and 66% while on enalapril treatment (p = 0.0014). The antihypertensive effects of two drugs were not different. CONCLUSION: The incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects between the two ACE inhibitors. PMID- 20364558 TI - Hypertensive emergencies remain a clinical problem and are associated with high mortality. AB - OBJECTIVE: We suspect that hypertensive emergencies remain a clinical problem and data on their long-term prognosis are lacking. This study was conducted in order to determine the frequency, management, and outcome of hypertensive emergencies in this era, in which hypertension treatment is more effective than in the past. MATERIAL AND METHOD: We reviewed the medical records of patients with hypertensive emergencies admitted to the medical wards of Siriraj Hospital in 2003 and collected data on their characteristic, management, investigations, and follow-ups through 31 December 2007. RESULTS: There were 184 patients included. Hypertension has been previously diagnosed in 89% of cases. Nearly half also had diabetes mellitus and around a quarter had chronic kidney failure. Mean +/- SD of blood pressure at presentation was 205.96 +/- 21.36/114.60 +/- 20.59 mmHg. Cardiac complications and stroke accounted for 71% and 23% of all target organ damage, respectively. Intravenous nitroglycerine and furosemide were most frequently prescribed. Additional investigations to search for the causes of hypertension were performed in only 55 cases. The average hospital stay was 9.8 days. The in-hospital mortality rate was 15%. Some 26% of patients were lost to follow-up and another 20% died later. Only 19% of patients had regular follow-ups until the end of 2007 and remained on an average of 2.4 antihypertensive drugs. CONCLUSION: Hypertensive emergencies are usually found in patients with a history of hypertension and diabetes mellitus or kidney failure. Recommended investigations usually failed to identify the cause of hypertension. The mortality rate of these patients was extremely high while their adherence to treatment was extremely poor. PMID- 20364559 TI - Differential expression of Th2 chemokine receptors on T cells from atopic and nonatopic asthmatics in response to Der p 1-pulsed dendritic cells. AB - BACKGROUND: In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3 and CCR4 and migrate to their ligands: eotaxin, monocyte derived chemokine (MDC) or CCL22, thymus- and activation-regulated chemokine (TARC) or CCL17. However little is known about the regulation of these chemokine receptor axes by Der p 1-pulsed dendritic cells in house dust mite (HDM) sensitive and non-atopic asthmatics. OBJECTIVE: The aim was to investigate the modulatory effects of Der p 1-pulsed DCs on the expression of CCR3 and CCR4 on CD4+ T cells of HDM-sensitive and non-atopic asthmatics. MATERIAL AND METHOD: Using real-time RT-PCR and flow cytometry analysis, the expression of CCR3 and CCR4 were assessed in autologous CD4+ T cells after co-incubation with Der p 1 pulsed DCs from these two asthmatic groups. We also determined the mRNA expression of CCR4 ligands TARC/CCL17 and MDC/CCL22 in monocyte-derived DCs after Der p 1 pulsation. RESULTS: We performed flow cytometry analysis of CD4+ T cells from HDM-sensitive and non-atopic asthmatics, taken 24 and 48 h after co incubation with Der p 1-pulsed DCs. We demonstrated that after co-incubation, there was a significant increase in CCR3+ and CCR4+ CD4+ T cells from HDM sensitive asthmatics, which began to occur at 24 h and 48 h respectively, and corresponded to their expression at mRNA levels. In contrast, only CCR4 mRNA but not protein expression was increased in non-atopic CD4+ T cells. After Der p 1 pulsation, mRNA expression of CCR4-specific ligands (CCL17 and CCL22) was also markedly upregulated in HDM-sensitive DCs whereas only CCL17 gene expression was increased in non-atopic DCs. CONCLUSION: These data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure. PMID- 20364560 TI - IgE production in allergic asthmatic patients with different asthma control status. AB - BACKGROUND: Although much is known about the fact that IgE-mediated allergic inflammatory response contributes to airway inflammation, bronchial hyperresponsiveness, and asthma severity, little is known about the degree of IgE response in allergic asthmatics during treatment. OBJECTIVE: To determine the amount of total serum IgE among allergic asthmatic patients with various asthma controls. MATERIAL AND METHOD: A total of 190 non-smoking patients with allergic asthma were divided into three groups by using the asthma control definition according to the GINA 2006 criteria. There were 64 well-controlled, 88 partly controlled, and 38 uncontrolled. After study entry, patients underwent lung function test, methacholine challenge and skin prick test to establish allergic status. Peripheral venous blood specimens were collected to measure total IgE and absolute eosinophil numbers. The data are expressed as mean +/- SD. RESULTS: The logarithm of total serum IgE was significantly higher in subjects with uncontrolled allergic asthma than in those with well-controlled disease (p < .0001). IgE response in uncontrolled asthmatics was still high despite having been treated with ICS at a dose which was significantly high when compared with well-controlled subjects (1075.4 +/- 420 vs. 703.5 +/- 355, p < .0001). The logarithm of total serum IgE was associated with increased blood eosinophil counts (r = 0.25, p .0007) among three asthmatic groups and with decreased prebronchodilator FEV1 (r = -0.42, p = .0075) and PC20 (r = -0.36, p = .04) only in uncontrolled group. CONCLUSION: In allergic asthmatic patients with various disease control stages, there are differences in IgE immune response. Both high and non-suppressible total serum IgE response may be involved in the development of uncontrolled asthma. PMID- 20364561 TI - Clinical features and management of chronic thromboembolic pulmonary hypertension in Thai. AB - BACKGROUND: The incidence and clinical features of chronic thromboembolic pulmonary hypertension (CTEPH) in Thailand are unknown. This may be due to the difficulties in diagnosis, poor disease recognition and non-specific presenting symptoms and signs. With the new revolution of diagnostic tools and advanced knowledge about this condition, CTEPH is now discovered much more often. STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To evaluate common risk factors, symptoms, signs, commonly used investigations, treatment and results of treatment in Thai patients with CTEPH. MATERIAL AND METHOD: All patients with confirmed CTEPH diagnoses were selected for analysis in this study. We evaluated characteristics of patients with CTEPH at Siriraj hospital. All CTEPH patients' data included demographics, symptoms, signs, investigations, treatments, outcome and risk factors such as malignancy; previous deep vein thrombosis, immobilization, and congenital thrombophilia were recorded. STATISTICAL ANALYSIS: The descriptive statistics were used in this study. Categorical data and continuous data presented in term of percent and mean with standard deviation respectively. RESULTS: fourteen patients had confirmed diagnoses of CTEPH, five patients were male and 9 were female. The age of patients varied from 28 to 79 years-old. Mean age was 55-years-old. The most common presenting symptoms and signs were dyspnea (100%), followed by leg edema (78.6%), tachypnea (71.4%) and accentuation of pulmonic component of second heart sound (loud P2) (57.1%). At the time of diagnosis, four out of 14 patients were in NYHA class II, ten were in NYHA class III, and none of them was in NYHA class IV. Idiopathic CTEPH was found in 54.1% of patients. Congenital and acquired thrombophilia were the frequent risk factors found in our series. The most frequent radiographic abnormalities included enlarged pulmonary trunk, right atrium/right ventricle (RA/RV) dilatation, and cardiomegaly followed by prominent pulmonary trunk. Echocardiography findings were elevated right ventricular systolic pressure (RVSP); ranges varied from 60 mmHg to 137 mmHg (mean was 107.48 mmHg). The most common finding of arterial blood gas in APE patients was respiratory alkalosis with hypoxemia. The most frequent diagnostic tool used was ventilation-perfusion lung scan. Treatment of CTEPH patients was by anticoagulant, pulmonary thromboendarterectomy and inferior vena cava filter insertion. The success rate of surgical thromboendarterectomy in our institute was about 80%. CONCLUSION: Characteristics of CTEPH patients are unique and different from acute pulmonary embolism in aspects of clinical presentations, risk factors, investigation, common findings, treatment and outcome. PMID- 20364562 TI - Impact of bronchoalveolar lavage galactomannan on the outcome of patients at risk for invasive pulmonary aspergillosis. AB - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality among immunocompromised patients especially in neutropenic and patients treated with immunosuppressive drugs. New diagnostic tools have been developed to improve treatment and outcome. Compared with serum galactomannan, bronchoalveolar lavage galactomannan (BAL GM) detection has higher sensitivity (81% vs. 71%) and comparable specificity (87.6% vs. 89%). No study has correlated this test result to clinical outcome. MATERIAL AND METHOD: A prospective non-randomised study was conducted from March to December 2008 in adult patients who were suspected to have invasive pulmonary aspergillosis (IPA). Serum galactomannan levels were measured and bronchoscopy was performed to obtained BAL fluid for direct examination, culture, and measurement of galactomannan level. Response to treatment and mortality within 6-weeks of follow up were compared between positive and negative BAL GM groups. Factors influencing outcome were also analysed. RESULTS: There were 30 patients with 3 probable, 11 possible and 17 no IPA. Other causative organisms can be identified in 8 of 17 patients in the no IPA group. Overall, BAL GM at the 0.5 cut-off yielded a 46% positive result compared with 13% of serum GM (p = 0.005). There was no significant difference in positive result between BAL GM at 1.0 cut-off and serum GM. By using BAL GM as a mycological criteria, 54% of possible IPA was upgraded to probable IPA. Neither BAL GM nor serum GM results were associated with clinical response and mortality. Recovery of neutropenia was the only factor associated with response to treatment and outcome (p = 0.003). CONCLUSION: BAL GM detection has a higher positive rate than serum GM in patients at risk for IPA. It is helpful in diagnosis and categorization of IPA, but its impact on clinical outcome cannot be demonstrated in this study. PMID- 20364563 TI - The endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions. AB - BACKGROUND: Peripheral pulmonary lesions are technically challenging with conventional bronchoscopy in obtaining tissue diagnosis. The recently developed small-caliber ultrasonographic probe can be introduced via the working channel of a flexible bronchoscope to localize peripheral pulmonary lesions (PPLs) prior to transbronchial lung biopsy (TBLB). The endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) is a new diagnostic method for the diagnosis of pulmonary lesions in our center. OBJECTIVE: To evaluate the diagnostic yield of EBUS-TBLB in pulmonary lesions. STUDY DESIGN: A prospective cross-sectional study. MATERIAL AND METHOD: We enrolled 152 patients with pulmonary lesions that were beyond the segmental bronchus and had no evidence of endobronchial lesion, who underwent bronchoscopy in our center. With EBUS assisted, transbronchial lung biopsy was performed after localizing and measuring distance from the tip of bronchoscope to the lesion. The diagnostic yield was calculated. RESULTS: The pulmonary lesions were visible on EBUS image in 98.7% of cases. The overall diagnostic yield of EBUS-TBLB was 66.4%. The diagnostic yield in the infiltrative and mass lesions were 86.4% and 63.1%, respectively. The lesions which EBUS probe located within it were diagnosed by EBUS-TBLB about 74.8%. The benign and malignant lesions were diagnosed by EBUS-TBLB about 81.1% and 58.6%, respectively. The average EBUS time was 3.55 +/- 2.29 minutes. No complication of EBUS and transbronchial lung biopsy were observed in this study. CONCLUSION: EBUS-TBLB is a safe procedure for diagnosing pulmonary lesions. Our results indicate that the EBUS-TBLB improves the diagnostic yield compared to conventional brochoscopy. PMID- 20364564 TI - Impact of septic shock hemodynamic resuscitation guidelines on rapid early volume replacement and reduced mortality. AB - BACKGROUND: Septic shock is one of the most serious conditions associated with high mortality. We recently developed a modified septic shock management guideline focusing on rapid restoration of hemodynamics by using clinical endpoint. Our aim was to analyze patients' outcomes following the guideline implementation. MATERIAL AND METHOD: A retrospective review of hemodynamic data sheet and clinical outcomes of patients admitted to medical ICU and medical Wards and during June 2004 and February 2006. RESULTS: One hundred and four patients' records were retrieved. The patients' mean age was 62.5 +/- 18.6 year. Their mean APACHE II score were 24.9 +/- 6.7 and the overall mortality was 59%. Sixty eight patients (65.4%) underwent guideline directed therapy (guideline group). The guideline group received higher volume resuscitation from the first hour of resuscitation (1,016.3 + 675.0 ml vs. 521.4 + 359.2 ml, p < 0.001) to the forty eighth hour (10,096.9 +/- 3,256.1 ml vs. 8,067.3 +/- 2,591.9 ml, p = 0.006). More of them achieved the therapeutic goal within 6 hours (86.8% vs. 44.4%, p < 0.001) and their hospital mortality was lower (41.2% vs. 69.4%, p = 0.008). When analyzing differences between those who survived and those who died, more of the surviving patients underwent guideline directed treatment (79.5% vs. 55%, p = 0.012). They received higher volume replacement from the first hour to the end of the twelfth hour (first hour 1,098.0 +/- 723.0 vs. 660.9 +/- 478.9 ml, p < 0.001; the end of the twelfth hour 3,746.6 +/- 1,799 vs. 3,014.1 +/- 1,579.9 ml, p = 0.038) and more of them achieved the therapeutic goal within 6 hours (95.5% vs. 55%, p < 0.001). Multivariate analysis of factors associated with mortality disclosed APACHE II score, volume resuscitation more than 800 ml in the first hour and achievement of the therapeutic goal within 6 hours. CONCLUSION: Implementation of our modified septic shock guideline is associated with rapid initial volume replacement, prompt achievement of therapeutic goal and improved outcomes. Volume resuscitation greater than 800 ml in the first hour is associated with better survival. PMID- 20364565 TI - Microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero). AB - BACKGROUND: Several generic meropenem formulations have been approved by Thai Food and Drug Administration, Ministry of Public Health since 2008. Meropenem is a parenteral drug. Therefore, a study demonstrating a biological equivalence of generic meropenem is not required for drug registration in Thailand. The objective of the study was to determine microbiological equivalence of serum bacteriostatic and bactericidal activities of the sera from healthy volunteers receiving original meropenem (Meronem) and generic meropenem (Mero). MATERIAL AND METHOD: This was a randomized crossover study in 16 adult healthy volunteers. Each subject received one gram of Meronem and Mero in 50 ml of normal saline via intravenous infusion for 30 minutes. The blood samples were drawn at baseline prior to receiving the study drug, at 30 minutes after initiating infusion, and at 8 hours after initiating infusion. The serum bacteriostatic activity against E. coli ATCC 25922, K. pneumoniae, P. aeruginosa ATCC 27853 and A. baumannii was performed by disk diffusion. The serum bactericidal activity against E. coli ATCC 25922 was performed by Serum Bactericidal Titre. RESULTS: The average inhibition zone diameter of the serum samples from the subjects while receiving Mero against each tested organisms was < 1 mm smaller than that while receiving Meronem and such difference was not significantly different. All serum samples taken at 30 minutes after initiating Meronem and Mero had bactericidal titres against E. coli ATCC 25922 > or = 1:256. Only 3 serum samples taken from the subjects while receiving Mero at 8 hours had less bactericidal titre for 1-fold dilution when compared with that of Meronem. CONCLUSION: The sera from healthy volunteers receiving Meronem and Mero had microbiological equivalence in terms of serum bacteriostatic and bactericidal activities. PMID- 20364566 TI - Therapeutic equivalence of generic imipenem/cilastatin for therapy of infections at Siriraj Hospital. AB - BACKGROUND: Several generic imipenem/cilastatin formulations have been approved by Thai FDA and a generic imipenem/cilastatin (Yungjin) has been available in SirirajHospital since 2007. Since imipenem/cilastatin is usually given to the patients with serious hospital-acquired infections, the generic imipenem/cilastatin must be therapeutically equivalent to the original imipenem/cilastatin. The objective of the study was to compare effectiveness and safety of generic imipenem/cilastatin with original imipenem/cilastatin for therapy of infections in hospitalized patients at Siriraj Hospital. MATERIAL AND METHOD: Medical records of adult hospitalized patients at Siriraj Hospital who received imipenem/cilastatin at least 48 hours during June 2007 to September 2008 were reviewed. The effectiveness data of 300 patients who received original imipenem/cilastatin were compared with those of 300 patients who received generic imipenem/cilastatin in order to determine if a difference in composite favorable outcome of both formulations was within 10%. RESULTS: The demographics, clinical features of infections, site of infections, type of causative organisms and concomitant antibiotics of the patients in both groups were not significantly different. The overall favorable outcomes in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 65% and 58.7% respectively (absolute difference 6.3%, 95% CI -1.4% to 14%). Cure rates of infections in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 35% and 28.7% respectively (absolute difference 6.3%, 95% CI -1.1% to 13.7%). Super-infection rates in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 4.7% and 9% respectively (absolute difference -4.3%, 95% CI -8.5% to 0.3%). Mortality due to infections in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 18.3% and 21.3% respectively (absolute difference -3%, 95% CI -9.4% to 3.4%). Overall mortality in the original imipenem/cilastatin and the generic imipenem/cilastatin groups were 35.3% and 43% respectively (absolute difference -7.7%, 95% CI -15.3% to 0.1%). The occurrence of adverse events in the patients in both groups was not significantly different. CONCLUSION: Although the point estimate of composite favorable outcome of the patients who received generic imipenem/cilastatin (Yungjin) was < 10% of those who received original imipenem/cilastatin (Tienam), generic imipenem/cilastatin showed a trend for therapeutic non-equivalence to original imipenem/cilastatin because the upper limits of 95% confidence interval of differences of several important clinical outcomes were more than 10%. PMID- 20364567 TI - Hospital-acquired pneumonia and ventilator-associated pneumonia in adults at Siriraj Hospital: etiology, clinical outcomes, and impact of antimicrobial resistance. AB - BACKGROUND: Nosocomial pneumonia (NP), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is an important cause of morbidity and mortality in hospitalized patients. One of the factors contributing to a high mortality rate of HAP and VAP could be antibiotic resistance among the causative agents. OBJECTIVE: To determine prevalence of bacterial pathogens clinical features, risk factors of HAP and VAP, antimicrobial resistance among major respiratory pathogens, clinical implication of antimicrobial resistance, antimicrobial regimens used, and treatment outcomes of adult patients with HAP and VAP at Siriraj Hospital. MATERIAL AND METHOD: This was a prospective, hospital-based, active surveillance study on HAP and VAP in hospitalized adults at Siriraj Hospital from December 2007 to March 2009. The patients with HAP and VAP were followed prospectively until they expired or were discharged from the hospital. RESULTS: One hundred and forty-six adult patients were included. Seventy percent of the patients were males with the mean age of 70.8 years. HAP was accounted for 24.7% and VAP 75.3%. Most of the patients (82.9%) had late onset HAP or VAP with the median day of onset of pneumonia of 11 days. Two third of the patients were hospitalized in general medical wards. Bronchopneumonia was observed in 53.4% and multilobar pneumonia in 24.7%. A. baumanni was the most common isolated pathogen and 92.3% of them were multidrug-resistant (MDR) or pandrug-resistant (PDR). The other common isolated pathogens were K. pneumoniae, P. aeruginosa and methicillin-resistant S. aureus (MRSA). Carbapenem was the most commonly used initial antibiotic (45.9%) followed by colistin (21.9%) and cephalosporins (21.1%). The concordance of initial antibiotics was 58.9%. Antibiotics were modified 43.8% of the patients. Colistin was the most commonly used modified antibiotic followed by carbapenem. The modified antibiotics were concordant with isolated bacteria in 98.4%. The patients received mechanical ventilators in 81.5% with the median ventilator day of 10 days. At the initial response (72 hours after antibiotic therapy), an improvement was 56.8% and a mortality rate due to pneumonia was 14.4%. Death due to pneumonia at the end of treatment was 42.5%. The 30-day mortality from pneumonia was 45.9%. There were no significant differences in the outcomes of pneumonia between HAP and VAP. The factors associated with PDR-organisms were late-onset hospital-acquired pneumonia and previous carbapenem usage within 72 hours. Septic shock and bilateral lung involvement were significantly associated with unfavorable outcomes at 72 hours. Septic shock, severe sepsis, and previous carbapenem usage within 72 hours were significantly associated with mortality at the end of treatment and at 30 days after developing pneumonia. CONCLUSION: HAP and VAP remain to be very important hospital-acquired infections at Siriraj Hospital. The isolated pathogens are usually multidrug-resistant and the mortality rate remains high. The local data on prevalence of the isolated pathogens and their antibiotic susceptibility may help clinicians choose more appropriate initial antibiotics in order to improve the outcome and to decrease the emergence of resistant organisms. PMID- 20364568 TI - Clinical features and outcomes in patient with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment in Siriraj Hospital. AB - BACKGROUND: ANCA is detected in several vasculitic diseases, including drug induced systemic vasculitis: propylthiouracil (PTU), hydralazine, minocycline, penicillamine, allopurinol, procainamide, carbimazole, thiamazole, clozapine and phenytoin. All have been known to induce ANCA positive vasculitis in adult patients. OBJECTIVE: To study the clinical manifestation, renal pathology and outcome of patients with ANCA positive vasculitis associated with propylthiouracil treatment in Siriraj Hospital. MATERIAL AND METHOD: Retrospective study in 7patients with Graves' disease who were treated with propylthiouracil and developed ANCA-positive glomerulonephritis between 2000 2008. RESULTS: Seven cases with Graves' disease who received propylthiouracil whose ages were 43 +/- 14 years. The duration of propylthiouracil treatment was 68.5 +/- 39 months and the doses were 50-150 mg per day. Six cases had P-ANCA and one case had C-ANCA in the serum. Proteinuria ranged from 0.49-2.9 gram per day. Mean serum creatinine was 2.05 mg/dl with creatinine clearance of 44 +/- 35 ml/min. The propylthiouracil was withdrawn in every patient and corticosteroid was administered. Renal remission was found until 1 year of follow-up. CONCLUSION: ANCA positive glomerulonephritis associated with propylthiouracil is not uncommon. The average onset of glomerulonephritis is 2 years or more. The propylthiouracil dosage was not necessary high. Urinalysis and other glomerulonephritis symptoms should be screened for early diagnosis and appropriate treatment in patients treated with PTU. PMID- 20364569 TI - Malnutrition-inflammation score associated with atherosclerosis, inflammation and short-term outcome in hemodialysis patients. AB - BACKGROUND: Malnutrition-Inflammation Score (MIS) has been proposed as a new quantitative system for assessment of malnutrition and inflammation, which are common important risk factors for increased morbidity and mortality in maintenance hemodialysis (MHD) patients. OBJECTIVE: To determine the MIS and related it to the presence of atherosclerosis, and the morbidity and mortality rate. MATERIAL AND METHOD: The inflammatory and nutritional status in 100 MHD patients was evaluated by serum high-sensitivity C-reactive protein (hs-CRP), Subjective Global Assessment (SGA), and MIS. Atherosclerosis was defined by a history of cardiovascular disease or presence of carotid plaque by B-mode ultrasonography. Twelve-month prospective hospitalization and mortality rates were recorded. RESULTS: The MIS score was significantly higher in patients with atherosclerosis (5.5 +/- 2.3 vs. 3.0 +/- 1.7, p = 0.003) and modestly correlated with serum ferritin level (r = 0.304, p = 0.03), but did not correlated with hs CRP. The SGA was not associated with hs-CRP level and atherosclerosis. Over a 12 month follow-up period, 4 patients died and 28 were hospitalized at least once. Compared to the survivor group, MIS in the deceased group was significantly higher (8.0 +/- 1.4 vs. 5.1 +/- 2.3, p = 0.01) while SGA, hs-CRP and other biochemical markers were not significantly different. The Receiver Operating Characteristics Curves for the prediction of 1-year mortality from the MIS score identified the optimal cut-off value of 7.5 with sensitivity of 75% and specificity of 88%. There was no association between MIS or SGA and hospitalization. CONCLUSION: MIS is a useful tool for the assessment of malnutrition and inflammatory status. It is superior to the conventional SGA as a predictor of short-term outcome in MHD patients. PMID- 20364570 TI - A method comparison study of flow cytometry and cytomorphology to determine the percentages of blasts in patients with acute leukemia after induction and consolidation chemotherapy. AB - BACKGROUND: Enumeration of blasts in the bone marrow is an essential component in the diagnosis and treatment of acute leukemia. The current gold standard method is based on a morphologic counting of 500 marrow nucleated cells despite its operator dependence and inter-observer variability. OBJECTIVES: To compare the percentages of marrow blasts derived from two different approaches comprising routine morphology-based manual counting and flow cytometric analysis. MATERIAL AND METHOD: Fifty-five marrow samples were collected from 38 acute leukemia patients (36 AML and 19 ALL) after hematologic recovery from chemotherapy. The blast percentages were enumerated manually and by flow cytometer using CD45 and side scatter gates. RESULTS: A good correlation was found in the overall 55 samples (r = 0.829) and 36 AML samples (r = 0.86). The blast percentages derived from flow cytometer were higher than from morphologic counting in 46 samples (83.6%). Using a cut-off point of < 5% blasts to define complete remission (CR), 48 cases (87%) were classified as morphological CR (83% CR in AML and 95% CR in ALL). By flow cytometry, only 24 cases (44%) were in CR (28% CR in AML and 74% CR in ALL). The results from each method were concordant in determining CR in 27 samples (49%), with a kappa value of 0.07 for overall samples, 0.057 for AML and 0.096 for ALL samples. CONCLUSION: A good correlation between the percentages of blasts achieved by either method was demonstrated, particularly in AML samples. Discordant results occurred when <5% blasts were used as a cut-offpoint to determine CR. Both methods should be complementarily performed to ensure a truly complete response to chemotherapy. The method discrepancy should be further investigated in order to increase the level of confidence in CR status. PMID- 20364571 TI - Incidence and risk factors of relapses in idiopathic autoimmune hemolytic anemia. AB - BACKGROUND: Patients with idiopathic autoimmune hemolytic anemia (AIHA) of warm antibody type usually respond to corticosteroid therapy. However a proportion of patients will have disease relapse after steroid-induced remission. OBJECTIVE: To assess the incidence and the possible risk factors of the relapse in a cohort of patients with idiopathic AIHA. MATERIAL AND METHOD: We conducted a retrospective and prospective study of 34 idiopathic AIHA patients regularly followed at the Division of Hematology during January 1973 to December 2006. The medical records were reviewed for active hemolytic events and relapses, episodes of infections, pattern of corticosteroids administration and tapering. Types and subtypes of autoantibodies were studied by column agglutination test (the "gel test"). RESULTS: One patient with cold agglutinin disease was excluded, leaving a total of 33 patients (24 with warm type, 9 with mixed warm and cold type AIHA) in the study. The incidence of relapse was 1.157 episodes/person/year. The mean duration of relapse after remission was 23 months. Episodes of recurrent hemolysis were more frequent when corticosteroid administration was tapered from high to low dose (10 mg/day of prednisolone) within two months compared with a longer than two-month tapering (38 vs. 11 episodes; p < 0.01). In addition patients receiving continuing low dose of corticosteroids (< or = 10 mg/day of prednisolone) for > 6 months had lower incidence of relapse and longer duration of remission than those with discontinuing the medication within 6 months (0.443 vs. 1.911 episodes/person/year, p < 0.01; 37.4 vs. 10.6 months, p < 0.01). Episodes of recurrent hemolysis were more frequently observed in patients with events of infection than those without infections (mean 7.69 vs. 2.81, p = 0.032). Types and subtypes of autoantibodies did not seem to influence relapse in AIHA. CONCLUSION: Short duration of maintenance and rapid tapering of corticosteroids and infections are possible risk factors of relapses/recurrent hemolysis in idiopathic AIHA. PMID- 20364572 TI - Establishment of the Thai version of National Institute of Health Stroke Scale (NIHSS) and a validation study. AB - BACKGROUND: The National Institute of Health Stroke Scale (NIHSS) is a well validated stroke severity assessment scale. The scale is used to assess neurological deficits, progression and degree of recovery in acute stroke settings. To date, no Thai version exists. OBJECTIVE: This study aimed to adapt and validate a Thai version of the NIHSS (NIHSS-T). MATERIAL AND METHOD: A cross cultural adaptation of the NIHSS was developed according to the methods recommended by the International Quality of Life Assessment Project Group. Forward and backward translations were performed. A final version of the NIHSS-T was validated against initial MRI infarction volume and modified Rankin Scale (mRS) at 3 months in a consecutive series of acute stroke patients. The patients were prospectively evaluated by 3 different types of health care providers: 2 stroke fellows, 2 internists, and 2 stroke nurses. Mean NIHSS-T scores from all raters were used in the analysis. RESULTS: The study included 32 acute ischemic stroke patients with a mean age (+/- SD) of 64.53 +/- 14.97 years of age. Men comprised 71.9%. Mean NIHSS-T score (+/- SD) was 7.49 +/- 7.02. Intra-observer reliability demonstrated a high agreement with an intraclass correlation (ICC) of 0.98, 0.98, 0.96, 0.98, 0.90 and 0.98 for 2 stroke fellows, 2 internists and 2 stroke nurses respectively. Inter-observer reliability between 6 raters was excellent, i.e.; ICC, 0.99 (0.98, 0.99). Spearman rank correlation coefficients between the initial NIHSS-T score versus initial MRI lesion volume and mRS at 3 months were 0.53 and 0.69 with a p-value of 0.002 and < 0.001 respectively. CONCLUSION: The Thai version of NIHSS is valid for assessing acute stroke severity. The scale is also reliable when administered in a Thai-speaking setting by trained healthcare professionals. PMID- 20364573 TI - Drug use evaluation of statins at Siriraj Hospital, 2008. AB - Statins are commonly used for lipid reduction. There is no significant difference in the efficiency of each type of statins. The study of statins' efficacy shows that only generic simvastatin is cost-effective in coronary heart disease prevention. OBJECTIVE: To determine the use and appropriateness of usage of statins in out-patients attending Siriraj Hospital in 2008. MATERIAL AND METHOD: Medical records of all patients in Siriraj Hospital who received statins from January 1st to December 31st, 2008 were reviewed. The appropriateness of statins used was analyzed in 247 medical records based on number of risks and 10-year risk. RESULTS: There were 105,950 patients who received statins with total value of 308 million baht in 2008. The major usages of statins were simvastatin (65%), atorvastatin (12%) and rosuvastatin (6%). However, the costs of statins were 9%, 42%, and 20% for simvastatin, atorvastatin and rosuvastatin, respectively. Analysis of 247 medical records of the patients who received statins showed that statins were appropriately used in 19.4% of cases. Inappropriate use of statins was due to not starting drugs treatment with simvastatin, or shifting from simvastatin to other statins inappropriately. CONCLUSION: Inappropriate use of statins at Siriraj Hospital is very common. Interventions for promoting more appropriate use of statins should be implemented. PMID- 20364574 TI - Diagnosis of corticosteroid insufficiency in Thai patients with septic shock. AB - BACKGROUND: The reported incidence of critical illness-related corticosteroid insufficiency (CIRCI) varies widely, depending on the patient population studied and the diagnostic criteria used. Surviving Sepsis Campaign guidelines suggest that corticosteroid therapy should be considered for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors, regardless of any results of diagnostic tests. However, steroid treatment may be associated with an increase risk of infection. This study aims to identify the best diagnostic tool for predicting responsiveness to corticosteroid therapy in Thai septic shock patients with poorly responsive to fluid resuscitation and vasopressors. MATERIAL AND METHOD: Twenty-nine septic shock patients who were poorly responsive to fluid therapy and vasopressors were studied. A baseline serum total cortisol was measured in all patients and then 250 mcg corticotropin was injected to patients. Cortisol level was obtained 30 and 60 minutes after injection. All patients were given hydrocortisone (100 mg i.v., then 200 mg i.v. in 24 hrs for at least 5 days). Patients were considered steroid responsive if vasopressor agent could be discontinued within 48 hrs after the first dose of hydrocortisone. RESULTS: Hospital mortality was 62% in which 45% of the patients were steroid responsive. Baseline serum cortisol was 27.6 +/- 11.4 microg/dl in the steroid-responsive patients compared with 40 +/- 16.9 microg/dl in the steroid-nonresponsive patients (p = 0.03). The area under the ROC curves for predicting steroid responsiveness was 0.72 for baseline cortisol level. Serum cortisol level of 35 microg/dl or less was the most accurate diagnostic threshold to determine hemodynamic response to hydrocortisone treatment (p = 0.04). Using baseline cortisol level of < or = 35 microg/dl to diagnose adrenal insufficiency, the sensitivity was 85%, the specificity was 62% and the accuracy was 72%. A use of (delta cortisol) showed sensitivity of 50%, specificity of 30% and accuracy of 41%. CONCLUSION: Baseline cortisol level < or = 35 microg/dl is a useful diagnostic threshold for diagnosis of steroid responsiveness in Thai patients with septic shock and ACTH stimulation test should not be used. PMID- 20364575 TI - A rare occurrence of hairy cell leukemia in the Thai population: a case report. AB - Hairy cell leukemia (HCL) has been mainly reported from the Western countries. Herein we describe a case of HCL diagnosed in a Thai patient. A 36-year-old man presented with abdominal discomfort, frequent gum bleeding and significant weight loss for 2 months. Physical examination revealed moderate anemia, petechial hemorrhage on the extremities and an enlarged spleen down to the umbilicus. No hepatomegaly or lymphadenopathy was detected. Complete blood counts revealed a hemoglobin (Hb) of 6.6 g/dL, a white blood cell (WBC) count of 1.6 x 10(9)/L (neutrophil 16%, lymphocyte 71%, monocyte 11%, atypical lymphocyte 1%), and a platelet (PLT) count of 17 x 10(9)/L. Abnormal large mononuclear cells with villous projections were seen in the blood smear. Although bone marrow (BM) aspiration resulted in a dry tap, abnormal lymphocytes with villous projections could again be identified in the touch preparation. Flow cytometric analysis showed a distinct population above the normal lymphocyte region on CD45/SSC gates with a strong expression of CD19, CD20, CD22, CD25, CD11c, and kappa. CD5, CD23, CD10, CD4, and CD8 were all negative. BM biopsy was consistent with HCL. The patient was treated with splenectomy followed by 8 cycles of fludarabine and cyclophosphamide chemotherapy. At 21 months after diagnosis, the patient was doing well with a Hb of 16.9 g/dl, a WBC count of 6.8 x 10(9)/L, neutrophil 49.9%, lymphocyte 39.6%, monocyte 8.6%, and a PLT count of 329 x 10(9)/L). No abnormal lymphoid cells were detected in the blood smear. This present report represents the first Thai HCL case that was immunophenotypically confirmed by flow cytometry and successfully treated at Siriraj Hospital. PMID- 20364576 TI - [Epigenetic activation of IGF2 during cellular senescence]. AB - OBJECTIVE: Epigenetic regulations of insulin-like growth factor 2 (IGF2) were observed during cellular replicative senescence and premature senescence induced by hydrogen peroxide of human embryonic lung fibroblasts (HEFs). METHODS: The mRNA level of IGF2 was detected by Q-PCR. The methylation status in the promoter region was observed by methylation-specific PCR. The histone modifications was detected by chromatin immunoprecipitation-Q-PCR assay, including acetylation for H3, H4 and methylation for H3 ( Lys4) and H4 (Lys20). RESULTS: In the process of cellular senescence, the mRNA level of IGF2 increased in both mid-aged and replicative senescent cells, but increased obviously in premature senescent cells compared with that of young cells. In the promotor region from -658 bp to -456 bp, the methylation level for IGF2 was detected only in replicative senescent cells. About the main histone modifications, IGF2 in the region (-856 bp - -634 bp) was H4 acetylation and H3K4 methylation in replicative senescence, while in the region (+9 bp - +145 bp) was H3K4 and H4K20 methylation in replicative senescence and H3K4 methylation in premature senescence. CONCLUSION: The histone modifications take part in regulating the mRNA expression for IGF2 during cellular senescence and different mechanisms exist between two types of senescence. PMID- 20364577 TI - [Reproductive toxicity of male rats exposed to two isomers of bromopropanes]. AB - OBJECTIVE: To study the reproductive toxicity of male rats exposed to 1 bromopropane and 2-bromopropane and to explore the toxic mechanism of two isomers. METHODS: 18 SPF SD male rats were randomly divided into 3 groups of 6 each, respectively. The groups were exposed to corn oil, 1-BP (1 g/kg) and 2-BP (1 g/ kg) for 7 days by intraperitoneally injection. Trait of reproductive organs, sperm characteristics, testicular histological and apoptotic findings and the lipid peroxidation in the testicular and epididymal tissue were determined. RESULTS: Results showed that treatment with bromopropanes induced reduction in sperm concentration and increments in abnormalities of sperm injuries to sperm quality. In addition, 1-BP increased GR activity (7. 42 +/- 2.98 vs. 4.25 +/- 1.18, P < 0.05) in testis, and SOD activity (91.87 +/- 3.93 vs. 80.59 +/- 9.92, P < 0.05) and MDA level (0.49 -/+ 0.20 vs. 0.39 +/- 0.08, P < 0.05) in epididymis. 2-BP decreased the GSH lever (6.35 +/- 1.86 vs. 10.89 +/- 3.69, P < 0.05) and increased the MDA level (0.42 +/- 0.07 vs. 0.24 +/- 0. 11, P < 0.05; 0.48 +/- 0.08 vs. 0.39 +/- 0.08, P < 0.05) in epididymis and testis, decreased GST ( 53.21 +/- 9.60 vs. 61.98 +/- 10.41, P < 0.05) and GR activity (2.48 +/- 1.21 vs. 7.75 +/- 8.56, P < 0.05) in epididymis. There were no histopathological changes in treatment with 1-BP rats, except that retained and elongated spermatids near basement membrane at the spermatogenesis cycle were found. Whereas, treatment with 2-BP induced vacuolation, degeneration and necrosis in seminiferous tubules. Paralleling with testicular lesion, treatment with 2-BP increased the total apoptotic cells per tubule, the percentage of apoptotic cells and apoptotic index significantly, comparing with control (17.72 +/- 4.59 vs. 5.92 +/- 1.05, P < 0.05; 0.34 +/- 0.14 vs. 0.10 +/- 0.02, P < 0.05; 6.64 +/- 3.40 vs. 0.59 +/- 0.20, P < 0.01). As compring with 1-BP group, exposed to 2-BP increased the percentages of TUNEL-positive tubules and apoptotic cellindex (0.34 +/- 0. 14 vs. 0.12 +/- 0. 03, P < 0.05; 6.64 +/- 3.40 vs. 0.76 +/- 0.21, P < 0.01). In addition, 2-BP group increased the proportion of apoptotic germ cells and the number of active caspase 3-positive cells per tubule, compared with 1-BP and control (P < 0.01, P < 0.01; P < 0.01, P < 0.01). CONCLUSION: This study indicates that bromopropanes can cause reproductive disorder in male rats, the rats treatment with 2-BP had more toxicity than that with 1-BP, and it might have different toxic mechanism between two isomers. PMID- 20364578 TI - [Study on the levels of the bisphenol A, octylphenol, 4-nonylphenol in serum of precocious girls]. AB - OBJECTIVE: To investigate the role of bisphenol A (BPA), octylphenol (OP), 4 nonylphenol(4-NP) causing precocious girls. METHODS: The blood samples were collected from 110 cases of precocious girls and 100 cases of normal girls. The concentrations of BPA, OP, 4-NP in serum samples were measured by using high performance liquid chromatography (HPLC), the volume of the uteruse and ovary, the content of estradiol (E2) were determined at the same time. The contents of BPA, OP, 4-NP in blood serum of precocious girls and the indices of the target organs were analyed by using correlation. RESULTS: BPA and, OP were detected in blood serum for 40.9% and 33.6% of precocious girls respectively, BPA and OP were detected for only 2% and 5% in normal girls respectively, 4-NP was detected for 24.54% of precocious girls and 3% of normal girls. The ratio of BPA, OP, 4-NP in blood serum of precocious girls was higher than normal girls respectively (P < 0.01), BPA in blood serum of precocious girls patients was positive correlation with the volume of the uterus (r = 0.557, P < 0.05), and positive correlation with volume of the ovary (r = 0.469, P < 0.01). OP in blood serum of precocious girls patients was positive correlation with the volume of uterus (r = 0.576, P < 0.05), positive correlation with volume of ovary (r = 0.676, P < 0.01). CONCLUSION: Precocious girls patients were contaminated more severely than normal girls, and BPA, OP could influence the volume of the uterus and ovary, so it had some relationship with cause of precocious girls. PMID- 20364579 TI - [Effect of DNA polymerase beta on repair of DNA damage induced by benzo(a) pyrene]. AB - OBJECTIVE: To clarify the relationship between the expression of pol beta and DNA damage /repair induced by Benzo(a)pyrene (BaP). METHODS: pol beta wild-type cells (pol beta +/+), pol beta null cells (pol beta -/-) and wild-type pol beta overexpressed cells (pol beta oe) which had the same genetic background were studied. Firstly, RT-PCR and Western blot targeting to pol beta were carried out to measure the expression of pol beta mRNA and protein in above three kinds of cells, then MTT test and single cell gel electrophoresis (comet assay) were used to compare cell viability and DNA damage/repair of the three kinds of cells when exposed to BaP. RESULTS: There was pol beta deletion in pol beta -/- cells and the level of pol beta mRNA and protein in pol beta oe cells was twice higher than that in pol beta +/+ cells. BaP could induce DNA damage and reduce cell viability, when compared with pol beta +/+ cells, IC50 of pol beta -/- cells was remarkably lower, DNA was prone to damage and more difficult to be repaired, on the other hand, IC50 of pol beta oe cells was obviously higher and the damage effect on DNA was weaker and prone to be repaired. CONCLUSION: Pol beta played an important role in the repair of DNA damage induced by BaP, deficiency of pol beta could decrease the DNA repair capability of cells, and overexpression of pol beta could help cells response to DNA damage and protect cells from death in a certain degree. PMID- 20364580 TI - [Effect of sucrose on glucose and lipid metabolism and the pathological changes of liver and pancreas in GK and Wistar rats]. AB - OBJECTIVE: To study the effect of sucrose on glucose and lipid metabolism and the pathological changes in liver and pancreas of diabetic and normal rats. METHODS: 32 Wistar rats and 32 GK rats were randomly divided into W (Wistar), WS (Wistar + 30% sucrose), G (GK) and GS (GK +30% sucrose ) groups. There was 30% sucrose in the drinking water for WS and GS groups and no sucrose in the drinking water for W and G groups. The metabolism of glucose and lipid and the pathological changes of liver and pancreas were observed at the 2nd, 4th, 6th and 10th week of the experiment respectively. RESULTS: The body weight and serum TG of WS group increased gradually after drinking water with sucrose, while serum Glu and TC were not changed. There were some pathological lesions in the liver and pancreas of WS group, and the occurrence of lesions in pancreas was earlier than that in liver. Besides what discovered in WS group, serum TC of GS group decreased initially and then gradually recovered, while serum Glu decreased initially then gradually increased. In comparison with WS group, the occurrence of pancreas and liver injuries in GS group was earlier and severer than those in WS group. CONCLUSION: Sucrose is harmful for GK and Wistar rats, and could induce or exacerbate the disorder of glucose and lipid metabolism, the pathological lesions of liver and pancreas, and showed a time-response relationship. PMID- 20364581 TI - [Effect of copper intake and copper-zinc ratio on rat lipid peroxidation in copper deficiency]. AB - OBJECTIVE: To study the relations among the copper concentration, the copper-zinc ratio (Cu/Zn) and the biomarkers of lipid peroxidation by controlling the level of copper intake in copper deficiency, to analyze the effect of trace element copper on the rat lipid peroxidation. METHODS: Determine the content of copper in blood and the activity of superoxide dismutase (SOD), glutathione peroxidase (QSH Px) and catalase (CAT) and the content of malondialdehyde (MDA), carrying out the relevant research. RESULTS: The rats were treated with copper gluconate (Cu-G) in different doses in the case of insufficient copper intake, the copper concentration in the blood of each group rats presented irregular fluctuate, while the copper-zinc ratio (Cu/Zn) showed a ascending trend following the increase of copper intake, and the results have statistical significance (P < 0.01). In the status of copper deficiency, the SOD activity is lower than the normal level, and then presented a rise trend with the increased of copper intake that is, the ratio of copper-zinc (Cu/Zn). The content of MDA is higher than the normal level, and the content of MDA decreased with the increased of copper intake and the Cu/Zn ratio, and maintained at a relatively low level. The decreased of Cu/Zn ratio could induce the decrease of the CAT activity in the rat blood, while there were no linear correlation be found between them. And no significant effect on the GSH-Px activity in the rat blood in inadequate of copper intake. CONCLUSION: In copper deficiency, the SOD activity in the rat blood would be lower than the normal level and the content of MDA would increase in rat blood, while with the increase of Cu/Zn ratio, the SOD activity increased gradually, and the content of MDA dropped to a lowed level. While the insufficient intake of copper could induce a increase of the CAT activity in blood and no effect on GSH-Px. PMID- 20364582 TI - [Effect of compound coarse grain food on insulin resistance and expression of PPARgamma in rat]. AB - OBJECTIVE: To explore the effect of compound coarse grain food on insulin resistance (IR) in rats. METHODS: Forty Sprague-Dawley rats were randomly divided into normal control group (n=10) and model group (n=30), provided regular diet and high fat diet separately. After 6 weeks, the model group were divided into high fat diet group, rice flour group and coarse grain group, and provided the corresponding feed. After feeding 9 weeks, the fasting blood glucose, insulin and the expression of PPAR-gamma mRNA in rats were measured. RESULTS: IR was successfully induced by 6-weeks high fat diet. The body weight and insulin resistance index (HOMA-IR) in coarse grain group were significantly lower than high fat diet group and rice flour group. The expression of PPAR-gamma mRNA in coarse grain group was significantly higher than other three groups (P < 0.05). CONCLUSION: The coarse grain food can reduce the concentration of blood glucose and insulin in rat with insulin resistance induced by high-fat dietary, and improve insulin sensitivity. The possible mechanism is the over-expression of PPAR-gamma. PMID- 20364583 TI - [Comparative research on digestibility of lysine-rich genetically modified rice and its parental rice in Wuzhishan mini-pig]. AB - OBJECTIVE: To study the digestibility of protein and amino acids in lysine-rich genetically modified (GM) rice and its parental rice. METHODS: Eight Wuzhishan Mini-pig Inbred-line as the experimental animals, T-cannulas were equipped at their terminal ileums by surgical operation. Six of them, which were well-healed and with good appetite, were fed with lysine-rich genetically modified rice and its parental rice, and digesta of each pig was collected and analyzed respectively for comparing their apparent digestibility (AD) and true digestibility (TD). The endogenous amino acids losses were determined by casein diet method. RESULTS: The AD and TD of protein are very similar in the two types of rice. There are no statistical differences in the AD of all amino acids except for Cysteine, and there are no statistical differences in the TD of all 18 amino acids. CONCLUSION: The lysine-rich GM rice has no statistical difference with its parental rice in terms of protein and amino acid digestion and absorption in Wuzhishan mini-pigs. PMID- 20364584 TI - [Analysis of 16S rDNA sequence of Cronobacter spp]. AB - OBJECTIVE: To analyse the sequence of 16S rDNA of twenty-nine Cronobacter spp. strains isolated from food as well as two type strains. METHODS: Using polymerase chain reaction to obtain the sequences of 16S rDNA of all strains. The multiple cluster analysis and phylogenetic analysis of them were studied by BioNumerics software. RESULTS: All strains, except ATCC51329 and ES 014, were clustered with the Cronobacter spp. type strain ATCC29544. The Cronobacter spp. type strain ATCC51329 and ES 014 belonged to a different branch. From the sequence analysis of 16S rDNA, all these isolates of Cronobacter spp. except ES 014 could be identified accurately by gene analysis. CONCLUSION: All Cronobacter spp. strains isolated from food were identified on genetic level. The phylogenetic relationships among related Cronobacter spp. isolates were studied. PMID- 20364585 TI - [Growth inhibition and apoptosis-inducing effects of phytic acid in human gastric carcinoma cells]. AB - OBJECTIVE: To explore the growth inhibition and apoptosis-inducing effects of phytic acid in human gastric cancer SGC-7901 cells. METHODS: The growth inhibition action of phytic acid on SGC-7901 cells was examined by MTT assay. AO/EB fluorescence staining and DNA ladder assay were applied to study the proapoptosis effects of phytic acid. The expression of apoptosis relative proteins, P53, were analyzed by using immune histochemisty method. RESULTS: Phytic acid treatment significantly inhibited the growth of human gastric cancer cell SGC-7901 and markedly caused their apoptosis following downregulation of P53 protein expression. CONCLUSION: The downregulation of apoptosis relative protein P53 expression was the possible mechanism of phytic acid induced growth inhibition and apoptosis in SGC-7901 cells. PMID- 20364586 TI - [Association between aldehyde dehydrogenase-2/cytochrome P450 2E1 genetic polymorphism and habit of alcohol drinking and the susceptibility of hepatocellular carcinoma]. AB - OBJECTIVE: To study the relationship between aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) gene polymorphism and alcohol drinking habit with the susceptibility of hepatocellular carcinoma( HCC). METHODS: 300 cases of HCC and 292 controls were genotyped for the ALDH2 and CYP2E1 polymorphisms by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequencies of ALDH2 and CYP2E1 variant genotypes in cases and controls were 50.3%, 48.0% and 32.3%, 32.9%, respectively. There was no significant difference of ALDH2 and CYP2E1 genotypes distribution between cases and controls (P > 0.05). The risk for liver cancer was 3.334 times higher in alcoholics ( > or =3 times drinking per week) with ALDH2 * 2 genotype than that that in cases carrying ALDH2 * 1 genotype while drinking less than 3 times per week (95% CI = 1.746 - 6.406) , and the risk for liver cancer was 1.803 times higher in alcoholics ( > or =3 times drinking per week) with CYP2E1c2 genotype than that in cases carrying CYP2E1cl genotype while drinking less than 3 times per week (95% CI = 0.974 - 3.336). Haplotype of the two genotypes increased liver cancer risk to 1.200 folds (95% CI = 0.730 - 1.972), and interaction between drinking and genotypes increases risk of liver cancer to 1.816 folds (95% CI = 0.985 - 3.348). CONCLUSION: ALDH2 or CYP2E1 genotypes alone render no significant risk for HCC, while frequent alcoholic consumption together with ALDH2 or CYP2E1 variant genotypes are associated with risk of hepatocarcinogenesis, suggesting a gene-environment interaction in increasing risk for HCC among Guangxi residents. PMID- 20364587 TI - [Determination and status quo survey of phathalic acid esters in air of plastic production logistics by GC-MS]. AB - OBJECTIVE: To establish GC-MS method for the determination of phathalic acid esters (PAEs) in the air of plastic production logistics, and conduct a status quo survey of PAEs pollution in occupational environments basing on it. METHODS: The determination method was established according to the Monitor Investigating Guidelines on Poisons in Workplace Air, and then used to determine samples collected to carry out an on-the-spot investigation. RESULTS: Calibration curves of the six PAEs were proved to be all linear in the range of 2-1000 ng/ml, equivalent to 0.67-333 microg/m3 in the air considering 3 L air sample was collected. The sensitivities were high with all limits of detection lower than 1 ng/ml, i.e., the minimum detectable concentrations of the six PAEs were all lower than 0.33 microg/m3. Intra-day precision and accuracies were all good, with relative standard deviation in the range of 3.0%-7.8% and recoveries in the range of 93.1%-105.1% respectively. And inter-day precision and accuracies were 3.4% 9.9% and 93.4%-106.4% correspondingly. The eluting efficiency was 92.9%-97.9%, and the sampling efficiencies were nearly 100%. The breakthrough capacities were all larger than 1.4 mg. And samples could be stored stably at room temperature for 7 days. The selectivity of this method was good. Results of status quo survey indicated that the PAEs pollution in the air of plastic production logistics was not serious, and no obvious clinical symptoms and signs were found in those occupationally-exposed workers. CONCLUSION: This method meets the demand of the Monitor Investigating Guidelines on Poisons in Workplace Air, and thus then could be applied to determine PAEs in the air of plastic production logistics. PMID- 20364588 TI - [Effects of airborne fine particulate matters on human immunological indicators]. AB - OBJECTIVE: To explore effects of airborne fine particulate matters on human immunological indicators. METHODS: All subjects were measured the level of PM2. 5 individual exposure with personal sampling devices. Serum immunological indicators, such as WBC, NE, NE%, Ly, Ly%, CD4+, CD8+, CD4+ / CD8+, IgA, IgM, IgG and IgE were detected through enzyme-linked immunosorbent assay. Then, comparing the difference of PM2.5 exposure and immunological indicators between two groups. RESULTS: For the level of PM2.5 daily exposure, traffic policemen (115.4 +/- 46.2) microg/m3) was significantly higher than residents ((74.9 +/- 40.1) +/- g/ m(-3)). And there was also significant difference in some immunological indicators, such as Ly%, CD4+, CD8+, IgM, IgG, IgE, CC 16 and CRP, between two groups. CONCLUSION: Long-term high level of airborne fine particulate matters exposure may change some blood immunological indicators, affect the health of the immune system. PMID- 20364589 TI - [Effect of fluoride on human hypothalamus-hypophysis-testis axis hormones]. AB - OBJECTIVE: To study of endocrine disturbing effect of fluoride on human hypothalamus-hypophysis-testis axis hormones. METHODS: Sunying County, Kaifeng City was selected as polluted district which the fluoride in drinking water was 3.89 mg/L, and Shenlilou county was selected as control district which the fluoride was less than 1.0 mg/L. 150 individual lived there more than 5 years were srlected randomly. And investigated by medical examination, then blood and urine sample were collected, and the serum level of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) were measured by RIA method, and the urine level of fluoride were measured. Other than that, the concentration of fluoride in the water, food, soil and air were detected by the standard methods. RESULTS: The concentrations of fluoride in the water, food and soil of the fluoride polluted district were significantly higher than those of control district (P < 0.05), and the concentration fluoride in the air of two district were not found. There was no significant difference of serum level of GnRH between fluoride polluted district and control district (P > 0.05). The serum level of LH in men of fluoride polluted district was significantly higher than that of control group (P < 0.05), and the serum level of T in men of fluoride polluted district was significantly less than that of control group (P < 0.05). There was no significant difference of serum level of LH between fluoride polluted district and control district (P > 0.05), and the serum level of T in women of fluoride polluted district was significantly higher than that of control group (P < 0.05). There was no significant difference of serum level of E2 between fluoride polluted district and control district (P > 0.05). CONCLUSION: Fluoride could effect hormone levels of each layer of the hypothalamus-hypophysis testis axis, and show the reproductive endocrine disturbing effects. The reproductive endocrine disturbing effects of male maybe more severe than those of female. PMID- 20364590 TI - [Effect of soy isoflavones on peri-menopausal symptom and estrogen]. AB - OBJECTIVE: To study the effect of soy isoflavones (SI) on improving peri menopausal symptoms and the secretion of estrogen. METHODS: Fifty women accompany with peri-menopausal symptoms were single-blindly randomized into two groups, the SI group with a daily 120 mg/d of soy isoflavones for eight weeks and the control group with placebos. Serum 17 beta-estrodiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), progesterone, testosterone and prolactin (PRL) were assessed at baseline and after 8 weeks of observation. The symptoms, such as the frequency of hot flash and sweating, insomnia and Kuppermann scores were observed. RESULTS: By the end of the trial, BMI was significantly increased (P < 0.05). Hot flashes, Kuppermann scores and other index were significantly decreased (P < 0.01), and E2, progesterone and testosterone were significantly increased (P < 0.01 or P < 0.05). FSH was significantly decreased in SI group (P < 0.01). In comparison with control group, hot flash frequency, vaginal dryness, Kuppermann scores and other index were significantly decreased in SI group, E2, PRL and testosterone were also significantly increased in SI group and FSH, 2H were decreased. CONCLUSION: Menopausal symptoms and the secretion of estrogen were improved in peri-menopausal women on a daily dosage of 120 mg of soy isoflavones. PMID- 20364591 TI - [Prevalence of equol producer phenotype and its relations to lifestyle factors and dietary intakes among lifestyle factors and dietary intakes among healthy Chinese adults in Beijing]. AB - OBJECTIVE: To investigate the prevalence of equol producers and the physiological range of urinary equol excretion, and also to evaluate relations between equol phenotype and lifestyle among Chinese adults in Beijing. METHODS: 100 male and 100 female adults participated in a cross-sectional study and provided twice 1d urine samples on regular diet and after 3d soy isoflavone challenge respectively. A health and demographics questionnaire, and 2d food record were completed before the urine collections. Isoflavones and their metabolites in urine were measured to determine equol phenotype by HPLC. RESULTS: The physiological range of 24h urinary equol excretion was 0-76.56 micromol/24h, and the percentage of the equol producer phenotype was 26.8% on regular diet and 60.4% after soy isofavone challenge, respectively. There was no indication that habitual consumption of soy foods is associated with the equol producer phenotype. The correlations of isoflavone intake from 2d food record with those from urinary isoflavone levels were 0.58 for total isoflavones, 0.49 for daidzein, 0.56 for genistein, and 0.50 for glycitein (P < 0.01). CONCLUSION: About one fourth of Chinese adults in Beijing were detected equol excretion in urine under the usually lifestyle. However, equol_producing potential was higher. PMID- 20364592 TI - [Growth and anemia status investigation of 0-2 years infant and child in poor rural areas of Guangxi autonomous region]. AB - OBJECTIVE: To investigate and analysis the growth and anemia status of 0-2 years old infant and child in poor rural areas of Guangxi autonomous region. METHODS: 659 child under 2 years old were selected randomly to measure the length, weight and hemoglobin concentration, and to get the child basic condition information through questionnaire. RESULTS: In this area, the percent of 0-2 years old child growth retardation was 24.6%, under weight was 19.5%, wasting was 11.4% and anemia was 22.6%. CONCLUSION: The malnutrition and anemia status of 0-2 years old infant and child in investigated areas was severe. PMID- 20364593 TI - [Comparison of dietary vitamin A intake of residents in Jiangsu Province between 2002 and 2007]. AB - OBJECTIVE: To compare the change of dietary vitamin A intake between 2002 and 2007 in Jiangsu Province. METHODS: The data from the Nutrition Survey in Jiangsu province in 2002 and the fellow-up survey in 2007 were statistically analyzed with SAS 8.0. RESULTS: The average intake of retinol equivalent was 766.9 microg/d per reference man in 2007 (776.0 microg for man, 738.8 microg for women, 738.8 microg for urban and 776.0 microg for rural residents), which was higher than that in 2002. The percentage of retinol equivalent intake equal to or higher than RNI was 39.0% in 2007 and 16.1% in 2002. The dietary intake of vitamin A in northern Jiangsu was lower than that in southern Jiangsu and was positively correlated with the income. The dietary retinol equivalent from vegetable and fruits was increased, and from animal foods was decreased in 2007. CONCLUSION: The dietary vitamin A intake of residents in Jiangsu was improved in the past 5 years. The dietary vitamin A intake of low income population, women and residents in northern Jiangsu should be improved. PMID- 20364594 TI - [Survey on HIV/AIDS-related knowledge and behavior of high risk population in Taiyuan City]. AB - OBJECTIVE: To understand the status of HIV/AIDS-related knowledge and behavior of high risk population in Taiyuan City, and to explore the correlation between the two factors. METHODS: The questionnaires were designed according to the questionnaire for monitoring the behavior of HIV/AIDS-related high risk population in China, the basic knowledge, high-risk behavior and so on were included in the questionnaires. A random cluster sampling and stratified sampling method was used to interview with commercial sex workers, drug users and MSM (men who have sex with men) in Taiyuan City. EpiData 3.02 and SPSS 13.0 were used for data analysis. RESULTS: In the total of 531 respondents recruited in this study, 186 were commercial sex workers, 238 were drug users and 107 were MSM. The awareness of HIV/AIDS-related knowledge in sex workers was 61.9%, in drug users was 77.2% and in MSM was 90.4%. The condom user in sex workers at the last sexual activity was 74.9%, and in MSM was 58.9%. Sharing needle with others in intravenous drug users during the month before entering into the drug addiction treatment center was 57.9%. Except of sex workers in the top grade entertainment places, there was no statistically significant correlation between knowledge and behavior in these three high risk groups (r(s) = 0.789, P < 0.01). CONCLUSION: The awareness of HIV/AIDS-related knowledge and the frequency of using condom among these three high risk groups are relatively low. Health education as well as behavioral intervention should be emphasized. PMID- 20364595 TI - [Correlation analysis between fatigue and job stressors of nurses]. AB - OBJECTIVE: To explore the correlation between the degree of fatigue and job stressors in nurses. METHODS: A survey was conducted by using a questionnaire of, Fatigue Scale -14 (FS-14) and Nurse Job Stressors Scale in 306 nurses. RESULTS: The total score of fatigue was 7.17 +/- 3.41, the score of physical fatigue was 4.84 +/- 2.19, and the score of mental fatigue was 2.33 +/- 1.67 in nurses. The total score of fatigue, the score of physical fatigue and mental fatigue were positively correlated with five aspects of job stressors (P < 0.01). The total score of fatigue and the score of physical fatigue were positively correlated with age and the length of service. In logistic regression analysis, in comparison with ICU, the OR for total job stressors is 1.068, the OR for medicine department, surgical department, operation room, gynecology and pediatrics departments were 0.095, 0.187, 0.187, 0.029 and 0.005 respectively. CONCLUSION: Job stress is the major factor inducing fatigue in nurses, the managers of hospital should pay more attention to improve the capacity of nurses to cope with stress; and to care about their work and life to reduce the degree of fatigue. PMID- 20364596 TI - [Effects of ethylenethiourea on synthesis and secretion of thyroglobulin and iodide uptake of FRTL-5 cells]. AB - OBJECTIVE: To investigate the effects of ethylenethiourea (ETU) on thyroglobulin (TG) secretion and iodide uptake of FRTL-5 cells. METHODS: FRTL-5 cells were treated with 30, 150 and 270 microg/ml ETU, the cytotoxicity was tested by MTT and 3H-TdR, the synthesis and secretion of TG were analyzed by radioimmunoassay (RIA) and immunocytochemical method (ICC), the influence of ETU on tg and nis gene was determined by RT-PCR, and the iodide uptake of FRTL-5 cells was examined by isotopic tracer method. RESULTS: There is no significant cytotoxicity of ETU on FRTL-5 cells. The concentration of TG in the culture was decreased at 150 microg/ml and 270 microg/ml of ETU, and the concentration of TG and the transcription of tg gene in the cells were not obviously changed. The transcription of nis gene was markedly decreased at all dosages of ETU, but the iodide uptake of FRTL-5 cells was significantly decreased at 150 microg/ml and 270 microg/ml of ETU. CONCLUSION: The secretion of TG of FRTL-5 cells may be depressed by ETU, and the synthesis of TG could not be markedly changed. The transcription of nis gene could also be influenced by all dosages of ETU, but the iodide uptake of FRTL-5 cells was changed only at high levels of ETU. PMID- 20364597 TI - [Effects of perinatal exposure to sulphamethazine on the thyroid gland function of SD rats]. AB - OBJECTIVE: To study the effect of perinatal exposure sulphamethazine on the function of thyroid gland of SD rats. METHODS: Dams were given sulphamethazine 0, 50, 100 and 200 mg/(kg x d) respectively from gestational day (GD) 7 to postpartum day (P) 21. The sections of thyroid gland of pups 20 days after birth were stained by hematoxylin-eosin, and the expression of proliferating cell nuclear antigen (PCNA) were observed by immunohistochemistry staining. RESULTS: Compare with control, thyroid gland showed proliferation of follicular epithelium in each experimental group, and the numbers of PCNA positive cells in thyroid gland significantly higher than that of control (P < 0.05). CONCLUSION: Perinatal exposure to sulphamethazine may affect the function of thyroid gland of offspring. PMID- 20364598 TI - [Toxic effects of fluoride on rat cerebral cortex astrocytes in vitro]. AB - OBJECTIVE: To study astrocytes cellular cycle and the activities of SDH, 5'-NT and ACP in rat cerebral cortex astrocytes by NaF in vitro. METHODS: Astrocytes of rat cerebral cortex were purified and cultured in vitro to obtain the highly purified cells (identified by immunochemistry of anti-GFAP). The constituent ratio of cell cycle was analyzed by FCM after the cells were cultured with different levels of NaF for different time span. Activities of SDH, 5'-NT and ACP were tested by UV colorimetry. RESULTS: Cell cycle arrest transited from S phase to G2/M phase and subG1 cells increased in 1-5 mmol/L in the astrocyte cycle treated with different levels of NaF for different time span by using FCM. There was inverse correlation between the relative amount of the subG1 DNA and activities of SDH and ACP respectively (SDH: r = -0.84148, P < 0.05; ACP: r = 0.90416, P < 0.01) that were inhibited by NaF and 5 mmol/L NaF can inactivate 5' NT in astrocytes. CONCLUSION: NaF can induce cell cycle arrest from S to G2/M and inhibit activities of 5'-NT,SDH and ACP in astrocytes. PMID- 20364599 TI - [Determination of mercury by electric heat digestion and atomic fluorescence spectrometry]. AB - OBJECTIVE: To develop a method to determine mercury by electric heat digestion and atomic fluorescence spectrometry. METHODS: After electric heat digestion using aqua regia, the soil samples were determined by atomic fluorescence spectrometry. RESULTS: The linear range of the method was from 0 to 50 microg/L. The correlation coefficient was 0.9994. The detection limit of the method was 0.0051 microg/L. The relative standard deviations ranged from 1.55% to 6.52%. Four soil samples for quality control were determined by this method and all of the results were in the range of the true values. CONCLUSION: The optimized method have many advantages, such as high sensitivity, few interferences, wide linearity. At the same time,it is simple and rapid. PMID- 20364600 TI - [Effect of Arg-Gly-Asp peptide on the secretion of vascular endothelial growth factor from vascular endothelial cells]. AB - OBJECTIVE: To investigate the effect of Arg-Gly-Asp peptides (RGD peptides)on the secretion of vascular endothelial growth factor (VEGF) from vascular endothelial cells (VEC) and the mechanism. METHODS: Using VEC cultured from the arteries of human greater omentum as a model, and detecting the content of VEGF and the activity of protein kinase C (PKC) under different concentration of RGD. RESULTS: After incubation with 100-300 mg/ml of RGD peptide for 24h, the VEGF content and the activity of PKC in experimental group was significantly higher than that in control group (P < 0.01). CONCLUSION: The stimulation of RGD peptide to the secretion of VEGF from VEC is in a dose-dependent way, and the stimulation is regulated by activating PKC. PMID- 20364601 TI - [Simultaneous detection of Vibrio Cholerae O1 and O139 by real-time quantitative PCR]. AB - OBJECTIVE: Targeting the specific O-antigen gene cluster, a Taq-Man real-time fluorescence PCR assay was developed to detect 01 and O139 Vibrio cholera concurrently and avoid frequently occurred false positives. METHODS: Two pairs of specific primers and two Taq-Man fluorescent probes respectively targeting rfbM gene of Vibrio cholerae O1 and wbfR of 0139 were designed. After optimization of conditions, the specialty and sensitivity of the detection method were evaluated and ten simulated food samples and 128 clinical samples were tested. RESULTS: The detection limits of Vibrio cholerae O1 and O139 were 92 CFU/ml and 116 CFU/ml, which were almost the same with the usual PCR method. The developed real-time fluorescence PCR protocol detected only Vibrio cholerae O1 and O139 and it was not affected by many normal food pathogens such as Staphylococcus aureus and Salmonella, especially Vibrio cholerae O141 which contained TCP genes and Vibrio mimicus which contained ZOT gene. The clinical detect results of the developed assay and routine culture method were exactly the same. CONCLUSION: The developed detection assay could quantitatively detect Vibrio cholerae O1 and O139 concurrently in only 3 hours, and could avoid false positive, and thus was an efficacious method for detecting Vibrio cholerae O1 and O139 and could be used in a wide area such as entry-exit inspection and quarantine, food safety detection and clinical diagnose. PMID- 20364602 TI - [Effect of iron overload on experimental immunological liver injury in rats and the role of angiotensin]. AB - OBJECTIVE: To investigate the effect of iron overload on experimental immunological liver injury in rats and the roles of losartan (LOS), which is the selective antagonist of angiotensin II receptor subtype AT1. METHODS: Fifty male Wistar rats were divided by random into five groups (control, liver injury, liver injury + LOS, liver injury + ID and liver injury + ID + LOS). Immunological liver injury model was reproduceed by intravenous injection of BCG (Bacilli Calmette Guein) and then lipopolysaccharide (LPS). Iron overload model was created by intraperitoneal injection of iron dextran (ID). Serum iron (SI), transferrin (TRF), total protein (TP), the activity of asparatate aminotransferase (AST) and malondialdehyde (MDA) and liver iron (HIC) were tested. The expression of bcl-2 and Bax and the bax/bcl-2 ratio in hepatocyte were tested by flow cytometric analysis. Apoptotic index (AI) and proliferative index were also calculated. RESULTS: (1) In comparison with blank control group, the activity of serum AST was higher. Serum TP and TRF were lower in liver injury animals. Liver MDA increased significantly and along with a lower SOD activity. The expression of Bax in liver injury group was significantly higher than that in control group. The bax/ bcl-2 ratio and AI increased significantly in liver injury group. (2) Compared with liver injury group, the animals treated with ID showed an increase of serum AST activity, increased MDA and the expression of bax, the bax/bcl-2 ratio and AI. HIC was higher than the control group. (3) Compared with liver injury group, the activity of serum AST was lower and TRF was higher, MDA was reduced and SOD activity increased in animals treated with LOS. The expression of bcl-2 was increased, bax/bcl-2 ratio and AI decreased in this group. (4) In comparison with ID treated liver injury animals, the activity of AST and the content of MDA, and TRF increased in the animals treated with ID plus LOS. CONCLUSION: The immunological liver injury could be aggravated by iron overload through catalyzing lipid peroxidation and facilitating the apoptotic process of hepatocyte. Angiotensin faciliates in this kind of liver damage. PMID- 20364603 TI - [Determination of streptomycin in honey determined by hydrophilic interaction chromatography combined with tandem mass spectrometry]. AB - OBJECTIVE: To establish a method for the determination of streptomycin in honey by determined hydrophilic interaction chromatography combined with tandem mass spectrometry (HILIC-MS/MS). METHODS: A hilic column was used, and the mobile phase was consisted of acetonitrile (5 mmol/L ammonium acetate and 0.1% formic acid, 60:40). Samples were extracted by the cation-exchange SPE cartridge. The extraction samples were then identified and quantitated by HILIC-ESI-MS/MS. RESULTS: Linear calibration curves were obtained at the concentration ranges from 10. 5 microg/kg to 105 microg/kg (the correlation coefficients were above 0.99). The limit of detection was 1.05 microg/kg. The average recoveries for streptomycin spiked in honey ranged from 71.3 to 82.5% and their relative standard were between 3.4% and 8.2%. CONCLUSION: The method for determination of streptomycin in honey could be simple, sensitive and accurate. PMID- 20364604 TI - [Theanine, EGCG and caffeine determinated by HPLC]. AB - OBJECTIVE: A high-performance liquid chromatography (HPLC) method was developed for the determination of theanine in puer tea without derivatization and HPLC for EGCG and caffeine with ingredient elution system was put forward. METHODS: The theanine in the tea was extracted with water. The EGCG and caffeine was extracted with water: ethanol (3:7) by ultrasonic oscillation. After centrifugation, the extract was analyzed by HPLC-PDAD with a C18column and at the flow rate 1 ml/min. The theanine was determinated with 5 mmol/L SDS-acetonitrile mobile phase system (72:28), and both EGCG and caffeine with 0.05 mmol/L KH2PO4-methonal mobile phase system (80:20). RESULTS: The calibration of three ingredients was in good linearity. The recovery range is 85%-110%. The RSD is less than 10%. CONCLUSION: The method is accurate and stable. PMID- 20364605 TI - [Role of nutrition intervention in the treatment of hypertension]. AB - Hypertension is one of the most common cardiovascular diseases in the world. According to National data from 2002 Nutrition and Health Survey in China, the prevalence of hypertensions in adult was about 18.8% or it involved in about 180 million Chinese. Now hypertension has already become a major public health problem that could have severely impacted on population health status. This paper reviews the role of nutritional intervention in treating hypertension. PMID- 20364606 TI - [Development of a colloidal gold immuno-chromatography assay to detect methamphetamine]. AB - OBJECTIVE: A rapid detector method for non-professional staff detecting methamphetamine in scene, no instrument, sensitivity and specificity, would be set up. METHODS: Bagg albino C mice immunized with methamphetamine-modified bovine serum albumin were utilized for monoclonal antibody generation by the method of limited dilution technology. The detection of antibody typing kit was used for analysis the antibody subtype. Physical method was used for purified antibody labeled with colloidal gold. Colloidal gold test strip was composed and detected sensitivity and specificity. RESULTS: Seven special monoclonal antibodies were screened by limited dilution technology, among which valence of purified R6 antibody reached 10(8) via ciELISA, and belonged to IgG1 by the detection of antibody typing kit. Monoclonal antibody against methamphetamine labeling with colloidal gold particles was 5 microg/ml. The sensitivity of colloidal gold immuno-chromatography assay (GICA) for methamphetamine was 500 ng/ml. The cross-reactivity of the GICA detection card to eight analogs did not appear. CONCLUSION: GICA with high sensitivity, as a screening tool, may effectively contribute to Public Security Officers to detect narcotics in scene. PMID- 20364607 TI - [Review on the neuroprotective effects of green tea polyphenols for the treatment of neurodegenerative diseases]. AB - Considering the multi-etiological characters of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the diseases. Green tea polyphenols have been reported to possess more than two active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in neurodegeneration. This review aims to shed light on the multipharmacological neuroprotective activities and the mechanisms of green tea polyphenols on neurodegenerative diseases. PMID- 20364608 TI - Bronchoalveolar lavage: a forgotten tool! PMID- 20364609 TI - Validity of pneumonia severity index and CURB-65 severity scoring systems in community acquired pneumonia in an Indian setting. AB - BACKGROUND: Little information is available from India regarding prognostic factors in patients with community acquired pneumonia (CAP). METHODS: Hospital based prospective study to test the validity of pneumonia severity index (PSI) and the confusion, urea, respiratory rate, blood pressure, age over 65 years (CURB-65) risk scoring systems in patients with CAP (n=150). RESULTS: Although both CURB-65 class > or = III and PSI class > or = IV were 100% sensitive in predicting death, CURB-65 class > or = III had a higher specificity (74.6%) than PSI class > or = IV (52.2%) when used to predict death. In both PSI and CURB-65 risk scoring systems, mortality rate, need for intensive care unit (ICU) admission, prolonged need for intravenous (I.V.) antibiotics, prolonged duration of hospital stay and need for admission to ICU increased progressively with increasing scores. The PSI class > or = IV was more sensitive in predicting ICU admission than CURB-65. The duration of hospital stay was found to have a weak but significant correlation with PSI and CURB-65 criteria. Defervescence time also had a very weak but significant correlation with PSI and CURB-65 criteria. Duration of I.V. antibiotics had a moderately strong correlation with CURB-65 criteria but a weak correlation with PSI criteria. CONCLUSIONS: Both PSI and CURB 65 were found to have equal sensitivity to predict death from CAP. Specificity of CURB-65 was higher than that of PSI. However, PSI was more sensitive in predicting ICU admission than CURB-65. PMID- 20364610 TI - Breath carbon monoxide concentration in cigarette and bidi smokers in India. AB - OBJECTIVE: To measure and compare the breath carbon monoxide (CO) levels in cigarette and bidi smokers in India. METHODS: Breath CO was measured in 389 smokers (241 cigarette smokers,148 bidi smokers) using portable breath CO analyser (Bedfont-England, Smokelyzer). Tobacco contents and length of single stick of different brands of cigarette and bidi were also measured. RESULTS: Their mean age was 38.7 +/- 13.4 years. The average duration of smoking was 18.2 +/- 13.0 years. Average breath CO levels were 15.6 +/- 7.0 ppm in smokers and 4.07 +/- 1.16 ppm in non-smokers. Average breath CO level was significantly higher in bidi smokers (18.9 +/- 7.7 ppm) compared to cigarette smokers (13.6 +/- 5.8 ppm) when total consumption of cigarette/bidi was more than five pack-years (p = 0.002). Average tobacco weight of bidi (216.8 mg) was significantly less than cigarette (696 mg). CONCLUSIONS: Bidi is equally or more harmful than cigarette smoking. One bidi may be considered to one cigarette for calculating "pack-years" of smoking. PMID- 20364611 TI - Semi-rigid thoracoscopy: initial experience from a tertiary care hospital. AB - BACKGROUND: Thoracoscopy is usually carried out using rigid metallic instruments. Recently, video flex-rigid or semi-rigid thoracoscopes have been introduced. These have the advantage of easy maneuverability, although the biopsy samples are smaller as compared to those with rigid thoracoscopy. We have looked at the usefulness of flex rigid thoracoscope in the diagnosis and treatment of pleural diseases, remained undiagnosed after thoracentesis and closed biopsy. METHODS: Retrospective analysis of data of patients who underwent thoracoscopy for the evaluation of pleural disease. RESULTS: Thoracoscopy was done in 21 patients using a flex-rigid thoracoscope in our institution. The indication was pleural effusion with inconclusive or negative pleural fluid cytology and blind pleural biopsy in 18 of the 21 patients. Thoracoscopic biopsy was positive in 12 of the 18 patients (66.7%). Of the six who had a negative biopsy, the procedure indirectly helped in patient management in five. There were no significant procedure-related complications. CONCLUSION: Thoracoscopy with flex-rigid thoracoscope is a useful diagnostic tool in the evaluation of pleural effusions with negative blind pleural biopsy and cytology. PMID- 20364612 TI - Pulmonary hypertension associated with chronic obstructive pulmonary disease. AB - Pulmonary hypertension (PH) is likely to complicate chronic obstructive pulmonary disease (COPD) in a large proportion of patients, especially those with severe disease. Majority of patients have a mild to moderate elevation in the pulmonary artery pressure that usually does not require specific treatment. A small subset of patients, however, develops severe PH that is "out-of-proportion" to the severity of COPD. Generally considered a consequence of chronic hypoxaemia, endothelial dysfunction has now been recognised to play an important role in the pathogenesis of PH in COPD. Pulmonary vessels remodelling characterised by intimal enlargement with proliferating smooth muscle cells, medial hypertrophy, arteriolar muscularisation and endothelial cell proliferation, especially affecting the small arterioles and arteries, leads to permanent changes in the vascular structure and function. Clinical recognition of PH is difficult. Echocardiography is used for screening while right heart catheterisation is the gold standard for diagnosis. In patients who have a moderate degree of chronic hypoxaemia, long term oxygen therapy is indicated and is the only therapeutic measure so far known to retard the progress of PH. Newer therapies targeting the specific abnormalities of vasoconstrictor-vasodilator balance, arising as a consequence of endothelial dysfunction, are under investigation and may offer a management option especially in severe PH associated with COPD. PMID- 20364613 TI - Diffuse panbronchiolitis associated with malignant thymoma. PMID- 20364614 TI - Diffuse panbronchiolitis: report of a rare disease from India. AB - Initially described by a group of Japanese clinicians and pulmonary pathologists to distinguish it from other chronic obstructive lung diseases, diffuse panbronchiolitis (DPB) is an uncommon disorder which has been reported largely from the eastern world. It is imperative to recognise this condition because of its potentially treatable nature. Recently, long-term macrolide therapy has revolutionised its management. Herein, we describe a 65-year-old male who was being managed as a case of chronic bronchitis before this diagnosis was suspected and proved. PMID- 20364615 TI - Multiple myeloma presenting with multiple thoracic manifestations. AB - Multiple myeloma is a malignant proliferation of plasma cells that affects mainly bone marrow but may also involve other organs as well. We report thoracic involvement in the form of left-sided pleural effusion, osseous lesions, bronchial infiltration, and mediastinal lymphadenopathy in a 61-year-old woman, non-smoker presented with chest pain, dyspnoea, cough and deterioration in general health over the preceding seven months. Immunoelectrophoresis and immunofixation showed raised kappa-light chain immunoglobulin G (IgG) in serum and pleural fluid. Bronchial and pleural biopsies documented myelomatous infiltration and bone marrow aspirate revealed extensive plasma cell infiltration. At eight months, following the fourth cycle of melphalan, endoxan and prednisone based chemotherapy, the patient died. PMID- 20364616 TI - Yellow nail syndrome and adnexal tumour: causal or casual association? AB - The yellow nail syndrome is an uncommon condition characterised by dystrophic nails, pulmonary disturbances and lymph oedema. In Brazil as well as in India, this syndrome has been scarcely described, at least in part due to diagnosis pitfalls related with darker skin pigmentation. A case of adnexal malignancy developing several decades after initial signs of yellow nail syndrome is reported in a 61-year-old Brazilian female admitted for evaluation of peripheral oedema. She reported recurrent sinusitis and bronchitis, and three antecedent pneumonias. Physical examination showed yellow thickened nails and lower limb oedema, and a painless huge adnexal mass. Diverse tumours have been described associated with yellow nail syndrome; however, associations can also occur by chance. The present report attempts to raise the awareness about casual co existence of malignancy and the syndrome. PMID- 20364617 TI - Endotracheal tuberculous stenosis: ventilation rescue and bronchography guided stenting. AB - We present the case of a 16-year-old female patient who presented with dyspnoea, cough and noisy breathing that progressed further in hospital with the development of stridor and severe respiratory compromise requiring mechanical ventilatory support. Investigations were consistent with a diagnosis of endotracheal tuberculosis with tracheal and bronchial stenosis. Despite adequate anti-tuberculous therapy and ventilation the patient had high airway pressures, low tidal volumes and hypercapnia, which prevented weaning from mechanical ventilation. Balloon dilatation and stenting of the 4.5cm long, 2.3mm diameter stenotic tracheal segment was performed under radiological guidance. The patient was weaned successfully from the ventilator post-procedure. This report illustrates the successful management of an uncommon presentation of a common disease with modern endoscopic therapy. PMID- 20364618 TI - Cannon ball lucencies from last century: lucite balls used to treat pulmonary tuberculosis. PMID- 20364619 TI - How to plan for methane mitigation and utilisation strategies? PMID- 20364620 TI - What's going on with young people today? the long and twisting path to adulthood. AB - Richard Settersten and Barbara Ray examine the lengthening transition to adulthood over the past several decades, as well as the challenges the new schedule poses for young people, families, and society. The authors begin with a brief history of becoming an adult, noting that the schedule that youth follow to arrive at adulthood changes to meet the social realities of each era. For youth to leave home at an early age during the 1950s, for example, was "normal" because opportunities for work were plentiful and social expectations of the time reinforced the need to do so. But the prosperity that made it possible for young adults of that era to move quickly into adult roles did not last. The economic and employment uncertainties that arose during the 1970s complicated enormously the decisions that young adults had to make about living arrangements, educational investments, and family formation. The authors next take a closer look at changes in the core timing shifts in the new transition-the lengthening time it now takes youth to leave home, complete school, enter the workforce, marry, and have children. They stress that today's new schedule for attaining independence leaves many families overburdened as they support their children for an extended period. The continued need to rely on families for financial assistance, the authors say, exacerbates the plight of young people from a variety of vulnerable backgrounds. It also raises complex questions about who is responsible for the welfare of young people and whether the risks and costs newly associated with the early adult years should be absorbed by markets, by families, or by governments. Settersten and Ray stress that the longer transition to adulthood strains not only families but also the institutions that have traditionally supported young Americans in making that transition-such as residential colleges and universities, community colleges, military service, and national service programs. They emphasize the need to strengthen existing social institutions and create new ones to reflect more accurately the realities of a longer and more complex passage into adult life. PMID- 20364621 TI - Immigration and adult transitions. AB - Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Ruben Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage counterparts, including blacks and whites. The authors document the demographic changes in the United States over the past forty years and describe the ways in which generation and national origin shape the experiences of these newcomers as they become adults. Rumbaut and Komaie point out that immigrant groups experience gaps in social, economic, and legal status that are even greater than the gaps between native whites and blacks. By far the most-educated (Indians) and the least-educated (Mexicans) groups in the United States today are first-generation immigrants, as are the groups with the lowest poverty rate (Filipinos) and the highest poverty rate (Dominicans). These social and economic divides reflect three very different ways immigrants enter the country: through regular immigration channels, without legal authorization, or as state-sponsored refugees. For many ethnic groups, significant progress takes place from the first to the second generation. But, say the authors, for millions of young immigrants, a lack of legal permanent residency status blocks their prospects for social mobility. Having an undocumented status has become all the more consequential with the failure of Congress to pass comprehensive federal immigration reforms. In the coming two decades, as the U.S. native-parentage labor force continues to shrink, immigrants and their children are expected to account for most of the growth of the nation's labor force, with the fastest growing occupations requiring college degrees. Rumbaut and Komaie stress that one key to the nation's future will be how it incorporates young adults of immigrant origin in its economy, polity, and society, especially how it enables these young adults to have access to, and to attain, postsecondary education and its manifold pyoffs. PMID- 20364622 TI - On a new schedule: transitions to adulthood and family change. AB - Frank Furstenberg examines how the newly extended timetable for entering adulthood is affecting, and being affected by, the institution of the Western, particularly the American, family. He reviews a growing body of research on the family life of young adults and their parents and draws out important policy implications of the new schedule for the passage to adulthood. Today, says Furstenberg, home-leaving, marriage, and the onset of childbearing take place much later in the life span than they did during the period after World War II. After the disappearance of America's well-paying unskilled and semi-skilled manufacturing jobs during the 1960s, youth from all economic strata began remaining in school longer and marrying and starting their own families later. Increasing numbers of lower-income women did not marry at all but chose, instead, non-marital parenthood-often turning to their natal families for economic and social support, rather than to their partners. As the period of young adults' dependence on their families grew longer, the financial and emotional burden of parenthood grew heavier. Today, regardless of their income level, U.S. parents provide roughly the same proportion of their earnings to support their young adult children. Unlike many nations in Europe, the United States, with its relatively underdeveloped welfare system, does not invest heavily in education, health care, and job benefits for young adults. It relies, instead, on families' investments in their own adult children. But as the transition to adulthood becomes more protracted, the increasing family burden may prove costly to society as a whole. Young adults themselves may begin to regard childbearing as more onerous and less rewarding. The need to provide greater support for children for longer periods may discourage couples from having additional children or having children at all. Such decisions could lead to lower total fertility, ultimately reduce the workforce, and furthdr aggravate the problem of providing both for increasing numbers of the elderly and for the young. U.S. policy makers must realize the importance of reinforcing the family nest and helping reduce the large and competing demands that are being placed on today's parents. PMID- 20364623 TI - Programs and policies to assist high school dropouts in the transition to adulthood. AB - Dan Bloom of MDRC examines policies and programs designed to help high school dropouts improve their educational attainment and labor market outcomes. So called "second-chance" programs, he says, have long provided some combination of education, training, employment, counseling, and social services. But the research record on their effectiveness is fairly thin, he says, and the results are mixed. Bloom describes eleven employment- or education-focused programs serving high school dropouts that have been rigorously evaluated over the past thirty years. Some relied heavily on paid work experience, while others focused more on job training or education. Some programs, especially those that offered paid work opportunities, generated significant increases in employment or earnings in the short term, but none of the studies that followed participants for more than a couple of years found lasting improvements in economic outcomes. Nevertheless, the findings provide an important foundation on which to build. Because of the high individual and social costs of ignoring high school dropouts, the argument for investing more public funds in services, systems, and research for these young people is strong. The paucity of conclusive evidence, however, makes it hard to know how to direct resources and magnifies the importance of ensuring that all new initiatives provide for rigorous evaluation of their impacts. Bloom concludes with recommendations for policy and research aimed at building on current efforts to expand and improve effective programs for dropouts while simultaneously developing and testing new approaches that might be more effective and strengthening local systems to support vulnerable young people. He stresses the importance of identifying and disseminating strategies to engage young people who are more seriously disconnected and unlikely to join programs. A recurring theme is that providing young people with opportunities for paid work may be useful both as an engagement tool and as a strategy for improving long term labor market outcomes. PMID- 20364624 TI - Young adults and higher education: barriers and breakthroughs to success. AB - Although access to higher education has increased substantially over the past forty years, student success in college--as measured by persistence and degree attainment--has not improved at all. Thomas Brock reviews systematic research findings on the effectiveness of various interventions designed to help at-risk students remain in college. Brock shows how changes in federal policy and public attitudes since the mid-1960s have opened up higher education to women, minorities, and nontraditional students and also shifted the "center of gravity" in higher education away from traditional four-year colleges toward nonselective community colleges. Students at two-year colleges, however, are far less likely than those at four-year institutions to complete a degree. Brock argues that the nation's higher education system must do much more to promote student success. Three areas, he says, are particularly ripe for reform: remedial education, student support services, and financial aid. In each of these three areas, Brock reviews programs and interventions that community colleges have undertaken in order to raise completion rates. Some colleges have, for example, experimented with remedial programs that build social cohesion between students and faculty and integrate content across courses. Other colleges have tested student support service programs that offer counseling and advising that are regular, intensive, and personalized. Still others have experimented with ways to simplify the financial aid application process and incentivize students to earn good grades and persist in school. Research shows that such programs and interventions can improve student outcomes, but Brock argues that more must be done to bring proven practices to scale and to test new ideas that might lead to better results. Institutions that most need help'are those that provide the greatest access to nontraditional and underprepared students in community colleges and less selective universities. PMID- 20364625 TI - Labor market outcomes and the transition to adulthood. AB - According to Sheldon Danziger and David Ratner, changes in the labor market over the past thirty-five years, such as labor-saving technological changes, increased globalization, declining unionization, and the failure of the minimum wage to keep up with inflation, have made it more difficult for young adults to attain the economic stability and self-sufficiency that are important markers of the transition to adulthood. Young men with no more than a high school degree have difficulty earning enough to support a family. Even though young women have achieved gains in earnings, employment, and schooling relative to men in recent decades, those without a college degree also struggle to achieve economic stability and self-sufficiency. The authors begin by describing trends in labor market outcomes for young adults-median annual earnings, the extent of low-wage work, employment rates, job instability, and the returns to education. Then they examine how these outcomes may contribute to delays in other markers of the transition to adulthood-completing an education, establishing independent living arrangements, and marrying and having children. They conclude that adverse changes in labor market outcomes are related to those delays but have not been shown to be the primary cause. Danziger and Ratner next consider several public policy reforms that might improve the economic outlook for young adults. They recommend policies that would increase the returns to work, especially for less educated workers. They propose raising the federal minimum wage and adjusting it annually to maintain its value relative to the median wage. Expanding the Earned Income Tax Credit for childless low-wage workers, the authors say, could also raise the take-home pay of many young adult workers, with minimal adverse employment effects. New policies should also provide work opportunities for young adults who cannot find steady employment either because of poor economic conditions or because of physical and mental disabilities or criminal records that make it hard for them to work steadily even when the economy is strong. Finally, the authors recommend increasing federal Pell grants for college and improving access to credit for would-be college students to raise the educational attainment of young adults from low-income families. PMID- 20364626 TI - Civic engagement and the transition to adulthood. AB - Constance Flanagan and Peter Levine survey research on civic engagement among U.S. adolescents and young adults. Civic engagement, they say, is important both for the functioning of democracies and for the growth and maturation it encourages in young adults, but opportunities for civic engagement are not evenly distributed by social class or race and ethnicity. Today's young adults, note the authors, are less likely than those in earlier generations to exhibit many important characteristics of citizenship, raising the question of whether these differences represent a decline or simply a delay in traditional adult patterns of civic engagement. Flanagan and Levine also briefly discuss the civic and political lives of immigrant youth in the United States, noting that because these youth make up a significant share of the current generation of young adults, their civic engagement is an important barometer of the future of democracy. The authors next survey differences in civic participation for youth from different social, racial, and ethnic backgrounds. They explore two sets of factors that contribute to a lower rate of civic engagement among low-income and minority young adults. The first is cumulative disadvantage-unequal opportunities and influences before adulthood, especially parental education. The second is different institutional opportunities for civic engagement among college and non college youth during the young-adult years. Flanagan and Levine survey various settings where young adults spend time-schools and colleges, community organizations, faith-based institutions, community organizing and activism projects, and military and other voluntary service programs-and examine the opportunities for civic engagement that each affords. As the transition to adulthood has lengthened, say the authors, colleges have become perhaps the central institution for civic incorporation of younger generations. But no comparable institution exists for young adults who do not attend college. Opportunities for sustained civic engagement by year-long programs such as City Year could provide an alternative opportunity for civic engagement for young adults from disadvantaged families, allowing them to stay connected to mainstream opportunities and to adults who could mentor and guide their way. PMID- 20364627 TI - The military and the transition to adulthood. AB - Ryan Kelty, Meredith Kleykamp, and David Segal examine the effect of military service on the transition to adulthood. They highlight changes since World War II in the role of the military in the lives of young adults, focusing especially on how the move from a conscription to an all-volunteer military has changed the way military service affects youths' approach to adult responsibilities. The authors note that today's all-volunteer military is both career-oriented and family oriented, and they show how the material and social support the military provides to young servicemen and women promotes responsible membership in family relationships and the wider community. As a result, they argue, the transition to adulthood, including economic independence from parents, is more stable and orderly for military personnel than for their civilian peers. At the same time, they stress that serving in the military in a time of war holds dangers for young adults. The authors examine four broad areas of military service, focusing in each on how men and women in uniform today make the transition to adulthood. They begin by looking at the social characteristics of those who serve, especially at differences in access to the military and its benefits by socio-demographic characteristics, such as age, gender, race and ethnicity, social class, and sexual orientation. Military service also has important effects on family formation, including the timing of marriage and parenthood, family structure, and the influence of military culture on families. Family formation among servicemen and women, the authors observe, is earlier and more stable than among civilians of the same age. The authors then consider the educational and employment consequences of service. Finally, they scrutinize the dangers of military service during times of war and examine the physical and psychological effects of wartime military service. They also note the sexual trauma endured both by male and female military personnel and the physical and symbolic violence women can experience in a male-dominated institution. Kelty, Kleykamp, and Segal conclude by seeking policy lessons from the military's success in facilitating the transition to adulthood for young men and women in uniform. PMID- 20364628 TI - Vulnerable populations and the transition to adulthood. AB - D. Wayne Osgood, E. Michael Foster, and Mark E. Courtney examine the transition to adulthood for youth involved in social service and justice systems during childhood and adolescence. They survey the challenges faced by youth in the mental health system, the foster care system, the juvenile justice system, the criminal justice system, and special education, and by youth with physical disabilities and chronic illness, as well as runaway and homeless youth. One problem is that the services these vulnerable populations receive from these systems as children and adolescents often end abruptly as they transition to adulthood, even though the need for them continues. Youth must leave systems tailored for clients their age and, if they are eligible for further services at all, enter adult systems that are not equipped to address their needs. One exception is the special education system, whose services extend into early adulthood and are designed for individuals' needs. The authors review current public policies directed toward vulnerable youth in transition and find problems in four areas: eligibility criteria that exclude youth from services that might benefit them, inadequate funding for transition services, a lack of coordination across service systems, and inadequate training about young-adult developmental issues for service professionals. The authors then discuss policy options that can help create a developmentally appropriate and socially inclusive system of support for vulnerable youth. Among the options are strengthening all programs for youth in transition, improving the existing systems of care for children and adolescents, addressing the loss of access to services at the age of majority, and coordinating today's multiple systems into a single coherent system. The authors see heightened governmental interest in better supports for vulnerable young adults, both through expanding the federal role in their lives and through improving coordination of the systems that serve them. The Fostering Connections Act of 2008, for example, extended services to adolescents in foster care from the age of eighteen to the age of twenty-one. PMID- 20364629 TI - A clearer route to carbon footprinting. AB - Independent sustainability consultant and BREEAM healthcare assessor James Rainbird explains in detail how he recently helped a large primary care Trust in north-west England with its carbon footprinting. Arguing that PCTs face particular problems in collecting data, he believes there is a need for concise practical pointers to help Trusts complete such an exercise, a number of which he presents in this article. PMID- 20364630 TI - Evidence-based design 'evolving fast'. PMID- 20364631 TI - Fighting the waterborne menace. AB - Although only around 400 cases are reported annually to the U.K.'s Health Protection Agency (HPA), climate change, and thus warmer cold water supplies entering hospitals, the bacterium's apparent ability to mutate, and the considerable challenge of properly monitoring, and successfully identifying and addressing, all potential infection sources on a large hospital estate mean an increasing risk of hospital patients acquiring the potentially deadly waterborne infection, Legionnaires' disease. This was the warning from a top U.K. microbiologist at a recent "waterborne infection masterclass" organised by specialist water filtration product supplier Pall Medical in Antwerp. Jonathan Baillie reports. PMID- 20364632 TI - High-rise healing for young cancer patients. AB - A "teenage penthouse" designed in consultation with patients and nurses with an "inspiring, homely feel", and conceived using "sensitive architecture" to support young people in their fight against cancer, is how architect John McRae of ORMS Architecture Design describes the award-winning new Teenage Cancer Trust (TCT) unit at the University Hospital of Wales in Cardiff. Jonathan Baillie reports. PMID- 20364633 TI - Environment critical to teenagers' recovery. AB - The Teenage Cancer Trust (TCT), the charity devoted to improving the lives of teenager cancer sufferers, has released the initial results of an independent study which it says prove that a high quality built environment, of the calibre seen in its 13 existing U.K. teenage cancer units, not only boosts patient morale by giving sick youngsters a feeling of control, but also encourages young cancer sufferers to complete their treatment, significantly impacting the number of positive outcomes. Jonathan Baillie reports on the study's London launch. PMID- 20364634 TI - Why it pays to 'grill' your supplier. AB - When it comes to ensuring that your cold storage operation and maintenance meets MHRA requirements, it pays to ensure that your service supplier knows what it is doing. So says Joe Fudge, instrumentation service manager for ABB's instrumentation business in the U.K., who outlines some of the key factors to consider when selecting a supplier of cold chain mapping services. PMID- 20364635 TI - Purity issues require a cool head. AB - According to water purification equipment suppliers, estates and facilities teams are now increasingly involved in specifying, purchasing, configuring, and maintaining the sophisticated equipment required to clean and disinfect endoscopes, and, more especially, the water purification equipment needed to ensure an effective "clean". However, changing guidelines on the levels of water purity required for thorough "reprocessing", varying standards of incoming mains water, and differing opinions on which sanitisation methods best combat bacteria, make it vital that they fully understand the issues before specifying potentially costly purification equipment which may otherwise not perform quite as expected. PMID- 20364636 TI - A common sense approach to sprinklers. AB - As debate continues over the importance of incorporating automatic sprinkler systems into healthcare facilities, Andy Passingham, associate director at Arup Fire, considers how Arup, the multi-disciplinary engineers for two high profile new Welsh hospitals under construction in Ebbw Vale and Caerphilly, addressed fire safety on both projects. He highlights how the installation of sprinklers should not only improve fire safety, but has also contributed to a number of wider design elements which should enhance the patient, staff, and visitor experience. PMID- 20364637 TI - Simulated 'hospital' gives real insight. AB - A simulated hospital environment has been created at Trumpf's new facilities in Luton with the aim of promoting a better understanding of environmental factors in improving patient recovery, as well as key considerations such as lighting and televised training in theatres. Louise Frampton reports. PMID- 20364638 TI - Temperatures kept cool in Southampton. AB - According to Digitron, hospitals countrywide are seeing the benefits of DigiTrak, the company's automatic wireless temperature monitoring system. Katey McDonald, the company's marketing manager, outlines how the system replaces traditional methods of data collection by providing a single networked package, and describes its use at Southampton General Hospital for blood monitoring, with the help of advanced biomedical scientist and quality officer there Marie Cundall. PMID- 20364639 TI - Diversity in healthcare: leading toward culturally competent care. PMID- 20364640 TI - Diversity in healthcare: time to get REAL! AB - Cross-cultural healthcare involves three key issues: racial and ethnic disparities in the quality of healthcare provided to minority patients; cross cultural value differences between immigrant patients and Western medical providers; and providing language access and assistance to limited English proficient (LEP) and disabled persons. Addressing these key issues represents a compelling diversity agenda for a new generation of healthcare executives. This article describes each of these challenges and the cutting-edge strategies that leading healthcare organizations are using to address them. PMID- 20364641 TI - Addressing diversity and moving toward equity in hospital care. AB - Healthcare disparities are a major challenge for hospital and healthcare system leadership. Leaders must possess vision, visibility, and ability to drive organizational change toward an environment that fosters diversity and cultural competence. As challenging economic conditions force management to make difficult budgetary decisions, the integration of equity into the organization's core mission and strategic process is essential for sustainability. Building organizational capacity requires systematic actions including workforce composition, training and development, and policy advocacy. This article offers perspectives on the current state of diversity in hospitals, exemplars from pediatric hospitals, and considerations for the future. Healthcare leaders are influential in shaping the future of the organization through strategic planning and resource allocation to those efforts that enhance services, programs, and processes that support a culture of diversity and equity. PMID- 20364642 TI - Disaggregating diversity data for optimal decision making. PMID- 20364643 TI - Diversity in healthcare: driven by leadership. PMID- 20364644 TI - Our experience: strong foundations accelerate change in diversity and cultural competence. PMID- 20364645 TI - Reducing the patient fall rate in a rural health system. AB - In healthcare facilities, patient falls have been a major contributing factor associated with patient injuries that result in increased costs and increased length of stay. Recent actions by the Department of Health and Human Services, enacted through the Department of Medicare and Medicaid Services, now hold healthcare facilities financially responsible for injury to patients that result from falls (CMS Hospital Acquired Conditions). Because of these rulings, costs associated with patient falls are now a greater threat to the survival of rural healthcare facilities. The rate of patient falls at Wise Regional Health System was unacceptably high. As a result of statistically analyzing the demographics of previous fall victims, and initiating additional interventions for identified patients, Wise Regional Health System has been successful in drastically decreasing their inpatient fall rate. PMID- 20364646 TI - Hospital patient safety levels among healthcare's "most wired" institutions. AB - Our study compared adverse patient safety events among hospitals that have received the distinction "Most Wired" as rated by the Hospital and Health Network publication versus comparison hospitals. Risk-adjusted Patient Safety Indicators (PSIs) were calculated for 558 general adult medical/surgical hospitals participating in the Agency for Healthcare Quality and Research's Nationwide Inpatient Sample. When compared using mean risk-adjusted PSI rates, no significant differences in performance for specific PSIs were observed between hospitals affiliated with the "Most Wired" label and those without the designation using objective measures of safety. PMID- 20364647 TI - Interview with a quality leader: Dale W. Bratzler, DO, MPH on performance measures. Interview by Jason Trevor Fogg. AB - Dale Bratzler, DO, MPH, currently serves as the President and CEO of the Oklahoma Foundation for Medical Quality (OFMQ). In addition, he provides support as the Medical Director of the Patient Safety Quality Improvement Organization Support Center at OFMQ. In these roles, he provides clinical and technical support for local and national hospital quality improvement initiatives. He is a Past President of the American Health Quality Association and a recent member of the National Advisory Council for the Agency for Healthcare Research and Quality. Dr. Bratzler has published extensively and frequently presents locally and nationally on topics related to healthcare quality, particularly associated with improving care for pneumonia, increasing vaccination rates, and reducing surgical complications. He received his Doctor of Osteopathic Medicine degree at the Kansas City University of Medicine and Biosciences, and his Master of Public Health degree from the University of Oklahoma Health Sciences Center College of Public Health. Dr. Bratzler is board certified in internal medicine. PMID- 20364648 TI - Interdisciplinary process improvement for enhancing blood transfusion safety. AB - We describe a multipronged, multidisciplinary effort to improve the safety of blood transfusion in our hospital. System-wide practices related to the ordering, delivery, and transfusion of blood products were addressed including: (1) appropriate selection of patients and utilization of blood, (2) accurate blood product labeling and tracking, (3) reliable transportation of blood products between the transfusion service laboratory and the bedside, (4) electronic verification of patients and products at the point of transfusion, and (5) documentation of transfusion events in the patient's medical record. By implementing new technologies and focusing LEAN process improvement techniques on the preanalytical, analytical, and postanalytical phases of the transfusion cycle, we have been able to significantly reduce the risk of transfusion error in our patient population. PMID- 20364649 TI - Establish the habit: influenza vaccination for health care personnel. AB - Influenza vaccination of health care personnel (HCP) is a patient safety issue, but the national rate is only 42%. Following an intervention in 2006-2007, HCP in a large health system were surveyed. Self-reported influenza vaccination rate was 61.6% overall, did not differ by race, education level, or employment status but was higher for older HCP (> or =50 years; p=.002). In logistic regression, the strongest predictor of vaccination was receiving influenza vaccine the previous year, although other factors were significantly associated for younger and older HCP groups. Establishing the influenza vaccination habit using age-based targeted messages may be the most effective way to increase rates for HCP without mandates. PMID- 20364651 TI - [Developmental unrealistic expectations]. PMID- 20364650 TI - Improving the quality of diabetes care: a behavioral health intervention. AB - The purpose of this study is to assess the impact of a group-based program on glucose control for adults with diabetes. Ninety-two adults completed the program aimed at identifying and overcoming barriers to diabetes self-management with the use of behavioral strategies. A comparison group consisted of 275 adults with diabetes not participating in the program matched for age, gender, type of insurance coverage, and initial hemoglobin Alc (HbAlc) result. Members completing the program demonstrated significant improvements in HbAlc results at both the first and second postgroup measurements. Regression analyses identified initial HbAlc result and the interaction of condition and initial HbAlc as significant predictors of improvement in HbAlc. The quality of diabetes care and treatment outcomes can be enhanced with the inclusion of a low-cost, structured program led by a behavioral health professional. PMID- 20364652 TI - [Pacifier, Nuggi, thumbsucking: when should a child stop?]. PMID- 20364653 TI - [Possibilities and limits of social pediatrics in Germany]. PMID- 20364654 TI - [Request meets offer: supporting routine parenting competence]. PMID- 20364655 TI - [Significance of physical activity for child development]. PMID- 20364656 TI - [Inpatient and ambulatory pediatric health and sickness nursing: hand in hand]. PMID- 20364657 TI - [The best day care for my child. What you should consider when you enroll your child in nursery care, kindergarten or child day care center]. PMID- 20364658 TI - [Caution, nutrition rumors. Eat, my child--spinach has a lot of iron!]. PMID- 20364659 TI - [World Health Day and its questionable role]. PMID- 20364660 TI - [Healing with cryotherapy: whole body cryotherapy at -110 degrees C!]. PMID- 20364661 TI - [Are children and adolescents of today more sedentary?]. PMID- 20364662 TI - [Genetic diagnosis regulation in force]. PMID- 20364663 TI - [MRSA contamination of computer keyboards: an indirect marker of hand hygiene?]. PMID- 20364664 TI - [Pathogenicity of West Nile virus: molecular markers]. AB - The review describes the phenotypic properties, structure, and expression pattern of West Nile virus genome (Flaviviridae, Flavivirus, Japanese encephalitis antigenic complex), as well as the clinical picture and pathogenesis of its etiologically related disease West Nile fever. It also analyzes the available data on the impact of genetic mutations in the genome on the biological properties of the virus. PMID- 20364665 TI - [The maturation steps of human immunodeficiency virus and the role of proteolysis]. AB - HIV-1 virions are as immature noninfectious particles lacking a central core. Shortly after budding, virions temporally mature and acquire cores and infectious activity. The cause of maturation remains poorly studied. We have revealed that the virions produced early after infection following 24-36 hours, never mature and remain noninfectious, and only virions produced 48-72 hours after infection mature. The mature virions contain 3 times more genomic viral RNA than "early" virus. The "early" virions contain the same proteolytically cleaved Gag proteins as mature virions in contrast to the accepted version. The virus protease inhibitor Indinavir sulfate (IS) fully blocks infectivity when added early after infection. The early proteolysis of Gag precursor in the infected cells and inclusion into the virions of cellularly cleaved matrix protein (cMA) are shown in the IS-treated cells. cMA is associated with genomic viral RNA. PMID- 20364666 TI - [Analysis of HIV-1 integrase gene polymorphism in an HIV-infected population from the nosocomial outbreak of HIV infection in the south of Russia in 1989]. AB - The paper presents the data of an investigation of the polymorphism of the pol gene encoding HIV-1 integrase in a HIV subtype G infected population formed during the 1989 HIV-infection outbreak. The investigators analyzed 41 samples of the viruses obtained in 2005-2007. Polymorphism at codons associated with integrase resistance to chemicals was observed in 11 virus variants. The circulation of mutation viruses that potentially promote the formation of resistance to the integrase inhibitors raltegravir and elvitegravir has been established in untreated patients. PMID- 20364667 TI - [GBV-C infection in HIV-infected patients in the Russian Federation]. AB - The spread and genotypical variability of GBV-C virus were determined among the HIV-positive patients in the Russian Federation. More than a fourth (26.2%) of the HIV-infected patients were shown to have GBV-C coinfection; all virus isolates belonged to genotype 2 with a predominance of subtype 2a. Analysis of the impact of GBV-C coinfection on HIV burden and CD4 lymphocyte levels showed no significant impact on these basic characteristics of HIV infection. However, coinfection with GBV-C and HIV was associated with the higher frequency of undetectably low ( < 400 copies/ml) of HIV burden, which enables GBV-C infection to be regarded as a potentially favorable factor in HIV infection. PMID- 20364668 TI - [Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more frequently encountered in idiopathic infertility and correlates with the reduction in sperm parameters]. AB - The present investigation was undertaken to study the detection rate of herpes simplex virus (HSV) and cytomegalovirus (CMV) in the ejaculates of males with infertility and to evaluate the impact of virus infection on the major parameters of sperm. Ejaculates from 808 patients were studied. As compared with apparently healthy individuals, the coupled males with primary infertility were found to have HSV more frequently in both the whole ejaculate (31% versus 17%; p = 0.049) and the fraction of actively motile spermatozoa (30% versus 8%; p = 0.016). Ejaculate HSV detection directly correlated with the reduced amount of actively motile spermatozoa (p = 0.0001) and the smaller proportion of morphologically normal forms of germ cells (p = 0.002). CMV was found to have no impact on the motility and morphology of spermatozoids in the ejaculate. Both HSV and CMV in the male ejaculate were significantly more frequently detectable in winter months. The findings lead to the conclusion that HSV is one of the factors for male infertility and can negatively affect the results of assisted reproductive technologies. PMID- 20364669 TI - [Comparative study of resistance to acycloguanosine and acycloguanosine H phosphonate in herpes simplex virus]. AB - The ability of acycloguanosine H-phosphate to inhibit the reproduction of herpes simplex virus type 1 (HSV-1) variants, including its acycloguanosine (acyclovir) resistant ones, was studied. Acycloguanosine H-phosphate-resistant HSV-1 variants were obtained. It was found that these variants were cross-resistant to thymidine kinase-dependent HSV reproduction inhibitors, but preserved sensitivity to Apa-A and phosphonoacetic acid. PMID- 20364670 TI - [Inactivated herpes simplex virus types 1 and 2 divaccine as an agent for effective immunoprophylaxis of recurrent genital herpes]. AB - Prevention of recurrent genital herpes with the inactivated herpetic divaccine Vitaherpavac against herpes simplex virus types 1 and 2 has a number of advantages over the most commonly used symptomatic therapy: it ceases or significantly reduces the number of recurrences and accordingly prolongs a relapse-free interval, abolishes viremia and the manifestations of clinical symptoms of recurrences, induces no dependence to the vaccine. Coadministration of the Vitaherpavac vaccine and the immunomodulator Giaferon has been shown to have some advantage over vaccination only. The new formulation of the agent as suppositories (per rectum) not only enhances the immunogenicity and protective properties of the vaccine, but also reduces the frequency of its application and makes more convenient for patients to use. PMID- 20364671 TI - [Antiviral activity of sulfated polysaccharide from the brown algae Laminaria japonica against avian influenza A (H5N1) virus infection in the cultured cells]. AB - The antiviral activity of the sulfated polysaccharide fucoidan from the brown sea algae Laminaria japonica against infection caused by highly virulent avian influenza virus (Alduck/Novosibirsk/02/05, H5N1) in the sensitive pig embryo kidney cell cultures was studied. Fucoidan was ascertained to have no cytotoxic activity and to show virucidal activity against influenza A/H5N1 virus. When given at concentrations of 50 to 500 microg/ml, fucoidan protected the cell cultures from the cytopathogenic activity of influenza virus in a dose of 0.01 TCID50/1.0 ml and was able to suppress influenza A/H5N1 virus production within 24 hours of infection when prophylactic and therapeutic-and-prophylactic treatment regimens were used. PMID- 20364672 TI - [Stabilization of peroxidase conjugates used in enzyme immunoassay systems to detect Ebola and Marburg virus antigens]. AB - The time course of changes in the activity of solutions of horseradish peroxidase conjugates with immunoglobulins against Ebola and Marburg fevers was studied in the presence of different components. The series of the conjugates of ELISA kits for the detection of Ebola and Marburg virus antigens, which were prepared on the basis of the designed stabilizing solution, preserved at less than 90% of its baseline activity during 10 months at a storage temperature of 2 to 8 degrees C. PMID- 20364674 TI - [Clinico-laboratory associations of candidial infection persistence in diabetes mellitus]. AB - Population heterogeneity of Candida spp. in feces of patients with diabetes mellitus (DM) demonstrated in our earlier studies prompted to focus on the persistence of candidial infection depending on demographic characteristics of the patients and clinical features of DM. We examined 64 patients with DM and 40 practically healthy subjects aged 20-60 yr. The seeding rate (%) of short-lived (emerged on day 0 or 1) and long-lived (emerged on both days 0 and 1) of Candida spp. cultures was determined. The short-lived fraction of microorganisms most frequently occurred in patients below 50 yr without clinico-laboratory signs of DM and the history of candidiasis (coincidence rate 75.0%, p < 0.001). The long lived fraction was characteristic of patients with the history of candidiasis having DM of less than 5 yr in duration and glycated hemoglobin over 7.8 mmol/l without complications taking oral hypoglycemic agents (80%, p < 0.001). Candida spp. were totally absent in patients with late diabetic complications, duration of disease over 5 yr, glycated hemoglobin level below 7.8%, and candidiasis-free history. It is concluded that clinico-laboratory characteristics and demographic factors determine persistence of Candida spp. in feces of DM patients. PMID- 20364673 TI - [Polymorphism of cytokine genes in the development of Helicobacter pylori infection]. AB - The purpose of this work was to study morphological features of gastric mucosa depending on polymorphism of IL-l1beta and IL-1RN genes in children with chronic gastritis infected with different strains of Helicobacter pylori 0. We examined 106 children with HP-associated gastritis. The results suggest association of mucosal inflammation with T allele in polymorphous C-511T locus of IL-1beta (beta2 = 14,006; alpha = 0.001). agA + strains of HP were more frequently identified in patients with erosive ulcerative defects of gastric mucosa than in children with superficial gastritis (p < 0.05). The possibility of gene typing to form a group of patients with the unfavourable post-eradication clinical course for the prevention of duodenal ulcer and stomach cancer is discussed. PMID- 20364675 TI - [Monitoring detection and treatment of new patients with pulmonary tuberculosis]. AB - We estimated results of detection and treatment of TB patients registered in 2006 in 15 regions of RF under supervision of the Central Research Institute of Tuberculosis. The fraction of sputum positive patients increased in comparison with 2005. It ranged from 77.1% in Orel region to 35.2% in Astrakhan region. The primary MDR rate varied significantly from 2.5% in the Republic of Mordovia to 14.7% in Mary El (estimated level 5%). The frequency of efficient chemotherapy (evaluated from sputum microscopy data) increased in 8 regions and decreased in 7 ones. The efficiency varied from 69.0 to 81.1% in 9 regions (recommended level for 2007 68.5%). It amounted to 68.5% or higher (based on sputum culturing data) in Republics of Kalmykia and Tatarstan, Nizhny Novgorod, Saratov and Ul'yanovsk regions. TB mortality rate in 2006 exceeded the acceptable level of 2.5% in 13 regions and the frequency of refusals to continue chemotherapy was higher than 5% recommended for 2010 by the Global Fund Target Project in 10 regions. The efficiency of treatment in sputum-positive patients was frequently evaluated by X ray in 3 regions with poorly organized microbiological services. TB treatment efficiency estimated from cavity closure was higher than 60% in 10 regions; it the remaining ones it varied from 36,3% (Nizhny Novgorod) to 52.2% (Vladimir). The system of evaluation being tested permits to accurately register new TB patients, objectively estimate effectiveness of their treatment, and reveal causes of its failure. Also, it makes possible corrections of therapeutic strategy on a trimestrial basis instead of postponing them till the end of the year. Introduction of cohort analysis combined with supervision of responsibility regions by specialists of relevant research institutions would increase efficiency of TB control in each subject of Russian Federation. Supervisory management appears to be an efficacious tool for monitoring implementation of the TB control Program. PMID- 20364676 TI - [Disturbances in the cytokine system and oxidative stress in patients with chronic cardiac insufficiency]. AB - A total of 99 patients with systolic chronic cardiac insufficiency (CCI) of NYHA functional class II-III (ejection fraction below 45%) were examined to evaluate cytokine activities, levels of oxidative stress markers and BNP fragment of brain natriuretic peptide. Patients aged 65-75 yr (group 2) had much higher levels of IL-1-beta, FNO-a, and malonic aldehyde than 26-56 year-old ones (group 1). The latter had a higher catalase activity. It is concluded that elderly patients with CCI develop more pronounced inflammatory reaction manifest as elevated C-reactive protein level, activated cytokine system, and endothelial dysfunction due to a longer history of the disease, higher frequency of ischemic etiology of CCI, and impaired NO-production in endothelium. PMID- 20364677 TI - [Comparative study of magnesium salts bioavailability in rats fed a magnesium deficient diet]. AB - The purpose of this study was to compare efficiency of compensation of alimentary Mg deficiency after administration of 12 organic and 8 inorganic magnesium salts and to evaluate the ability of vitamin B6 to accelerate their effect. Two hundred eighty rats were placed on a Mg-deficient diet (Mg content (15 mg/kg) and demineralized water for 7 weeks. Twelve control rats were fed a basal diet (Mg content 500 mg/kg). Starting from day 49 of the Mg-deficient diet, the rats were given magnesium salts (50 mg magnesium and 5 mg pyridoxine per kg): Mg chloride, Mg sulphate, Mg oxide, M nitrate, Mg thiosulphate, Mg hydrophosphate, Mg carbonate, Mg trisilicate, Mg (L-, D- and DL-) aspartate, Mg (L- and DL-) pyroglutamate, Mg succinate, Mg glycinate, Mg orotate, Mg taurate, Mg lactate or their combination with vitamin B6 (5 mg/kg b.w.). Erythrocyte and plasma Mg levels were measured by spectrophotometry following the colour reaction between Mg and titanium yellow. Mg L-aspartate compensated for magnesium deficit more effectively and faster than all other salts. Mg chloride showed the highest efficiency among inorganic magnesium salts. Both Mg chloride and Mg L-aspartate in combination with vitamin B6 caused statistically significant compensation of magnesium deficit. PMID- 20364678 TI - [The role of peptides in aging control: results and prospects of research]. AB - The paper summarizes results of long-term research designed to elucidate mechanisms of aging and evaluate efficacy of peptide bioregulators for the prevention of age-specific pathology. Peptides obtained by up-to-date methods in Russia, U.S.A., U.K., Germany, Italy, Spain, and France are reviewed. A molecular model is proposed to describe complementary interactions of short-chain peptides with gene promoters underlying initiation of protein synthesis. Prospects for the use of peptide bioregulators to prevent premature aging of the employable population in Russia are discussed. PMID- 20364679 TI - [Gastrointestinal stromal tumours: clinico-morphological features, pathogenesis and modern treatment strategies]. AB - Gastrointestinal stromal tumours (GIST) are the commonest mesenchymal tumours of gastrointestinal organs accounting for 1-3% of all gastrointestinal neoplasms and almost 5% of all soft tissue sarcomas. Most GIST (95%) express transmembrane receptor KIT or CD117, CD34 (70%), vimentin (80%), specific smooth muscle and neurogenic markers (with different frequency). Up to 85% of the stromal tumours have mutations in the KIT gene (exones 9, 11, 13, 17) and 3-18% in the PDGFRA (platelet-derived growth factor receptor-alpha) gene (exones 12, 14, 18). Mutations are absent in 5% of KITand PDGFRA genes. Mutational status, mitotic index, size and location of the tumour are the most informative criteria for the choice of treatment strategy and prognosis of the disease. PMID- 20364680 TI - [Involvement of hemoglobin in the therapeutic action of blood ultraviolet irradiation]. AB - The objective of this work was to study the mechanism of therapeutic action of extracorporeal ultraviolet irradiation of circulating blood and to evaluate the possibility of its application to combined treatment of patients with acute coronary syndrome. It was shown that ultraviolet irradiation causes photodissociation ofoxyhemoglobin thereby altering the oxygen-carrying function of the blood and improving oxygen supply to cells and tissues. The UV-induced modification of blood properties not only prevents tissue hypoxia but also triggers a cascade of metabolic processes. Taken together, these effects have beneficial influence on the clinical course of cardiovascular and other diseases. PMID- 20364681 TI - [Potentiation of anti-ischemic and anti-anginal action of nitrates by hydrogen sulfide balneotherapy in patients with angina of effort]. AB - The objective of this comparative study was to evaluate effects of nitrosorbid (NS) and hydrogen sulfide-based balneotherapy (HSB) applied alone or in combination for the treatment of patients presenting with angina of effort. It was shown that long-term HSB therapy enhances the anti-anginal and anti-ischemic action of NS in such patients. The authors argue that prolonged HSB-based maintenance therapy in combination with nitrates prevents habituation to these preparations and potentiates their beneficial therapeutic effect. PMID- 20364682 TI - [Investigation of antioxidative effects of phytotherapy combined with vetoron treatment in patients presenting with arterial hypertension]. AB - Biochemical effects of phytoinhalation and oral administration of biologically active additives containing beta-carotene (e.g. vetoron) are evaluated with special reference to changes in lipid peroxidation. Systemic analysis of the mechanisms of antioxidative effects of phytotherapy demonstrated the leading role of activation of vegetative homeostasis-regulating centres and central stress limiting systems as well as direct action of antioxidative ingredients comprising the formulation. The study showed that combination of phytotherapy and vetoron allowed the overall antioxidative efficiency of these treatments to be considerably increased due to their action on different targets. It is concluded that the proposed method promotes effectiveness of combined rehabilitative treatment in patients with arterial hypertension due to correction of disturbed lipid peroxidation. PMID- 20364683 TI - [Sanatorium-and-spa treatment of children with mucoviscidosis and pancreatic lesions]. AB - Over 5 years ago, the Yunost' sanatorium, Essentuki, and the Russian Centre of Mucoviscidosis, Moscow, began to jointly implement a rehabilitation program for children with mucoviscidosis. The data obtained made it possible for the first time to propose incorporation of drinking carbonate mineral water in the combined sanatorium-and-spa treatment of such patients. The new method allowed effectiveness of this therapy to be improved by 16-18%. PMID- 20364684 TI - [Seasonal variations of nucleic acid content in an experiment on non pharmacological correction of the hepatic function]. AB - This experiment was preformed on an animal model of CCl4 hepatitis using 320 Wistar rats. The animals underwent combined effect of saprogel and a magnetic field during different seasons. It was shown that non-medicamentous treatment of experimental CCl4 hepatitis had the most pronounced beneficial effect on the synthetic liver function in the winter time. An appreciable suppression of the hepatic function was documented in the spring. PMID- 20364685 TI - [The influence of exercise therapy on the psychological status of women presenting with osteoporosis]. AB - The objective of the present study was to evaluate effectiveness of correction of the psychological status of postmenopausal women suffering primary osteoporosis (OP) by means of exercise therapy. Diagnosis of OP was verified by dual energy X ray absorptiometry. The degree of depression was assessed using the CES-D questionnaire and that of reactive anxiety by the C.D. Spielberger and Yu.L. Khanin method. A visual-analogue scale was used to obtain self-assessment of the patients' health and pain intensity. Physical rehabilitation was shown to cause reduction of reactive anxiety and alleviate pain syndrome. As a result, the quality of the patients' life improved regardless of OP severity. However, beneficial effect of exercise therapy was apparent only in patients presenting with mild and moderately severe anxiety/depressive disorders but was lacking in more serious cases. PMID- 20364686 TI - [Combination of clinical homeopathy and dynamic neurostimulation for the restoration of male sexual function]. AB - The impairment of sexual function diagnosed in approximately one third of apparently healthy men dictates the necessity of their rehabilitative treatment. The objective of the present study was to evaluate effectiveness of the combination of clinical homeopathy and dynamic electrical neurostimulation (DENS) for the restoration of disturbed sexual function. The study demonstrated that the efficiency of the proposed method in terms of dynamics of subjective and objective improvement surpasses that of isolated application of clinical homeopathy or DENS when compared against the use of placebo. PMID- 20364687 TI - [Prophylaxis of traumatism and physical methods for the correction of adaptive processes in football players during training exercises]. AB - The present study was focused on etiopathogenetic aspects of injuries and diseases of the locomotor system (LS) in football players. Up-to-date methods for the prevention of LS tissue overstrain during the execution of physical exercises are described. Adequate application of preventive measures allowed biochemical and physiological characteristics of these tissues to be improved. Specifically, the frequency of muscular spasms and pain was reduced to 1.9% compared with 22.8% in the control group. PMID- 20364688 TI - [Mechanism of strategic management of a sanatorium-and-spa facility under current economic conditions]. AB - The existing system of management of sanatorium-and-spa facilities constitutes a major economic risk factor under current socio-economic situation. One of the most important conditions for the sustainable continuation of activities of a sanatorium-and-spa institution is its adaptability to the changing economic environment. Those health care providers are likely to have an advantage in new conditions that offer a larger scope of specialized services, simultaneously reduces their costs and prices, introduce resource-saving technologies, and stimulate motivation of the medical personnel. PMID- 20364689 TI - [Prospects for the development of health resort and recreational resources in southern Siberia]. AB - Long-term monitoring natural health remedial factors of southern Siberia provided materials for the comparative evaluation of bioclimatic characteristics of sanatorium-and-spa facilities in major health and recreational areas of this region. The most promising localities for climatic balneotherapy, tourist and recreational activities have been identified at the territory of the Altai-Sayan mountain system. The database of sanatorium-and-spa facilities, health and recreational sites located in this region is presented. The rational exploitation of mountainous landscapes including strict constraints on nature use activities is recommended as a basis for the further development of recreational industry. PMID- 20364690 TI - [Influenza and acute respiratory viral infections. A role of a polyclinic therapist in timely diagnosis and treatment]. AB - The paper emphasizes a role of a local therapist in the timely detection and treatment of acute respiratory viral infections. It shows a certain difficulty in the differential diagnosis of acute respiratory disease and influenza. Attention is given on a need for a well-defined program to correct drug therapy, regimen, and diet at home. Indications for hospitalization are specified. Temporary disability periods are determined depending on the patient's general condition, age, and occupation. The significance of the currently available methods for nonspecific and specific prevention is shown. PMID- 20364691 TI - [Factors contributing to gallstone formation and their interaction]. AB - AIM: to study factors contributing to gallstone formation and to elucidate their relationship. SUBJECTS AND METHODS: The examination of 230 patients with various hepatobiliary abnormalities used dynamic ultrasonic cholecystography, multifractional duodenal intubation, followed by a microscopic study and determination of the physicochemical properties of bile. Enzyme immunoassay was employed to measure the peripheral blood levels of gastrin, insulin, T3, T4, thyroid-stimulating hormone, cortisol, and growth hormone. RESULTS: All the patients were found to have signs of an early (gallstone pre-formation) stage of cholelithiasis. Decreased emptying of the gallbladder and its hypotonia and altered bile physicochemical properties were ascertained to be poor predictors of possible gallstone formation. CONCLUSION: Correlation analysis has shown the important role of hormonal factors in the formation of lithogenic bile. PMID- 20364692 TI - [Methodological approaches to the expert appraisal of therapeutic care quality in chronic cholecystitis]. AB - AIM: to develop a technology for assessing the quality and consequences of medical care in chronic noncalculous cholecystitis by an expert--a therapist, a gastroenterologist. MATERIALS AND METHODS: One hundred and ninety-three cases of expert appraisal of medical care quality in chronic noncalculous cholecystitis were analysed. The expert appraisal of the quality of medical care was carried out by comparing with that of the reference - the standard for the diagnosis and treatment of chronic noncalculous cholecystitis. To detect the defects correlated with the negative consequences of medical care, the authors calculated statistical criteria for assessing an association between the indices of accumulated informative value and the consequences of rendered medical care. RESULTS: According to the assessed quality of medical care, the patients were divided into two groups: (1) 163 patients with negative consequences of delivered medical care; (2) 30 patients with its positive consequences (a control group). The identifed drawbacks that significantly determined negative outcomes had a certain distribution in the groups by their frequency. The analysis provided calculations of the accumulated informative value index for each case individually for the processes of diagnosis and treatment, by drawing up the boundaries of proper and improper medical care delivered to patients with chronic noncalculous cholecystitis. CONCLUSION: The formulated criteria of positive consequences of medical care are oriented to the differential diagnosis of biliary tract pathology, to differentiated approaches to treatment analysis, and to the likely outcomes of exposure to medical and diagnostic actions on the pathological process, which allows an expert to predict its further dynamics and consequences of rendered medical care. The algorithmized expert appraisal of cases of medical care delivery makes it possible to objectivize the opinion and conclusions of an expert. PMID- 20364693 TI - [Role of a local therapeutic service in the timely identification, treatment, and rehabilitation of patients with coronary heart disease]. AB - Local polyclinic therapists' long experience in timely identifying, treating and rehabilitating patients with coronary heart disease (CHD) is analyzed. A local therapist's attention is given to diferent course types--the clinical manifestations of CHD. The principles of continuity in the work of a therapist and a hospital: possibilities of extrahospital treatment are denoted; indications for hospitalization are specified. Rehabilitative measures include psychotherapy sessions in addition to drug, dietary, and exercise therapies. Continuity in the work of a therapeutic unit and a sociomedical expert commission contributes to the elaboration of clearer criteria for determining the degree of working capacity loss. PMID- 20364694 TI - [Intoxication by alcohol and substitutes: prehospital diagnosis and emergency medical care]. AB - The paper considers the pathogenesis, clinical picture, and diagnosis of acute intoxications with alcohol and substitutes, and its prehospital medical care. It details an emergency team's tactics in patients with the above conditions. PMID- 20364695 TI - [The clinical efficiency and safety of iodide-bromine balneotherapy in patients with coronary heart disease concurrent with chronic obstructive pulmonary disease]. AB - AIM: to evaluate the efficiency of iodide-bromine balneotherapy (IBB) in patients with coronary heart disease (CHD) concurrent with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Sixty-six patients with CHD, Functional Class HII stable angina on exertion concurrent with mild and moderate COPD were examined. Group 1 included 36 patients with CHD concurrent with mild and moderate COPD (a study group); Group 2 consisted of 30 patients (a control group). The groups were matched for age, gender, and concomitant abnormality. The patients from both groups undergone a complex clinical and instrumental study (clinical and biochemical study, echocardiography, 24-hour ECG monitoring, EchoCG, external respiration function (ERF) test. In both groups, CHD and COPD were treated by the generally accepted standards, Group I patients were additionally given IBB at a water temperature of 37 degrees C; the concentration of iodine and bromine was 10 15 and 30-40 m/I, respectively; the duration was 10-15 min for 2 consecutive days, followed by a rest day or every second day; the course comprised 10-12 sessions. RESULTS: After the course of IBB, there were significant reductions in the number of anginal attacks and the dose of nitrates weekly, the number of episodes of supraventricular and ventricular premature contractions, producing no impact on the cardiac conduction system. The duration of silent myocardial ischemia and the degree of ST-segment depression significantly reduced. No significant changes were obtained in the control group. ERF examination confirmed the safety of IBB used in patients with CHD and COPD. CONCLUSION: IBB has a beneficial antiischemic activity in patients with CHD concurrent with COPD, without producing a negative impact on ERF. PMID- 20364696 TI - [Efficacy of ivabradine in combination therapy for complicated acute coronary syndrome in patients with type 2 diabetes mellitus]. AB - AIM: To study the effect of ivabradine (coraxan, Servier) as part of combination therapy on the clinical manifestations of acute left ventricular failure (ALVF) in Braunwald class II-IIIB unstable angina in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: Thirty-six T2DM patients (mean age 56 + 4.3 years) with a diagnosis of acute coronary syndrome were examined. Eighteen healthy individuals were examined as an age- and gender-matched control group. Metabolic, hemodynamic, and electrophysiological parameters were studied in all the patients on hospital stay days I and S. RESULTS: Ivabradine used in combination therapy for unstable angina caused reductions in the clinical manifestations of ALVF, heart rate, the number of myocardial ischemic episodes. In the ivabradine-treated patients, left ventricular ejection fraction showed a significant trend for increase. No adverse reactions were recorded. CONCLUSION: Ivabradine therapy demonstrated antiischemic and antianginal efficiencies and a good tolerability, without leading to the development of tolerance and without being followed by the development of the withdrawal syndrome. PMID- 20364697 TI - [Analysis of the gene polymorphism of matrix metalloproteinase-2 and -9 in patients with coronary heart disease]. AB - AIM: To analyze the gene polymorphisms of matrix metalloproteinase-2 and -9 in patients with coronary heart disease (CHD). MATERIALS AND METHODS: The influence of single nucleotide polymorphism in the promoter region of the gene of matrix metalloproteinase (MMP)-2 at position -1306 and that of MMP-9 at position -1562 on the development of complications was studied in 181patients with atherosclerosis by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of amplification products. RESULTS: A significant genotype increase with enhanced MMP-9 gene transcriptional activity was found in the patients aged 55 years inclusively who had been diagnosed as having myocardial infarction as compared with an older age group and, on the contrary, a rise in the MMP-2 genotype with a high promoter activity in the older age group. CONCLUSION: The findings suggest that the functional polymorphism in the promoter region of the MMP-2 and MMP-9 genes plays a certain role in the development of acute coronary events. PMID- 20364698 TI - [Evaluation of fludarabine-containing regimens versus immunochemotherapy for chronic lymphocytic leukemia]. AB - AIM: to analyze the efficacy of RFC (rituximab, fludarabine, and cyclophosphan), FCM (fludarabine, cyclophosphan, and mitoxantrone), and FC (fludarabine and cyclophosphan) treatment programs in patients with chronic lymphocytic leukemia (CLL) in an open-labeled comparative controlled investigation. MATERIALS AND METHODS: The paper presents the authors' results of treatment in patients with progressive CLL in 2002 to 2007. The study included 229 patients, of them 78 patients received the RFC program, 72 had the FCM program, and 79 had the FC one. RESULTS: With the use of RFC, a clinically significant therapeutic effect was obtained in 96% of the patients, a complete remission (CR) was in 80% of the primary patients and in 53% of the pretreated patients. When the FCM program was applied, a positive response was noted in 93% of the patients, CR was seen in 75 and 42% of the primary and pretreated patients, respectively. In the treatment of FC, the total effect was 80%, CR was in 41 and 14% of the primary and pretreated patients, respectively. CONCLUSION: Comparative analysis of an objective response to therapy has indicated that the effectiveness of the RFC significantly exceeds that of the FCM and FC programs, without enhancing toxicity, which allows he RFC regimen to be regarded as the program of choice in therapy for CLL. PMID- 20364699 TI - [Regulation of erythropoiesis in patients with suppressed hematopoiesis during mountain climatic treatment]. AB - AIM: to estimate the regulation of erythropoiesis and the coagulation system in patients with suppressed hematopoiesis in a mountain hospital (3200 m above sea level). SUBJECTS AND METHODS: The investigation included 12 patients with aplastic anemia (AA) and 10 with idiopathic thrombocytopenic purpura (ITP). Blood was received at a Bishkek hospital, then on days 20 and 40 of stay in the mountains. The authors studied erythropoietin (EPO) by enzyme immunoassay (Protein Contour kit, Russia), serum ferritin (SF) by immunoradioassay (Immunotech kit, Czech Republic), hypoxia-inducible factor-1alpha (HIF-1alpha), homocysteine (HC), hepcidin, endothelin (ET), and thrombomodulin (TM) by sandwich enzyme immunoassay, by applying monospecific antisera and monoclonal antibodies against relevant antigens (IDG Int Inc, USA). RESULTS: On staying in the mountains, there was a gradual increase in the content of hemoglobin in patients with AA and ITP. On day 40, in keeping with higher hemoglobin (Hb) levels, both groups showed a decrease in HIF-1alpha concentrations to the normal values (from 8.2 to 4.5 pg/ml). Due to the anemic syndrome, baseline EPO was increased by 5-7 times in the patients from both groups. On days 20-40, the content of EPO showed a 1.3-2.5-fold increase. In AA, HC was almost 3 times greater than the normal values; in ITP, it was 1.5-fold increased. On day 20 and during the patients'stay in the mountains, the level of HC remained in the normal range in both groups. CONCLUSION: Hypoxic hypoxia positively affects a number of hematological parameters, by normalizing erythropoiesis (Hb, EPO, and HIF-1alpha), iron metabolism (SF), and the coagulation system (HC, ET, and TM). PMID- 20364700 TI - [Brachial artery responsiveness in patients with systemic lupus erythematosus and scleroderma systematica]. AB - AIM: to evaluate brachial artery (BA) endothelial vasomotor function in patients with systemic lupus erythematosus (SLE) and scleroderma systematica (SDS), by using noninvasive studies. Subjects and methods. Sixty-five patients, including 25 with SLE, 20 with SDS, and 20 with atherosclerosis (AS) obliterans of lower extremity peripheral arteries, were examined. A control group consisted of 30 apparently healthy individuals matched with the study groups for gender and age. The ultrasound technique described by D. Celermajer, et al. was employed to evaluate endothelium-dependent vasodilation (EIVD). Endothelium-independent vasodilation (EIVD) was assessed by the nitroglycerin test. The coefficient of BA susceptibility (CS) to reactive hyperemia was calculated. RESULTS: In all study patient groups EDVD values were significantly lower (7.3 +/- 1.35% in SLE, 6.91 +/- 0.9% in SDS, and Z7.64 +/- 1.9% in AS; p < 0.05) than in the controls (11.23 +/- 1.1%). An adequate vascular bed response was found in 5 (20%) patients with SLE and in 2 (10%) patients with SDS. A paradoxical vasoconstrictor response to reactive hyperemia was encountered in 9 (36%) patients with SLE, 11 (55%) with SDS. In all the study groups, the patients had normal EIVD with lower CS. In SLE and SDS, CS was decreased than that in the controls. The impaired BA responsiveness in SLE and SDS significantly correlated with the duration and activity of the disease, Raynaud's syndrome, capillaritides, mean blood pressure, renal lesions, as well as with the laboratory values of the activity of inflammation and blood lipid composition. CONCLUSION: In SLE and SDS, there was a reduction in EDVD and EIVD, as well as paradoxical vasoconstriction. CS is an independent indicator of endothelial dysfunction with the normal values of EIVD. Impaired BA responsiveness was associated with the course of systemic inflammation and severe lesion of organs. PMID- 20364701 TI - [Significance of the markers of endothelial dysfunction and hemorheological disorders for assessing the activity and prognosis of chronic glomerulonephritis]. AB - AIM: to define the clinical value of changes in blood rheological properties and renal endothelial function in patients with hematuric and nephritic forms of chronic glomerulonephritis (CGN) and to ascertain whether the indices under study can be applied to assess the activity (progression) of nephritis and used as a prognostic criteria. SUBJECTS AND METHODS: Sixty-one patients, including 30 with hematuric nephritis (Group 1) and 31 with nephrotic nephritis (Group 2), were examined. A control group consisted of 12 healthy individuals. The rheological properties of blood, such as its viscosity; kinetics of spontaneous aggregation and disaggregation of red blood cells in shear flow; their deformability; urinary excretion of functionally active von Willebrandt factor (WF), a plasminogen activator inhibitor type 1 (PAl-1); urine total fibrinolytic activity (UTFA), activity of urinary urokinase-type plasminogen activator (UPA) were studied. RESULTS: The patients with CGN were found to have signs of impaired blood rheological properties (increased viscosity, an accelerated rapid phase of erythrocyte aggregation, increased strength of erythrocyte aggregates) and vascular endothelial dysfunction in the microcirculatory bed, among other factors, increased urinary excretion of functionally active WF, PA-1, which correlated with the activity of CGN. Data were obtained on the negative impact of the level of urinary PAl-1 excretion, red blood cell aggregation on the prognosis of CGN regardless of its form, the markers of endothelial damage/activation. Low urokinase activity and decreased red blood cell deformability in parallel with higher diurnal proteinuria are of poor prognostic value for hematuric nephritis. CONCLUSION: The findings illustrate two ways of the involvement of the endothelium in the mechanisms contributing to the development of tubular interstitial fibrosis, namely: endothelial dysfunction and as a substrate that links the processes of immune inflammation, hemorheology, and fibrinolysis/proteolysis in the kidney. The regularities revealed by clinical and laboratory comparison suggest that the indices under study may be used to determine the prognosis of the disease and may serve as a basis for the application of treatments aimed at correcting the detected disorders. PMID- 20364702 TI - [Role of free radical oxidation in the development of cardiovascular events in chronic renal failure]. AB - AIM: to refine a role of free radical oxidation (FRO), anemia, and endothelial dysfunction in the development of cardiovascular events in patients with chronic renal failure (CRF) at diferent stages of the disease. SUBJECTS AND METHODS: Eighty-six patients, including 46 (53%) women and 40 (47%) men with Stages II-IV CRF, were examined. The patients' mean age was 43.6 +/- 14 years. Echocardiography, measurements of the blood levels of hemoglobin, albumin, cholesterol, and uric acid, and determination of blood electrolytic composition were made. Blood creatinine concentrations in the group averaged 0.3 mmol/l. Glomerular filtration rate (GFR) calculated from the Cockroft-Goult formula averaged 33.96 +/- 13 ml/min; the duration of CRF was 9.3 +/- 1.6 years. Anemia was detected in 46 (53%) patients. Iron metabolism was estimated from serum ferritin levels. Special studies involved determination of FRO--malondialdehyde (MDA) and the activities of catalase and superoxide dismutase (SOD) in plasma and serum. The plasma concentrations of endohelin-1 (ET-1), thromboxane A2, and prostacyclin were measured by radioimmunoassay. Results. The higher concentrations of MDA and the decreased activities of catalase and SOD, i.e., FRO, correlated with the progression of renal failure. There were also increases in the levels of ET-1 and thromboxane A, and a reduction in the concentration of prostacyclin as blood creatinine levels elevated. Left ventricular hypertrophy was found in 43 (50%) of the 86 patients. Its severity depended on the decrease of creatine phosphokinase and the severity of anemia and arterial hypertension. There was a stable correlation between the changes in left ventricular myocardial mass, MDA levels, and catalase and SOD activities. CONCLUSION: The higher level of MDA and the lower activities of catalase and SOD in patients with CRF, which correlate with diminished renal function, confirm that the disease is closely associated with FRO, that, by aggravating anemia and endothelial dysfunction, affects the magnitude of morphological and functional changes in the cardiovascular system in patients with CRF patients. PMID- 20364703 TI - [Diagnosis of cryptococcal encephalitis in a patient with mature B-cell lymphoblastic leukemia]. AB - Fungal meningoencephalitides are one of the most menacing infectious complications in hematologic cancer patients in the presence of myelotoxic agranulocytosis. Due to diagnostic difficulties, mortality in these cases can be as high as 100%. The causative agent of cryptococcosis is Cryptococcus neoformans; damage to the brain arachnoid membranes and substance is diagnosed in 70-90% of cases. Unlike bacterial meningitis, the meningeal symptoms typical of cryptococcal meningoencephalitis are not characteristic. The paper gives a case of successful treatment for cryptococcal meningoencephalitis in the presence of agranulocytosis, the diagnosis of which is based on the detection of abnormal MR signal foci by magnetic resonance imaging and identification of the cryptococcal antigen-glucuronoxylomannan in spinal fluid. PMID- 20364704 TI - [The Faculty Therapy Clinic in the formation of clinical teaching of internal medicine: on the occasion of the 250th anniversary of the I. M. Sechenov Moscow Medical Academy]. AB - The V. N. Vinogradov Faculty Therapy Clinic of the Imperial Moscow University (IMU) (then Moscow State University--I. M. Sechenov Moscow Medical Academy) was opened under this name in 1846 simultaneously with the Surgery Clinic on Rozhdestvenka Street. The paper shows the continuity of the idea for bedside clinical teaching, whose need was clearly realized just by S. G. Zybelin and which was first done in practice by his follower and the first Director of the Clinical Institute, IMU, F. G. Politkovsky, as well as that of specific forms of implementing of this idea. It is shown that just early internal medicine teaching provided the principles that were stated by M. Ya. Mudrov and that subsequently formed the basis of a course taught at the Department of Faculty Clinic. The original teaching of a theoretical course without a clinic one at the Department of Particular Pathology and Therapy, which was stipulated by the 1835 Charter, gradually lost its importance as clinical teaching was formed. The succession of the Clinical Institute and the Faculty Clinic was also shown in the staff the director of the newly-opened Clinic and Therapy Department Professor was A. I. Over, M. Ya. Mudrov's favorite disciple and the last Director of the Clinical Institute; the adjuvant teacher at the Therapeutic Department of the Clinical Institute was K. Ya. Mlodzeyevsky. This all permits the V. N. Vinogradov Faculty Therapy Clinic to be regarded a competent descendant of the first clinical institutes. In conclusion, there is a clinical analysis of division of an internal medicine course into faculty and hospital courses at the present stage and prospects for teaching therapy are discussed. PMID- 20364705 TI - [Duodenal intubation: present view (on the occasion of the 100th anniversary of duodenal intubation)]. AB - The paper presents the proceedings on the Symposium on the Occasion of the 100th Anniversary of Duodenal Intubation" at the 9th Congress of the Scientific Society of Gastroenterologists of Russia. Particular emphasis is laid on the significance of the clinical and experimental studies-based scientific discovery made by V. A. Galkin and A. S. Chechulin--the Galkin-Chechulin effect (the 1957 priority) for the detection and treatment of prestone stages of cholelithiasis. The steps for improving the bile examination techniques at duodenal intubation (V. A. Galkin, L. S. Korzyuk, V. A. Maksimov, A. A. Ilyechenko) are described. Duodenal intubation as the method of choice for bile examination is proposed to be included into the mandatory diagnostic standards. PMID- 20364706 TI - [Chronic gout: causes, clinical manifestations, treatment]. AB - Why chronic gout, that is mostly a well diagnosed and controlled disease if it is timely and systematically treated with allopurinol, becomes a topical public health problem following 50 years after the introduction of pathogenetic therapy with xantine oxidase inhibitors is under consideration. The principles of rational therapy for chronic gouty arthritis are outlined. PMID- 20364707 TI - [Arterial stiffness as a predictor of cardiovascular events in coronary heart disease]. AB - To date, there is much evidence confirming that impaired arterial elastic properties have a direct impact on prognosis in patients with chronic renal failure, arterial hypertension, or diabetes mellitus in the general population and in the elderly. At the same time, in most cohort studies the manifestations of coronary heart disease (CHD) constitute about two thirds of developed cardiovascular events (CVE); the value of arterial stiffness after CHD manifestations has not been conclusively ascertained. There are various opinions on the mechanism and pattern of this association. Rigidity of large vessels may be a marker of cardiac artery lesion, on the one hand, and promote deterioration of myocardial ischemia in the presence of coronary atherosclerosis, on the other. This review of literature discusses the pathogenetic and clinical aspects of the impact of stiffness of the great vessels on the development of CVE. PMID- 20364708 TI - [Left ventricular noncompaction concurrent with bronchoectatic disease complicated by secondary AA-amyloidosis with renal involvement]. AB - The paper describes a clinical case of congenital cardiomyopathy (left ventricular noncompaction) concurrent with secondary amyloidosis and renal involvement that develops at the outcome of long existing brochoectatic disease. PMID- 20364709 TI - [Screening of yeast-producers of melanin in the Antarctic terrestrial biotopes]. AB - Now it is considered, that melanin is promising for application in medicine and pharmacology. Since black yeast were found in polar regions before, we have carried out screening of yeast-producers of melanin in the Antarctic biotopes. Dark pigmented microorganisms are revealed in 30% of samples from terrestrial biotopes at the western coast of the Antarctic peninsula, on islands of the Argentina archipelago (Galindez, Skua, Corner, Barchans, Irizar, Uruguay, Cruls, Three little pigs, King-George), and also on the neighbouring islands Petermann, Jalour, Berthelot, Darboux and Lippmann. In the Antarctic lichens the occurrence frequency of dark pigmented microorganisms, their total number and biodiversity are significantly higher, than in other Antarctic biotopes. Coal-black yeast are found on the crustose and bushy lichens on vertical rocks, they occur less often in soil, their quantity made 1 x 10(2) - 6 x 10(3)/g of a sample. Coal-black pigments were isolated from two Antarctic strains of yeast. These pigments are identical to melanin according to a complex of specific chemical tests, that is also confirmed by the character of UV-spectra (220-230 nm) and absorption spectra in the visible area (400-800 nm). The output of synthesized pigment/g in strain 36 made more than 10% of biomass amount. So, the yeast synthesizing intensively melanin are revealed in the Antarctic terrestrial biotopes. PMID- 20364710 TI - [Probiotic properties of industrial strains of lactobacilli and bifidobacteria]. AB - Lactic acid bacteria and bifidobacteria were isolated from the samples of dry microbial substance "Vivolac" and identified. The lactic acid bacteria were identified as Lactobacillus acidophilus. L. delbrueckii subsp. bulgaricus, L. paracasei. Bifidobacteria belonged to the species Bifidobacterium animalis. Manifestation of biological activity of all studied strains was investigated. It was shown, that adhesive activity of the studied strains depended on the genus of the strain: lactobacilli manifested medium adhesiveness to buccal epithelium (medium adhesive index 2.07-2.26), bifidobacteria manifested high adhesiveness (medium adhesive index 4.11-4.76). Antagonism against pathogenic and opportunistic reference strains was manifested to a greater extent to Pseudomonas aeruginosa. Lactobacilli and Bifidobacteria were resistant to aminoglycosides. Sensitivity of the studied strains to antibiotics did not depend on the genus and species of microorganism. Lactobacillus and Bifidobacterium strains were capable to survive in gastric juice and at different concentration of bile, which is promising for development of probiotic preparations on the basis of these strains. PMID- 20364711 TI - [Chemical characterisation of structural components of Rahnella aquatilis lipopolysaccharides]. AB - The studies of lipopolysaccharides (LPS) of eight Rahnella aquatilis strains, isolated from different sources have shown that they contain both S- and R-types of molecules. This fact is evidenced by the presence of high-molecular fraction of O-specific polysaccharides (O-PS) and low-molecular fraction of core oligosaccharides. The predominant monosaccharides of core oligosaccharides were glucose, galactose. The presence of only one high-molecular fraction O-PS was a characteristic feature of all investigated strains. The predominant monosaccharides of O-PS were galactose, glucose, mannose, rhamnose and fucose. 3 hydroxytetradecanoic (48.9-93.1%), dodecanoic (2.9-12.1%), tetradecanoic (4.1 25.3%) and hexadecanoic (2.8-15.3%) acids have been obtained in lipids A of LPS depending on the strain. The presence in lipid A of R. aquatilis of only 3 hydroxytetradecanoic acid which is characteristic of Enterobacteriaceae proves the correct ascribing of the isolated strains to this family. PMID- 20364712 TI - [Influence of probiotic drugs BPS-44 and BPS-L on the acid-base balance in the calf blood]. AB - Research of influence of the probiotic drugs BPS-44 and BPS-L on the state of the antioxidation system by means of experiments on young animals of cattle. The authors have established that the effective functioning of antioxidation system of cattles' blood (a decrease of the products of lipids' peroxidation level and activation of the primary enzymes of antioxidation defense) is provided by the prophylactic use of these probiotics. The most evident positive influence on the antioxidation system of cattle young animals was made by the associate drug BPS-L that causes the essential decrease of malonic dialdehyde, activation of catalase and increase of antioxidation factor value. PMID- 20364713 TI - [Biodegradation of surface-active substances of Acinetobacter calcoaceticus K-4]. AB - A capacity of microorganisms of different taxonomic groups to assimilate surface active substances (surfactants) of Acinetobacter calcoaceticus K-4 as a single source of carbon and energy has been established. It was shown that A. calcoaceticus K-4 cannot use its own surfactants as a source of carbon nutrition. The use of biocide formalin in concentration of 0.1% permits to prolong the term of preservation of A. calcoaceticus K-4 surfactants to 3.5 months without a loss of their surfactant and emulsiying properties. PMID- 20364714 TI - [Chlorate reduction by immobilised bacteria in continuous conditions]. AB - Chlorate reduction by the strain Aerococcus dechloraticans TGS-463 immobilized on the corncob under flow conditions has been studied. It has been established that under growth in the medium with chlorate the increase of the dilution rate (D) results in the lower efficacy of the process, i.e., a higher concentration of residual chlorates in the medium and a lower rate of chlorate reduction. The optimal D for chlorate reduction ranges from 1.12 to 1.5 hour(-1). PMID- 20364715 TI - [Contexts of initiation codons of tobamo- and potexvirus genes translation]. AB - The contexts of translation initiation codon (the nucleotide sequences surrounding the AUG) have been analyzed by computer in 15 tobamoviruses (45 genes) and 22 potexviruses (110 genes). The results obtained indicate both high key similarity and some differences between viral and eukaryotic AUG contexts. The similar features are: the localization of coinciding nucleotides near the start codon (in -3... +18 positions), purines presence in position (-3... +18) and guanine in position +4 (+4G) relative to codon AUG as well as the similarity of viral translation contexts to corresponding context sequences of vertebrates (16.9-52.4%), monocot (21.9-41.2%) and dicot plants (39.3-74.3%). The distinctive features of viral translation initiation contexts are a high frequency of +5C, 5Y and +10R components as well as a broad variation of context elements between various viruses and/or genes. So, the frequency of +5C varied between 0% (TGB1 genes) and 100% (Re genes), the -5Y--from 22% (TGB2 genes) to 86% (Mp genes), the +10R--between 22% (TGB2 genes) and 93% (Mp genes), and the frequency of eukaryotic Kozak contexts varied from 5% (TGB2 genes) to 87% (Mp genes). The test proposed to compare a similarity between translation initiation contexts and their known consensus sequences are discussed. PMID- 20364716 TI - [Identification of a pandemic influenza virus A/H1N1 by real-time PCR]. AB - The WHO approved protocol of pandemic influenza virus A/H1N1 identification by the method of one-step RT-PCR was adopted. The cost of research was decreased due to adoption of RNA purification method and utilizing of the common enzyme systems for RT-PCR. PMID- 20364717 TI - [Prospects of antimicrobial drugs development on the basis of new synthetic substances]. AB - The literature data concerning different chemical substances effects on microorganisms is considered in this paper. Synthetic substances screening is one of the promising ways of searching for new highly effective antimicrobial drugs. Previously those synthetic substances were not used in the clinical practice separately or in combinations as pharmacological products. PMID- 20364718 TI - The NBNA: continuing the push for health-care reform. PMID- 20364719 TI - Feelings of powerlessness and the elderly. PMID- 20364720 TI - Stress and coping among elderly African-Americans. AB - The purpose of this descriptive correlation was to examine the relationship between the amount of psychological stress experienced and the methods of coping with stress among elderly African-Americans. Demographic variables (age, gender, marital status, education, and occupation), personal resources (health, religion, and social support), and the effects of perception of racial discrimination were included to determine the relationship among the variables and to predict the perceived amount ofpsychological stress and the methods of coping. Subjects were males and females, who were community dwellers, between 65 to 88 years of age. Each subject completed four questionnaires: a Demographic Personal Data Questionnaire, the Short Portable Mental Status Questionnaire, the Stokes/Gordon Stress Scale, and the Ways of Coping Questionnaire. The data were analyzed by computing measures of central tendency, frequency, percentile, and measures of variability. Correlation and stepwise regression were used for predictions and to test null hypotheses. The findings indicated that elderly African-Americans experienced psychologically stressful events in their lives such as concerns for the world, slowing down, physical limitation, financial concerns, and not enough time with their children and grandchildren. PMID- 20364721 TI - Applying the Theory of Planned Behavior to reporting of forced sex by African American college women. AB - Forced sex is a public health issue affecting many college women. Despite physical and mental health consequences, and multiple prevention programs on college campuses, most sexual violence goes unreported (Fisher, Daigle, Cullen, & Turner, 2003). The purpose of this research was to determine the significant attitudes and beliefs that are associated with reporting of forced sexual experiences. Guided by the Theory of Planned Behavior (TPB), the study used a predictive exploratory design to explore the association of intention to report forced sex with attitudes and beliefs (Ajzen, 1991). A convenience sample of 144 African-American women who were attending a private college in the south completed a survey. Women who expressed more favorable attitudes towards reporting, perceived reporting as being supported by important referents, and perceived more control over reporting, reported stronger intentions to report forced sex. The analysis supported the utility of TPB in predicting the intention to report forced sex by African-American college women. Theoretically significant and clinically relevant prevention strategies should incorporate important referents, address salient beliefs, and determine ways to increase perceived behavioral control. PMID- 20364722 TI - Knowledge, beliefs and practices of African-American nurses regarding genetics/genomics. AB - In an effort to increase the awareness of genetics among African-American nurses, a pilot study was conducted with members of the National Black Nurses Association (NBNA) in order to assess the interest, knowledge, and practice of African American nurses regarding genetics and to identify program needs. Self administered surveys were distributed to a convenience sample of 77 African American nurses (N=77) attending the 2006 Annual Conference of the National Black Nurses Association (NBNA) in Hollywood, Florida. Measures of central tendency and frequencies were used to analyze the data. Over half the sample (56%) self reported their knowledge of genetics as being only fair or poor; however, 56% were interested in genetic awareness training, and 93.5% were willing to participate in planned genomic education. An unexpected finding was that 77.9% believed that genetic tests could be used to discriminate against minorities. Although this sample reported limited genetics/genomic knowledge, their interest in genetics training and the incorporation of genetics into daily practice was high. These data can be used to support the development and implementation of culturally appropriate genetic awareness training. Challenges for the organization include identification of the type of venue to use for genetic/genomic awareness training and identification of resources and partnerships to support NBNA members in gaining genetic awareness training. PMID- 20364723 TI - Ethnic minority baccalaureate nursing student academic dismissal: a description of the antecedent academic characteristics. AB - Dismissal for academic reasons from a baccalaureate nursing (BSN) program is a phenomenon that has rarely been discussed in the literature, and, as a result, little is known about the academic characteristics of the students who are dismissed. Presently, minority students that have been admitted to BSN programs are less likely to graduate from their respective nursing programs than White BSN students are, but whether or not ethnic minority student attrition is due to academic dismissal has not been clearly described. In addition, the antecedent academic characteristics that may identify minority BSN students at high risk for academic dismissal are not fully understood. Thus, the primary purpose of this study was to describe the academic characteristics ofa sample of minority BSN students who experienced academic dismissal. A secondary purpose was to compare ethnic minority BSN students who were dismissed with a sample of ethnic minority BSN students who were academically successful. The results revealed that ethnic minority BSN students who were dismissed for academic reasons tended to have low scholastic and nursing aptitudes, and that nursing aptitudes were higher among ethnic minority BSN students who were academically successful. PMID- 20364724 TI - Exploration of African-American women's infant feeding choices. AB - It is well documented in the literature that breastfeeding is more beneficial for infants and mothers than is formula feeding. Yet, African-American women are least likely to initiate and continue breastfeeding compared to other ethnic groups. Few studies have examined African-American women's infant feeding choices from the women's perspectives. Therefore, the purpose of this exploratory study was to examine African-American women's infant feeding choices with individual narrative interviews at 3 weeks postpartum. Five African-American women participated. After coding and analyzing the narrative interviews, three major themes with sub-themes emerged that identified influencing factors on participants' choices and their opinions about other women who chose formula. The women willingly shared their rationales for their infant feeding methods. In an effort to develop and implement culturally appropriate interventions and to increase breastfeeding rates in this population, further exploration of infant feeding choices from the women's perspectives is needed. PMID- 20364725 TI - A survey of a HBCU's senior year nursing students' perception of the HIV/AIDS phenomenon: a follow-up study. AB - This study was a follow-up to a previous study that was done among first semester nursing college students at a historically Black college and university in northeastern United States. The original intent was to ascertain their perceptions and knowledge of various aspects of the Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) phenomenon. It involved an anonymous survey questionnaire featuring yes and no answers, a Likert scale, and qualitative response questions concerning prevention behavior. Respondents were asked whether HIV/AIDS could make an individual "sick enough to die", whether they thought that wearing a condom would diminish their feeling during the sexual experience, and whether they would insist their partners use a condom. The original study consisted of 68 students. The follow-up study,four years later, consisted of the 20 remaining nursing students from the original cohort and was undertaken with the intent to appraise their knowledge level and to ascertain whether their attitudes towards the use of condoms as a way to prevent HIV/AIDS and STDs had changed. Findings from this follow-up study indicated that educational attainment of the respondents did not translate into a change in attitudes about responsible sexual behavior. Further findings may suggest that intensive HIV/AIDS education begin at an earlier phase in a students'education. Along with the basics of HIV/AIDS education, students need to learn to be respectful of each others' health and wellbeing. It is essential that a nurturing and protective environment exist so that young women are not afraid of the consequences related to asking partners to wear condoms during sexual encounters. PMID- 20364728 TI - Irritable bowel syndrome: recent progress in pathophysiology, diagnosis and management? PMID- 20364727 TI - Disabilities in older African-American women: understanding the current state of the literature. AB - The purpose of this review sought to address the following question: What does the current literature report regarding older African-American women with disabilities? A search of PubMed database was done for research on African American women, ages 45 years and older, who have a disability. Sixty-one articles were reviewed and categorized into groups according to themes. The term disability was only defined in one of the studies. Overall, the studies reviewed revealed racial and ethnic disparities among African-American women with disabilities that included increased hospital days, poor health days, hospitalizations, being functionally totally dependent, and having increased primary and repeat amputations when compared to their White counterparts. PMID- 20364726 TI - Expanding the scope of nursing research in low resource and middle resource countries, regions, and states focused on cervical cancer prevention, early detection, and control. AB - Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death in women worldwide. There are significant disparities in cervical cancer incidence and mortality globally as well as in the United States. The most significant global disparities in cervical cancer incidence and mortality are reported in low resource and middle resource countries, regions, and states. This report provides an overview of cervical cancer epidemiology and etiology, and identifies "gaps" in the nursing literature specific to cervical cancer prevention and control worthy of consideration by nurses within the practice setting. PMID- 20364729 TI - Development of a novel mineral based haemostatic agent consisting of a combination of bentonite and zeolite minerals. AB - BACKGROUND: Haemorrhage remains the greatest threat to life on the battlefield, accounting for half of all deaths. Over the past decade the US army has widely studied new technologies for stopping sever haemorrhages and has introduced an effective zeolite based haemostatic agent. In this paper the bio-stimulatory effect of burned radioactive lantern mantles powder as well as two minerals; bentonite and zeolite are presented. METHODS: In this experimental study, 50 male Wistar rats were divided randomly into 5 groups of 10 animals each. Following anaesthesia, animals' tails were cut off at a thickness of 5 mm by using a pair of surgical scissors. No intervention was made on the animals of the 1st group. The 2nd to 5th group received topical nonradioactive lantern mantle powder, radioactive lantern mantle powder, Bentonite mineral or a mixture of bentonite zeolite minerals respectively. After treatment with above mentioned agents, the volume of blood loss was measured using a scaled test-tube. The bleeding time (BT) and clotting time (CT) were also measured using a chronometer. Analysis of variance (ANOVA) was used for comparing the means of each parameter in the 5 groups. RESULTS: The volume of blood loss, bleeding and clotting time in control animals were 4.39 +/- 1.92 ml, 112.10 +/- 39.60 sec and 94.9 +/- 54.26 sec respectively. In the 2nd group, in which the animals were treated with a nonradioactive lantern mantle, the volume of blood loss, bleeding and clotting time were 2.34 +/- 0.35 ml, 54.50 +/- 14.77 sec and 22.9 +/- 6.54 sec, respectively. In the 3rd group, in which the animals were treated with a radioactive lantern mantle, the volume of blood loss, bleeding and clotting time were 1.50 +/- 0.58 ml, 37.10 +/- 7.81 sec and 33.5 +/- 15.76 sec respectively. In the 4th group, in which the animals were treated with bentonite mineral, the volume of blood loss, bleeding and clotting time were 1.81 +/- 0.62 ml, 55.70 +/- 16.73 sec and 45.9 +/- 32.17 sec, respectively. In the 5th group, in which the animals were treated with a mixture of bentonite-zeolite minerals, the volume of blood loss, bleeding and clotting time were 1.31 +/- 0.60 ml, 34.50 +/- 4.65 sec and 24.2 +/- 4.61 sec, respectively. CONCLUSION: To our knowledge, this is the 1st study to investigate the alterations of bleeding and clotting time following the use of lantern mantle powder as well as bentonite or the mixture of bentonite zeolite minerals. The results obtained in this study clearly show the significant alterations in the volume of blood loss as well as the bleeding or clotting time following the topical use of the mixture of bentonite-zeolite minerals. Controlling the generation of heat was a great achievement in development of the novel haemostatic agent produced in this study. PMID- 20364731 TI - Detection of atherosclerosis by ankle brachial index: evaluation of palpatory method versus ultrasound Doppler technique. AB - BACKGROUND: Peripheral Arterial Disease [PAD], a manifestation of systemic atherosclerosis, is highly prevalent both in community studies and in primary care practice. Estimation of ankle brachial index [ABI] by ultrasound Doppler is the standard screening method for the detection of atherosclerosis in PAD patients. A low ABI is associated with increased risk of stroke or transient ischemic attack, ischemic heart disease and lower extremity gangrene. Though prevalence is high, physician and patient awareness of the condition is low. Primary care physicians are not well versed with the use of Doppler. Initial cost of the equipment is another adverse factor in low income countries. Detection of ankle systolic pressure by palpatory method may offer a cheap, simple and useful alternative approach in office care settings for early detection of disease. This may lead to the use of risk reduction strategies to avoid significant future morbidity and mortality. METHODS: The sample size of 230 participants was identified. Patients were divided into control (100 cases), high risk asymptomatic (100 cases) and symptomatic groups (30 cases). Ankle systolic pressure was measured by digital palpation of foot arteries and by the gold standard Doppler technique in all patients in the three groups. PAD was defined by an ABI of < 0.9. RESULTS: In control group, mean +/- SD value of ABI was 1.0115 +/- 0.08167 by Doppler method versus 0.9923 +/- 0.08609 by palpatory method (p = 0.1), in high risk asymptomatic group, 0.9838 +/- 0.08878 versus 0.9608 +/- 0.10377 (p = 0.13) and in symptomatic group, 0.9302 +/- 0.14064 versus 0.9088 +/- 0.13274 (p = 0.12). Against the more precise Doppler method, palpatory method was equally good in detecting the PAD positive cases. CONCLUSION: Early diagnosis of PAD in primary care practice by manual palpation of foot arteries is a reliable method to identitfy the population at risk and may lead to aggressive preventive therapies. PMID- 20364730 TI - Urodynamic findings in female patients reporting with lower urinary tract symptoms. AB - OBJECTIVE: The study has been undertaken to determine the reproducibility of lower urinary tract symptoms in female patients after urodynamic investigations. DESIGN: A Descriptive study with retrospective analysis of data. SETTING: Combined Military Hospital Rawalpindi and Armed Forces Institute of Urology, Rawalpindi. METHODS: Fifty consecutive women with a primary history of urinary incontinence were interviewed on a standard urinary incontinence questionnaire. They underwent structured clinical pelvic examination, along with cough stress test. Post void residual urine was measured. This was followed by a urine routine examination to exclude any urinary infection. Later these patients underwent a combination of urodynamic tests to predict their final diagnosis. The tests performed were filling cystometry and leak point pressures. RESULTS: The clinical diagnosis was found to have a variable reproducibility on urodynamic investigations. Clinical stress incontinence translated as genuine stress incontinence in 61.5% of the cases. Patients with isolated symptoms of stress incontinence had an incidence of detrusor instability up to 33.3%. For the symptoms of urgency and urge incontinence, the diagnosis was reproducible in up to 50% of the cases. In cases of mixed symptoms, 20% patients were found to have stress incontinence and 33.3% cases were found to have an unstable bladder, whereas in 46.6% of the cases no objective abnormality was found on urodynamic investigations. CONCLUSION: Urodynamic investigations should be performed in female patients with lower urinary tract symptoms, especially if irreversible procedure, e.g., surgery is being contemplated. PMID- 20364732 TI - A comparative analysis between non-mesh (Bassini's) and mesh (Lichtenstein) repair of primary inguinal hernia. AB - BACKGROUND: The groin hernia repair is one of the common operations in general surgery. The optimum repair method is under debate and the best mode of repair is yet to be decided. This study is conducted to compare the results of open non mesh (Modified Bassini's) and Lichtenstein's mesh repair of primary inguinal hernia in terms of recurrence, postoperative complications and quality of life in the long-term. METHODS: This retrospective comparative analytical study includes 840 patients of which 40 patients were excluded from the study due to various reasons. The remaining 800 patients with unilateral primary inguinal hernia, above 16 years of age, operated during January 2000 to December 2007 in a teaching hospital are included in the study. Of the total number, 392 patients (49%) underwent Lichtenstein mesh repair, while remaining 408 patients (51%) were operated by modified Bassini's suture technique. Follow up was conducted 1, 5, 8 and 15 days; 1, 2, 6, 24 and 36 months. RESULTS: The recurrence rate and postoperative pain were significantly low in Lichtenstein mesh repair compared to open non-mesh repair by modified Bassini's technique (p < 0.001). Recurrence occurred in 8 (2.0%) out of 392 patients those with Lichtenstein mesh repair. On the other hand 29 (7.1%) patients with Bassini's repair reported recurrence within 3 years time. CONCLUSION: Mesh repair of inguinal hernia is much superior to non-mesh repair in terms of recurrence and postoperative chronic pain. PMID- 20364733 TI - Management outcome of closed femoral shaft fractures by open Surgical Implant Generation Network (SIGN) interlocking nails. AB - BACKGROUND: Many hospitals in our country lack surgical expertise and operating room facilities like image intensifier and fractures table to carry out closed interlocking nails (ILN) in femoral shaft fractures. But availability of Surgical Implant Generation Network (SIGN) interlocking nails & nailing instrumentation have made open ILN of these fractures possible at very basic level of our health care system. We have carried out open SIGN nailing in patients with closed fractures of shaft femur without the use of image intensifier. Result for fracture union was evaluated both clinically and radio-logically, and graded at 8 months (32 weeks) after treatment by Thoressen's criteria. METHODS: An experimental study of open SIGN nailing was carried out on 47 patients with fractures shaft of femur who had been admitted to our tertiary care hospital from January 2006 to December 2007. Inclusion criteria were adult patients older than 16 years with closed fractures of the shaft femur, and have presented within a week of the injury, and have not had any previous surgical treatment for the fracture. Malnourished patients and patients with open, pathological fractures and non union cases were excluded from the study. A standard protocol was followed on all patients, which is describing below. The data obtained was analysed using SPSS. RESULTS: The union rate was 97.83% in open nailing at 32 weeks after surgery and the Mean +/- SD time to union was 19.65 +/- 5.19 weeks (ranges from 16-32 weeks).We obtained excellent results in 39 patients (83.33%), good in 4 patients (8.50%), fair in 3 patients (6.38%) and poor in one (2.12%). CONCLUSIONS: The open SIGN nailing, without the use of image intensifier, for treatment of closed fractures of shaft femur achieves excellent result in term of fracture union. Results obtained are comparable to the results of closed interlocking nailing, requires less expertise and resources, and its use is recommended for long bones fracture care at the very level of our health care system. PMID- 20364734 TI - Spermatogenesis following discontinuation of calcium channel blocker amlodipine in rats. AB - BACKGROUND: The calcium channel blockers are commonly associated with male infertility. Long-term administration of such drugs has been shown to suppress spermatogenesis. The present study was designed to determine the effects of cessation of calcium channel blocker (amlodipine) medication on spermatogenesis. METHODS: The study was carried out in the Department of Physiology, in collaboration with Department of Pathology, Army Medical College, and National Institute of Health, Islamabad from April 2007 to March 2008. Thirty male rats were divided into two groups A and B each containing 15 rats. Group A rats were given distilled water (vehicle) whereas group B rats were given amlodipine by oral gavage for 50 days. After 50 days, amlodipine/distilled water was withdrawn. The rats were left for recovery to take place for another 50 days of drug withdrawal period. Testes were removed in all the rats and sectioned. The sections were stained with haematoxylin and eosin and examined microscopically. Results were analyzed using SPSS version 13. RESULTS: Fifty days after drug withdrawal, there were statistically insignificant differences in mean tubular diameter and height of germinal epithelium between amlodipine treated and vehicle treated groups. CONCLUSION: Spermatogenesis in amlodipine treated rats does not differ significantly from spermatogenesis in vehicle treated rats after 50 days of drug withdrawal period. PMID- 20364735 TI - Knowledge, attitude and practice of private practitioners regarding TB-DOTS in a rural district of Sindh, Pakistan. AB - BACKGROUND: Tuberculosis is prevailing in both urban and rural areas of Pakistan. Knowledge, attitude and practice (KAP) of private practitioners (PPs) regarding tuberculosis management have been reported only in urban areas of Pakistan. This survey was conducted for the first time in a rural area of Sindh, Pakistan. METHODS: This survey was conducted in January 2007 at Thatta, a rural district of Sindh, Pakistan. Study subjects were twenty-two allopathic qualified (MBBS) doctors of district Thatta, who were practicing in private setups for at least last one year. Before TB-DOTS training PPs had filled the KAP questionnaire regarding tuberculosis (TB) diagnosis and management through DOTS. Survey data was analysed through SPSS version 11.05 software. RESULTS: On average, five TB suspects per month were seen by each PP. Only 14% of PPs advised sputum microscopy solely for pulmonary TB diagnosis, while 86% of PPs used different combination of tests (chest x-ray/sputum microscopy/ESR/tuberculin test) for TB diagnosis. Over 40% PPs did not prescribe TB treatment regimen according to TB DOTS category. Majority PPs (85%) did not follow the treatment through sputum microscopy and instead relied on clinical improvement and x-ray clearance. Nearly 60% of TB patients at PPs clinic did not show compliance to the TB treatment and none of PPs were following the retrieval of default cases. CONCLUSIONS: A gross lack of PPs knowledge and right practice regarding TB diagnosis and management through DOTS was identified and needed to be addressed through providing DOTS training. PMID- 20364736 TI - Comparison between efficacy of MDI+spacer and nebuliser in the management of acute asthma in children. AB - BACKGROUND: Due to changing evidence on efficacy of MDI+spacer as compared to nebuliser, two types of managements were going on in our Day unit, depending on the presence of different medical professionals. We wanted to find out the evidence of the best practice from within our unit, and then to formulate guidelines based on it for the management of paediatric acute asthma. METHODS: We isolated 54 cases of children suffering from acute asthma attack from admissions during Oct 2004-March 2005 within the age range of 3-14 yrs. We categorised them into four classes of mild, moderate, severe and life threatening acute attack depending on its severity and then separated them in two groups. Group I received salbutamol Via MDI+spacer and Group II received salbutamol via nebuliser. Our outcome measure was time to clinical improvement and duration of hospital stay. RESULTS: We didn't find any major difference between the two groups, moreover MDI+spacer was better than nebuliser for the treatment of severe acute asthma attack in children. CONCLUSION: Our study supported and confirmed the evidence that MDI+spacer is least as effective as nebuliser in the management of acute asthma in children. PMID- 20364737 TI - Reverse radial artery flap for soft tissue defects of hand in pediatric age group. AB - BACKGROUND: To highlight the usefulness of reverse radial artery flap in covering various soft tissue defects of hand in paediatric age group. METHODS: A total of 16 reverse radial artery flaps were utilized in a period of three years to cover various soft tissue defects of hand for paediatric age group patients. The age ranged from 5-18 years. The two common causes of soft tissue defects in this series were mechanical trauma and fireworks trauma with five cases in each group. Three of the cases were burn victims and other two presented with earth quake injuries. One patient had wound because of road traffic accident. Soft tissue defects of palm were covered with this flap in eight cases while in three cases it was wrapped around the thumb. First web space defects were covered with this flap in two cases. Two cases required coverage of amputation stump at transmetacarpal level and yet another required a big flap to cover the soft tissue defects at palm, dorsum and thumb. Donor site was covered with split skin graft in all cases but one, which was closed primarily. RESULTS: We had partial loss of flap in one case. Grafted donor sites healed uneventfully and were quite acceptable to the patients in due course of time. CONCLUSION: Reverse radial artery flap has a quite long arc of rotation which brings it great ease to cover the soft tissue defects of various areas of hand like palm, dorsum, first web space and thumb. PMID- 20364738 TI - Outcome of sutureless manual extra capsular cataract extraction. AB - BACKGROUND: Cataract surgery is constantly evolving. Purpose of this study was two folds: to estimate visual outcome and evaluate safety and efficacy of sutureless manual extra-capsular cataract extraction. METHODS: This was a prospective, interventional case series, using sutureless manual extra capsular cataract surgery technique from June 2004 to January 2007 at Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex Peshawar. Patients included in the study were those having operable cataracts. All those having corneal co-morbidities extensive enough to block visualisation of posterior segment details, chronic adenexal diseases, long standing glaucoma, advanced diabetic eye disease and retinal detachment evident on B-Scan ultrasonography were excluded from the study. After thorough examination and investigation all the patients were operated upon by a single experienced surgeon using the same technique. Their visual outcome was analysed. The patients were followed for a period of six weeks. RESULTS: A total of 1500 cataract surgeries were carried out, of which 1211 (80.74%) patients completed six weeks of follow up. Seven hundred and fifty seven (62.51%) had an uncorrected good visual acuity (6/6-6/18) on 1st post-op day, 1131 patients (93.40%) had an uncorrected visual acuity of 6/6-6/18 on 6th week follow up. Mean surgically induced astigmatism at 6 weeks was 0.3 dioptres. CONCLUSION: Sutureless manual extra capsular cataract surgery is a safe and effective technique. It offers faster wound healing and quick rehabilitation of cataract patients at any level of community eye care setting. PMID- 20364739 TI - Chick feed technique versus standard chop technique in micro incision cataract surgery. AB - BACKGROUND: The important factor for improving the cataract surgery is reduction in size of corneal incision. Small incision results in less induced astigmatism, and faster visual rehabilitation. METHODS: An analysis of 100 eyes of 80 patients operated for phacoemulsification through micro incision by standard chop technique (50 eyes) in group-I, and chick feed technique (50 eyes) in group-II is presented. All of the patients were operated on by posterior limbal corneal incision under topical or sub-tenon anesthesia. In all patients, posterior chamber bag fixation foldable intraocular lens implantation was performed through 1.4 to 1.6 mm corneal incision. RESULTS: Forty patients (80%) out of fifty operated in group-2 had an over all visual recovery of 6/12 to 6/9 on day one post operative, as compared to group-1 where only ten (20%) patients out of fifty had visual recovery of 6/12 to 6/9. In the second week, out of 37 patients operated in group-2, thirty patients (81%) had visual acuity 6/6. Similarly in second week post operative, out of forty three patients operated in group-1, only eighteen patients (41.8%) had V/A of 6/6. Maximum visual recovery was observed in early post operative phase in group-2 patients. CONCLUSION: The chick feed technique has been proved to be the most compromising method in micro incision cataract surgery, as compared to standard chop method, due to its capability of working on low energy and negligible vacuum. PMID- 20364740 TI - Emergency peripartum hysterectomy: frequency, indications and maternal outcome. AB - BACKGROUND: Emergency Peripartum Hysterectomy (EPH), although rare in modern obstetrics, remains a life saving procedure in cases of severe haemorrhage. The aim of present study was to review the frequency, indication, associated risk factors, maternal morbidity and mortality associated with emergency peripartum hysterectomy in a private sector teaching hospital. METHODS: This was a retrospective review carried out from August 2003 to September 2008. Main outcome measures were frequency, indications, associated risk factors and maternal morbidity and mortality associated with Emergency Peripartum Hysterectomy. RESULTS: The frequency of emergency peripartum hysterectomy over a study period was 0.42%. Mean age and parity of patients was 30.9 +/- 5.0 years and 4.52 +/- 1.8 respectively. The mean gestational age at the time of delivery was 36 +/- 3.4 weeks. Nine (42.9%) patients had previous history of caesarean delivery. Main indication for EPH were rupture uterus 7 (33.3%), uterine atony 6 (28.6%), morbid adherence of placenta 5 (23.8%) and severe bleeding from placental bed in 3 (14.3%) patients. All woman required blood transfusion, 11 (52%) require ICU admission, 81% were anaemic, 3 (14.3%) developed DIC, 4 (19%) pulmonary oedema, febrile illness 6 (28.6%) and wound disruption was seen in 3 (14.3%). The maternal mortality occurred in 4 (19%) cases. CONCLUSION: Frequency of emergency peripartum hysterectomy is high in our set up. High parity, rupture uterus, increase number of caesarean deliveries and abnormal placentation was identified as risk factors for EPH. High frequency of maternal morbidity and mortality was observed in the present study. PMID- 20364741 TI - Ethno-botanical studies from Northern Pakistan. AB - BACKGROUND: In this research paper efforts have been made to document the ethno botanical knowledge of important plant species found in Northern Pakistan. It includes Thandiani, Galiat, Kaghan, Swat, Buner, Dir, Chitral and Northern Areas of Pakistan. The area has many climatic and vegetation zones or biomes. Locals residing in mountainous areas belonging to various ethnic groups are traditionally utilizing plants over many generations; these ethnic groups have their distinct life style, belief, traditions and cultural heritage. METHODS: Plant collection and data regarding traditional uses in various areas of Northern Pakistan has been done periodically in different flowering /fruiting seasons. Locals of old age belonging to various ethnic groups were personally interviewed for establishing uses of plants. Photography is done for easy identification and habitat recognition. Collected plant specimens and seeds were preserved. Plant species were dried, mounted, identified and authenticated. RESULT: 135 genera belonging from 66 families of angiosperms and gymnosperms were studied and described.76 species were known to have traditional and ethno botanical uses. Plants have been utilized for many generations. Ethnic groups have distinct life style and have different economic uses for these plants. Due to unsustainable exploitation of natural habitats scarcity of drug plants has occurred. As consequence some species are depleting and may become extinct in near future, e.g. Morchella esculenta, Colchicum lueteum and Viola serpens are just a few of these. CONCLUSION: Although some sporadic information is available about the flora of this region but very little documented record of the ethno-botanically important plants has been established. It is expected that this research paper will be beneficial for students, researchers, farmers, foresters and general public. On the basis of data obtained it is concluded that ethno-botanical Flora of Northern Pakistan is quite rich and is diverse, due to the difference in altitude, climate and other topographic conditions. PMID- 20364742 TI - Estimation of heritability of familial hypercholesterolemia among 335 family members of five hypercholesterolemic probands of Pakistani population. AB - BACKGROUND: Familial hypercholesterolemia is an autosomal dominant disorder, caused by mutation in Low-density lipoprotein receptor (LDL-R) gene. METHODS: Cross-sectional study conducted to recruit the population of Karachi-Pakistan, screened for familial hypercholesterolemia. A total of 1523 hypercholesterolemic individuals have taken part in the study, five were found to be familial hypercholesterolemia. Their lipids profile was estimated and a family pedigree was drawn. RESULTS: Parent-offspring correlation, coefficient of linear regression, and heritability is calculated by using SPSS 12.0. A significant positive correlation of cholesterol was found among parents and their offspring (r = 0.511, p = 0.01, n = 76). Coefficient of linear regression analysis also showed that parents-offspring relationship was highly significant at p < 0.01 with b = 0.438. Relationship between Father-Son, Father-Daughter, Mother-Son and Mother-Daughter were highly significant with b = 0.794, 0.41, 0.766 and 0.56 respectively. CONCLUSION: The heritability among the parents and their offspring showed that genetic factors are major determinant of the familial resemblance in serum cholesterol among the Pakistani population living in the metropolitan area of Karachi. PMID- 20364743 TI - Is glycemic control in patients with type-2 diabetes in Rawalpindi improving? AB - BACKGROUND: Glycaemic control is critical for managing diabetes and related complications. Considering high prevalence of Diabetes in Pakistan, our study aimed to assess the status of glycaemic control in Type-II Diabetics by measurement of HbA1c from 2005-2007 at Rawalpindi. We also evaluated changes in its trends in relation with sex and age. METHODS: It was a retrospective analysis of data from Clinical Pathology Laboratory, Army Medical College, Rawalpindi during 2005-2007. A total of 2875 patients, aged 24-70 years, taking oral hypoglycaemic agents, were included. HbA1c was measured by using Human kit. International Diabetes Federation guidelines, < or = 6.5%, 6.6%-8.4% and > or = 8.5% were used to classify patients into good, fair and poor control categories. RESULTS: The number of patients (n = 2875) tested for HbA1c increased from 904,974 to 997 during 2005-2007. The patients had an age of 48 +/- 13 years and comprised of 54% males and 46% females. Improvement in patient's glycaemic control among the three categories during 2005 to 2007 was as follows: good (41% vs 47%), fair (38% vs 40%) and poor (21% vs 13%) respectively. The average HbA1c values improved from 7.25 % in 2005 to 6.69% in 2007 (p < 0.05). Overall, males (45%) and youngest age group (53%) patients had good diabetic control. CONCLUSION: Glycaemic control improved in diabetic patients from 41% to 47% during 2005-2007 at Rawalpindi. Males, especially the youngest patients comprised majority of good control population. For effective disease management and optimal HbA1c values, a combined effort by the patient and physician is required. PMID- 20364744 TI - A reappraisal of contributing factors leading to shunt infection. AB - BACKGROUND: Central nervous shunt infection (CNSI) is a cause of significant morbidity, causing shunt malfunction and chronic ill health. It can also lead to prolong hospital stay. The aim of this study was to look into the factors responsible for neurosurgical shunt infection and measures to prevent them. METHOD: This retrospective case study was done with nonrandomized convenience sampling. We studied 121 patients who underwent neurosurgical shunt operations during year 1994 to 1999. These patients received pre, per and post operative antibiotics to combat shunt infection. Study design was retrospective case study with non randomized convenience sampling. RESULT: Out of 121 patients, 65 patients were females and 56 males. The total number of shunts procedures performed in these patients was 151. Ninety-seven patients operated once for shunt procedure. Eighty-three (83) patients underwent ventriculo-peritoneal shunt, 10 patients underwent lumbo-peritoneal shunt, 3 had ventriculo-pleural shunt and 1 had ventriculo-atrial shunting done. Three patients developed shunt infection, only one had true primary infection. All were adults with male to female ratio of 2 to 1 and in all of them shunt was inserted first time. CONCLUSION: Strict aseptic technique and prophylactic use of antibiotics have critical role in the prevention of shunt infections. PMID- 20364745 TI - Impact of renal transplantation on erectile dysfunction due to chronic renal failure in male patients. AB - BACKGROUND: Erectile dysfunction can be defined as the persistent inability of man to achieve penile erection and maintain it sufficient for satisfactory coitus. The objectives of this study were to find out the impact of successful renal transplantation on the degree and frequency of erectile dysfunction. METHODS: Thirty patients of end stage renal disease that were on regular haemodialysis and candidates of renal transplantation of age range 20-55 years were included in the study after getting informed consent. Erectile functions were assessed by history, examination, investigations and international index of erectile function (IIEF) before and 3 and 6 months after renal transplantation, other information regarding disease and patient were collected in the performa. RESULTS: Out of thirty patients 14 (46.6%) patients had sever erectile dysfunction while 16 (53.3%) patients had moderate erectile dysfunction in the pre renal transplantation period. After three months of renal transplantation 15 (50%) had severe erectile dysfunction, 6 (20%) patients moderate erectile dysfunction and 9 (30%) patients mild erectile dysfunction. After six months 11 (36.6%), 10 (33.3%) and 8 (26.6%) patients had severe, moderate and mild erectile dysfunction respectively. CONCLUSION: There was improvement in 40%, no change in 53.3% and deterioration in 6.6% patients in the erectile functions after getting renal transplantation for end stage renal disease. PMID- 20364746 TI - Hepatocellular carcinoma (HCC) and diagnostic significance of A-fetoprotein (AFP). AB - BACKGROUND: Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. METHODS: To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan 2004 to Dec 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. RESULTS: In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421 +/- 59 microg/ml (range 157-4019 microg/ml) in males and 163 +/- 32 microg/ml (range 101-2341 microg/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 microg/ml (range 67-4019 +/- 59 microg/ml,), whereas in females it was 396 +/- 42 microg/ml (range 21-2341 microg/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. CONCLUSION: It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and monitoring treatment regiments. In addition, AFP is also an indicator of HCC risks mostly in patients with cirrhosis and HCV/HBV infections. PMID- 20364747 TI - Swiss roll operation for giant fibroadenoma. AB - BACKGROUND: Fibroadenoma 5 cm or more is called giant fibroadenoma. Giant fibroadenoma can distort the shape of breast and causes asymmetry, so it should be excised. There are several techniques for excision of giant fibroadenoma. In our technique we remove them through cosmetically acceptable circumareolar incision to maintain the shape and symmetry of breast. The objectives were to assess the cosmetic results of Swiss roll operation for giant fibroadenoma. The study was conducted for six years from January, 2002 to December, 2007. METHODS: Seventy patients of giant fibroadenoma were included in this study. They were diagnosed on history and clinical examination supported by ultrasound and postoperative histopathological examination. Data were collected from outpatient department and operation theatre. Swiss roll operation was performed under general anaesthesia. RESULTS: Mean tumor size was 6.38 cm. Three cm and 4 cm incisions were used for tumour < or = 6 cm and > 6 cm in size respectively. Skin closed with Vicryl 3/0 subcuticular stitches. Sixteen out of 70 patients had no scar while others hadminimal scar. All patients had normal shape and symmetry of breast. On histopathology fibroadenoma was confirmed. CONCLUSION: Giant fibroadenoma should be removed through cosmetically acceptable cicumareolar incision especially in unmarried young females who have small breast. Swiss-roll operation is superior in maintaining the shape and symmetry of breast. No major complication was found in our series except seroma formation in 10 patients. PMID- 20364748 TI - Awareness of women towards an emerging threat. AB - BACKGROUND: The human immunodeficiency virus/Acquired immunodeficiency syndrome (HIV/AIDS) pandemic continues it deadly assault in different parts of the world. Over 20 million people have died since the first case of AIDS was identified in 1981. Despite increased spending on HIV/AIDS programmes and improved responses by many governments, current global efforts remain entirely inadequate for an epidemic that is continuing to spiral out of control. The objective of this study was to determine the level of awareness about HIV and AIDS among women attending the obstetrics and gynaecology clinic. METHODS: This Descriptive study was conducted in the Obstetric & Gynaecology clinic at LUMHS, Hyderabad Pakistan from 5th July 2007 to 3rd Dec 2007. A total of 178 women attending obstetric and gynaecology clinic of age 20-55 years were selected randomly. Information was collected by pre-designed questionnaire to assess the level of awareness about HIV/AIDS. RESULTS: About 83.7% women had heard about HIV/AIDS and only 44.3% correctly stated the difference in HIV/AIDS. Only 41.5% of respondents knew how would infected person present, and 55.6% respondents knew that it is transmitted through close sexual relationship, while less than 50% correctly answered about mode of transmission through coughing, sneezing, hand shaking, kissing and ear/nose piercing. Among the respondents, 52.2% correctly answered that screening of blood before transmission can prevent HIV and only 38.2% respondents knew that HIV is preventable disease. CONCLUSION: Women demonstrated lack of knowledge regarding HIV/AIDS and there are considerable misconceptions and myths in certain aspects which need to be clarified through educating women. PMID- 20364749 TI - Diagnostic significance of adenosine deaminase in pleural tuberculosis. AB - BACKGROUND: Tuberculosis (TB) is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Analysis of adenosine deaminase (ADA) activity is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in cases of Pleural TB (pTB). METHODS: Fifty male and fifty female patients presenting with tuberculous pleural effusion was included in the study. The patients were taken from the medical ward of Sir Ganga Ram Hospital between September 2001 and September 2002. Activity of Adenosine Deaminase (ADA) was estimated by the technique of Sodium dodecyl sulphate electrophoresis (SDS-EF) using 10% polyacrylamide gel. RESULTS: Mean age of males was 45.72 +/- 19.22 years and of female was 43.74 +/- 16.09 years. Mean protein level was 3.39 +/- 0.24 g/dl in males, and it was 3.02 +/- 0.26 g/dl in females. Mean specific gravity both in males and females was 1.020 +/- 0.01. The results show an increased level of enzyme ADA in patients as compared to normal subjects. CONCLUSION: Estimation of ADA activity may provide basis for rapid and efficient diagnosis of pleural TB in different clinical settings. However study should be extended to larger number of patients to reach a better conclusion. PMID- 20364750 TI - Placing epicardial pacing wires in isolated coronary artery bypass graft surgery- a procedure routinely done but rarely beneficial. AB - BACKGROUND: After Coronary Artery Bypass Graft (CABG) surgery, temporary epicardial pacing wires are placed on heart to meet unforeseen complications like bradyarrhythmias or asystoles. This step needs additional time, resources and has potential to cause complication. Even having less complications, is this additional step in elective CABG surgery necessary? Some important predictive factors in patients who require this pacing wire placement have to be isolated. The objective of the study was to avoid this step if not required especially in elective CABG surgery. METHODS: This prospective observational study involved 1047 consecutive patients undergoing CABG at our institution from May 2006 to April 2008. Patient who did not receive pacing wire (230), Preoperative pacemaker (2), CABG with valvular surgery (10), CABG with Ischemic VSD or MR surgery (3), off-pump CABG (21), or incomplete follow-up (11) were excluded from the study. Patients who received pacing wire (770) were divided in two groups. Group A, consisted of patients who did not require pacing postoperatively 748 (97.1%), and Group B, who required pacing postoperatively 22 (2.9%). Both groups were compared in demographic, preoperative, per-operative and postoperative variables. The incidence of pacing during the postoperative period was recorded. Predictors for postoperative pacing were determined using medical records and the AFIC/NIHD cardiac surgery database. RESULTS: In the postoperative period, 22 of 770 patients (2.9%) required pacing. Analysis identified age (p = 0.02), preoperative arrhythmia, especially Bundle Branch Block (p = 0.000), pacing utilized at separation from bypass (p = 0.000) and use of antiarrhythmics on leaving the operating room (p = 0.015) as predictors of the need for postoperative pacing. Diabetes, considered one of the major factor requiring pacing was not significant in our study (p = 0.379). Preoperative arrhythmias, pacing utilized to separate from bypass and use of antiarrhythmics on leaving the operating room were found to be three most significant risk factors. If the patients with any of these three risk factors are excluded, only 1.11% (8/716) of them would have required pacing. CONCLUSIONS: Procedure of routine use of temporary epicardial pacing after elective CABG surgery has negligible role, rather has additional cost and potential of rare complications. Diabetes is not a risk factor for post operative pacing. PMID- 20364751 TI - Audit of appropriateness and outcome of computed tomography brain scanning for headaches in paediatric age group. AB - BACKGROUND: Headache is a common complaint in children. With the proliferation of brain imaging centers and the increasing patient demand for CT or MRI studies, brain imaging has become widely used to evaluate headache and exclude malignant lesion. The objectives of this descriptive study were to assess the appropriateness and outcomes of computed tomography brain scanning for headaches in paediatric age group. This study was conducted at the Radiology Department Hayatabad Medical Complex, Peshawar over a period of 1 year July 2008-July 2009. METHODS: Both genders between the ages of 4-18 years included in the study presenting with headache either isolated or common/classic migraine were included in this study. These variants of headache were allocated an appropriateness rating of 2 for CT scan by the American College of Radiology Appropriateness Criteria (ACRAC) for children with headaches. RESULTS: Out of the 100 patients only 4% patients showed abnormal findings on CT scan while the remaining 96% of the scans were absolutely normal. The four patients with abnormal findings all had sinusitis no notorious lesions. CONCLUSION: This audit suggests that a proportion of the computed tomography studies performed for children with isolated headaches or common/classic migraine may have been inappropriate. The development of a local guideline for imaging referral is indicated. PMID- 20364752 TI - Gestational trophoblastic disease: experience at Nawabshah Hospital. AB - BACKGROUND: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant potential of this disease is higher in South East Asia in comparison to western countries. Objectives of study were to determine the frequency, clinical presentation and management outcomes of GTD. This retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007. METHODS: The case records of all the gestational trophoblastic cases during study period were analysed regarding their history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. RESULTS: There were a total of 1056 Obstetric admissions during the study period, which included 30 cases of trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%) patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29 (96.7%) fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain. CONCLUSION: Frequency of GTD was higher compared to national and international studies. The disease was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the commonest type of trophoblastic disease in these patients. Most common presenting complaint was bleeding per vagina followed by pain in lower abdomen. PMID- 20364753 TI - Variable response to inhaled nitric oxide in postoperative patients of mitral stenosis with pulmonary hypertension. AB - BACKGROUND: This study was carried out to determine the vasodilator response of inhaled nitric oxide in patients with pulmonary hypertension (PH) after valve replacement surgery for mitral valve disease. METHOD: This Quesi experimental study was carried out at the intensive care unit of Armed Forces Institute of Cardiology (AFIC) in collaboration with Department of Physiology, Army Medical College, Rawalpindi from March 2004 to February 2006. Thirty patients with systolic Pulmonary Artery Pressure (PAP) > 50 mmHg on pre-operative echocardiography were inducted. Swan Ganz catheter was inserted to record baseline pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP), while cardiac output (CO) was recorded through lithium dilution method. Pulmonary Vascular Resistance (PVR) was calculated with the help of a formula. Inhaled nitric oxide (iNO) was administered after the surgery and the same parameters were recorded again after one hour. RESULTS: The majority of patients were females (73%), while males were only 27%. Out of 30, 21 had isolated mitral stenosis and 9 had mixed mitral and aortic valve disease. 22 patients responded significantly to iNO therapy with > or = 40.0% reduction in their baseline PVR while 8 patients showed insignificant improvement in their PVR (663 +/- 233 dynes.sec.cm(-5) to 605 +/- 222 dynes.sec.cm(-5)). CONCLUSION: Significant improvement in pulmonary vascular resistance in the responders and maintenance of high pressures despite iNO therapy in non-responders indicate that apart from some abnormality in nitric oxide pathway, some other factors may be a contributing in the causation of PH secondary to mitral stenosis in adults, which warrant further studies. PMID- 20364754 TI - Management of diabetic foot by natural honey. AB - BACKGROUND: Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. Research has also indicated that honey may possess anti-inflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. The objective of the study was to find out the results of topical wound dressings in diabetic wounds with natural honey. METHODS: The study was conducted at department of Orthopaedics, Unit-1, Liaquat University of Medical and Health Sciences, Jamshoro from July 2006 to June 2007. Study design was experimental. The inclusion criteria were patients of either gender with any age group having diabetic foot Wagner type I, II, III and II. The exclusion criteria were patients not willing for studies and who needed urgent amputation due to deteriorating illness. Initially all wounds were washed thoroughly and necrotic tissues removed and dressings with honey were applied and continued up to healing of wounds. RESULTS: Total number of patients was 12 (14 feet). There were 8 males (66.67%) and 4 females (33.33%), 2 cases (16.67%) were presented with bilateral diabetic feet. The age range was 35 to 65 years (46 +/- 9.07 years). Amputations of big toe in 3 patients (25%), second and third toe ray in 2 patients (16.67%) and of fourth and fifth toes at the level of metatarsophalengeal joints were done in 3 patients (25%). One patient (8.33%) had below knee amputation. CONCLUSION: In our study we observed excellent results in treating diabetic wounds with dressings soaked with natural honey. The disability of diabetic foot patients was minimized by decreasing the rate of leg or foot amputations and thus enhancing the quality and productivity of individual life. PMID- 20364755 TI - In vitro activity of linezolid against clinical isolates of methicillin resistant Staphylococcus. AB - BACKGROUND: Staphylococcus is responsible for a variety of medical problems, including skin and soft-tissue infections (SSTIs), surgical site infections (SSIs), endocarditis and hospital acquired bacteraemia. Methicillin resistance in staphylococcus has become a global problem limiting the treatment modalities to a large extent. METHODS: The aim of this study was to evaluate the in vitro activity of linezolid and other antibiotics against clinical isolates of methicillin resistant staphylococcus (n = 163); including 105 methicillin resistant Staphylococcus aureus and 58 methicillin resistant coagulase negative staphylococci. Antibiogram of these isolates was determined by the Kirby-Bauer disc diffusion method and minimum inhibitory concentration of linezolid was determined by standard agar dilution method. RESULTS: Overall methicillin resistant S. aureus showed high multi-drug resistance. ATCC 25923 Staphylococcus aureus and ATCC 29213 Staphylococcus aureus were used as the standard control strains. MIC90 of linezolid was comparable for methicillin resistant coagulase negative staphylococci and methicillin resistant S. Aureus (4.0 mg/L); however at MIC50 linezolid was two fold more active against methicillin resistant coagulase negative staphylococci (1 mg/L) than methicillin resistant S. aureus (2 mg/L). CONCLUSION: It is concluded that linezolid has excellent activity against methicillin resistant staphylococci including multidrug resistant strains. PMID- 20364756 TI - The impact of hyperglycaemia on morbidity and mortality of acute coronary syndromes and acute myocardial infarction. AB - BACKGROUND: Though diabetes and hyperglycaemia are well known risk factors for morbidity and mortality associated with Coronary Heart Disease, there are no studies published from Pakistan on the impact of non-diabetic hyperglycaemia on these indices. The present study was undertaken to fill the gap in knowledge related to this aspect of hyperglycaemia in Pakistani patients. METHODS: We studied 166 patients admitted to our coronary care unit from May 2008 to March 2009 with acute coronary syndrome and acute myocardial infarction. The patients were divided into three groups (a) Diabetic group (b) Impaired glucose group and (c) Normal glucose group according to the American Diabetic Association criteria. RESULTS: It was observed that with increasing level of hyperglycaemia there was an increase in the mortality, with a p-value of 0.058. Hyperglycaemia was also associated with impaired left ventricular function and clinical evidence of left ventricular failure. Insulin therapy was under utilized and may have contributed to increased morbidity and mortality. PMID- 20364757 TI - Yield of Abrams needle pleural biopsy in exudative pleural effusion. AB - BACKGROUND: Pleural effusion is the abnormal collection of fluid in the pleural space resulting from excessive fluid production or decreased absorption and it is one of the most common clinical conditions that we come across in pulmonology clinics and in hospitals. The objective of prospective study was to evaluate the diagnostic role of Abrams Needle Biopsy in Exudative Pleural Effusion. METHODS: The study was performed at the Department of Pulmonology, Ayub Teaching Hospital, Abbottabad over a period of 1 year, i.e., January 2008 to December 2008. Sixty three patients of either sex and all ages with exudative pleural effusion, on whom Abrams Needle Biopsy was performed were included in the study. Minimum of four specimens from each patient were taken and histopathology done. RESULTS: Out of 63 patients, histopathology revealed the cause in 60 (95%) cases. Tuberculosis, malignancy and rheumatoid pleurisy were confirmed in 34, 24, and 2 cases respectively. Specimens of3 patients did not reveal any result and showed non-specific inflammation and were further investigated accordingly. CONCLUSION: The diagnostic yield of Biopsy was 95%. Pleural biopsy is still a reliable and valuable investigation in diagnosing pleural effusion, provided that adequate pleural specimen is taken. PMID- 20364758 TI - Screening of 110 cirrhotic patients for hepatitis B and C at Saidu Teaching Hospital Saidu Sharif Swat. AB - BACKGROUND: Cirrhosis liver is amongst the commonest clinical conditions in Pakistan. Besides other causes, it is mostly related to previous viral infection, in this part of the world. The main objective of this study was to find the frequency of HBsAg and anti HCV in cirrhotic patients of Swat district. METHODS: This Prospective Study was conducted in the Medical unit of Saidu Teaching Hospital, Saidu Sharif from January 2006 to December 2006. One hundred and ten Cirrhotic Patients, 62 Male and 48 Female aged from 14 to 75 years were included in this study. Sera were tested by 3rd generation Elisa method. RESULTS: Fifty nine out of 110 (53.6%) patients were positive for anti HCV antibodies. Twenty four (21.81%) Patients were positive for HBsAg. Eleven (10%) patients were positive for both HBsAg and anti HCV anti bodies. Sixteen (14.54%) were negative for both sero maker of hepatitis B and C. CONCLUSION: It is evident from this study that Hepatitis C, is a leading cause of cirrhosis in District Swat followed by HBV. Both the viruses account for at least three fourths of the total Cirrhotic. PMID- 20364759 TI - Frequency and management outcome of pneumothorax patients. AB - BACKGROUND: Primary spontaneous pneumothorax is a common clinical problem and its incidence is thought to be increasing. This study was conducted to see the frequency, aetiology, presentation and management outcomes of pneumothorax in patients presenting at Pulmonology unit, Ayub Teaching Hospital, Abbottabad, Pakistan. METHODS: Pneumothorax patients reporting at the Pulmonology unit of Ayub Teaching Hospital, Abbottabad from 2002 to December 2008 were included in the study. Patients of all ages were included. They were admitted and followed up to the full recovery. RESULTS: A total of 195 pneumothorax patients reported during this period. Majority of the patients were diagnosed to have pneumothorax due to pulmonary tuberculosis making about 36.92% of the total cases. Second most common cause was primary spontaneous pneumothorax (21.53%). COPD were also sizeable at 8.71%. Other causes included Bacterial infections, Asthma, iatrogenic, interstitial lung disease, bronchiectasis and Trauma. CONCLUSION: It was concluded from this study that pulmonary tuberculosis is the commonest cause of pneumothorax in our setup. PMID- 20364760 TI - Prevalence of necrotizing fasciitis during Ramadan and Hajj 1427-H. AB - BACKGROUND: Necrotizing Fasciitis is a rare progressive disease which results in significant rate of mortality and morbidity if there is any delay in diagnosis and treatment. Objectives of this Prospective observational study were to share our experience of dealing necrotizing fasciitis in terms of different presentations, diagnosis, treatment and outcome during Ramadan and Hajj. It was conducted in the Department of General Surgery, Al-Noor Specialist Hospital, Holly Makkah, KSA during Ramadan and Hajj period from 1-8-1427 to 30-1-1428. METHODS: Total 35 patients > 12 years of age, irrespective of the gender belonging to different nationalities admitted to Al-Noor specialist hospital, Makkah, KSA were included in this study to evaluate the different causative factors, presentations, response to medical/surgical treatment and outcome. RESULTS: Total 35 patients with male to female ratio of 6:1 were admitted during Ramadan and Hajj period from 1-8-1427 to 30-1-1428 (six months) with the features of necrotizing Fasciitis. Out of these 35 patients, 23 (65.7%) were Hajji and 12 (34.28%) were residents (Both Saudi and non Saudi) with a ratio of 2:1. Major co morbid factors were old age, diabetes mellitus, hypertension and renal failure. Among systemic manifestations, 4 (11.42%) developed septic shock and admitted to ICU, 4 (11.42%) needed ventilator support for respiratory failure, and 5 (14.28%) patients developed Myocardial infarction. After resuscitation, 33 patients under went aggressive surgical debridement and two patients died before surgery. Microbiology revealed, 15 (42.85%) Streptococcus Group-A infection, 13 (8.51%) Polymicrobial and 4 (11.42%) MRSA. Diagnosis was conformed by histopathology. Mortality rate was 11.5%. CONCLUSION: Better outcome in necrotizing fasciitis depends upon early presentation, prompt diagnosis and aggressive surgical debridement. There was strong correlation between severity of necrotizing fasciitis and co morbid factors, general condition at presentation, systemic toxicity and raised WBC count. PMID- 20364761 TI - Dose related shifts in the developmental progress of chick embryos exposed to mobile phone induced electromagnetic fields. AB - BACKGROUND: The possible adverse effects of Electromagnetic Fields (EMFs) emitted from mobile phones present a major public concern today. Some studies indicate EMFs effects on genes, free radical production, immunological and carcinogenic effects. On the other hand there are studies which do not support the hypothesis of any biological impacts of EMFs. This study was designed to observe the effects of mobile phone induced EMFs on survival and general growth and development of chick embryo, investigating dose-response relationship if any. METHODS: This was an experimental study in which developing chick embryos were exposed to different doses of mobile phone induced EMFs. For this purpose a mobile phone was placed in the incubator in the centre of fertilised eggs in silent ringing mode and was 'rung' upon from any other line or cell phone. After incubation for 10 or 15 days the eggs were opened and the developmental mile-stones of the surviving embryos were compared with the non exposed subgroup. RESULTS: EMFs exposure significantly decreased the survivability of the chick embryos. The lower doses of EMFs caused growth retardation. However, this effect of growth retardation reallocated to partial growth enhancement on increasing the dose of EMFs and shifted over to definite growth enhancement on further raising the dose. CONCLUSION: There is an adverse effect of EMFs exposure on embryo survivability. Chick embryos developmental process is influenced by EMFs. However, these effects are variable depending upon the dose of EMFs exposure. PMID- 20364762 TI - Palliative surgery for intestinal obstruction due to recurrent ovarian cancer. AB - BACKGROUND: Intestinal Obstruction is a frequent complication after operation for Ovarian Cancer. This study was done to see the outcome of palliative surgery for Intestinal Obstruction due to recurrent ovarian Cancer. METHODS: We retrospectively evaluated the records of all the patients who presented with intestinal obstruction after operations for Ovarian Cancer in all the three Surgical Units of Ayub Teaching Hospital Abbottabad from March 1998 to April, 2009. Demographic data, type of management, morbidity, mortality, hospital stay, surgical procedure, symptomatic relief, return of bowel function and outcome were analyzed. RESULTS: There were 56 patients with symptoms of partial or complete intestinal obstruction. Conservative treatment was successful in 22 (39%) patients. Laparotomy was done in 30 (53.5%) patients. The cause of intestinal obstruction was adhesions 8 (26.6%), local recurrence 10 (33.3%) and diffuse carcinomatosis in 12 (40%) patients. Palliative surgery was done in 20 (66.6%) patients while 8 (26.6%) had adhesionolysis only. 9 (30%) patients had resection and anastomosis, 7 (23.3%) had bypass surgery, 3 (10%) had colostomy and one (3%) had Hartmann procedure. Postoperative complications occurred in 26 (86.6%) patients. 12 (40 %) patients died after surgery. Mean hospital stay was 18 (9-42) days. Palliative surgery was successful in 8 (26.65%). CONCLUSIONS: Majority of patients with Intestinal obstruction after operation for Ovarian Cancer can be managed conservatively. Palliative surgery is associated with high mortality and morbidity but it should be done in patients not responding to conservative measures. PMID- 20364763 TI - Anxiety and depression in burn patients. AB - BACKGROUND: The psychological aspects of burn injury have been researched in different parts of world producing different outcomes. Therefore objective of this research is to determine the frequency of Anxiety and Depression in burn patients. To assess the socio-demographic distribution of patients developing Anxiety and Depression and to determine the effects of burn related factors on development of Anxiety and Depression. METHODS: A Case series was conducted at the Department of Burn, Pakistan Ordinance Factory Hospital, Wah Cantt. for a duration of 12 months commencing from June 2007 and concluded in May 2008. The study population comprised of hospitalized patients with 1% to 50%, selected through non probable sampling technique who were assessed for Anxiety and Depression on fifteen day after burn injury. Testing protocol comprised of questionnaire having socio-demographic variables and burn related variables. Beck Depression Inventory and Beck Anxiety Inventory was applied to evaluate Anxiety and Depression in Burn patients. Descriptive statistics like mean with Standard Deviation was calculated for age. Frequencies along with percentages were calculated for socio-demographic variables. The frequencies and proportions were also calculated for presence and extent of severity of depression and anxiety in burn patients. RESULTS: Fifty patients were included in the study, thirty patients (60%) were male and 20 (40%) were females. The mean age of participants was 33.64 +/- 19 years. Majority of participants, 38 (76%) had sustained burn injury up to 25%. Flame was found to be most common agent of burn injuries affecting 19 (38%) patients. Depression was seen amongst 29 (58%) patients. Thirteen (26 %) patients had mild, 7 (14%) had moderate and 9 (18%) had severe Depressive symptoms. Anxiety was seen among 41 (82%) patients, thirteen (26%) patients had mild, 11 (22%) had moderate and 17 (34%) had severe Anxiety symptoms. CONCLUSION: Anxiety was present in 41 (82%) and Depression was present in 29 (58%) patients following burn injury. This study highlights the importance of the simultaneous evaluation and management of Anxiety and Depression in burn injured patients. PMID- 20364764 TI - Modelling survival data of thalassaemia patients in Pakistan. AB - BACKGROUND: Fatimid Foundation with its centers serves as a charitable organization for millions of blood disease carriers in Pakistan. This retrospective survival study is an analysis of the Thalassaemia patients registered in Multan centre who are followed up to nine years to assess the gender risk of death. METHODS: Data on 120 patients of Thalassaemia during 1994 2002 was analyzed. The standard Kaplan-Meier and Nelson-Aalen procedures were used to compare the survival function of the male and female patients of Thalassaemia. The statistical significance was also assessed using log rank test. The Cox Proportional Hazards (PH) model using a forward selection procedure was used to identify the potential factors associated with the increase risk of death. RESULTS: By ignoring the censoring, the average survival time of males and females were calculated to be 1308.1 and 1574.7 days respectively. The average hazard rate for the female group was 0.00033 and for the male group it was 0.00061. The median survival time was estimated from the Kaplan-Meier survival curves (Males: 1400 days, Females: 1785 days). Under the censoring mechanism, the mean survival time for males was calculated to be 1465.82 days with standard error of 146 days, where as for females it was calculated to be 1855.26 with standard error of 151.82 days. When considering death as event of interest Under the Cox modelling approach, we found a male patient of Thalassaemia was 1.484 times more likely to die when compared to his female counterpart. When considering the iron over load as the event of interest, we found a male patient of Thalassaemia was 1.753 fold more likely to reach excessive Haemochromatosis level compared to female patient. CONCLUSION: The analysis reinforces that female group prognosis is better than the male group. Further, our analysis of real survival data set shows that the high status of Haemochromatosis level is associated with the increased risk of death in patients with Thalassaemia with other possible confounders. PMID- 20364765 TI - Squamous cell carcinoma of the conjunctiva: analysis of fifteen cases. AB - BACKGROUND: To document various clinical presentations and management options of conjunctival squamous cell carcinoma (CSCC) in patients attending ophthalmic out patients department (OPD) of a tertiary care centre. This case series was carried out in the Department of Ophthalmology Civil Hospital and, Dow University of Health Sciences, Karachi and were reviewed from June 2004 to December 2007. METHODS: Socio-demographic data and clinical features of patients with biopsy proven conjunctival squamous cell carcinoma were recorded and analysed. All patients underwent complete ophthalmic examination by a fellow ophthalmologist and clinical findings were recorded on a prescribed Performa. Data was analysed in terms of frequency, means and median by SPSS for windows V.15. RESULTS: Seventy-two percent of the patients were male and 28% were female, more than 80% of patients were in the age group of seventy years and above. Eighteen percent of patients developed intraocular invasion and the eyes had to be enucleated. CONCLUSION: CSCC occurs in sun damaged ocular surface usually at limbus, elderly men are more commonly involve, recurrence is a feature of disease and high risk in older individual. In our treatment we used various therapies, excision with clear margin, topical mitomycin C adjunctive cryotherapy and amniotic graft. PMID- 20364766 TI - Histological effects of Eugenia jambolana seed extract on liver of adult albino rats. AB - BACKGROUND: The therapeutic value of Eugenia jambolana, commonly known as 'Jamun' in Hindi, has been recognized in different system of traditional medicine for the treatment of various conditions. Its seeds are used for the treatment of diabetes mellitus and hyperlipedemia by reducing the lipid levels in the body; this action is presumed to be due to blocking the action of enzyme 3-hydroxyl methyl glutaryl (HMG-CoA reductase in the liver. Herbal drugs are getting into use with the notion that these are relatively harmless; the practice has shown that many of them also have toxic effects. Since hardly any work is available on the toxic aspect of Eugenia Jamblana, the present study was planed to see the effect-of ethanolic extract of Eugenia Jamblana on liver using albino rats as an experimental model. METHODS: The animals were divided into three groups A, B and C. Group A served as a control and received only distilled water comparable to the experimental animals calculated according to their body weight, where as B and C served as experimental groups. 100 and 200 mg of ethanolic extract of Eugenia Jamblana was dissolved in one ml of distilled water each and was given orally for 30 days/kg body weight. RESULTS: liver enzyme ALT and gamma GT were significantly raised when compared to the control group, p-value being < 0.05. Histological studies showed ballooning degeneration of hepatocytes, focal areas of hepatocytes necrosis with lymphocytic infiltration, providing supportive evidence for biochemical findings indicative of functional derangement. The effect of the extract was not dose dependent. Statistical analysis using ANOVA and chi-square showed statistically significant difference when the values from experimental animals were compared with those from the control, indicating that the ethanolic extract of Eugenia Jamblana seed possesses hepatotoxic effect. CONCLUSION: The ethanolic extract of Eugenia jambolana seed extract is toxic to liver as evident by derangement in liver enzyme levels and disturbed liver histology. PMID- 20364767 TI - Management of thoracic trauma: experience at Ayub Teaching Hospital, Abbottabad. AB - BACKGROUND: The incidence of thoracic trauma has rapidly increased in this century of high speed vehicles, violence and various other disasters. It has been observed that chest intubation was required in more than 75% of patients. METHODS: This prospective study was performed in cardiothoracic surgery unit of Ayub Teaching Hospital Abbottabad from Jun 2007 to Dec 2007. A total of 114 consecutive patients with chest trauma were included in the study, their patterns of injuries classified, treatment strategies and outcome were recorded on a proforma. RESULTS: Out of 114 patients with chest trauma, 76 (66.65%) were having penetrating and 38 (33.33%) had blunt trauma. Haemothorax was detected in 67 (58.77%), Pneumothorax in 23 (20.17%), rib fracture in 11 (15.02%) and diaphragmatic injuries in 4 (3.5%) cases. Overall complication rate was 14%. Wound infection was present in 8 (7.01%) and empyema in 4 (3.5%). Mortality was 2.6%. CONCLUSION: Penetrating chest injuries were more common than blunt injuries and chest intubation with resuscitation was adequate in most of the patients. PMID- 20364768 TI - Analysis of homicidal deaths in district DI Khan: an autopsy study. AB - BACKGROUND: One of the oldest crimes in human civilization is homicide which started from murder of Abel by the hands of Cane. With the passage of time manner of homicide have been changing. Study of pattern of homicide in any civil society is the first step towards development of intervention to reduce the impact of homicidal crimes. This study was conducted at the department of forensic medicine and toxicology Gomal Medical College DI Khan to know the pattern of the homicides, taking it as the first step in the prevention of crime. METHODS: The present study was conducted over two years 2007-08. The data collected includes all reported unnatural deaths from the urban and rural areas of district on which autopsies were conducted in the district headquarter teaching hospital DI Khan and department of Forensic Medicine and Toxicology, Gomal Medical College DL Khan. RESULTS: Homicidal deaths constituted 259/341 (76%) of all autopsies. Out of these homicides 59.07% were caused by the firearm. The most common firearm weapons were high velocity rifled weapons (AK-47, rifles and pistols). A total of 304 injuries were found in various body regions giving an average of about two injuries per victim/person. The head, neck and face sustained the highest numbers of injuries 100, (32.90%) followed by chest 91 (29.93%) and abdomen 47 (15.4%); the extremities, buttock and genitalia together sustained 65 (21.38 %) injuries. A part from firearm injuries unfortunately in our this study the second highest cause of homicidal deaths was bomb blasts injuries either due to suicide bombers or remote control bombs. The numbers of deaths due to blast injuries were 82 for the year 2007/08 out of total homicidal deaths and percentage was 32.66%. CONCLUSION: The vast majority of homicidal deaths in this area are caused by firearms like other big cities of the province like Peshawar, which bring up issues related to possession of firearms and change in cultural attitude towards the use of firearm, if a decrease in firearm related homicides is desired. PMID- 20364769 TI - Study of blood lipids, cortisol and haemodynamic variations under stress in male adults. AB - BACKGROUND: Increased cholesterol in blood plays the role in atherosclerosis formation. It is observed that stress increases cholesterol level. Most of previous studies were conducted on biological risk factors like blood lipids under stress in middle aged persons who remained under investigations for heart problems. OBJECTIVE: The study was conducted to evaluate the changes in blood lipids and blood cortisol along with sympatheo-adnergic responses determined by selected haemodynamic parameters during psychological stress. METHODS: Male participants (n = 114) were randomly selected. They were examined two times, for stress task of viva-voce (degree examination) and during non-stress period. Final selection of participants was depending on stress assessment and their well being. RESULTS: Cortisol, systolic and diastolic blood pressures (SBP and DBP) and heart rate (HR) were significantly increased during stress period with p < 0.001 for each parameter. But different blood lipids levels (TC, LDL-C, HDL-C and TG) were detected with different significant levels. The correlations of changed lipids with raised findings of haemodynamics and cortisol were also evaluated. CONCLUSION: Further studies in our population are needed to evaluate the relation of changes in various biological risk factors including IL-9 and sympatho adernergic activities with stress factors related to our social/ environmental problems, especially genetically based psychological factors. PMID- 20364770 TI - Laparoscopic cholecystectomy for left sided gall bladder: an unusual case. AB - We report a rare case of a female patient with situs inversus totalis. She developed cholelithiasis which was diagnosed on abdominal ultrasound and she underwent laparoscopic cholecystectomy for the left sided gall bladder. The literature on this subject is reviewed. We want to highlight the important aspects of the management in such rare scenario. PMID- 20364771 TI - Dedifferentiated chordoma with a sarcomatous component: an overlooked diagnosis. AB - A 60 year old male presented with unremitting complaints of acute urinary retention and constipation. Computerized Tomography of the abdomen and pelvis confirmed a sacral mass. The biopsy diagnosed dedifferentiated sacral chordoma; an extremely rare entity, seldom reported and frequently misdiagnosed. We present a unique case report after an extensive review of retrospective literature on dedifferentiated chordomas. PMID- 20364772 TI - Well leg compartment syndrome: the debit side of hemilithotomy position. AB - We describe a case of well leg compartment syndrome following unilateral lithotomy position in a patient undergoing contralateral antegrade intramedullary femoral nailing. Following two-incision four compartment fasciotomy, the patient recovered with no residual defects. We dissuade use of the hemilithotomy position for antegrade femoral nailing procedures in favour of another previously described position, because this predisposes patients to position-associated complications without offering any substantial advantage. PMID- 20364773 TI - Oral mucocele (mucous extravasation cyst). PMID- 20364776 TI - Getting services back on track. Interview by Sophie Blakemore. PMID- 20364777 TI - 200,000 sterling pounds in damages for paramedic injured while carrying equipment bag. PMID- 20364778 TI - Therapeutic hypothermia. PMID- 20364779 TI - High impact interventions to control infection. AB - High impact interventions can be undertaken to improve, and to monitor the effectiveness of, infection control procedures in emergency departments (EDs). Any member of a clinical team can lead on implementing these interventions, although motivating colleagues to take part is sometimes difficult. This article discusses non-compliance with infection control procedures and examines how ED staff can use high impact interventions. PMID- 20364780 TI - Disaster relief: helping the survivors of the Haiti earthquake. AB - Haiti shares the island of Hispaniola with the Dominican Republic in the Caribbean Sea. On January 12, the country was the site of an earthquake, measuring 7.0 on the Richter scale, with the epicentre about 16 miles west of the capital, Port-au-Prince. The earthquake caused widespread loss of life and damage, and many organisations responded to appeals from the Haitian people for humanitarian aid. Among these was the UK-based charity Merlin. Calderdale and Huddersfield NHS Foundation Trust emergency nurse Deb Lau works for Merlin and here she describes what happened when she travelled to Haiti to help provide medical relief. PMID- 20364781 TI - Views of relatives, carers and staff on end of life care pathways. AB - More people die in hospital than at home (Department of Health (DH) 2008). Yet, many people do not want to die in hospital, which can be an inappropriate environment for end of life care. The government's end of life care strategy (DH 2008) and the NHS (2009) end of life care programme (EOLCP) state that people should be able to choose where they die. This article reports on the findings of a study on end of life care of decisions by patients, relatives and care professionals, and their perceptions of care pathways in the last 48 hours of life. It also highlights the challenges that must be overcome in acute and community settings for the aims of the EOLCP to be met. PMID- 20364782 TI - Assessing the neurological status of patients with head injuries. AB - The aim of this article is to inform staff who are new to emergency care settings how to use the Glasgow Coma Scale (GCS) when managing patients with head injuries. It may also be useful as a refresher for experienced staff and a helpful teaching tool. It emphasises the need for continual, standardised assessment of neurological status and emphasises how the GCS is seen as best practice nationally and internationally. PMID- 20364783 TI - Early management of children with minor head injuries. AB - In the UK, about 260,000 children with head injuries attend emergency departments each year (National Institute for Health and Clinical Excellence (NICE) 2007, Scottish Intercollegiate Guidelines Network (SIGN) 2009). About 90 per cent of these injuries are minor and can be managed without admission to hospital (Swann and Teasdale 1999). Clinical guidelines for early management of head injury have recently been published by NICE in England and Wales, and by SIGN in Scotland, to standardise management across the UK. This article discusses the role of emergency nurses in implementing these guidelines. PMID- 20364784 TI - Keeping a dream alive. PMID- 20364785 TI - Exploring the role of RNs in family practice residency training programs. AB - The authors developed a survey as part of a study to explore the role of nurses employed in Canadian family practice residency training programs, which provide physicians with two years of additional training after they have completed undergraduate medical education. Licensed practical nurses, registered nurses and nurse practitioners employed at residency traininig program sites have a unique opportunity to educate new physician about nursing scopes of practice and about how to work effectively with nurses. A total of 127 nurses, including 94 RNs, from 41 program sites across Canada completed the survey. In this article, the authors present the finding specific to this RN group. RN respondents reported performing a wide range of nursing and non nursing activities, and only 61 per cent indicated that they felt they worked to full scope. That so many RN respondents were performing below their scope of practice may be the result of employer and organizational policies or a lack of understanding and awareness of scope of practice. The authors propose that family practice residency training programs adopt a standardized approach to the role of RNs. PMID- 20364786 TI - An invitation from CPHA. PMID- 20364787 TI - Reaching out to people who hoard. PMID- 20364788 TI - Driving change in public health. Interview by Tara Tosh Kennedy. PMID- 20364789 TI - Has our diversity become a stumbling block? PMID- 20364790 TI - Genetic analysis of modifiers for the hooded phenotype in the rat. AB - The hooded phenotype is one of the coat color phenotype seen peculiarly in the rat. The hooded locus showing autosomal recessive inheritance is mapped to chromosome (Chr) 14 and that the hooded phenotype receives modification by hooded modifier gene showing the linkage to the hooded locus. However, a gene responsible for either the hooded or hooded-modifier gene is not yet identified. To clarify genetic control of hooded phenotype, we carried out genetic linkage studies using BN and LEA rats. For determination of phenotypic variation, we measured ratio of pigmented coat area in parental and their F1 and F2 rats. We, then, conducted a genome-wide scan on 152 F2 rats for linkage with ratio of pigmented coat area for the dorsal, ventral, and total regions. A major quantitative trait locus (QTL), D14Got40, showing highly significant linkage contributing 70-90% of the variance for hooded phenotype was detected on Chr 14, which may be correspondent to the hooded locus. In addition, another QTL, D17Rat2, showing highly significant linkage was also detected on Chr 17 in dorsal region phenotype as well as a QTL showing suggestive linkage on Chr15 in ventral region phenotype. We, further, investigated a genome-wide scan for epistatic interactions and detected significant interactions between D14Got40 and D20Mit1, and between D14Got40 and D17Rat2 in the dorsal region phenotype. These results suggest that a major QTL in Chr 14, which is possibly correspondent to the hooded locus, mainly regulates the hooded phenotype with some modifier loci, two of which show epistatic interactions with the hooded locus. PMID- 20364791 TI - Changes in plasma gonadotropins, inhibin and testosterone concentrations and testicular gonadotropin receptor mRNA expression during testicular active, regressive and recrudescent phase in the captive Japanese black bear (Ursus thibetanus japonicus). AB - Male Japanese black bears (Ursus thibetanus japonicus) have an explicit reproductive cycle. The objective of this study was to clarify the variation of plasma testosterone, FSH, inhibin, LH levels and testicular gonadotropin receptor mRNA expression of male bears associated with their testicular activity. Notably, this study investigated peripheral FSH concentration and localization of gonadotropin receptor mRNAs for the first time in male bears. Blood and testicular tissue samples were taken from captive, mature, male Japanese black bears during testicular active, regressive and recrudescent phases. Plasma hormone concentrations were measured by immunoassays, and gonadotropin receptor mRNA expression in the testis was investigated by in situ hybridization technique and also by real-time PCR. There were significant variations in plasma testosterone and inhibin concentrations. Changes in FSH concentration preceded these hormones with a similar tendency. Hormones started to increase during denning, and achieved the highest values at the end of the recrudescent phase for FSH and in the active phase for testosterone and inhibin. These changes in hormone concentrations were accompanied by testicular growth. In situ hybridization analysis revealed that FSH and LH receptor mRNA was possibly expressed in Sertoli cells and Leydig cells, respectively, as they are in other mammals. However, neither plasma LH concentration nor testicular gonadotropin receptor mRNA expression level varied significantly among the sampling months. These results suggest that FSH, inhibin and testosterone have roles in testicular activity in male bears. This study provides important endocrine information for comprehending seasonal reproductivity in male Japanese black bears. PMID- 20364792 TI - Divergent diagnosis from arthroscopic findings and identification of CPII and C2C for detection of cartilage degradation in horses. AB - The objective of this study was to investigate the changes in synovial fluid concentration of collagen type II cleavage site (C2C) and procollagen II C propeptide (CPII), markers of joint cartilage degeneration and synthesis, respectively, in horses with intraarticular fracture or osteochondrosis dissecans (OCD), and to examine the relationship between arthroscopic findings and these biomarker levels. Synovial fluid was collected from 36 joints in 18 horses (6 fractures and 12 OCDs). Samples from contralateral normal joints, when available, served as controls (n = 12). Concentrations of C2C and CPII were measured using enzyme-linked immunosorbant assays. Moreover, the severity of the cartilage degradation was graded arthroscopically in 16 horses, and the correlation between the C2C and CPII levels and the arthroscopic scores were investigated. Compared to the control, the concentration of C2C was increased in OCD joints but not in fracture joints, whereas the concentration of CPII was increased in fracture joints but not in OCD joints. Within each disease group there was no correlation between biomarker levels and arthroscopic findings. Therefore, although C2C and CPII have diagnostic potential further knowledge is required to provide accurate analysis. PMID- 20364793 TI - Evaluation of a new enzyme-linked immunosorbent assay to detect keratan sulfate in equine serum. AB - This study aimed to evaluate a system that identifies cartilage turn over and/or degradation through measurement of a new keratan sulfate (KS) epitope concentration in equine sera. Blood samples were collected from 30 horses, 1 (n = 15) and 2 year-olds (n = 15). Serum samples were analyzed for an epitope of keratan sulfate by 1/20/5D4 (KS5D4) and new epitopes of keratan sulfate using high sensitive keratan sulfate (HSKS), measured by two respective enzyme-linked immunosorbant assays (ELISAs). There was no correlation in serum concentration of KS evaluated using 5D4 and HSKS. Age had no significant effect on concentrations of KS measured with KS5D4 while 1 year-old horses showed significantly higher amounts than 2 year-olds with HSKS. Results suggest that HSKS could detect early signs of cartilage metabolic changes. PMID- 20364794 TI - Development of drug delivery system for erythropoietin as having sustained efficacy with a hydroxyapatite carrier. PMID- 20364795 TI - Dentistry: healthcare that works. PMID- 20364796 TI - Legacy of leadership. Say yes! PMID- 20364798 TI - Personal leadership. PMID- 20364797 TI - Dentistry's critical compass--leadership. PMID- 20364799 TI - The art of leadership. PMID- 20364800 TI - The qualities in outstanding dental leaders. PMID- 20364801 TI - Legacy of leadership. A higher purpose. PMID- 20364802 TI - Leading my new team. PMID- 20364803 TI - Serving without compromise--honoring Dr. David C. Hildebrand. PMID- 20364804 TI - Serious leadership. PMID- 20364805 TI - Leadership happens. PMID- 20364806 TI - Mentoring professionalism: great expectations. PMID- 20364807 TI - Legacy of leadership. Five to be aware of... PMID- 20364809 TI - Internet marketing for dental patients. PMID- 20364808 TI - Dental sleep medicine: an exciting and growing field. PMID- 20364810 TI - Oral and maxillofacial pathology case of the month. Glandular odontogenic cyst. PMID- 20364811 TI - Synthesis and characterization of alkylated poly(1-vinylimidazole) to control the stability of its DNA polyion complexes for gene delivery. AB - Poly(1-vinylimidazole) (PVIm) with alkylated imidazole groups has been synthesized as a pH-sensitive polycation to control the stability of its DNA polyion complexes for gene delivery. The resulting alkylated PVIm (PVIm-R) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurements. Agarose gel retardation assay proved that the alkylated imidazole groups worked as anchor groups to retain DNA. Pyrene fluorescence measurement showed that the hydrophobic domain of the DNA complex with butylated PVIm (PVIm-Bu) increased after the protonation of imidazole groups of the PVIm-Bu to enhance the membrane disruptive activity. The PVIm-Bu exhibited no significant cytotoxicity in spite of the existence of cationic groups. The resulting PVIm-Bu/DNA complexes easily released DNA, as compared with the octylated PVIm, which was examined by competitive exchange with dextran sulfate. As a result, the PVIm-R/DNA complexes mediated efficient gene delivery, and the gene expression depended on the length and density of the alkyl chains. These results suggest that pH-sensitive PVIm-R's control of the stability of DNA polyion complexes enhanced noncytotoxic gene delivery by the optimized alkylated imidazole groups. PMID- 20364812 TI - Covalent and noncovalent phthalocyanine-carbon nanostructure systems: synthesis, photoinduced electron transfer, and application to molecular photovoltaics. PMID- 20364813 TI - Synthesis of alkali metal carboxylates and carboxylic acids using "wet" and "anhydrous" alkali metal hydroxides. PMID- 20364815 TI - Chiral Kagome network from thiacalix[4]arene tetrasulfonate at the interface of aqueous solution/Au(111) surface: an in situ electrochemical scanning tunneling microscopy study. AB - A chiral Kagome network was fabricated at an aqueous solution/Au(111) interface by using a complicated stereo supramolecule thiacalix[4]arene tetrasulfonate as a building block. It opens the possibility to construct a 2D nanoporous network by various functional supramolecules and shows potential application in host-guest chemistry as well as chiral resolution. PMID- 20364814 TI - PbTiO3 nanofibers with edge-shared TiO6 octahedra. AB - A new tetragonal phase of PbTiO(3) was discovered, in which each TiO(6) octahedron pair shares an edge and stacks over following pairs in an interlaced manner to form a one-dimensional (1D) columned structure along the c-axis. This new tetragonal phase of PbTiO(3) transforms into a normal perovskite phase in air at elevated temperature. PMID- 20364816 TI - The puzzle of bond length variation in substituted cyclobutenes. A new example: molecular structure and conformations of 1,2-dimethoxy-3,3,4,4 tetrafluorocyclobut-1-ene. AB - The structure and composition of 1,2-dimethoxy-3,3,4,4-tetrafluorocyclobut-1-ene (DMCB) have been measured by electron diffraction from the gas at a temperature of 370 K with the help of auxiliary data from molecular orbital and normal coordinate calculations, the former at several levels of theory and basis-set size, most importantly B3LYP/cc-pVTZ. The compound was found to exist primarily as a rotamer of C(s) symmetry (ca. 98%; 2sigma = 11%) with the remainder one of C(2v) symmetry; theory predicts about 88% C(s). Values for some of the more important parameters (r(g)/A; angle(alpha)/deg) of the C(s) form are r(C=C) = 1.337(21), r(C1-C4) = 1.496(8), r(C2-C3) = 1.501(8), r(C3-C4) = 1.567(12), r(C1 O) = 1.318(12), r(C2-O) = 1.340(12), r(C3-F) = 1.375(4), r(C4-F) = 1.368(4), angle(ave)(C=C-C) = 94.4(4), angle(ave)(C=C-O) = 133.5(12), angle(ave)(C-O-C) = 119.6(13), and angle(ave)(F-C-F) = 104.4(7). Surprisingly, although electron diffraction values for the fluorinated C3-C4 bond in other cyclobutenes are greater than that for cyclobutene itself, that is not the case for DMCB where it is found to be about the same. Details of the DMCB structure, together with possible reasons for the observed variations in the length of the C3-C4 bond in fluorinated cyclobutene-like molecules, are discussed. PMID- 20364817 TI - Effects of perfluorination on thiophene and pyrrole oligomers. AB - The effect of perfluorination on thiophene and pyrrole oligomers in neutral, cationic, and anionic states was investigated with density functional theory at the (TD)B3P86-30%/6-31G* level. For the title compounds fluorination leads to planarization. For pyrroles a band gap reduction of 0.58 eV results, as unsubstituted pyrroles are nonplanar and disordered in the solid state. For thiophene the band gap is slightly increased as long thiophene oligomers are almost planar. Ionization energies and electron affinities increase upon fluorination by 0.65 and 0.60 eV for polythiophene and by 0.45 and 0.90 eV for polypyrrole. Conduction band widths increase by 0.5 for polythiophene and by 0.7 eV for polypyrrole. Spectra of charged (doped) forms are almost identical to those of the parent systems. Like parent systems, fluorinated oligomers with chain lengths of more than six rings develop a third UV absorption that increases in strength and decreases in energy upon chain length increase. PMID- 20364818 TI - Photoinduced charge separation in a ferrocene-aluminum(III) porphyrin-fullerene supramolecular triad. AB - Light-induced electron transfer is investigated in a ferrocene-aluminum(III) porphyrin-fullerene supramolecular triad (FcAlPorC(60)) and the constituent dyads (AlPorC(60) and FcAlPorPh). The fullerene unit (C(60)) is bound axially to the aluminum(III) porphyrin (AlPor) via a benzoate spacer, and ferrocene (Fc) is attached via an amide linkage to one of the four phenyl groups in the meso positions of the porphyrin ring. The absorption spectra and voltammetry data of the complexes suggest that the ground state electronic structures of the Fc, AlPor, and C(60) entities are not significantly perturbed in the dyads and triad. Time-resolved optical and transient electron paramagnetic resonance (EPR) data show that photoexcitation of the AlPorC(60) dyad results in efficient electron transfer from the excited singlet state of the porphyrin to fullerene, producing the charge-separated state AlPor(*+)-C(60)(*-). The fluorescence and transient EPR data also suggest that some energy transfer from the porphyrin to fullerene may occur. The lifetime of the radical pair AlPor(*+)-C(60)(*-) measured by transient absorbance spectroscopy is found to be 39 ns in o-dichlorobenzene at room temperature. At 200 K, transient EPR experiments place a lower limit of 5 MUs on the radical pair lifetime. In the triad, the data suggest that excitation of the porphyrin gives rise to the charge-separated state Fc(*+)-AlPor-C(60)(*-) in two electron transfer steps. Photocurrent measurements demonstrate that both dyads and the triad have good photovoltaic performance. However, when Fc is appended to AlPorC(60), the expected improvement of the radical pair lifetime and the photovoltaic characteristics is not observed. PMID- 20364819 TI - Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation. AB - Apoptosis signal-regulating kinase 1 (ASK1) is a serine/threonine kinase that responds to a plethora of stress-inducing signals. In turn, activation of ASK1 is associated with a number of human pathological conditions, including neurodegenerative disease, inflammation, and heart failure. In response to oxidative stress, ASK1 activates the cell death-associated p38 MAPK pathway by phosphorylating MKK6. Here, we investigated the regulation of oxidative stress induced ASK1-catalyzed phosphorylation of MKK6. MKK6 phosphorylation levels increased immediately after H(2)O(2) treatment in intact cells and decreased following treatment for 30 min. When expressed in HEK293T cells, ASK1 was reproducibly purified within a high-molecular mass complex ( approximately 1500 kDa) known as the ASK1 signalosome. Measurement of the in vitro kinetic parameters revealed that the catalytic efficiency (k(cat)/K(m)) of ASK1 was 4000 fold greater in cells treated with H(2)O(2) for 3 min than in untreated cells. Interestingly, although the K(m(ATP)) values were found to be unchanged, the K(m(MKK6)) was dramatically decreased ( approximately 1000-fold). The increased affinity was specific for MKK6 and short-lived, as the K(m(MKK6)) returned to basal levels 30 min after treatment. Consistently, endogenous MKK6 was found within the ASK1 signalosome in intact cells and in addition copurified with ASK1 following treatment for 3 min. In contrast, proteins modulating ASK1 activity and degradation were found to interact with the ASK1 signalosome once MKK6 activation was completed. Taken together, these data suggest that oxidative stress rapidly increases ASK1 catalytic efficiency for MKK6 phosphorylation by increasing MKK6 binding affinity within the ASK1 signalosome prior to induction of inactivation and degradation of the complex. PMID- 20364820 TI - Comparison of two metal-dependent pyruvate aldolases related by convergent evolution: substrate specificity, kinetic mechanism, and substrate channeling. AB - HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation. PMID- 20364821 TI - Peptide mass fingerprinting after less specific in-gel proteolysis using MALDI LTQ-Orbitrap and 4-chloro-alpha-cyanocinnamic acid. AB - Peptide Mass Fingerprinting (PMF) of tryptically in-gel digested samples is a well-established protein identification technique for MALDI mass spectrometry but an in-depth PMF evaluation for in-gel digestions of less specific enzymes is still missing. This study demonstrates that the MALDI-LTQ-Orbitrap provides the mass accuracy to gain significant database search results via PMF for the less specific enzymes chymotrypsin and elastase. Additionally, the highly sensitive MALDI matrix ClCCA was compared to the most widely used matrix CHCA by means of the detected peptide number, peptide composition, pI and S/N distribution, sequence coverage, and Mascot score. Therefore, several proteins were in-gel digested by chymotrypsin and elastase. Trypsin and proteinase K were included as references for specific and nonspecific proteases, respectively. Compared to CHCA, ClCCA resulted in a better mapping in all cases of the more complex peptide mixtures generated by less specific enzymes. In summary, the MALDI-LTQ-Orbitrap combined with the matrix ClCCA makes PMF of less specific digests possible in an easy and fast way. Moreover, it opens more possibilities for PMF in the analysis of difficult tasks such as membrane proteins. PMID- 20364822 TI - Aqueous synthesis of zinc blende CdTe/CdS magic-core/thick-shell tetrahedral shaped nanocrystals with emission tunable to near-infrared. AB - We demonstrate the synthesis of near-IR-emitting zinc blende CdTe/CdS tetrahedral shaped nanocrystals with a magic-sized (approximately 0.8 nm radius) CdTe core and a thick CdS shell (up to 5 nm). These high-quality water-soluble nanocrystals were obtained by a simple but reliable aqueous method at low temperature. During the growth of the shell over the magic core, the core/shell nanocrystals change from type I to type II, as revealed by their enormous photoluminescence (PL) emission peak shift (from 480 to 820 nm) and significant increase in PL lifetime (from approximately 1 to approximately 245 ns). These thick-shell nanocrystals have a high PL quantum yield, high photostability, compact size (hydrodynamic diameter less than 11.0 nm), and reduced blinking behavior. The magic-core/thick shell nanocrystals may represent an important step toward the synthesis and application of next-generation colloidal nanocrystals from solar cell conversion to intracellular imaging. PMID- 20364823 TI - Surface acoustic wave nebulization of peptides as a microfluidic interface for mass spectrometry. AB - We describe the fabrication of a surface acoustic wave (SAW) device on a LiNbO(3) piezoelectric transducer for the transfer of nonvolatile analytes to the gas phase at atmospheric pressure (a process referred to as nebulization or atomization). We subsequently show how such a device can be used in the field of mass spectrometry (MS) detection, demonstrating that SAW nebulization (SAWN) can be performed either in a discontinuous or pulsed mode, similar to that for matrix assisted laser desorption ionization (MALDI) or in a continuous mode like electrospray ionization (ESI). We present data showing the transfer of peptides to the gas phase, where ions are detected by MS. These peptide ions were subsequently fragmented by collision-induced dissociation, from which the sequence was assigned. Unlike MALDI mass spectra, which are typically contaminated with matrix ions at low m/z, the SAWN generated spectra had no such interference. In continuous mode, the SAWN plume was sampled on a microsecond time scale by a linear ion trap mass spectrometer and produced multiply charged peptide precursor ions with a charge state distribution shifted to higher m/z compared to an identical sample analyzed by ESI. The SAWN technology also provides the opportunity to re-examine a sample from a flat surface, repeatedly. The process can be performed without the need for capillaries, which can clog, reservoirs, which dilute the sample, and electrodes, which when in direct contact with sample, cause unwanted electrochemical oxidation. In both continuous and pulsed sampling modes, the quality of precursor ion scans and tandem mass spectra of peptides was consistent across the plume's lifetime. PMID- 20364824 TI - Enhancement of molecular ions in mass spectrometry using an ultrashort optical pulse in multiphoton ionization. AB - The spectral domain of an ultraviolet femtosecond laser was expanded by stimulated Raman scattering/four-wave Raman mixing, and the resulting laser pulse was compressed using a pair of gratings. The pulse width was then measured using an autocorrelator comprised of a Michelson interferometer equipped with a multiphoton ionization/mass spectrometer which was used as a two-photon detector. A gas chromatograph/mass spectrometer was employed to analyze triacetone triperoxide (TATP), and the molecular ion induced by multiphoton ionization was substantially enhanced by decreasing the laser pulse width. PMID- 20364825 TI - Ultrafast dynamics of the low-lying 3MLCT states of [Ru(bpy)2(dppp2)]2+. AB - The solvent dependence of the excited state dynamics of [Ru(bpy)(2)(dppp2)](2+) (bpy = 2,2'-bipyridine, dppp2 = pyrido[2',3':5,6]pyrazino[2,3 f][1,10]phenanthroline) were investigated using ultrafast transient absorption spectroscopy. In contrast to the "DNA light-switch" complex [Ru(bpy)(2)(dppz)](2+) (dppz = dipyrido[3,2-a:2',3'-c]phenzine), the structurally related [Ru(bpy)(2)(dppp2)](2+) exhibits discrete formation of the lowest-lying (3)MLCT(dis) (MLCT = metal-to-ligand charge transfer) state from the higher energy (3)MLCT(prox) state in the picosecond time scale. In (3)MLCT(dis) and (3)MLCT(prox), the transferred electron is localized on the portion of the dppp2 ligand distal and proximal to the metal, respectively. The greater dipole moment of (3)MLCT(dis) compared to (3)MCLT(prox), together with the ability of the dppp2 ligand to hydrogen bond, results in a strong dependence of the kinetics of the interconversion process on solvent polarity, decreasing from 67 to 26 ps in CH(2)Cl(2) and CH(3)CN, respectively. Similarly, the lifetime of the emission of the lowest energy state of [Ru(bpy)(2)(dppp2)](2+) also decreases from 273 to 35 ns in the same solvents. In CH(3)CH(2)OH, both the rate of interconversion and the decay of (3)MLCT(dis) are significantly faster, 6.7 ps and 1.7 ns, respectively. Such dependence of the excited state properties is not observed for [Ru(bpy)(2)(dppz)](2+). The results are consistent with the relative stabilization of (3)MLCT(dis) of the dppp2 complex in CH(3)CN compared to CH(2)Cl(2) due to solvent polarity, which may be further stabilized by hydrogen bonding in CH(3)CH(2)OH. PMID- 20364827 TI - Plasmon-enhanced fluorescence from single fluorophores end-linked to gold nanorods. AB - We reported a method to fabricate fluorescent probes preferentially end-linked to Au nanorods. In comparison with organic dyes, the single nanocomplexes provide significant improvement in signal brightness. The bioconjugated nanoantenna structure implicates an approach that is more convenient and amenable to integration for photonic, optoelectronic, and biotechnological applications. PMID- 20364828 TI - UV Photochemical vapor generation sample introduction for determination of Ni, Fe, and Se in biological tissue by isotope dilution ICPMS. AB - A novel, sensitive method is described for the accurate determination of Ni, Se, and Fe in biological tissues by isotope dilution inductively coupled plasma mass spectrometry (ID ICPMS) based on sample introduction arising from online UV photochemical vapor generation (UV-PVG). Volatile species of Ni, Se, and Fe were liberated from a formic acid medium following exposure to a UV source. Sensitivities were enhanced 27- to 355-fold compared to those obtained using pneumatic nebulization sample introduction. Although precision was slightly degraded (a factor of 2) with ultraviolet photochemical mediated vapor generation (UV-PVG), limits of detection (LODs) of 0.18, 1.7, and 1.0 pg g(-1) for Ni, Se, and Fe, respectively, based on an external calibration, provided 28-, 150-, and 29-fold improvements over that realized with conventional pneumatic solution nebulization. Method validation was demonstrated by determination of Ni, Se, and Fe in biological tissue certified reference materials (CRMs) TORT-2 and DORM-3. Concentrations of 2.33 +/- 0.03, 5.80 +/- 0.28, and 109 +/- 2 microg g(-1) (1SD, n = 4) and 1.31 +/- 0.04, 3.35 +/- 0.18, and 353 +/- 5 microg g(-1) (1SD, n = 4) for Ni, Se, and Fe, respectively were obtained in TORT-2 and DORM-3, in good agreement with certified values. PMID- 20364829 TI - Simplifying pyridoxal: practical methods for amino acid dynamic kinetic resolution. AB - Metal complexes of picolinaldehyde are identified as low-cost and environmentally benign catalysts, providing high reaction rates and turnovers for the racemization of amino acids. These pyridoxal surrogates demonstrate activity toward a variety of amino acid esters. Applications to chemoenzymatic dynamic kinetic resolutions provide access to amino acids in high yields and with excellent enantioselectivities, demonstrating their compatibility with protease mediated transformations. PMID- 20364832 TI - Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy. AB - Circulating nucleic acid (CNA) has been the focus of recent research as a noninvasive source of biomarker candidates. Among these markers, DNA fragment size has shown promise for discerning the source of CNA molecules in cancer and prenatal diagnostics. We have developed a one-step assay for analyzing circulating DNA size and quantity directly in human serum. Microfluidic cylindrical illumination confocal spectroscopy and fluorescence burst size analysis are used to individually count and size fluorescently-labeled CNA molecules as they are driven through a microfluidic constriction. First, single molecule sizing was performed on lambda Hind III digest DNA to obtain a size calibration curve. A linear relation between DNA length and burst size was seen from 564 bp to 27.5 kbp. Subsequently, the single molecule assay parameters were optimized. Finally, DNA sizing analysis was performed on serum samples from both early and late stage lung cancer patients. This assay was performed directly in patient serum using only a single reagent, a simple DNA intercalating dye, and without the need for DNA isolation or enzymatic amplification steps. This demonstrates that microfluidic single molecule spectroscopy can be a rapid, facile, and inexpensive alternative to the established PCR-based methods that have been used near exclusively for CNA analysis. PMID- 20364833 TI - Glycal formation in crystals of uridine phosphorylase. AB - Uridine phosphorylase is a key enzyme in the pyrimidine salvage pathway. This enzyme catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1 phosphate (or 2'-deoxyuridine to 2'-deoxyribose 1-phosphate). Here we report the structure of hexameric Escherichia coli uridine phosphorylase treated with 5 fluorouridine and sulfate and dimeric bovine uridine phosphorylase treated with 5 fluoro-2'-deoxyuridine or uridine, plus sulfate. In each case the electron density shows three separate species corresponding to the pyrimidine base, sulfate, and a ribosyl species, which can be modeled as a glycal. In the structures of the glycal complexes, the fluorouracil O2 atom is appropriately positioned to act as the base required for glycal formation via deprotonation at C2'. Crystals of bovine uridine phosphorylase treated with 2'-deoxyuridine and sulfate show intact nucleoside. NMR time course studies demonstrate that uridine phosphorylase can catalyze the hydrolysis of the fluorinated nucleosides in the absence of phosphate or sulfate, without the release of intermediates or enzyme inactivation. These results add a previously unencountered mechanistic motif to the body of information on glycal formation by enzymes catalyzing the cleavage of glycosyl bonds. PMID- 20364834 TI - Cationic Pd(II)-catalyzed Fujiwara-Moritani reactions at room temperature in water. AB - Pd(II)-catalyzed Fujiwara-Moritani reactions can be carried out without external acid at room temperature and in water as the only medium. A highly active cationic Pd(II) catalyst, [Pd(MeCN)(4)](BF(4))(2), easily activates aromatic C-H bonds to produce electron-rich cinnamates in good yields. PMID- 20364835 TI - Gold(I)-mediated C-H activation of arenes. AB - We demonstrate the first Au(I)-mediated C-H activation of arenes. Au(I) salts undergo C-H activation with electron-poor arenes, in stark contrast to Au(III) salts, which activate electron-rich arenes. This operationally simple and highly regioselective process occurs under very mild conditions and gives access to a variety of Au(I)-arene complexes in excellent yields. PMID- 20364836 TI - Coordinatively diverse ortho-phosphinoaniline complexes of ruthenium and isolation of a putative intermediate in ketone transfer hydrogenation catalysis. AB - Amine-functionalized mono- and diphosphines have been used to prepare a series of ruthenium complexes which exhibit a variety of coordination modes depending on the number of donors possessed by the ligands, the degree of amine methylation, the solvent system used, and the oxidation state of the metal. Reactions of the monophosphinoanilines, Ph(2)PAr or Ph(2)PAr' (Ar = o-C(6)H(4)NHMe, Ar' = o C(6)H(4)NMe(2)), with 0.5 equiv of [RuCl(mu-Cl)(eta(6)-p-cymene)](2) in dichloromethane result in the formation of [RuCl(2)(eta(6)-p-cymene)(P-Ph(2)PAr)] or [RuCl(eta(6)-p-cymene)(P,N-Ph(2)PAr')]Cl, respectively. In refluxing methanol, [RuCl(2)(eta(6)-p-cymene)(P-Ph(2)PAr)] gradually undergoes chloride ion dissociation to afford the P,N-chelate, [RuCl(eta(6)-p-cymene)(P,N-Ph(2)PAr)]Cl. This chelate can then be deprotonated to afford the amido complex, [RuCl(eta(6)-p cymene)(P,N-Ph(2)PAr(-))] (Ar(-) = o-C(6)H(4)NMe(-)), which is an active ketone transfer hydrogenation catalyst. Reactions of the diphosphines, Ar(2)PCH(2)PAr(2) (mapm) or Ar'(2)PCH(2)PAr'(2) (dmapm) with 0.5 equiv of [RuCl(mu-Cl)(eta(6)-p cymene)](2) result in the formation of [RuCl(2)(P,P',N,N'-mapm)] or [RuCl(eta(6) p-cymene)(P,P'-dmapm)]Cl, respectively, in which increased methyl substitution in the latter actually inhibits amine coordination with retention of the p-cymene fragment. Reaction of mapm with 1 equiv of [Ru(CO)(4)(eta(2)-C(2)H(4))] in dichloromethane initially produces [Ru(CO)(4)(P-mapm)] which, over a 24 h period with exposure to ambient light, is completely converted to the P,P'-chelate, [Ru(CO)(3)(P,P'-mapm)], by photodissociation of carbon monoxide. The same reaction with 2 equiv of [Ru(CO)(4)(eta(2)-C(2)H(4))] generates a mixture of [Ru(3)(CO)(10)(mu-P,P'-mapm)] and the mononuclear P,P'-chelate. The trinuclear complex can also be synthesized by direct reaction of mapm with 1 equiv of [Ru(3)(CO)(12)]. PMID- 20364837 TI - Can temperature be used to tune the selectivity of membrane ion-selective electrodes? AB - The selectivity coefficients, KIJpot, of ion-selective electrodes (ISEs) have been fundamentally related to thermodynamic parameters, but yet, the effect of temperature on KIJpot has not been studied. We describe a new approach to fine tune the selectivity of ISEs based on the effect of temperature on selectivity coefficients. This effect was quantified for ion exchangers as well as neutral carrier ionophores. Potassium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate was used as an ion exchanger in a poly(vinyl chloride) membrane. The corresponding electrode showed an inverse relationship between log KNa+,K+pot and temperature. Additionally, sodium-selective electrodes using monensin, monensin methyl ester (MME), and monensin decyl ester (MDE) were evaluated as models of electrodes based on neutral carriers. The electrode based on monensin showed an enhancement in the selectivity for sodium over potassium by half an order of magnitude as the temperature increased from 20 to 50 degrees C, while the electrodes based on MME or MDE showed a very small change in selectivity. This can be explained in light of changes in the formation constants between the ions and ionophores with temperature. The theory of the effect of temperature on selectivity for both ion exchangers and neutral carrier ionophores is also discussed. PMID- 20364838 TI - 1-Methyl-3-hydroxy-pyridin-2-one complexes of near infra-red emitting lanthanides: efficient sensitization of Yb(III) and Nd(III) in aqueous solution. AB - The synthesis, X-ray structure, solution stability, and photophysical properties of several trivalent lanthanide complexes of Yb(III) and Nd(III) using both tetradentate and octadentate ligand design strategies and incorporating the 1 methyl-3-hydroxy-pyridin-2-one (Me-3,2-HOPO) chelate group are reported. Both the Yb(III) and Nd(III) complexes have emission bands in the Near Infra-Red (NIR) region, and this luminescence is retained in aqueous solution (Phi(tot)(Yb) approximately 0.09-0.22%).Furthermore, the complexes demonstrate very high stability (pYb approximately 18.8-21.9) in aqueous solution, making them good candidates for further development as probes for NIR imaging. Analysis of the low temperature (77 K) photophysical measurements for a model Gd(III) complex were used to gain an insight into the electronic structure, and were found to agree well with corresponding time-dependent density functional theory (TD-DFT) calculations at the B3LYP/6-311G++(d,p) level of theory for a simplified model monovalent sodium complex. PMID- 20364839 TI - Rapid, sensitive, and label-free impedimetric detection of a single-nucleotide polymorphism correlated to kidney disease. AB - We present a protocol for the very rapid and sensitive detection of a specific mutation of the COL4A5 gene (exon 29, A-C mismatch) which was found in people affected by Alport syndrome (AS) and their families. Disposable electrochemically printed electrodes were used to immobilize a single-stranded oligonucleotide probe that was complementary to the AS-correlated gene. The detection principle is based on changes in the impedance spectra of the redox probe ferro/ferricyanide after hybridization with synthetic target DNA. Detection was performed either for mutated or for healthy (wild-type) gene copies. The high sensitivity obtained with this protocol (LOD in the picomolar range) was additionally enhanced to the femtomolar range by performing the detection in the presence of Ca(2+). In fact, the specific binding of the metal ions in the presence of an A-C nucleotide mismatch induced a further impedance change, thus improving the discrimination between the mutated and healthy gene, as the signal amplification is achieved only for the former. PMID- 20364840 TI - Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides. AB - Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6 31G*. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed. PMID- 20364841 TI - Separation of peptides and oligonucleotides using a monolithic polymer layer and pressurized planar electrophoresis and electrochromatography. AB - The rapid separation of mixtures of six peptides using porous polymer monolithic layers in electrophoresis and pressurized planar electrochromatography modes has been achieved. The separations in the former mode were performed on a generic hydrophobic poly(butyl methacrylate-co-ethylene dimethacrylate) layer with no ionizable functionalities and required 2 min. This layer also enabled the separation of three oligonucleotides. The separation in the pressurized planar electrochromatographic mode was carried out using a negatively charged layer prepared via cografting of 2-acrylamido-2-methyl-1-propanesulfonic acid and 2 hydroxyethyl methacrylate on top of the generic hydrophobic monolith and was completed in 1 min. PMID- 20364842 TI - Characterization of antibody charge heterogeneity resolved by preparative immobilized pH gradients. AB - A capillary isoelectric focusing (cIEF) method has been developed as an alternative to cation exchange chromatography to determine charge heterogeneity for a therapeutic antibody. Characterization of the cIEF profile is important to understand the charged isoform distribution. A variety of preparative IEF methods have been developed over the years but have had various limitations including high levels of contaminating ampholytes and complex fractionation and isolation procedures. More recently, an off-line method that uses pI-based separation on immobilized pH gradients was developed to preparatively isolate material with convenient liquid phase recovery. This method uses the Agilent OFFGEL 3100 Fractionator and was optimized to produce fractions of antibody charge isoforms differing by as little as 0.1 pI units. The isolation of highly resolved fractions then allowed for the identification of N- and C-terminal basic charge modifications including noncyclized glutamine, signal peptide extensions, and various levels of C-terminal lysine processing and high mannose structures. These species could then be correlated to specific peaks in the cIEF profile. This work shows that a preparative IEF method using immobilized pH gradients can be optimized to generate highly resolved, pI-based fractions in solution which can be used for successful cIEF profile characterization. Access to preparative amounts of discrete charged species allows for a better understanding of the underlying covalent modifications responsible for the charge differences and facilitates evaluation of the impact of these modifications on stability and potency of therapeutic antibodies. PMID- 20364843 TI - Polymer-templated nanospider TiO(2) thin films for efficient photoelectrochemical water splitting. AB - We have discovered a facile and inexpensive approach to fabricate "nanospider" TiO(2) thin films with not only an amazing morphology but highly efficient water splitting to produce hydrogen. Our method employs benzene-swollen poly(ethylene glycol) as a sacrificial organic polymer to template the semiconductor thin film. The synthesized TiO(2) thin films are highly crystalline with optimized particle and channel size to enhance the liquid-semiconductor junction interaction. This enhanced contact area leads to more than twice the water splitting performance than conventional P25 thin films. In addition, the nanospider thin films also outperform P25 films in the photodegradation of toxic organics. PMID- 20364844 TI - Photophysical properties of ruthenium(II) polypyridyl-gold(I) ethynyl dyads and triads containing mono- or diethynylphenanthroline incorporated into gold(I) triphenylphosphine organometallics. AB - A new ruthenium(II)-gold(I) dyad, [Ru(bpy)(2){5-{(PPh(3))-Au-C[tripe bond]C} phen}](PF(6))(2) (2), with a different substituted site compared to [Ru(bpy)(2){3 {(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (1), and a triad, [Ru(bpy)(2){3,6 bis{(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (3), with an unsymmetric diethynylphenanthroline relative to [Ru(bpy)(2){3,8-bis{(PPh(3))-Au-C[triple bond]C}-phen}](PF(6))(2) (4) have been prepared. These four ruthenium(II)-gold(I) compounds showed typical metal-to-ligand charge-transfer (MLCT) absorption bands in the 400-550 nm region and a lowest energy pi-pi* absorption involved with the gold(I) perturbation in the 300-400 nm region. Broad emission bands assignable to the triplet MLCT transition were definitely observed in all compounds, indicating that the hybrid architecture constructed with Ru(II)-polypyridyl and Au(I) ethynyl units converts the blue-green gold(I) perturbed pi-pi* phosphorescence into an orange MLCT-based emission. The transient absorption difference spectra of four compounds showed the difference in the electron transfer process between 2 and other compounds 1, 3, and 4 under the excited state. Ru(II)-Au(I) compounds except for 2 receive the supposed charge injection from a ruthenium center to an extended pi-conjugated ethynyl-substituted phenanthroline, which contains one or two gold(I) organometallic unit(s), while 2 undergoes the electron transfer process from the ruthenium center not to the 5-ethynylphenanthroline but to one of the bipyridyl ligands under the excited state. This hypothesis is supported by the deflection of the spots of 2 and [Ru(bpy)(3)](PF(6))(2) from a linear correlation line in a plot of E(0-0) versus DeltaE(1/2), which was based on the electrochemical and emission data of Ru(II)-Au(I) compounds and mononuclear ruthenium(II) polypyridyl complexes. PMID- 20364845 TI - Facts and artifacts in the blinking statistics of semiconductor nanocrystals. AB - Since its initial discovery just over a decade ago, blinking of semiconductor nanocrystals has typically been described in terms of probability distributions for durations of bright, or "on," states and dark, or "off," states. These distributions are obtained by binning photon counts in order to construct a time series for emission intensity and then applying a threshold to distinguish on states from off states. By examining experimental data from CdSe/ZnS core/shell nanocrystals and by simulating this data according to a simple, two-state blinking model, we find that the apparent truncated power-law distributions of on times can depend significantly on the choices of binning time and threshold. For example, increasing the binning time by a factor of 10 can double the apparent truncation time and change the apparent power-law exponent by 30%, even though the binning time is only 3% of the truncation time. Our findings indicate that stringent experimental conditions are needed to accurately determine blinking time probability distributions. Similar considerations should apply to any phenomenon characterized by time series data that displays telegraph noise. PMID- 20364846 TI - Nanostructured hybrid silicon/carbon nanotube heterostructures: reversible high capacity lithium-ion anodes. AB - Lithium-ion batteries have witnessed meteoric advancement the last two decades. The anode area has seen unprecedented research activity on Si and Sn, the two anode alternatives to currently used carbon following the initial seminal work by Fuji on tin oxide nanocomposites. Recent reports on silicon nanowires, porous Si, and amorphous Si coatings on graphite nanofibers (GNF) have been very encouraging. High capacity and long cycle life anodes are still, however, elusive and much needed to meet the ever increasing energy storage demands of modern society. Herein, we report for the first time the synthesis of novel 1D heterostructures comprising vertically aligned multiwall CNTs (VACNTs) containing nanoscale amorphous/nanocrystalline Si droplets deposited directly on VACNTs with clearly defined spacing using a simple two-step liquid injection CVD process. A hallmark of these single reactor derived heterostructures is an interfacial amorphous carbon layer anchoring the nanoscale Si clusters directly to the VACNTs. The defined spacing of nanoscale Si combined with their tethered CNT architecture allow for the silicon to undergo reversible electrochemical alloying and dealloying with Li with minimal loss of contact with the underlying CNTs. The novel heterostructures thus exhibit impressive reversible stable capacities approximately 2050 mAh/g with very good rate capability and an acceptable first cycle irreversible loss approximately 20% comparable to graphitic anodes indicating their promise as high capacity Li-ion anodes. Although warranting further research, particularly with regard to long-term cycling, it can be envisaged that optimization of this simple approach could lead to reversible high capacity next generation Li-ion anodes. PMID- 20364847 TI - Differentiating and apoptotic dose-dependent effects in (-)-alpha-bisabolol treated human endothelial cells. AB - The effect on angiogenesis of (-)-alpha-bisabolol [(-)-6-methyl-2-(4-methyl-3 cyclohexen-1-yl)-5-hepten-2-ol] (1), a widely distributed plant sesquiterpene alcohol, was investigated for the first time. Human endothelial cells treated with 1 were analyzed for their ability to differentiate and organize in microvessels and for their sensitivity to this compound in terms of cytotoxicity and cell growth inhibition. Within 24 h of the treatment with 5 microM 1, cells underwent massive death. Apoptosis induction was responsible for cytotoxicity triggered by 1 as revealed by the release of cytochrome c from the mitochondria, reduction of the Bcl-2/Bax ratio, and caspase 3 activation. At a lower, non apoptotic concentration (0.25 microM), 1 showed a differentiating effect resulting in growth inhibition, invasiveness reduction, and tubule stabilization. PMID- 20364848 TI - Vertex and edge truncated octahedron gold crystals. N-alkylimidazole and silver(I) ion controlled morphology transformation. AB - Two interesting morphology transformations of Au crystals are observed through reacting a mixture of N-alkylimidazole (denoted as C(n)-im, where C(n) = C(n)H(2n+1), and n = 18 and 1), AgNO(3), and HAuCl(4) at 200 degrees C. The long chain C(18)-im with increasing AgNO(3) concentration leads to a progressive truncation of octahedrons at {100} vertices to produce cubes. On the other hand, increasing the concentrations of C(1)-im and AgNO(3), results in a progressive truncation of octahedrons at {110} edges to give rhombic dodecahedrons, which further transform to the unprecedented tetrahexahedrons. The phenomenon could be understood by considering that while both C(18)-im and C(1)-im function as a capping agent with preferential adsorption on Au {111} facets, Ag(+) adsorbs and is subsequently reduced to Ag on Au {110} facets for the sterically demanding C(18)-im, but on the Au {100} facets for C(1)-im. The competition between the growth of the facets protected by imidazole and Ag controls the morphology transformation via truncation of octahedrons at vertices or edges. PMID- 20364849 TI - Three-dimensional porous metal-organic frameworks exhibiting metamagnetic behaviors: synthesis, structure, adsorption, and magnetic properties. AB - Two isomorphous 3D porous metamagnets, {[M(6)(N(3))(12)L(6)].(H(2)O)(13)}(infinity) (M = Ni(II), 1; Co(II), 2), have been constructed from 2-(1,3,4-thiadiazol-2-ylthio)acetic acid (HL), with azido as the auxiliary ligand. Single-crystal X-ray analysis indicates that the complexes possess hexagonal channels with dimensions of about 8.3 A x 8.3 A along the c axis and void space of about 25% per cell volume. Hydrogen adsorption measurements at 740 Torr and 77 K reveal that hydrogen uptakes of 0.68 and 0.83 wt % were observed in 1 and 2, respectively, with BET surface areas of 309 and 328 m(2)/g. Magnetic measurement reveals that both of them exhibit global metamagnetic behaviors resulted from strong intrachain ferromagnetic couplings and weak interchain antiferromagnetic interactions, with critical fields of 22 kOe and 6 kOe for 1 and 2, respectively. PMID- 20364850 TI - Ion distribution in electrified micropores and its role in the anomalous enhancement of capacitance. AB - The distribution of K+ ions in electrified slit-shaped micropores with pore widths ranging from 9.36 to 14.7 A was studied using molecular dynamics simulations. We show that, in slit pores with pore widths between 10 and 14.7 A, the K+ ion distribution differs qualitatively from that described by classical electrical double-layer (EDL) theories in that fully hydrated K+ ions accumulate primarily in the central plane of the slit pores. This phenomenon disappears when the pore width is narrower than 10 A. Ion hydration and water-water interactions, which are rarely considered in prior EDL theories for micropores, are found to be responsible for this behavior. On the basis of these results, we have developed a new sandwich capacitance model to describe the capacitance of the EDLs formed by K+ ions enclosed in slit-shaped micropores. This model is capable of predicting the anomalous enhancement of capacitance experimentally observed in micropores. PMID- 20364851 TI - C-reactive protein induced rearrangement of phosphatidylcholine on nanoparticle mimics of lipoprotein particles. AB - Lipid-coated metal nanoparticles are developed here as a mimic of low-density lipoprotein (LDL) particles and used to study C-reactive protein (CRP) binding to highly curved lipid membranes. A 12 nm shift in the localized surface plasmon resonance (LSPR) was observed when CRP was added to the lipid-coated gold nanoparticles. Transmission electron microscopy (TEM) revealed that CRP induced a structural change to the lipids, resulting in clusters of nanoparticles. This clustering provides a visualization of how CRP could cause the aggregation of LDL particles, which is a key step in atherosclerosis. The cluster formation and resultant LSPR shift requires the presence of both CRP and calcium. Fluorescence anisotropy, using a CRP-specific, fluorophore-labeled aptamer confirmed that CRP was bound to the lipid-coated nanoparticles. An increase in the fluorescence anisotropy (Delta r = +0.261 +/- 0.004) of the aptamer probe occurs in the presence of CRP, PC-coated nanoparticles, and calcium. Subsequent sequestration of calcium by EDTA leads to a decrease in the anisotropy (Delta r = -0.233 +/- 0.011); however, there is no change in the LSPR and no change to the cluster structure observed by TEM. This indicates that CRP binds to the PC membrane on the nanoparticle surface reversibly through a calcium bridging mechanism while changing the underlying membrane structure irreversibly as a result of binding. PMID- 20364852 TI - Ab initio equation of state of the organic molecular crystal: beta-octahydro 1,3,5,7-tetranitro-1,3,5,7-tetrazocine. AB - We apply a simple strategy for calculating from first principles a thermodynamically complete equation of state for molecular crystals using readily available quantum chemistry techniques. The strategy involves a combination of separate methods for the temperature-independent mechanical compression and the thermal vibrational contributions to the free energy. A first principles equation of state for beta-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (beta-HMX) has been calculated for temperatures between 0 and 400 K and for specific volumes from 0.42 to 0.55 cm(3)/g, corresponding to relative volumes from 0.8 to 1.03. The calculated 300 K isotherm agrees very well with the experimentally measured pressure-volume relation. We also discuss thermodynamic properties of the material such as the volumetric thermal expansion coefficient, the Gruneisen parameter, and the specific heat (1.0 kJ/kg/K at 300 K and atmospheric pressure). The developed computational approach exhibits a reliable predictive power and is easily transferable to other molecular materials. PMID- 20364853 TI - Formation of semi-covalent bond in [(N(2)O)(n)H(2)O](+) (n = 2-7) cluster ions studied by IR spectroscopy. AB - IR photodissociation (IRPD) spectra of [(N(2)O)(n)H(2)O](+) with n = 2-7 are measured in the 1100-3800 cm(-1) region. The IRPD spectra show the nu(1) and nu(3) vibrations of the N(2)O components at around 1250 and 2200 cm(-1) and the OH stretching vibrations of the H(2)O part in the 2400-3800 cm(-1) region. In the OH stretching region, the IRPD spectrum of the [(N(2)O)(2)H(2)O](+) ion shows a sharp band at 3452 cm(-1) and a broad one at ~2700 cm(-1), which are assignable to the stretching vibrations of the free and hydrogen-bonded OH groups, respectively. The IRPD spectrum of the [(N(2)O)(3)H(2)O](+) ion displays no band of the free OH stretching vibration; the solvent N(2)O molecules are preferentially hydrogen-bonded to the OH groups. In parallel, the geometry optimization and the vibrational analysis are carried out at the B3LYP/6 311++G(d,p) level of theory. Comparison of the IRPD spectra with the calculated IR spectra suggests that the [(N(2)O)(n)H(2)O](+) cluster ions have an (N(2)O.H(2)O)(+) ion core, in which the positive charge is delocalized over the H(2)O and N(2)O components and that an intermolecular semicovalent bond is formed between the oxygen atoms of H(2)O and N(2)O through the charge resonance interaction. In the clusters larger than n = 3, two solvent N(2)O molecules are strongly hydrogen-bonded to the OH groups, and the other ones are weakly bound to the ion core. The band position of the nu(1) vibration of the solvent N(2)O molecules suggests that the oxygen end of the solvent molecules is bonded to the ion core. PMID- 20364854 TI - Cooperative interaction of hydronium ion with an ethereally fenced hexaarylbenzene-based receptor: an NMR and theoretical study. AB - Using (1)H and (13)C NMR and DFT calculations, the structure and interactions of the symmetric ethereally fenced hexaarylbenzene receptor 1 with hydronium ions were studied. Both 1 and its equimolecular complex 1.H(3)O(+) exhibit C(3v) symmetry. According to DFT, two similar optimal structures of the complex exist, the more stable one being 15.4 kJ/mol lower in energy. The equilibrium between 1 and 1.H(3)O(+) complexes is characterized by the stabilization constant K = 1.97 x 10(6) (i.e., the binding constant eta = 6.3) according to both proton and carbon NMR spectra. The exchange dynamics between 1 and the complex measured by the delay-varied CPMG sequence had to be corrected for the internal exchange processes in both 1 (conformation change) and the complex (vacillation between the two minima). After this correction, the correlation time of exchange was found to be 4.76 x 10(-5) s. Such relatively fast exchange can be explained only by it being mediated by the excess water molecules present in the system. PMID- 20364855 TI - Complexes of C60 with cyclic oligothiophenes: a theoretical study. AB - Complexes of C60 and cyclic and linear oligothiophenes containing 8 and 12 repeating units have been modeled at the M05-2X/6-311G**//M05-2X/6-31G* level of theory. BSSE-corrected binding energies of neutral donor-acceptor complexes vary from 5 to 12 kcal/mol depending on the complex and donor type. Inclusion complexes formed by C60 and cyclooligothiophenes containing 8 repeating units were found to be the most stable ones. Only weak charge transfer from oligothiophene to C60 fragment (<0.1 electron) is observed in the ground state, whereas complete electron transfer from oligothiophene fragment to C60 has been found in the excited state. One electron oxidation or reduction increases binding energies of "tight" complexes and decreases donor-acceptor interaction for "loose" complexes. In the case of cation radicals, positive charge is totally concentrated at the oligothiophene fragment, whereas in anion radicals, negative charge is located at the C60 moiety. Calculations demonstrated that plane oligothiophene conformation and weak binding in a donor-acceptor complex favor the photoinduced charge-carrier formation. PMID- 20364856 TI - Zeta potential of mica covered by colloid particles: a streaming potential study. AB - The streaming potential of mica covered by monodisperse latex particles was measured using the parallel-plate channel, four-electrode cell. The zeta potential of latex bearing amidine charged groups was regulated by the addition of NaCl (10(-4)-10(-2) M) and MgCl(2) (10(-4)-10(-2) M) at a constant pH 5.5 and by the change in pH (4-12) at 10(-2) M NaCl. The size of the latex particles, determined by dynamic light scattering, varied between 502 and 540 nm for the above electrolyte concentration range. Mica sheets have been covered with latex particles under diffusion transport conditions. The latex coverage was regulated by the bulk suspension concentration in the channel and the deposition time. The coverage was determined, with a relative precision of 2%, by the direct enumeration of particles by optical microscopy and AFM. The streaming potential of mica was then determined for a broad range of particle coverage 0 < theta < 0.5, the particle-to-substrate zeta potential ratio zeta(p)/zeta(i), and 8.8 < kappa a < 143 (thin double-layer limit). These experimental data confirmed that the streaming potential of covered surfaces is well reflected by the theoretical approach formulated in ref 32. It was also shown experimentally that variations in the substrate streaming potential with particle coverage for theta < 0.3 and zeta(p)/zeta(i) < 0 are characterized by a large slope, which enables the precise detection of particles attached to interfaces. However, measurements at high coverage and various pH values revealed that the apparent zeta potential of covered surfaces is 1/2(1/2) smaller than the bulk zeta potential of particles (in absolute terms). This is valid for arbitrary zeta potentials of substrates and particles, including the case of negative particles on negatively charged substrates that mimics rough surfaces. Therefore, it was concluded that the streaming potential method can serve as an efficient tool for determining bulk zeta potentials of colloids and bioparticles. PMID- 20364857 TI - Nonequilibrium effects in self-assembled mesophase materials: unexpected supercooling effects for cubosomes and hexosomes. AB - Polar lipids often exhibit equilibrium liquid crystalline structures in excess water, such as the bicontinuous cubic phases (Q(II)) at low temperatures and inverse hexagonal phase (H(II)) at higher temperatures. In this study, the equilibrium and nonequilibrium phase behavior of glyceryl monooleate (GMO) and phytantriol (PHYT) systems in excess water were investigated using both continuous heating and cooling cycles, and rapid temperature changes. Evolution of the phase structure was followed using small-angle X-ray scattering (SAXS). During cooling, not only was supercooling of the liquid crystalline systems by up to 25 degrees C observed, but evidence for nonequilibrium phase structures (not present on heating; such as the gyroid cubic phase only present at low water content in equilibrium) was also apparent. The nonequilibrium phases were surprisingly stable, with return to equilibrium structure for dispersed submicrometer sized particle systems taking more than 13 h in some cases. Inhibition of phase nucleation was the key to greater supercooling effects observed for the dispersed particles compared to the bulk systems. These findings highlight the need for continued study into the nonequilibrium phase structures for these types of systems, as this may influence performance in applications such as drug delivery. PMID- 20364858 TI - Formation of gold particles on nanoscale toroidal DNA assembled with bis(ethylenediamine)gold(III). AB - DNA toroids formed by calf thymus DNA and trivalent cation bis(ethylenediamine)gold(III) are investigated using transmission electron microscopy and dynamic light scattering. Stable dispersions containing toroids with diameters of around 44 nm and thicknesses between 12 and 17 nm are readily prepared. These toroids are shown to be a robust platform for the preparation of metallic nanomaterials. Depending on the reaction conditions, the reduction of gold(III) in their presence can result in either toroids coated with many small (<10 nm) gold particles or larger continuous gold structures. PMID- 20364859 TI - Block copolymer systems: from single chain to self-assembled nanostructures. AB - Recent advances in the field of macromolecular engineering applied to the fabrication of nanostructured materials using block copolymer chains as elementary building blocks are described in this feature article. By highlighting some of our work in the area and accounting for the contribution of other groups, we discuss the relationship between the physical-chemical properties of copolymer chains and the characteristics of nano-objects originating from their self assembly in solution and in bulk, with emphasis on convenient strategies that allow for the control of composition, functionality, and topology at different levels of sophistication. In the case of micellar nanoparticles in solution, in particular, we present approaches leading to morphology selection via macromolecular architectural design, the functionalization of external solvent philic shells with biomolecules (polysaccharides and proteins), and the maximization of micelle loading capacity by the suitable choice of solvent-phobic polymer segments. The fabrication of nanomaterials mediated by thin block copolymer films is also discussed. In this case, we emphasize the development of novel polymer chain manipulation strategies that ultimately allow for the preparation of precisely positioned nanodomains with a reduced number of defects via block-selective chemical reactivity. The challenges facing the soft matter community, the urgent demand to convert huge public and private investments into consumer products, and future possible directions in the field are also considered herein. PMID- 20364860 TI - Selective breast cancer cell capture, culture, and immunocytochemical analysis using self-assembled magnetic bead patterns in a microfluidic chip. AB - Separation and subsequent culturing of MCF-7 breast cancer cells on self assembled protein-coated magnetic beads in a microfluidic chip is demonstrated. The beads were patterned in situ inside a sealed microfluidic channel using magnetic-field-assisted electrostatic self-assembly. Hereafter, they were grafted by exposure to a solution of 5D10 monoclonal antibodies (mAb) and fibronectin (FN), with the first being used for immunospecific cell capture and the latter being used for cell adhesion and growth. A solution of target MCF-7 cells mixed with Jurkat cells was brought inside the microchannel, leading to specific MCF-7 cell capture; the latter were then cultured and evidenced by cell immuno luminescence. PMID- 20364861 TI - Hyperbranched polyphosphates for drug delivery application: design, synthesis, and in vitro evaluation. AB - A water-soluble hyperbranched polyphosphate (HPHEEP) was synthesized through the self-condensation ring-opening polymerization (SCROP) of 2-(2 hydroxyethoxy)ethoxy-2-oxo-1,3,2-dioxaphospholane (HEEP), and its suitability as a drug carrier was then evaluated in vitro. Methyl tetrazolium (MTT) and live/dead staining assays indicated that HPHEEP had excellent biocompatibility against COS-7 cells. The good biodegradability of HPHEEP was observed by NMR analysis, and the degradation products were nontoxic to COS-7 cells. Flow cytometry and confocal laser scanning microscopy analyses suggested that HPHEEP could be easily internalized by vivid cells and preferentially accumulated in the perinuclear region. Furthermore, a hydrophobic anticancer drug, chlorambucil, was used as a model drug and covalently bound to HPHEEP. The chlorambucil dose of the conjugate and free drug required for 50% cellular growth inhibition were 75 and 50 microg/mL, respectively, according to MTT assay against an MCF-7 breast cancer cell line in vitro. This high activity of the conjugate may be attributed to the biodegradability of HPHEEP so as to release the chlorambucil in cells. Therefore, on the basis of its biocompatibility and biodegradability, HPHEEP could provide a charming opportunity to design some excellent drug delivery systems for therapeutic applications. PMID- 20364862 TI - Chemical primer extension at submillimolar concentration of deoxynucleotides. AB - Template-directed primer extension usually requires a polymerase, nucleoside triphosphates, and magnesium ions as cofactors. Enzyme-free, chemical primer extensions are known for preactivated nucleotides at millimolar concentrations. Based on a screen of carbodiimides, heterocyclic catalysts, and reactions conditions, we now show that near-quantitative primer conversion can be achieved at submillimolar concentration of any of the four deoxynucleotides (dAMP, dCMP, dGMP and dTMP). The new protocol relies on in situ activation with EDC and 1 methylimidazole and a magnesium-free buffer that was tested successfully for different sequence motifs. The method greatly simplifies chemical primer extension assays, further reduces the cost of such assays, and demonstrates the potential of the in situ activation approach. PMID- 20364863 TI - Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. PMID- 20364864 TI - Free radicals in L-arginine x HCl x H2O single crystals X-irradiated at 66K- EPR, ENDOR, EIE and DFT studies. AB - X-irradiation of L-arginine hydrochloride monohydrate crystals at 66 K led to at least five radicals detectable with K-band Electron Paramagnetic Resonance (EPR), Electron-Nuclear DOuble Resonance (ENDOR) and ENDOR-induced EPR (EIE) techniques. Radicals R1a and R1b were identified as carboxyl-centered radicals from one electron reduction, (H(2)OOC*)CH (NH(3))(+)(CH(2))(3)NHC(NH(2))(2)(+) in two different conformations arising from the two geometrically distinct molecules of the asymmetric unit in the crystal. Density-Functional Theory (DFT) calculations on cluster models constructed separately for each molecule of the asymmetric unit support the assignments. Radical R2 was identified as the decarboxylation radical, *CH(NH(3))(+)(CH(2))(3)NHC (NH(2))(2)(+). Radical R3, with two proton couplings and one nitrogen coupling, was identified as a radical with the unpaired electron localized on the guanidyl group, ( )(OOC)CH(NH(3))(+)(CH(2))(3)NHC*(NH(2))(2)(+). R3 is a product of one-electron reduction different from radicals R1a and R1b. DFT calculations on a cluster model reproduced the experimental values very well and thus supported the assignment of R3. Geometry optimization indicated that the guanidyl group transformed from planar to pyramidal upon trapping the electron. Radical R4 was identified as a side chain dehydrogenation radical, ( )(OOC)CH(NH(3))(+)(CH(2))(2)*CH NHC(NH(2))(2)(+). It was not possible to collect sufficient data to identify radical R5, although it clearly exhibited hyperfine coupling to one nonexchangeable beta-proton. PMID- 20364865 TI - Biotransformation of hop-derived monoterpene alcohols by lager yeast and their contribution to the flavor of hopped beer. AB - It is well-known that various beers contain many flavor compounds derived from barley malts, hops, yeast fermentation, and other raw materials. Among these flavor compounds, terpenoids are mainly derived from hops. Linalool, one of the monoterpene alcohols, has been found in various beers and been regarded as an important factor for a hop-derived beer flavor. We focus on contributions of other monoterpene alcohols (geraniol, beta-citronellol, nerol, and alpha terpineol) to hopped beer flavor. Several researchers have reported that monoterpene alcohols are biotransformed by yeast and that geraniol is mainly transformed to beta-citronellol during the first 2-4 days in model fermentation. In this study, we investigated the biotransformation of monoterpene alcohols during fermentation of hopped beer by using various hop cultivars. As a result, geraniol drastically decreased during the first 3 days. beta-Citronellol was almost absent in wort and gently increased during the total fermentation period. The concentrations of geraniol and beta-citronellol in finished beer increased, depending on the initial concentration of geraniol in the wort. The continuous increase of beta-citronellol did not correspond to the fast decrease of geraniol. This increase of beta-citronellol might be partly explained by an occurrence of glycosidically bound flavor precursor and a glucoside hydrolase activity secreted from lager yeast. In addition, we examined flavor characteristics of monoterpene alcohols and found that there was an additive effect among linalool, geraniol, and beta-citronellol and that only 5 microg/L of geraniol and beta-citronellol were enough for this effect. Therefore, it is suggested that not only linalool but also geraniol and beta-citronellol might contribute to hopped beer flavor at lower levels, at which OAVs of these compounds become below 1.0. PMID- 20364866 TI - Peptide adsorption to cyanine dye aggregates revealed by cryo-transmission electron microscopy. AB - The binding interaction between aggregates of the 5-chloro-2-[[5-chloro-3-(3 sulfopropyl)-3H-benzothiazol-2-ylidene]methyl]-3-(3-sulfopropyl)benzothiazolium hydroxide inner salt ammonium salt (CD-1) and alpha-helix, as well as beta-sheet forming de novo designed peptides, was investigated by absorption spectroscopy, circular dichroism spectroscopy, and cryogenic transmission electron microscopy. Both pure dye and pure peptides self-assembled into well-defined supramolecular assemblies in acetate buffer at pH = 4. The dye formed sheetlike and tubular H- and J-aggregates and the peptides alpha-helical coiled-coil assemblies or beta sheet rich fibrils. After mixing dye and peptide solutions, tubular aggregates with an unusual ultrastructure were found, most likely due to the decoration of dye tubes with monolayers of peptide assemblies based on the strong electrostatic attraction between the oppositely charged species. There was neither indication of a transfer of chirality from the peptides to the dye aggregates nor the opposite effect of a structural transfer from dye aggregates onto the peptides secondary structure. PMID- 20364867 TI - Hopane-type triterpenes and binaphthopyrones from the scale insect pathogenic fungus Aschersonia paraphysata BCC 11964. AB - Two new triterpenes, 17(21)-hopene-6alpha,12beta-diol (1) and 17(21)-hopen-12beta ol (2), the known 17(21)-hopen-6alpha-ol (zeorinin, 3), and two new biarylic dihydronaphthopyrones, aschernaphthopyrones A (4) and B (5), were isolated from the scale insect pathogenic fungus Aschersonia paraphysata BCC 11964. Hopene 1 and aschernaphthopyrone A (4) exhibited antimalarial activity with IC(50) values of 15 and 7.3 microM, respectively. PMID- 20364868 TI - Golden rule for buttressing vulnerable soluble proteins. AB - Local weaknesses in the structure of soluble proteins have received little attention. The structure may be inherently weak at sites where hydration of the protein backbone is locally hampered by formation of an intramolecular hydrogen bond which in turn is not fully stabilized through burial within a hydrophobic environment. The result is insufficient compensation for the thermodynamic cost of dehydrating the backbone polar groups. This work shows that these structural deficiencies, the unburied backbone hydrogen bonds, are compensated in natural proteins by disulfide bonds that are needed to maintain the structural integrity. Examination of all PDB-reported soluble structures reveals that, after suitable normalization, the number of disulfide bonds, X, correlates tightly with the number of unburied backbone hydrogen bonds, Y, beyond the baseline level Y = 20, revealing a simple balance relation: Y = 5X + 20. This equation introduces a 1:5 ratio associated with the buttressing of soluble proteins with structural deficiencies. The results are justified on thermodynamic grounds and have implications for biomolecular engineering as they introduce two constants of universal applicability determining the architecture of soluble proteins. PMID- 20364869 TI - Space-based constraints on spatial and temporal patterns of NO(x) emissions in California, 2005-2008. AB - We describe ground and space-based measurements of spatial and temporal variation of NO(2) in four California metropolitan regions. The measurements of weekly cycles and trends over the years 2005-2008 observed both from the surface and from space are nearly identical to each other. Observed decreases in Los Angeles and the surrounding cities are 46% on weekends and 9%/year from 2005-2008. Similar decreases are observed in the San Francisco Bay area and in Sacramento. In the San Joaquin Valley cities of Fresno and Bakersfield weekend decreases are much smaller, only 27%, and the decreasing trend is only 4%/year. We describe evidence that the satellite observations provide a uniquely complete view of changes in spatial patterns over time. For example, we observe variations in the spatial pattern of weekday-weekend concentrations in the Los Angeles basin with much steeper weekend decreases at the eastern edge of the basin. We also observe that the spatial extent of high NO(2) in the San Joaquin Valley has not receded as much as it has for other regions in the state. Analysis of these measurements is used to describe observational constraints on temporal trends in emission sources in the different regions. PMID- 20364870 TI - Core-perfluoroalkylated perylene diimides and naphthalene diimides: versatile synthesis, solubility, electrochemistry, and optical properties. AB - By a strategy featuring perfluoroalkylation of the highly soluble intermediates and their further efficient transformations to target compounds, a versatile synthesis of core-perfluoroalkylated perylene diimides (PDIs) and naphthalene diimides (NDIs) was developed, and PDIs perfluoroalkylated at 1-position or 1,6 positions and core-perfluoroalkylated NDIs were first obtained. By esterification, perfluoroalkylation, hydrolysis, and condensation with amine, 1 perfluorooctyl-PDIs (7b, 7c, and 7e), 1,7-bis(perfluorooctyl)-PDIs (8a-c and 8e g), 1,6-bis(perfluorooctyl)-PDIs (8'e), a mixture of 1,7-bis(trifluoromethyl) PDIs and 1,6-bis(trifluoromethyl)-PDIs (11b and 11'b, 11d and 11'd, in a ratio of 19:1), 2-perfluorooctyl-NDIs (20a-d), and 2,6-bis(perfluorooctyl)-NDIs (21a-21d) were efficiently synthesized. Five valuable intermediates--1 perfluorooctylperylene dianhydride (5), 1,7-bis(perfluorooctyl)perylene dianhydride (6) 1,6-bis(perfluorooctyl)perylene dianhydride (6'), 2 perfluorooctylnaphthalene dianhydride (18), and 2,6-bis(perfluorooctyl) naphthalene dianhydride (19)--were also obtained, and they can condense with many amines to produce PDIs containing different functional side chains on the imide nitrogen atoms. Solubility, electrochemistry, and optical properties of the above core-perfluoroalkylated PDIs and NDIs were investigated. Core-perfluoroalkylated 8e, 8f, 8'e, mixture of 11d and 11'd, 20b, and 20d with excellent solubility in common organic solvents are competitive as candidates as solution processable semiconductors. Core-perfluoroalkylated PDIs and NDIs with experimental LUMO energy of 4.04-4.34 eV demonstrate strong electron accepting ability. For core perfluoroalkylated PDIs, the maximum absorptions display blue shifts of 6-18 nm and the maximum molar extinction coefficients decrease obviously relative to those of unsubstituted PDIs, and they inherit the strong fluorescence from the PDIs family, which makes them promising fluorescent dyes. PMID- 20364871 TI - Microbial inactivation of Pseudomonas putida and Pichia pastoris using gene silencing. AB - Antisense deoxyoligonucleotide (ASO) gene silencing was investigated as a potential disinfection tool for industrial and drinking water treatment application. ASOs bind with their reverse complementary mRNA transcripts thereby blocking protein translation. While ASO silencing has mainly been studied in medicine, it may be useful for modulating gene expression and inactivating microorganisms in environmental applications. In this proof of concept work, gene targets were sh ble (zeocin resistance) and todE (catechol-2,3-dioxygenase) in Pichia pastoris and npt (kanamycin resistance) in Pseudomonas putida. A maximum 0.5-fold decrease in P. pastoris cell numbers was obtained following a 120 min incubation with single-stranded DNA (ssDNA) concentrations ranging from 0.2 to 200 nM as compared to the no ssDNA control. In P. putida, a maximum 5.2-fold decrease was obtained after 90 min with 400 nM ssDNA. While the silencing efficiencies varied for the 25 targets tested, these results suggest that protein activity as well as microbial growth can be altered using ASO gene silencing based tools. If successful, this technology has the potential to eliminate some of the environmental and health issues associated with the use of strong chemical biocides. However, prior to its dissemination, more research is needed to increase silencing efficiency and develop effective delivery methods. PMID- 20364872 TI - Use of the Diels-Alder adduct of pyrrole in organic synthesis. Formal racemic synthesis of Tamiflu. AB - A new synthetic route to Tamiflu was developed via the Diels-Alder reaction of pyrrole and bromoacetylene. PMID- 20364873 TI - Expert performance in sport and the dynamics of talent development. AB - Research on expertise, talent identification and development has tended to be mono-disciplinary, typically adopting genocentric or environmentalist positions, with an overriding focus on operational issues. In this paper, the validity of dualist positions on sport expertise is evaluated. It is argued that, to advance understanding of expertise and talent development, a shift towards a multidisciplinary and integrative science focus is necessary, along with the development of a comprehensive multidisciplinary theoretical rationale. Here we elucidate dynamical systems theory as a multidisciplinary theoretical rationale for capturing how multiple interacting constraints can shape the development of expert performers. This approach suggests that talent development programmes should eschew the notion of common optimal performance models, emphasize the individual nature of pathways to expertise, and identify the range of interacting constraints that impinge on performance potential of individual athletes, rather than evaluating current performance on physical tests referenced to group norms. PMID- 20364874 TI - The maximal accumulated oxygen deficit method: a valid and reliable measure of anaerobic capacity? AB - The maximal accumulated oxygen deficit (MAOD) method has been extensively, but unfortunately not very methodically, used; the procedure used to determine the MAOD varies considerably. Therefore, this review evaluates the effect of different numbers and durations of submaximal exercise bouts on the linear power output (PO)-oxygen uptake ((.)VO2) relationship and thus the MAOD. Changing the number and duration of the submaximal exercise bouts substantially influences the calculated MAOD when relatively long submaximal exercise bouts are used and no fixed value of the y-intercept is forced into the linear regression line. This is most likely due to non-linearity of the PO-(.)VO2 relationship for exercise intensities above the lactate threshold (LT). Non-linearity of the PO-(.)VO2 relationship is probably caused by the development of a slow component in (.)VO2 during submaximal exercise at intensities above the LT. Thus, it is important to standardize the number, duration and intensity of submaximal exercise bouts necessary to establish the PO-(.)VO2 relationship. Beyond changing the number and duration of the submaximal exercise bouts, the effect of different supramaximal exercise bouts on the calculated MAOD has been investigated. While it has become clear that different exercise protocols result in relatively similar values of the MAOD, a closer look at individual data suggests that it may be important to choose an exercise protocol that is representative of the athlete's event. The validity of the MAOD method was studied by different authors comparing the MAOD with metabolic measurements of anaerobic adenosine triphosphate (ATP) production. The main limitation with the metabolic measurements of anaerobic ATP production from muscle biopsy data is that the active muscle mass is unknown, which makes it hard to accurately study the validity of the MAOD method. From the studies that evaluated the reliability of the MAOD method it is clear that the MAOD method may not be a reliable measure of anaerobic capacity. From these findings it can be concluded that the MAOD method may have limitations as a valid and reliable measure of anaerobic capacity and needs to be further improved. We suggest the use of 10 x 4 minute submaximal exercise bouts and a fixed value of the y intercept for the construction of the linear PO-(.)VO2 relationship, after which the MAOD can be determined during a supramaximal exercise protocol specific for the athlete's event. This method will lead to a more robust PO-(.)VO2 relationship and will therefore result in more valid and reliable results. PMID- 20364875 TI - A biomechanical evaluation of resistance: fundamental concepts for training and sports performance. AB - Newton's second law of motion describes the acceleration of an object as being directly proportional to the magnitude of the net force, in the same direction as the net force and inversely proportional to its mass (a = F/m). With respect to linear motion, mass is also a numerical representation of an object's inertia, or its resistance to change in its state of motion and directly proportional to the magnitude of an object's momentum at any given velocity. To change an object's momentum, thereby increasing or decreasing its velocity, a proportional impulse must be generated. All motion is governed by these relationships, independent of the exercise being performed or the movement type being used; however, the degree to which this governance affects the associated kinematics, kinetics and muscle activity is dependent on the resistance type. Researchers have suggested that to facilitate the greatest improvements to athletic performance, the resistance training programme employed by an athlete must be adapted to meet the specific demands of their sport. Therefore, it is conceivable that one mechanical stimulus, or resistance type, may not be appropriate for all applications. Although an excellent means of increasing maximal strength and the rate of force development, free-weight or mass-based training may not be the most conducive means to elicit velocity-specific adaptations. Attempts have been made to combat the inherent flaws of free weights, via accommodating and variable resistance training devices; however, such approaches are not without problems that are specific to their mechanics. More recently, pneumatic-resistance devices (variable) have been introduced as a mechanical stimulus whereby the body mass of the athlete represents the only inertia that must be overcome to initiate movement, thus potentially affording the opportunity to develop velocity-specific power. However, there is no empirical evidence to support such a contention. Future research should place further emphasis on understanding the mechanical advantages/disadvantages inherent to the resistance types being used during training, so as to elicit the greatest improvements in athletic performance. PMID- 20364876 TI - Intravenous versus oral rehydration in athletes. AB - Fluid is typically administered via intravenous (IV) infusion to athletes who develop clinical symptoms of heat illness, based on the perception that dehydration is a primary factor contributing to the condition. However, other athletes also voluntarily rehydrate with IV fluid as opposed to, or in conjunction with, oral rehydration. The voluntary use of IV fluids to accelerate rehydration in dehydrated, though otherwise healthy athletes, has recently been banned by the World Anti-Doping Agency. However, the technique remains appealing to many athletes. Given that it now violates the Anti-Doping Code, it is important to determine whether potential benefits of using this technique outweigh the risks involved. Several studies have shown that rehydration is more rapid with IV fluid. However, the benefits are generally transient and only small differences to markers of hydration status are seen when comparing IV and oral rehydration. Furthermore, several studies have shown improvements in cardiovascular function and thermoregulation with IV fluid, while others have indicated that oral fluid is superior. Subsequent exercise performance has not been improved to a greater extent with one technique over the other. The paucity of definitive findings is probably related to the small number of studies investigating these variables and the vast differences in the designs of studies that have been conducted. The major limitation of IV rehydration is that it bypasses oropharyngeal stimulation, which has an influence on factors such as thirst sensation, antidiuretic hormone (arginine vasopressin) release, cutaneous vasodilation and mean arterial pressure. Further research is necessary to determine the relative benefits of oral and IV rehydration for athletes. PMID- 20364877 TI - Match analysis and the physiological demands of Australian football. AB - Australian Football, the most popular football code in Australia, is a contact sport played by two teams of 18 players who contest play over four 20-minute quarters; the object of the game is to score the most points through goal kicking. Sixteen professional senior sides compete against each other in the Australian Football League (AFL) and, similar to other football codes, game demands at the elite level in the AFL have changed considerably in recent years. Early time-motion analysis studies highlighted the long periods of time players spent in low intensity activities (standing and walking). While recent studies utilizing global positioning systems (GPS) technology are somewhat in agreement with earlier findings, available evidence suggests that the game is getting faster. For example, 'playing on' after a mark (a feature of the game where players who catch the ball on the full from a kick longer than 15 m are awarded a free kick) is now much quicker. Indeed, rule changes in recent years have increased the flow and speed of the game; there has been a reduction in the time taken for umpires to restart play, and for players to kick-in (after the opposition kicks a behind) or take a set shot at goal. Nomadic players (a broad term for midfielders and ruckmen because they follow play over the entire playing field) cover slightly greater distances (12,310 m) than both forwards (11,920 m) and backs (11,880 m) in a game. Compared with players in other positions, midfielders are consistently found to spend the most time at higher intensities (running and sprint efforts with movement velocities > 4.44 m/sec), complete more high intensity efforts (approximately 98 per game), sustain them for longer and have shorter recovery periods between high intensity exercise bouts (approximately 90 seconds on average). 'Ruckmen' have similar but less intense running profiles, while forwards and backs generally have less game involvement but have a more intermittent running profile (longer recovery periods with shorter duration high intensity exercise bouts and less time spent in constant pace running). Endurance fitness remains very important for players at the elite level of competition, as does upper and lower body strength and power. In addition, given the increasing speed at which Australian Football is now played, repeated sprint ability of players is arguably more important now than it was in previous years. There are no significant differences in these measures between playing position. Similarly, speed over 10-40 m does not appear to differ between playing position. Establishing the reliability of distance and velocity-derived GPS data in highly specific game-related activities is needed; once achieved, GPS data have the potential to accurately inform coaches of the position-specific demands on their players and to drive the development of training practices that reflect the changing demands of the game. PMID- 20364878 TI - Differential effects on effort discounting induced by inactivations of the nucleus accumbens core or shell. AB - The authors investigated the contribution of the nucleus accumbens (NAc) core and shell to effort-based decision making using a discounting procedure. Selection of 1 lever delivered a smaller, 2-pellet reward immediately, whereas the other lever delivered a 4-pellet reward after a fixed ratio of presses (2, 5, 10, or 20) that increased over 4 blocks of 10 discrete choice trials. Subsequent testing employed an equivalent delays procedure, whereby the relative delay to reward delivery after selection of either option was equalized. In well-trained rats, inactivation of the core, but not the shell, via infusion of GABA A/B agonists muscimol/baclofen reduced preference for the high-effort option under standard conditions and also when rats were tested using an equivalent delays procedure. However, inactivation of the core did not alter preference for 4-pellet versus 2 pellet rewards when the relative costs of each option were the same (1 press). Thus, the NAc core, but not the shell, appears to be part of a neural circuit that biases choice toward larger rewards associated with a greater effort cost. Furthermore, the contributions by the NAc core to this form of decision making can be dissociated from its role in delay discounting. PMID- 20364879 TI - Autonomic, behavioral, and neural analyses of mild conditioned negative affect in marmosets. AB - Avoidance and alerting behaviors and accompanying physiological responses, including changes in heart rate (HR), are core components of negative emotion. Investigations into the neural mechanisms underlying the regulation and integration of these responses require animal models that simultaneously measure both the physiological and behavioral components of emotion. A primate model is of particular importance in view of the well developed prefrontal cortex of primates, and this region's critical role in emotion regulation and the etiology of affective disorders. Therefore, we have developed a simple aversive conditioning paradigm to assess, simultaneously, cardiovascular and behavioral responses in the marmoset (Callithrix jacchus). Validation of the paradigm was achieved by (1) comparing conditioned responses to a predictive cue with pseudoconditioned responses to a nonpredictive cue; (2) assessing the acquisition of conditioning following lesions of the amygdala, a region essential for associative learning in humans and rats; and (3) determining the contributions of the sympathetic and parasympathetic nervous system to the conditioned autonomic responses. Marmosets acquired conditioned HR and behavioral responses in the conditioned, but not the pseudoconditioned or amygdala lesioned groups. Conditioned HR accelerations were reduced by both parasympathetic and sympathetic blockade. Thus, a model of associative learning of mild negative emotion in the marmoset has been validated by psychological, neurological, and pharmacological investigation. Future studies will determine the role of the prefrontal cortex in the regulation of these negative emotional responses, to provide insights into the neuropathology of affective disorders. PMID- 20364880 TI - A role for alpha-adrenergic receptors in extinction of conditioned fear and cocaine conditioned place preference. AB - Previous work has demonstrated an important role for adrenergic receptors in memory processes in fear and drug conditioning paradigms. Recent studies have also demonstrated alterations in extinction in these paradigms using drug treatments targeting beta- and alpha2-adrenergic receptors, but little is known about the role of alpha-adrenergic receptors in extinction. The current study examined whether antagonism of alpha-adrenergic receptors would impair the consolidation of extinction in fear and cocaine conditioned place preference paradigms. After contextual fear conditioning, injections of the alpha-adrenergic receptor antagonist prazosin (1.0 or 3.0 mg/kg) following nonreinforced context exposures slowed the loss of conditioned freezing over the course of 5 extinction sessions (Experiment 1). After cocaine place conditioning, prazosin had no effect on the rate of extinction over 8 nonreinforced test sessions. Following postextinction reconditioning, however, prazosin-treated mice showed a robust place preference, but vehicle-treated mice did not, suggesting that prazosin reduced the persistent effects of extinction (Experiment 2). These results confirm the involvement of the alpha-adrenergic receptor in extinction processes in both appetitive and aversive preparations. PMID- 20364881 TI - Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite. AB - Our laboratory has reported that manipulations that provoke a robust sodium appetite (e.g., sodium depletion, deoxycorticosterone acetate) decrease lateral hypothalamic self-stimulation (LHSS) reward if rats are denied access to hypertonic saline solutions. The following studies investigated the interaction between chronic sodium appetite and the renin-angiotensin-aldosterone system on LHSS reward. In Experiment 1, animals treated with the diuretic furosemide (20 mg/kg) when denied access to saline exhibited an increase in the current required to produce 50% of the maximum LHSS response rate (ECu50) 48 hr after extracellular volume depletion. Furosemide-depleted rats that were allowed to drink 0.3 M saline after depletion, or that were treated with the selective mineralocorticoid receptor (MR) antagonist spironolactone, which significantly reduced sodium appetite, did not show ECu50 changes. In Experiment 2 chronic intracerebroventricular administration of the selective MR antagonist RU 28318 (10 microg/microl/hr) prevented decreases in the ECu50 induced by deoxycorticosterone acetate-no salt treatment. We conclude that an unresolved sodium appetite will reduce responding for rewards and that experimental manipulations that reduce sodium appetite (e.g., access to saline or blockade of MR) decrease hedonic deficits. PMID- 20364882 TI - Suppression of third ventricular NPY-elicited feeding following medullary reticular formation infusions of muscimol. AB - The appetitive component of feeding is controlled by forebrain substrates, but the consummatory behaviors of licking, mastication, and swallowing are organized in the brainstem. The target of forebrain appetitive signals is unclear but likely includes regions of the medullary reticular formation (RF). This study was undertaken to determine the necessity of different RF regions for mastication induced by a descending appetitive signal. We measured solid food intake in response to third ventricular (3V) infusions of the orexigenic peptide neuropeptide Y 3-36 in awake, freely moving rats and determined whether focal RF infusions of the GABAA agonist muscimol suppressed eating. RF infusions were centered in either the lateral tegmental field, comprising the intermediate (IRt) and parvocellular (PCRt) RF, or in the nucleus gigantocellularis (Gi). Infusions of NPY 3-36 (5 microg/5 microl) into 3V significantly increased feeding of solid food over a 90-min period compared with the noninfused condition (4.3 g +/- 0.56 vs. 0.57 g +/- 0.57, p < .001). NPY 3-36-induced food intake was suppressed (1.7 g +/- 0.48) by simultaneous infusions of muscimol (0.6 mM/100 nl) into the IRt/PCRt (p < .01). Coincident with the decrease in feeding was a decrease in the amplitude of anterior digastric muscle contractions in response to intraoral sucrose infusions. In contrast, infusions of muscimol into Gi had no discernible effect on food intake or EMG amplitude. These data suggest that the IRt/PCRt is essential for forebrain-initiated mastication, but that the Gi is not a necessary link in this pathway. PMID- 20364884 TI - Stress reduces use of negative feedback in a feedback-based learning task. AB - In contrast to the well-established effects of stress on learning of declarative material, much less is known about stress effects on reward- or feedback-based learning. Differential effects on positive and negative feedback especially have received little attention. The objective of this study, thus, was to investigate effects of psychosocial stress on feedback-based learning with a particular focus on the use of negative and positive feedback during learning. Participants completed a probabilistic selection task in both a stress and a control condition. The task allowed quantification of how much participants relied on positive and negative feedback during learning. Although stress had no effect on general acquisition of the task, results indicate that participants used negative feedback significantly less during learning after stress compared with the control condition. An enhancing effect of stress on use of positive feedback failed to reach significance. These findings suggest that stress acts differentially on the use of positive and negative feedback during learning. PMID- 20364883 TI - Conjunctive encoding of movement and reward by ventral tegmental area neurons in the freely navigating rodent. AB - As one of the two main sources of brain dopamine, the ventral tegmental area (VTA) is important for several complex functions, including motivation, reward prediction, and contextual learning. Although many studies have identified the potential neural substrate of VTA dopaminergic activity in reward prediction functions during Pavlovian and operant conditioning tasks, less is understood about the role of VTA neuronal activity in motivated behaviors and more naturalistic forms of context-dependent learning. Therefore, VTA neural activity was recorded as rats performed a spatial memory task under varying contextual conditions. In addition to reward- and reward predicting cue-related firing commonly observed during conditioning tasks, the activity of a large proportion of VTA neurons was also related to the velocity and/or acceleration of the animal's movement. It is important to note that movement-related activity was strongest when rats displayed more motivation to obtain reward. Furthermore, many cells displayed a dual code of movement- and reward-related activity. These two modes of firing, however, were differentially regulated by context information, suggesting that movement- and reward-related firing are two independently regulated modes of VTA neuronal activity and may serve separate functions. PMID- 20364885 TI - Influence of smell loss on taste function. AB - The influence of damage to one sensory system on the functioning of other sensory systems has been of scientific interest for over a century. Recently it has been suggested that damage to the olfactory system (CN I) decreases the ability to taste; that is, to perceive sweet, sour, bitter and salty sensations via CN VII, IX, and X. If true, this would be in contrast to most other sensory systems, where compromise typically leads to either cross-modal enhancement of function or to no effects at all. In the present study, data from both regional and whole mouth taste tests of 581 patients presenting to a smell and taste center with varying degrees of olfactory function were evaluated to address whether olfactory loss is associated with taste loss. No significant influence of olfactory dysfunction on any measure of taste perception was found when the effects of sex, age, and etiology were controlled. These data suggest that smell loss, per se, has no meaningful influence on taste function, and that clinical associations between smell and taste dysfunction, when observed, likely reflect comorbid influences. PMID- 20364887 TI - Sexual orientation and the second to fourth finger length ratio: a meta-analysis in men and women. AB - The ratio of the lengths of the second and fourth fingers (2D:4D) may serve as a marker for prenatal androgen signaling. Because people are typically unaware of their 2D:4D, its use allows possible effects of early sex hormone regimes and socialization to be disentangled. We conducted a meta-analysis on relationships between 2D:4D and sexual orientation in men and women in 18 independent samples of men and 16 independent samples of women. Collectively, these samples comprised 1,618 heterosexual men, 1,693 heterosexual women, 1,503 gay men, and 1,014 lesbians. In addition to identifying the normative heterosexual sex difference in 2D:4D for both hands, we found that heterosexual women had higher (more feminine) left- and right-hand 2D:4D than did lesbians, but we found no difference between heterosexual and gay men. Moderator analyses suggested that ethnicity explained some between-studies variation in men. These results add to a literature suggesting that early sex hormone signaling affects sexual orientation in women, and highlight the need for further research exploring the relationships among 2D:4D, sexual orientation, and ethnicity in men. PMID- 20364888 TI - Stress impairs retrieval of socially relevant information. AB - Several studies have reported that stress impairs memory retrieval, even though findings are not unequivocal. Moreover, memory for socially relevant information was not previously investigated. The present study aimed to test the effects of stress on the retrieval of social memory (e.g., memory concerning names, birthdays, or biographies). In a randomized cross-over experiment, the cognitive performance of 29 subjects (15 women) was tested twice. Social memory was tested in a stress session, in which participants were exposed to a brief standardized psychosocial laboratory stressor between encoding and retrieval. Performance was compared with a stress-free control session. Stress exposure caused an increase in cortisol concentrations and changes in several mood measures. Social memory retrieval was reduced in the stress compared with the control session. An association between the cortisol stress response and poorer retrieval was significant in responders, that is, those participants displaying a cortisol rise after stress onset. Thus, similar to other forms of declarative memory, the retrieval of declarative memory for socially relevant information learned from biographical notes is impaired after acute stress exposure. This effect is linked to the stress-induced cortisol increase. PMID- 20364886 TI - Sensitivity of the mouse to changes in azimuthal sound location: angular separation, spectral composition, and sound level. AB - Auditory spatial acuity was measured in mice using prepulse inhibition (PPI) of the acoustic startle reflex as the indicator response for stimulus detection. The prepulse was a "speaker swap" (SSwap), shifting a noise between two speakers located along the azimuth. Their angular separation, and the spectral composition and sound level of the noise were varied, as was the interstimulus interval (ISI) between SSwap and acoustic startle reflex elicitation. In Experiment 1 a 180 degrees SSwap of wide band noise (WBN) was compared with WBN Onset and Offset. SSwap and WBN Onset had near equal effects, but less than Offset. In Experiment 2 WBN SSwap was measured with speaker separations of 15, 22.5, 45, and 90 degrees . Asymptotic level and the growth rate of PPI increased with increased separation from 15 to 90 degrees , but even the 15 degrees SSwap provided significant PPI for the mean performance of the group. SSwap in Experiment 3 used octave band noise (2-4, 4-8, 8-16, or 16-32 kHz) and separations of 7.5 to 180 degrees . SSwap was most effective for the highest frequencies, with no significant PPI for SSwap below 8-16 kHz, or for separations of 7.5 degrees . In Experiment 4 SSwap had WBN sound levels from 40 to 78 dB SPL, and separations of 22.5, 45, 90, and 180 degrees : PPI increased with level, this effect varying with ISI and angular separation. These experiments extend the prior findings on sound localization in mice, and the dependence of PPI on ISI adds a reaction time-like dimension to this behavioral analysis. PMID- 20364889 TI - Role of corticosterone in trace and delay conditioned fear-potentiated startle in rats. AB - Emotional events often lead to particularly strong memory formation. Corticosterone, the final product of hypothalamic-pituitary-adrenal (HPA)-axis activation, has been suggested to play a critical role in this effect. Although a great deal of work has implicated the amygdala as a necessary structure for the effects of corticosterone, other studies have suggested a critical role for the hippocampus in determining the involvement of corticosterone. The current experiments examined this question by disrupting corticosterone synthesis with administration of metyrapone (25 or 100 mg/kg) prior to training in either dorsal hippocampus-independent delay fear conditioning or dorsal hippocampus-dependent trace fear conditioning. Metyrapone administration 2 hrs prior to training significantly attenuated corticosterone secretion during training, but these effects were transient as corticosterone levels were similar to control subjects following the test session. As hypothesized, only trace fear conditioning was impaired. This suggests that only fear conditioning tasks that are dependent on the dorsal hippocampus require HPA-axis activation in order to be learned. PMID- 20364890 TI - Is sexual motivational state linked to dopamine release in the medial preoptic area? AB - The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we asked whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail (Coturnix japonica), a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intermittent organ, resulting in a very different topography of their sexual response. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, during, and after exposure to a female using in vivo microdialysis and analyzed using high-performance liquid chromatography with electrochemical detection. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female. However, quail that failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Furthermore, in quail that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only to copulatory behavior or physical arousal. PMID- 20364891 TI - Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats. AB - The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia. PMID- 20364892 TI - Visual marking and facial affect: can an emotional face be ignored? AB - Previewing a set of distractors allows them to be ignored in a subsequent visual search task (Watson & Humphreys, 1997). Seven experiments investigated whether this preview benefit can be obtained with emotional faces, and whether negative and positive facial expressions differ in the extent to which they can be ignored. Experiments 1-5 examined the preview benefit with neutral, negative, and positive previewed faces. These results showed that a partial preview benefit occurs with face stimuli, but that the valence of the previewed faces has little impact. Experiments 6 and 7 examined the time course of the preview benefit with valenced faces. These showed that negative faces were more difficult to ignore than positive faces, but only at short preview durations. Furthermore, a full preview benefit was not obtained with face stimuli even when the preview duration was extended up to 3 s. The findings are discussed in terms of the processes underlying the preview benefit, their ecological sensitivity, and the role of emotional valence in attentional capture and guidance. PMID- 20364893 TI - Disgust selectively modulates reciprocal fairness in economic interactions. AB - We report two studies aimed at investigating the effects of distinct negative emotions on pairwise economic interactions. In the ultimatum game, a proposer offers a division of a sum of money to a responder who decides whether to accept the split, or reject and leave both players with nothing. In Experiment 1, we investigated whether induced disgust, as compared to sadness and neutral emotion, specifically influences responders' decisions to reject unfair proposals. In Experiment 2, we assessed whether the effects of disgust were selectively related to social contexts by contrasting interactions with a human partner with those involving a computer. Results showed that relative to being in a sad or neutral mood, induced feelings of disgust significantly increased rejection rates of unfair offers. Moreover, we found that when the partner was not responsible for the fairness violation, such as in the computer-offer condition, the disgust induction failed to affect participants' choices. We conclude by focusing on the hypothesis that disgust and social norm violations may share common computational components, both at a psychological and a neural level. PMID- 20364894 TI - Associative and spontaneous appraisal processes independently contribute to anger elicitation in daily life. AB - There has been a great deal of debate concerning the antecedents of anger, with appraisal theorists emphasizing the role of hostile interpretations and cognitive neo-associationistic theorists emphasizing the role of more basic associative processes. Recently, theorists have sought to reconcile these views by acknowledging the role of both associative and inferential processes, and the current investigation drew upon recent social-cognitive research to test this compromise. Individual differences in hostile inferences and associations were assessed in an implicit cognitive paradigm, and relevant outcomes were assessed in a daily diary protocol. Implicit hostile inferences predicted both anger and aggression in daily life, and such relationships were mediated by propensities toward hostile interpretations in daily life. Hostile associations also predicted anger in daily life, but this relationship proved to be independent of daily hostile interpretations. Results therefore support a model that acknowledges the role of both associative and appraisal processes in anger elicitation. PMID- 20364895 TI - Influence of different positive emotions on persuasion processing: a functional evolutionary approach. AB - Much research has found that positive affect facilitates increased reliance on heuristics in cognition. However, theories proposing distinct evolutionary fitness-enhancing functions for specific positive emotions also predict important differences among the consequences of different positive emotion states. Two experiments investigated how six positive emotions influenced the processing of persuasive messages. Using different methods to induce emotions and assess processing, we showed that the positive emotions of anticipatory enthusiasm, amusement, and attachment love tended to facilitate greater acceptance of weak persuasive messages (consistent with previous research), whereas the positive emotions of awe and nurturant love reduced persuasion by weak messages. In addition, a series of mediation analyses suggested that the effects distinguishing different positive emotions from a neutral control condition were best accounted for by different mediators rather than by one common mediator. These findings build upon approaches that link affective valence to certain types of processing, documenting emotion-specific effects on cognition that are consistent with functional evolutionary accounts of discrete positive emotions. PMID- 20364896 TI - Emotion-attention interactions in recognition memory for distractor faces. AB - Effective filtering of distractor information has been shown to be dependent on perceptual load. Given the salience of emotional information and the presence of emotion-attention interactions, we wanted to explore the recognition memory for emotional distractors especially as a function of focused attention and distributed attention by manipulating load and the spatial spread of attention. We performed two experiments to study emotion-attention interactions by measuring recognition memory performance for distractor neutral and emotional faces. Participants performed a color discrimination task (low-load) or letter identification task (high-load) with a letter string display in Experiment 1 and a high-load letter identification task with letters presented in a circular array in Experiment 2. The stimuli were presented against a distractor face background. The recognition memory results show that happy faces were recognized better than sad faces under conditions of less focused or distributed attention. When attention is more spatially focused, sad faces were recognized better than happy faces. The study provides evidence for emotion-attention interactions in which specific emotional information like sad or happy is associated with focused or distributed attention respectively. Distractor processing with emotional information also has implications for theories of attention. PMID- 20364898 TI - Embodied auditory perception: the emotional impact of approaching and receding sound sources. AB - Research has shown the existence of perceptual and neural bias toward sounds perceived as sources approaching versus receding a listener. It has been suggested that a greater biological salience of approaching auditory sources may account for these effects. In addition, these effects may hold only for those sources critical for our survival. In the present study, we bring support to these hypotheses by quantifying the emotional responses to different sounds with changing intensity patterns. In 2 experiments, participants were exposed to artificial and natural sounds simulating approaching or receding sources. The auditory-induced emotional effect was reflected in the performance of participants in an emotion-related behavioral task, their self-reported emotional experience, and their physiology (electrodermal activity and facial electromyography). The results of this study suggest that approaching unpleasant sound sources evoke more intense emotional responses in listeners than receding ones, whereas such an effect of perceived sound motion does not exist for pleasant or neutral sound sources. The emotional significance attributed to the sound source itself, the loudness of the sound, and loudness change duration seem to be relevant factors in this disparity. PMID- 20364899 TI - Attentional retraining procedures: manipulating early or late components of attentional bias? AB - According to cognitive models of anxiety disorders, attentional bias for threatening information is a vulnerability factor to the etiology and maintenance of anxiety. A recently developed methodology to reduce attentional bias has been found to reduce emotional reactivity and anxiety. The present study aimed at identifying the effects of this attentional bias reduction on early and later stages of threat processing. Undergraduates were allocated to an attentional bias reduction (n = 23) versus control condition (n = 25). It was found that attentional bias reduction influenced late but not early stages of threat processing. This finding is of theoretical importance in relation to studies on the causal role of attentional bias and emotional reactivity. Moreover, the present findings also bear relevance to the clinical application of attentional retraining procedures. PMID- 20364900 TI - A longitudinal investigation of the affective environment in families with young children: from infancy to early school age. AB - We examined the affective environment in 102 families studied longitudinally when children were 7, 15, 25, 38, 52, and 67 months of age. At each assessment, every mother-child and father-child dyad was observed in typical daily contexts. Each person's emotions of affection, joy, and anger were coded. Both parents rated marital satisfaction when children were 15, 52, and 67 months. Growth curve analyses, using Actor-Partner Interdependence Modeling, examined (a) developmental changes in emotions, (b) within-relationship influences of the partner's emotions, (c) across-relationship influences of emotions in other parent's interactions with the child, and (d) associations between marital quality and emotions over time. Parents' emotional expressiveness was highest early in the child's development, and declined thereafter. Children's anger was highest at 15 months of age, and declined thereafter, and their positive emotions, particularly with mothers, increased over time. Generally, one's positive emotions and better marital quality were associated with greater positive emotion within- and across-relationships, whereas one's anger was associated with greater anger within- and across-relationships. However, any emotion expression elicited greater affection in the interaction partner. Parents' neuroticism did not account for the convergence of emotions across relationships. PMID- 20364901 TI - Blind jealousy? Romantic insecurity increases emotion-induced failures of visual perception. AB - Does the influence of close relationships pervade so deeply as to impact visual awareness? Results from two experiments involving heterosexual romantic couples suggest that they do. Female partners from each couple performed a rapid detection task where negative emotional distractors typically disrupt visual awareness of subsequent targets; at the same time, their male partners rated attractiveness first of landscapes, then of photos of other women. At the end of both experiments, the degree to which female partners indicated uneasiness about their male partner looking at and rating other women correlated significantly with the degree to which negative emotional distractors had disrupted their target perception during that time. This relationship was robust even when controlling for individual differences in baseline performance. Thus, emotions elicited by social contexts appear to wield power even at the level of perceptual processing. PMID- 20364902 TI - Emotion regulation and decision making under risk and uncertainty. AB - It is well established that emotion plays a key role in human social and economic decision making. The recent literature on emotion regulation (ER), however, highlights that humans typically make efforts to control emotion experiences. This leaves open the possibility that decision effects previously attributed to acute emotion may be a consequence of acute ER strategies such as cognitive reappraisal and expressive suppression. In Study 1, we manipulated ER of laboratory-induced fear and disgust, and found that the cognitive reappraisal of these negative emotions promotes risky decisions (reduces risk aversion) in the Balloon Analogue Risk Task and is associated with increased performance in the prehunch/hunch period of the Iowa Gambling Task. In Study 2, we found that naturally occurring negative emotions also increase risk aversion in Balloon Analogue Risk Task, but the incidental use of cognitive reappraisal of emotions impedes this effect. We offer evidence that the increased effectiveness of cognitive reappraisal in reducing the experience of emotions underlies its beneficial effects on decision making. PMID- 20364903 TI - The voluntary control of facial action units in adults. AB - We investigated adults' voluntary control of 20 facial action units theoretically associated with 6 basic emotions (happiness, fear, anger, surprise, sadness, and disgust). Twenty young adults were shown video excerpts of facial action units and asked to reproduce them as accurately as possible. Facial Action Coding System (FACS; Ekman & Friesen, 1978a) coding of the facial productions showed that young adults succeeded in activating 18 of the 20 target actions units, although they often coactivated other action units. Voluntary control was clearly better for some action units than for others, with a pattern of differences between action units consistent with previous work in children and adolescents. PMID- 20364904 TI - Inhibition of return to negative emotion: evidence from an emotional expression detection task. AB - After the presentation of an uninformative spatial cue, it usually takes participants more time to respond to a target that appears at the cued location when the interval between the cue and target is long. This phenomenon is named inhibition of return (IOR), implying that returning attention to the cued location is inhibited because of attentional disengagement. The present study investigated whether irrelevant emotional information is processed by the attentional system in a similar manner. Uninformative positive and negative emotional cues were presented at the center of the screen, and faces were presented as the target. An emotional expression detection task was used to reveal the inhibitory and facilitatory aftereffects of the attentional processing of the emotional cues. An emotion-based IOR effect on reaction time was observed only after the presence of a negative emotional cue, implying that the attentional system tends to inhibit irrelevant negative emotion but not inhibit irrelevant positive emotion. PMID- 20364905 TI - Gaze direction modulates the disengagement of attention from facial expression in 10-month-olds. AB - This study investigated whether the disengagement of attention from facial expression is modulated by gaze direction in infants. To this end, we measured the saccadic reaction time required for the 10-month-olds to disengage their attention from angry and happy expressions combined with either straight or averted gaze. The 10-month-olds' disengagement of their attention from happy faces was modulated by gaze direction. This finding indicates that gaze direction strongly influences infants' allocation of attention to facial expressions. PMID- 20364906 TI - Emotional modulation of the attentional blink: is there an effect of stress? AB - Individuals are often unable to identify the second target (T2) of two when it is presented within 500 ms after the first target (T1). This "attentional blink" (AB) is attenuated by an emotionally arousing T2. Stress is known to affect cognitive performance, in particular for emotional material. In the present study, we asked whether (a) an emotional T2 reduces the AB when preceded by an emotional T1 and (b) the emotional modulation of the AB is affected by stress. Participants were presented neutral and aversive words as T1 and T2 in rapid serial visual presentation after they were exposed to stress (socially evaluated cold pressor test) or a control condition in a crossover manner. Our results indicate that an aversive T1 extends the AB. Aversive T2 attenuated the AB in the presence of a neutral, but not an aversive, T1. Stress-enhanced T2 detection and high cortisol responses to stress reduced the AB. However, neither stress nor cortisol interacted with the emotionality of the target words. In summary, these findings point to a strong impact of emotional factors on early perceptual experiences. PMID- 20364907 TI - Gratitude as moral sentiment: emotion-guided cooperation in economic exchange. AB - Economic exchange often pits options for selfish and cooperative benefit against one another. Decisions favoring communal profit at the expense of self-interest have traditionally been thought to stem from strategic control aimed at tamping down emotional responses centered on immediate resource acquisition. In the present article, evidence is provided to argue against this limited view of the role played by emotion in shaping prosociality. Findings demonstrate that the social emotion gratitude functions to engender cooperative economic exchange even at the expense of greater individual financial gains. Using real-time inductions, increased gratitude is shown to directly mediate increased monetary giving within the context of an economic game, even where such giving increases communal profit at the expense of individual gains. Moreover, increased giving occurred regardless of whether the beneficiary was a known individual or complete stranger, thereby removing the possibility that it stemmed from simple awareness of reciprocity constraints. PMID- 20364908 TI - The memory enhancement effect of emotion is absent in conceptual implicit memory. AB - Memory for emotional stimuli is superior to memory for neutral stimuli. This study investigated whether this memory advantage is present in implicit memory. Memory was tested with a test of explicit memory (associate cued recall) and a test of conceptual implicit memory (free association) identical in all respects apart from the retrieval instructions. After studying emotional and neutral paired associates, participants saw the first member of the pair, the cue; in the test of explicit memory participants were instructed to recall the associate; in the test of implicit memory participants were instructed to generate the first word coming to mind associated to the word. Depth of study processing dissociated performance in the tests, confirming that the free-association test was not contaminated by an intentional retrieval strategy. Emotional pairs were better recalled than neutral pairs in the test of explicit memory but not in the equivalent test of implicit memory. The absence of an emotion effect in implicit memory implies that emotional material does not have a privileged global mnemonic status; intentional retrieval is necessary for observing the emotion-related memory advantage. PMID- 20364909 TI - How does service workers' behavior affect their health? Service climate as a moderator in the service behavior-health relationships. AB - To address the question of whether providing high-quality service deteriorates or benefits workers' health, a contingency model was tested that focused on service climate as a moderator. This interacts with service behavior to affect workers' perceptions of emotional exhaustion, hence their physical and mental health. Findings of this study with 328 nurses from 66 nursing units indicated that congruent conditions of service climate and behaviors benefited workers' health, whereas incongruent conditions affected it adversely. The findings are discussed in light of stress, and emotion-work perspectives. PMID- 20364911 TI - Regulating strain states by using the recovery potential of lunch breaks. AB - The aim of the worksite study is to elucidate the strain reducing impact of different forms of spending lunch breaks. With the help of the so-called silent room cabin concept, it was possible to induce a lunch-break relaxation opportunity that provided visual and territorial privacy. To evaluate the proposed effects, 14 call center agents were assigned to either 20 min progressive muscle relaxation (PMR) or small-talk (ST) break groups. We analyzed the data in a controlled trial for a period of 6 months (every 2 months four measurements a day at 12:00, 13:00, 16:00, 20:00) using independent observer and self-report ratings of emotional, mental, motivational, and physical strain. Results indicated that only the PMR break reduced postlunchtime and afternoon strain. Although further intervention research is required, our results suggest that PMR lunch break may sustainable reduce strain states in real worksite settings. PMID- 20364910 TI - Mood, blood pressure, and heart rate at work: an experience-sampling study. AB - We describe a study that examined the distinctiveness of momentary positive and negative affect (PA and NA) and their relationships with blood pressure and heart rate at work in a sample of 67 full-time employees who provided psychological and physiological measurements multiple times a day, over 10 working days. These employees recorded their subjective ratings on personal digital assistant devices programmed specifically for this study, and assessed their blood pressure and heart rate using automatic recording devices, at each measurement period. Results support the distinctiveness of PA and NA. First, within-individual factor analyses confirmed the existence of two underlying factors in the momentary affect ratings. Second, the within-individual correlations between PA and NA scores (-.14), and among the two latent constructs (-.13) were both low in magnitude. Finally, as predicted by theory, NA was significantly related to blood pressure within individuals, whereas PA and blood pressure were unrelated (both PA and NA were related to heart rate within individuals, as predicted). PMID- 20364912 TI - Do the weary care about racioethnic similarity? The role of emotional exhaustion in relational demography. AB - Diversity theorists have hypothesized that similarity leads to both greater identification among individuals and reduced interpersonal conflict within organizations. Little research, however, has been conducted to identify boundary conditions for this relationship. The authors investigated the interactive effects of supervisor-subordinate racioethnic similarity and emotional exhaustion on organizational commitment in two studies. In Study 1, racioethnic supervisor subordinate similarity related positively to commitment, but only among employees low in emotional exhaustion. In Study 2, we observed a significant indirect effect of racioethnic similarity on loyalty through supervisor support. Moreover, the support-loyalty linkage was significantly stronger for employees low in emotional exhaustion. Thus, the effects of supervisor-subordinate racioethnic similarity on employee commitment appear contingent upon employee emotional exhaustion. PMID- 20364913 TI - Can counterproductive work behaviors be productive? CWB as emotion-focused coping. AB - The goal of our study was to determine whether some forms of counterproductive work behavior (CWB) may serve to benefit employees. Building on the stressor strain framework and theories of coping, we investigated whether two forms of CWB, production deviance and withdrawal, serve as a means of coping to mitigate the impact of low distributive and procedural justice on emotional exhaustion. Results from a survey of 295 employed persons from around the United States suggest that production deviance and withdrawal may benefit employees by reducing emotional exhaustion in the face of low distributive justice but not necessarily low procedural justice. PMID- 20364914 TI - Stress among managers: the importance of dynamic tasks, predictability, and social support in unpredictable times. AB - In this field study, we examined the importance of dynamic tasks as stressors faced by managers. Predictability of a task and social support by managers' supervisors were considered as potential moderators of the interrelation between stressors and stress effects. A total of 142 managers (64 women, 78 men) from 46 German companies took part in our study. As expected, the more tasks were perceived as dynamic, the higher was the irritation level. This correlation was significant, but low as could be expected when choosing a single predictor to explain the level of irritation. Dynamic tasks and predictability were unrelated features of the work task. Predictability of a task had a moderating effect in that the interrelation between dynamic tasks and irritation was stronger when predictability was low. When managers perceived low support from their supervisors, the interrelation between dynamic tasks and irritation was stronger as well. We were able to evaluate the specific demands of managers in a rapidly changing environment. Our results demonstrated that dynamic tasks do not necessarily lead to impaired health. Managers' supervisors can play an important role by reflecting on how to impose change for the managers. PMID- 20364915 TI - Predicting flow at work: investigating the activities and job characteristics that predict flow states at work. AB - Flow (a state of consciousness where people become totally immersed in an activity and enjoy it intensely) has been identified as a desirable state with positive effects for employee well-being and innovation at work. Flow has been studied using both questionnaires and Experience Sampling Method (ESM). In this study, we used a newly developed 9-item flow scale in an ESM study combined with a questionnaire to examine the predictors of flow at two levels: the activities (brainstorming, planning, problem solving and evaluation) associated with transient flow states and the more stable job characteristics (role clarity, influence and cognitive demands). Participants were 58 line managers from two companies in Denmark; a private accountancy firm and a public elder care organization. We found that line managers in elder care experienced flow more often than accountancy line managers, and activities such as planning, problem solving, and evaluation predicted transient flow states. The more stable job characteristics included in this study were not, however, found to predict flow at work. PMID- 20364916 TI - A multilevel model of the effects of equal opportunity climate on job satisfaction in the military. AB - To date, minimal work has explored associations between equal opportunity (EO) climate and employee work attitudes, and no known research has investigated the effects of EO climate beyond the individual level. We address these gaps in the literature by testing a multilevel structural equation model in which effects of EO climate are considered at both the individual and unit levels. At the individual level, we predicted that psychological EO climate would be directly associated with job stress and job satisfaction, as well as indirectly related to job satisfaction via stress. In addition, cross-level associations between unit EO climate and job stress and job satisfaction were hypothesized to be mediated by cohesion. Findings supported the proposed model; hypothesized relations were supported at both levels of analysis. We conclude with a discussion of the findings, study limitations, and directions for future EO climate research. PMID- 20364917 TI - The mechanisms of involuntary attention. AB - We tested 3 mechanisms of involuntary attention: (1) a perceptual enhancement mechanism, (2) a response-decision mechanism, and (3) a serial-search mechanism. Experiment 1 used a response deadline technique to compare the perceptual enhancement and the decision mechanisms and found evidence consistent with the decision mechanism. Experiment 2 used a multiple-targets paradigm to compare the decision and serial-search mechanisms. The results favored the decision mechanism. Experiment 3, which varied the display size and whether distractors were present in the display, found that when locating the target was easy, the results conformed to the decision mechanism. However, when locating the target was difficult, the serial-search mechanism was favored. Thus, there appears to be at least 2 mechanisms of involuntary attention. The serial-search mechanism accounts for involuntary attention when the target is difficult to locate, whereas the decision mechanism accounts for results when the target is easy to locate. PMID- 20364918 TI - Early and late selection in unconscious information processing. AB - In four experiments, we investigated whether masked stimuli in priming experiments are subjected to early or to late selection. In Experiment 1, participants classified four target-pictures as being small or large. In line with early selection accounts, prime-pictures with a different perceptual appearance as the experienced targets did not elicit congruency effect. In Experiment 2, 40 targets all depicting animals were presented. Results were in line with late selections assumptions because novel animal primes but not novel primes from different semantic categories yielded congruency effects. In Experiment 3, the targets were chosen such that there is a second semantic feature that covaried with the required response. Here, novel primes picturing small animals did not influence target responses with regard to the instructed size classification, but with regard to their affiliation to the category animal. In Experiment 4, small and large pictures from two categories were presented. Category match did not influence priming, ruling out that feature overlap contaminated the former results. The results indicate that participants' prestimulus expectations determine in which stage in the processing-stream masked stimuli are selected. PMID- 20364919 TI - Salience is only briefly represented: evidence from probe-detection performance. AB - Salient objects in the visual field tend to capture attention. The present study aimed to examine the time-course of salience effects using a probe-detection task. Eight experiments investigated how the salience of different orientation singletons affected probe reaction time as a function of stimulus onset asynchrony (SOA) between the presentation of a singleton display and a probe display. The results demonstrate that salience consistently affected probe reaction time at the shortest SOA. The effect of salience disappeared as SOA increased. These results suggest that contrary to the assumption of major theories on visual selection, salience is transiently represented in our visual system allowing the effects of salience on attentional selection to be only short lived. PMID- 20364920 TI - Top-down attentional control for distractor locations: the benefit of precuing distractor locations on target localization and discrimination. AB - This study investigated the active inhibition of precued distractor locations. In this study, the distractor location was precued by an arrow. Experiment 1 indicated that a valid precue could facilitate target localization. Experiment 2 demonstrated that when conflict trials were included, the distractor precue benefit was eliminated. Experiment 3 further showed that active inhibition required time to operate. The distractor precue benefit was observed only when the stimulus onset asynchrony between the precue and the target and distractor display was long. Experiment 4 illustrated that the benefit was not contingent on precuing the distractor response. Experiment 5 indicated that the benefit of distractor precuing was not due to the activation of target locations, and Experiment 6 showed that this benefit was due to attentional inhibition. Finally, Experiment 7 demonstrated that active inhibition of spatial location required an attentional resource to operate. These results indicated how a top-down mechanism exerted control on distractor locations. PMID- 20364921 TI - Stimulus-driven attentional capture by a static discontinuity between perceptual groups. AB - After C. L. Folk, R. W. Remington, and J. C. Johnston (1992) proposed their contingent-orienting hypothesis, there has been an ongoing debate over whether purely stimulus-driven attentional capture can occur for visual events that are salient by virtue of a distinctive static property (as opposed to a dynamic property such as abrupt onset). The present study identified 3 methodological criteria for establishing that attentional capture is stimulus driven and not contingent on top-down attentional control settings. In 5 experiments, attentional capture occurred for a static discontinuity at the boundary between one group of homogeneous items (red Xs) abutted next to a group of homogeneous items that were featurally different (green Xs) within a single row. Experiment 1 intentionally violated one of the criteria for demonstrating stimulus-driven capture so as to establish that contingent attentional capture can occur for this novel type of static cue. In the remaining 4 experiments, even with all 3 criteria for stimulus-driven capture partially or completely satisfied, the static discontinuity captured attention. These attentional capture effects are the first to be obtained when all 3 criteria for establishing that they are purely stimulus driven have been satisfied. PMID- 20364922 TI - Context effects on the processing of action-relevant object features. AB - In 4 experiments, we investigated the effects of object affordance in reach-to grasp actions. Participants indicated whether a depicted small or large object was natural or manmade by means of different object-grasping responses (i.e., with a power or a precision grip). We observed that the size of the depicted object affected the grasping kinematics (grip aperture) and the reach-onset times of compatible and incompatible actions. Additional experiments showed that the effect of perceived object size on motor response was modulated by contextual action information and the observation of others' actions with the object. Thus, beyond the observation of object affordance effects in natural grasping actions, this study suggests that the coupling between object perception and action is not static and obligatory. Behavioral effects of action-relevant object features seem rather to depend on contextual action information. PMID- 20364923 TI - Grasping beer mugs: on the dynamics of alignment effects induced by handled objects. AB - We examined automatic spatial alignment effects evoked by handled objects. Using color as the relevant cue carried by an irrelevant handled object aligned or misaligned with the response hand, responses to color were faster when the handle aligned with the response hand. Alignment effects were observed only when the task was to make a reach and grasp response. No alignment effects occurred if the response involved a left-right key press. Alignment effects emerged over time, becoming more apparent either when the color cue was delayed or when relatively long, rather than short, response times were analyzed. These results are consistent with neurophysiological evidence indicating that the cued goal state has a modulatory influence on sensorimotor representations, and that handled objects initially generate competition between neural populations coding for a left- or right-handed action that must be resolved before a particular hand is favored. PMID- 20364924 TI - Embodied rules in tool use: a tool-switching study. AB - In tool use, a transformation rule defines the relation between an operating movement and its distal effect. This rule is determined by the tool structure and requires no explicit definition. The present study investigates how humans represent and apply compatible and incompatible transformation rules in tool use. In Experiment 1, participants had to switch between tools for which the respective transformation rules were either the same or different. This way, rule repetitions could be dissociated from tool repetitions. In Experiment 2, the application of transformation rules in tool use was compared with the application of explicitly defined rules. In Experiment 3, actions of tool use were cued either by tool pictures or by written tool names. The results suggest that a transformation rule in tool use has a cognitive representation that is independent of the concrete tool incorporating it. Furthermore, its application differs from the application of an explicitly defined rule in terms of reduced top-down processing. PMID- 20364925 TI - Sufficiency of longitudinal moment of inertia for haptic cylinder length judgments. AB - Many studies invoke moment of inertia (Iii) as necessary and sufficient information to perceive cylinder length via wielding, yet some assert that Iii is neither necessary (weight, m, or static moment, M, are sufficient) nor sufficient for length judgments (m or M is necessary). Mathematical expressions for Iii not involving m or M imply length, so Iii could be sufficient for cylinder length judgments. In 5 experiments (N = 113), only longitudinal Iii (the smallest principal value) informed cylinder length estimates in a novel task, rolling. Experiment 1 yielded reliable length judgments. Varying diameter supported length scaling (Experiment 2); similar length estimates occurred with both rolling and wielding (Experiment 3); feedback improved rolling length judgments to levels commensurate with wielding (Experiment 4); and length judgments shifted predictably with added mass (Experiment 5). Contrary to proposals in the literature, Iii is sufficient information for cylinder length judgments, absent m or M information, even when Iii is of minimal magnitude and the task quite novel. PMID- 20364926 TI - Modularity beyond perception: evidence from the PRP paradigm. AB - The Dimension Action (DA) model asserts that the visual system is modular, and that each task involves multiple-response mechanisms rather than a unitary response selection mechanism. The model has been supported by evidence from single-task interference paradigms. We use the psychological refractory period paradigm and show that dual-task performance can also be explained by the DA model. In 6 experiments we contrasted predictions from the DA model with predictions from the Response Selection Bottleneck (RSB; Pashler, 1994) model asserting that dual-task limitations are due to a unitary-response selection mechanism. Task 1 in all experiments was a tone discrimination task. In Experiments 1 to 3, Task 2 was a variation of either the Stroop or the flanker tasks. Experiments 4 to 6 manipulated response selection directly. The results showed that response selection effects can be underadditive in some conditions and additive in others depending on the modular nature of the response effect. Together, the results support the existence of an underlying modular architecture as proposed by the DA model and pose serious difficulties for the RSB model. PMID- 20364927 TI - The impact of intervening tasks on response preparation. AB - Response preparation usually facilitates performance, but it may also interfere with other concurrent tasks. In this article, the authors used event-related brain potentials to study how intervening tasks affect response preparation. In 3 experiments, participants performed intervening tasks during the preparation of a precued hand choice response. Intervening tasks were simple or choice foot responses to tones with different probabilities or at different times during the preparation period. The contingent negative variation component indicated that the intervening task led to an increased recruitment of processing resources, whereas behavioral data and the lateralized readiness potential indicated a deliberately reduced level of preparedness. Two factors seem to be responsible for this result pattern, a bottleneck-like postponement of the prepared response and a reluctance of participants to prepare prior to expected interference. PMID- 20364928 TI - Motivational influences on response inhibition measures. AB - Psychological research has placed great emphasis on inhibitory control due to its integral role in normal cognition and clinical disorders. The stop-signal task and associated measure--stop-signal reaction time (SSRT)--provides a well established paradigm for measuring response inhibition. However, motivational influences on stop-signal performance and SSRT have not been examined. We conceptualize the stop-signal paradigm as a decision-making task involving the trade-off between fast responding and accurate inhibition. In 4 experiments, we demonstrate that performance trade-offs are influenced by inherent motivational biases and explicit strategic control. As a result, SSRT was lower when participants favored correct stopping over fast responding than when the same participants favored fast responding over correct stopping. We present a novel variant of the stop-signal task that uses monetary incentives to manipulate motivated speed-accuracy trade-offs. By sampling performance at multiple-trade off settings, we obtain a measure of inhibitory ability that is independent of trade-off bias, and thus, more easily interpretable when comparing across participants. We present a working theoretical model to explain the effects of motivational context on response inhibition. PMID- 20364929 TI - Selective interference on the holistic processing of faces in working memory. AB - Faces and objects of expertise compete for early perceptual processes and holistic processing resources (Gauthier, Curran, Curby, & Collins, 2003). Here, we examined the nature of interference on holistic face processing in working memory by comparing how various types of loads affect selective attention to parts of face composites. In dual tasks, all loads impaired overall performance on face judgment compared with no load. However, a face load reduced holistic face processing (Experiment 1) whereas an object load did not, regardless of expertise (Experiments 2 and 3). Also, 2 types of faces produced asymmetrical interference on each other (Experiment 4), refuting the hypothesis that any faces would produce equal interference. Thus, the interference on holistic face processing in working memory does not depend on overlap in expertise or face processing, but may be modulated by limitations in encoding or maintenance of highly similar representations. PMID- 20364930 TI - Integration of acoustical information in the perception of impacted sound sources: the role of information accuracy and exploitability. AB - Sound sources are perceived by integrating information from multiple acoustical features. The factors influencing the integration of information are largely unknown. We measured how the perceptual weighting of different features varies with the accuracy of information and with a listener's ability to exploit it. Participants judged the hardness of two objects whose interaction generates an impact sound: a hammer and a sounding object. In a first discrimination experiment, trained listeners focused on the most accurate information, although with greater difficulty when perceiving the hammer. We inferred a limited exploitability for the most accurate hammer-hardness information. In a second rating experiment, listeners focused on the most accurate information only when estimating sounding-object hardness. In a third rating experiment, we synthesized sounds by independently manipulating source properties that covaried in Experiments 1 and 2: sounding-object hardness and impact properties. Sounding object hardness perception relied on the most accurate acoustical information, whereas impact-properties influenced more strongly hammer hardness perception. Overall, perceptual weight increased with the accuracy of acoustical information, although information that was not easily exploited was perceptually secondary, even if accurate. PMID- 20364931 TI - Testing for lexical competition during reading: fast priming with orthographic neighbors. AB - Recent studies have found that masked word primes that are orthographic neighbors of the target inhibit lexical decision latencies (Davis & Lupker, 2006; Nakayama, Sears, & Lupker, 2008), consistent with the predictions of lexical competition models of visual word identification (e.g., Grainger & Jacobs, 1996). In contrast, using the fast priming paradigm (Sereno & Rayner, 1992), orthographically similar primes produced facilitation in a reading task (H. Lee, Rayner, & Pollatsek, 1999; Y. Lee, Binder, Kim, Pollatsek, & Rayner, 1999). Experiment 1 replicated this facilitation effect using orthographic neighbor primes. In Experiment 2, neighbor primes and targets were presented in different cases (e.g., SIDE-tide); in this situation, the facilitation effect disappeared. However, nonword neighbor primes (e.g., KIDE-tide) still significantly facilitated reading of targets (Experiment 3). Taken together, these results suggest that it is possible to explain the priming effects from word neighbor primes in fast priming experiments in terms of the interactions between the inhibitory and facilitory processes embodied in lexical competition models. PMID- 20364932 TI - A test of motor (not executive) planning in developmental coordination disorder and autism. AB - Grip selection tasks have been used to test "planning" in both autism and developmental coordination disorder (DCD). We differentiate between motor and executive planning and present a modified motor planning task. Participants grasped a cylinder in 1 of 2 orientations before turning it clockwise or anticlockwise. The rotation resulted in a comfortable final posture at the cost of a harder initial reaching action on 50% of trials. We hypothesized that grip selection would be dominated by motoric developmental status. Adults were always biased towards a comfortable end-state with their dominant hand, but occasionally ended uncomfortably with their nondominant hand. Most 9- to 14-year-olds with and without autism also showed this "end-state comfort" bias but only 50% of 5- to 8 year-olds. In contrast, children with DCD were biased towards selecting the simplest initial movement. Our results are best understood in terms of motor planning, with selection of an easier initial grip resulting from poor reach-to grasp control rather than an executive planning deficit. The absence of differences between autism and controls may reflect the low demand this particular task places on executive planning. PMID- 20364933 TI - The impact of facial emotional expressions on behavioral tendencies in women and men. AB - Emotional faces communicate both the emotional state and behavioral intentions of an individual. They also activate behavioral tendencies in the perceiver, namely approach or avoidance. Here, we compared more automatic motor to more conscious rating responses to happy, sad, angry, and disgusted faces in a healthy student sample. Happiness was associated with approach and anger with avoidance. However, behavioral tendencies in response to sadness and disgust were more complex. Sadness produced automatic approach but conscious withdrawal, probably influenced by interpersonal relations or personality. Disgust elicited withdrawal in the rating task, whereas no significant tendency emerged in the joystick task, probably driven by expression style. Based on our results, it is highly relevant to further explore actual reactions to emotional expressions and to differentiate between automatic and controlled processes because emotional faces are used in various kinds of studies. Moreover, our results highlight the importance of gender of poser effects when applying emotional expressions as stimuli. PMID- 20364934 TI - Auditory imagery shapes movement timing and kinematics: evidence from a musical task. AB - The role of anticipatory auditory imagery in music-like sequential action was investigated by examining timing accuracy and kinematics using a motion capture system. Musicians responded to metronomic pacing signals by producing three unpaced taps on three vertically aligned keys at the given tempo. Taps triggered tones in two out of three blocked feedback conditions, where key-to-tone mappings were compatible or incompatible in terms of spatial and pitch height. Results indicate that, while timing was most accurate without tones, movements were smaller in amplitude and less forceful (i.e., acceleration prior to impact was lowest) when tones were present. Moreover, timing was more accurate and movements were less forceful with compatible than with incompatible auditory feedback. Observing these effects at the first tap (before tone onset) suggests that anticipatory auditory imagery modulates the temporal kinematics of regularly timed auditory action sequences, like those found in music. Such cross-modal ideomotor processes may function to facilitate planning efficiency and biomechanical economy in voluntary action. PMID- 20364935 TI - Avalanche dynamics in fluid imbibition near the depinning transition. AB - We study avalanche dynamics and local activity of forced-flow imbibition fronts in disordered media. We focus on the front dynamics as the mean velocity of the interface v is decreased and the pinning state is approached. Scaling arguments allow us to obtain the statistics of avalanche sizes and durations, which become power-law distributed due to the existence of a critical point at v=0 . Results are compared with phase-field numerical simulations. PMID- 20364936 TI - Loewner driving functions for off-critical percolation clusters. AB - We numerically study the Loewner driving function Ut of a site percolation cluster boundary on the triangular lattice for ppc. PMID- 20364937 TI - Nature of the order-disorder transition in the Vicsek model for the collective motion of self-propelled particles. AB - One of the most popular approaches to the study of the collective behavior of self-driven individuals is the well-known Vicsek model (VM) [T. Vicsek, A. Czirok, E. Ben-Jacob, I. Cohen, and O. Shochet, Phys. Rev. Lett. 75, 1226 (1995)]. In the VM one has that each individual tends to adopt the direction of motion of its neighbors with the perturbation of some noise. For low enough noise the individuals move in an ordered fashion with net transport of mass; however, when the noise is increased, one observes disordered motion in a gaslike scenario. The nature of the order-disorder transition, i.e., first-versus second order, has originated an ongoing controversy. Here, we analyze the most used variants of the VM unambiguously establishing those that lead either to first- or second-order behavior. By requesting the invariance of the order of the transition upon rotation of the observational frame, we easily identify artifacts due to the interplay between finite-size and boundary conditions, which had erroneously led some authors to observe first-order transitionlike behavior. PMID- 20364938 TI - Experimental investigation of a Brownian ratchet effect in ferrofluids. AB - We test experimentally a Brownian ratchet system suggested by Engel [Phys. Rev. Lett. 91, 060602 (2003)]. This ratchet system is based on a magnetic fluid that contains nanometer sized magnetic particles in a thermal bath of carrier fluid. An external static magnetic field and, perpendicular to it, an oscillatory magnetic field act on the ferrofluid particles; the total magnetic field contains no rotating component. The directed effective rotation of the particles due to the ratchet effect induces a macroscopic torque density of the fluid. The torque on a spherical ferrofluid sample is measured in dependence on the field parameters. A quantitative comparison with predictions from a microscopic and a phenomenological model are given. Both models describe certain aspects of the measurements correctly, but qualitative discrepancies between both models and experiment are found, particularly in the high-frequency range. PMID- 20364939 TI - Size-dependent nucleation kinetics at nonplanar nanowire growth interfaces. AB - In nanowire growth, kinetic processes at the growth interface can play an important role in governing wire compositions, morphologies, and growth rates. Molecular-dynamics simulations have been undertaken to probe such processes in a system featuring a solid-liquid interface shape characterized by a facet bounded by rough orientations. Simulated growth rates display a dependence on nanowire diameter consistent with a size-dependent barrier for facet nucleation. A theory for the interface mobility is developed, establishing a source for size-dependent growth rates that is an intrinsic feature of systems possessing growth interfaces with faceted and rough orientations. PMID- 20364940 TI - Micropatterning of light-sensitive liquid-crystal elastomers. AB - We demonstrate that photoisomerizable liquid-crystal elastomer soft films can be used as tunable holographic gratings. Optomechanical mechanism of imprinting one dimensional grating structure into the soft matrix by two-beam uv laser interference can be clearly resolved from the time dependence of the reading beam diffraction patterns. We analyze the observed response in terms of cis-trans isomerization-controlled modulation of the grating profile. The grating period can be tuned reversibly by stretching or contraction of the specimen, either thermomechanically or by applying external stress. Temperature-induced modifications of the grating parameters in the vicinity of the nematic paranematic phase transition are also examined. PMID- 20364941 TI - Finite-size analysis of a two-dimensional Ising model within a nonextensive approach. AB - In this work we present a thorough analysis of the phase transitions that occur in a ferromagnetic two-dimensional Ising model, with only nearest-neighbors interactions, in the framework of the Tsallis nonextensive statistics. We performed Monte Carlo simulations on square lattices with linear sizes L ranging from 32 up to 512. The statistical weight of the Metropolis algorithm was changed according to the nonextensive statistics. Discontinuities in the m(T) curve are observed for q< or =0.5 . However, we have verified only one peak on the energy histograms at the critical temperatures, indicating the occurrence of continuous phase transitions. For the 0.5>taucoll but times smaller than the equilibrium time t<>taue , rhoT(yT,t|yT,0) approaches a polynomial-type equilibrium probability density function. Notably, only regimes (A) and (B) are found in the previously considered infinite systems. PMID- 20364945 TI - Microcanonical finite-size scaling in second-order phase transitions with diverging specific heat. AB - A microcanonical finite-size ansatz in terms of quantities measurable in a finite lattice allows extending phenomenological renormalization (the so-called quotients method) to the microcanonical ensemble. The ansatz is tested numerically in two models where the canonical specific heat diverges at criticality, thus implying Fisher renormalization of the critical exponents: the three-dimensional ferromagnetic Ising model and the two-dimensional four-state Potts model (where large logarithmic corrections are known to occur in the canonical ensemble). A recently proposed microcanonical cluster method allows simulating systems as large as L=1024 (Potts) or L=128 (Ising). The quotients method provides accurate determinations of the anomalous dimension, eta, and of the (Fisher-renormalized) thermal nu exponent. While in the Ising model the numerical agreement with our theoretical expectations is very good, in the Potts case, we need to carefully incorporate logarithmic corrections to the microcanonical ansatz in order to rationalize our data. PMID- 20364946 TI - Semiclassical treatment of a Brownian ratchet using the quantum Smoluchowski equation. AB - Quantum effects in the noninertial Brownian motion of a particle in a one dimensional ratchet potential are treated in the high temperature and weak bath particle coupling limit by solving a quantum Smoluchowski equation for the time evolution of the Wigner function in configuration space. In particular, an analytical expression for the stationary average drift velocity for constant driving forces is presented including quantum corrections to any order in Planck's constant. The corresponding frequency response is determined using continued fractions in both the linear approximation holding for small ac driving amplitude and in the nonlinear regime for arbitrary driving amplitude exhibiting pronounced ac induced frequency dependence of the dc component of the average drift velocity. Moreover, Shapiro steps are apparent in the dc characteristics for strong ac driving just as in the dc current-voltage characteristics of a point Josephson junction. PMID- 20364947 TI - Fluctuation relations for diffusion that is thermally driven by a nonstationary bath. AB - In the context of the Markovian dynamical evolution in a nonstationary thermal bath, we construct a family of fluctuation relations for the entropy production that are not verified by the work performed on the system. We exhibit fluctuation relations, which are global versions either of the generalized fluctuation dissipation theorem around a nonequilibrium diffusion or of the usual fluctuation dissipation theorem for energy resulting from a pulse of temperature. PMID- 20364948 TI - Avalanche dynamics of fiber bundle models. AB - We present a detailed analytical and numerical study of the avalanche distributions of the continuous damage fiber bundle model (CDFBM). Linearly elastic fibers undergo a series of partial failure events which give rise to a gradual degradation of their stiffness. We show that the model reproduces a wide range of mechanical behaviors. We find that macroscopic hardening and plastic responses are characterized by avalanche distributions, which exhibit an algebraic decay with exponents between 5/2 and 2 different from those observed in mean-field fiber bundle models. We also derive analytically the phase diagram of a family of CDFBM which covers a large variety of potential avalanche size distributions. Our results provide a unified view of the statistics of breaking avalanches in fiber bundle models. PMID- 20364949 TI - Escape dynamics of coupled particles in nonlinear, disordered lattices. AB - We consider the deterministic escape dynamics of a lattice chain of harmonically coupled particles from a metastable state over a one-dimensional potential barrier. While the case of periodic lattices has already been elaborated, the aim of the present work is to explore the extension to nonperiodic, i.e., disordered, lattices. Each particle evolves in an individual local potential, which is characterized by a harmonic term and a nonlinear term. Two kinds of parametric disorder are considered. "Disorder in nonlinearity" is only caused by different nonlinear terms--"disorder in harmonicity" only by different harmonic terms. We assure that the two kinds of disorder, with their individual potential barriers uniformly distributed around a globally equal mean barrier height, exhibit a comparable strength of disorder. Starting with an initial completely delocalized state, we observe localization of energy and formation of breathers ensues. It is shown that increasing disorder in nonlinearity decreases the mean escape time opposite to increasing mean escape times resulting from increased disorder in harmonicity. Comparison with the mean escape time obtained for a third kind of parametric disorder characterized by overall equal barrier heights leads to the conclusion that indeed inhomogeneous barriers facilitate the speedy escape. PMID- 20364950 TI - Diffusion in the special theory of relativity. AB - The Markovian diffusion theory is generalized within the framework of the special theory of relativity. Since the velocity space in relativity is a hyperboloid, the mathematical stochastic calculus on Riemanian manifolds can be applied but adopted here to the velocity space. A generalized Langevin equation in the fiber space of position, velocity, and orthonormal velocity frames is defined from which the generalized relativistic Kramers equation in the phase space in external force fields is derived. The obtained diffusion equation is invariant under Lorentz transformations and its stationary solution is given by the Juttner distribution. Besides, a nonstationary analytical solution is derived for the example of force-free relativistic diffusion. PMID- 20364951 TI - Ab initio method for locating characteristic potential-energy minima of liquids. AB - It is possible in principle to probe the many-atom potential surface using density functional theory (DFT). This will allow us to apply DFT to the Hamiltonian formulation of atomic motion in monatomic liquids by Wallace [Phys. Rev. E 56, 4179 (1997)]. For a monatomic system, analysis of the potential surface is facilitated by the random and symmetric classification of potential energy valleys. Since the random valleys are numerically dominant and uniform in their macroscopic potential properties, only a few quenches are necessary to establish these properties. Here we describe an efficient technique for doing this. Quenches are done from easily generated "stochastic" configurations, in which the nuclei are distributed uniformly within a constraint limiting the closeness of approach. For metallic Na with atomic pair potential interactions, it is shown that quenches from stochastic configurations and quenches from equilibrium liquid molecular dynamics configurations produce statistically identical distributions of the structural potential energy. Again for metallic Na, it is shown that DFT quenches from stochastic configurations provide the parameters which calibrate the Hamiltonian. A statistical mechanical analysis shows how the underlying potential properties can be extracted from the distributions found in quenches from stochastic configurations. PMID- 20364952 TI - Hard versus soft dynamics for adsorption-desorption kinetics: Exact results in one-dimension. AB - The adsorption-desorption kinetics is discussed in the framework of the kinetic lattice-gas model. The master equation formalism has been introduced to describe the evolution of the system, where the transition probabilities are written as an expansion of the occupation configurations of all neighboring sites. Since the detailed balance principle determines half of the coefficients that arise from the expansion, it is necessary to introduce ad hoc, a dynamic scheme to get the rest of them. Three schemes of the so-called hard dynamics, in which the probability of transition from single site cannot be factored into a part which depends only on the interaction energy and one that only depends on the field energy, and five schemes of the so-called soft dynamics, in which this factorization is possible, were introduced for this purpose. It is observed that for the hard dynamic schemes, the equilibrium and nonequilibrium observables, such as adsorption isotherms, sticking coefficients, and thermal desorption spectra, have a normal or physical sustainable behavior. While for the soft dynamics schemes, with the exception of the transition state theory, the equilibrium and nonequilibrium observables have several problems. Some of them can be regarded as abnormal behavior. PMID- 20364953 TI - Multiplicative Levy processes: Ito versus Stratonovich interpretation. AB - Langevin equation with a multiplicative stochastic force is considered. That force is uncorrelated, it has the Levy distribution and the power-law intensity. The Fokker-Planck equations, which correspond both to the Ito and Stratonovich interpretation, are presented. They are solved for the case without drift and for the harmonic oscillator potential. The variance is evaluated; it is always infinite for the Ito case whereas for the Stratonovich one it can be finite and rise with time slower that linearly, which indicates subdiffusion. Analytical results are compared with numerical simulations. PMID- 20364954 TI - Coagulation reactions in low dimensions: Revisiting subdiffusive A+A reactions in one dimension. AB - We present a theory for the coagulation reaction A+A-->A for particles moving subdiffusively in one dimension. Our theory is tested against numerical simulations of the concentration of A particles as a function of time ("anomalous kinetics") and of the interparticle distribution function as a function of interparticle distance and time. We find that the theory captures the correct behavior asymptotically and also at early times, and that it does so whether the particles are nearly diffusive or very subdiffusive. We find that, as in the normal diffusion problem, an interparticle gap responsible for the anomalous kinetics develops and grows with time. This corrects an earlier claim to the contrary on our part. PMID- 20364955 TI - Velocity and cluster distributions in a bottleneck system. AB - Velocity and cluster distributions for particles with unidirectional motion in one dimension are studied. The particles never pass each other, like cars on a narrow road that does not allow overtaking. As a result, particles cluster behind slow particles (queues are formed behind slow cars). Thus, the actual velocity of each particle is to a large extent determined by slow particles further ahead. Considering all possible permutations of N particles with initial velocities {vi}, the average number of particles with actual velocity vi is (N+1)/[i(i+1)] (in the sequence {vi}, the initial velocities are listed with monotonically increasing values). For i large and vi proportional, variant i the average number of actual velocities is thus a power law in vi, even though the average cluster density is found to be independent of cluster size, L. On the other hand, the cluster density varies significantly with cluster velocity; we obtain [(N-i)!(N L)!]/[NN!(N-L-i+1)!]. The average velocity at a given position in the sequence of N particles, and the average global velocity are determined. Explicit results for several distributions of the initial velocities show that the global velocity depends sensitively on the form of this distribution. PMID- 20364956 TI - Experimental realization of directed percolation criticality in turbulent liquid crystals. AB - This is a comprehensive report on the phase transition between two turbulent states of electroconvection in nematic liquid crystals, which was recently found by the authors to be in the directed percolation (DP) universality class [K. A. Takeuchi, Phys. Rev. Lett. 99, 234503 (2007)]. We further investigate both static and dynamic critical behaviors of this phase transition, measuring a total of 12 critical exponents, 5 scaling functions, and 8 scaling relations, all in full agreement with those characterizing the DP class in 2+1 dimensions. Developing an experimental technique to create a seed of topological-defect turbulence by pulse laser, we confirm in particular the rapidity symmetry, which is a basic but nontrivial consequence of the field-theoretic approach to DP. This provides a clear experimental realization of this outstanding truly out-of-equilibrium universality class, dominating most phase transitions into an absorbing state. PMID- 20364957 TI - Phase diagram and critical behavior of the square-lattice Ising model with competing nearest-neighbor and next-nearest-neighbor interactions. AB - Using the parallel tempering algorithm and graphics processing unit accelerated techniques, we have performed large-scale Monte Carlo simulations of the Ising model on a square lattice with antiferromagnetic (repulsive) nearest-neighbor and next-nearest-neighbor interactions of the same strength and subject to a uniform magnetic field. Both transitions from the (2x1) and row-shifted (2x2) ordered phases to the paramagnetic phase are continuous. From our data analysis, re entrance behavior of the (2x1) critical line and a bicritical point which separates the two ordered phases at T=0 are confirmed. Based on the critical exponents we obtained along the phase boundary, Suzuki's weak universality seems to hold. PMID- 20364958 TI - Asymptotic shape of the region visited by an Eulerian walker. AB - We study an Eulerian walker on a square lattice, starting from an initial randomly oriented background using Monte Carlo simulations. We present evidence that, for a large number of steps N , the asymptotic shape of the set of sites visited by the walker is a perfect circle. The radius of the circle increases as N1/3, for large N , and the width of the boundary region grows as Nalpha/3, with alpha=0.40+/-0.06 . If we introduce stochasticity in the evolution rules, the mean-square displacement of the walker, approximately approximately N2nu, shows a crossover from the Eulerian (nu=1/3) to a simple random-walk (nu=1/2) behavior. PMID- 20364959 TI - Queueing process with excluded-volume effect. AB - We introduce an extension of the M/M/1 queueing process with a spatial structure and excluded-volume effect. The rule of particle hopping is the same as for the totally asymmetric simple exclusion process (TASEP). A stationary-state solution is constructed in a slightly arranged matrix product form of the open TASEP. We obtain the critical line that separates the parameter space depending on whether the model has the stationary state. We calculate the average length of the model and the number of particles and show the monotonicity of the probability of the length in the stationary state. We also consider a generalization of the model with backward hopping of particles allowed and an alternate joined system of the M/M/1 queueing process and the open TASEP. PMID- 20364960 TI - Trapping in scale-free networks with hierarchical organization of modularity. AB - A wide variety of real-life networks share two remarkable generic topological properties: scale-free behavior and modular organization, and it is natural and important to study how these two features affect the dynamical processes taking place on such networks. In this paper, we investigate a simple stochastic process -trapping problem, a random walk with a perfect trap fixed at a given location, performed on a family of hierarchical networks that exhibit simultaneously striking scale-free and modular structure. We focus on a particular case with the immobile trap positioned at the hub node having the largest degree. Using a method based on generating functions, we determine explicitly the mean first passage time (MFPT) for the trapping problem, which is the mean of the node-to trap first-passage time over the entire network. The exact expression for the MFPT is calculated through the recurrence relations derived from the special construction of the hierarchical networks. The obtained rigorous formula corroborated by extensive direct numerical calculations exhibits that the MFPT grows algebraically with the network order. Concretely, the MFPT increases as a power-law function of the number of nodes with the exponent much less than 1. We demonstrate that the hierarchical networks under consideration have more efficient structure for transport by diffusion in contrast with other analytically soluble media including some previously studied scale-free networks. We argue that the scale-free and modular topologies are responsible for the high efficiency of the trapping process on the hierarchical networks. PMID- 20364961 TI - Negative mobility induced by colored thermal fluctuations. AB - Anomalous transport of non-Markovian thermal Brownian particle dynamics in spatially periodic symmetric systems that is driven by time-periodic symmetric driving and constant bias is investigated numerically. The Brownian dynamics is modeled by a generalized Langevin equation with exponentially correlated Gaussian thermal noise, obeying the fluctuation-dissipation theorem. We study the role of nonzero correlation time of thermal fluctuations for the occurrence of absolute negative (linear) mobility (ANM) near zero bias, negative-valued, nonlinear mobility (NNM), and negative differential mobility (NDM) at finite bias away from equilibrium. We detect that a nonzero thermal correlation time can either enhance or also diminish the value of ANM. Moreover, finite thermal noise correlation can induce NDM and NNM in regions of parameter space for which such ANM and NNM behaviors are distinctly absent for limiting white thermal noise. In parts of the parameter space, we find a complex structure of regions of linear and nonlinear negative mobility: islands and tongues which emerge and vanish under parameters manipulation. While certain such anomalous transport regimes fade away with increasing temperature some specific regions interestingly remain rather robust. Outside those regimes with anomalous mobility, the ac/dc driven transport is either normal or the driven Brownian particles are not transported at all. PMID- 20364962 TI - Analytical expressions for the fourth virial coefficient of a hard-sphere mixture. AB - A method of numerical calculation of the fourth virial coefficients of the mixture of additive hard spheres is proposed. The results are compared with an exact analytical formula for the fourth partial virial coefficient B4[1] (i.e., three spheres of diameters sigma1 and one sphere of diameter sigma2) and a semiempirical expression for B4[2] (i.e., two spheres of each kind). It is shown that the first formula is nonanalytic and the implication to the equations of state for hard-sphere mixtures is discussed. PMID- 20364963 TI - Proposal and applications of a method for the study of irreversible phase transitions. AB - The gradient method for the study of irreversible phase transitions in far-from equilibrium lattice systems is proposed and successfully applied to both the archetypical case of the Ziff-Gulari-Barshad model [R. M. Ziff, Phys. Rev. Lett. 56, 2553 (1986)] and a forest-fire cellular automaton. By setting a gradient of the control parameter along one axis of the lattice, one can simultaneously treat both the active and the inactive phases of the system. In this way different interfaces are defined whose study allows us to find the active-inactive phase transition (both of first and second order), as well as the description of the active phase as composed of two further phases: the percolating and the nonpercolating ones. The average location and the width of the interfaces obey standard scaling behavior that is essentially governed by the roughness exponent alpha=1/(1+nu) , where nu is the suitable correlation length exponent. PMID- 20364964 TI - Dual structures of chaos and turbulence, and their dynamic scaling laws. AB - The decay form of the time correlation function Un(t) of a state variable un(t) with a small wave number kn has been shown to take the algebraic decay 1/{1+(gammanat)2} in the initial regime ttaun(gamma), where taun(gamma) denotes the decay time of the memory function Gamman(t). This dual structure of Un(t) is generated by the deterministic short orbits in the initial regime and the stochastic long orbits in the final regime, thus giving the outstanding features of chaos and turbulence. The kn dependence of gammana, alphane, and gammane is obtained for the chaotic Kuramoto-Sivashinsky equation, and it is shown that if kn is sufficiently small, then the dual structure of Un(t) obeys a hydrodynamic scaling law in the final regime t>tau(gamma) with scaling exponent z=2 and a dynamic scaling law in the initial regime t, both in two and three dimensions. Contrary to expectation, C(r) does not show any oscillatory behavior, rather decays exponentially and the effective persistence length has strong length dependence for short polymers. We also compute the distribution function P(R) of the end to end distance R and show how curved chains can be distinguished from wormlike chains using loop formation probability. PMID- 20365004 TI - Theory of a reconstructive structural transformation in capsids of icosahedral viruses. AB - A theory of a reconstructive structural transformation in icosahedral capsid shells is developed for a whole family of virulent human viruses. It is shown that the reversible rearrangement of proteins during the virus maturation transformation is driven by the variation in the wave number l associated with the protein density distribution function. The collective displacement field of protein centers from their positions in the initial (procapsid) and the final (capsid) two-dimensional icosahderal structures is derived. The amplitude of the displacement field is shown to be small and it minimizes the calculated free energy of the transformation. The theory allows us to propose a continuous thermodynamical mechanism of the reconstructive procapsid-to-capsid transformation. In the frame of the density-wave approach, we also propose to take an equivalent plane-wave vector as a common structural feature for different icosahedral capsid shells formed by the same proteins. Using these characteristics, we explain the relation between the radii of the procapsid and capsid shells and generalize it to the case of the viral capsid polymorphism. PMID- 20365005 TI - Dynamical activities of primary somatosensory cortices studied by magnetoencephalography. AB - A blind identification method of transfer functions in feedback systems is introduced for examination of dynamical activities of cortices by magnetoencephalography study. Somatosensory activities are examined in 5 Hz periodical median nerve stimulus. In the present paper, we will try two careful preprocessing procedures for the identification method to obtain impulse responses between primary somatosensory cortices. Time series data of the somatosensory evoked field are obtained by using a blind source separation of the T/k type (fractional) decorrelation method. Time series data of current dipoles of primary somatosensory cortices are transformed from the time series data of the somatosensory evoked field by the inverse problem. Fluctuations of current dipoles of them are obtained after elimination of deterministic periodical evoked waveforms. An identification method based on feedback system theory is used for estimation of transfer functions in a feedback model from obtained fluctuations of currents dipoles of primary somatosensory cortices. Dynamical activities between them are presented by Bode diagrams of transfer functions and their impulse responses: the time delay of about 30 ms via corpus callosum is found in the impulse response of identified transfer function. PMID- 20365006 TI - Model for amorphous aggregation processes. AB - The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first applications of the model, we have tested it against experimental turbidimetry data of three proteins relevant to the wine industry and biochemistry, namely, thaumatin, a thaumatinlike protein, and alpha lactalbumin. The model is very robust and describes amorphous experimental data to a high degree of accuracy. Details about the aggregation process, such as shape parameters of the aggregates and rate constants, can also be extracted. PMID- 20365007 TI - Formation and growth of lipofuscin in the retinal pigment epithelium cells. AB - The kinetics of lipofuscin growth in diseased retinal pigment epithelium cells is investigated using Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. Model simulations are compared to the number of lipofuscin granules in eyes with early age-related degeneration. PMID- 20365008 TI - Detection of protein secondary structures via the discrete wavelet transform. AB - We subject the primary sequence of proteins gathered from the Structural Classification of Proteins (SCOP) database to a discrete wavelet transform (DWT) analysis to search for predictors of secondary structures. We use proteins with both alpha helices and beta sheets (the A/B , A+B databases from SCOP). The amino acids composing the protein are converted to their hydrophobicity values using three hydrophobicity scales. Results prove to be independent of the scale used. Using a DWT multiresolution decomposition, each protein is coarse grained, in effect, creating snapshots of each protein at multiple scales. For each protein, a control data set is formed by generating random realizations that remove the positional informational in the sequence but still contain the same amino acid frequencies. Regions of salient hydrophobicity in the protein sequence are identified by comparing the transforms of the original sequence with those of the control set, at each resolution. We find significant matching between regions of salient hydrophobicity and the locations of secondary structure along the amino acid chains. We calculate the sensitivity, specificity, and Matthews correlation to quantify the agreement between the wavelet detected structures and the real protein. In addition we are able to distinguish between the morphologically different subsets, A/B and A+B. We also construct a correlation function based on the DWT that correlates quasilocalized structures at lengths in wavelet space. Through a similar comparison to the control data sets, features in this space scale correlation are identified that show correspondence to the typical lengths of the secondary structures. PMID- 20365009 TI - Growing heterogeneous tumors in silico. AB - An in silico tool that can be utilized in the clinic to predict neoplastic progression and propose individualized treatment strategies is the holy grail of computational tumor modeling. Building such a tool requires the development and successful integration of a number of biophysical and mathematical models. In this paper, we work toward this long-term goal by formulating a cellular automaton model of tumor growth that accounts for several different inter-tumor processes and host-tumor interactions. In particular, the algorithm couples the remodeling of the microvasculature with the evolution of the tumor mass and considers the impact that organ-imposed physical confinement and environmental heterogeneity have on tumor size and shape. Furthermore, the algorithm is able to account for cell-level heterogeneity, allowing us to explore the likelihood that different advantageous and deleterious mutations survive in the tumor cell population. This computational tool we have built has a number of applications in its current form in both predicting tumor growth and predicting response to treatment. Moreover, the latent power of our algorithm is that it also suggests other tumor-related processes that need to be accounted for and calls for the conduction of new experiments to validate the model's predictions. PMID- 20365010 TI - Enhanced low-Reynolds-number propulsion in heterogeneous viscous environments. AB - It has been known for some time that some microorganisms can swim faster in high viscosity gel-forming polymer solutions. These gel-like media come to mimic highly viscous heterogeneous environment that these microorganisms encounter in vivo. The qualitative explanation of this phenomena first offered by Berg and Turner [Nature (London) 278, 349 (1979)], suggests that propulsion enhancement is a result of flagellum pushing on quasi-rigid loose polymer network formed in some polymer solutions. Inspired by these observations, inertia-less propulsion in a heterogeneous viscous medium composed of sparse array of stationary obstacles embedded into a incompressible Newtonian liquid is considered. It is demonstrated that for prescribed propulsion gaits, including propagating surface distortions and rotating helical filament, the propulsion speed is enhanced when compared to swimming in purely viscous solvent. It is also shown that the locomotion in heterogenous viscous media is characterized by improved hydrodynamic efficiency. The results of the rigorous numerical simulation of the rotating helical filament propelled through a random sparse array of stationary obstructions are in close agreement with predictions of the proposed resistive force theory based on effective media approximation. PMID- 20365011 TI - Statistical physics of cerebral embolization leading to stroke. AB - We discuss the physics of embolic stroke using a minimal model of emboli moving through the cerebral arteries. Our model of the blood flow network consists of a bifurcating tree into which we introduce particles (emboli) that halt flow on reaching a node of similar size. Flow is weighted away from blocked arteries inducing an effective interaction between emboli. We justify the form of the flow weighting using a steady flow (Poiseuille) analysis and a more complicated nonlinear analysis. We discuss free flowing and heavily congested limits and examine the transition from free flow to congestion using numerics. The correlation time is found to increase significantly at a critical value and a finite-size scaling is carried out. An order parameter for nonequilibrium critical behavior is identified as the overlap of blockages' flow shadows. Our work shows embolic stroke to be a feature of the cerebral blood flow network on the verge of a phase transition. PMID- 20365012 TI - Arterial wall tethering as a distant boundary condition. AB - A standing difficulty in the problem of blood vessel tethering has been that only one of the two required boundary conditions can be fully specified, namely, that at the inner (endothelial) wall surface. The other, at the outer layer of the vessel wall, is not known except in the limiting case where the wall is fully tethered such that its outer layer is prevented from any displacement. In all other cases, where the wall is either free or partially tethered, a direct boundary condition is not available. We present a method of determining this missing boundary condition by considering the limiting case of a semi-infinite wall. The result makes it possible to define the degree of tethering imposed by surrounding tissue more accurately in terms of the displacement of the outer layer of the vessel wall, rather than in terms of equivalent added mass which has been done in the past. This new approach makes it possible for the first time to describe the effect of partial tethering in its full range, from zero to full tethering. The results indicate that high tethering leads to high stresses and low displacements within the vessel wall, while low tethering leads to low stresses and high displacements. Since both extremes would be damaging to wall tissue, particularly elastin, this suggest that moderate tethering would be optimum in the physiological setting. PMID- 20365013 TI - Response of a Hodgkin-Huxley neuron to a high-frequency input. AB - We study the response of a Hodgkin-Huxley neuron stimulated by a periodic sequence of conductance pulses arriving through the synapse in the high-frequency regime. In addition to the usual excitation threshold there is a smooth crossover from the firing to the silent regime for increasing pulse amplitude gsyn. The amplitude of the voltage spikes decreases approximately linearly with gsyn. In some regions of parameter space the response is irregular, probably chaotic. In the chaotic regime between the mode-locked regions 3:1 and 2:1 near the lower excitation threshold, the output interspike interval histogram (ISIH) undergoes a sharp transition. If the driving period is below the critical value, TT* even multiples of Ti also appear in the histogram, starting from the largest values. Near T* the ISIH scales logarithmically on both sides of the transition. The coefficient of variation of ISIH has a cusp singularity at T*. The average response period has a maximum slightly above T*. Near the excitation threshold in the chaotic regime the average firing rate rises sublinearly from frequencies of order 1 Hz. PMID- 20365014 TI - Cluster approximations for infection dynamics on random networks. AB - In this paper, we consider a simple stochastic epidemic model on large regular random graphs and the stochastic process that corresponds to this dynamics in the standard pair approximation. Using the fact that the nodes of a pair are unlikely to share neighbors, we derive the master equation for this process and obtain from the system size expansion the power spectrum of the fluctuations in the quasistationary state. We show that whenever the pair approximation deterministic equations give an accurate description of the behavior of the system in the thermodynamic limit, the power spectrum of the fluctuations measured in long simulations is well approximated by the analytical power spectrum. If this assumption breaks down, then the cluster approximation must be carried out beyond the level of pairs. We construct an uncorrelated triplet approximation that captures the behavior of the system in a region of parameter space where the pair approximation fails to give a good quantitative or even qualitative agreement. For these parameter values, the power spectrum of the fluctuations in finite systems can be computed analytically from the master equation of the corresponding stochastic process. PMID- 20365015 TI - Scaling and self-organized criticality in proteins: Lysozyme c. AB - Proteins appear to be the most dramatic natural example of self-organized criticality (SOC), a concept that explains many otherwise apparently unlikely phenomena. Protein functionality is often dominated by long-range hydro(phobic/philic) interactions, which both drive protein compaction and mediate protein-protein interactions. In contrast to previous reductionist short range hydrophobicity scales, the holistic Moret-Zebende hydrophobicity scale [Phys. Rev. E 75, 011920 (2007)] represents a hydroanalytic tool that bioinformatically quantifies SOC in a way fully compatible with evolution. Hydroprofiling identifies chemical trends in the activities and substrate binding abilities of model enzymes and antibiotic animal lysozymes c , as well as defensins, which have been the subject of tens of thousands of experimental studies. The analysis is simple and easily performed and immediately yields insights not obtainable by traditional methods based on short-range real-space interactions, as described either by classical force fields used in molecular dynamics simulations, or hydrophobicity scales based on transference energies from water to organic solvents or solvent-accessible areas. PMID- 20365016 TI - Phase statistics approach to human ventricular fibrillation. AB - Ventricular fibrillation (VF) is known to be the most dangerous cardiac arrhythmia, frequently leading to sudden cardiac death (SCD). During VF, cardiac output drops to nil and, unless the fibrillation is promptly halted, death usually ensues within minutes. While delivering life saving electrical shocks is a method of preventing SCD, it has been recognized that some, though not many, VF episodes are self-terminating, and understanding the mechanism of spontaneous defibrillation might provide newer therapeutic options for treatment of this otherwise fatal arrhythmia. Using the phase statistics approach, recently developed to study financial and physiological time series, here, we reveal the timing characteristics of transient features of ventricular tachyarrhythmia (mostly VF) electrocardiogram (ECG) and find that there are three distinct types of probability density function (PDF) of phase distributions: uniform (UF), concave (CC), and convex (CV). Our data show that VF patients with UF or CC types of PDF have approximately the same probability of survival and nonsurvival, while VF patients with CV type PDF have zero probability of survival, implying that their VF episodes are never self-terminating. Our results suggest that detailed phase statistics of human ECG data may be a key to understanding the mechanism of spontaneous defibrillation of fatal VF. PMID- 20365017 TI - Fronts from two-dimensional dispersal kernels: Beyond the nonoverlapping generations model. AB - Most integrodifference models of biological invasions are based on the nonoverlapping-generations approximation. However, the effect of multiple reproduction events (overlapping generations) on the front speed can be very important (especially for species with a long life spam). Only in one-dimensional space has this approximation been relaxed previously, although almost all biological invasions take place in two dimensions. Here we present a model that takes into account the overlapping generations effect (or, more generally, the stage structure of the population), and we analyze the main differences with the corresponding nonoverlapping-generations results. PMID- 20365018 TI - Statistical-mechanical study of evolution of robustness in noisy environments. AB - In biological systems, expression dynamics that can provide fitted phenotype patterns with respect to a specific function have evolved through mutations. This has been observed in the evolution of proteins for realizing folding dynamics through which a target structure is shaped. We study this evolutionary process by introducing a statistical-mechanical model of interacting spins, where a configuration of spins and their interactions J represent a phenotype and genotype, respectively. The phenotype dynamics are given by a stochastic process with temperature TS under a Hamiltonian with J. The evolution of J is also stochastic with temperature TJ and follows mutations introduced into J and selection based on a fitness defined for a configuration of a given set of target spins. Below a certain temperature TS(c2), the interactions J that achieve the target pattern evolve, whereas another phase transition is observed at TS(c1)Tc. It was found that Ar wets all the investigated surfaces. The adsorption isotherms for alkali metals exhibit first-order phase transitions. Prewetting lines were resolved even for the less attractive surfaces. In the cases of Mg, CO2 , and Au a continuous growth for T> or =Tt was obtained. A comparison with experimental data and other microscopic calculations is reported. PMID- 20365028 TI - Onset of initial planar instability with surface-tension anisotropy during directional solidification. AB - A simple model is presented to describe the variation of the onset of the initial planar instability with surface tension anisotropy during directional solidification. The effect of surface-tension anisotropy on the incubation time and the initial average wavelength of planar instability are predicted by the simple model quantitatively, which are also verified by phase field simulation. Investigation results reveal that surface-tension anisotropy is one of important factors in the dynamic process of planar instability. The contribution of surface tension anisotropy to the tilting modulation is also analyzed by comparing the results from the present simple model with those from phase field simulation. PMID- 20365029 TI - Bending affects entropy of semiflexible polymers: Application to protein-DNA complexes. AB - We discuss a class of generalized wormlike chain models of polymers with spontaneous curvature and show that the density of states and consequently the entropy of such natively bent polymers are higher than that of straight ones. This effect changes the classical Langmuir binding isotherm by giving rise to enhanced binding of DNA-bending proteins. PMID- 20365030 TI - Measurement of the temperature profile of an exothermic autocatalytic reaction front. AB - Autocatalytic reactions may propagate as solitary waves, namely, at a constant front velocity and with a stationary concentration profile, resulting from a balance between molecular diffusion and chemical reaction. When the reaction is exothermic, a thermal wave is linked to the chemical front. As the thermal diffusivity is nearly two orders of magnitude larger than the molecular one, the temperature profile spreads over length scales (mm) two orders of magnitude larger than the concentration one. Using an infrared camera, we measure the temperature profiles for a chlorite-tetrathionate autocatalytic reaction. The profiles are compared quantitatively to lattice Bhatnagar-Gross-Krook (BGK) numerical simulations. Our analysis also accounts for the lack of observation of the thermal wave for the iodate arsenous acid reaction. PMID- 20365031 TI - Coarsening of precipitation patterns in a moving reaction-diffusion front. AB - Precipitation patterns emerging in a two-dimensional moving front are investigated on the example of NaOH diffusing into a gel containing AlCl3 . The time evolution of the precipitate Al(OH)_{3} can be observed since the precipitate redissolves in the excess outer electrolyte NaOH and thus it exists only in a narrow optically accessible region of the reaction front. The patterns display self-similar coarsening with a characteristic length xi increasing with time as xi(t) approximately sqrt[t] . A theory based on the Cahn-Hilliard phase separation dynamics, including redissolution, is shown to yield agreement with the experiments. PMID- 20365032 TI - Fractal Weyl law behavior in an open Hamiltonian system. AB - We numerically show fractal Weyl law behavior in an open Hamiltonian system that is described by a smooth potential and which supports numerous above-barrier resonances. This behavior holds even relatively far away from the classical limit. The complex resonance wave functions are found to be localized on the fractal classical repeller. PMID- 20365033 TI - Reconnecting flux-rope dynamo. AB - We develop a model of the fluctuation dynamo in which the magnetic field is confined to thin flux ropes advected by a multiscale model of turbulence. Magnetic dissipation occurs only via reconnection of the flux ropes. This model can be viewed as an implementation of the asymptotic limit R_{m}-->infinity for a continuous magnetic field, where magnetic dissipation is strongly localized to small regions of strong-field gradients. We investigate the kinetic-energy release into heat mediated by the dynamo action, both in our model and by solving the induction equation with the same flow. We find that a flux-rope dynamo is an order of magnitude more efficient at converting mechanical energy into heat. The probability density of the magnetic energy release in reconnections has a power law form with the slope -3 , consistent with the solar corona heating by nanoflares. PMID- 20365034 TI - Effects of surface tension and viscosity on the growth rates of Rayleigh-Taylor and Richtmyer-Meshkov instabilities. AB - We present an analytical model for unstable interfaces with surface tension in fluids of arbitrary viscosity. Linear and nonlinear asymptotic solutions are obtained for growth rates of Rayleigh-Taylor and Richtmyer-Meshkov instabilities. In Rayleigh-Taylor instability, both surface tension and viscosity decrease the asymptotic bubble velocity. For Richtmyer-Meshkov instability, the analysis of the model suggests a dependence of the decaying rate of the bubble velocity on the relative importance of viscosity and surface tension. Results of numerical simulations are also given, and comparisons of the solutions of the model with numerical results are in good agreement. PMID- 20365035 TI - Numerical simulation of harmonic generation by relativistic laser interaction with a grating. AB - The interaction of a femtosecond relativistic intensity laser pulse with a grating of subwavelength periodicity was simulated numerically. Strong coherent emission at the wavelength of the grating period and its harmonics was seen, nearly parallel to the target surface, due to relativistic electron bunches emanating from each protuberance. Normal and oblique incidence (30 degrees ) gave rise to trains of attosecond pulses and an efficiency greater than 10;{-4} was obtained for the 24;{th} harmonic (lambda approximately 16.7 nm) . Similarity theory gives optimum conditions for harmonic emission. PMID- 20365036 TI - Characterization of two distinct, simultaneous hot electron beams in intense laser-solid interactions. AB - The transport of energetic electron beams generated from aluminum foils irradiated by ultraintense laser pulses has been studied by imaging coherent transition radiation from the rear side of the target. Two distinct beams of MeV electrons are emitted from the target rear side at the same time. This measurement indicates that two different mechanisms, namely resonance absorption and jxB heating, accelerate the electrons at the targets front side and drive them to different directions, with different temperatures. This interpretation is consistent with 3D-particle-in-cell simulations. PMID- 20365037 TI - Phase transitions in traffic flow on multilane roads. AB - Based on empirical and numerical analyses of vehicular traffic, the physics of spatiotemporal phase transitions in traffic flow on multilane roads is revealed. The complex dynamics of moving jams observed in single vehicle data measured by video cameras on American highways is explained by the nucleation-interruption effect in synchronized flow, i.e., the spontaneous nucleation of a narrow moving jam with the subsequent jam dissolution. We find that (i) lane changing, vehicle merging from on-ramps, and vehicle leaving to off-ramps result in different traffic phases-free flow, synchronized flow, and wide moving jams-occurring and coexisting in different road lanes as well as in diverse phase transitions between the traffic phases; (ii) in synchronized flow, the phase transitions are responsible for a non-regular moving jam dynamics that explains measured single vehicle data: moving jams emerge and dissolve randomly at various road locations in different lanes; (iii) the phase transitions result also in diverse expanded general congested patterns occurring at closely located bottlenecks. PMID- 20365038 TI - Boolean networks with reliable dynamics. AB - We investigated the properties of Boolean networks that follow a given reliable trajectory in state space. A reliable trajectory is defined as a sequence of states, which is independent of the order in which the nodes are updated. We explored numerically the topology, the update functions, and the state space structure of these networks, which we constructed using a minimum number of links and the simplest update functions. We found that the clustering coefficient is larger than in random networks and that the probability distribution of three node motifs is similar to that found in gene regulation networks. Among the update functions, only a subset of all possible functions occurs, and they can be classified according to their probability. More homogeneous functions occur more often, leading to a dominance of canalyzing functions. Finally, we studied the entire state space of the networks. We observed that with increasing systems size, fixed points become more dominant, moving the networks close to the frozen phase. PMID- 20365039 TI - Diffusion of scientific credits and the ranking of scientists. AB - Recently, the abundance of digital data is enabling the implementation of graph based ranking algorithms that provide system level analysis for ranking publications and authors. Here, we take advantage of the entire Physical Review publication archive (1893-2006) to construct authors' networks where weighted edges, as measured from opportunely normalized citation counts, define a proxy for the mechanism of scientific credit transfer. On this network, we define a ranking method based on a diffusion algorithm that mimics the spreading of scientific credits on the network. We compare the results obtained with our algorithm with those obtained by local measures such as the citation count and provide a statistical analysis of the assignment of major career awards in the area of physics. A website where the algorithm is made available to perform customized rank analysis can be found at the address http://www.physauthorsrank.org. PMID- 20365040 TI - Phase diagrams for three-strategy evolutionary prisoner's dilemma games on regular graphs. AB - Evolutionary prisoner's dilemma games are studied with players located on square lattice and random regular graph defining four neighbors for each one. The players follow one of the three strategies: tit-for-tat, unconditional cooperation, and defection. The simplified payoff matrix is characterized by two parameters: the temptation b to choose defection and the cost c of inspection reducing the income of tit-for-tat. The strategy imitation from one of the neighbors is controlled by pairwise comparison at a fixed level of noise. Using Monte Carlo simulations and the extended versions of pair approximation we have evaluated the b-c phase diagrams indicating a rich plethora of phase transitions between stationary coexistence, absorbing, and oscillatory states, including continuous and discontinuous phase transitions. By reasonable costs the tit-for tat strategy prevents extinction of cooperators across the whole span of b determining the prisoner's dilemma game, irrespective of the connectivity structure. We also demonstrate that the system can exhibit a repetitive succession of oscillatory and stationary states upon changing a single payoff value, which highlights the remarkable sensitivity of cyclical interactions on the parameters that define the strength of dominance. PMID- 20365041 TI - Coevolution of Glauber-like Ising dynamics and topology. AB - We study the coevolution of a generalized Glauber dynamics for Ising spins with tunable threshold and of the graph topology where the dynamics takes place. This simple coevolution dynamics generates a rich phase diagram in the space of the two parameters of the model, the threshold and the rewiring probability. The diagram displays phase transitions of different types: spin ordering, percolation, and connectedness. At variance with traditional coevolution models, in which all spins of each connected component of the graph have equal value in the stationary state, we find that, for suitable choices of the parameters, the system may converge to a state in which spins of opposite sign coexist in the same component organized in compact clusters of like-signed spins. Mean field calculations enable one to estimate some features of the phase diagram. PMID- 20365042 TI - Revising the simple measures of assortativity in complex networks. AB - We find that traditional statistics for measuring degree mixing are strongly affected by superrich nodes. To counteract and measure the effect of superrich nodes, we propose a paradigm to quantify the mixing pattern of a real network in which different mixing patterns may appear among low-degree nodes and among high degree nodes. This paradigm and the simple revised measure uncover the true complex degree mixing patterns of complex networks with superrich nodes. The alternate method indicates that some networks show a false disassortative mixing induced by superrich nodes and have no tendency to be genuinely disassortative. Our results also show that the previously observed fragility of scale-free networks is actually greatly exacerbated by the presence of even a very small number of superrich nodes. PMID- 20365043 TI - Language structure in the n -object naming game. AB - We examine a naming game with two agents trying to establish a common vocabulary for n objects. Such efforts lead to the emergence of language that allows for an efficient communication and exhibits some degree of homonymy and synonymy. Although homonymy reduces the communication efficiency, it seems to be a dynamical trap that persists for a long, and perhaps indefinite, time. On the other hand, synonymy does not reduce the efficiency of communication but appears to be only a transient feature of the language. Thus, in our model the role of synonymy decreases and in the long-time limit it becomes negligible. A similar rareness of synonymy is observed in present natural languages. The role of noise, that distorts the communicated words, is also examined. Although, in general, the noise reduces the communication efficiency, it also regroups the words so that they are more evenly distributed within the available "verbal" space. PMID- 20365045 TI - Topology-independent impact of noise on cooperation in spatial public goods games. AB - We study the evolution of cooperation in public goods games on different regular graphs as a function of the noise level underlying strategy adoptions. We focus on the effects that are brought about by different group sizes of public goods games in which individuals participate, revealing that larger groups of players may induce qualitatively different behavior when approaching the deterministic limit of strategy adoption. While by pairwise interactions an intermediate uncertainty by strategy adoptions may ensure optimal conditions for the survival of cooperators at a specific graph topology, larger groups warrant this only in the vicinity of the deterministic limit independently from the underlying graph. These discrepancies are attributed to the indirect linkage of otherwise not directly connected players, which is brought about by joint memberships within the larger groups. Thus, we show that increasing the group size may introduce an effective transition of the interaction topology, and that the latter shapes the noise dependence of the evolution of cooperation in case of pairwise interactions only. PMID- 20365044 TI - Resonance, criticality, and emergence in city traffic investigated in cellular automaton models. AB - The complex behavior that occurs when traffic lights are synchronized is studied for a row of interacting cars. The system is modeled through a cellular automaton. Two strategies are considered: all lights in phase and a "green wave" with a propagating green signal. It is found that the mean velocity near the resonant condition follows a critical scaling law. For the green wave, it is shown that the mean velocity scaling law holds even for random separation between traffic lights and is not dependent on the density. This independence on car density is broken when random perturbations are considered in the car velocity. Random velocity perturbations also have the effect of leading the system to an emergent state, where cars move in clusters, but with an average velocity which is independent of traffic light switching for large injection rates. PMID- 20365046 TI - Random walker in temporally deforming higher-order potential forces observed in a financial crisis. AB - Basic peculiarities of market price fluctuations are known to be well described by a recently developed random-walk model in a temporally deforming quadratic potential force whose center is given by a moving average of past price traces [M. Takayasu, T. Mizuno, and H. Takayasu, Physica A 370, 91 (2006)]. By analyzing high-frequency financial time series of exceptional events, such as bubbles and crashes, we confirm the appearance of higher-order potential force in the markets. We show statistical significance of its existence by applying the information criterion. This time series analysis is expected to be applied widely for detecting a nonstationary symptom in random phenomena. PMID- 20365047 TI - Spontaneous traveling waves in oscillatory systems with cross diffusion. AB - We identify a type of pattern formation in spatially distributed active systems. We simulate one-dimensional two-component systems with predator-prey local interaction and pursuit-evasion taxis between the components. In a sufficiently large domain, spatially uniform oscillations in such systems are unstable with respect to small perturbations. This instability, through a transient regime appearing as spontaneous focal sources, leads to establishment of periodic traveling waves. The traveling wave regime is established even if boundary conditions do not favor such solutions. The stable wavelength is within a range bounded both from above and from below, and this range does not coincide with instability bands of the spatially uniform oscillations. PMID- 20365048 TI - Selection of noise level in strategy adoption for spatial social dilemmas. AB - We studied spatial Prisoner's Dilemma and Stag Hunt games where both the strategy distribution and the players' individual noise level could evolve to reach higher individual payoff. Players are located on the sites of different two-dimensional lattices and gain their payoff from games with their neighbors by choosing unconditional cooperation or defection. The way of strategy adoption can be characterized by a single K (temperaturelike) parameter describing how strongly adoptions depend on the payoff difference. If we start the system from a random strategy distribution with many different player specific K parameters, the simultaneous evolution of strategies and K parameters drives the system to a final stationary state where only one K value remains. In the coexistence phase of cooperator and defector strategies the surviving K parameter is in good agreement with the noise level that ensures the highest cooperation level if uniform K is supposed for all players. In this paper we give a thorough overview about the properties of this evolutionary process. PMID- 20365049 TI - Cavity approach to the Sourlas code system. AB - The statistical physics properties of regular and irregular Sourlas codes are investigated in this paper by the cavity method. At finite temperatures, the free energy density of these coding systems is derived and compared with the result obtained by the replica method. In the zero-temperature limit, the Shannon's bound is recovered in the case of infinite-body interactions while the code rate is still finite. However, the decoding performance as obtained by the replica theory has not considered the zero-temperature entropic effect. The cavity approach is able to consider the ground-state entropy. It leads to a set of evanescent cavity fields propagation equations which further improve the decoding performance as confirmed by our numerical simulations on single instances. For the irregular Sourlas code, we find that it takes the trade-off between good dynamical property and high performance of decoding. In agreement with the results found from the algorithmic point of view, the decoding exhibits a first order phase transition as occurs in the regular code system with three-body interactions. The cavity approach for the Sourlas code system can be extended to consider first-step replica symmetry breaking. PMID- 20365050 TI - Spectral properties of networks with community structure. AB - In this paper, we discuss the eigenspectra of networks with community structure. It is shown that in many cases, the spectrum of eigenvalues of the adjacency matrix of a network with community structure gives a clear indication of the number of communities in the network. In particular, for a network with N nodes and N_(c) communities, there will typically be N_(c) eigenvalues that are significantly larger than the magnitudes of all the other (N-N_(c)) eigenvalues. We discuss this property as well as its use and limitations for determining N_(c) . PMID- 20365051 TI - Quantum Zeno effect explains magnetic-sensitive radical-ion-pair reactions. AB - Chemical reactions involving radical-ion pairs are ubiquitous in biology, since not only are they at the basis of the photosynthetic reaction chain, but are also assumed to underlie the biochemical magnetic compass used by avian species for navigation. Recent experiments with magnetic-sensitive radical-ion-pair reactions provided strong evidence for the radical-ion-pair magnetoreception mechanism, verifying the expected magnetic sensitivities and chemical product yield changes. It is here shown that the theoretical description of radical-ion-pair reactions used since the 70s cannot explain the observed data, because it is based on phenomenological equations masking quantum coherence effects. The fundamental density-matrix equation derived here from basic quantum measurement theory considerations naturally incorporates the quantum Zeno effect and readily explains recent experimental observations on low- and high magnetic-field radical ion-pair reactions. PMID- 20365052 TI - Synchronization performance of complex oscillator networks. AB - Recently, synchronization of complex networks has attracted increasing attention from various research fields. However, most previous works focused on the stability of synchronization manifold. In this paper, we analyze the time-delay tolerance and converging speed of synchronization. Our theoretical analysis and extensive simulations show that the critical value of time delay for network synchronization is inversely proportional to the largest Laplacian eigenvalue, the converging speed without time delay is proportional to the second least Laplacian eigenvalue, and the time delay could increase the converging speed linearly for heterogeneous networks and significantly for homogeneous networks. PMID- 20365053 TI - Community detection algorithms: a comparative analysis. AB - Uncovering the community structure exhibited by real networks is a crucial step toward an understanding of complex systems that goes beyond the local organization of their constituents. Many algorithms have been proposed so far, but none of them has been subjected to strict tests to evaluate their performance. Most of the sporadic tests performed so far involved small networks with known community structure and/or artificial graphs with a simplified structure, which is very uncommon in real systems. Here we test several methods against a recently introduced class of benchmark graphs, with heterogeneous distributions of degree and community size. The methods are also tested against the benchmark by Girvan and Newman [Proc. Natl. Acad. Sci. U.S.A. 99, 7821 (2002)] and on random graphs. As a result of our analysis, three recent algorithms introduced by Rosvall and Bergstrom [Proc. Natl. Acad. Sci. U.S.A. 104, 7327 (2007); Proc. Natl. Acad. Sci. U.S.A. 105, 1118 (2008)], Blondel [J. Stat. Mech.: Theory Exp. (2008), P10008], and Ronhovde and Nussinov [Phys. Rev. E 80, 016109 (2009)] have an excellent performance, with the additional advantage of low computational complexity, which enables one to analyze large systems. PMID- 20365054 TI - Principal bifurcations and symmetries in the emergence of reaction-diffusion advection patterns on finite domains. AB - Pattern formation mechanisms of a reaction-diffusion-advection system, with one diffusivity, differential advection, and (Robin) boundary conditions of Danckwerts type, are being studied. Pattern selection requires mapping the domains of coexistence and stability of propagating or stationary nonuniform solutions, which for the general case of far from instability onsets, is conducted using spatial dynamics and numerical continuations. The selection is determined by the boundary conditions which either preserve or destroy the translational symmetry of the model. Accordingly, we explain the criterion and the properties of stationary periodic states if the system is bounded and show that propagation of nonlinear waves (including solitary) against the advective flow corresponds to coexisting family that emerges nonlinearly from a distinct oscillatory Hopf instability. Consequently, the resulting pattern selection is qualitatively different from the symmetric finite wavenumber Turing or Hopf instabilities. PMID- 20365055 TI - Asymptotic-boundary-layer method for unstable trajectories: semiclassical expansions for individual scar wave functions. AB - We extend the asymptotic boundary layer (ABL) method, originally developed for stable resonator modes, to the description of individual wave functions localized around unstable periodic orbits. The formalism applies to the description of scar states in fully or partially chaotic quantum systems, and also allows for the presence of smooth and sharp potentials, as well as magnetic fields. We argue that the separatrix wave function provides the largest contribution to the scars on a single wave function. This agrees with earlier results on the wave-function asymptotics and on the quantization condition of the scar states. Predictions of the ABL formalism are compared with the exact numerical solution for a strip resonator with a parabolic confinement potential and a magnetic field. PMID- 20365056 TI - Deformation of a self-propelled domain in an excitable reaction-diffusion system. AB - We formulate a theory for a self-propelled domain in an excitable reaction diffusion system in two dimensions where the domain deforms from a circular shape when the propagation velocity is increased. In the singular limit where the width of the domain boundary is infinitesimally thin, we derive a set of equations of motion for the center of gravity and two fundamental deformation modes. The deformed shapes of a steadily propagating domain are obtained. The set of time evolution equations exhibits a bifurcation from a straight motion to a circular motion by changing the system parameters. PMID- 20365057 TI - Nanopattern formation in self-assembled monolayers of thiol-capped Au nanocrystals. AB - The structure and the stability of the transferred monolayers of gold-thiol nanoparticles, formed at air-water interface at different surface pressure, on to silicon surface have been studied using two complementary techniques, x-ray reflectivity and atomic force microscopy (AFM). Networklike nanopatterns, observed through AFM, of the in-plane aggregated nanoparticles can be attributed to the late stage drying of the liquid trapped in the islands formed by nanoparticles. During drying process the trapped liquid leaves pinholes in the islands which by the process of nucleation and growth carry the mobile nanoparticles on their advancing fronts such that the nanoparticles are trapped at the boundaries of similar adjacent holes. This process continues bringing about in-plane as well as out-of-plane restructuring in the monolayer until the liquid evaporates completely rendering a patterned structure to the islands and instability in the monolayer is then stabilized. PMID- 20365058 TI - Adaptive synchronization of coupled chaotic oscillators. AB - We experimentally demonstrate and numerically simulate an adaptive method to maintain synchronization between coupled nonlinear chaotic oscillators, when the coupling between the systems is unknown and time-varying (e.g., due to environmental parameter drift). The technique is applied to optoelectronic feedback loops exhibiting high-dimensional chaotic dynamics. In addition to keeping the two systems isochronally synchronized in the presence of a priori unknown time-varying coupling strength, the technique provides an estimate of the time-varying coupling. PMID- 20365059 TI - Adaptive coupling for achieving stable synchronization of chaos. AB - We consider synchronization of coupled chaotic systems and propose an adaptive strategy that aims at evolving the strength of the coupling to achieve stability of the synchronized evolution. We test this idea in a simple configuration in which two chaotic systems (a sender and a receiver) are unidirectionally coupled and we study the conditions for the receiver to adaptively synchronize with the sender. Numerical simulations show that, under certain conditions, our strategy is successful in dynamically evolving the coupling strength until it converges to a value that is compatible with synchronization. PMID- 20365060 TI - Representation theory for strange attractors. AB - Embeddings are diffeomorphisms between some unseen physical attractor and a reconstructed image. Different embeddings may or may not be equivalent under isotopy. We regard embeddings as representations of the attractor, review the labels required to distinguish inequivalent representations for an important class of dynamical systems, and discuss the systematic ways inequivalent embeddings become equivalent as the embedding dimension increases until there is finally only one "universal" embedding in a suitable dimension. PMID- 20365061 TI - Spatial confinement controls self-oscillations in polymer gels undergoing the Belousov-Zhabotinsky reaction. AB - Chemoresponsive gels undergoing the Belousov-Zhabotinsky (BZ) reaction exhibit self-sustained pulsations, which can be harnessed to perform mechanical work. In technological applications, the gels would typically be confined between hard surfaces and thus, it is essential to establish how confinement affects these distinctive oscillations. Using theory and simulation, we pinpoint regions in phase space where the dynamic behavior of BZ gels critically depends on the presence of confining walls. We then illustrate how the wave propagation within thin samples can be tailored by selectively introducing "cut outs" in the bounding surfaces. The oscillations in the latter films are localized in specified areas, so the system contains well-defined oscillatory and nonoscillatory regions. The cut outs provide an effective means of tuning the mechanical action within the film and provide a route for tailoring the functionality of the material. PMID- 20365062 TI - Semiclassical transport in nearly symmetric quantum dots. I. Symmetry breaking in the dot. AB - We apply the semiclassical theory of transport to quantum dots with exact and approximate spatial symmetries; left-right mirror symmetry, up-down mirror symmetry, inversion symmetry, or fourfold symmetry. In this work-the first of a pair of articles-we consider (a) perfectly symmetric dots and (b) nearly symmetric dots in which the symmetry is broken by the dot's internal dynamics. The second article addresses symmetry-breaking by displacement of the leads. Using semiclassics, we identify the origin of the symmetry-induced interference effects that contribute to weak localization corrections and universal conductance fluctuations. For perfect spatial symmetry, we recover results previously found using the random-matrix theory conjecture. We then go on to show how the results are affected by asymmetries in the dot, magnetic fields, and decoherence. In particular, the symmetry-asymmetry crossover is found to be described by a universal dependence on an asymmetry parameter gamma_{asym} . However, the form of this parameter is very different depending on how the dot is deformed away from spatial symmetry. Symmetry-induced interference effects are completely destroyed when the dot's boundary is globally deformed by less than an electron wavelength. In contrast, these effects are only reduced by a finite amount when a part of the dot's boundary smaller than a lead-width is deformed an arbitrarily large distance. PMID- 20365063 TI - Semiclassical transport in nearly symmetric quantum dots. II. Symmetry breaking due to asymmetric leads. AB - In this work-the second of a pair of articles-we consider transport through spatially symmetric quantum dots with leads whose widths or positions do not obey the spatial symmetry. We use the semiclassical theory of transport to find the symmetry-induced contributions to weak localization corrections and universal conductance fluctuations for dots with left-right, up-down, inversion, and fourfold symmetries. We show that all these contributions are suppressed by asymmetric leads; however, they remain finite whenever leads intersect with their images under the symmetry operation. For an up-down symmetric dot, this means that the contributions can be finite even if one of the leads is completely asymmetric. We find that the suppression of the contributions to universal conductance fluctuations is the square of the suppression of contributions to weak localization. Finally, we develop a random-matrix theory model which enables us to numerically confirm these results. PMID- 20365064 TI - Transient spatiotemporal chaos is extensive in three reaction-diffusion networks. AB - Extensive (asymptotic) spatiotemporal chaos is comprised of statistically similar subsystems that interact only weakly. A systematic study of transient spatiotemporal chaos reveals extensive system behavior in all three reaction diffusion networks for various boundary conditions. The Lyapunov dimension, the sum of positive Lyapunov exponents, and the logarithm of the transient lifetime grow linearly with the system size. The unstable manifold of the chaotic saddle has nearly the same dimension as the saddle itself, and the stable manifold is nearly space filling. PMID- 20365065 TI - Dynamical thermalization of disordered nonlinear lattices. AB - We study numerically how the energy spreads over a finite disordered nonlinear one-dimensional lattice, where all linear modes are exponentially localized by disorder. We establish emergence of dynamical thermalization characterized as an ergodic chaotic dynamical state with a Gibbs distribution over the modes. Our results show that the fraction of thermalizing modes is finite and grows with the nonlinearity strength. PMID- 20365066 TI - Wave-vortex interaction. AB - We present an experimental study of the effect of an electromagnetically generated vortex flow on parametrically amplified waves at the surface of a vertically vibrated fluid layer. The underlying vortex flow, generated by a periodic Lorentz force, creates spatiotemporal fluctuations that nonlinearly interact with the standing surface waves. We measure the power spectral density of the surface wave amplitude and we characterize the bifurcation diagram by recording the subharmonic response of the surface to the external vibration. We show that the parametric instability is delayed in the presence of spatiotemporal fluctuations due to the vortex flow. In addition, the dependence of the amplitude of the subharmonic response on the distance to the instability threshold is modified. This shows that the nonlinear saturation mechanism of the waves is modified by the vortex flow. PMID- 20365067 TI - Mass transport subject to time-dependent flow with nonuniform sorption in porous media. AB - We address the description of solutes flow with trapping processes in porous media. Starting from a small-scale model for tracer particle trajectories, we derive the corresponding governing equations for the concentration of the mobile and immobile phases within a fractal mobile-immobile model approach. We show that this formulation is fairly general and can easily take into account nonconstant coefficients and in particular space-dependent sorption rates. The transport equations are solved numerically and a comparison with Monte Carlo particle tracking simulations of spatial contaminant profiles and breakthrough curves is proposed, so as to illustrate the obtained results. PMID- 20365068 TI - Large deviation theory for coin tossing and turbulence. AB - Large deviations play a significant role in many branches of nonequilibrium statistical physics. They are difficult to handle because their effects, though small, are not amenable to perturbation theory. Even the Gaussian model, which is the usual initial step for most perturbation theories, fails to be a starting point while discussing intermittency in fluid turbulence, where large deviations dominate. Our contention is: in the large deviation theory, the central role is played by the distribution associated with the tossing of a coin and the simple coin toss is the "Gaussian model" of problems where rare events play significant role. We illustrate this by applying it to calculate the multifractal exponents of the order structure factors in fully developed turbulence. PMID- 20365069 TI - Inconsistency of a dissipative contribution to the mass flux in hydrodynamics. AB - The possibility of dissipative contributions to the mass flux is considered in detail. A general thermodynamically consistent framework is developed to obtain such terms, the compatibility of which with general principles is then checked including Galilean invariance, the possibility of steady rigid rotation and uniform center-of-mass motion, the existence of a locally conserved angular momentum, and material objectivity. All previously discussed scenarios of dissipative mass fluxes are found to be ruled out by some combinations of these principles but not a new one that includes a smoothed velocity field v[over ] . However, this field v[over ] is nonlocal and leads to unacceptable consequences in specific situations. Hence, we can state with confidence that a dissipative contribution to the mass flux is not possible. PMID- 20365070 TI - Wave-driven dynamo action in spherical magnetohydrodynamic systems. AB - Hydrodynamic and magnetohydrodynamic numerical studies of a mechanically forced two-vortex flow inside a sphere are reported. The simulations are performed in the intermediate regime between the laminar flow and developed turbulence, where a hydrodynamic instability is found to generate internal waves with a characteristic m=2 zonal wave number. It is shown that this time-periodic flow acts as a dynamo, although snapshots of the flow as well as the mean flow are not dynamos. The magnetic fields' growth rate exhibits resonance effects depending on the wave frequency. Furthermore, a cyclic self-killing and self-recovering dynamo based on the relative alignment of the velocity and magnetic fields is presented. The phenomena are explained in terms of a mixing of nonorthogonal eigenstates of the time-dependent linear operator of the magnetic induction equation. The potential relevance of this mechanism to dynamo experiments is discussed. PMID- 20365071 TI - Pattern formation and interface pinch-off in rotating Hele-Shaw flows: a phase field approach. AB - Viscous fingering dynamics driven by centrifugal forcing is studied for arbitrary viscosity contrast. Theoretical methods, including exact solutions, and numerics based on a phase-field approach are used. Both confirm that pinch-off singularities in patterns originated from the centrifugally driven instability may occur spontaneously and be inherent to the two-dimensional Hele-Shaw dynamics. They are systematically more frequent for lower viscosity contrasts consistently with experimental evidence. The analytical insights provide an interpretation of this fact in terms of the asymptotic matching of the different regions of the fingering patterns. The phase-field numerical scheme is shown to be particularly adequate to elucidate the existence of finite-time singularities through the dependence of the singularity time on the interface thickness, in particular for varying viscosity contrast. PMID- 20365072 TI - Pinch-off singularities in rotating Hele-Shaw flows at high viscosity contrast. AB - We study the evolution of a family of dumbbell-shaped liquid patches surrounded by air inside a rotating Hele-Shaw cell with lubrication methods and numerical simulations. Depending on initial conditions, the dumbbell either stretches to infinity, pinches off at the neck to form a droplet, or collects into a circular drop at the center of rotation. Whether or not pinch-off occurs results from a subtle interplay between centrifugal and capillary forces. In particular, rotation may delay or even prevent pinch-off from occurring owing to stretching and smoothing of the fluid neck. However, frequently rotation may have the opposite effect leading to pinch-off where the relaxation toward a circular drop would be observed in an ordinary Hele-Shaw cell. PMID- 20365073 TI - Lagrangian transport induced by peristaltic pumping in a closed channel. AB - Lagrangian transport induced by peristaltic waves traveling on the boundaries of a two-dimensional rectangular closed channel is studied analytically. Based on the Lagrangian description, an asymptotic analysis is performed to generate explicit expressions for the leading-order oscillatory as well as the higher order time-mean mass transport (or steady streaming) velocities as functions of the wave properties. Two cases are considered. The first case, which is for slow wave frequency or very small wave amplitude such that the steady-streaming Reynolds number (Re_(s)) is very small, recovers the one studied previously in the literature, but with all the results fully presented in the Lagrangian sense. The second case, corresponding to high-frequency pumping such as Re_(s) is order unity, is where it has been handled analytically. It is found that the overall mixing resulting from the mass transport can depend on the phase shift of the two waves, the wave number, the frequency, as well as the amplitude of the waves. PMID- 20365074 TI - Absence of Marangoni convection at Marangoni numbers above 27,000 during water evaporation. AB - Two mechanisms by which Marangoni convection can be produced at the interface of water with its vapor are: (1) by imposing a temperature gradient parallel to the water-vapor interface, and (2) by imposing a temperature gradient perpendicular to the interface that results in the liquid becoming unstable. A series of evaporation experiments conducted with H2O and with D2O maintained at the mouth of a stainless-steel funnel indicated the presence of Marangoni convection, but the mechanism producing the convection was unclear. We have investigated the mechanism using a funnel constructed with a polymethyl methacrylate that has a small thermal conductivity relative to that of water and repeating the evaporation experiments. Marangoni convection was eliminated with this funnel even though the Marangoni number, Ma, was in the range 8277< or =Ma< or =27 847 . A comparison of the assumptions made in the theories available to predict the onset of Marangoni convection with the observations made in this study indicates some of the assumptions are invalid: although generally neglected, energy transport through the vapor to the interface of evaporating water is significant; there is an interfacial temperature discontinuity, but it is in the opposite direction of that assumed in the existing theories: the interfacial-vapor temperature is greater than that of the liquid during evaporation; and the prediction of the critical Marangoni number is based on an arbitrarily chosen value of the heat-transfer coefficient. When the temperature gradient is perpendicular to the water-vapor interface, these invalid assumptions indicate present theories do not apply to volatile liquids. PMID- 20365075 TI - Capillary filling in microchannels patterned by posts. AB - We investigate the capillary filling of three-dimensional microchannels with surfaces patterned by posts of square cross section. We show that pinning on the edges of the posts suppresses and can halt capillary filling. We stress the importance of the channel walls in controlling whether filling can occur. In particular for channels higher than the distance between adjacent posts, filling occurs for contact angles less than a threshold angle of approximately 55 degrees , independent of the height of the channel. PMID- 20365076 TI - Dynamic labyrinthine pattern in an active liquid film. AB - We report the generation of a dynamic labyrinthine pattern in an active alcohol film. A dynamic labyrinthine pattern is formed along the contact line of air/pentanol/aqueous three phases. The contact line shows a clear time-dependent change with regard to both perimeter and area of a domain. An autocorrelation analysis of time development of the dynamics of the perimeter and area revealed a strong geometric correlation between neighboring patterns. The pattern showed autoregressive behavior. The behavior of the dynamic pattern is strikingly different from those of stationary labyrinthine patterns. The essential aspects of the observed dynamic pattern are reproduced by a diffusion-controlled geometric model. PMID- 20365077 TI - Lower hybrid drift instability in a neutral sheet with O+ ions. AB - The electromagnetic lower-hybrid drift instability (LHDI) in the intermediate wavelength regime k_(y)sqrt[rho_(i)rho_(e)] approximately 1 , where k_(y) and rho_(e,i) are the wave vector and the electron and ion gyroradii, respectively, in a thin plasma sheet containing electrons and H+ and O+ ions is examined using kinetic theory. It is shown that the growth rate of the LHDI first decreases and then increases with increase in the O+ content and temperature, with a minimum at a moderate level of the latter. The results can be relevant to understanding magnetic reconnection in the presence of LHDI. PMID- 20365078 TI - Modeling of population kinetics of plasmas that are not in local thermodynamic equilibrium, using a versatile collisional-radiative model based on analytical rates. AB - We discuss the modeling of population kinetics of nonequilibrium steady-state plasmas using a collisional-radiative model and code based on analytical rates (ABAKO). ABAKO can be applied to low-to-high Z ions for a wide range of laboratory plasma conditions: coronal, local thermodynamic equilibrium or nonlocal thermodynamic equilibrium, and optically thin or thick plasmas. ABAKO combines a set of analytical approximations to atomic rates, which yield substantial savings in computer running time, still comparing well with more elaborate codes and experimental data. A simple approximation to calculate the electron capture cross section in terms of the collisional excitation cross section has been adapted to work in a detailed-configuration-accounting approach, thus allowing autoionizing states to be explicitly included in the kinetics in a fast and efficient way. Radiation transport effects in the atomic kinetics due to line trapping in the plasma are taken into account via geometry-dependent escape factors. Since the kinetics problem often involves very large sparse matrices, an iterative method is used to perform the matrix inversion. In order to illustrate the capabilities of the model, we present a number of results which show that the ABAKO compares well with customized models and simulations of ion population distribution. The utility of ABAKO for plasma spectroscopic applications is also outlined. PMID- 20365079 TI - Analytical expressions of the front shape of non-quasi-neutral plasma expansions with anisotropic electron pressures. AB - An analytical expression is proposed to describe the front shape of a non-quasi neutral plasma expansion with anisotropic electron pressures. It is of significance in the study of ultrashort plasma expansions generated from laser foil interactions and anisotropic astroplasma expansions in space science. It is found that the plasma front shape depends on the relationship between the ratio of the longitudinal and the transverse temperature of hot electrons kappa;(2) and the electron-ion mass ratio mu . For kappa;(2)(micro,1] , the ion front is a part of an ellipse and the major axis is in the lower-temperature axis. For kappa;(2)< or =micro , the ion front is composed by a part of a hyperbolic and a small pointed projection at the center. In the strongly anisotropic region, there is an ultrashort anomalous plasma emission of tens of femtoseconds at the angle of near 90 degrees . The ion-velocity distribution and angular-energy distribution at the ion front have also been given. Particularly, anomalous positron emissions exist in the electron-positron plasma anisotropic expansion. PMID- 20365080 TI - Brownian dynamic of laser cooling and crystallization of electron-ion plasma. AB - Laser cooling and crystallization of electron-ion plasma is studied using the Brownian dynamics simulation technique and taking into consideration the interaction of ions with the electron subsystem. It has been shown that the nonlinear dependence of laser friction force on the velocity of ions has to be taken into account in order to simulate in an adequate manner the cooling dynamics and obtain a correct estimate for minimum temperatures. It has been found that times required for formation of an ordered ionic structure can be much longer than the typical plasma cooling time. PMID- 20365081 TI - Arrest of Langmuir wave collapse by quantum effects. AB - The arrest of Langmuir wave collapse by quantum effects, first addressed by Haas and Shukla [Phys. Rev. E 79, 066402 (2009)] using a Rayleigh-Ritz trial function method is revisited, using rigorous estimates and systematic asymptotic expansions. The absence of blow up for the so-called quantum Zakharov equations is proved in two and three dimensions, whatever the strength of the quantum effects. The time-periodic behavior of the solution for initial conditions slightly in excess of the singularity threshold for the classical problem is established for various settings in two space dimensions. The difficulty of developing a consistent perturbative approach in three dimensions is also discussed and a semiphenomenological model is suggested for this case. PMID- 20365082 TI - Inverse bremsstrahlung absorption with nonlinear effects of high laser intensity and non-Maxwellian distribution. AB - Inverse bremsstrahlung (IB) absorption and evolution of the electron distribution function (EDF) in a wide laser intensity range (10;{12}-10;{17} W/cm;{2}) have been studied systematically by a two velocity-dimension Fokker-Planck code. It is found that Langdon's IB operator overestimates the absorption rate at high laser intensity, consequently with an overdistorted non-Maxwellian EDF. According to the small anisotropy of EDF in the oscillation frame, we introduce an IB operator which is similar to Langdon's but without the low laser intensity limit. This operator is appropriate for self-consistently tackling the nonlinear effects of high laser intensity as well as non-Maxwellian EDF. Particularly, our operator is capable of treating IB absorption properly in the indirect and direct-drive inertial confinement fusion schemes with the National Ignition Facility and Laser MegaJoule laser parameters at focused laser intensity beyond 10;{15} W/cm;{2} . PMID- 20365083 TI - Direct density measurement of shock-compressed iron using hard x rays generated by a short laser pulse. AB - We present the application of short-pulse laser-driven hard x rays (>40 keV) for the direct density measurement of iron compressed by a laser-driven shock. By using an on-shot calibration of the spectral absorption, we are able to obtain line densities with 5%-10% precision, although the x-ray source is not monochromatic. We also discuss possibilities for increasing the precision, which would be an improvement for equation of state measurements. PMID- 20365084 TI - Effect of external drive on strongly coupled Yukawa systems: a nonequilibrium molecular dynamics study. AB - Using nonequilibrium molecular dynamics (MD) simulations behavior of three dimensional (3D) Yukawa system has been studied in the presence of a small amplitude drive along one direction (say z[over ] ). This drive has the general form V=V_{0} cos(k_{L}z)Theta(t-t_{0}) , where Theta(t-t_{0}) is a Heaviside step function in time at t=t_{0} and k_{L}=2pi/L , L being the size of the system; V0 is considered small compared to average interparticle potential energy. In particular, a 3D equilibrated Yukawa crystal (bcc) near solid-liquid transition is subjected to an external drive at times t> or =t_{0} at the largest possible scale. For a given k_{L} it is observed that there exists a critical amplitude (V_{0};{c}) of the external drive below which the crystalline order is preserved and above which (V_{0}> or =V_{0};{c}) the transition from bcc to strongly coupled Yukawa liquid is observed. This critical amplitude (V_{0};{c}) is sensitive to the location of the Yukawa solid in the (kappa,Gamma) phase space. Various signatures of melting, transients, and steady state in the presence of this drive are elucidated using extensive MD diagnostics such as loss of long range crystalline order, change in diffusion from subnormal to normal, and the fall of transversal shear peak in the Fourier transform of the velocity autocorrelation function. The mechanism of heating in the transient state is attributed to the local heating of the system where the forces are maximum. It is shown that these local hot regions dissipate heat into surrounding regions ultimately leading to a uniform temperature throughout the system. Ion streaming due to external field has been neglected. PMID- 20365085 TI - Cavity equations for a positive- or negative-refraction-index material with electric and magnetic nonlinearities. AB - We study evolution equations for electric and magnetic field amplitudes in a ring cavity with plane mirrors. The cavity is filled with a positive or negative refraction-index material with third-order effective electric and magnetic nonlinearities. Two coupled nonlinear equations for the electric and magnetic amplitudes are obtained. We prove that the description can be reduced to one Lugiato-Lefever equation with generalized coefficients. A stability analysis of the homogeneous solution, complemented with numerical integration, shows that any combination of the parameters should correspond to one of three characteristic behaviors. PMID- 20365086 TI - Stationary shocks in periodic highly nonlinear granular chains. AB - We study the existence of stationary shock waves in uniform and periodic heterogeneous highly nonlinear granular chains governed by a power-law contact interaction, comparing discrete and continuum approaches, as well as experiments. We report the presence of quasisteady shock fronts without the need for dissipative effects. When viscous effects are neglected, the structure of the leading front appears to be solely the result of dispersive effects related to the lattice wave dispersion and, for heterogeneous bead chains, to the impedance mismatch between material domains. We report analytically and numerically the shock-width scaling with the variation in the particles periodicity (cell size) and compare the obtained results with experiments. We check the state (-) behind the shock front via quasistatic compression analysis and report a very good agreement between theory and numerical data. PMID- 20365087 TI - Calculation of coupled secular oscillation frequencies and axial secular frequency in a nonlinear ion trap by a homotopy method. AB - In this paper the homotopy perturbation method is used for calculation of the frequencies of the coupled secular oscillations and axial secular frequencies of a nonlinear ion trap. The motion of the ion in a rapidly oscillating field is transformed to the motion in an effective potential. The equations of ion motion in the effective potential are in the form of a Duffing-like equation. The homotopy perturbation method is used for solving the resulted system of coupled nonlinear differential equations and the resulted axial equation for obtaining the expressions for ion secular frequencies as a function of nonlinear field parameters and amplitudes of oscillations. The calculated axial secular frequencies are compared with the results of Lindstedt-Poincare method and the exact results. PMID- 20365088 TI - Statistics of the performance of time reversal in a lossy reverberating medium. AB - It has been proposed [J. De Rosny, Ph.D. thesis, Universite Paris VI, 2000] that the performance of time reversal at recreating a coherent pulse in a strongly reverberating medium is directly proportional to the number of resonant modes M actively taking part at the transmission of energy. This idea is here tested against experimental results showing that as soon as losses are taken into account, the quality of the focused pulse is a sublinear function of M leading to a saturation phenomenon that was previously unacknowledged. This is here proven to be caused by mutual coupling between lossy resonant modes, thanks to a statistical modal description of the transmission of signals through the medium. Closed-form relationships are proposed for the first two moments of the pulse signal-to-noise ratio linking them to the occupied bandwidth, the number of active modes, and the degree of resonance of the medium. These formulas, supported by experimental and numerical results, prove that the performance of time reversal can be affected by a strong statistical dispersion. The proposed analysis also predicts that time reversal is a self-averaging process when applied to a reverberating medium, thus, allowing the use of models developed in an ensemble-average framework. PMID- 20365089 TI - General framework for multiple scattering of polarized waves including anisotropies and Berry phase. AB - We develop a framework for the multiple scattering of a polarized wave. We consider particles with spin propagating in a medium filled with scatterers. We write the amplitudes of each spin eigenstate in a local mobile frame. One of the axes is in the direction of propagation of the particle. We use this representation to define a directional Green's operator of the homogeneous medium and also to write the spin-dependent scattering amplitudes. We show that this representation reveals a Berry phase. We establish a generalized Green-Dyson equation for the multiple-scattering problem in this framework. We show that the generalized Green-Dyson equation can be solved by linear algebra if one uses a representation of the rotations based on Wigner D matrices. The properties of light scattering are retrieved if we use spin 1 particles. Our theory allows to take into account several kinds of anisotropies such as circular or linear dichroism and birefringence, Faraday effects, and Mie scattering within the same formalism. Several anisotropies can be present at the same time. PMID- 20365090 TI - Lattice Boltzmann scheme for mixture modeling: analysis of the continuum diffusion regimes recovering Maxwell-Stefan model and incompressible Navier Stokes equations. AB - A finite difference lattice Boltzmann scheme for homogeneous mixture modeling, which recovers Maxwell-Stefan diffusion model in the continuum limit, without the restriction of the mixture-averaged diffusion approximation, was recently proposed [P. Asinari, Phys. Rev. E 77, 056706 (2008)]. The theoretical basis is the Bhatnagar-Gross-Krook-type kinetic model for gas mixtures [P. Andries, K. Aoki, and B. Perthame, J. Stat. Phys. 106, 993 (2002)]. In the present paper, the recovered macroscopic equations in the continuum limit are systematically investigated by varying the ratio between the characteristic diffusion speed and the characteristic barycentric speed. It comes out that the diffusion speed must be at least one order of magnitude (in terms of Knudsen number) smaller than the barycentric speed, in order to recover the Navier-Stokes equations for mixtures in the incompressible limit. Some further numerical tests are also reported. In particular, (1) the solvent and dilute test cases are considered, because they are limiting cases in which the Maxwell-Stefan model reduces automatically to Fickian cases. Moreover, (2) some tests based on the Stefan diffusion tube are reported for proving the complete capabilities of the proposed scheme in solving Maxwell-Stefan diffusion problems. The proposed scheme agrees well with the expected theoretical results. PMID- 20365091 TI - Spectral element method for band structures of three-dimensional anisotropic photonic crystals. AB - A spectral element method (SEM) is introduced for accurate calculation of band structures of three-dimensional anisotropic photonic crystals. The method is based on the finite-element framework with curvilinear hexahedral elements. Gauss Lobatto-Legendre polynomials are used to construct the basis functions. In order to suppress spurious modes, mixed-order vector basis functions are employed and the Bloch periodic boundary condition is imposed into the basis functions with tangential components at the boundary by multiplying a Bloch phase factor. The fields and coordinates in the curvilinear hexahedral elements are mapped to the reference domain by covariant mapping, which preserves the continuity of tangential components of the field. Numerical results show that the SEM has exponential convergence for both square-lattice and triangular-lattice photonic crystals. The sampling density as small as 3.4 points per wavelength can achieve accuracy as high as 99.9%. The band structures of several modified woodpile photonic crystals are calculated by using the SEM. PMID- 20365092 TI - Microcanonical replica exchange molecular dynamics simulation of proteins. AB - We present microcanonical replica exchange molecular dynamics simulations as an alternative to canonical ones. Its advantage is the easily tunable high acceptance rate for replica exchange. We present the theory, comment on its actual implementation, and demonstrate its application for a common test case, the trp-cage protein. PMID- 20365093 TI - Event-chain Monte Carlo algorithms for hard-sphere systems. AB - In this paper we present the event-chain algorithms, which are fast Markov-chain Monte Carlo methods for hard spheres and related systems. In a single move of these rejection-free methods, an arbitrarily long chain of particles is displaced, and long-range coherent motion can be induced. Numerical simulations show that event-chain algorithms clearly outperform the conventional Metropolis method. Irreversible versions of the algorithms, which violate detailed balance, improve the speed of the method even further. We also compare our method with a recent implementations of the molecular-dynamics algorithm. PMID- 20365094 TI - Efficient uncertainty minimization for fuzzy spectral clustering. AB - Spectral clustering uses the global information embedded in eigenvectors of an inter-item similarity matrix to correctly identify clusters of irregular shape, an ability lacking in commonly used approaches such as k -means and agglomerative clustering. However, traditional spectral clustering partitions items into hard clusters, and the ability to instead generate fuzzy item assignments would be advantageous for the growing class of domains in which cluster overlap and uncertainty are important. Korenblum and Shalloway [Phys. Rev. E 67, 056704 (2003)] extended spectral clustering to fuzzy clustering by introducing the principle of uncertainty minimization. However, this posed a challenging nonconvex global optimization problem that they solved by a brute-force technique unlikely to scale to data sets having more than O(10;{2}) items. Here we develop a method for solving the minimization problem, which can handle data sets at least two orders of magnitude larger. In doing so, we elucidate the underlying structure of uncertainty minimization using multiple geometric representations. This enables us to show how fuzzy spectral clustering using uncertainty minimization is related to and generalizes clustering motivated by perturbative analysis of almost-block-diagonal matrices. Uncertainty minimization can be applied to a wide variety of existing hard spectral clustering approaches, thus transforming them to fuzzy methods. PMID- 20365095 TI - Strengths and weaknesses of parallel tempering. AB - Parallel tempering, also known as replica exchange Monte Carlo, is studied in the context of two simple free-energy landscapes. The first is a double-well potential defined by two macrostates separated by a barrier. The second is a "golf course" potential defined by microstates having two possible energies with exponentially more high-energy states than low-energy states. The equilibration time for replica exchange is analyzed for both systems. For the double-well system, parallel tempering with a number of replicas that scales as the square root of the barrier height yields exponential speedup of the equilibration time. On the other hand, replica exchange yields only marginal speedup for the golf course system. For the double-well system, the free-energy difference between the two wells has a large effect on the equilibration time. Nearly degenerate wells equilibrate much more slowly than strongly asymmetric wells. It is proposed that this difference in equilibration time may lead to a bias in measuring overlaps in spin glasses. These examples illustrate the strengths and weaknesses of replica exchange and may serve as a guide for understanding and improving the method in various applications. PMID- 20365096 TI - Distribution for the number of coauthors. AB - We study the coauthorship distribution by analyzing the number of coauthors on each paper published in Physical Review Letters and Physical Review for the last decade. We propose that the structure of the distribution can be understood as the result of a two-parameter Poisson process. We develop a dynamic model of dual mechanisms to simulate the personal and group collaborations. In this model, the single-author papers are portrayed as a leftover from the collaboration process. We also comment on the huge collaborations involving hundreds of coauthors. PMID- 20365097 TI - Temporal structure and gain-loss asymmetry for real and artificial stock indices. AB - Previous research has shown that for stock indices, the most likely time until a return of a particular size has been observed is longer for gains than for losses. We demonstrate that this so-called gain-loss asymmetry vanishes if the temporal dependence structure is destroyed by scrambling the time series. We also show that an artificial index constructed by a simple average of a number of individual stocks display gain-loss asymmetry-this allows us to explicitly analyze the dependence between the index constituents. We consider mutual information and correlation-based measures and show that the stock returns indeed have a higher degree of dependence in times of market downturns than upturns. PMID- 20365098 TI - Time-delayed reaction-diffusion fronts. AB - A time-delayed second-order approximation for the front speed in reaction dispersion systems was obtained by Fort and Mendez [Phys. Rev. Lett. 82, 867 (1999)]. Here we show that taking proper care of the effect of the time delay on the reactive process yields a different evolution equation and, therefore, an alternate equation for the front speed. We apply the new equation to the Neolithic transition. For this application the new equation yields speeds about 10% slower than the previous one. PMID- 20365099 TI - Wavelet phase synchronization and chaoticity. AB - It has been shown that the so-called "wavelet phase" (or "time-scale") synchronization of chaotic signals is actually synchronization of smoothed functions with reduced chaotic fluctuations. This fact is based on the representation of the wavelet transform with the Morlet wavelet as a solution of the Cauchy problem for a simple diffusion equation with initial condition in a form of harmonic function modulated by a given signal. The topological background of the resulting effect is discussed. It is argued that the wavelet phase synchronization provides information about the synchronization of an averaged motion described by bounding tori instead of the fine-level classical chaotic phase synchronization. PMID- 20365100 TI - Dependence of intermittency scaling on threshold in chaotic systems. AB - Numerical and experimental investigations of intermittency in chaotic systems often lead to claims of universal classes based on the scaling of the average length of the laminar phase with parameter variation. We demonstrate that the scaling in general depends on the choice of the threshold used to define a proper laminar region in the phase space. For sufficiently large values of the threshold, the scaling exponent tends to converge but significant fluctuations can occur particularly for continuous-time systems. Insights into the dependence can be obtained using the idea of Poincare recurrence. PMID- 20365101 TI - True and quasi-long-range order in the generalized q-state clock model. AB - From consideration of the order-parameter distribution, we propose an observable which makes a clear distinction between true and quasi-long-range orders in the two-dimensional generalized q-state clock model. Measuring this quantity by Monte Carlo simulations for q=8, we construct a phase diagram and identify critical properties across the phase-separation lines among the true long-range order, quasi-long-range order, and disorder. Our result supports the theoretical prediction that there appears a discontinuous order-disorder transition as soon as the two phase-separation lines merge. PMID- 20365102 TI - Signal acquisition via polarization modulation in single photon sources. AB - A simple model system is introduced for demonstrating how a single photon source might be used to transduce classical analog information. The theoretical scheme results in measurements of analog source samples that are (i) quantized in the sense of analog-to-digital conversion and (ii) corrupted by random noise that is solely due to the quantum uncertainty in detecting the polarization state of each photon. This noise is unavoidable if more than 1 bit per sample is to be transmitted and we show how it may be exploited in a manner inspired by suprathreshold stochastic resonance. The system is analyzed information theoretically, as it can be modeled as a noisy optical communication channel, although unlike classical Poisson channels, the detector's photon statistics are binomial. Previous results on binomial channels are adapted to demonstrate numerically that the classical information capacity, and thus the accuracy of the transduction, increases logarithmically with the square root of the number of photons, N. Although the capacity is shown to be reduced when an additional detector nonideality is present, the logarithmic increase with N remains. PMID- 20365103 TI - Energy landscape and phase transitions in the self-gravitating ring model. AB - We apply a recently proposed criterion for the existence of phase transitions, which is based on the properties of the saddles of the energy landscape, to a simplified model of a system with gravitational interactions referred to as the self-gravitating ring model. We show analytically that the criterion correctly singles out the phase transition between a homogeneous and a clustered phase and also suggests the presence of another phase transition not previously known. On the basis of the properties of the energy landscape we conjecture on the nature of the latter transition. PMID- 20365104 TI - Ideal glass transition in a simple two-dimensional lattice model. AB - We present a simple lattice model showing a glassy behavior. R matrix analysis predicts critical termination of the supercooled fluid branch at density rho(g)=0.1717. This prediction is confirmed by dynamical numerical simulations, showing power-law divergences of relaxation time tau1/2, as well as the four susceptibility chi4 peak's location and height exactly at the predicted density. The power-law divergence of chi4 continues up to chi4 as high as 10(4). Finite size scaling study reveals the divergence of the correlation length accompanying the transition. PMID- 20365105 TI - Sliding through a superlight granular medium. AB - We explore the penetration dynamics of an intruder in a granular medium composed of expanded polystyrene spherical particles. Three features distinguish our experiment from others studied so far in granular physics: (a) the impact is horizontal, decoupling the effects of gravity and the drag force; (b) the density of the intruder rho(i) is up to 350 times larger than the density of the granular medium rho(m); and (c) the way the intruder moves through the material, sliding at the bottom of the column with small friction. Under these conditions we find that the final penetration D scales with (rho(i)/rho(m)) and the drag force Fd and D saturate with the height of the granular bed. PMID- 20365106 TI - Shear zone refraction and deflection in layered granular materials. AB - Refraction and deflection of shear zones in layered granular materials were studied experimentally and numerically. We show that (i) according to a recent theoretical prediction [T. Unger, Phys. Rev. Lett. 98, 018301 (2007)] shear zones refract in layered systems in analogy with light refraction, (ii) zone refraction obeys Snell's law known from geometric optics, and (iii) under natural pressure conditions (i.e., in the presence of gravity) the zone can also be deflected by the interface, so that the deformation of the high friction material is avoided. PMID- 20365107 TI - Stress correlations in granular materials: an entropic formulation. AB - We study the response of dry granular materials to external stress using experiment, simulation, and theory. We derive a Ginzburg-Landau functional that enforces mechanical stability and positivity of contact forces. In this framework, the elastic moduli depend only on the applied stress. A combination of this feature and the positivity constraint leads to stress correlations whose shape and magnitude are extremely sensitive to the nature of the applied stress. The predictions from the theory describe the stress correlations for both simulations and experiments semiquantitatively. PMID- 20365108 TI - Particle kinematics in a dilute, three-dimensional, vibration-fluidized granular medium. AB - We report an experimental study of particle kinematics in a three-dimensional system of inelastic spheres fluidized by intense vibration. The motion of particles in the interior of the medium is tracked by high-speed video imaging, yielding a spatially resolved measurement of the velocity distribution. The distribution is wider than a Gaussian and broadens continuously with increasing volume fraction. The deviations from a Gaussian distribution for this boundary driven system are different in sign and larger in magnitude than predictions for homogeneously driven systems. We also find correlations between velocity components which grow with increasing volume fraction. PMID- 20365109 TI - Viscosity-dependent liquid slip at molecularly smooth hydrophobic surfaces. AB - Colloidal probe atomic force microscopy is used to study the slip behavior of 18 Newtonian liquids from two homologous series, the n-alkanes and n-alcohols, at molecularly smooth hydrophobic n-hexadecyltrichlorosilane coated surfaces. We find that the slip behavior is governed by the bulk viscosity eta of the liquid, specifically, the slip length b approximately etax with x approximately 0.33. Additionally, the slip length was found to be shear rate independent, validating the use of Vinogradova slip theory in this work. PMID- 20365110 TI - Patterning-induced surface chirality and modulation of director twist in a nematic cell. AB - A substrate coated with a polyimide alignment layer is scribed bidirectionally with the stylus of an atomic force microscope to create an easy axis for liquid crystal orientation. The resulting noncentrosymmetric topography breaks two dimensional inversion symmetry and results in a spatial amplitude modulation of an imposed twisted nematic state. This is observed optically as spatially periodic light and dark stripes. When the alignment layer is scribed unidirectionally the centrosymmetric topography maintains inversion symmetry, and no stripes are observed. The appearance of the twist modulation is consistent with a chiral term in the free energy. PMID- 20365111 TI - Nonlinear dynamics of cell orientation. AB - The nonlinear dependence of cellular orientation on an external, time-varying stress field determines the distribution of orientations in the presence of noise and the characteristic time, tauc, for the cell to reach its steady-state orientation. The short, local cytoskeletal relaxation time distinguishes between high-frequency (nearly perpendicular) and low-frequency (random or parallel) orientations. However, tauc is determined by the much longer, orientational relaxation time. This behavior is related to experiments for which we predict the angle and characteristic time as a function of frequency. PMID- 20365112 TI - Phase diagram of the Weeks-Chandler-Andersen potential from very low to high temperatures and pressures. AB - A combination of two molecular simulation algorithms has been used to determine the solid-liquid coexistence of the Weeks-Chandler-Andersen (WCA) fluid from low temperatures up to very high temperatures. Values are reported for the coexistence pressure, temperature, energy, enthalpy change, and densities of both the liquid and solid phases. At very high temperatures, the coexistence pressure approaches the same 12th-power soft-sphere asymptote as the 12-6 Lennard-Jones potential. However, in contrast to the Lennard-Jones potential, which shows a discontinuity of pressure at low temperatures, the coexistence pressure of the WCA potential approaches the zero-temperature limit. Empirical relationships are determined to accurately reproduce the coexistence pressure and both solid and liquid phase densities from near zero temperature to very high temperatures. The simulation data are used to improve the accuracy of a WCA equation of state. The validity of common melting and freezing rules is tested. PMID- 20365113 TI - Langevin equation approach to diffusion magnetic resonance imaging. AB - The normal phase diffusion problem in magnetic resonance imaging (MRI) is treated by means of the Langevin equation for the phase variable using only the properties of the characteristic function of Gaussian random variables. The calculation may be simply extended to anomalous diffusion using a fractional generalization of the Langevin equation proposed by Lutz [E. Lutz, Phys. Rev. E 64, 051106 (2001)] pertaining to the fractional Brownian motion of a free particle coupled to a fractal heat bath. The results compare favorably with diffusion-weighted experiments acquired in human neuronal tissue using a 3 T MRI scanner. PMID- 20365114 TI - Absence of the discontinuous transition in the one-dimensional triplet creation model. AB - Although Hinrichsen in his unpublished work theoretically rebutted the possibility of the discontinuous transition in one-dimensional nonequilibrium systems unless there are additional conservation laws, long-range interactions, macroscopic currents, or special boundary conditions, we have recently observed the resurrection of the claim that the triplet creation (TC) model introduced by Dickman and Tome [Phys. Rev. A 44, 4833 (1991)] would show the discontinuous transition. By extensive simulations, however, we find that the one-dimensional TC does belong to the directed percolation universality class even for larger diffusion constant than the suggested tricritical point in the literature. Furthermore, we find that the phase boundary is well described by the crossover from the mean field to the directed percolation, which supports the claim that the one-dimensional TC does not exhibit a discontinuous transition. PMID- 20365115 TI - Bounded rationality leads to equilibrium of public goods games. AB - In this work, we introduce a degree of rationality to the public goods games in which players can determine whether or not to participate, and with it a new mechanism has been established. Existence of the bounded rationality would lead to a new equilibrium which differs from the Nash equilibrium and qualitatively explains the fundamental role of loners' payoff for maintaining cooperation. Meanwhile, it is shown how the potential strategy influences the players' decision. Finally, we explicitly demonstrate a rock-scissors-paper dynamics which is a consequence of this model. PMID- 20365116 TI - Discontinuous nonequilibrium phase transitions in a nonlinearly pulse-coupled excitable lattice model. AB - We study a modified version of the stochastic susceptible-infected-refractory susceptible (SIRS) model by employing a nonlinear (exponential) reinforcement in the contagion rate and no diffusion. We run simulations for complete and random graphs as well as d-dimensional hypercubic lattices (for d=3,2,1). For weak nonlinearity, a continuous nonequilibrium phase transition between an absorbing and an active phase is obtained, such as in the usual stochastic SIRS model [Joo and Lebowitz, Phys. Rev. E 70, 036114 (2004)]. However, for strong nonlinearity, the nonequilibrium transition between the two phases can be discontinuous for d>or=2, which is confirmed by well-characterized hysteresis cycles and bistability. Analytical mean-field results correctly predict the overall structure of the phase diagram. Furthermore, contrary to what was observed in a model of phase-coupled stochastic oscillators with a similar nonlinearity in the coupling [Wood, Phys. Rev. Lett. 96, 145701 (2006)], we did not find a transition to a stable (partially) synchronized state in our nonlinearly pulse-coupled excitable elements. For long enough refractory times and high enough nonlinearity, however, the system can exhibit collective excitability and unstable stochastic oscillations. PMID- 20365117 TI - Intensity statistics of random signals in Gaussian noise. AB - The intensity statistics of random signals in the presence of Gaussian noise is obtained by considering the model of a random signal plus a random phasor sum. The additive Gaussian noise is shown to result in a Bessel transform of the probability density of signal intensity. The transformation of the intensity statistics can generally be applied to mixtures of independent random signals, one of which being a complex-valued Gaussian random process. It is used to retrieve intensity statistics of microwave pulsed transmission from Gaussian noise at long time delays. PMID- 20365118 TI - One-component plasma of point charges and of charged rods. AB - An approximate theory is developed to describe the properties of mobile particles with extended charge distributions in the presence of a neutralizing fixed background charge. Long-wavelength fluctuations of the electric potential are handled within a variational perturbation approximation, and the short-wavelength fluctuations are handled within a cumulant (fugacity) expansion. The distinct treatment of these two contributions to the free energy enables the theory to provide quantitative predictions for the properties of these systems from the weak- to the strong-coupling regimes. With this theory, we study three different variations in the classical one-component plasma model: a plasma of point charges, a plasma of particles consisting of 8 linearly bonded point charges (8 mer), and a plasma of line charges. The theory was found to agree well with the available computer simulation data for the electrostatic interaction energy of these systems for all values of the plasma coupling parameter examined ( Gamma=0 to 400). In addition, we find that both the 8-mer rod and the line charge systems form a strongly ordered nematic phase, which is entirely driven by electrostatic interactions. The nematic phase only exists within a finite range of lengths of the charged particles. If the particles are too short or too long, the nematic phase does not appear. Finally, we find that the nematic phase is stable over a broader range of conditions for the line charge system than for the 8-mer rod system; consequently, the phase behavior of the one-component plasma is sensitive to the manner in which the charge is distributed on the particles. PMID- 20365119 TI - Hierarchical models of rigidity percolation. AB - We introduce models of generic rigidity percolation in two dimensions on hierarchical networks and solve them exactly by means of a renormalization transformation. We then study how the possibility for the network to self organize in order to avoid stressed bonds may change the phase diagram. In contrast to what happens on random graphs and in some recent numerical studies at zero temperature, we do not find a true intermediate phase separating the usual rigid and floppy ones. PMID- 20365120 TI - Exact energy spectrum of a two-temperature kinetic Ising model. AB - We develop the exact energy spectrum for a two-temperature kinetic Ising spin chain and its dual reaction-diffusion system with spatially alternating pair annihilation and creation rates. We also discuss the symmetries of the system pseudo-Hamiltonian and their role in developing a general solution. The surprisingly simple form for the eigenvalues leads to interesting physical consequences and to a possible numerical analysis of the dynamical properties of the system. PMID- 20365121 TI - Hard-sphere crystallization gets rarer with increasing dimension. AB - We recently found that crystallization of monodisperse hard spheres from the bulk fluid faces a much higher free-energy barrier in four than in three dimensions at equivalent supersaturation, due to the increased geometrical frustration between the simplex-based fluid order and the crystal [J. A. van Meel, D. Frenkel, and P. Charbonneau, Phys. Rev. E 79, 030201(R) (2009)]. Here, we analyze the microscopic contributions to the fluid-crystal interfacial free energy to understand how the barrier to crystallization changes with dimension. We find the barrier to grow with dimension and we identify the role of polydispersity in preventing crystal formation. The increased fluid stability allows us to study the jamming behavior in four, five, and six dimensions and to compare our observations with two recent theories [C. Song, P. Wang, and H. A. Makse, Nature (London) 453, 629 (2008); G. Parisi and F. Zamponi, Rev. Mod. Phys. (to be published)]. PMID- 20365122 TI - Distinct scalings for mean first-passage time of random walks on scale-free networks with the same degree sequence. AB - In general, the power-law degree distribution has profound influence on various dynamical processes defined on scale-free networks. In this paper, we will show that power-law degree distribution alone does not suffice to characterize the behavior of trapping problems on scale-free networks, which is an integral major theme of interest for random walks in the presence of an immobile perfect absorber. In order to achieve this goal, we study random walks on a family of one parameter (denoted by q) scale-free networks with identical degree sequence for the full range of parameter q, in which a trap is located at a fixed site. We obtain analytically or numerically the mean first-passage time (MFPT) for the trapping issue. In the limit of large network order (number of nodes), for the whole class of networks, the MFPT increases asymptotically as a power-law function of network order with the exponent obviously different for different parameter q, which suggests that power-law degree distribution itself is not sufficient to characterize the scaling behavior of MFPT for random walks at least trapping problem, performed on scale-free networks. PMID- 20365123 TI - Simulating stochastic dynamics using large time steps. AB - We present an approach to investigate the long-time stochastic dynamics of multidimensional classical systems, in contact with a heat bath. When the potential energy landscape is rugged, the kinetics displays a decoupling of short and long-time scales and both molecular dynamics or Monte Carlo (MC) simulations are generally inefficient. Using a field theoretic approach, we perform analytically the average over the short-time stochastic fluctuations. This way, we obtain an effective theory, which generates the same long-time dynamics of the original theory, but has a lower time-resolution power. Such an approach is used to develop an improved version of the MC algorithm, which is particularly suitable to investigate the dynamics of rare conformational transitions. In the specific case of molecular systems at room temperature, we show that elementary integration time steps used to simulate the effective theory can be chosen a factor approximately 100 larger than those used in the original theory. Our results are illustrated and tested on a simple system, characterized by a rugged energy landscape. PMID- 20365124 TI - Einstein-Helfand form for transport coefficients from coarse-grained descriptions. AB - We revisit the statistical mechanics problem of coarse-graining a system that at a detailed level is described by an already coarse-grained dynamics. The dynamics at the more detailed level is described by a Fokker-Planck equation instead of the Liouville equation. The method generalizes Zwanzig theory of projection operators and produces a friction matrix in terms of a correlation function that is not manifestly an autocorrelation. Therefore, from this expression, it is not obvious that the friction matrix is definite positive. We show that the Green Kubo transport matrix can be written in the Einstein-Helfand form, which is manifestly positive definite. We also discuss the role of time reversal and detailed balance in the coarse-grained dynamics. PMID- 20365125 TI - Characterizing steady-state and transient properties of reaction-diffusion systems. AB - In the past, the study of reaction-diffusion systems has greatly contributed to our understanding of the behavior of many-body systems far from equilibrium. In this paper, we aim at characterizing the properties of diffusion-limited reactions both in their steady states and out of stationarity. Many reaction diffusion systems have the peculiarity that microscopic reversibility is broken such that their transient behavior cannot be investigated through the study of most of the observables discussed in the literature. For this reason, we analyze the transient properties of reaction-diffusion systems through a specific work observable that remains well defined even in the absence of microscopic reversibility and that obeys an exact detailed fluctuation relation in cases where detailed balance is fulfilled. We thereby drive the systems out of their nonequilibrium steady states through time-dependent reaction rates. Using a numerical exact method and computer simulations, we analyze fluctuation ratios of the probability distributions obtained during the forward and reversed processes. We show that the underlying microscopic dynamics gives rise to peculiarities in the configuration-space trajectories, thereby, yielding prominent features in the fluctuation ratios. PMID- 20365126 TI - Molecular wires acting as quantum heat ratchets. AB - We explore heat transfer in molecular junctions between two leads in the absence of a finite net thermal bias. The application of an unbiased time-periodic temperature modulation of the leads entails a dynamical breaking of reflection symmetry, such that a directed heat current may emerge (ratchet effect). In particular, we consider two cases of adiabatically slow driving, namely, (i) periodic temperature modulation of only one lead and (ii) temperature modulation of both leads with an ac driving that contains a second harmonic, thus, generating harmonic mixing. Both scenarios yield sizable directed heat currents, which should be detectable with present techniques. Adding a static thermal bias allows one to compute the heat current-thermal load characteristics, which includes the ratchet effect of negative thermal bias with positive-valued heat flow against the thermal bias, up to the thermal stop load. The ratchet heat flow in turn generates also an electric current. An applied electric stop voltage, yielding effective zero electric current flow, then mimics a solely heat-ratchet induced thermopower ("ratchet Seebeck effect"), although no net thermal bias is acting. Moreover, we find that the relative phase between the two harmonics in scenario (ii) enables steering the net heat current into a direction of choice. PMID- 20365127 TI - Ground states and formal duality relations in the Gaussian core model. AB - We study dimensional trends in ground states for soft-matter systems. Specifically, using a high-dimensional version of Parrinello-Rahman dynamics, we investigate the behavior of the Gaussian core model in up to eight dimensions. The results include unexpected geometric structures, with surprising anisotropy as well as formal duality relations. These duality relations suggest that the Gaussian core model possesses unexplored symmetries, and they have implications for a broad range of soft-core potentials. PMID- 20365128 TI - Record events in growing populations: universality, correlation, and aging. AB - This paper studies the occurrence of record events in score populations which grow stochastically in time. In Renyi's basic record model, a population of independent and identically distributed (i.i.d.) random scores grows deterministically--a single new score being added at each time step. Renyi's record theorem asserts that the resulting record events are independent, and that their occurrence probabilities decrease harmonically in time. Moreover, Renyi's result is universal--being independent of the distribution of the i.i.d. random scores. This paper considers an arbitrary stochastic growth of the score population--allowing the number of the i.i.d. random scores added at each time step to follow arbitrary stochastic dynamics. Exploring the stochastic growth model we: (i) establish a general analog of Renyi's record theorem; (ii) show that universality with respect to the distribution of the i.i.d. random scores is maintained; (iii) compute the distribution of the waiting times for record events; (iv) analyze the dependencies/independencies of the record events; and (v) analyze the aging/stationarity of the record events. PMID- 20365129 TI - Data-driven approach to decomposing complex enzyme kinetics with surrogate models. AB - The temporal autocorrelation (AC) function associated with monitoring order parameters characterizing conformational fluctuations of an enzyme is analyzed using a collection of surrogate models. The surrogates considered are phenomenological stochastic differential equation (SDE) models. It is demonstrated how an ensemble of such surrogate models, each surrogate being calibrated from a single trajectory, indirectly contains information about unresolved conformational degrees of freedom. This ensemble can be used to construct complex temporal ACs associated with a "non-Markovian" process. The ensemble of surrogates approach allows researchers to consider models more flexible than a mixture of exponentials to describe relaxation times and at the same time gain physical information about the system. The relevance of this type of analysis to matching single-molecule experiments to computer simulations and how more complex stochastic processes can emerge from a mixture of simpler processes is also discussed. The ideas are illustrated on a toy SDE model and on molecular-dynamics simulations of the enzyme dihydrofolate reductase. PMID- 20365130 TI - Memory effects in recurrent and extreme events. AB - A dynamical approach to recurrent and extreme events is developed focusing on the role of correlations and memory in the structure of the probability distributions and their low-order moments. The procedure is illustrated on homogeneous first and second order Markov chains, non-Markovian and nonhomogeneous processes and deterministic dynamical systems. Substantial differences with classical statistical theory as applied to independent identically distributed random variables are identified. PMID- 20365131 TI - Another method to compute the thermodynamic Casimir force in lattice models. AB - We discuss a method that allows us to compute the thermodynamic Casimir force at a given temperature in lattice models by performing a single Monte Carlo simulation. It is analogous to the one used by de Forcrand and co-workers in the study of 't Hooft loops and the interface tension in SU(N) lattice gauge models in four dimensions. We test the method at the example of thin films in the XY universality class. In particular we simulate the improved two-component phi4 model on the simple cubic lattice. This allows us to compare with our previous study, where we have computed the Casimir force by numerically integrating energy densities over the inverse temperature. PMID- 20365132 TI - Survival probability of a subdiffusive particle in a d-dimensional sea of mobile traps. AB - We investigate the long-time behavior of the survival probability P(t) of a mobile particle in d-dimensional continuous Euclidean media doped with noninteracting mobile traps. The particle is strictly subdiffusive, implying that its mean-square displacement grows as tgamma' with 0or=2 we find that at late times the survival probability is that of the pure target problem (the problem where the particle remains immobile) in agreement with previous studies for the d=1 case. These decay laws remain invariant over the whole gamma range as opposed to the dynamical crossover observed for the case of a purely diffusive particle (gamma'=1) where, for gamma<2/(2+d) , the survival probability becomes that of the so-called trapping problem (the problem where the particle moves in a sea of static traps). This behavior implies that for sufficiently low values of gamma(gamma<2/(2+d)) the survival probability becomes singular in the limit gamma'-->1: trappinglike for gamma'=1 and targetlike for any gamma'<1. PMID- 20365133 TI - Discriminating between normal and anomalous random walks. AB - Commonly, normal diffusive behavior is characterized by a linear dependence of the second central moment on time, {x2(t) proportional t, while anomalous behavior is expected to show a different time dependence, x2(t) proportional t{delta} with delta<1 for subdiffusive and delta>1 for superdiffusive motions. Here we explore in details the fact that this kind of qualification, if applied straightforwardly, may be misleading: there are anomalous transport motions revealing perfectly "normal" diffusive character (x2(t) proportional t) yet being non-Markov and non-Gaussian in nature. We use recently developed framework of Monte Carlo simulations which incorporates anomalous diffusion statistics in time and space and creates trajectories of such an extended random walk. For special choice of stability indices describing statistics of waiting times and jump lengths, the ensemble analysis of anomalous diffusion is shown to hide temporal memory effects which can be properly detected only by examination of formal criteria of Markovianity (fulfillment of the Chapman-Kolmogorov equation). PMID- 20365134 TI - Molecular dynamics and analytical Langevin equation approach for the self diffusion constant of an anisotropic fluid. AB - We carried out a molecular-dynamics (MD) study of the self-diffusion tensor of a Lennard-Jones-type fluid, confined in a slit pore with attractive walls. We developed Bayesian equations, which modify the virtual layer sampling method proposed by Liu, Harder, and Berne (LHB) [P. Liu, E. Harder, and B. J. Berne, J. Phys. Chem. B 108, 6595 (2004)]. Additionally, we obtained an analytical solution for the corresponding nonhomogeneous Langevin equation. The expressions found for the mean-squared displacement in the layers contain naturally a modification due to the mean force in the transverse component in terms of the anisotropic diffusion constants and mean exit time. Instead of running a time consuming dual MD-Langevin simulation dynamics, as proposed by LHB, our expression was used to fit the MD data in the entire survival time interval not only for the parallel but also for the perpendicular direction. The only fitting parameter was the diffusion constant in each layer. PMID- 20365135 TI - Statistical mechanical analysis of the Kronecker channel model for multiple-input multiple-output wireless communication. AB - The Kronecker channel model of wireless communication is analyzed using statistical mechanics methods. In the model, spatial proximities among transmission/reception antennas are taken into account as certain correlation matrices, which generally yield nontrivial dependence among symbols to be estimated. This prevents accurate assessment of the communication performance by naively using a previously developed analytical scheme based on a matrix integration formula. In order to resolve this difficulty, we develop a formalism that can formally handle the correlations in Kronecker models based on the known scheme. Unfortunately, direct application of the developed scheme is, in general, practically difficult. However, the formalism is still useful, indicating that the effect of the correlations generally increase after the fourth order with respect to correlation strength. Therefore, the known analytical scheme offers a good approximation in performance evaluation when the correlation strength is sufficiently small. For a class of specific correlation, we show that the performance analysis can be mapped to the problem of one-dimensional spin systems in random fields, which can be investigated without approximation by the belief propagation algorithm. PMID- 20365136 TI - Nucleation stage with nonsteady growth of supercritical gas bubbles in a strongly supersaturated liquid solution and the effect of excluded volume. AB - An approach to the kinetics of barrier formation of supercritical gas bubbles in a strongly supersaturated liquid solution is presented. A common assumption of uniform reduction of a dissolved gas supersaturation in a liquid solution via stationary diffusion to nucleating gas bubbles is shown to be not applicable to the case of high gas supersaturations. The approach recognizes that the diffusion growth of supercritical bubbles at high gas supersaturation is essentially nonstationary. Nonstationary growth of an individual gas bubble is described by a self-similar solution of the diffusion equation which predicts a renormalized growth rate and thin highly nonuniform diffusion layer around the bubble. The depletion of a dissolved gas due to intake of gas molecules by the bubble occurs only within this thin layer. An integral equation for the total volume of an ensemble of supercritical gas bubbles within a liquid solution is derived. This equation describes the effect of excluding a total volume of the depleted diffusion layers around the growing bubbles nucleated at all previous moments of time until nucleation of new bubbles ceases due to elimination of the nondepleted volume of the solution. An analytical solution of this equation is found. The swelling of the liquid solution, the number of gas bubbles nucleated, the distribution function of bubbles in their sizes, and the mean radius of the bubbles are determined in their dependence on time. PMID- 20365137 TI - Multifractal analysis of light scattering-intensity fluctuations. AB - We provide a simple interpretation of non-Gaussian nature of the light scattering intensity fluctuations from an aging colloidal suspension of Laponite using the multiplicative cascade model, Markovian method, and volatility correlations. The cascade model and Markovian method enable us to reproduce most of recent empirical findings: long-range volatility correlations and non-Gaussian statistics of intensity fluctuations. We provide evidence that the intensity increments Deltax(tau)=I(t+tau)-I(t), upon different delay time scales tau, can be described as a Markovian process evolving in tau. Thus, the tau dependence of the probability density function p(Deltax,tau) on the delay time scale tau can be described by a Fokker-Planck equation. We also demonstrate how drift and diffusion coefficients in the Fokker-Planck equation can be estimated directly from the data. PMID- 20365138 TI - Universality classes of the absorbing state transition in a system with interacting static and diffusive populations. AB - In this work, we study the critical behavior of a one-dimensional model that mimics the propagation of an epidemic process mediated by a density of diffusive individuals which can infect a static population upon contact. We simulate the above model on linear chains to determine the critical density of the diffusive population, above which the system achieves a statistically stationary active state, as a function of two relevant parameters related to the average lifetimes of the diffusive and nondiffusive populations. A finite-size scaling analysis is employed to determine the order parameter and correlation length critical exponents. For high-recovery rates, the critical exponents are compatible with the usual directed percolation universality class. However, in the opposite regime of low-recovery rates, the diffusion is a relevant mechanism responsible for the propagation of the disease and the absorbing state phase transition is governed by a distinct set of critical exponents. PMID- 20365139 TI - Pairwise summation approximation of Casimir energy from first principles. AB - We obtain the pairwise summation approximation (PSA) of the Casimir energy from first principles in the soft dielectric and soft diamagnetic limit, this analysis let us find that the PSA is an asymptotic approximation of the Casimir energy valid for large distances between the objects. We also obtain the PSA for the electromagnetic coupling part of the Casimir energy, so we are able to complete the PSA limit for the first time for the complete electromagnetic field. PMID- 20365140 TI - Quantum optical thermodynamic machines: lasing as relaxation. AB - Motivated by the growing interest in the nanophysics and the field of quantum thermodynamics we study an open quantum system consisting of two spatially separated two-level atoms (spins) coupled to a quantum oscillator (resonator field mode). There is no external driving. The spins of different energy splittings are each linked to a heat bath with different temperature. We find that the temperature gradient imposed on the system together with the oscillator operating as a kind of work reservoir makes this system act as a thermodynamic machine, in particular, as a heat engine (laser). We analyze the properties of the resulting resonator field and of the engine functionality. For the latter problem we use recently developed definitions of heat flux and power as well as a test, in which the resulting field is used as an input for a heat pump. PMID- 20365141 TI - Quantum quenches in the Dicke model: statistics of the work done and of other observables. AB - We study the statistics of the work done in a zero temperature quench of the coupling constant in the Dicke model describing the interaction between an ensemble of two level systems and a single bosonic mode. When either the final or the initial coupling constants approach the critical coupling lambdac that separates the normal and superradiant phases of the system, the probability distribution of the work done displays singular behavior. The average work tends to diverge as the initial coupling parameter is brought closer to the critical value lambdac. In contrast, for quenches ending close to criticality, the distribution of work has finite moments but displays a sequence of edge singularities. This contrasting behavior is related to the difference between the processes of compression and expansion of a particle subject to a sudden change in its confining potential. We confirm this by studying in detail the time dependent statistics of other observables, such as the quadratures of the photons and the total occupation of the bosonic modes. PMID- 20365142 TI - Stiffness dependence of critical exponents of semiflexible polymer chains situated on two-dimensional compact fractals. AB - We present an exact and Monte Carlo renormalization group (MCRG) study of semiflexible polymer chains on an infinite family of the plane-filling (PF) fractals. The fractals are compact, that is, their fractal dimension df is equal to 2 for all members of the fractal family enumerated by the odd integer b(3C+D and 2A-->2C under a flow in two and three dimensions. Different densities of reactants A and B are fixed at both ends. For the reaction A+B , the concentration of reactants asymptotically decay in space as x-1/2 and x-3/4 in two dimensions and three dimensions, respectively. For 2A , it decays as log(x)/x in two dimensions. The decay of A+B is explained considering the effect of segregation of reactants in the isotropic case. The decay for 2A is explained by the marginal behavior of two-dimensional diffusion. A logarithmic divergence of the diffusion constant with system size is found in two dimensions. PMID- 20365144 TI - Exact calculation of the tortuosity in disordered linear pores in the Knudsen regime. AB - The squared reciprocal tortuosity kappa-2=D/D0 for linear diffusion on lattices and in pores in the Knudsen regime is calculated analytically for a large variety of disordered systems. Here, D0 and D are the self-diffusion coefficients of the smooth and the corresponding disordered system, respectively. To this end, a building-block principle is developed that composes the systems into substructures without cross correlations between them. It is shown how the solutions of the different building blocks can be combined to gain D/D0 for pores of high complexity from the geometrical properties of the systems, i.e., from the volumes of the different substructures. As a test, numerical simulations are performed that agree perfectly with the theory. PMID- 20365145 TI - Persistent memory of diffusing particles. AB - The variance of the advection-diffusion processes with variable coefficients is exactly decomposed as a sum of dispersion terms and memory terms consisting of correlations between velocity and initial positions. For random initial conditions, the memory terms quantify the departure of the preasymptotic variance from the time-linear diffusive behavior. For deterministic initial conditions, the memory terms account for the memory of the initial positions of the diffusing particles. Numerical simulations based on a global random walk algorithm show that the influence of the initial distribution of the cloud of particles is felt over hundreds of dimensionless times. In case of diffusion in random velocity fields with finite correlation range the particles forget the initial positions in the long-time limit and the variance is self-averaging, with clear tendency toward normal diffusion. PMID- 20365146 TI - Interacting molecular motors: efficiency and work fluctuations. AB - We investigate the model of "reversible ratchet" with interacting particles, presented by us earlier [F. Slanina, EPL 84, 50009 (2008)]. We further clarify the effect of efficiency enhancement due to interaction and show that it is of energetic origin, rather than a consequence of reduced fluctuations. We also show complicated structures emerging in the interaction and density dependence of the current and response function. The fluctuation properties of the work and input energy indicate in detail the far-from-equilibrium nature of the dynamics. PMID- 20365147 TI - Statistical mechanics of maximal independent sets. AB - The graph theoretic concept of maximal independent set arises in several practical problems in computer science as well as in game theory. A maximal independent set is defined by the set of occupied nodes that satisfy some packing and covering constraints. It is known that finding minimum and maximum-density maximal independent sets are hard optimization problems. In this paper, we use cavity method of statistical physics and Monte Carlo simulations to study the corresponding constraint satisfaction problem on random graphs. We obtain the entropy of maximal independent sets within the replica symmetric and one-step replica symmetry breaking frameworks, shedding light on the metric structure of the landscape of solutions and suggesting a class of possible algorithms. This is of particular relevance for the application to the study of strategic interactions in social and economic networks, where maximal independent sets correspond to pure Nash equilibria of a graphical game of public goods allocation. PMID- 20365148 TI - Local entropy in quasi-one-dimensional heat transport. AB - We study the nonequilibrium entropy of the heat transport problem by performing molecular dynamics simulations of a quasi-one-dimensional gas of hard disks in the steady state. The entropy density, flux, and production rate, associated with the entropy balance of the system, are obtained from the numerically measured velocity distributions, based on the kinetic theory analysis of the Boltzmann entropy. We obtain an equilibriumlike Clausius relation from the computer experiments which, in turn, fulfills the generalized Gibbs relation for spatially inhomogeneous states. PMID- 20365149 TI - Nonequilibrium phase transition in an exactly solvable driven Ising model with friction. AB - A driven Ising model with friction due to magnetic correlations was proposed by Kadau [Phys. Rev. Lett. 101, 137205 (2008)]. The nonequilibrium phase transition present in this system is investigated in detail using analytical methods as well as Monte Carlo simulations. In the limit of high driving velocities v the model shows mean-field behavior due to dimensional reduction and can be solved exactly for various geometries. The simulations are performed with three different single spin-flip rates: the common Metropolis and Glauber rates as well as a multiplicative rate. Due to the nonequilibrium nature of the model all rates lead to different critical temperatures at v>0, while the exact solution matches the multiplicative rate. Finally, the crossover from Ising to mean-field behavior as function of velocity and system size is analyzed in one and two dimensions. PMID- 20365150 TI - Experimental study of resonant activation in a noisy bistable vertical-cavity surface-emitting laser with strong periodic excitation. AB - An experimental evidence of the phenomenon of resonance activation (RA) in bistable semiconductor vertical-cavity surface-emitting laser (VCSEL) with a high level of internal noise under strong periodic excitation is presented. It is shown that the mean switching period (MSP) between polarization states passes through a minimum depending on the modulation frequency. From comparing frequency dependencies of the MSP and the coefficient of variation it is demonstrated for different conditions that resonance activation and stochastic resonance (SR) occur at different optimal values of the modulation frequency. The influence of the signal amplitude, the level of noise in VCSEL and asymmetry of bistable quasipotential are also experimentally studied. For large enough modulation amplitudes, RA and SR are accompanied by the phenomenon of the mean switching frequency locking. PMID- 20365151 TI - Existence of a dynamic compensation temperature of a mixed spin-2 and spin-5/2 Ising ferrimagnetic system in an oscillating field. AB - The magnetic properties of a nonequilibrium mixed spin-2 and spin-5/2 Ising ferrimagnetic system with a crystal-field interaction (D) in the presence of a time-varying magnetic field on a hexagonal lattice are studied by using the Glauber-type stochastic dynamics. The model system consists of two interpenetrating sublattices with sigma=2 and S=5/2. The Hamiltonian model includes intersublattice, intrasublattice, and crystal-field interactions. The intersublattice interaction is considered antiferromagnetic to have a simple but interesting model of a ferrimagnetic system. The set of mean-field dynamic equations is obtained by employing the Glauber transition rates. First, we investigate the time variations in average sublattice magnetizations to find the phases in the system, and the temperature dependence of the dynamic sublattice magnetizations to characterize the nature (continuous or discontinuous) of the phase transitions and to obtain the dynamic phase transition points. Then, we study the temperature dependence of the total magnetization to find the dynamic compensation points as well as to determine the type of behavior. We also investigate the effect of a crystal-field interaction and the exchange couplings between the nearest-neighbor pairs of spins on the compensation phenomenon and present the dynamic phase diagrams. According to values of Hamiltonian parameters, the paramagnetic, the nonmagnetic, and the four different ferrimagnetic fundamental phases, seven different mixed phases, and the compensation temperature, or the N-type behavior in the Neel classification nomenclature exist in the system. A comparison is made with the results of the available mixed spin Ising systems. PMID- 20365152 TI - Thermodynamic constraints on fluctuation phenomena. AB - The relationships among reversible Carnot cycles, the absence of perpetual motion machines, and the existence of a nondecreasing globally unique entropy function form the starting point of many textbook presentations of the foundations of thermodynamics. However, the thermal fluctuation phenomena associated with statistical mechanics has been argued to restrict the domain of validity of this basis of the second law of thermodynamics. Here we demonstrate that fluctuation phenomena can be incorporated into the traditional presentation, extending rather than restricting the domain of validity of the phenomenologically motivated second law. Consistency conditions lead to constraints upon the possible spectrum of thermal fluctuations. In a special case this uniquely selects the Gibbs canonical distribution and more generally incorporates the Tsallis distributions. No particular model of microscopic dynamics need be assumed. PMID- 20365153 TI - Diffusion in a two-dimensional channel with curved midline and varying width: reduction to an effective one-dimensional description. AB - Diffusion in a narrow two-dimensional channel with a midline that need not be straight and a width that may vary is reduced to an effective one-dimensional equation of motion. This equation takes the form of the Fick-Jacobs equation with a spatially varying effective diffusivity. The effective diffusivity includes a contribution that comes from the slope of the midline as well as the usual term stemming from variations in the channel width along the length of the channel. Our derivation of our equation of motion is completely rigorous and is based on an asymptotic expansion in a small dimensionless parameter that characterizes the channel width. For a channel that has a straight midline or wall, our equation of motion reduces to Zwanzig's equation [R. Zwanzig, J. Phys. Chem. 96, 3926 (1992)]. Our derivation therefore provides a rigorous proof of the validity of the latter equation. Finally, the equation of motion is solved analytically for channels with curved midline and constant width. PMID- 20365154 TI - Critical Casimir effect in classical binary liquid mixtures. AB - If a fluctuating medium is confined, the ensuing perturbation of its fluctuation spectrum generates Casimir-like effective forces acting on its confining surfaces. Near a continuous phase transition of such a medium the corresponding order parameter fluctuations occur on all length scales and therefore close to the critical point this effect acquires a universal character, i.e., to a large extent it is independent of the microscopic details of the actual system. Accordingly it can be calculated theoretically by studying suitable representative model systems. We report on the direct measurement of critical Casimir forces by total internal reflection microscopy with femtonewton resolution. The corresponding potentials are determined for individual colloidal particles floating above a substrate under the action of the critical thermal noise in the solvent medium, constituted by a binary liquid mixture of water and 2,6-lutidine near its lower consolute point. Depending on the relative adsorption preferences of the colloid and substrate surfaces with respect to the two components of the binary liquid mixture, we observe that, upon approaching the critical point of the solvent, attractive or repulsive forces emerge and supersede those prevailing away from it. Based on the knowledge of the critical Casimir forces acting in film geometries within the Ising universality class and with equal or opposing boundary conditions, we provide the corresponding theoretical predictions for the sphere-planar wall geometry of the experiment. The experimental data for the effective potential can be interpreted consistently in terms of these predictions and a remarkable quantitative agreement is observed. PMID- 20365155 TI - Microscopic study and modeling of thermodiffusion in binary associating mixtures. AB - Thermodiffusion in associating mixtures is a complex phenomenon, owing to the strong dependence of the molecular structure of such mixtures on concentration. In this paper, we attempt to elucidate this phenomenon and propose a qualitative mechanism for the separation of species in binary associating mixtures. A correlation between the sign change in the thermal diffusion factor and a change in the molecular structure, mixture viscosity, and the excess entropy of mixing in such mixtures is established. To quantify this correlation, we modify our recently developed dynamic model based on the Drickamer nonequilibrium thermodynamic approach [M. Eslamian and M. Z. Saghir, Phys. Rev. E 80, 011201 (2009)] and propose expressions for the estimation of thermal diffusion factor in binary associating mixtures. The prediction power of the proposed expressions, as well as other widely used models, are examined against the experimental data. The proposed theoretical expressions are self-contained and only rely on the viscosity data as input and predict a sign change in the thermal diffusion factor in associating mixtures. PMID- 20365156 TI - Thermal conductivity of the Lennard-Jones chain fluid model. AB - Nonequilibrium molecular dynamics simulations have been performed to estimate, analyze, and correlate the thermal conductivity of a fluid composed of short Lennard-Jones chains (up to 16 segments) over a large range of thermodynamic conditions. It is shown that the dilute gas contribution to the thermal conductivity decreases when the chain length increases for a given temperature. In dense states, simulation results indicate that the residual thermal conductivity of the monomer increases strongly with density, but is weakly dependent on the temperature. Compared to the monomer value, it has been noted that the residual thermal conductivity of the chain was slightly decreasing with its length. Using these results, an empirical relation, including a contribution due to the critical enhancement, is proposed to provide an accurate estimation of the thermal conductivity of the Lennard-Jones chain fluid model (up to 16 segments) over the domain 0.816, we observe an increase in the period and random splittings of the trajectories caused by bifurcations in configuration space. We argue that the ratio of the splitting and contraction rates in large systems will determine the distribution of MS-packing geometrical families visited in steady state. This work is part of our long-term research program to develop a master-equation formalism to describe macroscopic slowly driven granular systems in terms of collections of small subsystems. PMID- 20365165 TI - Experimental demonstration of nonuniform frequency distributions of granular packings. AB - We developed an experimental method to generate mechanically stable (MS) packings of frictionless disks and performed coordinated experiments and simulations to characterize MS packings in small systems. For a given system geometry, MS packings occur as discrete, well-separated points in configuration space with probabilities that vary by many orders of magnitude and are robust with respect to the packing preparation. Over a continuous range of system geometries, MS packings occur as distinct geometrical families and only a small fraction of families are sampled via quasistatic dynamics. These results suggest that the most frequent MS packings may dominate the structural and mechanical properties of dense granular media. PMID- 20365166 TI - Unusual diffusion in a quasi-two-dimensional granular gas. AB - We have studied diffusion in a quasi-two-dimensional granular gas composed of plastic balls confined in a vertically vibrating thin box. The horizontal motion of the balls in the box is found to follow the Langevin equation with the top and bottom of the box acting on the balls with a viscous drag like that in a fluid. Surprisingly, we find that both the granular temperature and the diffusion constant increase with the number of balls (N) in the box for small N . The unusual diffusion can be explained by a two-state model, in which a ball is in contact with two effective temperature baths due to collisions with the top or bottom of the box and collisions with other balls. PMID- 20365167 TI - Horizontal segregation in a vertically vibrated binary granular system. AB - We present numerical simulations and experiments on the horizontal transport and segregation of binary granular mixtures with different sizes and/or different densities in a vertically vibrated container with a sawtooth-shaped base. The larger particles migrate to the positive or negative end of the container, depending on the ratios of the diameters and the densities of two kinds of particles, the vibrating frequencies, and the accelerations. In particular, horizontal segregation occurred even if all the particles have the same size but different densities. PMID- 20365168 TI - Jammed frictionless disks: Connecting local and global response. AB - By calculating the linear response of packings of soft frictionless disks to quasistatic external perturbations, we investigate the critical scaling behavior of their elastic properties and nonaffine deformations as a function of the distance to jamming. Averaged over an ensemble of similar packings, these systems are well described by elasticity, while in single packings we determine a diverging length scale l* up to which the response of the system is dominated by the local packing disorder. This length scale, which we observe directly, diverges as 1/Deltaz , where Deltaz is the difference between contact number and its isostatic value, and appears to scale identically to the length scale which had been introduced earlier in the interpretation of the spectrum of vibrational modes. It governs the crossover from isostatic behavior at the small scale to continuum behavior at the large scale; indeed we identify this length scale with the coarse graining length needed to obtain a smooth stress field. We characterize the nonaffine displacements of the particles using the displacement angle distribution, a local measure for the amount of relative sliding, and analyze the connection between local relative displacements and the elastic moduli. PMID- 20365169 TI - Morphological models of complex ordered materials based on inhomogeneously clipped Gaussian fields. AB - Clipping a Gaussian random field at a level that is position-dependent yields statistically inhomogeneous morphologies, relevant to many ordered nanostructured materials. The one-point and two-point probability functions of the morphology are derived, as well as a general relation between the specific surface area and the gradient of the clipping function. The general results are particularized for the comprehensive analysis of small-angle x-ray scattering and nitrogen adsorption of SBA-15 ordered mesoporous silica. PMID- 20365170 TI - Direct numerical simulations for non-Newtonian rheology of concentrated particle dispersions. AB - The non-Newtonian behavior of a monodisperse concentrated dispersion of spherical particles was investigated using a direct numerical simulation method, which takes into account hydrodynamic interactions and thermal fluctuations accurately. Simulations were performed under steady shear flow with periodic boundary conditions in the three directions. The apparent shear viscosity of the dispersions was calculated at volume fractions ranging from 0.31 to 0.56. Shear thinning behavior was clearly observed at high volume fractions. The low- and high-limiting viscosities were then estimated from the apparent viscosity by fitting these data into a semiempirical formula. Furthermore, the short-time motions were examined for Brownian particles fluctuating in concentrated dispersions, for which the fluid inertia plays an important role. The mean square displacement was monitored in the vorticity direction at several different Peclet numbers and volume fractions so that the particle diffusion coefficient is determined from the long-time behavior of the mean square displacement. Finally, the relationship between the non-Newtonian viscosity of the dispersions and the structural relaxation of the dispersed Brownian particles is examined. PMID- 20365171 TI - Influence of confinement by smooth and rough walls on particle dynamics in dense hard-sphere suspensions. AB - We used video microscopy and particle tracking to study the dynamics of confined hard-sphere suspensions. Our fluids consisted of 1.1-microm-diameter silica spheres suspended at volume fractions of 0.33-0.42 in water-dimethyl sulfoxide. Suspensions were confined in a quasiparallel geometry between two glass surfaces: a millimeter-sized rough sphere and a smooth flat wall. First, as the separation distance (H) is decreased from 18 to 1 particle diameter, a transition takes place from a subdiffusive behavior (as in bulk) at large H, to completely caged particle dynamics at small H. These changes are accompanied by a strong decrease in the amplitude of the mean-square displacement (MSD) in the horizontal plane parallel to the confining surfaces. In contrast, the global volume fraction essentially remains constant when H is decreased. Second, measuring the MSD as a function of distance from the confining walls, we found that the MSD is not spatially uniform but smaller close to the walls. This effect is the strongest near the smooth wall where layering takes place. Although confinement also induces local variations in volume fraction, the spatial variations in MSD can be attributed only partially to this effect. The changes in MSD are predominantly a direct effect of the confining surfaces. Hence, both the wall roughness and the separation distance (H) influence the dynamics in confined geometries. PMID- 20365172 TI - Liquid-to-solid transition of concentrated suspensions under complex transient shear histories. AB - Suspensions containing noncolloidal aluminum particles in a Newtonian carrier liquid and the effects of shear history on the rheological properties of suspensions are investigated showing a critical concentration phi(c), which is close to the "freezing" packing fraction of spherical particle suspensions. An apparent liquid-to-solid transition was clearly found for suspensions below phi(c) via transient step shear after long shear history as well as via the large amplitude oscillatory shear flow with controlled shear stress. The microstructures or the local flow characteristics of suspensions with phiphi(c) are still different according to the Fourier Transform Rheological analysis. Although suspensions with phiphi(c) disappears after preshear. PMID- 20365173 TI - Central role of thermal collective strain in the relaxation of structure in a supercooled liquid. AB - The spatial distribution of structural relaxation in a supercooled liquid is studied using molecular dynamics simulations of a two-dimensional binary mixture. It is shown that the spatial heterogeneity of the relaxation along with the time scale of the relaxation is determined, not by the frequency with which particles move a distance pi/2kBragg, but by the frequency with which particles can achieve persistent displacements. We show that these persistent displacements are achieved through the coupled action of local reorganizations and unrecoverable thermal strains. PMID- 20365174 TI - Mode-coupling behavior of a Lennard-Jones binary mixture upon increasing confinement. AB - Molecular dynamics simulations are performed on a Lennard Jones binary mixture confined in off lattice matrices of soft spheres with increasing radius. We focus on dynamics upon supercooling and in particular on testing the mode coupling theory properties of the confined mixture. Parameters of mode coupling theory in going from bulk to weak confinement, and from weak to strong confinement are extracted from simulations and analyzed. We focus on the study of the behavior of the single particle density correlators. We find that the mode coupling theory retains its validity also in the case of strong confinement, with a reduction of range of validity. The role of hopping is discussed in relation with the differences between the results obtained from the diffusion coefficients and the mode coupling theory predictions. PMID- 20365175 TI - Dynamical surface affinity of diphasic liquids as a probe of wettability of multimodal porous media. AB - We introduce a method for estimating the wettability of rock/oil/brine systems using noninvasive in situ nuclear magnetic relaxation dispersion. This technique scans over a large range of applied magnetic fields and yields unique information about the extent to which a fluid is dynamically correlated with a solid rock surface. Unlike conventional transverse relaxation studies, this approach is a direct probe of the dynamical surface affinity of fluids. To quantify these features we introduce a microscopic dynamical surface affinity index which measures the dynamical correlation (i.e., the microscopic wettability) between the diffusive fluid and the fixed paramagnetic relaxation sources at the pore surfaces. We apply this method to carbonate reservoir rocks which are known to hold about two thirds of the world's oil reserves. Although this nondestructive method concerns here an application to rocks, it could be generalized as an in situ liquid/surface affinity indicator for any multimodal porous medium including porous biological media. PMID- 20365176 TI - Changing growth conditions during surface growth. AB - Motivated by a series of experiments that revealed a temperature dependence of the dynamic scaling regime of growing surfaces, we investigate theoretically how a nonequilibrium growth process reacts to a sudden change of system parameters. We discuss quenches between correlated regimes through exact expressions derived from the stochastic Edwards-Wilkinson equation with a variable diffusion constant. Our study reveals that a sudden change of the diffusion constant leads to remarkable changes in the surface roughness. Different dynamic regimes, characterized by a power-law or by an exponential relaxation, are identified, and a dynamic phase diagram is constructed. We conclude that growth processes provide one of the rare instances where quenches between correlated regimes yield a power law relaxation. PMID- 20365177 TI - Modeling growth of one-dimensional islands: influence of reactive defects. AB - Influence of reactive defects on size distribution of one-dimensional islands is studied by means of kinetic Monte Carlo simulations in combination with an analytical approach. Two different models are examined: a model with anisotropically diffusing atoms irreversibly aggregating to islands, and a reversible model close to thermal equilibrium which allows atom detachment from islands during the growth. The models can be used to simulate island growth of group III metals deposited on the Si(100)2 x 1 surface at room temperature: Al, Ga (irreversible model), and In (equilibrium model). We demonstrate that concentration of the reactive defects 0.0025 per site may change the island size distribution from monomodal to monotonically decreasing in the case of the irreversible model. At concentration >or=0.005 defects per site, a difference between results of the studied models is suppressed by the influence of the defects and similar island size distributions are obtained. PMID- 20365178 TI - Development of an atomic-force-microscope-based hanging-fiber rheometer for interfacial microrheology. AB - A new interfacial microrheology technique using atomic force microscope (AFM) as a force sensor is developed. The probe used for microrheology contains a long vertical glass fiber with one end glued onto a rectangular shaped cantilever beam and the other end immersed through a water-air interface. The motion of the modified cantilever can be accurately described by the Langevin equation for a damped harmonic oscillator, from which we obtain the friction coefficient xi of the glass fiber in contact with the water. It is found that xi contains two contributions. One is generated by the bulk fluid, which increases with the immersion length of the glass fiber. The other contribution comes from the contact line between the water-air interface and the glass fiber, which is obtained by an extrapolation of the measured xi at the limit of zero immersion length. The experiment thus demonstrates an application of AFM in the studies of interfacial microrheology and contact line dynamics. PMID- 20365179 TI - Rotational dissipation and the Miesowicz coefficients. AB - In this work, we will study the relative contribution of each of the two dissipative channels of the Eriksen, Leslie, and Parodi (ELP) approach to the observed values of the Miesowicz viscosity coefficients of the nematic liquid crystals. According to the fundamental equation of the liquid crystal's viscosity dissipative process, TS=-integral d3r(sigma)ijA(ij)+hxN , there are two channels by which the nematic viscous dissipation can occur: or it occurs by means of a shear flow configuration, where A(ij) is the characterizing term, or it occurs by means of a rotational configuration, where N is the characterizing term (these parameters will be defined in the paper). It will be also shown that this relative contribution can be measured by a simple relationship connecting the Miesowicz coefficients, which exhibits a quasitemperature independent behavior, suggesting that it is nearly constant through the entire domain of the nematic phase. PMID- 20365180 TI - Liquid crystalline and antinematic behavior of shape-persistent macrocycles from molecular-dynamics simulations. AB - In this work we present a molecular-dynamics study of a coarse-grained (CG) model for a system of planar shape-persistent macrocycles (SPMs). SPMs are synthetic organic rigid macromolecules typically comprised of meta- and para-aromatics groups connected by acetylene and/or diacetylene units. In the CG model, each SPM is represented as a rigid hexagonal arrangement of 24 soft-repulsive spheres, resembling a large ring or hoop. The supramolecular arrangement of these macrocycles at high pressures is studied using N-P-T molecular-dynamics simulation both by expansion of an initial hexagonal lattice structure and also by compression of an isotropic phase. In both cases, systems under consideration exhibit an isotropic-smectic-A phase transition, which is detected by monitoring relevant order parameters and analyzing snapshots of equilibrium configurations. The smectic-A phase is unique; although the molecules form layers, the system presents antinematic order where the orientation of the molecular axes is perpendicular to the direction of the layers themselves. Due to their planar geometry, the SPM molecules would be expected to form columnar or nematic phases. On the contrary, these phases seem suppressed by a novel smectic-A phase, formed by the mutual interpenetration of the cycles. These results are a unique example of how molecular nonconvexity can, by itself, induce mesomorphism in anisotropic systems. PMID- 20365181 TI - Dynamics of loop formation in a semiflexible polymer. AB - The dynamics of loop formation by linear polymer chains has been a topic of several theoretical and experimental studies. Formation of loops and their opening are key processes in many important biological processes. Loop formation in flexible chains has been extensively studied by many groups. However, in the more realistic case of semiflexible polymers, not much results are available. In a recent study [K. P. Santo and K. L. Sebastian, Phys. Rev. E 73, 031923 (2006)], we investigated opening dynamics of semiflexible loops in the short chain limit and presented results for opening rates as a function of the length of the chain. We presented an approximate model for a semiflexible polymer in the rod limit based on a semiclassical expansion of the bending energy of the chain. The model provided an easy way to describe the dynamics. In this paper, using this model, we investigate the reverse process, i.e., the loop formation dynamics of a semiflexible polymer chain by describing the process as a diffusion-controlled reaction. We make use of the "closure approximation" of Wilemski and Fixman [G. Wilemski and M. Fixman, J. Chem. Phys. 60, 878 (1974)], in which a sink function is used to represent the reaction. We perform a detailed multidimensional analysis of the problem and calculate closing times for a semiflexible chain. We show that for short chains, the loop formation time tau decreases with the contour length of the polymer. But for longer chains, it increases with length obeying a power law and so it has a minimum at an intermediate length. In terms of dimensionless variables, the closing time is found to be given by tau approximately Ln exp(const/L), where n=4.5-6. The minimum loop formation time occurs at a length Lm of about 2.2-2.4. These are, indeed, the results that are physically expected, but a multidimensional analysis leading to these results does not seem to exist in the literature so far. PMID- 20365182 TI - Simulation study of sulfonate cluster swelling in ionomers. AB - We have performed simulations to study how increasing humidity affects the structure of Nafion-like ionomers under conditions of low sulfonate concentration and low humidity. At the onset of membrane hydration, the clusters split into smaller parts. These subsequently swell, but then maintain constant the number of sulfonates per cluster. We find that the distribution of water in low-sulfonate membranes depends strongly on the sulfonate concentration. For a relatively low sulfonate concentration, nearly all the side-chain terminal groups are within cluster formations, and the average water loading per cluster matches the water content of membrane. However, for a relatively higher sulfonate concentration the water-to-sulfonate ratio becomes nonuniform. The clusters become wetter, while the intercluster bridges become drier. We note the formation of unusual shells of water-rich material that surround the sulfonate clusters. PMID- 20365183 TI - Response of shear stress to ac electric fields under steady shear flow in a droplet-dispersed phase. AB - We have measured the response of shear stress to ac electric fields under steady shear flow in the droplet-dispersed phase of an immiscible polymer blend. A characteristic mode was found under steady shear flow, the relaxation frequency of which increased with increasing the shear rate. In the frequency dispersion, a scaling relation derived from dimensional analysis was confirmed to hold. The origin of the mode was investigated on the basis of the Maffettone-Minale (MM) model, in which the droplet shape is described by a second-rank tensor. The frequency dispersion of the response was also calculated using a modified MM model. PMID- 20365184 TI - Stochastic model of self-assembly of cell-laden hydrogels. AB - Recent progress in bottom-up tissue engineering has demonstrated that three dimensional tissue constructs with predefined architectures may be obtained by assembling shape-controlled hydrogels in multiphase reactor systems. Driven by the hydrophobic force between gel unit and liquid media, highly ordered hydrogel clusters can be formed. Many complex factors occurring at microscale (i.e., gel unit collisions, hydrophobic forces, and gel unit movement) are involved in the self-assembly process. In this paper a two-dimensional off-lattice Monte Carlo model with Lennard-Jones-type potential describing unit-unit interactions is introduced for studying this process. Simulations are shown to agree well with the experimental results for hydrogel assembly in mineral oil. The simulation method is demonstrated for rectangular hydrogel units of different aspect ratios as well as extended to the case of more complex hydrogel unit geometries. PMID- 20365186 TI - Computer simulation of wound closure in epithelial tissues: cell-basal-lamina adhesion. AB - The mechanism of wound closure in epithelial tissues, i.e., cell monolayer sheets, is investigated through computer simulations. A wound means an area in which some cells have been removed from the normal tissue. The vertex dynamics cell model [T. Nagai and H. Honda, Philos. Mag. B 81, 699 (2001)], which describes morphogenesis of epithelial tissues using the concepts of statistical physics, is modified and applied to the closure of small wounds without mitosis. It is shown that cell-basal-lamina adhesion governs the wound closure competing with cell-cell adhesion and cell elasticity. The simulation results reproduce the actual wound closure process qualitatively and partly quantitatively. The closing proceeds with the translation of the edges of wound polygons toward the wound center and the intermittent reduction in the number of polygon edges. Over time, the process leads to an exponential decrease in the wound area. A shape factor is introduced to describe the wound shape quantitatively and is used to examine the time variation thereof. A method for determining model parameters by comparison with the experiments is given. PMID- 20365185 TI - Aggregation of chemotactic organisms in a differential flow. AB - We study the effect of advection on the aggregation and pattern formation in chemotactic systems described by Keller-Segel-type models. The evolution of small perturbations is studied analytically in the linear regime complemented by numerical simulations. We show that a uniform differential flow can significantly alter the spatial structure and dynamics of the chemotactic system. The flow leads to the formation of anisotropic aggregates that move following the direction of the flow, even when the chemotactic organisms are not directly advected by the flow. Sufficiently strong advection can stop the aggregation and coarsening process that is then restricted to the direction perpendicular to the flow. PMID- 20365187 TI - Base-pair opening and bubble transport in a DNA double helix induced by a protein molecule in a viscous medium. AB - The protein-DNA interaction dynamics is studied by modeling the DNA bases as classical spins in a coupled spin system, which are bosonized and coupled to thermal phonons and longitudinal motion of the protein molecule in the nonviscous limit. The nonlinear dynamics of this protein-DNA complex molecular system is governed by the completely integrable nonlinear Schrodinger (NLS) equation which admits N -soliton solutions. The soliton excitations of the DNA bases in the two strands make localized base-pair opening and travel along the DNA chain in the form of a bubble. This may characterize the bubble generated during the transcription process, when an RNA polymerase binds to a promoter site in the DNA double helical chain. When the protein-DNA molecular system interacts with the surrounding viscous solvating water medium, the dynamics is governed by a perturbed NLS equation. This equation is solved using a multiple scale perturbation analysis, by treating the viscous effect as a weak perturbation, and the results show that the viscosity of the solvent medium damps out the soliton as time progresses. PMID- 20365188 TI - Vesicles under simple shear flow: elucidating the role of relevant control parameters. AB - The dynamics of vesicles under shear flow are carefully analyzed in the regime of a small vesicle excess area relative to a sphere. This regime corresponds to the quasispherical limit, for which several groups have analytically extracted simple nonlinear differential equations. Under shear flow, vesicles are known to exhibit three types of motion: (i) tank-treading (TT): the vesicle assumes a steady inclination angle with respect to the flow direction, while its membrane undergoes a tank-treading motion, (ii) tumbling (TB), and (iii) vacillating breathing (VB): the vesicle main axis oscillates about the flow direction, whereas the overall shape undergoes a breathinglike motion. The region of existence for each regime depends on material and control parameters. The whole set of parameters can be cast into three dimensionless control parameters: (i) the viscosity ratio between the internal and external fluid, lambda , (ii) the excess area relative to a sphere (this parameter measures the degree of the vesicle deflation), Delta , and (iii) the capillary number (the ratio between the vesicle relaxation time toward its equilibrium shape after cessation of the flow and the flow time scale, which is the inverse shear rate), Ca. Recent studies [Danker, Phys. Rev. E 76, 041905 (2007)] have focused on the shape of the phase diagram (representing the TT, TB, and VB regimes in the Ca-lambda plane). In this paper, the physical quantities are analyzed in detail and attention is brought to features that are essential for future experimental studies. It is shown that the boundaries delimiting different dynamical regimes (TT, TB, and VB) in parameter space depend on the three dimensionless control parameters, in contrast with a recent study [V. V. Lebedev, Phys. Rev. Lett. 99, 218101 (2007)] where it is claimed that only two parameters are relevant. Consideration of the amplitude of oscillation (of the vesicle orientation angle and its shape deformation) in the VB mode reveals an even more significant dependence on the three parameters. It is also shown that the inclination angle in the TT regime significantly depends on the shear rate (Ca), which runs contrary to common belief. Finally, we show that the TB and VB periods are quite insensitive to Ca, in marked contrast with a recent study [H. Noguchi and G. Gompper, Phys. Rev. Lett. 98, 128103 (2007)]. PMID- 20365189 TI - Nonlinear breathing modes at a defect site in DNA. AB - Molecular-dynamics simulations of a normal DNA duplex show that breathing events typically occur on the microsecond time scale. This paper analyzes a 12 base pairs DNA duplex containing the "rogue" base difluorotoluene (F) in place of a thymine base (T), for which the breathing events occur on the nanosecond time scale. Starting from a nonlinear Klein-Gordon lattice model and adding noise and damping, we obtain a mesoscopic model of the DNA duplex close to that observed in experiments and all-atom molecular dynamics simulations. The mesoscopic model is calibrated to data from the all-atom molecular dynamics package AMBER for a variety of twist angles of the DNA duplex. Defects are considered in the interchain interactions as well as in the along-chain interactions. This paper also discusses the role of the fluctuation-dissipation relations in the derivation of reduced (mesoscopic) models, the differences between the potential of mean force and the potential energies used in Klein-Gordon lattices, and how breathing can be viewed as competition between the along-chain elastic energy and the interchain binding energy. PMID- 20365190 TI - Critical examination of the inherent-structure-landscape analysis of two-state folding proteins. AB - Recent studies attracted the attention on the inherent-structure-landscape (ISL) approach as a reduced description of proteins allowing to map their full thermodynamic properties. However, the analysis has been so far limited to a single topology of a two-state folding protein, and the simplifying assumptions of the method have not been examined. In this work, we construct the thermodynamics of four two-state folding proteins of different sizes and secondary structure by molecular dynamics (MD) simulations using the ISL method and critically examine possible limitations of the method. Our results show that the ISL approach correctly describes the thermodynamics function, such as the specific heat, on a qualitative level. Using both analytical and numerical methods, we show that some quantitative limitations cannot be overcome with enhanced sampling or the inclusion of harmonic corrections. PMID- 20365191 TI - Photonic crystal fiber in the polychaete worm Pherusa sp. AB - Setae of the polychaete worm Pherusa exhibit remarkably strong photonic effects, which arise from their two-dimensional-periodic internal structure of hexagonally packed cylindrical channels. The hexagonal order is limited to monocrystalline domains of different orientation, which results in an overall polycrystalline effect. A detailed experimental and theoretical investigation of this structure reveals that the internal photonic structure is carefully tuned with respect to its lattice constant in order to provide an optical response coinciding with the visible wavelength rage. A further optimization is observed for the packing fraction of cylindrical channels in order to maximize the width of photonic band gaps, and hence the reflectance of incident visible light. PMID- 20365192 TI - Length-dependent force characteristics of coiled coils. AB - Coiled-coil domains within and between proteins play important structural roles in biology. They consist of two or more alpha helices that form a superhelical structure due to packing of the hydrophobic residues that pattern each helix. A recent continuum model showed that the correspondence between the chirality of the pack to that of the underlying hydrophobic pattern comes about because of the internal deformation energy associated with each helix in forming the superhelix. We have developed a coarse-grained atomistic model for coiled coils that includes the competition between the hydrophobic energy that drives folding and the cost due to deforming each helix. The model exhibits a structural transition from a non-coiled-coil to coiled-coil state as the contribution from the deformation energy changes. Our model is able to reproduce naturally occurring coiled coils and essential features seen in unzipping experiments. We explore the force extension properties of these model coiled coils as a function helix length and find that shorter coils unfold at lower force than longer ones with the required unfolding force eventually becoming length independent. PMID- 20365193 TI - Maximum, minimum, and optimal mutation rates in dynamic environments. AB - We analyze the dynamics of the parallel mutation-selection quasispecies model with a changing environment. For an environment with the sharp-peak fitness function in which the most fit sequence changes by k spin flips every period T , we find analytical expressions for the minimum and maximum mutation rates for which a quasispecies can survive, valid in the limit of large sequence size. We find an asymptotic solution in which the quasispecies population changes periodically according to the periodic environmental change. In this state we compute the mutation rate that gives the optimal mean fitness over a period. We find that the optimal mutation rate per genome, k/T , is independent of genome size, a relationship which is observed across broad groups of real organisms. PMID- 20365194 TI - Disordered, stretched, and semiflexible biopolymers in two dimensions. AB - We study the effects of intrinsic sequence-dependent curvature for a two dimensional semiflexible biopolymer with short-range correlation in intrinsic curvatures. We show exactly that when not subjected to any external force, such a system is equivalent to a system with a well-defined intrinsic curvature and a proper renormalized persistence length. We find the exact expression for the distribution function of the equivalent system. However, we show that such an equivalent system does not always exist for the polymer subjected to an external force. We find that under an external force, the effect of sequence disorder depends upon the averaging order, the degree of disorder, and the experimental conditions, such as the boundary conditions. Furthermore, a short to moderate length biopolymer may be much softer or has a smaller apparent persistent length than what would be expected from the "equivalent system." Moreover, under a strong stretching force and for a long biopolymer, the sequence disorder is immaterial for elasticity. Finally, the effect of sequence disorder may depend upon the quantity considered. PMID- 20365195 TI - Elastic energy of protein-DNA chimeras. AB - We present experimental measurements of the equilibrium elastic energy of protein DNA chimeras, for two different sets of attachment points of the DNA "molecular spring" on the surface of the protein. Combining these with measurements of the enzyme's activity under stress and a mechanical model of the system, we determine how the elastic energy is partitioned between the DNA and the protein. The analysis shows that the protein is mechanically stiffer than the DNA spring. PMID- 20365196 TI - Finite-temperature local protein sequence alignment: percolation and free-energy distribution. AB - Sequence alignment is a tool in bioinformatics that is used to find homological relationships in large molecular databases. It can be mapped on the physical model of directed polymers in random media. We consider the finite-temperature version of local sequence alignment for proteins and study the transition between the linear phase and the biologically relevant logarithmic phase, where the free energy grows linearly or logarithmically with the sequence length. By means of numerical simulations and finite-size-scaling analysis, we determine the phase diagram in the plane that is spanned by the gap costs and the temperature. We use the most frequently used parameter set for protein alignment. The critical exponents that describe the parameter-driven transition are found to be explicitly temperature dependent. Furthermore, we study the shape of the (free-) energy distribution close to the transition by rare-event simulations down to probabilities on the order 10(-64). It is well known that in the logarithmic region, the optimal score distribution (T=0) is described by a modified Gumbel distribution. We confirm that this also applies for the free-energy distribution (T>0). However, in the linear phase, the distribution crosses over to a modified Gaussian distribution. PMID- 20365197 TI - Spontaneous brain activity as a source of ideal 1/f noise. AB - We study the electroencephalogram (EEG) of 30 closed-eye awake subjects with a technique of analysis recently proposed to detect punctual events signaling rapid transitions between different metastable states. After single-EEG-channel event detection, we study global properties of events simultaneously occurring among two or more electrodes termed coincidences. We convert the coincidences into a diffusion process with three distinct rules that can yield the same mu only in the case where the coincidences are driven by a renewal process. We establish that the time interval between two consecutive renewal events driving the coincidences has a waiting-time distribution with inverse power-law index mu approximately 2 corresponding to ideal 1/f noise. We argue that this discovery, shared by all subjects of our study, supports the conviction that 1/f noise is an optimal communication channel for complex networks as in art or language and may therefore be the channel through which the brain influences complex processes and is influenced by them. PMID- 20365198 TI - Effect of correlated lateral geniculate nucleus firing rates on predictions for monocular eye closure versus monocular retinal inactivation. AB - Monocular deprivation experiments can be used to distinguish between different ideas concerning properties of cortical synaptic plasticity. Monocular deprivation by lid suture causes a rapid disconnection of the deprived eye connected to cortical neurons whereas total inactivation of the deprived eye produces much less of an ocular dominance shift. In order to understand these results one needs to know how lid suture and retinal inactivation affect neurons in the lateral geniculate nucleus (LGN) that provide the cortical input. Recent experimental results by Linden showed that monocular lid suture and monocular inactivation do not change the mean firing rates of LGN neurons but that lid suture reduces correlations between adjacent neurons whereas monocular inactivation leads to correlated firing. These, somewhat surprising, results contradict assumptions that have been made to explain the outcomes of different monocular deprivation protocols. Based on these experimental results we modify our assumptions about inputs to cortex during different deprivation protocols and show their implications when combined with different cortical plasticity rules. Using theoretical analysis, random matrix theory and simulations we show that high levels of correlations reduce the ocular dominance shift in learning rules that depend on homosynaptic depression (i.e., Bienenstock-Cooper-Munro type rules), consistent with experimental results, but have the opposite effect in rules that depend on heterosynaptic depression (i.e., Hebbian/principal component analysis type rules). PMID- 20365199 TI - Maximum likelihood estimation of protein kinetic parameters under weak assumptions from unfolding force spectroscopy experiments. AB - Single molecule force spectroscopy (SMFS) is extensively used to characterize the mechanical unfolding behavior of individual protein domains under applied force by pulling chimeric polyproteins consisting of identical tandem repeats. Constant velocity unfolding SMFS data can be employed to reconstruct the protein unfolding energy landscape and kinetics. The methods applied so far require the specification of a single stretching force increase function, either theoretically derived or experimentally inferred, which must then be assumed to accurately describe the entirety of the experimental data. The very existence of a suitable optimal force model, even in the context of a single experimental data set, is still questioned. Herein, we propose a maximum likelihood (ML) framework for the estimation of protein kinetic parameters which can accommodate all the established theoretical force increase models. Our framework does not presuppose the existence of a single force characteristic function. Rather, it can be used with a heterogeneous set of functions, each describing the protein behavior in the stretching time range leading to one rupture event. We propose a simple way of constructing such a set of functions via piecewise linear approximation of the SMFS force vs time data and we prove the suitability of the approach both with synthetic data and experimentally. Additionally, when the spontaneous unfolding rate is the only unknown parameter, we find a correction factor that eliminates the bias of the ML estimator while also reducing its variance. Finally, we investigate which of several time-constrained experiment designs leads to better estimators. PMID- 20365200 TI - Adaptive self-organization in a realistic neural network model. AB - Information processing in complex systems is often found to be maximally efficient close to critical states associated with phase transitions. It is therefore conceivable that also neural information processing operates close to criticality. This is further supported by the observation of power-law distributions, which are a hallmark of phase transitions. An important open question is how neural networks could remain close to a critical point while undergoing a continual change in the course of development, adaptation, learning, and more. An influential contribution was made by Bornholdt and Rohlf, introducing a generic mechanism of robust self-organized criticality in adaptive networks. Here, we address the question whether this mechanism is relevant for real neural networks. We show in a realistic model that spike-time-dependent synaptic plasticity can self-organize neural networks robustly toward criticality. Our model reproduces several empirical observations and makes testable predictions on the distribution of synaptic strength, relating them to the critical state of the network. These results suggest that the interplay between dynamics and topology may be essential for neural information processing. PMID- 20365201 TI - Effect of hydrogen bond networks on the nucleation mechanism of protein folding. AB - We have recently developed a kinetic model for the nucleation mechanism of protein folding (NMPF) in terms of ternary nucleation by using the first passage time analysis. A protein was considered as a random heteropolymer consisting of hydrophobic, hydrophilic (some of which are negatively or positively ionizable), and neutral beads. The main idea of the NMPF model consisted of averaging the dihedral potential in which a selected residue is involved over all possible configurations of all neighboring residues along the protein chain. The combination of the average dihedral, effective pairwise (due to Lennard-Jones type and electrostatic interactions), and confining (due to the polymer connectivity constraint) potentials gives rise to an overall potential around the cluster that, as a function of the distance from the cluster center, has a double well shape. This allows one to evaluate the protein folding time. In the original NMPF model hydrogen bonding was not taken into account explicitly. To improve the NMPF model and make it more realistic, in this paper we modify our (previously developed) probabilistic hydrogen bond model and combine it with the former. Thus, a contribution due to the disruption of hydrogen bond networks around the interacting particles (cluster of native residues and residue in the protein unfolded part) appears in the overall potential field around a cluster. The modified model is applied to the folding of the same model proteins that were examined in the original model: a short protein consisting of 124 residues (roughly mimicking bovine pancreatic ribonuclease) and a long one consisting of 2500 residues (as a representative of large proteins with superlong polypeptide chains), at pH=8.3 , 7.3, and 6.3. The hydrogen bond contribution now plays a dominant role in the total potential field around the cluster (except for very short distances thereto where the repulsive energy tends to infinity). It is by an order of magnitude stronger for hydrophobic residues than for hydrophilic ones. The range of "residue-cluster" distances, at which the hydrogen bond effect exists, is twice as long for hydrophobic residues as for hydrophilic ones. PMID- 20365202 TI - Minimal model for synchronization induced by hydrodynamic interactions. AB - Motivated by the observed coordination of nearby beating cilia, we use a scale model experiment to show that hydrodynamic interactions can cause synchronization between rotating paddles driven at constant torque in a very viscous fluid. Synchronization is only observed when the shafts supporting the paddles have some flexibility. The phase difference in the synchronized state depends on the symmetry of the paddles. We use the method of regularized Stokeslets to model the paddles and find excellent agreement with the experimental observations. We also use a simple analytic theory based on far-field approximations to derive scaling laws for the synchronization time as a function of paddle separation. PMID- 20365203 TI - Pitchfork and Hopf bifurcation thresholds in stochastic equations with delayed feedback. AB - The bifurcation diagram of a model stochastic differential equation with delayed feedback is presented. We are motivated by recent research on stochastic effects in models of transcriptional gene regulation. We start from the normal form for a pitchfork bifurcation, and add multiplicative or parametric noise and linear delayed feedback. The latter is sufficient to originate a Hopf bifurcation in that region of parameters in which there is a sufficiently strong negative feedback. We find a sharp bifurcation in parameter space, and define the threshold as the point in which the stationary distribution function p(x) changes from a delta function at the trivial state x=0 to p(x) approximately x(alpha) at small x (with alpha=-1 exactly at threshold). We find that the bifurcation threshold is shifted by fluctuations relative to the deterministic limit by an amount that scales linearly with the noise intensity. Analytic calculations of the bifurcation threshold are also presented in the limit of small delay tau-->0 that compare quite favorably with the numerical solutions even for moderate values of tau . PMID- 20365204 TI - Effectiveness of the Kozachenko-Leonenko estimator for generalized entropic forms. AB - In this Brief Report we discuss the effectiveness of the Kozachenko-Leonenko entropy estimator when generalized to cope with entropic forms customarily applied to study systems evincing asymptotic scale invariance and dependence (either of linear or nonlinear kind). We show that when the variables are independently and identically distributed the estimator is only valuable along the whole domain if the data follow the uniform distribution, whereas for other distributions the estimator is only effectual in the limit of the Boltzmann-Gibbs Shanon entropic form. We also analyze the influence of the dependence (linear and nonlinear) between variables on the accuracy of the estimator between variables. As expected in the last case the estimator loses efficiency for the Boltzmann Gibbs-Shanon entropic form as well. PMID- 20365205 TI - Dispersionless motion in a periodically rocked periodic potential. AB - Recently, dispersionless (coherent) motion of (noninteracting) massive Brownian particles, at intermediate time scales, was reported in a sinusoidal potential with a constant tilt. The coherent motion persists for a finite length of time before the motion becomes diffusive. We show that such coherent motion can be obtained repeatedly by applying an external zero-mean square-wave drive of appropriate period and amplitude instead of a constant tilt. Thus, the cumulative duration of coherent motion of particles is prolonged. Moreover, by taking an appropriate combination of periods of the external field, one can postpone the beginning of the coherent motion and can even have coherent motion at a lower value of position dispersion than in the constant tilt case. PMID- 20365206 TI - Cooperative jump motions of jammed particles in a one-dimensional periodic potential. AB - Cooperative jump motions are studied for mutually interacting particles in a one dimensional periodic potential. The diffusion constant for the cooperative motion in systems including a small number of particles is numerically calculated and it is compared with theoretical estimates. We find that the size distribution of the cooperative jump motions obeys an exponential law in a large system. PMID- 20365207 TI - One-dimensional diffusion: validity of various expressions for jump rates. AB - The coverage dependence of the one-dimensional collective diffusion coefficient is analyzed by using the gradient expansion of the local density. The transition probabilities are written as an expansion of the probabilities of the occupation configurations. Since the detail balance principle determines only a part of the diffusion terms in the expansion, different functional relations are proposed for these terms. The diffusion coefficient is obtained for various choices of these relations. However, some of them seem to be not physically sound and the diffusion coefficient does not behave properly. The range of validity of various expressions for the jump rates is determined and phase diagrams are shown. Besides that, it is shown that the transition state theory guarantees physically suitable behavior of the coefficient of one-dimensional diffusion. PMID- 20365208 TI - Hierarchical mean-field model describing relaxation in a small-world network. AB - This Brief Report presents the hierarchical reaction-diffusion partial differential equations (PDE) system, which reproduces a mean-square displacement and a density relaxation process corresponding to the anomalous diffusion on a small-world network. These results are confirmed by the comparison with the known direct numerical simulations. PMID- 20365209 TI - Curvature and shape determination of growing bacteria. AB - Bacterial cells come in a variety of shapes, determined by the stress-bearing cell wall. Though many molecular details about the cell wall are known, our understanding of how a particular shape is produced during cell growth is at its infancy. Experiments on curved Escherichia coli grown in microtraps, and on naturally curved Caulobacter crescentus, reveal different modes of growth: one preserving arc length and the other preserving radius of curvature. We present a simple model for curved cell growth that relates these two growth modes to distinct but related growth rules--"hooplike growth" and "self-similar growth"- and discuss the implications for microscopic growth mechanisms. PMID- 20365210 TI - Contrasting methods for symbolic analysis of biological regulatory networks. AB - Symbolic dynamics offers a powerful technique to relate the structure and dynamics of complex networks. We contrast the predictions of two methods of symbolic dynamics for the analysis of monotonic networks suggested by models of genetic control systems. PMID- 20365211 TI - Comment on "Writhe formulas and antipodal points in plectonemic DNA configurations". AB - We point out that the disagreement between the paper by Neukirch and Starostin [S. Neukirch and E. L. Starostin, Phys. Rev. E 78, 041912 (2008)] and ours [J. Samuel, S. Sinha, and A. Ghosh, J. Phys.: Condens. Matter 18, S253 (2006)] is only apparent and stems from a difference in approach. Neukirch and Starostin are concerned with classical elasticity and individual curves while we focus on statistical averages over curves. PMID- 20365213 TI - Unusual mechanism for the short-range electron transfer within gold-alkanethiol ionic-liquid films of subnanometer thickness. AB - Exploiting nanoscopically tunable composite gold-alkanethiol-ionic liquid/ferrocene self-assembled systems with tunable electron transfer distance, we discovered in the case of thinner alkanethiol films a thermally activated electron transfer pattern totally controlled by the viscosity-related slow relaxation mode(s) of the ionic liquid acting as the reactant's fluctuating environment. This pattern manifested through the activation enthalpy and volume parameters that are identical to those for viscous flow was explained in terms of the extreme adiabatic mechanism with a vanishing Marcus barrier (via the exponential Franck-Condon-like term approaching unity). PMID- 20365214 TI - Model for non-Gaussian intraday stock returns. AB - Stock prices are known to exhibit non-Gaussian dynamics, and there is much interest in understanding the origin of this behavior. Here, we present a model that explains the shape and scaling of the distribution of intraday stock price fluctuations (called intraday returns) and verify the model using a large database for several stocks traded on the London Stock Exchange. We provide evidence that the return distribution for these stocks is non-Gaussian and similar in shape and that the distribution appears stable over intraday time scales. We explain these results by assuming the volatility of returns is constant intraday but varies over longer periods such that its inverse square follows a gamma distribution. This produces returns that are Student distributed for intraday time scales. The predicted results show excellent agreement with the data for all stocks in our study and over all regions of the return distribution. PMID- 20365215 TI - Models of electrolyte solutions from molecular descriptions: the example of NaCl solutions. AB - We present a method to derive implicit solvent models of electrolyte solutions from all-atom descriptions; providing analytical expressions of the thermodynamic and structural properties of the ions consistent with the underlying explicit solvent representation. Effective potentials between ions in solution are calculated to perform perturbation theory calculations, in order to derive the best possible description in terms of charged hard spheres. Applying this method to NaCl solutions yields excellent agreement with the all-atom model, provided ion association is taken into account. PMID- 20365216 TI - Global mean first-passage times of random walks on complex networks. AB - We present a general framework, applicable to a broad class of random walks on complex networks, which provides a rigorous lower bound for the mean first passage time of a random walker to a target site averaged over its starting position, the so-called global mean first-passage time (GMFPT). This bound is simply expressed in terms of the equilibrium distribution at the target and implies a minimal scaling of the GMFPT with the network size. We show that this minimal scaling, which can be arbitrarily slow, is realized under the simple condition that the random walk is transient at the target site and independently of the small-world, scale-free, or fractal properties of the network. Last, we put forward that the GMFPT to a specific target is not a representative property of the network since the target averaged GMFPT satisfies much more restrictive bounds. PMID- 20365217 TI - Nonlinear elasticity of the phase-field crystal model from the renormalization group. AB - The rotationally covariant renormalization group equations of motion for the density wave amplitudes in the phase field crystal model are shown to follow from a dynamical equation driven by an effective free energy density that we derive. We show that this free energy can be written purely as a function of the strain tensor and thence derive the corresponding equations governing the nonlinear elastic response. PMID- 20365218 TI - Wigner surmise for Hermitian and non-Hermitian chiral random matrices. AB - We use the idea of a Wigner surmise to compute approximate distributions of the first eigenvalue in chiral random matrix theory, for both real and complex eigenvalues. Testing against known results for zero and maximal non-Hermiticity in the microscopic large- N limit, we find an excellent agreement valid for a small number of exact zero eigenvalues. Compact expressions are derived for real eigenvalues in the orthogonal and symplectic classes and at intermediate non Hermiticity for the unitary and symplectic classes. Such individual Dirac eigenvalue distributions are a useful tool in lattice gauge theory, and we illustrate this by showing that our results can describe data from two-color quantum chromodynamics simulations with chemical potential in the symplectic class. PMID- 20365219 TI - Zero-refractoriness spirals in phase-coupled excitable media. AB - Effects of excitability and coupling strength on plane and spiral waves in two dimensional excitable lattices modeled by phase-coupled elements are investigated. The corresponding phase diagrams for stable plane waves and spiral waves are obtained by simulations. The parameters capable of supporting stable spiral waves are sorted out together with the spiral rotation frequencies. This discrete model corresponds to an excitable medium with zero refractoriness and in the continuum limit supports zero-core spiral waves. The associated wave propagating behaviors are also discussed analytically and verified. PMID- 20365220 TI - Dual-mode spiral vortices. AB - We show that spiral vortices in oscillatory systems can lose stability to secondary modes to form dual-mode spiral vortices. The secondary modes grow at the vortex core where the oscillation amplitude vanishes but are nonlinearly damped by the oscillatory mode away from the core. Gradients of the oscillation phase, induced by the hosted secondary mode, can lead to additional hosting events that culminate in periodic core oscillations or in a novel form of spatiotemporal chaos. The results of this study apply to physical, chemical, and biological systems that go through cusp-Hopf, fold-Hopf, and Hopf-Turing bifurcations. PMID- 20365221 TI - Partial time-delay coupling enlarges death island of coupled oscillators. AB - Coupling (or connection) in complex systems is of crucial importance in determining the system's dynamics and realizing certain system's functions. In this work, we propose a coupling form, partial time-delay coupling in coupled oscillator systems, in which some oscillators are time-delay coupled and the others remain instantaneously coupled, and study its impact on dynamics. We find that the partial time-delay coupling greatly enlarges the domain of oscillation death island in parameter space. In particular, the smaller the ratio p of time delay coupled oscillators, the larger death island is. For a sufficiently large system, a universal amplification scaling, R=p(-1)(0